Glutamate: Safe and Adequate Intake Levels for Infants-

Toxicological risk assessment of food ingredients has traditionally relied on identifying a no-observed-adverse-effect level (NOAEL) or benchmark dose (BMD), followed by the application of default uncertainty factors (UFs) to derive health-based guidance values (HBGVs) such as the acceptable daily intake (ADI). While effective for conventional food additives, this approach may be inappropriate for nutrients and intrinsic food components with established physiological functions. This paper critically explores these limitations using free glutamate as a central example, alongside additional cases relevant to infant nutrition, including vitamin C, iodine, and human milk oligosaccharides (HMOs). Data on free glutamate in human milk show that breastfed infants habitually ingest amounts far exceeding additive-based ADIs without adverse effects, underscoring the limitations of applying default uncertainty factors and classical toxicological paradigms to endogenous nutrients. Comparable considerations apply to protein hydrolysates and amino acid-based infant formulas evaluated by EFSA, where growth, tolerance, and compositional suitability are integral to safety assessment. Overall, nutrient safety evaluation requires an integrative, physiology-informed framework that incorporates realistic exposure, developmental stage, and metabolic competence. Breast milk provides a biologically relevant reference, supporting a proportionate and science-based application of toxicological principles in infant nutrition.