Proc. Nutr. SOC. (1983), 42,233 23 3 Adverse reactions to food additives By BARBARA MACGIBBON, Department o f Health and Social Security, Hannibal House, Elephant and Castle, London SEI 6TE The first published report of an adverse reaction to a food additive was that provided by Lockey (1959). He described urticaria in a patient who was given steroid therapy, the formulation of which contained tartrazine. In 1973 the Ministry of Agriculture, Fisheries and Foods Food Additives and Contaminants Committee produced an interim report on the Review of the Colouring Matter in Food Regulations. In the report the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment noted that there had been a number of reports of hypersensitivity reactions following the experimental ingestion of certain food colours; the evidence suggested that such reactions were rare. The Committee further noted that there was suggestive evidence of idiosyncratic reactions following ingestion of food containing usual levels of colouring. They were concerned about the situation but as hypersensitivity to food constitutes a general problem and is not confined to colours, they felt that useful recommendations could not be made until clearer evidence from well-controlled studies in man became available. In 1979 the Commission of the European Communitys Scientific Committee for Food reported on certain colouring matters and noted similar problems. It is obviously easier to detect the presence of colouring matter than other additives in foods and there can be no doubt that this situation has led to colours being tested more frequently than other additives for their potential to produce adverse reactions in sensitive individuals. Furthermore, the reasons for using colouring matters (for example, in food to replace colour lost in processing, to inhibit or mask fading, and to ensure uniformity in the appearance of a particular product; and in medicines to aid correct identification) are not universally accepted. The Scientific Committee for Food, knowing of concern about the use of colouring matters in food, were also aware of the possibility that other food additives could provoke adverse reactions. The Committee therefore suggested to the Commission, in 1979, that a working group should be set up to consider adverse reactions to ingested additives present in food, drug formulations and cosmetics. This working group presented its findings to the Scientific Committee for Food in 1981 and its report was published the following year (Commission of the European Community, 1982). Much of the following presentation will be based on participation in this working group, but an attempt will be made to emphasize those questions of particular concern, from a regulatory point of view, for the UK. 234 SYMPOSIUM PROCEEDINGS I983 What is the extent of the problem? The main tasks identified by the working group were to review the available evidence in order to define the size of the problem and to establish a scientific basis for recommending what should be done in terms of research as well as regulatory action. It was not only necessary to reach some conclusion about the frequency of adverse reactions attributable to ingestion of additives, but to gain some idea of the extent of the problem also in terms of whether few or many additives were involved and the range of clinical manifestations and their severity. One of the difficulties in arriving at an estimate of the frequency of adverse reactions is that of finding reliable evidence associating an adverse reaction with the ingestion of an additive. Such adverse reactions are clinically indistinguishable from allergic responses to a variety of foods. Even in the latter case there may be difficulty in relating symptoms to food ingestion, particularly if the onset of symptoms is delayed or they are non-specific in type. It is even more difficult to identify a particular additive in such a causal relationship, especially since most of the reactions have not as yet been shown to be immunologically determined and there is, therefore, a lack of specific or useful diagnostic tests such as the skin test, or radio-allergosorbent test for specific IgE antibodies. The existing means of determining the relationship between an additive and an adverse reaction are time consuming and include history taking and observations on avoidance diets and after challenge testing. Unequivocal evidence of such an effect requires double- blind challenge testing with placebo on more than one occasion. Results from such studies are not readily available and most of the data considered are less satisfactory. In considering the types of clinical manifestation which may result from adverse reactions to food additives, it is clear that it is easier to obtain evidence in patients whose respiratory or skin problems are aggravated by ingestion of particular additives, than to suspect that rather non-specific gastrointestinal sy