Comparison of international food allergen labeling regulations

Food allergy is a significant public health issue worldwide. Regulatory risk management strategies for allergic consumers have focused on providing information about the presence of food allergens through label declarations. A number of countries and regulatory bodies have recognized the importance of providing this information by enacting laws, regulations or standards for food allergen labeling of “priority allergens”. However, different governments and organizations have taken different approaches to identifying these “priority allergens” and to designing labeling declaration regulatory frameworks. The increasing volume of the international food trade suggests that there would be value in supporting sensitive consumers by harmonizing (to the extent possible) these regulatory frameworks. As a first step toward this goal, an inventory of allergen labeling regulations was assembled and analyzed to identify commonalities, differences, and future needs.     

Criteria for identifying allergenic foods of public health importance

The World Health Organisation and other food safety authorities recognise food allergy as a significant public health concern due to the high prevalence and potential severity of the condition and the impact it has on the quality of life and economy. A public health perspective focuses on risk management at the societal level rather than precautions taken by individuals. Allergen lists were originally drawn up on the basis of a combination of prevalence and severity information, but data to document inclusion were limited. Since then the number of allergenic foods for which reactions have been well documented has grown considerably. Yet, most of them are of limited significance to public health. To address food allergy issues from the point of view of risk management, an expert group appointed by the Food Allergy Task Force of the International Life Sciences Institute ILSI Europe reviewed the criteria. We propose a revised set of criteria together with a framework which can be used to help decide which allergenic foods are of sufficient public health importance to be included in allergen lists. Criteria include clinical issues (diagnosis, potency of allergen, severity of reactions), population elements (prevalence, exposure) and modulating factors (food processing). In the framework, data providing evidence for these criteria are weighted according to quality, using a ranking derived from evidence-based medicine. The advantage of this approach is that it makes explicit each of the considerations, thereby rendering the whole process more transparent for all stakeholders.     

Evaluating the effect of food processing on the potential human allergenicity of novel proteins: international workshop report.

The ILSI Health and Environmental Sciences Institute Protein Allergenicity Technical Committee organized an international workshop in June 2006 in Estoril, Portugal, co-sponsored by the ILSI Research Foundation, ILSI International Food Biotechnology Committee and ILSI Europe. The objective was to discuss the effects of food processing on the allergenic potential of proteins and foods. The impact of food processing on the sensitization/induction phases of food allergy, and the bioavailability of allergens to the immune system were presented. Studies evaluating the stability, digestibility, and allergenicity of processed food allergens were identified, and their complexity and limitations discussed. Participants agreed that investigating food allergy mechanisms, validating appropriate methods for identifying allergenic proteins, and refining strategies to assess and manage the risks from food allergy were important before processing considerations are integrated into public-health decision-making for novel proteins. Other factors may also play a role in food allergy and include: food matrix; multiplicity of epitopes; geographic variation in patterns/prevalence of food allergies; and genetic factors, but required further exploration. Food processing may increase or decrease the intrinsic allergenicity of a protein, but current data do not facilitate the identification of specific variables that could be used to reliably determine how processing will influence protein allergenicity.     

Lack of cross-reactivity between the Bacillus thuringiensis derived protein Cry1F in maize grain and dust mite Der p7 protein with human sera positive for Der p7-IgE

Cry1F protein, derived from Bacillus thuringiensis, is effective at controlling lepidopteran pests and a synthetic Cry1F transgene was transferred into maize. For the safety assessment of genetically modified food crops, the allergenic potential of the introduced novel trait(s) is evaluated. Because no single parameter is currently predictive of allergic potential, a 'weight of evidence' approach has been proposed. As part of this assessment, the amino acid (aa) sequence of the Cry1F protein was compared to a database of known allergens using recommended criteria. The Cry1F protein did not show significant similarity or a match of eight contiguous identical aa with any allergen. However, a single six contiguous aa match was identified between Cry1F and the Der p7 protein of the dust mite, Dermatophagoides pteronyssinus. To investigate whether Cry1F was cross-reactive with Der p7, sera from 10 dust mite allergic patients containing Der p 7-specific IgE antibody were used to compare IgE-specific binding. No evidence of cross-reactivity was observed between Cry1F and Der p7. This study provides in vitro IgE sera screening data, that when considered in the context of other bioinformatic data [Hileman R.E., Silvanovich, A., Goodman R.E., Rice E.A., Holleschak G., Astwood J.D., Hefle S.L., 2002. Bioinformatic methods for allergenicity assessment using a comprehensive allergen database. Int. Arch. Allergy Immunol. 128, 280-291; Stadler, M.B., Stadler, B.M., 2003. Allergenicity prediction by protein sequence. FASEB J. 17, 1141-1143.], adds further evidence arguing against the use of a six contiguous identical amino acid search to identify potential cross-reactive allergens. Cry1F is heat labile, rapidly hydrolyzed in an in vitro pepsin resistance assay, not glycosylated and not from an allergenic source. Taken together, these data indicate a lack of allergenic concern for Cry1F.     

Morphological and biochemical correlates of chemical induced injury in the lung

We have reviewed some of the factors which contribute to lung damage by various toxicants. These include disposition of the chemical, its metabolism, individual cell type susceptibility and the potential for the tissue to repair. We have discussed the use of biochemical parameters to measure the functional activity of individual cell types in order to predict the damage to specific cell types and concluded that careful morphological analysis of lung tissue is likely to provide a more sensitive and informative measure of specific cell type injury. However, in order to investigate the mechanism of toxicity of pulmonary toxicants it is essential to establish the primary biochemical event that leads to cell damage and morphological change. The importance of separating the relevant biochemical change(s) from the cascade of biochemical events associated with dead and dying cells and the reparative response of the lung is emphasised.This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundation's Standing Committee for the European Medical Research Councils and held at the Medical Research Council Toxicology Unit, Carshalton, U. K. Those taking part were: W. N. Aldridge (AST; as above); J. Bignon (Unit for Research in Renal and Pulmonary Pathology, University of Paris, Creteil, France); P. H. Burri (Section of Developmental Biology, Institute of Anatomy, University of Berne, Switzerland); G. M. Cohen (as above); D. Dinsdale (MRC Toxicology Unit, Carshalton U. K.); P. Hedqvist (Dept. of Physiology, Karolinska Institute, Stockholm, Sweden); D. Henschler (AST; Dept. of Toxicology and Pharmacology, University of Wurzburg, FDR); G. J. Laurent (Biochemistry Unit, Cardiothoracic Institute, University of London, London, U. K.); R. Lauwerys (AST Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (AST; Poison Control Centre, Lyon, France); P. Moldeus (Dept. of Forensic Medicine, Karolinska Institute, Stockholm, Sweden); B. Nemery (MRC Toxicology Unit, Carshalton, U. K.); A. Saria (Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); L. L. Smith (as above);B. Terracini (AST; Dept. of Pathology and Cancer Epidemiology, University of Turin, Italy)     

Under the conditions of intended use – New developments in the FEMA GRAS program and the safety assessment of flavor ingredients

In 1995 we published a review describing the scientific and legal bases for the GRAS assessment program for flavor ingredients sponsored by the Flavor and Extract Manufacturers Association of the United States (FEMA) [Hallagan, J.B., Hall, R.L., 1995. FEMA GRAS – A GRAS assessment program for flavor ingredients. Regulatory Toxicology and Pharmacology 21, 422]. This review provides new information related to flavor safety assessment and regulation and is intended to complement our previous report. The FEMA GRAS assessment program is the most extensive and longest running industry-sponsored GRAS program and has established a sound record of scientific rigor and transparency. In this review, in addition to providing general information on the topics of flavor safety assessment and regulation, we explore the effects of recent developments on the four pillars of the FEMA GRAS assessment program: (1) general recognition; (2) among experts qualified by scientific training and experience to evaluate safety; (3) through scientific procedures; (4) under the conditions of intended use in food. We conclude that developments since our last review in 1995 have further strengthened the FEMA GRAS assessment program allowing it to maintain its global leadership role in the safety assessment of flavor ingredients.     

Approaches to risk assessment in food allergy: Report from a workshop ‘‘developing a framework for assessing the risk from allergenic foods”

A workshop was organised to investigate whether risk assessment strategies and methodologies used in classical/conventional toxicology may be used for risk assessment of allergenic foods, to discuss the advantages and limitations of different approaches and to determine the research needed to move the area forward. Three possible approaches to safety assessment and risk assessment for allergenic foods were presented and discussed: safety assessment using NOAEL/LOAEL and uncertainty factors, safety assessment using Benchmark Dose and Margin of Exposure (MoE), and risk assessment using probabilistic models.     

Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by quality-control failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen expressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.     

A risk-based classification scheme for genetically modified foods. I: Conceptual development

The predominant paradigm for the premarket assessment of genetically modified (GM) foods reflects heightened public concern by focusing on foods modified by recombinant deoxyribonucleic acid (rDNA) techniques, while foods modified by other methods of genetic modification are generally not assessed for safety. To determine whether a GM product requires less or more regulatory oversight and testing, we developed and evaluated a risk-based classification scheme (RBCS) for crop-derived GM foods. The results of this research are presented in three papers. This paper describes the conceptual development of the proposed RBCS that focuses on two categories of adverse health effects: (1) toxic and antinutritional effects, and (2) allergenic effects. The factors that may affect the level of potential health risks of GM foods are identified. For each factor identified, criteria for differentiating health risk potential are developed. The extent to which a GM food satisfies applicable criteria for each factor is rated separately. A concern level for each category of health effects is then determined by aggregating the ratings for the factors using predetermined aggregation rules. An overview of the proposed scheme is presented, as well as the application of the scheme to a hypothetical GM food.     

A risk-based classification scheme for genetically modified foods I: Conceptual development

The predominant paradigm for the premarket assessment of genetically modified (GM) foods reflects heightened public concern by focusing on foods modified by recombinant deoxyribonucleic acid (rDNA) techniques, while foods modified by other methods of genetic modification are generally not assessed for safety. To determine whether a GM product requires less or more regulatory oversight and testing, we developed and evaluated a risk-based classification scheme (RBCS) for crop-derived GM foods. The results of this research are presented in three papers. This paper describes the conceptual development of the proposed RBCS that focuses on two categories of adverse health effects: (1) toxic and antinutritional effects, and (2) allergenic effects. The factors that may affect the level of potential health risks of GM foods are identified. For each factor identified, criteria for differentiating health risk potential are developed. The extent to which a GM food satisfies applicable criteria for each factor is rated separately. A concern level for each category of health effects is then determined by aggregating the ratings for the factors using predetermined aggregation rules. An overview of the proposed scheme is presented, as well as the application of the scheme to a hypothetical GM food.     

In silico assessment of the potential allergenicity of transgenes used for the development of GM food crops

Genetically modified (GM) crops require allergenicity and toxicity assessment of the novel protein(s) to ensure complete safety to the consumers. These assessments are performed in accordance with the guidelines proposed by Codex (2003) and ICMR (2008). The guidelines recommend sequence homology analysis as a preliminary step towards allergenicity prediction, later in vitro experiments may be performed to confirm allergenicity. In the present study, an in silico approach is employed to evaluate the allergenic potential of six transgenes routinely used for the development of GM food crops. Among the genes studied, manganese superoxide dismutase (MnSOD) and osmotin shares greater than 90% identity with Hev b 10 and Cap a 1w, respectively. Chitinase shares greater than 70% identity with allergens namely Pers a 1 and Hev b 11, and fungal chitinase showed significant IgE binding with 7 of 75 patients’ sera positive to different food extracts. Glucanases (alfalfa, wheat) and glycine betaine aldehyde dehydrogenase gene share 50% homology with allergens like – Ole e 9, Cla h 10 and Alt a 10. The results demonstrate the allergenic potential of six genes and can serve as a guide for selection of transgenes to develop GM crops.     

Interpreting the biological relevance of bioinformatic analyses with T-DNA sequence for protein allergenicity

Global regulatory agencies require bioinformatic sequence analysis as part of their safety evaluation for transgenic crops. Analysis typically focuses on encoded proteins and adjacent endogenous flanking sequences. Recently, regulatory expectations have expanded to include all reading frames of the inserted DNA. The intent is to provide biologically relevant results that can be used in the overall assessment of safety. This paper evaluates the relevance of assessing the allergenic potential of all DNA reading frames found in common food genes using methods considered for the analysis of T-DNA sequences used in transgenic crops. FASTA and BLASTX algorithms were used to compare genes from maize, rice, soybean, cucumber, melon, watermelon, and tomato using international regulatory guidance. Results show that BLASTX for maize yielded 7254 alignments that exceeded allergen similarity thresholds and 210,772 alignments that matched eight or more consecutive amino acids with an allergen; other crops produced similar results. This analysis suggests that each nontransgenic crop has a much greater potential for allergenic risk than what has been observed clinically. We demonstrate that a meaningful safety assessment is unlikely to be provided by using methods with inherently high frequencies of false positive alignments when broadly applied to all reading frames of DNA sequence.     

我国公众对保健食品广告认知状况的调查分析

目的:了解公众对保健食品、保健食品广告以及广告监管规定的认知状况,为全面研究和分析保健食品广告现状提供参考。方法 :对普通消费者、媒体人员、行业企业人员、相关政府部门以问卷调查、开座谈会、深度访谈的形式进行调查,并对结果进行统计分析。结果与结论:普通消费者对保健食品的概念及保健食品广告的认知度普遍较低,不能识别违法保健食品广告,需要引导和教育;行业企业人员认为广告是推介产品的重要渠道,违法保健食品广告破坏了保健食品市场秩序;媒体需要摒弃个人利益,承担起社会责任,不刊播未经审批的保健食品广告;监管部门要依法行政,严把审查关口和尺度,对违法保健食品广告惩处到位。     

The application of post-market monitoring to novel foods.

The role of post-market monitoring (PMM) in the safety assessment of novel foods is critically discussed in order to derive guidelines as to in which situations the application of PMM might be warranted. Available data sources on food consumption and health status, and the methodologies for generating such data are reviewed. The paper suggests improvements to make them more applicable for PMM purposes. It is concluded that any PMM programme must be a hypothesis-driven scientific exercise. PMM can have a role as a complement to, but not as a replacement for, a comprehensive pre-market safety assessment. Its use may be appropriate to confirm that product use is as predicted in the pre-market assessment; to provide reassurance that effects observed in the pre-market assessment occur with no greater frequency or intensity in the post-market phase than anticipated; and to investigate the significance of any adverse effects reported by consumers after market-launch. However PMM is insufficiently powerful to test the hypothesis that any effects seen in the pre-market assessment are absent in the post-market phase. Current methodologies place limitations on what PMM can achieve. PMM should only be used when triggered by or when the focus is on specific evidence-based questions.     

天津地区食物过敏患者sIgG检测结果分析

目的:了解天津地区过敏患者血清食物过敏原特异性IgG(sIgG)的表达情况,探讨食物不耐受与过敏性皮肤病的关系。方法:应用酶联免疫吸附试验(ELISA)对834例疑似食物变态反应性疾病患者血清中食物过敏原的sIgG抗体进行检测,分析食物过敏原种类特点。结果:834例患者中有638例有1~11种不等的食物过敏原sIgG升高,总阳性率为76.5%,其中存在1~2种食物不耐受的比例最高(58.1%)。在14种食物中,食物过敏原sIgG升高以鸡蛋(51.9%)最多见,其次分别是蟹(21.6%)、虾(19.3%)、牛奶(16.5%),猪肉sIgG阳性率(0.5%)最低。另外,≤14岁患者与>14岁患者对鸡蛋、牛奶、蟹、虾、小麦、西红柿过敏情况差异有统计学意义(均P<0.01)。241例皮肤病患者中有171例食物过敏原检测结果呈阳性,阳性反应率为71.0%。结论:鸡蛋、甲壳类(蟹、虾)、牛奶是食物变态反应性疾病的主要过敏原。食物过敏或食物不耐受的症状与皮肤过敏性疾病关系密切。     

Development of a Testing Battery to Assess Chemical-Induced Immunotoxicity: National Toxicology Program's Guidelines for Immunotoxicity Evaluation in Mice

Development of a Testing Battery to Assess Chemical-InducedImmunotoxicity: National Toxicology Program's Guidelines forImmunotoxicity Evaluation in Mice. Luster, M. I., Munson, A.E., Thomas, P. T., Holsapple, M. P., Fenters, J. D., White,K. L., Jr., Lauer, L. D., Germolec, D. R., Rosenthal, G. J.,and Dean, J. H. (1988). Fundam. Appl. Toxicol..     

State of the art in benefit-risk analysis: Food microbiology

Over the past years benefit-risk analysis (BRA) in relation to foods and food ingredients has gained much attention; in Europe and worldwide. BRA relating to food microbiology is however a relatively new field of research. Microbiological risk assessment is well defined but assessment of microbial benefits and the weighing of benefits and risk has not been systematically addressed. In this paper the state of the art in benefit-risk analysis in food microbiology is presented, with a brief overview of microbiological food safety practices.The quality and safety of foods is commonly best preserved by delaying the growth of spoilage bacteria and contamination by bacterial pathogens. However, microorganisms in food can be both harmful and beneficial. Many microorganisms are integral to various food production processes e.g. the production of beer, wine and various dairy products. Moreover, the use of some microorganisms in the production of fermented foods are often claimed to have beneficial effects on food nutrition and consumer health. Furthermore, food safety interventions leading to reduced public exposure to foodborne pathogens can be regarded as benefits. The BRA approach integrates an independent assessment of both risks and benefits and weighs the two using a common currency.Recently, a number of initiatives have been launched in the field of food and nutrition to address the formulation of the benefit-risk assessment approach. BRA has recently been advocated by EFSA for the public health management of food and food ingredients; as beneficial and adverse chemicals can often be found within the same foods and even the same ingredients. These recent developments in the scoping of BRA could be very relevant for food microbiological issues. BRA could become a valuable methodology to support evaluations and decision making regarding microbiological food safety and public health, supplementing other presently available policy making and administrative tools for microbiological food safety management.     

Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment.

An animal model for food allergy is needed to assess genetically modified food crops for potential allergenicity. The ideal model must produce allergic antibody (IgE) to proteins differentially according to known allergenicity before being used to accurately identify potential allergens among novel proteins. The oral route is the most relevant for exposure to food antigens, and a protein's stability to digestion is a current risk assessment tool based on this natural route. However, normal laboratory animals do not mount allergic responses to proteins administered orally due to oral tolerance, an immunologic mechanism which specifically suppresses IgE. To circumvent oral tolerance and evoke differential IgE responses to a panel of allergenic and nonallergenic food extracts, female C3H/HeJ mice were exposed subcutaneously or orally with cholera toxin as an adjuvant. All foods elicited IgE by the subcutaneous route. Oral exposure, however, resulted in IgE to allergens (peanut, Brazil nut, and egg white) but not to nonallergens (spinach and turkey), provided that the dose and exposures were limited. Additionally, in vitro digestibility assays demonstrated the presence of digestion-stable proteins in the allergenic food extracts but not in the nonallergenic foods. Our results suggest that the subcutaneous route is inadequate to distinguish allergens from nonallergens, but oral exposure under the appropriate experimental conditions will result in differential allergic responses in accordance with known allergenicity. Moreover, those foods containing digestion-resistant proteins provoke allergic responses in this model, supporting the current use of pepsin resistance in the decision tree for potential allergenicity assessment.