ABSTRACT
Photodegradation of plastic consumer products is known to accelerate weathering and facilitate the release of chemicals and plastic particles into the aquatic environment. However, these processes are complex. In our presented pilot study, eight plastic consumer products were leached in distilled water under strong ultraviolet (UV) light simulating eight months of Central European climate and compared to their respective dark controls (DCs). The leachates and formed plastic particles were exploratorily characterized using a range of chemical analytical tools to describe degradation and leaching processes. These techniques covered (a) microplastic analysis, showing substantial liberation of plastic particles further increased under UV exposure, (b) non-targeted mass spectrometric characterization of the leachates, revealing several hundreds of chemical features with typically only minor agreement between the UV exposure and the corresponding DCs, (c) target analysis of 71 organic analytes, of which 15 could be detected in at least one sample, and (d) metal(loid) analysis, which revealed substantial release of toxic metal(loid)s further enhanced under UV exposure. A data comparison with the US-EPA's ToxVal and ToxCast databases showed that the detected metals and organic additives might pose substantial health and environmental concerns, requiring further study and comprehensive impact assessments.
ABSTRACT
Sulfamethoxazole (SMX) passes through conventional wastewater treatment plants (WWTPs) mainly unaltered. Under anoxic conditions sulfate-reducing bacteria can transform SMX but the fate of the transformation products (TPs) and their prevalence in WWTPs remain unknown. Here, we report the anaerobic formation and aerobic degradation of SMX TPs. SMX biotransformation was observed in nitrate- and sulfate-reducing enrichment cultures. We identified 10 SMX TPs predominantly showing alterations in the heterocyclic and N4-arylamine moieties. Abiotic oxic incubation of sulfate-reducing culture filtrates led to further degradation of the major anaerobic SMX TPs. Upon reinoculation under oxic conditions, all anaerobically formed TPs, including the secondary TPs, were degraded. In samples collected at different stages of a full-scale municipal WWTP, anaerobically formed SMX TPs were detected at high concentrations in the primary clarifier and digested sludge units, where anoxic conditions were prevalent. Contrarily, their concentrations were lower in oxic zones like the biological treatment and final effluent. Our results suggest that anaerobically formed TPs were eliminated in the aerobic treatment stages, consistent with our observations in batch biotransformation experiments. More generally, our findings highlight the significance of varying redox states determining the fate of SMX and its TPs in engineered environments.
Subject(s)
Sulfamethoxazole , Wastewater , Sulfamethoxazole/metabolism , Wastewater/chemistry , Anaerobiosis , Waste Disposal, Fluid , Water Pollutants, Chemical/metabolism , AerobiosisABSTRACT
The presence of contaminants of emerging concern in aquatic ecosystems represents an ever-increasing environmental problem. Aquatic biota is exposed to these contaminants, which can be absorbed and distributed to their organs. This study focused on the assessment, distribution, and ecological risk of 32 CECs in a Spanish river impacted by effluents from a wastewater treatment plant, analyzing the organs and plasma of common carp. Environmental concentrations in water and sediment were examined at sites upstream and downstream of the wastewater treatment plant. The two downstream sites showed 15 times higher total concentrations (12.4 µg L-1 and 30.1 µg L-1) than the two upstream sites (2.08 µg L-1 and 1.66 µg L-1). Half of the CECs were detected in fish organs, with amantadine having the highest concentrations in the kidney (158 ng g-1 w.w.) and liver (93 ng g-1 w.w.), followed by terbutryn, diazepam, and bisphenol F in the brain (50.2, 3.82 and 1.18 ng g-1 w.w.). The experimental bioaccumulation factors per organ were compared with the bioconcentration factors predicted by a physiologically based pharmacokinetic model, obtaining differences of one to two logarithmic units for most compounds. Risk quotients indicated a low risk for 38 % of the contaminants. However, caffeine and terbutryn showed an elevated risk for fish. The mixed risk quotient revealed a medium risk for most of the samples in the three environmental compartments: surface water, sediment, and fish.
Subject(s)
Environmental Monitoring , Geologic Sediments , Wastewater , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Wastewater/chemistry , Animals , Geologic Sediments/chemistry , Risk Assessment , Carps , Rivers/chemistry , Spain , FishesABSTRACT
In this work, we developed a reactivity-based strategy to identify functional groups of unknown analytes, which can be applied as classifier in non-target analysis with gas chromatography. The aim of this strategy is to reduce the number of potential candidate structures generated for a molecular formula determined by high resolution mass spectrometry. We selected an example of 18 isomers with the molecular formula C12H10O2 to test the performance of different derivatization reagents, whereas our aim was to select mild and fast reaction conditions. Based on the results for the isomers, we developed a four-step workflow for the identification of functional groups containing oxygen.
ABSTRACT
The variety of polymers utilized in medical devices demands for testing of extractables and leachables according to ISO 10993-18:2020 in combination with ISO 10993-1:2018. The extraction of the materials involves the use of organic solvents as well as aqueous buffers to cover a wide range of polarity and pH-values, respectively. To estimate patient exposure to chemicals leaching from a polymer in direct body contact, simulating solvents are applied to best mimic the solubilization and partitioning behavior of the related tissue or body fluid. Here we apply linear solvation energy relationship (LSER) models to predict blood/water and adipose tissue/water partition coefficients. We suggest this predictive approach to project levels of potential leachables, design extraction experiments, and to identify the optimal composition of simulating extraction solvents. We compare our predictions to LSER predictions for commonly applied surrogates like ethanol/water mixtures, butanol, and octanol as well as olive oil, butanone, 1,4-dioxane for blood and adipose tissue, respectively. We therefore selected a set of 26 experimentally determined blood/water partition coefficients and 33 adipose tissue/water partition coefficients, where we demonstrate that based on the root mean squared error rmse the LSER approach performs better than surrogates like octanol or butanol and equally well as 60:40 ethanol/water for blood. For adipose tissue/water partitioning, the experimentally determined octanol/water partition coefficient performs best but the rmse is at the same range as our LSER approach based on experimentally determined descriptors. Further, we applied our approach for 248 extractables where we calculated blood/low density polyethylene (LDPE) and adipose tissue/LDPE partition coefficients. By this approach, we successfully identified chemicals of potential interest to a toxicological evaluation based on the total risk score.
Subject(s)
Polyethylene , Water , Humans , Solvents/chemistry , Water/chemistry , Octanols/chemistry , Ethanol , Adipose Tissue , ButanolsABSTRACT
The acidity constant in the form of pKa is one of the most important physicochemical quantities. There are prediction tools available for calculating the pKa , but they only deliver precise calculated values for a relatively small set of chemicals. For complex structures with multiple functional groups in particular, the error in the predicted pKa is high due to the application domain of the corresponding models. Thus, we aim to enlarge the dataset of experimentally determined pKa values using capillary electrophoresis. We, therefore, selected various pyridines, imidazoles, and oximes to determine the pKa values using the internal standard approach and the classical method. Especially oximes were not investigated in the past, and predictions for them include larger errors. Thus, our experimentally determined values could contribute to an improved understanding of various functional groups impacting the pKa values and serve as additional datasets to develop improved pKa prediction tools.
Subject(s)
Imidazoles , Oximes , Hydrogen-Ion Concentration , Electrophoresis, Capillary/methodsABSTRACT
Aromatic aldehydes are ubiquitous in humans' everyday life. As aldehydes, they can form imines (Schiff bases) with amino groups of skin proteins, leading to immune response-triggered allergic contact dermatitis. Many known aromatic aldehydes are considered as weak or nonsensitizers, but others like atranol and chloratranol, two components of the fragrance oak moss absolute, show strong sensitization potency. This large discrepancy in potency and, in particular, the underlying reaction mechanisms are only little understood so far. To reduce this knowledge gap, our chemoassay employing glycine-para-nitroanilide (Gly-pNA) as an amino model nucleophile was applied to 23 aromatic aldehydes. The determined Gly-pNA second-order rate constants for imine formation (k1 ≤ 2.85 L·mol-1·min-1) and the imine stability constant (K ≤ 333 L·mol-1) are on the lower end of the known amino reactivity scale for aldehydes, confirming many aromatic aldehydes as less potent sensitizers in line with animal and human data. The substantially higher sensitization potency of atranol and chloratranol, in turn, is reflected by their unique reaction chemistry profiles, inter alia, identifying them as cross-linkers able to form thermodynamically more stable epitopes with skin proteins (despite low formation kinetics, k1). The discussion further includes a comparison of experimentally determined k1 values with computed reactivity data (Taft σ*), the impact of the substitution pattern of the aryl ring on the reactivity with Gly-pNA, and analytically determined adduct patterns. Overall, this work provides new insights into the reaction of aromatic aldehydes with amino groups under aqueous conditions and fosters a better understanding of the chemistry underlying skin sensitization.
Subject(s)
Aldehydes , Dermatitis, Allergic Contact , Animals , Humans , Aldehydes/metabolism , Skin/metabolism , Dermatitis, Allergic Contact/metabolism , Schiff Bases , Glycine/metabolismABSTRACT
To reduce the need for animal tests, in vitro assays are often used as alternative methods. To derive toxic doses for higher tier organisms from in vitro assay results, quantitative in vitro-in vivo extrapolation (qIVIVE) based on physiological-based toxicokinetic (PBTK) models is typically the preferred approach. Such PBTK models require many input parameters to address the route from dose to target site concentration. However, respective data is very often not available. Hence, our aim is to call attention to an alternative way to build a link between animal (in vivo) and cell-derived (in vitro) toxicity data. To this end, we selected the carcinogenic chemical benzo[a]pyrene (BaP) for our study. Our approach relates both in vitro assay and in vivo data to a main intermediate marker structure for carcinogenicity on the subcellular level - the BaP-DNA adduct BaP-7,8-dihydrodiol-9,10-epoxide-deoxyguanosine. Thus, BaP dose is directly linked to a measure of the toxicity-initiating event. We used Syrian hamster embryo (SHE) and Balb/c 3T3 cell transformation assay as in vitro data and compared these data to outcomes of in vivo carcinogenicity tests in rodents. In vitro and in vivo DNA adduct levels range within three orders of magnitude. Especially metabolic saturation at higher doses and interspecies variabilities are identified and critically discussed as possible sources of errors in our simplified approach. Finally, our study points out possible routes to overcome limitations of the envisaged approach in order to allow for a reliable qIVIVE in the future.
ABSTRACT
Passive equilibrium sampling of chemical mixtures from different human post-mortem tissues (liver, brain (cerebrum and cerebellum), adipose tissue) and blood was combined with instrumental analysis using direct sample introduction (DSI) GC-MS/MS and bioanalytical profiling using in vitro bioassays targeting the activation of the aryl hydrocarbon receptor (AhR-CALUX), the adaptive stress response (AREc32) and cytotoxicity. The tissues stemmed from pathology samples collected in two German cities and covered males and females aged 21 to 100 with a mean age of 67 years. Neutral organic chemicals were extracted using polydimethylsiloxane (PDMS) at mass ratios of tissue to PDMS of approximately 6 for blood, 3 for adipose tissue and 10 for liver and brain. Amounts of chemicals in PDMS were converted to lipid-associated concentrations using previously measured partition constants that were chemical-independent despite covering eight orders of magnitude in hydrophobicity. Up to 35 of 99 targeted chemicals were detected in 6 tissues of 16 individuals (88 samples in total), among them legacy persistent organic pollutants (POP) such as DDT and derivatives and polychlorinated biphenyls (PCB) but also modern pesticides and chemicals present in consumer products. POPs were highest in adipose tissue and lipid-associated concentrations increased with age, while concentrations of fragrance materials such as galaxolide were independent of age. In tissues from the same individual, chemical concentrations mostly increased from similar levels in brain and blood to higher levels in liver and highest in adipose tissue. However, easily degradable chemicals such as phenanthrene were mainly detected in blood and brain, and very hydrophilic chemicals were least abundant in adipose tissue. The passive sampling method allows a direct comparison of chemical burden between different tissues and may have forensic applications, for example to study internal distributions or to use one tissue type as a proxy for others. The sum of concentrations of the detected chemicals was positively correlated with the bioassay responses but mixture modeling showed that the detected chemicals explained less than 2% of the activation of the AhR and less than 0.5% of cytotoxicity. This means that more than 10,000 chemicals would need to be included in an analytical method to capture all the effects with many chemicals potentially being below detection limits but still contributing to mixture effects. Therefore, we propose a smart combination of chemical analysis and bioassays to quantify priority chemicals but use bioassay responses as effect-scaled concentrations to capture the entire exposome in future epidemiological studies.
Subject(s)
Polychlorinated Biphenyls , Water Pollutants, Chemical , Aged , Biological Assay , Female , Humans , Male , Organic Chemicals , Silicones , Tandem Mass Spectrometry , Water Pollutants, Chemical/analysisABSTRACT
Equilibrium passive sampling employing polydimethylsiloxane (PDMS) as a sampling phase can be used for the extraction of complex mixtures of organic chemicals from lipid-rich biota. We extended the method to lean tissues and more hydrophilic chemicals by implementing a mass-balance model for partitioning between lipids, proteins, and water in tissues and by accelerating uptake kinetics with a custom-built stirrer that effectively decreased time to equilibrium to less than 8 days even for a homogenized liver tissue with an only 4% lipid content. The partition constants log Klipid/PDMS between tissues and PDMS were derived from measured concentration in PDMS and the mass-balance model and were very similar for 40 neutral chemicals with octanol-water partition constants 1.4 < log Kow < 8.7, that is, log Klipid/PDMS of 1.26 (95% CI, 1.13-1.39) for the adipose tissue, 1.16 (1.00-1.33) for the liver, and 0.58 (0.42-0.73) for the brain. This conversion factor can be applied to interpret chemical analysis and in vitro bioassays after additionally accounting for a small fraction of coextracted lipids of <0.7% of the PDMS weight. PDMS is more widely applicable for passive sampling of mammalian tissues than previously thought, both, in terms of diversity of chemicals and the range of lipid contents of tissues and, therefore, an ideal method for human biomonitoring to be combined with in vitro bioassays.
Subject(s)
Water Pollutants, Chemical , Animals , Humans , Kinetics , Lipids , Organic Chemicals , Polymers , Water Pollutants, Chemical/analysisABSTRACT
Today more and more data are freely available. Based on these big datasets deep neural networks (DNNs) rapidly gain relevance in computational chemistry. Here, we explore the potential of DNNs to predict chemical properties from chemical structures. We have selected the octanol-water partition coefficient (log P) as an example, which plays an essential role in environmental chemistry and toxicology but also in chemical analysis. The predictive performance of the developed DNN is good with an rmse of 0.47 log units in the test dataset and an rmse of 0.33 for an external dataset from the SAMPL6 challenge. To this end, we trained the DNN using data augmentation considering all potential tautomeric forms of the chemicals. We further demonstrate how DNN models can help in the curation of the log P dataset by identifying potential errors, and address limitations of the dataset itself.
ABSTRACT
Perfluoroalkyl acids (PFAAs) mostly exist as ionic compounds that are of major concern because of their accumulative behavior. The discussion about their risk is ongoing considering the increasing production of structurally similar alternatives. We conducted model calculations based on equilibrium distribution coefficients that allow studying the distribution of PFAAs and their alternatives in various mammalian organs through comparison to empirical measurements in humans and rats. The calculations rely on experimentally determined distribution coefficients of a series of PFAAs and 4 of their alternatives to physiological matrices such as structural proteins, storage lipids, membrane lipids, albumin, and fatty acid binding protein (FABP). The relative sorption capacities in each organ were calculated from the combination of distribution coefficients and physiological data. The calculated distribution of PFAAs and alternatives within the organs showed that albumin and membrane lipids and, to a lesser extent, structural proteins have the highest relative sorption capacities for the compounds. Sorption to FABP is only relevant in the distribution of short-chain PFAAs. Storage lipids play a minor role in the distribution of all studied compounds. Our calculated distribution of PFAAs was evaluated by comparison to reported PFAA concentrations in various organs. Environ Toxicol Chem 2021;40:910-920. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Water Pollutants, Chemical , Animals , Fluorocarbons/analysis , Mammals , Rats , Water Pollutants, Chemical/analysisABSTRACT
Solvent extracts of mammalian tissues and blood contain a large amount of co-extracted matrix components, in particular lipids, which can adversely affect instrumental analysis. Clean-up typically degrades non-persistent chemicals. Alternatively, passive sampling with the polymer polydimethylsiloxane (PDMS) has been used for a comprehensive extraction from tissue without altering the mixture composition. Despite a smaller fraction of matrix being co-extracted by PDMS than by solvent extraction, direct analysis of PDMS extracts was only possible with direct sample introduction (DSI) GC-MS/MS, which prevented co-extracted matrix components entering the system. Limits of quantitation (LOQ) ranged from 4 to 20 pg µL-1 ethyl acetate (PDMS extract) for pesticides and persistent organic pollutants (POPs). The group of organophosphorus flame retardants showed higher LOQs up to 107 pg µL-1 due to sorption to active sites at the injection system. Intraday precision ranged between 1 and 10%, while the range of interday precision was between 1 and 18% depending on the analyte. The method was developed using pork liver, brain, and fat as well as blood and was then applied to analyze human post-mortem tissues where polychlorinated biphenyls (PCBs) as well as dichlorodiphenyltrichloroethane (DDT) and DDT metabolites were detected. Graphical abstract.
Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Organic Chemicals/analysis , Polymers/chemistry , Animals , Limit of Detection , Organic Chemicals/blood , Reference Standards , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
The zebrafish embryo (Danio rerio) has developed into one of the most important nonsentient animal models for the hazard assessments of chemicals, but the processes governing its toxicokinetics (TK) are poorly understood. This study compares the uptake of seven test compounds into the embryonic body and the yolk sac of the zebrafish embryo using TK experiments, a dialysis approach, thermodynamic calculations, and kinetic modeling. Experimental data show that between 95% (4-iodophenol) and 67% (carbamazepine) of the total internal amount in 26 h post fertilization (hpf) embryos and between 80 and 49% in 74 hpf embryos were found in the yolk. Thus, internal concentrations determined for the whole embryo overestimate the internal concentration in the embryonic body: for the compounds of this study, up to a factor of 5. Partition coefficients for the embryonic body and a one-compartment model with diffusive exchange were calculated for the neutral test compounds and agreed reasonably with the experimental data. For prevalently ionic test compounds at exposure pH (bromoxynil, paroxetine), however, the extent and the speed of uptake were low and could not be modeled adequately. A better understanding of the TK of ionizable test compounds is essential to allow assessment of the validity of this organismic test system for ionic test compounds.
Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Embryo, Nonmammalian/metabolism , Renal Dialysis , Toxicokinetics , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/toxicity , Yolk SacABSTRACT
Yolk is the most important temporary biological compartment of the early life stages of fish embryos. The sorption strength of a chemical to yolk components may significantly influence the distribution of that chemical in the fish embryo. We determined yolk-water partition coefficients (Kyolk/water , in liters of water per kilogram of yolk, normalized to dry wt) for 70 neutral organic chemicals. The log Kyolk/water values range from 0.76 to 6.56. On the basis of these values, we developed polyparameter linear free energy relationship models to predict yolk-water partitioning for a broad range of neutral organic chemicals with a root mean squared error of 0.37 and r2 of 0.919. These models can be applied for the prediction of internal concentrations at equilibrium (neglecting biotransformation and active transport) in the zebrafish embryo test system. Environ Toxicol Chem 2020;39:1506-1516. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Subject(s)
Egg Yolk/chemistry , Models, Biological , Organic Chemicals/chemistry , Water/chemistry , Zebrafish/metabolism , Animals , Biomass , Dialysis , Egg Proteins/analysis , Reproducibility of Results , Temperature , Volatile Organic Compounds/analysis , Water Pollutants, Chemical/chemistryABSTRACT
The search for alternatives to bioaccumulative perfluoroalkyl acids (PFAAs) is ongoing. New, still highly fluorinated alternatives are produced in hopes of reducing bioaccumulation. To better estimate this bioaccumulative behavior, we performed dialysis experiments and determined membrane/water partition coefficients, Kmem/w, of six perfluoroalkyl carboxylic acids (PFCAs), three perfluoroalkanesulfonic acids, and four alternatives. We also investigated how passive permeation might influence the uptake kinetics into cells, measuring the passive anionic membrane permeability Pion through planar lipid bilayers for six PFAAs and three alternatives. Experimental Kmem/w and Pion were both predicted well by the COSMO-RS theory (log RMSE 0.61 and 0.46, respectively). Kmem/w values were consistent with the literature data, and alternatives showed similar sorption behavior as PFAAs. Experimental Pion values were high enough to explain observed cellular uptake by passive diffusion with no need to postulate the existence of active uptake processes. However, predicted pKa and neutral permeabilities suggest that also the permeation of the neutral species should be significant in case of PFCAs. This can have direct consequences on the steady-state distribution of PFAAs across cell membranes and thus toxicity. Consequently, we propose a model to predict pH-dependent baseline toxicity based on Kmem/w, which considers the permeation of both neutral and anionic species.
Subject(s)
Fluorocarbons , Water , Permeability , Renal Dialysis , ToxicokineticsABSTRACT
The article Metabolites of the alkyl pyrrolidone solvents NMP and NEP in 24-h urine samples of the German Environmental Specimen Bank from 1991 to 2014.
ABSTRACT
A correct description of the concentration and distribution of particle bound polycyclic aromatic hydrocarbons is important for risk assessment of atmospheric particulate matter. A new targeted GC-MS/MS method was developed for analyzing 64â¯PAHs including compounds with a molecular weight >300, as well as nitro-, methyl-, oxy- and hydroxyl derivatives in a single analysis. The instrumental LOD ranged between 0.03 and 0.7â¯pg/µL for PAHs, 0.2-7.9â¯pg/µL for hydroxyl and oxy PAHs, 0.1-7.4â¯pg/µL for nitro PAHs and 0.06-0.3â¯pg/µL for methyl-PAHs. As an example for the relevance of this method samples of PM10 were collected at six sampling sites in Medellin, Colombia, extracted and the concentration of 64 compounds was determined. The 16â¯PAHs from the EPA priority list contributed only from 54% to 69% to the sum of all analyzed compounds, PAH with high molecular weight accounted for 8.8%-18.9%. Benzo(a)pyrene equivalents (BaPeq) were calculated for the estimation of the life time cancer (LCR). The LCR according to the samples ranged from 2.75â¯×â¯10-5 to 1.4â¯×â¯10-4 by a calculation with toxic equivalent factors (TEF) and 5.7â¯×â¯10-5 to 3.8â¯×â¯10-4 with potency equivalent factor (PEF). By using the new relative potency factors (RPF) recommended by US Environmental Protection Agency (U.S.EPA) the LCR ranged from 1.3â¯×â¯10-4 to 7.2â¯×â¯10-4. Hence, it was around six times higher than the well-known TEF. The novel method enables the reliable quantification of a more comprehensive set of PAHs bound on PM and thus will facilitate and improve the risk assessment of them.
Subject(s)
Air Pollutants/analysis , Environmental Monitoring/methods , Polycyclic Aromatic Hydrocarbons/analysis , Benzo(a)pyrene/analysis , Chromatography, Gas , Colombia , Gas Chromatography-Mass Spectrometry , Particulate Matter/analysis , Risk Assessment , Tandem Mass SpectrometryABSTRACT
Perfluoroalkyl acids (PFAAs) are persistent, ubiquitous environmental contaminants and their long-chain representatives are bioaccumulative. The phase-out of these compounds (e.g. PFOA and PFOS) shifted the production to alternatives. However, little is known about the bioaccumulative behaviour of the alternatives, which are still highly fluorinated. PFAAs are predominantly detected in blood, where they bind to the transport protein serum albumin. This sorption can be described by the albumin/water partition coefficient. It is unclear whether the partition coefficients of the alternatives are lower than or in the same range as those of classical PFAAs. We determined albumin/water partition coefficients for seven perfluoroalkyl carboxylates, three perfluoroalkane sulfonates and four alternatives by dialysis experiments in a physiologically representative system. Quantification was done by LC-MS/MS and a mass balance approach. Logarithmic albumin/water partition coefficients for PFAAs range from 2.8 to 4.8 [Lwater kgalbumin-1] and increase with increasing chain length. Perfluorinated sulfonates sorb more strongly than their carboxylate counterparts. The albumin/water partition coefficients for the alternatives (HFPO-DA, DONA, 9Cl-PF3ONS and PFECHS) are in the same range as for classical PFAAs. Structural modifications such as the introduction of ether groups into the chain do not reduce sorption to albumin, whereas the chlorine atom in 9Cl-PF3ONS seems to even increase the sorption to albumin. We further investigated whether the sorption strength could be affected in the presence of medium- or long-chain fatty acids. Binding competition between medium-chain fatty acids and PFAAs appeared to be possible. However, the presence of physiologically more relevant long-chain fatty acids should not alter the albumin/water partition coefficients of PFAAs.
Subject(s)
Alkanesulfonic Acids/chemistry , Carboxylic Acids/chemistry , Fluorocarbons/chemistry , Serum Albumin, Bovine/chemistry , Water/chemistry , Binding, Competitive , Chromatography, Liquid , Models, Chemical , Protein Binding , Structure-Activity Relationship , Tandem Mass SpectrometryABSTRACT
PURPOSE: The aim of this study was to get a first overview of the exposure to the solvents and reproductive toxicants N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) in Germany. NMP and NEP metabolite concentrations were determined in 540 24-h urine samples of the German Environmental Specimen Bank collected from 1991 to 2014. With these data we were able to investigate NMP/NEP exposures over time and to evaluate associated risks. METHODS: NMP metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) and NEP metabolites 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) were determined by stable isotope dilution analysis using solid phase extraction followed by derivatization (silylation) and GC-EI-MS/MS. RESULTS: We were able to quantify 5-HNMP and 2-HMSI in 98.0 and 99.6% and 5-HNEP and 2-HESI in 34.8 and 75.7% of the samples. Metabolite concentrations were rather steady over the timeframe investigated, even for NEP which has been introduced as an NMP substitute only in the last decade. Calculated median daily intakes in 2014 were 2.7 µg/kg bw/day for NMP and 1.1 µg/kg bw/day for NEP. For the combined risk assessment of NMP and NEP exposure, the hazard index based on the human biomonitoring assessment I values (HBM I values) was less than 0.1. CONCLUSIONS: Based on the investigated subpopulation of the German population, individual and combined NMP and NEP exposures were within acceptable ranges in the investigated timeframe. Sources of NEP exposure in the 90s and 00s remain elusive.