Data Required for Safety Assessments of Plants With Novel Traits and/or Novel Livestock Feed Derived From Plants

Before a new agricultural or food product can be produced and marketed, it is thoroughly assessed for safety to protect humans, animals, and the environment. The Canadian Food Inspection Agency (CFIA) is responsible for the regulation of a number of agricultural products derived through biotechnology, including plants and livestock animal feeds. Environmental assessments of biotechnology-derived plants are carried out by the CFIA's Plant Biosafety Office (PBO). If the developers are also applying for approval of plants as livestock animal feeds, they must be assessed and approved by the CFIA's Feed Division. This fact sheet provides an overview of the PBO's Assessment Criteria for Determining Environmental Safety of Plants with Novel Traits and the Feeds Section's Guidelines for the Assessment of Livestock Feed from Plants with Novel Traits. Much of this information is overlapping.

A great deal of information and data is required from applicants to determine the safety of a plant with a novel trait (PNT). Applicants must include the methods used to obtain the information, along with bibliographic references. Below is an overview of the information that must be provided to the CFIA for environmental and livestock feed assessments. For the in-depth details on the assessments, please refer to the assessment criteria and guidelines.

What data does the CFIA use to conduct environmental assessments?

Personnel Involved and Status of the Plant with Novel Trait (PNT) in the Application

  • Name, address, phone and fax numbers (and the Canadian representative).
  • Is the plant material imported?
  • Was the plant material previously tested in Canada? If yes, in what years?
  • If the PNT was derived through recombinant DNA techniques, were the gene constructs previously tested in Canada? If yes, in what plant species and in what years?
  • Were other government agencies, either foreign or within Canada, notified of the development of the PNT or its importation? What was the purpose of this notification?

Description of the Plant with Novel Trait (PNT) and its modification

  • Confirmation of the plant's classification.
  • Designation given to the PNT, including all similar terms.
  • Parental information of the PNT (including any relationship to a previously assessed PNT).
  • Details of the use of the PNT (e.g., to be grown as a field crop for grain production, to be grown as field crop for grain production on lands contaminated with persistent herbicide, to reclaim lands contaminated with heavy metals).

Description of the modification

  • Novel gene products according to the novel traits.
  • Methods used to introduce the novel traits.
  • If the modification was achieved through recombinant DNA techniques:
    • supply a map of each genetic construct
    • for each genetic construct, list, identify source and describe them in detail
    • was the transformation vectorless? If yes, details are required.
  • In the submission of a PNT that is derived from a plant species that has more than two sets of chromosomes, the parental genome containing the genetic modification must be identified.
  • Number of generations removed from the original modification.
  • Once inserted into the plant, has each genetic modification and its expression been shown to be stable? Provide data demonstrating stability.

Description of the Novel Traits

  • Characterize in detail the gene products, breakdown products, by-products and the methods used to break down the products.
  • Are the gene products tissue-specific?
  • Are the genes expressed during a specific developmental stage?
  • Is gene expression induced? If yes, what are the inducing agents?
  • Describe the activity of the gene products, breakdown products and by-products in the host plant.
  • Describe any changes to existing metabolic pathways (including altered accumulation and storage patterns), including those that might not be intended.
  • The toxicity of the novel gene products, breakdown products and by-products in the environment must be established and described
    • potential toxigenicity to known or potential predators, grazers, parasites, pathogens, competitors and symbiont;
    • potential for adverse human health effects, such as exposure to toxins, irritants and antigens.

Biology and Interactions of the PNT

This information is requested to determine whether the PNT could potentially become a weed of agriculture, become invasive of natural habitats or be otherwise harmful to the environment.

Interactions of the PNT

  • Relative trait expression of the PNT (species replacement or competition studies may be appropriate when there is reason to believe that the biology of the plant has been altered in unpredictable ways).
  • Reproductive and survival biology.
  • Adaptations to stress factors (for biotic stress factors, identify those life forms with which the PNT interacts differently).
  • Biochemistry:
    • likelihood and change of level of exposure of consumers and other potential interacting ;
    • the effect on soil micro flora and fauna. (Observed changes at this level may warrant further in-depth studies)

Agricultural-Silviculture (Forestry Care and Cultivation) Practices

  • What are the proposed release sites for the PNT? (all of Canada? specific regions?)
  • Will the modification result in the PNT being grown outside of the normal geographic production area for the species?
  • Will the modification result in the PNT being grown outside of the usual habitat (e.g., cultivated agricultural lands) for the species?
  • Will the cultivation practices (land preparation, weed and pest control, harvest, and post-harvest protocols) involved in growing the PNT vary from those traditionally used? If yes:
    • describe the change in cultivation practices.
    • provide information showing the effect of these changes on sustainability, especially with respect to pesticide use, frequency of tillage, soil erosion and consequential changes in energy and soil conservation.
    • will volunteer plants of the PNT result in altered cultivation practices for succeeding crops?
  • If it is anticipated that the PNT will be cultivated only under contract/controlled conditions, describe:
    • any control and mitigation procedures.
    • post-harvest procedures, including procedures for disposal of remaining plant matter.
  • What deployment strategies are to be used? (for example, in forestry, the avoidance of monocultures).

Potential environmental effects resulting from introgression

Where there is potential for gene flow from the PNT into related species, detail the consequences of novel gene introgression into those species and resulting expression. Interactions identified for the original PNT should be considered, as appropriate, for these species.

What data does the CFIA use to conduct livestock feed assessments?

Data required for livestock feeds assessments is similar, in some ways, to what is required for environmental safety assessments. There are some unique items that are required, and some overlap with the assessments done by the PBO.

Development of the Modified Plant

  • This information will be made available by the Plant Biosafety Office for review by the Feed Section and will not need to be resubmitted.
  • Sufficient data should be submitted to characterize the modified plant and permit comparison with the conventional or unmodified counterpart. The presence and level of toxic or anti-nutritional compounds from novel plants developed from parents or vectors known to express these substances are of special concern.

Host and Donor Organisms

Relevant information on the donor and host organisms should be considered. A review of the literature for all information relevant to a feed safety assessment of the host plant and related varieties used in the development of the modified plant should be provided. This information should include a critical assessment of the ability of both donor and host organisms to produce potentially toxic compounds, available toxicology data, history of safe use of livestock feeds from the host plant and related varieties used in the development of the modified plant.

The Novel Trait(s)

  • Newly expressed material, which is either introduced or modified native material, should be characterized with the following information:
    • the gene product(s), breakdown products, byproducts and their metabolic pathways
    • a determination of the expression level of the gene in all plant parts that may be fed to livestock
    • determination if gene expression is present or inducible, with a description of the inducing agents
    • the activity of the gene product(s), breakdown products and byproducts in the host plant, and any resulting changes to existing metabolic pathways (including altered accumulation and storage patterns);
    • the likelihood of exposure to humans and livestock, including the estimated level and most likely route of exposure to the gene products, breakdown products, and byproducts; and
    • the potential for adverse health effects to humans and livestock, including exposure to toxins and anti-nutritional factors, and irritation and allergenicity to humans (in terms of occupational exposure).
  • Where the result of the modification is the production of novel material containing protein, similarity to products from traditional sources should be described, where appropriate.
  • Where biotechnology-derived modifications alter the expression of a traditional plant constituent, sufficient information on the anabolic or catabolic pathways should be provided to enable an assessment of possible secondary effects on related pathways and metabolite production.

Selectable Marker Genes

  • Any transformation markers used in the development of the variety must be identified. Where there are secondary effects on the biochemistry, physiology and secondary metabolism of the host plant, these should be characterized. Information should be provided on the consequences to the final plant.
  • Because antibiotics are routinely mixed with livestock feed, a determination of the potential for their inactivation during storage as a result of the activity of any expressed antibiotic resistance marker gene should be conducted.

Nutritional Data

  • Submissions must be accompanied by adequate data to demonstrate that there is no significant change in the nutritional composition of the livestock feed product(s), when compared to those originating from a presently accepted source.
  • If the composition of the proposed feed ingredient is judged not to be substantially equivalent to that of an approved feed ingredient, additional nutritional data will be required, on a case-by-case basis.
    • The required data will be a function of the potential dietary exposure, as well as nature and degree of difference with respect to the feed ingredient from an accepted source.
  • The following information is necessary to conduct a nutritional assessment of feeds from plants with novel traits.
    • a description of the feed ingredient(s) and detailed information on processing methods and proposed use(s).
    • compare the composition of the feed ingredient from the plant with the novel trait to that of the same feed ingredient from an unmodified host, and, if necessary, other varieties of the host type.
  • Scientific investigations presented in support of nutritional equivalence must be done.

Nutrient Composition

  • The following analyses should be conducted on all feeds from plants with novel traits:
    • crude protein
    • crude fat
    • fibre, any of crude fibre, ADF (Acid Detergent Fibre) or NDF (Neutral Detergent Fibre)
  • A statistical comparison of these nutrients should be undertaken and both the raw data and computer printouts of statistical analysis must accompany the submission.
  • Based on the preceding evaluation and the intended use of the feed, the following information may also be required :
    • content of true protein, non-protein nitrogenous material, and amino acid profile;
    • quantitative and qualitative composition of total lipids, i.e., saponifiable and non-saponifiable components, and complete fatty acid profile;
    • composition of the carbohydrate fraction, e.g., sugars, chitin, tannins, non-starch polysaccharides and lignins investigated;
    • qualitative and quantitative composition of vitamins, i.e., complete vitamin analysis;
    • mineral analysis; and
    • presence of naturally occurring or adventitious antinutritional factors which could reasonably be expected to be present, e.g. phytates, trypsin inhibitors, alkaloids, pigments, etc.

Dietary Exposure

  • Estimates of dietary exposure to the novel feed may play a key role in determining the data required for a safety and efficacy assessment.
  • In addition, data on the effects of animal age and species with respect to the intended use of the novel feed may be necessary.

Toxicology Data

  • If concerns remain after assessment of the data submitted, toxicity studies may be required.
  • The potential for allergenic response in humans (in terms of occupational safety) would be considered on the basis of the history of the host and donor organisms and the novel traits introduced.

Laboratory Animal/Livestock Feeding Trials

  • Laboratory animal studies and/or livestock feeding trials may be required to address any toxicological or nutritional concerns arising from an assessment of the data submitted.
  • Animal studies may also be needed as evidence of nutritional adequacy including nutrient bioavailability. The necessity for these studies would be determined based on an assessment of the data submitted, especially where the feed is a significant source of dietary nutrients.

Environmental Safety

  • An evaluation of the release of imported feed derived from plants with novel traits into the environment, or byproducts thereof, will be required if an assessment has not already been undertaken by the CFIA's Plant Biosafety Office.