W. Marty Blom

TNO | tno · Expertise Group for Risk Analysis for Products In Development (RAPID)

For most allergenic foods, limited availability of threshold dose information within the population restricts the advice on action levels of unintended allergenic foods which should trigger advisory labelling on packaged foods. The objective of this paper is to provide guidance for selecting an optimal sample size for threshold dosing studies for m...

Background Soybean and peanut, members of the Legume family, are recognized as common allergenic foods by the FAO Codex Alimentarius. EU directive 2003/89/EC and US Food Allergen Labeling and Consumer Protection Act prescribe labelling of food products for these two major allergenic foods. EU directive 2007/68/EC requires labelling for lupin, anoth...

Background Children with cow’s milk allergy (CMA) need a cow’s milk protein (CMP) free diet to prevent allergic reactions. For this, reliable allergy-information on the label of food products is essential to avoid products containing the allergen. On the other hand, both overzealous labeling and misdiagnosis that result in unnecessary elimination d...

Background: For most allergenic foods, insufficient threshold dose information within the population restricts the advice on levels of unintended allergenic foods which should trigger precautionary labeling on prepackaged foods. Objective: We wanted to derive threshold dose distributions for major allergenic foods and to elaborate the protein do...

Background Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. Methods All sesame oral food challenges (OFCs), perfo...

Lack of guidance regarding selection of food intake values for allergen risk assessment can lead to different outcomes for similar levels of allergens in food products. Several food consumption survey databases (United States, North-West Europe, and Netherlands) were analyzed to identify optimal food intake percentiles using a sensitivity analysis....

Food allergy has been recognized already in early history as a condition triggered in some individuals upon consumptions of specific foods. However, its recognition as an essential element to be addressed in food safety management is of much more recent date. As a consequence, risk assessment and risk management practices for food allergy are less...

While there are EU laws for priority allergenic ingredients information on food product packaging, there is no legislation about Precautionary Allergen Labelling (PAL) for unintended allergen presence (UAP). As a result, PAL is used in different ways by different manufacturers and retailers, which hampers consumers’ interpretation of the informatio...

Access to Eliciting Doses (ED) for allergens enables advanced food allergen risk assessment. Previously, the full ED range for 14 allergenic foods, including milk, and recommendations for their use were provided (Houben et al., 2020). Additional food challenge studies with cow's milk-allergic patients added 247 data points to the original dataset....

Background: Cow's milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low-level CM exposure, as well as the reproducibility of reaction thresholds. Objective: We undertook an individual participant data (IPD) meta-analysis of studies reporting double-blind, pla...

Quantitative risk assessment (QRA) for allergens exists in many different forms with different requirements placed on the risk assessor depending on the question that needs to be answered. An electronic workshop held in October 2020 and comprising representatives from a wide range of food allergy and allergen stakeholder groups identified that a su...

Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) which are frequently ignored by fo...

Background: Understanding consumers' interpretation of allergy information is crucial for effective food safety policies. We evaluated consumer understanding of allergy information on foods in controlled, experimental studies. Method: Using 18 packaged foods, we evaluated consumer understanding of information about allergens in two experiments:...

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 Do...

The prevalence of IgE‐mediated food allergy diagnosed by clinical history and positive serology in adults across Europe ranges from 0.3‐6% (1). Almost half of the food allergic adults are confronted with accidental allergic reactions yearly (2). Especially moderate and severe reactions require medical consultation and treatment, which can have a hi...

Background Eliciting doses (e.g. ED01 or ED05 values, the amount of allergen expected to cause objective symptoms in 1% and 5% of the allergic population) are increasingly used to inform allergen labelling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis to these low levels of allergen exposu...

National population-based food consumption surveys are used in food allergen risk assessment. It would be beneficial if food intake data is interchangeable between countries to bridge potential gaps present in national survey data, which is only possible when risk assessment outcomes for comparable food product groups between countries are fairly s...

Background Allergen information on product labels is crucial in food allergy management. Though, inadequacy in current labelling practices are one of the major causes for accidental reactions upon consuming prepacked food products. Objective This study analyses current status of communicating allergen information on food labels and provides practi...

Previously, we published selected Eliciting Dose (ED) values (i.e. ED01 and ED05 values) for 14 allergenic foods, predicted to elicit objective allergic symptoms in 1% and 5%, respectively, of the allergic population (Remington et al., 2020). These ED01 and ED05 values were specifically presented and discussed in the context of establishing Referen...

Allergenic food particles (typically ∼0.5-5 mm) may unintentionally end up in food products during production and can pose a risk for the allergic consumer. A single particle can provoke allergic symptoms in an allergic consumer when the dose of allergenic protein exceeds minimal eliciting doses. However, there is a lack of fundamental knowledge an...

Unintentional intake of allergens through food products poses a daily risk for allergic patients. Models estimating the risk of reactions mostly use intake data from general population surveys. Our study evaluates the comparability of food intake levels in the general population to those in the food allergic population. Data were collected by a 24-...

Background Allergic reactions to meals consumed outside the home are common, can be severe and sometimes fatal. Objective To quantify the risk reduction potentially achieved by increasing an individual’s threshold sensitivity to peanut (such as via immunotherapy) in scenarios of peanut exposure through shared kitchen materials in a restaurant sett...

Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were p...

Background: Food allergies are a significant public health issue, and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility of limiting risks to zero, quantitative allergen risk assessment and management strategies are needed. Objective: We sought...

Food allergy is a major public health concern with avoidance of the trigger food(s) being central to management by the patient. Food information legislation mandates the declaration of allergenic ingredients; however, the labelling of the unintentional presence of allergens is less defined. Precautionary allergen labelling (PAL) was introduced by t...

One of the input parameters in food allergy risk assessment is the amount of a given food consumed at an eating occasion. There is no consensus on how to use food consumption data when assessing the risk from unintended allergen presence in food products. A sensitivity analysis was performed to establish the optimal food consumption estimate for a...

Many food innovations rely on the introduction and use of new or modified proteins. New or modified food proteins may lead to major health risks due to their inherent potential to cause food allergy. Currently, the pre-market allergenicity assessment for new or modified food proteins and protein sources relies on methods for identifying allergenic...

Background Cofactors, like physical exercise and alcohol intake, might be associated with the severity or occurrence of food allergic reactions. Objective To gain insight into the frequency of presence of potential cofactors in accidental food allergic reactions in adults and to what extent these factors influence the severity and occurrence of al...

Background: Accidental allergic reactions to food are frequent, can be severe and even fatal. Objective: To analyze the culprit food products and levels of unexpected allergens in accidental reactions. Methods: A prospective cohort study was conducted in adults (n=157) with a physician-confirmed diagnosed food allergy. During a 1-year follow u...

Background The role of sensitization to commercially available allergens of English walnut (Juglans regia) Jug r 1, 2 and 3 in walnut allergy has been previously investigated in walnut allergic adults and was unable to explain allcases of walnut allergy. Objectives Identify recognized walnut allergens, other than the ones previously investigated (...

Background: Nut allergy varies from pollen cross-allergy, to primary severe allergy with life-threatening symptoms. The screening of IgE antibodies to a wide spectrum of allergens, including species-specific and cross-reactive allergens, is made possible via microarray analysis. Objective: We sought to study the association of variable IgE sensi...

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 clin...

Refined vegetable oils including refined peanut oil are widely used in foods. Due to shared production processes, refined non-peanut vegetable oils can contain residual peanut proteins. We estimated the predicted number of allergic reactions to residual peanut proteins using probabilistic risk assessment applied to several scenarios involving food...

Background: In food allergy, eliciting doses (EDs) of foods on a population level can improve risk management and labeling strategies for the food industry and regulatory authorities. Previously, data available for walnut were unsuitable to determine EDs. Objective: The objective of this study was to determine EDs for walnut allergic adults and...

Specific IgE to walnut 2S albumin Jug r 1 was superior compared to Jug r 2 and 3 in diagnosing walnut allergy in adults, but did not have additional value compared to sIgE to walnut extract or SPT with commercial walnut extract.

Introduction Involvement of cofactors, like physical exercise, alcohol consumption and use of several types of medication, are associated with more severe food allergic symptoms. However, there is limited evidence on how often cofactors play a role in food allergic reactions. The study aimed to get more insight into the frequency of exposure to cof...

To improve food labeling strategies, information regarding eliciting doses (ED) and the effect of patient characteristics on these EDs is necessary. Establish EDs for objective and subjective symptoms and analyze the effect of sensitization levels and other patient characteristics on threshold distribution curves (TDC). Threshold data from 100 adul...

Background Allergens in food may pose a risk to allergic consumers. While there is EU regulation for allergens present as an ingredient, this is not the case for unintended allergen presence (UAP). Food companies use precautionary allergen labels to inform allergic individuals of a potential risk from UAPs. The current study investigates the risk o...

The availability of clinically established DBPCFC minimal eliciting doses determined in food-allergic individuals is increasing and previous work has shown these data can be used to determine population based reference doses for allergen risk management. Despite the large amount of data for peanut, milk, egg and hazelnut, EU and US public health au...

Allergens in food pose a risk to allergic consumers, especially if they are present in food without declaration or warning. While there is EU regulation for allergens present as an ingredient, this is not the case for unintended allergen presence (UAP). Food companies use precautionary “may contain” labels to inform allergic individuals of a potent...

Highly refined peanut oil is considered to pose a risk to people with peanut allergy.[1] Although that risk has not been characterised, but controlled clinical challenges suggest it is negligible. A consequence is that the risk from cross contact between other refined vegetable oils and refined peanut oil during production must be assessed in order...

The " Big 8 " food allergens consists of cow's milk, eggs, wheat, peanuts, tree nuts, soybeans, fish, and crustacean shellfish and account for ~90% of the allergic reactions to foods. During the scientific review of the VITAL ® (Voluntary Incidental Trace Allergen Labelling) program , individual challenge data were gathered for the Big 8 food aller...

Food preferably has to be tasteful, healthy, attractive, and affordable, but should above all be safe. The safety of our daily food nowadays is at a reasonable level, but is far from obvious. During the past half century, food risk assessment and risk management approaches have developed. Yet, several white spots or areas of inefficiency still exis...

Food allergic patients average one unexpected allergic reaction per year. A major cause of reactions is the unintentional presence of allergens in packaged foods as a result of cross contamination during production. Consumers encounter voluntary labeling alerts like "may contain traces of ..." which show a poor correlation with the actual presence...

Natural Killer (NK) cells are important in the first response against viruses and tumours. Compounds that modulate human NK cell activity offer interesting prophylactic and therapeutic options, however, a systematic screening tool is lacking. Development of suitable NK cell lines or receptor-based assays is hindered by the highly complicated regula...

Exposure to compounds in consumer products can be assessed using the computer program ConsExpo (Consumer Exposure). Given the huge number of consumer products, it is not possible to calculate the exposure for each separate product, so a limited number of groups containing similar products are defined. The information for each group of products is d...

The spatio-temporal relationship between a decrease in the mitochondrial membrane potential (MMP) and externalization of phosphatidylserines (PS) during induction of apoptosis was investigated in single freshly isolated hepatocytes. Apoptosis was induced in the hepatocytes in three different ways: attack by activated Natural Killer cells, exposure...

Previously, we showed that interleukin-2 activated Natural Killer cells (A-NK cells) in vitro rapidly induced apoptosis in freshly isolated rat hepatocytes (Blom et al., 1999. Hepatology 29 (3): 785-792) which was caused by a rapid decrease in the mitochondrial membrane potential and activation of caspases. In the present study we investigated the...

Mathematical models are available to assess the exposure of compounds in consumer products. The computer program CONSEXPO (Consumer Exposure) is used for the calculations. Given the huge number of consumer products, it is not possible to define an exposure assessment of every product separately, and a limited number of main categories containing si...

Exposure to and intake of compounds in consumer products are assessed using available mathematical models. Calculations are carried out with the computer program, CONSEXPO (Consumer Exposure). Given the huge number of consumer products, it is not possible to define exposure models and parameter values for each separate product, so a limited number...

Natural Killer cells are immune cells that recognize and eliminate altered and non-self cells from the circulation. To study the interaction between NK cells and target cells, we set up an experimental system consisting of rat Interleukin-2 activated Natural Killer cells (A-NK cells) and rat hepatocytes with a masked Major Histocompatibility Comple...

The mechanism by which cycloheximide induces apoptosis in isolated rat hepatocytes was studied. Cycloheximide (1-300 microM) induced apoptosis within 3-4 hr in the hepatocytes. Specific apoptotic characteristics such as blebbing, phosphatidyl serine (PS) exposure, chromatin condensation, and nuclear fragmentation were induced. Cycloheximide (CHX) d...

The presence and localisation of G-actin in various cell lines was studied using the highly G-actin specific, fluorescence-labelled vitamin D-binding protein. In various cell-types, pig kidney-derived cells (LLC-PK1), Chinese hamster ovary (CHO) cells, SV-40 transformed African green monkey kidney (COS) cells and human hepatoma (HepG2) cells, G-act...

Stressor-induced changes in the cytoskeleton, of which actin is a major component, may lead to apoptosis. The role of drug-induced changes in nuclear G-actin and apoptosis was studied in freshly isolated hepatocytes. Several protein synthesis inhibitors, cycloheximide, puromycin, and emetine, induced 10 to 15% apoptosis in hepatocytes after 4 h, as...

Natural killer (NK) cells play a crucial role in the elimination of virus-infected or transformed cells in the liver. In this article, we describe the mechanism by which liver cells are killed by NK cells. Interleukin-2-activated natural killer (A-NK) cells from the rat induced apoptotic cell death in 30% of freshly isolated rat hepatocytes within...

Extracellular ATP induces bleb formation in isolated rat hepatocytes. We examined the effect of extracellular ATP on the actin cytoskeleton of these hepatocytes. Exposure to 100 microM ATP caused pronounced nuclear accumulation of G-actin. ADP, AMP, adenosine, and dibutyryl-cAMP induced the same effect. Adenosine deaminase could inhibit both ATP- a...

Extracellular ATP is an important trigger of a variety of physiological functions in many cell types. Previous studies have shown that 0.4 mM ATP induces a high intracellular free calcium concentration in isolated rat hepatocytes, eventually causing cell death. Exposure of hepatocytes to a non-cy totoxic extracellular concentration of 0.1 mM ATP4,...

In vivo and in vitro biotransformation of secondary aromatic amines was investigated using 4-fluoro-N-methylaniline as the model compound. Attention was focused on the role of cytochromes P-450 and the flavin-containing monooxygenase in formation of the various metabolic products. In vitro studies using microsomal preparations, purified reconstitut...