**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER**

**EPA Registration Division contact: \[Philip V. Errico (7505C) - Office
of Pesticide Programs-U.S. Environmental Protection Agency- S7723,
Office of Pesticide Programs, One Potomac Yard, 2777 S. Crystal Dr.,
Arlington, VA 22202-Phone: 703-305-6663 - Email:
errico.philip@epamail.epa.gov.\]**

***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.**

***TEMPLATE:***

**\[Dow AgroSciences, LLC\]**

**\[Insert petition number\]**

EPA has received a pesticide petition **(PP# 8F7369)** from **\[Dow
AgroSciences, LLC.\], \[9330 Zionsville Road, Indianapolis, Indiana
46268\]** 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.

**(Options (pick one)**

> 1\. by establishing a tolerance for residues of

~~2. to establish an exemption from the requirement of a tolerance for~~

**\[penoxsulam\] in or on the raw agricultural commodity \[nut, tree,
group 14\] at \[0.01\] parts per million (ppm), \[grape\] at \[0.01\]
parts per million (ppm), \[almond, hulls\] at \[0.01\] parts per million
(ppm), \[pistachio\] at \[0.01\] parts per million (ppm). EPA has
determined that the petition contains data or information regarding the
elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not
fully evaluated the sufficiency of the submitted data at this time or
whether the data supports granting of the petition. Additional data may
be needed before EPA rules on the petition.**

*A. Residue Chemistry*

**1.** *Plant metabolism.* **\[**Based on results of the metabolism
studies in plants that are summarized below, it is concluded that the
residue definition in plants is the parent compound alone, penoxsulam.

A nature of residue study (NOR) was conducted in grapes using a soil
application of penoxsulam. Penoxsulam, ^14^C-labeled either in the
2-position on the triazolopyrimidine ring (TP) or uniformly labeled in
the phenyl-ring (Ph), was applied as a broadcast spray onto soil around
established grape vines at a single application rate of approximately 20
g a.i./ha. The soil in this study was a sandy clay loam. Application was
made when grapes vines were at growth stage BBCH 55 (early flowering).
After application, the plots were irrigated with 1 cm of water daily for
7 days. Grapes and leaves were harvested at 118 days after application.

Mature grapes contained residues below the limit of quantification
(0.0008 µg/g penoxsulam equivalents). The PH-label and TP-label leaves
collected at maturity contained 0.016 µg/g and 0.013 µg/g penoxsulam
equivalents, respectively. In the mature leaves, approximately 65% of
the leaf TRR was extractable with neutral solvent, of which
approximately half partitioned into organic solvent. The majority of the
organic phase was identified as numerous low-level metabolites, while
the aqueous phase consisted of primarily polar, solvent-front residues.
The residue was characterized as low-level degradates, tentatively
including the 5-hydroxy-penoxsulam and the dihydroxy-penoxsulam
metabolites.

In summary, very low levels of soil-applied penoxsulam and degradates
are taken up by the vine. No penoxsulam was detected in the leaves, and
due to the low TRR levels in the grapes, no penoxsulam is predicted
there either. The residue was characterized as low-level degradates,
tentatively including the 5-hydroxy-penoxsulam and the
dihydroxy-penoxsulam metabolites.

The nature of residue study in rice, treated with ^14^C-labeled
penoxsulam (2-position on the triazolopyrimidine ring or uniformly
labeled in the phenyl ring) at 100 g/ha, demonstrated that no
significant residues (0.003-0.022 ppm) were found in mature straw and
grain. The residues were fractionated by reversed-phase HPLC and
consisted of penoxsulam, 5-OH penoxsulam (identified by retention time),
and two unidentified peaks. Each component was \<0.01 μg/g (penoxsulam
equivalents). Based on the plant metabolism studies, the tolerance
expression is the parent, penoxsulam.

Metabolism studies in livestock animals with ^14^C-labeled penoxsulam
(2-position on the triazolopyrimidine ring or uniformly labeled in the
phenyl ring) at a concentration equivalent to about 10 ppm in the diet
indicated that approximately 99% of the administered dose was eliminated
in the excreta. The low levels of residues (0.002-0.07 ppm) in fat and
edible tissues, milk or eggs demonstrate that residues due to penoxsulam
would not accumulate in the animals. Additionally, the dose levels in
these studies are about 200 to 1000 times higher than the theoretical
maximum exposure in the animal diet of rice commodities treated with
penoxsulam, therefore, livestock feeding studies are not considered
necessary. **\]**

**2. *Analytical method.* \[**In the Magnitude of Residue (MOR) studies
conducted in grapes, almonds and pecans to support tolerances proposed
in this petition, residues of penoxsulam were determined using the
analytical method GRM 04.09. Residues of penoxsulam were extracted from
the crop samples by homogenizing and shaking with an acetonitrile/water
solution (80:20 v/v). An aliquot was diluted with 0.1N HCl and purified
using a 96-well polymeric-reverse phase extraction (SPE) plate. The SPE
plate was washed with a 40/60 methanol/water solution and eluted with
acetonitrile into a 96-well plate containing an
acetonitrile/methanol/water mobile phase (15:15:70 containing 0.1%
acetic acid) and a stable isotope internal standard. The final solution
was analyzed by liquid chromatography with positive-ion electrospray
tandem mass spectrometry (LC/MS/MS). The limit of detection (LOD) and
limit of quantitation (LOQ) are 0.003 µg/g and 0.010 µg/g,
respectively.**\]**

**3. *Magnitude of residues.* \[**The proposed tolerances (Section F)
are supported by MOR studies in grapes, almonds and pecans conducted in
the U.S. Trials were conducted in almonds and pecans to support a
tolerance for the nut tree crop group (Nuts, tree, group 14) including
pistachios, and almond hulls. Additionally, trials were conducted in
grapes to support a tolerance for grapes.

Based on the properties of penoxsulam and results from residue studies
in other crops along with the proposed use pattern on tree nuts and
grapes, Dow AgroSciences expected that residues in almond hulls, nutmeat
and grapes would not be detected. A proposal for was submitted to US EPA
that suggested almond and pecan trials be carried out at three locations
and grape trials would be carried out at four locations. The objective
of these trials would be to confirm that penoxsulam residues in almond
hulls, nutmeat and grapes are not detected when penoxsulam is applied
according to the proposed use patterns.

#### Grape -- Magnitude of Residue Trials and Processing Study

The magnitude of residues of in grapes was determined following two
applications of penoxsulam. Four trials were conducted at sites in New
York, California and Washington (NAFTA zones 1, 10 and 11,
respectively). was applied to the vineyard floor as the formulation (an
) in each of two broadcast applications with a 60 day PHI. The target
rates for the first and second applications were penoxsulam at 40 g
a.i./ha (0.0357 lb ai/A) and 20 g a.i./ha (0.0178 lb ai/A),
respectively. Additionally, at one trial site a plot was treated with
penoxsulam at a 5X rate (200 g ai/ha + 100 g ai/ha, or 0.1784 lb ai/A +
0.0892 lb ai/A) and grapes were collected for processing to grape juice
and raisins. All spray mixtures included crop oil concentrate at 1.25%
(v/v).

Penoxsulam was determined using liquid chromatography with positive-ion
electrospray tandem mass spectrometry (LC/MS/MS). The limit of detection
(LOD) and limit of quantitation (LOQ) for penoxsulam in grapes, juice
and raisins were 0.003 µg/g and 0.01 µg/g, respectively.

Residue was not detected (ND, \<0.003 µg/g) in any of the grape samples
from treated or untreated control plots. Additionally, no residue was
detected in whole grapes collected in the field from the 5X rate
treatment or at the beginning of processing, and no residue was detected
in the grape juice or raisins produced from processing these grapes.
Therefore, there is no concentration of residue from grapes to either
juice or raisins.

#### Almond -- Magnitude of Residue Trials

The magnitude of residues of in almond hulls and nutmeat was determined
following two applications of penoxsulam. Three trials were conducted at
sites in California (NAFTA zone 10). was applied to the orchard floor as
the formulation (an ) in each of two broadcast applications with a 60
day PHI. The target rates for the first and second applications were 50
g a.i./ha (0.0446 lb ai/A) and 20 g a.i./ha (0.0178 lb ai/A),
respectively. All spray mixtures included crop oil concentrate at 1.25%
(v/v).

Penoxsulam was determined using liquid chromatography with positive-ion
electrospray tandem mass spectrometry (LC/MS/MS). The limit of detection
(LOD) and limit of quantitation (LOQ) for penoxsulam in both almond
hulls and nutmeat were 0.003 µg/g and 0.01 µg/g, respectively. Residue
was not detected (ND, \<0.003 µg/g) in any of the almond hull or nutmeat
samples.

#### Pecan -- Magnitude of Residue Studies

The magnitude of residues of in was determined following two
applications of penoxsulam. Three trials were conducted at sites in
Georgia, Louisiana and Texas (NAFTA zones 2, 4 and 8). was applied to
the orchard floor as the formulation (an ) in each of two broadcast
applications with a 60 day PHI. The target rates for the first and
second treatment applications were 50 g a.i./ha (0.0446 lb ai/A) and 20
g a.i./ha (0.0178 lb ai/A), respectively. All spray mixtures included
crop oil concentrate at 1.25% (v/v).

Penoxsulam was determined using liquid chromatography with positive-ion
electrospray tandem mass spectrometry (LC/MS/MS). The limit of detection
(LOD) and limit of quantitation (LOQ) for penoxsulam in pecan nutmeat
were 0.003 µg/g and 0.01 µg/g, respectively. Residue was not detected
(ND, \<0.003 µg/g) in any of the pecan nutmeat samples from control or
treated plots.

***B. Toxicological Profile***

**1. *Acute toxicity.* \[**The acute toxicity of penoxsulam is
considered low. The acute oral and dermal LD~50~s were greater than 5000
mg/kg, while the acute inhalation LC~50~ was greater than the highest
attainable aerosol concentration (3.50 mg/L). Only very slight,
transient dermal irritation was seen, and mild eye irritation was noted.
Penoxsulam was negative for skin sensitization in a Magnussen and
Kligman maximization test involving intradermal injection of penoxsulam
with an adjuvant**.\]**

**2. *Genotoxicity.* \[**Penoxsulam was negative for genotoxicity when
tested in *in vitro* and *in vivo* systems**.\]**

**3. *Reproductive and developmental toxicity.* \[**Penoxsulam did not
have any effect on reproductive parameters at dose levels that induced
treatment-related effects in parental rats. At the highest dosage tested
(300 mg/kg/day), body weights and weight gains in both males and females
were depressed, liver and/or kidney weights were increased, and
histologic changes were noted in the liver (males) and kidneys
(females). At 100 mg/kg/day, increased liver weights were recorded in
males, with no histologic correlate, and histologic changes noted in the
kidneys of females. Transient decreases in pup body weights were seen at
the highest dosage tested, but dietary concentrations were targeted for
adults and consumption of treated diets by the pups resulted in dose
levels to the pups approximately 3-fold higher than in adults. A
teratogenic potential was not demonstrated for penoxsulam in either rats
or rabbits**.\]**

**4. *Subchronic toxicity.* \[**Dietary exposure to penoxsulam
identified the liver and/or urinary tract (kidneys and bladder) as
target organs in rats, mice and dogs following 4-week and 13-week
administration. Effects on the liver were reflected in increased liver
weights and hepatocellular hypertrophy, but these effects were not
associated with increases in mixed function oxidase (MFO) enzyme
activity. Effects noted in the kidneys included crystal deposition, most
likely from precipitation of penoxsulam from the urine, with resultant
irritation, inflammation and hyperplasia of renal pelvic transitional
epithelium. Other than the crystal deposition in the kidneys, all
effects following subchronic exposure to rats appeared to be reversible.
Very high doses were associated with significant decreases in body
weight and weight gain, and feed consumption**.\]**

**5. *Chronic toxicity.* \[**Chronic exposure in the dog indicated that
the renal effects were not exacerbated with long-term exposure.
Following long-term exposure in rats, the kidneys and urinary bladder
were the primary target organs. Histologic changes seen at the end of
2-years of exposure consisted of inflammation and hyperplasia of the
renal pelvic transitional epithelium, crystal deposition in the kidneys
and urinary bladder, and hyperplasia of the mucosa of the urinary
bladder. In the mouse, the liver was the primary target organ, and
histologic changes consisted of hepatocellular hypertrophy. There were
no treatment-related increases in tumors in either rats or mice. The
incidence of mononuclear cell leukemia (Fischer rat leukemia) was
increased in all groups of treated male rats compared to the concurrent
controls. However, the incidences in the treated groups were identical
across a 50-fold increase in dosage, and well within the range of
control values reported in the literature.

Using the Guidelines for Carcinogen Risk Assessment published September
24, 1986 (51 FR 33992), it is proposed that penoxsulam be classified as
Group E for carcinogenicity (no evidence of carcinogenicity) based on
the results of carcinogenicity studies in two species. Dow AgroSciences
believes there was no evidence of carcinogenicity in an 18-month mouse
feeding study and a 24-month rat feeding study at all dosages
tested**.\]**

**6. *Animal metabolism.* \[**Orally administered penoxsulam is rapidly
absorbed, excreted and extensively metabolized in both male and female
rats, thus, indicating that penoxsulam is not expected to accumulate in
biological systems. The majority of the residue was associated with the
parent, penoxsulam. Several metabolites were also observed but the vast
majority were \<1% of the administered dose. The major route of
metabolism involves O-demethylation, producing the OH- Penoxsulam
metabolite followed by conjugation**.\]**

**7. *Metabolite toxicology*. \[**A metabolism study with penoxsulam in
rice revealed the presence of the parent, a desmethylation metabolite
(5-OH- Penoxsulam), and two other polar metabolites, which may represent
conjugates of the desmethylated metabolite. The 5-OH-Penoxsulam
metabolite and its glucuronide and glutathione conjugates have also been
identified in the plasma and liver of rats, therefore, plant metabolites
are considered of little toxicological concern**.\]**

**8. *Endocrine disruption*. \[**Penoxsulam did not have any effects on
endocrine organs or tissues in mice, rats or dogs in any of the studies
conducted. There were no indications of effects on fetal development in
either rats or rabbits, or on reproductive performance in rats. Based on
the lack of any effects on the endocrine system, penoxsulam is not
considered an endocrine disrupter**.\]**

***C. Aggregate Exposure***

**1. *Dietary exposure.* \[**Tier 1 dietary risk assessments were
performed using DEEM-FCID™ software (version 2.14) to determine
consumption of tree nuts and grapes containing penoxsulam residues and
to determine dietary exposure resulting from consumption of tree nuts
and grapes treated with penoxsulam**.\]**

**i. *Food.* \[**Penoxsulam is registered for use as an herbicide on
rice. Therefore, consumption of rice that has been treated with
penoxsulam could result in dietary exposures. On September 24, 2004, EPA
finalized tolerances for penoxsulam in rice, grain (0.02 ppm) and rice,
straw (0.5 ppm) (69 FR 57188-57197). In establishing the tolerances for
rice, grain and rice, straw, EPA concluded that chronic dietary
exposures were \<1% of the cPAD, but exposure estimates were not
provided. On July 25, 2007, EPA finalized tolerances for penoxsulam in
fish, and shellfish. For the purposes of this aggregate assessment, it
is necessary to estimate dietary exposures of penoxsulam resulting from
tolerance level residues on rice, fish and shellfish in addition to the
proposed new uses. Secondary residues in meat, milk and poultry were not
included because the transferability of penoxsulam to edible tissues is
quite low and tolerances are not required. A chronic dietary exposure
and risk assessment for tolerance-level residues in existing and
proposed uses was performed using the DEEM-FCID™ software (version
2.14). An acute dietary assessment was not performed because no toxicity
endpoint has been identified to evaluate acute dietary exposures to
penoxsulam (EPA, 2004). To produce a conservative Tier 1 dietary risk
assessment, tolerance-level residues were assumed for all commodities,
and 100 percent crop treated was assumed for all commodities.

[]{.mark}

Dietary penoxsulam exposures range from 0.000009 mg/kg/d for Females
13-19 (not pregnant or nursing) to 0.000052 mg/kg/d for children 1-2
years. These estimated penoxsulam exposures are very low, accounting for
less than 0.1% of the cRfD (0.147 mg/kg/d) for all subpopulations**.\]**

**ii. *Drinking water.* \[**Calculation of potential acute aggregate
dietary exposure from food and drinking water was not necessary. Risk
assessment for short-term and chronic exposure to penoxsulam indicates
that drinking water is not a significant exposure pathway.

Based on the FIRST, SCI-GROW, and GENEEC2 models, the most conservative
environmental concentrations (EECs) of penoxsulam for chronic exposures
are estimated to be 0.4 ppb for surface water and 0.046 ppb for ground
water. For the purpose of these assessments, 0.4 ppb was used for the
chronic exposure estimate for water, and this value was incorporated as
a single point estimate for both "water, direct, all sources" and
"water, indirect, all sources" within DEEM-FCID food categories
exposure modeling. Based on the conservative assumptions used and using
a cPAD of 0.147 mg/kg/day, the chronic dietary exposure to penoxsulam
from all registered and proposed uses and drinking water, to all
population subgroups is approximately \<0.1% of the cPAD. Children 1-2
years old have been identified as the most highly exposed population
subgroup yet utilizing only \<0.1% of the cPAD.

It may be reasonably concluded that overall aggregate penoxsulam
exposures from the diet and drinking water uses will be associated with
a reasonable certainty of no harm**.\]**

**2. *Non-dietary exposure*. \[**Short-term exposures and MOEs for
handlers making applications of penoxsulam for tree nut and grape
vegetation control are estimated to range from 340,000 to \>2,000,000 ,
depending on the work function performed (M/L open/closed system; or
applying liquids open/closed cab). These MOEs, which are considerably in
excess of the target of 100, indicate that penoxsulam may be applied
according to label instructions with a reasonable certainty of no harm
for mixer/loader/applicators.

[]{.mark}

Adult residential exposure MOEs during and post application were
\>1,000,000 and \>60,000 respectively. Residential exposure MOE for
children (dermal, soil ingestion, OtM, HtM) was calculated to be 13,000.
An aggregate risk assessment was conducted for chronic exposure from
drinking water and dietary intakes and the short-term exposure during
residential application for penoxsulam, as pertains to uses on turf
according to the EPA SOP for aggregate assessment guidance document
(EPA, 1999). The short-term aggregate total MOEs range from 12,000 for
toddlers to 370,000 for adults. The long-term aggregate total MOEs range
from 12,000 for toddlers to 56,000 for adults. As these values
illustrate, conservatively estimated total aggregate MOEs for all
dietary, oral (incidental non-dietary), drinking water and dermal
exposures are greater than 100. Thus, anticipated aggregate exposures
estimated with conservative assumptions regarding use patterns of the
full range of registered and proposed penoxsulam products are not of
concern**.\]**

***D. Cumulative Effects***

**\[**Currently, no methodologies are available to resolve the complex
scientific issues concerning common mechanism of toxicity and cumulative
exposure and risk. The U.S. EPA has begun a pilot process to study this
issue further through the examination of particular classes of
pesticides. Thus, Dow AgroSciences believes it is appropriate to
consider only the potential risks of penoxsulam in its exposure
assessment**.\]**

***E. Safety Determination***

**1. *U.S. population.* \[**Using the conservative exposure assumptions
described above, and based on the completeness and reliability of the
toxicity data, the aggregate exposure to penoxsulam, as determined under
the guidance of the FQPA, will utilize less than 0.1% of the RfD from
the dietary exposure for all subgroups of the U.S. population. Generally
and under the FQPA, the U.S. EPA has no concern for exposures below 100%
of the RfD because the RfD represents the level at or below which daily
dietary exposure over a lifetime will not pose appreciable risks to
human health. Additionally, the chronic dietary exposure to penoxsulam
from all registered and proposed uses and drinking water, to all
population subgroups is approximately \<0.1% of the cPAD. Therefore,
there is a reasonable certainty that no harm will result to the general
U.S. population from aggregate exposure to penoxsulam residues from the
proposed use**.\]**

**2. *Infants and children*. \[**In assessing the potential for
additional sensitivity of infants and children to residues of
penoxsulam, data from developmental toxicity studies in rats and rabbits
and a multi-generation reproduction study in the rat are considered. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from pesticide exposure during
prenatal development. Reproduction studies provide information relating
to effects from exposure of both parents to the pesticide on the
reproductive capability and potential systemic toxicity of mating
animals and on various parameters associated with the well being of
offspring.

FFDCA section 408 provides that the U.S. EPA may apply an additional
safety factor for infants and children in the case of threshold effects
to account for pre- and post-natal toxicity and the completeness of the
database. Based on the current toxicological data requirements, the
database for penoxsulam relative to pre- and post-natal effects for
children is complete. Overall, penoxsulam had no effect on reproduction
or embryo-fetal development at any dosage tested. No quantitative or
qualitative susceptibility was seen following pre- and post-natal
exposures. In a rabbit developmental toxicity study, effects on in-utero
survival were observed only at a dose level where clear maternal
toxicity was seen. In a 2-generation reproductive toxicity study in
rats, no effects on reproductive performance were observed and effects
on neonatal growth were seen only at a dose level where parental
toxicity was seen. In addition, the NOAEL in the chronic dog study (14.7
mg/kg/day), used to calculate the chronic RfD (0.147 mg/kg/day), is
already lower than the NOAEL from the rabbit developmental study (25
mg/kg/day). Therefore, an additional FQPA uncertainty factor is not
needed and the RfD at 0.147 mg/kg/day is appropriate for assessing risk
to infants and children. Using the conservative exposure assumptions
previously described, the percent RfD utilized by the potential exposure
to residues of penoxsulam is less than 0.1% for children 1-2 years, the
population subgroup predicted to be potentially the most highly exposed.
Based on the aggregate exposure to penoxsulam, Dow AgroSciences
concludes with reasonable certainty that no harm will result to infants
and children, females 13+ years old and the prenatal development of
infants**.\]**

***F. International Tolerances***

**\[**A review of Maximum Residue Limits (MRLs) established globally
indicates that no corresponding MRLs have been established for
penoxsulam in or on grapes, pistachios or tree nuts. However,
registration has been requested on grapes in France where the proposed
MRL is 0.01 mg/kg. Residues in the grapes in the trials in France were
not detected and the proposed MRL is based on the LOQ of the analytical
method**.\]**