A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals

Mirjam Luijten*, Raffaella Corvi, Jyotigna Mehta, Marco Corvaro, Nathalie Delrue, Susan Felter, Bodo Haas, Nicola J. Hewitt, Gina Hilton, Thomas Holmes, Miriam N. Jacobs, Abigail Jacobs, Franz Lamplmair, Dick Lewis, Federica Madia, Irene Manou, Stephanie Melching-Kollmuss, Frederic Schorsch, Katrin Schütte, Fiona SewellChristian Strupp, Jan Willem van der Laan, Douglas C. Wolf, Gerrit Wolterink, Ruud Woutersen, Zvonimir Zvonar, Harm Heusinkveld, Hedwig Braakhuis

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Citations (Scopus)


Currently the only methods for non-genotoxic carcinogenic hazard assessment accepted by most regulatory authorities are lifetime carcinogenicity studies. However, these involve the use of large numbers of animals and the relevance of their predictive power and results has been scientifically challenged. With increased availability of innovative test methods and enhanced understanding of carcinogenic processes, it is believed that tumour formation can now be better predicted using mechanistic information. A workshop organised by the European Partnership on Alternative Approaches to Animal Testing brought together experts to discuss an alternative, mechanism-based approach for cancer risk assessment of agrochemicals. Data from a toolbox of test methods for detecting modes of action (MOAs) underlying non-genotoxic carcinogenicity are combined with information from subchronic toxicity studies in a weight-of-evidence approach to identify carcinogenic potential of a test substance. The workshop included interactive sessions to discuss the approach using case studies. These showed that fine-tuning is needed, to build confidence in the proposed approach, to ensure scientific correctness, and to address different regulatory needs. This novel approach was considered realistic, and its regulatory acceptance and implementation can be facilitated in the coming years through continued dialogue between all stakeholders and building confidence in alternative approaches.

Original languageEnglish
Article number104789
JournalRegulatory Toxicology and Pharmacology
Publication statusPublished - Dec 2020

Bibliographical note

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  • 3Rs
  • Alternative approaches to animal testing
  • Carcinogenicity
  • Human health risk assessment
  • Mode of action
  • NAMs
  • New approach methodologies
  • Non-genotoxic carcinogens


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