U.S.
ECONOMY > Technology > Biotechnology > United States Regulatory Oversight in Biotechnology Responsible Agencies - Overview
Plant-Pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act; Proposed Rule
[Federal Register: November 23, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 152 and 174
[OPP-300369; FRL-4755-3]
RIN 2070-AC02
Plant-Pesticides Subject to the Federal Insecticide, Fungicide,
and Rodenticide Act; Proposed Rule
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: The substances plants produce to protect themselves against
pests and disease are considered to be pesticides under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) definition of
``pesticide'' (i.e., if they are ``. . . intended for preventing,
destroying, repelling or mitigating any pest. . .''). These substances,
along with the genetic material necessary to produce them, are
designated ``plant-pesticides'' by EPA. EPA proposes to amend an
existing regulation and to create a new regulation to clarify the
relationship between plants and plant-pesticides and their regulatory
status under FIFRA. EPA also proposes to exempt from FIFRA requirements
classes of plant-pesticides that the Agency has determined pose low
probability of risk and are not likely to cause unreasonable adverse
affects on the environment. Recognizing the unique characteristics of
plant-pesticides, the Agency proposes to create a new part in the CFR
for regulations unique to plant-pesticides.
DATES: Comments identified by the docket control number [OPP-300369]
must be received on or before January 23, 1995.
ADDRESSES: Submit written comments by mail to: Program Resources
Section, Public Response and Program Resources Branch, Field Operations
Division (7506C), Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to Rm. 1132, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). Information so marked will
not be disclosed except in accordance with procedures set forth in 40
CFR part 2. A copy of the comment that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice. All
written comments will be available for public inspection in Rm. 1132 at
the Virginia address given above from 8 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Bernice Slutsky, Science and
Policy Staff, Office of Prevention, Pesticides and Toxic Substances
(7101), Environmental Protection Agency, 401 M St., SW., Washington, DC
20460, Telephone number: (202) 260-6900.
SUPPLEMENTARY INFORMATION:
I. Introduction
EPA proposes to clarify the regulatory status, under FIFRA, of
pesticidal substances produced in plants (plant-pesticides) and of
plants that produce pesticidal substances and act as biological control
agents. EPA defines a biological control agent as ``any living organism
applied to or introduced into the environment that is intended to
function as a pesticide against another organism declared to be a pest
by the Administrator'' (40 CFR 152.3). EPA also proposes to exempt from
FIFRA regulation certain types of pesticidal substances produced in
plants that EPA believes do not warrant regulation.
In the Federal Register of June 2, 1982 (47 FR 23928), EPA
promulgated a final regulation under FIFRA section 25(b) that exempted
all biological control agents, except for certain microorganisms, from
the requirements of FIFRA. This exemption was promulgated because EPA
found that the risks posed by biological control agents other than
microorganisms were adequately addressed by other Federal agencies such
as the U.S. Department of Agriculture's (USDA's) Animal and Plant
Health and Inspection Service (APHIS) and the U.S. Department of the
Interior. Although plants used as biological control agents were not
specifically addressed in 40 CFR 152.20 or in the June 2, 1982, Federal
Register document, EPA has considered these plants to be excluded from
regulation under FIFRA through this exemption. EPA continues to believe
that plants used as biological control agents are adequately regulated
by other Federal agencies. However, EPA believes that the status of
pesticidal substances produced in plants (i.e., plant-pesticides)
requires regulatory clarification.
Although plants used as biological control agents were exempted
from FIFRA regulation under 40 CFR 152.20, substances that are
extracted from plants and used as pesticides are not similarly
exempted. For example, chrysanthemums produce pyrethrum, a substance
that has insecticidal activity. Chrysanthemums that produce pyrethrum
are exempt from regulation when used as biological control agents
(i.e., living chrysanthemums), but pyrethrum itself, as the pesticide
substance, is not exempt when it is extracted from chrysanthemum plants
and applied to other plants as an insecticide.
This distinction is reasonable in light of the potential for
increased and unique exposures due to large-scale application of
extracted pyrethrum to plants that do not naturally produce it. The use
of extracted pyrethrum as an insecticide can involve exposure to the
pesticide over large acreages, whereas the exposure associated with
pyrethrum produced by living chrysanthemum plants would not be expected
to reach such proportions. In addition, application of pyrethrum beyond
the environment in which it is normally produced (i.e., beyond the
living chrysanthemum plant) could result in new or unique exposures of
nontarget organisms, including humans.
Although it has been EPA's policy under FIFRA to regulate
pesticidal substances that have been extracted from plants, to date the
Agency has not clearly stated its policies for regulation of pesticidal
substances that are produced in living plants and function in situ to
protect the plant from pests or disease (i.e., not extracted from the
plants). This proposed rule is designed to provide such clarification.
FIFRA section 2(u) defines ``pesticide'' as: ``(1) any substance or
mixture of substances intended for preventing, destroying, repelling,
or mitigating any pest, and (2) any substance or mixture of substances
intended for use as a plant regulator, defoliant, or desiccant. . . .''
The substances that are produced in plants to protect them against
pests and disease are considered to be pesticides under the definition
of FIFRA section 2, (i.e., if they are ``. . . .intended for
preventing, destroying, repelling, or mitigating any pest. . .'')
regardless of whether the pesticidal capabilities evolved in the plants
or were introduced by traditional breeding or through the techniques of
modern biotechnology. These substances, along with the genetic material
necessary to produce them, are designated ``plant-pesticides'' by the
Agency.
There are a number of types of substances produced in plants that
enable plants to resist pest attack and disease. These substances
include both those pesticidal substances that would be considered
normally a component of a plant and those that would be considered new
to a plant. Examples of plant-pesticides that would be considered
normally a component of a plant are phytoalexins (plant-produced
substances that act against phytopathogenic microorganisms). An example
of a plant-pesticide that would not be considered normally a component
of a plant is the insecticidal delta endotoxin that is produced in the
bacterium, Bacillus thuringiensis.
This proposal would clarify the relationship between plants and
plant-pesticides. It applies to all pesticidal substances produced in
living plants, including bryophytes such as mosses, seedless vascular
plants such as ferns, gymnosperms such as conifers, and angiosperms
such as most major crop plants. This proposal would reaffirm that
plants continue to be exempt under 40 CFR 152.20 and, under a new part
174 (in the 40 CFR) would codify which categories of plant-pesticides
would be exempt and which would be regulated by EPA under FIFRA.
Recognizing the unique characteristics of plant-pesticides, the Agency
will, in the future, include, in part 174, other regulations specific
to plant-pesticides.
As part of the effort to develop this proposal, EPA requested
advice from two scientific advisory committees at three meetings. On
December 18, 1992, a Subpanel of the FIFRA Scientific Advisory Panel
(SAP) was convened to review a draft proposed policy statement and to
answer a series of scientific questions concerned primarily with EPA's
proposed approach for plant-pesticides under FIFRA. On July 13, 1993, a
Subcommittee of the EPA Biotechnology Science Advisory Committee (BSAC)
was convened to address a series of scientific questions concerned
primarily with EPA's proposed approach for plant-pesticides under the
Federal Food, Drug, and Cosmetic Act (FFDCA). On January 21, 1994, a
joint BSAC/SAP Subpanel was convened to address a series of scientific
questions concerned with the scope of regulation under both FIFRA and
FFDCA and guidance for data needs for the evaluation of plantpesticides.
This proposed rule is one of several documents published in today's
issue of the Federal Register that address EPA's approach to regulating
plant-pesticides. The other documents are: (1) A proposed policy
statement that generally describes how EPA proposes to regulate plantpesticides
under FIFRA and the FFDCA (``Plant-pesticides Subject to the
Federal Insecticide, Fungicide, and Rodenticide Act and the Federal
Food, Drug, and Cosmetic Act; Proposed Policy''; (2) a proposed
exemption from the requirement of a tolerance for categories of plantpesticides
that do not result in significantly different dietary
exposures (``Plant-pesticides; Proposed Exemption from the Requirement
of a Tolerance Under the Federal Food, Drug, and Cosmetic Act''; (3) a
proposed exemption from the requirement of a tolerance for coat
proteins from plant viruses (``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'' and (4) a
proposed exemption from the requirement of a tolerance for nucleic
acids produced in plants as part of a plant-pesticide (``Plantpesticides;
Proposed Exemption from the Requirement of a Tolerance
Under the Federal Food, Drug, and Cosmetic Act for Nucleic Acids
Produced in Plants'').
II. Statutory Authority
This rule is being proposed under the authority of section 3 and
section 25(a) and (b) of the Federal Insecticide, Fungicide, and
Rodenticide Act (7 U.S.C. 136 et. seq.). FIFRA section 2(u) defines
``pesticide'' as: ``(1) any substance or mixture of substances intended
for preventing, destroying, repelling, or mitigating any pest, and (2)
any substance or mixture of substances intended for use as a plant
regulator, defoliant, or desiccant . . . ''
FIFRA section 3 provides that no person may distribute or sell in
the United States any pesticide that is not registered under the Act.
Before a product may be registered as a pesticide under FIFRA, it must
be shown that when used in accordance with widespread and commonly
recognized practice, it will not generally cause ``unreasonable adverse
effects on the environment.'' FIFRA section 2(bb) defines the term
``unreasonable adverse effects on the environment'' as any unreasonable
risk to humans or the environment, taking into account the economic,
social, and environmental costs and benefits of the use of any
pesticide. Thus, FIFRA involves a balancing of the risks presented by
the use of the pesticide against the benefits associated with the use
of that pesticide.
In addition, FIFRA section 3(a) provides that, to the extent
necessary to prevent unreasonable adverse effects on the environment,
the Administrator may by regulation limit the distribution, sale or use
of any pesticide that is not registered under FIFRA or subject to an
Experimental Use Permit under FIFRA section 5 or subject to an
emergency exemption under FIFRA section 18.
Under FIFRA section 25(b), EPA may exempt, by regulation, any
pesticide determined to be adequately regulated by another Federal
agency, or of a character which is unnecessary to be subject to the Act
in order to carry out the purposes of the Act.
III. 40 CFR Part 174
EPA is proposing to set forth, under FIFRA, a new part in 40 CFR
specifically for plant-pesticides regulated under FIFRA. In proposed
part 174, as well as at Sec. 152.20, EPA would clarify the regulatory
relationship between plants and plant-pesticides and, at Sec. 174.5,
EPA would define the scope of regulation for plant-pesticides under
FIFRA. Although EPA is not proposing in today's issue of the Federal
Register specific regulatory requirements for plant-pesticides in part
174 (e.g., labeling and Experimental Use Permit requirements), EPA
plans to propose such regulations in the future. In the interim period
before these additional regulatory amendments are proposed and
promulgated, EPA will use existing pesticide regulations (see 40 CFR
parts 152 to 173 and 40 CFR parts 177 to 186) for plant-pesticides
where applicable. However, these existing regulations were developed
generally for traditional, chemical pesticides. Because of the unique
characteristics of plant-pesticides, EPA recognizes that the existing
regulations may not always be appropriate for these products. The
characteristics of plant-pesticides such as both their production and
use in plants; their biological properties; and their potential ability
to spread and increase in quantity in the environment distinguishes
them from traditional, chemical pesticides. The Agency therefore
intends to apply the existing regulations to plant-pesticides in a
manner that addresses the unique issues associated with plants.
Producers are encouraged to consult with the Agency well in advance of
any proposed activities involving plant-pesticides. (Refer to the
Federal Register document entitled, ``Proposed Policy; Plant-pesticides
Subject to the Federal Insecticide, Fungicide, and Rodenticide Act and
the Federal Food, Drug, and Cosmetic Act.'')
IV. Definitions
Because of the unique nature of plant-pesticides, the Agency is
proposing certain definitions that will apply to plant-pesticides only.
These definitions are contained in the proposed regulatory text under
40 CFR 152.3, and in 40 CFR 174.3. The following unit describes the key
definitions for plant-pesticides under FIFRA and the rationales
underlying these definitions.
A. Definition of Plant-pesticide
EPA would define ``plant-pesticide'' under FIFRA as:
A pesticidal substance that is produced in a living plant and
the genetic material necessary for the production of the substance,
where the substance is intended for use in the living plant.
EPA is including the genetic material necessary to produce the
substance in the proposed definition of plant-pesticide for a number of
reasons. First, it is the genetic material that is introduced into the
plant with the intent that it will ultimately result in a pesticidal
effect. Additionally, EPA's regulation of pesticides is based on an
evaluation of the potential for unreasonable adverse effects associated
with the pesticidal substance, in this case, the pesticidal substance
produced in the plant. Regulation also includes risk management
considerations. A focus on the genetic material would permit the Agency
to address the potential for the spread of the pesticidal substance in
the environment through the spread of the genetic material necessary
for the production of the substance. Moreover, the amount of pesticidal
substance likely to be produced by the plant is also an important
consideration that the Agency may, in some circumstances, be able to
address through the inclusion of genetic material in the definition of
plant-pesticide. In addition, including the genetic material in the
definition of plant-pesticide would permit the Agency to address plantpesticides
during stages of the plant's life cycle or in plant parts
where the pesticidal substance itself is not produced or is produced in
very small amounts (e.g., in pollen or seed). In these cases it is
technically easier to verify the presence of the genetic material than
the pesticidal substance.
B. Definition of Active and Inert Ingredients
The regulation of pesticides under FIFRA entails the
identification of ``active ingredients'' and ``inert ingredients.''
Under FIFRA section 2, the term active ingredient means ``. . . an
ingredient which will prevent, destroy, repel, or mitigate any pest. .
. [or acts as a plant regulator, defoliant or desiccant].'' The term
inert ingredient means ``. . . an ingredient which is not active.'' EPA
recognizes that plant-pesticides have certain characteristics that are
different from those of more traditional chemical pesticides. EPA
believes that the overall characteristics of plant-pesticides require
specifically tailored active and inert ingredient definitions.
In light of this consideration, EPA proposes to use the following
definitions for plant-pesticides.
Active ingredient, when referring to plant-pesticides only,
means a pesticidal substance that is produced in a living plant and
the genetic material necessary for the production of the substance,
where the substance is intended for use in the living plant.
Inert ingredient, when referring to plant-pesticides only, means
any substance, such as a selectable marker, other than the active
ingredient, and the genetic material necessary for the production of
the substance, that is intentionally introduced into a living plant
along with the active ingredient, where the substance is used to
confirm or ensure the presence of the active ingredient.
Note that the plant-pesticide active ingredient is the plantpesticide
and therefore the proposed definition of active ingredient
for plant-pesticides is the same as the definition of plant-pesticide.
The plant-pesticide product includes both the active and inert
ingredients.
The definition of plant-pesticide and the active and inert
ingredient definitions would include all of the genetic material
``necessary for the production'' of the pesticidal and inert substance.
The following genetic regions are considered ``necessary for the
production'' of the plant-pesticide active and inert substances: (1)
The genetic material that encodes for the pesticidal substance or leads
to the production of the pesticidal substance, and (2) regulatory
regions such as promoters, enhancers, and terminators.
The genetic material can either directly encode for the pesticidal
substance or may encode for enzymes that lead to the production of a
pesticidal substance (e.g., phenylalanine ammonia-lyase (PAL) catalyzes
the first reaction in the synthesis of such phytoalexins as
pterocarpans in Leguminosae and furanocoumarins in Solanaceae and
Umbelliferae; Ref. 4). It might also include genetic regions encoding
for RNA that acts as the pesticidal substance or leads to the
production of the pesticidal substance (e.g., antisense mRNA). The
active and inert ingredients would also include any regulatory regions,
such as promoters, that control the expression of the genetic material
encoding for the pesticidal or inert substance or leading to the
production of the pesticidal or inert substance and are introduced into
the plant along with that gene. For example, a different regulatory
element could lead to the production of the pesticidal substance in new
plant parts or for new durations, resulting in new exposure scenarios.
The genetic material ``necessary for the production'' of the plant
pesticide active and inert substances does not include genetic regions
that are not involved in DNA expression (i.e., noncoding, nonexpressed
sequences such as linkers, adapters, homopolymers, and sequences of
restriction enzyme recognition sites). However, the Agency would
require information concerning these sequences if it determines that
such information is necessary for the evaluation of the active or inert
ingredient.
There may be genetic material encoding other functions (e.g.,
genetic material intended to alter the amount of carbohydrate in the
plant) that are introduced into the plant along with the active and
inert ingredients. These activities would be subject to the Food and
Drug Administration (FDA) authorities.
V. Proposed Exemptions for Plant-pesticides
EPA has attempted to identify those types of plant-pesticides that
have greater potential for environmental and/or human health risks and
to focus its regulatory scrutiny on these plant-pesticides. To exempt
from regulation those plant-pesticides having low potential for risk,
EPA is proposing to employ its exemption authority under FIFRA section
25(b). FIFRA section 25(b)(2) allows the Agency to exempt a pesticide
from the requirements of FIFRA if it is of a character unnecessary to
be subject to the Act in order to carry out the purposes of the Act.
Through FIFRA section 25(b)(2), EPA proposes to exempt certain
categories of plant-pesticides that EPA believes pose low probability
of risk and are not likely to cause unreasonable adverse effects even
in the absence of any regulatory oversight under FIFRA and, thus, are
of a character unnecessary to be subject to the Act. Those plant
pesticides not exempted would form the scope of EPA's regulatory
scrutiny under FIFRA.
EPA finds that the plant-pesticides it is proposing to exempt have
a low probability of risk and have potential benefits associated with
them (e.g., economic benefits to farmers and reducing the need for
chemical pesticides) that outweigh any potential risks associated with
them, and that the low probability of risk does not justify the cost of
regulation. Therefore, the Agency proposes under 40 CFR 174.5 to
exempt, from FIFRA regulation, the categories of plant-pesticides that
EPA has identified as those that are likely to pose little risk and are
not likely to cause unreasonable adverse effects on the environment
even in the absence of regulatory oversight.
While EPA's analysis of the potential risks and benefits of plant
pesticides has led the Agency to the conclusion that some categories of
plant-pesticides warrant regulation while others do not, the Agency
cannot foresee all potential adverse effects to human health or the
environment which may potentially arise for testing and use of specific
plant-pesticides. Thus, in Sec. 174.7 EPA is proposing to require
reporting of information on adverse effects from the testing and use of
plant-pesticides that EPA is proposing to exempt in Sec. 174.5.
Proposed Sec. 174.7 is meant to address unforeseeable events resulting
from use of such pesticides. EPA believes that such events are likely
to be extremely rare; however, Sec. 174.7 is a means of ensuring that
any potential risk is addressed and that the Agency's data base is as
complete as possible. Information on potential unreasonable adverse
effects would be required to be reported if such information is
obtained, from any source, by any person who sells or distributes a
plant-pesticide. Failure to comply with Sec. 174.7 would be an unlawful
act under FIFRA section 12(a)(2)(S) and could result in an enforcement
action (for penalties) under FIFRA section 14. In addition, FIFRA
section 6(a)(2) applies to plant-pesticides that would not be exempt
under this proposed rule.
As with traditional pesticides, the underlying considerations in
analyzing risks posed by plant-pesticides are the potential for
exposure to the pesticidal substance and hazards of the pesticidal
substance to humans, other nontarget organisms, and the environment.
For plant-pesticides, exposure and hazard will be determined by the
chemical and toxicological properties of the pesticidal substance and
the biological characteristics of the plant that is producing the
substance.
The properties of the plant-pesticide, including the mechanism by
which it affects the target pest, will determine the potential for
hazards to nontarget organisms, including humans. The type of organism
exposed to the plant-pesticide will be determined by the characteristic
of the plants that produce the substance and the environment where the
plants are grown; e.g., whether the production of the substance is
limited to particular plant parts, the organisms that normally
associate with the plant, and the acreage and location planted. An
important consideration not seen with traditional pesticides is the
potential for spread of the plant's genetic material. Because plants
can reproduce sexually and/or asexually, the ability to produce the
plant-pesticide could spread through the agro- or natural ecosystems,
particularly if wild relatives acquire the ability to produce the
plant-pesticide through successful hybridization.
Such hazard and exposure considerations form the bases of the three
exemptions, discussed in Units V.A., V.B., and V.C. of this preamble,
that the Agency is proposing for plant-pesticides under FIFRA.
The benefits associated with use of some categories of plantpesticides
include the economic benefit to farmers for use of plantpesticides
in circumstances where traditional pesticides may not be as
effective (e.g., for some systemic plant pests) or may be more
expensive, thus increasing crop yield and/or reducing farmers' costs.
An additional benefit is the environmental benefit associated with
potential reduced use of pesticides that may be less environmentally
benign than these plant-pesticides.
A. Exemption of Plant-pesticides Derived from Closely Related Plants
A primary consideration in evaluating plant-pesticides is the
potential for new exposures of nontarget organisms to the pesticide. If
a plant normally produces a pesticidal substance, organisms that come
in contact with the plant have likely been exposed to that substance in
the past, perhaps over long periods of time. The potential for new
exposures to occur would be very low.
In contrast, if a plant-pesticide is not normally produced by a
plant, the organisms that come in contact with the plant may never have
been exposed to the substance. For instance, certain spiders produce a
toxin that is targeted for their insect prey. Plants are not known to
produce this toxin in nature or in cultivation. If this toxin were to
enter the gene pool of specific plants, organisms that had never
previously been exposed to the toxin could now be exposed. Prior to the
introduction of the toxin into these plants, only the insect prey of
the spider would potentially be exposed to the toxin. If plants could
now express the toxin, a different or larger group of organisms could
be exposed to it, possibly resulting in adverse effects to these
organisms. For instance, insects that feed on the plant could be
exposed to the toxin. If the toxin is found in pollen, pollinators
could also be exposed.
EPA is proposing to concentrate its regulatory efforts under FIFRA
on those plant-pesticides that are new to the plant and, thus, have the
greatest potential for exposing nontarget organisms to a new pesticidal
substance. The Agency is proposing to exempt from FIFRA regulation
those plant-pesticides that are normally a component of (not new to) a
plant. In defining, for regulatory purposes, those substances it
considers to be normally a component of a plant, the Agency is
presenting three approaches to the proposed exemption for public
comment. In selecting among these three options, the Agency will
consider how well each of the options: (1) Distinguishes, on a risk
basis, those plant-pesticides that would result in new environmental
exposures from those that would not; (2) provides a standard of
sufficient regulatory clarity so that the public, industry, and the
Agency can easily identify those plant-pesticides that would be subject
to regulation; (3) does not place an undo burden on producers/
developers; and (4) creates as similar a scope of regulation as
possible for this exemption under FIFRA as EPA is proposing under
FFDCA, given the differences in mandate and structure of the two
statutes. The three options are described below followed by a
description of terms used in the options in Unit V.A.4. of this
preamble and an analysis of the options in Unit V.A.5. of this
preamble. For the reasons discussed in Unit V.A.5. of this preamble,
EPA prefers Option 1 over Options 2 or 3.
1. Option 1: Plant-pesticides derived from sexually compatible
plants. This approach is based on the concept of sexual compatibility.
The Agency believes this concept describes a measure of relatedness
between plants and views plant-pesticides moved between sexually
compatible plants as not new to the plant. The use of the standard of
sexual compatibility is embodied in the following language from the
proposed regulatory text: [Plant-pesticides are exempt from FIFRA
requirements if:]
. . .The genetic material that encodes for a pesticidal
substance or leads to the production of a pesticidal substance is
derived from plants that are sexually compatible with the recipient
plant and has never been derived from a source that is not sexually
compatible with the recipient plant;. . .
2. Option 2: Plant-pesticides derived from plants within the same
genus. A second approach that EPA is considering for defining when a
plant-pesticide is new to the plant is a standard based on taxonomy.
Under this approach, the standard would rely on the taxonomic grouping
of genus; plant-pesticides moved between plants in the same genus would
be exempt. The assumption under this approach is that the genus
grouping correlates with a relatively high degree of relatedness among
plants even though not all plants in a genus are sexually compatible.
Similarity in traits ranging from flower morphology to the presence of
particular alkaloids and flavonoids, for example, have been used to
determine whether to classify a plant species in a particular genus and
these traits likely bespeak a high degree of relatedness. The language
defining this option would be as follows: [Plant-pesticides are exempt
from FIFRA requirements if:]
The genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance is derived from
plants that are within the same genus as the recipient plant
[regardless of sexual compatibility] and has never been derived from
a source outside of that genus;
3. Option 3: Plant-pesticides derived from plants within the same
genus or from sexually compatible plants. The third approach EPA is
considering combines the above two standards of taxonomy and sexual
compatibility. The standard under this option would rely primarily on
the taxonomic grouping of genus as a measure of relatedness.
Recognizing that some plants that are sexually compatible are
classified in different genera and assuming that sexual compatibility
bespeaks a high degree of relatedness, EPA also includes a provision
extending the exemption to include sexually compatible plants from any
genera. The language defining this option would be as follows: [Plant
pesticides are exempt from FIFRA requirements if:]
The genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance:
(1) Is derived from plants that are within the same genus as the
recipient plant [regardless of sexual compatibility] or, is derived
from plants that are sexually compatible with the recipient plant;
and
(2) Has never been derived from a source outside the same genus
that is not sexually compatible with the recipient plant.
4. Terms used in the options. The phrase ``genetic material that
encodes for the pesticidal substance or leads to the production of the
pesticidal substance'' refers to genetic material that: (1) Directly
encodes for the pesticidal substance; (2) encodes for enzymes that lead
to the production of a pesticidal substance (as in the example of the
PAL gene discussed in Unit IV. of this preamble); or (3) encodes for
RNA that acts as a pesticide or leads to the production of a pesticidal
substance (e.g., antisense RNA).
For the purposes of the options for this exemption under FIFRA,
this phrase is not intended to include regulatory regions or noncoding,
nonexpressed nucleotide sequences when the genetic material encoding
for or leading to the production of the pesticidal substance would
otherwise be exempt. For this specific exemption, these regulatory
regions and noncoding, nonexpressed nucleotide sequences may be derived
from any source. For example, if a viral promoter attached to a corn
structural gene encoding a pesticidal substance is introduced into
another corn variety, the structural gene and the viral promotor
genetic construct would meet the criteria of the options for this
exemption.
Note that whereas regulatory elements are not, for the purposes of
the proposed exemptions, considered part of the genetic material ``that
encodes for a pesticidal substance or leads to the production'' of a
pesticidal substance, regulatory elements are considered part of the
genetic material ``necessary for the production'' of a pesticidal
substance under the definitions of the plant-pesticide active and inert
ingredients (see Unit IV. of this preamble).
The definition for ``sexually compatible'' means being capable of
forming a viable zygote through the fusion of two gametes and can
include the use of bridging crosses and wide cross breeding techniques
such as surgical alteration of the plant pistil, bud pollination,
mentor pollen, immunosuppressants, in vitro fertilization, pre- and
post-pollination hormone treatments, manipulation of chromosome
numbers, and embryo culture. It can also include, for the purposes of
this exemption, ovary and ovule cultures. EPA believes that the
production of viable zygotes through these techniques indicates a
sufficient level of relatedness between the parental plants involved to
be included under the rubric of ``sexually compatible.''
The phrase ``. . . has never been derived from a source that is not
sexually compatible with the recipient plant . . .'' is meant to
indicate in the proposed regulatory text that the genetic material
would not qualify for the exemption if it is introduced into a plant
from a sexually incompatible source and subsequently introduced into
other sexually compatible plants. An example of such a situation would
be if the Bacillus thuringiensis delta endotoxin is introduced into
wheat and the endotoxin producing wheat subsequently hybridized with
rye using wide cross techniques to produce triticale. The endotoxin
produced in the triticale would not be eligible for the exemption.
5. Analysis of options. EPA's goal in developing these options for
defining an exemption under FIFRA is to identify those plant-pesticides
with a higher potential for new environmental exposures to nontarget
organisms. Under Option 1, the Agency would consider plant-pesticides
produced in sexually compatible plants to be least likely to result in
these new exposures. Since traits can be passed through a plant
population by sexual recombination, it is reasonable to predict that,
in a sexually compatible population, new exposures of organisms that
associate with plants in the population to the pesticidal substance are
unlikely.
Sexually compatible plants are more apt to share traits than are
unrelated plants. It is a common expectation that similarity is
associated with the degree of relatedness. Natural hybridization and
selection have produced groups of plants which have a common gene pool.
Generations of artificial hybridization practiced to produce improved
crops for cultivation have tended to increase the extent of relatedness
among elements of a broader segment of agricultural plants.
The practice of saving seed from desirable plants has been going on
for thousands of years and controlled crosses to produce plant hybrids
have been documented since the eighteenth century. Since the
rediscovery of Mendel's work on the inheritance of traits, there is a
base of experience of 50 to 100 years of breeding for most major crops.
During that time, it has been common agricultural practice to cross
sexually compatible wild relatives with crop plants to develop crop
varieties with better pest resistance. Techniques such as genetic
mapping reveal the presence of genetic loci in cultivated plants that
previously were considered to be present only in the wild species.
Sexually compatible crop varieties are also crossed with each other to
achieve better pest resistance in their progeny. Because of these
common practices, the potential for significantly different
environmental exposures from current crop plants is likely to be low.
EPA proposes to extend the concept of sexual compatibility to
include wide crosses because wide crosses are commonly used to expand
the plant gene pool for varietal improvement, and EPA believes that a
fairly high degree of relatedness between the parental plants is
indicated when a wide cross produces a viable zygote. However, for
regulatory purposes it is somewhat difficult to define what constitutes
a wide cross since techniques may change over time. EPA is thus
proposing, for the purposes of this proposed rulemaking, a definition
of wide crosses that is based on existing techniques with a provision
to add new techniques if they meet the definition.
Options 2 and 3 both rely on taxonomy, and this standard may also
represent an acceptable degree of relatedness. Plant species within the
same genus may have become separated by geography, timing of
pollination, or other factors to form two distinct populations no
longer sexually compatible. Events such as mutation and environmental
selection can reinforce the isolation and uniqueness of the gene pools.
However, the ability to overcome these incompatibility barriers between
species in the same genera through human intervention (e.g., bridging
crosses and wide crosses) is evidence that such plants are fairly
closely related. The majority of successful wide crosses to date have
occurred between species within the same genus.
The second option is based solely on the taxonomic standard of
genus. Sexual compatibility (including the use of bridging crosses and
wide crosses) with the recipient plant would not be a criterion. The
third option relies primarily on taxonomy but also includes the
standard of sexual compatibility. Unlike Option 2, under this option,
plant-pesticides derived from a plant outside of the same genus as the
recipient plant could still be eligible for the exemption if sexual
compatibility between the source and the recipient plant is
demonstrated.
The use of a taxonomic standard may, from a regulatory perspective,
be somewhat clearer than a standard based solely on sexual
compatibility (including bridging and wide crosses). However, taxonomy
may be a more artificial standard than sexual compatibility as a
predictor of different environmental exposures of a plant-pesticide,
particularly for unmanaged or semi-managed plants. Isolation,
adaptation to unique environments, and low natural rates of gene flow
even between populations of the same species characterize many natural
populations. For these types of plants, the taxonomic standard used in
Options 2 and 3 may not be as appropriate as the sexual compatibility
standard used in Option 1 with regard to novel exposures to plantpesticides
produced in unmanaged or semi-managed plants. In addition,
classification of plants in different genera is not fixed and could
change over time and between scientific authorities.
Option 1 is more compatible than either Option 2 or 3 with EPA's
preferred approach to plant-pesticides under FFDCA. Under FFDCA, EPA
sets tolerances for pesticide residues in foods. EPA may also exempt
pesticides from the requirement of a tolerance when such tolerance is
not needed to protect the public health. EPA is proposing to exempt
from FFDCA requirements certain plant-pesticides that would not result
in significantly new dietary exposures as it is proposing to exempt
plant-pesticides that would not result in new environmental exposures
from FIFRA requirements. Under both statutes, EPA's preferred approach
uses the standard of sexual compatibility presented in Option 1 in this
document. In addition, using a taxonomic standard alone (Option 2) is
not considered a viable option under FFDCA (see Federal Register
document entitled, ``Plant-pesticides; Proposed Exemption from the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act.''
For some crop plant varieties, e.g., potatoes, vegetative
propagation is commonly used in addition to breeding. Since
vegetatively propagated plants have the same genetic makeup, EPA
intends that a plant-pesticide produced in a vegetatively propagated
plant would meet the criteria of Option 1 as long as the plantpesticide
is either produced during vegetative propagation or, during
breeding, the original genetic source of the plant-pesticide is
sexually compatible with the recipient plant, as defined in the
proposed regulatory text. A plant-pesticide produced in vegetative
plants would meet the criteria of Option 2 and 3 as long as the plant
pesticide is produced during vegetative propagation or the original
genetic source of the plant-pesticide is in the same genus as or, in
the case of Option 3, is sexually compatible with the recipient plant.
None of the options presented in this unit are intended to exempt
plant-pesticides which are significantly different in structure or
function from the plant-pesticide as it occurs in the source plant.
Such significantly modified plant-pesticides would not be eligible for
exemption under any of the options. Rearrangements or modifications of
the sequence encoding a plant-pesticide, for example, could result in
plant-pesticides with significantly different structures and/or
functions from those in the source plant and these would not be exempt.
If this type of modification were to occur, the potential for new and
different exposures in the environment could be significant.
Under all of the approaches discussed in this unit, the Agency has
evaluated whether changes in the levels of plant-pesticides that plants
normally produce would warrant regulation under FIFRA. (Ref. 1) The
Agency's analysis indicates that changes in the levels of such
plantpesticides expressed by a plant could result in increased or decreased
exposures of nontarget organisms to a plant-pesticide. However, EPA
believes, for the reasons outlined below, that the potential for
unreasonable adverse effects from these exposures is low and these
types of plant-pesticides do not warrant regulation under FIFRA.
In deciding whether and how to regulate such plant-pesticides, EPA
first considered whether an increase in the levels of these
plantpesticides is likely to exceed the ranges normally found within and
between plant varieties (both cultivated and uncultivated). EPA
believes that increases in the levels of such plant-pesticides are not
likely to result in overall significantly different exposures of
nontarget organisms to the pesticide. The level of production of such
pesticidal substances normally varies among related plants because of
differences in genetic makeup and environmental conditions. This
variation, in turn, results in natural variations in the levels of
exposure to the pesticide. Nontarget organisms that associate with the
plants, such as birds and insect pollinators, are exposed to a range of
such plant-pesticide levels in nature.
EPA also considered the extent to which any substance can be
increased in cultivated plants without unwanted effects on other,
desirable characteristics of the plant (e.g., yield or palatability of
fruit). In general, breeders balance all of these characteristics in
developing marketable plant varieties. Considerations of
characteristics such as yield could serve to mitigate against exceeding
certain ranges of pesticide levels. Agricultural crop plants, those
most likely to be grown in large acreages with concomitant large
exposures, are not likely to be in the higher portion of the expression
range because of these constraints and are not likely to produce as
broad a range of levels of plant-pesticides that plants normally
produce. EPA anticipates that the majority of agricultural crop plants
with modified levels of plant-pesticide expression will fall within
existing ranges of pesticide levels and does not anticipate that
increasing the level of a plant-pesticide that is normally a component
of a plant would lead to a signficantly different spectrum of exposure
to the plant-pesticide.
There are also difficulties in establishing what constitutes
``significantly higher levels'' for regulatory purposes. At the July
13, 1992 meeting, the BSAC Subcommittee was specifically asked and the
subcommittee extensively discussed approaches to determining what
constitutes significantly higher levels of a plant pesticide. During
discussion at the meeting, the BSAC Subcommittee indicated it would be
very difficult to establish standards for ``significantly higher
levels'' since no formal complete data base of plant constituents and
their concentration ranges exists. Because of these difficulties, the
BSAC Subcommittee final report did not suggest a scope criterion based
on ``significantly higher levels.'' For these reasons, EPA is not
proposing, under FIFRA, to regulate using a criterion based on
``significantly higher levels'' of a plant-pesticide.
Consistent with the Agency's proposed statement of policy on
plantpesticides, EPA recognizes that plant defense compounds found in
plants that are not sexually compatible, or in other organisms such as
microorganisms, can be structurally and functionally equivalent to
compounds found in the recipient plant or in a plant sexually
compatible with the recipient plant. EPA is willing to consider, in the
future, exemptions for plant-pesticides (as are proposed for viral coat
proteins) if a producer can provide evidence that the plant-pesticide
is structurally and functionally equivalent to a plant-pesticide found
in the recipient plant or in a plant sexually compatible with the
recipient plant. Specifically, the Agency is willing to consider
development of procedures and criteria for these plant-pesticides.
Please see Request for Comment unit, Unit VII., of this preamble for a
fuller discussion of how such exemptions might be granted in future
rulemakings.
B. Exemption of Plant-pesticides That Act Primarily by Affecting the
Plant
One of EPA's primary goals in regulating pesticides is to control
the potential for adverse effects of pesticides on nontarget organisms.
An important component in the evaluation of this potential is the way
in which the pesticidal substance acts on the target pest since it
would also likely affect nontarget organisms through the same
mechanism. A pesticidal substance that acts directly on the target pest
through a toxic mechanism of action might also exert a similar effect
on other organisms. For example, a substance that acts by inhibiting
DNA synthesis of the pest could inhibit DNA synthesis in other
nontarget organisms.Toxic mechanisms of action include, but are not
limited to, those that affect: (i) Membrane permeability, (ii) cell
division, (iii) gene expression, (iv) DNA replication, or (v) other
metabolic functions (Ref. 3).
Pesticidal substances can also act through mechanisms that are less
likely to be directly toxic. Although it is possible for these
substances to adversely affect nontarget organisms, the Agency believes
that, in most cases, they pose significantly lower levels of
environmental risk than plant-pesticides with a generalized toxic
mechanism of action. Plant-pesticides that are less directly toxic
generally act primarily by affecting the plant so that the pest is
inhibited from attaching to the plant, penetrating the plant's surface
or invading the plant's tissue. For example, if a plant is modified so
that it can counter specific disease-producing compounds by
inactivating them, it is less likely that organisms that interact with
the plant in other, more beneficial ways will be affected. Similarly, a
plant may be modified to produce defense structures such as layers of
cork cells in response to infection by fungi or bacteria. These
structures form a barrier to further penetration by the pests and may
block the spread of any toxins. Other, nontarget organisms that do not
stimulate this response are not likely to be adversely affected. The
Agency believes that it would be appropriate to exempt from regulation,
under FIFRA, plant-pesticides that act through mechanisms such as
these. EPA believes that by focusing its regulatory attention on
plantpesticides that act through toxic mechanisms, it will be able to focus
on those plant-pesticides presenting higher levels of risk potential.
The proposed regulatory text presents criteria to define mechanisms of
action that are not directly toxic to the target pest.
EPA proposes that producers would assess whether they meet the
criteria presented in the proposed regulatory text. Proving eligibility
would rest with the producer claiming the exemption and the producer
could meet this responsibility by producing documentation of their
determination should a question arise concerning their claim for
exemption. If the producer's assessment is incorrect and the plantpesticide
does not qualify for the exemption, anyone selling or
distributing the plant-pesticide would be subject to enforcement
actions for selling or distributing an unregistered pesticide.
Producers would be encouraged to consult with the Agency with regard to
specific cases.
EPA is also considering whether to extend this exemption to include
substances such as plant hormones because they act by ``primarily
affecting the plant'' and do not act directly on a target pest (see
Unit VII.B. of this preamble and the proposed statement of policy
published elsewhere in today's issue of the Federal Register entitled
``Proposed Policy; Plant-pesticides Subject to the Federal Insecticide,
Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic
Act'').
C. Exemption of Coat Proteins from Plant Viruses
Coat proteins are those substances that encapsulate and protect the
genetic material of certain viruses. In some cases, when the genetic
material encoding for the coat protein is introduced into a plant's
genome, the plant is able to resist subsequent infections by the same
virus or related strains (termed viral coat protein mediated resistance
or vcp-mediated resistance). The Agency is proposing to exempt the
genetic material encoding for the coat protein and the coat protein
itself when these are introduced into a plant to effectuate viral coat
protein mediated resistance.
The Agency's proposal is based on a number of considerations which,
when taken together, bring EPA to the conclusion that coat proteins
used in vcp-mediated resistance pose low probability of risk and would
not cause unreasonable adverse effects. These considerations include
the low potential for adverse affects to nontarget organisms and the
potential benefits (environmental and economic) of utilizing vcpmediated
resistance.
To promote the fullest discussion of the issue possible, however,
the Agency is also offering for discussion an alternative, more limited
exemption. The two options are described below followed by an analysis
of the options in Unit V.C.3. of this document.
1. Option 1: Exemption of all coat proteins from plant viruses.
Under EPA's preferred option, all coat proteins from plant viruses
(vcp-mediated resistance coat protein) and the genetic material
encoding for the coat protein would be exempt from FIFRA requirements
when produced in plants for viral coat protein mediated resistance.
This exemption would include the regulatory regions and noncoding,
nonexpressed sequences needed to introduce the genetic material
encoding for the viral coat protein into the plant. This exemption is
embodied in the proposed regulatory text.
2. Option 2: Exemption of coat proteins from plant viruses produced
in plants with low potential for outcrossing to wild relatives. Under
this exemption, the Agency would limit its exemption of vcp-mediated
resistance coat proteins to those viral coat protein/plant combinations
that would have the least potential to confer selective advantage on
free-living wild relatives. The regulatory language defining these
viral coat protein/plant combinations would be as follows:
The pesticidal substance is a coat protein from a plant virus
and the genetic material necessary to produce the coat protein has
been 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.
For the purposes of this option, ``introduced into the plant's
genome'' would mean movement of nucleotide sequences into the genetic
material in a plant cell's nucleus, mitochondria, chloroplasts, and any
other plastids. ``Successfully exchange genetic material'' would mean
capable of forming zygotes viable in the laboratory and/or field
through the fusion of two gametes.
Under this option, if a plant is not on the list of plants with no
wild relatives in criterion (1), a producer would be required to submit
a written request for a determination by EPA as to whether their viral
coat protein/plant combination meets criterion (1), i.e., the Agency
would have to determine that this particular plant species has no wild
relatives in the United States. If criterion (1) could not be met, the
producer would have to submit information to the Agency to show that
criterion (2) is met or submit empirical evidence that criterion (3) is
met.
3. Analysis of options. The Agency's preferred option of exempting
all vcp-mediated resistance coat proteins is based on the limited
potential for adverse effects to nontarget organisms and/or new
exposures to the coat protein and the potential environmental and
economic benefits from using vcp-mediated resistance.
Environmental benefits associated with the use of viral coat
proteins include the reduction of the use of chemical pesticides for
viruses that are spread by vectors (usually insects). Chemical
pesticides are used for those crop plants where the most effective
method of protection against viral attack is by controlling the vector.
These pesticides may not be environmentally benign. The expression of
viral coat proteins by plants for protection from viral infection would
likely reduce the amount of chemical pesticide used to control the
vectors.
In addition to environmental benefits associated with the use of
viral coat proteins, an effective method for controlling virus
infection will have economic benefits. Plant viruses create economic
losses for a vast variety of crops by reducing yields and negatively
affecting the quality of the crop. Yield losses and quality effects for
a specific crop may vary depending on the host plant and strains of the
virus present, the incidence and activity of vectors, timing of the
infection, health and nutritional state of the plant, and weather (Ref.
5).
Presently, 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) and by controlling plant virus vectors, such as insect
populations (for vector transmitted viruses). Insecticides,
nematicides, and fungicides are all used for vector control with
varying success, depending upon the virus/vector relationship and
vector efficiency. Plants developed through conventional breeding
techniques offer some degree of virus resistance. Such resistance may
not be uniform or the virus may develop new strains. However, breeding
for resistance has not been successful for the majority of field crops
and, in particular, vegetable crops that are severely affected by
viruses (Ref. 6).
In enabling plants to resist viral attack, viral coat proteins act
in a very specific fashion, apparently adversely affecting only viruses
by blocking or limiting their ability to infect, replicate, and/or
translocate within the plant. This specificity minimizes the potential
for viral coat proteins produced in plants to adversely affect nonviral
organisms. In addition, plants in nature and in the agro-ecosystem
frequently exhibit viral infections; nontarget organisms, including
humans, have been and continue to be exposed to the viral coat proteins
with no observed adverse effects.
The possibility that environmental risk might be associated with
the use of vcp-mediated resistance was discussed at the December 18,
1992 FIFRA Scientific Advisory Panel (SAP) Subpanel meeting (see Unit
VI. of this preamble for a more thorough discussion of the issues
discussed by EPA's science advisory committees). EPA agrees with the
conclusions of the SAP Subpanel and in developing its proposal has
utilized the advice of the Subpanel to supplement EPA's own evaluation
of the scientific literature (Ref. 2). The considerations discussed by
the Subpanel included: (1) The potential for new viruses to be formed
through transcapsidation (also called heterologous encapsidation) and
recombination, (2) the potential for synergistic infections, (3) the
potential for seed transmission, and (4) the potential for the
development of selective advantage in wild relatives through successful
hybridization with the plant producing the viral coat protein. The SAP
Subpanel report offered advice on these potential risk considerations
and this advice is incorporated into the discussion below.
Most plant viruses are composed of genetic material enclosed in a
protein coat. For these viruses, the coat protein is the site of
interaction with the host plant at several stages of the viral cycle
(e.g., virus replication and movement within the plant). The coat
protein also plays an essential role in transmission by vectors such as
insects.
The issue of transcapsidation revolves around the question: if a
plant that produces a vcp-mediated resistance viral coat protein from
Virus A is infected by Virus B, can the Virus B genome be encapsidated
by the Virus A derived vcp-mediated resistance coat protein synthesized
by the plant? The consequence of such transcapsidation is the possible
extension of the host range of the virus through the possible
transmission of the Virus B genetic material by vectors that would not
normally transmit Virus B and possible infection of plants that would
not normally be exposed to and/or infected by virus B.
Heterologous encapsidation or transencapsidation has been observed
both in vitro and in vivo between coinfecting whole viruses. However,
transencapsidation between coinfecting viruses occurs more frequently
between related viruses than unrelated viruses. Although some
researchers have examined this question, there is no evidence that
transencapsidation involving vcp-mediated resistance coat proteins
produced in plants would occur at a higher frequency than has been
observed with coinfecting whole viruses.
With regard to transencapsidation involving vcp-mediated resistance
coat proteins and horizontal transmission, the SAP Subpanel concluded
that transencapsidation and transmission to other plants would most
likely occur at low levels or would not occur, depending on: (1) The
level of vcp-mediated resistance coat protein being produced by the
plant (larger concentrations of vcp-mediated resistance coat protein
would increase the probability of transcapsidation); (2) the efficiency
of transencapsidation (this varies for transencapsidation of whole
viruses); and (3) the efficiency of virus acquisition by the virus
vector. For viruses in which a specific protein-RNA-helper factor
complex is essential for transencapsidation or transmission to occur,
transmission is virtually impossible.
With regard to the potential for recombination between the plantencoded
coat protein and coat protein from an infecting virus different
from the virus contributing the coat protein gene, the consequence of
such recombination is the potential for the formation of a new virus.
The December 18, 1992, SAP Subpanel concluded that recombination is not
a risk consideration meriting regulatory oversight. Most recombination
events demonstrated to date involve either a debilitated virus under
strong selection pressure for restoration of the wildtype virus, or the
exchange of terminal regulatory sequences. In both conditions,
recombination was only demonstrated between very similar or identical
viruses. New viruses are thus unlikely to arise through a
recombinational event involving substitution of the vcp-mediated
resistance coat protein genetic material for the coat protein genetic
material of the infecting virus. Should variants of a virus arise
through recombination, these variants would be subject to selection/
competitive pressures throughout the infection cycle as are variants
that arise from recombination between replicating viruses. In addition,
there is no evidence that recombination between plant-produced coat
proteins and an infecting virus would occur at greater frequencies than
currently occur in nature between replicating viruses.
Synergistic-infection occurs when two viruses infect the same
plant, causing more severe damage than would occur if either virus
alone infected the plant. With regard to the potential for synergisticinfection,
the SAP Subpanel stated that plants expressing Virus A vcpmediated
resistance coat proteins do not express a synergistic response
when the plant is inoculated with Virus B that potentially could act
synergistically with Virus A, either because coat proteins are not
involved in synergy, or because the level of expression of the protein
is too low to potentiate the interaction.
In some species of plants, infecting viruses can be transmitted
vertically to progeny plants through seed. The question posed with vcpmediated
coat proteins is whether their presence in the plant might
affect seed transmission of infecting viruses. With regard to the
possibility of coat protein modifications affecting the ability of seed
to transmit viruses, the SAP Subpanel report states that in two cases
where the viral genetics of seed transmission of viruses has been
analyzed, genes other than those encoding the coat protein genes are
involved in potentiating the transmission. There is no reason a priori
to believe that introduction into the plant of viral coat protein genes
would affect the level of vertical transmission of viruses through
seed.
The possibility that transfer of the vcp-mediated resistance coat
protein gene to a wild relative of the modified crop plant might bestow
a selective advantage on the wild relative has also been examined by
the SAP Subpanel and the Agency. The SAP Subpanel report indicates that
even if the low probability events of transfer and expression of the
coat protein gene from crop plant to wild relative occur, the wild
plant may not acquire a selective advantage. The Subpanel report noted,
however, that while the series of events that must occur for the wild
plant to acquire a selective advantage is rather improbable, such a
series of events is not impossible.
To address this possibility, the Agency is offering an alternative
option that is a more limited exemption of vcp-mediated resistance coat
proteins. For this alternative option, the Agency has defined a set of
criteria and a process that would be used to identify those viral coat
protein/plant combinations that have the greatest potential to outcross
to wild, free-living relatives and thus have the possibility to endow
these wild relatives with a competitive advantage. Viral coat proteins
that potentially could be outcrossed would be subject to regulation.
Those viral coat protein/plant combinations with a lesser or no
probability of outcrossing and thus having a lesser or no probability
of resulting in selective advantage would be exempt from regulation. An
example of the latter situation would occur when a plant has no wild
relatives in the United States or, if it has such relatives, cannot
exchange genetic material with any of them. Under such circumstances,
there is no opportunity for selective advantage through acquisition of
the gene encoding the viral coat protein to occur in the wild relative
since successful genetic exchange would not occur.
It should be noted that neither of the exemptions described by
Option 1 nor Option 2 for viral coat proteins extends to other methods
used to create viral resistance in plants, such as the introduction of
the gene encoding for RNA replicase or the introduction of genes
encoding for satellite RNA (supernumary RNA with essentially no
sequence similarity with the host virus) into plants. EPA does not
believe it should exempt satellite RNA since single nucleotide base
changes have been shown to significantly alter the characteristics of
satellite RNAs including turning a nonnecrogenic satellite into a
necrogenic satellite. At this point, the Agency is only proposing an
exemption for vcp-mediated resistance coat proteins from plant viruses.
EPA prefers Option 1 for a number of reasons. EPA believes that the
use of vcp-mediated resistance represents little potential for
adversely affecting nontarget organisms and has a low potential for
other environmental risks even in the absence of any regulatory
oversight under FIFRA. In addition, vcp-mediated resistance is
associated with potential environmental benefits such as decreased use
of chemical pesticides and economic benefits to farmers and society
because it represents a means of controlling losses to viral disease in
the absence of effective alternative methods to control viral
infection. Option 1 represents a clearer regulatory line than Option 2
in terms of which plant-pesticides will be regulated under FIFRA.
Option 1 is more consistent with the approach taken for plantpesticides
under FFDCA. Option 1 allows the Agency to focus on plantpesticides
posing higher potential risks. In addition, under the Plant
Pest Act, USDA/APHIS addresses the potential for selective advantage
among wild plants in its review of plants genetically engineered to
produce viral coat proteins.
At the January 21, 1994 joint SAP/Biotechnology Science Advisory
Committee (BSAC) meeting (see Unit VI of this preamble), the
alternative option (Option 2) for the exemption of viral coat proteins
was discussed. The joint Subpanel agreed that Option 2 created a
process to address the possibility of selective advantage being
acquired by a wild relative through outcrossing of the vcp-mediated
resistance coat protein gene from the modified crop plant. However, the
joint Subpanel did not believe that there was a high enough level of
concern to warrant the inclusion of this option.
The report of the January 21, 1994 meeting summarizes that: (1)
Wild relatives are not found growing near many of the important crop
plants grown in the United States; (2) criteria 2 and 3 of the
alternative option address extremely rare situations, the existence of
which would be very difficult to completely disprove; (3) the potential
for increasing the ability of wild relatives to resist viral infection
is likely to be beneficial because it could lead to a reduction of the
reservoir for plant viruses; and (4) the use of vcp-mediated resistance
is more ``environmentally friendly'' than the application of chemical
pesticides to control virus vectors.
The Agency's preferred option would be to completely exempt vcpmediated
coat proteins from FIFRA regulation. Because of the potential
benefits and the low probability of risks from the use of vcp-mediated
resistance coat proteins in plants, EPA believes they warrant exemption
under FIFRA 25(b) as being ``of a character that is not necessary to be
subject to the Act.'' In addition, USDA/APHIS's review of field testing
of plants genetically engineered to produce vcp-mediated resistance
proteins addresses the possibility that the use of vcp-mediated coat
proteins may create some potential for a selective advantage to be
acquired by wild plants as well as the possibility of creating new
viruses through recombination and/or transencapsidation.
EPA is aware that, in addition to viral coat proteins, there are
viral components such as viral movement proteins and viral replicase
that are being tested for virus resistance strategies in plants. Many
of the risk issues considered by EPA for viral coat proteins may be
similar to those most likely to be addressed when examining the risks
that could potentially be associated with the use of other viral
components. USDA/APHIS's review of plants genetically engineered to
produce viral coat proteins addresses such potential risks. EPA is
committed to minimizing duplicative review of products between Federal
agencies and is also committed to developing an appropriate regulatory
approach for biologically-based pesticides in general, potentially
including pesticides based on viral components produced in plants. EPA
would tailor its regulatory procedures according to the biological
characteristics of these products. These procedures could, for example,
include expedited procedures for registration, the development of
performance-based criteria for exemptions, and specific product
exemptions. For example, the exemption of plant-pesticides that
``primarily affect the plant'' could be extended in the future, through
the inclusion of an additional criterion, to include viral components
that are used in viral resistance strategies in plants when they affect
the plant so that the viral pest cannot invade the plant.
VI. External Review
In developing its approach to regulating plant-pesticides, EPA has
requested the advice of two scientific advisory committees at three
meetings. On December 19, 1992, pursuant to section 25 of FIFRA, a
Subpanel of the FIFRA SAP was convened to review a draft policy
statement on plant-pesticides and respond to a series of scientific
questions posed by the Agency primarily on EPA's approach under FIFRA.
On July 13, 1993, a Subcommittee of the EPA BSAC was convened to
address a series of scientific questions primarily on EPA's approach
under FFDCA. On January 21, 1994, a joint meeting of a SAP/BSAC
Subpanel on plant-pesticides was held. The issues raised at these
meetings are discussed below, together with the Agency's response.
(Full reports from these meetings are available in the public docket.)
A. Substances New to the Plant
Questions on how best to describe ``substances that are new to the
plant'' were posed at all three science advisory meetings. At its
December 1992 meeting, the FIFRA SAP Subpanel was asked whether the
taxonomic demarcation of ``genus'' was appropriate, or whether some
other demarcation would be more appropriate. The Subpanel expressed
concern over an exemption based on a taxonomic definition and suggested
the Agency evaluate a series of considerations involving the potential
for quantitative and qualitative differences in exposure to a plantpesticide.
The SAP Subpanel suggested that the Agency would ``need to create a
workable balance between effective regulatory oversight and
encouragement of the development of plant-produced pesticides.''
At its July 13, 1993 meeting, the BSAC Subcommittee addressed a
related issue with regard to the regulation of plant-pesticides under
the FFDCA and human dietary exposures to plant pesticides.
Included in questions to the Subcommittee were queries on the
availability of information on current levels of exposure in the diet
to plant-pesticides in raw agricultural commodities and on which plantpesticides
might be of concern should their levels be significantly
increased.
The BSAC Subcommittee in their report stated that no formal,
complete data base for such information exists. Rather most of this
knowledge is part of breeders' experience, with breeders depending
primarily on familiarity with food crops (e.g., knowledge of which crop
plants have the ability to produce which toxicants) to ensure consumers
are not exposed to deleterious levels of such substances. In general,
little information exists on the range of levels of plant-pesticides in
plants, including ranges within the most studied grouping, food plants.
The mechanisms through which plants display resistance to pests,
moreover, have not been well worked out. Based on experience, however,
the BSAC Subcommittee suggested EPA consider a scheme based on sexual
compatibility to identify those groupings wherein plant-pesticides
might present new and novel dietary exposures and those that would not.
The use of sexual compatibility and/or taxonomy as a standard for
the potential for significantly different environmental exposures was
discussed at the January 21, 1994, joint SAP/BSAC Subpanel meeting. The
panel members were supplied with the reports of the previous meetings
and drafts of proposals analyzing the strengths and weaknesses of
approaches based on sexual compatibility and/or taxonomy. In response
to the question of whether plants in a sexually compatible population
are likely to share substances or traits, the joint Subpanel agreed
that sexually compatible plants are more likely to have a common
constitution than unrelated plants and thus movement of genetic
material between sexually compatible plants is less likely to lead to
novel exposures. Natural hybridization and selection have produced
groups of plants which have a common gene pool. Generations of
artificial hybridization to produce improved cultivated plants have
tended to increase the extent of relatedness among elements of a
broader segment of the natural diversity. In addition, modern
techniques of genetic mapping have revealed the presence of genetic
loci in cultivated plants that previously were considered to be present
only in the wild species.
In regard to the correlation of the concept of ``genus'' with
significantly different environmental exposures, the panel noted that
the taxonomic classification of a genus and the measure of sexual
compatibility are closely interrelated. Sexual compatibility tends to
promote genetic interchange and this interchange leads to populations
of plants more like each other than like groups that have been sexually
isolated. Because plants in the same genus likely have common ancestors
that at some period in their evolution were sexually compatible, plants
in the same genus are more apt to be sexually compatible with each
other than with plants from other genera. Some barriers to sexual
compatibility exist between species in the same genus even though the
species are similar taxonomically. However, many of these sexual
barriers can be overcome through the use of wide cross techniques by
breeders.
The report of the January 21, 1994, joint SAP/BSAC Subpanel
meeting, indicates that the joint Subpanel agrees that basing an
exemption on both the concept of sexual compatibility and the concept
of taxonomy should restrict the occurrence of significantly different
exposures and finds that Option 3 is a reasonable approach for
agricultural plants. However, the joint Subpanel questioned whether an
assumption of low probability of novel exposures can be extended to
wild or semi-wild plants. For these types of plants, the genus standard
``in particular,'' may result in the exemption from regulation of
plant-pesticides that may present novel exposures.
The Agency also included a question, at the January 21, 1994, joint
BSAC/SAP meeting, concerning an approach using a criterion based on the
process used to modify the plant, e.g., recombinant DNA methodologies.
As described in the report of the joint BSAC/SAP Subpanel meeting, if
the Agency were to use this approach, it would first exempt plantpesticides
developed through techniques other than those of modern
biotechnology from its regulatory scope. For those plant-pesticides
that are not exempted because they were developed through techniques of
modern biotechnology, the exemptions proposed by the Agency would apply
(i.e., the exemption based on plants' relatedness and the exemption of
plant-pesticides that act by ``primarily affecting the plant''; see
Units V.A. and V.B. of this preamble).
The joint Subpanel supported the inclusion of an option using a
criterion based on methodologies such as rDNA as a rational approach to
making the first cut as to which plant-pesticides would be regulated.
However, the joint Subpanel cautioned that further exemptions such as
those proposed by EPA should be used in conjunction with the criterion
based on methodology. In addition, the joint Subpanel recommended that
the Agency define methodologies in a way that clearly delineates to the
scientific community and the public what is and is not included in the
regulatory scope, based on current state-of-the science.
EPA Response: The Agency has chosen to propose to use under both
statutes, an approach based on sexual compatibility. First, this
approach would exempt under both FIFRA and FFDCA, plant-pesticides
having a high probability of being derived from plants having high
numbers of genes in common. Under such circumstances, the likelihood of
new or novel exposures both to the environment and in terms of human
consumption is low.
Second, use of the standard of sexual compatibility is the
preferred option under both FIFRA and FFDCA and would allow EPA to use
its authorities under FIFRA and FFDCA in concert to regulate plantpesticides,
and thus to utilize, to the extent possible in light of the
different statutory standards, similar approaches to oversight under
each of the two statutes.
Third, the Agency believes that its proposed approach would be
consistent with the December 1992 SAP Supbanel's concern that EPA ``. .
. create a workable balance between effective regulatory oversight and
encouragement of the development of plant-produced pesticides.'' Under
the preferred approach, novel exposures are not likely to occur with
plant-pesticides exchanged between plants that are sexually compatible
(See also Unit V. of this preamble for additional discussion).
With regard to the advice of the January 21, 1994, joint SAP/BSAC
Subpanel concerning the use of a process-based criterion in the scope,
if the Agency were to use this approach, plant-pesticides developed
through techniques other than those involving in vitro manipulation of
genetic material would be exempt. In order to meet the recommendations
of the joint Subpanel, the Agency would define this category of plantpesticides
in the following way: The genetic material that encodes for
the pesticidal substance or leads to the production of the pesticidal
substance is extracted from an organism and introduced into the genome
of the recipient plant or is synthesized in vitro and introduced into
the genome of the recipient plant. The exemptions proposed by the
Agency in Unit V. of this preamble would be used in concert with this
criterion. The Agency believes this approach would meet the
recommendations of the SAP/BSAC joint Subpanel. The Agency is
soliciting comment on this approach (see Unit VII.A. of this preamble).
B. Plant-pesticides That Act Primarily by Affecting the Plant
The SAP Subpanel at its December 1992 meeting considered whether
EPA's language clearly and sufficiently identified plant resistance
mechanisms that do not involve substances whose mode of action produces
a direct toxic effect on the pest. The SAP Subpanel stated that for the
most part the language EPA was proposing was clear and appropriately
identified plant resistance mechanisms whose mode of action was not
directly toxic. The Subpanel noted, however, that the issue of
resistance to toxins produced by the pests was not addressed by that
language. The Subpanel recommended insertion of the following statement
into EPA's proposed language: ``Acts in the host plant to produce
target(s) of the toxin that are resistant to the toxin's deleterious
action.''
EPA Response: EPA accepted this recommendation and modified the
language of its approach to incorporate the issue of resistance to
toxins.
C. Viral Coat Proteins
The December 18, 1992, SAP Subpanel meeting and the January 21,
1994, joint SAP/BSAC Subpanel meeting addressed the use of viral coat
protein genes to modify plants to protect the plant from damage from
viral infection. In the discussion at the December 18, 1992, SAP
Subpanel meeting, several risk considerations were identified and the
probability of occurrence of each addressed in the SAP Subpanel report.
The SAP Subpanel report stated that the probability of occurrence of
the risks examined is very low. The January 21, 1994, joint SAP/BSAC
Subpanel meeting discussed the alternative option for the exemption of
viral coat proteins from FIFRA regulation. The joint Subpanel did not
believe that the potential risks associated with the use of vcpmediated
resistance coat proteins warranted inclusion of the
alternative option. Unit IV.C.3. of this document describes how the SAP
and joint SAP/BSAC discussion of vcp-mediated resistance viral coat
proteins supplements and influences EPA's analysis.
EPA Response: EPA agrees that the probability of risks from the
introduction of viral coat protein genes into plant genomes is low, and
as its preferred option proposes to exempt these plant-pesticides from
FIFRA oversight. Because of public comments received at the December
18, 1992, SAP Subpanel meeting and the January 21, 1994, joint SAP/BSAC
meeting, however, concerning viral coat protein and selective advantage
to wild relatives of managed plants, EPA is offering for comment in
this proposal the alternative approach to viral coat proteins to allow
the fullest discussion possible.
D. U.S. Congress and U.S. Department of Agriculture
In accordance with FIFRA section 25, a draft of this proposed
regulation and a draft of the statement of policy published elsewhere
in today's issue of the Federal Register entitled ``Proposed Policy;
Plant-pesticides Subject to the Federal Insecticide, Fungicide, and
Rodenticide Act and the Federal Food, Drug, and Cosmetic Act''
(proposed policy statement) was submitted in June 1994, to the U.S.
Congress and USDA. USDA provided written comments on these two drafts
on August 18, 1994. These comments are discussed below together with
EPA's response.
1. USDA suggests that the exemption EPA is proposing under FIFRA
for viral coat proteins should be extended to include all plant viral
proteins used in viral resistance strategies and the viral genetic
sequences that encode them (including antisense constructs).
EPA response: While EPA does not believe that, at this time, it can
exempt all viral components from regulation under FIFRA it has
requested comment on such an exemption. EPA is committed to minimizing
duplicative review and would develop a coordinated approach with USDA
for viral-based products other than viral coat proteins. As the
experience base grows for these products, the two agencies can develop
a regulatory course that is mutually acceptable. These procedures
could, for example, include expedited procedures for registration, the
development of performance-based criteria for exemptions, and specific
product exemptions.
2. USDA suggested that ambiguity exists in the use of the term
``user'' in the discussion on informational labeling for plantpesticides
in the proposed policy statement.
EPA Response: EPA agrees that this discussion in the proposed
policy statement may be ambiguous and proposes to replace the term
``user'' with the term ``farmer and grower.''
3. USDA noted that EPA's exemption based on the premise that plantpesticides
derived from sexually compatible plants would not result in
new environmental exposures does not take into account that similar or
equivalent genes can be found in plants that are not sexually
compatible.
EPA's Response: EPA recognizes that plant defense compounds found
in plants that are not sexually compatible, or in other organisms such
as microorganisms, can be structurally and functionally equivalent to
compounds found in the recipient plant or in a plant sexually
compatible with the recipient plant. The Agency is willing to consider
development of procedures and criteria for these plant-pesticides. A
discussion of these procedures and criteria can be found in the Request
for Comment unit, Unit VII., of this preamble.
4. Although not included in USDA's written comments, USDA
suggested, in a discussion at an August 18, 1994 meeting between USDA
and EPA representatives, some clarifications in the discussion on plant
regulators and plant hormones in the proposed policy statement. USDA
indicated that there was some ambiguity as to how EPA would regulate
plant hormones under FIFRA.
EPA Response: EPA agrees that the plant regulator discussion may
lead to some confusion as to how EPA would regulate plant hormones. EPA
has agreed to include a discussion in the section on plant regulators
in the proposed policy statement that would more fully describe the
status of these plant-pesticides in relation to the proposed exemption
of plant-pesticides derived from sexually compatible plants or under
the proposed exemption of plant-pesticides that ``. . .primarily affect
the plant. . .'' (see Unit IV.D.in the proposal published elsewhere in
today's issue of the Federal Register entitled ``Plant-pesticides
Subject to the Federal Insecticide, Fungicide, and Rodenticide Act;
Proposed Rule'').
VII. Request for Comment
The Agency requests comments on the proposed exemptions of
plantpesticides under FIFRA.
A. Exemption of Plant-pesticides Derived from Closely Related Plants
1. Three options. EPA requests comment on whether the Agency has
appropriately identified in this proposed exemption (see Unit V.A. of
this preamble) those plant-pesticides that are not likely to result in
significantly different environmental exposures. EPA requests comment
on its three options, specifically as to whether the options
appropriately identify plant-pesticides that would not result in
significantly different exposures to nontarget organisms and whether
the language the Agency uses in the options clearly circumscribes the
appropriate groupings. EPA requests comments on which option is most
appropriate and why.
2. Criterion based on process. With regard to an exemption
criterion based on the process used to modify the plant, the Agency is
soliciting comment on the joint BSAC/SAP Subpanel advice and the
utility of an approach based on that advice (see Unit VI. of this
preamble). EPA also requests comment on whether the group of plantpesticides
that would be regulated under this approach would be
equivalent to the group of plant-pesticides that would be regulated
under Options 1, 2, or 3.
3. Equivalent plant-pesticides. As described in Unit V.A.6. of this
preamble, EPA is considering the development of procedures and criteria
for how EPA can exempt a plant-pesticide if a producer can provide
evidence that the plant-pesticide is structurally and functionally
equivalent to a plant-pesticide found in a recipient plant or in a
plant sexually compatible with the recipient plant. To effect such
rulemaking, the Agency would need to meet statutory standards under
FIFRA. In the instance of plant-pesticides, EPA would need, for
example, to determine whether a plant-pesticide is indeed structurally
and functionally equivalent to a plant-pesticide that has been
exempted.
Under such a rulemaking effort, a producer would provide
information to the Agency showing that a plant-pesticide meets the
standard for exemption under FIFRA. The Agency would respond, within a
limited period of time, to the producer as to whether the plantpesticide
meets that standard. The Agency envisions that producers
would have a fairly high degree of latitude in types of specific data
that could be used to demonstrate that a plant-pesticide meets the
standard for exemption.
The Agency is requesting comment on this framework for the
exemption rulemakings. In particular, the Agency is soliciting comment
and information on whether to incorporate specific data requirements/
methodologies into exemption criteria and on appropriate time-frames
for the Agency determinations.
The main challenge for EPA in engaging in such future rulemakings
will be to develop criteria that can be used to create a standard for
what constitutes equivalency. There are a number of different
approaches that EPA believes it could utilize. The following discussion
describes these approaches and some of the strengths and weaknesses of
these options. The Agency requests comment on these approaches and
solicits suggestions on additional factors that the Agency should weigh
in the development of criteria for equivalency.
In developing criteria for exempting a plant-pesticide from FIFRA,
the first consideration for EPA is what parameters, in general, are
good measurements for equivalency of function. The next consideration
for the Agency in the development of criteria for creating exemptions
is to examine these parameters in light of what is known concerning the
characteristics of plant defense mechanisms.
Turning first to the general parameters, some examples of the types
of parameters that the Agency could use in developing criteria for
proteinaceous substances are amino acid sequence homology,
posttranslational processing, structure, stability, receptor/ligand
specificity, and substrate specificity. For nonproteinaceous
substances, equivalence in chemical composition and structure are
additional examples of parameters that could be used as the basis for
developing criteria.
Any measures of equivalence that the Agency chooses to adopt should
be applicable to particular plant-pesticides that may operate by a
variety of mechanisms. The Agency requests comment on how evidence of
structurally homology for proteinaceous defense compounds could be used
in the future as reliable predictors of functional homology. Would it
be more appropriate to develop an approach that does not rely soley on
percent amino acid sequence homology but also incorporates the
identification of conserved and variable amino acid sequences? For
example, it is postulated that some disease resistance genes encode
transmembrane receptors. Might sequences such as those involved in
transmembrane interactions then be identified to provide additional
assessment of equivalent function?
A number of enzymes such as glucanase, chitinase, and proteinase
inhibitors are also thought to be involved in plant defense responses.
The question then arises as to whether a chitinase from, for example,
tobacco or a microorganism is equivalent to a chitinase found in a
plant sexually compatible with the recipient plant. As in the previous
example, amino acid sequence homology could also assist in establishing
equivalency for these enzymes. However, as with the previous example,
the question of how much homology is sufficient remains. Would a better
measurement be to use stability, substrate specificity, K<SUP>m, and
V<SUP>max? Should these parameters be used in conjunction with
homology?
Nonproteinaceous compounds such as phenolics and phytoalexins are
another class of plant defense compounds. For nonproteinaceous
compounds structure/activity comparisons can be used to determine
functional equivalence. For example, the presence of specific side
chains could be used to establish equivalence. Other parameters such as
stability could also be used. The question for the Agency is what
amount/combinations of information would be necessary to use as a
measure of equivalence..
B. Exemption of Plant-pesticides that Act Primarily by Affecting the
Plant
With regard to its exemption from FIFRA requirements of ``plantpesticides
that act primarily by affecting the plant,'' EPA requests
comment on whether this exemption appropriately focuses the Agency's
regulatory attention on the plant-pesticides likely to present higher
levels of hazard. The Agency also requests comment on whether the
language defining this exemption is sufficiently clear and inclusive to
identify plant-pesticides that act through nontoxic modes of action.
The Agency is considering whether to extend this exemption to
include substances such as plant hormones because they primarily affect
the plant and do not have a directly toxic mechanism of action toward
the target pest. The Agency is requesting comment as to whether it
would be more appropriate to specifically exempt plant hormones as a
category or to include in this exemption a performance-based criterion
based on a description of the characteristics and/or mechanism of
action of hormones (see Unit V.B. of this preamble).
C. Exemption of Coat Proteins from Plant Viruses
EPA is also proposing to exempt from FIFRA regulation, coat
proteins from plant viruses when the coat proteins are produced in
plants. EPA has proposed two options for this exemption with Option 1
presented in the proposed regulatory text. EPA is requesting comment on
the appropriateness and clarity of the two options presented in this
proposal. EPA is also requesting comment on: (1) The potential for the
recipient crop plant producing the viral coat protein to become a weed;
(2) the potential for increased competitive advantage of wild relatives
in their native habitat after cross hybridization with a crop plant
producing a viral coat protein; and (3) the potential for a viral coat
protein gene to recombine with infecting viruses to extend host range
or create new virus diseases.
EPA is considering whether to propose in the future, an exemption
of viral components, other than viral coat proteins, used in viral
resistance strategies in plants. This exemption would include
performance-based criteria that would be used by EPA to determine if a
viral component would be exempt from regulation. EPA is requesting
comment on whether such an exemption would be appropriate and is
requesting comment on criteria that could be used to construct this
exemption.
D. Substantiation of Claims for Confidential Information
EPA requests comment on the proposed requirement (Sec. 174.9 of the
regulatory text) that any claim of confidentiality must be
substantiated at the time the claim is made. Specifically, EPA seeks
comment on how to achieve the best balance between the burden on
industry to provide substantiation before public disclosure becomes an
active issue (e.g., in preparation for FIFRA Science Advisory Panel
meetings) and the regulated community's desire to receive timely
responses on submissions. This balance must take into consideration the
needs of pesticide developers to protect information they believe to be
critical to maintaining their competitiveness and the public's need for
access to information related to potential environmental or human
health effects early enough in the review process to provide informed
comment before EPA makes a decision. EPA encourages the development of
reduced risk pesticides and believes that, given the Agency's
procedural requirements for CBI determinations, without up front
substantiation, timely responses to subsmissions would be difficult
when it becomes necessary to resolve the issue of CBI before a decision
can be made.
VIII. Economic Analysis
The regulatory impact analysis (RIA) evaluates the costs and
benefits of amending EPA's regulations to allow for the regulation or
exemption of specific types of plant-pesticides under FIFRA (40 CFR
152.20 and 40 CFR part 174) and is intended to meet the requirements
for a RIA as established by Executive Order No. 12866, the Regulatory
Flexibility Act, and section 25 of FIFRA.
The RIA presents the alternative regulatory options and the costs
that were considered by the Agency including two options that were
considered by the Agency but not included in this proposal. Four
possible approaches to the regulation of plant-pesticides under FIFRA
were evaluated in the RIA that allowed for varying degrees of
regulatory coverage. RIA Option 1 is the most limited alternative in
regulatory scope. RIA Option 2 represents EPA's proposed, and
preferred, regulatory scope and is broader in coverage than RIA Option
1. In addition to those plant-pesticides regulated under RIA Option 2,
RIA Option 3's scope would include viral coat proteins used as plantpesticides.
Finally, under RIA Option 4, all plant-pesticides,
including those that result from traditional plant breeding, would be
subject to the requirements of FIFRA. The costs of implementing the
four options presented in Unit IV.A. of this preamble are comparable to
each other and correspond to RIA Option 2. The costs for any of the
four options presented in Unit IV.A. are substantially lower than RIA
Option 4.
Generally, costs will depend on whether the Agency exempts a plant
pesticide or whether it requires a registration. The costs of
regulating plant-pesticides are dependent upon the data needed for the
registration of the particular types of plant-pesticides. Data needs
are irrelevant for exempted plant-pesticides. For regulated plant
pesticides, data needs will vary according to the gene product of the
plant-pesticide and the recipient crop.
Aggregate incremental compliance costs to the industry over a 10-
year period under regulatory (RIA) Option 1 are estimated to range from
$53,700 in the first year of implementation to $2.6 million in the 10th
year of implementation, with an average annual revenue requirement
(ARR) of $1.2 million. Under EPA's proposed scope (RIA Option 2),
aggregate incremental compliance costs are predicted to range from
$53,700 in year 1 to $3.1 million in year 10, with an ARR of $1.6
million. Aggregate incremental compliance costs for RIA Option 3 are
estimated at nearly $741,100 in the first year of implementation and
$5.1 million in the 10th year, with an ARR of $2.9 million. Finally,
under RIA Option 4's broad regulatory scope, aggregate incremental
compliance costs are projected to range from $76.6 million in year 1 to
$81 million in year 10, with an ARR of $79 million.
Costs were also estimated for the labor burden that would result
from EPA staff preforming various activities associated with the
registration of plant-pesticides. Some of these activities may include
the establishment of the docket, internal reviews, requests for
additional information, and consultations with applicants. The cost for
the Agency to perform these activities under RIA Option 1 is estimated
to range from nearly $40,000 in year 1 to approximately $259,000 in
year 10. Under EPA's proposed regulatory scope, RIA Option 2, annual
labor burden costs range from approximately $40,000 in the first year
to $391,000 10 years after a final rule is promulgated. For RIA Option
3, EPA costs are estimated to range between $123,000 in year 1 to
$640,000 in year 10. Under the broad regulatory scope of RIA Option 4,
EPA's labor costs are predicted to range between $14.7 million in year
1 to $15.2 million in year 10. Labor burden cost estimates vary by
year, due to the number and type of plant-pesticide submissions the
Agency is predicted to receive.
The aggregate cost to society of the proposed plant-pesticide
regulation is the sum of the total costs to industry, plus the total
costs to the Agency to implement the proposed rule. After calculating
aggregate societal costs, they were discounted to allow for the time
value of money and to determine a constant level annual cost. The
annual societal revenue requirement over the 10-year period of analysis
was estimated at nearly $1.4 million under RIA Option 1, $1.8 million
under RIA Option 2, $3.3 million under RIA Option 3, and $93.7 million
under RIA Option 4.
Primarily affected by this proposed regulation will be those
companies involved with agricultural biotechnology that have been
identified as presently developing and testing plant-pesticides. While
agricultural biotechnology is currently in its infancy with 1993 sales
estimated at less than 2 percent of total biotechnology sales, future
sales are forecasted to grow at an average annual rate of 33 percent to
the year 2003. Firms developing biotechnology products are quite
diverse and include large, multinational corporations, biotechnology
companies (both large and very small), chemical companies, and seed
companies. The impacts of EPA regulation of plant-pesticides to this
growing market sector will not be all negative. Companies involved with
agricultural biotechnology have asked for plant-pesticide regulations
and they stand to benefit tremendously from this proposed regulation.
The proposed rule will generate a wide range of benefits for the
public, the firms involved with agricultural biotechnology, the
environment, nontarget organisms, and states. Registrants of plantpesticides
should benefit from the resolution of uncertainty regarding
regulatory issues. With the promulgation of the proposed regulation,
firms developing and testing plant-pesticides can plan ahead for timely
product development and commercialization which should, in turn,
attract investors to the agricultural biotechnology sector. The
environment will benefit from safety measures that will protect against
unintended environmental effects of accidental and deliberate releases
of genetically engineered organisms. Nontarget organisms, including
endangered species, will benefit from a registration process that will
carefully consider the potential effects that certain plant-pesticides
may have upon them. Finally, states will benefit by having a set of
standardized Federal regulations that will be more easily conveyed,
interpreted, and enforced. Many states may also benefit by not having
to establish their own set of agricultural biotechnology regulations.
Adverse economic impacts from the implementation of the proposed
plant-pesticide regulation are not expected under EPA's proposed scope
(RIA Option 2). Due to the lack of detailed financial information on
those firms that are currently developing and testing plant-pesticides,
the conclusion of ``no adverse economic impacts'' was based on public
and proprietary information provided to EPA by industry financial
advisory groups, biotechnology associations, university biotechnology
specialists, and small biotechnology firms.
IX. Public Record
EPA has established a public record for this rulemaking (docket
control number OPP-300369). The record includes all information
considered by EPA in developing this proposed rule. The record now
includes the following items:
1. Reports of all SAP and BSAC meeting pertaining to this proposed
rule.
2. Support documents and reports, including:
(a) EPA issue paper. FIFRA: Benefit and environmental risk
considerations for inherent plant-pesticides.
(b) EPA issue paper. Issues associated with the regulation of viral
coat proteins under FIFRA and FFDCA.
3. Published literature that is cited in this document.
4. The Regulatory Impact Analysis for this rule.
5. Records of communications between EPA personnel and persons
outside EPA pertaining to the development of this proposed rule. (This
does not include any inter- or intra-agency memoranda, unless
specifically noted in the Index of this docket.)
X. References
(1) EPA issue paper. FIFRA: Benefit and environmental risk
considerations for inherent plant-pesticides.
(2) EPA issue paper. Issues associated with the regulation of viral
coat proteins under FIFRA and FFDCA.
(3) Klaasen, C.D., M.O. Amdur, and J.D. Doull. 1986. Casarett and
Doull's Toxicology: The Basic Science of Poisons. Chapter 2. Third
Edition. Macmillan Publishing Company, New York.
(4) Lamb, C.J., J.A. Ryals, E.R. Ward, and R.A. Dixon. 1992.
Emerging strategies for enhancing crop resistance to microbial
pathogens. Bio/Technology. 10:1436-1445.
(5) Matthews, R.E.F. 1981. Plant Virology. Chap. 17. Second
edition, Academic Press, New York.
(6) Tolin, S.A. 1991. Persistence, establishment, and mitigation of
phytopathogenic viruses. In: Risk Assessment in Genetic Engineering.
Edited by M.A. Levin and H.S. Strauss. McGraw Hill, Inc., New York. pp.
140-161.
XI. Regulatory Assessment Requirements
A. Executive Order 12866
Under Executive Order 12866 (58 FR 51735, October 4, 1993), the
Agency must determine whether the proposed regulatory action is
``significant'' and therefore subject to review by the Office of
Management and Budget (OMB) and the requirements of the Executive
Order. Under section 3(f), the Order defines a ``significant regulatory
action'' as an action that is likely to result in a rule (1) Having an
annual effect on the economy of $100 million or more, or adversely and
materially affecting a sector of the economy, productivity,
competition, jobs, the environment, public health or safety, or State,
local, or tribal governments or communities (also referred to as
``economically significant''); (2) creating serious inconsistency or
otherwise interfering with an action taken or planned by another
agency; (3) materially altering the budgetary impacts of entitlement,
grants, user fees, or loan programs or the rights and obligations of
recipients thereof; or (4) raising novel legal or policy issues arising
out of legal mandates, the President's priorities, or the principles
set forth in this Executive Order.
Pursuant to the terms of this Executive Order, EPA has determined
that this proposed rule is a ``significant regulatory action'' because
it raises novel policy issues arising out of FIFRA legal mandates.
Thus, this proposal will be submitted to OMB for review, and any
comments or changes made in response to OMB suggestions or
recommendations, are documented in the public record.
B. Regulatory Flexibility Act
This proposed rule was reviewed under the provisions of section
3(a) Regulatory Flexibility Act (RFA) [5 U.S.C. 605(b)]. The RFA
requires that agencies take special note of the impact of proposed
regulations on small entities. Analysis requirements under the RFA can
and should be combined with the analysis required under Executive Order
12866.
The regulatory flexibility analysis of this proposed regulation for
plant-pesticides on small entities is demonstrated within the
structuring of the four regulatory options proposed. These options were
considered after extensive evaluations of the benefit/risk tradeoffs
between option cost and risk reduction provided. The Agency has
structured the resulting options from a narrow regulatory scope (RIA
Option 1) to a broad regulatory scope (RIA Option 4) and, as such, has
conducted an ``inherent'' sensitivity analysis for small firms likely
to be affected by this proposed regulation. The Agency has determined
that the tradeoffs between the benefits and risks of the proposed
regulation are optimized under RIA Option 2, EPA's proposed scope.
C. Paperwork Reduction Act Paperwork Reduction Act
The information collection requirements in this proposed rule have
been submitted for approval to the Office of Management and Budget
(OMB) under the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. An
Information Collection Request document has been prepared by EPA (ICR
No. 1693.01) and a copy may be obtained from Sandy Farmer, Information
Policy Branch, (Mail Code 2136), Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460, or by calling (202) 260-2740.
This collection of information has an estimated reporting burden
averaging 1,143 hours per response and an estimated annual
recordkeeping burden averaging 74 hours per respondent. These estimates
include time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and
reviewing the collection of information.
Send comments regarding the burden estimate or any other aspect of
this collection of information, including suggestions for reducing this
burden to Chief, Information Policy Branch, (Mail Code 2136),
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460;
and to the Office of Information and Regulatory Affairs, Office of
Management and Budget, Washington, DC 20503, marked ``Attention: Desk
Officer for EPA.'' The final rule will respond to any OMB or public
comments on the information collection requirements contained in this
proposal.
List of Subjects in Parts 152 and 174
Environmental protection, Biotechnology pesticides, Pesticides and
pests, Plants, Plant-pesticides, Reporting and recordkeeping
requirements.
Dated: November 15, 1994.
Carol M. Browner,
Administrator.
Therefore, it is proposed that 40 CFR Chapter I be amended as
follows:
PART 152--[AMENDED]
1. In part 152:
a. The authority citation for part 152 would continue to read as
follows:
Authority: 7 U.S.C. 136-136y; subpart U is also issued under 31
U.S.C. 9701.
b. In Sec. 152.1, by designating existing text as introductory text
and adding paragraphs (a) and (b) to read as follows:
Sec. 152.1 Scope.
* * * *
(a) For procedures, requirements and criteria applicable to plantpesticides,
refer to part 174 of this chapter.
(b) [Reserved]
c. In Sec. 152.3, by removing all alphabetic paragraph designations
and alphabetically inserting the following definitions to read as
follows:
Sec. 152.3 Definitions.
* * * *
Genetic material necessary for the production means:
(1) Genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance.
(2) Regulatory regions.
It does not include noncoding, nonexpressed nucleotide sequences.
* * * *
Living plant means a plant that is alive, including periods of
dormancy, and all viable plant parts/organs involved in the plant's
life cycle.
* * * *
Noncoding, nonexpressed nucleotide sequences means the nucleotide
sequences are not transcribed and are not involved in gene expression.
Examples of noncoding, nonexpressed nucleotide sequences include
linkers, adapters, homopolymers, and sequences of restriction enzyme
recognition sites.
* * * *
Plant-pesticide means a pesticidal substance that is produced in a
living plant and the genetic material necessary for the production of
the substance, where the substance is intended for use in the living
plant.
Regulatory region means genetic material that controls the
expression of the genetic material that encodes for a pesticidal
substance or leads to the production of a pesticidal substance.
Examples of regulatory regions include promoters, enhancers, and
terminators.
* * * *
d. In Sec. 152.20, by revising paragraph (a)(1) and adding
paragraph (a)(4) to read as follows:
Sec. 152.20 Exemptions for pesticides regulated by another Federal
agency.
* * * *
(a) * * *
(1) Except as provided by paragraphs (a)(3) and (a)(4) of this
section, all biological control agents are exempt from FIFRA
requirements.
* * * *
(4) All plants intended for use as biological control agents and
any portion thereof, except plant-pesticides, are exempt from the
requirements of FIFRA. Plant-pesticides are addressed in part 174,
subpart A, of this chapter.
* * * *
By adding part 174 to read as follows:
PART 174--PROCEDURES AND REQUIREMENTS FOR PLANT-PESTICIDES
Subpart A--General Provisions
Sec.
174.1 Scope and purpose.
174.3 Definitions.
174.5 Scope of coverage.
174.7 Submission of information regarding potential unreasonable
adverse effects.
174.9 Confidential business information claims for plantpesticide
submissions.
Subpart B--[Reserved]
Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a and 371.
Subpart A--General Provisions
Sec. 174.1 Scope and purpose.
Pesticidal substances produced in plants are pesticides as defined
in FIFRA section 2. The characteristics of these pesticides such as
their production and use in plants, their biological properties, and
their ability to spread and increase in quantity in the environment
distinguishes them from traditional, chemical pesticides. Therefore,
plant-pesticides are subject to different regulatory requirements and
procedures than traditional, chemical pesticides. This part 174 sets
forth regulatory requirements, criteria, and procedures applicable to
plant-pesticides under FIFRA and FFDCA. Unless otherwise provided by
this part, the regulations in parts 152 through 173 and parts 177
through 186 of this chapter, where applicable, apply to plantpesticides.
EPA recognizes the unique nature of plant-pesticides
necessitates flexibility in the application of regulations designed for
traditional pesticides to plant-pesticides.
Sec. 174.3 Definitions.
Terms used in this part have the same meaning as in FIFRA. In
addition, the following terms have the meaning set forth in this
section.
Active ingredient, when referring to plant-pesticides only, means a
pesticidal substance that is produced in a living plant and the genetic
material necessary for the production of the substance, where the
substance is intended for use in the living plant.
Administrator means the Administrator of the United States
Environmental Protection Agency or his/her delegate.
Biological control agent means any living organism applied to or
introduced into the environment that is intended to function as a
pesticide against another organism declared to be a pest by the
Administrator.
Bridging crosses between plants means the utilization of an
intermediate plant in a cross to produce a viable zygote between the
intermediate plant and a first plant, in order to cross the plant
resulting from that zygote with a third plant that would not otherwise
be able to produce viable zygotes from the fusion of its gametes with
those of the first plant. The result of the bridging cross is the
mixing of genetic material of the first and third plant through the
formation of an intermediate zygote.
EPA means the United States Environmental Protection Agency unless
otherwise specified.
FFDCA means the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321
et seq.)
FIFRA means the Federal Insecticide, Fungicide, and Rodenticide
Act, as amended (7 U.S.C. 136-136y).
Genetic material necessary for the production means:
(1) Genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance.
(2) Regulatory regions.
It does not include noncoding, nonexpressed nucleotide sequences.
Genetic material that encodes for a pesticidal substance or leads
to the production of a pesticidal substance does not include regulatory
regions or noncoding, nonexpressed nucleotide sequences.
Inert ingredient, when referring to plant-pesticides only, means
any substance, such as a selectable marker, other than the active
ingredient, and the genetic material necessary for the production of
the substance, that is intentionally introduced into a living plant
along with the active ingredient, where the substance is used to
confirm or ensure the presence of the active ingredient.
Living plant means a plant that is alive, including periods of
dormancy, and all viable plant parts/organs involved in the plant's
life cycle.
Noncoding, nonexpressed nucleotide sequences means the nucleotide
sequences are not transcribed and are not involved in gene expression.
Examples of noncoding, nonexpressed nucleotide sequences include
linkers, adapters, homopolymers, and sequences of restriction enzyme
recognition sites.
Pesticide means any substance or mixture of substances intended for
preventing, destroying, repelling, or mitigating any pest, or intended
for use as a plant regulator, defoliant, or desiccant, other than any
article that:
(1) Is a new animal drug under FFDCA section 201 (w); or
(2) Is an animal drug that has been determined by regulation of the
Secretary of Health and Human Services not to be a new animal drug; or
(3) Is an animal feed under FFDCA section 201(x) that bears or
contains any substances described by Sec. 152.3(s)(1) or (2) of this
chapter.
Plant-pesticide means a pesticidal substance that is produced in a
living plant and the genetic material necessary for the production of
the substance, where the substance is intended for use in the living
plant.
Recipient plant means the plant into which the plant-pesticide is
introduced and in which the plant-pesticide is produced.
Regulatory region means genetic material that controls the
expression of the genetic material that encodes for a pesticidal
substance or leads to the production of a pesticidal substance.
Examples of regulatory regions include promoters, enhancers, and
terminators.
Sexually compatible, when referring to plants, means capable of
forming a viable zygote through the fusion of two gametes, including
the use of bridging crosses or wide crosses between plants.
Source means the donor of the genetic material that encodes for a
pesticidal substance or leads to the production of a pesticidal
substance.
Wide crosses between plants means to facilitate the formation of
viable zygotes through the use of surgical alteration of the plant
pistil, bud pollination, mentor pollen, immunosuppressants, in vitro
fertilization, pre- and post-pollination hormone treatments,
manipulation of chromosome numbers, embryo culture, or ovary and ovule
cultures or any other technique that the Administrator determines meets
this definition.
Sec. 174.5 Scope of coverage.
(a) Plant-pesticides not exempt from the requirements of FIFRA
under paragraph (b) of this section are subject to the requirements of
FIFRA.
(b) All plant-pesticides (both the pesticidal substance and the
genetic material necessary for its production) meeting at least one of
the following criteria are exempt from the requirements of FIFRA:
(1) The genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance is derived from
plants that are sexually compatible with the recipient plant and has
never been derived from a source that is not sexually compatible with
the recipient plant.
(2) The pesticidal substance acts primarily by affecting the plant
so that the target pest is inhibited from attaching to the plant,
penetrating the plant, or invading the plant's tissue in at least one
of the following ways:
(i) The pesticidal substance acts as a structural barrier to
attachment of the pest to the host plant, a structural barrier to
penetration of the pest into the host plant, or a structural barrier to
spread of the pest in the host plant, for example, through the
production of wax or lignin, or length of trichomes (plant hairs).
(ii) The pesticidal substance acts in the host plant to inactivate
or resist toxins or other disease-causing substances produced by the
target pest.
(iii) The pesticidal substance acts by creating a deficiency of a
plant nutrient or chemical component essential for pest growth on/in
the host plant.
(3) The pesticidal substance is a coat protein from a plant virus.
Sec. 174.7 Submission of information regarding potential unreasonable
adverse effects.
Any person who sells or distributes any plant-pesticide exempt
under Sec. 174.5 who obtains any information regarding potential
unreasonable adverse effects on human health or the environment must
within 30 days of receipt of such information submit the information to
EPA, unless the person has actual knowledge that EPA has been
adequately informed of such information.
Sec. 174.9 Confidential business information claims for plantpesticide
submissions.
Although it is strongly recommended that the submitter minimize the
amount of data and other information claimed as CBI, a submitter may
assert a claim of confidentiality for all or part of the information
submitted to EPA in a submission for a plant-pesticide. (See part 2,
subpart B, of this chapter.) To assert such a claim, the submitter must
comply with the following procedures:
(a) Any claim of confidentiality must accompany the information at
the time the information is submitted to EPA. Failure to assert a claim
at that time will be considered a waiver of confidentiality for the
information submitted, and the information may be made available to the
public, subject to section 10(g) of FIFRA, with no further notice to
the submitter.
(b) Any claim of confidentiality must be accompanied, at the time
the claim is made, by comments substantiating the claim and explaining
why the submitter believes that the information should not be
disclosed. The submitter should refer to Sec. 2.205(e)(4) of this
chapter for points to address in the substantiation. If such comments
are marked confidential when submitted to EPA, they will be treated as
such in accordance with Sec. 2.205(c) of this chapter. EPA will
consider incomplete all plant-pesticide submissions containing
information claimed as CBI that are not accompanied by substantiation,
and will suspend the review period of such submissions until the
required substantiation is provided.
Subpart B--[Reserved]
[FR Doc. 94-28822 Filed 11-22-94; 8:45 am]
BILLING CODE 6560-50-F
