The long way from raw data to NAM-based information: Overview on data layers and processing steps

ALTEX, vol. 42, pp. 167–180

Abstract

Toxicological test methods generate raw data and provide instructions on how to use these to determine a final outcome such as a classification of test compounds as hits or non-hits. The data processing pipeline provided in the test method description is often highly complex. Usually, multiple layers of data, ranging from a machine-generated output to the final hit definition, are considered. Transition between each of these layers often requires several data processing steps. As changes in any of these processing steps can impact the final output of new approach methods (NAMs), the processing pipeline is an essential part of a NAM description and should be included in reporting templates such as the ToxTemp. The same raw data, processed in different ways, may result in different final outcomes that may affect the readiness status and regulatory acceptance of the NAM, as an altered output can affect robustness, performance, and relevance. Data management, pro­cessing, and interpretation are therefore important elements of a comprehensive NAM definition. We aim to give an overview of the most important data levels to be considered during the devel­opment and application of a NAM. In addition, we illustrate data processing and evaluation steps between these data levels. As NAMs are increasingly standard components of the spectrum of toxi­cological test methods used for risk assessment, awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes. Plain language summary Toxicological test methods initially generate raw data. These need to be further processed to determine a final outcome, such as the classification of test compounds as hits or non-hits. The pro­cessing of the raw data is often highly complex and proceeds stepwise. This process generates many layers of data connected by several processing steps. Any change to these processing steps can impact the final output of new approach methods (NAMs). This means that the same raw data, processed in different ways, may result in different final outcomes. Data management, processing and interpretation are therefore considered important elements of a comprehensive NAM definition. We illustrate data processing and evaluation steps that play an important role. Awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes.

Authors 35

1. Jonathan H. Blum

   University of Konstanz

   Affiliation as printed

   In vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany

2. Markus Brüll

   University of Konstanz

   Affiliation as printed

   In vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany

3. Jan Georg Hengstler

   TU Dortmund University · Leibniz Research Centre for Working Environment and Human Factors

   Affiliation as printed

   Leibniz Research Centre for Working Environment and Human Factors (IfADo), Technical University of Dortmund, Dortmund, Germany

4. Daniel Reto Dietrich

   University of Konstanz

   Affiliation as printed

   Human and Environmental Toxicology, University of Konstanz, Konstanz, Germany

5. Andreas J Gruber

   University of Konstanz

   Affiliation as printed

   Department of Biology, University of Konstanz, Konstanz, Germany

6. Michele Dipalo

   Italian Institute of Technology

   Affiliation as printed

   IIT Istituto Italiano di Tecnologia, Genoa, Italy

7. Udo Kraushaar

   Natural and Medical Sciences Institute

   Affiliation as printed

   NMI Natural and Medical Sciences Institute at the University of Tuebingen, Reutlingen, Germany

8. Iris Mangas

   European Food Safety Authority

   Affiliation as printed

   EFSA - European Food Safety Authority, PREV Unit, Parma, Italy

9. Andrea Terron

   European Food Safety Authority

   Affiliation as printed

   EFSA - European Food Safety Authority, PREV Unit, Parma, Italy

10. Ellen Fritsche

    University of Basel · Swiss Centre for Applied Human Toxicology

    Affiliation as printed

    Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

    SCAHT - Swiss Centre for Applied Human Toxicology, Basel, Switzerland

11. Philip Marx‐Stoelting

    Federal Institute for Risk Assessment

    Affiliation as printed

    German Federal Institute for Risk Assessment (BfR), Berlin, Germany

12. Barry J. Hardy

    Edelweiss Connect (Switzerland)

    Affiliation as printed

    Edelweiss Connect GmbH, Basel, Switzerland

13. Andreas G. Schepky

    Beiersdorf (Germany)

    Affiliation as printed

    Beiersdorf AG, Global Toxicology, Hamburg, Germany

14. Sylvia E. Escher

    Fraunhofer Institute for Toxicology and Experimental Medicine

    Affiliation as printed

    In silico Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany

15. Thomas Härtung

    Johns Hopkins University · University of Konstanz

    Affiliation as printed

    CAAT-Europe, University of Konstanz, Konstanz, Germany

    Doerenkamp-Zbinden-Chair for Evidence-based Toxicology, Center for Alternatives to Animal Testing (CAAT), Johns Hopkins University, Bloomberg School of Public Health and Whiting School of Engineering, Baltimore, MD, USA

16. Robert Landsiedel

    BASF (Germany)

    Affiliation as printed

    BASF SE, Experimental Toxicology and Ecology, Ludwigshafen am Rhein, Germany

17. Alex Odermatt

    University of Basel · Swiss Centre for Applied Human Toxicology

    Affiliation as printed

    Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

    SCAHT - Swiss Centre for Applied Human Toxicology, Basel, Switzerland

18. Magdalini Sachana

    Organisation de Coopération et de Développement Economiques

    Affiliation as printed

    Organisation for Economic Co-operation and Development (OECD), Environment Health and Safety Division, Paris, France

19. Katharina Koch

    Leibniz Institute of Environmental Medicine

    Affiliation as printed

    DNTOX GmbH, Duesseldorf, Germany

    IUF - Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany

20. Stefan Masjosthusmann

    Bayer (Germany)

    Affiliation as printed

    Regulatory Toxicology, Research and Development, CropScience, Bayer AG, Monheim am Rhein, Germany

21. Kathrin Bothe

    Bayer (Germany)

    Affiliation as printed

    Regulatory Toxicology, Research and Development, CropScience, Bayer AG, Monheim am Rhein, Germany

22. Stefan Schildknecht

    Albstadt-Sigmaringen University

    Affiliation as printed

    Albstadt-Sigmaringen University, Faculty of Life Sciences, Sigmaringen, Germany

23. Mario Beilmann

    Boehringer Ingelheim (Germany)

    Affiliation as printed

    Boehringer Ingelheim Pharma GmbH & Co. KG, Global Nonclinical Safety & DMPK, Biberach an der Riss, Germany

24. Joost B. Beltman Aachen Division of Cell Systems and Drug Safety Leiden Academic Centre for Drug Research

    Leiden University

    Affiliation as printed

    Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

25. Suzanne Fitzpatrick

    United States Food and Drug Administration

    Affiliation as printed

    US Food and Drug Administration, College Park, MD, USA

26. Aswin Mangerich

    University of Potsdam

    Affiliation as printed

    Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany

27. Markus Rehm

    University of Stuttgart

    Affiliation as printed

    Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany

28. Silvia Tangianu

    University of Konstanz

    Affiliation as printed

    CAAT-Europe, University of Konstanz, Konstanz, Germany

    In vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany

29. Franziska Maria Zickgraf

    BASF (Germany)

    Affiliation as printed

    BASF SE, Experimental Toxicology and Ecology, Ludwigshafen am Rhein, Germany

30. Hennicke Kamp

    BASF (Germany)

    Affiliation as printed

    BASF Metabolome Solutions GmbH, Berlin, Germany

31. Gerhard A. Burger Aachen Division of Cell Systems and Drug Safety Leiden Academic Centre for Drug Research

    Leiden University

    Affiliation as printed

    Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

32. Bob van de Water Aachen Division of Cell Systems and Drug Safety Leiden Academic Centre for Drug Research

    Leiden University

    Affiliation as printed

    Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

33. Nicole Kleinstreuer

    National Institute of Environmental Health Sciences

    Affiliation as printed

    National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, NIEHS, RTP, NC, USA

34. Andrew White

    Unilever (United Kingdom)

    Affiliation as printed

    Unilever Safety and Environmental Assurance Centre, Bedfordshire, UK

35. Marcel Leist

    University of Konstanz

    Affiliation as printed

    CAAT-Europe, University of Konstanz, Konstanz, Germany

    In vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany