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October 13 - 15, 2004 Meeting Agenda

DRAFT

September 15, 2004

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
OPEN MEETING
OCTOBER 13-15, 2004
FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/
OPP Docket Telephone: (703) 305-5805
Docket Number: OPP-2004-0287

ISSUES ASSOCIATED WITH DEPLOYMENT OF A TYPE OF PLANT-INCORPORATED PROTECTANT (PIP), SPECIFICALLY THOSE BASED ON PLANT VIRAL COAT PROTEINS (PVCP-PIPS)

WEDNESDAY, OCTOBER 13, 2004
Holiday Inn - National Airport
2650 Jefferson Davis Highway
Arlington,VA 22202
Telephone: (703) 684-7200

Gene Flow

Concerns about the transfer of virus resistance to wild or weedy relatives include the assumption that such resistance might confer a selective advantage to a wild or weedy relative that could increase its competitive ability and potential to become weedy or invasive. The Agency would like the panel to consider the evidence supporting this assumption.
1. What scientific evidence supports or refutes the idea that plant viruses have significant effects on reproduction, survival, and growth of plant populations in natural settings? Is there scientific evidence that plant populations freed from viral pressure could have increased competitive ability leading to changes in plant population dynamics?

2. Please comment on the validity of the Agency list of crops that have no wild or weedy relatives in the United States with which they can produce viable hybrids in nature (i.e., tomato, potato, soybean, and corn).

  • 3:00 PM BREAK
  • 3:15 PM Panel Discussion (continued)

    3. Please identify other crops that have no wild or weedy relatives in the United States with which they can produce viable hybrids in nature, e.g., papaya, peanut, and/or chickpea.
    The Agency anticipates the need to evaluate data addressing whether transgenic plant species are capable of genetic exchange with wild or weedy plant relatives. In general, EPA is focused on the potential for genetic exchange that can occur in the field. However, evaluations of the potential for genetic exchange are likely to include laboratory studies that are not necessarily an accurate indicator of plants’ ability to exchange genetic material outside the lab.
    4. What laboratory techniques used to achieve genetic exchange between species (e.g., embryo rescue, use of intermediate bridging crosses, protoplast fusion) are not indicative of possible genetic exchange between these species in the field? Conversely, what techniques, if any, used in laboratory or greenhouse experiments provide the most reliable indication of ability to hybridize in the field?

  • 4:30 PM ADJOURNMENT

    FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
    OPEN MEETING
    OCTOBER 13-15, 2004
    FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/
    OPP Docket Telephone: (703) 305-5805
    Docket Number: OPP-2004-0287

    ISSUES ASSOCIATED WITH DEPLOYMENT OF A TYPE OF PLANT-INCORPORATED PROTECTANT (PIP), SPECIFICALLY THOSE BASED ON PLANT VIRAL COAT PROTEINS (PVCP-PIPS)

    THURSDAY, OCTOBER 14, 2004
    Holiday Inn - National Airport
    2650 Jefferson Davis Highway
    Arlington,VA 22202
    Telephone: (703) 684-7200

    7. Please specify techniques that do or do not provide measures of tolerance and/or resistance that are relevant to field conditions.
    8. How do environmental or other factors (e.g., temporal variations) affect tolerance and/or resistance? Given the expected variability, what measures of tolerance and/or resistance would be reliable?
    9. What would be the ecological significance if a plant population acquired a small increase in viral tolerance and/or resistance above a naturally-occurring level?

    Based on the hypothesis that concerns about the consequences of gene flow to a wild or weedy relative in the United States may be negligible in certain cases, the Agency is considering whether there are mechanisms to adequately address concerns associated with gene flow so that certain types of VCPs would be of such low risk that they would not need to be regulated by EPA. Below are examples of three conditions (modified from those proposed in 1994) that are intended to significantly reduce any potential adverse effects of gene flow with plants containing a PVCP-PIP.

    (1) The plant into which the PVCP-PIP has been inserted has no wild or weedy relatives in the United States with which it can produce viable hybrids in nature, e.g., corn, tomato, potato, or soybean; or

    (2) Genetic exchange between the plant into which the PVCP-PIP has been inserted and any existing wild or weedy relatives is substantially reduced by modifying the plant with a scientifically documented method (e.g., through male sterility); or

    (3) It has been empirically demonstrated that all existing wild or weedy relatives in the United States with which the plant can produce a viable hybrid are tolerant or resistant to the virus from which the coat protein is derived.

    10. Please comment on how necessary and/or sufficient these conditions are to minimize the potential for the PVCP-PIP to harm the environment through gene flow from the plant containing the PVCP-PIP to wild or weedy relatives. Would any other conditions work as well or better?

  • 12:00 PM LUNCH
  • 1:00 PM Panel Discussion (continued)

    Viral Interactions
    Interactions between introduced plant virus sequences and other invading viruses in transgenic plants (e.g., during recombination or heterologous encapsidation) may be a concern to the extent that such events may increase in frequency or be unlike those expected to occur in nature. It has been hypothesized that such events could lead to the creation of viruses with new disease states or transmission properties. The Agency is evaluating the circumstances that might increase the potential for such events to occur and the potential environmental consequences of novel viral interactions in light of the 2000 NRC report which stated that, “[m]ost virus-derived resistance genes are unlikely to present unusual or unmanageable problems that differ from those associated with traditional breeding for virus resistance.” The report went on to suggest that risks might be managed by particular ways of engineering transgenes. However, under either of the 1994 proposed exemptions, the Agency would be unable to ensure that such strategies were implemented. The Agency’s literature review, “Viral interactions in viral coat protein transgenic plants,” discusses possible ways of managing these potential risks in detail.
    Viral interactions may occur in natural, mixed infections which are common in plants. Hypothetical concerns related to potential adverse effects resulting from viral interactions between infecting viruses and PVCP-PIPs in transgenic plants may be attributed to opportunities for interactions not expected to occur in nature. EPA is interested in evaluating the significance of novel viral interactions involving a viral transgene.
    11. To what extent are novel viral interactions (e.g., recombination, heterologous encapsidation) involving a viral transgene an environmental concern?
    Mixed viral infections can be extremely common in crops and other plants. However, scientific uncertainty exists as to whether recombination and heterologous encapsidation would occur more or less frequently in the case of a viral transgene and an infecting virus interaction as compared to such interactions in mixed infections of a transgenic plant’s non-bioengineered counterpart.
    12. What conclusions can be drawn as to whether the likelihood of recombination and/or heterologous encapsidation would be increased or decreased in a transgenic plant compared to its non-bioengineered counterpart?

  • 3:00 PM BREAK
  • 3:15 PM Panel Discussion (continued)

    A number of methods for reducing the frequency of recombination and heterologous encapsidation have been identified. While the effectiveness of these techniques has been verified for particular cases, their applicability to all PVCP-PIPs is unclear. Recognizing that it would be difficult for a product developer to measure rates of recombination, heterologous encapsidation, or vector transmission under field conditions, EPA is considering whether it would be necessary to verify that such methods worked in any particular instance by measuring rates in modified versus unmodified plants.
    13. How effective is deleting the 3’ untranslated region of the PVCP gene as a method for reducing the frequency of recombination in the region of the PVCP gene? Is this method universally applicable to all potential PVCP-PIP constructs? Would any other methods work as well or better? Which methods are sufficiently effective and reproducible such that actual measurement of rates to verify rate reduction would be unnecessary?
    14. Are any methods for inhibiting heterologous encapsidation or transmission by insect vectors universally applicable to all PVCP-PIPs? Which methods are sufficiently effective and reproducible such that actual measurement of rates to verify rate reduction would be unnecessary?
    15. How technically feasible would it be to measure rates of recombination, heterologous encapsidation, and vector transmission in PVCP-PIP transgenic plants in order to show that rates are reduced?

  • 5:00 PM ADJOURNMENT

    FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
    OPEN MEETING
    OCTOBER 13-15, 2004
    FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/
    OPP Docket Telephone: (703) 305-5805
    Docket Number: OPP-2004-0287

    ISSUES ASSOCIATED WITH DEPLOYMENT OF A TYPE OF PLANT-INCORPORATED PROTECTANT (PIP), SPECIFICALLY THOSE BASED ON PLANT VIRAL COAT PROTEINS (PVCP-PIPS)

    FRIDAY, OCTOBER 15, 2004
    Holiday Inn - National Airport
    2650 Jefferson Davis Highway
    Arlington,VA 22202
    Telephone: (703) 684-7200

    Other questions

    In 1994 EPA proposed exempting plant viral coat proteins from the requirement of a food tolerance under the Federal Food, Drug, and Cosmetic Act based on rationale that (1) virus infected plants have always been a part of the human and domestic animal food supply and (2) plant viruses have never been shown to be infectious to humans or mammals. The safety of consuming plant virus genes has been supported by experimental work (Chen et al. 2003; Rogan et al. 2000; Shinmoto et al. 1995) and expert consultations including the 2000 NRC report which concluded that, “viral coat proteins in transgenic pest-protected plants are not expected to jeopardize human health because consumers already ingest these compounds in nontransgenic food.” However, EPA recognizes that PVCP-PIP developers may wish to modify the PVCP-PIP construct and that some methods of mitigating potential risks associated with recombination and heterologous encapsidation might actually require them to do so. Such modifications might result in changes to the protein(s) produced thus creating potential food safety concerns, e.g., inadvertent production of new toxins or allergens (Day 1996). Modifications of the construct and alteration of the proteins produced creates the potential for health impacts on non-target species as well as humans.

    17. To what degree and in what ways might a PVCP gene be modified (e.g., through truncations, deletions, insertions, or point mutations) while still retaining scientific support for the idea that humans have consumed the products of such genes for generations and that such products therefore present no new dietary exposures?

    18. What are the potential adverse effects, if any, of such modifications on nontarget species (e.g., wildlife and insects that consume the PVCP-PIP)?

    Modifications of the construct may also potentially create the opportunity for novel viral interactions because the inserted virus sequences could be unlike any that occur naturally.

    19. To what degree and in what ways might a PVCP gene be modified (e.g., through truncations, deletions, insertions, or point mutations) before it would be a concern that novel viral interactions due to the modifications could occur because the PVCP gene would be significantly different from any existing in nature?
    The potential risk issues identified in this paper are specific to virus-resistant transgenic plants. However, the Agency recognizes that it may be necessary to evaluate other information related to the PVCP-PIP.

    20. Would any additional requirements related to PVCP-PIP identity and composition (e.g., demonstration that the transgene has been stably inserted) be needed for significant reduction of risks associated with PVCP-PIPs?

    21. Are there any considerations beyond gene flow, recombination, and heterologous encapsidation as posed in the preceding questions that the Agency should consider in evaluating the risk potential of PVCP-PIPs (e.g., synergy)?

  • 3:00 PM ADJOURNMENT

    Please be advised that agenda times are approximate. For further information, please contact the Designated Federal Official for this meeting, Mr. Paul Lewis, via telephone: (202) 564-8450; fax: (202) 564-8382; or email: lewis.paul@epa.gov


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