Plant-Pesticides; Nucleic Acids; Supplemental Notice of Proposed Rulemaking

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300371A; FRL-5716-7]

RIN 2070-AC02

Plant-Pesticides; Nucleic Acids; Supplemental Notice of Proposed

Rulemaking

AGENCY: Environmental Protection Agency (EPA).

ACTION: Supplemental notice of proposed rulemaking.

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SUMMARY: This document announces the availability of information for

additional public comment regarding a proposed exemption from the

requirement of a tolerance under the Federal Food, Drug, and Cosmetic

Act (FFDCA) for residues of nucleic acids (i.e., deoxyribonucleic acid

and ribonucleic acid) produced in plants as part of a plant-pesticide.

Comments on this document may also affect EPA's final determination on

three proposed exemptions under the Federal Insecticide, Fungicide, and

Rodenticide Act (FIFRA). In 1994, EPA proposed to exempt from the

requirement of tolerance residues of nucleic acids produced in plants

as part of a plant-pesticide because such a tolerance would not be

necessary to protect the public health. Since publication of the

proposal, Congress enacted the Food Quality Protection Act (FQPA) which

amended FFDCA and FIFRA. EPA is issuing this document today to provide

the public with an opportunity to comment on EPA's analysis of how

certain FQPA amendments to FFDCA and FIFRA apply to the proposed

exemption from the requirement of a tolerance for residues of nucleic

acids produced in plants as part of a plant-pesticide. EPA believes

that it considered most of the substantive issues associated with the

FQPA amendments when it issued the proposal in 1994. EPA is, thus, in

this document, specifically seeking comment only on its evaluation of

the requirements imposed by FQPA that the Agency did not address in the

proposal.

DATES: Comments, identified by the docket control number ``OPP-

300371A,'' must be received on or before June 16, 1997.

ed most of the substantive issues associated with the

FQPA amendments when it issued the proposal in 1994. EPA is, thus, in

this document, specifically seeking comment only on its evaluation of

the requirements imposed by FQPA that the Agency did not address in the

proposal.

DATES: Comments, identified by the docket control number ``OPP-

300371A,'' must be received on or before June 16, 1997.

ADDRESSES: By mail, submit written comments to: Public Information and

Records Integrity Branch, Information Resources and Services Division

(7506C), Office of Pesticide Programs, Environmental Protection Agency,

401 M St., SW., Washington, DC 20460. In person deliver comments to:

Rm. 1132, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA

22202.

Comments and data may also be submitted electronically by following

the instructions under Unit VI. of this document. No Confidential

Business Information (CBI) should be submitted through e-mail.

FOR FURTHER INFORMATION CONTACT: Elizabeth Milewski, Office of Science,

Coordination and Policy, Office of Prevention, Pesticides and Toxic

Substances (7101), Environmental Protection Agency, 401 M St., SW.,

Washington, DC 20460, Telephone: (202) 260-6900, e-mail:

[email protected].

SUPPLEMENTARY INFORMATION:

I. Introduction

EPA issued in the November 23, 1994 Federal Register a package of

five separate Federal Register proposals (59 FR 60496, 60519, 60535,

60542 and 60545) (FRL-4755-2, FRL-4755-3, FRL-4758-8, FRL-4755-5, and

FRL-4755-4) which together described EPA's approach to substances

produced in plants that enable the plants to resist pests or disease.

EPA's package of proposals indicated that these substances are

pesticides under section 2 of FIFRA (7 U.S.C. 136(u)) if they are

``intended for preventing, destroying, repelling, or mitigating any

pest'' or if they are ``. .

5-3, FRL-4758-8, FRL-4755-5, and

FRL-4755-4) which together described EPA's approach to substances

produced in plants that enable the plants to resist pests or disease.

EPA's package of proposals indicated that these substances are

pesticides under section 2 of FIFRA (7 U.S.C. 136(u)) if they are

``intended for preventing, destroying, repelling, or mitigating any

pest'' or if they are ``. . . intended for use as a plant regulator,

defoliant, or desiccant'' regardless of whether the pesticidal

capabilities evolved in the plants or were introduced by breeding or

through the techniques of modern biotechnology. These substances, and

the genetic material necessary to produce them, were designated

``plant-pesticides'' by EPA in the November 23, 1994, Federal Register

notices. The notices defined a ``plant-pesticide'' as ``a pesticidal

substance that is produced in a living plant and the genetic material

necessary for the production of the pesticidal substance where the

pesticidal substance is intended for use in the living plant'' (59 FR

at 60534).

One of the five documents (59 FR 60542) proposed to exempt from the

requirement of a tolerance residues of nucleic acids (i.e.,

deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)) when such

nucleic acids are produced in plants as part of a plant-pesticide

(i.e., the genetic material necessary to produce the pesticidal

substance). This supplemental notice addresses the nucleic acids

portion of plant-pesticides produced in food plants. Because FQPA

modified FIFRA ( 7 U.S.C. 136 et seq.) by incorporating the FFDCA

safety standard into the FIFRA test for determining whether a pesticide

poses an unreasonable adverse effect, comments on this supplemental

notice may also affect EPA's final determination on proposed exemptions

under FIFRA for three categories of plant-pesticides (59 FR at 60535):

ticides produced in food plants. Because FQPA

modified FIFRA ( 7 U.S.C. 136 et seq.) by incorporating the FFDCA

safety standard into the FIFRA test for determining whether a pesticide

poses an unreasonable adverse effect, comments on this supplemental

notice may also affect EPA's final determination on proposed exemptions

under FIFRA for three categories of plant-pesticides (59 FR at 60535):

(1) Those that are derived from a plant that is sexually compatible

with the recipient plant, (2) those that act primarily by affecting the

plant, and (3) those that are coat proteins from plant viruses.

EPA is publishing this supplemental notice to ensure that the

public has had adequate opportunity to comment on certain new

considerations raised by the FQPA amendments to FFDCA as these

considerations relate to the proposed exemption from a tolerance for

residues of the nucleic acid portion of plant-pesticides produced in

food plants. In evaluating a pesticide chemical residue for exemption

from FFDCA tolerance requirements, EPA must now explicitly address

certain factors, and make a determination that there is a reasonable

certainty that aggregate exposure to the residue will cause no harm to

the public. The factors to be considered are iterated in Unit II. of

this supplemental notice. EPA's evaluation of these factors relative to

the proposed exemption (59 FR 60535) is contained in Unit IV. of this

supplemental notice. Consistent with FFDCA section 408(c)(2)(B), EPA

has reviewed the available scientific data and other relevant

information in support of this action. In today's supplemental notice,

EPA requests comment only on the new conclusions identified in Unit

V.C.

In light of FQPA, EPA is engaged in a process, including

consultation with registrants, states, and other interested

stakeholders, to make decisions on the

FFDCA section 408(c)(2)(B), EPA

has reviewed the available scientific data and other relevant

information in support of this action. In today's supplemental notice,

EPA requests comment only on the new conclusions identified in Unit

V.C.

In light of FQPA, EPA is engaged in a process, including

consultation with registrants, states, and other interested

stakeholders, to make decisions on the

new policies and procedures that will be appropriate as a result of

enactment of FQPA. In establishing this exemption from the requirement

of a tolerance for residues of nucleic acids produced in plants as part

of a plant-pesticide, EPA does not intend to set precedents for the

application of section 408 and the new safety standard to other

tolerances and exemptions. This exemption from the requirement of a

tolerance will not restrict EPA's options with regard to general

procedures and policies for implementation of the amended FFDCA section

408.

II. Statutory Authority

Under FFDCA, EPA regulates pesticide chemical residues by

establishing tolerances limiting the amounts of residues that may be

present in food, or by establishing exemptions from the requirement of

a tolerance for such residues. Pesticide chemical residues subject to

regulation under FFDCA are defined by reference to the definition of

pesticide under FIFRA. FFDCA section 201(q)(1) defines a ``pesticide

chemical residue'' to mean the residue in or on food of a pesticide

chemical or other added substance resulting primarily from the

metabolism or degradation of a pesticide chemical (21 U.S.C. 321

ce for such residues. Pesticide chemical residues subject to

regulation under FFDCA are defined by reference to the definition of

pesticide under FIFRA. FFDCA section 201(q)(1) defines a ``pesticide

chemical residue'' to mean the residue in or on food of a pesticide

chemical or other added substance resulting primarily from the

metabolism or degradation of a pesticide chemical (21 U.S.C. 321

(q)(2)). A ``pesticide chemical'' means ``any substance that is a

pesticide within the meaning of the Federal Insecticide, Fungicide, and

Rodenticide Act, including all active and inert ingredients of such

pesticide'' (21 U.S.C. 321(q)(1)).

FIFRA authorizes EPA to regulate the sale and distribution of

pesticides in the United States and to exempt a pesticide from the

requirements of FIFRA if it is not of a character requiring regulation

(7 U.S.C. 136a(a) and 136w(b)). FIFRA section 2(u) defines

``pesticide'' as: (1) ``any substance or mixture of substances intended

for preventing, destroying, repelling, or mitigating any pest, (2) any

substance or mixture of substances intended for use as a plant

regulator, defoliant, or desiccant, and (3) any nitrogen stabilizer''

(7 U.S.C. 136(u)).

FQPA amends both FFDCA and FIFRA. FQPA, which took effect on August

3, 1996, among other things, amends FIFRA such that a registration

cannot be issued for a pesticide to be used on or in food unless the

residue of the pesticide in food qualifies for a tolerance or exemption

from the requirement for a tolerance. FQPA modified FIFRA section 2(bb)

by incorporating the FFDCA section 408 safety standard into the test

for determining whether a pesticide poses an unreasonable adverse

effect (7 U.S.C. 136(bb))

that a registration

cannot be issued for a pesticide to be used on or in food unless the

residue of the pesticide in food qualifies for a tolerance or exemption

from the requirement for a tolerance. FQPA modified FIFRA section 2(bb)

by incorporating the FFDCA section 408 safety standard into the test

for determining whether a pesticide poses an unreasonable adverse

effect (7 U.S.C. 136(bb)). FIFRA section 2(bb) defines the term

``unreasonable adverse effects on the environment'' to mean (1) any

unreasonable risk to man or the environment, taking into account the

economic, social, and environmental costs and benefits of the use of

any pesticide, or (2) a human dietary risk from residues that result

from a use of a pesticide in or on any food inconsistent with the

standard under section 408 of the FFDCA. Thus, a pesticide used in or

on food that does not meet the FFDCA section 408 safety standard also

would pose an unreasonable adverse effect under FIFRA and would not

qualify for an exemption from the requirements of FIFRA under FIFRA

section 25(b)(2).

FQPA amends FFDCA section 408(c)(2)(A)(i) to allow EPA to establish

an exemption from the requirement of a tolerance for a ``pesticide

chemical residue'' only if EPA determines that the exemption is

``safe'' (21 U.S.C. 346a(c)(2)(A)(i)). Section 408(c)(2)(A)(ii) defines

``safe'' to mean that ``there is a reasonable certainty that no harm

will result from aggregate exposure to the pesticide chemical residue,

including all anticipated dietary exposures and all other exposures for

which there is reliable information'' (21 U.S.C. 346a(c)(2)(A)(ii)).

This includes exposure through drinking water, but does not include

occupational exposure. In establishing an exemption from the

requirement of a tolerance, FFDCA section 408(c), like the statute

prior to FQPA, does not require EPA to consider benefits that might be

associated with use of the pesticide chemical

xposures for

which there is reliable information'' (21 U.S.C. 346a(c)(2)(A)(ii)).

This includes exposure through drinking water, but does not include

occupational exposure. In establishing an exemption from the

requirement of a tolerance, FFDCA section 408(c), like the statute

prior to FQPA, does not require EPA to consider benefits that might be

associated with use of the pesticide chemical.

FFDCA section 408 requires EPA to give special consideration to

exposure of infants and children to the pesticide chemical residue in

establishing an exemption and to ``ensure that there is a reasonable

certainty that no harm will result to infants and children from

aggregate exposure to the pesticide chemical residue'' (21 U.S.C.

346a(b)(2)(C)(ii)(I)) and (c)(2)(B). Section 408(b)(2)(D) specifies

other, general factors EPA is to consider in establishing an exemption.

Section 408(c)(3)(B) prohibits an exemption unless there is either a

practical method for detecting and measuring levels of pesticide

chemical residue in or on food or there is no need for such a method

(21 U.S.C. 346a(c)(3)(B)).

Specifically, EPA must consider the following in deciding whether

to grant an exemption:

1. The validity, completeness, and reliability of the available

data from studies of the pesticide chemical and chemical pesticide

residue.

2. Nature of any toxic effect shown to be caused by the pesticide

chemical or residues in studies.

3. Available information concerning the relationship of the results

of such studies to human risk.

4. Available information concerning the dietary consumption

patterns of consumers (and major identifiable subgroups of consumers).

5. Available information concerning the cumulative effects of such

residues and other substances that have a common mechanism of toxicity.

6. Available information concerning the aggregate exposure levels

of consumers to the pesticide chemical residue and to other related

substances, including dietary exposure and non-occupational exposures.

7

(and major identifiable subgroups of consumers).

5. Available information concerning the cumulative effects of such

residues and other substances that have a common mechanism of toxicity.

6. Available information concerning the aggregate exposure levels

of consumers to the pesticide chemical residue and to other related

substances, including dietary exposure and non-occupational exposures.

7. Available information concerning the variability of the

sensitivities of major identifiable subgroups of consumers.

8. Such information as the Administrator may require on whether the

pesticide chemical may have an effect in humans that is similar to an

effect produced by a naturally-occurring estrogen or other endocrine

effects.

9. Safety factors which in the opinion of experts qualified by

scientific training and experience to evaluate the safety of food

additives are generally recognized as appropriate for the use of animal

experimentation data (21 U.S.C. 346a(b)(2)(D)).

Additionally, with respect to exposure of infants and children,

consistent with section 408(b)(2)(C), EPA must assess the risk of the

pesticide based on available information concerning:

1. Consumption patterns that are likely to result in

disproportionately high consumption of food with pesticide residues.

2. Special susceptibility of infants and children to such residues.

3. Cumulative effects of residues with other substances that have a

common mechanism of toxicity (21 U.S.C. 346a(b)(2)(C) and (c)(2)(B)).

III. Summary of Proposed Regulation

The proposal (59 FR 60542) described how EPA would view: (1)

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), (2) nucleic

acid analogues (e.g., altered purine or pyrimidine bases) that may be

considered ``nucleic acids'' by their chemical composition, and (3) DNA

sequences that code for the RNA complement (anti-sense) of the

messenger RNA (mRNA) for an essential enzyme or other component of an

obligate parasite.

escribed how EPA would view: (1)

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), (2) nucleic

acid analogues (e.g., altered purine or pyrimidine bases) that may be

considered ``nucleic acids'' by their chemical composition, and (3) DNA

sequences that code for the RNA complement (anti-sense) of the

messenger RNA (mRNA) for an essential enzyme or other component of an

obligate parasite.

In the November 23, 1994 Federal Register, EPA proposed to exempt

nucleic acids (i.e., deoxyribonucleic acid (DNA) and ribonucleic acid

(RNA)) from the requirement of a tolerance when such nucleic acids are

produced in plants as part of a plant-pesticide (59 FR 60542). In the

proposal, EPA stated that the proposed exemption from the requirement

of a tolerance for the nucleic acids portion of plant-pesticides

produced in food plants is based on the ubiquity of nucleic acids in

all forms of life, their presence in human and domestic animal food and

the consequent large scale exposure of the human population with no

evidence nucleic acids have caused any adverse health effects when

consumed as part of a food plant. The Agency knows of no instance where

nucleic acids naturally occurring in plants have been associated with

any toxic effects related to the consumption of foods.

In the 1994 proposal, EPA recognized that nucleic acid analogues

(e.g., altered purine or pyrimidine bases) 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 proposed

exemption does not extend to such nucleic acid analogues. The 1994

proposal only proposed to exempt 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 encode

the information necessary to make the pesticidal substances produced by

plants

developed as pesticides. The proposed

exemption does not extend to such nucleic acid analogues. The 1994

proposal only proposed to exempt 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 encode

the information necessary to make the pesticidal substances produced by

plants.

The 1994 proposal also discussed how EPA proposed to view the

introduction into plants 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. One mechanism by which

this RNA complement or anti-sense RNA is believed to work is to bind to

the target mRNA and prevent it from binding to ribosomes, effectively

terminating synthesis of the essential enzyme or other enzymes for

making other essential cellular components necessary to survival of the

parasite. This methodology is currently being developed for introducing

pest-resistance into plants. As was noted in the proposed exemption,

the Agency believes that the introduction and expression in plants of

nucleic acids in this anti-sense technology do not present a hazard to

the public health and such nucleic acids would qualify for this food

tolerance exemption.

IV. Risk Assessment and Safety Determinations

A. Risk Assessment in Proposal

This unit reviews the analysis that EPA used to support its 1994

proposal (59 FR 60535) to exempt nucleic acids (DNA and RNA, including

DNA and RNA used in anti-sense technology) produced in plants as part

of a plant-pesticide from the requirement of a tolerance under FFDCA.

EPA also relied upon the analysis in the 1994 FFDCA proposal to

evaluate human dietary risks in support of its proposal (59 FR 60519)

to exempt three categories of plant-pesticides (59 FR at 60535) from

most FIFRA requirements

encoded in the nucleic acid is determined by the sequence

in which the heterocyclic bases are attached to the sugar-phosphate

backbone. Thus, the ``genetic material necessary for the production of

the pesticidal substance'' are the nucleic acids encoding the

information necessary for a plant cell to make the pesticidal

substance.

Nucleic acids are also the chemical basis for heritable traits.

When nucleic acids encoding the genetic information needed for the

production of a pesticidal substance is stably integrated into the

plant, that plant and its progeny will have the potential to produce

the pesticidal substance.

Nucleic acids are widespread in foods and have not, by themselves,

been associated with toxic or pathogenic effects on animals or humans.

None of the constituents of nucleic acids are known to be acute

toxicants, 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

consumption of foods.

In the proposal, the Agency made clear that it is not proposing to

exempt nucleic acid analogues from the requirement of a food tolerance.

These analogues are not naturally occurring and those used as

therapeutic agents frequently have significant toxicity associated with

their use. The intent of EPA's 1994 proposal was to exempt only the

naturally occurring, non-modified nucleic acids, and polymers of such

substances, commonly found in living cells that serve as the mechanisms

of encoding traits associated with pesticidal substances produced by

plants

aturally occurring and those used as

therapeutic agents frequently have significant toxicity associated with

their use. The intent of EPA's 1994 proposal was to exempt only the

naturally occurring, non-modified nucleic acids, and polymers of such

substances, commonly found in living cells that serve as the mechanisms

of encoding traits associated with pesticidal substances produced by

plants.

EPA proposed to extend this exemption (59 FR 60542) from the

requirement of a tolerance to the mRNA used in anti-sense technology

based on the consideration that these mRNAs are analogous to naturally

occurring, non-modified nucleic acid polymers commonly found in living

cells. The rationale applied in the proposal to other naturally

occurring, non-modified nucleic acid polymers applies equally to these

mRNAs; the ubiquity of nucleic acids and their presence in human and

domestic animal food and no observed adverse health effects associated

with consumption of foods containing nucleic acids.

B. Risk Assessment in Light of Amendment to FFDCA

After EPA issued its proposed exemption from the requirement of a

tolerance for nucleic acids produced in plants as part of a plant-

pesticide (59 FR 60542), Congress enacted FQPA and amended certain

FFDCA provisions governing pesticide chemical residues and FIFRA

provisions governing pesticides (See Unit II. of this supplemental

notice). Congress revised the specific wording of the section 408

standard for exemptions and provided more specific guidance regarding

some of the factors that EPA should consider in establishing such

exemptions (see

), Congress enacted FQPA and amended certain

FFDCA provisions governing pesticide chemical residues and FIFRA

provisions governing pesticides (See Unit II. of this supplemental

notice). Congress revised the specific wording of the section 408

standard for exemptions and provided more specific guidance regarding

some of the factors that EPA should consider in establishing such

exemptions (see

Unit II. of this supplemental notice). When EPA proposed the exemption

for residues of nucleic acids produced in plants as part of a plant-

pesticide (59 FR 60535), it considered most of the safety factors

spelled out in FQPA even though the Agency may not have explicitly

discussed all those factors using the terminology specified in the FQPA

amendments. This supplemental notice describes how the Agency took

account of most of the FQPA factors in issuing its 1994 proposal to

exempt from the requirement of a tolerance nucleic acids produced in

plants as part of a plant-pesticide, and indicates which factors were

considered in that proposal. The information the Agency relied on in

considering these factors is part of the public record which was

available to the public when EPA issued the proposed exemption from the

requirement of a food tolerance. The supplemental notice also

identifies the factors that were not considered in the proposal.

Because FQPA amended FIFRA by incorporating the section 408 safety

standard, commenters should be aware that comments on this supplemental

notice may also affect EPA's final determination on the proposed

exemptions (59 FR at 60535) under FIFRA for three categories of plant-

pesticides: (1) Those that are derived from plants sexually compatible

with the recipient plant, (2) those that act primarily by affecting the

plant, and (3) those that are coat proteins from plant viruses.

1. Validity, completeness, and reliability of available data

may also affect EPA's final determination on the proposed

exemptions (59 FR at 60535) under FIFRA for three categories of plant-

pesticides: (1) Those that are derived from plants sexually compatible

with the recipient plant, (2) those that act primarily by affecting the

plant, and (3) those that are coat proteins from plant viruses.

1. Validity, completeness, and reliability of available data. EPA

considered in 1994 the validity, completeness, and reliability of the

available data with regard to nucleic acids produced in plants as part

of a plant-pesticide in the proposals (59 FR 60519 and 60542) and has

described the evaluation in Unit IV.A. of this supplemental notice.

2. Nature of toxic effect. EPA in 1994 considered the nature of the

toxic effects caused by nucleic acids produced in plants as part of a

plant-pesticide in the proposals (59 FR 60519 and 60542) and has

described its evaluation in Unit IV.A. of this supplemental notice.

3. Relationship of studies to humans. EPA in 1994 considered the

available information concerning the relationship of available data on

toxicity of nucleic acids produced in plants as part of a plant-

pesticide to humans when it issued the proposal to exempt these

substances from the requirement of a tolerance. EPA has summarized its

evaluation in Unit IV.A. of this supplemental notice. The nature of the

toxic effect of nucleic acids was assessed in light of the known

presence of nucleic acids in all consumed foods (Ref. 1) and the

history of human consumption of food derived from crop plants, and from

products such as meat and milk from animals that consume forage and

other crops (e.g., corn and other grains) that contain residues of

nucleic acids. EPA determined in the proposal that nucleic acids

produced in plants as part of a plant-pesticide do not have a toxic

effect and have no adverse effects to humans

) and the

history of human consumption of food derived from crop plants, and from

products such as meat and milk from animals that consume forage and

other crops (e.g., corn and other grains) that contain residues of

nucleic acids. EPA determined in the proposal that nucleic acids

produced in plants as part of a plant-pesticide do not have a toxic

effect and have no adverse effects to humans. Because knowledge of

human consumption of food containing nucleic acids was available and

adequately addressed the issues of hazard and exposure, the Agency did

not use, for the proposed exemption (59 FR 60542), data generated in

the laboratory through animal testing.

4. Dietary consumption patterns. EPA considered in the 1994

proposal the available information on the varying dietary consumption

patterns of major identifiable consumer subgroups as it pertains to

nucleic acids in food from plants. As described in the 1994 proposal,

nucleic acids are ubiquitous in nature and in the food supply. Nucleic

acids that make up the genetic material in plant-pesticides will not

alter this baseline consumption pattern of nucleic acids. The Agency's

evaluation is summarized in Unit IV.A. of this supplemental notice.

5. Available information concerning cumulative effects of the

pesticide chemical residue and other substances that have a common

mechanism of toxicity. EPA in 1994 examined the available information

on the cumulative effect of nucleic acids in food from plants and other

substances that have a common mechanism of toxicity. EPA summarizes

this information and its analysis in Unit IV.A. of this supplemental

notice.

Nucleic acids are widespread in food and have not been associated

with direct toxic or pathogenic effects to animals or humans. Because

nucleic acids in foods have no human toxicity, no cumulative effects

can be identified for nucleic acids produced in plants as part of a

plant-pesticide

of toxicity. EPA summarizes

this information and its analysis in Unit IV.A. of this supplemental

notice.

Nucleic acids are widespread in food and have not been associated

with direct toxic or pathogenic effects to animals or humans. Because

nucleic acids in foods have no human toxicity, no cumulative effects

can be identified for nucleic acids produced in plants as part of a

plant-pesticide. FQPA also directs the Agency to examine whether there

are other substances that have a common mechanism of toxicity with

nucleic acids produced in plants as part of a plant-pesticide. Based on

available information which indicates that nucleic acids in food have

no human toxicity, EPA is not aware of any other substances that might

have a common mechanism of human toxicity with nucleic acids produced

in plants as part of a plant-pesticide.

EPA is not aware of any substances outside of the food supply that

may have a common mechanism of toxicity with nucleic acids produced in

plants as part of a plant-pesticide since nucleic acids in plant food

are not toxic. EPA has identified nucleic acid analogues as substances

having some level of toxicity; however, their mechanism of toxicity is

not cumulative with that of naturally occurring nucleic acids (DNA and

RNA).

EPA considered the safety of foods containing residues of nucleic

acids when it issued the proposal and is not requesting additional

comment on that topic. Comments are only requested on EPA's conclusion

that there are no substances outside of the food supply that may have a

cumulative toxic effect with residues of nucleic acids produced in

plants as part of a plant-pesticide.

6. Aggregate exposures of consumers including non-occupational

exposures. EPA considered the available information on the aggregate

exposure level of consumers to nucleic acids produced in plants as part

of a plant-pesticide in the 1994 FFDCA and FIFRA proposals (59 FR 60519

and 60542)

a

cumulative toxic effect with residues of nucleic acids produced in

plants as part of a plant-pesticide.

6. Aggregate exposures of consumers including non-occupational

exposures. EPA considered the available information on the aggregate

exposure level of consumers to nucleic acids produced in plants as part

of a plant-pesticide in the 1994 FFDCA and FIFRA proposals (59 FR 60519

and 60542). This included a consideration of exposures from dietary

sources (59 FR 60542) as well as from other non-occupational sources

(59 FR 60519). As indicated in EPA's policy statement, ``plant-

pesticides are likely to present a limited exposure of the pesticidal

substance to humans. In most cases, the predominant, if not the only,

exposure route will be dietary. Significant respiratory and dermal

exposures will be unlikely'' (59 FR at 60513). As explained in the

FFDCA and FIFRA proposals and EPA's policy statement (59 FR 60496) and

associated dockets, plant-pesticides present negligible exposure of

pesticidal substances to humans outside of the dietary route because

the substances are in the plant tissue and thus are found either within

the plant or in close proximity to the plant. This is particularly true

for the nucleic acid portion of plant-pesticides. EPA considered

dietary exposure to nucleic acids produced in plants as part of a

plant-pesticide in the proposed FFDCA exemption (59 FR 60542) and

summarized its evaluation in Unit IV.A. of this supplemental notice.

Despite EPA's belief that, because of the nature of nucleic acids

produced in plants as part of a plant-pesticide, there is little

likelihood of exposure other than through the dietary route, EPA in

this supplemental notice sets forth in greater detail its

considerations concerning other exposure routes. With regard to the

dermal route of exposure, nucleic acids produced in plants as part of a

plant-pesticide may in some cases be present in sap or other exudates

from the plant or the food and thus may

e, there is little

likelihood of exposure other than through the dietary route, EPA in

this supplemental notice sets forth in greater detail its

considerations concerning other exposure routes. With regard to the

dermal route of exposure, nucleic acids produced in plants as part of a

plant-pesticide may in some cases be present in sap or other exudates

from the plant or the food and thus may

present some limited opportunity for dermal exposure to persons coming

physically into contact with the plant or raw agricultural food from

the plant. Individuals preparing meals are those most likely to

experience dermal contact with the substances on a non-occupational

basis. However, on a per person basis, the potential amounts involved

in these exposures are negligible in comparison to potential exposure

through the dietary route. Moreover, substances that occur naturally in

food, including the nucleic acids produced in plants as part of plant-

pesticides, are unlikely to cross the barrier provided by the skin.

This is particularly true for nucleic acids produced in plants as part

of a plant-pesticide as they are large polymers.

With regard to exposure through inhalation, nucleic acids produced

in plants as part of a plant-pesticide may in some cases be present in

pollen and some individuals (those near enough to farms, nurseries, or

other plant-growing areas to be exposed to wind-blown pollen) may be

exposed, through inhalation, to the pollen. On a per person basis, the

potential amounts of pollen involved in these exposures are negligible

in comparison to potential exposure through the dietary route.

Moreover, it is unlikely that exposure to the pollen is equivalent to

exposure to nucleic acids produced in plants as part of a plant-

pesticide. In pollen, nucleic acids will likely be integrated into the

tissue of the pollen grain and not bound to the surface of the pollen

grain

pollen involved in these exposures are negligible

in comparison to potential exposure through the dietary route.

Moreover, it is unlikely that exposure to the pollen is equivalent to

exposure to nucleic acids produced in plants as part of a plant-

pesticide. In pollen, nucleic acids will likely be integrated into the

tissue of the pollen grain and not bound to the surface of the pollen

grain. Pollen grains and the substances that occur naturally in pollen

are unlikely to cross the barrier provided by the mucous membrane of

the respiratory tract and thus are not additive to dietary exposure.

EPA also evaluated potential non-occupational exposures in drinking

water. As noted in the preceding paragraphs, the substances in plants

or parts of plants, including nucleic acids produced in plants as part

of a plant-pesticide, are produced inside the plant itself. Nucleic

acids are an integral part of the living tissue of the plant. When the

plant dies or a part is removed from the plant, microorganisms

colonizing the tissue immediately begin to digest it, using the

components of the tissue (including nucleic acids produced in plants as

part of plant-pesticides) as building blocks for making their own

tissues or for fueling their own metabolisms. Nucleic acids produced in

plants as part of a plant-pesticide are subject to the same processes

of degradation and decay that all organic matter undergoes. This

turnover of biochemical materials in nature through a process of

degradation occurs fairly rapidly. Indeed, nucleic acids are highly

unstable outside of the cellular environment and are very quickly

broken down. Therefore, nucleic acids produced in plants as part of a

plant-pesticide do not persist in the environment or bioaccumulate.

There is no indication that naturally occurring nucleic acids produced

in plants as part of plant-pesticides, are resistant to this

degradation

irly rapidly. Indeed, nucleic acids are highly

unstable outside of the cellular environment and are very quickly

broken down. Therefore, nucleic acids produced in plants as part of a

plant-pesticide do not persist in the environment or bioaccumulate.

There is no indication that naturally occurring nucleic acids produced

in plants as part of plant-pesticides, are resistant to this

degradation. Because of the very rapid turnover of these substances,

even if they reach surface waters (e.g., through plant parts falling

into bodies of water), they are unlikely to present anything other than

a very negligible exposure in drinking water drawn either from surface

or ground water sources. Therefore, the potential for non-dietary

exposure (i.e., non-food oral, dermal and inhalation) in non-

occupational settings is extremely limited and EPA expects such

exposure to be negligible.

With regard to exposure to ``other related substances,'' EPA is not

aware of any other substances either in food or outside the food supply

that may be related, via a common mechanism of toxicity, to nucleic

acids produced in plants as part of a plant-pesticide since nucleic

acids are not toxic. With regard to non-occupational exposure through

routes other than dietary exposure, since nucleic acids have no

mechanism of toxicity, EPA is not aware of substances in food or

outside the food supply that may be related via a common mechanism of

toxicity to the nucleic acids that are produced in plants as a plant-

pesticide. No evidence indicates that adverse effects due to aggregate

exposure of nucleic acids with these substances through the dietary,

non-food oral, dermal and inhalation routes occurs.

EPA considered exposure to nucleic acids produced in plants as a

part of a plant-pesticide when it issued the proposal and it is not

requesting additional comment on this topic

uced in plants as a plant-

pesticide. No evidence indicates that adverse effects due to aggregate

exposure of nucleic acids with these substances through the dietary,

non-food oral, dermal and inhalation routes occurs.

EPA considered exposure to nucleic acids produced in plants as a

part of a plant-pesticide when it issued the proposal and it is not

requesting additional comment on this topic. Comments are requested

only on EPA's conclusion that there are no additional substances

outside the food supply that are related, via a common mechanism of

toxicity, to residues of nucleic acids produced in plants as part of a

plant-pesticide for which EPA must consider exposure in aggregate with

nucleic acids.

7. Sensitivities of subgroups. In 1994, EPA considered available

information on the sensitivities of subgroups as it pertains to the

nucleic acids produced in plants as part of a plant-pesticide in the

proposal (59 FR 60542). The Agency's evaluation is summarized in Unit

IV.A. of this supplemental notice.

8. Naturally occurring estrogen or other endocrine effects. FFDCA

now directs EPA, in establishing an exemption from the requirement of a

tolerance, to consider ``such information as the Administrator may

require on whether the pesticide chemical may have an effect in humans

that is similar to an effect of a naturally occurring estrogen or other

endocrine effect'' (21 U.S.C. 346(a)(q)). Congress allowed EPA 2 years

to establish a screening program to determine whether certain pesticide

chemicals may have estrogenic effects and an additional year to

implement the program (21 U.S.C. 408(p)). As part of the screening and

implementation process, EPA is determining what information might be

required and how it will address estrogenic effects from pesticide

residues in general.

Based on available information concerning their structure and mode

of action, EPA does not expect nucleic acids produced in plants as part

of a plant-pesticide to cause estrogen or other endocrine effects

)). As part of the screening and

implementation process, EPA is determining what information might be

required and how it will address estrogenic effects from pesticide

residues in general.

Based on available information concerning their structure and mode

of action, EPA does not expect nucleic acids produced in plants as part

of a plant-pesticide to cause estrogen or other endocrine effects.

There is some information on estrogenic effects by exposure to

pesticides but the data are limited and do not pertain to nucleic

acids. If EPA becomes aware of a potential for estrogenic or endocrine

effect from exposure to nucleic acids produced in plants as part of a

plant-pesticide, EPA will reexamine this tolerance exemption in light

of that information.

9. Safety factors. In the 1994 proposal, EPA did not rely on the

available animal data in reaching its determination that a tolerance is

not necessary to protect the public from nucleic acids produced in

plants as part of a plant-pesticide (59 FR 60542). As discussed in Unit

IV.A. of this supplemental notice, EPA relied on the long history of

safe human consumption of food containing nucleic acids produced in

plants as part of a plant-pesticide and in food derived from animals

that consume forage and other crops (e.g., corn and other grains). EPA

continues to believe that long-term evidence of human consumption, not

animal experimentation data, is the appropriate information base for

the proposed exemption (59 FR 60542). Because EPA did not rely on

animal experimentation data, the Agency did not consider which safety

factors would be appropriate to use in assessing risk to humans based

on data generated through experiments on animals.

10. Infants and children.--a. Dietary consumption patterns. In the

1994 proposal (59 FR 60542), EPA considered available information on

the dietary consumption pattern of infants and children as it pertains

to nucleic acids produced in plants as part of a plant-

hich safety

factors would be appropriate to use in assessing risk to humans based

on data generated through experiments on animals.

10. Infants and children.--a. Dietary consumption patterns. In the

1994 proposal (59 FR 60542), EPA considered available information on

the dietary consumption pattern of infants and children as it pertains

to nucleic acids produced in plants as part of a plant-

pesticide and has summarized the evaluation in Unit IV.A. of this

supplemental notice. The range of foods consumed by infants and

children is in general more limited than the range of foods consumed by

adults. Most newborns rely on milk products for nutrition, although

some infants are fed soy-based products. Infants begin as early as 4-

months of age to consume specific types of solid foods. Subsequent to 4

months of age, apart from processing to facilitate swallowing, the

diets of infants are based on foods consumed by the general adult

population albeit in different proportions. As infants and children

mature, more and more of the foods normally consumed by adults become

part of their diets and the relative proportions of the different types

of food consumed changes to more closely resemble an adult diet. All

foods consumed by infants and children contain nucleic acids.

b. Special susceptibility. In the 1994 proposal (59 FR 60542), EPA

considered available information on the potential for susceptibility of

infants and children, including pre- and post-natal toxicity, as these

factors pertain to the nucleic acids produced in plants as part of a

plant-pesticide. There is no scientific evidence that nucleic acids as

a component of food would have a different effect on children than they

would on the adult population. EPA summarizes its analysis of the

effect of consumption in food of nucleic acids on human health in Unit

IV.A. of this supplemental notice.

c. Cumulative effects of residues with other substances with a

common mechanism of toxicity

ide. There is no scientific evidence that nucleic acids as

a component of food would have a different effect on children than they

would on the adult population. EPA summarizes its analysis of the

effect of consumption in food of nucleic acids on human health in Unit

IV.A. of this supplemental notice.

c. Cumulative effects of residues with other substances with a

common mechanism of toxicity. In the 1994 proposal (59 FR 60542), EPA

examined the available information on the cumulative effect of residues

of nucleic acids produced in plants as part of a plant-pesticide as

well as other substances in food that may have a common mechanism of

toxicity. The Agency's consideration in the proposal of the effects of

the residues of nucleic acids produced in plants as part of a plant-

pesticide on the general population also included consideration of

effects for infants and children. See Unit IV.B.5. of this supplemental

notice for a discussion of cumulative effects of nucleic acids and

other substances that have a common mechanism of toxicity.

Because EPA already considered the safety of food containing

residues of nucleic acids produced in plants as part of a plant-

pesticide and other constituents of food when it issued the proposal

(59 FR 60542), the Agency is not requesting additional comment on that

topic. Comments are requested only on EPA's conclusion that there are

no substances outside of the food supply with a common mechanism of

toxicity to the residues of nucleic acids produced in plants as part of

a plant-pesticide.

d. Margin of safety

lant-

pesticide and other constituents of food when it issued the proposal

(59 FR 60542), the Agency is not requesting additional comment on that

topic. Comments are requested only on EPA's conclusion that there are

no substances outside of the food supply with a common mechanism of

toxicity to the residues of nucleic acids produced in plants as part of

a plant-pesticide.

d. Margin of safety. In determining whether the residues of nucleic

acids produced in plants as part of a plant-pesticide are safe, FFDCA

section 408(b)(2)(C) directs EPA to apply a tenfold margin of safety

for the residues and other sources of exposure to infants and children

to account for potential pre- and post-natal toxicity and completeness

of data on threshold effects with respect to exposure and toxicity to

infants and children, unless a different margin will be safe. In

proposing the exemption, EPA based its assessment of exposure and

toxicity upon reliable information (Ref. 1) including the long history

of safe human consumption of food containing residues of nucleic acids

produced in plants as part of a plant-pesticide and other substances in

food, and the unique nature of plant-pesticides. EPA did not rely on

animal data. EPA relied on observations concerning whole food

consumption by humans and did not rely on single entity testing,

wherein substances are isolated from a plant source, and fed to animals

at high concentrations (Ref. 1). EPA relied on the vast base of the

human experience with actual food consumption rather than limited

testing situations. EPA thus, did not utilize animal or other studies

that would yield data that could be subjected to an additional margin

of safety. (See Units IV.A. and IV.B.3. of this supplemental notice).

As a result, the FQPA amendments to FFDCA do not affect EPA's analysis.

C. Safety Determinations in Light of FFDCA Amendment

experience with actual food consumption rather than limited

testing situations. EPA thus, did not utilize animal or other studies

that would yield data that could be subjected to an additional margin

of safety. (See Units IV.A. and IV.B.3. of this supplemental notice).

As a result, the FQPA amendments to FFDCA do not affect EPA's analysis.

C. Safety Determinations in Light of FFDCA Amendment

Based on the information discussed in the 1994 proposals (59 FR

60496 through 60547), the discussion in Unit IV.A. and the analysis in

Unit IV.B. of this supplemental notice, EPA concludes that there is a

reasonable certainty that no harm will result to the U.S. population in

general, and U.S. infants and children, from aggregate exposure to

residues of nucleic acids produced in plants as part of a plant-

pesticide, including all anticipated dietary exposures and all other

exposures for which there is reliable information. Under the proposed

exemption from the requirement for a tolerance (59 FR 60542), EPA would

exempt residues of nucleic acids produced in plants as part of a plant-

pesticide. Extensive use and experience show the safety of foods

containing these substances. No evidence, in the many years of human

experience with the growing and consumption of food from plants

containing residues of nucleic acids produced in plants as part of a

plant-pesticide, indicates that adverse effects due to aggregate

exposure through the dietary, non-food oral, dermal and inhalation

routes occur.

The conclusion that residues of nucleic acids produced in plants as

part of a plant-pesticide should be exempt from tolerance requirements

under the FFDCA section 408 safety standard also lends support to EPA's

proposed FIFRA exemptions (59 FR 60519) with respect to human dietary

risks

effects due to aggregate

exposure through the dietary, non-food oral, dermal and inhalation

routes occur.

The conclusion that residues of nucleic acids produced in plants as

part of a plant-pesticide should be exempt from tolerance requirements

under the FFDCA section 408 safety standard also lends support to EPA's

proposed FIFRA exemptions (59 FR 60519) with respect to human dietary

risks. These exemptions are: (1) Plant-pesticides that are derived from

a plant that is sexually compatible with the recipient plant, (2)

plant-pesticides that act primarily by affecting the plant, and (3)

plant-pesticides that are coat proteins from plant viruses (59 FR at

60535). In the FIFRA proposal, EPA utilized two criteria to determine

whether plant-pesticides should be exempt; (1) whether they posed a low

probability of risk, and (2) whether they caused unreasonable adverse

effects on the environment. Based upon the determination that residues

of the three categories of pesticidal substances subject to the

proposed exemptions (59 FR 60535) and the nucleic acid component of a

plant-pesticide (59 FR 60542) meet the FFDCA section 408 safety test,

EPA concludes plant-pesticides in the three proposed categories of

exemption would pose only a low probability of human dietary risk and

also would not pose an unreasonable adverse effect with respect to such

risks.

D. Other Considerations.

When the Agency proposed to establish an exemption from the

requirement of a tolerance for nucleic acids produced in plants as part

of a plant-pesticide (59 FR 60542), EPA did not propose any numerical

limitation on the amount of nucleic acids that could be present in food

containing these residues. EPA consulted in 1994 with the Department of

Health and Human Services (DHHS) in developing the proposed exemption

and this supplemental notice and will consult with the Secretary of HHS

prior to issuing the final rule

s part

of a plant-pesticide (59 FR 60542), EPA did not propose any numerical

limitation on the amount of nucleic acids that could be present in food

containing these residues. EPA consulted in 1994 with the Department of

Health and Human Services (DHHS) in developing the proposed exemption

and this supplemental notice and will consult with the Secretary of HHS

prior to issuing the final rule. Because the 1994 proposal was an

exemption from the requirement of a tolerance, the Agency has concluded

that an analytical method for detecting and measuring the levels of the

residues of nucleic acids in or on food is not required.

V. Comments

A. Confidential Business Information

Information submitted as a comment concerning this supplemental

notice may be claimed confidential by marking any part or all of that

information as ``Confidential Business Information'' (CBI). CBI should

not be submitted through e-mail. Information marked as CBI 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.

B. 30-Day Comment Period

EPA is allowing a 30-day comment period because it has determined

that such a period will provide the public with an adequate opportunity

to respond to the additional issues raised in this supplemental notice.

FFDCA and FIFRA do not specify a comment period for this type of

notice. EPA has decided that a 30-day comment period is reasonable

because this supplemental notice raises very few new issues that were

not already available for public comment. As discussed in Unit IV

od will provide the public with an adequate opportunity

to respond to the additional issues raised in this supplemental notice.

FFDCA and FIFRA do not specify a comment period for this type of

notice. EPA has decided that a 30-day comment period is reasonable

because this supplemental notice raises very few new issues that were

not already available for public comment. As discussed in Unit IV. of

this supplemental notice, EPA effectively considered most of the

factors required by the FQPA amendments of FFDCA and FIFRA relevant to

the proposed exemptions when it issued the proposed package of notices

describing EPA's approach in 1994 (59 FR 60496, 60519, 60535, 60542 and

60545). At that time, the public had an opportunity to review both the

Agency's rationale for the proposals and the underlying support

documents during a 90-day public comment period. Only a limited number

of new issues have been raised by the FQPA amendments to FFDCA and

FIFRA and the Agency continues to rely upon the information already in

the docket for the 1994 proposals and thus 30 days should provide

adequate time for public comment. In addition, EPA believes that it is

in the interest of the public to publish the final exemption from the

requirement of a tolerance in a timely manner.

C. Request for Comments

Interested persons are invited to submit written comments on the

new issues raised in this supplemental notice specifically on:

(1) EPA's conclusion that there are no substances outside of the

food supply that may have a cumulative toxic effect with residues of

nucleic acids produced in plants as part of a plant-pesticide.

quirement of a tolerance in a timely manner.

C. Request for Comments

Interested persons are invited to submit written comments on the

new issues raised in this supplemental notice specifically on:

(1) EPA's conclusion that there are no substances outside of the

food supply that may have a cumulative toxic effect with residues of

nucleic acids produced in plants as part of a plant-pesticide.

(2) EPA's conclusion that there are no additional substances

outside the food supply that are related, via a common mechanism of

toxicity, to residues of nucleic acids produced in plants as part of a

plant-pesticide for which EPA must consider exposure in aggregate with

nucleic acids.

Commenters who possess information on nucleic acids causing

estrogenic effects are requested to send such information to EPA.

In this supplemental notice, EPA describes in greater detail the

rationale supporting the statement made in the 1994 Federal Register

(59 FR at 60513) that ``plant-pesticides are likely to present a

limited exposure of pesticidal substances to humans. In most cases, the

predominant, if not the only route of exposure will be dietary.

Significant respiratory and dermal exposures will be unlikely.'' No

comments were received on this statement during the official comment

period. Commenters may comment on this more detailed rationale.

In this supplemental notice, EPA also describes in greater detail

how the rationale presented in the 1994 Federal Register (59 FR at

60538) concerning the safety for human consumption of food containing

nucleic acids produced in plants as part of a plant-pesticide applies

to infants and children. No comments were received on this statement

during the official comment period. Commenters may comment on this more

detailed rationale specifically addressing infants and children as part

of the larger human population.

VI. Public Docket

oncerning the safety for human consumption of food containing

nucleic acids produced in plants as part of a plant-pesticide applies

to infants and children. No comments were received on this statement

during the official comment period. Commenters may comment on this more

detailed rationale specifically addressing infants and children as part

of the larger human population.

VI. Public Docket

The official record for this rulemaking, as well as the public

version, has been established for this rulemaking under docket control

number number ``OPP-300371A'' (including comments and data submitted

electronically as described below). A public version of this record,

including printed, paper versions of electronic comments, which does

not include any information claimed as CBI, is available for inspection

from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal

holidays. The official rulemaking record is located at the address in

``ADDRESSES'' at the beginning of this document.

Electronic comments can be sent directly to EPA at:

[email protected]

Electronic comments must be submitted as an ASCII file avoiding the

use of special characters and any form of encryption. Comment and data

will also be accepted on disks in WordPerfect 5.1 file format or ASCII

file format. All comments and data in electronic form must be

identified by the docket number ``OPP-300371A.'' Electronic comments on

this supplemental notice may be filed online at many Federal Depository

Libraries.

VII. References

file avoiding the

use of special characters and any form of encryption. Comment and data

will also be accepted on disks in WordPerfect 5.1 file format or ASCII

file format. All comments and data in electronic form must be

identified by the docket number ``OPP-300371A.'' Electronic comments on

this supplemental notice may be filed online at many Federal Depository

Libraries.

VII. 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.

VIII. Regulatory Assessment Requirements

This supplemental notice merely seeks additional comments on the

proposed rules with regard to the potential impact that the new

statutory amendments imposed by the August 3, 1996 Food Quality

Protection Act (FQPA) might have on the provisions as proposed. As

such, this notice does not contain any new proposed requirements that

would require additional consideration by the Office of Management and

Budget (OMB) under Executive Order 12866, entitled Regulatory Planning

and Review (58 FR 51735, October 4, 1993) or the Paperwork Reduction

Act (PRA), 44 U.S.C. 3501 et seq. It does not require any other action

under Executive Order 12875, entitled Enhancing the Intergovernmental

Partnership (58 FR 58093, October 28, 1993), Executive Order 12898,

entitled Federal Actions to Address Environmental Justice in Minority

Populations and Low-Income Populations (59 FR 7629, February 16, 1994),

or the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.). The

Agency's activities related to these regulatory assessment requirements

are discussed in the proposed rules.

EPA did not consider Title II of the Unfunded Mandates Reform Act

of 1995 (UMRA) (Pub. L. 104-4) at the proposal stage because the

proposed rules were issued prior to its enactment

ons (59 FR 7629, February 16, 1994),

or the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.). The

Agency's activities related to these regulatory assessment requirements

are discussed in the proposed rules.

EPA did not consider Title II of the Unfunded Mandates Reform Act

of 1995 (UMRA) (Pub. L. 104-4) at the proposal stage because the

proposed rules were issued prior to its enactment. Although this

supplemental notice is not subject to UMRA because it neither proposes

or finalizes any regulatory requirements, the applicability of the UMRA

requirements will be addressed in the final rules.

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: May 7, 1997.

Lynn R. Goldman,

Assistant Administrator for Prevention, Pesticides and Toxic

Substances.

[FR Doc. 97-12786 Filed 5-15-97; 8:45 am]

BILLING CODE 6560-50-F