Stakeholder input towards further refinement and consolidation of the Alternative Safety Profiling Algorithm (ASPA) for next generation risk assessment (NGRA)

@article{luijten2026stakeholder,
  title = {{Stakeholder input towards further refinement and consolidation of the Alternative Safety Profiling Algorithm (ASPA) for next generation risk assessment (NGRA)}},
  author = {Mirjam Luijten and Matthias Herzler and Femke Affourtit and Dave Allen and Muhammad Waqar Ashraf and Nicholas Ball and Elisabet Berggren and Sandra Berndt and Pierre-André Billat and Eike Cöllen and John Colbourne and Marco Corvaro and Richard Currie and Michael Guy Diemar and Hubert Dirven and Nadine Dreser and Sylvia E. Escher and Iain Gardner and Rafael Gozalbes and Stefan Hahn and Astrid Heiland and Claudia Hempt and Giel Hendriks and Oliver Henschel and Trine Husøy and Barira Islam and Keld Alstrup Jensen and Hennicke Kamp and Spyros Karakitsios and George E. N. Kass and Vikas Kumar and Robert Landsiedel and Thomas Loret and Patrik Lundquist and Catherine Mahony and Philip Marx-Stoelting and Martijn J. Moné and Ilse Ottenbros and Gladys Ouédraogo and Manuel Pastor and Magdalini Sachana and Sebastian Schmeisser and Stefan Scholz and Katrin Schütte and Kristie Sullivan and Silvia Tangianu and Adrian Tristram and Janette Turner and Mathieu Vinken and Jelle Vlaanderen and Bob van de Water and Andrew White and Marcel Leist},
  journal = {ALTEX: Alternatives to Animal Experimentation},
  year = {2026},
  month = jul,
  doi = {10.14573/altex.2603121},
  url = {https://doi.org/10.14573/altex.2603121},
  note = {CC BY},
}

TY  - JOUR
TI  - Stakeholder input towards further refinement and consolidation of the Alternative Safety Profiling Algorithm (ASPA) for next generation risk assessment (NGRA)
AU  - Mirjam Luijten
AU  - Matthias Herzler
AU  - Femke Affourtit
AU  - Dave Allen
AU  - Muhammad Waqar Ashraf
AU  - Nicholas Ball
AU  - Elisabet Berggren
AU  - Sandra Berndt
AU  - Pierre-André Billat
AU  - Eike Cöllen
AU  - John Colbourne
AU  - Marco Corvaro
AU  - Richard Currie
AU  - Michael Guy Diemar
AU  - Hubert Dirven
AU  - Nadine Dreser
AU  - Sylvia E. Escher
AU  - Iain Gardner
AU  - Rafael Gozalbes
AU  - Stefan Hahn
AU  - Astrid Heiland
AU  - Claudia Hempt
AU  - Giel Hendriks
AU  - Oliver Henschel
AU  - Trine Husøy
AU  - Barira Islam
AU  - Keld Alstrup Jensen
AU  - Hennicke Kamp
AU  - Spyros Karakitsios
AU  - George E. N. Kass
AU  - Vikas Kumar
AU  - Robert Landsiedel
AU  - Thomas Loret
AU  - Patrik Lundquist
AU  - Catherine Mahony
AU  - Philip Marx-Stoelting
AU  - Martijn J. Moné
AU  - Ilse Ottenbros
AU  - Gladys Ouédraogo
AU  - Manuel Pastor
AU  - Magdalini Sachana
AU  - Sebastian Schmeisser
AU  - Stefan Scholz
AU  - Katrin Schütte
AU  - Kristie Sullivan
AU  - Silvia Tangianu
AU  - Adrian Tristram
AU  - Janette Turner
AU  - Mathieu Vinken
AU  - Jelle Vlaanderen
AU  - Bob van de Water
AU  - Andrew White
AU  - Marcel Leist
PY  - 2026
DA  - 2026/07/01
JO  - ALTEX: Alternatives to Animal Experimentation
DO  - 10.14573/altex.2603121
UR  - https://doi.org/10.14573/altex.2603121
AB  - Next generation risk assessment (NGRA) aims to enable transparent, reproducible chemical safety assessments based on human-relevant, animal-free new approach methodologies (NAMs). The Alternative Safety Profiling Algorithm (ASPA) was developed within the ASPIS cluster to provide an algorithmic workflow that structures problem formulation, evidence integration, and decision-making across three main pillars – hazard, ADME (toxicokinetics), and exposure. A stakeholder workshop was organized to refine ASPA. Four breakout groups systematically reviewed corresponding workflow sections, identifying strengths, conceptual gaps, and opportunities for harmonization. Across groups, participants endorsed ASPA’s modular, technology-neutral nature and its focus on standardizing processes rather than prescribing specific test batteries. The hazard pillar discussions emphasized a sensitive, hypothesis-generating Tier 1, complemented by a specific, mechanistic Tier 2, capable of deriving points of departure (PoDs). ADME experts supported a physiologically based kinetic (PBK) modelling strategy, advancing from generic towards more complex models, using mechanistic information and experimental data. The exposure group proposed refinements for transparent, tiered exposure modelling, with emphasis on realistic worst-case scenarios and explicit uncertainty communication. Cross-pillar discussions highlighted the importance of feedback loops among all pillars, and the documentation of decision points to achieve consistency and defensi­bility. The workshop outcomes informed three parallel developments: (i) algorithmic refinement and re-design toward the next ASPA version, (ii) the creation of detailed guidance for each building block, and (iii) the establishment of practical case studies to demonstrate workflow implementation. This report already contains a first case study (developmental neurotoxicity assessment of desnitro-imidacloprid). These advances increase the operability, transparency, and regulatory readiness of ASPA.  Plain language summary  Next generation risk assessment (NGRA) aims to make chemical safety testing more human-rel­evant without using animals. The Alternative Safety Profiling Algorithm (ASPA) offers a structured way to combine all required data. These include information on chemical hazards, predictions on how chemicals move through the body (ADME), and estimates of exposure levels. A stakeholder workshop reviewed and improved the ASPA workflow and the associated software platform. Par­ticipants stressed the importance of the tool to make NGRA transparent and reproducible between different groups of evaluators. They suggested refinements for each part, such as clearer exposure estimates that include assessment of uncertainty. They also stressed the need for feedback between the different main modules of ASPA. An example of an ASPA evaluation was prepared to illustrate all process steps.
SN  - 1868-596X
SN  - 1868-8551
ER  -