[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