Part 2 of 2
In Vivo StudiesFurther analysis of allergenicity can be performed using human subjects known to be allergic to the donor protein. This consists of allergy prick skin testing using suitable concentrations of extracts of the host food, the native donor food, and the GM food. These extracts are pricked into the epidermal layers of the allergic individual’s skin, and observed for a localized allergic reaction consisting of a hive at the test site within 15 minutes. This reaction indicates that the test subject’s immune system has identified that particular food as carrying an allergen against which the subject has previously developed IgE antibodies. If desired, these volunteers can be further evaluated by DBPCFC with the GM food to confirm the presence or absence of that particular allergenic protein in the GM food. The confirmation of the presence of an allergen by DBPCFC is the most reliable method, but often is not practical because it requires the physical presence of human volunteers. DBPCFC will most likely be necessary for the final evaluation of a GM food containing a gene from a known allergenic source when all previous evaluations show no indication of allergenicity.
The detection of specific IgE antibodies in an individual does not necessarily mean the presence of a clinical allergy. Other factors may also determine whether an allergic reaction occurs, and those with IgE antibodies but no symptoms on exposure to the relevant allergen have “asymptomatic sensitivity”. In the case of food allergy, only 30% to 40% of individuals with IgE antibodies to foods will have allergic reactions on ingesting the food (Bock et al., 1988; Sampson, 1988). However, high levels of IgE antibodies do increase the probability of a clinical allergy.
The reliability of prick skin testing is clearly affected by the quality of the food allergen extract used. Prick skin tests to some foods, especially fruits and vegetables, must be performed with freshly prepared extracts due to the labile nature of the allergenic protein. Improper extraction of the food proteins may lead to inadequate concentrations of relevant allergens in the skin test extract, which results in false negative tests. Processing, heating or digestion of a protein can destroy protein antigenicity, but it can also enhance the allergenicity by formation of new epitopes or neonantigens. In these cases, allergy testing with the native food may also produce false negative results, which may explain some case reports of allergic reactions to sesame seeds without demonstrable IgE sensitization (Eberlein-Konig et al., 1995). This emphasizes the need in selected cases for food challenges (DBPCFC).
Animal models for in vivo testing may be useful in certain circumstances but there is no animal model currently able to predict accurately human allergic responses and therefore donor protein allergenicity. Examples of current animal models for allergy evaluation include mouse models to evaluate IgE responses to recombinant allergens, and guinea pig and rat models of anaphylaxis. The difficulties in using animal models to assess allergic potential have been documented (Metcalfe et al., 1996; Taylor and Lehrer, 1996; Kimber et al., 1999). An appropriate animal model of food allergy must be such that the test animal is able to mount a human-type IgE antibody response to foods under near natural conditions; that is, it must be able to mount a significant IgE antibody response to the food allergen in question, by the usual provocation route, oral exposure. At the same time, it must be able to tolerate the majority of food proteins. In addition, the animal’s allergic responses should be similar to those seen in humans, be consistent and easily reproducible. Unfortunately, no such model exists. Current animal models mount IgE responses only with difficulty, and under abnormal conditions such as induction by injection of the allergen together with adjuvant to enhance the immune response. Even in these models, the IgE responsiveness can vary at different times under the same conditions.
Use of animal models to screen for potential immunogenicity (ability to mount an immune response by producing IgG antibodies) and using this response as an indicator of potential allergenicity or ability to induce IgE has met with some significant failures with respect to human foods. Guinea pig and rabbit animal models were used to assess the allergenicity of partially hydrolysed cow’s milk whey formulas. These animal models predicted reduced immunogenicity of the whey hydrolysate formulas which were then marketed as “hypoallergenic”, but in fact they remained sufficiently allergenic to cause reactions in most cow’s milk-allergic infants (Palud et al., 1985; Taylor and Lehrer, 1996; Host et al., 1999; AAP, 2000). Assessment of the brazil nut albumin protein in transgenic soybean for potential allergenicity using a mouse model of passive cutaneous anaphylaxis did not elicit an allergic or immune response, leading to the erroneous conclusion that there was no allergenic protein transfer to the soybean (Astwood and Fuchs,1996b; Nordlee et al., 1996).
More reliable animal models mounting human-type IgE responses as described above have the potential to reduce the present dependence on human sera. These could be developed through standard breeding and selection, or perhaps even transgenically. Kleiner et al. (1999) and Li et al. (2000) have recently developed mouse models of cow’s milk allergy and peanut allergy.
Physicochemical CharacteristicsProtein allergens tend to have certain characteristics such as molecular weight between 10 and 70 kiloDaltons (kDa), and resistance to acid and proteolytic enzyme digestion (i.e. resistance to gastric digestion). They are usually proteins, often glycosylated (sugar compounds attached to the protein), are relatively stable to heating, have acid isoelectric points, are often water-soluble albumins or salt-soluble globulins, and usually make up a significant percent (1% to 80%) of the protein content of the source material (Matsuda and Nakamura, 1993; Astwood and Fuchs, 1996b; Bush and Heffle, 1996; Metcalfe et al., 1996). GM food proteins showing diagnostic physicochemical characteristics of allergens such as molecular weight, and stability to heat and gastric digestion may then be considered to have a higher potential for allergenicity, if direct immunologic assays are not available.
However, these are not particularly reliable indicators. There are a number of heat-labile or partially heat-labile food proteins which denature and lose conformational epitopes on heating, such as cow’s milk whey beta-lactoglobulin and bovine serum albumin, chicken egg ovomucoid, rice glutenin and globulin, soy glycinin and some peanut proteins (Matsuda and Nakamura, 1993; Bush and Hefle, 1996; Taylor and Lehrer, 1996). Similarly, while food allergens often constitute a significant portion of a food’s proteins, as mentioned previously, the potency of an allergen may compensate for its relative paucity in a food, and some major allergens such as codfish Gad c 1 are present only in small proportions of the food. Likewise, some protein allergens are low molecular weight such as the 9 kDa plant lipid transfer proteins (LTP) which are important allergens of the Prunoideae family which include peaches, plums and cherries (Breiteneder and Ebner, 2000; Rodriguez et al., 2000); LTP from barley used in beer foam formation (Curioni et al., 1999); and the 8 kDa soybean hull protein responsible for asthma outbreaks in Spain (Gonzalez et al., 1991). Interestingly, heating some allergenic proteins may actually increase their allergenicity, in some instances by chemical glycosylation (Maillard reaction). Examples include cow’s milk beta-lactoglobulin, pecan, fish, shrimp, snow crab and limpet (Malanin et al.,, 1995; Berrens, 1996; Taylor and Lehrer, 1996; Moneret-Vautrin, 1998).
It should be noted that some allergenic compounds are not proteins. Known examples are shrimp transfer RNA, inulin (a carbohydrate); and vegetable gums such as carrageenan and tragacanth (Danoff et al., 1978; Yeates, 1991; Tarlo et al., 1995; Bush and Hefle, 1996; Gay- Crosier et al., 2000). In addition, a large number of foods, in particular raw fruits, raw vegetables and spices, have heat-labile proteins (e.g. chitinases and Bet v 1) which cause the Oral Allergy Syndrome. All these exceptions would not be identified as allergens by their physicochemical criteria, or by any other criteria if they were present as a novel protein GM.
Prevalence of Allergy to the Donor ProteinIf the prevalence of an allergy to the donor protein is very low, then it may not be recognized or it may be very difficult to obtain sufficient amounts of sera from allergic persons to adequately test for the presence of allergens. Limited testing can lead to missed allergenic characteristics. Metcalfe and colleagues (1996) and Taylor (2000) have suggested that a lower standard of assurance of absence of allergen transfer be used where limited human sera is available for testing. However, this limitation could be overcome by establishing a registry and/or a bank of serum from allergic people.
Potential Changes in Host AllergenicityWhen a host organism is being genetically engineered, it must be ensured that the modified host organism has not undergone pleiotropic changes that result in creation of novel allergens. These effects could include the GMO being induced to express higher levels of its own endogenous allergens beyond what might be expected from natural variability; or endogenous or transgenic proteins undergoing post-translational modification including glycosylation or alteration of its 3D structure, perhaps changing allergenicity or creating new allergens. These possibilities can be assessed using the in vitro immunological assays described above. Such changes could increase the severity of an allergy reaction in persons already allergic to the host or donor food, and increase total dietary exposure to a more allergenic food.
Genetic engineering may affect endogenous allergen content in several ways, including altering the host plant metabolic pathways and enhancing allergen production. Storage, and effect of plant hormones such as ethylene, are known to increase the allergenicity of foods such as apple, banana and peach. Stress may also increase the levels of allergenic proteins (e.g. Bet v 1) in some fruits and vegetables (Hsieh et al., 1995; Pastorello and Ortolani, 1996; Breiteneder and Ebner, 2000; Rodriguez et al., 2000; Sanchez-Monge et al., 2000). Different varieties of foods such as peanut, avocado and wheat vary in their allergen content (Bush and Hefle, 1996) and these levels could conceivably be altered further by genetic modification.
Other Considerations in Allergenicity AssessmentSome factors may affect results of allergenicity evaluation, and may need to be considered in assessing or designing studies. The detection of clinically important food allergens may be complicated by the presence of cross-reactive allergens in the food. These cross-reactive allergens may show some similarity to the test allergenic protein and may give positive results, usually weakly, using in vivo and in vitro immunologic assays, but may not cause true allergic reactions. Botanically related plants may have cross-reactive allergens, examples of which are legumes such as peanut, peas, beans and soy. Thus, a peanut-allergic person may have IgE antibodies to peas but can eat peas without allergic reactions. Clusters of allergens also occur when distinct, nonbotanically related plants and foods share similar allergens, as in the birch/celery/spice syndrome, otherwise known as the Oral Allergy Syndrome, where individuals allergic to Bet v 1, the major allergen of birch pollen, also have allergic reactions to homologous pathogenesis-related proteins found in certain fruits, nuts, vegetables and spices (Halmepuro et al., 1984; Breiteneder and Ebner, 2000; Rodriguez et al., 2000). Another important food allergy cluster is the latex-fruit syndrome due to an allergy to Hev b 2, a pathogen-induced endoglucanase enzyme found in natural rubber latex but found also in avocado, banana, chestnut and kiwi (Moller et al., 1998; Breiteneder and Ebner, 2000).
Certain homologous proteins are also found in widely varying species such as tropomyosin in shrimp, chicken, mosquito, cockroach and housedust mites, although the cross-reactivity is probably low (Bush and Hefle, 1996). The degree of sequence homology is important. The major shrimp allergen, tropomyosin, is a protein present in many other foods including beef, pork and chicken with which it shares 60% sequence homology, but beef, pork and chicken tropomyosin are rarely allergenic (Lehrer et al., 1996). In these cases, a definitive answer regarding allergenicity can only be based on specific IgE-based assays.
Some food allergies, such as those involved in the Oral Allergy Syndrome, produce allergenic effects on the oral mucosa during mastication of the food. Oral challenges with these foods by swallowing (e.g. in capsule form as is the preferred method for DBPCFC rather than chewing) may not reproduce the allergic reactions seen in the real-life process of chewing and eating. Foods normally eaten cooked but which may occasionally be handled or eaten raw (e.g. potato) may show a different allergenicity profile depending on how the food is presented for oral challenge. The converse situation also needs to be considered (i.e. foods which increase their allergenicity on heating).
If an allergen is expressed in the host organism, the site of expression such as in the leaves, pollen or edible part of the plant is important in considering risk. There would be different implications if the allergen is not expressed in the edible but rather in the non-edible portion of the plant, or if the allergenic plant proteins might be inhaled during processing of plant parts with the accompanying risk of occupational sensitization.
An Example of the Evaluation Process to Assess AllergenicityA useful model to examine is the evaluation process used by the US Environmental Protection Agency (USEPA) for potential allergenicity of the Cry9C gene from Bt encoding for an insecticidal crystal protein endotoxin, inserted into GM corn, using the criteria described above (USEPA, 1999a, b). The USEPA used an approach developed during the 1994 Interagency Conference on potential allergenicity in transgenic food crops, which included the USEPA, Food and Drug Administration, and Department of Agriculture (Fox, 1994; USEPA, 1999a). They evaluated the source of the donor gene, which had no known allergenic history despite 30 years of use as a microbial insecticide. However, Bt is not a food product, and this particular BT gene had been modified and therefore had a much shorter exposure history. Comparison with known allergens showed no epitope sequence homology and therefore no resemblance. Immunologic analysis was limited by the absence of material from humans clinically allergic to BT since none has been identified. A brown Norway rat model of IgE immune response was inconclusive although an immune response was provoked. Physicochemical characteristics showed that the Cry9C protein did show some stability to simulated gastric fluid digestion and some heat stability. In addition, its molecular weight of 68.7 kDa fell at the upper end of the range for allergen molecular weight. These physicochemical characteristics suggested a potential for allergenicity, although it was present at a low level (0.17% of total weight), features not usually seen with important allergens. Potential pleiotropic effects were examined by screening the genetically altered Cry9C corn with serum from suspected corn-reactive subjects, which did not detect any alterations in the intrinsic allergenic status of the GM corn.
On the basis of two positive biochemical characteristics found in allergens (relative stability to heat and gastric digestion), the USEPA declined to upgrade Cry9C Bt corn for use as human food in 1999 and left unchanged the approval as an animal feed and for industrial use. Other Bt genes encoding similar endotoxins (e.g. Cry1A and Cry3A) have been approved for human consumption in GM corn and potato as they did not demonstrate the biochemical characteristics shown by the Cry9C gene product, nor did they exhibit any other signs to indicate potential allergenicity (USEPA, 1995).
Unfortunately, the Cry9C corn (termed StarLink (TM)) inadvertently contaminated corn destined for human use resulting in a large recall of corn-derived food products in the US in October 2000. In addition, Cry9C protein was discovered in some non-StarLink seed corn, and although this was felt to be due to physical contamination, cross pollination from StarLink corn could not be ruled out as the source. The accidental introduction of StarLink corn into the human food chain prompted a further review of the potential allergenicity of Cry9C, and of mechanisms for assessing suspected allergenic reactions to StarLink corn. This review was conducted by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP), the primary scientific peer review mechanism of the USEPA (FIFRA, 2000; US EPA, 2000a).
FIFRA-SAP concluded that the Cry9C protein had a medium likelihood of proving to be a potential allergen. They considered that at least 7 of 34 complaints regarding reactions to a corncontaining meal were probably allergic, based on a careful assessment of the history which was compatible with a food allergy, plus opportunity for exposure to the suspected protein, as well as confounding factors (e.g. other allergens). In the final analysis, the determination of whether an allergic reaction occurred to the Cry9C protein in StarLink corn would have to be based on detection of the Cry9C protein in the ingested food, detection of antibodies, especially IgE to Cry9C protein in the subjects’ serum, and if necessary oral food challenge (DBPCFC).
At the strong urging of the USEPA, StarLink corn was voluntarily withdrawn from agricultural use, and all known existing corn contaminated with it has been restricted for nonhuman food use (USEPA, 2000b). Unaccounted StarLink corn could continue to enter the food supply over the next few years, however. This incident underscored the difficulty of restricting a GM food for animal/industrial use when almost indistinguishable non-GM food counterparts are simultaneously available for human consumption. It also highlights the issue of mandatory labelling (discussed in Chapter 9, Part 2). Post-introduction surveillance of a GM food which has medium to high-risk allergenic potential is essential. This medium- to high-risk scenario must be accompanied by appropriate labelling to identify allergic reactions rapidly and accurately. However, where the risk of allergenicity is low, the justification for labelling diminishes from a scientific viewpoint, bearing in mind that the lack of labelling can lead to delayed recognition of the emergence of an allergy, with consequent under-reporting. Therefore, especially when labelling is not required, there should be mechanisms to record, evaluate and fully investigate complaints of suspected allergy, as recommended above for StarLink corn by FIFRA-SAP. In addition, since there may be potential exposure to multiple unlabelled GM proteins from different sources, evaluation of the subjects may have to include a battery of dietary GM proteins.
It could be argued that requiring GM proteins and GM foods to undergo rigorous assessment for allergenicity prior to approval as a food product, with or without labelling, represents a double standard since this process is not required when a novel or exotic non-GM food is introduced. An exotic food may still pose a risk because while there is some history of previous consumption, it may not have been extensive or monitored sufficiently to ensure its safety, and the genetic susceptibility to allergies in its native area may differ. On the other hand, the presence of an exotic or novel food in the diet is more easily identifiable, avoidable, and more easily monitored for the possibility of adverse reactions, compared to a transgenic protein in a food which may not be easily monitored as regards degree and frequency of exposure, or even whether exposure has occurred at all.
Notwithstanding the limits of current technology, a GM food which has undergone a thorough, scientifically valid evaluation process for allergenicity, with negative results, should be considered at low risk to provoke or induce allergic responses and could possibly even be safer than a non-GM novel or exotic food which has not been subjected to the same scrutiny. This evaluation process can significantly minimize allergenicity concerns and perhaps reduce the chances of GM products being used as scapegoats for a variety of real or perceived illnesses. It stands to reason that any GM food with potential or identified allergenicity must either not be approved for human consumption, or if approved, then it must be appropriately labelled.
SummaryThe identification of potential allergens in GMOs is accurate and reliable when assessing transgenes from known allergenic sources. It is indirect and non-specific with respect to novel proteins from sources not known to be allergenic and without a history of extensive human exposure. Even for the nine identified major food allergens responsible for most of the severe allergic reactions to foods in Canadians, only some of the allergens have been chemically characterized, and none has been standardized. In vivo and in vitro techniques are available to assess accurately and reliably potential allergenicity when dealing with proteins from known allergenic sources. Where the donor gene comes from an organism not known to be allergenic, or of unknown allergenicity (e.g. an exotic food, or a product not normally ingested as food), assessment becomes more difficult. There is currently no single assay or combination of assays that will accurately predict the allergenic potential of protein from sources not known to be allergenic. Nevertheless, using an array of properly designed and executed assays, and knowledge regarding the characteristics of the transgene, a GM food may then be considered relatively safe for allergic consumers and comparable to its non-GM counterpart, if all tests are negative. Not withstanding negative allergenicity assessments, however, if the transgene is derived from a source of unknown allergenicity, post-introduction surveillance may be prudent to monitor for any unanticipated allergic effects, recognizing that this may be more difficult without corresponding labelling of GM foods.
RECOMMENDATIONS4.4 The Panel recommends that the Canadian government should support research initiatives to increase the reliability, accuracy and sensitivity of current methodology to assess allergenicity of a food protein, as well as efforts to develop new technologies to assist in these assessments. This would include further research into the identification, purification, characterization and standardization of common food allergens, as well as their respective antibodies (e.g. monoclonal animal antibodies) which can be used in detection systems; development of reliable animal models of human-type IgE antibody responses; identification of specific characteristics which can accurately and specifically identify a novel protein as being allergenic; and development of rapid assays (e.g. dipstick-type assays) for use by food processors and consumers to detect allergenic contaminants.
4.5 The Panel recommends the strengthening of infrastructures, and where none exists, development of these infrastructures to facilitate evaluation of the allergenicity of GM proteins. This could include development of a central bank of serum from properly screened individuals allergic to proteins which might be used for genetic engineering, a pool of standardized food allergens and the novel GM food proteins or the GM food extracts, maintenance and updating of allergen sequence databases, and a registry of food-allergic volunteers. These would enhance the ability of government agencies such as the Canadian Food Inspection Agency to broaden the scope of and its technological ability to detect allergenic proteins.
4.6 The Panel recommends development of mechanisms for after-market surveillance of GM foods incorporating a novel protein, if there are data to indicate its effectiveness, to detect the emergence of consumers developing allergies to such a food either through increase in total dietary exposure over the long term, or occurrence of unanticipated and unpredicted allergic reactions. This could include a central reporting registry and/or epidemiological studies to assess changes in frequency, pattern and clinical presentations of allergy-related complaints. The infrastructure in Recommendation 4.5 could be used to verify scientifically reports of allergic reactions and detect emergence of allergies to GM proteins.
4.7 The Panel recommends that the appropriate government regulatory agencies have in place a specific, scientifically based, comprehensive approach for ensuring that adequate allergenicity assessment will be performed on a GM food, utilizing currently available techniques combined with currently available knowledge of the characteristics of the GM protein relevant to potential allergenicity, and updating testing requirements in keeping with new technologies. Any decision not to complete a full and comprehensive allergenicity assessment should be made only after careful consideration of the scientific rationale to support that omission. The decision to approve or not approve introduction of a GM food and the need for labelling should therefore be based on a rigorous scientific rationale.
4.8 The Panel recommends that approvals should not be given for GM products with human food counterparts that carry restrictions on their use for non-food purposes (e.g. crops approved for animal feed but not for human food). Unless there are reliable ways to guarantee the segregation and recall if necessary of these products, they should be approved only if acceptable for human consumption. If a GM food is found to have acquired additional allergenic properties from gene transfer, then that GM food should either not be marketed, or be properly labelled if marketed
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PART 3. NUTRITION ISSUES
IntroductionA central concern in any modification of traditional food sources must be the impact of such changes on the nutrient content of the food. The components generally considered under this rubric are the content of carbohydrates (simple and complex), proteins and their constituent amino acids, fats and their fatty acid profiles, vitamins, dietary fibre and anti-nutrients. No crop species, in itself, provides an appropriately balanced range of nutrients for human or animal consumers. A diet that effectively meets metabolic needs, therefore, must be derived from multiple sources that complement each other’s nutrient strengths and deficiencies. Nutritionists, dietitians and food specialists work with databases such as the Canadian Nutrient File, which are designed to reflect the average amounts of nutrients in individual foods. Based on such data, which are derived from the history of the commercially grown varieties as a food source, a common crop (e.g. potatoes or corn) would be expected to provide certain nutrients within a known range. If the concentration of a particular nutrient happened to fall at or beyond the extremes of the range, there could be health implications, particularly for humans who rely heavily on that foodstuff in their diet.
Another nutritional parameter that normally attracts regulatory attention is the level of specific anti-nutrients in some foodstuffs. While the definition of an anti-nutrient remains unclear, the term generally refers to plant secondary metabolites that appear to have deleterious effects over time on animal or human consumers. Examples of anti-nutrients whose levels are usually monitored in new Canadian crop varieties include erucic acid and glucosinolates in canola, cyanogenic glycosides in flax, and glycoalkaloids in potatoes.
Impacts of Genetic EngineeringGenetic engineering of common crops in Canada has thus far not focused on nutrient modification, and any impacts on the major nutrients in these first generation GM crops would presumably have to be the result of pleiotropic effects of the transgene(s). To date, GM foods produced from approved GM crops have been judged to be nutritionally equivalent to their non- GM counterparts, presumably on the basis of chemical analyses for the classes of nutrients described above. However, the Panel is unaware of any public data available for confirmation of this assumption. In fact, the only nutritional information related to GM foods available to the public appears in the Decision Documents released by the CFIA for animal feeds (CFIA, Plant Biotechnology Decision Documents, at:
www.cfia-acia.ca/english/plaveg/pbo/isda01_.html). This is restricted to a statement about proximate analysis (an unsophisticated procedure that analyzes the material for crude protein, crude fat, ash and moisture levels) and in some cases examines certain groups of amino acids, together with the comment that anti-nutrients did not exceed acceptable levels.
New GM varieties specifically designed to present altered profiles of fatty acids, altered starch qualities, and/or altered protein profiles are all currently under development. Some of the proposed changes have the potential to improve the foodstuff’s nutritional quality, such as GM corn whose storage proteins contain an enhanced level of lysine, the limiting amino acid in that food. Other nutritional modifications being explored include increased vitamin content (e.g. carotenoids, a source of vitamin A – as in “golden rice”), higher iron content, and enhanced concentrations of nutraceuticals such as lignans and bioflavonoids (antioxidants). This ability to fortify traditional foodstuffs is expected to be marketed as a direct consumer benefit of GM foods. While positive impacts can be envisioned, any substantial alteration of food nutrient profiles has potential ramifications that would appear to call for careful monitoring and public reporting.
TestingChemical analysis provides the first level of assessment of possible changes in nutrient content in novel foods. Very powerful methodologies are now available for analysis of protein, fatty acid and carbohydrate profiles, as well as scanning for changes in secondary metabolite profiles (see Chapter 7). Nevertheless, food is a complex material with many potential interactions among its components that would be hard to predict simply by scoring the individual chemical classes. Where significant deviations from the profile ranges expected for a food component are detected, it may therefore be desirable to conduct whole organism tests designed to assess nutrient bioavailability. This is analogous to the need, discussed earlier in this chapter, to determine whether novel foods bring with them any new toxicological risks.
The assessment could involve either animal testing, where a suitable animal model has been developed, or testing in human subjects. A foodstuff could be tested as part of a diet fed to experimental animals, which could then be monitored for health and growth over their normal lifetime. Where chemical analysis has detected changes in particular food components, it may be more useful to examine the impacts of those changes by using the specific component as a dietary ingredient. Proteins have been evaluated in this fashion in experimental animals for at least four decades (Campbell and Chapman, 1959). In the early tests done in rats, protein was 10% by weight of the diet and the duration of the feeding was four weeks. A faster method, which gives similar results and involves using an amino acid profile corrected for the digestibility of the protein, took no more than two weeks (Sarwar and McDonough, 1990). This method has been adopted by the FAO/WHO Expert Consultation (1991) on protein quality evaluation. Suitable tests should be available for evaluating specific fat and/or carbohydrate compositions, while testing the impacts of discrete anti-nutrients would follow the well-established protocols developed for toxicological testing.
Human foods differ from animal feeds in that the emphasis is less on rapid weight gain in a shortened life span, or on enhanced milk production, and more on a long, healthy life as free as possible from disease. Over the many decades of human life, foods are expected to provide all recognized nutritional requirements. Relatively short-term animal tests may yield valuable information, but establishing the impacts of long-term ingestion of a food would involve the systematic monitoring of human populations. This issue is clearly related to the question of labelling of GM foods, and has been explored in Chapter 9 of this Report.
RECOMMENDATIONS4.9 The Panel recommends that all assessments of GM foods, which compare the test material with an appropriate control, should meet the standards necessary for publication in a peerreviewed journal, and all information relative to the assessment should be available for public scrutiny. The data should include the full nutrient composition (Health Canada, 1994), an analysis of any anti-nutrient, and where applicable, a protein evaluation such as that approved by FAO.
4.10 The Panel recommends that protocols should be developed for the testing of future GE foods in experimental diets.
4.11 The Panel recommends that the Canadian Nutrient File should be updated to include the composition of GE foods and be readily available to the public.
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FAO/WHO Expert Consultation. 1991. Protein Quality Evaluation. Rome.
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Sarwar, G., F.E. McDonough. 1990. Evaluation of protein digestibility-corrected amino acid score for evaluating protein quality of foods. J. Assoc. Official Anal. Chem. 73: 347–56.