Assessment of Potential Accumulation of Trifluoroacetate in Terminal Lakes.

Trifluoroacetate (TFA) is the anionic form of the shortest perfluorocarboxylic acid (PFCA) and is ubiquitous in the environment at concentrations that are typically much higher than those of other PFCAs. As a stable and nonvolatile anion, it is expected to accumulate in terminal lakes in endorheic basins. This research sampled eight terminal lakes in the Western United States to determine the degree to which TFA is concentrating in these lakes and compare the data to samples collected from three of these lakes 25 years ago. The first observation was that three of the six terminal lakes sampled had higher TFA concentrations than their input streams, while the last two lakes lacked surface water inputs at the sampling time. The TFA concentrations in Mono Lake effectively remained constant over 25 years despite the input stream concentrations increasing 6.5-fold. In contrast, Pyramid Lake concentrations increased approximately the expected amount based on a simplistic analysis of input flows and concentrations. An additional observation was that lakes in basins with agricultural activity appeared to have higher TFA concentrations, which suggests an agricultural input.

Mammalian toxicity of trifluoroacetate and assessment of human health risks due to environmental exposures.

While trifluoroacetic acid has limited technical uses, the highly water-soluble trifluoroacetate (TFA) is reported to be present in water bodies at low concentrations. Most of the TFA in the environment is discussed to arise from natural processes, but also with the contribution from decomposition of environmental chemicals. The presence of TFA may result in human exposures. For hazard and risk assessment, the mammalian toxicity of TFA and human exposures are reviewed to assess the margin of exposures (MoE). The potential of TFA to induce acute toxicity is very low and oral repeated dose studies in rats have identified the liver as the target organ with mild liver hypertrophy as the lead effect. Biomarker analyses indicate that TFA is a weak peroxisome proliferator in rats. TFA administered to rats did not induce adverse effects in an extended one-generation study and in a developmental toxicity study or induce genotoxic responses. Based on recent levels of TFA in water and diet, MoEs for human exposures to TFA are well above 100 and do not indicate health risks.

Increases in Trifluoroacetate Concentrations in Surface Waters over Two Decades.

Trifluoroacetate (TFA) is a persistent perfluorinated alkanoic acid anion that has many anthropogenic sources, with fluorocarbon refrigerants being a major one. After an initial burst of research in the late 1990s and early 2000s, research on this ubiquitous pollutant declined as atmospheric emissions of the precursor compounds grew rapidly. Thus, there is little contemporaneous information about the concentrations of TFA in the environment and how they have changed over time. This research determined the change in TFA concentrations in streams by resampling a transect that was originally sampled in 1998. The transect was designed to determine the regional distribution of TFA both upwind and downwind of major metropolitan areas in Northern California as well as a set of globally remote sites in Alaska. The results showed that TFA concentrations increased by an average of 6-fold over the intervening 23 years, which resulted in a median concentration of 180 ng/L (range 21.3-2790). The highest concentrations were found in streams immediately downwind of the San Francisco Bay Area, while substantially lower concentrations were found in the upwind, regionally remote, and globally remote sites. The C3 to C5 perfluorinated alkanoic acids were also investigated, but they were rarely detected with this methodology.

Insufficient evidence for the existence of natural trifluoroacetic acid.

Trifluoroacetic acid (TFA) is a persistent and mobile pollutant that is present ubiquitously in the environment. As a result of a few studies reporting its presence in pre-industrial samples and a purported unaccounted source, TFA is often claimed to exist naturally. Here, we examine the evidence for natural TFA by: (i) critically evaluating measurements of TFA in pre-industrial samples; (ii) examining the likelihood of TFA formation by hypothesized mechanisms; (iii) exploring other potential TFA sources to the deep ocean; and (iv) examining global budgets of TFA. We conclude that the presence of TFA in the deep ocean and lack of closed TFA budget is not sufficient evidence that TFA occurs naturally, especially without a reasonable mechanism of formation. We argue the paradigm of natural TFA should no longer be carried forward.

Residue analytical method for the determination of trifluoroacetic acid and difluoroacetic acid in plant matrices by capillary electrophoresis tandem mass spectrometry (CE-MS/MS).

In the past years, the technology for trace residue analysis of plant protection compounds in plant and animal matrices, soil, and water has gradually changed to meet changing regulatory demands. Generally, from the '70s to the '90s of the last century, the active compounds and only a few major metabolites had to be determined in a typical "residue definition". Step by step and within the framework of product safety assessments of the enforcement of residues in dietary matrices and in the environment, further metabolites have come into the authorities focus. Many active substances were formerly determined via gas chromatography (GC) based detection techniques. The introduction of liquid chromatography tandem mass spectrometry (LC-MS/MS) technology in the '90s and the acceptance of this technique, by official bodies at the end of the '90s, has led to a major change for residue analytical laboratories all over the world. Most of the medium to non-polar active compounds as well as many of the more polar metabolites can be detected with this technique, and today LC-MS/MS is the "workhorse" in many residue analytical laboratories in the industry as well as official enforcement labs responsible for analyzing registration-related field studies. With the demand to analyze further breakdown products, more and more polar compounds, or even (permanently) charged target compounds, have now come into the focus of the registration authorities. This now brings standard LC-based techniques to their limits and requires the application of approaches such as hydrophilic interaction chromatography (HILIC) MS/MS or ion chromatography, however these techniques often incur related uncertainties and problems with matrix samples. The aim of this study was to develop a new CE-MS/MS-based approach to reduce the impact of matrix on the separation and detection of trifluoroacetic acid (TFA) and difluoroacetic acid (DFA) in agrochemical field trials. This project used 7 representative examples of fruit, grain and vegetables which had undergone homogenization and extraction with acetonitrile water and filtration before CE-MS/MS analysis. The CE-MS/MS developed reached the limit of quantitation (LOQ) requirement of current legislation for both TFA and DFA (0.01 mg/kg) in all 7 matrices tested. The mean relative standard deviation (RSD) obtained from the repeat analysis of control field trail samples in all matrices, for both TFA and DFA, was less than 10% meeting GLP guidelines. When compared with LC-MS/MS, using on column loading amounts, the CE-MS/MS was 17 - 43 times more sensitive than a standard method and less matrix effects were observed. The developed method was validated under GLP conditions to provide a GLP-validated residue analytical method for the charged metabolites TFA and DFA in matrix samples from GLP field residue trials.

Ultrashort-chain perfluoroalkyl substance trifluoroacetate (TFA) in beer and tea - An unintended aqueous extraction.

Trifluoroacetate (TFA) is an ultrashort-chain perfluoroalkyl substance, which is ubiquitously present in the aqueous environment. Due to its high mobility, it accumulates in plant material. The study presented here shows for the first time that TFA is a widely spread contaminant in beer and tea / herbal infusions. In 104beer samples from 23countries, TFA was detected up to 51 µg/L with a median concentration of 6.1 µg/L. An indicative brewing test and a correlation approach with potassium (K) indicate that the main source of TFA in beer is most likely the applied malt. It could be proven that the impact of the applied water is negligible in terms of TFA, which was supported by the analysis of numerous tap water samples from different countries. The unintended extraction of TFA was also demonstrated for tea / herbal infusions with a median concentration of 2.4 µg/L.

Fluorochemicals biodegradation as a potential source of trifluoroacetic acid (TFA) to the environment.

The anthropogenic release of trifluoroacetic acid (TFA) into the environmental media is not limited to photochemical oxidation of CFC alternatives and industrial emissions. Biological degradation of some fluorochemicals is expected to be a potential TFA source. For the first time, we assess if the potential precursors [6:2 fluorotelomer alcohol (6:2 FTOH), 4:2 fluorotelomer alcohol (4:2 FTOH), acrinathrin, trifluralin, and 2-(trifluoromethyl)acrylic acid (TFMAA)] can be biologically degraded to TFA. Results show that 6:2 FTOH was terminally transformed to 5:3 polyfluorinated acid (5:3 FTCA; 12.5 mol%), perfluorohexanoic acid (PFHxA; 2.0 mol%), perfluoropentanoic acid (PFPeA; 1.6 mol%), perfluorobutyric acid (PFBA; 1.7 mol%), and TFA (2.3 mol%) by day 32 in the landfill soil microbial culture system. 4:2 FTOH could remove multiple -CF2 groups by microorganisms and produce PFPeA (2.6 mol%), PFBA (17.4 mol%), TFA (7.8 mol%). We also quantified the degradation products of TFMAA as PFBA (1.3 mol%) and TFA (6.3 mol%). Furthermore, we basically analyzed the biodegradation contribution of short-chain FTOH as raw material residuals in commercial products to the TFA burden in the environmental media. We estimate global emission of 3.9-47.3 tonnes of TFA in the period from 1961 to 2019, and project 3.8-46.4 tonnes to be emitted from 2020 to 2040 via the pathway of 4:2 and 6:2 FTOH biodegradation (0.6-7.1 and 0.6-7.0 tonnes in China, respectively). Direct evidence of the experiments indicates that biodegradation of fluorochemicals is an overlooked source of TFA and there are still some unspecified mechanisms of TFA production pathways.

Distribution characteristics of trifluoroacetic acid in the environments surrounding fluorochemical production plants in Jinan, China.

Trifluoroacetic acid (TFA) is a ubiquitous and extremely stable contaminant in the ambient environment and may be discharged during fluorochemical production processes. However, the impacts of fluorochemical production on surrounding areas have seldom been evaluated. We focused on Jinan, the capital of Shandong Province, China, and measured TFA levels in water, soil, and air samples. Our results showed that the average TFA concentrations in flowing water bodies were lower than those in landscape water bodies. The average TFA concentrations in soils were significantly higher than the background concentration. As for atmospheric TFA levels, the mean concentrations in the gas phase were higher than those in the particle phase, and average daytime levels were slightly higher than nighttime levels. In addition, the quotient method was used to assess the ecological risk of TFA in water in Jinan. The ratio of pollutant environmental concentration to predicted no-effect concentration (PEC/PNEC) for TFA was greater than 1, indicating that TFA does potentially damage the aquatic ecosystem of Jinan. Our findings suggest that TFA pollution around fluoride production plants is a serious problem and that actions are required to avoid exacerbating the local ecological and environmental risks of TFA.

Fate of 6:2 fluorotelomer sulfonic acid in pumpkin (Cucurbita maxima L.) based on hydroponic culture: Uptake, translocation and biotransformation.

6:2 fluorotelomer sulfonic acid (6:2 FTSA) is currently used as an alternative to perfluorooctanesulfonate (PFOS) and is widely detected in the environment. The uptake, translocation and biotransformation of 6:2 FTSA in pumpkin (Cucurbita maxima L.) were investigated by hydroponic exposure for the first time. The root concentration factor (RCF) of 6:2 FTSA was 2.6-24.2 times as high as those of perfluoroalkyl acids (PFAAs) of the same or much shorter carbon chain length, demonstrating much higher bioaccumulative ability of 6:2 FTSA in pumpkin roots. The translocation capability of 6:2 FTSA from root to shoot depended on its hydrophobicity. Six terminal perfluorocarboxylic acid (PFCA) metabolites, including perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), perfluorobutanoic acid (PFBA), perfluoropropionic acid (PFPrA) and trifluoroacetic acid (TFA) were found in pumpkin roots and shoots. PFHpA was the primary metabolite in roots, while PFBA was the major product in shoots. 1-aminobenzotriazole (ABT), a cytochromes P450 (CYPs) suicide inhibitor, could decrease the concentrations of PFCA products with dose-dependent relationships in pumpkin tissues, implying the role of CYP enzymes involved in plant biotransformation of 6:2 FTSA. This study indicated that the application of 6:2 FTSA can lead to the occurrence of PFCAs (C2-C7) in plants.

Optimization of extraction solvents, solid phase extraction and decoupling for quantitation of free isoprenoid diphosphates in Haematococcus pluvialis by liquid chromatography with tandem mass spectrometry.

Isoprenoid diphosphates are important precursors actively participating in many downstream metabolisms; they are often in modified forms, e.g., protein-coupled or esterified form. Therefore, in vivo level of free isoprenoid diphosphates is quite low, ˜0.07 nmol/g fresh weight in plants. In order to directly measure the isoprenoid diphosphate pool during stress-induced accumulation of astaxanthin in Haematococcus pluvialis, the present study optimized several pretreatment procedures to enrich free isoprenoid diphosphates for high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) detection. Specifically, different extraction solvents, e.g., water, methanol, chloroform, and mixture of water, methanol, and chloroform (1:1:1, V/V/V), and solid phase extraction (SPE) columns (OASIS@ WAX and HLB Cartridges) were compared; and gentle decoupling by NaOH or trifluoroacetic acid (TFA) was introduced to release free isoprenoid diphosphates. Results found that solvent mixture of water, methanol and chloroform (1:1:1, V/V/V) showed the highest extraction efficiency (RE) for five isoprenoid diphosphates, ranging from 76.83% to 92.43%; HLB column showed the balanced recoveries ranging from 75.29% to 87.54%; and incubation with low NaOH (˜4.7 mmol/L) at 4 °C significantly increased detectable isoprenoid diphosphates in algal cells, some of which were undetectable or in trace level before NaOH decoupling. The method was applied to H. pluvialis cells under various stresses. Low levels of isoprenoid diphosphates were determined in most of the stresses used, e.g., 0.19 ± 0.09 to 0.98 ± 0.06 mg/g fresh weight (FW) for IPP/DMAPP, 0.35 ± 0.07 mg/g FW for GGPP and undetectable for FPP and GPP; while isoprenoid diphosphates were significantly accumulated in the dark to 3.27 ± 0.05, 0.17 ± 0.09, 1.81 ± 0.16 and 0.58 ± 0.07 mg/g FW for IPP/DMAPP, GPP, FPP and GGPP, respectively. These results implied that isoprenoid diphosphates were exhausted by downstream carotenogenesis under stress. Our work emphasizes NaOH decoupling for exact quantitation of in vivo isoprenoid diphosphates.

Evidence for the Formation of Difluoroacetic Acid in Chlorofluorocarbon-Contaminated Ground Water.

The concentrations of difluoroacetic acid (DFA) and trifluoroacetic acid (TFA) in rainwater and surface water from Berlin, Germany resembled those reported for similar urban areas, and the TFA/DFA ratio in rainwater of 10:1 was in accordance with the literature. In contrast, nearby ground water historically contaminated with 1,1,2-trichloro-1,2,2-trifluoroethane (R113) displayed a TFA/DFA ratio of 1:3. This observation is discussed versus the inventory of microbial degradation products present in this ground water along with the parent R113 itself. A microbial transformation of chlorotrifluoroethylene (R1113) to DFA so far has not been reported for environmental media, and is suggested based on well-established mammalian metabolic pathways.

The contribution of fluoropolymer thermolysis to trifluoroacetic acid (TFA) in environmental media.

The source of trifluoroacetic acid (TFA) has long been a controversial issue. Fluoropolymer thermolysis is expected to be a potential anthropogenic source except for CFC alternatives. However, its TFA yield and contributions have rarely been reported more recently. In this study, we investigated the thermal properties of three kinds of fluoropolymers, including poly (vinylidene fluoride-co-hexafluropropylene) (PVDF-HFP), poly (vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) and poly (tetrafluoroethylene) (PTFE). A laboratory simulation experiment was then performed to analyze the TFA levels in the thermolysis products and hence to examine the TFA yields of these fluoropolymers. Thermolysis of these fluoropolymers occurred in the temperature ranges from ∼400 °C to ∼650 °C, with the peak weight loss rate at around 550-600 °C. TFA could be produced through fluoropolymer thermolysis when being heated to 500 °C and above. Average TFA yields of PTFE, PVDF-HFP and PVDF-CTFE were 1.2%, 0.9% and 0.3%, respectively. Furthermore, the contribution of fluoropolymer thermolysis and CFC alternatives to rainwater TFA in Beijing, China was evaluated by using a Two-Box model. The degradation of fluoropolymers and HCFCs/HFCs could explain 37.9-43.4 ng L-1 rainwater TFA in Beijing in 2014. The thermolysis of fluoropolymers contributed 0.6-6.1 ng L-1 of rainwater TFA, accounting for 1.6-14.0% of the TFA burden from all the precursors which were considered here.

Robust trace analysis of polar (C2-C8) perfluorinated carboxylic acids by liquid chromatography-tandem mass spectrometry: method development and application to surface water, groundwater and drinking water.

A simple and robust analytical method for the determination of perfluorinated carboxylic acids (PFCAs) with C2 to C8 chains, based on solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed, validated and applied to tap water, groundwater and surface water. Two stationary phases for LC (Obelisc N and Kinetex C18) and two materials with weak anion-exchange properties for SPE (Strata X-AW and Oasis WAX) were evaluated. Robust separation and retention was achieved with the reversed phase column and an acidic eluent. Quantitative extraction recoveries were generally achieved for PFCAs with C > 3, but extraction efficiencies were different for the two shortest chained analytes: 36 to 114% of perfluoropropanoate (PFPrA) and 14 to 99% of trifluoroacetate (TFA) were recovered with Strata X-AW, while 93 to 103% of PFPrA and 40 to 103% of TFA were recovered with Oasis WAX. The sample pH was identified as a key parameter in the extraction process. One-step elution-filtration was introduced in the workflow, in order to remove sorbent particles and minimise sample preparation steps. Validation resulted in limits of quantification for all PFCAs between 0.6 and 26 ng/L. Precision was between 0.7 and 15% and mean recoveries ranged from 83 to 107%. In groundwater samples from sites impacted by per- and polyfluoroalkyl substances (PFASs), PFCA concentrations ranged from 0.056 to 2.2 µg/L. TFA and perfluorooctanoate were the predominant analytes. TFA, however, revealed a more ubiquitous occurrence and was found in concentrations between 0.045 and 17 µg/L in drinking water, groundwater and surface water, which were not impacted by PFASs.

Purity assignment for peptide certified reference materials by combining qNMR and LC-MS/MS amino acid analysis results: application to angiotensin II.

The purity value assignment of metrologically traceable peptide reference standards requires specialized primary methods. Conventionally, amino acid analysis by isotope dilution tandem mass spectrometry (LC-MS/MS) following peptide hydrolysis is employed as a reference method. By contrast, quantitative nuclear magnetic resonance (qNMR) spectroscopy allows for quantitation of intact peptides, thus eliminating potential bias due to hydrolysis. Both methods are susceptible to interference from related peptide impurities, which need to be accurately measured and accounted for. The mass balance approach has also been employed for peptide purity measurements, whereby the purity is defined by the sum of the mass fraction of all impurities identified. Ideally, results from these three orthogonal methods can be combined for final purity assignment of peptide reference standards. Here we report a novel strategy for correcting both LC-MS/MS and 1H-qNMR results for related peptide impurities and combining results from both methods using a Bayesian statistical approach using mass balance results as prior knowledge. The mass balance method relied on a validated 19F-qNMR method to measure the trifluoroacetic acid (TFA) counter-ion, considered an impurity in this case at nearly 25% by mass. Using a candidate certified reference material (CRM) for angiotensin II, excellent agreement was achieved with the three methods. The final purity value assignment of the candidate CRM was 691 ± 9 mg/g (k = 2).

Sources, fates, toxicity, and risks of trifluoroacetic acid and its salts: Relevance to substances regulated under the Montreal and Kyoto Protocols.

Trifluoroacetic acid (TFA) is a breakdown product of several hydrochlorofluorocarbons (HCFC), regulated under the Montreal Protocol (MP), and hydrofluorocarbons (HFC) used mainly as refrigerants. Trifluoroacetic acid is (1) produced naturally and synthetically, (2) used in the chemical industry, and (3) a potential environmental breakdown product of a large number (>1 million) chemicals, including pharmaceuticals, pesticides, and polymers. The contribution of these chemicals to global amounts of TFA is uncertain, in contrast to that from HCFC and HFC regulated under the MP. TFA salts are stable in the environment and accumulate in terminal sinks such as playas, salt lakes, and oceans, where the only process for loss of water is evaporation. Total contribution to existing amounts of TFA in the oceans as a result of the continued use of HCFCs, HFCs, and hydrofluoroolefines (HFOs) up to 2050 is estimated to be a small fraction (<7.5%) of the approximately 0.2 µg acid equivalents/L estimated to be present at the start of the millennium. As an acid or as a salt TFA is low to moderately toxic to a range of organisms. Based on current projections of future use of HCFCs and HFCs, the amount of TFA formed in the troposphere from substances regulated under the MP is too small to be a risk to the health of humans and environment. However, the formation of TFA derived from degradation of HCFC and HFC warrants continued attention, in part because of a long environmental lifetime and due many other potential but highly uncertain sources.

Ion-pair reversed phase liquid chromatography with ultraviolet detection for analysis of ultraviolet transparent cations.

This paper describes the use of an anionic ion-pair reagent (IPR) to impove the ultraviolet (UV) detection and hydrophobic retention of polar and UV transparent cations. Anionic IPR added to the mobile phase forms an ion-pair with cations. Formation of the ion-pair causes a redshift in the absorption wavength, making it possible for direct UV detection of UV-inactive cations. The ion-pairs with increased hydrophobicity were separated by reversed phase liquid chromatography (RPLC). Different perfluorinated caboxylic acids (trifluoroacetic acid, heptafluorobutyric acid, nonafluoropentanoic acid) were evaluted as IPR in the separation and detection of the common cations sodium, ammonium and Tris(hydroxymethyl)aminomethane (Tris). The effects of the IPR type and concentration on separation and detection have been investigated to understand the separation and detection mechanisms. The optimal separation and detection condtions were attained with mobile phase containing 0.1% nonafluoropentanoic acid and with the UV detection at 210nm. UV detection and charged aerosol detection (CAD) were compared in the quantitation of the cations. The limit of quantitation (LOQ) of sodium and Tris with UV detection is comparable to that by CAD. The LOQ of ammonium with UV detection (1ppm or 3ng) is about 20-fold lower than that (20ppm or 60ng) by CAD. The RPLC-UV method was used to monitor ammonium clearance during ultrafiltration and diafiltration in the manfucaturing of biopharmceutical drug substance.

A novel HPLC-MS/MS method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.

Astemizole (AST), a second-generation antihistamine, is metabolized to desmethyl astemizole (DEA), and although it has been removed from the market for inducing QT interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. This report describes a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the concentrations of AST and DEA in beagle dog and cynomolgus monkey plasma with simple preparation method and short retention time. Prior to HPLC analyses, the plasma samples were extracted with simple liquid-liquid extraction method. The isocratic mobile phase was 0.025% trifluoroacetic acid (TFA dissolved in acetonitrile) and 20 mM ammonium acetate (94:6) at a flow rate of 0.25 mL/min and diphenhydramine used as internal standard. In MS/MS analyses, precursor ions of the analytes were optimized as protonated molecular ions: [M+H](+). The lower limit of quantification of astemizole was 2.5 ng/mL in both species and desmethyl astemizole were 7.5 ng/mL and 10 ng/mL in dog and monkey plasma, respectively. The accuracy, precision, and stability of the method were in accordance with FDA guidelines for the validation of bioanalytical methods. Finally this validated method was successfully applied to a pharmacokinetic study in dogs and monkeys after oral administration of 10 mg/kg AST.

A 17-fold increase of trifluoroacetic acid in landscape waters of Beijing, China during the last decade.

The concentrations of trifluoroacetic acid (TFA) were measured in urban landscape waters, tap water and snows in Beijing, China in 2012. Compared with the 2002 measurements, a 17-fold increase from 23-98ngL(-1) to 345-828ngL(-1) was observed for TFA concentrations in urban landscape waters, and an obvious increase from not detected (n.d.) to 155ngL(-1) occurred to TFA in tap water. By flux estimation between air and water interface, the remarkable increase of TFA was attributable to dry and wet deposition. The quantitative water-air-sediment interaction (QWASI) model simulated TFAs in various environmental media and showed that, over 99% of TFA distributed in water bodies. Our results recommend that measures are needed to control the increase of TFA in China.