Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins

The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity. In this paper we review the potential of current methodologies (in silico, in vitro degradation, in vitro IgE binding, animal models and clinical studies) to address these outcomes for risk assessment purposes for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish between proteins of high and low allergenicity, which can then be applied to assess new proteins with unknown risks. © 2017 The Authors Chemicals/CAS: immunoglobulin E, 37341-29-

Threshold dose for peanut: Risk characterization based upon diagnostic oral challenge of a series of 286 peanut-allergic individuals

Clinical records of 286 consecutive patients reacting positively with objective symptoms to double-blind, placebo-controlled oral peanut challenges at University Hospital, Nancy, France were examined for individual No Observed Adverse Effect Levels (NOAELs) and Lowest Observed Adverse Effect Levels (LOAELs). After fitting to a log-normal probability distribution model, the ED10 and ED05 were 14.4 and 7.3 mg (expressed as whole peanut), respectively, with 95% lower confidence intervals of 10.7 and 5.2 mg, respectively. Compared to results from a previous study where the ED10 was based upon individual peanut thresholds gleaned from 12 publications, a statistically significant difference was observed between the ED50’s, but not the ED10’s of the two probability distribution curves. The Nancy patient group contains more sensitive subjects than the group from the published literature thus contributing to the observed differences. Minimum eliciting dose-distributions for patients with histories of more severe reactions (grade 4 or 5; 40 subjects) did not differ significantly from those of patients with histories of less severe reactions (grades 1–3; 123 subjects). These data and this modeling approach could be used to establish population thresholds for peanut-allergic consumers and thereby provide a sound basis for allergen control measures in the food industry

From Hazard to Risk:Assessing the Risk

Regulatory thresholds for allergenic foods have not yet been developed. This means that public and industrial risk managers do not have regulatory thresholds to decide if a content or level of contamination is acceptable or not. For a long time, data have been inadequate to define safe thresholds for food allergens. More and more challenge data from food allergic patients are now available, and this opens the possibility to perform more advanced food allergy safety and risk assessments. These can be used to inform risk management decisions and ultimately to form the basis for regulatory thresholds. In the chapter we describe three different approaches for safety/risk assessment based on no/low observed adverse effect level, benchmark dose, or probabilistic modeling. These methods are illustrated by examples from real life and the possibilities and limitations are discussed. © 2014 Elsevier Inc. All rights reserved

Establishment of Reference Doses for residues of allergenic foods: report of the VITAL Expert Panel.

In 2011, an expert panel was assembled to establish appropriate Reference Doses for allergenic food residues as a part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program of The Allergen Bureau of Australia & New Zealand (ABA). These Reference Doses would guide advisory labeling decisions for use on food labels. Individual NOAELs and LOAELs were obtained from clinical challenges of food-allergic subjects. Statistical dose-distribution models (log-normal, log-logistic, Weibull) were applied to the individual NOAELs and LOAELs for each allergenic food. The Reference Doses, in terms of mg of total protein from the allergenic food, were based upon either the ED01 (for peanut, cow's milk), the 95% lower confidence interval of the ED05 (for wheat, soybean, cashew, shrimp, sesame seed, mustard, and lupine), or both (egg, hazelnut) using all appropriate statistical dose-distribution models. Reference Doses were established for 11 allergenic foods ranging from 0.03mg for egg protein to 10mg for shrimp protein. Reference Doses were not established for fish or celery due to poor model fits with existing data. Reference Doses were not established for other tree nuts beyond hazelnut and cashew because of the absence of data on NOAELs and LOAELs from individual subjects. © 2013 Elsevier Ltd

Allergen reference doses for precautionary labeling (VITAL 2.0): clinical implications.

Background There has been a dramatic proliferation of precautionary labeling by manufacturers to mitigate the perceived risk from low-level contamination from allergens in food. This has resulted in a significant reduction in choice of potentially safe foods for allergic consumers. Objectives We aimed to establish reference doses for 11 commonly allergenic foods to guide a rational approach by manufacturers based on all publically available valid oral food challenge data. Methods Reference doses were developed from statistical dose-distribution modeling of individual thresholds of patients in a dataset of more than 55 studies of clinical oral food challenges. Sufficient valid data were available for peanut, milk, egg, and hazelnut to allow assessment of the representativeness of the data used. Results The data were not significantly affected by the heterogeneity of the study methodology, including little effect of age on results for those foods for which sufficient numbers of adult challenge data were available (peanut and hazelnut). Thus by combining data from all studies, the eliciting dose for an allergic reaction in 1% of the population estimated for the following were 0.2 mg of protein for peanut, 0.1 mg for cow's milk, 0.03 mg for egg, and 0.1 mg for hazelnut. Conclusions These reference doses will form the basis of the revised Voluntary Incidental Trace Allergen Labeling (VITAL) 2.0 thresholds now recommended in Australia. These new levels will enable manufacturers to apply credible precautionary labeling and provide increased consumer confidence in their validity and reliability, as well as improving consumer safety. © 2013 American Academy of Allergy, Asthma & Immunology