[Federal Register Volume 72, Number 74 (Wednesday, April 18, 2007)]
[Proposed Rules]
[Pages 19590-19640]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-7297]
[[Page 19589]]
-----------------------------------------------------------------------
Part II
Environmental Protection Agency
-----------------------------------------------------------------------
40 CFR Part 174
Exemption Under the Federal Insecticide, Fungicide, and Rodenticide
Act for Certain Plant-Incorporated Protectants Derived From Plant Viral
Coat Protein (PVCP-PIPs) Gene(s); Supplemental Proposal; Proposed Rules
Federal Register / Vol. 72, No. 74 / Wednesday, April 18, 2007 /
Proposed Rules
[[Page 19590]]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 174
[EPA-HQ-OPP-2006-0642; FRL-8100-7]
RIN 2070-AD49
Exemption Under the Federal Insecticide, Fungicide, and
Rodenticide Act for Certain Plant-Incorporated Protectants Derived From
Plant Viral Coat Protein Gene(s) (PVCP-PIPs); Supplemental Proposal
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: EPA is proposing to exempt from Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) requirements plant-incorporated
protectants derived from plant viral coat protein genes (PVCP-PIPs)
when the PVCP-PIP meets specified criteria. EPA is proposing this
exemption because the Agency believes that the PVCP-PIPs covered by
this exemption would be of a character which is unnecessary to be
subject to FIFRA in order to carry out the purposes of the Act.
DATES: Comments must be received on or before July 17, 2007.
ADDRESSES: Submit your comments, identified by docket identification
(ID) number EPA-HQ-OPP-2006-0642, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov/.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket telephone number is (703) 305-5805.
Instructions: Direct your comments to docket ID number EPA-HQ-OPP-
2006-0642. EPA's policy is that all comments received will be included
in the docket without change and may be made available on-line at
http://www.regulations.gov, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through regulations.gov or e-
mail. The Federal regulations.gov website is an ``anonymous access''
system, which means EPA will not know your identity or contact
information unless you provide it in the body of your comment. If you
send an e-mail comment directly to EPA without going through
regulations.gov, your e-mail address will be automatically captured and
included as part of the comment that is placed in the docket and made
available on the Internet. If you submit an electronic comment, EPA
recommends that you include your name and other contact information in
the body of your comment and with any disk or CD-ROM you submit. If EPA
cannot read your comment due to technical difficulties and cannot
contact you for clarification, EPA may not be able to consider your
comment. Electronic files should avoid the use of special characters,
any form of encryption, and be free of any defects or viruses.
Docket: All documents in the docket are listed in the docket index.
Although listed in the index, some information is not publicly
available, e.g., CBI or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available either in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the OPP
Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South
Building), 2777 S. Crystal Drive, Arlington, VA. The hours of operation
of this Docket Facility are from 8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays. The Docket telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Melissa Kramer, Hazard Assessment
Coordination and Policy Division (7202M), Office of Science
Coordination and Policy, 1200 Pennsylvania Ave. NW, Washington, DC
20460-0001; telephone number: (202) 564-8497; fax number: (202) 564-
8502; e-mail address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Notice Apply to Me?
You may be potentially affected by this action if you are a person
or company involved with agricultural biotechnology that may develop
and market plant-incorporated protectants. Potentially affected
entities may include, but are not limited to:
Pesticide and Other Agricultural Chemical Manufacturing
(NAICS code 32532), e.g., establishments primarily engaged in the
formulation and preparation of agricultural and household pest control
chemicals;
Crop Production (NAICS code 111), e.g., establishments
primarily engaged in growing crops, plants, vines, or trees and their
seeds;
Colleges, Universities, and Professional Schools (NAICS
code 611310), e.g., establishments of higher learning which are engaged
in development and marketing of virus-resistant plants;
Research and Development in the Physical, Engineering, and
Life Sciences (NAICS code 54171), e.g., establishment primarily engaged
in conducting research in the physical, engineering, or life sciences,
such as agriculture and biotechnology.
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. To determine
whether you or your business may be affected by this action, you should
carefully examine the applicability provisions in 40 CFR part 174. If
you have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. What Should I Consider as I Prepare My Comments for EPA?
1. Docket. EPA has established a docket for this action under
docket identification (ID) number EPA-HQ-OPP-2006-0642. Publicly
available docket materials are available either in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the Office of Pesticide Programs (OPP) Regulatory Public
Docket in Rm. S-4400, One Potomac Yard (South Building), 2777 S.
Crystal Drive Arlington, VA. The hours of operation of this Docket
Facility are from 8:30 a.m. to 4 p.m., Monday through Friday, excluding
legal holidays. The Docket telephone number is (703) 305-5805.
[[Page 19591]]
2. Tips for preparing your comments. When submitting comments,
remember to:
i. Identify the document by docket ID number and other identifying
information (subject heading, Federal Register date, and page number).
ii. Follow directions. The Agency may ask you to respond to
specific questions or organize comments by referencing a Code of
Federal Regulations (CFR) part or section number.
iii. Explain why you agree or disagree; suggest alternatives and
substitute language for your requested changes.
iv. Describe any assumptions and provide any technical information
and/or data that you used.
v. If you estimate potential costs or burdens, explain how you
arrived at your estimate in sufficient detail to allow for it to be
reproduced.
vi. Provide specific examples to illustrate your concerns and
suggest alternatives.
vii. Explain your views as clearly as possible, avoiding the use of
profanity or personal threats.
viii. Make sure to submit your comments by the comment period
deadline identified.
II. Background
A. What Action is the Agency Proposing?
EPA is proposing an exemption from FIFRA for certain plant virus
coat protein plant-incorporated protectants or ``PVCP-PIPs.'' EPA is
proposing to define a PVCP-PIP as ``a plant-incorporated protectant
derived from one or more genes that encode a coat protein of a virus
that naturally infects plants. This includes plant-incorporated
protectants derived from one or more plant viral coat protein genes
that produce only RNA and no virus-related protein.'' PVCP-PIPs
introduced into plants with the intention of preventing or mitigating
viral disease meet the FIFRA section 2(u) definition of ``pesticide''
because they are introduced into plants with the intention of
``preventing, destroying, repelling, or mitigating any pest...'' (7
U.S.C. 136(u)) and plant viruses meet the FIFRA section 2 definition of
``pest'' (7 U.S.C. 136(t)). EPA is proposing this exemption because the
Agency believes that the PVCP-PIPs covered by this exemption would be
of a character which is unnecessary to be subject to FIFRA in order to
carry out the purposes of the Act.
A PIP can be exempt from the requirements of FIFRA, other than the
adverse effects reporting requirements of 40 CFR 174.71, if it meets
all three of the requirements listed in 40 CFR 174.21. Section
174.21(a) requires that the PIP meet the criteria listed in at least
one of the sections in Sec. Sec. 174.25 through 174.50. Section
174.21(b) requires that when the PIP is intended to be produced and
used in a crop used as food, the residues of the PIP are either
exempted from the requirement of a tolerance under FFDCA or no
tolerance would otherwise be required for the PIP. Section 174.21(c)
requires that an exempt PIP must contain only those inert ingredient(s)
included on the list codified at Sec. Sec. 174.485 through 174.490.
(Reference to Sec. Sec. 174.485 through 174.490 in Sec. 174.21(c) is
proposed to be changed to refer to Sec. Sec. 174.485 through 174.486
in today's Proposed Rule.) See Unit II.F. for further discussion of
these Sec. 174.21 criteria.
The rule proposed in today's Federal Register would establish 40
CFR 174.27, which would contain three criteria that, when met, would
allow PVCP-PIPs to meet the general requirement for exemption for all
PIPs listed at 40 CFR 174.21(a). Today's Federal Register also proposes
to add several substances known to be used as inert ingredients in PIPs
to 40 CFR part 174 subpart X, thereby potentially expanding the PVCP-
PIPs that could meet the conditions of Sec. 174.21(c). A companion
document published elsewhere in today's Federal Register also proposes
a tolerance exemption for certain PVCP-PIP residues, thereby
potentially expanding the PVCP-PIPs that could meet the conditions of
Sec. 174.21(b).
The three criteria that EPA is proposing to insert at 40 CFR 174.27
are intended to address three issues that may be associated with a
PVCP-PIP. These issues are:
The potential for increased weediness or invasiveness of
the crop plant containing the PVCP-PIP or any wild or weedy relatives
that could acquire the PVCP-PIP through gene flow thereby causing
negative effects on either the agro-ecosystem or natural environments.
This issue is addressed in proposed Sec. 174.27(a).
The potential that viruses with novel properties could
develop through novel viral interactions. This issue is addressed in
proposed Sec. 174.27(b).
The potential for human or nontarget organism exposure to
proteins that have not previously existed in nature and thus should be
examined to determine whether they have potentially toxic or allergenic
properties. This issue is addressed in proposed Sec. 174.27(c).
In order to satisfy 40 CFR 174.21(a), a PVCP-PIP would have to
satisfy proposed Sec. 174.27(a), (b), and (c). The requirements at
Sec. 174.27(d) would also have to be met to qualify for exemption.
Proposed Sec. 174.27(a), (b), and (c) each can be met in one of two
ways: a product developer may self-determine that paragraph (1) of the
criterion applies (i.e., Sec. 174.27(a)(1), (b)(1), or (c)(1)) or the
Agency may determine that paragraph (2) of the criterion applies (i.e.,
Sec. 174.27(a)(2), (b)(2), or (c)(2), respectively). Paragraph (1) of
each proposed criterion (i.e., Sec. 174.27(a)(1), (b)(1), and (c)(1))
describes an objective, well-defined characteristic. Therefore, the
developer may determine whether the PVCP-PIP meets the requirement.
Paragraph (2) of each proposed criterion (i.e., Sec. 174.27(a)(2),
(b)(2), and (c)(2)) is conditioned on an Agency determination because
it may involve analysis of several types of information. Each criterion
may be satisfied either by self determination under paragraph (1) or
Agency determination under paragraph (2) irrespective of how the other
two criteria are satisfied; there is no requirement that all three
criteria must be satisfied under either paragraph (1) or paragraph (2)
in order to qualify for the exemption.
B. What is the Agency's Authority for Taking this Action?
This rule is promulgated under the authority of FIFRA sections
3(a), 25(a), and 25(b) (7 U.S.C. 136a(a), 136w(a), and 136w(b)).
FIFRA section 3(a) states that, except as provided by the Act, no
person may distribute or sell in the United States any pesticide that
is not registered under the Act (7 U.S.C. 136(a)). FIFRA section 2(u)
defines ``pesticide'' as: ``(1) any substance or mixture of substances
intended for preventing, destroying, repelling, or mitigating any pest,
(2) any substance or mixture of substances intended for use as a plant
regulator, defoliant, or desiccant, and (3) any nitrogen
stabilizer...'' (7 U.S.C. 136(u)). Under FIFRA section 2(t), the term
``pest'' includes ``(1) any insect, rodent, nematode, fungus, weed, or
(2) any other form of terrestrial or aquatic plant or animal life or
virus, bacteria, or other microorganism... which the Administrator
declares to be a pest...'' subject to certain exceptions (7 U.S.C.
136(t)).
Before EPA may register a pesticide under FIFRA, the applicant must
show that the pesticide ``when used in accordance with widespread and
commonly recognized practice... will not generally cause unreasonable
adversese effects on the environment'' (7 U.S.C. 136a(c)(5)(D)). The
term ``environment'' includes ``water, air, land, and all plants and
man and other
[[Page 19592]]
animals living therein, and the interrelationships which exist among
these'' (7 U.S.C. 136(j)). FIFRA section 2(bb) defines the term
``unreasonable adverse effects on the environment'' to mean: ``(1) any
unreasonable risk to man or the environment, taking into account the
economic, social, and environmental costs and benefits of the use of
any pesticide, or (2) a human dietary risk from residues that result
from a use of a pesticide in or on any food inconsistent with the
standard under section 408 of the Federal Food, Drug, and Cosmetic
Act'' (7 U.S.C. 136(bb)).
Although FIFRA requires the registration of most pesticides, it
also authorizes the regulation of unregistered pesticides. FIFRA
section 3(a) provides that, to the extent necessary to prevent
unreasonable adverse effects on the environment, the Administrator may
limit the distribution, sale, or use of any pesticide that is not
registered under section 3 of FIFRA, subject to an experimental use
permit under section 5 of FIFRA, or subject to an emergency exemption
under section 18 of FIFRA. Pesticides that are ``not registered''
include pesticides that are exempt from FIFRA requirements under
section 25(b).
An unregistered pesticide may be distributed or sold if it is
exempted by regulation under FIFRA section 25(b). Under FIFRA section
25(b)(2), the Agency can exempt pesticides from some or all of the
requirements of FIFRA when the Agency determines that the pesticide is
``of a character which is unnecessary to be subject to [FIFRA] in order
to carry out the purposes of this Act'' (7 U.S.C. 136w(b)(2)). EPA
interprets section 25(b)(2) to authorize the Agency to exempt a
pesticide or category of pesticides that EPA determines (1) poses a low
probability of risk to the environment and (2) is not likely to cause
unreasonable adverse effects to the environment even in the absence of
regulatory oversight under FIFRA. This standard differs from the
standard for registration which considers only whether the pesticide
``when used in accordance with widespread and commonly recognized
practice... will not generally cause unreasonable adverse effects on
the environment'' (7 U.S.C. 136a(c)(5)(D)).
In evaluating the first condition that must be met for the Agency
to exempt a pesticide, i.e., whether use of the pesticide poses a low
probability of risk to the environment, EPA considers the extent of the
potential risks caused by use of the pesticide to the environment,
including humans and other animals, plants, water, air and land.
Potential risks to humans include dietary risks as well as non-dietary
risks such as those resulting from occupational or residential exposure
to the pesticide. EPA uses the FFDCA section 408 standard in evaluating
dietary risks as discussed in Unit II.C. of this preamble. EPA will not
exempt pesticides unless they pose a low probability of risk to the
environment.
In evaluating the second condition that must be met for the Agency
to exempt a pesticide, i.e., whether the use of the pesticide is
unlikely to cause unreasonable adverse effects on the environment even
in the absence of regulatory oversight under FIFRA, EPA balances all
the potential risks to human health, including dietary risks (see Unit
II.C. of this preamble for discussion of the FFDCA standard), and risks
to the remainder of the environment from use of the pesticide against
the potential benefits associated with its use. In balancing risks and
benefits, EPA considers the economic, social, and environmental costs
and benefits of the use of the pesticide. If the pesticide poses a low
probability of risk to the environment and is not likely to cause
unreasonable adverse effects to the environment even in the absence of
regulatory oversight under FIFRA, EPA may exempt the pesticide from
regulation under FIFRA.
C. What is the Relationship of FIFRA Exemptions to the FFDCA Section
408 Standard?
Under FFDCA section 408(a), a pesticide chemical residue in or on a
food (hereafter simply ``in food'') is not considered safe unless EPA
has issued a tolerance for the residue and the residue is within the
established tolerance limit or EPA has issued an exemption from the
requirement of a tolerance for the residue (21 U.S.C. 346a(a)(1)).
FFDCA section 408 authorizes EPA to determine a residue is safe and
therefore exempt from the requirement of a tolerance if the
Administrator ``has determined that there is a reasonable certainty
that no harm will result from aggregate exposure to the pesticide
chemical residue, including all anticipated dietary exposures and all
other exposures for which there is reliable information'' (21 U.S.C.
346a(c)(2)(A)(ii)). Section 408 of the FFDCA also directs EPA to
specifically consider harm that may result to infants and children as a
result of pesticide chemical residues. For additional discussion of
this standard, see the Exemption from the Requirement of a Tolerance
under the Federal Food, Drug, and Cosmetic Act for Residues of Plant
Virus Coat Proteins that are Part of a Plant-Incorporated Protectant
published concurrently in today's Federal Register.
EPA uses the FFDCA section 408 safety standard in evaluating
whether a pesticide used in food meets the FIFRA section 25(b)(2)
exemption standard with respect to human dietary risk. A pesticide in
food poses a low probability of human dietary risk if it meets the
FFDCA section 408 standard for an exemption from the requirement of a
tolerance. Such a pesticide also is not likely to cause unreasonable
adverse effects to the environment, with respect to human dietary risk
only, if the dietary risks resulting from use of that pesticide are
consistent with the FFDCA section 408 exemption standard, and the
potential benefits of use outweigh any dietary risk even in the absence
of regulatory oversight.
FIFRA, however, does not provide for exemption of a pesticide in
food based solely upon human dietary risk and consistency with the
FFDCA section 408 exemption standard; an exemption from the
requirements of FFDCA does not exempt a product from regulation under
FIFRA. For an exemption under FIFRA, EPA must also evaluate non-dietary
risks to humans and the remainder of the environment from the pesticide
and determine both that the pesticide poses only a low probability of
non-dietary risks and that use of the pesticide is not likely to cause
any unreasonable adverse effects to the environment from such
nondietary risks in the absence of regulation.
D. What is the Role of Other Federal Agencies?
EPA is the Federal agency responsible for the regulation of
pesticides. Under the Coordinated Framework for Regulation of
Biotechnology (51 FR 23302, June 26, 1986), EPA works closely with the
U.S. Department of Agriculture (USDA), which has responsibilities under
the Plant Protection Act (PPA), and the U.S. Food and Drug
Administration (FDA), which has responsibilities under FFDCA. EPA,
USDA, and FDA consult and exchange information when such consultation
is helpful in resolving safety questions. The three agencies also
strive for consistency between programs following one of the basic
tenets of the Coordinated Framework, i.e., that the agencies composing
the Framework adopt consistent approaches to the extent permitted by
the respective statutory authorities. A consistent approach between
agencies is easier for the regulated community to understand, and it
likely conserves resources
[[Page 19593]]
because data developed for one agency may meet at least some of the
requirements posed by another agency for the same or similar products.
1. USDA. USDA has the responsibility of preventing the introduction
and dissemination of plant pests under the PPA. Before a genetically
engineered plant that is subject to the PPA may be introduced into the
environment, approval must be obtained from the USDA/Animal Plant
Health Inspection Service (APHIS) unless such a plant has been reviewed
and granted Nonregulated Status. The USDA regulations use genetic
engineering and potential plant pest risk as criteria for determining
the scope of its regulations (62 FR 23945, May 2, 1997). Any
genetically engineered plant that contains genetic material from a
plant pest is subject to the regulations. Thus, all plants containing
PVCP-PIPs are subject to USDA/APHIS requirements under the PPA.
EPA therefore recognizes that there is a potential for duplicative
oversight with respect to certain issues that may arise in decisions
about PVCP-PIPs that require any review by EPA. For example, in its
reviews of Petitions for Determination of Nonregulated Status under
regulations at 7 CFR part 340, the potential for weediness, for
displacement of native species, and potential consequences of gene
transfer are evaluated by USDA/APHIS. EPA and USDA/APHIS will continue
to consult and collaborate on reviews of PVCP-PIPs. EPA and USDA/APHIS
will work together to avoid potential duplication and inconsistencies
and to coordinate their analyses in accordance with their respective
expertise and jurisdiction.
2. FDA. FDA is the primary U.S. agency responsible for ensuring the
safety of commercial food and food additives. FDA's authority under
FFDCA extends to any nonpesticidal substance that may be introduced
into a new plant variety and that is expected to become a component of
food. Pursuant to sections 201 and 408 of FFDCA and the creation of
EPA, pesticide chemical residues are subject to EPA's regulatory
authority under FFDCA.
E. What is a PVCP-PIP?
EPA is proposing to define a PVCP-PIP as ``a plant-incorporated
protectant derived from one or more genes that encode a coat protein of
a virus that naturally infects plants. This includes plant-incorporated
protectants derived from one or more plant viral coat protein genes
that produce only RNA and no virus-related protein.''
Coat proteins are those substances that viruses produce to
encapsulate and protect the viral nucleic acid and to perform other
important tasks for the virus, e.g., assistance in viral replication,
movement within the plant, and transmission of the virus from plant to
plant by insects (Ref. 1). In many cases, when the genetic material
encoding a plant virus coat protein is engineered into a plant's
genome, the plant displays resistance to infection by that virus as
well as other viruses having similar coat protein sequences (Ref. 2).
Current scientific information suggests that prevention or
mitigation of disease by PVCP-PIPs may occur by two different
mechanisms. For some PVCP-PIPs, resistance is believed to be protein-
mediated because efficacy is correlated with the concentration of coat
protein produced by the transgene (Ref. 3). In protein-mediated
resistance, the coat protein is thought to impede the infection cycle
by interfering with the disassembly of infecting viruses (Ref. 4).
In transgenic plants, a second mechanism of resistance, post-
transcriptional gene silencing (PTGS) may be activated. In PTGS,
prevention or mitigation of viral disease is not correlated with the
level of coat protein expression. Indeed, virus resistance can occur
even when a coat protein gene expresses untranslatable RNA sequences
and no coat protein is detected (Ref. 4). PTGS is a defense mechanism
in plants against foreign RNA (e.g., viruses) in which sequence-
specific RNA degradation is initiated by the plant in response to the
foreign RNA itself. Evidence suggests that PTGS is initiated once there
is a threshold accumulation of double-stranded (ds) RNA in the cell
cytoplasm (Ref. 5). Over 90% of plant viruses have single-stranded RNA
genomes, but viral replication transiently produces dsRNA in quantities
sufficient to trigger PTGS (Ref. 6). PTGS is also known to occur with
transgenes that are transcribed at a low level but that likely produce
dsRNA (Ref. 7). Once the plant recognizes the dsRNA, it is thought to
be cleaved by a dsRNA-specific nuclease to produce small 21- to 25-
nucleotide short interfering RNA sequences (siRNAs; Ref. 8). The siRNAs
are thought to serve as guides for the cleavage of single-stranded RNA
with a sequence similar to the dsRNAs (Ref. 9). Thus once PTGS is
initiated, it targets all RNA with high sequence similarity to the
sequence that initiated the process, regardless of whether it was
transcribed from the transgene, an endogenous gene, or viral RNA.
A plant virus coat protein transgene that confers virus resistance
through either a protein- or RNA-mediated mechanism would fall within
EPA's proposed definition of a PVCP-PIP. The substances involved in
either mechanism of resistance would meet the FIFRA definition of a
pesticide because the transgene and any material expressed from the
transgene are introduced into a plant for the purpose of preventing or
mitigating viral disease (see Unit II.A.).
The proposed definition of a PVCP-PIP contains the phrase
``naturally infects plants.'' Including this phrase in the definition
would specifically limit the proposed exemption by requiring that the
virus coat protein gene sequence used in the PVCP-PIP be based
exclusively on a plant virus sequence. This limitation is proposed in
order to exclude from the definition any coat proteins of plant viruses
that have been modified with sequences from animal or human viruses.
EPA includes this concept in today's proposal in response to comment
received from the public in earlier Federal Register documents
pertaining to PVCP-PIPs.
F. What Conditions Must be Met for a PVCP-PIP to Qualify for a FIFRA
Exemption?
As noted above, a PIP is exempt from the requirements of FIFRA,
other than the adverse effects reporting requirements of 40 CFR 174.71,
if the PIP meets the requirements in 40 CFR 174.21(a), (b), and (c).
Therefore, the following factors need to be considered to determine the
FIFRA status of a PVCP-PIP. First, does the PVCP-PIP meet the
requirement at 40 CFR 174.21(a)? Second, do the residues of the PVCP-
PIP meet the requirement at 40 CFR 174.21(b)? Third, do the inert
ingredients that are part of the PVCP-PIP meet the requirement at 40
CFR 174.21(c)?
1. Does the PVCP-PIP meet the requirement at 40 CFR 174.21(a)?
Section 174.21(a) requires that the PIP meet the criteria listed in at
least one of the sections in Sec. Sec. 174.25 through 174.50. Today's
action proposes to establish Sec. 174.27, which would contain criteria
allowing certain PVCP-PIPs to meet the Sec. 174.21(a) requirement for
exemption. These criteria identify those PVCP-PIPs that EPA has been
able to determine meet the standard under FIFRA section 25(b)(2), i.e.,
that pose a low probability of risk to the environment and that are not
likely to cause unreasonable adverse effects to the environment even in
the absence of regulatory oversight under FIFRA. EPA is proposing
criteria that address the
[[Page 19594]]
relevant potential risks associated with these products:
i. The potential for increased weediness or invasiveness of the
crop plant containing the PVCP-PIP or any wild or weedy relatives that
could acquire the PVCP-PIP through gene flow thereby causing negative
effects on either the agro-ecosystem or natural environments. This
issue is addressed at Sec. 174.27(a) and is referred to as
``weediness'' for the purposes of this document.
ii. The potential for viruses with novel properties developing
through novel viral interactions. This issue is addressed at Sec.
174.27(b) and is referred to as ``viral interactions'' for the purposes
of this document.
iii. The potential for human or nontarget organism exposure to
proteins that may not have previously existed in nature and thus should
be examined to determine whether they have potentially toxic or
allergenic properties. This issue is addressed at Sec. 174.27(c) and
is referred to as ``protein production'' for the purposes of this
document.
Proposed Sec. Sec. 174.27(a), (b), and (c) are discussed in
greater detail in Unit III of this Federal Register document. In
addition, a graphical depiction of what this rule is proposing is
available in the docket for this proposed rule.
2. Do the residues of the PVCP-PIP meet the requirement at 40 CFR
174.21(b)? Section 174.21(b) requires that in order to qualify for a
FIFRA exemption, the residues of a PVCP-PIP that is intended to be
produced and used in a crop used as food must either be exempted from
the requirement of a tolerance under FFDCA or no tolerance would
otherwise be required for the PVCP-PIP. Therefore, if a PVCP-PIP is
used in a food plant (e.g., the PVCP-PIP is produced and used in a corn
plant) or residues of the PVCP-PIP might reasonably be expected in food
(e.g., the PVCP-PIP is produced and used in an ornamental plant but
could move through gene flow to a sexually compatible food plant), the
FFDCA section 408 requirements must be considered when determining
whether the PVCP-PIP can be exempted under FIFRA. If a PVCP-PIP would
not be used in and would not reasonably be expected in a crop used as
food (e.g., the PVCP-PIP is produced and used in an ornamental plant
with no sexually compatible relatives that are food plants), the FFDCA
section 408 requirements do not need to be considered.
EPA anticipates that in most cases the PVCP-PIP residues will
consist of residues of nucleic acids, residues of inert ingredients,
and residues of the plant virus coat protein portion of the PVCP-PIP
(the ``PVC-protein''). Residues of nucleic acids are exempt from the
requirement of a tolerance at 40 CFR 174.475. As of the time this
proposed rule is being issued, residues of those inert ingredients that
are exempt from the requirement of a tolerance are listed at 40 CFR
part 180 and 40 CFR part 174 subpart W. In a companion piece appearing
in today's Federal Register, EPA is proposing a tolerance exemption for
residues of certain PVC-proteins that meet specified criteria. Due to
different statutory requirements, the proposed FFDCA exemption criteria
differ from the criteria proposed in this Federal Register for 40 CFR
174.27 under FIFRA.
3. Do the inert ingredients that are part of the PVCP-PIP meet the
requirement at 40 CFR 174.21(c)? Section 174.21(c) requires that in
order for a PIP to qualify for exemption any inert ingredient contained
in the PIP must be codified at subpart X of 40 CFR part 174 - List of
Approved Inert Ingredients. Subpart X lists the inert ingredients (i)
that may be used in a plant-incorporated protectant listed in subpart B
(Exemptions) of part 174 and (ii) whose residues are either exempted
from the requirement of a tolerance under FFDCA or no tolerance would
otherwise be required. EPA is proposing to add several substances known
to be used commonly as inert ingredients in PIPs to 40 CFR part 174
subpart X. These substances already have tolerance exemptions under
FFDCA. EPA proposes in today's Federal Register that these substances,
when used in exempt PIPs as inert ingredients under specified
conditions, should also be exempt from FIFRA because they are of a
character which is unnecessary to be subject to FIFRA in order to carry
out the purposes of the Act.
G. What if a PVCP-PIP Does Not Qualify for Exemption?
If EPA is unable to conclude that a PVCP-PIP meets the standard for
exemption, an applicant may still apply to register the PVCP-PIP under
section 3 of FIFRA. EPA may be able to conclude that the PVCP-PIP meets
the standard for registration (i.e., when it is used in accordance with
widespread and commonly recognized practice, it will not generally
cause unreasonable adverse effects on the environment). EPA recognizes
that the proposed exemption criteria may not identify all low risk
PVCP-PIPs. A case-by-case review for registration would allow the
Agency to evaluate factors not readily incorporated into clear,
unambiguous exemption criteria. As part of registration, the Agency
could also impose conditions of use as appropriate. As is EPA's general
practice regarding registration of PIPs, the Agency will consult with
USDA in evaluating PVCP-PIPs for registration.
H. What is the History of this Proposal?
1. Scientific input. EPA sponsored or cosponsored with other
Federal agencies, six conferences relevant to development of this
proposed rule: on October 19-21, 1987, a meeting on ``Regulatory
Considerations: Genetically Engineered Plants'' at Cornell University
in Ithaca, New York; on September 8-9, 1988, a ``Transgenic Plant
Conference'' in Annapolis, Maryland; on November 6-7, 1990, a
conference on ``Pesticidal Transgenic Plants: Product Development, Risk
Assessment, and Data Needs'' in Annapolis, Maryland; on April 18-19,
1994, a ``Conference on Scientific Issues Related to Potential
Allergenicity in Transgenic Food Crops'' in Annapolis, Maryland; on
July 17-18, 1997, a ``Plant Pesticide Workshop'' in Washington, DC; and
on December 10-12, 2001 a conference on ``Assessment of the Allergenic
Potential of Genetically Modified Foods'' in Chapel Hill, North
Carolina. EPA incorporated information from these conferences in
development of this proposed rule as appropriate.
EPA has requested the advice of two scientific advisory bodies at
five meetings while developing its approach to plant-incorporated
protectants. On December 18, 1992, EPA convened a FIFRA Scientific
Advisory Panel (SAP) to review a draft policy on PIPs (then called
plant-pesticides) and to respond to a series of related questions posed
by the Agency dealing primarily with EPA's approach under FIFRA. On
July 13, 1993, EPA requested the advice of a Subcommittee of the EPA
Biotechnology Science Advisory Committee (BSAC) on a series of
scientific questions dealing with EPA's approach to PIPs under FFDCA.
On January 21, 1994, EPA asked for advice on the Agency's approach to
PIPs under both statutes at a joint meeting of the SAP and the BSAC. To
evaluate more recent scientific advances, EPA again brought these
issues to a FIFRA SAP meeting on October 13-14, 2004. On December 6-8,
2005, EPA convened a SAP meeting to address a series of scientific
questions related to this proposal. EPA incorporated advice from all
five meetings in development of this proposed rule as appropriate.
2. Federal Register documents. The history of this proposal
consists of the original proposed exemption from
[[Page 19595]]
FIFRA requirements that appeared in the November 23, 1994 Federal
Register (59 FR 60519); the original proposed exemption from FFDCA
tolerance requirements in the November 23, 1994 Federal Register (59 FR
60545); and several supplemental documents appearing in the May 16,
1997 Federal Register (59 FR 27149), the July 22, 1996 Federal Register
(61 FR 37891), the April 23, 1999 Federal Register (64 FR 19958), and
the July 19, 2001 Federal Register (66 FR 37772 and 37855).
i. November 23, 1994. In a document that appeared in the November
23, 1994 Federal Register (59 FR 60519) (FRL-4755-3), EPA proposed two
alternatives under FIFRA section 25(b)(2) to exempt PVCP-PIPs from
FIFRA requirements. Option 1 proposed to categorically exempt plant-
pesticides derived from coat proteins from plant viruses (now called
PVCP-PIPs). Option 2 proposed a more limited exemption covering only
those PVCP-PIPs that would have the least potential to confer selective
advantage on free-living wild relatives of the plants that could
acquire the PVCP-PIP through gene flow (discussed in detail in Unit
III.C.3.).
Elsewhere in the November 23, 1994, Federal Register (59 FR 60545)
(FRL-4755-4), EPA proposed to exempt from the FFDCA requirement of a
tolerance, residues of plant virus coat proteins produced and used in
living plants as a plant-incorporated protectant (then called a plant-
pesticide). The proposed exemption from the requirement of a tolerance
read, ``Residues of coat proteins from plant viruses, or segments of
the coat proteins, produced in living plants as plant-pesticides are
exempt from the requirement of a tolerance'' (59 FR 60547).
ii. May 16, 1997. In August of 1996, Congress enacted the Food
Quality Protection Act (FQPA), which amended FFDCA and FIFRA. On May
16, 1997, EPA published a supplemental document in the Federal Register
(62 FR 27149) (FRL-5716-6) to provide the public with an opportunity to
comment on EPA's analysis of how certain FQPA amendments to FFDCA and
FIFRA applied to the 1994 proposed exemption from the requirement of a
tolerance for residues of viral coat proteins produced in plants as
part of a PIP. (Today's Federal Register terms such entities ``PVC-
proteins.'')
In the 1997 supplemental document, EPA explained how most of the
substantive factors that the amended FFDCA requires EPA to consider in
evaluating pesticide chemical residues had been considered in the
Agency's 1994 proposed tolerance exemption. Even though the Agency may
not have used the terminology specified in the FQPA, EPA did take into
account most of the factors (e.g., toxicity and consumption patterns)
in issuing its 1994 proposal to exempt residues of PVC-proteins, or
residues of segments of such proteins, from FFDCA tolerance
requirements. EPA therefore sought comment on the requirements imposed
by FQPA that the Agency had not addressed in its 1994 proposal,
specifically:
a. EPA's conclusion that there are no substances outside of the
food supply that may have a cumulative toxic effect with residues of
PVC-proteins,
b. EPA's conclusion that there are no substances outside of the
food supply to which humans might be exposed through non-occupational
routes of exposure that are related via a common mechanism of toxicity
to residues of PVC-proteins,
c. Any available information on PVC-proteins causing estrogenic
effects,
d. EPA's rationale, described in greater detail, for concluding
that PIPs are likely to present a limited exposure of pesticidal
substances to humans in which the predominant route of exposure will be
dietary, and
e. EPA's rationale, described in greater detail, for concluding
that the Agency's analysis concerning the dietary safety of food
containing PVC-proteins applies to infants and children as well as
adults.
Because of the 1996 FQPA, EPA's final determination under FIFRA for
PVCP-PIPs in food plants could also be affected by comments on the
companion document in today's Federal Register that proposes a
tolerance exemption for certain PVCP-PIP residues.
iii. July 22, 1996. On July 22, 1996, EPA issued a supplemental
document (61 FR 37891) (FRL-5387-4) requesting comment on one aspect of
its November 23, 1994 Federal Register document: how the concept of
inert ingredient related to plant-incorporated protectants.
iv. April 23, 1999. On April 23, 1999, EPA published a supplemental
document in the Federal Register (64 FR 19958) (FRL-6077-6) soliciting
comment on whether to change the name of pesticides produced and used
in living plants.
v. July 19, 2001. In July of 2001, EPA published a package of
notices related to PIPs in the Federal Register, including a
supplemental document (66 FR 37855) (FRL-6760-4) that provided the
public with additional opportunity to comment on the FIFRA and FFDCA
exemptions for PIPs that the Agency proposed in 1994 but had not yet
finalized by 2001. EPA also requested comment on the information,
analyses, and conclusions pertaining to these PIPs (including PVCP-
PIPs) contained in the NRC report entitled ``Genetically Modified Pest-
Protected Plants: Science and Regulation'' (Ref. 10). The public was
given an opportunity to comment on a proposal to clarify the language
of the original 1994 proposals EPA was considering in response to
public comment received on the 1994 proposal. In addition, the Agency
requested additional public comment on several scientific issues. Also
in the July 19, 2001 Federal Register (66 FR 37772) (FRL-6057-7), EPA
changed the name of these pesticides from ``plant-pesticides'' to
``plant-incorporated protectants'' or ``PIPs.''
The documents and reports of the meetings described above,
including associated public comments, are available in the public
dockets established for the associated rulemakings as described in Unit
IX of this preamble.
Today's proposed rule completely supersedes these previous
proposals. EPA does not intend to respond to comments submitted on
those proposals. Thus, individuals who believe that any comments
submitted on any of the earlier proposals remain germane to today's
proposal, should submit them (or relevant portions) again during this
comment period.
III. Proposed Exemption Criteria under Sec. 174.27
A. Structure of the Proposed Exemption Criteria under Sec. 174.27
In order to satisfy the general requirement for a FIFRA exemption
listed at 40 CFR 174.21(a), EPA is proposing to add three criteria at
40 CFR 174.27. As discussed in Unit II.F.1., the three criteria that
EPA is proposing to adopt at 40 CFR 174.27 are intended to address
three issues that are associated with potential risks of PVCP-PIPs.
The PVCP-PIP would have to meet proposed Sec. Sec. 174.27(a), (b),
and (c) to satisfy 40 CFR 174.21(a). Proposed Sec. Sec. 174.27(a),
(b), and (c) each can be met in one of two ways: a product developer
may self-determine that paragraph (1) of the criterion is met (i.e.,
Sec. 174.27(a)(1), (b)(1), or (c)(1)) or the Agency may determine that
paragraph (2) of the criterion is met (i.e., Sec. 174.27(a)(2),
(b)(2), or (c)(2), respectively). Paragraph (1) of each proposed
criterion (i.e., Sec. 174.27(a)(1), (b)(1), and (c)(1)) describes an
objective, well-defined characteristic. Therefore, the developer may
determine whether the PVCP-PIP meets the requirement. Paragraph (2) of
[[Page 19596]]
each proposed criterion (i.e., Sec. 174.27(a)(2), (b)(2), and (c)(2))
is conditioned on an Agency determination because several types of
information may need to be evaluated using a weight-of-evidence
approach to determine whether the PVCP-PIP meets the requirement and is
therefore of a nature warranting exemption.
1. Exemption by self-determination. Each criterion may be satisfied
under either paragraph (1) or paragraph (2) irrespective of how the
other two criteria are satisfied; there is no requirement that all
three criteria must be satisfied under either paragraph (1) or
paragraph (2) in order for a PVCP-PIP to qualify for the exemption.
However, if a PVCP-PIP satisfies all three criteria under paragraph (1)
by developer self determination (i.e., it meets proposed Sec. Sec.
174.27(a)(1), (b)(1), and (c)(1)) and it satisfies Sec. Sec. 174.21(b)
and (c), EPA is proposing that the developer submit a notification to
the Agency of that determination and certify that the PVCP-PIP
qualifies for exemption under FIFRA, i.e., that the PVCP-PIP meets
Sec. Sec. 174.21(a), (b), and (c). In addition, EPA is proposing that
the developer maintain information adequate to support the
determination. Such records must be made available for EPA inspection
and copying or be otherwise submitted to the Agency for review upon
request for the duration of time that the PVCP-PIP is sold or
distributed. EPA is proposing that these records be kept so that EPA
could review a particular exemption determination if needed at a future
date.
EPA is proposing to require that the notifications contain:
i. The name of the crop (including genus and species) containing
the PVCP-PIP.
ii. The name of the virus from which the coat protein gene was
derived.
iii. The name of the virus(es) to which resistance is conferred.
iv. When available, a unique identifier.
EPA is proposing this notification requirement because it provides
a mechanism that allows the Agency to keep a record of all PVCP-PIPs
that may be sold or distributed. EPA expects that such a list would be
useful to developers whose products are moving in international trade
because it would enable EPA to post information on the United States
Regulatory Agencies Unified Biotechnology Website (found at http://usbiotechreg.nbii.gov/database_pub.asp) indicating that the developer
has determined that the product satisfies the Agency's safety
requirements. Such information can facilitate acceptance by importing
countries. Absent such a posting, the field for EPA information would
be blank, and importers might question the regulatory status of the
product in the United States. In addition, EPA considers that such a
list may be useful to the Agency for ensuring enforcement and
compliance with FIFRA regulations because it will enable compliance
personnel to ascertain the exemption status of products encountered in
distribution and trade channels.
2. Exemption by Agency determination. If a PVCP-PIP does not
satisfy a particular criterion under paragraph (1) (i.e., Sec.
174.27(a)(1), (b)(1), or (c)(1)), EPA proposes that as an alternative
route to exemption, the product developer would submit data or other
information to the Agency to demonstrate that a particular PVCP-PIP
meets paragraph (2) of that criterion (i.e., it meets Sec.
174.27(a)(2), (b)(2), or (c)(2), respectively). In addition, as part of
this submission, a developer would also include a certification as to
any determination that the product meets Sec. 174.27(a)(1), (b)(1),
and/or (c)(1), as appropriate. During its review under Sec.
174.27(a)(2), (b)(2), and/or (c)(2), EPA would not review the
developer's determination that the product met any criterion under
Sec. 174.27(a)(1), (b)(1), or (c)(1).
EPA expects that in many instances developers would have most, if
not all the information that would need to be included in any exemption
submission under Sec. Sec. 174.27(a)(2), (b)(2), or (c)(2) because it
would have been gathered in the course of product development or for
submission to USDA/APHIS as part of a petition for determination for
non-regulated status. EPA will consult with USDA in evaluating whether
a PVCP-PIP meets the conditions for an Agency-determined exemption. EPA
is proposing that information supporting the submission be maintained
as records that will be available for EPA inspection as necessary for
the duration of time that the PVCP-PIP is sold or distributed.
EPA will evaluate the information contained in the submission and
publish a notice allowing the public to comment on the Agency's
determination that a product meets Sec. 174.27(a)(2), (b)(2), and/or
(c)(2), as appropriate. EPA is providing such a public comment period
because even though the public will have had the opportunity to comment
through this proposal on the appropriateness of the criteria in Sec.
174.27(a)(2), (b)(2), and (c)(2), the public would not otherwise have
an opportunity to comment on whether a particular PVCP-PIP meets these
criteria, given that these determinations depend on a case-by-case
analysis of several types of information.
The Agency plans to publish a Federal Register notice announcing
its determination that a PVCP-PIP meets Sec. 174.27(a)(2), (b)(2),
and/or (c)(2), and if no adverse comments are received during the
comment period, the Agency's decision will be considered final, and EPA
will publish no further notice. Based on its experience with EUP
notices, EPA expects that, in general, determinations that a PVCP-PIP
qualifies for exemption will be noncontroversial and generate no
adverse comments. However, in the case of adverse comments, EPA would
publish a subsequent Federal Register notice announcing its final
determination and address all public comments. EPA would prefer
criteria in Sec. 174.27(a)(2), (b)(2), and (c)(2) that would allow the
public and PVCP-PIP developers to readily predict the outcome of an
Agency review. Such criteria would reduce regulatory uncertainty in
PVCP-PIP development and decrease the time EPA would need to evaluate
the data/information necessary to make a determination that a PVCP-PIP
meets a given criterion. However, using criteria for which
determinations can be readily predicted might reduce the number of
PVCP-PIPs that would qualify for exemption. EPA tried to balance these
concerns and proposed multiple options when the Agency was unsure how
to resolve this dilemma.
However, EPA does not believe that the considerations underlying
its decisions to grant the public a further opportunity to comment on
the Agency's decision apply in cases where the Agency rejects a
submission for an exemption. Accordingly, if EPA determines that the
product fails to meet one or more of the exemption criteria, EPA will
provide notice to the applicant of its decision on the submission and
that a registration would be required for the PVCP-PIP before the PVCP-
PIP could be sold or distributed. The product developer may then submit
an application for registration to the Agency. EPA would evaluate such
PVCP-PIPs under the existing registration process and could implement
conditions of use as appropriate.
B. Key Scientific Issues Associated with the Proposed Exemption
Criteria under Sec. 174.27
Several scientific questions concerning risk issues associated with
PVCP-PIPs have been identified:
What is the potential for a PVCP-PIP to endow plants with
characteristics
[[Page 19597]]
that could disrupt the existing network of ecological relationships in
managed, semi-managed, or natural ecosystems, e.g., through gene
transfer to wild or weedy\1\ relatives? This issue is addressed at
proposed Sec. 174.27(a) and is referred to as ``weediness'' for the
purposes of this discussion.
---------------------------------------------------------------------------
\1\ In the context of the phrase ``wild and weedy'' relatives/
plants used throughout this preamble, EPA considers weedy plants to
be those with the characteristics of weeds, i.e., those that are
considered undesirable, unattractive, or troublesome, especially
when growing where they are not wanted. Wild plants are those that
occur, grow, and live in a natural state and are not domesticated,
cultivated, or tamed. EPA considers a naturalized population to be
an enduring population of domesticated plants that grows in wild
(non-cultivated) areas. EPA considers a native plant population to
be one that originates in a particular region or ecosystem.
---------------------------------------------------------------------------
What is the potential for interactions between a PVCP-PIP
and an infecting virus to affect plant virus epidemiology or
pathogenicity? This issue is addressed at proposed Sec. 174.27(b) and
is referred to as ``viral interactions'' for the purposes of this
discussion.
What is the potential for exposure of humans or nontarget
organisms to PVC-proteins with novel toxic or allergenic properties?
This issue is addressed at proposed Sec. 174.27(c) and is referred to
as ``protein production'' for the purposes of this discussion.
These three questions are addressed below under the headings of
weediness, viral interactions, and protein production, respectively.
C. Weediness
1. Scientific issues. In evaluating whether a PVCP-PIP could alter
ecological relationships among plants, EPA considered two primary
issues: (1) whether the PVCP-PIP could endow a transgenic plant itself
with an increased ability to spread into natural or semi-managed
habitats and (2) whether the transfer of a PVCP-PIP from a transgenic
plant into wild or weedy relatives could endow the wild or weedy
relative with increased competitive ability and thus disrupt ecological
relationships. Gene transfer among sexually compatible plants is a
natural phenomenon that EPA does not consider to be an environmental
risk per se. Whether the transfer of a PVCP-PIP could significantly
disrupt ecological relationships in specific instances depends on all
of the following considerations: First, does the crop plant containing
the PVCP-PIP have wild relatives with which it is able to hybridize in
nature? If it does not, there can be no gene transfer. Second, if there
are sexually compatible relatives, is the gene conferring virus
resistance likely to become stable in the population? Third, is the
stable introduction of a PVCP-PIP into the plant population (i.e.,
introgression) likely to cause the population to become more weedy/
invasive or otherwise alter its competitive ability, thereby
significantly changing the population dynamics of the plant community?
The 2005 SAP concurred that these are important considerations for
PVCP-PIPs by noting that an ``important ecological risk associated with
gene flow from crop plants into their wild relatives is that the
acquisition of crop genes might substantially alter the population
dynamics of the wild plant. In particular, a transgene introgressed
from the crop relative into a wild population might allow the wild
species to persist in larger populations across a larger geographic
range, or in a wider range of habitats. Collectively these changes in
population dynamics can be considered `increased weediness'. The
probability that a particular transgene will lead to increased
weediness depends on the phenotype conferred by the transgene and on
the ecological factor(s) currently limiting the size or distribution of
the wild species. In particular, if the transgene alters plant response
to the ecological factor limiting population size, then population
dynamics may be affected. For PVCP-PIPs, the relevant consideration is
whether virus resistance (conferred by the PVCP-PIP) leads to changes
in the size or distribution of wild plant species with the PVCP-PIP''
(Ref. 11).
i. Likelihood that a crop plant containing a PVCP-PIP could itself
disrupt ecological relationships. In considering whether a PVCP-PIP
could affect the ability of a plant to spread into natural or semi-
managed habitat at the margins of cultivated fields, i.e., to form
feral or naturalized populations, the key consideration is whether
viral infection is currently limiting the ability of agricultural crops
to do so. The 2005 SAP pointed out that PVCP-PIPs ``are developed when
virus infection of a crop reduces the crop yield, suggesting that virus
infection is quite likely in naturalized populations of the crop as
well'' (Ref. 11). However, virus infection in crop plants does not
necessarily limit the spread of the crop into natural or semi-managed
areas. As the 2005 Panel also noted, ``little is known about factors
controlling population size in plant populations in general, including
those that are currently stable, as well as those that are currently
weedy or invasive'' (Ref. 11). Few published studies are available that
evaluate this question directly, perhaps due to the general rarity of
negative results in scientific literature. However, one study did find
virus infection to have little effect on an agricultural crop. Field
experiments with transgenic virus-resistant sugar beets revealed no
competitive advantage (measured as seedling emergence and biomass
production) between the transgenic and susceptible control lines (Ref.
12).
Although virus infection has been shown to negatively impact growth
and/or reproduction of some natural plant communities (discussed below
in Unit III.C.1.ii.), EPA recognizes that there is reason to question
whether the situation would be different for crop plants. The National
Research Council (NRC) noted in 1989 that most naturalized,
domesticated crops generally are unable to effectively compete with
wild species in natural ecosystems and have not been known to acquire
this ability with the type of single-gene traits commonly introduced
through genetic modification (Ref. 13). The 1989 NRC report went on to
note that plant breeders have capitalized for decades on the fact that
relatively minor genetic changes can produce plants with altered
ecological properties, but the addition of pest resistant traits has
not been known to result in increased weediness of widely used crops
(Ref. 13). A 1989 survey of the weedy characteristics of crop versus
weed species showed that weeds possess significantly more weedy
characteristics on average than do crop plants (Ref. 14). For
domesticated crops, the traits that make them useful to humans also
reduce their competitive ability in nonagricultural habitats. Crops
that have been subjected to long-term breeding (e.g., corn and
soybeans) are unlikely to possess characteristics that would allow the
plant to compete effectively outside of managed ecosystems. Domesticity
arises because intensive breeding efforts seek to eliminate many
characteristics of the crop plant that would enhance weediness (e.g.,
seed shattering, thorns, seed dormancy, and bitterness). For example,
lack of seed shattering and seed dormancy greatly reduces the ability
of an annual crop to persist without human intervention. Highly
domesticated crops such as corn are thus unlikely to survive for
multiple generations outside agricultural fields no matter what
transgenic trait they contain, including virus resistance (Ref. 15).
However, some crop species, e.g., cranberry and blackberry may have
more similarities to their wild relatives than highly domesticated
crops such as corn or soybean. As noted by the 2005
[[Page 19598]]
SAP, ``Determining whether a particular crop can naturalize and then
spread as a weedy species is difficult to ascertain from the literature
and determining the probability that a crop will be more weedy or
invasive if it contains a PVCP-PIP is even more difficult'' (Ref. 11).
Such determinations may therefore need to rely on information not
available in public literature as part of a risk assessment for a
particular plant. Plants, such as forest trees, that may grow for many
years in natural environments or in very close proximity to natural
environments present additional difficulty in evaluating and managing
risks (Ref. 16). The period of time over which such plants would
persist is significantly longer than for annual, short-lived species.
Individual plants will therefore experience a much wider range and
variety of stress conditions, enemy attacks, and climate change, making
predictions about naturalization potential with acquired virus
resistance particularly challenging.
Thus, although EPA believes that many crop species are unlikely to
disrupt ecological relationships through acquisition of a PVCP-PIP, the
available information is insufficient to support the general
conclusions that EPA would need to make for a categorical exemption of
PVCP-PIPs. EPA would need to conclude that there is a low risk that
acquisition of a PVCP-PIP would significantly affect the
competitiveness of any of the plants currently grown as crops and that
none of these crop species would significantly disrupt ecological
relationships when modified to contain a PVCP-PIP. Therefore, the
Agency believes that it is necessary to evaluate each plant species
independently to consider whether it is likely to establish weedy or
invasive populations outside of agricultural fields in the United
States and thereby potentially significantly disrupt ecological
relationships if it becomes virus resistant due to a PVCP-PIP. Factors
likely to influence this determination cannot be readily distilled into
a straightforward criterion suitable for a categorical exemption.
ii. Likelihood that a crop plant containing a PVCP-PIP could
significantly disrupt ecological relationships through gene transfer.
The question of whether gene transfer from a crop to a wild or weedy
relative could significantly disrupt ecological relationships is a more
complicated question because a much broader range of potential plants
may be involved when wild or weedy relatives are considered in addition
to the crops themselves. The answer to this question depends first on
the question of whether the transgenic crop plants could transfer a
PVCP-PIP to other plant populations. This potential for transfer
depends in part on the frequency of hybridization between domesticated
species and their wild relatives. Hybridization is affected by the
ability of plants to cross-pollinate which in turn is affected by their
timing of reproductive viability and the proximity of the plants.
Hybridization is also affected by the ability of pollen to fertilize
recipient plants, the recipient plants to develop viable seeds, these
seeds to germinate, and the seedlings to grow into viable adults (Ref.
17). In spite of these potential constraints, a survey of the world's
most important crops suggests that spontaneous hybridization of
domesticated plants with wild relatives appears to be a general feature
across at least a portion of the worldwide geographic area over which
each is cultivated (Refs. 18 and 19). The ability to cross crops with
wild relatives (which may not necessarily occur where the crop is
grown) is also the basis of many traditional breeding techniques that
are used for virtually all crops (Ref. 20).
Whether virus infection limits the growth and/or reproductive
ability of wild or weedy plant populations is more difficult to answer
generically for all plants in all ecosystems. Viruses are pervasive in
many natural plant populations (Refs. 21, 22, 23, and 24), although a
comprehensive body of literature on the effect of viruses in weed
species is lacking. According to the 2004 SAP, ``Our knowledge about
the effect of virus infection on non-crop plants is quite limited''
(Ref. 25). Some published studies report that virus infection can have
little or no effect on the plants. For example, a survey of Plantago
species in England showed that although 92 of 144 plants were infected
with one or more viruses, most of the plants showed no obvious disease
symptoms (Ref. 23). A literature review of the role of weeds in the
occurrence and spread of plant virus diseases describes several cases
where viruses significantly damage certain crops but have little effect
on their weed hosts (Ref. 26).
Other published studies have reported that infection reduces plant
growth and/or fecundity. For example, naturally occurring tobacco leaf
curl virus infection increases mortality and has negative effects on
growth and seed output in plants from wild populations of the flowering
perennial plant Eupatorium chinense (Ref. 27). Greenhouse experiments
with this same plant under two irradiance levels showed that virus
infection did not affect survivorship under high-light conditions but
caused severe damage under low-light conditions (Ref. 28). Vegetative
growth and flower production of purslane (Portulaca oleracea) was also
reduced when plants were inoculated with cucumber mosaic virus (Ref.
29). Field experiments showed that wild cabbage plants (Brassica
oleracea) inoculated with turnip mosaic virus or turnip yellow mosaic
virus have reduced survival, growth, and reproduction (Ref. 30). Such
experiments suggest that viruses can sometimes reduce individual plant
growth and/or fecundity when infection occurs. However, individual-
level effects are insufficient to understand population-level
processes. For example, even if virus disease significantly affected
individual plant fitness, a decline in individual-plant fitness might
reduce competition such that uninfected plants could increase
reproductive output, thereby mitigating any population-level effects
(Ref. 31).
It can be difficult to predict the actual impact on overall plant
population dynamics that would result from acquisition of virus
resistance by plants that are in some way negatively affected by virus
infection. EPA is not aware of any published study that has directly
examined this question by, for example, purposefully freeing a plant
species from virus infection and investigating the resulting population
dynamics of infected versus uninfected plants. The 2004 SAP was also
unaware of any such study, but offered that ``[b]ased on knowledge
obtained from observation of cultivated crops in the agroecosystem, the
majority of the Panel concluded that it would be unlikely that a plant
population freed from viral pressure would give a plant species a
competitive advantage'' (Ref. 25). Some members of the 2005 SAP agreed
with the 2004 SAP, while ``[o]ther members of the current [2005] SAP
believed, based on new information (Fuchs et al. 2004; Sukopp et al.,
2005) not available to the 2004 Panel, as well as EPA indicating a lack
of data on this topic, that concluding that viruses typically have no
effect on their wild plant hosts is not accurate. Because of the
differing opinions among the current [2005] Panelists, and the general
paucity of data, the Panel cautioned that further research is needed to
provide stronger support to this particular issue'' (Refs. 11, 32, and
33). EPA also notes that evaluating impacts on plant population
dynamics is further complicated because in certain cases gene transfer
of a PVCP-PIP to wild or weedy relatives might potentially be
desirable. For example, an invasive virus species might be
[[Page 19599]]
effectively controlled through broad acquisition of resistance by plant
species susceptible to the virus. Controlling disease outbreaks in
perennial agricultural plants and trees could be significantly aided by
reducing viral load in the environment through such approaches.
A few studies are available that are relevant to the question of
whether acquisition of virus resistance could affect plant population
dynamics. These studies show that in some cases virus infection can
have such effects, suggesting that acquired virus resistance might as
well. For example, infection with alfalfa mosaic virus substantially
diminished the ability of certain medic cultivars to compete with other
species such as capeweed in grazed pasture swards, both directly by
decreasing the competitive ability of infected plants, and indirectly
by altering the proportions in which the species germinated (Ref. 34).
In another example of virus infection affecting plant population
dynamics, growth analysis of Eupatorium makinoi revealed that plants
naturally infected with a geminivirus had significantly reduced stem
growth and plant height, along with decreased flowering and
survivorship. This study suggests that in spite of the long-term
coexistence of the virus and Eupatorium makinoi, such negative fitness
attributes have a significant impact on at least some local plant
populations in this species (Ref. 35).
Although relatively little research has been published regarding
how plant population dynamics are directly influenced by virus
infection, such results as described in the previous paragraph provide
some support for the premise that virus resistance might be an
important ecological fitness characteristic. At least some plant
populations acquiring virus resistance might in some instances be able
to better compete against other species (Ref. 36) and/or spread to
habitats previously unsuitable because of the presence of the virus
(Ref. 37). For example, a broad survey of geographic data on plant
associations with viruses from published compendia and governmental or
academic databases showed that plants were infected by 24% fewer
viruses in their naturalized ranges than in their native ranges,
supporting the hypothesis that the impact of invasive plants results in
part from reduced natural enemy (e.g., virus) attack (Ref. 38). On the
other hand, enemy release is only one of many hypotheses that could
explain the abundance and/or impact of an invasive plant (Ref. 39). In
addition, a few published studies have reported that in certain
instances virus infection can increase plant fitness, suggesting that
acquisition of virus resistance might decrease plant fitness. For
example, infection by barley yellow dwarf virus was found in at least 1
year to increase the fitness of the host plant green foxtail (Setaria
viridis) by approximately 25% (Ref. 40). In some cases, plants might be
more attractive to herbivores when not infected by viruses, as was
found to be the case for dusky coral pea (Kennedya rubicunda; Ref. 41).
In this experiment, caged rabbits presented with a mixture of carrots
and powdered plant extract grazed the mixture made from virus-free
plant material at twice the rate as plant material infected with
Kennedya yellow dwarf virus due presumably to greater palatability. In
general, negative fitness attributes would be expected to be selected
against in populations. Nevertheless, such considerations might be
important in certain instances, e.g., when evaluating possible effects
on endangered species.
EPA believes it likely that many of the potential PVCP-PIP/plant
combinations pose a low risk of disrupting the existing network of
ecological relationships in semi-managed or natural ecosystems.
Multiple conditions must be met to pose a higher level of risk, i.e.,
hybridization with a wild relative must occur, introgression of the
gene must occur, and acquired virus resistance must confer an advantage
(or disadvantage) to the recipient plant sufficient to alter plant
population dynamics. Nevertheless, the research discussed above showing
that in some cases viruses can affect plant population dynamics for at
least some plants highlights the difficulty in drawing a general
conclusion as to whether all PVCP-PIP/plant combinations are likely to
pose a low risk of significantly disrupting existing ecological
networks. Virtually any crop could be modified to contain a PVCP-PIP,
including less domesticated forage crops and trees, and such a wide
range of plants will be associated with a concomitantly wide range of
characteristics and behaviors. Ecosystems are highly complex and
variable, and some of the factors that limit fitness of a given plant
species can be subtle and are not well understood (Ref. 15).
Consequently, EPA does not believe that the available body of evidence
would currently support a definitive conclusion for all PVCP-PIPs that
the potential transfer to wild or weedy relatives presents a low risk
of significantly altering the network of ecological relationships in
semi-managed or natural ecosystems.
Information may be available to evaluate the likelihood of acquired
virus resistance impacting a particular plant species or population.
However, the existing body of literature currently does not appear
sufficient to describe any set of circumstances that would predict for
the wide variety of possible PVCP-PIP/plant combinations whether
introgression of the PVCP-PIP into a wild or weedy relative could
change the population dynamics of the recipient plant and through this
route potentially affect ecological relationships with other plants and
other organisms in the community. For example, it is not possible to
predict a priori whether a possible fitness advantage that individual
plants might acquire with a PVCP-PIP would make the plant population
better able to compete against other species. Whether population
dynamics would be affected and ecological relationships could be
disrupted in a given circumstance is dependent on multiple, interacting
factors. In some instances, a weight-of-evidence, case-by-case review
of information such as experimental data might allow such a
determination; however, general knowledge of factors likely to
influence population dynamics cannot be readily distilled into a
straightforward criterion suitable for a categorical exemption.
2. Proposed exemption criterion. EPA is proposing Sec. 174.27(a)
based on a set of considerations articulated by the 2005 SAP to
identify plants that would not pose concerns associated with increased
weediness of either the crop plant itself or any sexually-compatible
wild relatives, if the crop plant were to contain a PVCP-PIP. Section
174.27(a)(1) is a categorical exemption criterion for a subset of PVCP-
PIPs, i.e., a list of plants that have already been determined by the
Agency to be low risk with respect to concerns associated with
weediness irrespective of the particular PVCP-PIP the plants might
contain. Section 174.27(a)(2) is a conditional exemption criterion
based on Agency review of whether a particular plant/PVCP-PIP
combination poses low risk with respect to concerns associated with
weediness. Both parts of Sec. 174.27(a) are discussed in more detail
in Units III.E.1.iii. and III.E.1.iv. below. Note that a PVCP-PIP
qualifies for exemption based in part on its presence in a particular
crop species. The record on which this proposed exemption is based is
not currently broad enough to support an exemption for a PVCP-PIP in
another species if that species has not been evaluated for concerns
associated with weediness when it contains a particular
[[Page 19600]]
virus-resistant trait. A PVCP-PIP that has been moved into another
species does not qualify for the exemption unless the recipient plant
appears on the list in Sec. 174.27(a)(1). Such a PVCP-PIP would either
need an individual exemption determination under Sec. 174.27(a)(2) or
a registration in order to be sold or distributed.
i. Proposed categorical exemption criterion in Sec. 174.27(a)(1).
As articulated above, EPA does not believe it can propose a categorical
exemption based on whether a PVCP-PIP/plant combination is likely to
result in changes in plant population dynamics because this endpoint
cannot easily be predicted based on straightforward characteristics of
the PVCP-PIP and/or plant. However, EPA believes that a criterion for a
categorical exemption could be developed based on evaluation of
individual crop species for their potential to naturalize and invade
natural ecosystems, including with acquisition of a PVCP-PIP and for
the existence of wild or weedy relatives that could acquire a PVCP-PIP
through gene flow. Certain plants are expected to pose low risk with
respect to concerns associated with weediness regardless of any
particular PVCP-PIP that the species contained. However, for the
categorical exemption, the Agency is attempting to identify those
situations where no case-by-case review is necessary to conclude that a
PVCP-PIP would present a low risk of causing adverse effects. In such
situations, a product developer could use a clearly defined criterion
to make a determination of status. Based on these considerations, EPA
has developed a list of plants that the Agency proposes a developer
could use to self-determine whether Sec. 174.27(a) is met.
A PVCP-PIP would meet proposed Sec. 174.27(a) under Sec.
174.27(a)(1) if the plant containing the PIP is one of the following:
Anthurium (Anthurium spp.), asparagus (Asparagus officinale), avocado
(Persea americana), banana (Musa acuminata), barley (Hordeum vulgare),
bean (Phaseolus vulgaris), cacao (Theobroma cacao), carnation (Dianthus
caryophyllus), chickpea (Cicer arietinum), citrus (Citrus spp., e.g.,
Citrus aurantifolia, Citrus limon, Citrus paradisii, Citrus sinensis),
coffee (Coffea arabica and Coffea canephora), corn (Zea maize), cowpea
(Vigna unguiculata), cucumber (Cucumis sativus), gerbera (Gerbera
spp.), gladiolus (Gladiolus spp.), lentil (Lens culinaris), mango
(Mangifera indica), orchids (Orchidaceae), papaya (Carica papaya), pea
(Pisum sativum), peanut (Arachis hypogaea), pineapple (Ananas comosus),
potato (Solanum tuberosum), soybean (Glycine max), starfruit (Averrhoa
carambola), sugarcane (Saccharum officinarum), or tulips (Tulipa spp.).
EPA developed this list of plants after consultations with both the
2004 and 2005 SAPs. The 2004 SAP recommended a longer list of plants,
chosen initially based on the presumption that they had no wild or
weedy relatives in the United States. However, the 2005 SAP noted that
the longer list of plants recommended by the 2004 SAP clearly contained
``some species that form viable crop-wild hybrids...'' (Ref. 11).
Recognizing that much of the most useful information is not likely to
be found in the literature, ``the Panel recommended consulting
agronomists, breeders, and/or ecologists with specialized expertise
before including any crop on a list of exempt species'' (Ref. 11). The
2005 Panel also recommended a specific set of conditions that each
species would have to meet based on the advice of such experts (i.e.,
agronomists, breeders, and/or ecologists with specialized expertise) if
it were to be placed on the list:
1. A crop should be included on the exempt list if it forms no
viable hybrids with wild or weedy relatives anywhere in the US...
2. A crop should...be included on the exempt list only if it is
[not] currently weedy or invasive...
3. A crop should be included on the exempt list if... it will
not establish weedy or invasive populations if it becomes virus
resistant (due to a PVCP-PIP)...
4. If a PVCP-PIP crop has the potential to naturalize, but the
PVCP-PIP transgene is in biocontainment and/or biomitigation
constructs that are stacked such that escapes from cultivation are
too unfit to compete with the wild type, a consensus of breeders,
agronomists, and ecologists, or others with experience with the
species could advise addition to the list (Ref. 11).
EPA believes that the first three conditions proposed by the 2005
SAP are useful factors in evaluating whether a plant warrants inclusion
on the list in Sec. 174.27(a)(1). EPA considered each of these factors
when evaluating each of the plants currently on the list in proposed
Sec. 174.27(a)(1). However, EPA also recognizes that plants that do
not strictly meet condition 1 as laid out by the SAP may nevertheless
be determined to pose low risk with respect to weediness concerns after
a case-by-case review of the plants' traits and consideration of the
whole range of factors that affect weediness. For example, corn may not
meet the first condition above as articulated by the SAP if it proves
to in fact have wild relatives in some region of the United States with
which it can form viable hybrids. However, as discussed below, EPA does
not believe that the characteristics of the wild relatives or the
hybrids that could be formed suggest any reason to suspect acquired
virus resistance would change the weediness potential of corn, the
hybrid, or the wild relative, and EPA therefore proposes to include
corn on the list. Thus, in practice EPA considers the 2005 SAP's first
three conditions as a useful guide of the factors that should be taken
into account in evaluating whether to include a plant on the list.
However, EPA believes that relying on a strict interpretation of these
conditions would exclude many plants containing PVCP-PIPs that meet
FIFRA's low risk standard. The 2005 SAP itself suggested that some
flexibility of interpretation might be appropriate. Although the Panel
used the phrase ``no viable hybrids'' in condition 1, the Panel
elsewhere recommended against granting exemption to crops with
``sexually compatible wild relatives'' where ``sexually compatible
refers to the possibility of having crop transgenes backcross and
introgress into the relative; it does not refer to sterile hybrids''
(Ref. 11).
Although EPA considered the first three conditions proposed by the
2005 SAP in deciding whether to include a particular plant species on
the list in Sec. 174.27(a)(1), EPA believes that the fourth condition
as articulated would be inappropriate for these purposes. A
biocontainment and/or biomitigation construct would be associated with
a particular PVCP-PIP, not a particular plant species. The intent of
Sec. 174.27(a)(1) is to list species that would not present concerns
related to weediness regardless of the particular PVCP-PIP that the
species contained. EPA believes that construct-specific considerations
could be taken into account under an Agency review procedure such as
that described below in Unit III.C.2.iii.
The Panel recommended ``consulting agronomists, breeders, and/or
ecologists with specialized (taxon-specific) expertise on weedy
populations before including any crop on a list of exempt species''
because this information ``is difficult to ascertain from the
literature and determining the probability that a crop will be more
weedy or invasive if it contains a PVCP-PIP is even more difficult.''
Likewise, the Panel indicated ``[i]t is very difficult to identify
crops that have no sexually compatible wild or weedy relatives in the
US or its possessions and that do not become weedy or invasive
themselves. This information is unique to each crop, is often not
published, and is often known only by the agronomists, breeders, and
[[Page 19601]]
ecologists working with the specific taxa in question'' (Ref. 11). EPA
agrees that such information is difficult to obtain from the literature
and therefore relied on written consultation with such experts in
evaluating whether the three conditions proposed by the 2005 SAP had
been met for a particular crop species.
In consulting with experts for a particular crop, EPA asked at
least three individuals a series of questions designed to address the
issues identified by the 2005 SAP as relevant for evaluating whether a
PVCP-PIP would be low risk with respect to concerns associated with
weediness if it were to be found in the particular species.
Specifically, EPA wanted to know:
Does this crop form viable hybrids in nature (i.e.,
without human intervention) with wild or weedy relatives in the United
States (including Puerto Rico, the Virgin Islands, Guam, the Trust
Territory of the Pacific Islands, and American Samoa)?
If yes, what species are they? Which of these species are
themselves commercially grown crops? What is the frequency of hybrid
production? Have hybrids demonstrated enhanced fitness (vigor) relative
to parental varieties? Can the hybrids reproduce asexually? Are the
hybrids sexually fertile?
If hybrids are sexually fertile, will they outcross or only
backcross with the crop parent? How does the phenology of the crop
species compare with the phenology of plant(s) with which it is
sexually compatible? Are there any other attributes of these species
that may enhance or inhibit sexual reproduction and species out-
crossing?
Is this crop known to become feral or easily spread into
non-crop areas in the United States (including Puerto Rico, the Virgin
Islands, Guam, the Trust Territory of the Pacific Islands, and American
Samoa)? If yes, have escaped plants formed reproducing and sustaining
populations in non-crop areas? Where has this been known to happen?
With what frequency is this likely to occur? Have feral populations
required weed management activity?
How likely is it that this crop would become feral or
easily spread into non-crop areas if it acquired transgenic resistance
to one or more viruses? What is the basis for your answer?
EPA focused these questions on ``non-crop areas'' to emphasize that
the key consideration is a crop's behavior in natural settings. EPA
recognizes that most crops within agricultural fields form volunteer
populations, where propagules of the crop from the previous rotation
grow in the subsequent crop rotation. The Agency did not consider
behavior in crop areas when evaluating the crops for inclusion on the
list at proposed Sec. 174.27(a)(1).
The responses to specific Agency-posed questions received from
these expert consultations are available in the docket for this
proposed rule (Ref. 42). EPA considered the experts' responses in
conjunction with other information when determining whether to list a
crop at proposed Sec. 174.27(a)(1), as discussed below. Crops that EPA
evaluated but did not include in the proposed list for one reason or
another are discussed in Unit VII where comment on these crops is
specifically requested.
EPA notes that the 2005 SAP also suggested the Agency ``consider
the geographic distribution of crops and their wild relatives when
considering potential exemptions'' (Ref. 11). Although this is a
potential option the Agency could pursue, a number of considerations
limit the utility of using the potential for geographic isolation in
determining whether a plant could be included on the list in Sec.
174.27(a)(1). For example, EPA would need to consider carefully whether
such isolation is likely to remain throughout the commercial life of
the PVCP-PIP. Such isolation could occur if the crop containing the
PVCP-PIP would not be commercially viable in the areas where wild
relatives occur given biological considerations that are unlikely to
change. However, geographic isolation could also be due to factors that
may change throughout the commercial life of a PVCP-PIP, e.g.,
individual farmer choices of which crops to plant. Because of such
considerations, EPA anticipates that it would only be able to support
an exemption dependant on geographic restrictions where biological or
similar factors provide assurance that the geographic isolation will
remain constant during the entire commercial life of the PVCP-PIP.
The next several Subunits summarize EPA's conclusions to include
the crops listed at proposed Sec. 174.27(a)(1) based on consideration
of the conditions suggested by the 2005 SAP and their recommendation
that evaluation of these conditions be done in consultation with
breeders, agronomists, and ecologists familiar with the particular
species. The analyses below indicate that there is an extremely low
probability that virus resistance conferred through a PVCP-PIP in any
of these plants would significantly alter existing plant population
dynamics or existing ecological relationships. The list is
straightforward, providing an easy-to-understand criterion.
Accordingly, EPA is proposing that a developer may self-determine
whether a PVCP-PIP meets this criterion, i.e., whether the plant
containing the PVCP-PIP is on the proposed list, because no further
data or information would be needed to evaluate whether ecological
relationships could be disrupted through increased weediness when the
plant modified to contain the PVCP-PIP is on the list.
a. Anthurium. EPA proposes that anthurium (Anthurium spp.) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with anthurium experts. These consultations indicate that anthurium
meets the three conditions outlined above by the SAP: It does not have
wild or weedy relatives in the United States with which it can form
viable hybrids in nature, it is not currently weedy or invasive in the
United States, and there is no reason to believe that acquisition of
virus resistance would make anthurium weedy or invasive. All three
experts contacted by EPA indicated agreement with these statements. For
example, one expert stated, ``The commercial species [of] Anthurium
(Anthurium schezerianum and Anthurium andraenum) have been grown
outdoors since the early 1900's in semi-tropical and tropical areas of
the US and there are no records of any commercial species escaping and
becoming feral into non-crop areas. There is no reason to believe that
acquiring transgenic resistance to one or more viruses would increase
the ability of plants to become feral or easily spread into non-crop
areas'' (Ref. 42). EPA therefore believes that anthurium meets the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
b. Asparagus. EPA proposes that asparagus (Asparagus officinale) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with asparagus experts. These consultations indicate that asparagus
meets the three conditions outlined above by the SAP. One, it does not
have wild or weedy relatives in the United States with which it can
form viable hybrids in nature. One expert said, ``Although volunteer
asparagus plants may grow ``wild'' (i.e., not intentionally
cultivated), they are not typically considered to be weeds. There are
several horticultural varieties of asparagus, which could potentially
be cross-pollinated. However, considering that asparagus is insect
pollinated, this is likely to occur only in the rare situation where an
asparagus grower also is growing horticultural varieties'' (Ref. 42).
Second, the experts agreed that asparagus is not currently weedy or
invasive outside of agricultural fields in
[[Page 19602]]
the United States. Two of the three experts indicated that asparagus
can infrequently become feral. However, ``[a]sparagus is not typically
considered to be a weedy species. In addition, since asparagus has
separate male and female plants, it is considerably more difficult for
``wild'' populations to become established. Asparagus is also a
relatively slow growing plant such that eradication (if necessary)
would not be particularly onerous'' (Ref. 42). Third, these experts
agreed that it is unlikely that acquisition of virus resistance would
make asparagus weedy or invasive. For example, one expert stated, ``I
have worked with this crop since 1978 and in all those years, I have
not observed asparagus to become easily spread at all in non-crop or
crop areas. Although asparagus does rarely grow wild in some areas
(usually the temperate zones) asparagus is a very poor competitor with
weeds and other plants and asparagus requires much attention and
cultural care to thrive. I have only viewed a very rare occassionaly
[sic] plant along fence rows and they usually are very weak and non-
vigorous. Acquired transgenic resistance would do nothing to affect
asparagus to become feral'' (Ref. 42). EPA therefore believes that
asparagus meets the conditions recommended by the 2005 SAP for
inclusion on the list and will present low risk with respect to
weediness.
c. Avocado. EPA proposes that avocado (Persea americana) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with avocado experts. These consultations indicate that avocado meets
the three conditions outlined above by the SAP: It does not have wild
or weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make avocado weedy or invasive. All three experts
contacted by EPA indicated agreement with these statements. For
example, one expert stated ``Transgenic resistance should not affect
the likelihood of spread. Viral susceptibility is not an important
factor limiting the plant's ability to become feral'' (Ref. 42). EPA
therefore believes that avocado meets the conditions recommended by the
2005 SAP for inclusion on the list and will present low risk with
respect to weediness.
d. Banana. EPA proposes that banana (Musa acuminata) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with banana
experts. These consultations indicate that banana meets the three
conditions outlined above by the SAP: It does not have wild or weedy
relatives in the United States with which it can form viable hybrids in
nature, it is not currently weedy or invasive in the United States, and
there is no reason to believe that acquisition of virus resistance
would make banana weedy or invasive. All three experts contacted by EPA
indicated agreement with these statements. For example, one expert
stated ``[i]t is highly unlikely that banana with acquired transgenic
resistance would spread to non-crop areas because the probability of
crossing is extremely small. Through vegetative propagation it will
require man [sic] intervention just as non-transgenic plants'' (Ref.
42). EPA therefore believes that banana meets the conditions
recommended by the 2005 SAP for inclusion on the list and will present
low risk with respect to weediness.
e. Barley. EPA proposes that barley (Hordeum vulgare) be included
on the list in Sec. 174.27(a)(1) based on EPA consultations with
barley experts. These consultations indicate that barley meets the
three conditions outlined above by the SAP: It does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make barley weedy or invasive, as viruses are not
consistently associated with failure of barley to show any evidence of
being weedy or invasive. Three experts contacted by EPA indicated
agreement with these statements. For example, one expert stated that he
believes the likelihood that barley would become feral or easily spread
into non-crop areas if it acquired transgenic virus resistance is
``negligible. Barley has been cultivated for decades in many U.S.
environments, including environments that impose relatively mild
disease pressure, particularly for viral diseases, such as the upper
midwest and western states, and barley has not been able to establish
itself in those regions as a feral species'' (Ref. 42). EPA notes that
the 2005 SAP indicated that ``barley can hybridize with Hordeum
jubatum, which is a weed in the USA'' (Ref. 11). However, three barley
breeders consulted about this specific issue did not agree that
hybridization was likely to occur. One stated, ``In relation to Hordeum
vulgare subsp. Vulgare (cultivated barley) Hordeum jubatum is in the
tertiary genepool. This means crossability is extremely difficult event
under laboratory conditions'' (Ref. 42). A study that attempted to
cross barley with two wild relatives, H. murinum L. and H. jubatum L.,
found that no hybridization occurred, even under favorable greenhouse
conditions with forced pollination (Ref. 43). EPA therefore believes
that barley meets the conditions recommended by the 2005 SAP for
inclusion on the list and will present low risk with respect to
weediness.
f. Bean. EPA proposes that bean (Phaseolus vulgaris) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with bean
experts. These consultations indicate that bean meets the three
conditions outlined above by the SAP. One, it does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature. One expert mentioned that ``[h]ybrids between
Phaseolus vulgaris and Phaseolus acutifolius (tepary bean) are only
achieved through extensive crossing and embryo rescue and thus is
highly unlikely to occur in nature'' (Ref. 42). Another expert said
bean would ``only - but rarely - hybridize with wild vulgaris (only
where wild vulgaris occur, generally not in [the United States] & there
are often biological barriers to such occurring'' (Ref. 42). Second,
these experts agreed that bean is not currently weedy or invasive in
the United States. Third, these experts agreed that it is unlikely that
acquisition of virus resistance would make bean weedy or invasive. For
example, one expert stated, ``Viruses generally do not prevent
susceptible beans from making a crop (just the yield and quality of the
crop is greatly reduced'' (Ref. 42). EPA therefore believes that bean
meets the conditions recommended by the 2005 SAP for inclusion on the
list and will present low risk with respect to weediness.
g. Cacao. EPA proposes that cacao (Theobroma cacao) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with cacao
experts. These consultations indicate that cacao meets the three
conditions outlined above by the SAP: It does not have wild or weedy
relatives in the United States with which it can form viable hybrids in
nature, it is not currently weedy or invasive in the United States, and
there is no reason to believe that acquisition of virus resistance
would make cacao weedy or invasive. All three experts contacted by EPA
indicated agreement with these statements. For example, one expert
stated that ``cacao is difficult to cultivate, the seeds are very
susceptible to desiccation, and germination must occur within a few
days or the seed die [sic]'' (Ref. 42). EPA therefore believes that
cacao meets the conditions
[[Page 19603]]
recommended by the 2005 SAP for inclusion on the list and will present
low risk with respect to weediness.
h. Carnation. EPA proposes that carnation (Dianthus caryophyllus)
be included on the list in Sec. 174.27(a)(1) based on EPA
consultations with carnation experts. These consultations indicate that
carnation meets the three conditions outlined above by the SAP. One, it
does not have wild or weedy relatives in the United States with which
it can form viable hybrids in nature. Two, it is not currently weedy or
invasive in the United States. One expert indicated that Arkansas and
Massachusetts have populations of feral Dianthus caryophyllus. However
these have not required management activity because ``populations have
remained small consisting of only a few plants'' (Ref. 42). Three,
there is no reason to believe that acquisition of virus resistance
would make carnation weedy or invasive. One expert stated, ``Most
species of Dianthus are self-incompatible, and commercial selections of
carnation require hand pollination, and set little viable seed. There
is no record of carnation, D. caryophyllus, being naturalized or
invasive in any part of the world'' (Ref. 42). EPA therefore believes
that carnation meets the conditions recommended by the 2005 SAP for
inclusion on the list and will present low risk with respect to
weediness.
i. Chickpea. EPA proposes that chickpea (Cicer arietinum) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with chickpea experts. These consultations indicate that chickpea meets
the three conditions outlined above by the SAP: It does not have wild
or weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make chickpea weedy or invasive. All three experts
contacted by EPA indicated agreement with these statements. For
example, one expert stated that ``there is no chance that chickpea
would become feral with or without virus resistance. The susceptibility
of the seeds to rotting without seed treatment would prevent any spread
to non-crop areas. Resistance to viruses would not affect this
outcome'' (Ref. 42). EPA therefore believes that chickpea meets the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
j. Citrus. EPA proposes that citrus (Citrus spp.) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with citrus
experts. These consultations indicate that citrus meets the three
conditions outlined above by the SAP. One, it does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature. One expert mentioned that citrus can hybridize with
other Citrus species and certain other closely related species in the
sub-family Aurantioidea. However, this expert also noted that it was
unlikely to hybridize naturally with any of these species that are
found in the United States because they are not closely related and
``would only be in the tertiary genepool for citrus'' (Ref. 42).
Another expert pointed out that Rangpur lime is sometimes mentioned as
native to Florida, but he did not think this was true; as far as he
knew, there are no wild or weedy relatives of citrus found in the
United States. Second, these experts agreed that citrus is not
currently weedy or invasive in the United States. One expert mentioned
that there are ``small feral populations of citrus found in Florida,
mostly on the borders of the Everglades area and in some old
forests.... However, these populations have not expanded their range. I
know of no weed management efforts'' (Ref. 42). Third, these experts
agreed that it is unlikely that acquisition of virus resistance would
make citrus weedy or invasive. For example, one expert stated that
``citrus is simply not an aggressive grower with or without a virus''
(Ref. 42). EPA therefore believes that Citrus species meet the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
k. Coffee. EPA proposes that coffee (Coffea arabica and Coffea
canephora) be included on the list in Sec. 174.27(a)(1) based on EPA
consultations with coffee experts. These consultations indicate that
both species of coffee meet the three conditions outlined above by the
SAP: They do not have wild or weedy relatives in the United States with
which they can form viable hybrids in nature, they are not currently
weedy or invasive in the United States, and there is no reason to
believe that acquisition of virus resistance would make coffee weedy or
invasive. All three experts contacted by EPA indicated agreement with
these statements. For example, one expert stated, ``Coffee plantations
that are abandoned usually decay and are not overtaken by coffee
plants. The crop needs maintenance to grow properly. It is not a weedy
species'' (Ref. 42). EPA therefore believes that coffee meets the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
l. Corn. EPA proposes that corn (maize; Zea mays) be included on
the list in Sec. 174.27(a)(1) based on EPA's extensive experience
regulating PIPs in corn (Ref. 44), literature that is available on corn
biology, the OECD Consensus Document on the Biology of Zea mays subsp.
mays (Maize) (Ref. 45), and EPA consultations with corn experts (Ref.
42). OECD consensus documents are written by national experts who
freely consult with breeders, agronomists, and ecologists who are
specialists in the field. Each document must be reviewed and approved
by experts in the 30 OECD member countries, and often by experts from
non-OECD member countries. This body of information indicates that corn
is low risk with respect to concerns associated with weediness.
EPA's 2001 risk assessment for Bt PIPs evaluated the potential for
corn to form viable hybrids with wild or weedy relatives in the United
States (Ref. 44). EPA's summary conclusion was that while wild
relatives of corn (i.e., Eastern Gama Grass and teosintes) may exist in
the United States, there is no significant risk of gene capture and
expression of a PIP in any of these relatives. The potential for
pollen-directed gene flow from corn to Eastern Gama Grass is extremely
remote. This is evidenced by the difficulty with which Tripsacum
dactyloides x Zea mays hybrids are produced in structured breeding
programs. Additionally, the genus does not represent any species
considered as serious or pernicious weeds in the United States or its
territories. Any introgression of genes into this species as a result
of cross fertilization with genetically modified corn is not expected
to result in a species that is weedy or difficult to control. In many
instances where hybridization has been directed between these two
species, the resultant genome is lacking in most or all of the corn
chromosomal complement in subsequent generations. Many of the Zea
species loosely referred to as ``teosintes'' will produce viable
offspring when crossed with Zea mays ssp. mays. None of these plants
are known to harbor weedy characteristics, and none of the native
teosinte species, subspecies, or races are considered to be aggressive
weeds in their native or introduced habitats. In fact, many are on the
brink of extinction where they are indigenous and will be lost without
human intervention (i.e., conservation measures). Two of the three
experts EPA consulted indicated that corn will not form viable hybrids
with any wild or weedy relatives in the United States.
[[Page 19604]]
The third indicated that hybrids could be formed with teosintes, but
that a hybrid ``would lose its seed dispersal ability, so would have
highly diminished ability to propagate in the wild. In regions where
teosinte is a weed (mostly in Mexico), the teosintes have been
naturally selected to have `gametophyte factors' (e.g., Ga1-s, Tcb1),
that essentially block corn pollen from fertilizing teosinte'' (Ref.
42).
Further, the body of information and the experts that EPA consulted
on corn indicate that it is not currently weedy or invasive in the
United States. None of the landraces or cultivated lines of Zea mays
are considered to have weedy potential, and all are generally
considered to be incapable of survival in the wild as a result of
breeding practices (i.e., selection) during domestication of the crop.
According to the OECD consensus document, ``[m]aize has lost the
ability to survive in the wild due to its long process of
domestication, and needs human intervention to disseminate its seed.
Although corn from the previous crop year can overwinter and germinate
the following year, it cannot persist as a weed'' (Ref. 45). One expert
EPA consulted stated, ``Maize does not become feral or spread easily
into non-crop areas in the United States or its territories. During its
domestication many centuries ago, maize lost many of the attributes
necessary to sustain itself in nature'' (Ref. 42).
Finally, there is no reason to believe that acquisition of virus
resistance would make corn weedy or invasive, as viruses are not
consistently associated with failure of corn to show any evidence of
being weedy or invasive. The experts EPA consulted agree that corn's
becoming weedy with acquisition of a PVCP-PIP is unlikely. For example,
one expert indicated, ``Domesticated maize has no seed dispersal
mechanism. Humans are required to remove kernels from the cob (a
typical cob holds 500-1,000 kernels, which would essentially try to all
grow in the same spot, this would starve the resulting plants for
nutrients and water and result in there being no progeny). Maize would
essentially die out within a year or two, without human intervention''
(Ref. 42). EPA therefore believes that corn meets the conditions
recommended by the 2005 SAP for inclusion on the Sec. 174.27(a)(1)
list and will present low risk with respect to weediness.
m. Cowpea. EPA proposes that cowpea (black-eyed pea; Vigna
unguiculata) be included on the list in Sec. 174.27(a)(1) based on EPA
consultations with cowpea experts. These consultations indicate that
cowpea meets the three conditions outlined above by the SAP. One, it
does not have wild or weedy relatives in the United States with which
it can form viable hybrids in nature. One expert indicated, ``the
cowpea is a highly self-pollinating crop that rarely outcrosses with
other cowpeas. I expect that it might be possible for cowpea to rarely
outcross with a `wild' V. unguiculata, but it is probably safe to
assume that the `wild' cowpea genotypes don't exist in the United
States'' (Ref. 42). Second, the experts agreed that cowpea is not
currently weedy or invasive outside of agricultural fields in the
United States. One expert said, ``I am not aware of any instance where
the cowpea has become feral or easily spread into non-crop areas in the
United States. HOWEVER, I am aware of instances where cultivated cowpea
varieties have become weed pests in cultivated areas in the United
States where OTHER CROPS are grown. For example, cowpea varieties with
hard seeds can be a weed problem in soybean crops. The hard cowpea
seeds over-winter in the soil and can produce plants in subsequent
years; these cowpea plants often can't be easily killed by soybean
herbicides (closely related plant) and the seeds are often so close in
size to soybean seeds that [they] can be difficult to remove from the
harvested soybean product'' (Ref. 42). However, EPA considers that the
key consideration is the plant's behavior in natural settings,
including semi-managed habitat surrounding agricultural fields, as
opposed to its behavior within the fields themselves. Third, these
experts agreed that it is unlikely that acquisition of virus resistance
would make cowpea weedy or invasive. For example, one expert stated ``I
am not aware of any virus problem in cowpea, if resolved via transgenic
means, would result in the crop becoming feral'' (Ref. 42). EPA
therefore believes that cowpea meets the conditions recommended by the
2005 SAP for inclusion on the list and will present low risk with
respect to weediness.
n. Cucumber. EPA proposes that cucumber (Cucumis sativus) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with cucumber experts. These consultations indicate that cucumber meets
the three conditions outlined above by the SAP: It does not have wild
or weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make cucumber weedy or invasive. The experts contacted
by EPA indicated agreement with these statements. For example, one
expert stated that ``cucumber could not become feral due to acquired
transgenic virus resistance. The failure for [cucumber] to survive
without human intervention is not due to disease attack, but rather due
to [its] ability to compete with native plants and weeds, and to
withstand the stresses they are exposed to outside of cultivation,
particularly drought'' (Ref. 42). EPA therefore believes that cucumber
meets the conditions recommended by the 2005 SAP for inclusion on the
list and will present low risk with respect to weediness.
o. Gerbera. EPA proposes that gerbera (Gerbera spp.) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with gerbera
experts. Two experts indicated that there are no wild or weedy
relatives in the United States with which gerbera can form viable
hybrids in nature. A third said, ``Gerbera jamesonii Bolus ex Adlam has
been recorded as naturalized in Florida. However, it is most likely
Gerbera hybrida (Gerbera jamesonii x G. viridiflora Schultz-Bip) which
is the designation for the commercially available Gerberas'' (Ref. 42).
Regarding the ferality of gerbera species, two experts believed feral
populations were not known to occur, while a third noted, ``Although G.
jamesonii (or G. hybrida) is attributed to Florida, it is most likely a
low risk for forming feral populations'' (Ref. 42). All three experts
believed it unlikely that acquired virus resistance could lead to
gerbera becoming feral or easily spreading into non-crop areas. One
expert said, ``Gerbera, in general, is a short-lived perennial in the
United States. It suffers from a number of fungal and bacteria
pathogens. A transgenic virus-resistant Gerbera offers little in terms
of [increased] fitness and increased invasive potential'' (Ref. 42).
p. Gladiolus. EPA proposes that gladiolus (Gladiolus spp.) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with gladiolus experts. These consultations indicate that gladiolus
meets the three conditions outlined above by the SAP: It does not have
wild or weedy relatives in the United States with which it can form
viable hybrids in nature, it is not currently weedy or invasive in the
United States, and there is no reason to believe that acquisition of
virus resistance would make gladiolus weedy or invasive. The experts
contacted by EPA indicated agreement with these statements. For
example, one expert said, ``No gladiolus species or hybrid has ever
been documented as having successfully naturalized in the United
[[Page 19605]]
States. Virus resistance is not likely to make this any more likely''
(Ref. 42). EPA therefore believes that gladiolus meets the conditions
recommended by the 2005 SAP for inclusion on the list and will present
low risk with respect to weediness.
q. Lentil. EPA proposes that lentil (Lens culinaris) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with lentil
experts. Although lentil was not on the list of plants recommended by
the 2004 SAP, several experts consulted about other crops mentioned
that lentil also appeared to meet the criteria that EPA was
investigating. Consultations about lentil indicate that it meets the
three conditions outlined above by the SAP: It does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make lentil weedy or invasive. The experts contacted
by EPA indicated agreement with these statements. For example, one
expert stated, ``Lentil could not possibly survive in the wild on its
own. [Lentils are] rather delicate plants, small in stature and very
weak in competition for space or water. It needs great care from grower
[sic] to produce seeds in cultivation. Its seed could not possibly
survive in the wild due to rotting by soil-born microorganisms.
Resistance to one or more viruses will not increase the survivability
of lentil seeds in the wild'' (Ref. 42). EPA therefore believes that
lentil meets the conditions recommended by the 2005 SAP for inclusion
on the list and will present low risk with respect to weediness.
r. Mango. EPA proposes that mango (Mangifera indica) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with mango
experts. These consultations indicate that mango meets the three
conditions outlined above by the SAP: It does not have wild or weedy
relatives in the United States with which it can form viable hybrids in
nature, it is not currently weedy or invasive in the United States, and
there is no reason to believe that acquisition of virus resistance
would make mango weedy or invasive. All three experts contacted by EPA
indicated agreement with these statements. For example, one expert
stated, ``spread of mango seed by humans or animals into non-crop areas
is rare and suitable environments are few. Transgenic resistance should
not affect the likelihood of spread. Viral susceptibility is not an
important factor limiting the plant's ability to become feral'' (Ref.
42). EPA therefore believes that mango meets the conditions recommended
by the 2005 SAP for inclusion on the list and will present low risk
with respect to weediness.
s. Orchids. EPA proposes that all genera of orchids in the family
Orchidaceae be included on the list in Sec. 174.27(a)(1) based on EPA
consultations with orchid experts. These consultations indicate that
orchids meet the three conditions outlined above by the SAP: They do
not have wild or weedy relatives in the United States with which they
can form viable hybrids in nature, they are not currently weedy or
invasive in the United States, and there is no reason to believe that
acquisition of virus resistance would make orchids weedy or invasive.
All three experts contacted by EPA indicated agreement with these
statements. For example, one expert stated, ``Species within these
genera have specific insect pollinators and those insects are unlikely
[to] be present for pollination in United States. In addition, species
within these genera are very difficult to grow from seed without human
intervention, requiring a symbiotic relationship with a specific fungal
species. Acquiring transgenic resistance to one or more viruses would
not affect pollination or seed germination'' (Ref. 42). EPA therefore
believes that species in the orchid family meet the conditions
recommended by the 2005 SAP for inclusion on the list and will present
low risk with respect to weediness.
t. Papaya. EPA proposes that papaya (Carica papaya) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with papaya
experts. These consultations indicate that papaya meets the three
conditions outlined above by the SAP. First, it does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature. Although Carica papaya has been successfully crossed
with Vasconellea species using laboratory-based embryo rescue
techniques, such hybrids do not form in nature (Ref. 42). Second,
although all three breeding experts agreed that papaya is known to
establish outside of agricultural areas through human- and animal-
mediated seed dispersal, the species is not considered to be weedy or
invasive. For example, one expert stated, ``I have observed small feral
[papaya] populations in Guam, Hawaii and Puerto Rico... in areas close
to human dwellings and activities.... The feral papayas are not weedy
and are nonaggressive, they can easily be removed by cutting down.''
Further, as stated in USDA-APHIS' response to a petition for
determination of nonregulated status for transgenic virus-resistant
papaya, ``Papaya is not listed as a weed in the Federal Noxious Weed
Act (7 U.S.C. 2801-2813) and is not reported by the Weed Society of
America to be a common or troublesome weed anywhere in the United
States (Bridges and Bauman, 1992; Holm et al. 1979; Muenscher, 1980)''
(Ref. 46). Third, two of three experts indicate there is no reason to
believe that acquisition of virus resistance would make papaya weedy or
invasive. The third expert said that it was ``[v]ery likely'' papaya
would become feral or easily spread into non-crop areas if it acquired
transgenic resistance to one or more viruses because ``[a]necdotal and
informal reports at papaya conferences gave evidence that the virus
resistance transgene was found in feral populations'' (Ref. 42).
However, this comment seems to reflect the fact, as noted above, that
papaya does occasionally form feral populations in spite of not being
weedy or aggressive, and this characteristic would be expected whether
the papaya is transgenic or not. In his comments to EPA, another expert
concludes by saying that territorial records show papaya was not a weed
in Hawaii prior to the discovery of papaya viruses in the 1940s. If
papaya was not considered a weed prior to exposure to viruses, then
there is no reason to believe that a virus resistant papaya would
become a weed. Another expert corroborates this conclusion by stating,
``I see no competitive advantage of [virus-resistant] transgenic
papayas over nontransgenic papayas.... Papaya requires high levels of
human inputs to thrive or survive, including fertilizers, chemicals and
care'' (Ref. 42). EPA therefore believes that papaya meets the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
u. Pea. EPA proposes that pea (Pisum sativum) be included on the
list in Sec. 174.27(a)(1) based on EPA consultations with pea experts.
These consultations indicate that pea meets the three conditions
outlined above by the SAP: It does not have wild or weedy relatives in
the United States with which it can form viable hybrids in nature, it
is not currently weedy or invasive in the United States, and there is
no reason to believe that acquisition of virus resistance would make
pea weedy or invasive. All three experts contacted by EPA indicated
agreement with these statements. For example, one expert stated, ``pea
is not likely to become feral or easily spread into non-
[[Page 19606]]
crop areas due to acquired resistance to one or more viruses.
Acquisition of transgenic viral resistance would not provide any
adaptive advantage for survival of the transgenic crop plants. Peas
have been produced in the US for more than 75 years with infrequent
viral epidemics (5-9 year cycles) and no feral populations of pea have
been recorded; therefore environmental and cultural conditions are the
more likely agent preventing establishment of feral populations'' (Ref.
42). EPA therefore believes that pea meets the conditions recommended
by the 2005 SAP for inclusion on the list and will present low risk
with respect to weediness.
v. Peanut. EPA proposes that peanut (Arachis hypogaea) be included
on the list in Sec. 174.27(a)(1) based on EPA consultations with
peanut experts. These consultations indicate that peanut meets the
three conditions outlined above by the SAP: It does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make peanut weedy or invasive. All three experts
contacted by EPA indicated agreement with these statements. For
example, one expert stated, ``virus pressure is not the limiting
factor. Even without virus pressure peanut (Arachis hypogaea) are not
able to become feral or easily spread into non-crop areas. Peanut are
not able to sustain long term natural populations without cultivation
by man'' (Ref. 42). EPA therefore believes that peanut meets the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
w. Pineapple. EPA proposes that pineapple (Ananas comosus) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with pineapple experts. These consultations indicate that pineapple
meets the three conditions outlined above by the SAP. One, it does not
have wild or weedy relatives in the United States with which it can
form viable hybrids in nature. One expert indicated, ``The taxonomy of
the genus Ananas was recently critically reviewed and revised (Chan et
al., 2003) and all of the wild relatives of pineapple are classified in
the same genus and species as the cultivated pineapple but are
different botanical varieties. These are Ananas comosus var.
ananassoides and A. comosus var. parguazensis (Chan et al., 2003). If
these wild relatives are found in the United States and its territories
they would be in cultivated gardens or in pots. There are no reports
that A. comosus var comosus or its wild relatives survive naturally in
the wild or pose a potential threat as weed species. If natural crosses
between Ananas species occur in nature, it is highly unlikely that seed
produced from them would survive to produce a mature plant'' (Refs. 42
and 47). Second, the experts agreed that pineapple is not currently
weedy or invasive in the United States. Third, these experts agreed
that it is unlikely that acquisition of virus resistance would make
pineapple weedy or invasive. For example, one expert stated, ``Assuming
transgenic plants were resistant to all known pests, pineapple still
cannot compete with weeds, which quickly overtop slower growing
pineapple plants. Pineapple lacks any natural mechanism for vegetative
propagation and does not propagate naturally by seeds because seedlings
are delicate and require special care to survive to maturity'' (Ref.
42). EPA therefore believes that pineapple meets the conditions
recommended by the 2005 SAP for inclusion on the list and will present
low risk with respect to weediness.
x. Potato. EPA proposes that potato (Solanum tuberosum) be included
on the list in Sec. 174.27(a)(1) based on the Agency's experience
regulating PIPs in potato (Ref. 44), literature that is available on
potato biology, the OECD Consensus Document on the Biology of Solanum
tuberosum subsp. tuberosum (Potato) (Ref. 48), and EPA consultations
with potato experts (Ref. 42). This body of information indicates that
potato is low risk with respect to concerns associated with weediness.
EPA's 2001 risk assessment for Bt PIPs evaluated the potential for
potato to form viable hybrids with wild or weedy relatives in the
United States (Ref. 44). EPA's conclusion was that there is no
foreseeable risk of gene capture and PIP expression in wild relatives
of Solanum tuberosum in the United States. Successful gene
introgression into tuber-bearing Solanum species is virtually excluded
due to constraints of geographical isolation and other biological
barriers to natural hybridization (Ref. 49). These barriers include
incompatible (unequal) endosperm balance numbers that lead to endosperm
failure and embryo abortion, multiple ploidy levels, and
incompatibility mechanisms that do not express reciprocal genes to
allow fertilization to proceed. No natural hybrids have been observed
between these species and cultivated potatoes in the United States.
The body of information EPA consulted on potato also indicates that
the crop is not currently weedy or invasive in the United States.
According to the OECD consensus document, ``[o]utside the field, potato
seedlings will have difficulty establishing themselves as they cannot
compete with other plants. Love et al., 1994 report that these
seedlings are limited to cultivated areas for reasons of competition
and adaptation. Potato tubers can be spread during transportation and
use, but generally these plants will not be established for a long time
due to unfavourable environmental conditions. In general, the potato is
not known as a coloniser of unmanaged ecosystems'' (Ref. 48). One
expert EPA consulted indicated potato ``is a rare weed in potato plots
but it never becomes feral in the United States'' (Ref. 42).
Finally, there is no reason to believe that acquisition of virus
resistance would make potato weedy or invasive, as viruses are not
consistently associated with failure of potato to show any evidence of
being weedy or invasive. The experts that EPA consulted agree that it
is not very likely that potato would become feral or easily spread into
non-crop areas if it acquired transgenic virus resistance. For example,
one expert consulted indicated that ``[t]he basis of poor survival of
cultivars in natural habitats is not due to virus susceptibility''
(Ref. 42). EPA therefore believes that potato meets the conditions
recommended by the 2005 SAP for inclusion on the list and will present
low risk with respect to weediness.
y. Soybean. EPA proposes that soybean (Glycine max) be included on
the list in Sec. 174.27(a)(1) based on literature that is available on
soybean biology, the OECD Consensus Document on the Biology of Glycine
max (L.) Merr. (Soybean) (Ref. 50), and EPA consultations with soybean
experts. This body of information indicates that soybean meets the
three conditions outlined above by the SAP: It does not have wild or
weedy relatives in the United States with which it can form viable
hybrids in nature, it is not currently weedy or invasive in the United
States, and there is no reason to believe that acquisition of virus
resistance would make soybean weedy or invasive, as viruses are not
consistently associated with failure of soybean to show any evidence of
being weedy or invasive. All four experts contacted by EPA indicated
agreement with these statements. For example, one expert stated,
``Acquiring transgenic virus resistance will not change the ability of
soybean to become feral since it will still be a domesticated species
and does not have the attributes to
[[Page 19607]]
survive without human intervention. Virus diseases in the U.S. do not
generally cause major yield loses [sic] and resistance to some viruses
is very common in soybean. Transgenic virus resistance will not
substantially change how the soybean interacts with most environments''
(Ref. 42). According to the OECD consensus document, ``[t]he soybean
plant is not weedy in character. In North America, Glycine max is not
found outside of cultivation. In managed ecosystems, soybean does not
effectively compete with other cultivated plants or primary
colonizers'' (Ref. 50). EPA therefore believes that soybean meets the
conditions recommended by the 2005 SAP for inclusion on the list and
will present low risk with respect to weediness.
z. Starfruit. EPA proposes that starfruit (Averrhoa carambola) be
included on the list in Sec. 174.27(a)(1) based on EPA consultations
with starfruit experts. These consultations indicate that starfruit
meets the three conditions outlined above by the SAP. One, it does not
have wild or weedy relatives in the United States with which it can
form viable hybrids in nature. One expert mentioned that starfruit can
hybridize with wild Averrhoa carambola, but another expert indicated
that researchers have concluded wild starfruit trees can no longer be
found in the United States (Ref. 42). Second, these experts agreed that
starfruit is not currently weedy or invasive in the United States.
Third, these experts agreed that it is unlikely that acquisition of
virus resistance would make starfruit weedy or invasive. For example,
one expert stated, ``It is highly unlikely that starfruit with acquired
transgenic resistance would spread to non-crop areas because... seed
recalcitrance in starfruit... results in a loss of viability shortly
after harvest'' (Ref. 42). EPA therefore believes that starfruit meets
the conditions recommended by the 2005 SAP for inclusion on the list
and will present low risk with respect to weediness.
aa. Sugarcane. EPA proposes that sugarcane (Saccharum officinarum)
be included on the list in Sec. 174.27(a)(1) based on EPA
consultations with sugarcane experts. These consultations indicate that
sugarcane meets the three conditions outlined above by the SAP. One, it
does not have wild or weedy relatives in the United States with which
it can form viable hybrids in nature. According to one expert,
``Although in theory it should happen in more tropical regions of the
world, hybrid seedlings among commercial or wild relatives are not
observed. Breeders routinely generate hybrids among commercial
sugarcane (derived from interspecific hybrids of Saccarhum [sic]
officinarum and S. sponteneum), and among commercial and wild relatives
(S. spontaneum mostly) under controlled conditions of heating and
photoperiod control. The resulting progeny are quite weak and must be
husbanded under greenhouse-type conditions prior to planting in the
field'' (Ref. 42). Second, these experts agreed that sugarcane is not
currently weedy or invasive in the United States. One expert stated,
``Commercial sugarcane is clonally propagated. Occasionally some of the
harvested cane may be lost from the trucks or wagons while in transport
from the field to the processing factory. If the cane has not been
burned prior to harvest, volunteer plants occasionally grow along the
transport route. This cane is not sexually reproducing, nor is it
invasive in nature. Simple roadside mowing or natural weather
conditions usually eliminate it'' (Ref. 42). Third, these experts
agreed that it is unlikely that acquisition of virus resistance would
make sugarcane weedy or invasive. For example, one expert stated,
``commercial sugar does not become a feral pest under regular
commercial production conditions. The majority of existing commercial
cultivars have been bred for genetic resistance to various disease-
causing sugarcane viruses. None of these cultivars have become feral or
a pest in anyway [sic]'' (Ref. 42). EPA therefore believes that
sugarcane meets the conditions recommended by the 2005 SAP for
inclusion on the list and will present low risk with respect to
weediness.
bb. Tulips. EPA proposes that tulips (Tulipa spp.) be included on
the list in Sec. 174.27(a)(1) based on EPA consultations with tulip
experts. These consultations indicate that tulips meet the three
conditions outlined above by the SAP. One, they do not have wild or
weedy relatives in the United States with which they can form viable
hybrids in nature. Two, they are not currently weedy or invasive in the
United States, although two experts indicated that Tulipa sylvestris
naturalizes in certain areas without being viewed as a significant
problem because it reproduces only vegetatively. Three, there is no
reason to believe that acquisition of virus resistance would make
tulips weedy or invasive. One expert noted that this was ``possible,
but unlikely. Virus resistance could conceivably increase the vigor of
the vegetative spread of T. sylvestris'' (Ref. 42). However, three
other experts believed that this was highly unlikely to occur. One
said, ``The need for chilling in this genus means that it is restricted
to temperate areas with summer-cool climates. Areas where it can
persist are very limited and there is a high degree of browsing of this
genus by vertebrates such as deer that make seed production in the wild
a very rare occurrence in nature in the U.S.'' (Ref. 42). EPA therefore
believes that tulips meet the conditions recommended by the 2005 SAP
for inclusion on the list and will present low risk with respect to
weediness.
ii. Adding plants to the categorical exemption criterion in Sec.
174.27(a)(1). As the Agency gains additional experience, it may propose
to add crops to the list. In addition, any person may petition the
Agency to add particular crops to the list. EPA would evaluate any
potential candidates against the same considerations used in this
rulemaking to develop the list in Sec. 174.27(a)(1) discussed above.
Consequently, for a petition to be successful, it should contain
sufficient data or other information to allow EPA to perform such an
analysis, e.g., published information or a consensus opinion among
experts in the particular crop that addresses the questions EPA posed
in its expert consultations (discussed in Unit III.C.2.i.). Petitioners
are welcome to consult with EPA prior to preparing a submission to
discuss the information that would be required. EPA would consult with
USDA in evaluating petitions for adding plants to Sec. 174.27(a)(1).
Any subsequent addition of crops to the list in Sec. 174.27(a)(1),
either through the Agency's own initiative or in response to a petition
from the public, may only occur through rulemaking. Under FIFRA section
25, rulemaking involves several steps, including reviews by the SAP and
USDA. In general, EPA would seek to expedite the process and proceed
through direct final rulemaking where feasible. Under such a process,
in cases where EPA believes that the proposal will not raise
scientifically complicated issues, EPA would simultaneously issue a
final rule and a proposal. If no adverse comments were received, the
final rule would go into effect and EPA would withdraw the proposed
rule. In the event of adverse comment, EPA would withdraw the final
rule and would proceed to issue a final rule that addressed the public
comments received on the proposal. In addition, as part of this current
rulemaking, because EPA's analysis to determine whether to add a crop
to the list would be consistent with the criteria provided by the SAP,
the Agency would request that the SAP generally waive its
[[Page 19608]]
review of subsequent rules seeking to add further crops to the list in
Sec. 174.27(a)(1) unless EPA subsequently determines that a particular
rule raised novel or particularly complex scientific issues.
iii. Proposed exemption criterion conditional on Agency
determination in Sec. 174.27(a)(2). EPA recognizes that many PVCP-PIP/
plant combinations would reasonably be expected to pose low risk with
respect to weediness even though the crop plant containing the PVCP-PIP
is not on the Agency's proposed list in Sec. 174.27(a)(1). EPA has not
conducted an exhaustive survey of all crop plants to evaluate them for
inclusion on this list and therefore recognizes that additional plants
may meet the conditions that were used to compile this list of plants.
Therefore, in addition to the categorical exemption criterion, EPA also
believes that a criterion conditional on Agency determination could be
developed that would identify plants that are low risk with respect to
weediness.
EPA is considering four options for such a conditional exemption
criterion under which PVCP-PIP/plant combinations that fail to meet
Sec. 174.27(a)(1) could still meet Sec. 174.27(a) under Sec.
174.27(a)(2), subject to an Agency review. Each of the options reflects
a somewhat different approach to implementing the recommendations of
the 2005 SAP (Ref. 11). EPA does not currently have a preferred
approach and presents several options to promote full consideration of
the issues, although option 1 is presented in the regulatory text so
the public could see how Sec. 174.27(a)(2) might fit into the overall
framework of the exemption.
a. Option 1. The first option for Sec. 174.27(a)(2) provides the
strictest interpretation of the 2005 SAP advice. Under this option, a
PVCP-PIP would meet Sec. 174.27(a) under Sec. 174.27(a)(2) if the
Agency determines after review that the plant containing the PIP meets
all of the following:
(i) Has no wild or weedy relatives in the United States with
which it can form viable hybrids in nature.
(ii) Is not a weedy or invasive species outside of agricultural
fields in the United States.
(iii) Is unlikely to establish weedy or invasive populations
outside of agricultural fields in the United States even if the
plant contains a PVCP-PIP.
EPA would expect exemption submissions to document that the plant
meets these conditions in the opinion of agronomists, breeders,
ecologists, and other experts working with the specific taxa in
question or based on data. When these conditions are met, the
likelihood that a PVCP-PIP could cause increased weediness of any plant
would be very small, as discussed in the following paragraphs.
If the plant containing the PVCP-PIP has no wild or weedy relatives
in the United States with which it can form viable hybrids in nature
and thus would meet the criterion in Sec. 174.27(a)(2)(i) under option
1, it would not be possible for the PVCP-PIP to inadvertently be
transferred to any wild or weedy relatives, e.g., through pollen flow.
Whether the recipient plant ``can produce viable hybrids in nature'' is
a critical attribute that would definitively determine the potential
for introgression of the PVCP-PIP into a native or naturalized plant
population. Although hybrids must be able to reproduce themselves in
order for introgression to occur, the production of ``viable'' hybrids
(i.e., those that are able to grow) may be described more clearly in a
regulatory standard than examining the reproductive potential of any
hybrids. In many cases, reproductive potential of hybrids has not been
fully investigated. Given that reduced fertility in F1 crop-wild
hybrids is frequently restored to normal in subsequent generations
(Ref. 37), measurement of hybrid fertility involves consideration of
several generations. In addition, viability is a more reliable standard
because even very low rates of gene transfer could lead to
introgression (Ref. 51), suggesting that any degree of hybrid fertility
could indicate the potential for introgression to occur. As noted by
the 2005 SAP, ``it is known that favorable alleles (including, perhaps,
a PVCP-PIP) can pass easily from one species to another through hybrid
zones, even when the hybrids have very low fitness (Barton 1986)''
(Refs. 11 and 52). The Agency recognizes that introgression of a trait
such as virus resistance into natural plant populations does not
automatically confer a competitive advantage to the recipient
population. However, at this time, there is little information
available to predict categorically whether acquisition of such a trait
might affect the competitiveness of a specific plant population, and
the available information does not allow the Agency to make this
determination a priori. The ability to produce viable hybrids is
relatively easy to evaluate, resulting in a clear criterion that
ensures an effective limitation on the potential for introgression.
Such language also clarifies that the relevant question is whether the
hybrid can be produced ``in nature.'' The fact that plants could be
crossed in the laboratory or greenhouse is not necessarily indicative
of a plant's true reproductive potential. The Agency's focus is whether
a viable hybrid could be produced under normal growing conditions in
the field or in nature, rather than under controlled experimental
conditions that might have little relevance to behavior in the
environment.
If the plant containing the PVCP-PIP is not a weedy or invasive
species outside of agricultural fields in the United States and thus
would meet the criterion in Sec. 174.27(a)(2)(ii) under option 1,
established and persistent feral populations of the crop presenting
difficult management issues in natural or semi-managed ecosystems would
be unlikely. Thus, transfer of the PVCP-PIP from the crop to a feral
population would be unlikely to exacerbate what could already be a
difficult problem by inadvertently increasing the population's
weediness potential. EPA proposes inclusion of the term ``outside of
agricultural fields'' to emphasize that the key consideration is the
plant's behavior in natural settings, including semi-managed habitat
surrounding agricultural fields as opposed to its behavior within the
fields themselves. EPA recognizes that most crops within agricultural
fields form volunteer populations, where propagules of the crop from
the previous rotation grow in the subsequent crop rotation. The Agency
believes the language ``outside of agricultural fields'' appropriately
excludes this situation from consideration.
If the plant containing the PVCP-PIP is unlikely to establish weedy
or invasive populations outside of agricultural fields in the United
States even if the plant contains a PVCP-PIP and thus would meet the
criterion in Sec. 174.27(a)(2)(iii) under option 1, an additional
level of assurance would be provided that the crop plant would not
present weediness concerns through acquisition of a PVCP-PIP. EPA
believes that this condition could in general be met based on the
opinion of experts on the particular crop. Experts may judge, for
example, that acquisition of virus resistance is unlikely to change the
weedy or invasive characteristics of the plant if the crop does not
appear to be weedy or invasive when virus infection is known to be
absent from a particular area or over a particular period of time.
Available empirical data could be used in the determination or may be
gathered if expert opinion cannot resolve the question.
EPA proposes to define the term ``weedy species'' used in Sec.
174.27(a)(2)(ii) to mean ``a species that
[[Page 19609]]
is an aggressive competitor in natural ecosystems.'' EPA intends to use
the term ``invasive species'' consistent with the definition in
Executive Order 13112, meaning an alien species whose introduction
causes or is likely to cause economic or environmental harm or harm to
human health. An alien species means, with respect to a particular
ecosystem, any species, including its seeds, eggs, spores, or other
biological material capable of propagating that species, that is not
native to that ecosystem. EPA uses the phrase ``weedy or invasive
populations'' in Sec. 174.27(a)(2)(iii) consistent with these
definitions.
EPA notes that the criterion in Sec. 174.27(a)(2)(i) under option
1 does not necessarily strictly hold for every crop that appears on the
list in proposed Sec. 174.27(a)(1). In some cases, EPA was able to
make a low risk determination for a particular crop, e.g., corn, in
spite of the possible presence of wild or weedy relatives in the United
States with which the plant may in rare cases form viable hybrids in
nature. EPA has presented the basis for such conclusions in this
proposed rule, and the public can clearly understand why the crops in
Sec. 174.27(a)(1) meet the Agency's low risk standard with respect to
weediness concerns. Given that several crops for which EPA has made a
low risk determination and proposes to include in Sec. 174.27(a)(1)
would not meet Sec. 174.27(a)(2) as proposed under option 1, EPA
believes that option 1 may be too narrow. Accordingly, EPA is
considering other options for Sec. 174.27(a)(2) that are based on a
less literal interpretation of the SAP's recommendations but which the
Agency believes are nevertheless consistent with the SAP's intent.
b. Option 2. The second option EPA is considering is that a PVCP-
PIP would meet the criterion in Sec. 174.27(a)(2)(i) if ``the plant
containing the PIP has no wild or weedy relatives in the United States
with which it can form viable, fertile hybrids in nature, or if
fertile, the resulting hybrid cannot establish populations in the
environment.'' EPA is considering this option because most crops are
able to form viable hybrids with a wild or weedy relative in some part
of the United States. However, some viable, fertile hybrids may
nevertheless present low risk with respect to concerns associated with
weediness, e.g., if the hybrids are weak and lack the ability to
establish. On the other hand, fertility and the potential to establish
are more difficult characteristics to evaluate than viability because
many more variables affect the determination, suggesting that it might
be more appropriate in these cases for the Agency to require that data
be collected for a period of time after commercial deployment that
could confirm the Agency's original analysis. However, while such
conditions may be readily placed on a PVCP-PIP registration, they could
not be placed on an exempt PVCP-PIP. In addition, determinations under
option 2 would be more difficult for the public to predict than
determinations under option 1, as discussed in Unit III.A.2.
c. Option 3. Under the third option being considered, EPA would
adopt only the criteria in Sec. 174.27(a)(2)(i) and (a)(2)(ii) as
discussed above under option 1. The rationale for such an approach is
that it may not be necessary to evaluate the criterion in Sec.
174.27(a)(2)(iii) in order to make a low risk determination because the
issues are adequately addressed by the other two criteria. Viruses
generally do not uniformly affect crops every season in every place
they are planted - even those crops that viruses significantly impact
such that development of a PVCP-PIP to combat the disease might be
undertaken. Crops will thus have repeated opportunity to escape
cultivation in seasons and in areas where there is no virus
infestation. If weedy tendencies are rarely or never observed in any
part of the crop's range, it is unlikely that virus resistance affects
the crop's ability to escape cultivation and establish weedy
populations. Unlike wild or weedy plant relatives that may at times be
infected by viruses and may be negatively impacted by viruses in ways
that are not obvious to untrained observers, breeders and farmers are
intimately aware of the type of damage done by virus infection to crops
and are therefore well aware when their fields are or are not infected.
Crop plants have been observed under a diverse range of environmental
conditions over many years. If a PVCP-PIP were likely to make a crop
weedy or invasive, such tendencies would likely have been observed even
without virus resistance at some point in time given the level of
observation crops generally receive due to the necessity to actively
manage their cultivation. Such crops showing weedy or invasive
tendencies would not meet the criterion in Sec. 174.27(a)(2)(ii),
suggesting that the criterion in Sec. 174.27(a)(2)(iii) is largely
redundant with this condition.
EPA notes that option 3 is likely to be equally as narrow as
options 1 and 2. The advantage of the option would be a simplification
of the issues that a PVCP-PIP developer would need to address as part
of a submission for an exemption determination.
EPA could consider factors that are not considered under options 1-
3 but that would affect the potential impact of PVCP-PIP acquisition as
part of evaluating a PVCP-PIP for FIFRA registration. For example, EPA
could take into account the effect of virus infection on such species,
the existence and impact of any natural virus resistance in the
population, the overlap of the plant's distribution with crop
cultivation areas, and other relevant considerations.
d. Option 4. The fourth option EPA is considering is that a PVCP-
PIP would meet Sec. 174.27(a)(2) if the Agency determines that ``the
PVCP-PIP is unlikely to significantly change the population size or
distribution of the species containing the PVCP-PIP outside of
agricultural fields or the population size or distribution of any wild
or weedy species in the United States that could acquire the PVCP-PIP
through gene transfer.'' EPA is considering this fourth option because
the Agency recognizes that many PVCP-PIPs excluded from exemption under
the criterion in Sec. 174.27(a)(2)(i) of options 1-3 because of wild
or weedy relatives in the United States may nevertheless present low
risk. The presence of wild or weedy relatives relates only to potential
exposure of the PVCP-PIP and does not indicate whether the PVCP-PIP is
likely to cause any adverse effects even if it were to transfer to
these relatives. EPA believes that such an evaluation would be
consistent with the advice of the 2005 SAP, which noted that ``[t]he
probability that a particular transgene will lead to increased
weediness depends on the phenotype conferred by the transgene and on
the ecological factor(s) currently limiting the size or distribution of
the wild species. In particular, if the transgene alters plant response
to an ecological factor limiting population size, then population
dynamics may be affected. For PVCP-PIPs, the relevant consideration is
whether virus resistance (conferred by the PVCP-PIP) leads to changes
in the size or distribution of wild plant species with the PVCP-PIP''
(Ref. 11).
With option 4, EPA would conduct a risk assessment to evaluate a
clear end point - whether there is likely to be a significant change in
the population size or distribution of the species containing the PVCP-
PIP outside of agricultural fields or the population size or
distribution of any wild or weedy species in the United States that
could acquire the PVCP-PIP through gene transfer. However, for the vast
majority of species, many characteristics that would influence this
determination are
[[Page 19610]]
currently poorly understood, e.g., the impact of virus infection on
wild plant populations and the likely selective advantage afforded by
acquisition of virus resistance. As a result, both the nature of EPA's
evaluation and the type and extent of data that might need to be
provided to the Agency resemble much more closely what would be
required to evaluate weediness issues during a FIFRA registration
review. In addition, the more the exemption determination process
resembles a full risk assessment, the longer the time required for EPA
to complete such a review.
Although EPA would seek public comment on determinations that a
PVCP-PIP met Sec. 174.27(a)(2) according to the procedure for
exemptions utilizing any Agency-determined criteria, Agency
determinations may be more controversial with this option than with
other options that have more clearly defined criteria. EPA believes
that case-by-case determinations could be made appropriately and that
the data requirements needed to evaluate the criterion under option 4
would not necessarily be overly burdensome. EPA notes that in many
cases much of the data, if not all, needed for EPA to evaluate a
criterion such as this fourth option would also be needed for a
petition for determination of nonregulated status submitted to USDA.
EPA believes that the flexibility of this option will make it more
likely that the Agency would identify the largest number of low risk
products that could qualify for exemption.
For all options for proposed Sec. 174.27(a)(2), the Agency
believes the entire United States is the relevant scope of inquiry
because the proposed exemption would carry no limitations on where the
exempted PVCP-PIP/plant combination could be planted and thus could be
planted in all areas subject to U.S. law. FIFRA section 2(aa) defines
``State'' as ``a State, the District of Columbia, the Commonwealth of
Puerto Rico, the Virgin Islands, Guam, the Trust Territory of the
Pacific Islands, and American Samoa. Accordingly, the term ``United
States'' used in this proposal includes all these areas, and EPA
proposes to incorporate a definition of ``United States'' paralleling
the FIFRA definition of ``State'' into the definitions in 40 CFR 174.3.
As an alternative to Agency review pursuant to Sec. 174.27(a)(2),
a developer could petition EPA to add a crop to the list in Sec.
174.27(a)(1). In some cases, EPA expects that the same data/information
that would support a determination that a crop meets Sec. 174.27(a)(2)
would support listing the crop in Sec. 174.27(a)(1). However, because
a plant can only be added to the list in Sec. 174.27(a)(1) through
rulemaking, EPA expects that many developers will instead prefer to
obtain an Agency determination under Sec. 174.27(a)(2). However, once
a plant is added to the list in Sec. 174.27(a)(1), future PVCP-PIPs
used in that plant would meet Sec. 174.27(a) without any Agency
review.
3. Historical approaches. In 1994 EPA proposed two different
alternatives for exempting PVCP-PIPs from FIFRA requirements. The
Agency prefers the approaches discussed in the preceding Subunit
because they have been developed based on recent interactions with the
SAP and thus represent the most current science. One 1994 alternative
contained exemption criteria directed towards addressing concerns
associated with gene transfer to identify those PVCP-PIP/plant
combinations with the lowest potential to confer selective advantage on
wild or weedy plant relatives. EPA described this alternative exemption
as follows:
Coat proteins from plant viruses [would be exempt] if the
genetic material necessary to produce a coat protein is introduced
into a plant's genome and the plant has at least one of the
following characteristics:
(1) The plant has no wild relatives in the United States with
which it can successfully exchange genetic material, i.e., corn,
tomato, potato, soybean, or any other plant species that EPA has
determined has no sexually compatible wild relatives in the United
States.
(2) It has been demonstrated to EPA that the plant is incapable
of successful genetic exchange with any existing wild relatives
(e.g., through male sterility, self-pollination).
(3) If the plant can successfully exchange genetic material with
wild relatives, it has been empirically demonstrated to EPA that
existing wild relatives are resistant or tolerant to the virus from
which the coat protein is derived or that no selective pressure is
exerted by the virus in natural populations (59 FR 60504, November
23, 1994).
EPA carefully reconsidered this 1994 proposal in its deliberations
for today's proposed exemption and presented these criteria in modified
form to the FIFRA SAP at the October 2004 and December 2005 meetings
for consideration. In light of comments received from the FIFRA SAP and
additional scientific information available since 1994, EPA no longer
believes this alternative would adequately address questions associated
with weediness in a manner that could be reasonably implemented.
However, EPA still considers that it would be appropriate to limit the
exemption based on the concerns outlined in the earlier proposal
associated with acquisition of virus resistance through hybridization
with a transgenic plant containing a PVCP-PIP.
Although similar in intent to characteristic (1) of this option
proposed in 1994, today's proposed criterion in Sec. 174.27(a)(2)(i)
under option 1 focuses in part on the potential to ``form viable
hybrids in nature'' rather than simply ``exchange genetic material''
because the former is a clearer standard for determining whether a
PVCP-PIP could have the potential to affect a recipient plant
population negatively. The ability to exchange genetic material, which
is often demonstrated by performing hand crosses in the laboratory or
greenhouse, may not indicate any relevant information about how the
plants would behave in nature. Today's proposed criterion in Sec.
174.27(a)(1) also uses a somewhat different list of plants than the
four in the 1994 proposal. Several species have been added (see Unit
III.C.2.i.) and tomato has been removed from the list because of
information acquired through expert consultation. (See Unit VII for a
discussion of this information and to read EPA's request for comment).
When EPA presented a criterion similar to the first characteristic in
the 1994 proposal to the 2004 SAP, they responded that ``the Panel was
of the opinion that the absence of a competent wild/weedy relative
positioned in relation to the plant containing the PVCP-PIP was an
appropriate condition.'' The 2005 SAP also ``was supportive of the
Agency's intent to exempt from regulation any PVCP-PIP crops that (1)
do not have sexually compatible wild relatives in the location of
intended cultivation (US & Territories) and (2) are not likely to
become weedy themselves'' (Ref. 11).
EPA now also believes that characteristic (2) of the option
proposed in 1994 may be insufficient based on the conclusions of the
2004 SAP and the National Research Council that current methods of
bioconfinement are imperfect and are unlikely to adequately restrict
gene flow (Refs. 25 and 53). The Agency asked the 2004 SAP whether the
condition that ``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)'' would be necessary
and/or sufficient to minimize the potential for a PVCP-PIP to harm the
environment through gene transfer from the crop plant containing the
PVCP-PIP to wild or weedy relatives. The Panel ``accepted that tactics
aiming at diminished gene exchange are highly desirable and even
necessary but are not sufficient'' (Ref. 25).
[[Page 19611]]
In spite of such concerns, EPA is still considering whether a
criterion involving biocontainment could be sufficient to enable the
Agency to determine with review that a product presents low risk with
respect to concerns associated with weediness. The 2005 SAP concluded
``that if highly effective biological containment and biological
mitigation methods could be deployed concurrently with the PVCP-PIP,
then it would be possible to exempt crops with sexually compatible wild
relatives. This opinion is different from the opinion of the October
2004 FIFRA SAP. The [2005] Panel concluded that this difference is
probably due to advances in containment and mitigation strategies. For
this reason, exemptions might be granted to any crop that hybridizes
with a wild relative in the US, its possessions or territories, if the
F1 and BC (backcross) hybrids have very low fitness such
that it is effectively lethal. Additionally, an exemption might be
possible if specific genes for lowering fitness are in tandem
constructs with the PVCP-PIP gene in such a way that they cannot
readily segregate from each other. The Panel did not determine what
level of effectiveness would be required but, it was agreed that
stacked strategies would reduce the cumulative risk, and should be
strongly considered'' (Ref. 11).
Bioconfinement strategies are known to have a wide range of
efficacy, and no standard level of efficacy to ensure environmental
safety has been determined (Ref. 53). Additionally, some techniques may
introduce risk concerns that must be evaluated, e.g., unintended
impacts on wildlife that eat seeds or pollen (Ref. 25). However,
scientific advancements may make bioconfinement techniques sufficiently
reliable and safe in the future such that deployment with a PVCP-PIP
would be sufficient to reach a low risk finding with respect to
concerns associated with weediness (Refs. 54 and 55). Therefore, EPA is
still considering a condition such as characteristic (2) proposed in
1994 that would constitute an alternative way to meet Sec.
174.27(a)(2) under any of the options discussed in this Preamble. For
example, Sec. 174.27(a)(2) might read:
The Agency determines after review that the plant containing the
PIP:
(i) Has no wild or weedy relatives in the United States with
which it can form viable hybrids in nature or employs a highly
effective biological containment technique.
(ii) Is not a weedy or invasive species outside of agricultural
fields in the United States or employs a highly effect biomitigation
construct that ensures escapes from cultivation are too unfit to
compete with wild-types.
EPA believes that characteristic (3) of the option proposed in 1994
is sound conceptually. However, the Agency's intent in developing this
exemption has historically been to have criteria that identify low risk
PVCP-PIPs such that the criteria could be evaluated with information
that a developer is likely to have acquired in the course of developing
the product and not require significant data generation. The Agency
presented a similar criterion to the 2004 SAP for their consideration:
``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.'' The Panel members
suggested that such a criterion would be difficult to implement in a
clear and transparent exemption review process given that ``[t]he Panel
had particular difficulty when attempting to add precision to
approaches that should be followed when sampling wild and weedy
relatives for the occurrence of specific virus tolerance or resistance
as specified by the Agency.''
As an alternative to a criterion like that described by
characteristic (3) in the 1994 proposal whose evaluation would
necessitate collection of potentially significant amounts of data, EPA
presented another option to the 2005 SAP: ``(i) the plant containing
the PVCP-PIP is itself not a weedy or invasive species outside of
agricultural fields in the United States, its possessions, or
territories, and (ii) the plant containing the PVCP-PIP does not have
relatives outside of agricultural fields in the United States, its
possessions, or territories that are weedy or invasive species or
endangered/threatened species with which it can produce viable hybrids
in nature'' (Ref. 11). However, the Panel concluded that ``the
probability that a particular transgene alters the dynamics of a wild
relative cannot be predicted by the current status of the wild species
as weedy, invasive, or threatened/endangered. The Panel agreed that the
criteria proposed by the Agency would not correctly identify PVCP-PIPs
which pose unacceptable environmental risks'' (Ref. 11). EPA has
therefore concluded that the Agency is unable at this time to
articulate a clear criterion for exemption that would expand the
eligible plants beyond those roughly described by the ideas in the 1994
characteristic (1) unless the Agency were to adopt a criterion whose
evaluation involved conducting a risk assessment of the PVCP-PIP/plant
combination such as it put forth in this preamble as the fourth option
for proposed Sec. 174.27(a)(2), i.e., that the PVCP-PIP is unlikely to
significantly change the population size or distribution of the species
containing the PVCP-PIP outside of agricultural fields or the
population size or distribution of any wild or weedy species in the
United States that could acquire the PVCP-PIP through gene transfer
(discussed in Unit III.C.2.iii.d.).
The other alternative proposed in 1994 did not contain a criterion
addressing concerns associated with gene flow. This option proposed a
full categorical exemption for all PVCP-PIPs (59 FR 60503). This option
is no longer the Agency's preferred approach for a number of reasons.
Specifically, EPA has received scientific advice since issuance of the
1994 proposal calling into question the Agency's 1994 rationale that
all PVCP-PIPs meet the FIFRA 25(b)(2) exemption standard, including
gene flow considerations. Although EPA believes that many PVCP-PIPs
present low risk and thus meet the FIFRA 25(b)(2) exemption standard,
in order to categorically exempt all PVCP-PIPs, the Agency must be able
to draw this conclusion for all PVCP-PIPs. Advances in scientific
understanding since 1994 suggest it may not be possible to support this
rationale for all PVCP-PIPs and that certain PVCP-PIPs may pose a
greater level of risk than is characteristic of the group as a whole.
For example, virus resistance is common in natural plant populations as
evidenced by conventionally bred virus resistant plants that are only
possible due to naturally existing resistance in crop and wild relative
populations (Ref. 20). This fact suggests that acquisition of virus
resistance is often unlikely to introduce a novel trait into many plant
populations. However, some notable exceptions to the ubiquity of virus
resistance in natural plant populations exist including the lack of
successful conventionally bred resistance to barley yellow dwarf virus
in major crops and the lack of natural resistance in some wild
relatives of these crops (Ref. 36). Such information suggests that
acquisition of a PVCP-PIP by such wild relatives of these plants has
the potential to free these wild relatives from what may be an
important ecological constraint. The conclusions of the 2004 FIFRA SAP
are consistent with the idea that it may not be possible to apply a
general exemption rationale to all PVCP-PIPs. The report concluded that
``...PVCP-PIPs [have] no inherent capacity to harm the environment.''
However, ``[i]t was recognized that knowledge of hybridization
potential was sparse and of very unequal quality but the likelihood of
serious economic
[[Page 19612]]
harm was such that some plants engineered to contain stress tolerant
traits should not be released'' (Ref. 25). The 2005 SAP's conclusions
discussed above also clearly suggest that crops containing a PVCP-PIP
that have wild relatives must be carefully considered on a case-by-case
basis (Ref. 11). Similarly, the 2000 National Research Council (NRC)
report recommended that because of concerns associated with
hybridization with weedy relatives, ``EPA should not categorically
exempt viral coat proteins from regulation under FIFRA. Rather, EPA
should adopt an approach, such as the agency's alternative proposal...,
that allows the agency to consider the gene transfer risks associated
with the introduction of viral coat proteins to plants'' (Ref. 10).
D. Viral Interactions
1. Scientific issues. In addition to weediness, a key issue
associated with PVCP-PIPs is the question of whether they could affect
the epidemiology and pathogenicity of plant viruses. Given the
potential impact of virus infection, such changes might affect
competitiveness of plant populations thereby altering ecosystem
dynamics, e.g., through significant changes in species composition of
populations, resource utilization, or herbivory.
The genetic material of plant viruses may be composed of either RNA
or DNA, although most have RNA genomes (Ref. 56). Although there are
significant differences between RNA and DNA viruses, both are obligate
parasites that usually move from plant to plant via vector-mediated
transmission. Such transmission, in connection with other types of
virus transmission, commonly leads to mixed viral infections in crops
and other plants (Ref. 57). In natural, mixed infections, viral genomes
from different strains and/or different species simultaneously infect
the same plant and thus have opportunities to interact (e.g., through
recombination, heterologous encapsidation, or synergy). In spite of
many opportunities for interaction in nature, such events rarely lead
to any detectable adverse outcome (Ref. 58). However, such in planta
interactions have the potential to result in a virus that causes
increased agricultural or other environmental damage.
In transgenic plants containing PVCP-PIPs, every virus infection
can be considered in one sense to be a mixed infection with respect to
the coat protein gene (Ref. 59). The key questions facing EPA are
whether interactions between such introduced plant virus sequences and
infecting viruses in transgenic plants may increase in frequency or be
unlike those expected to occur in nature (Ref. 60). The Agency has
written a literature review addressing these questions (Ref. 60) and
will briefly describe the issues associated with recombination,
heterologous encapsidation, and synergy below. EPA provides a general
overview of each of the processes separately, followed by a brief
review of relevant field studies that investigated these processes.
i. Recombination. Recombination is a natural process that can occur
during replication of DNA or RNA whereby new combinations of genes are
produced. Plant virus recombination can occur between members of the
same virus pathotype in natural infections, contributing to the number
of variants that exist within that pathotype. Recombination can also
occur when different viruses coinfect the same plant and interact
during replication to generate virus progeny that have genetic material
from each of the different parental genomes. Although recombination
likely occurs regularly in mixed viral infections, recombination only
rarely leads to viable viruses and even more rarely to viruses with
truly novel behavior and/or characteristics or any detectable adverse
outcome. In order to persist in nature, a recombinant virus must be
competitive with variants of the parental viruses that have already
demonstrated success in all stages of the infective cycle, e.g.,
transmission, gene expression, replication, and assembly of new virions
(Ref. 58). An analysis of cucumber mosaic virus (CMV) isolates in
natural populations showed that viable recombinants were very rarely
recovered in mixed infections (Ref. 61).
Although selection in the field appears to act against persistence
of new, recombinant viruses, recombination is thought to play a
significant role in virus evolution, presumably because recombinant
viruses are on very rare occasions able to outcompete existing viruses.
How a virus with increased pathogenicity or altered epidemiology might
conceivably be created through recombination was suggested by a
laboratory experiment in which a pseudorecombinant strain was created
by experimentally combining regions of the CMV and tomato aspermy virus
(TAV) genomes. This artificially manipulated virus was found to cause
more severe symptoms than either of the parental genomes, although the
recombinant was not a fully-functional virus as it was not able to move
beyond the initially infected cells (Ref. 62) and would therefore not
be expected to persist in nature. Another laboratory experiment has
shown interspecific recombination between CMV and TAV under conditions
in which recombinants would not be expected to have any particular
fitness advantage (Ref. 63). In another example, alteration of the host
range of tobacco mosaic virus (TMV) occurred when a chimeric virus
expressed the coat protein from alfalfa mosaic virus (AMV) instead of
its own (Ref. 64).
Evidence of past recombination having led to the creation of new
RNA viruses has been documented in a number of different groups
including bromoviruses (Ref. 65), luteoviruses (Ref. 66), nepoviruses
(Ref. 67), and cucumoviruses (Ref. 68). Sequence analysis of viruses
from the family Luteoviridae indicated that this family has evolved via
both intra- and interfamilial recombination (Ref. 69). Interspecific
recombination between two related potyviruses, soybean mosaic virus
(SMV) and bean common mosaic virus (BCMV) apparently led to the
creation of watermelon mosaic virus (WMV) with a broader host range
than either SMV or BCMV (Ref. 70). Whereas these latter two viruses are
generally restricted to Leguminosae, WMV has one of the broadest host
ranges among the potyviruses being able to infect both monocots and
dicots. For RNA viruses, evidence of recombinant viruses arising in
recent history has not been reported, suggesting that recombination as
a factor in RNA virus evolution may generally only be significant over
a longer timescale.
Recombination has also played a role in the evolution of new DNA
viruses including caulimoviruses (Ref. 71) and geminiviruses (Refs. 72
and 73). For DNA viruses, geminiviruses in particular, several
instances can also be cited in which relatively recent recombination
events appear to have resulted in the creation of new viruses. For
example, a recent epidemic of severe cassava mosaic disease in Uganda
is thought to be due to the combination and/or sequential occurrence of
several phenomena including recombination, pseudorecombination, and/or
synergy among cassava geminiviruses (Ref. 72). It also appears that
tomato-infecting begomoviruses that have emerged in the last 20 years
around the Nile and Mediterranean Basins probably resulted from
numerous recombination events (Ref. 74). In addition, a natural
recombinant between tomato yellow leaf curl Sardinia virus and tomato
yellow leaf curl virus was detected in southern Spain with a novel
pathogenic phenotype that might provide it with selective advantage
over the parental genotypes (Ref. 75). Finally, analysis of
[[Page 19613]]
a newly described Curtovirus species associated with disease of spinach
in southwest Texas suggests that it may be the result of recombination
among previously described Curtovirus species (Ref. 76).
In addition to virus-virus recombination, recombination has also
been found to occur between virus and plant host RNA. Sequence analysis
of the 5' terminal sequence of potato leafroll virus (PLRV) suggests
that it arose via recombination with host mRNA (Ref. 77). Evidence
suggests that such recombination events can affect virus virulence (for
review see Ref. 78). Like a plant host genome, transcripts of viral
transgenes would be available for recombination with infecting viruses,
and portions of the transgene could thus be incorporated into the
replicating virus. Several laboratory experiments have investigated the
potential for recombination between viral transgenes and infecting
viruses of the same species. These experiments show that recombination
can occur between viral transgenes and both RNA viruses (Refs. 79, 80,
81, 82, and 83) and DNA viruses (Refs. 84, 85, 86, and 87). However,
the relevance to PVCP-PIPs of the latter experiments with DNA viruses
is unclear because the transgenic plants used in the experiments
actually show no viral resistance; attempts to develop transgenic DNA
virus-resistant plants in general have had little success (Ref. 57). In
addition, to facilitate the detection of recombinants, most of these
experiments were conducted under conditions of high selective pressure
favoring the recombinant, i.e., only recombinant viruses were viable.
The selective pressure under normal field conditions would likely favor
the parental viruses rather than a recombinant as parental viruses will
be competent in all of the functions needed for propagation and will
outnumber the new recombinant.
ii. Heterologous encapsidation. Heterologous encapsidation occurs
when the coat protein subunits of one virus surround and encapsidate
the viral genome of a different virus. The coat protein, possibly in
conjunction with other viral factors, is often essential for
transmission and responsible for conferring the high degree of vector
specificity. Therefore, a heterologously encapsidated viral genome may
be transmitted by the vectors of the virus contributing the coat
protein rather than the vectors of the virus contributing the viral
genome. For many viruses, transmission from plant to plant occurs by
insect vectors, and each virus tends to be transmitted by only one type
of insect (Ref. 1). To the extent that vectors visit different groups
of plants, vectors carrying a heterologously encapsidated viral genome
may carry it to a plant the virus does not normally encounter (Ref.
59).
Most evidence of heterologous encapsidation is derived from
laboratory or greenhouse studies. Even though there is a high frequency
of mixed infections in nature, most mixed infections do not lead to
heterologous encapsidation, and those virus interactions that do occur
tend to be very specific rather than random interactions between
unrelated viruses (Ref. 88). Only among some types of plant viruses is
heterologous encapsidation regularly observed. Its frequency depends on
the relationship between the viruses involved, being more likely to
occur among closely related viruses (Ref. 89). An expansion of aphid
vector specificity due to heterologous encapsidation was first observed
in plants infected with two different isolates of barley yellow dwarf
virus (BYDV; Ref. 90) and was later shown to be a general phenomenon
among these viruses in natural populations of several plant species
(Ref. 91). Heterologous encapsidation was also shown to occur in
potyviruses. An isolate of zucchini yellow mosaic virus (ZYMV) that is
normally non-aphid transmissible due to a transmission-deficient coat
protein was found to be transmitted by the aphid vector due to
heterologous encapsidation when in a mixed infection with another
potyvirus, papaya ringspot virus (Ref. 92). Heterologous encapsidation
is essential for movement of some viruses. For example, umbraviruses do
not encode a coat protein, and therefore transmission between plants
occurs through encapsidation by an aphid-transmissible luteovirus coat
protein (Ref. 93).
Heterologous encapsidation is considered a possible environmental
concern associated with PVCP-PIPs because of the potential that if a
virus is heterologously encapsidated by a PVC-protein, the viral genome
might be able to spread to plants the virus ordinarily had no means of
reaching and thus could not have infected. Experimental studies have
shown that some PVC-proteins in transgenic plants have the ability to
encapsidate even unrelated infecting viruses (Refs. 94, 95, 96, and
97). However, heterologous encapsidation involving a viral transgene
can only occur if an expressed coat protein possesses the appropriate
physical parameters to encapsidate the viral genome of infecting
viruses. When transgenic plants containing a PVCP-PIP display
resistance with very low or no levels of PVC-protein expression (e.g.,
due to PTGS), the probability of heterologous encapsidation would be
very small or non-existent. (For a more detailed discussion of PTGS and
suppression of gene silencing, see Unit II.E. above and Unit IV.F. of
the companion document also appearing in today's Federal Register.)
Environmental concerns associated with heterologous encapsidation
when PVC-protein is expressed appear to be largely mitigated by several
factors. One, the heterologously encapsidated viral genome may not be
able to replicate in the new host plant and could therefore not
actually infect it. In addition, if replication is possible in the new
plant, the replicating viral genome encodes for and thus would produce
its own coat protein rather than that which heterologously encapsidated
it. This virus would not be transmitted by the new vector that brought
the heterologously encapsidated genome to the new host plant. The
epidemiological consequences of such heterologous encapsidation would
thus be limited. Another consideration for some viruses is that
effective vector transmission may depend on more than the coat protein
(Refs. 98 and 99), requiring regions of the viral genome not included
in PVCP-PIPs as defined for this proposal, e.g., coat protein read-
through domains or helper factors. Thus, in such cases, the coat
protein that could potentially heterologously encapsidate another viral
genome would not contain all the parts necessary to lead to a change in
vector specificity. In addition, in large monocultures of crop plants,
a vector is most likely to move from plant to plant within the field
and to transmit even a heterologously encapsidated viral genome to a
plant that the virus is already able to infect (Ref. 98). Finally, as
with recombination, as long as the PVC-protein expressed in the
transgenic plant is from a virus that normally infects the plant in the
area where it is planted, the outcome of any heterologous encapsidation
that may occur is expected to be the same in transgenic plants as in
natural, mixed infections.
In addition to these considerations, EPA evaluated whether a virus
that is heterologously encapsidated and carried to a new host plant
might be exposed to a vector that feeds on the new host plant and
perhaps other plants the virus ordinarily could not access. EPA
considered whether this new vector might in some cases be able to
transmit the virus even though the virus would now be encapsidated in
its own coat protein, thereby expanding the virus' vector range. A new
vector could
[[Page 19614]]
possibly transfer the virus to new host plants, thus expanding the
plant host range as well (Ref. 57). EPA considers expansion of host
range through heterologous encapsidation to be an extremely unlikely
outcome because such an outcome depends on each event in a series of
rare events occurring. Should the probability of occurrence of any one
event in this series be zero, the adverse event of an expanded host
range would not occur. In addition to the events enumerated above,
additional events must also occur. First, a virus must be
heterologously encapsidated, an event that is possible only for some
viral genome-coat protein combinations. Second, a new vector must
transmit the encapsidated viral genome. Third, the transmission must be
to a new host plant. Fourth, the heterologously encapsidated viral
genome must be able to replicate in the new host plant. Fifth, the
resulting virus, now encapsidated in its own coat protein, must be
exposed to a new vector the virus never encountered before that is
nevertheless able to transmit it. Finally, this vector must transmit
the virus to a new plant that the virus' prior vectors never visited.
For such a series of events to be novel, the viruses, vectors, and
plants involved must have had no previous opportunity to interact, and
it is rare for such a condition to be met. For example, it is known
that many viruses are transmitted by polyphagous insects, which would
have already allowed the viruses to be introduced to many potential
plant species even in the absence of heterologous encapsidation (Ref.
57). Moreover, viruses may be transmitted at low frequency by a range
of species other than their primary vector or mechanically, e.g.,
through the practices of modern agriculture (Ref. 98).
Another scenario EPA considered is one where a high enough
frequency of vector transmission to a new host plant due to
heterologous encapsidation might mean that secondary spread among new
plant hosts might not be required for the phenomenon to affect the
population, assuming that the virus is able to decrease the new host
plant's growth and/or reproduction. Although this scenario may be more
likely to occur than an expansion of host range given that fewer rare
events would have to occur, any impact on the affected plant population
would be highly localized being confined to plants in or near
transgenic crop fields. Such negative impacts are unlikely to be
sufficiently detrimental to require FIFRA regulation given their
localized nature and the probability that common agricultural practices
(e.g., vector control) could be used to manage the problem. Moreover,
although isolated instances of transmission may occur, a significant
proportion of a plant population is unlikely to be infected in such a
scenario. For example, a field experiment (discussed in Unit
III.D.1.iv.) showed that heterologous encapsidation led to infection of
only 2% of plants compared to 99% of plants infected under similar
conditions by a virus that is not heterologously encapsidated (Ref.
100). Most importantly, the heterologously encapsidated virus will
still have no way to spread among or beyond the plants of the affected
population. In the case where a plant population contains relatively
few individuals such that the impact of single plant infections would
be magnified, plant infections are even less likely to occur because in
addition to the inefficient nature of heterologous encapsidation, the
vector would be more likely to feed on the more abundant transgenic
crop plants. In some cases a vector may have a strong preference for a
specific plant over even closely related plants (Ref. 101).
Finally, EPA evaluated whether after expansion to a new host, rapid
selection of variants best adapted to the new environment might lead to
the evolution of a new virus (Ref. 57). However, in addition to
requiring several of the rare events discussed above to occur, this
phenomenon is unlikely to be entirely novel in any circumstance. All
viruses that are occasionally heterologously encapsidated and
transmitted to a new plant host have had the opportunity to adapt to
new plant environments. The opportunities for rapid viral evolution
presented by transgenic plants containing PVCP-PIPs would not be
fundamentally different from what occurs in nature under reasonably
likely circumstances. Rapid viral evolution after heterologous
encapsidation is not dependent on the unique combination of viruses
that interact but rather the introduction of a virus to a new plant
host, an event that likely occurs in nature at some frequency for most
viruses either through heterologous encapsidation or through occasional
transmission that occurs mechanically or from secondary vectors (Ref.
98).
iii. Synergy. In synergy, another type of viral interaction, the
disease severity of two viruses infecting together is greater than
expected based on the additive severity of each virus alone. For
example, when a plant containing potato virus X (PVX) is coinfected
with any of a number of potyviruses including tobacco vein mottling
virus, tobacco etch virus, and pepper mottle virus, the disease
symptoms are considerably worsened and PVX accumulates to a greater
concentration (Ref. 102). A listing of reported viral synergisms has
been compiled (Ref. 103).
In developing this proposal, EPA addressed whether synergy could
occur between an infecting virus and a PVCP-PIP, thereby increasing the
severity of the infecting virus and whether any consequences for the
environment could result from such an increase. For disease severity to
worsen, the PVC-protein must be at least one of the factors causing
synergy. However, the coat protein is considered much less likely to be
responsible for synergism than other parts of the virus (Refs. 104 and
105), and a PVCP-PIP producing other viral proteins would not qualify
for this proposed exemption. In addition, any negative effects are
expected to manifest primarily in the transgenic crop itself.
Furthermore, any negative effects are expected to be self-limiting
because any plants containing a PVCP-PIP that is prone to display
synergy with viruses common in the areas of planting would be quickly
abandoned once such effects were detected, perhaps as early as the
field-testing stage of product development. Synergistic interactions
can be evaluated in transgenic plants before deployment by experimental
inoculation with all of the viruses likely to be encountered in the
field (Ref. 98). Developers have a strong incentive to undertake such
efforts to ensure the efficacy of their product after deployment.
iv. Field experiments. The experiments referenced in Units
III.E.2.i. through iii. above investigated potential viral interactions
in transgenic plants containing a PVCP-PIP under laboratory conditions.
However, equally important is consideration of the likelihood and
potential impact of viral interactions under natural field conditions
(Ref. 106). Relatively few field studies have been conducted to address
the questions EPA is evaluating for this proposal, but the Agency has
carefully considered the available literature in developing this
proposed exemption.
A 6-year experiment searched for and failed to find evidence of
interactions involving viral transgenes in 25,000 transgenic potato
plants transformed with various PLRV coat protein constructs. Plants
were exposed to infection by PLRV by direct inoculation, plant-to-plant
spread, or natural exposure. In field experiments, plants were also
naturally exposed to the complex of viruses that occur in the region.
Both the greenhouse and field tests failed to show any change in the
[[Page 19615]]
type or severity of disease symptoms, and all viruses isolated were
previously known to infect the plants and had the expected transmission
characteristics (Ref. 107). These results suggest that viral
interactions leading to evolution of new viruses and/or more severe
viral disease are events too rare to be detected in a field trial of
this size and duration.
A 2-year experiment with transgenic melon and squash expressing
coat protein genes of an aphid-transmissible strain of CMV failed to
yield evidence that either recombination or heterologous encapsidation
enabled spread of an aphid non-transmissible strain of CMV in the field
(Ref. 108). A similar experiment used transgenic squash expressing coat
protein genes of an aphid-transmissible strain of watermelon mosaic
virus (WMV). Plants were mechanically inoculated with an aphid non-
transmissible strain of ZYMV, and subsequent transmissions of the virus
(assumed to be vectored by aphids) were assessed. Infections of ZYMV
were not detected in nontransgenic fields, but the virus infected up to
2% of plants in transgenic fields. Several lines of evidence suggested
ZYMV infection was mediated by the WMV PVC-protein heterologously
encapsidating the ZYMV viral genome. However, the virus spread over
short distances, and transmission at a low rate failed to lead to an
epidemic of ZYMV in fields of WMV-resistant transgenic squash despite
the presence of optimal conditions for transmission (Ref. 100). These
results support the contention that even if heterologous encapsidation
involving a PVC-protein were to occur, the impact is likely to be
negligible because each plant infection by a heterologously
encapsidated virus requires a series of rare events to occur. Viral
infection by normal routes of transmission can be at least an order of
magnitude more efficient and lead to relatively greater impacts (Ref.
100).
An experiment to assess the biological and genetic diversity of
California CMV isolates sampled before and after deployment of
transgenic melon containing the CMV coat protein gene documented only
one CMV isolate that had significant sequence changes. However, the
same change was seen with infection of non-transgenic plants,
suggesting that this isolate did not result from recombination between
the transgene and an infecting virus (Ref. 109). The only field
experiment to directly assess the effect of recombination in a
transgenic plant containing a PVCP-PIP found no detectable grapevine
fanleaf virus (GFLV) recombinants containing the inserted coat protein
sequence over the course of a 4-year study (Ref. 110). Test plants
consisted of nontransgenic scions grafted onto transgenic and
nontransgenic rootstocks that were exposed over 3 years to GFLV
infection at two locations. Analysis of challenging GFLV isolates
revealed no difference in the molecular variability among isolates from
190 transgenic and 157 nontransgenic plants, or from plants within (253
individuals) or outside (94 individuals) of the two test sites.
2. Proposed exemption criterion. The information in Units
III.E.2.ii. through iv. suggests that heterologous encapsidation very
rarely leads to changes in virus epidemiology that could have any
large-scale impact and that synergy in plants containing PVCP-PIPs is
also unlikely to cause any widespread environmental harm. Consistent
with these observations, the 2004 SAP noted that ``except perhaps for a
very few cases, neither heterologous encapsidation nor synergy should
be considered to be of serious concern'' (Ref. 60). However, the Agency
believes that in all cases, concerns associated with these types of
viral interactions are likely to be limited in scope (for reasons
discussed in Units III.E.2.ii. through iii.) such that the
determination can be made that they pose low risk to human health and
the environment. EPA therefore concludes that PVCP-PIPs present low
risk with respect to heterologous encapsidation and synergy and that
PVCP-PIPs could be exempted without further qualification or
requirements to address these endpoints.
However, EPA is not able to conclude at this time that all PVCP-
PIPs are low risk with respect to recombination (although see Unit VII
for a discussion of EPA's request for information that might allow the
Agency to reach such a conclusion). The Agency notes that the vast
majority of interactions between a viral transgene and an infecting
virus are expected to be no different from those that would occur in a
natural mixed infection of the respective viruses and would not cause
any adverse environmental effects beyond what could occur in the
absence of the PVCP-PIP. Nevertheless, the information discussed in
Unit III.D.1.i. suggests that recombination among viruses may lead to
rare instances of adverse changes in virus epidemiology and/or
pathogenicity, e.g., a host range expansion. Based on the available
information, EPA is not able to rule out that viable, recombinant
viruses containing a portion of a PVCP-PIP could arise in transgenic
plants and that in a small set of circumstances (discussed in Unit
III.D.2.i.) such recombinants could be unlike those that could arise
naturally. EPA agrees with the conclusions of the 2004 SAP that ``[i]n
contrast to heterologous encapsidation and synergy, at least in theory,
the impact of recombination could be much greater, since there is now
abundant bioinformatic evidence that recombination has indeed, as long
suspected, played a key role in the emergence of new viruses over
evolutionary time'' (Ref. 25). The 2005 SAP concurred with this
conclusion by noting that there ``are a few scenarios, however, in
which recombination may have an incrementally higher probability of
creating a virus with new properties. In conclusion, the Panel
recommended the need for the Agency to have criteria to assess the
level of risk'' (Ref. 11).
The Agency notes that the 2005 SAP concluded that ``the likelihood
for `novel' interactions is very low, and the environmental concerns
that might result from using PVCP-PIPs in the United States... is lower
than that which occurs naturally from mixed virus infections'' (Ref.
11). In addition, ``it was repeatedly stated that the consequences of
any recombination event are minimal. This conclusion was based on the
fact that nearly every plant on the planet is harboring multiple virus
infections with both closely related and taxonomically distinct
viruses, with essentially no new viruses emerging with substantially
different properties and causing wide pandemics or undesirable
environmental effects'' (Ref. 11). In spite of such comments, EPA's
proposal contains Sec. 174.27(b) because of the overall context of the
Panel's response which articulated several factors (discussed in Unit
III.D.2.) that should be considered when evaluating recombination. EPA
believes Sec. 174.27(b) is consistent with these comments of the 2005
SAP because the Agency believes these comments apply only when
considering the whole set of PVCP-PIPs that are likely to be developed.
For the PVCP-PIPs that would only qualify for an exemption without the
limitations provided by Sec. 174.27(b), EPA does not believe the
Agency can conclude low risk with respect to recombination because the
2004 and 2005 SAPs have identified specific instances where this
general conclusion may not hold.
The few field evaluations conducted (discussed in Unit III.D.1.iv.)
suggest that adverse environmental effects due to recombination in
transgenic plants containing PVCP-PIPs are unlikely to occur at least
on a small scale over a short time period. However, large acreages of
plants containing a PVCP-
[[Page 19616]]
PIP grown over many years may provide increased opportunity for rare
events to occur that are unlikely to be detected in experimental
studies (Ref. 104). In addition, none of the experimental systems
described above would be predicted to involve viruses that would
otherwise not be expected to interact in a mixed infection found in
nature. Given the limited amount of field data available, particularly
data relevant to the circumstances EPA has identified as being of
highest concern (i.e., those that could lead to novel interactions),
EPA is limiting the proposed exemption to those PVCP-PIPs for which
novel viral interactions are unlikely to occur. When EPA consulted the
2004 SAP about situations in which novel viral interactions might be a
concern, the Panel agreed ``that recombination is a concern when the
two contributing viruses have not previously had a chance to
recombine'' (Ref. 25).
In addition to considering the potential for novel viral
interactions to occur, EPA also considered whether transgenic plants
containing PVCP-PIPs might have a changed frequency of viral
interactions. The frequency could decrease because the cellular
concentration of viral RNA transcripts expressed from transgenes may be
orders of magnitude lower than the concentration of viral RNA commonly
found in natural, mixed infections (Ref. 111), reducing the opportunity
for recombination. The concentration of infecting viral RNA from the
target virus would also be reduced considerably if the PVCP-PIP is
efficacious, particularly when the mechanism of resistance relies on
PTGS to remove viral RNA transcripts with homology to the transgene
(Ref. 112), thereby also reducing the opportunity for recombination.
However, the frequency of interactions could also increase given that
transgene RNA expressed from a constitutive promoter could be available
for interactions with infecting viruses in all cells of the plant at
all times - unlike RNA from a virus in a natural infection. When a
virus invades a cell, it often replicates and then moves to other cells
within the plant. The RNA remaining in the initially infected cell
becomes encapsidated and may no longer be available for interactions
with another invading virus (Ref. 113). When EPA presented this issue
to the 2004 SAP, the panel responded that ``no increase in heterologous
encapsidation should be anticipated in PVCP-PIP plants'' and ``the
Panel believed that in general recombination was more likely to occur
in transgenic plants than in non-bioengineered plants.'' Nevertheless,
the Panel agreed ``that the important questions are not the relative
likelihood for recombination to occur, but rather whether recombinants
in transgenic plants are different from those in non-transgenic plants
and whether they are viable'' (Ref. 25). Thus, EPA's proposal focuses
on situations in which novel recombination events could occur due to
the presence of a PVCP-PIP.
i. Proposed categorical exemption criterion in Sec. 174.27(b)(1).
In developing the proposed categorical exemption for a subset of PVCP-
PIPs in which a developer could self-determine whether the criteria
were met, EPA sought to clearly identify those situations that pose low
risk with respect to viral interactions.
A PVCP-PIP would meet the viral interactions criterion under Sec.
174.27(b)(1) if:
(i) The viral pathotype used to create the PVCP-PIP has
naturally infected plants in the United States and naturally infects
plants of the same species as those containing the PVCP-PIP, or
(ii) The genetic material that encodes the pesticidal substance
or leads to the production of the pesticidal substance is inserted
only in an inverted repeat orientation or lacking an initiation
codon for protein synthesis such that no PVC-protein is produced in
the plant.
Recombination between the coat protein gene of the PVCP-PIP and
infecting viruses would be expected to be of little concern in certain
instances: when such recombination would involve segments of viruses
that are judged likely to have had the opportunity to recombine in a
natural, mixed infection (and therefore any recombinants produced are
unlikely to be novel), and when PTGS results in only small, cleaved
pieces of RNA being available for recombination. The former situation
would be met if the conditions of the criterion in proposed Sec.
174.27(b)(1)(i) are met. The latter situation would be met if the
conditions of the criterion in proposed Sec. 174.27(b)(1)(ii) are met.
EPA is proposing that no further data or information would be needed to
evaluate risks associated with recombination when Sec. 174.27(b)(1) is
satisfied under either Sec. 174.27(b)(1)(i) or Sec. 174.27(b)(1)(ii),
and therefore no Agency review would be necessary. The developer may
make this determination.
If the viral pathotype used to construct the PVCP-PIP was isolated
in the United States from the same plant species as was engineered to
contain the PVCP-PIP, the PVCP-PIP would meet the proposed criterion in
Sec. 174.27(b)(1)(i). It should be noted that this proposed criterion
would be used in concert with the proposed protein production criterion
in Sec. 174.27(c) discussed below in Unit III.E.2., which ensures that
any modifications from the natural isolate encode a protein that is no
more than minimally modified from a natural virus coat protein. Thus,
any coat protein that satisfies Sec. 174.27(c) would be extremely
unlikely to confer significantly different properties on any virus that
could potentially acquire the coat protein through recombination with
the genetic material of the PVCP-PIP.
The Agency asked the FIFRA SAP during the October 2004 meeting to
what extent PVCP-PIPs in plants might present a potential concern
should interactions with infecting viruses occur. The Panel expressed
concern only ``about certain limited situations'' and clarified that
``in most cases there is little a priori reason to believe that
recombinants between viruses and transgenes will be more of a problem
than recombinants between two viruses infecting the same plant, unless
transgenes are derived from severe or exotic isolates. The general
recommendation to use mild, endemic isolates as the source of the
transgene (e.g. Hammond et al. 1999) should minimize any potential for
creation of novel isolates that would not equally easily arise in
natural mixed infections'' (Refs. 25 and 57). The Agency's proposed
Sec. 174.27(b)(1)(i) is consistent with this 2004 SAP recommendation
because it excludes exotic virus isolates as the source of the PVCP-PIP
transgene. Although proposed Sec. 174.27(b)(1)(i) does not require
that the virus isolate be a ``mild'' form of the virus, it does ensure
that when virus isolates capable of causing severe cases of viral
disease are used, the PVCP-PIP may only meet Sec. 174.27(b)(1)(i) if
the viral pathotype was present in the natural system and therefore
should pose no risk of novel interactions.
The 2005 SAP offered a decision flowchart indicating a point at
which the Agency should identify the few scenarios where recombination
may be of concern: ``the question arises as to whether recombination of
the sequence could lead to a significant change in the properties of
the recombinant over the original properties of the superinfecting
virus. Significant changes include increase in pathogenicity, increase
of host range or change of vector'' (Ref. 11). EPA believes that
consideration of whether the conditions of proposed Sec.
174.27(b)(1)(i) are met addresses whether the potential exists for
significant changes in the properties of a recombinant virus compared
to what
[[Page 19617]]
might occur in a natural, mixed infection.
In addition to excluding exotic virus isolates, proposed Sec.
174.27(b)(1)(i) also excludes PVCP-PIPs that are inserted into a plant
species that is not naturally infected by the virus used to create the
PVCP-PIP. Most PVCP-PIPs are created from viruses that do naturally
infect the plant species into which they are inserted because greater
efficacy is achieved when a virus most similar to the target virus is
used as the source of the sequence used in the PVCP-PIP. However,
virus-resistant transgenic plants have been created where this is not
the case (Ref. 114). In these situations, a virus is introduced into a
system where it does not naturally occur, and viruses with which it
does not otherwise interact may be present in that system. The Agency
cannot a priori determine that such interactions are safe because there
is no experience upon which to base such a finding.
Proposed Sec. 174.27(b)(1)(i) is also consistent with the 2005
SAP's recommendation to consider ``whether recombination of the
sequence could lead to a significant change in the properties of the
recombinant over the original properties of the superinfecting virus''
(Ref. 11). When the viral pathotype used to create the PVCP-PIP has
naturally infected plants in the United States and naturally infects
plants of the same species as those containing the PVCP-PIP, the
sequences that could interact would be expected to already have
opportunities to interact in nature and thus no novel recombinants
should be produced.
The Agency's proposed Sec. 174.27(b)(1)(ii) is consistent with the
2005 SAP's recommendation to consider whether the PVCP-PIP expresses
PVC-protein when evaluating the potential consequences of recombination
(Ref. 11). When a PVCP-PIP expresses no PVC-protein because it is
designed to mediate resistance through PTGS, recombination would be of
little concern because ``recombination between a full-length viral RNA
and a cleaved small RNA resulting from PTGS would yield a truncated
non-functional RNA. Therefore, a PTGS transgene poses negligible
potential to yield novel recombinant viruses'' (Ref. 11). EPA therefore
makes part of its proposal two circumstances when, according to the
2005 SAP, the PVCP-PIP can only mediate resistance through PTGS because
it would produce no PVC-protein: when the genetic material that encodes
the pesticidal substance or leads to the production of the pesticidal
substance is inserted only in an inverted repeat orientation or lacking
an initiation codon for protein synthesis such that no PVC-protein is
produced in the plant (Ref. 11). See Unit III.D.2.ii. below for a
discussion of how other constructs mediating resistance through PTGS
could meet Sec. 174.27(b).
One Panel member noted, ``PTGS results in small RNA from the PIP
and the infecting virus that could, in certain circumstances, be
recombinatorial.'' However, the Panel concluded ``this minimal RNA
would not confer a phenotype to the recombinant, would result in just a
few nucleotide changes in a potential recombinant, and thus would be
irrelevant'' (Ref. 11).
EPA proposes to define the term ``naturally infect'' to mean ``to
infect by transmission to a plant through direct plant-to-plant contact
(e.g., pollen or seed), an inanimate object (e.g., farm machinery), or
vector (e.g., arthropod, nematode, or fungus). It does not include
infection by transmission that occurs only through intentional human
intervention, e.g., manual infection in a laboratory or greenhouse
setting.'' The Agency is proposing this definition specifically to
exclude transmission that occurs only through intentional human
intervention because such transmission would have little relevance to
normal virus infection. EPA recognizes that humans may play an
inadvertent role in infection (e.g., by transmitting the virus on farm
machinery). Such unintentional (and often unavoidable) transmission can
be an important means of virus transmission, leading to the natural
presence of viruses in plants. EPA therefore proposes to include this
mode of incidental transmission in the definition of naturally infect.
EPA uses the term ``viral pathotype'' rather than the more generic
term ``virus'' in response to the October 2004 FIFRA SAP comment that
``[n]ot all isolates of a virus infect and cause disease in all plant
genotypes and, as a consequence, the unqualified use of the term
`virus' when setting a condition for applicants to the Agency [is] not
adequate in this context. It is therefore appropriate in the context of
biosafety as well as virus epidemiology to recognize the value of
defining specific viral pathotypes or host range variants.'' The 2005
SAP was asked to comment on the use of this term and responded, ``there
was not much discussion of this term. The Panel suggested that logic
says that local or indigenous virus isolates, or those with significant
sequence similarity, will be used to generate PVCP-PIPs. From what we
know now, only those viruses with high sequence identity will be useful
as sources of the PVCP-PIP transgene.'' EPA agrees that generally viral
pathotypes that meet Sec. 174.27(b)(1) will be those most effective
for creating PVCP-PIPs and will therefore be the most commonly used.
However, EPA considers the limitations imposed by this term to be
necessary because the Agency cannot conclude that viruses not meeting
this criterion would be low risk with respect to recombination.
In this proposed criterion and in Sec. 174.27(c) discussed below,
EPA uses the phrase ``genetic material that encodes the pesticidal
substance or leads to the production of the pesticidal substance,''
rather than the phrase ``genetic material necessary for the
production,'' to indicate that regulatory regions, such as promoters,
enhancers, or terminators, need not be considered in evaluating whether
a PVCP-PIP satisfies these criteria. EPA is not proposing to amend the
definitions for ``genetic material necessary for the production'' or
``regulatory region,'' both found at 40 CFR 174.3, and is not seeking
any comment on these definitions.
ii. Proposed exemption criterion conditional on Agency
determination in Sec. 174.27(b)(2). The Agency recognizes that many
PVCP-PIPs may pose low risk with respect to recombination even though
they fail to satisfy Sec. 174.27(b)(1). Therefore, EPA is proposing an
approach under which PVCP-PIPs that fail to meet Sec. 174.27(b)(1)
could still meet Sec. 174.27(b), subject to an Agency review to
determine whether they meet a different set of conditions related to
this issue. Under this proposed approach, a PVCP-PIP would meet Sec.
174.27(b) under Sec. 174.27(b)(2) if the Agency determines that
viruses that naturally infect the plant containing the PVCP-PIP are
unlikely to acquire the coat protein sequence through recombination and
produce a viable virus with significantly different properties than
either parent virus.
The conditions in proposed Sec. 174.27(b)(1) address the potential
for recombinants to arise unlike those expected in natural mixed
infections primarily by ensuring that no novel viral interactions
occur. Under proposed Sec. 174.27(b)(2), a PVCP-PIP could qualify for
exemption even when novel viral interactions could occur providing
steps were taken to ensure that an infecting virus would not acquire a
portion of the PVCP-PIP coat protein sequence through recombination and
produce a viable virus with significantly different properties than
either parent virus.
Experimental evidence has suggested a number of ways coat protein
genes of certain viruses may be modified in constructing a PVCP-PIP to
reduce the possibility they would participate in a
[[Page 19618]]
recombination event with an infecting virus. For example, removing the
3' untranslated region (UTR) in the coat protein mRNA transcript may be
effective at reducing recombination for viruses that carry the
initiation promoters of RNA replication in this region (Ref. 115).
Evidence suggests that recombination among RNA viruses occurs via
template switching by the viral replicase during replication such that
a hybrid molecule is formed (Ref. 116). Inclusion of the 3' UTR may
enable replication to begin on the mRNA transcript and then switch to
the RNA of the invading virus. Removal of this region would necessitate
two separate template-switching events to form a successful recombinant
and thus reduce its likelihood of occurrence (Ref. 80). Experiments
with CCMV demonstrated that deletions in the 3' UTR did indeed reduce
the recovery of recombinant viruses (Ref. 117). Since functional
resistance is still conferred by constructs containing a CP lacking the
3' UTR, this region may not be necessary. Other techniques that have
been suggested include:
Reducing the extent of shared sequence similarity between
the infecting virus and the transgene to reduce the opportunities for
homologous recombination (Ref. 118).
Excluding any sequences containing replicase recognition
sites that are potential sites of recombination and any sequences known
or thought to be recombination hotspots, e.g., promoters for genomic
and subgenomic RNA synthesis (Ref. 119).
Avoiding potential hairpin structures in the transgene
that might function as acceptor structures for the replicase complex
(Ref. 120).
It is important to note that any PVC-protein produced must be
evaluated under Sec. 174.27(c) in order for the PVCP-PIP to qualify
for exemption. Some techniques that may enable a PVCP-PIP to meet Sec.
174.27(b)(2) would preclude the PVCP-PIP from meeting Sec.
174.27(c)(1) and necessitate a review under Sec. 174.27(c)(2). For
example, a construct could meet proposed Sec. 174.27(b)(2) if it
contained portions of several different coat protein genes in tandem,
linked together in such a way that if the sequence were translated it
would yield a non-functional coat protein of no use to a virus. A virus
that acquired this entire sequence through recombination in exchange
for portions of its own genome would likely be nonviable. As another
example, a construct might meet proposed Sec. 174.27(b)(2) if it
contained a very small portion of a coat protein gene. In such cases, a
virus would be unlikely to acquire this sequence through recombination
without picking up additional pieces of genetic material from the
construct or the plant genome that would likely render the virus
nonviable. Or, if a virus did acquire a piece of just the small part of
the coat protein sequence contained in the transgenic plant, it would
likely not be large enough to significantly change the properties of
the parent virus. Any PVC-protein produced from either such construct
would fail to meet Sec. 174.27(c)(1) but could be evaluated under and
may nevertheless meet Sec. 174.27(c)(2) (see Unit III.E.2. below).
EPA recognizes the comments of the 2004 SAP that ``methods for
minimizing recombination are only partially effective. For this reason,
the question remains whether novel recombinants would be created in
transgenic plants, and simply reducing the frequency of these events is
not an answer to the question'' (Ref. 60). However, EPA believes that a
combination of two or more methods, or even perhaps a single method in
some cases, could be employed to reduce the expected frequency of
recombination such that the Agency would be able to make a
determination that a PVCP-PIP would pose low risk with respect to viral
interactions. EPA asked the 2004 SAP ``which methods are sufficiently
effective such that requiring measurement of recombination rates would
be unnecessary. The Panel doubted if the... methods [discussed] are
sufficiently effective to warrant the reduction of recombination rates
below the level that the actual measurement will be unnecessary'' (Ref.
25). However, the Agency would have the opportunity during the case-by-
case Agency review under Sec. 174.27(b)(2) to consider the particular
viral system and whether literature supports the contention that the
recombination reduction techniques are likely to be sufficiently
effective in the system in which they are employed. EPA anticipates
that the Agency could base this determination on the expected reduction
in frequency of recombination as determined from the literature and
that actual measurement of recombination rates may be unnecessary.
Given that there is no universally applicable method for reducing
recombination frequency and this type of case-by-case consideration of
the particular virus system in question must be conducted, EPA believes
an Agency review is needed to make this determination. With an Agency
determination under Sec. 174.27(b)(2), EPA would create a criterion
that would encompass a larger set of those PVCP-PIPs that pose low risk
with respect to viral interactions than are covered under Sec.
174.27(b)(1).
Section 174.27(b)(2) is consistent with the advice of the 2005 SAP
in that it incorporates the portions of the proposed decision tree that
allow consideration of whether there are ``features controlling
recombination,'' whether ``the protein [is] complete,'' and whether the
plant host contains ``genes that reduce recombination'' (Ref. 11).
Likewise, the review procedures for determining whether a PVCP-PIP met
the conditions of Sec. 174.27(b)(2) would also be able to consider
``the type of RNA-dependent RNA polymerase (RdRps) encoded by the
superinfecting virus and the compartmentalization of its site of
replication'' as suggested by the 2005 SAP (Ref. 11). Although EPA
notes that there was some disagreement among the Panel members about
the appropriateness of including such information as part of the flow
chart, the Agency believes that this information could be reasonably
considered when available and when sufficient knowledge about the
plant/virus system exists such that it would offer useful information
for evaluating this criterion. Overall, Sec. 174.27(b) thus enables
the Agency to consider either under Sec. 174.27(b)(1) or Sec.
174.27(b)(2) all of the factors mentioned in the flowchart by the 2005
SAP.
3. Historical approaches still under consideration. EPA's proposed
exemption in 1994 did not contain any criteria related to viral
interactions. However, since that time, many additional scientific
papers and reviews have been published on this topic. Most affirm the
general safety of PVCP-PIPs with respect to viral interactions, but
some call into question assumptions of how generically this conclusion
holds across all PVCP-PIPs. For example, although the 2000 NRC report
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 NRC's
report also suggested that their conclusions were based on the
assumption that certain risk management strategies should or would be
implemented, e.g., elimination of specific sequences to limit the
potential for recombination (Ref. 10). EPA believes the Agency's 1994
conclusion of low probability of risk still holds for most PVCP-PIPs.
However, in order to grant an exemption under FIFRA, EPA must be able
to make such a finding for all PVCP-PIPs covered by the exemption and
must make its safety determination
[[Page 19619]]
in the absence of any regulatory oversight under FIFRA that could
ensure mitigation measures, such as those discussed in the NRC report,
were employed. Therefore, it appears prudent at this time to limit this
proposed exemption with a criterion that restricts the potential for
novel recombination events, as these have been identified as the rare
situation in which viral interactions in plants containing a PVCP-PIP
may lead to adverse environmental effects.
EPA presented a set of conditions to the 2004 SAP and asked whether
they would significantly reduce either the novelty or frequency of
viral interactions in plants containing PVCP-PIPs such that the Agency
would not need to regulate the PVCP-PIP (Ref. 25). The first proposed
condition was that ``the genetic material of the PVCP-PIP is translated
and/or transcribed in the same cells, tissues, and developmental stages
naturally infected by every virus from which any segment of a coat
protein gene used in the PVCP-PIP was derived.'' EPA considered such a
condition because with a PVCP-PIP, plants may express viral genes in
cells and/or tissues that the virus does not normally infect. Genetic
promoters currently used in most transgenic plants cause constitutive
expression of transgenes at developmental stages that might otherwise
be unaffected by viral infection and often in tissues that the virus
does not normally infect (Ref. 113). For example, luteoviruses are
normally expressed only in phloem tissue, but the cauliflower mosaic
virus (CaMV) promoter, commonly found in existing PIP constructs, would
drive expression of luteoviral coat protein in all plant cells. Some
evidence suggests that in natural infections different viruses have
different temporal or spatial expression patterns that would limit
their interactions (Refs. 63, 121, and 122). However, the 2004 SAP
concluded that such a condition would be of limited utility because
``[m]ost plant viruses are present in a wide range of cell and tissue
types'' (Ref. 25).
The second condition proposed to the 2004 SAP was that ``the
genetic material of the PVCP-PIP contains coat protein genes or
segments of coat protein genes from viruses established throughout the
regions where the crop is planted in the United States and that
naturally infect the crop into which the genes have been inserted.''
EPA considered the first part of this criterion because plants may be
engineered with coat protein genes from an exotic strain of a virus
that may be more virulent or have other properties different from
endemic isolates. Interactions between a PVCP-PIP based on such virus
sequences and infecting viruses could potentially change the
epidemiology or pathogenicity of the infecting viruses. The 2004 SAP
concurred that ``using such an exotic coat protein gene would open
possibilities for novel interactions.'' EPA's current proposed Sec.
174.27(b) thus excludes from exemption PVCP-PIPs based on coat protein
genes from exotic viruses unless steps have been taken to reduce the
frequency of recombination.
EPA considered the second part of this 2004 criterion (i.e., the
genetic material of the PVCP-PIP contains coat protein genes or
segments of coat protein genes from viruses... that naturally infect
the crop into which the genes have been inserted) because in
heterologous resistance a plant may be resistant to infection by a
particular virus in spite of having the coat protein gene of another
virus incorporated into its genome. For example, coat protein genes
from LMV were used to provide resistance to PVY in tobacco which is not
infected by LMV (Ref. 114). In such plants, LMV sequences might have a
new opportunity to interact with viruses that infect tobacco. The 2004
Panel concluded that ``[w]hat is described here is most often
implemented: in designing a PVCP transgene, better efficacy is often
observed if it is as similar as possible to the target virus.''
Nevertheless, EPA believes that EPA's current proposed criterion (b) is
appropriate given that PVCP-PIPs may be developed using heterologous
resistance. This criterion excludes from exemption PVCP-PIPs used in
plants that the virus used to create the PVCP-PIP does not naturally
infect unless steps have been taken to reduce the frequency of
recombination.
The third condition proposed to the 2004 SAP was that ``the PVCP-
PIP has been modified by a method scientifically documented to minimize
recombination (e.g., deletion of the 3' untranslated region of the coat
protein gene). As discussed above, the 2004 SAP expressed reservation
about such a criterion, and EPA recognizes that any single method for
minimizing recombination may be only partially effective (Ref. 60).
However, EPA believes that a combination of two or more methods, or
even perhaps a single method in some cases, could be employed such that
the expected frequency of recombination would be reduced to a level
that would support determination that a PVCP-PIP would pose low risk
with respect to viral interactions, but that such a determination could
only be made on a case-by-case basis. EPA thus intends that the
proposed criterion in Sec. 174.27(b)(2)(ii) would allow the Agency to
make this determination after review.
The fourth condition proposed to the 2004 SAP was that ``the PVCP-
PIP has been modified by a method scientifically documented to minimize
heterologous encapsidation or vector transmission, or there is minimal
potential for heterologous encapsidation because no protein from the
introduced PVCP-PIP is produced in the transgenic plant or the virus
does not participate in heterologous encapsidation in nature.'' The
2004 SAP concluded that ``[t]his method can... be considered seriously
if deemed necessary'' (Ref. 25). However, the Agency concluded (as
discussed above in Unit III.D.1.ii.) that such methods are not
necessary because heterologous encapsidation is so rarely likely to be
of any significant ecological concern.
Based on these considerations, EPA presented a set of modified
conditions to the 2005 SAP that reflected the advice of the 2004 SAP.
Those conditions were the same as those that EPA is proposing today in
Sec. 174.27(b) except that Sec. 174.27(b)(2) as submitted to the 2005
SAP included an additional provision: this criterion could be met by
meeting the current conditions or by meeting the condition that ``the
properties of the viral pathotype that are determined by the coat
protein gene used to create the PVCP-PIP are substantially similar to
the properties of a viral pathotype that naturally infects plants in
the United States, and the viral pathotype used to create the PVCP-PIP
naturally infects plants of the same species as that containing the
PVCP-PIP.'' EPA is no longer proposing this condition as a means of
meeting Sec. 174.27(b) because the 2005 SAP concluded that it was
``unusable and cannot be re-written into a satisfactory form'' because
of the difficulty of defining ``properties'' and ``substantially
similar'' in this context (Ref. 11).
E. Production of Proteins
1. Scientific issues. In addition to weediness and viral
interactions, a third concern associated with PVCP-PIPs relates to the
potential production of proteins (called PVC-proteins) from the plant
virus coat protein sequences of the PVCP-PIP, i.e., the potential for
human or nontarget organism exposure to proteins that have not
previously existed in nature and thus should be examined to determine
whether they have potentially toxic or allergenic properties. EPA must
consider the safety of any potentially expressed proteins that are part
of the PIP when proposing
[[Page 19620]]
criteria to evaluate PVCP-PIPs for possible exemption.
EPA considered human dietary, human occupational, and nontarget
exposure risks in evaluating the safety of PVC-proteins for purposes of
this proposal as the Agency must do when evaluating whether a pesticide
can be exempt from the requirements of FIFRA. See EPA's assessment of
human dietary exposure risks and other non-occupational exposure risks
published in the companion document in today's Federal Register that
proposes to establish a tolerance exemption under FFDCA section 408 for
residues of the PVC-protein portion of a PVCP-PIP.
Many, if not all, of the considerations used to evaluate the
potential for novel occupational or nontarget exposures can be directly
extrapolated from the discussion in this companion document describing
EPA's base of experience with viruses infecting food plants. That
analysis led the Agency to draw three conclusions on which it is
relying to support the proposed tolerance exemption for residues of
PVC-proteins in food and which can also be used to support this
proposed criterion for exemption from FIFRA requirements. First, virus-
infected plants have always been a part of the human and domestic
animal food supply. Most crops are frequently infected with plant
viruses, and food from these crops has been and is being consumed
without adverse human or animal health effects. Second, plant viruses
are not infectious to humans, including children and infants, or to
other mammals. Third, plant virus coat proteins, while widespread in
food, have not been associated with toxic or allergenic effects to
animals or humans. EPA derived these conclusions from a sufficient
experience and information base to support the proposed tolerance
exemption and this proposed criterion for exemption from FIFRA
requirements.
EPA consulted the 2004 SAP about possible nontarget effects of PVC-
proteins and the validity of the Agency's risk assessment being based
on the known history of safe exposure to coat proteins of naturally
occurring plant viruses. Virus infected plants have always been a part
of the natural environment, and organisms that interact with plants
have likely been exposed to plant virus coat proteins over long periods
of time. The panel confirmed that PVC-proteins within the range of
natural variation of the virus would not be anticipated to present
risks to nontarget organisms, concluding that, ``[l]ethal effects in
animal life after feeding on PVCP-PIP plants are highly unlikely
because plant viruses are not known to have deleterious effects on
animal life. Additionally, animals routinely feed on non-engineered
virus-infected plants and do not die.... [S]ublethal effects are not
expected to be manifested in animal life, again because wildlife and
insects regularly feed on non-engineered virus-infected plants with no
apparent sublethal damage'' (Ref. 60).
The 2005 SAP echoed these general conclusions by pointing out that
virus coat proteins ``are naturally present in the environment and no
adverse effects to humans or non-targets have been reported'' (Ref.
11). However, the 2005 SAP also suggested that additional concerns
might warrant evaluation, including ``indirect ecological effects (such
as altered food sources, vegetative cover, or microbial communities)''
(Ref. 11). The particular concerns associated with such effects were
not articulated. PVC-proteins that meet the conditions of this
exemption are not expected to alter nontarget food sources because they
would be so similar to plant virus coat proteins that occur naturally.
Indirect effects such as changes in vegetative cover might occur if
crop plants containing a PVCP-PIP are larger and/or more productive in
the absence of virus infection relative to plants that are infected.
However, the overall effect on nontarget organisms is still likely to
be minor given that crops are often grown in the absence of viral
disease even without the use of a PVCP-PIP, and PVCP-PIPs exempted by
this proposal would have very limited ability to spread from crop
plants to wild or weedy relatives. PVCP-PIPs are not expected to impact
microbial communities because natural plant virus coat proteins are not
known to have any toxic mode of action. Moreover, plant virus coat
proteins already occur naturally in the environment so microbial
communities are already exposed to such proteins. Some Panel members
also ``expressed concern over potential effects on pollinators,'' but
EPA is unaware of any scientific evidence supporting this concern. EPA
concurs with other Panel members who believed that ``a history of
exposure by pollinators to naturally infected plants can be taken as
indicating that there are no novel risks'' (Ref. 11).
Other concerns raised by the 2005 SAP regarding nontarget and human
non-dietary exposure are addressed in the companion document published
in today's Federal Register, where they are discussed in the context of
consideration of the human dietary risks associated with PVC-proteins.
The companion document describes in Unit IV.C., for example, the basis
for EPA's conclusion that the hazard associated with PVC-proteins that
meet Sec. 174.27(c) of this proposed exemption is sufficiently low
that they do not rise to the level warranting regulation. These same
arguments can be applied to PVC-proteins that meet Sec. 174.27(c) in
this proposal, even in the rare cases when nontarget exposure to a PVC-
protein might be greater than the exposure to the corresponding natural
plant virus coat protein. The companion document also describes in Unit
IV.C. rationales that can be used to support EPA's conclusion that
nontarget exposure to PVC-proteins in plant tissues that do not
normally contain the corresponding plant virus coat protein is unlikely
to contribute significantly to risk. Nontarget organisms would be
exposed to natural plant virus coat proteins through a variety of
routes and there is no evidence that they would be toxic to any
nontarget organisms regardless of the route of exposure.
2. Proposed exemption criterion. As with the other proposed
criteria discussed in this document, EPA is proposing that Sec.
174.27(c) would have two parts: Section 174.27(c)(1) under which a
developer may self-determine if a PVCP-PIP meets the conditions, and
Sec. 174.27(c)(2) under which the Agency must make the determination.
i. Proposed categorical exemption criterion in Sec. 174.27(c)(1).
In developing the proposed categorical exemption for a subset of PVCP-
PIPs in which a developer could self-determine whether the criteria
were met, EPA sought to identify clearly those situations that pose low
risk with respect to protein production because any PVC-proteins
produced would be within the range of natural variation. EPA wants to
ensure that a long history of safe human and nontarget exposure has
occurred for any PVC-protein produced from a PVCP-PIP that could
qualify for this exemption. A PVCP-PIP would meet Sec. 174.27(c)(1) if
a product developer self-determines that:
The genetic material that encodes the pesticidal substance or
leads to the production of the pesticidal substance:
(i) Is inserted only in an inverted repeat orientation or
lacking an initiation codon for protein synthesis such that no PVC-
protein is produced in the plant, or
(ii) Encodes only a single virtually unmodified viral coat
protein. Multiple PVC-proteins could each separately meet this
criterion. Chimeric PVC-proteins do not qualify.
EPA intends with the phrase ``is inserted only in an inverted
repeat orientation or lacking an initiation codon for protein synthesis
such that no PVC-protein is produced in the plant''
[[Page 19621]]
to include only those PVCP-PIPs with the specified types of constructs
that the 2005 SAP indicated provide a high degree of certainty that no
PVC-protein would be produced. Although other types of constructs may
also usually not produce any PVC-protein, EPA believes it is necessary
to incorporate into its proposal a provision for an Agency review of
such constructs. In such a review, EPA could evaluate the level of
protein production, if any, that could occur under a variety of
circumstances and environmental conditions representative of those that
the plant may experience (see Unit III.E.2.ii.). EPA includes the word
``only'' and the phrase ``such that no PVC-protein is produced in the
plant'' in Sec. 174.27(c)(1)(i) to ensure that the proposed exemption
encompasses only those PVCP-PIPs that the 2005 SAP indicated ``could be
safely determined to have no [PVC-protein] expression regardless of
plant tissue, developmental stage, environmental conditions, or
exposure to virally-encoded suppressors of PTGS'' (Ref. 11). The
proposed exemption criterion in Sec. 174.27(c)(1)(i) would not be met
by a PVCP-PIP when there are multiple-copy insertions in the plant if
any of the copies is not in an inverted repeat orientation or lacking
an initiation codon for protein synthesis.
The Agency proposes to define the term ``unmodified'' to mean,
``having or coding for an amino acid sequence that is identical to an
entire coat protein of a naturally occurring plant virus. The Agency
proposes to define the term ``virtually unmodified'' to mean, ``having
or coding for an amino acid sequence that is identical to an entire
coat protein of a naturally occurring plant virus, except for the
addition of one or two amino acids at the N- and/or C-terminus other
than cysteine, asparagine, serine, and threonine and/or the deletion of
one or two amino acids at the N- and/or C-terminus.'' EPA's rationale
for these proposed definitions and alternative proposals for defining
``virtually unmodified'' are found in the companion document published
in today's Federal Register. The alternative proposals for virtually
unmodified will also be considered as alternatives under this FIFRA
proposal.
EPA is proposing to exclude more significantly modified PVC-
proteins from the proposed categorical exemption by requiring that the
genetic material encode ``only a single virtually unmodified viral coat
protein.'' For example, PVC-proteins containing internal insertions,
deletions, or amino acid substitutions would be excluded, as would be
chimeric proteins that are encoded by a sequence constructed from
portions of two or more different plant virus coat protein genes. EPA
is proposing to exclude such PVC-proteins from the self-determining
part of the exemption in response to the advice of the FIFRA SAP in
October 2004 that, ``[t]here was general agreement that an
allergenicity assessment\2\ would be appropriate for insertions or
deletions, except perhaps for terminal deletions that do not affect
overall protein structure.'' Insufficient information exists at this
time to allow EPA to describe a priori a criterion that would ensure
all PVC-proteins with modifications other than those encompassed by the
definition of ``virtually unmodified'' fall within the base of
experience supporting the proposed exemption. At this time, it is not
possible to make a categorical risk assessment finding that other types
of changes are unlikely to change the characteristics of any protein
produced. Thus, EPA proposes no other modifications be allowed in PVC-
proteins that would meet Sec. 174.27(c)(1).
---------------------------------------------------------------------------
\2\ The concern relating to the need for an allergenicity
assessment is relevant to the Agency's determinations concerning
occupational exposures.
---------------------------------------------------------------------------
EPA intends that multiple PVC-proteins expressed in the same plant
could each separately meet the criterion in Sec. 174.27(c)(1)(ii) but
that chimeric PVC-proteins could not meet this criterion. Chimeric
proteins would include PVC-proteins composed of the fusion of two (or
more) whole or partial capsid proteins, as well as chimeric proteins
that contain a PVC-protein fused with another, unrelated protein. The
2005 SAP concluded that such chimeric proteins could possibly have
``completely different antigenic and possibly allergenic properties
compared to the properties of the individual capsid proteins'' (Ref.
11). EPA is therefore unable to conclude that such proteins would be
low risk without a case-by-case review of the protein. EPA intends that
multiple, distinct PVC-proteins produced, for example, from a single
transgene insertion event or from multiple insertion events in the same
plant, could qualify for this exemption because the Agency believes
that the properties of each individual protein would be the relevant
factors to consider. Some members of the 2005 SAP believed that ``EPA
evaluations should consider effects of multiple constructs of PVCP-PIPs
introduced in transgenic plants'' (Ref. 11). The rationale for this
concern appears based in part on the potential for a synergistic effect
from multiple toxins. However, PVC-proteins produced from a PVCP-PIP
that could qualify for this exemption would not be expected to have any
toxic mode of action that could cause such a phenomenon. The rationale
for this concern appears to be also based in part on the potential for
multiple PVC-proteins to ``alter `natural' protein production in
plants'' (Ref. 11). However, EPA concurs with other 2005 SAP members
who ``believed that this situation was no different than is likely to
occur in nature, where a plant might be infected by multiple unrelated
viruses'' (Ref. 11). (See also Unit IV.E.1. in the companion document
published in today's Federal Register for the basis for EPA's
conclusion that exposure to plants with different levels of proteins
elicited by pathogen attack, wounding, or stress, i.e., ``pathogenesis-
related proteins,'' likely occurs normally.)
EPA believes the phrase ``an entire coat protein'' in the
definition of ``virtually unmodified'' conveys that segments of PVC-
proteins do not meet the criterion in Sec. 174.27(c)(1)(ii). This
limitation is based on the advice of the 2005 SAP that ``[d]etermining
whether PVC-proteins containing terminal deletions, or any other
modifications, are within the range of natural variation would require
the development of a database of the natural variation and truncated
forms of PVC-proteins that occur naturally.'' As such, EPA could more
appropriately take this consideration into account under the criterion
in Sec. 174.27(c)(2)(i) which contains provisions for an Agency review
(discussed below in Unit III.E.2.ii.). However, EPA is considering
several alternative definitions for ``virtually unmodified,'' some of
which may allow truncated PVC-proteins to meet the proposed criterion
in Sec. 174.27(c)(1)(ii). These alternatives are presented and
discussed in Unit IV.E.1. of the companion document published elsewhere
in today's Federal Register.
If the genetic material that encodes the pesticidal substance or
leads to the production of the pesticidal substance encodes only a
single virtually unmodified viral coat protein, no novel exposures to
humans or nontarget organisms are likely to occur because these PVC-
proteins are essentially identical to plant viral coat proteins that
are widespread in the plant kingdom, as most plants are susceptible to
infection by one or more viruses. EPA is relying on this history of
safe exposure to support this proposal. The Agency believes that when
such a PVCP-PIP is used, the PVCP-PIP would pose low probability of
risk with respect to protein production. EPA is proposing that no
further data or information would be needed to evaluate this issue
[[Page 19622]]
when Sec. 174.27(c)(1) is satisfied, and therefore no Agency review
would be necessary.
ii. Proposed exemption criterion conditional on Agency
determination in Sec. 174.27(c)(2). The Agency acknowledges that many
PVCP-PIPs may pose low risk with respect to concerns associated with
protein production even though they fail to satisfy Sec. 174.27(c)(1).
EPA is proposing to review such PVCP-PIPs under slightly different
factors that the Agency believes also ensure that qualifying PVCP-PIPs
pose low risk with respect to concerns associated with protein
production. Therefore, EPA is proposing that, under Sec. 174.27(c)(2),
a PVCP-PIP would also meet Sec. 174.27(c) if:
The Agency determines after review that the genetic material
that encodes the pesticidal substance or leads to the production of
the pesticidal substance:
(i) Encodes a protein that is minimally modified from a coat
protein from a virus that naturally infects plants, or
(ii) Produces no protein.
EPA developed the criterion in Sec. 174.27(c)(2) because the
Agency recognizes that developers may wish to modify PVCP-PIP
constructs to achieve certain product development goals such as greater
efficacy, and such modifications might result in changes to the
protein(s) produced. Most minor modifications to the genetic material
would be unlikely to cause changes to the protein that would be
significant from a human or nontarget organism perspective. Under Sec.
174.27(c)(2) EPA may consider such modifications on a case-by-case
basis. Many of the modifications are likely to produce proteins that
fall within the range of natural variation of the virus. However, it is
not currently possible to define clearly the range of variation of
viruses in general or even of any particular virus as discussed in Unit
IV.D. of the companion document published in today's Federal Register.
Therefore, Sec. 174.27(c)(2)(i) requires an Agency review to determine
qualification.
PVCP-PIPs are known to confer resistance by two mechanisms.
Resistance may be either protein-mediated, in which the level of
resistance is correlated with the level of protein expression, or it
may be RNA-mediated, in which the level of resistance is not correlated
with the level of protein expression. (See discussion in Unit II.E.) In
the case of RNA-mediated resistance, little to no PVC-protein may be
produced from the PVCP-PIP. In such cases, little to no risk due to
protein production would be associated with the PVCP-PIP. However, the
Agency believes that the only conditions that can a priori indicate
there will be no protein production are encompassed by the criterion in
Sec. 174.27(c)(1). Any other type of construct that may confer RNA-
mediated resistance through PTGS would be reviewed by the Agency under
the criterion in Sec. 174.27(c)(2)(ii). A PVCP-PIP would meet Sec.
174.27(c) if EPA determines that no PVC-protein is produced from the
PVCP-PIP.
If protein is produced, today's proposed exemption would cover only
those PVC-proteins that are not significantly different from naturally
occurring plant viral coat proteins, i.e., proteins that are virtually
unmodified or minimally modified. For more significantly modified PVC-
proteins, the base of experience upon which EPA relies for support of
the proposed exemption would not be applicable. Therefore, EPA would
not be able to make the determination a priori as part of this proposed
rule that the PVCP-PIP poses a low probability of risk to humans and
the environment and will not generally cause unreasonable adverse
effects on the environment even in the absence of regulatory oversight
under FIFRA. However, such PVCP-PIPs may still be eligible for
registration, and any significantly modified PVC-proteins could be
evaluated as part of the registration review (as discussed in Unit
II.G.). (For discussion of the concept of ``minimally modified'' see
Unit IV.E.2. of the companion proposed exemption published in today's
Federal Register.)
3. Historical approaches. EPA's current proposed approach is
consistent with what EPA has always intended. EPA has never intended
that any proposed exemption for PVCP-PIPs would cover those PIPs that
produce proteins significantly different from those that occur
naturally (November 23, 1994, 59 FR at 60524; July 19, 2001, 66 FR
37865 and 66 FR 37796).
IV. Proposed Exemption for Certain Inert Ingredients
As noted in Unit II.F. of this preamble, one of the general
qualifications for exemption at Sec. 174.21 is that ``any inert
ingredient that is part of the plant-incorporated protectant is on the
list codified at Sec. Sec. 174.485 through 174.490.'' EPA is proposing
to add several substances to Sec. 174.486 when they are used in a PIP
that is listed in 40 CFR part 174 subpart B - Exemptions and are in a
plant that satisfies Sec. 174.27(a):
beta-D-glucuronidase (GUS) from Escherichia coli and the
genetic material necessary for its production,
neomycin phosphotransferase II (NPTII) and the genetic
material necessary for its production,
phosphomannose isomerase (PMI) and the genetic material
necessary for its production,
CP4 enolpyruvylshikimate-3-phosphate (CP4 EPSPS) and the
genetic material necessary for its production,
glyphosate oxidoreductase (GOX or GOXv247) and the genetic
material necessary for its production, and
phosphinothricin acetyltransferase (PAT) and the genetic
material necessary for its production.
Below is a summary of EPA's finding that these inert ingredients
present a low risk to human health and the environment; the docket for
this proposed rule contains the Agency's full risk assessment in the
document ``Environmental Risk Assessment of Plant-Incorporated
Protectant (PIP) Inert Ingredients.'' EPA also proposes to add to
subpart X the partial tetracycline resistance gene as present under the
control of a bacterial promoter in papaya line 55-1.
EPA has conducted an environmental risk assessment of the PIP inert
ingredient phosphinothricin acetyltransferase (PAT) and the genetic
material necessary for its production. Topics covered in this
assessment include mode of action, ecological effects, endangered
species considerations, and gene flow from a modified plant to wild or
weedy relatives. Data cited in this assessment were submitted to the
Agency in support of Dekalb's DBT 418 and Ciba Seed's Event 176 Bt corn
registrations and Syngenta's COT 102 Bt cotton registration. Ecological
data and published information on the biology of this protein indicate
that this PIP inert ingredient is not known to be toxic and/or
pathogenic to plant or animal species. In 1997, the Agency granted a
tolerance exemption for this PIP inert ingredient in all plants due to
the low human health risks associated with this protein (40 CFR
180.1151; 62 FR 17717, April 11, 1997). Based on all of its
assessments, EPA has determined that this inert ingredient will pose
low ecological and occupational risk.
EPA has conducted an environmental risk assessment of the PIP inert
ingredient CP4 enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS)
and the genetic material necessary for its production. Topics covered
in this assessment include mode of action, ecological effects,
endangered species considerations, and gene flow from a modified crop
to wild or weedy relatives. Data cited in this assessment were
submitted to the Agency in
[[Page 19623]]
support of Monsanto's MON 810 Bt Corn registration. Ecological data and
published information on the biology of this protein indicate that this
PIP inert ingredient is not known to be toxic and/or pathogenic to
plant or animal species. In 1996, the Agency granted a tolerance
exemption for this PIP inert ingredient in all plants due to the low
human health risks associated with this protein (40 CFR 180.1174; 61 FR
40338, August 2, 1996). Based on all of its assessments, EPA has
determined that this inert ingredient will pose low ecological and
occupational risk.
EPA has conducted an environmental risk assessment of the PIP inert
ingredient glyphosate oxidoreductase (GOX) and the genetic material
necessary for its production. Topics covered in this assessment include
mode of action, ecological effects, endangered species considerations,
and gene flow from a modified crop to wild or weedy relatives. Data
cited in this assessment were submitted to the Agency in support of
Monsanto's MON 810 Bt Corn registration. Ecological data and published
information on the biology of this protein indicate that this PIP inert
ingredient is not known to be toxic and/or pathogenic to plant or
animal species. In 1997, the Agency granted a tolerance exemption for
this PIP inert ingredient in all plants due to the low human health
risks associated with this protein (40 CFR 180.1190; 62 FR 52505,
October 8, 1997). Based on all of its assessments, EPA has determined
that this inert ingredient will pose low ecological and occupational
risk.
EPA has conducted an environmental risk assessment of the PIP inert
ingredient neomycin phosphotransferase II (NPTII) and the genetic
material necessary for its production. Topics covered in this
assessment include mode of action, ecological effects, endangered
species considerations, and gene flow from a modified crop to wild or
weedy relatives. Data cited in this assessment were submitted to the
Agency in support of Monsanto's NewLeaf Potato and YieldGard Plus Corn
registrations and is discussed in more detail in the Bacillus
thuringiensis Plant-Incorporated Protectant and MON 863 Biopesticide
Registration Action Documents (Ref. 123). Ecological data and published
information on the biology of this protein indicate that this PIP inert
ingredient is not known to be toxic and/or pathogenic to plant or
animal species. In 1994, the Agency granted a tolerance exemption for
this PIP inert ingredient in all plants due to the low human health
risks associated with this protein (40 CFR 180.1134; 59 FR 49351,
September 28, 1994). Based on all of its assessments, EPA has
determined that this inert ingredient will pose low ecological and
occupational risk.
EPA has conducted an environmental risk assessment of the
Escherichia coli-derived PIP inert ingredient beta-D-glucuronidase
(GUS) and the genetic material necessary for its production. Topics
covered in this assessment include mode of action, ecological effects,
endangered species considerations, and gene flow from a modified crop
to wild or weedy relatives. Data cited in this assessment were
submitted to the Agency in support of Monsanto's Bollgard II Bt cotton
registration and are discussed in the Bollgard II Biopesticide
Registration Action Document (Ref. 124). Ecological data and published
information on the biology of this protein indicate that this PIP inert
ingredient is not known to be toxic and/or pathogenic to plant or
animal species. In 2001, the Agency granted a tolerance exemption for
this PIP inert ingredient in all plants due to the low human health
risks associated with this protein (40 CFR 180.1216; 66 FR 42957,
August 16, 2001). Based on all of its assessments, EPA has determined
that this inert ingredient will pose low ecological and occupational
risk.
EPA has conducted an environmental risk assessment of the
Escherichia coli-derived PIP inert ingredient phosphomannose isomerase
(PMI) and the genetic material necessary for its production. Topics
covered in this assessment include mode of action, ecological effects,
endangered species considerations, and gene flow from a modified crop
to wild or weedy relatives. Data cited in this assessment were
submitted to the Agency in support of Syngenta's MIR604 Bt corn
registration. Ecological data and published information on the biology
of this protein indicate that this PIP inert ingredient is not known to
be toxic and/or pathogenic to plant or animal species. In 2004, the
Agency granted a tolerance exemption for this PIP inert ingredient in
all plants due to the low human health risks associated with this
protein (40 CFR 180.1252; 69 FR 26770, May 14, 2004). Based on all of
its assessments, EPA has determined that this inert ingredient will
pose low ecological and occupational risk.
EPA believes the partial tetracycline resistance gene as present in
papaya line 55-1 presents low risk to human health and the environment
and could also be added to 40 CFR part 174 subpart X. No protein is
expected to be produced from the gene because it is under the control
of a prokaryotic promoter and is only a partial gene that is not
expected to function in plants (Ref. 125). Therefore, no ecological or
human health effects would be associated with this inert ingredient as
found in papaya line 55-1 because it consists of only DNA. Transfer of
an antibiotic resistance marker gene from plants to microorganisms in
the gut or in the environment may theoretically be possible, but it is
extremely unlikely (Refs. 126 and 127). In addition, because only a
portion of the tetracycline resistance gene is present in papaya line
55-1, if any horizontal gene transfer of this genetic material were to
occur, it would be unlikely to confer antibiotic resistance to any
organism that acquired it (Ref. 125).
EPA asked the 2005 SAP to comment on the Agency's environmental
risk assessment for the first six of these selectable markers. The
Panel concluded that the ``antibiotic resistance marker (NPTII) and
other markers (GUS and PMI) should be exempt provided they were in the
plant species determined to be of low risk using criteria'' the SAP
proposed as discussed in Unit III.C.2.i. (Ref. 11) and EPA relied on,
as appropriate, in developing the list comprising Sec. 174.27(a)(1).
In addition, the Panel concluded that the ``herbicide markers (CP4
EPSPS, GOX/GOXv247 and PAT) should not be exempted, but rather should
be considered on a case-by-case basis taking into consideration the
potential that the crop plant has to become feral'' (Ref. 11). EPA
notes, however, that the only crop plants that will be included on the
list comprising Sec. 174.27(a)(1) are those whose potential to become
feral has been considered. Thus, EPA's inclusion of these six
selectable markers in 40 CFR part 174 subpart X - List of Approved
Inert Ingredients when they are used in PIPs as inert ingredients in a
plant that satisfies Sec. 174.27(a) is consistent with the 2005 SAP's
recommendations regarding these inert ingredients.
EPA is also considering an alternative under which NPTII, GUS, and
PMI would be exempt from FIFRA when used as inert ingredients with any
exempt PIP, regardless of the plant in which they are expressed.
Although the SAP recommended that they only be exempt provided they
were used in a plant species determined to be of low risk based on the
considerations encompassed in Sec. 174.27(a), the Panel did not
provide a rationale as to why the markers would not be considered low
risk in other plants as well. Given that these markers are widespread
in the environment and would be expected to confer no particular
selective advantage
[[Page 19624]]
on any plant in the environment that might express them, the Agency
knows of no rationale why this limitation would be necessary. The
Agency believes that its risk assessment would support such an
exemption for these inert ingredients.
EPA is also proposing a technical correction to Sec. 174.480 to
make the language consistent with the general requirements for
exemption, which recognize that for some PIPs no FFDCA tolerance may be
required. In such cases, it is not necessary that the inert ingredients
have been exempted from FFDCA section 408 requirements.
V. Economic Analysis
Virus infection is a serious problem in agricultural production.
Virtually every plant species is susceptible to infection by at least
one of more than 500 known plant viruses (Ref. 6). Particular crop or
weed hosts are nearly always infected by certain plant viruses under
natural conditions (Ref. 103). Plant viruses create economic losses for
a vast variety of crops by reducing yields and negatively affecting the
quality of the crop, damaging fruits, leaves, seeds, flowers, stems,
and/or roots (Refs. 103 and 128). Symptom development and vector
transmission rates are affected by the environment and so can vary
across locations or seasons (Ref. 103).
Virus diseases have often resulted in devastating agricultural
losses, at times destroying entire plantings of crops in certain
locations (Ref. 103). For example, more than 100 million citrus trees
had been destroyed by citrus tristeza virus (CTV) by 1991 in citrus
growing regions around the world, including California (Ref. 129). CTV
is one of the most economically important viruses because of its
widespread distribution, the severity of damage caused by infection,
and the long life span of individual trees (Ref. 130).
Growers may need to use several control methods during a crop
season in an attempt to prevent viral infection and dissemination,
primarily by planting virus-free material for mechanically transmitted
viruses. For vector-transmitted viruses, control measures have often
focused on chemical insecticides, fungicides, and nematicides to reduce
the population of vectors that transmit viruses from plant to plant.
However, control of vectors is not always feasible or effective as a
way to control virus transmission (Ref. 103). In another common control
strategy, crops are grown in rotation with crops that the virus does
not infect to reduce the virus load in the field. This method has
serious limitations as well. In some cases, the development of
resistant cultivars can be the only viable means of virus control.
Plants developed through conventional breeding techniques offer some
degree of virus resistance. However, breeding for resistance has not
been successful for the majority of field crops that are severely
affected by viruses (Ref. 128). In some agricultural regions, some crop
species cannot be grown effectively because of the persistent presence
of infected plant populations and/or potential virus vectors (Ref.
103). Contrary to traditional control measures, transgenic virus-
resistant crops offer an effective means of virus protection.
This proposed rule would benefit the public by ensuring protection
of human health and the environment while also reducing the cost of and
time needed for regulatory review of transgenic virus-resistant crops.
This proposal would also help to appropriately allocate Federal
resources for risk evaluation by focusing Agency attention on those
PVCP-PIPs that warrant review. This proposed rule would also benefit
the industry by removing regulatory uncertainty for this class of
products.
This economic analysis (EA) prepared for this proposed rule
estimates the projected compliance cost for the industry under the
baseline of full registration for all PVCP-PIPs and compares that to
the compliance cost for the potentially affected industry under the
proposed rule in order to estimate the expected savings from the
regulation relief. The steps used to obtain a cost estimate for the
proposed rule are summarized below.
Since the nature and timing of future development of PVCP-PIPs are
unknown, the EA begins by identifying nine case studies that represent
the broadest range of PVCP-PIPs that the Agency anticipates could be
developed in the future. After considering the characteristics of the
products that have already been marketed, characteristics of the crop
plants that have been the subject of field trials for PVCP-PIPs, and
knowledge of the field of genetically engineered virus-resistant crops,
EPA estimated the percentage of products projected to be characterized
by each case study, i.e., the ``prevalence'' of the case study. The
stated prevalence represents the best estimate of the expectation of a
PVCP-PIP product like the one in a specific case study being developed
in the future.
For each case study, a set of data would be required of a developer
in order to register the PVCP-PIP. The cost and burden of potential
data requirements for each case study under the baseline are compared
with the potential data requirement costs and burden under the proposed
option. Using the prevalence for each case study, EPA estimated the
probability of developing a PVCP-PIP product like that examined in any
of the case studies in any year, given that the Agency anticipates 1.5-
2.5 PVCP-PIPs being developed each year over a 10-year period. These
probabilities determine the frequency and timing of development and
registration of PVCP-PIPs in a model EPA designed to compute compliance
cost savings.
To estimate compliance cost savings in any year, the number of
PVCP-PIPs like the one developed in a given case study was multiplied
by the difference between cost and burden under the proposed rule and
baseline. Since the model made use of probabilities, the average of
5,000 simulations was computed for each year to represent the annual
compliance cost savings for the proposed rule. Using this procedure,
the estimated annual impact, based on average cost estimates per data
requirement, is expected to result in a regulatory compliance cost
reduction approximately within the range of $340,000 and $360,000 a
year. Over a 10-year period, the annual average regulatory compliance
cost reduction is expected to be approximately $350,000.
The potential exemptions under the proposed rule, as compared to
the baseline under which no PVCP-PIPs are exempted, would reduce
regulatory costs for the potentially affected industry and the EPA,
remove regulatory uncertainty for industry, and provide important
information to the public regarding the safety of exempted PVCP-PIPs.
Entities that may benefit from the proposed rule and alternative
options are the public, companies that develop and market PVCP-PIPs
(applicants and/or registrants), farmers, and the environment. However,
potential future benefits to these entities are difficult to quantify
due to data limitations and uncertain market conditions. In addition,
considerable difficulty exists in quantitatively evaluating non-market
benefits, such as reduced environmental and human health risks,
consistency of regulation, reduced regulatory uncertainty, and
improvements in public perception of biotechnology products.
VI. Preliminary Statutory Finding
A. What Risk Assessment Methodology did EPA use for this Proposed Rule?
Generally, when EPA assesses the risks caused by the use of a
pesticide, it considers both the potential hazard that the pesticide
poses to the environment and the potential for
[[Page 19625]]
exposure to the pesticide due to its use. For most pesticides (e.g.,
chemical pesticides), EPA relies on data generated by laboratory
testing using representative animal models to estimate hazard
endpoints. To develop exposure estimates the Agency evaluates other
information including product characterization data, proposed use
patterns, and information generated from mathematical models. Exposure
and hazard estimates are combined to quantify the potential risk
associated with the pesticide's use. The data requirements describing
the types of information to be generated and other guidance for
assessing risk are detailed in 40 CFR part 158.
The questions posed as part of the risk assessment in evaluating
most pesticides (e.g., biological or chemical pesticides) can also be
posed for the PVCP-PIPs that are exempted in this proposed action, and
40 CFR part 158 can be used as guidance. EPA adopted an approach for
evaluating the potential risks of PVCP-PIPs that is consistent with the
unique characteristics of pesticides produced and used in a living
plant and the scientific knowledge and experience accumulated on these
substances.
To address the hazard endpoints described in 40 CFR part 158 for
the PVCP-PIPs that qualify for this proposed exemption, EPA relied on a
very large body of information in the public literature that was
developed through many decades of testing and observation. EPA thus did
not need to rely on animal model testing for assessing risk as it would
for most other pesticides (e.g., chemical pesticides) where specific
hazard data are lacking. In addition, PIPs are produced within the
living plant, and the pesticidal substance is used in situ in the
plant. Exposure to PVCP-PIPs is therefore limited relative to exposure
to chemical pesticides that are applied broadly in the environment,
e.g., through aerial application.
1. Large body of knowledge and experience exists. Typically, in
assessing a pesticide for environmental risk, EPA considers data
fulfilling the information requirements posed in 40 CFR part 158 to
evaluate the potential effect of the pesticide on birds, mammals,
freshwater fish and invertebrates, estuarine and marine animals, and
nontarget plants and insects (e.g., predators, parasites, and
pollinators). For most pesticides, this information must be generated
using animal models. To address these same questions for the PVCP-PIPs
that are the subject of this proposed exemption, EPA was able to rely
on a long history of hundreds, if not thousands of years of natural
exposure to plant virus coat proteins by nontarget organisms. EPA
relies on these experiences and the scientific literature generated by
a century of food safety studies (Refs. 131 and 132) to assess the
PVCP-PIPs that are the subject of these exemptions.
EPA also took into account the large and varied information base
available in the public scientific literature from a number of
disciplines including plant genetics, plant physiology, plant virology,
weed science, molecular biology, biochemistry, ecology, and plant
breeding. For example, the Agency used experimental data derived from
the science of plant pathology to characterize the pest resistance
mechanisms in plants (Ref. 56) and relied on the scientific knowledge
base of plant virology and virus ecology to evaluate how plant viruses
interact with each other and with the plant during infection (Ref. 60).
2. PVCP-PIPs are produced within the living plant, and the
pesticidal substance is used in situ in the plant, affecting the
exposure paradigm. EPA used information from the fields of plant
pathology, biochemistry, microbial ecology, and ecology in considering
all aspects of risk, including exposure. PVCP-PIPs are produced within
the living plant itself, and the pesticidal substance is used in situ
in the plant to protect against pests, in contrast to most other
pesticides, which must be applied to or near the plant. Because a PVCP-
PIP is produced and used within the plant, physiological constraints
limit the amount of pesticidal substance produced by the plant.
Regardless of the tissues containing the PVCP-PIP or the level at which
PVC-protein is expressed, the PVCP-PIP, including any PVC-protein, is
contained within the plant parts. Therefore, the routes by which other
organisms may be exposed to the PVCP-PIP may be more limited, e.g.,
dietary exposure is likely to be the predominant route of exposure, and
physical contact with the plant or plant parts will generally be
necessary for exposure to occur.
The PVCP-PIPs exempted by this proposed rule are biotic and are
subject to the processes of biodegradation and decay that all such
materials undergo (Ref. 133). Biotic materials are broken down to
constituent parts through the enzymatic processes of living organisms,
and these constituent parts are used as building blocks during growth
of other biotic substances. In addition, PVCP-PIPs are biodegradable to
their constituent elements through catabolism by living organisms.
Because of their biodegradable nature, PVCP-PIPs do not bioaccumulate
(i.e., build up in tissues because the body is unable to either break
the substance down or eliminate it) or biomagnify (i.e., progressively
build up in successive trophic levels because it bioaccumulates in the
bodies of organisms lower in the food chain). Because of these
characteristics, the potential for new exposures to occur beyond direct
physical exposures to the plant or plant parts is limited.
A question directly affecting the exposure component of the risk
assessment that has no equivalent in the assessment of more traditional
pesticides (e.g., chemical pesticides) must be posed for PIPs. Because
PIPs are produced and used in the living plant, the possibility that
the ability to produce a PIP may be transferred by outcrossing and
hybridization from the crop plant to a wild or weedy relative was
considered. A large volume of information is available in the public
literature to assess the risks of gene flow generally (Refs. 19 and
134) and for PVCP-PIPs in particular (Refs. 12, 32, 36, 135, 136, 137,
138, 139, and 140).
B. Exemption Determination for PVCP-PIPs, Including Certain Inert
Ingredients
EPA preliminarily concludes that PVCP-PIPs that meet the criteria
specified in this proposed action warrant exemption under FIFRA section
25(b)(2). The use of PVCP-PIPs that meet the criteria in 40 CFR 174.21,
including the criteria proposed in this Federal Register to be inserted
at 40 CFR 174.27 poses a low probability of risk to the environment and
is not likely to cause unreasonable adverse effects in the absence of
regulatory oversight. EPA bases this preliminary conclusion upon an
evaluation of the potential risks that use of PVCP-PIPs qualifying for
this exemption would reasonably pose to man and the environment, and
upon an evaluation of whether their use causes unreasonable adverse
effects. EPA preliminarily concludes that PVCP-PIPs qualifying for this
exemption pose a low probability of risk to the environment as
demonstrated by information from the fields of plant genetics, plant
physiology, plant virology, weed science, molecular biology,
biochemistry, ecology, and plant breeding; from many years of
experience growing and consuming plants that contain coat proteins from
plant viruses; and from Agency knowledge about horticultural and
agricultural practices. EPA also believes that use of these plant-
incorporated protectants in food is safe under the FFDCA section 408
standard as explained in the preamble
[[Page 19626]]
to this document and the companion document published elsewhere in this
issue of the Federal Register exempting residues of the PVC-protein
portion of a PVCP-PIP.
EPA believes that PVCP-PIPs that meet the criteria in 40 CFR
174.21, including the criteria proposed in this Federal Register to be
added at 40 CFR Sec. 174.27, are also not likely to cause unreasonable
adverse effects, even in the absence of regulatory oversight. As a
result, EPA concludes that PVCP-PIPs qualifying for this exemption do
not cause any unreasonable adverse effects with respect to human
dietary risk. Taking into account the economic, social, and
environmental costs and benefits of the use of such products, as
discussed in the preamble and associated Economic Analysis (found in
the docket for this rulemaking), EPA believes that the low levels of
risks that such products present do not justify the cost of regulating
such products. Note that products that qualify for this exemption would
remain subject to the requirement for submission of information
regarding adverse effects under 40 CFR 174.71. Even though EPA believes
the probability is very low that risks would arise with the PVCP-PIPs
qualifying for this exemption, the adverse effects reporting
requirement will alert the Agency should any such rare circumstances
occur. EPA could then address such instances, as appropriate, under
FIFRA.
VII. Request for Comment
EPA requests comment on whether the Agency has appropriately
identified in this proposed exemption those PVCP-PIPs that are of a
nature not requiring regulation under FIFRA. In particular, the Agency
requests comment on the following specific issues:
1. EPA requests comment on whether additional plants could be
appropriately included in the list of plants comprising proposed Sec.
174.27(a)(1) because they would present low risk with respect to
concerns associated with weediness of the plant itself and any wild or
weedy relatives of the plant if it were to contain any PVCP-PIP. For
example, the 2004 SAP identified the following plants that are not
included in proposed Sec. 174.27(a)(1): almond (Prunus communis),
apricot (Prunus armeniaca), cape daisy (Osteospermum spp.),
chrysanthemum (Dendranthema spp.), celery (Apium graveolens), eggplant
(Solanum melongena), geranium (Pelargonium spp.), hyacinth (Hyacinthus
spp.), guava (Psidium guajava), kiwi (Actinidia spp.), nectarine and
peach (Prunus persica), okra (Abelmoschus esculentus), olive (Olea
europaea), parsley (Petroselinum crispum), petunia (Petunia spp.),
pistachio (Pistacia vera), plum (Prunus domestica), spinach (Spinacia
oleracea), taro (Colocasia esculenta), tomato (Solanum lycopersicum),
watermelon (Citrullus lanatus), and wishbone flower (Torenia spp.).
EPA would be particularly interested in information about these
plants or others that addresses the questions in Unit III.C.2.i. that
EPA posed to crop experts as part of its evaluation as to whether
specific species should be included on the list. In some cases, EPA has
already consulted with one or more experts for these plants, but the
Agency does not believe it has the information necessary to draw a
conclusion for these plants. Given the reliance on expert opinion to
make these determinations, EPA would like to have responses from at
least three experts for any given crop before including it on the list
at Sec. 174.27(a)(1). In other cases, EPA completed at least three
consultations, but the Agency received information from at least one
expert suggesting that the plant may not meet the low risk standard for
inclusion in the Sec. 174.27(a)(1) list, e.g., because of questions
about the formation of viable hybrids in nature with wild or weedy
relatives or questions about the propensity of the crop to naturalize.
EPA describes its analyses in the following paragraphs and requests
assistance from the public on the issues raised.
EPA is inclined to include almond (Prunus communis) on the list in
Sec. 174.27(a)(1) on the basis of information received from expert
consultations. However, EPA is seeking any information from the public
that would enable the Agency to complete its assessment of the
potential for a PVCP-PIP to introgress into a population of a wild or
weedy relative or a naturalized population of the species and what
effect such introgression might have. Specifically, the experts
indicated that natural hybrids may be able to form with some other
stone fruit trees (Ref. 42). However, if such trees are likely to be
found in commercial cultivation, natural hybrids would not necessarily
be expected in areas outside of managed orchards. Regarding whether
almond is a weedy species, both experts mentioned that almond forms
feral populations. However, they have not usually required weed
management activity because ``the trees are infrequent and tend to be
seen as beneficial'' (Ref. 42). One expert said, ``Almond is not highly
susceptible to viruses affecting other Prunus tree crop species. Thus
virus resistance is not a major determinate of feral almond fitness in
current environments.... Thus, it is likely that transgenic resistance
would not greatly benefit either commercial or feral almonds'' (Ref.
42).
EPA is inclined to include amaryllis (Hippeastrum spp.) on the list
in Sec. 174.27(a)(1) on the basis of information received from
consultations with amaryllis experts that EPA conducted upon
recommendation from other experts in flower breeding. However, EPA is
seeking any information from the public that would enable the Agency to
complete its assessment of the weedy characteristics of amaryllis and
the potential for gene exchange between feral and cultivated
populations. Two experts indicated that there are no wild or weedy
relatives in the United States with which amaryllis can form viable
hybrids in nature, although one expert said, ``Hippeastrum puniceum
(Lam.) Kuntze is naturalized in Puerto Rico, the Virgin Islands,
Louisiana and Hawaii. Hippeastrum puniceum is a diploid species that is
occasionally used in breeding programs. In controlled crosses, it will
breed with other diploid species, and is probably represented in modern
Hippeastrum cultivars. However, most modern Hippeastrum cultivars
available in the florist and greenhouse trade are complex, tetraploid
hybrids that are difficult to backcross to H. puniceum'' (Ref. 42). One
expert believed that no species in the genus are known to become feral
or easily spread into non-crop areas. However, the others noted that
this occasionally occurs without requiring weed management activity.
One said, ``Hippeastrum puniceum may have been introduced into Puerto
Rico, possibly during pre-Colombian times, and it has since sparingly
naturalized.... Spread is slow and minimal and has not required
management activity'' (Ref. 42). Another said, ``Plants generally
naturalize in disturbed areas along roadsides and irrigation ditches.
The species is self-incompatible, but can form seed in naturalized
settings. The plants also reproduce asexually via off-sets. Long
distance dispersal appears minimal. Hippeastrum puniceum is considered
a low-risk introduced plant in Hawaii and appears that it does not
require active weed-management'' (Ref. 42). All three experts agreed
that it was unlikely acquisition of virus resistance would cause
amaryllis to become feral or easily spread into non-crop areas in the
United States. For example, one expert said, ``Hippeastrum has been
grown commercial outdoors since the early 1900's in semi-tropical areas
of the US (Hippeastrum is not winter-hardy).
[[Page 19627]]
There has not been a single record of any plants escaping and becoming
feral. There is no reason to believe that acquiring transgenic
resistance to one or more viruses would increase the ability of plants
to become feral or easily spread into non-crop areas'' (Ref. 42).
EPA is inclined to include apricot (Prunus armeniaca) on the list
in Sec. 174.27(a)(1) on the basis of information received from expert
consultations. However, EPA is seeking any information from the public
that would enable the Agency to complete its assessment of the
potential for a PVCP-PIP to introgress into a population of a wild or
weedy relative or a naturalized population of the species.
Specifically, two experts indicated that apricot may be able to cross
with plum species because ``[i]f planted in close proximity apricot can
be crossed by bees to Japanese plums. That suggests the same could
happen with native US plum species, of which there are many in the
eastern US'' (Ref. 42). However, both experts suggested that the
frequency of hybrid production would be extremely low. Two experts
indicated that apricot is not known to become feral or easily spread
into non-crop areas, while the third expert said that he has ``seen
rare plants in [Michigan] that are feral or left-over homeowner trees.
They did not appear to spread as the big seeds mostly drop under the
trees and seem not very competitive compared to the weeds'' (Ref. 42).
All of the experts agreed that acquisition of virus resistance would be
unlikely to change apricot's propensity to become feral. According to
one expert, ``It is not likely that this would occur because climatic
conditions and the occurrence of fungal and bacterial diseases are more
limiting than the viruses'' (Ref. 42).
EPA believes that more information about cape daisy (Osteospermum
spp.) is needed to address issues raised by expert consultation. EPA is
seeking any information from the public that would enable the Agency to
complete its assessment of the potential for a PVCP-PIP to enhance the
potential of species in this genus to naturalize. One expert indicated,
``Osteospermum fruticosum is a low-risk naturalized plant in Hawaii,
and is also found, along with O. ecklonis, in California. Other
Osteospermum species have naturalized in Australia and New Zealand. The
genus is endemic to the Cape Floristic Region of southern Africa which
has a Mediterranean climate. Thus, there is potential for more species
of Osteospermum to naturalize in California which, like Australia and
New Zealand, has a Mediterranean climate.... Transgenic or not,
Osteosperum [sic] has potential to further naturalize in Mediterranean
climates and needs further monitoring for invasive potential in these
areas'' (Ref. 42). However, the other two experts indicated that it was
unlikely that virus resistance would cause cape daisy to become feral
or easily spread into non-crop areas. One said, ``Other factors are
much more likely to limit its invasive potential, such as available
moisture, presence of competing vegetation, and predation by insects
and vertebrates. Viruses do not appear to be limiting its spread''
(Ref. 42). The other expert said, ``Viral resistance could conceivably
increase fecundity and spread, but there is no data to confirm or
refute the possibility'' (Ref. 42).
EPA is inclined to include chrysanthemum (Dendranthema spp.) on the
list in Sec. 174.27(a)(1) on the basis of information received from
consultations with two chrysanthemum experts. These experts indicated
that there are no wild or weedy relatives in the United States with
which commercial chrysanthemum can form viable hybrids in nature. One
expert believed that no species in the genus are known to become feral
or easily spread into non-crop areas, while the other noted that this
has occurred rarely in California, Ohio, Pennsylvania, and
Massachusetts. Nevertheless, these populations have not required weed
management activity because they ``have remained small consisting of
only a few plants'' (Ref. 42). Both experts believed it unlikely that
acquired virus resistance could lead to commercial chrysanthemum
becoming feral or easily spreading into non-crop areas. One expert
said, ``Plants in the genus Dendranthema are generally not easily
propagated by seed, and are vegatatively [sic] propagated by cuttings
or division. They do not compete well with other plants and do not
persist in untended garden situations, and would certainly not do so in
non-crop areas'' (Ref. 42).
EPA has received one response from an eggplant expert suggesting
that eggplant (Solanum melongena) meets the requirements for inclusion
on the list in Sec. 174.27(a)(1). This consultation indicates that
eggplant meets the three conditions outlined above by the SAP: it does
not have wild or weedy relatives in the United States with which it can
form viable hybrids in nature, it is not currently weedy or invasive in
the United States, and there is no reason to believe that acquisition
of virus resistance would make eggplant weedy or invasive. The expert
said, ``Similar to other species where wild relatives have been
utilized to enhance the cultivated form of the crop, genes for improved
fitness are derived from the wild relative. Neither the disease
resistant wild relative nor the improved cultivars have shown a
propensity to become feral'' (Ref. 42). EPA is seeking public comment
on this determination because the Agency desires a more robust response
base.
EPA believes that more information about geranium (Pelargonium
spp.) is needed to address issues raised by expert consultation. EPA is
seeking any information from the public that would enable the Agency to
complete its assessment of the potential for a PVCP-PIP to spread to a
wild or weedy population in the United States or enhance the potential
of species in this genus to naturalize. Regarding the potential for
spread to a wild or weedy population, two experts indicated that
species within this genus do not form viable hybrids in nature with
wild or weedy relatives in the United States, but a third expert said,
``In the wild, P. cucullatum will hybridize with P. betulinum (L.)
L'Her. and P. patulum Jacq. Pelargonium grandiflorum forms natural
hybrids with P. sublignosum Knuth. The extent to which these
hybridizations and other hybridizations occur is not well known'' (Ref.
42). Regarding the weedy tendencies of this genus, one expert indicated
that ``nine species are reported as naturalized or persistent in
California... but most occupy disturbed sites near cultivated or
urbanized areas'' (Ref. 42). Another expert said, ``It seems possible
that in Mediterranean climates Pelargonium could become a weed
problem'' (Ref. 42). Two other experts thought that acquisition of
virus resistance would not affect the weedy tendencies of this genus.
One said, ``Pelargonium species are notoriously poor seed producers and
are all also native to Africa, particularly South Africa. They have
specialized ecological niches that would not easily be available
anywhere in the U.S. or its territories. California is the most likely
place where this could happen, and no incidence of an adventive
Pelargonium has ever been reported. Viral resistance would not mitigate
these factors that prevent adventive establishment'' (Ref. 42).
EPA is inclined to include hyacinth (Hyacinthus spp.) on the list
in Sec. 174.27(a)(1) on the basis of information received from
consultations with hyacinth experts. However, EPA is seeking any
information from the public that would enable the Agency to complete
its assessment of the potential for hyacinth to naturalize. Three
experts consulted indicated that this genus does not form viable
hybrids in nature with
[[Page 19628]]
wild or weedy relatives in the United States. Two experts indicated
that there are no naturalized species of Hyacinthus in the United
States, although a third said, ``Hyacinthus orientalis has been
reported as naturalized in the Blackland Prairies of Texas,'' but
details were not available (Ref. 42). All three experts agreed that
acquired virus resistance is unlikely to make hyacinth become feral or
spread into non-crop areas.
On the basis of expert consultation, EPA has concluded that guava
(Psidium guajava) does not meet the low risk standard needed for
inclusion on the Sec. 174.27(a)(1) list. Two experts indicated that
more research is needed to establish the potential for outcrossing with
wild or weedy relatives. All three experts reported that guava is known
to become feral or easily spread into non-crop areas in the United
States. One expert stated, ``Guava is a vigorous, common, weed in both
warm to cool climates. It would likely give this plant additional
competitive advantage with transgenic resistance to viruses'' (Ref.
42). However, another expert believed that ``[g]uava is easily spread
without having transgenic resistance. It does not appear that
containing resistance to one or more virus [sic] would enhance its
ability to become feral'' (Ref. 42). EPA requests commenters who
believe guava would be appropriate to include on the list in Sec.
174.27(a)(1) specifically to address whether there are wild or weedy
relatives with which guava could form viable hybrids in nature in the
United States (including Puerto Rico, the Virgin Islands, Guam, the
Trust Territory of the Pacific Islands, and American Samoa) and to
address the concern that guava is a weedy species and acquisition of
virus resistance could exacerbate these tendencies. Please provide
literature citations or other evidence to support any claims contrary
to EPA's expert consultations.
EPA believes that more information about lily (Lilium spp.) is
needed to address issues raised by expert consultation conducted after
recommendation from other flower experts. EPA is seeking any
information from the public that would enable the Agency to complete
its assessment of the potential for lily to become feral or spread into
non-crop areas and the impact that acquired virus resistance might have
on this potential. The experts agreed that in the United States the
likelihood of a species in the genus Lilium forming viable hybrids in
nature with a wild or weedy relative was very small given that lilies
do not cross readily. ``This is especially true for the hybrids that
are adapted or selected for the intensive greenhouse or irrigated
gardens' environment. These lilies do not form successful colonies
outside these specific environments. The chance that genes will be
transferred from gardens to wild populations is negligible'' (Ref. 42).
However, regarding the weedy tendencies of this genus, one expert said
``Several species of Asian or European origin are sporadically
naturalized following escape from cultivation, but none strays far or
is widespread or common enough to be considered a pest.... Lilium
longiflorum (Easter lily; Japan) has been recorded from Utah and
Florida'' (Ref. 42). Another expert said, ``Lilium [formosanum] (Taiwan
lily) has been known to invade natural habitats in Northern and Eastern
Australia.... Caution would be advised in introducing L. [formosanum]
into... the US'' (Ref. 42). Two experts believed it unlikely that
acquired virus resistance would affect the likelihood of lilies
becoming feral, although a third said, ``Virus resistance might
increase the speed and degree with which these exotic species might
naturalize'' (Ref. 42).
EPA is inclined to include nectarine and peach (Prunus persica) on
the list in Sec. 174.27(a)(1) on the basis of information received
from expert consultations. However, EPA is seeking any information from
the public that would enable the Agency to complete its assessment of
the potential for a PVCP-PIP to introgress into a population of a wild
or weedy relative or a naturalized population of the species and what
effect such introgression might have. Specifically, the experts
indicated that natural hybrids may be able to form with some other
stone fruit trees (Ref. 42). However, if such trees are likely to be
found in commercial cultivation, natural hybrids would not necessarily
be expected in areas outside of managed orchards. Regarding whether
Prunus persica is a weedy species, three of the four experts mentioned
that nectarines and peaches are able to form feral populations (Ref.
42). Nevertheless, three of the four experts indicated that they
believed it would be unlikely that Prunus persica's weedy tendencies,
if any, would be exacerbated if it acquired transgenic resistance to
one or more viruses. One expert said, ``Generally the viruses are not
the limiting factor to the establishment of feral peaches. The limiting
factors are fungal and bacterial diseases that kill the plants before
they can reproduce'' (Ref. 42). The fourth expert said, ``I would
expect that the acquisition of virus resistance would enhance the
spread of feral populations but would suggest that other causes of
death, such as peach tree short life, bacterial canker and Armillaria
Root Rot, are likely to be a more significant limitation to the spread
and longevity of a feral nectarine tree'' (Ref. 42).
EPA believes that more information about olive (Olea europaea) is
needed to address issues raised during expert consultation. Two experts
indicated that hybridization with a wild or weedy relative has not been
documented in the United States (Ref. 42). Both of these experts
indicated that olive can naturalize. However, they disagreed about the
frequency with which this is likely to occur. One expert suggested
olive frequently forms reproducing and sustaining populations in non-
crop areas and that it was ``highly likely'' that olive would become
feral or easily spread into non-crop areas if it acquired transgenic
resistance to one or more viruses because ``O. europaea seeds are very
viable and dispersed by rodents'' (Ref. 42). However, another said,
``It is highly unlikely that olives would become strongly feral or
widely spread because the seeds are infrequently spread far from the
tree, have a low reproduction rate due to poor seed germination and
have a high rate of feral seedling mortality. Further, as a slow
growing tree olives do not spread rapidly'' (Ref. 42). The 2005 SAP
also commented on including olives in the list of plants in Sec.
174.27(a)(1). They noted olives have reportedly formed ``feral olive
infestations in the Channel Islands National Park, and in oak woodlands
and forest on Sonoma Valley and Davis, CA. In California, olive is
`considered an invasive exotic' that `compete[s] with native flora'
(personal communication)'' (Ref. 42). EPA believes that before olive
could be added to the list of plants in Sec. 174.27(a)(1), the Agency
would need information to resolve the question of how weedy olive is in
the United States and the effect virus resistance would have on any
feral populations of olive that could acquire a PVCP-PIP from
cultivated olive.
EPA has received one response from a parsley expert suggesting that
parsley (Petroselinum crispum) meets the requirements for inclusion on
the list in Sec. 174.27(a)(1). This consultation indicates that
parsley meets the three conditions outlined above by the SAP: it does
not have wild or weedy relatives in the United States with which it can
form viable hybrids in nature, it is not currently weedy or invasive in
the United States, and there is no reason to believe that acquisition
of virus resistance would make parsley weedy or invasive. The breeder
noted that parsley
[[Page 19629]]
could form viable hybrids with feral populations of parsley, but
``parsley populations are generally quite short-lived away from
cultivation and typically are not self-sustaining'' (Ref. 42). He also
noted, ``I would not expect parsley to become more easily spread with
the acquisition of virus resistance. Although I'm aware that parsley is
a host to celery mosaic virus and carrot motley dwarf, I have not known
these viruses to be common limiting factors in parsley growth or
reproduction, at least not here at our genebank in Iowa. Fungal
diseases and insects are much more important'' (Ref. 42). EPA is
seeking public comment on this determination because the Agency desires
a more robust response base.
EPA is inclined to include petunia (Petunia spp.) on the list in
Sec. 174.27(a)(1) on the basis of information received from
consultations with petunia experts. However, EPA is seeking any
information from the public that would enable the Agency to complete
its assessment of the weedy characteristics of petunia and the
likelihood that acquired virus resistance could cause petunia to become
feral or easily spread into non-crop areas. The experts indicated that
this genus does not form viable hybrids in nature with wild or weedy
relatives in the United States. However, two of the three experts
indicated that petunia has formed reproducing and sustaining
populations in non-crop areas while noting that such populations have
not required weed management activity. All three experts indicated that
acquired virus resistance is unlikely to change the status quo.
However, one noted that, ``as viruses affect petunia vigor, resistance
might conceivably increase the odds'' (Ref. 42).
EPA is inclined to include pistachio (Pistacia vera) on the list in
174.27(a)(1) on the basis of information received from two expert
consultations. However, EPA is seeking any information from the public
that would enable the Agency to complete its assessment of the
potential for a PVCP-PIP to introgress into a population of a wild or
weedy relative or a naturalized population of the species and what the
impact of acquired virus resistance is likely to be. Specifically, the
experts indicated several crosses have been reported in the literature,
suggesting ``that potentially P. vera genes can eventually be
transmitted to other species in the form of gene flow.'' However,
hybrids are only rarely formed as ``they are isolated
phenologically....'' Nevertheless, one expert also indicated, ``There
are a lot of unknowns in the phenology and cross-compatibility of
different species of pistachio'' (Ref. 42). Both experts indicated that
ferality in pistachio is rare. One suggested it was not possible to say
what the likelihood would be that pistachio would become feral or
easily spread into non-crop areas if it acquired transgenic virus
resistance. However the other said, ``It is very unlikely pistachio
would be widely feral as the primary method of spread, drop from the
tree, results in a large percentage (>95%) of the nuts degrading, so
they do not sprout. Further, the nuts do not go a long distance when
they drop, localizing spread if sprouting does occur. Finally, if birds
do remove a nut with a viable embryo from the tree they generally
destroy it by eating...'' (Ref. 42).
EPA is inclined to include plum (Prunus domestica) on the list in
Sec. 174.27(a)(1) on the basis of information received from expert
consultations. However, EPA is seeking any information from the public
that would enable the Agency to complete its assessment of the
potential for a PVCP-PIP to introgress into a population of a wild or
weedy relative or a naturalized population of the species.
Specifically, the experts indicated that several native plum species
occur in the United States. However, one indicated that because ``P.
domestica is a hexaploid, it would not cross with native Prunus plum
species, which are all diploid'' (Ref. 42). In addition, if any hybrids
between cultivated plum and wild American plum species did occur, they
``would not be fertile because of the chromosome number difference.''
EPA thus believes that the risk of introgressing a PVCP-PIP into a wild
or weedy population through gene transfer in the United States is very
low. Regarding whether plum is a weedy species, one expert mentioned
that although he had not personally observed it, he ``heard from others
that domestica... [is] found naturalized particularly in New England
and Oregon. Some of these species tend to be easily spread by root
suckers, and are better able to compete as weeds. Likely they only
survive on roadsides and unmanaged areas, and could be easily killed if
desired'' (Ref. 42). Nevertheless, all three of the experts indicated
that they believed it would be unlikely that plum's weedy tendencies,
if any, would be exacerbated if it acquired transgenic resistance to
one or more viruses. According to one expert, ``I doubt viruses are the
only thing which restricts domestica from spreading more than it
already has'' (Ref. 42). According to another, ``Currently virus
diseases are not the most important limiting diseases for plum in the
U.S. Other fungal and bacterial diseases are the limiting factors and
cause death of uncared for commercial plums. Therefore transgenic plums
with virus resistance would still be very susceptible to these limiting
fungal and bacterial diseases'' (Ref. 42).
EPA has received one response from a spinach expert suggesting that
spinach (Spinacia oleracea) meets the requirements for inclusion on the
list in Sec. 174.27(a)(1). This consultation indicated that spinach
meets the three conditions outlined above by the SAP: it does not have
wild or weedy relatives in the United States with which it can form
viable hybrids in nature, it is not currently weedy or invasive in the
United States, and there is no reason to believe that acquisition of
virus resistance would make spinach weedy or invasive. The expert
noted, ``Transgenic viral resistance alone probably would not make
spinach survive wild conditions, because there are other fungus (e.g.
downy mildew, Stemphylium leaf spot) diseases and bacterial diseases
(e.g. bacterial leaf spot), as well as drought resistance and competing
ability issues'' (Ref. 42). EPA is seeking public comment on this
determination because the Agency desires a more robust response base.
EPA believes that more information about taro (Colocasia esculenta)
is needed to address issues raised by expert consultation. For example,
although experts knew of no weedy relatives with which taro might
cross, ``crossing is theoretically possible among all of the taros''
(Ref. 42). One expert indicated that ``taro can flower naturally in
places such as Kula in Maui, Hawaii. The climate there allows taro to
flower naturally, whereas in other places it is often necessary to
induce flowering with hormone applications. Furthermore, hybrids made
by cross-fertilization are viable. It is entirely possible for taro to
survive in the wild in tropical and subtropical climates. Most taros
would succumb because taro has been cultivated for so long that it is
mostly dependent on humans to compete with many weeds. By itself it is
almost always out-competed by weeds and dies out. But theoretically it
can survive, it can cross-pollinate and form viable progeny'' (Ref.
42). Regarding whether taro is known to become feral or easily spread
in non-crop areas, one expert said, ``YES, but only in favorable
conditions of adequate warmth and moisture.'' Another expert indicated
that ``taro is considered an invasive species in certain places
(Florida)'' (Ref. 42). Regarding whether acquired transgenic resistance
to one or more viruses could change taro in this
[[Page 19630]]
respect, the experts disagreed. One expert said, ``It is highly
unlikely that taro with acquired transgenic resistance would spread to
non-crop areas because the probability of crossing is extremely small.
Through vegetative propagation it will require man intervention just as
non-transgenic plants.'' Another expert said, ``Taro has many pests,
including viruses, that restricts [sic] its ability to compete with
more weedy plant species. Resistance to any of these pests would
increase its competitiveness but this is not likely to turn taro into a
weed problem.'' However, the third expert said, ``With resistance to
one or more virus diseases, taro would become hardier. That is the
reason for breeders to go to the trouble of developing disease-
resistant plants. A hardier taro is more likely to be successful and
survive as an escaped cultivated species. It has already been seen that
taro has become feral in certain parts of Florida. With added
resistance, it would be more likely to survive in the wild, provided
that resistance gives it some advantage. In other words, if the virus
disease is important, resistance is valuable. In Thailand, the taro
plants that one can find along roadsides (feral) possess a high degree
of resistance to taro leaf blight, the most destructive disease of
cultivated taro there. Those that don't possess resistance don't stand
much of a chance to survive on their own'' (Ref. 42). EPA believes that
before taro could be added to the list of plants in Sec. 174.27(a)(1),
the Agency would need information to evaluate the likelihood that feral
populations of taro could acquire a PVCP-PIP from cultivated taro and
to evaluate whether acquisition of virus resistance is likely to
increase taro's likelihood of forming feral populations.
EPA believes that more information about tomato (Solanum
lycopersicum) is needed to address issues raised by several experts
that EPA consulted. For example, three of four experts indicated that
tomato is able to form viable hybrids in nature in the United States
with its putative progenitor Solanum lycopersicum var. cerasiforme.
These experts indicated the hybrids formed are fertile, self-
compatible, and freely intercross due to highly compatible phenology.
However, a third expert indicated that ``[a]lthough crosses can occur
between wild species and cultivated tomato, usually with human
intervention, the direction of the cross is such that the wild species
has to be the male parent.... If the cultivated tomato has the
transgene, transfer to wild species via pollen will not happen'' (Ref.
42). EPA is not however interested solely in whether transfer occurs
via pollen, but whether a transgene could introgress into a wild
population through a hybrid intermediate. Three of four experts also
indicated that tomato is able to form feral populations in the United
States (including Puerto Rico, the Virgin Islands, Guam, the Trust
Territory of the Pacific Islands, and American Samoa), although one
expert pointed out that neither virus-resistant cultivars nor resistant
wild relatives have demonstrated a greater propensity to become feral,
suggesting that acquisition of a PVCP-PIP may not exacerbate whatever
weedy tendencies exist in tomato. However, another expert suggested
that this question would have to be tested in the field under
controlled conditions. EPA believes that before tomato could be added
to the list of plants in Sec. 174.27(a)(1), the Agency would need
information to evaluate the effect of virus resistance on any wild or
weedy populations of tomato that could acquire a PVCP-PIP from
cultivated tomato and to evaluate whether acquisition of virus
resistance is likely to exacerbate tomato's weedy tendencies.
EPA believes that more information about watermelon (Citrullus
lanatus) is needed to address issues raised by expert consultation. For
example, experts indicated that watermelon is able to cross with C.
lanatus var. citroides. Moreover, one expert indicated hybrids made by
cross-fertilization are sexually fertile and demonstrate ``[m]ore vigor
compared with cultivated watermelon (C. lanatus var. lanatus)'' (Ref.
42). Regarding whether watermelon is known to become feral or easily
spread in non-crop areas, one expert indicated that escaped plants are
able to form reproducing and sustaining populations in non-crop areas,
although this occurs rarely and has not required weed management
activity outside of crop areas (Ref. 42). Regarding whether acquired
transgenic resistance to one or more viruses could change watermelon in
this respect, one expert indicated this was ``[u]nlikely. Watermelons
have few viruses that kill the plant or decrease its reproductive
activity. Therefore, gaining virus resistance will not likely increase
it's [sic] reproductive success in feral populations'' (Ref. 42).
Another expert said, ``Virus pressure would likely be far less in feral
populations than in cultivated fields due to differences in time of
germination, rate of growth, population density, [and] reduced numbers
of aphid vectors'' (Ref. 42). EPA believes that before watermelon could
be added to the list of plants in Sec. 174.27(a)(1), the Agency would
need information to evaluate the likelihood that wild populations of C.
lanatus var. citroides or feral populations of C. lanatus var. lanatus
could acquire a PVCP-PIP from cultivated watermelon and what effect
this acquisition might have.
EPA believes that more information about wishbone flower (Torenia
spp.) is needed to address issues raised by expert consultation. EPA is
seeking any information from the public that would enable the Agency to
complete its assessment of the potential for a PVCP-PIP to enhance the
potential of species in this genus to naturalize. All three experts
consulted indicated that Torenia species do not form viable hybrids in
nature with wild or weedy relatives in the United States. However, all
indicated that Torenia has naturalized in certain areas of the United
States. One expert said, ``Torenia fournieri has been reported to
naturalize by seed in Florida and Louisiana, but it is not clear to
what extent. I personally have observed re-seeding in garden settings.
Given the rising popularity of Torenia in American horticulture, there
is probable cause for concern in the deep south, California and Hawaii.
However, the species in cultivation are heat sensitive and moisture-
demanding, which would probably limit the extent to which they can
naturalize'' (Ref. 42). Expert consultations also suggest that not
enough information is known about the potential of virus resistance to
affect the plant's weedy tendencies. One expert said, ``I do not know
to what extent viruses impact Torenia fournieri. It is conceivable that
viral resistance could increase fecundity'' (Ref. 42).
EPA is not proposing to include celery (Apium graveolens), kiwi
(Actinidia spp.), or okra (Abelmoschus esculentus) on the list in Sec.
174.27(a) because the Agency was unable to complete any expert
consultations on these crops. EPA is therefore seeking information from
the public to address whether such crops could qualify for inclusion on
the list.
EPA also requests comment on the weediness potential of squash
(Cucurbita pepo) and any wild or weedy relatives in the United States
that could acquire a PVCP-PIP from cultivated squash through gene flow.
2. EPA requests comment on the Agency's options for the weediness
criterion in Sec. 174.27(a)(2) discussed in Unit III.C.2.iii.
Specifically, the Agency is considering whether it is more appropriate
to evaluate the potential for a crop to form ``viable hybrids'' or
[[Page 19631]]
``viable, fertile hybrids'' in nature with a wild or weedy relative.
In addition, EPA is considering whether it is necessary to evaluate
whether the plant containing the PIP is unlikely to establish weedy or
invasive populations outside of agricultural fields in the United
States even if the plant contains a PVCP-PIP, assuming that the plant
has no wild or weedy relatives in the United States with which it can
form viable hybrids in nature and it is not a weedy or invasive species
outside of agricultural fields in the United States.
EPA also requests comment on language for the criterion in Sec.
174.27(a)(2) (e.g., such as under option four) that would allow EPA to
broadly consider the effect that virus resistance might have on wild or
weedy plant populations that could acquire the PVCP-PIP. Under such an
approach, the individual determinations that the Agency would make
would likely require data to be generated that would not normally occur
as a routine part of product development (but may be developed for a
review by USDA/APHIS). Such determinations are likely to involve
similar amounts of effort as registration reviews, but they would
provide a means whereby a PVCP-PIP could be exempted even if used in a
plant that has wild or weedy relatives in the United States. The Agency
requests commenters to indicate how controversial individual
determinations using such language as under option 4 are likely to be,
as the Agency would like to have an exemption procedure that requires
only one public notice (see Unit III.A.2.).
3. EPA requests comment on the merits of incorporating the use of
biocontainment and/or bioconfinement techniques into Sec. 174.27(a),
such that PVCP-PIPs deployed in tandem with such technology could be
determined to meet the weediness criterion. Please see the discussion
of this option in Unit III.C.3., which articulates several issues
associated with such an option and suggests regulatory language that
might be used.
4. EPA requests comment on the Agency's use of the term ``weedy.''
EPA uses the term in two different contexts: in ``wild or weedy
relatives'' and in ``weedy or invasive species.'' However, the Agency
notes that the term has a different meaning in each context. When
discussing a ``wild or weedy relative,'' EPA considers weedy plants to
be those with the characteristics of weeds, i.e., those that are
considered undesirable, unattractive, or troublesome, especially when
growing where they are not wanted. However, when discussing ``weedy or
invasive species,'' EPA considers a weedy species to be a species that
is an aggressive competitor in natural ecosystems. EPA recognizes that
it would be better to have a single definition of the term ``weedy,''
but the Agency believes both meanings of the term ``weedy'' are in
common, scientific usage. In addition, the Agency is not aware of a
term other than ``wild or weedy relative'' that would encompass all
plants that grow outside of agricultural fields, or a term other than
``weedy or invasive species'' that would encompass all of the plants
that are problematic from a management perspective. EPA would be
particularly interested in alternative suggestions to describe each of
these situations and thus enable the Agency to avoid using two
different meanings for the word ``weedy.''
5. EPA requests comment on whether the viral interactions criterion
in Sec. 174.27(b)(1)(i) could be expanded to read ``the viral
pathotype used to create the PVCP-PIP has naturally infected plants in
the United States or other parts of North America and naturally infects
plants of the same species as those containing the PVCP-PIP.'' EPA
recognizes that viruses are likely to move freely across political
boundaries. Thus, limiting this criterion to viruses that have
naturally infected plants ``in the United States or other parts of
North America'' may be most appropriate limitation for avoiding the
introduction of sequences from an exotic virus into the United States
through creation of a PVCP-PIP.
6. EPA requests comment on whether it is necessary for the Agency
to address viral interactions, i.e., recombination, as articulated in
Sec. 174.27(b), in order for the Agency to conclude that a PVCP-PIP is
low risk. EPA requests commenters to indicate whether their comments
apply to RNA viruses, DNA viruses, or both. The Agency notes that a
large number of PVCP-PIPs are likely to meet Sec. 174.27(b) as
proposed. EPA therefore requests commenters who believe Sec. 174.27(b)
is unnecessary to focus their remarks on why those PVCP-PIPs that do
not meet the conditions of proposed Sec. 174.27(b) would pose low risk
with respect to recombination rather than addressing the average risk
associated with PVCP-PIPs as a whole.
For the PVCP-PIPs that would only qualify for an exemption without
the limitations provided by Sec. 174.27(b), EPA does not believe the
Agency can conclude low risk with respect to recombination (as the
Agency must do in order to remove Sec. 174.27(b) entirely) because the
2004 and 2005 SAPs have identified specific instances where this
general conclusion may not hold. Nevertheless, EPA is considering
removing this criterion in whole or in part if the Agency receives
information suggesting that such factors as articulated and as
incorporated into Sec. 174.27(b) are unnecessary for concluding a
particular PVCP-PIP is low risk. For example, the Agency notes that the
current global movement of goods and people likely results in the at
least occasional transport of plant viruses great distances from their
original geographic distribution in spite of governmental efforts to
limit their movement. In such a context, the Agency questions the
relevance of requiring as a condition of exemption that the viral
pathotype used to create the PVCP-PIP has naturally infected plants in
the United States.
7. EPA requests comment on whether the protein production criterion
in Sec. 174.27(c)(1)(i) could be modified to encompass other types of
PVCP-PIP constructs that mediate resistance based on PTGS. According to
today's proposal, any such constructs other than those inserted only in
an inverted repeat orientation or lacking a start codon would be
reviewed by the Agency for lack of protein production under Sec.
174.27(c)(2). However, if the Agency could identify additional types of
constructs that would present reasonable assurance that no protein
would be produced in any plant tissues at any point in the plant's
developmental cycle, including if PTGS were to be suppressed, such
constructs could be included under Sec. 174.27(c)(1)(i) and would not
require Agency review to verify that no protein would be produced.
8. EPA requests comment on whether the Agency could extend the
proposed exemption (including regulatory text and rationale as written)
to other PIPs that are based on any plant virus gene that confers virus
resistance when no protein is produced from the inserted virus sequence
because it is inserted only in an inverted repeat orientation and/or it
lacks an initiation codon for protein synthesis. The 2005 SAP noted
that ``[o]ther PIPs conferring virus resistance should be evaluated
similarly as are the PVCP-PIPs, if the PIPs mode of action is via
PTGS'' (Ref. 11). However, the Panel also mentioned several risk
concerns associated with specific virus proteins. The Agency therefore
concluded that PTGS was a necessary but not sufficient condition for
expanding the exemption to other types of virus gene-based PIPs given
that protein can be produced under certain circumstances from many
constructs
[[Page 19632]]
that employ PTGS, and the Agency does not currently have sufficient
information to conclude that such protein would pose low risk to the
environment. In the case of the two types of inserts described above,
the 2005 SAP indicated that it could be ``safely determined'' that no
protein would ever be produced from such constructs (Ref. 11), and they
would meet Sec. 174.27(b) and (c). Section 174.27(a) would be
evaluated as it is evaluated for PVCP-PIPs given that the relevant
consideration would be the virus-resistant phenotype of the plant
rather than the means by which the trait is conferred. EPA thus
believes that the criteria in today's proposed exemption address all
relevant risk considerations for PIPs based on any plant virus gene
when no protein is produced from the inserted virus sequence. EPA is
therefore inclined to expand the exemption to include PIPs based on any
viral gene that confers virus resistance if the PIP meets Sec.
174.27(a) and no protein is produced from the inserted virus sequence
because it is inserted only in an inverted repeat orientation and/or it
lacks an initiation codon for protein synthesis.
9. EPA requests comment on the alternative approach the Agency is
considering for exempting marker genes that are used as inert
ingredients with PIPs under which NPTII, GUS, and PMI would be exempt
from FIFRA when used as inert ingredients with any exempt PIP,
regardless of the plant in which they are expressed (as discussed in
Unit IV).
10. EPA requests comment on the possibility of developing an
Agency-determined approach for exempting inert ingredients under FIFRA.
Under this approach, EPA would propose new language at 40 CFR 174.21(c)
that would enable the Agency to review inert ingredients on a case-by-
case basis to determine whether they meet the standard established for
inert ingredients in 40 CFR part 174 subpart X-List of Approved Inert
Ingredients. EPA is considering such a procedure to ensure that a low-
risk PVCP-PIP that otherwise meets the conditions for exemption at
Sec. 174.21 would not require a FIFRA registration solely due to the
presence of an inert ingredient that may prove to be low risk upon
review. The only alternative to registration for such a PVCP-PIP would
be to add the inert ingredient to the list through rulemaking under
FIFRA section 25(b), such that the PVCP-PIP could be exempted.
Rulemaking would take considerably longer than an Agency determination
procedure like that described in today's proposal for other exemption
criteria.
The criteria that EPA is considering for determining whether an
inert ingredient would be exempt under an Agency determination are:
i. The inert ingredient is non-toxic to humans and animals and does
not produce a toxic substance,
ii. The inert ingredient is non-allergenic, and
iii. If the inert ingredient is an antibiotic resistance gene or
marker protein, therapy with antibiotics would not be compromised even
if the gene were to be transferred from plants to microorganisms in the
gut of man or animal, or in the environment.
11. EPA requests comment on the Agency's assumption in the economic
analysis for this proposed rule that the estimated number of PVCP-PIPs
submitted for regulatory review will be the same per year over the next
10 years. EPA assumed a uniform distribution given that the Agency
lacks reliable information on which to base a more complex distribution
pattern. EPA is particularly interested in any data or information
supporting a different assumption for the economic analysis.
12. EPA requests comment on the usefulness of a guidance document
that would provide a simplified description of the final rule. EPA
intends to develop such a document and is interested to know what
specific content the public would find most helpful.
VIII. References
The following books, articles, and reports were used in preparing
this proposed rule and are cited in this document by the number
indicated.
1. Callaway, A., Giesman-Cookmeyer, D., Gillock, E.T., Sit, T.L.,
Lommel, S.A. The multifunctional capsid proteins of plant RNA viruses.
Annual Review of Phytopathology 2001; 39:419-60.
2. Kaniewski, W.K., Lawson, C. Coat protein and replicase-mediated
resistance to plant viruses. In: Hadidi, A., Khetarpal, R.K.,
Koganezawa, H. Plant Virus Disease Control. St. Paul, Minnesota: APS
Press, 1998:65-78.
3. Powell, P.A., Sanders, P.R., Tumer, N., Fraley, R.T., Beachy,
R.N. Protection against tobacco mosaic virus infection in transgenic
plants requires accumulation of coat protein rather than coat protein
RNA sequences. Virology 1990; 175:124-30.
4. Goldbach, R., Bucher, E., Prins, M. Resistance mechanisms to
plant viruses: an overview. Virus Research 2003; 92:207-12.
5. Savenkov, E.I., Valkonen, J.P.T. Silencing of a viral RNA
silencing suppressor in transgenic plants. Journal of General Virology
2002; 83:2325-35.
6. Waterhouse, P.M., Wang, M.B., Lough, T. Gene silencing as an
adaptive defence against viruses. Nature 2001; 411:834-42.
7. Kooter, J.M., Matzke, M.A., Meyer, P. Listening to the silent
genes: transgene silencing, gene regulation and pathogen control.
Trends in Plant Science 1999; 4:340-7.
8. Hamilton, A.J., Baulcombe, D.C. A species of small antisense RNA
in posttranscriptional gene silencing in plants. Science 1999; 286:950-
2.
9. Lu, R., Martin-Hernandez, A.M., Peart, J.R., Malcuit, I.,
Baulcombe, D. Virus-induced gene silencing in plants. Methods 2003;
30:296-303.
10. National Research Council. Genetically Modified Pest-Protected
Plants: Science and Regulation. Washington, DC: National Academy Press,
2000.
11. FIFRA Scientific Advisory Panel. Minutes of the December 6-8,
2005 Meeting on Plant-Incorporated Protectants Based on Virus Coat
Protein Genes: Science Issues Associated with the Proposed Rule. 2005.
12. Bartsch, D., Schmidt, M., Pohl-Orf, M., Haag, C., Schuphan, I.
Competitiveness of transgenic sugar beet resistant to beet necrotic
yellow vein virus and potential impact on wild beet populations.
Molecular Ecology 1996; 5:199.
13. National Research Council. Field Testing Genetically Modified
Organisms. Washington, DC: National Academy Press, 1989.
14. Keeler, K.H. Can genetically engineered crops become weeds?
Bio/Technology 1989; 7:1134-9.
15. National Research Council. Environmental Effects of Transgenic
Plants: The Scope and Adequacy of Regulation. Washington, DC: National
Academy Press, 2002.
16. Wennstrom, A. Risk assessment of genetically modified
undomesticated plants. In: den Nijs, H.C.M., Bartsch, D., Sweet, J.
Introgression from Genetically Modified Plants. Cambridge, MA: CABI
Publishing, 2004:297-307.
17. Levin, D.A. The origin of isolating mechanisms in flowering
plants. Evolutionary Biology 1978; 11:185-317.
18. Ellstrand, N.C., Prentice, H.C., Hancock, J.F. Gene flow and
introgression from domesticated plants into their wild relatives.
Annual Review of Ecology and Systematics 1999; 30:539-63.
19. Ellstrand, N. Dangerous Liaisons. Baltimore: Johns Hopkins
University Press, 2003.
20. Khetarpal, R.K., Maisonneuve, B., Maury, Y., Chalhoub, B.,
Dinant, S.,
[[Page 19633]]
Lecoq, H. et al. Breeding for resistance to plant viruses. In: Hadidi,
A., Khetarpal, R.K., Koganezawa, H. Plant Virus Disease Control. St.
Paul: APS Press, 1998:14-32.
21. MacClement, W.D., Richards, M.G. Virus in wild plants. Canadian
Journal of Botany 1956; 34:793-9.
22. Barnett, O.W., Gibson, P.B. Identification and prevalence of
white clover viruses and the resistance of Trifolium species to these
viruses. Crop Science 1975; 15:32-7.
23. Hammond, J. Viruses occurring in Plantago species in England.
Plant Pathology 1981; 30:237-44.
24. Raybould, A.F., Maskell, L.C., Edwards, M.L., Cooper, J.I.,
Gray, A.J. The prevalence and spatial distribution of viruses in
natural populations of Brassica oleracea. New Phytologist 1999;
141:265.
25. FIFRA Scientific Advisory Panel. Minutes of the October 13-15,
2004 Meeting on Issues Associated with Deployment of a Type of Plant-
Incorporated Protectant (PIP), Specifically those Based on Plant Viral
Coat Proteins (PVCP-PIPs). 2004.
26. Duffus, J.E. Role of weeds in the incidence of virus diseases.
Annual Review of Phytopathology 1971; 9:319-40.
27. Yahara, T., Oyama, K. Effects of virus infection on demographic
traits of an agamospermous population of Eupatorium chinense
(Asteraceae). Oecologia 1993; 96:310-5.
28. Funayama, S., Hikosaka, K., Yahara, T. Effects of virus
infection and growth irradiance on fitness components and
photosynthetic properties of Eupatorium makinoi (Compositae). American
Journal of Botany 1997; 84:823-30.
29. Friess, N., Maillet, J. Influence of cucumber mosaic virus
infection on the intraspecific competitive ability and fitness of
purslane (Portulaca oleracea). New Phytologist 1996; 132:103-11.
30. Maskell, L.C., Raybould, A.F., Cooper, J.I., Edwards, M.L.,
Gray, A.J. Effects of turnip mosaic virus and turnip yellow mosaic
virus on the survival, growth and reproduction of wild cabbage
(Brassica oleracea). Annals of Applied Biology 1999; 135:401-7.
31. Gilbert, G.S. Evolutionary ecology of plant diseases in natural
ecosystems. Annual Review of Phytopathology 2002; 40:13-43.
32. Fuchs, M., Chirco, E.M., McFerson, J.R., Gonsalves, D.
Comparative fitness of a wild squash species and three generations of
hybrids between wild x virus-resistant transgenic squash. Environmental
Biosafety Research 2004; 3:17-28.
33. Sukopp, U., Pohl, M., Driessen, S., Bartsch, D. Feral beets--
with help from the maritime wild? In: Gressel, J. Crop Ferality and
Volunteerism. Boca Raton: CRC Press, 2005:45-57.
34. Jones, R.A.C., Nicholas, D.A. Impact of an insidious virus
disease in the legume component on the species balance within self-
regenerating annual pasture. The Journal of Agricultural Science 1998;
131:155-70.
35. Funayama, S., Terashima, I., Yahara, T. Effects of virus
infection and light environment on population dynamics of Eupatorium
makinoi (Asteraceae). American Journal of Botany 2001; 88:616-22.
36. Power, A.G. Ecological risks of transgenic virus-resistant
crops. In: Letourneau, D.K., Burrows, B.E. Genetically Engineered
Organisms: Assessing Environmental and Human Health Effects. Boca
Raton: CRC Press, 2002:125-42.
37. Pilson, D., Prendeville, H.R. Ecological effects of transgenic
crops and the escape of transgenes into wild populations. Annual Review
of Ecology and Systematics 2004; 35:149-74.
38. Mitchell, C.E., Power, A.G. Release of invasive plants from
fungal and viral pathogens. Nature 2003; 421:625-7.
39. Colautti, R.I., Ricciardi, A., Grigorovich, I.A., MacIsaac,
H.J. Is invasion success explained by the enemy release hypothesis?
Ecology Letters 2004; 7:721-33.
40. Remold, S.K. Unapparent virus infection and host fitness in
three weedy grass species. Journal of Ecology 2002; 90:967.
41. Gibbs, A. A plant virus that partially protects its wild legume
host against herbivores. Intervirology 1980; 13:42-7.
42. U.S. Environmental Protection Agency. Compilation of Expert
Consultations on Weediness Concerns Associated with Plants that may
Contain a PVCP-PIP; docket control number EPA-HQ-OPP-2006-0642. 2006.
43. Ritala, A., Nuutila, A.M., Aikasalo, R., Kauppinen, V.,
Tammisola, J. Measuring gene flow in the cultivation of transgenic
barley. Crop Science 2002; 42:278-85.
44. U.S. Environmental Protection Agency. Biopesticides
Registration Action Document (BRAD) - Bacillus thuringiensis Plant-
Incorporated Protectants. http://www.epa.gov/pesticides/biopesticides/pips/bt--brad.htm. 2001.
45. OECD Environment Directorate. Consensus document on the biology
of Zea mays subsp. mays (maize). http://www.olis.oecd.org/olis/
2003doc.nsf/43bb6130e5e86e5fc12569fa005d004c/
f70b80eb7cd25728c1256d57003e5f0c/$FILE/JT00147699.PDF. 2003.
46. United States Department of Agriculture Animal and Plant Health
Inspection Service. USDA-APHIS Response to Cornell University and the
University of Hawaii Petition 96-051-01p for a Determination of
Nonregulated Status for `Sunset' Papaya Lines 55-1 and 63-1.
47. Chan, Y.K., Coppens d'Eeckenbrugge, G., Sanewski, G.M. Breeding
and variety improvement. In: Bartholomew, D.P., Paull, R.E., Rohrbach,
K.G. The Pineapple: Botany, Cultivation and Utilization. Oxon, UK: CABI
Publishing, 2003:33-55.
48. OECD Environment Directorate. Consensus document on the biology
of Solanum tuberosum subsp. tuberosum (potato). http://www.oecd.org/dataoecd/25/62/27854542.pdf. 1997.
49. United States Department of Agriculture Animal and Plant Health
Inspection Service. USDA/APHIS Petition 94-257 for Determination of
Nonregulated Status for Colorado Potato Beetle-Resistant Potato Lines
BT6, BT10, BT12, BT16, BT17, BT18, and BT23. 1995.
50. OECD Environment Directorate. Consensus document on the biology
of Glycine max (L.) Merr. (soybean). http://www.olis.oecd.org/olis/
2000doc.nsf/4f7adc214b91a685c12569fa005d0ee7/
c125692700623b74c1256996003e87fc/$FILE/00085953.PDF. 2000.
51. Haygood, R., Ives, A.R., Andow, D.A. Population genetics of
transgene containment. Ecology Letters 2004; 7:213-20.
52. Barton, N.H. The effects of linkage and density-dependent
regulation on gene flow. Heredity 1986; 57:415-26.
53. National Research Council. Biological Confinement of
Genetically Engineered Organisms. Washington, DC: National Academies
Press, 2004.
54. Al-Ahmad, H., Galili, S., Gressel, J. Poor competitive fitness
of transgenically mitigated tobacco in competition with the wild type
in a replacement series. Planta 2005; 222:372-85.
55. Gressel, J., Al-Ahmad, H. Assessing and managing biological
risks of plants used for bioremediation, including risks of transgene
flow. Zeitschrift f[uuml]r Naturforschung.C, A journal of biosciences
2005; 60:154-65.
56. Hull, R. Matthews' Plant Virology, Fourth ed. San Diego:
Academic Press, 2002.
57. Hammond, J., Lecoq, H., Raccah, B. Epidemiological risks from
mixed virus infections and transgenic plants expressing viral genes.
Advances in Virus Research 1999; 54:189-314.
[[Page 19634]]
58. Falk, B.W., Bruening, G. Will transgenic crops generate new
viruses and new diseases? Science 1994; 263:1395-6.
59. de Zoeton, G.A. Risk assessment: Do we let history repeat
itself? Phytopathology 1991; 81:585-6.
60. U.S. Environmental Protection Agency. Viral Interactions in
Viral Coat Protein Transgenic Plants: A Literature Review. 2004.
Washington, DC, Office of Science Coordination and Policy, Office for
Prevention, Pesticides and Toxic Substances.
61. Fraile, A., Alonso-Prados, J.L., Aranda, M.A., Bernal, J.J.,
Malpica, J.M., Garc[iacute]a-Arenal, F. Genetic exchange by
recombination or reassortment is infrequent in natural populations of a
tripartite RNA plant virus. Journal of Virology 1997; 71:934-40.
62. Sal[aacute]nki, K., Carr[eacute]re, I., Jacquemond, M.,
Bal[aacute]zs, E., Tepfer, M. Biological properties of
pseudorecombinant and recombinant strains created with cucumber mosaic
virus and tomato aspermy virus. Journal of Virology 1997; 71:3597-602.
63. Aaziz, R., Tepfer, M. Recombination between genomic RNAs of two
cucumoviruses under conditions of minimal selection pressure. Virology
1999; 263:282-9.
64. Spitsin, S., Steplewski, K., Fleysh, N., Belanger, H.,
Mikheeva, T., Shivprasad, S. et al. Expression of alfalfa mosaic virus
coat protein in tobacco mosaic virus (TMV) deficient in the production
of its native coat protein supports long-distance movement of a
chimeric TMV. Proceedings of the National Academy of Sciences 1999;
96:2549-53.
65. Allison, R.F., Janda, M., Ahlquist, P. Sequence of cowpea
chlorotic mottle virus RNAs 2 and 3 and evidence of a recombination
event during bromovirus evolution. Virology 1989; 172:321-30.
66. Gibbs, M.J., Cooper, J.I. A recombinational event in the
history of luteoviruses probably induced by base-pairing between the
genomes of two distinct viruses. Virology 1995; 206:1129-32.
67. Le Gall, O.L., Lanneau, M., Candresse, T., Dunez, J. The
nucleotide sequence of the RNA-2 of an isolate of the English serotype
of tomato black ring virus: RNA recombination in the history of
nepoviruses. Journal of General Virology 2003; 76:1279-83.
68. Masuta, C., Ueda, S., Suzuki, M., Uyeda, I. Evolution of a
quadripartite hybrid virus by interspecific exchange and recombination
between replicase components of two related tripartite RNA viruses.
Proceedings of the National Academy of Sciences 1998; 95:10487-92.
69. Moonan, F., Molina, J., Mirkov, T.E. Sugarcane yellow leaf
virus: an emerging virus that has evolved by recombination between
luteoviral and poleroviral ancestors. Virology 2000; 269:156-71.
70. Desbiez, C., Lecoq, H. The nucleotide sequence of Watermelon
mosaic virus (WMV, Potyvirus) reveals interspecific recombination
between two related potyviruses in the 5' part of the genome. Archives
of Virology 2004; 149:1619-32.
71. Chenault, K.D., Melcher, U. Phylogenetic relationships reveal
recombination among isolates of cauliflower mosaic virus. Journal of
Molecular Evolution 1994; 39:496-505.
72. Pita, J.S., Fondong, V.N., Sangare, A., Otim-Nape, G.W., Ogwal,
S., Fauquet, C.M. Recombination, pseudorecombination and synergism of
geminiviruses are determinant keys to the epidemic of severe cassava
mosaic disease in Uganda. Journal of General Virology 2001; 82:655-65.
73. Zhou, X., Liu, Y., Calvert, L., Munoz, C., Otim-Nape, G.W.,
Robinson, D.J. et al. Evidence that DNA-A of a geminivirus associated
with severe cassava mosaic disease in Uganda has arisen by
interspecific recombination. Journal of General Virology 1997; 78:2101-
11.
74. Fauquet, C.M., Sawyer, S., Idris, A.M., Brown, J.K. Sequence
analysis and classification of apparent recombinant Begomoviruses
infecting tomato in the Nile and Mediterranean Basins. Phytopathology
2005; 95:549-55.
75. Monci, F., S[acute]nchez-Campos, S., Navas-Castillo, J.,
Moriones, E. A natural recombinant between the Geminiviruses Tomato
yellow leaf curl Sardinia virus and Tomato yellow leaf curl virus
exhibits a novel pathogenic phenotype and is becoming prevalent in
Spanish populations. Virology 2002; 303:317-26.
76. Baliji, S., Black, M.C., French, R., Stenger, D.C., Sunter, G.
Spinach curly top virus: A newly described Curtovirus species from
southwest Texas with incongruent gene phylogenies. Phytopathology 2004;
94:772-8.
77. Mayo, M.A., Jolly, C.A. The 5'-terminal sequence of potato
leafroll virus RNA: evidence of recombination between virus and host
RNA. Journal of General Virology 1991; 72:2591-5.
78. Rubio, T., Borja, M., Scholthof, H.B., Jackson, A.O.
Recombination with host transgenes and effects on virus evolution: an
overview and opinion. Molecular Plant-Microbe Interactions 1999; 12:87-
92.
79. Lommel, S.A., Xiong, Z. Reconstitution of a functional red
clover necrotic mosaic virus by recombinational rescue of the cell-to-
cell movement gene expressed in a transgenic plant. Journal of Cell
Biochemistry 1991; 15A:151.
80. Greene, A.E., Allison, R.F. Recombination between viral RNA and
transgenic plant transcripts. Science 1994; 263:1423-5.
81. Borja, M., Rubio, T., Scholthof, H.B., Jackson, A.O.
Restoration of wild-type virus by double recombination of tombusvirus
mutants with a host transgene. Molecular Plant-Microbe Interactions
1999; 12:153-62.
82. Adair, T.L., Kearney, C.M. Recombination between a 3-kilobase
tobacco mosaic virus transgene and a homologous viral construct in the
restoration of viral and nonviral genes. Archives of Virology 2000;
145:1867-83.
83. Varrelmann, M., Palkovics, L., Maiss, E. Transgenic or plant
expression vector-mediated recombination of Plum pox virus. Journal of
Virology 2000; 74:7462-9.
84. Gal, S., Pisan, B., Hohn, T., Grimsley, N., Hohn, B.
Agroinfection of transgenic plants leads to viable cauliflower mosaic
virus by intermolecular recombination. Virology 1992; 187:525-33.
85. Schoelz, J.E., Wintermantel, W.M. Expansion of viral host range
through complementation and recombination in transgenic plants. Plant
Cell 1993; 5:1669-79.
86. Wintermantel, W.M., Schoelz, J.E. Isolation of recombinant
viruses between cauliflower mosaic virus and a viral gene in transgenic
plants under conditions of moderate selection pressure. Virology 1996;
223:156-64.
87. Frischmuth, T., Stanley, J. Recombination between viral DNA and
the transgenic coat protein gene of African cassava mosaic geminivirus.
Journal of General Virology 1998; 79:1265-71.
88. Falk, B.W., Passmore, B.K., Watson, M.T., Chin, L.S. The
specificity and significance of heterologous encapsidation of virus and
virus-like RNAs. In: Bills, D.D., Kung, S.D. Biotechnology and Plant
Protection: Viral pathogenesis and disease resistance. Singapore: World
Scientific, 1995:391-415.
89. Tepfer, M. Viral genes and transgenic plants: What are the
potential environmental risks? Biotechnology (N Y) 1993; 11:1125-32.
90. Rochow, W.F. Barley yellow dwarf virus: phenotypic mixing and
vector specificity. Science 1970; 167:875-8.
91. Creamer, R., Falk, B.W. Direct detection of transcapsidated
barley yellow dwarf luteoviruses in doubly
[[Page 19635]]
infected plants. Journal of General Virology 1990; 71:211-7.
92. Bourdin, D., Lecoq, H. Evidence that heteroencapsidation
between two potyviruses is involved in aphid transmission of a non-
aphid-transmissible isolate from mixed infections. Phytopathology 1991;
81:1459-64.
93. Taliansky, M.E., Robinson, D.J. Molecular biology of
umbraviruses: phantom warriors. Journal of General Virology 2003;
84:1951-60.
94. Osbourn, J.K., Sarkar, S., Wilson, T.M.A. Complementation of
coat protein-defective TMV mutants in transgenic tobacco plants
expressing TMV coat protein. Virology 1990; 179:921-5.
95. Candelier-Harvey, P., Hull, R. Cucumber mosaic virus genome is
encapsidated in alfalfa mosaic virus coat protein expressed in
transgenic tobacco plants. Transgenic Research 1993; 2:277-85.
96. Lecoq, H., Ravelonandro, M., Wipf-Scheibel, C., Monsion, M.,
Raccah, B., Dunez, J. Aphid transmission of a non-aphid-transmissible
strain of zucchini yellow mosaic potyvirus from transgenic plants
expressing the capsid protein of plum pox potyvirus. Molecular Plant-
Microbe Interactions 1993; 6:403-6.
97. Maiss, E., Koenig, R., Lesemann, D.E. Heterologous
encapsidation of viruses in transgenic plants and in mixed infections.
In: Jones, D.D. Biosafety Results of Field Tests of Genetically
Modified Plants and Microorganisms. Oakland: University of California ,
Division of Agriculture and Natural Resources, 1994:129-39.
98. Robinson, D.J. Environmental risk assessment of releases of
transgenic plants containing virus-derived inserts. Transgenic Research
1996; 5:359-62.
99. Robinson, D.J., Ryabov, E.V., Raj, S.K., Roberts, I.M.,
Taliansky, M.E. Satellite RNA is essential for encapsidation of
groundnut rosette umbravirus RNA by groundnut rosette assistor
luteovirus coat protein. Virology 1999; 254:105-14.
100. Fuchs, M., Gal-On, A., Raccah, B., Gonsalves, D. Epidemiology
of an aphid nontransmissible potyvirus in fields of nontransgenic and
coat protein transgenic squash. Transgenic Research 1999; 8:429-39.
101. Losey, J.E., Eubanks, M.D. Implications of pea aphid host-
plant specialization for the potential colonization of vegetables
following post-harvest emigration from forage crops. Environmental
Entomology 2000; 29:1283-8.
102. Vance, V.B., Berger, P.H., Carrington, J.C., Hunt, A.G., Shi,
X.M. 5' proximal potyviral sequences mediate potato virus X/potyviral
synergistic disease in transgenic tobacco. Virology 1995; 206:583-90.
103. OECD Environment Directorate. Consensus document on general
information concerning the biosafety of crop plants made virus
resistant through coat protein gene-mediated protection. http://
www.olis.oecd.org/olis/1996doc.nsf/62f30f71be4ed8a24125669e003b5f73/
ce3a104b8ada9e8ac12563e2003183bb/$FILE/11E63213.ENG. 1996.
104. Miller, W.A., Koev, G., Mohan, B.R. Are there risks associated
with transgenic resistance to luteoviruses? Plant Disease 1997; 81:700-
10.
105. Pruss, G.J., Ge, X., Shi, X.M., Carrington, J.C., Vance, V.B.
Plant viral synergism: the potyviral genome encodes a broad-range
pathogenicity enhancer that transactivates replication of heterologous
viruses. The Plant Cell 1997; 9:859-68.
106. Garc[iacute]a-Arenal, F., Malpica, J.M., Fraile, A. Evolution
of plant virus populations: The role of genetic exchange. In:
Fairbairn, C., Scoles, G., McHughen, A. Proceedings of the 6th
International Symposium on the Biosafety of Genetically Modified
Organisms. Saskatoon, Canada: University Extension Press, University of
Saskatchewan, 2000:91-6.
107. Thomas, P.E., Hassan, S., Kaniewski, W.K., Lawson, E.C.,
Zalewski, J.C. A search for evidence of virus/transgene interactions in
potatoes transformed with the potato leafroll virus replicase and coat
protein genes. Molecular Breeding 1998; 4:407-17.
108. Fuchs, M., Klas, F.E., McFerson, J.R., Gonsalves, D.
Transgenic melon and squash expressing coat protein genes of aphid-
borne viruses do not assist the spread of an aphid non-transmissible
strain of cucumber mosaic virus in the field. Transgenic Research 1998;
7:449-62.
109. Lin, H.X., Rubio, L., Smythe, A., Jiminez, M., Falk, B.W.
Genetic diversity and biological variation among California isolates of
Cucumber mosaic virus. Journal of General Virology 2003; 84:249-58.
110. Vigne, E., Komar, V., Fuchs, M. Field safety assessment of
recombination in transgenic grapevines expressing the coat protein gene
of Grapevine fanleaf virus. Transgenic Research 2004; 13:165-79.
111. Allison, R.F., Schneider, W.L., Greene, A.E. Recombination in
plants expressing viral transgenes. Seminars in Virology 1996; 7:417-
22.
112. Rovere, C.V., del Vas, M., Hopp, H.E. RNA-mediated virus
resistance. Current Opinion in Biotechnology 2002; 13:167-72.
113. Allison, R.F., Schneider, W.L., Deng, M. Risk assessment of
virus resistant transgenic plants. In: Schiemann, J. The Biosafety
Results of Field Tests of Genetically Modified Plants and
Microorganisms. Berlin: Biologische Bundesanstalt f[uuml]r Land- und
Forstwirtschaft, 2000:186-8.
114. Dinant, S., Blaise, F., Kusiak, C., Astier-Manifacier, S.,
Albouy, J. Heterologous resistance to potato virus Y in transgenic
tobacco plants expressing the coat protein gene of lettuce mosaic
potyvirus. Phytopathology 1993; 83:819-24.
115. Teycheney, P.Y., Aaziz, R., Dinant, S., Sal[aacute]nki, K.,
Tourneur, C., Bal[aacute]zs, E. et al. Synthesis of (-)-strand RNA from
the 3' untranslated region of plant viral genomes expressed in
transgenic plants upon infection with related viruses. Journal of
General Virology 2000; 81:1121-6.
116. AIBS. Transgenic virus-resistant plants and new plant viruses.
http://www.aphis.usda.gov/ppq/biotech/virus/95_virusrept.pdf. 1995.
117. Greene, A.E., Allison, R.F. Deletions in the 3' untranslated
region of cowpea chlorotic mottle virus transgene reduce recovery of
recombinant viruses in transgenic plants. Virology 1996; 225:231-4.
118. Nagy, P.D., Ogiela, C., Bujarski, J.J. Mapping sequences
active in homologous RNA recombination in brome mosaic virus:
prediction of recombination hot spots. Virology 1999; 254:92-104.
119. Miller, W.A., Koev, G., Beckett, R. Issues surrounding
transgenic resistance to the Luteoviridae. In: Schiemann, J. The
Biosafety Results of Field Tests of Genetically Modified Plants and
Microorganisms. Berlin: Biologische Bundesanstalt f[uuml]r Land- und
Forstwirtschaft, 2000:203-9.
120. Nagy, P.D., Zhang, C., Simon, A.E. Dissecting RNA
recombination in vitro: role of RNA sequences and the viral replicase.
The EMBO Journal 1998; 17:2392-403.
121. Gibbs, M. Risks in using transgenic plants? Science 1994;
264:1650-1.
122. Hull, R. Risks in using transgenic plants? Science 1994;
264:1649-50.
123. U.S. Environmental Protection Agency. Bacillus thuringiensis
Cry3Bb1 Protein and the Genetic Material Necessary for its Production
(Vector ZMIR13L) in Event MON863 Corn (006484) Biopesticide
Registration Action Document (BRAD). http://www.epa.gov/pesticides/biopesticides/ingredients/tech_docs/brad_006484.htm. 2003.
[[Page 19636]]
124. U.S. Environmental Protection Agency. Biopesticides
Registration Action Document (BRAD)--Bacillus thuringiensis Cry2Ab2
protein and its genetic material necessary for its production in
cotton. http://www.epa.gov/pesticides/biopesticides/ingredients/tech--
docs/brad--006487.pdf. 2002.
125. Gonsalves, D., Manshardt, R. Petition 96-051-01p for
Determination of Regulatory Status: Transgenic Papaya lines 55-1 and
their Derivatives. 1996.
126. Codex Alimentarius Commission. Guideline for the Conduct of
Food Safety Assessment of Foods Derived from Recombinant-DNA Plants.
2003.
127. Smalla, K., Borin, S., Heuer, H., Gebhard, F., van Elsas,
J.D., Nielsen, K. Horizontal transfer of antibiotic resistance genes
from transgenic plants to bacteria -- are there new data to fuel the
debate? In: Fairbairn, C., Scoles, G., McHughen, A. Proceedings of the
6th International Symposium on the Biosafety of Genetically Modified
Organisms. Saskatchewan: University Extension Press, 2000:146-54.
128. Tolin, S.A. Persistence, establishment, and mitigation of
phytopathogenic viruses. In: Levin, M.A., Strauss, H.S. Risk Assessment
in Genetic Engineering. New York: McGraw-Hill, Inc., 1991:114-39.
129. Abbas, M., Khan, M.M., Mughal, S.M., Khan, I.A. Prospects of
classical cross protection technique against Citrus tristeza
closterovirus in Pakistan. Horticultural Science (Prague) 2005; 32:74-
83.
130. EPPO/CABI. Quarantine Pests for Europe, 2nd ed. Wallingford,
UK: CABI International, 1997.
131. International Food Biotechnology Council. Biotechnologies and
food: Assuring the safety of foods produced by genetic modification.
Regulatory Toxicology and Pharmacology 1990; 12(3).
132. Quemada, H. Food safety evaluation of a transgenic squash.
OECD Workshop on Food: Provisional Proceedings of the Safety
Evaluation. Paris: OECD, 1994:71-9.
133. Berg, J., Tymoczko, J., Stryer, L., Clarke, N. Biochemistry,
5th ed. New York: W. H. Freeman and Company, 2002.
134. Stewart, C.N.Jr., Halfhill, M.D., Warwick, S.I. Transgene
introgression from genetically modified crops to their wild relatives.
Nature Reviews Genetics 2003; 4:806-17.
135. Bartsch, D., Brand, U., Morak, C., Pohl-Orf, M., Schuphan, I.,
Ellstrand, N. Biosafety of hybrids between transgenic virus-resistant
sugar beet and swiss chard. Ecological Applications 2001; 11:142-7.
136. Spencer, L.J., Snow, A.A. Fecundity of transgenic wild-crop
hybrids of Cucurbita pepo (Cucurbitaceae): implications for crop-to-
wild gene flow. Heredity 2001; 86:694-702.
137. Ilardi, V., Barba, M. Assessment of functional transgene flow
in tomato fields. Molecular Breeding 2001; 8:311-5.
138. Fuchs, M., Chirco, E.M., Gonsalves, D. Movement of coat
protein genes from a commercial virus-resistant transgenic squash into
a wild relative. Environmental Biosafety Research 2004; 3:5-16.
139. Bartsch, D. Ecological impact of transgenic virus-resistance
in crop, weed, and wild plant populations (due to potential alterations
of plant invasiveness). In: Tepfer, M., Bal[aacute]zs, E. Virus-
resistant Transgenic Plants: Potential Ecological Impact. Berlin:
Springer, 1997:107-13.
140. Tepfer, M. Risk assessment of virus-resistant transgenic
plants. Annual Review of Phytopathology 2002; 40:467-91.
IX. Content of Official Record
EPA has established an official record for this rulemaking. The
official record includes all information considered by EPA in
developing this proposed rule including documents specifically
referenced in this action, any public comments received during an
applicable comment period, and any other information related to this
action, including any information claimed as CBI and any information
received in any of the related dockets mentioned below. This official
record includes all information physically located in the dockets
described in the following paragraph, as well as any documents that are
referenced in the documents in the dockets. The public version of the
official record does not include any information claimed as CBI.
The complete official record for this rulemaking includes:
The docket identified by the docket control number OPP-300370 for
the document entitled ``Proposed Policy: Plant-Pesticides Subject to
the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal
Food, Drug, and Cosmetic Act'' (59 FR 60496, November 23, 1994)(FRL-
4755-2).
The docket identified by the docket control number OPP-300369 for
the document entitled ``Plant-Pesticides Subject to the Federal
Insecticide, Fungicide and Rodenticide Act; Proposed Rule'' (59 FR
60519, November 23, 1994)(FRL-4755-3).
The docket identified by the docket control number OPP-300368 for
the document entitled ``Plant-Pesticides; Proposed Exemption From the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act'' (59 FR 60535, November 23, 1994)(FRL-4758-8).
The docket identified by the docket control number OPP-300371 for
the document entitled ``Plant-Pesticides; Proposed Exemption From the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act for Nucleic Acids Produced in Plants'' (59 FR 60542, November 23,
1994)(FRL-4755-5).
The docket identified by the docket control number OPP-300367 for
the document entitled ``Plant-Pesticides; Proposed Exemption From the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act for Viral Coat Proteins Produced in Plants'' (59 FR 60545, November
23, 1994)(FRL-4755-4).
The docket identified by the docket control number OPP-300370A for
the document entitled ``Plant-Pesticide Subject to the Federal
Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug,
and Cosmetic Act; Reopening of Comment Period'' (61 FR 37891, July 22,
1996)(FRL-5387-4).
The docket identified by the docket control number OPP-300368A for
the document entitled ``Plant-Pesticides; Supplemental Notice of
Proposed Rulemaking'' (62 FR 27132, May 16, 1997)(FRL-5717-2).
The docket identified by the docket control number OPP-300371A for
the document entitled ``Plant-Pesticides; Nucleic Acids; Supplemental
Notice of Proposed Rulemaking'' (62 FR 27142, May 16, 1997)(FRL-5716-
7).
The docket identified by the docket control number OPP-300367A for
the document entitled ``Plant-Pesticides; Viral Coat Proteins;
Supplemental Notice of Proposed Rulemaking'' (62 FR 27149, May 16,
1997)(FRL-5716-6).
The docket identified by the docket control number OPP-300369A for
the document entitled ``Plant-Pesticides, Supplemental Notice of
Availability of Information'' (64 FR 19958, April 23, 1999)(FRL-6077-
6).
The docket identified by the docket control number OPP-300369B for
the document entitled ``Regulations Under the Federal Insecticide,
Fungicide, and Rodenticide Act for Plant-Incorporated Protectants
(Formerly Plant-Pesticides)'' (66 FR 37772, July 19, 2001)(FRL-6057-7).
The docket identified by the docket control number OPP-300368 for
the document entitled ``Exemption From
[[Page 19637]]
the Requirement of a Tolerance Under the Federal Food, Drug, and
Cosmetic Act for Residues Derived through Conventional Breeding From
Sexually Compatible Plants of Plant-Incorporated Protectants (Formerly
Plant-Pesticides)'' (66 FR 37830, July 19, 2001)(FRL-6057-6).
The docket identified by the docket control number OPP-300371 for
the document entitled ``Exemption From the Requirement of a Tolerance
Under the Federal Food, Drug, and Cosmetic Act for Residues of Nucleic
Acids that are Part of Plant-Incorporated Protectants (Formerly Plant-
Pesticides)'' (66 FR 37817, July 19, 2001)(FRL-6057-5).
The docket identified by the docket control number OPP-300370B for
the document entitled ``Plant-Incorporated Protectants (Formerly Plant-
Pesticides), Supplemental Proposal'' (66 FR 37855, July 19, 2001)(FRL-
6760-4).
The docket identified by the docket control number EPA-HQ-OPP-2006-
0643 for the companion document entitled ``Exemption from the
Requirement of a Tolerance under the Federal Food, Drug, and Cosmetic
Act for Residues of Plant Virus Coat Proteins that are Part of a Plant-
Incorporated Protectant (PVC-Proteins)'' (FRL-8100-5) published
elsewhere in this issue of the Federal Register.
The docket identified by the docket control number EPA-HQ-OPP-2006-
0642 for this document (FRL-8100-7).
Also included in the complete official record are:
1. Public comments submitted in response to the proposals and
supplemental documents cited in the above paragraph.
2. Reports of all meetings of the Biotechnology Science Advisory
Committee and the FIFRA Scientific Advisory Panel pertaining to the
development of this proposed rule.
3. The Economic Analysis for this proposed rule and supporting
documents.
4. Support documents and reports.
5. Records of all communications between EPA personnel and persons
outside EPA pertaining to the proposed rule. (This does not include any
inter- and intra-agency memoranda, unless specifically noted in the
indices of the dockets).
6. Published literature that is cited in this document.
X. Statutory and Executive Order Reviews
A. Executive Order 12866
Pursuant to Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993), the Office of Management and
Budget (OMB) has determined that this is a ``significant regulatory
action'' because it may raise potentially novel legal or policy issues
arising out of legal mandates, the President's priorities, or the
principles set forth in the Executive Order. Therefore, this action was
submitted to OMBfor review, and changes made during that review have
been documented in the docket.
In addition, EPA has prepared an economic analysis of the impacts
related to this proposed action. The economic analysis evaluates the
quantifiablebenefits of exempting PVCP-PIPs from FIFRA requirements (40
CFR part174) and discusses the non-quantifiable benefits of this
action. Thiseconomic analysis is contained in a document entitled
``EconomicAnalysis for Proposed Exemption Under the Federal
Insecticide,Fungicide, and Rodenticide Act for Certain Plant-
IncorporatedProtectants Derived from a Plant Viral Coat Protein Gene
(PVCP-PIPs)''(called here ``the EA''). This document is available in
thedocket and is briefly summarized in Unit V.
B. Paperwork Reduction Act
Pursuant to the Paperwork Reduction Act (PRA), 44 U.S.C. 3501et
seq., an Agency may not conduct or sponsor, and a person is notrequired
to respond to a collection of information unless it displays acurrently
valid OMB control number, or is otherwise required to submitthe
specific information by a statute. The OMB control numbers for EPA's
regulations codified in Title 40 of the CFR, after appearing in the
preamble of the final rule, are further displayed either by publication
in the Federal Register or by other appropriate means, such as on the
related collection instrument or form, if applicable. The display of
OMB control numbers in certain EPA regulations is consolidated in a
list at 40 CFR 9.1.
The information collection requirements contained in thisproposed
rule have been submitted to OMB for review and approvalunder the PRA in
accordance with the procedures at 5 CFR 1320.11.The burden and costs
related to the information collection requirementscontained in this
rule are described in an addendum to a currently approved Information
Collection Request (ICR) identified as EPA ICR No. 1693.04 (OMB number
2070-0142). As defined in the PRA, ``burden'' means the total time,
effort, or financial resources expended by persons to generate,
maintain, retain, or disclose or provide information to or for a
Federal agency. This includes the time needed to review instructions;
develop, acquire, install, and utilize technology and systems for the
purposes ofcollecting, validating, and verifying information,
processing andmaintaining information, and disclosing and providing
information;adjust the existing ways to comply with any previously
applicableinstructions and requirements; train personnel to be able to
respond toa collection of information; search data sources; complete
and reviewthe collection of information; and transmit or otherwise
disclose theinformation.
This proposed rule includes information collection requirements
ofdevelopers who wish to exempt PVCP-PIPs under the provisions of
theproposed rule. Developers self-determining their exemption status
willhave to develop and maintain records supporting their
determinationand report their determination to EPA. Developers relying
on Agencydetermination of exemption status will have to develop the
informationneeded for the Agency determination and submit it to EPA.
The Agencyhas estimated that this information collection has an
estimated burdenof 21.5 hours per response for developer-determined
exemptions and23.5 hours per response for Agency-determined exemptions.
EPAestimates that there will be one submission of each type per year
fora total annual respondent burden of 45 hours.
Direct your comments on the Agency's need for this information, the
accuracy of the provided burden estimates, and any suggested methods
for minimizing respondent burden, including the use of automated
collection techniques, to EPA using the public docket that has been
established for this proposed rule (Docket ID No. EPA-HQ-OPP-2006-
0642). In addition, send a copy of your comments about the ICR to OMB
at: Office of Information and Regulatory Affairs, Office of Management
and Budget, 725 17th St., NW., Washington, DC 20503, Attention: Desk
Office for EPA ICR No. 2070-0142. Since OMB is required to complete its
review of the ICR between 30 and 60 days after April 18, 2007, please
submit your ICR comments for OMB consideration to OMB by May 18, 2007.
The Agency will consider and address comments received on
theinformation collection requirements contained in this proposal
whenit develops the final rule.
C. Regulatory Flexibility Act
Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA),
5 USC 601 et seq., the Agency hereby certifies
[[Page 19638]]
that this rule will not have a significant adverse economic impact on a
substantial number of small entities.
For purposes of assessing the impacts of today's rule on
smallentities, small entity is defined as: (1) a small business
according tothe small business size standards established by the U.S.
Small BusinessAdministration (SBA), which in this case is a pesticides
and agriculturalchemical producer (NAICS code 325320) with fewer than
500employees; a crop producer (NAICS code 111) with less than
$750,000in revenues; a college, university, or professional school
(NAICS code611310) with annual revenues less than $6.5 million; or an
entity inresearch and development in the physical, engineering, and
lifesciences (NAICS code 54171) with fewer than 500 employees; (2)
asmall governmental jurisdiction that is a government of a city,
county,town, school district or special district with a population of
less than50,000; and (3) a small organization that is any not-for-
profit enterprisewhich is independently owned and operated and is not
dominant inits field.
In determining whether a rule has a significant economic impacton a
substantial number of small entities, the impact of concern is
anysignificant adverse economic impact on small entities, since the
primarypurpose of the regulatory flexibility analyses is to identify
and addressregulatory alternatives ``which minimize any significant
economicimpact of the proposed rule on small entities'' (5 U.S.C. 603
and 604). Thus, an agency may certify that a rule will not have a
significant economic impact on a substantial number of small entities
if the rule relieves regulatory burden or otherwise has a positive
economic effect on all of the small entities subject to the rule. This
proposed rule will generate savings by exempting PVCP-PIPs with a low
probability of risk from FIFRA requirements. Given the overall
potential savings attributed to this rule, the Agency concludes that
this proposed action will not result in adverse economic impacts,
regardless of the size of the firm currently developing and testing
PVCP-PIPs or planning to develop and test PVCP-PIPs. Today's action
relieves a regulatory burden. Nevertheless, the Agency continues to be
interestedin the potential impacts of the proposed rule on small
entities andwelcomes comments on issues related to such impacts.
D. Unfunded Mandates Reform Act
Under Title II of the Unfunded Mandates Reform Act of 1995
(UMRA),Public Law 104-4, EPA has determined that this action does not
contain a Federal mandate that may result in expenditures of $100
million or more forState, local or tribal governments, in the
aggregate, or on the privatesector in any one year. The analysis of the
cost savings associated withthis action are described in Unit V of this
preamble. The requirementsof sections 202, 203, 204 or 205 of UMRA
which relate to regulatoryrequirements that might significantly or
uniquely affect smallgovernments and to regulatory proposals that
contain a significantFederal intergovernmental mandate, respectively,
do not apply totoday's rule because the rule affects only the private
sector, i.e., personsfield testing such as universities, multinational
companies,biotechnology companies, chemical companies, seed
companies;persons selling and distributing such as multinational
companies,biotechnology companies, chemical companies, seed companies;
andpersons using PVCP-PIPs such as farmers.
E. Executive Order 13132
Pursuant to Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) EPA has determined that this proposed rule does
not have federalism implications, because it will not have substantial
direct effects on the States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government, as specified
in Executive Order 13132. The primary result of this action is to
exempt certain PVCP-PIPs from most FIFRA requirements. Thus, the
requirements of section 6 of the Executive Order do not apply to this
rule.
F. Executive Order 13175
Pursuant to Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 9,
2000), EPA has concluded that this rule does not have tribal
implications because it will not have any affect on tribal governments,
on the relationship between the Federal government and the Indian
tribes, or on the distribution of power and responsibilities between
the Federal government and Indian tribes, as specified in the Executive
Order. EPA is proposing to exempt certain PVCP-PIPs from most FIFRA
requirements. This is only expected to affect the private sector, not
tribes or tribal governments. Thus, Executive Order 13175 does not
apply to this rule.
G. Executive Order 13211
This rule is not subject to Executive Order 13211, entitled Actions
Concerning Regulations that Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May 22, 2001) because it is not
designated as an ``economically significant'' regulatory action as
defined by Executive Order 12866, nor is it likely to have any
significant adverse effect on the supply, distribution, or use of
energy.
H. Executive Order 13045
This rule is not subject to Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997), because because it is not designated as
an ``economically significant'' regulatory action as defined in
Executive Order 12866 and because the Agency does not have reason to
believe that the environmental health or safety risks addressed by this
action presentdisproportionate risks to children. The Agency has
determined that thePVCP-PIPs that would be exempted by this rule pose
only a lowprobability of risk to human health, including the health of
infants andchildren, and that there is a reasonable certainty no harm
will resultto infants and children from aggregate exposure to residues
of thesePVCP-PIPs in food. Existing information suggests there are
nodisproportionate effects on infants or children from dietary or
otherexposures. EPA's assessment and the results of its assessment
arecontained in Unit VIII of the companion document publishedelsewhere
in this issue of the Federal Register exempting from the FFDCA section
408 requirement of a tolerance, residues of the plantvirus coat protein
portion of a PVCP-PIP.
I. National Technology Transfer Advancement Act
This rule does not involve a regulatory action that would
requirethe Agency to consider voluntary consensus standards pursuant
tosection 12(d) of the National Technology Transfer and AdvancementAct
of 1995 (NTTAA), (15 U.S.C. 272 note). Section 12(d) directs EPA to use
voluntary consensus standards in its regulatory activities unless to do
so would be inconsistent with applicable law or otherwise impractical.
Voluntaryconsensus standards are technical standards (e.g., materials
specifications, test methods, sampling procedures, business practices,
etc.) that are developed or adopted by voluntary consensus
[[Page 19639]]
standards bodies. The NTTAA requires EPA to provide Congress, through
OMB, explanations when the Agency decides not to use available and
applicable voluntary consensus standards when the NTTAA directs the
Agency to do so.
J. Executive Order 12898
Pursuant to Executive Order 12898, entitled Federal Actions to
Address Environmental Justice in Minority Populations and Low-
IncomePopulations (59 FR 7629, February 16, 1994), EPA has
consideredenvironmental justice related issues with regard to the
potential impactsof this action on the environmental and health
conditions in low incomeand minority communities. The Agency is
required to considerthe potential for differential impacts on sensitive
sub-populations. EPAconsidered available information on the
sensitivities of subgroups aspertains to the exemptions. EPA concluded
that no subgroup would bedifferentially affected. See also the
companion document ``Exemptionfrom the Requirement of a Tolerance under
the Federal Food, Drug, andCosmetic Act for Residues of Plant Virus
Coat Proteins that are Partof a Plant-Incorporated Protectant (PVC-
Proteins)'' published elsewherein this issue of the Federal Register.
XI. FIFRA Review Requirements
In accordance with FIFRA section 25(d), EPA submitted a draft of
thisproposed rule to the FIFRA Scientific Advisory Panel, the Secretary
of Agriculture, and to the Committee of Agriculture of the House of
Representatives and the Committee on Agriculture, Nutrition, and
Forestry of the Senate.
List of Subjects in 40 CFR Part 174
Environmental protection, Administrative practice and procedures,
Pesticides and pests.
Dated: April 9, 2007.
Stephen L. Johnson,
Administrator.
Therefore, it is proposed that 40 CFR chapter I be amended as
follows:
PART 174--[AMENDED]
1. The authority citation for part 174 would continue to read as
follows:
Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a and 371.
2. By alphabetically adding to Sec. 174.3 new definitions to read
as follows:
Sec. 174.3 Definitions.
* * * * *
Naturally infect means to infect by transmission to a plant through
direct plant-to-plant contact (e.g., pollen or seed), an inanimate
object (e.g., farm machinery), or vector (e.g., arthropod, nematode, or
fungus). It does not include infection by transmission that occurs only
through intentional human intervention, e.g., manual infection in a
laboratory or greenhouse setting.
* * * * *
PVCP-PIP is a plant-incorporated protectant derived from one or
more genes that encode a coat protein of a virus that naturally infects
plants. This includes plant-incorporated protectants derived from one
or more plant viral coat protein genes that produce only RNA and no
virus-related protein.
PVC-protein is the plant virus coat protein portion of a PVCP-PIP.
* * * * *
United States means a State, the District of Columbia, the
Commonwealth of Puerto Rico, the Virgin Islands, Guam, the Trust
Territory of the PacificIslands, and American Samoa.
Unmodified means having or coding for an amino acid sequence that
is identical to an entire coat protein of a naturally occurring plant
virus.
* * * * *
Virtually unmodified means having or coding for an amino acid
sequence that is identical to an entire coat protein of a naturally
occurring plant virus, except for the addition of one or two amino
acids at the N- and/or C-terminus other than cysteine, asparagines,
serine, and threonine and/or the deletion of one or two amino acids at
the N- and/or C-terminus.
Weedy species means a species that is an aggressive competitor in
natural ecosystems.
* * * * *
3. In Sec. 174.21 by revising the introductory text and paragraph
(c) to read as follows:
Sec. 174.21 General qualifications for exemptions.
A plant-incorporated protectant is exempt from the requirements of
FIFRA, other than the requirements of Sec. 174.71, if it meets all of
the following criteria. Plant-incorporated protectants that are not
exempt from the requirements of FIFRA under this subpart are subject to
all the requirements of FIFRA.
* * * * *
(c) Any inert ingredient that is part of the plant-incorporated
protectant is on the list codified at Sec. Sec. 174.485 through
174.486.
4. By adding Sec. 174.27 to subpart B to read as follows:
Sec. 174.27 Plant-incorporated protectant derived from a coat protein
gene(s) from a virus(es) that naturally infects plants (PVCP-PIP).
In order for a plant-incorporated protectant derived from one or
more genes that encode a coat protein of a virus that naturally infects
plants (PVCP-PIP) to be exempt, the criteria in paragraphs (a), (b),
and (c) and the requirements in paragraph (d) of this section must all
be satisfied.
(a) The criterion in paragraph (a) of this section is satisfied if
either paragraph (a)(1) or paragraph (a)(2) of this section applies:
(1) The plant containing the PIP is one of the following: anthurium
(Anthurium spp.), asparagus (Asparagus officinale), avocado (Persea
americana), banana (Musa acuminata), barley (Hordeum vulgare), bean
(Phaseolus vulgaris), cacao (Theobroma cacao), carnation (Dianthus
caryophyllus), chickpea (Cicer arietinum), citrus (Citrus spp., e.g.,
Citrus aurantifolia, Citrus limon, Citrus paradisii, Citrus sinensis),
coffee (Coffea arabica and Coffea canephora), corn (Zea maize), cowpea
(Vigna unguiculata), cucumber (Cucumis sativus), gerbera (Gerbera
spp.), gladiolus (Gladiolus spp.), lentil (Lens culinaris), mango
(Mangifera indica), orchids (Orchidaceae), papaya (Carica papaya), pea
(Pisum sativum), peanut (Arachis hypogaea), pineapple (Ananas comosus),
potato (Solanum tuberosum), soybean (Glycine max), starfruit (Averrhoa
carambola), sugarcane (Saccharum officinarum), or tulips (Tulipa spp.).
(2) The Agency determines after review that the plant containing
the PIP meets paragraphs (a)(2)(i), (a)(2)(ii), and (a)(2)(iii) of this
section:
(i) Has no wild or weedy relatives in the United States with which
it can form viable hybrids in nature.
(ii) Is not a weedy or invasive species outside of agricultural
fields in the United States.
(iii) Is unlikely to establish weedy or invasive populations
outside of agricultural fields in the United States even if the plant
contains a PVCP-PIP.
(b) The criterion in paragraph (b) of this section is satisfied if
either paragraph (b)(1)(i), paragraph (b)(1)(ii), or paragraph (b)(2)
of this section applies:
(1)(i) The viral pathotype used to create the PVCP-PIP has
naturally infected plants in the United States and naturally infects
plants of the same species as those containing the PVCP-PIP, or
(ii) The genetic material that encodes the pesticidal substance or
leads to the production of the pesticidal substance is
[[Page 19640]]
inserted only in an inverted repeat orientation or lacking an
initiation codon for protein synthesis such that no PVC-protein is
produced in the plant.
(2) The Agency determines after review that viruses that naturally
infect the plant containing the PVCP-PIP are unlikely to acquire the
coat protein sequence through recombination and produce a viable virus
with significantly different properties than either parent virus.
(c) The criterion in paragraph (c) of this section is satisfied if
either paragraph (c)(1) or paragraph (c)(2) of this section applies:
(1) The genetic material that encodes the pesticidal substance or
leads to the production of the pesticidal substance:
(i) Is inserted only in an inverted repeat orientation or lacking
an initiation codon for protein synthesis such that no PVC-protein is
produced in the plant, or
(ii) Encodes only a single virtually unmodified viral coat protein.
Multiple PVC-proteins could each separately meet this criterion.
Chimeric PVC-proteins do not qualify.
(2) The Agency determines after review that the genetic material
that encodes the pesticidal substance or leads to the production of the
pesticidal substance:
(i) Encodes a protein that is minimally modified from a coat
protein from a virus that naturally infects plants, or
(ii) Produces no protein.
(d)(1) Records to support exemption determinations made by the
developer of a PVCP-PIP under paragraphs (a)(1), (b)(1), or (c)(1) of
this section; to support a submission of information under paragraphs
(a)(2), (b)(2), or (c)(2) of this section; or to support a
certification made by the developer that a PVCP-PIP meets Sec.
174.21(b) and/or Sec. 174.21(c) must be maintained by the developer of
the product for the duration of time that the PVCP-PIP is sold or
distributed. Such records must be made available for inspection and
copying, or otherwise submitted to the Agency for review upon request
by EPA or its duly authorized representative.
(2) Information adequate to support claims for an Agency-determined
exemption must be submitted for review to the Office of Pesticide
Programs, Attention: PVCP-PIP Exemption.
(3) A statement notifying the Agency and certifying the accuracy of
any determination made by the developer that a PVCP-PIP meets Sec.
174.21(b), Sec. 174.21(c), paragraph (a)(1) of this section, paragraph
(b)(1) of this section, and/or paragraph (c)(1) of this section must be
signed by the developer and submitted to the Office of Pesticide
Programs, Attention: PVCP-PIP Exemption. Any such statement must be
submitted at the time of a first submission, if any, of information
under paragraph (d)(2) of this section for a particular PVCP-PIP. If a
PVCP-PIP satisfies paragraphs (a)(1), (b)(1), and (c)(1)) of this
section and Sec. Sec. 174.21(b) and (c), the developer must submit a
notification to the Agency of that determination and certify that the
PVCP-PIP qualifies for exemption under FIFRA, i.e., that the PVCP-PIP
meets Sec. Sec. 174.21(a), (b), and (c).This certification must
contain:
(i) The name of the crop (including genus and species) containing
the PVCP-PIP.
(ii) The name of the virus from which the coat protein gene was
derived.
(iii) The name of the virus(es) to which resistance is conferred.
(iv) When available, a unique identifier.
5. By revising Sec. 174.480 to read as follows:
Sec. 174.480 Scope and purpose.
This subpart lists the inert ingredients that may be used in a
plant-incorporated protectant listed in subpart B of this part and
whose residues are either exempted from the requirement of a tolerance
under FFDCA or no tolerance would otherwise be required.
6. By adding Sec. 174.486 to read as follows:
Sec. 174.486 Inert ingredients that may be used with PIPs in certain
plants.
The following must be used in a plant that satisfies Sec.
174.27(a) in order to be exempt from the requirements of FIFRA.
(a) Beta-D-glucuronidase (GUS) from Escherichia coli and the
genetic material necessary for its production.
(b) Neomycin phosphotransferase II (NPTII) and the genetic material
necessary for its production.
(c) Phosphomannose isomerase (PMI) and the genetic material
necessary for its production.
(d) CP4 enolpyruvylshikimate-3-phosphate (CP4 EPSPS) and the
genetic material necessary for its production.
(e) Glyphosate oxidoreductase (GOX or GOXv247) and the genetic
material necessary for its production.
(f) Phosphinothricin acetyltransferase (PAT) and the genetic
material necessary for its production.
(g) Partial tetracycline resistance gene under the control of a
bacterial promoter as present in papaya line 55-1.
[FR Doc. E7-7297 Filed 4-17-07; 8:45 am]
BILLING CODE 6560-50-S