Safety Assessment of Biotech Foods

Food manufacturers are required by law to ensure the safety and quality of their products regardless of the source or identity of the ingredients. The Food and Drug Administration (FDA) views traditional foods as safe based on a long history of use.

Products derived through rDNA biotechnology are assessed for safety before their introduction into the food marketplace. Food manufacturers also must ensure the safety and quality of products that contain ingredients derived from rDNA biotechnology. In 1992, FDA provided a general outline for the safety assessment of rDNA biotechnologyderived food products based on risk analysis related to the characteristics of the products.

All of the existing foods produced using rDNA biotechnology have undergone a rigorous science-based safety assessment focusing on the characteristics of the products, especially the unique components. Thus, in practice, the safety assessment of foods derived using rDNA biotechnology has been more stringent than for conventionally derived products.

Substantial Equivalence

In the safety assessment of rDNA biotechnology-derived foods, it is helpful to compare the new plant variety to its traditional counterpart because the counterpart has a history of safe use as a food. The concept of substantial equivalence effectively focuses the scientific assessment on potential differences that might present safety or nutritional concerns.

Substantial equivalence is not an absolute determinant of safety per se, since compositional changes in an rDNA biotechnology- derived food may have no impact on the safety of the food. However, substantial equivalence provides a process to establish that the composition of the plant has not been changed in such a way as to introduce any new hazards into the food, to increase the concentration of inherent toxic constituents, or to decrease the customary content of nutrients. Key constituents measured include nutrients, such as proteins, fats, carbohydrates, vitamins, and minerals, as well as inherent antinutritional factors, toxins, and allergens. For example, high-oleic-acid soybean oil from rDNA biotechnology-derived soybeans has an oleic acid concentration that falls outside the range typically found in soy oils. From a scientific perspective, this food is nevertheless considered safe, based on scientific knowledge about the safety of oleic acid, a common fatty acid in foods.

The Food and Agriculture Organization (FAO) and World Health Organization (WHO) of the United Nations in 2000 said the substantial equivalence approach “is considered the most appropriate strategy for the safety and nutritional assessment of genetically modified foods.” And while substantial equivalence is not a safety assessment in itself, in that it does not characterize hazard, “it is used to structure the safety assessment of a genetically modified food relative to a conventional counterpart.”

Similarly, the Organization for Economic Cooperation and Development (OECD) in 2000 concluded: “Safety assessment based on substantial equivalence is the most practical approach to address the safety of food and food components derived through modern biotechnology.”

FDA’s Approach to Safety Assessment

In its 1992 policy on foods derived from new plant varieties, FDA employs the concept of substantial equivalence by focusing on the characteristics of the food product. This policy is intended to be applied regardless of whether the plant was derived through conventional breeding or rDNA biotechnology methods. FDA has identified certain characteristics of these foods that would dictate the need for further scrutiny to establish safety. These include a substance that is completely new to the food supply, an allergen expressed in an unusual or unexpected circumstance, changes in the concentrations of major dietary nutrients, and increased concentrations of antinutritional factors and toxins inherent to the food.

Among the key questions FDA poses are the following:

Does the source organism have a history of safe use?

Does the source of the gene introduce any toxins or allergens, which would need to be assessed in the modified plant?

For example, if a gene were obtained from a source that produced a known allergen, the proteins encoded by the introduced DNA would have to be assessed to demonstrate that this DNA did not encode an allergen for the host organism.

Safety of Introduced Genetic Material. The initial step in a safety assessment is full characterization of the genetic construct being inserted. This step includes identifying the source of the genetic material to establish that it does not originate from a pathogenic, toxin-producing, or allergenic source. Parameters measured include the size of the genetic construct that is inserted into the plant genome, the number of constructs inserted, the location of insertion, and the identification of genetic sequences within the construct that allow for its detection and expression in the plant.

The genetic material transferred is composed of DNA. All food, rDNA biotechnology-derived or otherwise, contains DNA. Since DNA occurs in all foods, it is not subject to a safety evaluation. It is well established that DNA is rapidly digested in the gastrointestinal tract and there is no evidence of DNA transfer from foods to human intestinal cells or gut microorganisms.

Earlier rDNA biotechnology-derived foods were based on the use of selectable marker genes that confer resistance to an antibiotic. Concerns were raised about the potential that the antibiotic resistance trait would be transferred to microorganisms, thereby reducing the efficacy of the antibiotic. The FAO and WHO reported in 2000 that there is no evidence that the markers currently in use pose a health risk to humans or domestic animals. Still, genes that confer resistance to drugs with specific medical use or limited alternative therapies should not be used in widely disseminated rDNA biotechnology-derived foods. The antibiotic resistance marker gene used to confer resistance to kanamycin does not present a food, feed, or environmental safety concern and is not considered toxic or allergenic. The protein gene product has been shown to be rapidly degraded, like other dietary proteins, when subjected to conditions which simulate mammalian digestion. Nonantibiotic resistance markers have mainly replaced kanamycin resistance markers in rDNA biotechnology-derived products now being developed.

Safety of the Gene Product. Once the genetic construct has been fully characterized, the FDA assesses the safety of the gene product. The gene product is the protein, often an enzyme, that is produced by the newly introduced gene or genes and is present in the rDNA biotechnologyderived food or food ingredient. An example is the protein expressed in Bt corn, encoded by genes from Bacillus thuringiensis (Bt) that confer resistance to certain insects. Safety evaluations typically include the following steps: 1) identifying the composition and structure of the gene product; 2) quantifying the amount of gene product expressed in the edible portion of the food; 3) searching for similarity to known toxins and antinutritional factors, allergens, and other functional proteins; 4) determining the thermal and digestive stability of the gene product; and 5) conducting in-vivo and in-vitro toxicological assays to demonstrate lack of apparent allergenicity or toxicity.

Unintended Effects

The FDA policy assumes a degree of knowledge and understanding about the effects of the genes being transferred. There is always the possibility that unexpected effects of gene transfer may occur, but these would be expected to occur less frequently with the use of the more precise and predictable molecular techniques than through conventional breeding. These effects have been observed only infrequently in the many thousands of crosses involving conventional crop breeding. In such cases, the source of the toxic constituent can typically be traced back to a related species used in conventional cross-breeding manipulations. For example, unusually high levels of toxic glycoalkaloids were found in the conventionally bred Lenape potato, and the U.S. Department of Agriculture subsequently withdrew the variety.


Virtually all food allergens are proteins, although only a small fraction of the proteins found in nature (and in foods) are allergenic. Since genetic modifications involve the introduction of new genes into the recipient plant and since these genes would produce new proteins in the improved variety, the potential allergenicity of the newly introduced protein is a key component of the safety assessment process.

Assessment of the potential allergenicity of rDNA biotechnology- derived foods follows the decision-tree process defined by the International Food Biotechnology Council (IFBC) and the Allergy and Immunology Institute of the International Life Sciences Institute (ILSI). This strategy focuses on several specific scientific criteria, some of which include the source of the gene(s), a comparison of the protein’s amino acid sequence to that of known allergens, and other characteristics, such as digestive stability, of the introduced protein. Based on these assessments, it should be possible to determine whether the modified food is rendered newly, or more, or less, allergenic.

The approaches to allergenicity assessment vary according to the nature of the source of the transferred genetic material. If the genetic material is obtained from a known allergenic source, either commonly or less commonly allergenic, and the encoded protein is expressed in the edible portion of the genetically modified organism, then the protein must be considered to be an allergen unless proven otherwise. In such situations, additional tests are conducted to determine the allergenicity, if any, of the introduced protein. The most difficult assessment occurs when genes are obtained from sources with no history of allergenicity, such as viruses, bacteria, or non-food plants. The likelihood that the proteins derived from such sources of DNA will be allergenic is not very high, since most proteins in nature are not allergens. In these cases, additional criteria and additional tests to use in the assessment of the allergenicity of rDNA biotechnology-derived foods would be advantageous.

The existing decision-tree approach has already been applied in the assessment of the allergenicity of rDNA biotechnology-derived foods. The enzyme introduced into glyphosate-tolerant soybeans has no sequence homology to known allergens and is rapidly digested in simulated mammalian digestion systems. Similarly, several of the Bt proteins used in insect-resistant crops and the proteins produced by common marker genes are rapidly digested in simulated mammalian digestion systems. A high-methionine protein introduced into soybeans by the introduction of a gene from Brazil nuts to correct the inherent methionine deficiency in soybeans proved allergenic to individuals. This protein was identified as the major allergen from Brazil nuts—an allergen that had not previously been characterized. As a result, commercial development in this particular soybean variety was discontinued.

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Products Without Conventional Counterparts

Recombinant DNA biotechnology-derived foods without conventional counterparts need to be evaluated on a caseby- case basis and would be subject to some types of toxicity assessments, depending on the nature of the modification. This situation has not yet arisen with rDNA biotechnologyderived foods, although at some point it undoubtedly will. When it does, the situation will raise a variety of issues that will need to be addressed in a scientifically based, flexible manner. Foremost among these issues are the limitations of long-term animal feeding studies to assess the safety of whole foods. Whole foods are complex mixtures of chemical components characterized by wide variations in composition and nutritional qualities, and are not well suited for traditional toxicological studies designed to assess individual chemical entities. Most foods will produce adverse effects in long-term animal feeding studies when fed in high proportions of the diet, regardless of the way the food was produced. The results of such studies are not easily interpreted, and apparent adverse effects are often the indirect effects of related nutritional dietary imbalance, rather than any specific compound in question.

Thus, given a hypothetical rDNA biotechnology-derived food without a conventionally derived counterpart, animal studies would need to be designed to address specific nutritional or toxicological concerns. By focusing toxicological examination on carefully selected fractions or components of a food derived from a new plant variety, and excluding major components of no concern, it may be possible to reduce or eliminate the difficulties associated with testing whole foods.

Scientific Consensus about Safety

The safety of rDNA biotechnology-derived foods has been extensively reviewed by a number of scientific organizations, at the national and international level. These organizations recognize that the use of rDNA biotechnology in itself has no impact on the safety of such foods. Foods derived using rDNA biotechnology are subject to rigorous and systematic scientific evaluations under existing principles of food safety—far more than are routinely applied to the products of traditional breeding. Thus, the level of field testing and pre-market review for food safety provides assurance that foods derived from plants and microorganisms through rDNA biotechnology are at least as safe as existing foods, and are consistent with all existing standards of food safety.

In 1987, the National Academy of Sciences (NAS) published a white paper on the planned introduction into the environment of organisms derived using rDNA biotechnology. This white paper has had wide-ranging impacts in the United States and in other countries. It stated:

“There is no evidence of the existence of unique hazards either in the use of rDNA techniques or in the movement of genes between unrelated organisms; and

“The risks associated with the introduction of rDNAengineered organisms are the same in kind as those associated with the introduction of unmodified organisms and organisms modified by other methods.”

In a 1989 extension of this white paper, the National Research Council (NRC), the research arm of the NAS, concluded that “no conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes.” The NRC further stated:

“The product of genetic modification and selection should be the primary focus for making decisions about the environmental introduction of a plant or microorganism and not the process by which the products were obtained.”

The same principles were emphasized in the 1992 comprehensive report by the United States National Biotechnology Policy Board, which was established by the Congress and composed of representatives from the public and private sectors. The report concluded that:

“Biotechnology processes tend to reduce risks because they are more precise and predictable. The health and environmental risks of not pursuing biotechnology-based solutions to the nation’s problems are likely to be greater than the risks of going forward.”

These findings are consistent with the observations and recommendations of the United Kingdom’s House of Lords Select Committee on Science and Technology, which was very critical of that nation’s policy of subjecting rDNA biotechnology-derived products to additional regulatory requirements:

“GMO-derived products should be regulated according to the same criteria as any other product.... U.K. regulation of the new biotechnology of genetic modification is excessively precautionary, obsolescent, and unscientific. The resulting bureaucracy, cost, and delay impose an unnecessary burden to academic researchers and industry alike.”

Three joint FAO/WHO consultations and the OECD, addressing specifically the question of the safety of rDNA biotechnology-derived foods, came to similar conclusions. In 1991, a joint FAO/WHO expert consultation concluded:

“Biotechnology has a long history of use in food production and processing. It represents a continuum embracing both traditional breeding techniques and the latest techniques based on molecular biology. The newer biotechnological techniques, in particular, open up very great possibilities of rapidly improving the quantity and quality of food available. The use of these techniques does not result in food which is inherently less safe than that produced by conventional ones.”

The second consultation in 1996 reaffirmed the conclusions and recommendations of the first FAO/WHO consultation: “Food safety considerations regarding organisms produced by techniques that change the heritable traits of an organism, such as rDNA technology, are basically of the same nature as those that might arise from other ways of altering the genome of an organism, such as conventional breeding…. While there may be limitations to the application of the substantial equivalence approach to safety assessment, this approach provides equal or increased assurance of the safety of food products derived from genetically modified organisms as compared to foods or food components derived by conventional methods.”

The 2000 consultation examined the evidence to date and concluded: “A comparative approach focusing on the determination of similarities and differences between the genetically modified food and its conventional counterpart aids in the identification of potential safety and nutritional issues and is considered the most appropriate strategy…. The Consultation was of the view that there were presently no alternative strategies that would provide better assurance of safety for genetically modified foods than the appropriate use of the concept of substantial equivalence.”

In a 1993 report, “Concepts and Principles Underpinning Safety Evaluation of Foods Derived by Modern Biotechnology,” the OECD offered several conclusions and recommendations that are wholly consistent with the NAS, NRC, and FAO/WHO findings. Among them:

“Modern biotechnology broadens the scope of the genetic changes that can be made in food organisms and broadens the scope of possible sources of foods. This does not inherently lead to foods that are less safe than those developed by conventional techniques.

“Therefore, evaluation of foods and food components obtained from organisms developed by the application of the newer techniques does not necessitate a fundamental change in established principles, nor does it require a different standard of safety.

“For foods and food components from organisms developed by the application of modern biotechnology, the most practical approach to the determination of safety is to consider whether they are substantially equivalent to analogous conventional food product(s), if such exist.” OECD addressed the allergenicity issue in a 1998 report, stating that “while no specific methods can be used for proteins derived from sources with no history of allergy, a combination of genetic and physicochemical comparisons exist which can be used as a screen. The application of such a strategy can provide appropriate assurance that foods derived from genetically modified products can be introduced with confidence comparable to other new plant varieties.” In 2000, OECD acknowledged public concerns about safety, calling for more transparency in the safety assessment process and better communication with the public.

The NRC’s Committee on Genetically Modified Pest- Protected Plants published a report in 2000 reaffirming the principles set forth in the 1987 NAS white paper. “[W]ith careful planning and appropriate regulatory oversight, commercial cultivation of transgenic pest-protected plants is not generally expected to pose higher risks and may pose less risk than other commonly used chemical and biological pest-management techniques,” it stated.


Based on its evaluation of the available scientific evidence, IFT’s Human Food Safety Panel reached the following conclusions:

  • Biotechnology, broadly defined, has a long history of use in food production and processing. It represents a continuum that encompasses both centuries-old traditional breeding techniques and the latest techniques based on molecular modification of genetic material, which are a major step forward by virtue of their precision and reach. The newer rDNA biotechnology techniques, in particular, offer the potential to rapidly and precisely improve the quantity and quality of food available.
  • Crops modified by modern molecular and cellular methods do not pose risks any different from those modified by earlier genetic methods for similar traits. Because the molecular methods are more specific, users of these methods will be more certain about the traits they introduce into the plants.
  • The evaluation of food, food ingredients, and animal feed obtained from organisms developed with the newer rDNA biotechnology techniques of genetic manipulation does not require a fundamental change in established principles of food safety; nor does it require a different standard of safety, even though, in fact, more information and a higher standard of safety are being required.
  • The science that underlies rDNA biotechnology-derived foods does not support more stringent safety standards than those that apply to conventional foods.
  • The use of rDNA biotechnology and molecular techniques of genetic manipulation significantly broadens the scope of the genetic changes that can be made in food organisms and broadens the scope of possible sources of foods, but this does not inherently lead to foods that are less safe than those developed by conventional techniques. By virtue of their greater precision, such products can be expected to be better characterized, leading to more predictability and a more reliable safety assessment process.

In an effort to contribute to a meaningful dialogue on scientific issues and consumer concerns about rDNA biotechnology, the Institute of Food Technologists, a non-profit society for food science and technology, conducted a comprehensive review of biotechnology. IFT convened three panels of experts, consisting of IFT members and other prominent biotechnology authorities, to evaluate the scientific evidence and write a report divided into four sections: Introduction, Safety, Labeling, and Benefits and Concerns.