Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 1 of 27 **UNITED STA**

**TES ENVIRONMENTA L PROTECTION A** **GENCY WA** **SHINGTON, D.C. 20460 OFFICE OF**  **CHEMICAL SAFETY AND**  **POLLUTION PREVENTION MEMORANDUM**  **Date :**  M ay 

### 3 , 2012 **SUBJECT: Cyprodinil**  **. Amended Use.**  Expansions of Existing Crop Group/Rep resentative

Commodity

Uses to Numerous Crop Subgroups , Adding Use on Leafy Petiole Subgroup 4B, and Adding Use on the Remaining Crops in Fruiting Vegetables Group 8 - 10 . **Summary of Analytical Chemistry and Residue Data. PC Code:**  288202 **DP Barcode:** 3 8 95 54 & 391680 **Decision No.:** 447576 & 448809 **Registration No s**  **. :**  100 - 828 , 100 - 953, and 100 - 1317 **Petition No.:** 1E7854 & 1E7869 **Regulatory Action:** Amended Section 3 **Risk Assessment Type:** NA **Case No.:** 7025 **T XR No.:**  NA **CAS No.:** 121552 - 61 - 2 **MRID No.:** 4 8437401

– 05 ; 48478501 **40 CFR:** 180. 5 32 **FROM:** Thurston G. Morton , Chemist

Risk Assessment Branch 4 Health Effects Division (7509 P ) **THROUGH:** Susan V. Hummel , Chemist, S enior Scientist

Elissa Reaves, PhD., Branch Chief Ris k Assessment Branch 4 Health Effects Division (7509 P ) **TO:** Rebecca Daiss, Risk Assessor

Risk Assessment Branch 4 Health Effects Division (7509P) and Li s a Jones/ Shaja Joy

ner , RM20 Fungicide Branch Registration Division (7505 P )Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 2 of 27 **Executive Summary** Under PP#1E785 4 , Interregional Research Project No. 4 (hereafter referred to as IR - 4), on behalf of the Agricultural Experiment Stations, is requesting the establishment of tolerances fo r residues of cy prodinil [ 4 - cyclopropyl - 6 - methyl -N - phenyl - 2 - py

rimidinamin ] in/on the following raw agricultural commodities:

Onion, bulb subgroup 3 - 07A..... ................................ .............. 0.6 ppm Onion, green subgroup 3 - 07B ................................ ................... 4.0 ppm Caneberry

subgroup 13 - 07A........................................10 ppm Bushberry subgroup 13 - 07B ................................ ......... .........3.0 ppm Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit.....2.0 ppm Lo w growing berry

subgroup 13 - 07G, except cranberry .......... 5.0 ppm Dragon fruit ................................ ................................ .............. 2.0 ppm Fruit, pome, group 11 - 10 ................................ .......................... 1. 7 ppm Vegetable, fruiting, group 8 - 10 ................................ ................. 1.3 p pm Vegetable, leafy, except brassica, subgroup 04A.................. 40 ppm Inaddition, IR - 4 is requesting to amend the currently established tolerance for residues of cy prodinil in/on Citrus oil by decreasing it to 60 ppm. Citrus oil............................................................... 60 ppm Inaddition, IR - 4 is requesting the removal of the currently established tolerances for residues of cy prodinil in/on Onion, bulb (0. 6 ppm); Onion, green ( 4. 0 ppm); Caneberry subgroup 13A ( 10.0 ppm); Bushberry

subgroup 13B ( 3 .0 ppm); Juneberry (3.0 ppm); Li ngonberry

(3.0 ppm); Salal (3.0ppm); Grape (2.0 ppm); Strawberry (5.0 ppm); Fruit, pome (1.7 ppm); Tomatilla (0.45 ppm); Tomato (0.45 ppm); and Leafy greens subgroup 4A, except spinach ( 30 ppm). Inconjunction with PP#1E78 54 , IR - 4 is requesting an amend ed Section 3 registration for Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953 ), a 37.5% water dispersible granule ( WDG ) formulation of cy

prodinil ; VanguardTM WG (EPA Reg. No. 100 - 828 ), a 75 % water dispersible granule (WDG) formulation ; and In spire Super TM Fungicide (EPA Reg. No. 100 - 1317), a 2.09 lb ai/gallon emulsifiable concentrate to the remaining fruiting vegetable crops and to spinach . In support of this new use, IR - 4 has submitted new pepper and spinach magnitude of the residue data for cy

prodinil using the WDG formulation of cy prodinil at the proposed use rate.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 3 of 27 Inaddition, IR - 4 is requesting amendments for the Section 3 registrations for VanguardTM WG (EPA Reg. No. 100 - 828), Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953), and In spire Super TM Fungicide (EPA Reg. No. 100 - 1317) to expand currently registered foliar uses for bulb vegetables, fruiting vegetables, berry and small fruits , dragon fruit, pome fruits, and leafy vegetables to include the additional commodities specified under the following new crop groups/subgroups, respectively : Onion, bulb subgroup 3 - 07A , Onion, green subgroup 3 - 07B , Caneberry

subgroup 13 - 07A, Bushberry subgroup 13 - 07B , Small fruit vine climbing subgroup 13 - 07F, except fuzzy

kiwifruit , Dragon fruit , Vegetable, fruiting, group 8 - 10, Vegetable, leafy, except brassica, subgroup 04A, Pome Fruits Group 11 - 10, and L ow growing Berry Subgroup 13 - 07G, Except Cranberry . No amendments to the use patterns (i.e., maximum use rates, retreatment intervals, preharvest intervals, use of adjuvants, etc.) on the subject crops have been proposed. No new residue chemistry data were submitted to support these uses. Instead the petitioner wis hes to rely

on previously

submitted residue chemistry data which support the currently registered uses of cy

prodinil . **One of the products**  **(EPA Reg. No. 100 -**  **1317) addressed herein contain**  **s a second active**  **ingredient ( difenoconazole**  **) and another product (E**  **PA Reg. No. 100 -**  **953) contains fludioxonil**  **. D**  **ifenoconazole and fludioxonil are addressed under separate reviews. The subject review addresses the proposed uses and supporting data for**  **cyprodinil only.**  Under PP#1E7869, Sy

ngenta Crop Protection, Inc, is requesting the establishment of tolerances for residues of cy

prodinil [4 - cyclopropyl - 6 - methyl -N - phenyl - 2 - py

rimidinamin] in/on the following raw agricultural commodities:

Leafy petiole subgroup 04B ................................ .................... 30 ppm Sy ngenta Crop Protection, Inc. is requesting a Sec tion 3 request for the use of V angard ®WG Fungicide (EPA Reg. No. 100 - 828) and Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953) on the leafy

petiole subgroup 04B . Insupport of this new use, Sy ngenta has submitted celery magnitude of the residue data for c yp rodinil using the WDG formulation of cy prodinil at the proposed use rate. **Note:** Th is review only addresses the proposed uses for cy prodinil only . Related issues for co ingredient fludioxonil in Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953) will be discussed in a separate memo. Cy prodinil was applied in four applications of Switch 62.5 WGTM at a rate of approximately 0.5 lb cy prodinil a.i. /A per application with a 6 - 8 day retreatment interval (RTI) for a maximum seasonal rate of 2. 2 lb a.i./A to celer y . Celery samples were harvested at a PHI of 0 days. The nature of cy

prodinil residues in plants is understood based on adequate metabolism studies on apple, peach, potato, tomato, and wheat. O nly residues of parent cy

prodinil need to be included in the tolerance expression and considered for risk assessment for plant commodities. The nature of cy

prodinil residues in ruminants is also understood based on an adequate goat metabolism study . The residues of concern in ruminants are cy prodinil and its hydroxylated metabolite CGA - 304075 (free and conjugated). No poultry metabolism study

is available , butCyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 4 of 27 HED has conclude d that none is required for this action since there are no poultry feed stuffs associated with the proposed new use of cy prodinil o n le afy

petiole group 4B . Adequate HPLC/UV methods (Methods AG - 631 and AG - 631B) are available for enforcing tolerances of cy

prodinil in/ on plant commodities . The limits of quantitation ( LOQ ) for the plant methods range from 0.01 to 0.05 ppm depending on the commodity. An adequate LC/MS method (GRM010.01A) is also available for enforcing tolerances of cy prodinil residues in livestock commodities. The method L OQ for this method is 0.02 ppm for the combined residues of cy prodinil and its metabolite CGA - 304075 (free and conjugated), expressed as parent. Inthe submitted field trial study, residues of cy prodinil in/on spinach, pepper, and lemon were determined with a method using high performance liquid chromatography with a tandem mass spectrometer (LC/MS/MS), which is a modified version of the HPL C/UV Sy ngenta Method AG 631B, “Analy

tical Method for the Determination of Residues of CGA - 219417 in Crops by High Performance Liquid Chromatography with Column Switching .” Sy ngenta Methods AG - 631 and AG - 631B are the current tolerance enforcement method s for determining cy prodinil in plant commodities. Inthe submitted field trial study for celery, residues were analy zed by using a high performance liquid chromatography method with tandem mass spectrometric detection (LC /MS/MS), Sy

ngenta method AG - 597 B . This method is actually the current tolerance enforcement method for fludioxonil in plant commodities and was modified by NCLto enable simultaneous extraction of both cy prodinil and fludioxinil from celery obviating S yn genta Method AG - 631B which is the current tolerance enforcement method for determining cy prodinil in plant commodities . Peppers, spinach, lemon, lemon dried pulp, lemon juice, lemon oil, and celery samples were stored frozen ( - 20°C ± 10 °C ) for up to 9, 22 , 3.5, 4.8, 5.6, 10.3, and 7.2 months before analysis , respectively . Demonstrated storage stability for the submitted field trial samples include 9 months for peppers, 5.8 months for dried lemon pulp, 5.9 months for lemon juice, and 10.6 months for lemo n oil. T he stability of cy prodinil has been demonstrated in a variety of other crops, including mustard greens for 20 months and grape, wine, apple, wheat (ear and stalk), strawberry, and potato for up to 2 years (D233182, G. Kramer, 02/20/98; D288706, T. Bloem ,7/24/03) . Therefore, the submitted field trial data are supported by acceptable storage stability data. The HAFT residue level of cy prodinil in bell peppers, non - bell peppers, and spinach resulting from four applications for a seasonal rate of 1. 3 lb cy prodinil a.i. /A was 0. 682 , 0. 668 , and 32.1 ppm , respectively . Maximum residue levels of cy prodinil were 0. 697 ppm in bell pepper , 0. 818 ppm in non - bell pepper , and 37 ppm in spinach . There are an adequate number of bell pepper, non - bell pepper, and spinach field trial s with acceptable field trial from representative geographical locations. The trial s were conducted with Switch 62.5WG to support the requested crop group tolerance, for a 0 - day PHI . No adjuvant or surfactant was used in the bell pepper or non - bell pepper field trials. Non - ionic surfactant or a crop oil concentrate were used in the spinach field trials. The HAFT residue level of cy prodinil in celery

resulting from four applications for a seasonal rate of 2.2 lb cy

prodinil a.i./A wa s 17ppm. Maximum residue levels of cy prodinil w ere 17 ppm in celery . There are an adequate number of celery field trials with acceptable field trial fromCyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 5 of 27 representative geographical locations. The trials were conducted with Switch 62.5WG to support the requested crop group tolerance, for a 0 - day PHI . Non - ionic surfactant or a crop oil concentrate were used in the spinach field trials. The OECD Maximum Residue L imit Calculator was used to determine appropriate tolerance level s . A tolerance level of 50 p pm for Vegetable, leafy, except brassica, subgroup 4A and a tolerance of 1. 5 ppm for the Vegetable, fruiting, group 8 - 10 is appropriate to cover the proposed amended uses of cy

prodinil. **Note that these tolerance levels are different than those proposed by**  **the registrant .**  **This is due to calculating the MRLs with the OECD MRL**  **calculator and harmonizing with**  **proposed Canadian MRLs.**  There are currently

established Codex maximum residue limits (MRL s) for residues of cy prodinil in/on eggplant (0.2 mg/kg), pepp ers, sweet (0.5 mg/kg), and tomato (0.5 mg/kg) . Neither Codex n or Canada ha s MRL s for the leafy petioles crop group. Itis not possible to harmonize with Codex MRL s for residues of cy prodinil in/on eggplant, peppers, and tomato. It is not possible to harmonize with Codex and Canadian MRL s for residues of cy

prodinil in/on these commodities because the US is recommending the establishment of a fruiting vegetable group 8 tolerance at 1. 5 ppm, and removal of the existing 0.45 ppm tolerance in/on tomato and t omatillo, along with the 1.0 ppm tolerance on tomato paste. Canada will be establishing an MRL on the fruiting vegetable crop group also . T here are no tolerances established in Mexico. **Regulatory Recommendations and Residue Chemi stry Deficiencies**  HED has examined the residue chemistry database for cy

prodinil . With regards to cy prodinil for PP#1E78 54 , pending submission of a revised Section B (see requirements under Directions for Use) and a revised Section F (see requirements un der Proposed Tolerances), there are no residue chemistry issues that would preclude granting amended registrations for VanguardTM WG (EPA Reg. No. 100 - 828), Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953), and In spire Super TM Fungicide (EPA Reg. No. 100 - 1 317) to expand currently registered foliar uses for bulb vegetables, fruiting vegetables, berry and small fruits, dragon fruit, pome fruits, and leafy vegetables to include the additional commodities specified under the following new crop groups/subgroups, respectively : Onion, bulb subgroup 3 - 07A , Onion, green subgroup 3 - 07B , Caneberry

subgroup 13 - 07A, Bushberry subgroup 13 - 07B , Small fruit vine climbing subgroup 13 - 07F, except fuzzy

kiwifruit , Dragon fruit , Vegetable, fruiting, group 8 - 10, Vegetable, lea fy , except brassica, subgroup 04A, Pome Fruits Group 11 - 10, and L ow growing Berry Subgroup 13 - 07G, Except Cranberry or es tablishment of tolerances for residues of cy prodinil only

in/on the following commodities:Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 6 of 27 Onion, bulb , subgroup 3 - 07A..... ................................ ............. 0.6 pp m Onion, green , subgroup 3 - 07B ................................ .................. 4.0 ppm Caneberry

subgroup 13 - 07A........................................10 ppm Bushberry

subgroup 13 - 07B ................................ ......... .........3.0 ppm F ruit , s mall vine climbing , except fuzzy kiwifruit , subgroup 13 - 07F, .....2.0 ppm B erry, l ow growing subgroup 13 - 07G, except cranberry .......... 5.0 ppm Dragon fruit ................................ ................................ .............. 2.0 ppm Fruit, pome, group 11 - 10 ................................ .......................... 1.7 ppm Vegetable, fruiting, group 8 - 10 ................................ ................. 1. 5 ppm Vegetable, leafy, except brassica, subgroup 4A.................. 5 0 ppm Citrus, oil............... ...... ...... ... ..................................60 ppm The approved amended registrations for VanguardTM WG (EPA Reg. No. 100 - 828), Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953), and In spire Super TM Fungicide (EPA Reg. No. 100 - 1317) are limited to expansions to add the commodities specified under the new crop groups/subgroups and do not include substantiv e changes to currently registered use patterns (i.e., maximum use rates, retreatment intervals, preharvest intervals, use of adjuvants, etc.). With regards to cy

prodinil for PP#1E7869 , pending submission of a revised Section F (see requirements under Proposed Tolerances), there are no residue chemistry issues that would preclude granting an amended registration for Vangard®WG Fungicide (EPA Reg. No. 100 - 828) and Switch 62.5 WGTM Fungicide (EPA Reg. No. 100 - 953) to permit a new use on leafy petioles subgroup 4B or establishing a t olerance for residues of cy prodinil only

in/on the following commodities: Leaf petioles subgroup 4B..............................30 ppm A human health risk assessment i s forthcoming. **Notes to PM: 1.**  **A tolerance of 60 ppm was listed for citrus oil in the Notice of Filing but a tolerance of 100 ppm was listed in Section F of the petition**  **. 2**  **. Use information was taken from Section B of the petition.** Tolerances sho uld be revised, as needed, to reflect the correct commodity definitions as specified in Table 8 . These recommendations are made concerning cy prodi nil only . I ssues concerning co - ingredient difenoconazole or fludioxonil will be discussed in a separate me mo. A human heath risk assessment is forthcoming.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 7 of 27 **Background** Cy prodinil is an anilino - py

rimidine fungicide used to control various plant diseases on a wide variety of fruit, nut, vegetable and herb crops. Tolerances for residues of cy prodinil have been established in/on a variety of crop commodities at levels ranging from 0.02 - 340 ppm [40 CFR §180.532] . Tolerances have also been established at 0.02 ppm for cy prodinil residues in meat by products of cattle, goats, horses, and sheep. No tolerance is established for poultry by products. The chemical structure, nomenclature, and physicochemical properties of the technical grade of cy prodinil are presented in Tables 1 and 2. **Table 1. Cyprodinil Nom**  **enclature.** Compound

N N

C H3 N H

Common name Cyprodinil Company experimental name CGA219417 IUPAC name (4 - cyclopropyl - 6 - methyl

– pyrimidin - 2 - yl) - phenyl - amine CAS name 2 - pyrimidinamine, 4 - cyclopropyl - 6 - methyl -N - phenyl CAS registry number 121552 - 61 - 2 End - use product (EP) 75% water - dispersible granule formulation ( Vangard® WG Fungicide; EPA Reg. No. 100 - 828) ; a multiple active ingredient (MAI) end - use product (Inspire Super TM Fungicide; EPA Reg. No. 100 - 1317) formulated as an emulsion [oil] in water (EW), containing 8.4% difenoconazole and 24.1% cyprodinilCyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 8 of 27 **Table 2.**  **Physicochem ical Properties of Technical Grade of Cyprodinil.**  Parameter Value Reference Melting point/range 75.9 C DP#s 345970 and 345182, W. Cutchin, 6/4/08 pH 9.5 at 25 C (1% aqueous dispersion) Density 1.21 g/cm3 at 20 C Water solubility (mg/L at 25 C) pH 7.6 16 pH 5 20 pH 7 13 pH 9 15 Solvent solubility (g/L at 25 C) ethanol 160 acetone 610 toluene 460 n - octanol 160 n - hexane 30 Vapor pressure 3.8 x 10 - 6 mm Hg at 25 C Dissociation constant, pKa 4.44 at 20 C Octanol/water partition coefficient, Log(KOW) at 25 C 3.9 at pH 5 4.0 at pH 7 4.0 at pH 9 UV/visible absorption spectrum (molar absorption coefficients for the absorbance maximum) 29,200 l/mol ·cm at 270.8 nm (neutral) 29,200 l/mol ·cm at 251.6 nm (acidic ) 29,200 l/mol ·cm at 316.8 nm (acidic) 28,400 l/mol ·cm at 270.8 nm (basic)Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 9 of 27 **860.1200 Directions for Use Table**  **3. Summary of**  **Proposed Directions for Use of**  **Cyprodinil** Applic. Timing, Ty pe, and Equip. Formulation

[EPA Reg. No.] Appli c.

Rate (lb ai/A) Max. No.

Applic. per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations Spinach Broadcast foliar Ground/Aerial/ Chemigation Vangard

WG 75% W DG [100 - 828] 0.114 4 0.34 0 A minimum retreatment interva l (RTI) of 7 days is proposed.

Broadcast foliar Ground Only Switch

62.5WG 37.5% W DG [100 - 953] 0.33 4 implied 1.31 0 A minimum retreatment interval (RTI) of 7 - 10 days is proposed. Celery Broadcast foliar Ground/Aerial/ Chemigation Vangard WG

75% W DG [ 100 - 828] 0.33 2 by aerial 4 implied 1.3 0 A minimum retreatment interval (RTI) of 7 - 10 days is proposed. Broadcast foliar Ground Only Switch

62.5WG 37.5% W DG [100 - 953] 0.33 4 implied 1.31 0 A minimum retreatment interval (RTI) of 7 - 10 days is proposed. Pepper Broadcast foliar Ground/Aerial/ Chemigation Vangard WG

75% W DG [100 - 828] 0.33 2 by aerial 4 implied 1.3 0 A minimum retreatment interval (RTI) of 7 - 10 days is proposed. Broadcast foliar Ground Only Switch

62.5WG 37.5% W DG [100 - 953] 0.33 4 impli ed 1.31 0 A minimum retreatment interval (RTI) of 7 - 10 days is proposed. Broadcast foliar Ground/Aerial/ Chemigation Inspire Super

2.09 lb/gal EW [100 - 1317] 0.33 2 by aerial 4 implied 1.3 0 A minimum retreatment interval (RTI) of 7 - 10 days is proposed. Conclusions . The proposed use directions are sufficient to allow for evaluatio n of the available residue data. The submitted field trials for spinach and celery used adjuvants , while the field trials for peppers did not. Thus, a revised section B must be submitted prohibiting the use of adjuvants for peppers . Inaddition, no pepper field trials were conducted with the Inspire Super EW formulation. Therefore, peppers must be removed from the label for Inspire Super.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 10 of 27 **860.1300 Nature of the Residue -**  **P lants**  DP# 2 19794 , G. Kramer, 2/ 13 /9 6 DP# 233182, G. Kramer, 2/20/98 MARC Decision Memo, DP# 243198, G. Kramer, 3/11/98 The nature of the residue in plants is adequately understood based on acceptable metabolism studies on apple, peach, potato, tomato, and wheat. These studies indicated that cy prodinil is metabolized primarily

by hydroxylation followed by sugar conjugation. Cleavage of the amino bridge, opening of the py rimidine ring, opening of the cyclopropyl ring and formation of thiolactic acid con

jugates are minor pathways. Incorporation into starch was observed in potato tubers and wheat grain. The MARC reviewed these studies and determined that the residue of concern, for purposes of tolerance enforcement and risk assessment, is cy prodinil . **8 60.1300 Nature of the Residue**  **- Livestock**  DP# 233182, G. Kramer, 2/20/98 MARC Decision Memo, DP# 243198, G. Kramer, 3/11/98 DP# 345970 and 345182, G. Kramer, 6/4/08 DP# 362486, J. Stokes, 9/15/09 The nature of the residue in ruminants is adequately unde rstood based on acceptable lactating goat metabolism studies using [ 14 C - phenyl] and [ 14 C - py rimidinyl ] cy

prodinil . T he metabolism of cy prodinil in ruminants proceeds predominantly via hydroxylation followed by conjugation with sulfuric and glucuronic acid. Breakdown of the py rimidinyl ring was seen only in the liver and resulted in Metabolite L 1. Cleavage of the amino bridge between the phenyl and the py rimidinyl rings was only

a minor reaction as indicated by the small amounts of CGA 249287 found in the liver and kidneys of goats dosed with [ 14 C - py rimidinyl]cy

prodinil. HED originally concluded that were no cy prodinil metabolites of toxicological or regulatory concern in ruminant milk and tissues based on the dietary burden associated with the registered cy prodinil uses at that time (362486, J. Stokes, 09/15/09; 378920, B. Cropp - Kohlligian, 10/27/10). However, HED noted that if future uses significantly increase the potential livestock dietary burden, then a new cy

prodinil feeding study

would be required in which residues of cy prodinil and CGA 304075 (both free and conjugated) are determined. ARIA subsequently has concluded that the residues of concern for both risk assessment and the tolerance definition should include the combined residues of cy prodinil and metabolite CGA - 304075 ( free and conjugated) , expressed in parent equivalents. A poultry metabolism for cy

prodinil has not been submitted and none has been requested since the potential dietary

exposure of poultry

to cy prodinil residues is extremely l ow ( estimated at 0.005 ppm based on canola meal consumption) . Since there are no poultry feed s tuffs associated with the proposed amended use s of cy prodinil on tree nuts , then at this time a poultry metabolism study is not need ed and the uses cannot be con sidered “Category 3 for poultry . However, if future crop are added that produce poultry feedstuffs, then HED may require a study .Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 11 of 27 **860.1340 Residue Analytical Methods** Enforcement m ethods. Adequate HPLC/UV methods with column switching (Sy ngenta Methods AG - 631 and AG - 631B ) are available for enforcing tolerances of cy prodinil on plant commodities. The LOQs for these methods range from 0.01 to 0.05 ppm depending on the plant commodities . Method AG - 631B also contains proced ure s for confirmatory

analysis by GC/NPD . An adequate HPLC/MS method (GRM010.01A) is also available for enforcing tolerances in livestock commodities. This method determine s residues of both parent and the metabolite CGA - 304075 ( free and conjugated), expressed as parent. The L OQ is 0 .01 ppm for each analy te for a combined LOQ of 0.02 ppm. Data collection methods. Inthe submitted field trial study, residues of cy prodinil in/on spinach, pepper, and lemon were determined with a method using high performance liquid chromatography

with a tandem mass spectrometer (LC/MS/MS), which is a modified version of the HPL C/UV Sy

ngenta Method AG - 631B, “Analy tical Method for the Determination of Residues of CGA - 219417 in Crops by High Performance Liquid Chromatography with Column Switching .” Sy

nge nta Methods AG - 631 and AG - 631B are the current tolerance enforcement method s for determining cy prodinil in plant commodities. Inthe submitted field trial study for celery, residues were analy zed by using a high performance liquid chromatography method wi th tandem mass spectrometric detection (L C /MS/MS), Sy ngenta method AG - 597 B . This method is actually the current tolerance enforcement method for fludioxonil in plant commodities and was modified by

NCLto enable simultaneous extraction of both cy prodinil and fludioxinil from celery obviating Sy

ngenta Method AG - 631B which is the current tolerance enforcement method for determining cy

prodinil in plant commodities . To further verify the suitability

of the method for analysis of cy

prodinil, a side - by- side comparison of the extraction solutions used in Methods AG - 597B (acetonitrile:water, 90:10, v/v) and AG - 631B (methanol:water, 80:20, v/v) was conducted to determine the relative performance of the two methods and to provide bridging data to support Method AG - 5 97B modified for L C/MS/MS. The ACN/water extraction provided acceptable recoveries (84.2 - 85.2%) of cy prodinil at the 0.05 and 25 ppm fortification levels. In addition, the ACN/water extraction procedure extracted more incurred residues of cy prodinil with less variability

than the methanol/water extraction procedure (i.e., 1.1 and 5.4% RSD for cy prodinil). For method AG - 631B , residues of cy prodinil were extracted with methanol:water (8:2, v/v), filtered, and acidified with dilute HCl. Residues were then cleaned - up by elution through a SPE column with ammoniated methanol. Residues were concentrated, reconstituted with 0.1% ammonium acetate , and analy zed by L C/MS/MS using a Phenomenex Sy nergi 4 micron Polar RP 80A column (75 x 2.00 mm) and a multi - compon ent mobile phase (Component A was 0.1% ammonium acetate in water and Component B was 90/10 acetonitrile:water plus 0.1% ammonium acetate) with gradient elution. The m/z 226.1 →93.1 ion transition was used for detection and quantitation of cy prodinil . Resi dues were quantified using external standards. The validated L OQ was 0.0 1 ppm for almond and pecan ; the L OD was not reported . For method AG 597B, residues of cy

prodinil were extracted with acetonitrile (ACN):water (90:10, v:v) by shaking at room temperature. An aliquot of each extract was centrifuged and filtered. An aliquot of the filtered extract was diluted 1:5 with 0.1% acetic acid in water and vortex mixed and then analy zed by L C/MS/MS.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 12 of 27 Both method s was validated in conjunction with the analysis of field trial samples. Control samples of peppers were fortified with cy prodinil at 0.0 1 - 2.1 ppm . Recoveries ranged from 71 - 112. Control samples of spinach were fortified with cy prodinil at 0.0 2 - 51 ppm . Recoveries ranged from 73 - 113. Control samples of lemon, lemon dried pulp, lemon juice, and lemon oil were fortified with cy

prodinil at 0.0 2 ppm , 0.01 - 2 ppm, 0.01 - 2.0 ppm, and 0.02 - 51 ppm, respectively . Recoveries ranged from 73 - 117 . Control samples of celery were fortified with cy prodinil at 0.0 5 - 0. 5 pp m . R ecoveries ranged from 85 - 10 7. Conclusions . Adequate HPLC/UV methods are available for enforcing the proposed new uses . All resi d ues of cy prodinil were determined using an adequate LC /MS/MS m ethod . The LC /MS/MS method L OQ for residues of cy prodini l in/on peppers, spinach, lemon, lemon dried pulp, lemon juice, lemon oil, and celery is 0.01, 0.02, 0.02, 0.01, 0.01, 0.02, and 0.0 5 ppm , respectively . **860.1360 Multiresidue Methods** Data are available depicting the recovery of cy prodinil and its metabol ite CGA - 232449 through FDA Multiresidue method testing protocols (C through E). Acceptable recoveries were obtained for cy prodinil in apple fortified at 0.50 ppm using Protocol D. These data were forwarded to FDA (G. Kram er, 11/28/1995 ). **860.1380 Storag e Stability**  DER 47161101 - 7, W. Cutchin,, 04/18/08) Peppers, spinach, lemon, lemon dried pulp, lemon juice, lemon oil, and celery samples were stored frozen ( - 20°C ± 10 °C ) for up to 9, 22. 3.5, 4.8, 5.6, 10.3, and 7.2 months before analysis , respectively . Demonstrated storage stability for the submitted field trial samples include 9 months for peppers, 5.8 months for dried lemon pulp, 5.9 months for lemon juice, and 10.6 months for lemon oil. T he stability of cy prodinil has been demonstrated in a variety of other crops, including mustard greens for 20 months and grape, wine, apple, wheat (ear and stalk), strawberry, and potato for up to 2 years (D233182, G. Kramer, 02/20/98; D288706, T. Bloem ,7/24/03) . Therefore, the submitted field trial data are suppo rted by acceptable storage stability data. **860.1400 Water, Fish, and Irrigated Crops** The proposed use s are not relevant to this guideline . **860.1460 Food Handling** The proposed use s are not relevant to this guideline.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 13 of 27 **860.1480 Meat, Milk, Poultry, and Eggs**  DP# s 345970 and 345182, W. Cutchin, 6/4/08 DP# 362484, J. Stokes, 9/15/09 DP# 378920, B. Cropp - Kohillig i an , 10/27/10 Adequate cattle feeding studies are available for cy prodinil , and tolerances for cy prodinil residues in livestock commodities were assessed in conjunction with petitions for tolerances on various plant commodities (DP#s 345970 , 345182 , and 378920 ) . Using the Agency ’s most recent guidance on constructing reasonably balanced livestock diets the maximum reasonably dietary burdens (M RDB s ) of livestock for c yp rodinil residues were calculated to be 0.8 8 ppm for beef cattle, 1.2 ppm for dairy c attle , and 0.0 05 ppm for poultry and swine . Based on these MDBs, tolerances for residues of cy prodinil and free and conjugated CGA - 304075, expressed in parent equivalents, were required on meat by products of cattle, goats, horses, and sheep at 0.02 ppm (L OQ). Based on the proposed modified use pattern of cy prodinil on almond and consequently a proposed increase in the established almond hull 8.0 ppm tolerance to 20 ppm, HED recalculated the dietary

burden using almond hull in place of wet apple pomace. The dietary contribution from the almond hulls alone did not increase the total dietary burden . However, this proposed amended use on almonds was wi thdrawn and the increased tolerance for almond hulls did not occur. C onclusions. The proposed new uses do not contain any livestock feed stuffs , therefore, HED has determined that the current ly established 0.0 2 ppm tolerance level s for meat by products of cattle, goats, horses, and sheep are adequate .Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 14 of 27 **860.1500 Crop Field Trials –**  **Peppers, Spinach, & Celery** MRID # s 48437401, 48437402, 48437403, & 48478501 The results from the field trials are summarized below . **TABLE 4 Summary of**  **Residue Data from Pepper Field and Greenhouse**  **Trials with**  **Cyprodinil.** Commodity Total App.

Rate (lb ai/A) [g a.i./ha] PHI

(days) Residue Level s (ppm) 1 n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Field Trials Bell Pepper 1.302 - 1.417

[1459.0 - 1588.3] 0 18 0.023 0.697 0.036 0.682 0.149 0.201 0.191 Nonbell Pepper 1.308 - 1.339

[1466.1 - 1500.8] 0 10 0.119 0.818 0.169 0.668 0.225 0.318 0.209 Greenhouse Trials Bell Pepper 1.304 - 1.315

[1461.6 - 1473.9] 0 8 0.04 0.32 0.08 0.2 7 0.21 0.20 0.09 Nonbell Pepper 1.327

[1487.4] 0 2 0.58 0.60 0.59 0.59 0.59 0.59 -- 1 n = no. of samples. 2 LAFT = lowest - average - field - trial; HAFT = highest - average - f ield - trial. **TABLE 5**  **Summary of Per Trial Average**  **Residue Data from Crop Field Tri**  **als with**  **Cyprodinil.** Commodity Total App.

Rate (lb ai/A) [g a.i./ha] PHI

(days) Residue Level s (ppm) 1 n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Spinach 1.300 - 1.367

[1457.1 - 1532.2] 0 22 4.58 36.9 5.64 32.1 10.3 11.8 7.36 1 Except f

or sample min/max, values reflect per trial averages; n = no. of samples. 2 LAFT = lowest - average - field - trial; HAFT = highest - average - f ield - trial. **TABLE 6**  **Summary of Per Trial Average**  **Residue Data from Crop Field Trials**  **with Cyprodinil.**  Commodity Tot al App.

Rate (lb ai/A) PHI

(days) Residue Level s (ppm) 1 n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Celery 2.16 - 2.23 0 8 3.2 17 3.5 17 8.5 8.7 4.5 1 Except for sample min/max, values reflect per trial averages; n = no. of field trial s. 2 LAFT = lowest - average - field - trial; HAFT = highest - average - f ield - trial. Followin g four foliar applications of the MAIproduct formulation at a total rate of 1.302 - 1.417 lb cy prodonil/A ( 1459.0 - 1588.3 g cy prodinil/ha), residues of cy prodinil (and per trial averages) in/on bell and nonbell peppers, respectively, at a 0 - day PHIwere 0.023 - 0.697 ppm and 0.119 - 0.818 ppm (0.036 - 0.682 ppm and 0.169 - 0.668 ppm) from the field trials and 0.04 - 0.32 ppm and 0.58 - 0.60 ppm (0.08 - 0.27 ppm and 0.59 ppm) from the greenhouse trials.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 15 of 27 Residue decline data show that cy prodinil decreases in field bell peppers and greenhouse bell peppers with increasing pre - harvest intervals. Residues of cy

prodinil (and per trial averages) were 4.58 - 36.9 ppm (5.64 - 32.1 ppm) in/on spina ch samples harvested 0 days following the last of four foliar broadcast applications of the MAIproduct formulation at a total seasonal rate of 1.300 - 1.367 lb cy prodonil/A (1457.1 - 1532.2 g cy prodinil/ha) . Residue decline data show that cy prodinil decrease s in spinach with increasing pre - harvest intervals. Residues of cy

prodinil (and per trial averages) were 3.2 - 17 ( 3.5 - 17 ) ppm in/on celery samples harvested 0 days following the last of four foliar broadcast applications of the WG MAIproduct formulation ( 37.5% cy

prodinil and 25% fludioxonil) at a total seasonal rate of 2.16 - 2.23 lb ai/A ( cy prodinil ) . Residue decline data show that cy prodinil decreases in celery with increasing pre - harvest intervals. Conclusion: The data adequately support the requested crop group tolerance and proposed use patterns. **860.1520 Processed Food and Feed** MRID #s 48437404 and 48437405 The results from the lemon processing study are summarized below . **Table 7**  **Residue Data from Lem**  **on Processing Study w**  **ith Cyprodinil**  **.** RAC Processed Commodity Total Rate (lb ai/A) PHI

(days) Residues (ppm) 1 Processing Factor2 Lemon Lemon (RAC) 0.336 0 0.185 0.214 **(0.200)** -- Dried Pulp 0.578 0.639 **(0.609)** 3x Juice <0.01 <0.01 **(<0.01)** <0.05x Oil 34.6 35.2 32. 5 **(34.1)** 171 x 1 LOQ (LLMV) was 0.01 ppm for lemon dried pulp and lemon juice, and 0.02 ppm for lemon oil. Average residues are **bolded** and reported in parenthesis. 2 Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the RAC]. Residues of cy

prodinil concentrated in dried lemon pulp and oil, but did not concentrate in lemon juice . Conclusion: The submitted lemon processing study is adequate. The tolerance for citrus oil can be decreased to 60 ppm (0.34 ppm x 171= 58 ppm).Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 16 of 27 **860.15 5**  **0 Harmonization with Codex**  There are currently

established Codex maximum residue limits (MRL s) for residues of cy prodinil in/on eggplant (0. 2 mg/kg) , peppers, sweet (0. 5 mg/kg), and tomato (0.5 mg/kg) . Neither Codex or Canada have MRLs for the leafy petioles crop group. Itis not possible to harmonize with Codex MRL s for residues of cy prodinil in/on eggplant, peppers, and tomato. Itis not possible to harmonize with Codex and Canadian MRL s for residues of cy

prodinil in/on these commodities because the US is recommending the establishment of a fruiting vegetable group 8 tolerance at 1. 5 ppm , and removal of the existing 0. 45 ppm tolerance in/on tomato and tomatillo, along with the 1.0 ppm tolerance on tomato paste . Canad a is proposing a fruiting vegetable crop group 8 - 10 MRLand an MRLfor the Vegetable, leafy, except brassica, subgroup 4A . **860.1650 Submittal of Analytical Reference Standards** Analy tical standard s for cy

prodinil ( expiration date 9/3 0/2012) and CGA - 304075 (expiration date 8/31/2012) are currently available in the EPA National Pesticide Standards Repository ( email communication with T. Cole , ACB, 09 /xx/201 1 ) . **860.1850/1900 Confined and Field Accumulation in Rotational Crops** DP# D2 57898, S. Levy, 2/8/2000 DP# D326346, W. Wassell, 10/18/2006 Adequate confined and limited field rotational crop studies are available and were conducted at 2.2x and 1.5x the current maximum use rate for rotated crops (1.3 lb ai/A). On the basis of these studies, the HED requested a field rotational crop study which also monitored for residues of CGA - 232449, NOA - 422054, CGA - 249287, and CGA - 263208. Inthe subsequent field accumulation study, cy prodinil (WDG) was applied to mustard greens at four test si tes in CA (2 tests) and NY (2 tests) as four broadcast foliar applications at 0.328 lb ai/A/application at 7 - day retreatment intervals for a total of 1.31 lb ai/A (1x rate). The primary mustard greens crop was destroyed and removed 7 days after the final application, and rotational crops of wheat, lettuce and garden beets were planted at PBI s of 27 to 32 days. Samples of lettuce, garden beet roots and tops, and wheat forage, hay, straw and grain were collected from each test at the appropriate stage of maturity . All samples were analy zed for residues of parent and each metabolite ( CGA - 232449, NOA - 422054, CGA - 249287, and CGA - 263208 ) using an adequate HPLC/MS method (Method 2213 - 01), which has a validated L OQ of 0.05 ppm for parent and each metabolite. A s residues of parent and each metabolite were <LOQ in/on all lettuce, garden beet and wheat RAC samples, HED concluded that rotational crop tolerances are not currently required.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 17 of 27 **860.1550 Proposed Tolerances** The Agency

has determined that the residue o f concern in plant commodities for the tolerance expression is only cy

prodinil . Tolerances have been established for residues of cy prodinil in/on a variety of crop commodities, at levels ran ging from 0.02 ppm in/on almond to 340 ppm in citrus oil [40 CFR §180.532(a)]. Tolerances have also been established at 0.02 ppm for cy prodinil and its metabolite CGA - 304075 residues in meat by products of cattle, goats, horses and sheep.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 18 of 27 **Table 8**  **. Tolerance Sum**  **ma ry for**  **Cyprodinil** Commodity Established/Proposed To lerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition **Tolerances Proposed Under PP# 1E**  **78 54**  Onion, bulb subgroup 3 - 07A 0.6 0.6 Onion, bulb, subgroup 3 - 07A Onion, bulb subgroup 3 - 07B 4.0 4.0 Onion, green, subgroup 3 - 07B Caneberry subgroup 13 - 07A 10.0 10 --- Bushberry subgroup 13 - 07B 3.0 3.0 --- Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit 2.0 2.0 Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F Low growing berry subgroup 13 - 07G, except c ranberry 5.0 5.0 Berry, low growing, subgroup 13 - 07G Vegetable, fruiting, group 8 - 10 1.3 1. 5 --- Vegetable, leafy, except Brassica, subgroup 04A 40 50 Vegetable, leafy, except b rassica, subgroup 4A Fruit, pome, group 11 - 10 1.7 1.7 --- Dragonfruit 2 .0 2 .0 Dragon fruit

**Tolerances That Need Amended Under PP#1E7854** Citrus, oil 100 ppm Section F 60 ppm NOF 60 --- **Tolerances That Need Remov**  **ed Under PP#1E7854** Onion, bulb 0.60 Onion, green 4.0 Caneberry subgroup 13A 10 Bushberry subgroup 13B 3.0 Grape 2.0 Straw berry 5.0 Tomato 0.45 **Tolerances Proposed**  **Under PP# 1E7869**  Leafy petioles subgroup 04B 30 30 Leaf petiole subgroup 4BCyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 19 of 27 **References** DP Numbers: 378920 Subject: Cyprodinil. Cyprodinil. Amended Use and Amended Tole rance Petition for Pome Fruit.

Summary of Analytical Chemistry and Residue Data. From: B. Cropp - Kohlligian To: L. Jones Dated: 10/27/10 MRID(s): 47644301 DP Numbers: 362486 Subject: Cyprodinil. Petition for Tolerance on Canola Seed Imported from Canada. Summary of

Analytical Chemistry and Residue Data. From: J. Stokes To: L. Jones Dated: 0 9/15/09 MRID(s): 47644301 DP Numbers: 345970 and 345182 Subject: Cyprodinil. Section 3 Requests for Uses on Tomato, Avocado, Herbs, Root Vegetables, Leave s of

Root and Tuber Vegetables, Lemon, Lime, Cucurbits, Kiwifruit, Green and Dry Bulb Onions, and Straw berries. Registrant’s Response to Conditional Registration on Carrots and Brassica Vegetables and Livestock Feeding Study. Summary of Analytical Chemis try and Residue Data. From: W. Cutchin To: W. Cutchin/B. Madden Dated: 0 6/ 0 4/08 MRID(s): 47161101 - 47161107 and 47169305 - 47169311 DP Number: 326346 Subject: Registration: 100 - 953; PP#8E05012; Cyprodinil on Onions. Review of Revised Label, Field Acc umulation in Rotational Crops, Storage Stability, and Analytical Methods Data Requested as Conditions of Registration. From: W. Wassell To: L. Jones/M. Waller Dated: 10/18/06 MRID(s): 46078901, 46078903, 46165901 DP Number: 288706, 288708, 288710, and 288 773 Subject: Cyprodinil (PC Code 288202). Section 3 Registration for Application of Cyprodinil to Lychee,

Longan, Spanish Lime, Rambutan, and Pulasan (ID# - 2E06447); Brassica Leafy Greens Crop Subgroup, Head and Stem Brassica Crop Subgroup, and Turnip Greens (ID# - 2E06485); Carrot (ID# - 2E06461); and Herb Crop Subgroup (ID# - 3E06529). Summary of Residue Chemistry Data. From: T. Bloem To: R. Forrest Dated: 0 7/24/03 MRID(s): 45682401, 45721502, 45726101, 45726102, 45795301, 45795302, and 45839801 DP Number: 257898 Subject: PP# 8E05012. Cy prodinil in/on Straw

berries and Bulb Vegetables (Crop Group 3). Evaluation of Residue Data and Analytical Methods. From: S. Levy To: R. Forrest/S. Brothers Dated: 0 2/ 0 8/00 MRID(s): 44615602, 44615601, 44867312, 44867314Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 20 of 27 DP Numbers: 243198 Subject: Cyprodinil. HED Metabolism Assessment Review Committee Meeting of 0 2/10/98. From: G. Kramer To: HED MARC Members Dated: 0 3/11/98 MRID(s): None DP Numbers: 233561, 233562, 233928, 233182, 239674, and 236086 Subject: P P# 6F04656. New Chemical - Cyprodinil (i.e., Vangard®) in/on Stone Fruit, Pome Fruit, Almonds and Grapes. Evaluation of Residue Data and Analytical Methods. From: G. Kramer To: M. Waller/T. Ellwanger Dated: 0 2/20/98 MRID(s): 44186401, 44186404 and 4418641 0 thru 44186420; 43908402, 43908403 and 43908438 thru

43908445; 44382601; and 44275401 and 44275402 DP Number: 219794 Subject: PP#s 5G04553. New Chemical

– Cyprodinil and Propiconazole in or on Stone Fruit. Evaluation of Residue Data and Analytical Meth ods. From: G. Kramer To: C. Welch/ K. Whitby Dated: 0 2/13/96 MRID(s): 43709001 through 43709004, 43709048 through 43709055, and 43737603 DP Number: None Subject: Multiresidue Method Testing Data for Cyprodinil and CGA - 232449 From: G. Kramer To: B. McMahon , FDA Dated: 11/28/95 MRID(s): 43709050 Attachments: Appendix I - Inte rnational Tolerances Appendix II

– Tolerance Assessment Calculations **F. DOCUMENT TRACKING**  RDI: SHummel 0 5 / 3 /1 2 Petition Number: 1E 7 8 54 & 1E7869 DP#: 389554 & 391680 PC Code: 288202 Template Version September 2005Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 21 of 27 **Appendix I. International Tolerances**  **Cyprodinil** (PC Code 288202; 0 3 / 06 /1 2 ) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 40 CFR 180.532: Plant/Livestock: Sum of cy prodinil 4 - cyclopropyl - 6 - methyl -N -phenyl - 2 - py rimidinamine and free and conjugated CGA - 304075 4 - (4 - cyclopropyl - 6 - methyl -py

rimidin - 2 - yl amino) -phenol, calculated as the stoichiometric equivalent of cy prodinil. 4 - cyc lopropyl - 6 -

methyl - N -phenyl - 2 - py rimidinamine Cy prodinil The residue is fat soluble.

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Onion, bulb subgroup 3 - 07A 0.60 0.3 onion, bulb Onion, green subgroup 3 - 07B 4.0 4.0 green onions Caneberry subgroup 13 - 07A 10 6.2 blackberries, loganberries, raspberries 0.5 raspberries, red, black Bushberry subgroup 13 - 07B 3.0 2.0 blueberries, currants, elderberries, gooseberries, huckleberries, lingonberries, salal berries, saskatoon berries (juneberries) Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit 2.0 2.0 gooseberries, grape 3.0 raisins 3 grapes 5 dried grapes (=currants, raisins and sultanas) Low growing berry subgroup 13 - 07G, except cranberry 5. 0 2.0 blueberries, lingonberries 3.5 straw berries 2 straw berry Dragon fruit 2.0 Fruit, pome, group 11 - 10 1.7 0.1 pome fruit 0.05 apple 1 pear Vegetable, fruiting, group 8 - 10 1. 5 0.2 eggplant 0.5 Peppers, sweet (including pimento or pimiento) , tomatoCyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 22 of 27 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex Vegetable, leafy, except brassica, subgroup 04A

50 30 amaranth, arugula, corn salad, dandelion leaves, dock, edible leaved chrysanthemum, endives, fresh chervil leaves, fresh parsley leaves, garden cress, garden purslane , garland chrysanthemum, head lettuce, leaf lettuce, orach leaves, radicchio, upland cress, winter purslane 10 lettuce, head, le ttuce, leaf

Citrus oil 60 Leafy petioles subgroup 04B 30 Completed: M. Negussie; 03/08/12 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant. 2 Mexico a dopts US tolerances and/or Codex MRLs for its export purposes.Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 23 of 27 **Appendix II**  **. Tolerance Assessment Calculations.** For each of the crops listed below, the OECD MRL Calculator User Guide (SOP), along with the tolerance spreadsheet, wa s used for calculating recommended tolerances. As specified in the SOP, the tolerance calculation is in the region of the 95 th percentile of the underlying residue distribution, and is more likely to overestimate rather than underestimate the 95 th percentile. The rounding procedures specified in the SOP were also used. The OECD tolerance spreadsheet does not require the use of maximum - likelihood estimation (MLE) procedures for values <LOQ. Using the OECD MRLCalculator , the recommended tolerances are 50 ppm for spinach, 1.0 ppm for peppers and 3 0 ppm for celery .Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 24 of 27 **Cyprodinil Spinach**  **US/PMRA 0 day PHI**  **Total number of data (n)** 11 **Percentage of censored data** 0% **Number of non -**  **censored data** 11 **Lowest residue** 5.640 **Highes t residue**  32.100 **Median residue** 10.700 **Mean** 11.773 **Standard deviation (SD)** 7.319 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  32.100

**- Mean + 4 SD**  41.050

**- CF x 3 Mean**  35.318 **Unrounded MRL** 41.050 **Rounded MRL 50** 

**Residues (mg/kg) n**  5.64 1 6.08 1 6.59 1 8.26 1 9.63 1 10.7 1 11.4 1 11.9 1 13 1 14.2 1 32.1 1Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 25 of 27 **Cyprodinil Bell Pepper**  **US 0**  **- day PHI**  **Total number of data (n)** 13 **Percentage of censored data** 0% **Num ber of non**  **- censored data**  13 **Lowest residue** 0.036 **Highest residue** 0.682 **Median residue** 0.189 **Mean** 0.200 **Standard deviation (SD)** 0.165 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.682

**- Mean + 4 SD**  0.860

**- CF x 3 Mean**  0.601 **Unrounded MRL** 0.860 **Rounded MRL 0.9** 

**Residues (mg/kg) n**  0.0358 1 0.0383 1 0.08 1 0.1 1 0.134 1 0.152 1 0.189 1 0.21 1 0.23 1 0.234 1 0.248 1 0.27 1 0.682 1Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 26 of 27 **Cyprodinil Non**  **- bell Pepper**  **US 0**  **- day PHI**  **Total number of data (n)** 6 **Percentage of censored data** 0% **Number of non -**  **censored data** 6 **Lowest residue** 0.169 **Highest residue** 0.668 **Median residue** 0.275 **Mean** 0.363 **Standard deviation (SD)** 0.211 **Correction factor for censoring (CF)** 1.0 00 **Proposed MRL estimate**

**- Highest residue**  0.668

**- Mean + 4 SD**  1.209

**- CF x 3 Mean**  1.090 **Unrounded MRL** 1.209 **Rounded MRL 1.5**  High uncertainty of MRL estimate. [Small dataset] **Residues (mg/kg) n**  0.169 1 0.202 1 0.273 1 0.277 1 0.59 1 0.668 1Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 3 89554 & D391680

Page 27 of 27 **Cyprodinil Leafy Petioles**  **- Celery** 

**US 0 day PHI**  **Total number of data (n)** 8 **Percentage of censored data** 0% **Number of non -**  **censored data** 8 **Lowest residue** 3.500 **Highest residue** 16.500 **Median residue** 8.450 **Me an**  8.656 **Standard deviation (SD)** 4.472 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  16.500

**- Mean + 4 SD**  26.544

**- CF x 3 Mean**  25.969 **Unrounded MRL** 26.544 **Rounded MRL 30** 

**Residues (mg/kg)**  **n** 3.5 1 3.6 1 5.95 1 7.2 1 9.7 1 10.8 1 12 1 16.5 1