Document ID: EPA-HQ-OPP-2006-0642-0002
Agency: epa
Document Type: Notice
Title: 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
Posted Date: 2007-04-18T04:00Z

[Federal Register: April 18, 2007 (Volume 72, Number 74)]
[Proposed Rules]               
[Page 19589-19640]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18ap07-18]                         

[[Page 19589]]

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Part II

Environmental Protection Agency

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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

[[Page 19590]]

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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.

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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: kramer.melissa@epa.gov.

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

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    45. OECD Environment Directorate. Consensus document on the biology 
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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.
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of Solanum tuberosum subsp. tuberosum (potato). http://www.oecd.org/dataoecd/25/62/27854542.pdf.
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    49. United States Department of Agriculture Animal and Plant Health 
Inspection Service. USDA/APHIS Petition 94-257 for Determination of 
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BT6, BT10, BT12, BT16, BT17, BT18, and BT23. 1995.
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of Glycine max (L.) Merr. (soybean). http://www.olis.oecd.org/olis/2000doc.nsf/4f7adc214b91a685c12569fa005d0ee7/c125692700623b74c1256996003e87fc/$FILE/00085953.PDF.
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transgene containment. Ecology Letters 2004; 7:213-20.
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of transgenically mitigated tobacco in competition with the wild type 
in a replacement series. Planta 2005; 222:372-85.
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risks of plants used for bioremediation, including risks of transgene 
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    58. Falk, B.W., Bruening, G. Will transgenic crops generate new 
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specificity and significance of heterologous encapsidation of virus and 
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infected plants. Journal of General Virology 1990; 71:211-7.
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coat protein-defective TMV mutants in transgenic tobacco plants 
expressing TMV coat protein. Virology 1990; 179:921-5.
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Raccah, B., Dunez, J. Aphid transmission of a non-aphid-transmissible 
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Taliansky, M.E. Satellite RNA is essential for encapsidation of 
groundnut rosette umbravirus RNA by groundnut rosette assistor 
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of an aphid nontransmissible potyvirus in fields of nontransgenic and 
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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, 
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information concerning the biosafety of crop plants made virus 
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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.
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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 
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    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.
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plants expressing viral transgenes. Seminars in Virology 1996; 7:417-
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    112. Rovere, C.V., del Vas, M., Hopp, H.E. RNA-mediated virus 
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Albouy, J. Heterologous resistance to potato virus Y in transgenic 
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region of cowpea chlorotic mottle virus transgene reduce recovery of 
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    118. Nagy, P.D., Ogiela, C., Bujarski, J.J. Mapping sequences 
active in homologous RNA recombination in brome mosaic virus: 
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recombination in vitro: role of RNA sequences and the viral replicase. 
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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]

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