Environmental Toxicology and Pharmacology 4 (1997) 3 – 7
Food allergy and intolerance: an international chemical safety perspective1 Edward Smith * Programme for the Promotion of Chemical Safety, World Health Organization, 1211 Gene6a 27, Switzerland
Abstract Chemical safety is concerned with the assessment of human health (and environmental) risks and their management. The safety of chemicals in food, present as normal constituents, intentional additives, contaminants or residues is part of chemical safety. Morbidity and mortality due to allergenic chemicals and allergic hypersensitization are being addressed on a global basis. As part of this, international efforts are being made to establish the prevalence of respiratory and dermal allergies in all countries and it is timely to extend this to food allergies. A number of international organizations are involved in the assessment of chemical risk and risk management. Information exchange is a vital part of these processes. The International Programme on Chemical Safety is an example of a cooperative programme of three organizations with close links and coordination with other bodies and organizations concerned with safe and sustainable use of chemicals. © 1997 Elsevier Science Ireland Ltd. Keywords: Chemical safety; Food allergy
1. Introduction: international chemical safety Chemical safety is the prevention and management of the adverse effects, both short-term and long-term, to humans and the environment from the production, storage, transportation, use and disposal of chemicals, natural and synthetic. This includes chemicals in foods and beverages, whether present as natural constituents, intentional additives or contaminants. Most chemicals are intrinsically toxic but can be used safely provided their risks are recognized, assessed and where necessary, precautionary measures are applied. The International Programme on Chemical Safety (IPCS) implements the evaluation of chemical hazards, their human and environmental effects and develop risk assessment methodology. IPCS is concerned with the toxicology of organs and systems. One such area is the immune system and allergies to natural and synthetic
* Tel.: +41 22 7913576; fax: + 41 22 7914848. 1 The views expressed are those of the author and do not necessarily reflect the decision or stated policy of the World Health Organization.
chemicals are being actively considered. Globally, allergies are a significant cause of morbidity and in some instances mortality and food allergies cannot be ignored. The IPCS works closely with national governments and institutions in the pursuit of its objectives through a variety of scientific meetings, such as this symposium. The IPCS has been operating as a cooperative programme of the United Nations Environment Programme (UNEP), the International Labour Organisation (ILO) and the World Health Organization (WHO) since 1980. Chemical safety received a fresh impetus at the 1992 United Nations Conference on Environment and Development held in Rio de Janeiro, Brazil. A major theme was sustainable development, i.e. the recognition that many human activities, including those involving chemicals, while beneficial economically, can have adverse effects on health and the environment and these two aspects need to be reconciled. The conference endorsed the strengthening of national and international coordination in the area of chemical risk assessment and management (UNCED, 1992).
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Other bodies such as the UN Food and Agriculture Organisation (FAO), the UN Industrial Development Organisation (UNIDO) and the Organisation for Economic Co-Operation and Development (OECD) have also been active in the chemical field and in response to the need for strengthened coordination of chemical safety an Inter-Organization Programme for the Sound Management of Chemicals (IOMC) has been established. The IOMC coordinates the efforts of six international organizations — WHO, UNEP, ILO, FAO, UNIDO and OECD — in the assessment and management of chemicals. The IOMC takes note of the chemical safety-related activities taking place in each of the cooperating organizations and their outputs-reports, conclusions and recommendations and helps to disseminate their outputs. This symposium figures on the IOMC list of activities and its outputs will be circulated globally. Another international mechanism established at the same time is the Intergovernmental Forum on Chemical Safety (IFCS) composed of representatives of national governments which have consultative and advisory functions. The IFCS also receives information on chemical safety-related activities. Thus, there are now efficient international mechanisms for the rapid dissemination and use of information on all chemical safety matters. In the international context WHO, FAO and OECD have considered food allergy as part of their food safety activities. Recent meetings include an FAO Technical Consultation on Food Allergies in 1995. This reviewed the problem and recommended that labeling be improved. Thus, ingredients or additives which are the products of allergenic foods should be named on the food label and the 25% level for a composite ingredient be reduced (FAO, 1995). In 1996 a Joint FAO/WHO Consultation on Biotechnology and Food Safety considered as a special issue the allergenicity of foods produced through biotechnology. Resulting recommendations included the need for caution in gene transfer from commonly known allergenic foods, the limitations of labeling and appropriate actions in respect of foods containing new protein(s) that have the characteristics of an allergen (FAO/WHO, 1996).
2. Factors in health impact assessment Typical problems encountered with assessing the human health impact of any chemical on a global basis are; availability of data, their quality and comparability, diagnostic criteria, standards of clinical and epidemiological monitoring, terminology and national perceptions. Terms and definitions are not merely semantic issues. In international communication, even within one language, the potential for misunderstanding exists and it is crucial to agree precise meanings and
definitions of words and terms. This usually has to be on an arbitrary basis. International harmonization of terminology in the field of chemical safety is considered critical for an effective global approach to assessing and managing chemical risks and is being vigorously pursued. In examining and elucidating adverse health effects, small meetings of dedicated scientists, drawn from different countries and regions, meeting under the aegis of international bodies such as the IPCS have proved highly effective in identifying salient issues and making recommendations on their investigation. In the international context such recommendations are taken seriously and the record of implementation is good.
3. Food allergy and intolerance Food allergy (and intolerance) have been known since antiquity. In the past, food allergy and intolerance tended to be regarded as minor health problems and it is only in this century that they have received more serious consideration and research. Concern was stimulated in 1975 by the suggestion that food constituents could have behavioral effects (Feingold, 1975) and more recently by anaphylactic reactions produced by food allergens (Sampson et al., 1992; BruijnzeelKoomen et al., 1995). Also, the realization that food allergy during infancy can initiate a chain of development of other allergies, placed further emphasis on the importance of diagnosis and management. Food allergy and its induction, like other allergies, may be influenced by exposure to natural and synthetic chemicals in the environment. If exposure results in modulation of the immune system there may be increased susceptibility to allergic hypersensitization, greater allergic reactions in hypersensitized individuals, hypersensitisation to more allergens and interference with the development of tolerance. Like many other adverse health effects both environmental and genetic factors are involved. Environmental and lifestyle factors can interact with the developing immune system and the foundations of allergy can be laid in early life, even in utero. Atopicity is an important factor. The risk of a child developing atopicity is increased proportionately if one or both parents are atopic (Bjo¨rksten and Kjellmann, 1987). The extent to which these factors interact and the importance of environmental influences on the induction of allergy, food and other types, is crucial to the management of risk, particularly to primary prevention. There have been suggestions that environmental pollution may be involved in increasing the prevalence of respiratory tract allergies (Ring, 1996) or that absence of childhood infections may be much more important (Cookson and Moffatt, 1997). Immunotoxic chemicals
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can disturb the balance of the immune system and modify responses to allergens (Van Loveren et al., 1996). High concentrations of pollutants such as suspended particles, automobile exhaust, ozone, sulfur dioxide and oxides of nitrogen are present in the atmosphere in countries where an increased prevalence of allergies has been reported. However, in the case of asthma, which has been extensively studied, controled prospective trials comparing West and East Germany with their differences in environmental pollution showed that the prevalence of respiratory allergies, including asthma, was higher in the less polluted West while atopic eczema was more prevalent in the East (von Mutius et al., 1994; Ring et al., 1995). Indoor allergens, parental smoking and proximity to roads with high motor traffic density appeared to be among relevant risk factors (Keil et al., 1996). Whether there is an equivalent situation for food allergies is not clear but environmental risk factors would merit examination. While there are data from a number of countries on the prevalence of adverse reactions to foods, particularly allergies, study populations tend to be small. For clinical reasons many studies focus on specific foods and their allergens. Thus, global information on these adverse reactions and the prevalence of food allergies and intolerances is incomplete (Sampson, 1993; FAO, 1995). It has been estimated that the prevalence of adverse reactions to food in children aged less than 3 years is 8%, with food allergies constituting 2–4% (Bock, 1987). Estimates of the prevalence of cow’s milk allergy in infants range between 0.5 and 10% (Dean, 1995). In adults an estimated prevalence is around 1% (Anderson, 1991; Sampson and Metcalfe, 1992). Without reliable prevalence data determining the health impact at population level is difficult and it is speculative to talk about changing patterns and incidence. Contributing factors to lack of sound prevalence data are; insufficient clarity in definitions of terms, imprecise diagnostic criteria and national perceptions influencing the interest of decision makers and clinicians in investigating the problem. The signs and symptoms of adverse reactions to food, tend to be non-specific and differential diagnosis is important. However, many people who have a repeated adverse reaction to a food instinctively exclude it from their diet and may not seek medical advice. Without establishing a sound baseline of prevalence and types of adverse effects it is not justifiable to draw general conclusions. The diagnosis of food allergy and the distinction between allergy and intolerance is not simple (Sampson, 1993). Similar symptomatologies are also found with toxic reactions to food. It is tempting to make a diagnosis on the basis of symptoms and medical history but this will not discriminate between various
types of adverse reactions to food and more importantly, will not separate allergy from intolerance. Comparison of responses to questionnaires and clinical investigation shows that many more people think they have a food allergy than is the case (Jansen et al., 1994). Accurate diagnosis requires not only well developed clinical skills but relatively sophisticated tests and procedures, most being resource demanding (Sampson et al., 1992). The elucidation of the cause of a food allergy can be complicated. Batteries of ‘standard’ food allergens are available for skin testing but these may not be representative in all cases and may require modification to meet national needs. Sensitization by one route can result in allergic responses elsewhere (Burks, 1995). Cross reaction to airborne allergens can manifest as food allergy. Inhalation of food allergens can elicit respiratory effects. Food allergens can elicit dermal reactions (Bruijnzeel-Koomen et al., 1995).
4. Exposure to food allergens Food allergens are generally proteins or glycoproteins in the molecular weight range 10 000–40 000 (Sampson and Metcalfe, 1992; Metcalfe, 1995), but allergic reactions have been reported to proteins with molecular weights as low as 3000 and as high as 90 000 (King et al., 1995). Some allergenic proteins are heat and protease-stable. Potentially allergenic proteins are found in all groups of foods—dairy products, eggs, fish, seafood, meat, cereals, legumes, leaf and root vegetables, fruits, seeds and nuts. The list of individual foods associated with allergic reactions is lengthy (Moneret-Vautrin, 1986). Some food allergens can produce anaphylaxis, which may be fatal (Sampson et al., 1992; Bruijnzeel-Koomen et al., 1995), e.g. peanuts, tree nuts, eggs and milk (Ownby, 1995). With extensive world trade in foodstuffs, including foods formerly regarded as exotic, populations are being exposed to new food allergens and components. A food can contain a number of allergenic proteins causing antibody formation. Cow’s milk contains over 20 allergenic protein components and eggs contain allergenic proteins in the egg-white and yolk. There are some regional and national variations reflecting dietary patterns, for example, fish allergy is common in Scandinavia, rice allergy in Asia and peanut allergy in the USA. Other food constituents and contaminants have been associated with food intolerances. Some food additives—colours, preservatives, flavours—have been implicated in food allergies and intolerances (Simon and Stevenson, 1993).
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Language is the means of communication but it can also confuse. Developed languages are not strictly literal. Even within a single language there are ambiguities and the potential for confusion increases when moving between languages. The terms ‘food sensitivity’ or ‘food hypersensitivity’ are often used to cover all adverse reactions to food. This can lead to a perception that all adverse reactions to food have an allergic basis. There needs to be a much clearer definition with ‘food allergy’ used only for an immunologically-mediated adverse reaction (allergic hypersensitivity) to a food component, preferably with demonstration of IgE-mediation. However, the possibility of non-IgE-mediated reactions cannot be excluded although the evidence for this at present, is unclear. Food intolerance needs to be clearly distinguished from food allergy (Brostoff et al., 1984) For a start it is more common than food allergy and a diagnosis of food intolerance might be more appropriate until an allergic mechanism has been demonstrated. In terms of definition ‘food intolerance’ is non-immunologically-mediated and may be due to various factors comprising toxic contaminants, pharmacological properties of food components, metabolic factors, or idiosyncratic/undefined responses. Moves have been made to put terminology on a consistent footing and the contributions of the European Academy of Allergology and Clinical Immunology (EAACI) (Bruijnzeel-Koomen et al., 1995) and the European Society of Pediatric Allergy and Clinical Immunology (ESPACI) (Businco et al., 1993) serve as examples.
In the management of adverse human health effects the primary goal is prevention. Predictive testing is one method of primary prevention because it enables risks to be identified and controled. A critical stage for primary prevention is during early life when there is the risk of acquiring a food allergy. The infant has an immature gut immune system and is susceptible to hypersensitization to the many food allergens being absorbed. Measures suggested include breast feeding, avoidance of cow’s milk, use of vegetable based infant formulae, hypoallergenic infant formulae and delayed introduction to baby foods (FAO, 1995). Their efficacy is still being evaluated. Labeling is an important part of secondary prevention because it enables individuals to avoid foods to which they are hypersensitized. The extent of food allergens and the response to low concentrations pose problems in labeling because of the number of constituents in a processed or manufactured food that might have to be listed and for food commodities in international trade the linguistic implications are formidable.
6. Predictive testing Predictive testing using in vivo and in vitro experimental models is a cornerstone in identifying chemical hazard and assessing risk. In the case of food allergens, validated experimental models do not appear to be available. Food proteins in the molecular weight range for food allergens may be considered as potential hazards and data bases on structure-activity relationships (SAR) provide useful information. Knowledge of food allergens has been obtained from human diagnostic and other studies and wide dissemination of this information with full characterization of the allergenic proteins is necessary. For foods or food components produced by biotechnology, the safety assessment is particularly important to ensure that hazardous products do not become available (FAO/WHO, 1996).
8. Conclusion The prevalence of food allergy in percentage terms looks small but if the figures were applicable worldwide the numbers suffering from food allergies would be large and the health impact considerable. It is important to determine this. The increasing understanding of the nature and causes of adverse reactions to food, makes a major contribution to diagnosis, treatment, prevention and control. The efficient dissemination and use of the information being produced by clinicians and researchers will make a major contribution to dealing with food allergies on a global basis.
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