Advancing pesticide risk assessment: the role of adverse outcome pathways and new approach methodologies – what’s next?

Introduction. In recent years, the scientific community, together with regulatory authorities, regulatory toxicology paradigm, moving from classical toxicological animal testing towards an exposure-driven risk assessment, based on mechanistic information derived from alternative methods, globally known as new approach methodologies (NAMs). The transition to the next generation risk assessment (NGRA) requires the collective effort of all involved actors. One approach addressing the needs of the NGRA is the adverse outcome pathway (AOP) concept. This construct describes a sequence of temporally and causally linked events at distinct levels of biological organization leading to an adverse health effect. The development, validation and implementation of AOPs at the regulatory level have become key objectives of several authorities.
Methods. In this paper, the AOPs and AOP networks as applied by the European Food Safety Agency are analyzed, alongside the proposed batteries of NAMs.
Results and discussion. Two case studies, (1) Parkinson’s disease and pesticide exposure, and (2) exposure to substances with endocrine-disrupting properties and the development of uterine adenocarcinoma, are described. The analysis of the entire AOP construct for each case and the assembly of the specific NAMs allowed us to identify the strengths and limitations of the AOP strategy, as well as of each proposed test. Their integration and status are assessed within the current regulatory framework.