Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

MEMORANDUM

Date: July 1, 2015

SUBJECT: Cyprodinil. Expansions of Existing Crop Group/Representative Commodity

Uses to Stone Fruit Group 12-12, and Adding New Uses on the Artichoke, Guava, 

Pomegranate, Passionfruit, Feijoa,Jaboticaba, Wax Jambu, Starfuit, and Acerola

and Amended Uses on Greenhouse Cucumbers and Small Tomatoes. Summary 

of Analytical Chemistry and Residue Data.

PC Code: 288202 DP Barcode: D421157

Decision No.: 490951 Registration Nos.: 100-828, 100-953 and 100-1317

Petition No.: 4E8273 Regulatory Action: Section 3

Risk Assessment Type: NA Case No.: 7025

TXR No.: NA CAS No.: 121552-61-2

MRID No.: 49346901 – 05 40 CFR: 180.532

 

FROM: Thurston G. Morton, Chemist

Risk Assessment Branch 4

Health Effects Division (7509P)

THROUGH: Charles Smith, Acting Branch Chief

Risk Assessment Branch 4

Health Effects Division (7509P)

And

Sheila Piper,Senior Chemist

RAB6/HED, 7509P, Chemistry Science Advisory Council (ChemSAC)

Sumitra Bose Biswas, Chemist

RAB6/HED, 7509P, ChemSAC

TO: Laura Nollen/Barbara Madden, RM20

Minor Use & Emergency Response Branch

Registration Division (7505P)
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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Executive Summary

Cyprodinil is an anilino-pyrimidine fungicide used to control various plant diseases on a wide 

variety of fruit, nut, vegetable and herb crops. Under PP#4E8273, Interregional Research Project 

No. 4 (hereafter referred to as IR-4), on behalf of the Agricultural Experiment Stations, is 

requesting the establishment of tolerances for residues of cyprodinil [4-cyclopropyl-6-methyl-Nphenyl-2-pyrimidinamin] in/on the following raw agricultural commodities:

Artichoke..... ............................................................................4.0 ppm

Guava........................................................................................1.5 ppm

Passionfruit.............................................................1.5 ppm

Feijoa....................................................................1.5 ppm

Jaboticaba...............................................................1.5 ppm

Wax Jambu.............................................................1.5 ppm

Starfruit ....................................................................................1.5 ppm

Acerola......................................................................................1.5 ppm

Pomegranate..............................................................................7.0 ppm

Fruit, stone, group 12-12......................................................2.0 ppm

In addition, IR-4 is requesting the removal of the currently established tolerance for residues of 

cyprodinil in/on Fruit, stone, group 12 (2.0 ppm) once the fruit, stone, group 12-12 is established.

In conjunction with PP#4E8273, IR-4 is requesting a Section 3 registration for VanguardTM WG 

(EPA Reg. No. 100-828), a 75% water dispersible granule (WDG) formulation for use on 

artichoke, acerola, feijoa, guava, jaboticaba, passionfruit, starfruit, and wax jambu; Switch® 62.5 

WG Fungicide (EPA Reg. No. 100-953), a 37.5% water dispersible granule (WDG) formulation 

of cyprodinil for use on guava, passionfruit, starfruit, and pomegranate (post-harvest); and Inspire 

Super TM Fungicide (EPA Reg. No. 100-1317), a 2.09 lb ai/gallon emulsion oil in water (EW) 

formulation to artichoke. In support of these new uses, IR-4 has submitted new magnitude of the 

residue data for cyprodinil using the WDG formulation of cyprodinil at the proposed use rate.

In addition, IR-4 is requesting amendments for the Section 3 registrations for VanguardTM WG 

(EPA Reg. No. 100-828) and Inspire Super TM Fungicide (EPA Reg. No. 100-1317) to expand 

currently registered foliar uses for stone fruit group 12 to include the additional commodities 

specified under the following new crop group: Fruit, stone, group 12-12. 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 wishes to rely on previously submitted 

residue chemistry data which support the currently registered uses of cyprodinil.

In addition, IR-4 is proposing to remove the restriction against using VanguardTM WG (EPA Reg. 

No. 100-828) and Switch® 62.5 WG Fungicide (EPA Reg. No. 100-953) on small tomatoes 

along with removing the restriction against using Inspire Super TM Fungicide (EPA Reg. No. 100-

1317) on greenhouse cucumbers. IR-4 has submitted new greenhouse grown cucumber 

magnitude of the residue data to demonstrate that the existing tolerance for residues of cyprodinil 

in/on vegetable, cucurbit, group 9 (0.70 ppm) is adequate for the proposed use. IR-4 has also 

submitted new small tomato magnitude of the residue data to demonstrate the existing tolerance 
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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for residues of cyprodinil in/on vegetable, fruiting, group 8-10 (1.5 ppm) is adequate for the 

proposed use.

One of the products (EPA Reg. No. 100-1317) addressed herein contains a second active 

ingredient (difenoconazole) and another product (EPA Reg. No. 100-953) also contains a 

second active (fludioxonil). Difenoconazole and fludioxonil are addressed under separate 

reviews. The subject review addresses the proposed uses and supporting data for 

cyprodinil only. 

The nature of cyprodinil residues in plants is understood based on adequate metabolism studies 

on apple, peach, potato, tomato, and wheat. Only residues of parent cyprodinil need to be 

included in the tolerance expression and considered for risk assessment for plant commodities.

The nature of cyprodinil residues in ruminants is also understood based on an adequate goat 

metabolism study. The residues of concern in ruminants are cyprodinil and its hydroxylated 

metabolite CGA-304075 (free and conjugated). No poultry metabolism study is available, but 

HED has concluded that none is required. There are no new livestock feed stuffs associated with 

the proposed new uses of cyprodinil.

Adequate HPLC/UV methods (Methods AG-631 and AG-631B) are available for enforcing 

tolerances of cyprodinil in/on plant commodities. The limits of quantitation (LOQ) for the plant

methods range from 0.01 to 0.065 ppm depending on the commodity. An adequate LC/MS 

method (GRM010.01A) is also available for enforcing tolerances of cyprodinil residues in

livestock commodities. The method LOQ for this method is 0.02 ppm for the combined residues 

of cyprodinil and its metabolite CGA-304075 (free and conjugated), expressed as parent. 

In the submitted field trial study, residues of cyprodinil 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 HPLC/UV Syngenta Method AG-631B, “Analytical Method for the 

Determination of Residues of CGA-219417 in Crops by High Performance Liquid 

Chromatography with Column Switching.” Syngenta Methods AG-631 and AG-631B are the 

current tolerance enforcement methods for determining cyprodinil in plant commodities. 

Cucumber, globe artichoke, guava, pomegranate, and tomato samples were stored frozen (-20°C 

± 10°C) for up to 12, 2, 22, 11, and 10 months before analysis, respectively. The stability of 

cyprodinil 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. 

Therefore, the submitted field trial data are supported by acceptable storage stability data. 

Data are adequate to support the proposed uses of cyprodinil. The HAFT residue level of 

cyprodinil in greenhouse cucumber, globe artichoke, guava, and small greenhouse tomato

resulting from four applications for a seasonal rate of 1.3 lb cyprodinil a.i./A was 0.58, 1.33, 

0.522, and 1.12 ppm, respectively. Maximum residue levels of cyprodinil were 0.62 ppm in 

greenhouse cucumber, 1.52 ppm in globe artichoke, 0.626 ppm in guava, and 1.28 ppm in small 

greenhouse tomato. The HAFT residue level and maximum residue level of cyprodinil resulting 

from post-harvest treatment of pomegranate were 3.42 and 3.60 ppm, respectively. There are an 

adequate number of field trials from representative geographical locations. 
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The Organization for Economic Cooperation and Development (OECD) tolerance calculation 

procedures were used to determine appropriate tolerance levels. A tolerance level of 10 ppm for 

pomegranate, 4.0 ppm for globe artichoke, and 1.5 ppm for guava is appropriate. The 1.5 ppm 

tolerance for guava was translated to acerola, feijoa, jaboticaba, passionfruit, starfruit, and wax 

jambu, in accordance with “Reviewer’s Guide and Summary of HED ChemSAC Approvals for 

Amending Crop Group/Subgroups [40 CFR 180.41] and Commodity Definitions [40 CFR 

180.1(h)]” (B. Schneider, 6/14/06). Note that the recommended tolerance level for 

pomegranate is different than that petitioned-for by the registrant due to the decision that 

each of the post-harvest scenarios/techniques represented by the data constitutes separate 

datasets for tolerance determination with the OECD tolerance calculation procedures.

No Codex MRLs are established in/on globe artichoke, acerola, feijoa, guava, jaboticaba, 

passionfruit, starfruit, wax jambu, and pomegranate. Canadian and Mexican MRLs has not been 

established for the requested crops. The Agency will be harmonized with Codex on the fruit, 

stone, group 12-12 MRL of 2.0 ppm. 

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for cyprodinil. With regards to cyprodinil for 

PP#4E8273, pending submission of a revised Section B (see requirements under Directions for 

Use) and a revised Section F (see requirements under 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 WG Fungicide (EPA Reg. No. 100-953), and Inspire Super TM

Fungicide (EPA Reg. No. 100-1317) to expand currently registered foliar uses for globe 

artichoke, acerola, feijoa, guava, jaboticaba, passionfruit, starfruit, wax jambu, and pomegranate; 

along with the expansion of fruit, stone, group 12-12 or establishment of tolerances for residues 

of cyprodinil only in/on the following commodities:

Artichoke, globe.......................................................................4.0 ppm

Guava........................................................................................1.5 ppm

Passionfruit.............................................................1.5 ppm

Feijoa....................................................................1.5 ppm 

Jaboticaba...............................................................1.5 ppm 

Wax Jambu.............................................................1.5 ppm

Starfruit ....................................................................................1.5 ppm

Acerola......................................................................................1.5 ppm

Pomegranate............................................................10 ppm

Fruit, stone, group 12-12......................................................2.0 ppm

In addition, the restriction on use of Switch® 62.5 WG Fungicide (EPA Reg. No. 100-953) and 

VanguardTM WG (EPA Reg. No. 100-828) on small size tomato may be removed. The restriction

on use of Inspire Super TM Fungicide (EPA Reg. No. 100-1317) on greenhouse cucurbits may also 

be removed.

The approved amended registrations for VanguardTM WG (EPA Reg. No. 100-828), Switch® 

62.5 WG Fungicide (EPA Reg. No. 100-953), and Inspire Super TM Fungicide (EPA Reg. No. 
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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100-1317) are limited to expansions to add the commodities specified under the new crop 

groups/subgroups and do not include substantive changes to currently registered use patterns 

(i.e., maximum use rates, retreatment intervals, preharvest intervals, use of adjuvants, etc.). 

A human health risk assessment is forthcoming.

860.1200 Directions for Use – Pertains to Cyprodinil Only

Section B of petition 4E8273 pertaining to uses on artichoke should be revised to specify globe

artichoke only. [Note: IR-4 submitted draft supplemental labels which are substantially similar 

to Section B of the petition and should be amended as well.] 

860.1550 Proposed Tolerances

Section F of petition 4E8273 must be revised as follows. The recommended tolerance for 

residues of cyprodinil in/on pomegranate (10 ppm) is not the same as the petitioned-for tolerance 

(7.0 ppm) due to the decision that data reflecting each of the three post-harvest 

scenarios/techniques constitute separate datasets for tolerance determination with the OECD 

tolerance calculation procedures. In addition the commodity definition should be for 

Artichoke, globe.

Background

Cyprodinil is an anilino-pyrimidine fungicide used to control various plant diseases on a wide 

variety of fruit, nut, vegetable and herb crops. Tolerances for residues of cyprodinil have been 

established in/on a variety of crop commodities at levels ranging from 0.02-170 ppm [40 CFR 

§180.532]. Tolerances have also been established at 0.02 ppm for cyprodinil residues in meat 

byproducts of cattle, goats, horses, and sheep. No tolerance is established for poultry byproducts. 

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

cyprodinil are presented in Tables 1 and 2.

Table 1. Cyprodinil Nomenclature.

Compound

N

N

CH3

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-phenylCAS 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% cyprodinil
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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Table 2. Physicochemical Properties of Technical Grade of Cyprodinil.

Parameter Value Reference

Melting point/range 75.9 0C DP#s 345970 and 345182, W. 

Cutchin, 6/4/08 pH 9.5 at 25 0C (1% aqueous dispersion)

Density 1.21 g/cm3at 20 0C

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 0C

Dissociation constant, pKa 4.44 at 20 0C

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#: 421157

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860.1200 Directions for Use

Table 3. Summary of Proposed Directions for Use of Cyprodinil

Applic. Timing, 

Type, and 

Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

per Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Artichoke1

Broadcast foliar

Ground/Aerial/

Chemigation

Vangard WG

75% WDG

[100-828]

0.33 4 implied 1.3 3

A minimum retreatment 

interval (RTI) of 14 days 

is proposed. 

Broadcast foliar

Ground Only

Inspire Super

2.09 lb/gal 

EW

[100-1317]

0.33 4 implied 1.3 3

A minimum retreatment 

interval (RTI) of 7-10 

days is proposed.

Acerola, feijoa, guava, jaboticaba, passionfruit, starfruit, wax jambu

Broadcast foliar

Ground/Aerial/

Chemigation

Vangard WG

75% WDG

[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% WDG

[100-953]

0.33 1 by aerial

4 implied 1.3 0

A minimum retreatment 

interval (RTI) of 7-10 

days is proposed. Aerial 

application in California 

only.

Pomegranate (Post-harvest dip/drench)

In-Line 

Dip/Drench

Switch 

62.5WG

37.5% WDG

[100-953]

0.45 lb

ai/100 gal 

of water, 

wax/emul

sion, or 

aqueous 

dilution of 

wax/oil 

emulsion

1-2

0.45-0.90 lb 

ai/100 gal of 

water, 

wax/emulsion, 

or aqueous 

dilution of 

wax/oil 

emulsion

0

For maximum decay 

control, treat fruit once 

before storage and once 

after storage, prior to 

marketing.

Green House Grown Cucumbers

Broadcast foliar

Ground Only

Inspire Super

2.09 lb/gal 

EW

[100-1317]

0.0075 lb 

ai/1000 ft2 NS NS 7

A minimum retreatment 

interval (RTI) of 7-10 

days is proposed.

1 Although not specified in the use directions, the use on artichoke is intended to be for globe artichoke consistent 

with the supporting data.

Conclusions. The proposed use directions are sufficient to allow for evaluation of the available 

residue data. 
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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860.1300 Nature of the Residue - Plants

DP# 219794, G. Kramer, 2/13/96

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 cyprodinil is 

metabolized primarily by hydroxylation followed by sugar conjugation. Cleavage of the amino 

bridge, opening of the pyrimidine ring, opening of the cyclopropyl ring and formation of 

thiolactic acid conjugates 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 cyprodinil. 

860.1300 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 understood based on acceptable lactating 

goat metabolism studies using [14C-phenyl] and [14C-pyrimidinyl] cyprodinil. The metabolism of 

cyprodinil in ruminants proceed predominantly via hydroxylation followed by conjugation with 

sulfuric and glucuronic acid. Breakdown of the pyrimidinyl ring was seen only in the liver and 

resulted in Metabolite L1. Cleavage of the amino bridge between the phenyl and the pyrimidinyl 

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 [14C-pyrimidinyl]cyprodinil.

HED originally concluded there were no cyprodinil metabolites of toxicological or regulatory

concern in ruminant milk and tissues based on the dietary burden associated with the registered 

cyprodinil 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 cyprodinil feeding study would be required in which residues of 

cyprodinil 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 cyprodinil and metabolite CGA-304075 (free and 

conjugated), expressed in parent equivalents.

A poultry metabolism for cyprodinil has not been submitted and none has been requested since 

the potential dietary exposure of poultry to cyprodinil residues is extremely low (estimated at 

0.005 ppm based on canola meal consumption). There is no reasonable expectation of finite 

residues in poultry and egg. However, if future crops are added that substantially increase the 

poultry dietary burden, then HED may require a study.
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression

for Cyprodinil

Matrix Risk Assessment Tolerance Expression

Plants cyprodinil cyprodinil

Livestock cyprodinil and CGA-304075 cyprodinil and CGA-304075

Water cyprodinil and CGA 249287 NA

860.1340 Residue Analytical Methods

Enforcement methods. Adequate HPLC/UV methods with column switching (Syngenta Methods 

AG-631 and AG-631B) are available for enforcing tolerances of cyprodinil on plant 

commodities. The LOQs for these methods range from 0.01 to 0.065 ppm depending on the 

plant commodities. Method AG-631B also contains procedures for confirmatory analysis by

GC/NPD.

An adequate HPLC/MS method (GRM010.01A) is also available for enforcing tolerances in 

livestock commodities. This method determines residues of both parent and the metabolite 

CGA-304075 (free and conjugated), expressed as parent. The LOQ is 0.01 ppm for each analyte 

for a combined LOQ of 0.02 ppm.

Data collection methods. In the submitted field trial studies, residues of cyprodinil 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 HPLC/UV Syngenta Method AG631B, “Analytical Method for the Determination of Residues of CGA-219417 in Crops by High 

Performance Liquid Chromatography with Column Switching.” Syngenta Methods AG-631 and 

AG-631B are the current tolerance enforcement methods for determining cyprodinil in plant 

commodities

For method AG-631B, residues of cyprodinil 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 analyzed by LC/MS/MS using a Phenomenex Synergi 4 micron PolarRP 80A column (75 x 2.00 mm) and a multi-component 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 cyprodinil. Residues were quantified using external standards. The 

validated LOQ was 0.01 ppm; the LOD was not reported.

The method was validated in conjunction with the analysis of field trial samples. Control 

samples of were fortified with cyprodinil at 0.01-2.1 ppm. Recoveries ranged from 70-109%. 

Control samples were fortified with cyprodinil at 0.02-10 ppm. Recoveries ranged from 68-

112%. 

Conclusions. Adequate HPLC/UV methods are available for enforcing the proposed new uses. 

All residues of cyprodinil were determined using an adequate HPLC/UV or LC/MS/MS method. 
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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860.1360 Multiresidue Methods

G. Kramer, 11/28/1995

Data are available depicting the recovery of cyprodinil and its metabolite CGA-232449 through 

FDA Multiresidue method testing protocols (C through E). Acceptable recoveries were obtained 

for cyprodinil in apple fortified at 0.50 ppm using Protocol D. These data were forwarded to 

FDA.

860.1380 Storage Stability

D233182, G. Kramer, 02/20/98

D288706, T. Bloem ,7/24/03

Cucumber, globe artichoke, guava, pomegranate, and tomato samples were stored frozen (-20°C 

± 10°C) for up to 12, 2, 22, 10, and 11 months before analysis, respectively. The stability of 

cyprodinil 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. 

Therefore, the submitted field trial data are supported by acceptable storage stability data. 

860.1400 Water, Fish, and Irrigated Crops

The proposed uses are not relevant to this guideline.

860.1460 Food Handling

The proposed uses are not relevant to this guideline.

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-Kohilligian, 10/27/10

Adequate cattle feeding studies are available for cyprodinil, and tolerances for cyprodinil

residues in livestock commodities were assessed in conjunction with petitions for tolerances on 

various plant commodities. Using the Agency’s most recent guidance on constructing reasonably

balanced livestock diets the maximum reasonably dietary burdens (MRDBs) of livestock for 

cyprodinil residues were calculated to be 0.88 ppm for beef cattle, 1.2 ppm for dairy cattle, and 

0.005 ppm for poultry and swine. Based on these MDBs, tolerances for residues of cyprodinil 

and free and conjugated CGA-304075, expressed in parent equivalents, were required on meat 

byproducts of cattle, goats, horses, and sheep at 0.02 ppm (LOQ). 

Previously, 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 withdrawn and the increased tolerance for 

almond hulls did not occur.

Conclusions. The proposed new uses do not contain any livestock feed stuffs, therefore, HED 

has determined that the currently established 0.02 ppm tolerance levels for meat byproducts of 

cattle, goats, horses, and sheep are adequate.
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860.1500 Crop Field Trials

MRID #s 49346901, 49346902, 49346903, 49346904, & 49346905

DP# 354013, 3/20/09, B. Cropp-Kohlligian

The results from the field trials are summarized below.

Cucumber (Greenhouse) Small and Large Varieties

Following four applications of a 2.09 lb ai/gal EW formulation at a total application rate of 1.30–

1.33 lbs ai/A, individual sample (and per-trial average) residues of cyprodinil were 0.08–0.62 

ppm (0.11–0.58 ppm) in/on cucumber fruit collected at a PHI of 0 days. There were no 

significant differences between the residues in the large variety cucumbers vs. the small variety

cucumbers. 

Table 4. Summary of Residues from Cucumber (Greenhouse) Field Trials with EW Formulation of 

Cyprodinil.

Crop Matrix

Total 

Application Rate

(lb ai/A)

PHI 

(days) n

1

Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median3 Mean3SD3

Cyprodinil

Cucumber (Large 

and Small), fruit 1.3030–1.3276 0 5 0.08 0.62 0.11 0.58 0.34 0.32 0.20

1

 n = number of field trials.

2 Values based on total number of samples.

3 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at 

the LOQ. The LOQ was 0.015 ppm for cyprodinil in all matrices.

Artichoke, globe

Following four or five applications of a 2.09 lb ai/gal EW formulation at a total application rate 

of 1.300–1.655 lbs ai/A, individual sample (and per-trial average) residues of cyprodinil were 

0.825–1.52 ppm (0.932–1.33 ppm) in/on mature globe artichoke flower buds collected at a PHI

of 3 days. There were no significant differences between the residues in the perennial globe 

artichokes vs. the annual globe artichokes. 

Table 5. Summary of Residues from Globe Artichoke Field Trials with EW Formulation of Cyprodinil.

Crop Matrix

Total 

Application Rate

(lb ai/A) 4

PHI 

(days) n

1

Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median3 Mean3SD3

Cyprodinil

Globe artichoke, 

mature flower 

buds

1.300–1.655 3 4 0.825 1.52 0.932 1.33 1.22 1.17 0.18

1

 n = number of field trials.

2 Values based on total number of samples.

3 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at 

the LOQ. The LOQ was 0.01 ppm for cyprodinil in all matrices.

4 Calculated by the reviewer.

Side-by-side field trial data on lettuce, mustard greens and tomatoes comparing residues of 

cyprodinil resulting from multiple late season uses of the EW formulation with a WDG 

formulation of cyprodinil are available (DP# 354013, 3/20/09, B. Cropp-Kohlligian). Cyprodinil 

residues were similar for the EW and WDG formulations on all three crops. 
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 12 of 21

Guava

Following four applications of Switch 62.5WG at a total application rate of 1.31–1.43 lbs ai/A, 

individual sample (and per-trial average) residues of cyprodinil were 0.345–0.626 ppm (0.353–

0.522 ppm) in/on guava fruit collected at a PHI of 0 days. 

Table 6. Summary of Residues from Guava Field Trials with WDG Formulation of Cyprodinil.

Crop Matrix

Total 

Application Rate

(lb ai/A) 4

PHI 

(days) n

1

Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median3 Mean3SD3

Cyprodinil

Guava fruit 1.31–1.43 0 4 0.345 0.626 0.360 0.522 0.487 0.464 0.07

1

 n = number of independent field trials.

2 Values based on total number of samples.

3 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at 

the LOQ. The LOQ was 0.01 ppm for cyprodinil in all matrices.

4 Calculated by the reviewer.

Pomegranate (Post-Harvest)

Data reflect three different post-harvest treatment scenarios/techniques of 1 or 2 applications 

using a water dispersible granule (WDG) formulation of cyprodinil (Switch 62.5WGTM). Each of 

these post-harvest scenarios/techniques are considered separate/discrete datasets for tolerance 

determination. Following one application as a dip with wax at 0.45 lb ai/100 gal, individual 

sample (and per-trial average) residues of cyprodinil were 0.24-1.60 ppm (0.93-1.52 ppm) in/on 

pomegranate collected on the day of treatment. Following a total of two applications, one 

application as a dip with wax at 0.45 lb ai/100 gal and a second application as a dip with no wax 

at 0.45-0.46 lb ai/100 gal, individual sample (and per-trial average) residues of cyprodinil were 

2.22-3.60 ppm (2.56-3.42 ppm) in/on pomegranate treated and collected on the same day. 

Following a total of two applications, one application as a dip with wax at 0.45-0.46 lb ai/100 gal 

and then a drench application with no wax at 0.45-0.46 lb ai/100 gal, individual sample (and pertrial average) residues of cyprodinil were 0.38-2.69 ppm (0.53-2.25 ppm) in/on pomegranate 

treated and collected on the same day. 

Table 7. Summary of Residues from Pomegranate Post-Harvest Trials with WDG Formulation of Cyprodinil.

Crop Matrix

Total Application 

Rate

(oz ai/100gal)

1

/

[lb ai/100 gal]1

PHI 

(days) n

2

Residues (ppm)

Min.3 Max.3 LAFT4 HAFT4 Median4 Mean4SD4

Cyprodinil

Pomegranate 7.2 / [0.45] 50 4 0.24 1.60 0.93 1.52 1.155 1.02 0.576

Pomegranate 14.4-14.6 / [0.9] 60 4 2.22 3.60 2.56 3.42 3.260 3.13 0.384

Pomegranate 14.4-14.6 / [0.9] 70 4 0.38 2.69 0.53 2.25 1.845 1.55 0.893

1 Calculated by the reviewer.

2

 n = number of independent trials.

3 Values based on total number of samples.

4 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at 

the LOQ. The LOQ was 0.01 ppm for cyprodinil in all matrices.

5 One application as a dip with wax.

6 Total of two applications. One application as a dip with wax (0.45-0.46 lb ai/100 gal) and a second application as a dip with 

no wax (0.45-0.46 lb ai/100 gal). Applications were allowed to dry before the second application was applied. Samples were 

treated and collected on the same day.

7

 Total of two applications. One application as a dip with wax (0.45-0.46 lb ai/100 gal) and then a drench application with no 

wax (0.45-0.46 lb ai/100 gal). Applications were allowed to dry before the second application was applied. Samples were 

treated and collected on the same day.
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 13 of 21

Tomato (Greenhouse) Small Varieties

Following four applications of a 37.5% water dispersible granule (WDG) formulation at a total 

application rate of 1.31-1.33 lb ai/A, individual sample (and per-trial average) residues of 

cyprodinil were 0.278–1.28 ppm (0.317–1.12 ppm) in/on tomato fruit collected at a PHI of 0 

days. 

Table 8. Summary of Residues from Tomato (Greenhouse) Small Variety Field Trials with WDG 

Formulation of Cyprodinil.

Crop Matrix

Total 

Application Rate

(lb ai/A)

4

PHI 

(days) n

1

Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median3 Mean3SD3

Cyprodinil

Tomato fruit 1.31-1.33 0 3 0.278 1.28 0.317 1.12 0.365 0.600 0.45

1

 n = number of independent field trials.

2 Values based on total number of samples.

3 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at 

the LOQ. The LOQ was 0.01 ppm for cyprodinil in all matrices.

4 Calculated by the reviewer.

Conclusion: The data adequately support the requested tolerances and proposed use patterns. 

860.1520 Processed Food and Feed

None of the new uses have processed commodities that require a processing study.

860.1550 Harmonization with Codex

No Codex MRLs are established in/on globe artichoke, acerola, feijoa, guava, jaboticaba, 

passionfruit, starfruit, wax jambu, and pomegranate. Canadian and Mexican MRLs have not 

been established for the requested crops. The Agency with be harmonized with Codex on the 

fruit, stone, group 12-12 MRL of 2.0 ppm. 

860.1650 Submittal of Analytical Reference Standards

Analytical standards for cyprodinil (expiration date 7/30/2018) and CGA-304075 (expiration 

date 8/31/2016) are currently available in the EPA National Pesticide Standards Repository

(email communication with T. Cole, ACB, 04/08/2015). 

860.1850/1900 Confined and Field Accumulation in Rotational Crops

DP# D257898, 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. 

In the subsequent field accumulation study, cyprodinil (WDG) was applied to mustard greens at 

four test sites 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
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 14 of 21

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 PBIs 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 analyzed 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 LOQ of 0.05 ppm for 

parent and each metabolite. 

As 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.

860.1550 Proposed Tolerances

The Agency has determined that the residue of concern in plant commodities for the tolerance 

expression is only cyprodinil. Tolerances have been established for residues of cyprodinil in/on 

a variety of crop commodities, at levels ranging 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 

cyprodinil and its metabolite CGA-304075 residues in meat byproducts of cattle, goats, horses 

and sheep. 

Table 8. Tolerance Summary for Cyprodinil

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Tolerances Proposed Under PP#4E8273

Artichoke 4.0 4.0 Artichoke, globe

Guava 1.5 1.5 ---

Passionfruit 1.5 1.5 ---

Feijoa 1.5 1.5 ---

Jaboticaba 1.5 1.5 ---

Wax Jambu 1.5 1.5 ---

Starfruit 1.5 1.5 ---

Acerola 1.5 1.5 ---

Pomegranate 7.0 10 ---

Fruit, stone, group 12-

12

2.0 2.0 ---

References

DP Numbers: 378920

Subject: Cyprodinil. Cyprodinil. Amended Use and Amended Tolerance 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
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 15 of 21

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: 09/15/09

MRID(s): 47644301

DP Numbers: 345970 and 345182

Subject: Cyprodinil. Section 3 Requests for Uses on Tomato, Avocado, Herbs, Root Vegetables, Leaves of 

Root and Tuber Vegetables, Lemon, Lime, Cucurbits, Kiwifruit, Green and Dry Bulb Onions, and 

Strawberries. Registrant’s Response to Conditional Registration on Carrots and Brassica 

Vegetables and Livestock Feeding Study. Summary of Analytical Chemistry and Residue Data. 

From: W. Cutchin

To: W. Cutchin/B. Madden

Dated: 06/04/08

MRID(s): 47161101-47161107 and 47169305-47169311

DP Number: 326346

Subject: Registration: 100-953; PP#8E05012; Cyprodinil on Onions. Review of Revised Label, Field 

Accumulation 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 288773

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: 07/24/03

MRID(s): 45682401, 45721502, 45726101, 45726102, 45795301, 45795302, and 45839801

DP Number: 257898

Subject: PP# 8E05012. Cyprodinil in/on Strawberries and Bulb Vegetables (Crop Group 3). Evaluation of 

Residue Data and Analytical Methods. 

From: S. Levy

To: R. Forrest/S. Brothers

Dated: 02/08/00

MRID(s): 44615602, 44615601, 44867312, 44867314

DP Numbers: 243198

Subject: Cyprodinil. HED Metabolism Assessment Review Committee Meeting of 02/10/98.

From: G. Kramer

To: HED MARC Members

Dated: 03/11/98

MRID(s): None
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 16 of 21

DP Numbers: 233561, 233562, 233928, 233182, 239674, and 236086

Subject: PP# 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: 02/20/98

MRID(s): 44186401, 44186404 and 44186410 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 Methods.

From: G. Kramer

To: C. Welch/ K. Whitby

Dated: 02/13/96

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 - International Tolerances

Appendix II – Tolerance Assessment Calculations

F. DOCUMENT TRACKING

RDI: C. Smith 07/01/15

Petition Number: 4E8273

DP#: 421157

PC Code: 288202

Template Version September 2005
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 17 of 21

Appendix I. International Tolerances

Cyprodinil (PC Code 288202; 03/12/15)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico2 Codex

40 CFR 180.532:

Plant: Cyprodinil (4-cyclopropyl-6-methylN-phenyl-2-pyrimidinamine).

4-cyclopropyl-6-

methyl-N-phenyl-2-

pyrimidinamine

Cyprodinil

The residue 

is fat 

soluble.

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

US Canada Mexico2 Codex

Artichoke, globe 4.0

Guava 1.5 

Passionfruit 1.5

Feijoa 1.5

Jaboticaba 1.5

Wax Jambu 1.5

Starfruit 1.5

Acerola 1.5

Pomegranate 10

Fruit, stone, group 12-12 2.0 2

Completed: M. Negussie; 03/19/15

1

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

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 18 of 21

Appendix II. Tolerance Assessment Calculations.

For each of the crops listed below, the OECD MRL Calculator User Guide (SOP), along with the 

tolerance spreadsheet, was used for calculating recommended tolerances. As specified in the 

SOP, the tolerance calculation is in the region of the 95th percentile of the underlying residue 

distribution, and is more likely to overestimate rather than underestimate the 95th 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 MRL Calculator, the recommended tolerances are 1.5 ppm for guava, 10 ppm 

for pomegranate, and 4.0 ppm for globe artichoke. 
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 19 of 21

Cyprodinil

Guava

US

1.31-1.43 lb ai/A

Total number of data (n) 4

Percentage of censored data 0%

Number of non-censored data 4

Lowest residue 0.360

Highest residue 0.522

Median residue 0.487

Mean 0.464

Standard deviation (SD) 0.071

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.522

- Mean + 4 SD 0.749

- CF x 3 Mean 1.392

Unrounded MRL 1.392

Rounded MRL 1.5

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

0.36 1

0.483 1

0.491 1

0.522 1
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

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Cyprodinil

Pomegranate

US

0.9 lb ai/100 gal1

Total number of data (n) 4

Percentage of censored data 0%

Number of non-censored data 4

Lowest residue 2.560

Highest residue 3.420

Median residue 3.260

Mean 3.125

Standard deviation (SD) 0.384

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 3.420

- Mean + 4 SD 4.662

- CF x 3 Mean 9.375

Unrounded MRL 9.375

Rounded MRL 10

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

2.56 1

3.26 2

3.42 1

1 Total of two applications. One application as a dip with wax (0.45-0.46 lb ai/100 gal) and a second application as a dip with 

no wax (0.45-0.46 lb ai/100 gal). Applications were allowed to dry before the second application was applied. Samples were 

treated and collected on the same day.
Cyprodinil Summary of Analytical Chemistry and Residue Data DP#: 421157

Page 21 of 21

Cyprodinil

Artichoke, globe

US

1.300–1.655 lbs ai/A

Total number of data (n) 4

Percentage of censored data 0%

Number of non-censored data 4

Lowest residue 0.932

Highest residue 1.330

Median residue 1.215

Mean 1.173

Standard deviation (SD) 0.180

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 1.330

- Mean + 4 SD 1.894

- CF x 3 Mean 3.519

Unrounded MRL 3.519

Rounded MRL 4

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

0.932 1

1.14 1

1.29 1

1.33 1