PARC Projects

Shift away from animal testing
Rethinking genotoxicity testing: A non-animal approach
NGRA
Human health
Health effects
Time span
-
Potential impacts
  • Development of an Adverse Outcome Pathway (AOP)-based IATA for genotoxicity, featuring a comprehensive overview of applicable test methods and a partially quantitative AOP framework
  • Demonstration of IATA applicability through a series of case studies, initially with known (non-)genotoxicants and subsequently with more complex compounds in collaboration with regulatory agencies
  • Potential benefits for EU agencies involved in genotoxicity assessment and various regulations addressing this hazard class, fostering harmonisation of data requirements
Partners involved
INRAE (FR)
BPI (GR)
IRFMN (IT)
IRSN (FR)
ISS (IT)
KWR (NL)
LIST (LU)
MUI (AT)
NILU (NO)
NIPH (NO)
RIVM (NL)
STAMI (NO)
UG-PL (PL)
VUB (BE)
WR (NL)
WU-TOX (NL)
Contacts
Birgit Mertens (Sciensano)
birgit.mertens [at] sciensano.be
Marc Audebert (INRAE)
marc.audebert [at] inrae.fr
Overview

Ensuring chemicals safety for human health and the environment requires reliable testing methods. However, traditional genotoxicity assessments - used to determine whether a substance can damage DNA - often rely on animal testing and fail to incorporate modern scientific advancements.  

The project is leading the way in developing Integrated Approaches to Testing and Assessment (IATA ↗) for genotoxicity, creating a more effective, ethical, and science-driven framework for various health effects, with a primary focus on human health and some consideration for environmental health.

These approaches ensure collaboration with relevant stakeholders (ECHA ↗, EFSA ↗) and evaluate through targeted case studies. Genotoxicity stands out as an appropriate area for IATA development due to the wealth of existing data and available testing systems, such as 3D cell models, gene expression biomarkers, and advanced computational tools, to enhance the accuracy of risk assessments.  

Aligned with the EU Chemicals Strategy for Sustainability ↗, this project aims to establish a robust, standardised approach to evaluating genotoxicity while reducing reliance on animal testing. The project is also exploring how these innovative methods can be seamlessly integrated into regulatory decision-making, ensuring safer chemicals for both people and the planet. 

Achievements & Results
  • An AOP network leading to permanent DNA damage has been drafted and presented and discussed at several international meetings and events.
  • Database with data from NAMs ↗ in TK6 cells for alkylating compounds (EMS, MMS and ENU) has been created to support the AOP ↗ development.
  • Drivers of variability in traditional genotoxicity tests have been identified. 
Policy relevance

Discussions with regulators (EFSA, ECHA and JRC ↗) have started to formulate the regulatory problems that need to be addressed with our IATA. The outcomes of these discussions have been taken up in the two proposed case studies (i.e. one related to classification and labelling and one related to the genotoxicity assessment of food contaminants). Moreover, experts from ECHA and EFSA are involved in the case study subgroup meetings and/or project meetings. 

Related Projects

Harmonised workflow for human relevance assessment of Adverse Outcome Pathways (AOPs) and New Approach Methodologies (NAMs)
Advancing endocrine disruptor assessment
New approaches to assess organ toxicity without animal testing
Filter by
Address chemical pollution in the natural environment
Provide protection against most harmful chemicals
Shift away from animal testing
Biodiversity protection
Developing a system to monitor chemicals in the environment
Enhancing data integration and risk assessment for chemical exposure
Environmental and multisource monitoring: Pilot study on PFAS and endocrine disruptors
Improving the environmental risk assessment for plant protection products
Innovative tools for an early warning system
Monitoring chemicals in wastewater using innovative techniques
Tracking emerging chemicals in animal species: A new monitoring approach
Understanding volatile siloxanes in Europe to support regulation
Advancing the characterisation of human chemical exposome with innovative methods
Advancing tools, knowledge and regulatory options for an improved risk assessment and management of chemical mixtures
Beyond food: Organic contaminants in daily environments
Enhancing the reusability of human biomonitoring data for improved health risk assessment
Establishment of advanced data processing methodologies and bioinformatic tools for a non-targeted screening repository
Harmonising quality of chemical and bio-effect directed suspect and non-target screening methods across fields
Health-based guideline values for indoor air
Leveraging HBM4EU data for chemical safety and zero pollution in Europe
Streamlining data processing methods for suspect and non-target screening
Testing assessment tools for hazardous substances in consumer products and articles
Toxicity of plastic-associated chemicals
Advancing detection mechanisms of hazardous chemicals in food
Assessing chemicals exposure of waste management workers
Boosting data availability for environmental burden of disease calculations of chemicals
Developing and testing new approaches for chemical exposure assessment of infants
Developing a sustainable European human biomonitoring framework
Developing indicators for chemical risk and health impact assessment
Enhancing healthy and safe working conditions in hospitals
Establishing health-based human biomonitoring guidance values
Hazard characterisation of emerging mycotoxins
Human biomonitoring studies on the general population
Implementing human biomonitoring as sentinel surveillance system
Improving chemical screening in human samples
Investigating mono-n-hexyl phthalate (MnHexP) exposure
More accurate health impact assessment methodologies for chemicals
Occupational biomonitoring of emerging chemicals: A new approach
PFAS in breast milk and infant health
Roadmap linking chemical substances and health
Tracking human exposure to environmental pollutants over time in Europe
Tracking PFAS exposure in children across Europe
Using case studies to assess health impact of exposure to chemical substances
Using general population human biomonitoring data to trace occupational exposure
Assessing the relevance of adverse outcome pathways (AOPs) and associated new approach methodologies (NAMs) for human health risk assessment
Demonstrating the applicability of New Approach Methodologies for regulatory use
Harmonisation of the risk assessment of chemicals
Improving regulatory readiness of new testing methods
Innovative testing strategies for the developing immune system
In vitro methods to assess respiratory uptake and toxicity
New tools for enforcing chemical safety in everyday items
New tools to assess fish thyroid disruption
Omics for chemical grouping and read-across
Sex-based differences in susceptibility to liver toxicants
Skin sensitisation and mixtures effects
Tools, criteria and methods for risk assessment
Towards a harmonised approach in chemical risk assessment
Understanding how chemicals can disrupt hormones and reproductive health
Advanced tools to identify metabolism-disrupting chemicals
Advancing endocrine disruptor assessment
Assessing unknown mixtures using monitoring data and new approach methods
Better tools to spot hidden cancer risks
Computational new approach methods based on machine learning and artificial intelligence
Developing toxicity roadmaps
Enhancing chemical mixture risk assessment and regulation
Enhancing the risk assessment of chemical mixtures
Harmonised workflow for human relevance assessment of Adverse Outcome Pathways (AOPs) and New Approach Methodologies (NAMs)
Improving testing methods for thyroid hormone disrupting chemicals
Innovative approaches to assess developmental and adult neurotoxicity 
Innovative testing of chemical effects on the immune system
READYAI: Setting clear rules to assess when Artificial Intelligence can be trusted and used for evaluating chemical safety
Rethinking genotoxicity testing: A non-animal approach
Trusting new ways to test chemicals – the importance of retrospective validation
Advancing chemical risk assessment for diverse populations
Alternative predictive toxicology integrative approaches for chemical safety
Closing data gaps in physiologically-based kinetic modeling and quantitative in vitro to in vivo extrapolation
From emission to impact: modelling chemical pathways to human exposure
Integrating occupational and general exposure assessment
New approaches to assess organ toxicity without animal testing
New directions in systems toxicology for chemical safety
Advancing safe pesticide use through landscape risk assessment
Assessing the effects of naturally occurring toxins on aquatic ecosystems
Benchmarking the environmental risk assessment of plant protection products
Improving chemical risk assessment with new approach methods
Improving environmental risk assessments for plant protection products
Testing less complex pesticide risk assessment models for environmental regulation
Understanding risks from BPA alternatives on the environment
Environment
Health effects
Human health
Monitoring methods
Risk assessment
NGRA
Mixtures
Human biomonitoring
Workers
Streamlining data processing methods for suspect and non-target screening
Streamlining data processing methods for suspect and non-target screening

Rethinking genotoxicity testing: A non-animal approach

Time span
-
Potential impacts
  • Development of an Adverse Outcome Pathway (AOP)-based IATA for genotoxicity, featuring a comprehensive overview of applicable test methods and a partially quantitative AOP framework
  • Demonstration of IATA applicability through a series of case studies, initially with known (non-)genotoxicants and subsequently with more complex compounds in collaboration with regulatory agencies
  • Potential benefits for EU agencies involved in genotoxicity assessment and various regulations addressing this hazard class, fostering harmonisation of data requirements
INRAE (FR)
BPI (GR)
IRFMN (IT)
IRSN (FR)
ISS (IT)
KWR (NL)
LIST (LU)
MUI (AT)
NILU (NO)
NIPH (NO)
RIVM (NL)
STAMI (NO)
UG-PL (PL)
VUB (BE)
WR (NL)
WU-TOX (NL)
Overview

Ensuring chemicals safety for human health and the environment requires reliable testing methods. However, traditional genotoxicity assessments - used to determine whether a substance can damage DNA - often rely on animal testing and fail to incorporate modern scientific advancements.  

The project is leading the way in developing Integrated Approaches to Testing and Assessment (IATA ↗) for genotoxicity, creating a more effective, ethical, and science-driven framework for various health effects, with a primary focus on human health and some consideration for environmental health.

These approaches ensure collaboration with relevant stakeholders (ECHA ↗, EFSA ↗) and evaluate through targeted case studies. Genotoxicity stands out as an appropriate area for IATA development due to the wealth of existing data and available testing systems, such as 3D cell models, gene expression biomarkers, and advanced computational tools, to enhance the accuracy of risk assessments.  

Aligned with the EU Chemicals Strategy for Sustainability ↗, this project aims to establish a robust, standardised approach to evaluating genotoxicity while reducing reliance on animal testing. The project is also exploring how these innovative methods can be seamlessly integrated into regulatory decision-making, ensuring safer chemicals for both people and the planet. 

Achievements & Results
  • An AOP network leading to permanent DNA damage has been drafted and presented and discussed at several international meetings and events.
  • Database with data from NAMs ↗ in TK6 cells for alkylating compounds (EMS, MMS and ENU) has been created to support the AOP ↗ development.
  • Drivers of variability in traditional genotoxicity tests have been identified. 
Policy relevance

Discussions with regulators (EFSA, ECHA and JRC ↗) have started to formulate the regulatory problems that need to be addressed with our IATA. The outcomes of these discussions have been taken up in the two proposed case studies (i.e. one related to classification and labelling and one related to the genotoxicity assessment of food contaminants). Moreover, experts from ECHA and EFSA are involved in the case study subgroup meetings and/or project meetings. 

Contacts
Birgit Mertens (Sciensano)
birgit.mertens [at] sciensano.be
Marc Audebert (INRAE)
marc.audebert [at] inrae.fr
Topics
Shift away from animal testing
Keywords
NGRA
Human health
Health effects

Related Projects

Harmonised workflow for human relevance assessment of Adverse Outcome Pathways (AOPs) and New Approach Methodologies (NAMs)
Advancing endocrine disruptor assessment
New approaches to assess organ toxicity without animal testing