[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: 94-28824]


[[Page Unknown]]

[Federal Register: November 23, 1994]


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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[OPP-300367; FRL-4755-4]
RIN 2070-AC02

 

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

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 
residues of coat proteins from plant viruses when these coat proteins 
are produced as plant-pesticides in plants or plant parts used as raw 
agricultural commodities. Viral coat proteins are a specific class of 
pesticidal substances that can be produced in plants. These pesticidal 
substances, along with the genetic material necessary to produce them 
are designated ``plant-pesticides'' by EPA. EPA's proposal for 
exempting coat proteins from plant viruses from the requirement of a 
tolerance is based on virus-infected plants having always been part of 
the human and domestic animal food supply without detectable adverse 
health effects. Thus, EPA believes that a tolerance for viral coat 
proteins produced in plants is not necessary to protect the public 
health.

DATES: Comments identified by the docket control number [OPP-300367] 
must be received on or before January 23, 1995.

ADDRESSESS: 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 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.'' Under this proposal 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.'' Viral coat proteins produced in plants for viral coat protein 
mediated viral resistance are considered plant-pesticides because of 
their intended role in plant resistance to viral infection.
    EPA is proposing to exempt from the requirement of a tolerance coat 
proteins from plant viruses when these are produced in plants for the 
purpose of protecting plants against viral disease. Because of the 
characteristics of viral coat proteins, the Agency does not believe 
that a tolerance for these pesticidal substances is necessary to 
protect the public health.
    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 nucleic acids in plants (``Plant-pesticides; Proposed Exemption 
from the Requirement of a Tolerance Under the Federal Food, Drug, and 
Cosmetic Act for Nucleic Acids Produced in Plants,'' and (2) a proposed 
exemption from the requirement of a tolerance for plant-pesticides that 
will 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 (FFDCA) (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

A. Summary

    Coat proteins are those substances that viruses produce to 
encapsulate and protect their genetic material. When the genetic 
material encoding for the coat protein is introduced into a plant's 
genome, the plant is able to resist infections by the virus donating 
the genetic material for the coat protein (as well as strains closely 
related to the donor virus). This resistance is termed viral coat 
protein mediated resistance or vcp-mediated resistance.
    EPA's rationale for finding that a tolerance for viral coat 
proteins in foods is not necessary to protect the public health rests 
on the points discussed in this preamble. These points are: (1) Virus-
infected plants have always been a part of the human and domestic 
animal food supply since most crops are frequently infected with plant 
viruses and food from these crops have been and are being consumed 
without detectable adverse human health effects. (2) Plant viruses have 
never been shown to be infectious to humans or mammals. Plant viruses 
are not able to replicate in mammals or other vertebrates, limiting the 
possibility of human infection. In addition, this exemption applies 
only to the portion of the viral genome coding for the whole coat 
protein or a sub-component of the coat protein which will be expressed 
in the plant during viral coat protein mediated resistance. This 
portion by itself is incapable of forming infectious particles. Since 
whole, intact plant viruses are not known to cause deleterious human 
health effects, it is reasonable to assume that a subunit of these 
viruses likewise will not cause adverse human health effects.

B. Presence in Food Supply and Inability to Replicate in Vertebrates

    Entire infectious particles of the plant pathogenic virus, 
including the coat protein component, have been and are being consumed 
by humans with no observed adverse effects. Virus-infected food plants 
have always been a part of the human and domestic animal food supply 
(Refs. 1, 6, and 7). At the beginning of this century virtually every 
commercial cultivar of potatoes grown in the United States and Europe 
was infected with either one or some complex of potato viruses (Ref. 
1).
    All plants have viruses that can infect them. While some viruses 
may be limited to certain tissues (e.g., the vascular system) or organs 
(e.g., roots), most plant viruses are found throughout the various 
organs and tissues of plants. Viruses, including the coat protein 
component, are found in the fruit, leaves, and stems of most plants. 
The long history of inadvertent mammalian consumption of the entire 
plant virus particle in foods with no observed ill effects presents a 
strong argument to support the human and domestic animal safety of the 
entire virus in foods.
    Concentrations of the virus particles in infected plants vary 
widely according to the host plant, length of infection, and the 
reproductive life cycle of the virus itself. Current crop varieties 
bred for virus resistance are usually tolerant to virus infection 
rather than actually being resistant or immune to infection, i.e., they 
do not express gross disease symptoms even though these resistant 
varieties can contain concentrations of virus similar to susceptible 
varieties (Ref. 5). The levels of virus in virus-infected plants can be 
as high as 0.1 to 0.3 mg/gm tissue as seen with Tobacco Mosaic Virus 
(Ref. 5). The total amount of virus particles, including the coat 
protein component, in naturally infected plants can often be several 
orders of magnitude higher than the concentration expected for viral 
coat proteins expressed as plant-pesticides. Plants modified to be 
virus resistant through viral coat protein mediated resistance 
generally express coat proteins from plant viruses at concentrations 
two to three orders of magnitude lower than plants naturally infected 
by viruses (Ref. 6). Thus, consumers could be exposed to less coat 
protein through plants expressing coat proteins than through virus-
infected crops. However, the average amount of coat protein a consumer 
might ingest in food from a virus susceptible crop could, in some 
instances, be less than the average amount present in food from plants 
protected from virus infection through the production of viral coat 
proteins since food from the virus susceptible crop might be derived 
from both virus-free and virus-infected plants. In general, though, EPA 
anticipates that the amounts of viral coat protein consumed in the diet 
due to the production of viral coat proteins in vcp-mediated resistance 
will be similar to the amounts of viral coat proteins currently 
consumed.
    Plant pathogenic viruses have never been shown capable of infecting 
or replicating in vertebrates (Refs. 2, 3, 4, and 5). Intact, 
infectious, whole plant viruses, therefore, are not infectious to 
humans. Given that the complete virus is not infectious to vertebrates, 
it is reasonable to assume that a noninfectious subcomponent of the 
virus would not be hazardous to humans or animals. Purified 
preparations of plant viruses have routinely been handled by 
researchers without specialized protection of workers (researchers) 
against infection. These purified plant virus preparations are also 
frequently injected into laboratory animals for the production of 
specific antibodies without any adverse effects to the animals. No 
specific toxicological testing of purified plant virus preparations has 
been reported in the literature.

IV. External Review

    In developing its regulatory approach for plant-pesticides, EPA 
requested the advice of a Subpanel of the FIFRA Scientific Advisory 
Panel (SAP). On December 18, 1992, the SAP Subpanel was convened to 
review a draft policy statement for plant-pesticides and respond to a 
series of scientific questions posed by the Agency.
    One question that the Agency asked the SAP Subpanel was whether 
coat proteins from plant viruses might present a dietary risk. In 
answer to the question the Subpanel stated that ``[s]ince viruses are 
ubiquitous in the agricultural environment at levels higher than will 
be present in transgenic plants, and there has been a long history of 
`contamination' of the food supply by virus coat protein, there is [a] 
scientific rationale for exempting transgenic plants expressing virus 
coat protein from the requirement of a tolerance.'' EPA agrees with 
this position and is proposing an exemption from the requirement of a 
tolerance for coat proteins from plant viruses when produced in plants.
    Based on the information presented in this document, EPA finds that 
a tolerance for viral coat proteins produced in plants is not necessary 
to protect the public health. Thus, it is proposed that an exemption 
from the requirement of a tolerance be established by amending 40 CFR 
part 180 as set forth in the regulatory text of this document.

V. Rulemaking Record and Procedure

    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-300367). All written comments filed in response to 
this proposal and the rest of the rulemaking record will be 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.

VII. References

    (1) Beemster, A.B.R. and J.A. de Bokx. 1987. Survey of Properties 
and Symptoms of Potato Viruses, pp. 84-93 In: Viruses of Potatoes and 
Seed Potato Production; J.A. de Bokx and J.P.H. vanderWant. PuDOC, 
Wageningen, The Netherlands.
    (2) Brun, G. 1991. ``Rhabdoviridae''. Chap. 17, pp. 443-460; In: 
Atlas of Invertebrate Viruses eds. J.R. Adams and J.R. Bonami. CRC 
Press, Boca Raton, FL.
    (3) EPA Issue Paper. Issues associated with the regulation of viral 
coat proteins under FIFRA and FFDCA.
    (4) Gibbs, A. and B. Harrison. 1976. Plant Virology: The 
Principles, Chap. 1. J. Wiley Sons, New York.
    (5) Matthews, R.E.F. 1981. Plant Virology. Chaps. 12, 16, and 19. 
Second edition, Academic Press, New York.
    (6) Palukaitis, P. 1991. Virus-mediated genetic transfer in plants. 
In: Risk Assessment in Genetic Engineering. Edited by M.A. Levin and 
H.S. Strauss. McGraw-Hill, Inc., New York. pp. 140-161.
    (7) Provvidenti, R., R.W. Robinson, and H.M. Munger. 1984. 
Occurance of Zucchini Yellow Mosaic Virus in Curcubits from 
Connecticut, New York, Florida and California, Plant Disease 68:443-
446.

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. 180.1136 to read as follows:


Sec. 180.1136   Viral coat proteins used as plant-pesticides; exemption 
from the requirement of a tolerance.

    (a) Residues of coat proteins from plant viruses, or segments of 
the coat proteins, produced in living plants as plant-pesticides are 
exempt from the requirement of a tolerance.
    (b) For the purpose of this section, the following definitions 
apply:
    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.

[FR Doc. 94-28824 Filed 11-22-94; 8:45 am]
BILLING CODE 6560-50-F