Document ID: EPA-HQ-OPP-2007-0573-0003
Agency: epa
Document Type: Rule
Title: Bacillus thuringiensis Cry2Ae in Cotton; Temporary Exemption from the Requirement of a Tolerance
Posted Date: 2008-09-10T04:00Z

[Federal Register: September 10, 2008 (Volume 73, Number 176)]
[Rules and Regulations]               
[Page 52591-52594]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10se08-7]                         

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[EPA-HQ-OPP-2007-0573; FRL-8380-1]

 
Bacillus thuringiensis Cry2Ae in Cotton; Temporary Exemption from 
the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes a temporary exemption from the 
requirement of a tolerance for residues of the Bacillus thuringiensis 
Cry2Ae in or on cotton and its food and feed commodities when used as a 
Plant-Incorporated Protectant (PIP) in accordance with the terms of 
Experimental Use Permit 264-EUP-143. Bayer CropScience LP submitted a 
petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), 
requesting the temporary tolerance exemption. This regulation 
eliminates the need to establish a maximum permissible level for 
residues of Bacillus thuringiensis Cry2Ae. The temporary tolerance 
exemption expires on December 31, 2012.

DATES: This regulation is effective September 10, 2008. Objections and 
requests for hearings must be received on or before November 10, 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-2007-0573. All documents in the 
docket are listed in the docket index available at http://
www.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: Shanaz Bacchus, Biopesticides and 
Pollution Prevention Division (7511P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001; telephone number: (703) 308-8097; e-mail 
address: bacchus.shanaz@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 electronically available documents 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 174 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, 21 U.S.C. 346a, 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-2007-0573 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 10, 2008.

[[Page 52592]]

    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-2007-0573, 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 Facility's normal hours of operation (8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays). 
Special arrangements should be made for deliveries of boxed 
information. The Docket Facility telephone number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of August 8, 2007 (72 FR 44521-44523) (FRL-
8139-7), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance 
petition (PP 7F7192) by Bayer CropScience LP, P.O. Box 12014, 2 T.W. 
Alexander Dr., Research Triangle Park, NC 27709. The petition requested 
that 40 CFR be amended by establishing a temporary exemption from the 
requirement of a tolerance for residues of Bacillus thuringiensis 
Cry2Ae in or on cotton when used as a Plant-Incorporated Protectant 
(PIP). Bayer has requested an Experimental Use Permit (EUP), EPA File 
Symbol 264-EUP-143, under which it seeks to use Cry2Ae as a PIP on 
1,919 acres of cotton. A summary of the petition prepared by the 
petitioner was included in the docket. There were no comments received 
in response to the notice of filing.
    Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an 
exemption from the requirement for a tolerance (the legal limit for a 
pesticide chemical residue in or on a food) only if EPA determines that 
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of FFDCA defines 
``safe '' to mean that ``there is a reasonable certainty that no harm 
will result from aggregate exposure to the pesticide chemical residue, 
including all anticipated dietary exposures and all other exposures for 
which there is reliable information.'' This includes exposure through 
drinking water and in residential settings, but does not include 
occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in 
establishing or maintaining in effect an exemption from the requirement 
of a tolerance, EPA must take into account the factors set forth in 
section 408(b)(2)(C) of FFDCA, which require EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical 
residue....'' Additionally, section 408(b)(2)(D) of FFDCA requires that 
the Agency consider ``available information concerning the cumulative 
effects of a particular pesticide's residues'' and ``other substances 
that have a common mechanism of toxicity.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other exposures that occur as 
a result of pesticide use in residential settings.

III. Toxicological Profile

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action and considered its validity, completeness and reliability 
and the relationship of this information to human risk. EPA has also 
considered available information concerning the variability of the 
sensitivities of major identifiable subgroups of consumers, including 
infants and children.
    The following toxicological profile is based on summaries of the 
Agency's reviews of the petitioner's data submissions (Ref. 1).

A. Acute Oral Toxicity

    Bayer CropScience has submitted acute oral toxicity data 
demonstrating the lack of mammalian toxicity at high levels of exposure 
to the pure Cry2Ae protein. An acute oral toxicity study in mice 
indicated that Cry2Ae is non-toxic to humans. The acute oral toxicity 
of Cry2Ae was assessed by administering Bacillus thuringiensis-produced 
Cry2Ae protein by oral gavage at a dose of 2,000 milligrams/kilogram of 
body weight (mg/kg b.w.) to groups of five female mice. There were no 
mortalities, and no treatment-related adverse effects observed. 
Therefore, the acute oral LD50 of the Cry2Ae protein is 
greater than 2,000 mg/kg body weight (Ref. 2).
    For microbial products, further toxicity tests and residue data 
(Tiers II and III) are only required to verify and clarify adverse 
effects observed during Tier I testing. In the submitted studies for 
this PIP, no adverse acute effects were observed in the Tier I acute 
oral or acute injection studies. Therefore, Tier II and Tier III 
studies were not required. Thus, EPA concluded that these data 
demonstrate the safety of the product at a level well above maximum 
possible exposure levels that are reasonably anticipated in the crop. 
Basing this conclusion on acute oral toxicity data without requiring 
further toxicity testing and residue data is similar to the Agency 
position regarding toxicity testing and the requirement of residue data 
for the microbial Bacillus thuringiensis products from which this PIP 
was derived (See 40 CFR 158.2140).
    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 Cry2Ae, even at relatively high dose levels, 
the Cry2Ae protein is not considered toxic. Further, amino acid 
sequence comparisons showed no similarities between the Cry2Ae and 
known toxic proteins in protein databases that would raise a safety 
concern.

B. Cry2Ae Allergenicity Assessment

    Since Cry2Ae 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 Cry2Ae is based on the potential of the 
source of the protein, the similarity of its amino acid sequence to 
known allergens, its glycosylation and its digestibility. The applicant 
submitted data to demonstrate that Cry2Ae: (1) Originates from a non-
allergenic source (Ref. 4); (2) has no sequence similarities with known

[[Page 52593]]

allergens (Ref. 5); (3) is not glycosylated (Ref. 6); and (4) is 
rapidly digested in simulated gastric fluid (Ref. 7). Thus EPA has 
concluded that the potential for Cry2Ae to be an allergen is minimal 
(Ref. 1).

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).

A. Dietary Exposure--Food and Drinking Water

    As discussed in Unit III, laboratory tests show that Cry2Ae 
demonstrates a very low to minimal acute oral toxicity and 
allergenicity potential. Thus, EPA does not expect any harm to human 
adults, infants and children exposed to Cry 2Ae via consumption of food 
commodities related to cotton.
    Oral exposure, at very low levels, may occur from ingestion of 
processed cotton products and, theoretically, drinking water. Based on 
the lack of adverse effects during the acute oral toxicity study 
conducted in mice (LD50 greater than 2,000 mg/kg), the 
Agency does not expect any harm via dietary exposure, including 
exposure to drinking water.

B. Other Non-Occupational Exposure--Dermal and Inhalation

    Non-occupational dermal and inhalation exposure is expected to be 
negligible or non-existent.
    Exposure via the skin or inhalation is not likely since the Plant-
Incorporated Protectant is contained within plant cells. Thus, exposure 
and risk via dermal and inhalation routes are essentially negligible or 
eliminated. In addition, even if exposure can occur through inhalation, 
the potential for Cry2Ae to be an allergen is low, as discussed above 
in Unit III. Although the allergenicity assessment focuses on potential 
to be a food allergen, the data also indicate a low potential for 
Cry2Ae to be an inhalation allergen. Furthermore, non-occupational 
dermal and inhalation exposure via residential or lawn use to human 
adults, infants and children is also not expected because the use sites 
for the Cry2Ae protein are agricultural.

V. Cumulative Effects

    Pursuant to FFDCA section 408(b)(2)(D)(v), EPA has considered 
available information on the cumulative effects of such residues and 
other substances that have a common mechanism of toxicity. These 
considerations included the cumulative effects on infants and children 
of such residues and other substances with a common mechanism of 
toxicity. Because there is no indication of mammalian toxicity from the 
Plant-Incorporated Protectant, we conclude that there are no cumulative 
effects for the Cry2Ae protein.

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 Cry2Ae protein include the characterization of the expressed Cry2Ae 
protein in cotton, as well as the acute oral toxicity study, amino acid 
sequence comparisons to known allergens and toxins, and in vitro 
digestibility of the protein. The results of these studies were used to 
evaluate human risk, and the validity, completeness, and reliability of 
the available data from the studies were also considered.
    The acute oral toxicity data submitted support the prediction that 
the Cry2Ae protein would be non-toxic to humans. As mentioned above in 
Unit III no treatment-related adverse effects were shown to be caused 
by the Cry2Ae protein, even at relatively high dose levels and Tier I 
studies showed no adverse effects. Thus, Tiers II and III studies were 
not required and the Cry2Ae protein is not considered toxic.
    Since Cry2Ae is a protein, potential allergenicity is also 
considered as part of the toxicity assessment. Considering all of the 
available information: (1) Cry2Ae originates from a non-allergenic 
source; (2) Cry2Ae has no sequence similarities with known allergens; 
(3) Cry2Ae is not glycosylated; and (4) Cry2Ae is rapidly digested in 
simulated gastric fluid; EPA has concluded that the potential for 
Cry2Ae to be an allergen is minimal.
    The lack of mammalian toxicity at high levels of exposure to the 
Cry2Ae protein, 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.

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 Cry2Ae 
protein. Thus, there are no threshold effects of concern and, as a 
result, the provision requiring an additional margin of safety does not 
apply. Further, the considerations of consumption patterns, special 
susceptibility, and cumulative effects do not apply.

C. Overall Safety Conclusion

    There is a reasonable certainty that no harm will result from 
aggregate exposure to the U.S. population, including infants and 
children, to the Cry2Ae protein. This includes all anticipated dietary 
exposures and all other exposures for which there is reliable 
information. The Agency has arrived at this conclusion because, as 
discussed above, no toxicity to mammals has been observed, nor any 
indication of allergenicity potential for the Plant-Incorporated 
Protectant.

VII. Other Considerations

A. Endocrine Disruptors

    The pesticidal active ingredient is a protein, derived from a 
source that is not known to exert an influence on the endocrine system. 
Therefore, the Agency is not requiring information on the endocrine 
effects of the Plant-Incorporated Protectant, Bacillus thuringiensis 
Cry2Ae protein at this time.

B. Analytical Method(s)

    Because this is only a temporary exemption from the requirement of 
a tolerance, EPA is not requiring an analytical detection method at 
this time.

C. Codex Maximum Residue Level

    No Codex Maximum Residue Level (MRL) exists at this time for the 
Plant-Incorporated Protectant Bacillus thuringiensis Cry2Ae protein.

[[Page 52594]]

VIII. References

    1. USEPA BPPD memorandum dated February 12, 2008 from Rebecca 
Edlestein to Shanaz Bacchus.
    2. Master Record Identification Number (MRID No.) 47076902, USEPA, 
BPPD memo 2/12/2008).
    3. Sjoblad, Roy D., et al., ``Toxicological Considerations for 
Protein Components of Biological Pesticide Products,'' Regulatory 
Toxicology and Pharmacology 15, 3-9 (1992).
    4. MRID 47125101.
    5. MRID 46708903.
    6. MRIDs 46708903 and 46708907.
    7. MRIDs 46708905 and 47125102.

IX. Statutory and Executive Order Reviews

    This final rule establishes an exemption from the requirement of a 
tolerance under section 408(d) of FFDCA in response to a petition 
submitted to the Agency. The Office of Management and Budget (OMB) has 
exempted these types of actions from review under Executive Order 
12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 
1993). Because this final rule has been exempted from review under 
Executive Order 12866, this final rule is not subject to Executive 
Order 13211, entitled Actions Concerning Regulations That Significantly 
Affect Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001) 
or Executive Order 13045, entitled Protection of Children from 
Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 
1997). This final rule does not contain any information collections 
subject to OMB approval under the Paperwork Reduction Act (PRA), 44 
U.S.C. 3501 et seq., nor does it require any special considerations 
under Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under section 408(d) of FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply.
    This final rule directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled Federalism (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 9, 2000) do not apply to this final rule. In addition, 
this final rule does not impose any enforceable duty or contain any 
unfunded mandate as described under Title II of the Unfunded Mandates 
Reform Act of 1995 (UMRA) (Public Law 104-4).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 
note).

X. Congressional Review Act

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

List of Subjects in 40 CFR Part 174

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

    Dated: August 25, 2008.
Marty Monell,
Acting 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 174.530 is added to subpart W to read as follows:

Sec.  174.530  Bacillus thuringiensis Cry2Ae protein in cotton; 
Temporary exemption from the requirement of a tolerance.

    Residues of Bacillus thuringiensis Cry2Ae protein in or on the food 
commodities of cotton, cotton; cotton, undelinted seed; cotton, refined 
oil; cotton, meal; cotton, hay; cotton, hulls; cotton, forage; and 
cotton, gin byproducts are exempt temporarily from the requirement of a 
tolerance when Bacillus thuringiensis Cry2Ae protein in cotton plants 
is used as a Plant-Incorporated Protectant in accordance with the terms 
of Experimental Use Permit 264-EUP-143. This temporary exemption from 
the requirement of a tolerance will expire on December 31, 2012.
[FR Doc. E8-20728 Filed 9-9-08; 8:45 am]

BILLING CODE 6560-50-S