How can chemical safety assessment account for biological complexity—from molecular pathways to organism-level outcomes—while also capturing diverse responses within and between species? ASPIS will bring this question to EUROTOX 2026, held in Vienna from 13 to 16 September.
On 15 September, ASPIS researchers and regulatory experts will demonstrate how New Approach Methodologies (NAMs) can capture biological complexity and diversity, using developmental neurotoxicity as a case study.
Celebrating the 60th edition of the EUROTOX congress series under the theme “Toxicology without borders”, EUROTOX 2026 will bring together scientists from academia, industry and regulatory bodies to exchange the latest advances in toxicology and strengthen international collaboration.
For ASPIS, participation comes at an important moment. Following the final ASPIS Open Symposium in Maastricht, the EUROTOX session provides a prominent platform to bring the cluster’s scientific results, regulatory dialogue, and collaborative legacy to the wider European toxicology community. It will draw together expertise from ONTOX, RISK-HUNT3R and the Organisation for Economic Co-operation and Development (OECD), connecting method development with practical pathways towards regulatory uptake.
SESSION AT A GLANCE
The title of the session: Crossing levels of biological complexity and diversity with new approach methodologies: developmental neurotoxicity as a case study
When: Tuesday, 15 September 2026, 16:30–18:00
Where: Hall M, Austria Center Vienna
Chairs: Mathieu Vinken (Vrije Universiteit Brussel), ASPIS coordinator for 2024–2026, and Bob van de Water (Leiden University), past ASPIS coordinator (2021–2022)
Speakers:
- Eliska Kuchovska (Leibniz Research Institute for Environmental Medicine)
- Marcel Leist (University of Konstanz)
- Magdalini Sachana (Organisation for Economic Co-operation and Development)
From mechanistic insight to regulatory confidence
Chemical safety evaluation is undergoing a fundamental shift: away from relying primarily on apical findings in animal studies and towards mechanistic, human-relevant approaches. New Approach Methodologies (NAMs) are central to putting Next Generation Risk Assessment (NGRA) into practice. NAMs are conceptually anchored in adverse outcome pathway networks (AOPs), which span over various stages of biological organisation ranging from the molecular all up to the organism level. By doing so, NAMs not only enable in-depth mechanistic investigation, but also allow to identify variations in biological responses to and outcome of toxic chemicals within and between species.
The EUROTOX session will examine this capacity using developmental neurotoxicity—the potential of chemicals to disrupt the developing nervous system—as a case study. Across three complementary presentations, the session will cover the characterisation of developmental neurotoxicity NAMs, their integration into NGRA, and OECD activities supporting their regulatory application.
Extending the ASPIS legacy
The session also reflects ASPIS's broader contribution to the transition towards animal-free, human-relevant chemical safety assessment. In their recent reflections on the cluster's legacy, the two session chairs highlighted this progression.
Mathieu Vinken described that
“ASPIS has demonstrated that NAMs can move from conceptual promise to regulatory-relevant solutions [...] and strengthened the scientific backbone needed to reduce and ultimately replace animal testing.”
Bob van de Water emphasised that
“ASPIS can create full workflows for Next Generation Risk Assessment that are completely based on animal-free testing.”
Researchers, regulators, and other toxicology professionals attending EUROTOX 2026 are warmly invited to join the session and contribute to the discussion on how NAMs can capture biological complexity and diversity while delivering evidence fit for future decision-making.
Session abstracts
Characterisation blueprint of DNT NAMs reflecting mechanistic complexity and model
— Eliska Kuchovska (Leibniz Research Institute for Environmental Medicine, Germany; ONTOX)
This presentation introduces developmental neurotoxicity (DNT) and the DNT in vitro battery (DNT-IVB) as a primer for the session, with the Neurosphere Assay (an integral component of the DNT-IVB) based on primary human neural progenitor cells (hNPCs) as the central reference model modeling key neurodevelopmental processes (KNDPs; e.g., proliferation, migration, neurite outgrowth, and differentiation). Previous studies on DNT IVB showed a high sensitivity of the oligodendrocyte differentiation and NPC proliferation KNDPs, warranting the inclusion of additional DNT NAMs—human-induced pluripotent stem cell (hiPSC)-derived NPCs (hiNPCs) and hiPSC-derived oligodendrocytes (hiOLs)—to examine these processes in greater depth.
A multi-layer characterisation of the selected models will be presented. First, a neurodevelopmental signaling- and hormonal receptor-anchored biological applicability domain links assay endpoints to the regulatory architecture of KNDPs, making explicit what each assay can and cannot assess. Second, exposure-responsive epigenomic profiling across developmental states supplies a mechanistic and temporal context; illustrative examples include retinoic-acid–modulated proliferation in hiNPCs and flame-retardant TDCIPP-associated effects during hiOL differentiation. Third, quantitative proteo-lipid measurements provide inputs for cellular partitioning to estimate the biologically effective dose (operationalised as intracellular free concentration) and to predict chemical behaviour within the DNT in vitro system, thereby supporting QIVIVE from nominal concentrations.
Together, these layers document scope, assumptions, and uncertainty across the Neurosphere Assay and complementary NAMs, improving interpretability and fitness-for-purpose assessment within adverse outcome pathway-informed risk assessment. By clarifying the applicability domain and quantitative translation steps, the characterisation offers a transparent basis that can support confidence in regulatory application.
Strategies for uncertainty reduction in DNT risk assessment within a multi-pronged risk assessment strategy
— Marcel Leist (University of Konstanz, Center for Alternatives to Animal testing, Germany; RISK-HUNT3R)
Next generation risk assessment (NGRA) strategies use animal-free New Approach Methodologies (NAMs) to generate information concerning chemical hazard, toxicokinetics (ADME), and exposure. The information from these major pillars of data gathering is used to inform risk assessment and classification decisions.
While the required types of data are widely agreed upon, the processes for data collection, integration and reporting, as well as several decisions on the depth and granularity of required data, are poorly standardised. To address this, we developed the Alternative Safety Profiling Algorithm (ASPA), a risk assessment workflow that allows documentation and integration of all types of information required for NGRA.
An overarching objective of ASPA is to ensure that identical data input yields identical outcomes in the hands of independent assessors. Therefore, ASPA is not just a data gathering workflow; it also considers data interdependencies and requires precise justification of intermediate decisions. This includes the monitoring and assessment of uncertainties, and the use of iterations in the workflow to reduce such uncertainties.
Several developmental neurotoxicity case studies (e.g. on desnitroimidacloprid, brequinar or picoxystrobin) will be used to showcase such iterative loops. They include (i) reduction of false negatives, (ii) hit-follow up and reduction of false positives, as well as (iii) link of hits/observations via a mechanistic rationale (e.g. an AOP) to an adverse outcome within the hazard pillar of ASPA. Moreover, they comprise in the ADME pillar of ASPA (iv) the refinement of physiology-based kinetic models, and (v) the inclusion of workflows for metabolite formation and distribution phenomena of the test item in NAMs (biokinetics modelling).
Concerning risk assessment, also iterations in the exposure pillar contribute to uncertainty reduction, by e.g. (vi) offering options to consider aggregate exposure and using probabilistic modelling approaches. A dedicated software platform /ASPA-assist) has been developed to trace and document such refinement steps.
Setting the framework for advancing NAMs in chemical safety assessment: OECD activities on DNT-IVB
— Magdalini Sachana (OECD, Environment Health and Safety Division, France)
The integration and consideration of data derived from New Approach Methodologies (NAMs) in chemical safety assessment is among the priorities of regulatory toxicology. The Organisation for Economic Co-operation and Development (OECD) provides a collaborative forum for advancing the development and adoption of mechanistically supported NAMs not only for simple, topical endpoints but also for complex endpoints such as developmental neurotoxicity (DNT).
The presentation will begin by reminding of recent achievements, including the publication of the Initial Recommendations on the Evaluation of DNT-IVB Data and the Principles of Quantitative In Vitro to In Vivo Extrapolation (QIVIVE) for this data. It will then highlight OECD’s current efforts to further strengthen regulatory confidence in DNT-IVB. These efforts involve developing an endpoint-specific Integrated Approach to Testing and Assessment (IATA) framework template that builds on existing DNT-relevant IATA case studies and the discussions of a recent OECD workshop.
The IATA framework template, specifically adapted to consider DNT-IVB data, is expected to provide a structured approach for integrating mechanistic data, helping minimise the resources required to assess the potential DNT properties of chemicals while simultaneously supporting transparent and consistent decision-making. It includes a workflow adaptable to multiple regulatory problem formulations, along with associated guidance to streamline and address critical IATA sections on data interpretation and uncertainty assessment. The IATA framework template for DNT will then be tested with new case studies and reviewed ensuring that the approach meets regulatory standards. The presentation will also explore considerations for transitioning from an IATA framework template towards defined approaches (DAs), which aim to standardise data interpretation procedures and DNT evaluations for chemicals.
To facilitate uptake, OECD has launched training activities, equipping stakeholders with the knowledge and tools needed to integrate DNT-IVB data in regulatory chemical assessments. Through these activities, OECD is laying the foundation for a science-based, internationally harmonised framework that strengthens human health protection, particularly for vulnerable populations such as children, while demonstrating the value of incorporating NAM data to address regulatory applications.
