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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDE 

AND TOXIC SUBSTANCES

MEMORANDUM

Date: 21-JAN-2010 

SUBJECT: Difenoconazole. Import Tolerance Request on Mango and Waxapple (also 

known as Wax jambu). Summary of Analytical Chemistry and Residue Data. 

PC Code: 128847 DP Barcode: D366507 

Decision No.: 413927 Registration No.: NA 

Petition No.: 9E7573 Regulatory Action: None 

Risk Assessment Type: NA Case No.: NA 

TXR No.: NA CAS No.: 19446-68-3 

MRID No.: See MRID Summary Table 40 CFR: §180.475 

Ver.Apr.08 

FROM: Bonnie Cropp-Kohlligian, Environmental Scientist 

 Risk Assessment Branch 4 

 Health Effects Division (7509P) 

 

THROUGH: Susan V. Hummel, Chemist/Senior Scientist 

 Risk Assessment Branch 4 

 Health Effects Division (7509P) 

TO: Rosemary Kearns/Tony Kish (RM 22) 

 Fungicide Branch 

 Registration Division (7505P) 

MRID Summary Table 

MRID No. Study Type Comments 

47760601 860.1500 Waxapple New DER; 47760601.der.doc 

47760602 860.1500 Mango New DER; 47760602.der.doc 
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This document was originally prepared under contract by Dynamac Corporation (1901 Research 

Boulevard, Suite 220; Rockville, MD 20850). 

Dynamac Primary 

Reviewer: 

Date: 10/28/2009 

Sandra Hastings

Dynamac QC 

Reviewer: 

Date: 10/28/2009 

Danilo Martinez 

The document has been reviewed by the Health Effects Division (HED) and revised to reflect 

current Office of Pesticide Programs (OPP) policies. 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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Executive Summary

Difenoconazole is a broad spectrum fungicide belonging to the triazole group of fungicides 

(Group 3). It is currently registered in the U.S. for use as a seed treatment on cereal grains, 

canola, and cotton and for foliar applications on pome fruits, sugar beets, fruiting vegetables, and 

tuberous and corm vegetables. A petition (PP#8F7482) is pending for foliar uses on bulb 

vegetables, Brassica leafy vegetables, cucurbit vegetables, citrus fruits, grapes, pistachios, and 

tree nuts. The mode of action of difenoconazole is as a demethylation inhibitor of sterol 

biosynthesis which disrupts membrane synthesis by blocking demethylation. 

Under PP#9E7573, Syngenta Crop Protection, Inc. is proposing the establishment of import 

tolerances for residues of difenoconazole [1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole] in/on the following raw agricultural commodities: 

Mango, fruit .........................................................................0.09 ppm 

Waxapple, fruit ....................................................................1.5 ppm 

The end-use product (EP) for use on mangos grown in Brazil is Score®, an emulsifiable 

concentrate (EC) formulation containing 250 g ai/L. Up to three foliar spray applications at a 

target rate of 0.11 lb ai/A/application (0.125 kg ai/ha/application), with a 14-day retreatment 

interval (RTI), may be made to mature mango trees for a total seasonal rate of 0.33 lb ai/A 

(0.375 kg ai/ha) using ground equipment in 500 to 1,000 L/ha spray volume (53 to 107 gal/A 

which is considered a concentrated spray volume) and a 7-day preharvest interval (PHI). The 

use pattern is supported by adequate residue data from crop field trials conducted in Brazil. 

The EP for use on waxapples grown in Taiwan is ‘Hao Jia Zan Azoxystrobin + Difenoconazole’, 

a soluble concentrate (SC) formulation containing 12.5% w/v difenoconazole and 20% w/v 

azoxystrobin. The information for waxapple use in Taiwan is incomplete, however, the 

submitted field trial data will support up to eight foliar applications of a 125 g/L SC formulation 

of difenoconazole to mature waxapple trees at a target rate of 0.34 lb ai/A/application (0.39 kg 

ai/ha/application), with 6- to 8-day RTI, for a total seasonal rate of 2.74 lb ai/A (3.07 kg ai/ha) 

and a 12-day PHI. Applications may be made using ground equipment in a 2,000 L/ha spray 

volume (214 gal/A which is considered a dilute spray volume), without an adjuvant. Consistent 

with the submitted field trial data, applications should be restricted to fruit protected with 

exclusion net bags or otherwise bagged fruit. This review addresses the proposed use of 

difenoconazole only. 

Tolerances for difenoconazole are currently established under 40 CFR §180.475. Tolerances for 

plant commodities are established under §180.475(a)(1), and are expressed in terms of 

difenoconazole per se. Tolerances are established for raw agricultural and processed 

commodities, including barley, sugar beet, canola, corn, pome fruit, fruiting vegetable, and 

tuberous and corm vegetable commodities, and range 0.01-4.5 ppm. Import tolerances are 

established for banana, grape, papaya, and rye grain, and range 0.10-0.30 ppm. Tolerances for 

livestock commodities are established under §180.475(a)(2) and are expressed in terms of 

difenoconazole and its metabolite, CGA-205375 [1-[2-chloro-4-(4-chloro-phenoxy)phenyl]-2-

[1,2,4]triazol-1-yl-ethanol]. Livestock tolerances for tissues, milk, and egg range 0.05-0.20 ppm. 

Time-limited tolerances, expressed in terms of difenoconazole per se, are established under 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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§180.475(b) in support of Section 18 emergency exemptions for use on almond, cantaloupe, 

cucumber, and watermelon and range 0.05-5.0 ppm. 

The nature of the residue in plants is understood based on acceptable plant metabolism studies 

reflecting foliar applications in canola, grape, potato, tomato, and wheat, and seed treatment in 

wheat. HED concludes that the residue of concern for both tolerance enforcement and risk 

assessment for crops included in this petition is difenoconazole per se. The nature of the residue 

in livestock is understood based on acceptable goat and hen metabolism studies. The residues of 

concern for both tolerance setting and risk assessment for livestock commodities are 

difenoconazole per se and its metabolite CGA-205375. 

Because difenoconazole is a triazole compound, HED requires that samples from any 

metabolism, feeding, field trial, and/or processing studies be analyzed for the triazole 

metabolites, triazolylalanine (TA), triazolyl acetic acid (TAA), and 1,2,4-triazole (1,2,4-T). 

These data are needed for risk assessment only. HED issued guidance on the residue chemistry 

data requirements for the triazole-based metabolites under DP# 327788 (4/25/06, M. Doherty) 

and has requested submission of these data for all pending uses on record within the Agency as 

of September 1, 2005. The submitted waxapple field trial study did not include analysis for the 

three triazole metabolites; however, these data will not be required to support this petition since 

there is no consumption for waxapple in the current dietary exposure evaluation model. The 

submitted mango field trial study, which was conducted in 2003, did not include analysis for the 

three triazole metabolites; however, the study is not considered upgradable for this purpose. 

HED has determined (DP# 371613, 01/21/2010, T. Morton) that the proposed use of 

difenoconazole on mango does not result in an increase in dietary exposure estimates for triazole 

metabolites in/on mangos which was incorporated into the last dietary exposure analyses for the 

triazole metabolites (M. Negussie, 28 Oct. 2009) and which is currently based on existing uses of 

myclobutanil and tebuconazole on mangos. Additional triazole metabolite data for the proposed 

use of difenoconazole on mango is not expected to result in increases to the current dietary 

exposure estimates for triazole metabolites; hence, additional triazole metabolite data will not be 

required to support the proposed use of difenoconazole on mango. 

An adequate tolerance enforcement method, method AG-575B, is available for crop 

commodities. The method determines residues of difenoconazole per se in/on crop commodities 

by gas chromatography with nitrogen-phosphorus detection (GC/NPD). The method limits of 

quantitation (LOQs) are 0.01-0.05 ppm. A confirmatory GC method with mass-selective 

detection (MSD) is also available for crop commodities. Samples from the submitted the crop 

field trials were analyzed for residues of difenoconazole using a high performance liquid 

chromatography method with tandem mass spectrometry detection (LC/MS/MS), Syngenta REM 

147.08, or a similar method. The methods are adequate for data collection based on acceptable 

concurrent method recoveries. The LOQ was 0.01 ppm for difenoconazole in mango and 

waxapple. 

Analytical standards for difenoconazole and its metabolite CGA-205375 are currently available 

in the EPA National Pesticide Standards Repository. 

There are no feedstuffs associated with the foreign uses of difenoconazole on mango in Brazil 

and waxapple in Taiwan. Therefore, no livestock enforcement methods, storage stability data, or 

feeding studies are required to support this petition. 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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Mangos and waxapple are not typically rotated and rotational crop restrictions are not relevant 

for foreign uses. Therefore, a discussion pertaining to the need for rotational crop data is not 

germane to this petition. 

 

Samples of mango and waxapple from the submitted crop field trials were stored frozen for up to 

four months prior to analysis for difenoconazole. Adequate storage stability data are available 

for difenoconazole to conclude that residues are stable in/on all raw agricultural crop 

commodities for up to one year. 

HED is unable to assess the adequacy of the submitted field trial data for waxapple because the 

use directions have not been fully elucidated. Syngenta is required to provide label use 

information as detailed under ‘Directions for Use’ section. Assuming that the use directions for 

waxapple in Taiwan, once fully elucidated, will comport with the submitted field trial data, HED 

tentatively recommends for the proposed import tolerance of 1.5 ppm for waxapple. No Codex, 

Canadian, and Mexican MRLs have been established for residues of difenoconazole in/on 

waxapple. 

The submitted field trial data for mango are adequate and reflect the proposed use of Score® on 

mango in Brazil. The residue data from the trials conducted will support the proposed import 

tolerance of 0.09 ppm for mango. A Codex MRL for residues of difenoconazole per se has been 

established at 0.07 ppm for mango. Canadian and Mexican MRLs have been established for 

difenoconazole; however, no MRLs have been established for mango. The Codex MRL for 

residues of difenoconazole per se in/on mango is based on the same dataset considered herein; 

however, the reviewer has been advised (personal communication with S. Funk 

OPP/HED/RAB3 via email dated 11/04/2009) that the Joint FAO/WHO Meeting on Pesticide 

Residues (JMPR) uses field trial data in the NAFTA calculator and may interpret the outcomes 

differently than HED. JMPR does not accept the independence of samples from the same 

location; hence, JMPR used the following four data points from the four 2003 mango field trials 

conducted in Brazil in the NAFTA calculator: 0.025 ppm, 0.025 ppm, 0.035 ppm, and 0.04 ppm 

. From these data, the NAFTA calculator gives 0.06 ppm, which JMPR did not accept. JMPR 

typically goes higher than the NAFTA calculator where there are few samples and so established 

the 0.07 ppm MRL for mango. Harmonization with the established Codex MRL of 0.07 ppm for 

residues of difenoconazole in/on mango is recommended for mango. 

Regulatory Recommendations and Residue Chemistry Deficiencies

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

revised Section B for waxapple (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 import tolerances for residues of difenoconazole resulting from the 

uses on mango in Brazil and waxapple in Taiwan: 

Mango ..................................................................................0.07 ppm 

Waxapple .............................................................................1.5 ppm 

A human health risk assessment is forthcoming. 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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Notes to PM: 

1. With regards to the use on mangos in Brazil, HED notes that Mexico and not Brazil 

is the largest importer of mangos into the U.S. Since only data from Brazil were submitted, 

the registrant should be made aware that HED makes no ascertain as to the adequacy of 

the recommended tolerance to cover residues incurred in other geographical regions of 

South America or Mexico from the same or similar use. 

2. An error was found in MRID 47760601, Section 1.3 Test Item, bottom of Page 6 of 

66. The stated nominal/actual formulation content in Amistar Top 325 SC of 

difenoconazole and azoxystrobin are reversed. According to the label, Amistar Top 325 SC 

contains 125 g/L of difenoconazole and 200 g/L azoxystrobin. The MRID should be 

corrected. 

3. The registrant should be reminded that because difenoconazole is a triazole 

compound, HED requires that samples from any metabolism, feeding, field trial, and/or 

processing studies be analyzed for the triazole metabolites triazolylalanine (TA), triazolyl 

acetic acid (TAA), and 1,2,4-triazole (1,2,4-T). Guidance has been issued concerning these 

residue chemistry data requirements for the triazole-based metabolites under DP# 327788 

(4/25/06, M. Doherty) and data submitted in support of future uses of difenoconazole will 

be accessed accordingly. 

4. The registrant should be reminded that magnitude of the residue data for papaya, 

as a representative crop of the tropical fruit crops group, have been deemed adequate to 

support the same or substantially similar use on mango (among other tropical fruits) and 

the establishment of a separate mango tolerance. An import tolerance is currently 

established under §180.475(a)(1) for residues of difenoconazole in/on papaya at 0.3 ppm. 

860.1200 Directions for Use - Waxapple 

• Syngenta must submit a complete description of the use of difenoconazole on waxapple 

grown in Taiwan (a translated label or complete Section B). As required by the NAFTA 

Guidance Document on Data Requirements for Tolerances on Imported Commodities in 

the United States and Canada (December 2005), it is necessary to submit copies of 

registered/approved label(s) translated to English. The information must include, but is 

not limited to, the maximum single application rate, the maximum annual application 

rate, application timing (as it relates to plant growth stage), retreatment interval, 

application tank-mix preparation, volume of spray mix per unit area, application 

equipment, and the preharvest interval. The application rates should be expressed in 

units of pounds of active ingredient per acre (or kilograms per hectare). 

• Syngenta must submit a complete description of the use of difenoconazole on waxapple 

grown in Taiwan consistent with the use profile of the submitted field trial data (MRID 

47760601). The submitted field trial data will support eight foliar applications of a 125 

g/L suspension concentrate (SC) formulation of difenoconazole at a target rate of 0.39 kg 

ai/ha/application (0.34 lb ai/A/application), with 6- to 8-day retreatment intervals, for a 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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total rate of 3.07 kg ai/ha (2.74 lb ai/A) and a 12-day PHI. Applications may be made 

using ground equipment in 2,000 L/ha spray volumes (214 gal/A which is considered a 

dilute spray volume), without an adjuvant. 

• Consistent with the submitted field trial data, applications should be restricted to fruit 

protected with exclusion net bags or otherwise bagged fruit. 

860.1550 Proposed Tolerances 

• The proposed tolerances should be revised to reflect the recommended tolerance levels 

and correct commodity definitions as specified in Table 6. 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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Background

The chemical structure and nomenclature of difenoconazole and its regulated livestock 

metabolite CGA-205375, and the physicochemical properties of the technical grade of 

difenoconazole are presented in Tables 1 and 2. 

Table 1. Difenoconazole Nomenclature. 

Chemical structure 

O O

O

N N Cl

N

CH3

Cl

Common name Difenoconazole 

Company experimental name CGA-169374 

IUPAC name 1-({2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-

1H-1,2,4-triazole 

CAS name 1-[[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl]methyl]- 

1H-1,2,4-triazole 

CAS registry number 119446-68-3 

End-use products (EP) Score® - for mango grown in Brazil. 

‘Hao Jia Zan Azoxystrobin + Difenoconazole’ - for waxapple grown in Taiwan 

Chemical structure of CGA205375 livestock metabolite 

O

Cl N N

N OH Cl

Table 2. Physicochemical Properties of Difenoconazole. 

Parameter Value Reference 

Melting point 78.6 oC DP#s 172067 and 178394, 10/26/92, R. 

Lascola pH 6-8 at 20 oC (saturated solution) 

Density 1.37 g/cm3 at 20 oC 

Water solubility 3.3 ppm at 20 oC 

Solvent solubility g/100 mL at 25 oC: 

n-hexane: 0.5 

1-octanol: 35 

toluene: 77 

acetone: 88 

ethanol: 89 

Vapor pressure 2.5 x 10-10 mm Hg at 25 oC 

Dissociation constant, pKa Reported as <0 in MRID 42090003 which was previously reviewed in DP#s 172067 

and 178394; however, questions have arisen concerning this value. Re-examination of 

MRID 42090003 found that the product chemistry data study to support the reported 

dissociation constant for the technical grade of difenoconazole was not included. New 

data are expected. 

Octanol/water partition 

coefficient, Log(KOW) 

4.2 at 25 oC DP#s 172067 and 178394, 10/26/92, R. 

Lascola 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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Table 2. Physicochemical Properties of Difenoconazole. 

Parameter Value Reference 

UV/visible absorption spectrum λmax at about 200 and 238 nm 

(in methanol at 26 oC) 

PMRA Proposed Regulatory Decision 

Document on Difenoconazole, 4/14/99 

(PRDD99-01) 

860.1200 Directions for Use

A list of the end-use products (EPs) relevant to this import tolerance petition is presented in 

Table 3a. A summary of the use directions for these EPs is presented in Table 3b. 

Table 3a. Summary of Difenoconazole End-Use Products Proposed for Use on Mango and Waxapple.

Trade Name Country a.i. (% of 

formulation) 

Formulation 

Type

Proposed 

Crops 

Target Pests Label 

Date 

Score® Brazil 25% 

 (250 g ai/L) 

EC Mango Powdery mildew and 

anthracnose 

10/30/02 

(Hao Jia Zan) 1

Azoxystrobin + 

Difenoconazole 

Taiwan 12.5% SC Waxapple Anthracnose undated, 

Section B 

1

 The Taiwan end-use product is a soluble concentrate formulation containing 12.5% w/v difenoconazole and 20% w/v 

azoxystrobin. 

Table 3b. Summary of Proposed Directions for Use of Difenoconazole. 

Applic. Timing, 

Type, and 

Equip. 

Product 

[Formulation] 

Applic. 

Rate 

(lb ai/A) 

[g ai/ha] 

Max. No. 

Applic. per 

Season 

Max. Seasonal 

Applic. Rate 

(lb ai/A) 

[g ai/ha] 

PHI 

(days) 

Use Directions and 

Limitations 

Mango 

Foliar; 

Ground 

(500-1,000 L/ha 

spray volume) 

Score® 

[250 g ai/L 

EC] 

0.022-

0.11 

[25-125]

3 0.33 

[375] 7 

Applications must start 

immediately after the 

engorgement of floral 

gems or before flowers 

bloom, using smallest 

dose in the first 

applications to control 

powdery mildew and a 

larger dose to control 

anthracnose; 14-day RTI. 

Waxapple 

Foliar; 

equipment not 

specified (NS) 

Hao Jia Zan

[12.5% w/v 

SC] 

3,000x 

dilution1 5 NS 30 Only to be applied during 

fluorescence; 7-day RTI. 

1

 The application rate could not be determined as the Section B only reported the concentration to be applied. 

Conclusions. The submitted use direction information for Score®, the EP for use on mango in 

Brazil, is adequate to allow evaluation of the residue data. The submitted mango field trial data 

reflect the foreign use pattern. However, the use direction information for Hao Jia Zan 

Azoxystrobin + Difenoconazole, the EP for use on waxapple in Taiwan is not adequate to allow 

evaluation of the residue data. Specifically, the use rate on waxapple could not be determined 

from the Taiwan use pattern as summarized in Section B; only a concentration (dilution) level 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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was reported. A translated label (or complete Section B) which specifies the use rate (in g ai/ha 

or lb ai/A) on waxapple in Taiwan must be submitted before HED can determine if the field trial 

data support the proposed import tolerance. The submitted field trials reflect a maximum total 

rate of 3.07 kg ai/ha (2.74 lb ai/A) and a 12-day PHI; the PHI reported in Section B is 30 days 

for waxapple. 

860.1300 Nature of the Residue - Plants

Residue Chemistry Memo DP# 340379, 8/9/07, W. Wassell and M. Sahafeyan 

MARC Decision Memo, 7/22/94, G. Kramer 

The nature of the residue in plants is understood based on acceptable plant metabolism studies 

reflecting foliar applications in canola, grape, potato, tomato, and wheat and seed treatment in 

wheat. Based on the results of available plant metabolism studies, the petitioner has proposed 

that difenoconazole is metabolized in plants by the hydroxylation of the phenyl ring and/or 

cleavage of the dioxolane ring followed by cleavage of the carbon-carbon bridge between the 

phenyl and triazole rings. 

Previously, when the first foliar uses of difenoconazole on crop commodities were proposed 

(DP# 340379), HED re-evaluated the available plant metabolism data to determine if residues 

other than difenoconazole needed to be included in the tolerance expression and/or the risk 

assessment and concluded that the residue of concern for both tolerance enforcement and risk 

assessment for the crops (fruiting vegetables, pome fruits, sugar beets, tuberous and corm 

vegetables, and imported papaya) in the petition (PP#6F7115) under consideration. In keeping 

with the previous decision, HED concludes that the residue of concern for both tolerance 

enforcement and risk assessment for the crops included in this petition is difenoconazole per se. 

860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo DP# 340379, 8/9/07, W. Wassell and M. Sahafeyan 

MARC Decision Memo, 7/22/94, G. Kramer 

Residue Chemistry Memo DP#s 203644 and 203645, 6/16/94, G. Kramer 

Residue Chemistry Memo DP#s 172067 and 178394, 10/26/92, R. Lascola 

The nature of the residue in livestock is understood based on acceptable goat and hen 

metabolism studies. The data were originally evaluated in support of seed treatment uses only, 

and HED concluded that the residue of concern in livestock commodities was difenoconazole

per se. When the first foliar uses of difenoconazole on crop commodities were proposed (DP# 

340379), HED re-evaluated the livestock metabolism data and concluded that the residues of 

concern for both tolerance setting and risk assessment for livestock commodities are 

difenoconazole and metabolite CGA-205375. 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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860.1340 Residue Analytical Methods

Crop Commodities 

Residue Chemistry Memo DP# 356135, 9/17/09, B. Cropp-Kohlligian 

Residue Chemistry Memo DP# 340379, 8/9/07, W. Wassell and M. Sahafeyan 

Enforcement methods: An adequate enforcement method, GC/NPD method AG-575B, is 

available for the determination of residues of difenoconazole per se in/on plant commodities. An 

adequate enforcement method, GC/MSD method AG-676A, is also available for the 

determination of residues of difenoconazole per se in/on canola and barley commodities. A 

confirmatory method, GC/MSD method AG-676, is also available. The LOQs are 0.01-0.05 

ppm. 

Data collection methods: Samples of waxapple from the Taiwan field trials were analyzed for 

residues of difenoconazole using LC/MS/MS method, REM 147.08. This method was 

previously reviewed and determined an alternative enforcement method for difenoconazole in 

plants (DP# 340379). Briefly, waxapple fruits were extracted with methanol:concentrated 

ammonium hydroxide (8:2, v:v) at reflux. An aliquot of the extract was diluted with water for 

cleanup by solid-phase extraction (SPE; Oasis HLB cartridge). Residues of difenoconazole were 

quantitated by LC/MS/MS analysis. The validated LOQ was 0.01 ppm for difenoconazole in 

waxapple. The limit of detection was not reported. 

 

Samples of mangos from the Brazil crop field trials were also analyzed for residues of 

difenoconazole using an LC/MS/MS method. This method varies from Method REM 147.08, in 

that extraction does not include ammonium hydroxide and was not conducted at reflux, and a 

SPE cleanup step was not performed. Briefly, mango fruits were homogenized/extracted with 

acetone:water (2:1, v:v) and centrifuged. An aliquot of the extract was evaporated and 

redissolved in acetonitrile (ACN):water (1:1, v:v) for LC/MS/MS analysis. The validated LOQ 

was 0.01 ppm for difenoconazole in mango. 

Although mango fruits with stones removed were analyzed, consistent with the food portion of 

mango fruits to be analyzed according to PAM Vol. I, Section 102, the residue results were 

calculated and reported as difenoconazole in/on whole fruit. Difenoconazole residues in/on 

whole fruits were calculated by dividing the weight of the whole fruit by the weight of the fruit 

without the stone and then multiplying by the residue value found in/on the fruit without the 

stone. Only the calculated whole fruit results were provided in the study submission. 

Both methods are adequate for data collection based on acceptable concurrent recovery data. 

The fortification levels used in concurrent method recovery are adequate to bracket (within an 

order of magnitude) expected residues in mango and waxapple. 

Conclusions. An adequate tolerance enforcement method is available for determination of 

residues of difenoconazole per se in crop commodities, and samples from the crop field trial 

studies were analyzed for residues of difenoconazole using acceptable methods. 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

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860.1360 Multiresidue Methods

Residue Chemistry Memo DP#s 172067 and 178394, 10/26/92, R. Lascola 

Email from C. Stafford (Analytical Chemistry Branch) to B. Cropp-Kohlligian dated 9/2/09 

Multiresidue methods (MRM) testing data (MRID 42090054) were previously submitted in 

conjunction with PP#2E4051 (DP#s 172067 and 178394, 10/26/92, R. Lascola). The study 

investigated the recovery of difenoconazole and its metabolites CGA-205374, CGA-205375, and 

CGA-189138 through the MRM methods of PAM Vol. I. Based on the study results, HED 

concluded, as did the petitioner, that the MRM methods were not likely to be appropriate for 

determining residues of difenoconazole and its related compounds in plant and livestock tissues. 

The study was forwarded to FDA for further review. Difenoconazole is not listed in the most 

recent PESTDATA (1999). 

In contradiction to the MRM study evidence, Analytical Chemistry Branch (ACB) has noted 

(Email from C. Stafford (ACB) to B. Cropp-Kohlligian dated 9/2/09) that (1) FDA routinely 

monitors for difenoconazole by GC/MS using their current modified Luke procedures which are 

not in the published PAM I manual; (2) difenoconazole has also been tested through the 

QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method which is just beginning 

to be implemented in the FDA field labs using LC/MS/MS; and (3) the USDA-PDP program 

labs monitor for difenoconazole; the California Department of Food and Agriculture (CDFA), a 

participating laboratory, uses a multiresidue method with LC/MS analysis. Based on these facts, 

HED accepts that difenoconazole is recoverable through existing multiresidue methods, although 

the evidence is non-guideline and a conclusion concerning whether recovery is complete (>80%) 

cannot be reached. No additional MRM testing data are required at this time. 

860.1380 Storage Stability

Residue Chemistry Memo DP# 340379, 8/9/07, W. Wassell and M. Sahafeyan 

Adequate storage stability data are available indicating that residues of difenoconazole are stable 

at -20 °C for at least two years in/on cotton seed, oil, and meal; potato tuber; tomato; and wheat 

forage, grain, and straw. Data are also available indicating that difenoconazole residues are 

stable at -20 °C for at least one year in/on banana, lettuce, and soybean seed. HED previously 

concluded (DP# 340379) that these data represent sufficient diverse crops (a leafy vegetable, a 

fruit, a root crop, a non-oily grain, and an oilseed) to allow translation of storage stability data 

for difenoconazole to all raw agricultural crop commodities for a one-year storage interval. The 

available storage stability data for the two-year storage interval are not sufficient to allow 

translation to all raw agricultural commodities because no data are available for a leafy 

vegetable. 

The storage durations and conditions of samples from the crop field trials submitted to support 

this import tolerance petition are presented in Table 4. 

Table 4. Summary of Storage Conditions and Durations of Samples from Crop Field Trial Studies. 

Matrix Storage Temperature 

 (°C) 

Actual Storage Duration Interval of Demonstrated 

Storage Stability 

Mango ≤-18 51-60 days (1.7-2.0 months) Up to one year.
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 13 of 23 

Table 4. Summary of Storage Conditions and Durations of Samples from Crop Field Trial Studies. 

Matrix Storage Temperature 

 (°C) 

Actual Storage Duration Interval of Demonstrated 

Storage Stability 

Waxapple ≤-18 59-113 days (1.9-3.7 months) 

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

storage conditions and durations of samples of mango and waxapple from the submitted crop 

field trial studies. Based on the submitted data, there are no storage stability issues, and no 

corrections need be applied to the crop field trial results. 

860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with foreign uses on mango or waxapple. Therefore, 

data requirements pertaining to meat, milk, poultry, and eggs are not relevant to this tolerance 

petition. 

860.1500 Crop Field Trials

DER Reference: 47760601.der.doc (waxapple) 

 47760602.der.doc (mango) 

Table 5. Summary of Residue Data from Crop Field Trials with Difenoconazole. 

Crop matrix Total Applic. 

Rate in lb ai/A 

[g ai/ha] 

PHI 

(days) 

Residue Levels (ppm) 

N Min. Max. HAFT1 Median Mean Std. 

Dev. 

Mango (Brazil use = 375 g ai/ha (0.335 lb ai/A) total application rate, 7-day PHI) 

Mango2 0.33 

[375 g ai/ha] 

7 8 0.01 0.04 0.04 0.03 0.03 0.01 

Waxapple (Taiwan use = additional use pattern information is required, 30-day PHI) 

Waxapple, 

paper-bagged 

fruit3 2.74 

[3.07 kg ai/ha] 12 

6 0.08 0.16 0.14 0.13 0.12 0.03 

Waxapple, netbagged fruit 6 0.66 1.27 0.97 0.80 0.85 0.23 

1

 HAFT = Highest average field trial result. 2

 Although mango fruits with stones removed were analyzed, consistent with the food portion of mango fruits to be analyzed 

according to PAM Vol. I, Section 102, the residue results were calculated and reported as difenoconazole in/on whole fruit. 

Difenoconazole residues in/on whole fruits were calculated by dividing the weight of the whole fruit by the weight of the fruit

without the stone and then multiplying by the residue value found in/on the fruit without the stone. 

3

 Fruits were bagged after the second of eight applications. 

Mango 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 14 of 23 

Four mango trials were conducted in the northeast region of Brazil during the 2003 growing 

season. At each test location, three foliar applications of a 250 g/L EC (Score®) formulation of 

difenoconazole were made to established and fruit-bearing mango trees at a target rate of 125 g 

ai/ha/application (0.11 lb ai/A/application), with a 14-day retreatment interval, for a total rate of 

375 g ai/ha (0.33 lb ai/A). The single and total application rates are 1x the label rates. 

Applications were made using ground equipment in 1,000 L/ha (107 gal/A) spray volumes; the 

use of an adjuvant was not reported. Mature mango fruits were harvested 7 days after the last 

application (DALA). Additional samples were collected from two trials at 0, 3, 5, and 9 DALA 

to generate residue decline data. 

Samples of mango fruits with stones removed were analyzed for residues of difenoconazole 

using a high performance liquid chromatography method with tandem mass spectrometry 

detection (LC/MS/MS Method POPIT MET.033.Rev03). The method is adequate for data 

collection based on acceptable concurrent method recoveries. The fortification levels used in 

concurrent method validation adequately bracketed the expected residues in/on treated mango. 

The validated LOQ was 0.01 ppm. The mango samples were not analyzed for triazole 

metabolites. 

Although mango fruits with stones removed were analyzed, consistent with the food portion of 

mango fruits to be analyzed according to PAM Vol. I, Section 102, the residue results were 

calculated and reported as difenoconazole in/on whole fruit. Difenoconazole residues in/on 

whole fruits were calculated by dividing the weight of the whole fruit by the weight of the fruit 

without the stone and then multiplying by the residue value found in/on the fruit without the 

stone. Only the calculated whole fruit results were provided in the study submission. This 

calculation will overestimate the residues of difenoconazole in/on mango fruits with stones 

removed; however, based on the single example calculation provided in the study submission, 

the reviewer estimates that mango stones are not likely to exceed 20% by weight of the whole 

fruit, and given the low residue levels found, the overestimation is not considered significant in 

this case. 

 

The collected samples were stored frozen prior to residue analysis; storage durations are reported 

in Table 4. Adequate storage stability data are available on a wide variety of raw agricultural 

crop commodities which support the mango studies. 

The results indicate that residues of difenoconazole ranged 0.01-0.04 ppm in/on mango fruits 

harvested 7 days following the last of three foliar applications of Score® at a total rate of 375 g 

ai/ha (0.33 lb ai/A). The decline data indicate that residues generally appear to decline in mango 

with later sampling intervals; residues were 0.06-0.09 ppm at the 0-day PHI and 0.01-0.04 ppm 

at the 9-day PHI. 

Conclusions. The submitted field trial studies are adequate and reflect the use pattern for mango 

in Brazil. An acceptable method was used for the determination of residues of difenoconazole, 

and the sample storage conditions and durations for difenoconazole analyses are supported by 

adequate storage stability data. The submitted field trial data will support the proposed import 

tolerance of 0.09 ppm for mango; the tolerance calculation is presented in Appendix I. 

The requirements for geographic representation of crop field trials for import tolerances are 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 15 of 23 

specified in the NAFTA Guidance Document on Data Requirements for Tolerances on Imported 

Commodities in the United States and Canada (December 2005). Using data obtained from Fruit 

and Tree Nuts Situation and Outlook Yearbook (USDA, 2008) and averaging data from the past 

5 years (crop seasons 2003-2007), mango imports account for >75% of the total U.S. 

consumption. Imports from Brazil account for 9.4% of all mango imports; Mexico accounts for 

62% of all imported mango. Because the maximum percent of the diet for mango is <0.05%, 

three trials would be required for an import tolerance. The four field trials conducted in Brazil 

are adequate 

. 

Waxapple (also known as Wax jambu) 

Three waxapple trials were conducted in Taiwan during the 2006-2007 growing season. 

Thiamethoxam, azoxystrobin, and difenoconazole were simultaneously applied in these trials 

either as co-active ingredients or as tank mixes. Although residue data were provided for 

azoxystrobin and thiamethoxam, this document only addresses the residue data for 

difenoconazole. 

At each test location, established and fruit-bearing waxapple trees were treated with eight foliar 

applications of a 125 g/L suspension concentrate (Amistar Top 325 SC) formulation of 

difenoconazole at a target rate of 0.39 kg ai/ha/application (0.34 lb ai/A/application), with 6- to 

8-day retreatment intervals, for a total rate of 3.07 kg ai/ha (2.74 lb ai/A). Applications were 

made using ground equipment in 2,000 L/ha (214 gal/A) spray volumes, without an adjuvant. 

Waxapple fruit samples were harvested 12 days after the last (8th) application. 

 

The study was designed to allow collections of “bagged” vs. “unbagged” fruit samples. 

However, “unbagged” waxapple fruit was covered with a net bag which allowed chemical 

penetration but prevented fruit fly damage, and “bagged” fruits were covered with a paper bag 1-

2 days after the second application. Hence treated samples were either net-bagged or paperbagged waxapple fruits. Note: The plot histories noted that the trees were normally treated with 

imidacloprid and methomyl for insect control so it is not certain that the use of net bags to 

prevent fruit fly damage is a consistent agricultural practice for waxapple grown in Taiwan. 

The harvested waxapple samples were analyzed for residues of difenoconazole using a high 

performance liquid chromatography method with tandem mass spectrometry detection 

(LC/MS/MS Method REM 147.08). The method was adequate for data collection based on 

acceptable concurrent method recoveries. The fortification levels used in concurrent method 

validation adequately bracketed (within an order of magnitude) the expected residues in/on 

treated waxapple. The validated LOQ was 0.01 ppm. The waxapple samples were not analyzed 

for triazole metabolites. 

 

The collected samples were stored frozen prior to residue analysis; storage durations are reported 

in Table 4. Adequate storage stability data are available on a wide variety of raw agricultural 

crop commodities which support the waxapple studies. 

The results indicate that residues of difenoconazole ranged 0.66-1.27 ppm in/on net-bagged 

samples and 0.08-0.16 ppm in/on paper-bagged samples of waxapples harvested 12 days 

following the last of eight foliar applications of Amistar Top 325 SC at a total rate of 2.74 lb 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 16 of 23 

ai/A. No residue decline data were provided to determine residue levels that may occur at 

various preharvest intervals. 

Conclusions. HED is unable to assess the adequacy of the submitted field trial data for waxapple 

because the use directions have not been fully elucidated. Syngenta is required to provide label 

use information as detailed under ‘Directions for Use’ section. Assuming that the use directions 

for waxapple in Taiwan will match the submitted field trial data, HED tentatively recommends 

for the proposed import tolerance of 1.5 ppm for waxapple. The tolerance calculation using 

residues in net-bagged waxapple is presented in Appendix I. 

The requirements for geographic representation of crop field trials for import tolerances on 

waxapple are not included in the NAFTA Guidance Document on Data Requirements for 

Tolerances on Imported Commodities in the United States and Canada (December 2005). 

However, it can be assumed that >75% of waxapple in the U.S. is imported and that the 

maximum percent of the diet for waxapple is likely <0.05%; therefore, the three trials conducted 

in Taiwan would be considered acceptable to support an import tolerance. 

860.1520 Processed Food and Feed

HED does not require residue data for any processed commodities associated with mango or 

waxapple. Therefore, data requirements for processed food and feed are not relevant to this 

tolerance petition. 

860.1650 Submittal of Analytical Reference Standards 

Analytical standards for difenoconazole (expiration 7/1/2010) and its metabolite CGA-205375 

(expiration 4/30/2010) are currently available in the EPA National Pesticide Standards 

Repository (personal communication with Dallas Wright, ACB, 6/23/09). 

860.1850 and 860.1900 Confined and Field Accumulation in Rotational Crops

Mango and waxapple are not typically rotated, and rotational crop restrictions are not relevant 

for foreign uses, therefore, no data pertaining to rotational crops are required to support this 

petition. 

860.1550 Proposed Tolerances

Tolerances for plant commodities are established under §180.475(a)(1), and are expressed in 

terms of difenoconazole per se. The tolerance expression proposed by Syngenta is appropriate. 

The tolerances proposed by Syngenta are listed in Table 6, along with the tolerance levels 

recommended by HED and corrected commodity definitions. 

The data for waxapple could not be evaluated against the use pattern, because an insufficient 

Section B was provided for the Taiwan label. However, the available data will support the 

proposed tolerances for waxapple at 1.5 ppm. The tolerance spreadsheet in the Agency’s

Guidance for Setting Pesticide Tolerances Based on Field Trial Data was utilized for 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 17 of 23 

determining appropriate tolerance levels for waxapple (see Appendix I). No Codex, Canadian, 

and Mexican MRLs have been established for residues of difenoconazole per se in/on waxapple. 

Adequate data reflecting the use pattern in Brazil are available for mango. These field trial data 

were entered into the tolerance spreadsheet in accordance with the Agency’s Guidance for 

Setting Pesticide Tolerances Based on Field Trial Data to determine the appropriate tolerance 

level for mango (see Appendix I), which supported the proposed tolerance for mango at 0.09 

ppm. A Codex MRL for residues of difenoconazole per se has been established at 0.07 ppm for 

mango; Canadian and Mexican MRLs have been established for difenoconazole; however, no 

MRLs have been established for mango. The Codex MRL for residues of difenoconazole per se 

for mango is based on the same dataset considered herein; however, the reviewer has been 

advised (personal communication with S. Funk OPP/HED/RAB3 via email dated 11/04/2009) 

that the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) uses field trial data in the 

NAFTA calculator and may interpret the outcomes differently than HED. JMPR does not accept 

the independence of samples from the same location; hence, JMPR used the following four data 

points from the four 2003 mango field trials conducted in Brazil in the NAFTA calculator: 0.025 

ppm, 0.025 ppm, 0.035 ppm, and 0.04 ppm . From these data, the NAFTA calculator gives 0.06 

ppm, which JMPR did not accept. JMPR typically goes higher than the NAFTA calculator 

where there are few samples and so established the 0.07 ppm MRL for mango. Harmonization 

with the established Codex MRL of 0.07 ppm is recommended for residues of difenoconazole 

in/on mango. 

The proposed tolerances should be revised to reflect the recommended tolerance levels and 

correct commodity definitions as specified in Table 6. 

Table 6. Tolerance Summary for Difenoconazole. 

Commodity Proposed Tolerance 

(ppm) 

Recommended Tolerance 

(ppm) 

Comments; 

Correct Commodity Definition

Mango, fruit 0.09 0.07 Mango 

Waxapple, fruit 1.5 1.5 Wax jambu 

References

DP#s: 172067 and 178394 

Subject: PP#2E4051. CGA-169374 (Difenoconazole, Dividend®) in Imported Wheat, 

Barley, and Rye Grain. First Food Use. CBTS#s 9029, 9895. 

From: R. Lascola 

To: J. Stone/C. Giles-Parker 

Dated: 10/26/92 

MRIDs: 42090001-42090004, 42090032-42090059, and 42303901 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 18 of 23 

DP#s: 203644 and 203645 

Subject: PP#2F4107. Difenoconazole (Dividend) in/on Wheat, and Animal RACs. 

Amendment of 5/18/94. CBTS# 13771 & 13772. 

From: G. Kramer 

To: C. Giles-Parker/J. Stone and A. Kocialski 

Dated: 6/16/94 

MRIDs: 43236501-43236503 

DP#: None 

Subject: HED Metabolism Committee Meeting of 7/14/94. PP#2F4107 & PP#2E4051. 

Difenoconazole (Dividend). 

From: G. Kramer 

To: HED Metabolism Committee 

Dated: 7/22/94 

MRIDs: None 

DP#: 327788 

Subject: Triazole-Based Metabolites: Guidance On Residue Chemistry Data Submissions. 

From: M. Doherty 

To: C. Giles-Parker 

Date: 4/25/06 

MRIDs: None 

DP#: 340379 

Subject: PP#6F7115; Difenoconazole. Petition for Establishment of Tolerances on 

Fruiting Vegetables, Pome Fruit, Sugar Beets, Tuberous and Corm Vegetables, 

and Imported Papaya. Summary of Analytical Chemistry and Residue Data. 

From: W. Wassell/M. Sahafeyan 

To: D. Rosenblatt/S. Brothers 

Dated: 8/9/07 

MRIDs: 46950215-46950237 

DP#: 371613 

Subject: Difenoconazole. Acute and Chronic Aggregate Dietary Exposure and Risk 

Assessments for the Section 3 Registration Request for Mango and Wax Apple. 

From: T. Morton 

To: Yan Donovan and Tony Kish 

Dated: 1/21/10 

MRIDs: None 

Attachments: 

International Residue Limit Status sheet 

Appendix I - Tolerance Assessment Calculations 

Template Version September 2005 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 19 of 23 

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 1-[2-[2-

chloro-4-(4-

chlorophenoxy)phenyl]-4-

methyl-1,3-dioxolan-2-

ylmethyl]-1H-1,2,4-

triazole 

Common Name: 

Difenoconazole 

X Proposed tolerances 

□ Reevaluated tolerance 

□ Other 

Date: 10/14/09 

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

□ No Codex proposal step 6 or above 

□ No Codex proposal step 6 or above for the crops 

requested 

Petition Number: PP#9E7573 

DP#: 366507 

Other Identifier: Decision No. 413927 

Residue definition (step 8/CXL): Difenoconazole Reviewer/Branch: B. Cropp-Kohlligian/RAB4 

Residue definition: Difenoconazole per se

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

Mango 0.07 Mango, fruit 0.09

 Waxapple, fruit 1.5

 

Limits for Canada Limits for Mexico 

□ No Limits 

X No Limits for the crops requested 

□ No Limits 

X No Limits for the crops requested 

Residue definition: Difenoconazole [1-[2-[-4-(4-

chlorophenoxy)-2-chlorophenyl]-4-methyl-1,3-

dioxolan-2-ylmethyl]-1H-1,2,4-triazole] 

Residue definition: Difenoconazole. Mexico defers to 

Codex MRLs or US tolerances for its export purposes. 

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

 

Notes/Special Instructions: S. Funk, 10/14/2009 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 20 of 23 

Appendix I. Tolerance Assessment Calculations.

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

Trial Data (SOP), along with the tolerance spreadsheet (August 2009 version), was used for 

calculating recommended tolerances. As specified in the SOP, since the datasets were small 

(≤15 samples) and reasonably lognormal, the upper bound estimate of the 95th percentile based 

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

percentile and the point estimate of the 99th percentile, and the minimum value was selected as 

the tolerance value. The rounding procedures specified in the SOP were also used. 

Mango 

The dataset used to establish a tolerance for difenoconazole on mango consisted of field trial 

data representing application rates of 0.335 lb ai/A (3 applications at 0.112 lb ai/A/application) 

with a 7-day PHI. The field trial application rates and PHIs are within 25% of the maximum 

label application rate and minimum label PHI, respectively. The residue values that were 

entered into the tolerance spreadsheet are provided in Table I-1. 

All field trial sample results for difenoconazole in/on mango were at or above the LLMV 

(LLMV = 0.01 ppm). The mango dataset was small (8 samples). Visual inspection of the 

lognormal probability plot (Figure I-1) and the results from the approximate Shapiro-Francia test 

statistic (Figure I-2) indicated that the mango dataset was reasonably lognormal. 

Using the tolerance spreadsheet, the recommended tolerance is 0.09 ppm for mango. 

Table I-1. Residue data used to calculate tolerance for residues of difenoconazole on mango.

Regulator: EPA 

Chemical: Difenoconazole 

Crop: Mango 

PHI: 7 days 

App. Rate: 0.335 lb ai/A 

Submitter: Syngenta Crop Protection, Inc. 

MRID Citation: MRID 47760602 

 Residues of Difenoconazole (ppm) 

 0.02 

 0.03 

 0.01 

 0.02 

 0.04 

 0.04 

 0.03 

 0.04 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 21 of 23 

Figure I-1. Lognormal probability plot of difenoconazole field trial data for mango. 

Lognormal Probability Plot

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

1.0000

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156

0.0078

y = 0.4796x - 3.6374

R2

 = 0.8464

Percentiles

Concentrations

EPA Difenoconazole Mango 7 days 0.335 lb ai/A Syngenta

Figure I-2. Tolerance spreadsheet summary of difenoconazole field trial data for mango. 

Regulator: EPA

Chemical: Difenoconazole

Crop: Mango

PHI: 7 days

App. Rate: 0.335 lb ai/A

Submitter: Syngenta

n: 8

min: 0.01

max: 0.04

median: 0.03

average: 0.03

95th Percentile 99th Percentile 99.9th Percentile

0.05 0.06 0.07

(0.07) (0.08) (--)

0.06 0.09 0.15

(0.15) (0.25) (--)

0.08

0.07

0.25

0.8464

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 22 of 23 

Waxapple 

The dataset used to establish a tolerance for difenoconazole on waxapple consisted of field trial 

data representing application rates of 2.74 lb ai/A (8 applications at 0.34 lb ai/A/application) 

with a 12-day PHI. The field trial application rates could not be compared to the maximum label 

application (insufficient Section B for the Taiwan label), and the PHIs were much lower (60%) 

than the reported minimum label PHI. The residue values for net-bagged fruit that were entered 

into the tolerance spreadsheet are provided in Table I-2. 

All field trial sample results for difenoconazole in/on waxapple were above the LLMV (LLMV = 

0.01 ppm). The waxapple dataset was small (6 samples). Visual inspection of the lognormal 

probability plot (Figure I-3) and the results from the approximate Shapiro-Francia test statistic 

(Figure I-4) indicated that the waxapple dataset was reasonably lognormal. 

Using the tolerance spreadsheet, the recommended tolerance is 1.5 ppm for waxapple. 

Table I-2. Residue data used to calculate tolerance for residues of difenoconazole on waxapple.

Regulator: EPA 

Chemical: Difenoconazole 

Crop: Waxapple (net-bagged) 

PHI: 12 days 

App. Rate: 2.74 lb ai/A 

Submitter: Syngenta Crop Protection, Inc. 

MRID Citation: MRID 47760601 

 Residues of Difenoconazole (ppm) 

 0.75 

 0.85 

 0.66 

 1.27 

 0.67 

 0.88 
Difenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507 

Page 23 of 23 

Figure I-3. Lognormal probability plot of difenoconazole field trial data for waxapple. 

Figure I-4. Tolerance spreadsheet summary of difenoconazole field trial data for waxapple. 

Regulator: EPA

Chemical: Difenoconazole

Crop: Waxapple (net-bagged)

PHI: 12 days

App. Rate: 2.74 lb ai/A

Submitter: Syngenta

n: 6

min: 0.66

max: 1.27

median: 0.80

average: 0.85

95th Percentile 99th Percentile 99.9th Percentile

1.3 1.4 1.6

(1.7) (2.0) (--)

1.3 1.5 1.8

(2.5) (3.0) (--)

2.0

1.6

7.0

0.8783

p-value > 0.05 : Do not reject lognormality assumption

Approximate

Shapiro-Francia

Normality Test

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD

Lognormal Probability Plot

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

2.0000

1.0000

0.5000

y = 0.2478x - 0.1925

R2

 = 0.8783

Percentiles

Concentrations

EPA Difenoconazole Waxapple (net-bagged) 12 days 2.74 lb ai/A Syngenta