Editorial: The safety assessment of novel foods and new nutrient sources

Abstract

An important theme that emerged from this Research Topic is the toxicological safety assessment of novel foods including genotoxicity and repeated dose toxicity. Schreppler et al., employed a standard battery of in vitro genotoxicity tests (bacterial reverse mutation assay, in vitro mouse lymphoma TK gene mutation assay, and in vitro micronucleus assay) to assess the genotoxic potential of short-, medium-, and longchain triacylglycerides 1 . This synthetic mixture of triacyglycerides showed no evidence of mutagenic, clastogenic, or aneugenic activity. Overall, the available data indicated that this novel food did not exhibit genotoxic potential under the tested conditions supporting its safety as a dietary fat ingredient. Mahadevan et al., demonstrated the safety of Hericium erinaceus and Trametes versicolor mushroom powders in acute and subchronic oral toxicity studies, as well as in in vitro and in vivo genotoxicity assays 2 .Long-term safety of the consumption of novel foods was further addressed by Punvittayagul et al., who evaluated formulated Thai rice instant granules containing turmeric extract and Phyllanthus emblica fruit pulp in a 6-month repeated-dose oral toxicity study and revealed no adverse ePects 3 . Given the presence of plant-based bioactive compounds, the expression profile of hepatic antioxidant genes was examined and found to be upregulated. Especially their work on molecular docking to identify binding aPinity interactions between major bioactive compounds and key antioxidant enzymes provides an example of the application of mechanistic toxicology to gain insights into the antioxidant potential of these bioactive constituents present in the granules.Mechanistic insights into the antioxidant potential of bioactive compounds in novel foods were further provided by Giambastiani et al., who investigated the ePects of dietary supplementation with the microalga Chlorella vulgaris in an animal study 4 . The findings showed elevated activity of hepatic xenobiotic-metabolizing cytochrome P450 (CYP) enzymes together with antioxidant and detoxification enzymes without signs of liver and kidney toxicity. The antioxidant potential of C. vulgaris was supported by compositional data indicating its richness in phenolic compounds and carotenoids. Additionally, their work illustrated anti-inflammatory and antioxidant ePects of C. vulgaris in a murine model of chronic pulmonary inflammation. These findings further support the need for comprehensive toxicological evaluations on the long-term ePects of novel foods containing bioactive compounds with pharmacological activities.Another important theme emerging from this Research Topic concerns the complexity of the safety assessment in cases of products of cellular agriculture and the increasing importance of the application of New Approach Methodologies (NAMs). Felicianna et al., investigated the chemical characterization and toxicity of plant cell cultures from scurvy grass (Cochlearia danica) and rowan (Sorbus aucuparia) and demonstrated that they are nutritionally comparable to other berry cell lines without toxic ePects 5 . By applying proteomics analysis to identify potential allergens, the study showcases how NAMs are incorporated in the allergenicity safety assessment of novel foods. Their findings also emphasized the need for further work to evaluate the outcomes of proteomics, and the ePects from phytohormone accumulation used in the growth media on the quality and safety of these plant cell culture foods.The allergenicity assessment of novel foods was also addressed by Calcinai et al., who performed protein profiling of chia seeds (Salvia hispanica) followed by in-silico homology analysis between identified chia peptides and sesame protein sequences 6 . The potential cross-reactivity with characterised linear epitopes from sesame allergens was further corroborated in vitro by IgE-binding assays using sera from sesame-allergic individuals. This study highlights the challenges faced in the assessment of the allergenic potential of novel proteins including the lack of comprehensive protein sequence data and the insuPicient characterization of potential allergenic epitopes.Complementing these studies, Laganaro et al. reviewed the data requirements for allergenicity safety assessment of novel foods within the EU framework, identifying key uncertainties and research needs 7 . The assessment should first consider the nature of the novel food, whether proteins are involved in its production, and whether its source is known to be allergenic. Literature findings, together with protein digestibility and stability data, also inform the evaluation of its allergenic potential. Where uncertainty remains, a tiered approach is applied to investigate potential cross-reactivity with known allergens, encompassing in silico, in vitro and, where necessary, in vivo approaches. The review underscores the value of integrating bioinformatic predictions with experimental validation to strengthen the evidence base for allergenicity assessment, while also highlighting the need for consensus on the interpretation of results, standardised and validated methods, and development of de novo sensitization assays.Addressing limitations and data gaps in the safety assessment of novel foods is crucial for food innovation without compromising public health. The next generation of safety assessment is expected to increasingly integrate NAMs and AI, while addressing the need for method standardisation and validation to support fit-for-purpose regulatory decisionmaking. Overall, the contributions assembled in this Research Topic reflect the breadth of approaches for toxicological and allergenicity assessment and illustrate the ongoing evolution towards more mechanistic, predictive and biologically relevant methodologies.Author contributions MG: Writing -original draft, Writing -review and editing, LP: Writing -review and editing