I 

EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION 

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN 

THE FEDERAL REGISTER 

EPA Biopesticides and Pollution Prevention Division contact: Sheryl Reilly, 703-

308-8269 

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert "NA-Remove" and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., " [insert 

company name]," with the information specific to your action. 

SUBMISSION: Email the completed template to: hollis.linda@epa.gov. 

TEMPLATE: 

Dow AgroSciences LLC 

[Insert petition number] 2...F 30b" 

2P2"06~ 

EPA has received a pesticide petition ([insert petition number]) fror.1 U: w 

AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268 requesting, pursuant t'1 

section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 

346a(d), to amend 40 CFR part .l-8(1- 171 

(Options (pick one) 

l. by establishing a telertmee fer residl:les ef 

2. to establish an exemption from the requirement of a tolerance for 

3. te establ-ish an amendmes&'expansieft efan existiHg teleranee exemptiea fer the 

(Options (pick one) 

I. mierebial pestieide [iasert aame ef eeti"t•e ingredient] 

2. bieehemieel pestieide [iasert aeme ef aetive iflgredient] 

3. plant-pesticide Bacillus thuringiensis Cryl F protein as expressed in or on 

soybean. 
2 

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, Dow AgroSciences LLC has 

submitted the following summary of infortnation, dat~ and arguments in support of their 

pesticide petition. This summary was prepared by Dow AgroSciences LLC and EPA has 

not fully evaluated the merits of the pesticide petition. The summary may have been 

edited by EPA if the terminology used was unclear, the summary contained extraneous 

material, or the summary unintentionally made the reader conclude that the findings 

reflected EPA's position and not the position of the petitioner. 

I. Dow AgroSciences LLC Petition Summary 

[Insert petition number] 2. Fro~ co 

A. Product Name and Proposed Use Practices 

This notice of filing summarizes the information submitted and cited by Dow 

AgroSciences LLC in support of a request for an exemption from the requirement of~ 

tolerance for the Bacillus thuringiensis CrylF protein as expressed in soybean. 

B. Product Identity/Chemistry 

1. Identity of the pesticide and corresponding residues. The CrylF }litltt;i'l 

expressed in soybean originates from the naturally occurring soil bacterium Bacillus 

thuringiensis. The transgene for Cry IF protein expression was introduced if)t•> ~oybean 

via Agrobacterium-mediated transformation. The soybean-derived Cry 1 F protein was 

shown to be biochemically and biologically equivalent to the microbial-derived Cry IF 

protein which was used in the safety assessment studies. The Cry 1 F protein poses no 

foreseeable risks to non-target organisms. 

2. Magnitude of residues at the time of harvest and method used to determine the 

residue. No information is included because a determination of the magnitude of residue 

at harvest is not required for residues exempt from tolerance. 

3. A statement of why an analytical method of detecting and measuring the levels 

of the pesticide residue are not needed. No analytical method is included because this 

petition requests an exemption from the requirement of a tolerance. 

C. Mammalian Toxicological Profile 

Cry proteins have been deployed as safe and effective pest control agents in 

microbial Bacillus thuringiensis formulations for more than 40 years. There have been 

more than 150 registered microbial Badllus thuringiensis products in the United States 

for use in agriculture, forestry, and vector control. The numerous toxicology studies 

conducted with these microbial products show no significant adverse effects, and 

demonstrate that the products are practically non-toxic to mammals. An exemption from 
3 

the requirement of a tolerance has been in place for these products since at least 1971 ( 40 

CFR 180.1011). 

Toxicology studies conducted to determine the toxicity ofCry1F protein 

demonstrated that the protein has very low toxicity. In an acute oral toxicity study in 

mice, high doses ofCry1F protein revealed no adverse effects. In an in vitro study, Cry1F 

protein was rapidly and extensively degraded in simulated gastric fluid in the presence of 

pepsin at pH 1.2. Cry1 F was completely proteolyzed to amino acids and small peptide 

fragments in less than 1 minute. This indicates that Cry1F protein is highly susceptible to 

digestion in the human digestive tract and that the potential for adverse health effects 

from acute or chronic exposure is virtually nonexistent. 

Proteins in general are not known to be carcinogens. A search of relevant 

databases indicated that the amino acid sequence of the Cry1F protein exhibits no 

significant homology to the sequences of known protein toxins. In addition, there was no 

homology with sequences of known allergens and the Cry1F protein was not glycosylated 

in planta. Therefore, the Cry1 F protein is highly unlikely to exhibit an allergic response. 

The genetic material necessary for the production of the Cry1F protein are nude1c 

acids which are common to all forms of plants and animals. There are no known 

instances of where nucleic acids have caused toxic effects as a result of dietary exposure. 

Collectively, the available data on the Cry1 F protein along with a proven safe :ISC 

of microbial Bacillus thuringiensis products establishes the safety of the CrylF ~JroteiP . 

D. Aggregate Exposure 

1. Dietary exposure. 

i. Food. The level ofCrylF protein expressed in soybean is very low therefore 

significant dietary exposure to Cry1F protein is unlikely to occur. Dietary exposure at 

very low levels via ingestion of processed commodities, although they may occur, is 

unlikely to be problematic because oflow toxicity and high degree of digestibility of the 

protein. 

ii. Drinking water. The Cry1 F protein is unlikely to be present in drinking water 

because the protein is present in minute quantities within the plant and does not persist in 

soil. 

2. Non-dietary exposure. The small amount of the Cry1F protein is contained 

within the plant making any route of oxposure other than ingestion very unlikely. 

E. Cumulative Effects 

Common modes oftoxicity are not relevant to consideration of the cumulative 

exposure to Bacillus thuringiensis CrylF protein. Cry1F protein is readily digested in 

simulated gastric fluid and has demonstrated very low mammalian toxicity. Further, 
4 

Bacillus thuringiensis Cry proteins are known to have specific modes of action which do 

not affect humans, such that the biological effects of the CrylF protein do not appear to 

be cumulative with any other known compounds. 

F. Safety Determination 

1. U.S. population. Considering the minute q tities of Cryl F protein expressed 

within the plant, the non-toxic nature of the protein d Bacillus thuringiensis Cry 

proteins in general, the high degree of digestibility, e lack of non-dietary exposure, and 

the lack of allergenic potential, Dow AgroScience oncludes that the risk posed by 

CrylF protein to the U.S. population is insignificant. 

2. Infants and children. Non-dietary exposure to infants and children is not 

anticipated due to the proposed use pattern of the CrylF protein. Due to the lack of 

toxicity, the lack of allergenic potential, the high degree of digestibility of Cryl F protein, 

dietary exposure is anticipated to be at very low levels and is not anticipated to pose any 

harm to infants and children. 

G. Effects on the Immune and Endocrine Systems 

The CrylF protein is derived from a naturally occurring soil bacterium Bacillus 

thuringiensis not known to exert an influence on the immune or endocrine system. Given 

the characteristics of the CrylF protein as described above, the potential fof eiTe- ts on the 

immune or endocrine systems is highly unlikely. 

H. Existing Tolerances 

EPA established an exemption from the requirement of a tolerance for the plan:-

incorporated protectant Bacillus thuringiensis CrylF protein in cotton (40 CFR 

§ 174.504) and in com ( 40 CFR § 174.520). 

I. International Tolerances 

No maximum residue levels have been established for the Cry IF protein under the 

Codex Alimentarius.