According to EU regulation, genetically modified (GM) plants considered to be allergenic have to be assessed concerning their endogenous allergens before placement on the EU market, in line with the international standards described in Codex Alimentarius. Under such premises, a quantitative relevant increase in allergens might occur in GM plants as an unintended effect compared with conventionally produced crops, which could pose a risk to consumers. Currently, data showing a connection between dose and allergic sensitisation are scarce since the pathophysiological mechanisms of sensitisation are insufficiently understood. In contrast, data on population dose-distribution relationships acquired by oral food challenge are available showing a connection between quantity of allergenic protein consumed and the population of allergic individuals experiencing reactions. Soybean is currently the only recognised allergenic GM food by law for which EFSA has received applications and was therefore taken as an example for defining an assessment strategy. Identification of potential allergens, methodology for quantification as well as risk assessment considerations, are discussed. A strategy is proposed for the identification, assessment and evaluation of potential hazards/risks concerning endogenous allergenicity in food derived from plants developed by biotechnology. This approach could be expanded to other allergenic foods in the future, whenever required.

The genetically modified (GM) maize event MON810 has been inserted with a processed version of the transgene, cry1Ab, derived from the soil bacterium Bacillus thuringiensis (Bt) to express proteins with insecticidal properties. Such proteins may introduce new allergens and also act as adjuvants that promote allergic responses. While focus has been on safe consumption and hence the oral exposure to GM food and feed, little is known regarding inhalation of pollen and desiccated airborne plant material from GM crops. The aim of this study was to investigate whether plant material from the Cry1Ab‐expressing maize variety MON810, or trypsin‐activated Cry1Ab (trypCry1Ab) protein produced in recombinant bacteria, may act as adjuvants against the allergen ovalbumin (OVA) in a mouse model of airway allergy. A clear proallergic adjuvant effect of the mucosal adjuvant cholera toxin (CT) was demonstrated, determined as increased specific IgE, eosinophils and Th2 cytokines in MLN cell supernates, while no elevation in OVA‐specific antibodies or cytokine release from MLN cells after stimulation with OVA were observed in mice receiving Cry1Ab‐containing plant materials or the trypCry1Ab protein. Our data suggest that Cry1Ab proteins had no detectable systemic adjuvant effect in mice after airway exposure. Further experiments with purified plant proteins, as well as long‐term exposures needs be conducted to further evaluate exposures experienced in real‐life situations.

Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured.

Immunisation of female mice with the allergen ovalbumin (OVA) during pregnancy reduces the OVA-specific IgE response in adult offspring. To approach primary prevention strategies for allergy, we investigated to what extent genetic, paternal and maternal factors influence this suppressive effect on allergic sensitisation in offspring and investigated the possibility of pregestational immunisation. Maternal allergen immunisation reduced OVA-specific IgE levels in immunised offspring, even after maternal immunisation up to 8 weeks before conception without further allergen exposure. Immunisation of immunodeficient BALB/c severe combined immune deficiency (SCID) dams mated with wild type males did not lead to IgE suppression in offspring, indicating the importance of a functional maternal immune system. Immunisation of male mice before the relevant spermatogenesis did not cause antibody suppression in offspring. OVA-specific IgG1, presumably of maternal origin, was present in naïve offspring only from immunised dams and was associated with suppressed IgE responses after offspring immunisation. The IgE-suppressive effect of maternal immunisation was demonstrated in all three immunocompetent strains tested (NIH/OlaHsd, BALB/cA and C57BL/6 mice). In conclusion, suppression of allergen-specific IgE production in offspring could not be induced by paternal immunisation, and genetic factors were of minor importance. In contrast, we demonstrate the necessity of maternal factors, possibly allergen-specific IgG1, resulting from a functional adaptive immune response, for the IgE-suppressive effect in offspring. These maternal factors could be induced by immunisation of female mice even before conception.

Background According to EU legislation, genetically modified plants (GM plants) should follow a scientific assessment of any risk that they may pose to human and animal health, including an allergenicity assessment. According to the EFSA guidance, the allergenicity assessment of GM plants is structured into the assessment of i) the newly expressed proteins and ii) the whole GM plant. For the latter and as a part of the assessment, if the GM plant receiving the introduced gene(s) is known to be allergenic, its endogenous allergenicity is compared with that of its non-GM comparator(s).

SummaryBackgroundSensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment.ObjectiveThe objective of this study was firstly to describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13‐year‐old adolescents and secondly to identify home characteristics associated with the presence of food allergen contamination in dust.MethodsFood allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analysed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models.ResultsFish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (< 100 m2) than larger dwellings (≥ 130 m2); 63–71% of the small dwellings (n = 24) had milk, peanut, and fish allergens in the samples compared with 33–44% of the larger dwellings (n = 95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors, with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens.Conclusions and clinical relevanceFood allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spent in the bedroom, mattress dust may be an important source of exposure to food allergens.

A crucial period for the development of the immune system occurs in utero. This results in a high fetal vulnerability to immunotoxic exposure, and indeed, immunotoxic effects have been reported, demonstrating negative effects on immune-related health outcomes and immune functionality. Within the NewGeneris cohort BraMat, a subcohort of the Norwegian Mother and Child Cohort Study (MoBa), immunotoxicity was demonstrated for polychlorinated biphenyls and dioxins, showing associations between estimated maternal intake levels and reduced measles vaccination responses in the offspring at the age of 3. The present study aimed to investigate this link at the transcriptomic level within the same BraMat cohort. To this end, whole-genome gene expression in cord blood was investigated and found to be associated with maternal Food Frequency Questionnaires-derived exposure estimates and with vaccination responses in children at 3 years of age. Because the literature reports gender specificity in the innate, humoral, and cell-mediated responses to viral vaccines, separate analysis for males and females was conducted. Separate gene sets for male and female neonates were identified, comprising genes significantly correlating with both 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and polychlorinated biphenyls (PCB) exposure and with measles vaccination response. Noteworthy, genes correlating negatively with exposure in general show positive correlations with antibody levels and vice versa. For both sexes, these included immune-related genes, suggesting immunosuppressive effects of maternal exposure to TCDD and PCB at the transcriptomic level in neonates in relation to measles vaccination response 3 years later.

Several legumes may induce allergy, and there is extensive serological cross-reactivity among legumes. This cross-reactivity has traditionally been regarded to have limited clinical relevance. However, the introduction of novel legumes to Western countries may have changed this pattern, and in some studies cross-allergy to lupin has been reported in more than 60% of peanut-allergic patients. We wanted to explore cross-reactions among legumes using two newly established mouse models of food allergy. Mice were immunized perorally with fenugreek or lupin with cholera toxin as adjuvant. The mice were challenged with high doses of fenugreek, lupin, peanut or soy, and signs of anaphylactic reactions were observed. Cross-allergic mechanisms were investigated using serum mouse mast cell protease-1 (MMCP-1), antibody responses, immunoblotting and ex vivo production of cytokines by spleen cells. Signs of cross-allergy were observed for all the tested legumes in both models. The cross-allergic symptoms were milder and affected fewer mice than the primary allergic responses. The cross-allergy was reflected to a certain extent in the antibody and T-cell responses, but not in serum MMCP-1 levels. Cross-allergy to peanut, soy, fenugreek and lupin was observed in lupin-sensitized and fenugreek-sensitized mice. Differences in serological responses between primary allergy and cross-allergy might be due to mediation through different immune mechanisms or reflect different epitope affinity to IgE. These differences need to be further investigated.

Lycopene extracted from tomatoes is authorised within the EU as food colouring agent (E160d). The lycopene oleoresin from tomatoes to be used as a novel food ingredient contains 5-15 % lycopene and is prepared by a production process identical to that for the production of the additive E160d, although E160d is prepared using an additional concentration step to obtain an oleoresin that contains 60-70 % lycopene.

For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effect markers provide limited mechanistic insight, and do not allow detection of exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure in human peripheral blood cells (PBMC). Whole genome gene expression changes were investigated following 20 h of in vitro exposure to a high and low concentration of eight genotoxic and three non-genotoxic carcinogenic compounds using whole genome microarrays. Per condition, PBMC of five independent donors were exposed, all in the presence of human liver S9. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic gene sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomarkers of carcinogen exposure.

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a scientific opinion on health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment. This opinion addresses the scientific substantiation of health claims related to microorganisms for which the Panel considered in previous opinions that the data provided were not sufficient to characterise the microorganisms in question. The criteria used by the Panel for the characterisation of food constituents that are bacteria and combinations thereof, which are the subject of health claims, are: species identification by DNA- DNA hybridisation or 16S rRNA gene sequence analysis and/or sequence analysis of other relevant genetic markers; strain identification by DNA macrorestriction followed by pulsed-field gel electrophoresis, randomly amplified polymorphic DNA analysis, or other internationally accepted genetic typing molecular methods. Only when these two criteria are fulfilled is the bacterium considered to be sufficiently characterised. In the case of combinations of several bacteria, the Panel considers that if one microorganism used in the combination is not sufficiently characterised, the combination proposed is not sufficiently characterised. The Panel considers that the food constituents which are the subject of this opinion are not sufficiently characterised. On the basis of the data presented, the Panel concludes that a cause and effect relationship cannot be established between the consumption of the food constituents which are the subject of this opinion and the claimed effects. (C) European Food Safety Authority, 2012.

BACKGROUND:Exposure to the synthetic antimicrobial chemical, triclosan, used in personal care products, has been hypothesized to lead to allergic disease. We investigated whether triclosan exposure was associated with allergic sensitization and symptoms in 10-year-old Norwegian children. METHODS:Urinary concentrations of triclosan were measured in one first morning void from 623 children, collected during 2001-2004. Logistic regression models, controlling for urine specific gravity, parental allergic disease, maternal education, and household income, were fitted for allergic sensitization (either skin prick test positivity or serum-specific IgE ≥ 0.35 kU/l to at least one of 15 evaluated inhalant and food allergens), current rhinitis, and current asthma (questionnaire and exercise challenge test). RESULTS:The adjusted odds ratio (aOR) for allergic sensitization among those in the fourth quartile of triclosan concentration was 2.0 [95% confidence interval (CI): 1.1, 3.4] compared with the reference group (<the limit of detection), and the aOR per log(10) unit increase in triclosan was 1.2 (95% CI: 1.0, 1.4). The aOR for current rhinitis was 1.9 (95% CI: 1.1, 3.4) for the fourth quartile and 1.2 (95% CI: 0.97, 1.4) per log(10) unit increase in triclosan. CONCLUSION:Triclosan concentrations were associated with allergic sensitization, especially inhalant and seasonal allergens, rather than food allergens. Current rhinitis was associated with the highest levels of triclosan, whereas no association was seen for current asthma. These results are consistent with recent findings in other studies and provide additional evidence for an association between triclosan and allergy.

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health claims in relation to rye fibre and changes in bowel function, reduction of post-prandial glycaemic responses and maintenance of normal blood LDL-cholesterol concentrations. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders.The food constituent that is the subject of the health claims is rye fibre. The Panel considers that rye fibre is sufficiently characterised in relation to the claimed effects.Changes in bowel functionThe claimed effect is "gut health". The target population is assumed to be the general population. In the context of the clarifications provided by Member States, the Panel assumes that the claimed effect refers to changes in bowel function. The Panel considers that changes in bowel function such as reduced transit time, more frequent bowel movements, increased faecal bulk, or softer stools may be a beneficial physiological effect, provided these changes do not result in diarrhoea.In weighing the evidence, the Panel took into account that the results of all four human intervention studies considered showed an effect of rye fibre on various outcome measures related to bowel function. The Panel also notes the known mechanism by which rye fibre exerts the claimed effect.On the basis of the data presented, the Panel concludes that a cause and effect relationship has been established between the consumption of rye fibre and changes in bowel function.The Panel considers that in order to bear the claim a food should be at least "high in fibre" as per Annex to Regulation (EC) No 1924/2006. The target population is the general population.Reduction of post-prandial glycaemic responsesThe claimed effect is "carbohydrate metabolism and insulin sensitivity". The target population is assumed to be individuals who wish to reduce their post-prandial glycaemic responses. In the context of the proposed wordings, the Panel assumes that the claimed effect relates to the reduction of postprandial glycaemic responses. The Panel considers that reduction of post-prandial glycaemic responses (as long as post-prandial insulinaemic responses are not disproportionally increased) may be a beneficial physiological effect.In weighing the evidence, the Panel took into account that the three human intervention studies provided from which conclusions could be drawn for the scientific substantiation of the claim, did not show an effect of rye fibre on post-prandial glycaemic responses.On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of rye fibre and reduction of post-prandial glycaemic responses.Maintenance of normal blood LDL-cholesterol concentrationsThe claimed effect is "cardiovascular system". The target population is assumed to be the general population. In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effect refers to the maintenance of normal blood LDL-cholesterol concentrations. The Panel considers that maintenance of normal blood LDL-cholesterol concentrations is a beneficial physiological effect.In weighing the evidence, the Panel took into account that the only human intervention study provided from which conclusions could be drawn for the scientific substantiation of the claim did not show an effect of rye fibre on blood LDL-cholesterol concentrations.On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of rye fibre and maintenance of normal blood LDL-cholesterol concentrations.

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health claims in relation to docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) and contribution to normal cognitive function and maintenance of normal bone. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders.The food constituents that are the subjects of the health claims are "omega-3 and omega-6 fatty acids (GLA)", " gamma-linolenic acid + eicosapentaenoic acid (GLA+EPA)", and " evening primrose oil and fish oil". From the references provided, the Panel assumes that the food constituents that are the subject of the claims are the n-6 fatty acid gamma-linolenic acid (GLA) in evening primrose oil and the n-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in fish oil. The Panel considers that the food constituents, DHA, EPA and GLA, are sufficiently characterised.Contribution to normal cognitive functionThe claimed effect is " brain function (adult & children)". The Panel assumes that the target population is the general population. In the context of the clarifications provided by Member States, the Panel assumes that the claimed effect refers to the contribution to normal cognitive function. The Panel considers that contribution to normal cognitive function is a beneficial physiological effect.No human studies have been provided on the effect of the consumption of a combination of DHA, EPA and GLA on cognitive endpoints.On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of DHA, EPA and GLA and contribution to normal cognitive function.Maintenance of normal boneThe claimed effect is "bone health". The Panel assumes that the target population is the general population. In the context of the proposed wordings, the Panel assumes that the claimed effect refers to the maintenance of normal bone through the promotion of calcium absorption. The Panel considers that maintenance of normal bone is a beneficial physiological effect.In weighing the evidence, the Panel took into account that two of the human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim did not show an effect of the food constituents on bone mineral density, that in a third study acute changes in markers of bone turnover did not predict the occurrence of an effect on bone mineral density and/or mass, and that evidence provided in animal and in vitro studies is not sufficient to predict the occurrence of an effect of the consumption of DHA, EPA and GLA on the maintenance of bone in vivo in humans.On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of DHA, EPA and GLA and maintenance of normal bone.

Fenugreek is a legume mostly used as a spice in Indian-style cooking. Although it has been used since ancient times, its allergenicity has only been reported in the last two decades. It poses special problems as an emerging and often hidden allergen. Fenugreek exposure may have serious implications also for individuals with peanut allergy because of cross-reactivity. Because a new food requires a model specially designed for that particular food, the aim of our study was to develop a food allergy model of fenugreek in mice with anaphylaxis as the endpoint. Mice were immunized perorally using cholera toxin as adjuvant. A two-compartment response surface design with immunoglobulin (Ig) E as the main variable was used to estimate the optimal sensitizing dose of fenugreek, which was further used to evaluate the model. The mice were challenged perorally with a high dose of fenugreek, and signs of anaphylactic reactions were observed. Challenged mice showed high levels of mouse mast cell protease-1, developed specific IgE against several proteins in the fenugreek extract, had elevated levels of IgG1 and IgG2a and showed a general shift towards a Th2 response as determined by ex vivo production of cytokines. Total IgE levels were substantially decreased after challenge. In conclusion, we have established a mouse model of IgE-mediated fenugreek allergy demonstrating anaphylactic reactions upon challenge. There is little information on fenugreek cross-allergy to other legumes like peanut, soy and lupin, and we expect that this model will be a valuable tool in further research on legume allergy.