Comprehensive characterization of organic compounds in indoor dust after generic sample preparation with SUPRAS and analysis by LC-HRMS/MS.

In this study supramolecular solvents (SUPRAS) are employed for the first time to perform a wide screening of organic compounds in indoor dust samples. The potential of SUPRAS to efficiently extract a wide polarity range of compounds, and to simplify and improve the green properties of sample treatment in this area are discussed. SUPRAS made up of inverse aggregates of hexanol in tetrahydrofuran:water mixtures, which have been previously and successfully applied to the target determination of a variety of organic contaminants in different environmental matrices, were employed. Analysis was done with liquid chromatography and high resolution mass spectrometry. Twelve samples from public buildings (six educative buildings, two food stores, two nightclubs, one office and a coffee shop) were collected in South Spain. A total of 146 compounds were detected by target (∼33 %), suspect (∼55 %) and non-target screening (∼12 %). Around 86 % of all the compounds were identified (or tentatively identified) with levels of confidence equal or higher than 3. Novel designer drugs of abuse, unreported organophosphorus compounds and well-known organic contaminants, such as bisphenols, parabens, phthalates and flame retardants are reported. Differences with previous studies on wide screening of indoor dust reveal the influence of the employed databases for data processing and of the extraction method together with the different contamination profiles given by the sample location.

Determination of several PFAS groups in food packaging material from fast-food restaurants in France.

Per- and polyfluoroalkylated substances (PFAS) are a large group of toxic compounds which have been widely used in industrial and consumer applications, from where they can migrate into the environment. They can pose a risk to human health because they have been associated with several diseases. To obtain more information on the risk of PFAS in fast food packaging materials, several PFAS (perfluorocarboxylic acids or PFCAs (n = 16), perfluorosulfonic acids or PFSAs (n = 14), and a miscellaneous group constituted by sulfonamides (n = 5) and fluorotelomer phosphate esters or PAPs (n = 5)) were quantified in food contact materials (FCMs) from fast-food restaurants in France. Perfluorohexanoic acid (PFHxA), 6:2 fluorotelomer sulfonic acid (6:2 FTS) and 6:2/6:2 fluorotelomer phosphate diester (6:2/6:2 diPAP) were detected in all samples. PFCAs with shorter chain lengths (C4-C6) showed the highest concentrations compared to median (C7-C10) and longer chain length PFCAs (C11-C18). However, they had lower detection frequencies (DFs) (except for PFHxA, DF = 100%) with values of 36 and 34% for C4 and C5 PFCAs, respectively. The DF of longer chain length PFCAs was higher, especially those of the median chain length PFCAs (C8-C10, with DF = 79-98%). Analytes from the PFSA group with high DFs (70-98%) were perfluorobutane sulfonic acid (PFBS), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS, linear and branched) and 10:2 fluorotelomer sulfonic acid (10:2 FTS), with concentrations similar to some analytes from the PFCA group. 4:2 Fluorotelomer phosphate monoester (4:2 mPAP), 8:2 fluorotelomer phosphate monoester (8:2 mPAP) and 8:2/8:2 fluorotelomer phosphate diester (8:2/8:2 diPAP) were found with the highest concentrations (<0.006-42.7 ng g-1, <0.001-2.7 ng g-1 and <0.001-287 ng g-1, respectively) and the highest DFs (ranged 68-94%). Some correlations between analytes were found, indicating similar degradation routes or a common origin.

Supramolecular solvents for making comprehensive liquid-liquid microextraction in multiclass screening methods for drugs of abuse in urine based on liquid chromatography-high resolution mass spectrometry.

Multiclass screening methods involving hundreds of structurally unrelated compounds are becoming essential in many control labs and research areas. Accurate mass screening of a theoretically unlimited number of chemicals can be undertaken using liquid chromatography coupled to high resolution mass spectrometry (LCHRMS), but the lack of comprehensive sample treatments hinders this unlimited potential. In this research, the capability of supramolecular solvents (SUPRAS) for making comprehensive liquid-liquid microextraction (LLME) in multiclass screening methods based on LCHRMS was firstly explored. For this purpose, a SUPRAS made up of 1,2-hexanediol, sodium sulphate and water was synthesized directly in the urine and applied to compound extraction and interference removal in the screening of eighty prohibited substances in sports by LC-electrospray ionization-time of flight mass spectrometry. Selected substances included a wide range of polarities (log P from -2.4 to 9.2) and functionalities (e.g. alcohol, amine, amide, carboxyl, ether, ester, ketone, sulfonyl, etc.). No interfering peaks were observed for any of the 80 substances investigated. Around 84-93% of drugs were efficiently extracted (recoveries 70-120%) and 83-94% of the analytes did not show matrix effects (±20%) in the ten tested urines. Method detection limits for the drugs were in the interval 0.002-12.9 ng mL-1, which are in accordance with the Minimum Required Performance Levels values established by the World Anti-Doping Agency. The applicability of the method was evaluated by the screening of thirty-six blinded and anonymized urine samples, previously analyzed by gas or liquid chromatography-triple quadrupole. Seven of the samples lead to an adverse analytical finding in line with the results obtained by the conventional methods. This research proves that LLME based on SUPRAS constitutes an efficient, economic, and simple sample treatment in multiclass screening methods, an application that is unaffordable for conventional organic solvents.

Characterization of a new sustainable supramolecular solvent and application to the determination of oxy-PAHs in meat, seafood and fish tissues.

In this study we develop a green treatment method based on supramolecular solvents (SUPRASs) made up of reverse aggregates of short/medium chain length alcohols (C6-C10) in mixtures of water and a sustainable organic solvent (methyl-tetrahydrofuran). SUPRASs ingredients have low toxicity and can be obtained from renewable sources. The new SUPRASs were characterized and its suitability for determination of oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) in food was tested. Analysis was made by liquid chromatography coupled to high resolution mass spectrometry. The method provided quantification limits in the range 0.4-4 ng g-1 with low consumption of reagents (200uL of SUPRAS per sample) and it was based on simple agitation and centrifugation without concentration/evaporation steps. All target compounds (except 11-H-benzo[b]fluoren-11-one) were found in 7 out of 19 samples, mainly in fish and seafood samples, with levels in the range n.d. - 8 ng g-1.

Green nanostructured liquids for the analysis of urine in drug-facilitated sexual assault cases.

In this work, we optimize and validate a simple, time-saving, and environmentally friendly sample preparation method based on supramolecular solvents (SUPRAS), green nanostructured liquids, for the extraction of selected drug-facilitated sexual assault (DFSA) substances from human urine. The methodology was fast and simple (stirring, centrifugation, and dilution). Cubosomic SUPRAS were formed by the addition of 1,2-hexanediol (200 µL) to 1.0 mL of human urine containing 1 M Na2SO4. SUPRAS extracts were analyzed by LC-MS/MS. The method was fully validated for 23 DFSA compounds including 10 benzodiazepines, 1 z-hypnotic drug, 5 amphetamine derivatives, 3 cocaine metabolites, and 4 miscellaneous compounds. Extraction efficiency varied between 79 and 119%, and matrix effects were acceptable (-14.3/+21.5) for 87% of the compounds. Method detection and quantification limits ranged from 0.003 to 0.75 ng/mL and from 0.01 to 2.50 ng/mL, respectively. These values were low enough for the established minimum required performance limits (MRPL) of these substances. This simple and green method has a great potential to be implemented for the monitoring of illegal drugs involved in DFSA cases by forensic laboratories.

Cubosomic Supramolecular Solvents: Synthesis, Characterization, and Potential for High-Throughput Multiclass Testing of Banned Substances in Urine.

This paper was intended to efficiently extract multiclass prohibited substances in human sport drug testing by using supramolecular solvents (SUPRASs) made up of cubosomes. These SUPRASs, here first reported, are synthesized by the salt-induced coacervation of 1,2-hexanediol in urine. The formation of square and rounded cubosomes with a size range of 140-240 nm was confirmed by electron microscopy. These nanostructures consisted of 1,2-hexanediol, salt, and a high water content (36-61%, w/w). Their applicability in multiclass determinations was investigated by the extraction of 92 prohibited substances (log P from 2.4 to 9.2) belonging to the 10 categories of the World Anti-Doping Agency's (WADA) list. Variables influencing both recoveries and matrix effects were optimized. Cubosomic SUPRASs showed high extraction efficiency and interference removal capability, which was attributed to their large hydrophilicity and surface area. Both features were superior to those of the other 11 SUPRASs that were based on sponge droplets and inverted hexagonal aggregates and to those of conventional organic solvents. A sport drug-testing method based on cubosomic SUPRAS-LC-ESI-MS/MS was proposed and validated. Around 82-95% of drugs were efficiently extracted (recoveries 70-120%) in urine samples, and 81-92% did not present matrix effects. The method detection limits (0.001-4.2 ng mL-1) were all far below WADA's limits. The proposed SUPRAS-based sample treatment is as simple as QuEChERS, but the distinctive features of cubosomes confer them high capability in multiclass determinations.

Supramolecular solvent-based microextraction probe for fast detection of bisphenols by ambient mass spectrometry.

In this study, we investigated for the first time the suitability of supramolecular solvent (SUPRAS)-based microextraction probe for the development of generic and fast sample treatment prior to qualitative analysis by ambient mass spectrometry (AMS) based on ASAP (atmospheric solids analysis probe). SUPRAS are nanostructured liquids formed by the self-assembly of amphiphilic aggregates with multiple binding sites and microenvironments of different polarity for the efficient extraction of multiple compounds. Different types of SUPRAS were evaluated as a simple and single step sample treatment for ASAP. The method was applied to the screening of bisphenol A and structural analogues in thermal paper. Optimal results were achieved with SUPRAS synthesized with 1-decanol in mixtures of ethanol:water. SUPRAS (1.1-2 µL) were loaded onto glass probes and placed in contact with samples for 10 s before ASAP analysis. AMS signal peaks (width: 0.2-0.5 min) were easily integrated and normalized with internal standards (RSD: 2-25%). The method was applied to 62 samples of thermal paper. BPA and BPS were the most widely used, this highlighting the progressive industrial replacement of BPA by BPS.

A comprehensive study on the performance of different retention mechanisms in sport drug testing by liquid chromatography tandem mass spectrometry.

Anti-doping substances listed by the World Anti-Doping Agency (WADA) include hundreds of compounds of very different physico-chemical properties. Anti-doping control laboratories need to screen all these substances in the so-called Initial Testing Procedures (ITPs) what is very challenging from an analytical point of view. ITPs are mostly based on reversed-phase (RP) liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) using C18 columns, which feature poor retention and peak tailing for polar and basic compounds, respectively. While studies on this field dealing with the comparison of stationary phases are focused on certain chemical classes, this research provides a wide multi-target approach. For this purpose, a representative group of 93 anti-doping agents (log P from -2.4 to 9.2) included in ten different classes of prohibited substances was selected. A comprehensive study on the performance of six columns and four eluents on different separation parameters (retention factors, asymmetry factors, co-elutions, total run times) and matrix effects (signal enhancement or suppression) was performed for LC-MS/MS-based ITPs. Columns working in both RP [C18, C8, phenyl hexyl (PH), pentafluorophenyl (PFP) and mixed-mode hydrophilic/RP (HILIC-RP)) and hydrophilic (HILIC)] modes were investigated. Eluents contained methanol or acetonitrile as organic modifiers, with or without the addition of ammonium acetate. The best column-mobile phase binomial for ITPs was PFP using water-methanol (0.1% formic acid) as eluent, while HILIC was the best option for highly polar non-aromatic anti-doping agents, which were poorly addressed by PFP. Excellent good peak shapes and relative acceptable matrix interferences were obtained for HILIC-RP, which was tested for the first time for the analysis of anti-doping agents, although the number of compounds eluting too fast was too high. On the whole, the alkyl phase C18 showed the worst performance and although C8 and PH were better, their performance did not surpass that of PFP. Possible retention mechanisms underlying separation in the different stationary phases were discussed. This research provides valuable information to anti-doping control labs for improving LC-MS/MS-based ITPs and it proposes PFP as a suitable alternative to the already established C18.

Multi-class determination of intracellular and extracellular cyanotoxins in freshwater samples by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry.

In the past decades, the intensity and duration of cyanobacterial blooms are increasing due to anthropogenic factors. These phenomena worry drinking water companies and water managers because cyanobacteria produce a diverse range of cyanotoxins, which can cause liver, digestive and neurological diseases. The main exposure routes for humans are the consumption of drinking water that has not been effectively treated and the recreational use of polluted waters. For risk assessment and to conduct studies on large-scale occurrence, the development of reliable but simple, sensitive and cost-effective analytical approaches able to cover a wide range of cyanotoxins is essential. Additionally, the determination of intracellular and extracellular toxins separately is advantageous for risk management. To the best of our knowledge, this is the first time that a method for the multi-class determination of cyanotoxins in fresh water, which is able to separately report intra- and extracellular toxins, meet the criteria of simplicity (not requiring multiple sample preparation procedures or time-consuming steps) and it is based on highly specific high resolution mass spectrometry (potential for wide screening and retrospective analysis). Matrix effects, trueness and precision met general validation criteria for a group of nine cyanotoxins, including anatoxins, cylindrospermopsin and microcystins. Considering a 50 mL sample, the method quantification limits were within the range of 8-45 ng L-1 and 25-129 ng L-1 for intra- and extracellular cyanotoxins, respectively. Anatoxin-a, cylindrospermopsin and some microcystins were found in three out of four Dutch lakes included in the study, at concentrations up to 52 µg L-1.

A review on contaminants of emerging concern in European raptors (2002-2020).

Raptors (birds of prey and owls) have been widely used as suitable bioindicators of environmental pollution. They occupy the highest trophic positions in their food chains and are documented to bioaccumulate high concentrations of persistent pollutants such as toxic metals and legacy persistent organic pollutants (POPs).Whereas raptors played a critical role in developing awareness of and policy for chemical pollution, they have thus far played a much smaller role in current research on contaminants of emerging concern (CECs). Given the critical knowledge obtained from monitoring 'legacy contaminants' in raptors, more information on the levels and effects of CECs on raptors is urgently needed. This study critically reviews studies on raptors from Europe reporting the occurrence of CECs with focus on the investigated species, the sampled matrices, and the bioanalytical methods applied. Based on this, we aimed to identify future needs for monitoring CECs in Europe. Perfluoroalkyl substances (PFASs), novel flame retardants (NFRs), and to a lesser extent UV-filters, neonicotinoids, chlorinated paraffins, parabens and bisphenols have been reported in European raptors. White-tailed Eagle (Haliaeetus albicilla), Peregrine falcon (Falco peregrinus) and Northern goshawk (Accipiter gentilis) were the most frequently studied raptor species. Among matrices, eggs, feathers and plasma were the most widely employed, although the potential role of the preen gland as an excretory organ for CECs has recently been proposed. This review highlights the following research priorities for pollution research on raptors in Europe: 1) studies covering all the main classes of CECs; 2) research in other European regions (mainly East Europe); 3) identification of the most suitable matrices and species for the analysis of different CECs; and 4) the application of alternative sample treatment strategies (e.g. QuEChERS or pressurized liquid extraction) is still limited and conventional solvent-extraction is the preferred choice.

Supramolecular solvent-based high-throughput sample treatment for monitoring phytohormones in plant tissues.

Quantification of endogenous hormones in plants is essential to understand their growth, development and response to biotic and abiotic stresses. However, it is challenging to develop high-throughput sample treatments from complex plant tissues containing low amounts of structurally unrelated and labile phytohormones while delivering clean and analyte-enriched extracts. In this paper we propose the use of supramolecular solvents (SUPRASs) made up or inverted hexagonal nanostructures of alkanols to address this challenge. The strategy was applied, as a proof of concept, to the quantification of stress-related phytohormones belonging to different categories (abscisic acid, salicylic acid, jasmonic acid, methyl jasmonate and 3-indoleacetic acid) in melon and pepper leaves. Sample treatment consisted in a single extraction-cleanup step involving the use of a low volume of SUPRAS (244 µL), the stirring (5 min) and centrifugation (15 min) of the sample at room temperature, and the direct analysis of the extract by liquid chromatography tandem mass spectrometry (LC-MS/MS). This high-throughput sample treatment method delivered excellent results for the target phytohormones regarding absolute recoveries (80-92%), method quantification limits (0.05-2 ng g-1), reproducibility (1-7%) and matrix effects (+13 to -31%), in both melon and pepper leaves, compared to reported methods based on repetitive solvent extraction, purification and solvent evaporation steps. The method was successfully applied to determine target hormones in melon and pepper plants for the evaluation of the effect of thermal stress. It was found that their concentration increased in the ranges 1.2-1.9 and 1.3-3.8 times in melon and pepper leaves, respectively, compared with control samples.

Bioaccumulation potential of bisphenols and benzophenone UV filters: A multiresidue approach in raptor tissues.

Environmental exposure to bisphenols and benzophenone UV filters has received considerable attention due to the ubiquitous occurrence of these contaminants in the environment and their potential adverse health effects. The occurrence of bisphenols and benzophenone UV filters is well established in human populations, but data is scarce for wildlife, and especially for raptors (birds of prey, falcons and owls). In this study, concentrations of eight bisphenols and five benzophenone UV filters were determined in six raptor tissues, including muscle, kidney, liver, brain, preen gland (uropygial gland) and adipose. The tissue samples (n = 44) were taken from dead raptor species (1997-2011), including Eurasian sparrowhawks (Accipiter nisus, n = 2) and long-eared owls (Asio otus, n = 2), both from France, and white-tailed eagles (Haliaeetus albicilla, n = 16) from Greenland. Overall, six bisphenols and four benzophenone UV filters were found in the samples. Bisphenol A (BPA), bisphenol F (BPF), benzophenone-8 (BzP-8) and 4-hydroxybenzophenone (4-OH-BzP) were the most abundant contaminants, accounting for median concentrations of 67.5, 3.01, 27.1 and 9.70 ng/g wet weight (w.w.), respectively. The potential role of the preen gland as a major excretory organ for bisphenols and benzophenone UV filters was suggested since the median sum concentration of the two contaminant classes in the white-tailed eagle tissues showed higher bioaccumulation potential in the preen gland (5.86 ng/g w.w.) than the liver (2.92) and kidney (0.71). The concentrations of these contaminants in the tissues of the three raptor species indicated a pattern of increasing detection rates and median concentrations with an increase of the species size and their expected trophic position. To the best of our knowledge, this is the first peer-reviewed study to document multiresidues of both contaminant classes in raptor tissues.

Supramolecular solvent-based microextraction of aryl-phosphate flame retardants in indoor dust from houses and education buildings in Spain.

Aryl-phosphate flame retardants (aryl-OPFRs) are flame retardants or plasticizers (among other functions) that can be found in a wide variety of products, from furniture and textiles to cars and electronic equipment. There is an increasing concern about the human exposure to these contaminants due to their ubiquity (as additives they can be easily released from the product to the environment) and potential toxicity. In this study, we investigated the presence of six representative aryl-OPFRs, two well-known aryl-OPFRs (triphenyl phosphate, TPHP and 2-ethylhexyl diphenyl phosphate, EHDPP), two novel aryl-OPFRs (cresyl diphenyl phosphate, CDP and isodecyl diphenyl phosphate, IDPP) and two oligomeric aryl-OPFRs [bisphenol A bis(diphenyl phosphate), BDP and resorcinol bis(diphenyl phosphate, RDP] in indoor dust from houses and education buildings from Spain. Sample treatment was carried out by a novel and simple procedure based on supramolecular solvents (SUPRAS) prior to LC-MS/MS analysis. The median Σaryl-OPFRs was two times higher in classrooms than in houses, being particularly high at University classrooms. The most abundant aryl-OPFR in houses was TPHP (median 497 ng·g-1) while EHDPP (median 407 ng·g-1) and IDPP (median 403 ng·g-1) were dominant in classrooms. This is the first study reporting IDPP, BDP and RDP in different education buildings.

Tunable solvency mixtures of tetrahydrofuran:water for efficient and fast extraction/clean-up of trace contaminants.

In this study, we investigated the potential of mixtures of tetrahydrofuran (THF) and water as tunable solvents for the microextraction of contaminants in solid and in liquid matrices. These two miscible solvents have very different dielectric constant and Hildebrand solubility parameters, so that tunable mixtures spanning a wide range of dispersion and hydrogen bonding forces could be easily prepared by simply changing their composition. In this way, rapid and more efficient extraction methods can be developed. A liquid-liquid and a solid-liquid microextraction method for the determination of bisphenol A (BPA) in urine and ochratoxin A (OTA) in cereal baby food were developed as a proof of concept. Both, the chemical composition and the relative solvency of the THF-water mixtures, expressed as Teas solubility parameters, were studied in order to gain some insights into the chemical interactions governing analyte extraction. For urine, the salting-out extraction with THF:water and NaCl was evaluated, a process which is still scarcely investigated for analytical purposes. These methods featured good recoveries (above 95%), satisfactory standard deviation (5-6%) and good sensitivity (detection limits of 0.l µg L-1 for BPA and of 0.l ng g-1 for OTA) with the advantages of simplicity, rapidity and low consumption of reagents. Recoveries for other compounds and matrices (bisphenols ad phosphorus flame retardants in dust and in tap water, dyes in tap water and OTA in powder milk) were also assessed to prove the wide potential of these tunable solvent mixtures.

Multifunctional vesicular coacervates as engineered supramolecular solvents for wastewater treatment.

In this study, multifunctional supramolecular solvents (SUPRASs) able to simultaneously extract ionic, polar and hydrophobic organic compounds from wastewater have been developed. SUPRASs were synthesized in aqueous solutions containing mixtures of carboxylic acids and carboxylates that underwent spontaneous self-assembly and coacervation under the addition of tetraalkylammonium ions. These SUPRAS consisted of coacervate droplets made up of large unilamellar vesicular aggregates bridged by tetraalkylammonium ions. Both, the high kinetic stability of vesicles and their strong interaction with tetraalkylammonium ions through different bonds working cooperatively, made supramolecular nanostructures in the SUPRAS chemically stable, which minimized the presence of solvent residues in the treated water. The suitability of the synthesized SUPRASs to behave as multifunctional extractants in water treatment was investigated by their application to the removal of anionic, cationic and ionizable dyes and PAHs. All the variables affecting the extraction process were optimized (i.e. chain length of the tetraalkylammonium ion, fractional SUPRAS phase volume, pH, ionic strength, pollutant concentration and stirring time/rate). All the pollutants selected were efficiently removed at room temperature and a fractional SUPRAS phase volume of 0.01. Applicability of the SUPRAS-based treatment to the efficient removal of dyes in textile effluents and benzo(a)pyrene in tap water was proved. Overall, the low cost, easy synthesis and high removal efficiency of these engineered SUPRASs make them highly promising for application in comprehensive wastewater treatments.

Supramolecular solvent-based microextraction of emerging bisphenol A replacements (colour developers) in indoor dust from public environments.

Bisphenol A (BPA) is present in a wide variety of materials and it is a well-known endocrine disruptor that is widespread in indoor and outdoor environments. For this reason, industry has introduced a variety of replacements, such as Bisphenol S (BPS) or Bisphenol F (BPF), and other less known structural analogs, such as BPS-MAE, D-8 or TGSA. These emerging potential contaminants have been identified in thermal paper products, according to recent studies, but their potential toxic effects and their migration into the environment remain unclear. In this study, we report for the first time the presence of emerging BPA replacements in indoor dust from public environments (shops, restaurants, etc.). For this purpose, we optimized a novel supramolecular solvent (SUPRAS)-based microextraction method. SUPRAS are multi-target solvents made up of self-assembled amphiphiles. They offer multiple extraction interactions (dispersion, polar, hydrophobic, etc.) and they constitute excellent candidates to develop generic and fast sample treatment procedures at low cost. By this method, emerging BPA replacements (BPS-MAE, D-8 and TGSA) were detected in dust at median concentrations in the range 6-22 ng g-1 (around ten times lower than BPS) with detection frequencies in the range 50-90%. These results constitute a first insight into the migration of emerging BPA replacements into the environment via indoor dust, which is a common route of human exposure to contaminants.

Mass spectrometric identification of in vitro-generated metabolites of two emerging organophosphate flame retardants: V6 and BDP.

The aim of the present study was to investigate the in vitro metabolism of two emerging organophosphate flame retardants, namely tetrekis(2-chlorethyl)dichloroisopentyldiphosphate (V6) and bisphenol-A bis-diphenyl phosphate (BDP) in human liver microsomes (HLMs), HLM S9 fractions and in human serum. In particular, the role of cytochrome P450 (CYPs) enzymes and/or paraoxonases (PONs) in the formation of V6 and BDP phase I metabolites was studied. Mono-, di-hydroxylated and hydrolytic phase I metabolites of V6 were mainly formed by CYPs in HLMs, while hydrolytic and O-dealkylated phase I metabolites of BDP were generated by PONs mainly in serum experiments. Limited number of glucuronidated and sulfated phase II metabolites were also identified for the two chemicals. The activity of seven recombinant CYPs (rCYPs) including rCYP1A2, rCYP2B6, rCYP2C9, rCYP2C19, rCYP2D6, rCYP2E1 and rCYP3A4 in the in vitro phase I metabolism of V6 and BDP was investigated. The formation of V6 metabolites was catalyzed by several enzymes, especially rCYP1A2 that was responsible for the exclusive formation of two metabolites, one primary (M1) and its secondary metabolite (M9). For BDP, only one phase I metabolite (MM1) was catalyzed by the seven rCYPs. Collectively, these results indicate that CYPs have a predominant role in the metabolism of V6, while PONs have a predominant role in BDP in vitro metabolism. These results are a starting point for future studies involving the study of the toxicity, bioaccumulation and in vivo biomonitoring of V6 and BDP.

Presence of diphenyl phosphate and aryl-phosphate flame retardants in indoor dust from different microenvironments in Spain and the Netherlands and estimation of human exposure.

Phosphate flame retardants (PFRs) are ubiquitous chemicals in the indoor environment. Diphenyl phosphate (DPHP) is a major metabolite and a common biomarker of aryl-PFRs. Since it is used as a chemical additive and it is a common impurity of aryl-PFRs as well as a degradation product, its presence in indoor dust as an additional source of exposure should not be easily ruled out. In this study, DPHP (and TPHP) are measured in indoor dust in samples collected in Spain and in the Netherlands (n=80). Additionally, the presence of other emerging aryl-PFRs was monitored by target screening. TPHP and DPHP were present in all samples in the ranges 169-142,459ng/g and 106-79,661ng/g, respectively. DPHP concentrations were strongly correlated to the TPHP levels (r=0.90, p<0.01), suggesting that DPHP could be present as degradation product of TPHP or other aryl-PFRs. Estimated exposures for adults and toddlers in Spain to TPHP and DPHP via dust ingestion (country for which the number of samples was higher) were much lower than the estimated reference dose (US EPA) for TPHP. However, other routes of exposure may contribute to the overall internal exposure (diet, dermal contact with dust/consumer products and inhalation of indoor air). The estimated urinary DPHP levels for adults and toddlers in Spain (0.002-0.032ng/mL) as a result of dust ingestion were low in comparison with the reported levels, indicating a low contribution of this source of contamination to the overall DPHP exposure. Other aryl-PFRs, namely cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), 2-ethylhexyl diphenyl phosphate (EDPHP), isodecyl diphenyl phosphate (IDP) and bisphenol A bis(diphenyl phosphate) (BDP), were all detected in indoor dust, however, with lower frequency.

Bisphenol A and replacements in thermal paper: A review.

Thermal paper contains potentially toxic compounds such as bisphenol A (BPA), which is used as a color developer. BPA has been reported in thermal paper in concentrations up to 42,600 µg g-1. The exposure to BPA via dermal transfer has been recently discussed as a significant contribution to the overall human exposure and the estimated daily intake (EDI) has been reported up to 218 µg d-1. BPA has been also detected in recycled paper with concentrations up to 46 µg g-1. Due to the fact that BPA is a known endocrine disruptor and migrates from materials, regulatory restrictions have been established to prevent risks for the human health. As a consequence, structural analogues, such as bisphenol S (BPS) have been introduced into the market. Little is known about the presence and toxicity of these emerging replacements, and concern has risen about them. The present review gives an overview of the occurrence and levels of BPA and replacements in thermal paper. BPA is still the most common color developer found in thermal paper, followed by BPS. The analytical methods used for quantification of BPA and BPA replacements in paper products are also reviewed. BPA is transferred from thermal paper products to the finger pads upon handling it. Paper-skin transfer followed by penetration of BPA depends on conditions (e.g. greasiness of fingers and use of hand cream). It is, however, still debated whether thermal paper as a source for human exposure contributes significantly to the overall internal BPA exposure.

Bisphenol A alternatives in thermal paper from the Netherlands, Spain, Sweden and Norway. Screening and potential toxicity.

Thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer. Because of its known endocrine disrupting effects, structural analogues to BPA, such as bisphenol S (BPS), D-8 and Pergafast 201, have been used as alternatives, but little is known about the presence and toxicological effects of alternatives other than BPS. In this study, thermal paper is screened by direct probe ambient mass spectrometry (rapid pre-screening method not requiring sample preparation) and by liquid chromatography (LC) with high resolution time-of flight (TOF-MS) mass spectrometry. Cash receipts and other thermal paper products (cinema tickets, boarding passes and luggage tags) were analyzed. Besides BPA and BPS, other developers only recently reported (Pergafast 201, D-8) or to the best of our knowledge not reported before (D-90, TGSA, BPS-MAE) were frequently found as well as some related unreported impurities (2,4-BPS that is a BPS related impurity and a TGSA related impurity). To gain some insight into the potential estrogenicity of the detected developers, a selection of extracts was further analyzed using a LC-nanofractionation platform in combination with cell-based bioassay testing. These preliminary results seems to indicate very low or absence of estrogenic activity for Pergafast 201, D-8, D-90, TGSA and BPS-MAE in comparison to BPA and BPS, although further dose-response tests with authentic standards are required to confirm these results. Compounds for which standards were available were also tested for developmental toxicity and neurotoxicity using zebrafish (Danio rerio) embryos. TGSA and D-8 induced similar teratogenic effects as BPA in zebrafish embryos. BPS and 2,4-BPS did not induce any developmental effects but 2,4-BPS did alter the locomotor activity at the tested concentration. Our findings suggest that the alternatives used as alternatives to BPA (except BPS) might not be estrogenic. However, TGSA and D-8 showed abnormal developmental effects similar to BPA.