[Federal Register Volume 70, Number 182 (Wednesday, September 21, 2005)]
[Rules and Regulations]
[Pages 55254-55260]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-18582]


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

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[OPP-2005-0211; FRL-7735-4]


Bacillus Thuringiensis Cry34Ab1 and Cry35Ab1 Proteins and the 
Genetic Material Necessary for Their Production in Corn; 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 Cry34Ab1 and 
Cry35Ab1 proteins and the genetic material necessary for their 
production in corn on corn, field; corn, sweet; and corn, pop 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 an exemption from the 
requirement of a tolerance. This regulation eliminates the

[[Page 55255]]

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.

DATES: This regulation is effective September 21, 2005. Objections and 
requests for hearings must be received on or before November 21, 2005.

ADDRESSES: To submit a written objection or hearing request follow the 
detailed instructions as provided in Unit VIII. of the SUPPLEMENTARY 
INFORMATION. EPA has established a docket for this action under Docket 
identification (ID) number OPP-2005-0211. All documents in the docket 
are listed in the EDOCKET index at http://www.epa.gov/edocket. Although 
listed in the index, some information is not publicly available, i.e., 
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 either electronically 
in EDOCKET or in hard copy at the Public Information and Records 
Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1801 S. 
Bell St., 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.

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 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. To determine 
whether you or your business may be affected by this action, you should 
carefully examine the applicability provisions in Unit I. 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 and Other 
Related Information?

    In addition to using EDOCKET (http://www.epa.gov/edocket/), 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 174 
is available at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/.

II. Background and Statutory Findings

    In the Federal Register of August 31, 2004 (69 FR 53060) (FRL-7369-
7), EPA issued a notice pursuant to section 408(d)(3) of the FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance 
petition (PP 3F6785) by Mycogen Seeds c/o Dow AgroSciences LLC, 9330 
Zionsville Road, Indianapolis, IN 46268. The petition requested that a 
temporary exemption from the requirement of a tolerance be established 
for residues of Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins 
and the genetic material necessary for their production in corn. This 
notice included a summary of the petition prepared by the petitioner 
Mycogen Seeds c/o Dow AgroSciences LLC. One comment was received from a 
private citizen who opposed issuance of a final rule. She expressed 
concern regarding Dow's record, genetically modified corn, the impact 
that killing rootworm would have on the environment, and that the 
notice of filing mentioned ``studies'' without giving a specific 
number. The Agency understands and recognizes that some individuals 
believe that genetically modified crops and food should be banned 
completely. Corn rootworms are a significant agricultural pest and are 
extensively treated in the United States. Pursuant to its authority 
under the Federal Food, Drug, and Cosmetic Act (FFDCA), EPA has 
conducted a comprehensive assessment of the Cry34Ab1 and Cry35Ab1 
proteins and the genetic material necessary for their production in 
corn. EPA has concluded that there is a reasonable certainty that no 
harm will result from dietary exposure to these proteins as expressed 
in genetically modified corn. Specific studies were listed in the 
administrative material provided in the docket.
    Section 408(c)(2)(A)(i) of the FFDCA allows EPA to establish an 
exemption from the requirement for a tolerance (the legal limit for a 
pesticide chemical residue in or on a food) only if EPA determines that 
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of the FFDCA 
defines ``safe'' to mean that ``there is a reasonable certainty that no 
harm will result from aggregate exposure to the pesticide chemical 
residue, including all anticipated dietary exposures and all other 
exposures for which there is reliable information.'' This includes 
exposure through drinking water and in residential settings, but does 
not include occupational exposure. Pursuant to section 408(c)(2)(B), in 
establishing or maintaining in effect an exemption from the requirement 
of a tolerance, EPA must take into account the factors set forth in 
section 408(b)(2)(C), which require EPA to give special consideration 
to exposure of infants and children to the pesticide chemical residue 
in establishing a tolerance and to ``ensure that there is a reasonable 
certainty that no harm will result to infants and children from 
aggregate exposure to the pesticide chemical residue....'' 
Additionally, section 408(b)(2)(D) of the FFDCA requires that the 
Agency consider ``available information concerning the cumulative 
effects of a particular pesticide's residues'' and ``other substances 
that have a common mechanism of toxicity.``
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other exposures that occur as 
a result of pesticide use in residential settings.

III. Toxicological Profile

    Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed 
the available scientific data and other relevant information in support 
of this action and considered its validity, completeness, and 
reliability and the relationship of this information to human risk. EPA 
has also considered available information concerning the variability of 
the sensitivities of major identifiable subgroups of consumers, 
including infants and children.

[[Page 55256]]

    Acute oral toxicity data have been submitted demonstrating the lack 
of mammalian toxicity at high levels of exposure to the pure Cry34Ab1 
and Cry35Ab1 proteins separately and combined. These data demonstrate 
the safety of the products at levels well above maximum possible 
exposure levels that are reasonably anticipated in the crops. Basing 
this conclusion on acute oral toxicity data without requiring further 
toxicity testing and residue data is similar to the Agency position 
regarding toxicity and the requirement of residue data for the 
microbial Bacillus thuringiensis products from which these plant-
incorporated protectants were 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).
    Three acute oral toxicity studies on Cry34Ab1 and Cry35Ab1 in mice 
were submitted, which indicated that these proteins are non-toxic to 
humans.
    In an oral toxicity study of Cry34Ab1 alone, Cry34Ab1 produced from 
microbial culture was administered to five male mice (5,000 milligrams/
kilogram (mg/kg) body weight) by oral gavage as a 20% mixture in a 0.5% 
aqueous methylcellulose vehicle. All animals survived the 2-week study. 
No clinical signs were noted for any animals during the study. An 
initial weight loss was observed in three mice at test days 1 and 2, 
but they gained weight for the remainder of the study. The two other 
animals gained weight throughout the study. No treatment-related gross 
pathologic changes were observed during the study. Under the conditions 
of this study, the acute oral LD50 for the test substance in 
male CD-1 mice is greater than 5,000 mg/kg. Since the test substance 
contained Cry34Ab1 at 54% purity, the acute oral LD50 for 
the pure Cry34Ab1 protein is greater than 2,700 mg/kg.
    In an oral toxicity study of Cry35Ab1 alone, Cry35Ab1 produced from 
microbial culture was administered to five male mice (5,000 mg/kg body 
weight) by oral gavage as a 20% mixture in a 0.5% aqueous 
methylcellulose vehicle. All animals survived the 2-week study. No 
clinical signs were noted for any animal during the study. An initial 
weight loss was observed in two mice at test days 1 and 2, but they 
gained weight for the remainder of the study. One animal had 
fluctuating body weight. The other two animals gained weight throughout 
the study. No treatment-related gross pathologic changes were observed 
during the study. Under the conditions of this study, the acute oral 
LD50 for the test substance in male CD-1 mice is greater 
than 5,000 mg/kg. Since the test substance contained Cry35Ab1 at 37% 
purity, the acute oral LD50 for the pure Cry35Ab1 protein is 
greater than 1,850 mg/kg.
    Finally, in an oral toxicity of Cry34Ab1 and Cry35Ab1 combined, a 
mixture of the microbially produced Cry34Ab1 and Cry35Ab1 proteins 
(5,000 mg test material, containing 482 mg pure Cry34Ab1 and 1,520 mg 
pure Cry35Ab1 (corresponding to an equimolar ratio), per kg body 
weight) was administered by oral gavage to five female and five male 
mice as a 20% mixture in 0.5% aqueous methylcellulose. 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 treatment related gross pathologic changes 
were noted. Under the conditions of the study, the acute oral 
LD50 of the test material in male and female CD-1 mice is 
greater than 5,000 mg/kg body weight, corresponding to 2,000 mg/kg of 
an equimolar ratio of the pure 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, 3-9 (1992)). 
Therefore, since no 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. Further, amino 
acid sequence comparisons showed no similarity between the Cry34Ab1 and 
Cry35Ab1 proteins to known toxic proteins available in public protein 
data bases.
    Since Cry34Ab1 and Cry35Ab1 are proteins, allergenic potential was 
also considered. Currently, no definitive tests for determining the 
allergenic potential of novel proteins exist. 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. Current scientific knowledge suggests that 
common food allergens tend to be resistant to degradation by acid and 
proteases; may be glycosylated, and can be present at high 
concentrations in the food. In the past, EPA has also considered heat 
stability in assessing allergenicity potential; however, the FIFRA 
Scientific Advisory Panel at a March 1-2, 2005 meeting stated that heat 
stability based on a bioactivity assay is of minimal to no value in 
predicting the allergenicity potential of novel proteins, and EPA 
agrees. Therefore, EPA did not consider heat stability of these 
proteins in its weight-of-evidence approach.
    1. Source of the trait. Bacillus thuringiensis is not considered to 
be a source of allergenic proteins.
    2. Amino acid sequence. A comparison of amino acid sequences of 
Cry34Ab1 and Cry35Ab1 with known allergens showed no overall sequence 
similarities or homology at the level of eight contiguous amino acid 
residues.
    3. Prevalence in food. Expression level analysis indicated that the 
proteins are present at relatively low levels in corn; on a dry weight 
basis, Cry34Ab1 is present at a concentration of approximately 50 
nanograms/milligram (ng/mg) in grain from Event 59122-7, and Cry35Ab1 
is present at a concentration of approximately 1 ng/mg in grain from 
Event 59122-7. Thus, expression of the Cry34Ab1 and Cry35Ab1 proteins 
in corn kernels has been shown to be in the parts per million range.
    4. Digestibility. Two in vitro digestibility studies were conducted 
to determine the stability of the Cry34Ab1 and Cry35Ab1 proteins in 
simulated gastric fluid (i.e., an acid environment containing pepsin; 
SGF). In the first in vitro digestibility study, the proteins were 
incubated in SGF (pepsin concentration: 3.2 milligrams/milliliter (mg/
mL); pH 1.2; 37[deg] C) with a pepsin to protein substrate ratio of 
approximately 20:1, molecule/molecule (mol/mol) (equivalent to 60:1, w/
w for Cry34Ab1 and 17:1, w/w for Cry35Ab1). Samples taken at 1, 5, 7, 
15, 20, 30, and 60 minutes were analyzed by sodium dodecyl sulfate 
polyacrylamide gel electrophoresis (SDS-PAGE) and western blot. 
Cry35Ab1 was no longer visible at the 5-minute time-point using both 
SDS-PAGE stained with Coomassie Brilliant Blue and western blot 
detection. Cry34Ab1 was visible on the stained gel for the 15-minute 
sample,

[[Page 55257]]

but not in later sample time points. In the western blot analysis, 
Cry34Ab1 was visible in the 20-minute sample, but not in later sample 
time points. In conclusion, this first study showed that Cry34Ab1 was 
digested within 30 minutes and Cry35Ab1 was digested within 5 minutes 
in SGF under the conditions of the study.
    Because Cry34Ab1 appeared to be somewhat resistant to SGF in the 
study described above that used the time-to-disappearance endpoint, Dow 
submitted a second study on the in vitro digestibility of Cry34Ab1 in 
SGF using a kinetic approach. The digestion was performed under the 
same conditions as the previous study except that reaction mixtures 
were shaken during incubation, and samples were analyzed at 1, 2, 3, 5, 
7.5, 10, 15, and 20 minutes. The previous study on pepsin digestibility 
of Cry34Ab1 and Cry35Ab1, as well as other pepsin digestibility studies 
used in allergenicity assessments, focused on the time required for the 
protein to become undetectable, and therefore, the results are 
dependent on the detection limit of the analytical method used. In this 
second study, Dow determined the rate of pepsin digestion of Cry34Ab1 
by measuring the relative amounts of Cry34Ab1 at each of the time 
points based on SDS-PAGE densitometry estimates. Under the conditions 
of the study, the rate of decay fit a first-order model (with respect 
to Cry34Ab1 concentration), and Dow estimated the DT50 
(half-life) and DT90 (time until 90% decay) to be 1.9 
minutes and 6.2 minutes, respectively. In this experiment, Cry34Ab1 was 
visible on gels and blots in 15-minute time point samples but not in 
20-minute time point samples.
    Because the digestibility of Cry34Ab1 was assessed using a 
different method (i.e., the kinetic approach) rather than the typical 
end-point method that has been used previously, comparison studies 
using the kinetic approach to assess the digestibility of known 
allergens and non-allergens were submitted to validate the method and 
allow comparison of the digestibility of Cry34Ab1 with known allergens 
and non-allergens. In the comparison study where the conditions used 
were the same as those used in the kinetic study on the digestibility 
of Cry34Ab1, two allergens and two non-allergens were shown to digest 
similarly to Cry34Ab1. From these studies and published studies, EPA 
concludes that Cry35Ab1 is rapidly digested and Cry34Ab1 is digested at 
a moderate rate in SGF; Cry34Ab1 appears to digest slower than 
previously registered proteins and many other proteins that are not 
considered allergens but faster than most previously tested allergens.
    On March 1-2, 2005, EPA held a FIFRA Scientific Advisory Panel 
(SAP) meeting, http://www.epa.gov/oscpmont/sap/#march, to address the 
scientific issues that arose during the human health safety assessment 
of Cry34Ab1 and Cry35Ab1. EPA asked the SAP to comment on EPA's 
allergenicity assessment of Cry34Ab1. The SAP agreed with EPA's 
preliminary assessment that the allergenicity potential of Cry34Ab1 is 
low. However, the Panel based its conclusion in part on statements made 
by Dow that Cry34Ab1 and Cry35Ab1 do not aggregate in solution. The 
Panel was concerned that if the proteins were to aggregate, protease 
binding sites could be masked, and the rate of digestion could be 
slower than was observed for the individual proteins. Therefore, EPA 
asked Dow to submit data supporting the claim that Cry34Ab1 and 
Cry35Ab1 do not associate with one another in solution.
    To support the digestibility studies on the individual proteins, 
Dow submitted a study using size exclusion chromatography, which 
demonstrated that Cry34Ab1 and Cry35Ab1 do not associate with one 
another in solution under acidic conditions.
    5. Glycosylation. Cry34Ab1 and Cry35Ab1 expressed in corn were 
shown not to be glycosylated.
    6. Conclusion. Considering all of the available information: (1) 
Cry34Ab1 and Cry35Ab1 originate from a non-allergenic source;(2) 
Cry34Ab1 and Cry35Ab1 have no overall sequence similarities or homology 
at the level of eight contiguous amino acid residues with known 
allergens; (3) Cry34Ab1 and Cry35Ab1 will only be present at low levels 
in food; (4) Cry35Ab1 is rapidly digested in SGF, and Cry34Ab1 is 
digested at a moderate rate in SGF; and (5) Cry34Ab1 and Cry35Ab1 are 
not glycoslyated when expressed in maize. EPA has concluded that the 
potential for the Cry34Ab1 and Cry35Ab1 proteins to be food allergens 
is minimal. The FIFRA SAP that met on March 1-2, 2005, agreed with this 
conclusion regarding the allergenicity potential of Cry34Ab1. There 
were no triggers to raise concern about the allergenicity of Cry35Ab1, 
so the SAP was not asked to comment specifically on Cry35Ab1. As noted 
above, toxic proteins typically act as acute toxins with low dose 
levels. Therefore, since no effects were shown to be caused by the 
plant-incorporated protectants, even at relatively high dose levels, 
the 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).
    The Agency has considered available information on the aggregate 
exposure levels of consumers (and major identifiable subgroups of 
consumers) to the pesticide chemical residue and to other related 
substances. These considerations include dietary exposure under the 
tolerance exemption and all other tolerances or exemptions in effect 
for the plant-incorporated protectants chemical residue, and exposure 
from non-occupational sources. Exposure via the skin or inhalation is 
not likely since the plant-incorporated protectants are contained 
within plant cells, which essentially eliminates these exposure routes 
or reduces these exposure routes to negligible. Exposure via 
residential or lawn use to infants and children is also not expected 
because the use sites for the Cry34Ab1 and Cry35Ab1 proteins are all 
agricultural for control of insects. Oral exposure, at very low levels, 
may occur from ingestion of processed corn products and, potentially, 
drinking water. However, oral toxicity testing showed no adverse 
effects. Furthermore, the expression of the Cry34Ab1 and Cry35Ab1 
proteins in corn kernels has been shown to be in the parts per million 
range, which makes the expected dietary exposure several orders of 
magnitude lower than the amounts of Cry34Ab1 and Cry35Ab1 proteins 
shown to have no toxicity. Therefore, even if negligible aggregate 
exposure should occur, the Agency concludes that such exposure would 
result in no harm due to the lack of mammalian toxicity and low 
potential for allergenicity 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, 
resulting from the

[[Page 55258]]

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, 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 proteins test material derived from microbial cultures was 
biochemically and, functionally similar to the protein produced by the 
plant-incorporated protectant ingredients in corn. Production of 
microbially produced protein was chosen in order to obtain sufficient 
material for testing.
    The acute oral toxicity data submitted support the prediction that 
the Cry34Ab1 and Cry35Ab1 proteins would be non-toxic to humans. As 
mentioned above, when proteins are toxic, they are known to act via 
acute mechanisms and at very low dose levels (Sjoblad, Roy D., et al. 
``Toxicological Considerations for Protein Components of Biological 
Pesticide Products,'' Regulatory Toxicology and Pharmacology 15, 3-9 
(1992)). Since no effects were shown to be caused by the Cry34Ab1 and 
Cry35Ab1 proteins, even at relatively high dose levels, the Cry34Ab1 
and Cry35Ab1 proteins are not considered toxic. Basing this conclusion 
on acute oral toxicity data without requiring further toxicity testing 
and residue data is similar to the Agency position regarding toxicity 
and the requirement of residue data for the microbial Bacillus 
thuringiensis products from which these plant-incorporated protectants 
were 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).
    Cry34Ab1 and Cry35Ab1 proteins 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 
Cry34Ab1 and Cry35Ab1 proteins in corn tissues.
    Since Cry34Ab1 and Cry35Ab1 are proteins, their potential 
allergenicity is also considered as part of the toxicity assessment. 
Considering all of the available information (1) Cry34Ab1 and Cry35Ab1 
originate from a non-allergenic source; (2) Cry34Ab1 and Cry35Ab1 have 
no overall sequence similarities or homology at the level of eight 
contiguous amino acid residues with known allergens; (3) Cry34Ab1 and 
Cry35Ab1 are not glycoslyated when expressed in maize; (4) Cry34Ab1 and 
Cry35Ab1 will only be present at low levels in food; and (5) Cry35Ab1 
is rapidly digested in SGF, and Cry34Ab1 is digested at a moderate rate 
in SGF; EPA has concluded that the potential for the Cry34Ab1 and 
Cry35Ab1 proteins to be food allergens is minimal. The FIFRA Scientific 
Advisory Panel (SAP) that met on March 1-2, 2005 agreed with this 
conclusion regarding the allergenicity potential of Cry34Ab1. There 
were no triggers to raise concern about the allergenicity of Cry35Ab1, 
so the SAP was not asked to comment specifically on Cry35Ab1.
    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 Cry34Ab1 and Cry35Ab1 proteins, as well as the minimal 
potential to be a food allergen demonstrate the safety of the product 
at levels well above possible maximum exposure levels anticipated in 
the crop.
    The genetic material necessary for the production of the plant-
incorporated protectant active ingredients are the nucleic acids (DNA, 
RNA) which comprise genetic material encoding these proteins and their 
regulatory regions. The genetic material (DNA, RNA), necessary for the 
production of the Cry34Ab1 and Cry35Ab1 proteins have been exempted 
under the blanket exemption for all nucleic acids (40 CFR 174.475).

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 proteins 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, nor any indication of 
allergenicity potential for the plant-incorporated protectants.

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 the plant-incorporated protectants at this time.

B. Analytical Method(s)

    Validated enzyme-linked immunosorbent assays for the detection and 
quantification of Cry34Ab1 and Cry35Ab1 in corn tissue have been 
submitted and found acceptable by the Agency.

[[Page 55259]]

C. Codex Maximum Residue Level

    No Codex maximum residue levels exist for the plant-incorporated 
protectants Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins and 
the genetic material necessary for its 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) 
of the FFDCA, 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-2005-0211 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 November 
21, 2005.
    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 (1900L), 
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 Suite 350, 1099 14th St., 
NW., Washington, DC 20005. 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 (202) 564-6255.
    2. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit IX.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in ADDRESSES. Mail your 
copies, identified by docket ID number OPP-2005-0211 , to: Public 
Information and Records Integrity Branch, Information Technology and 
Resource Management 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 ADDRESSES. 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. 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

[[Page 55260]]

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.

X. 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 174

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

    Dated: August 29, 2005.
James Jones,
Director, Office of Pesticide Programs.

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

PART 174--[AMENDED]

0
1. The authority citation for part 174 continues to read as follows:

    Authority: 7 U.S.C. 136-136y; 21 U.S.C. 346a and 371.

0
2. Section 174.457 is added to subpart W to read as follows:


Sec.  174.457  Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins 
and the genetic material necessary for their production in corn; 
exemption from the requirement of a tolerance.

    Bacillus thuringiensis Cry34Ab1 and Cry35Ab1 proteins and the 
genetic material necessary for their production in corn are exempted 
from the requirement of a tolerance when used as plant-incorporated 
protectants in the food and feed commodities of corn; corn, field; 
corn, sweet; and corn, pop.

[FR Doc. 05-18582 Filed 9-20-05; 8:45 am]
BILLING CODE 6560-50-S