 EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

J.R. Simplot Company

EPA Reg. #8917

       EPA has received a pesticide petition #5F8425, 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 VNTl protein product of the Rpi-vntl  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. This 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 unintentionally 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

   #5F8425
 
 Product Name and Proposed Use Practices

 The W8 Russet Burbank, X17 Ranger Russet, and Y9 Atlantic Potato varieties, containing the VNTl protein. The VNT l protein is expressed from the Rpi-vntl  gene originating from Solanum venturii and confers resistance to Phytophthora infestans, the cause of late blight disease in potato.

 Product Identity/ Chemistry

       Identity of the pesticide and corresponding residues.

The active ingredient that provides late blight resistance in potato is the VNTl protein produced from the Rpi-vntl  resistance gene from Solanum venturii.

 Name: Rpi-vntl  Resistance Gene and VNTl protein.

 Chemical 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.

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

 Less than 100 ppb in tubers as determined by immunoblot detection. It is estimated that the active ingredient, VNTl protein, is less than 0.00001% of potato.

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

 The VNTl protein concentration is less than 100 ppb in tubers. As the expression levels of the VNTl protein are below detection limits it is impractical to demonstrate methods for detecting and measuring the levels of the pesticide residues.

 C. Mammalian Toxicological Profile

 Assessments of the VNTl protein and Rpi-vntl resistance gene were carried out to determine the mode of action, history of safe use, similarity to known toxins or allergens, and expression levels inplanta. No safety concerns of the VNTl  protein were identified.

 Proteins are not inherently toxic and are rapidly denatured by the acidic conditions of the stomach and 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, including: Solanum melongena L. (eggplant), Capsicum annum L. (pepper), S. lycopersicum L. (tomato), S. tuberosum L. (potato), Zea mays (maize), Glycine max (soybean), Oryza saliva L. (rice), and Triticum aestivum L. (wheat). R-genes are an important part 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 spread of infection.

 A NCBI database search for homologs of the VNTl protein and the Rpi-vntl gene identified potato and tomato genes with high sequence similarity. An example is the tomato gene Tm-22, which provides resistance to the tomato mosaic virus (TMV), and is 90% similar to Rpi-vntl in nucleic acid sequence. The encoded proteins Tm-22  and VNTl are 75% identical in amino acid sequence. A search of tomato variety databases and retail websites show seventy-eight varieties and two rootstocks of TMV resistant tomato. These examples demonstrate a history of safe use for proteins similar to VNTl.


 A bioinformatics analysis showed no sequence similarity between the VNTl protein or any known allergen or toxin demonstrating a low hazard to humans.

 A sensitive immunoblot method was used to determine that the VNTl protein is expressed at less than 100 ppb in tubers. It is estimated that the active ingredient, VNTl protein, is less than 0.00001% of potato. Effects on humans and on non-target organisms, including plants, insects, mammals, birds, and aquatic life would be negligible because of the lack of exposure.

 Aggregate Exposure

 Dietary exposure.

 The VNTl protein is similar to other proteins to which people are exposed in their diet without adverse effects. Because of the low expression levels of the VNTl protein
 the exposure to humans is negligible.

       i.Food.

 The VNTl protein is expressed in potato. Human exposure is expected from eating potato. The VNTl protein is not similar to any known allergens or toxins. The VNTl protein is expressed at low levels. The low hazard and low exposure minimizes risk associated with the VNTl protein.

       ii. Drinking water.

       Human exposure is not expected through drinking water.

        Non-dietary exposure.

 The VNTl 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 VNTl protein from diet, food, drinking water, or other occupational or residential use is negligible.

 Safety Determination

 U.S. population.

 The VNTl protein is unlikely to pose risk to human health. Study reports assessing the safety of the VNTl protein demonstrate a non-toxic mode of action for the VNTl protein, a history of safe use for homologous proteins in potato and tomato, and no

 significant sequence similarities between VNTI  and known allergens or toxins. The VNTl protein concentration was shown to be less than 100 ppb in tubers. Defining a tolerance limit for the VNTl protein is not practical considering the low expression and low exposure risk of the VNTl protein.

        Infants and children.

       The VNTl protein is unlikely to pose risk to infants or children.

 G. Effects on the Immune and Endocrine Systems

 The VNTI 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 VNTl protein in potato expires on December 31, 2015. An extension for the temporary tolerance is currently under review  (508375).

 I. International Tolerances

       None.
