Document ID: EPA-HQ-OPP-2008-0742-0076
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-05-10T04:00Z

EPA Response to Public Comments on 

Biopesticides Registration Action Document

Proposed Decision

 

Coat Protein Gene of Plum Pox Virus

PC Code: 006354

May 10, 2010

U.S. Environmental Protection Agency

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division



The Biopesticides and Pollution Prevention Division (BPPD) of the Office
of Pesticide Programs, EPA, has analyzed and considered all comments
submitted on the Agency's preliminary registration decision for the C5
HoneySweet Plum, containing the new plant-incorporated protectant active
ingredient, Coat Protein Gene of the Plum Pox Virus (CPG-PPV).  These
comments were submitted to docket EPA-HQ-OPP-2008-0742.   This document
responds to significant comments received.

General Issues

Support for the registration

A number of comments were received on matters generally related to the
Agency's preliminary decision to register the C5 HoneySweet Plum. 
Fifty-one comments expressed support for the registration of this PIP
pesticide.  Representative of these comments was number 0016:  "I concur
with the panel of regulators that this product does not pose any undue
risks to the environment or human health. Quite the contrary, the
‘Honeysweet’ is a promising technology that has great potential to
mitigate a devastating invasive virus."  Similarly, number 0018 noted: 
"Viral coat protein genes have been known for over 20 years to provide
lasting—and very safe---resistance in plants against viruses (Fuchs &
Gonsalves, 2007 Annual Rev. Phytopathology 45:173-202.).  There is a
compelling need for this genetically modified tree with plum pox
resistance, since the only other known means to control the virus are
economically damaging quarantine and eradication measures.  Once a tree
is infected, it must be destroyed. Eradication of plum pox in
Pennsylvania in 1999 resulted in destruction of 1600 acres of trees at a
cost of $40 million (Scorza et al., 2007. Acta Hortic. 738:669-671). 
Eradication of plum pox in Canada has resulted in destruction of 354,798
trees at a cost of Can.$180 million (U.S.$174 million) by the end of
March 2011." [citation omitted] [emphasis in original]  Also, number 63:
 "HoneySweet plum is highly resistant to Plum pox virus (PPV), a
devastating virus of stone fruits worldwide.  Resistance to PPV in
HoneySweet is due to the expression of a plant-incorporated protectant
that activates the anti-viral pathways of RNA silencing, a natural and
potent defense mechanism of plants against viruses.  Since no host
resistance to PPV is known in European plum, HoneySweet offers a
practical and unique solution to manage PPV.  Extensive field risk
assessment studies done in various ecosystems have shown that HoneySweet
does not pose undue risks to the environment and human health. Also, the
safe use of summer squash and papaya that express similar
plant-incorporated protectants and are grown for more than a decade on
thousands of acres further supports a safe use of HoneySweet."  In
addition to the comments providing a substantive rationale for
supporting the registration of C5 HoneySweet Plum, there were a number
of comments expressing general agreement with the decision.  Comment
0013 illustrates these comments:  "I have reviewed the data for this
plum. It poses no threat to the environment nor to people. I recommend
that it be deregulated and released as a new cultivar. It should be of
great use to consumers."

EPA Response:  EPA agrees that the C5 HoneySweet Plum should be
registered pursuant to our authority under Section 3 of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA).  The C5 HoneySweet
Plum registration application is supported by adequate data and/or
rationales for waiver of data requirements (in accordance with 40 C.F.R.
section 152.45), and we have determined that use of this product
consistent with the terms of the registration will not result in
unreasonable adverse effects on the environment.

Opposition to the Registration

One comment expressed general opposition to the registration.  Comment
0036 stated "Say no to GMOs!"  (Other comments expressed opposition to
the Agency registering this pesticide under FIFRA; but, supported the
sale and distribution of the C5 HoneySweet Plum.  These comments will be
addressed separately below.)

EPA Response:  Pursuant to Section 3 of FIFRA, EPA grants registrations
permitting the sale and distribution of pesticides that we have
determined will not result in unreasonable adverse effects to the
environment when used consistent with the terms and/or conditions of the
registration.  The Agency does not have the legal authority to
categorically deny registration to any class of pesticides for which it
is demonstrated that they can be used in a manner that does not result
in unreasonable adverse effects to the environment. 

FIFRA Section 3 registration comments

A number of commenters asserted that the C5 HoneySweet Plum should not
be subject to registration under FIFRA.  Commenter 0017 noted that
HoneySweet Plum does not contain any novel product that could be
considered a toxin.  The comment further states that the fact that the
transgenic component here does not produce any toxic effect "provides
EPA ample justification to exempt" this product from registration
requirements.  Commenter 0064 stated that "the molecular components of
resistance bred into plants" should not be classified as pesticides. 
Commenter 0069 stated that "there is no scientifically justifiable
reason for EPA to even consider the [CPG-PPV] to be a plant incorporated
protectant".  In particular, because no virus coat proteins are intended
to be produced, the C5 plum does not "in any meaningful sense contain a
'substance' that should be classified as a PIP."    Commenters 0070,
0072, and 0074 made similar points.

EPA Response:    

Whether a substance is a toxin or has a toxic effect is not dispositive
as to whether it is a pesticide for purposes of FIFRA regulation.  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. section 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 micro-organism (except viruses,
bacteria, or other micro-organisms on or in living man or other living
animals ) which [EPA] declares to be a pest under section 25(c)(1) of
[FIFRA].”  7 U.S.C. section 136(t).  Thus, any substance the intent of
which is to mitigate a pest is, by definition, a pesticide under the
statute.  There is no requirement that the substance be toxic, or, as
relevant here, that it be "present" in a particular form.  Where, as
here, the CPG-PPV has the effect of initiating a host plant defense
mechanism that functions to mitigate the harmful effects of a pest, it
is appropriately determined to be, and regulated as, a pesticide.

As to whether there was sufficient evidence presented to exempt the
CPG-PPV from the requirements of  FIFRA, that question was not before
the Agency.  The Applicant submitted a registration application, not a
petition to exempt this active ingredient.  The Agency reasonably
proceeded to make a decision on the application before it, rather than
effectuate an regulatory decision other than what was requested.

It is useful to provide some explanation as to why the CPG-PPV is a PIP.
 EPA explained the definition of a PIP at 66 Fed. Reg. 37771 (July 19,
2001).  As discussed therein, when traits from any living organism that
have pesticidal properties are introduced into novel organisms, the
substances are pesticides under the FIFRA definition of pesticide,
regardless of whether the pesticidal capability evolved in the plants or
was introduced by breeding or through the techniques of modern
biotechnology.  The genetic material necessary for the production of
such a pesticidal substance also meets the FIFRA statutory definition of
a pesticide.  Such genetic material is introduced into a plant with the
intent of ultimately producing a pesticidal effect even though the
genetic material may not, itself, directly affect pests.  The pesticidal
substance, along with the genetic material necessary to produce it,
produced and used in living plants, is designated a
“plant-incorporated protectant” by EPA.  Plant-incorporated
protectants are primarily distinguished from other types of pesticides
because they are intended to be produced and used in the living plant. 

FFDCA tolerance exemption comments

A number of commenters made the point that the CPG-PPV protein should
not be regulated by EPA.  Comment 0017 stated that EPA should not assess
the safety of a "hypothetical coat protein," and that it is not “even
an inert ingredient (since it is absent).”  Comment 0061 noted that
“without a pox virus coat protein product in C5 plants, there is no
chance of an allergenic reaction from the engineered DNA construct.
Further there is also very little reason to expect any hypersensitivity
reactions from contact with C5 plants.”  Comment 0069 noted that the
C5 plum does not express any novel protein prior to initiation of the
plant’s defense mechanism and that, moreover, the C5 plum is not
intended to produce novel proteins.  Comment 0070 stated that EPA should
not “require safety assessments of the proteins per se. As noted above
humans safely ingest large amounts of coat proteins of numerous plant
viruses, and it is not the active ingredient intended to produce the PIP
effect (it is the DNA that invokes RNAi, not the protein).  Earlier work
had tried to produce resistance via coat proteins, but these have
largely been superseded by RNAi induction using the coat
protein-encoding DNA or targeting other viral sequences.”  Comment
0074 noted that “the CP coding mRNAs elicit natural plant defense
responses conferring post-transcriptional gene silencing (PTGS) to
subdue viral development. As such, CP mRNAs are merely elicitors while
innate plant compounds are the key players in the resistance reaction.
Further, translational products of the transgene are undetectable.”  

EPA Response

Essentially, these comments address a key point considered in regulation
of C5 HoneySweet Plum trees – if the protein is undetectable, why is
it regulated?  EPA decided to approach this issue with caution noting
that conditions where PTGS in plants is generally known to occur include
during times of plant stress, cold weather, and upon infection with
plant viruses that express PTGS-inhibitors.  Therefore, insertion of an
open reading frame theoretically able to produce translatable mRNAs led
to analysis of the putative protein, in other words the protein that
would be produced under unknown (though probably unlikely)
circumstances.  It is the putative coat protein from genes inserted into
the C5 HoneySweet Plum, therefore, that are exempt from a food tolerance
under FFDCA as an inert ingredient.  EPA agrees with the commenters that
much of the dietary safety assessment for the coat protein of plum pox
virus is based on the safe consumption of the current food supply, which
has been demonstrated to have significant levels of plant virus present.
 The dietary safety assessment for plum pox virus resistant C5 plum and
other PIPs dependent on the RNAi gene silencing phenomenon is also
facilitated by the reduced potential for any virus coat protein
production from this trait.  The safety issue comes from the fact that,
during production of the DNA for insertion into the plant, there may be
amino acids added to the plum pox coat protein or variations in the
amino acid sequence in the plum pox coat protein.  The dietary
assessment is based on the existing plum pox coat protein exposure.  The
Agency acknowledges that there is natural variability in the population
of viruses infecting plants and possibly variant coat proteins. 
However, the possible production and presence of a new protein related
to the use of a PIP requires an examination of the new protein for
dietary safety if it differs from that currently found in the food
supply.

Label comments

A number of comments were received asserting that the C5 HoneySweet Plum
should not be distributed with a FIFRA label and that any label that did
accompany the product should not include the statement “PPVR: not
intended for use in organic agriculture”.

EPA Response:  

As a point of clarification, we note that the proposed label included in
the docket was not intended to be a label to accompany the product in
commerce.  Consistent with our practice with other registered PIPs, the
FIFRA label for the C5 HoneySweet Plum is not required to accompany the
product distributed in commerce.  Rather, the label is approved
concomitant with the registration and is held by the registrant.  We
placed the label in the docket because this is our normal practice for
all products for which we have made a preliminary decision to register
and which are subject to public comment.  We did not intend to
inadvertently send a signal that this is a label that would be required
as a term of the registration to accompany the product in commerce.  

Consistent with practice for other registered PIPs, the C5 HoneySweet
Plum will be accompanied by labeling developed by the registrant.  This
labeling will set forth specific terms of agreement between USDA and the
distributors of the budwood.  This is consistent with the current
practice for other registered PIP products.

 

Similarly, with respect to the statement regarding whether the C5
HoneySweet Plum may be used in organic production, we are not requiring
as a term of the registration granted to USDA that the statement “not
intended for use in organic agriculture” be included on the C5
HoneySweet Plum label.

EPA Response to Public Comments on 

BRAD Proposed Decision:  Plum Pox 

May 10, 2010

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