Page 1 of 23 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.docPage 2 of 23 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

Page 3 of 23 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 c ontaining 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 toleran ces for tissues, milk, and egg range 0.05-0.20 ppm. Time-limited tolerances, expressed in terms of difenoconazole per se , are established underDifenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507

Page 4 of 23 §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

Page 5 of 23 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 cr op 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 da ta 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 requirement s 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 fo r 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

Page 6 of 23 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 tolera nce. 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 aDifenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507

Page 7 of 23 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

Page 8 of 23 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

Cl N N

N

CH 3 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 Cl OH

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/cm 3 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, pK a Reported as <0 in MRID 42090003 which wa s previously reviewed in DP#s 172067 and 178394; however, questions have arisen c oncerning this value. Re-examination of MRID 42090003 found that the product chemistr y data study to support the reported dissociation constant for the technical grad e of difenoconazole was not included. New data are expected. Octanol/water partition coefficient, Log(K O W ) 4.2 at 25 oC DP#s 172067 and 178394, 10/26/92, R. LascolaDifenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507

Page 9 of 23 Table 2. Physicochemical Properties of Difenoconazole.
Parameter Value Reference UV/visible absorption spectrum λ max 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 so luble concentrate formulation containi ng 12.5% w/v difenoconazole and 20% w/v

azoxystrobin.

Table 3b. Summary of Proposed Di rections 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 dilution 1 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, th e use rate on waxapple could not be determined from the Taiwan use pattern as summarized in Section B; only a concentration (dilution) levelDifenoconazole Summary of Analytical Chemistry and Residue Data DP#: 366507

Page 10 of 23 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

Page 11 of 23 860.1340 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 ali quot 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 hydr oxide 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

Page 12 of 23 860.1360 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-K ohlligian 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, R ugged, 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 ava ilable 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 Dura tions 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 Dura tions 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. HAFT 1 Median Mean Std. Dev. Mango (Brazil use = 375 g ai/ha (0.335 lb ai/A) total application rate, 7-day PHI) Mango 2 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 patt ern information is required, 30-day PHI) Waxapple, paper-bagged fruit 3 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, cons istent with the food portion of mango fruits to be analyzed according to PAM Vol. I, Section 102, the residue results were calculated and reporte d as difenoconazole in/on whole fruit. Difenoconazole residues in/on whole fruits we re 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.

MangoDifenoconazole 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 applica tions 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 co llected 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.Re v03). 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 exampl e 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 areDifenoconazole 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-beari ng 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 (8 th ) 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 “b agged” 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 lbDifenoconazole 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 pro cessed food and feed are not relevant to this tolerance petition.

860.1650 Submittal of Analytical Reference Standards

Analytical standards for difenoconazole (e xpiration 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 forDifenoconazole 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 42303901Difenoconazole 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 Chroni c 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 2005Difenoconazole 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]-1 H -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, 10/14/2009Difenoconazole 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 tol erance 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
0.04Difenoconazole 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**

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

0.5000

0.2500

0.1250

0.0625

0.0313

0.0156

0.0078 y = 0.4796x - 3.6374

R 2 = 0.8464

**Percentiles Concentrations**  **EPA Difenoconazole Mango 7 days 0.335 lb ai/A Syngenta**

Figure I-2. Tolerance spreadsh eet 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 tol erance 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
0.88Difenoconazole 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 spreadsh eet summary of difenoconazole field trial data for waxapple.

**Regulator:** EPA

**Chemical:** Difenoconazole
**Crop:** Waxapple (net-bagged)

**PHI:** 12 days

**A pp. Rate:**  2.74 lb ai/A
**Submitter:** Syngenta

**n:** 6

**m in:**  0.66

**m ax:**  1.27

**m edian:**  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 **A pproximate**  **Shapiro-Francia**

**N ormality Test** 

**EU Method I**

**N ormal** 

**UCLMedian95th**

**95/99 Rule**

**EU Method II**
**Distribution-Free**

**M ean+3SD**  **Lognormal Probability Plot**

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 2.0000

1.0000

0.5000 y = 0.2478x - 0.1925

R 2 = 0.8783

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