Due to the increasing number of chemicals released into the environment, nontarget screening (NTS) analysis is a necessary tool for providing comprehensive chemical analysis of environmental pollutants. However, NTS workflows encounter challenges in detecting both known and unknown pollutants with common chromatography high-resolution mass spectrometry (HRMS) methods. Identification of unknowns is hindered by limited elemental composition information, and quantification without identical reference standards is prone to errors. To address these issues, we propose the use of inductively coupled plasma mass spectrometry (ICP-MS) as an element-specific detector. ICP-MS can enhance the confidence of compound identification and improve quantification in NTS due to its element-specific response and unambiguous chemical composition information. Additionally, mass balance calculations for individual elements (F, Br, Cl, etc.) enable assessment of total recovery of those elements and evaluation of NTS workflows. Despite its benefits, implementing ICP-MS in NTS analysis and environmental regulation requires overcoming certain shortcomings and challenges, which are discussed herein.

This study aimed to investigate the spatial distribution of micropollutants in wastewater related to catchment area, and their environmental risks and fate. About 24-h flow proportional effluent (n = 26) wastewater samples were collected from eight WWTPs across Denmark. From five of these WWTPs corresponding influent samples (n = 20) were collected. Samples were enriched by multi-layer solid phase and analysed by liquid chromatography-high-resolution mass spectrometry and comprehensive two-dimensional gas chromatography with high-resolution mass spectrometry detection. We detected and quantified 79 micropollutants from a list of 291 micropollutants in at least one influent or effluent wastewater sample. From this we found that 54 micropollutants decreased in concentrations during wastewater treatment, while O-desmethylvenlafaxine, carbamazepine, amitriptyline, benzothiazole, terbutryn, and citalopram increased in concentrations through the WWTP.The toxicity of effluent wastewater samples was assessed by EC50 using Raphidocelis subcapitata (R. subcapitata) and LC50 using the crustacean Daphnia magna (D. Magna), for which six micropollutants were detected above the predicted no-effect concentration. Our study demonstrates that catchment area influences the micropollutant composition of wastewater. Out of 19 pharmaceuticals, the measured concentration in influent wastewater was predicted within a factor of 10 from sale numbers and human excretion, which demonstrates the strong influence of catchment area on micropollutant composition.

Chemical pollution caused by synthetic organic chemicals at low concentrations in the environment poses a growing threat to the ecological status of aquatic ecosystems. These chemicals are regularly released into surface waters through both treated and untreated effluents from wastewater treatment plants (WWTPs), agricultural runoff, and industrial discharges. Consequently, they accumulate in surface waters, distribute amongst environmental compartments according to their physicochemical properties, and cause adverse effects on aquatic organisms. Unfortunately, there is a lack of data regarding the occurrence of synthetic organic chemicals, henceforth micropollutants, in South American freshwater ecosystems, especially in Chile. To address this research gap, we present a comprehensive dataset comprising concentrations of 153 emerging chemicals, including pesticides, pharmaceutical and personal care products (PPCPs), surfactants, and industrial chemicals. These chemicals were found to co-occur in surface waters within Central Chile, specifically in the River Aconcagua Basin. Our sampling strategy involved collecting surface water samples from streams and rivers with diverse land uses, such as agriculture, urban areas, and natural reserves. For sample extraction, we employed an on-site large-volume solid phase extraction (LVSPE) device. The resulting environmental extracts were then subjected to wide-scope chemical target screening using gas chromatography and liquid chromatography high-resolution mass spectrometry (GC- and LC-HRMS). The dataset we present holds significant value in assessing the chemical status of water bodies. It enables comparative analysis of pollution fingerprints associated with emerging chemicals across different freshwater systems. Moreover, the data can be reused for environmental risk assessment studies. Its utilisation will contribute to a better understanding of the impact and extent of chemical pollution in aquatic ecosystems, facilitating the development of effective mitigation strategies.

Persistent, mobile, and toxic (PMT) substances are affecting the safety of drinking water and are threatening the environment and human health. Many PMT substances are used in industrial processing or consumer products, but their sources and emissions mostly remain unclear. This study presents a long-term source distribution and emission estimation of melamine, a high-production-volume PMT substance of emerging global concern. The results indicate that in China, approximately 1858.7 kilotonnes (kt) of melamine were released into the water (∼58.9%), air (∼27.0%), and soil systems (∼14.1%) between 1995 and 2020, mainly from its production and use in the decorative panels, textiles, and paper industries. The textile and paper industries have the highest emission-to-consumption ratios, with more than 90% emissions per unit consumption. Sewage treatment plants are the largest source of melamine in the environment for the time being, but in-use products and their wastes will serve as significant melamine sources in the future. The study prompts priority action to control the risk of PMT substances internationally.

Non-targeted analysis (NTA) has emerged as a valuable approach for the comprehensive monitoring of chemicals of emerging concern (CECs) in the exposome. The NTA approach can theoretically identify compounds with diverse physicochemical properties and sources. Even though they are generic and have a wide scope, non-targeted analysis methods have been shown to have limitations in terms of their coverage of the chemical space, as the number of identified chemicals in each sample is very low (e.g., ≤5%). Investigating the chemical space that is covered by each NTA assay is crucial for understanding the limitations and challenges associated with the workflow, from the experimental methods to the data acquisition and data processing techniques. In this review, we examined recent NTA studies published between 2017 and 2023 that employed liquid chromatography-high-resolution mass spectrometry. The parameters used in each study were documented, and the reported chemicals at confidence levels 1 and 2 were retrieved. The chosen experimental setups and the quality of the reporting were critically evaluated and discussed. Our findings reveal that only around 2% of the estimated chemical space was covered by the NTA studies investigated for this review. Little to no trend was found between the experimental setup and the observed coverage due to the generic and wide scope of the NTA studies. The limited coverage of the chemical space by the reviewed NTA studies highlights the necessity for a more comprehensive approach in the experimental and data processing setups in order to enable the exploration of a broader range of chemical space, with the ultimate goal of protecting human and environmental health. Recommendations for further exploring a wider range of the chemical space are given.

UNASSIGNED: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for \"suspect screening\" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.
UNASSIGNED: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA\'s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).
UNASSIGNED: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the \"one substance, one assessment\" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
UNASSIGNED: The online version contains supplementary material available at 10.1186/s12302-022-00680-6.

Parabens are one of the most widely used preservatives in food, pharmaceuticals and personal care products (PCPs) because of their advantageous properties and low toxicity based on the early assessments. However, recent research indicates that parabens may act as endocrine-disrupting chemicals (EDCs) and thus, are considered as chemicals of emerging concern that have adverse human health effects. To provide the basis for future human health studies, we reviewed relevant literature, published between 2005 and 2020, regarding the levels of parabens in the consumer products (pharmaceuticals, PCPs and food), environmental matrices and humans, including susceptible populations, such as pregnant women and children. The analysis showed that paraben detection rates in consumer products, environmental compartments and human populations are high, while the levels vary greatly by country and paraben type. The concentrations of parabens reported in pregnant women (~20-120 μg/L) were an order of magnitude higher than in the general population. Paraben concentrations in food and pharmaceuticals were at the ng/g level, while the levels in PCPs reached mg/g levels. Environmental concentrations ranged from ng/L-μg/L in surface waters to tens of μg/g in wastewater and indoor dust. The levels of human exposure to parabens appear to be higher in the U.S. and EU countries than in China and India, which may change with the increasing production of parabens in the latter countries. The review provides context for future studies to connect paraben exposure levels with human health effects.

An essential step in human biomonitoring or molecular epidemiology programs is to estimate human exposure to environmental chemicals. Despite significant progress in the capabilities of analytical methods, the number of pollutants and their metabolites keeps increasing continuously. Some of these relatively unknown chemicals of emerging concern (CECs) may pose significant health risks to humans and biota, but remain virtually undetected in traditional HBM-studies. Non-target and suspect screening techniques based on high-resolution mass spectrometry (HRMS) perform the detection and identification of compounds without any a priori compound selection or chemical information and provide a more holistic overview of human exposure. In this study, 50 urine samples (25 female and 25 male) from a larger cohort of the Flemish Environment and Health Study (FLEHS IV, 2016-2020) have been submitted to suspect screening analysis, with the aim of detecting and identifying new CECs. For this purpose, an analytical method has been developed, optimised and evaluated in terms of analytical performance. Satisfactory results were obtained in terms of reproducibility, sensitivity and quality control. Data-mining was performed through the combination of two different workflows. The use of two complementary workflows enhanced the number of identified compounds. As a result, 45 CECs have been identified with a level of confidence ranged between 3 and 1. Most of the identified compounds were metabolisation products, many of which were currently not included in the targeted measurements of FLEHS IV. The identified chemicals and metabolites could be used as candidate biomarkers of exposure in future studies. Overall, the newly developed suspect screening workflow of this pilot study provided complementary and promising results for future HBM-programs.

Chemicals of Emerging Concern (CECs) include a very wide group of chemicals that are suspected to be responsible for adverse effects on health, but for which very limited information is available. Chromatographic techniques coupled with high-resolution mass spectrometry (HRMS) can be used for non-targeted screening and detection of CECs, by using comprehensive annotation databases. Establishing a database focused on the annotation of CECs in human samples will provide new insight into the distribution and extent of exposures to a wide range of CECs in humans.
This study describes an approach for the aggregation and curation of an annotation database (CECscreen) for the identification of CECs in human biological samples.
The approach consists of three main parts. First, CECs compound lists from various sources were aggregated and duplications and inorganic compounds were removed. Subsequently, the list was curated by standardization of structures to create \"MS-ready\" and \"QSAR-ready\" SMILES, as well as calculation of exact masses (monoisotopic and adducts) and molecular formulas. The second step included the simulation of Phase I metabolites. The third and final step included the calculation of QSAR predictions related to physicochemical properties, environmental fate, toxicity and Absorption, Distribution, Metabolism, Excretion (ADME) processes and the retrieval of information from the US EPA CompTox Chemicals Dashboard.
All CECscreen database and property files are publicly available (DOI: https://doi.org/10.5281/zenodo.3956586). In total, 145,284 entries were aggregated from various CECs data sources. After elimination of duplicates and curation, the pipeline produced 70,397 unique \"MS-ready\" structures and 66,071 unique QSAR-ready structures, corresponding with 69,526 CAS numbers. Simulation of Phase I metabolites resulted in 306,279 unique metabolites. QSAR predictions could be performed for 64,684 of the QSAR-ready structures, whereas information was retrieved from the CompTox Chemicals Dashboard for 59,739 CAS numbers out of 69,526 inquiries. CECscreen is incorporated in the in silico fragmentation approach MetFrag.
The CECscreen database can be used to prioritize annotation of CECs measured in non-targeted HRMS, facilitating the large-scale detection of CECs in human samples for exposome research. Large-scale detection of CECs can be further improved by integrating the present database with resources that contain CECs (metabolites) and meta-data measurements, further expansion towards in silico and experimental (e.g., MassBank) generation of MS/MS spectra, and development of bioinformatics approaches capable of using correlation patterns in the measured chemical features.

Contaminants of emerging concern (CECs), such as pharmaceuticals, personal care products, and hormones, are frequently found in aquatic ecosystems around the world. Information on sublethal effects from exposure to commonly detected concentrations of CECs is lacking and the limited availability of toxicity data makes it difficult to interpret the biological significance of occurrence data. However, the ability to evaluate the effects of CECs on aquatic ecosystems is growing in importance, as detection frequency increases. The goal of this study was to prioritize the chemical hazards of 117 CECs detected in subsistence species and freshwater ecosystems on the Grand Portage Indian Reservation and adjacent 1854 Ceded Territory in Minnesota, USA. To prioritize CECs for management actions, we adapted Minnesota Pollution Control Agency\'s Aquatic Toxicity Profiles framework, a tool for the rapid assessment of contaminants to cause adverse effects on aquatic life by incorporating chemical-specific information. This study aimed to 1) perform a rapid-screening assessment and prioritization of detected CECs based on their potential environmental hazard; 2) identify waterbodies in the study region that contain high priority CECs; and 3) inform future monitoring, assessment, and potential remediation in the study region. In water samples alone, 50 CECs were deemed high priority. Twenty-one CECs were high priority among sediment samples and seven CECs were high priority in fish samples. Azithromycin, DEET, diphenhydramine, fluoxetine, miconazole, and verapamil were high priority in all three media. Due to the presence of high priority CECs throughout the study region, we recommend future monitoring of particular CECs based on the prioritization method used here. We present an application of a chemical hazard prioritization process and identify areas where the framework may be adapted to meet the objectives of other management-related assessments.