Pyraclostrobin D403449

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

MEMORANDUM

Date: 04/16/2013

SUBJECT: Pyraclostrobin: Request for the Use on Sugarcane. Summary of Analytical 

Chemistry and Residue Data.

PC Code: 099100 DP Barcodes: 403449; ,403451; 403452; 403453; 

403454; 403456; 403462;

Decision No.: 465126 Registration Nos.: 7969-185; 7969-186; 7969-247; 

7969-258; 7969- 289; 7969-291

Petition Nos.: 2F8038 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical/Aggregate Case No.: N/A

TXR No.: N/A CAS No.: 175013-18-0

MRID No.: 48237401 40 CFR: 180.582

 

 

FROM: Stephen Funk, Senior Chemist

Risk Assessment Branch III (RAB III)

Health Effects Division (HED; 7509P)

THROUGH: Christine Olinger, Branch Chief

Risk Assessment Branch III (RAB III)

Health Effects Division (HED; 7509P)

TO: T. Kish/d. Schuler, RM# 22 

Fungicide Branch

Registration Division (RD; 7505P)

And

Barry O’Keefe, Senior Biologist

Risk Assessment Branch III (RAB III)

Health Effects Division (HED; 7509P)

Executive Summary

Pyraclostrobin, or methyl N-[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]-Nmethoxycarbamate, belongs to the strobilurin class of fungicides. Strobilurins are synthetic 
Pyraclostrobin D403449

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analogs of a natural antifungal substance which inhibits spore germination, mycelial growth, and 

sporulation of the fungi causing diseases such as fruit rot in strawberry, early leaf rot in peanuts, 

late blight in pistachios, rust diseases in soybeans, and pre- and post-fruit rot of pome and stone 

fruits. The fungicide is currently registered to BASF Corporation (BASF) for use on a variety of 

field, vegetable, fruit, and nut crops. It is formulated as water-dispersible granules (WDG) or an 

emulsifiable concentrate (EC) and is typically applied as foliar applications using ground or 

aerial equipment at maximum seasonal rates of 0.3-3.0 lb ai/A. The 20% WDG formulation is 

also registered for use as a seed treatment on some crops.

BASF is proposing a new use for pyraclostrobin on sugarcane. The proposed use is for up to 

four applications of an EC or SC formulation at 0.20 lb ai/acre with a seasonal maximum rate of 

0.80 lb ai/acre and a 14 day preharvest interval (PHI). There is an existing Section 18 tolerance 

for sugarcane.

BASF has proposed the establishment of a tolerance for the combined residues of the fungicide 

pyraclostrobin (carbamic acid, [2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-

yl]oxy]methyl]phenyl]methoxy-, methyl ester) and its desmethoxy metabolite methyl-N-[[[1-(4-

chlorophenyl) pyrazol-3-yl]oxy]o-tolyl] carbamate, expressed as parent compound, in or on the 

following raw agricultural commodity:

Sugarcane, cane........................................0.2 ppm

Tolerances have been established in 40 CFR §180.582 for residues of the fungicide 

pyraclostrobin, including its metabolites and degradates. Compliance with the tolerance levels is 

to be determined by measuring only the sum of pyraclostrobin (carbamic acid, [2-[[[1-(4-

chlorophenyl)-1H- pyrazol-3-yl]oxy]methyl]phenyl]methoxy-, methyl ester) and its desmethoxy

metabolite (methyl N-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl carbamate), 

calculated as the stoichiometric equivalent of pyraclostrobin . The established tolerances for 

plant food commodities range from 0.02 ppm in/on wheat grain to 29 ppm in/on leafy vegetables, 

except Brassica. Tolerances for livestock commodities are listed in 40 CFR §180.582 (a)(2) and 

are expressed in terms of the combined residues of the fungicide pyraclostrobin and its 

metabolites convertible to 1-(4-chlorophenyl)-1H-pyrazol-3-ol and 1-(4-chloro-2-

hydroxyphenyl)-1H-pyrazol-3-ol, expressed as parent compound. The established tolerances for 

livestock commodities range from 0.1 to 1.5 ppm; no tolerances are established for poultry

commodities.

HED (D278044, Metabolism Assessment Review Committee (MARC), 10/09/01) has 

determined that for purposes of tolerance and dietary risk assessments, the residues of concern in 

plant and rotational crop commodities include pyraclostrobin and desmethoxy metabolite (BF 

500-3). The residues of concern in livestock commodities include pyraclostrobin and its 

metabolites convertible to 1-(4-chlorophenyl)-1H-pyrazol-3-ol (BF 500-5) and 1-(4-chloro-2-

hydroxyphenyl)-1H-pyrazol-3-ol (BF 500-8).

There are adequate residue analytical methods for tolerance enforcement. The analytical 

methods for plant commodities are liquid chromatography with tandem mass spectrometry

(LC/MS/MS) and high pressure liquid chromatography with ultraviolet detection (HPLC/UV),
Pyraclostrobin D403449

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which both measure pyraclostrobin and its desmethoxy metabolite. The analytical methods for 

livestock commodities, gas chromatography with mass spectrometry (GC/MS) and LC/MS/MS,

convert pyraclostrobin and related metabolites to chlorophenylpyrazolol (BF 500-5) and 

hydroxylated chlorophenylpyrazolol (BF 500-8) in goats and chlorophenylpyrazolol (BF 500-5) 

and a hydroxylated chlorophenylpyrazolol isomer of BF 500-8 (BF 500-9) in poultry. 

Samples were analyzed for pyraclostrobin using BASF Analytical Method Number D9908

(Version 2), "Method for Determining BAS 500 F, BF 500-3 and BAS 510 F Residues in Plant 

Matrices using LC/MS/MS." The final chromatographic analysis of residues was determined by

LC/MS/MS. The lower limit of method validation (LLMV) in this study was 0.02 ppm for both 

pyraclostrobin and BF 500-3. The LC/MS/MS method used to determine residues of 

pyraclostrobin and BF 500-3 were adequately validated in conjunction with the field sample 

analyses. The average recovery of all pyraclostrobin and BF 500-3 fortifications was adequate. 

The method is adequate for data collection.

The requirements for multiresidue methods testing data are fulfilled. Pyraclostrobin was 

successfully evaluated through several of the FDA protocols (complete recovery through 

protocols D and E), while recovery of metabolite BF 500-3 was unsuccessful in all protocols.

Samples of sugarcane from field trials were stored frozen for up to 24.9 months prior to analysis.

Samples of sugarcane RAC, blackstrap molasses, and refined sugar from the processing study

were stored frozen for up to 17.0 months from collection to extraction Submitted freezer storage 

stability data indicate that residues of pyraclostrobin and BF 500-3 are stable in diverse 

representative crop matrices for up to 25 months. These data are adequate to support the storage 

conditions and durations of samples from the sugarcane field trials and processing studies.

Sugarcane molasses is a livestock feed item of regulatory interest, comprising up to 10% of the 

diet of dairy and beef cattle. Low concentration of pyraclostrobin in the processed commodity

from the proposed use will have no effect on the calculated livestock diet.

BASF has submitted field trial data for eight trials for pyraclostrobin sugarcane in the USA. At 

each trial location, the treated plots received four foliar directed or foliar broadcast applications 

of a 2.09 lb ai/gal emulsifiable concentrate (EC) formulation of pyraclostrobin (Headline®) 

during the vegetative or bloom stages of development at rates of 0.189-0.206 lb ai/A/application 

(0.21-0.23 kg ai/ha/application), for total seasonal rates of 0.78-0.81 lb ai/A (0.88-0.91 kg ai/ha). 

Retreatment intervals (RTIs) were 13-14 days. Applications were made using ground equipment 

in spray volumes of 15.54-27.15 gal/A of water (145-254 L/ha). A nonionic surfactant (NIS) was 

added to the spray mixture at each trial in the LA and TX trials; however, no adjuvant was used 

in the FL trials. Samples of sugarcane were harvested from trials at preharvest intervals (PHIs) of 

13-14 and 27-28 days. 

Residues (and per trial averages) of pyraclostrobin, of BF 500-3, and of combined pyraclostrobin 

and BF 500-3 in/on sugarcane harvested at a 13- to 14-day PHI were <0.02-0.1049 (<0.02-

0.099), <0.02-0.0267 (<0.02-0.027), and <0.04-<0.1249 (<0.040-<0.119) ppm, respectively. 

Following the same treatment at a 27- to 28-day PHI, residues of BF 500-3 in/on all sugarcane 

samples were <0.02 ppm, and residues (and per trial averages) of pyraclostrobin and of combined 
Pyraclostrobin D403449

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pyraclostrobin and BF 500-3 were <0.02-0.0866 (<0.020-0.068) and <0.04-<0.1066 (<0.040-

<0.088) ppm, respectively. 

A processing study was also conducted for sugarcane. At two trial locations (Trial IDs 08-FL32 

and 08-TX24), an additional plot received four foliar directed or foliar broadcast applications of 

the Headline®formulation of pyraclostrobin during the vegetative or bloom stages of 

development at rates of 0.977-1.04 lb ai/A/application (1.09-1.13 kg ai/ha/application), for total 

seasonal rates of 3.94-3.99 lb ai/A (4.42-4.47 kg ai/ha, 5x rate). Sugarcane was processed within 

21-27 days of harvest into blackstrap molasses and refined sugar using simulated commercial 

procedures. Concentration of pyraclostrobin and BF 500-3 did not occur.

Analytical reference standards for pyraclostrobin and its regulated metabolites are available at the 

EPA National Pesticide Standards Repository. 

Adequate confined, limited and extensive field rotational crop studies are available supporting 

the existing tolerances for indirect residues of pyraclostrobin in rotational crops. These data 

support the 14-day plant-back interval currently specified for crops without pyraclostrobin uses. 

No additional rotational crop data are required for purposes of this petition. 

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for pyraclostrobin and concludes that pending 

submission of a revised label there are no residue chemistry deficiencies that would preclude 

granting Section 3 registration for the requested crop commodity use of pyraclostrobin, or 

establishment of a tolerance for residues of pyraclostrobin. It is recommended that a tolerance be 

established for residues of the fungicide pyraclostrobin, including its metabolites and degradates, 

in or on sugarcane, cane at 0.2 ppm. Compliance with the tolerance levels is to be determined by

measuring only the sum of pyraclostrobin (carbamic acid, [2-[[[1-(4-chlorophenyl)-1H- pyrazol3-yl]oxy]methyl]phenyl]methoxy-, methyl ester) and its desmethoxy metabolite (methyl N-[[[1-

(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl carbamate), calculated as the 

stoichiometric equivalent of pyraclostrobin .

A human health risk assessment is forthcoming.

860.1200 Direction for Use

A revised label is required for EPA Reg.No. 7969-247 (12.0% EC, Multiva®). The proposed 

label has a maximum seasonal rate of 0.52 lb ai/acre. However, the directions state that no more 

than 80 ozs of MultivaTM should be applied per season, which is equivalent to 0.68 lb ai. The 80 

ozs is incorrect and must be changed to 62 ounces of product.

Background

Pyraclostrobin belongs to the strobilurin class of fungicides. Strobilurins are synthetic analogs of 

a natural antifungal substance which inhibits spore germination and mycelial growth and 

sporulation of the fungus on the leaf surface. The chemical structure and nomenclature of 
Pyraclostrobin D403449

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pyraclostrobin are presented in Table 1. The physicochemical properties of the technical grade of 

pyraclostrobin are presented in Table 2.

TABLE 1. Test Compound Nomenclature.

Compound

N

N

Cl

O

N O

H3C

O

OCH3

Common name Pyraclostrobin

Company experimental name BAS 500 F

IUPAC name methyl 2-[1-(4-chlorophenyl)pyrazol-3-yloxymethyl]-N-methoxycarbanilate

CAS name methyl N-[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]-Nmethoxycarbamate

CAS registry number 175013-18-0

End-use product (EP) Headline® EC Fungicide, EPA Reg. No. 7969-186.

TABLE 2. Physicochemical Properties of Technical Grade Pyraclostrobin.

Parameter Value References1 (MRID)

Melting point/range 63.7-65.2oC 45118213

pH Not applicable

Density 1.367 g/cm345118214

Water solubility at 20 oC 1.9 ± 0.17 mg/L (deionized water, pH 5.8) 45118233

Solvent solubility n-heptane (0.37 g/100mL); 2-propanol (3.0 

g/100mL); 1-octanol (2.42 g/100mL); olive oil 

(2.80 g/100m/L); methanol (10.08 g/100mL); 

>50 g/100mL in acetone, ethyl acetate , 

acetonitrile, dichloromethane and toluene.

45118228

Vapor pressure 2.6 x 10-10 hPa at 20 oC 45118214

Dissociation constant, pKa None (no dissociable moieties)

Octanol/water partition coefficient, 

Log(KOW) at room temperature

3.990 mean log Pow; Pow is 9772 45118215

UV/visible absorption spectrum The structural identity of BAS 500 F was 

confirmed by NMR and MS spectra. UV 

molecular extinction (e [1 mol-1cm-1]): 2.5x104

at 205 nm; 2.4x104at 275 nm.

1996/109552

1

Product Chemistry data were reviewed by the Registration Division (DP# 269848 and DP# 274191, 5/3/01, 5/15/01, and 

6/7/01, S. Malak). 

2 BASF Document Number.

860.1200 Directions for Use

Proposed supplemental labels were provided for end use products7969-186, 7969-

247, 7969-289, and 7969-291. Supplemental labels were also supplied for the 

technical products 7969-185 (98.0%) and 7969-258 (90.2%).
Pyraclostrobin D403449

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TABLE 3. Summaryof Proposed Use Patterns of Pyraclostrobin.

Applic. Timing, 

Type, and 

Equip.

Formulation

[EPA Reg.

No.]

Applic. 

Rate

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI

(days)

Use Directions and Limitations

Sugarcane

Foliar with 

ground 

equipment, aerial

equipment, or 

sprinkler 

irrigation1

23/6%

2.09 lb ai/gal

HeadlineTM

EC

7969-186

0.146-0.196 N/S 0.78 14

Apply at 14 – 28 day intervals with no 

more than 2 sequential applications 

before alternating to a labeled non 

Group 11 fungicide.

Foliar with 

ground 

equipment, aerial 

equipment, or 

sprinkler 

irrigation1

12.0% 

+ 7.4% 

metconazole

1.083 lb ai/gal

[0.67 lb 

metconazole

/gal]

MultivaTMEC

7969-247

0.10-0.13 4 0.52 14

Apply at 14 – 28 day intervals with no 

more than 2 sequential applications 

before alternating to a labeled non 

Group 11 or non Group 3 fungicide.

Do not apply more than 80 oz of 

Multiva per acre per season [0.68 lb 

ai/acre]..

Foliar with 

ground

equipment, aerial 

equipment, ,or 

sprinkler 

irrigation1

23.3%

2.08 lb ai/gal

HeadlineTM

SC

7969-289

0.195 N/S 0.78 14

Apply at 14 – 28 day intervals with no 

more than 2 sequential applications 

before alternating to a labeled non 

Group 11 fungicide.

Foliar with 

ground 

equipment, aerial 

equipment, or 

sprinkler 

irrigation1

13.64%

+5.14% 

metconazole

1.22 lb ai/gal

[0.46 lb 

metconazole 

/gal]

BAS 556 SC

7969-291

0.14-0.19 4 0.76 14

Apply at 14 – 28 day intervals with no 

more than 2 sequential applications 

before alternating to a labeled non 

Group 11 or non Group 3 fungicide.

Do not apply more than 80 oz of 

Multiva per acre per season [0.76 lb 

ai/acre]..

1 From approved existing master label. Not included in proposed supplemental label.

The label for 7969-247 (12.0% EC) has a maximum seasonal rate of 0.52 lb ai/acre. However, 

the directions state that no more than 80 oz of MultivaTM should be applied per season, which is 

equivalent to 0.68 lb ai. The 80 oz is incorrect and must be changed to 62 oz of product.

Conclusions: The submitted use directions are sufficient to allow for evaluation of the submitted 

residue data relative to the proposed use pattern. 

860.1300 Nature of the Residue - Plants
Pyraclostrobin D403449

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HED MARC, DP# 278044, L. Cheng, 10/9/01 

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

Adequate metabolism studies with pyraclostrobin on grapes, potatoes, and wheat have been 

reviewed (D269668, 11/28/01, L. Cheng) in conjunction with PP#0F06139. The results of these 

studies indicate that the metabolism of pyraclostrobin is similar in the three crops investigated. 

The HED Metabolism Assessment Review Committee (MARC) discussed the results of these 

studies on 9/20/01, and concluded that the nature of the residue in plants is understood. For the 

purpose of tolerance and risk assessment, the terminal residues of concern in plants consist of 

pyraclostrobin and its desmethoxy metabolite (BF 500-3).

860.1300 Nature of the Residue – Livestock

HED MARC, DP# 278044, L. Cheng, 10/9/01 

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

The nature of the residue in livestock is adequately understood based on acceptable ruminant and 

poultry metabolism studies. In goat, the major residues are pyraclostrobin and BF 500-3 in 

muscle and fat; pyraclostrobin, BF 500-3, and BF 500-5 and its sulfate conjugate in milk; 

pyraclostrobin, BF 500-3, and BF 500-5 and its sulfate conjugate, and hydroxylated desmethoxy

metabolite (500M67) in kidney; and metabolites hydrolyzed to BF 500-5 and its hydroxylated 

compound (BF 500-8) in liver. In poultry, the major residues are pyraclostrobin and BF 500-3 in 

eggs; pyraclostrobin, BF 500-3, and hydroxylated BF 500-3 (500M64) in fat; and the glucuronic 

acid conjugate of hydroxylated BF 500-3 (500M32) in liver. Radioactive residues were below 

detection in muscle. The main degradation reactions in livestock consist of demethoxylation, 

hydroxylation, and conjugation, and breaking of the ether bond.

HED has determined that for the tolerance and risk assessment, the residues of concern in 

livestock commodities consist of pyraclostrobin and its metabolites convertible to 1-(4-

chlorophenyl)-1H-pyrazol-3-ol (BF 500-5) and 1-(4-chloro-2-hydroxyphenyl)-1H-pyrazol-3-ol 

(BF 500-8).

860.1340 Residue Analytical Methods

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

PP#0F6139, DP# 269850, L. Cheng, 11/8/00

MRID: 48049201, W. Cutchin, in process

Enforcement: Two adequate methods are available for enforcement purposes for residues of 

pyraclostrobin and the metabolite BF 500-3 in/on plant commodities: an LC/MS/MS method 

(BASF Method D9908) and an HPLC/UV method (Method D9904). The validated method LOQ 

for both pyraclostrobin and BF 500-3 is 0.02 ppm in all tested plant matrices, for a combined 

LOQ of 0.04 ppm. Adequate independent method validation and radiovalidation data were 

submitted for both methods and forwarded to Analytical Chemistry Branch/Biological and 

Economic Analysis Division (ACB/BEAD) for a petition method validation.

Data Collection: Samples from field trial and processing studies were analyzed for 

pyraclostrobin and its metabolite BF 500-3 using BASF Analytical Method Number D9908, 

"Method for Determining BAS 500 F, BF 500-3 and BAS 510 F Residues in Plant Matrices 

using LC/MS/MS.” Briefly, residues were extracted from sugarcane with methanol:water:2 N 
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HCl (70:25:5, v:v:v) by Polytron homogenization. After centrifugation, an aliquot of the 

supernatant was removed and cleaned up by liquid/liquid partitioning using cyclohexane and 1N 

HCl saturated with NaCl. An aliquot of the cyclohexane phase was taken, evaporated to dryness, 

and re-dissolved in a buffered methanol:water (80:20, v:v, each containing 0.1% formic acid and 

4 mM ammonium formate) for analysis by LC/MS/MS. MS/MS detection using the positive 

ionization mode monitored ion transitions from m/z 388→194 for pyraclostrobin and m/z 

358→164 for BF 500-3.

The LLMV in this study was 0.02 ppm for each of pyraclostrobin and BF 500-3. Concurrent 

recoveries from fortifications of sugarcane at 0.02 and 20 ppm ranged from 76% to 110%. 

Concurrent recoveries from blackstrap molasses at the same fortifications ranged from 85 –

112%, and for refined sugar, 85 – 101% There were acceptable concurrent method recovery

data.

Conclusions: There are adequate residue analytical methods for tolerance enforcement and data 

collection.

860.1360 Multiresidue Methods

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

Pyraclostrobin was successfully evaluated through several of the FDA protocols, while recovery

of BF 500-3 was unsuccessful in all protocols. Pyraclostrobin was completely recovered through 

Protocol D (in grape) and E (in grape), and partially recovered through Protocol F (in peanut). 

Metabolite BF 500-3 had poor peak shape and inadequate sensitivity with Protocol C columns, 

and therefore was not further analyzed under Protocol D, E, and F. The results of the 

multiresidue testing for pyraclostrobin were forwarded to FDA on 1/4/02 for the purpose of 

updating the Pesticide Analytical Manual, Volume I (PAM I).

860.1380 Storage Stability

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

Samples of sugar cane from the field trials were stored frozen (<-17 °C) for up to 757 days 

(about 25 months). Samples of processed commodities were stored frozen (≤-12 °C) for up to 

518 days (17 months). Residues of pyraclostrobin and its metabolite BF 500-3 are stable under 

frozen storage conditions in/on representative crop commodities of grape juice, sugar beet tops 

and roots, tomatoes, and wheat grain and straw for up to 25 months, and peanut nutmeat and 

processed oil for up to 19 months.

Conclusions: These data are adequate to support the storage conditions and durations of samples 

from the sugarcane field trials and processing study.

860.1400 Water, Fish, and Irrigated Crops

This guideline requirement is not relevant to the current petitions as there are no aquatic uses 

being proposed for pyraclostrobin.

860.1460 Food Handling
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This guideline requirement is not relevant to the current petitions as there are no food-handling 

uses being proposed for pyraclostrobin.

860.1480 Meat, Milk, Poultry, and Eggs

Sugarcane blackstrap molasses is a carbohydrate concentrate (CC) feed item for dairy cattle and 

beef cattle and may comprise up to 10% of the diet of each. The processing factor for conversion 

of sugarcane to blackstrap molasses is 0.3X (S. Funk, 48237401.der2). Applying that factor to 

the HAFT for sugarcane (0.12 ppm, Table 4) yields a residue of 0.04 ppm on blackstrap 

molasses. The contribution to the diet is 0.12 X 10% / 75% DM = 0.02 ppm. The dietary 

exposure of cattle was most recently determined to be 6.1 ppm for beef cattle and 12.9 ppm for 

dairy cattle (D367409, 12/29/09, W. Cutchin). Carbohydrate concentrates (CC) contributed 2.56 

ppm to the dairy diet and 1.0 ppm to the beef cattle diet. These represent the maximum 

percentages allowed (80% CC for beef cattle and 45% for dairy cattle). Sugarcane blackstrap 

molasses was included in the calculation at a concentration of 0.4 ppm, based on the temporary

emergency tolerance. It contributed minimally (0.03 ppm) to the burden, and its contribution 

would now be less. Therefore, no significant changes to the dietary burden result from the 

present considerations. No changes to the existing livestock tolerances are indicated.

Sugarcane blackstrap molasses is not a poultry or swine feed item.

860.1500 Crop Field Trials

MRID: 48237401

BASF Corp. has submitted field trial data for pyraclostrobin on sugarcane. A total of 8 crop field 

trials on sugarcane were conducted in the United States during the 2008 growing season in North 

American Free Trade Agreement (NAFTA) Growing Zones 3 (FL, 3 trials), 4 (LA, 4 trials), and 

6 (TX). Examination of the field trial records indicates that one director supervised all three field 

trials in FL (all in the same city), and another director supervised all field trials in both LA (four 

in the same city) and the one trial approximately 600 miles distant in TX. Every crop field trial 

differed as to crop variety, and the four trials in LA involved three different soil types. Also, the 

geographic area in which sugarcane is cultivated in the continental USA is relatively small. The 

trials are considered independent (n = 8) for purposes of OSCPP 860.1500 data requirements. 

Each trial consisted of one untreated (control) plot and one treated plot. At each trial location, 

the treated plots received four foliar directed or foliar broadcast applications of a 2.09 lb ai/gal 

EC formulation of pyraclostrobin (Headline®) during the vegetative or bloom stages of 

development at rates of 0.189-0.206 lb ai/A/application (0.21-0.23 kg ai/ha/application), for total 

seasonal rates of 0.78-0.81 lb ai/A (0.88-0.91 kg ai/ha). RTIs were 13-14 days. Applications 

were made using ground equipment in spray volumes of 15.54-27.15 gal/A of water (145-254 

L/ha), containing 0.125-0.126% (v/v) of the NIS Silwet as an adjuvant in all trials except for 

those in FL, which used no adjuvant. At two trial locations (Trial IDs 08-FL32 and 08-TX24)

designed to produce samples for processing, an additional plot received four foliar directed or 

foliar broadcast applications of the Headline®formulation of pyraclostrobin (Headline®) at rates 

of 0.977-1.04 lb ai/A/application (1.09-1.13 kg ai/ha/application; 5x) beginning 56 days prior to 

harvest during the vegetative or bloom stages, with RTIs of 13 or 14 days. The total seasonal 
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(5x) rates were 3.94-3.99 lb ai/A (4.42-4.47 kg ai/ha). Applications were made using ground 

equipment, and the spray volumes were 21.65-22.32 gal/A of water (202-209 L/ha), containing 

0.125-0.128% (v/v) of the NIS Silwet as an adjuvant in the TX trial; no adjuvant was used in the 

FL trial. Samples of sugarcane were harvested from all trials at PHIs of 13-14 and 27-28 days. 

Samples of sugarcane were fortified with pyraclostrobin and BF 500-3 at 0.02 and 20 ppm.

The method was adequate for data collection based on acceptable concurrent recovery data. 

Recoveries were all within the acceptable range of 70-120%. The fortification levels used in 

concurrent method recovery were adequate to bracket expected residue levels. No residues of 

pyraclostrobin or its metabolite BF 500-3 equal to or above the LLMV were detected in any

control samples. 

Results are summarized in Table 4.

TABLE.4. Summary of Residue Data from Crop Field Trials with Pyraclostrobin.

Commodity Total 

Applic. Rate

(lb ai/A)

[kg ai/ha]

PHI 

(days)

Analyte Residue Levels1

(ppm)

n Sample

Min.

Sample

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Sugarcane 0.78-0.81

(0.88-0.91)

13-14

Pyraclostrobin 8 <0.02 0.1049 <0.02 0.099 0.058 <0.060 0.026

BF 500-3 8 <0.02 0.0267 <0.02 0.027 <0.02 <0.021 0.002

Combined 8 <0.04 <0.125 <0.040 <0.119 <0.076 <0.076 0.029

27-28

Pyraclostrobin 8 <0.02 0.0866 <0.020 0.068 0.043 <0.044 0.016

BF 500-3 8 <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 N/A

Combined 8 <0.04 <0.1066 <0.040 <0.088 <0.062 <0.061 0.017

Sugarcane

(for 

processing)

3.94-3.99

[4.42-4.47]

14

Pyraclostrobin 2 0.0238 0.2935 0.028 0.255 0.141 0.141 N/A

BF 500-3 2 <0.02 0.0253 <0.02 0.025 <0.022 <0.022 N/A

Combined 2 <0.044 0.319 <0.048 0.280 <0.164 <0.164 N/A

28

Pyraclostrobin 2 0.0203 0.38113

0.026 0.268 0.147 0.147 N/A

BF 500-3 2 <0.02 0.0405 <0.02 <0.030 <0.025 <0.025 N/A

Combined 2 <0.040 0.422 <0.046 <0.299 <0.172 <0.172 N/A

Conclusions: 

The number and geographic distribution of the trials are adequate. The analytical 

method was demonstrated to be acceptable via concurrent recoveries of fortified 

control samples. The intervals of frozen storage of samples are covered by

previous storage stability studies, and no corrections for loss of residue are 

needed. The trials were conducted according to the proposed label for the EC 

formulation (single and seasonal application rates, PHI). The results of the field 

trials are acceptable for estimation of a sugarcane tolerance and for dietary risk 

assessment purposes.
Pyraclostrobin D403449

Page 11 of 18

860.1520 Processed Food and Feed

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

MRID 48237401

A processing study was submitted for sugarcane. In a single sugarcane field trial 

conducted in North American Free Trade Agreement (NAFTA) Growing Zone 6 

(TX) during the 2008 growing season, a 2.09 lb ai/gal emulsifiable concentrate 

(EC) formulation of pyraclostrobin (Headline®) was applied to sugarcane as four 

broadcast foliar applications at rates of 0.977-0.993 lb ai/A/application (1.09-1.11 

kg ai/ha/application; reported 5x rate) beginning 53 days prior to harvest during 

the vegetative stage, with a retreatment interval (RTI) of 13 days. The total 

seasonal rate was 3.94 lb ai/A (4.42 kg ai/ha; 5x). 

Bulk samples of sugarcane were harvested 14 days after the last application. Sugarcane was 

processed within 21-27 days of harvest into blackstrap molasses and refined sugar using 

simulated commercial procedures. 

Samples of sugarcane cane and processed sugarcane commodities were analyzed for residues of 

pyraclostrobin and its metabolite BF 500-3 using a liquid chromatography method with tandem 

mass spectrometry detection (LC/MS/MS), Method D9908 (Version II). Samples of sugarcane 

RAC, blackstrap molasses, and refined sugar were fortified with pyraclostrobin and BF 500-3 at 

0.02 and 20 ppm. The method was adequate for data collection based on acceptable concurrent 

recovery data. Recoveries were all within the acceptable range of 70-120%. 

Results are summarized in Table 5. 

Table 5 Residue Data from Sugarcane Processing Study with Pyraclostrobin.

Sugarcane Commodity Total Rate

(lb ai/A)

[kg ai/A]

PHI 

(days)

Residues (ppm)1Processing 

Factor Pyraclostrobin BF 500-3

2 Combined2

Sugarcane RAC

3.94

[4.42] 14

0.232 0.033 0.265 --

Blackstrap molasses 0.057 <0.02 <0.077 <0.29x

Refined sugar <0.02 <0.02 <0.04 <0.15x

1 The petitioner used the lowest level of method validation (LLMV) of 0.02 ppm as the limit for reporting residues for both 

pyraclostrobin and its metabolite BF 500-3. For determining the combined residues, the LLMV was used for values reported as 

<LLMV.

2 Residues of metabolite BF 300-3 were reported in parent equivalents.

Conclusions:

The submitted sugarcane processing study is adequate. An acceptable method was used for 

quantitation of pyraclostrobin and BF 500-3 residues in sugarcane RAC and sugarcane processed 

commodities. Samples were stored frozen for intervals covered by the storage stability study.

Residues of pyraclostrobin and BF 500-3 did not concentrate in blackstrap molasses or refined 

sugar, relative to the concentration in the raw agricultural commodity (sugarcane). Therefore, 

tolerances are not necessary for these processed commodities.

860.1650 Submittal of Analytical Reference Standards
Pyraclostrobin D403449

Page 12 of 18

Analytical reference standards for pyraclostrobin and regulated metabolites (BF 500-3; BF 500-5; 

BF 500-8) are currently available in the EPA National Pesticide Standards Repository (e-mail 

correspondence with T. Cole, 01/14/2013). 

860.1850 Confined Accumulation in Rotational Crops

MARC, DP# 278044, L. Cheng, 10/9/01

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

An adequate confined rotational crop study was reviewed in PP#0F6139. The study showed that 

the metabolism of pyraclostrobin in rotated crops is similar but more extensive than that in 

primary crops. Pyraclostrobin undergoes demethoxylation to yield BF 500-3, followed by further 

degradation to medium polar and polar metabolites, and subsequent conjugation reactions and 

incorporation into natural products. The HED MARC has determined that the residues of 

concern in rotational crops consist of pyraclostrobin and metabolite BF 500-3.

860.1900 Field Accumulation in Rotational Crops

PP#0F6139, DP# 269668, L. Cheng, 11/28/01

A limited field rotational crop study was reviewed in PP#0F6139. The results indicate that 

residues of pyraclostrobin and its metabolite BF 500-3 were each less than the method LOQ 

(<0.02 ppm) in/on rotational crop matrices (radish, roots and tops; cabbage, with and without 

wrapper leaves; and wheat forage, hay, and grain) planted 14 days following the last of six 

sequential foliar applications to the primary crop, cucumbers, of the 2 lb/gal EC formulation at 

0.19 - 0.20 lb ai/A/application. Residues of pyraclostrobin in/on one sample of wheat straw from 

the CA test site were at the LOQ (0.02 ppm), but residues of pyraclostrobin in/on a replicate 

sample from the same plot were below the LOQ (0.012 ppm) for an average residue of <0.02 

ppm. Residues of metabolite BF 500-3 were nondetectable (<0.02 ppm) in/on all samples of 

wheat straw.

The registered pyraclostrobin end-use product labels presently specify a 14-day plantback 

interval restriction for all crops that are not registered. 

860.1550 Proposed Tolerances

For the use of pyraclostrobin on sugarcane a tolerance is required. A time-limited Section 18 

tolerance of 0.02 ppm exists (40 CFR §180.582(b). Based on evaluation of the sugarcane field 

trial data with the Organization for Economic Cooperation and Development (OECD) tolerance 

calculation procedure, a tolerance of 0.2 ppm is appropriate for sugarcane, cane (see Appendix I).

Codex and Canada have not established MRLs for pyraclostrobin on sugarcane. Therefore, there 

is no issue of harmonization.

Pyraclostrobin residues did not concentrate in sugarcane molasses and sugarcane refined sugar. 

Therefore these commodities are covered by the tolerance for the raw agricultural commodity, 

sugarcane, cane.

The recommended tolerances for sugarcane commodities is presented in Table 6.
Pyraclostrobin D403449

Page 13 of 18

Table 6. Tolerance Summary for Pyraclostrobin.

Commodity Proposed/Existing

Tolerance (ppm)

Recommended/ 

Harmonized

Tolerance (ppm)

Comments; Correct Commodity 

Definition

40 CFR §180.582(a) It is recommended that a tolerance be established for residues of the fungicide pyraclostrobin, 

including its metabolites and degradates, as indicated below . Compliance with the tolerance levels is to be 

determined by measuring only the sum of pyraclostrobin (carbamic acid, [2-[[[1-(4-chlorophenyl)-1H- pyrazol-3-

yl]oxy]methyl]phenyl]methoxy-, methyl ester) and its desmethoxy metabolite (methyl N-[[[1-(4-chlorophenyl)-1Hpyrazol-3-yl]oxy]methyl]phenyl carbamate), calculated as the stoichiometric equivalent of pyraclostrobin 

Sugarcane, cane 0.2 0.20 -

40 CFR §180.582(b) Section 18 emergency exemptions

Sugarcane, cane 0.02 Revoke Replaced with new tolerance in 

(a)

Sugarcane, molasses 0.40 Revoke Replaced with new tolerance in 

(a) for sugarcane, cane

References

DP#s: 367409

Subject: Pyraclostrobin. Petition for New Uses and Tolerances on Alfalfa. Summary of 

Analytical Chemistry and Residue Data.

From: W. Cutchin

To: T. Kish/J. Bazuin

Dated: 10/19/09

MRIDs: 47584401

DP#s: 281042, 286732, 287729, 288459, 290342, 290343, 290369, 292440, 293088, 

293684, 295893, 298178

Subject: Pyraclostrobin. PP#3F06581, 2F06431, 2E6473, 3E6548, 3E6553, 3E6774, and 

2F06139. Petitions for the establishment of permanent tolerances to allow uses on 

corn (field, sweet, and pop), hops, mint, pome fruits, edible-podded legume 

vegetables, succulent peas, sunflower, Brassica leafy greens, soybeans, succulent 

beans, broccoli, cabbage, lettuce (head and leaf), spinach, celery, turnip greens, 

and the import commodities mango and papaya. Application for amended Section 

3 registration for citrus (reduced PHI). Petitioner’s response to data deficiencies 

identified in PP#0F06139 regarding storage stability data, dried shelled peas and 

beans (reduced PHI), and uses on dry and succulent peas. Summary of Analytical 

Chemistry and Residue Data.

From: L. Cheng

To: C. Giles-Parker/J. Bazuin

Dated: 7/26/04

MRIDs: 45596211, 45623406, 45623407, 45623408, 45623410, 45645801, 45645802, 

45645803, 45645804, 45702901, 45765401, 45832001, 45858801, 45858802, 

45903601, 45903602, 46033901-04, 46084401-04, 46109101, 46109102
Pyraclostrobin D403449

Page 14 of 18

DP#s: 269668, 272771, 272789, 274095, 274192, 274471, 274957, 275843, and 278429

Subject: PP#0F06139. Pyraclostrobin on Various Crops: Bananas (import), Barley, 

Berries, Bulb Vegetables, Citrus Fruits, Cucurbit Vegetables, Dried Shelled Pea & 

Bean (except Soybean), Fruiting Vegetables, Grapes, Grass, Peanut, Pistachio, 

Root Vegetables (except Sugar Beet), Rye, Snap Beans, Stone Fruits, Strawberry, 

Sugar Beet, Tree Nuts, Tuberous and Corm Vegetables, and Wheat. Review of 

Analytical Methods and Residue Data. 

From: L. Cheng

To: C. Giles-Parker/J. Bazuin

Dated: 11/28/01

MRIDs: 45118428-451184-37, 45118501-45118512, 45118514-45118537, 45118601-

45118625, 45160501, 45272801, 45274901, 45321101, 45367501, 45399401, and 

45429901

DP#: 278044

Subject: PP# 0F06139. PC Code 099100. Pyraclostrobin. Outcome of the HED 

Metabolism Assessment Review Committee (MARC) Meeting Held on 

September 20, 2001.

From: L. Cheng

To: Y. Donovan

Dated: 10/09/01

MRIDs: None

DP#: 269850

Subject: PP# 0F06139. Pyraclostrobin (BAS 500F) in or on Various Crops. Request for 

Tolerance Method Validation (TMV) Trial.

From: L. Cheng

To: F. D. Griffith, Jr.

Dated: 11/8/00

MRIDs: 45118505, 45118504, 45118509, 45118510, 45118501, 45118503, 45118507, 

45118514
Pyraclostrobin D403449

Page 15 of 18

DP#: 281042, 286732, 287729, 288459, 290342, 290343, 290369, 292440, 293088, 

293684, 295893, 298178

Subject: Pyraclostrobin. PP#3F06581, 2F06431, 2E6473, 3E6548, 3E6553, 3E6774, and 

2F06139. Petitions for the establishment of permanent tolerances to allow uses on 

corn (field, sweet, and pop), hops, mint, pome fruits, edible-podded legume 

vegetables, succulent peas, sunflower, Brassica leafy greens, soybeans, succulent 

beans, broccoli, cabbage, lettuce (head and leaf), spinach, celery, turnip greens, 

and the import commodities mango and papaya. Application for amended Section 

3 registration for citrus (reduced PHI). Petitioner’s response to data deficiencies 

identified in PP#0F06139 regarding storage stability data, dried shelled peas and 

beans (reduced PHI), and uses on dry and succulent peas. Summary of Analytical 

Chemistry and Residue Data.

From: L. Cheng

To: Cynthia Giles-Parker

Dated: 7/26/04

MRIDs: 45596211, 45623406, 45623407, 45623408, 45623410, 45645801, 45645802, 45645803, 

45645804, 45702901, 45765401, 45832001, 45858801, 45858802, 45903601, 45903602, 

46033901-04, 46084401-04, 46109101, 46109102 
Pyraclostrobin D403449

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International Residue Limits

Pyraclostrobin (099100; 01/31/2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.582. Plants: Tolerances are 

established for residues of the fungicide 

pyraclostrobin, including its metabolites and 

degradates. Compliance with the tolerance levels 

is to be determined by measuring on the sum of 

pyraclostrobin (carbamic acid, [2-[[[1-(4-

chlorophenyl)-1H- pyrazol-3-

yl]oxy]methyl]phenyl]methoxy-, methyl ester) and 

its desmethoxy metabolite (methyl N-[[[1-(4-

chlorophenyl)-1H-pyrazol-3-

yl]oxy]methyl]phenyl carbamate), calculated as 

the stoichiometric equivalent of pyraclostrobin

methyl [2-

[[[1-(4-

chlorophen

yl)-1Hpyrazol-3-

yl]oxy]met

hyl]phenyl]

methoxycar

bamate, 

including 

the 

metabolite 

[2-[[[1-(4-

chlorophen

yl)-1Hpyrazol-3-

yl]oxy]met

hyl]phenyl]

carbamate

- Pyraclostrobin. Residue is NOT fat soluble.

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

US Canada Mexico2 Codex3

Sugarcane, cane 0.2 None None

1

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

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.
Pyraclostrobin D403449

Page 17 of 18

Appendix I: Determination of Tolerance for Pyraclostrobin in/on Sugarcane and Its 

Processed Fractions

The Organization of Economic Cooperation and Development statistical procedure was used to 

calculate a tolerance estimate for sugarcane. The estimate agreed with the proposal of BASF.

Pyraclostrobin

Sugarcane

USA

0.80 lb ai/A, PHI 14 day

Total number of data (n) 8

Percentage of censored data 25%

Number of non-censored data 6

Lowest residue 0.040

Highest residue 0.119

Median residue 0.076

Mean 0.076

Standard deviation (SD) 0.029

Correction factor for censoring (CF) 0.833

Proposed MRL estimate

- Highest residue 0.119

- Mean + 4 SD 0.191

- CF x 3 Mean 0.190

Unrounded MRL 0.191

Rounded MRL 0.2

Residues (mg/kg) n

< 0.04 2

0.068 1

0.073 1

0.078 1

0.079 1

0.112 1

0.119 1

Pyraclostrobin

Sugarcane

USA

0.80 lb ai/A, 28 day
Pyraclostrobin D403449

Page 18 of 18

Total number of data (n) 8

Percentage of censored data 25%

Number of non-censored data 6

Lowest residue 0.040

Highest residue 0.088

Median residue 0.062

Mean 0.061

Standard deviation (SD) 0.017

Correction factor for censoring (CF) 0.833

Proposed MRL estimate

- Highest residue 0.088

- Mean + 4 SD 0.131

- CF x 3 Mean 0.153

Unrounded MRL 0.153

Rounded MRL 0.15

Residues (mg/kg) n

< 0.04 2

0.05 1

0.06 1

0.063 1

0.074 1

0.076 1

0.088 1

Processed Commodities

Pyraclostrobin and BF 500-3 declined in concentration from the raw agricultural commodity

(RAC) to refined sugar and blackstrap molasses processed products. Therefore, the tolerance for 

sugarcane will cover the processed commodities. No separate tolerances are needed.