Key issues for the assessment of the allergenic potential of genetically modified foods: breakout group reports - Genetically Modified Foods Mini-Monograph

Environmental Health Perspectives, June 15, 2003 by Dori R. Germolec, Ian Kimber, Lynn Goldman, Mary Jane Selgrade

On the final afternoon of the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods," held 10-12 December 2001 in Chapel Hill, North Carolina, USA, speakers and participants met in breakout groups to discuss specific questions in the areas of use of human clinical data, animal models to assess food allergy, biomarkers of exposure and effect, sensitive populations, dose-response assessment, and postmarket surveillance. Each group addressed general questions regarding allergenicity of genetically modified foods and specific questions for each subject area. This article is a brief summary of the discussions of each of the six breakout groups regarding our current state of knowledge and what information is needed to advance the field. Key words: animal models, food allergy, hazard identification, IgE, immunoassay, postmarket surveillance, safety assessment, sensitization, skin prick test, threshold. Environ Health Perspect 111:1131-1139 (2003). doi:10.1289/ehp.5814 available via http://dx.doi.org/[Online 19 December 2002]

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On the final afternoon of the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods," held 10-12 December 2001, in Chapel Hill, North Carolina, speakers and participants met in breakout groups of 8-12 individuals to discuss key issues in the following areas: use of human clinical data, animal models to assess food allergy, biomarkers of exposure and effect, sensitive populations, dose-response assessment, and postmarket surveillance. Each group was asked to address general questions regarding what can be done to assess the potential allergenicity of genetically modified (GM) foods and what is needed to improve this process, as well as questions specific to each particular topic. In many instances, the discussion topics overlapped such that a number of topics were addressed by multiple groups, and in some cases their conclusions differed. Following is a brief summary of the discussions of each of the six breakout groups regarding our current state of knowledge and what information is needed to advance the field. Each breakout group contained individuals with a wide variety of expertise so that the subject material could be covered fully. The text below is an effort to capture the expertise and opinions of diverse participants and as detailed in the text below, in some instances consensus was not achieved.

Use of Human Clinical Data

How important are the following end points in hazard identification and dose response: immune indicators of sensitization (IgE, skin test positivity), clinical symptoms from skin, gut, respiratory tract after provocation (DBPCFC), and anaphylaxis? A clinical syndrome suggestive of an IgE-mediated reaction (flushing, urticaria, angioedema, wheeze, stridor, abdominal pain, vomiting, or cardiovascular collapse) after the ingestion of an allergenic food can be confirmed with a skin prick test (SPT) or serum-specific IgE. However, in the absence of a clinical history suggestive of allergy, IgE detection, whether SPT or specific IgE, serves as a good indicator of sensitization but not necessarily of disease. Conversely, in the clinical setting, the absence of detectable IgE may be useful at excluding IgE-mediated food allergy. However, this depends somewhat on the specific antigen and techniques used. It is possible to obtain positive SPT results in individuals who test negative for serum IgE, as antigen-specific IgE may be predominantly cell bound when present at low levels. Interpretation of the usefulness of SPT or food-specific IgE rests with the comparison of SPT/specific IgE results with the outcome of double-blind, placebo-controlled food challenge (DBPCFC), which is currently the "gold standard" for determining food allergy. Approximately 50% of positive SPTs correlate with confirmed DBPCFCs, suggesting that sensitization to food allergens occurs in the absence of clinical symptoms (Bock et al. 1977, 1978; Eigenmann and Sampson 1998). The magnitude of the SPT or specific IgE measurement is useful in predicting the likelihood of clinical allergy (as confirmed by DBPCFC) but is not useful in predicting severity (Eigenmann and Sampson 1998; Sampson 2001).

The DBPCFC is an excellent method for confirming suspected allergy. In a controlled setting with experienced clinicians, the DBPCFC can be safely performed (Bock et al. 1978, 1988; Watson 1995; Williams and Bock 1999). The rapidity of IgE-mediated reactions (> 90% within 1 hr) allows the DBPCFC to reproduce objectively IgE-mediated symptoms resulting from the food administered.

Theoretically, any food containing a protein could elicit an allergic reaction; however, eight common foods are responsible for > 90% of food allergies. The remaining 10% of food allergies result from over 150 different proteins (Hefle et al. 1996). Data are becoming available on threshold doses required to provoke an allergic reaction in previously sensitized individuals. Recently, the results of 10 independently conducted clinical challenge studies have been reported (Taylor et al. 2002). In these 10 well-defined clinical studies involving peanut, milk, egg, fish, and mustard allergens, 0.25 mg peanut protein (equivalent to 1 mg whole peanut) was the lowest provoking dose and was therefore considered to be the lowest observable adverse effect level (LOAEL) for elicitation. Of the 10 studies, one reported four subjects, from a study cohort of 74, who developed an allergic response to this LOAEL. In the other nine studies, no other individuals with this degree of sensitivity were identified. It should also be noted, however, that the responses in these four individuals were mild and reversed spontaneously (Taylor et al. 2002).