Bacillus Thuringiensis Vip3Aa19 Protein in Cotton; Extension of a Temporary Exemption From the Requirement of a Tolerance, 68744-68748 [E7-23660]
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Federal Register / Vol. 72, No. 234 / Thursday, December 6, 2007 / Rules and Regulations
(12) Selecting plants that tolerate air
pollution agents and toxic soil
chemicals;
(13) Selecting plants that mitigate
odor, PM–10, and PM–2.5;
(14) Testing plants for biofuels and
other energy-related activities; and
(15) Evaluating plants and techniques
to combat invasive plant species and for
reestablishment of desirable species
after eradication.
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§ 613.3 NRCS responsibilities in plant
materials.
NRCS operates or enters into
agreements with State universities or
other State organizations to operate
plant materials centers. Also, NRCS
cooperates, both formally and
informally, with other Federal, State,
county, and nonprofit agencies or
organizations on the selection of plants
and evaluation of plant technology to
increase the capabilities of plant
materials centers. NRCS employs
specialists for testing and selecting plant
materials for conservation uses and the
development of plant materials
technology. NRCS responsibilities are
to:
(a) Identify the resource conservation
needs and cultural management
methods for environmental protection
and enhancement.
(b) Assemble and comparatively
evaluate plant materials at plant
materials centers and on sites where
soil, climate, or other conditions differ
significantly from those at the centers.
(c) Make comparative field plantings
for final testing of promising plants and
techniques in cooperation with
conservation districts and other
interested cooperators.
(d) Release cooperatively improved
conservation plants and maintain the
breeder or foundation stocks in ways
appropriate for particular State and
plant species by working with
experiment stations, crop improvement
associations, and other State and
Federal agencies.
(e) Produce limited amounts of
foundation or foundation-quality seed
and plants available by grant to or by
exchange with conservation districts,
experiment stations, other Federal and
State research agencies, and State seed
certifying organizations that will use the
material to establish seed fields, seed
orchards, or plantings for vegetative
increase.
(f) Encourage and assist conservation
districts, commercial seed producers,
and commercial and State nurseries to
produce needed plant materials for
conservation uses.
(g) Encourage the use of improved
plant materials and plant materials
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technology in resource conservation and
environmental improvement programs.
ENVIRONMENTAL PROTECTION
AGENCY
§ 613.4 Special production of plant
materials.
40 CFR Part 174
NRCS can produce plant materials in
the quantity required to do a specific
conservation job if this production will
serve the public welfare and only if the
plant materials are not available
commercially. This function will be
performed only until the plant materials
are available commercially. Specific
production of plant materials by NRCS
requires the approval of the Chief.
§ 613.5
Plant materials centers.
(a) The National Plant Materials
Center. The National Plant Materials
Center at Beltsville, Maryland focuses
on national initiatives and provides
coordination for plant materials work
across all 50 States. In addition, the
center provides plants and plant
technology to address resource concerns
in the mid-Atlantic region.
(b) Other Plant Materials Centers.
There are 26 other plant materials
centers; each serves several major land
resource areas. Twenty-four of these
centers are operated by NRCS and two
by cooperating agencies as follows:
(1) Operated by NRCS: Tucson,
Arizona; Booneville, Arkansas;
Lockeford, California; Brooksville,
Florida; Americus, Georgia; Molokai,
Hawaii; Aberdeen, Idaho; Manhattan,
Kansas; Golden Meadows, Louisiana;
East Lansing, Michigan; Coffeeville,
Mississippi; Elsberry, Missouri; Bridger,
Montana; Fallon, Nevada; Cape May
Courthouse, New Jersey; Los Lunas,
New Mexico; Big Flats, New York;
Bismarck, North Dakota; Corvallis,
Oregon; Kingsville, Texas; Knox City,
Texas; Nacogdoches, Texas; Pullman,
Washington; and Alderson, West
Virginia.
(2) Operated by cooperating agencies
with financial and technical assistance
from NRCS: Meeker, Colorado—White
River and Douglas Creek Soil
Conservation Districts with partial
funding from NRCS.
(3) Operated by cooperating agencies
with technical assistance from NRCS:
Palmer, Alaska—State of Alaska,
Department of Natural Resources.
Signed in Washington, DC, on November
20, 2007.
Arlen L. Lancaster,
Chief.
[FR Doc. E7–23525 Filed 12–5–07; 8:45 am]
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[EPA–HQ–OPP–2007–0575; FRL–8340–4]
Bacillus Thuringiensis Vip3Aa19
Protein in Cotton; Extension of a
Temporary Exemption From the
Requirement of a Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation extends the
temporary exemption from the
requirement of a tolerance for residues
of the Bacillus thuringiensis Vip3Aa19
protein in cotton when applied or used
as a plant-incorporated protectant (PIP).
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 the
temporary tolerance exemption be
extended. This regulation eliminates the
need to establish a maximum
permissible level for residues of Bacillus
thuringiensis Vip3Aa19 protein in
cotton when applied or used as a PIP on
cotton. The temporary tolerance
exemption expires on May 1, 2009.
DATES: This regulation is effective
December 6, 2007. Objections and
requests for hearings must be received
on or before February 4, 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–2007–0575. 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
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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
Pollution Prevention Division (7511P),
Office of Pesticide Programs,
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.
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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.
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II. Background and Statutory Findings
exemption from the requirement of a
tolerance for residues of Bacillus
thuringiensis Vip3Aa19 insect control
protein (vector pCOT1) when applied or
used as a PIP on cotton expires on May
1, 2009. This notice included a
summary of the petition prepared by the
petitioner, Syngenta Seeds, Inc. There
were no comments received in response
to the notice of filing.
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
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.
In the Federal Register of August 8,
2007 (72 FR 44521) (FRL–8139–7), 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 7F7216)
by Syngenta Seeds, Inc., 3054
Cornwallis Rd., P.O. Box 12257,
Research Triangle Park, NC 27709. The
petition requested that 40 CFR 174.501
be amended such that the temporary
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
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–2007–0575 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 February 4, 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–2007–0575, 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.
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Federal Register / Vol. 72, No. 234 / Thursday, December 6, 2007 / Rules and Regulations
identifiable subgroups of consumers,
including infants and children.
Data have been submitted
demonstrating a lack of mammalian
toxicity at high levels of exposure to the
pure (microbially expressed) Vip3Aa19
protein. These data demonstrate the
safety of Vip3Aa19 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 PIP was derived (See 40 CFR
158.740(b)(2)(i)). For microbial
products, the need for Tier II and III
toxicity testing and residue data to
verify the observed effects and clarify
the source of these effects is triggered
only by significant acute effects in
studies such as the mouse oral toxicity
study.
In previously submitted Vip3A
studies and applications, the
designation VIP3A or Vip3A was used
to describe the Vip PIP protein and/or
test material. In the final rule, it is
necessary to distinguish the various
Vip3A designations based on the
Crickmore Bacillus thuringiensis Vip3A
nomenclature (see https://
www.lifesci.sussex.ac.uk/Home/
Neil_Crickmore/Bt). The original Vip3A
toxin as expressed in COT102 is now
known as Vip3Aa19 toxin according to
the Crickmore nomenclature
designation. A temporary exemption
from the requirement of tolerance
already has been established for the
Bacillus thuringiensis Vip3Aa19 protein
in cotton (See the Federal Register issue
of July 25, 2007 (72 FR 40752) (FRL–
8134–3); 40 CFR 174.501 that expires
May 1, 2008.
An acute oral toxicity study was
submitted for the Vip3Aa19 protein.
Male and female mice (16 of each) were
dosed with 3,675 milligrams/kilograms
bodyweight (mg/kg bwt) of Vip3Aa19
protein. All mice survived the study,
gained weight, had no test materialrelated clinical signs, and had no test
material-related findings at necropsy.
This acute oral toxicity data supports
the prediction that the Vip3Aa19
protein would be non-toxic to humans.
When proteins are toxic, they are
known to act via acute mechanisms and
at very low dose levels (Sjoblad, Roy D.,
et al. 1992). Therefore, since no effects
were shown to be caused by the PIP,
even at relatively high-dose levels, the
Vip3Aa19 protein is not considered
toxic. Amino acid sequence
comparisons showed no similarity
between the Vip3Aa19 protein and
known toxic proteins available in public
protein data bases. According to the
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Codex Alimintarius Commission
(Codex) guidelines, the assessment of
potential toxicity also includes stability
to heat (Joint Food and Agriculture
Organization of the United Nations/
World Health Organization (FAO/WHO)
Food Standard Programme, Codex
Alimentarius Commission, 20031). A
heat lability study demonstrated that
Vip3Aa19 is inactivated against fall
armyworm when heated to 55 °C for 30
minutes.
Since Vip3Aa19 is a protein,
allergenic sensitivities were considered.
Currently, no definitive tests exist for
determining the allergenic potential of
novel proteins. Therefore, EPA uses a
weight-of-the-evidence approach where
the following factors are considered:
source of the trait; amino acid sequence
similarity with known allergens;
prevalence in food; and biochemical
properties of the protein, including in
vitro digestibility in simulated gastric
fluid (SGF), and glycosylation. This
approach was described by the Codex
guidelines for the conduct of food safety
assessment of food derived from
recombinant-DNA plants including the
assessment of possible allergenicity in
2003 (Joint FAO/WHO Food Standard
Programme, Codex Alimentarius
Commission, 20031).
Data have been submitted that
demonstrate that the Vip3A from
recombinant maize (LPPACHA–0199)
and E. coli (VIP3A–0100) proteins are
rapidly degraded by gastric fluid in
vitro. (VIP3A–0100 refers to a
microbially expressed Vip3A that has
been shown to be the equivalent of the
plant-expressed Vip3A protein.) In a
solution of SGF (containing pepsin) and
either 80 microLiters (µL) of LPPACHA–
0199 or 320 µL of VIP3A–0100 test
protein, both were shown to be
susceptible to pepsin degradation.
These data support the conclusion that
Vip3A proteins expressed in transgenic
plants will be readily digested as a
conventional dietary protein under
typical mammalian gastric conditions.
Further data demonstrate that Vip3Aa19
is not glycoslylated and a comparison of
amino acid sequences of known
allergens uncovered no evidence of any
homology with Vip3Aa19, even at the
level of eight contiguous amino acid
residues. These data demonstrated that
mean Vip3Aa19 concentration in cotton
seed ranged from (circa). 2.51 to 3.23
1 Alinorm 03/34: Joint FAO/WHO Food Standard
Programme, Codex Alimentarius Commission,
Twenty-Fifth Session, Rome, Italy 30 June–5 July,
2003. Appendix III, Guideline for the conduct of
food safety assessment of foods derived from
recombinant-DNA plants and Appendix IV, Annex
on the assessment of possible allergenicity. Rome,
Codex Alimentarius Commission, 2003, p.p 47–60.
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micrograms (µg) Vip3A/g dry weight.
Vip3Aa19 was not detected in cotton
fiber or nectar. Analysis of the refined
oil and de-fatted meal by EnzymeLinked Immunosorbent Assay (ELISA)
detected Vip3Aa19 protein in COT102
meal, but not in oil. Therefore, based on
the data provided for the specific
Vip3Aa19 protein, one can conclude
that the Vip3Aa19 protein is present in
low levels in cotton seed and not
detected in cotton fiber.
Therefore, the potential for the
Vip3Aa19 protein to be a food allergen
is minimal. As noted in Unit III., toxic
proteins typically act as acute toxins
with low dose levels. Therefore, since
no effects were shown to be caused by
this PIP, even at relatively high-dose
levels, the Vip3Aa19 protein is not
considered toxic.
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 and to
other related substances. These
considerations include dietary exposure
under the tolerance exemption and all
other tolerances or exemptions in effect
for the PIP chemical residue, and
exposure from non-occupational
sources. Exposure via the skin or
inhalation is not likely since the PIP is
contained within plant cells, which
essentially eliminates these exposure
routes or reduces these exposure routes
to negligible. The amino acid homology
assessment revealed no similarities to
known aeroallergens, indicating that
Vip3A has a low potential to be an
inhalation allergen. It has been
demonstrated that there is no evidence
of occupationally related respiratory
symptoms, based on a health survey on
migrant workers after exposure to
Bacillus thuringiensis pesticides
(Berstein et al. 1999), which provides
further evidence of the negligible
respiratory risks of Bacillus
thuringiensis PIPs. Exposure via
residential or lawn use to infants and
children is also not expected because
the use sites for the Vip3Aa19 protein
are all agricultural for control of insects.
Oral exposure, at very low levels may
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occur from ingestion of processed corn
products and, theoretically, drinking
water.
However, oral toxicity testing done at
a dose in excess of 3 grams/kilogram
(gm/kg) showed no adverse effects.
Furthermore, the expected dietary
exposure from cotton is several orders of
magnitude lower than the amounts of
Vip3Aa19 protein shown to have no
toxicity. Therefore, even if negligible
aggregate exposure should occur, the
Agency concludes that such exposure
would present no harm due to the lack
of mammalian toxicity and the rapid
digestibility demonstrated for the
Vip3Aa19 proteins.
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 include 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, the Agency
concludes that there are no cumulative
effects arising from Vip3Aa19 protein
residues in cotton.
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
Vip3Aa19 protein include the
characterization of the expressed
Vip3Aa19 protein in cotton, as well as
the acute oral toxicity, heat stability,
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 Vip3A protein test
material derived from microbial cultures
(designated VIP3A–0100) was
biochemically and functionally similar
to the Vip3Aa19 protein expressed in
cotton. Microbially produced protein
was chosen in order to obtain sufficient
material for testing.
The acute oral toxicity data submitted
supports the prediction that the
Vip3Aa19 protein would be non-toxic to
humans. As mentioned in Unit III.,
when proteins are toxic, they are known
to act via acute mechanisms and at very
low-dose levels (Sjoblad, Roy D., et al.
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1992). Since no effects were shown to be
caused by Vip3Aa19 protein, even at
relatively high dose levels (3,675 mg
Vip3Aa19/kg bwt), the Vip3Aa19
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
PIP was derived. (See 40 CFR
158.740(b)(2)(i)). Moreover, Vip3Aa19
showed no sequence similarity to any
known toxin.
Protein residue chemistry data for
Vip3Aa19 were not required for a
human health effects assessment of the
subject PIP ingredients because of the
lack of mammalian toxicity. Expression
data demonstrated that mean Vip3Aa19
concentrations in cotton seed ranged
from approximately 2.51 to 3.23 µg
Vip3Aa19/g dry weight. Vip3Aa19 was
not detected in cotton fiber or nectar.
Analysis of the refined oil and de-fatted
meal by ELISA detected Vip3Aa19
protein in COT102 meal, but not in oil.
Therefore, Vip3Aa19 is present in low
levels in cotton seed and not detectable
in cotton fiber.
Since Vip3Aa19 is a protein, its
potential allergenicity is also considered
as part of the toxicity assessment.
Information considered as part of the
allergenicity assessment included data
demonstrating that the Vip3Aa19
protein came from a 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 the Vip3Aa19 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
Vip3Aa19 protein, as well as the
minimal potential to be a food allergen,
demonstrate the safety of Vip3Aa19 at
levels well above possible maximum
exposure levels anticipated in the crop.
The genetic material necessary for the
production of the PIP active ingredients
are the nucleic acids Deoxyribonucleic
acid, Ribonucleic acid (DNA, RNA)
which comprise genetic material
encoding these proteins and their
regulatory regions. The genetic material
DNA, RNA necessary for the production
of Vip3Aa19 protein already are
exempted from the requirement of a
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tolerance under a blanket exemption for
all nucleic acids (40 CFR 174.507).
B. Infants and Children Risk
Conclusions
Section 408(b)(2)(C) of FFDCA
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 data base, 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 Vip3Aa19 protein and
the genetic material necessary for its
production in cotton. Because there are
no threshold effects of concern, the
Agency has determined that the
additional tenfold margin of safety is
not necessary to protect infants and
children. Further, the provisions 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 to the U.S. population,
including infants and children, from
aggregate exposure to residues of the
Vip3Aa19 protein and the genetic
material necessary for its production in
cotton, when it is applied or used in
accordance with good agricultural
practices. 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 previously
discussed, no toxicity to mammals has
been observed, nor has there been any
indication of allergenicity potential for
this PIP.
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 PIP at this
time.
E:\FR\FM\06DER1.SGM
06DER1
68748
Federal Register / Vol. 72, No. 234 / Thursday, December 6, 2007 / Rules and Regulations
B. Analytical Method(s)
A method for extraction and ELISA
analysis of the Vip3Aa19 protein in
cotton has been submitted and is under
review by the Agency. For the
temporary tolerance exemption, the
ELISA method described with the
expression data is sufficient.
C. Codex Maximum Residue Level
No Codex maximum residue levels
exist for the PIP Bacillus thuringiensis
Vip3Aa19 protein and the genetic
material necessary for its production in
cotton.
rmajette on PROD1PC64 with RULES
VIII. Statutory and Executive Order
Reviews
This final rule extends the temporary
exemption from the requirement of 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 rule has been exempted
from review under Executive Order
12866, 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) 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 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,
VerDate Aug<31>2005
15:21 Dec 05, 2007
Jkt 214001
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 6, 2000) do not apply
to this rule. In addition, This 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).
IX. 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).
§ 174.501 Bacillus thuringiensis Vip3Aa19
protein in cotton; temporary exemption
from the requirement of a tolerance.
Residues of Bacillus thuringiensis
Vip3Aa19 protein in cotton are
temporarily exempt from the
requirement of a tolerance when used as
a plant-incorporated protectant in the
food and feed commodities of cotton;
vegetative-insecticidal protein in cotton,
undelinted seed, cotton, oil, cotton
meal, cotton hay, cotton hulls, cotton
forage, and cotton, gin byproducts. This
temporary exemption from the
requirement of tolerance will permit the
use of the food commodities in this
section when treated in accordance with
the provisions of the experimental use
permit 67979–EUP–7, which is being
extended in accordance with the
provisions of the Federal Insecticide,
Fungicide, and Rodenticide Act
(FIFRA), as amended (7 U.S.C. 136).
This temporary exemption from the
requirement of a tolerance expires and
is revoked May 1, 2009; however, if the
experimental use permit is revoked, or
if any experience with or scientific data
on this pesticide indicate that the
temporary tolerance exemption is not
safe, this temporary exemption from the
requirement of a tolerance may be
revoked at any time.
[FR Doc. E7–23660 Filed 12–5–07; 8:45 am]
BILLING CODE 6560–50–S
DEPARTMENT OF HOMELAND
SECURITY
Federal Emergency Management
Agency
44 CFR Part 64
[Docket No. FEMA–8003]
List of Subjects in 40 CFR Part 174
Suspension of Community Eligibility
Environmental protection,
Administrative practice and procedure,
Pesticides and pests, Reporting and
recordkeeping requirements.
AGENCY:
Dated: November 27, 2007.
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: 7 U.S.C. 136–136y; 21 U.S.C.
346a and 371.
2. Section 174.501 is revised to read
as follows:
I
PO 00000
Frm 00006
Fmt 4700
Sfmt 4700
Federal Emergency
Management Agency, DHS.
ACTION: Final rule.
SUMMARY: This rule identifies
communities, where the sale of flood
insurance has been authorized under
the National Flood Insurance Program
(NFIP), that are scheduled for
suspension on the effective dates listed
within this rule because of
noncompliance with the floodplain
management requirements of the
program. If the Federal Emergency
Management Agency (FEMA) receives
documentation that the community has
adopted the required floodplain
management measures prior to the
effective suspension date given in this
rule, the suspension will not occur and
a notice of this will be provided by
E:\FR\FM\06DER1.SGM
06DER1
]]>Agencies
[Federal Register Volume 72, Number 234 (Thursday, December 6, 2007)]
[Rules and Regulations]
[Pages 68744-68748]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-23660]
=======================================================================
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 174
[EPA-HQ-OPP-2007-0575; FRL-8340-4]
Bacillus Thuringiensis Vip3Aa19 Protein in Cotton; Extension of a
Temporary Exemption From the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation extends the temporary exemption from the
requirement of a tolerance for residues of the Bacillus thuringiensis
Vip3Aa19 protein in cotton when applied or used as a plant-incorporated
protectant (PIP). 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 the
temporary tolerance exemption be extended. This regulation eliminates
the need to establish a maximum permissible level for residues of
Bacillus thuringiensis Vip3Aa19 protein in cotton when applied or used
as a PIP on cotton. The temporary tolerance exemption expires on May 1,
2009.
DATES: This regulation is effective December 6, 2007. Objections and
requests for hearings must be received on or before February 4, 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-2007-0575. 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
[[Page 68745]]
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
Pollution Prevention Division (7511P), Office of Pesticide Programs,
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-2007-0575 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 February 4, 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-2007-0575, 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 August 8, 2007 (72 FR 44521) (FRL-8139-
7), 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 7F7216) by Syngenta Seeds, Inc., 3054 Cornwallis Rd., P.O.
Box 12257, Research Triangle Park, NC 27709. The petition requested
that 40 CFR 174.501 be amended such that the temporary exemption from
the requirement of a tolerance for residues of Bacillus thuringiensis
Vip3Aa19 insect control protein (vector pCOT1) when applied or used as
a PIP on cotton expires on May 1, 2009. This notice included a summary
of the petition prepared by the petitioner, Syngenta Seeds, Inc. There
were no comments received in response to the notice of filing.
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
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
[[Page 68746]]
identifiable subgroups of consumers, including infants and children.
Data have been submitted demonstrating a lack of mammalian toxicity
at high levels of exposure to the pure (microbially expressed) Vip3Aa19
protein. These data demonstrate the safety of Vip3Aa19 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 PIP was derived (See 40 CFR
158.740(b)(2)(i)). For microbial products, the need for Tier II and III
toxicity testing and residue data to verify the observed effects and
clarify the source of these effects is triggered only by significant
acute effects in studies such as the mouse oral toxicity study.
In previously submitted Vip3A studies and applications, the
designation VIP3A or Vip3A was used to describe the Vip PIP protein
and/or test material. In the final rule, it is necessary to distinguish
the various Vip3A designations based on the Crickmore Bacillus
thuringiensis Vip3A nomenclature (see https://www.lifesci.sussex.ac.uk/
Home/Neil_Crickmore/Bt). The original Vip3A toxin as expressed in
COT102 is now known as Vip3Aa19 toxin according to the Crickmore
nomenclature designation. A temporary exemption from the requirement of
tolerance already has been established for the Bacillus thuringiensis
Vip3Aa19 protein in cotton (See the Federal Register issue of July 25,
2007 (72 FR 40752) (FRL-8134-3); 40 CFR 174.501 that expires May 1,
2008.
An acute oral toxicity study was submitted for the Vip3Aa19
protein. Male and female mice (16 of each) were dosed with 3,675
milligrams/kilograms bodyweight (mg/kg bwt) of Vip3Aa19 protein. All
mice survived the study, gained weight, had no test material-related
clinical signs, and had no test material-related findings at necropsy.
This acute oral toxicity data supports the prediction that the Vip3Aa19
protein would be non-toxic to humans.
When proteins are toxic, they are known to act via acute mechanisms
and at very low dose levels (Sjoblad, Roy D., et al. 1992). Therefore,
since no effects were shown to be caused by the PIP, even at relatively
high-dose levels, the Vip3Aa19 protein is not considered toxic. Amino
acid sequence comparisons showed no similarity between the Vip3Aa19
protein and known toxic proteins available in public protein data
bases. According to the Codex Alimintarius Commission (Codex)
guidelines, the assessment of potential toxicity also includes
stability to heat (Joint Food and Agriculture Organization of the
United Nations/World Health Organization (FAO/WHO) Food Standard
Programme, Codex Alimentarius Commission, 2003\1\). A heat lability
study demonstrated that Vip3Aa19 is inactivated against fall armyworm
when heated to 55 [deg]C for 30 minutes.
---------------------------------------------------------------------------
\1\ Alinorm 03/34: Joint FAO/WHO Food Standard Programme, Codex
Alimentarius Commission, Twenty-Fifth Session, Rome, Italy 30 June-5
July, 2003. Appendix III, Guideline for the conduct of food safety
assessment of foods derived from recombinant-DNA plants and Appendix
IV, Annex on the assessment of possible allergenicity. Rome, Codex
Alimentarius Commission, 2003, p.p 47-60.
---------------------------------------------------------------------------
Since Vip3Aa19 is a protein, allergenic sensitivities were
considered. Currently, no definitive tests exist for determining the
allergenic potential of novel proteins. Therefore, EPA uses a weight-
of-the-evidence approach where the following factors are considered:
source of the trait; amino acid sequence similarity with known
allergens; prevalence in food; and biochemical properties of the
protein, including in vitro digestibility in simulated gastric fluid
(SGF), and glycosylation. This approach was described by the Codex
guidelines for the conduct of food safety assessment of food derived
from recombinant-DNA plants including the assessment of possible
allergenicity in 2003 (Joint FAO/WHO Food Standard Programme, Codex
Alimentarius Commission, 2003\1\).
Data have been submitted that demonstrate that the Vip3A from
recombinant maize (LPPACHA-0199) and E. coli (VIP3A-0100) proteins are
rapidly degraded by gastric fluid in vitro. (VIP3A-0100 refers to a
microbially expressed Vip3A that has been shown to be the equivalent of
the plant-expressed Vip3A protein.) In a solution of SGF (containing
pepsin) and either 80 microLiters ([micro]L) of LPPACHA-0199 or 320
[micro]L of VIP3A-0100 test protein, both were shown to be susceptible
to pepsin degradation. These data support the conclusion that Vip3A
proteins expressed in transgenic plants will be readily digested as a
conventional dietary protein under typical mammalian gastric
conditions. Further data demonstrate that Vip3Aa19 is not glycoslylated
and a comparison of amino acid sequences of known allergens uncovered
no evidence of any homology with Vip3Aa19, even at the level of eight
contiguous amino acid residues. These data demonstrated that mean
Vip3Aa19 concentration in cotton seed ranged from (circa). 2.51 to 3.23
micrograms ([micro]g) Vip3A/g dry weight. Vip3Aa19 was not detected in
cotton fiber or nectar. Analysis of the refined oil and de-fatted meal
by Enzyme-Linked Immunosorbent Assay (ELISA) detected Vip3Aa19 protein
in COT102 meal, but not in oil. Therefore, based on the data provided
for the specific Vip3Aa19 protein, one can conclude that the Vip3Aa19
protein is present in low levels in cotton seed and not detected in
cotton fiber.
Therefore, the potential for the Vip3Aa19 protein to be a food
allergen is minimal. As noted in Unit III., toxic proteins typically
act as acute toxins with low dose levels. Therefore, since no effects
were shown to be caused by this PIP, even at relatively high-dose
levels, the Vip3Aa19 protein is not considered toxic.
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 and to other related
substances. These considerations include dietary exposure under the
tolerance exemption and all other tolerances or exemptions in effect
for the PIP chemical residue, and exposure from non-occupational
sources. Exposure via the skin or inhalation is not likely since the
PIP is contained within plant cells, which essentially eliminates these
exposure routes or reduces these exposure routes to negligible. The
amino acid homology assessment revealed no similarities to known
aeroallergens, indicating that Vip3A has a low potential to be an
inhalation allergen. It has been demonstrated that there is no evidence
of occupationally related respiratory symptoms, based on a health
survey on migrant workers after exposure to Bacillus thuringiensis
pesticides (Berstein et al. 1999), which provides further evidence of
the negligible respiratory risks of Bacillus thuringiensis PIPs.
Exposure via residential or lawn use to infants and children is also
not expected because the use sites for the Vip3Aa19 protein are all
agricultural for control of insects. Oral exposure, at very low levels
may
[[Page 68747]]
occur from ingestion of processed corn products and, theoretically,
drinking water.
However, oral toxicity testing done at a dose in excess of 3 grams/
kilogram (gm/kg) showed no adverse effects. Furthermore, the expected
dietary exposure from cotton is several orders of magnitude lower than
the amounts of Vip3Aa19 protein shown to have no toxicity. Therefore,
even if negligible aggregate exposure should occur, the Agency
concludes that such exposure would present no harm due to the lack of
mammalian toxicity and the rapid digestibility demonstrated for the
Vip3Aa19 proteins.
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 include 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, the
Agency concludes that there are no cumulative effects arising from
Vip3Aa19 protein residues in cotton.
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 Vip3Aa19 protein include the characterization of the expressed
Vip3Aa19 protein in cotton, as well as the acute oral toxicity, heat
stability, 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 Vip3A protein
test material derived from microbial cultures (designated VIP3A-0100)
was biochemically and functionally similar to the Vip3Aa19 protein
expressed in cotton. Microbially produced protein was chosen in order
to obtain sufficient material for testing.
The acute oral toxicity data submitted supports the prediction that
the Vip3Aa19 protein would be non-toxic to humans. As mentioned in Unit
III., when proteins are toxic, they are known to act via acute
mechanisms and at very low-dose levels (Sjoblad, Roy D., et al. 1992).
Since no effects were shown to be caused by Vip3Aa19 protein, even at
relatively high dose levels (3,675 mg Vip3Aa19/kg bwt), the Vip3Aa19
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 PIP was
derived. (See 40 CFR 158.740(b)(2)(i)). Moreover, Vip3Aa19 showed no
sequence similarity to any known toxin.
Protein residue chemistry data for Vip3Aa19 were not required for a
human health effects assessment of the subject PIP ingredients because
of the lack of mammalian toxicity. Expression data demonstrated that
mean Vip3Aa19 concentrations in cotton seed ranged from approximately
2.51 to 3.23 [micro]g Vip3Aa19/g dry weight. Vip3Aa19 was not detected
in cotton fiber or nectar. Analysis of the refined oil and de-fatted
meal by ELISA detected Vip3Aa19 protein in COT102 meal, but not in oil.
Therefore, Vip3Aa19 is present in low levels in cotton seed and not
detectable in cotton fiber.
Since Vip3Aa19 is a protein, its potential allergenicity is also
considered as part of the toxicity assessment. Information considered
as part of the allergenicity assessment included data demonstrating
that the Vip3Aa19 protein came from a 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 the Vip3Aa19 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 Vip3Aa19 protein, as well as the minimal potential to
be a food allergen, demonstrate the safety of Vip3Aa19 at levels well
above possible maximum exposure levels anticipated in the crop.
The genetic material necessary for the production of the PIP active
ingredients are the nucleic acids Deoxyribonucleic acid, Ribonucleic
acid (DNA, RNA) which comprise genetic material encoding these proteins
and their regulatory regions. The genetic material DNA, RNA necessary
for the production of Vip3Aa19 protein already are exempted from the
requirement of a tolerance under a blanket exemption for all nucleic
acids (40 CFR 174.507).
B. Infants and Children Risk Conclusions
Section 408(b)(2)(C) of FFDCA 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 data base, 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
Vip3Aa19 protein and the genetic material necessary for its production
in cotton. Because there are no threshold effects of concern, the
Agency has determined that the additional tenfold margin of safety is
not necessary to protect infants and children. Further, the provisions
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 to the
U.S. population, including infants and children, from aggregate
exposure to residues of the Vip3Aa19 protein and the genetic material
necessary for its production in cotton, when it is applied or used in
accordance with good agricultural practices. 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 previously discussed, no toxicity to mammals has been
observed, nor has there been any indication of allergenicity potential
for this PIP.
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 PIP at this time.
[[Page 68748]]
B. Analytical Method(s)
A method for extraction and ELISA analysis of the Vip3Aa19 protein
in cotton has been submitted and is under review by the Agency. For the
temporary tolerance exemption, the ELISA method described with the
expression data is sufficient.
C. Codex Maximum Residue Level
No Codex maximum residue levels exist for the PIP Bacillus
thuringiensis Vip3Aa19 protein and the genetic material necessary for
its production in cotton.
VIII. Statutory and Executive Order Reviews
This final rule extends the temporary exemption from the
requirement of 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 rule has been exempted from review under
Executive Order 12866, 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) 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 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 6, 2000) do not apply to this rule. In addition, This
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).
IX. 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,
Pesticides and pests, Reporting and recordkeeping requirements.
Dated: November 27, 2007.
Janet L. Andersen,
Director, Biopesticides and Pollution Prevention Division, 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 174.501 is revised to read as follows:
Sec. 174.501 Bacillus thuringiensis Vip3Aa19 protein in cotton;
temporary exemption from the requirement of a tolerance.
Residues of Bacillus thuringiensis Vip3Aa19 protein in cotton are
temporarily exempt from the requirement of a tolerance when used as a
plant-incorporated protectant in the food and feed commodities of
cotton; vegetative-insecticidal protein in cotton, undelinted seed,
cotton, oil, cotton meal, cotton hay, cotton hulls, cotton forage, and
cotton, gin byproducts. This temporary exemption from the requirement
of tolerance will permit the use of the food commodities in this
section when treated in accordance with the provisions of the
experimental use permit 67979-EUP-7, which is being extended in
accordance with the provisions of the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA), as amended (7 U.S.C. 136). This temporary
exemption from the requirement of a tolerance expires and is revoked
May 1, 2009; however, if the experimental use permit is revoked, or if
any experience with or scientific data on this pesticide indicate that
the temporary tolerance exemption is not safe, this temporary exemption
from the requirement of a tolerance may be revoked at any time.
[FR Doc. E7-23660 Filed 12-5-07; 8:45 am]
BILLING CODE 6560-50-S
