FILE NAME:  biopetit.wpt   (1/1/2005) (xml)

Number: P4

ATTENTION: 

All commodity terms must comply with the Food and Feed Commodity
Vocabulary database (http://www.epa.gov/pesticides/foodfeed/).

                All text in blue font (instructions for preparing the
document), should be removed prior to sending the document to the
Federal Register Staff.  Instructional text and prompts in green font
should also be removed.

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

(1/1/2005)

EPA Biopesticides and Pollution Prevention Division contact: [insert
name and telephone number with area code]

INSTRUCTIONS: Use this template in preparing your notice of filing for
your company’s pesticide petition.  In cases where the outline element
does not apply,  insert “NA-Remove” and maintain the outline.  The
comment balloons appearing in the left margin contain Government
Printing Office (GPO) typesetting codes which expedite the Federal
Register (FR) publication process at EPA for the FR document containing
your company’s pesticide petition. In the template, do not remove or
alter the comment balloons; change the margins, font, or format; or use
the WordPerfect comment function.  Follow the instructions that appear
italicized, color coded, and bracketed. 

SUBMISSION: E-mail the completed template to: hollis.linda@epa.gov.

TEMPLATE:

Bayer CropScience LP

	EPA has received a pesticide petition [insert petition number] from
Bayer CropScience LP, 2 T.W. Alexander Dr. Research Triangle Park, NC
27709, 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 exemption from the requirement of a tolerance for the
plant-pesticide Cry2Ae in or on all plants

    The petitioner’s summary of the pesticide petition is printed
below as required by section 408(d) (3) of the Federal Food Drug and
Cosmetic Act.  The summary of the petition was prepared by Bayer
CropScience and represents the view of the petitioner.  The petition
summary announces the availability of a description of the analytical
methods available to the EPA for the detection and measurement of the
pesticide chemical residues or an explanation of why no such method is
needed.

This notice of filing summarizes the information submitted and cited by
Bayer CropScience LP in support of a request for a temporary exemption
from the requirement of a tolerance for the Bacillus thuringiensis
Cry2Ae protein and the genetic material necessary for its production in
cotton.  

.  The Bacillus thuringiensis Cry2Ae protein has been incorporated into
cotton plants to provide control of lepidopteran insect pests such as
cotton bollworm and tobacco budworm.  Cry2Ae transformed plants are
derived from transformation events GHB714 and GHB119 that contain the
Cry2Ae protein via Agrobacterium mediated transformation.  The Cry2Ae
protein is highly specific to the targeted lepidopteran species, and is
non-toxic to mammalian species.  The Cry2Ae technology provides
producers with efficacious control of lepidopteran pest species in a
safe and efficient manner.

.   No analytical method is included because this petition requests a
temporary exemption from the requirement for a tolerance.

	Bacillus thuringiensis proteins have been used as safe and effective
pest control agents in microbial formulations for almost 40 years. 
There have been over 150 registered microbial Bacillus 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
from the requirement of a tolerance has been in place for these products
since at least 1971 (40 CFR 180.1011).

	Toxicology studies conducted to determine the toxicity of the Cry2Ae
protein demonstrated that the protein is not toxic to mammals.  In an
acute toxicity study in mice, high doses of Cry2Ae protein revealed no
adverse effects.  In an in vitro study, the Cry2Ae protein was rapidly
and completely degraded in simulated gastric fluid in the presence of
pepsin at pH 1.2 with no residual protein visible after 2 minutes of
incubation.  This indicates that the protein is highly susceptible to
digestion in the human digestive tract and that the potential for
adverse health effects from acute or chronic exposure is virtually
nonexistent. 

	Proteins in general are not known to be chronic toxicants or
carcinogens. A search of relevant databases indicated that the amino
acid sequence of the Cry2Ae protein exhibits no significant homology to
the sequences of known protein toxins.  In addition, there was no
homology with sequences of known allergens and Cry2Ae was not
glycosylated in planta.  Therefore, the Cry2Ae protein is highly
unlikely to exhibit an allergic response.

	The genetic material necessary for the production of the Cry2Ae protein
are nucleic acids (DNA) which are common to all forms of plant and
animal life. There are no known instances of where nucleic acids have
caused toxic effects as a result of dietary exposure.

	Collectively, the available data on the Cry2Ae protein along with a
proven safe use of microbial Bacillus thuringiensis products establishes
the safety of the Cry2Ae protein and the genetic material necessary for
its production in all plants.

	Bacillus thuringiensis proteins are known to have a high degree of
insect specificity to lepidopteran species via binding to specific
receptors in the insect gut.  There are no receptors for these proteins
in mammalian species and therefore, these proteins are not toxic to
humans, wildlife, or beneficial insects, and readily break down in the
acidic environment of the digestive system.  The level of Cry2Ae protein
expressed in planta is very low, and is contained within the plant
making any route of exposure other than ingestion very unlikely.  While
dietary exposures may occur at low levels through consumption of raw
agricultural commodities, significant exposure to the Cry2Ae protein is
unlikely.  Since the Cry2Ae protein is contained within the plant
structure, it is highly unlikely that there would be opportunity for the
Cry2Ae protein to be introduced to drinking water or through physical or
other forms of contact in which a traditional pesticide may be
introduced into the body.  In summary, the potential for aggregate
exposure to the Cry2Ae protein is highly unlikely.

  

	Common modes of toxicity are not relevant to consideration of the
cumulative exposure to the Cry2Ae protein.  The Cry2Ae protein readily
breaks down during digestion, and has demonstrated a lack of mammalian
toxicity.  Furthermore, Bacillus thuringiensis proteins are known to
have very specific modes of action which do not affect humans, such that
the biological effects of the Cry2Ae protein do not appear to be
cumulative with any other known compounds.

 								

. Considering the minute quantities of protein expressed within the
plant, the non-toxic nature of the Cry2Ae protein and Bacillus
thuringiensis proteins in general, the high degree of digestibility, the
lack of non-dietary exposure, and the lack of allergenic potential, BCS
concludes that the risk posed by Cry2Ae protein to the U.S. population
is insignificant.

.  Non-dietary exposure to infants and children is not anticipated, due
to the proposed use pattern of the Cry2Ae protein.  Due to the lack of
toxicity of the product on mammals, the lack of allergenic potential,
and the high degree of digestibility of the Cry2Ae protein, it is not
anticipated to pose any harm to infants and children from dietary
exposure.

  

Cry2Ae is a pesticidal protein derived from a source not known to exert
an influence on the immune or endocrine system.  Given the
characteristics of the Cry2Ae protein as described above, the potential
for effects on the immune or endocrine systems is highly unlikely. 

There are no existing tolerances or exemptions from the requirement of a
tolerance for the Cry2Ae protein granted to Bayer CropScience.

 

	No maximum residue levels have been established for the Cry2Ae protein
under the Codex Alimentarius.

	 

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