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:

SUBMISSION

: E

- mail the completed template to:

TEMPLATE:

J.R. Simplot Company

5G8375

EPA has received a pesticide petition 5G8375 from J.R. Simplot Company

, 5369 W. Irving St., Boise, ID 83706 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish an amendment/expansion of an existing tolerance exemption for the plant

pesticide the VNT1 protein product of the Rpi

- vnt1 gene in or on potato

. Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, J.R. Simplot Company has submitted the following summary of information, data, and arguments in support of their pesticide petition. Th is summary was prepared by J.R. Simplot Company 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 uni ntentionally made the reader conclude that the findings reflected EPA’s position and not the position of the petitioner.

I. J.R. Simplot Company Petition Summary

5G8375

A. Product Name and Proposed Use Practices

Potato containing the VNT1 protein . The VNT1 protein is expressed from the Rpi

- vnt1 gene and confers resistance to Phytophthora infestans , the cause of late blight disease in potato.

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues

.

The active ingredient that provides late blight resistance in potato is the VNT1 protein produced from the Rpi

- vnt1 resistance gene. The Rpi

- vnt1 gene is from the wild potato species, Solanum venturii

.

 Name: Rpi

- vnt1 Resistance Gene and VNT1 protein. Chem ical Identity: Nucleic acid (including promoter, coding sequence, and terminator) and translated amino acid polypeptide.

 Composition: Potato events were generated by Agrobacterium

- mediated plant transformation. Confirmation of gene insertion was carried out using PCR, Southern blot, and immunoblot methods based on the gene and protein sequences.

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

residue

.

Less than 30 ppb in tubers as determined by immunoblot detection

. It is estimated that the active ingredient, VNT1 protein, is less than 0.000003% of potato.

3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed.

The VNT1 protein concentration is lower than the detectable limit of 30 ppb in

tubers

. As the expression levels of the VNT1 protein are below detection limits it is impractical t o demonstrate methods for detecting and measuring the levels of the pesticide residues.

C. Mammalian Toxicological Profile

Safety assessments of the VNT1 protein and Rpi

- vnt1 resistance gene were carried out to determine the mode of action, history of safe use, similarity to known toxins or allergens, and expression levels in planta . These safety assessments demonstrate the safety of the VNT1 protein.

Proteins are not inherently toxic due to rapid denaturation by the acidic conditions of the stomach, and degradation by proteases secreted in the intestinal tract.

Resistance genes (R

- genes) have a non

- toxic mode of action and are found in multiple plant species, includi ng: Solanum melongena L. (eggplant), Capsicum annum L. (pepper), Solanum lycopersicum L. (tomato), Solanum tuberosum L. (potato), Zea mays (maize), Glycine max (soybean), Oryza sativa L. (rice), and Triticum aestivum L. (wheat).

R

- genes are an important pa rt of a plants immune response to pathogen infection . They

are protein receptors that recognize and bind pathogen

- secreted proteins. Upon pathogen recognition, a form of programmed cell death is activated causing infected plant cells to die, blocking the s pread of infection.

A NCBI database search for homologs of the VNT1 protein and the Rpi

- vnt1 gene identified potato and tomato genes with high sequence similarity. An example is the tomato gene Tm

- 2, which provides resistance to the tomato mosaic virus ( TMV), and is

90% similar to Rpi

- vnt1 in nucleic acid sequence. The encoded proteins Tm

- 2 and VNT1 are 75% identical in amino acid sequence. A search of tomato variety databases and retailwebsites show seventy

- eight varieties and two rootstocks of TMV resi stant tomato. These

examples demonstrate a history of safe use for proteins similar to VNT1.

A bioinformatics analysis showed no sequence similarity between the VNT1 protein or any known allergen or toxin.

A sensitive immunoblot method was used to determine that the VNT1 protein is expressed at levels below the detection limit of 30 ppb in tubers. It is estimated that the active ingredient, VNT1 protein, is less than 0.000003% of potato. Effects on humans

an d on non

- target organisms, including plants, insects, mammals, birds, and aquatic life would be negligible because of the lack of exposure.

D

. Aggregate Exposure

1. Dietary exposure.

The VNT1 protein is similar to other proteins to which people are exposed in their

diet without adverse effects. Because of the low express ion levels of the VNT1 protein

the exposure to humans is negli gible.

i. Food.

The VNT1 protein is expressed in potato. Human exposur e is expected from eating potato. The VNT1 protein is not similar to any known allergens or toxins. The VNT1 protein is expressed at low levels . The low exposure minimize s risk associated with the VNT1 protein.

ii. Drinking water

.

Human exposure is not expected through drinking water.

2. Non

- dietary exposure

.

The VNT1 protein is a plant

- incorporated protectant. Other uses where human exposure might occur are not intended or expected.

E . Cumulative Effects

Human exposure to the VNT1 protein from diet, food, drinking water, or other occupational or residential use is negligible.

F . Safety Determination

1. U.S. population.The VNT1 protein is unlikely to pose risk to human health. Study reports

assessing the safety of the VNT1 protein demonstrate a non

- toxic mode of action for the VNT1 protein, a history of safe use for homologous proteins in potato and tomato, and no significant sequence similarities between VNT1 and known allergens or toxins. The VNT1 protein concentration was shown t o be below detectable limits, less than 30 ppb in tubers. Defining a tolerance limit for the VNT1 protein is not practical considering the low expression and low exposure risk of the VNT1 protein.

2. Infants and children

.

The VNT1 protein is unlikely t o pose risk to infants or children.

G. Effects on the Immune and Endocrine Systems

The VNT1 protein is unlikely to cause effects on the immune and endocrine

systems.

H. Existing Tolerances

A current temporary exemption from the requirement of a tolerance [EPA

- HQ

OPP

- 2014

- 0457; FRL

- 9922

- 53] established for residues of the VNT1 protein in potato expires on December 31, 2015.

I . International Tolerances

None.