Bacillus Thuringiensis Modified Cry3A Protein and the Genetic Material Necessary for Its Production in Corn; Exemption from the Requirement of a Tolerance, 64128-64132 [E6-18223]
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Federal Register / Vol. 71, No. 211 / Wednesday, November 1, 2006 / Rules and Regulations
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 174
[EPA–HQ–OPP–2006–0784; FRL–8096–4]
Bacillus Thuringiensis Modified Cry3A
Protein and the Genetic Material
Necessary for Its Production in Corn;
Exemption from the Requirement of a
Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
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AGENCY:
I. General Information
SUMMARY: This regulation establishes a
permanent exemption from the
requirement of a tolerance for residues
of the Bacillus thuringiensis modified
Cry3A protein (mCry3A) and the genetic
material necessary for its production in
corn on field corn, sweet corn, and
popcorn when applied/used as a plantincorporated protectant. Syngenta
Seeds, Inc. submitted a petition to EPA
under the Federal Food, Drug, and
Cosmetic Act (FFDCA), as amended by
the Food Quality Protection Act of 1996
(FQPA), requesting an exemption from
the requirement of a tolerance. This
regulation eliminates the need to
establish a maximum permissible level
for residues of Bacillus thuringiensis
modified Cry3A protein (mCry3A) and
the genetic material necessary for its
production in corn.
DATES: This regulation is effective
November 1, 2006. Objections and
requests for hearings must be received
on or before January 2, 2007, and must
be filed in accordance with the
instructions provided in 40 CFR part
178 (see also Unit I.C. of the
SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a
docket for this action under docket
identification (ID) number EPA–HQ–
OPP–2006–0784. All documents in the
docket are listed in the index for the
docket. Although listed in the index,
some information is not publicly
available, e.g., Confidential Business
Information (CBI) or other information
whose disclosure is restricted by statute.
Certain other material, such as
copyrighted material, is not placed on
the Internet and will be publicly
available only in hard copy form.
Publicly available docket materials are
available in the electronic docket at
https://www.regulations.gov, or, if only
available in hard copy, at the OPP
Regulatory Public Docket in Rm. S-4400,
One Potomac Yard (South Building),
2777 S. Crystal Drive, Arlington, VA.
The Docket Facility is open from 8:30
a.m. to 4 p.m., Monday through Friday,
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excluding legal holidays. The Docket
telephone number is (703) 305–5805.
FOR FURTHER INFORMATION CONTACT:
Mike Mendelsohn, Biopesticides and
Pollution Prevention Division (7511P),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 308–8715; e-mail address:
mendelsohn.mike@epa.gov.
SUPPLEMENTARY INFORMATION:
A. Does this Action Apply to Me?
You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
This listing is not intended to be
exhaustive, but rather provides a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies
of this Document?
In addition to accessing an electronic
copy of this Federal Register document
through the electronic docket at https://
www.regulations.gov, you may access
this ‘‘Federal Register’’ document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://www.epa.gov/fedrgstr. You may
also access a frequently updated
electronic version of 40 CFR part 180
through the Government Printing
Office’s pilot e-CFR site at https://
www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing
Request?
Under section 408(g) of the FFDCA, as
amended by the FQPA, any person may
file an objection to any aspect of this
regulation and may also request a
hearing on those objections. The EPA
procedural regulations which govern the
submission of objections and requests
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for hearings appear in 40 CFR part 178.
You must file your objection or request
a hearing on this regulation in
accordance with the instructions
provided in 40 CFR part 178. To ensure
proper receipt by EPA, you must
identify docket ID number EPA–HQ–
OPP–2006–0784 in the subject line on
the first page of your submission. All
requests must be in writing, and must be
mailed or delivered to the Hearing Clerk
on or before January 2, 2007.
In addition to filing an objection or
hearing request with the Hearing Clerk
as described in 40 CFR part 178, please
submit a copy of the filing that does not
contain any CBI for inclusion in the
public docket that is described in
ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2
may be disclosed publicly by EPA
without prior notice. Submit your
copies, identified by docket ID number
EPA–HQ–OPP–2006–0784, by one of
the following methods.
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the on-line
instructions for submitting comments.
• Mail: Office of Pesticide Programs
(OPP) Regulatory Public Docket (7502P),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001.
• Delivery: OPP Regulatory Public
Docket (7502P), Environmental
Protection Agency, Rm. S-4400, One
Potomac Yard (South Building), 2777 S.
Crystal Drive, Arlington, VA. Deliveries
are only accepted during the Docket’s
normal hours of operation (8:30 a.m. to
4 p.m., Monday through Friday,
excluding legal holidays). Special
arrangements should be made for
deliveries of boxed information. The
Docket telephone number is (703) 305–
5805.
II. Background and Statutory Findings
In the Federal Register of October 27,
2004 (69 FR 62688) (FRL–7370–1), EPA
issued a notice pursuant to section
408(d)(3) of the FFDCA, 21 U.S.C.
346a(d)(3), announcing the filing of a
pesticide tolerance petition (PP 4F6838)
by Syngenta Seeds, Inc., P.O. Box
12257, 3054 Cornwallis Road, Research
Triangle Park, NC 27709–2257. The
petition requested that 40 CFR part 174
be amended by establishing a
permanent exemption from the
requirement of a tolerance for residues
of modified Cry3A protein (mCry3A)
and the genetic material necessary for
its production in corn. This notice
included a summary of the petition
prepared by the petitioner Syngenta
Seeds, Inc. One comment was received
in response to the notice of filing from
the National Corn Growers Association.
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They supported the petition and
requested EPA to quickly issue the final
rule.
On March 14-15, 2006, EPA held a
FIFRA Scientific Advisory Panel (SAP)
meeting, at https://www.epa.gov/scipoly/
sap/meetings/2006/index.htm#march to
address the scientific issues that arose
during the risk assessment of mCry3A.
EPA asked the SAP to comment on the
equivalence of the mCry3A proteins
from corn event MIR604 and from
recombinant E. coli - specifically the
presence of two forms in the bacterialproduced mCry3A protein and the
differences in bioactivity in the WCRM
bioassay. The majority of the Panel
concluded that the two forms of the
mCry3A are of relatively comparable
biological activity for the purposes of
the human health assessments based on
the amino acid sequence identity, lack
of glycosylation, and general stability.
EPA also asked the SAP to comment
on EPA’s conclusions regarding the lack
of mammalian toxicity and allergenicity
of the mCry3A protein-specifically the
impact of the less potent mCry3A form
on the results of the acute oral toxicity
tests and the usefulness of in vitro
digestibility studies and amino acid
sequence homology analysis as part of
the risk assessment. Overall, the Panel
was more concerned with the quality of
data, i.e. inadequately described
methods and poor reproduction of data
images. The Panel specifically noted
that the amino acid sequence analysis to
known toxins and allergens were
missing the following data:
Specification of which version of NCBI
database was utilized; descriptions of
parameters utilized; and dates accessed
for the BLAST search. EPA recognizes
that these are important parameters to
include in a description of an amino
acid analysis and is requiring
submission of additional information by
Syngenta Seeds, Inc. in order to confirm
the method used. However, EPA
maintains that the conclusions of the
amino acid sequence analysis are still
valid for the purpose of the risk
assessment. EPA reached this decision
based on the following: (1) Lack of
mammalian toxicity of mCry3A protein
as shown by the acute oral mouse study;
(2) mCry3A protein is rapidly digested
in SGF; (3) mCry3A protein originates
from a non-allergenic source; (4) lack of
sequence identity of mCry3A protein
with eight contiguous amino acids or
more than 35% identity over 80 amino
acids with known toxins or allergens;
and (5) mCry3A protein is not
glycosylated when expressed in corn.
Section 408(c)(2)(A)(i) of the FFDCA
allows EPA to establish an exemption
from the requirement for a tolerance (the
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legal limit for a pesticide chemical
residue in or on a food) only if EPA
determines that the exemption is ‘‘safe.’’
Section 408(c)(2)(A)(ii) of the FFDCA
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.’’ This includes
exposure through drinking water and in
residential settings, but does not include
occupational exposure. Pursuant to
section 408(c)(2)(B), in establishing or
maintaining in effect an exemption from
the requirement of a tolerance, EPA
must take into account the factors set
forth in section 408(b)(2)(C), which
require EPA to give special
consideration to exposure of infants and
children to the pesticide chemical
residue in establishing a tolerance 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. . . .’’ Additionally, section
408(b)(2)(D) of the FFDCA requires that
the Agency consider ‘‘available
information concerning the cumulative
effects of a particular pesticide’s
residues ’’ and ‘‘other substances that
have a common mechanism of toxicity.’’
EPA performs a number of analyses to
determine the risks from aggregate
exposure to pesticide residues. First,
EPA determines the toxicity of
pesticides. Second, EPA examines
exposure to the pesticide through food,
drinking water, and through other
exposures that occur as a result of
pesticide use in residential settings.
III. Toxicological Profile
Consistent with section 408(b)(2)(D)
of the FFDCA, EPA has reviewed the
available scientific data and other
relevant information in support of this
action and considered its validity,
completeness, and reliability and the
relationship of this information to
human risk. EPA has also considered
available information concerning the
variability of the sensitivities of major
identifiable subgroups of consumers,
including infants and children.
Data have been submitted
demonstrating the lack of mammalian
toxicity at high levels of exposure to the
mCry3A protein alone. These data
demonstrate the safety of the products at
levels well above maximum possible
exposure levels that are reasonably
anticipated in the crops. This is similar
to the Agency position regarding
toxicity and the requirement of residue
data for the microbial Bacillus
thuringiensis products from which this
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plant-incorporated protectant was
derived (See 40 CFR 158.740(b)(2)(i)).
For microbial products, further toxicity
testing and residue data are triggered by
significant acute effects in studies such
as the mouse oral toxicity study, to
verify the observed effects and clarify
the source of these effects (Tiers II and
III).
An acute oral toxicity study was
submitted for the mCry3A protein. The
acute oral toxicity data submitted
support the prediction that the mCry3A
protein would be non-toxic to humans.
Male and female mice (5 of each) were
dosed with 2,377 milligrams/kilograms
bodyweight (mg/kg bwt) of mCry3A
protein. With the exception of one
female in the test group that was
euthanized on day 2 (due to adverse
clinical signs consistent with a dosing
injury), all other mice survived the
study, gained weight, had no test
material-related clinical signs, and had
no test material-related findings at
necropsy.
When proteins are toxic, they are
known to act via acute mechanisms and
at very low dose levels (Sjoblad, Roy D.,
et al. ‘‘Toxicological Considerations for
Protein Components of Biological
Pesticide Products,’’ Regulatory
Toxicology and Pharmacology 15, 3–9
(1992)). Therefore, since no effects were
shown to be caused by the plantincorporated protectants, even at
relatively high dose levels, the mCry3A
protein is not considered toxic. Further,
amino acid sequence comparisons
showed no similarity between the
mCry3A protein and known toxic
proteins available in public protein data
bases. According to the Codex
Alimintarius guidelines, the assessment
of potential toxicity also includes
stability to heat (FAO/WHO Standards
Programme, 2001). Further data
demonstrate that mCry3A is inactivated
against Western corn rootworm, when
heated to 95 °C for 30 minutes.
Since mCry3A is a protein, allergenic
sensitivities were considered. Current
scientific knowledge suggests that
common food allergens tend to be
resistant to degradation by acid, and
proteases; may be glycosylated; and
present at high concentrations in the
food. Data have been submitted that
demonstrate that the mCry3A protein is
rapidly degraded by gastric fluid in
vitro. In a solution of simulated gastric
fluid 1 milligrams/milliliter (mg/mL)
mCry3A test protein mixed with
simulated gastric fluid (pH 1.2,
containing 2 mg/mL NaCl, 14 µL 6 N
HCl, and 2.7 mg/mL pepsin) resulting in
10 pepsin activity units/microgram (µg)
protein (complies with year 2000 U.S.
Pharmacopoeia recommendations),
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complete degradation of detectable
mCry3A protein occurred within 2
minutes. A comparison of amino acid
sequences of known allergens
uncovered no evidence of any homology
with mCry3A, even at the level of eight
contiguous amino acids residues.
Further, data demonstrate that mCry3A
is not glycosylated, and is present in
low levels in corn tissue. Therefore, the
potential for the mCry3A protein to be
a food allergen is minimal. As noted
above, toxic proteins typically act as
acute toxins with low dose levels.
Therefore, since no effects were shown
to be caused by the plant-incorporated
protectant, even at relatively high dose
levels, the mCry3A protein is not
considered toxic.
IV. Aggregate Exposures
In examining aggregate exposure,
section 408 of the FFDCA directs EPA
to consider available information
concerning exposures from the pesticide
residue in food and all other nonoccupational exposures, including
drinking water from ground water or
surface water and exposure through
pesticide use in gardens, lawns, or
buildings (residential and other indoor
uses).
The Agency has considered available
information on the aggregate exposure
levels of consumers (and major
identifiable subgroups of consumers) to
the pesticide chemical residue and to
other related substances. These
considerations include dietary exposure
under the tolerance exemption and all
other tolerances or exemptions in effect
for the plant-incorporated protectant
chemical residue, and exposure from
non-occupational sources. Exposure via
the skin or inhalation is not likely since
the plant-incorporated protectant is
contained within plant cells, which
essentially eliminates these exposure
routes or reduces these exposure routes
to negligible. Exposure via residential or
lawn use to infants and children is also
not expected because the use sites for
the mCry3A protein are all agricultural
for control of insects. Oral exposure, at
very low levels, may occur from
ingestion of processed corn products
and, potentially, drinking water.
However, oral toxicity testing done at a
dose in excess of 2 grams/kilogram (gm/
kg) showed no adverse effects.
Furthermore, the expression of the
modified Cry3A protein in corn kernals
has been shown to be in the parts per
million range, which makes the
expected dietary exposure several
orders of magnitude lower than the
amounts of mCry3A protein shown to
have no toxicity. Therefore, even if
negligible aggregate exposure should
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occur, the Agency concludes that such
exposure would present reasonable
certainty of no harm due to the lack of
mammalian toxicity and the rapid
digestibility demonstrated for the
mCry3A protein.
V. Cumulative Effects
Pursuant to FFDCA section
408(b)(2)(D)(v), EPA has considered
available information on the cumulative
effects of such residues and other
substances that have a common
mechanism of toxicity. These
considerations included the cumulative
effects on infants and children of such
residues and other substances with a
common mechanism of toxicity.
Because there is no indication of
mammalian toxicity, resulting from the
plant-incorporated protectant, we
conclude that there are no cumulative
effects for the mCry3A protein.
VI. Determination of Safety for U.S.
Population, Infants and Children
A. Toxicity and Allergenicity
Conclusions
The data submitted and cited
regarding potential health effects for the
mCry3A protein include the
characterization of the expressed
mCry3A protein in corn, as well as the
acute oral toxicity, and in vitro
digestibility of the proteins. The results
of these studies were determined
applicable to evaluate human risk, and
the validity, completeness, and
reliability of the available data from the
studies were considered.
Adequate information was submitted
to show that the mCry3A protein test
material derived from microbial cultures
was biochemically and functionally
similar to the protein produced by the
plant-incorporated protectant
ingredients in corn. Production of
microbially produced protein was
chosen in order to obtain sufficient
material for testing.
The acute oral toxicity data submitted
supports the prediction that the mCry3A
protein would be non-toxic to humans.
As mentioned above, when proteins are
toxic, they are known to act via acute
mechanisms and at very low dose levels
(Sjoblad, Roy D., et al. ‘‘Toxicological
Considerations for Protein Components
of Biological Pesticide Products,’’
Regulatory Toxicology and
Pharmacology 15, 3–9 (1992)). Since no
effects were shown to be caused by
mCry3A protein, even at relatively high
dose levels (2,377 mg/kg bwt), the
mCry3A protein is not considered toxic.
This is similar to the Agency position
regarding toxicity and the requirement
of residue data for the microbial
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Bacillus thuringiensis products from
which this plant-incorporated
protectant was derived. (See 40 CFR
158.740(b)(2)(i). Moreover, mCry3A
showed no sequence similarity to any
known toxin and was inactivated by
heat against Western corn rootworm. No
further toxicity testing and residue data
were required because for microbial
products, further toxicity testing and
residue data requirements are triggered
by significant acute effects in studies
such as the mouse oral toxicity study to
verify the observed effects and clarify
the source of these effects (Tiers II and
III).
Modified Cry3A protein residue
chemistry data were not required for a
human health effects assessment of the
subject plant-incorporated protectant
ingredients because of the lack of
mammalian toxicity. However, data
submitted demonstrated low levels of
mCry3A in corn tissues with less than
2 µg mCry3A protein/gram dry weight
in kernals and less than 30 µg mCry3A
protein/gram dry weight of whole corn
plant.
Since modified Cry3A is a protein, its
potential allergenicity is also considered
as part of the toxicity assessment. Data
considered as part of the allergenicity
assessment include that the modified
Cry3A protein came from Bacillus
thuringiensis which is not a known
allergenic source, showed no sequence
similarity to known allergens, was
readily degraded by pepsin, and was not
glycosylated when expressed in the
plant. Therefore, there is a reasonable
certainty that modified Cry3A protein
will not be an allergen.
Neither available information
concerning the dietary consumption
patterns of consumers (and major
identifiable subgroups of consumers
including infants and children) nor
safety factors that are generally
recognized as appropriate for the use of
animal experimentation data were
evaluated. The lack of mammalian
toxicity at high levels of exposure to the
mCry3A protein, as well as the minimal
potential to be a food allergen
demonstrate the safety of the product at
levels well above possible maximum
exposure levels anticipated in the crop.
The genetic material necessary for the
production of the plant-incorporated
protectant active ingredients are the
nucleic acids (DNA, RNA) which
comprise genetic material encoding
these proteins and their regulatory
regions. The genetic material (DNA,
RNA), necessary for the production of
mCry3A protein has been exempted
under the blanket exemption for all
nucleic acids (40 CFR 174.475).
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B. Infants and Children Risk
Conclusions
FFDCA section 408(b)(2)(C) provides
that EPA shall assess the available
information about consumption patterns
among infants and children, special
susceptibility of infants and children to
pesticide chemical residues and the
cumulative effects on infants and
children of the residues and other
substances with a common mechanism
of toxicity.
In addition, FFDCA section
408(b)(2)(C) also provides that EPA shall
apply an additional tenfold margin of
safety, also referred to as margins of
exposure (MOEs), for infants and
children in the case of threshold effects
to account for prenatal and postnatal
toxicity and the completeness of the
data base unless EPA determines that a
different MOE will be safe for infants
and children.
In this instance, based on all the
available information, the Agency
concludes that there is a finding of no
toxicity for the mCry3A protein and the
genetic material necessary for their
production. Thus, there are no threshold
effects of concern to infants and
children when the mCry3A protein is
used as a plant-incorporated protectant.
Accordingly, the Agency concludes that
the additional MOE is not necessary to
protect infants and children, and that
not adding any additional MOE will be
safe for infants and children.
C. Overall Safety Conclusion
There is a reasonable certainty that no
harm will result from aggregate
exposure to the U.S. population,
including infants and children, to the
mCry3A protein and the genetic
material necessary for its production.
This includes all anticipated dietary
exposures and all other exposures for
which there is reliable information.
The Agency has arrived at this
conclusion because, as discussed above,
no toxicity to mammals has been
observed, nor any indication of
allergenicity potential for the plantincorporated protectant.
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VII. Other Considerations
A. Endocrine Disruptors
The pesticidal active ingredient is a
protein, derived from sources that are
not known to exert an influence on the
endocrine system. Therefore, the
Agency is not requiring information on
the endocrine effects of the plantincorporated protectant at this time.
B. Analytical Method(s)
A method for extraction and ELISA
analysis of mCry3A protein in corn has
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been submitted and found acceptable by
the Agency.
C. Codex Maximum Residue Level
No Codex maximum residue levels
exist for the plant-incorporated
protectant Bacillus thuringiensis
mCry3A protein and the genetic
material necessary for its production in
corn.
VIII. Statutory and Executive Order
Reviews
This final rule establishes an
exemption from the requirement of a
tolerance under section 408(d) of the
FFDCA in response to a petition
submitted to the Agency. The Office of
Management and Budget (OMB) has
exempted these types of actions from
review under Executive Order 12866,
entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993).
Because this rule has been exempted
from review under Executive Order
12866 due to its lack of significance,
this rule is not subject to Executive
Order 13211, Actions Concerning
Regulations That Significantly Affect
Energy Supply, Distribution, or Use (66
FR 28355, May 22, 2001). This final rule
does not contain any information
collections subject to OMB approval
under the Paperwork Reduction Act
(PRA), 44 U.S.C. 3501 et seq., or impose
any enforceable duty or contain any
unfunded mandate as described under
Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public
Law 104–4). Nor does it require any
special considerations under Executive
Order 12898, entitled Federal Actions to
Address Environmental Justice in
Minority Populations and Low-Income
Populations (59 FR 7629, February 16,
1994); or OMB review or any Agency
action under Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
This action does not involve any
technical standards that would require
Agency consideration of voluntary
consensus standards pursuant to section
12(d) of the National Technology
Transfer and Advancement Act of 1995
(NTTAA), Public Law 104–113, section
12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are
established on the basis of a petition
under section 408(d) of the FFDCA,
such as the exemption from the
requirement of a tolerance in this final
rule, do not require the issuance of a
proposed rule, the requirements of the
Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.) do not apply. In
addition, the Agency has determined
that this action will not have a
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64131
substantial direct effect on States, on the
relationship between the national
government and the States, or on the
distribution of power and
responsibilities among the various
levels of government, as specified in
Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999). Executive Order 13132 requires
EPA to develop an accountable process
to ensure ‘‘meaningful and timely input
by State and local officials in the
development of regulatory policies that
have federalism implications.’’ ‘‘Policies
that have federalism implications’’ is
defined in the Executive order to
include regulations that have
‘‘substantial direct effects on the States,
on the relationship between the national
government and the States, or on the
distribution of power and
responsibilities among the various
levels of government.’’ This final rule
directly regulates growers, food
processors, food handlers and food
retailers, not States. This action does not
alter the relationships or distribution of
power and responsibilities established
by Congress in the preemption
provisions of section 408(n)(4) of the
FFDCA. For these same reasons, the
Agency has determined that this rule
does not have any ‘‘tribal implications’’
as described in Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 6, 2000). Executive
Order 13175, requires EPA to develop
an accountable process to ensure
‘‘meaningful and timely input by tribal
officials in the development of
regulatory policies that have tribal
implications.’’ ‘‘Policies that have tribal
implications’’ is defined in the
Executive order to include regulations
that have ‘‘substantial direct effects on
one or more Indian tribes, on the
relationship between the Federal
Government and the Indian tribes, or on
the distribution of power and
responsibilities between the Federal
Government and Indian tribes.’’ This
rule will not have substantial direct
effects on tribal governments, on the
relationship between the Federal
Government and Indian tribes, or on the
distribution of power and
responsibilities between the Federal
Government and Indian tribes, as
specified in Executive Order 13175.
Thus, Executive Order 13175 does not
apply to this rule.
IX. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., as added by the Small
Business Regulatory Enforcement
Fairness Act of 1996, generally provides
that before a rule may take effect, the
E:\FR\FM\01NOR1.SGM
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64132
Federal Register / Vol. 71, No. 211 / Wednesday, November 1, 2006 / Rules and Regulations
agency promulgating the rule must
submit a rule report, which includes a
copy of the rule, to each House of the
Congress and to the Comptroller General
of the United States. EPA will submit a
report containing this rule and other
required information to the U.S. Senate,
the U.S. House of Representatives, and
the Comptroller General of the United
States prior to publication of this final
rule in the Federal Register. This final
rule is not a ‘‘major rule’’ as defined by
5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
Dated: September 29, 2006.
James Jones,
Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
I
PART 174—AMENDED
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 174.456 is revised to read
as follows:
I
§ 174.456 Bacillus thuringiensis modified
Cry3A protein (mCry3A) and the genetic
material necessary for its production in
corn.
Bacillus thuringiensis modified Cry3A
protein (mCry3A) and the genetic
material necessary for its production in
corn is exempt from the requirement of
a tolerance when used as plantincorporated protectant in the food and
feed commodities of field corn, sweet
corn and popcorn. Genetic material
necessary for its production means the
genetic material which comprise genetic
material encoding the mCry3A protein
and its regulatory regions. Regulatory
regions are the genetic material, such as
promoters, terminators, and enhancers,
that control the expression of the
genetic material encoding the mCry3A
protein.
[FR Doc. E6–18223 Filed 10–31–06; 8:45 am]
hsrobinson on PROD1PC76 with RULES
BILLING CODE 6560–50–S
19:00 Oct 31, 2006
Federal Emergency Management
Agency
44 CFR Part 67
Final Flood Elevation Determinations
Federal Emergency
Management Agency (FEMA),
Department of Homeland Security,
Mitigation Division.
ACTION: Final rule.
AGENCY:
SUMMARY: Base (1% annual chance)
Flood Elevations (BFEs) and modified
BFEs are made final for the
communities listed below. The BFEs
and modified BFEs are the basis for the
floodplain management measures that
each community is required either to
adopt or to show evidence of being
already in effect in order to qualify or
remain qualified for participation in the
National Flood Insurance Program
(NFIP).
The date of issuance of
the Flood Insurance Rate Map (FIRM)
showing BFEs and modified BFEs for
each community. This date may be
obtained by contacting the office where
the maps are available for inspection as
indicated on the table below.
ADDRESSES: The final BFEs for each
community are available for inspection
at the office of the Chief Executive
Officer of each community. The
respective addresses are listed in the
table below.
FOR FURTHER INFORMATION CONTACT:
William R. Blanton, Jr., CFM, Acting
Section Chief, Engineering Management
Section, Mitigation Division, 500 C
Street SW., Washington, DC 20472,
(202) 646–3151.
SUPPLEMENTARY INFORMATION: FEMA
makes the final determinations listed
below for the modified BFEs for each
community listed. These modified
elevations have been published in
newspapers of local circulation and
ninety (90) days have elapsed since that
publication. The Mitigation Division
Director has resolved any appeals
resulting from this notification.
This final rule is issued in accordance
with Section 110 of the Flood Disaster
EFFECTIVE DATES:
1. The authority citation for part 174
continues to read as follows:
I
VerDate Aug<31>2005
DEPARTMENT OF HOMELAND
SECURITY
Jkt 211001
PO 00000
Frm 00022
Fmt 4700
Sfmt 4700
Protection Act of 1973, 42 U.S.C. 4104,
and 44 CFR part 67.
The Agency has developed criteria for
floodplain management in floodprone
areas in accordance with 44 CFR part
60.
Interested lessees and owners of real
property are encouraged to review the
proof Flood Insurance Study and FIRM
available at the address cited below for
each community. The BFEs and
modified BFEs are made final in the
communities listed below. Elevations at
selected locations in each community
are shown.
National Environmental Policy Act.
This rule is categorically excluded from
the requirements of 44 CFR Part 10,
Environmental Consideration. No
environmental impact assessment has
been prepared.
Regulatory Flexibility Act. As flood
elevation determinations are not within
the scope of the Regulatory Flexibility
Act, 5 U.S.C. 601–612, a regulatory
flexibility analysis is not required.
Regulatory Classification. This final
rule is not a significant regulatory action
under the criteria of Section 3(f) of
Executive Order 12866 of September 30,
1993, Regulatory Planning and Review,
58 FR 51735.
Executive Order 13132, Federalism.
This rule involves no policies that have
federalism implications under Executive
Order 13132.
Executive Order 12988, Civil Justice
Reform. This rule meets the applicable
standards of Executive Order 12988.
List of Subjects in 44 CFR Part 67
Administrative practice and
procedure, flood insurance, reporting
and recordkeeping requirements.
I Accordingly, 44 CFR Part 67 is
amended as follows:
PART 67—[AMENDED]
1. The authority citation for Part 67
continues to read as follows:
I
Authority: 42 U.S.C. 4001 et seq.;
Reorganization Plan No. 3 of 1978, 3 CFR,
1978 Comp., p. 329; E.O. 12127, 44 FR 19367,
3 CFR, 1979 Comp., p. 376.
§ 67.11
[Amended]
2. The tables published under the
authority of § 67.11 are amended as
follows:
I
E:\FR\FM\01NOR1.SGM
01NOR1
]]>Agencies
[Federal Register Volume 71, Number 211 (Wednesday, November 1, 2006)]
[Rules and Regulations]
[Pages 64128-64132]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E6-18223]
[[Page 64128]]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 174
[EPA-HQ-OPP-2006-0784; FRL-8096-4]
Bacillus Thuringiensis Modified Cry3A Protein and the Genetic
Material Necessary for Its Production in Corn; Exemption from the
Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a permanent exemption from the
requirement of a tolerance for residues of the Bacillus thuringiensis
modified Cry3A protein (mCry3A) and the genetic material necessary for
its production in corn on field corn, sweet corn, and popcorn when
applied/used as a plant-incorporated protectant. Syngenta Seeds, Inc.
submitted a petition to EPA under the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act of 1996
(FQPA), requesting an exemption from the requirement of a tolerance.
This regulation eliminates the need to establish a maximum permissible
level for residues of Bacillus thuringiensis modified Cry3A protein
(mCry3A) and the genetic material necessary for its production in corn.
DATES: This regulation is effective November 1, 2006. Objections and
requests for hearings must be received on or before January 2, 2007,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2006-0784. All documents in the
docket are listed in the index for the docket. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available in the electronic docket at https://www.regulations.gov, or,
if only available in hard copy, at the OPP Regulatory Public Docket in
Rm. S-4400, One Potomac Yard (South Building), 2777 S. Crystal Drive,
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The Docket telephone
number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Mike Mendelsohn, Biopesticides and
Pollution Prevention Division (7511P), Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-8715; e-mail address: mendelsohn.mike@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at https://
www.regulations.gov, you may access this ``Federal Register'' document
electronically through the EPA Internet under the ``Federal Register''
listings at https://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of 40 CFR part 180 through the
Government Printing Office's pilot e-CFR site at https://
www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. You must file your objection or
request a hearing on this regulation in accordance with the
instructions provided in 40 CFR part 178. To ensure proper receipt by
EPA, you must identify docket ID number EPA-HQ-OPP-2006-0784 in the
subject line on the first page of your submission. All requests must be
in writing, and must be mailed or delivered to the Hearing Clerk on or
before January 2, 2007.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit your copies, identified by docket ID
number EPA-HQ-OPP-2006-0784, by one of the following methods.
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of October 27, 2004 (69 FR 62688) (FRL-
7370-1), EPA issued a notice pursuant to section 408(d)(3) of the
FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide
tolerance petition (PP 4F6838) by Syngenta Seeds, Inc., P.O. Box 12257,
3054 Cornwallis Road, Research Triangle Park, NC 27709-2257. The
petition requested that 40 CFR part 174 be amended by establishing a
permanent exemption from the requirement of a tolerance for residues of
modified Cry3A protein (mCry3A) and the genetic material necessary for
its production in corn. This notice included a summary of the petition
prepared by the petitioner Syngenta Seeds, Inc. One comment was
received in response to the notice of filing from the National Corn
Growers Association.
[[Page 64129]]
They supported the petition and requested EPA to quickly issue the
final rule.
On March 14-15, 2006, EPA held a FIFRA Scientific Advisory Panel
(SAP) meeting, at https://www.epa.gov/scipoly/sap/meetings/2006/
index.htm#march to address the scientific issues that arose during the
risk assessment of mCry3A. EPA asked the SAP to comment on the
equivalence of the mCry3A proteins from corn event MIR604 and from
recombinant E. coli - specifically the presence of two forms in the
bacterial-produced mCry3A protein and the differences in bioactivity in
the WCRM bioassay. The majority of the Panel concluded that the two
forms of the mCry3A are of relatively comparable biological activity
for the purposes of the human health assessments based on the amino
acid sequence identity, lack of glycosylation, and general stability.
EPA also asked the SAP to comment on EPA's conclusions regarding
the lack of mammalian toxicity and allergenicity of the mCry3A protein-
specifically the impact of the less potent mCry3A form on the results
of the acute oral toxicity tests and the usefulness of in vitro
digestibility studies and amino acid sequence homology analysis as part
of the risk assessment. Overall, the Panel was more concerned with the
quality of data, i.e. inadequately described methods and poor
reproduction of data images. The Panel specifically noted that the
amino acid sequence analysis to known toxins and allergens were missing
the following data: Specification of which version of NCBI database was
utilized; descriptions of parameters utilized; and dates accessed for
the BLAST search. EPA recognizes that these are important parameters to
include in a description of an amino acid analysis and is requiring
submission of additional information by Syngenta Seeds, Inc. in order
to confirm the method used. However, EPA maintains that the conclusions
of the amino acid sequence analysis are still valid for the purpose of
the risk assessment. EPA reached this decision based on the following:
(1) Lack of mammalian toxicity of mCry3A protein as shown by the acute
oral mouse study; (2) mCry3A protein is rapidly digested in SGF; (3)
mCry3A protein originates from a non-allergenic source; (4) lack of
sequence identity of mCry3A protein with eight contiguous amino acids
or more than 35% identity over 80 amino acids with known toxins or
allergens; and (5) mCry3A protein is not glycosylated when expressed in
corn.
Section 408(c)(2)(A)(i) of the FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of the FFDCA
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.'' This includes
exposure through drinking water and in residential settings, but does
not include occupational exposure. Pursuant to section 408(c)(2)(B), in
establishing or maintaining in effect an exemption from the requirement
of a tolerance, EPA must take into account the factors set forth in
section 408(b)(2)(C), which require EPA to give special consideration
to exposure of infants and children to the pesticide chemical residue
in establishing a tolerance 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. . . .''
Additionally, section 408(b)(2)(D) of the FFDCA requires that the
Agency consider ``available information concerning the cumulative
effects of a particular pesticide's residues '' and ``other substances
that have a common mechanism of toxicity.''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides. Second, EPA examines exposure to the pesticide
through food, drinking water, and through other exposures that occur as
a result of pesticide use in residential settings.
III. Toxicological Profile
Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed
the available scientific data and other relevant information in support
of this action and considered its validity, completeness, and
reliability and the relationship of this information to human risk. EPA
has also considered available information concerning the variability of
the sensitivities of major identifiable subgroups of consumers,
including infants and children.
Data have been submitted demonstrating the lack of mammalian
toxicity at high levels of exposure to the mCry3A protein alone. These
data demonstrate the safety of the products at levels well above
maximum possible exposure levels that are reasonably anticipated in the
crops. This is similar to the Agency position regarding toxicity and
the requirement of residue data for the microbial Bacillus
thuringiensis products from which this plant-incorporated protectant
was derived (See 40 CFR 158.740(b)(2)(i)). For microbial products,
further toxicity testing and residue data are triggered by significant
acute effects in studies such as the mouse oral toxicity study, to
verify the observed effects and clarify the source of these effects
(Tiers II and III).
An acute oral toxicity study was submitted for the mCry3A protein.
The acute oral toxicity data submitted support the prediction that the
mCry3A protein would be non-toxic to humans. Male and female mice (5 of
each) were dosed with 2,377 milligrams/kilograms bodyweight (mg/kg bwt)
of mCry3A protein. With the exception of one female in the test group
that was euthanized on day 2 (due to adverse clinical signs consistent
with a dosing injury), all other mice survived the study, gained
weight, had no test material-related clinical signs, and had no test
material-related findings at necropsy.
When proteins are toxic, they are known to act via acute mechanisms
and at very low dose levels (Sjoblad, Roy D., et al. ``Toxicological
Considerations for Protein Components of Biological Pesticide
Products,'' Regulatory Toxicology and Pharmacology 15, 3-9 (1992)).
Therefore, since no effects were shown to be caused by the plant-
incorporated protectants, even at relatively high dose levels, the
mCry3A protein is not considered toxic. Further, amino acid sequence
comparisons showed no similarity between the mCry3A protein and known
toxic proteins available in public protein data bases. According to the
Codex Alimintarius guidelines, the assessment of potential toxicity
also includes stability to heat (FAO/WHO Standards Programme, 2001).
Further data demonstrate that mCry3A is inactivated against Western
corn rootworm, when heated to 95 [deg]C for 30 minutes.
Since mCry3A is a protein, allergenic sensitivities were
considered. Current scientific knowledge suggests that common food
allergens tend to be resistant to degradation by acid, and proteases;
may be glycosylated; and present at high concentrations in the food.
Data have been submitted that demonstrate that the mCry3A protein is
rapidly degraded by gastric fluid in vitro. In a solution of simulated
gastric fluid 1 milligrams/milliliter (mg/mL) mCry3A test protein mixed
with simulated gastric fluid (pH 1.2, containing 2 mg/mL NaCl, 14 [mu]L
6 N HCl, and 2.7 mg/mL pepsin) resulting in 10 pepsin activity units/
microgram ([mu]g) protein (complies with year 2000 U.S. Pharmacopoeia
recommendations),
[[Page 64130]]
complete degradation of detectable mCry3A protein occurred within 2
minutes. A comparison of amino acid sequences of known allergens
uncovered no evidence of any homology with mCry3A, even at the level of
eight contiguous amino acids residues. Further, data demonstrate that
mCry3A is not glycosylated, and is present in low levels in corn
tissue. Therefore, the potential for the mCry3A protein to be a food
allergen is minimal. As noted above, toxic proteins typically act as
acute toxins with low dose levels. Therefore, since no effects were
shown to be caused by the plant-incorporated protectant, even at
relatively high dose levels, the mCry3A protein is not considered
toxic.
IV. Aggregate Exposures
In examining aggregate exposure, section 408 of the FFDCA directs
EPA to consider available information concerning exposures from the
pesticide residue in food and all other non-occupational exposures,
including drinking water from ground water or surface water and
exposure through pesticide use in gardens, lawns, or buildings
(residential and other indoor uses).
The Agency has considered available information on the aggregate
exposure levels of consumers (and major identifiable subgroups of
consumers) to the pesticide chemical residue and to other related
substances. These considerations include dietary exposure under the
tolerance exemption and all other tolerances or exemptions in effect
for the plant-incorporated protectant chemical residue, and exposure
from non-occupational sources. Exposure via the skin or inhalation is
not likely since the plant-incorporated protectant is contained within
plant cells, which essentially eliminates these exposure routes or
reduces these exposure routes to negligible. Exposure via residential
or lawn use to infants and children is also not expected because the
use sites for the mCry3A protein are all agricultural for control of
insects. Oral exposure, at very low levels, may occur from ingestion of
processed corn products and, potentially, drinking water. However, oral
toxicity testing done at a dose in excess of 2 grams/kilogram (gm/kg)
showed no adverse effects. Furthermore, the expression of the modified
Cry3A protein in corn kernals has been shown to be in the parts per
million range, which makes the expected dietary exposure several orders
of magnitude lower than the amounts of mCry3A protein shown to have no
toxicity. Therefore, even if negligible aggregate exposure should
occur, the Agency concludes that such exposure would present reasonable
certainty of no harm due to the lack of mammalian toxicity and the
rapid digestibility demonstrated for the mCry3A protein.
V. Cumulative Effects
Pursuant to FFDCA section 408(b)(2)(D)(v), EPA has considered
available information on the cumulative effects of such residues and
other substances that have a common mechanism of toxicity. These
considerations included the cumulative effects on infants and children
of such residues and other substances with a common mechanism of
toxicity. Because there is no indication of mammalian toxicity,
resulting from the plant-incorporated protectant, we conclude that
there are no cumulative effects for the mCry3A protein.
VI. Determination of Safety for U.S. Population, Infants and Children
A. Toxicity and Allergenicity Conclusions
The data submitted and cited regarding potential health effects for
the mCry3A protein include the characterization of the expressed mCry3A
protein in corn, as well as the acute oral toxicity, and in vitro
digestibility of the proteins. The results of these studies were
determined applicable to evaluate human risk, and the validity,
completeness, and reliability of the available data from the studies
were considered.
Adequate information was submitted to show that the mCry3A protein
test material derived from microbial cultures was biochemically and
functionally similar to the protein produced by the plant-incorporated
protectant ingredients in corn. Production of microbially produced
protein was chosen in order to obtain sufficient material for testing.
The acute oral toxicity data submitted supports the prediction that
the mCry3A protein would be non-toxic to humans. As mentioned above,
when proteins are toxic, they are known to act via acute mechanisms and
at very low dose levels (Sjoblad, Roy D., et al. ``Toxicological
Considerations for Protein Components of Biological Pesticide
Products,'' Regulatory Toxicology and Pharmacology 15, 3-9 (1992)).
Since no effects were shown to be caused by mCry3A protein, even at
relatively high dose levels (2,377 mg/kg bwt), the mCry3A protein is
not considered toxic. This is similar to the Agency position regarding
toxicity and the requirement of residue data for the microbial Bacillus
thuringiensis products from which this plant-incorporated protectant
was derived. (See 40 CFR 158.740(b)(2)(i). Moreover, mCry3A showed no
sequence similarity to any known toxin and was inactivated by heat
against Western corn rootworm. No further toxicity testing and residue
data were required because for microbial products, further toxicity
testing and residue data requirements are triggered by significant
acute effects in studies such as the mouse oral toxicity study to
verify the observed effects and clarify the source of these effects
(Tiers II and III).
Modified Cry3A protein residue chemistry data were not required for
a human health effects assessment of the subject plant-incorporated
protectant ingredients because of the lack of mammalian toxicity.
However, data submitted demonstrated low levels of mCry3A in corn
tissues with less than 2 [mu]g mCry3A protein/gram dry weight in
kernals and less than 30 [mu]g mCry3A protein/gram dry weight of whole
corn plant.
Since modified Cry3A is a protein, its potential allergenicity is
also considered as part of the toxicity assessment. Data considered as
part of the allergenicity assessment include that the modified Cry3A
protein came from Bacillus thuringiensis which is not a known
allergenic source, showed no sequence similarity to known allergens,
was readily degraded by pepsin, and was not glycosylated when expressed
in the plant. Therefore, there is a reasonable certainty that modified
Cry3A protein will not be an allergen.
Neither available information concerning the dietary consumption
patterns of consumers (and major identifiable subgroups of consumers
including infants and children) nor safety factors that are generally
recognized as appropriate for the use of animal experimentation data
were evaluated. The lack of mammalian toxicity at high levels of
exposure to the mCry3A protein, as well as the minimal potential to be
a food allergen demonstrate the safety of the product at levels well
above possible maximum exposure levels anticipated in the crop.
The genetic material necessary for the production of the plant-
incorporated protectant active ingredients are the nucleic acids (DNA,
RNA) which comprise genetic material encoding these proteins and their
regulatory regions. The genetic material (DNA, RNA), necessary for the
production of mCry3A protein has been exempted under the blanket
exemption for all nucleic acids (40 CFR 174.475).
[[Page 64131]]
B. Infants and Children Risk Conclusions
FFDCA section 408(b)(2)(C) provides that EPA shall assess the
available information about consumption patterns among infants and
children, special susceptibility of infants and children to pesticide
chemical residues and the cumulative effects on infants and children of
the residues and other substances with a common mechanism of toxicity.
In addition, FFDCA section 408(b)(2)(C) also provides that EPA
shall apply an additional tenfold margin of safety, also referred to as
margins of exposure (MOEs), for infants and children in the case of
threshold effects to account for prenatal and postnatal toxicity and
the completeness of the data base unless EPA determines that a
different MOE will be safe for infants and children.
In this instance, based on all the available information, the
Agency concludes that there is a finding of no toxicity for the mCry3A
protein and the genetic material necessary for their production. Thus,
there are no threshold effects of concern to infants and children when
the mCry3A protein is used as a plant-incorporated protectant.
Accordingly, the Agency concludes that the additional MOE is not
necessary to protect infants and children, and that not adding any
additional MOE will be safe for infants and children.
C. Overall Safety Conclusion
There is a reasonable certainty that no harm will result from
aggregate exposure to the U.S. population, including infants and
children, to the mCry3A protein and the genetic material necessary for
its production. This includes all anticipated dietary exposures and all
other exposures for which there is reliable information.
The Agency has arrived at this conclusion because, as discussed
above, no toxicity to mammals has been observed, nor any indication of
allergenicity potential for the plant-incorporated protectant.
VII. Other Considerations
A. Endocrine Disruptors
The pesticidal active ingredient is a protein, derived from sources
that are not known to exert an influence on the endocrine system.
Therefore, the Agency is not requiring information on the endocrine
effects of the plant-incorporated protectant at this time.
B. Analytical Method(s)
A method for extraction and ELISA analysis of mCry3A protein in
corn has been submitted and found acceptable by the Agency.
C. Codex Maximum Residue Level
No Codex maximum residue levels exist for the plant-incorporated
protectant Bacillus thuringiensis mCry3A protein and the genetic
material necessary for its production in corn.
VIII. Statutory and Executive Order Reviews
This final rule establishes an exemption from the requirement of a
tolerance under section 408(d) of the FFDCA in response to a petition
submitted to the Agency. The Office of Management and Budget (OMB) has
exempted these types of actions from review under Executive Order
12866, entitled Regulatory Planning and Review (58 FR 51735, October 4,
1993). Because this rule has been exempted from review under Executive
Order 12866 due to its lack of significance, this rule is not subject
to Executive Order 13211, Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355,
May 22, 2001). This final rule does not contain any information
collections subject to OMB approval under the Paperwork Reduction Act
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or
contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor
does it require any special considerations under Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994);
or OMB review or any Agency action under Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997). This action does not
involve any technical standards that would require Agency consideration
of voluntary consensus standards pursuant to section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (NTTAA),
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are established on the basis of a
petition under section 408(d) of the FFDCA, such as the exemption from
the requirement of a tolerance in this final rule, do not require the
issuance of a proposed rule, the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply. In addition,
the Agency has determined that this action will not have a substantial
direct effect on States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government, as specified
in Executive Order 13132, entitled Federalism (64 FR 43255, August 10,
1999). Executive Order 13132 requires EPA to develop an accountable
process to ensure ``meaningful and timely input by State and local
officials in the development of regulatory policies that have
federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive order to include regulations
that have ``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency
has determined that this rule does not have any ``tribal implications''
as described in Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000). Executive Order 13175, requires EPA to develop an accountable
process to ensure ``meaningful and timely input by tribal officials in
the development of regulatory policies that have tribal implications.''
``Policies that have tribal implications'' is defined in the Executive
order to include regulations that have ``substantial direct effects on
one or more Indian tribes, on the relationship between the Federal
Government and the Indian tribes, or on the distribution of power and
responsibilities between the Federal Government and Indian tribes.''
This rule will not have substantial direct effects on tribal
governments, on the relationship between the Federal Government and
Indian tribes, or on the distribution of power and responsibilities
between the Federal Government and Indian tribes, as specified in
Executive Order 13175. Thus, Executive Order 13175 does not apply to
this rule.
IX. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the
[[Page 64132]]
agency promulgating the rule must submit a rule report, which includes
a copy of the rule, to each House of the Congress and to the
Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: September 29, 2006.
James Jones,
Director, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 174--AMENDED
0
1. The authority citation for part 174 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Section 174.456 is revised to read as follows:
Sec. 174.456 Bacillus thuringiensis modified Cry3A protein (mCry3A)
and the genetic material necessary for its production in corn.
Bacillus thuringiensis modified Cry3A protein (mCry3A) and the
genetic material necessary for its production in corn is exempt from
the requirement of a tolerance when used as plant-incorporated
protectant in the food and feed commodities of field corn, sweet corn
and popcorn. Genetic material necessary for its production means the
genetic material which comprise genetic material encoding the mCry3A
protein and its regulatory regions. Regulatory regions are the genetic
material, such as promoters, terminators, and enhancers, that control
the expression of the genetic material encoding the mCry3A protein.
[FR Doc. E6-18223 Filed 10-31-06; 8:45 am]
BILLING CODE 6560-50-S
