symptoms should be considered adverse effects. For example, can eczema be seen as a “safer” reaction than angioedema? Unlike well-defined toxicity endpoints, reactions to allergenic food ingredients are part of a wide spectrum of severity that includes trivial injury, objective systemic reactions, anaphylaxis, and death. Further, allergic reactions may involve multiple organ systems. For example, in Scibilia et al. (2006) 62% of responses involved more than one organ system.
Subjective symptoms may be good indicators of a subsequent objective reaction, i.e., subjective symptoms may precede or signal objective signs in a dose-dependent manner (Moneret-Vautrin, 2004). However, most challenge studies base their LOAEL determinations on the first objective sign rather than a subjective symptom. For example, although the Hourihane et al. (1997a) study reported a threshold for peanut proteins in the milligram range, mild subjective reactions were noted in two individuals at doses of 100 g of peanut protein. Other studies do not report specific types of reactions but rather characterize reactions as mild, moderate, or severe. For example, a retrospective review of 253 failed challenges at one clinic showed that the initial reaction was severe in 72 (28%) and moderate in 88 (33%) of the challenges (Perry et al., 2004). There is only one published study (Wensing et al., 2002b) that evaluated reproducible subjective symptoms.
Currently, there is no universally accepted endpoint or response that can be used to predict significant harm from an allergic reaction. Anaphylaxis, a clearly significant endpoint, is a syndrome which is poorly described and subject to variable interpretation (Sampson et al., 2005). Moreover, anaphylactic reactions are at one extreme of a continuum of severity. There are a number of additional factors (e.g., use of medicine, alcohol consumption, anxiety) that can significantly reduce or potentiate the impact of exposure to an allergen. Given this combination of factors, a particular dose could result in mild symptoms one day and life-threatening reactions the next.
5. Anecdotal Evidence Although a great deal of attention has been focused on the use of challenge studies to determine threshold doses or reaction patterns for food allergens, anecdotal reports of individuals suffering life-threatening allergic reactions from minute exposures to food allergens suggests that there may not be a measurable allergen threshold level, especially for sensitive individuals. For example, literature reports have linked kissing (Hallett et al., 2002; Steensma, 2003; Eriksson et al., 2003) and exposure to airborne particles (Crespo et al., 1995; Casimir et al., 1997; Sackesen and Adalioglu, 2003) to allergic reactions. Although in many of these cases the amount of allergen exposure cannot be assessed, it is conceivable that the whole food exposure level needed to elicit a harmful reaction is extremely low. In this context, it should be noted that the statistical model developed by Bindslev-Jensen et al. (2002) suggested that concentrations as low as 700 ng for peanut and in the low microgram ranges for egg, soy flour, and cow’s milk may elicit a reaction in one in a million allergic individuals. Although this model also suggests that a majority of allergic individuals would likely tolerate food allergen concentrations in the milligram range, it supports the anecdotal evidence that very low
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