Beyond the 90-Day Rat Study: Is Food-Enzyme Safety Entering the Era of Next Generation Risk Assessment?

Food-enzyme safety assessment in Europe may be approaching a consequential methodological transition. In 2026, EFSA disclosed preliminary results from a retrospective review of 258 repeated-dose 90-day rodent studies submitted for food-enzyme assessments. Most revealed no safety concern; in the relatively few studies showing toxicological effects, EFSA reported that findings were associated mainly with local gastric effects of questionable human relevance or with impurities and contamination linked to manufacturing rather than the enzyme protein itself. EFSA is now examining whether routine 90-day studies can be phased out while maintaining scientific robustness, alongside a new bioinformatics pipeline for allergenicity assessment. This development coincides with the European Commission's 2026 roadmap toward phasing out animal testing for chemical safety and parallel New Approach Methodology (NAM) initiatives in the United States and United Kingdom. The strategic implication is larger than animal-test reduction: food-enzyme regulation may shift from generic in-vivo testing toward mechanism-, exposure-, source-organism-, manufacturing- and impurity-centred evidence architectures. This article examines the scientific, regulatory and industrial consequences of that transition and proposes a practical research agenda for enzyme and fermentation-derived ingredient developers.