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.

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.

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.

Effects of peptide fraction and counter ion on the development of clinical signs in experimental autoimmune encephalomyelitis.

The most commonly used immunogen to induce experimental autoimmune encephalomyelitis is MOG35-55 , a 21-residue peptide derived from myelin oligodendrocyte glycoprotein (MOG). In most studies, mice exhibit a chronic disease; however, in some studies mice show a transient disease. One variable that is not often controlled for is the peptide fraction of the purified MOG material, which can vary from less than 50% to over 90%, with the remainder of mass primarily comprised of the counter ion used for peptide purification. We compared the development of clinical signs in female C57Bl6 mice immunized with two commercially available MOG35-55 peptides of similar purity but different peptide fraction (MOG-A being 45%; MOG-B being 72%). A single immunization with MOG-A induced a chronic disease course with some recovery at later stages, whereas immunization with MOG-B induced a similar course of disease but with significantly lower average clinical scores despite a higher peptide content. The addition of a booster immunization significantly increased clinical severity with both preparations, and significantly reduced the average day of onset using MOG-A. To determine if the counter ion could influence disease, we compared MOG-B-containing trifluoroacetate with MOG-B-containing acetate. Although disease incidence and severity were similar, the average day of disease onset occurred approximately 5 days earlier with the use of MOG-B-containing trifluoroacetate. These results demonstrate that differences in peptide fraction influence the course of encephalomyelitis disease, which may be due in part to the levels of counter ions present in the purified material. These findings underscore the fact that a knowledge of peptide fraction is as critical as knowledge of peptide purity when using peptides from different sources.

Airborne trifluoroacetic acid and its fraction from the degradation of HFC-134a in Beijing, China.

Trifluoroacetic acid (TFA) has been attracting increasing attention worldwide because of its increased environmental concentrations and high aquatic toxicity. Atmospheric deposition is the major source of aquatic TFA, but only a few studies have reported either air concentrations or deposition fluxes for TFA. This is the first study to report the atmospheric concentrations of TFA in China, where an annular denuder and filter pack collection system were deployed at a highly urbanized site in Beijing. In total, 144 air samples were collected over the course of 1 year (from May 2012 to April 2013) and analyzed directly using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) or following derivatization by gas chromatography-mass spectrometry (GC-MS). The annual mean atmospheric concentration of TFA was 1580 ± 558 pg/m(3), higher than the previously reported annual mean levels in Germany and Canada. For the first time, it was demonstrated that maximum concentrations of TFA were frequently observed in the afternoon, following a diurnal cycle and suggesting that a major source of airborne TFA is likely degradation of volatile precursors. Using a deposition model, the annual TFA deposition flux was estimated to be 619 ± 264 µg m(-2) year(-1). Nevertheless, a box model estimated that the TFA deposition flux from the degradation of HFC-134a contributed only 14% (6-33%) to the total TFA deposition flux in Beijing. Source analysis is quite important for future TFA risk predictions; therefore, future research should focus on identifying additional sources.

A liquid chromatography method for determination of selected amino acids, coenzymes, growth regulators, and vitamins from Cicer arietinum (L.) and Solanum lycopersicum (L.).

A bottleneck in crosstalk and QC research has been the quantification of diverse chemotypes in small amounts of tissue. An LC-UV method for estimating 28 selected metabolites of the regulatory network underlying growth, development, maintenance, vital functions, defense reactions, and food quality is reported. The method was based on binary gradient resolutions of the analytes in an RP C18 column. The mobile phase comprised solvent A [water+0.1% trifluoroacetic acid (TFA)] and B (acetonitrile + 0.085% TFA at a flow rate of 1 ml/min. Twenty-three metabolites (selected amino acids, coenzymes, growth regulators, phenolic antioxidant, and water-soluble vitamins) were detected at 254 nm, and four fat-soluble vitamins at 280 nm. Jasmonic acid was quantified at 210 nm. The RSDs of peak area and retention time for each metabolite were <5.8%. The calibration graphs were linear with R2 values ranging from 0.98 to 0.99. The LODs (microg/mL) were about 0.01-1.0 for 23 metabolites quantified at 254 nm, 0.1-0.2 for fat-soluble vitamins, and 0.1 for jasmonic acid. The recoveries ranged from 80 to 105%, with RSDs of 2.8 to 11.2%. The method has been satisfactorily applied for determination of 28 metabolites from Cicer arietinum (L.) and Solanum lycopersicum (L.). It could be an alternative and competitive method of choice that can cheaply and easily perform routine analysis for food quality and targeted metabolomics of chickpea and tomato in response to stressors.

[Qualitative and quantitative analysis of fluoxetine hydrochloride by 19F NMR].

The chemical shift of fluoxetine hydrochloride appears at delta 14.15 in 19F NMR analysis. The delta moved upfield slightly from 14.158 to 14.145 when the concentration of solution became diluted from 2.00 to 0.05 mmol x L(-1). Spiking test was suggested to confirm the existence of the compound for qualitative analysis. 19F NMR detection sensitivity test illustrated that a concentration of 17 mg in 1 L water could be detected while the sample was scanned 500 times with optimum parameters. In quantitative analysis, standard curve of concentration versus fluorine signal intensity was proposed to determine the amount of fluoxetine. Long capillary tube containing trifluoroacetic acid was used as internal standard for the integration measurements and straight line was obtained with good fitting. Direct additions of trifluoroethanol to fluoxetine solutions gave a poorer standard curve.

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.

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.

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.

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.

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.

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.

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.