[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: 94-28825]
[[Page Unknown]]
[Federal Register: November 23, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300371; FRL-4755-5]
RIN 2070-AC02
Plant-Pesticides; Proposed Exemption From the Requirement of a
Tolerance Under the Federal Food, Drug, and Cosmetic Act for Nucleic
Acids Produced in Plants
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 for residues
of nucleic acids (i.e., deoxyribonucleic acid and ribonucleic acid)
produced in plants as part of a plant-pesticide active or inert
ingredient. Nucleic acids are ubiquitous in all forms of life, have
always been present in human and domestic animal food and are not known
to cause any adverse health effects when consumed as part of a food
plant. Thus, EPA believes that a tolerance for nucleic acids produced
in plants is not necessary to protect the public health.
DATES: Comments identified by the docket control number [OPP-300371]
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: 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 and Purpose of Proposed Regulation
Substances that are produced in plants to enable the plants to
resist pests or disease are pesticides under FIFRA 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.''
This proposed rule would exempt nucleic acids (i.e.,
deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)) from the
requirement for a tolerance when such nucleic acids are produced in
plants as part of a plant-pesticide active or inert ingredient. Nucleic
acids encoding for pesticidal substances and selectable markers are
considered to be part of the active and inert ingredients for plant-
pesticides. Under this proposed rule, an active ingredient, when
referring to plant-pesticides only, would be 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.'' An inert ingredient, when referring to
plant-pesticides only, would be ``any substance, such as a selectable
marker, other than the active ingredient(s), 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.''
Nucleic acids encoding for pesticidal substances and selectable
markers are considered to be part of the active and inert ingredients
for plant-pesticides 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. Including the genetic
material as part of these definitions also 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 permits the Agency to address plant-
pesticides 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).
DNA and RNA are common to all forms of life, including plants, and
the Agency knows of no instance where these nucleic acids have been
associated with any toxic effects related to the consumption of foods.
Thus, the Agency believes that a tolerance for nucleic acids produced
in plants as part of plant-pesticide active or inert ingredients is not
necessary to protect the public health. The Agency is therefore
proposing to exempt such nucleic acids from the requirement of a
tolerance. This proposed rule is one of several proposed exemptions
from the requirement of a tolerance for plant-pesticides published in
today's issue of the Federal Register. The other proposed exemptions
under FFDCA are: (1) A proposed exemption from the requirement of a
tolerance 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 (2) a proposed exemption from the requirement of a tolerance for
plant-pesticides that would 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'').
II. Statutory Authority
This exemption from the requirement of a tolerance is being
proposed under the authority of section 408 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 pesticide
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. Scientific Rationale
The Agency's proposal for exempting nucleic acids produced in
plants as part of a plant-pesticide active or inert ingredient from the
requirement of a tolerance is based on the ubiquity of nucleic acids
and their presence in human and domestic animal food without observed
adverse health effects.
Nucleic acids encode the information necessary to produce the
enzymes and structural proteins essential for cellular viability.
Nucleic acids are also the chemical basis for heritable traits. Once
new combinations of nucleic acids are stably integrated into a plant's
germ cells, these new combinations will be reproduced and be part of
the genetic complement of all that plant's progeny. Thus, if the
genetic information needed for production of a pesticidal substance is
stably introduced into the plant, that plant and its progeny will have
the potential to produce the pesticidal substance.
Chemically, the naturally occurring nucleic acids occur in two
types: deoxyribonucleic acid and ribonucleic acid. DNA is a polymer of
purine and pyrimidine base deoxyribonucleoside monophosphates. These
individual components are called nucleotides and are commonly referred
to by the different base names distinguishing them: adenine (A),
cytosine (C), guanine (G), and thymine (T). The other nucleic acid,
RNA, is a polymer of purine and pyrimidine base riboside
monophosphates. The nucleotides are referred to by their base names
also: adenine (A), cytosine (C), guanine (G), and uracil (U).
These chemicals are widespread in foods and have not, by
themselves, been associated with toxic or pathogenic effects on animals
or humans. None of these constituents of nucleic acids are known to be
acute toxicants by themselves but, like proteins and other normal
constituents of food, may cause indirect, adverse metabolic effects if
consumed exclusively at high doses over a long period of time in the
absence of a normal balanced diet. Nucleic acids never occur at these
high amounts in food plants and have not been associated with any toxic
effects related to the consumption of foods.
The Agency is aware that there are nucleic acid analogues (e.g.,
altered purine or pyrimidine bases) that may be considered ``nucleic
acids'' by their chemical composition. Certain analogues are being
developed as therapeutic agents for human diseases and nucleic acid
analogues could conceivably be developed as pesticides. The Agency is
not proposing to exempt nucleic acid analogues from the requirement for
a food tolerance in this regulation. The intent of this proposal is to
exempt only the naturally occurring, non-modified nucleic acids
(ribosides or deoxyribosides of A, T, G, C, and U) and polymers of such
substances commonly found in living cells that serve as the mechanism
of encoding traits associated with pesticidal substances produced by
plants.
One application of recombinant DNA technology in plants has been
the introduction of DNA sequences that code for the RNA complement
(anti-sense) of the messenger RNA (mRNA) for an essential enzyme or
component of an obligate parasite. This RNA complement or anti-sense
RNA binds the target mRNA and prevents it from binding to ribosomes,
effectively terminating synthesis of the essential enzyme. This
methodology is currently being developed for introducing pest-
resistance into plants. It should be noted that the Agency believes
that nucleic acids involved in this technology do not present a hazard
to the public health and would meet the requirements for this food
tolerance exemption.
The Agency has no evidence that nucleic acids by themselves present
any hazard to human or domestic animal health and therefore these
substances, when associated with a plant-pesticide as part of an active
or inert ingredient, do not require a food tolerance to protect the
public health.
IV. External Review
On July 13, 1993, a Subcommittee of EPA's Biotechnology Science
Advisory Committee (BSAC) was convened to address a series of questions
concerning EPA's regulatory approach under FFDCA. The BSAC Subcommittee
confirmed that nucleic acids (DNA and RNA), which are present in the
cells of every living organism, including plants, microorganisms and
animals, used for food, do not raise safety concerns as a component of
food. EPA agrees with the BSAC Subcommittee and proposes to exempt
nucleic acids produced in plants from the requirement of a tolerance
under FFDCA.
Based on the above information, the Agency finds that the exemption
from the requirement of a tolerance established by amending 40 CFR
180.xxxx would protect the public health. Therefore, it is proposed
that the tolerance exemption be established as set forth in the
proposed regulatory text of this document.
V. 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
of the ingredients listed herein, 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-300371). All written comments filed in response to
this proposal and the rest of the rulemaking record are available in
the Public Response and Program Resources Branch, at the address given
above from 8 a.m. to 4 p.m., Monday through Friday, except legal
holidays.
VI. Regulatory 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.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, 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 part 180 be amended as
follows:
PART 180--[AMENDED]
1. The authority citation for part 180 would continue to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. By adding Sec. 180.1138 to read as follows:
Sec. 180.1138 Nucleic acids produced in plants; exemption from the
requirement of a tolerance.
(a) Residues of nucleic acids produced in living plants as part of
a plant-pesticide active or inert ingredient, including both
deoxyribonucleic and ribonucleic acids, are exempt from the requirement
of a tolerance.
(b) For the purposes of this section, the following definitions
apply:
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.
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.
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.
Nucleic acids means ribosides or deoxyribosides of adenine,
thymine, guanine, cytosine, and uracil and the polymers of these
ribosides and deoxyribosides and does not apply to nucleic acid
analogues.
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.
[FR Doc. 94-28825 Filed 11-22-94; 8:45 am]
BILLING CODE 6560-50-F
