Introduction and Overview

It is well-recognized that absolute safety is not an achievable goal in any human endeavor, and this reality is relevant to food and feed safety. The safe use of food or feed has typically been established either through experience, based on its common use, or in more recent times by application of generally recognized scientific assessment measures. For food and feed derived from genetically modified (GM) or biotech crops, Monsanto assesses each new product for safety according to rigorous procedures established by international expert bodies charged with assuring the safety of food and feed derived from crops modified using agricultural biotechnology. Since the 1990’s, the safety standard for novel food and feed crops and biotech crops in particular has been that they be as safe as an appropriate counterpart with a history of safe consumption.

Quoting the 2008 European Food Safety Authority (EFSA) GMO panel’s publication on the role of animal testing in GM crop safety assessment:

The safety assessment of GM plants and derived food and feed follows a comparative approach, i.e. the food and feed are compared with their non-GM counterparts in order to identify intended and unintended differences which subsequently are assessed with respect to their potential impact on the environment, safety for humans and animals, and nutritional quality (Concept of Substantial Equivalence or Comparative Safety Assessment, Concept of Familiarity; OECD, 1993¹; EC, 1997a²; WHO, 1995³; FAO/WHO, 2000⁴; Codex Alimentarius, 2003⁵; ENTRANSFOOD, 2004⁶; EFSA, 2006a⁷).

The comparative assessment process identifies similarities and differences between the newly developed food or feed crop and a conventional counterpart. The similarities noted between the new and traditional crop provides evidence that the newly developed crop is as safe as the crop with a history of safe consumption. The identified differences are subjected to further rigorous scientific assessment to clarify whether any safety issues or concerns exist.

The Center for Environmental Risk Assessment for example, lists over 100 country or EU food safety approvals for specific genetic events to date. In each case, the conclusion has been that foods and feeds derived from these biotech crops are as safe and nutritious as those derived from the traditional counterpart.

A stepwise evaluation scheme, first suggested by the International Life Sciences Institute⁸, has been used around the world to assess whether biotech crops are as safe as the conventional counterpart. This safety assessment process has been refined and endorsed by many organizations since that time, as summarized in Table 1. Importantly, there have been no substantiated incidents of food allergy or toxicity due to commercialized biotech crops during the first decade of their commercial adoption by millions of farmers in countries with more than half the world’s population.⁹

The food and feed safety assessment of biotechnology-derived crops considers: 1) the potential effects of the introduced trait (most often a protein) and 2) whether any unintended or pleiotropic changes have occurred due to the genetic modification process.

Safety of the Introduced Protein(s): Proteins are a necessary part of human and animal diets. The gastro-intestinal tract functions to digest dietary proteins into nutritional amino acids that are efficiently absorbed and used to make new proteins.^10,11 Because proteins are typically digested and not absorbed intact, the overwhelming majority of dietary proteins show no potential for toxicity,¹² and as a general class of macronutrients, are not normally associated with adverse effects. However, a few proteins are know to be toxic, such as venoms, bacterial toxins and certain other proteins, including lectins and enzyme inhibitors that are components of plants that are considered anti-nutrients. While anti-nutrients are not particularly toxic, repeated exposure to them can result in decreased utilization of dietary nutrients.

There are very few families of proteins that have the potential to induce food allergy when presented in a food matrix.¹³ Genetically modified crops present three different theoretical concerns¹⁴ related to the potential for allergenicity:

1. that a known protein allergen might be transferred to a crop plant;
2. that the level of endogenous protein allergens (e.g., soy allergens) might be increased; and
3. that a novel protein with no prior history of human consumption might be introduced into a crop plant and become an allergen.

Currently, the appropriate studies needed to assess the safety of the introduced protein(s) are well defined¹⁵ and takes the following into consideration:

1. the source organism from which they are derived,
2. their function and history of safe use,
3. a bioinformatic comparison to known allergens, toxins or other biologically active proteins known to have adverse effects to mammals (e.g., protease inhibitors, lectins),
4. their digestibility in a simulated gastrointestinal system,
5. their potential toxicity to mammals, and
6. appropriate toxicity studies (such as acute toxicity study) may be needed in some cases. A 28-day toxicity rodent study may be needed if there is insufficient history of safe use for the new protein.

Proteins introduced into commercially available biotech crops have been assessed for safety using this framework. Examples include: CP4 enolpyruvyl shikimic acid phosphate synthase (CP4 EPSPS) that provides glyphosate tolerance to Roundup Ready^® crops, phosphinothricin acetyltransferase (PAT) that provides glufosinate tolerance to Liberty Link^® crops, and several insecticidal proteins from Bacillus thuringiensis that provide protection from insect pests (e.g., Cry1Ab protection against the European corn borer or Cry3Bb1 protection against the corn rootworm complex).

Safety of the Food/Feed: The safety assessment of the whole food/feed derived from biotech crops is generally conducted by comparing the composition and nutritional value of the food/feed (e.g., grain, forage) to that derived from the conventional crop. An important resource to help assess whether biologically meaningful changes have occurred in the composition of the food/feed derived from the biotech crop is the ILSI Crop Composition database (www.cropcomposition.org). An understanding of the natural variability in nutrient composition of crops is an important consideration for human nutrition and also the development of diets that promote the healthy growth of livestock animals. The ILSI database is a high quality, comprehensive and publicly accessible source of data for assessing the compositional equivalence of new crop varieties as well as documenting the broad natural variability in the composition of crops.¹⁶ In the case of nutritionally enhanced crops, significant composition differences are intentional. Examples of nutritionally enhanced crops include Golden Rice 2 (provides provitamin A to address vitamin A deficiency in rice-consuming populations), Lysine maize (provides supplemental lysine for poultry and swine diets) and SDA soybeans (omega-3 fatty acid enriched soybean oil for heart health). The nutritional and safety implications of these differences must be assessed on a case-by-case basis. In some cases, a subchronic rat feeding study may be conducted with either the whole food or major processed fraction(s) to provide additional assurance of safety.

Examples of biotech crops that have completed the food/feed safety assessment include: insect-protected products, such as YieldGard^® Corn Borer, and YieldGard^® Rootworm, and BollGard^® cotton; and herbicide-tolerant crops, such as Roundup Ready^® soybeans (event 40-3-2) that was the most widely grown biotech crop in 2006, occupying more that 50 million hectares (>50% of global biotech area). Reviews on Roundup Ready^® soybeans have been completed by over 40 regulatory agencies. The product has been approved by regulators in 23 countries and one region (EU 25 member countries).

Key Components Of The Food/Feed Safety Assessment:

• The safety assessment of biotech crops begins with a comparative assessment of the new food or feed crop with an appropriate comparator crop that has a history of safe use.
• The safety of any novel protein(s) introduced into a crop is assessed using a tiered, weight-of-evidence approach. Where appropriate, safety assessment of newly introduced protein(s) would include bioinformatic analysis for similarity to known allergens, toxins, and other biologically active proteins, and confirmatory acute toxicology studies with the introduced protein(s).
• Compositional analysis of crops with known toxicants and anti-nutrient compounds includes analysis of those specific analytes. If warranted for improved nutrition crops, an evaluation of the targeted metabolic pathway also is conducted to identify specific metabolites for inclusion in the compositional analysis based on safety and/or nutritional considerations.
• The relevant phenotypic properties of the biotech crop are assessed and compared to the comparator conventional crop by growing both in representative production locations in the targeted geography for commercialization. Further study is warranted if significant unintended or unexplainable differences are identified.
• Whole food laboratory animal feeding studies also may be conducted to provide added safety assurance, although such whole food studies may lack the sensitivity to reveal unintended minor changes.
• Feeding studies with target livestock species are not part of the safety assessment, however they are important for assessing the nutritional equivalence of biotech crops intended to be compositionally equivalent to conventional crops. In addition, if the biotech crop provides an expected nutritional benefit, animal nutrition studies are used to assess the nutritional impact in the target and/or a relevant animal model.
• Premarket assessment regarding the impact of the introduction of an improved nutrition crop on the nutrient intake of consumers may often be appropriate (for example, when changes in agricultural practices or changes in consumer-led dietary intakes are anticipated). This premarket assessment could include studies in humans, on a case-by-case basis, to assess the nutritional effectiveness of the improved nutrition crop in those cases where alteration by conventional breeding would trigger similar studies.