Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 1 of 40 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM DATE : 6 November 2009 SUBJECT: Nicosulfuron: Petition Requesting Establ ish ment 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: D 3608 9 7 Decision Number : 404568 Registration Number : 352 - IR O (File Sy mbol) Petition Number : 8 F 7501 Regulatory Action: Section 3 Registration Risk Assessment Type: NA Case Number : NA T XR Number : NA CAS Number : 111991 - 09 - 4 MRID Numbers : 47632204, 47632206 to

- 212, 47640 501 40CFR : § 180. 454 Chemical Class: P yrimidinyl sulfonylurea Trade Name: DuPont PastoraTM FROM: William T. Drew, Chemist

Ris k A ssessment Branch 2 (RAB2) Health Effects Division (HED), 7509P THRU: Douglas Dotson , Chemist

RAB2/HED, 7509P TO: Mindy

Ondish and J am es Tompkins , RM Team 25 Herbicide Branch ( HB) Registration Division ( RD), 7505 P 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 He alth Effects Division (HED), and revised to reflect current Office of Pesticide Programs (OPP) policies.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 2 of 40 Executive Summary Nicosulfuron , with CAS name 2 - [[[[(4,6 - dimethoxy- 2 - py rimidinyl) amino] carbonyl] amino] sulfonyl] -N,N

- dimethyl - 3 - py

ridinecarbox amide , is a member of the py rimidinyl sulfonylurea family of herbicides . It is currently registered to DuPont Crop Protection for use on corn, at a maximum seasonal rate of 0.06 3 pounds of active ingredient per acre ( lb ai/A ) ; DuPont has previously indicat ed that they intend ed to propose a new use on sorghum . A Tolerance Reassessment Progress and Risk Management Decision (TRED) was issued for nicosulfuron in December 2 0 04, and the HED Chapter of the Reregistration Eligibility Decision ( RED ) was issued on 3 0 November 20 04 (D 302694; D. Hrdy ). DuPont has submitted a petition ( PP#8 F 7501) 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 by

products .......................................... 0.05 ppm Cattle, meat ....................................................... 0.05 ppm Goat, fat ............................................................ 0.05 ppm Goat, meat by

products ...... ..................................... 0.05 ppm Goat, meat ......................................................... 0.05 ppm Hog, fat ............................................................ 0.05 ppm Hog, meat by

products ............................................ 0.05 ppm Hog, meat ......................................................... 0.05 ppm Horse, fat .......................................................... 0.05 ppm Horse, meat by

products .................. ........................ 0.05 ppm Horse, meat ........................................................ 0.05 ppm Milk ................................................................ 0.05 ppm Milk, fat ............................................................ 0.02 ppm Sheep, fat .......................................................... 0.05 ppm Sheep, meat by

products .......................................... 0.05 ppm Sheep, meat ...................................................... . 0.05 ppm Inconjunction 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 Sy mbol 352 - IR O ). This product is a multiple active ingre dient (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 maxi mum 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 specifi ed. The subject review only addresses the adequacy

of the available data to supportNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 3 of 40 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 f

ield and sweet corn commodities. No tolerances in livestock commodities have been established. The nature of the residue in plants is adequat ely 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 enf

orcement , 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 dete ction ( HP LC /MS/MS) methods for the determination of residues of nicosulfuron in grass forage and hay (DuPont - 17928) , and livestock commodities (DuPont 17927). Both methods determine residues of metabolite I N - V9367 separately . The method limit of quantitation (L OQ) is 0.010 ppm for each analy te 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 , a s 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 egg s should be submitted. In addition, the peti tioner 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 studi es. Multiresidue methods testing data were previously submitted for nicosulfuron , which indicat ed that the methods are not applicable to nicosulfuron determination. A livestock feeding study was submitted , reflecting dosing of lactating dairy cows wi th nicosulfuron at target dose rates of 20, 50, 15 0 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 I N - 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 L OQ of 0.01 ppm , and in meat by products at 0.05 ppm. A tolerance is not needed in milk fat because residues did not concentrate in cream. Tolerances areNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 4 of 40 not needed in hog commodities because there are no swine feed items associated with the proposed use on grasses, and the dietary burden t o swine (resulting from use on corn) is low e nough that there is no reasonable expectation of finite residues in hog commoditie s (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 request ed 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. Itwas 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 phy totoxic effects, and the PBI for soy bean s was refined , based on a limited field rotational crop study on soy bean s only , reflecting application at 0.0 63 lb ai/A. The petitioner has proposed rotation al 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) , an d 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 o rder 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 condu cted , as specified under OPPTS Residue Chemistry Test Guideline 860.1900 , on representative crops of root and tuber vegetables, leafy vegetables or soy bean, and small grains, and should reflect an application rate of 0.088 lb ai/A. No Codex or Mexican M aximum Residue L imits ( MRL s ) have been established; Canadian MRL s are established in blueberries and corn , and are expressed in terms of nicosulfuron. Regulatory Recommendations and Residue Chemistry Deficiencies RAB2 has examin ed 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 Analy tical Methods), a revised Section F (see requirements under Proposed Tolerances), and an analy tical reference standard for nicosulfuron (see requirements under Submittal of Analy tical Reference Standards), there are no residue chemistry

issues that would preclude granting conditional registration for the requested use of nicosulfuron on grasses , n or the establishment of permanent tolerances for residues ofNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 5 of 40 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 . Comp liance with the tolerance le vels 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 by

products ................................ ...................... 0.05 ppm Cattle, meat ................................ ................................ ........ 0.01 ppm Goat, fat ................................ ................................ .............. 0.01 ppm Goat, meat by

products ................................ ....................... 0.05 ppm Goat, meat ................................ ................................ .......... 0.0 1 ppm Horse, fat ................................ ................................ ............ 0.01 ppm Horse, meat by

products ................................ ...................... 0.05 ppm Horse, meat ................................ ................................ ........ 0.01 ppm Milk ................................ ................................ .................... 0.01 ppm Sheep, fat ................................ ................................ ............ 0.01 ppm Sheep, meat by

products ................................ ..................... 0.05 ppm Sheep, meat ................................ ................................ ........ 0.01 ppm A list of deficiencies, as noted elsewhere in this document, is presented below. 86 0.1200 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 ref lect the maximum proposed seasonal use rate on grass es of 0.088 lb ai/A. 860.1340 Residue Analytical Methods Plant C ommodities  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.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 6 of 40 Livestock C ommodities  For method DuPont - 17927 to be suitable for enforcement purposes, supporting raw data fo r method validation in egg s 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 sec tion referenced there in reflect s the c orrect section for nicosulfuron, §180.454.  T he proposed tolerances in milk, and in the meat and fat of ruminants , should be re duc ed 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 by products 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 20 09), the tolerance e xpression for nicosulfuron c ited in 40CFR §180.454 should be revised to state:

Tolerances are established for residues of nicosulfuron, including i t s metabolites and degradates, in or on the commodities listed in the table below. Compliance with the to lerance 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 reg istration for the requested us e on grasses be converted to unconditional registration upon submission of the residue chemistry data listed below. 860.1380 Storage Stability Grass Forage and H ay  The petitioner should submit the final concurrent storage stability report , reflecting storage stability

of nicosulfuron and I

N - V9367 in grass forage and hay stored frozen for intervals of up to 9.6 and 12.4 months, respectively . Livestock T issues  The petitioner should submit the outstanding storage stability study , reflecting storage s tability of nicosulfuron and I

N - V9367 in livestock tissues stored frozen for intervals of up to 9.4 months.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 7 of 40 860.1500 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

 Inconsideration of the expanded use of nicosulfuron on grasses, RAB2 now requires submission of a limited rotational crop study , in order to determine whether residue s 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 soy

bean, and small grains, and should reflect an application rate of 0.088 lb ai/A. Background Nicosulfuron is a member of the py rimidi nyl sulfonylurea 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, p igwee d 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 enzy

me acetolactate sy

nthase (ALS), leading to the disruption of cell div ision 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 prod ucts are presented in Appendix I .Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 8 of 40 TABLE 1 Nicosulfuron Nom enclatur e. Chemical structure

N O N C H 3 C H 3

S N H NH N N O

O C H 3 C H 3 O O O

Common name Nicosulfuron Company experimental name DPX - V9360 Molecular formula C 15 H 18N 6 O 6 S Molecular weight 41 0.40 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 - dimethyl 3 - 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 .

Param eter Value Reference Melting point/range 18 3.3 ± 0.3 °C MRID #4 7632204 pH 4.5 MRID #4 7632204 Density 1.441 ± 0.006 g/cm3 relative density MRID #4 7632204 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 M RID #4 7632204 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 #4 7632204Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 9 of 40 TABLE 2 Physicochemical Properties of Nicosulfuron .

Param eter Value Reference Vapor pressure ( at 25°C) 1.2 x 10 - 16 Torr MRID #4 7632204 Dissociation constant, pKa 4.22 MRID #4 7632204 Octanol/water partition coefficient, KOW ( at 25°C ) pH 5 = 0.44 pH 7 = 0.02 pH 9 = 0.007 MRID #4 76322 04 UV/visible absorption spectrum ( at 20°C ) No absorbance maxima at or above 290 nm for acidic, basic or neutral solutions . MRID #4 7632204 860.1200 Directions for Use DuPont has submitted a draft label (dated December 2 0 08) for the 56.2% DF formulat ion (PastoraTM Herbicide; EPA File Sy mbol 352 - IR O ). The product is an MAIformulation 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. Applic ation Timing; Type ; Equipment Form ulation

[EPA File Symbol ] Use Rate

(lb ai/A) Max.

Uses per Season Max.

Seasonal Use Rate (lb ai/A) PHI

( D ays) Use Directions and

Limitations 1 Berm uda G rass Pastures and H ay M eadows 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 diame ter. Use o f 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 G rown 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 = N on - I onic S urfactant . COC = C rop O il C oncentrate. 2. GPA = Gallons Per Acre. 3. The label states that there are no grazing or haying restrictions.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 10 of 40 Application through any

ty pe of irrigation system , or to grasses grown for seed is p rohibited. No RTI s 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 PBIfor wheat (except durum), Ber muda grass, blue grass, ryegrass and tall fescue following application of the 56.2% DF for

mulation at up to 0.070 lb ai/A. 2. A 10 - mo nth PBIfor durum wheat, barley and oats following app lication at up to 0.053 lb ai/A. 3. And, a 12 - month PBIfor alfalfa , and red, whit e 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) soy beans . 2. And, a 12 - month PBIfor 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 mixe d 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, d icamba, triclopy r, 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 season al 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 ty

pical grass forage and hay stage s to support the proposed use. No RTI s were specified. The submitted field trial data support a minimum RTIof 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 PBI s, 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 onNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 11 of 40 grass (refer to section 860.1900). When these data have been submitted , the petitioner sho uld revise the rotational crop restrictions to reflect the maximum proposed seasonal rate on grass es 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 C anola) MRID # 47632212 ( Justification to Cite Existing D ata , R eviewed H erein) HE D 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 C hapter 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. Insupport of the request ed use on grasses, DuPont has submitted a metabolism study i n canola ( MRID #4 7632210) , along with a justification ( MRID #4 7632212 ) to cite existing data to fulfill nature of the residue data requirements in support of proposed tolerances on grass commodities . Co rn Summary : Greenhouse - grown corn at the 4 - to 5 - leaf stage received a single application of [py

ridine - 2 - 14 C] - nicosulfuron or [py rimidine - 2 - 14 C] - nicosulfuron at 0.063 lb ai/A (0.7 X the maximum proposed seasonal application rate on grasses) . Samples of co rn whole plant wer e collected at PHI s of 0, 7, 14 and 30 days, silage samples were collected at a PHIof 49 days, while grain, cob, and stalk (stover) samples were collected at a PHIof 113 days (maturity ). Based on the results of the nicosulfuron metab olism study in corn, the metabolism of nicosulfuron proceeds predominantly via two mechanisms , which are (1) the hydrolysis of the sulfonylurea bridge yielding py ridine sulfonamide (IN - V9367) and py rimidine amine (IN - J290) , and (2) the hydroxylation of nic osulfuron at the 5 - position (IN - 70940) of the py rimidine 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 analy

zed because these contained <0.005 ppm total [ 14 C ] - equivalents of nicosulfuron. Py ridine sulfonamide was present in the whole plant (0 - to 30 - day

PHI) , in silage (49 - day

PHI), and fodder and stover (11 3 - day PHI). The analyses show ed that nicosulfuron gradually decrease d during the corn growing season , and wa s present in very low levels at maturity . However, residues of IN - V9367 beg an at day 0 , and we re detected in the whole plant and stalk at maturi ty (113 - day PHI). These residues we re higher than the detected residues of the nicosulfuron. IN - J290 wa s further metabolized toNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 12 of 40 IN - 70940 and its glucoside, but these metabolites we re not detected in the whole plant (49 - day PHI) , or in fodder or stover (1 1 - day PHI). Canola (MRIDs #47632210 and 47632211 ) : DuPont has submitted a study investigating the metabolism of [py

ridine - 2 - 14 C] - nicosulfuron (specific activity 62.9 μCi/mg ) and [py rimidine 2 - 14 C] - 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 NI S 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 (py ridine label) or 0.079 lb ai/A (py rimi dine label). The exaggerated application rates used in the study are roughly 1 X the maximum proposed season al rate on grass es . 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 (py ridine label) and 93 days (py rimidine label) after application , and we re separated into foliage, pods and seed s . The petitioner stated that mature plants were allowed to dry down for approximately 10 days before the f inal harvest. The in - life and analy tical 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 r adioactivity, were 0.125, 0.099 and 0.086 ppm in immature canola foliage , respectively , harvested 0, 10 and 30 days following application of [py ridine - 2 - 14 C] - 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 seed s . Following application of [py rimidine - 2 - 14 C] - nicosulfuron at 0.026 lb ai/A, TRR were 0.1 37, 0.080 and 0.074 ppm , respectively , in i mmature foliage harvested 0, 10 and 30 days after treatment, and 0.018, 0.070, and < 0.010 ppm in mature foliage, pods and seed s , respectively . Following exaggerated - rate treatments of the test substances at 0.085 lb ai/A (py ridine label) or 0.079 lb ai/A (py rimidine label), TRR were 0.447, 0.287, and 0.285 ppm in py ridine label 0 - , 10 - and 30 - day

imm ature foliage, respectively , and 0.296, 0.159 and 0.249 ppm in py rimidine - label 0 - , 10 - and 30 - day immature foliage, respectively . In mature matrices, TRR were 0.078, 0.238 and 0.014 ppm in py ridine - label foliage, pods and seed s , respectively , and 0.055, 0.207 and 0.015 ppm in py rimidine - label foliage, pods and seed s , respectively . Based on the low residues in seed s , the petitioner concluded that residues of nicosulfuron and its metabolites are not readily translocated to seeds . Itwas note d that canol a seed samples were not initially subjected to extraction or characterization procedures ( MRID #4 7632210) because TRR were < 0.010 ppm; however, based on preliminary

results from the crop field trials, the petitioner subsequently decided that further invest igation was required ( MRID #4 7632211). 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 pod s, and at the exaggerated rate only for seeds ) , extraction withNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 13 of 40 acetone/0. 1M ammonium carbonate released 58 - 65% TRR (py ridine label) and 47 - 50% TRR (py rimidine label) from f

oliage, 57 - 77% TRR (py

ridine label) and 39 - 63% TRR (py rimidine label) from pods, and 61 - 66% TRR (both labels) from seeds . Extraction procedures were slightly more successful for py

ridine - label matrices than for py rimidine - label matrices, except with seeds . Non - extractable residues accounte d for ≤13% TRR (≤0.032 ppm) in immature foliage (both labels and rates). In mature matrices following nominal - rate applications, non - extractable residues for both labels accounted for 35 - 50% TRR (0.009 - 0.012 ppm) in foliage, and 43 - 61% TRR (0.043 - 0.053 pp m) in pods; seeds w ere 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 c oncludes 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 cons idered by

HED to be a significant food or feed item of canola. Residu es were identified, quantitated and confirmed by HPL C 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 ( LS C ) . 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 ha rvest intervals for both labels. R esidues 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 py ridine - ring metabolite I

N V9367 , and the py

rimidine - ring metabolite s I N - H1043 or I

N - J290 were the major identified residues in mature fo liage, pods and seeds from the respective labels. I N - V9367 accounted for 24 - 28%, 23 - 24%, and 18% TRR in py ri dine - label mature foliage, pods and seeds , respectively , but was present at lo wer levels in immature foliage (3 - 28% TRR). Metabolite I N - H1043 accounted for 15 - 16% and 4 - 7% TRR in py rimidine - 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 I

N - J290 was the major identified residue in py rimidine - 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, Met abolite I

N - 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). Remain ing residues were characterized as unknowns, and accounted for no more than 20% TRR , or 0.031 ppm , in any matrix. RAB2 c oncludes that the petitioner has adequately identified the residues of nicosulfuron in canola matrices. In itial 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 seedNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 14 of 40 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 co ncludes 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 submi tted limited storage stability data in support of the storage duration s 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 m etabolite profiles obtained for seeds were similar to those observed in foliage and pod s, despite the long storage duration of seed samples. Based on the canola metabolism study , the petitioner proposed th at n icosulfuron was metabolized in canola primarily by hydroly tic cleavage of the sulfonylurea linkage to form I N V9367 and I

N - J290. Subsequent demethylation of I N - J290 formed I

N - H1043 and , possibly , other polar components. Other metabolic reactions include the hydroxylation at the 5’ position of the py rimidine ring to form I

N - 70940 , and conjugation of I N - 70940 with glucose to form the glucoside. Justification to Cite Existing D ata ( MRID #4 7632212) : 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 grass es . The discussion addresses the following points:

1 . T he metabolic pathway for nicosulfuron is similar in corn and canola ; metabolite level s were generally low (< 0.010 ppm at 30 days after applicat ion) , except for residues of I N 70940 in immature foliage . 2 . I dentified metabolites were not found to be active in DuPont’s herbicidal, fungici dal and insecticidal screening. 3 . S ignificant unidentified metabolites in the corn study were short lived, generally

decreasing to < 0.010 ppm within 14 days of application, and were generally more polar than the parent. 4 . F ormation of new metabolites given the proposed 0 - day PHI for grass would be unlikely , and if new metabolites were generated, their concentratio n would be expected to be small. 5 . Under the intended use pattern on grass es , forage could be grazed from 0 - 30 days after application, and concentrations of metabolites, including I N - V9367 were roughly ≤ 0.010 ppm at the 30 - day

PHI in corn forage . 6 . And, a s a member of the grass family ( Graminaceae ), corn is suitable as a representative of forage and rangeland grasses.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 15 of 40 Conclusions : The available corn metabolism study, and the s ubmitted canola meta bolism 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 t he 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 use s 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 requir ed because , at the proposed treatment rate for corn, grain contained no detectable residues of nicosulfuron (<0.05 ppm) or any significant metabolites , as demonstrat ed by the plant metabolism study . The Agency has previously concluded that there was no reasonable expectation of finite residues (40 CFR §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 [py ridine - 2 - 14 C] - nicosulfuron or [py rimidine - 2 - 14 C] - nicosulfuron at 60 ppm ( approximately 4 - 14X the dietary

burden to cattle) . Samples of milk were collected daily . The animals were sacrificed with in 24 hours of the final dose, and tissue sample s, including liver, kidney , fat and muscle, were collected. The maximum TRR in milk (py rimidine label only

) were 0.03 ppm. In tissue s , liver had the highest TRR (0.1 ppm; py ri midine label), while TRR in o ther tissues wer e ≤0.07 ppm; no liver sample was analy

zed for the py

ridine - label goat. The only matrix subjected to characterization and

/ or identification procedures was py rimidine - label liver. HPL C analysis indicated that >50% TRR was parent, while the remaining radioa ctivity 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 py ridine sulfonamide (IN - V9367) and py rimidine 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, o xidation and conjugation at the 5 - position of the py rimidine ring.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 16 of 40 Conclusion s: 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 enf

orcement , 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 remain s 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 ( P lant C om mo dities ) DER for MRIDs # 47632207 and 47632208 ( L ivestock C om mo dities ) HED Chapter of the RED (D302694; D. Hrdy; 30 November 2004) Residue Chemistry Mem o ( DEB s # 5324 - 5326 and 6501 - 6503; J. Stokes ; 4 May 1990) Plant Commodities Enforcement and Dat

a C ollection M

ethods : An HPL C enforcement analy tical 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 o f PAM -II . An asterisk indicates that th e method has been submitted to EPA but not compiled in PAM -II . Under the current action, DuPont has submitted an HP LC /MS/MS method, DuPont 17928, for the determination of residues of nicosulfuron and its metabolite , IN - V9367 , in grass forage and hay . T he 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 val idation 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 ce ntrifuged 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 analy tes are not retained on the Envi - Carb cartridge; residues are eluted from the Oasis cartridge with methanol. The purified eluates are evaporated to dry ness under a stream of nitrogen, and reconstituted in methanol/10 mM ammonium formate ( 1 : 1 9, v:v) , then filtered for analysis by HP LC /MS/MS. The method monitors two ion transitions for each analy te. The L OQ is 0.010 ppm for each analy te in grass forage and hay . The method was adequately validated , using samples of grass forage and hay fortified at the method L OQ and 10 X the L O Q (0.010 and 0.10 ppm). Recoveries from grass forage and hay were within the generally recognized acceptable range of 70 - 120% . Recover y 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 . Recover y ranges from grass forage and hay , respectively , were 73 - 114% (with a mean of 98% ,Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 17 of 40 and standard deviation of 14.1 %) , and 80 - 106% (with a mean of 91% , and standard devi ation of 8.6 %) for I

N - V9367 . Itwas note d that the fortification levels used in method validation were not adequate to bracket expected residues in grass forage and hay . H owever, the fortification levels used in the method validation conducted concurrent ly 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 analy te in question should fall within ±30% of the average ratio for all calibration standards in the sample set. No radiovalidation dat a were submitted with the method; however, the petitioner cited previously

submitted radiovalidation data generated in conjunction with the corn metabolism study ( MRID #4 1082626). According to the petitioner, extractio n 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 co rn 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 extract ion 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 sub mitted , reflecting adequate recoveries from grass forage and hay fortified at the L OQ and 10 X 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

d uring the conduct of the study . These changes have not ye t been made to the method by the petitioner. All of these revisions should be incorporated into the method. T he method used for sample analysis in the grass field trials reflected the changes re commended in conjunction with ILV of the method, in addition to other minor modifications. Conclusion s: The submitted data are tentatively adequate to satisfy

data requirements for residue analy

tical 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 I N V9367. For method DuPont - 17928 to be suitable for enf orcement 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 b y the developing laboratory , by

an independent laboratory, and in conjunction with the grass field trials. When theNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 18 of 40 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 C ollection M

ethods: DuPont has submitted an HP LC /MS/MS method, DuPont - 17927, for the determination of residues of nicosulfuron and its metabolite , IN V9367 , in livestock commodities. The method was used for data collection in the cow feeding study . DuPont is proposing this method as an enforcement method , and has submitted method val idation data , and an ILV of the method. Briefly , samples of milk, cream and egg s are mixed with water followed by aceto nitrile (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 dry ness 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 dry ness under a stream of nitrogen, and reconstituted in methanol/ 10 mM ammonium formate ( 1 : 1 9, v:v) , then filtered for analysis by HP LC /MS/MS. Alternatively , extracts (without SPE clean - up) may be filtere d through 0.20 - to 0.45 - μm filters, diluted 20 X with methanol/ 5 mM ammonium formate (1 : 1 9, v:v) , and analy

zed directly

on a sensitive HP LC /MS/MS system. The method monitors two ion transitions for each analy te. The L OQ is 0.010 ppm for each analy te in liv estock commodities. The method was adequately validated using samples of milk, cream, egg s , and beef muscle, kidney , liver, and fat fortified at roughly the LOQ and 10 X the L OQ (0.011 ppm and 0.11 ppm for nicosulfuron , and 0.012 and 0.12 ppm for I N - V936 7); it was note d that only summary data were provided for egg s . Recoveries from livestock commodities were within the generally recognized acceptable range of 70 - 120% for both analy tes . Using the standard method procedures, overall recovery ranges from m ilk 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 I N - V9367. Using the alternative procedures, overall recovery ranges from milk and tiss ues 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 egg s , 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 I N - V9367. Using the alternative procedures, overall recovery ranges from egg s 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 I N V9367. No confirmatory

method was submitted. The petitioner stated that confirmation of any identified peak was based on detection and relativ e 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 theNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 19 of 40 calibration curv e. 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 analy te in question should fall within ±30% of the average ratio for all calibration standards in the s ample 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 #4 1082627) , in which a sample of liver from a goat dosed with [ py rimidine - 2 - 14 C] - 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 egg s and tissues should be conducted . A success ful ILV of the enforcement method (alternate procedures) was submitted reflecting adequate recoveries for milk, cow liver, and egg s fortified at the L OQ and 10 X LOQ (0.010 and 0.10 ppm). Itwas note d 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 analy

tical methods for livestock commodities, pending submission of additional supporting data and information. RAB2 concludes that method DuPont - 1792 7 is acceptable for determination of nic osulfuron, the ROC in livestock commodities, as well as for determination of metabolite I

N - V9367. For method DuPont - 1792 7 to be suitable for enforcement purposes, supporting raw data for method validation with egg s should be submitted . Inaddition, the p etitioner 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 f eeding 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 te sted 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). N one of the multiresidue methods was applicable to nicosulfuron. These data were forwarded to FDA . The HED C hapter of the RED noted that nicosulfuron should be recoverable by Protocol G , which was developed subsequent to multiresidue methods testing for nicosulfuron.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 20 of 40 860.1380 Storage Stability Residue Chemistry Mem o D338945 and D 342602 ; A. Parm ar ; 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 trial s 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 I N - 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 . Conclusion s: 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 c orrections 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 I

N - 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 duratio ns 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 I

N - V9367 in tissues is in progress , and will be sub mitted upon completion . Conclusions: No storage stability data are available reflecting the storage stability of nicosulfuron or metabolite I N - V9367 in milk or livestock tissues. The petitioner should submit the outstanding storage stability study , re flecting storage stability of nicosulfuron and I

N - 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 .Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 21 of 40 860.1460 Food Handling The propos ed 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 nico sulfuron were near or below the L OQ (<0.05 ppm) in corn forage, silage, fodder and grain following application at 0.063 or 0.125 lb ai/A (1X or 2 X the maximum use rate on corn) , n or in grain from the processing study following application at 8 X . In the HED Chapter of the RED , HED concluded that based on the L OQ, the goat metabolism study was conducted at a feeding level of 1200 X, 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 f rom N icosulfuron Residues. Feedstuff Type 1 % Dry Matter 2 % Diet 2 Recom me nded 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 -- -- 1 00 -- 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 BURDE N -- -- 100 -- 0.075Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 22 of 40 TABLE 4 Calculation of Dietary Burdens to Livestock f rom N icosulfuron Residues. Feedstuff Type 1 % Dry Matter 2 % Diet 2 Recom me nded Tolerance (ppm) Dietary Contribution (ppm) 3 Swine Field corn grain CC 88 85 0.10 0.085 PC not registered PC -- 1 5 -- -- TOTAL BURDEN -- -- 100 -- 0.085 1. R = Roughage , CC = Carbohydrate C oncentrate , PC = Protein C oncentrate. 2. OPPTS Residue Chemistry Test Guideline 860. 1000 , Table 1 Feedstuffs ( June 2008 ). 3. Contribution = ([tolerance ÷ %DM] x %diet) for beef and dairy cattle . C ontribution = ([tolerance] x %diet) for poultry and swine. DuPont has submitted a ruminant feeding study with nicosulfuron. Nicosulfuro n 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 le vels were 19.63, 48.79, 146.89 and 489.20 ppm. The dose rates correspond to roughly 4.5 X , 11 X , 3 4 X and 112 X the dietary burden to beef cattle, and roughly 1.2 X , 3.0 X , 9.0 X and 30 X 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 s amples 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 analy zed. Skim milk and cream samples were prepared from milk collected on Days 14 and 21. Milk samples from the depuration grou p collecte d on Days 28, 29, 31, 33 and 35 were analy zed. 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 (L OD); the second cow from the depuration group was sacrificed on Day

39. Samples of live r, kidney , muscle (round, flank and loin) and fat (omental, renal and subcutaneous) were collected from all cows . Samples of milk and ti ssues were analy zed for residues of nicosulfuron and I N - V9367 using adequate HP LC /MS/MS method s, DuPont - 17927 (milk, cream and skim milk) , or an ABC method 63236 - MI(tissues). The methods are essentially identical. T he LOQs were 0.010 ppm for each analy

t e in milk and tissues , and the LODs were 0.003 for each analy te 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 duration s and conditions for tissues; the petitioner stated that a storage stabili ty study for nicosulfuron and I

N - V9367 in tissues is in progress. Residues of nicosulfuron and I N - V9367 were comparable in livestock commodities . R esidues of I

N - V9367 were higher than residues of nicosulfuron in milk, cream, skim milk, and muscle, whil e residues of nicosulfuron were higher than residues of I N - V9367 in remainingNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 23 of 40 tissues (liver, kidney and fat). Detectable residues of nicosulfuron and I N - V93 67 were observed in milk, cream and skim milk at all f eeding levels examined (50, 150 and 500 ppm) . Residues of nicosulfuron and I

N - 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 <0.0 10 - 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. C orresponding residues of I N - V9367 were 0.011 - 0.016 and 0.014 - 0.019 ppm at the 50 - ppm dosin g 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. Intissues, 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 I N - V9367 were observed in tissue at all feeding levels , except in muscle (I N - V9367) and fat (both analy tes) 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 I N - V936 7 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 I N - V9367 wer e 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 - p pm feeding levels, respectively ; corresponding residues of I N - V9367 were <LOQ, 0.010 - 0.016, 0.023 - 0.033, and 0.089 - 0.11 ppm . Infat, 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 I N - V9367 were <LOQ, ≤0.010, <0.010 - 0.014, and 0.022 - 0.046 ppm. Inthe depuration study , reflecting dosing at 500 ppm, residues were non - detectable in milk by sampling Day

31, and in tissues by

sampling Day

33. Conclusion s: The submitted dairy cow feeding study

is tentatively

acceptable , pro vided the outstanding storage stability data confirm that residues of nicosulfuron and I N - 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. Sampl es were analy zed for residues of nicosulfuron, the ROC , as well as for residues of metabolite I N - V9367 , using an acceptable method. The lowest dosing level corresponds to 1.2 X the dietary burden to dairy

cattle, and the highest dosing level corresponds to 30 X the dietary burden t o dairy

cattle. Detectable residues of nicosulfuron were observ ed at feeding levels of 50, 150 and 500 ppm in milk, skim milk, and cream , and in tissue s 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 1 X feeding level for dairy cattle (see Table 5 , below ) , maximum expected residues of nicosulfuron would be 0.007Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 24 of 40 ppm in milk, 0.013 ppm in liver, 0.053 ppm in kidney , 0.008 ppm in muscle, and 0.00 8 ppm in fat. T he data indicate that tolerances are needed in milk, and in the muscle and fat of cattle, goat, horse, and sheep at the L OQ of 0.01 ppm , and in meat by products at 0.05 ppm. A tolerance is not ne eded in milk fat , because residues did not concentrate in cream. TABLE 5 Summary of Residue Data fromRuminant Feeding Study with Nicosulfuron. Matri x Maxim um R esidues (ppm) at E ach D osing L evel Residues A djusted to 1 X F eeding Level for Dairy C attl e* 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 0.0 11 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 lis ted in the text above Table 5 (based on the actual dosing levels ) we re used for calculatin g the adjusted residues (1.2X, 3.0X, 9.0X and 30X) . Tolerances are not needed in hog commodities because there are n o 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 1 X feeding level, maximum residues of 0.0003 ppm in swine tissues (kidney ) would be much lower than the L O D (0.003 ppm) . Because there are no poultry feed items associate d 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 reflectedNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 25 of 40 application to the representative commodities of grass f orage, 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 app lication) , 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 0.7 X the proposed maximum seasonal rate ). Grass samples were har vested 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, 1 X rate ). RTI s 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 , 1 X rate ). An NI S or COC was added to the spray mixture for a ll applications at eight trial sites (except that ammonium sulfate fertilizer was used instead of the NI S/COC for the second application, Treatment 1b, at one site ), and ammonium sulfate or urea/ ammonium nitrate fertilizer was added to the spray mixture in stead of the NI S/COC for all applications at four trial sites . Samples of grass forage and hay were harvested at a 0 - day PHIfor each treatment. H ay samples were allowed to dry in the field for 2 - 8 days before collection. Samples of grass forage and hay were analy

zed for residues of nicosulfuron and I N V9367 using an adequate HP LC /MS/MS method , DuPont - 17928. The L OQ is 0.010 ppm for each analy

te in grass forage and hay . Samples of grass forage and hay were stored frozen for durations of up to 293 d ays (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 re sults 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 I N - 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 I N - 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 - 0.0 92 lb ai/A, maximum residues of nicosulfuron were 8.2 ppm in forage and 18 ppm in hay ; maximum residues of I N - V9367 in forage and hay were 0.59 and 1.2 ppm, respectively .Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 26 of 40 TABLE 6 Summary of Residue Data fromGrass Field Trials with Nicosulfuron (0.088 l b ai/A Total

Use Rate, 0 - day PHI). Crop Matrix Treatm ent;

Total Use Rate (lb ai/A) PHI 1

( D ays) Residue Levels (ppm) n Min. Max. HAFT 2 Median Mean Std. Dev. Nicosulfuron Grass forage 1 application;

0.056 - 0.061 0 24 0.032 5.7 5.0 3.7 3.5 1.3 Gr ass hay 0 [2 - 8] 24 0.11 10 9.3 6.2 5.5 3.2 Grass forage (2 nd cutting) 2 applications;

0.085 - 0.091 0 24 0.53 3.6 3.6 1.9 1.8 0.1 Grass hay (2 nd 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 (2 nd cutting) 2 applications;

0.085 - 0.091 0 24 0.0 24 0.26 0.19 0.092 0.10 0.05 Grass hay (2 nd 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 NI S , 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 a s an adjuvant. H owever, maximum residues of I

N - V9367 were observed only in samples following applic ation with an NI S or COC as a spray

adjuvant. L ikewise, spray volumes did not appear to have a significant impact on residues of nicosulfuron n or IN - V9367 in forage and hay . Itwas noted that the petitioner provided data indicating that hay samples fro m 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 860.10 00 recommends a moisture content o f 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 grass es , and samples were analy zed 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 isNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 27 of 40 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 tolerance s for residues of nicosulfuron in grass forage at 9.0 ppm , and in grass hay at 25 ppm. Itwas note d that the submitted data are sufficient with respect to the number of field trials, varieties used, and residues found by variety to support crop gro up 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 grass es . Therefore, data requirements for processed food and feed are not relev ant to this tolerance petition. 860.1650 Submittal of Analytical Reference Standards An analy tical standard for nicosulfuron is currently in the EPA National Pesticide Standards Repository , per communication with Dallas Wright, o f the Biological and Economic Analysis Division’s (BEAD’s) Analy tical Chemistry

Branch (ACB ) , on 1 June 20 09 . However, the standard expire d on 14 October 20 09 . The registrant should either recertify the lot in the repository , and send in an updated certi ficate of analysis (COA), or submit a new standard (having a different lot number) if the previous lot will not be recertified. I f 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 Analy tical Chemistry

L ab ( located at Fort Meade ) , to the attention of Theresa Cole , at the following address: USEPA National Pesticide Standards Repository /Analy tical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 ( Please n ote 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 [py

ridine - 2 - 14 C] - nicosulfuron or [py rimidine - 2 - 14 C] - nicosulfuron to the soil at 0.062 lb ai/A ( 70 g ai /ha , roughly 0.7 X the maximum propos ed seasonal application rate on B ermuda grass) . The study w as reviewed by the Environmental Fate and Effects DivisionNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 28 of 40 ( EFED ) in E. Regelman’s memo of 1 June 19 90. Rotational crops were planted 1 , 4 and /or 10 months after application as follows:

1. S oy beans at 30 and 120 days , and 10 months. 2. L ettuce and wh eat at 120 days , and 10 months . 3. And, radishes at 10 months. All crops were harvested at maturity . The data indicat ed that metabolite s and / or degradates containing the py ridine ring are more readily

taken up by

plants than those containing the py rimidine ring. Residues of the py rimidine amine (IN - J290) were not detected in soils or plants, even though this metabolite is a major metabolite/degradate of nicosulfuron. With the py rimidine - labeled material, total residues were lower, and the only

ide ntified metabolite/degradate was N - desmethyl nicosulfuron, which was higher in forage and hay than in seeds. Maximum total residues were observed in soy bean forage , hay

and seed when the py

ridine - labeled material was used, but the amount of residues decre ased with the aging period of the soil. The major metabolite detected was py ridine sulfonamide (IN - V9367) . Maximum total residues were also observed in wheat straw and chaff when the py

ridine - labeled nicosulfuron was used; py ridine 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 hydroly

zed rapidly

in acidic soil s, with the formation of py ridine sulfonamide , and py rimidine amine as the metabolites, which are then taken up by the plant. A 10 - month PBI was recommended , based on phy totoxic 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 Mem o D208793 ; G. Kram er; 16 June 19 95 Three limited field trials on soy bean s were conducted in IL, DE and MS in 1991. The 75% WDG formulation of nicosulfuron was applied , at the rate of 0.0 63 lb ai/A , to corn at the 10 - leaf stage. The application rate corresponds to 0. 7 X the maximum proposed seasonal application rate to grasses ( 1 X the maximum registered rate for corn) . The corn was cut , and soy beans were planted 7, 15 and 30 days after treatment (DAT) . Soy bean forage and hay were harvested 39 - 73 DAT; soy bean grain and straw, at 116 - 160 DAT. No measurable residues (<0.05 ppm) of nicosulfuron were found in any soy bean sample. No residues of the major metabolite , I

N - 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 soy beans. EFED also approved reducti on of the PBIfor wheat from 10 months to 4 months.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 29 of 40 Conclusion s: 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 soy

bean s 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. Inconsideration 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 t uber vegetables, leafy

vegetables or soy

bean s , 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 co nsistent 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 sh ould 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 - py

rimidinyl) amino] carbonyl] amino] sulfonyl] -N,N

- dimethyl - 3 - py

ridinecarboxamide). The tolerances proposed by DuPont are listed in Table 7 (below) , along with the tolerance levels recommended by

RAB 2. 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 purpo ses of establishin g tolerances i n 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 th e liver, kidney , muscle and fat of cattle, goat, horse and sheep. Tolerances are not needed in milk fat , n or in swineNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 30 of 40 commodities. T olerances in milk, meat, and fat should be set at 0.01 ppm ( the LOQ) , and in meat by products at 0.05 ppm. No Codex or M exican MRL s are established for residues of nicosulfuron ; Canadian MRL s 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 Sum m ary for Nicosulfuron. Com mo dity Proposed Tolerance (ppm) Recom me nded

Tolerance (ppm) Com me nts ; C orrect Commodity D efinition 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 bur den t o 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 0.01Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 31 of 40 References Nicosu lfuron. 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 Comment s on Independent Laboratory Validation of DPXV9360 Methodology for Corn Fodder. ; DEB Numbers 5234 - 5326 and 6501 - 6503; J. Stokes ; 4 May 19 90 . ID# 00352 - 00560. Review of label amendment for nicosulfuron (Accent SP Herbicide) to re duce plantback interval for soybeans. Case 026774. CBTS# 14652. ; D 208793; G. Kramer ; 16 June 19 95 . Nicosulfuron HED Chapter of the Reregistration Eligibility Decision Document (RED). PC Code: 129008, Case #: none. ; D 302694; D . Hrdy , A. Khasawinah, J. Stokes, M. Crowley , and J. Miller, and L . L iu ; 3 0 November 20 04 . 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. ; D 338945 and D342602; A. Parmar ; 18 October 20 07 .

Attachments International Residue L imit Status S heet Appendix I - Chemical Name and Structure Table Appendix II - Tolerance Assessment Calcu lationsNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 32 of 40 

## INTERNATIONAL RESIDUE LIMIT STATUS C AS Nam e: 2 - [[[[(4,6 - dimethoxy - 2 - pyrimidinyl) amino] carbonyl] amino] sulfonyl] -N,N

- dimethyl - 3 - pyridinecarboxamide Com mo n Nam e: Nicosulfuron X Recom me nd ed tolerance s ⁮ Re - evaluated tolerance ⁮ Other Date: 2 1 June 20 09 Codex Status (Maximum Residue Limits) U S Tolerances X No Codex proposal step 6 or above ⁮ No Codex proposal step 6 or above for the crops requested Petition Number: 8F7501 DP Barcode : D 360897 (Decision #404568) Other Identifier: PC Code 12 9008 Res idue definition (step 8/CXL): NA Reviewer/Branch: William T. Drew /RAB2 Residue definition: Nicosulfuron Crop(s) MRL (mg/kg) Crop s Tolerance (ppm) Grass, forage 9.0 Grass, hay 25 Cattle, fat 0.0 1 Cattle, meat byproducts 0.05 Cattle, meat 0.0 1 Goat, fat 0.0 1 Goat, meat byproducts 0.05 Goat, meat 0.0 1 Horse, fat 0.0 1 Horse, meat byproducts 0.05 Horse, meat 0.0 1 Milk 0.0 1 Sheep, fat 0.0 1 Sheep, meat byproducts 0.05 Sheep, meat 0.0 1 Limits for Canada L imits 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.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 33 of 40 Appendix I - Chemical Name and Structure Table APPENDIX I Chemical Nam es and Structures of Nicosu lfuron and Metabolites. Company Code ; Com mo n Nam e Chemical N am e Chemical S tructure Nicosulfuron 2 - [[[[(4,6 - dimethoxy - pyrimidin - 2 - yl) - amino]carbonyl]amino]sulfonyl] - N,N - dimethyl - 3 - pyridinecarboxamide N O N C H 3 C H 3

S NH NH N N O

O C H 3 C H 3 O O O

IN - V9367 ; pyridine sulfonamide [2 - aminosulfonyl] -N,N - dimethyl - 3 - pyridinecarboxamide

N O N C H 3 C H 3

S NH 2 O O

IN - 70940 and its glucose conjugate 2 - [[[[(4,6 - dimethoxy - 5 - hydroxy pyrimidin - 2 - yl)amino]carbonyl]amino] - sulfonyl] - N,N - dimethyl - 3 - pyridinecarboxamide N O N C H 3 C H 3

S N H N H N N O

O C H 3 C H 3 O O O

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

O C H 3 C H 3 N H 2

IN - H1 043 2 - amino - 4,6 - dihydroxypyrimidine N N O H

O H N H 2Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 34 of 40 APPENDIX I Chemical Nam es and Structures of Nicosu lfuron and Metabolites. Company Code ; Com mo n Nam e Chemical N am e Chemical S tructure N - desmethyl nicosulfuro n*

N O N H C H 3

S N H N H N N O

O C H 3 C H 3 O O O

* Tentative structure wa s determined by the study reviewer , as the original review was unavailable.Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 35 of 40 Appendix II - Tolerance Assessment Calculations The dataset used to establish tol erance s for nicosulfuron i n 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 Tri al Data (SOP), the field trial application rates and PHI s 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) . T he 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 calculation s . All field trial sample results for grass forage and hay were above the LOQ (LOQ = 0.01 0 ppm). For gra ss forage, v isual inspection of the lognormal probability plot (Figure II - 1 , below ) , and the results from the approximate Shapiro - Francia test statistic (Figure II - 2 , below ) indicate d that the dataset was reasonably lognormal. For grass hay , v isual inspec tion 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 nicosul furon on grass forage represent a large dataset ( 24 samples) , and are reasonably lognormal, the minimum of the 95% upper confidence limit (UCL) on the 95 th percentile , and the point estimate of the 99 th percentile , should be selected as the tolerance value . Using the rounding procedure as outlined in the SOP, both the 95% UCLon the 95 th percentile , and the point estimate of the 99 th percentile , round to the value 9 .0 ppm (Figure II - 2 ) . T herefore, 9.0 ppm is the recommended tolerance level for nicosulfuro n i n grass forage . Since the field trial data for nicosulfuron on grass hay are not lognormal, the upper bound on the 89 th 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 89 th percentile rounds to the value 25 ppm . T herefore, 25 ppm is the recommended tolerance level for nicosulfuron i n grass hay .Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 36 of 40 TABLE II - 1 Residue Data U sed to Calculate T olerance S for Nicosulfuron in Grass Forage and H ay . 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 #4 76 32204 MRID #4 7632204 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 0.2 6 6.2 12 4.9 12 4.5 11 4.9 1 0 5.9 14 6.6 8.7Nicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 37 of 40 Figure II - 1 Lognormal P robability P lot of N icosulfuron Field T rial Data (Grass F orage ) . Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 9.0000

4.5000

2.2500 y = 0.2108x + 1.6982 R 2 = 0.979

PercentilesConcentrations EPA Nicosulfuron Grass forage 0 Days 0.088 lb ai/A E.I. DuPont de Nemours and CompanyNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 38 of 40 Figure II - 2 Tolerance S preadsheet S ummary of Nicosulfuron F ield Trial D ata (G rass

F orage ) . 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+3SDNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 39 of 40 Figure II - 3 Lognormal P robability P lot of N icosulfuron Field Trial D ata (G rass H ay) . Lognormal Probability Plot

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

PercentilesConcentrations EPA Nicosulfuron Grass hay 0 Days 0.088 lb ai/A E.I. DuPont de Nemours and CompanyNicosulfuron Summary of Analytical Chemistry and Residue Data DP Barcode: D36 0897

Page 40 of 40 Figure II - 4 Tolerance Spreadsheet S ummary of N icosulfuron Field Trial D ata (G rass

H ay) . 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