Scientific Opinion
Negotiated procedure
Methodology
Methodologies guide scientists through the scientific process by providing a step-by-step framework for:
What to answer – describing the precise nature of the scientific question and what is outside of scope. Scientists often refer to this as the “problem formulation”.
Which evidence to collect and use
- identifying the scientific evidence relevant for an assessment
- if needed, complementing evidence from observations (e.g. studies on animals or cells) with other sources or methods (e.g. expert knowledge)
- evaluating quality of scientific evidence and analysing it in a structured, consistent and traceable way
- document the process for dealing with evidence transparently.
How to make decisions – providing a transparent, rational and accountable process for scientific decisions so that the process can be repeated by other scientists.
Innovative Risk Assessment Methodologies Programme (IRMA)
In 2022 EFSA established the Innovative Risk Assessment A specialised field of applied science that involves reviewing scientific data and studies in order to evaluate risks associated with certain hazards. It involves four steps: hazard identification, hazard characterisation, exposure assessment and risk characterisation Methodologies (IRMA) Programme to ensure preparedness and knowledge of up-to-date risk assessment methodological developments. The programme also aims to meet new scientific challenges that EFSA is called to face in the coming five years in food, feed, and environmental safety assessment.
IRMA guarantees consistent and updated methodologies, prepares for new assessment needs driven by scientific and legislative changes, and enables rapid response to emerging risks and crises, enhancing the efficiency and reliability of EFSA's scientific advice.
Among the wide range of projects under the IRMA umbrella, below we highlight those of specific interest to our stakeholders:
Projects under the IRMA Programme
Risk Assessment is increasingly generating information using new approach methodologies (NAMs) as alternatives to animal testing. Yet, chemical risk assessments are still based mainly on toxicological data using animal models and many efforts are ongoing at EFSA, and other European and International agencies to integrate such NAMs in next generation risk assessment. In addition, European Commission services will publish a road map for the phasing out of animal studies, requested by over 1.2 million citizens to the European parliament, to further support these efforts and provide practical short-, mid- and long-term solutions.
Objectives: Develop in silico Research theoretical method, particularly involving computer models, to predict the likely toxicological, or other, effects of substances models and an open access platform: TKPlate to support the integration of NAMs in next generation risk assessment of chemicals for human, animal health and environmental risk assessment with a focus on toxicokinetic (TK) and toxicodynamic (TD) models.
Methodology: The project focuses on the development of TK and TD models for human populations, test species A subdivision of the genus, a species is a group of closely related and similar-looking organisms; for example, in the case of Homo sapiens (humans), the second part of the name (sapiens) represents the species and farm animals and their integration in the TKPlate platform. These include physiologically based kinetic models in humans, test species and farm animals, TD models for benchmark dose The minimum dose of a substance that produces a clear, low level health risk, usually in the range of a 1-10% change in a specific toxic effect such as cancer induction modelling, dynamic energy budget models for species in the environment and other more complex models investigating mixture toxicity and impact of multiple stressors on humans and animal species.
When setting health-based guidance values (HBGVs) uncertainty Scientific concept used in risk assessment to describe all types of limitations in available knowledge at the time an assessment is conducted, with the agreed resources, that affect the probability of possible outcomes to the assessment factors are applied to extrapolate animal data to humans and to consider inter-human variability. Yet, little is known about toxicodynamic variability in humans, and it is unclear if the uncertainty factors are sufficiently protective.
Objectives: Improve chemical risk assessment and refine HBGVs by addressing human variability in toxicodynamics (TD), more specifically understanding how differences in how individuals respond to toxic substances at cellular level, particularly in terms of cell stress and cell death pathways.
Methodology: The project addresses human variability in TD by generating cellular and transcriptional response data following the activation of specific stress and cell death pathways. An in vitro Research method which involves testing cells or tissues extracted from living organisms cell model of human peripheral blood lymphocytes is used as a source of freshly isolated cells from 150 individuals. Bayesian statistics is applied to model inter-individual differences.
Developmental neurotoxicity Any adverse effect on the nervous system (e.g. paralysis or loss of function) that results from exposure to potentially toxic substances (DNT) is a serious public health concern and better knowledge of risk factors is crucial to minimise new cases of neurodevelopmental disorders and cognitive deficits. Several studies indicate that to explain current incidence The number of new events occurring within a specified time period within a defined geographical area; for example, the number of flu cases per year in Europe of brain disabilities in humans, exposure to chemicals must be considered. Current DNT in vitro testing battery has gaps in coverage of neurodevelopment processes and cell types.
Objectives: Enhance the understanding of how chemical exposures affect brain health and development, focusing particularly on glial cells. The project develops and implements New Approach Methodologies (NAMs) to assess the toxicity of food toxicants on glial cell development and function, addressing existing gaps in developmental neurotoxicity testing.
Methodology: The project employs an integrative approach that combines transcriptomics One of the family of so-called 'omics methods: an approach to the study of gene expression whereby thousands of RNA molecules in a given sample (of tissue or cells) are analysed simultaneously. , in vitro assays, and Adverse Outcome Pathway A method of visualising a chain of events linked by causality that may lead to a harmful outcome for organisms or the environment (AOP) development. It involves the creation of novel in vitro models to predict glial-specific toxicological events, the expansion of existing AOP networks to incorporate glial-related key events, and the use of transcriptomics to generate and analyse relevant datasets. The findings will contribute to refining risk assessment frameworks and regulatory guidelines on DNT.
The lack of specific data requirements for pesticides residues, i.e. metabolites, in crops and/or animal products, e.g. milk, limits the harmonisation of risk assessment which has to be carried out on a case-by-case basis.
Objectives: Integrate New Approach Methodologies (NAMs) into the risk assessment of pesticide metabolites. The project is developing semi-automated and standardised workflows to improve the efficiency, transparency and harmonisation of pesticide metabolite Substance formed as a consequence of metabolism in an organism assessments, reducing reliance on traditional testing methods.
Methodology: The project involves the creation of a semi-automated workflow for mutagenicity The capacity to cause permanent, typically negative, changes to an organism and any offspring by altering the structure of its DNA assessment using the OECD QSAR Toolbox. Case-studies are conducted to demonstrate the practical implementation of these workflows, overall contributing to regulatory guidance on pesticide metabolite risk assessment.
The EU Green Deal aims at reducing the risk associated with pesticides use and reversing biodiversity A term used to describe the variety of living organisms existing in a specific environment loss. The development of risk assessment methodologies for non-target organisms could contribute to such ambitions.
Objectives: Advance Environmental Risk Assessment (ERA) The process of assessing potential harm to the environment caused by a substance, activity or natural occurrence. This may include the introduction of GM plants, the use of pesticides, or the spread of plant pests of plant protection products (pesticides) by integrating landscape and ecological features into risk assessment methodologies. The project addresses knowledge gaps in terrestrial ecotoxicology The study of the adverse impacts of substances, particularly chemicals, in relation to the environment and public health and enhances the assessment of non-target organisms in agro-ecosystems.
Methodology: The project involves the collection and generation of data to improve exposure and sensitivity assessments of non-target organisms. It also focuses on the identification of tools, such as population Community of humans, animals or plants from the same species models, to assess effects at higher biological levels. Additionally, the feasibility of developing an interoperable environment for risk assessment is explored. The findings will support the revision and development of guidance documents to enhance ERA methodologies.
Historical Control Data (HCD) are data from studies conducted under the same or similar conditions as the toxicity study under assessment. Their primary use is to support the interpretation of (possible) treatment-related effects in the toxicity study. However, there is no harmonised approach on the collection, evaluation and use of HCD.
Objectives: Elucidate the requirements for the use of HCD to better interpret toxicity studies used for regulatory purposes; clarify how HCD should be compiled as part of the regulatory dossier; and assist the interpretation of HCD in the context of the evaluation of regulatory studies.
Methodology: Information from the scientific literature, publicly available databases and stakeholder experience (survey, workshop and technical hearings) have been used. The EFSA Panel on Plant Protection Products and their Residues (PPR) developed a quantitative approach for the collation, evaluation and use of HCDusing a decision scheme which includes seven distinct steps grouped in three overall clusters of activity: planning, evaluation of the HCD, and use of HCD. In addition, illustrative case studies are available to elucidate the proposed methodology and templates offered to improve harmonisation for data submission.
European law requires that no active substance can be authorised if it causes endocrine disruption i.e. has an adverse effect A change in the health, growth, behaviour or development of an organism that impairs its ability to develop or survive on endocrine activity. To support this requirement, it is necessary to better understand the endocrine disrupting mode of action A sequence of events, identified by research, which explains an observed effect of active substances.
Objectives: Develop Adverse Outcome Pathways (AOPs) for the identification of substances with endocrine-disrupting properties, addressing regulatory challenges during the assessment of endocrine activity, particularly within the estrogenic, androgenic, thyroidal, and steroidogenic modalities.
Methodology: A top-down approach is used to construct AOPs, identifying key molecular initiating events and key events linked to endocrine disruption. Collaboration with the European Chemicals Agency (ECHA) and the Joint Research Centre (JRC) ensures harmonisation with existing frameworks. The developed AOPs will be submitted to the OECD AOP Wiki for broader regulatory adoption.
Some pesticides may have the potential to disrupt brain development. It is crucial to assess developmental neurotoxicity of chemical substances and to accelerate the development of in vitro methods to test the impact of chemicals on nervous system development.
Objectives: Improve the assessment of environmental neurotoxicants by developing an integrated in vitro neurotoxicity testing strategy, advancing hazard identification The first step in risk assessment, this involves the identification of biological, chemical, and physical agents capable of causing adverse health effects for developmental neurotoxicity (DNT) and other forms of neurotoxicity associated with chemical exposures, particularly pesticides.
Methodology: The project involves the development of a comprehensive DNT testing battery, incorporating in vitro assays and computational modelling to complement or replace in vivo Research method which involves testing individual live animals or populations of live animals testing. Data generated from these assays is analysed to refine assessment frameworks, with guidance documents developed to support regulatory implementation. Collaboration with the OECD, the Danish Environmental Protection Agency, and the US Environmental Protection Agency ensures alignment with international best practices.
New Approach Methodologies (NAMs) are considered promising for the assessment of nanomaterials, reducing the use of animal testing. Nanotechnology is a cross-cutting area impacting novel foods, feed additives, and food contact materials.
Objectives: Develop recommendations on the use of NAMs for nanomaterials and nanoparticles risk assessment in food and feed, and foster NAMs’ implementation within EFSA’s regulatory evaluations. The goal is to provide guidance and case studies to support EFSA Panels and applicants in adopting these innovative methodologies, minimising animal testing while moving towards mechanistic-based risk assessment.
Methodology: The project identifies relevant data sources, establishes protocols, generates data and develops tools for integrating NAMs into risk assessments. The development of a qualification system for NAMs and NAM-based integrated approaches to testing and assessment case studies demonstrate the practical applications. Engagement with stakeholders and other scientific advisory bodies ensures alignment with international developments and regulatory relevance. Lastly, initial provisions for guidance on NAMs data integration and implementing hypothesis-driven Next Generation Risk Assessment is being developed, with specific focus on the area of food and feed nanotechnology.
There is resistance among some scientists towards the use of in vitro New Approach Methodology (NAM) test systems because of doubts about their representation of human physiology, absence of a consensus framework for interpreting toxicogenomics data, and the need for advanced bioinformatics An umbrella term for biological studies that use computer programming as part of their methodology. Bioinformatics combines computer science, statistics, mathematics and engineering to study and process biological data. See also Transcriptomics, Proteomics and Metabolomics tools for hazard characterisation The second step in risk assessment, this involves defining the nature of the adverse health effects associated with biological, chemical and physical agents which may be present in food. The process should, if possible, involve an understanding of the doses involved and related responses.
Objectives: Advance chemical safety assessment by incorporating toxicogenomics and mechanism-based risk evaluation to develop a methodology for interpreting transcriptomics data, establish a quantitative framework and integrate bioinformatics for mapping Adverse Outcome Pathways.
Methodology: The project combines computational modelling, bioinformatics, and toxicogenomics to enhance risk assessment. It develops algorithms for transcriptomics interpretation, designs a prototype toxicogenomics tool, and aligns methodologies with international standards.
The project addresses the increasing complexity of novel food Foodstuff or food ingredient that was not used for human consumption to a significant degree within the European Union before 15 May 1997/feed products containing protein and the need to modernise protein safety assessment which is currently based on Codex Alimentarius guidelines published in 2003-2009.
Objective: Clarify and advance protein safety assessment making use of experience gained and new scientific advances achieved over the last 20 years. Through the review of trends and the exploration of new strategies, it aims to develop new approaches for protein safety assessments.
Methodology: The main activities are outsourcing and a workshop to communicate findings and gather feedback. This involves developing new approaches for allergenicity The ability to trigger an abnormal immune response that leads to an allergic reaction in a person assessment and in silico protein toxicity prediction software. The project is engaging with Codex Alimentarius and aims to revise current risk assessment strategies for open reading frames analysis.
Although not the focus of its risk assessment, EFSA’s 2015 scientific opinion Opinions include risk assessments on general scientific issues, evaluations of an application for the authorisation of a product, substance or claim, or an evaluation of a risk assessment includes an overview of data and literature summarising how the choice of ingredients, the storage method and the temperature at which food is cooked can influence the amount of acrylamide in different food types and, therefore, the level of dietary exposure For the purposes of risk assessment, measurement of the amount of a substance consumed by a person or animal in their diet that is intentionally added or unintentionally present (e.g. a nutrient, additive or pesticide).
Although not the focus of its risk assessment, EFSA’s 2015 scientific opinion includes an overview of data and literature summarising how the choice of ingredients, the storage method and the temperature at which food is cooked can influence the amount of acrylamide in different food types and, therefore, the level of dietary exposure.