### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D

. C

. 20460

OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION

MEMORANDUM

Date: 03/02/2016

Subject: Bensulide. Summary of Analytical Chemistry and Residue Data in Support of Registration Review.

From:

Through:

To: PC Code: 009801 DP Barcode: D429 307

Decision No.: 507866 Registration No .: 10163-200
Petition No .: NA Regulatory Action : Registration Review

Risk Assessment Type : Single Chemical Case No. : 2035

TXR No. : NA CAS No .: 741-58-2

MRID No

. : NA 40 CFR : 180.241

Ideliz Negr6n-Encarnaci6n, Ph.D., Chemist, · RAB V

# ~ "-
Health Effects Division (HED; 7509P)

### ~ 

# 7

Danette Drew

, Senior

## Chemis~D**,** RAB V

## (7509**~**

Thomas Bloem

,

# C~~ Elizabeth Holman, Physical Scientist

### ~**~** ChemSAC Designated Reviewers (HED; 7509P)

Margaret Hathaway I Kevin Costello
Pesticide Re-evaluation Division (7508P)

Summary of Submitted Re s idu e Chemistry Studies
OCSPP 860 MRIDNumber Title
Series
Guideline
860

. 1520 44435501 Magnitude of the Re s idue ofBensulide in Tomato Proce sse d Commodities.

Page 1 of 15Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 2 of 15 Table of Contents

1.0 Executive Summary ............................................................................................................ 3

2.0 Regulatory Recommendations ............................................................................................ 3

2.1 Data Deficiencies/Data Needs .......................................................................................... 3

2.2 Tolerance Considerations ................................................................................................. 4

2.2.1 Enforcement Analytical Method ............................................................................... 4

2.2.2 Recommended Tolerances ........................................................................................ 4

2.2.3 International Harmonization ..................................................................................... 5

3.0 Introduction .................................................................................................................. ....... 5

3.1 Chemical Identity ............................................................................................................. 6

3.2 Physical/Chemical Characteristics ................................................................................... 6

3.3 Pesticide Use Pattern/Direct ions for Use (860.1200) ....................................................... 7

4.0 Metabolite/Degradate Residue Profile ................................................................................ 7

4.1 Nature of the Residue ....................................................................................................... 7

4.2 Residues of Concern Summary and Rationale ................................................................. 8

5.0 Residue Profile ............................................................................................................... ..... 8

5.1 Residue Analytical Methods (860.1340) .......................................................................... 8

5.1.1 Tolerance Enforcement and Data Collection Methods ............................................. 8

5.1.2 Multi-Residue Methods (860.1360) .......................................................................... 8

5.1.4 Submittal of Analytical Reference Standards (860.1650) ........................................ 9

5.2 Storage Stability (860.1380) ............................................................................................ 9

5.3 Residue Data .................................................................................................................. 10

5.3.1 Crop Field Trials (860.1500) .................................................................................. 10

5.3.2 Field Rotational Crops (860.1900) ......................................................................... 11

5.3.3 Processed Food and Feed (860.1520) ..................................................................... 11

5.3.4 Meat, Milk, Poultry and Eggs (860.1480) .............................................................. 12

5.3.5. Food Handling (860.1460) ...................................................................................... 12

5.3.6 Water, Fish, and Irrigated Crops (860.1400) .......................................................... 12

5.4 Food Residue Profile ...................................................................................................... 12
Appendix A. International Residue Limits Table ........................................................................ 14
Appendix B. Comparison of Residue Le vels of Bensulide and its Oxon .................................... 15Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 3 of 15 1.0 Executive Summary

Bensulide [S-(O,O-diisopropyl pho sphorodithioate) ester of N-(2-mercaptoethyl)benzenesulfonamide] is an herbicide registered in th e U.S. for food/feed uses on bulb onion, garlic, shallots, peppers (bell/nonbell), tomatillo, leafy vegetable except brassica (crop group (CG) 4), leafy brassica vegetable (CG 5), and cucurbit vegetable (CG 9), and a regional registration for use on carrots. The registrant as also previously indicated interest in maintaining tolerances in/on tomato for import purposes. Tolerances ra nging from 0.10 to 0.15 ppm are established in the 40 CFR § 180.241 for residues of bensulide in cluding its oxygen analog in/on these raw agricultural commodities. No tolerances have been established for any processed food/feed commodities or any animal commodities. The em ulsifiable concentrate (EC) end-use product Prefar 4-E (EPA Reg. No. 10163-200) is the only be nsulide formulation class registered for use on food/feed crops in the U.S. This formula tion is typically applied to the soil preplant (incorporated) or preeme rgence (banded or broadcas t) using ground equipment.

The residue database for bensulide is complete with the exception of crop field trials with nonbell pepper (domestic) and tomato (import). Adequate methods are available for the enforcement of tolerances for bensulide and its oxygen analog in/on plant commodities. The tolerance expressions in the code of federal regulations (CFR) needs to be modified according to the interim guidance on writing tolerance expressions (S. Knizner, 05/27/2009), and the tolerance for fruiting vegetables CG 8 needs to be removed while a tolerance for tomatillo and bell pepper may be established. A tolerance for tomato may be included pending registrant feedback with regards to data previously requested to support use on imported tomatoes.

2.0 Regulatory Recommendations

There are no residue chemistry considerations that would preclude gr anting reregistration for bensulide on all crops with th e exception of non-bell peppers. The specific label modifications
are discussed in section 2.3.

2.1 Data Deficiencies/Data Needs

Three geographically representati ve field trials on non-bell peppers are required. Pending the submission of these data, the instructions for a pplication to non-bell pe ppers should be removed from the label. This data deficiency was identi fied in the bensulide’s residue chemistry chapter in support of the Registration Eligibility Decision (RED; C. Eiden, D238417, 10/06/1997) and the registration review scoping doc ument (T. Goodlow, D347549, 06/10/2008).

Twelve crop field trials for bensulide on tomato grown in Mexico were re quired in the bensulide residue chemistry chapter in support of the Re gistration Eligibility Decision (RED; C. Eiden, D238417, 10/06/1997). The label fro m Mexico was submitted and describes a similar use pattern with the one registered in the US. Th e registrant expressed their intent to submit a proposal to address this data gap (confere nce call on 11/16/2015, coordinated by Margaret Hathaway). Pending the submission of these data, th e twelve crop field trials are still required.Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 4 of 15 2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate methods are available for tolerance enforcement for plant commodities. The Pesticide Analytical Manual (PAM) Vol. II lists Gas Ch romatography (GC) Method I, using either phosphorus-sensitive thermionic de tection or flame photometric detection, for the determination of bensulide and bensulide oxygen analog in pl ant commodities. Thin layer chromatography (TLC) Method A is available for confirmation. Moreover, the PAM (Volume I, Appendix I) indicates that bensulide is recovered using Mu ltiresidue Methods Sections 302 (Luke Method; Protocol D), 304 (Mills Method; Protocol E, fatty foods) and 303 (Mills, Onley, Gaither Method; Protocol E, non-fatty foods). No information re garding the recovery of bensulide oxygen analog using Multiresidue Methods is in cluded in the PESTDATA database.

2.2.2 Recommended Tolerances

HED recommends modifying the tolerance expr ession and crop groups in cluded in the CFR for bensulide. The tolerance expres sions in the 40 CFR § 180.241 (a) and (c) need to be modified to include both, coverage and comp liance statements for enforcement purposes, as recommended in the Interim Guidance on Writing Tolerance Expressions (S. Knizner, 05/27/2009). The recommended tolerance expressions are:

(a) General. “Tolerances are established for residues of the herbicide bens ulide, including its metabolites and degradates, in or on the commoditi es in the following table. Compliance with the tolerance levels specified in the table below is to be determined by measuring only bensulide, S- (O,O-diisopropyl phosphorod ithioate) ester of N-(2-mercaptoet hyl) benzenesulfonamide, and its oxygen analog, S-(O,O-diisopropyl phosphorot hioate) of N-(2-mercaptoethyl) benzenesulfonamide, in or on the commodity.”

(c) Tolerance with regional registration. “Tolerances with regional registration, as defined in §180.1(l), are established for residue s of the herbicide bensulide, including its metabolites and degradates, in or on the commodities in the followi ng table. Compliance with the tolerance levels specified in the table below is to be determin ed by measuring only bensulide, S-(O,O-diisopropyl phosphorodithioate) ester of N-(2-mercaptoethyl ) benzenesulfonamide, and its oxygen analog, S- (O,O-diisopropyl phosphorothioate ) of N-(2-mercaptoethyl) benzenesulfonamide, in or on the commodity.”

Since non-bell pepper field trial data are not avai lable, HED concludes that the fruiting vegetable crop group 8 tolerance should be deleted and bell pepper and tomatillo tolerances established in support of domestic registrations. Additional data is required to support a tolerance for tomato imported from Mexico. The estab lishment of a tolerance for tomato may be recommended if this data (or a waiver request) is received from the re gistrant and considered adequate to support this
use. Tolerances included in the 40 CFR 180.241 need to be modified as specified in the table
below.Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 5 of 15 Table 2.2.2. Tolerance Summary for Bensulide. Commodity Established Tolerance (ppm) HED-Recommended Tolerance (ppm) Comments ( correct commodity definition ) Vegetable, fruiting, group 8 0.10 Remove Pepper, bell None 0.10
Tomatillo None 0.10 Tomato, subgroup 8-10A* None 0.10 *May be established pending review of required data in support of import use.

2.2.3 International Harmonization

There is no Codex, Mexican or Canadian maximum residue limits established for bensulide. Therefore, harmonization is not germane to this assessment.

2.3 Label Recommendations

The following recommendations are based on the re view of the label of bensulide’s end use product Prefar 4-E (EPA Reg. No. 10163-200, 12/13/2013):

 The current label of Prefar 4-E includes inst ructions for use on non-bell peppers such as chili peppers, cooking peppers, pimentos and sweet peppers. A magnitude of residue study for bensulide in/on non-bell peppers ha s been required in the RED and scoping document. Alternatively, it was indicated that the registrant could restrict use to bell peppers. Since these data have not been received, HED reco mmends that the label of the bensulide products containing instructions for use on bell and non-bell peppers is modified to restrict the use to only bell pe ppers. Moreover, reference to the fruiting vegetables crop group needs to be removed.

 The maximum seasonal application rate for cucurbit vegetables, tomatillo and bell peppers needs to be specified in the label of Prefar 4-E. A maximum seasonal application rate of 6 lbs ai/A is adequate for crops under these crop groups.

3.0 Introduction

Bensulide [S-(O,O-diisopropyl pho sphorodithioate) ester of N-(2-mercaptoethyl)benzenesulfonamide] is a herbicide registered for food/ feed uses on brassica leafy vegetables, carrots, peppers (bell/nonbell), tomatillo, cucu rbits, leafy vegetables, and bulb onions. Bensulide’s mode of action is through the inhibiti on of cell division in the root s and shoots of plants. The emulsifiable concentrate (EC) e nd-use product is the only bensulid e formulation class registered for use on food/feed crops. These formulations are typically applied to the soil preplant (incorporated) or preeme rgence (banded or broadcas t) using ground equipment.Bensulide Summary of Anal ytical Chemistry and Residue Data Barcode D429307

Page 6 of 15 3.1 Chemical Identity

Table 3.1. Bensulide and Bensulide Oxon Nomenclature. Compound Chemical Structure

Common name Bensulide

IUPAC name O,O-diisopropyl-S-2-phenylsulfonylaminoethylphosphorodithioate

CAS name S-(O,O-diisopropyl phosphorodithioate) ester of N-(2-mercaptoethyl)
benzenesulfonamide
CAS # 741-58-2 Compound Chemical Structure

Common name Bensulide Oxon

IUPAC name O,O-diisopropyl-S-2-phenylsulfonylaminoethylphosphorothioate

CAS name S-(O,O-diisopropyl phosphorothioate) of N-(2-mercaptoethyl)
benzenesulfonamide

CAS # 20243-81-6

3.2 Physical/Chemical Characteristics

Bensulide (5.6 mg/L) is moderately soluble in water; however, it is less soluble than its oxon (461 mg/L, EPISuite v. 4.10). Both compounds have low volatility and the oxon has a lower octanol/water partition coefficient.

Table 3.2. Physicochemical Properti es of Bensulide and Bensulide Oxon
Parameter Value Reference

Bensulide Molecular weight (g/mole) 397.54 MRID 45761801 Melting point (°C) 36 MRID 41532001 Water solubility ( mg/L at 25°C) 5.6 MRID 41532001 Vapor pressure at 25°C (mmHg) 8.2 x 10 -7 MRID 41532001 Dissociation constant (pK
a ) Not Applicable Octanol/water partition coefficient Log(K OW ) 4.20 H. Zhong, D428601, 09/14/2015 (values modeled with EPI Suite, v 4.10)

Bensulide oxon Molecular weight (g/mole) 381.44 H. Zhong, D428601, 09/14/2015 (values modeled with EPI Suite, v Melting point (°C) 89.97 Water solubility ( mg/L at 25°C) 461.24Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 7 of 15 Table 3.2. Physicochemical Properti es of Bensulide and Bensulide Oxon
Parameter Value Reference Vapor pressure at 25°C (mmHg) 2.48 10 -8 4.10)
Dissociation constant (pKa) Not Applicable Octanol/water partition coefficient Log(K O W ) 2.35

3.3 Pesticide Use Pattern/Directions for Use (860.1200)

Prefar 4 E (EPA Reg. No. 10163-200) is the only be nsulide end-use produc t registered in the U.S. for food uses; it is registered for app lication to bulb onion, ga rlic, shallots, peppers (bell/nonbell), tomatillo, leafy ve getable except brassica (CG 4), leafy brassica vegetables (CG 5), cucurbit vegetables (CG 9), and regional us e on carrots grown in Texas. Maximum single application rates range fro m 5 to 6 lbs ai/A.

Conclusions: Since magnitude of the residue data have not been submitted for non-bell peppers, HED concludes that they should be removed from the label. For clarity, the label needs to be modified to remove reference to the fruiting ve getable crop group and specify application to bell peppers and tomatillo. In addition, the maximum s easonal application rate is not specified for cucurbit vegetables, tomatillo, or bell peppers. A maximum seasonal appl ication rate of 6 lbs ai/A is adequate for cr ops in these crop groups.

4.0 Metabolite/Degradate Residue Profile Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

4.1 Nature of the Residue

Plants: The reregistration requirements for plant metabolism are fulfilled. Acceptable studies depicting the qualitative nature of the residue in carrots, lettuce, and tomatoes have been
submitted and evaluated. HED has determined that the bensulide residues of concern are those that are currently regulated, bens ulide and bensulide oxygen analog.

Livestock: Data pertaining to the na ture of the residue in anim als are not required. The only livestock feed item associated with registered bens ulide uses is carrot culls which is fed to dairy cattle and may consist of up to 10% of the diet. Currently, product labels include a restriction against the feeding of treate d carrots to livestock. Alt hough the Agency normally does not support this type of feeding restriction, in the 1997 chemistry chapter for the RED it was
determined that this restriction can be allowed be cause use of bensulide on carrots is limited to TX and low residues are present on carrots. If ad ditional uses of bensulide that may result in residues in feedstuff are proposed in the future, livestock metabolism studies will be required.

Confined Rotational Crops: The reregistration requirements for accumulation in rotational crops are fulfilled. An adequate confined rotational crop study has been submitted and
evaluated. The nature of the residue in rotational crops appeared to be similar to the nature of the residue in primary crops. No limited field tr ials or tolerances for inadvertent residues of bensulide were required, provided that a 120-day plantback interval is established for rotationalBensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 8 of 15 crops. Limited field rotational cr op trials would be required to s upport plantback intervals of less than 120 days. Currently, product labels specify a plantback interval of 120 days for all crops
not included on the label.

4.2 Residues of Concern Summary and Rationale

The nature of the residues in plants is adequate ly established based on ca rrot, lettuce and tomato
metabolism studies. The residues of concern for risk assessment in plants and drinking water and tolerance enforcement in plants consists of bensulide and its oxon (C. Eiden, D238417, 10/06/1997).

Table 4.3. Summary of Metabolites and Degradat es to be included in the Risk Assessment and Tolerance Expression

Matrix Residues included in Risk
Assessment Residues included in Tolerance Expression

Plants Primary Crop Bensulide and its Oxon Bensulide and its Oxon

Rotational Crop NS 1 NS 1

Livestock Ruminant NR 1 NR 1 Poultry

Drinking Water Bensulide and its Oxon Not Applicable

1 NS = Not specified. It was indicated that the nature of th e residue seems to be similar to that on primary crops (C. Eiden, D218575, 04/02/1997). Following the 120-day plant-back interval (PBI), residues in rotational crops do not
need to be considered for risk asse ssment and tolerance enforcement.

2 NR = Not required to support the established uses of bensulide. Livestock metabolism studies may be required if new uses are sought.

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1.1 Tolerance Enforcement and Data Collection Methods Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

Adequate methods are available for data co llection and tolerance enforcement for plant
commodities. The PAM Vol. II lists GC Method I, using either phosphorus-sensitive thermionic detection or flame photometric detection, for th e determination of bensulide and bensulide oxygen analog in plant commodities. Moreover, TLC Method A is available for confirmation.
Method I uses benzene as a solvent. Methods us ed for data collection were modifications of
Method I with the substitution of toluene for benzene.

5.1.2 Multi-Residue Methods (860.1360) Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

The PAM (Volume I, Appendix I) i ndicates that bensulide is comp letely recovered (>80%) using Multiresidue Methods Sections 302 (Luke Method; Protocol D) and 304 (M ills Method; ProtocolBensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 9 of 15 E, fatty foods) and partially recovered (70%) using Section 303 (Mills, Onley, Gaither Method; Protocol E, non-fatty foods). No information re garding the recovery of bensulide oxygen analog using Multiresidue Methods is in cluded in the PESTDATA database.

5.1.3 Data Acquisition Methods Tomato Processing Study: 4435501.der.doc

The samples used in the tomato processing st udy were analyzed for bensulide and bensulide oxon by EN-CAS Analytical Laboratories using the analytical method #CSJ-009-02, entitled Analytical Method for the Determination of Be nsulide and Bensulide Oxon in Various Crops by Gas Chromatography, issued 6/01/94, included in Gowan Study #94005-GOWN, RAC Residues - Bell Peppers as the reference method with minor EN-CAS modifications as needed. The method was validated for analysis of whol e tomatoes. Method validation recoveries for bensulide ranged from 88 to 92% (mean= 90% ± 1.5, n = 6). Method vali dation recoveries for bensulide oxon ranged from 86 to I 06% (mean= 96% ± 7.6, n = 6). One unfortified control and two control samples fortified at different levels of bensulid e and bensulide oxon and duplicate subsamples of the two samples from the treated plot were analyzed for each set. Bensulide procedural recoveries ranged from 94 to 101% (mean= 97% ± 3.0, n = 4). Bensulide oxon procedural recoveries ranged from 76 to 81% (mean= 78% ± 2.4, n = 4).

Conclusions: An adequate data acquisition method was used to analyze the samples of bensulide on tomato. The method is supported by adequate method validation and concurrent recoveries for bensulide and its oxygen analog.

5.1.4 Submittal of Analytical Reference Standards (860.1650)

Reference standards for bensu lide (expiration date 04/30/2018) and its ox ygen analog (expiration date 07/23/2017) are currently av ailable in the standa rd repository (personal communication with Gregory Verdin, 09/29/2015). Thes e standards need to be supplie d before their expiration date.

5.2 Storage Stability (860.1380) Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

A storage stability study evaluated in the RED indi cated some degree of instability of residues of
bensulide per se in/on broccoli, cabbage, cucumber a nd leaf lettuce under frozen storage
conditions. Residues of bensulide per se were demonstrated to be st able for up to 6 months in/on cabbage and cucumber, and for less than 3 months in/on broccoli and leaf lettuce. Residues of
bensulide per se declined by 55-61% in/on broccoli after 12 m onths and by 51-53% in cabbage, 43-46% in/on cucumber, and 57-59% in/on leaf lettuce after 36 months. Based on the storage intervals employed in the submitted residue st udies and the stability data submitted, HED
believes that residues of bensu lide oxon were stable during the given storage periods prior to analysis.

The Agency considered the results of the ava ilable storage stability data during tolerance reassessment, and concluded that in order to account for potentia l residue losses during storage prior to analysis, the tolerance for bensulide residues should be increased from 0.10 ppm (based
on non-detectable leve ls of bensulide per se (0.05 ppm) plus bensulide oxon (0.05 ppm)) to 0.15Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 10 of 15 ppm (based on twice the limit of detection for bensulide per se (0.10 ppm) plus the limit of detection for bensulide oxon (0.05 ppm)) for the following commodities or crop groups: curcurbits, leafy vegetables, Bras sica (Cole) leafy vegetables group. Residues of bensulide and
bensulide oxon were stable in ca rrots (data translated from potat oes), onions, and bell peppers during the periods of storage prio r to analysis. Therefore, tolerances for these commodities are
based on field trial data that has not been co rrected for residue losses during storage.

For the tomato processing study, frozen samples were received at EN-CAS from the field test sites on 8/20/97. Samples were transferred to a laboratory freezer for storage where they remained frozen until homogenization and s ubsampling. Freezer storage temperatures were monitored on a daily basis and were maintained approximately at or below 14 ° F. Complete temperature monitoring data are available upon re quest. Sample storage time from sampling in the field to extraction for analysis at the analytical la boratory was 8 days.

Conclusions. Adequate storage stability data are avai lable to support the established uses of
bensulide. The established tole rances have been modified to consider potential loss that may have occurred during storage of the field trial sa mples. Because the storage time from sampling of the tomato samples in the field to analysis was 8 days, the samples of the processing study are supported by adequate st orage stability data.

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500) Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

Adequate data are available to support the currently registered uses on bulb onion (garlic and shallot), tomatillo, bell-peppers, leafy vegetable except brassica (C G 4), leafy brassica vegetable (CG 5), and cucurbit vegetable (CG 9), and carrots grown in Texas.

Non-bell Peppers

Representative commodities for the fruiting vege tables crop group 8 include tomato, bell pepper, and a cultivar of a non-bell pepper. A magnitude of residue study for be nsulide in/on non-bell peppers has been required in the RED a nd scoping document. Three geographically representative field trials on non-bell peppers were required. These data have not been submitted. Alternatively, it was indicated that the registra nt could restrict use to bell peppers only. Currently, the bensulide end- use product label (e.g. Prefar 4-E; EPA Reg. No. 10163-200, 12/13/2013) includes instructions for use on non- bell peppers such as chili peppers, cooking peppers, pimentos and sweet peppers. In the ab sence of the required non -bell pepper data, the
label should be amended to remove the non-bell pepper cultivars and restrict the use to bell peppers only.

Tomato

The established domestic use on tomatillo is c overed by the tolerance for tomato (40 CFR § 180.1). Therefore, the tomato domestic field tria l data does support the tomatillo use. In the residue chemistry chapter for the RED it was stated that the registrant had previously proposed toBensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 11 of 15 retain the tolerance for fruiting vegetables crop group 8 (i.e. includes tomato) for import purposes. To support the import tolerance, HED re quested English translations of the labels from all countries where bensulide can be applied to tomato, 12 tomato field trials conducted in Mexico, and a tomato processing study. The Me xican labels were provi ded by the registrant (Prefar 480-E, Mexican label received on 11/16/2 015) and a tomato processing study is available (MRID 44435501, currently under review). Crop field trial data conducted in Mexico has not been submitted. However, the Mexican label specifies a single application rate of 6 lbs ai/A to
tomato. HED notes that domestic tomato field trial data are available which employed a single preplant incorporated or preemergence broadcast application of the 4 lb/g al EC formulation at 4.0 lb ai/A (8 trials), 5.0 lb ai/A (5 trials), 6.0 lb ai/A (5 trials), 8.0 lb ai/A (1 trial), or 10 lb ai/A (1 trial) followed by harvest of tomatoes at matur ity in 15 trials, green tomatoes in 4 trials in CA (5 lbs ai/A), and the en tire tomato plant in 1 trial (overall, PHIs ranged from 65 to 165 days); residues of bensulide and its oxygen analog we re less than the LOQ (<0.05 ppm each) in/on samples (C. Eiden, D238521, 10/07/1997). The regist rant indicated their intent to submit a proposal or waiver for the previously reque sted crop field trials (11/30/2015, meeting coordinated by Margaret Hathaway). Provided that the US crop field trials were conducted in
locations with similar climate and conditions to t hose in Mexico, and that the final review of the label indicates that the application scenarios in the US and Mexico are similar, HED may
conclude that these field trial data are sufficient to waive the previously requested 12 Mexican tomato field trials and support a tolerance of 0.10 ppm in/on impor ted tomato. Otherwise, the petitioner should submit the previous ly requested 12 Mexican tomato field trials conducted at the maximum rate for the importing countries.

Conclusion: Magnitude of residue studies are required to support uses on non-bell peppers. In the absence of this study it is recommended that this use is eliminated from the label. Crop field trial data (or an acceptable waiver request) needs to be submitted to establish a tolerance for tomato imported from Mexico.

5.3.2 Field Rotational Crops (860.1900) Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

Based on the confined rotational study, no limited field trials or tolerances for inadvertent residues of bensulide were require d, provided that a 120-day plantback interval is established for rotational crops. Limited field rotational crop trials would be require d to support plantback intervals of less than 120 days. Currently, product label specify a plantback interval of 120 days for all crops not included on the label.

5.3.3 Processed Food and Feed (860.1520) Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997 Tomato Processing Study: 44435501.der.doc

Tomato processing studies were required in the RED to support domestic uses or residues in/on imported tomatoes. Currently, the only crop under the tomato subgroup that is registered for domestic uses is tomatillo which is used mainly as seasoning, in chili sauce, salsas, and meats. Moreover, a tomato processing study was required to support uses on tomato to be imported.

A tomato processing study was provided by th e registrant (MRID 44435501). This study wasBensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 12 of 15 conducted in tomatoes following one ground applic ation with Prefar® He rbicide whose active ingredient is bensulide. A field trial was established at in California. Since tomatoes grown in California represent greater th an 68% of the U.S. production, testing in this area ensured adequate representation. Two plot s were established at the test site. One plot was untreated and provided control samples. Another plot was treate d with an exaggerated a pplication rate of the test substance. Bensulide was applied to the trea ted plot one time as a preplant incorporated application. The application was ma de at an exaggerated rate (5 X) of 29.8 lb active ingredient (a.i.)/A in 29 gallons per acre (GPA) of carri er using a tractor-mounted ground sprayer. Whole
fruit was collected at normal commercial matu rity 99 days after the application (DAA) and shipped frozen overnight with dry ice to the anal ytical laboratory. These samples were analyzed immediately. Since residues in the RAC samples were <0.1 ppm, processing of the tomatoes was not required.

Conclusions: Tolerances for tomato processed comm odities are not required since the tolerance for the RAC covers residues in processed commodities.

5.3.4 Meat, Milk, Poultry and Eggs (860.1480) Residue Chemistry Chapter for the RED: C. Eiden, D238417, 10/06/1997

Feeding studies for bensulide in/on livestock ar e not required. The onl y livestock feed item associated with registered bensulide uses is carrot culls which is fed to dairy cattle and may consist of up to 10% of the diet. Currently, product labels include a restriction against the feeding of treated carrots to livestock. In the 1997 chemistry chapter for the RED it was
determined that this restriction can be allowed be cause use of bensulide on carrots is limited to Texas and low residues are present on carrots. If additional uses of bensulide are required in the future, livestock feeding studies may be required.

5.3.5. Food Handling (860.1460)

Bensulide is presently not registered for use in food-handling establis hments; therefore, no residue chemistry data are requi red under this guideline topic.

5.3.6 Water, Fish, and Irrigated Crops (860.1400)

Bensulide is presently not registered for dire ct use on water and aquatic food and feed crops; therefore, no residue chemistry data are required under this guideline topic.

5.4 Food Residue Profile

The nature of the residues in plants is adequate ly established based on ca rrot, lettuce and tomato
metabolism studies. Tolerances are establishe d in the 40 CFR § 180.241 for the use of bensulide on bulb onion, leafy vegetable excep t brassica (CG 4), leafy brassi ca vegetables (CG 5), fruiting vegetable (CG 8), and cucurbit vegetables (CG 9) , and a regional registration for use on carrots. Uses on garlic and shallots are in the label as well which is covered by the tolerance for bulb onion, refer to the 40 CFR § 180.1. The establishe d tolerances are based on measurement of bensulide and its oxygen analog and range from 0.10 to 0.15 ppm. The 0.10 ppm tolerances are based on combined levels of bensulide and its oxon at the LOQ of 0.05 ppm. However, in orderBensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 13 of 15 to account for potential residue loss es during storage prior to analys is, the tolerance for bensulide residues on brassica vegetables (C G 5), cucurbit vegetables (CG 9) and leafy vegetables (CG 4) is 0.15 ppm (based on twice the lim it of quantitation for bensulide per se (0.10 ppm) plus the limit of quantification for bensulide oxon (0.05 ppm)).

Metabolism studies conducted with lettuce, carrot a nd tomato show that parent bensulide was at quantifiable levels only in carrot, while the oxyg en analog was quantified in lettuce and carrot, refer to Appendix B. Levels of the oxon were higher than those of parent bensulide only in lettuce, which suggest that the oxon may predomin ate. Moreover, PDP data for lettuce (years 2010 and 2011) shows that bensulide was detected in 6 of 1487 samples whereas bensulide oxon was detected in 49 of those 1487 samples. Gene rally, the concentration of the oxon in/on lettuce is higher than that of parent bensulide. PDP da ta for carrots do not show quantifiable residues of
bensulide or its oxon while data for tomato do not shows residues of bensulide’s oxygen analog.Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 14 of 15 Appendix A. International Residue Limits Table



### Bensulide (PC Code 009801)

Summary of U.S. and International Tole rances and Maximum Residue Limits Residue Definition : U.S. Canada Mexico 2 Codex
40 CFR 180.241: (a) General. (1) -(O,O-diisopropyl phosphorodithioate) of N-(2-mercaptoethyl) benzenesulfonamide including its oxygen analog S-(O,O-diisopropyl phosphorothioate) of N-(2- mercaptoethyl) benzenesulfonamide None None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

U.S. Canada Mexico 2 Codex
Onion, bulb 0.10 Vegetable, brassica, leafy group 5 0.15 Vegetable, cucurbits group 9 0.15 Vegetable, fruiting group 8 0.10 Vegetable, leafy except brassica group 4 0.15

Completed: M. Negussie; 09/21/15

1 Includes only commodities of interest for this action.

2 Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes.

(c) Tolerances with regional regi strations. Tolerances with regional re gistration, as defined in §180.1(l), are established for the residues of S-(O,O-diisoprop yl phosphorodithioate) of N-(2-mercaptoethyl) benzenesulfonamide including its oxygen analog S- (O,O-diisopropyl phosphorothioate) of N-(2- mercaptoethyl) benzenesulfonamide in or on the following food commodities:

Commodity Parts per million

Carrot, roots 0.10Bensulide Summary of Analytical Chemistry and Residue Data Barcode D429307

Page 15 of 15 Appendix B. Comparison of Residue Levels of Bensulide and its Oxon

Table B.1 summarizes residue data for commodities that do not have PDP data available for both parent bensulide and its oxon. The purpose is to provide information to address the dietary exposure and risk assessment. In addition, PDP data for lettuce (in which bensulide and its oxon were measured) were included.

Table B.1. Summary of Residue Levels for Bensulide and its Oxon

Matrix (Reference) Use Pattern / PDP Sample ID Bensulide Bensulide
Oxon Factor (Oxon/Parent)
Tomato Metabolism (D179576, 04/21/1993) 8.6 lbs ai/A pre-plant 112-153 day PHI ND (86% TRR iden/char) ND (86% TRR iden/char) NA

Lettuce Metabolism (D1855889, 03/29/1993) 8.6 lbs ai/A soil preplant 67 day PHI ND (86% TRR extracted) 2% TRR (86% TRR extracted) NA

Carrot Metabolism (D177460, 06/02/1992) 8.6 lbs ai/A soil preplant 126 day PHI 30% TRR (94% TRR extracted) 2.8% TRR (94% TRR extracted) 0.09x

Squash Field Data (D218256, 01/24/1996) 9 lbs ai/A pre-plant ND 1 ND 1 NA

Cucumber Field Data (D218256, 01/24/1996) 9 lbs ai/A pre-plant ND 1 ND 1 NA

Bulb Onion (D206633, 11/29/1994) 9 lbs a.i./A pre-plant or

pre-emergence Harvest at Maturity ND 1 ND 1 NA

Bell Peppers (D238521, 10/07/1997) 5-9 lbs ai/A pre-plant or

pre-emergence 109-129 day PHIs ND 1 ND 1 NA

Lettuce PDP Results (years 2010-2011) 2010-6721 0.005 0.01 2.0
2010-6845 0.004 0.005 1.3
2010-7044 0.014 0.12 8.6
2010-7052 0.005 0.008 1.6
2010-7265 0.014 0.023 1.6
2011-6295 0.012 0.003 0.3

1 The LOQ is reported to be 0.05 ppm.

Lettuce : The metabolism study with lettuce showed detection of the oxon but not of the parent bensulide which suggest that the oxon may pre dominate. PDP data for lettuce (years 2010 and 2011) shows that bensulide (LOD ≤ 0.014 ppm) was detected in 6 of 1487 samples whereas bensulide oxon (LOD ≤ 0.002 ppm) was detected in 49 of those 1487 samples. The samples in
which both were detected were included in the ta ble above in order to estimate the ratio of the concentration of the oxon with respect to parent bensulide. These factors range from 0.3 to 8.6. This data suggest a factor of 9x for oxon residues with respect to bensulide.

Other Crops (Non-Leafy): The metabolism study with tomato and carrot and the crop field trial data do not suggest that parent bensulide or the oxon may be present at significant concentrations. PDP data with summer squash, carrot and tomato was generated for bensulide and its oxon. Only two sample of tomato showed bensulide being detect ed; however, there were not detects of the oxon. This suggest that both residues of concern would be at low concentrations and that the oxon do not seem to predominate in these crops.Bensulide [PC Code 00980 I ] / Gowan Company

B.7.7

B.7.7.1

B.7.7.2

B.7.7.3

B.7.7.3.1

Document ID: Report:

Guidelines: Effects of Industrial Processing and/or Household Preparation (Annex HA 6.5; Annex IHA 8.5)

Nature of the Residue (Annex HA 6.5.1; Annex IHA 8.5.1) -Not a data requirement in North America

Distribution of the Residue in Peel/Pulp (Annex HA 6.5.2; Annex IHA 8.5.2)

To be included if available.

Magnitude of Residues on Set of Representative Processes (Annex HA 6.5.3; Annex IHA 8.5.3)

Tomato

MRID No. 44435501 Carringer, S. (1997) Magnitude of the Residue of Bensulide in Tomato
Processed Commodities. Study Numbers: AA970609 and 97-0003. Unpublished study prepared by Gowan Company. 162 p. EPA OCSPP Harmonized Test Guideline 860.1520 Processed Food/Feed (August 1996)

PMRA Regulatory Directive DIR98-02 -Residue Chemistry Guidelines,
Section 10

- Processed Food/Feed
OECD Guideline 508 Magnitude of the Pesticide Residues in Processed
Commodities (October 2008)
GLP Compliance: No deviations from regulatory requirements were reported which would
have an impact on the validity of the study. Acceptability: The study is considered scientifically acceptable. The acceptability of this study for regulatory purposes is addressed in the forthcoming U.S. EPA
Residue Chemistry Summary Document,**DP#~.,?·** Evaluator: Ideliz Negr6n-Encamaci6n, Ph.D., Chemist**~---**

Note: This Data Evaluation Record (DER) was originally prepared under contract by Versar

, Inc

. (6850 Versar Center

, Springfield, VA 22151 ; submitted 12 / 04 / 2015). The DER has been reviewed by HED and revised to reflect current Office of
Pesticide Programs (OPP) policies.

EXECUTIVE SUMMARY

In response to the Residue Chemistry Chapter of the Bensulide Reregistration Eligibility
Decision (RED; DP# 238417, C. Eiden, 9/11/97), Gowan Company has submitted a processing study with bensulide on tomato. In one trial conducted in CA during the 1997 growing season, a 4 lb ai/gal emulsifiable concentrate (EC) formulation of bensulide (Prefar® Herbicide) was applied to tomatoes as a single preplant incorporated application at 29.8 lb ai/A (designated 5x by the petitioner) the day before planting. The application was made using ground equipment in

a spray volume of29 gal/A. No adjuvant was used. Tomatoes (RAC) were harvested at

EPA MRID #: 44435501 Page I of5Bensulide [PC Code 009801]/Gowan Company

EPA MRID #: 44435501 Page 2 of 5 maturity 98 days after planting ( DAP) at a 99-day preharvest inte rval (PHI). No processing was conducted with the study.

Samples were stored frozen at the test facility, during shipping, and at the analytical laboratory until analysis. The storage interval between harvest and analysis was 8 days. Samples were analyzed on the day of extraction. No storage stability data are needed to support the study.

Samples were analyzed for residues of bensulide and bensulide oxon using a gas chromatography method with flame photomet ric detection (GC/FPD), Method #CSI-009-02, with minor modifications. Acceptable method validation and concurrent recoveries were reported for samples of tomato fortified with bensulide and bensulide oxon each at 0.05-5.0 ppm, thus validating the method. The limit of quantita tion (LOQ; determined as the lowest level of method validation, LLMV) was 0.05 ppm for each anal yte. The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels. Concurrent
recoveries were corrected for a pparent residues in controls; resi dues in treated samples were not
corrected for residue s in controls.

Following a single preplant incorpor ated application of a 4 lb ai/g al EC formulation of bensulide at an exaggerated rate of 29.8 lb ai/A, residues of bensulide an d bensulide oxon were each below the LOQ (<0.05 ppm) in/on all samples of tomat o. Because residues were below the LOQ in/on all samples following exaggera ted-rate (reportedly ~5x) application, no processing was
conducted.

The maximum theoretical processing factors fo r tomato are 1.4x and 5.5x for puree and paste (based on loss of water; OCSPP 860.1520, Table 2) and 1.4x for juice (based on separation into components; OCSPP 860.1520, Table 3).

I. MATERIALS AND METHODS

A. MATERIALS

Table B.7.7.3.1-1. No menclature for Bensulide.

Common name Bensulide Identity S-(O,O-diisopropyl phosphorodith ioate) ester of N-(2- mercaptoethyl)benzenesulfonamide

CAS no. 741-58-2 Company experimental name Not applicable Other synonyms (if applicable) Not Applicable

Common name Bensulide oxon Identity S-(O,O-diisopropyl phosphorot hioate) ester of N-(2- mercaptoethyl)benzenesulfonamide

CAS no. 20243-81-6 Company experimental name Not applicable Other synonyms (if applicable) Bensulide oxygen analogBensulide [PC Code 009801]/Gowan Company

EPA MRID #: 44435501 Page 3 of 5 Table B.7.7.3.1-1. No menclature for Bensulide.

B. Study Design

1. Test Procedure

One trial was conducted on tomato in CA during the 1997 growing season reflecting a single preplant incorporated application of a 4 lb ai/gal EC formulation of bensulide at an exaggerated

rate.

Location and detailed use pattern for th e trial is provided in Table B.7.7.3.1-2.

Table B.7.7.3.1-2. Study Use Pattern.
Location: City, State;
Year (Trial ID) End-use
Product 1 Method of Application/ Timing of Application Volume (gal/A) Rate per Application

(lb ai/A) Retreatment Interval (days) Total
Rate (lb ai/A) Surfactant/ Adjuvant

Porterville, CA; 1997 (AA970609.CA) 4 lb ai/gal
EC 1. Preplant incorporated; 1 day before planting. 29.6 29.8 -- 29.8 None

1 4 lb ai/gal emulsifiable concentrate (EC) formulation (Prefar® Herbicide).

The registrant indicated that tomatoes were init ially stunted, presumably due to the exaggerated rate of the test substance app lication; however, tomatoes had r ecovered by harvest and were in excellent condition. Irrigation was used as ne cessary. No unusual weather conditions were reported to have adversely affected cr op production or yield during the study.

Sample Handling and Preparation

Single control and duplicate treated samples (>5.0 lb) of tomatoes were collected 98 DAP at a PHI of 99 days. Samples were placed in frozen st orage (-7 to 16 °F) at the test site within 1 hour of collection and were shipped frozen within 5 da ys of harvest via overnight delivery on dry ice to the analytical laboratory, EN -CAS Analytical Laboratories (W inston-Salem, NC). Samples were stored frozen ( ≤ 14 °F) at the analytical laboratory un til analysis. Samples were prepared for analysis by homogenizing in the presence of dry ice.

Sample Processing

No processing was conducted.

2. Description of Analytical Procedures

Samples were analyzed for residues of bens ulide and bensulide oxon using GC/FPD Method #CSI-009-02, with minor modifica tions including replacing nitrog en-phosphorus detection with flame photometric detection.Bensulide [PC Code 009801]/Gowan Company

EPA MRID #: 44435501 Page 4 of 5 Briefly, samples were extracted with toluene and centrifuged. The supernatant was filtered through sodium sulfate, then evaporated to dr yness by rotary evaporati on and reconstituted in
hexane. The hexane solution wa s partitioned three times with acetonitrile (ACN), and the ACN phases were combined and mixed with water, satura ted NaCl solution, and 2% citral in toluene. The resulting citral/toluene laye r was back-washed twice with wa ter/NaCl then filtered through sodium sulfate for analysis by GC/FPD.

The LOQ (determined as the LLMV) was 0.05 ppm for each analyte. The limit of detection (LOD) was not reported.

II. RESULTS AND DISCUSSION

Method performance was evaluated during method va lidation and by use of concurrent recovery.
For method validation and concurrent recovery, samples of tomato were fortified with bensulide and bensulide oxon, each at 0.05 and 5.0 ppm for me thod validation and at 0.05 and 1.0 ppm for
concurrent recoveries. Recoveri es were within the acceptable range of 70-120%; therefore, the method was considered valid for the analysis of be nsulide residues in/on tomato matrices (Table B.7.7.3.1-3). The fortification levels bracketed the measured resi dues. Concurrent recoveries were corrected for apparent residues in controls.

Based on representative calibration curves, the detector response was linear for tomato matrices (coefficients of determination for be nsulide and bensulide oxon were: r 2 ≥ 0.9982 and r 2

≥ 0.9974 within the range of 0.100-2.0 ng standard inje cted). Representative chromatograms of control samples, fortified samples, and tr eated samples were provided. The control chromatograms generally had no peaks of intere st above the chromatographic background. The fortified sample chromatograms contained only the analyte of interest, and peaks were symmetrical and well defined. Apparent residues in controls were below the LOQ (<0.05 ppm) for both analytes in/on all matri ces. The reported residue values were not corrected for apparent
residues in controls.

Table B.7.7.3.1- 3. Summary of Method Validation and Proce dural/Concurrent Recoveries of Bensulide and
Bensulide Oxon from Tomato Matrices.
Matrix Analyte Fortification Level (ppm) Sample size (n) Recoveries 1 (%) Mean ± Std. Dev. (%)

Method Validation

Tomato Bensulide 0.05-5.0 6 88-92 90 ± 1.5

Bensulide oxon 0.05-5.0 6 86-106 96 ± 7.9

Concurrent Recoveries

Tomato Bensulide 0.05-1.0 4 94-101 97 ± 3.0

Bensulide oxon 0.05-1.0 4 76-81 78 ± 2.4

1 Concurrent recoveries were corrected for apparent residues in controls.

Sample storage conditions and durations are su mmarized in Table B.7.7.3.1-4. Tomato samples were stored for 8 days between harvest and extraction for analysis. Samples were analyzed on the day of extraction. No storage stabili ty data are needed to support the study.Bensulide [PC Code 009801]/Gowan Company

EPA MRID #: 44435501 Page 5 of 5 Table B.7.7.3.1-4. Summary of Storage Conditions 1

. Matrix Analyte Storage Temperature Actual Storage Duration Interval of Demonstrated Storage Stability

Tomato\ Bensulide and
bensulide oxon ≤ 16 °F 8 days None needed.

1 Interval from harvest/processing to extraction. Samples were analyzed on the day of extraction.

Residues found in samples and processing factor s are given in Table B.7.7.3.1-5. Following a single preplant incorporated application of a 4 lb ai/gal EC formulation of bensulide at an exaggerated rate of 29.8 lb ai/A, residues of bensulide and bensulide oxon were each below the LOQ (<0.05 ppm) in/on all samples of tomato. Because residues were below the LOQ in/on all samples following exaggerated-rate (reportedly ~5x) application, no processing was conducted.

Table B.7.7.3.1-5. Residue Data from Tomato Processing Study with Bensulide.
Commodity Analyte Residues (ppm) [Average] 1 Processing Factor Median Processing Factor

Tomato (RAC) Bensulide <0.05, <0.05 [<0.05]
-- Bensulide oxon <0.05, <0.05 [<0.05]
--
1 The LOQ was 0.05 ppm for each analyte; the LOD was not reported. All values are the result of duplicate analyses and duplicate injections.

III. CONCLUSIONS

The tomato processing study is considered scientif ically acceptable. Following a single preplant incorporated application of a 4 lb ai/gal EC formulation of be nsulide at an exaggerated rate of 29.8 lb ai/A, residues of bensu lide and bensulide oxon were e ach below the LOQ (<0.05 ppm) in/on all samples of tomato. Because residues were below the LOQ in/on all samples following exaggerated-rate (reportedly ~5x) app lication, no processing was conducted.

The maximum theoretical processing factors fo r tomato are 1.4x and 5.5x for puree and paste (based on loss of water; OCSPP 860.1520, Table 2) and 1.4x for juice (based on separation into components; OCSPP 860.1520, Table 3).

An acceptable method was used for residue quantitati on; no storage stability data are required to support sample storage durations and conditions.

REFERENCES

Residue Chemistry Chapter of the Bensulide Reregistration Eligibil ity Decision, DP# 238417, C. Eiden, 9/11/97.