The population threshold for soy as an allergenic food – Why did the Reference Dose decrease in VITAL 3.0?

Background: Soy is globally recognized as a commonly allergenic food. The VITAL (Voluntary Incidental Trace Allergen Labeling) Scientific Expert Panel (VSEP) of the Allergen Bureau of Australia & New Zealand used data on minimal reactive doses in low-dose clinical challenges of soy-allergic individuals to elaborate and propose the first Reference Dose for soy at 1.0 mg soy protein (based on the lower 95% confidence interval of the ED₀₅) in 2014 to guide use of precautionary allergen labeling (PAL). These data were taken from clinical challenges with soy flour or soy-based infant formula. More recently, the VSEP has examined additional data including data from challenges conducted with soy milk and used a new statistical model averaging approach to propose a new Reference Dose for soy at 0.5 mg soy protein (based on the ED₀₁). Questions have arisen about the lowering of the soy Reference Dose and the appropriate use of this new Reference Dose in risk management for soy residues especially relating to the adventitious presence of soy in other grains, legumes and pulses emanating from agricultural comingling. Scope and approach: Several factors may have contributed to the lowering of the Reference Dose for soy including the use of the ED₀₁ vs. the previous use of the 95% lower confidence interval of the ED₀₅, the use of model averaging and multiple parametric statistical models, and the incorporation of additional data including the soy milk challenge data. Soy milk may differ from other forms of soy as a challenge material. The background data were examined in greater detail in an attempt to unravel the causative factor(s) behind the lowering of the soy Reference Dose. The use of the new soy Reference Dose for allergen management of the adventitious presence of soy in other agricultural crops was examined in terms of risk to soy-allergic consumers Key finding and conclusions: The Reference Dose for soy in VITAL 3.0 decreased to 0.5 mg soy protein primarily because it was based on the ED₀₁ rather than the 95% lower confidence interval of the ED₀₅. Clinical data suggest that some soy-allergic individuals may react to soy milk but can tolerate soy flour and other soy-based foods. Perhaps, soy milk may be a more potent form of soy because of its minimal processing. But, with the current data available, there is no evidence to conclude that soy milk responders as a whole group display a relevantly different ED-distribution. The new soy Reference Dose impacts risk assessments for agricultural comingling, a form of cross contact that can be challenging to control on a national or international basis. The potential risks posed by agricultural comingling should be carefully examined in light of the new Reference Dose for soy protein.