EFSA project Development of roadmaps for action on NAMs in risk assessment

Results from animal studies, which are often requested for risk assessment purposes, are of little or no use in corroborating the observed toxicity with insights into the underlying mechanism at the molecular level. Alternative, new-approach methodologies (NAMs) combining human-relevant in-vitro methods and computational (in-silico) approaches hold much promise to fill this gap. 

The main objective of a project on behalf of EFSA is to propose priorities regarding the incorporation of NAMs into regulatory hazard and risk characterization of chemicals in food and feed. For this purpose, focuses were identified from five relevant research areas, namely toxicodynamics, toxicokinetics, exposome, susceptible human subpopulations and data integration. Special attention was paid to the degree of estimated regulatory readiness of the various alternative methods and concepts, starting from the research level to acceptance by the authorities via in-situ validation. To analyze the impact of the five research areas on the reduction, refinement and replacement of animal testing (3Rs), challenges and blockers were identified as well as data gaps, some of which were significant.

The result was the recommendation of seven research activities required for NAMs to be implemented in EFSA's scientific assessment process. The recommended measures include a number of proof-of-concept studies benchmarking the readiness of specific technologies and models with regard to the toxicodynamics and toxicokinetics of compounds, but also enabling hazard assessment for particularly susceptible human subpopulations. In addition, the applicability domain of these models is planned to be extended to compounds in food and feed. The case studies have been specifically designed to build confidence in NAM-based risk assessment and thus to improve the use and acceptance of these technologies.