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

  SEQ CHAPTER \h \r 1 Pyraclostrobin, or methyl
N-[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]-N-methoxyc
arbamate, belongs to the strobilurin class of fungicides.  Strobilurins
are synthetic 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

  SEQ CHAPTER \h \r 1 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.
   SEQ CHAPTER \h \r 1 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),
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 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-
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 .

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
Multiva™ 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 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	

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]-N-methoxyc
arbamate

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/cm3 	45118214

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-1
cm-1]): 2.5x104 at 205 nm; 2.4x104 at 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%).

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

™ 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]

Multiva™EC

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

Headline™ 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
Multiva™ 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

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.

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

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 (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	SampleMin.	Sample

Max.	LAFT2	HAFT2	Median	Mean	Std. Dev.

Sugarcane	0.78-0.81

(0.88-0.91)	13-14	Pyraclostro-bin	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	Pyraclostro-bin	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	Pyraclostro-bin	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	Pyraclostro-bin	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.

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)1	Processing Factor



	Pyraclostrobin	BF 500-32	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

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 r  SEQ CHAPTER \h \r 1 esidues 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. 

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)-1H-pyrazol-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

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

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 

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-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]methoxycarbam
ate, including the metabolite [2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-

yl]oxy]methyl]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.

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.

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؀Ĥ摧⿙Æ฀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

 	 

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.

Pyraclostrobin		D403449

Page   PAGE  1  of   NUMPAGES   9 

