45620 Federal Register / Vol. 73, No. 152 / Wednesday, August 6, 2008 / Rules and Regulations 

Port at telephone number 617–223–3008 

or via on-scene patrol personnel on VHF 

channel 16 to seek permission to do so. 

If permission is granted, all persons and 

vessels must comply with the 

instructions of the Captain of the Port or 

his or her designated representative. 

Dated: July 24, 2008. 

Claudia C. Gelzer, 

Commander, U.S. Coast Guard, Acting 

Captain of the Port Boston, Massachusetts. 

[FR Doc. E8–18076 Filed 8–5–08; 8:45 am] 

BILLING CODE 4910–15–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 174 

[EPA–HQ–OPP–2007–0830; FRL–8374–2] 

Bacillus thuringiensis Vip3Aa Proteins 

in Corn and Cotton; 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 Vip3Aa proteins in or on 

the food and feed commodities of corn; 

corn, field; corn, sweet; corn, pop; and 

cotton; cotton, undelinted seed; cotton, 

refined oil; cotton, meal; cotton, hay; 

cotton, hulls; cotton, forage; and cotton, 

gin byproducts, when used as plantincorporated protectants in those food 

and feed commodities. Syngenta Seeds, 

Inc. 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 need to 

establish a maximum permissible level 

for residues of Bacillus thuringiensis 

Vip3Aa proteins in or on corn; corn, 

field; corn, sweet; corn, pop; and cotton, 

undelinted seed; cotton, refined oil; 

cotton, meal; cotton, hay; cotton, hulls; 

cotton, forage; and cotton, gin 

byproducts, when applied or used as 

plant-incorporated protectants. 

DATES: This regulation is effective 

August 6, 2008. Objections and requests 

for hearings must be received on or 

before October 6, 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–2007–0830. To access the 

electronic docket, go to http:// 

www.regulations.gov, select ‘‘Advanced 

Search,’’ then ‘‘Docket Search.’’ Insert 

the docket ID number where indicated 

and select the ‘‘Submit’’ button. Follow 

the instructions on the regulations.gov 

website to view the docket index or 

access available documents. All 

documents in the docket are listed in 

the docket index available in 

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: 

Alan Reynolds, Biopesticides and 

Pollution Prevention Division (7511P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001; telephone number: 

(703) 605–0515; e-mail address: 

reynolds.alan@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 an electronic 

copy of this Federal Register document 

through the electronic docket 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 180 

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, as 

amended by 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. 

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–2007–0830 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 October 6, 2008. 

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–2007–0830, 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’s 


yshivers on PROD1PC62 with RULES
Federal Register / Vol. 73, No. 152 / Wednesday, August 6, 2008 / Rules and Regulations 45621 

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 November 

2, 2007 (72 FR 62237) (FRL–8153–8), 

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 7F7254) 

by Syngenta Seeds, Inc., P.O. Box 

12257, 3054 E. Cornwallis Road, 

Research Triangle Park, NC 27709. The 

petition requested that 40 CFR part 180 

be amended by establishing an 

exemption from the requirement of a 

tolerance for residues of Bacillus 

thuringiensis Vip3Aa proteins in or on 

all food commodities when applied or 

used as plant-incorporated protectants. 

This notice included a summary of the 

petition prepared by the petitioner 

Syngenta Seeds, Inc. One comment was 

received in response to the notice of 

filing. The commenter objected to the 

petition and expressed concerns about 

EPA’s regulation of human exposure to 

toxic chemicals. The Agency 

understands the commenter’s concerns 

regarding toxic substances and the 

potential effects to humans. Pursuant to 

its authority under the FFDCA, and as 

discussed further in this Unit, EPA 

conducted a comprehensive assessment 

of representative Vip3Aa proteins, 

including a review of acute oral toxicity 

data on several Vip3Aa proteins, amino 

acid sequence comparisons to known 

toxins and allergens, as well as data 

demonstrating that the representative 

Vip3Aa proteins are rapidly degraded 

by gastric fluid in vitro, are not 

glycosylated, and are present in low 

levels in the tissues of the corn and 

cotton plants containing these plantincorporated protectants. Based on these 

data, the Agency has concluded that 

there is a reasonable certainty that no 

harm will result from dietary exposure 

to residues of these proteins in or on the 

food and feed commodities corn; corn, 

field; corn, sweet; corn, pop; and cotton, 

undelinted seed; cotton, refined oil; 

cotton, meal; cotton, hay; cotton, hulls; 

cotton, forage; and cotton, gin 

byproducts, when used as plantincorporated protectants in those food 

and feed commodities. Thus, under the 

standard in FFDCA section 408(b)(2), a 

tolerance exemption is appropriate. 

In taking this action, EPA, pursuant to 

its authority under section 

408(d)(4)(A)(i) of the FFDCA, is issuing 

a final regulation that varies from the 

regulation sought by petitioner Syngenta 

Seeds, Inc. Specifically, instead of 

issuing a tolerance exemption that 

covers residues of the subject plantincorporated protectant in all food 

commodities, EPA is issuing a tolerance 

exemption that covers such residues in 

those commodities in which it will be 

used as a plant-incorporated protectant 

– in this case, the food and feed 

commodities of corn; corn, field; corn, 

sweet; corn, pop; and cotton, undelinted 

seed; cotton, refined oil; cotton, meal; 

cotton, hay; cotton, hulls; cotton, forage; 

and cotton, gin byproducts. In this way, 

the tolerance exemption is coextensive 

with the registered uses for this 

particular plant-incorporated protectant. 

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. 

Mammalian toxicity and allergenicity 

assessment. Syngenta Seeds, Inc. has 

submitted acute oral toxicity data 

demonstrating the lack of mammalian 

toxicity at high levels of exposure to the 

Vip3Aa19 and Vip3Aa20 proteins. 

These data demonstrate the safety of 

these particular Vip3Aa proteins at 

levels well above the maximum possible 

exposure levels that are reasonably 

anticipated in cotton (Vip3Aa19) and 

corn (Vip3Aa20). 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 these plantincorporated protectants were derived 

(40 CFR 158.2140). For microbial 

products, further toxicity testing (Tiers 

II and III) and residue data are triggered 

by significant adverse acute effects in 

studies such as the mouse oral toxicity 

study, to verify the observed adverse 

effects and clarify the source of these 

effects. 

Syngenta submitted four acute oral 

toxicity studies conducted on mice. 

Three of the studies were conducted 

with microbially-produced Vip3Aa 

proteins (Vip3Aa1, Vip3Aa19, and 

Vip3Aa20) with slight variations in 

amino acid sequence (1-2 amino acid 

differences), and one study was 

conducted with transgenic corn leaf 

tissue expressing Vip3Aa19 as the test 

material. No treatment-related adverse 

effects were observed in any of the 

studies. The results of these studies 

showed that the oral LD50 for mice 

(males, females, and combined) was 

greater than 3,675 milligrams/kilogram/ 

body weight (mg/kg/bwt) (the highest 

dose tested) for the tested Vip3Aa 

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, pages 

3–9 (1992)). Therefore, since no acute 

effects were shown to be caused by the 

Vip3Aa19 and Vip3Aa20 proteins, even 

at relatively high dose levels, they are 

not considered toxic. (This is also true 


yshivers on PROD1PC62 with RULES
45622 Federal Register / Vol. 73, No. 152 / Wednesday, August 6, 2008 / Rules and Regulations 

of the Vip3Aa1 protein that was tested.) 

Further, amino acid sequence 

comparisons showed no similarities 

between Vip3Aa19 and Vip3Aa20, on 

the one hand, and known toxic proteins 

in protein databases, on the other hand, 

that would raise a safety concern. 

Since Vip3Aa 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 Vip3Aa 

follows: 

• Source of the trait. Bacillus 

thuringiensis, the microorganism from 

which Vip3Aa proteins are derived, is 

not considered to be a source of 

allergenic proteins. 

• Amino acid sequence. A 

comparison of the amino acid sequence 

of Vip3Aa19 and Vip3Aa20 with known 

allergens showed no significant 

sequence identity over 80 amino acids 

or identity at the level of eight 

contiguous amino acid residues. 

• Digestibility. Both Vip3Aa19 and 

Vip3Aa20 proteins are digested rapidly 

in simulated gastric fluid containing 

pepsin. 

• Glycosylation. Both Vip3Aa19 and 

Vip3Aa20 were shown not to be 

glycosylated. 

Considering all of the available 

information on Vip3Aa19 and 

Vip3Aa20, EPA concludes that the 

potential for these specific proteins to 

be food allergens is minimal. Moreover, 

as further explained below (and in 

section VI.a. of this final rule), EPA 

believes these data and the other 

submitted data demonstrating a lack of 

mammalian toxicity at high levels of 

exposure to Vip3Aa19 and Vip3Aa20 

can be extrapolated to cover Vip3Aa 

more generally. 

Vip3Aa is the designation assigned to 

a closely-related group of similar 

insecticidal proteins isolated from 

Bacillus thuringiensis. The specific 

variants referred to throughout this 

document (i.e., Vip3Aa19 and 

Vip3Aa20) are isolates of Vip3Aa 

protein. All Vip3Aa proteins (there are 

25 known Vip3Aa proteins and there are 

sequences available for 19 of these) are 

highly related. Indeed, the amino acid 

sequence of all the Vip3Aa proteins can 

only vary up to 5% to be considered a 

part of the Vip3Aa group. With respect 

to the 19 Vip3Aa proteins for which 

sequences are available, they vary by 

less than 28 amino acids out of the 789 

amino acids that make up the protein. 

This level of sequence similarity makes 

that group of 19 Vip3Aa protein variants 

96% identical overall. The sequence 

identity between any two individual 

sequences is even higher. For example, 

the sequences of the protein variants 

tested by Syngenta (i.e., Vip3Aa19 and 

Vip3Aa20) are over 99.7% identical. 

Finally, as to the few amino acid 

differences that do exist between the 

Vip3Aa variants, these differences do 

not alter the surrounding sequence, 

rarely occur as contiguous amino acids, 

and are often substitutions with similar 

chemical side groups indicating similar 

chemical functionality. Therefore, EPA 

finds that none of the Vip3Aa variants 

would be expected to have significant 

amino acid sequence identity — which 

is defined as either 35% identity over an 

80 amino acid stretch and, for allergens, 

at the level of eight contiguous amino 

acids — with a toxin, an anti-nutrient or 

an allergen. 

This conclusion is further supported 

by EPA’s overall safety assessment that 

includes other considerations such as 

the source of the trait, digestibility and 

glycosylation. As noted in this Unit, 

Bacillus thuringiensis (from which the 

Vip3Aa proteins are derived) is not 

considered to be a source of allergenic 

proteins. Furthermore, since all the 

Vip3Aa proteins have extremely 

homogenous structural similarities (as 

explained in this Unit), they are highly 

likely to show similar biochemical 

characteristics in terms of digestibility 

and glycosylation. So, as is the case for 

both Vip3Aa19 and Vip3Aa20, EPA 

expects that all Vip3Aa proteins will be 

rapidly digested under simulated gastric 

conditions and will not be glycosylated. 

Finally, it is also highly relevant here 

that microbial pesticide products, which 

are distinct from plant-incorporated 

protectant pesticide products, 

containing Bacillus thuringiensis and its 

components (which could include 

microbially-expressed Vip3Aa proteins) 

are already exempt from the 

requirement for a tolerance under 40 

CFR 180.1011. 

Accordingly, EPA believes that the 

foregoing supports EPA’s reasonable 

certainty of no harm finding not only for 

the Vip3Aa19 and Vip3Aa20 protein 

variants, but also for all other closelyrelated members of the Vip3Aa 

designation as described using the 

Crickmore classification system 

(Crickmore, N., Zeigler, D.R., Schnepf, 

E., Van Rie, J., Lereclus, D., Baum, J, 

Bravo, A. and Dean, D.H. ‘‘Bacillus 

thuringiensis toxin Nomenclature’’

(2007) http://www.lifesci.sussex.ac.uk/ 

Home/Neil_Crickmore/Bt/). 

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 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) to 

the pesticide chemical residue (i.e., the 

Vip3Aa proteins) 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 protectant’s 

chemical residue, and exposure from 

non-occupational sources. Exposure via 

the skin or inhalation is not likely since 

the plant-incorporated protectant is 

contained within plant cells, which 

essentially eliminates these exposure 

routes or reduces these exposure routes 

to negligible. In addition, even if 

exposure can occur through inhalation, 

the potential for Vip3Aa to be an 

allergen is low, as discussed in this 

Unit. Although the allergenicity 

assessment focuses on potential to be a 

food allergen, the data also indicate a 

low potential for Vip3Aa to be an 

inhalation allergen. Exposure via 

residential or lawn use to infants and 

children is also not expected because 

the use sites for Vip3Aa proteins are 

agricultural. Oral exposure, at very low 

levels, may occur from ingestion of food 

commodities containing Vip3Aa protein 

residues and, theoretically, drinking 

water. However oral toxicity testing (as 

discussed above) showed no adverse 

effects. 

V. Cumulative Effects 

Pursuant to FFDCA section 

408(b)(2)(D)(v), EPA has considered 

available information on the cumulative 

effects of residues of representative 

Vip3Aa proteins and other substances 

that have a common mechanism of 

toxicity. These considerations include 

the cumulative effects on infants and 

children of such residues and other 

substances with a common mechanism 

of toxicity. Because there is no 


yshivers on PROD1PC62 with RULES
Federal Register / Vol. 73, No. 152 / Wednesday, August 6, 2008 / Rules and Regulations 45623 

indication of mammalian toxicity 

resulting from exposure to Vip3Aa 

proteins, we conclude that there are no 

cumulative effects for the Vip3Aa 

proteins. 

VI. Determination of Safety for U.S. 

Population, Infants and Children 

1. Toxicity and allergenicity 

conclusions. The data submitted and 

cited regarding potential health effects 

for Vip3Aa proteins includes the 

characterization of representative 

Vip3Aa proteins, as well as the acute 

oral toxicity studies, amino acid 

sequence comparisons to known 

allergens and toxins, and in vitro 

digestibility of the representative 

Vip3Aa proteins. The results of these 

studies were used to evaluate humansk, 

and the validity, completeness, and 

reliability of the available data from the 

studies were also considered. 

Adequate information was submitted 

to show that the Vip3Aa test materials 

derived from microbial cultures were 

biochemically and functionally 

equivalent to the proteins produced by 

the plant-incorporated protectant 

ingredient in the plants. Microbially 

produced proteins were used in the 

studies so that sufficient material for 

testing was available. 

The acute oral toxicity data submitted 

for the representative Vip3Aa proteins 

support the prediction that Vip3Aa 

proteins will 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, pages 3–9 (1992)). 

Since no treatment-related adverse 

effects were shown to be caused by the 

representative Vip3Aa proteins, even at 

relatively high dose levels, Vip3Aa 

proteins are not considered toxic. 

Basing this conclusion on acute oral 

toxicity data without requiring further 

toxicity testing or residue data is similar 

to the Agency position regarding 

toxicity and the requirement of residue 

data for the microbial Bacillus 

thuringiensis products from which this 

plant-incorporated protectant was 

derived (see 40 CFR 158.2140). For 

microbial products, further toxicity 

testing (Tiers II and III) and residue data 

are triggered when significant adverse 

effects are seen in studies such as the 

acute oral toxicity study. Further studies 

verify the observed adverse effects and 

clarify the source of these effects. 

Residue chemistry data were not 

required for a human health effects 

assessment of the subject plantincorporated protectant ingredients 

because of the lack of mammalian 

toxicity. However, data submitted 

demonstrated low levels of the 

representative Vip3Aa proteins in corn 

and cotton tissues. 

Since Vip3Aa are proteins, potential 

allergenicity is also considered as part 

of the toxicity assessment. Considering 

all of the available information, 

including that: 

• Vip3Aa originates from a nonallergenic source. 

• Vip3Aa19 and Vip3Aa20 have no 

sequence similarities with known 

allergens. 

• Vip3Aa19 and Vip3Aa20 are not 

glycosylated. 

• Vip3Aa19 and Vip3Aa20 are 

rapidly digested in simulated gastric 

fluid. 

• The data developed for Vip3Aa19 

and Vip3Aa20 can be extrapolated to all 

Vip3Aa proteins due to the extremely 

high level of structural similarity that 

exists between and among Vip3Aa 

proteins, EPA has concluded that the 

potential for Vip3Aa to be an allergen is 

minimal. 

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 

representative Vip3Aa proteins, as well 

as the minimal potential to be a food 

allergen, demonstrate the safety of 

Vip3Aa at levels well above possible 

maximum exposure levels anticipated. 

The genetic material necessary for the 

production of the plant-incorporated 

protectant active ingredient include the 

deoxyribo nucleic acids/ribonucleic 

acid (DNA/RNA) that encode these 

proteins and regulatory regions. The 

genetic material DNA/RNA necessary 

for the production of Vip3Aa proteins 

has been exempted from the 

requirement of a tolerance under 40 CFR 

174.507 (Nucleic acids that are part of 

a plant-incorporated protectant; 

exemption from the requirement of a 

tolerance). 

2. 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 Vip3Aa proteins. Thus, there 

are no threshold effects of concern and, 

as a result, the provision requiring an 

additional tenfold margin of safety does 

not apply. Further, the considerations of 

consumption patterns, special 

susceptibility, and cumulative effects do 

not apply. 

3. 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 Vip3Aa proteins. 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 

Vip3Aa proteins. 

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 plantincorporated protectant at this time. 

B. Analytical Method(s) 

A lateral flow enzyme-linked 

immunosorbent assay (ELISA) protocol 

has been provided to the Agency for 

detecting Vip3Aa in cotton as well as a 

qualitative ELISA method for detecting 

Vip3Aa in corn. 

C. Codex Maximum Residue Level 

No Codex maximum residue level 

exists for the plant-incorporated 

protectant Bacillus thuringiensis 

Vip3Aa proteins and the genetic 

material necessary for their production 

in corn and cotton. 

VIII. Statutory and Executive Order 

Reviews 

This final rule establishes 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 


yshivers on PROD1PC62 with RULES
45624 Federal Register / Vol. 73, No. 152 / Wednesday, August 6, 2008 / Rules and Regulations 

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, 

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). 

IX. 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: June 26, 2008. 

Debra Edwards, 

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. Section 174.501 in subpart D is 

revised to read as follows: 

§ 174.501 Bacillus thuringiensis Vip3Aa 

protein in corn and cotton; exemption from 

the requirement of a tolerance. 

Residues of Bacillus thuringiensis 

Vip3Aa proteins in or on corn or cotton 

are exempt from the requirement of a 

tolerance when used as plant–

incorporated protectants in or on the 

food and feed commodities of corn; 

corn, field; corn, sweet; corn, pop; and 

cotton; cotton, undelinted seed; cotton, 

refined oil; cotton, meal; cotton, hay; 

cotton, hulls; cotton, forage; and cotton, 

gin byproducts. 

§ 174.528 [Removed] 

■ 3. Section 174.528 is removed from 

Subpart D. 

[FR Doc. E8–17931 Filed 8–5–08; 8:45 am] 

BILLING CODE 6560–50–S 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2008–0484; FRL–8375–5] 

Difenoconazole; Pesticide Tolerances 

for Emergency Exemptions 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes 

time-limited tolerances for residues of 

difenoconazole, 1-[2-[2-chloro-4-(4- 

chlorophenoxy)phenyl]-4-methyl-1,3- 

dioxolan-2-ylmethyl]-1H-1,2,4-triazole 

in or on almond, almond hulls, 

cantaloupe, cucumber, and watermelon. 

This action is in response to EPA’s 

granting crisis exemptions to the 

California Environmental Protection 

Agency and the Georgia Department of 

Agriculture under section 18 of the 

Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) authorizing 

use of the pesticide on almond, almond 

hulls, cantaloupe, cucumber, and 

watermelon. This regulation establishes 

a maximum permissible level for 

residues of difenoconazole in these food 

commodities. The time-limited 

tolerances expire and are revoked on 

December 31, 2011. 

DATES: This regulation is effective 

August 6, 2008. Objections and requests 

for hearings must be received on or 

before October 6, 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–2008–0484. To access the 

electronic docket, go to http:// 

www.regulations.gov, select ‘‘Advanced 

Search,’’ then ‘‘Docket Search.’’ Insert 

the docket ID number where indicated 

and select the ‘‘Submit’’ button. Follow 

the instructions on the regulations.gov 

website to view the docket index or 

access available documents. All 

documents in the docket are listed in 

the docket index available in 

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 either in the electronic docket 


yshivers on PROD1PC62 with RULES