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

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

OFFICE OF PREVENTION,

PESTICIDES AND TOXIC SUBSTANCES

MEMORANDUM

DATE: 6 November 2009

SUBJECT: Nicosulfuron: Petition 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.

PC Code: 129008 DP Barcode: D360897

Decision Number: 404568 Registration Number: 352-IRO (File Symbol)

Petition Number: 8F7501 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case Number: NA

TXR Number: NA CAS Number: 111991-09-4

MRID Numbers: 47632204, 47632206 to 

-212, 47640501

40CFR: §180.454

Chemical Class: Pyrimidinylsulfonylurea Trade Name: DuPont PastoraTM

FROM: William T. Drew, Chemist

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

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. 
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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 (PastoraTM 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 
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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 (DuPont17927). 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 
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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. 

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 
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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. 
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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-dimethyl-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. 
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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. 
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TABLE 1 Nicosulfuron Nomenclature. 

Chemical structure

N

O

N

H3C CH3

S

NH NH

N

N O

O

CH3

CH3

O O

O

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-dimethylnicotinamide;

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-dimethyl3-pyridinecarboxamide

CAS registry number 111991-09-4

End-use product (EP) 56.2% DF formulation (PastoraTM 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/cm3relative 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
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TABLE 2 Physicochemical Properties of Nicosulfuron. 

Parameter Value Reference

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 

(PastoraTM 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;

broadcast; ground 

(≥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;

broadcast; 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. 
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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. 

Additional rotational crop restrictions are specified for crop areas with soil pH ≤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 
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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 
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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 [pyrimidine2-

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 pyridinelabel 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. 

Extraction with acetone/0.1M ammonium carbonate released the majority of radioactivity

(87-99% TRR) from immature foliage for both labels and rates. For mature matrices (at both 

treatment rates for foliage and pods, and at the exaggerated rate only for seeds), extraction with 
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acetone/0.1M ammonium carbonate released 58-65% TRR (pyridine label) and 47-50% TRR 

(pyrimidine label) from foliage, 57-77% TRR (pyridine label) and 39-63% TRR (pyrimidine 

label) from pods, and 61-66% TRR (both labels) from seeds. Extraction procedures were slightly

more successful for pyridine-label matrices than for pyrimidine-label matrices, except with seeds. 

Non-extractable residues accounted 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%. 

The metabolite profiles were similar for both treatment levels. Nicosulfuron was the 

major residue identified in immature canola foliage from all harvest intervals for both labels. 

Residues generally decreased with increasing harvest intervals, from 78-90% TRR in 0-day

foliage, to 52-80% TRR in 10-day foliage, and 36-81% TRR in 30-day foliage. Nicosulfuron 

was a secondary residue in mature matrices for both labels, accounting for 5-11% TRR in 

foliage, 17-31% TRR in pods, and 7-10% TRR in seeds. The pyridine-ring metabolite INV9367, and the pyrimidine-ring metabolites IN-H1043 or IN-J290 were the major identified 

residues in mature foliage, pods and seeds from the respective labels. IN-V9367 accounted for 

24-28%, 23-24%, and 18% TRR in pyridine-label mature foliage, pods and seeds, respectively, 

but was present at lower levels in immature foliage (3-28% TRR). Metabolite IN-H1043 

accounted for 15-16% and 4-7% TRR in pyrimidine-label mature foliage and pods, respectively, 

but was not identified in seeds, and was present at lower levels in immature foliage (2-11% 

TRR). Metabolite IN-J290 was the major identified residue in pyrimidine-label seeds at 23% 

TRR, but was present at lower levels in mature foliage and pods (1-3% TRR), and immature 

foliage (1-15% TRR). No other metabolite was identified in seeds. Hydroxylated nicosulfuron, 

Metabolite 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 
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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 INV9367 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 IN70940 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 shortlived, generally decreasing to <0.010 ppm within 14 days of 

application, and were generally more polar than the parent. 

4. Formation of new metabolites given the proposed 0-day PHI for 

grass would be unlikely, and if new metabolites were 

generated, their concentration would be expected to be 

small. 

5. Under the intended use pattern on grasses, forage could be 

grazed from 0-30 days after application, and concentrations 

of metabolites, including IN-V9367 were roughly ≤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. 
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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. 

The maximum TRR in milk (pyrimidine label only) were 0.03 ppm. In tissues, liver had 

the highest TRR (0.1 ppm; pyrimidine label), while TRR in other tissues were ≤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. 
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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, DuPont17928, 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%,
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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 INV9367. 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 
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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, INV9367, 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 INV9367. 

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 
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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. 
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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. 
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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
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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

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 
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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. 

In tissues, the highest residues were observed in kidney, followed by liver and muscle, 

with the lowest residues observed in fat; residues in tissues were dose-dependent. Detectable 

residues of nicosulfuron and IN-V9367 were observed in tissue at all feeding levels, except in 

muscle (IN-V9367) and fat (both analytes) at the 20-ppm feeding level. Residues of nicosulfuron 

in liver were <0.010-0.016, 0.020-0.033, 0.053-0.073, and 0.21-0.34 ppm, at the 20-, 50-, 150-

and 500-ppm feeding levels, respectively; corresponding residues of IN-V9367 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 
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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 
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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 INV9367 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. 
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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. HAFT2 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 
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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.

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 
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(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. 
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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 
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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
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References

Nicosulfuron. Human Health Risk Assessment for the Proposed Use on Grasses.; 

D360807; M.A. Doherty; 27 October 2009. 

PP#9F3763. DPX-V9360 in/on corn grain, forage, fodder, and silage. Results of 

Petition Method Validation and Comments on Independent Laboratory Validation of DPXV9360 Methodology for Corn Fodder.; DEB Numbers 5234-5326 and 6501-6503; J. Stokes; 4

May 1990. 

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. 

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. 

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. 

Attachments

International Residue Limit Status Sheet

Appendix I - Chemical Name and Structure Table

Appendix II - Tolerance Assessment Calculations
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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

⁮ Other

Date: 21 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. 
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Appendix I - Chemical Name and Structure Table

APPENDIX I Chemical Names and Structures of Nicosulfuron and Metabolites. 

Company Code; 

Common Name

Chemical Name Chemical Structure

Nicosulfuron 2-[[[[(4,6-dimethoxy-pyrimidin-2-

yl)-amino]carbonyl]amino]sulfonyl]-

N,N-dimethyl-3-

pyridinecarboxamide

N

O

N

H3C CH3

S

NH NH

N

N O

O

CH3

CH3

O O

O

IN-V9367; pyridine 

sulfonamide

[2-aminosulfonyl]-N,N-dimethyl-3-

pyridinecarboxamide

N

O

N

H3C CH3

S

NH2

O

O

IN-70940 and its glucose 

conjugate

2-[[[[(4,6-dimethoxy-5-hydroxypyrimidin-2-

yl)amino]carbonyl]amino]-sulfonyl]-

N,N-dimethyl-3-

pyridinecarboxamide

N

O

N

H3C CH3

S

NH NH

N

N O

O

CH3

CH3

O O

O

OH

IN-J290; pyrimidine amine 2-amino-4,6-dimethoxy-pyrimidine

N

N O

O

CH3

CH3

H2N

IN-H1043 2-amino-4,6-dihydroxypyrimidine

N

N OH

OH

H2N
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APPENDIX I Chemical Names and Structures of Nicosulfuron and Metabolites. 

Company Code; 

Common Name

Chemical Name Chemical Structure

N-desmethyl nicosulfuron*

N

O

HN

CH3

S

NH NH

N

N O

O

CH3

CH3

O O

O

* Tentative structure was determined by the study reviewer, as the original review was unavailable. 
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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. 
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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
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Figure II-1 Lognormal Probability Plot of Nicosulfuron Field Trial Data (Grass Forage). 

Lognormal Probability Plot

0.1 1 2 5 10 20 30 50 70 80 90 95 98 99 99.9

9.0000

4.5000

2.2500

y = 0.2108x + 1.6982

R

2

 = 0.979

Percentiles

Concentrations

EPA Nicosulfuron Grass forage 0 Days 0.088 lb ai/A E.I. DuPont de Nemours and Company
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Figure II-2 Tolerance Spreadsheet Summary of Nicosulfuron Field Trial Data (Grass 

Forage). 

Regulator: EPA

Chemical: Nicosulfuron

Crop: Grass forage

PHI: 0 Days

App. Rate: 0.088 lb ai/A

Submitter: E.I. DuPont de Nemours and Company

n: 24

min: 3.40

max: 8.20

median: 5.40

average: 5.58

95th Percentile 99th Percentile 99.9th Percentile

8.0 9.0 10

(9.0) (10) (--)

8.0 9.0 11

(9.0) (11) (--)

13

9.0

30

0.9790

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
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Figure II-3 Lognormal Probability Plot of Nicosulfuron Field Trial Data (Grass Hay).

Lognormal Probability Plot

0.1 1 2 5 10 20 30 50 70 80 90 95 98 99 99.9

18.0000

9.0000

4.5000

2.2500

1.1250

0.5625

0.2813

0.1406

y = 0.8172x + 2.0827

R

2

 = 0.5454

Percentiles

Concentrations

EPA Nicosulfuron Grass hay 0 Days 0.088 lb ai/A E.I. DuPont de Nemours and Company
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Figure II-4 Tolerance Spreadsheet Summary of Nicosulfuron Field Trial Data (Grass 

Hay).

Regulator: EPA

Chemical: Nicosulfuron

Crop: Grass hay

PHI: 0 Days

App. Rate: 0.088 lb ai/A

Submitter: E.I. DuPont de Nemours and Company

n: 24

min: 0.26

max: 18.00

median: 11.50

average: 10.40

95th Percentile 99th Percentile 99.9th Percentile

18 25 25

(25) (25) (--)

50 100 220

(100) (250) (--)

30

25

65

0.5454

p-value <= 0.01: Reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD