Toxicological risk assessment of plant protection products (PPP) is currently carried out with the principal input from regulatory toxicology studies following OECD test guidelines, with little input from epidemiological data. An EFSA-commissioned systematic review of pesticide epidemiological studies (Ntzani et al. in Literature review on epidemiological studies linking exposure to pesticides and health effects. EFSA supporting publication 2013:EN-497, 2013) revealed statistically significant associations, among others, between pesticide exposures, and Parkinson's disease and childhood leukemia. Thereafter, EFSA launched a project with a mandate for the plant protection products and their residues (PPR) Panel to set the ground for the use of epidemiological data in the risk assessment of pesticides, as requested by Regulation (EC) 1107/2009. The project culminated with the publication of two EFSA's scientific opinions on the potential contribution of experimental investigations and epidemiological studies in PPP risk assessment and with the scientific conference held on 20 November 2017, in Parma, Italy. The application of modern methodologies in exposure assessment, toxicology and epidemiology would improve the pesticide risk assessment process and support a mechanistic shift for the integration of these three disciplines under a novel paradigm in risk assessment. The application of the adverse outcome pathway (AOP) conceptual framework to this approach would contribute to gain insight into the biological plausibility of a hazard identified in epidemiological or experimental studies and would inform an Integrated Approach to Testing and Assessment (IATA) within a regulatory context.