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.
Bibliographical noteFunding Information:
The authors wish to thank Fabrice Broeckaert, Kathryn Guyton and Andrea Terron for their valuable contributions during the workshop. They thank Eric Gremmer for providing a graphic design of the mechanism-based approach to cancer risk assessment. The workshop ?Mechanism-based approach to cancer risk assessment incorporating 3Rs principles? was funded by the European Partnership for Alternative Approaches to Animal Testing (EPAA). Disclaimer ? the authors are experts representing their own opinions and not their institutions. H. Braakhuis, H. Heusinkveld, N. Hewitt, and M. Luijten were compensated by EPAA for the time spent in the preparation, review and submission of this manuscript. About the EPAA: EPAA is a Public-Private Partnership across 7 industry sectors and between the European Commission and Industry stakeholders. Launched in 2005, it gathers 37 companies, 8 European trade federations and 5 Directorates-General of the European Commission. Further information is available on www.epaa.eu.com.
The authors wish to thank Fabrice Broeckaert, Kathryn Guyton and Andrea Terron for their valuable contributions during the workshop. They thank Eric Gremmer for providing a graphic design of the mechanism-based approach to cancer risk assessment. The workshop ‘Mechanism-based approach to cancer risk assessment incorporating 3Rs principles’ was funded by the European Partnership for Alternative Approaches to Animal Testing (EPAA).
© 2020 The Authors
- Alternative approaches to animal testing
- Human health risk assessment
- Mode of action
- New approach methodologies
- Non-genotoxic carcinogens