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Background: Sesame is a relevant food allergen in France. Compared to other allergens there is a lack of food challenge data and more data could help sesame allergy risk management. The aim of this study is to collect more sesame challenge data and investigate the most efficient food challenge method for future studies., Method: Records of patients at University Hospital in Nancy (France) with objective symptoms to sesame challenges were collected and combined with previously published data. An estimation of the sesame allergy population threshold was calculated based on individual NOAELs and LOAELs. Clinical dosing schemes at Nancy were investigated to see if the optimal protocol for sesame is currently used., Results: Fourteen patients (10 M/4 F, 22 ± 14.85 years old) with objective symptoms were added to previously published data making a total of 35 sesame allergic patients. The most sensitive patient reacted to the first dose at challenge of 1.02 mg sesame protein. The ED05 ranges between 1.2 and 4.0 mg of sesame protein (Log-Normal, Log-Logistic, and Weibull models) and the ED10 between 4.2 and 6.2 mg. The optimal food challenge dosing scheme for sesame follows semi-log dose increases from 0.3 to 3000 mg protein., Conclusion: This article provides a valuable update to the existing clinical literature regarding sesame NOAELs and LOAELs. Establishment of a population threshold for sesame could help in increasing the credibility of precautionary labelling and decrease the costs associated with unexpected allergic reactions. Also, the use of an optimal dosing scheme would decrease time spent on diagnostic and thereafter on the economic burden of sesame allergy diagnosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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. This study investigates the risk of an allergic reaction within the milk-, wheat-, hazelnut- and peanut-allergic populations when ingesting UK foods across multiple product categories with and without precautionary allergen labelling., Methods: Allergen risk assessment using probabilistic techniques enables the estimation of the residual risk after the consumption of a product that unintentionally contains an allergen., Results: Within this selection of UK products, the majority that tested positive for an allergen contained a concentration of allergen predicted to cause a reaction in >1% of the allergic population. The concentrations of allergens measured were greater than the VITAL(®) 2.0 action levels and would trigger precautionary allergen labelling. This was found for products both with and without precautionary allergen labelling., Conclusions: The results highlight the need for the food industry and regulators to adopt a transparent, risk-based approach for the communication of the risk associated with potential cross-contact that could occur in the processing facility or production chain., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop., (© 2012 John Wiley & Sons A/S.)

The major allergen parvalbumin was purified from cod muscle tissues, and polyclonal antibodies were raised towards it. The antibodies were tested for specificity and an enzyme-linked immunosorbent assay (ELISA) was developed using these antibodies. The ELISA was applied to measure parvalbumin in cod skin, the starting material for fish gelatin made from deep sea, wild fish. The ELISA was sufficiently sensitive (LLOQ = 0.8 ng ml(-1) in extracts, corresponding to 0.02 µg of parvalbumin per g of tissue), and did not cross-react with common food constituents. Fish gelatin, wine and beer, matrices for the potential use of this ELISA, did not cause disturbance of the assay performance. The data show that the parvalbumin content in cod muscle tissue is 6.25 mg g(-1), while the skins contained considerably less, 0.4 mg g(-1). Washing of the skins, a common industrial procedure during the manufacturing of fish gelatin, reduced the level of parvalbumin about 1000-fold to 0.5 µg g(-1), or 0.5 ppm. From 95 commercial lots of fish gelatin it is shown that 73 are below 0.02 µg g(-1) parvalbumin. From the other 22 lots, the one with the highest concentration contained 0.15 µg g(-1) of parvalbumin. These levels are generally assumed to be safe for fish-allergic individuals.

Lupine has been increasingly used in food applications due to its high nutritional value and excellent functional properties. However, lupine provokes allergic reactions in susceptible individuals. The presence of undeclared lupine residues in foods can pose a serious health risk to lupine-allergic individuals. Therefore, the objective of this research was to develop a sandwich-type ELISA for the detection of lupine residues in foods. Lupine flour derived from Lupinus albus was used to immunize 3 rabbits and a sheep. Pooled lupine-specific antibodies were partially purified from the sera by ammonium sulfate precipitation. A sandwich lupine ELISA with a limit of quantification (LOQ) of 1 ppm was developed by utilizing the rabbit antisera as the capture reagent and the sheep antiserum as the detector reagent. The binding of the antigen-antibody complex was visualized by the addition of commercial rabbit antisheep IgG antibody labeled with alkaline phosphatase with subsequent addition of p-nitrophenyl phosphate substrate to produce a colored product for quantification. Minor cross-reactivity was observed with soy (Glycine max) and black bean (Castanospermum australe). The performance of the lupine ELISA was evaluated in reference food standards (beef frankfurter and apple cinnamon muffin) and laboratory-prepared cooked frankfurters and corn muffins. The mean percent recovery for lupine spiked-frankfurters and corn muffins were 108.4%+/- 8.8% and 103.1%+/- 11.5%, respectively. The sandwich-type lupine ELISA developed in this study provides food manufacturers and regulatory agencies with an effective analytical tool to detect and quantify lupine residues in processed foods.

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.

Thresholds constitute a critical piece of information in assessing the risk from allergenic foods at both the individual and population levels. Knowledge of the minimum dose that can elicit a reaction is of great interest to all food allergy stakeholders. For allergic individuals and health professionals, individual threshold data can inform allergy management. Population thresholds can help both the food industry and regulatory authorities assess the public health risk and design appropriate food safety objectives to guide risk management. Considerable experience has been gained with the double-blind placebo-controlled food challenge (DBPCFC), but only recently has the technique been adapted to provide data on thresholds. Available data thus vary greatly in quality, with relatively few studies providing the best quality individual data, using the low-dose DBPCFC. Such high quality individual data also form the foundation for population thresholds, but these also require, in addition to an adequate sample size, a good characterization of the tested population in relation to the whole allergic population. Determination of thresholds at both an individual level and at a population level is influenced by many factors. This review describes a low-dose challenge protocol developed as part of the European Community-funded Integrated Project Europrevall, and strongly recommends its wider use so that data are generated that can readily increase the power of existing studies.

A structured approach to assess the risk to allergic individuals from food allergens requires as a first step the experimental measurement of minimum eliciting doses in a population that is as representative as possible of the relevant allergic population, using a standardised protocol. These doses are established in controlled challenge studies, but logistical and statistical constraints mean that a proportion of the allergic population may still be at risk of reacting at doses below those which have been or could feasibly be tested. However, statistical modelling of the dose distribution resulting from such challenges permits inferences to be drawn about the proportion of allergic individuals that are likely to react to specified (low) amounts of residual allergen in food. However, different statistical models, which all provide good fits to the experimental data yield different values outside the experimental range. Consequently, the outputs from these models require a form of validation, which demonstrates how close the predictions are to reality. In addition to characterisation of the hazard, for each allergenic food this validation requires information about exposure to undeclared allergen, the actual number of reactions taking place in the wider allergic population, and the prevalence of allergy to that food.

As the current treatment for food allergy involves dietary exclusion of the problem food, information for food-allergic consumers provided on food labels about the nature of allergenic ingredients is important to the management of their condition. The members of an EU-funded networking project, InformAll, focusing on developing strategies for the provision of credible, reliable sources of information for food allergy sufferers, regulators and the food industry, have been considering these matters with respect to food labelling. This paper presents an overview of the genesis of the new EU directive on food labelling, its relevance to food-allergic consumers and the problems that might arise if precautionary labelling becomes more widespread in response to concerns regarding inadvertent allergen contamination in foods. International efforts to define threshold levels of allergens able to trigger a reaction coupled with validated allergen detection methods are essential if the food industry is to implement effective hazard control procedures and address the problems of cross-contact allergens without devaluing the information provided to consumers on food labels.

Background: While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult., Objective: A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods., Methods: In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials., Results: A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 microg of the allergenic food and would continue with doses of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose., Conclusion: A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.

Chicken eggs are used extensively as an excellent source of dietary proteins. These proteins have many functional properties, making them valuable food ingredients. However, eggs are a frequent cause of food hypersensitivity, especially in children. Of major concern to food processors is the inadvertent cross-contact of food products with allergenic residues, which could result in potentially life-threatening reactions in those with a food allergy. The aim of the present study was to develop an enzyme-linked immunosorbent assay (ELISA) for the detection of undeclared egg residues in foods. Commercially purified ovalbumin (OVA) and dehydrated egg white solids were used as antigens to induce antibodies in rabbits and goats. Reference pasta standards and various food samples were extracted, then clarified by centrifugation. Goat anti-egg white antibodies were used as the capture reagent, nonspecific sites were blocked with gelatin, then standard and sample extracts were added. Rabbit anti-OVA antibodies were used as detector antibodies, followed by addition of commercial goat anti-rabbit IgG antibody labeled with alkaline phosphatase and subsequent substrate addition. Twenty brands of egg-free pasta (two lots each) were analyzed using the ELISA. Fourteen common pasta ingredients were also evaluated for cross-reactivity problems in the method. The detection limit of the assay was 1 ppm spray-dried whole egg. Fifty-five percent (22 samples) of the egg-free pasta samples tested positive for the presence of undeclared egg residues, with values ranging from 1 to >100,000 ppm. Minimal cross-reactivity was encountered in general, but portobello mushrooms and basil caused some minor matrix effects. This sandwich-type ELISA method can be used to detect undeclared egg residues in processed foods and to evaluate industrial clean-up operations.

Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources. Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.

A critical evaluation of the available information demonstrates that reactions to natural color additives are rare. Studies of turmeric and carotenoid pigments administered in mixtures with other food colorings failed to definitely identify reactions to either color additive. For carotenoids, the one case report of an adverse reaction was not conclusive. An anaphylactic reaction to saffron does suggest an IgE-mediated reaction, but the high use of saffron as compared with this single report of an adverse reaction suggests that sensitivity to saffron is extremely rare. Numerous reports of reactions to grapes or grape products have been reported in the literature, but no reports of sensitivities to grape skin extract or grape color extract were found. In rare cases, annatto dye may provoke a severe, adverse reaction in individuals with an uncommon hypersensitivity, and may aggravate the symptoms of patients suffering from recurrent urticaria. In its long history of use, there has been only one reported case of anaphylaxis resulting from the ingestion of annatto. Studies designed to investigate the role of annatto in recurrent urticaria sufferers were limited due to the absence of double-blind challenge and placebo controls. A number of cases of adverse reactions to carmine following ingestion have been reported in the literature. These adverse reactions suggest an IgE-mediated hypersensitivity. In many of the reported cases, the cause of sensitization to carmine was topical exposure from the use of carmine-containing cosmetics or occupational exposure to carmine and not from ingestion of carmine-containing foods and beverages. Following sensitization, affected individuals would be sensitive to carmine and the amounts present in foods and beverages could elicit allergic reactions. It is not known whether all individuals with carmine sensitivity induced through topical use are sensitive to the ingestion of carmine in foods. However, reactions to carmine solely because of ingestion are likely to be exceedingly rare due to the low use levels of carmine in foods and beverages. Despite their widespread use in food products, few reports of allergic reactions following ingestion have been reported for the majority of natural color additives. It is concluded that the ingestion of natural color additives presents a very low risk of provoking adverse reactions.

An enzyme-linked immunosorbent assay was developed to detect almonds as potential allergenic contaminants in food. Polyclonal antibodies directed against roasted almonds were partially purified from immunized sheep and rabbits and used as capture and secondary antibodies, respectively, in a sandwich-type, 96-well plate format. Food samples and almond-spiked samples were extracted 1:10 in phosphate-buffered saline at 60 degrees C for 2 h, centrifuged, and applied to wells coated with sheep anti-almond antibody. After incubation, washing, and the addition of rabbit anti-almond antibody, the amount of almond present was detected with the subsequent addition of goat anti-rabbit immunoglobulin G-alkaline phosphatase conjugate and p-nitrophenyl phosphate substrate. Plate absorbances were read at 410 nm, and standard curves were developed in all matrices to quantify unknowns. Antibodies developed were specific for almond; however, some cross-reactivity was observed with extracts of some tree nuts and sesame seeds. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western immunoblotting indicated that sheep anti-almond antibody recognized proteins extracted from black walnuts, Brazil nuts, cashews, hazelnuts, macadamia nuts, pistachios, and sesame seeds in addition to those from almond. The assay was optimized to detect less than 1 ppm of almond and was used successfully to determine almond residues in cereal and chocolate without cross-reacting interferences. A retail survey of 20 brands of cereal demonstrated that the assay produced statistically consistent results. This assay provides a useful quality control tool for the food industry for the protection of consumers allergic to almonds.

The protein and allergen contents of four commercial soybean skin test extracts were tested by SDS-PAGE and immunoblotting using sera from soy-allergic adults. Polyacrylamide gels stained with Coomassie Blue showed an absence of several major soybean proteins, particularly those at higher molecular weights. The acidic subunits of glycinin and beta-conglycinin, major soybean storage proteins, appear to be absent or present in much reduced amounts. Immunoblots with soy-allergic sera indicate alteration, reduction, or loss of IgE-binding in the commercial extracts as compared to extracts of soy flour. In one soy-allergic patient, skin tests revealed a negative response to three of the commercial soybean extracts and a mild response to one extract. Defatted soy flour obtained from two of the four extract manufacturers was extracted in the laboratory using a standard procedure for the isolation of soybean proteins. In one case, the extract still had an abnormal protein profile on gel electrophoresis while in the other case, the new extraction procedure gave significantly improved extraction of soy protein. Preparation methods appear to be partially responsible for the variable allergen content in commercial soybean skin test extracts.

Immunoblots were used to compare the IgE-binding proteins of various soybean products using sera from 7 soybean-allergic patients. Blotting results indicate at least two distinct individualistic patterns of IgE binding to soy proteins. Serum IgE from individuals allergic to both peanuts and soybeans binds to several proteins with molecular weights ranging from 50,000 to 60,000 daltons, while IgE from individuals allergic to soybeans, but not peanuts, binds strongly to a protein(s) with a molecular weight of 20,000 daltons. The soy products tested displayed varying amounts of IgE binding with sera from sensitive patients.

Selective avoidance diets are the most common means of treatment for food allergies and other types of food sensitivities. With IgE-mediated food allergies, adverse reactions can occur in some patients to very small amounts of the offending food; therefore, strict avoidance of the offending food must be accomplished. With other, non-immunological types of food sensitivities, such as lactose intolerance and sulfite sensitivity, the patients are able to tolerate some, although variable, amounts of the offending substance. Thus, the degree of tolerance is an important concern in the construction of safe and effective avoidance diets. Another issue in the development of selective avoidance diets is the presence of the allergen in specific foods. For example, the peanut allergen is a protein which is not present in peanut oil. Consequently, peanut oil is safe to consume for peanut-allergic patients. Cross-reactivity is yet another concern in the development of selective avoidance diets. Cross reactions can occur between related species of legumes, crustacea, eggs, and milk for example. The construction of a safe and effective avoidance diet for food allergies and sensitivities requires consideration of several important issues and is a responsibility that should not be taken lightly.

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction.

Few of the food allergens have been purified and characterized. Complex mixtures of allergens seem to exist in some commonly allergenic foods. Much further research will be necessary to develop any detailed understanding of the chemistry of food allergens.

We have previously demonstrated that peanut oil is not allergenic to peanut-sensitive individuals. Seven soybean-sensitive patients were enrolled in a double-blind crossover study to determine whether ingestion of soybean oil can induce adverse reactions in such patients. All subjects had histories of systemic allergic reactions (urticaria, angioedema, wheezing, dyspnea, and/or vomiting) after soybean ingestion and had positive puncture skin tests with a 1:20 w/v glycerinated-saline whole soybean extract. Sera from six of the seven subjects were tested by RAST assay for the presence of specific IgE antibodies to soybean allergens. All patients had elevated levels of serum IgE antibodies to the crude soybean extract; binding values ranged from 2.3 to 28.1 times that of a negative control serum. Before the oral challenges, all patients demonstrated negative puncture skin tests to three commercially available soybean oils and to olive oil (control). On four separate days, patients were challenged with the individual soybean oils and olive oil in random sequence. At 30-minute intervals, under constant observation, patients ingested 2, 5, and 8 ml of one of the soybean oils or olive oil contained in 1 ml capsules. No untoward reactions were observed with either the commercially available soybean oils or olive oil. Soybean oil ingestion does not appear to pose a risk to soybean-sensitive individuals.

Peanuts are one of the most allergenic foods. The allergic reactions may vary in severity from mild urticaria to severe anaphylactic episodes and death. The prevalence of peanut sensitivity is unknown, but it may affect as many as 10% of allergic individuals. The chemistry of peanut proteins has been extensively studied. Two major protein fractions have been prepared from saline extracts of peanut flour, arachin and conarachin. A major peanut allergen termed "Peanut-1" has been isolated. However, a number of protein constituents, including the arachin and conarachin fractions, have been shown to be allergenic. The ability to diagnose peanut sensitivity accurately has been hampered by the lack of standardized peanut extracts. However, efforts are under way to prepare such standardized reagents. Treatment consists of avoiding peanut protein products and using self-administered epinephrine. A number of peanut protein-containing products are allergenic, although peanut oil is not. The peanut-allergic consumer should be instructed to carefully read labels of foods. This can at times, however, be misleading, because certain foods may be inadvertently contaminated by peanut proteins.

Histamine poisoning results from the consumption of foods, typically certain types of fish and cheeses, that contain unusually high levels of histamine. Spoiled fish of the families, Scombridae and Scomberesocidae (e.g. tuna, mackerel, bonito), are commonly implicated in incidents of histamine poisoning, which leads to the common usage of the term, "scombroid fish poisoning", to describe this illness. However, certain non-scombroid fish, most notably mahi-mahi, bluefish, and sardines, when spoiled are also commonly implicated in histamine poisoning. Also, on rare occasions, cheeses especially Swiss cheese, can be implicated in histamine poisoning. The symptoms of histamine poisoning generally resemble the symptoms encountered with IgE-mediated food allergies. The symptoms include nausea, vomiting, diarrhea, an oral burning sensation or peppery taste, hives, itching, red rash, and hypotension. The onset of the symptoms usually occurs within a few minutes after ingestion of the implicated food, and the duration of symptoms ranges from a few hours to 24 h. Antihistamines can be used effectively to treat this intoxication. Histamine is formed in foods by certain bacteria that are able to decarboxylate the amino acid, histidine. However, foods containing unusually high levels of histamine may not appear to be outwardly spoiled. Foods with histamine concentrations exceeding 50 mg per 100 g of food are generally considered to be hazardous. Histamine formation in fish can be prevented by proper handling and refrigerated storage while the control of histamine formation in cheese seems dependent on insuring that histamine-producing bacteria are not present in significant numbers in the raw milk.