Document ID: EPA-HQ-OPP-2016-0279-0004
Agency: epa
Document Type: Rule
Title: Tolerance Exemptions: Bacillus Thuringiensis (mCry51Aa2) Protein in or on Cotton
Posted Date: 2017-04-18T04:00Z

[Federal Register Volume 82, Number 73 (Tuesday, April 18, 2017)]
[Rules and Regulations]
[Pages 18226-18230]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-07804]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[EPA-HQ-OPP-2016-0279; FRL-9957-23]

Bacillus Thuringiensis (mCry51Aa2) Protein in or on Cotton; 
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 
mCry51Aa2 protein in or on the food and feed commodities of cotton; 
cotton undelinted seed; cotton, gin byproducts; cotton, forage; cotton, 
hay; cotton, hulls; cotton, meal; and cotton, refined oil, when used as 
a plant-incorporated protectant (PIP) in accordance with the terms of 
Experimental Use Permit (EUP) No. 524-108. Monsanto Company 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 mCry51Aa2 protein. The temporary tolerance exemption 
expires on February 28, 2019.

DATES: This regulation is effective April 18, 2017. Objections and 
requests for hearings must be received on or before June 19, 2017, 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: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2016-0279, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public 
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the Public 
Reading Room is (202) 566-1744, and the telephone number for the OPP 
Docket is (703) 305-5805. Please review the visitor instructions and 
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Robert McNally, Biopesticides and 
Pollution Prevention Division (7511P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave. NW., 
Washington, DC 20460-0001; main telephone number: (703) 305-7090; email 
address: BPPDFRNotices@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. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document

[[Page 18227]]

applies to them. Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR 
part 174 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 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. 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-2016-0279 in the subject line on the first 
page of your submission. All objections and requests for a hearing must 
be in writing, and must be received by the Hearing Clerk on or before 
June 19, 2017. Addresses for mail and hand delivery of objections and 
hearing requests are provided in 40 CFR 178.25(b).
    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 (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2016-0279, by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Background and Statutory Findings

    In the Federal Register of June 22, 2016 (81 FR 40594) (FRL-9947-
32), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance 
petition (PP 6G8453) by Monsanto Company, 800 North Lindbergh Blvd., 
St. Louis, MO 63167. The petition requested that 40 CFR part 174 be 
amended by establishing a temporary exemption from the requirement of a 
tolerance for residues of the plant-incorporated protein (PIP) Bacillus 
thuringiensis (mCry51Aa2.834_16 (mCry51Aa2) protein in or on cotton. 
That document referenced a summary of the petition prepared by the 
petitioner Monsanto Company, which is available in the docket, http://www.regulations.gov. One comment was received on the notice of filing. 
EPA's response to this comment is discussed in Unit VII.C.
    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 FFDCA 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 
FFDCA 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, FFDCA section 408(b)(2)(D) 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 FFDCA section 408(b)(2)(D), 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.
    Bacillus thuringiensis (Bt) Cry (or crystalline) proteins are 
naturally produced. These insecticidal proteins are protoxins, which 
must be activated by alkaline conditions in the insect gut, so they are 
not toxic until ingested by an insect. When activated, specific binding 
sites found only in susceptible host insects are involved in binding Bt 
protein toxins, followed by pore formation into the insect hemolymph, 
leakage and, in general, decreased vitality of the insect including 
reduced feeding, eventually causing mortality. Even among insects, 
specific Bt proteins are highly specific and so selection of specific 
proteins to target pests is possible often with little or no nontarget 
effects to humans or even to other insects.
    Bt proteins are also ubiquitous in soil and water and are found on 
food products which may be consumed with little processing. No adverse 
effects are expected or have been reported from exposure to Bt Cry 
proteins. Further, the use of Bt insecticidal proteins in bacterial and 
plant-incorporated formulations over time has been widely shown to be 
safe and nontoxic except to a limited range of target pests.
    Minor alterations to the native (or naturally produced) Cry51Aa2 
protein were made to make the protein Cry51Aa2.834_16 (hereafter 
referred to as modified Cry51Aa2 or mCry51Aa2) more active and specific 
to the target insect pests Lygus bugs and Thrips, when the protein is 
expressed in cotton plant tissues.
    Molecular analysis of mCry51Aa2 showed that it has a protein 
sequence that is 98% similar to Cry51Aa1 protoxin and 96% similar to 
the native Cry51Aa2 protoxin. Other sequence alignments, ranging from 
27 to 96%,

[[Page 18228]]

were to Bacillus proteins. Comparisons using the Basic Local Alignment 
Search Tool--protein query (BLASTp) database found 16 significant 
alignments, and all except the uncharacterized Jatropha curcas protein 
are from genus Bacillus. However, only three have identity >35% 
similarity and these are related insecticidal Bacillus thuringiensis 
Cry proteins/protoxins. Comparison of mCry51Aa2 to the native Cry51Aa2 
using the FASTA database shows three amino acids were deleted, and 
there are seven substitutions to the original 309 amino acids, 
resulting in a 306 amino acid protoxin. There were no sequences with 
any significant similarity (>35%) to known toxins other than the 
insecticidal protoxins from Bacillus thuringiensis.
    An acute oral toxicity test conducted with mice at the highest 
practicable dose of dose of 1332 mg of mCry51Aa2/Kg body weight was 
conducted in mice and showed no clinical signs of toxicity, no 
abnormalities on necropsy 14 days after treatment, and no statistically 
significant weight fluctuation. The No observed adverse effect level 
(NOAEL) was determined to be >1332 milligram (mg) of mCry51Aa2 per 
kilogram (kg) bodyweight.
    Rapid digestibility by pepsin was demonstrated (93.7% reduction 
within two minutes, and no detects at 60 minutes). Based on this assay 
it is likely that mCry51Aa2 would be completely digested in the human 
stomach.
    A thorough analysis of mCry51Aa2 shows it is not related to any 
other known allergens. Molecular analysis showed there were no 
significant full-length allergen sequence matches, and none showed 
significant similarity using a sliding 80 amino acid search or an exact 
8 amino acid match.
    Based on the results of these studies, no toxicity or other adverse 
effects from dietary exposure to mCry51Aa2 are expected.

IV. Aggregate Exposures

    In examining aggregate exposure, FFDCA section 408 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 considered available information on the aggregate 
exposure levels of consumers (and major identifiable subgroups of 
consumers) to the pesticide residue. These considerations include 
dietary exposure under the tolerance exemption in effect for the Bt 
mCry51Aa2 protein residue, and exposure from non-occupational sources. 
Oral exposure may occur at very low levels from ingestion of food and 
feed commodities of cotton. With respect to drinking water, since the 
PIP is integrated into the plant genome and based upon EPA's human 
health and environmental assessments for Bt mCry51Aa2 protein (Refs. 1 
and 2), the Agency expects residues in drinking water to be extremely 
low or non-existent.
    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 exposure by 
these routes to negligible. Exposure to infants and children via 
residential or lawn use is also not expected because the use is limited 
to agricultural production of cotton with the Bt mCry51Aa2 protein PIP.

V. Cumulative Effects From Substances With a Common Mechanism of 
Toxicity

    Section 408(b)(2)(D)(v) of FFDCA requires that, when considering 
whether to establish, modify, or revoke a tolerance, 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 has not found mCry51Aa2 protein to share a common mechanism of 
toxicity with any other substances, and mCry51Aa2 protein does not 
appear to produce a toxic metabolite produced by other substances. For 
the purposes of this tolerance action, therefore, EPA has assumed that 
mCry51Aa2 protein does not have a common mechanism of toxicity with 
other substances. For information regarding EPA's efforts to determine 
which chemicals have a common mechanism of toxicity and to evaluate the 
cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

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

    FFDCA section 408(b)(2)(C) provides that, in considering the 
establishment of a tolerance or tolerance exemption for a pesticide 
chemical residue, 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) provides that EPA shall apply an additional 
tenfold (10X) margin of exposure (safety) for infants and children in 
the case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the database on toxicity and exposure 
unless EPA determines that a different margin of exposure (safety) will 
be safe for infants and children. This additional margin of exposure 
(safety) is commonly referred to as the Food Quality Protection Act 
Safety Factor (FQPA SF). In applying this provision, EPA either retains 
the default value of 10X or uses a different additional safety factor 
when reliable data available to EPA support the choice of a different 
factor.
    Based on the information discussed in Unit III., EPA concludes that 
there are no threshold effects of concern to infants, children, or 
adults from exposure to the Bt mCry51Aa2 protein. As a result, EPA 
concludes that no additional margin of exposure (safety) is necessary 
to protect infants and children and that not adding any additional 
margin of exposure (safety) will be safe for infants and children.
    Therefore, based on the discussion in Units III. and IV. and the 
supporting documentation, EPA concludes that there is a reasonable 
certainty that no harm will result to the U.S. population, including 
infants and children, from aggregate exposure to the residues of the Bt 
mCry51Aa2 protein in cotton products, when it is used as a plant-
incorporated protectant. Such exposure includes all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.

VII. Other Considerations

A. Analytical Enforcement Methodology

    A standard operating procedure for an enzyme-linked Immunosorbent 
assay (ELISA) for the detection and quantification of the Bt mCry51Aa2 
protein in cotton tissue has been submitted.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint United Nations 
Food and Agriculture Organization/World Health Organization food 
standards program, and it is recognized as an international food safety 
standards-setting

[[Page 18229]]

organization in trade agreements to which the United States is a party. 
EPA may establish a tolerance that is different from a Codex MRL; 
however, FFDCA section 408(b)(4) requires that EPA explain the reasons 
for departing from the Codex level.
    The Codex has not established a MRL for the Bt protein mCry51Aa2 
protein.

C. Response to Comments

    In response to the Notice of Filing (81 FR 40594), one comment was 
received and posted August 05, 2016. It urged the Agency deny the 
request for ``Bt Cry51Aa2'' because ``the release of more protein on 
earth is harmful because our nature exists with a certain set of 
standards.'' The commenter did not provide any more information on the 
set of standards governing our nature. In response to this comment, the 
Agency notes that protein is an important component of the diet of 
humans and animals and that Monsanto Company has submitted information 
to address the potential for the mCry51Aa protein to be similar to a 
known allergen or toxin utilizing amino acid similarity analysis. There 
is no indication from the information provided that the mCry51Aa 
protein would behave differently from any other dietary protein.
    One additional comment about human health effects was received not 
in response to the Notice of Filing, but in response to the Notice of 
Receipt for this Experimental Use Permit (81 FR 48793; see docket EPA-
HQ-OPP-2016-0282). Because it raised a concern about human health 
effects, the EPA is responding to it in this document. The comment 
stated that that . . . numerous studies show toxicity of Bt products 
including GM Bt crops to other non-target including . . . rats as well 
as allergenic and respiratory problems in humans . . .'' While not all 
of the numerical citations were provided, it was possible to retrieve 
several. Some articles (``Ban GMOs Now'' and ``New GMO Studies 
Demonstrate `Substantial Non-Equivalance'') were not from peer-reviewed 
journals and are of questionable validity for the issue of mCry51Aa 
safety. There was a reference to an article about the presence of Bt 
toxins in the blood of non-pregnant and pregnant females as well as in 
fetal cord blood. This article by Aris & Leblanc (Repro Tox. 31:528-
533, 2011) has some important design limitations which question the 
implications made in the paper about blood levels of Cry1Ab protein. 
Most importantly, there were no identified effects in the population 
sampled that indicates any health concerns related to the presence of 
the Cry1Ab protein in blood.
    Overall there is no substantive information in either of these 
comments to inform the risk assessment for mCry51Aa2.

VIII. Conclusions

    The Agency concludes that there is a reasonable certainty that no 
harm will result to the U.S. population, including infants and 
children, from aggregate exposure to residues of mCry51Aa2 protein in 
or on cotton. 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 previously no toxicity 
to mammals has been observed, nor is there any indication of 
allergenicity potential for the plant-incorporated protectant, and 
there is a long history of human exposure to Bacillus thuringiensis 
bacteria and toxins through naturally occurring residues and residues 
from use as a pesticide in agricultural and residential settings and in 
other plant incorporated protectants. Therefore, a temporary exemption 
is established for residues of the PIP Bacillus thuringiensis mCry51Aa2 
protein on the food and feed commodities derived from cotton containing 
the PIP.

IX. References

1. U.S. EPA. 2016a. MON 88702 Cotton Expressing B. thuringiensis 
mcry51Aa2 Protein Stacked with the Vip3Aa19, Cry2Ab2 and Cry1Ac 
Proteins Memorandum from J. Gagliardi, Ph.D. through J. Kough, Ph.D. 
to A. Sibold, dated September 12, 2016.
2. U.S. EPA. 2016b. Environmental Risk Assessment for a FIFRA 
Section 5 Experimental Use Permit for MON 88702 Alone and in 
Combination with Other Registered Plant Incorporated Protectants in 
Cotton. Memorandum from S. Borges, Senior Scientist to A. Sibold, 
Regulatory Action Leader, dated October 19, 2016.
3. U.S. EPA. 2016c. Review of Public Comments on Cry51Aa Notice of 
Filing Experimental Use Permit and Associated Temporary Tolerance 
(6G8453). November 2, 2016.

X. Statutory and Executive Order Reviews

    This action establishes a tolerance under FFDCA section 408(d) 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 action has been 
exempted from review under Executive Order 12866, this action 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 action 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 FFDCA section 408(d), 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 action 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 FFDCA section 408(n)(4). 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 action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    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 (NTTAA) (15 U.S.C. 272 note).

XI. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
EPA will

[[Page 18230]]

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 the rule in the 
Federal Register. This action 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: January 10, 2017.
Robert McNally,
Division Director, Biopesticides and Pollution Prevention Division, 
Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 174--AMENDED

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

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

0
 2. Add Sec.  174.536 to subpart W to read as follows:

Sec.  174.536  Bacillus thuringiensis mCry51Aa2 protein in cotton; 
temporary exemption from the requirement of a tolerance.

    Residues of the protein mCry51Aa2 in or on the food and feed 
commodities of cotton: Cotton, undelinted seed; cotton, gin byproducts; 
cotton, forage; cotton, hay; cotton, hulls; cotton, meal; and cotton, 
refined oil are temporarily exempt from the requirement of a tolerance 
when used as a plant-incorporated protectant in cotton plants in 
accordance with the terms of Experimental Use Permit No. 524-EUP-108. 
This temporary exemption from the requirement of a tolerance expires on 
February 28, 2019.

[FR Doc. 2017-07804 Filed 4-17-17; 8:45 am]
 BILLING CODE 6560-50-P