A Codex-Informed Hazard Screening and Qualitative Safety Assessment Framework for Essential Oil-Bacteriophage Combinations in Food Systems

• Codex-informed principles-based workflow for screening EO–phage food-use combinations • QSAR-based constituent profiling and dossier-based phage screening with explicit STOP gates • Consolidated hazard tiers plus an optional qualitative L × C screening layer for transparent prioritisation • Conservative screening matrix maps all EO–phage pairs to a negligible-low screening output band • Sensitivity analysis shows screening outputs shift under alternative likelihood-category assumptions This study investigates whether essential oil-bacteriophage combinations may be screened for food safety using a transparent qualitative approach, therefore filling a gap in which synergy is frequently reported for efficacy but seldom examined for safety. Hazards of main essential oil elements were profiled in the OECD QSAR Toolbox, translated into qualitative concern tiers, and aggregated to the oil level using composition weighting and dominance principles. Bacteriophage safety was evaluated by dossier using eight criteria: genetic integrity, manufacturing and process quality, stability, host range, effectiveness in food-like settings, regulatory precedent, and uncertainty, with specific STOP criteria for genomic or manufacturing failures. A conservative maximum rule was used to combine the essential oil and phage tiers, which were then mapped to screening labels using an FAO/WHO-style matrix with likelihood categories for purely lytic, Good Manufacturing Practice-grade phages. When applied to oregano, thyme, and dittany against Escherichia coli , all combinations mapped to Low screening output, within the qualitative and conservative boundaries of the framework, despite oregano and dittany presenting Moderate–High essential oil tiers due to cautious QSAR alerts. The methodology provides an early-stage safety screen that supports feasibility under rigorous inclusion criteria, while remaining preliminary and hypothesis-generating. Validation in food matrices and EO-phage compatibility (titre-stability) confirmation under intended-use circumstances will be required before practical implementation; formulation solutions may be considered if titre-stability data reveal a major loss of infectivity at the desired EO dose..