Genetically Modified Organisms (GMO)


Fate and Transport in the Environment

Exposure Pathway

Routes of Exposure

Methods for Measuring Exposure

Strategies for Preventing Exposure

Methods for Monitoring in the Environment

Harmful Effects

Dose Response

Absorption, Distribution and Metabolism

Sites of Toxicity

Biomarkers of Disease

Risk Assessment


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Risk Assessment

Risk is defined as the likelihood that adverse effects will result from exposure to a substance (Timbrell, 2003). Traditional risk assessment involves identifying a hazardous substance, demonstrating a dose-response relationship, assessing the likelihood of exposure to humans, and estimating the incidence of adverse effects under the various conditions of human exposure. For food additives risk assessment usually involves the determination of an Acceptable Daily Intake or Reference Dose.

While consideration of genetically modified foods incorporates some aspects of traditional risk assessment, these products are intended for repeated, chronic human exposure so no detectable risk is acceptable. GM food developers therefore focus mainly on safety assessment or the certainty that no adverse effects will occur when the product is used as intended (Cockburn, 2002; Trimbrell, 2003).

The paradigm that was developed to assess the safety of genetically modified foods is known as “substantial equivalence” and was jointly developed in 1991 by the Food and Agriculture Organization and the World Health Organization in order to provide a standardized international methodology for the safety assessment of GM foods. Government regulations in the U.S., E.U., Canada, Japan, and most other countries are based upon the concept of substantial equivalence (Cockburn, 2002).

Substantial equivalence is based on the determination of any differences between a GM food and its traditional counterpart, which has traditionally been regarded as safe. Equivalence is divided into four categories (Cockburn, 2002).

  1. Phenotypic and agronomic equivalence focuses on the morphology and agronomic traits of the GM product as compared to its non-GM counterpart.
  2. Compositional equivalence tests whether the GM product has the same composition of macro and micronutrients as the non-GM counterpart.
  3. Safety equivalence focuses on the hazard assessment of the introduced gene and its expressed protein.
  4. Nutritional and feed performance equivalence focuses on whether the GM product yields the same feed efficiency in animals as its non-GM component.

The safety equivalence category involves traditional toxicological and risk assessment methods more than the others. When considering safety equivalence, safety assessors focus on the source of potential hazard in genetically modified foods. The source of the hazard can be divided into four categories (Cockburn, 2002).

  1. The traditional host crop
  2. The gene donor
  3. The gene product
  4. The transformed crop

Direct toxicological assessment focuses on the gene product and the transformed crop. This generally involves acute toxicity testing in animals to assess the effects of a single high dose of the protein. If the protein is used as a pesticide it is usually tested at a limit dose set by the EPA other wise the protein is usually tested at a dose that corresponds to at least 100 times the expected oral exposure of humans. If the acute toxicity study yields adverse effects, then repeat dose toxicity studies are applied. The specific type of test used depends on the nature of the protein being considered (Cockburn, 2002).

Along with direct toxicity testing, the potential allergenicity of the gene product needs to be assessed. This can be difficult because there are no reliable models to predict human food allergy unless the gene product comes from a known allergenic source. If that is the case, the protein can be tested in vitro using serum from individuals known to be allergic to the gene donor. This procedure was used to determine that a variety of soybean containing a gene from Brazil nuts could cause allergic reactions in people (Cockburn, 2002; Bakshi, 2003).

Usually the gene product comes from a source of unknown allergenic status. In this case an indirect approach is used to evaluate the protein’s potential allergenicity using a decision tree that was developed by the OECD, WHO, and IFBC. The decision tree involves looking for qualities in the gene product that are characteristic of known allergens such as large size, certain amino acid sequences, or resistance to degradation in stomach acid (Cockburn, 2002). A variety of GM corn was approved for non-human consumption only because the introduced protein showed resistance to degradation (Cockburn, 2002).

If the safety testing of the introduced gene and its product produce no adverse effects and the GM product is shown to be substantially equivalent to its non-GM counterpart in all other ways, the new product is approved for the market and is not regulated by the government.