(2020) 32:100
Dulio et al. Environ Sci Eur
https://doi.org/10.1186/s12302-020-00375-w

Open Access

COMMENTARY

The NORMAN Association and the European
Partnership for Chemicals Risk Assessment(PARC): let’s cooperate!
Valeria Dulio1* , Jan Koschorreck2*, Bert van Bavel3, Paul van den Brink4, Juliane Hollender5,John Munthe6, Martin Schlabach7, Reza Aalizadeh11, Marlene Agerstrand9, Lutz Ahrens10, Ian Allan3,
Nikiforos Alygizakis8,11, Damia’ Barcelo’12, Pernilla Bohlin‑Nizzetto7, Susanne Boutroup13, Werner Brack14,15,
Adèle Bressy16, Jan H. Christensen17, Lubos Cirka8, Adrian Covaci18, Anja Derksen19, Geneviève Deviller20,
Milou M. L. Dingemans21,22, Magnus Engwall23,24, Despo Fatta‑Kassinos25, Pablo Gago‑Ferrero26,
Félix Hernández27, Dorte Herzke7, Klára Hilscherová28, Henner Hollert15, Marion Junghans29,
Barbara Kasprzyk‑Hordern30, Steffen Keiter24, Stefan A. E. Kools21, Anneli Kruve9, Dimitra Lambropoulou31,
Marja Lamoree32, Pim Leonards32, Benjamin Lopez33, Miren López de Alda12, Lian Lundy34,50,
Jarmila Makovinská35, Ionan Marigómez36, Jonathan W. Martin9, Brendan McHugh37, Cécile Miège38,
Simon O’Toole39, Noora Perkola40, Stefano Polesello41, Leo Posthuma42,43, Sara Rodriguez‑Mozaz26,
Ivo Roessink4, Pawel Rostkowski7, Heinz Ruedel44, Saer Samanipour45, Tobias Schulze14, Emma L. Schymanski46,
Manfred Sengl47, Peter Tarábek35, Dorien Ten Hulscher48, Nikolaos Thomaidis11, Anne Togola33, Sara Valsecchi41,
Stefan van Leeuwen4, Peter von der Ohe2, Katrin Vorkamp49, Branislav Vrana28 and Jaroslav Slobodnik8*†

Abstract
The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innova‑
tion programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemi‑
cal risk assessors and managers together with scientists to accelerate method development and the production ofnecessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a
non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established andcompetent network of more than 80 organisations in the field of emerging substances and has enormous potential
to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to
PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation tochemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contami‑
nants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In
this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the*Correspondence: valeria.dulio@ineris.fr; jan.koschorreck@uba.de;slobodnik@ei.sk†
1
INERIS, National Institute for Environment and Industrial Risks, Verneuilen Halatte, France
2
UBA, Federal Environment Agency, Dessau‑Roßlau, Germany
8
Environmental Institute, Koš, Slovakia
Full list of author information is available at the end of the article© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) andthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material
in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material
is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds thepermitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat​iveco​
mmons​.org/licen​ses/by/4.0/.

Dulio et al. Environ Sci Eur(2020) 32:100

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PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging
concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis
tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks
to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge andexperience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step
towards the goal of a non-toxic environment can be taken.
Keywords: NORMAN network, Suspect screening, Non-target screening, Contaminants of emerging concern,
Environmental monitoring, High-resolution mass spectrometry, Effect-based methods, Chemical risk assessment andprioritisation

Background
The PARC partnership is currently under development
as a joint research and innovation programme to support the European Commission (EC) and national
chemical risk assessment and management authorities by providing new evidence and methodologies andpromoting their uptake in regulatory processes. Thisapplies to currently recognised as well as potential
future contaminants of emerging concern (CECs).
Over the past 15 years, the NORMAN Association
has developed a network of expert organisations in thefield of CECs in the environment. This effort fits wellwith the aims and structure of the PARC initiative [1]for a European Partnership for Chemicals Risk Assessment. It is therefore no surprise that NORMAN fully
supports the “evolution, not revolution” principle of
the PARC initiative, and agrees that existing data andmethods should be integrated and further developed
without “reinventing the wheel”, as we explain in moredetail in this paper.
In the PARC partnership, the plan is to join forces
with scientists to create the next generation of chemicalrisk assessment and to facilitate ‘The European Green
Deal’ [2], which includes the sustainable managementof chemicals for a non-toxic environment. An essential
role of this partnership is to foster better use of existing knowledge and data, and better cooperation andcoordination of research on the regulatory needs—allin order to improve risk assessment and management,
including the development of an EU early warning system for emerging risks of chemicals in the environment.
The European Commission acknowledges the importance of continuously improving knowledge about the(eco)toxicity of chemicals and of adequately addressing
uncertainties regarding exposure to chemicals [3, 4].
Moreover, current regulations are not sufficiently effective to tackle CECs and chemical risks in general, sincea holistic view is missing and there are often inconsistencies between different use sectors [5]. The vision
for future chemicals policy is that chemicals should be
dealt with in an integrated manner in an overarchingchemicals policy framework covering all types of chemicals and all uses, beyond the current sector-specificregulations.
It is in this context that the NORMAN network cameinto existence in 2005 as a project, following a call by
the EC (DG Research) aimed at creating a permanent
platform to reduce knowledge gaps and better meet therequirements of risk assessors and risk managers concerning CECs [6]. NORMAN is today an independent,
self-funded, non-profit, multidisciplinary and multinational association in the field of CECs in the environment, which brings together more than 80 organisations
representing various stakeholders, including competentauthorities, national reference laboratories, research centres, academia and industry—mostly in Europe, but alsoin North America and Asia [7].
The missions of NORMAN are to: (i) facilitate a more
rapid and wider exchange of data on the identity, occurrence and effects of CECs in water, biota, air, soil andindoor environment; (ii) improve data quality and comparability via validation and harmonisation of common
sampling and measurement methods (chemical andbiological), and (iii) provide tools for the risk and hazard assessment of CECs [6]. Since the primary objectiveof the NORMAN Association is to act as a science-topolicy interface, the outcomes of the network’s activities are regularly shared with the EC’s services including
DG Environment, European Chemicals Agency (ECHA),
European Environment Agency (EEA), EC Joint ResearchCentre (JRC), international river commissions, regionalsea conventions and national regulatory bodies. Currently, nine national regulatory agencies are members of
the NORMAN Association.
The NORMAN Association has considerable—andcontinuously developing—experience of establishing: (i) aconsolidated network of closely cooperating laboratories
active in research to support chemical risk assessmentand management; (ii) a joint, user-friendly and openaccess data space to share knowledge on CECs in theenvironment and promote harmonised protocols for datacollection and reporting; (iii) a collaborative framework

Dulio et al. Environ Sci Eur(2020) 32:100

to foster validation and harmonisation of measurement methods and monitoring tools; (iv) advanced data
analysis tools to deal with less-investigated substancesin support of a European early warning system to detect
emerging chemical risks to the environment, and (v) asystem for harnessing, combining and sharing expertiseamong research teams, national reference laboratories
and environmental agencies in innovative methods insupport of chemical risk assessment. So far, NORMAN
has been strongly involved in CECs in the fresh wateraquatic environment and the associated EU policies. The
focus has recently extended beyond fresh water to theindoor, marine, soil and terrestrial environments andwater reuse, while the scope of CECs is also expanding
to include additional parameters such as antibiotic resistance determinants and microplastics.
In this opinion paper we would like to highlight thetools developed by NORMAN that we consider most relevant to support the PARC initiative.

Joint data space and cutting‑edge research tools
for risk assessment of contaminants of emerging
concern
NORMAN Database System (NDS): data gathering and data
management
Perspective and recommendations

Continue to develop the NORMAN Database System(NDS) as a reference database that brings together, in asingle platform, widely differing chemical monitoringdata acquired using various techniques and in different matrices, thereby ensuring a harmonised approachfor data collection, storage, quality control, curation andexchange among NORMAN members and more widely.
Future platform development will be guided by the FAIR
principles (Findability, Accessibility, Interoperability, andReuse of data).
The NDS is complementary to the EC Information
Platform for Chemical Monitoring (IPCHEM) [8, 9] inharvesting chemical target monitoring data, while at thesame time paving the way for the development of a new
European infrastructure for handling data coming frominnovative methods, such as non-target screening (NTS)
and effect-based methods (EBM). It should continue inthat role.
Rationale

The crucial task of gathering and managing environmental CEC exposure data to support chemical risk
assessment has been the core activity of the NORMAN
Association from its start in 2005.
The current NDS [10] is an open-access platform ofinterconnected databases able to assist effective andPage 3 of 11

rapid screening and risk assessment of contaminants inthe environment.
The unique feature of the NDS is that it provides a comprehensive set of data on CECs together with a range ofinnovative applications for their hazard and risk assessment. These tools range from physico-chemical properties, use characteristics, mass spectral information, andexposure data from target and non-target screening inall environmental compartments, to ecotoxicity dataand in situ bioassay signals reflecting mixture toxicity.
The NDS currently consists of 12 modules (Fig. 1), of
which eleven (Substance Database (SusDat); Suspect List
Exchange (SLE); Chemical Occurrence Data (EMPODAT); Ecotoxicology; Bioassays Monitoring Data; MassBank Europe; Digital Sample Freezing Platform (DSFP);
Indoor Environment; Passive Sampling; Substance
Factsheets; Prioritisation) are accessible, interlinked andpopulated with data. The 12th is an antibiotic-resistant bacteria and genes module (ARB&ARG) that is still
under development, while a new module hosting data on
microplastics is currently being designed.
A selection of the NDS modules most relevant to PARC
is presented below.
NORMAN Substance Database: a common listof substances for harmonised chemical risk assessment
Perspectives and recommendations

Further develop the Substance Database (SusDat) as
the cornerstone of a common European platform where
information on highly relevant and newly discovered
environmental pollutants can be shared in a harmonised
format [11].
Rationale

A common, harmonised list of chemical compounds
shared among all parties in research and regulation is one
critical requirement for enhanced cooperation among
existing regulatory frameworks and shifting towards
a “one chemical, one assessment” paradigm. However,current chemicals lists are fragmented collections, withresearchers and regulators all using their own lists.
We believe that the combination of NORMAN Suspect List Exchange (SLE) [12] and the merged NORMAN
Substances Database [13] of the NDS could be a globallyleading model for collaboratively working towards such alist. Numerous organisations, national and international
regulatory agencies and research groups from Europe
and North America already contribute to this initiative.
NORMAN SLE is a platform to share lists of substances
potentially responsible for emerging risks to ecosystems
and human health. The submitted lists are shared with
US EPA CompTox Chemicals Dashboard [14, 15] andPubChem [16, 17] and are published on Zenodo [18]. By

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Fig. 1 The NORMAN Database System (NDS)

acting as a data collector, the NORMAN SLE has become
an important source of specialised research information for major chemical databases such as PubChem and
CompTox, beyond the realms and means of individual
researchers. In return, the integration of the NORMAN
SLE into major chemical databases adds enormous value
to the original contributions, offering up new functionality for all parties.
The merged list (without duplicates) is known as
NORMAN SusDat [13]—a curated compound database(65,697 compounds as of April 2020), where substances
are merged by the Standard InChIKey, which acts as theunique identifier. This is accompanied by other structural information such as CAS numbers and SMILES,
as well as physico-chemical properties. SusDat also
contains mappings to the equivalent “MS Ready” forms[19], as well as other mass spectrometric information for
the identification of compounds with NTS techniques,
estimated (in silico) Predicted No-Effect Concentrations (PNECs), and other information required for theprioritisation and risk assessment of substances. Since
2016, SusDat has been used to interlink all NORMAN
databases among themselves, as well as the NDS withmajor external databases.
NORMAN Ecotoxicology Database: a common platform
for ecotoxicity assessment
Perspectives and recommendations

Establish a core team of ecotoxicology experts, fromEU Member States and globally, using the Ecotoxicology Database as a basis to evaluate the reliability andrelevance of ecotoxicity studies and reach consensus on
Quality Standards (i.e. PNEC values) for a more harmonised risk assessment of chemicals.
Rationale

We propose to share the NORMAN Ecotoxicology Database [20] for harmonised ecotoxicity assessment within
the PARC partnership. The database provides a transparent tool to guide experts in: (i) the identification of theDulio et al. Environ Sci Eur(2020) 32:100

reliable ecotoxicity studies, based on the CRED (Criteria
for Reporting and Evaluating ecotoxicity Data) classification system [21]; (ii) the online derivation of a set of quality standards for each matrix and regulatory framework
based on selected ‘reliable’ ecotoxicity studies, using abuilt-in software tool implementing the requirementsof the EC guidelines [22], and (iii) the final selection of asingle, common PNEC value, agreed upon as a result ofEurope-wide expert consultations.
At present the database comprises, for almost all SusDat substances (i.e. >  65,000), at least one in silico PNEC
[23] based on predicted acute effects for each of the threebasic trophic levels of the fresh water compartment (fish,
daphnia, and algae), which are used when experimental
toxicity data are insufficient or not available. In 2019, asemi-automated tool for retrieving experimental (eco)toxicity data from the US EPA ECOTOX Knowledgebase allowed the import of >  125,000 experimental dataon standard (eco)toxicity endpoints for about 5000 SusDat substances in a format compatible with the metadata
requirements of the NORMAN Ecotoxicology Database.
Additional experimental (eco)toxicity data and thresholdvalues will be retrieved from other databases such as the
REACH portal, the ETOX database of the German Federal Environment Agency, as well as existing PNECs andQuality Standards (EQS) from various regulatory sources.
The (eco)toxicity threshold values used for chemicals prioritisation are agreed by experts and referred to as ‘Lowest PNECs’. These values are generally calculated for the
fresh water matrix and then converted to an equivalent
PNEC value for marine water, sediment and biota matrices (for example, bioconcentration factors (BCF) are used
for conversion to equivalent PNECs for biota).
EMPODAT: a database of target monitoring data
Perspectives and recommendations

Provide a Europe-wide standard for essential quality
information (metadata) accompanying chemical analysis
results and commonly agreed minimum requirements toallow interoperability of archived monitoring data.
Rationale

A game changer for next generation chemical risk assessment is a system able to provide comprehensive information on the exposure of humans and the environment tolarge numbers of chemicals during the entire life cycle ofproducts, including waste and recycled products.
With the EMPODAT database module [24] of the
NDS, the NORMAN Association has already establisheda collaboration with IPCHEM, the official European
repository of monitoring data produced by national monitoring programmes and EU-funded research projects
in all matrices and compartments. EMPODAT today

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hosts approximately 10.3 million geo-referenced target
monitoring data of more than 3100 substances in water(surface, ground, and waste water), sediment, biota,
soil, sewage sludge and air matrices. The data are publicly accessible and provide an overview of benchmark
values on the occurrence of contaminants of emerging
concern across Europe. From the start, NORMAN has
made a great effort to ensure that the data are gathered
in a standard format in order to facilitate data comparability and exploitation across Europe and beyond. These
spreadsheet-based Data Collection Templates (DCTs)
were developed for each of the matrices, and contain
information allowing for automated assessment of data
quality.
Non‑target screening (NTS) tools and Digital Sample
Freezing Platform (DSFP) for retrospective suspect
screening of environmental contaminants
Perspectives and recommendations

Establish a federated European infrastructure storing
raw non-target screening data converted into a common(open) format, designed for retrospective screening.
Establish a central platform/database storing regularly
updated information on available data sets Europe-wide
and, eventually, at a global scale.
Apply commonly agreed workflow(s) for retrospective
analysis to identify and prioritise pollutants frequently
detected in environmental samples.
Rationale

Thanks to NTS techniques it is possible to obtain an
overview of human and environmental exposure to thousands of chemicals simultaneously, with a high level ofsensitivity and selectivity, including chemicals that havenot been identified previously [25]. The NTS workflows(comprising wide-scope target, suspect and non-target
screening) based on full scan, high-resolution mass spectrometry (HRMS), developed by NORMAN members,
represent the state-of-the-art methods to deal with realworld contaminant mixtures in a more holistic way.
Active since 2013, the NORMAN NTS Working Grouphas built a strong collaborative infrastructure and developed innovative tools to facilitate exploitation and interpretation of complex data produced by full scan, HRMS
methods. NORMAN members have also developed protocols to implement NTS in routine, regulatory applications. Suspect screening of pre-defined lists of tens totens-of-thousands of known substances in each sample(supported by NORMAN SLE and NORMAN SusDat) ispresently the recommended way forward.
In this context the Digital Sample Freezing Platform[26] is a key tool developed by NORMAN to support
suspect and non-target screening. This novel technology

Dulio et al. Environ Sci Eur(2020) 32:100

allows the storage of thousands of high-resolution mass
spectra (fingerprints) of all chemicals, metabolites andtransformation products detected in each of the analysedsamples. Thanks to this platform, it is possible for users
to search retrospectively for a large number of compounds (e.g. those in SusDat; see above) in all the “digitally frozen” samples stored in the database and obtainreliable qualitative and semi-quantitative data on theiroccurrence in the investigated samples.
Further key tools, supported by NORMAN and embedded in the NDS, to assist non-target screening, are:• MassBank Europe, an open-source, open-accessdatabase of mass spectra to support higher confidence identification of suspects and non-targets [27,28]. Based on MassBank Japan, MassBank Europe
was founded in 2011, arising from a NORMAN
initiative. Today MassBank contains over 80,000
unique mass spectra for > 14,300 compounds (database release 2020.05 [29]), including mass spectra oftentatively identified compounds. MassBank Europe
is a core service for NORMAN as well as for otherinitiatives such as HBM4EU (Human Biomonitoring for Europe) initiative [30], ELIXIR [31], the German Network for Bioinformatics Infrastructure (de.
NBI) [32] and the German National Research Data
Infrastructure Initiative for Chemistry (NFDI4Chem)[33];• A Retention Time Index (RTI) prediction model [34,35] allowing for tentative identification of each compound in SusDat as a combination of its exact mass,
MS/MS fragments and the predicted RTI value,
reduces the number of false positives in suspect
screening.
Thanks to all the above-mentioned interconnected
tools, DSFP can provide reliable qualitative and semiquantitative data on the occurrence of already identified as well as novel CECs, thereby providing exhaustive
insight into the spatial and temporal distribution of contaminant mixtures in the environment, making NORMAN DSFP a virtual environmental observatory on
chemical contamination. Extensions of DSFP for additional chemicals captured in SusDat (e.g. highly polar
molecules and gas chromatography-only amenable substances) are under way.
Collaborative European framework to improve data quality
and comparability: development and harmonisationof methods
Perspectives and recommendations

Build the capacity of laboratories in Europe and globallyby systematic organisation of international Collaborative

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Trials addressing analysis of CECs in various matrices by
novel analytical technologies.
Pursue progressive testing and implementation of novel
sampling and analytical methodologies to help design
smart(er) monitoring strategies that can be applied inregulatory monitoring activities.
Rationale

NORMAN brings together the leading European institutions in the development and harmonisation of measurement methods for the detection of emerging chemicals in
the environment. The studies organised by the network
represent a crucial step for the scientific community andfor environmental agencies for validation and harmonisation of innovative sampling and monitoring tools before
their possible future implementation in regulations.
NORMAN is the author of the first common framework for validation of chemical and biological monitoring methods—a protocol which is now adopted as aTechnical Specification (TS) of the European Committee
for Standardization (CEN) (CEN TS 16800:2015) [36, 37].
More than 15 collaborative trials have been organised
by NORMAN since 2006 on a wide range of methods,
including non-target screening in water [38], sediment[39], indoor dust [40] and biota [41], in vitro and in vivo
bioassays [42] and passive sampling [43, 44]. They havetackled aspects relevant to monitoring and early warning of CECs in the environment and approaches to hazard assessment, including integration of effect-based
methods with chemical analysis to improve interpretation of cause–effect links. These trials included not only
the assessment of sample preparation and instrumental
performance, but also the evaluation of the impact thatcomputational and data processing tools have on interpretation of results.

Advanced data analysis tools: towards a European
Early Warning System
Prioritisation of substances and priority setting
Perspectives and recommendations

Systematically collect wide-scope target, suspect andnon-target screening data at European scale to improve
the spatial and temporal coverage and range of matrices
available for risk assessment.
Identify compounds for which robust (eco)toxicity
studies are needed as a priority.
Prioritise chemicals for which standards or mass spectra will be required from industry, to enable their detection in the environment.
Develop dynamic open-access links to spatially detailed
information about production, uses, exposure to andconsumption of chemicals.

Dulio et al. Environ Sci Eur(2020) 32:100

Develop a common European scheme for grouping ofchemicals and indicator substances, based on various
criteria including sector of use, chemical structure andmode of action.
Integrate more strongly chemical analytical and effectbased methods in order to identify effect and (mixture-)risk drivers, i.e. substances or groups of substances thatshould be selected for further risk assessment.
Rationale

In the past decade, NORMAN has developed an integrated strategy to deal with less-investigated substances
for which knowledge gaps are identified (e.g. insufficient
information on the exposure levels and/or adverse effects,
or inadequate performance of the analytical methods fortheir measurement in the environment) [45]. The concept involves the application of a decision tree whichallows the allocation of substances into six main action
categories, based on the identified knowledge gaps andactions needed to address them. The priority within eachcategory is then evaluated on the basis of specific occurrence, hazard (persistence, bioaccumulation, mobility,
endocrine disruption potential, etc.) and risk indicatorssuch as the Frequency of Exceedance (FoE) and Extent of
Exceedance (EoE) of the Lowest PNECs.
Various aspects of a categorisation/ranking system havebeen scaled up and tested in numerous large-scale European projects and national prioritisation processes suchas defining Water Framework Directive (WFD) River
Basin Specific Pollutants (RBSP) in the Danube River
Basin [46] or selecting national Watch List substances
and RBSP in France [47, 48] and in The Netherlands [49].
In this way, NORMAN aims to provide a scheme for harmonised RBSP assessment across the EU. On a regularbasis, NORMAN also makes recommendations to theCommission regarding substances to be added to the listof WFD Priority Substances and EU Watch List [50].
This workflow, originally designed to work with target
monitoring data, now integrates the automatic query of
NTS mass spectral information archived in DSFP (seeabove). Thanks to DSFP and the set of fully integrated
tools and databases developed by NORMAN, it is now
possible to obtain an overview of the state of knowledge(spatial distribution of contaminants, degree of exceedance of threshold values based on semi-quantified data,etc.) of a dynamically updated list of > 60,000 chemicals,
including many never studied before, and to identify priority substances/groups of substances for which further
actions need to be taken.
This approach fits well with the requirements of an
Early Warning System, where the data to correctly identify an emerging risk at an early stage are typically limited
or of poor quality. In this context, it is important to use

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a transparent and rational approach for signal identification and characterisation that is able to deal with theknowledge gaps that still prevent proper risk assessment
and risk ranking of most emerging substances. Individualcomponents of the Early Warning System concept, suchas NormaNEWS, have already been trialled [51].
Effect‑based methods (EBM) for monitoring of chemical
mixtures in the environment
Perspectives and recommendations

Systematically include NTS and EBM in investigative monitoring programmes to support chemicals risk
assessment.
Further develop and implement effect-based methods
in a wider range of environmental compartments, including the marine and terrestrial environments.
Harmonise, and provide training on, the use of effectbased methods.
Rationale

Bioassays are the only currently available methods able
to respond to the recently recognised need to address
unknown mixture risks present in the environment,
which can then be linked to specific chemical compounds
via chemical analysis [52, 53].
NORMAN is actively contributing to the constructionof a common position of the European experts on the useof bioassays in the regulatory framework of the WFD, inparticular with the definition of a battery of bioassays forchemical water quality assessment [54]. Besides an interlaboratory study organised in 2009 to assess the comparability of results obtained with a battery of bioassays [42]and a comprehensive literature review on the development of an ecotoxicological perspective on neurotoxicity
assessment [55], NORMAN contributed to the Science
to Policy Interface (SPI) Estrogen monitoring project (avoluntary initiative of 12 countries and 24 organisations
in Europe), which has recently provided concrete demonstration data about the performance of the tested EBM[56].
In terms of practical implementation of EBMs in theregulation, another crucial step is the determinationof effect-based trigger values (EBT), which define theacceptable level of effect for each toxicological endpointof concern and thus allow environmental managers tointerpret EBM data and distinguish between more andless polluted sites. In collaboration with the SOLUTIONS
project (FP7/603437), NORMAN has contributed to thedrafting of a proposal for a harmonised methodology forthe definition of effect-based trigger (EBT) values [57]and the way to proceed when an EBT is exceeded [58,59].

Dulio et al. Environ Sci Eur(2020) 32:100

In contrast to EQSs, EBTs consider all chemicals in a
mixture contributing to a measured effect in a given
sample. Explaining the observed activity detected by theapplied bioassays and addressing the combined effectof chemicals can be done (using mass balances/‘iceberg
modelling’) by calculation of Toxic Units (TU) for eachof the quantified pollutants or Bioanalytical Equivalentconcentrations (BEQ), depending on the bioassay. Thisshould be followed by a comparison of the estimated∑TU or BEQ from the component-based assessmentwith the TU and BEQ derived from the bioassay testing.
If EBTs are exceeded and the component-based assessment cannot explain the activity detected in the bioassay, an Effect-Directed Analysis (EDA) protocol shouldbe performed in order to identify the risk drivers [54, 60,
61].
In this context, NTS-based approaches are key toimproving the identification of risk drivers and facilitating compound/mixture prioritisation in different matrices. As a matter of fact, large datasets from non-target
screening and effect-based methods can be exploredusing multivariate statistics and pattern recognition
methods to identify peaks that co-vary with detected
effects (virtual effect-directed analysis). The NORMAN
Joint Programme of Activities promotes this type ofstudy as a way to identify candidate compounds for further investigation [41].
Finally, as part of its latest Joint Programme of Activities, NORMAN will develop a bioactivity database. This
project aims to support the interpretation of effect-based
monitoring data for mixture toxicity modelling. A richer
set of bioactivity data will be crucial to understanding
the contribution of detected chemicals to the observed
effect in the different assays. Currently, the lack of effectdata for the detected chemicals in different assays is amajor limitation and more data is needed for a significant
improvement of mixture modelling and elucidation ofdrivers of toxicity. This database will be essential to reveal
CEC-induced bioassay activity that cannot be explainedby the measured concentrations of the few individual
chemicals for which effect data are already known [41].
Other needs and purposes for this database, e.g. selectionof EBMs, are currently being explored within the NORMAN network.

Support to national and European chemical risk
assessment: harnessing, combining and sharing
evidence and expertise on CECs
Cross‑border cooperation and information exchange—
monitoring super‑sites in Europe
Perspectives and recommendations

Organise Europe-wide collaborative environmental monitoring programmes using novel analytical methodologies

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in a broad range of matrices and on selected super-sites
providing representative geographical coverage andresults directly supporting regulations.
Improve the sharing and use of local, regional, national
and EU-level monitoring data between countries andpolicy areas (e.g. legislation for environment, chemicals,
food, products, waste, etc.) and relevant institutions.
Rationale

All state-of-the-art tools presented here have beendeveloped and tested within large-scale European
projects (e.g. FP7 SOLUTIONS, EDA-EMERGE
FP7-PEOPLE-2011-ITN/290100, ANSWER H2020MSCA-ITN-2015/675530, NEREUS COST Action
ES1403, APEX LIFE17 ENV/SK/000355).
NORMAN works in close cooperation with international river basin organisations (e.g. the International
Commission for the Protection of the Danube River(ICPDR) ± 14 European countries and the EU; organising Joint Danube Surveys every 6 years), sea conventions(e.g. Black Sea Commission; OSPAR), environmental
specimen banks and environmental authorities in various
Member States (e.g. France, Germany, Nordic countries,
The Netherlands).
In 2019 the NORMAN Association received funding
from the ICPDR as a contribution in support of its participation in the experimental activities of the 4th Joint
Danube Survey (JDS4). The added value of this type ofcollaboration is the opportunity to investigate and demonstrate the capabilities and limits of new environmental
assessment frameworks with a clear link to their application in a regulatory framework.
So far, NORMAN has been strongly involved in issues
related to CECs in the fresh water cycle and the associated EU policies. In the light of NORMAN’s missions andthe need to ensure a holistic view of emerging risks associated with chemicals in the environment, the activities
are progressively being extended to the indoor, marine
and terrestrial environment and water reuse, therebybuilding on experience gained in the water compartment
to facilitate the transfer to other environmental matrices.

Conclusions
Scientific knowledge continues to progress, and novel
tools are constantly being developed. This helps competent authorities and industry in the full value chain ofchemicals to provide answers to unanswered or newly
arising questions regarding risks of chemicals to theenvironment and human health, with a particular focus
on early warning, anticipation and prevention of futurerisks.
In this paper, we have sought to provide a clear andtransparent message about how NORMAN as an

Dulio et al. Environ Sci Eur(2020) 32:100

independent, well-established and competent networkof expert organisations in the field of emerging substances has enormous potential to contribute to theimplementation of the PARC partnership by sharing
several of its existing key tools that we believe are particularly relevant to the success of the initiative.
An important role of the PARC partnership will be
to foster cooperation and better use of existing knowledge, for better coordination of research and uptake ofscientific findings in regulation.
NORMAN stands ready to provide expert advice to
PARC’s stakeholder forum, drawing on its 15 years ofexperience in the development, harmonisation andtesting of advanced tools in relation to CECs and insupport of a European Early Warning System to unravel
the risks of CECs and close the gap between researchand innovation and regulatory processes. NORMAN
is a platform for scientific cooperation building upon
voluntary member contributions to advance our knowledge and understanding of CECs in the environment.
By combining the extensive knowledge and experience of the NORMAN network with the financial andpolicy-related strengths of the PARC initiative, a large
step towards the goal of a non-toxic environment canbe taken.
Abbreviations
ARB: antibiotic-resistant bacteria; ARG​: antibiotic-resistant genes; BCF: bio‑
concentration factor; CAS: chemical Abstracts Service; CEC: contaminants ofemerging concern; CEN: European Committee for Standardization; CEN TS:
CEN Technical Specifications; CIS: Common Implementation Strategy of the
WFD; DG ENV: Directorate-General for Environment of the European Com‑mission; DG Research: Directorate General for Research and Innovation of theEuropean Commission; EBM: effect-based methods; EBT: effect-based trigger
values; EC: European Commission; ECHA: European Chemical Agency; EC
JRC: Joint Research Centre of the European Commission; EDA: effect-directed
analysis; EEA: European Environment Agency; EQS: environmental quality
standard; ICPDR: International Commission for the Protection of the Danube
River; IPCHEM: European Information Platform for Chemical Monitoring; JDS:
Joint Danube Survey; NTS: non-target screening; PNEC: predicted no-effectconcentration; RBSP: River Basin Specific Pollutants; WFD: Water Framework
Directive.
Acknowledgements
The NORMAN Association gratefully acknowledge the support of all theirmembers and collaborators over the 15 years of the association.
Authors’ contributions
VD, JK and JS have closely collaborated to write the first draft manuscript.
PvdO, ES and TS provided detailed feedback/material on specific activities. All
authors have read, made comments and approved the final manuscript.
Funding
Not applicable.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.

Page 9 of 11

Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
INERIS, National Institute for Environment and Industrial Risks, Verneuil en
Halatte, France. 2 UBA, Federal Environment Agency, Dessau‑Roßlau, Germany.
3
NIVA, Norwegian Institute for Water Research, Oslo, Norway. 4 Wageningen
University & Research, Wageningen, The Netherlands. 5 Eawag, Dübendorf,
Switzerland. 6 IVL, Swedish Environmental Research Institute, Goteborg,
Sweden. 7 NILU, Norwegian Institute for Air Research, Kjeller, Norway. 8 Envi‑ronmental Institute, Koš, Slovakia. 9 Department of Environmental Science,
Stockholm University, Stockholm, Sweden. 10 Department of Aquatic Sciences
and Assessment, SLU, Swedish University of Agricultural Sciences, Uppsala,Sweden. 11 National and Kapodistrian University of Athens, Athens, Greece.
12
CSIC, Spanish Council for Scientific Research, Barcelona, Spain. 13 DCE,
Aarhus University, Aarhus, Denmark. 14 UFZ, Helmholtz Centre for Environmen‑
tal Research, Leipzig, Germany. 15 Goethe University, Frankfurt am Main, Ger‑
many. 16 Leesu Ecole des Ponts, Univ Paris Est Creteil, Marne‑la‑Vallee, France.
17
Department of Plant and Environmental Sciences, University of Copenha‑
gen, Copenhagen, Denmark. 18 Toxicological Centre, University of Antwerp,
Wilrijk, Belgium. 19 AD eco advies, Amsterdam, The Netherlands. 20 DERACEnvironmental risk assessment of chemicals, Marseille, France. 21 KWR Water
Research Institute, Nieuwegein, The Netherlands. 22 Institute for Risk Assess‑ment Sciences, Utrecht University, Nieuwegein, The Netherlands. 23 SWACCS,
Swedish Academic Consortia for Chemical Safety, Örebro, Sweden. 24 MTM
Research Centre, Örebro University, Örebro, Sweden. 25 Department of Civil
and Environmental Engineering and Nireas‑International Research Center,
University of Cyprus, Nicosia, Cyprus. 26 ICRA, Catalan Institute for Water
Research, Girona, Spain. 27 University Jaume I, Castellón, Spain. 28 Faculty of Sci‑ence, Centre RECETOX, Masaryk University, Brno, Czech Republic. 29 Ecotox
Centre Eawag, Dübendorf, Switzerland. 30 Department of Chemistry, Universityof Bath, London, UK. 31 Department of Chemistry, Aristotle University of Thes‑
saloniki, Thessaloniki, Greece. 32 Vrije Universiteit Amsterdam, Amsterdam,
The Netherlands. 33 BRGM, Orléans, France. 34 Lulea Technical University, Lulea,
Sweden. 35 VÚVH, Water Research Institute, Bratislava, Slovakia. 36 Plentzia
Marine Station–Univ Basque Country (PiE-UPV/EHU), Plentzia, Basque Country,
Spain. 37 Marine Institute, Galway, Ireland. 38 INRAE, Ur Riverly, Lyon, France.
39
The Environmental Protection Agency Ireland, Dublin, Ireland. 40 SYKE,
Finnish Environment Institute, Helsinki, Finland. 41 IRSA-CNR, Water ResearchInstitute, Brugherio, Italy. 42 RIVM, Centre for Sustainability, Environmentand Health, Bilthoven, The Netherlands. 43 Department of Environmental Sci‑ence, Radboud University Nijmegen, Nijmegen, The Netherlands. 44 Fraun‑
hofer Institute for Molecular Biology and Applied Ecology IME-AE, Schmal‑lenberg, Germany. 45 University of Amsterdam, Amsterdam, The Netherlands.
46
LCSB, University of Luxembourg, Belvaux, Luxembourg. 47 LfU, Bavarian
Environment Agency, Augsburg, Germany. 48 RWS, Ministry of Infrastructure
and the Environment, Nijmegen, The Netherlands. 49 Department of Environ‑mental Science, Aarhus University, Aarhus, Denmark. 50 Middlesex University,
London, UK.
1

Received: 31 May 2020 Accepted: 6 July 2020

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