Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 1 of 29 UNITED STA

TES ENVIRONMENTA L PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDE AND TOXIC SUBSTANCES 

### MEMORANDUM Date: February 24 , 20 1 0 SUBJECT: Cyazofamid . Tolerance Petition for Uses on Brassica ( C ole) Leafy Vegetables Crop Group 5, Turnip Greens, Spinach, and Hops . Summary of Analy tical Chemistry

and Residue Data. PC Code: 085651 DP Barcode: D 37 116 2 Decision No.: 420982 Registration No. : EPA Reg. No s . 71512 - 2 & 71512 - 3 Petition No.: 9E7615 Regulatory Action: Section 3 Registration Risk Assessment Type: NA Case No.: NA T XR 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 Sum ma ry Table MRID No. Study Type Com me nts 47870701 860.1500 Broccoli New DER; 4 7870701 .der.doc 47870702 860.1500 Cabbage New DER; 4787070 2 .der.doc 47870703 860.1500 mustard greens New DER; 4787070 3. der.doc 47870704 860.1500 spinach New DER; 4787070 4 .der.doc 47870705 860.1500 hops New DER; 4787070 5 .der.docCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 2 of 29 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, Oklahom a, New York, California, Georgia, North Carolina, Oregon, Virginia, Tennessee, Ohio, and Washington, has submitted a petition proposing th e establishment of permanent tolerance s for the combined residues of the fungicide cyazofamid [ 4 - chloro - 2 - cyano -N,N - di methyl - 5 - (4 - methylphenyl) - 1 H - imidazole - 1 - sulfonamide ] and its metabolite CCIM [ 4 - chloro - 5 - (4 - methylphenyl) - 1 H
- imidazole - 2 - carbonitrile ] in/ on the following raw agricultural commodities (RACs) : Br assica, 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 ® 

### 4 00SC is the product proposed for minor use s on B rassica crop subgroup 5A and 5B as a single post transplant soil drench appli ed 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 spinac h or hops. T he formulated produ ct 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 (RTI s ) 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 . P reharvest intervals (PHI s) are proposed at 0 day for the B rassica vegetable s 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 . T olerances 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. 4 0 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 , go at 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 Che mistry and Residue Data DP#: 37116 2



### Page 3 of 29 However, based on available ruminant metabolism studies in goats, HED required that for future cattle feeding s tudie s, cyazofamid, CCIM, CCBA [ 4 - (4 - chloro - 2 - cyanoimidazole - 5 - yl )be nzoic a cid] and CCBA - cysteine conjugates should be analy ze d (PP# 1F6305, D285680, Amelia M. Acierto, 2/20/2004). An acceptable analy

tical 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. Inaddition, an acceptable high performance liquid chromatography

/ultraviolet det e ctor ( HPL C/UV ) method is available for use as a single analy te confirmatory

method . An a dequate data collection method derived from “Independent Laboratory Validation of the Residue Method for IKF - 916 and CCIM in T omatoes ” , Document Number 013033 - 0, Py xant Lab s Inc, is available. Quantification of the re sidues of cyazofamid and CCIM is achieved by liquid chromatography with tandem mass spectrometric detection (L C/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 (LLM V) was 0.05 ppm for both cyazofamid and CCIM. The crop field trial data submitted are adequate t o support the proposed new minor use s of cyazofamid in/on B rassica 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 c abbage 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 . Res idue 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 to support the storage durations and conditions of samples of cabbage, mu stard greens, spinach and hops. Although the concurrent recoveries were acceptable for broc c oli, the storage stability data were erratic, which, according to the petitioner may have been due to the spiking solution that appeared to have degraded ( separate d) 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 tole rance spreadsheet calculations indicate that the proposed tolerances for the combined residues of cyazofamid and CCIM are appropriate. Canada has established maximum residue limit s (MRL) for residues of c yazofamid in/on several commodities, but has not es tablished maximum residue limits for the commodities of this petition. No maximum residue limi t s (MRL s) for residues of c yazofamid have been established

by the Codex Alimentarius Commission .Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 4 of 29 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 preclud e 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 f or residues of the fungicide cyazofamid, including its metabolite s 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

- dime thyl - 5 - (4 - methylphenyl) - 1 H - imidazole - 1 - sulfonamide and its metabolite, 4 - chloro - 5 - (4 - methylphenyl) - 1 H
- 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 express ions 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 asse ssment is forthcoming. Background Cyazofamid is a broad - spectrum fungicide active against oomycete fungi (such as Ph y tophthora , Plasmopara , Pseudoperonospora , and Pythium ) and Plasmodiophoromycetes ( Plasmodiospora brassicae ). It inhibits all stages of fungal development in the life cycle of Phy tophthora infestans which causes late blight disease i n potatoes and tomatoes, and inhibits the germination and formation of zoosporangia, germination of cy tospores, zoospore mobility , and mycelial growth. It controls downy mildew i n 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 roo t (

Pasmodiophora brassiceae ) and downy mildew ( Peronospora parasitica ) in B rassica vegetables, white rust (

Albugo occidentalis ) disease in spinach; and downy mildew ( Pseudoperonospora humuli ) in hops . The chemical structure, nomenclature and physicochem ical properties of the technical grade of cyazofamid and its metabolite CCIM, are shown in Table s 1 and 2.Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 5 of 29 Table 1. Test Compound Nom enclature. Compound Chemical Structure

N N C H3 Cl CN S O 2 N ( C H3 ) 2 Common name Cyazofamid Company experimental name N/A IUPAC name 4 - chloro - 2 - c yano -N, N - dimethyl - 5 -

p - tolylimidazole - 1 - sulfonamide CAS name 4 - chloro - 2 - cyano -N,N - dimethyl - 5 - (4 - methylphenyl) - 1 H - imidazole - 1 - sulfonamide CAS registry number 120116 - 88 - 3 End - use product (EP) Ranman® 400SC Agricultural Fungicide (EPA Reg. No. 71512 - 3) Co mp ound Chemical Structure of metabolite

N H N C H3 Cl CN Common name CCIM IUPAC name 4 - chloro - 5 - p - tolylimidazole - 2 - carbonitrile CAS name 4 - chloro - 5 - (4 - methylphenyl) - 1 H
- 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, 13 th Edition Density at 20 °C (g/mL) 1.446Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 6 of 29 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 - 5 Pa Dissociation constant (pKa) Does not dissociate in water. No pKa in the pH range of 2 - 12. Octanol/water partition coefficient LogKOW = 3.2 KOW = 1.585 x 10 3 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 . T he 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. Seasona l

Applic. Rate fl oz (lb ai/A) TRI

(days) PHI

(days) Use Directions and

Limitations C rop G roup 5, B rassica (Cole) L eafy vegetables: Broccoli; Chinese broccoli (gai lon); broccoli raab (rapini); Brussels sprouts; cabbage; Chinese cabbage (bok choy); Chines e cabbage (napa); Chinese m ustard (gai choy); cauliflower; cavalo broccolo; collards; kale; kohlrabi; mizuna ; mustard greens; m ustard 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 Che mistry and Residue Data DP#: 37116 2



### Page 7 of 29 Table 3. Summary of Directions for Use of Ranman® 400SC (EPA Reg. No. 71512 - 3) Foliar (For the control of Dow ny mildew diseas e) 3 2.75

(0.072) 5 13.75 (0.36) 7 to 10 0 Begin spray when disease is first seen or weather and dow ny 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 ( f or control of Dow ny mildew ease) 6 2.1 to 2.75

(0.054 to 0.0 (0.0 71) 6 16.5 (0.426) 7 to 10 3 Begin spray when disease is first se en or weather and dow ny mildew disease pressure are expected to initiate a disease epidemic. Use longer interval for preventive or low

disease pressure. Use water sp r ay of at least 100 gal/A . R esistance m anagem ent : Do not apply mo re 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 fu ngicides having different modes of action before applying additional RANMAN ® 400SC . 2 Soil Incorporation: Alternatively, if desired and for soil with low infiltration rate s, apply 20 fl oz per acre in a minimum bandwidth of 9 inches along the planting ro w 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 U se 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 m anagem ent : Do not apply more than five applications of RANMAN ® 400SC per crop. Alternate foliar sprays of RANMAN ® 400SC with a fungi cide 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 m anage me nt : 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 Che mistry and Residue Data DP#: 37116 2



### Page 8 of 29 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 s oil incorporation of Ranman ® 

### 400 SC at the rate of 20 fl oz per acre before transplant is included i n the supplemental label as an alternative to the post transplant soil dren ch application. N o data have been submitted to support th e soil incorporation method. However, HED notes that incorporation of Ranman 400SC into the soil (before transplant) is already o n the current label and ha s been used o n crop field studies from earlier petitions (PP#8E7427). N o 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 metabolis m 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 c rop in which the cyazofamid test substances were radiolabeled in either the phenyl ring ([benzene 14 

### C]cyazofamid) or in the fourth position of the imidazole ring ([imidazole 14 

### C]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 m etabolism studies in plants indicate d that the parent and CCIM are the major residues (>10% TRR). There are no specific toxicity con cerns for all other minor metabolites. T he 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 ri sk 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 stu dies 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 radio labeled in either the phenyl ring ([benzene 14 

### C]cyazofamid) or in the fourth position of the imidazole ring ([imidazole 14 

### C]cyazofamid). These studies have been reviewed and deemed acceptable pending submission of additional information pertaining to samp le 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 co mpletely recovered (>80% recovery ) usingCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 9 of 29 FDA’s Multi r esidue Protocol D (without cleanup). In addition, an acceptable HPL C/UV method is available for use as a single analy te confirmatory

method. Quantification of the re sidues of cyazofamid and CCIM in the current crop field trials was achieved by

liquid chromatography with tandem mass spectrometric detectio n (LC/MS/MS ) as described in “Independent Laboratory Validation of the Residue Method for IKF - 916 and CCIM in T omatoes ” , Document Number 013033 - 0, Py xant L ab s 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 (LLM V) 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 ex traction method used for b roccoli, cabbage, mustard greens and spinach is described briefly as follows : Five gram sample s 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. Th e 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 1 0 ml ) using a rotary evaporator in a water bath at about 45 o 

### C. The r esidues are disso l ved in 20% ACN: water, passed through a N exus solid phase extraction column (SPE) and eluted with 60% ACN: water. C yazofamid and CCIM residues are quantified by LC /MS/MS. For h op 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 separate ly for the residues of cyazofamid and CCIM. For cyazofamid , the fraction i s concentrated to dry ness , 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 dry ness , diluted to 12.5 ml with 50 : 50 ACN: water and analysed by L C/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 Poly mer 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 L C/MS/MS . The calculations for LOQs and LODs f or 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 an d its metabolites were submitted previously

in conjunction with PP# 1F06305. T he Agency previously

concluded that the FDA Multi r esidue Method, Protocol D (without cleanup) me e t s 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 forCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 10 of 29 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 sta bility study w as conducted using two sets of untreated control crop field samples which were fortified separately with cyazofamid and CCIM and stored at < - 20 o 

### C. B roccoli, cabbage, mustard greens and spinach samples were fortified at 1.0 ppm and stored fo r 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. Sum mary of Storage Conditions and Durations of Samples from the Crop Field Trials. Matrix (RAC) Analytes Stor age Temp. ( o C) 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 cy zofamid are stable in cabbage, mustard greens, s pinach 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 remin ded that zero day data should be submitted in future petitions as require d in Guideline 860.1300.Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 11 of 29 860.1400 Water, Fish, and Irrigated Crops There are no proposed/registered uses that are relevant to this guideline topic . 860.1460 Food Handling The re 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 Reference s : 47870701.de r.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 a i/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 ap plications were made. A minimum of about 2 pounds of broc c oli 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 mi nutes of sampling and kept frozen until prepared f o r analysis. Cabbage DER Reference s : 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 (PH I) using a non ionic 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 eac h plot, cut into halves or quarters and frozen within 40 min of sampling. Wrapper leaves were also retained. All samples were kept frozen until prepare d for analysis.Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 12 of 29 Mustard Greens DER Reference s : 478707 03 .der.doc 

### Nine trials were conducted in the Uni ted 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 site s MD06, TX*15, and CA44 , where foliar directed applications were made. Two treated and tw o untreated control samples were collected f

rom 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 Reference s : 478707 04 .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 pound s of above ground leaves were collected from a minimum of 12 plants per treatment and frozen within 25 minutes. Samples were kept fro ze n from sampling until prepared for extraction and analysis. Hops DER Reference s : 478707 05 .der.doc 

### T hree field trials were conducted in the United States encompassi ng 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 afterCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### 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 analy zed 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 a fter 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. Inspinach, a fter five foliar applications totaling 0.347 - 0.366 lb ai/A a pplied at 7 (± 1) day

intervals and 0 - day PHI , the maximum total residues (cyazofamid and CCIM) detected in the leaves w ere 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 w ere 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 require d 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) Cyazo f amid (ppm) CCIM

(ppm) Combined

Residues 1 Broccoli 1 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/Hotvi lle, 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 Cabbage 2 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 <0.0 1, <0.01 0.305, 0.295Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 14 of 29 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/Bri dgeton, 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* 0 5/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/20 06 5 Cabbage/ Blue Vantage Head with

Wrapper Leaves 0.476 0 0.12, 0.13 <0.01, <0.01 0.125, 0.135 Mustard Greens 3 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*0 6/Tifton, GA/20 06 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 Green s (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 (Mu stard)/ 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, 0.029Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 15 of 29 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/ Free ville, 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/ Bloomsdal e 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/ 20 07 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 c ombined r esiduesCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### 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. HAFT 1 Median 2 (STMdR) Mean 2

(STMR) Standard

Deviation 2 Bro c coli Broccoli Flower Head Cyazofamid 0.479

– 0.552 0 12 0.18 0.91 0.84 0.36 0.41 0.22

CCIM NA 3 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 NA 3 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 NA4 0 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 Spin ach 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 Spin ach Leaves CCIM NA 3 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 0.0021Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 17 of 29 Spinach Leaves CCIM NA 4 2 0.013 0.016 0.0145 0.0145 0.0145 0.002 1 Hops Hop Cones Cyazofamid 0.425 - 0.443 2 - 4 6 2.5 6.9 6.3 3.2 4.0 1.9

CCIM NA2 2 - 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, an d standard deviation 3 Not Applicable 

### Conclusion . The submitted crop field stud ies are adequate to support the proposed minor uses. The studies were conducted consistent with standard agricultural practices as per proposed use patte rn . 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, whi ch did not have any adverse impact on the stud ies . 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 Propo sed 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. T olerances are currently established in 40 CFR §180.601 (a) for the combined residues o f 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. 4 0 ppm . In addition, tolerances with regional registration s 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, 2 009) 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 metabolite s 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) - 1 H - imidazole - 1 - sulfonamide and its metabolite, 4 - chloro - 5 - (4 - methylp henyl) - 1 H
- 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 t olerance 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 Che mistry and Residue Data DP#: 37116 2



### 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: (m emorandum, 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 le vel as the Brassica , L eafy Greens, Crop Subgroup 5B at 12.0 ppm. The recommended tolerances for spinach and h ops are 9 and 10.0 ppm, respectively . The recommended tolerances are listed in Table 7. Canada has established maximum residue limit s (MRL) for residues of c yazofamid in/on several commodities, but has not established maximum residue limits for the commodities of this petition. No maximum residue limi t s (MRL s) for residues of c yazofamid have been established

by the Codex Alimentarius Commission . Table 7 . Tolerance Sum ma ry for Cyazofamid . Commodity Proposed Tolerance (ppm Existing

Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition 40 CFR 180. 601 (a) Brassica , head & s tem , c rop s ubgroup 5A 1.2 1.2 Brassica , l eafy greens, c rop s ubgroup 5B 12.0 12.0 H ops 10.0 10.0 S pinach 9.0 9.0 Turnip greens 12.0 12.0 Until the regulations have been finalized in the Federal Register to mo ve turnip greens from the leaves of root and tuber vegetables crop group (gro up 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

1 Memorandum, 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 Analy tical Chemistry

and Residue Data From: Amelia Acierto To: Janet Whitehurst/Cy nthia Giles - Parker, PM Team #22 Date: 2/20/20 04Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### 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 Analy tical 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 L imit Status sheet Appendix II - Tolerance Assessment Calculations Template Version April 2008Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 20 of 29 APPENDIX I 

# INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 4 - Chloro - 2 - cyano -N,N

dimethyl - 5 - (4 - methylphenyl) - 1 H

imidazole - 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# 9 E7 615 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) - 1 Himidazole - 1 - sulfonamide and its metabolite, CCIM, 4 - chloro - 5 - (4 - methylphenyl) - 1 H
- 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) - 1 H

- imidazole - 1 - sulfonamide, including the metabolite 4 - chloro - 5 - (4 - methylphenyl) - 1 H
- 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, 3/6/2010Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### 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, th e minimum of the 95% upper confidence limit (UCL) on the 95 th 

### percentile and the point estimate of the 99 th 

### 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% UCLon 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 89 th 

### percentile was selected as the tolerance value (distribution - free method). The rounding procedures specified in the SOP were also use d. Brassica, Crop Subgroup 5A The dataset used to establish tolerance s for residues of Cyazofamid on Brassica Crop Subgroup 5 A consisted of field trial data for the representative crops : broccoli and cabbage and represented application rates of 0.48 5 - 0.50 6 lb ai/A ( 1 soil drench + 5 - 6 foliar applications) with a PHIof 0 day . As specified by

the SOP, the field trial application rates and PHI s 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 (0.0 1 ppm). The dataset for w as 12 samples for broccoli, and 18 samples f or cabbage . The dataset for each crop was entered i nto 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 - Fr ancia test statistic (F igures 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 toleran ces 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 dre nch + 5 - 6 foliar applications) with a PHI of 0 day . As specified by the SOP, the field trial application rates and PHI s 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 theCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### 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 rec ommended 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 1 2 ppm is recommended for individual tolerances. Spina ch The dataset used to assess a tolerance for Cyazofamid residues in/on spinach consisted of field trial data and represented application rate of 0.361 lb ai/A (5 foliar applications) with a PHI of 0 day . As specified by

the SOP, the field trial applicat ion rates and PHI s 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 w as 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 reaso nably lognormal. The results from the approximate Shapiro Francia 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. Hop s The dataset used to assess a tolerance for Cyazofamid residues in/on hops consisted of field trial data and represented application rates of 0.4 36 lb ai/A (6 foliar applications) with a PHI of 0 day . As specified by

the SOP, the field trial applicatio n rates and PHI s 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 p pm). 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. Th e results from the approximate Shapiro - Francia test statistic (Figure II 4 ) confirmed that the assumption of lognormality should not be rejected. Using the tolerance spreadsheet, the recommended tolerance for hops is 1 0 ppm.Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 23 of 29 Table I . Residue data u sed to calculate tolerance for cyazofamid residues on broccoli, cabbage and mustard greens. Br assica Crop Subg roup 5A Br assica Crop Subg roup 5 B 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 4 7 5 28401 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 2.1 4 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. 77Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 24 of 29 Figure I - 1. Lognorm al 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

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000

0.5000

0.2500

0.1250 y = 0.5067x - 0.9989 R 2 = 0.9609

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

Fig ure I - 2. Tolerance spreadsheet sum ma ry 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+3SDCyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 25 of 29 Figure I - 3. Lognorm al Probability Plot of Cyazofamid Residues in/on Cabbage Following One Post Transplant Drench and Five to Six Foliar Appl ications of RanMan 400 SC at a Total Rate of 0.485 lb ai/A.

Figure I - 4 . Tolerance spreadsheet sum ma ry 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

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000

0.5000

0.2500

0.1250

0.0625 y = 0.594x - 1.2669 R 2 = 0.9642

PercentilesConcentrations EPA Cyazofamid Cabbage 0 0.485 lb ai/A IR-4Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 26 of 29 Figure I - 5. Lognorm al Probabili ty 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 sum ma ry of cyazofamid field trial data for m ustard 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

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 7.0000

3.5000

1.7500

0.8750 y = 0.4915x + 1.2757 R 2 = 0.9374

PercentilesConcentrations EPA Cyazofamid Mustard Greens 0 0.484 lb ai/A IR-4Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 27 of 29 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 0.4 36 lb ai/A Submitter: IR - 4 IR - 4 MRID Citation: MRID 4752840 4 MRID 4752840 5 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 5.25Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 28 of 29 Figure II - 1. Lognorm al Probability Plot of Cyazofamid Residues in/on Spinach Following Five Foliar

Applications of RanMan 400 SC at a Total Rate of 0.3 61 lb ai/A.

Figure II - 2. Tolerance spreadsheet sum ma ry 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

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 7.0000

3.5000

1.7500

0.8750 y = 0.4379x + 1.0927 R 2 = 0.975

PercentilesConcentrations EPA Cyazofamid Spinach 0 0.361 lb ai/A IR-4Cyazofamid Summary of Analytical Che mistry and Residue Data DP#: 37116 2



### Page 29 of 29 Figure II - 3. Lognorm al 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 sum ma ry of cyazofamid field trial data for hops. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 8.0000

4.0000

2.0000 y = 0.3852x + 1.3874 R 2 = 0.8484

PercentilesConcentrations 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