**1. Introduction**

The subset of food-allergic patients sensitive to minute amounts of foods is facing problems of food safety every day [1]. To protect them from accidental ingestions, regulatory authorities have put in place legislative measures prescribing the declaration of food allergen ingredients in the respective food labels [2]. Beyond food allergen ingredients, precautionary labelling of allergens (PAL) has been adopted by food producers as additional level of protection when food allergens may contaminate foods. PAL conveys an

**Citation:** Fierro, V.; Marzano, V.; Monaci, L.; Vernocchi, P.; Mennini, M.; Valluzzi, R.; Levi Mortera, S.; Pilolli, R.; Dahdah, L.; Calandrelli, V.; et al. Threshold of Reactivity and Tolerance to Precautionary Allergen-Labelled Biscuits of Baked Milk- and Egg-Allergic Children. *Nutrients* **2021**, *13*, 4540. https:// doi.org/10.3390/nu13124540

Academic Editor: Eva Untersmayr

Received: 18 November 2021 Accepted: 16 December 2021 Published: 18 December 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

"information on the possible and unintentional presence in food of substances or products causing allergies or intolerances, provided voluntarily by the food business operator" [3].

PAL may further reduce the possible food choices of consumers who are already forced to reduce their options [4]. Conversely, PAL-free foods may contain significant amounts of food allergens introduced by contamination at some point in the preparation chain [5]. To discipline PAL, several organisms propose the adoption of a risk-based approach [6]. According to the Voluntary Incidental Trace Allergen Labelling (VITAL) system, a voluntary scheme developed by the Australian and New Zealand food industries [7], food industry may choose to renounce to precautionary statement (action level one) when a food allergen contamination is unlikely, or to include the statement ' . . . . may be present' (action level two) depending on the circumstances. The VITAL reference doses for specific food allergens are derived from diagnostic Oral Food Challenges (OFCs) in populations of patients with food allergy. For a biscuit that may contain egg and/or milk, action level one is suggested at a reference dose of 0.2 mg total protein. For a reasonable portion size of 50 g of biscuits, this translates in a suggested exemption from PAL when the concentration is of 4 mg total protein/kg or less [8,9].

As threshold doses have been not calibrated on a population of patients with severe food allergy, but on the entire population of food allergy sufferers, the risk thresholds may be over-evaluated [10]. Although only a part of the milk/egg allergic patients are also reactive to baked foods [11], the current thresholds were derived from OFCs without distinction among baked-tolerant and baked-allergic patients. Those allergic to baked forms are considered the most reactive portion of the milk/egg allergic population [12], but their thresholds have been only rarely compared to those of milk/egg allergic patients tolerant to baked foods [13].

In this scenario, studies on the effective clinical relevance of smaller doses than the VITAL thresholds in patients extremely allergic to milk and egg are lacking. For this reason, we wanted to evaluate in a group of baked egg- and/or baked milk-allergic patients the tolerance of a baked product labelled as 'may content little amounts of milk and egg'. A secondary objective of our study was to verify the protein quantity of milk and egg in the product using different analytical methods, in order to establish the relationship between quantities traceable below the 1% threshold and the possible development of symptoms.

Finally, this study offers us the opportunity to evaluate the threshold of reactivity to milk- and egg-baked proteins in children severely allergic to these foods.
