Document ID: EPA-HQ-OPP-2008-0526-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-28T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  29 January 2009

SUBJECT:	Penoxsulam. Section 3 Registration Application For Use of
GF-443 T&V on Grape and Tree Nuts Including Pistachio.  Summary of
Analytical Chemistry and Residue Data.

PC Code:  119031	DP Barcode:  D355914

Decision No.:  394768	Registration No.:  62719-ANG

Petition No.:  8F7369	Regulatory Action:  Section 3

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  219714-96-2

MRID No.:  See MRID Summary Table	40 CFR:  180.605

FROM:	Michael A. Doherty, Ph.D., Chemist

Risk Assessment Branch II

Health Effects Division (7509P)

THROUGH:	Dennis McNeilly, Chemist

		Christina Swartz, Branch Chief

Risk Assessment Branch II

Health Effects Division (7509P)

TO:		Philip Errico/Joanne Miller (Team 23)

		Herbicide Branch

		Registration Division (7505P)  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r
1 

		

MRID Summary Table

MRID No.	Study Type	Comments

46389701	860.1340 Crop commodities	DER; 46389701.der.doc

47444401	860.1300 Grape	DER; 47444401.der.doc

47444402	860.1380 Grape	DER; 47444402.der.doc

47444403	860.1500 Grape	DER; 47444403.de1.doc

	860.1520 Grape	DER; 47444403.de2.doc

47444404	860.1500 Almond	DER; 47444404.der.doc

47444405	860.1500 Pecan

	

  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (2275 Research Boulevard, Suite 300;
Rockville, MD 20850).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.  

Executive Summary

Penoxsulam is a sulfonamide herbicide currently registered for the
selective control of grass, broadleaf, and sedge weeds.  In the U.S., it
was first registered for use on rice and subsequently has been
registered for use on turf and for use in aquatic weed control.  The
herbicide’s mode of action at the cellular level involves the
inhibition of acetolactate synthase (ALS).  

Dow AgroSciences LLC has submitted a Section 3 registration application
for the end-use product GF-443 T&V (EPA File Symbol No. 62719-ANG), a 2
lb/gal suspension concentrate (equivalent to a flowable concentrate,
FlC) formulation, for use on grapes and tree nuts.  The proposed use
allows broadcast or banded soil application to the orchard/vineyard
floor as a winter dormant application followed by an application in the
spring, for a maximum seasonal rate of 0.047 lb ai/A, with a minimum
retreatment interval (RTI) of 30 days and a preharvest interval (PHI) of
60 days for grapes and tree nuts.  In conjunction with the requested
uses, Dow AgroSciences has submitted a petition (PP#8F7369) for the
establishment of permanent tolerances for residues of penoxsulam
[2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-
2-yl)-6-(trifluoromethyl)benzenesulfonamide] in or on the following raw
agricultural commodities:

Almond, hulls 	0.01 ppm

Grape 	0.01 ppm

Nuts, tree, group 14 	0.01 ppm

Pistachio 	0.01 ppm

Permanent tolerances are established under §180.605(a) for residues of
penoxsulam per se in/on rice grain and straw (0.02 and 0.50 ppm), and
fish, crustacean shellfish, and mollusc shellfish at 0.01-0.02 ppm.

Data requirements for the proposed uses of penoxsulam on grapes and tree
nuts were previously evaluated by ChemSAC (minutes of the 1/24/07
meeting), and recommendations were made concerning the plant metabolism,
crop field trial, and processing studies submitted under PP#8F7369.

The nature of the residue in plants is understood for purposes of this
petition.  The residue of concern for tolerance expression and risk
assessment is penoxsulam per se.  An acceptable rice metabolism study
reflecting foliar application was previously submitted.  Under the
current petition, an acceptable grape metabolism study reflecting soil
application has been submitted.  ChemSAC previously concluded that the
subject grape metabolism study would be adequate to determine the nature
of the residue for the proposed uses on grapes and tree nuts in
consideration of the proposed use patterns.  Both the rice and grape
metabolism studies demonstrate that penoxsulam primarily degrades to its
5-OH metabolite (5-OH XDE-638); little translocation of penoxsulam or
its metabolites into rice grain or grape vines was observed.  HED notes
that, should the use pattern for grapes or tree nuts change (i.e., from
soil to foliar applications), additional nature of the residue data will
be needed.

The nature of the residue in livestock is understood based on adequate
goat and poultry metabolism studies.  The studies indicated that
penoxsulam is primarily excreted and not significantly metabolized in
either goats or poultry.  The sulfonanilide bridge in penoxsulam does
not appear to be cleaved.  The residue of concern for penoxsulam in
livestock is parent only.

An acceptable data collection method, LC/MS/MS Method GRM 04.09, was
used for the determination of residues of penoxsulam in the grape
storage stability study, grape and tree nut field trials, and grape
processing study.  The validated limit of quantitation (LOQ) is 0.01 ppm
in grape and tree nut matrices.  HED concludes that Method GRM 04.09 is
also suitable for the enforcement of tolerances in grape and tree nut
commodities.  Because the method monitors two ion transitions, no
confirmatory method is required, and because the method is similar to
the tolerance enforcement methods for rice (Method GRM 01.25) and fish
and shellfish (Method GRM 05.08), no independent laboratory validation
(ILV), radiovalidation, or petition method validation (PMV) is required.
 

The FDA multiresidue protocol data show that penoxsulam is not
adequately recovered using any of the protocol methods.  

The only livestock feedstuff associated with the proposed uses is almond
hulls which may be fed to dairy cattle; almond hulls are not considered
a significant feedstuff of beef cattle, poultry, or swine.  A dietary
burden for cattle, poultry and swine was previously calculated based on
the contribution of penoxsulam resulting from rice and aquatic uses,
with the greatest contribution to the dietary burden (0.150 ppm) from
treated water.  At that time, HED concluded that if no inadvertent
residues occurred in crops irrigated with penoxsulam-treated water, the
aquatic uses of penoxsulam could result in a 40 CFR §180.6(a)(3)
situation for ruminant and poultry commodities; i.e., there would be no
reasonable expectation of finite residues in ruminant and poultry
commodities and no ruminant or poultry feeding study would need to be
submitted.  Based on the available tree nut field trial results, the
dietary contribution of almond hulls to the dairy cattle dietary burden
would be minimal (0.001 ppm), and would not affect HED’s previous
conclusions concerning livestock tolerances.

The storage conditions and durations of samples from the grape and tree
nut field trials and grape processing study are supported by adequate
storage stability data.  

Adequate crop field trial data have been submitted in support of the
proposed uses on grapes and tree nuts.  Residues of penoxsulam were
nonquantifiable (<0.01 ppm) in/on all samples of grape, almond and pecan
nutmeats, and almond hulls harvested following soil treatment.  The
submitted field trial data will support the proposed tolerances at the
LOQ of 0.01 ppm for residues of penoxsulam in/on grape, the tree nut
crop group, almond hulls, and, by translation of the almond data,
pistachio.

An adequate grape processing study was submitted.  Residues of
penoxsulam were nonquantifiable (<0.01 ppm) in grape harvested following
soil treatment at 5.8x the maximum proposed seasonal application rate or
in the processed commodities of juice and raisin; therefore, no
tolerances are needed for grape processed commodities.  

Because grapes and tree nuts are not rotated, no data pertaining to
rotational crops are required to support the proposed uses.  

There are no Codex, Canadian or Mexican MRLs established for residues of
penoxsulam in crops associated with this review.  However, the
petitioner noted that registration has been requested on grapes in
France with a proposed MRL of 0.01 ppm (based on the analytical method
LOQ).

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

There are no residue chemistry issues that would preclude granting
registration for the requested uses of penoxsulam on grape and tree nuts
or establishment of permanent tolerances for penoxsulam residues as
follows:  SEQ CHAPTER \h \r 1 

Almond, hulls 	0.01 ppm

Grape 	0.01 ppm

Nut, tree, group 14 	0.01 ppm

Pistachio 	0.01 ppm

Prior to registration, the petitioner should submit a revised Section F
to reflect the correct commodity definition for the tree nut crop group:
 “Nut, tree, Group 14.”  A human-health risk assessment is
forthcoming in a separate document. (D355595).

Note to RD:  As a result of the revisions to Table 1 of OPPTS Test
Guideline 860.1000 (Memorandum dated 6/30/08, Chemistry Science Advisory
Council), rice straw has been removed as a significant livestock feed
item and therefore, the established tolerance for residues of penoxsulam
in/on rice straw could be removed.

Background

The nomenclature of penoxsulam is summarized in Table 1, and the
physicochemical properties are summarized in Table 2.  The chemical
names and structures of penoxsulam and all metabolites identified in the
plant commodities are presented in Appendix I.

Table 1.	Penoxsulam Nomenclature.

Compound	

Common name	Penoxsulam

Company experimental name	XDE-638

IUPAC name	  SEQ CHAPTER \h \r 1
6-(2,2-difluoroethoxy)-N-(5,8-dimethoxy-s-triazolo[1,5-c]pyrimidin-2-yl)
-α,α,α-trifluoro-o-toluenesulfonamide

CAS name	  SEQ CHAPTER \h \r 1
2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]
pyrimidin-2-yl)-6-(trifluoromethyl) benzenesulfonamide

CAS registry number	  SEQ CHAPTER \h \r 1 219714-96-2

End-use product (EP)	GF-443 T&V Herbicide (EPA Reg. No. 62719-ANG) 

Table 2.	Physicochemical Properties of Penoxsulam. 

Parameter	Value	Reference 1

Melting point/range	Not available

	pH	5.2	MRID 45830707

Density	1.61 g/mL at 20 °C 	MRID 45830707

Water solubility at 19 °C	Unbuffered	4.91 mg/L

pH 5	5.66 mg/L

pH 7	408 mg/L

pH 9	1460 mg/L	MRID 45830720

Solvent solubility at 19 °C	Xylene	0.017 g/L

1-Octanol	0.035 g/L

Methanol	1.48 g/L

Ethyl acetate	3.23 g/L

Acetonitrile	15.3 g/L

Acetone	20.3 g/L 

Dimethylsulfoxide	78.4 g/L	MRID 45830720

Vapor pressure	  SEQ CHAPTER \h \r 1 7.16 x 10-16 mm Hg at 25 °C	MRID
45830720

Dissociation constant, pKa	5.1 (ambient)	MRID 45830720

Octanol/water partition coefficient, Log(KOW)	Unbuffered	  SEQ CHAPTER
\h \r 1 -0.354

pH 5	  SEQ CHAPTER \h \r 1 1.137

pH 7	  SEQ CHAPTER \h \r 1 -0.602

pH 9	  SEQ CHAPTER \h \r 1 -1.418	MRID 45830720

UV/visible absorption spectrum	Not available

	1 As referenced in DP# 326985, 1/30/07, D. Soderberg.

860.1200  Directions for Use

™ SC; EPA Reg. No. 62719-500) which is registered for use on rice in
the U.S.  The proposed uses on grapes and tree nuts are summarized in
Table 3.

Table 3.	Summary of Directions for Use of Penoxsulam.

Applic. Timing, Type, and Equip.	Formulation

[EPA File Symbol No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Grape

Winter dormant + spring;

Soil; broadcast to crop floor or banded at base of trunk;

Ground; use of a hooded/shielded sprayer is required for application
after petal fall.	2 lb/gal FlC

[62719-ANG]	0.0312 (dormant)

0.0156 (spring)	2	0.0469	60	Winter dormant application followed by an
application in the spring with an appropriate postemergence tank mix
partner in spray volumes ≥20 gal/A.  A minimum RTI of 30 days is
specified. Application to vines that are not staked or trellised unless
they are free standing, or to vines established <1 year, or to vines
established <3 years unless they are on a trellis wire 3’ above the
soil surface is prohibited.   

Tree Nuts

Winter dormant + spring;

Soil; broadcast to crop floor or banded at base of trunk;

Ground; use of a hooded/shielded sprayer is required for application
after flowering.	2 lb/gal FlC

[62719-ANG]	0.0312 (dormant)

 in spray volumes ≥20 gal/A.  A minimum RTI of 30 days is specified.
Application to tree nut crops established <9 months is prohibited.   

Note to RD:  The proposed use pattern on the draft label differed from
the use pattern described under Section G of the petition, where the
petitioner stated that the maximum application rates for winter dormant
applications were 0.0357 lb ai/A for grape and 0.0446 lb ai/A for tree
nut, and that the maximum application rate for the second application
was 0.0179 lb ai/A for both crops for maximum seasonal rates of 0.0535
lb ai/A for grape and 0.0624 lb ai/A for tree nuts.  The rates specified
under Section G correspond more closely with the use patterns reflected
in the crop field trials.  Given that the residues in the field trials
are all < LOQ, HED has no concerns if the rates specified in Section G
are the truly intended rates and become listed on the final label.

The following restrictions are specified for both grape and tree nut
uses:  (1) do not apply as an over-the-top application; (2) do not apply
to any soil that is classified as a sandy soil or to soils with <1%
organic matter; (3) do not apply until soil has been settled by packing
and irrigation or rainfall and no cracks are present; (4) do not apply
through any type of irrigation system; and (5) do not use treated plants
for feed or forage, and do not feed or allow animals to graze treated
areas.

The following general instructions are specified for both grape and tree
nut uses:  (1) for best weed control, apply as a single winter dormant
application following final harvest up to February 15th; a sequential
application may be applied up to 60 days prior to harvest; (2) direct
spray toward the base of trees or vines, avoid direct or indirect
application to green foliage or green bark; (3) a single rainfall or
sprinkler irrigation of ≥0.5”, or flood irrigation after application
is necessary to activate the product; and (4) for all applications where
postemergence weed control is desired and to improve foliar spray
coverage, the addition of a crop oil concentrate or methylated seed oil
is required.

Several tank mix partners are identified for both grape and tree nut
uses.  The tank mixing instructions state that in interpreting the
labels of tank-mixed products, the most restrictive label limitations
apply; a jar test for compatibility is recommended.  The following tank
mix partners are identified for postemergence (residual) control of
grass and broadleaf weeds:  glyphosate, glufosinate or paraquat.  The
following tank mix partners are identified for preemergence control of
grass and broadleaf weeds:  oxyfluorfen (GoalTender, Goal 2XL), isoxaben
(Gallery), diuron (Karmex), pronamide (Kerb herbicide), simazine,
norflurazon (Solicam), flumioxazin (Chateau), oryzalin (Surflan), or
pendimethalin (Prowl).  

Conclusions.  The submitted use pattern information is adequate to allow
evaluation of the residue data relative to the proposed use.  

The crop field trial data submitted to support use of the 2 lb/gal FlC
formulation of penoxsulam were generated using a 25 g/L oil dispersion
(OD) formulation of penoxsulam.  Because the OD and FlC formulations are
prepared similarly (i.e., both are diluted with water for application
and require constant agitation during application), and applications are
made to the soil, the field trial data generated using the 25 g/L OD
formulation may be translated to support the proposed use of the 2
lb/gal FlC formulation on grapes and tree nuts.

860.1300 Nature of the Residue - Plants

DER Reference:	47444401.der.doc

PP#3F6542; DP# 288152, 8/11/04, W. Cutchin

An acceptable rice metabolism study was previously reviewed in
conjunction with the rice petition (PP#3F6542).  Based on the submitted
rice metabolism study, following foliar application, penoxsulam
primarily degrades to its 5-OH metabolite (5-OH XDE-638) and at least
two minor unknown metabolites in rice matrices; little translocation of
penoxsulam residues or its metabolites into rice grain was observed.

Based on this study HED determined that the residue of concern for
tolerance expression and risk assessment for penoxsulam in/on rice is
parent only.  HED further noted that for any future uses on other crops,
additional nature of the residue data would be needed.  Alternatively,
the petitioner might submit crop field trial data that include residue
data for the metabolite 5-OH XDE-638 as well as parent.

Grape

Dow AgroSciences has submitted a study investigating the metabolism of
[phenyl-U-14C]penoxsulam (PH label; specific activity 25.7 mCi/mmol) and
[triazolopyrimidine-14C]penoxsulam (TP label; specific activity 28.2
mCi/mmol) in grape grown outdoors in treated sandy clay loam soil.  The
test substances, diluted with water, were applied as a single spray
application to the soil around grape vines at a target rate of 0.018 lb
ai/A.  The application rate corresponds to ~1.2x the maximum proposed
application rate for application during the spring (growing stage) to
grapes and tree nuts.  The application was made when grapes were at the
BBCH 55 growth stage (first flower buds enlarged), and mature grapes and
leaves were harvested 118 days following treatment.  The in-life phase
of the study was conducted by Research For Hire (Porterville, CA), and
the analytical phase of the study was conducted by Dow AgroSciences LLC,
Regulatory Laboratories (Indianapolis, IN).

Total radioactive residues (TRR), determined by combustion/LSC, were
below the LOQ (<0.0008 ppm) in grapes (both labels), and 0.016 and 0.013
ppm, respectively, in PH- and TP-label grape leaves following soil
treatment at 0.017-0.018 lb ai/A.   

Grape samples were not extracted due to very low radioactivity (<0.001
ppm).  The majority of the radioactivity for both labels (~63-69% TRR)
was released from grape leaves with acetonitrile (ACN) and water solvent
extraction.  The extracted residues were almost equally partitioned into
organic (33-40% TRR) and aqueous (30% TRR) fractions.  Nonextractable
residues were <0.01 ppm in grape leaves.  These procedures adequately
extracted the majority of residues from grape leaves.  Extraction and
partitioning results were normalized by the petitioner, resulting in
accountabilities of 100%; actual recoveries following extraction
(extract + pellet) were 94.4% and 117.5%, and following partitioning
were 113% and 119% for the PH- and TP-label leaves, respectively.

Residues were only tentatively identified in grape leaves by HPLC
comparison with reference standards, due to low levels of individual
components (each <0.01 ppm).  No storage stability data are required to
support the study because all samples were stored frozen and were
analyzed within 3 months of collection.

 for 6.3-10% TRR and 3.9-9.0% TRR (each ≤0.001 ppm), respectively. 
The majority of the aqueous-soluble residues (19.1-21.3% TRR,
0.002-0.003 ppm) were polar, eluting in the solvent front.  Multiple low
level components, present individually at ≤5.4% TRR, were
characterized as organo- or aqueous-soluble and accounted for 24.5-29.2%
TRR (≤0.004 ppm) in leaves.   

Very low levels of soil-applied penoxsulam and its degradates were
translocated into the grape vines.  Based on the submitted study, the
metabolism of penoxsulam proceeds via O-demethylation at both the
5-methoxy and 8-methoxy positions, as well as through undetermined
alterations to form multiple, low-level unknowns.

Conclusions.  ChemSAC previously concluded (minutes of 1/24/2007
meeting) that, provided the subject grape metabolism study had been
accurately described by Dow, the study would be adequate to determine
the nature of the residue for uses on grapes, tree nuts, and citrus in
consideration of the proposed use patterns:  soil application with the
second application made at a lower rate and at an earlier growth stage
than reflected in the grape metabolism study.

The submitted grape metabolism study is acceptable.  Very low levels
(<0.001 ppm) of soil-applied penoxsulam and its degradates were
translocated into grape.  The application rate used in the study is
slightly higher than the maximum application rate proposed for the
second application to grapes and tree nuts, and, although the PHI
reflected in the study is longer than the proposed PHI (118 days vs. 60
days), it is not anticipated that soil application at a higher rate or
at a shorter PHI would result in significantly higher residues in
grapes. 

HED concludes that for purposes of this petition only, the nature of the
residue in grapes and tree nuts is understood.  The residue of concern
for tolerance expression and risk assessment is penoxsulam per se.  

HED notes that, should the use pattern for grapes or tree nuts change
(i.e., from soil to foliar applications), additional nature of the
residue data would be needed.

860.1300 Nature of the Residue - Livestock

PP#3F6542; DP# 288152, 8/11/04, W. Cutchin 

Acceptable animal metabolism studies were reviewed in conjunction with
the rice petition (PP#3F6542).  The available goat and poultry
metabolism data indicate that penoxsulam is primarily excreted and not
significantly metabolized in either goats or poultry.  Because no
significant differences were observed in metabolism of phenyl and
triazolopyrimidine ring-labeled penoxsulam in the goat metabolism study,
the sulfonanilide-bridge in penoxsulam does not appear to be cleaved.

HED determined that for tolerance expression and risk assessment, the
residues of concern for penoxsulam in livestock (including poultry) is
parent only.  

860.1340 Residue Analytical Methods

DER Reference:	46789701.der.doc

PP#5F7012; DP# 326985, 1/30/07, D. Soderberg

PP#3F6542; DP# 288152, 8/11/04, W. Cutchin

PP#3F6542; DP# 303172, 7/19/04, W. Cutchin

Enforcement methods:   Dow AgroSciences LLC previously proposed LC/MS/MS
method GRM 01.25 for the enforcement of tolerances for residues of
penoxsulam in/on rice commodities (PP#3F6542).  Using this method,
samples of rice matrices are extracted with ACN/water.  An aliquot of
the supernatant is diluted with water and cleaned up on a mixed-mode
polymeric-anion exchange solid phase extraction (SPE) plate.  Residues
are eluted with ACN:formic acid (99.9:0.1, v:v), evaporated to dryness,
and redissolved in mobile phase.  Residues are quantitated by LC/MS/MS
using a C8 column, a gradient mobile phase of ACN/methanol and water,
each containing 0.1% acetic acid, and electrospray ionization in the
positive ion mode.  Residues are quantified using external standards. 
The validated LOQ was 0.01 ppm in/on rice forage, straw, grain, hulls,
bran, and polished rice.

Method GRM 01.25 underwent a successful ILV; neither radiovalidation nor
a confirmatory method was required.  Based on the available information,
HED has already concluded that the method is acceptable for tolerance
enforcement and an Agency method validation was requested.  At this
time, the Agency method validation does not appear to have been
completed.  Current policy now places the determination of the need for
Agency method validation within the purview of HED.  HED believes that
the available data show the method to be valid for enforcement purposes
without further Agency review.

A second LC/MS/MS method, Method GRM 05.08, was submitted in conjunction
with proposed use of penoxsulam in aquatic sites (PP#5F7012) for the
determination of residues in meat, milk and fish.  Using this method,
residues are extracted with ACN/water, and the extract is diluted with
0.1 N HCl for cleanup on a 96-well polymeric SPE plate.  A stable
isotope penoxsulam internal standard is added to the extract prior to
LC/MS/MS analysis, and two ion transitions are monitored.

Method GRM 05.08 also underwent a successful ILV; no radiovalidation
data were required.  Because the method monitors two ion transitions, no
confirmatory method is needed.  HED concluded that because Method 05.08
was similar to Method 01.25, using reasonable similar extraction
procedures, the method would be suitable for enforcement purposes for
fish and shellfish tissues, provided the petitioner supplied the stable
isotope internal standard to the EPA National Pesticide Standards
Repository.

Data-collection method:    SEQ CHAPTER \h \r 1 Dow AgroSciences has
submitted an LC/MS/MS method, Method GRM 04.09, for the determination of
residues of penoxsulam in/on acidic, dry, oily, and wet crops.  This
method was used for data collection in the grape storage stability
study, grape and tree nut crop field trial studies, and grape processing
study submitted under DP# 355914.  Method GRM 04.09 is the same as the
enforcement method for fish and shellfish, Method GRM 05.08.  

Briefly, samples are extracted with ACN:water (80:20, v:v).  The extract
is diluted with 0.1 N HCl and purified through a 96-well polymeric
reverse phase SPE plate.  Residues are eluted with ACN into another
96-well SPE plate containing ACN:methanol:water (15:15:70, v:v:v,
containing 0.1% acetic acid) mobile phase and a stable isotope internal
standard.  The final solution is analyzed by LC/MS/MS for residues of
penoxsulam.  The calculated method LOQs are 0.0044 ppm for acidic crops,
0.0052 ppm for dry crops, 0.0054 ppm for oily crops, and 0.0081 ppm for
wet crops.

Acceptable method validation recoveries were obtained for penoxsulam
from samples of acidic, dry, oily, and wet crop matrices fortified at
0.01 and 1.0 ppm.  Acidic crop matrices included orange whole fruit,
pulp, and peel; lemon whole fruit; and apple.  Dry crop matrices
included wheat, rice, and barley grain, forage, and straw; field corn
grain, forage, and stover, and sunflower seed.  Oily matrices included
canola and soybean seed, olive oil, and olive fruit without seed; and
wet matrices included grape, potato tuber, sugar beet root, and
broccoli.  Recoveries were within the acceptable range of 70-120% for
all samples at all fortification levels.  

No confirmatory analysis procedures were included for the proposed
enforcement method; however, because the LC/MS/MS method monitors two
ion transitions for penoxsulam, a confirmatory method is not needed.

No radiovalidation data were submitted for Method GRM 04.09.  HED has
concluded that radiovalidation of the method is not required because the
extraction solvent used for the method is the same as that used in the
rice and grape metabolism studies.

Conclusions.  The submitted data are adequate to satisfy data
requirements.  Method GRM 04.09 is acceptable for data collection for
grape and tree nut commodities based on acceptable concurrent method
recoveries.  No enforcement method was proposed in the subject petition;
however, HED concludes that Method GRM 04.09 is suitable for the
enforcement of tolerances in grape and tree nut commodities.  ILV of
Method GRM 04.09 is not required because the method is the same as
Method GRM 05.08 for which a successful ILV was conducted.  Based on the
available information regarding method performance and the successful
ILV of Method GRM 0508, an Agency Petition Method Validation (PMV) is
not required.  

860.1360 Multiresidue Methods

PP#3F6542; DP# 288152, 8/11/04, W. Cutchin 

Testing results of penoxsulam analyzed according to the FDA
Multi-Residue Method Test guidelines in PAM Vol. I, Appendix II (1/94)
were previously submitted in conjunction with the rice petition (PP#
3F6542).  The multiresidue method data indicate that penoxsulam is not
adequately recovered using any of the multiresidue methods.  These data
have been forwarded to FDA for further evaluation.

860.1380 Storage Stability

DER Reference:	47444402.der.doc

DP# 328689, 12/18/06, D. Soderberg

PP#3F6542; DP# 288152, 8/11/04, W. Cutchin

Storage stability data were previously submitted (PP#3F6542) and
indicate that residues of penoxsulam are stable under frozen storage
conditions in rice grain, straw, and immature forage for up to 732 days
(24 months), and in processed rice bran, hulls, and polished rice for up
to 390 days (12.8 months).  

In conjunction with the subject petition, Dow AgroSciences has submitted
the results of a storage stability study with penoxsulam in grape. 
Homogenized samples of untreated grapes were fortified with penoxsulam
at 0.10 ppm, stored frozen (~-20 °C), and analyzed at storage intervals
of 0, 28, 90, 176, and 359 days.  Grape samples were analyzed for
residues of penoxsulam using LC/MS/MS Method GRM 04.09.  The method is
adequate for data collection based on acceptable concurrent method
recoveries.  The reported method LOQ is 0.01 ppm for penoxsulam in/on
grape.  The data indicate that residues of penoxsulam are stable in/on
grape stored frozen for up to 359 days.

The storage durations and conditions of samples from the crop field
trials and processing studies submitted to support this petition are
presented in Table 4.  

Table 4.	Summary of Storage Conditions and Durations of Samples from
Crop Field Trial and Processing Studies.  

Matrix 	Storage

Temperature

 (°C)	Actual Storage Duration	Interval of Demonstrated Storage
Stability

Grape	~-20	179-232 days (5.9-7.6 months)	Residues of penoxsulam are
stable in/on grape stored frozen for up to 11.8 months.

Grape (for processing)

195 days (6.4 months)

	Grape, juice

189 days (6.2 months)	None available.

Raisin

187 days (6.2 months)

	Almond, nutmeat and hulls

202-234 days (6.6-7.7 months)

	Pecan, nutmeat

119-151 days (3.9-5.0 months)

	

Conclusions.  The storage conditions and durations of samples from the
grape and tree nut field trials and grape processing study are supported
by adequate storage stability data.  The concurrent storage stability
data for grape are adequate to support the grape field trials. 
Supporting storage stability data will not be required for juice or
raisin samples from the grape processing study, because penoxsulam
residues were nondetectable in/on the grape RAC treated at an
exaggerated rate, thus a processing study would not have been required.

Although the stability of penoxsulam has not been demonstrated in five
diverse crops, the available storage stability data for rice raw
agricultural and processed commodities and grapes will be considered
adequate to support the storage conditions and durations of almond and
pecan nutmeat and almond hull samples from the tree nut field trials,
given that soil applications were made, nonquantifiable residues were
observed, and no stability issues are likely for penoxsulam. 

860.1400 Water, Fish, and Irrigated Crops

There are no proposed uses that are relevant to this guideline topic.

860.1460 Food Handling

There are no proposed uses that are relevant to this guideline topic.

860.1480 Meat, Milk, Poultry, and Eggs

PP#5F7012; DP# 326985, 1/30/07, D. Soderberg

No animal feeding studies were submitted with this petition.  The only
livestock feedstuff associated with the proposed uses on grape and tree
nuts is almond hulls which may be fed to dairy cattle; almond hulls are
not considered a significant feedstuff of beef cattle, poultry, or
swine.  

A dietary burden for cattle, poultry, and swine was previously
calculated based on the contribution of penoxsulam resulting from rice
and aquatic uses.  Dietary burdens of 0.220 ppm for beef and dairy
cattle, 0.170 ppm for poultry, and 0.166 ppm for swine were calculated,
with the greatest contribution to each dietary burden (0.150 ppm) coming
from treated water.  HED concluded that if no inadvertant residues
occurred in crops irrigated with penoxsulam-treated water, the aquatic
uses of penoxsulam could result in a 40 CFR §180.6(a)(3) situation for
ruminant and poultry commodities; i.e., there would be no reasonable
expectation of finite residues in ruminant and poultry commodities and
no ruminant or poultry feeding study would need to be submitted.  This
conclusion was considered tentative, pending submission of a study on
the magnitude of the residue in irrigated crops to support the aquatic
uses.  If significant residues are found in crops irrigated with
penoxsulam-treated water, then livestock feeding studies may be
required.  

Conclusions.  No additional data are required to support the proposed
uses of penoxsulam on grapes and tree nuts.  Based on the available crop
field trial results, the dietary contribution of almond hulls to the
dairy cattle dietary burden would be minimal (0.001 ppm), and would not
affect HED’s previous conclusions concerning livestock tolerances. 

860.1500 Crop Field Trials

DER References:	47444403.de1.doc (grape)

		47444404.der.doc (tree nuts; includes review of MRID 47444405)

Table 5.	Summary of Residue Data from Crop Field Trials with Penoxsulam.

Crop matrix	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels (ppm)

	n	Min.	Max.	HAFT1	Median	Mean	Std.

Dev.

Grape (proposed use = 0.0312 lb ai/A during the dormant stage + 0.0156
lb ai/A during the growing stage, for a total application rate of 0.0469
lb ai/A; 60-day PHI)

Grape	0.054-0.056	59-60	8	<0.01	<0.01	<0.01	<0.01	<0.01	--

Tree Nuts (proposed use = 0.0312 lb ai/A during the dormant stage +
0.0156 lb ai/A during the growing stage, for a total application rate of
0.0469 lb ai/A; 60-day PHI)

Almond, nutmeat	0.062-0.063	59-60	6	<0.01	<0.01	<0.01	<0.01	<0.01	--

Almond, hulls	0.062-0.063	59-60	6	<0.01	<0.01	<0.01	<0.01	<0.01	--

Pecan, nutmeat	0.062-0.064	55-60	6	<0.01	<0.01	<0.01	<0.01	<0.01	--

1  HAFT = Highest average field trial result.

Grape

Dow AgroSciences has submitted crop field trial data for penoxsulam on
grape.  Four grape field trials were conducted in the United States in
Zones 1 (NY; 1 trial), 10 (CA; 2 trials), and 11 (WA; 1 trial), during
the 2007 growing season.  

At each test location, two soil applications were made with a 25 g/L OD
formulation of penoxsulam.  The first application was made near the end
of the grape vine dormant stage (bud swell; BBCH 0-5) at a target rate
of 0.0357 lb ai/A, and the second application was made 81-130 days
later, during the growing stage (BBCH 77-79), at a target rate 0.0179 lb
ai/A, for a total seasonal rate of ~0.054 lb ai/A.  The application
rates used in the study correspond to ~1.1x the maximum proposed rates
for applications at the dormant and growing stages, and to ~1.2x the
maximum proposed seasonal rate.  Broadcast applications were made to the
vineyard floor, using ground equipment, in ~20-26 gal/A spray volumes
with crop oil concentrate as an adjuvant.  Samples of untreated and
treated grapes were harvested at commercial maturity, 59-60 days after
the last application.

Grape samples were analyzed for residues of penoxsulam using LC/MS/MS
Method GRM 04.09.  The method is adequate based on acceptable concurrent
method recoveries.  The validated LOQ is 0.01 ppm for grapes.

The storage conditions and durations for grape samples are reported in
Table 4.  The storage stability data for grape submitted in conjunction
with the subject petition adequately support the storage conditions and
durations of samples from the grape field trials.

The results of the grape field trials are summarized in Table 5. 
Residues of penoxsulam were nonquantifiable (<0.01 ppm) in/on all
samples of grape harvested 59-60 days following two soil broadcast
applications of the 25 g/L OD formulation at a total rate of 0.054-0.056
lb ai/A.

Tree nut, group 14

Dow AgroSciences has submitted crop field trial data for penoxsulam on
almonds and pecans, the representative crops of the tree nut crop group
14.  Six tree nut trials were conducted in the United States during the
2007 growing season.  Three almond trials were conducted in Zone 10
(CA), and three pecan trials were conducted in Zones 2 (GA), 4 (LA), and
8 (TX).

At each test location, two soil applications were made with a 25 g/L OD
formulation of penoxsulam.  The first application was made near the end
of the dormant stage (bud swell) at a target rate of 0.0446 lb ai/A, and
the second application was made 125-196 days later, during the growing
stage, at a target rate of 0.0178 lb ai/A, for a total seasonal rate of
~0.062 lb ai/A.  The application rates used in the study correspond to
~1.4x and 1.1x the maximum proposed rates for applications at the
dormant and growing stages, respectively, and to ~1.4x the maximum
proposed seasonal rate.  Broadcast applications were made to the orchard
floor using ground equipment, in ~21-29 gal/A spray volumes with crop
oil concentrate as an adjuvant.  Samples of untreated and treated almond
nutmeat and hulls and pecan nutmeat were harvested at commercial
maturity, 55-60 days after the last application.

Nutmeat and hull samples were analyzed for residues of penoxsulam using
LC/MS/MS Method GRM 04.09.  The method is adequate based on acceptable
concurrent method recoveries.  The validated LOQ is 0.01 ppm for nutmeat
and hulls.

The storage durations for almond and pecan samples are reported in Table
4.  HED has concluded that the available storage stability data support
the storage conditions and durations of samples from the tree nut field
trials. 

The results of the tree nut field trials are summarized in Table 5. 
Residues of penoxsulam were nonquantifiable (<0.01 ppm) in/on all
samples of almond nutmeat, almond hull, and pecan nutmeat harvested
55-60 days following two soil broadcast applications of the 25 g/L OD
formulation at a total rate of 0.062-0.064 lb ai/A.

Conclusions.  The submitted grape and tree nut data are adequate to
satisfy data requirements.  Although a reduced number of trials was
conducted for each crop, ChemSAC previously determined (minutes of
1/24/2007 meeting) that reduced sets of residue trials for grape (four
trials) and tree nuts (six trials; three each for almonds and pecans)
would be adequate, provided no residues were detected, because the
proposed use is for soil application and penoxsulam is classified as a
reduced risk herbicide.

The use patterns used in the studies differed from the proposed use
patterns in that an OD formulation was used rather than an FlC
formulation, the individual application rates were slightly higher than
the maximum proposed rates, and the RTIs were longer than the proposed
RTIs.  Given that the formulation types are similar, the proposed use is
for soil application, and nonquantifiable residues were observed, HED
concludes that the crop field trial data adequately support the proposed
use patterns for grapes and tree nuts. 

Residues of penoxsulam were nonquantifiable (<0.01 ppm) in/on all
samples of grape, almond and pecan nutmeats, and almond hulls harvested
following soil treatment.  The submitted field trial data will support
the proposed tolerances at the LOQ of 0.01 ppm for residues of
penoxsulam in/on grape, the tree nut crop group, almond hulls, and, by
translation of the almond data, pistachio.

860.1520 Processed Food and Feed

DER Reference:	47444403.de2.doc

Dow AgroSciences has submitted a processing study for penoxsulam on
grape.  In a single crop field trial conducted in NY during the 2007
growing season, two soil applications were made with a 25 g/L OD
formulation of penoxsulam.  The first application was made near the end
of the grape vine dormant stage (bud swell) at 0.180 lb ai/A, and the
second application was made 81 days later, during the growing stage, at
0.090 lb ai/A, for a total seasonal rate of 0.270 lb ai/A (~5.8x the
proposed maximum seasonal rate).  Broadcast applications were made to
the vineyard floor using ground equipment, in ~20 gal/A spray volumes
with crop oil concentrate as an adjuvant.  Mature grapes were harvested
60 days after the second application and processed into juice and
raisins using procedures simulating commercial practices.

Grape, grape juice, and raisin samples were analyzed for residues of
penoxsulam using LC/MS/MS Method GRM 04.09.  The method was adequate
based on acceptable concurrent method recoveries.  The validated LOQ was
0.01 ppm for grape, juice, and raisin.

The storage durations for grape, juice, and raisin samples are reported
in Table 4.  The storage stability data submitted in conjunction with
the subject petition for grape adequately support storage conditions and
durations of RAC samples from the grape processing study.  No storage
stability data are available for grape processed commodities.

Residues of penoxsulam were nonquantifiable (<0.01 ppm) in/on grape
following two soil broadcast applications of the 25 g/L OD formulation
of penoxsulam, made at the end of dormancy and during the growing stage,
for a total rate of 0.270 lb ai/A (5.8x the proposed seasonal
application rate).  Following processing, residues of penoxsulam were
also nonquantifiable in grape juice and raisin.  Because residues were
nonquantifiable in both the RAC and the processed fractions, no
processing factors could be calculated.

The theoretical concentration factor for grape juice, based on
separation into components, is 1.2x, and the theoretical concentration
factor for raisins, based on loss of water, is 4.7x (OPPTS 860.1520,
Tables 2 and 3).

Conclusions.  The submitted processing data for grape are acceptable to
satisfy data requirements.  Residues of penoxsulam were nonquantifiable
(<0.01 ppm) in grape harvested following soil treatment at 5.8x the
maximum proposed seasonal application rate or in the processed
commodities of juice and raisin; therefore, no tolerances are needed for
grape processed commodities.  Although no storage stability data are
available for grape processed commodities, no additional data will be
required because no quantifiable residues of penoxsulam were observed
in/on grapes following treatment at a 5.8x exaggeration rate.

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

Analytical standards for penoxsulam and its stable isotope (as well as
metabolites penoxsulam 2-amino-8-methoxy, penoxsulam 5,8-dimethyl, and
penoxsulam 5-hydroxy) are currently available in the EPA National
Pesticide Standards Repository (personal communication with Dallas
Wright, ACB, 10/2/08), with an expiration date of 3/8/2009.  

860.1850 and 860.1900 Confined and Field Accumulation in Rotational
Crops

Because grapes and tree nuts are not rotated, no data pertaining to
rotational crops and no rotational crop restrictions are required to
support the proposed uses.  

860.1550 Proposed Tolerances

PP#5F7012; DP# 326985, 1/30/07, D. Soderberg

Tolerances are currently established for penoxsulam under 40 CFR
§180.605 and are expressed in terms of penoxsulam per se.  The
tolerance expression proposed by Dow AgroSciences is consistent with 40
CFR §180.605.

There are no Codex, Canadian, or Mexican MRLs established for residues
of penoxsulam in crops associated with this petition.  However, the
petitioner noted that registration has been requested on grapes in
France with a proposed MRL of 0.01 ppm (based on the analytical method
LOQ).

Adequate field trial data are available for grape and tree nuts.  The
data were not entered into the Agency’s tolerance spreadsheet as
specified by the Guidance for Setting Pesticide Tolerances Based on
Field Trial Data SOP because penoxsulam residues were nonquantifiable
in/on all samples.  The available field trial data will support the
proposed tolerances at the method LOQ of 0.01 ppm for penoxsulam in/on
grape, the tree nut crop group, and almond hulls.  No residue data were
submitted for pistachio; however, the available data for almond may be
translated to pistachio, and will support the proposed tolerance of 0.01
ppm.

The grape processing study demonstrated that no tolerances are needed
for grape juice or raisin to support the proposed use on grape. 

The proposed uses on grapes and tree nuts would result in a minimal
contribution to the dietary burden for dairy cattle only of 0.001 ppm
based on use on almond hulls.  As concluded previously (PP#5F7012), no
tolerances are required for residues of penoxsulam in livestock
commodities pending submission of a study on the magnitude of the
residue in irrigated crops.

A summary of the recommended tolerance for the current petition is
presented in Table 6.  The proposed tolerances should be revised to
reflect the correct commodity definition cited in Table 6. 

Table 6. 	Tolerance Summary for Penoxsulam.

Commodity	Proposed Tolerance (ppm)	Established Tolerance (ppm)
Recommended Tolerance (ppm)	Comments; 

Correct Commodity Definition

Almond, hulls	0.01	--	0.01

	Grape	0.01	--	0.01

	Nuts, tree, group 14	0.01	--	0.01	Nut, tree, group 14

Pistachio	0.01	--	0.01	At this time, pistachio is not part of the tree
nut crop group and a separate tolerance should be established.

References

DP#:		303172

Subject:	PP# 3F6542.  New Chemical - Penoxsulam (XDE-638) in/on Rice. 
Request for Petition Method Validation.

From:		W. Cutchin

To:		F. Siegelman

Dated:		7/19/04

MRIDs:	45830714 and 45830715

DP#:		288152

Subject:	Penoxsulam.  Petition for the Establishment of Permanent
Tolerances for the Use on Rice.  Summary of Analytical Chemistry and
Residue Data.  PP#3F6542.

From:		W. Cutchin

To:		P. Errico/J. Miller

Dated:		8/11/04

MRIDs:	45830712-17, 45830719-20, and 46267601

DP#:		328689

Subject:	Penoxsulam.  Frozen Storage Stability of XDE-638 (Penoxsulam)
in Rice (Raw Agricultural Commodities:  Grain, Straw, and Immature
Forage) and its Processed Products (Bran, Hulls, and Polished Rice).

From:		D. Soderberg

To:		P. Errico/J. Miller

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Dated:		12/18/06

MRIDs:	46449901

DP#:		326985

Subject:	Penoxsulam.  Section 3 Registration Application for Use of
GF-443 SC in Aquatic Sites and Request for a Tolerance Exemption
(PP#5F7012) on Fish and Shellfish.  Summary of Analytical Chemistry and
Residue Data.

From:		D. Soderberg

To:		J. Miller

Dated:		1/30/07

MRIDs:	46703504-07, and 46703509

  SEQ CHAPTER \h \r 1 Attachments:  

International Residue Limit Status sheet

Appendix I - Chemical Name and Structure Table

Template Version September 2005



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 
2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]
pyrimidin-2-yl)-6-(trifluoromethyl) benzenesulfonamide	Common Name:
Penoxsulam	X Proposed tolerance

□ Reevaluated tolerance

□ Other	Date: 10/01/08

Codex Status (Maximum Residue Limits)	U. S. Tolerances

X No Codex proposal step 6 or above

□ No Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#8F7369

DP#:  355914

Other Identifier:  

Residue definition (step 8/CXL): N/A	Reviewer/Branch:  M. Doherty/RAB2

	Residue definition:  penoxsulam per se

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Almond, hulls	0.01

Grape	0.01

Nuts, tree, group 14	0.01

Pistachio	0.01

	Limits for Canada	Limits for Mexico

X No Limits

□ No Limits for the crops requested	X No Limits

□ No Limits for the crops requested

Residue definition:  N/A

	Residue definition:  N/A

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

	Notes/Special Instructions:  S.Funk, 10/02/2008.

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APPENDIX I.	Chemical Names and Structures of Penoxsulam and
Metabolites.  

Common name;

Penoxsulam-5-OH;

Penoxsulam-5,8-DiOH;

Di-OH XDE-638	2-(2,2-difluoroethoxy)-N-

Page   PAGE  1  of   NUMPAGES  20 

Penoxsulam	Summary of Analytical Chemistry and Residue Data	DP#:  355914