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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

MEMORANDUM

Date: 2/16/11

SUBJECT: Flazasulfuron. Summary of Analytical Chemistry and Residue Data for Use on 

Citrus, Grapes and Sugarcane.

PC Code: 119011 DP Barcodes: D372901, D389318

Decision No.: 425252 Registration No.: 71512-RI

Petition No.: 9F7666 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case No.: NA

TXR No.: NA CAS No.: 104040-78-0

MRID No.: See MRID Summary Table 40 CFR: 180.xxx (pending)

FROM: Nancy Dodd, Chemist

Risk Assessment Branch III (RAB3)

Health Effects Division (HED) (7509P)

THROUGH: Leung Cheng, Senior Chemist

RAB3/HED (7509P)

TO: James Tompkins/Hope Johnson, RM#25

Registration Division (7505P)

Note: This document was originally prepared under contract by Versar, Inc. (6850 Versar Center, Springfield, VA 22151; 

submitted 9/28/10). The document has been reviewed by the Health Effects Division (HED) and revised to reflect current Office 

of Pesticide Programs (OPP) policies.

MRID Summary Table

MRID No. Study Type Comments

47939901 860.1380, 860.1500, 860.1520 New DER; 47939901.der1 (860.1380, 860.1500)

New DER; 47939901.der2 (860.1520)

47939902 860.1380, 860.1500, 860.1520 New DER; 47939902.der1 (860.1380, 860.1500)

New DER; 47939902.der2 (860.1520)

47939903 860.1380 New DER; 47939903.der

47939904 860.1380, 860.1500, 860.1520 New DER; 47939904.der1 (860.1380, 860.1500)

New DER; 47939904.der2 (860.1520)

47939905 860.1300 (plant) New DER; 47939905.der

47939906 860.1300 (plant) New DER; 47939906.der

47939907 860.1300 (plant) New DER; 47939907.der 

47939908 860.1300 (livestock) New DER; 47939908.der 

48092201 860.1340 New DER; 48092201.der
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MRID Summary Table

MRID No. Study Type Comments

48451001 860.1300 (livestock) No DER; additional sample history information

48451002 860.1300 (plant) No DER; additional sample history information

Executive Summary

Flazasulfuron is a sulfonylurea herbicide for control of certain broad-leaf weeds and grasses, and

acts by inhibiting the acetolactate synthase (ALS) biochemical process. Flazasulfuron has been 

registered as a reduced risk product for use on turf grasses in non-residential areas.

ISK Biosciences Corporation, a wholly owned subsidiary of Ishihara Sangyo Kaisha, Ltd., has 

submitted a petition, PP#9F7666, for the establishment of permanent tolerances for residues of 

the herbicide flazasulfuron (N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-

(trifluoromethyl)-2-pyridinesulfonamide) in/on the following raw agricultural commodities 

(RACs):

Citrus........................................................................0.01 ppm

Grapes......................................................................0.01 ppm

Sugarcane.................................................................0.01 ppm

The end-use product relevant for this petition is ISK Flazasulfuron Herbicide, a water dispersible 

granular (WDG/WG) formulation containing 25% active ingredient (ai). The product is 

proposed for use on citrus, grapes, and sugarcane at a maximum single application rate of 0.045 

lb ai/A or a maximum seasonal application rate of 0.15 lb ai/A. The use of a non-ionic surfactant 

is recommended for post-emergence applications to citrus and grapes. The pre-harvest intervals 

(PHIs) for these crops are 1 day for citrus, 75 days for grapes, and 180 days for sugarcane. 

Acceptable metabolism studies on grapes, sugarcane, and tomatoes are available. Residues of 

the parent (flazasulfuron) were not detected in the tomato study and were only detected as a trace 

or minor component in the grape and sugarcane studies. The major metabolites (>10% total 

radioactive residues [TRR]) which were identified were DTPU in grape leaves and grape fruit, 

DTPP in grape leaves, and HTPP (primarily conjugated) and TPSA in tomato fruit. There were 

no major metabolites (>10% TRR) in sugarcane but the primary minor metabolites (<10% TRR) 

were HTPP, TPSA, and ADMP. (Refer to Appendix 2 for chemical names and structures). The 

metabolic pathways for grapes, tomatoes, and sugarcane are similar. The pathways involve

intramolecular rearrangement of the sulfonylurea bridge to form DTPU, followed by hydrolysis 

to form DTPP and HTPP, and cleavage of the sulfonylurea bridge to form TPSA and ADMP.

The grape, sugarcane, and tomato metabolism studies were evaluated by EPA’s Residues of 

Concern Knowledgebase Subcommittee (ROCKS) on 2/15/11. Based on the available 

information, the ROCKS determined that the residue of concern for plants for both the tolerance 

expression and risk assessment is parent. This conclusion is based on the fact that no residues of 

parent or DTPU were found in any field trials.

An acceptable goat metabolism study is available. The major metabolites identified in kidney, 

liver and/or muscle included the parent (flazasulfuron), HTPP, and DTPU. DTPP was identified 
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as a minor metabolite only. The petitioner indicated that flazasulfuron undergoes not only loss 

of the sulfonyl moiety and rearrangement to form DTPU, DTPP, and HTPP, but is further 

metabolized and excreted as HTPU glucuronide, HTPP glucuronide (TPPG), HDTP glucuronide 

(HDTG), and HTPP + O-glucuronide. Chromatographic analysis showed that the radioactivity 

extracted from a tissue type was consistent regardless of label position and yielded little evidence 

of cleavage of the parent molecule by the goat, elimination of the sulfonyl moiety and 

reconnection of the urea bridge notwithstanding.

The goat metabolism study was evaluated by the ROCKS on 2/15/11. Based on the available 

information, the ROCKS determined for the proposed uses that the residue of concern for 

ruminants for both the tolerance expression and risk assessment is parent. There is no concern 

with metabolites because of the low dietary burden associated with the proposed uses.

An adequate residue analytical method using high performance liquid chromatography/tandem 

mass spectrometry with multiple reaction monitoring (HPLC/MS-MS/MRM) (ADME study 

code S09-03106; MRID 48092201) is available for enforcing the proposed tolerances. The 

method underwent a successful independent laboratory validation (ILV) using olives, tomatoes, 

and wheat. The validated limit of quantitation (LOQ) is 0.01 ppm. Radiovalidation is not 

needed since the extraction solvent is the same (acetonitrile:water, 80:20, v/v) in the method 

(MRID 48092201) and in the grape, sugarcane, and tomato metabolism studies (MRIDs 

47939905, 47939906, and 47939907, respectively).

In the field trials and processing studies submitted, residues of flazasulfuron and/or DTPU were 

determined using an adequate HPLC-MS/MS method from Central California Research 

Laboratories, Inc., titled “Analytical Method for Determination of SL-160 and Its Metabolite in 

Soil” (CRL-MTH-045). Residues of parent and DTPU were reported for citrus and grapes, while 

residues of parent were reported for sugarcane. The method was adequately validated both prior 

to and in conjunction with the analysis of the field trial and processing study samples. The 

lowest level of method validation (LLMV) was 0.01 ppm in each matrix tested.

Flazasulfuron and metabolite DTPU are not listed in the FDA PESTDATA database (Pesticide 

Analytical Manual, Volume I, Appendix I, 3rd edition, 1994, revised October 1999). A 

multiresidue method study must be submitted.

Storage stability studies with flazasulfuron demonstrated that the residues are stable for 12 

months in grapes and 183 days in oranges and sugarcane. Residues of the metabolite DTPU are 

also stable for 90 days in grapes and 183 days in oranges. The available storage stability data are 

adequate to support the storage durations and conditions for the RAC samples in this petition. 

Storage stability data were not provided for the processed commodities. As the orange processed 

commodity samples (juice, pulp, and oil) and raisin samples were stored for less than 30 days, no 

supporting storage stability data are required for these commodities. Because the grape juice, 

grape pomace, sugarcane bagasse, molasses, and refined sugar processed commodities were only 

stored for 5 to 12 days longer than the one month threshold, and because the stability of 

flazasulfuron and/or DTPU was demonstrated in the RACs, the available storage stability data 

for flazasulfuron and/or DTPU are adequate to support the storage intervals for the processed 

commodities.
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There are no poultry or swine feedstuffs associated with the subject petition; therefore, data 

requirements pertaining to poultry and swine are not relevant to this petition. 

The ruminant feedstuffs associated with the proposed uses of flazasulfuron are dried citrus pulp 

and sugarcane molasses, each at a maximum of 10% of the diet in beef and dairy cattle. The 

petitioner did not submit a livestock feeding study. Because of the low transfer factors from the 

goat metabolism study and the low predicted residues in cow milk and tissues, HED is waiving 

the requirement for a cow feeding study. If future uses significantly increase the dietary burden, 

livestock feeding studies would be required, in which parent and metabolites HTPP and DTPU 

would be determined.

For all livestock, the proposed uses fall under 40 CFR §180.6(a)(3), i.e., there is no reasonable 

expectation that finite residues will occur in poultry, swine, or ruminant commodities as a result 

of the proposed uses. Therefore, no tolerances are needed for livestock commodities.

Adequate field trial data were submitted supporting the use of the flazasulfuron WDG 

formulation on the proposed crop/crop groups. An adequate number of field trials were

conducted on the required representative crops in the appropriate geographic regions, with the 

exception of citrus in which one lemon trial in Region 3 is missing. An additional lemon field 

trial will not be required because data from the remaining field trials will sufficiently represent 

residues likely to be seen. All trials reflect the proposed use pattern; however, for the sugarcane 

trials, the maximum seasonal application rate was applied in a single application. Residues of 

flazasulfuron and DPTU were separately determined in the citrus and grape field trials; residues 

of flazasulfuron were determined in the sugarcane field trials. Data from these trials are 

sufficient; residues of flazasulfuron and residues of DTPU were all <LOQ (<0.01 ppm). The 

available field trial data will support the proposed tolerance of 0.01 ppm for residues of 

flazasulfuron in/on citrus, grapes, and sugarcane. The tolerance spreadsheet in the Agency’s 

Guidance for Setting Pesticide Tolerances Based on Field Trial Data was not utilized for 

determining appropriate tolerance levels because all of the treated samples bore residues below 

the LOQ.

Processed food/feed studies for citrus (oil, juice, and dried pulp), grape (juice and raisin), and 

sugarcane (molasses and refined sugar) are available. Processing factors for parent could not be 

calculated for any of the processed commodities because no quantifiable residues of parent 

occurred. Therefore, separate tolerances are not required for the processed commodities of citrus 

(oil, juice, and dried pulp), grape (juice and raisin), and sugarcane (molasses and refined sugar).
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There are no rotational crop data requirements associated with the use on citrus or grapes

(OPPTS 860.1850). The rotational crop guidelines are applicable for sugarcane; however, 

rotational crop data have not been submitted. The proposed label for sugarcane requires a 12-

month interval between the last application and the planting of the rotational crop. While HED 

considers this restriction to be adequate for conditional registration of flazasulfuron based on the 

fact that no detectable residues of flazasulfuron were found in the primary crops, the restriction 

will need to be re-evaluated after submission and review of the confined rotational crop study

which is required to support permanent registration of sugarcane.

No Codex, Canadian, or Mexican maximum residue limits (MRLs)/tolerances have been 

established for residues of flazasulfuron.

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for flazasulfuron. Pending submission of a 

revised Section B (see requirements under Directions for Use) and a revised Section F (see 

requirement under Proposed Tolerances), there are no residue chemistry issues that would 

preclude granting permanent tolerances on citrus, grape, and sugarcane and conditional 

registration for ISK Flazasulfuron Herbicide (EPA Reg. No. 71512-RI) on citrus, grape, and 

sugarcane. Tolerances for residues of flazasulfuron are recommended as follow:

Fruit, citrus, group 10-10 .........................................0.01 ppm

Grape........................................................................0.01 ppm

Sugarcane.................................................................0.01 ppm

As conditions of registration, the remaining deficiencies listed below must be resolved.

A human health risk assessment is forthcoming.

Note to PM: 

The tolerance expression for flazasulfuronl in 40 CFR §180.xxx should be stated according 

to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner) as follows: 

“Tolerances are established for residues of flazasulfuron, 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 flazasulfuron (N-[[(4,6-

dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(trifluoromethyl)-2-pyridinesulfonamide).”
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• The Section B/label should be changed to clarify/revise the minimum retreatment interval

(RTI). The general label application restrictions state that repeat applications may be 

made at 2 to 6 weeks after application. However, the label also states that split 

applications should be made at 4 to 6 weeks after the first application, and that sequential 

applications are made on a longer term interval such as spring followed by a fall 

application. The petitioner should also consider that the label directions regarding the 

RTI should reflect the field trials. The retreatment intervals for citrus in the field trials 

were 95-308 days for citrus and 14-118 days for grapes. Based on the residue data, the 

retreatment interval should be at least 3 months for citrus and at least 2 weeks for grapes.

860.1200 Directions for Use

• The proposed label for sugarcane requires a 12-month interval between the last 

application and the planting of the rotational crop. While HED considers this restriction 

to be adequate for conditional registration of flazasulfuron based on the fact that no 

detectable residues of flazasulfuron were found in the primary crops, the restriction will 

need to be re-evaluated after submission and review of the confined rotational crop study 

which is required to support permanent registration of sugarcane.

• The petitioner is required to submit multiresidue methods data since tolerances will be 

established. 

860.1360 Multiresidue Methods

860.1380 Storage Stability Data

• For MRID 47939903 (Howald, M., Ullrich-Mitzel, A. (1997) Storage Stability of SL-160 

Residues in Grapes. Document Number: 634713), the petitioner must provide dates of 

sample spiking and analysis to verify reported storage intervals.

860.1550 Proposed Tolerances

• The petitioner must submit a revised Section F to propose tolerances which reflect the 

correct commodity definitions as specified in Table 11.

• A confined rotational crop study is required to support permanent registration of 

sugarcane. Depending on the results, a study to determine field accumulation in 

rotational crops may be required.

860.1850/860.1900 Confined/Field Accumulation in Rotational Crops

Background

Flazasulfuron is a herbicide developed by ISK Biosciences Corporation for control of certain 

broadleaf weeds and grasses in citrus, grapes, and sugarcane. Flazasulfuron has also been 

proposed for use on Christmas trees and industrial vegetation management in nonagricultural 

areas. This is the first food/feed use for flazasulfuron. Flazasulfuron is registered for use on turf.

Flazasulfuron acts by inhibiting the acetolactate synthase (ALS) biochemical process.

 
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The chemical name and structure of flazasulfuron are listed below in Table 1. The 

physicochemical properties of flazasulfuron are listed in Table 2.

Table 1. Flazasulfuron Nomenclature.

Compound Chemical Structure

Common name Flazasulfuron

Company experimental name SL-160

IUPAC name 1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-trifluoromethyl-2-pyridylsulfonyl)urea

CAS name N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(trifluoromethyl)-2-

pyridinesulfonamide

CAS registry number 104040-78-0

End-use product (EP) ISK Flazasulfuron Herbicide, a WDG/WG formulation containing 25% active ingredient (ai)

(EPA File Symbol 71512-RI), for use on citrus, grapes, and sugarcane; Flazasulfuron 25WG 

(EPA Reg. No 71512-12), registered on turf

Table 2. Physicochemical Properties of Flazasulfuron.

Parameter Value Reference

Melting point 150°C MRID 46220905

pH 4.01 at 25°C (1% w/w)

Density 0.66 g/cm3 at 25°C (bulk density)

Water solubility (25°C) pH 5 buffer 0.027 mg/mL

pH 7 buffer 2.1 mg/mL

pH 9 buffer not stable

Solvent solubility (25°C) Acetone 22.7 mg/mL

Acetonitrile 8.7 mg/mL

Dichloromethane 22.1 mg/mL

Ethyl acetate 6.9 mg/mL

Hexanes* 0.50 μg/mL

Methanol 4.2 mg/mL

Octanol 0.20 mg/mL

Toluene 0.56 mg/mL

Vapor pressure <1 x 10-7 torr (<1.33 x 10-5 Pa) at 25, 35, 

and 45°C

Dissociation constant (pKa) at 20°C 4.37 

Octanol/water partition coefficient 

Log(KOW) at 25°C

Kow = 20.0 in pH 5 buffer

Kow = <10 in pH 7 buffer

UV/visible absorption spectrum Not reported

*n-hexane with various methylpentanes
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860.1200 Directions for Use

ISK Bioscience Corporation has submitted a copy of the proposed use directions for the 25% ai 

WDG formulation of flazasulfuron (ISK Flazasulfuron Herbicide; EPA File Symbol 71512-RI) 

on citrus, grapes, and sugarcane. The proposed use directions are presented in Table 3 below. 

Table 3. Summary of Directions for Use of Flazasulfuron.

Applic. Timing, 

Type, and Equip.

Application

Rate 

(lb ai/A)

Max. No. 

Applications

per Season

Max. 

Seasonal 

Application

Rate

(lb ai/A)

Minimum 

RTI 

(days)

PHI

(days) Use Directions and Limitations

Citrus

Pre-emergence and 

Post-emergence; 

Soil application 

using ground spray 

equipment

0.045 Not reported 0.15 Not 

reported1 1

Apply only as a directed spray to the soil 

beneath the trees. 

Use a non-ionic surfactant at 0.25% v/v for 

post-emergence applications.

Grapes

Pre-emergence and 

Post-emergence; 

Soil application 

using ground spray 

equipment

0.045 Not reported 0.15 Not 

reported1 75

Apply only as a directed spray to the soil 

beneath the vines.

Use a non-ionic surfactant at 0.25% v/v.

Sugarcane

Over-the-Top or 

Post-directed 0.023 Not reported 0.15 14 180

Apply prior to spiking or on ratoon up to 

24 inches tall at a 0.014 lb ai/A rate.

Use a non-ionic surfactant at 0.25% v/v.

Allow a 12 month interval between the last 

application and the planting of the 

rotational crop.

Post-Directed 0.045 Not reported 0.15 14 180

Apply to sugarcane that is 18 inches tall up 

through layby. Applications should 

minimize contact with the whorl of the 

sugarcane.

Use a non-ionic surfactant at 0.25% v/v.

Allow a 12 month interval between the last 

application and the planting of the 

rotational crop. 1 A retreatment interval specifically for citrus and grapes was not provided. A generic retreatment interval was provided.

General application information on the label states that pre-emergence and post-emergence 

applications should be made in 15 to 50 gallons of water per acre. For directed post-emergence 

sprays, a spray volume of 20 gallons or more per acre is recommended. Applications should be 

made using conventional low pressure ground spray equipment. Applications cannot be made 

aerially or through any irrigation system. The general label application restrictions also state that 

repeat applications may be made at 2 to 6 weeks after application. However, the label also states 

that split applications should be made at 4 to 6 weeks after the first application, and that 
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sequential applications are made on a longer term interval such as spring followed by a fall 

application. 

HED Conclusions. The Section B/label should be changed to clarify/revise the minimum 

retreatment interval. The general label application restrictions state that repeat applications may 

be made at 2 to 6 weeks after application. However, the label also states that split applications 

should be made at 4 to 6 weeks after the first application, and that sequential applications are 

made on a longer term interval such as spring followed by a fall application. The petitioner 

should also consider that the label directions regarding the retreatment interval should reflect the 

field trials. The retreatment intervals for citrus in the field trials were 95-308 days for citrus and 

14-118 days for grapes. Based on the residue data, the retreatment interval should be at least 3 

months for citrus and at least 2 weeks for grapes. 

The proposed label for sugarcane requires a 12-month interval between the last application and 

the planting of the rotational crop. While HED considers this restriction to be adequate for 

conditional registration of flazasulfuron based on the fact that no detectable residues were found 

in the primary crops, the restriction will need to be re-evaluated after submission and review of 

the confined rotational crop study which is required to support permanent registration.

860.1300 Nature of the Residue – Plants

DER References: 47939905.der (grapes), 47939906.der (sugarcane), 47939907.der (tomatoes)

Grapes

47939905.der

ISK Biosciences Corporation has submitted a study investigating the metabolism of [pyridyl- 14C]flazasulfuron (P-label; specific activity 113-137 μCi/mg) and [pyrimidinyl14C]flazasulfuron 

(Pm-label; 122 μCi/mg) in grape vines grown in treated soil under field and greenhouse 

conditions. As shown in Table 4 below, the test substances were radiolabeled at the 2- or 5-

positions, respectively, of the pyridyl or pyrimidinyl rings. 

TABLE 4. Test Material Characteristics.

Field Study

Chemical structure

Radiolabel position [

14C-pyridyl]-flazasulfuron

(P label)

[

14C-pyrimidinyl]-flazasulfuron

(Pm label)

The test substances, diluted with water, were applied as a spray application to the soil around 

grape vines grown either outdoors or in a greenhouse at a target rate of 0.045 lb ai/A per 

application (50 g ai/ha/application). In both the field and greenhouse, there were two sets of 

plants: one set received a single application and the second set received two applications. For 
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plants receiving two applications, the first application was made at early bud break or at post bud 

break when vines were approximately 10 feet in height and the second application was made 

seven or eight weeks after the first. For plants receiving two applications, the total seasonal 

application rate was 0.089 lb ai/A (100 g ai/ha). Samples of foliage and grapes were collected at 

maturity (85 days after the second application for the field study and 34 days after the second 

application for the greenhouse study). The in-life phase of the field study was conducted by 

Plant Sciences, Inc. (PSI; Watsonville, CA), and the in-life phase of the greenhouse study and 

the analytical phase of both studies were conducted by Ricerca, LLC (Painesville, OH). 

Total radioactive residues (TRR) for the 0.089 lb ai/A treatment plots (i.e. two applications), as 

determined by combustion/liquid scintillation counting (LSC) of sample extracts, were <10 ppb 

in grape fruit from both the field and greenhouse studies for the Pm-label. For the P-label, TRR 

in grape fruit was <10 ppb in the greenhouse study as well. No grape fruits were obtained from 

the P-label field study. In the grape leaves, TRR was 164.2 ppb for the P-label and 51.5 ppb for 

the Pm-label from the field study and 18.9 ppb for the P-label and 47.1 ppb for the Pm-label 

from the greenhouse study. The samples from the 0.089 lb ai/A treatment plots were analyzed 

for 14C-residue distribution. 

Total radioactive residues (TRR) for the 0.045 lb ai/A treatment plots (i.e. one application), as 

determined by combustion/LSC of sample extracts, were <10 ppb in the grape fruit from the 

greenhouse study for both the P-label and Pm-label. For the field study, TRR in grape fruit was 

not detected for the Pm-label. No grape fruits were obtained from the P-label field study. TRR 

in grape leaves was not reported for either the field or greenhouse single-application studies. 

The samples from the single-application studies were not analyzed for 14C-residue distribution.

No storage stability data are required to support the study because all samples were stored frozen 

and were analyzed within 4.5 months of collection.

The majority of the radioactivity for both labels was released from grape leaves with acetonitrile 

(ACN)/water solvent extraction (~91-92% TRR for field study and ~76-83% TRR for 

greenhouse study). The extracted residues were partitioned into organic (30.4-67.9% TRR for 

the field study and 52.9-56.1% TRR for the greenhouse study) and aqueous (22.7-62.0% TRR 

for the field study and 23.1-27.2% TRR for the greenhouse study) fractions. Nonextractable 

residues were 4.8-12.4 ppb (7.6-9.3% TRR) in field-grown grape leaves and 3.2-11.3 ppb (16.7-

24.1% TRR) in greenhouse-grown grape leaves. These procedures adequately extracted the 

majority of residues from grape leaves. Extraction and partitioning results were normalized by 

the petitioner, resulting in accountabilities of 100%.

In field-grown grape plants, the majority of the radioactivity for the Pm-label was released from 

grape fruit with ACN/water solvent extraction (~91% TRR). The extracted residues were 

partitioned into organic (61.9% TRR) and aqueous (28.6% TRR) fractions. Nonextractable 

residues were 0.2 ppb (9.5% TRR) in grape fruit. In greenhouse-grown grape plants, the 

majority of the radioactivity for both labels was released from grape fruit with ACN/water 

solvent extraction (~88-91% TRR). The extracted residues were partitioned into organic (47.1-

57.5% TRR) and aqueous (33.4-40.6% TRR) fractions. Nonextractable residues were 0.1-0.3 

ppb in grape fruit (9.1-12.3% TRR). Extraction and partitioning results were normalized by the 
Page 11 of 33

petitioner, resulting in accountabilities of 100%.

The metabolic profiles were similar for both labels in both the field and greenhouse studies. In 

grape leaves, trace amounts of parent flazasulfuron were detected in the organic fraction for both 

labels, accounting for 0.22-2.04% TRR, 0.3-0.5 ppb. The major metabolites found in the organic 

fraction of leaf extracts for both labels were DTPU (5.78-50.90% TRR, 5.4-26.2 ppb) and DTPP 

(1.16-10.21% TRR, 0.8-5.3 ppb). Trace amounts of HTPP (0.7-1.72% TRR, 0.3-1.1 ppb) were 

also identified. In P-label grape leaves, Metabolite ‘H’ was tentatively identified in the organic 

fraction at 12.75-18.76% TRR (2.4-30.8 ppb) along with trace amounts of TPSA at 1.74-2.36% 

TRR (0.4-2.9 ppm). In the aqueous fractions of the P-label grape leaves, Metabolite ‘S’ was 

tentatively identified at 14.70-16.01% TRR, 3.0-24.1 ppb. A 14C peak with a retention time of 

16.7 minutes was isolated from the aqueous extract (P-label) and did not match any provided 

standard. The conjugate was further characterized by sequential acid hydrolysis (1 N HCl for

~18 hours at 40 °C) and base hydrolysis (1 N NaOH for ~18 hours at 40 °C). The results show 

that the isolated sample coeluted with the standard TPSA, accounting for 6.11-35.23% TRR, 1.2-

57.8 ppb. Two unknowns in Pm-label grape leaf samples, neither present at >8.0 ppb, accounted 

for 17.06 -18.84% TRR.

A few potential discrepancies are noted: 1) For the P-label greenhouse grown grape leaves and 

grape fruit, it appears that the petitioner may have reversed the %TRR for the TPSA Conjugate 

and Metabolite ‘S’; 2) Metabolite H was reported in the organic phase of the P-label greenhouse 

grown grapes, but this compound was not shown on the HPLC chromatogram; and 3) for the Plabel greenhouse grown grape fruit, the %TRR for the identified metabolites may be incorrect as 

it appears that the petitioner calculated the metabolite %TRRs using the incorrect aqueous phase 

and organic phase %TRR (i.e. the petitioner reversed the aqueous and organic phase %TRRs). 

The major metabolic pathway of flazasulfuron in grapes involves the rearrangement of 

sulfonylurea bridge to form DTPU and cleavage between the pyridyl and pyrimidine ring to give 

TPSA and TPSA related residues.

Sugarcane

47939906.der

ISK Biosciences Corporation has submitted a study investigating the metabolism of [pyridyl- 14C]flazasulfuron (P-label; specific activity 137 μCi/mg) and [pyrimidinyl14C]flazasulfuron 

(Pm-label; 122 μCi/mg) in sugarcane grown in treated soil under greenhouse conditions. As 

shown in Table 4 above, the test substances were radiolabeled at the 2- or 5-positions, 

respectively, of the pyridyl or pyrimidinyl rings. The radiolabeled test substances were 

formulated as water dispersible granular (WDG) formulations and applied as two soil 

applications to potted sugarcane at the two to three leaf stage and again at the five to six leaf 

stage (re-treatment interval of 23 to 25 days). Both 1x and 3x treatment plots were established, 

with the 1x treatment plot receiving two applications at 0.067 lb ai/A (75 g ai/ha) for a total of 

0.134 lb ai/A (150 g ai/ha) and the 3x treatment plot receiving two applications at 0.20 lb ai/A 

(225 g ai/ha) for a total of 0.40 lb ai/A (450 g ai/ha). Sugarcane samples were collected 

following the second application at nominal intervals of 0 days, 30 days, 100 days, and at final 

maturity (364 to 367 days). The in-life phase of the study was conducted by Plant Sciences, Inc. 
Page 12 of 33

(PSI; Watsonville, CA). 

Total radioactive residues (TRRs) were determined by liquid scintillation counting (LSC) of the 

entire plant samples (entire above ground portion) for Days 0 and 30 and of stalk only for Day 

100 and at final maturity. For the 0.134 lb ai/A plots, TRR declined from 1.074 to 0.0059 ppm 

for the P-label treatment and from 1.299 to 0.0053 ppm for the Pm-label treatment. For the 0.40 

lb ai/A plots, TRR declined from 2.684 to 0.010 ppm for the P-label treatment and from 5.509 to 

0.0076 ppm for the Pm-label treatment. Only samples collected at maturity from the 0.40 lb ai/A 

treatment plot were analyzed for 14C-residue distribution.

Initial sample analysis was completed in less than 4.3 months. Samples were re-extracted and 

analyzed up to 8 months after the initial analysis. The results after 8 months were similar to the 

initial results and were averaged together by the petitioner. 

Radioactivity released from the sugarcane stalks with ACN/water solvent extraction was 59.9% 

for the P-label and 39.5% for the Pm-label. The extracted residues were partitioned into organic 

and aqueous fractions using a low polarity solvent (DCM at pH 5). Residues mainly remained in 

aqueous phases, accounting for 42.5% TRR in the P-label and 25.4% TRR in the Pm-label. The 

organic phase accounted for 8.5% TRR (Pm-label) to 12.5% TRR (P-label). Nonextractable 

residues were 4.0 ppb (40.1% TRR) for the P-label and 4.6 ppb (60.5% TRR) for the Pm-label. 

Bound residues could not be further characterized due to the low TRR levels. Approximately 

5% TRR was lost during the partition due to the formation of unrecovered insolubles.

In sugarcane stalks, parent flazasulfuron accounted only for a minor portion of the residue, at 

1.02% TRR or 0.08 ppb (Pm-label) to 1.53% TRR or 0.153 ppb (P-label). The major 

metabolites identified were HTPP, TPSA (P-label metabolite only) and ADMP (Pm-label 

metabolite only). HTPP accounted for 2.6% TRR (0.26 ppb; P-label) to 3.8%TRR (0.29 ppb; 

Pm-label); TPSA accounted for 5.91% TRR (0.591 ppb; P-label); and ADMP accounted for 

6.68% TRR (0.51 ppb; Pm-label). It was noted, however, that TPSA might be an unknown that 

retained both ring systems, based on the fact that peaks at very close retention times to TPSA 

were observed in both the organic and aqueous phases of the Pm-label. DTPU was found in the 

organic fraction from both labels, though only at a very small level in the P-label (0.72% TRR, 

0.072 ppb) and at <LOQ in the Pm-label. DTPP was also found in the organic fraction from 

both labels, but was <LOQ. Organosoluble unknowns included four peaks in the P-label, each 

less than 1.92% TRR (0.192 ppb) and four peaks in the Pm-label, each less than 2.86%TRR 

(0.22 ppb). Four of the P-label and Pm-label organosoluble unknowns had similar retention 

times. Aqueous unknowns included three peaks in the P-label, with each representing 2.6% to 

16.8% TRR (0.261 to 1.68 ppb) and four peaks in the Pm-label, with each representing 0.26% to 

12.2% TRR (<0.038 to 0.929 ppb). Only one P-label and Pm-label aqueous unknowns had a 

similar retention time. It was the most polar component.

The major metabolic pathway of flazasulfuron in sugarcane involves 1) the intramolecular 

rearrangement of parent flazasulfuron to form DTPU, and hydrolysis to DTPP and HTPP; and 2) 

cleavage at the sulfonylurea bridge to form TPSA and ADMP. 
Page 13 of 33

Tomatoes

47939907.der

ISK Biosciences Corporation has submitted a study investigating the metabolism of [14CP]flazasulfuron (P-label; specific activity 113 μCi/mg) and [14C-Pm]flazasulfuron (Pm-label; 122 

μCi/mg) in tomato plants grown in 10 inch pots under field conditions. As shown in Table 4 

above, the test substances were radiolabeled at the 2- or 5-positions, respectively, of the pyridyl 

or pyrimidinyl rings. The test substances were formulated as a suspension and applied once as a 

foliar spray at a target rate of 0.045 lb ai/A/application (50 g ai/ha/application) and at an 

exaggerated application rate of 0.178 lb ai/A/application (200 g ai/h/application). There were 

four treatment groups of four plants each and one control group of four plants. The first two 

treatment groups received either [14C-P]flazasulfuron or [14C-Pm]flazasulfuron as a single 

application at the normal target rate and the second and third treatment groups received either 

[

14C-P]flazasulfuron or [14C-Pm]flazasulfuron as a single application at the exaggerated 

application rate. The applications were made 14 days after the tomato plants were transplanted 

into the 10 inch pots and moved outdoors. Fourteen days after the application, a plant from each 

treatment group was harvested. There was no fruit present at this time so only a portion of the 

leaves and vines were collected. Upon maturity (83 days after application), tomato fruits, stems 

and leaves were collected. The in-life phase of the field study and the analytical phase of both 

studies were conducted by Ricerca, LLC (Painesville, OH).

A sample history table was provided which contains the dates of collection, processing, 

radioassay, extraction, and analysis (MRID 48451002). Leaf/vine samples harvested on 7/11/96 

(intermediate harvest) were extracted and analyzed on 8/8/96. The final harvest of red fruit, 

green fruit, and leaf/vine occurred on 9/16/96. The HPLC analyses of juice, pomace, and 

leaf/vine were conducted between 9/25/96 and 10/10/96. Samples were stored under freezer 

conditions, typically defined as ≤-15°C. The data indicate that the tomato metabolism samples 

were analyzed within 6 months of collection; therefore, the metabolic profile of the samples is

considered to be stable for the duration of the study.

The total radioactive residues (TRRs) in mature tomato fruits were determined as a sum of 

contributions from juice and pomace fractions. The TRR was less than 10 ppb in all samples. 

For the 0.045 lb ai/A treatment plots, TRR in whole tomatoes was 1.55 ppb for the P-label and 

1.35 ppb for the Pm-label. For the 0.178 lb ai/A treatment plot, TRR in whole tomatoes was 

7.96 ppb for the P-label and 3.17 ppb for the Pm-label. 

Only juice and pomace from the 0.045 lb ai/A treatment plots were analyzed for 14C-residue 

distribution. Tomato samples (including fruit, leaf, and stem) from the exaggerated rate 

treatment were used for metabolite isolation and identification. 

The TRR presented for 14C-residue distribution in the juice and pomace fractions is in terms of 

whole fruit. The majority of the radioactivity for both labels was concentrated in the juice (75% 

and 77% TRR, respectively). The remaining radioactivity was found in the pomace (25% and 

23% TRR, respectively). The pomace was extracted with ACN/water solvent. For the P-label

pomace, the majority of the radioactivity was extracted (18.8% TRR, 0.3 ppb), with 6.3% (0.1 

ppb) left in the post-extracted solid. For the Pm-label pomace, the majority of the radioactivity 
Page 14 of 33

was left in the post-extracted solid (15.4% TRR, 0.2 ppb), with only 7.7% TRR (0.1 ppb) in the 

extract. Overall, approximately 85% to 94% TRR was solubilized as juice and pomace extracts. 

Due to the low levels of 14C residues present as unextractable, no further characterization was 

necessary of the post-extracted solid.

The metabolic profiles were similar for both labels. Residues of the parent flazasulfuron were 

not detected in any of the samples. HTPP was identified as the major metabolite, the majority of 

which was present as a conjugate in all of the juice and pomace samples. For the whole tomato 

(sum of juice and pomace), the HTPP conjugate residue was 18.7% to 33% TRR (0.2 to 0.5 ppb) 

and the HTPP metabolite was 2.0% to 4.3% TRR (<0.05 ppb). Minor metabolites included 

DTPU (7.8% TRR; both labels), TPSA (13.6% TRR; P-label only) and ADMP (3.3% TRR; Pmlabel only). Also characterized were polar metabolites (6.9% TRR in P-label and 37.7% TRR in 

Pm-label), three unknown metabolites (4.1% TRR to 12.1% TRR) and a small number of minor 

peaks.

The major metabolic pathway of flazasulfuron in tomato fruit and vines involves the 

rearrangement of the sulfonylurea bridge to form DTPU, followed by hydrolysis to form HTPP, 

and cleavage of the sulfonylurea linkage to form TPSA and ADMP. Primary metabolites are 

further metabolized to more polar products involving conjugation reactions.

HED Conclusions. The nature of the residue studies on grapes, sugarcane, and tomatoes are 

adequate. The grape, sugarcane, and tomato metabolism studies were evaluated by EPA’s 

Residues of Concern Knowledgebase Subcommittee (ROCKS) on 2/15/11. Based on the 

available information, the ROCKS determined that the residue of concern for plants for both the 

tolerance expression and risk assessment is parent. This conclusion is based on the fact that no 

residues of parent or DTPU were found in any field trials.

860.1300 Nature of the Residue - Livestock

DER Reference: 47939908.der

Ruminants

47939908.der

Ishihara Sangyo Kaisha, Ltd. has submitted a study investigating the metabolism of [pyridyl- 14C]flazasulfuron (P-label) and [pyrimidinyl14C]flazasulfuron (Pm-label) in the lactating goat; 

the specific activity was 4.81 and 4.89 MBq/mg for each radiolabel, respectively. As shown in 

Table 4 above, the test substances were radiolabeled at the 2- or 5-positions, respectively, of the 

pyridyl or pyrimidinyl rings. The test substances were administered orally via capsule to two 

goats (one goat per radiolabel) at average dosing rates of 11.4 ppm (P-label) and 14.3 ppm (Pmlabel) in the diet for 3 consecutive days. A third goat was treated with capsules containing 

carrier only, as a control. Milk was collected twice daily throughout the study, in the morning 

after dose administration and in the afternoon; urine and feces were collected twice daily; and 

tissues, including muscle (composite of loin and hindquarter), fat (composite of renal and 

omental), liver, and kidneys, were collected at sacrifice, 23-24 hours after the final dose. The inlife phase and the analytical phase of the study were conducted by WIL Research Laboratories,
Page 15 of 33

LLC (Ashland, OH).

A sample history table was provided which contains the sample history, including dates of 

collection, tissue processing, radioassay, extraction, and analysis (MRID 48451001). Storage 

temperatures were also provided. Samples were collected on February 6, 2009 and stored at

-20°C. After tissue processing, samples were stored at -20°C; extracts were stored at 2-8°C. 

HPLC analyses of liver, kidney, muscle and milk were conducted on March 17-18, 2009. 

Additional samples of liver and kidney were extracted on July 15, 2009 and analyzed by HPLC 

on July 24, 2009; the results indicated that the radioactive residue profile did not significantly 

change over the course of the study. The data indicate that the goat metabolism samples were 

analyzed within 6 months of collection; therefore, the metabolic profile of the samples is

considered to be stable for the duration of the study.

Total radioactive residues (TRRs) in samples were determined by combustion and liquid 

scintillation counting (LSC) or by direct LSC. TRR in milk was typically higher in the afternoon 

samples. Maximum levels were observed in afternoon samples on Day 3 (0.022 ppm) in P-label 

milk and Days 2 and 3 (0.010 ppm) in Pm-label milk. TRR was <0.01 ppm in fat (both labels) 

and Pm-label milk and muscle; residues in these samples were not further investigated. In Day 4 

morning milk and remaining tissues, TRRs were ≥0.01 ppm: 0.021, 0.049, 0.166, and 0.352 ppm 

in P-label milk, muscle, kidney, and liver, respectively, and 0.026 and 0.055 ppm in Pm-label 

kidney and liver. Only P-label liver and kidney contained radioactive residues >0.1 ppm. The 

majority of the applied dose (90-91%) was excreted: 82-86% in urine and 5-9% in feces.

The majority of the radioactivity was solvent extracted with acetone (milk) and ACN (tissues) 

from P-label milk (~91% TRR), kidney (both labels; ~85-87% TRR), and muscle (both labels; 

~88-90% TRR). Solvent extraction released lower amounts of radioactivity from Pm-label milk 

(~57% TRR) and liver (both labels; ~45-64% TRR). In P-Label milk after partition with hexane,

the majority of the radioactivity (~70% TRR) remained in the aqueous phase. Fractionation of 

the aqueous phase by C18 solid phase extraction (SPE) resulted in ~46% TRR and lesser 

amounts in subsequent increasingly non-polar fractions. Unextractable residues remaining after 

the initial extraction of samples of liver and kidney (both labels) and muscle (P-label) were 

further extracted with ACN/MeOH which released an additional 5% TRR from liver, 5-9% from 

kidney, and 7% from muscle. Unextractable residues remaining after the second extraction of 

samples of liver and kidney (both labels) and muscle (P-label) were sequentially subjected to 

mild acid and base hydrolysis which released ~30-31% TRR from liver, ~3-6% from kidney, and 

~2% from muscle. Unextractable residues in liver samples (both labels) were sequentially 

subjected to strong acid and base hydrolysis which released an additional ~2-8% TRR. 

Unextractable residues remaining after extraction/hydrolysis were not reported.

Residues were initially identified and quantitated by HPLC. Identification of flazasulfuron and 

its metabolites was confirmed in P-label liver, kidney, and muscle by thin layer cochromatography. Samples were stored frozen prior to analysis, but no information pertaining to 

storage intervals was provided. To support storage durations, samples of liver (both labels) and 

kidney (both labels) were re-extracted and analyzed by HPLC following frozen storage;

however, no dates were provided. 

In goat milk, the low level of radioactivity in the extract was characterized as polar based on its 
Page 16 of 33

hexane partition behavior. The parent, flazasulfuron, was the major residue identified in Pmlabel kidney, accounting for 59.7% TRR (0.016 ppm) and a minor residue in P-label kidney at 

16.6% TRR (0.028 ppm). The parent was not identified in liver and muscle. The metabolite M7 

(HTPP) was the major residue identified in P-label liver at 40.2% TRR (0.142 ppm), P-label 

muscle at 89.6% TRR (0.044 ppm), and Pm-label liver at 31.5% TRR (0.017 ppm). M7 (HTPP) 

was also identified as a minor residue in P-label kidney at 13.4% TRR (0.022 ppm) and not 

identified in Pm-label kidney. Metabolite M8 (DTPU) was the major residue in P-label kidney at 

50.2% TRR (0.083 ppm) and a minor residue in Pm-label kidney at 17.6% TRR (0.005 ppm). 

Metabolite M9 (DTPP) was a minor residue in kidney (both labels) accounting for 4.5-9.1% 

TRR (0.002-0.007 ppm). Discrete unknowns in P-label liver samples accounted for up to 23.3% 

TRR, with none present at >0.026 ppm. Discrete unknowns in Pm-label liver samples accounted 

for up to 13.6% TRR, with none present at >0.004 ppm.

Based on the goat metabolism study, the petitioner indicated that flazasulfuron undergoes not 

only loss of the sulfonyl moiety and rearrangement to form DTPU, DTPP, and HTPP, but is 

further metabolized and excreted as HTPU glucuronide, HTPP glucuronide (TPPG), HDTP 

glucuronide (HDTG), and HTPP + O-glucoronide. Chromatographic analysis showed that the 

radioactivity extracted from a tissue type was consistent regardless of label position and yielded 

little evidence of cleavage of the parent molecule by the goat, elimination of the sulfonyl moiety 

and reconnection of the urea bridge notwithstanding.

Poultry

No poultry metabolism study was submitted but none is required since no poultry feed items are 

associated with citrus, grapes, and sugarcane.

HED Conclusions. The metabolism study using goats is adequate.

The goat metabolism study was evaluated by the ROCKS on 2/15/11. Based on the available 

information, the ROCKS determined for the proposed uses that the residue of concern for 

ruminants for both the tolerance expression and risk assessment is parent. There is no concern 

with metabolites because of the low dietary burden associated with the proposed uses. 

Since no poultry feed items are associated with citrus, grapes, and sugarcane, a poultry 

metabolism study is not needed.
Page 17 of 33

860.1340 Residue Analytical Methods

DER References: 48092201.der (grape ILV), 47939901.der1 (citrus), 47939901.der2 (citrus), 47939902.der1 (grape), 

47939902.der2 (grape), 47939904.der1 (sugarcane), 47939904.der2 (sugarcane)

Plant

Enforcement

48092201.der

An adequate residue analytical method (ADME study code S09-03106; MRID 48092201) which 

uses high performance liquid chromatography/tandem mass spectrometry with multiple reaction 

monitoring (HPLC/MS-MS/MRM) to quantitate residues of flazasulfuron in various crops is 

available for enforcing the proposed tolerances. The monitored ion transitions are 408→182 for 

quantitation and 408→83 for confirmation.

A successful ILV of the method described in the final report of ADME study code S09-03106

was performed. ISK Bioscience Corporation has submitted the results from the independent 

laboratory validation (ILV), which was conducted by Eurofins Dr. Specht GLP GmbH in 

Hamburg, Germany. The laboratory reported that the method presented in ADME study code 

S09-03106 was followed as written with a few minor exceptions. These exceptions were: (1) use 

of the mass transition 408→83 for confirmation purposes instead of the mass transition 

408→227, and (2) use of a slightly different column with adapted HPLC conditions. These 

changes were not significant and had no impact on the study. Acceptable recoveries were 

obtained from olives (fruit), tomatoes (fruit), and wheat (grain) fortified with flazasulfuron at the 

method LOQ (0.01 ppm) and 10x the LOQ (0.10 ppm). 

Homogenized olives, tomatoes, and wheat samples were fortified at the limit of quantitation 

(0.01 ppm) and 10x the LOQ (0.10 ppm). Residues of flazasulfuron were extracted from crop 

samples each weighing 20 grams with a mixture of acetonitrile/water (80/20, v/v), filtrated over 

paper filters and then further purified over an Oasis HLB cartridge and through a solid-phase 

extraction (SPE) cartridge. An extra liquid-liquid partition step was added in between for the 

olive high fat content matrix only. Dry matrices (wheat) were immersed into water overnight 

before the extraction step.

Data-Collection

In the current field trial and processing studies submitted by Ishihara Sangyo Kaisha, Ltd., the 

residue data were collected using an HPLC-MS/MS method (CCRL-MTH-045) from Central 

California Research Laboratories, Inc., titled “Analytical Method for Determination of SL-160 

and Its Metabolite in Soil.” Residues of parent and DPTU were reported for citrus and grapes, 

while residues of parent were reported for sugarcane. Ions monitored were 408.1→181.7 for 

parent and 344.0→301.0 for DTPU.

Briefly, samples of homogenized orange RAC, orange pulp, grape RAC, raisin, grape pomace, 

sugarcane RAC, and bagasse were extracted with acetonitrile:water (80:20, v:v), centrifuged, 

filtered, and diluted with 15% acetonitrile:85% HPLC grade water prior to analysis by HPLCMS/MS. Orange juice and grape juice samples were extracted with acetonitrile:water (80:20, 
Page 18 of 33

v:v), hand-shaken, centrifuged, and then handled the same as the orange and grape RAC 

samples. Orange oil samples were vortexed for 30 seconds with methanol, filtered, diluted, and 

analyzed following the procedure for the orange RAC samples. For molasses and refined sugar 

samples, aliquots were extracted with water. The mixture was shaken by hand for 5-10 seconds 

and otherwise handled the same as the sugarcane RAC samples.

Method CCRL-MTH-045 was adequately validated both prior to and in conjunction with the 

analysis of the field trial and processing study samples. For method validation and concurrent 

recovery analysis, control samples were fortified with flazasulfuron and/or DPTU separately at 

0.01 ppm and 0.2 ppm. Average recoveries were generally within 70% to 120%, with standard 

deviations <20%. The following exceptions occurred: method validation orange juice sample 

recoveries at the 0.2 ppm level were 122% ± 19.7% for flazasulfuron and 123% ± 18.4% for 

DTPU; method validation grape RAC sample recoveries at the 0.2 ppm level were 104% ± 21% 

for flazasulfuron and 102% ± 21% for DTPU; method validation raisin sample recoveries at the 

0.01 ppm level were 82% ± 22% for flazasulfuron and 153% ± 35% for DTPU; method 

validation raisin sample recoveries at the 0.2 ppm level were 124% ± 19% for flazasulfuron and 

132% ± 26% for DTPU; and method validation sugarcane bagasse sample recovery at the 0.01 

ppm level was 122% ± 8.2% for flazasulfuron. Apparent residues of flazasulfuron and DTPU 

were <LOQ in control samples of each matrix tested.

HED Conclusions. Adequate methods are available for both enforcing the proposed tolerance 

and for collecting data. 

An adequate residue analytical method using high performance liquid chromatography/tandem 

mass spectrometry with multiple reaction monitoring (HPLC/MS-MS/MRM) (ADME study 

code S09-03106; MRID 48092201) is available for enforcing the proposed tolerances. The 

method underwent a successful independent laboratory validation (ILV) using olives, tomatoes, 

and wheat. The validated limit of quantitation (LOQ) is 0.01 ppm. Radiovalidation is not 

needed since the extraction solvent is the same (acetonitrile:water, 80:20, v/v) in the method 

(MRID 48092201) and in the grape, sugarcane, and tomato metabolism studies (MRIDs 

47939905, 47939906, and 47939907, respectively).

In the field trials and processing studies submitted, residues of flazasulfuron and/or DTPU were 

determined using an adequate HPLC-MS/MS method (CCRL-MTH-045). The method was

adequately validated both prior to and in conjunction with the analysis of the field trial and 

processing study samples. The lowest level of method validation (LLMV) was 0.01 ppm in each 

matrix tested.

Animal

The petitioner did not submit residue analytical methods for livestock. 

HED Conclusions. HED is waiving the requirement for residue analytical methods for livestock 

commodities because tolerances for livestock commodities are not needed.
Page 19 of 33

860.1360 Multiresidue Methods

Flazasulfuron is not listed in the FDA PESTDATA database (Pesticide Analytical Manual, 

Volume I, Appendix I, 3rd edition, 1994, revised October 1999). Additionally, the petitioner did 

not submit multiresidue methods data.

HED Conclusions. The petitioner is required to submit multiresidue methods data since 

tolerances will be established. 

860.1380 Storage Stability

DER References: 47939901.der1 (citrus), 47939902.der1 (grape), 47939903.der (grape), 47939903.der (sugarcane)

ISK Biosciences Corporation has submitted the results of a storage stability study with 

flazasulfuron in grapes. Untreated grape samples from four field trials conducted in France were 

combined to form one homogenous bulk sample and then fortified with flazasulfuron at nominal 

fortification levels of 1.0 ppm and 0.05 ppm. Samples were placed in frozen storage at 

approximately -20oC and analyzed at storage intervals of 0 (Day 0), 1.5 (Day 50), 4 (Day 121), 8 

(Day 237) and 12 months (Day 363). The storage stability data indicate that residues of 

flazasulfuron are stable in grapes stored at approximately -20°C for at least 12 months.

In conjunction with field trials and processing studies, Ishihara Sangyo Kaisha, Ltd. generated 

data demonstrating the frozen storage stability of flazasulfuron and/or DTPU in citrus, grape, and 

sugarcane commodities. The stability of flazasulfuron was determined in oranges, grapes, and 

sugarcane and the stability of DTPU was determined in oranges and grapes. For each 

commodity, control samples were separately fortified with flazasulfuron or DTPU at 

approximately 0.2 ppm and stored under the same conditions as the field trial and processing 

study samples. The fortified stored samples were analyzed along with a control sample and 

freshly fortified control samples of each commodity at the following storage intervals: 0, 32, 92, 

and 183 days for oranges and sugarcane and 0 and 90 days for grapes. The storage stability data 

indicate that residues of flazasulfuron and DTPU are stable in oranges stored at -24 to -7 °C for 

183 days (6 months) and in grapes stored at -23°C to -12°C for 90 days. In sugarcane, 

flazasulfuron is stable at -7 to -22°C for 183 days (6 months).

The storage durations and conditions of samples from the crop field trials and processing studies 

submitted to support these petitions are presented in Table 5. 

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

Matrix Storage 

Temperature 

(°C)

Actual Storage 

Duration

(days)

Interval of Demonstrated Storage Stability (days)

Citrus 

(orange, grapefruit, 

lemon)

-27 to -6 3-125 days

(0.1-4.1 months)

Storage stability data indicate that residues of flazasulfuron and 

metabolite DTPU are stable in/on oranges stored under frozen 

conditions (average of -18oC) for up to 183 days (6.1 months).

Orange Juice -27 to -6 11-12 days 

(<1 month)

No storage stability data are required for processed commodities 

because samples were stored less than 30 days prior to analysis.

Orange Pulp -27 to -6 10-11 days 

(<1 month)
Page 20 of 33

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

Matrix Storage 

Temperature 

(°C)

Actual Storage 

Duration

(days)

Interval of Demonstrated Storage Stability (days)

Orange Oil -27 to -6 10-11 days 

(<1 month)

Grape

-22 to -11 3-85 days

(0.1-2.8 months)

Flazasulfuron: 12 months in/on grapes at approximately -20°C.

DTPU: 90 days (3 months) in/on grapes at an average 

temperature of -19oC.

Raisins -22 to -11 21 days 

(<1 month)

No storage stability data are required for raisins because samples 

were stored less than 30 days prior to analysis.

Grape Juice -22 to -11 36-38 days ( 1.3 

months)

Storage stability data were not provided for grape processed 

commodities. Because the juice and pomace processed 

commodities were only stored for 6 to 8 days longer than the one 

month trigger and because the stability of flazasulfuron was 

demonstrated in the grape RAC, as well as in other RACs 

including sugarcane and citrus, the available storage stability 

data for flazasulfuron are adequate to support the storage 

intervals for the processed commodities.

Grape Pomace -22 to -11 36-38 days ( 1.3 

months)

Sugarcane

-6 to -24 7-111 days

(0.23 – 3.7 months)

Storage stability data collected as part of this study indicate that 

residues of flazasulfuron are stable under frozen storage 

conditions in/on fortified samples of sugarcane for up to 183 

days (6 months) at an average temperature of -18oC.

Sugarcane Bagasse -6 to -24 42 days (1.4 months) Storage stability data were not provided for sugarcane processed 

commodities. Because the processed commodities were only 

stored for 5 to 12 days longer than the one month threshold and 

because the stability of flazasulfuron was demonstrated in the 

sugarcane RAC, as well as in other RACs including grapes and 

citrus, the available storage stability data for flazasulfuron are 

adequate to support the storage intervals for the processed 

commodities.

Sugarcane

Molasses

-6 to -24 41 days (1.3 months)

Sugarcane Refined 

Sugar

-6 to -24 35 days (1.1 months)

HED Conclusions. The available storage stability data are adequate to support the storage 

durations and conditions of citrus, grape, and sugarcane RAC samples. Storage stability data 

were not provided for the processed commodities. As the orange processed commodity samples 

(juice, pulp, and oil) and raisin samples were stored for less than 30 days, no supporting storage 

stability data are required for these commodities. Because the grape juice, grape pomace, 

sugarcane bagasse, molasses, and refined sugar processed commodities were only stored for 5 to 

12 days longer than the one month threshold, and because the stability of flazasulfuron was 

demonstrated in the RACs, the available storage stability data for flazasulfuron are adequate to 

support the storage intervals for the processed commodities.

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.
Page 21 of 33

860.1480 Meat, Milk, Poultry, and Eggs

There are no poultry or swine feedstuffs associated with the subject petition; therefore, data 

requirements pertaining to poultry and swine are not relevant to this petition. The proposed uses 

fall under 40 CFR §180.6(a)(3), i.e., there is no reasonable expectation that finite residues will 

occur in poultry or swine commodities as a result of the proposed uses.

The ruminant feedstuffs associated with the proposed use of flazasulfuron are dried citrus pulp 

and sugarcane molasses. The maximum reasonably balanced dietary burdens (MRBDB) of 

flazasulfuron to ruminants are presented in Table 6. The calculated dietary burdens of 

flazasulfuron are 0.0024 ppm for both beef and dairy cattle. 

Table 6. Livestock Dietary Burdens for Flazasulfuron1

Feedstuff Type Tolerance, 

ppm2 % Dry 

Matter

% Diet Dietary Contributions (ppm) 3

Beef Dairy Poultry Swine Beef Diary Poultry Swine

Dried Citrus Pulp R 0.01 91 10 10 0.0011 0.0011

Untreated R NA NA 5 35 0 0

Sugarcane Molasses CC 0.01 75 10 10 0.0013 0.0013

Untreated CC NA NA 70 35 0 0

Untreated PC NA NA 5 10 0 0

Total Burden 100 100 0.0024 0.0024

1 Potential dietary burdens for livestock were determined using recent Agency guidance on calculating the 

maximum reasonably balanced diets for livestock (Table 1 Feedstuffs, June 2008). 2 The tolerance level for the RAC was used for any associated processed fractions. 3 Contribution = ([tolerance /% DM] x % diet) for beef and dairy cattle; contribution = ([tolerance] x % diet) for 

poultry and swine.

The petitioner did not submit a livestock feeding study. Anticipated secondary residues in beef 

and dairy cattle matrices were estimated using transfer coefficient factors calculated from the 

maximum residues of flazasulfuron observed at the dose level closest to the MRBDB in the goat 

metabolism study. The transfer coefficients (calculated as residue level to feed level ratios) are 

presented in Table 7. The transfer coefficient for each matrix was then used to calculate the 

expected secondary residues by multiplying the transfer coefficient by the calculated MRBDB. 

The expected residues of flazasulfuron are presented in Table 8.

Table 7. Transfer Coefficients in Beef and Dairy Cattle Matrices Based on Flazasulfuron Residues in the 

Goat Metabolism Study.

Matrix Maximum Total Residue 

of Flazasulfuron (ppm)

Feeding Level

(ppm)

Transfer

Coefficient 1

Milk, whole 0.022 11.4 0.00193

Liver 0.352 11.4 0.03088
Page 22 of 33

Table 7. Transfer Coefficients in Beef and Dairy Cattle Matrices Based on Flazasulfuron Residues in the 

Goat Metabolism Study.

Matrix Maximum Total Residue 

of Flazasulfuron (ppm)

Feeding Level

(ppm)

Transfer

Coefficient 1

Kidney 0.166 11.4 0.01456

Muscle 0.049 11.4 0.00430

Fat 0.008 11.4 0.00070

1

 Calculated from the maximum residues observed at the dose level closest to the MRBDB divided by the dose 

level.

Table 8. Expected Secondary Residues of Flazasulfuron in Meat and Milk.

Matrix Dietary Burden

(ppm)

Secondary Residues 1

(ppm)

Recommended Tolerance 

(Current Tolerance)

(ppm)

Beef and Dairy Cattle

Milk, whole 0.0024 4.6E-06 None

Liver 0.0024 7.4E-05 None

Kidney 0.0024 3.5E-05 None

Muscle 0.0024 1.0E-05 None

Fat 0.0024 1.7E-06 None 1

 Calculated from the dietary burden from Table 6 x the transfer coefficient from Table 7.

HED Conclusions. There are no poultry or swine feedstuffs associated with the subject petition;

therefore, data requirements pertaining to poultry and swine are not relevant to this petition. 

The ruminant feedstuffs associated with the proposed uses of flazasulfuron are dried citrus pulp 

and sugarcane molasses. The petitioner did not submit a livestock feeding study. Because of the 

low transfer factors from the goat metabolism study and the low predicted residues in cow milk 

and tissues, HED is waiving the requirement for a cow feeding study. The waiver applies to this 

petition only; if additional uses with associated livestock feed items are proposed in the future, 

then this requirement will need to be re-evaluated.

For all livestock, the proposed uses fall under 40 CFR §180.6(a)(3), i.e., there is no reasonable 

expectation that finite residues will occur in poultry, swine, or ruminant commodities as a result 

of the proposed uses. Therefore, no tolerances are needed for livestock commodities.

860.1500 Crop Field Trials

DER References:

47939901.der1 (citrus)

47939902.der1 (grapes)

47939904.der1 (sugarcane)

Ishihara Sangyo Kaisha, Ltd. has submitted field trial data on citrus (orange, grapefruit and 

lemons), grapes, and sugarcane supporting the proposed uses of flazasulfuron (25% WDG). The 
Page 23 of 33

results from these field trials are discussed below and the residue data are summarized in Table 

9.

Table 9. Summary of Residue Data from Crop Field Trials with Flazasulfuron

Commodity Analyte

Total Applic. 

Rate

(lb ai/A)

PHI 

(days)

Residue Levels (ppm) 1

n Min. Max. HAFT1 Median Mean Std.

Dev.

Citrus (proposed use = 0.15 lb ai/A total application rate, 1-day PHI)

Orange, fruit

Flazasulfuron 

(parent) 0.154 – 0.159

1 24 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

29-30 24 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

DTPU 0.154 – 0.159

1 24 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

29-30 24 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

Grapefruit, 

fruit

Flazasulfuron 

(parent) 0.153 – 0.161

1 12 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

28-30 12 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

DTPU 0.153 – 0.161

1 12 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

28-30 12 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

Lemon, fruit

Flazasulfuron 

(parent) 0.154 – 0.156

1 8 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

30 8 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

DTPU 0.154 – 0.156

1 8 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

30 8 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

Grapes (proposed use = 0.15 lb ai/A total application rate, 75-day PHI)

Grapes, fruit

Flazasulfuron 

(parent) 0.149-0.158 74-77 24 <LOQ (ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) -

DTPU 0.149-0.158 74-77 24 <LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

Sugarcane (proposed use = 0.15 lb ai/A total application rate, 180-day PHI)

Sugarcane Flazasulfuron 

(parent) 0.152-0.164 179-180 16 <LOQ (ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND)

<LOQ 

(ND) --

1 The LOQ is 0.010 ppm. The calculated LOD for flazasulfuron is 0.003 ppm.

Citrus

47939901.der1

Ishihara Sangyo Kaisha, Ltd. has submitted crop field trial data for flazasulfuron in/on orange, 

grapefruit, and lemon, the representative commodities of the citrus fruit group 10. Twenty-three 

citrus crop field trials were conducted in the U.S. Twelve orange field trials in Zones 3 (FL; 8 

trials), 6 (TX; 1 trial), and 10 (CA; 3 trials), six grapefruit field trials in Zones 3 (FL; 3 trials), 6 

(TX; 1 trial), and 10 (CA; 2 trials), and five lemon field trials in Zones 3 (FL; 1 trial) and 10 

(CA; 4 trials) were conducted during the 2008 growing season. The lemon field trial in Zone 3 

(Fort Pierce, FL) was terminated due to the presence of citrus canker. 
Page 24 of 33

Each citrus fruit field site included one untreated plot and one treated plot. At each plot, two soil 

applications of a 25% water dispersible granular (WDG; Flazasulfuron 25 WG) formulation of 

flazasulfuron were made to the ground at the base of the test crops at 0.075-0.083 lb ai/A per 

application, with 95- to 308-day retreatment intervals, for a total seasonal rate of 0.153-0.161 lb 

ai/A (approximately 1x the proposed seasonal rate). Applications were made using ground 

equipment with spray volumes of 20 to 30 gal water/A. An adjuvant was included in the spray 

mixture at all test locations. Samples of commercially mature citrus fruits (oranges, grapefruit, 

and lemons) were collected for each trial at preharvest intervals (PHIs) of 1 day and 30 days. 

Additional samples (oranges, grapefruit, and lemons) were collected from three CA sites at PHIs 

of 10 and 20 days to evaluate residue decline.

At one orange test site, an additional plot received two applications at an exaggerated rate of 

0.771-0.772 lb ai/A per application for a total rate of 1.543 lb ai/A (10x the proposed seasonal 

rate) to generate samples for processing. Refer to the processing DER for MRID 47939901 

(47939901.der2).

Samples of citrus fruit were analyzed for total residues of flazasulfuron and DTPU using Central 

California Research Laboratories, Inc., “Analytical Method for Determination of SL-160 and Its 

Metabolite in Soil” (CCRL-MTH-045), using HPLC-MS/MS. This method is acceptable for 

data collection based on adequate concurrent method recovery data. The limit of quantitation 

(LOQ), defined as the lowest level of method validation (LLMV) at which acceptable recovery 

can be achieved, was 0.01 ppm for each analyte. The calculated limit of detection (LOD) for 

flazasulfuron and DTPU in all products was 0.003 ppm based on the lowest standard of the 

calibration curve.

Samples were stored frozen for up to 125 days (4.1 months) prior to analysis. To support this 

storage interval, a concurrent storage stability study was conducted in conjunction with the 

analysis of field trial samples. Samples of orange fruit were fortified with flazasulfuron and 

DTPU, each at 0.2 ppm. Residues were stable in frozen orange fruit for 183 days. 

After two applications of Flazasulfuron 25 WG were made to the ground/weeds below the base 

of citrus trees at total rate of 0.153-0.161 lb ai/A, there were no detectable residues of 

flazasulfuron or DTPU in/on any citrus samples. A decline curve could not be established 

because no residues were detected in the residue decline samples.

Grapes

47939902.der1

Ishihara Sangyo Kaisha, Ltd. has submitted crop field trial data for flazasulfuron in/on grapes. 

Twelve field trials were conducted in the U.S. in the 2008 growing season, encompassing Zones 

1 (NY, 1 trial; PA; 1 trial), 10 (CA, 8 trials), and 11 (OR, 1 trial; ID, 1 trial). Each trial included 

one untreated plot and one treated plot. At each treated plot, two soil applications of a 25% 

water-dispersible granular (WDG/WG) formulation of flazasulfuron (Flazasulfuron 25 WG) 

were made to the ground at the base of the test crops at 0.085 to 0.091 lb ai/A for the first 

application and 0.064 to 0.068 lb ai/A for the second application, with 14- to 118-day retreatment 

intervals. The total seasonal rate was 0.149-0.158 lb ai/A (approximately 1x the proposed 
Page 25 of 33

seasonal rate). Applications were made using ground equipment with spray volumes of 20 to 38 

gal water/A. An adjuvant was included in the spray mixture at all test locations. Samples of 

grapes were collected for each trial at a preharvest interval (PHI) of 74 to 77 days. Additional 

samples were collected from one CA site (Site 09) at PHIs of 55, 65, 75, and 85 days to evaluate 

residue decline.

At one CA test site, an additional plot received two applications at an exaggerated rate of 0.662-

0.888 lb ai/A per application for a total rate of 1.55 lb ai/A (10x the proposed seasonal rate) to 

generate samples for processing. Refer to the processing DER for MRID 47939902

(47939902.der2).

Samples of grapes were analyzed for residues of flazasulfuron and DTPU using Central 

California Research Laboratories, Inc., “Analytical Method for Determination of SL-160 and Its 

Metabolite in Soil” (CCRL-MTH-045), using HPLC-MS/MS. This method is acceptable for 

data collection based on adequate concurrent method recovery data. The limit of quantitation 

(LOQ), defined as the lowest level of method validation (LLMV) at which acceptable recovery 

can be achieved, was 0.01 ppm for each analyte. The calculated limit of detection (LOD) for 

flazasulfuron and DTPU in all products was 0.003 ppm based on the lowest standard of the 

calibration curve.

Samples were stored frozen for up to 85 days (2.8 months) prior to extraction. Samples were 

analyzed within one day of extraction. To support this storage interval, a concurrent storage 

stability study with DTPU was conducted in conjunction with the analysis of field trial samples. 

Samples of grapes were fortified with DTPU at 0.2 ppm. DTPU residues were stable in frozen 

grapes for 90 days. The storage stability of flazasulfuron in grapes was investigated in a separate 

study (MRID 47939903; refer to 47939903.der) in which samples were fortified with 

flazasulfuron at nominal fortification levels of 1.0 ppm and 0.05 ppm. The storage stability data 

indicate that residues of flazasulfuron are stable at approximately -20°C for at least 12 months in 

grapes. Adequate storage stability data for flazasulfuron and DTPU are available to support the 

storage conditions and durations for grapes in the field study. 

After two applications of Flazasulfuron 25 WG were made to the ground at the base of the grape 

vines at a total rate of 0.149-0.158 lb ai/A, there were no detectable residues of flazasulfuron or 

DTPU in/on any grape samples. A decline curve could not be established because no residues 

were detected in the residue decline samples.

Sugarcane

47939904.der1

Ishihara Sangyo Kaisha, Ltd. has submitted field trial data for flazasulfuron in/on sugarcane. 

Eight field trials were conducted in the U.S. during the 2008 growing season, encompassing 

Zones 3 (FL, 3 trials), 4 (LA, 3 trials), 6 (TX, 1 trial), and 13 (HI, 1 trial). One treated plot and 

one untreated control plot were established at each trial site. For each trial, one application of 

Flazasulfuron (SL-160) 25 WG (a 25.85% w/w, water-dispersible granule) was made to the 

ground at the base of the sugarcane plants using CO2 backpack sprayers at a target rate of 0.15 lb 

ai/A. Actual treatment rates ranged from 0.152 to 0.164 lb ai/A (approximately 1x the proposed 
Page 26 of 33

seasonal rate). Spray volumes ranged from 20 to 31 gal/A (GPA). Sugarcane samples were 

collected at pre-harvest intervals (PHIs) of 179-180 days. Additional samples were collected at 

one site (Trial 02) at PHIs of 160, 170, 180, and 190 days to establish a decline curve. 

At one site (Trial 03), an additional plot was treated at an exaggerated rate of 1.514 lb ai/A (10x 

the proposed seasonal rate) to generate samples for processing. Refer to the processing DER for 

MRID 47939904.

Sugarcane samples were analyzed for residues of flazasulfuron using Central California 

Research Laboratories, Inc., “Analytical Method for Determination of SL-160 and Its Metabolite 

in Soil” (CCRL-MTH-045), using HPLC-MS/MS. This method is acceptable for data collection 

based on adequate concurrent method recovery data. The limit of quantitation (LOQ), defined as 

the lowest level of method validation (LLMV) at which acceptable recovery can be achieved, 

was 0.01 ppm and the calculated limit of detection (LOD) was 0.003 ppm based on the lowest 

standard of the calibration curve.

Sugarcane samples were stored frozen for up to 91 days (3 months). All sample extracts were 

analyzed within 1 day of extraction. To support this storage interval, concurrent storage stability 

data were submitted with this study. Samples of sugarcane were fortified with flazasulfuron at 

0.2 ppm. The storage stability data indicate that residues of flazasulfuron in sugarcane are stable 

for up to 183 days (6 months) of freezer storage at -7 to -22°C (average of -18°C).

Following a single application of Flazasulfuron 25 WG at a target application rate of 0.15 lb 

ai/A, there were no detectable residues of flazasulfuron in/on any sugarcane samples. A decline 

curve could not be established because no residues were detected in the decline study samples.

HED Conclusions: The number and locations of crop field trials are in accordance with OPPTS 

Guideline 860.1500 for grapes and sugarcane. For citrus, one lemon field trial is lacking 

because a lemon field trial in Florida (Region 3) was terminated due to the presence of citrus 

canker. An additional lemon field trial will not be required because data from the remaining 

field trials will sufficiently represent residues likely to be seen. All trials reflect the proposed use 

pattern; however, for the sugarcane trials, the maximum seasonal application rate was applied in 

a single application. The maximum single application rate on the label for sugarcane is 

approximately 3.3x less than the maximum seasonal application rate. The RTI on the label is 

only 14 days. Data from these trials are sufficient; flazasulfuron residues were all <LOQ (<0.01 

ppm).

Pending the requested revisions to the Section B/label, the available field trial data will support 

the proposed tolerance of 0.01 ppm for residues of flazasulfuron in/on citrus, grapes, and 

sugarcane. The tolerance spreadsheet in the Agency’s Guidance for Setting Pesticide Tolerances 

Based on Field Trial Data was not utilized for determining appropriate tolerance levels because 

all of the treated samples bore residues below the LOQ.
Page 27 of 33

860.1520 Processed Food and Feed

DER References: 47939901.der2 (citrus), 47939902.der2 (grapes), 47939904.der2 (sugarcane)

Ishihara Sangyo Kaisha, Ltd. has submitted processed food and feed data on citrus (oranges), 

grapes, and sugarcane supporting the proposed uses of flazasulfuron (25% WDG). The results 

from these field trials are discussed below and the residue data are summarized in Table 10.

Table 10. Residue Data from Processing Studies with Flazasulfuron.

RAC Processed 

Commodity

Total Rate

(lb a.i./A)

PHI 

(days)

Residues (ppm)1 Processing Factor2,3

Flazasulfuron DTPU Flazasulfuron DTPU

Orange, 

fruit

Fruit (RAC) 1.54 1 ND, ND, ND ND, ND, ND -- --

Juice ND, ND ND, ND NC NC

Dried pulp ND, ND ND, ND NC NC

Oil ND, ND ND, ND NC NC

Grape RAC

1.55 1

ND, ND, ND ND, ND, ND -- --

Raisin ND, ND 0.0109, 0.0102

Avg. 0.0106 NC 1.1x4

Juice ND, ND ND, ND NC NC

Pomace ND, ND <0.01, <0.01

Avg. <0.01 NC NC

Sugarcane RAC 1.51 180 ND, ND Not Analyzed -- Not Analyzed

Bagasse ND, ND Not Analyzed NC Not Analyzed

Molasses ND, ND Not Analyzed NC Not Analyzed

Refined Sugar ND, ND Not Analyzed NC Not Analyzed 1 ND = Not detected. The LOD for each analyte was <0.003 ppm. The LOQ was 0.01 ppm.

2

Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in RAC collected 

for processing]. The LOQ was used when residues were <LOQ in calculations. 3 Processing factors could not be calculated (NC) because residues were below the LOQ in both the RAC and processed 

commodities.

4 This value is not statistically significant to two significant figures. Also, this value is based on the LOQ of 0.01 ppm. If based 

on the LOD of 0.003 ppm, it would be 3.5x.

Citrus

47939901.der2

Ishihara Sangyo Kaisha, Ltd. has submitted a processing study for flazasulfuron on orange. In 

one field trial conducted in CA during the 2008 growing season, two applications of the 25% 

water-dispersible granular (WDG/WG) formulation of flazasulfuron were applied to the soil at 

the base of orange trees at 0.077 lb ai/A per application, for a total rate of 1.54 lb ai/A (10x the 

proposed seasonal rate). The first application was made at bud swell and the second application 

was made at maturity. Ground equipment was used with spray volumes of 29 gal water/A. An 

adjuvant was included in the spray mixtures. Mature orange fruits were harvested one day after 

the second application.

Samples of orange fruit and processed commodities (juice, dried pulp, and oil) were analyzed for 

residues of the parent compound, flazasulfuron, and metabolite DTPU following Central 

California Research Laboratories, Inc., “Analytical Method for Determination of SL-160 and Its 

Metabolite in Soil” (CCRL-MTH-045), included in the study report as part of Appendix 25, 

Protocol and Amendments. The validated limit of quantitation (LOQ) for flazasulfuron and 
Page 28 of 33

DTPU was 0.01 ppm for each analyte. The limit of detection (LOD) for flazasulfuron and DTPU 

in all products was 0.003 ppm based on the lowest standard of the calibration curve. The method 

was adequate based on acceptable concurrent recoveries.

Residues of flazasulfuron and DTPU were each nondetectable (<0.003 ppm) in/on all orange 

RAC samples. Following processing, residues of flazasulfuron and DTPU were also 

nondetectable in orange juice, dried pulp, and oil. Because residues were nondetectable in the 

RAC and all processed fractions, no processing factors could be calculated.

The theoretical concentration factors based on separation into components are 3.3x for citrus 

peel, 1000x for citrus oil, and 2x for juice and dehydrated pulp (OPPTS 860.1520, Table 3).

Grapes

47939902.der2

Ishihara Sangyo Kaisha, Ltd. has submitted a processing study for flazasulfuron on grapes. In 

one field trial conducted in CA during the 2008 growing season, two applications of the 25% 

water-dispersible granular (WDG/WG) formulation of flazasulfuron were applied to the soil at 

the base of the grape vines at 0.888 lb ai/A for the first application and 0.662 lb ai/A for the 

second application, for a total rate of 1.55 lb ai/A (10x the proposed seasonal rate). Applications 

were made using ground equipment at a spray volume of 25 gal/A of water; an adjuvant was 

included in the spray mixture for the second application. Grape samples were harvested 65 days 

after the second application.

Samples of grape and processed commodities (raisin, juice, and pomace) were analyzed for 

residues of the parent compound, flazasulfuron, and metabolite DTPU following Central 

California Research Laboratories, Inc., “Analytical Method for Determination of SL-160 and Its 

Metabolite in Soil” (CCRL-MTH-045), using HPLC-MS/MS. The validated limit of quantitation 

(LOQ) for flazasulfuron and DTPU was 0.01 ppm for each analyte. The limit of detection 

(LOD) for flazasulfuron and DTPU in all matrices was 0.003 ppm based on the lowest standard 

of the calibration curve. The method was adequate based on acceptable concurrent recoveries.

Residues of flazasulfuron and DTPU were nondetectable (<0.003 ppm) in/on all grape RAC 

samples. Following processing, residues of flazasulfuron were also nondetectable in grape juice, 

pomace and raisins; therefore, no processing factors could be calculated for flazasulfuron. 

Residues of DTPU were nonquantifiable in grape juice and pomace, but were slightly above the 

LOQ in raisins (average of 0.0106 ppm). Processing factors could not be calculated for DTPU in 

grape juice or pomace. In raisins, the estimated concentration factor for DTPU is 1.1x. The 

theoretical concentration factor based on separation into components is 1.2x for grape juice 

(OPPTS 860.1520, Table 3). For raisins, the theoretical concentration factor based on loss of 

water is 4.7x (OPPTS 860.1520, Table 2).
Page 29 of 33

Sugarcane

47939904.der2

Ishihara Sangyo Kaisha, Ltd. has submitted a sugarcane processing study for flazasulfuron. In 

one trial conducted in Cheneyville, Louisiana during the 2008 growing season, a single 

application of Flazasulfuron (SL-160) 25 WG (a 25.85% w/w, water-dispersible granule) was 

made to the ground at the base of sugarcane plants at a rate of 1.51 lb ai/A/application (10x the 

proposed seasonal rate). The application was made using a CO2 backpack sprayer at a spray 

volume of 22.6 gallons per acre. An adjuvant was added to the spray mixture. Bulk sugarcane 

samples were harvested at a pre-harvest interval (PHI) of 180 days and processed into bagasse, 

molasses, and refined sugar using procedures that simulated commercial processing. 

Sugarcane RAC, bagasse, molasses, and refined sugar were analyzed for residues of 

flazasulfuron using Central California Research Laboratories, Inc., “Analytical Method for 

Determination of SL-160 and Its Metabolite in Soil” (CCRL-MTH-045), using HPLC-MS/MS. 

This method is acceptable for data collection based on adequate concurrent method recovery 

data. The limit of quantitation (LOQ), defined as the lowest level of method validation (LLMV) 

at which acceptable recovery can be achieved, was 0.01 ppm in each matrix. The calculated 

limit of detection (LOD) for flazasulfuron was 0.003 ppm based on the lowest standard of the 

calibration curve.

After one application of flazasulfuron at an exaggerated rate of 1.51 lb ai/A/application, 

flazasulfuron (parent) residues in/on treated RAC (sugarcane) used for processing were 

nondetectable (<0.003 ppm). Following processing, residues of flazasulfuron (parent) were also 

nondetectable in bagasse, molasses, and refined sugar. Because residues were nondetectable in 

the RAC and all processed commodities, no processing factors could be calculated. 

HED Conclusions: Under the conditions and parameters used in the study, the data are classified 

as scientifically acceptable. Processing factors for parent could not be calculated for any of the 

processed commodities because no quantifiable residues of flazasulfuron (parent) occurred. 

Therefore, separate tolerances are not required for orange dried pulp, orange juice, orange oil, 

grape juice, raisins, sugarcane refined sugar, or molasses.

860.1650 Submittal of Analytical Reference Standards

An analytical standard for flazasulfuron, with an expiration date of February 2012, is currently 

available in the EPA National Pesticide Standards Repository (personal communication with 

Theresa Cole, ACB, 9/27/10).

860.1850/860.1900 Confined/Field Accumulation in Rotational Crops

There are no rotational crop data requirements associated with the use on citrus or grapes 

(OPPTS 860.1850). The rotational crop guidelines are applicable for sugarcane; however, 

rotational crop data have not been submitted. The proposed label for sugarcane requires a 12-

month interval between the last application and the planting of the rotational crop. 
Page 30 of 33

HED Conclusions: While HED considers the 12-month plantback restriction for sugarcane on 

the proposed label to be adequate for conditional registration of flazasulfuron based on the fact 

that no detectable residues were found in the primary crops, a confined rotational crop study is 

required to support permanent registration of sugarcane. Depending on the results of the 

confined rotational crop study, a study to determine field accumulation in rotational crops may 

be required.

860.1550 Proposed Tolerances

The ROCKS determined on 2/15/11 that the residue of concern for plants for the tolerance 

expression is parent. 

No tolerances are needed for rotational crops, ruminants, or poultry.

Adequate field trial data are available for the RACs of citrus, grapes, and sugarcane. 

The tolerance spreadsheet in the Agency’s Guidance for Setting Pesticide Tolerances Based on 

Field Trial Data was not utilized for determining an appropriate tolerance level for the RACs of 

citrus, grapes, and sugarcane because all of the treated samples bore residues below the LOQ.

Tolerances for the processed commodities of citrus (orange juice, pulp and oil), sugarcane 

(molasses and refined sugar) or grape (grape juice and raisin) are not needed for the purpose of 

this petition based on the results of processed food and feed trials which showed that residues of 

flazasulfuron (parent) were below the LOQ (<0.01 ppm). 

A tolerance summary for flazasulfuron is presented in Table 11. 

Table 11. Tolerance Summary for Flazasulfuron.

Commodity Proposed Tolerance

(ppm)

Recommended Tolerance

(ppm)

Comments; Correct 

Commodity Definition

Citrus 0.01 0.01 Fruit, citrus, group 10-

10

Grapes 0.01 0.01 Grape

Sugarcane 0.01 0.01

There are no Codex, Canadian, or Mexican MRLs/tolerances established for residues of 

flazasulfuron in crop or livestock commodities. Therefore, there are no issues regarding

international harmonization raised by this action. An International Residue Limit (IRL) status 

sheet is appended to this document.

HED Conclusion. The petitioner must submit a revised Section F to propose tolerances which 

reflect the correct commodity definitions as specified in Table 11.
Page 31 of 33

References

DP#: D302103

Subject: FEE. Secondary Product Chemistry Review on Flazasulfuron Technical 

From: S. Mathur

To: C. T-Sen/J. Tompkins

Date: 2/26/07

MRID#: 46220905

DP#: None

Subject: Flazasulfuron; Report of the Residues of Concern Knowledgebase Subcommittee 

(ROCKS)

From: Edward J. Scollon

To: Jack Arthur

Date: 5/12/08

MRID#: None

Attachments:

Appendix 1: International Residue Limits Status Sheet

Appendix 2: Chemical Names and Structures Table
Page 32 of 33

APPENDIX 1

International Residue Limits 

Flazasulfuron (PC Code 119011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.xxx:

Plant/Livestock: N-[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]-3-

(trifluoromethyl)-2-pyridinesulfonamide

None None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Fruit, citrus, group 10-10 0.01

Grape 0.01

Sugarcane 0.01

Completed: M. Negussie; 1/12/2010

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

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

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.
Page 33 of 33

APPENDIX 2

Chemical Names and Structures for Flazasulfuron and its Metabolites

Common name/code Chemical name Chemical structure

Flazasulfuron/SL-160 N-[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]-3-

(trifluoromethyl)-2-

pyridinesulfonamide

ADMP 2-amino-4,6-dimethoxypyrimidine

DTPU N-(4,6-dimethoxy-2-pyrimidinyl)-N-

[3-(trifluoromethyl)-2-pyridinyl]urea

DTPP 4,6-dimethoxy-N-[3-

(trifluoromethyl)-2-pyridinyl]-2-

pyrimidinamine

HTPP 6-methoxy-2-[[3-(trifluoromethyl)-2-

pyridinyl]amino]-4-pyrimidinol

TPSA 3-(trifluoromethyl)-2-

pyridinesulfonamide