Setting the stage for next-generation risk assessment with non-animal approaches: the EU-ToxRisk project experience
- PDF / 2,288,329 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 24 Downloads / 145 Views
LETTER TO THE EDITOR, NEWS AND VIEWS
Setting the stage for next‑generation risk assessment with non‑animal approaches: the EU‑ToxRisk project experience M. J. Moné1 · G. Pallocca2 · S. E. Escher3 · T. Exner4 · M. Herzler5 · S. Hougaard Bennekou6 · H. Kamp7 · E. D. Kroese8 · Marcel Leist2,9 · T. Steger‑Hartmann10 · B. van de Water1 Received: 21 July 2020 / Accepted: 12 August 2020 © The Author(s) 2020
Abstract In 2016, the European Commission launched the EU-ToxRisk research project to develop and promote animal-free approaches in toxicology. The 36 partners of this consortium used in vitro and in silico methods in the context of case studies (CSs). These CSs included both compounds with a highly defined target (e.g. mitochondrial respiratory chain inhibitors) as well as compounds with poorly defined molecular initiation events (e.g. short-chain branched carboxylic acids). The initial project focus was on developing a science-based strategy for read-across (RAx) as an animal-free approach in chemical risk assessment. Moreover, seamless incorporation of new approach method (NAM) data into this process (= NAM-enhanced RAx) was explored. Here, the EU-ToxRisk consortium has collated its scientific and regulatory learnings from this particular project objective. For all CSs, a mechanistic hypothesis (in the form of an adverse outcome pathway) guided the safety evaluation. ADME data were generated from NAMs and used for comprehensive physiological-based kinetic modelling. Quality assurance and data management were optimized in parallel. Scientific and Regulatory Advisory Boards played a vital role in assessing the practical applicability of the new approaches. In a next step, external stakeholders evaluated the usefulness of NAMs in the context of RAx CSs for regulatory acceptance. For instance, the CSs were included in the OECD CS portfolio for the Integrated Approach to Testing and Assessment project. Feedback from regulators and other stakeholders was collected at several stages. Future chemical safety science projects can draw from this experience to implement systems toxicology-guided, animal-free next-generation risk assessment.
M. J. Moné and G. Pallocca contributed equally to this work. Disclaimer This work reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00204-020-02866-4) contains supplementary material, which is available to authorized users. * Marcel Leist marcel.leist@uni‑konstanz.de 1
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
2
CAAT-Europe at the University of Konstanz, Constance, Germany
3
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany
4
Edelweiss Connect GmbH, Basel, Switzerland
5
German Federal Institute for Risk Assessment (BfR), Berlin, Germany
6
Technical University of Denmark, Kongens Lyngby, Denmark
7
Data Loading...
