Document ID: EPA-HQ-OPP-2008-0417-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-07-31T04:00Z

<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: [insert
name and telephone number with area code]>

 

<INSTRUCTIONS:  Please utilize this outline in preparing the pesticide
petition.  In cases where the outline element does not apply, please
insert “NA-Remove” and maintain the outline. Please do not change
the margins, font, or format in your pesticide petition. Simply replace
the instructions that appear in green, i.e., “[insert company
name],” with the information specific to your action.>

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

<TEMPLATE:>

<[Kaken Pharmaceutical Company, Ltd.]>

<[Insert petition number]>

<	EPA has received a pesticide petition ([insert petition number]) from
[Arysta LifeScience North America, Agent for Kaken Pharmaceutical
Company, Ltd.], [15401 Weston Parkway, Suite 150, Cary, NC 27513]
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
biochemical pesticide [Polyoxin D zinc salt] in or on [almonds,
cucurbits, fruiting vegetables, ginseng, grapes, pistachios, pome fruit,
potatoes and strawberries].>

<	Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, [Kaken
Pharmaceutical Company, Ltd.] has submitted the following summary of
information, data, and arguments in support of their pesticide petition.
This summary was prepared by [Arysta LifeScience North America,] 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. [68173]  Petition Summary>

<	[Insert petition number]>

<A. Product Name and Proposed Use Practices>

<	[Polyoxin D zinc salt is the active ingredient in ENDORSE® Water
Dispersible Granules which is proposed for use to control fungal
diseases of almonds, cucurbits, fruiting vegetables, ginseng, grapes,
pistachios, pome fruit, potatoes and strawberries.  The active portion
of polyoxin D zinc salt is polyoxin D which is produced by a bacterium
that is naturally occurring in the soil.  Polyoxin D inhibits the growth
of phytopathogenic fungal cell wall chitin by competitively inhibiting
chitin synthetase.  Without chitin, susceptible fungi are unable to
continue growing and infecting plant cells.  Polyoxin does not kill the
fungi; it simply stops the fungal growth.  The action of Polyoxin D is
highly specific; it does not affect bacteria, viruses, or mammals.]>

<B. Product Identity/Chemistry>

<	1. Identity of the pesticide and corresponding residues. [The CAS name
for polyoxin D zinc salt is zinc
5-[[2-amino-5-O-(aminocarbonyl)-2-deoxy-L-xylonoyl]amino]-1-(5-carboxy-3
,4-dihydro-2,4-dioxo-1(2H)-pyrimidyl)-1,5-dideoxy-β-D-allofuranuronate)
.]>

<	2. Magnitude of residues at the time of harvest and method used to
determine the residue. [For each of the crops, the proposed use rate is
0.7 oz AI/acre which is equivalent to 0.004 lb AI/acre.  At this very
low use rate, only negligible residues are anticipated to be present
in/on the harvested raw agricultural commodities.]>

<	3. A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. [A tolerance
exemption is proposed.  Therefore, no tolerance enforcement method is
proposed.]>

<C. Mammalian Toxicological Profile>

<	[1. Acute Toxicity: Technical grade polyoxin D zinc salt has very low
acute toxicity.  The acute oral LD50 was determined to be greater than
10,000 mg/kg in rats.  At the highest dose tested (800 mg TGAI/kg/day)
in a teratology study in rabbits, body weight reduction was observed in
the dams while no adverse effects were observed in the pups.  Also, no
statistically significant adverse effects in the offspring were observed
in a 2-generation reproduction study at dietary intake levels greater
than 10,000 mg TGAI.>

2.  Subchronic Toxicity: Technical grade polyoxin D zinc salt has very
low subchronic toxicity.  For 90 days, rats were fed a diet containing
up to 20,000 ppm technical grade polyoxin D zinc salt.  The NOAEL was
determined to be 2000 ppm (119 mg TGAI/kg bw/day in males and 135 mg
TGAI/kg bw/day in females).  At 20,000 ppm, decreased body weight gain
and decreased food consumption were observed.  In a 28-day study to
evaluate immunotoxicity, female mice were fed a diet containing up to
40,000 ppm technical grade polyoxin D zinc salt, and no adverse effects
were observed.  The NOAEL was determined to be approximately 8000 mg
TGAI/kg/day.

3.  Chronic Toxicity: Technical grade polyoxin D zinc salt has very low
chronic toxicity.  For 24 months, rats were fed a diet containing up to
5% technical grade polyoxin D zinc salt and evaluated for toxicity,
including oncogenicity.  No statistically significant adverse effects
were observed at the highest dose tested.  The NOAEL was determined to
be 2,058.7 mg TGAI/kg bw/day in males and 2,469.8 mg TGAI/kg bw/day in
females.

4. Mutagenicity: Based upon the weight of evidence, technical grade
polyoxin D zinc salt is not mutagenic.  Technical grade polyoxin D zinc
salt was determined to be non-mutagenic in an Ames test, a Rec-assay
with Bacillus subtilis H-17 and M-45, and a host-mediated assay with S.
typhimurium G-46 in mice.  Equivocal results were obtained in a
chromosome aberration study, and data indicating weak mutagenicity were
obtained in a second Ames study. However, in vivo (whole animal) studies
indicate that technical grade polyoxin D zinc is not mutagenic. 
Technical grade polyoxin D zinc was determined to be not mutagenic at
the highest dose tested (2000 mg TGAI/kg) in the mouse micronucleus
test.  Most importantly, technical grade polyoxin D zinc salt is not
teratogenic and not oncogenic.  These results are consistent with a
non-mutagenic material.]

<D. Aggregate Exposure>

<	1. Dietary exposure. [Due to the very low proposed use rate on crops,
dietary exposure to polyoxin D and to polyoxin D zinc salt is
anticipated to be very low.]>

<	i. Food. [Residues in/on crop commodities are estimated to be
negligible.]>

<	ii. Drinking water. [Polyoxin D zinc salt is registered to control
fungal diseases in turf.  The use on turf was previously estimated to
result in very low risk from drinking water exposure.  The proposed
additional use on selected crops at very low use rates is estimated to
result in very low drinking water exposure to polyoxin D zinc salt and
to polyoxin D via drinking water.]>

<	2. Non-dietary exposure. [Polyoxin D zinc salt is registered to
control fungal diseases in turf.  The use on turf was previously
estimated to result in very low non-dietary risk, including from
hand-to-mouth exposure to infants and children.]>

<E. Cumulative Effects>

<	[Polyoxin D zinc salt has very low mammalian toxicity. It is not known
to share a toxicological mode of action with any other pesticide.]>

<F. Safety Determination>

<	1. U.S. population. [Based upon the combination of very low mammalian
toxicity and the very low aggregate exposure, the combination of the
registered turf use and the proposed crop uses of  polyoxin D zinc salt
has a reasonable certainty of no harm to the U.S. population.]>

<	2. Infants and children. [The available data indicate that polyoxin D
zinc salt has very low toxicity, including to infants and children.  No
increased sensitivity of infants or children was indicated in any of the
laboratory studies.  Therefore, the combination of the registered turf
use and the proposed crop uses of polyoxin D zinc salt has a reasonable
certainty of no harm to infants and children.]>

<G. Effects on the Immune and Endocrine Systems>

<	[In a 28-day study to evaluate immunotoxicity (splenic antibody
study), female mice were fed a diet containing up to 40,000 ppm
technical grade polyoxin D zinc salt, and no adverse effects were
observed.  The NOAEL was determined to be approximately 8000 mg TGAI/kg
bw/day.  No evidence of endocrine system effects was observed in the
subchronic, chronic, teratology or reproduction studies. ]>

<H. Existing Tolerances>

<	[There are no current U.S. tolerances for polyoxin D zinc salt or
polyoxin D.]>

<I. International Tolerances>

<	[There are no current CODEX MRLs for polyoxin D zinc salt or polyoxin
D.]>

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