Key messages

This project aims to assist Member State regulatory authorities, EU agencies, scientific committees, expert groups, relevant Commission departments and the industry in adopting harmonised risk assessment methodologies on selected human health effects:

• Contribute to a harmonised way of using existing and emerging New Approach Methodologies (NAMs ↗) for risk assessment of compounds with potential endocrine-disrupting (ED) concerns.
• Remove current bottlenecks regarding acceptance of non-validated in vitro ED test methods; provide confidence in risk assessors and consistency in the assessment of data from non-validated ED test methods for use in WoE assessment.
• Contribute to the harmonised implementation of the new CLP criteria on hazard classes for endocrine disruption taking into consideration all available methods and tools.
• Contribute to the development of harmonised risk assessment methodology on skin sensitisation.
• Identify the most relevant gaps and inconsistencies in current legislation for genotoxicity and carcinogenicity risk assessment, highlighting potential of improvement and harmonisation.
• Support the integration of information from different sources (e.g. NAMs, AOPs ↗) identifying their best placement into genotoxicity and carcinogenicity risk assessment detailing and addressing the underlying uncertainties.  
• Identify areas where further development of legislation or regulatory practice is needed regarding the performance of DNT studies highlighting potential of improvement and harmonisation to ensure a high level of protection for human health. 

Overview

Chemical risk assessments in the European Union (EU) are carried out under different regulatory frameworks, leading to inconsistencies in methodology and results. The call for innovation in risk assessment to ensure more effective and harmonised assessments across sectors through the European Green Deal ↗ and the Chemicals Strategy for Sustainability ↗ call for innovation in risk assessment to ensure more effective and harmonised assessments across sectors through the 'One substance, one assessment' approach.

This project will review risk assessment methodologies for key health endpoints prioritised in the EU Chemicals Strategy, including endocrine disruption ↗, skin sensitisation ↗, genotoxicity ↗, carcinogenicity ↗ and developmental neurotoxicity ↗. Case studies will analyse current regulatory practices under different EU legislations to identify opportunities for harmonisation and improved methodologies.

For example, endocrine disruptors are currently assessed using different approaches despite a common WHO/IPCS definition ↗, leading to inconsistencies in data requirements and outcomes. The introduction of new hazard classes for classification and labelling of chemicals with endocrine disrupting properties aims to improve regulatory alignment. Similarly, skin sensitisation, a chronic immune response caused by chemical exposure, requires standardised assessment to ensure public health protection.

Current non-animal genotoxicity and carcinogenicity tests may fall short of fully capturing the complexities of human health risks. This project pioneers advancements in these methods aiming for optimising regulatory acceptance while ensuring the highest level of human health protection.

In addition, the assessment of developmental neurotoxicity varies between regulatory frameworks, requiring greater consistency in study design and interpretation.

By bridging methodological gaps and aligning regulatory processes, this project will support more transparent and efficient science-based approaches to chemical risk assessment, ultimately improving health and environmental protection across the EU. 

Achievements & Results

• An analysis is ongoing on risk assessment of cosmetic ingredients according to both current methodology by the Scientific Committee on Consumer Safety and the new Next Generation Risk Assessment methodology. High priority cosmetic ingredients for which concerns for endocrine disruption exist (list A) have been identified and are used in this context: Genistein, Benzophenone-4 and Octocrylene.  
• Criteria are developed by Benaki Phytopathological Institute (Greece) for the assessment of reliability and relevance of scientific literature data with focus on in vitro transactivation assays, so that research published work is more consistently used in chemical risk assessments and regulatory decision making. The scientific criteria will be embeded in a user friendly, publicly available on line platform, the SciRAP tool ↗ supported by the Karolinska Institute, Sweden.
• Classification of chemicals for endocrine disrupting properties is an EU legal requirement and there is an urgent need to facilitate the assessment of endocrine disruptors with State-of–Science methods. Several research institutes and regulatory bodies across Europe have joined forces and published ↗ a 2024 inventory of in silico, in vitro and in vivo test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment. Further work on disruption of the estrogen, androgen and steroidogenesis pathways from chemicals is ongoing.
• As risk assessment of skin sensitising chemicals is required under different EU Regulations (Classification Labelling and Packaging, REACH ↗, Cosmetic Products and Detergents, Biocidal products, plant protection products and toys regulation) questionnaires to national authorities and EU bodies on mapping of current practises has been completed. Approximately 40% of the questionnaire respondents found that the EU legislation and tools were not sufficiently protective. To improve the legislation 83% suggested harmonisation and 68% suggested better data sharing. Other areas were: improved exposure data (78%), better understanding of the skin sensitization mechanism (67%) and non-animal tests (66%).
• Risk assessment strategies on genotoxicity and carcinogenicity have been mapped and compared focusing on evaluation of the usage of computational predictive toxicology tools such as Quantitative Structure-Activity Relationships (QSAR). According to work conducted by the Istituto Superiore di Sanità in Italy, the OECD QSAR Assessment Framework ↗ has been identified as a suitable tool for evaluating the models and their predictions.
• Developmental neurotoxicity assessments are often hindered by study and data availability as highlighted by scientists in Stokholm University and this has been the basis of a suggestion on Sustainable Use of plant protection product Regulation (SUR), Amendment 663 ↗. Extraction of raw data for motor activity is finalised, and the extraction of metadata and ancillary data is ongoing. Focus is given to support the intuitive identification of (i) extreme values potentially reflecting sensitive subpopulations; (ii) cases where data variability increases with dose, and (iii) cases where motor activity habituation is affected across ages and/or sexes. 

Policy relevance

The outcome of this project will be relevant to the implementation of the following EU Legislation:

• Cosmetic Products Regulation (Regulation (EC) No 1223/2009) - [CS9, CS10, CS11, CS17, CS18].
• REACH Regulation (Regulation (EC) No 1907/2006) - [CS9, CS10, CS11, CS15, CS17, CS18].
• CLP Regulation (Regulation (EC) No 1272/2008) - [CS9, CS10, CS11, CS17, CS18].
• Detergents Regulation (Regulation (EC) No 648/2004) - [CS9].
• Biocidal Products Regulation (Regulation (EU) No 528/2012) - [CS9, CS15, CS17, CS18].
• Toys Directive (Directive 2009/48/EC) – [CS9].
• Medical Devices Regulation (Regulation (EU) 2017/745) - [CS9].
• Plant Protection Products Regulation (Regulation (EC) 1107/2009) - [CS9, CS11, CS15, CS17, CS18].
• Data requirements for active substances Regulation (Regulation (EU) No 283/2013) - [CS9, CS15].
• Inspection and verification of GLP Directive (Directive 2004/9/EC) – [CS15].
• GLP and applications for tests on chemical substances Directive (Directive 2004/10/EC) – [CS15].