Appendix E
Definitions
Acceptable level of risk: A risk management decision regarding the degree of risk that would be acceptable within the affected population.
Allergen-specific IgE (sIgE): An IgE that recognizes a specific allergen and that is formed by the immune systems of some individuals after they have been exposed to that allergen in food. Also referred to in the text as food-specific IgE.
Allergy/allergic disease: A disease caused by immunologic dysfunction that falls under one of two key classifications: immunoglobin E (IgE)-mediated or non-IgE-mediated.
Anaphylaxis: An acute, potentially life-threatening syndrome with multisystemic manifestations due to the rapid release of inflammatory mediators.
Atopic disorder: Disorder characterized by exaggerated or hypersensitive immune reactions to foreign antigens.
Atopic march: Refers to the idea that atopic disorders progress over time from eczema (i.e., atopic dermatitis) to asthma.
Atopy patch test (APT): A test performed in a manner similar to patch testing that is routinely used for evaluation of allergic contact dermatitis, except that foods are used. The food, presented as a fresh extract or powder, is generally placed under an aluminum disc on the skin for 48
hours then removed. The final test result is determined at 72 hours after application. Current guidelines do not recommend the APT for the routine diagnosis of food allergies.
Auto-injector of epinephrine: A device used in first-aid management to self-inject epinephrine.
Basophil activation test (BAT): A test conducted by exposing the basophils in a test tube to various concentrations of the allergen to be tested, either an extract or individual component proteins in the test tube. The readout is the number of cells responding, or the concentration of allergen at which 50 percent of the cells respond. About 10 percent of people are BAT nonresponders, even though they are allergic and have positive skin tests. The test is a functional assay akin to a provocation test, such as a skin prick test.
Basophils (basophilic granulocytes): The least abundant of the granulocytes (the others being neutrophils and eosinophils). Basophils can release histamine, lipid mediators, and cytokines in response to the aggregation of their cells surface FceRI, which is induced when IgE bound to these FceRI recognizes specific allergens, including those from foods. Unlike mast cells, basophils mature in the bone marrow and circulate in the blood, but can enter tissues at sites of allergic inflammation.
Component resolved diagnostics: A test sometimes referred to as molecular testing. This test involves measuring sIgE against individual allergenic food proteins.
Cross-contact: A situation in which an unintended allergen may be present in an otherwise allergen-free food because of contact between the unsafe and safe foods.
Cytokines: Small proteins produced by various immune cells and other cell types that carry signals to facilitate communication and interaction between cells.
Desensitization: A state of clinical and immunological nonresponsiveness to an allergen, including food allergens, that can be induced by the careful, physician-guided administration of gradually increasing amounts of the offending allergen over a relatively short period of time (hours to days). The maintenance of such desensitization typically requires continued regular exposure to the offending allergen (also see Tolerance).
Epinephrine: Also known as adrenaline, first-line therapy for food-induced anaphylaxis. Recommended to be injected intramuscularly.
Epitopes: Specific fragments of food allergens (antigens) that the immune system recognizes; if recognized by IgE bound to FceRI on the surface of mast cells and basophils, epitopes can trigger an allergic reaction that may include anaphylaxis.
Exposure assessment: An action that plays an essential role in determining whether the hazardous properties of a substance will translate to adverse health effects. For foods, the exposure assessment estimates the amounts (or range of amounts) of the hazard that are likely to be consumed. If these amounts exceed a Reference Dose or the established maximum level in foods (established using a hazard assessment), then a risk of adverse health consequences to the exposed (sub)population is predicted. In contrast, an exposure at or below the Reference Dose or maximum level in foods is assumed to be safe for the vast majority of individuals. In the case of food allergens, the Reference Dose could also be used as an action level to determine when precautionary allergen labeling should be applied to a product package. (Also see Hazard identification and hazard characterization and Reference Dose.)
FceRI: The high-affinity receptor for IgE that binds IgE and thereby permits cells bearing FceRI on their surface (e.g., mast cells, basophils, some dendritic cells, and macrophages) to become “sensitized” so that they can be activated to release inflammatory mediators by allergens recognized by the bound IgE. For the FceRI to initiate the cell signaling that results in activation of mast cells and basophils to release their mediators requires that the receptors are aggregated when their bound IgE reacts with allergens that are at least bivalent (e.g., have two epitopes that can bind IgE). This permits such allergens to bridge adjacent IgE molecules and to aggregate the FceRI receptors that bind such IgE.
Food: Any substance—whether processed, semiprocessed, or raw—that is intended for human consumption. Food includes drinks, chewing gum, food additives, and dietary supplements.
Food allergens: The components within foods that trigger adverse immunologic reactions; these are most often specific glycoproteins that can interact with the body’s immune cells in a way that initiates the development of a food allergy.
Food allergy: An adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food, and that can be either IgE-mediated or non-IgE-mediated.
Food intolerance: An adverse reaction to foods or food components that lacks an identified immunologic pathophysiology.
Food protein-induced enterocolitis syndrome and food protein-induced allergic proctocolitis: Non-IgE-mediated disorders that lack current means of simple laboratory testing to identify causal foods or to confirm the diagnosis. Guidelines suggest using the medical history, resolution of signs and symptoms during dietary elimination, and recurrence of signs and symptoms upon exposure, for example during an oral food challenge, as a means of diagnosis.
Hazard: An inherent property of an agent or situation having the potential to cause adverse effects when an organism, system, or given population is exposed to that agent.
Hazard identification and hazard characterization: The two components of the hazard assessment process. Hazard identification includes a determination that the substance with the hazardous properties is present, but also more generally refers to the identification of the type and nature of the adverse effects that an agent can cause in an organism, system, or given population. In the hazard identification of an allergenic food, the prevalence and severity of the specific food allergy would be considered. Hazard characterization involves a qualitative and, wherever possible, quantitative description of the inherent property of an agent or situation having the potential to cause adverse effects. Hazard characterization encompasses the dose–response relationship. A hazard assessment (involving both hazard identification and hazard characterization) can be used to derive safe levels of exposure, for instance through the elaboration of a Reference Dose.
Immunoglobulin E (IgE): An antibody that can trigger intense inflammatory reactions. IgE causes the IgE-mediated allergic response by binding strongly to IgE receptors (FceRI) found on the surface of mast cells and basophils, and triggering these cells to release powerful inflammatory mediators once the cell-bound IgE recognizes the offending food allergen.
Lowest-observed-adverse-effect level (LOAEL): The lowest dose of a hazard (e.g., allergen, expressed as milligrams (mg) of total protein from the allergenic food) that can provoke an observable reaction in an individual or population. Also known as the minimal eliciting dose.
Mast cells: Cells derived from hematopoietic precursors that mature after migrating into essentially all vascularized tissues, where they can reside for long periods of time. Mast cells are present within the mucosal tissues of the entire gastroinstestinal tract (and many other anatomical sites, including the skin and airways) and contain cytoplasmic granules rich in histamine, proteoglycans (depending on the mast cell population, these consist of heparin and/or chondroitin sulfates), serine proteases (depending on the mast cell population, these can consist of carboxypeptidase A3, tryptases and/or chymase). Upon activation by IgE and specific antigens (including food allergens), mast cells can release such granule-associated inflammatory mediators and also secrete newly synthesized lipid mediators and cytokines. Mast cells also can be activated by diverse agents that act independently of IgE, which can result in the release of the same products produced by mast cells activated through IgE.
No-observed-adverse-effect level (NOAEL) or threshold: The highest dose of a hazard (e.g., allergen, expressed as mg of total protein from the allergenic food) that will not provoke an observable reaction in an individual or population.
Objective response: A reaction that can be independently verified by a clinically trained observer (e.g., urticaria [hives], vomiting, flushing, angioedema).
Oral food challenge (OFC): A feeding test that typically involves a gradual, medically supervised ingestion of increasingly larger doses of the food being tested as a possible food allergen. Guidelines recommend using the OFC to diagnose food allergy, particularly in individuals whose clinical history and other test results do not definitively establish the diagnosis of food allergy. There are three types of OFCs depending on the protocol. An open OFC is one where the food is in its natural form; a single-blind OFC is one where the food is masked from the patient’s perspective so less patient bias occurs because of anxiety; a double-blind, placebo-controlled oral food challenge (DBPCOFC) involves masking the tested allergen and feeding it or indistinguishable placebo randomly without the patient or observer knowing if the allergen or placebo is being tested. A DBPCOFC is considered the “gold standard” for diagnosis of food allergy.
Pollen-associated food allergy syndrome (oral allergy syndrome): A type of food allergy with signs and symptoms that include itching or swelling of the lips, mouth, or throat in response to eating certain raw fruits and vegetables that typically develops in adults with hay fever. The specific IgE antibodies formed exhibit reactivity with both proteins found in pollens and similar proteins found in certain fruits and vegetables.
Reference Dose: The lowest dose of a hazard (e.g., allergen, expressed in mg of total protein from the allergenic source) that is predicted to elicit symptoms of a reaction when ingested by a defined, small percentage of the population of individuals who are known to experience adverse reactions to that hazard.
Risk: The probability of an adverse effect in an organism, system, or (sub) population caused under specified circumstances by exposure to an agent.
Risk characterization: A process that can be used to assess the likelihood of risk even in cases where a Reference Dose or maximum level has not been established. The risk characterization is the determination of quantitative probability, including attendant uncertainties, that adverse health effects will occur in a given individual or (sub)population, under defined conditions of exposure.
Safety: The control of recognized hazards to achieve an acceptable level of risk.
Sensitization: A condition in which an individual produces detectable IgE to a particular allergen or allergens. It precedes and is required for the cell manifestations of a food allergy, but not all individuals with detectable IgE will experience a food allergy reaction to the allergen recognized by that IgE.
Skin prick test: An allergy detection test performed by puncturing the surface of the skin to introduce an allergen and evaluating the area of the induced wheal (small swelling) and flare (redness) responses that can be measured.
Subjective response: A mild transitory reaction that cannot be independently confirmed by a clinically trained observer (e.g., palatal itching or stomach cramping).
T cells: Lymphocytes produced by the thymus that guide many aspects of the immune system, particularly its adaptability and ability to recognize threats.
Tolerance: A state of relatively unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response. It can be natural (e.g., to the body’s own proteins) or acquired (e.g., to
