Monsanto Company CT273-16E1 Page 1 of 4 EPA BIOPESTICIDES AND POLLUTIO N PREVENTION DI VISION COMPANY

NOTICE OF FILING FOR PESTICIDE PE TITIONS PUBLISHED IN THE FEDERAL

REGISTER

EPA Biopesticides and Pollution Prevention Division contact: Ann Sibold, (703) 305-6502

Monsanto Company

6G8453
EPA has received a pesticide petition (6G8453) from Monsanto Company proposing,

pursuant to section 408(d) of the Federal F ood, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 174 to establish a temporary tole rance exemption for the plantpesticide Bacillus thuringiensis Cry51Aa2.834_16 protein in or on cotton.

Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, Monsanto Company, 800 North Lindbergh Blvd., Sa int Louis, MO 63198 has submitted the follo wing summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by Monsanto and EPA has not fully evaluated the me rits of the pesticide petition. The summary may have been edited by EPA if th e terminology used was unclear, the summary contained extraneous material, or the summary uni ntentionally made the read er conclude that the findings reflected EPA’s position an d not the position of the petitioner.

I. Monsanto Petition Summary

6G8453

A. Product Name and Proposed Use Practices

This notice of filing summarizes the info rmation submitted by Monsanto Company in support of a request for an exemption from the requirement of a tolerance for the Bacillus thuringiensis Cry51Aa2.834_16 protein and the genetic mate rial necessary for its production in cotton. Monsanto Company has developed biotechnology-derived cotton MON 88702 that protects against feeding damage caused by targeted hemipteran and thysanopteran insect pests. MON 88702 produces a modified insecticidal crystal (Cry) protein, Cry51Aa2.834_16, derived

from Bacillus thuringiensis

.Monsanto Company CT273-16E1 Page 2 of 4 B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. Cry51Aa2.834_16 protein was developed through limited modifi cation to the native Cry51Aa2 (TIC 807) protein identified

from Bacillus thuringiensis (Bt) (Baum, et al., 2012), and has greater than 97% sequence identity to native Cry51Aa2. The Cry51Aa2.834_16 protein has been incorporated to provide protection from feeding damage caused by targeted insect pests.

2. Magnitude of residues at the time of harvest and method used to determine the residue. A determination of the magnitude of residues at harvest is not required for residues that are exempt from tolerances.

3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. This petition is a temporary ex emption from the requirement of a tolerance without numerical limitation, thus an analytical detection method should not be required.

C. Mammalian Toxicological Profile

The Cry51Aa2.834_16 protein that is produced by MON 88702 was derived from the native Bt protein Cry51Aa2, and has an insectic idal mode-of-action that is well understood. Bt proteins have been used as safe and effective pe st control agents in microbial formulations for many years. Numerous toxicol ogy studies conducted with thes e microbial products show no significant adverse effects, and demonstrate that the Bt-derived products are nontoxic to

mammals.

The specificity of Bt Cry protein activity is determined by the mode-of-action, which includes binding to specific receptors pres ent in the midgut of target insects (OECD, 2007; Pigott and Ellar, 2007). These specific recep tors have not been found in ve rtebrate taxa; therefore, Cry proteins derived from Bt are not expected to adversely affect mammals, and no adverse effects have been reported in mammals, birds, amphibi ans or reptiles (OECD, 2007; Schnepf, et al., 1998). The Cry51Aa2.834_16 protein does not share sign ificant amino acid sequence similarity to known protein toxins or allergens, and is not derived from a source organism known to produce allergenic proteins. Furthermore, Cry51Aa2.834_16 has been shown to undergo rapid and complete degredation by pe psin. Data have been submitte d demonstrating the lack of mammalian toxicity at high levels of exposure to purified Cry51A a2 protein variants closely related to Cry51Aa2.834_16.

The genetic material enc oding the Cry51Aa2.834_16 protein a nd the regulatory regions controlling expression are nucleic acids (DNA an d RNA). DNA and RNA occur in all forms of plant and animal life and there is no documented instance of nucleic acids being associated with

toxic effects when consumed as a component of food. DNA a nd RNA are in th e category of substances generally recognized as safe (GRAS). EPA exempts nucle ic acids that are part of a plant-incorporated protectant from the requi rement of a tolerance (40 CFR 174.507). Data characterizing the genetic material necessary for the production of Cry51Aa2.834_16 in cottonMonsanto Company CT273-16E1 Page 3 of 4 were provided to the Agency. No mammalian toxicity is anticipated from dietary exposure to the genetic material necessary for production of the subject plant-incorporated protectant.

Collectively these data support a conclu sion that Cry51Aa2.83 4_16 protein will be nontoxic to humans and is unlikely to be a food allergen. There is reasonable certainty that no harm will result from mammalian (including huma n) exposure to the Cr y51Aa2.834_16 protein.

D. Aggregate Exposure

1. Dietary exposure. Cry51Aa2.834_16 is a plant-incor porated protectant in cott on, thus dietar y exposure is

deemed to be the most relevant route for assessing human risk. However, the primary product of cotton production is lint for text ile use, and only highly refine d cottonseed products (refined, bleached, and deodorized (RBD) oil and linte rs) are consumed by humans. The resulting processed cottonseed oil contains no detectable protein, while linters c onsist of nearly pure

cellulose.

i. Food. Monsanto has considered available info rmation on the aggregate exposure levels to consumers and major identifiable groups of consumers to the protein residue and related substances. A lack of significant similarity to mammalian toxins or allergens and rapid digestibility of the plant-incorporated protectant have been demonstrated.

ii. Drinking Water Exposure. Oral exposure from ingestion of drinking water is unlikely because the Cry51Aa2.834_16 prot ein is present at low le vels within the plant.

2. Non-dietary exposure

. Exposure via skin or inhalation is not likely because the plantincorporated protectants are contained within plant cells, which essent ially eliminates these exposure routes or reduces th em to negligible levels. Th e use sites for the Cry51Aa2.834_16 protein are agricultural for control of insects. Exposure to workers and bys tanders resulting from plant pesticides will be negligib le and unlikely to add measurably to any exposure resulting from

microbial or other Bacillus thuringiensis formulations. Exposure to infants and children via

residential or lawn use is not expected.

E. Cumulative Effects

There is no indication of mammalian toxic ity potential for Cry 51Aa2.834_16 protein.

Because there is no indication of mammalian toxicity to the plant-incorporated protectants there will be no opportunity for cumulative toxic effects.

F. Safety Determination

1. U.S. population. Sufficient data have been submitted to assess the health risk of Cry51Aa2.834_16 protein and the genetic material necessary for its production in cotton commodities. These data provide reasonable certain ty of no harm for the U.S. general population potentially exposed to the Cry51Aa2.834_16 protein.Monsanto Company CT273-16E1 Page 4 of 4 2. Infants and children

. Non-dietary exposure to infants and children is not anticipated due to the patterns of use for th ese plant-incorporated protectants . The previously submitted data for the Cry51Aa2.834_16 protein provide no evidence of adve rse effects that would warrant application of an additional safety factor for th e protection of infants and children. Furthermore, the provisions for consumption patterns, special susceptibility, and cumulative effects do not apply.

G. Effects on the Immune and Endocrine Systems

The available safety data for Cry51Aa2.834_16 protein indicate no adverse effects in mammals at high levels of exposure; thus, no effects on mammalian immune or endocrine systems are predicted. The lack of Cry51Aa2.834_16 homology to known toxins and allergens and the rapid degradation of Cry51Aa2.834_16 by pepsin suggests minimal risk for adverse effects on the immune system. Furthermore, the Cry51Aa2.834_16 protein is derived from B. thuringiensis

, which his known not to exert an in fluence on the endocrine system.

H. Existing Tolerances

Monsanto is requesting from EPA a temporary exemption from the requirement of a tolerance for the plant-incorporated protect ant (PIP), Bacillus thuringiensis Cry51Aa2.834_16 protein and genetic material neces sary for its production in cotton and in or on the food and feed

commodities of cotton.

I. International Tolerances

No Codex maximum residue levels exist for B. thuringiensis Cry51Aa2.834_16 protein in plants.