Key messages

• The project focuses on improving food safety by detecting hazardous chemicals, including unknown and emerging contaminants, in food products.
• Traditional testing methods only target known compounds, but this project uses high-resolution mass spectrometry to identify a broader range of potential food contaminants.
• The project explores how advanced screening methods can be incorporated into food monitoring and control plans to detect complex contaminant mixtures.

Overview

Traditional food safety monitoring mainly relies on targeted analytical methods that focus on specific, known chemicals. However, the growing variety and quantity of both known and unknown chemicals in the market necessitate more comprehensive detection strategies.  

Currently, the presence of hazardous chemicals in food is monitored using targeted methods that focus on a limited number of compounds. Although laboratories are continuously expanding the list of chemicals they monitor, this strategy is inadequate for addressing hundreds of thousands of known and unknown chemicals that continuously enter the market or are produced as by-products. Advances in analytical technology, such as high-resolution mass spectrometry, allow for the identification of potentially hazardous contaminant in food samples using screening methods like suspect screening. Suspect screening is an approach that screens for chemicals suspected to be present in a sample, even if they are not confirmed.  

This project aims to develop innovative tools for analysing food samples, adapt them to fit regulatory needs, and promote consistency in food monitoring practices. 

It will compare various analytical strategies and workflows—from sample preparation to data processing—to identify their strengths and overlaps in detecting traces of known, emerging, and unknown chemicals in food. Additionally, the project will conduct a proof-of-concept study to assess the relevance of such developed screening methods as part of monitoring and control plans. This will help identify original contaminant mixtures from real-world data and contribute to the early warning system for emerging chemical concerns, ultimately benefiting food policy makers.  

Achievements & Results

The interlaboratory exercise was designed through a collaborative process involving all project partners. An online survey and detailed questionnaire collected information on partners’ analytical capabilities, preferred food matrices, and in-house protocols for sample preparation and analysis. This input was used to finalise the experimental design during an online meeting held in February 2024, with further refinements based on feedback from the partners and discussions with work package leaders.

The finalised experimental design included the analysis of two food matrices—baby food and honey—fortified with 30 substances, comprising 10 known and 20 unknown compounds. Samples were prepared at three concentration levels (blank, low, and high) and distributed to partners for analysis using their preferred methods involving liquid or gas chromatography coupled with High-Resolution Mass Spectrometry ↗. A total of 54 samples per partner were provided for triplicate extraction and analysis.

In November 2024, all samples were sent to all project partners, officially launching the interlaboratory comparison.

Policy relevance

This project will evaluate laboratories' capabilities to perform analyses with new instruments and methods, harmonize results and approaches, and assess their suitability for regulatory applications.

Key messages

• The project will provide valuable EU-specific data on chemical exposures and risks faced by workers in e-waste and plastics waste streams.
• It will generate evidence to support policies aimed at worker protection, public health, chemical safety, and environmental sustainability.
• By fostering training and knowledge exchange, the project will strengthen collaboration and enhance the capabilities of EU laboratories and research centres.

Overview

In 2020, the European Commission adopted a new Circular Economy Action Plan ↗, acting as one of the main building blocks of the implementation of the European Green Deal ↗, Europe's agenda for sustainable growth. Taking the entire life cycle of products into account, this action plan targets how products are designed, consumed and dealt with in the waste stream. With an adoption, the EU aims to make its economy fit for a green future, strengthen competitiveness while protecting the environment and provide new rights to consumers. The waste management sector is expected to play an important role in this development.  

This project focuses on two key waste streams, electronic waste ↗ and plastics ↗ coming from both private households and the industry. Through collaborative discussions among relevant stakeholders, mainly companies, associations, and workers representatives within the waste management sector, this project will identify significant waste streams that are becoming more relevant due to the expected increase in recycling and therefore also to the labour force needed in this sector.  

• This cross-sectional study, which involves 18 partners, aims to:
• Provide data on waste management workers’ exposure to various substances, through both environmental and biological monitoring.
• Assess the effectiveness of existing European regulations in minimising the presence of harmful substance within the circular economy ↗, thereby reducing exposure for workers and the general population.
• Translate the findings from occupational studies into a framework that outlines implications for general population exposure.

Results of this study will carry valuable information across various regulatory frameworks like the multi-annual strategies on Occupational Safety and Health (OSH ↗) and the EU regulation evolving around the production and use of chemical substances, such as the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH ↗). Additionally, regulations related to waste management, water and soil protection as well as standards for food and consumer products, will also benefit from this study’s findings.

Achievements & Results

In the first year of the project, foundational steps were completed, including finalising the list of chemicals and exposure biomarkers, defining study protocols and detailed standard operating procedures, and identifying participating companies. The protocols made in the scope of the human biomonitoring project HBM4EU ↗ were adapted to include new biomarkers.  

In the second year, study protocols were submitted to ethical committees, a data management plan was developed, and online training was conducted to support partners in implementing procedures. Biomonitoring and environmental monitoring campaigns began, with institutions from across Europe participating.  

By the third year, sampling campaigns began in many EU member countries after receiving ethical approvals. Key achievements include defining biomarkers for each waste stream, adapting protocols to include new biomarkers and matrices, and creating training materials for field teams. Many partners have started sampling activities, advancing the assessment of chemical exposures in waste management sectors.

Policy relevance

The project will provide exposure data to support regulatory processes under OSH ↗ standards as well as under the REACH ↗, addressing the production and use of chemical substances, and their potential impacts on both human health and the environment.

Key messages

• The project houses different case studies on environmental burden of disease (EBD) of chemicals.
• FAIRification of data applied in the case studies is a must.
• Identification of datagaps on exposure, exposure-response and health outcomes is included in the lessons learnt from the case studies.

Overview

To protect people’s health, we need to understand how chemicals in the environment affect us. This project is improving access to essential data needed to measure the health impacts of harmful chemicals identified as priorities within PARC.

Right now, key information is often missing – such as how much people are exposed to chemicals (internally or externally), how this exposure varies by location, job, income, or age, and what health effects might follow. This lack of data makes it difficult to estimate how much disease or harm is caused by chemicals (EBD) and to carry out health impact assessments (HIA) ↗.

This project is:

• identifying data gaps and increasing the availability of high-quality information on exposure and health outcomes;
• focusing on specific groups like vulnerable populations and workers, and different exposure scenarios;
• supporting regulators in assessing risks, setting priorities, providing indicators and developing fairer chemical policies.

It contributes directly to the EU’s Zero Pollution Action Plan ↗, especially the goals of reducing health inequalities and tracking progress towards cleaner, safer environments. Pollution doesn’t affect everyone equally – so better data helps ensure that policies protect those most at risk.

Working alongside three other related projects (case studies, methodological progress and indicators), this effort feeds into the development of stronger methods and indicators to guide future health and environmental decisions.

Achievements & Results

The following assessments have already been completed:

• Impact of pyrethroid-insecticide exposure and ADHD in Europe based on HBM data (VITO);
• Cardiovascular diseases attributable to lead exposure in European adults (DTU);
• Burden of lead and methylmercury exposure on IQ loss in children in Europe – single-substance and mixture approach (ANSES);
• Impact of municipal solid waste incineration emissions on cancer-related mortality (FMUL);
• Burden of disease study on arsenic exposure and lung, bladder, and skin cancer (Sciensano);
• Influence of waste co-incineration in a cement plant on cancer burden (OI and NIJZ).

Ongoing assessments and activities:

• Possible impact of glyphosate-based herbicides and diabetes in EU countries (IRAS);
• Incorporating a time-to-event model to improve the prediction of age of onset or death (RIVM);
• Impact of exposure to PFAS and infectious diseases (VITO);
• Exposure to cadmium and chronic kidney disease (Sciensano);
• Exposure to a mixture of cadmium and lead and nephrotoxicity (Sciensano);
• Probability modeling in burden of disease (UBA).

Policy relevance

Through environmental burden of disease assessment a prioritisation can be initiated on the potential impact of chemicals in the EU. Health impact assessment provide evaluations of scenarios or policies. The different case studies provide a more robust estimate on the burden of disease caused by different chemical stressors. Indicators can be developed on exposure, risk and burden to inform policymakers.

Key messages

• Closing critical data gaps on BPA alternatives for hazard assessment across five key toxicological endpoints.
• Providing regulatory agencies with data to support safer substitutions and regulatory decisions.
• Utilising advanced methods and multi-institution collaboration to ensure reliable results.

Overview

Bisphenol A (BPA) ↗ is a chemical which is mainly used in the production of various plastics for the manufacturing of consumer goods. It is a widely used and studied chemical that has been proven to be harmful to human health. Thus, over the course of the decade, there has been an increase of restrictions on the use of BPA, which in turn led to an introduction of several chemical substitutes ↗.  

Since their introduction, chemical substitutes to BPA have already been found in humans and the environment, raising concerns about their safety of use. For most BPA alternatives, information on potential effects on human and environmental health is either missing or too limited, restricting a sound hazard assessment or characterisation.  

With further restrictions on BPA in the coming years, the use of BPA alternatives is projected to significantly increase, giving the scientific assessment of these substances great significance.

The project will fill knowledge gaps on the effects of eight prioritised BPA substitutions on human health following five toxicological endpoints:

1. Endocrine disruptors, also referred to as hormonally active agents;
2. Developmental neurotoxicity, meaning toxic substances influencing the development of nervous systems;
3. Immunotoxicity, regarding toxic agents effecting the immune system;
4. Non-genotoxic carcinogenicity, as tumour inducing substances; and
5. Metabolism, meaning chemical reactions in the human body.

Another contribution of this project will be the identification of molecular biomarkers in order to develop a method to rapidly predict potential effects of BPA alternatives on human health. Identifying these biomarkers will help determine the mechanism(s) through which BPA alternatives act, revealing their adverse health effects. 

Achievements & Results

A collaborative workshop with key stakeholders, including the European Chemicals Agency (ECHA ↗) and the European Food Safety Authority (EFSA ↗), successfully prioritized eight alternatives to bisphenol A (BPA) for detailed toxicological assessment. A list of the prioritised alternatives and the methods used for prioritisation are documented in an additional deliverable on the hazard assessment activities. Early toxicological evaluations of these BPA alternatives suggest that some may have potential adverse effects, highlighting the importance of thorough assessments to prevent regrettable substitutions. The project has also fostered stronger partnerships among the 13 project participating institutions across Europe, promoting interdisciplinary collaboration and addressing critical data gaps in chemical safety research.

Policy relevance

Filling data gaps for the hazard assessment for BPA alternatives, that will be useful in avoiding adverse effects of substitutions.

Overview

Developing a long-term, sustainable and inclusive human biomonitoring (HBM) ↗ framework for assessing chemical exposure across Europe is the main objective of this project. It is building upon previous initiatives, including the HBM4EU aligned studies ↗ and the PARC aligned studies, while integrating insights from global experts in Europe, the USA, Canada, Japan, etc.

Current HBM efforts, such as those under PARC, are providing valuable data on chemical exposure ↗, but a long-term, standardized system ensuring continuous and harmonised human biomonitoring is missing. The main challenges include streamlining HBM efforts between EU countries to develop a cost-efficient EU wide Human biomonitoring program that delivers harmonised data collected across EU countries and ensures truly representative results for policymakers and address public concerns.

By 2028, a concept for such an EU wide HBM program will be prepared. This system ensures to generate EU-wide comparable HBM data, optimising resources by improving study design and reducing costs, and supporting policy decisions with reliable data on chemical exposure. It is also enhancing public health protection by addressing risks from environmental, dietary, and consumer product exposure.

The framework is aligning with European regulatory processes governing chemical use, environmental safety, and human health. It is serving as the foundation for the future EU-wide HBM campaigns, adapting to evolving regulatory needs and scientific advancements to ensure a safer and healthier environment for European citizens. 

Achievements & Results

Part of the project is focused on building a network of international HBM experts (beyond Europe) and facilitating knowledge exchange. In the margin of the annual meeting of the International Society of Exposure Science (ISES ↗) partners of the PARC sustainable HBM project have organized a get together with international HBM experts from the US, Canada, Japan, Taiwan, Korea. In previous meetings the topics of sustainability and communication were addressed.

The project delivered feedback to the legal proposal ↗ for a common data platform on chemicals, establishing a monitoring and outlook framework for chemicals regarding sustainability of HBM activities in Europe. 

Key messages

• Assessing chemical exposure at early stage of life is still a challenge.
• Today, new tools are available that enhance chemical exposure assessment.
• Efforts are ongoing to refine and clarify the applicability and effectiveness of these approaches.
• Their value in chemical prioritisation and contribution to early warning systems has been well established. 

Overview

To accurately reflect the complex reality of human exposure to chemicals, new conceptual frameworks and innovative methodological approaches are essential, encompassing every step from sample collection to the generation and analysis of exposure data. While promising new approaches are available, they require further development and rigorous performance evaluation before they can be widely implemented in large-scale human cohort studies.

Agencies such as the European Food Safety Authority (EFSA ↗) and the European Chemicals Agency (ECHA ↗) have highlighted the critical importance of early-life human exposure, particularly in the context of risk assessment and its implications for long-term health, as described by the Developmental Origins of Health and Disease (DOHaD ↗) concept. 

New sampling techniques, such as silicone wristbands and dried blood spots, offer non-invasive solutions for collecting samples from vulnerable populations like infants and children, where minimising invasiveness and sample size is paramount.

In parallel, suspect and non-targeted screening (SS/NTS ↗) approaches, leveraging high-resolution mass spectrometry and effect-directed analysis (EDA ↗), are gaining traction in analytical laboratories. These methods are designed to detect a broad spectrum of chemicals without prior knowledge of specific substances, enabling the identification of unexpected or previously unknown exposures.

This project aims to develop and validate a proof-of-concept to evaluate the performance and potential of these innovative methods as complementary tools to traditional, targeted approaches. The focus is on analysing human samples collected from mother-child pairs. These screening methods are designed to simultaneously detect diverse substances from multiple chemical classes, including both persistent and non-persistent organic pollutants of emerging concern. 

Achievements & Results

In Year 1, the project achieved key milestones, including finalising the global roadmap, developing a detailed work plan across three experimental pillars, identifying initial sample sets, arranging material transfer agreements and sample shipments, and sharing existing standard operating procedures for analytical methods.

By Year 2, partner roles were consolidated, and initial sample analyses (pillar 1) and interlaboratory assays for screening techniques (pillar 2) began, with both on track. Additionally, a working group on innovative sampling methods was established, conducting a literature review to identify existing knowledge and gaps. 

In Year 3, data analysis for the first round of sample characterisation and interlab assay results is underway, alongside progress in method harmonisation and experimental testing of clean-up procedures to refine standard operating procedures for sampling tools like silicone wristbands. 

Policy relevance

• Elaboration of templates for harmonised reporting of SS/NTS data and interlab assay.
• Contribution to the elaboration of a common QA/QC chemical mixture for harmonised method performance assessment to be possibly further handled by JRC as reference.
• Contribution to documenting real-life chemical exposure in perinatal period as a basis for further prioritisation of action. 

Key messages

• Human biomonitoring (HBM) data are being used to calculate the health impact of chemical exposure.
• Risk indicators as percentage of exceedance, extent of exceedance gives information if and how much human biomonitoring guidance values are breached or not.
• Indicators on burden of disease as attributable cases or disability adjusted life years (DALYs) provide information on the health impact.
• Indicators inform policymakers and can help to prioritise action with the primary goal to lower the impact of chemicals on our health.

Overview

Markers that reflect the health impact of chemical exposure are essential tools for national and European policy makers, helping to shape and support monitoring frameworks such as the Chemical Strategy for Sustainability ↗, the Zero Pollution Action Plan ↗, and the 8th Environment Action Programme ↗.

The choice of a health impact indicator depends on several factors, including the specific policy questions it aims to address, the availability and quality of data, the uncertainties associated with each indicator, and the resources and expertise required.

Indicators used to assess the harmful effects of chemicals include the number of attributable cases, the measurement of DALY or Quality-Adjusted Life Years, and the calculation of external costs. DALY represent the total years of healthy life lost due to illness, disability, or premature death. In situations where data are insufficient for a full health impact analysis, the exceedance of health-based guidance values already serves as a risk indicator. This approach estimates the portion of the population exposed to chemical levels above these guidance values, signalling a potential health risk.

This project is one of four interconnected initiatives focussed on assessing the health impacts of chemical exposure and works closely with related projects on data collection, methodological improvements, and case studies. Currently the focus in on the case studies from which indicators on health risk or impact can be developed to inform policymakers.

Achievements & Results

In this project,  an  inventory  of  existing  types  of  exposure, risk  and  health  impact indicators was compiled, including their application in regulatory and policy frameworks, based on expertise available among partners, literature search, communication materials of (inter)national organisations, and stakeholder input (JRC ↗ and EEA ↗ for indicators related to the Chemical Strategy for Sustainability ↗ and Farm to Fork Strategy ↗). Together with the case study prioritisation, this forms the basis for a proposal for indicator development. 

The first case study focused on the association between pyrethroid exposure and ADHD. The results are available here ↗.

Additional case studies scheduled for completion in 2025 include:

• Exposure to a mixture of lead and methylmercury and IQ loss.
• Exposure to lead and cardiovascular disease through hypertension.
• Exposure to arsenic and carcinogenic effects.
• Environmental burden of municipal solid waste incineration emissions on cancer-related mortality.
• Influence of waste co-incineration in a cement plant on cancer burden and risk assessment for selected chemicals based on HBM data.

Policy relevance

• Indicators on exposure to chemicals.
• Indicators on risk assessment (exposure vs hazard).
• Indicators on possible health impact (attributable number of cases, DALYs).
• These indicators inform policymakers and help with preparing, evaluating policy.

Key messages

• Nurses and other workers in hospitals may become exposed to various hazardous medicines unless proper precautions are taken.
• New measured data on exposure to hazardous medicines are collected together with detailed information on practises applied at hospitals to promote safe handling practises.
• The study supports the implementation of EU legislation on carcinogenic, mutagenic and reproductive toxic chemicals at work and its recent updates concerning the hazardous medicines. 

Overview

This cross-sectoral study focuses on hazardous medicinal products, such as cytotoxic drugs ↗, inhalation anaesthetics, and disinfectants. Cytotoxic drugs, which are medications commonly used in chemotherapy to treat cancer, work by destroying or preventing the growth of cancer cells. However, these drugs can also pose risks to human health because they often have harmful properties, including the ability to cause cancer (carcinogenic), create genetic mutations (mutagenic), or negatively affect reproduction (reproductive toxicity). Similarly, common inhalation anaesthetics have been suggested or are known to exert reproductive toxic properties. The aim of the study is to introduce human biomonitoring for assessing both exposure and early health effects in healthcare settings. It will take place in 20-24 hospitals across 10-12 EU member states, with the following objectives:

• Identify key exposures and relevant exposure scenarios in hospitals
• Explore how human biomonitoring can improve chemical risk assessments for priority chemicals in healthcare environments
• Examine the contributions of various exposure sources—such as drug spillages, patient excreta, and drug packaging—to assess aggregated exposure to these medicines in hospital settings
• Develop human biomonitoring-based approaches to better assess and manage chemical exposures in hospital settings

The project aligns with recent guidelines for hazardous drugs, including cytotoxic drugs, ensuring compliance with occupational health and safety protections outlined by the EU Occupational Safety and Health Directive ↗ and the Carcinogens, Mutagens and Reprotoxic substances Directive ↗. These were recently amended to include also hazardous medicinal products and reproductive toxic compounds. In this way, the study addresses key regulatory developments and contributes to the improvement of occupational health and safety standards in the healthcare sector.

Achievements & Results

A consortium of institutes from 11 countries has been established, with partners confirming their participation to recruit hospitals and study participants. Together, the consortium identified priority chemicals for the study and selected specific biomarkers to measure exposure and effects. A generic study design has been developed, alongside detailed protocols for hospital recruitment, participant involvement, information sharing, questionnaires, and the collection, storage, and shipment of biological samples.

The digitalisation of the workers' questionnaire has been completed, and candidate laboratories for biomarker analysis have been identified. Quality assurance and control measures for biomarker and occupational hygiene sample analyses have been developed, with sampling already underway in some countries.

The study’s focus on hazardous medicinal products was narrowed to cytotoxic drugs, as there was insufficient support to include antibiotics or other medicinal products.

Work is ongoing to prepare information materials for hospitals and workers. Informal discussions with the European Commission's Directorate-General for Employment (DgEMPL ↗) and the European Agency for Safety and Health at Work (EU OSHA ↗) have helped shape the project design. A protocol paper detailing the study methodology is currently being drafted.  

Policy relevance

• The project supports the implementation of the recent updates to EU CMRD, which now includes hazardous medicinal products. 

Key messages

• Developing three sets of health-based Human Biomonitoring Guidance Values helps to interpret biomonitoring results for the general population and workers.
• Human Biomonitoring Guidance Values are created for substances with a clear threshold where health effects occur. For carcinogenic substances that don’t have a safe threshold, special values called Exposure Equivalents for Cancer Risk are developed in certain cases.
• These guidance values will make it easier to assess chemical exposures and protect the health of different groups. 

Overview

This project aims to develop guidance values for human biomonitoring of priority chemical substances, using measurable biomarkers of exposure as a foundation for accurately interpreting potential health impacts. Biomarkers of exposure are substances in the body, such as chemicals or their breakdown products, that indicate whether and how much someone has been exposed to a chemical. The human biomonitoring guidance values, developed through collaborative consensus within the Partnership for the Assessment of Risks from Chemicals (PARC) project, will standardise the assessment of human biomonitoring results and support European chemicals policies.  

To enable a health-related interpretation of human biomonitoring results, human biomonitoring guidance values must be derived from epidemiological or toxicological data and correspond directly to measurable human exposure biomarkers. Epidemiological data refers to data or evidence relating to the occurrence, distribution, clinical characteristics, and control of disease within a group of people while toxicological data are used to evaluate the potential harm or hazard of a chemical. The main aim of this project is to create as many guidance values as possible for priority chemicals identified by PARC and measured in the Aligned Studies.  

Through the consensual approach, broad acceptance and promotion of the harmonised assessment of human biomonitoring results should be ensured. The guidance values for both the general population and worker groups are derived according to the agreed human biomonitoring guidance value methodology. However, ongoing refinement of this strategy will be incorporated as new data emerge. In certain cases, molecular modelling—a computer-based method for predicting how chemicals behave in the body—may be required, and corresponding results will be made available within PARC. Each human biomonitoring guidance value will include a confidence level, which indicates the degree of certainty about the value’s accuracy. 

Achievements & Results

The first values and associated substance dossiers are currently being finalised. The substances included in this initial release are:

• DHHB (diethylamino hydroxybenzoyl hexyl benzoate, Uvinul® A Plus
• (Gamma/Lambda) Cyhalothrin
• Benzophenone-3
• Diisononyl Phthalate (DiNP)
• Diethylhexyl Terephthalate (DEHTP)
• Aluminium
• Nickel
• Chromium VI
• Mercury
• Acetamiprid
• Imidacloprid 

Policy relevance

The evaluation of European human biomonitoring results with the help of harmonised guidance values makes it possible to check legal chemical regulation on their sufficiency or needs of improvement. 

Key messages

• Identifying toxicological effects of selected enniatins and Alternaria toxins.
• Providing urgently needed in vitro data for an appropriate risk assessment.
• Aim to set health-based guidance values for food (and feed).

Overview

Mycotoxins ↗ are secondary metabolites produced by fungi that can contaminate food (e.g. cereal products, fruits, and beverages) and animal feed. These toxins can have harmful effects, ranging from neurotoxicity (damage to the nervous system) to carcinogenesis (the development of cancer).

Due to the widespread human exposure to these toxins – an issue likely to worsen in Europe with climate change and the lack of mandatory reporting on their hazards – the Partnership on the Assessment of Risks from Chemicals (PARC) has identified the need for reliable toxicity data as a priority. This effort is supported by regulatory authorities, including the European Food Safety Authority (EFSA ↗)’s CONTAM Panel ↗, which assesses contaminants in the food chain.

This project focuses on two emerging groups of fungal toxins, enniatins and Alternaria toxins, which require urgent regulatory attention due to limited data on their potential health risks.

The main goal is to address gaps in knowledge about their harmful effects on human health by studying the following areas:

• Genotoxicity and mutagenicity: The potential of these toxins to damage genetic material which may lead to mutations.
• Endocrine effects: How these toxins may interfere with hormonal systems.
• Immunotoxicity: The effects of these toxins on the immune system’s ability to function properly.
• Metabolism: How the body processes these toxins, including pathways that may activate or deactivate their harmful properties and how they move through the body (toxicokinetics).

This research aims to provide critical data to support regulatory decisions and protect public health.

Key messages

• From 2022 – 2029, 67 institutions are collaborating under the EU Partnership for Assessment of Risks from Chemicals (PARC) initiative to enhance the utility of innovative analytical methods and tools for monitoring and surveys, supporting next-generation chemical risk assessment.  
• A network of harmonised laboratories operating standardised innovative methods for chemical exposure characterisation should be established for use as a tool within a European early warning system for chemical risks. 

Overview

This project evaluates how effectively European regulations minimise the risks posed by chemical use, protecting public health and the environment. By monitoring chemicals in people's bodies across different European regions using a harmonised approach and quality-assured analytical methods, this project will assess the impact of policies like the European Green Deal ↗ and the Chemicals Strategy for Sustainability ↗. It aims to understand how chemical exposure varies based on local environment, lifestyle, and diet. In addition, this project tracks emerging chemical risks and evaluates their health impacts, guiding safer chemical practices and preventing harmful substitutions. These efforts help ensure ongoing safety and build public trust in chemical management. The findings will be relevant to policy makers and regulatory frameworks that restrict chemical production, use, and environmental release, as well as those focused on environmental and human health protection.

Demonstrating the effectiveness of existing policies is essential for maintaining public trust and securing the ongoing collaboration of industry and stakeholders. Human biomonitoring is a tool of health-related environmental monitoring with which populations are examined for their exposure to pollutants from the environment.

When carried out across Europe, this tool provides consistent data on the internal exposure of the European population to priority substances within the Partnership for the assessment of Risks from Chemicals (PARC), in different European regions. The results from European partnerships like the European Human Biomonitoring Initiative (HBM4EU ↗) and PARC, offer a baseline and when repeated show trends over time. These data help track the success of initiatives like the European Green Deal's Zero Pollution Action Plan ↗ and the Chemicals Strategy for Sustainability.

This project will also identify exposure to new and potentially concerning chemicals, including substitutes for banned substances. Detecting these chemicals in the population can serve as an early warning system of hidden risk. By measuring biological markers that show how chemicals affect the body and linking them to health data, this study will provide insight into how these chemicals, including substitutes, impact health. This will also support efforts to group chemicals and avoid harmful substitutions.  

Achievements & Results

Although the primary project results are expected in 2027/2028, progress has been made in the preparatory phase. Participating countries contributing with human biomonitoring data have been identified, and supporting materials, including questionnaires, have been developed. The selected target groups include children (6-11 years), teenagers (12-17 years), and adults (18-39 years) and a finalized list of biomarkers includes substances like bisphenols, phthalates, PFAS, pesticides, metals, arsenic, and cotinine. Find out more about this here. 

A workshop held in Brussels on on 10 and 11 May 2023 brought together experts to align methodologies and protocols for PARC-aligned human biomonitoring studies. The workshop aimed to ensure a harmonised, consistent approach across participating countries, allowing for reliable and comparable data collection.

Initial studies have begun recruiting participants and collecting biological samples, marking the start of data generation for the project. This phase is crucial to generate high-quality data that will help assess chemical risks and policy effectiveness.

Policy relevance

Only a few countries have integrated exploratory analysis into regulatory frameworks for human, food, or environmental monitoring to support chemical risk assessment. This project identified key scientific barriers that must be addressed to incorporate advanced techniques like non-targeted analysis and effect-directed analysis into monitoring programs and early warning systems. These findings have been communicated to regulatory bodies and policymakers, providing valuable insights to guide priority-setting and assess the feasibility of adopting these innovative approaches in policy frameworks. 

Key messages

• The study identifies occupational exposure pathways and their health impacts, providing a foundation for evidence-based regulations to protect workers and reduce occupational health risks.
• Sentinel surveillance delivers early warnings on emerging health threats, enabling timely preventive actions and enhancing EU health resilience.
• The findings support targeted strategies to prevent work-related diseases, reducing the economic burden on healthcare systems and industries.
• Research fosters EU-wide collaboration and harmonisation, enhancing regulatory frameworks for occupational health and safety across Member States.
• Insights promote sustainable practices, aligning with EU Green Deal goals by enabling the substitution of hazardous substances with safer alternatives. 

Overview

A Sentinel Surveillance System in occupational settings is a strategic and cost-effective tool for monitoring health issues linked to environmental and occupational exposures, using the expertise of trained occupational health and safety professionals. This system involves selecting specific locations to gather comprehensive data on occupational and environmental health conditions alongside exposure data for substances of high concern. Sentinel surveillance generates vital data for advancing exposome research, improving innovative approaches in exposure studies, and offering cost-efficient methods for biomonitoring exposure data. 

Establishing national sentinel surveillance platforms enhances data collection in workplace settings, enabling continuous monitoring of exposure levels and related health outcomes. Additionally, the system serves as an early warning system for identifying and addressing emerging threats in workplaces.

This project aims to establish a European sentinel surveillance system to support human biomonitoring surveys in the general adult population, using occupational physicians and nurses. Sentinel networks, made up of motivated physicians, provide and efficient way to collect data and samples, a method that has proven successful in occupational health studies. The primary objective of this project is to assess the feasibility of using a sentinel system to enhance human biomonitoring surveys, covering a broad range of chemical exposures, including PFAS ↗ (also known as "forever chemicals"), pesticides ↗, bisphenols ↗, metals, and mercury ↗.

By involving occupational physicians and nurses, the project aims to improve recruitment for the Partnership for the Assessment of Risks from Chemicals (PARC) general population human biomonitoring survey, providing critical data on the environmental and occupational exposure for a representative sample of European working adults. This initiative supports regulatory frameworks related to the general population human biomonitoring survey and aligns with the EU’s Health & Safety at Work – Strategic Framework (2021-2027) ↗, which focuses on guidelines and standards for protecting workers’ health and safety.  

In addition, this project contributes to the EU's objectives of zero pollution ↗, one-substance-one-assessment ↗ approach, and exposome initiatives ↗ by generating aggregated exposure data from various sources. Ultimately, the project functions as a strategic tool to address current and emerging health risks, while promoting a safer working environment in line with EU regulations and standards.

From an international perspective, establishing and implementing a sentinel surveillance approach across EU countries, combined with training occupational health and safety professionals in assessing occupational and environmental exposures, is seen as a promising strategy. This approach has the potential to generate more reliable data and enable meaningful comparisons of large-scale exposure information across nations. 

Achievements & Results

In Belgium, a significant milestone has been achieved with the development and launch of the Human Sentinel Surveillance Platform (HSSP ↗), a web-based sentinel surveillance tool. The platform is currently undergoing testing to evaluate its feasibility for national-level surveillance of occupational chemical exposures. 

Policy relevance

• This project aims to explore, design, and test the feasibility of, and implement a European sentinel surveillance system to support human biomonitoring and assess the exposure of a representative sample of European working population exposed to substances of high concern. This will be achieved through the involvement of motivated and specifically trained occupational physicians and nurses, familiarised with the sentinel approach and human biomonitoring.
• The project hold significant potential to support regulatory processes under the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) and the Occupational Safety and Health (OSH) field. REACH regulations play a critical role in assessing chemical risks and proposing risk management measures, ensuring the protection of both the environment and the health of workers exposed to these substances in the workplace.  
• Meanwhile, the concept of a Sentinel Surveillance System has emerged as a dynamic tool for advancing occupational health within OSH regulations. By systematically monitoring workplace environments and the health of workers exposed to substances of high concerns, this system provides a robust framework for the early detection of hazards, proactive interventions, and data-driven decision-making. 

Key messages

• Novel approaches for assessing chemical exposure bring significant progress in detecting chemical burden, but challenges remain due to the complexity of chemical behaviour and the limitations of covering the entire chemical space.
• Some chemicals metabolise rapidly or accumulate in tissues not routinely investigated in classical human biomonitoring, risking underestimation of true exposure unless complementary matrices are investigated.
• Ongoing research aims to evaluate the applicability and added value of these complementary analytical strategies.
• The potential of these approaches for chemical prioritisation and their contribution to early warning systems is under active investigation.

Overview

This project aims to enhance the detection and understanding of human exposure to chemical contaminants by applying and evaluating advanced, complementary methodologies. Building on previous studies focused on perinatal and occupational exposure, it explores additional innovative strategies to strengthen existing suspect and non-targeted screening. It investigates complementary separation techniques, such as hydrophilic interaction liquid chromatography, and assesses the potential of ion mobility mass spectrometry to add an extra dimension of separation.

To further broaden the range of detectable substances, the project also evaluates alternative sample preparation methods, including, dilute & shoot and the use of supramolecular solvents as an alternative to conventional extraction technique. These developments are applied to human biomonitoring samples to demonstrate their practical applicability, while simultaneously identifying biomarkers that may support chemical prioritisation efforts and contribute to early warning systems.

In parallel, the project investigates the use of alternative, non-invasive biological matrices such as hair, to capture additional biomarkers if exposure that may be overlooked when relying solely on traditional matrices like urine and blood. Current regulatory frameworks struggle to keep pace with the expanding chemical landscape and emerging contaminants.

This initiative supports the development of more responsive and adaptive approaches by improving the practical application of high-resolution mass spectrometry-based methods and expanding the scope of detectable substances.

Additionally, the project integrates insights from cross-cutting efforts in quality control and data processing, applying them to new sample sets and reinforcing the connection to aligned studies. Ultimately, this work supports the early identification of chemical hazards and contributes to the evolution of safer, more proactive regulatory practices.

Achievements & Results

• The project demonstrated the applicability of hydrophilic interaction liquid chromatography for biomonitoring polar biomarkers of exposure.
• The project explores the usefulness of hair as an alternative matrix to complement innovative approaches for assessing chemical exposure.
• The project will evaluate the advantages, limitations, and applicability of various sample preparation methods, providing evidence to identify which approach best serves as a general method for capturing the broadest chemical space.
• Several cohorts of human biomonitoring samples have been selected and will be analysed using these innovative approaches to: document real-life chemical co-exposures and support chemical prioritisation; provide proof-of-concept for the applied methodologies; address specific research questions related to the characteristics of selected cohorts; and validate outputs of other PARC projects, in particular "Harmonising quality of chemical and bio-effect directed suspect and non-target screening methods across fields" and "Establishment of advanced data processing methodologies and bioinformatic tools for a non-targeted screening repository".

Policy relevance

• Broader compound coverage and improved capacity to monitor exposure trends will strengthen understanding of the chemical exposome and support the development of more effective prevention and risk management measures.
• Contribution to the development of templates for harmonised reporting of non-targeted and suspect screening data.
• Contribution to the preparation of a common QA/QC chemical mixture for harmonised method performance assessment.
• Contribution to documenting real-life chemical exposures in specific human biomonitoring subgroups, providing a basis for further chemical prioritisation.

Key messages

• MnHexP exposure evaluation on European level;
• Potential source UV-filter DHHB.

Overview

This project addresses an urgent need identified by the European Environment Agency (EEA) ↗ and the European Chemicals Agency (ECHA) ↗ in February 2024, which triggered the activation of PARC’s Rapid Response Mechanism. The concern arose from recent human biomonitoring (HBM) data showing elevated levels of mono-n-hexyl phthalate (MnHexP) exposure in Germany and Denmark, highlighting a pressing demand for updated information on chemical exposures at both EU and national levels.

Although various parent compounds, such as mixed-chain phthalates, may contribute to this exposure, current evidence points to contamination of the UV filter diethylamino hydroxybenzoyl hexyl benzoate ↗ (DHHB) with di-n-hexyl phthalate ↗ (DnHexP) as the most likely source.

Using a tiered approach, the project will begin by collecting and assessing existing data on human exposure and potential sources. These findings may inform the Classification, Labelling and Packaging ↗ (CLP) dossier on C4–C6 phthalates currently being developed by France and potentially support a restriction dossier under REACH ↗ relating to PVC and its additives. The project will also evaluate samples from indoor environments to explore exposure pathways. In its final phase it aims to gather data from new human biomonitoring, environmental, and product measurements as part of PARC Aligned Studies to better understand the extent of MnHexP exposure across Europe.

The project contributes directly to PARC's objectives of supporting regulatory action, ensuring the public availability of data, and enhancing citizen awareness. It also addresses a previously under-explored phthalate metabolite in PARC's research agenda.

Key messages

Health impact assessment is a tool that provides policymakers with insights into the health burden that is attributable to chemical exposures and helps them to prioritise preventive measures. Improved methodologies and data are needed to reduce uncertainties of the estimated health impacts.

Overview

Environmental Burden of Disease (EBD) and Health Impact Assessment (HIA) are tools to provide policymakers with insights into the impact of (changes in) environmental exposures on population health. This project aims to improve health impact assessments for chemical exposures by making methods more reliable and expanding the types of data used to reduce uncertainties about health impacts and to strengthen the scientific basis for policymaking.

Currently, many health impact assessments are limited by missing or inconsistent data on exposure levels, health effects, exposure-response functions, and susceptible populations. By improving methodologies and integrating a wider range of data – including demographic, epidemiological and toxicological information – the project is making EBD and HIA calculations more accurate and useful.

This will help policymakers to carry out more informed evaluations, set priorities and plan actions to reduce health impacts from harmful chemicals. The work directly supports the EU Green Deal’s zero pollution ambition ↗, particularly the Chemical Strategy for Sustainability ↗, which aims to reduce pollution and its effects on the health and the environment.

The project is part of a broader group of four interlinked initiatives working on health impact assessment. Its results will feed into related efforts, including real-world case studies and the creation of indicators to measure chemical risks and health effects more effectively. By reducing uncertainty and improving data use, this project is supporting safer chemical policies and helping protect public health across Europe.

Policy relevance

This will help policymakers to carry out better evaluations, set priorities and plan actions to reduce health impacts from harmful chemicals. The work directly supports the EU Green Deal’s zero pollution ambition ↗, particularly the Chemical Strategy for Sustainability ↗, which aims to reduce pollution and its effects on the health and the environment.

Key messages

• Current biomonitoring methods are limited in assessing the full spectrum of chemical exposures, especially with emerging chemicals in occupational sectors.
• Innovative screening methods (SS/NTS) and new sampling tools (DBS, SWB) offer a promising alternative to traditional approaches, enabling more comprehensive exposure assessment.
• The project will demonstrate the proof of concept of these novel methods through real-life case studies, offering insights that will support policy, regulatory improvements, and enhanced risk management to better protect workers and guide future chemical exposure regulations in Europe.

Overview

The European Commission has adopted a new Circular Economy Action Plan ↗, promoting the reuse, recycling, and prolonged circulation of resources. While this shift is environmental beneficial, it may carry unintended consequences for workers. Those involved in the waste processing chain could face increased health risks due to heightened exposure to various substances during material reuse and recycling. While the move towards a circular economy is positive overall, we still need new and innovative methods to understand and manage these risks. Traditional analytical approaches focus only on known biomarkers of exposure, but they may fail to identify other potential risks associated with waste processing. In this context, suspect and non-targeted screening methods offer promising alternatives by enabling the detection of both known and emerging biomarkers of exposure and effect.

These advanced screening techniques, when paired with novel sampling methods such as dried blood spots (DBS) and silicone wristbands (SWB), represent a significant step forward in occupational biomonitoring. They offer non-invasive, practical options for monitoring complex exposures in real-world settings.

Despite their potential, these methods are not yet widely used in human exposure assessment ↗. Further development, validation, and harmonisation are required to ensure their reliability and applicability across Europe.

This project aims to develop and conduct a proof-of-concept study to evaluate the performance of these innovative approaches. It will also demonstrate how they can complement traditional methods by providing deeper insights into the nature and impact of occupational exposures among workers handling waste, ultimately supporting better prevention strategies and policy development.

Key messages

• Holistic PFAS biomonitoring in early development stage
• Monitoring of newborns and pregnant women
• PFAS exposure and pahtway gaps to be filled
• Potential refinement of regulatory thresholds

Overview

This project implements a longitudinal human biomonitoring (HBM) survey to investigate exposure to per- and polyfluoroalkyl substances (PFAS) ↗ in the most vulnerable population: pregnant women and their newborns. It follows participants across three key time points, collecting various biological samples – with a strong focus on breast milk – to detect both known and emerging PFAS.

Researchers will analyse the samples to map exposure levels, identify trends, and characterise maternal transfer pathways during pregnancy and breastfeeding. By doing so, the project fills critical data gaps in PFAS research, particularly around exposure during early development.

The project targets multiple European countries, including Luxembourg, Greece, Czechia, the Netherlands, Austria, Slovenia, Spain, Cyprus, Iceland and potentially Latvia. It generates essential exposure data tailored to local populations, informing national and EU-level risk assessments ↗. In turn, this helps regulators refine safety thresholds and update policies under REACH ↗, the EU POP Regulation ↗, and broader chemical safety legislation.

By actively contributing to the body of evidence on PFAS and its impact on human health, especially among sensitive groups, the project supports the EU Chemicals Strategy for Sustainability ↗. It not only strengthens scientific understanding but also enhances the regulatory framework needed to manage PFAS emissions and safeguard future generations across Europe.

Key messages

• The project develops a strategy to connect chemical exposures with health outcomes using effect biomarkers.
• It follows a two-step approach: integrating health data into human biomonitoring (HBM) surveys and assessing retrospective exposure through biobanked samples.
• It will deliver concrete tools for PARC surveys, including standardized procedures and materials for effect biomarker implementation.
• The results will strengthen the scientific basis for public health policies and chemical risk regulation in Europe.
• The project fosters a more integrated approach to biomonitoring by linking exposure data with health outcomes.

Overview

This project aims to assess adverse health impacts of chemical exposures by analysing biomarkers of effect ↗ in HBM studies. Biomarkers of effect are measurable indicators, such as specific proteins or metabolites in the body, that can show early signs of how exposure to a chemical can affect health. The project includes developing standardised methods to assess health outcomes, providing a clear and consistent approach to understanding links between chemical exposure and health effects. This study aims to create a roadmap outlining specific actions and tools for investigating these links within the Partnership for the Assessment of Risks from Chemicals (PARC).  

The project will be carried out in two phases. The first integrates standardised measures of effect biomarkers and health indicators, as well as health-related questionnaires, into existing human biomonitoring surveys. The second phase will assess past exposures to certain prioritised chemicals by analysing stored samples and examining links to current health outcomes. A case study will apply this method to a priority substance identified by the PARC project, using historical data to assess long-term effects.  

This project establishes a core strategy for linking past exposures to current health effects and creates a baseline assessment that will guide future surveys combining biomonitoring and health examinations.

The project will deliver tools and information for measuring exposure and health-effect biomarkers to complement classical toxicological, regulatory risk assessment. These findings will inform Governing Board members, European Commission, agencies and national bodies, policy makers and regulators across Europe. 

Overview

This project investigates how levels of internal exposure to environmental pollutants have changed over time across Europe. It builds on data collected from children, teenagers, and adults through previous and ongoing human biomonitoring (HBM) studies under HBM4EU ↗ and PARC. The main goal is to assess exposure trends and evaluate how effective past policies and regulations have been in reducing the public’s contact with harmful substances.

To achieve this, the project brings together partners who already manage studies with repeated measurement cycles or long-term data collections. Each partner will harmonise their data using a shared structure, validate it with a dedicated tool, and then apply common statistical methods using a jointly developed script. When possible, pooled analyses will be carried out on studies with overlapping substances and timeframes to strengthen the results.

The pollutants of interest include phthalates ↗, PFAS ↗, bisphenols ↗, pesticides ↗, heavy metals ↗, flame retardants ↗, UV filters ↗, PCBs ↗, acrylamide ↗, and others. If data gaps exist, stored biobank samples may be used to fill them through new chemical analyses.

The findings will help national and EU authorities ↗ assess the real-world impact of existing chemical safety measures. By showing whether exposure levels are rising, falling or stable, the results will guide future policies, help enforce existing rules, and support public health interventions. Ultimately, the project aims to protect citizens from hazardous substances by providing solid evidence to inform better decision-making.

Policy relevance

• This project will provide critical data on patterns of human exposure to pollutants, supporting the refinement of key EU and national regulatory frameworks such as REACH, the Chemicals Strategy for Sustainability ↗, and the Cosmetic Regulation.

Key messages

• By targeting children aged 6–11 across several European countries, the project provides crucial insights into PFAS exposure during a sensitive developmental stage for which data is lacking.
• The use of aligned protocols and tools from the PARC Aligned Studies ensures data comparability and reliability across participating countries.
• The use of innovative techniques, such as non-target screening, will enable the identification of emerging PFAS compounds that are not detected by traditional targeted studies. This approach allows for a more comprehensive assessment of PFAS exposure and helps to identify previously unmonitored or unknown substances.

Overview

Although PFAS are widely used and persistent in the environment and human body, existing biomonitoring data for children are very limited. This project addresses a regulatory gap by generating harmonised, EU-wide data on PFAS exposure in children, a vulnerable and underrepresented group in human biomonitoring. This project extends its scope to children aged 6–11, using aligned protocols and tools developed within the PARC Aligned Studies. Seven countries will participate, covering regions in Northern, Western and Southern Europe.

The project responds directly to the European Chemicals Strategy for Sustainability ↗ (CSS), which calls for the phase-out of PFAS use, and supports PARC priorities. By collecting and analysing serum samples, we aim to:

• characterise current PFAS exposure levels in children,
• establish internal exposure reference values,
• identify key determinants such as diet, socio-demographics, and indoor environment.

If health-based guidance values are available, comparisons will estimate the proportion of children at potential health risk. Links to environmental datasets and external studies may be explored to identify exposure sources.

This work will provide timely and policy-relevant data to inform national and EU regulatory measures on PFAS, including ongoing REACH restriction processes. Results will directly support evidence-based risk assessment and regulatory action, contributing to enhanced protection of children’s health and aligning with long-term EU policy goals.

Achievements & Results

At this point, a kick-off meeting of the project was held in Brussels on the 28 May 2025. Partners have started to collect blood samples from the selected children.

The first collected data will be available to share at the end of 2026.

Policy relevance

• By providing the first European HBM data allowing the description of PFAS exposure among young children, the project will set a baseline that will allow evaluation of new future regulation and further optimisations in time.
• The non-targeting experimental approach could bring some knowledge about new compounds actually not monitored by targeted screening and could help to enlarge the spectrum of further targeted PFAS compounds to be include under new regulation.
• The comparison of collected exposure data with a HBM-GV, if available, will supply a relevant information contributing to health risk assessment process.
• Collected individual data might be used to help deriving a new HBM guidance value specific for children by European agencies or national risk assessment agencies.
• This project will provide individual HBM data (accessible via IPChem to multiple authorities overseeing respective legislation such as EFSA, EEA, ECHA and EMA at EU level or national health authorities) that could contribute to develop new regulation and help democratising this process to further elaborate and evaluate new public policies in Europe.
• Results of the project can directly support the PFAS restriction under REACH by providing critical evidence to refine threshold values, prioritize high-risk uses for restriction.
• Data on children’s exposure could help identify priority PFAS substances for restriction under the POP regulation, ensuring alignment with its goals and effectiveness of this regulation.
• This project will also support the European CSS, which emphasizes the importance of protecting vulnerable population groups, such as children, from exposure to groups of chemicals with known hazardous properties.

Key messages

• Burden of disease calculations are well-established for air pollution but remain underdeveloped for chemical exposure.
• Ongoing case studies on substances like lead, arsenic, pesticides, and PFAS are addressing this critical knowledge gap.
• These studies aim to develop policy indicators to assess health impacts and provide strategies to reduce them. 

Overview

Environmental burden of disease analyses how much disease is caused by environmental factors like chemical exposures, while health impact assessments estimate the health effects of policies or programs. Together, these analyses help identify priorities for preventive action for current chemical exposure in the EU ↗. Case studies on priority substances identified by the Partnership for the Assessment of Risks from Chemicals (PARC) will calculate health impacts, risks, and cost scenarios, depending on data availability and methodological improvements. Findings will support the creation of indicators for risk and health impact.  

Health impact assessments as well as social and external cost-benefit analyses help quantify the health impacts of chemical exposure across EU populations. These tools can prioritise actions to prevent or reduce exposure and estimate the environmental burden of disease and the avoided costs due to policies and regulations. 

Case studies will focus on key chemicals prioritised by PARC. Based on findings from related projects in PARC on data and methods, selected case studies will assess health impacts and risk or cost-benefit scenarios for certain chemical, chemical classes, mixtures ↗, adverse health effects, and affected populations, using both existing and newly generated data. The results will also contribute to a project dedicated to developing a set of risk and health impact indicators. 

This project is one of four interconnected initiatives focussed on assessing the health impacts of chemical exposure. 

Achievements & Results

In the first year, a framework was developed to prioritise chemical exposure case studies. This included creating criteria and scoring rules, which were applied to proposals from project partners to select the most relevant studies. Initial case studies were identified, and their design and implementation are now ongoing.

For the second year, the focus is on finalising the first set of studies and beginning their implementation. These studies aim to assess health impacts, including burden of disease and cost-benefit analyses. Plans are also underway to prioritise additional case studies for future years, targeting key health effects like endocrine disruption ↗, immunotoxicity ↗, and neurotoxicity ↗. Work will continue to improve methods and harmonise approaches across studies. 

Key messages

• It is relatively difficult to identify occupationally exposed groups from the general population data.
• In order to be able to identify potential occupational exposed groups from general population surveys, it is of utmost importance to have a high enough sample size with ISCO-coded information on occupations. This means that data from several national studies needs to be combined.
• ISCO-08 encoding of occupations with at least 4 digits is needed to get meaningful results. This requires that detailed data on occupations and job descriptions are collected as part of general population surveys.

Overview

This project uses human biomonitoring data from the European Human Biomonitoring Initiative (HBM4EU ↗) to examine occupational exposure to chemicals like cadmium ↗, chromium ↗, PAHs ↗, and bisphenols ↗. The goal is to determine whether data from general population studies can reveal elevated exposure levels among workers compared to non-occupationally exposed population groups. It is designed as a short-term feasibility (pilot) study but the results may help improving the design of future general studies in future, provide further information for improving exposure assessments and support regulatory frameworks in Europe, including the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH ↗) and Occupational Safety and Health (OSH ↗), to better identify and manage occupational health risks.  

By developing an approach to analyse HBM4EU general population data, this study aims to identify groups that are occupationally exposed to higher levels of harmful chemicals. It furthermore seeks to evaluate how general population studies, focused on adults can detect these elevated exposure levels. The results may also help to explain the variability observed in the general population biomonitoring data.  

The results of this feasibility study will be valuable for future human biomonitoring research on the general population. Thus, researchers conducting these studies will be among the key beneficiaries of the findings.  

The regulatory outcomes of this project can contribute to both REACH and OSH processes. When general population human biomonitoring data is used for exposure and risk assessments, it is crucial to identify the primary sources of exposure. If occupational exposure is a potential confounding factor, it needs to be detected and accounted for to avoid distorting the results. At the same time, the data may contribute to occupational exposure assessments under REACH and OSH processes.  

Since this is a feasibility study aimed at proving the concept, there is no need to align the project’s timeline with existing policy agendas.  

Achievements & Results

In the first year, relevant studies were identified, and initial work on selecting studies and coding occupations began. By the second year, agreements with data owners were finalised, but data analyses awaited access to datasets, and coding of occupations continued.

In the third year, data analyses for the International Standard Classification of Occupations 2008 (ISCO-08 ↗) coded datasets were completed, conclusions were drawn, and a report was finalised and a publication on the results is planned for the second half of 2025.

Policy relevance

Improves our understanding on the human exposure to chemicals, including occupational exposure. By doing so, it supports EU legislation on the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) and Occupational Safety and Health (OSH) legislation in EU.

Overview

Monitoring chemicals in the environment is crucial to understanding their impact on human health and ecosystems. It helps identify where these substances come from, how widely they are spread, and whether stricter controls – such as limiting or banning their use – are needed. Monitoring also provides essential data to evaluate the effectiveness of measures taken to reduce pollution, aligning with the European Union’s Zero Pollution ambition ↗. However, monitoring is a complex, time-consuming, and costly process, requiring careful planning to focus on the most pressing issues while ensuring no harmful substances are overlooked.

This project aims to address these challenges by developing a flexible system to prioritise which chemicals need closer monitoring. It focuses on chemicals that are poorly monitored or entirely overlooked, including unintentional mixtures and new substances of emerging concern.

By creating a transparent, and reproducible framework, this project will help identify priority chemicals, environmental areas which are known as matrices, and specific health or ecological effects for targeted monitoring. Matrices are parts of the environment, like water, soil, or air, where pollutants can accumulate.

This framework will ensure that monitoring efforts are efficient, effective, and aligned with regulatory needs. It will also be adaptable to emerging risks and changing environmental challenges, helping to safeguard human and environmental health while supporting the EU’s goal of reducing pollution.

Overview

Over the years, various tools and database platforms have been created to store, analyse, and visualise data and trends on the presence of chemicals and trends in their exposure in the environment. However, each tool or platform was developed for different user groups, offering various services and addressing different topics. The available data is often organised by type of environmental sample (such as water, air, or soil), and these datasets vary in content, structure, and development, including differences in data standardisation, classification systems, and available tools.

The environmental monitoring and exposure component of the Partnership for the Assessment of Risks from Chemicals (PARC) focuses on studying how chemicals move and accumulate in multiple parts of the environment. It also examines how humans are exposed to these chemicals when they originate from different sources and travel through various pathways.

This research promotes a “one health” approach to chemical risk assessment, which considers the interconnected health of people, animals, and ecosystems. Researchers will evaluate combined exposures by analysing the presence of chemicals, their breakdown products, and their interactions across different environmental samples.

Members of the research and innovation teams in PARC are seeking better ways to access and connect existing data resources, such as monitoring programs, databases, and scientific libraries. These solutions will help map and access the diverse information already available. By gathering and combining information on chemicals in the environment, researchers aim to improve how risks to human health and ecosystems are assessed.

Overview

Establishing a process for environmental and multisource monitoring is a key focus of the PARC initiative. This process aims to support the European Union's chemical risk assessment efforts by addressing two main areas: (i) environmental ecosystems ↗ and (ii) human exposure ↗, closely linked to human biomonitoring.

Building on existing structures and knowledge is a prerequisite for achieving these goals, making environmental and multisource monitoring a complex but essential task that requires highly optimized processes to maximize its benefits.

As part of this effort, a pilot project will be launched to focus on per- and polyfluoroalkyl substances (PFAS) and endocrine disruptors. PFAS – also known as “forever chemicals” – are a group of synthetic chemicals found in various products that persist in the environment and the human body, while endocrine disruptors are substances that can interfere with hormonal systems, potentially causing adverse health effects. The pilot project aims to establish and validate environmental monitoring structures. In addition, the project will include a review of cutting-edge methods and the development of a study design for monitoring these substances.

Key messages

Reach a common understanding of what needs to be improved in the environmental risk assessment for plant protection products, such as the need to:

• Overcome the limitations of the current substance-by-substance approach,
• Adopt a more realistic consideration of the environmental context.

Address issues related to improving environmental risk assessment for plant protection products through the related research projects.

Overview

The project seeks to improve the prospective evaluation of the effects of plant protection products on biodiversity by simplifying environmental risk assessments ↗ and enhancing the level of protection. This will be achieved by overcoming the limitations of the current substance-by-substance approach and adopting a more realistic consideration of the environmental context and a more holistic approach. The project will compare current methods with new ones and cross-check both against independent environmental monitoring data.

The project also aims to explore more holistic approaches to risk assessment. This means evaluating environmental risks in a broader context rather than focusing on individual substances in isolation. By doing so, it considers how multiple factors interact under real-world conditions.

In addition, the project will review and refine existing models while developing new ones for risk assessment. It will also create new frameworks for risk characterization, supporting approaches that assess entire systems rather than isolated components.

The main objective of the project is to establish a more effective and efficient way to assess environmental risks by optimizing the use of data, knowledge, and expertise, as well as resources. This will also strengthen collaborations and improve overall risk assessment strategies.

Achievements & Results

Main activities aimed at better describing the challenges and needs for an improved environmental risk assessment of plant protection products:

• Establishing dialogue and connections between various research projects and stakeholders, while also considering publicly available documents.
• Collaboratively defining the term systems-based environmental risk assessment, which encompasses the entire system rather than isolated components.
• Conducting surveys and online workshops to better understand the needs of risk assessors in this field, supporting the transition towards more integrative approaches.

These activities have helped define what needs to change in the environmental risk assessment of plant protection products—“designing the right things”—before implementing the findings in the related research projects to “design things right.”

Policy relevance

The improved regulatory framework for plant protection products will be better aligned with new policy targets, e.g., European Green Deal ↗, the EU “Zero pollution ↗” ambition, and EU and national chemical risk assessment and risk management bodies. 

Key messages

• The project will illustrate the usefulness of early warning monitoring tools both for environmental and biomonitoring;
• Criteria for acceptance and prioritization of early warning signals will be defined.

Overview

This project is supporting the establishment of an Early Warning System (EWS) to identify and prioritise new and existing potentially hazardous substances, addressing key needs in EU regulatory policies ↗ and chemical risk management ↗. It is ensuring that data generated by innovative methods – including non-targeted screening combined with effect based methods – are used to detect substances that may pose risks to human health and the environment.

By demonstrating the usefulness of EWS tools in various types of samples – environmental samples (e.g. soil, sediment, dust), animals (e.g. fish), human samples (e.g. blood), food (including drinking water) and consumer products (such as waste streams and recycled materials) - the project is highlighting their broad applicability.

Chemicals and toxicological data are created and shared in databases. Computational tools can be used to evaluate their exposure and hazard characteristics to allow substances to be prioritised based on their potential risks.

By improving detection and prioritisation, the project is strengthening the EU's capacity to respond to emerging chemical threats. It is supporting evidence-based decision-making, guiding regulatory action and ultimately improving chemical safety to better protect people and the environment.

Achievements & Results

• The project will illustrate the usefulness of early warning monitoring tools both for environmental samples (e.g. soil, sediment, sludge, dust), human samples (e.g. blood), food (incl. drinking water) and products (incl. waste streams, recycled products).
• The project will identify in particular chemical properties, toxicological endpoints and high resolution mass spectrometry features relevant for the EWS.
• Criteria were formulated for the categorisation of annotated data to be integrated in the EWS format.
• A perspective article on innovative approaches as a contribution to an EWS will be published.
• This project will generate proofs-of-concepts and tools of relevance to risk assessors and policy makers at national and EU level contributing to an EU EWS and supporting EU agencies (EEA ↗, EFSA ↗, ECHA ↗).

Policy relevance

Innovative (self-)sampling combined with integrated suspect, nontarget screening and effect directed analysis approaches are of utmost importance for identification of new and existing potentially hazardous substances at an early stage. Cutting edge tools will be conceptualised and illustrated for establishment of an EWS and contribute to early warning system and harmonised framework from environment-food-human. End-users include ECHA, EFSA, EEA, national environmental and chemical agencies, national food safety authorities, NORMAN network ↗, researchers, industry, NGOs, national consumer protection organisations and the general public.

Overview

Wastewater and wastewater plants are important sources of information for advancing scientific understanding of human exposure to chemical substances. By measuring specific markers, such as human metabolites, in wastewater in wastewater treatment plants, we can significantly contribute to a better management of chemicals that threaten both public health and the environment,  

This project focuses on studying wastewater with an emphasis on both human and environmental exposure. It employs innovative methods including (i) wastewater fingerprinting for assessing community wide human exposure and (ii) screening of wastewater treatment plant effluents to assess the release of Chemicals of Emerging Concern into the water cycle ↗. While utilising wastewater-based epidemiology tools, further presence of pathogens ↗, chemicals ↗, and other indicators of health in a community can be monitored. These commonly arise from substances like viruses, bacteria and pharmaceuticals ↗being excreted by individuals through urine and feces, which then enter the sewage system.  

The methods used in this study can contribute to the establishment of a European scale monitoring system and facilitate the re-evaluation of existing data, greatly extending the knowledge base on Chemicals of Emerging Concern in the water cycle.

This research will serve as a basis for revising and managing several water related legislations, such as the Urban Wastewater Treatment Directive ↗, with to the goal of reducing emissions of Chemicals of Emerging Concern. Additionally, it will provide information on river-basin-specific chemicals for the Water Framework Directive ↗. Furthermore, the study will provide information on chemical mixtures ↗, supporting the revision of the European regulation Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH ↗). 

Achievements & Results

The results of this project will be disseminated toward the conclusion of the project timeline, in alignment with planned milestones. However, a significant achievement has already been realised with the successful implementation of the first pan-European sampling campaign as scheduled for 2024. 

Policy relevance

This research uncovers the need to revise European legislation on water management.

Key messages

This project will explore the potential of animal species, in particular gammarids and bees, as sentinels of the chemical status of the environment and the human food chain, using innovative screening methods based on advanced high-resolution mass spectrometry and effect-directed analysis. 

Overview

Capturing the complexity of real-world chemical exposure of humans and the environment requires new conceptual frameworks and innovative methodological approaches. Within PARC, suspect and non-targeted screening based on high-resolution mass spectrometry ↗ coupled with effect-directed analysis, is emerging as a promising strategy for this purpose.  

Aligned with the One Health concept ↗, various animal sentinel species can provide  valuable insight into chemical exposure risks for both humans – particularly through the food chain – and environmental ecosystems. Bioaccumulation capacities are especially valuable, as they may exhibit higher concentrations of chemicals than those typically found in human biological samples, thereby enhancing detection sensitivity.

This project will focus on marine and terrestrial sentinel species, such as  gammarids and bees. These animals can often be sampled more easily than humans, especially when specimens are already available in existing biobanks. The aim is to develop and conduct a proof-of-concept study to assess the relevance and effectiveness of using sentinel species in combination with innovative screening methods. These approaches will serve as a complement to conventional and targeted analyses, supporting the development of an early warning systems for chemicals of emerging concern. Ultimately, the project aims to provide evidence for food and environmental policy-makers to strengthen chemical safety and health protection strategies. 

Achievements & Results

The project has been divided into three actions. First, a review article on the concept of sentinel animal species will help identify the key points for each species. The scope has been defined, and the literature query is under optimization. Second and third, sample sourcing is on-going for gammarids and bees, within the biobank of the Swedish National Marine Monitoring Program and the European network of National Reference Laboratories for Bee Health ↗. 

Policy relevance

This project, like others within PARC, will provide first insights in occurrence data on large numbers of not yet regulated/monitored chemicals and not yet known chemicals. Policies related to the human food chain (e.g., general food law Reg 178/2002) and environmental aspects are targets (e.g. Marine Strategy Framework Directive 2008/56/EC). 

Overview

This project targets siloxanes, especially the cyclic volatile methylsiloxanes (CVMS) D4, D5 and D6 ↗, and selected linear volatile methylsiloxanes (LVMS), due to their high production volume and widespread in industrial and consumer use. These substances are recognised for their environmental persistence, bioaccumulation, and toxicity. Regulatory actions under REACH ↗ have already restricted their use in cosmetics, and discussions are ongoing about their classification as persistent organic pollutants (POPs) under the Stockholm Convention ↗.

To support future regulatory efforts, the project aims to generate high-quality environmental monitoring data on CVMS and LVMS. It addresses key knowledge gaps in their environmental fate, especially in air and wastewater, and explores their potential for long-range transport. The first project phase will assess the feasibility of robust siloxane measurements by reviewing and testing available sampling and analytical methods. Given the complexity of measuring siloxanes due to contamination risks and instability in sampling media, this phase is crucial to establish analytical reliability.

If successful, the second phase will implement a targeted monitoring campaign. Air, water, sediment, and biota samples will be collected to understand deposition pathways and environmental transport mechanisms. This work directly responds to identified regulatory needs in the Key Areas of Regulatory Challenge ↗ (KARC) and contributes to PARC’s future activities. It also supports improved risk assessments by focusing on environmental exposure and excluding biomonitoring, which remains analytically difficult for siloxanes. The project’s results will help inform EU-wide decisions and ensure appropriate regulatory action for siloxane management.

Overview

Although strict regulations govern the use of agricultural pesticides ↗ in Europe, field studies have revealed harmful effects on non-target organisms, which include species not intended to be affected by pesticides. This goes against European regulation ↗, which requires that pesticide use does not harm the abundance or diversity of these organisms. This project aims to improve the way environmental risks are assessed by considering the combined effects of multiple pesticides and other stressors on a broader landscape scale, rather than focusing on individual chemicals and crops.

A landscape-level approach takes into account how different types of agricultural land use, such as fields, forests, and water bodies, interact with pesticide exposure. It also considers the vulnerability of populations living in these environments.

Given the complexity of such large-scale assessments, the project will focus on identifying the most important factors – referred to as “drivers” – that influence pesticide exposure and its effects on the environment.

To achieve this, the project will build on findings from three earlier studies to develop models tailored to different types of landscapes. These models will include recommendations from the European Food Safety Authority (EFSA ↗) to set protection goals based on safeguarding ecosystem services, such as pollination ↗, and preserving biodiversity ↗. The ultimate goal is to create tools that provide a clearer and more consistent way to assess environmental risks, addressing current gaps and inconsistencies in existing methods.

Achievements & Results

The interlaboratory exercise was designed through a collaborative process involving all project partners. An online survey and a detailed questionnaire were used to gather input, ensuring that the design reflected a broad consensus and addressed the needs of all involved laboratories.

• The project will leverage outcomes from other projects that compare predictions with monitoring data, enhancing the feedback loop from environmental monitoring to focus on factors impacting biodiversity in both terrestrial agro-biosystems and aquatic ecosystems.
• It will support regulatory decisions and the design and implementation of National Plans under the Sustainable Use Directive, aiming to provide management tools for informed decision-making in Integrated Pest Management and ecosystem restoration.
• Conceptualization of Landscape risk assessment: Four workshops held between November and December 2022 included partners, external experts, and EFSA. Minutes were compiled and distributed for comments, and key elements for Landscape-ERA were extracted.

Identification of the case studies: Several partners proposed case studies, with some confirmed and others pending. The design process for case studies is ongoing, with the next step being the adaptation of the conceptual model to each case study.

Key messages

• Assessment of reproduction and embryotoxicity in pond snails by mycotoxins commonly present in wastewater
• Assessment of cyanobacterial toxicity to marine and freshwater invertebrates on life history
• Assessment of cyanobacterial toxicity in combination with chemical pollution to green algae 

Overview

The EU uses regulations as a method to set threshold values for the concentration of natural toxins such as microcystins ↗, yessotoxin ↗ and saxitoxin ↗ to ensure they remain safe for human consumption. Microcystins are toxins produced by cyanobacteria ↗ in freshwater, while yessotoxin and saxitoxin are marine biotoxins associated with harmful algal blooms.

While there are regulations in place to protect human health, there is a gap in regulations regarding safe exposure levels for aquatic species from an environment health perspective.

In aquatic ecosystems, invertebrates have a crucial role in the food chain and the overall functioning of the ecosystem, as they are primary consumers and serve as food for higher trophic levels. Microalgae are in turn the primary food source for these invertebrates, which are positioned on an even lower level in the trophic chain forming the very base of aquatic ecosystems. Studying the effects and risks natural toxins have on aquatic organisms, such as invertebrates and microalgae, lays the cornerstone of assessing the need for regulations and toxin mitigation measures.

By investigating the toxicity of naturally occurring toxins alone or in combination on aquatic organisms, this project aims to make an impact on the regulatory landscape concerning the protection of marine and freshwater environments. Within EU legislation, this project draws on the Marine Strategy Framework Directive ↗ and the Water Framework Directive ↗. Additionally, the results of this project will also serve as a basis for further regulating nitrogen and phosphorus pollution ↗ within the EU, as these contribute to eutrophication ↗, a key driver of harmful algae bloom.  

Achievements & Results

The study investigated the effects of various natural toxins and environmental conditions on aquatic organisms. Here are the key findings:

• Toxicity of Mycotoxins: Several mycotoxins commonly found in wastewater, such as zearalenone and deoxynivalenol ↗, were tested for their effects on pond snail embryos. Toxicity levels were detected at concentrations well above environmental levels.  
• Impact on Tiny Crustaceans: Two marine toxins, yessotoxin and saxitoxin, were shown to reduce the number of offspring produced by the estuarine copepod N. spinipes. This impact became even stronger when water temperatures were elevated, highlighting the potential risks of climate change in amplifying toxin effects.
• Toxin Levels in Natural Waters: Measurements of four algal toxins in natural seawater (yessotoxin, saxitoxin, domoic acid, and microcystin-LR) found that, in the absence of algal blooms, their concentrations are below levels shown to cause harmful effects in this study.
• Effects on Green Algae: Testing the effects of microcystin-LR and cylindrospermopsin on green algae (C. vulgaris) revealed that growth was affected only at relatively high concentrations (4 to 40 mg/L) after 4 to 7 days of exposure. 

Policy relevance

• Drawing attention to the need of further regulations on threshold values of naturally occurring toxins in the aquatic environment
• Providing scientific support to prioritize specific toxins and sensitive species across marine and freshwater habitat based on effect assessments 

Key messages

• Consistent risk assessment requires that risks of compounds can be compared and ranked
• Evaluation of current approach and development of concepts and methodologies to improve comparability
• Risk assessment outcomes should also hold against relative risks of compounds identified in real world studies 

Overview

This project aims to demonstrate that environmental risk assessments ↗ of plant protection products, often referred to as pesticides ↗, can be used as benchmarks to evaluate the risks of other similar products. The process involves comparing and ranking the environmental risks of different plant protection products across various substances and groups of organisms, ensuring that all assessments follow the same level of refinement. By developing new concepts and methodologies, the project seeks to make individual risk assessments more comparable and consistent, which will improve their reliability when matched against real-world monitoring data and lead to more accurate environmental risk estimations.  

A key goal is to create a more comprehensive approach to environmental risk assessments that manages risks more effectively. The project will analyse existing data sets and case studies of products rejected during regulatory assessments. This will allow for both internal comparisons within a product’s risk profile and external benchmarking against other products. The findings will help identify weaknesses in the current environmental risk assessments system and propose immediate solutions. Over time, the project will develop a compatibility methodology aligned with the future environmental risk assessments framework envisioned by the Partnership for the Assessment of Risks from Chemicals (PARC) partners. Ultimately, these efforts aim to significantly improve the environmental risk assessments process under European regulation ↗, ensuring better protection for ecosystems and public health. 

Achievements & Results

• Investigated the heterogeneity of higher-tier data, leading to the preliminary conclusion that this would be a challenge to benchmarking plant protection products (a pre-print is available).
• Identified and highlighted the environmental risk assessment factors determining the rejection of a PPP under the EU regulatory framework EC No. 1109/2009.
• Conceptual Plant Protection Products Benchmarking Paper with the working title “A Benchmarking Framework to Improve the Quality and Expedience of Regulatory Environmental Risk Assessment for PPPs”
• Development of an internal risk benchmarking framework concept for plant protection products.
• Creation of database containing EU-authorized active substances for insecticides and acaricides, their toxicity endpoints, predicted environmental concentrations and other exposure data, environmental fate, mode of action and representative uses.
• The project will produce an environmental risk assessment concept and methodology to develop new guidance for environmental risk assessment within the authorization process. This environmental risk assessment will enhance the ability to capture the relative risk of different plant protection products across relevant spatial and temporal scales, using similar data and levels of refinement.  

Policy relevance

Environmental risk assessment is an important area contributing to a sustainable use of plant protection products as demanded by the Sustainable Use Directive and also contributes to meet biodiversity targets through a more efficient management of environmental risks.

Overview

Innovative approaches to chemical risk assessment are vital for achieving the European Union's Chemicals Strategy for Sustainability ↗ and Green Deal ↗ goals. This project focuses on advancing New Approach Methodologies ↗ (NAMs) – innovative tools for assessing chemical risks to human health and the environment – by addressing challenges such as complex chemical effects and knowledge gaps.

The project reviews how these methods are currently developed and used, consulting experts and analysing scientific literature to identify barriers like technical, legal, and cultural challenges. Despite scientific progress, integrating these tools into regulations has been slow due to limited alignment with regulatory needs. To address this, the project will establish criteria for accepting these methods, create guidelines for their use in daily workflows, and conduct case studies to demonstrate practical applications.

By collaborating with similar initiatives in Europe and the United States, the project will enhance knowledge sharing and ensure the methods are applicable across regions.

The outcome will promote the wider adoption of innovative risk assessment tools, supporting sustainability and regulatory harmonisation while protecting human health and ecosystems.

Achievements & Results

• Structured interviews with risk assessment experts were completed.
• Development and pilot testing of online questionnaires is ongoing.

This will enable to:

• Conduct a landscaping exercise to evaluate the integration and use of NAMs across sectorial frameworks, highlighting current implementation status and challenges.
• Identify gaps, needs, barriers, opportunities, and drivers for integrating NAMs into regulatory practices, outlining a roadmap for their application at desk level.
• Develop an action plan for prioritising regulatory-relevant scenario-based case studies, informed by international workshops, to demonstrate the practical utility of NAMs in diverse regulatory contexts.

Key messages

• The scientific basis of the pesticide environmental risk assessment needs to be strengthened, and the regulatory complexity needs to be bechmarked;
• The validation status of exposure models in the environmental risk assessment of pesticides needs to be improved;
• Measured and predicted environmental pesticide concentrations have to be contextualized to assess the real exposure situation;
• The overall aim is the optimization of complexity within the regulatory exposure assessment of pesticides to ensure protectiveness.

Overview

This project is part of PARC Activity “Risk assessment to support and promote efficient overall protection of biodiversity”, which focuses on enhancing environmental risk assessment (ERA) methods. The aim of this project is to investigate the potential for simplifying and improving the predictions in the exposure assessment of the authorization process for plant protection products (PPP, commonly known as pesticides) under Regulation (EC) No 1107/2009. The current process is intricate and resource-intensive, prompting to optimize the space between necessary model complexity to achieve a protective predictive capacity and regulatory feasibility. The focus is on the ERA of pesticides with the long-term aim to expand the scope to support chemical ERA in general.

During Y 1-3, this project performed an extensive “reality-check” of the exposure predictions based on a comparison of predicted environmental concentrations (PECs) from a range of exposure models with measured environmental concentrations (MECs) from monitoring studies in various European countries, benchmarking the complexity of regulatory PEC models.

Initial results give no indication that complex models provide more accurate predictions of maximum MECs than simple models based on assumed key risk drivers, demonstrating that data-driven model refinement, grounded in real-world environmental monitoring and sensitivity analysis, can lead to more efficient and protective models.

Going into Year 4, PEC model analyses and model parameter sensitivity analyses will be continued; European MECs will be analyzed in more detail, considering e.g., national-level regulatory specificities and pesticide application. “Real” environmental concentrations (RECs) will be approximated and explored to optimize the comparison and assessment of protectiveness of PECs.

Policy relevance

The goal of of this project is to strengthen the scientific basis of ERA and to develop a clear risk profiling system for pesticides based on the investigation of available MECs in concert with the evaluation of PEC models and factors influencing their predictive capacity for the real exposure situation in the field (RECs). Contextualizing these exposure assessment-related aspects and assessing their transferability across different member states will provide insight into the state of realism and protectiveness and concrete improvement opportunities for chemical ERA.

Overview

This project aims to simplify and improve the process of assessing the environmental risks of plant protection products, such as pesticides. While these assessments have become more complex and resource-intensive, real-world studies still show harmful effects on ecosystems. These findings conflict with European regulations, such as the regulation on the uniform principles for evaluation and authorisation of chemical plant protection products ↗, which is designed to protect the diversity of species that are not targeted by pesticides but still may suffer damage because of exposure to it.

The project seeks on enhancing the environmental risk assessment ↗ by using data and methods that have been tested through ecosystem monitoring and effect modelling. Monitoring ecosystems means observing real-world impacts on plants, animals, and their environments, while effect modelling involves creating simulations to predict how products might harm ecosystems. This approach helps improve how well laboratory results can be applied to real-world conditions.

One of the tools being used is the stress addition model ↗, which predicts how different stress factors, like chemical exposure, combine to impact ecosystems. The model will be tested against actual monitored ecosystem data to ensure it is reliable.

The research also looks at how these products affect species differently, depending on their mode of action, which refers to how a chemical works to kill or control pests. By focusing on specific species groups, the project will create a more realistic and effective environmental risk assessment framework.

To make these improvements accessible, the project will develop a user-friendly software package. This tool will help create clear and reproducible risk assessments that can be used across different regulatory systems.

Achievements & Results

• Collation of field monitoring data on plant protection product exposure and effects from multiple EU member states, initially focusing on Germany, Sweden, and Switzerland, with plans to incorporate data from diverse regions to reflect European variability.
• Formalisation of a feedback loop between current risk assessment thresholds and retrospective ecosystem monitoring results to enhance realism and validation of the environmental risk assessment process.
• Enablement of regulators to identify and integrate crucial ecological processes into the risk assessment framework based on comprehensive field monitoring data across European regions.

Key messages

• Investigation of the potential adverse effects (e.g. apical endpoints such as mortality, effects related to the anticipated mode of action or MIE, effects on reproduction, effects on endocrine system) of certain individual substances and “real-life” mixtures of BPA alternatives on non-mammalian organisms belonging to different taxa  
• The project is dedicated to developing innovative New Approach Methodologies (NAMs) to identify chemical hazards with respect to the environment.
• The methods under development cover a wide range of taxa across the phylogenetic tree and address diverse endpoints and approaches. 

Overview

Concerns about the harmful effects of bisphenol A (BPA) ↗, a chemical commonly used in plastics, and strict restrictions on its use in many countries have led to the development of alternative chemicals.  These substitutions, known as BPA alternatives, are now emerging as environmental contaminants found across the globe in water, sediment, sludge, soil, indoor dust, and air. The upcoming opinion from the European Food Safety Authority (EFSA ↗), which recommends significantly reducing daily BPA exposure, is expected to increase the use of these alternatives further.  

Many BPA alternatives share similar properties with BPA. They are often toxic to aquatic organisms, can disrupt endocrine ↗ (hormonal) systems, affect reproduction, metabolism, and immune systems, and may persist in the environment.

BPA alternatives are regulated under the European Union’s REACH ↗ framework, which governs the safe use of chemicals. However, the data required for assessing the safety of those alternatives vary depending on the production volume, and existing information is often insufficient to fully evaluate their potential risks to humans and the environment. The risks posed by exposure to mixtures of these chemicals ↗—common in real-world scenarios—are particularly underexplored, especially for long-term effects at environmentally realistic concentrations. This research project seeks to address these gaps by studying the potential harmful effects of BPA alternatives on various organisms. It will also develop new methods and tools for assessing these chemicals, with a focus on improving regulatory approaches and environmental safety. 

Achievements & Results

Tests with individual compounds have been conducted, revealing that the toxicity of bisphenols varies, with some being more harmful than others. The observed effects are dependent on the specific test organism or system used. Discussions are ongoing regarding the mixtures to be tested in the next phase.

As part of the project, experts conducted an extensive review, sharing their insights on the toxicity of BPA alternatives and their presence in the environment. The article can be accessed here ↗.

The project is also advancing innovative methodologies aimed at replacing traditional vertebrate animal tests. This includes the development of high-content screening techniques using zebrafish embryos and the creation of 3D zebrafish spheroids. 

Policy relevance

• Filled data gaps: Investigation of the toxicity of bisphenols in organisms belonging in different taxa, in some cases different than the ones required by the European regulation.  
• Identification of safer than BPA bisphenols or other alternatives.  
• Investigation of the effects of bisphenol mixtures    
• Improved hazard identification: NAMs utilizing environmental models provide precise data on the ecological effects of chemicals across diverse taxa, enabling regulators to identify hazards efficiently without extensive animal testing.
• Ethical and sustainable practices: New NAMs reduce reliance on animal testing, aligning regulatory practices with ethical standards and global sustainability goals while ensuring robust environmental safety evaluations.
• New methods investigating toxicity for environmentally relevant models help better understand chemical risks that are necessary for the implementation of preventive measures and enforce regulations that minimize chemical risks.

Key messages

• Endocrine disrupting chemicals (EDCs) can cause long-lasting changes to how our bodies manage energy and fat storage – what scientist call metabolic disruption.
• Chemicals suspected to trigger these changes are known as metabolism-disrupting chemicals. They may contribute to obesity, type II diabetes, and non-alcoholic fatty liver disease.
• Our project develops and improves new approach methodologies (NAMs) to identify and assess metabolism-disrupting chemicals. These include: nuclear receptor models; in vitro test using fat (adipocyte) or pancreatic cells; whole organism test systems, i.e. a zebrafish embryo/larval assays.
• We found that some Bisphenol A alternatives – candidates for safer replacement – can still disrupt metabolic pathways.

Overview

Over the past decade, research into endocrine-disrupting chemicals ↗ – substances that interfere with the body's hormonal systems – has revealed that some of these chemicals can cause long-lasting disruptions to metabolism. These substances are now referred to as "metabolism-disrupting chemicals." They are strongly suspected to contribute to the development of metabolic disorders such as obesity, type II diabetes, and non-alcoholic fatty liver disease. These health issues arise in combination with genetic factors, diet, and lifestyle choices. Currently, over 50 million people in Europe suffer from metabolic disorders, and the role of environmental factors, including man-made and natural chemicals, is increasingly recognised.

To classify a substance as an endocrine or metabolism disruptor, specific scientific criteria must be met, as outlined by the World Health Organization (WHO ↗). Despite growing evidence that these chemicals may contribute to the rise of metabolic disorders like obesity and diabetes, there are no dedicated laboratory tests yet that identify the harmful effects of metabolism-disrupting chemicals. This lack of tools makes it challenging to assess the risks these substances pose. Developing reliable methods to identify and evaluate these risks is critically important for public health and regulatory decision-making.

This project focuses on creating new approach methodologies (NAMs ↗) to address regulatory gaps. These methods will allow scientists to better identify and assess the risks associated with metabolism-disrupting chemicals. The substances under investigation include chemicals identified on priority lists by the Partnership for the Assessment of Risks from Chemicals (PARC) and European agencies such as the European Chemicals Agency (ECHA ↗) and the European Food Safety Authority (EFSA ↗). By expanding the scope of research to include experimental systems not yet explored and focusing on priority chemical families, this work aims to provide regulators with essential tools to tackle the health challenges posed by these harmful substances.

Achievements & Results

• Improved in vitro test methods by: expanding test chemical datasets; comparing to in vivo data; generating more human-relevant test systems, e.g. 3D cell systems; reducing animal-derived components in the test methods like fetal bovine serum.
• Developed a zebrafish larval assay ↗ that combines exposure to Western diets and aquatic exposure to suspect metabolic disruptors like bisphenol A.
• Screened bisphenol A alternatives for their impact on metabolic disruption.
• Obtained metabolism-disrupting chemicals mechanisms accross multiple levels of the adverse outcome pathway - from receptor interaction to whole organism effects.
• Published a state-of-the-art summary ↗ on metabolism-disrupting chemicals for the scientific and regulatory community.

Policy relevance

• WHO/IPSC (2002) outlines clear criteria classifying endocrine disruptors, but no official criteria yet exits for metabolism-disrupting chemicals.
• Metabolism-disrupting chemicals could potentially be regulated under similar frameworks as EDCs.
• To bridge this gap, validated NAMs are urgently needed.
• Our project develops fit-for-purpose methods that will help regulators detect and manage the risks of metabolism-disrupting chemicals.

Overview

Every day, chemicals are released into the environment leading to human exposure (e.g. through the food we eat, the air we breathe, and the products we use) and exposure of natural animal and plant populations. Many of these substances can interfere with hormone systems, potentially affecting our health and the environment. Identifying these endocrine disrupting substances, which can mimic, block, or interfere with hormones, is therefore crucial to ensure their regulation and guarantee public and environmental safety.

The objective of this project is to provide a framework for the creation of Integrated Approaches to Testing and Assessment (IATAs), which combine multiple sources of information to conclude on the toxicity of chemicals. Specifically, this project aims to develop IATAs for evaluating endocrine disruption, a priority health effect outlined in the European Chemicals Strategy for Sustainability ↗ priority areas: disruption of the thyroid hormone system, and anti-androgenic action. Disruption of either of these mechanisms can lead to important defects during embryonic development, which may persist later in life (e.g. leading to impaired cognitive function, or affected male reproductive health).

This project brings together researchers, regulators, and industry experts to refine the IATA frameworks.

By creating flexible, science-driven tools that are capable of adapting to different regulatory needs, this work will not only fill critical knowledge gaps but also ensure that decision-makers have the best possible tools to protect human health and ecosystems.

For this, a modular approach is envisioned to allow IATA adjustments to specific regulatory needs. This effort will not only structure and pinpoint key gaps but also facilitate the direct regulatory application of project outcomes.

Achievements & Results

Mechanistic IATA models identifying key mechanisms and effects involved in both thyroid and anti-androgenic endocrine activity and disruption, applicable for both human health and environmental protection and describing the links between them, were developed. The work utilised previously published OECD IATA approaches (OECD IATA guidance ↗; Jacobs et al. 2020 ↗; Louekari and Jacobs, 2024 ↗). Adverse Outcome Pathways (AOPs) available in the AOP wiki and a review of relevant literature were taken together and underpinned by expert knowledge. The OECD Conceptual framework (CF) for the identification of endocrine disruptors (OECD Guidance Document 150 ↗), which is also the basis of the EFSA-ECHA guidance on the assessment of endocrine disruptors, was applied and updated as appropriate. Method inventories for thyroid hormone system disruption and anti-androgenic activity were created, organised according to the differen OECD CF levels, annotated as a function of their readiness level, and aligned with the mechanistic models. Case studies were then developed describing how the IATA models may be implemented in selected, specific regulatory decision-making scenarios.

Policy relevance

Criteria for the identification of endocrine disruptors have been stipulated for the Biocidal or Plant Protection Products Regulations, and a guidance document, i.e. “Guidance for the identification of EDs in the context of Regulations (EU) No 825/2012 and (EC) No 1107/2009) ↗”, was written by ECHA and EFSA to guide identification of EDs to comply with these obligations. Endocrine disruptors for human and environmental health have recently been added as new hazard classes to the CLP (classification, labelling and packaging) regulation, and a Guidance on the Application of the CLP Criteria has been published by ECHA (ECHA, 2024 ↗). In that context there was a need to create an overview of available methods for the evaluation of endocrine disruptors for both human and environmental health, both validated methods and methods that are close to or under validation, and to structure the methods according to IATA development principles. A modular approach is envisioned to allow for tailoring an IATA to specific regulatory needs. An endocrine disruptor IATA framework could benefit all EU agencies and European regulators dealing with endocrine disruptor assessment (e.g. ECHA and EFSA, national regulatory authorities), as well as the different regulations addressing this hazard class thus contributing to the harmonization of data requirements among EU and member state agencies. This project will support better regulatory decision making and improve the hazard identification of endocrine disrupting chemicals with the long-term aim to limit exposure and improve human as well as environmental health. The use of predictive methods and NAMs will be explored, with the potential to significantly reduce the need for long-term, low-throughput and costly toxicity tests requiring large numbers of animals, thus contributing to the replacement of animal tests.

Key messages

• Mode of action data and curated effect concentrations for more than 3300 environmentally relevant chemicals are provided as FAIR data set for mixture risk assessments.
• 80 chemicals are ubiquitously released by European waste-water treatment plants and provide a cross-regulation mixture that should be regulated as background baseline pollution in European riverine systems.
• Austrian groundwater monitoring data were clustered to identify potential mixtures, identified mixture risk drivers were also assessed in drinking water to assess a potential health risk for humans.

Overview

This project focuses on improving how we assess and manage the risks of chemical mixtures ↗ to better protect human health and the environment. Currently, most regulations evaluate chemicals one by one, but people and nature are exposed to multiple chemicals at the same time. For mixture risk assessment, information on co-exposures and potential effects of all individual mixture components is required. This project aims to provide data and approaches to derive such data on a European scale, to deal with respective datasets, and to extract relevant information that can be applied and standardised for chemical mixture risk assessment.

A key part of the project is the collection and analyses of chemical monitoring data and the identification of mixture risk drivers, their heterogeneity, the derivation of potential reference mixtures for regulation, and the provision of data sets suitable for large scale mixture risk assessments. Next to monitoring data and co-exposure information, effect data for chemicals generated with New Approach Methodologies (NAMs) as well as mode-of-action information will be included and considered within mixture risk assessment approaches to accompany and support ongoing activities on chemical grouping for mixture risk assessments.

By testing and refining these approaches, the project aims to improve how chemical risks are evaluated and managed.

Key research questions are:

• How can representative reference mixtures be developed and applied?
• How can mixture risk drivers be identified and how many of them do we need to deal with?
• Where are the largest data gaps and challenges for comprehensive mixture risk assessment?
• Which chemicals should be considered jointly also cross regulation due to unintended co-occurence?
• How can NAM data provide a comprehensive picture of chemical exposure for risk assessment?

Key messages

• The battery of genotoxicity in vitro assays is sensitive for the detection of genotoxic carcinogens, but the multifactorial nature of the carcinogenesis process greatly hinders the detection of non-genotoxic carcinogens.
• The overarching aim of this project is to improve human carcinogenic evaluation in vitro based on reliable and relevant new approach methodologies (NAMs), ultimately enabling a better prediction of human risk in line with regulatory requirements. 

Overview

This project aims to advance the identification of non-genotoxic carcinogens ↗ (NGTXCs) by applying innovative, human-relevant NAMs to a range of organ and cellular model systems, including liver, breast, colon, and adipocytes. Techniques such as transcriptomic, high-content analysis, cell painting, epigenetics, and high-throughput-compatible reporter systems will be used to investigate key mechanisms of carcinogenesis, including oxidative stress, epithelial-mesenchymal transition, inflammation, changes in metabolism, epigenetic marks or nuclear receptors signaling and cell proliferation.

In addition, in silico tools will be optimised to support the identification of substances acting through non-genotoxic carcinogens, addressing the needs for the development of an Integrated Approach to Testing and Assessment ↗ (IATA) for NGTXCs. This work is carried out in collaboration with IATA and aligns with ongoing EU and OECD activities.

The project will contribute to a better understanding of the links between specific substances and adverse outcome pathways (AOPs) that lead to cancer. It will also evaluate methods of increasing biological complexity, from traditional 2D cell cultures to 3D spheroids and zebrafish models to integrate physiologically relevant toxicological information.

By comparing the different assays, the project will define the applicability domain and limitations of each method. This will ultimately inform chemical risk assessment and regulatory decisions, aligning with international efforts on NGTXCs and supporting the development of more predictive, ethical and efficient safety assessment strategies. 

Achievements & Results

All partners finalized the testing of the first set of reference substances (at least 4 positives and 4 negatives) and at least two (up to 10 substances) for each of the 5 different selected mode-of actions: proliferation, oxidative stress, nuclear receptor activation, inflammation and changes in cellular morphology indicative for cell migration as well as cytotoxicity that might be indicative for regenerative proliferation. The data was reported in an already agreed common data template for each chemical.

The analysis of tissue, model and substance specific effects related to distinct aspects of carcinogenesis is ongoing, including a comparison of the lowest concentration needed to detect a significant and/or potentially biological relevant effect in the various test systems. This will facilitate the (further) development of prediction models for each assay to especially define thresholds that allow identification of physiological/ biological and regulatory relevant activities and to develop a complementary and predictive test battery.  

However, some more complex methods are still in a status of development and optimization, in particular different 3D liver organoids that include liver cells, macrophages and stellate cells and a 3D mammary duct model. 

Overview

Enhancing the transparency and acceptance of artificial intelligence (AI) and machine learning (ML) techniques in chemical risk assessment is the focus of this initiative. With an increasing reliance on these advanced methods for predicting chemical behaviour and assessing risks, addressing the challenges posed by unclear documentation and limited access to underlying data and algorithms is essential. This lack of transparency often hampers understanding and complicates the evaluation of uncertainties in these models.

The initiative will involve a thorough review and analysis of existing AI and ML-based and data-driven quantitative structure-activity relationship (QSAR) models ↗, aiming to identify best practices for transparency and regulatory applicability. By establishing clear reporting standards and decision-making criteria, the project will enhance the reliability and communication of uncertainties associated with these predictive models. Additionally, exemplary models will be curated and made available as FAIR (Findable, Accessible, Interoperable, and Reusable) data through the QsarDB.org repository ↗.

Ultimately, this effort seeks to foster better-informed decision-making for the protection of human health and the environment while reducing the need for animal testing, thereby contributing to a more effective regulatory framework in chemical risk assessment.

Achievements & Results

• Project group established with 10 participating partners, ensuring collaborative efforts.
• Definition of research priorities and requirements, aimed at focusing on the project objectives.
• A survey has been conducted on the use of ML and AI approaches.
• Review to gather information on ML new approach methodologies (NAMs) for has been completed for chemical hazard identification, providing also framework for assessing ML NAMs.
• Ongoing review to gather information on AI new approaches for chemical risk assessment, aiming to enhance understanding and application in regulatory contexts.
• Examples on interpretation of computational NAMs have been provided together with respective data publications.

Policy relevance

This project supports hazard identification broadly, as the computational models developed are not limited to a single regulatory framework. This flexibility is valuable, given that ML and AI-based QSAR approaches, also known as in silico or computational NAMs, are emerging as powerful tools across multiple regulatory domains. While conventional QSAR models are already applied in frameworks such as REACH, BPR, and CLP (ECHA), as well as in EFSA-regulated areas like pesticides, cosmetics, and pharmaceutical additives, newer ML/AI models require further validation to ensure regulatory applicability.

Aligned with the OECD QSAR Assessment Framework ↗ (QAF), which offers general guidance regardless of the modelling technique, this project addresses a key gap: the lack of clear guidance on how to evaluate and apply complex ML and AI models in regulatory contexts. By doing so, it contributes to making these next-generation tools more accessible and acceptable for chemical risk assessment and regulatory decision-making. While traditional QSAR models are better understood and already used in regulatory context, the application of complex ML and AI models is still an open challenge. This project aims to provide additional guidance on handling complex ML and AI QSAR approaches, that is today largely missing in regulatory settings.

Overview

New scientific methods, such as New Approach Methodologies (NAMs) ↗, generate a large amount of valuable data, but using this for regulatory and toxicological purposes remains a challenge without a clear and integrated framework. Adverse Outcome Pathways (AOPs) ↗ offer a promising solution. They are organised roadmaps that describe existing knowledge on how a chemical may cause harm – linking molecular initiating events that are triggered by chemicals - to biological changes and adverse health effects.

This project addresses current gaps by developing comprehensive AOPs ↗ for key regulatory concerns, including immune system toxicity ↗, neurotoxicity ↗, non-genetoxic carcinogenicity ↗, endocrine disruption ↗ and metabolic changes.

Teams of experts will identify existing AOPs, spot missing knowledge, and develop new AOPs using consistent, transparent methods.

The project will enhance tools, for examplebased on artificial intelligence, and methodologies for AOP construction. Four specialised teams have been established to identify potential biomarkers and develop corresponding AOPs that signal harmful effects.

By connecting mechanistic data with regulatory needs, this initiative will enhance how chemicals are assessed for safety. The outcomes will support the use of NAMs ↗ and integrated approaches (IATA ↗) in evaluating chemicals, plant protection products, biocides, cosmetics, and food-related substances. Ultimately, the project aims to contribute to safer products, informed policies and a healthier environment.

Policy relevance

AOPs provide a science-based framework that enhances the relevance and transparency of regulatory decisions by linking mechanistic data to adverse health outcomes.

Overview

This project focuses on current methods for managing chemical mixtures in various regulatory areas, such as REACH ↗, Classification, Labelling and Packaging (CLP ↗), pesticides, biocides, cosmetics, food contact materials, pharmaceuticals, and regulations concerning food, drinking water, and environmental emissions. Another objective is to evaluate the use of the Mixture Assessment Factor (MAF) approach for assessing and managing chemical mixtures beyond REACH, comparing it to other mixture assessment methods. MAF is a way to manage the risks of chemical mixtures. Instead of looking at each chemical separately, MAF sets a limit on the total amount of all chemicals in a mixture that can be considered safe.  

The project will explore whether MAF is applicable, under what conditions, and how different methods may lead to varying conclusions when tested with real-world data. Additionally, it will assess whether MAF could introduce biased results.

This initiative is crucial for improving the regulatory management of chemical mixtures, ensuring better protection of human health and the environment. It directly contributes to the project’s goal of developing regulatory and legally accepted risk assessment and management approaches for chemical mixtures.

By addressing these challenges, the project supports the development of more effective and harmonised regulation for chemical mixtures, improving safety measures across different areas of chemical legislation. 

Overview

Risk assessment traditionally focuses on single chemicals to identify potential adverse effects on human health. However, humans are exposed daily to many multiple chemicals. Evaluating the health risks of these chemical mixtures has become a priority.

The exposome approach adds value by studying the total external exposures over a lifetime and their links to health outcomes, providing insights into exposure-effect relationships.

The project builds on international scientific advancements in assessing the risks of chemical mixtures developed by leading international organisations such as the European Food Safety Authority (EFSA ↗), the European Environment Agency (EEA ↗), the European Chemicals Agency (ECHA ↗), the European Commission’s Joint Research Centre (JRC ↗), and OECD ↗ assessment methods, which analyse the potential harm of chemicals, with epidemiological studies that investigate patterns and causes of health effects in populations. This combination addresses needs identified by various organisations, including EU Member States, the European Commission’s health and environment departments (DG SANTE ↗ and DG Environment ↗), and aligns with goals outlined in the EU Chemical Strategy for Sustainability ↗.

The main goals of the project are to:

• Develop a unified strategy for assessing human health risks from chemical mixtures.
• Combine exposome data (lifetime exposure) with traditional risk assessment methods.
• Identify and prioritise real-life chemical mixtures using data from human biomonitoring.
• Generate detailed hazard and kinetic information for prioritised chemical mixtures.
• Investigate how chemical traces in the body relate to health effects.
• Conduct risk assessments for the prioritised mixtures to better understand their impact on human health.

Key messages

• The human relevance of testing strategies using toxicity studies in experimental animal studies and/or new approach methodologies (NAMs) is usually uncertain.
• A pragmatic workflow for human relevance assessment of adverse outcome pathways (AOPs) and NAMs would greatly help to overcome this challenge.
• By testing the workflow in two realistic case studies, we succeeded in making various improvements, both to the workflow itself as well as to the accompanying guidance and templates.

Overview

Understanding whether scientific evidence and test methods accurately reflect effects on human health is essential for reliable chemical safety assessments ↗; this is typically referred to as 'human relevance'. The project aims to improve how human relevance is evaluated. The workflow focuses on toxicological pathways, known as AOPs ↗, that describe the mechanisms via which a chemical can induce adverse health effects. The workflow encompasses a structured, step-by-step evaluation for assessing whether AOPs, and the test methods used to study them, are applicable to humans.

In collaboration with the European agencies EFSA ↗ and ECHA ↗, the project team tested the workflow using two case studies that represent different levels of expected human relevance. Based on the findings, the workflow and supporting materials were improved to enhance clarity, usability, and scientific consistency. This work contributes to better integration of non-animal testing methods ↗ in risk assessment and supports more human-relevant decision-making. 

Achievements & Results

Building on previous work ↗, the project delivered an improved version of the workflow for human relevance assessment of AOPs and NAMs, including updated guidance, structured templates, and a curated toolbox of supporting resources. Insights from two case studies led to clearer criteria for evaluating biological and empirical evidence, more consistent weight-of-evidence assessments, and better handling of context-specific factors such as age, sex, and tissue sensitivity. Input from (regulatory) scientists with different areas of expertise was instrumental to better align the workflow with practical needs, increasing its potential for future regulatory use. The refined workflow is now more user-friendly, adaptable, and better equipped to support modern, non-animal testing strategies in human health risk assessment. 

Policy relevance

The project supports European-wide goals to better utilize human-relevant scientific knowledge in chemical safety assessments and to reduce the use of experimental animals for toxicity testing. Developed with input from EFSA and ECHA, the workflow is aligned with current and near future regulatory needs and next-generation risk assessment approaches.

Overview

The European Chemicals Agency (ECHA ↗) is incorporating international guidelines like the revised OECD Guidance Document 150 ↗ into its regulatory processes for evaluating biocides ↗ and pesticides ↗ for potential endocrine-disrupting ↗ effects. However, current testing methods and regulations still fall short when it comes to identifying substances that interfere with the thyroid hormone system. These substances, known as thyroid hormone system disruptors, can impact the normal functioning of the thyroid, which is crucial for regulating metabolism, growth, and development.

Laboratory tests, called in vitro assays, can detect early molecular changes associated with thyroid hormone system disruptors, but they are still under validation for regulatory use.

Developing new approach methodologies (NAMs) would create the possibility to assess a wider range of effects caused by these disruptors, giving insights into the broader health impacts they may cause.

This project aims to understand how thyroid hormone system disruptors work at a molecular level. This way, more targeted testing methods that better detect these disruptors can be developed. The research will also improve methods for predicting how findings from lab models, such as rodent studies, actually apply to humans. To achieve this, the project will use computer modelling (in silico assays), human stem cell-based laboratory systems, and zebrafish. This approach will help refine how thyroid hormone disruptors are identified and assessed, ultimately contributing to better protect human health.

Overview

Developmental and adult neurotoxicity describe harmful effects on the developing or mature nervous system. They are currently assessed using specific studies and according to international guidelines ↗, such as those from the Organisation for Economic Co-operation and Development (OECD ↗). These guideline studies require significant resources, making them impractical for evaluating adverse effects of large numbers of chemicals. Because of this, there is an international agreement ↗ that testing for developmental neurotoxicity needs to be faster and more directly relevant to humans. To achieve this, experts are working to replace traditional methods with a group of new, more efficient tests designed for regulatory purposes.  

The current state-of-the-art involves a set of lab-based experiments called the Developmental Neurotoxicity in vitro test battery ↗ which use cells from humans and rats to study important processes in brain development. While this is a major step towards establishing an alternative testing regime, there are still gaps in the kinds of effects these tests can detect. The main goal of this project is to fill those gaps.  

To improve the current testing battery and create a system for testing effects on adult brains, this project will focus on three major tools: i) human cells, which avoid difference between species, (ii) zebrafish embryos, which are useful because they contain a complete nervous system capable of performing complex behaviours that could potentially be disrupted by chemical exposure, and (iii) computer-based methods that use models to predict neurotoxic effects.  

New Approach Methodologies (NAMs ↗) will look at areas that have not been fully explored before, such as:  

• How disruptions in hormone systems (endocrine disruption ↗), gene activity (transcriptomics), and long-term genetic regulation (epigenetics) affect brain development,  
• The formation and function of brain connections (synaptogenesis and neural networks),  
• The development of the blood-brain barrier (a protective layer in the brain),  
• Behavioural effects like reflex responses (startle), anxiety-like behaviour, and learning and memory.  

Achievements & Results

A joint paper ↗ identifies key research gaps that this project aims to address, providing a framework for advancing toxicological understanding. 

One study ↗ explored genes essential for brain development, including those involved in forming neural connections, maturing different types of brain cells, and responding to hormone-disrupting chemicals. 

In behavioral testing, researchers enhanced a zebrafish model by adding new ways to measure their reactions to light changes. This revealed how a chemical, PFOS, causes an exaggerated startle response, shedding light on how it affects behavior and brain function. Explore the findings here ↗.

Another publication distinguishes between testing methods for chemical safety from collecting data to developing comprehensive, reliable tests, emphasizing the importance of well-structured methodologies. Access the full publication here ↗.

Advances in testing strategies are reshaping developmental neurotoxicity research. A recent review highlights the growing use of innovative, animal-free testing methods to study the effects of chemicals on brain development. These approaches are driven by emerging technologies and international testing guidelines, such as those from the OECD. Learn more here ↗.

Finally, a new model using human-like brain cells, called LUHMES neurons, enables researchers to study nerve damage more effectively. This method allows detailed observation of nerve endings, measurement of specific markers, and analysis of biochemical changes after injury. See the full study here ↗.

Policy relevance

The EU's REACH ↗ regulations mandate comprehensive neurotoxicity testing for chemicals, but traditional methods are resource-intensive and impractical for evaluating large numbers of substances. This project seeks to create faster and more human-relevant testing methods for neurotoxicity, focusing on both developmental and adult effects. It emphasizes lab-based tests that address critical processes in brain development while working to close gaps in existing approaches. The ultimate aim is to recommend these improved methods for inclusion in regulatory testing frameworks.  

Overview

This project is focusing its research on developing new approach methodologies (NAMs ↗) to assess how chemicals effect the immune system. This addresses three key areas: organ-specific immune effects, particularly in the respiratory system and related allergic reactions; immune system suppression, measured through its response to vaccination; and improved models for studying how chemicals impact immune cells by identifying key biological processes involved.

The goal is to create innovative testing methods for these aspects of immune system effects.

To achieve this, well-understood reference chemicals will be used to develop and refine the methods. Once established, these methods will be tested on substances prioritised by the Partnership for the Assessment of Risks from Chemicals (PARC), where relevant. They will also contribute to the development of Adverse Outcome Pathways ↗, which link chemical exposure to harmful health effects, and integrated strategies for assessing chemical risk.

The results of this project will be relevant to improving chemical safety regulations across Europe.

Policy relevance

• REACH: several immune related outcomes are relevant for REACH such as skin sensitisation, respiratory sensitisation, immunosuppression. Currently under REACH, the immunotoxicity investigations are triggered based on repeated dose toxicity studies (28- or 90-day) in case there are some indications of immunotoxicity. If indications of immunosuppression are seen, one can include e.g. Cohort 3 into the study design of EOGRTS (developmental immunotoxicity) or request to have an immunotoxicity investigation included in a standard repeated dose toxicity study (adult immunotoxicity).
• CLP (Reg EC 1272/2008): While respiratory sensitisation is mentioned as a hazard in the CLP regulation, it is acknowledged that there is no respective method to detect respiratory sensitisers. Hence, a need to develop methods to detect respiratory sensitisers is recognized. On top of that, the CLP regulation foresees that non-animal testing is conducted wherever possible, implying support for the development of NAMS.
• Plant protection products (Reg EC 1107/2009) and biocides (Reg EC 528/2012): Sensitisation is analysed as part of the data requirements for plant protection products and biocides. The need to develop methods for respiratory sensitisation as well as alternative testing strategies is recognized.
• Cosmetic products: skin sensitisation.
• Food contact materials (Regulation (EC) No 1935/2004): allergenicity.
• Food contaminants (Regulation (EC) No 1881/2006) and enzymes (Regulation (EC) No 1332/2008): allergenicity.
• ECHA's KARC document ↗ (2023) stated the need for developmental immunotoxicity (DIT). NAMs developed and/or models characterized in this project could also feed the DIT needs.

Key messages

• As chemical safety testing moves away from traditional animal experiments and towards more human-relevant methods, called new approach methodologies (NAMs), the use of machine learning (ML) and other artificial intelligence (AI) tools are becoming more important.
• To use these AI/ML tools in real-world regulatory chemical safety decisions, regulators need to be confident that they are reliable and trustworthy.
• Formerly, in vitro NAMs were questioned with their trustworthiness/readiness for regulatory application. A readiness check and scoring system were developed to help assess NAMs readiness by a questionnaire.
• Inspired by the readiness checklist of the in vitro NAMs, READYAI project will develop a readiness check and scoring system for AI/ML-based tools used in.
• The goal is to give regulators a practical way to check how ready and reliable these AI tools are before using them in chemical safety assessment.

Overview

The rapid development of ML and other types of AI tools presents both opportunities and challenges for their integration into chemical risk assessment and regulation. While these computational tools offer promising applications in evidence management, toxicity prediction, and exposure assessment, their reliability for regulatory use remains unclear. READYAI project aims to fill this gap by establishing clear readiness criteria and a practical scoring system to evaluate the regulatory applicability of AI/ML tools.regulatory applicability of AI/ML tools.

The proposed system will be comparable to existing readiness frameworks for NAMs and will serve to guide regulatory scientists in determining the robustness and relevance of AI/ML-based tools.

A key component of the project is the development of a readiness check questionnaire designed specifically for AI/ML tools. This resource will be built in collaboration with AI developers, end-users, and relevant authorities to ensure its applicability across sectors and regulatory domains.

By supporting transparent and structured evaluation of AI/ML tools, the READYAI project contributes to more consistent and confident use of AI in chemical regulatory contexts. It aligns with PARC’s objectives of modernising risk assessment, reducing reliance on animal testing, and harmonising scientific approaches across the EU.

Achievements & Results

• The READYAI project officially kicked off in May 2025.
• Initial implementation steps are already underway.
• A steering committee is currently being assembled, including representatives from international and national agencies such as ECHA, EFSA, OECD and Swissmedic.
• The team has also started working on a concrete project plan to guide next steps.

Policy relevance

Chemical Risk Assessment is legally binding. So far, respective OECD-guided animal studies have been the basis of setting human health-based guidance values. With the paradigm change towards next generation risk assessment using NAMs, AI/ML-based tools move into the focus of regulatory agencies. Understanding these tools’ readiness and applicability will introduce a large change into policy.