[Federal Register Volume 59, Number 225 (Wednesday, November 23, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-28823]
[[Page Unknown]]
[Federal Register: November 23, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300368; FRL-4758-8]
RIN 2070-AC02
Plant-Pesticides; Proposed Exemption From the Requirement of a
Tolerance Under the Federal Food, Drug, and Cosmetic Act
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: This document proposes an exemption from the requirement of a
tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA) for
specific categories of pesticidal substances produced by plants to
protect them against pests and disease. Pesticidal substances produced
by plants, along with the genetic material necessary for the production
of these substances, have been designated ``plant-pesticides'' by the
Agency. The categories of plant-pesticides EPA is proposing to exempt
from the requirement of a tolerance are based upon evaluation of the
potential for new dietary exposures to these pesticidal substances when
they are produced in plants or plant parts used as raw agricultural
commodities. EPA believes that a tolerance for these categories of
plant-pesticides is not necessary to protect the public health.
DATES: Comments identified by the docket control number [OPP-300368]
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 22202.
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
Substances that are produced in plants to enable the plants to
resist pests or disease are pesticides under section 2 of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) (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 breeding or through the techniques
of modern biotechnology. These substances, along with the genetic
material necessary to produce the substances, are designated by the
Agency as ``plant-pesticides.''
There are a number of types of substances that are produced in
plants to protect them against pest attack and disease. For example,
phytoalexins (plant-produced substances that act against microbial
phytopathogens) could be considered plant-pesticides because of their
role in plant resistance to plant pests. These substances are examples
of plant-pesticides that can be introduced into a plant through
traditional breeding. Another example of a plant-pesticide is an
insecticidal delta endotoxin from the bacterium, Bacillus
thuringiensis, introduced into plants through biotechnology techniques
to impart or enhance resistance to insect pests.
In the past, EPA has addressed, under FFDCA, how it regulates
substances that are extracted from plants and used as pesticides on
food or feed. For example, a tolerance has been set for pyrethrum that
is extracted from plants and applied to food or feed. However, until
now, the Agency has not clearly explained how it intends to regulate
pesticidal substances produced in plants and not extracted from the
plant (``plant-pesticides'') under FFDCA. For example, if a food plant
could be modified, for pesticidal purposes, to produce pyrethrum, EPA
has not explained how this pyrethrum would be regulated under FFDCA.
The Agency is proposing to exempt certain categories of plant-
pesticides that the Agency believes would not result in new dietary
exposures (e.g., not significantly different from what humans are
currently exposed to in the food supply) and therefore do not require
the establishment of a tolerance to protect the public health. There
are circumstances where EPA believes that plant-pesticides should be
regulated by EPA for the purpose of either setting a tolerance or
issuing a specific exemption from the requirement of a tolerance for a
particular plant-pesticide. In general, plant-pesticides that would
result in significantly new or different dietary exposures would be
subject to EPA review under FFDCA tolerance procedures. These
categories of plant-pesticides would not be exempt from the requirement
of a tolerance under this proposal.
This proposed rule, is one of several documents published in
today's Federal Register that address EPA's regulation of plant-
pesticides. The other notices are: (1) A proposed policy statement that
generally describes how EPA proposes to regulate plant-pesticides under
the FIFRA and 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 regulatory
amendment that would describe categories of plant-pesticides that are
subject to or exempt from regulation under FIFRA and clarifies the
status of plants that produce plant-pesticides (``Plant-pesticides
Subject to the Federal Insecticide, Fungicide, and Rodenticide Act;
Proposed Rule''); (3) a proposed exemption from the requirement of a
tolerance under FFDCA for viral coat proteins (``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 under FFDCA for nucleic acids, including deoxyribonucleic and
ribonucleic acids (``Plant-pesticides; Proposed Exemption from the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act for Nucleic Acids Produced in Plants''). A plant-pesticide would be
defined 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. The
definition of the active ingredient for plant-pesticide would be the
same as the definition for plant-pesticide (see Federal Register
document entitled, ``Plant-pesticides Subject to the Federal
Insecticide, Fungicide, and Rodenticide Act; Proposed Rule'').
This proposal addresses only the component of plant-pesticides
comprising the pesticidal substance produced in food plants. The
component comprising the genetic material necessary for the production
of these substances is addressed in another proposed exemption from the
requirement of a tolerance for nucleic acids produced in plants as part
of a plant-pesticide (see the Federal Register document entitled,
``Plant-pesticides; Proposed Exemption from the Requirement of a
Tolerance Under the Federal Food, Drug, and Cosmetic Act for Nucleic
Acids Produced in Plants'').
II. Statutory Authority
This exemption from the requirement of tolerance is being proposed
under the authority of section 408(c) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321 et. seq.). The reorganization plan of 1970
reallocated the authority under FFDCA to regulate pesticide residues in
foods and animal feeds to EPA. Under FFDCA section 408, pesticide
chemicals added to a raw agricultural commodity, that are not
``generally recognized as safe'' (GRAS), are deemed to be unsafe unless
a tolerance, or an exemption from the requirement of a tolerance, for
such pesticide residues is established and the pesticide residue is
within the tolerance limits. Section 408 of the FFDCA applies to all
``pesticide chemicals'' which are defined in section 201(q) of the
FFDCA as:
any substance which, alone, in chemical combination or in
formulation with one or more other substance, is ``a pesticide''
within the meaning of [FIFRA] . . .and which is used in the
production, storage, or transportation of raw agricultural
commodities.
Under FFDCA section 408(c), EPA can exempt, by regulation, any
pesticidal chemical from the necessity of a tolerance when such
tolerance is not necessary to protect the public health. The result of
such an exemption is also to authorize residues of the pesticidal
chemical in any processed foods made from the raw agricultural
commodity that contain the residue as a result of the pesticide on the
raw agricultural commodity.
III. Proposed Exemptions
In developing this proposal, EPA identified three categories of
plant-pesticides that can be produced in recipient food plants where
the recipient food plant would be defined as the plant into which the
plant-pesticide is introduced and in which the plant-pesticide is
produced. The three categories of plant-pesticides are: (1) Plant-
pesticides that are derived from food or non-food plants that are
closely related to the recipient plant; (2) plant-pesticides that are
derived from food plants that are not closely related to the recipient
food plant and that would not result in significantly different dietary
exposures when produced in the recipient food plant; and (3) plant-
pesticides either derived from nonfood plants that are not closely
related to the recipient plant or derived from a nonplant source. EPA
is proposing to exempt from the requirement of a tolerance plant-
pesticides in categories (1) and (2) above and these are defined in the
proposed regulatory text. In the preamble of this document, these two
categories are described in Units III.A. and III.B., respectively and
analyzed in Unit III.D. Plant-pesticides in category (3) above would
not be exempt from the requirement of a tolerance under this proposal.
A. Category 1: Exemption of Plant-pesticides Derived from Closely
Related Plants
This exemption is based upon the premise that new dietary exposures
would not likely arise for plant-pesticides produced in recipient food
plants if the genetic material leading to the production of the
pesticidal substance is derived from closely related plants.
For the purposes of describing this category of plant-pesticides,
EPA is presenting three options for a standard based on the relatedness
of plants. These options are described in Unit III.A. with the analysis
of the options in Unit III.D. of this preamble. The Agency's aim when
it selects one of these approaches for its final rule is to: (1)
Distinguish, on a risk basis, those plant-pesticides that would result
in new dietary exposures from those that would not; (2) provide 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; and (3) create as similar a scope of regulation
as possible under FFDCA and FIFRA given the differences in mandate and
structure of the two statutes. (See ``Plant-pesticides Subject to the
Federal Insecticide, Fungicide, and Rodenticide Act; Proposed Rule''
for details on the scope options proposed under FIFRA.) Note, that some
options offered in the proposed rule under FIFRA are not offered in
this proposed regulation under FFDCA because EPA believes that they
would not be appropriate for describing a category of plant-pesticides
that would not present new dietary exposures. The options that are not
discussed under FFDCA are not EPA's preferred option under FIFRA.
1. Option 1: Plant-pesticides derived from sexually compatible
plants. The preferred approach EPA is proposing to use, in establishing
this exemption, is based on the concept of sexual compatibility as a
measure of relatedness between plants. The use of the standard of
sexual compatibility is embodied in the following language from the
proposed regulatory text:
Residues of pesticidal substances produced in living plants as
plant-pesticides are exempt from the requirement of a tolerance 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 or from sexually compatible plants. The standard under this
option would rely primarily on the taxonomic grouping of genus and
would exempt from the requirement of a tolerance plant-pesticides that
are moved between source and recipient plants that are in the same
genus. The assumption underlying this approach is that this grouping
correlates to a relatively high degree of relatedness even though not
all plants in a genus are sexually compatible. For example, traits
ranging from flower morphology to the presence of particular alkaloids
and flavonoids have been used to determine whether to classify a plant
species in a particular genus. Recognizing that some plants that are
sexually compatible are classified in different genera and assuming
that sexual compatibility correlates with 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. [Residues of pesticidal substances produced
in living plants as plant-pesticides are exempt from the requirement of
a tolerance 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.
B. Category 2: Plant-pesticides Derived from Food Plants that are Not
Closely Related to the Recipient Plant
There are circumstances where experience with exposure can be
inferred for plant-pesticides introduced into food plants from other
food plants that are not closely related to the recipient plant. For
plant-pesticides derived from a food plant that is not closely related
to the recipient food plant, there is experience with exposure because
both plants have contributed to the food supply. Thus, the Agency is
proposing to exempt from the requirement of a tolerance plant-
pesticides derived from food plants that are not closely related to the
recipient plant, if there would not be significantly different dietary
exposures when the plant-pesticide is produced in the recipient food
plant. The criteria defining this exemption are as follows:
Residues of pesticidal substances produced in living plants as
plant-pesticides are exempt from the requirement of a tolerance when
the genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance is derived from
plants that are not sexually compatible with the recipient plant if:
(1) The genetic material that encodes for a pesticidal substance
or leads to the production of a pesticidal substance is derived from
food plants; and
(2) The pesticidal substance would not result in significantly
different dietary exposures.
C. Terms Used
The following are terms used in the two options for the Category 1
exemption presented in Unit III.A. and the Category 2 exemption
presented in Unit III.B. of this preamble.
The phrase ``the genetic material that encodes for a pesticidal
substance or leads to the production of a pesticidal substance'' refers
to genetic material that directly encodes for the production of a
pesticidal substance or encodes 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. 2). For the purposes of this exemption under FFDCA,
this phrase is not intended to include regulatory regions or noncoding,
nonexpressed nucleotide sequences when the gene would otherwise be
exempt. For the exemptions proposed in this document, these regulatory
regions and noncoding, nonexpressed nucleotide sequences may be derived
from any source. For example, if a viral promoter attached to a corn
gene encoding a pesticidal substance is introduced into another corn
variety, the gene and the viral promotor genetic construct would meet
the criteria of these exemptions.
The definition for ``sexually compatible'' would mean being capable
of forming a viable zygote through the fusion of two gametes and can
include the use of bridging crosses and the use of wide cross breeding
techniques of surgical alteration of the plant pistol, bud pollination,
mentor pollen, immunosuppressants, in vitro fertilization, pre- and
post- pollination hormone treatments, manipulation of chromosome
numbers, and embryo culture. Wide crosses, for the purpose of this
exemption, also include 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, ``. . .result in significantly different dietary
exposure. . .'' relates only to the Category 2 exemption and would
mean:
(1) The pesticidal substance is produced in inedible portions of
the source food plant, but, in the recipient plant, the pesticidal
substance is present in the plant's edible portions;
(2) The pesticidal substance is produced in the immature, but
not in the mature, edible portions of the source food plant, but, in
the recipient plant, the pesticidal substance is present in the
mature, edible portions;
(3) The pesticidal substance is from a source food plant
normally cooked or processed prior to consumption and is produced in
a recipient plant that is not normally cooked or processed prior to
consumption;
(4) The pesticidal substance is derived from a source food plant
that is not a major crop for dietary consumption and is introduced
into a recipient plant that is a major crop for dietary consumption.
The ``source food plant'' is the donor of the genetic material that
encodes for a pesticidal substance or leads to the production of a
pesticidal substance.
The phrase ``. . .has never been derived from a source plant that
is not sexually compatible to the recipient plant. . .'' (Category 1)
is meant to indicate in the proposed regulatory text that the plant-
pesticide would not qualify for the exemption in this proposal if the
genetic material, for example, 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 plants subsequently hybridized using wide
cross techniques with rye to produce triticale. The endotoxin produced
in the triticale would not be eligible for the exemption.
D. Analysis of Exemptions
This unit contains analysis of the two options presented in Unit
III.A., the exemption presented in Unit III.B., and the relationship
between the options in Unit III.A. and the exemption in Unit III.B. of
this preamble.
1. Analysis of options for category 1 exemption presented in Unit
III.A. Under FFDCA, the options must be examined specifically within
the context of the food supply and dietary consumption. Many substances
having pesticidal activity occur naturally at low concentrations in the
edible parts of plants and have long been accepted as part of the human
diet. Extensive use and experience show the safety of foods containing
these substances. For many foods, the naturally occurring toxicants
they may contain, including pesticidal substances, are known (Ref. 1).
Also, the established practices that plant breeders employ in selecting
and developing new plant varieties, such as chemical analyses, taste-
testing, and visual analyses, have historically proven to be reliable
for ensuring food safety. That there are few examples of new plant
varieties causing food safety concerns, despite the large numbers of
new varieties introduced into commerce each year, is a reflection of
the effectiveness of this process.
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 using controlled crosses to produce plant
hybrids has 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. Sexually compatible crop
varieties are also crossed with each other to achieve better pest
resistance in their progeny.
EPA believes, based on this experience, that most plant varieties
developed by plant breeders using genetic material from plants that
meet the sexually compatible standard produce food that is safe for
human consumption and/or that appropriate processing procedures are
widely known and routinely used by consumers in preparation of food
from such sources.
A plant-pesticide would meet the criteria of this standard if the
plants that are used as genetic donors are not themselves food plants,
as long as they are sexually compatible with the recipient food plant
that is producing the plant-pesticide. It has been common agricultural
practice to introduce traits from sexually compatible wild relatives
into plant varieties to be used as food plants. These wild, sexually
compatible relatives of cultivated plants do not have any history of
human consumption but have safely contributed traits through sexual
recombination to cultivars on the market. Food plant varieties
developed in this way have been introduced and consumed by humans for
many years with no observed adverse affects. For example, under this
standard, a wild species related to tomato may be used as a source of
genetic material in developing a cultivated tomato variety.
EPA proposes to extend the concept of sexual compatibility to
include wide crosses because wide crosses are commonly used to expand
the gene pool for varietal improvement, and EPA believes that the use
of wide crosses to produce a viable zygote indicates a fairly high
degree of relatedness and thus a high probability that the parental
plants have common constitutions. 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 to define, for
the purposes of this rulemaking, wide crosses based on existing
techniques, with a provision to add to the definition as the
Administrator determines is appropriate.
As described in Unit III.A. of this preamble, EPA is considering a
second option for describing relatedness based primarily on the
taxonomic standard of genus rather than on sexual compatibility alone.
Under this approach, a plant-pesticide would be exempt if the genetic
material encoding for a pesticidal substance or leading to the
production of a pesticidal substance is derived from a plant within the
same genus as the recipient plant. EPA recognizes that some plants that
are closely related (as evidenced by sexual compatibility) are not
classified in the same genus. Under this second option, EPA would
extend the exemption to plant-pesticides derived from plants sexually
compatible with the recipient plant, as well as to intrageneric plant-
pesticides.
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 most likely occurred and reinforced 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., wide crosses) is evidence that
such plants are fairly closely related and share a common constitution.
The majority of successful wide crosses and bridging crosses to date
have occurred between species within the same genus.
However, taxonomy of plant genera may be an artificial standard
within the context of the food supply since there may be species within
any given genus that are not used as food or may not have contributed
traits to food through breeding and thus experience with their risks
may not exist. In addition, the experience base (e.g., experience with
whether or not naturally occurring toxicants are present) for most of
the species within most genera is more limited than for those species
comprising the major food crops.
Under Option 1, a plant-pesticide produced from genetic material
derived from a plant in the same genus as, but not sexually compatible
with, the recipient plant would not qualify for the exemption. In
contrast, under Option 2, this plant-pesticide would qualify for the
exemption. It is, therefore, possible under Option 2 for a plant-
pesticide to be exempt from the requirement of a tolerance without the
base of experience that breeders have for sexually compatible plants.
Finally, none of the options 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 no longer be considered
by the Agency to be ``derived from the source plant.'' 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 that in the source plant and these
would not be exempt. If this type of modification were to occur, the
base of experience for that plant-pesticide in food would no longer be
relevant.
2. Analysis of Category 2 exemption presented in Unit III.B. Based
on the experience with food plants, conclusions as to dietary safety of
these foods can be drawn. EPA has concluded that an exemption from the
requirement of a tolerance is appropriate for certain pesticidal
substances produced from genetic material derived from food plants that
are not close relatives to the recipient plant producing the plant-
pesticide if there will not be significantly different human dietary
exposures. The Agency has defined a set of criteria to determine
whether significantly different dietary exposures from the these plant-
pesticides would occur. For example, if a pesticidal substance is
normally only produced in inedible portions or immature fruit of the
food plant, the Agency would require a tolerance review if the modified
food plant were to produce that substance in its mature fruit or edible
portions. For example, tomatine is a toxicant produced in much higher
amounts in immature tomato fruit (that is normally not eaten) than it
is in the mature fruit. If the genetic material leading to the
production of tomatine were introduced into a plant for pesticidal
purposes such that the tomatine were produced in the mature fruit as it
is in the immature fruit, EPA would need to conduct a tolerance review
to determine whether a tolerance is necessary to protect the public
health. Similarly, if a pesticidal substance is produced in a food that
is almost always cooked or processed prior to consumption, the Agency
would want to conduct a tolerance review if another food plant that is
not cooked or processed prior to consumption is modified to produce the
substance. For example, some beans are rich in lectins, glycoproteins
that are natural toxicants. Soaking and cooking the beans destroys the
lectin. If the genetic material encoding for the lectin were
transferred, for pesticidal purposes, from beans to a plant which is
not normally cooked (e.g., lettuce), EPA would need to conduct a
tolerance review. A significantly different dietary exposure could also
result if a widely consumed food staple such as corn is modified to
produce a pesticidal substance from a food crop with minor consumption
such as eggplant.
EPA is also considering adding another criterion to the exemption
from the requirement of a tolerance for categories of plant-pesticides
that would not result in significantly different dietary exposures (see
Unit III.B. of this preamble). This criterion would address the
potential for allergenicity of plant-pesticides in food. Under this
criterion, if a plant-pesticide is derived from a commonly allergenic
food, the plant-pesticide would not be exempt from tolerance
requirements and the Agency would conduct a tolerance review on a case-
by-case basis to determine whether to establish an exemption from the
requirement of a tolerance, establish a tolerance, or deny a tolerance.
Some examples of foods that commonly cause an allergenic response are
milk, eggs, fish, crustacea, molluscs, tree nuts, wheat, and legumes
(particularly peanuts and soybeans).
3. Analysis of the relationship between the options for the
Category 1 exemption in Unit III.A and the Category 2 exemption in Unit
III.B. Option 2 discussed in Unit III.A. of this preamble has different
implications for the exemption described in Unit III.B. of this
preamble than does Option 1 in Unit III.A. If the concept in the Unit
III.B. exemption were transcribed to fit with Option 2, a distinction
would be drawn between plant-pesticides derived from food plants in the
same genus as the recipient plant but not sexually compatible with the
recipient plant, and plant-pesticides derived from food plants outside
the same genus as the recipient plants and also not sexually compatible
with the recipient plant. This distinction may be somewhat artificial
under FFDCA since it is based on a taxonomic standard rather than one
of experience with dietary exposure. The Unit III.B. exemption would
read as follows if it were coupled with Option 2:
Residues of pesticidal substances produced in plants that are
not in the same genus as the recipient plants are exempt from the
requirement of a tolerance if:
(1) the genetic material that encodes for a pesticidal substance
or leads to the production of a pesticidal substance is derived from
food plants and
(2) the pesticidal substances would not result in significantly
different dietary exposures.
``Significantly different dietary exposures'' would be defined as
in Unit III.C. of this preamble.
Modifying the exemption in Unit III.B. in such a way raises the
following specific question. Should EPA treat plant-pesticides derived
from sexually incompatible food plants outside the genus of the
recipient plant differently from plant-pesticides derived from sexually
incompatible food plants within that genus? In the first case, the
plant-pesticide (produced from genetic material derived from sexually
incompatible food plants outside the genus of the recipient plant)
would have to meet certain criteria to qualify for an exemption. In the
latter case, the plant-pesticide (produced from genetic material
derived from sexually incompatible food plants within the genus of the
recipient plant) would be exempt unconditionally from the requirement
of a tolerance (i.e., without any conditional criteria describing
``significantly different dietary exposure''). The base of experience
in relation to food safety may not justify not applying these criteria
to sexually incompatible food plants within the same genus as the
recipient plant. In addition, greater confusion concerning the status
of a particular plant-pesticide may arise under the Option 2/
transcribed Unit III.B. exemption than with the Option 1/Unit III.B.
exemption.
IV. External Review
In developing its approach to plant-pesticides under FFDCA, EPA
requested the advice of two scientific advisory committees on FFDCA
related issues. On July 13, 1993, EPA requested the advice of a
Subcommittee of the EPA Biotechnology Science Advisory Committee (BSAC)
on a series of scientific questions dealing with EPA's approach under
the FFDCA. On January 21, 1994, a joint meeting of a Subpanel of the
FIFRA Scientific Advisory Panel (SAP) and BSAC was held and EPA asked
advice from this joint Subpanel on EPA's approach under FFDCA. The
primary goal of the questions posed at both meetings was to identify,
for regulatory purposes, those circumstances in which new or
significantly different human dietary exposures to plant-pesticides
could occur. The reports from these meetings are available in the
public docket for this proposed rule.
At the July 13, 1993, meeting the Agency questioned the
subcommittee on: what information exists on which plant-pesticides in
food might be of concern should their levels be significantly increased
via breeding or via engineering methodologies; whether information
exists on exposure in the diet to levels of plant-pesticides in raw
agricultural commodities; and how plant breeders ensure that natural
plant toxicants do not exceed acceptable levels in foods.
The Subcommittee said:
``Breeders depend primarily on familiarity with food crops
(e.g., knowledge of which crop plants have the ability to produce
which toxicants) to ensure the safety of food from the various crop
plant varieties. If the plant species is known to possess the
ability to produce a toxicant (e.g., potato plants can express
solanine), new varieties of the plant are tested for toxicant
content (e.g., potato varieties are tested for alkaloid content). At
this time, most of this knowledge is part of breeders' experience;
no formal, complete data bases exist.''
However, the Subcommittee believed that in light of breeders'
experience and familiarity with the characteristics of crop plants and
their sexually compatible relatives, the screening procedures employed
in traditional breeding and known food processing considerations,
plant-pesticides under certain conditions could be exempted from
regulatory oversight. The Subcommittee suggested the following scheme
to identify those groupings wherein plant-pesticides might present new
and novel exposures. They suggested that:
(1) Plant pesticides in plants commonly consumed by humans as
food be exempt as long as the plant's genetic material is derived
from related plants within the same family that have contributed
traits to the food plant through the mechanism of sexual
recombination (including wide crosses and embryo rescue).
(2) Plant pesticides in plants in which the genetic material is
derived from plants commonly used as food, but which are not members
of the same family would be subject to review if one or more of the
following criteria are met:
(a) The pesticidal substance, normally produced in the inedible
portions of the source food plant, is present in the edible portions
of the modified host plant.
(b) The pesticidal substance, derived from a source food plant
almost always cooked or processed, is introduced into a food plant
that is not cooked or processed prior to consumption.
(c) The pesticidal substance is derived from a minor food crop
and introduced into a major food crop.
(3) Any pesticidal substance intentionally modified to have a
significantly different structure, function or composition from that
known to exist in food would require a food tolerance determination
by the Agency.
(4) Any pesticidal substance introduced into a food plant and
derived from a source not used as food, except as described in (1)
above, would require review under FFDCA.
At the January 21, 1994, joint SAP/BSAC Subpanel meeting, the use
of sexual compatibility (and thus sexual recombination) and/or taxonomy
as a standard for the potential for significantly different dietary
exposures was once again discussed. In response to the question of
whether plants in a sexually compatible population are likely to share
many substances or traits, the joint Subpanel agreed that sexually
compatible plants are more likely to have a common constitution than
unrelated plants and thus are less likely to lead to novel exposures.
They noted that 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 exposures, the joint Subpanel 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 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 plant-
pesticides 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., Category 1 and 2 exemptions; see Units III.A. and III.B. of this
preamble).
EPA's response: EPA has utilized the suggestions of the BSAC
Subcommittee and joint SAP/BSAC Subpanel in developing this proposal.
In particular, EPA has utilized the concepts put forth by the advisory
committees in developing the language of the Agency's preferred
approaches. EPA also used the advice in developing the alternative
options.
EPA captured in Option 1 in Unit III.A. of this preamble the
concept of exempting from tolerance requirements plant-pesticides
derived from plants sexually compatible with the recipient plants as
suggested by the first part of a two part recommendation of the BSAC
subcommittee at the July 13, 1993, meeting; the BSAC subcommittee
suggested exemption of plant-pesticides from ``related plants within
the same family that have contributed traits to the food plant through
the mechanism of sexual recombination (including wide crosses and
embryo rescue).'' This approach was reaffirmed at the January 21, 1994,
joint SAP/BSAC meeting.
The Agency, in creating the approach described in Unit III.B. of
this preamble, essentially captured the second half of the scheme
suggested by the BSAC subcommittee at the July 13, 1993, meeting; i.e.,
that under certain conditions plant-pesticides encoded by genetic
material from food plants that are not sexually compatible can be
exempt.
In terms of the alternative option, at the January 1994 meeting,
the concept of ``genus'' as a criterion of relatedness between plants
was confirmed, and EPA used that concept to create Option 2 of Unit
III.A. of this preamble.
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 plant-
pesticides 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 III. 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 V. of this preamble).
V. Request for Comment
The Agency requests comments on whether EPA has appropriately
identified in this proposed exemption from the requirement of a
tolerance those plant-pesticides that are not likely to result in new
dietary exposures. EPA proposes to exempt from the requirement of a
tolerance under FFDCA: (1) Plant-pesticides derived from closely
related plants and (2) under certain conditions, plant-pesticides
derived from food plants that are not sexually compatible with the
recipient food plant because EPA believes tolerances for these plant-
pesticides are not necessary to protect the public health.
Under the first exemption (Category 1), EPA has described two
options, with Option 1 presented in the proposed regulatory text. EPA
requests comments on these three options, specifically as to whether
they appropriately identify, plant-pesticides that would not result in
new dietary exposures and whether the language it uses in the two
options to define this grouping for regulatory purposes is clear. EPA
also requests comments on which option is most appropriate and why.
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 IV. of this preamble). EPA also requests comment on whether
the group of plant-pesticides that would be regulated under this
approach would be equivalent to the group of plant-pesticides that
would be regulated under Options 1, or 2.
EPA requests comments on whether it has appropriately identified in
the second exemption (Category 2) those plant-pesticides that should
not be exempted because significantly different dietary exposures could
occur from plant-pesticides derived from food plants not closely
related to the recipient plant (i.e., substances produced in inedible
portions of source plants but in edible portions of recipient plant, in
immature fruits of source plant but in mature fruits of recipient
plant, derived from plants normally cooked or processed before
consumption and introduced into a plant not normally processed or
cooked, or derived from a crop that is not a major crop for human
dietary consumption and introduced into a major crop). EPA requests
comment on whether the language it used to describe these criteria is
sufficiently clear. It requests comment on whether cereal grains would
be an appropriate category to be included in the definition of ``major
crops for human dietary consumption.'' EPA also recognizes that some
crops are highly consumed by children but not by the rest of the
population and requests comment on whether these criteria adequately
address categories of crops that are highly consumed by children.
The Agency also specifically requests comment on whether it should
include, as a qualification to the second exemption (Category 2) a
criterion restricting the possibility that a breeder might take a
plant-pesticide derived from a non-food plant and introduce it into a
sexually compatible food plant (under the Category 1 exemption
described in Unit III.A. of this preamble) and then subsequently move
the plant-pesticide into a sexually incompatible food plant (under the
Category 2 exemption described in Unit III.B. of this preamble). By
bridging these two exemptions, breeders might take a plant-pesticide
from a wild relative which is never eaten and introduce it into another
crop that is not sexually compatible to the wild relative. The Agency
is also requesting comment on whether this would be more critical to
Option 1 or Option 2. The Agency is also requesting comment on whether,
for the Category 2 exemption, a qualification should be included
restricting the possibility that a plant-pesticide from a nonplant
source, such as Bacillus thuringiensis, is introduced into a food plant
and then subsequently introduced into another sexually incompatible
food plant.
VI. Rulemaking Record and Procedures
Any person who has registered or submitted an application for
registration of a pesticide, under FIFRA as amended, which contains any
plant-pesticide that falls within a category proposed for exemption may
request within 30 days after publication of this proposed rule in the
Federal Register that this rulemaking proposal be referred to an
Advisory Committee in accordance with section 408(e) of the FFDCA.
EPA has established a record for this rulemaking. Interested
persons are invited to submit written comments on the proposed
regulation. Comments must bear a notation indicating the document
control number, (OPP-300368). All written comments filed in response to
this petition will be available in the Public Response and Program
Resources Branch, at the location listed under the ADDRESSES unit from
8 a.m. to 4 p.m., Monday through Friday, except legal holidays.
VII. Regulatory Assessment Requirements
The Office of Management and Budget has exempted this proposed rule
from the requirement of review pursuant to Executive Order 12866.
Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator
has determined that regulations establishing new tolerances or raising
tolerance levels or establishing exemptions from tolerance requirements
do not have a significant economic impact on a substantial number of
small entities. A certification statement to this effect was published
in the Federal Register of May 4, 1981 (46 FR 24950).
This proposed rule is not subject to the Paperwork Reduction Act
because it does not contain any collection of information requirements.
VIII. References
(1) International Food Biotechnology Council, 1990. Biotechnologies
and food: Assuring the safety of foods produced by genetic
modification. In: Regulatory Toxicology and Pharmacology. Vol. 12.
Academic Press, New York.
(2) 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.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Plants, Plant-
pesticides.
Dated: November 15, 1994.
Carol M. Browner,
Administrator.
Therefore, it is proposed that 40 CFR part 180 be amended as
follows:
PART 180--[AMENDED]
1. The authority citation for part 180 would continue to read as
follows:
Authority: 21 US.C. 346a and 371.
2. By adding Sec. 180.1137 to read as follows:
Sec. 180.1137 Plant-pesticides; exemptions from the requirement of a
tolerance.
(a) Residues of pesticidal substances produced in living plants as
plant-pesticides are exempt from the requirement of a tolerance 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.
(b) Residues of pesticidal substances produced in living plants as
plant-pesticides are exempt from the requirement of a tolerance when
the genetic material that encodes for a pesticidal substance or leads
to the production of a pesticidal substance is derived from plants that
are not sexually compatible with the recipient plant if:
(1) The genetic material that encodes for a pesticidal substance or
leads to the production of a pesticidal substance is derived from food
plants.
(2) The pesticidal substances would not result in significantly
different dietary exposures.
(c) For the purposes of this section, the following definitions
apply:
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.
Food plant means a plant which, either in part or in toto, is used
as food by humans.
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.
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.
Major crops for human dietary consumption means wheat, corn,
soybeans, potatoes, oranges, tomatoes, grapes, apples, peanuts, rice,
beans, and any other crop that the Agency has determined is a major
crop for human dietary consumption.
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.
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.
Result in significantly different dietary exposure means:
(1) The pesticidal substance is produced in inedible portions of
the source food plant, but, in the recipient plant, the pesticidal
substance is present in the plant's edible portion.
(2) The pesticidal substance is produced in the immature, but not
in the mature, edible portions of the source food plant, but, in the
recipient plant, the pesticidal substance is present in the mature,
edible portions.
(3) The pesticidal substance is from a source food plant normally
cooked or processed prior to consumption and is produced in a recipient
plant that is not normally cooked or processed prior to consumption.
(4) The pesticidal substance is derived from a source food plant
that is not a major crop for human dietary consumption and is
introduced into a recipient plant that is a major crop for human
dietary consumption.
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 and/or wide crosses between plants.
Source food plant 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.
[FR Doc. 94-28823 Filed 11-22-94; 8:45 am]
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