Document ID: EPA-HQ-OPP-2007-0830-0004
Agency: epa
Document Type: Rule
Title: Bacillus thuringiensis Vip3Aa Proteins in Corn and Cotton; Exemption from the Requirement of a Tolerance
Posted Date: 2008-08-06T04:00Z

[Federal Register: August 6, 2008 (Volume 73, Number 152)]
[Rules and Regulations]               
[Page 45620-45624]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06au08-13]                         

=======================================================================
-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[EPA-HQ-OPP-2007-0830; FRL-8374-2]

 
Bacillus thuringiensis Vip3Aa Proteins in Corn and Cotton; 
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 Vip3Aa 
proteins in or on the food and feed commodities of corn; corn, field; 
corn, sweet; corn, pop; and cotton; cotton, undelinted seed; cotton, 
refined oil; cotton, meal; cotton, hay; cotton, hulls; cotton, forage; 
and cotton, gin byproducts, when used as plant-incorporated protectants 
in those food and feed commodities. 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 Vip3Aa proteins in or on corn; 
corn, field; corn, sweet; corn, pop; and cotton, undelinted seed; 
cotton, refined oil; cotton, meal; cotton, hay; cotton, hulls; cotton, 
forage; and cotton, gin byproducts, when applied or used as plant-
incorporated protectants.

DATES: This regulation is effective August 6, 2008. Objections and 
requests for hearings must be received on or before October 6, 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-2007-0830. To access the 
electronic docket, go to http://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 http://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 
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 http://
www.regulations.gov, you may access this ``Federal Register'' document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr. You may also access a 
frequently updated electronic version of 40 CFR part 180 through the 
Government Printing Office's pilot e-CFR site at http://
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-2007-0830 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 October 6, 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-2007-0830, by one of the following methods.
     Federal eRulemaking Portal: http://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

[[Page 45621]]

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 November 2, 2007 (72 FR 62237) (FRL-
8153-8), 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 7F7254) by Syngenta Seeds, Inc., P.O. Box 12257, 3054 E. 
Cornwallis Road, Research Triangle Park, NC 27709. The petition 
requested that 40 CFR part 180 be amended by establishing an exemption 
from the requirement of a tolerance for residues of Bacillus 
thuringiensis Vip3Aa proteins in or on all food commodities when 
applied or used as plant-incorporated protectants. This notice included 
a summary of the petition prepared by the petitioner Syngenta Seeds, 
Inc. One comment was received in response to the notice of filing. The 
commenter objected to the petition and expressed concerns about EPA's 
regulation of human exposure to toxic chemicals. The Agency understands 
the commenter's concerns regarding toxic substances and the potential 
effects to humans. Pursuant to its authority under the FFDCA, and as 
discussed further in this Unit, EPA conducted a comprehensive 
assessment of representative Vip3Aa proteins, including a review of 
acute oral toxicity data on several Vip3Aa proteins, amino acid 
sequence comparisons to known toxins and allergens, as well as data 
demonstrating that the representative Vip3Aa proteins are rapidly 
degraded by gastric fluid in vitro, are not glycosylated, and are 
present in low levels in the tissues of the corn and cotton plants 
containing these plant-incorporated protectants. Based on these data, 
the Agency has concluded that there is a reasonable certainty that no 
harm will result from dietary exposure to residues of these proteins in 
or on the food and feed commodities corn; corn, field; corn, sweet; 
corn, pop; and cotton, undelinted seed; cotton, refined oil; cotton, 
meal; cotton, hay; cotton, hulls; cotton, forage; and cotton, gin 
byproducts, when used as plant-incorporated protectants in those food 
and feed commodities. 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 corn; corn, field; corn, sweet; corn, pop; and 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 
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 Vip3Aa19 and 
Vip3Aa20 proteins. These data demonstrate the safety of these 
particular Vip3Aa proteins at levels well above the maximum possible 
exposure levels that are reasonably anticipated in cotton (Vip3Aa19) 
and corn (Vip3Aa20). 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 these plant-incorporated protectants were derived (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 mouse oral toxicity study, to verify the 
observed adverse effects and clarify the source of these effects.
    Syngenta submitted four acute oral toxicity studies conducted on 
mice. Three of the studies were conducted with microbially-produced 
Vip3Aa proteins (Vip3Aa1, Vip3Aa19, and Vip3Aa20) with slight 
variations in amino acid sequence (1-2 amino acid differences), and one 
study was conducted with transgenic corn leaf tissue expressing 
Vip3Aa19 as the test material. No treatment-related adverse effects 
were observed in any of the studies. The results of these studies 
showed that the oral LD50 for mice (males, females, and 
combined) was greater than 3,675 milligrams/kilogram/body weight (mg/
kg/bwt) (the highest dose tested) for the tested Vip3Aa proteins.
    When proteins are toxic, they are known to act via acute mechanisms 
and at very low dose levels (Sjoblad, Roy D., et al., ``Toxicological 
Considerations for Protein Components of Biological Pesticide 
Products,'' Regulatory Toxicology and Pharmacology 15, pages 3-9 
(1992)). Therefore, since no acute effects were shown to be caused by 
the Vip3Aa19 and Vip3Aa20 proteins, even at relatively high dose 
levels, they are not considered toxic. (This is also true

[[Page 45622]]

of the Vip3Aa1 protein that was tested.) Further, amino acid sequence 
comparisons showed no similarities between Vip3Aa19 and Vip3Aa20, on 
the one hand, and known toxic proteins in protein databases, on the 
other hand, that would raise a safety concern.
    Since Vip3Aa 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 Vip3Aa follows:
     Source of the trait. Bacillus thuringiensis, the 
microorganism from which Vip3Aa proteins are derived, is not considered 
to be a source of allergenic proteins.
     Amino acid sequence. A comparison of the amino acid 
sequence of Vip3Aa19 and Vip3Aa20 with known allergens showed no 
significant sequence identity over 80 amino acids or identity at the 
level of eight contiguous amino acid residues.
     Digestibility. Both Vip3Aa19 and Vip3Aa20 proteins are 
digested rapidly in simulated gastric fluid containing pepsin.
     Glycosylation. Both Vip3Aa19 and Vip3Aa20 were shown not 
to be glycosylated.
    Considering all of the available information on Vip3Aa19 and 
Vip3Aa20, EPA concludes that the potential for these specific proteins 
to be food allergens is minimal. Moreover, as further explained below 
(and in section VI.a. of this final rule), EPA believes these data and 
the other submitted data demonstrating a lack of mammalian toxicity at 
high levels of exposure to Vip3Aa19 and Vip3Aa20 can be extrapolated to 
cover Vip3Aa more generally.
    Vip3Aa is the designation assigned to a closely-related group of 
similar insecticidal proteins isolated from Bacillus thuringiensis. The 
specific variants referred to throughout this document (i.e., Vip3Aa19 
and Vip3Aa20) are isolates of Vip3Aa protein. All Vip3Aa proteins 
(there are 25 known Vip3Aa proteins and there are sequences available 
for 19 of these) are highly related. Indeed, the amino acid sequence of 
all the Vip3Aa proteins can only vary up to 5% to be considered a part 
of the Vip3Aa group. With respect to the 19 Vip3Aa proteins for which 
sequences are available, they vary by less than 28 amino acids out of 
the 789 amino acids that make up the protein. This level of sequence 
similarity makes that group of 19 Vip3Aa protein variants 96% identical 
overall. The sequence identity between any two individual sequences is 
even higher. For example, the sequences of the protein variants tested 
by Syngenta (i.e., Vip3Aa19 and Vip3Aa20) are over 99.7% identical. 
Finally, as to the few amino acid differences that do exist between the 
Vip3Aa variants, these differences do not alter the surrounding 
sequence, rarely occur as contiguous amino acids, and are often 
substitutions with similar chemical side groups indicating similar 
chemical functionality. Therefore, EPA finds that none of the Vip3Aa 
variants would be expected to have significant amino acid sequence 
identity -- which is defined as either 35% identity over an 80 amino 
acid stretch and, for allergens, at the level of eight contiguous amino 
acids -- with a toxin, an anti-nutrient or an allergen.
    This conclusion is further supported by EPA's overall safety 
assessment that includes other considerations such as the source of the 
trait, digestibility and glycosylation. As noted in this Unit, Bacillus 
thuringiensis (from which the Vip3Aa proteins are derived) is not 
considered to be a source of allergenic proteins. Furthermore, since 
all the Vip3Aa proteins have extremely homogenous structural 
similarities (as explained in this Unit), they are highly likely to 
show similar biochemical characteristics in terms of digestibility and 
glycosylation. So, as is the case for both Vip3Aa19 and Vip3Aa20, EPA 
expects that all Vip3Aa proteins will be rapidly digested under 
simulated gastric conditions and will not be glycosylated. Finally, it 
is also highly relevant here that microbial pesticide products, which 
are distinct from plant-incorporated protectant pesticide products, 
containing Bacillus thuringiensis and its components (which could 
include microbially-expressed Vip3Aa proteins) are already exempt from 
the requirement for a tolerance under 40 CFR 180.1011.
    Accordingly, EPA believes that the foregoing supports EPA's 
reasonable certainty of no harm finding not only for the Vip3Aa19 and 
Vip3Aa20 protein variants, but also for all other closely-related 
members of the Vip3Aa designation as described using the Crickmore 
classification system (Crickmore, N., Zeigler, D.R., Schnepf, E., Van 
Rie, J., Lereclus, D., Baum, J, Bravo, A. and Dean, D.H. ``Bacillus 
thuringiensis toxin Nomenclature'' (2007) http://
www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/).

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 Vip3Aa 
proteins) and to other related substances. These considerations include 
dietary exposure under the tolerance exemption and all other tolerances 
or exemptions in effect for the plant-incorporated protectant's 
chemical residue, and exposure from non-occupational sources. Exposure 
via the skin or inhalation is not likely since the plant-incorporated 
protectant is contained within plant cells, which essentially 
eliminates these exposure routes or reduces these exposure routes to 
negligible. In addition, even if exposure can occur through inhalation, 
the potential for Vip3Aa to be an allergen is low, as discussed in this 
Unit. Although the allergenicity assessment focuses on potential to be 
a food allergen, the data also indicate a low potential for Vip3Aa to 
be an inhalation allergen. Exposure via residential or lawn use to 
infants and children is also not expected because the use sites for 
Vip3Aa proteins are agricultural. Oral exposure, at very low levels, 
may occur from ingestion of food commodities containing Vip3Aa protein 
residues and, theoretically, drinking water. However oral toxicity 
testing (as discussed above) 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 residues of 
representative Vip3Aa proteins 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

[[Page 45623]]

indication of mammalian toxicity resulting from exposure to Vip3Aa 
proteins, we conclude that there are no cumulative effects for the 
Vip3Aa proteins.

VI. Determination of Safety for U.S. Population, Infants and Children

    1. Toxicity and allergenicity conclusions. The data submitted and 
cited regarding potential health effects for Vip3Aa proteins includes 
the characterization of representative Vip3Aa proteins, as well as the 
acute oral toxicity studies, amino acid sequence comparisons to known 
allergens and toxins, and in vitro digestibility of the representative 
Vip3Aa proteins. The results of these studies were used to evaluate 
humansk, and the validity, completeness, and reliability of the 
available data from the studies were also considered.
    Adequate information was submitted to show that the Vip3Aa test 
materials derived from microbial cultures were biochemically and 
functionally equivalent to the proteins produced by the plant-
incorporated protectant ingredient in the plants. Microbially produced 
proteins were used in the studies so that sufficient material for 
testing was available.
    The acute oral toxicity data submitted for the representative 
Vip3Aa proteins support the prediction that Vip3Aa proteins will be 
non-toxic to humans. As mentioned above, when proteins are toxic, they 
are known to act via acute mechanisms and at very low dose levels 
(Sjoblad, Roy D., et al., ``Toxicological Considerations for Protein 
Components of Biological Pesticide Products,'' Regulatory Toxicology 
and Pharmacology 15, pages 3-9 (1992)). Since no treatment-related 
adverse effects were shown to be caused by the representative Vip3Aa 
proteins, even at relatively high dose levels, Vip3Aa proteins are not 
considered toxic. Basing this conclusion on acute oral toxicity data 
without requiring further toxicity testing or 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 (Tiers II 
and III) 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 representative Vip3Aa proteins in corn 
and cotton tissues.
    Since Vip3Aa are proteins, potential allergenicity is also 
considered as part of the toxicity assessment. Considering all of the 
available information, including that:
     Vip3Aa originates from a non-allergenic source.
     Vip3Aa19 and Vip3Aa20 have no sequence similarities with 
known allergens.
     Vip3Aa19 and Vip3Aa20 are not glycosylated.
     Vip3Aa19 and Vip3Aa20 are rapidly digested in simulated 
gastric fluid.
     The data developed for Vip3Aa19 and Vip3Aa20 can be 
extrapolated to all Vip3Aa proteins due to the extremely high level of 
structural similarity that exists between and among Vip3Aa proteins, 
EPA has concluded that the potential for Vip3Aa 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 representative Vip3Aa proteins, as well as the minimal 
potential to be a food allergen, demonstrate the safety of Vip3Aa 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 deoxyribo nucleic 
acids/ribonucleic acid (DNA/RNA) that encode these proteins and 
regulatory regions. The genetic material DNA/RNA necessary for the 
production of Vip3Aa proteins has been exempted from the requirement of 
a tolerance under 40 CFR 174.507 (Nucleic acids that are part of a 
plant-incorporated protectant; exemption from the requirement of a 
tolerance).
    2. 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 Vip3Aa 
proteins. Thus, there are no threshold effects of concern and, as a 
result, the provision requiring an additional tenfold margin of safety 
does not apply. Further, the considerations of consumption patterns, 
special susceptibility, and cumulative effects do not apply.
    3. 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 Vip3Aa proteins. 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 Vip3Aa proteins.

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 the 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 Vip3Aa in cotton as well 
as a qualitative ELISA method for detecting Vip3Aa in corn.

C. Codex Maximum Residue Level

    No Codex maximum residue level exists for the plant-incorporated 
protectant Bacillus thuringiensis Vip3Aa proteins and the genetic 
material necessary for their production in corn and cotton.

VIII. 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

[[Page 45624]]

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).

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, 
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: 21 U.S.C. 321(q), 346a and 371.

0
2. Section 174.501 in subpart D is revised to read as follows:

Sec.  174.501  Bacillus thuringiensis Vip3Aa protein in corn and 
cotton; exemption from the requirement of a tolerance.

    Residues of Bacillus thuringiensis Vip3Aa proteins in or on corn or 
cotton are exempt from the requirement of a tolerance when used as 
plant-incorporated protectants in or on the food and feed commodities 
of corn; corn, field; corn, sweet; corn, pop; and cotton; cotton, 
undelinted seed; cotton, refined oil; cotton, meal; cotton, hay; 
cotton, hulls; cotton, forage; and cotton, gin byproducts.

Sec.  174.528  [Removed]

0
3. Section 174.528 is removed from Subpart D.
[FR Doc. E8-17931 Filed 8-5-08; 8:45 am]

BILLING CODE 6560-50-S