A first consideration when speaking about NORMAN’s achievements over the last 10 years is that NORMAN has been able to establish and operate a collaboration mechanism to deal with the following crucial questions about emerging substances: What are the most suitable techniques and strategies to identify and prioritize potential problematic chemicals? Do we have enough data to assess the risks associated with CECs? Do the data pass quality criteria and are they representative enough? And do we have access to all the data that are available?
Prioritization of CECs
The prioritization of chemical contaminants is a task of primary importance for environmental managers and the scientific community, for the definition of priority actions for pollution prevention and control, and the efficient allocation of resources to address current knowledge gaps. Starting from the observation that, for most emerging substances, it is primarily the knowledge gaps which still prevent proper risk assessment and risk ranking, NORMAN has developed a rational and holistic prioritization approach (Fig. 2) which gives more systematic consideration to the knowledge gaps relating to emerging substances [16, 17]. The scheme has been used by NORMAN to provide recommendations to the European Commission for the prioritization of the compounds on the first European Watch List [18] and has also been adopted by regulatory agencies in France [19, 20] and in Slovakia [21].
In the light of the experience acquired, NORMAN is now committed to the further development of the current scheme with the extension of the original NORMAN list of substances (ca. 900 compounds) to a much larger list of several thousands of compounds. This goes along with the establishment of dynamic links with existing databases (such as, for example, the US EPA CompTox Chemistry Dashboard [22]) for a more powerful and systematic retrieval of supporting data for prioritization of substances, and the introduction of new indicators for better integration of the results from novel monitoring-based approaches, such as suspect and non-target screening (NTS) as well as effect-based methods (EBM) in the prioritization process. NORMAN fosters an integrative approach for the prioritization of CECs [23], which relies on three pillars: the first is EMPODAT [24], a powerful database system which has been developed to store the monitoring data collected by NORMAN members and as a tool for use by regulators and scientists alike for the prioritization of CECs. Its added value will be further increased in the future thanks to its full integration into the European Information Platform for Chemical Monitoring (IPCHEM) [4], which will improve systematic exploitation of raw monitoring data to support prioritization exercises. This is closely connected with the second pillar, the EMPODAT ECOTOX module, a platform for systematic collection and evaluation of the relevance and reliability of ecotoxicity studies which aims to become an essential tool for the European community of ecotoxicologists for the derivation and harmonization of predicted no-effect concentration (PNEC) threshold levels. NTS, the third pillar, includes recent workflows for the application and evaluation of high-resolution mass spectrometry for identification of suspects and unknowns. The results from NTS, i.e., checking presence/absence and semi-quantitative information about these compounds in a large number of samples by NORMAN partners in different countries, will help in the future to prioritize the most relevant compounds for possible further evaluation as substances of potential regulatory concern. The collaborative NormaNEWS [25] joint activity has already successfully demonstrated the usefulness of the retrospective screening of high-resolution mass spectrometric data in establishing the spatial and temporal occurrences of newly identified compounds of potential emerging concern [26].
Data collection and data management
Reliable identification and prioritization of relevant CECs is strongly dependent on the quality and quantity of archived monitoring data. The development of databases such as EMPODAT and improvement of data exchange have been NORMAN’s core business since the start of the project. A clear need was identified at the time of the launch of the NORMAN project, which was confirmed by the first NORMAN Databases workshop in 2011 [27], where experts concluded that, in spite of the numerous chemical monitoring activities carried out in the EU and worldwide and the significant amounts of data generated by the scientific community within research projects, environmental monitoring data were not systematically collected at the EU level [28]. EMPODAT [24] is today the largest database on emerging substances worldwide, with about ten million data records for more than 500 emerging substances. The interest and contribution of the network partners have enabled the database system to constantly grow, and new modules for accommodation of passive sampling, indoor environment, bioassays monitoring, antibiotic-resistant bacteria (ARBs), and antibiotic-resistant genes (ARGs) data are now under development. Besides that, the ECOTOX module already contains predicted and experimental PNECs for more than 13,000 substances and its sustainable growth is one of the priority tasks of the NORMAN network. The trend is clearly towards encouraging data sharing, improving access and use of available data along with improvement of their quality. The value of the NORMAN platform is fully recognized by the European Commission, with which NORMAN has recently started a close collaboration to achieve permanent integration of EMPODAT in IPCHEM [4].
Evolution towards “big data” management: from hundreds to tens of thousands of candidate substances
We are increasingly aware that there is a need to evolve towards a system able to deal with several thousands of compounds which may enter the environment. NORMAN is already working to replace the original “NORMAN list of emerging substances” of about 900 compounds with a much larger list of substances. The NORMAN Suspect List Exchange database (SusDat) database [29] has recently been launched and already includes more than 40,000 compounds as a common effort of European and North American researchers. All suspect lists currently available in SusDat can be viewed at the NORMAN website and are being progressively integrated into the US EPA CompTox Chemistry Dashboard [22]. This large list will become the new “universe” of compounds for prioritization, and the NORMAN List will be defined as the list of top priority compounds in each prioritization action category.
Non-target screening analysis, combined with the integration of high-performance computing, becomes “ready to go” for environmental applications [30] and moves traditional exposure analysis to ‘big data’: the NORMAN ‘Digital Sample Freezing Platform (DSFP)’ is currently under development to host in a harmonized format full-scan high-resolution mass spectrometry (HR-MS) data, allowing for high-throughput processing (including retrospective analysis) of any environmental sample for a wide range (thousands) of pollutants. The concept of collaborating in one DSFP and sharing its ‘big data’ has been recently tested among a core group of NORMAN, with data sets obtained within the Joint Danube Survey 3 (surface water samples) [31] and the EU/UNDP EMBLAS project (marine water, sediment, and biota samples) [32]. Further improvement of functionalities of the DSFP (upload of raw mass chromatograms, visualisation of data, batch mode processing, use of MS–MS information, etc.), the extension of its functionalities for archiving and processing of gas chromatography–HR-MS data and testing of various options for archiving and processing of ‘big data’ at the wider European scale are planned for 2018 and beyond.
Methods’ harmonization and validation
The NORMAN community is recognized as particularly strong in analytical matters and the studies organized by the network represent a crucial step for the scientific community and for environmental agencies in the preparation of the ground for validation and harmonization of innovative sampling and monitoring tools before their possible future implementation in regulations.
As regards improvement of data quality, one major achievement of NORMAN has been the development of a common framework for validation of chemical and biological monitoring methods—a protocol which is now adopted as a Technical Specification (TS) of the European Committee for Standardization (CEN) (CEN TS 16800:2015) [33, 34]. In other words, NORMAN has defined a clear list of “rules” that the laboratories need to observe to be able to state that their method is “validated”—and it is well known how method validation is crucial, especially when it comes to the measurement of substances which laboratories are not familiar with, with clear consequences for the quality and reliability of the results produced. Besides that, NORMAN has organized interlaboratory studies on substances of priority interest in research [35, 36] and has more recently extended these inter-comparison activities to passive sampling [37], bioassays [38], and non-target screening methods [31].
New tools to improve future monitoring and regulation of CECs
Non-target screening
In line with the strong expertise of the NORMAN network in the field of high-resolution mass spectrometry techniques and NTS approaches, several activities have been launched over the past years and continue to be promoted to improve harmonization of liquid chromatography coupled to high-resolution tandem mass spectrometry [LC–HR-MS(MS)] and gas chromatography coupled to mass spectrometry (GC–MS) NTS protocols, in connection with the use of structure elucidation and pollution pattern recognition tools. Besides the Suspect List Exchange database [29] and the “Digital Sample Freezing Platform” [39], the NORMAN MassBank database [40, 41] was created in 2011 as an open-access database of mass spectra which now contains spectra of more than 1000 environmental contaminants to support the identification of “unknowns” (i.e., compounds with an unidentified chemical structure). A Collaborative Trial (CT) was organized for the first time worldwide in 2013 to study laboratories’ common practices and promote harmonized terminology, workflows, and reporting formats for the use of non-target and suspect screening in the area of environmental analysis [31]. Another key action was the development of a harmonized model for the prediction of the retention time index (RTI) for NTS and retrospective analysis of a large number of potential emerging substances [42, 43]. The NORMAN RTI has already been incorporated into the DSFP and it is expected that it will also soon be included in the open mass spectral libraries such as MassBank [40], STOFF-IDENT [44], and related platforms (e.g., FOR-IDENT [45]).
Effect-based tools
Bioassays are the only currently available methods able to respond to the recently recognized need to address unknown mixture risks present in the water bodies, which can then be related to specific chemical compounds via chemical analysis: instead of measuring a limited list of target individual substances known to be responsible for a given effect, it makes more sense to measure all substances (target substances plus other unknowns) that may contribute to that effect [46]. The EU Water Directors recently supported the proposal by the Commission to consider such a more holistic approach for regulation of chemicals in the aquatic environment in view of the WFD review [47] and an effect-based methods (EBM). Activity was launched as part of the CIS-WFD Programme in 2017 [48]. The successful introduction of these tools in environmental monitoring programs in the future will, however, depend on the successful transition from the current system to a new European framework defining the performance criteria for the selection of bioassays to be applied, and the QA/QC criteria for validation of the results obtained with these new methods, the effect-based trigger (EBT) values necessary for the interpretation of the data, and the way to proceed when an EBT is exceeded. NORMAN is actively contributing to this process, helping the construction of a common position of the European experts on the use of bioassays in the regulatory framework of the WFD and, more recently, in the drafting of the EU policy instrument for Water Reuse. Besides the interlaboratory study organized in 2009 to assess the comparability of results obtained with a battery of bioassays [38], NORMAN has contributed to the estrogen-monitoring project which has recently provided concrete demonstration data about the performance of the tested effect-based methods [49]. A comprehensive in-depth overview of effect-directed analysis (EDA)—the approach of choice to provide information on the compounds causing the observed effects—has been published by the respective NORMAN Working Group to meet the increasing demands for its most efficient application [11].
NORMAN supports the implementation of effect-based monitoring tools in water-quality assessment [50]. The integration of effect-based tools and ‘comprehensive’ NTS techniques has the potential to result in a more robust identification of priority CECs. In this context, EDA may be established in the future as part of the protocol to be applied at the sites where effect-based trigger values are exceeded. As an advanced screening tool, instead of time-consuming fractionation followed by effect tests and NTS, effect-based results and NTS data of whole samples can be integrated via the application of multivariate analysis (virtual EDA approach), to find correlations between effects and typical contamination patterns [43].
Passive sampling
NORMAN promotes the use of passive sampling tools, inter alia to address the current lack of temporal representativeness in water body monitoring and as a supplement to biota monitoring [10, 51].
The interest of NORMAN in passive sampling techniques started as early as 2009 with the organization of a large international interlaboratory study to assess the applicability of passive sampling for the monitoring of several groups of emerging aquatic pollutants, including pharmaceuticals, pesticides, steroid hormones, brominated diphenyl ethers, and PFOA/PFOS [10, 37]. The study showed that the passive sampling process caused less variability in results than the laboratory analysis and the translation of passive sampling data into water concentrations. A need was identified for improving the accuracy of analysis and calibration of adsorption-based passive samplers, as well as for more confidence in practical application of partition-based passive samplers.
Further actions were then organized by NORMAN [52,53,54] to investigate how environmental quality standards (EQS) values relate to results obtained from passive sampling and vice versa and to clarify where passive sampling could fit into the schemes that are currently applied for assessment of the chemical and ecological status of water bodies under the WFD [51].
Today, it is well recognized that there is a strong potential to use passive sampling tools for regulatory purposes, in particular as regards the use of these devices in concert with chemical monitoring in biota to support the chemical status assessment in European water bodies [54, 55].
To increase the relevance of passive sampling in this context, data sets based on concurrent passive sampling and biota monitoring are strongly needed. Such data sets may need to be developed at the European level and there is an opportunity for NORMAN members to contribute to federating national on-going initiatives (such as the large demonstration project organized by AQUAREF in France in 2018–2019), to similar studies in other European countries. This would facilitate the knowledge exchange and harmonization of methodology for better comparability of data at European scale.
To allow the use of passive sampling data for regulatory monitoring, it is also important to prepare the basis for archiving the generated data in appropriate databases in a harmonized format. Here, the contribution of NORMAN experts has resulted in harmonized guidelines for reporting of data obtained by passive sampling tools [NORMAN Data Collection Templates (DCTs)], which is expected to facilitate the wider exchange of monitoring data obtained with passive samplers [43]. Based on these standardized DCTs, a prototype online database module for passive sampling data has recently been developed and tested with JDS3 data [56] within the SOLUTIONS project [57].
Additional perspectives arise when considering the opportunities offered by the combination of passive sampling and non-target and suspect screening procedures. Relatively little work has been undertaken in this area until now. A suitable choice of polymer and extraction protocol can enable the scientist to pre-concentrate chemicals from a complex matrix while leaving behind a significant proportion of unwanted matrix affecting the performance of the analysis. This is especially relevant for complex matrices such as sediments, sludge, or biological matrices. Passive sampling of air, sediments, and water is amenable to non-target approaches, and novel applications for sampling of biota [58, 59] or to further our understanding of the human exposome are highly promising [60]. NORMAN, through its cross-working group activities on passive sampling and non-target screening, is ideally suited for leading this work.
Other areas of concern that NORMAN is exploring
Nano- and micro-scale particulate contaminants
The steeply increasing production volumes of engineered nanomaterials as well as incidental and natural particulate contaminants will eventually lead to a proliferation of these materials in the environment, with poorly understood effects on ecosystems. NORMAN aims to contribute to increased understanding of particle behavior in the environment and the resulting consequences for ecosystems.
To that end, NORMAN activities address the fate and transformation of particulate contaminants in natural (e.g., freshwater, floodplains, and marine systems) and technical (wastewater treatment and sewage treatment) systems. NORMAN will keep working to develop analytical methods (including sampling, sample preparation, e.g., particle extraction, clean-up, and analytical tools to detect, quantify, and characterize particulate contaminants in complex matrices) [61]. Finally, NORMAN will contribute as a platform facilitating access to research infrastructure and promoting exchanges of methods and materials.
In 2016, the NORMAN members decided to add microplastics as a new issue under the scope of the NORMAN activities [62]. NORMAN expertise in, e.g., data management, method development, and harmonization is expected to contribute to improve the assessment of plastic particles in the environment.
Wastewater reuse
A series of actions are currently being taken by the Commission to promote the reuse of treated wastewaters, including a legislative proposal on minimum requirements for reused water, e.g., for irrigation and groundwater recharge [63]. However, a number of questions are still open and they are crucial to prevent and manage health and environmental risks. Important challenges are, amongst others, associated with the presence of non-regulated contaminants, whose environmental fate and long-term effects are not yet fully understood. Moreover, the threat posed by the spread of antibiotic-resistant bacteria and the multiple evidences that domestic wastewater is amongst their major environmental reservoirs raise key questions that the scientific community is committed to answer. Today, there is a consensus that reclaimed wastewater releases antibiotic-resistant bacteria and their genes. There is, therefore, an urgent need for better understanding of the presence and fate of micro-contaminants promoting the widespread of antibiotic-resistant bacteria and genes in wastewater treatment plant (WWTPs) effluents before their disposal or further reuse [64].
In response to these needs, a new NORMAN activity kicked off in 2013 [65] with the commitment to work on: (1) the definition and establishment of a harmonized protocol for measurement of antimicrobial resistance; (2) the development of a European database to compile information on the overall abundance and diversity of different genetic determinands in wastewater effluents and receiving environments; and (3) the drafting of recommendations to the European Commission [64].
Two screening campaigns of selected ARGs were organized in 2014 and in 2015 on a representative set of WWTPs around Europe and Mediterranean countries [66]. Besides the contribution of these campaigns to the assessment of differences in the abundance and diversity of ARGs over distinct municipal wastewater treatment plants and geographic areas, a major follow-up of this study was the on-going work of the NORMAN experts on the definition of a harmonized protocol and interlaboratory calibration criteria to support a reliable ARG quantification. This is essential to assess the degree of ARG occurrence and environmental contamination, and it has never been done before. Currently, there is no baseline on the prevalence of resistance genes in aquatic (natural) environments and, to obtain this baseline, standardized protocols are pivotal. Such a baseline and a better process understanding (and corresponding models) will help to assess the potential risk of antibiotic resistances in the aquatic environment and water reuse.
Through its activities and collaborations with other relevant EU-funded projects (NEREUS [67] and ANSWER [68]), NORMAN developed in 2017 a new Data Collection Template used as a basis for a new EMPODAT database module concerning ARBs and ARGs which will be fed by this project.
Indoor environment
There is potential for extending the scope of NORMAN activities to other environmental matrices and compartments (air, sediments, biota, etc.). Indoor environment appears as a relevant key domain for NORMAN’s missions when looking at the concerns associated with emerging contaminants in human matrices. Articles and consumer products used indoors may contain a variety of both well-known chemicals and emerging substances [69,70,71]. Chemicals are emitted in the indoor environment and indoor air and dust is an important pathway of chemical exposure for humans. A new NORMAN activity for the indoor environment was launched in 2014 aimed at identifying CECs for the indoor environment and at storing respective data in a harmonized way in EMPODAT. Measuring goes along with prioritization of relevant compounds in the indoor environment, the identification of emission sources of CECs, and relevant exposure pathways. The ultimate goal of this working group is to raise awareness of CECs in indoor environments and possibly to contribute to development of new EU legislation regulating the occurrence of CECs in the indoor environment [72].
A workshop on “Emerging pollutants in non-industrial indoor environments” was organized in June 2015 at NILU, Norway to mark the first actions of NORMAN in this field [72]. Further to the workshop various activities have already been organized by NORMAN in the field of CECs in the indoor environment.
A collaborative trial on non-target and suspect screening of indoor dust was launched in 2016 for the identification of pollutants specific to indoor environments, which provides relevant input for harmonization of practices and for the definition of a list of CECs relevant for indoor environment and their prioritization. Strategies for prioritization of CECs indoors are currently being discussed and a subgroup for this task has recently been formed, in connection with the already operational NORMAN Prioritization Working Group.
The generation of high quality and comparable monitoring data—still scarce and highly scattered in the indoor environment—and minimum quality requirements for their harmonized storage in a common database is crucial to support prioritization activities. Thanks to NORMAN activities, a new Data Collection Template with relevant metadata for indoor air and dust has been developed for the indoor environment module of the NORMAN EMPODAT database.
Finally, NORMAN is committed to improving harmonization of sampling protocols for dust and air. The NORMAN indoor environment working group made a first inventory of sampling protocols used to collect indoor dust and air. The use of different sampling protocols can result in different particle size fractions collected and hence in differences in concentrations of SVOCs. There is, therefore, a great need for an inter-comparison study of different dust sampling protocols, and the setting-up of a comparison study within NORMAN for sampling protocols of dust has been proposed for 2018.