Concept Of Substantial Equivalence Research Articles

A review on the safety of growth factors commonly used in cultivated meat production.

Growth factors are commonly added to cell culture media in cellular agriculture to mimic the endogenous process of proliferation and differentiation of cells. Many of these growth factors are endogenous to humans and known to be present in the edible tissues and milk of food animals. However, there is little or no information on the use of growth factors intentionally added in food production before the advent of cultivated meat. Ten commonly used growth factors have been reviewed to include information on their mode of action, bioavailability, occurrence in food and food animals, endogenous levels in humans, as well as exposure and toxicological information drawn from relevant animal studies and human clinical trials with a focus on oral exposure. In addition, a comparison of homology of growth factors was done to compare the sequence homology of growth factors from humans and domestic animal species commonly consumed as food, such as bovine, porcine, and poultry. This information has been gathered as the starting point to determine the safety of use of growth factors in cultivated meat meant for human consumption. The change in levels of growth factors measured in human milk and bovine milk after pasteurization and high-temperature treatment is discussed to give an indication of how commercial food processing can affect the levels of growth factors in food. The concept of substantial equivalence is also discussed together with a conservative exposure estimation. More work on how to integrate in silico assessments into the routine safety assessment of growth factors is needed.

Genetically modified food

International consensus has been reached on the principles regarding evaluation of the food safety of genetically modified plants. The concept of substantial equivalence has been developed as part of a safety evaluation framework, based on the idea that existing foods can serve as a basis for comparing the properties of genetically modified foods with the appropriate counterpart. Substantial equivalence is a starting point in the safety evaluation, rather than an endpoint of the assessment. The development and validation of new profiling methods, such as DNA microarray technology, proteomics and metabonomics for the identification and characterization of unintended effects, which may occur as a result of the genetic modification, is recommended. The assessment of the allergenicity of newly inserted proteins and of marker genes is discussed. Also, the post-marketing surveillance of the foods derived from genetically modified crops is imperative.

Safety assessment of genetically modified plants with deliberately altered composition.

The development and marketing of ‘novel’ genetically modified (GM) crops in which composition has been deliberately altered poses a challenge to the European Union (EU)'s risk assessment processes, which are based on the concept of substantial equivalence with a non-GM comparator. This article gives some examples of these novel GM crops and summarizes the conclusions of a report that was commissioned by the European Food Safety Authority on how the EU's risk assessment processes could be adapted to enable their safety to be assessed.

Sicherheitsbewertung von Lebensmitteln aus gentechnisch veränderten Pflanzen

The placing of genetically modified plants and derived food on the market falls under Regulation (EC) No. 1829/2003. According to this regulation, applicants need to perform a safety assessment according to the Guidance Document of the Scientific Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA), which is based on internationally agreed recommendations. This article gives an overview of the underlying legislation as well as the strategy and scientific criteria for the safety assessment, which should generally be based on the concept of substantial equivalence and carried out in relation to an unmodified conventional counterpart. Besides the intended genetic modification, potential unintended changes also have to be assessed with regard to potential adverse effects for the consumer. All genetically modified plants and derived food products, which have been evaluated by EFSA so far, were considered to be as safe as products derived from the respective conventional plants.

Risk Assessment of Genetically Modified Lactic Acid Bacteria Using the Concept of Substantial Equivalence

The use of food-grade microorganisms such as lactic acid bacteria (LAB) is one of the most promising methods for delivering health promoting compounds. Since it is not always possible to obtain strains that have the ability to produce specific compounds naturally or that produce them in sufficient quantities to obtain physiological responses, genetic modifications can be performed to improve their output. The objective of this study was to evaluate if previously studied genetically modified LAB (GM-LAB), with proven in vivo beneficial effects, are just as safe as the progenitor strain from which they were derived. Mice received an elevated concentration of different GM-LAB or the native parental strain from which they were derived during a prolonged period of time, and different health parameters were evaluated. Similar growth rates, hematological values, and other physiological parameters were obtained in the animals that received the GM-LAB compared to those that were fed with the native strain. These results demonstrate that the GM-LAB used in this study are just as safe as the native strains from which they were derived and thus merit further studies to include them into the food chain.

Beyond Equal: From Same But Different to the Doctrine of Substantial Equivalence

A same-but-different dichotomy has recently been encapsulated within the ill-defined concept of “substantial equivalence”. By invoking this concept the genetically modified organism (GMO) industry has escaped the rigors of safety testing that might otherwise apply. The curious concept of “substantial equivalence” grants a presumption of safety to GMO food. This presumption has yet to be earned, and has been used to constrain labelling of both GMO and non-GMO food. It is an idea that well serves corporatism. It enables the claim of difference to secure patent protection, while upholding the contrary claim of sameness to avoid labelling and safety scrutiny. It offers the best of both worlds for corporate food entrepreneurs, and delivers the worst of both worlds to consumers. The term “substantial equivalence” has established its currency within the GMO discourse. As the opportunities for patenting food technologies expand, the GMO recruitment of this concept will likely be a dress rehearsal for the developing debates on the labelling and testing of other techno-foods - including nano-foods and clone-foods.

Assessment of the safety of foods derived from genetically modified (GM) crops

This paper provides guidance on how to assess the safety of foods derived from genetically modified crops (GM crops); it summarises conclusions and recommendations of Working Group 1 of the ENTRANSFOOD project. The paper provides an approach for adapting the test strategy to the characteristics of the modified crop and the introduced trait, and assessing potential unintended effects from the genetic modification. The proposed approach to safety assessment starts with the comparison of the new GM crop with a traditional counterpart that is generally accepted as safe based on a history of human food use (the concept of substantial equivalence). This case-focused approach ensures that foods derived from GM crops that have passed this extensive test-regime are as safe and nutritious as currently consumed plant-derived foods. The approach is suitable for current and future GM crops with more complex modifications. First, the paper reviews test methods developed for the risk assessment of chemicals, including food additives and pesticides, discussing which of these methods are suitable for the assessment of recombinant proteins and whole foods. Second, the paper presents a systematic approach to combine test methods for the safety assessment of foods derived from a specific GM crop. Third, the paper provides an overview on developments in this area that may prove of use in the safety assessment of GM crops, and recommendations for research priorities. It is concluded that the combination of existing test methods provides a sound test-regime to assess the safety of GM crops. Advances in our understanding of molecular biology, biochemistry, and nutrition may in future allow further improvement of test methods that will over time render the safety assessment of foods even more effective and informative.

Safety assessment of foods produced through agricultural biotechnology.

Often the main criticism of foods derived from biotechnology is concerns about food safety. Whereas most present-day biotechnology-derived foods are approximately 99% similar to their non-biotechnology counterparts, the scientific community must ensure the safety of the novel aspects of these foods. The three phases of safety assessment are discussed and the concept of substantial equivalence is explained.

Genetically Modified (GM) Crops: Precautionary Science and Conflicts of Interests

Risk governance of GM plants and GMfood products is presently subject to heatedscientific and public controversies. Scientistsand representatives of the biotechnologyindustry have dominated debates concerningsafety issues. The public is suspicious withregard to the motives of scientists, companies,and political institutions involved. Thedilemmas posed are nested, embracing valuequestions, scientific uncertainty, andcontextual issues. The obvious lack of data andinsufficient information concerning ecologicaleffects call for application of thePrecautionary Principle (PP). There are,however, divergent opinions among scientistsabout the relevance of putative hazards,definition of potential ``adverse effects,'' andwhether actions should be taken to preventharm. The reliance on the concept ofsubstantial equivalence in safety evaluation ofGM food is equally controversial. Consequently,value assumptions embedded in a scientificframework may be a barrier for employment ofthe PP. One of our major conclusions is thatprecautionary GMP usage requires riskassessment criteria yet undeveloped, as well asbroader and more long-term conceptions of risk,uncertainty, and ignorance. Conflicts ofinterest and public participation are otherissues that need to be taken intoconsideration. GMP governance regimes that arejustifiable from a precautionary and ethicalpoint of view must transcend traditionalscientific boundaries to include alternativescientific perspectives as well as publicinvolvement.

Genetically modified foods, science, consumers and the media.

In contrast to the situation in the USA, where a wide range of genetically modified (GM) foods is available, in Europe very few GM products have been approved for marketing as foods, and there is widespread public concern about their safety and environmental impact. The marketing of a GM crop for food use in Europe falls under the EC novel foods regulations, and applications require the submission of an extensive dossier of information. The safety evaluation of GM foods presents considerable problems both in the conduct and interpretation of experimental studies, because conventional toxicity tests used in the evaluation of simple chemicals may not be appropriate for whole foods. To rationalise the safety evaluation process and to circumvent the difficulties in toxicological assessment of food materials, the concept of substantial equivalence has been developed. The concept is that if it can be demonstrated that the novel food is essentially similar to its conventional counterpart in terms of critical nutritional or anutritional components, then it is likely to be no more or less toxic than the latter. The possible introduction of unintended effects by the genetic modification process is particularly problematic for the safety evaluation process. The new genomic and post-genomic techniques are potentially valuable in the safety evaluation of GM foods, although they are as yet in their infancy.

Safety Assessment of Foods Derived from Genetically Modified Microorganisms

Microorganisms have a long history of use in food production, e.g. in the production of sausages, cheeses, etc. Roughly one quarter of all food products rely on microbiological processes, and the safe use of microorganisms for food production is essential. The transfer of novel traits to food microorganisms through recombinant gene technology will result in new potential food safety issues. This requires the elaboration of criteria for safety assessment of foods derived from genetic microorganisms. This joint FAO/WHO Expert Consultation was convened to consider criteria for the safety and risk assessment of food and food ingredients produced with the aid of, or containing, viable or non-viable genetically modified microorganisms (GMMs). The outcome is meant to contribute to safety and regulatory considerations by Member States and to support the development of international safety assessment guidelines for food produced with the aid of GMMs (GMM food) by the Codex ad hoc Intergovernmental Task Force on Foods Derived from Biotechnology. The Consultation concluded that the safety and risk assessment of GMM foods should proceed on a case-by-case basis considering both safety and nutritional aspects. The assessment should use the concept of substantial equivalence as a starting point, identifying differences and similarities between GMM foods and their conventional counterpart. While these differences guide the assessment, a number of additional issues require special consideration. Examples are the potential persistence of the GMM in the host gut and its interaction with the endogenous microflora, including the transfer of new genes to the gut microflora. Likewise the interaction of new genetic material with human cells in the gut, including the immune system, should be considered. The assessment of GMM foods take into consideration the history of safe use of microorganisms used in the construction. The genetic stability and pathogenic potential of the strains, as well as possible secondary effects of the genetic modification on metabolism, including the concentration of critical nutrients, antinutrients, etc. are important factors to consider. Antibiotic resistance marker genes should be avoided and their absence from the final GMM food ensured. In order to provide the basis for improved safety and risk assessment of GMM food, the Consultation recommends strengthening the capability to analyze the complex ecosystem in the human gastrointestinal tract, including work on colonization, persistence, gene transfer and host interactions. New technologies, such as molecular profiling, are developing rapidly with a potential to enhance the assessment of GMMs. The Consultation encourages further development and validation of such methods. Fermentation provides a simple technology used globally to produce food of high nutritional and hygienic quality; a technology, which is especially important in developing countries. The Consultation recommends capacity-building efforts to support the needs of developing countries in improving and evaluating this technology and its potential also in relation to GMM use. To enable efficient interaction and transparency in the safety and risk assessment of GMM food, FAO and WHO is urged to coordinate efforts to enhance the communication of safety and risk assessment principles of GMM food to all stakeholders including the public.

Assessment of the food safety issues related to genetically modified foods

International consensus has been reached on the principles regarding evaluation of the food safety of genetically modified plants. The concept of substantial equivalence has been developed as part of a safety evaluation framework, based on the idea that existing foods can serve as a basis for comparing the properties of genetically modified foods with the appropriate counterpart. Application of the concept is not a safety assessment per se, but helps to identify similarities and differences between the existing food and the new product, which are then subject to further toxicological investigation. Substantial equivalence is a starting point in the safety evaluation, rather than an endpoint of the assessment. Consensus on practical application of the principle should be further elaborated. Experiences with the safety testing of newly inserted proteins and of whole genetically modified foods are reviewed, and limitations of current test methodologies are discussed. The development and validation of new profiling methods such as DNA microarray technology, proteomics, and metabolomics for the identification and characterization of unintended effects, which may occur as a result of the genetic modification, is recommended. The assessment of the allergenicity of newly inserted proteins and of marker genes is discussed. An issue that will gain importance in the near future is that of post-marketing surveillance of the foods derived from genetically modified crops. It is concluded, among others that, that application of the principle of substantial equivalence has proven adequate, and that no alternative adequate safety assessment strategies are available.

Assessment of GM Crops in Commercial Agriculture

The caliber of recent discourse regarding genetically modified organisms (GMOs) has suffered from a lack of consensus on terminology, from the scarcity of evidence upon which to assess risk to health and to the environment, and from value differences between proponents and opponents of GMOs. Towards addressing these issues, we present the thesis that GM should be defined as the forcible insertion of DNA into a host genome, irrespective of the source of the DNA, and exclusive of conventional or mutation breeding. Some defenders of the commercial use of GMOs have referred to the scientific work of GMO critics as "junk science." Such a claim is false and misleading, given that many papers critical of both the utility and safety of GMOs have been published in peer reviewed journals by respected scientists. In contrast, there is a dearth of peer reviewed work to substantiate the frequently heard assertions of either safety or utility in GMOs. The polar- ity, which now characterizes much of the public discourse on GMOs, reflects not simply scientific disagreement, but also disagreement in underlying value assumptions. Value differences strongly affect the assessment of both benefit and harm from GMOs. The concept of substantial equivalence occupies a pivotal position in the GMO risk assessment process that is used in both Canada and the US. A GMO judged to be substan- tially equivalent to a conventional product - as have all submissions to date - is presumed to be safe enough for commercialization. The conclusion of safety - from both human health and environmental perspectives - should be based on scientific evidence, corroborated by actual experimentation. However, regulators infer safety largely from assumptions-based reasoning, with little or no experimental validation. The judgement of safety because of substantial equivalence is a dubious argument by analogy.

Safety evaluation of genetically modified foods.

The concept of substantial equivalence has been accepted as the cornerstone of the health hazard assessment of genetically modified (GM) foods (OECD 1993). Substantial equivalence is the most practical approach to address the safety of foods or food components derived from GM crops and is based on comparison of the phenotypic and compositional characteristics of the parent crop and the GM crop. Basically, three categories of GM crops can be considered (FAO/WHO 1996; EU 1997): (a) GM crops which have the same composition as the parent crop, (b) GM crops which have the same composition as the parent crop with the exception of a well-defined trait, and (c) GM crops which are different from the parent crop. For the safety assessment of the first category of GM foods only a molecular characterisation of the genetic insert is sufficient, whereas for the second category a safety assessment of the expressed protein(s) is also required. For the last category an extensive evaluation including bioavailability and wholesomeness studies are required, beside the molecular characterisation and safety assessment of the expressed protein(s) and their products. By molecular characterisation is meant the position, nature, stability and number of copies of the inserted DNA. Substantial equivalence is established by the determination of the phenotypic characteristics (e.g. resistance against diseases, agronomic properties) and the complete chemical composition of the plant including nutrients, toxicants, antinutrients, and allergens. The toxicity of the expressed protein(s) is assessed by their homology with known protein toxins, degradation in the gastro-intestinal tract, stability to food processing and acute toxicity in rodents. The possible allergenicity of the expressed proteins is evaluated by comparison of their amino acid sequence with that of known allergens and determination of their stability to digestion and food processing. If the source of the genetic insert is allergenic then the use of solid-state immunoassays, skin prick tests and even food challenge tests can be considered.

Beyond Substantial Equivalence: Ethical Equivalence

The concept of substantial equivalence,introduced for the risk assessment of geneticallymodified (GM) food, is a reducing concept because itignores the context in which these products have beenproduced and brought to the consumer at the end of thefood chain. Food quality cannot be restricted to meresubstance and food acts on human beings not only atthe level of nutrition but also through theirrelationship to environment and society. To make thiscontext explicit, I will introduce an ``equivalencescale'' for the evaluation of food chains (GM or notGM). By contrast with substantial equivalence, whichinvolves mainly quantitative, analytical methods ofevaluation, ``qualitative equivalence'' refers to ``less''or non-substantial factors that require new methodsof evaluation based on qualitative principles.``Ethical equivalence'' refers to factors that show themoral value contained in food products. To analyze thedifferent levels at which ethics is needed in foodchains, I will use the French principles: ``Liberty,Equality, Fraternity,'' or freedom, equality,solidarity, and add a fourth principle:sustainability. Sustainability, solidarity, andfreedom can be applied to the evaluation ofenvironmental, socio-economic, and socio-culturalethical equivalence, respectively. Equality refers tojustice and should operate so as to guarantee thatsustainability, solidarity, and freedom are satisfied.I suggest that ethics can provide a basis for arenewal of the food chain concept. Besides QualityAssurance, it is now essential to develop an ``EthicalAssurance'' and this equivalence scale could provide abasis to set up ``Ethical Assurance Standards'' (EAS)for food chains.

Safety Assessment of Genetically Modified Food Products: An Evaluation of Developed Approaches and Methodologies

Genetic modifications of food products are gaining more and more interest, since they represent an effective and promising way to improve a wide range of food characteristics, including production, nutritive value, and shelf life. On the other hand, concern has been raised about the safety aspects of food derived through genetically modified products. Since 1990 continuously evolving guidelines and recommendations aimed at assessing food safety have basically relied on the concept of substantial equivalence. This principle represents a dynamic approach to safety assessment and is strictly linked to other relevant issues, such as allergenicity of genetically modified products. An updated survey of strategies and methodologies generally adopted for the evaluation of safety aspects of genetically modified food products is presented.