different sources of the food, lack of standardized reference materials, and differences in the analytical methods used to quantify the levels of the allergen.
The methods used to quantify and express the doses received during clinical studies and adverse event investigations are not consistent, and this increases the uncertainty associated with the available data. The amount of an allergen consumed has been described in terms of total weight of a food consumed, total protein from an allergenic ingredient, or amount of specific allergenic proteins. Although the last description is scientifically the most accurate, it is also the most difficult to use because not all individuals are allergic to the same proteins in a food allergen and all the allergenic proteins may not have been identified for a particular food. Measurements based on the whole foods are simple, but increase the level of uncertainty because the composition of the food may vary. For example, changes in water content of a food would change the relative amount of allergenic protein present in serving sizes of a specified mass. Further, the amount of protein present as a percent of the total weight of the food may vary due to maturation, environmental factors, seasonal factors, production variability, or between different cultivars or strains. The Threshold Working Group recognized that the scientifically most accurate means of assessing exposure would be to quantify individual allergenic proteins, but concluded that the most practical approach for evaluating the currently available data is to measure exposure in terms of the total protein from a food allergen. This is also consistent with current technology for detecting food allergens.
It should also be noted that, while clinical exposures are expressed in terms of doses (i.e., g, mg, or g), allergen levels in foods are actually measured as concentrations (i.e., ppm, percent, or mg/kg). These values can be related by defining a standard serving size, usually 100 g. However, it is well documented that the actual serving eaten by consumers should be treated as a variable and a source of uncertainty when assessing exposures.
d. Challenge Studies. Clinical food challenge studies are recognized to be the most accurate way to diagnose allergies and to measure sensitivity to an allergen (Sampson, 2005). Unfortunately, the design of these food challenge studies varies widely. The lack of standardized protocols, variations in the dosing regimes (including number of doses, the interval between doses, and the relative size of the doses), and differences in the food sources (including differences in preparation and presentation) result in uncertainties when comparing the results of different studies. Double-blind placebo-controlled food challenges (DBPCFC) are considered the most robust clinical studies and data from these studies should be given preference whenever they are available. Food challenge studies are generally not designed to determine a lack of reaction (i.e., NOAEL). Instead, the doses that produce positive allergic reactions are generally reported, providing an estimate of the LOAEL for the population being studied. Despite the uncertainties associated with food challenge data from the literature, LOAELs from human clinical trials currently provide the best data for estimating population-based reactions to food allergens. In a safety assessment-based approach, the use of LOAELs instead of NOAELs would introduce additional uncertainty. A standard DBPCFC protocol has
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