Safety of Genetically Engineered Foods Approaches to Assessing Unintended Health Effects (2004) / Chapter Skim
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6 Methods for Predicting and Assessing Unintended Effects on Human Health
6 Methods for Predicting and Assessing Unintended Effects on Human Health
Pages 127-174
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From page 127... ...
Even in cases where food composition changes are known, current understanding of the potential biological activity in humans for most food constituents is very limited. This becomes most evident when considering mixtures or diets consumed by human populations and then attempting to predict adverse health consequences from chronic intake of specific foods.
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From page 128... ...
The general conceptual approach for predicting and detecting adverse health outcomes discussed in this chapter is based on a risk assessment strategy proposed by the National Research Council (NRC, 1983) and relies on "substantial equivalence" to illustrate distinctions that may exist between foods modified by genetic engineering and those modified through traditional (non-GE)
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From page 129... ...
The use of substantial equivalence is one approach used to illustrate distinctions that may exist between foods modified by genetic engineering compared with traditional (non-GE) methods for modifying food composition.
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From page 130... ...
However, this possibility is rather unlikely to occur in cases of GE foods that have substantially altered compositional traits compared with their conventional counterparts. In other cases, GE foods may be judged to be substantially equivalent to their conventional counterparts except for specific differences, including the introduced traits.
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From page 131... ...
Assessment of the safety of the introduced traits or novel proteins can be approached in a similar fashion, no matter what the source of the inserted gene. This approach could also be applied to the identification of compositional differences and the safety assessment of food produced by all means of genetic modification.
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From page 132... ...
. However, the possibility of transferring and incorporating novel genes from GM foods into cells has been investigated in animal models, humans, and microorganisms (gut bacteria)
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From page 133... ...
In summary, the safety of GE products should be predicated on the characteristics of the novel protein or other product expressed by the gene, rather than on the safety of ingesting DNA or the possibility of horizontal transfer of novel genetic material to humans or gastrointestinal microorganisms. Safety Evaluation of Marker Genes and Their Products Products of marker genes are obvious predictable differences that should be highlighted in initial substantial equivalence comparisons.
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From page 134... ...
However, subchronic animal toxicological studies have also been conducted on some of the novel proteins and on GE food. As noted previously, the design and interpretation of animal toxicological studies with whole food, including GE food, is challenging.
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From page 135... ...
However, an assessment of the acute toxicity of the novel proteins introduced into GE food is one approach to preventing unintended health consequences. Nevertheless, evaluation of the acute oral toxicity of a GE food and the novel proteins it may contain should be considered.
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From page 136... ...
Premarket Allergenicity Assessment Virtually all known food allergens are proteins, so the allergenic potential of all novel proteins must be determined. In 1996 a decision-tree approach for assessing the potential allergenicity of GE food was developed that relied upon evaluating the source of the gene, the amino acid sequence homology of the newly
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From page 137... ...
. Several approaches should be considered to improve the assessment of the potential allergenicity of novel proteins.
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From page 138... ...
Food containing such novel proteins would need to be labeled to protect allergic consumers. cA novel protein that either has no sequence similarity to known allergens or has been derived from a less commonly allergenic source with no evidence of binding to immunoglobulin-E (IgE)
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From page 139... ...
A third approach to assessing the allergenicity of novel proteins is targeted serum screening, which involves the determination of the binding of a novel protein of interest to serum IgE antibodies obtained from individuals who are allergic to materials that are broadly related to the source of the novel gene. For example, the source for a novel gene, such as a dicot plant, may not be associated with known allergies, but other dicot plants, including peanuts and various specific tree nuts, are known food allergens.
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From page 140... ...
The loss of biological functions may not completely correlate with the loss of allergenic activity, so the inability to detect a novel protein after heating does not demonstrate that the protein is no longer present in some altered form that may be allergenic. Nutritional Evaluation of Modified Food Products Thus far the genetic engineering of plants and animals has been aimed primarily toward enhancing agricultural productivity or improving agronomic characteristics.
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From page 141... ...
Any potential hazards that are identified through this process that may be associated with unique components introduced into the food by genetic engineering are assessed. When health hazards become apparent to regulatory agencies, the commercialization of GE food is likely to be stopped without any attempt to determine the overall risk using a complete risk assessment approach.
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From page 142... ...
Additionally, as noted earlier, considerable focus is placed upon the unique components, usually proteins, that are produced by the inserted gene. The selection of a suitable comparator is a pivotal and complex decision.
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From page 143... ...
Furthermore, other naturally occurring food components, such as antinutrients, could be present at much higher levels than the substances that result from the genetic engineering process, so observed abnormalities in the animals could be attributable to other factors. In cases in which the GE food is
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From page 144... ...
While the application of animal toxicology tests is of debatable value, in the case of GE food in which the novel protein is expressed at a low level, is susceptible to pepsin hydrolysis, and is not similar to known protein toxins, such testing will assume greater importance in situations in which the GE food is not substantially equivalent to its traditional counterpart and is significantly altered in its composition. In such cases, appropriate animal toxicology testing with whole food should be considered on a case-by-case basis in parallel with toxicological evaluation of individual food constituents (including novel proteins)
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From page 145... ...
The possibility exists that a novel protein contained in GE food could either be or become an allergen. However, levels likely exist below which novel proteins would be unable to elicit allergic sensitization in susceptible individuals.
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From page 146... ...
Neither of these examples was predicted to have adverse health consequences, but they do demonstrate that unintended effects can occur. The likelihood of unintended modifications leading to adverse outcomes is determined, to a large extent, by the method or methods used to produce intended changes.
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From page 147... ...
Identification of Potential Hazards The first step in assessing the potential of an adverse outcome is to identify suspected compositional changes and then assess their potential for adverse health effects. Adverse outcomes may be divided into two major subgroups: adverse consequences of unintended modifications that accompany presumably targeted changes, and unintended consequences of successful, highly targeted, intended modifications.
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From page 148... ...
Although field trials were conducted, there is no evidence to suggest that the Brazil nut gene crossed over into other soybean varieties. Although dietary trans fatty acids were not introduced through genetic manipulation of a food, their increased consumption is among the best examples of unintended health consequences of a fully predictable compositional change in food.
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From page 149... ...
Accordingly, on a dose-response basis, these novel proteins and components would not be expected to provoke unexpected adverse health effects unless they are profoundly toxic or allergenic. This situation could change considerably with the introduction of future GE products that are intentionally modified to be significantly different from their traditional counterparts.
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From page 150... ...
and the GE food is substantially equivalent to its conventional counterparts in all other respects. The impacts of altered levels of endogenous allergens on human health are questionable, even if they were proven to occur.
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From page 151... ...
Nature of Modification The nature of compositional changes also merits consideration, for example, the magnitude of additions or deletions of specific constituents and modifications that may result in enhanced allergenic potential. It is also important to acknowledge that the most serious challenges of anticipating unintended human health consequences will be presented by components for which there is little documented knowledge.
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From page 152... ...
Where inferences warrant interpretation beyond assessments of association, reference must be made to established criteria for causality. When toxicological studies suggest a hypothetical adverse health consequence in relation to a new GE food, postmarket epidemiological studies can be targeted to particular health consequences and, if a suspected adverse outcome is documented, aid in preventing recurrences of similar unintended effects.
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From page 153... ...
. Epidemiological studies using data from several countries suggested dietary trans fatty acids were associated with population rates of CHD death (Kromhout et al., 1995)
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From page 154... ...
. Dose-Response Assessments Predicting the functional significance of unintended modifications of food composition is likely to present special challenges because of the limited information available regarding dose-response relationships for most food constituents, even those of known functional relevance.
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From page 155... ...
This is likely to become increasingly prominent in assessments of nutrient deficiencies, toxicities of nutrients and other food constituents, and other types of adverse outcomes. Exposure Assessment Epidemiological studies are characterized by investigating the associations between exposures and health outcomes in defined population groups.
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From page 156... ...
Individual Level: Traditional Methods of Dietary Intake Assessment The three forms of dietary intake assessment most commonly used in epidemiological studies are 24-hour recalls, food records, and food-frequency questionnaires (Willett, 1998)
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From page 157... ...
. The large measurement error associated with these methods continues to plague epidemiological studies of food and food components.
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From page 158... ...
The data collected from these cards provide useful information to both processors and retailers who can tailor production or stock store shelves to meet specific local demands or to conduct targeted marketing. With consumer consent, these data have the potential for inclusion in epidemiological studies as a measure of exposure to specific food types.
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From page 159... ...
This approach also may be used when exposure to specific GE products is identifiable, but no information is available about specific health effects, whether intended or unintended, that may be associated with its consumption. Linking Exposure to Outcomes Specific Studies If there are hypothetical health risks based on animal studies or premarket volunteer testing that are associated with GE food or food products, epidemiological studies can be designed specifically to evaluate these possible risks.
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From page 160... ...
Prospective and retrospective, population-based, and observational studies generally document significant associations of specific dietary and other related lifestyle patterns with good or poor health outcomes (Rimm et al., 1993; Stampfer et al., 1993)
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From page 161... ...
Inadvertent changes in the content of these active agents in food, in theory, could have long-term risks or benefits. This situation is particularly challenging given historical difficulties in evaluating the health effects of such dietary components as sodium, saturated and trans fatty acids, and antioxidants.
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From page 162... ...
Thus in this context, Bayesian approaches for model-based methods refers to an estimation procedure that makes complex models of health outcomes in relation to multiple exposure measures amenable to evaluation. In summary, new statistical methods are emerging to address the complex pathways of basic physiology and disease etiology (Boguski and McIntosh, 2003)
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From page 163... ...
Such physiologically imposed requirements intersect with specific eating patterns in the United States such that the average 1-year-old child consumes over 20 times per body weight more apple juice and two to seven times more bananas and carrots than do adults. Marked variability in intakes of specific food is likely to increase as niche markets and specialty foods proliferate and ethnic diversity increases.
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From page 164... ...
. In the validation substudy, a more detailed dietary intake assessment would be performed using repeat measures.
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From page 165... ...
. Health Monitoring In specifically designed epidemiological studies or in surveillance studies using routinely collected data, the health outcomes studied fall into four broad classes: mortality (disease specific)
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From page 166... ...
New approaches should be based on a risk-assessment strategy proposed by the National Research Council (NRC, 1983) and rely on "substantial equivalence" to illustrate distinctions that may exist between foods modified by genetic engineering compared with those modified through traditional (non-GE)
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2000. Critical windows of exposure for children's health: Cancer in human epidemiological studies and neoplasms in experimental animal models.
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From page 168... ...
1994. Postmarketing surveillance of food additives.
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From page 169... ...
2000. Trans fatty acids and plasma lipoproteins.
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From page 170... ...
1995. Dietary saturated and trans fatty acids and choles terol and 25-year mortality from coronary heart disease: The Seven Countries Study.
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From page 171... ...
2001. Association be tween trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: A prospective population-based study.
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From page 172... ...
1998. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.
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From page 173... ...
1993. Health aspects of marker genes in genetically modified plants.
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