Testing chemical compounds for carcinogenic properties is currently performed in rats. These studies cost a lot of animals, money and time. In addition, these studies are only sometimes predictive for humans. RIVM investigates a novel animal-free approach to improve carcinogenic hazard assessment while using fewer animals.
Short video about RIVM's activities researching next generation carcinogenicity testing
video
The way in which a substance can cause cancer is often divided into two categories: genotoxic and non-genotoxic. Reliable testing strategies for the genotoxic properties of a substance already exist, making extensive use of both cell-based testing and computer modelling. This does not yet exist for non-genotoxic mechanisms, for which life-time rodent studies are still performed.
RIVM's research focuses on creating an overview of how chemical substances can be carcinogenic. This overview is based on biological knowledge about human tumours and non-genotoxic mechanisms that can cause cancer. There is a wealth of data available from OECD guideline studies performed for pesticides that can be used for this purpose.
The knowledge from these studies will be organised into so-called Adverse Outcome Pathways (AOPs), which can be connected to each other in AOP networks. These networks guide the selection of appropriate in vitro and in silico methods. Together, these form a testing strategy for testing the carcinogenic properties of substances, both genotoxic and non-genotoxic. As a result, fewer animals are needed and will lead to a better, mechanism-based prediction of the risk of non-genotoxic carcinogenicity due to chemical exposure.
Key publications
| Towards a mechanism-based approach for the prediction of nongenotoxic carcinogenic potential of agrochemicals | Heusinkveld, H., Braakhuis, H., Gommans, R., Botham, P., Corvaro, M., van der Laan, J.W., Lewis, D. Madia, F., Manou, I., Schorsch, F., Wolterink, G., Woutersen, R., Corvi, R., Mehta, J., Luijten, M. | Crit Rev in Toxicol 2020; 50(9):725-39 |
| A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals | Luijten, M., Corvi, R., Mehta, J., Corvaro, M., Delrue, N., Felter, S., Haas, B., Hewitt, N.J., Hilton, G., Holmes, T., Jacobs, M.N., Jacobs, A., Lamplmair, F., Lewis, D., Madia, F., Manou, I., Melching-Kollmuss, S., Schorsch, F., Schutte, K., Sewell, F., Braakhuis, H. | Regul Toxicol and Pharmacol 2020; 104789 |