[\<]{.mark}EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY
NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL
REGISTER

(7/1/2007)[\>]{.mark}

[\<]{.mark}EPA Biopesticides and Pollution Prevention Division contact:
Shanaz Bacchus, (703) 308-8097.[\>]{.mark}

[\<\>]{.mark}

[\<]{.mark}TEMPLATE: Company submission[\>]{.mark}

[\<]{.mark}Circle One Global, Inc.[\>]{.mark}

[\<]{.mark}Pesticide Petition 7F7302[\>]{.mark}

[\<]{.mark} EPA has received a pesticide petition 7F7302 from Circle One
Global, Inc. (Circle One), P.O. Box 28, Shellman, GA 39886-0028,
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 180.1254
to establish an amendment/expansion of an existing tolerance exemption
for the microbial pesticide *Aspergillus flavus* NRRL 21882 for its use
on the food/feed commodity corn.[\>]{.mark}

[\<]{.mark} Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended,
Circle One has submitted the following summary of information, data, and
arguments in support of their pesticide petition. This summary was
prepared by Circle One 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.[\>]{.mark}

[\<]{.mark}I. Circle One Petition Summary[\>]{.mark}

> [\<]{.mark} Pesticide Petition 7F7302[\>]{.mark}

[\<]{.mark}A. Product Name and Proposed Use Practices[\>]{.mark}

[\<]{.mark} Circle One proposes to expand the registration for
afla-guard^®^, which is formulated with *Aspergillus flavus* NRRL 21882,
to include use on corn. The product will be applied aerially at 20
pounds per acre, the rate currently approved for use on peanuts. The
application to corn will be once per season at the first sign of corn
tasseling.[\>]{.mark}

[\<]{.mark}B. Product Identity/Chemistry[\>]{.mark}

[\<]{.mark} 1. Identity of the pesticide and corresponding residues.
*Aspergillus flavus* NRRL 21882 is a naturally-occurring
non-aflatoxin-producing fungal active ingredient that will be used to
displace the ubiquitous *A. flavus* group of microbes, many of which can
produce aflatoxins, which are potent carcinogens. The residues resulting
from treatment on corn are *Aspergillus flavus* NRRL 21882. The active
ingredient is cultured from spores originally obtained from the U.S.
Department of Agriculture's (USDA) Agricultural Research Service (ARS)
Patent Culture Collection in Peoria, Illinois. It is cultured on a
selective isolation medium and can be identified by vegetative
compatibility group (VCG) assays and characterized as
non-aflatoxin-producing by standard thin layer chromatography (TLC) and
high performance liquid chromatography (HPLC) procedures. Product
characterization previously submitted confirmed the absence of
aflatoxins (B1, B2, G1, and G2), and cyclopiazonic acid (CPA) (see
*Aspergillus flavus* NRRL 21882 Biopesticides Registration Action
Document (BRAD), May 24, 2004, pp. 15-16). Additionally, the
manufacturer of the technical grade active ingredient routinely conducts
standard microbiological assays on *Aspergillus flavus* NRRL 21882
conidia to assay for potential aflatoxins, metabolites, CPA, bacterial
contaminants, and bacterial pathogens. [\>]{.mark}

[\<]{.mark} 2. Magnitude of residues at the time of harvest and method
used to determine the residue. It is expected that the percent toxic
strains of total *A. flavus* found in corn grain will be reduced as a
result of treatment with the registered product. A dilution plating
method has been used to quantify the *A. flavus* colonization in both
corn and peanuts, as well as the aflatoxin contamination (J.W. Dorner
(2002) Simultaneous Quantification of *Aspergillus flavus/A.
parasiticus* and Aflatoxins in Peanuts, J. of AOAC International, 85(4):
911-916).[\>]{.mark}

[\<]{.mark} 3. A statement of why an analytical method of detecting and
measuring the levels of the pesticide residue are not needed. A petition
for exemption from the requirement of tolerance is being submitted with
applications to add the corn use to both the manufacturing-use label for
*Aspergillus flavus* NRRL 21882 and the end-use label for afla-guard^®^.
EPA previously has determined that an exemption from tolerance is
supported when the product is used on peanuts (see 69 FR 39341, June 30,
2004, codified at 40 C.F.R. § 180.1254) and temporarily when used on
corn (see 72 FR 27460, May 16, 2007) in association with an Experimental
Use Permit (EPA File Symbol 75624-EUP-2). In reaching these conclusions,
EPA noted that *Aspergillus flavus* NRRL 21882 occurs naturally in the
environment and beneficially displaces toxigenic strains of
naturally-occurring *A. flavus*. EPA also noted that there is no
indication of toxicity, infectivity, or pathogenicity in mammalian acute
oral and pulmonary studies using *Aspergillus flavus* NRRL 21882 as the
test material. Accordingly, a numerical tolerance and an analytical
method to measure pesticide residues are not needed.[\>]{.mark}

[\<]{.mark}C. Mammalian Toxicological Profile[\>]{.mark}

[\<]{.mark} The toxicological profile previously has been summarized and
published in the final rule to create a tolerance exemption for use on
peanuts, 69 Fed. Reg. 39341 (Jun. 30, 2004) as well as in the May 24,
2004, BRAD.[\>]{.mark} The pesticide is classified as Toxicity Category
IV on the basis of acute oral toxicity/pathogenicity tests submitted for
the exemption from tolerance for its use on peanuts. EPA also noted that
there is no indication of toxicity, infectivity, or pathogenicity in
mammalian acute oral, pulmonary and intravenous studies using
*Aspergillus flavus* NRRL 21882 as the test material. *Aspergillus
flavus* NRRL 21882 cleared all tissues examined during those tests (see
69 FR 39341, June 30, 2004). Those studies also supported the temporary
exemption from tolerance for corn (see 72 FR 27460, May 16, 2007).

[\<]{.mark}D. Aggregate Exposure[\>]{.mark}

[\<]{.mark} 1. Dietary exposure. The total dietary exposure consists of
the potential exposure in food and drinking water, which are discussed
below. *Aspergillus flavus* NRRL 21882 is neither toxic nor infective as
determined by submitted studies (see May 24, 2004, BRAD). A tolerance
exemption has been granted for use on peanuts (69 Fed. Reg. 39341, Jun.
30, 2004). [\>]{.mark}

[\<]{.mark} i. Food. The product is proposed for use for treatment of
corn at the same rate as approved for use on peanuts. Levels of
*Aspergillus flavus* NRRL 21882 are not expected to exceed total levels
of naturally-occurring Aspergillus fungi on corn and thus would not
increase dietary exposure. *Aspergillus flavus* NRRL 21882 is a
naturally-occurring strain that does not produce aflatoxins, CPA, or
other known intermediates in the aflatoxin biosynthetic pathway, some of
which are toxic. The use of the product reduces the aflatoxin content of
treated corn when compared with untreated controls, as demonstrated by
efficacy data submitted with the registration amendment application for
afla-guard^®^. In the United States, aflatoxin levels in corn are
monitored to verify they do not exceed the regulatory action levels
(limits) set by the U.S. Food and Drug Administration (FDA). [\>]{.mark}

[\<]{.mark} ii. Drinking water. Exposure to *Aspergillus flavus* NRRL
21882 in drinking water is not expected to be greater than existing
exposures to *A. flavus* strains generally. Potential risks via exposure
to drinking water or runoff are mitigated adequately by, among other
things, percolation through soil. The product is not applied to crops
grown in water and is not likely to accumulate in drinking water if used
as directed on the label. Accordingly, exposure by drinking water will
not increase as a result of the proposed use on corn.[\>]{.mark}

[\<]{.mark} 2. Non-dietary exposure. The product currently is registered
for use on peanuts only. EPA has evaluated occupational, residential,
ecological, and environmental exposure with the peanut use. Based on
these evaluations, the only mitigation required was with respect to the
exposure by pesticide handlers. To mitigate this exposure, EPA requires
the use of personal protective equipment. This requirement is triggered
by the properties of the *A. flavus* species, not the specific
registered strain, which has had no hypersensitivity incidents reported
during the 12 years handled by workers in the laboratory and in field
trials. There are no residential or non-crop uses. Non-occupational
exposure is not likely to be greater than that which normally exists to
the naturally-occurring *A. flavus* species. This issue is discussed in
further detail at 69 FR 39347 and in the May 24, 2004, BRAD.[\>]{.mark}

[\<]{.mark}E. Cumulative Effects[\>]{.mark}

[\<]{.mark} Completed toxicology studies indicate that *Aspergillus
flavus* NRRL 21882 is not toxic or pathogenic to humans. It currently is
registered for use on peanuts only. Another strain of *Aspergillus
flavus, A. flavus* AF36, is registered under Section 3(c)(5) for use on
cotton. *A. flavus* AF36 is also temporarily exempt from the requirement
of a tolerance on corn in accordance with an EUP (EPA File Symbol
71693-EUP-2). Other *A. flavus* strains abound naturally in the
environment. The displacement of aflatoxin-producing strains of *A.
flavus* by *Aspergillus flavus* NRRL 21882 is expected to reduce
aflatoxin contamination in corn, as demonstrated by the efficacy data
submitted with the registration amendment for afla-guard^®^. As
*Aspergillus flavus* NRRL 21882 is naturally occurring, in toxicity
Category IV, and atoxigenic, no cumulative incremental effect from its
use on corn is expected.[\>]{.mark}

[\<]{.mark}F. Safety Determination[\>]{.mark}

[\<]{.mark} 1. U.S. population. There is a reasonable certainty that no
harm will result to the U.S. population from aggregate exposures to
residues of *Aspergillus flavus* NRRL 21882 as a result of its use on
corn. EPA has already concluded that the organism is non-toxic and
non-pathogenic to animals and humans. The additional exposure to this
organism from use on corn should not increase the overall exposure to
*A. flavus*, and the use is expected to reduce potential exposure to
potent mycotoxins. Accordingly, use of the product on corn should not
change the conclusion concerning the safety of the product already
reached by EPA in the context of its use on peanuts.[\>]{.mark}

[\<]{.mark} 2. Infants and children. EPA previously has concluded that
*Aspergillus flavus* NRRL 21882 is non-toxic to mammals, including human
infants and children. As there are no threshold effects of concern for
infants, children, and adults, no additional margin of safety was added
in EPA's assessment of the product's use on peanuts. As *Aspergillus
flavus* NRRL 21882 is naturally occurring, in toxicity Category IV, and
atoxigenic, it can be concluded that no additional safety factor is
needed.[\>]{.mark}

[\<]{.mark}G. Effects on the Immune and Endocrine Systems[\>]{.mark}

[\<]{.mark} EPA has not required submission of information on the
endocrine effects of the active ingredient, *Aspergillus flavus* NRRL
21882. There is no known metabolite produced by this microorganism that
acts as an endocrine disruptor. The submitted toxicity/infectivity
and/or pathogenicity studies in the rodent indicate that, following oral
and pulmonary routes of exposure, the immune system is intact and able
to process and clear the active ingredient. Additionally, based on the
low potential exposure associated with the proposed, single application
per season use, no adverse effects to the endocrine or immune system are
expected. [\>]{.mark}

[\<]{.mark}H. Existing Tolerances[\>]{.mark}

[\<]{.mark} An exemption from the requirement of a tolerance currently
exists for residues of *Aspergillus flavus* NRRL 21882 in/on peanuts,
which is published in 40 C.F.R. § 180.1254. There also is a temporary
tolerance exemption for residues of *Aspergillus flavus* NRRL 21882
in/on corn when used in accordance with Experimental Use Permit
75624-EUP-2, which will expire on May 2, 2009.[\>]{.mark}

[\<]{.mark}I. International Tolerances[\>]{.mark}

[\<]{.mark} There is no Codex maximum residue level for residues of
*Aspergillus flavus* NRRL 21882.[\>]{.mark}