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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- 

## 17 1 (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 efeeti"t • e ingredient] 2. bieehemieel pestieide 

### [iasert aeme efaetive iflgredient] 3. plant-pesticide 

### Bacillus thuringiensis CrylF 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 ofinfortnation,**dat~** and arguments in support oftheir pesticide petition. This summary was prepared by Dow AgroSciences LLC and EPA has not fully evaluated the merits ofthe pesticide petition. The summary may have been edited by EPA ifthe 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 ofthe petitioner

. I. Dow AgroSciences LLC Petition Summary [Insert petition number] 

## 2.**Fro~** 

### co A. Product Name andProposed Use Practices This notice offiling 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 thepesticide and corresponding residues

. The CrylF }litltt;i'l expressed in soybean originates from the naturally occurring soil bacterium Bacillus thuringiensis

. The transgene for CryIF protein expression was introduced if)t•>**~oybean** via Agrobacterium-mediated transformation. The soybean-derived Cry1 F protein was shown to be biochemically and biologically equivalent to the microbial

-derived CryIF protein which was used in the safety assessment studies. The Cry1 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 ofthe magnitude ofresidue 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 thepesticide 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 Cryproteins 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 from3
the requirement ofa 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. Cry1F 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 hea lth effects from acute or chronic exposure is virtually nonexistent. Proteins in general are not known to be carcinogens

. A search ofrelevant databases indicated that the amino acid sequence ofthe Cry1F protein exhibits no significant homology to the sequences ofknown protein toxins

. In addition, there was no homology with sequences ofknown allergens and the Cry1F protein was not glycosylated inplanta. Therefore, the Cry1 F protein is highly unlikely to exhibit an allergic response. The genetic material necessary for the production ofthe Cry1F protein are nude1c acids which are common to all forms ofplants and animals. There are no known instances ofwhere nucleic acids have caused toxic effects as a result ofdietary exposure. Collectively, the available data on the Cry1 F protein along with a proven safe :ISC ofmicrobial Bacillus thuringiensis products establishes the safety ofthe 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 ofprocessed commodities, although they may occur, is unlikely to be problematic because oflow toxicity and high degree ofdigestibility ofthe 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 ofthe Cry1F protein is contained within the plant making any route ofoxposure other than ingestion very unlikely. E. Cumulative Effects Common modes oftoxicity are not relevant to consideration ofthe 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 ofthe 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 ofCrylF protein expressed within the plant, the non-toxic nature ofthe protein d Bacillus thuringiensis Cry proteins in general , the high degree ofdigestibility, e lack ofnon-dietary exposure, and the lack ofallergenic 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 ofthe CrylF protein. Due to the lack of toxicity, the lack ofallergenic potential, the high degree ofdigestibility ofCrylF 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 ofthe 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 ofa tolerance for the plan: - incorporated protectant Bacillu s 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

.