UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC  20460

OFFICE OF PREVENTION,

PESTICIDES AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:	6 November 2009

SUBJECT:	Nicosulfuron:  Petition   SEQ CHAPTER \h \r 1 Requesting
Establishment of Permanent Tolerances (Associated with Section 3
Registration) for Residues Resulting from New Food/Feed Use of the
Herbicide on Grasses.  Summary of Analytical Chemistry and Residue Data.

Pastora™



FROM:	William T. Drew, Chemist  SEQ CHAPTER \h \r 1 

		Risk Assessment Branch 2 (RAB2)

		Health Effects Division (HED), 7509P

THRU:	Douglas Dotson, Chemist

		RAB2/HED, 7509P

TO:		Mindy Ondish and James Tompkins, RM Team 25

		Herbicide Branch (HB)

		Registration Division (RD), 7505P

  SEQ CHAPTER \h \r 1 This residue chemistry summary document was
originally prepared under contract by Dynamac Corporation (1901 Research
Boulevard, Suite 220; Rockville, MD 20850).  It has been reviewed by the
Health Effects Division (HED), and revised to reflect current Office of
Pesticide Programs (OPP) policies.  

Executive Summary

	Nicosulfuron, with CAS name 2-[[[[(4,6-dimethoxy-2-pyrimidinyl) amino]
carbonyl] amino] sulfonyl]-N,N-dimethyl-3-pyridinecarboxamide, is a
member of the pyrimidinylsulfonylurea family of herbicides.  It is
currently registered to DuPont Crop Protection for use on corn, at a
maximum seasonal rate of 0.063 pounds of active ingredient per acre (lb
ai/A); DuPont has previously indicated that they intended to propose a
new use on sorghum.  A Tolerance Reassessment Progress and Risk
Management Decision (TRED) was issued for nicosulfuron in December 2004,
and the HED Chapter of the Reregistration Eligibility Decision (RED) was
issued on 30 November 2004 (D302694; D. Hrdy).  

	DuPont has submitted a petition (PP#8F7501) proposing the establishment
of tolerances for residues of nicosulfuron in or on the raw agricultural
(and livestock) commodities (RACs) listed below.  

Grass, forage………………………………………………..
9.0 ppm

Grass, hay…………………………………………………	25.0
ppm

Cattle, fat………………………………………………….
0.05 ppm

Cattle, meat byproducts…………………………………...	0.05
ppm

Cattle, meat……………………………………………….	0.05
ppm

Goat, fat…………………………………………………...
0.05 ppm

Goat, meat byproducts…………………………………….	0.05
ppm

Goat, meat………………………………………………...	0.05
ppm 

Hog, fat……………………………………………………
0.05 ppm

Hog, meat byproducts……………………………………..	0.05
ppm

Hog, meat…………………………………………………	0.05
ppm 

Horse, fat………………………………………………….
0.05 ppm

Horse, meat byproducts…………………………………...	0.05
ppm

Horse, meat………………………………………………..	0.05
ppm 

Milk……………………………………………………….
0.05 ppm

Milk, fat…………………………………………………...
0.02 ppm

Sheep, fat………………………………………………….
0.05 ppm

Sheep, meat byproducts…………………………………...	0.05
ppm

Sheep, meat……………………………………………….	0.05
ppm

	In conjunction with the subject petition, DuPont is requesting Section
3 Registration for a 56.2% (by weight) dry flowable (DF) formulation of
nicosulfuron (Pastora™ Herbicide; EPA File Symbol 352-IRO).  This
product is a multiple active ingredient (MAI) formulation which also
contains metsulfuron-methyl at 15% (by weight).  The product is proposed
for multiple foliar applications to Bermuda grass and hay meadows, and
to switchgrass at single application rates of 0.035-0.053 lb ai/A, and a
maximum seasonal application rate of 0.088 lb ai/A.  A 0-day pre-harvest
interval (PHI) is proposed for grass forage and hay.  No re-treatment
interval (RTI) was specified.  The subject review only addresses the
adequacy of the available data to support the proposed uses of
nicosulfuron; the adequacy of available or concurrently submitted data
to support the proposed uses of metsulfuron-methyl is not addressed
herein.  

	Tolerances for residues of nicosulfuron are currently established under
40CFR §180.454, and are expressed in terms of the parent compound,
nicosulfuron.  Tolerances are established at 0.1 ppm in or on field and
sweet corn commodities.  No tolerances in livestock commodities have
been established.  

	The nature of the residue in plants is adequately understood for
purposes of this petition, based on a previously submitted corn
metabolism study, and the canola metabolism study reviewed herein.  RAB2
has concluded that the residue of concern (ROC) for tolerance
enforcement, and risk assessment in grass forage and hay is the parent
compound, nicosulfuron.  

	The nature of the residue in livestock is adequately understood for
purposes of this petition, based on an acceptable goat metabolism study.
 Based on the available data, the ROC for tolerance enforcement, and
risk assessment in milk and ruminant tissues is the parent compound,
nicosulfuron.  Because there are no significant poultry feed items
associated with grasses, a poultry metabolism study is not required to
support the proposed use.  There is no reasonable expectation of finite
residues of nicosulfuron in poultry commodities (40CFR §180.6[a][3]),
based on the registered uses on poultry feed items.  

	DuPont has proposed high performance liquid chromatography with tandem
mass spectrometric detection (HPLC/MS/MS) methods for the determination
of residues of nicosulfuron in grass forage and hay (DuPont-17928), and
livestock commodities (DuPont-17927).  Both methods determine residues
of metabolite IN-V9367 separately.  The method limit of quantitation
(LOQ) is 0.010 ppm for each analyte in all matrices.  For method
DuPont-17928 to be suitable for enforcement purposes, the petitioner
should modify the method to incorporate the changes identified by the
method developer, as well as those recommended by the independent
laboratory validation (ILV) lab, and submit an updated version of the
method.  For method DuPont-17927 to be suitable for enforcement
purposes, supporting raw data for method validation in eggs should be
submitted.  In addition, the petitioner should modify the method to
incorporate the changes made during the ILV.  RAB2 has concluded that
tolerance method validation (TMV) is not needed for either method.  When
the updated versions of the methods have been received, they will be
forwarded to the Food and Drug Administration (FDA) for inclusion in the
Pesticide Analytical Manual Volume II (PAM-II).  The proposed
enforcement methods (or an identical method) were used for data
collection in the submitted crop field trial and cow feeding studies.  

	Multiresidue methods testing data were previously submitted for
nicosulfuron, which indicated that the methods are not applicable to
nicosulfuron determination.  

	A livestock feeding study was submitted, reflecting dosing of lactating
dairy cows with nicosulfuron at target dose rates of 20, 50, 150 and 500
ppm in the diet.  RAB2 has concluded that the study is tentatively
acceptable, provided outstanding storage stability data for livestock
tissues confirm that residues of nicosulfuron and IN-V9367 are stable in
samples stored frozen for up to 9.4 months.  The data indicate that
tolerances are needed in milk, and the muscle and fat of cattle, goat,
horse and sheep at the LOQ of 0.01 ppm, and in meat byproducts at 0.05
ppm.  A tolerance is not needed in milk fat because residues did not
concentrate in cream.  Tolerances are not needed in hog commodities
because there are no swine feed items associated with the proposed use
on grasses, and the dietary burden to swine (resulting from use on corn)
is low enough that there is no reasonable expectation of finite residues
in hog commodities (40CFR §180.6[a][3]).  

	Pending submission of additional storage stability data for grass
forage and hay, and a residue decline study for grass conducted
according to the maximum proposed use pattern on grasses, adequate crop
field trial data have been submitted to support the requested use on
grasses.  The submitted data support the proposed tolerances for
residues of nicosulfuron in grass forage at 9.0 ppm, and in grass hay at
25 ppm.  It was noted that the submitted data are sufficient, with
respect to the number of field trials, varieties used, and residues
found by variety, to support crop group tolerances in group 17, grass
forage, fodder and hay.  

	The nature of the residue in rotational crops is adequately understood,
based on an acceptable confined rotational crop study reflecting
application at 0.062 lb ai/A.  HED concluded that the ROC in rotated
crops is the parent compound, nicosulfuron.  A 10-month plant-back
interval (PBI) was originally  recommended, based on phytotoxic effects,
and the PBI for soybeans was refined, based on a limited field
rotational crop study on soybeans only, reflecting application at 0.063
lb ai/A.  

	The petitioner has proposed rotational crop restrictions that are
consistent with, or more restrictive than, those established for use of
nicosulfuron on corn, using maximum application rates (0.070 lb ai/A)
that are consistent with the maximum registered use rate on corn (0.063
lb ai/A), and not the proposed maximum use rate on grasses (0.088 lb
ai/A).  RAB2 does not believe these restrictions are practical.  In
consideration of the expanded use of nicosulfuron on grasses, RAB2 now
requires submission of a limited rotational crop study, in order to
determine whether residues of nicosulfuron will occur in rotational
crops under actual field conditions, and to establish appropriate
rotational crop restrictions based on the maximum use pattern.  The
limited rotational crop trials should be conducted, as specified under
OPPTS Residue Chemistry Test Guideline 860.1900, on representative crops
of root and tuber vegetables, leafy vegetables or soybean, and small
grains, and should reflect an application rate of 0.088 lb ai/A.  

	No Codex or Mexican Maximum Residue Limits (MRLs) have been
established; Canadian MRLs are established in blueberries and corn, and
are expressed in terms of nicosulfuron.  

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

	RAB2 has examined the residue chemistry database for nicosulfuron. 
Pending submission of a revised Section B (see requirements under
Directions for Use), revised enforcement methods (see requirements under
Residue Analytical Methods), a revised Section F (see requirements under
Proposed Tolerances), and an analytical reference standard for
nicosulfuron (see requirements under Submittal of Analytical Reference
Standards), there are no residue chemistry issues that would preclude
granting conditional registration for the requested use of nicosulfuron
on grasses, nor the establishment of permanent tolerances for residues
of nicosulfuron in or on grass and livestock commodities.  Provided that
the associated human health risk assessment (D360807; M.A. Doherty; 27
October 2009) does not identify any issues of concern, the submitted
data support tolerances for residues of nicosulfuron, including its
metabolites and degradates, in or on grass and livestock commodities, at
the levels listed below.  Compliance with the tolerance levels specified
below is to be determined by measuring nicosulfuron only.  

Grass, forage	9.0 ppm

Grass, hay	25 ppm

Cattle, fat	0.01 ppm

Cattle, meat byproducts	0.05 ppm

Cattle, meat	0.01 ppm

Goat, fat	0.01 ppm

Goat, meat byproducts	0.05 ppm

Goat, meat	0.01 ppm 

Horse, fat	0.01 ppm

Horse, meat byproducts	0.05 ppm

Horse, meat	0.01 ppm 

Milk	0.01 ppm

Sheep, fat	0.01 ppm

Sheep, meat byproducts	0.05 ppm

Sheep, meat	0.01 ppm

A list of deficiencies, as noted elsewhere in this document, is
presented below.  

	860.1200 Directions for Use

The petitioner should amend the proposed label to specify an RTI; the
submitted field trial data support a minimum RTI of 16 days for
applications to grasses.  

The petitioner should revise the rotational crop restrictions to reflect
the maximum proposed seasonal use rate on grasses of 0.088 lb ai/A.  

	860.1340 Residue Analytical Methods

	Plant Commodities

For method DuPont-17928 to be suitable for enforcement purposes, the
petitioner should modify the method to incorporate the changes
identified by the method developer, as well as those recommended by the
ILV laboratory, and submit an updated version of the method.  

	Livestock Commodities

For method DuPont-17927 to be suitable for enforcement purposes,
supporting raw data for method validation in eggs should be submitted. 
In addition, the petitioner should modify the method to incorporate the
changes made during the ILV.  

	860.1550 Proposed Tolerances

The registrant should submit a revised Section F, so that the 40CFR
section referenced therein reflects the correct section for
nicosulfuron, §180.454.  

The proposed tolerances in milk, and in the meat and fat of ruminants,
should be reduced from 0.05 ppm to 0.01 ppm, and incorporated in the
revised Section F.  

The proposed tolerances in milk fat, and in hog fat, meat and meat
byproducts are unnecessary, and should not be included in the revised
Section F.  

	Note to PM:  According to HED’s Interim Guidance on Tolerance
Expressions (S. Knizner, 27 May 2009), the tolerance expression for
nicosulfuron cited in 40CFR §180.454 should be revised to state:  

Tolerances are established for residues of nicosulfuron, including its
metabolites and degradates, in or on the commodities listed in the table
below.  Compliance with the tolerance levels specified below is to be
determined by measuring only nicosulfuron
(2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,N-d
imethyl-3-pyridinecarboxamide).  

	RAB2 recommends that conditional registration for the requested use on
grasses be converted to unconditional registration upon submission of
the residue chemistry data listed below.  

	860.1380 Storage Stability

	Grass Forage and Hay

The petitioner should submit the final concurrent storage stability
report, reflecting storage stability of nicosulfuron and IN-V9367 in
grass forage and hay stored frozen for intervals of up to 9.6 and 12.4
months, respectively.  

	Livestock Tissues

The petitioner should submit the outstanding storage stability study,
reflecting storage stability of nicosulfuron and IN-V9367 in livestock
tissues stored frozen for intervals of up to 9.4 months.  

	860.1500 Crop Field Trials

A single residue decline trial with grass should be submitted.  The
trial should be conducted according to the maximum proposed use pattern
on grasses.  

	860.1900 Field Accumulation in Rotational Crops

In consideration of the expanded use of nicosulfuron on grasses, RAB2
now requires submission of a limited rotational crop study, in order to
determine whether residues of nicosulfuron will occur in rotational
crops under actual field conditions, and to establish appropriate
rotational crop restrictions based on the maximum use pattern.  The
limited rotational crop trials should be conducted, as specified under
OPPTS Residue Chemistry Test Guideline 860.1900, on representative crops
of root and tuber vegetables, leafy vegetables or soybean, and small
grains, and should reflect an application rate of 0.088 lb ai/A.  

Background

	Nicosulfuron is a member of the pyrimidinylsulfonylurea family of
herbicides, which includes, among others, halosulfuron, pirimisulfuron
and chlorsulfuron.  Nicosulfuron is used for control of weeds such as
Johnsongrass, quackgrass, foxtails, shattercane, panicums,
barnyardgrass, sandbur, pigweed and morning glory.  It is currently
registered to DuPont for use on corn, at a maximum seasonal rate of
0.063 lb ai/A.  The mode of action for nicosulfuron is the inhibition of
the enzyme acetolactate synthase (ALS), leading to the disruption of
cell division and elongation in the plant.  

	The chemical structure and nomenclature of nicosulfuron, and the
physicochemical properties of the technical grade of nicosulfuron are
presented in Tables 1 and 2, respectively (below).  The chemical names
and structures of nicosulfuron and its transformation products are
presented in Appendix I.  

Table 1	Nicosulfuron Nomenclature.  

Chemical structure	

Common name	Nicosulfuron

Company experimental name	DPX-V9360

Molecular formula	C15H18N6O6S

Molecular weight	410.40

IUPAC name
2-[(4,6-dimethoxypyrimidin-2-ylcarbamoyl)sulfamoyl]-N,N-dimethylnicotina
mide;

1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-dimethylcarbamoyl-2-pyridylsulfonyl
)urea

CAS name
2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,N-di
methyl-3-pyridinecarboxamide

CAS registry number	111991-09-4

End-use product (EP)	56.2% DF formulation (Pastora™ Herbicide; EPA
File Symbol 352-IRO)



Table 2	Physicochemical Properties of Nicosulfuron.  

Parameter	Value	Reference

Melting point/range	183.3 ± 0.3°C	MRID #47632204

pH	4.5	MRID #47632204

Density	1.441 ± 0.006 g/cm3 relative density	MRID #47632204

Water solubility (at 25°C)	Anhydrous form (g/L)

pH 5 = 0.36

pH 7 = 12.2

pH 9 = 39.1	Monohydrate form (g/L)

pH 5 = 0.42

pH 7 = 7.4

pH 9 = 47.96	MRID #47632204

Solvent solubility (at 28°C)	Solubility 		g/L

Acetone			18

Acetonitrile		23

Benzene			1.7

Chloroform		64

Dichloromethane		160

Dimethylformamide	64

Ethanol			4.5

Ethyl acetate		3.8

Hexane			<0.02

Methanol		0.44

2-Propanol		1.2

Tetrahydrofuran		26

Toluene			0.37

Xylenes			0.2	MRID #47632204

Vapor pressure (at 25°C)	1.2 x 10-16 Torr	MRID #47632204

Dissociation constant, pKa	4.22	MRID #47632204

Octanol/water partition coefficient, KOW (at 25°C)	pH 5 = 0.44

pH 7 = 0.02

pH 9 = 0.007	MRID #47632204

UV/visible absorption spectrum (at 20°C)	No absorbance maxima at or
above 290 nm for acidic, basic or neutral solutions.  	MRID #47632204



860.1200 Directions for Use

	DuPont has submitted a draft label (dated December 2008) for the 56.2%
DF formulation (Pastora™ Herbicide; EPA File Symbol 352-IRO).  The
product is an MAI formulation which also contains metsulfuron-methyl at
15%.  The proposed use directions are summarized in Table 3 (below).  

Table 3	Summary of Directions for Use of Nicosulfuron.  

Application Timing; Type; Equipment	Formulation

[EPA File Symbol]	Use Rate

(lb ai/A)	Max. Uses per Season	Max. Seasonal Use Rate

(lb ai/A)	PHI

(Days)	Use Directions and Limitations1

Bermuda Grass Pastures and Hay Meadows

Post-emergence;

≥10 GPA 2) or aerial (≥2 GPA)	56.2% DF

[352-IRO]	0.035-0.053	Not specified	0.088	0 3	Application is to be made
to Bermuda grass that has been established for at least one growing
season, when broadleaf weeds are <4” and grass weeds are <2” tall or
in diameter.  Use of a spray adjuvant is required (NIS at 0.25%-0.5%
v/v, or COC at 1-2% v/v, or a combination adjuvant containing NIS, COC,
and/or ammonium sulfate or urea/ammonium nitrate fertilizer).  

Switchgrass Grown in Tennessee

Post-emergence;

 ground (≥10 GPA) or aerial (≥2 GPA)	56.2% DF

[352-IRO]	0.035	2	0.070

(implied)

0.088

(general restriction)	0 3	Application is to be made after the
switchgrass has reached the 2-leaf stage, when weeds are young and
actively growing.  Use of an NIS is required.

1. NIS = Non-Ionic Surfactant.  COC = Crop Oil Concentrate.  

2. GPA = Gallons Per Acre.  

3. The label states that there are no grazing or haying restrictions.  

	Application through any type of irrigation system, or to grasses grown
for seed is prohibited.  No RTIs are specified.  Use is prohibited in
the Colorado counties of Alamosa, Conejos, Costilla, Rio Grande, and
Saquache.  A 4-hour re-entry interval (REI) is specified.  

	The label states that the 56.2% DF formulation should not be used on
soils having pH ≥7.9 because extended soil residual activity could
extend crop rotation intervals beyond normal.  The following rotational
crop restrictions are specified for all crop areas:  

1. A 4-month PBI for wheat (except durum), Bermuda grass, bluegrass,
ryegrass and tall fescue following application of the 56.2% DF
formulation at up to 0.070 lb ai/A.  

2. A 10-month PBI for durum wheat, barley and oats following application
at up to 0.053 lb ai/A.  

3. And, a 12-month PBI for alfalfa, and red, white and sweet clover
following application at up to 0.070 lb ai/A.  

≤7.0 following application of the 56.2% DF formulation at up to 0.035
lb ai/A:  

1. A 6-month PBI for sulfonylurea-tolerant (STS) soybeans.  

2. And, a 12-month PBI for field corn.  

The label further notes that a field bioassay should be completed before
rotating to any crop or grass species/variety not listed, or if the soil
pH is not in the specified range.  

	The label states that the product may be tank mixed with insecticides,
fungicides and other herbicides.  No tank mix partners are specified for
insecticides and fungicides; however, testing on small areas is
recommended, and tank mixing with malathion is prohibited.  The
herbicide tank mix partners specified are picloram, 2,4-D, dicamba,
triclopyr, triasulfuron and MCPA.  The label directions for the
companion herbicide are to be followed.  

	Conclusions:  The use directions are adequate to allow evaluation of
the residue data relative to the proposed use.  The submitted grass
field trials reflected foliar application at the maximum proposed
seasonal application rate, made as split applications (0.059 + 0.029 lb
ai/A), or as a single application.  Samples of grass forage and hay were
harvested at a 0-day PHI.  The growth stage at which applications were
made in the grass field trials is sufficiently representative of the
typical grass forage and hay stages to support the proposed use.  No
RTIs were specified.  The submitted field trial data support a minimum
RTI of 16 days for the requested use on grasses.  

	The proposed rotational crop restrictions are consistent with, or more
restrictive than, those established for use of nicosulfuron on corn. 
However, RAB2 does not believe that the application rate restrictions
associated with the recommended PBIs, all of which are lower than the
maximum proposed seasonal rate on grasses, are practical.  RAB2 has
concluded that additional field rotational crop data are now required to
support expanded use of nicosulfuron on grass (refer to section
860.1900).  When these data have been submitted, the petitioner should
revise the rotational crop restrictions to reflect the maximum proposed
seasonal rate on grasses of 0.088 lb ai/A.  The proposed rotational crop
restrictions may remain on the label until the required field rotational
crop data have been submitted, and more appropriate rotational crop
restrictions have been proposed.  

860.1300 Nature of the Residue - Plants

	DER for MRIDs #47632210 and 47632211 (Nature of the Residue in Canola)

	MRID #47632212 (Justification to Cite Existing Data, Reviewed Herein)

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	An acceptable corn metabolism study was previously submitted and
reviewed.  At that time, HED concluded that the ROC for risk assessment
and tolerance enforcement purposes in corn commodities is the parent
compound, nicosulfuron.  The results of the corn metabolism study are
summarized below for comparison purposes.  

	Per the HED Chapter of the RED, the Agency has expressed no
toxicological concern for the metabolites/degradates of nicosulfuron. 
The Agency concluded that, even if these other metabolites have toxicity
comparable to that of nicosulfuron, their dietary concentrations are so
low that their overall exposure and risk are not considered significant.
 

	In support of the requested use on grasses, DuPont has submitted a
metabolism study in canola (MRID #47632210), along with a justification
(MRID #47632212) to cite existing data to fulfill nature of the residue
data requirements in support of proposed tolerances on grass
commodities.  

 	Corn Summary:  Greenhouse-grown corn at the 4- to 5-leaf stage
received a single application of [pyridine-2-14C]-nicosulfuron or
[pyrimidine-2-14C]-nicosulfuron at 0.063 lb ai/A (0.7X the maximum
proposed seasonal application rate on grasses).  Samples of corn whole
plant were collected at PHIs of 0, 7, 14 and 30 days, silage samples
were collected at a PHI of 49 days, while grain, cob, and stalk (stover)
samples were collected at a PHI of 113 days (maturity).  

	Based on the results of the nicosulfuron metabolism study in corn, the
metabolism of nicosulfuron proceeds predominantly via two mechanisms,
which are (1) the hydrolysis of the sulfonylurea bridge yielding
pyridine sulfonamide (IN-V9367) and pyrimidine amine (IN-J290), and (2)
the hydroxylation of nicosulfuron at the 5-position (IN-70940) of the
pyrimidine amine followed by glucosidation (in early forage samples). 
The glucose conjugate, and its aglycone were present in the whole plant
(49-day PHI), but were not present in the fodder or stover (113-day
PHI).  The grain and cob (113-day PHI) were not analyzed because these
contained <0.005 ppm total [14C]-equivalents of nicosulfuron.  Pyridine
sulfonamide was present in the whole plant (0- to 30-day PHI), in silage
(49-day PHI), and fodder and stover (113-day PHI).  

	The analyses showed that nicosulfuron gradually decreased during the
corn growing season, and was present in very low levels at maturity. 
However, residues of IN-V9367 began at day 0, and were detected in the
whole plant and stalk at maturity (113-day PHI).  These residues were
higher than the detected residues of the nicosulfuron.  IN-J290 was
further metabolized to IN-70940 and its glucoside, but these metabolites
were not detected in the whole plant (49-day PHI), or in fodder or
stover (11-day PHI).  

	Canola (MRIDs #47632210 and 47632211):  DuPont has submitted a study
investigating the metabolism of [pyridine-2-14C]-nicosulfuron (specific
activity 62.9 µCi/mg) and [pyrimidine-2-14C]-nicosulfuron (specific
activity 62.2 µCi/mg) in canola.  Each radiolabeled test substance was
isotopically diluted with nonlabeled nicosulfuron, then formulated as a
75% DF formulation using formulation blank in water; an NIS was added at
0.5% v/v.  Each formulated test substance was applied to canola plants,
grown in pots in the greenhouse, at the early flowering stage, as a
single foliar broadcast application.  Applications were made at a
nominal rate of 0.026-0.027 lb ai/A, and at an exaggerated rate of 0.085
lb ai/A (pyridine label) or 0.079 lb ai/A (pyrimidine label).  The
exaggerated application rates used in the study are roughly 1X the
maximum proposed seasonal rate on grasses.  

	Immature canola plants were harvested immediately after application (0
days), and at 10 and 30 days after application.  Mature plants were
harvested at 96 days (pyridine label) and 93 days (pyrimidine label)
after application, and were separated into foliage, pods and seeds.  The
petitioner stated that mature plants were allowed to dry down for
approximately 10 days before the final harvest.  The in-life and
analytical phases of the study were conducted by E.I. du Pont de Nemours
and Company (Wilmington, DE).  

	Total radioactive residues (TRR) in canola matrices, determined by
summing extractable and non-extractable radioactivity, were 0.125, 0.099
and 0.086 ppm in immature canola foliage, respectively, harvested 0, 10
and 30 days following application of [pyridine-2-14C]-nicosulfuron at
0.027 lb ai/A.  In mature canola matrices, TRR were 0.034 ppm in
foliage, 0.123 ppm in pods, and <0.010 ppm in seeds.  Following
application of [pyrimidine-2-14C]-nicosulfuron at 0.026 lb ai/A, TRR
were 0.137, 0.080 and 0.074 ppm, respectively,  in immature foliage
harvested 0, 10 and 30 days after treatment, and 0.018, 0.070, and
<0.010 ppm in mature foliage, pods and seeds, respectively.  

	Following exaggerated-rate treatments of the test substances at 0.085
lb ai/A (pyridine label) or 0.079 lb ai/A (pyrimidine label), TRR were
0.447, 0.287, and 0.285 ppm in pyridine-label 0-, 10- and 30-day
immature foliage, respectively, and 0.296, 0.159 and 0.249 ppm in
pyrimidine-label 0-, 10- and 30-day immature foliage, respectively.  In
mature matrices, TRR were 0.078, 0.238 and 0.014 ppm in pyridine-label
foliage, pods and seeds, respectively, and 0.055, 0.207 and 0.015 ppm in
pyrimidine-label foliage, pods and seeds, respectively.  Based on the
low residues in seeds, the petitioner concluded that residues of
nicosulfuron and its metabolites are not readily translocated to seeds. 


	It was noted that canola seed samples were not initially subjected to
extraction or characterization procedures (MRID #47632210) because TRR
were <0.010 ppm; however, based on preliminary results from the crop
field trials, the petitioner subsequently decided that further
investigation was required (MRID #47632211).  Only seed samples from the
exaggerated-rate treatments were further investigated.  

d for ≤13% TRR (≤0.032 ppm) in immature foliage (both labels and
rates).  In mature matrices following nominal-rate applications,
non-extractable residues for both labels accounted for 35-50% TRR
(0.009-0.012 ppm) in foliage, and 43-61% TRR (0.043-0.053 ppm) in pods;
seeds were not extracted.  Following exaggerated-rate applications,
non-extractable residues for both labels accounted for 42-53% TRR
(0.029-0.033 ppm) in foliage, 23-37% TRR (0.055-0.076 ppm) in pods, and
34-39% TRR (0.005-0.006 ppm) in seeds.  No further characterization of
non-extractable residues was attempted.  

	RAB2 concludes that the extraction procedures were adequate in
extracting the majority of residues from canola matrices.  Of the
matrices included in the study, only seeds are considered by HED to be a
significant food or feed item of canola.  

	Residues were identified, quantitated and confirmed by HPLC on two
different systems.  Although combustion results were not provided for
the original study, the petitioner stated that summed residues for
canola foliage and pods averaged 107% of TRR, as determined by
combustion/liquid scintillation counter (LSC).  In the second study,
accountabilities for seeds were 100-188%.  

abolite IN-70940, was a minor metabolite in foliage and pods, present at
≤7% TRR; its glucoside conjugate was identified in foliage and pods at
<1-22% TRR, with the highest residues being observed in 30-day immature
foliage (both labels and rates).  Remaining residues were characterized
as unknowns, and accounted for no more than 20% TRR, or 0.031 ppm, in
any matrix.  RAB2 concludes that the petitioner has adequately
identified the residues of nicosulfuron in canola matrices.  

	Initial analysis for canola foliage and pods was completed within 5.4
and 8.8 months of harvest, respectively.  Analysis for seeds was
completed within 17.8 months of harvest, and seed extracts were stored
for 40-43 days prior to analysis; the storage conditions for seed
extracts were not reported.  Supporting storage stability data are not
required for canola foliage because initial analysis was completed
within 6 months.  RAB2 concludes that no additional storage stability
data are required to support the sample storage duration for canola
pods, because the metabolite profiles were generally similar for mature
foliage and pods, despite the slightly longer storage duration for pods,
and because canola pods are not considered to be a significant food or
feed item.  The petitioner submitted limited storage stability data in
support of the storage durations for seed samples and extracts.  RAB2
will not require additional storage stability data for canola seeds,
because TRR in canola seeds were quite low at both treatment levels, and
the metabolite profiles obtained for seeds were similar to those
observed in foliage and pods, despite the long storage duration of seed
samples.  

	Based on the canola metabolism study, the petitioner proposed that
nicosulfuron was metabolized in canola primarily by hydrolytic cleavage
of the sulfonylurea linkage to form IN-V9367 and IN-J290.  Subsequent
demethylation of IN-J290 formed IN-H1043 and, possibly, other polar
components.  Other metabolic reactions include the hydroxylation at the
5’ position of the pyrimidine ring to form IN-70940, and conjugation
of IN-70940 with glucose to form the glucoside.  

	Justification to Cite Existing Data (MRID #47632212):  DuPont has
submitted a discussion in support of their argument that a metabolism
study on pasture grass is not needed to support the proposed use on
grasses.  The discussion addresses the following points:  

1. The metabolic pathway for nicosulfuron is similar in corn and canola;
metabolite levels were generally low (<0.010 ppm at 30 days after
application), except for residues of IN-70940 in immature foliage.  

2. Identified metabolites were not found to be active in DuPont’s
herbicidal, fungicidal and insecticidal screening.  

3. Significant unidentified metabolites in the corn study were
short-lived, generally decreasing to <0.010 ppm within 14 days of
application, and were generally more polar than the parent.  

≤0.010 ppm at the 30-day PHI in corn forage.  

6. And, as a member of the grass family (Graminaceae), corn is suitable
as a representative of forage and rangeland grasses.  

	Conclusions:  The available corn metabolism study, and the submitted
canola metabolism studies are adequate to satisfy data requirements. 
The studies demonstrate that metabolism of nicosulfuron is similar in
corn and canola.  RAB2 concurs with the petitioner that translation of
the data for corn and canola is appropriate to support the proposed use
on grasses.  HED has determined that, for purposes of the subject
petition, the ROC for tolerance enforcement, and risk assessment is the
parent compound, nicosulfuron.  The need for additional plant metabolism
studies to support future uses will be decided on a case-by-case basis. 


860.1300 Nature of the Residue - Livestock

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	An acceptable goat metabolism study was previously submitted.  A
poultry metabolism study was not required because, at the proposed
treatment rate for corn, grain contained no detectable residues of
nicosulfuron (<0.05 ppm) or any significant metabolites, as demonstrated
by the plant metabolism study.  

	The Agency has previously concluded that there was no reasonable
expectation of finite residues (40CFR §180.6[a][3]) of nicosulfuron in
livestock commodities, based on registered uses on livestock feed items.
 

	The results of the goat metabolism study are summarized hereafter.  Two
lactating goats were dosed orally via gelatin capsule for 3 consecutive
days with  [pyridine-2-14C]-nicosulfuron or
[pyrimidine-2-14C]-nicosulfuron at 60 ppm (approximately 4-14X the
dietary burden to cattle).  Samples of milk were collected daily.  The
animals were sacrificed within 24 hours of the final dose, and tissue
samples, including liver, kidney, fat and muscle, were collected.  

e ≤0.07 ppm; no liver sample was analyzed for the pyridine-label goat.
 The only matrix subjected to characterization and/or identification
procedures was pyrimidine-label liver.  HPLC analysis indicated that
>50% TRR was parent, while the remaining radioactivity consisted of
minor peaks, none present at >10% TRR.  

	The proposed metabolic pathway for nicosulfuron in goat, based
primarily on analysis of urine, indicated three mechanisms:  

1. Hydrolysis of the sulfonylurea bridge, to yield pyridine sulfonamide
(IN-V9367) and pyrimidine amine (IN-J290), both of which undergo
additional metabolism.  

2. N-demethylation and subsequent loss of sulfur dioxide, leading to the
cyclized compound that was identified as a “cyclized ipso compound.”
 

3. And, oxidation and conjugation at the 5-position of the pyrimidine
ring.  

	Conclusions:  The available ruminant metabolism study is adequate to
satisfy data requirements in support of the proposed use on grasses. 
Based on the available data, the ROC for tolerance enforcement, and risk
assessment in ruminant commodities is the parent compound, nicosulfuron.


	Because there are no significant poultry feed items associated with
grasses, a poultry metabolism study is not required to support the
proposed use.  There remains no reasonable expectation of finite
residues of nicosulfuron in poultry commodities (40CFR §180.6[a][3]),
based on the registered and proposed uses on poultry feed items.  

860.1340 Residue Analytical Methods

	DER for MRIDs #47632206 and 47632209 (Plant Commodities)

	DER for MRIDs #47632207 and 47632208 (Livestock Commodities)

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	Residue Chemistry Memo (DEBs #5324-5326 and 6501-6503; J. Stokes; 4 May
1990)

	Plant Commodities

	Enforcement and Data Collection Methods:  An HPLC enforcement
analytical method was previously submitted, and was subjected to a TMV
in conjunction with the established use on corn.  The method is listed
with an asterisk in the Index of PAM-II.  An asterisk indicates that the
method has been submitted to EPA but not compiled in PAM-II.  

	Under the current action, DuPont has submitted an HPLC/MS/MS method,
DuPont-17928, for the determination of residues of nicosulfuron and its
metabolite, IN-V9367, in grass forage and hay.  The method was used for
data collection in the grass field trial study submitted with this
petition.  DuPont is proposing this method as an enforcement method, and
has submitted method validation data, and an ILV of the method.  

	Briefly, samples of grass forage and hay are soaked in acetone/0.1M
ammonium carbonate (9:1, v:v) for 25-30 minutes, then extracted by
homogenization.  The mixture is centrifuged, and the supernatant is
filtered, then mixed with 0.1M ammonium carbonate.  The resulting
mixture is centrifuged and filtered, then brought to volume with
acetone.  Aliquots of the sample extracts are purified by sequential
solid-phase extraction (SPE) on Envi-Carb and hydrophilic-lipophilic
balanced (HLB) Oasis cartridges.  The analytes are not retained on the
Envi-Carb cartridge; residues are eluted from the Oasis cartridge with
methanol.  The purified eluates are evaporated to dryness under a stream
of nitrogen, and reconstituted in methanol/10mM ammonium formate (1:19,
v:v), then filtered for analysis by HPLC/MS/MS.  The method monitors two
ion transitions for each analyte.  The LOQ is 0.010 ppm for each analyte
in grass forage and hay.  

	The method was adequately validated, using samples of grass forage and
hay fortified at the method LOQ and 10X the LOQ (0.010 and 0.10 ppm). 
Recoveries from grass forage and hay were within the generally
recognized acceptable range of 70-120%.  Recovery ranges from grass
forage and hay, respectively, were 92-110% (with a mean of 99%, and
standard deviation of 4.8%), and 89-107% (with a mean of 97%, and
standard deviation of 6.3%) for nicosulfuron.  Recovery ranges from
grass forage and hay, respectively, were 73-114% (with a mean of 98%,
and standard deviation of 14.1%), and 80-106% (with a mean of 91%, and
standard deviation of 8.6%) for IN-V9367.  It was noted that the
fortification levels used in method validation were not adequate to
bracket expected residues in grass forage and hay.  However, the
fortification levels used in the method validation conducted
concurrently with the grass field trial study were adequate.  

	No confirmatory method was submitted.  The petitioner stated that
confirmation of any identified peak was based on detection and relative
ratio of its two parent-to-daughter ion transitions collected during
method validation.  The observed ion ratio of each fortified sample is
compared to the average of the ion ratios for the five calibration
standards used to generate the calibration curve.  For a sample set to
be valid, the relative standard deviation (RSD) of the ion ratios
calculated from the calibration standards should be less than 20%, and
the ion ratio for the analyte in question should fall within ±30% of
the average ratio for all calibration standards in the sample set.  

	No radiovalidation data were submitted with the method; however, the
petitioner cited previously submitted radiovalidation data generated in
conjunction with the corn metabolism study (MRID #41082626).  According
to the petitioner, extraction of corn matrices with acetone/0.1M
ammonium carbonate (9:1, v:v) released a minimum of 87.5% of the TRR
from corn forage (whole plant), and additional extraction of corn stover
with 0.1M ammonium carbonate released 60.0-67.8% of the remaining
non-extractable residues.  The results of the corn metabolism study are
summarized in the HED Chapter of the RED.  Although the extraction
efficiency data for corn were not specifically addressed, the results
reported above are consistent with the results of the canola metabolism
study, in which extraction with acetone/0.1M ammonium carbonate released
47-65% TRR from mature foliage, 39-77% TRR from pods, and 61-66% TRR
from seeds.  No additional radiovalidation data are required to support
the method.  

	A successful ILV of the enforcement method was submitted, reflecting
adequate recoveries from grass forage and hay fortified at the LOQ and
10X LOQ (0.010 and 0.10 ppm).  A number of revisions to the method were
identified by the method developer prior to initiation of the ILV, and
by the ILV laboratory during the conduct of the study.  These changes
have not yet been made to the method by the petitioner.  All of these
revisions should be incorporated into the method.  

	The method used for sample analysis in the grass field trials reflected
the changes recommended in conjunction with ILV of the method, in
addition to other minor modifications.  

	Conclusions:  The submitted data are tentatively adequate to satisfy
data requirements for residue analytical methods for grass commodities,
pending submission of additional supporting information.  RAB2 concludes
that method DuPont-17928 is acceptable for determination of
nicosulfuron, the ROC in plant commodities, as well as for determination
of metabolite IN-V9367.  For method DuPont-17928 to be suitable for
enforcement purposes, the petitioner should modify the method to
incorporate the changes identified by the method developer, and those
recommended by the ILV laboratory, and submit an updated version of the
method.  A TMV of the method is not needed, because the method was
adequately validated by the developing laboratory, by an independent
laboratory, and in conjunction with the grass field trials.  When the
updated version of the method has been received, it will be forwarded to
FDA for inclusion in the PAM-II.  

	Livestock Commodities

	Enforcement and Data Collection Methods:  DuPont has submitted an
HPLC/MS/MS method, DuPont-17927, for the determination of residues of
nicosulfuron and its metabolite, IN-V9367, in livestock commodities. 
The method was used for data collection in the cow feeding study. 
DuPont is proposing this method as an enforcement method, and has
submitted method validation data, and an ILV of the method.  

	Briefly, samples of milk, cream and eggs are mixed with water followed
by acetonitrile (ACN; 1:2, v:v), then centrifuged; the supernatant is
brought to volume with water.  Samples of livestock tissues (fat,
kidney, liver, and meat) are extracted with ACN/water (9:1, v:v), then
centrifuged; the supernatant is brought to volume with ACN/water.  The
resulting supernatants (all matrices) are evaporated to dryness under a
stream of nitrogen, then reconstituted in 10mM ammonium formate. 
Aliquots of the sample extracts are purified by SPE on an HLB Oasis
cartridge; residues are eluted with methanol.  The purified eluates are
evaporated to dryness under a stream of nitrogen, and reconstituted in
methanol/10 mM ammonium formate (1:19, v:v), then filtered for analysis
by HPLC/MS/MS.  Alternatively, extracts (without SPE clean-up) may be
filtered through 0.20- to 0.45-µm filters, diluted 20X with
methanol/5mM ammonium formate (1:19, v:v), and analyzed directly on a
sensitive HPLC/MS/MS system.  The method monitors two ion transitions
for each analyte.  The LOQ is 0.010 ppm for each analyte in livestock
commodities.  

	The method was adequately validated using samples of milk, cream, eggs,
and beef muscle, kidney, liver, and fat fortified at roughly the LOQ and
10X the LOQ (0.011 ppm and 0.11 ppm for nicosulfuron, and 0.012 and 0.12
ppm for IN-V9367); it was noted that only summary data were provided for
eggs.  Recoveries from livestock commodities were within the generally
recognized acceptable range of 70-120% for both analytes.  Using the
standard method procedures, overall recovery ranges from milk and
tissues were 77-111% (with a mean of 96%, and standard deviation of
8.4%) for nicosulfuron, and 82-112% (with a mean of 95%, and standard
deviation of 6.7%) for IN-V9367.  Using the alternative procedures,
overall recovery ranges from milk and tissues were:  86-105% (with a
mean of 96%, and standard deviation of 5.0%) for nicosulfuron, and
90-108% (with a mean of 101%, and standard deviation of 5.0%) for
IN-V9367.  From eggs, overall recovery ranges using the standard
procedures were 84-96% (with a mean of 89%, and standard deviation of
4.5%) for nicosulfuron, and 79-95% (with a mean of 84%, and standard
deviation of 3.2%) for IN-V9367.  Using the alternative procedures,
overall recovery ranges from eggs were 81-111% (with a mean of 91%, and
standard deviation of 8.4%) for nicosulfuron, and 84-107% (with a mean
of 94%, and standard deviation of 6.7%) for IN-V9367.  

	No confirmatory method was submitted.  The petitioner stated that
confirmation of any identified peak was based on detection and relative
ratio of its two parent-to-daughter ion transitions collected during
method validation.  The observed ion ratio of each fortified sample is
compared to the average of the ion ratios for the five calibration
standards used to generate the calibration curve.  For a sample set to
be valid, the RSD of the ion ratios calculated from the calibration
standards should be less than 20%, and the ion ratio for the analyte in
question should fall within ±30% of the average ratio for all
calibration standards in the sample set.  

	No radiovalidation data were submitted with the method; however, the
petitioner noted that the extraction procedure is based on the
extraction procedure used in the acceptable goat metabolism study (MRID
#41082627), in which a sample of liver from a goat dosed with
[pyrimidine-2-14C]-nicosulfuron was extracted with ACN/water (9:1, v:v).
 The results of the goat metabolism study are summarized in the HED
Chapter of the RED.  Milk samples from the goat metabolism study were
not subjected to extraction procedures.  No additional radiovalidation
data are required to support the method at this time; however, should a
poultry metabolism study be conducted in the future, additional
radiovalidation for eggs and tissues should be conducted.  

	A successful ILV of the enforcement method (alternate procedures) was
submitted reflecting adequate recoveries for milk, cow liver, and eggs
fortified at the LOQ and 10X LOQ (0.010 and 0.10 ppm).  It was noted
that a number of revisions to the method, mostly minor, were identified
prior to initiation of the ILV, and during the ILV.  Although none of
these changes was identified as critical by the ILV laboratory, RAB2
recommends that these changes be incorporated into the method.  

	Conclusions:  The submitted data are tentatively adequate to satisfy
data requirements for residue analytical methods for livestock
commodities, pending submission of additional supporting data and
information.  RAB2 concludes that method DuPont-17927 is acceptable for
determination of nicosulfuron, the ROC in livestock commodities, as well
as for determination of metabolite IN-V9367.  For method DuPont-17927 to
be suitable for enforcement purposes, supporting raw data for method
validation with eggs should be submitted.  In addition, the petitioner
should modify the method to incorporate the changes made during the ILV.
 A TMV of the method is not needed, because the method was adequately
validated by the developing laboratory, by an independent laboratory,
and in conjunction with the cow feeding study.  When the updated version
of the method has been received, it will be forwarded to FDA for
inclusion in the PAM-II.  

860.1360 Multiresidue Methods

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	Nicosulfuron was previously tested through the FDA Multi-Residue
Methods under the old Protocols I (current Protocols E and F), II, III
(current Protocol D), and IV (current Protocol A).  None of the
multiresidue methods was applicable to nicosulfuron.  These data were
forwarded to FDA.  The HED Chapter of the RED noted that nicosulfuron
should be recoverable by Protocol G, which was developed subsequent to
multiresidue methods testing for nicosulfuron.  

860.1380 Storage Stability

	Residue Chemistry Memo D338945 and D342602; A. Parmar; 18 October 2007

	Plant Commodities

	Storage stability data were previously submitted reflecting the
stability of residues of nicosulfuron in corn commodities.  The data
indicated that residues of nicosulfuron were relatively stable in sweet
corn (kernel plus cob with husk removed), and corn grain, stover and
forage for intervals of up to 12 months.  

	Samples of grass forage and hay from the submitted grass field trials
were stored frozen (at -20°C) for up to 293 days (9.6 months) and 377
days (12.4 months), respectively.  The petitioner has submitted interim
results for a concurrent storage stability study which indicate that
residues of nicosulfuron and IN-V9367 are stable in grass forage and hay
stored frozen for intervals of up to 91-92 days (3 months).  The
petitioner has indicated that a final report will be issued providing
data in support of the longest storage durations in the study.  

	Conclusions:  The available storage stability data for corn, reflecting
storage stability of the parent compound, nicosulfuron, are tentatively
adequate to support the grass field trial study, pending submission of
the outstanding concurrent storage stability data for grass forage and
hay.  Based on the available data, there are no storage stability
issues, and no corrections need be applied to the grass field trial
results.  

	The petitioner should submit the final concurrent storage stability
report, reflecting storage stability of nicosulfuron and IN-V9367 in
grass forage and hay stored frozen for up to 9.6 and 12.4 months,
respectively.  

	Livestock Commodities

	Samples from the cow feeding study were stored frozen (at roughly
-20ºC) from collection to analysis.  Maximum storage durations were 21
days for milk, cream and skim milk, and 287 days (approximately 9.4
months) for tissues.  Because milk samples were stored for less than 30
days, no supporting storage stability data are required.  The petitioner
stated that a storage stability study for nicosulfuron and IN-V9367 in
tissues is in progress, and will be submitted upon completion.  

	Conclusions:  No storage stability data are available reflecting the
storage stability of nicosulfuron or metabolite IN-V9367 in milk or
livestock tissues.  The petitioner should submit the outstanding storage
stability study, reflecting storage stability of nicosulfuron and
IN-V9367 in livestock tissues stored frozen for up to 9.4 months.  

860.1400 Water, Fish, and Irrigated Crops

	The proposed use is not relevant to this guideline topic.  

860.1460 Food Handling

	The proposed use is not relevant to this guideline topic.  

860.1480 Meat, Milk, Poultry, and Eggs

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	DER for MRID #47640501 (Magnitude of the Residue in Livestock)

	Feeding studies were not previously required for nicosulfuron in
support of the use on corn, because residues of nicosulfuron were near
or below the LOQ (<0.05 ppm) in corn forage, silage, fodder and grain
following application at 0.063 or 0.125 lb ai/A (1X or 2X the maximum
use rate on corn), nor in grain from the processing study following
application at 8X.  In the HED Chapter of the RED, HED concluded that
based on the LOQ, the goat metabolism study was conducted at a feeding
level of 1200X, and adequately represented an exaggerated feeding level.
 Measurable secondary residues of nicosulfuron were not expected in
livestock commodities as a result of the use on corn.  

	There are ruminant feedstuffs (grass forage and hay) associated with
the proposed use of nicosulfuron on grasses.  The dietary burdens of
nicosulfuron to livestock resulting from the proposed use on grasses,
and the established use on corn, based on maximum reasonably balanced
diets, are presented in Table 4 (below).  

Table 4	Calculation of Dietary Burdens to Livestock from Nicosulfuron
Residues.  

Feedstuff	Type 1	% Dry Matter 2	% Diet 2	Recommended Tolerance (ppm)
Dietary Contribution (ppm) 3

Beef Cattle

Grass hay	R	88	15	25	4.261

Field corn grain	CC	88	80	0.10	0.091

PC not registered	PC	--	5	--	--

TOTAL BURDEN	--	--	100	--	4.35

Dairy Cattle

Grass forage	R	25	45	9.0	16.200

Field corn grain	CC	88	45	0.10	0.051

PC not registered	PC	--	10	--	--

TOTAL BURDEN	--	--	100	--	16.25

Poultry

Field corn grain	CC	88	75	0.10	0.075

PC not registered	PC	--	25	--	--

TOTAL BURDEN	--	--	100	--	0.075

Swine

Field corn grain	CC	88	85	0.10	0.085

PC not registered	PC	--	15	--	--

TOTAL BURDEN	--	--	100	--	0.085

1. R = Roughage, CC = Carbohydrate Concentrate, PC = Protein
Concentrate.  

2. OPPTS Residue Chemistry Test Guideline 860.1000, Table 1 Feedstuffs
(June 2008).  

3. Contribution = ([tolerance ÷ %DM] x %diet) for beef and dairy
cattle.  Contribution = ([tolerance] x %diet) for 	poultry and swine.  

	DuPont has submitted a ruminant feeding study with nicosulfuron. 
Nicosulfuron was administered orally in gelatin capsules to four groups
of lactating dairy cows (3 cows/group), once daily for 29 consecutive
days, at target dosing levels of 20, 50, 150 and 500 ppm in the diet. 
Based on daily dry matter intake, the actual dosing levels were 19.63,
48.79, 146.89 and 489.20 ppm.  The dose rates correspond to roughly
4.5X, 11X, 34X and 112X the dietary burden to beef cattle, and roughly
1.2X, 3.0X, 9.0X and 30X the dietary burden to dairy cattle.  Two
additional cows were dosed at 500 ppm for 29 days, in order to
investigate depuration.  Two control cows received gelatin capsules
containing no nicosulfuron.  

	Milk was collected twice daily, and samples from the afternoon milking
were combined with samples from the next morning.  Milk samples from the
50-, 150- and 500-ppm groups collected on Days 1, 3, 7, 10 (150- and
500-ppm groups only), 14, 21 and 28 were analyzed.  Skim milk and cream
samples were prepared from milk collected on Days 14 and 21.  Milk
samples from the depuration group collected on Days 28, 29, 31, 33 and
35 were analyzed.  Cows from the four treatment groups were sacrificed
approximately 23-24 hours after the final dose.  One cow from the
depuration group was sacrificed on Day 33, when all residues in milk
were less than the limit of detection (LOD); the second cow from the
depuration group was sacrificed on Day 39.  Samples of liver, kidney,
muscle (round, flank and loin) and fat (omental, renal and subcutaneous)
were collected from all cows.  

	Samples of milk and tissues were analyzed for residues of nicosulfuron
and IN-V9367 using adequate HPLC/MS/MS methods, DuPont-17927 (milk,
cream and skim milk), or an ABC method 63236-MI (tissues).  The methods
are essentially identical.  The LOQs were 0.010 ppm for each analyte in
milk and tissues, and the LODs were 0.003 for each analyte in each
matrix.  Samples were stored frozen (at roughly -20ºC) from collection
to analysis; this duration was up to 21 days for milk, cream and skim
milk, and 287 days (9.4 months) for tissues.  Because milk samples were
stored for less than 30 days, no supporting storage stability data are
required.  No storage stability data are available to support the
storage durations and conditions for tissues; the petitioner stated that
a storage stability study for nicosulfuron and IN-V9367 in tissues is in
progress.  

	Residues of nicosulfuron and IN-V9367 were comparable in livestock
commodities.  Residues of IN-V9367 were higher than residues of
nicosulfuron in milk, cream, skim milk, and muscle, while residues of
nicosulfuron were higher than residues of IN-V9367 in remaining tissues
(liver, kidney and fat).  Detectable residues of nicosulfuron and
IN-V9367 were observed in milk, cream and skim milk at all feeding
levels examined (50, 150 and 500 ppm).  Residues of nicosulfuron and
IN-V9367 reached a plateau in milk within 7-10 days of dosing for all
dose groups.  Residues of nicosulfuron in milk (after plateau) were
<0.010-0.020, 0.016-0.032, and 0.11-0.14 ppm at dosing levels of 50, 150
and 500 ppm, respectively; corresponding residues of IN-V9367 were
0.013-0.024, 0.033-0.049, and 0.14-0.20 ppm.  Residues in cream and skim
milk were comparable to those in milk.  Residues of nicosulfuron in
cream and skim milk, respectively, were <0.010-0.010 and <0.010-0.012
ppm at the 50-ppm dosing level, 0.019-0.026 and 0.024-0.030 ppm at the
150-ppm dosing level, and 0.084-0.12 and 0.11-0.15 ppm at the 500-ppm
dosing level.  Corresponding residues of IN-V9367 were 0.011-0.016 and
0.014-0.019 ppm at the 50-ppm dosing level, 0.026-0.042 and 0.033-0.050
ppm at the 150-ppm dosing level, and 0.11-0.17 and 0.14-0.19 ppm at the
500-ppm dosing level.  

 were ≤0.010, 0.012-0.020, 0.030-0.038, and 0.14-0.15 ppm.  Residues
of nicosulfuron in kidney were 0.029-0.048, 0.063-0.16, 0.13-0.18, and
0.71-0.79 ppm at the 20-, 50-, 150- and 500-ppm feeding levels,
respectively; corresponding residues of IN-V9367 were 0.011-0.025,
0.038-0.069, 0.055-0.098, and 0.39-0.46 ppm.  In muscle, residues of
nicosulfuron were ≤0.010, <0.010-0.015, 0.017-0.024, and 0.052-0.065
ppm at the 20-, 50-, 150- and 500-ppm feeding levels, respectively;
corresponding residues of IN-V9367 were <LOQ, 0.010-0.016, 0.023-0.033,
and 0.089-0.11 ppm.  In fat, residues of nicosulfuron were <LOQ,
<0.010-0.011, <0.010-0.023, and 0.024-0.050 ppm at the four respective
dosing levels; corresponding residues of IN-V9367 were <LOQ, ≤0.010,
<0.010-0.014, and 0.022-0.046 ppm.  

	In the depuration study, reflecting dosing at 500 ppm, residues were
non-detectable in milk by sampling Day 31, and in tissues by sampling
Day 33.  

	Conclusions:  The submitted dairy cow feeding study is tentatively
acceptable, provided the outstanding storage stability data confirm that
residues of nicosulfuron and IN-V9367 are stable in tissues stored
frozen for intervals of up to 9.4 months.  The petitioner has indicated
that the storage stability study has been initiated.  Samples were
analyzed for residues of nicosulfuron, the ROC, as well as for residues
of metabolite IN-V9367, using an acceptable method.  

	The lowest dosing level corresponds to 1.2X the dietary burden to dairy
cattle, and the highest dosing level corresponds to 30X the dietary
burden to dairy cattle.  Detectable residues of nicosulfuron were
observed at feeding levels of 50, 150 and 500 ppm in milk, skim milk,
and cream, and in tissues at all feeding levels except in fat at the
20-ppm feeding level.  Residues did not concentrate in cream.  

	If the residues observed at the various dosing levels are adjusted to a
1X feeding level for dairy cattle (see Table 5, below), maximum expected
residues of nicosulfuron would be 0.007 ppm in milk, 0.013 ppm in liver,
0.053 ppm in kidney, 0.008 ppm in muscle, and 0.008 ppm in fat.  The
data indicate that tolerances are needed in milk, and in the muscle and
fat of cattle, goat, horse, and sheep at the LOQ of 0.01 ppm, and in
meat byproducts at 0.05 ppm.  A tolerance is not needed in milk fat,
because residues did not concentrate in cream.  

Table 5	Summary of Residue Data from Ruminant Feeding Study with
Nicosulfuron.  

Matrix	Maximum Residues (ppm) at Each Dosing Level	Residues Adjusted to
1X Feeding Level for Dairy Cattle*

	20	50	150	500	20	50	150	500

Nicosulfuron

Milk (Days 7-28)	--	0.020	0.032	0.14	--	0.007	0.004	0.005

Cream	--	0.010	0. 026	0.12	--	0.003	0.003	0.004

Skim milk	--	0.012	0.030	0.15	--	0.004	0.003	0.005

Liver	0.016	0.033	0.073	0.34	0.013	0.011	0.008	0.011

Kidney	0.048	0.16	0.18	0.79	0.040	0.053	0.020	0.026

Muscle	0.010	0.015	0.024	0.065	0.008	0.005	0.003	0.002

Fat	<0.010	0.011	0.023	0.050	0.008	0.004	0.003	0.002

IN-V9367

Milk (Days 7-28)	--	0.024	0.049	0.20	--	0.008	0.005	0.007

Cream	--	0.016	0.042	0.17	--	0.005	0.005	0.006

Skim milk	--	0.019	0.050	0.19	--	0.006	0.006	0.006

Liver	0.010	0.020	0.038	0.15	0.008	0.007	0.004	0.005

Kidney	0.025	0.069	0.098	0.46	0.021	0.023	0.011	0.015

Muscle	<0.010	0.016	0.033	0.11	0.008	0.005	0.004	0.004

Fat	<0.010	0.010	0.014	0.046	0.008	0.003	0.002	0.002

* The dose rate factors listed in the text above Table 5 (based on the
actual dosing levels) were used for calculating 	the adjusted residues
(1.2X, 3.0X, 9.0X and 30X).  

	Tolerances are not needed in hog commodities because there are no swine
feed items associated with the proposed use on grasses, and the dietary
burden to swine (resulting from use on corn) is low enough that there is
no reasonable expectation of finite residues in hog commodities (40CFR
§180.6[a][3]).  If the residues observed in liver, kidney, meat and fat
are adjusted to a 1X feeding level, maximum residues of 0.0003 ppm in
swine tissues (kidney) would be much lower than the LOD (0.003 ppm).  

	Because there are no poultry feed items associated with the proposed
use on grasses, no additional data for poultry are required at this
time.  

860.1500 Crop Field Trials

	DER for MRID #47632204 (Grass Field Trials)

	DuPont has submitted field trial data for nicosulfuron on grass. 
Twelve grass field trials were conducted in the United States in Zones 5
(IA, MO, ND, NE; 5 trials), 6 (OK, TX; 3 trials), 7 (SD; 1 trial), and 8
(OK, TX; 3 trials) during the 2007 growing season.  The trials reflected
application to the representative commodities of grass forage, fodder
and hay (group 17), which are Bermuda grass (five trials), brome grass
(four trials), and fescue (three trials).  

	At each test location, an untreated plot and two treated plots,
reflecting three separate treatment schemes, were established.  At each
plot, the 75% water-dispersible granule (WDG) formulation was applied to
grass at the boot stage (BBCH 41-50), as a foliar broadcast application,
using ground equipment, in spray volumes of 3.6-5.0 GPA at three trial
sites (to simulate aerial application), and in 12.2-20.1 GPA at the
remaining sites.  At one plot, the 75% WDG formulation was applied to
grass at the boot stage, at a target rate of 0.059 lb ai/A (Treatment
1a, roughly 0.7X the proposed maximum seasonal rate).  Grass samples
were harvested immediately after application (0 days), and the grass in
the plot was allowed to re-grow to boot stage, at which time a second
application was made, at a target rate of 0.029 lb ai/A, for a total
seasonal application rate of 0.088 lb ai/A (Treatment 1b, 1X rate). 
RTIs were 16-71 days.  At the second plot, the 75% WDG formulation was
applied as a single application to grass at the boot stage, at a target
rate of 0.088 lb ai/A (Treatment 2, 1X rate).  An NIS or COC was added
to the spray mixture for all applications at eight trial sites (except
that ammonium sulfate fertilizer was used instead of the NIS/COC for the
second application, Treatment 1b, at one site), and ammonium sulfate or
urea/ammonium nitrate fertilizer was added to the spray mixture instead
of the NIS/COC for all applications at four trial sites.  

	Samples of grass forage and hay were harvested at a 0-day PHI for each
treatment.  Hay samples were allowed to dry in the field for 2-8 days
before collection.  

	Samples of grass forage and hay were analyzed for residues of
nicosulfuron and IN-V9367 using an adequate HPLC/MS/MS method,
DuPont-17928.  The LOQ is 0.010 ppm for each analyte in grass forage and
hay.  Samples of grass forage and hay were stored frozen for durations
of up to 293 days (9.6 months) and 377 days (12.4 months), respectively.
 The available storage stability data for corn are tentatively adequate
to support the study, pending submission of outstanding concurrent
storage stability data for grass forage and hay.  

	The results of the grass field trial study are presented in Table 6,
below.  Following a single broadcast foliar application of the 75% WDG
formulation to grass at the boot stage at 0.056-0.061 lb ai/A, maximum
residues of nicosulfuron were 5.7 ppm in forage and 10 ppm in hay;
maximum residues of IN-V9367 in forage and hay were 0.28 and 0.93 ppm,
respectively.  Following two applications made immediately prior to the
first and second cuttings, for a total application rate of 0.085-0.091
lb ai/A, maximum residues of nicosulfuron in grass forage and hay from
the second cutting were 3.6 and 7.3 ppm, respectively; maximum residues
of IN-V9367 in forage and hay were 0.26 and 0.47 ppm, respectively. 
Following a single application to grass at the boot stage at 0.088-0.092
lb ai/A, maximum residues of nicosulfuron were 8.2 ppm in forage and 18
ppm in hay; maximum residues of IN-V9367 in forage and hay were 0.59 and
1.2 ppm, respectively.  

Table 6	Summary of Residue Data from Grass Field Trials with
Nicosulfuron (0.088 lb ai/A Total 		Use Rate, 0-day PHI).  

Crop Matrix	Treatment;

Total Use Rate

(lb ai/A)	PHI 1 (Days)	Residue Levels

(ppm)



	n	Min.	Max.	HAFT 2	Median	Mean	Std. Dev.

Nicosulfuron

Grass forage	1 application;

0.056-0.061	0	24	0.032	5.7	5.0	3.7	3.5	1.3

Grass hay

0 [2-8]	24	0.11	10	9.3	6.2	5.5	3.2

Grass forage

(2nd cutting)	2 applications;

0.085-0.091	0	24	0.53	3.6	3.6	1.9	1.8	0.1

Grass hay

(2nd cutting)

0 [2-7]	24	1.6	7.3	5.9	3.0	3.4	1.5

Grass forage	1 application;

0.088-0.092	0	24	3.4	8.2	7.7	5.4	5.6	1.1

Grass hay

0 [2-8]	24	0.26	18	18	12	10	4.3

IN-V9367

Grass forage	1 application;

0.056-0.061	0	24	<0.010	0.28	0.26	0.16	0.16	0.07

Grass hay

0 [2-8]	24	<0.010	0.93	0.87	0.43	0.40	0.27

Grass forage

(2nd cutting)	2 applications;

0.085-0.091	0	24	0.024	0.26	0.19	0.092	0.10	0.05

Grass hay

(2nd cutting)

0 [2-7]	24	0.084	0.47	0.43	0.24	0.24	0.10

Grass forage	1 application;

0.088-0.092	0	24	0.15	0.59	0.57	0.23	0.27	0.11

Grass hay

0 [2-8]	24	0.016	1.2	1.2	0.59	0.63	0.34

1. For hay, days dried in the field are reported in brackets.  

2. HAFT = Highest Average Field Trial.  

	Residues in grass forage and hay were comparable regardless of whether
an NIS, COC, ammonium sulfate, or urea/ammonium nitrate fertilizer was
used as the spray adjuvant.  Maximum residues of nicosulfuron were
observed in samples of Treatment 1a grass forage and Treatment 1b grass
forage and hay following application with fertilizer as an adjuvant. 
However, maximum residues of IN-V9367 were observed only in samples
following application with an NIS or COC as a spray adjuvant.  Likewise,
spray volumes did not appear to have a significant impact on residues of
nicosulfuron nor IN-V9367 in forage and hay.  

	It was noted that the petitioner provided data indicating that hay
samples from most trial sites were dried to a moisture content of
11.2-39.0%; samples from one trial site (Trial 09; Treatments 1a and 2)
had a moisture content of 61.3-61.6%.  Table 1 of OPPTS Residue
Chemistry Test Guideline 860.1000 recommends a moisture content of
10-20% for hay.  

	The study did not investigate residue decline.  

	Conclusions:  The submitted residue data for grass forage and hay are
acceptable.  The number and location of field trials are in accordance
with OPPTS Guideline 860.1500 for grasses.  The study reflects the
maximum proposed use pattern on grasses, and samples were analyzed for
nicosulfuron, the ROC, as well as its metabolite, IN-V9367, using an
acceptable method.  However, additional storage stability and residue
decline data are required to support the study.  Per OPPTS Guideline
860.1500, residue decline data are required when a pesticide is applied
when the edible portion of the crop has formed, and it is clear that
residues may occur on the food or feed commodities at, or close to, the
earliest harvest time.  

	Pending submission of outstanding concurrent storage stability data
(see section 860.1380), and a single residue decline trial conducted
according to the maximum proposed use pattern, the available field trial
data support tolerances for residues of nicosulfuron in grass forage at
9.0 ppm, and in grass hay at 25 ppm.  

	It was noted that the submitted data are sufficient with respect to the
number of field trials, varieties used, and residues found by variety to
support crop group tolerances in group 17, grass forage, fodder, and
hay.  

860.1520 Processed Food and Feed

	HED does not require residue data for any processed commodities
associated with grasses.  Therefore, data requirements for processed
food and feed are not relevant to this tolerance petition.  

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

	An analytical standard for nicosulfuron is currently in the EPA
National Pesticide Standards Repository, per communication with Dallas
Wright, of the Biological and Economic Analysis Division’s (BEAD’s)
Analytical Chemistry Branch (ACB), on 1 June 2009.  However, the
standard expired on 14 October 2009.  The registrant should either
recertify the lot in the repository, and send in an updated certificate
of analysis (COA), or submit a new standard (having a different lot
number) if the previous lot will not be recertified.  If a new COA is
being submitted, it should be faxed to the repository at (410)305-2999. 


	If a new standard is being submitted, it should be sent to the
Analytical Chemistry Lab (located at Fort Meade), to the attention of
Theresa Cole, at the following address:

	USEPA

	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

	701 Mapes Road

	Fort George G. Meade, MD  20755-5350

(Please note that the mail will be returned if the extended zip code is
not used.)  

860.1850 Confined Accumulation in Rotational Crops

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	An acceptable confined rotational crop study was previously submitted,
reflecting application of [pyridine-2-14C]-nicosulfuron or
[pyrimidine-2-14C]-nicosulfuron to the soil at 0.062 lb ai/A (70 g
ai/ha, roughly 0.7X the maximum proposed seasonal application rate on
Bermuda grass).  The study was reviewed by the Environmental Fate and
Effects Division (EFED) in E. Regelman’s memo of 1 June 1990. 
Rotational crops were planted 1, 4 and/or 10 months after application as
follows:  

1. Soybeans at 30 and 120 days, and 10 months.  

2. Lettuce and wheat at 120 days, and 10 months.  

3. And, radishes at 10 months.  

All crops were harvested at maturity.  

	The data indicated that metabolites and/or degradates containing the
pyridine ring are more readily taken up by plants than those containing
the pyrimidine ring.  Residues of the pyrimidine amine (IN-J290) were
not detected in soils or plants, even though this metabolite is a major
metabolite/degradate of nicosulfuron.  With the pyrimidine-labeled
material, total residues were lower, and the only identified
metabolite/degradate was N-desmethyl nicosulfuron, which was higher in
forage and hay than in seeds.  Maximum total residues were observed in
soybean forage, hay and seed when the pyridine-labeled material was
used, but the amount of residues decreased with the aging period of the
soil.  The major metabolite detected was pyridine sulfonamide
(IN-V9367).  Maximum total residues were also observed in wheat straw
and chaff when the pyridine-labeled nicosulfuron was used; pyridine
sulfonamide (IN-V9367) was the major metabolite/degradate identified. 
The lowest residues were identified in lettuce leaves, and radish roots.
 

	Based on the results of the confined rotational crop study, it was
concluded that nicosulfuron is hydrolyzed rapidly in acidic soils, with
the formation of pyridine sulfonamide, and pyrimidine amine as the
metabolites, which are then taken up by the plant.  A 10-month PBI was
recommended, based on phytotoxic effects.  HED concluded that the ROC in
rotated crops is the parent compound, nicosulfuron.  

860.1900 Field Accumulation in Rotational Crops

	HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004)

	Residue Chemistry Memo D208793; G. Kramer; 16 June 1995

	Three limited field trials on soybeans were conducted in IL, DE and MS
in 1991.  The 75% WDG formulation of nicosulfuron was applied, at the
rate of 0.063 lb ai/A, to corn at the 10-leaf stage.  The application
rate corresponds to 0.7X the maximum proposed seasonal application rate
to grasses (1X the maximum registered rate for corn).  The corn was cut,
and soybeans were planted 7, 15 and 30 days after treatment (DAT). 
Soybean forage and hay were harvested 39-73 DAT; soybean grain and
straw, at 116-160 DAT.  No measurable residues (<0.05 ppm) of
nicosulfuron were found in any soybean sample.  No residues of the major
metabolite, IN-V9367, were measured (<0.05) in grain.  

	Based on the submitted studies, the Agency concluded that the study
results would support a minimum PBI of 7 days for soybeans.  EFED also
approved reduction of the PBI for wheat from 10 months to 4 months.  

	Conclusions:  The maximum proposed application rate of 0.088 lb ai/A on
grasses exceeds the maximum rate used in the confined rotational crop
study, and the field rotational crop study on soybeans of 0.063 lb ai/A.
 

	Although the petitioner has proposed rotational crop restrictions that
are based on a maximum application rate (0.070 lb ai/A) that is
consistent with the maximum registered use on corn (0.063 lb ai/A), RAB2
does not believe these restrictions are practical.  In consideration of
the expanded use of nicosulfuron on grasses, RAB2 now requires
submission of a limited rotational crop study to determine whether
residues of nicosulfuron will occur in rotational crops under actual
field conditions, and to establish appropriate rotational crop
restrictions based on the maximum use pattern.  The limited rotational
crop trials should be conducted, as specified under OPPTS Residue
Chemistry Test Guideline 860.1900, on representative crops of root and
tuber vegetables, leafy vegetables or soybeans, and small grains, and
should reflect an application rate of 0.088 lb ai/A.  

860.1550 Proposed Tolerances

	Tolerances for nicosulfuron in plant commodities are currently
established under 40CFR §180.454, and are expressed in terms of the
parent compound, nicosulfuron.  HED has determined that the ROC in plant
and livestock commodities is nicosulfuron only.  The tolerance
expression proposed by DuPont is consistent with HED’s conclusions;
however it was noted that the regulatory citation is 40CFR §180.478[a],
which corresponds to rimsulfuron.  Additionally, according to HED’s
Interim Guidance on Tolerance Expressions (S. Knizner, 27 May 2009), the
tolerance expression for nicosulfuron cited in 40CFR §180.454 should be
revised to state:  

Tolerances are established for residues of nicosulfuron, including its
metabolites and degradates, in or on the commodities listed in the table
below.  Compliance with the tolerance levels specified below is to be
determined by measuring only nicosulfuron
(2-[[[[(4,6-dimethoxy-2-pyrimidinyl) amino] carbonyl] amino]
sulfonyl]-N,N-dimethyl-3-pyridinecarboxamide).  

	The tolerances proposed by DuPont are listed in Table 7 (below), along
with the tolerance levels recommended by RAB2.  The proposed tolerances
in grass and ruminant commodities, listed in Section F, should be
revised to reflect the recommended tolerances specified in Table 7.

	Adequate data, reflecting the proposed use pattern, are available for
purposes of establishing tolerances in grass forage and hay.  The
tolerance spreadsheet in the Agency’s Guidance for Setting Pesticide
Tolerances Based on Field Trial Data was utilized for determining
appropriate tolerance levels (refer to Appendix II).  The data indicate
that the proposed tolerances of 9.0 ppm in grass forage, and 25 ppm in
grass hay are appropriate.  

	An acceptable cattle feeding study has been submitted in support of the
proposed use on grasses.  The data indicate that tolerances are needed
in milk, and in the liver, kidney, muscle and fat of cattle, goat, horse
and sheep.  Tolerances are not needed in milk fat, nor in swine
commodities.  Tolerances in milk, meat, and fat should be set at 0.01
ppm (the LOQ), and in meat byproducts at 0.05 ppm.  

	No Codex or Mexican MRLs are established for residues of nicosulfuron;
Canadian MRLs are established in blueberries and corn, and are expressed
in terms of nicosulfuron.  Harmonization of tolerances is not an issue
for this tolerance petition.  

Table 7	Tolerance Summary for Nicosulfuron.  

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;
Correct Commodity Definition

Grass, forage	9.0	9.0

	Grass, hay	25.0	25

	Cattle, fat	0.05	0.01

	Cattle, meat byproducts	0.05	0.05

	Cattle, meat	0.05	0.01

	Goat, fat	0.05	0.01

	Goat, meat byproducts	0.05	0.05

	Goat, meat	0.05	0.01

	Hog, fat	0.05	Not needed.  	Tolerances are not needed in hog
commodities because there are no swine feed items associated with the
proposed use on grasses, and the dietary burden to swine (resulting from
use on corn) is low enough that there is no reasonable expectation of
finite residues in hog commodities (40CFR §180.6[a][3]).  

Hog, meat byproducts	0.05



Hog, meat	0.05



Horse, fat	0.05	0.01

	Horse, meat byproducts	0.05	0.05

	Horse, meat	0.05	0.01

	Milk	0.05	0.01

	Milk, fat	0.02	Not needed.  	A tolerance is not needed because residues
do not concentrate in cream.

Sheep, fat	0.05	0.01

	Sheep, meat byproducts	0.05	0.05

	Sheep, meat	0.05	0.01

	



References

	Nicosulfuron.  Human Health Risk Assessment for the Proposed Use on
Grasses.; D360807; M.A. Doherty; 27 October 2009.  

	  SEQ CHAPTER \h \r 1 PP#9F3763.  DPX-V9360 in/on corn grain, forage,
fodder, and silage.  Results of Petition Method Validation and Comments
on Independent Laboratory Validation of DPX-V9360 Methodology for Corn
Fodder.; DEB Numbers 5234-5326 and 6501-6503; J. Stokes; 4 May 1990.  

	  SEQ CHAPTER \h \r 1 ID# 00352-00560.  Review of label amendment for
nicosulfuron (Accent SP Herbicide) to reduce plantback interval for
soybeans.  Case 026774.  CBTS# 14652.; D208793; G. Kramer; 16 June 1995.
 

	  SEQ CHAPTER \h \r 1 Nicosulfuron HED Chapter of the Reregistration
Eligibility Decision Document (RED).  PC Code:  129008, Case #:  none.;
D302694; D. Hrdy, A. Khasawinah, J. Stokes, M. Crowley, and J. Miller,
and L. Liu; 30 November 2004.  

	  SEQ CHAPTER \h \r 1 Nicosulfuron:  Section 3 Registration of
Nicosulfuron 2L (EPA File Symbol:  67760-TU) for Use on Corn.  Summary
of Analytical Chemistry and Side-by-Side Residue Data.; D338945 and
D342602; 	A. Parmar; 18 October 2007.  

  SEQ CHAPTER \h \r 1 Attachments

International Residue Limit Status Sheet

Appendix I - Chemical Name and Structure Table

Appendix II - Tolerance Assessment Calculations



INTERNATIONAL RESIDUE LIMIT STATUS

CAS Name:  2-[[[[(4,6-dimethoxy-2-pyrimidinyl) amino] carbonyl] amino]
sulfonyl]-N,N-dimethyl-3-pyridinecarboxamide	Common Name:

Nicosulfuron	X Recommended tolerances

⁮ Re-evaluated tolerance

	

 

 

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1 June 2009

Codex Status (Maximum Residue Limits)	US Tolerances

X No Codex proposal step 6 or above

⁮ No Codex proposal step 6 or above for the crops requested	Petition
Number:  8F7501

DP Barcode:  D360897 (Decision #404568)

Other Identifier:  PC Code 129008

Residue definition (step 8/CXL):  NA	Reviewer/Branch:  William T.
Drew/RAB2

	Residue definition:  Nicosulfuron

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



Grass, forage	9.0



Grass, hay	25



Cattle, fat	0.01



Cattle, meat byproducts	0.05



Cattle, meat	0.01



Goat, fat	0.01



Goat, meat byproducts	0.05



Goat, meat	0.01



Horse, fat	0.01



Horse, meat byproducts	0.05



Horse, meat	0.01



Milk	0.01



Sheep, fat	0.01



Sheep, meat byproducts	0.05



Sheep, meat	0.01

Limits for Canada	Limits for Mexico

⁮ No Limits

X No Limits for the crops requested	X No Limits

⁮ No Limits for the crops requested

Residue definition:  2[[[[(4,6-dimethoxy-2-pyrimidinyl) amino] carbonyl]
amino] sulfonyl]-N,N -dimethyl-3-pyridinecarboxamide	Residue definition:
 NA

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

























	Notes/Special Instructions:  Steve Funk, 21 June 2009.  NA = Not
Applicable.  



Appendix I - Chemical Name and Structure Table

APPENDIX I	Chemical Names and Structures of Nicosulfuron and
Metabolites.  

Company Code; 



* Tentative structure was determined by the study reviewer, as the
original review was unavailable.  

Appendix II - Tolerance Assessment Calculations

	The dataset used to establish tolerances for nicosulfuron in grass
forage and hay consisted of field trial data representing an application
rate of 0.088 lb ai/A, from a single application, with a 0-day PHI.  As
specified by the Guidance for Setting Pesticide Tolerances Based on
Field Trial Data (SOP), the field trial application rates and PHIs are
within 25% of the maximum label application rate, and minimum label PHI,
respectively.  The residue values that were entered into the tolerance
spreadsheet are provided in Table II-1 (below).  The results from the
grass field trials in which a single application was made at
approximately 0.088 lb ai/A were used for the tolerance calculations.  

	All field trial sample results for grass forage and hay were above the
LOQ (LOQ = 0.010 ppm).  For grass forage, visual inspection of the
lognormal probability plot (Figure II-1, below), and the results from
the approximate Shapiro-Francia test statistic (Figure II-2, below)
indicated that the dataset was reasonably lognormal.  For grass hay,
visual inspection of the lognormal probability plot (Figure II-3,
below), and the result from the approximate Shapiro-Francia test
statistic (Figure II-4, below) indicated that the assumption of
lognormality should be rejected.  

	Since the field trial data for nicosulfuron on grass forage represent a
large dataset (24 samples), and are reasonably lognormal, the minimum of
the 95% upper confidence limit (UCL) on the 95th percentile, and the
point estimate of the 99th percentile, should be selected as the
tolerance value.  Using the rounding procedure as outlined in the SOP,
both the 95% UCL on the 95th percentile, and the point estimate of the
99th percentile, round to the value 9.0 ppm (Figure II-2).  Therefore,
9.0 ppm is the recommended tolerance level for nicosulfuron in grass
forage.  

	Since the field trial data for nicosulfuron on grass hay are not
lognormal, the upper bound on the 89th percentile should be selected as
the tolerance value (distribution-free method).  Using the rounding
procedure as outlined in the SOP, the upper bound on the 89th percentile
rounds to the value 25 ppm.  Therefore, 25 ppm is the recommended
tolerance level for nicosulfuron in grass hay.  



Table II-1	Residue Data Used to Calculate ToleranceS for Nicosulfuron in
Grass Forage and Hay.  

Regulator:	EPA	EPA

Chemical:	Nicosulfuron	Nicosulfuron

Crop:	Grass forage	Grass hay

PHI:	0 Days	0 Days

App. Rate:	0.88 lb ai/A	0.88 lb ai/A

Submitter:	E.I. DuPont de Nemours and Company	E.I. DuPont de Nemours and
Company

MRID Citation:	MRID #47632204	MRID #47632204

	Residues of Nicosulfuron (ppm)

	4.7	12

	5.2	12

	6.3	13

	6.3	15

	4.6	11

	5.3	12

	7.1	13

	8.2	12

	7.3	8.3

	6.1	10

	3.9	8.6

	4.9	7.1

	5.6	18

	4.9	17

	4.7	6

	3.4	6.3

	5.5	0.3

	6.8	0.26

	6.2	12

	4.9	12

	4.5	11

	4.9	10

	5.9	14

	6.6	8.7





Figure II-1	Lognormal Probability Plot of Nicosulfuron Field Trial Data
(Grass Forage).  



Figure II-2	Tolerance Spreadsheet Summary of Nicosulfuron Field Trial
Data (Grass 			Forage).  



 h$ 

 h$ 

 h$ 

hB

kd

kdÅ

kdm

 hB

hB

  hB

hB

hB

  hB

 hB

kd

摧䊭

robability Plot of Nicosulfuron Field Trial Data (Grass Hay).



Figure II-4	Tolerance Spreadsheet Summary of Nicosulfuron Field Trial
Data (Grass 			Hay).

Nicosulfuron	Summary of Analytical Chemistry and Residue Data	DP
Barcode:  D360897

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