In food safety, the concept of substantial equivalence holds that the safety of a new food, particularly one that has been genetically modified (GM), may be assessed by comparing it with a similar traditional food that has proven safe in normal use over time. [1] It was first formulated as a food safety policy in 1993, by the Organisation for Economic Co-operation and Development (OECD). [2]
As part of a food safety testing process, substantial equivalence is the initial step, establishing toxicological and nutritional differences in the new food compared to a conventional counterpart—differences are analyzed and evaluated, and further testing may be conducted, leading to a final safety assessment. [3]
Substantial equivalence is the underlying principle in GM food safety assessment for a number of national and international agencies, including the Canadian Food Inspection Agency (CFIA), Japan's Ministry of Health, Labour and Welfare (MHLW), the US Food and Drug Administration (FDA), and the United Nations' Food and Agriculture Organization (FAO) and World Health Organization. [4]
The concept of comparing genetically modified foods to traditional foods as a basis for safety assessment was first introduced as a recommendation during the 1990 Joint FAO/WHO Expert Consultation on biotechnology and food safety (a scientific conference of officials and industry), although the term substantial equivalence was not used. [5] [6] Adopting the term, substantial equivalence was formulated as a food safety policy by the OECD, first described in their 1993 report, "Safety Evaluation of Foods Derived by Modern Biotechnology: Concepts and Principles. [2]
The term was borrowed from the FDA's 1976 substantial equivalence definition for new medical devices—under Premarket Notification 510(k), a new Class II device that is essentially similar to an existing device can be cleared for release without further testing. [2] [7] The underlying approach of comparing a new product or technique to an existing one has long been used in various fields of science and technology. [2]
The concept was reinforced by a joint FAO/WHO expert consultation in 1996. This meeting emphasized that substantial equivalence does not in itself constitute a safety assessment, but provides a framework for organizing the analysis of foods derived from plants with recombinant DNA, considering their characteristics and composition. When a new product is considered equivalent to a conventional food with a history of safe consumption, it is understood that it will be as safe as the traditional food, provided it is used under similar consumption and processing standards. The FAO emphasizes that one of the main advantages of the concept is its flexibility, which is useful in assessing the safety of foods derived from modern biotechnology. It allows for the identification of differences that may require further investigation. Because it is based on a comparison, it can be applied at different stages of the food chain, such as in the harvested product, in processed fractions, or in the final food, directing the analysis to the most appropriate level according to the nature of the product. [8]
In June 1999, G8 leaders requested the OECD to “undertake a study on the implications of biotechnology and other aspects of food safety.” In 2000, the OECD Edinburgh Conference on Scientific and Health Aspects of Genetically Modified Foods was held. Following those discussions, the OECD published an opinion that substantial equivalence is an important tool in analyzing the safety of novel foods, including GM foods. The document noted that substantial equivalence serves as a framework for approaching food safety assessment, rather than functioning as a quantitative standard or measure. [9]
In 2000, a new joint FAO/WHO consultation on foods derived from biotechnology revisited the concept. The group concluded that safety assessment should follow an integrated, step-by-step, case-by-case approach, supported by a structured set of questions. It was reaffirmed that substantial equivalence, when comparing foods derived from genetically modified plants with their conventional counterparts, is the most appropriate strategy for identifying potential safety and nutrition issues. It was also emphasized that substantial equivalence does not replace risk analysis—since it does not directly characterize hazards—but should guide the comparative process in relation to the conventional food used as a reference. The experts considered the methodology used in the safety assessment of genetically modified foods approved commercially to date to be satisfactory and concluded that the application of substantial equivalence strengthens the existing assessment framework. According to the consultation, there were no alternative strategies at the time that offered greater safety guarantees. [8]
The OECD bases the substantial equivalence principle on a definition of food safety where we can assume that a food is safe for consumption if it has been eaten over time without evident harm. It recognizes that traditional foods may naturally contain toxic components (usually called antinutrients)—such as the glycoalkaloids solanine in potatoes and alpha-tomatine in tomatoes—which do not affect their safety when prepared and eaten in traditional ways. [10] [11] [8] [note 1]
The report proposes that, while biotechnology broadens the scope of food modification, it does not inherently introduce additional risk, and therefore, GM products may be assessed in the same way as conventionally bred products. [1] Further, the relative precision of biotech methods should allow assessment to be focused on the most likely problem areas. [1] The concept of substantial equivalence is then described as a comparison between a GM food and a similar conventional food, taking into account food processing, and how the food is normally consumed, including quantity, dietary patterns, and the characteristics of the consuming population. [note 2]
Substantial equivalence is the starting point for GM food safety assessment: significant differences between a new food item and its conventional counterpart would indicate the need for further testing. A "targeted approach" is taken, by selecting specific relevant molecules for comparison. For plants, selection of a suitable comparator may involve growing the new plant side by side with genetically closely related varieties, or using publicly available composition data for closely related varieties. [9]
Evaluation for substantial equivalence can be applied at different points in the food chain, from unprocessed harvested crop to final ingredient or product, depending on the nature of the food item and its intended use. [8]
For a GM plant, the overall evaluation process may be viewed in four phases: [3]
There is a scientific consensus [12] [13] [14] [15] [16] that currently available food derived from GM crops poses no greater risk to human health than conventional food, [17] [18] [19] [20] [21] [22] [23] but that each GM food needs to be tested on a case-by-case basis before introduction. [24] [25] [26] Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe. [27] [28] [29] [30] The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation, [31] [32] [33] [34] which varied due to geographical, religious, social, and other factors. [35] [36] [37] [38] [39]
There has been discussion about applying new biochemical concepts and methods in evaluating substantial equivalence, such as metabolic profiling and protein profiling. These concepts refer, respectively, to the complete measured biochemical spectrum (total fingerprint) of compounds (metabolites) or of proteins present in a food or crop. The goal would be to compare overall the biochemical profile of a new food to an existing food to see if the new food's profile falls within the range of natural variation already exhibited by the profile of existing foods or crops. However, these techniques are not considered sufficiently evaluated, and standards have not yet been developed, to apply them. [40] [ better source needed ]
Approaches to GM food regulation vary by country, while substantial equivalence is generally the underlying principle of GM food safety assessment. This is the case for national and international agencies that include the Canadian Food Inspection Agency (CFIA), Japan's Ministry of Health, Labour and Welfare (MHLW), the US Food and Drug Administration (FDA), and the United Nations' Food and Agriculture Organization (FAO) and World Health Organization. [8] [41] [4] In 1997, the European Union established a novel food assessment procedure whereby, once the producer has confirmed substantial equivalence with an existing food, government notification, with accompanying scientific evidence, is the only requirement for commercial release, however, foods containing genetically modified organisms (GMOs) are excluded and require mandatory authorization. [2]
To establish substantial equivalence, the modified product is tested by the manufacturer for unexpected changes to a targeted set of components such as toxins, nutrients, or allergens, that are present in a similar unmodified food. The manufacturer's data is then assessed by a regulatory agency. If regulators determine that there is no significant difference between the modified and unmodified products, then there will generally be no further requirement for food safety testing. However, if the product has no natural equivalent, or shows significant differences from the unmodified food, or for other reasons that regulators may have (for instance, if a gene produces a protein that has not been a food component before), further safety testing may be required. [1]
We have reviewed the scientific literature on GE crop safety for the last 10 years that catches the scientific consensus matured since GE plants became widely cultivated worldwide, and we can conclude that the scientific research conducted so far has not detected any significant hazard directly connected with the use of GM crops.
The literature about Biodiversity and the GE food/feed consumption has sometimes resulted in animated debate regarding the suitability of the experimental designs, the choice of the statistical methods or the public accessibility of data. Such debate, even if positive and part of the natural process of review by the scientific community, has frequently been distorted by the media and often used politically and inappropriately in anti-GE crops campaigns.
Currently available transgenic crops and foods derived from them have been judged safe to eat and the methods used to test their safety have been deemed appropriate. These conclusions represent the consensus of the scientific evidence surveyed by the ICSU (2003) and they are consistent with the views of the World Health Organization (WHO, 2002). These foods have been assessed for increased risks to human health by several national regulatory authorities (inter alia, Argentina, Brazil, Canada, China, the United Kingdom and the United States) using their national food safety procedures (ICSU). To date no verifiable untoward toxic or nutritionally deleterious effects resulting from the consumption of foods derived from genetically modified crops have been discovered anywhere in the world (GM Science Review Panel). Many millions of people have consumed foods derived from GM plants - mainly maize, soybean and oilseed rape - without any observed adverse effects (ICSU).
There is broad scientific consensus that genetically engineered crops currently on the market are safe to eat. After 14 years of cultivation and a cumulative total of 2 billion acres planted, no adverse health or environmental effects have resulted from commercialization of genetically engineered crops (Board on Agriculture and Natural Resources, Committee on Environmental Impacts Associated with Commercialization of Transgenic Plants, National Research Council and Division on Earth and Life Studies 2002). Both the U.S. National Research Council and the Joint Research Centre (the European Union's scientific and technical research laboratory and an integral part of the European Commission) have concluded that there is a comprehensive body of knowledge that adequately addresses the food safety issue of genetically engineered crops (Committee on Identifying and Assessing Unintended Effects of Genetically Engineered Foods on Human Health and National Research Council 2004; European Commission Joint Research Centre 2008). These and other recent reports conclude that the processes of genetic engineering and conventional breeding are no different in terms of unintended consequences to human health and the environment (European Commission Directorate-General for Research and Innovation 2010).
But see also:
Domingo, José L.; Bordonaba, Jordi Giné (2011). "A literature review on the safety assessment of genetically modified plants" (PDF). Environment International. 37 (4): 734–742. Bibcode:2011EnInt..37..734D. doi:10.1016/j.envint.2011.01.003. PMID 21296423. In spite of this, the number of studies specifically focused on safety assessment of GM plants is still limited. However, it is important to remark that for the first time, a certain equilibrium in the number of research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was observed. Moreover, it is worth mentioning that most of the studies demonstrating that GM foods are as nutritional and safe as those obtained by conventional breeding, have been performed by biotechnology companies or associates, which are also responsible of commercializing these GM plants. Anyhow, this represents a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies.
Krimsky, Sheldon (2015). "An Illusory Consensus behind GMO Health Assessment". Science, Technology, & Human Values. 40 (6): 883–914. doi:10.1177/0162243915598381. S2CID 40855100. I began this article with the testimonials from respected scientists that there is literally no scientific controversy over the health effects of GMOs. My investigation into the scientific literature tells another story.
And contrast:
Panchin, Alexander Y.; Tuzhikov, Alexander I. (January 14, 2016). "Published GMO studies find no evidence of harm when corrected for multiple comparisons". Critical Reviews in Biotechnology. 37 (2): 213–217. doi:10.3109/07388551.2015.1130684. ISSN 0738-8551. PMID 26767435. S2CID 11786594. Here, we show that a number of articles some of which have strongly and negatively influenced the public opinion on GM crops and even provoked political actions, such as GMO embargo, share common flaws in the statistical evaluation of the data. Having accounted for these flaws, we conclude that the data presented in these articles does not provide any substantial evidence of GMO harm.
The presented articles suggesting possible harm of GMOs received high public attention. However, despite their claims, they actually weaken the evidence for the harm and lack of substantial equivalency of studied GMOs. We emphasize that with over 1783 published articles on GMOs over the last 10 years it is expected that some of them should have reported undesired differences between GMOs and conventional crops even if no such differences exist in reality.
and
Yang, Y.T.; Chen, B. (2016). "Governing GMOs in the USA: science, law and public health". Journal of the Science of Food and Agriculture. 96 (4): 1851–1855. Bibcode:2016JSFA...96.1851Y. doi:10.1002/jsfa.7523. PMID 26536836.It is therefore not surprising that efforts to require labeling and to ban GMOs have been a growing political issue in the USA (citing Domingo and Bordonaba, 2011). Overall, a broad scientific consensus holds that currently marketed GM food poses no greater risk than conventional food... Major national and international science and medical associations have stated that no adverse human health effects related to GMO food have been reported or substantiated in peer-reviewed literature to date.
Despite various concerns, today, the American Association for the Advancement of Science, the World Health Organization, and many independent international science organizations agree that GMOs are just as safe as other foods. Compared with conventional breeding techniques, genetic engineering is far more precise and, in most cases, less likely to create an unexpected outcome.
The EU, for example, has invested more than €300 million in research on the biosafety of GMOs. Its recent report states: "The main conclusion to be drawn from the efforts of more than 130 research projects, covering a period of more than 25 years of research and involving more than 500 independent research groups, is that biotechnology, and in particular GMOs, are not per se more risky than e.g. conventional plant breeding technologies." The World Health Organization, the American Medical Association, the U.S. National Academy of Sciences, the British Royal Society, and every other respected organization that has examined the evidence has come to the same conclusion: consuming foods containing ingredients derived from GM crops is no riskier than consuming the same foods containing ingredients from crop plants modified by conventional plant improvement techniques.
A report issued by the scientific council of the American Medical Association (AMA) says that no long-term health effects have been detected from the use of transgenic crops and genetically modified foods, and that these foods are substantially equivalent to their conventional counterparts." "Crops and foods produced using recombinant DNA techniques have been available for fewer than 10 years and no long-term effects have been detected to date. These foods are substantially equivalent to their conventional counterparts.
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.
Several scientific organizations in the US have issued studies or statements regarding the safety of GMOs indicating that there is no evidence that GMOs present unique safety risks compared to conventionally bred products. These include the National Research Council, the American Association for the Advancement of Science, and the American Medical Association. Groups in the US opposed to GMOs include some environmental organizations, organic farming organizations, and consumer organizations. A substantial number of legal academics have criticized the US's approach to regulating GMOs.
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 commercialized GE with 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.
Different GM organisms include different genes inserted in different ways. This means that individual GM foods and their safety should be assessed on a case-by-case basis and that it is not possible to make general statements on the safety of all GM foods.
GM foods currently available on the international market have passed safety assessments and are not likely to present risks for human health. In addition, no effects on human health have been shown as a result of the consumption of such foods by the general population in the countries where they have been approved. Continuous application of safety assessments based on the Codex Alimentarius principles and, where appropriate, adequate post market monitoring, should form the basis for ensuring the safety of GM foods.
These principles dictate a case-by-case premarket assessment that includes an evaluation of both direct and unintended effects.
In our view, the potential for GM foods to cause harmful health effects is very small and many of the concerns expressed apply with equal vigour to conventionally derived foods. However, safety concerns cannot, as yet, be dismissed completely on the basis of information currently available.
When seeking to optimise the balance between benefits and risks, it is prudent to err on the side of caution and, above all, learn from accumulating knowledge and experience. Any new technology such as genetic modification must be examined for possible benefits and risks to human health and the environment. As with all novel foods, safety assessments in relation to GM foods must be made on a case-by-case basis.
Members of the GM jury project were briefed on various aspects of genetic modification by a diverse group of acknowledged experts in the relevant subjects. The GM jury reached the conclusion that the sale of GM foods currently available should be halted and the moratorium on commercial growth of GM crops should be continued. These conclusions were based on the precautionary principle and lack of evidence of any benefit. The Jury expressed concern over the impact of GM crops on farming, the environment, food safety and other potential health effects.
The Royal Society review (2002) concluded that the risks to human health associated with the use of specific viral DNA sequences in GM plants are negligible, and while calling for caution in the introduction of potential allergens into food crops, stressed the absence of evidence that commercially available GM foods cause clinical allergic manifestations. The BMA shares the view that there is no robust evidence to prove that GM foods are unsafe but we endorse the call for further research and surveillance to provide convincing evidence of safety and benefit.
The largest differences between the public and the AAAS scientists are found in beliefs about the safety of eating genetically modified (GM) foods. Nearly nine-in-ten (88%) scientists say it is generally safe to eat GM foods compared with 37% of the general public, a difference of 51 percentage points.