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

**[\<]{.mark}EPA Biopesticides and Pollution Prevention Division
contact: \[insert name and telephone number with area
code\][\>]{.mark}**

**[\<]{.mark}*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.[\>]{.mark}**

**[\<]{.mark}*SUBMISSION:* E-mail the completed template to:
hollis.linda@epa.gov.[\>]{.mark}**

**[\<]{.mark}*TEMPLATE:*[\>]{.mark}**

**[\<]{.mark}\[Kaken Pharmaceutical Company, Ltd.\][\>]{.mark}**

**[\<]{.mark}\[Insert petition number\][\>]{.mark}**

[\<]{.mark} 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 **\[almonds, cucurbits, fruiting vegetables, ginseng, grapes,
pistachios, pome fruit, potatoes and strawberries\].**[\>]{.mark}

**[\<]{.mark}** 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.**[\>]{.mark}**

**[\<]{.mark}I. \[68173\] Petition Summary[\>]{.mark}**

> [\<]{.mark} **\[Insert petition number\]**[\>]{.mark}

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

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

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

**[\<]{.mark}** 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).**\][\>]{.mark}

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

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

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

**[\<]{.mark}** **\[1. [Acute Toxicity]{.underline}: Technical grade
polyoxin D zinc salt has very low acute toxicity. The acute oral LD~50~
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.[\>]{.mark}**

**2. [Subchronic Toxicity]{.underline}: 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]{.underline}: 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]{.underline}: 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.**\]

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

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

[\<]{.mark} i. *Food.* **\[Residues in/on crop commodities are estimated
to be negligible.\]**[\>]{.mark}

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

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

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

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

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

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

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

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

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

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

[\<]{.mark} **\[There are no current U.S. tolerances for polyoxin D zinc
salt or polyoxin D.\]**[\>]{.mark}

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

**[\<]{.mark} \[There are no current CODEX MRLs for polyoxin D zinc salt
or polyoxin D.\][\>]{.mark}**