SWATH-F: A Novel Nontarget Strategy Based on the SWATH-MS Deconvolution Method Assisting in Annotating PFAS Homologues in Multisample Studies.

In order to identify emerging per- and polyfluoroalkyl substances (PFASs) and their alternatives in the environment or population, we need to perform extensive profiling of PFASs to determine their distribution in samples. The sequential window acquisition of all theoretical fragment-ion spectra (SWATH mode) is capable of obtaining a wide range of MS2 spectra but is difficult for direct identification of PFASs due to its complex MS2 spectra, and the nontarget screening method is difficult to identify due to its lack of a priori information. In this study, we demonstrated the great potential of SWATH-F, a nontarget fragment-based homologue screening method in combination with the SWATH-MS deconvolution, for detecting PFASs. We evaluated the application of SWATH-F to gradient spiked samples and real population serum samples, compared it with nontarget homologue screening in the information-dependent acquisition mode (IDA mode), and obtained better results for SWATH-F with 276% improvement (IDA:17 PFASs, SWATH-F: 64 PFASs) in identification. In addition, we automated the screening and identification process of SWATH-F to facilitate its use by researchers. SWATH-F is freely available on GitHub (https://github.com/njuIrene/SWATH-F) under an MIT license.

Nontarget Discovery of Antimicrobial Transformation Products in Wastewater Based on Molecular Networks.

Antimicrobial transformation products (ATPs) in the environment have raised extensive concerns in recent years due to their potential health risks. However, only a few ATPs have been investigated, and most of the transformation pathways of antimicrobials have not been completely elucidated. In this study, we developed a nontarget screening strategy based on molecular networks to detect and identify ATPs in pharmaceutical wastewater. We identified 52 antimicrobials and 49 transformation products (TPs) with a confidence level of three or above. Thirty of the TPs had not been previously reported in the environment. We assessed whether TPs could be classified as persistent, mobile, and toxic (PMT) substances based on recent European criteria for industrial substances. Owing to poor experimental data, definitive PMT classifications could not be established for novel ATPs. PMT assessment based on structurally predictive physicochemical properties revealed that 47 TPs were potential PMT substances. These results provide evidence that novel ATPs should be the focus of future research.

Comprehensive Exposure Studies of Per- and Polyfluoroalkyl Substances in the General Population: Target, Nontarget Screening, and Toxicity Prediction.

Novel per- and polyfluoroalkyl substances (PFASs) in the environment and populations have received extensive attention; however, their distribution and potential toxic effects in the general population remain unclear. Here, a comprehensive study on PFAS screening was carried out in serum samples of 202 individuals from the general population in four cities in China. A total of 165 suspected PFASs were identified using target and nontarget analysis, including seven identified PFAS homolog series, of which 16 PFASs were validated against standards, and seven PFASs [4:2 chlorinated polyfluorinated ether sulfonate (4:2 Cl-PFESA), 7:2 chlorinated polyfluorinated ether sulfonate (7:2 Cl-PFESA), hydrosubstituted perfluoroheptanoate (H-PFHpA), chlorine-substituted perfluorooctanoate (Cl-PFOA), chlorine-substituted perfluorononanate (Cl-PFNA), chlorine-substituted perfluorodecanoate (Cl-PFDA), and perfluorodecanedioic acid (PFLDCA n = 8)] were reported for the first time in human serum. The Tox21-GCN model (a graph convolutional neural network model based on the Tox21 database) was established to predict the toxicity of the discovered PFASs, revealing that PFASs containing sulfonic acid groups exhibited multiple potential toxic effects, such as estrogenic effects and stress responses. Our study indicated that the general population was exposed to various PFASs, and the toxicity prediction results of individual PFASs suggested potential health risks that could not be ignored.

Nontarget Discovery of Per- and Polyfluoroalkyl Substances in Atmospheric Particulate Matter and Gaseous Phase Using Cryogenic Air Sampler.

Novel per- and polyfluoroalkyl substances (PFASs) have become a key issue in global environmental studies. Although several novel PFASs have been discovered in atmospheric particulate matter through nontarget analysis, information on the environmental occurrence of novel PFASs in atmospheric gaseous phases and conventional sampling techniques is somewhat deficient. Therefore, this Article describes a new type of air sampler, the cryogenic air sampler (CAS), which was used to collect all atmospheric components simultaneously. Nontarget analysis then was performed through PFASs homologue analysis. A total of 117 PFAS homologues (38 classes) were discovered, 48 of which (13 classes) were identified with confidence Level 4 or above. Eleven chlorinated perfluoropolyether alcohols (3 classes) and four chlorinated perfluoropolyether carboxylic acids (2 classes) have been reported for the first time in this Article. This Article is also the first report of 12 hydrosubstituted perfluoroalkyl carboxylates (H-PFCAs) in the atmosphere. H-PFCAs and chlorinated perfluoropolyether carboxylic acids were mainly distributed in the particular phase. These results are evidence that novel chlorinated polyether PFASs should be the focus of future study.

Transplacental Transfer of Per- and Polyfluoroalkyl Substances Identified in Paired Maternal and Cord Sera Using Suspect and Nontarget Screening.

Novel per- and polyfluoroalkyl substances (PFASs) in various environmental media have attracted increasing attention; however, the information regarding PFASs exposure in pregnant women and fetuses is insufficient. In this study, we built and applied suspect and nontarget screening strategies based on the mass difference of the CF2, CF2O, and CH2CF2 units to select potential novel PFASs from 117 paired maternal and cord sera. In total, 10 legacy PFASs and 19 novel PFASs from 10 classes were identified to be above confidence levels 3, among which 14 were not previously reported in human serum. Novel PFASs accounted for a considerable percentage of total PFASs in pregnant women and can be transferred to fetuses at non-negligible concentrations (i.e., 27.9% and 30.3% of total PFAS intensities in maternal and cord sera, respectively). The transplacental transfer efficiency (TTE) of PFASs showed a U-shape trend in the series of perfluoroalkyl carboxylic acids, perfluoroalkyl sulfonic acids, and unsaturated perfluorinated alcohols. The TTE of novel PFASs is suggested to be structure-dependent, based on a flexible docking experiment. This study provides comprehensive TTE information on legacy and novel PFASs for the first time, and additional toxicity studies are needed to evaluate the risk of novel PFASs further.

Organophosphate Ester, 2-Ethylhexyl Diphenyl Phosphate (EHDPP), Elicits Cytotoxic and Transcriptomic Effects in Chicken Embryonic Hepatocytes and Its Biotransformation Profile Compared to Humans.

The effects of 2-ethylhexyl diphenyl phosphate (EHDPP) on cytotoxicity and mRNA expression, as well as its metabolism, were investigated using a chicken embryonic hepatocyte (CEH) assay. After incubation for 36 h, the lethal concentration 50 (LC50) was 50 ± 11 µM, suggesting that EHDPP is one of a small cohort of highly toxic organophosphate esters (OPEs). By use of a ToxChip polymerase chain reaction (PCR) array, we report modulation of 6, 11, or 16/43 genes in CEH following exposure to 0.1, 1, or 10 µM EHDPP, respectively. The altered genes were from all nine biological pathways represented on the ToxChip including bile acids/cholesterol regulation, glucose metabolism, lipid homeostasis, and the thyroid hormone pathway. After incubation for 36 h, 92.5% of EHDPP was transformed, and one of its presumed metabolites, diphenyl phosphate (DPHP), only accounted for 12% of the original EHDPP concentration. Further screening by use of high-resolution mass spectrometry revealed a novel EHDPP metabolite, hydroxylated 2-ethylhexyl monophenyl phosphate (OH-EHMPP), which was also detected in a human blood pool. Additional EHDPP metabolites detected in the human blood pool included EHMPP and DPHP. Overall, this study provided novel information regarding the toxicity of EHDPP and identified a potential EHDPP metabolite, OH-EHMPP, in both avian species and humans.

Suspect and Nontarget Screening of Per- and Polyfluoroalkyl Substances in Wastewater from a Fluorochemical Manufacturing Park.

Although per- and polyfluoroalkyl substances (PFASs) have always been a key issue in the global environmental field, there are still a lot of undiscovered PFASs in the environment due to new PFAS alternatives developed by manufacturers. Wastewater treatment plants (WWTPs), as one of the sources for PFASs, are an important part of the process of releasing new PFASs into the environment. In this study, suspect screening and PFAS homologue analysis with quadrupole time-of-flight tandem mass spectrometry were used to discover PFASs in wastewater from a WWTP near Yangtze River. Fifteen classes with 90 PFASs were identified, including 12 legacy PFASs (2 classes), 41 previously reported PFASs (7 classes), and 37 new PFASs (6 classes), and 18 of these PFASs were also detected in the nearby Yangtze River. Only 1 PFAS class was removed through the treatment processes (fold change < 1/6). Conversely, 4 PFAS classes increased through the treatment processes (fold change > 6), which could be the transformation products of PFAS precursors. These results implied that most discovered PFASs were not effectively removed in the WWTP. Chlorine-substituted perfluoroalkyl carboxylates (Cl-PFCAs) as the main component of wastewater were detected only in downstream, meaning that Cl-PFCAs in downstream possibly originated from the WWTP.

Non-Target and Suspect Screening of Per- and Polyfluoroalkyl Substances in Airborne Particulate Matter in China.

Airborne particulate matter (APM) has an important role in inhalation exposure, especially in China. The environmental occurrence of conventional and unknown per- and polyfluoroalkyl substances (PFASs) in APM remains unclear. Therefore, in this study, a two-stage experiment was designed to identify potential PFASs and to investigate their distribution in APM. Indoor and outdoor APM samples were collected from five selected cities in China. Through PFAS homologue analysis and suspect screening, 50 peaks were identified with different confidence levels (levels 1-3). Among the identified PFASs, 34 emerging PFASs including p-perfluorous nonenoxybenzenesulfonate, 6:2 polyfluoroalkyl phosphate diester, n:2 fluorotelomer sulfonates, n:2 fluorinated telomer acids, n:2 chlorinated polyfluoroalkyl ether sulfonic acids, 1:n polyfluoroalkyl ether carboxylic acids (1:n PFECAs), perfluoroalkyl dioic acids (PFdiOAs), hydro-substituted perfluoroalkyl dioic acids (H-PFdiOAs), and unsaturated perfluorinated alcohols (UPFAs) were identified in APM. In particular, 1:n PFECAs, PFdiOAs, H-PFdiOAs, and UPFAs were first detected in APM. Although human exposure to perfluorooctanoic acid via inhaled APM was noted to not be a risk (hazard quotient <0.1) in this study, the expansion of the PFASs screened in APM implies that human exposure to PFASs might be much more serious and should be considered in future risk assessments in China.

Extended Virtual Screening Strategies To Link Antiandrogenic Activities and Detected Organic Contaminants in Soils.

A tiered screening strategy based on extensive virtual fractionation and elucidation was developed to simplify identification of toxicants in complex environments. In tier1-virtual fractionation, multivariate analysis (MVA) was set up as an alternative of physical fractionation. In tier2-virtual structure elucidation, in-house quantitative structure-retention relationship (QSRR) models and toxicity simulation methods were developed to simplify nontarget identification. The efficiency of the tiered virtual strategy was tentatively verified by soil samples from a chemical park contaminated by antiandrogenic substances. Eight out of 18 sites were detected as antiandrogenic, while none of them exhibited androgenic agonist potencies. Sixty-seven peaks were selected for further identification by MVA, among which over 90% were verified in androgenic fractions in traditional effect-directed analysis (EDA). With 579 tentative structures generated by in silico fragmentation, 74% were elucidated by QSRR and 65% were elucidated by in silico toxicity prediction. All prior peaks were identified at different confidence levels with over 40% of the identified peaks above confidence level 2b, which has been increased over 40% with less than half of the time spent compared to traditional EDA. Such a combination of tiered virtual screening methods provides more efficient and rapid identifications of key toxicants at contaminated sites.

In vivo bioavailability and in vitro bioaccessibility of perfluorooctanoic acid (PFOA) in food matrices: correlation analysis and method development.

Food is a major source of human exposure to perfluorooctanoic acid (PFOA), however, PFOA bioavailability in food has not been studied. An in vivo mouse model and three in vitro methods (unified BARGE method, UBM; physiologically based extraction test, PBET; and in vitro digestion method, IVD) were used to determine the relative bioavailability and bioaccessibility of PFOA in the presence of 17 foods. PFOA was mixed with foods of different nutritional compositions and fed to mice over a 7-d period. PFOA relative bioavailability was determined by comparing PFOA accumulation in the liver following PFOA exposure via food to that in water. PFOA bioavailability relative to water ranged from 4.30 ± 0.80 to 69.0 ± 11.9% and was negatively correlated with lipid content (r = 0.76). This was possibly due to competitive sorption of free fatty acids with PFOA onto transporters on intestine epithelial cells. Besides, cations in the gastrointestinal tract, such as Ca(2+) and Mg(2+), are capable of complexing PFOA and partitioning to the lipid phase. On the other hand, when assessed using in vitro assays, PFOA bioaccessibility varied with methods, being 8.7-73% (UBM), 9.8-99% (PBET), and 21-114% (IVD). PFOA bioaccessibility was negatively correlated with lipid content when assessed using UBM (r = 0.82); however, a poor correlation with food composition was observed for PBET and IVD (r = 0.01-0.50). When in vivo and in vitro data were compared, a strong correlation was observed for UBM (r = 0.79), but poor relationships were observed for PBET and IVD (r = 0.11-0.22). This was probably because the higher lipolysis ability and presence of Ca(2+) and Mg(2+) in the gastrointestinal fluid of UBM resulted in a lower potential to form stable micelles compared to PBET and IVD. These results indicated that PFOA relative bioavailability was mainly affected by lipid content in foods, and UBM has the potential to determine PFOA bioaccessibility in food samples.

Machine learning-enhanced molecular network reveals global exposure to hundreds of unknown PFAS.

Unknown forever chemicals like per- and polyfluoroalkyl substances (PFASs) are difficult to identify. Current platforms designed for metabolites and natural products cannot capture the diverse structural characteristics of PFAS. Here, we report an automatic PFAS identification platform (APP-ID) that screens for PFAS in environmental samples using an enhanced molecular network and identifies unknown PFAS structures using machine learning. Our networking algorithm, which enhances characteristic fragment matches, has lower false-positive rate (0.7%) than current algorithms (2.4 to 46%). Our support vector machine model identified unknown PFAS in test set with 58.3% accuracy, surpassing current software. Further, APP-ID detected 733 PFASs in real fluorochemical wastewater, 39 of which are previously unreported in environmental media. Retrospective screening of 126 PFASs against public data repository from 20 countries show PFAS substitutes are prevalent worldwide.

Unveiling intricate transformation pathways of emerging contaminants during wastewater treatment processes through simplified network analysis.

As the key stage for purifying wastewater, elimination of emerging contaminants (ECs) is found to be fairly low in wastewater treatment plants (WWTPs). However, less knowledge is obtained regarding the transformation pathways between various chemical structures of ECs under different treatment processes. This study unveiled the transformation pathways of ECs with different structures in 15 WWTPs distributed across China by simplified network analysis (SNA) we proposed. After treatment, the molecular weight of the whole component of wastewater decreased and the hydrophilicity increased. There are significant differences in the structure of eliminated, consistent and formed pollutants. Amino acids, peptides, and analogues (AAPAs) were detected most frequently and most removable. Benzenoids were refractory. Triazoles were often produced. The high-frequency reactions in different WWTPs were similar, (de)methylation and dehydration occurred most frequently. Different biological treatment processes performed similarly, while some advanced treatment processes differed, such as a significant increase of -13.976 (2HO reaction) paired mass distances (PMDs) in the chlorine alone process. Further, the common structural transformation was uncovered. 4 anti-hypertensive drugs, including irbesartan, valsartan, olmesartan, and losartan, were identified, along with 22 transformation products (TPs) of them. OH2 and H2O PMDs occurred most frequently and in 80.81 % of the parent-transformation product pairs, the intensity of the product was higher than parent in effluents, whose risk should be considered in future assessment activity. Together our results provide a macrography perspective on the transformation processes of ECs in WWTPs. In the future, selectively adopting wastewater treatment technology according to structures is conductive for eliminating recalcitrant ECs in WWTPs.

Occurrence of perfluoroalkyl acids including perfluorooctane sulfonate isomers in Huai River Basin and Taihu Lake in Jiangsu Province, China.

The spatial distribution of 10 perfluoroalkyl acids including linear and branched (six monotrifluoromethyl isomers) perfluorooctane sulfonate (PFOS) in surface water was investigated in Huai River Basin and Taihu Lake in Jiangsu Province, China. In the water samples from Huai River Basin, perfluorooctanoic acid (PFOA) and PFOS were the predominant compounds (mean 18 ng/L and 4.7 ng/L, respectively), while in samples from Taihu Lake, PFOA, perfluorohexanoic acid (PFHxA), and PFOS were the predominant compounds (mean 56 ng/L, 19 ng/L, and 15 ng/L, respectively). Branched PFOS (Br-PFOS) isomers accounting for 48.1% to 62.5% of total PFOS were enriched in all samples from Taihu Lake, compared to technical electrochemical fluorination (ECF) PFOS (Br-PFOS ∼30.0%), while the similar phenomena were not found in samples from Huai River Basin (Br-PFOS 29.0-35.0%). Principal component analysis (PCA) on the percentages of the individual isomer showed that the first two components accounted for 78.4% and 15.3% of the overall observed data variance. Samples from Huai River Basin were grouped together with the ECF PFOS standard suggesting the profiles were similar, while samples from Taihu Lake were grouped by themselves, suggesting that isomer profiles in these samples were different from that of Huai River Basin. The obvious difference in isomer profiles probably results from the different environmental behaviors of PFOS isomers and/or unknown sources (PFOS or PFOS precursors).

Application of particle swarm optimization algorithm in the heating system planning problem.

Based on the life cycle cost (LCC) approach, this paper presents an integral mathematical model and particle swarm optimization (PSO) algorithm for the heating system planning (HSP) problem. The proposed mathematical model minimizes the cost of heating system as the objective for a given life cycle time. For the particularity of HSP problem, the general particle swarm optimization algorithm was improved. An actual case study was calculated to check its feasibility in practical use. The results show that the improved particle swarm optimization (IPSO) algorithm can more preferably solve the HSP problem than PSO algorithm. Moreover, the results also present the potential to provide useful information when making decisions in the practical planning process. Therefore, it is believed that if this approach is applied correctly and in combination with other elements, it can become a powerful and effective optimization tool for HSP problem.

The occurrence, tissue distribution, and PBT potential of per- and polyfluoroalkyl substances in the freshwater organisms from the Yangtze river via nontarget analysis.

Numerous emerging per- and polyfluoroalkyl substances (PFASs) occur in the aquatic environment, posing a threat to aquatic ecosystems and human health. In this study, we conducted a nontarget analysis on 3 surface water samples and 92 tissue samples of 16 fish collected from the Yangtze River to investigate the patterns, tissue distribution, and environmental impacts of emerging PFASs. A total of 43 PFASs from 11 classes were identified, including 17 legacy PFASs and 26 emerging PFASs. Among the 43 PFASs, seven PFASs were reported in biota for the first time while five PFASs were reported in the environment for the first time. Chlorine substituted perfluoroalyl ether sulfonic acids were the major emerging PFASs detected in organisms. Our results showed that most emerging PFASs tended to accumulate in the liver whereas perfluorinated sulfonamides tended to accumulate in the blood, and all of the emerging PFASs accumulated less in the muscle. Methods for evaluating the persistence, bioaccumulation, and toxicity (PBT) of PFASs were developed by combining the in-silico methods and experimental methods. Long-chain PFASs were found to have extremely high PBT scores compared to short-chain PFASs. Additionally, most emerging PFASs exhibited comparable PBT characteristics with legacy PFASs, especially Cl-substituted PFASs.

Potential effects of Ag ion on the host by changing the structure of its gut microbiota.

Silver (Ag) can change the structure of the gut microbiota (GM), but how such change may affect host health is unknown. In this study, mice were exposed to silver acetate daily for 120 days. During this period, Ag accumulation in the liver was measured, its effects on GM structure were analyzed, and potential metabolic changes in liver and serum were examined. Although Ag accumulation remained unchanged in most treatments, the ratio of Firmicutes to Bacteroidetes at the phylum level increased and changes in the relative abundance of 33 genera were detected, suggesting that Ag altered the energy metabolism of mice via changes in the gut GM. In serum and liver, 34 and 72 differentially expressed metabolites were identified, respectively. The KEGG pathways thus enriched mainly included those involving the metabolism of amino acids, organic acids, lipids, and purine. Strong correlations were found between 33 % of the microorganisms with altered relative abundances and 46 % of the differentially expressed metabolites. The resulting clusters yielded two communities responsible for host inflammation and energy metabolism. Overall, these results demonstrate potential effects of Ag on the host, by changing its GM structure, and the need to consider them when evaluating the health risk of Ag.

Classification and identification of polar pollutants on microplastics from freshwater using nontarget screening strategy.

Microplastics (MPs) cause an increased threat to the freshwater environment by adsorbing pollutants on their large surface area. Considering their adsorption characteristics, non-polar pollutants with high distribution coefficients have been studied extensively. However, comprehensive research on the types of polar pollutants adsorbed by MPs is lacking. In this study, a nontarget screening strategy, including classification and identification, was performed to analyze the pollutants adsorbed by MPs in Tai Lake and the Yangtze River. Compared with the pollutants adsorbed or added to raw plastics, more types of polar pollutants were found on MPs from freshwater. The nontarget classification of 4723 features on MPs from freshwater and 680 features from raw plastics were annotated based on the mass spectrometry spectra. Further identification with multiple platforms identified hundreds of pollutants absorbed by MPs in Tai Lake and Yangtze River, including industrial intermediates, medicines, and surfactants, exceeding those adsorbed by raw plastics, showing an enrichment of the pollutants on MPs in freshwater by secondary adsorption. Our study is the first to use nontarget analysis to comprehensively demonstrate MP adsorption and release of pollutants in freshwater environment, providing a significant reference for the research of MPs and the management of the water environment.

Changes in Gut Microbiota Structure: A Potential Pathway for Silver Nanoparticles to Affect the Host Metabolism.

Silver nanoparticles (AgNPs) are one of the most widely used NPs. Their adverse effects on either the host or its gut microbiota (GM) have been examined. Nevertheless, whether the GM plays any role in AgNP toxicity to the host remains unclear. In the present study, AgNPs were administered to mice by oral gavage once a day for 120 days. A significant dose-dependent accumulation of Ag in the liver was observed, with a steady state reached within 21 days. The AgNPs changed the structure of the GM, mainly with respect to microorganisms involved in the metabolism of energy, amino acids, organic acids, and lipids, as predicted in a PICRUST analysis. Effects of the AgNPs on liver metabolism were also demonstrated, as a KEGG pathway analysis showed the enrichment of pathways responsible for the metabolism of amino acids, purines and pyrimidine, lipids, and energy. More interestingly, the changes in GM structure and liver metabolism were highly correlated, evidenced by the correlation between ∼23% of the differential microorganisms at the genus level and ∼60% of the differential metabolites. This implies that the metabolic variations in liver as affected by AgNPs were partly attributable to NP-induced changes of GM structure. Therefore, our results demonstrate the importance of considering the roles of GM in the toxicity of NPs to the host in evaluations of the health risks of NPs.

Screening priority indicator pollutants in full-scale wastewater treatment plants by non-target analysis.

Wastewater treatment plants (WWTPs) are the main sources of emerging contaminants (ECs) in aquatic environment. However, the standards for limiting emerging pollutants in effluent are extremely lacking. We investigated the occurrence and removal of emerging pollutants in 16 WWTPs in China using non-target analysis. 568 substances screened out were divided into 9 kinds including 167 pharmaceuticals, 113 natural substances, 85 pesticides, 86 endogenous substances, 64 chemical raw materials, 14 personal care products, 17 food additives, 6 hormones and 16 others. And they were divided into 5 fates. Pesticides and pharmaceutical compounds seemed to be the most notable categories, the kinds detected in each sample is the largest compared with other compounds. Besides, the average removal rate of pesticides and pharmaceuticals in all WWTPs were the lowest, at 9.54% and 23.77%, respectively. Priority pollutants were screened by considering distribution of pollutants with different fates. Pollutants with the same fate especially "consistent" in different WWTPs had attracted attention. 4 potential priority pollutants including metoprolol, carbamazepine, 10, 11-dihydro-10, 11-dihydroxycarbamazepine and irbesartan were proposed. And it was found that the 4 compounds, "consistent suspects" and "consistent non-targets" had similar rankings of removal rate in 16 WWTPs, which can reflect the performance of different WWTPs.