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

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 the increased availability of innovative test methods and a better 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 this approach using case studies. These showed that fine tuning is needed, to build confidence that the proposed approach is not only scientifically correct but also satisfies the 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.

LUIJTEN Mirjam;  CORVI Raffaella;  METHA Jyotigna;  CORVARO Marco;  DELRUE Nathalie;  FELTER Susan;  HAAS Bodo;  HEWITT N;  HILTON Gina;  HOLMES Thomas;  JACOBS Miriam;  JACOBS A;  LAMPLMAIR Franz;  LEWIS Dick;  MADIA Federica Anna Carla;  MANOU Irene;  MELCHING-KOLLMUSS Stephanie;  SCHORSCH Frédéric;  SCHUTTE Katrin;  SEWELL Fiona;  STRUPP Christian;  VAN DER LAAN Jan Willem;  WOLF Douglas C.;  WOLTERINK Gerrit;  WOUTERSEN Ruud;  ZVONAR Zvonimir;  HEUSINKVELD Harm;  BRAAKHUIS Hedwig; 

2021-01-22

ACADEMIC PRESS INC ELSEVIER SCIENCE

JRC120856

0273-2300 (online),   

https://www.sciencedirect.com/science/article/pii/S0273230020302154?via%3Dihub,    https://publications.jrc.ec.europa.eu/repository/handle/JRC120856,   

10.1016/j.yrtph.2020.104789 (online),