[Federal Register Volume 68, Number 129 (Monday, July 7, 2003)]
[Rules and Regulations]
[Pages 40178-40183]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-17105]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2003-0154; FRL-7310-1]


Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 Proteins and the 
Genetic Material Necessary for their Production in Corn; Temporary 
Exemption from the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a temporary exemption from the 
requirement of a tolerance for residues of the Bacillus thuringiensis 
Cry34Ab1 and Cry35Ab1 proteins and the genetic material necessary for 
their production in corn on corn when applied/used as a plant-
incorporated protectant. Mycogen Seeds c/o Dow AgroSciences LLC, 
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. This regulation 
eliminates the need to establish a maximum permissible level for 
residues of Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins and 
the genetic material necessary for their production in corn. The 
temporary tolerance exemption will expire on April 30, 2006.

DATES: This regulation is effective July 7, 2003. Objections and 
requests for hearings, identified by docket ID number OPP-2003-0154, 
must be received by EPA on or before September 5, 2003.

ADDRESSES: Written objections and hearing requests may be submitted 
electronically, by mail, or through hand delivery/courier. Follow the 
detailed instructions as provided in Unit VIII. of the SUPPLEMENTARY 
INFORMATION.

FOR FURTHER INFORMATION CONTACT: Mike Mendelsohn, Biopesticides and 
Pollution Prevention Division (7511C), Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8715; e-mail address: [email protected].

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 categories and entities may include, but are not 
limited to:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] Pesticide manufacturing (NAICS 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 Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0154. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the Public Information and 
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The docket telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180--00.html, a 
beta site currently under development.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.

II. Background and Statutory Findings

    In the Federal Register of March 7, 2003 (68 FR 11100) (FRL-7285-
8), EPA issued a notice pursuant to section 408 of the FFDCA, 21 U.S.C. 
346a, as amended by FQPA (Public Law 104-170), announcing the filing of 
a pesticide tolerance petition (PP 0G6112) by Mycogen Seeds c/o Dow 
AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268-1054. 
This notice included a summary of the petition prepared by the 
petitioner Mycogen Seeds c/o Dow AgroSciences LLC. The docket, OPP-
2002-0350, cited in the notice contained the petition. However, the 
administrative pesticide petition number cited in the notice (PP 
0G6112) was incorrect. The correct number is PP 1G6279. There was one 
comment received in response to the notice of filing by the Center for 
Science in the Public Interest (CSPI).

Summary of Comment

    The major focus of the comments from CSPI is on the results of 
tests done to establish the sensitivity of the

[[Page 40179]]

Cry34Ab1 protein to pepsin degradation. CSPI contests the 
interpretation of the results provided by Dow AgroSciences that 
indicate the Cry34Ab1 degrades under the influence of pepsin. CSPI 
asserts that EPA cannot make a safety determination in light of these 
results and international consensus on how to address allergenicity as 
stated in the Food and Agricultural Organization/World Health 
Organization (FAO/WHO) expert consultation. Specifically, CSPI claims 
use of a less sensitive protein detection method, a pH of 1.2 instead 
of 2.0 for the pepsin buffer solution and a low concentration of the 
Cry34Ab1 protein in the assays were all utilized to achieve the 
results. CSPI suggests that all these features combine to artificially 
skew the results of the pepsin assay to show that Cry 34Ab1 is readily 
broken down by pepsin. CSPI suggests that the Cry34Ab1 protein is 
stable to gastric fluid breakdown since it is visible on Coomassie blue 
stained gels at 7 to 10 minutes of pepsin incubation. CSPI also claims 
that the initial Dow AgroScience data using a more sensitive Western 
blot assay clearly show the protein present at the 20 to 30 minute 
sample and that this endpoint is scientifically agreed upon to indicate 
resistance to pepsin degradation. CSPI recognizes that the total 
dietary exposure to the Cry34Ab1 protein likely to occur during an 
experimental use permit would not be expected to induce an allergic 
reaction and that there is still considerable scientific controversy 
around the determination of potential allergenicity of a protein new to 
the food supply. Finally, CSPI states that a test to determine 
potential allergenicity is still needed and, in the interim, acceptable 
standards for performing the currently available tests are provided by 
the FAO/WHO report on Evaluation of Allergenicity of Genetically 
Modified Foods (Rome, 2001).

EPA Response

    EPA agrees that there is still the need to develop definitive tests 
to assess potential allergenicity and that the currently employed tests 
need to follow standardized procedures. EPA also agrees that no single 
criterion of those currently utilized can alone be an indication of 
potential allergenicity. However, EPA would suggest that, while the 
guidance given by the 2001 FAO/WHO report is invaluable, there is still 
no consensus on how to implement several of the tests suggested in the 
FAO/WHO guidance nor any direction given as to critical endpoints for 
the tests suggested. This lack of consensus was confirmed by a CODEX ad 
hoc working group on allergenicity which met in Vancouver, Canada in 
September 2001, to consider the advice of the FAO/WHO expert 
consultation report from Rome 2001. This CODEX group found that, 
without development and implementation of the new tests suggested by 
FAO/WHO expert consultation, the current weight of evidence approach 
provides essentially the same information for judging allergenicity as 
that suggested by the 2001 FAO/WHO report. This advice has been 
incorporated into the latest version of the CODEX food safety 
assessment for genetically engineered foods. (CODEX, ftp://ftp.fao.org/codex/alinorm03/Al03_34e.pdf)
    The current criteria used by EPA to judge allergenicity include 
amino acid sequence similarity analyses, stability to heat, and 
enzymatic degradation. The Cry34Ab1 protein does not share significant 
amino acid similarity with known allergens either on a whole sequence 
level or on the eight amino acid stepwise comparisons, nor does the 
Cry34Ab1 protein appear to be stable to temperatures above 90 [deg]C. 
The initial data reported from the company indicated that one of the 
two proteins, Cry34Ab1, was moderately resistant to the action of 
pepsin by still being detectable on an SDS-PAGE western blot at 20-30 
minutes. EPA questioned the results found in the initial submission on 
pepsin degradation and requested more information.
    In the absence of a definitive endpoint for determining the pepsin 
resistance of a given protein, the initial results reported by Dow were 
not conclusive. The 2001 Rome FAO/WHO expert consultation report 
specifically does not mention a time endpoint for pepsin degradation of 
a protein other than the protein or a significant sized fragment being 
present at the final endpoint of 60 minutes. The literature references 
CSPI itself provided cite a range of values for pepsin stability 
ranging from 8 minutes to 2 hours and demonstrate a lack of consensus 
on pepsin resistance. EPA would therefore disagree with CSPI that there 
is a scientific consensus on visible protein bands in an SDS PAGE assay 
at 20 to 30 minutes indicating pepsin stability.
    Dow AgroScience's second submission presents results that indicate 
more rapid breakdown than the initial data. Dow AgroScience's approach 
where enzymatic degradation is expressed as a kinetic rate instead of a 
definitive substrate disappearance endpoint makes the results less 
variable since the sensitivity of the detection system does not affect 
the final result. This is because the pepsin activity can be expressed 
as a rate constant, an endpoint that is not dependent on the 
sensitivity of the detection system, is substrate concentration 
independent and is the classical method used by protein chemists to 
determine enzyme activity or in this case substrate disappearance. 
While this method may not be the final iteration of the pepsin 
degradation assay, EPA believes that an analysis that lessens assay 
variability and makes the results independent of the sensitivity of the 
detection method is an improvement.
    EPA finds that the literature references CPSI cited are 
diametrically opposed in their view of the usefulness of the pepsin 
degradation assay for prediction of allergenicity (Ref. 1). The Astwood 
et al. paper shows that, while lowering the pepsin concentration can 
lead to the appearance of fragments in an otherwise rapidly degraded 
protein, the pepsin assay is a good predictor of allergenicity (Ref. 
1). The Fu et al. paper indicates that both allergens and non-allergens 
can be stable to pepsin activity so the assay is not predictive (Ref. 
2). Both papers emphasize that protein doses, pepsin concentrations, 
and assay conditions should be equivalent when comparing proteins. 
Neither paper suggests a definitive timepoint that could be interpreted 
as indicating protein stability to pepsin. The Fu et al. paper in fact 
suggests that allergens and non-allergens can both be either resistant 
to or degraded by pepsin. The final conclusion in the Fu paper is that 
the pepsin sensitivity assay alone has no predictive value for 
allergenicity. EPA does not agree with this position but does agree 
that pepsin stability alone is not a sole criterion to be used for an 
allergenicity assessment.
    EPA agrees with CSPI that the tests used to determine potential 
allergenicity need standardization and supports efforts in that area. 
EPA believes that there is sufficient data available, considering all 
information on the Cry34Ab1 protein, to make a finding that there is a 
reasonable certainty that no harm will result from the aggregate 
exposure to the Cry34Ab1 and Cry35 Ab1 proteins as expressed in corn.
    The petition requested that 40 CFR part 180 be amended by 
establishing a temporary exemption from the requirement of a tolerance 
for residues of the plant-incorporated protectants Bacillus 
thuringiensis Cry34Ab1/Cry35Ab1 proteins and the genetic material 
necessary for their production in corn in or on corn. The Mycogen/Dow 
AgroSciences and Pioneer Hi-Bred experimental use permits associated 
with the petition are 68467-EUP-3, 68467-EUP-5, 68467-EUP-T(7), 68467-

[[Page 40180]]

EUP-I(8), 29964-EUP-1, 29964-EUP-3, 29964-EUP-U(4), and 29964-EUP-L(5)
    Section 408(c)(2)(A)(i) of the FFDCA allows EPA to establish an 
exemption from the requirement for a tolerance (the legal limit for a 
pesticide chemical residue in or on a food) only if EPA determines that 
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of the FFDCA 
defines ``safe'' to mean that ``there is a reasonable certainty that no 
harm will result from aggregate exposure to the pesticide chemical 
residue, including all anticipated dietary exposures and all other 
exposures for which there is reliable information.'' This includes 
exposure through drinking water and in residential settings, but does 
not include occupational exposure. Section 408(b)(2)(C) of the FFDCA 
requires EPA to give special consideration to exposure of infants and 
children to the pesticide chemical residue in establishing a tolerance 
and to ``ensure that there is a reasonable certainty that no harm will 
result to infants and children from aggregate exposure to the pesticide 
chemical residue. . . .'' Additionally, section 408(b)(2)(D) of the 
FFDCA requires that the Agency consider ``available information 
concerning the cumulative effects of a particular pesticide's residues 
and other substances that have a common mechanism of toxicity.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other exposures that occur as 
a result of pesticide use in residential settings.

III. Toxicological Profile

    Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed 
the available scientific data and other relevant information in support 
of this action and considered its validity, completeness and 
reliability and the relationship of this information to human risk. EPA 
has also considered available information concerning the variability of 
the sensitivities of major identifiable subgroups of consumers, 
including infants and children.
    Data have been submitted demonstrating the lack of mammalian 
toxicity at high levels of exposure to pure Cry34Ab1/Cry35Ab1 proteins. 
These data demonstrate the safety of the products at levels well above 
maximum possible exposure levels that are reasonably anticipated in the 
crops. This is similar to the Agency position regarding toxicity and 
the requirement of residue data for microbial pesticides. See 40 CFR 
158.740(b)(2)(i). For microbial products, further toxicity testing and 
residue data are triggered by significant acute effects in studies such 
as the mouse oral toxicity study, to verify the observed effects and 
clarify the source of these effects (Tiers II and III).
    The acute oral toxicity data submitted support the prediction that 
the Cry34Ab1 and Cry35Ab1 proteins would be non-toxic to humans. The 
test substance was administered to five female and five male mice 
(5,000 milligrams/kilogram (mg/kg) body weight)) in a 1:4.6 mixture of 
the two proteins, 14 kDa and 44 kDa. A single dose gavage (25 
milliliter/kilogram (mL/kg)) delivered as a 20% mixture in 0.5% 
methycellulose. All animals survived the 2-week study. One female mouse 
exhibited protruding or bulging eyes on days 6 and 7, but this resolved 
thereafter. This observation was not attributed to the treatment as it 
was an isolated observation (i.e., no other animals exhibited this). No 
other clinical signs were noted for any animals during the study. An 
initial weight loss was observed in two mice at test days 1 and 2, but 
both gained weight for the remainder of the study. All other animals 
gained weight throughout the study. No gross treatment related 
observations were recorded during the study as represented by gross 
pathologic observations. An acute oral LD50 was calculated 
for this study based upon a dosage of a 1:4.6 ratio mixture of Cry34Ab1 
(54% pure) and Cry35Ab1 (37% pure) proteins at greater than 5,000 mg/
kg, and greater than 2,000 mg/kg for an equimolar mixture (1:3) of the 
pure proteins.
    When proteins are toxic, they are known to act via acute mechanisms 
and at very low dose levels (Ref. 3). Therefore, since no acute effects 
were shown to be caused by the plant-incorporated protectants, even at 
relatively high dose levels, the Cry34Ab1 and Cry35Ab1 proteins are not 
considered toxic.
    Since Cry34Ab1 and Cry35Ab1 are proteins, allergenic sensitivities 
were considered. Current scientific knowledge suggests that common food 
allergens tend to be resistant to degradation by heat, acid, and 
proteases, may be glycosylated and present at high concentrations in 
the food. Data have been submitted that demonstrate that the Cry34Ab1 
and Cry35Ab1 proteins are rapidly degraded by gastric fluid in vitro 
and are non-glycosylated. Two in vitro digestibility studies were 
conducted to determine the lability of the Cry34Ab1 and Cry35Ab1 
proteins in an acid environment containing pepsin. In the first in 
vitro digestibility study, 1 microgram ([mu]g) of the 14 kDa protein 
(Cry34Ab1) were loaded and was visible on the SDS-PAGE gel up to the 15 
minute sample point and on the Western blot, which has greater 
sensitivity, up to the 20 minute time point. Two micrograms of the 44 
kDa protein (Cry35Ab1) was loaded on the SDS gel. A single band was 
observed on the 44 kDa SDS-PAGE at approximately 15 to 16 kDa. Western 
blot bands were observed at approximately 42 kDa and 14 kDa. These 
bands were only observed at the one minute time point, but not 
afterwards. It was concluded that both proteins are susceptible to 
degradation in the simulated gastric environment, but that the Cry35Ab1 
was more rapidly degraded. In the second in vitro digestibility study, 
the digestibility of Cry34Ab1 was further investigated and enzyme 
kinetics were used in evaluating the data. In this study, 0.36 [mu]g of 
the protein was loaded in the SDS gel. The protein appears to have 
approached full degradation by 7.5 minutes. Volumes remaining at the 10 
and 15 minute time points were excluded from the calculations since 
they were below background levels. Using this first order decay model, 
the DT50 and DT90 for this protein in the simulated gastric fluid GF 
were estimated to be 1.9 and 6.2 minutes, respectively. The Cry34Ab1 
protein is rapidly degraded in the simulated gastric fluid using this 
assay and detection methodology. The conditions of the assay are 
biologically appropriate in temperature, pH, and chemical makeup of the 
digestive solution. The first order decay rate kinetics accurately 
portray the digestion of Cry34Ab1.
    Submitted studies regarding heat stability of the Cry34Ab1 and 
Cry35Ab1 proteins demonstrate that these proteins are inactivated at 
<=90 [deg]C and <=60 [deg]C, respectively. A comparison of amino acid 
sequences of known allergens uncovered no evidence of any homology with 
Cry34Ab1 or Cry35Ab1, even at the level of 8 contiguous amino acids 
residues. The potential for the Cry34Ab1 and Cry35Ab1 proteins to be 
food allergens is minimal.
    Regarding toxicity to the immune system, the acute oral toxicity 
data submitted support the prediction that the Cry34Ab1 and Cry35Ab1 
proteins would be non-toxic to humans. When proteins are toxic, they 
are known to act via acute mechanisms and at very low dose levels (Ref. 
3). Therefore, since no effects were shown to be caused by the plant-
incorporated protectants, even at relatively high dose levels, the

[[Page 40181]]

Cry34Ab1 and Cry35Ab1 proteins are not considered toxic.

IV. Aggregate Exposures

    In examining aggregate exposure, section 408 of the FFDCA directs 
EPA to consider available information concerning exposures from the 
pesticide residue in food and all other non-occupational exposures, 
including drinking water from ground water or surface water and 
exposure through pesticide use in gardens, lawns, or buildings 
(residential and other indoor uses).

Dietary Exposure

    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. Oral exposure, at very low levels, may occur from 
ingestion of processed corn products and, potentially, drinking water. 
However a lack of mammalian toxicity and the digestibility of the 
plant-incorporated protectants have been demonstrated. The use sites 
for the Cry34Ab1 and Cry35Ab1 proteins are all agricultural for control 
of insects. Therefore, exposure via residential or lawn use to infants 
and children is not expected. Even if negligible exposure should occur, 
the Agency concludes that such exposure would present no risk due to 
the lack of toxicity demonstrated for the Cry34Ab1 and Cry35Ab1 
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 included the cumulative effects on infants and children 
of such residues and other substances with a common mechanism of 
toxicity. Because there is no indication of mammalian toxicity to these 
plant-incorporated protectants, we conclude that there are no 
cumulative effects for the Cry34Ab1 and Cry35Ab1 proteins.

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 Cry34Ab1 and Cry35Ab1 proteins include the characterization of the 
expressed Cry34Ab1 and Cry35Ab1 proteins in corn, 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 Cry34Ab1 and 
Cry35Ab1 test materials derived from microbial cultures were 
biochemically and functionally similar to the protein produced by the 
plant-incorporated protectant ingredients in corn. Production of 
microbially produced protein was chosen in order to obtain sufficient 
material for testing.
    The acute oral toxicity data submitted support the prediction that 
the Cry34Ab1 and Cry35Ab1 proteins would be non-toxic to humans. When 
proteins are toxic, they are known to act via acute mechanisms and at 
very low dose levels (Ref. 3). Since no treatment-related adverse 
effects were shown to be caused by Cry34Ab1 and Cry35Ab1 proteins, even 
at relatively high dose levels (greater than 5,000 mg/kg based upon a 
dosage of a 1:4.6 ratio mixture of (54% pure) Cry34Ab1 and (37% pure) 
Cry35Ab1 proteins and greater than 2,000 mg/kg for an equimolar mixture 
(1:3) of the pure proteins), the Cry34Ab1 and Cry35Ab1 proteins are not 
considered toxic. This is similar to the Agency position regarding 
toxicity and the requirement of residue data for the microbial Bacillus 
thuringiensis products from which this plant-incorporated protectant 
was derived. See 40 CFR 158.740(b)(2)(i). For microbial products, 
further toxicity testing and residue data are triggered by significant 
acute effects in studies such as the mouse oral toxicity study to 
verify the observed effects and clarify the source of these effects 
(Tiers II and III).
    Although Cry34Ab1 and Cry35Ab1 expression level data were 
submitted, 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. Both: (1) 
Available information concerning the dietary consumption patterns of 
consumers (and major identifiable subgroups of consumers including 
infants and children); and (2) safety factors which, in the opinion of 
experts qualified by scientific training and experience to evaluate the 
safety of food additives, are generally recognized as appropriate for 
the use of animal experimentation data were not evaluated. The lack of 
mammalian toxicity at high levels of exposure to the Cry34Ab1 and 
Cry35Ab1 proteins demonstrates the safety of the product at levels well 
above possible maximum exposure levels anticipated in the crop.
    The genetic material necessary for the production of the plant-
incorporated protectant active ingredients are the nucleic acids (DNA, 
RNA) which comprise genetic material encoding these proteins and their 
regulatory regions. The genetic material (DNA, RNA) necessary for the 
production of Cry34Ab1 and Cry35Ab1 proteins in corn have been exempted 
under the blanket exemption for all nucleic acids (40 CFR 174.175).

B. Infants and Children Risk Conclusions

    FFDCA section 408(b)(2)(C) provides that EPA shall assess the 
available information about consumption patterns among infants and 
children, special susceptibility of infants and children to pesticide 
chemical residues and the cumulative effects on infants and children of 
the residues and other substances with a common mechanism of toxicity. 
In addition, FFDCA section 408(B)(2)(C) also provides that EPA shall 
apply an additional tenfold margin of safety for infants and children 
in the case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the database unless EPA determines 
that a different margin of safety will be safe for infants and 
children.
    In this instance, based on all the available information, the 
Agency concludes that there is a finding of no toxicity for the 
Cry34Ab1 and Cry35Ab1 protein and the genetic material necessary for 
their production. Thus, there are no threshold effects of concern and, 
as a result, the provision requiring an additional margin of safety 
does not apply. Further, the 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 from 
aggregate exposure to the U.S. population, including infants and 
children, to the Cry34Ab1 and Cry35Ab1 proteins and the genetic 
material necessary for their production. This includes all anticipated 
dietary exposures and all other exposures for which there is reliable 
information. The Agency has arrived at this conclusion because, as 
discussed above, no toxicity to mammals has been observed for the 
plant-incorporated protectants.

[[Page 40182]]

VII. Other Considerations

A. Endocrine Disruptors

    The pesticidal active ingredients are proteins, 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 these plant-incorporated protectants at this time.

B. Analytical Method

    A validated method for extraction and direct enzyme linked 
immunosorbent assay analysis of Cry34Ab1 in corn grain has been 
submitted and found acceptable by the Agency.

C. Codex Maximum Residue Level

    No Codex maximum residue levels exists for the plant-incorporated 
protectants Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins and 
the genetic material necessary for their production in corn.

VIII. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. Although the procedures in those 
regulations require some modification to reflect the amendments made to 
the FFDCA by the FQPA, EPA will continue to use those procedures, with 
appropriate adjustments, until the necessary modifications can be made. 
The new section 408(g) of the FFDCA provides essentially the same 
process for persons to ``object'' to a regulation for an exemption from 
the requirement of a tolerance issued by EPA under new section 408(d), 
as was provided in the old sections 408 and 409 of the FFDCA. However, 
the period for filing objections is now 60 days, rather than 30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2003-0154 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before September 
5, 2003.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm.104, Crystal Mall 2, 1921 
Jefferson Davis Hwy., Arlington, VA. The Office of the Hearing Clerk is 
open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Office of the Hearing Clerk is 
(703) 603-0061.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VIII.A., 
you should also send a copy of your request to the PIRIB for its 
inclusion in the official record that is described in Unit I.B.1. Mail 
your copies, identified by docket ID number OPP-2003-0154, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in Unit I.B.1. You may also send an electronic copy of 
your request via e-mail to: [email protected]. Please use an ASCII 
file format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. 
Do not include any CBI in your electronic copy. You may also submit an 
electronic copy of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

IX. References

    1. Astwood J.D., Leach, J.N. and Fuch, R.L. (1996) ``Stability of 
Food Allergens to Digestion In Vitro.'' Nature Biotech. 14:1269-1273.
    2. Fu, T-J, Abbott, U.R., Hatzos, C. (2002) ``Digestibility of Food 
Allergens and Nonallergenic Proteins in Simulated Gastric Fluid and 
Simulated Intestinal Fluid - A Comparative Study.'' J. Agric. Food 
Chem. 50:7154-7160.
    3. Sjoblad, Roy D., et al. (1992) ``Toxicological Considerations 
for Protein Components of Biological Pesticide Products.'' Regulatory 
Toxicology and Pharmacology 15L, 3-9.

[[Page 40183]]

X. Statutory and Executive Order Reviews

    This final rule establishes an exemption from the tolerance 
requirement under section 408(d) of the FFDCA in response to a petition 
submitted to the Agency. The Office of Management and Budget (OMB) has 
exempted these types of actions from review under Executive Order 
12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 
1993). Because this rule has been exempted from review under Executive 
Order 12866 due to its lack of significance, this rule is not subject 
to Executive Order 13211, Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, 
May 22, 2001). This final rule does not contain any information 
collections subject to OMB approval under the Paperwork Reduction Act 
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or 
contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor 
does it require any special considerations under Executive Order 12898, 
entitled Federal Actions to Address Environmental Justice in Minority 
Populations and Low-Income Populations (59 FR 7629, February 16, 1994); 
or OMB review or any Agency action under Executive Order 13045, 
entitled Protection of Children from Environmental Health Risks and 
Safety Risks (62 FR 19885, April 23, 1997). This action does not 
involve any technical standards that would require Agency consideration 
of voluntary consensus standards pursuant to section 12(d) of the 
National Technology Transfer and Advancement Act of 1995 (NTTAA), 
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of the FFDCA, such as the exemption in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled Federalism 
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive Order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency 
has determined that this rule does not have any ``tribal implications'' 
as described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
Order to include regulations that have ``substantial direct effects on 
one or more Indian tribes, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.'' 
This rule will not have substantial direct effects on tribal 
governments, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal government and Indian tribes, as specified in 
Executive Order 13175. Thus, Executive Order 13175 does not apply to 
this rule.

XI. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
to each House of the Congress and to the Comptroller General of the 
United States. EPA will submit a report containing this rule and other 
required information to the U.S. Senate, the U.S. House of 
Representatives, and the Comptroller General of the United States prior 
to publication of this final rule in the Federal Register. This final 
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: June 23, 2003.
James Jones,
Director, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

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

0
2. Section 180.1242 is added to subpart D to read as follows:


Sec.  180.1242  Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins 
and the genetic material necessary for their production in corn; 
temporary exemption from the requirement of a tolerance.

    Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins and the 
genetic material necessary for their production in corn are temporarily 
exempted from the requirement of a tolerance when used as plant-
incorporated protectants in the food and feed commodities of field 
corn, sweet corn and popcorn. This temporary exemption from the 
requirement of a tolerance will permit the use of the food commodities 
in this paragraph when treated in accordance with the provisions of the 
experimental use permits 68467-EUP-3, 68467-EUP-5, 68467-EUP-T(7), 
68467-EUP-I(8), 29964-EUP-1, 29964-EUP-3, 29964-EUP-U(4), and 29964-
EUP-L(5) which may be issued and amended/extended under 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 April 30, 2006. This temporary 
exemption from the requirement of a tolerance may be revoked at any 
time if the experimental use permit is revoked or if any experience 
with or scientific data on this pesticide indicate that the tolerance 
is not safe.

[FR Doc. 03-17105 Filed 7-3-03; 8:45 am]
BILLING CODE 6560-50-S