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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: 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 Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 

346a(d), to amend 40 CFR part 174 to establish a temporary tolerance 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., Saint Louis, MO 63198 has submitted the following 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 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. Monsanto Petition Summary 

6G8453

A. Product Name and Proposed Use Practices

This notice of filing summarizes the information 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 material 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.
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B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. Cry51Aa2.834_16 protein was 

developed through limited modification 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 exemption 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 insecticidal mode-of-action that is well understood. Bt 

proteins have been used as safe and effective pest control agents in microbial formulations for 

many years. Numerous toxicology studies conducted with these 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 present in the midgut of target insects (OECD, 2007; Pigott and 

Ellar, 2007). These specific receptors have not been found in vertebrate taxa; therefore, Cry 

proteins derived from Bt are not expected to adversely affect mammals, and no adverse effects 

have been reported in mammals, birds, amphibians or reptiles (OECD, 2007; Schnepf, et al., 

1998).

The Cry51Aa2.834_16 protein does not share significant 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 pepsin. Data have been submitted demonstrating the lack of 

mammalian toxicity at high levels of exposure to purified Cry51Aa2 protein variants closely 

related to Cry51Aa2.834_16.

The genetic material encoding the Cry51Aa2.834_16 protein and the regulatory regions 

controlling expression are nucleic acids (DNA and 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 and RNA are in the category of 

substances generally recognized as safe (GRAS). EPA exempts nucleic acids that are part of a 

plant-incorporated protectant from the requirement of a tolerance (40 CFR 174.507). Data 

characterizing the genetic material necessary for the production of Cry51Aa2.834_16 in cotton
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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 conclusion that Cry51Aa2.834_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 human) exposure to the Cry51Aa2.834_16 protein.

D. Aggregate Exposure

1. Dietary exposure.

Cry51Aa2.834_16 is a plant-incorporated protectant in cotton, thus dietary exposure is 

deemed to be the most relevant route for assessing human risk. However, the primary product of 

cotton production is lint for textile use, and only highly refined cottonseed products (refined, 

bleached, and deodorized (RBD) oil and linters) are consumed by humans. The resulting 

processed cottonseed oil contains no detectable protein, while linters consist of nearly pure 

cellulose.

i. Food. Monsanto has considered available information 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 protein is present at low levels 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 essentially eliminates these 

exposure routes or reduces them to negligible levels. The use sites for the Cry51Aa2.834_16 

protein are agricultural for control of insects. Exposure to workers and bystanders resulting from 

plant pesticides will be negligible 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 toxicity potential for Cry51Aa2.834_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 certainty of no harm for the U.S. general population 

potentially exposed to the Cry51Aa2.834_16 protein.
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2. Infants and children. Non-dietary exposure to infants and children is not anticipated 

due to the patterns of use for these plant-incorporated protectants. The previously submitted data 

for the Cry51Aa2.834_16 protein provide no evidence of adverse effects that would warrant 

application of an additional safety factor for the 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 influence 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 protectant (PIP), Bacillus thuringiensis Cry51Aa2.834_16 

protein and genetic material necessary 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.