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As discussed previously, there are substantial differences in the relative potency of different food allergens (e.g., peanut vs. soy). As noted in Appendix 2 and summarized in Table IV-5, the reported LOAELs for peanuts are considerably lower (maximum of 10 mg protein) compared to soy (maximum 522 mg protein). A single threshold for food allergens, based on the most potent food allergens, could be employed if, as a matter of risk management policy, a single threshold is considered desirable. However, this could be considered overly protective, particularly in the case of soy.


0.13 to 1.0


0.25 to 10


0.36 to 3.6

Tree Nuts

0.02 to 7.5


88 to 522


1 to 100

Table IV-5. Summary of Published LOAELs for Food Allergens


Range of LOAEL (mg protein)

Advantages. Calculation of threshold levels based on NOAELs or LOAELs and the application of appropriate uncertainty factors to estimate exposure is relatively straightforward. When there are limited data in the literature, the application of appropriate uncertainty factors provides confidence that the majority of the sensitive populations will be protected. For a number of the major food allergens, there is reasonably good agreement among the reported LOAEL values. Establishing thresholds using the safety assessment-based approach and currently available clinical data has the advantage of being directly linked to biological effects.

Limitations. There are limited clinical trial data for most allergens and most available clinical food challenge studies have not been designed to identify a NOAEL. Furthermore, an inherent, but unexamined, assumption in all clinical studies is that the reactions seen in a clinical setting are representative of the reactions to food allergen exposure that occur in the real world. Most available clinical data are primarily limited to identifying LOAELs, and there is no way to know whether doses below the observed LOAEL would still elicit a reaction. Thus, the selection of appropriate factors to account for uncertainty and inherent variability is critical in using the safety assessment-based approach. Until there is a consensus as to whether subjective symptoms are acceptable biomarkers or which objective signs are considered harmful, it appears prudent to consider as adverse any objective reaction observed in a clinical trial.

We have identified several data gaps for allergens that add to the uncertainty associated with setting thresholds. Critical areas of uncertainty and variability include:

  • Intraspecies differences. Safety assessments typically apply a 10-fold uncertainty factor to account for the variability both between individuals and variability in responses for a particular individual.

  • Sensitive population of interest. The existence and size of highly sensitive subpopulations of allergenic individuals and their lack of participation in reported clinical trials is a potential data gap and should be included in the uncertainty

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