Federal Register / Vol. 78, No. 27 / Friday, February 8, 2013 / Rules and Regulations 9317 

the CAA. Accordingly, this action 

merely approves state law as meeting 

Federal requirements and does not 

impose additional requirements beyond 

those imposed by state law. For that 

reason, this action: 

• Is not a ‘‘significant regulatory 

action’’ subject to review by the Office 

of Management and Budget under 

Executive Order 12866 (58 FR 51735, 

October 4, 1993); 

• does not impose an information 

collection burden under the provisions 

of the Paperwork Reduction Act (44 

U.S.C. 3501 et seq.); 

• is certified as not having a 

significant economic impact on a 

substantial number of small entities 

under the Regulatory Flexibility Act (5 

U.S.C. 601 et seq.); 

• does not contain any unfunded 

mandate or significantly or uniquely 

affect small governments, as described 

in the Unfunded Mandates Reform Act 

of 1995 (Pub. L. 104–4); 

• does not have Federalism 

implications as specified in Executive 

Order 13132 (64 FR 43255, August 10, 

1999); 

• is not an economically significant 

regulatory action based on health or 

safety risks subject to Executive Order 

13045 (62 FR 19885, April 23, 1997); 

• is not a significant regulatory action 

subject to Executive Order 13211 (66 FR 

28355, May 22, 2001); 

• is not subject to requirements of 

Section 12(d) of the National 

Technology Transfer and Advancement 

Act of 1995 (15 U.S.C. 272 note) because 

application of those requirements would 

be inconsistent with the CAA; and 

• does not provide EPA with the 

discretionary authority to address, as 

appropriate, disproportionate human 

health or environmental effects, using 

practicable and legally permissible 

methods, under Executive Order 12898 

(59 FR 7629, February 16, 1994). 

In addition, this rule does not have 

tribal implications as specified by 

Executive Order 13175 (65 FR 67249, 

November 9, 2000), because the SIP is 

not approved to apply in Indian country 

located in the state, and EPA notes that 

it will not impose substantial direct 

costs on tribal governments or preempt 

tribal law. 

B. Submission to Congress and the 

Comptroller General 

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. Section 804, 

however, exempts from section 801 the 

following types of rules: rules of 

particular applicability; rules relating to 

agency management or personnel; and 

rules of agency organization, procedure, 

or practice that do not substantially 

affect the rights or obligations of nonagency parties. 5 U.S.C. 804(3). Because 

this is a rule of particular applicability, 

EPA is not required to submit a rule 

report regarding this action under 

section 801. 

C. Petitions for Judicial Review 

Under section 307(b)(1) of the CAA, 

petitions for judicial review of this 

action must be filed in the United States 

Court of Appeals for the appropriate 

circuit by April 9, 2013. Filing a petition 

for reconsideration by the Administrator 

of this final rule does not affect the 

finality of this action for the purposes of 

judicial review nor does it extend the 

time within which a petition for judicial 

review may be filed, and shall not 

postpone the effectiveness of such rule 

or action. Parties with objections to this 

direct final rule are encouraged to file a 

comment in response to the parallel 

notice of proposed rulemaking for this 

action published in the proposed rules 

section of today’s Federal Register, 

rather than file an immediate petition 

for judicial review of this direct final 

rule, so that EPA can withdraw this 

direct final rule and address the 

comment in the proposed rulemaking. 

This action to approve a revision to 

the Maryland SIP to remove the Mount 

Saint Mary’s College 1979 Consent 

Order from the SIP may not be 

challenged later in proceedings to 

enforce its requirements. (See section 

307(b)(2).) 

List of Subjects in 40 CFR Part 52 

Environmental protection, Air 

pollution control, Incorporation by 

reference, Particulate matter. 

Dated: January 25, 2013. 

W.C. Early, 

Acting Regional Administrator, Region III. 

40 CFR part 52 is amended as follows: 

PART 52—[AMENDED] 

■ 1. The authority citation for part 52 

continues to read as follows: 

Authority: 42 U.S.C. 7401 et seq. 

Subpart V—Maryland 

§ 52.1070 [Amended] 

■ 2. In § 52.1070, the table in paragraph 

(d) is amended by removing the entry 

for Mt. Saint Mary’s College. 

[FR Doc. 2013–02817 Filed 2–7–13; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 174 

[EPA–HQ–OPP–2012–0795; FRL–9376–4] 

Glycine max Herbicide-Resistant 

Acetolactate Synthase; 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 Glycine 

max herbicide-resistant acetolactate 

synthase (GM–HRA) enzyme when used 

as a plant-incorporated protectant inert 

ingredient in or on the food and feed 

commodities of soybean. Pioneer HiBred International, Inc. (DuPont 

Pioneer), submitted a petition to EPA 

under the Federal Food, Drug, and 

Cosmetic Act (FFDCA), requesting an 

exemption from the requirement of a 

tolerance. This regulation eliminates the 

need to establish a maximum 

permissible level for residues of Glycine 

max herbicide-resistant acetolactate 

synthase enzyme in or on the food and 

feed commodities of soybean. 

DATES: This regulation is effective 

February 8, 2013. Objections and 

requests for hearings must be received 

on or before April 9, 2013, 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–2012–0795, 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), EPA West 

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 


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9318 Federal Register / Vol. 78, No. 27 / Friday, February 8, 2013 / Rules and Regulations 

the visitor instructions and additional 

information about the docket available 

at http://www.epa.gov/dockets. 

FOR FURTHER INFORMATION CONTACT: 

Susanne Cerrelli, Biopesticides and 

Pollution Prevention Division (7511P), 

Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave. NW., Washington, 

DC 20460–0001; telephone number: 

(703) 308–8077; email address: cerrelli.

susanne@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 

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–2012–0795 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 April 9, 2013. 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– 

2012–0795, 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.htm. 

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 November 

7, 2012 (77 FR 66781) (FRL–9367–5), 

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 2E8059) 

by Pioneer Hi-Bred International, Inc. 

(DuPont Pioneer), 7100 NW., 62nd 

Avenue, P.O. Box 1000, Johnston, Iowa, 

50131. The petition requested that 40 

CFR part 174 be amended by 

establishing an exemption from the 

requirement of a tolerance for residues 

of Glycine max herbicide-resistant 

acetolactate synthase (GM–HRA) when 

used as a plant-incorporated protectant 

(PIP) inert ingredient in or on the food 

and feed commodities of soybean. That 

document referenced a summary of the 

petition prepared by the petitioner, 

Pioneer Hi-Bred International, Inc. 

(DuPont Pioneer), which is available in 

the docket, http://www.regulations.gov. 

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 

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. 

A. Product Characterization Overview 

Acetolactate synthase (ALS) protein, 

also known as acetohydroxyacid 

synthase (AHAS), is a key enzyme that 

catalyzes the first common step in the 

biosynthesis of the essential branchedchain amino acids, and is obligatory for 

plant development. The gene that 

encodes the GM–HRA protein, gm-hra, 

is derived from the gm-als I gene, a 

naturally occurring soybean gene that 

encodes for acetolactate synthase I (GM– 

ALS I) protein. Changes were made in 

the DNA gene sequence for gm-als I to 

produce gm-hra. The modified gene was 

then introduced into the plant’s genome 

through particle bombardment (with the 

PHP30987A fragment). The GM–HRA 


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Federal Register / Vol. 78, No. 27 / Friday, February 8, 2013 / Rules and Regulations 9319 

protein is 604 amino acids in length, 

with a predicted molecular weight of 65 

kilodaltons (kDa), and is >99% 

homologous with the native GM–ALS I 

protein produced in soybeans. This 

minor modification of the endogenous 

GM–ALS I protein to GM–HRA protein 

yields an enzyme that is resistant to 

ALS-inhibiting herbicides. Thus, the 

GM–HRA protein will be useful as a 

selectable marker in soybean 

transformation events. As part of a 

genetic construct introduced into a 

plant’s genome, GM–HRA itself does not 

have insecticidal activity and is 

therefore functionally inert as part of a 

PIP. Potentially, GM–HRA also might 

serve as an herbicide-tolerant trait in 

soybeans, a use over which the U.S. 

Department of Agriculture (USDA) has 

separate regulatory jurisdiction. 

B. Mammalian Toxicity Assessment 

DuPont Pioneer, has submitted acute 

oral toxicity data demonstrating the lack 

of mammalian toxicity at relatively high 

levels of exposure to the pure GM–HRA 

protein. These data demonstrate the 

safety of the product at a level well 

above maximum possible exposure 

levels that are reasonably anticipated in 

the crop (Ref. 1). 

An acute oral toxicity study in mice 

indicated that GM–HRA is nontoxic 

(Ref. 2). Two groups of five males and 

five females mice were orally dosed (via 

gavage) with 2,000 milligrams/kilograms 

body weight (mg/kg bwt) of the test 

substance, a biochemically and 

functionally equivalent, microbially 

produced GM–HRA protein. There were 

no adverse clinical signs or findings at 

necropsy in the test animals. 

When proteins are toxic, they are 

known to act via acute mechanisms and 

at very low dose levels (Ref. 3). Since no 

acute oral effects were shown to be 

caused by GM–HRA, even at relatively 

high dose levels (up to 2,000 mg/kg 

bwt), the GM–HRA protein is not 

considered to be toxic. In support of this 

conclusion, amino acid sequence 

comparisons between the GM–HRA 

protein and known toxic proteins in 

protein databases found no similarities 

that would contradict the results of the 

acute oral study. 

C. Allergenicity Assessment 

Since GM–HRA is a protein, 

allergenic sensitivities were considered. 

Currently, no definitive tests exist for 

determining the allergenic potential of 

novel proteins. Current scientific 

knowledge suggests that common food 

allergens tend to be resistant to 

degradation by acid and proteases; they 

also may be glycosylated, and are 

present at high concentrations in food. 

Using a ‘‘weight-of-evidence’’ approach, 

EPA considered the source of the trait, 

amino acid sequence similarity with 

known allergens, its prevalence in food, 

and biochemical properties of the 

protein, including in vitro digestibility 

in simulated gastric fluid (SGF), and 

glycosylation (Ref. 4). The results of the 

EPA’s analysis are as follows: 

1. Source of the trait. The donor 

organism is Glycine max (soybean), 

which has an endogenous gene (gm-als 

I) that encodes for acetolactate synthase 

I (GM–ALS I) protein. Although soybean 

is one of the major food allergens, none 

of the known soy allergens is a member 

of the ALS protein family, including 

ALS protein. ALS enzymes are widely 

distributed in nature, and als genes have 

been isolated from bacteria, fungi, algae 

and plants (Refs. 5, 6, 7, and 8). Amino 

acid sequencing (BLASTP analysis) 

yielded 12,451 structurally or 

functionally related protein accessions 

(Ref. 9).The gm-hra gene, coding for the 

proposed PIP inert ingredient GM–HRA 

protein, was produced by transforming 

the naturally occurring, herbicidesensitive gm-als I genetic sequence. The 

new gene was introduced into the plant, 

and the resulting herbicide-tolerant 

GM–HRA protein differs from the ALS 

I protein by only two amino acids. Both 

of the two amino acid substitutions in 

GM–HRA are already present in 

commercially available crop varieties 

(soybean, sunflower, maize, and canola 

(Refs. 10, 11, 12 and 13)) that are 

naturally tolerant to ALS-inhibiting 

herbicides. 

2. Amino acid sequence. A 

comparison of the amino acid sequence 

of GM–HRA with known allergens 

found no significant overall sequence 

similarity or identity at the level of eight 

contiguous amino acid residues, the 

level of sensitivity needed to detect 

potential allergens. 

3. Prevalence in food. ALS enzymes 

have been part of the human diet by 

virtue of their presence in soybeans and 

other commercial food crops (soybean, 

maize, wheat, rice, and canola). Some of 

these enzymes contain natural 

mutations that include the same two 

amino acid substitutions as GM–HRA 

protein that render them tolerant to 

ALS-inhibiting herbicides (Ref. 12), and 

no ALS-related food allergies have been 

reported. 

4. Digestibility. The GM–HRA protein 

was rapidly digested (in less than 30 

seconds) in simulated mammalian 

gastric fluid (which has a highly acidic 

pH of 1.2 and includes the protein 

digesting enzyme, pepsin, found in 

gastric fluid) after incubation at 37 °C. 

5. Glycosylation. The GM–HRA 

protein expressed in soybean is not 

glycosylated. Considering all of the 

available information, EPA has 

concluded that the potential for GM– 

HRA to be a food allergen is minimal. 

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 nonoccupational 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, 

including infants and children, to the 

proposed pesticide PIP inert residue, 

GM–HRA protein, and to other related 

substances. This protein is an enzyme 

produced in soybean by a gene that was 

genetically derived from a naturally 

occurring soybean gene that encodes an 

herbicide-sensitive ALS enzyme. The 

altered gene is reinserted into soybean, 

and the resulting GM–HRA protein has 

greater than 99% similarity with the 

natural herbicide-sensitive protein 

enzyme, differing only in two amino 

acids (Ref. 13). These minor changes 

confer resistance of the enzyme to 

herbicidal pesticides that inhibit ALS 

enzymes, which is what allows the GM– 

HRA protein to be used as a selectable 

herbicide-tolerant marker in soybean 

transformation events. The two amino 

acid substitutions found in the 

engineered GM–HRA protein also occur 

as natural mutations in other 

commercially available, non-genetically 

modified crop varieties that are tolerant 

to ALS-inhibiting herbicides, and thus 

human exposure to the naturally 

occurring protein, in addition to the 

proposed PIP inert, is anticipated. The 

only route of human exposure that is 

likely, however, is through the human 

diet, since the proposed PIP inert 

ingredient (and the related naturally 

occurring ALS enzymes) is contained 

within plant cells, which reduces 

potential human exposure via other 

routes to negligible. Exposure via 

residential or lawn use is not expected 

because the intended use sites are all 

agricultural. Though highly unlikely, 

should residues of GM–HRA appear in 

drinking water as a result of its use as 

a PIP inert ingredient in soybean, the 

risk to humans would be very unlikely, 

based on the protein’s lack of 

mammalian toxicity demonstrated in 

the acute oral toxicity study and the 

lack of amino acid similarity with 


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9320 Federal Register / Vol. 78, No. 27 / Friday, February 8, 2013 / Rules and Regulations 

known protein toxins and allergens (see 

Unit III). 

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.’’ 

Based on the results of acute toxicity 

testing, EPA concluded that the 

proposed PIP inert, GM–HRA, is not 

toxic. EPA also concluded that no toxic 

or allergenic metabolites are produced 

in soybean or other edible crops from 

the activity of this catabolic enzyme. In 

addition, GM–HRA as encoded by the 

gm-hra gene was previously evaluated 

for its safety by the U.S. Food and Drug 

Administration (FDA) in two other 

transgenic soybean events. In one event, 

the gene was modified to produce high 

oleic soybean oil (OECD Unique ID No. 

DP–3;5423–1), and the other provided 

glyphosate and ALS-inhibiting 

herbicide tolerance (OECD Unique ID 

No. DP–356;43–5) (Refs.14 and 15). 

Based upon the information submitted, 

FDA concluded that the safety profiles 

of these soybean events, the GM–HRA 

protein were not materially different 

from that of other marketed soybean 

varieties, and no safety concerns with 

the protein were identified (Refs.16 and 

17). 

EPA concludes that there are no 

cumulative effects associated with GM– 

HRA expected from the proposed use as 

a PIP inert ingredient in soybean. 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 

The data submitted and cited 

regarding potential health effects for the 

GM–HRA protein include the 

characterization of the expressed GM– 

HRA protein in soybean, as well as the 

acute oral toxicity, amino acid sequence 

comparisons, and in vitro digestibility 

study. The results of these studies were 

used to evaluate human risk, and the 

validity, completeness, and reliability of 

the available data from the studies was 

considered. 

As discussed in unit III, the acute oral 

toxicity data submitted supports the 

prediction that the GM–HRA protein 

would be nontoxic to humans. 

Moreover, amino acid sequence analysis 

demonstrated that GM–HRA was not 

similar to any known protein toxin or 

allergen. Other data considered as part 

of the allergenicity assessment included: 

The structural and functional similarity 

of GM–HRA protein with naturally 

occurring ALS proteins from soybean 

and other food crops; the ALS proteins 

are not associated with food 

allergenicity; the protein rapidly 

degraded in the highly acidic 

digestibility study; and GM–HRA 

protein not glycosylated when 

expressed in the plant. GM–HRA 

protein is therefore not expected to be 

a human allergen. 

Finally, and specifically with regard 

to infants and children, 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) 

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 data base unless 

EPA determines that a different margin 

of safety will be safe for infants and 

children. 

Based on its review and consideration 

of all the available information, 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 the GM–HRA 

protein and the genetic material 

necessary for its production when used 

as a PIP inert ingredient in or on food 

and feed commodities of soybean. This 

includes all anticipated dietary 

exposures and all other exposures for 

which there is reliable information. The 

Agency has also concluded, for the 

reasons discussed in more detail above, 

that there are no threshold effects of 

concern and, as a result, that an 

additional margin of safety for infants 

and children is unnecessary in this 

instance. 

VII. Other Considerations 

A. Analytical Enforcement Methodology 

An analytical method is not required 

for enforcement purposes since the 

Agency is establishing an exemption 

from the requirement of a tolerance 

without any numerical limitation. 

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 

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 GM–HRA protein in soybean. 

VIII. Conclusions 

Therefore, an exemption from the 

requirement of a tolerance is established 

for residues of Glycine max herbicideresistant acetolactate synthase (GM– 

HRA) enzyme in or on the food and feed 

commodities of soybean when used as 

a plant-incorporated protectant inert 

ingredient. 

IX. References 

1. U.S. EPA. 2012. Review of Product 

Characterization and Human Health Data 

for Glycine max Herbicide-Tolerant 

Acetolactate Synthase (GM–HRA) 

protein expressed in Event 82117 

soybean (OECD Unique ID. DP–;82117– 

3) in support of an Exemption from the 

Requirement of a Tolerance (Petition No. 

2E8059) when used as a PlantIncorporated Protectant (PIP) Inert 

Ingredient in soybean. Memorandum 

from A. Waggoner, and J. Kough, Ph.D. 

to S. Cerrelli. (Dated December 20, 2012). 

2. Finlay, C. (2006) GM–HRA: Acute Oral 

Toxicity Study in Mice. Study Report 

No. PHI–2006–008, Unpublished study 

prepared by E.I. du Pont de Nemours and 

Company, August 9, 2006. 41 pgs. MRID 

No. 48872004. 

3. Sjoblad, R.D., J.T. McClintock, and R. 

Engler (1992) ‘‘Toxicological 

Considerations for Protein Components 

of Biological Pesticide Products,’’ 

Regulatory Toxicology and 

Pharmacology 15:3–9. 

4. CAC (2003) Alinorm 03/34: Joint FAO/ 

WHO Food Standard Programme. Codex 

Alimentarius Commission, Twenty-Fifth 

Session, 30 July 2003. Rome, Italy. 

Appendix III: Guideline for Conduct of 

Food Safety Assessments of Foods 

Derived from Recombinant-DNA Plants; 

Appendix IV: Annex on Assessment of 

Possible Allergenicity. CAC, 47–60. 


wreier-aviles on DSK7SPTVN1PROD with RULES
Federal Register / Vol. 78, No. 27 / Friday, February 8, 2013 / Rules and Regulations 9321 

5. Friden, P., Donegan, J., Mullen, J., Tsui, P., 

Freundlich, M., Eoyang, L., Weber, R., 

and Silverman, P.M. (1985) The ilvB 

locus of Escherichia coli K–12 is an 

operon encoding both subunits of 

acetohydroxyacid synthase I. Nucleic 

Acids Research 13: 3979–3993. 

6. Falco, S.C., Dumas, K.D., and Livak, K.J. 

(1985) Nucleotide sequence of the yeast 

ILV2 gene which encodes acetolactate 

synthase. Nucleic Acids Research 13: 

4011–4027. 

7. Reith, M. and Munholland, J. (1995) 

Complete nucleotide sequence of the 

Porphyra purpurea chloroplast genome. 

Plant Molecular Biology Reporter 7: 333– 

335. 

8. Mazur, B., Chiu, C.F., and Smith, J.E. 

(1987) Isolation and characterization of 

plant genes coding for acetolactate 

synthase, the target enzyme for two 

classes of herbicides. Plant Physiology 

85: 1110–1117. 

9. Krauss, A. (2012) Evaluation of the Amino 

Acid Sequence Similarity of the GM– 

HRA Protein to the NCBI Protein 

Sequence Datasets. Study Report No. 

PHI–2006–071/070. Unpublished study 

prepared by Pioneer Hi-Bred 

International, Inc., January 23, 2012. 

8251 pgs. MRID No. 48872006. 

10. Sebastian, S.A., Fader, G.M., Ulrich, J.F., 

Forney, D.R., Chaleff R.S. (1989) 

Semidominant Soybean Mutation for 

Resistance to Sulfonylurea Herbicides. 

Crop Science 29:1403–1408. 

11. Lee, K.Y., Townsend, J., Tepperman, J., 

Black, M., Chiu, C.F., Mazur, B., 

Dunsmuir, P., and Bedbrook, J. (1988) 

The molecular basis of sulfonylurea 

herbicide resistance in tobacco. EMBO 

Journal 7(5): 1241–1248. 

12. Tan, S., Evans, R., and Singh, B. (2006) 

Herbicidal inhibitors of amino acid 

biosynthesis and herbicide-tolerant 

crops. Amino Acids 30: 195–204. 

13. Locke, M., Cressman, B., Lu, A., 

Mathesius, C., Rood, T., and Sanders, C. 

(2012) Description, Derivation, Mode of 

Action and Familiarity of the GM–HRA 

Enzyme. Study Number: PHI–2012–020. 

Unpublished study prepared by Pioneer 

Hi-bred International, Inc., June 25, 

2012. 22 pgs. MRID No. 48872003. 

14. US–FDA (2007a) Biotechnology 

Consultation Note to the File BNF No. 

000108. U.S. Food and Drug 

Administration, http://www.fda.gov/ 

Food/Biotechnology/Submissions/ 

ucm155604.htm. 

15. US–FDA (2009a) Biotechnology 

Consultation Note to the File BNF No. 

000110. U.S. Food and Drug 

Administration, http://www.fda.gov/ 

Food/Biotechnology/Submissions/ 

ucm155595.htm. 

16. US–FDA (2007b) Biotechnology 

Consultation Agency Response Letter 

BNF No. 000108. U.S. Food and Drug 

Administration, http://www.fda.gov/ 

Food/Biotechnology/Submissions/ 

ucm155575.htm. 

17. US–FDA (2009b) Biotechnology 

Consultation Agency Response Letter 

BNF No. 000110. U.S. Food and Drug 

Administration, http://www.fda.gov/ 

Food/Biotechnology/Submissions/ 

ucm155567.htm. 

X. Statutory and Executive Order 

Reviews 

This final rule 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 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 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 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 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 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) (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 of 1995 

(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 

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 17, 2013. 

Steven Bradbury, 

Director, Office of Pesticide Programs. 

Therefore, 40 CFR chapter I is 

amended as follows: 

PART 174—[AMENDED] 

■ 1. The authority citation for part 174 

continues to read as follows: 

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

■ 2. Add § 174.533 to subpart W to read 

as follows: 

§ 174.533 Glycine max Herbicide-Resistant 

Acetolactate Synthase (GM–HRA) inert 

ingredient; exemption from the requirement 

of a tolerance. 

Residues of Glycine max herbicideresistant acetolactate synthase (GM– 

HRA) enzyme in or on the food and feed 

commodities of soybean are exempt 

from the requirement of a tolerance 

when used as a plant-incorporated 

protectant inert ingredient. 

[FR Doc. 2013–02699 Filed 2–7–13; 8:45 am] 

BILLING CODE 6560–50–P 


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