Written by: Sébastien La Vieille, MD, MSc, Food and Nutrition Directorate, Health Canada; Food Science Department, Laval University; Member of the FAO/WHO expert consultation WG on risk assessment of food allergens
What are allergen thresholds?
Allergen thresholds are based on probabilistic hazard assessment using NOAEL (no observed adverse effect level) and LOAEL (lowest observed adverse effect level) data from escalating low dose, oral food challenge studies and dose-distribution modelling using various parametric statistical models. These models predict the proportion of the population (p) of individuals allergic to protein from a specific food who will experience objective allergic reactions upon oral exposure to a dose of total protein from that food (FAO/WHO, 2022).
From a clinical perspective, allergen thresholds can therefore refer to eliciting doses (EDp) that correspond to the amount of allergen (expressed in mg protein) predicted to trigger an allergic reaction in a specific percentage (p) of the allergic population. For example, the ED05 is the amount of allergen predicted to trigger an objective allergic reaction in 5% of the allergic population (and that 95% of the allergic population would not react). For peanuts, the ED05 is 2.1mg peanut protein (Houben et al., 2020).
Allergen thresholds may also refer to reference doses (RfD) when applied, for example, to help the food business operators manage the risk of unintended presence of allergens posing a health hazard. Thus, a reference dose, is an amount of allergen generally rounding the ED05 values to a significant figure, for example 2 mg for peanut.
New recommendations being considered to address PAL
In 2020, the Codex Committee on Food Labelling (CCFL) proposed to review and clarify the provisions relevant to allergen labelling in the General Standard for the Labelling of Prepackaged Foods (GSLPF) and develop guidance on precautionary allergen labelling (PAL). In approving the work, the Codex Alimentarius Commission (CAC) noted this work was linked to the work of the Codex Committee on Food Hygiene (CCFH) on allergen management and therefore asked for a close collaboration between CCFL and CCFH on this issue. The CCFL and CCFH requested FAO/WHO provide scientific advice on threshold levels for the priority allergens via an ad hoc Joint FAO/WHO expert consultation on risk assessment of food allergens (FAO/WHO expert committee). Finally, recommendations from this expert committee were made public between 2022 and 2024 in five meeting reports (Risk assessment of food allergens: part 1: review and validation of Codex alimentarius priority allergen list through risk assessment: meeting report (who.int)).
Allergen thresholds can be used in different contexts. For the FAO/WHO expert committee, the focus was placed on their application in the management of PAL. However, they can be applied in different situations such as food product recall decisions or controls of imported food products by regulators as well as advice to people with food allergies and outcome measures in food immunotherapy protocols by clinicians.
For industry, appropriate quality controls and risk mitigation measures in a context of Good Manufacturing Processes are essential before considering allergen thresholds as a risk management tool. Nevertheless, for the FAO/WHO expert committee, they are useful for risk-based approaches in determining whether or not PAL is appropriate to communicate a risk to allergic consumers.
In theory, the need for PAL could be informed by ‘action levels’ derived from RfDs: when the level of potential unintended allergen presence is above a certain concentration (i.e. action level, expressed in ppm), this would trigger the use of PAL; no PAL would be needed if levels were equal to or lower than this cut-off.
Practically, if the amount of allergen present in a realistic serving of the food coming from cross-contact could be at or above the RfD (the RfD is very close to the ED05), labelling should indicate the presence of this allergen in a PAL statement. If the amount of allergen present in a normal serving of the food will always be below the RfD, PAL should not be used. Levels of allergen below the ED05 level are predicted to provoke allergic reactions in a small percentage (by definition, less than 5%) of the allergic population and these reactions are expected to be mild in nature. At these low levels of exposure, the probability of anaphylaxis would be expected to be ≤0.25% because among the 5% of the allergic population having objective symptoms at the ED05, 5% are expected to have anaphylaxis, i.e. 0.25%. At least 80% of the anaphylactic episodes triggered at the ED05 would resolve without treatment, while >97% of the remainder would respond to first line treatment (with epinephrine). The risk of fatal reaction to an ED05 exposure in an allergic individual is estimated to be <1 per million (Turner et al., 2022). Therefore, severe allergic reactions at those levels of exposure are considered very unlikely, justifying, in this particular situation, the absence of PAL.
In addition, in some cases where no PAL would be on a food product, the expert committee has recommended that there be an indication on the label to clarify that a risk assessment has been conducted for all priority allergens in order to help allergic consumers choose safe products with confidence. The CCFL is expected to decide in the coming months whether or not to support this recommendation. However it would be welcomed by many consumers as it would provide them with additional information they need to make informed choices.
With this FAO/WHO approach, it is consequently expected that some mild allergic reactions would occur following the consumption of a product where an allergen was present at a low level but would not be labelled and allergic consumers have to be made aware of such situations. The small proportion of very sensitive individuals who regularly react to smaller amounts of allergens (with a reactivity threshold below the RfD) will not be adequately protected by the labelling on prepackaged foods and further work is required as to how best to support this group.
The challenge remains to provide solutions to both protect the rare highly sensitive consumers and not apply unnecessary restrictions to the less sensitive and much more prevalent individuals with food allergy.