Bacillus thuringiensis Modified Cry1Ab Protein; Exemption from the Requirement of a Tolerance, 40760-40764 [E8-16277]
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40760
Federal Register / Vol. 73, No. 137 / Wednesday, July 16, 2008 / Rules and Regulations
Actions Concerning Regulations That
Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May
22, 2001) or Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
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., 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).
Since tolerances and exemptions that
are established on the basis of a petition
under section 408(d) of FFDCA, such as
the 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.
This final rule directly regulates
growers, food processors, food handlers,
and food retailers, not States or tribes,
nor does this action alter the
relationships or distribution of power
and responsibilities established by
Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such,
the Agency has determined that this
action will not have a substantial direct
effect on States or tribal governments,
on the relationship between the national
government and the States or tribal
governments, or on the distribution of
power and responsibilities among the
various levels of government or between
the Federal Government and Indian
tribes. Thus, the Agency has determined
that Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999) and Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply
to this final rule. In addition, this final
rule does not 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).
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).
X. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., generally provides
that before a rule may take effect, the
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agency promulgating the rule must
submit a rule report 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 174
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
Dated: June 10, 2008.
Janet L. Andersen,
Director, Biopesticides and Pollution
Prevention Division, Office of Pesticide
Programs.
Therefore, 40 CFR chapter I is
amended as follows:
I
PART 174—[AMENDED]
1. The authority citation for part 174
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 174.502 to subpart D is
revised to read as follows:
I
§ 174.502 Bacillus thuringiensis Cry
1A.105 protein in corn; exemption from the
requirement of a tolerance.
Residues of Bacillus thuringiensis Cry
1A.105 protein in or on the food and
feed commodities of corn; corn, field;
corn, sweet; and corn, pop, are exempt
from the requirement of a tolerance
when the Bacillus thuringiensis Cry
1A.105 protein is used as a plant–
incorporated protectant in those food
and feed corn commodities.
[FR Doc. E8–15836 Filed 7–15–08; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 174
[EPA–HQ–OPP–2007–1204; FRL–8371–6]
Bacillus thuringiensis Modified Cry1Ab
Protein; Exemption from the
Requirement of a Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes an
exemption from the requirement of a
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tolerance for residues of the Bacillus
thuringiensis modified Cry1Ab protein
as identified under OECD Unique
Identifier SYN–IR67B–1 when used as a
plant-incorporated protectant in the
food and feed commodities of cotton;
cotton, undelinted seed; cotton, refined
oil; cotton, meal; cotton, hay; cotton,
hulls; cotton, forage; and cotton, gin
byproducts. 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 Cry1Ab protein as identified
under OECD Unique Identifier SYN–
IR67B–1 when used as a plantincorporated protectant in cotton.
DATES: This regulation is effective July
16, 2008. Objections and requests for
hearings must be received on or before
September 15, 2008, 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–2007–1204. To access the
electronic docket, go to https://
www.regulations.gov, select ‘‘Advanced
Search,’’ then ‘‘Docket Search.’’ Insert
the docket ID number where indicated
and select the ‘‘Submit’’ button. Follow
the instructions on the regulations.gov
website to view the docket index or
access available documents. All
documents in the docket are listed in
the docket index available in
regulations.gov. 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 Bldg.),
2777 S. Crystal Dr., Arlington, VA. The
Docket Facility is open from 8:30 a.m.
to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket
Facility telephone number is (703) 305–
5805.
FOR FURTHER INFORMATION CONTACT:
Alan Reynolds, Biopesticides and
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Pollution Prevention Division (7511P),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 605–0515; e-mail address:
reynolds.alan@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 174
through the Government Printing
Office’s pilot e-CFR site at https://
www.gpoaccess.gov/ecfr.
dwashington3 on PRODPC61 with RULES
C. Can I File an Objection or Hearing
Request?
Under section 408(g) of FFDCA, as
amended by 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
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provided in 40 CFR part 178. To ensure
proper receipt by EPA, you must
identify docket ID number EPA–HQ–
OPP–2007–1204 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 September 15, 2008.
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–2007–1204, 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 Bldg.), 2777 S.
Crystal Dr., 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 Facility telephone number is
(703) 305–5805.
II. Background and Statutory Findings
In the Federal Register of January 30,
2008 (73 FR 5563) (FRL–8348–4), EPA
issued a notice pursuant to section
408(d)(3) of FFDCA, 21 U.S.C.
346a(d)(3), announcing the filing of a
pesticide tolerance petition (PP 7F7290)
by Syngenta Seeds, Inc., P.O. Box
12257, 3054 E. Cornwallis Road,
Research Triangle Park, NC 27709. The
petition requested that 40 CFR part 174
be amended by establishing an
exemption from the requirement of a
tolerance for residues of Bacillus
thuringiensis modified Cry1Ab protein
containing an additional 26 amino acid
sequence (‘‘Geiser Motif’’) in all crops
and agricultural commodities. A
summary of the petition prepared by the
petitioner, Syngenta Seeds, Inc., was
posted on www.regulations.gov in the
docket for this action (EPA–HQ–OPP–
2007–1204). After review, the Agency
determined that the appropriate
designation for the protein is Bacillus
thuringiensis modified Cry1Ab protein
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40761
as identified under OECD Unique
Identifier SYN–IR67B–1 (hereafter
referred to as modified Cry1Ab). There
was one comment received in response
to the notice of filing. The commenter
objected to the petition, pesticide
residues on food crops, and the
widespread use of Bacillus thuringiensis
(Bt). The Agency understands the
commenter’s concerns regarding
tolerances of pesticide residues on food.
Pursuant to its authority under the
FFDCA, EPA conducted a
comprehensive assessment of modified
Cry1Ab protein, including a review of
acute oral toxicity data on modified
Cry1Ab protein, amino acid sequence
comparisons to known toxins and
allergens, as well as data demonstrating
that modified Cry1Ab protein is rapidly
degraded by gastric fluid in vitro, is not
glycosylated, and is present in low
levels in plant tissues. Based on these
data, the Agency has concluded that
there is a reasonable certainty that no
harm will result from dietary exposure
to this protein as expressed in plantincorporated protectants. Thus, under
the standard in FFDCA section
408(b)(2), a tolerance exemption is
appropriate.
In taking this action, EPA, pursuant to
its authority under section
408(d)(4)(A)(i) of the FFDCA, is issuing
a final regulation that varies from the
regulation sought by petitioner Syngenta
Seeds, Inc. Specifically, instead of
issuing a tolerance exemption that
covers residues of the subject plantincorporated protectant in all food
commodities, EPA is issuing a tolerance
exemption that covers such residues in
those commodities in which it will be
used as a plant-incorporated protectant
– in this case, the food and feed
commodities of cotton; cotton,
undelinted seed; cotton, refined oil;
cotton, meal; cotton, hay; cotton, hulls;
cotton, forage; and cotton, gin
byproducts. In this way, the tolerance
exemption is coextensive with the
registered uses for this particular plantincorporated protectant.
Section 408(c)(2)(A)(i) of 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 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
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occupational exposure. Pursuant to
section 408(c)(2)(B) of FFDCA, 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) of FFDCA, 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
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.
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III. Toxicological Profile
Consistent with section 408(b)(2)(D)
of 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.
Mammalian Toxicity and Allergenicity
Assessment
Syngenta Seeds, Inc. has submitted
acute oral toxicity data demonstrating
the lack of mammalian toxicity at high
levels of exposure to the pure modified
Cry1Ab protein as identified under the
Organisation for Economic Co-operation
and Development (OECD) Unique
Identifier SYN–IR67B–1 (hereafter
referred to as modified Cry1Ab). The
modified Cry1Ab protein contains a 26
amino acid sequence that is found at the
C-terminus of the pro-toxin portion of
the modified Cry1Ab protein. This
sequence naturally occurs in Cry1Ab
protein expressed in microbial Bacillus
thuringiensis (Bt). The pro-toxin
containing the additional 26 amino acid
sequence is enzymatically cleaved in
the insect gut to produce active Cry1Ab.
These toxicity data demonstrate the
safety of the product at a level well
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above maximum possible exposure
levels that are reasonably anticipated in
the crop. Basing this conclusion on
acute oral toxicity data without
requiring further toxicity testing and
residue data is similar to the Agency
position regarding toxicity testing and
the requirement of residue data for the
microbial Bacillus thuringiensis
products from which this plantincorporated protectant was derived
(See 40 CFR 158.2140). For microbial
products, further toxicity testing (Tiers
II and III) and residue data are triggered
by significant adverse acute effects in
studies such as the acute oral toxicity
study, to verify the observed adverse
effects and clarify the source of these
effects.
An acute oral toxicity study in mice
indicated that modified Cry1Ab is nontoxic to humans. Groups of five male
and five female mice were given 0 or
1,830 mg/kg bodyweight microbiallyproduced modified Cry1Ab by oral
gavage as a single dose. There were no
effects on clinical condition, body
weight, food consumption, clinical
pathology, organ weight, or macroscopic
or microscopic pathology that were
attributed to the test substance.
When proteins are toxic, they are
known to act via acute mechanisms and
at very low dose levels (Ref. 1).
Therefore, since no acute effects were
shown to be caused by modified
Cry1Ab, even at relatively high dose
levels, the modified Cry1Ab protein is
not considered toxic.
Since modified Cry1Ab is a protein,
allergenic potential was also considered.
Currently, no definitive tests for
determining the allergenic potential of
novel proteins exist. Therefore, EPA
uses a weight-of- evidence approach
where the following factors are
considered: source of the trait; amino
acid sequence comparison with known
allergens; and biochemical properties of
the protein, including in vitro
digestibility in simulated gastric fluid
(SGF) and glycosylation. This approach
is consistent with the approach outlined
in the Annex to the Codex Alimentarius
‘‘Guideline for the Conduct of Food
Safety Assessment of Foods Derived
from Recombinant-DNA Plants.’’ The
allergenicity assessment for modified
Cry1Ab follows:
1. Source of the trait. Bacillus
thuringiensis is not considered to be a
source of allergenic proteins.
2. Amino acid sequence. A
comparison of the amino acid sequence
of modified Cry1Ab with known
allergens showed no significant
sequence identity over 80 amino acids
or identity at the level of 8 contiguous
amino acid residues.
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3. Digestibility. Modified Cry1Ab was
rapidly digested in simulated gastric
fluid containing pepsin.
4. Glycosylation. Modified Cry1Ab
expressed in cotton was shown not to be
glycosylated.
5. Conclusion. Considering all of the
available information, EPA has
concluded that the potential for
modified Cry1Ab to be a food allergen
is minimal.
Although modified Cry1Ab was only
shown not to be glycosylated in cotton,
it is unlikely to be glycosylated in any
other crops because in order for a
protein to be glycoslyated, it needs to
contain specific recognition sites for the
enzymes involved in glycosylation, and
the mechanisms of protein glycosylation
are similar in different plants (Ref. 2).
IV. Aggregate Exposures
In examining aggregate exposure,
section 408 of 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 (i.e., the
modified Cry1Ab protein) and to other
related substances. These considerations
include dietary exposure under the
tolerance exemption and all other
exposures from non-occupational
sources. Exposure via the skin or
inhalation is not likely since the plantincorporated protectant is contained
within plant cells, which essentially
eliminates these exposure routes or
reduces these exposure routes to
negligible. In addition, even if exposure
can occur through inhalation, the
potential for modified Cry1Ab to be an
allergen is low, as discussed above.
Although the allergenicity assessment
focuses on potential to be a food
allergen, the data also indicate a low
potential for modified Cry1Ab to be an
inhalation allergen. Exposure via
residential or lawn use to infants and
children is also not expected because
the use sites for the modified Cry1Ab
protein is agricultural. Dietary exposure
may occur from ingestion of processed
cotton products but is expected to be
very low because the already low
expression levels in the seed would be
reduced further by the heat and pressure
used for processing. Also, dietary
exposure may theoretically occur
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through exposure in drinking water
because plant stubble may release
modified Cry1Ab protein into ground
water upon decay. This protein would
not be expected to survive in the soil
due to microbial degradation, adherence
to soil components and removal upon
exposure to drinking water treatment
procedures. In addition, oral toxicity
testing showed no adverse effects.
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 from the plantincorporated protectant, there is no
common mechanism of toxicity for this
protein; therefore, section
408(b)(2)(D)(v) does not apply.
VI. Determination of Safety for U.S.
Population, Infants and Children
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A. Toxicity and Allergenicity
Conclusions
The data submitted and cited
regarding potential health effects for the
modified Cry1Ab protein includes the
characterization of the expressed
modified Cry1Ab protein in cotton, as
well as the acute oral toxicity study,
amino acid sequence comparisons to
known allergens, and in vitro
digestibility of the protein. The results
of these studies were used to evaluate
human risk, and the validity,
completeness, and reliability of the
available data from the studies were also
considered.
Adequate information was submitted
to show that the modified Cry1Ab test
material derived from microbial culture
was biochemically and functionally
equivalent to the protein in the plant.
Microbially produced protein was used
in the safety studies so that sufficient
material for testing was available.
The acute oral toxicity data submitted
support the prediction that the modified
Cry1Ab protein is 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
(Ref. 1). Since no treatment-related
adverse effects were shown to be caused
by the Cry1Ab protein, even at relatively
high dose levels, the modified Cry1Ab
protein is not considered toxic. Basing
this conclusion on acute oral toxicity
data without requiring further toxicity
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testing and residue data is similar to the
Agency position regarding toxicity and
the requirement of residue data for the
microbial Bacillus thuringiensis
products from which this plantincorporated protectant was derived
(See 40 CFR 158.2140). For microbial
products, further toxicity testing and
residue data are triggered when
significant adverse effects are seen in
studies such as the acute oral toxicity
study. Further studies verify the
observed adverse effects and clarify the
source of these effects.
Residue chemistry data were not
required for a human health effects
assessment of the subject plantincorporated protectant ingredients
because of the lack of mammalian
toxicity. However, data submitted
demonstrated low levels of the modified
Cry1Ab protein in cotton tissues.
Since Cry1Ab is a protein, potential
allergenicity is also considered as part
of the toxicity assessment. Considering
all of the available information (1)
modified Cry1Ab originates from a nonallergenic source; (2) modified Cry1Ab
has no sequence similarities with
known allergens; (3) modified Cry1Ab is
not glycosylated; and (4) modified
Cry1Ab is rapidly digested in simulated
gastric fluid; EPA has concluded that
the potential for modified Cry1Ab to be
an allergen is minimal.
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
modified Cry1Ab protein, as well as the
minimal potential to be an allergen,
demonstrate the safety of the product at
levels well above possible maximum
exposure levels anticipated.
The genetic material necessary for the
production of the plant-incorporated
protectant active ingredient include the
nucleic acids (DNA, RNA) that encode
these proteins and regulatory regions.
The genetic material (DNA, RNA)
necessary for the production of the
modified Cry1Ab protein has been
exempted from the requirement of a
tolerance under 40 CFR 174.507—
nucleic acids that are part of a plantincorporated protectant.
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
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40763
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 for infants and children in the
case of threshold effects to account for
prenatal and postnatal toxicity and the
completeness of the database unless
EPA determines that a different margin
of safety 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 modified Cry1Ab
protein. Thus, there are no threshold
effects of concern and, as a result, the
provision requiring an additional
margin of safety does not apply. Further,
the considerations of consumption
patterns, special susceptibility, and
cumulative effects do not apply.
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
modified Cry1Ab 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 a source that is
not known to exert an influence on the
endocrine system. Therefore, the
Agency is not requiring information on
the endocrine effects of this plantincorporated protectant at this time.
B. Analytical Method(s)
A lateral flow enzyme-linked
immunosorbent assay (ELISA) protocol
has been provided to the Agency for
detecting modified Cry1Ab in cotton.
C. Codex Maximum Residue Level
No Codex maximum residue level
exists for the plant-incorporated
protectant Bacillus thuringiensis
modified Cry1Ab protein.
VIII. References
1. Sjoblad, Roy D., et al.,
‘‘Toxicological Considerations for
E:\FR\FM\16JYR1.SGM
16JYR1
40764
Federal Register / Vol. 73, No. 137 / Wednesday, July 16, 2008 / Rules and Regulations
dwashington3 on PRODPC61 with RULES
Protein Components of Biological
Pesticide Products,’’ Regulatory
Toxicology and Pharmacology 15, 3–9
(1992).
2. Lerouge, P., Cabanes-Macheteau,
`
M., Rayon, C., Fichette-Laine, A-C.,
Gomord, V., and Faye, L., ‘‘NGlycoprotein biosynthesis in plants:
recent developments and future trends,’’
Plant Molecular Biology 38: 31–48
(1998).
IX. Statutory and Executive Order
Reviews
This final rule establishes a tolerance
under section 408(d) of 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 final rule
has been exempted from review under
Executive Order 12866, this final 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) or Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
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., 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).
Since tolerances and exemptions that
are established on the basis of a petition
under section 408(d) of FFDCA, such as
the 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.
This final rule directly regulates
growers, food processors, food handlers,
and food retailers, not States or tribes,
nor does this action alter the
relationships or distribution of power
and responsibilities established by
Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such,
the Agency has determined that this
action will not have a substantial direct
effect on States or tribal governments,
on the relationship between the national
government and the States or tribal
governments, or on the distribution of
power and responsibilities among the
various levels of government or between
the Federal Government and Indian
VerDate Aug<31>2005
15:04 Jul 15, 2008
Jkt 214001
tribes. Thus, the Agency has determined
that Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999) and Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply
to this final rule. In addition, this final
rule does not 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).
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).
X. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report 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 174
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
Dated: June 26, 2008.
Debra Edwards,
Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
I
PART 174—[AMENDED]
1. The authority citation for part 174
continues to read as follows:
I
Authority: 7 U.S.C. 136–136y; 21 U.S.C.
346a and 371.
2. Section 174.529 is added to subpart
W to read as follows:
I
§ 174.529 Bacillus thuringiensis modified
Cry1Ab protein as identified under OECD
Unique Identifier SYN–IR67B–1 in cotton;
exemption from the requirement of a
tolerance.
Residues of Bacillus thuringiensis
modified Cry1Ab protein as identified
PO 00000
Frm 00050
Fmt 4700
Sfmt 4700
under OECD Unique Identifier SYN–
IR67B–1 are exempt from the
requirement of a tolerance when used as
a plant-incorporated protectant in
cotton; cotton, undelinted seed; cotton,
refined oil; cotton, meal; cotton, hay;
cotton, hulls; cotton, forage; and cotton,
gin byproducts.
[FR Doc. E8–16277 Filed 7–15–08; 8:45 am]
BILLING CODE 6560–50–S
DEPARTMENT OF COMMERCE
National Oceanic and Atmospheric
Administration
50 CFR Part 679
[Docket No. 071106671–8010–02]
RIN 0648–XJ09
Fisheries of the Exclusive Economic
Zone Off Alaska; Pacific Ocean Perch
in the Western Regulatory Area of the
Gulf of Alaska
National Marine Fisheries
Service (NMFS), National Oceanic and
Atmospheric Administration (NOAA),
Commerce.
ACTION: Temporary rule; closure.
AGENCY:
SUMMARY: NMFS is prohibiting directed
fishing for Pacific ocean perch by
catcher processors participating in the
limited access or opt-out fisheries that
are subject to sideboard limits
established under the Central GOA
Rockfish Program in the Western
Regulatory Area of the Gulf of Alaska
(GOA). This action is necessary to
prevent exceeding the 2008 sideboard
limits of Pacific ocean perch established
for catcher processors participating in
the limited access or opt-out fisheries in
the Western Regulatory Area of the
GOA.
Effective 1200 hrs, Alaska local
time (A.l.t.), July 14, 2008, through 1200
hrs, A.l.t., July 31, 2008.
FOR FURTHER INFORMATION CONTACT:
Jennifer Hogan, 907–586–7228.
SUPPLEMENTARY INFORMATION: NMFS
manages the groundfish fishery in the
GOA exclusive economic zone
according to the Fishery Management
Plan for Groundfish of the Gulf of
Alaska (FMP) prepared by the North
Pacific Fishery Management Council
under authority of the MagnusonStevens Fishery Conservation and
Management Act. Regulations governing
fishing by U.S. vessels in accordance
with the FMP appear at subpart H of 50
CFR part 600 and 50 CFR part 679.
The 2008 Pacific ocean perch
sideboard limit established for catcher
DATES:
E:\FR\FM\16JYR1.SGM
16JYR1
]]>Agencies
[Federal Register Volume 73, Number 137 (Wednesday, July 16, 2008)]
[Rules and Regulations]
[Pages 40760-40764]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-16277]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 174
[EPA-HQ-OPP-2007-1204; FRL-8371-6]
Bacillus thuringiensis Modified Cry1Ab Protein; Exemption from
the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of the Bacillus thuringiensis modified
Cry1Ab protein as identified under OECD Unique Identifier SYN-IR67B-1
when used as a plant-incorporated protectant in the food and feed
commodities of cotton; cotton, undelinted seed; cotton, refined oil;
cotton, meal; cotton, hay; cotton, hulls; cotton, forage; and cotton,
gin byproducts. 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 Cry1Ab protein as identified under OECD Unique
Identifier SYN-IR67B-1 when used as a plant-incorporated protectant in
cotton.
DATES: This regulation is effective July 16, 2008. Objections and
requests for hearings must be received on or before September 15, 2008,
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-2007-1204. To access the
electronic docket, go to https://www.regulations.gov, select ``Advanced
Search,'' then ``Docket Search.'' Insert the docket ID number where
indicated and select the ``Submit'' button. Follow the instructions on
the regulations.gov website to view the docket index or access
available documents. All documents in the docket are listed in the
docket index available in regulations.gov. 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 Bldg.), 2777 S. Crystal Dr.,
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The Docket Facility
telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Alan Reynolds, Biopesticides and
[[Page 40761]]
Pollution Prevention Division (7511P), Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 605-0515; e-mail address: reynolds.alan@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 174 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 FFDCA, as amended by 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-2007-1204 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 September 15, 2008.
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-2007-1204, 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
Bldg.), 2777 S. Crystal Dr., 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 Facility telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of January 30, 2008 (73 FR 5563) (FRL-8348-
4), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance
petition (PP 7F7290) by Syngenta Seeds, Inc., P.O. Box 12257, 3054 E.
Cornwallis Road, Research Triangle Park, NC 27709. The petition
requested that 40 CFR part 174 be amended by establishing an exemption
from the requirement of a tolerance for residues of Bacillus
thuringiensis modified Cry1Ab protein containing an additional 26 amino
acid sequence (``Geiser Motif'') in all crops and agricultural
commodities. A summary of the petition prepared by the petitioner,
Syngenta Seeds, Inc., was posted on www.regulations.gov in the docket
for this action (EPA-HQ-OPP-2007-1204). After review, the Agency
determined that the appropriate designation for the protein is Bacillus
thuringiensis modified Cry1Ab protein as identified under OECD Unique
Identifier SYN-IR67B-1 (hereafter referred to as modified Cry1Ab).
There was one comment received in response to the notice of filing. The
commenter objected to the petition, pesticide residues on food crops,
and the widespread use of Bacillus thuringiensis (Bt). The Agency
understands the commenter's concerns regarding tolerances of pesticide
residues on food. Pursuant to its authority under the FFDCA, EPA
conducted a comprehensive assessment of modified Cry1Ab protein,
including a review of acute oral toxicity data on modified Cry1Ab
protein, amino acid sequence comparisons to known toxins and allergens,
as well as data demonstrating that modified Cry1Ab protein is rapidly
degraded by gastric fluid in vitro, is not glycosylated, and is present
in low levels in plant tissues. Based on these data, the Agency has
concluded that there is a reasonable certainty that no harm will result
from dietary exposure to this protein as expressed in plant-
incorporated protectants. Thus, under the standard in FFDCA section
408(b)(2), a tolerance exemption is appropriate.
In taking this action, EPA, pursuant to its authority under section
408(d)(4)(A)(i) of the FFDCA, is issuing a final regulation that varies
from the regulation sought by petitioner Syngenta Seeds, Inc.
Specifically, instead of issuing a tolerance exemption that covers
residues of the subject plant-incorporated protectant in all food
commodities, EPA is issuing a tolerance exemption that covers such
residues in those commodities in which it will be used as a plant-
incorporated protectant - in this case, the food and feed commodities
of cotton; cotton, undelinted seed; cotton, refined oil; cotton, meal;
cotton, hay; cotton, hulls; cotton, forage; and cotton, gin byproducts.
In this way, the tolerance exemption is coextensive with the registered
uses for this particular plant-incorporated protectant.
Section 408(c)(2)(A)(i) of 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 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
[[Page 40762]]
occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, 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) of FFDCA, 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 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 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.
Mammalian Toxicity and Allergenicity Assessment
Syngenta Seeds, Inc. has submitted acute oral toxicity data
demonstrating the lack of mammalian toxicity at high levels of exposure
to the pure modified Cry1Ab protein as identified under the
Organisation for Economic Co-operation and Development (OECD) Unique
Identifier SYN-IR67B-1 (hereafter referred to as modified Cry1Ab). The
modified Cry1Ab protein contains a 26 amino acid sequence that is found
at the C-terminus of the pro-toxin portion of the modified Cry1Ab
protein. This sequence naturally occurs in Cry1Ab protein expressed in
microbial Bacillus thuringiensis (Bt). The pro-toxin containing the
additional 26 amino acid sequence is enzymatically cleaved in the
insect gut to produce active Cry1Ab. These toxicity data demonstrate
the safety of the product at a level well above maximum possible
exposure levels that are reasonably anticipated in the crop. Basing
this conclusion on acute oral toxicity data without requiring further
toxicity testing and residue data is similar to the Agency position
regarding toxicity testing and the requirement of residue data for the
microbial Bacillus thuringiensis products from which this plant-
incorporated protectant was derived (See 40 CFR 158.2140). For
microbial products, further toxicity testing (Tiers II and III) and
residue data are triggered by significant adverse acute effects in
studies such as the acute oral toxicity study, to verify the observed
adverse effects and clarify the source of these effects.
An acute oral toxicity study in mice indicated that modified Cry1Ab
is non-toxic to humans. Groups of five male and five female mice were
given 0 or 1,830 mg/kg bodyweight microbially-produced modified Cry1Ab
by oral gavage as a single dose. There were no effects on clinical
condition, body weight, food consumption, clinical pathology, organ
weight, or macroscopic or microscopic pathology that were attributed to
the test substance.
When proteins are toxic, they are known to act via acute mechanisms
and at very low dose levels (Ref. 1). Therefore, since no acute effects
were shown to be caused by modified Cry1Ab, even at relatively high
dose levels, the modified Cry1Ab protein is not considered toxic.
Since modified Cry1Ab is a protein, allergenic potential was also
considered. Currently, no definitive tests for determining the
allergenic potential of novel proteins exist. Therefore, EPA uses a
weight-of- evidence approach where the following factors are
considered: source of the trait; amino acid sequence comparison with
known allergens; and biochemical properties of the protein, including
in vitro digestibility in simulated gastric fluid (SGF) and
glycosylation. This approach is consistent with the approach outlined
in the Annex to the Codex Alimentarius ``Guideline for the Conduct of
Food Safety Assessment of Foods Derived from Recombinant-DNA Plants.''
The allergenicity assessment for modified Cry1Ab follows:
1. Source of the trait. Bacillus thuringiensis is not considered to
be a source of allergenic proteins.
2. Amino acid sequence. A comparison of the amino acid sequence of
modified Cry1Ab with known allergens showed no significant sequence
identity over 80 amino acids or identity at the level of 8 contiguous
amino acid residues.
3. Digestibility. Modified Cry1Ab was rapidly digested in simulated
gastric fluid containing pepsin.
4. Glycosylation. Modified Cry1Ab expressed in cotton was shown not
to be glycosylated.
5. Conclusion. Considering all of the available information, EPA
has concluded that the potential for modified Cry1Ab to be a food
allergen is minimal.
Although modified Cry1Ab was only shown not to be glycosylated in
cotton, it is unlikely to be glycosylated in any other crops because in
order for a protein to be glycoslyated, it needs to contain specific
recognition sites for the enzymes involved in glycosylation, and the
mechanisms of protein glycosylation are similar in different plants
(Ref. 2).
IV. Aggregate Exposures
In examining aggregate exposure, section 408 of 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 (i.e., the modified Cry1Ab
protein) and to other related substances. These considerations include
dietary exposure under the tolerance exemption and all other exposures
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. In addition, even if
exposure can occur through inhalation, the potential for modified
Cry1Ab to be an allergen is low, as discussed above. Although the
allergenicity assessment focuses on potential to be a food allergen,
the data also indicate a low potential for modified Cry1Ab to be an
inhalation allergen. Exposure via residential or lawn use to infants
and children is also not expected because the use sites for the
modified Cry1Ab protein is agricultural. Dietary exposure may occur
from ingestion of processed cotton products but is expected to be very
low because the already low expression levels in the seed would be
reduced further by the heat and pressure used for processing. Also,
dietary exposure may theoretically occur
[[Page 40763]]
through exposure in drinking water because plant stubble may release
modified Cry1Ab protein into ground water upon decay. This protein
would not be expected to survive in the soil due to microbial
degradation, adherence to soil components and removal upon exposure to
drinking water treatment procedures. In addition, oral toxicity testing
showed no adverse effects.
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 from the
plant-incorporated protectant, there is no common mechanism of toxicity
for this protein; therefore, section 408(b)(2)(D)(v) does not apply.
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 modified Cry1Ab protein includes the characterization of the
expressed modified Cry1Ab protein in cotton, as well as the acute oral
toxicity study, amino acid sequence comparisons to known allergens, and
in vitro digestibility of the protein. The results of these studies
were used to evaluate human risk, and the validity, completeness, and
reliability of the available data from the studies were also
considered.
Adequate information was submitted to show that the modified Cry1Ab
test material derived from microbial culture was biochemically and
functionally equivalent to the protein in the plant. Microbially
produced protein was used in the safety studies so that sufficient
material for testing was available.
The acute oral toxicity data submitted support the prediction that
the modified Cry1Ab protein is 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 (Ref. 1). Since no treatment-related adverse
effects were shown to be caused by the Cry1Ab protein, even at
relatively high dose levels, the modified Cry1Ab protein is not
considered toxic. Basing this conclusion on acute oral toxicity data
without requiring further toxicity testing and residue data 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
158.2140). For microbial products, further toxicity testing and residue
data are triggered when significant adverse effects are seen in studies
such as the acute oral toxicity study. Further studies verify the
observed adverse effects and clarify the source of these effects.
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 the modified Cry1Ab protein in cotton
tissues.
Since Cry1Ab is a protein, potential allergenicity is also
considered as part of the toxicity assessment. Considering all of the
available information (1) modified Cry1Ab originates from a non-
allergenic source; (2) modified Cry1Ab has no sequence similarities
with known allergens; (3) modified Cry1Ab is not glycosylated; and (4)
modified Cry1Ab is rapidly digested in simulated gastric fluid; EPA has
concluded that the potential for modified Cry1Ab to be an allergen is
minimal.
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 modified Cry1Ab protein, as well as the minimal
potential to be an allergen, demonstrate the safety of the product at
levels well above possible maximum exposure levels anticipated.
The genetic material necessary for the production of the plant-
incorporated protectant active ingredient include the nucleic acids
(DNA, RNA) that encode these proteins and regulatory regions. The
genetic material (DNA, RNA) necessary for the production of the
modified Cry1Ab protein has been exempted from the requirement of a
tolerance under 40 CFR 174.507--nucleic acids that are part of a plant-
incorporated protectant.
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 for infants and children
in the case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the database unless EPA determines
that a different margin of safety 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
modified Cry1Ab protein. Thus, there are no threshold effects of
concern and, as a result, the provision requiring an additional margin
of safety does not apply. Further, the considerations of consumption
patterns, special susceptibility, and cumulative effects do not apply.
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 modified Cry1Ab 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 a
source that is not known to exert an influence on the endocrine system.
Therefore, the Agency is not requiring information on the endocrine
effects of this plant-incorporated protectant at this time.
B. Analytical Method(s)
A lateral flow enzyme-linked immunosorbent assay (ELISA) protocol
has been provided to the Agency for detecting modified Cry1Ab in
cotton.
C. Codex Maximum Residue Level
No Codex maximum residue level exists for the plant-incorporated
protectant Bacillus thuringiensis modified Cry1Ab protein.
VIII. References
1. Sjoblad, Roy D., et al., ``Toxicological Considerations for
[[Page 40764]]
Protein Components of Biological Pesticide Products,'' Regulatory
Toxicology and Pharmacology 15, 3-9 (1992).
2. Lerouge, P., Cabanes-Macheteau, M., Rayon, C., Fichette-
Lain[egrave], A-C., Gomord, V., and Faye, L., ``N-Glycoprotein
biosynthesis in plants: recent developments and future trends,'' Plant
Molecular Biology 38: 31-48 (1998).
IX. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
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 final rule has been
exempted from review under Executive Order 12866, this final 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) or Executive Order 13045, entitled Protection of
Children from Environmental Health Risks and Safety Risks (62 FR 19885,
April 23, 1997). 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., 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).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the 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.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not 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).
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).
X. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report 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 174
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: June 26, 2008.
Debra Edwards,
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: 7 U.S.C. 136-136y; 21 U.S.C. 346a and 371.
0
2. Section 174.529 is added to subpart W to read as follows:
Sec. 174.529 Bacillus thuringiensis modified Cry1Ab protein as
identified under OECD Unique Identifier SYN-IR67B-1 in cotton;
exemption from the requirement of a tolerance.
Residues of Bacillus thuringiensis modified Cry1Ab protein as
identified under OECD Unique Identifier SYN-IR67B-1 are exempt from the
requirement of a tolerance when used as a plant-incorporated protectant
in cotton; cotton, undelinted seed; cotton, refined oil; cotton, meal;
cotton, hay; cotton, hulls; cotton, forage; and cotton, gin byproducts.
[FR Doc. E8-16277 Filed 7-15-08; 8:45 am]
BILLING CODE 6560-50-S
