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
EPA Response to Public Comments on 

BRAD Proposed Decision: Plum Pox 

May 10, 2010

2

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 to Public Comments on 

BRAD Proposed Decision: Plum Pox 

May 10, 2010

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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 
EPA Response to Public Comments on 

BRAD Proposed Decision: Plum Pox 

May 10, 2010

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form of terrestrial or aquatic plant or animal life or virus, bacteria, or other microorganism (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 
EPA Response to Public Comments on 

BRAD Proposed Decision: Plum Pox 

May 10, 2010

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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 
EPA Response to Public Comments on 

BRAD Proposed Decision: Plum Pox 

May 10, 2010

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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.