Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDE

AND TOXIC SUBSTANCES

MEMORANDUM

Date: February 24, 2010

SUBJECT: Cyazofamid. Tolerance Petition for Uses on Brassica (Cole) Leafy Vegetables 

Crop Group 5, Turnip Greens, Spinach, and Hops. Summary of Analytical 

Chemistry and Residue Data.

PC Code: 085651 DP Barcode: D371162

Decision No.: 420982 Registration No.: EPA Reg. Nos. 71512-2 & 

71512-3 

Petition No.: 9E7615 Regulatory Action: Section 3 Registration 

Risk Assessment Type: NA Case No.: NA

TXR No.: NA CAS No.: 120116-88-3

MRID No.: See MRID Summary Table 40 CFR: 180.601

Ver.Apr.08

FROM: Amelia M. Acierto, Chemist

Risk Assessment Branch III

Health Effects Division (7509P)

THROUGH: Stephen Funk, Senior Science Advisor

Risk Assessment Branch III

Health Effects Division (7509P)

TO: Barbara Madden RM, 05

Risk Integration, Minor Use and Emergency Response Branch (RIMUERB)

 Registration Division (7505P)

MRID Summary Table

MRID No. Study Type Comments

47870701 860.1500 Broccoli New DER; 47870701.der.doc

47870702 860.1500 Cabbage New DER; 47870702.der.doc

47870703 860.1500 mustard greens New DER; 47870703.der.doc

47870704 860.1500 spinach New DER; 47870704.der.doc

47870705 860.1500 hops New DER; 47870705.der.doc
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Executive Summary

The Interregional Research Project No. 4 (IR-4), State Agricultural Experiment Station, Rutgers, 

The State University of New Jersey, New Brunswick, New Jersey 08902, on behalf of the IR-4 

Project and the Agricultural Experiment Stations of Florida, Oklahoma, New York, California, 

Georgia, North Carolina, Oregon, Virginia, Tennessee, Ohio, and Washington, has submitted a

petition proposing the establishment of permanent tolerances for the combined residues of the 

fungicide cyazofamid [4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-

sulfonamide] and its metabolite CCIM [4-chloro-5-(4-methylphenyl)-1H-imidazole-2-

carbonitrile] in/on the following raw agricultural commodities (RACs):

Brassica, Head and Stem, subgroup 5A ....................................... 1.2 ppm

Brassica, Leafy Greens, subgroup 5B ...........................................12.0

Turnip greens ................................................................................12.0

Spinach ......................................................................................... 9.0

Hops ................................................................ ........................... 10.0

This petition is associated with a FIFRA Section 3 request to amend the registration to add to the 

labels the minor uses in/on the listed crops for Cyazofamid Technical (EPA Reg. No. 71512-2) 

and for the end-use product, Ranman®400 SC (EPA Reg. No. 71512-3), a suspension 

concentrate (SC) formulation containing 3.33 lb ai/gal. 

Ranman®400SC is the product proposed for minor uses on Brassica crop subgroup 5A and 5B

as a single post transplant soil drench applied to the base of the plants at the rate of 0.118 lb ai/A

followed by multiple (5) foliar applications at a target rate of 0.072 lb ai/A/application with a 

maximum seasonal foliar application rate of 0.360 lb ai/A or a total applied rate of 0.478 lb 

ai/A/season (1 soil drench + 5 foliar applications). Soil drench application was not proposed for 

spinach or hops. The formulated product is proposed for use on spinach as five foliar sprays at 

the target rate of 0.072 lb ai/A/application with a maximum seasonal rate of 0.36 lb ai/A and six 

foliar applications on hops at the target rate of 0.072 lb ai/A/application with a maximum 

seasonal rate of 0.426 lb ai/A. Re-treatment intervals (RTIs) of 7 to 10 days are proposed for all 

the crops, starting when disease is first detected or when weather or disease pressure is expected 

to initiate a disease epidemic. Preharvest intervals (PHIs) are proposed at 0 day for the Brassica

vegetables and spinach and 3 days for hops. Except for hops, Silwet L-77, a non-ionic

organosilicone surfactant, is recommended to be tank mixed at a 4:3 ratio for all foliar sprays.

Tolerances have been established in 40 CFR §180.601(a) for the combined residues of 

cyazofamid and CCIM expressed as cyazofamid in/on carrot, roots at 0.09 ppm, okra at 0.40 

ppm, potato at 0.02 ppm, vegetable, cucurbit, group 9 at 0.10 ppm, and vegetable, fruiting, group 

8 at 0.40 ppm. In addition, tolerances with regional registrations are established in 40 CFR 

§180.601(c) in/on grape at 1.5 ppm.

The nature of the residues in crops is adequately understood for the purposes of this petition 

based on the available grape, potato, tomato, goat and hen metabolism studies. The metabolism 

studies indicate that several of the metabolites resulting from the cyazofamid metabolism are 

common to both plants and livestock. HED concluded that, for risk assessment and tolerance 

expression, cyazofamid and CCIM are the residues of concern in both plants and livestock. 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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However, based on available ruminant metabolism studies in goats, HED required that for future 

cattle feeding studies, cyazofamid, CCIM, CCBA [4-(4-chloro-2-cyanoimidazole-5-yl)benzoic 

acid] and CCBA-cysteine conjugates should be analyzed (PP# 1F6305, D285680, Amelia M. 

Acierto, 2/20/2004).

An acceptable analytical method is available for enforcement purposes. The Agency finds that 

the FDA Multi-Residue Method, Protocol D (without cleanup) meets the requirement of the 

Residue Chemistry Test Guideline 860.1360 to enforce tolerances for non-fatty commodities and 

recommends its use as the enforcement method. In addition, an acceptable high performance 

liquid chromatography/ultraviolet detector (HPLC/UV) method is available for use as a single 

analyte confirmatory method. 

An adequate data collection method derived from “Independent Laboratory Validation of the 

Residue Method for IKF-916 and CCIM in Tomatoes”, Document Number 013033-0, Pyxant 

Labs Inc, is available. Quantification of the residues of cyazofamid and CCIM is achieved by

liquid chromatography with tandem mass spectrometric detection (LC/MS/MS). The calculated 

LOQ and LOD were 0.03 ppm and 0.01 ppm, respectively, for cyazofamid and 0.02 ppm and 

0.006 ppm, respectively, for CCIM. The lowest level of method validation (LLMV) was 0.05 

ppm for both cyazofamid and CCIM.

The crop field trial data submitted are adequate to support the proposed new minor uses of 

cyazofamid in/on Brassica vegetables, spinach and hops. The combined residues of cyazofamid 

and CCIM following one post transplant soil drench plus foliar applications (total rate of 0.479-

0.552 lb ai/A/season), ranged from 0.185-0.915 ppm for brocolli, 0.125-0.895 ppm for cabbage 

and 6.86 ppm for mustard greens. In spinach, residues following a total application of 0.347-

0.366 lb ai/A/season ranged from 1.45-6.62 ppm. In hop cones, residues following application of 

0.425-0.443 lb ai/A/season ranged from 2.92-7.03 ppm. Residue decline data show that 

cyazofamid and CCIM residues in mustard greens and spinach decreased with increasing preharvest intervals.

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

samples of cabbage, mustard greens, spinach and hops. Although the concurrent recoveries were 

acceptable for broccoli, the storage stability data were erratic, which, according to the petitioner 

may have been due to the spiking solution that appeared to have degraded (separated) during 

frozen storage. The petitioner proposed to use the available storage stability data on tomatoes,

potatoes and grapes and the current data on cabbage to support the storage stability of the 

residues of cyazofamid and CCIM for broccoli.

The tolerance spreadsheet calculations indicate that the proposed tolerances for the combined 

residues of cyazofamid and CCIM are appropriate.

Canada has established maximum residue limits (MRL) for residues of cyazofamid in/on several 

commodities, but has not established maximum residue limits for the commodities of this 

petition. No maximum residue limits (MRLs) for residues of cyazofamid have been 

establishedby the Codex Alimentarius Commission. 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for cyazofamid and concludes that provided 

the forthcoming Human Health Risk Assessment does not identify any risks of concern, there are 

no residue chemistry issues that would preclude granting the requested Section 3 registration for 

the proposed minor uses and the establishment of tolerances for the combined residues of 

cyazofamid and its metabolite CCIM in/on the commodities listed below. 

(a) General. Tolerances are established for residues of the fungicide cyazofamid, 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 the sum of

4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its 

metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the 

stoichiometric equivalent of cyazofamid, in or on the commodity.

Brassica, Head and Stem, subgroup 5A ....................................... 1.2 ppm 

Brassica, Leafy Greens, subgroup 5B ...........................................12.0

Turnip greens ................................................................................12.0 

Spinach ......................................................................................... 9.0

Hops ................................................................ ........................... 10.0

Note to PM: HED recommends modification of the tolerance expressions for cyazofamid 

according to the new compliance/measurement policy (Interim Guidance on Tolerance 

Expressions, Steve Knizner, May 27, 2009). The tolerance definition entry in 40 CFR 180.601 

should be revised as shown above.

A human health risk assessment is forthcoming.

Background

Cyazofamid is a broad-spectrum fungicide active against oomycete fungi (such as Phytophthora, 

Plasmopara, Pseudoperonospora, and Pythium) and Plasmodiophoromycetes (Plasmodiospora

brassicae). It inhibits all stages of fungal development in the life cycle of Phytophthora

infestans which causes late blight disease in potatoes and tomatoes, and inhibits the germination 

and formation of zoosporangia, germination of cytospores, zoospore mobility, and mycelial 

growth. It controls downy mildew in cucurbit vegetables and grapes. 

Cyazofamid is the active ingredient in the end-use product (EUP) Ranman 400 SC, a suspension 

concentrate containing 3.33 lb ai/gal. Ranman 400 SC is proposed for minor use in the control of 

club root (Pasmodiophora brassiceae) and downy mildew (Peronospora parasitica) in Brassica

vegetables, white rust (Albugo occidentalis) disease in spinach; and downy mildew 

(Pseudoperonospora humuli) in hops. 

The chemical structure, nomenclature and physicochemical properties of the technical grade of 

cyazofamid and its metabolite CCIM, are shown in Tables 1 and 2.
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Table 1. Test Compound Nomenclature.

Compound Chemical Structure

N

N

H3C

Cl

CN

SO2N(CH3)

2

Common name Cyazofamid

Company experimental name N/A

IUPAC name 4-chloro-2-cyano-N, N-dimethyl-5-p-tolylimidazole-1-sulfonamide

CAS name 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide

CAS registry number 120116-88-3

End-use product (EP) Ranman® 400SC Agricultural Fungicide (EPA Reg. No. 71512-3)

Compound Chemical Structure of metabolite

N

H

N

H3C

Cl

CN

Common name CCIM

IUPAC name 4-chloro-5-p-tolylimidazole-2-carbonitrile

CAS name 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile

Table 2. Physicochemical Properties of the Technical Grade Cyazofamid.

Parameter Value Reference

Melting point (°C) 152.7 PMRA Regulatory Note REG2006-

05 on Cyazofamid, 12/6/06

pH 4.9 e-Pesticide Manual, 13th Edition

Density at 20 °C (g/mL) 1.446
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Table 2. Physicochemical Properties of the Technical Grade Cyazofamid.

Parameter Value Reference

Water solubility (at 20 °C) pH Solubility (mg/L) REG2006-05

5

7

9

0.121

0.107

0.109

Solvent solubility (at 21.2°C) Solvent Solubility (g/L)

Acetone

Ethyl acetate

Methanol

Dichloromethane

Toluene

Hexane

n-Octanol

Acetonitrile

2-Propanol

43.1

16.19

1.74

94.82

6.0

0.03

0.04

29.446

0.43

Vapor pressure at 25°C <1.33 x 10-5Pa

Dissociation constant (pKa) Does not dissociate in water. No pKain 

the pH range of 2-12.

Octanol/water partition 

coefficient 

LogKOW = 3.2

KOW = 1.585 x 103

UV/visible absorption spectrum pH Λmax (nm)

2

7

10

285

279

287

860.1200 Directions for Use

IR-4 has submitted a proposed supplemental label for the product to be used on crops: (Ranman®

400SC, EPA Reg. No. 71512-3) a suspension concentrate formulation containing 3.33 lb ai/gal. 

The proposed use directions for Ranman®400SC is summarized in Table 3. 

Table 3. Summary of Directions for Use of Ranman® 400SC (EPA Reg. No. 71512-3)

Applic. 

Timing, Type, 

and Equip.

Applic. Rate 

fl oz

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

fl oz (lb ai/A)

TRI

(days)

PHI

(days)

Use Directions and 

Limitations

Crop Group 5, Brassica (Cole) Leafy vegetables: Broccoli; Chinese broccoli (gai lon); broccoli raab 

(rapini); Brussels sprouts; cabbage; Chinese cabbage (bok choy); Chinese cabbage (napa); Chinese mustard 

(gai choy); cauliflower; cavalo broccolo; collards; kale; kohlrabi; mizuna; mustard greens; mustard 

spinach; rape greens; turnip greens 1,2,3,4

Transplant Soil 

Drench (for 

control of Club 

root disease) 2

12.9 to 25.75

(0.333-0.665/

100 gal)

1 25.75

(0.665 lb 

ai/100 gal)

Soil drench immediately after 

transplant: make a single 

application within the rate 

range listed and apply 1.7 fl.

oz per plant as transplant 

water. 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Table 3. Summary of Directions for Use of Ranman® 400SC (EPA Reg. No. 71512-3)

Foliar (For the 

control of 

Downy mildew 

disease) 3

2.75

(0.072)

5 13.75

(0.36)

7 to 10 0 Begin spray when disease is 

first seen or weather and 

downy mildew disease 

pressure are expected to 

initiate a disease epidemic. 

Use longer interval for 

preventive or low disease 

pressure.

Do not apply more than six (1 

soil + 5 foliar) applications of 

RANMAN 400SC per 

season.

Spinach

Foliar (For 

control of 

white rust 

disease) 5

2.1 to 2.75 

(0.054 to 

0.071)

5 13.75

(0.36)

7 to 10 0 Begin spray when disease is 

first seen or weather and 

white rust disease pressure 

are expected to initiate a 

disease epidemic. 

Use longer interval for 

preventive or low disease 

pressure.

Hops

Foliar (for 

control of 

Downy mildew 

ease) 6

2.1 to 2.75 

(0.054 to 0.0

(0.071)

6 16.5

(0.426)

7 to 10 3 Begin spray when disease is 

first seen or weather and 

downy mildew disease 

pressure are expected to 

initiate a disease epidemic. 

Use longer interval for 

preventive or low disease 

pressure.

Use water spray of at least 

100 gal/A.

Resistance management: Do not apply more than six (1 soil + 5 foliar) applications of RANMAN 400SC per crop. 

Alternate foliar sprays of RANMAN 400SC with a fungicide with a different mode of action. DO NOT make more 

than three consecutive applications of RANMAN®400SC followed by at least three applications of fungicides 

having different modes of action before applying additional RANMAN®400SC.

2

Soil Incorporation: Alternatively, if desired and for soil with low infiltration rates, apply 20 fl oz per acre in a 

minimum bandwidth of 9 inches along the planting row and incorporate to a soil depth of 6 to 8 inches with a 

precision incorporator in the same operation. Apply in a water volume of at least 50 gal per acre. Transplant the 

seedlings into the treated band. If planting into a bed, a broadcast application can be made prior to forming the bed.

3 Use of an organosilicone and a nonionic surfactant is recommended when disease infection is severe at water

volumes up to 60 gal/A.

4 Restrictions: Do not apply more than 39.5 fl oz per acre per crop growing season [1 soil application at 25.75 fl 

oz/A and 5 foliar applications at 2.75 fl oz/A/application (13.75 fl oz/A)].

5 Resistance management: Do not apply more than five applications of RANMAN®

400SC per crop. Alternate 

foliar sprays of RANMAN®400SC with a fungicide with a different mode of action. DO NOT make more than 

three consecutive applications of RANMAN®400SC followed by at least three applications of fungicides having 

different modes of action before applying additional RANMAN 400SC.

6 Resistance management: Do not apply more than six applications of RANMAN®

400SC per crop. Alternate 

foliar sprays of RANMAN®400SC with a fungicide with a different mode of action. DO NOT make more than 

three consecutive applications of RANMAN®400SC followed by at least three applications of fungicides having 

different modes of action before applying additional RANMAN®400SC.
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Conclusions. The submitted use directions are sufficient to allow evaluation of the submitted 

residue data relative to the proposed uses. The use direction is according to the proposed 

supplemental label. HED notes that soil incorporation of Ranman®400 SC at the rate of 20 fl oz 

per acre before transplant is included in the supplemental label as an alternative to the post

transplant soil drench application. No data have been submitted to support the soil incorporation 

method. However, HED notes that incorporation of Ranman 400SC into the soil (before 

transplant) is already on the current label and has been used on crop field studies from earlier 

petitions (PP#8E7427). No further data are required. 

860.1300 Nature of the Residue Plants

Residue Chemistry Memo DP# 323339, 2/8/07, A. Acierto (PP#1F06305)

Residue Chemistry Memo DP# 285680, 2/20/04, A. Acierto (PP#1F06305)

No plant metabolism studies were submitted with this petition. The qualitative nature of the 

residues in plants is adequately understood for the purposes of this petition based on metabolism 

studies conducted on grape, potato, and tomato, as well as a confined rotational crop in which the 

cyazofamid test substances were radiolabeled in either the phenyl ring ([benzene14C]cyazofamid) or in the fourth position of the imidazole ring ([imidazole14C]cyazofamid). 

The plant and livestock metabolism studies indicate that several of the metabolites resulting from 

the cyazofamid metabolism are common to both plants and livestock. The results of the 

metabolism studies in plants indicated that the parent and CCIM are the major residues (>10% 

TRR). There are no specific toxicity concerns for all other minor metabolites. The confined 

rotational crop study conducted at the 0.64X rate indicated that levels for all metabolites of 

concern are very low (<0.010 ppm) after a 30-day plant-back interval. HED previously

concluded that for risk assessment and tolerance expression, cyazofamid and its CCIM 

metabolite are the residues of concern in plants. 

860.1300 Nature of the Residue – Livestock

Residue Chemistry Memo DP# 323339, 2/8/07, A. Acierto (PP#1F06305)

No livestock metabolism studies were submitted with this petition. The qualitative nature of the 

residues in livestock is adequately understood for the purposes of this petition based on 

metabolism studies conducted in goat and hen in which the cyazofamid test substances were 

radiolabeled in either the phenyl ring ([benzene14C]cyazofamid) or in the fourth position of the 

imidazole ring ([imidazole14C]cyazofamid). These studies have been reviewed and deemed 

acceptable pending submission of additional information pertaining to sample storage intervals. 

The livestock metabolism studies indicate that several of the metabolites resulting from the 

cyazofamid metabolism are common to both plants and livestock. HED concluded that for risk 

assessment and tolerance expression, the parent, cyazofamid and CCIM metabolite are the 

residues of concern in livestock. 

860.1340 Residue Analytical Methods

Enforcement Method: Adequate enforcement methodology is available to enforce the proposed 

tolerances. Cyazofamid and metabolite CCIM are completely recovered (>80% recovery) using 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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FDA’s Multiresidue Protocol D (without cleanup). In addition, an acceptable HPLC/UV method 

is available for use as a single analyte confirmatory method.

Quantification of the residues of cyazofamid and CCIM in the current crop field trials was

achieved by liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) 

as described in “Independent Laboratory Validation of the Residue Method for IKF-916 and 

CCIM in Tomatoes”, Document Number 013033-0, Pyxant Labs Inc. The calculated LOQ and 

LOD were 0.03 ppm and 0.01 ppm, respectively, for cyazofamid and 0.02 ppm and 0.006 ppm, 

respectively, for CCIM. The lowest level of method validation (LLMV) was 0.05 ppm for both 

cyazofamid and CCIM. The method was validated at 0.01, 0.1 and 10 ppm for cyazofamid and 

CCIM prior to and concurrently with study samples. 

The extraction method used for broccoli, cabbage, mustard greens and spinach is described 

briefly as follows: Five gram samples are extracted twice with 50 ml of acetonitrile (ACN) using 

an Ultra-Turrax homogenizer. The combined extracts are filtered through Whatman filter paper.

About 50 ml of ACN and 5 ml water are added to the filter cake, homogenized and again filtered.

The sample extract is rinsed with 5 ml ACN. Rinsate is added to the filter cake and partitioned 

with 100 ml hexane. The acetonitrile phase is collected and concentrated to 1-2 ml (except for 

cabbage which is concentrated to 10 ml) using a rotary evaporator in a water bath at about 45oC.

The residues are dissolved in 20% ACN:water, passed through a Nexus solid phase extraction 

column (SPE) and eluted with 60% ACN:water. Cyazofamid and CCIM residues are quantified 

by LC/MS/MS. 

For hop cones, 1.0 g sample is extracted twice with 50 ml ACN and the combined extracts are 

partitioned with hexane. The ACN extract is collected, diluted to a fixed volume with ACN,

divided into two fractions and cleaned up separately for the residues of cyazofamid and CCIM. 

For cyazofamid, the fraction is concentrated to dryness, dissolved in 5 ml of 50:50 ethyl 

acetate:hexane, sonicated for 15 -30 seconds and passed through a NH2 Solid Phase Extraction 

(SPE) column. Cyazofamid residues are eluted from the column which is then rinsed twice with 

5 ml of 50:50 ethyl acetate:hexane. The cleaned up extract is evaporated to dryness, diluted 

to12.5 ml with 50:50 ACN:water and analysed by LC/MS/MS. For CCIM, the fraction is

evaporated to 2 ml. A 10 ml volume of 30% ACN:water is added, sonicated for 15-30 seconds 

and passed through a Stratea-X Polymer SPE column for clean-up. The column is rinsed with 

30% ACN:water. All eluant were discarded. CCIM was eluted with 60% ACN:water into a 

centrifuge tube and diluted to 12.5 ml with 50:50 ACN:water for analysis by LC/MS/MS. 

The calculations for LOQs and LODs for each crop were provided.

860.1360 Multiresidue Methods

Residue Chemistry Memo DP# 285680, 2/20/04, A. Acierto (PP#1F06305)

Adequate multiresidue method data for cyazofamid and its metabolites were submitted 

previously in conjunction with PP#1F06305. 

The Agency previously concluded that the FDA Multiresidue Method, Protocol D (without 

cleanup) meets the requirement of the Residue Chemistry Test Guideline 860.1360 to enforce 

tolerances for non-fatty commodities and recommended its use as the enforcement method for 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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residues of cyazofamid and CCIM in grape, tomato, the cucurbit vegetable group, and potato

(Memo dated 10/22/03, E. Kolbe, ACB, BEAD). 

860.1380 Storage Stability

Storage stability data submitted previously demonstrated that cyazofamid and its metabolite 

CCIM were reasonably stable for up to ~36 months in tomatoes and up to ~21 months in leaf 

lettuce (DP# 285680, 2/20/04, A. Acierto).

A current freezer storage stability study was conducted using two sets of untreated control crop 

field samples which were fortified separately with cyazofamid and CCIM and stored at <-20oC.

Broccoli, cabbage, mustard greens and spinach samples were fortified at 1.0 ppm and stored for 

788 and 802 days. The hop cone samples were fortified with 0.10 ppm cyazofamid and CCIM 

and stored for 509 days. 

Residues of cyazofamid and CCIM were quantified after the storage duration using the 

LC/MS/MS method. HED notes that 0-day data were not provided with this study. 

The storage conditions and durations of samples from the crop field studies are presented in 

Table 4.

TABLE 4. Summary of Storage Conditions and Durations of Samples from the Crop Field Trials.

Matrix (RAC) Analytes

Storage Temp. 

(

oC)

Actual Storage 

Duration

(Days)

Interval of Demonstrated 

Storage Stability

(Days)

Storage Stability 

Recoveries

(%)

Broccoli

Cyazofamid

<-20 773 788 146, 34, 73

802 172, 66, 91

CCIM

788 140, 55, 86

802 158, 80, 106

Cabbage

Cyazofamid <-20 860 860 108, 114, 115

CCIM 99, 100, 100

Mustard Green 

(Leaves)

Cyazofamid,

<-20 962 977

112, 112, 112

CCIM 101, 109, 113

Spinach 

(Leaves)

Cyazofamid,

<−20 927 949

103, 100, 104

CCIM 113, 118, 123

Hop Cones

Cyazofamid,

<-20 531-552 509

85, 79, 92

CCIM 76, 79, 79

Conclusion. The submitted storage stability data indicate that residues of cyzofamid are stable in 

cabbage, mustard greens, spinach and hop cones. Although the broccoli data were erratic, there 

are sufficient data from the representative crop group 5 to support the stability data for broccoli. 

No additional storage stability study is required. However, the petitioner is reminded that zeroday data should be submitted in future petitions as required in Guideline 860.1300. 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

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

860.1500 Crop Field Trials

Broccoli

DER References: 47870701.der.doc

Six field trials were conducted in the United States encompassing Region 6: TX (1 trial), Region 

10: CA (4 trials), and Region 12: OR (1 trial) during the 2006 growing season. At each test 

location, experimental plants were treated with one post transplant drench application of Ranman 

400SC at the rate of 0.118 lb ai/1000 plants to the base of the plants, followed by five foliar 

applications except CA40 and OR27, which received six foliar applications. All foliar 

applications targeted the rate of 0.072 lb ai/A, at 7(±1) day intervals and 0-day pre-harvest 

interval (PHI). A non-ionic organosilicone surfactant (Silwet L-77) was used in a 4:3 ratio. 

Foliar broadcast applications were made at all field sites except site TX*13, where foliar directed 

applications were made. A minimum of about 2 pounds of broccoli flower heads including 

florets, stem (stalk) and jacket leaves were collected from a minimum of 12 plants from the 

treated and untreated control plots. Treated samples were frozen within 25 minutes of sampling 

and kept frozen until prepared for analysis.

Cabbage

DER References: 47870702.der.doc 

Nine trials were conducted in the United States encompassing Region 1: NY (1 trial), Region 2: 

NJ (3 trials), Region 3: FL (1 trial), Region 5: WI (1 trial), Region 6: TX (1 trial), Region 8: CO 

(1 trial), and Region 10: CA (1 trial) during the 2006 growing season. At each test location, 

experimental plants were treated with one post transplant drench application of Ranman 400SC 

at the rate of 0.118 lb a.i./1000 plants to the base of the plants, followed by five foliar 

applications except NY07, which received six foliar applications. All foliar applications targeted 

the rate of 0.072 lb ai/A, at 7 (±1) day intervals and 0-day pre-harvest interval (PHI) using a nonionic organosilicone surfactant (Silwet L-77) in a 4:3 ratio. Foliar broadcast applications were 

made at all field sites except sites MD21, FL17, and TX*14, where foliar directed applications 

were made. Twelve heads were collected from each plot, cut into halves or quarters and frozen 

within 40 min of sampling. Wrapper leaves were also retained. All samples were kept frozen 

until prepared for analysis.
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 12 of 29

Mustard Greens

DER References: 47870703.der.doc

Nine trials were conducted in the United States encompassing Region 2: MD (1 trial), NJ (1 

trial), GA (1 trial); Region 3: FL (1 trial); Region 4: TN (1 trial); Region 5: WI (1 trial); Region 

6: TX (1 trial); and Region 10: CA (2 trials) during the 2006 growing season. One decline trial 

(TX*15) was conducted with sampling at 0, 1, 3, 6, and 7 days after the last application. 

At each test location, experimental plants were treated with one post transplant drench 

application of Ranman 400SC at the rate of 0.118 lb ai/1000 plants to the base of the plants, 

followed by five foliar applications at a target rate of 0.072 lb ai/A, at 7(±1) day intervals and 0-

day pre-harvest interval (PHI) except for the decline studies which were harvested after 0, 1, 3, 6 

and 7 days. A non-ionic organosilicone surfactant (Silwet L-77) was used in a 4:3 ratio. Foliar 

broadcast applications were made at all field sites except sites MD06, TX*15, and CA44, where 

foliar directed applications were made. Two treated and two untreated control samples were 

collected from each field trial. Four pounds of above ground leaves were collected per sample. 

The treated samples were frozen within 35 minutes, shipped frozen and kept frozen until 

prepared for extraction and analysis.

Spinach 

DER References: 47870704.der.doc

Ten field trials were conducted in the United States encompassing Region 1: NY (1 trial); Region 

2: NJ (1 trial), SC (1 trial), TN (1 trial); Region 4: TN (1 trial); Region 6: TX (2 trials); Region 9: 

CO (1 trial) and Region 10: CA (2 trials) during the 2006 growing season. The number and 

geographic distribution of the supervised crop field trials on spinach are adequate. At each test 

location, experimental plants were treated with five foliar applications of Ranman 400SC at the 

target rate of 0.072 lb a.i./A, at 7 (± 1) day intervals and 0-day pre-harvest interval (PHI). An 

organosilicone surfactant “Silwet L-77” was used in a 4:3 ratio. Foliar broadcast applications 

were made at all field sites except TX*12, where foliar directed applications were made. One 

decline trial was conducted with sampling at 0, 1, 3, 6, and 7 days after the last application. Two 

samples each of treated and untreated samples were collected from each trial. A minimum of 2 

pounds of above ground leaves were collected from a minimum of 12 plants per treatment and 

frozen within 25 minutes. Samples were kept frozen from sampling until prepared for extraction 

and analysis.

Hops

DER References: 47870705.der.doc

Three field trials were conducted in the United States encompassing Region 11: ID (1 trial), WA 

(1 trial); and Region 12: OR (1 trial) during the 2006 growing season. The number and 

geographic distribution of the supervised crop field trials on hops are adequate. At each test 

location, experimental plants were treated with six foliar directed applications of Ranman 400SC 

at a target rate of 0.071 lb ai/A, at 7 (± 1) day intervals and 2-4 days pre-harvest interval (PHI). 

No adjuvants were used in any of the hop field trials. Hop cones were harvested 2-4 days after 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 13 of 29

the last application using techniques simulating commercial practices. The cones were dried 

before sampling, then kept frozen until extracted for analysis.

All raw agricultural commodities were analyzed for residues of cyazofamid and CCIM using the 

LC/MS/MS method which was validated prior to and concurrently with field samples. The 

results of the crop field trials show that after one post transplant drench application and five to 

six foliar applications totaling 0.467–0.552 lb ai/A at 7 (± 1) day intervals and 0-day PHI, the 

maximum total residue (cyazofamid + CCIM) detected was 0.915 ppm in broccoli flower heads, 

0.895 ppm in cabbage heads with wrapper leaves, and 7.0 ppm in mustard greens. In spinach,

after five foliar applications totaling 0.347- 0.366 lb ai/A applied at 7 (± 1) day intervals and 0-

day PHI, the maximum total residues (cyazofamid and CCIM) detected in the leaves were 6.62 

ppm. In hop cones, following six foliar applications totaling 0.425-0.443 lb ai/A at 7 (± 1) days 

intervals and 2-4 days PHI, the maximum combined residues of cyazofamid and CCIM were 7.35 

ppm. Residues detected in all the control samples were <0.01 ppm for both cyazofamid and 

CCIM.

Residue decline data show that cyazofamid and CCIM residues in spinach and mustard greens 

decreased with increasing pre-harvest intervals. Results of the crop field trials are summarized in 

Table 5 and Table 6.

There are sufficient data from the representative crop group 5 to support the storage stability data 

for broccoli. No additional storage stability study is required. However, the petitioner is 

reminded that zero-day data should be submitted in future petitions as required in Guideline 

860.1300. 

TABLE 5. Residue Data from Crop Field Trials with Cyazofamid (Ranman 400 SC)

Trial ID/(City, State)/Year

EPA 

Growing 

Region

Crop/ 

Variety

Commodity 

or Matrix

Total Rate,

(lbs a.i./A)

PHI 

(days)

Cyazofamid

(ppm)

CCIM

(ppm)

Combined 

Residues1

Broccoli1

CA*38/Salinas, CA/2006 10 Broccoli/ 

Everest

Flower 

Head 0.485 0 0.91, 0.76 <0.01, <0.01 0.915, 0.765

CA*39 Salinas, CA/2006 10 Broccoli/ 

Marathon

Flower 

Head 0.482 0 0.41, 0.33 <0.01, <0.01 0.415, 0.335

CA40/Hotville, CA/2006 10 Broccoli/ 

Heritage

Flower 

Head 0.552 0 0.26, 0.19 <0.01, <0.01 0.265, 0.195

CA41/Hotville, CA/2006 10 Broccoli/ 

Triathalon

Flower 

Head 0.479 0 0.28, 0.39 <0.01, <0.01 0.285, 0.395

OR27/Aurora, OR/2006 12 Broccoli/ 

General

Flower 

Head 0.552 0 0.47, 0.45 <0.01, <0.01 0.475, 0.455

TX*13/Weslaco, TX/2006 6

Broccoli/ 

Gypsy

Flower 

Head 0.486 0 0.18, 0.27 <0.01, <0.01 0.185, 0.275

Cabbage2

CA*42/ Salinas, CA/ 2006

10 Cabbage/ 

Charmant

Head with 

Wrapper 

Leaves

0.482 0 0.25, 0.25 <0.01, <0.01 0.255, 

0.255

CO05/Brighton, CO/ 2006

8

Cabbage/ 

Rocket

Head with 

Wrapper 

Leaves

0.483 0 0.30, 0.29 <0.01, <0.01 0.305, 

0.295
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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FL17/ Citra, FL/2006 3 Cabbage/ 

Bravo

Head with 

Wrapper 

Leaves

0.496 0

0.61, 0.50

0.016, 0.012 0.626, 

0.512

MD21/Salisbury, MD/ 2006 2 Cabbage/ 

Primax

Head with 

Wrapper 

Leaves

0.478 0

0.87, 0.63

0.025, 0.020 0.895, 

0.650

NJ08/Bridgeton, NJ/ 2006 2 Cabbage/ 

Wisconsin 

Golden Acre

Head with 

Wrapper 

Leaves

0.467 0 0.40, 0.16 0.013, <0.01 0.413, 

0.165

NY07/Freeville, NY/ 2006 1 Cabbage/ 

Bobcat 

(Hybrid 

Cabbage)

Head with 

Wrapper 

Leaves

0.531 0 0.22, 0.17 <0.01, <0.01 0.225, 

0.175

SC*05/Charlston, SC/ 2006 2 Cabbage/ 

Copenhagen

Head with 

Wrapper 

Leaves

0.478 0 0.16, 0.14 <0.01, <0.01 0.165, 

0.145

TX*14/Weslaco, TX/ 2006 6 Cabbage/ 

Blue Vantage

Head with 

Wrapper 

Leaves

0.482 0 0.33, 0.31 <0.01, <0.01 0.335, 

0.315

WI10/Arlington, WI/2006 5 Cabbage/ 

Blue Vantage

Head with 

Wrapper 

Leaves

0.476 0 0.12, 0.13 <0.01, <0.01 0.125, 

0.135

Mustard Greens3

CA*43/ Salinas, CA/2006

10

Greens 

(Mustard)/ 

Green Wave

Mustard 

Greens

(leaves)

0.482 0 2.9, 3.9 0.030, 0.040 2.93, 3.94

CA44/ Riverside, CA/ 2006 10

Greens 

(Mustard)/ 

Florida 

Broadleaf

Mustard 

Greens

(leaves)

0.483 0 3.0, 3.6 0.032, 0.032 3.03, 3.63

FL18/Citra, FL /2006 3

Greens 

(Mustard)/ 

Florida 

Broadleaf

Mustard 

Greens

(leaves)

0.503 0 6.0, 5.9 0.094, 0.090 6.09, 5.99

GA*06/Tifton, GA/2006 2

Greens 

(Mustard)/ 

Green Wave

Mustard 

Greens

(leaves)

0.491 0 6.8, 5.8 0.056, 0.050 6.86, 5.85

MD06/ Salisbury, MD/ 2006 2

Greens 

(Mustard)/ 

Green Wave

Mustard 

Greens

(leaves)

0.483 0 5.5, 5.5 0.050, 0.050 5.55, 5.55

NJ09/ Bridgeton, NJ/ 2006 2

Greens 

(Mustard)/ 

Southern 

Curled

Mustard 

Greens

(leaves)

0.472 0 3.0, 4.0 0.13, 0.17 3.13, 4.17

TN06/Jackson, TN/2006 4

Grenns 

(Mustard)/ 

Florida 

Broadleaf

Mustard 

Greens

(leaves)

0.494 0 1.5, 1.3 0.11, 0.10 1.61, 1.40

TX*15/ Weslaco, TX / 2006 6

Greens 

(Mustard)/ 

Florida 

Broadleaf

Mustard 

Greens

(leaves)

0.477

0 2.1, 1.7 0.038, 0.032 2.138, 

1.732

1 1.2, 1.4 0.019, 0.019 1.219, 

1.419

3 0.33, 0.38 <0.01, <0.01 0.335, 

0.385

6

0.061, 

0.066 <0.01, <0.01 0.066, 0.071

7

0.022, 

0.024 <0.01, <0.01 0.027, 0.029
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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WI11 / Arlington, WI 5

Mustard 

Greens / 

Florida 

Broadleaf

Mustard 

Greens

(leaves)

0.474 0 3.8, 3.6 0.19, 0.17 3.990, 3.77

Spinach/ 4

CA* 36/ Salinas, CA/ 2006 10 Spinach/ 

Whale F106

Greens

(leaves) 0.364 0 3.9, 3.3 0.044, 0.045 3.944,3.345

CA*37/Salinas, CA/2006 10 Spinach/ 

Space F1

Greens

(leaves) 0.360 0 3.0, 3.6 0.036, 0.043 3.036, 3.643

CO04/Fort Collins, CO/ 2006 9

Spinach/ 

Bloomsdale 

Savoy

Greens

(leaves) 0.365

0 2.4, 1.9 0.036, 0.032 2.436, 

1.932

1 2.5, 1.6 0.031, 0.023 2.531, 

1.623

3 1.2, 1.2 0.015, 0.012 1.215, 

1.212

4 0.9, 1.0 0.013, 0.016 0.913, 

1.016

6 0.69, 0.82 <0.01, 0.011 0.695, 

0.831

NJ07/ Bridgeton, NJ/ 2006 2

Spinach/ 

Melody

Greens

(leaves) 0.347 0 6.3, 6.5 0.12, 0.12 6.42, 6.62

NY06/ Freeville, NY/ 2006 1

Spinach/ Tyee 

F1

Greens

(leaves) 0.361 0 2.1, 1.9 0.031, 0.027 2.131, 1.927

SC*04/ Charleston, SC /2006 2

Spinach/ 

Skookum 

Hybrid

Greens

(leaves) 0.361 0 2.6, 3.1 0.081, 0.094 2.681, 3.194

TN07/ Crossville, TN/ 2006 2

Spinach/ 

Bloomsdale

Greens

(leaves) 0.366 0 3.6, 3.2 0.10, 0.086 3.70, 3.286

TN08/Jackson, TN / 2006 4

Spinach/ 

Bloomsdale

Greens

(leaves) 0.365 0

1.8, 2.2 0.088, 0.11 1.888, 2.31

TX*11/ Weslaco, TX/ 2006 6

Spinach/ 

Samish

Greens

(leaves) 0.359 0 1.7, 1.4 0.064, 0.054 1.764, 1.454

TX*12/ Weslaco, TX/ 2006 6

Spinach/ 

Spargo F1

Greens

(leaves) 0.359 0 4.1, 5.1 0.13, 0.15 4.23, 5.25

Hops

09823.07-ID01 /Parma, ID/ 

2007 11 Hops/ Nagget Mature hop 

cones

0.425 4 5.7, 6.9 0.13, 0.13 5.83, 7.03

09823.07-OR04 /Aurora, 

OR/ 2007 12 Hops/ Nagget Mature hop 

cones

0.440 2 2.8, 3.6 0.21, 0.28 3.01, 3.88

09823.07-WA02/B-49 

Field/2007 11 Hops/ Nagget Mature hop 

cones

0.443 3 2.5, 2.5 0.42, 0.45 2.92, 2.95

1

For Residue values <LOQ (0.01 ppm), 1⁄2 LOQ (0.005 ppm) was used to calculate combined residues

3

For residue values <LOQ (0.01 ppm), 1⁄2 LOQ (0.005 ppm) was used for CCIM residues

4

0.005 ppm was used for CCIM residues (< 0.01 ppm) to calculate combined residues
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 16 of 29

TABLE 6. Summary of Residue Data from Crop Field Trials with Cyazofamid

Commodity Analyte Total Application 

Rate

(lbs a.i./A)

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 Median2

(STMdR)

Mean2

(STMR)

Standard

Deviation2

Broccoli

Broccoli 

Flower Head

Cyazofamid 0.479–0.552 0 12 0.18 0.91 0.84 0.36 0.41 0.22

CCIM NA3

0 12 < 0.01 < 0.01 0.005 0.005 0.005 0

Cabbage

Cabbage 

Head with 

Wrapper 

Leaves

Cyazofamid

0.467–0.531 0 18 0.12 0.87 0.75 0.27 0.32 0.21

CCIM NA3

0 18 < 0.01 0.025 0.02 0.01 0.01 0.01

Mustard Greens

Mustard 

Greens

(leaves)

Cyazofamid 0.472 – 0.503 0 18 1.3 6.8 6.3 3.7 3.9 1.7

Mustard 

Greens

(leaves)

Cyazofamid 0.477 1 2 1.2 1.4 1.3 1.3 1.3 0.14

Mustard 

Greens

(leaves)

Cyazofamid 0.477 3 2 0.33 0.38 0.36 0.36 0.36 0.035

Mustard 

Greens

(leaves)

Cyazofamid 0.477 6 2 0.061 0.066 0.064 0.064 0.064 0.0035

Mustard 

Greens

(leaves)

Cyazofamid 0.477 7 2 0.022 0.024 0.023 0.023 0.023 0.0014

Mustard 

Greens

(leaves)

CCIM NA40 18 0.030 0.19 0.18 0.053 0.081 0.053

Mustard 

Greens

CCIM NA 1 2 0.019 0.019 0.019 0.019 0.019 0

(leaves) CCIM NA 3 2 <0.01 0.012 0.009 0.009 0.009 0.005

Mustard 

Greens

CCIM NA 6 2<0.01 <0.01 0.005 0.005 0.005 0

(leaves) CCIM NA 7 2<0.01 <0.01 0.005 0.005 0.005 0

Spinach Leaves

Spinach 

Leaves Cyazofamid 0.347 - 0.366 0 20 1.4 6.5 6.4 3.1 3.2 1.4

Spinach 

Leaves Cyazofamid 0.365 1 2 1.6 2.5 2.1 2.1 2.1 0.64

Spinach 

Leaves Cyazofamid 0.365 3 2 1.2 1.2 1.2 1.2 1.2 0

Spinach 

Leaves Cyazofamid 0.365 4 2 0.90 1.0 0.95 0.95 0.95 0.071

Spinach 

Leaves Cyazofamid 0.365 6 2 0.69 0.82 0.76 0.76 0.76 0.092

Spinach 

Leaves CCIM NA3

0 20 0.027 0.15 0.14 0.073 0.075 0.038

Spinach 

Leaves CCIM NA 1 2 0.023 0.031 0.027 0.027 0.027 0.01

Spinach 

Leaves CCIM NA 3 2 0.012 0.015 0.0135 0.0135 0.0135 0.0021
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 17 of 29

Spinach 

Leaves CCIM NA 4 2 0.013 0.016 0.0145 0.0145 0.0145 0.0021

Hops

Hop Cones Cyazofamid 0.425-0.443 2-4 6 2.5 6.9 6.3 3.2 4.0 1.9

CCIM NA22 - 4 6 0.13 0.45 0.435 0.245 0.27 0.14

1

Highest Average Field Trial

2

For residue values <LOQ, half of the LOQ (0.005 ppm) was used to calculate the median, mean, HAFT, and standard deviation

3Not Applicable 

Conclusion. The submitted crop field studies are adequate to support the proposed minor uses. 

The studies were conducted consistent with standard agricultural practices as per proposed use 

pattern. The number and geographic distribution of the supervised crop field trials are adequate.

Weather conditions at the field sites were generally considered normal; anomalous weather 

conditions were reported at some field sites, which did not have any adverse impact on the 

studies. 

Residue decline data show that cyazofamid and CCIM residues in mustard greens and spinach 

decreased with increasing pre-harvest intervals.

Adequate storage stability data are available.

860.1550 Proposed Tolerances

HED has concluded previously that the parent and the metabolite CCIM are the residues of 

concern for risk assessment and tolerance expression in plants. Tolerances are currently

established in 40 CFR §180.601(a) for the combined residues of cyazofamid and CCIM 

expressed as cyazofamid in/on carrot, roots at 0.09 ppm, okra at 0.40 ppm, potato at 0.02 ppm, 

vegetable, cucurbit, group 9 at 0.10 ppm, and vegetable, fruiting, group 8 at 0.40 ppm. In 

addition, tolerances with regional registrations are established in 40 CFR §180.601(c) in/on grape 

at 1.5 ppm. HED recommends modification of the tolerance expressions for cyazofamid 

according to the new compliance/measurement policy (Interim Guidance on Tolerance 

Expressions, Steve Knizner, May 27, 2009) to read as follows:

“HED recommends that the tolerance definition entry in 40 CFR 180.601 be revised as 

follows: (a) General. Tolerances are established for residues of the fungicide cyazofamid, 

including its metabolites and dehgradates, in or on the commodities in the table below. 

Compliance with the tolerance levels specified below is to be determined by measuring only 

the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide 

and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the 

stoichiometric equivalent of cyazofamid, in or on the commodity.”

The Agency’s SOP “Guidelines for Setting Pesticide Tolerances Based on Field Trial Data” was 

utilized for determining the appropriate tolerance level for each commodity (Appendix II). 

As the minimum and maximum recommended tolerances differ by less than 5x, a crop group 

tolerance is appropriate for the Brassica Head and Stem, Crop Subgroup 5A. Although cabbage 

belongs to both crop subgroup 5A and 5B, the tolerance of 12.0 ppm is appropriate for Brassica, 

Leafy Greens, Crop Subgroup 5B based on mustard greens, the representative crop. 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 18 of 29

HED has concluded that turnip greens will be moved from the leaves of root and tuber vegetables 

crop group (group 2) to the Brassica leafy vegetables crop group 5, subgroup 5B: (memorandum, 

B. Schneider, 6/14/2002). However, until the regulations have been finalized in the Federal 

Register, a separate tolerance is needed for turnip greens at the same level as the Brassica, Leafy

Greens, Crop Subgroup 5B at 12.0 ppm.

The recommended tolerances for spinach and hops are 9 and 10.0 ppm, respectively. The 

recommended tolerances are listed in Table 7.

Canada has established maximum residue limits (MRL) for residues of cyazofamid in/on several 

commodities, but has not established maximum residue limits for the commodities of this 

petition. No maximum residue limits (MRLs) for residues of cyazofamid have been 

establishedby the Codex Alimentarius Commission. 

Table 7. Tolerance Summary for Cyazofamid.

Commodity Proposed 

Tolerance 

(ppm

Existing 

Tolerance 

(ppm)

Recommended 

Tolerance 

(ppm)

Comments; Correct Commodity 

Definition

40 CFR 180.601 (a)

Brassica, head & stem, 

crop subgroup 5A 1.2 1.2

Brassica, leafy greens, 

crop subgroup 5B

12.0 12.0

Hops 10.0 10.0

Spinach 9.0 9.0

Turnip greens 12.0 12.0 Until the regulations have been 

finalized in the Federal Register to 

move turnip greens from the leaves 

of root and tuber vegetables crop 

group (group 2) to the Brassica leafy 

greens subgroup 5B, a separate 

tolerance is needed at the same level 

as the Brassica, Leafy Greens, 

Subgroup 5B.

1

1Memorandum, B. Schneider, 6/14/2002.

E. REFERENCES

DP Barcode: D285680

Subject: Cyazofamid. Petition for the Establishment of Permanent Tolerances for use on 

Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes. Summary of 

Analytical Chemistry and Residue Data 

From: Amelia Acierto

To: Janet Whitehurst/Cynthia Giles-Parker, PM Team #22

Date: 2/20/2004
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 19 of 29

MRID: 45638502, 45638503, 45638504, 45638505, 45638506-45638510, 45409014-

45409019, 45409020, 45409022, 45409023-45409025, 45409026-45409035, 

45409036 

DP Barcode: 357042

Subject: Amend Section 3 Registration to Add Uses on Fruiting Vegetables, Okra, Grape 

(East of the Rocky Mountains), and Greenhouse Vegetable Transplants. 

Summary of Analytical Chemistry and Residue Data.

From: Amelia Acierto

To: Barbara Madden, RM #5

Date: 3/18/2009

MRID: 47528401, 47528402, 47532601

Attachments: 

Appendix I - International Residue Limit Status sheet

Appendix II - Tolerance Assessment Calculations

Template Version April 2008
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 20 of 29

APPENDIX I

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 4-

Chloro-2-cyano-N,Ndimethyl-5-(4-

methylphenyl)-1Himidazole-1-sulfonamide

Common Name:

Cyazofamid

□ Proposed tolerance

□ Reevaluated tolerance

X Other Recommended

Date: 12/2/08

Codex Status (Maximum Residue Limits) U. S. Tolerances

√ No Codex proposal step 6 or above

□ No Codex proposal step 6 or above for the crops 

requested

Petition Number: PP#9E7615

DP#: 371163

Other Identifier: 

Residue definition (step 8/CXL): N/A Reviewer/Branch: A.Acierto/RAB3

Residue definition: Combined residues of cyazofamid, 

4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1Himidazole-1-sulfonamide and its metabolite, CCIM, 4-

chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, 

expressed as cyazofamid 

Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm)

Brassica, head & stem, crop 

subgroup 5A

1.2

Brassica, leafy greenss, crop 

subgroup 5B

12.0

Turnip greens 12.0

Spinach 9.0

Hops 10.0

Limits for Canada Limits for Mexico

□ No Limits

√ No Limits for the crops requested

√ No Limits

□ No Limits for the crops requested

Residue definition: 4-chloro-2-cyano-N,N-dimethyl-5-

(4-methylphenyl)-1H-imidazole-1-sulfonamide, 

including the metabolite 4-chloro-5-(4-methylphenyl)-

1H-imidazole-2-carbonitrile 

Residue definition: N/A

Mexico adopts Codex MRLs or US tolerances for its 

export purposes.

Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg)

Notes/Special Instructions:

S. Funk, 3/6/2010
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 21 of 29

Appendix II. Tolerance Assessment Calculations.

For each of the crops listed below, the Guidance for Setting Pesticide Tolerances Based on Field 

Trial Data (SOP), along with the tolerance spreadsheet, was used for calculating recommended 

tolerances. As specified in the SOP, the minimum of the 95% upper confidence limit (UCL) on 

the 95th percentile and the point estimate of the 99th percentile was selected as the tolerance value 

in cases when the dataset was large (greater than 15 samples) and reasonably lognormal. For 

datasets that were small (≤15 samples) and reasonably lognormal, the upper bound estimate of 

the 95th percentile based on the median residue value was compared to the minimum of the 95% 

UCL on the 95th percentile and the point estimate of the 99th percentile, and the minimum value 

was selected as the tolerance value. For datasets that were not lognormal, the upper bound on the 

89th percentile was selected as the tolerance value (distribution-free method). The rounding 

procedures specified in the SOP were also used.

Brassica, Crop Subgroup 5A

The dataset used to establish tolerances for residues of Cyazofamid on Brassica Crop Subgroup 

5A consisted of field trial data for the representative crops: broccoli and cabbage and represented 

application rates of 0.485-0.506 lb ai/A (1 soil drench +5-6 foliar applications) with a PHI of 0 

day. As specified by the SOP, the field trial application rates and PHIs are within 25% of the 

maximum label application rate and minimum label PHI, respectively. The residue values used

to calculate the tolerance are provided in Table I. 

All field trial sample results for broccoli and cabbage were above the LOQ (0.01 ppm). The 

dataset for was 12 samples for broccoli, and 18 samples for cabbage. The dataset for each crop 

was entered into the tolerance spreadsheet. Visual inspection of the lognormal probability plots 

for each crop (Figures I-1and I-3) indicates that the datasets for both crops are reasonably

lognormal. The results from the approximate Shapiro-Francia test statistic (Figures I-2 and I-4) 

confirmed that the assumption of lognormality should not be rejected. 

Using the tolerance spreadsheet, the recommended tolerances are 1.2 ppm for broccoli, and 1.1 

ppm for cabbage. Because the minimum and maximum recommended tolerances differ by less

than 5x, a crop group tolerance is appropriate Brassica, Crop Subgroup 5A. The recommended 

value is 1.2 ppm, the maximum of the recommended individual tolerances.

Brassica, Crop Subgroup 5B

The dataset used to assess a tolerance for Cyazofamid residues in/on Brassica Crop Subgroup 5B

consisted of field trial data for the representative crop mustard greens and represented application 

rates of 0.484 lb ai/A (1 soil drench + 5-6 foliar applications) with a PHI of 0 day. As specified 

by the SOP, the field trial application rates and PHIs are within 25% of the maximum label 

application rate and minimum label PHI, respectively. The residue values used to calculate the 

tolerance are included in Table I. 

All field trial sample results for broccoli and cabbage were above the LOQ (0.01 ppm). The 

dataset for mustard greens was 18 samples. The dataset for the crop was entered into the 

tolerance spreadsheet. Visual inspection of the lognormal probability plots for each crop (Figure 

I-5) indicates that the dataset for mustard greens is reasonably lognormal. The results from the 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 22 of 29

approximate Shapiro-Francia test statistic (Figure I-6) confirmed that the assumption of 

lognormality should not be rejected. 

Using the tolerance spreadsheet, the recommended tolerance for mustard greens is 12 ppm. 

Because mustard greens is the representative commodity for Brassica Crop Subgroup 5B, a crop 

group tolerance is appropriate. The recommended value is 12 ppm is recommended for 

individual tolerances.

Spinach 

The dataset used to assess a tolerance for Cyazofamid residues in/on spinach consisted of field 

trial data and represented application rate of 0.361lb ai/A (5 foliar applications) with a PHI of 0 

day. As specified by the SOP, the field trial application rates and PHIs are within 25% of the 

maximum label application rate and minimum label PHI, respectively. The residue values used 

to calculate the tolerance are provided in Table II-1. 

All field trial sample results for spinach were above the LOQ (0.01 ppm). The dataset for 

spinach was 20 samples. The dataset for the crop was entered into the tolerance spreadsheet. 

Visual inspection of the lognormal probability plots for each crop (Figure II-1) indicates that the 

dataset for mustard greens is reasonably lognormal. The results from the approximate ShapiroFrancia test statistic (Figure II-2) confirmed that the assumption of lognormality should not be 

rejected. 

Using the tolerance spreadsheet, the recommended tolerance for spinach is 9 ppm. 

Hops

The dataset used to assess a tolerance for Cyazofamid residues in/on hops consisted of field trial 

data and represented application rates of 0.436 lb ai/A (6 foliar applications) with a PHI of 0 

day. As specified by the SOP, the field trial application rates and PHIs are within 25% of the 

maximum label application rate and minimum label PHI, respectively. The residue values used 

to calculate the tolerance are provided in Table II-1. 

The field trial sample results for hops were above the LOQ (0.01 ppm). The dataset for hop was 

6 samples. The dataset for the crop was entered into the tolerance spreadsheet. Visual inspection 

of the lognormal probability plots for each crop (Figure II-3) indicates that the dataset for hops is 

reasonably lognormal. The results from the approximate Shapiro-Francia test statistic (Figure II4) confirmed that the assumption of lognormality should not be rejected. 

Using the tolerance spreadsheet, the recommended tolerance for hops is 10 ppm. 
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Table I. Residue data used to calculate tolerance for cyazofamid residues on broccoli, cabbage and 

mustard greens.

Brassica Crop Subgroup 5A Brassica Crop Subgroup 5B

Regulator: EPA EPA EPA

Chemical: Cyazofamid Cyazofamid Cyazofamid

Crop: Broccoli Cabbage Mustard Greens

PHI: 0 day 0 day 0 day

App. Rate: (1 Soil 

Drench + 5 Foliar) 0.506 lb ai/A 0.485 lb ai/A 0.484 lb ai/A

Submitter: IR-4 IR-4 IR-4

MRID Citation: MRID 47528401 MRID 47528402 MRID 47528403

Residues Residues Residues

0.915 0.255 2.93, 

0.415 0.255 3.03, 

0.265 0.626 6.09, 

0.285 0.895 6.86, 

0.475 0.413 5.55

0.185 0.225 3.13

0.765 0.165 1.61

0.335 0.335 2.14

0.195 0.125 3.99

0.395 0.305 3.94

0.455 0.295 3.63

0.275 0.512 5.99

0.650 5.85

0.165 5.55

0.175 4.17

0.145 1.40

0.315 1.73

,0.135 3.77
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Figure I-1. Lognormal Probability Plot of Cyazofamid Residues in/on Broccoli Following One Post 

Transplant Drench and Five to Six Foliar Applications of RanMan 400 SC at a Total Rate of 0.506 lb ai/A.

Lognormal Probability Plot

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

1.0000

0.5000

0.2500

0.1250

y = 0.5067x - 0.9989

R

2

 = 0.9609

Percentiles

Concentrations

EPA Cyazofamid Brocolli 0 0.506 lb ai/A IR-4

Figure I-2. Tolerance spreadsheet summary of cyazofamid field trial data for broccoli.

Regulator: EPA

Chemical: Cyazofamid

Crop: Brocolli

PHI: 0

App. Rate: 0.506 lb ai/A

Submitter: IR-4

n: 12

min: 0.19

max: 0.92

median: 0.37

average: 0.41

95th Percentile 99th Percentile 99.9th Percentile

0.80 1.0 1.2

(1.1) (1.3) (--)

0.90 1.2 1.7

(1.5) (2.5) (--)

1.0

1.1

2.5

0.9609

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Figure I-3. Lognormal Probability Plot of Cyazofamid Residues in/on Cabbage Following One Post 

Transplant Drench and Five to Six Foliar Applications of RanMan 400 SC at a Total Rate of 0.485 lb ai/A.

Figure I-4. Tolerance spreadsheet summary of cyazofamid field trial data for cabbage.

Regulator: EPA

Chemical: Cyazofamid

Crop: Cabbage

PHI: 0

App. Rate: 0.485 lb ai/A

Submitter: IR-4

n: 18

min: 0.13

max: 0.90

median: 0.28

average: 0.33

95th Percentile 99th Percentile 99.9th Percentile

0.70 0.90 1.0

(0.90) (1.1) (--)

0.80 1.1 1.7

(1.2) (2.0) (--)

0.90

1.0

1.6

0.9642

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD

Lognormal Probability Plot

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

1.0000

0.5000

0.2500

0.1250

0.0625

y = 0.594x - 1.2669

R

2 = 0.9642

Percentiles

Concentrations

EPA Cyazofamid Cabbage 0 0.485 lb ai/A IR-4
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Figure I-5. Lognormal Probability Plot of Cyazofamid Residues in/on Mustard Greens Following One Post 

Transplant Drench and Five Foliar Applications of RanMan 400 SC at a Total Rate of 0.484 lb ai/A.

Figure I-6. Tolerance spreadsheet summary of cyazofamid field trial data for mustard greens.

Regulator: EPA

Chemical: Cyazofamid

Crop: Mustard Greens

PHI: 0

App. Rate: 0.484 lb ai/A

Submitter: IR-4

n: 18

min: 1.40

max: 6.86

median: 3.86

average: 3.96

95th Percentile 99th Percentile 99.9th Percentile

7.0 8.0 10

(9.0) (10) (--)

8.0 12 17

(12) (19) (--)

12

10

25

0.9374

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD

Lognormal Probability Plot

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

7.0000

3.5000

1.7500

0.8750

y = 0.4915x + 1.2757

R

2 = 0.9374

Percentiles

Concentrations

EPA Cyazofamid Mustard Greens 0 0.484 lb ai/A IR-4
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Table II- Residue data used to calculate tolerance for cyazofamid residues on 

spinach and hops.

Regulator: EPA EPA

Chemical: Cyazofamid Cyazofamid

Crop: Spinach Hops

PHI: 0 day 0 day

App. Rate:

(Foliar) 0.36 lb ai/A 0.436 lb ai/A

Submitter: IR-4 IR-4

MRID Citation: MRID 47528404 MRID 47528405

Residues Residues

3.944 5.83

3.036 3.01

2.436 2.92

6.42 7.03

2.131 3.88

2.681 2.95

3.70 

1.888 

1.764 

4.23 

3.345

3.643

1.932

6.62

1.927

3.194

3.286

2.31

1.454

5.25
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

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Figure II-1. Lognormal Probability Plot of Cyazofamid Residues in/on Spinach Following Five Foliar 

Applications of RanMan 400 SC at a Total Rate of 0.361 lb ai/A.

Figure II-2. Tolerance spreadsheet summary of cyazofamid field trial data for spinach.

Regulator: EPA

Chemical: Cyazofamid

Crop: Spinach

PHI: 0

App. Rate: 0.361 lb ai/A

Submitter: IR-4

n: 20

min: 1.45

max: 6.62

median: 3.12

average: 3.26

95th Percentile 99th Percentile 99.9th Percentile

6.0 7.0 8.0

(7.0) (9.0) (--)

7.0 9.0 12

(9.0) (13) (--)

8.0

8.0

17

0.9750

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD

Lognormal Probability Plot

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

7.0000

3.5000

1.7500

0.8750

y = 0.4379x + 1.0927

R

2 = 0.975

Percentiles

Concentrations

EPA Cyazofamid Spinach 0 0.361 lb ai/A IR-4
Cyazofamid Summary of Analytical Chemistry and Residue Data DP#: 371162

Page 29 of 29

Figure II-3. Lognormal Probability Plot of Cyazofamid Residues in/on Hops Following Six Foliar 

Applications of RanMan 400 SC at a Total Rate of 0.436 lb ai/A.

Figure I-4. Tolerance spreadsheet summary of cyazofamid field trial data for hops.

Lognormal Probability Plot

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

8.0000

4.0000

2.0000

y = 0.3852x + 1.3874

R

2 = 0.8484

Percentiles

Concentrations

EPA Cyazofamid Hops 3 0.436 IR-4

Regulator: EPA

Chemical: Cyazofamid

Crop: Hops

PHI: 3

App. Rate: 0.436

Submitter: IR-4

n: 6

min: 2.92

max: 7.03

median: 3.45

average: 4.27

95th Percentile 99th Percentile 99.9th Percentile

8.0 9.0 10

(11) (14) (--)

8.0 10 14

(17) (30) (--)

13

10

30

0.8484

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD