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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDE

AND TOXIC SUBSTANCES

MEMORANDUM

Date: January 21, 2010

SUBJECT: Fomesafen Sodium. Petition for the Establishment of Tolerances and Registration 

of New Uses on Potato and Tomato; and Response to Data Gaps for Conditional 

Registration on Cotton, Dry Bean, and Snap Bean. Summary of Analytical 

Chemistry and Residue Data.

PC Code: 123802 DP Barcodes: D365199 and D366116

Decision No.: 409397 and 415115 Registration No.: 100-993

Petition Nos: 9F7563 (potato and tomato),

1E6228 (dry bean), 9F5068 (cotton), and 6E4653

(snap bean)

Regulatory Action: Amended Section 3

Risk Assessment Type: NA Case No.: NA

TXR No.: NA CAS No.: 72178-02-0

MRID No.: See MRID Summary Table 40 CFR: §180.433

FROM: Christine L. Olinger, Chemist

Risk Assessment Branch VII

Health Effects Division (7509P)

THROUGH: Toiya Goodlow, Chemist

Michael S. Metzger, Chief

Risk Assessment Branch VII

Health Effects Division (7509P)

TO: Dan Kenny/Michael Walsh, PM Team 23

Herbicide Branch 

Registration Division (7505P)

MRID Summary Table

MRID No. Study Type Comments

47473901 860.1300 Tomato New DER; 47473901.der.doc

47473902 860.1500 Tomato Crop Field Trials New DER; 47473902.de1.doc

860.1520 Tomato Processing Study New DER; 47473902.de2.doc

47473903 860.1500 Potato Crop Field Trials New DER; 47473903.de1.doc

860.1520 Potato Processing Study New DER; 47473903.de2.doc

47761901 860.1360 Multiresidue Methods New DER; 47761901.der.doc

47761902 860.1380 Storage Stability New DER; 47761902.der.doc

47761903-04 860.1340 Residue Analytical Methods New DER 47761903.der.doc (Includes 

MRID 47761904)
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MRID Summary Table

MRID No. Study Type Comments

47761905 Response to Conditions of Registration No DER generated; registrant’s responses to 

deficiencies are incorporated in this 

Summary Document.

This document was originally prepared under contract by Dynamac Corporation (1901 Research 

Boulevard, Suite 220; Rockville, MD 20850). 

Dynamac QC 

Reviewer:

Date: 10/14/2009

Tracey Cowen

Dynamac Program 

Manager:

Date: 10/14/2009

Danilo Martinez

The document has been reviewed by the Health Effects Division (HED) and revised to reflect 

current Office of Pesticide Programs (OPP) policies.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Executive Summary

Fomesafen sodium is a contact broadleaf herbicide in the diphenylether chemical class. The 

herbicide acts through inhibition of the enzyme protoporphyrinogen oxidase (PPO) in plants. 

The active ingredient was originally registered on 09/11/1987 by Zeneca Ag Products and was 

transferred to Syngenta Crop Protection, Inc. on 02/23/2001. Fomesafen is currently registered 

for use on the crops cotton, dry beans, snap beans, and soybeans. It is applied to treat various 

broadleaf weeds, annual grasses, perennial weeds and sedges. 

Syngenta has proposed, in PP#9F7563, the establishment of permanent tolerances for residues of

fomesafen in/on the following raw agricultural commodities:

Potato ....................................................................................................... 0.025 ppm

Tomato ..................................................................................................... 0.025 ppm

In support of the proposed tolerances and new crop uses, Syngenta has submitted a tomato 

metabolism study and magnitude of the residue studies on potatoes and tomatoes. In addition, 

the petitioner has submitted various residue chemistry studies in response to the data gaps 

identified by as a condition of registration for a request previously made by Syngenta and IR-4 to 

amend the Reflex® Herbicide. This Summary Document addresses the adequacy of the 

submitted residue chemistry data in support of the proposed new uses on potatoes and tomatoes 

as well as the adequacy of Syngenta’s responses to the conditions of registration.

Reflex® Herbicide is proposed for one broadcast preemergence application on potatoes after 

planting but before potato emergence at a maximum rate of 0.25 lb ae/A and a 70-day preharvest 

interval (PHI). On tomatoes, Reflex® Herbicide is proposed for one broadcast preplant nonincorporated preemergence application up to 7 days prior to transplanting tomato seedlings at a 

maximum rate of 0.375 lb ae/A and a 70-day PHI.

The metabolism of fomesafen in soybean, cotton, and tomato has been investigated. The 

soybean and cotton metabolism studies were reviewed in DP# 325801, and the tomato study was 

included as part of the current petition package. The cotton metabolism study has now been 

upgraded to acceptable status based on Syngenta’s submission of the requested information. The 

terminal residue of concern in cotton is fomesafen. The tomato metabolism study is acceptable 

and supports the proposed use on tomatoes. The terminal residue of concern in tomatoes is 

fomesafen. 

HED generally recommends that three metabolism studies on diverse crops when a pesticide is to 

be used on several different commodities. Although three metabolism studies have been 

submitted, tomatoes, soybeans and cotton are not sufficiently diverse to define the nature of the 

residue in all crops. Since no data on a root crop have been provided that can be translated to the 

proposed use on potatoes, a potato metabolism study, in which both the root and tops/foliage are 

analyzed, is required to support the proposed use on potatoes. HED cannot recommend for a 

tolerance in/on potatoes until an adequate metabolism study is submitted.

There are no livestock feedstuffs associated with the proposed use on tomatoes. The nature of 

the residue in ruminants is adequately understood. At this time no tolerances have been 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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established on any livestock commodity in association with the existing uses of fomesafen. 

Livestock feeding studies are not required to support the proposed/registered uses of fomesafen. 

Syngenta should note that if additional uses are proposed in the future which result in an increase 

in the dietary burdens, livestock feeding studies may be required. 

Adequate residue analytical methods are available for the purpose of tolerance enforcement. 

Syngenta submitted a new high performance liquid chromatography method with tandem mass 

spectrometry detection (LC/MS/MS) method (GRM045.01A) as an enforcement method. The 

method uses extraction procedures similar to previous methods, SPE cleanup procedures, and the 

final determination step by LC/MS/MS technology for analysis of fomesafen residues. The 

validated limit of quantitation (LOQ) of the method is 0.02 ppm. Method GRM045.01A was 

adequately validated at fortification levels of 0.02 ppm and 0.2 ppm in snap beans, pinto beans 

(dry bean), corn oil, cotton, undelinted seed and gin byproducts, and soybean forage, hay, and 

aspirated grain fractions. Methods for the determination of fomesafen residues of concern in 

livestock commodities are not required at this time but may be required in the future. 

The requirements for multiresidue method testing data for fomesafen are fulfilled. FDA 

multiresidue methods are not suitable for determining residues of fomesafen; the submitted data 

will be forwarded to U.S. FDA for further evaluation. 

Samples of raw and processed commodities of potatoes and tomatoes, which were collected from 

the magnitude of the residue studies, were analyzed for residues of fomesafen using a 

LC/MS/MS based on an liquid chromatography with ultraviolet detection (HPLC/UV) method 

(GAM-RM-001/86). The method was adequately validated during concurrent analysis of 

samples. The lowest level of method of validation (LLMV) was 0.025 ppm for each matrix. 

Analytical standards for fomesafen are currently available in the EPA National Pesticide 

Standards Repository.

Adequate storage stability data are available to support the storage conditions and durations of 

samples collected from the magnitude of the residue studies on tomatoes. Interim storage 

stability data were additionally submitted for various crop commodities in response to a data gap 

cited in DP# 325801, and the registrant intends to submit a final report with analyses after 18 and 

24 months of storage. Residues of fomesafen appear to be relatively stable in/on corn, wheat, 

soybean, and cotton commodities through 13 months of storage.

The submitted field trial data for fomesafen on tomatoes are acceptable and support the proposed 

uses. An adequate number of trials were conducted in the appropriate geographic regions at ~1x 

the maximum proposed rate using Reflex® Herbicide, and the appropriate samples were 

collected from each test around the proposed PHI. All treated samples bore residues below the 

LLMV (<0.025 ppm). Based on these data, HED recommends a tolerance of 0.025 ppm for 

residues of fomesafen in/on tomatoes.

Provided the requested metabolism study does not indicate that there are additional 

metabolites/degradates of concern, an adequate number of field trials were conducted to support 

the proposed new use on potatoes. Residues of fomesafen were below the LLMV of 0.025 ppm

in all trials. HED reiterates that a root/tuber metabolism study is required to support this use. If 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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the new study identifies additional residues of concern, then additional field trials reflecting 

analysis of the new residues will be required to support this use.

The previously submitted cotton field trial data have now been upgraded to acceptable status 

based on Syngenta’s submission of the requested information pertaining to weather conditions, 

soil characteristics, and raw data of field notes, calibration of equipment, and sampling 

procedures that were employed in the conduct of the cotton trials. The Agency concludes that 

adequate residue data are available to support the established tolerances of 0.025 ppm each for

cotton gin byproducts and undelinted cottonseed.

The results of submitted potato and tomato processing studies show that residues of fomesafen 

were each below the LLMV (<0.025 ppm) in/on the respective RACs following application of 

Reflex® Herbicide at 1x. Since the studies involved processing of RACs bearing 

nonquantifiable residues, no measurable processing factors can be calculated. Although, the 

Agency would have preferred the use of exaggerated rates in the conduct of the processing 

studies to yield RACs with quantifiable residues, HED will not require additional processing data 

at this time.

The nature of the residue in rotational crops remains inadequately understood. Syngenta has 

previously been requested to conduct a new confined rotational crop study reflecting separate 

application of CP- and NP-label fomesafen at the maximum seasonal application rate to rotatable 

crops. According to Syngenta, a new confined rotational crop study is ongoing and will be 

completed by 12/31/2009. Satisfaction of the confined rotational crop data should be a condition 

of these registrations.

At this time, data are not available to support rotation to other crops beyond those commodities 

that are currently registered and proposed as primary crops; therefore, the registrant must revise 

the Reflex® Herbicide label to permit immediate replanting of soybeans, cotton, dry beans, snap 

beans, potatoes, and tomatoes only with a restriction that other crops can only be planted 12 

months after treatment or 18 months after treatment if based on phytotoxicity concerns.

No Codex, Canadian, or Mexican MRLs have been established for residues of fomesafen in/on 

potato or tomato. Canadian MRLs have been established for residues of fomesafen in/on dry

beans, lima beans, snap beans, and soybeans at 0.05 ppm, and a Mexican MRL of 0.05 mg/kg 

has been established for residues of fomesafen in/on soybeans. The registrant has advised the 

Agency that they intend to petition the Canadian government for revised tolerances to address 

any potential harmonization issues raised by establishing the new tolerances requested in this 

action.

Regulatory Recommendations 

HED has examined the residue chemistry database for fomesafen sodium. Pending resolution of 

the deficiency pertaining to directions for use and provided the submission of a confined 

rotational crop study is made a condition of the registration, there are no residue chemistry issues 

that would preclude granting the petitioner’s request to amend the Reflex® Herbicide label for

the purpose of adding the requested use on tomatoes. HED recommends a conditional 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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registration for this herbicide on the crops requested and/or the revision of 40 CFR §180.433 for 

the establishment of tolerances for residues of fomesafen as follows:

Tomato ..................................................................................................... 0.025 ppm

The registrant’s most recent Reflex® Herbicide label reflects regional use of fomesafen on 

tomatoes. However, the residue chemistry data submitted in support of this action are of 

sufficient geographic representation to support full U.S. registration; therefore, HED 

recommends that these tolerances be listed in the general section of 40 CFR §180.433.

Tolerances for fomesafen residues are listed in 40 CFR §180.433. Currently, the single 

established tolerance is expressed in terms of “sodium salt of fomesafen, 5-[2-chloro-4-

(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide.” HED has determined that the 

residue of concern for tolerance expression is fomesafen. Therefore, the established tolerance 

expression should be revised to be expressed in terms of fomesafen, by removing the phrase 

“sodium salt of” from 40 CFR §180.433(a).

Note to PM: According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. 

Knizner), the tolerance expression for fomesafen should be revised to state:

“Tolerances are established for residues of fomesafen, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only fomesafen [5-[2-chloro-4-

(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide].”

A human health risk assessment is forthcoming.

Residue Chemistry Deficiencies

Deficiencies - Tomato Petition (9F7563)

The following deficiency must be resolved prior to granting of the registration on tomatoes.

860.1200 Directions for Use

· At this time, data are not available to support rotation to other crops beyond those 

commodities that are currently registered and proposed as primary crops; 

therefore, the petitioner must revise the Reflex® Herbicide label to permit 

immediate replanting of soybeans, cotton, dry beans, snap beans, potatoes, and 

tomatoes only with a restriction that other crops can only be planted 12 months 

after treatment or 18 months after treatment if based on phytotoxicity concerns.

The deficiency listed below must be fulfilled as a condition for the registration of Reflex® 

Herbicide label to add the requested use on tomatoes.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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860.1850 Confined Accumulation in Crops

· The ongoing confined rotational crop study, which is expected to be completed by

12/2009, should be submitted at the earliest possible convenience. Based on this 

future submission, HED will determine the terminal residues of concern in 

rotational crops and will re-evaluate the existing field rotational crop studies for 

determination of appropriate plantback restrictions.

Deficiencies - Potato Petition (9F7563)

HED cannot recommend for the requested tolerance in/on potatoes due to the lack of an adequate 

root/tuber metabolism study. The following study must be submitted to support the proposed 

tolerance.

860.1300 Plant Metabolism

· A potato metabolism study in which both the roots and tops are analyzed is 

required to support the proposed use and tolerance on potatoes.

Remaining Deficiencies – PP#s 1E6228 (Dry Bean), 9F5068 (Cotton), and 6E4653 (Snap Bean) 

All data gaps previously identified by HED (DP# 325801, 4/25/2006, D. Davis) as a condition of 

registration under the petitions cited above have now been adequately fulfilled except for the 

requirements for confined rotational crop data noted above as well as the deficiency pertaining to 

storage stability listed below.

860.1380 Storage Stability

· The registrant intends to submit a final storage stability report, including analyses 

at 18 and 24 months. When this study is submitted the registrant should ensure 

that the dates documented in the report should reflect the actual storage intervals, 

and not the proposed intervals, as there was some discrepancy in the interim 

report.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Background

The chemical name and structure of fomesafen sodium and fomesafen are listed below in Table 

1. The physicochemical properties of fomesafen are listed in Table 2; data pertaining to the 

physicochemical properties of fomesafen sodium are not available.

Table 1. Test Compound Nomenclature.

Compound

F3C

Cl

O

NO2

O

N

S

CH3

O

O

Na

+

Common name Fomesafen Sodium

Company experimental name Not provided.

IUPAC name 5-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-N-methylsulfonyl-2-nitrobenzamide, sodium salt

CAS name 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitro-benzamide, sodium 

salt

CAS registry number 108731-70-0

Compound F3

C

Cl

O

NO2

O

N

H

S

CH3

O

O

Common name Fomesafen

Company experimental name Not provided.

IUPAC name 5-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-N-methylsulfonyl-2-nitrobenzamide

CAS name 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide

CAS registry number 72178-02-0

End-use product (EP) Reflex® Herbicide, 2 lb ae/gal SL; EPA Reg. No. 100-993

Table 2. Physicochemical Properties of Fomesafen.

Parameter Value Reference

Melting point/range 220-221 C HED Memo, 9/3/82, W. Anthony

pH 8.2 (94% TGAI) CSF (EPA Reg. No. 100-1017; 10/13/00)

Density 1.28 g/cm3

at 20 C HED Memo, 9/10/86, C. Trichilo

Water solubility at 25 °C 600 g/L at pH 7

<10 ppm at pH 1-2

50 mg/L

HED Memo, 9/3/82, W. Anthony

HED Memo, 9/10/86, C. Trichilo

Solvent solubility g/L

Acetone 300

Cyclohexanone 150

Methanol 25

Hexane 0.5

Xylene 1.9

HED Memo, 9/10/86, C. Trichilo

Vapor pressure <7.5 x 10-7 mm Hg at 50 C The Pesticide Manual 1

Dissociation constant, pKa 2.7 at 20 C
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Table 2. Physicochemical Properties of Fomesafen.

Parameter Value Reference

Octanol/water partition 

coefficient, Log(KOW)

Log KOW = 2.9 at pH 1

UV/visible absorption spectrum Not available

1 The Pesticide Manual, A World Compendium, The British Crop Protection Council (toxnet.nlm.nih.gov).

860.1200 Directions for Use

The end-use product relevant to the potato and tomato petition (PP#9F7563) is Reflex® 

Herbicide (EPA Reg. No. 100-993), a soluble concentrate liquid (SL) formulation containing 

22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of fomesafen). 

Reflex® is a selective herbicide which may be applied preplant surface, preemergence, and/or 

postemergence for control or partial control of broadleaf weeds, grasses, and sedges in registered 

crops cotton, dry beans, snap beans, and soybeans. In support of the proposed uses on potatoes 

and tomatoes, the petitioner submitted a draft label for Reflex® Herbicide dated 4/27/2009. A 

summary of the proposed use directions for potatoes and tomatoes is presented in Table 3A.

Table 3A. Summary of Proposed Use Directions of Reflex® Herbicide (EPA Reg. No. 100-993; 2 lb ae/gal) 

on Potatoes and Tomatoes.

Applic. Timing, Type, and 

Equip.

Applic. 

Rate 

(lb ae/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ae/A)

PHI

(days) Use Directions and Limitations

Potato

Broadcast preemergence 

application after planting but 

before potato emergence

Ground/Aerial/Center pivot 

irrigation 

0.25 1 0.25 70

Refer to Syngenta’s Regional Use 

Map for Reflex® 1(summarized 

in the ‘General Use Directions’ 

below) for determination of 

maximum use rate that may be 

applied in each geographic 

region. Do not apply to any field 

in Regions 2, 3, 4, or 5 more than 

once every two years. Do not 

apply to sweet potatoes or yams. 

Do not apply as a preplant 

incorporated application as crop 

injury may occur. Do not apply 

to emerged potato plants or 

severe crop injury will occur.

Tomato (Transplanted)

Broadcast preplant nonincorporated preemergence 

application up to 7 days prior 

to transplanting tomatoes

Ground/Aerial/Center pivot 

irrigation

0.25-

0.375 1 0.375 70

Refer to Syngenta’s Regional Use 

Map for Reflex® 1(summarized 

in the ‘General Use Directions’ 

below) for determination of 

maximum use rate that may be 

applied in each geographic 

region. Do not apply to any field 

in Regions 2, 3, 4, or 5 more than 

once every two years.

1

 The draft label specifies five use regions with specific seasonal maximum application rates. The rates range with the label use 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Region 1 having the highest seasonal application rate reflects application at 0.375 lb ae/A each year and label use Region 5 

with the lowest seasonal application rate reflects application of up to 0.1875 lb ae/A in alternate years. Details of the 

seasonal maximums for all label use Regions are presented below under “General Use Directions”.

General Use Directions

Syngenta’s regional use map for Reflex®: The draft label specifies that product may only be 

used in the eastern half of the U.S. Syngenta’s regional use map for Reflex® is subdivided into 

the following five regions:

Region 1: Reflex® may be applied at a maximum of 0.375 lb ae/A per year in Region 1 per year 

which includes the following states or portion of states: AL, AR, FL, GA, LA, MS, MO 

(counties of Bollinger, Butler, Cape Girardeu, Dunklin, Madison, Mississippi, New Madrid, 

Pemiscot, Perry, Ripley, Scott, Stoddard, and Wayne), NC, OK (East of U.S. Highway 75 and 

East of Indian Nation Parkway), SC, TN, and TX (includes area East of U.S. Highway 77 to State 

Road 239 including all of Calhoun County).

Region 2: Reflex® may be applied at a maximum of 0.375 lb ae/A in alternate years in Region 2 

which includes the following states or portion of states: DE, KY, MD, VA, WV, and South of 

Interstate 70 in the following states: IL, IN, and OH and all areas South of the Interstate 80 to the 

intersection of U.S. Highway 15 and East of U.S. Highway 15 and U.S. Highway 522 in PA.

Region 3: Reflex® may be applied at a maximum of 0.313 lb ae/A in alternate years in Region 3 

which includes the following states or portion of states: CT, IA, ME, MA, MO (all counties 

except those listed in Region 1), NH, NJ, NY, PA (all areas except those listed in Region 2), RI, 

VT, and WI (South of U.S. Highway 18 between Prairie Du Chien and Madison, and South of 

Interstate 94 between Madison and Milwaukee), and North of Interstate 70 in the following 

states: IN, IL, and OH. 

Region 4: Reflex® may be applied at a maximum of 0.25 lb ae/A in alternate years in Region 4 

which includes the following states or portion of states: KS (all counties East of or intersected by

U.S. Highway 281), MI (Southern Peninsula), MN (all areas South of Interstate 94), NE (all 

counties East of or intersected by U.S. Highway 281), and WI (all areas, except those in Region 

3, South of Interstate 94 from MN state line to Eau Claire and South of U.S. Highway from Eau 

Claire to Green Bay plus Barron, Chippewa, Clark, Door, Dunn, Eau Claire, Kewaunee, 

Marathon, Menominee, Oconto, Polk, Shawano, and St. Croix counties. The following counties 

are excluded: Adams, Marquette, Portage, Waupaca, Waushara, and Wood). ND (all areas East 

of Interstate 29 from Fargo South to the SD state line). SD (all areas East of Interstate 29 from 

the ND state line to Watertown, all areas East of Highway 81 from Watertown to Madison and 

all areas East and South of State Road 34 and U.S. Highway 281 to the NE state line.

Region 5: Reflex® may be applied at a maximum of 0.1875 lb ae/A in alternate years in Region 

5 which includes the following states or portion of states: ND (all areas East of the U.S. 

Highway 281 except those areas in Region 4), SD (all areas East of the U.S. Highway 281 except 

those areas in Region 4), and MN (all areas South of the U.S. Highway 2 except those areas in 

Region 4).
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Spray additives: The draft label specifies that spray additives cleared for use on growing crops 

under 40 CFR §180.1001 may be used in the spray mixture. A nonionic surfactant (NIS), crop 

oil concentrates (COC), or other adjuvants may be used for postemergence applications only. 

Since the proposed uses on potatoes and tomatoes are either preemergence or pretransplant, the 

use of surfactants is not needed when Reflex® is applied to these crops.

Application equipment: Ground applications are to be made in a minimum of 10 gal/A, and 

aerial applications are to be made in a minimum of 5 gal/A. Applications are not to be made 

through any type of irrigation equipment except center pivot systems. Reflex® alone or in tank

mixture with other herbicides on the label, which are registered for center pivot application, may

be applied in irrigation water preemergence (after planting but before weeds or crop emerge) at 

label-recommended rates.

Tank mixtures with other products registered for use on potatoes and tomatoes: The draft label 

provides mixing procedures for tank mixes but does not specify specific tank mix partners for 

potatoes and tomatoes. The use directions state that, for tank mix combinations, the 

recommendations, restrictions, and limitations for all products must be followed and that the 

most restrictive labeling is to apply. For preemergence application in potatoes, Reflex® may be 

tank mixed with other pesticide products registered for use in this way and timing in potatoes. 

For preplant non-incorporated preemergence applications prior to transplanting tomatoes, 

Reflex® may also be tank mixed with other pesticide products registered for use in this way and 

timing in tomatoes. 

Rotational crop plantback intervals: The draft label specifies that the rotational crops listed in 

Table 3B may be planted after applying Reflex® at recommended rates.

Table 3B. Rotational Crop Plantback Intervals Listed on the Reflex® Herbicide.

Crop To Be Planted Minimum Rotation Interval

(Months After Last Reflex® Application)

Cotton, dry beans, potatoes, snap bean, soybeans, and 

transplanted tomatoes

0

Small grains such as wheat, barley, and rye 4

Corn 1, peanuts, peas, rice, seed corn 10

To avoid crop injury, do not plant alfalfa, sunflowers, sugar beet, 

sorghum 2, or any crop within

18

1 Use a 12 month minimum rotation interval for popcorn in the states of OH, KY, IL, IN, IA, and Region 4 when 

applied at rates of 0.25 lb ae/A or more. Use 18 month minimum rotation for sweet corn in the states of CT, ME, 

MA, NH, NY, RI, VT, and Region 5.

2

 Sorghum may be planted back after 10 months in Region 1.

Additional consideration: HED previously requested (DP# 325801, 4/25/2006, D. Davis) that 

the product label for Reflex® Herbicide be revised to reflect a 45-day PHI for dry beans based on 

the submitted data and remove Frontier as a recommended tank mix partner for snap beans. An 

examination of the draft label for Reflex® Herbicide indicates that a 45-day PHI is now listed for 

dry beans and Frontier is no longer listed as a tank mix partner for snap beans; therefore, this data 

gap is fulfilled.

Conclusions. The available draft label for Reflex® Herbicide is adequate to allow evaluation of 

residue data relative to the proposed use on potatoes and tomatoes.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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At this time, data are not available to support rotation to other crops beyond those commodities 

that are currently registered and proposed as primary crops; therefore the petitioner must revise 

the Reflex® Herbicide label to permit immediate replanting of soybeans, cotton, dry beans, snap 

beans, potatoes, and tomatoes only with a restriction that other crops can only be planted 12 

months after treatment or 18 months after treatment if based on phytotoxicity concerns.

860.1300 Nature of the Residue - Plants

Tomato

DER Reference List: 47473901.der.doc

Syngenta Crop Protection has submitted a study investigating the metabolism of 

[trifluoromethylphenyl-U14C]fomesafen (TMP label; specific activity 55.8 μCi/mg) and 

[nitrophenyl-U14C]fomesafen (NP label; specific activity 56.2 μCi/mg) in tomatoes. Each 

radiolabeled test substance was formulated as ReflexTM Herbicide in water and applied by

spraying onto the bare ground soil of designated plots, four days before tomato seedlings were 

transplanted into the plots. The target application rate was 0.375 lb ai/A (1x the proposed rate). 

Actual application rates were 0.369 lb ai/A for the TMP label and 0.385 lb ai/A for the NP label. 

Ripe tomatoes were harvested 98 days after treatment (DAT). A second harvest, 104 DAT, 

provided additional red ripe fruits and immature green fruits (both not analyzed) and foliage for 

analysis that might generate more information of the metabolism of the test substance. The field 

phase of the study was conducted at an outdoor field site maintained by Excel Research Services 

(Fresno, CA). The analytical phase of the study was performed by PTRL West, Inc. (Hercules, 

CA).

Total radioactive residues (TRR) in tomato matrices were determined by both combustion and 

the sum of ppm levels detected in extracts and the post-extraction solids (PES). The TRR in ripe 

tomatoes were very low (0.005 and 0.002 ppm for the TMP and NP labels, respectively). The 

TRR in tomato foliage (0.084 and 0.080 ppm for the TMP and NP labels, respectively) were at 

least 17x higher than fruits.

Residues in harvested matrices were extracted with acetonitrile:water (1:1, v:v) twice, a 

procedure which adequately released the majority of radioactivity. Additional extraction with 

acetonitrile released no radioactivity, and the post-extractions solid (PES) was devoid of 

radioactivity as demonstrated by combustion. The combined acetonitrile:water extracts were 

analyzed by HPLC, which showed numerous products that generally partitioned into water rather 

than organic solvent (ethyl acetate). The combined acetonitrile:water extracts were acidified (pH 

~1) and extracted with ethyl acetate to characterize/identify residues by chromatographic 

techniques. 

From the TMP label study, the parent fomesafen was identified in fruits (3.7% TRR) and foliage 

(2.4% TRR). In addition, the metabolite 3-chloro-4-hydroxybenzoic acid (R052850) was 

detected in fruits (5.5-6.9% TRR) but not in foliage. A major unknown (up to 78.4% TRR) was 

characterized as acid labile, to volatile residues. All identified residues were below 0.01 ppm. 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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From the NP label study, fomesafen was identified in fruits (3.6% TRR) and foliage (1.3% TRR). 

Approximately 39.6% of the TRR in the extract eluted at the solvent front and 31.6% at retention 

time 12.8 minutes. When the concentrated extract was partitioned between ethyl acetate and 

water (pH ~4), all radiolabel was in the aqueous phase. The extract was reanalyzed by HPLC 

when two cysteine (Cys) conjugates became available as reference standards. The peak at ~13 

min co-eluted with the Cys conjugate of sulfonamide (R290493) and was detected in fruits (31.1-

31.6% TRR) and foliage (8.8% TRR). The following metabolites were additionally identified: 

(i) 2-NO2-5-OH benzoic acid (R012156) in fruits (5.9% TRR); and (ii) 2-NH2-5-OH benzoic acid 

(R089135) in fruits (3.7% TRR). 

Tomato fruits and foliage were stored frozen for maximum durations of 70 and 36 days, 

respectively, prior to the completion of chromatographic analyses. No storage stability data were 

submitted and none are required since sample integrity was maintained by appropriate freezer 

storage and final analysis was completed within 70 days of sample collection.

Based on the results of the conducted study, the petitioner provided a proposed metabolic 

pathway of fomesafen in tomato. As also found in a concurrent confined accumulation study in 

rotational crops, the ether bridge is cleaved by a nucleophilic addition of glutathione with 

subsequent formation of cysteine conjugate(s) of the nitro-[

14C-U-phenyl] moiety and 

conjugation and/or oxidation of the trifluoromethyl-[

14C-U-phenyl] moiety as well as formation 

of polar weak acid metabolites of each ring moiety. 

14C-Incorporation into very polar natural 

products is also likely. According to the petitioner, these findings are also similar and consistent 

with previous metabolism work reported on fomesafen and acifluorfen (an analogous diphenyl 

ether herbicide) with soybean foliage and cotton. See Appendix II for the chemical names and 

structures of metabolites identified.

Conclusions. The submitted tomato metabolism study is adequate. TRR in ripe tomatoes were 

very low (0.005 and 0.002 ppm for the TMP and NP labels, respectively) following application 

of the test substances at a target rate of 0.375 lb ai/A. In ripe tomatoes, fomesafen (3.6-3.7% 

TRR) was identified as were the metabolites 3-chloro-4-hydroxybenzoic acid (R052850) (5.5-

6.9% TRR), 2-NO2-5-OH benzoic acid (R012156) (5.9% TRR), and 2-NH2-5-OH benzoic acid

(R089135) (3.7% TRR). The cysteine conjugate of sulfonamide (R290493) was a major product 

from the NP radiolabel (31.1-31.6% TRR). A major unknown from the TMP radiolabel (up to 

78.4% TRR) was characterized by the registrant as acid labile, to volatile residues. Although the 

corresponding %TRR appears high for characterized/identified components, all residues were 

below 0.01 ppm. Residues in the rest of the tomato plant (foliage/stalks) was >10x higher than in 

fruit and generally consisted of fomesafen and the same metabolites.
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Syngenta’s Response to Cotton Metabolism Study Data Gaps as a Condition of Registration

Reference List: 47761905 (No DER generated)

HED previously reviewed (DP# 325801, 4/25/2006, D. Davis) a cotton metabolism study (MRID 

44754706) submitted by Syngenta in support of a cotton tolerance petition (PP#9F5068). 

Although the study was deemed unacceptable to fulfill data requirements, HED concluded that 

the cotton study may be upgraded pending submission of additional information pertaining to the 

conduct and other experimental details. In response, Syngenta has submitted MRID 47761905 

which provides responses to the information requested. The specific deficiencies are re-stated 

below followed by the petitioner’s response and HED’s comments regarding the adequacy of 

response.

Deficiency: “The actual application rate for the higher treatment rate must be provided 

(Syngenta only provided the target application rate for plants treated at 1.5 lb ai/A). The lighting 

and temperature conditions used in the greenhouse should be provided.”

Syngenta’s response: Sample calculations included in the cotton metabolism report indicated 

that 2.15 mCi and 2.47 mCi [2-chloro-4-(trifluoromethyl)phenoxy-U14C] and 2-

[nitrobenzamide-U14C]fomesafen, respectively, at specific activities of 54.5 and 62.5 Ci/mol

were required to achieve an application rate of 1.5 lb ai/A to the test pots. Dosing solutions for 

each label were confirmed by scintillation counting of aliquots. Application of [2-chloro-4-

(trifluoromethyl)phenoxy-U14C]fomesafen (CF3 label) was made to three pots and determined to 

be equivalent to 1.51, 1.51 and 1.51 lb ai/A. Application of 2-[nitrobenzamide-U14C]fomesafen

(NO2 label) was also applied to three pots at rates of 1.55, 1.55 and 1.56 lb ai/A. Calculations of 

application rates are presented in Table 4.
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Table 4. Amount of the Test Substance Applied to the Soil (3x Treatment).

(Note: table was copied directly from MRID 47761905.)

The exaggerated application rates (3x) were included in the study for the sole purpose of

generating adequate residues for characterization and identification. Documentation supporting 

the higher application rate was included in the study notebooks and raw data. 

Lighting and temperature conditions in the greenhouse were adjusted periodically to minimize 

temperature shifts. Hygrothermograph records maintained in the laboratory notebook indicate 

that typical temperatures ranged 77-98 °C. Lamps were used to irradiate the plants during early

morning (7 am-11 am) and mid-afternoon to evening (3 pm-11 pm). As warmer weather arrived, 

lamp schedules were changed to 6 am-9 am and 4 pm-10 pm to reduce the heat in the 

greenhouse. Typical plant heights were observed at harvest. All harvested crops were grown to 

maturity in good health and yield.

HED’s comments/conclusions: The petitioner has provided the calculations of the higher 

treatment rate used in the cotton metabolism study. The actual 3x applications rates were 1.51 

and 1.55-1.56 lb ai/A for the CF3 and NO2 labels, respectively. The requested information 

pertaining to lighting and temperature conditions used in the greenhouse was provided and 

appeared optimum for the type of study conducted. This deficiency is resolved.
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Deficiency: “Syngenta must provide the dates of sample analysis for all samples and all 

analyses. If final analyses of cotton gin byproduct samples were not completed within 6 months 

of sample collection, Syngenta must provide evidence that the metabolite profile in samples did 

not change during storage. We note that based on the study completion date, samples may have 

been stored >500 days prior to final analysis.”

Syngenta’s response: The RACs collected from cotton test plots treated with 14C-fomesafen 

were extracted, chromatographically profiled, and quantified within 3.5 months of harvest. 

Additional analysis of the samples was conducted beyond this point in order to isolate and 

characterize the radioactive residues. Comparison of chromatography obtained towards the end 

of the analytical phase of the study indicated a qualitatively similar chromatographic profile, thus 

providing evidence for storage stability.

Cotton plants treated with CF3 and NO2 labeled fomesafen were grown to maturity, harvested 

and separated into seed/fiber and gin byproducts. TRR in seeds from treatment at 0.5 lb ai/A 

were below 0.01 ppm for both labels and were not extracted or profiled. The TRR in gin 

byproducts from cotton treated with either test compounds at both the 0.5 and 1.5 lb ai/A 

application rates were >0.01 ppm. The samples were extracted, profiled, and quantified in two 

chromatographic systems within 3.5 months of harvest (page 16 of MRID 47761905). The 

cotton gin byproduct extracts from the two 3x treatment samples were further analyzed to 

characterize the radioactive residues.

In an effort to further characterize metabolites B, C, and D from the CF3 labeled fomesafen 

treated gin byproducts, the aqueous extract from the 3x treatment was subjected to semi-prep 

HPLC in January 1998 (page 17 of MRID 47761905). The HPLC method employed in semiprep analysis of this extract was similar in nature to the HPLC method used to generate the initial 

profiles (RR 97-056B). Therefore, a comparison of the two resulting chromatograms (page 20 of 

MRID 47761905) can be made for storage stability purposes. Such a comparison demonstrates 

the extracts are qualitatively similar and, as such, provides evidence, that the extract was stable 

under storage conditions.

Syngenta reported that approximately 10 months after harvest, an additional analysis was 

conducted with the aqueous extracts of gin byproducts treated with NO2 labeled fomesafen at the 

3x rate in an attempt to characterize metabolite G. Metabolite G, isolated from an aqueous 

extract, was subjected to hydrolysis and was characterized by HPLC as a complex mixture of 

products. No storage stability data were collected to support this work. Metabolite G, however, 

only represented 0.006 ppm (13.9% TRR) in gin byproducts treated at the 1x rate; thus, 

additional characterization of this minor radioactive residue was not necessary. Therefore, 

Syngenta believes that the lack of storage stability data for this sample does not impact any of the 

report conclusions.

HED’s comments/conclusions: The petitioner has provided the requested dates of sample 

analysis for all samples and all analyses. Based on these dates, all samples were extracted, 

profiled, and quantified within 3.5 months of harvest. Efforts to further analyze the aqueous 

extracts of gin byproducts treated at the 3x rate did result in analytical work being conducted 

more than 6 months after harvest. In the case of the extracts coming from treatment with the 

NO2 labeled fomesafen, no viable results in the characterization of the residues were obtained 
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due to low residue levels. HED concurs with Syngenta’s assessment that comparison of the 

resulting chromatography from the aqueous extracts of gin byproducts resulting from CF3 labeled 

fomesafen provided a qualitative profile similar to the definitive profile obtained within 6 months 

of harvest and, therefore, provides evidence of storage stability. This deficiency is resolved.

Deficiency: “There was a large difference between the total extractable radioactivity and the 

total of the identified and characterized radioactivity for each sample. For samples treated at the 

lower rate, Syngenta referred to this “fraction” as “total % unknown.” The total unknown 

fraction ranged 11.0-49.5% TRR (0.009-0.112 ppm) in gin byproduct samples. No explanation 

was provided. Syngenta also did not provide any quantitative chromatographic raw data. 

Syngenta must provide an explanation for this apparent loss in radioactivity. In addition, 

quantitative chromatographic data should be provided for all chromatograms included in the 

submission.”

Syngenta’s response: The exaggerated application rate (3x) samples were generated for the sole 

purpose of ensuring adequate radioactive residues were available to aid in characterization and 

identification. As such, the material balance was quantitated on the 1x treatment rate. Unknown 

constituents in the 1x and 3x applications are an accumulation of unresolved peaks and

background radioactivity. To illustrate this point, raw data were used to recreate the quantitation 

of the CF3 label and NO2 label (1x) organic and aqueous profiles and were presented in Figures 2 

and 3 MRID 47761905, respectively. These profiles illustrated that unknown peaks constitute 

multiple minor components and background radioactivity. All residues, except fomesafen, were 

at or below trigger (≤0.010 ppm) in the organic profiles. All residues, except metabolite C, were 

at or below trigger (≤0.010 ppm) in the aqueous profiles. Fomesafen, metabolite C, and 

metabolite D were isolated for characterization and identification by mass spectrometry.

Quantitation of unknown peaks in the exaggerated application rates was not pursued as the study

objective was to use these 3x treated crop fractions for isolation, if necessary. Chromatographic 

quantitation of the CF3 labeled fomesafen (1x) unknowns had 0.020 ppm residue which consisted 

of multiple minor components, none of which, except metabolite C, had individual residues of

>0.010 ppm. No unknown residues (>0.010 ppm) requiring further characterization were present 

in NO2 labeled fomesafen (1x) samples.

HED’s comments/conclusions: The petitioner responded to the above deficiency by recreating 

the quantitation of organic and aqueous extracts of cotton gin byproducts from the 1x study of the

CF3 label and NO2 label. The unknowns comprised 32% and 8.9% TRR of the CF3 and NO2

labels, respectively. Chromatographic quantitation of the CF3 labeled fomesafen unknowns 

consisted of multiple minor components, none of which, except metabolite C, had individual 

residues of >0.010 ppm. No unknown residues (>0.010 ppm) requiring further characterization 

were present in NO2 labeled fomesafen (1x) samples. Total accountability of residues in gin 

byproducts treated at 1x was re-calculated at 106% and 90% the CF3 and NO2 labels, 

respectively. This deficiency is resolved.

Deficiency: “Syngenta should provide an interpretation of the LC/MS spectra that were included 

in the submission for Metabolites B-3 and C-1 and provide proposed structures for these 

metabolites, if possible.”
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Syngenta’s response: Structures were suggested in the raw data files but were not included in the 

final report as the data to support structural confirmation were limited. A possible structure for 

Metabolite B-3 is shown in Figure 1 while that for Metabolite C-1 is shown in Figure 2. 

Syngenta offered some possible interpretations below which are consistent with the proposed 

structures.

Mass spectra for both peaks (B-3 and C-1) showed that they are chlorinated (based on the isotope 

pattern of the base peak); they also suggest that they are radiolabeled (based on the A+12 peak 

from the fully labeled phenyl ring). Therefore both rings are confirmed to be intact for both 

moieties.

The spectrum for metabolite B-3 (Figure 1) showed a m/z 459 peak in negative electro spray

ionization (ESI) consistent with the deprotonated sodium salt formed by loss of the acidic proton 

of the sulfonylbenzamide functionality; i.e., [M-2H+Na]

-

. An MS/MS experiment showed a

cleavage product ion at m/z 241 and a product ion at m/z 423 from loss of HCl that was

consistent with the dibenzodioxin product structure in Figure 4. Syngenta opined that this type 

of intramolecular cyclization with loss of HCl is a common process.

The negative electrospray spectrum for metabolite C1 showed a deprotonated molecule at m/z 

425, which was consistent with an aryl sulfate conjugate structure as shown in Figure 2. MS/MS 

product ions were observed at m/z 329 (loss of –SO4) and m/z 393 (loss of 2 oxygens); as well as, 

m/z 97 (HSO4

-

) and m/z 80 (SO3

-

). Because of the rare occurrence of sulfate conjugates observed 

from the metabolism of pesticides in plants, further evidence of structure C1 would be required 

before this structure could be assigned with confidence. Furthermore, ambiguities observed in 

the MS data; for example, missing chlorine isotopes and the apparent losses of multiple (3) units 

of 16, demonstrate that the experiments were being conducted near the performance limits of the 

instrument with respect to signal intensity and chemical noise. However, given the low residue

levels in the samples and limited capabilities of available LC/MS instruments, compared to 

today’s standards, the MS data represent the best possible results at the time the study was 

conducted, and no additional supporting data was obtainable.

HED’s comments/conclusions: The petitioner responded to the above deficiency by assigning 

possible structure for Metabolites B-3 (Figure 1) and C-1 (Figure 2). This deficiency is resolved.

Deficiency: “Syngenta should provide an explanation for not making any attempts to 

characterize the nonextractable radioactivity in gin byproducts treated with NP label 

[

14C]fomesafen at the higher rate. According to the requirements of OPPTS 860.1300, additional 

attempts to extract this radioactivity should have been made (nonextractable radioactivity was 

>10% TRR and >0.05 ppm).”

Syngenta’s response: The NO2 label fomesafen samples (3x) were generated to ensure adequate 

residues for identification and characterization. No additional attempts were made to 

characterize the non-extractable radioactivity for gin byproducts treated with NO2 label 

fomesafen at the higher rate because of the low residue (0.011 ppm) at the 1x rate.

HED’s comments/conclusions: HED concurs with Syngenta that no further characterization of 

nonextractable residues in gin byproducts treated with NP label [14C]fomesafen at the higher rate 
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is required because of the low residues at the 1x rate. HED will consider the residue 

characterization of cotton RACs from the 1x treatment rate as adequate and the characterization 

of residues from the 3x treatment rate as supplemental data.

In summary, the cotton metabolism study has now been upgraded to acceptable status based on 

Syngenta’s submission of the requested information pertaining to actual application rate for the 

higher treatment rate, the lighting and temperature conditions used in the greenhouse, the dates of 

sample analysis, quantitative data for the unknowns and nonextractable residues, and the 

designation of possible structures for Metabolites B-3 and C-1. The supplementary data indicate 

that following application of CF3-labeled fomesafen at 1x, approximately 61% TRR (0.040 ppm) 

resulted in extractable peaks (A-1, A-2, A-3, fomesafen, B, C, D) in cotton gin byproducts with 

the parent fomesafen comprising 11.6% TRR (0.008 ppm). Following application of NO2-

labeled fomesafen at 1x, approximately 55% TRR (0.024 ppm) resulted in extractable peaks 

(fomesafen, E, F, G) in cotton gin byproducts with fomesafen comprising 27.0% TRR (0.012 

ppm).
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Figure 1. Proposed Structure and MS/MS Product Ion Assignments for Metabolite B-3 in Cotton Gin 

Byproducts.

(Note: figure was copied directly from MRID 47761905.)
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Figure 2. Proposed Structure and MS/MS Product Ion Assignments for Metabolite C-1 in Cotton Gin 

Byproducts.

(Note: figure was copied directly from MRID 47761905.)
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Potato

When a pesticide will be used on several different crops the Agency requires plant metabolism 

studies on three diverse crops. Currently adequate tomato, soybean, and cotton metabolism 

studies are available for fomesafen. The HED Chemistry Science Advisory Council (ChemSAC) 

specifically considered the need for metabolism studies for fomesafen in a meeting on 7/25/2007. 

According to the 07/25/2007 minutes, the ChemSAC specifically recommended submission of a 

root/tuber metabolism study because cotton and soybeans are considered similar within the 

Agency and internationally (e.g., OECD). Given this fact, ChemSAC concluded that a potato 

metabolism study would still be required. A potato metabolism study, in which both the root and 

tops/foliage are analyzed, is required to support the proposed use on potatoes. HED cannot 

recommend for a tolerance in/on potatoes until an adequate potato metabolism study is 

submitted.

860.1300 Nature of the Residue - Livestock

MRID 00110508 (PP#2G2745, 1/28/83, A. Rathman, and PP#4F2997, 9/25/94, A. Smith)

MRID 00135635 (PP#4F2997, 9/25/84, A. Smith)

Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis

Syngenta submitted a goat metabolism study in conjunction with the temporary tolerance petition 

for soybeans (PP#2G2745). A single goat was dosed with [nitrophenyl14C]fomesafen at 0.1 

ppm in the diet for 7 days; the goat was sacrificed 16 hours after the final dose. The dosing level 

corresponds to ~2x and 5x the maximum theoretical dietary burdens to beef and dairy cattle, 

respectively. TRR reached a maximum in milk of 0.0008 ppm on Day 3. TRR were 0.003 ppm 

in liver, 0.004 ppm in kidney, <0.003 ppm in meat, and <0.005 ppm in fat. Approximately 70% 

of the dosed radioactivity was excreted. No residue characterization was conducted because of 

low radioactivity levels. 

A goat metabolism study was reviewed in conjunction with the soybean permanent tolerance 

petition (PP#4F2997). A single goat was dosed with [nitrophenyl14C]fomesafen at 10.3 ppm in 

the diet for 3 consecutive days; the goat was sacrificed 4 hours after the final dose. The dosing 

level corresponds to ~184x and 468x the maximum theoretical dietary burdens to beef and dairy

cattle, respectively. TRR were 0.20 ppm in liver, 0.28 ppm in kidney, 0.009 ppm in meat, 0.006 

ppm in fat, and 0.014 ppm in milk. Approximately 47% of the dosed radioactivity was excreted. 

Fomesafen was not found in any milk, tissue, or excreta sample. The identified metabolites were 

5-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-N-methylsulfonylanthranilamide (compound XV) and 5-

(2-chloro-α,α,α-trifluoro-p-tolyloxy) anthranilic acid (compound V). Compound XV was found 

at 10% TRR in liver and 20.9% TRR in kidney, and compound V was found at 34.5% TRR in 

liver and 33.9% TRR in kidney. 

Conclusions. The available livestock metabolism data are adequate to satisfy data requirements. 

The significant components of the animal residues are fomesafen and its metabolites 5-(2-chloroα,α,α-trifluoro-p-tolyloxy) anthranilic acid (compound V) and 5-(2-chloro-α,α,α-trifluoro-ptolyloxy)-N-methylsulfonylanthranilamide (compound XV). 
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Based on the residue levels in goat matrices following dosing at to ~184x and 468x the 

maximum theoretical dietary burdens to beef and dairy cattle, respectively, HED concludes that 

the proposed/registered uses of fomesafen on cotton, dry and snap beans, soybeans, potatoes, and 

tomatoes result in a 40 CFR §180.6(a)(3) situation for livestock commodities; i.e., there is no 

reasonable expectation of finite residues in livestock commodities. There are no poultry and 

swine feedstuffs associated with the proposed uses.

860.1340 Residue Analytical Methods

MRID 40007101 (Enforcement method for soybean; PP#4F2997, CB No. 2253, 8/18/87, W. Chin)

MRIDs 44754703 and 44754704 (Enforcement method for cotton; DP# 325801, 4/25/06, D. Davis)

MRIDs 45093602 and 45093603 (Revised enforcement method for soybean; DP# 325801, 4/25/06, D. Davis)

Plant commodities

Enforcement methods

Three residue analytical methods have been submitted to the Agency for the purpose of tolerance 

enforcement. All of these methods quantitate residues of fomesafen in/on crop commodities and 

are briefly described below.

(i) The HPLC/UV method, GAM-RM-001/86, was submitted in the initial soybean petition 

(PP#4F2997). The method, entitled “The Determination of PP021 in Soybeans - A High 

Performance Liquid Chromatography Method”, involves the extraction of residues in crop 

samples with acetonitrile:concentrated HCl (98:2, v:v). The extract is diluted with water and 

partitioned with hexane. The aqueous phase is partitioned with dichloromethane (DCM), and the 

DCM phase is cleaned up by ion-exchange chromatography on an amino column for HPLC 

analysis using a C18 column and UV detection at 290 nm. The limit of quantitation (LOQ)

reported in the method is 0.01-0.02 ppm. The method has successfully passed an Agency

tolerance method validation.

(ii) The GC/NPD method, TMR0836B, was submitted and reviewed in DP# 325801 to replace 

the existing HPLC/UV method for soybean commodities. The method is entitled “Determination 

of Fomesafen in Soybeans by Gas Chromatography with Nitrogen/Phosphorus Detection.” The 

new method differs from the existing enforcement method in the use of GC/NPD for analysis of 

extracts. The extraction procedures of the method are similar to those of the existing HPLC/UV 

method; however, in the new method, fomesafen is converted to its methylated analog to allow 

GC determination. Briefly, residues in/on soybean forage, hay, and seed samples are extracted 

with acidified ACN, and the extract is acidified and partitioned with hexanes. The resulting 

aqueous phase is partitioned with DCM, and the DCM phase is redissolved in methyl isobutyl 

ketone (MIBK). The MIBK solution is mixed with iodomethane and then heated to methylate 

fomesafen. The methylated residues are cleaned up on a silica gel column for GC/NPD analysis. 

Results are reported in terms of fomesafen. The validated LOQ reported in the method is 0.02 

ppm for soybean forage, hay, and seed. A limit of detection (LOD) was not reported; Syngenta 

estimated the LOD to be less than 10-20% of the LOQ in these commodities. 

(iii) A GC/NPD method (TMR0800B) was submitted in the cotton petition (PP#9F5068) and 

reviewed in DP# 325801. The method is entitled “Determination of Fomesafen in Cottonseed 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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and Gin Trash by Gas Chromatography.” Using this method, residues in cotton matrices are 

extracted with acidified ACN, and the extract is partitioned with hexanes. The resulting aqueous 

phase is partitioned with DCM, and the DCM phase is redissolved in MIBK. The MIBK solution 

is mixed with iodomethane and then heated to methylate fomesafen. The methylated residues are 

cleaned up on a silica gel column for GC/NPD analysis. Results are reported in terms of 

fomesafen per se. The validated LOQ reported in the method is 0.02 ppm for cotton seed and gin 

byproducts. An LOD was not reported; Syngenta estimated the LOD to be less than 10-20% of

the LOQ in cotton seed and gin byproducts.

HED’s review (DP# 325801, 4/25/06, D. Davis) of GC/NPD Methods TMR0836B (soybeans) 

and TMR0800B (cotton) required the submission of additional data before the methods can be 

deemed suitable for tolerance enforcements. The Agency required confirmatory raw data, the 

modification of the method to incorporate extraction and analysis of specific crop commodities, 

and the submission of confirmatory methods. 

Syngenta’s Response to Analytical Method Data Gaps as a Condition of Registration

Reference List: 47761905 (No DER generated)

47761903.der.doc (Includes MRID 47761904)

Syngenta has submitted MRID 47761905 which provides responses to the information and data 

requested by the Agency. For purposes of clarity, the specific deficiencies pertaining to residue 

analytical methods are re-stated below followed by the petitioner’s response as well as HED’s 

comments regarding the adequacy of response.

Deficiency: “Syngenta must submit raw data to support the method validation data reported in 

MRIDs 44754703, 45093602, 45093603, 45268502 and 45268503.”

Syngenta’s response: Syngenta has been unable to locate the method validation raw data as 

requested. In the absence of these raw data, Syngenta undertook additional work to confirm the 

validity of the method extraction procedure specified in the MRID numbers cited above. 

Specifically, soybean and cotton commodities, as well as dry beans, were analyzed using an 

updated method, GRM045.01A. This method utilizes the same extraction procedure as the 

previous methods. This method did differ from the previous methods by the inclusion of a SPE 

clean-up step, and the analysis was conducted using LC/MS/MS. These results are reported in 

MRIDs 47761903 and 47761904. 

HED’s comments/conclusions: 

Syngenta Crop Protection has submitted descriptions and validation data for a new proposed 

enforcement method, Method GRM045.01A, which is entitled “Fomesafen Analytical Method 

for the Determination of Residues of Fomesafen in Crop Commodities by LC-MS/MS.” This 

high performance liquid chromatography with tandem mass spectrometry detection (LC/MS/MS) 

method is based on previously submitted gas chromatography with nitrogen phosphorus 

detection (GC/NPD) methods (refer to DP# 325801, D. Davis, 4/25/06) developed by Zeneca 

AG.

Method GRM045.01A uses extraction procedures modified from the previous GC/NPD methods. 

In the revised method, fomesafen residues are extracted with 1% hydrochloric acid in 
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acetonitrile. An aliquot is subjected to an SPE cleanup and analyzed using LC/MS/MS. A 

second ion transition may be monitored for confirmation. The LOQ is 0.02 ppm for fomesafen 

in each matrix. Representative spectra and linearity data were submitted demonstrating adequate 

sensitivity.

No independent laboratory validation (ILV) or radiovalidation data have been submitted for 

Method GRM045.01A. Because the method is an improvement on the previously established 

GC/NPD methods, these data will not be required. HED will also not request ACB/BEAD for a 

tolerance method validation, and will forward the method to FDA for inclusion in the Pesticide 

Analytical Manual (PAM) Volume II as an enforcement method. This deficiency is resolved.

Deficiency: “Syngenta should modify GC/NPD Method No. TMR0836B to include instructions 

for the extraction and analysis of dry bean, snap bean, and aspirated grain fractions. The 

modified method should then be forwarded to FDA for inclusion in the Pesticide Analytical 

Manual (PAM) Volume II.”

Syngenta’s response: The new analytical method GRM045.01A meets this requirement.

HED’s comments/conclusions: LC/MS/MS method (GRM045.01A) is written to include 

analysis of a wider variety of commodities (including snap beans, dry beans, and soybean 

aspirated grain fractions) for residues of fomesafen; special instructions are included in the 

analytical procedures for separate extraction of residues in crop commodities except for oil and 

for oil samples. This deficiency is resolved.

Deficiency: “Syngenta must propose alternative confirmatory methods for the proposed new 

enforcement methods. The currently proposed confirmatory methods involve substitution of 

columns with only slight polarity differences and likely very similar elution times and are not 

considered sufficient for confirmation of an enforcement method.”

Syngenta’s response: The new analytical method, (GRM045.01A), which incorporates the 

highly specific LC/MS/MS detection, satisfies this requirement.

HED’s comments/conclusions: The new analytical method, (GRM045.01A) includes a second 

transition for confirmatory analysis. The ion transition monitored for fomesafen is m/z 

437→195; the ion transition m/z 437→222 is available as a confirmation.

In summary, Syngenta has submitted a new LC/MS/MS method (GRM045.01A) for analysis of 

fomesafen residues in crop commodities. This method is the updated version for previous 

Zeneca AG data-gathering methods (TMR08055B, TMR0879B, TMR0800B, and TMR0881B). 

The method uses extraction procedures as previously described in the above-mentioned methods, 

SPE cleanup procedures, and the final determination step by LC/MS/MS technology for analysis 

of fomesafen residues. The validated LOQ of the method is 0.02 ppm. Method GRM045.01A

has been adequately validated at fortification levels of 0.02 ppm and 0.2 ppm in snap beans, pinto

beans (dry bean), corn oil, cotton, undelinted seed and gin byproducts, and soybean forage, hay, 

and aspirated grain fractions.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 26 of 44

No radiovalidation data have been submitted for LC/MS/MS method (GRM045.01A); however, 

because the extraction procedures of the method are similar to those of the soybean metabolism 

study, radiovalidation data are not needed. Since LC/MS/MS method (GRM045.01A) appears to 

be a superior method to the previously submitted methods for fomesafen due to its state of the art 

technology and its specificity, HED will not require independent laboratory validation data. 

HED will also not request ACB/BEAD for a TMV and will forward the method to FDA for 

inclusion in the Pesticide Analytical Manual (PAM) Volume II as an enforcement method.

Data-collection methods

Samples of raw and processed commodities of potatoes and tomatoes, which were collected from 

the magnitude of the residue studies, were analyzed for residues of fomesafen using a high 

performance liquid chromatography method with tandem mass spectrometry detection based on 

an HPLC/UV method (GAM-RM-001/86). The method was adequately validated during 

concurrent analysis of samples. The lowest level of method of validation (LLMV) was 0.025 

ppm for each matrix.

Livestock commodities

Because there are no established or proposed tolerances for livestock commodities, an 

enforcement method for livestock commodities is not required.

860.1360 Multiresidue Methods

DER Reference List: 47761901.der.doc

Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis

HED (DP# 325801) previously required the submission of multiresidue method testing data for 

fomesafen. In response, the petitioner submitted MRID 47761901. The submission has been 

reviewed by HED, and the Executive Summary of the study DER is reproduced below.

Syngenta Crop Protection has submitted multiresidue testing data for fomesafen (free acid) 

following testing and analysis according to FDA Multiresidue Test Guidelines in PAM Vol. I

(1/94). The Decision Tree for MRM Testing found in the Multiresidue Protocols was followed 

in determining the response patterns. Fomesafen (free acid) was tested through Protocols A, B, 

and C. Protocols D, E, and F were not tested as no residues were detected using Protocol C. The 

compound was not tested under Protocol G because it is not a substituted urea.

 

Fomesafen does not have an N-methylcarbamate structure and did not produce a response on the 

fluorescence detector under Protocol A. In Protocol B testing, methylated fomesafen was not 

recovered from Florisil; therefore, no additional work was performed under Protocol B.

Fomesafen (free acid) did not produce a response under Protocol C, using gas chromatography

with either the nitrogen phosphorus or the electron capture detector (GC/NPD or GC/ECD). 

Therefore, it was not tested using Protocol D, E, or F.

Conclusions: These data indicate that FDA multiresidue methods are not suitable for 

determining residues of fomesafen. The submitted data will be forwarded to U.S. FDA for 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 27 of 44

further evaluation.

860.1380 Storage Stability

DER Reference: 47761902.der.doc (corn, soybean, cotton, and wheat matrices storage stability data)

DER Reference: 47473903.de1.doc (potato tuber concurrent storage stability data)

DER Reference: 47473903.de2.doc (potato processed commodities concurrent storage stability data)

DER Reference: 47473902.de1.doc (tomato fruit concurrent storage stability data)

DER Reference: 47473902.de2.doc (tomato processed commodities concurrent storage stability data)

Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis

Sample storage duration and conditions 

The storage durations and conditions of potato and tomato samples from the submitted 

magnitude of the residue and processing studies are presented in Table 5. Table 5 also includes 

the storage conditions and durations of samples from the crop field trial, processing, and field 

rotational crop studies which were submitted to support previous petitions (PP#s 1E6228, 

9F5068, and 6E4653).

Table 5. Summary of Storage Conditions and Durations of Samples from Crop Field Trial, Processing, and

Field Rotational Crop Studies. 

Matrix Storage 

Temperature (°C)

Actual Storage 

Duration

Interval of Demonstrated Storage Stability

Samples from Previous Petitions (PP#s 1E6228, 9F5068, and 6E4653)

reviewed under DP# 325801, 4/25/06, D. Davis

Cotton Field Trials (MRID 44754701)

Cotton gin 

byproducts

~-18 232-324 days

(7.6-10.7 months)

Storage stability data indicate that residues of 

fomesafen appear to be erratic in/on cotton gin

byproducts, but overall show general stability; 

corrected stored recoveries were 69% at 2.5 

months, 80% at 3.2 months, 142% at 8.8 

months, and 68% at 14.6 months.

Soybean Processing Study (MRID 45093601)

Soybean hulls -20 294 days

(9.7 months)

Storage stability data indicate that residues of 

fomesafen appear to be relatively stable in/on 

soybean hulls stored frozen at -31 to -3 oC for 

up to ~15 months.

Soybean refined oil 288 days

(9.5 months)

Storage stability data indicate that residues of 

fomesafen appear to be relatively stable in/on 

soybean oil for up to ~9 months but increased 

to a recovery of 149% by ~15 months.

Field Rotational Crop Study (MRID 00158936)1

Corn forage -20 235-272 days

(7.7-8.9 months)

Storage stability data indicate that residues of 

fomesafen appear to be relatively stable in/on 

corn K+CWHR, forage, and stover, and wheat 

forage and straw stored frozen at -31 to -3 oC 

for up to ~15 months.

Corn cob 178-223 days

(5.8-7.3 months)

Corn fodder 178-223 days

(5.8-7.3 months)

Wheat forage 361-388 days

(11.9-12.7 months)
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Table 5. Summary of Storage Conditions and Durations of Samples from Crop Field Trial, Processing, and

Field Rotational Crop Studies. 

Matrix Storage 

Temperature (°C)

Actual Storage 

Duration

Interval of Demonstrated Storage Stability

Wheat straw 289-339 days

(9.5-11.1 months)

Field Rotational Crop Study (MRID 45268501)

Field corn, forage <-10 280-316 days

(9.2-10.4 months)

Storage stability data indicate that residues of 

fomesafen appear to be relatively stable in/on 

corn forage and stover, and wheat forage and 

straw stored frozen at -31 to -3 oC for up to 

~15 months.

Field corn, stover 239-279 days

(7.9-9.2 months)

Sorghum, forage 232-289 days

(7.6-9.5 months)

Sorghum, stover 182-273 days

(6.0-9.0 months)

Samples from Current Petition (PP#9F7563)

Potato Field Trials and Processing Study (MRID 47473903)

Potato tuber -40 to -6 316-399 days

(10.4-13.1 months)

Concurrent storage stability data indicate that 

residues of fomesafen appear to be relatively 

stable for up to 420 days in/on frozen potato 

tuber, 311 days in potato flakes, 308 days in 

potato chips, and 307 days in wet potato peel. 

Potato, tuber (RAC) -40 to -6 308 days

(10.1 months)

Potato, flakes 299 days

(9.8 months)

Potato, chips 298 days

(9.8 months)

Potato, wet peel 293 days

(9.6 months)

Tomato Field Trials and Processing Study (MRID 47473902)

Tomato fruit -40 to -5 211-302 days

(6.9-9.9 months)

Concurrent storage stability data indicate that 

residues of fomesafen appear to be relatively 

stable for up to 319 days in/on tomato fruit

and 236 days in tomato paste and puree.

Tomato, fruit (RAC) -40 to -5 241 days

(7.9 months)

Tomato, paste 229 days

(7.5 months)

Tomato, puree 229 days

(7.5 months)

1

 For the field rotational crop study reported in MRID 00158936, the dates of sample analysis were not provided. 

The maximum storage interval for each sample, based on the study completion date, was calculated by the study 

reviewer.

Storage stability data

Storage stability data were concurrently generated with the potato/tomato field and processing 

studies. For each crop, control samples of the respective matrices were fortified with fomesafen 

at ~0.25 ppm and placed in storage under the same frozen conditions as the treated samples. No 

zero-day analyses were conducted on the fortified samples placed into storage. Rather, triplicate 

stored samples were analyzed along with a control sample and freshly fortified samples at an 

interval reflecting the maximum storage intervals from the field and processing studies. Average 

corrected recovery ranges of fomesafen were: 78-90% in potato tubers after 420 days, 79-99% in 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 29 of 44

potato flakes after 311 days, 72-77% in potato chips after 308 days, 71-81% in potato wet peel 

after 307 days, 81-92% in tomato fruits after 319 days, 89-108% in tomato paste after 236 days, 

and 87-109% in tomato puree after 236 days. Although no 0-day analysis was conducted, the 

data indicate that fomesafen is stable under frozen storage conditions at the maximum intervals

tested. These data indicate that no corrections of residues need to be applied to the study results.

Syngenta’s Response to Storage Stability Data Gaps as a Condition of Registration

HED previously requested additional storage stability data to support the storage conditions and 

intervals of samples collected from various field and rotational crop studies (DP# 325801, 

4/25/2006, D. Davis). The specific deficiency is re-stated below followed by the petitioner’s 

response and HED’s comments regarding the adequacy of response.

Deficiency: Data are required depicting the stability of residues of fomesafen in/on the following 

commodities: cotton gin byproducts stored frozen for up to 11 months; soybean hulls and oil 

stored frozen for up to 10 months; corn cob stored frozen for up to 7 months; wheat forage and 

straw during frozen storage for up to 13 months; and field corn or sorghum forage and stover 

during frozen storage for up to 10 months.

Syngenta’s response: The requested storage stability data have been developed and are reported 

in MRID 47761902. This interim report included stability data through 13 months as required 

but the study will continue with planned analysis at both 18 and 24 months. Upon completion of 

the analysis of the 24 month samples, the final report will be submitted. HED has reviewed the 

study submission; the Executive Summary of the completed study DER is presented below. 

HED’s comments/conclusions: Syngenta Crop Protection has submitted interim storage stability

data for fomesafen in corn kernel plus cob with husks removed (K+CWHR), forage, and stover; 

cotton gin byproducts; soybean hulls and oil; and wheat forage and straw. These data were 

submitted in response to data gaps for fomesafen storage stability data to support use of the 

sodium salt on these crops (DP# 325801, D. Davis, 4/25/06).

Samples of eight commodities (corn K+CWHR, forage, and stover; cotton gin byproducts; 

soybean hulls and oil; and wheat forage and straw) were spiked with fomesafen at 1.00 ppm.

Fortified and unfortified samples were stored at -31 to -3 °C. The petitioner reports that samples 

of each commodity were analyzed after 0, 1, 3, 6, and 13 months of storage, with planned 

additional intervals of 18 and 24 months; however, inspection of the fortification and analysis 

dates provided in MRID 47761902 yield different intervals. The study was conducted by

ADPEN Laboratories, Inc. (Jacksonville, FL).

Crop samples were analyzed using Syngenta method GRM045.01B. The extraction and analysis 

procedures for this method are similar to those of method GRM045.01A. The validated LOQ is 

0.02 ppm for fomesafen in each crop matrix.

Residues of fomesafen appear to be relatively stable in/on corn K+CWHR, forage, and stover, 

soybean oil and hulls, and wheat forage and straw stored frozen at -31 to -3 oC for up to ~15 

months. Residues of fomesafen appear to be erratic in/on cotton gin byproducts, but overall 

show general stability. An adequately validated method was used for the quantitation of 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 30 of 44

fomesafen in the crop matrices tested in the storage stability study.

The interim storage stability data adequately support the storage conditions and intervals of crop 

commodity samples discussed in DP# 325801. In the interim report, the petitioner reported that 

samples of each commodity were analyzed after 0, 1, 3, 6, and 13 months of storage, with 

planned additional intervals of 18 and 24 months. When actual storage intervals were 

recalculated using dates from the raw data, samples were extracted after 0, 1.1-2.5, 3.2-4.0, 8.2-

9.2, and 14.6-15.0 months. It appears from the raw data that samples from the 0-, 1-, and 3-

month storage intervals were fortified at later dates than samples from the 6- and 13-month 

storage intervals. The petitioner must explain in the final report why the fortification times are 

different and why the actual storage intervals differ so greatly from the nominal storage intervals.

860.1400 Water, Fish, and Irrigated Crops

There are no proposed uses that are relevant to this guideline topic.

860.1460 Food Handling

There are no proposed uses that are relevant to this guideline topic.

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with the proposed use on tomatoes. Although, there 

are ruminant livestock feedstuffs associated with the petition on potatoes, they are not addressed 

in this review, due to the lack of a root/tuber metabolism study. A ruminant feeding study was 

not submitted and is not needed for the purpose of this petition. HED concludes that the 

registered uses of fomesafen on cotton, dry and snap beans, and soybean and the proposed use of 

fomesafen on potato result in a 40 CFR §180.6(a)(3) situation for livestock commodities; there is 

no reasonable expectation of finite residues in livestock. Therefore, no livestock feeding studies 

are required to support the proposed/registered uses of fomesafen sodium. Syngenta should note 

that if additional uses are proposed in the future which result in an increase in the dietary burden, 

livestock feeding studies may be required.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 31 of 44

860.1500 Crop Field Trials

DER Reference List 47473903.de1 (Potato)

47473902.de1 (Tomato)

A summary of the reviewed crop field trial data for potato and tomato is presented in Table 6.

Table 6. Summary of Residue Data from Crop Field Trials with Fomesafen.

Commodity Total Applic. 

Rate

(lb ae/A)

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 Median

(STMdR)

Mean

(STMR)

Std. Dev.

Potato

(Proposed use = One preemergence application after planting but before crop emergence at 0.25 lb ae/A; 

70-day PHI)

Potato tubers 0.237-0.263 70-141 26 <0.025 <0.025 <0.025 0.025 0.025 ---

Tomato

(Proposed use = One preplant non-incorporated preemergence application up to 7 days prior to transplanting of 

tomatoes at 0.375 lb ae/A; 70 day PHI)

Tomato fruit 0.373-0.399 71-104 24 <0.025 <0.025 <0.025 0.025 0.025 --

1

 HAFT = Highest Average Field Trial.

Potato

Syngenta Crop Protection has submitted field trial data for fomesafen on potatoes. Thirteen trials 

were conducted in the United States in Zones 1 (NY; 1 trial), 2 (MD, NC and NJ; 3 trials), 3 (FL; 

1 trial), 5 (MI and WI; 2 trials), 8 (CO; 2 trials), and 11 (ID and WA; 4 trials) during the 2006

growing season. 

At each test location, a single preemergence application of Reflex® Herbicide (EPA Reg. No. 

100-993) was made to potatoes at 0.237 to 0.263 lb ae (acid equivalents)/A. Reflex® Herbicide 

is a soluble concentrate liquid formulation containing 22.8% sodium salt of fomesafen as the 

active ingredient (equivalent to 2 lb ae/gal of fomesafen). Applications were made using ground 

equipment in spray volumes of 16-36 gal/A without an adjuvant. Samples of mature potatoes 

were collected at a PHI of 70-141 days. Additional samples were collected from one trial to 

conduct a processed food and feed study; refer to the 860.1520 DER for MRID 47473903 for the 

study details and results.

Samples of potatoes were analyzed for residues of fomesafen using a LC/MS/MS method based 

on an HPLC/UV method (GAM-RM-001/86), entitled “The Determination of PP021 in Soybeans 

– A High Performance Liquid Chromatographic Method,” which is an enforcement method for 

fomesafen. The method was adequate for data collection based on adequate concurrent recovery

data. The LLMV was 0.025 ppm for potato.

The maximum storage duration of potatoes from harvest to analysis was 399 days (13.1 months) 

for analysis of fomesafen. Sample storage conditions and durations are supported by concurrent 

storage stability data. However, zero-day data were not provided with the storage stability study. 

The petitioner is reminded that storage stability studies should always include a zero-day

sampling interval to ensure that the samples were fortified properly [see OPPTS 

860.1380(d)(6)(i)].
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 32 of 44

Residues of fomesafen were less than the LLMV (<0.025 ppm) in/on potatoes harvested 70-141 

days following a single pre-emergence application of the 2 lb ae/gal SL formulation of fomesafen 

at a total rate of 0.237-0.263 lb ae/A.

Tomato

Syngenta Crop Protection has submitted field trial data for fomesafen on tomatoes. Twelve trials 

were conducted in the United States in Zones 1 (NY; 1 trial), 2 (NC; 1 trial), 3 (FL; 2 trials); 10 

(CA and NM; 8 trials) during the 2006 growing season. 

At each test location, a single pre-transplant application of Reflex® Herbicide (EPA Reg. No. 

100-993) was made to tomatoes at 0.373 to 0.399 lb ae/A. Reflex® Herbicide is a SL

formulation containing 22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 

lb ae/gal of fomesafen). Applications were made using ground equipment in spray volumes of 

21-35 gal/A without an adjuvant. Samples of mature tomatoes were collected at a PHI of 71-104 

days. Additional samples were collected from one trial to conduct a processed food and feed 

study; refer to the 860.1520 DER for MRID 47473902 for the study details and results.

Samples of tomatoes were analyzed for residues of fomesafen using a high performance liquid 

chromatography method with tandem mass spectrometry detection (LC/MS/MS) based on an 

HPLC/UV method (GAM-RM-001/86), entitled “The Determination of PP021 in Soybeans – A 

High Performance Liquid Chromatographic Method,” which is an enforcement method for 

fomesafen. The method was adequate for data collection based on adequate concurrent recovery

data. The lowest level of method of validation (LLMV) was 0.025 ppm for tomato.

The maximum storage duration of tomatoes from harvest to analysis was 302 days (9.9 months)

for analysis of fomesafen. Sample storage conditions and durations are supported by concurrent 

storage stability data. However, zero-day data were not provided with the storage stability study. 

The petitioner is reminded that storage stability studies should always include a zero-day

sampling interval to ensure that the samples were fortified properly [see OPPTS 

860.1380(d)(6)(i)].

Residues of fomesafen were less than the LLMV (<0.025 ppm) in/on tomatoes harvested 71-104 

days following a single pre-transplant application of the 2 lb ae/gal SL formulation of fomesafen 

at a total rate of 0.373-0.399 lb ae/A.

Conclusions. The submitted field trial data for fomesafen on tomatoes are acceptable and 

support the proposed uses. An adequate number of trials were conducted in the appropriate 

geographic regions at ~1x the maximum proposed rate using Reflex® Herbicide, and the 

appropriate samples were collected from each test around the proposed PHI. All treated samples 

bore residues below the LLMV (<0.025 ppm). Based on these data, HED recommends a 

tolerance of 0.025 ppm for residues of fomesafen in/on tomatoes.

The submitted field trials for potatoes may be adequate, pending outcome of the required 

metabolism study. An adequate number of trials were conducted in the appropriate geographic 

regions at ~1x the maximum proposed rate using Reflex® Herbicide, and the appropriate 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 33 of 44

samples were collected from each test around the proposed PHI. A potato metabolism study is 

outstanding, as described in section 860.1300 above. If the new study does not identify any

additional residues of concern, then the field trial data are adequate. However, if additional 

residues of concern are found, then a full set of field trials reflecting analysis of the additional 

residues will be required.

Syngenta’s Response to Cotton Field Trial Data Gaps as a Condition of Registration

Reference List: 47761905 (No DER generated)

HED previously reviewed (DP# 325801, 4/25/2006, D. Davis) a magnitude of the residue study

on cotton (MRID 44754701) submitted by Syngenta in support of a cotton tolerance petition 

(PP#9F5068). Although the study was deemed unacceptable to fulfill data requirements, HED 

concluded that the cotton study may be upgraded pending submission of additional information 

pertaining to the conduct and other experimental details. In response, Syngenta has submitted 

MRID 47761905 which provides responses to the information requested. The specific 

deficiencies are re-stated below followed by the petitioner’s response and HED’s comments 

regarding the adequacy of response.

Deficiencies: “The available crop field trial data are adequate to support the proposed use on 

cotton provided the following data are provided:

· A summary of weather conditions at the individual sites, indication as to whether 

irrigation was used, and average historical data for temperature and rainfall for the 

duration of the field intervals of the trials. 

· Soil characteristics data (percent organic matter, pH, and cation exchange 

capacity) for the individual sites.

· Raw data including at least: (i) field notes and/or reports on application 

(including which spray adjuvant was used), plot maintenance, and sample harvest; 

(ii) calibration of application equipment (for confirmation of application rate); and 

(iii) a specific description (which may be in the field notes) as to how and where 

(within the plot) the sample was taken and what was done to ensure that samples 

were representative of the test plot.”

Syngenta’s response: Raw data from the previously reviewed cotton field trials were attached in 

Appendix 2 of MRID 47761905. The raw data provided specific details on the application, plot 

maintenance, and sample harvest. The raw data confirm the conditions reported in the initial 

report. The calibration of application equipment (for confirmation of application rate) and 

weather conditions (NOAA Climatological Data) were also provided in these reports. At each 

trial location, information pertaining to the soil type, percent organic matter, pH and cation 

exchange capacity were provided from the Soil Survey Geographic (SSURGO) Database. 

HED’s comments/conclusions to deficiencies: The available cotton field trial data have now 

been upgraded to acceptable status based on Syngenta’s submission of the requested information 

pertaining to field weather conditions, soil characteristics, raw data of field notes, calibration of 

equipment, and sampling procedures that were employed in the conduct of the cotton trials. The 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 34 of 44

Agency concludes that adequate residue data are available to support the established tolerances of

0.025 ppm each for cotton gin byproducts and undelinted cottonseed. This deficiency is 

resolved.

860.1520 Processed Food and Feed

DER Reference List 47473903.de2 (Potato)

47473902.de2 (Tomato)

The observed processing factors reported for potatoes and tomatoes, resulting from treatment at 

1x, are presented in Table 7.

Table 7. Summary of Observed Processing Factors for Fomesafen in Potatoes and Tomatoes Following 

Treatment at 1x.

RAC Processed Commodity Processing Factor

Potato, tuber Flakes NC

1

Chips NC

Wet peel NC

Tomato, fruit Paste NC

Puree NC

1

 NC = Not calculated. The processing factor could not be calculated because residues were below the LLMV (<0.025 ppm) in 

both the RAC and the processed fractions.

Potato

Syngenta Crop Protection submitted magnitude of the residue data for fomesafen on the 

processed commodities of potatoes. Samples used for processing were generated from one 

potato field trial conducted in ID (Zone 11) during the 2006 growing season. The test 

formulation used in the trial was Reflex® Herbicide (EPA Reg. No. 100-993), a SL formulation

containing 22.8% sodium salt of fomesafen as the active ingredient (equivalent to 2 lb ae/gal of 

fomesafen). Potatoes were harvested 130 days following a single preemergence application of a 

2 lb ae/gal SL formulation of fomesafen at 0.256 lb ae/A (~1x field application rate). 

Application was made using ground equipment in a spray volume of 20 gal/A without an 

adjuvant. The potatoes were processed into potato flakes, chips and wet peel.

Samples of potatoes and potato processed commodities were analyzed for residues of fomesafen 

using a high performance liquid chromatography method with tandem mass spectrometry

detection (LC/MS/MS) based on an HPLC/UV method (GAM-RM-001/86), entitled “The 

Determination of PP021 in Soybeans – A High Performance Liquid Chromatographic Method,” 

which is an enforcement method for fomesafen. The method was adequate for data collection 

based on adequate concurrent recovery data. The lowest level of method of validation (LLMV) 

was 0.025 ppm for potato tuber and processed commodities flakes, chips, and wet peel.

The maximum storage duration of the processing study samples were 308 days (10.1 months)

from harvest to analysis for potatoes (RAC) and 299 days (9.8 months), 298 days (9.8 months), 

and 293 days (9.6 months) from processing to analysis for potato flakes, chips and wet peel, 

respectively. Sample storage conditions and durations are supported by concurrent storage 

stability data. However, zero-day data were not provided with the storage stability study. The 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 35 of 44

petitioner is reminded that storage stability studies should always include a zero-day sampling 

interval to establish the residue levels present at the time samples are placed into storage [see 

OPPTS 860.1380(d)(6)(i)].

Residues of fomesafen were less than the LLMV (<0.025 ppm) in/on the potato tuber (RAC) and 

potato processed commodities. Therefore, concentration factors could not be calculated. The 

petitioner is reminded that samples used in processing studies should contain field-treated 

quantifiable residues so that concentration factors can be determined. Field treatment of the 

processing samples should have been done at exaggerated application rates to ensure that the 

samples were fortified properly [see OPPTS 860.1520(c)(2)].

According to Tables 2 and 3 of OPPTS 860.1520, the theoretical concentration factors for potato 

processed fractions are 4.0x for processed waste (wet peel) and 4.7x for flakes/granules.

Tomato

Syngenta Crop Protection submitted magnitude of the residue data for fomesafen on the 

processed commodities of tomatoes. Samples used for processing were generated from one 

tomato field trial conducted in CA (Zone 10) during the 2006 growing season. The test 

formulation used in the trial was Reflex® Herbicide (EPA Reg. No. 100-993), a soluble 

concentrate liquid (SL) formulation containing 22.8% sodium salt of fomesafen as the active 

ingredient (equivalent to 2 lb ae/gal of fomesafen). Tomatoes were harvested 104 days following 

a single pre-transplant application of a 2 lb ae/gal SL formulation of fomesafen at 0.380 lb ae/A

(~1x field application rate). Application was made using ground equipment in a spray volume of 

25 gal/A without an adjuvant. The tomatoes were processed into tomato paste and puree using 

standard commercial practices.

Samples of tomatoes and tomato processed commodities were analyzed for residues of 

fomesafen using a high performance liquid chromatography method with tandem mass 

spectrometry detection (LC/MS/MS) based on an HPLC/UV method (GAM-RM-001/86), 

entitled “The Determination of PP021 in Soybeans – A High Performance Liquid 

Chromatographic Method,” which is an enforcement method for fomesafen. The method was 

adequate for data collection based on adequate concurrent recovery data. The lowest level of 

method of validation (LLMV) was 0.025 ppm for tomato fruit, paste, and puree.

The maximum storage duration of the processing study samples were 241 days (7.9 months)

from harvest to analysis for tomatoes (RAC) and 229 days (7.5 months) from processing to 

analysis for tomato paste and puree. Sample storage conditions and durations are supported by

concurrent storage stability data. However, zero-day data were not provided with the storage 

stability study. The petitioner is reminded that storage stability studies should always include a 

zero-day sampling interval to ensure the samples were fortified properly [see OPPTS 

860.1380(d)(6)(i)].

Residues of fomesafen were less than the LLMV (<0.025 ppm) in/on the tomato fruit (RAC) and 

tomato processed commodities. Therefore, concentration factors could not be calculated. The 

petitioner is reminded that samples used in processing studies should contain field-treated 

quantifiable residues so that concentration factors can be determined. Field treatment of the 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 36 of 44

processing samples should have been done at exaggerated application rates to obtain sufficient 

residue levels for this processing study [see OPPTS 860.1520(c)(2)].

According to Table 2 of OPPTS 860.1520, the theoretical concentration factors are 5.5x for 

tomato paste and 1.4x for tomato puree.

Conclusions. The results of submitted potato and tomato processing studies show that residues 

of fomesafen were each below the LLMV (<0.025 ppm) in/on the respective RACs following 

application of Reflex® Herbicide at ~1x. Following processing of RACs bearing 

nonquantifiable residues, no measurable processing factors can be calculated because the 

processed commodities of potatoes and tomatoes also bore residues below the LLMV (<0.025 

ppm). The Agency would have preferred the use of exaggerated rates in the conduct of the 

processing studies to yield RACs with quantifiable residues; the registrant provided no 

justification for conducting the study at only a 1x rate. Since the proposed use is for 

preemergence/pre-transplant application and all RAC samples from the current potato and 

tomato field trials show residues below the LLMV and the residue data cover all significant 

growing regions for the crop requested as delineated in OPPTS 860.1500, for the purpose of this 

petition only, HED recommends a waiver for the conduct of new tomato processing studies at 

exaggerated rates.

The submitted processing study for potatoes may be adequate, pending outcome of the required 

metabolism study. A potato metabolism study is outstanding, as described in section 860.1300 

above. If the new study does not identify any additional residues of concern, then the processing 

study is adequate. However, if additional residues of concern are found, then a new processing 

study at exaggerated rates reflecting analysis of the additional residues will be required.

860.1650 Submittal of Analytical Reference Standards

Analytical standards for fomesafen are currently available in the EPA National Pesticide 

Standards Repository (personal communication with Dallas Wright, ACB, 9/22/09). The 

Repository has received from Syngenta new standards for fomesafen on 9/3/2009; the standard 

has an expiration date of 8/1/2012.

Analytical reference standards of fomesafen must be supplied and supplies replenished as 

requested by the Repository. The reference standards should be sent to the Analytical Chemistry

Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy Nguyen at 

the following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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860.1850 Confined Accumulation in Rotational Crops

Reference List: 47761905 (No DER generated)

Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis

HED previously concluded (DP# 325801, 4/25/2006, D. Davis) that the nature of the residue in 

rotational crops remains inadequately understood and requested a new study. In response, 

Syngenta has submitted MRID 47761905 which provides a narrative response to the data gap. 

The specific deficiency is re-stated below followed by the petitioner’s response and HED’s 

comments regarding the adequacy of response.

Deficiency: “If the registrant wishes to support a plant back interval <12 months, they must 

conduct a new confined rotational crop study. The study should reflect separate application of 

CP- and NP-label fomesafen at the maximum seasonal application rate to rotatable crops. The 

study should include the plantback intervals (PBIs) that Syngenta wishes to include on product 

labels, up to 12 months. For complete guidance on the conduct of the study, OPPTS GLN 

860.1850 should be conducted.”

Syngenta’s response: A confined rotational crop study is ongoing and will be completed by

12/31/2009.

HED’s comments/conclusions: The nature of the residue in rotational crops remains 

inadequately understood. Syngenta has previously been requested to conduct a new confined 

rotational crop study reflecting separate application of CP- and NP-label fomesafen at the 

maximum seasonal application rate to rotatable crops. According to Syngenta, a new confined 

rotational crop study is ongoing and will be completed by 12/31/2009.

860.1900 Field Accumulation in Rotational Crops

Reference List: 47761905 (No DER generated)

Residue Chemistry Memo DP# 325801, 4/25/06, D. Davis

HED previously summarized (DP# 325801, 4/25/2006, D. Davis) the available field 

accumulation data for fomesafen. The available data consisted of: (i) MRID 00110509 which 

was reviewed by the Environmental Fate and Effects Division (EFED) and was found to contain 

numerous deficiencies; (ii) MRID 00158936, a field rotational crop study on field corn and 

winter wheat; and (iii) MRID 45268501, a field rotational crop study on field corn and safened 

sorghum. HED concluded that the adequacy of these data cannot be determined until the nature 

of fomesafen residues in rotational crops has been delineated. The cited HED review identified 

deficiencies from the submitted studies. In response, Syngenta has submitted MRID 47761905 

which provides responses to the data gap. The specific deficiency is re-stated below followed by

the petitioner’s response and HED’s comments regarding the adequacy of response.

Deficiency: “At such time as the registrant has resolved any issues and the nature of the residue 

in rotational crops is understood, if the registrant wishes to pursue a plant back interval <12 

months for wheat and corn the following method validation data must be provided to support 

submitted wheat and corn rotational crop data. Data demonstrating that recoveries of the internal 

standard are linear relative to recoveries of fomesafen are required and information on the timing 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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of sample fortification is required. Additionally, data to support the reported method limit of 

quantitation of 0.01 ppm are required, as is information on the identity of the matrices fortified in 

the method validation.”

Syngenta’s response: Crop samples collected from the field rotational crop study were analyzed 

for residues of fomesafen following ICI Plant Protection Division Residue Analytical Method 

(PPRAM) No. 66. Briefly, the prepared rotational crop samples were extracted by

homogenization with acetonitrile and then acidified with concentrated HCl. After filtration and 

the addition of water and hexane, fomesafen was partitioned into dichloromethane and the

residue taken up into chloroform. Co-extracted materials were removed by Fractosil adsorption

chromatography. Final quantification was by 19F-nuclear magnetic resonance spectroscopy

(NMR) with internal standardization. For example in study PP021B046, in Experimental Data 

Sheet Reference NCA/80/2, Internal Standard (R152748) at a concentration of 0.05 ppm was 

added to all the samples by the addition of 2.5 mL of a 1.0 μg/mL standards reference 554/7. 

External Standard (fomesafen reference standard) at concentrations of 0.05 ppm was added to the 

fortified recovery samples by the addition of 2.5 mL of a 1.0 μg/mL standard reference 507/3. 

Raw data indicate that fortification of external recoveries, spiked with the internal standard 

R152748 plus fomesafen reference standard took place prior to extraction. To support the 

reported LOQ of 0.01 ppm, the petitioner provided calculation of results and limit of 

determination/detection. Residues were calculated using simple proportion calculation: 

Response of sample (fomesafen) x Concentration of Internal Standard

Response of Internal Standard Response ratio of fomesafen to Internal Standard

The Response Ratio (RR) was calculated by running standards of equal concentration of 

fomesafen and Internal Standard and calculating the mean response. During each analytical run 

of the study samples, an assessment of the limit of determination (limit of detection) was 

calculated from the baseline noise over the entire scan. Where no peaks of fomesafen were 

detected, residues were quoted in the report as less than this calculated value.

Syngenta believes that an assessment of a theoretical LOQ may be made from the study data. 

The lowest fortification level in this study was 0.05 ppm. For example in EDS NCA/86/2, an 

untreated control sample was spiked with 0.05 ppm Internal Standard (R152748) + 0.05 ppm 

fomesafen reference standard. The mean measured baseline noise for the analytical run at the 

retention time of fomesafen was 8 mm (l0, 7.5, 7 mm). The measured peak height of fomesafen 

was 159.5 mm. The measured peak height of Internal Standard was 138 mm. Calculation of 

unknown sample with example peak height of 32 mm (x4 baseline noise): [32 ÷ 138] x [0.05 ÷ 

1.16] = 0.009995 ppm. Therefore, the LOQ when the analysis was performed using this method 

has been calculated at 0.01 ppm.

Data were also included to demonstrate that the recoveries of the internal standard are linear to 

the recoveries of fomesafen. An assessment was carried out as part of the validation of PPRAM 

112. Samples were fortified with varying levels of fomesafen (0.1-5.0 ppm) keeping the Internal 

Standard fortification at a constant 0.5 ppm. A calibration graph giving fomesafen fortification 

versus fomesafen Internal Standard peak heights was plotted. A straight line passing through the 

origin was produced demonstrating that the instrument response to fomesafen was linear relative 

to the response to the internal standard.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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Finally, in response to HED’s request to provide identity of the matrices fortified in the method 

validation, Syngenta provided a table detailing the procedural recoveries of the matrices tested. 

The recoveries presented in Table 8 were compiled by Syngenta from residue trials performed 

between 1980 and 1985 where residues of fomesafen were determined in crops following ICI

Plant Protection Division Residue Analytical Method (PPRAM No. 66). Procedural recoveries 

were carried out over expected residue levels for each matrix.

Table 8. Recoveries of Fomesafen Using PPRAM 066 Arising from Supervised Residue Trials.

(Note – table was copied directly from MRID 47761905).

HED’s comments/conclusions: Syngenta has adequately responded to HED’s concerns and 

comments regarding the analytical method (PPRAM No. 66) used for the analysis of fomesafen 

from a previously submitted field rotational crop study (MRID 00158936). Syngenta has 

provided detailed information/data concerning: (i) when the fortification of external recoveries 

were performed; (ii) data to support the reported LOQ of 0.01 ppm; (iii) data demonstrating that 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 40 of 44

recoveries of the internal standard are linear relative to recoveries of fomesafen; and (iv) 

information on the identity of matrices fortified to validate the method. This deficiency is 

resolved.

Deficiency: “Should HED determine that 2-chloro-4-trifluoromethyl phenol is a residue of 

concern in rotated crops, the following method validation data are required to support the 

submitted wheat and corn rotational crop data. Data to support the reported method limit of 

quantitation are required, as are data demonstrating that the method can extract weathered 

residues of 2-chloro-4-trifluoromethyl phenol from field samples.”

Syngenta’s response: To date, Syngenta is unaware of such a determination being made by the 

Agency.

HED’s comments/conclusions: The Agency will make a determination as to what are the 

residues of concern in rotational crops when the results of an ongoing confined rotational crop 

study are submitted.

At this time, data are not available to support rotation to other crops beyond those commodities 

that are currently registered and proposed as primary crops; therefore the registrant must revise 

the Reflex® Herbicide label to permit immediate replanting of soybeans, cotton, dry beans, snap 

beans, potatoes, and tomatoes only with a restriction that other crops can only be planted 12 

months after treatment or 18 months after treatment if based on phytotoxicity concerns.

860.1550 Proposed Tolerances/Tolerance Reassessments for Fomesafen

Tolerances for fomesafen residues are listed in 40 CFR §180.433. The tolerance expression is in 

terms of “sodium salt of fomesafen, 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-

(methylsulfonyl)-2-nitrobenzamide.” HED has determined that the residue of concern for 

tolerance expression is fomesafen. Therefore, the established tolerance expression should be 

revised to be expressed in terms of fomesafen, by removing the phrase “sodium salt of” from 40 

CFR §180.433(a). In accordance with the HED Interim Guidance on Tolerance Expressions 

(5/27/09, S. Knizner), the tolerance expression for fomesafen should be revised to state:

“Tolerances are established for residues of fomesafen, including its metabolites 

and degradates, in or on the commodities in the table below. Compliance with the 

tolerance levels specified below is to be determined by measuring only fomesafen 

[5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide].”

HED cannot recommend for the requested tolerance in/on potatoes due to the lack of an adequate 

root/tuber metabolism study.

The available crop field trial data and revised analytical method will support the proposed 

tolerance of 0.025 ppm for tomato. As all residues were below the LLMV (<0.025 ppm) in/on 

RAC samples treated at 1x, the Agency’s tolerance spreadsheet was not used for determining the 

recommended tolerances. The petitioner’s draft label for Reflex® Herbicide reflects regional use 

of fomesafen on tomatoes. However, the residue chemistry data submitted in support of this 
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 41 of 44

action are of sufficient geographic representation to support full U.S. registration; therefore, HED 

recommends that this tolerances be listed in the general section of 40 CFR §180.433.

The previously submitted cotton field trial data have now been upgraded to acceptable status 

based on Syngenta’s submission of the requested field trial information. The Agency concludes 

that adequate residue data are available to support the established tolerances of 0.025 ppm each 

for undelinted cottonseed and cotton gin byproducts.

No tolerances are required for meat, milk, poultry, and eggs for the purpose of this petition. 

Syngenta should note that if additional uses are proposed in the future which result in an increase 

in the dietary burden, livestock feeding studies and animal tolerances may be required.

No Codex, Canadian, or Mexican MRLs have been established for residues of fomesafen in/on 

potato or tomato. Canadian MRLs have been established for residues of fomesafen in/on dry

beans, lima beans, snap beans, and soybeans at 0.05 ppm, and a Mexican MRL of 0.05 mg/kg 

has been established for residues of fomesafen in/on soybeans. The registrant has advised the 

Agency that they intend to petition the Canadian government for revised tolerances to address 

any potential harmonization issues raised by establishing the new tolerances requested in this 

action.

A summary of the tolerance reassessment for fomesafen sodium is presented in Table 9. 

Table 9. Tolerance Summary for Fomesafen Sodium

Commodity Established/Proposed

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Proposed Tolerance Under PP#9F7563

Tomato 0.025 0.025

Tolerance Registered Under PP#9F5068

Cotton, gin byproducts 0.025 0.025

Cotton, undelinted seed 0.025 0.025
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

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References

DP#: 325801

Subject: Fomesafen Sodium. Residue Chemistry Summary for the HED Human Health 

Risk Assessment, a Proposal To Amend Use on Soybeans, and Proposals to Add 

Uses on Cotton, Dry Bean, and Snap Bean. PP#1E6228, PP#9F5068, and 

PP#6E4653.

From: D. Davis

To: J. Stone/J. Miller

Dated: 4/25/06

MRIDs: 00158936, 00158937, 40346603, 44754701-44754704, 44754706, 44727901, 

45093601-45093604, 45237101, 45259801, 45268501-45268503, 45313001, &

45342601

CB#: 2253

Subject: PP#4F2997. Amendment of ICI’s Enforcement Analytical Method GAM-RM001/86.

From: W. Chin

To: R. Mountfort and Toxicology Branch

Dated: 8/18/87

MRIDs: 40007101

Attachments: 

Appendix I International Residue Limit Status Sheet

Appendix II Chemical Names and Structures of Metabolites Identified in Tomato Metabolism 

Study (MRID 47473901)

Template Version September 2005
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Appendix I

International Residue Limit Status Sheet

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 5-[2-

chloro-4-

(trifluoromethyl)phenoxy]-

N-(methylsulfonyl)-2-

nitrobenzamide

Common Name:

Fomesafen

X Proposed tolerance

□ Reevaluated tolerance

□ Other

Date: 9/21/09

Codex Status (Maximum Residue Limits) U. S. Tolerances

X No Codex proposal step 6 or above

□ No Codex proposal step 6 or above for the crops 

requested

Petition Number: PP#9F7563

DP#: 365199

Other Identifier: 

Residue definition (step 8/CXL): N/A Reviewer/Branch: M. Metzger/RAB7

Residue definition: fomesafen per se

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

Potato 0.025

Tomato 0.025

Limits for Canada Limits for Mexico

□ No Limits

X No Limits for the crops requested

□ No Limits

X No Limits for the crops requested

Residue definition: 5-[2-chloro-4-

(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-

nitrobenzamide

Residue definition: fomesafen

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

Notes/Special Instructions:

S.Funk, 10/05/2009.
Fomesafen Sodium Summary of Analytical Chemistry and Residue Data DP#s: 365199 and 366116

Page 44 of 44

Appendix II

Chemical Names of Metabolites Identified in Tomato Metabolism Study (MRID 47473901)

Identification of Compounds from Tomato Metabolism Study.

Common name/code

Figure C.3.1 ID No.

Chemical name Chemical structure

Fomesafen 5-[2-chloro-4-(trifluoromethyl)phenoxy]-

N-(methylsulfonyl)-2-nitrobenzamide

F3C

Cl

O

NO2

O

N

H

S

CH3

O

O

R052850 3-chloro-4-hydroxybenzoic acid

HO

Cl

COOH

Cys conjugate of sulfonamide 

(R290493)

2-amino-3-(3 –methanesulfonylaminocarbonyl-4-nitro-phenylsulfany1)-

propionic acid

NO2

O

N

H

S

CH3

O

O

S

H2N

HO O

R012156 2-NO2-5-OH benzoic acid

HO COOH

NO2

R089135 2-NH2-5-OH benzoic acid

HO COOH

NH2