Implementing New Approach Methodologies (NAMs) in food safety assessments: Strategic objectives and actions taken by the European Food Safety Authority

New Approach Methodologies (NAMs) comprise in silico and in vitro methods applied as alternative to animal testing. Even though NAMs are already fully implemented as research tools, their use in regulatory risk assessments (RA) is limited currently. To promote the regulatory uptake/acceptance of NAMs, a paradigm shift in risk assessment approaches, and a proper dialogue between risk assessors and risk managers is needed. Several reviews addressed the use of NAMs for chemical RA in generic terms, but without providing specific considerations on their use for food/feed safety assessments. Therefore, in this review, we give insights on the potential use of NAMs for regulatory purposes in the EU. We summarise relevant projects and activities on NAMs coordinated by the European Food Safety Authority (EFSA), which is the agency of the European Union that contributes to the safety of the European food and feed chain. The review informs on future developments on the use of NAMs in human health chemical RA, and touches on their use for the assessment of protein toxicity and allergenicity, as well as environmental risks. Reducing animal testing and filling some RA gaps via NAMs is almost a reality. Moreover, there is a growing body of evidence confirming that the inclusion of mechanistic information improves risk assessments. EFSA's projects address the main challenge of using intermediate effects observed in non-animal models for safety assessments, especially those linked to adverse effects that are insufficiently covered or uncovered by animal apical endpoints. •NAMs, as alternatives to animal testing, have marginal use in regulatory assessments•Challenges and opportunities for including NAMs in food/feed safety assessments•Need for paradigm evolution and guidance to use non-apical effects in risk assessment•Opportunities for safety assessment of chemicals in food/feed, proteins and allergens•EFSA is paving the way for regulatory acceptance of non-standardized NAM-based results