Genetically Engineered Crops Experiences and Prospects (2016) / Chapter Skim
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5 Human Health Effects of Genetically Engineered Crops
5 Human Health Effects of Genetically Engineered Crops
Pages 171-254
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From page 171... ...
Some of the evidence available to the committee came from documents that were part of the U.S. regulatory process for GE crops conducted by the U.S.
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From page 172... ...
"Bioengineered foods have been consumed for close to 20 years, and during that time, no overt consequences on human health have been reported and/ or substantiated in the peer-reviewed literature." Council on Science and Public Health (2012) "[Genetically modified]
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From page 173... ...
A variety of hypothesized health risks posed by and benefits of GE crops are examined, and the chapter concludes with a short discussion of the challenges that society will face in assessing the safety of GE foods that are likely to be developed with emerging genetic-engineering technologies. COMPARING GENETICALLY ENGINEERED CROPS WITH THEIR COUNTERPARTS An oft-cited risk of GE crops is that the genetic-engineering process could cause "unnatural" changes in a plant's own naturally occurring proteins or metabolic pathways and result in the unexpected production of toxins or allergens in food (Fagan et al., 2014)
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From page 174... ...
. Plant secondary metabolites that protect against pathogen attack have been classified as either phytoanticipins (if they exist in a preformed state in a plant before exposure to a pathogen)
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Unintended changes in the concentrations of secondary metabolites can result from conventional breeding (Sinden and Webb, 1972; Hellenas et al., 1995)
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From page 176... ...
. The Codex Alimentarius Commission's Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants is careful to state that "the concept of substantial equivalence is a key step in the safety assessment process.
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From page 177... ...
. Two general sources of unintended differences could affect food safety: • Unintended effects of the targeted genetic changes on other char acteristics of the food (for example, the intended presence of or increase in one compound in plant cells could result in changes in plant metabolism that affect the abundance of other compounds)
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From page 178... ...
FINDING: The concept of substantial equivalence can aid in the iden tification of potential safety and nutritional issues related to intended and unintended changes in GE crops and conventionally bred crops. FINDING: Conventional breeding and genetic engineering can cause unintended changes in the presence and concentrations of secondary metabolites.
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From page 179... ...
Furthermore, there have been claims and counter claims about the relative safety of GE crops and their associated tech nologies compared with conventionally bred crops and their associated technologies. Therefore, the remainder of this chapter examines possible risks and benefits associated with GE crops and assesses the methods used to test them in and beyond government regulatory systems.
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From page 180... ...
. The pesticidal safety tests mostly involved acute toxicity testing in mice and digestibility studies in simulated gastric fluids because one characteristic of food allergens is that they are not rapidly digested by such fluids.
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From page 181... ...
Current scientific knowledge suggests that common food allergens tend to be resistant to degradation by heat, acid, and proteases, may be glycosylated and present at high concentrations in the food. "Data has been submitted which demonstrates that the Cry1F protein is rapidly degraded by gastric fluid in vitro and is non-glycosylated.
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From page 182... ...
. • A chronic-dietary-endpoint, extended one-generation reproduction toxicity study in rats that found a LOAEL of 46.7 mg/kg-day in females and higher in males.
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From page 183... ...
, minerals, amino acids, fatty acids, and vitamins. No statistically signifi cant differences in the overall treatment effect and the paired contrasts between each of the DAS-44406-6 soybean treatment groups and the control were observed for 29 of the components.
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From page 184... ...
As can be seen in the discussion above, EPA conducted an extended one-generation reproduction toxicity study in male and female rats in its assessment of 2,4-D, and it relied on previous long-term studies for the assessment of cancer risk associated with it. For assessment of the Bt toxin Cry1F and for the bacterially derived proteins in 2,4-D-resistant maize and soybean, company testing submitted to EPA, FDA, and USDA relied on acute toxicity testing.
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From page 185... ...
, the European Directorate-General for Research and Innovation concluded that "the data from a well-designed 90-day rodent feeding study, together with data covering the gene insert, the compositional analysis, and the toxicity of the novel gene product, form the optimal basis for a compara tive assessment of the safety of [genetically engineered] food and its con ventional counterpart in the pre-market situation" (EC, 2010a:157)
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From page 186... ...
In an acute toxicity study, the animals are given a wide range of doses to establish the signs of toxicity that may be observed in subacute and subchronic (28-day and 90-day) rodent studies (FDA, 2000a, revised 2007)
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. A general question that remains for all whole-food studies using animals is, How many animals, tested for how long, are needed to assess food safety when a whole food is tested?
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In the notice, the editor-in-chief explained that "the results presented (while not incorrect) are inconclusive, and therefore do not reach the threshold of publication for Food and Chemical Toxicology"; he also made clear that "the Editor-in-Chief wishes to acknowledge the co-operation of the corresponding author in this matter, and commends him for his commitment to the scientific process.
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From page 189... ...
feeding trials need to be conducted to thoroughly evaluate the safety of [GE] foods and pesticides in their full commercial formulations." The comment on the original paper by the editor-in-chief of Food and Chemical Toxicology that "the results presented (while not incorrect)
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From page 190... ...
at doses of 11 per cent, 22 percent, and 33 percent of their diet (thin, medium, and bold lines, respec tively) and compared with closest isogenic non-GE maize control (dotted line)
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HUMAN HEALTH EFFECTS OF GENETICALLY ENGINEERED CROPS 191 studies with much larger samples be conducted to determine whether there is reason to use 2-year studies generally, but the committee disagrees that this one study should lead to a general change in global procedures regarding the health effects and safety of GE crops. Many of the published criticisms of the Séralini et al.
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From page 192... ...
factorial design. Because the relationship is quite abstract for the nonstatistician, the committee examined the size of the standard deviations in a number of whole-food safety articles.
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per treatment. Following these guidelines leads to the assumption that less than a 25-percent change in the white blood cell count was not biologically relevant.
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From page 194... ...
There was no presentation of standards used for judging what would be a biologically relevant difference or for what the normal range was in the measurements. The standard deviations in measurements of the traits (that is, effects)
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From page 195... ...
In cases in which testing produces equivocal results or tests are found to lack rigor, follow-up experimentation with trusted research protocols, personnel, and publication outlets is needed to decrease uncertainty and increase the legitimacy of regulatory decisions. There is a precedent of such follow-up studies in the literature on GE crop environmental effects that could serve as a general model for follow-up food-safety testing (see Chapter 4 section "Genetically Engineered Crops, Milkweed, and Monarch Butterflies")
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From page 196... ...
In those experiments with pigs and experiments with other farm animals and rodents, there was apparently one source of the GE food and one source of the non-GE food per study, and it is generally not clear that the food sources were isogenic or grown in the same location. That makes it difficult to determine whether any statistical differences found were due to the engineered trait or to the batches of food used, which in at least some experiments varied in nutrient content and may have differed in bioactive compounds (produced in response to plant stressors)
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From page 197... ...
RECOMMENDATION: Before an animal test is conducted, it is im portant to justify the size of a difference between treatments in each measurement that will be considered biologically relevant. RECOMMENDATION: A power analysis for each characteristic based on standard deviations in treatments in previous tests with the animal species should be done whenever possible to increase the probability of detecting differences that would be considered biologically relevant.
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From page 198... ...
They were therefore "considered not biologically relevant." In compositional analysis, as in some of the whole-food animal testing, it is difficult to know how much of the variance and range in values for the components is due to the crop variety, the growing conditions, and the specific laboratory experimental equipment. In the United States, regulatory agencies require that the comparison be between the GE crop and its isogenic conventionally bred counterpart grown in side-by-side plots.
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From page 199... ...
. The detection of GE protein and DNA in other processed foods depends on the type of processing.
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From page 200... ...
(2008) found that three free amino acids, an amino acid precursor, and flavonoid-derived secondary metabolites (liquiritigenin, naringenin, and taxifolin)
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From page 201... ...
Chapter 7 addresses the future utility of the -omics approaches in assessing the biological effects of genetic engineering. FINDING: In most cases examined, the differences found in com parisons of transcriptomes, proteomes, and metabolomes in GE and non-GE plants have been small relative to the naturally occurring variation found in conventionally bred crop varieties due to genetics and environment.
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From page 202... ...
Endogenous protein concentrations with known allergic properties also have to be monitored because it is possible that their concentration could increase due to genetic engineering. A flow diagram of the interactive approach to allergen testing recommended by the Codex Alimentarius Commission (CAC, 2009)
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From page 203... ...
research demonstrating that some, but not all, proteins already known to be food allergens are resistant to digestion by gut fluid. There is one case in which that approach was used and a GE crop with allergenicity issues was detected early and prevented from being commercialized, and a second case in which a GE crop was withdrawn from the market based on the possibly that it included a food allergen.
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From page 204... ...
. The testing does not cover endogenous allergens whose concentrations have been increased by unintended effects of genetic engineering.
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. There is one patent for decreasing gamma-zein through genetic engineering.5 There can be a connection between immune response and a llergenicity.
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From page 206... ...
FINDING: For crops with endogenous allergens, knowing the range of allergen concentrations in a broad set of crop varieties grown in a variety of environments is helpful, but it is most important to know whether adding a GE crop to the food supply will change the general exposure of humans to the allergens.
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From page 207... ...
GENETICALLY ENGINEERED CROPS AND OCCURRENCE OF DISEASES AND CHRONIC CONDITIONS The overall results of short-term and long-term animal studies with rodents and other animals and other data on GE-food nutrient and secondary compound composition convinces many (for example, Bartholomaeus et al., 2013; Ricroch et al., 2013a,b; Van Eenennaam and Young, 2014) but not all involved researchers (for example, Dona and A rvanitoyannis, 2009; Domingo and Bordonaba, 2011; Hilbeck et al., 2015; also see DeFrancesco, 2013)
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From page 208... ...
For that reason, the committee sought data on cancer incidence rather than cancer mortality. Figures 5-4 and 5-5 show FIGURE 5-4 Trends in cancer incidence in women in the United States, 1975–2011.
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(2011) published data on breast and cervical cancer incidence worldwide from 1980 to 2010.
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FIGURE 5-7 Cancer incidence in men in the United Kingdom, 1975–2011. DATA SOURCE: Cancer Research UK.
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: Canada, United States; Western Europe: Andorra, Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, Malta, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom. Dashed line at 1996 indicates year genetically engineered soybean and maize were first grown in the United States.
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From page 212... ...
Taken together, Figure 5 through Figure 8 do not support the h ypothesis that GE foods have resulted in a substantial increase in the incidence of cancer. However, they do not establish that there is no relationship between cancer and GE foods because there can be a delay in the onset of cancer that would obscure a trend, and one could hypothesize that something else has occurred with GE foods in the United States that has lowered cancer incidence and thus obscured a relationship.
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From page 213... ...
FINDING: The incidence of a variety of cancer types in the United States has changed over time, but the changes do not appear to be associated with the switch to consumption of GE foods. Furthermore, patterns of change in cancer incidence in the United States are gener ally similar to those in the United Kingdom and Europe, where diets contain much lower amounts of food derived from GE crops.
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FIGURE 5-9 Prevalence of chronic kidney disease by stage among National Health and Nutrition Examination Survey (NHANES) participants, 1988–2012.
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From page 215... ...
rates of obesity or type II diabetes. Gastrointestinal Tract Diseases Although the gastrointestinal tract has evolved to digest dietary proteins in the stomach and small intestine effectively for absorption and use of amino acids, it is normal for some full proteins or their fragments to cross the gut barrier through a paracellular route (between cells)
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From page 216... ...
Dashed line at 1996 indicates year genetically engineered soybean and maize were first grown in the United States. of a dietary protein or its fragment in the bloodstream or in tissues is not unusual or a cause for health concerns.
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From page 217... ...
. In addition to exposure to gluten, the etiology of celiac disease is multifactorial and includes genetic predisposition, microbial infection of the gastrointestinal tract, antibiotic exposure, and gastrointestinal erosion (Riddle et al., 2012)
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The data are not robust, but they do not show a major difference in the rate of increase in incidence of celiac disease between the two countries.
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From page 219... ...
. FINDING: The committee did not find a relationship between consumption of GE foods and the increase in prevalence of food allergies.
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From page 220... ...
Green = ages 0–14 years; blue = ages 15–44 years; red = ages 45+ years. Dashed line at 1996 indicates year genetically engineered soybean and maize were first grown in the United States.
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From page 221... ...
OTHER HUMAN HEALTH CONCERNS RELATED TO GENETICALLY ENGINEERED CROPS The committee heard from some members of the public and some invited speakers that ailments of gastrointestinal origin could be caused by GE crops or their associated technologies or by foods derived from GE crops. The committee investigated the evidence available for that hypothesis.
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From page 222... ...
There were other inconsistent differences in mostly low abundance microorganisms. On the basis of the overall results from their studies, the authors concluded that none of the changes seen in the animals was expected to have biologically relevant health effects on the animals.
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From page 223... ...
A prerequisite for horizontal gene transfer is that the recombinant DNA must survive the adverse conditions of both food processing and pas sage through the gastrointestinal tract. Netherwood et al.
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From page 224... ...
FINDING: On the basis of its understanding of the process required for horizontal gene transfer from plants to animals and data on GE organisms, the committee concludes that horizontal gene transfer from GE crops or conventionally bred crops to humans does not pose a substantial health risk. Transfer of Transgenic Material Across the Gut Barrier into Animal Organs Conflicting reports exist regarding the question of intact transgenes and transgenic proteins from foods crossing the gut barrier.
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From page 225... ...
OVERALL FINDING ON PURPORTED ADVERSE EFFECTS ON HUMAN HEALTH OF FOODS DERIVED FROM GE CROPS: On the basis of detailed examination of comparisons of currently com mercialized GE and non-GE foods in compositional analysis, acute and chronic animal-toxicity tests, long-term data on health of livestock fed GE foods, and human epidemiological data, the committee found no differences that implicate a higher risk to human health from GE foods than from their non-GE counterparts. ASSESSMENT OF HUMAN HEALTH BENEFITS FROM GENETICALLY ENGINEERED CROPS There are now a number of examples of crops, either commercialized or in the pipeline toward commercialization, that have GE traits that could improve human health.
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From page 226... ...
. The most rigorous assessments of the effects of those high–beta-carotene varieties were conducted with orange-fleshed sweet potato (high in beta-carotene)
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From page 227... ...
. Golden Rice, which was produced through genetic engineering to increase beta-carotene content, is one of the most recognized examples of the use of genetic-engineering technology to improve a crop's nutritional value.
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From page 228... ...
If Golden Rice is found to be safe and efficacious, a sustainable delivery program will ensure that Golden Rice is acceptable and accessible to those most in need."8 Increasing concentrations of beta-carotene is only one goal of conventional crop breeding and genetic engineering. Projects for increasing iron and zinc in crops as different as wheat, pearl millet (Pennisetum glaucum)
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From page 229... ...
, known in Europe as rapeseed, is the major oilseed crop in Canada. Canola was developed through conventional breeding at the University of Manitoba, Canada, by Downey and Stefansson in the early 1970s and had a good nutritional profile -- 58-percent oleic acid and 36-percent polyunsaturated fatty acids -- in addition to low erucic acid and a moderate concentration of saturated fatty acid (6 percent)
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From page 230... ...
The study used Syrian golden hamsters instead of rats because the hamsters are very sensitive to the glycoalkaloids. There were some statistically significant differences, but they were considered not of biological relevance.
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From page 231... ...
However, GE plants that indirectly or directly reduce fungal-toxin production and intake would offer substantial benefits to some of the world's poorest populations, which have the highest dietary intake of food-associated fungal toxins. Health Effects of Farmer Exposure to Insecticides and Herbicides Chapter 4 presents data that demonstrate substantially lower use of insecticides in some Bt crops than in conventionally bred crops.
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From page 232... ...
(2015:15) , who carefully assessed each of the studies, found many shortcomings that led them to conclude that "the link between [genetically modified]
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From page 233... ...
ASSESSMENT OF FOOD SAFETY OF CROPS TRANSFORMED THROUGH EMERGING GENETIC-ENGINEERING TECHNOLOGIES Increased Precision and Complexity of Genetic-Engineering Alterations At the time that the committee wrote its report, major commercialized GE crops had been engineered by using Agrobacterium tumefaciens- mediated or gene gun-mediated transformation, both of which result in semirandom insertion of the transgene into the genome. Variation in expression of the transgene was routinely observed because of the specific genomic characteristics of the insertion sites.
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From page 234... ...
Those projects are discussed further in Chapter 8. Although the precision of future geneticengineering alterations should decrease unintended effects of the process of engineering, the complexity of the changes in a plant may leave it not substantially equivalent to its non-GE counterpart.
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From page 235... ...
From a food-safety perspective, the increase in crops and traits presents a number of challenges. First is the need to develop better and more de tailed baseline data on the general chemical composition and probably the transcriptomic profiles of currently marketed conventionally bred varieties of the crops (see Chapter 7)
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From page 236... ...
RECOMMENDATION: There is an urgent need for publicly funded research on novel molecular approaches for testing future products of genetic engineering so that accurate testing methods will be available when the new products are ready for commercialization. CONCLUSIONS The committee's objective in this chapter was to examine the evidence that supports or negates specific hypotheses and claims about the risks and benefits associated with foods derived from GE crops.
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From page 237... ...
2013. The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recom mendations.
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From page 238... ...
2011. Performance of lactating dairy cows fed corn as whole plant silage and grain produced from genetically modified corn containing event DAS-59122–7 compared to a nontransgenic, near-isogenic control.
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2013a. Sequence-based analysis of the intestinal Micro biota of sows and their offspring fed genetically modified maize expressing a truncated form of Bacillus thuringiensis Cry1Ab protein (Bt Maize)
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2013. Comments on "Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize." Food and Chemical Toxicology 53:443–444.
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Presentation to the National Academy of Sciences' Committee on Genetically Engineered Crops: Past Experi ence and Future Prospects, September 16, Washington, DC.
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From page 242... ...
2003. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study.
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From page 243... ...
Presentation to the National Academy of Sciences' Committee on Genetically Engineered Crops: Past Experience and Future Prospects, March 5, Washington, DC.
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From page 244... ...
2014. Endogenous allergens in the regulatory assessment of genetically engineered crops.
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From page 245... ...
Presen tation to the National Academy of Sciences' Committee on Genetically Engineered Crops: Past Experience and Future Prospects, September 16, Washington, DC.
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From page 246... ...
2007. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.
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2012. A 90-day subchronic feeding study of genetically modified maize expressing Cry1Ac-M protein in Sprague–Dawley rats.
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2000. Substantial equivalence of antinutritional and in herent plant toxins in genetically modified novel foods.
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From page 249... ...
2005. Multigenerational reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats.
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From page 250... ...
2014. Presentation to the National Academy of Sciences' Committee on Geneti cally Engineered Crops: Past Experience and Future Prospects, September 16, Washington, DC.
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Presentation to the National Academy of Sciences' Committee on Genetically Engineered Crops: Past Experience and Future Prospects, September 16, Washington, DC. Snell, C., A
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2008. A three-year longitudinal study on the effects of a diet containing genetically modified Bt176 maize on the health status and performance of sheep.
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From page 253... ...
Presentation to the National Academy of Sciences' Committee on Genetically Engineered Crops: Past Experi ence and Future Prospects, December 10, Washington, DC.
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From page 254... ...
2014. Frequently Asked Questions on Genetically Modified Foods.
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