Informing Risk Management for Patients With Cow's Milk Allergy Based on Threshold Dose Distributions Using Low-Dose Food Challenges

Background: The safe consumption of foods depends on their allergen content in relation to patients’ lowest observed adverse effect level (LOAEL) and no observed adverse effect level (NOAEL), as well as other factors. In the case of milk, data on LOAEL and NOAEL are limited and conflicting. Objective: To determine the threshold dose distribution and the lowest individual eliciting dose (ED) for milk in a large group of milk-allergic patients Methods: Individuals with confirmed cow's milk allergy who underwent a diagnostic or pre-oral immunotherapy open milk oral food challenge at the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between 2010 and 2015 were included. A subgroup of patients with severe milk allergy underwent a modified challenge with a 90- to 120-minute interval after a starting dose of 0.3 mg cow's milk protein. Results: A total of 866 participants (193 with diagnostic challenges and 673 with pre-oral immunotherapy challenges) were included in the study. The discrete ED₀₁ and ED₀₅, or values derived in which 1% or 5% of the respective allergic population would be predicted to experience an allergic reaction, were 1.1 to 1.9 and 4.7 to 5.6 mg milk protein, respectively, and values for cumulative doses for ED₀₁ and ED₀₅ were 0.9 to 1.8 and 5.2 to 6.2 mg milk protein, respectively. No patients, including the most severely milk-allergic individuals who underwent the modified challenge, reacted to the first 0.3 mg protein dose. Conclusion: This report provides valuable information about milk NOAELs, LOAELs, and EDs that might assist regulators in decisions about food labeling in general, and milk in particular.