Document ID: EPA-HQ-OPP-2016-0516-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2018-02-12T05:00Z

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                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                       
                                                  OFFICE OF CHEMICAL SAFETY AND
                                                                                               POLLUTION PREVENTION
                                                                               
MEMORANDUM

Date:	01/03/2018

Subject:	Rimsulfuron. Petition for the Establishment of Permanent Tolerances on Tuberous and Corm Vegetable Subgroup 1C, Small Vine Climbing Fruit Except Fuzzy Kiwifruit Subgroup 13-07F, Low Growing Berry Except Strawberry Subgroup 13-07H, and Seed Crop Ryegrass and Fescue Forage and Hay, and Tolerance Conversion to Citrus Fruit Group 10-10, Pome Fruit Group 11-10, Stone Fruit Group 12-12, and Tree Nut Group 14-12. Summary of Analytical Chemistry and Residue Data.

PC Code:  129009
DP Barcode:  D438170
Decision No.: 519986
Registration Nos.:  352-768; 66222-184
Petition No.:  6E8496
Regulatory Action:   Section 3 Registration
Risk Assessment Type:  NA
Case No.:  NA
TXR No.:  NA
CAS No.:  122931-48-0
MRID No.:  49973401, 49973402
40 CFR: §180.478

From:	Robert McGovern, Chemist
	Risk Assessment Branch III
	Health Effects Division (HED; 7509P)

Through:	Thomas Moriarty, Branch Chief
         Risk Assessment Branch III
         Health Effects Division; HED (HED; 7509P)

To: 	Sidney Jackson, Review Manager Team 05
	Minor Use and Emergency Response Branch
	Risk Management Division (RD; 7505P)

Summary of Submitted Residue Chemistry Studies
OCSPP 860 Series Guideline
MRID Number
Monograph Annex B Reference
Title
860.1500
49973401
B.7.6.
Rimsulfuron: Magnitude of the Residue on Grasses (Seed Crop)
IR-4 PR No. 10657

49973402

Rimsulfuron: Magnitude of the Residue on Cranberry
IR-4 PR No. 07888

                               Table of Contents

1.0	Executive Summary	5
2.0	Regulatory Recommendations	7
2.1	Data Deficiencies/Data Needs	7
2.2	Tolerance Considerations	7
2.2.1	Enforcement Analytical Method	7
2.2.2	Recommended Tolerances	8
2.2.3	Revisions to Petitioned-For Tolerances	9
2.2.4	International Harmonization	9
3.0	Introduction	9
3.1	Chemical Identity	9
3.2	Physical/Chemical Characteristics	10
4.0	Metabolite/Degradate Residue Profile	12
4.1	Nature of the Residue	12
4.1.1 	Summary of Plant Metabolism (860.1300)	12
4.1.3	Summary of Confined Rotational Crops (860.l850)	13
4.2	Comparison of Metabolic Pathways	13
4.3	Residues of Concern Summary and Rationale	13
5.0	Residue Profile	14
5.1	Residue Analytical Methods (860.1340)	14
5.1.1	Data Collection Methods	14
5.1.2	Multi-Residue Methods (860.1360)	15
5.1.3	Tolerance Enforcement Methods	15
5.1.4	Submittal of Analytical Reference Standards (860.1650)	15
5.2	Storage Stability (860.1380)	15
5.3	Residue Data	16
5.3.1	Crop Field Trials (860.1500)	16
5.3.2	New Uses and Crop Group Conversions	17
5.3.3	Field Rotational Crops (860.1900)	19
5.3.4	Processed Food and Feed (860.1520)	19
5.3.5	Meat, Milk, Poultry and Eggs (860.1480)	19
5.3.6	Food Handling (860.1460)	19
5.3.7	Water, Fish, and Irrigated Crops (860.1400)	19
5.4	Food Residue Profile	19
6.0	Tolerance Derivation	20
Appendix A	Harmonization Considerations for Rimsulfuron	22
 
  
1.0	Executive Summary

Rimsulfuron (1-[4,6-dimethoxypyrimidin-2-yl]-3-[3-ethylsulfonyl-2-pyridylsulfonyl]urea) is a
systemic herbicide belonging to the sulfonylurea group of herbicides. Sulfonylureas inhibit acetolactate actohydroxyacid synthase (ALS/AHAS), preventing amino acid synthesis in target pest plants. Tolerances for residues of rimsulfuron have been established under 40 CFR §180.478(a).

Pruvin and Matrix SG are herbicides with active ingredient rimsulfuron for broad control of pest plants in agricultural and non-agricultural applications. 

Proposed Use: IR-4 is requesting a U.S. registration for use of rimsulfuron (end-use product Pruvin) on subgroup 13-07H. The proposed maximum seasonal rate is 0.0625 lbs ai/A, re-treatment interval (RTI) of 21 days and pre-harvest interval (PHI) of 60 days. The proposed foliar application may be made by ground broadcast. This proposed use is supported by data on the subgroup representative crop, cranberries.

IR-4 is requesting a tolerance with regional registration for the use of rimsulfuron (end-use product Matrix SG) on fescue and ryegrass hay and forage for seed crops (non-food, non-feed usage) in US Growing Region 12. The proposed maximum seasonal rate is 0.048 lbs ai/A, with no RTI or PHI. The proposed pre-emergence application may be made by ground broadcast. This proposed use is supported by data on fescue and ryegrass hay and forage. 

IR-4 is requesting crop group conversions from fruit, citrus, group 10 to fruit, citrus, group 10-10, from fruit, pome, group 11 to fruit, pome, group 11-10, from fruit, stone, group 12 to fruit, stone, group 12-12, from nut, tree, group 14 to nut, tree, group 14-12. The proposed use patterns for these group conversions are identical to the current, approved use patterns for the respective original crop groups.

IR-4 is requesting new US registration with tolerance on vegetable, tuberous and corm, subgroup 1C based on previously submitted and reviewed data on the representative crop potato, and on fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F based on previously submitted and reviewed data on the representative crop grape. The proposed use patterns for these subgroups are identical to the current, approved use patterns for the representative commodities (potato and grape, respectively).

IR-4 is requesting removal of tolerances for individual commodities of pistachio, potato and grape pending the establishment of the above new uses and crop group conversions.

Nature of the Residue in Plants: The nature of residues of rimsulfuron in plants is well understood. The major metabolic route of rimsulfuron metabolism/degradation involves sulfonylurea bridge contraction, with sulfonylurea bridge cleavage as a minor metabolic route. The metabolites detected have been determined to be not of toxicological or human health concern. The residue of concern has been determined to be parent rimsulfuron only.

Nature of the Residue in Livestock: The nature of residues of rimsulfuron in animals is well understood and is largely identical to the nature of residue in plants. The major metabolic route of rimsulfuron metabolism/degradation involves sulfonylurea bridge contraction, with sulfonylurea bridge cleavage as a minor metabolic route. The metabolites detected have been determined to be not of toxicological or human health concern. The residue of concern has been determined to be parent rimsulfuron only.

Enforcement Methods in Plants/Livestock: An adequate data collection method, method DuPont method 15033 using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS), is available for determination of residues of rimsulfuron in/on cranberry and grass forage and hay commodities. This method is an improvement over the previous method using the same extraction technique, and this method was used to analyze samples from the field trials submitted with this petition. The limit of quantitation (LOQ) was validated in each matrix included in the field trials with 10 replicates of fortified samples. The independent laboratory verification (ILV) study requirements are waived in accordance with guideline 860.1340 (ii), and the analytical laboratory validation and concurrent recoveries were within the acceptable range (70-120% recovery and >30% RSD). Radiovalidation data are not needed since the extraction solvent for the method is similar to the extraction solvent used in the metabolism studies. 

Multiresidue Methods: The FDA mutli-residue methods (MRM) are not appropriate for analysis or enforcement of residues of rimsulfuron. Rimsulfuron is not recovered in the FDA MRM.

Crop Field Trials: IR-4 has submitted crop field trials for residues of rimsulfuron in/on cranberries and grass forage and hay. No additional data have been submitted in support of the crop group conversions. No additional data have been submitted in support of the new uses on subgroups 1C and 13-07F, IR-4 is relying instead upon previously submitted and reviewed data on the representative commodities of these subgroups. No additional data has been submitted for crop group conversions requested from 10, 11, 12, and 14 to 10-10, 11-10, 12-12, and 14-12, IR-4 is relying instead upon previously submitted and reviewed data on the representative commodities of these groups.

A total of 5 field trials were conducted on cranberries during the 2011 growing season. Results from these trials indicate that residues of rimsulfuron in cranberries are expected to be <LOQ (<0.01 ppm) when treated with rimsulfuron at a maximum seasonal rate of 0.0625 lbs ai/A and 60-day PHI. Decline data of rimsulfuron in cranberries could not be generated because all sample residues were <LOQ, and decline of rimsulfuron cannot be assessed at this time. The tolerance recommendation will require modification based upon recoveries of the concurrent storage stability samples.

A total of 4 field trials were conducted on grass forage and hay during the 2011-2012 growing season. Results from these trials indicate that residues of rimsulfuron in grass forage and hay are expected to be <LOQ (<0.01 ppm) when treated with rimsulfuron at a maximum seasonal rate of 0.048 lbs ai/A and 200-day PHI. Decline data of rimsulfuron in grasses could not be generated because all sample residues were <LOQ, and decline of rimsulfuron cannot be assessed at this time.  

Storage Stability: Storage stability data are sufficient to demonstrate the stability of rimsulfuron in grass forage and hay for up to 813 days under frozen (<=-20ºC) conditions. The storage stability data show that rimsulfuron is not stable in cranberries at 717 days or longer under frozen conditions. The data demonstrate that 50% or more of the residue may be lost at 717 days or longer under frozen conditions. Data were not generated for increments less than 717 days frozen, and no conclusion of a maximum storage stability duration in cranberries can be drawn at this time.

2.0	Regulatory Recommendations

HED has examined the residue chemistry database for rimsulfuron.  Pending submission of revised Section F, there are no residue chemistry issues that would preclude granting the requested establishment of tolerance for residue of rimsulfuron in/on grasses (seed crop) and subgroup 13-07H (using data on the representative crop, cranberry). Previously submitted data is sufficient for crop group conversions (groups 10, 11, 12, and 14 to groups 10-10, 11-10, 12-12, and 14-12), and establishment of tolerances for subgroups 1C (using data on the representative crop, potato) and 13-07F (using data on the representative crop, grape). 

A human health risk assessment is forthcoming.

2.1	Data Deficiencies/Data Needs

None

2.2	Tolerance Considerations

2.2.1	Enforcement Analytical Method

Samples of grass forage and hay and cranberries are analyzed for residues of rimsulfuron using a modification of DuPont method # 15033: "Analytical method for the determination of Rimsulfuron in Watery and Dry Crop Matrices by HPLC/ESI-MS/MS" (A. Pentz, J. Bilas, M. E. Y. Cabusas, 2004).  This method is an improvement upon methods previously evaluated under Rimsulfuron Human Health Draft Risk Assessment for Registration Review (DP# D425703, M. Mercado-Feliciano, K. Rury, M. Negussie, 09/14/2015) and is deemed acceptable for analysis of rimsulfuron residues in crops. Concurrent procedural recoveries in each matrix validate the method for use in grass forage and hay and cranberries.

Briefly, samples were extracted with 0.1M potassium phosphate (pH 7)/ methanol (4:1, v/v).  Cleaned up steps were concluded to be unnecessary and as such omitted. Extract was centrifuged and a portion of this extract was diluted to 10 mL with 5mM ammonium acetate/methanol (4:1 v/v). This portion was passed through a 0.45 um PTFE filter and analyzed for residues of rimsulfuron using HPLC/ESI-MS/MS.  The LOQ for rimsulfuron was 0.01 ppm and the limit of detection (LOD) was established at 0.003 ppm (calculated as 1/3 LOQ).  

2.2.2	Recommended Tolerances
 
Table 2.2.2.1.  Tolerance Summary for Rimsulfuron.
                             Established Commodity
                                  Established
                                Tolerance (ppm)
                             Proposed Commodity[1]
                           IR-4-Proposed Tolerance 
                                     (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments 
                        (correct commodity definition)
                  Tolerance Summary for 40 CFR §180.478 (a)

                                      --
                                      --
Berry, low growing, except strawberry, subgroup 13-07H
                                     0.01
                                     0.02
Cranberry is the representative commodity of the subgroup; this tolerance recommendation is based on cranberry data
Fruit, citrus group 10
                                     0.01
Fruit, citrus, group 10-10
                                     0.01
                                     0.01

Fruit, pome group 11
                                     0.01
Fruit, pome, group 11-10
                                     0.01
                                     0.01

Fruit, stone, group 12
                                     0.01
Fruit, stone, group 12-12
                                     0.01
                                     0.01

Nut, tree, group 14
                                     0.01
Nut, tree, group 14-12
                                     0.01
                                     0.01

Potato
                                      0.1
Vegetables, tuberous and corm, subgroup 1C
                                      0.1
                                      0.1
Potato is the representative commodity of the subgroup; this tolerance recommendation is based on potato data
Grape
                                     0.01
Fruit, small, vine climbing, except fuzzy kiwifruit subgroup 13-07F
                                     0.01
                                     0.01
Grape is the representative commodity of the subgroup; this tolerance recommendation is based on grape data
                  Tolerance Summary for 40 CFR §180.478 (c)

                                      --
                                      --
Fescue, forage
                                     0.01
                                     0.01
Not for food or feed use; region 12 restricted use

                                      --
                                      --
Fescue, hay
                                     0.01
                                     0.01

                                      --
                                      --
Ryegrass, perennial, forage
                                     0.01
                                     0.01

                                      --
                                      --
Ryegrass, perennial, hay
                                     0.01
                                     0.01

The following established tolerances should be removed upon approval of the tolerances in Table 2.2.2.1.

Table 2.2.2.2.  Established tolerances to be Removed upon Establishment of Tolerances in Table 2.2.2.1.
Commodity
                          Established Tolerance (ppm)
Fruit, citrus group 10
                                     0.01
Fruit, pome, group 11
                                     0.01
Fruit, stone, group 12
                                     0.01
Nut, tree, group 14
                                     0.01
Pistachio
                                      0.1
Potato
                                     0.01
Grape
                                     0.01

2.2.3	Revisions to Petitioned-For Tolerances

HED is recommending that tolerances be set for the commodities requested by the registrant at the levels requested, with the following change: the proposed tolerance of 0.01 ppm for subgroup 13-07H should be increased to 0.02 ppm to fully account for residue loss in the field trial samples during freezer storage from the time of harvest to the time of analysis.  Concurrent storage stability samples indicate that as much as half of the residue present in the samples may have been lost between the time of harvest and the time of analysis; therefore, 0.02 ppm (twice LOQ) was selected as the appropriate tolerance for subgroup 13-07H.

2.2.4	International Harmonization

There are no Codex maximum residue limit (MRL) established for residues of rimsulfuron in/on any petitioned commodity. Canadian MRLs have been established for residues of rimsulfuron in/on: lingonberries at 0.01 ppm, which is in harmony with the proposed tolerance for crop group 10-10 at 0.01 ppm; gooseberries at 0.01 ppm, which is in harmony with the proposed tolerance for crop subgroup 13-07F at 0.01 ppm; potato at 0.1 ppm, which is in harmony with the proposed tolerance of 0.1 ppm; and lowbush blueberry at 0.05 ppm, which is not in harmony with subgroup 13-07H proposed tolerance of 0.01 ppm, nor the HED-recommended tolerance of 0.02 ppm. HED has not been petitioned to harmonize with this Canadian MRL, and does not recommend doing so because the data on cranberry as the representative crop of subgroup 13-07H indicates 0.02 ppm is the appropriate tolerance for the subgroup.

2.3	Label Recommendations

None.

3.0	Introduction

Rimsulfuron (1-[4,6-dimethoxypyrimidin-2-yl]-3-[3-ethylsulfonyl-2-pyridylsulfonyl]urea) is a
systemic herbicide belonging to the sulfonylurea group of herbicides. Sulfonylureas inhibit acetolactate actohydroxyacid synthase (ALS/AHAS), preventing amino acid synthesis in target pest plants.

3.1	Chemical Identity

Table 3.1.1.1.  Nomenclature for Rimsulfuron and Metabolites of Interest.
Common name
Rimsulfuron
Identity
N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(ethylsulfonyl)-2-pyridinesulfonamide
CAS no.
122931-48-0
Company experimental name
DPX-E9636
Other synonyms (if applicable)

                                       

3.2	Physical/Chemical Characteristics

Table 3.2.1.1.  Physicochemical Properties of Technical Grade Rimsulfuron.
Parameter
Value
Reference
Melting Point
172-173ºC
DP# 193018, M. Nelson, 11/23/1993;
MRID 47572805;
DP# D425703, M. Mercado-Filiciano, K. Ruru, M. Negussie, 09/14/2015
pH
4.32 to 5.89 (1% dilution in water)

Density
1.5032 +- 0.0016 g/cm[3]

Water solubility
pH 5: 0.135 +- 0.005 g/L (25ºC)
pH 7: 7.3 +- 0.03 g/L (25ºC)
pH 9: 5.56 +- 0.05 g/L (25ºC)
pH 4-4.5: 0.024 +- 0.001 g/L (20ºC)

Solvent solubility (25ºC)
N,N-dimethylformamide                         241 +- 1 g/L
Dimethyl sulfoxide                                  113 +- 3 g/L
Methylene chloride                              35.5 +- 0.4 g/L
Acetonitrile                                          17.2 +- 0.5 g/L
Acetone                                                14.8 +- 0.5 g/L
Ethyl acetate                                       2.85 +- 0.17 g/L
Methanol                                            1.55 +- 0.11 g/L
Toluene                                          0.363 +- 0.022 g/L
Xylene                                            0.093 +- 0.008 g/L
n-Hexane                                                     <0.01 g/L

Vapor pressue (25ºC)
<10[-5] Pa (<10[-7] mm Hg)

Dissociation constant, pKa
4

Octanol/water partition coefficient, Log(KOW)
pH 5: 1.94
pH 7: 0.0342
pH 9: not attempted

UV/visible absorption spectrum
pH 1.80 at 230 nm, ɛ = 1.78 x 10[4] (log ɛ = 4.25) and at 290 mm, ɛ = 1.81 x 10[2] (log ɛ = 2.26)
pH 2.10 at 290 nm, ɛ = 2.03 x 10[2] (log ɛ = 2.31)
pH 5.03 at 240 nm, ɛ = 2.24 x 10[4] (log ɛ = 4.35) and at 290 nm, ɛ = 4.81 x 10[2] (log ɛ = 2.68)

3.3	Pesticide Use Pattern/Directions for Use (860.1200) 

Table 3.3.1.1.  Summary of Proposed Directions for Use of Rimsulfuron.
Applic. Timing, Type, and Equip.
                                  Formulation
                                [EPA Reg. No.]
                                 Applic. Rate 
                                   (lb ai/A)
                          Max. No. Applic. per Season
                          Max. Seasonal Applic. Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                        Use Directions and Limitations
            Berry, Low Growing, Except Strawberry, Subgroup 13-07H 
(Bearberry; bilberry; blueberry, lowbush; cloudberry; cranberry; lingonberry; muntries; partridgeberry; cultivars, varieties, and/or cultivars of these)
Foliar broadcase
PRUVIN Dry Flowable (25% ai)
[66222-184]
                                     0.02
                                       2
                                     0.063
                                      60
21-day retreatment interval (RTI)
                            Fescue, forage and hay
Pre-emergence Ground broadcast
Matrix Wettable Granule (25% ai)
[352-768]
                                     0.063
                                       1
                                     0.063
                                      NA
                                       
application for seed crop only
                           Ryegrass, forage and hay
Pre-emergence Ground broadcase
Matrix Wettable Granule (25% ai)
[352-768]
                                     0.063
                                       1
                                     0.063
                                      NA
application for seed crop only
                          Fruit, Citrus, Group 10-10
(Australian desert lime; Australian finger-lime; Australian round lime; Brown River finger lime; calamondin; citron; citrus hybrids; grapefruit; Japanese summer grapefruit; kumquat; lemon; lime; Mediterranean mandarin; mount white lime; New Guinea wild lime; orange, sour; orange, sweet; pummelo; Russell River lime; satsuma mandarin; sweet lime; tachibana orange; Tahiti lime; tangelo; tangerine (mandarin); tangor; trifoliate orange; uniq fruit; cultivars, varieties, and/or hybrids of these)
Post-emergence ground broadcast or chemigation
Dry Flowable (25% ai)
[352-671]
                                0.032 or 0.063
                                       2
                                     0.063
                                       3
30-day RTI
                           Fruit, Pome, Group 11-10
(apple; azarole; crabapple; loquat; mayhaw; medlar; pear; pear, Asian; quince; quince, Chinese; quince, Japanese; tejocote; cultivars, varieties, and/or hybrids of these)
Post-emergence ground broadcast or chemigation
Dry Flowable (25% ai)
[352-671]
                                0.032 or 0.063
                                       2
                                     0.063
                                       7
30-day RTI
                           Fruit, Stone, Group 12-12
(apricot; apricot, Japanese; capulin; cherry, black; cherry, Nanking; cherry, sweet; cherry, tart; Jujube, Chinese; nectarine; peach; plum; plum, American; plum, beach; plum, Canada; plum, cherry; plum, Chickasaw; plum, Damson; plum, Japanese; plum, Klamath; plum, prune; plumcot; sloe; cultivars, varieties, and/or hybrids of these)
Post-emergence ground broadcast or chemigation
Dry Flowable (25% ai)
[352-671]
                                0.032 or 0.063
                                       2
                                     0.063
                                      14
30-day RTI
                            Nut, Tree, Group 14-10
(African nut-tree; almond; beechnut; Brazil nut; Brazilian pine; bunya; bur oak; butternut; Cajou nut; candlenut; cashew; chestnut; chinquapin; coconut; coquito nut; dika nut; ginkgo; Guiana chestnut; hazelnut (filbert); heartnut; hickory nut; Japanese horse-chestnut; macadamia nut; mongongo nut; monkey-pot; monkey puzzle nut; Okari nut; Pachira nut; peach palm nut; pecan; pequi; Pili nut; pine nut; pistachio; Sapucaia nut; tropical almond; walnut, black; walnut, English; yellowhorn; cultivars, varieties, and/or hybrids of these)
Post-emergence ground broadcast or chemigation
Dry Flowable (25% ai)
[352-671]
                                0.032 or 0.063
                                       2
                                     0.063
                                      14
30-day RTI
                    Vegetable, Tuberous and Corm, Group 1C
(Arracacha; arrowroot; artichoke, Chinese; artichoke, Jerusalem; canna, edible; cassava, bitter and sweet; chayote (root); chufa; dasheen; ginger; leren; potato; sweet potato; tanier; turmeric; yam bean; yam, true)
Ground or aerial chemigation
Dry Flowable (25% ai)
[352-671]
                                     0.023
                                       2
                                     0.039
                                      30

     Fruits, Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F
(Amur river grape; gooseberry; grape; kiwifruit, hardy; maypop; schisandra berry; cultivars, varieties, and/or hybrids of these)
Post-emergence ground broadcast or chemigation
Dry Flowable (25% ai)
[352-671]
                                0.032 or 0.063
                                       2
                                     0.063
                                      14
30-day RTI

The proposed labels are adequate to evaluate against the petitioned uses. 

4.0	Metabolite/Degradate Residue Profile

4.1	Nature of the Residue

4.1.1 	Summary of Plant Metabolism (860.1300)
MARC Decision Memo, 11/FEB/1998, L. Cheng, G.J. Herndon; and DP# 200158, M.J. Nelson, 29/MAR/1994
MARC Briefing Memo, 04/FB/1998, L. Cheng; and DP# 200157, M.J. Nelson, 17/MAR/1994

The nature of the residue in plant commodities is adequately understood based on metabolism studies conducted with rimsulfuron, labeled in the pyridine or pyrimidine ring, in field corn, potatoes and tomatoes. The major metabolic route of rimsulfuron metabolism/degradation involves sulfonylurea bridge contraction, with sulfonylurea bridge cleavage as a minor metabolic route. The metabolites detected were IN-70941, IN-70942, IN-E9260, IN-J290, IN-T5831 (potato), IN-JF999 (tomato), and unresolved polar/nonpolar products. The residue of concern has been determined to be rimsulfuron.

4.1.2	Summary of Livestock Metabolism (860.1300)
MARC Decision Memo, 11/FEB/1998, L. Cheng, G.J. Herndon; and DP# 200158, M.J. Nelson, 29/MAR/1994
MARC Briefmg Memo, 04/FB/1998, L. Cheng; and DP# 200157, M.J. Nelson, 17/MAR/1994

The nature of the residue in livestock commodities is adequately understood based on metabolism studies conducted with rimsulfuron, labeled in the pyridine or pyrimidine ring, in field corn, potatoes, tomatoes, lactating goats, and laying hens. The metabolic pathways were found to be similar in plants and livestock. Metabolites detected in livestock in addition to the general metabolites listed in section 4.1.1 are IN-69190 (goat), IN-H1043 (goat) and IN-JF999 (hen). The residue of concern has been determined to be rimsulfuron.

4.1.3	Summary of Confined Rotational Crops (860.l850)
DP# 206712, M. Nelson, 09/02/1994
D418153, M. Negussie, 03/17/2014

Adequate confined rotational crop data are available to support a minimum plant-back interval (PBI) of up to 18 months, depending on the end-use product. As the labels for rimsulfuron currently specifies minimum plant-back intervals compatible with this, data requirements for rotational crops are fulfilled and tolerances are not required for rotational crops. The residue of concern has been determined to be rimsulfuron.

4.2	Comparison of Metabolic Pathways

The major metabolic route of rimsulfuron metabolism/degradation involves sulfonylurea bridge contraction, with sulfonylurea bridge cleavage as a minor metabolic route. The metabolites detected were IN-70941, IN-70942, IN-E9260, IN-J290, IN-69190 (goat), IN-H1043 (goat), IN-T5831 (potato), IN-JF999 (hen, tomato), and unresolved polar/nonpolar products. The metabolism of rimsulfuron has been found to be similar amongst plants and livestock. The expectation is that metabolism will be the same in all plants and animals with minor variations, and that no metabolites of rimsulfuron contributes as a toxic residue in plants, animals or water.

4.3	Residues of Concern Summary and Rationale
D200157 Rimsulfuron Briefing for the HED Metabolism Committee Meeting, 03/23/1994, M. Nelson.
D200158 Rimsulfuron Notes HED Metabolism Committee Meeting, 03/23/1994, M. Nelson.

The metabolic pathways of rimsulfuron have been assessed to be similar in all plants and animals. None of the metabolites of rimsulfuron have been assessed to require inclusion in tolerance regulation, the dietary risk assessment, or additional metabolism or toxicological studies. The residue of concern in all plants and animals is rimsulfuron.

Table 4.3.1.1.  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression
Matrix
Residues included in Risk Assessment
Residues included in Tolerance Expression
Plants
Primary Crop
Rimsulfuron
Rimsulfuron

Rotational Crop

Livestock
Ruminant

Poultry

Drinking Water

Not Applicable

5.0	Residue Profile

5.1	Residue Analytical Methods (860.1340) 

5.1.1	Data Collection Methods
49973401.der, 03/07/2017, R. McGovern
49973402.der, 03/07/2017, R. McGovern

IR-4 utilized modifications to an HPLC/ESI-MS/MS method, DuPont 15033, for determination of residues of rimsulfuron in/on cranberries and seed crop grasses. A method description and validation data were submitted with the field trial data, while an independent laboratory validation (ILV) was not. Briefly, samples were extracted with 0.1M potassium phosphate (pH 7)/methanol (4:1, v/v).  Clean up steps were concluded to be unnecessary and omitted. Extract was centrifuged and a portion of this extract was diluted to 10 mL with 5mM ammonium acetate/methanol (4:1 v/v). This portion was passed through a 0.45 um PTFE filter and analyzed for residues of rimsulfuron using HPLC/ESI-MS/MS. The limit of quantitation (LOQ) is established at 0.01 ppm, and the mass transitions monitored were m/z 432~182 and 432~325.

Validation data included fortified samples of cranberries and grass forage and. Average recoveries and standard deviations in cranberry were 90.6% +- 7.9% over 10 replicates at 0.01 ppm (LOQ), 93.9% +- 2.3% over 6 replicates at 0.1 ppm, and 94.7% +- 0.47% over 3 replicates at 1.0 ppm. Average recoveries and standard deviations in grass forage were 91% +- 11% over 10 replicates at 0.01 ppm (LOQ) and 95% +- 4% over 4 replicates at 0.1 ppm. Average recoveries and standard deviations in grass hay were 89% +- 11% over 10 replicates at 0.01 ppm and 83% +- 7% over 4 replicates at 0.1 ppm.

No radiovalidation data were included in the submission to validate extraction efficiency for the analytical method in cranberry and grass forage and hay matrices. HED concludes that radiovalidation data is not needed due to similarity of extraction solvents used in the enforcement method as compared to the solvents used in the metabolism studies.

Conclusions: An adequate data collection method, HPLC/ESI-MS/MS method DuPont 15033, is available for determination of residues of rimsulfuron in/on cranberry and grass forage and hay commodities. This method is an improvement over the previous method using the same extraction technique, and this method was used to analyze samples from the field trials submitted with this petition. The LOQ was validated in each matrix included in the field trials with 10 replicates of fortified samples. The ILV study requirements are waived in accordance with guideline 860.1340 (ii), and the single-laboratory validation and concurrent recoveries were within the acceptable range (70-120% recovery and >30% RSD). Radiovalidation data are not needed since the extraction solvent for the method is similar to the extraction solvent used in the metabolism studies. 

5.1.2	Multi-Residue Methods (860.1360)
DP# 184551, M. Nelson, 02/25/1994

Rimsulfuron is not recovered by FDA Multiresidue Methods (MRM). The multiresidue method test results have been forwarded to FDA.

Conclusions: The FDA MRM are not appropriate for analysis or enforcement of residues of rimsulfuron.

5.1.3	Tolerance Enforcement Methods
49973401.der, 03/07/2017, R. McGovern
49973402.der, 03/07/2017, R. McGovern

IR-4 has submitted data using a modification to DuPont analytical method 15033. The method is a technological improvement upon the previous method for enforcement of residues of rimsulfuron in/on agricultural commodities using sequential LC/MS systems. Method 15033 has a similar extraction to the previous enforcement method and also to DuPont method 32277, the analytical method used during the last petition for new uses of rimsulfuron.  

Conclusions: An adequate enforcement method, DuPont method 15033 using HPLC/ESI-MS/MS, is available for the enforcement of residues of rimsulfuron on grass seed crops and cranberry commodities. Samples of grass forage and hay and cranberries were analyzed for residues of rimsulfuron using this method and a LOQ of 0.01 ppm for all assessed matrices.

5.1.4	Submittal of Analytical Reference Standards (860.1650)

Sufficient rimsulfuron analytical reference standard is available in the pesticide repository with an expiration date of 03/10/2020 (personal communication with G. Verdin, 03/08/2017).

5.2	Storage Stability (860.1380)
49973401.der, 05/18/2017, R. McGovern
49973402.der, 05/18/2017, R. McGovern

Table 5.2.1.1.  Stability of Rimsulfuron Residues in Cranberries and Grasses Following Storage at -20°C.
Commodity
                                 Spike level 
                                     (ppm)
                               Storage interval
                                     (days)
                              Recovered residues
                                     (ppm)
                            Mean Recovered Residues
                                     (ppm)
                                 Mean Recovery
                                      (%)
                             Corrected % recovery*
                                  Rimsulfuron
Cranberries
                                    0.0997
                                      717
                                    0.05028
                                    0.0491
                                      49
                                      52

                                       
                                       
                                    0.06383
                                       
                                       
                                       

                                       
                                       
                                    0.04720
                                       
                                       
                                       

                                       
                                       
                                    0.04321
                                       
                                       
                                       

                                       
                                       
                                    0.05057
                                       
                                       
                                       

                                       
                                       
                                    0.03970
                                       
                                       
                                       
Grass Forage
                                    0.0997
                                      813
                                    0.07941
                                    0.0802
                                      80
                                      96

                                       
                                       
                                    0.08097
                                       
                                       
                                       

                                       
                                       
                                    0.08032
                                       
                                       
                                       
Grass Hay
                                       
                                       
                                    0.08047
                                    0.0814
                                      82
                                      99

                                       
                                       
                                    0.08359
                                       
                                       
                                       

                                       
                                       
                                    0.08012
                                       
                                       
                                       
* Corrected for mean concurrent recovery

Conclusions: Storage stability data is sufficient to demonstrate the stability of rimsulfuron in grass forage and hay for up to 813 days under frozen (<=-20ºC) conditions. The storage stability data show that rimsulfuron is not stable in cranberries at 717 days or longer under frozen conditions. The data demonstrate that 50% or more of the residue may be lost at 717 days or longer under frozen conditions. Data was not generated for increments less than 717 days frozen, and no conclusion of a maximum storage stability duration in cranberries can be drawn at this time.

5.3	Residue Data

5.3.1	Crop Field Trials (860.1500)
49973401.der, 03/07/2017, R. McGovern
49973402.der, 03/07/2017, R. McGovern

Four crop field trials on grass forage and hay using rye and fescue were conducted with a single application of rimsulfuron in excess of the petitioned for use pattern. The applications were made at ~200 days or greater PHI for forage and ~225 days or greater PHI for hay. No field trial average or individual sample had detectible residues of rimsulfuron above the LOQ (<0.01 ppm). 

Five crop field trials on cranberry were conducted with rimsulfuron applied at the level of the petitioned-for use. The applications were made in accordance with the use directions on the proposed label of minimum 21 days in between each of two applications, 0.0625 lbs ai/A and ~60-day PHI. No field trial average or individual sample had detectible residues of rimsulfuron above the LOQ (<0.01 ppm). The five field trials were conducted in Region 1 (MA), 2 (NJ), 5 (2 trials in WI) and 12 (OR). 

Table 5.3.1.1.  Summary of Residues from Field Trials with Rimsulfuron.
                                 Crop Matrix 
                                    Analyte
                                 Applic. Rate
                                 (lb ai/acre)
                                  PHI (days)
                                     n[*]
                                Residues (ppm)
                                       
                                       
                                       
                                       
                                       
                                   Min.[†]
Max.[†]
                                    LAFT[*]
                                   HAFT[*] 
                                   Median[*]
                                    Mean[*]
                                     SD[*]
Grasses Proposed Use = 0.048 lb ai/acre total application rate, no proposed PHI.
                                    Forage
                                  Rimsulfuron
                                     0.063
                                      197
                                       4
                                   <0.01
<0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      --
                                      Hay
                                       
                                       
                                      224
                                       4
                                   <0.01
<0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      --
Cranberry Proposed Use = 0.0625 lb ai/acre total application rate, 60-day PHI.
                                   Cranberry
                                  Rimsulfuron
                                     0.062
                                      56
                                       5
                                   <0.01
<0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                      --
† Values based on total number of samples.
[*] Values based on per-trial averages.  LAFT = Lowest Average Field Trial, HAFT = Highest Average Field Trial, SD = Standard Deviation.  For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at the LOQ.

Conclusions: All four trials on grasses were conducted in NAFTA Region 12 (Oregon) and satisfy the data requirements for a petition for a regional tolerance on grasses under guideline 860.1500. The field trial data is sufficient to show that finite residues of rimsulfuron are not expected in the mature plants after 200-day PHI and applications up to (and exceeding) the maximum use rate on the proposed label. The storage stability data addressed above in section 5.2 supports the accuracy of this data. Decline data was not generated because all samples contained residues <LOQ, and decline of residues of rimsulfuron in grass forage and hay cannot be assessed at this time.

The NAFTA regional study requirements for establishing a tolerance in cranberry requires the following number and location of studies: Region 1 (2 studies), Region 5 (2 studies) and Region 12 (1 study) for a minimum of 5 studies and 10 discrete treated samples. HED recommends accepting the Region 2 study (NJ) in lieu of a second region 1 study for the purposes of establishing a tolerance with U.S. use of rimsulfuron on cranberries. The data provided from the region 1, 5 and 12 field trial studies indicates that use patterns and results are not significantly different between regions 1 and 2 over the course of the studies. Furthermore, as no individual sample or field trial average resulted in residues above the LOQ, the results from the Region 2 study are effectively identical to the submitted Region 1 study. The storage stability data discussed in section 5.2 indicate that residues of rimsulfuron for all field trials may be approximately 2 times the recovered values. Since all samples results were <LOQ, actual results may range from <LOQ (<0.01 ppm) to 2x LOQ (0.02 ppm). Decline data was not generated because all samples contained residues <LOQ, and decline data of residues of rimsulfuron in cranberry cannot be assessed at this time.

5.3.2	New Uses and Crop Group Conversions

No additional data have been submitted for the following proposed new uses and crop group conversions.

Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F

A tolerance is established for "grape." The petitioner is proposing a new use on the "Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F." The representative crop for subgroup 13-07F is grape. Adequate field trial data are available reflecting use of dry flowable (DF) formulation on grapes (D333256, 5/16/2007, D. Rate et. al.). The data on grapes are adequate to establish a tolerance on the Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F.

Vegetable, tuberous and corm, subgroup 1C

A tolerance is established for "potato." The petitioner is proposing a new use on the "Vegetable, tuberous and corm, subgroup 1C." The representative crop for subgroup 1C is potato. Adequate field trial data are available reflecting use of DF formulation on potato (D184551, 25 February 1994, M.J. Nelson). The data on potato are adequate to establish a tolerance on the Vegetable, tuberous and corm, subgroup 1C.

Fruit, citrus, group 10-10

A tolerance is established on the "Fruit, citrus, group 10." The petitioner is proposing a crop group conversion to the "Fruit, citrus, group 10-10." The representative crops for group 10-10 are orange or tangerine/mandarin, lemon or lime, and grapefruit. Adequate field trial data are available reflecting use of DF formulation on orange, lemon and grapefruit (D333256, 5/16/2007, D. Rate et. al.). The data on orange, lemon, and grapefruit are adequate to establish a tolerance on the Fruit, citrus, group 10-10.

Fruit, pome, group 11-10

A tolerance is established on the "Fruit, pome, group 11." The petitioner is proposing a crop group conversion to the "Fruit, pome, group 11-10." The representative crops for group 11-10 are apple and pear. Adequate field trial data are available reflecting use of DF formulation on apple and pear (D333256, 5/16/2007, D. Rate et. al.). The data on apple and pear are adequate to establish a tolerance on the Fruit, pome, group 11-10.

Fruit, stone, group 12-12

A tolerance is established on the "Fruit, stone, group 12." The petitioner is proposing a crop group conversion to the "Fruit, stone, group 12-12." The representative crops for group 12-12 are sweet cherry or tart cherry, peach, and plum or prune plum. Adequate field trial data are available reflecting the use of DF formulation on sweet cherry, peach and plum (D333256, 5/16/2007, D. Rate et. al.). The data on sweet cherry, peach and plum are adequate to establish a tolerance on the Fruit, stone, group 12-12.

Nut, tree, group 14-12

A tolerance is established on the "Nut, tree, group 14" and "pistachio." The petitioner is proposing a crop group conversion to the "Nut, tree, group 14-12." The representative crops for group 14-12 are almond and pecan. Adequate field trial data are available reflecting use of DF formulation on almond and pecan (D333256, 5/16/2007, D. Rate et. al.). The data on almond and pecan are adequate to establish a tolerance on the Nut, tree, group 14-12.

5.3.3	Field Rotational Crops (860.1900)
DP# 206712, 09/02/1994, M. Nelson

Adequate confined rotational crop data are available to support minimum plant-back intervals up to 18 months, depending on the end-use product. 

Conclusions: As the label for rimsulfuron (Matrix and Pruvin end-use products) currently specifies minimum plantback intervals compatible with these plantback intervals, data requirements for rotational crops are fulfilled and tolerances are not required for rotational crops.

5.3.4	Processed Food and Feed (860.1520)

HED does not require residue data for any processed commodities associated with cranberry or grass forage and hay (seed crops). Previously assessed data is adequate to show that the tolerance of raw agricultural commodities is appropriate to apply to all processed food or feed items derived thereof.

5.3.5	Meat, Milk, Poultry and Eggs (860.1480)
D418153.mem, 03/17/2014, M. Negussie

The grass hay and forage associated with the petitioned use is for seed crop only. As such, there are no ruminant feedstuffs associated with the proposed uses of rimsulfuron on cranberry and grass seed crops. There are ruminant feedstuffs associated with current uses of rimsulfuron, and HED has previously concluded that there is no expectation of finite residues of rimsulfuron in livestock (40CFR §180.6(a)(3)) given current feedstuffs applications and dietary burden calculations.

HED notes that if additional uses of rimsulfuron with livestock feed items are proposed in the future, additional livestock feeding studies may be required.

5.3.6	Food Handling (860.1460)

This guideline requirement is not relevant to the current petition; there are no food handling uses current or proposed for rimsulfuron.

5.3.7	Water, Fish, and Irrigated Crops (860.1400)

This guideline requirement is not relevant to the current petition; there are no aquatic uses current or proposed for rimsulfuorn.

5.4	Food Residue Profile

The proposed use of rimsulfuron on grass seed crops has no expectation of producing finite residues in food. The data support that residues of rimsulfuron are not detectible at harvest of mature crops, and therefore detectible residues of rimsulfuron are not expected in the next generation, should that generation be used as food or feed crops. Previous assessments of rimsulfuron have recommended a plant-back interval (PBI) of up to 18 months for rotational crops.  No decline data could be generated from the crop field studies on grasses because the residues were not detected above the limit of quantitation (LOQ <0.01 ppm). Degradation of rimsulfuron into metabolites in grasses could not be observed but is not expected to impact human health, as all known metabolites have been previously assessed to not be of toxicological concern. No livestock feed uses are associated with the petitioned use on grasses, and rotational crop instructions on the proposed label are considered sufficiently protective of grazing livestock and plant-back of crops for food and feedstuffs.

The available data indicate that finite residues of rimsulfuron on cranberries are not expected to exceed 0.01 ppm (LOQ). No livestock concerns are associated with the proposed use. While some processing may occur on cranberries, HED does not have data requirements associated with processed commodities of cranberry, as such a processing study was not required. HED does not expect significant residues in processed commodities such as cranberry juice due to the extremely low (<LOQ) observed residues of rimsulfuron in cranberry and the demonstrated instability of rimsulfuron in the cranberry matrix, even under frozen conditions. Concurrent recoveries of laboratory fortified cranberry samples showed a loss of more than 50% of rimsulfuron residues under frozen conditions. As with grasses, no metabolites of toxicological concern have been identified or are expected. This petitioned use does not apply to rotational crops. HED concludes that this use will produce negligible residues of rimsulfuron in cranberries and processed cranberry commodities for human consumption. HED further concludes that this food residue profile will remain consistent for all commodities in subgroup 13-07H.

Previous assessments have been conducted for residues of rimsulfuron on the representative crops of groups 10-10, 11-10, 12-12, 14-12, and subgroups 1C and 13-07F. Processing studies have previously been conducted on orange with exaggerated application rate (5x) of rimsulfuron. These studies did not result in recoverable concentrations of rimsulfuron either for the processed or the raw agricultural commodity. As such, concentration from processing could not be assessed for residues of rimsulfuron. The metabolism of rimsulfuron has been assessed in plants and animals to be the same, and HED has previously concluded there is no expectation of finite residues of rimsulfuron in livestock commodities. Data indicate that commodities of subgroup 1C are anticipated to have finite residues of rimsulfuron up to 0.1 ppm. HED assesses that the remainder of commodities in the above groups, and livestock given feedstuffs from these commodities, will not contain detectible residues of rimsulfuron. 

6.0	Tolerance Derivation

For the grass forage and hay samples, residue values were not entered into the OECD calculator because all treated samples bore residues below the LOQ of 0.01 ppm; therefore, 0.01 ppm was selected as the appropriate tolerance for these commodities.

For the cranberry samples representative of subgroup 13-07H, residue values were not entered into the OECD calculator because all treated samples bore residues below the LOQ of 0.01 ppm; concurrent storage stability samples indicate that as much as half of the residue present in the samples may have been lost between the time of harvest and the time of analysis; therefore, 0.02 ppm (twice LOQ) was selected as the appropriate tolerance for subgroup 13-07H.

HED concurs with petitioned conversions of groups 10, 11, 12, and 14 to groups 10-10, 11-10, 12-12, and 14-12, all at the proposed tolerance of 0.01 ppm. No additional data has been provided for these crop group conversions.

HED concurs with the use of the previously established grape tolerance at 0.01 ppm as the representative crop for establishing a tolerance for subgroup 13-07F at 0.01 ppm. Likewise, HED concurs with the use of the previously established potato tolerance at 0.1 ppm as the representative crop for establishing a tolerance for subgroup 1C at 0.1 ppm. No additional data has been provided for these petitioned uses.

Appendix A	Harmonization Considerations for Rimsulfuron

             Harmonization Considerations Summary for Rimsulfuron.
Commodity
Proposed Tolerance 
(ppm)
Current U.S. Tolerance 
(ppm)
Current Canadian MRL
(ppm)
Current Codex MRL (ppm)
Fescue, forage
                                     0.01
                                      --
                                      --
                                      --
Fescue, hay
                                     0.01
                                      --
                                      --
                                      --
Ryegrass, perennial, hay
                                     0.01
                                       
                                      --
                                      --
Ryegrass, perennial, forage
                                     0.01
                                      --
                                      --
                                      --
Berry, low growing, except strawberry, subgroup 13-07H
                                     0.01
                                      --
                           0.05-Lowbush blueberries
                                      --
Fruit, citrus group 10-10
                                     0.01
                   0.01 (currently Fruit, citrus, group 10)
                              0.01-Lingonberries
                                      --
Fruit, pome, group 11-10
                                     0.01
                    0.01 (currently Fruit, pome, group 11)
                                      --
                                      --
Fruit, stone, group 12-12
                                     0.01
                    0.01 (currently Fruit, stone, group 12)
                                      --
                                      --
Nut, tree, group 14-12
                                     0.01
                     0.01 (currently Nut, tree, group 14)
                                      --
                                      --
Vegetables, tuberous and corm, subgroup 1C
                                      0.1
                            0.1 (currently potato)
                                 0.1-Potatoes
                                      --
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                     0.01
                            0.01 (currently grape)
                               0.01-gooseberries
                                      --