Pyraclostrobin Human Health Risk Assessment DP#: 378282

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OF FICE OF CH[ MICAL SAnTI'

A:"D POLLl 'TI O" PR[\,}:NTIO:"

MEMORANDUM

Date: 5/27/10

SUBJECT: Pyraclostrobin. Human Health Risk Assessment for the Decrease in Application

Volume and Increase in Soybean Forage and Hay Tolerances.

PC Code: 099100

Decision No.: 416999

Petition Nos.: 9F7569

Risk Assessment Ty pe: N/A

TXR No.: N/A

MRlD No.: 47774701-02

DP Barcode: 378282

Registration No.: 7969-186, 7969-289

Regulatory Act ion: Section 3 Registration

Case No.: N/A

CAS No.: 175013-18-0

40 C FR: 180.582

Ver.Apr.08

FROM: W. Cutchin, Acting Senior Branch Scientist . \.:..-Il t' J", { (if , l-: ,J

Alternative Risk Integration and Assessment (ARIA) Team

Risk Integration, Minor Use and Emergency Response Branch (RIMUERB)

Registration Division (RD; 7505P)

THROUGH: P. Deschamp, Branch Chief

Risk Assessment Branch III(RAB I

Health Effects Division (HED; 75 9

TO: T. KishiS. Hill, RM# 22'/

Fungicide Branch

RD (7505P)

ARIAIRIMUERB of RD of the Office of Pesticide Programs (OPP) is charged with estimating

the risk to human health from expo sure to pesticides. RD of OPP has requested that ARIA

evaluate hazard and expo sure data and conduct dietary, occupational, residential and aggregate

exposure assessments, as needed, to estimate the risk to human health that will result from

proposed and currently registered uses ofthe active ingredient pyraclostrobin.

The overall risk assessment, dietary risk assessment, and residue chemistry assessment were

provided by W. Cutchin.

Page I of 3
Pyraclostrobin Human Health Risk Assessment DP#: 378282

This document will only address the differences in the human health risk assessment from the

last assessment. The remainder of the original assessment remains unchanged (PP# 9F7528, OP

Num.: 362855, W. Cutchin, 1111 8/09).

Executive Summary

BASF requests the increase in tolerances for the combined residues ofthe fungicide

pyraclostrobin (carbamic acid, [2-[[[ I-(4-chlorophenyl)-1H- pyrazol-Syl]oxyJmethyl]phenyl]methoxy-, methyl ester) and its desmethoxy metabolite (methyl-N-[[[I-(4-

chlorophenyl)pyrazol-3-yl]oxy]-0-tolyl] carbamate), expressed as parent compound, inion the

following commodities:

Soybean, forage 11.0 ppm

Soybean, hay 14.0 ppm

Concurrently, BASF wishes to amend the registration of Headline® Fungicide (EPA Reg.

No. 7969-186) and Hcadline® SC Fungicide (EPA Reg. No. 7969-1289) to permit aerial

application at spray volumes down to 1 gallon per acre (GPA). Both Headline®, an EC

fonn ulation., and Headline® SC. a soluble concentrate formulation, contain 23.6% ai (2.09

Ib ai/gal) of pyraclostrobin. The proposed use is two applications at the maximum seasonal

rate of 0.2 Ib ai/A. The application may be made using ground or aerial equipment. The

proposed preharvest intervals (PHI) range to the beginning of flowering stage (25%) at 21

days.

Dietary (Food & Drinking Water) Exposure Assessment

ARIA has determined that the residue chemistry database is adequate to support the proposed

change in use pattern and increases in the soybean forage and hay tolerances. Soybean forage

and hay are not human food items, and the increases in hay and forage tolerances do not require

an increase in existing meat, milk. poultry and egg tolerances (PP# 9F7590, OP Num.: 37 1252,

w.Cutchin, 5/26/l0). Environmental Fate and Effects Division's (EFED) previous drinking

water assessment was based on the existing registered use of aerial application on turf and

ornamentals representing the highest application rate at 0.5 Ibs ai/acre with 6 maximum seasonal

applications at 14 day intervals. EFEO believed that the aerial use of pyraclostrobin on turf and

ornamentals would pose the upper-bound concentrations in surface and ground water since spray

drift increases and application efficiency decreases in an aerial application technique (DP Num:

362852, R. Miller; 10114/09). Therefore, the proposed usc on soybeans wil l not result io a higher

exposure to pyraclostrobin in drinking water. Since there is no increase in dietary (food +

drinking water) exposure to pyraclostrobin, a reassessment ofthe last dietary risk analysis (PP#

9F7528, DP Num.: 369379, W. Cutchin, 10/30/09) is not required.

Residential Exposure

No new residential uses of pp-ac1ostrobin are proposed in this petition. A product containing

pyraclostrobin (i.e., Insignia) is registered for application to residential turf grass and

recreational sites and was included in the last human health risk assessment.

Page2 0f 3
Pyrac1ostJob in

Aggregate Risk

Human Health Risk Assessment DP#; 378282

In accordance with the FQPA. ARIA must consider and aggregate (add) pesticide exposures and

risks from three major sources : food. drinking water, and residential exposures. Since there are

no changes in the expected exposures from the three major sources, there is no change in the

human health risk assessment for children and adults, which was found not to reach a level of

concern to the Agency (PP# 9F7528, DP Num.: 362855, W. Cutchin, 11/18/09).

Occupational Exposure

The previous occupational risk assessment considered exposure to workers from ground and

aerial foliar applications of pyraclostrobin using more applications and at a higher total

application rate than the proposed uses. Occupational pesticide handlers may experience shortand intermediate-term exposure to pyraclostrobin. The expo sure for mixer/loaders workers was

determined as the worst-case scenario. Dermal exposure risks were determined to not be of

concern to the Agency provided mixer/loaders use protective gloves as specified on the product

label. Inhalation exposure risks were also determined to not be of concern to the Agency if

mixer/loaders support approximately 600 acres treated per day or if they use a dust/mist filtering

respirator while supporting aerial applications of 1200 A treated/day. It is also possible for

agricultural workers to have post-application exposure to pesticide residues during the course of

typical agricultural activi ties. The most conservative estimate (i.e., highe st exposure/risk) of

post-application exposure resulted in exposure risks that did not exceed the Agency's level of

concern (DP Num: 366927, M. Dow, 7/23/09).

Since the previous occupational risk assessment was conducted with a total application rate

higher than the proposed uses on soybeans and exposure risks did not exceed the Agency's level

of concern, the occupational risk from the proposed uses will also not exceed the Agency's level

of concern .

Recommendation

There areno human health considerations that would preclude granting the reque sted uses of

pyraclostrobin on soybean. ARIA recommends for increases in the following tolerance s:

Soybean, forage II ppm

Soybean, hay 14 ppm

Note to PM: It is recommended that the tolerance expression for 40 CFR § 180.474(aXI ) be

changed to: "Tolerances areestablished for residues of the fungicide pyraclostrobin, including

its metabolites and degradates, in or on the commodities in the table below. Compliance with the

tolerance levels specified below 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-[[[ I-(4-chloropheny1)-lH-pyrazol-3-

yl]oxy]methyl]phenylcarbamate), calculated as the stoichiometric equivalent of pyraclostrobin, in

or on the commodity."

Page 3 of3
Pyraclostrobin Summary ofAnalytical Chem istry and Residue Data DP#: 37 1252

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

ornce OF O!UIICAL SAFETl·

A:'IiD POLLL'T10S PRE\"E:\TlO:'li

TO:

FROM:

PC Code: 099100

Incision No.: 416999

Petition Nos.: 9F7590

Risk Assessment Type: N/A

TXR No.: N/A

Y1RID No.: 47774701.{}2

MEMORANDUM

Date: 5/26/10

SUBJECT: Pyraclostrobin: Petition for the Decrease in Application Volume and Increase in

Soybean Forage and Hay Tolerances. Summary of Analytical Chemistry and

Residue Data.

DP Ba rcode: 37125 2

Registration !IIo.: 7969.\ 86, 7969·289

Regulatory Action: Section 3 Registration

Case :"'"0.: N/A

CAS No.: 175013-18 -0

40 e FR: 180.582

/"i:-L' VeT.Apr.08

, -' 1. ( / ' : 14 -- 'lc W. Cutchin. Acting Senior Branch Scientist / . -(- tL- ..... .

Alternative Risk Integration and Assessment (ARIA) Team

Risk Integration, Minor Use and Emergency Response Branch (RIMUERB)

Registration Division (RD; 7505P)

THROUGH: L Cheng, Ph.D,. Senior Chemist (J1lf)fJ t- ~f- Risk Assessment Branch III (RABII {Yt4

Health Effects Division (HED; 7509

T. KishfS. Hill. RM# 22/

Fungicide Branch

RD (7505P)

Action Requested

The registrant notified the Agency that over-tolerance residues have been found in soybean

forage and hay samples while generating bridging data at 3 locations (in a 2008 study) to support

reducing the application spray volume.

Executive Summary

BASF requests the increase in tolerances for the combined residues ofthe fungicide

Page I of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 371252

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

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

chlorophenyl)pyrazol-3-yl]oxy]-0-tolyl] carbamate), expressed as parent compound, inion the

following commodities:

Soybean, forage II .O ppm

Soybean, hay 14.0 ppm

Concurrently, BASF wishes to amend the registration of Headline® Fungicide (EPA Reg.

No. 7969-186) and Headline® SC Fungicide (EPA Reg. No. 7969-1289) to permit aerial

application at spray volumes down to 1 gallon per acre (GPA). Both Headline®, an EC

formulation, and Headline® SC, a soluble concentrate formulation, contain 23.6% ai (2.09

lb ai/gal) of pyraclostrob in. The proposed use is two application at the maximum seasonal

rate of 0.2 lb ai/A. The application may be made using ground or aerial equipment. The

proposed preharvest intervals (PHI) range to the beginning of flowering stage (25%).

The over-tolerance residues had been discussed in a ChemSAC meeting. Residue data in soybean

forage and hay showed comparable residues of parent and its metabolite when the fungicide

(BAS 500 00 F Fungicide) was applied, at the label rate, in sprays applied at 20 gallons per acre

(GPA), 2 GPA, or 1 GPA using a ground application device . According to the registrant, the trial

parameters used in these bridging studies were similar to those conducted to obtain the original

registration on soybean (in a 2002 study).

ChemSAC (5/13/09) noted that the formulation (20% BAS 500 F WG) used in the original field

trials also contained another active ingredient that may raise residue concentrations of

pyraclostrobin, as well as a "non-silicone spray adjuvant," at an unspecified concentration. The

2008 trials were described as containing 0.5 ptiA ofa crop oil concentrate. ChemSAC

determined that provided that there are insignificant differences in the type of adjuvants used,

and in the concentrations of these adjuvants in the sprays, between the 2002 and 2008 study, no

field trials in addition to the 3 bridging studies are needed. The SAC also concluded that new

soybean forage and hay data can be combined with the original data to derive new tolerances for

these 2 soybean commodities; while the new seed data do not support an increase in the seed

tolerance. The SAC also recommended that the registrant provide additional information to

support the assumption that the adjuvant is not affecting these results. The SAC further

concluded that the spray volume by ground applications is not a factor that affects residue levels

in soybean seed, forage, and hay.

Pyraclostrobin [carbamic acid, [2-[[[1-(1-(4-chlorophenyl)-IH-pyrazol-3-yl] oxy] methyl]

phenyl] methoxy-, methyl ester] belongs to the strobilurin class offungicides. 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 pestachios, rust diseases in soybeans, 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 ailA. The 20% WDG

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

Page 2 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 371252

Pyraclostrobin tolerances have been established in 40 CFR §180.582. To lerances for plant

commodities are listed in 40 CFR §180.582 (a)(I) and are expressed in terms of the combined

residues ofthe fungi cide pyraclostrobin (carbam ic acid, [2-[[[ 1-(4-chl orophenyl)-IH- pyrazol-S.

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

chlorophenyl)-IH-pyrazol-3-yl]oxy]methyl]phenyl carbamate), expressed as parent compound.

The established tolerance s for plant 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 ex pressed in

terms ofthe combined residues ofthe fungicide pyraclostrobin and its metabolites convertible to

1-(4-chlorophenyl)- lH-pyrazol-3-o1and 1-(4-chloro-2- hydro xyphenyl)- 1H-pyrazol-3-01,

expressed as parent compo und. The established tolerances for livestock commodities range from

0.1 to 1.5 ppm; no tolerances are established for poultry commodities.

The HED Metabolism Assessment Review Committee (MA RC) memo has determined that for

purposes oftolerance and dietary risk ass essments. the residues of concern in plant and rotational

crop commodities include pyraclostrobin and metabolite BF 500 -3. The residues of concern in

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

chlorophenylj-lH-pyrazol-j-ol (BF 500-5) and 1-(4-chloro-2-hydroxyphenyl)- IH-pyrazol-3-01

(BF 500-8).

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

methods for plant commodities are liquid chromatography with tandem mass spectroscopyl mass

spectroscopy detector (LCIMSIMS) and high pressure liquid chromatography with ultraviolet

detector (HPLCIUV), which both measure pyraclostrobin and its desmethoxy metabolite . The

analytical methods for live stock commodities, gas chromatography with mass spectroscopy

detector (GCIMS) and LC/MSIMS, convert pyraclostrobin and related metabolites to

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

and chlorophenylpyrazolol (BF 500-5) and hydroxylated chlorophenylpyrazolol (BF 500-9) in

poultry. HED concluded that these methods are suitable as enforcement methods.

Samples ofraw agricultural and processed commodities from the current petitions were analyzed

for pyrac lostrobin residues of concern using an adequate LCIMSIMS method (BASF Method

D9908, ver. II), which is similar to the proposed enforcement method. The method was

adequately validated in conjunction with the field trial anal yses. Total residues of pyraclostrobin

and BF 500·3 are expressed as pyraclostrobin equivalents. For each analyte, the validated

method limit of quantitation (LOQ) is 0.02 ppm. 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 (co mplete recovery through

protocols D and E), whil e recovery ofmetabolite BF 500-3 was unsuccessful in all protocols.

There are adequate storage stability data from previous pyraclostrobin petitions. There are no

correc tions which need to be applied since pyraclostrobin residues ofconcern were found to be

reasonably stable over a wide range of commodities under frozen storage conditions for 19-25

Page 3 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#; 371252

months. These data may be translated in the current petition to validate sample storage

conditions and durations.

Adequate cattle and poultry feeding studies are available to support the livestock dietary burdens

resulting from the proposed uses. The only soybean commodities which will have higher

tolerances than those used in the last estimate of livestock diets are soybean forage and hay.

Since soybean forage and hay are considered feedstuffs only for dairy cattle , there are no changes

in the previous diets for beef cattle, poultry and swine, and therefore no changes in the associated

livestock tolerances are required. The current pyraclostrobin tolerances for livestock

commodities were established based on results from the dairy cattle feeding study and the

Agency's previously estimated dietary burdens for pyraclostrobin residues. Based on the updated

dairy cattle dietary exposure levels and the residue data from the dairy cattle feeding study, the

existing pyraclostrobin tolerance for milk at 0.1 ppm is adequate and will not need to be changed

as a result ofthe proposed uses in this petition.

The petitioner has provided adequate bridgin g residue data reflecting the maximum proposed use

pattern ofpyraclostrobin inion soybean forage and hay. The combined residues ofpyraclostrobin

and its metabolite BF 500-3 did not exceed the proposed tolerance levels of 11 .0 ppm and 14.0

inion soybean forage and hay, respectively. Residue data in soybean forage and hay showed

comparable residues of parent and its metabolite when the fungicide was applied, at the label

. rate, in sprays applied at 20, 2, or I GPA using a ground application device. Samples were

analyzed using an adequate analytical method, and are supported by the available storage stability

data . The number and locations offield trials are in accordance with OPPI S Guideline

860.1500, ChemSAC recommendations, and the conducted field trials reflect the maximum

proposed foliar use pattern. The field trial data for all soybean forage and hay reflecting the

proposed application rate were analyzed and the results support the proposed tolerances for

soybean forage and hay.

The adjuvant data indicate that mostly paraffin and fatty oils were used in the submitted studies

for which adjuvant data are available. The studies which did not list a specific adjuvant had

residue data for pyraclostrobin which were essentially identical to the other studies. ARIA has

determined that there are insignificant differences in the effects, ifnot type, ofthe adjuvants used

in the sprays, between the 2002 and 2008 study; therefore, the no additional field trials are

needed. ARIA recommends for the proposed soybean forage and hay tolerances and the

proposed use of pyraclostrobin.

No soybean seed residue data were collected at the label rate. Data obtained in this study were at

2X the label rate indicated low levels ofpyrac1ostrobin residues (LOQ- 0.08 ppm). No change in

the soybean seed tolerance is required from the proposed use.

The results ofthe submitted field trial data indicate that there is no increase required on soybean

seed. Based on the field trial data and the previou sly submitted soybean processing study,

tolerances for soybean meal and refined oil are not required.

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

EPA National Pesticide Standards Repository.

Page 4 of 27
Pyraclostrobin Swnmary ofAnalytical Chemistry and Residue Data DP#; 37 1252

Regulatory Recommendations and Residue Chemistry Deficiencies

To support the aerial use, BASF has submitted preliminary model generated deposition profile

for aerial application to compare with the ground deposition. However. detai led input and output

data for the model simulations as well as application specifications (i.e. nozzles types, operating

pressure and boom height) for ground equipment were needed to verify the residue bridging data

for aerial application (DP#s 370130, 370133, R. Mille r, F. Khan, 11/1 8/09). The resolution of

these deficiencies were made a condition ofregistration for the low volume application of

pryraclostrobin to com and wheat (DP Barcodes: 368042, 368086, M. Negussie, 1111 0/09). The

resolution of these deficiencies would also affect the recommendations ofthe present petition;

however, new data have been submitted by the petitioner and have been examined by

Environmental Fate and Effects Division (EFED) and found to be adequate (e-mail, B. Anderson,

5/26110).

ARIA recommends for registration for the requested uses of pyraclostrobin on soybeans. There

are no residue chemistry issues that would preclude granting registration for the requested label

change to allow aerial application of pyraclostrobin with spray volume as low as 1 GPA to

soybeans and increases in the followi ng tolerances:

Soybean, forage 11 ppm

Soybean, hay 14 ppm

Since there are no increases in any human food item or increase in pyraclostrobin

application rate. an updated human health risk assessment is not required.

Note to PM: It is recommended that the tolerance expression for 40 CFR §

180.474(a)( I) be changes to: "Tolerances are established for residues of the

fungicide pyradostrobin, including its metabolites and degradates, in or on the

commodities in the table below. Compliance with the tolerance levels specified

below 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-[[[ I-(4-chlorophenyl)-1Hpyrazol-3-yl]oxy]methyl]phenylcarbamate), calculated as the stoichiometric

equivalent ofpyraclostrobin, in or on the commodity."

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 ofthe fungus on the leaf surface. The chemical structure and nomenclature of

pyraclostrobin are presented in Table I. The physicochemical properties ofthe technical grade of

pyraclostrobin are presented in Table 2.

ITABLE I. Test Compound Nomenclature.

Page 5 of2 7
Pyraclostrobin Summary ofAna lytical Chem istry and Residue Data DP#: 371252

TABLE 1. Test Comnound Nome nclature.

Compound

o '"

c,--O-<:1 /Oy"--...OCH, H,C

0

Common name P aclostrobin

Co ~e ri mental name BAS 500 F

IUPAC name methyl N-{2-[ 1-(4-chlorophenyl)-1H-pyrazol-3-yloxymeth yljphenyl}(N-melhoxy)

carbamate

CAS name meth I 2- I- a-chloro hen I -I H- azol-3- I oxvlmeth 'Hnhcnvllmethoxvcarbamate

CAS re ist number 1750 13-18-0

End-use products (EP) Headline® Fungicide, EPA Reg. No. 7969-186; Headline® SC Fungicide, EPA Reg. No.

7969-289

Product Chemist ry data were reviewed by the Registration DIVISIon (DP# 269848 and OP# 274191, 5/3/0 I, 5/ 15/01, and

6n101 , S. Malak).

BASF ' Document Number.

TABLE 2. PtwSicochem ical Pr~erl of Tec hnical Grade Pvractostro bin.

Parameter Value References (MRl m

Meltine point/ranee 63.7_65.2°C 45 1182 13

pH Not aoo licable

Oensi 1.367 a/ern 45118214

Water solubili at 20"C 1.9 ± 0.17 m deionized water. oH 5.8 45 118233

Solvent solubility n-heptane : (0.37 glIOOmL); 2-propanol (3.0 45 118228

glIOOmL); l-octanol (2.42 gi l OOmL); olive oil

(2.80 gl IOOmIL); methanol (10.08 glIOOmL);

>50 gi lOOmL in acetone, ethyl acetate ,

acetonitrile, OCM and toluene.

V, r ressure 2.6 x 10-

10 hPa at 20°C 45 1182 14

Dissociation constant, pK. None (no dissociable moieties}

ctanol:'~ ater partition coefficient, 3.990 mean log P,...; (Po...is 97 72) 45 118215

Lo"(Kow at room temperature

UVIvisible absorption spectrum The structura l identity of BAS 500 F was 1996/10955

confirmed by NMR and MS spectra. UV

molecular extincti on (e [I mor' cm·

I

]): 2.5x 104

at 205 nm; 2.4xI 04 at 275 nm. I

860.1200 Directions for Use

T ABLE 3. Su m mar v of Pro osed/Res is tered Use P a lle rns of reclosrrobln.

Applic. Timing, Formulation Applic . Ma x. Max. PHI Use Directions and Limitations

Type, a nd [EPA Reg. Rate No. Seasonal (days)

Eq uip. N o.) (lb ai/A) App lic. Applic.

p" Rate

Season (Ib avA)

Soybean

Broadcast foliar Headline7 0.10-0.20 2 0.40 21 Min. appLvel. I GPA

spray; Fungi cide

Ground or aerial [7969-186] Resistance management Option B: To

Headline7SC limit the potential for development of

Fung icide resistance, do not make more than two

aeolications of Headline or othe r

Page 6 of 27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 37 1252

TABLE 3. Summarv of Prooosed'Remstered Use Patterns of Pvraclostrobin.

Applic. Timing, Formulation Applic. Max. Max. PHI Use Directions and Limitations

Type, and [EPA Reg. Rate No. Seasonal (days)

Equip. No.] (lb ai/A) App lic. Applic .

pe< Rate

Season I IIb ai/A\

[7969-289J strobilurin fungicide per season.

Applications may begin prior to disease

developmentand continue on a 7- to 14-

day interval.

Conclusion. The submitted use directions are sufficient to allow evaluation of the available

residue data relative to the proposed usc.

860.1300 Nature of the Residue . Plants

HED MARC, DP# 278044, L. Cheng, 10/910I

PP#OF6139, DP# 269668, L. Cheng, 11128/01

The nature ofthe residue in plants is adequat ely understood based on acceptable metabolism

studies conducted on grape, potato, and wheat. The metabolism of pyraclostrobin is similar in

the three crops investigated. Pyraclostrobin and its desmethoxy metabolite (BF 500-3) are the

major residues in crop matrices including livestock feeds; tryptophan was found to be the major

residue in potato tuber and wheat grain when carbon-14 was introduced in the tolyl ring (via the

shikimic acid pathway). The major degradation reactions are the removal ofthe rnethoxy group

from the carbamate nitrogen and breakage of the ether bond .

The HED MARC has determined that for the tolerance and risk assessment, the terminal residues

of concern in plants consist of pyraclostrobin and its metabolite BF 500-3.

860.1300 Nature of the Residue - Livestock

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

PP#OF6139, DP# 269668, L. Cheng, 11128/01

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; pyraclostrobio, 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 .

The HED MARC 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)-lH-pyrazol-3-01(BF 500-5) and 1-(4-chloro-2-hydroxyphenyl)-lH-pyrazol-3-01

Page 7 of 27
Pyrac1ostrobin

(BF 500-8).

Summary ofAnalytical Chemistry and Residue Data DP#: 371252

860.1340 Residue Analytical Methods

PP#OF6139, DP# 269668, L. Cheng, 11/28/0 1

PP#OF6139, DP# 269850, L. Cheng, 11/8/00

Plant Commodities

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

pyraclostrob in and the metabolite SF 500-3 in/on plant commodities: an LCIMSIMS method

(BASF Method D9908) and an HPLCIUV method (Method D9904). The validated method LOQ

for both pyraclostrobin and SF 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 ACSIBEAD for a petition method validation.

Data Collection: Residues of pyraclostrobin and its desmethoxy metabolite SF 500-3 in soybean

RACs were determined using SASF Analytical Method 0 9908 (version II). Briefly, residues

were extracted by shaking with methanol:water:2N HCI (70:25:5; v:v:v); methanol:water (70:30,

v:v) and centrifuged. Residues were then partitioned with cyclohexane and IN HCL saturated

with NaCl, concentrated to dryness, and re-dissolved in buffered methanol :water (80:20, v:v).

The final chromatographic analysis of residues was determined by LCIMSIMS. Total residues of

pyraclostrobin and SF 500-3 are expre ssed as pyraclostrobin equivalents. For each analyte, the

validated method LOQ is 0.02 ppm. There were acceptable concurrent method recovery data .

Livestock Commodities

Enforce ment: Two tolerance enforcement methods were proposed for ruminant commodities:

HPLCIUV method 439/0 and Method 446, consisting ofGCIMS method 446/0 and LCIMSIMS

method 446/1. The HPLCIUV method determines residues of pyraclostrobin per se. Method

446 has a hydrolysis step, and determines residues of pyraclostrobin and its metabolites as SF

500-5 and BF 500-8. The validated method LOQs for BF 500-5 type residues, in parent

equivalents, are 0.01 ppm for milk and 0.05 ppm for tissues, and the validated LOQs for S F 500-

8 type residues, in parent equivalents, are 0.01 ppm for milk, and 0.05 ppm for tissues.

Independent method validation data for the HPLCIUV and LCIMSIMS methods are acceptable.

Radiovalidation data submitted for the GCIM S and LCIMSIMS methods are adequate for liver

and milk, and marginal for muscle. Method 446 has been forwarded to ACSIBEAD for petition

method validation. HED concluded that Method 446 is suitable as an enforcement method. The

petitioner had been requested to modify the proposed enforcement method to include any

modifications made by the EPA laboratory during the Agency laboratory validation should they

be requested. An enforcement method for poultry was reviewed in PP#OF06139. However,

tolerances for poultry egg and tissues have not been established and are not required for the

purpose of these petitions.

Conclusion. There are adequate residue analytical methods for tolerance enforcement and data

collection.

860.1360 Multiresidue Me thods

Page 8 of 27
Pyraclostrobin Summ ary of Analytical Chemistry and Residue Data DP#: 371252

PP#OF6139, DP# 269668, L. Cheng, 11128/01

Pyraclostrobin was successfully evaluated through several ofthe 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 SF 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 ofthe

multiresidue testing for pyrac1ostrobin 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#OF6139, DP# 26966 8, L. Cheng, 11128/01

The storage interval from collection to extraction ranged from 131-197 days (4.3-6.5 months) for

soybean RAC samples in the submitted study. Adequate storage stability data are available

indicating that pyraclostrobin and metabolite BF 500-3 are reasonably stable at 5- 1O°C in

fortified samples of grape juice (juices), sugar beet tops (leafy vegetables), sugar beet roots (root

crop), tomatoes (fruit/fruiting vegetable), wheat grain (non-oily grain), and wheat straw (dry

feed) for up to 25 months, and in fortified samples of peanut nutmeats (oilseed) and peanut oil

for up to 19 months.

The storage intervals and conditions for samples collected from the magnitude ofthe residue and

processing studies discussed in this document are presented below in Table 4.

TABLE 4. Summary of Storage Conditions and Intervals of Samples from C ro p Field Trials.

Matrix MRID Storage Actua l Storage Interval of Demonstrated

Temperature ("'C) Duratio n (Months) Sto rage Stability (months)

Sweet/S our Cherry 47470201 -10 5.7 19-25

Peach 4.9

Plum 3.8

Sorshum Foraae 4747020 3 -5 5.3 19-25

Sorghum Grain 8.2

Sorzhum Sto ver 5.3

Coffee 47470204 5-20 4.1 19-25

Coffee (Green bean,

Cleaned green bean,

Roasted bean s, Dried 47470202

<-5 <1 month 19-25

spent grounds, Liquor

extract, and Instant

coffee).

Conclusion. The storage conditions and durations ofsamples are supported by adequate storage

stability data available indicating that pyraclostrobin and BF 500-3 are stable in frozen

representative plant matrices for the duration ofthe submitted study.

860.1400 Water, Fish, and Irrigated Crops

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

Page 90f27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 371252

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

PP#s 8F7385, 8F7390, and 8E7394, DP# 359 194, M. Negussie, 4/02/09

Livestock dietarYburdens

The potential for transfer ofpyraclostrobin residues of concern to meat, milk, poultry , and eggs

exists because there are several livestock feedstuffs (e.g., soybean forage, seed, and forage) that

are associated with the proposed use in the current petition. The only soybean commodities

which will have higher tolerances than those used in the last estimate of livestock diets are forage

and hay. Since soybean hay and forage are considered feedstuffs only for dairy cattle (Revisions

of Feedstuffs in Table I ofOPPTS Test Guideline 860.1000 and Guidance on Constructing Maximum

Reasonably Balanced Diets (MRBD), 6/30/08), there are no changes in the previous diets for beef

cattle, poultry and swine, and therefore no changes in the associated livestock tolerances for

those commodities are required.

The requested change in tolerance levels for soybean hay and forage only affect the diet for dairy

cattle . The livestock dietary burdens of pyraclostrobin are presented in Table 5, and reflect the

most recent guidance from HED concerning revisions offeedstuff percentages in OPPTS

860.1000 Table I and construction MRBDs. The last MRBD ofpyraclostrobin was calculated

based on the addition ofsorghum grain, sorghum forage, and sorghum stover resulted in a dietary

burden estimated at 9.5 ppm for dairy cattle. Replacing those sorghum items with the similar

soybean commodities, results in an estimated MRBD of 13.7 ppm. The current pyraclostrobin

tolerances for livestock commodities were established based on results from the dairy cattle

feeding study and the Agency's estimated dietary burdens for pyraclostrobin residues, which

were origiually calculated to be 35.4 ppm for dairy cattle (PP#s 8F7385, 8F7390, and 8E7394,

DP# 359194, M. Negussie, 4/02/09).

All data are based on Table 1 Feedstuffs (June 2008). a revision of feedstuffs data found In Table 1(180.1000 OPPTS Test GUide lines). Residue

TABLE 5. Ca lculation of Maxim um Reasonably Balanced Dietary Burdens (MRBDs) of Pyraclostrobin

Resid ues for Livestock. I

Feedstuff Type

% 01)' % Diet Tolerance (ppm) Dietary Contribution

Matter (ppm)

Dairy Catt le R 45%, CC 45%, PC 10%

Legume, hay (cowpea) R 30 5 25 4.16

Barley, grain CC 88 20 0.4 0.091

Cotton, undelinted seed PC 90 10 0.3 0.033

Soybean, forage R 35 20 11 6.29

Soybean, hay R 89 20 14 3.15

Sorghum, grain, grain CC 86 25 0.6 0.15

TOTAL BURDEN -- -- 100 -- 13.7 ,

Page 10 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#; 37 1252

levels for beef and dairy are corrected for moistu re content and are determined by formula : tolerance I %DM x % in diet. R: roughage; CC:

carbohydrate concentrate; PC: protein concentrate.

Typ ical compos itions ofdaily rations for the animals of choice for Tab le I data follow:

High volume milk-producing lactating dairy cows have a daily ration of 45 % R, 404 5 % CC, and 10-15 % Pc.

Livestock feeding studies

MARC, PP#OF6 139, DP# 278044, L. Cheng, 10/9/01

PP#OF6139, DP# 269668 , L. Cheng, 11128/01

The HED MARC discussed the metabolism ofpyraclostrobin in livestock on September 20, 2001

and has concluded that the residues of concern in livestock commodities consist of pyraclostrobin

and its metabolites hydrolyzable to BF 500-5 and BF 500-8 (MARC, PP#OF6139, DP# 278044,

L. Cheng, 10/9/01). The previously submitted dairy cattle feeding data are adequate for the

purpose of establishing tolerances for pyraclostrobin residues. Dairy cows were orally dosed

twice daily for 28 consecutive days with pyrac1ostrobin at dose levels equivalent to 8.8 ppm, 27.2

ppm (mid dose), and 89.6 ppm (high dose). The maximum combined residues of pyraclostrobin

and its metabolites hydrolyzable to BF 500-5 and BF 500-8 were <0.02-<0.0235 ppm (mid dose)

and <0.02-0.175 ppm (high dose) in whole milk, <0.02 ppm (mid dose) and 0.0393-0.102 ppm

(high dose) in skim milk, and <0.02-<0.0561 ppm (mid dose) and 0.131-0.258 ppm (high dose)

in milk fat. These data and the theoretical dietary burden ofpyrac1ostrobin for dairy cattle at 35.4

ppm at that time were used to establish a tolerance of 0.1 ppm in milk (PP#OF6139, DP# 269668,

L. Cheng, 11 /28/01).

Conclusion. The only soybean commodities which will have higher tolerances than those used in

the last estimate oflivestock diets are forage and hay. Since soybean hay and forage are

considered feedstuffs only for dairy cattle, there are no changes in the previous diets for beef

cattle, poultry and swine, and therefore no changes in the associated livestock tolerances are

required .

The current pyraclostrobin tolerances for livestock commodities were established based on

results from the dairy cattle feeding study and the Agency's estimated dietary burdens for

pyraclostrobin residues, which were originally calculated to be 35.4 ppm for dairy cattle. Based

on the updated dairy cattle dietary exposure levels and the residue data from the dairy cattle

feeding study, the existing pyraclostrobin toleranc e for milk at 0.1 ppm is adequate and will not

need to be changed as a result of the proposed uses in this petition.

860.1500 Crop Field Trials

The registrant has submitted data in the form of 3 side-by-side residue field trials on soybean

forage and hay to support reduced spray volumes applications down to I GPA, which will

include aerial applications. The ChemSAC previously reviewed preliminary data from these

studies and indicated that provided there are insignificant differences in the type of adjuvants

used and in the concentrations of these adjuvants in the sprays, between the 2002 and 2008 study,

no additional field trials are needed. The SAC also concluded that new soybean forage and hay

data can be combined with the original data to derive new tolerances for forage and hay, while

included seed data do not support an increase in the soybean seed tolerance (ChemSAC 5/13/09),

Page II of 27
Pyraclostrobin

Soybean Field Trials

Summary of Analytical Chemistry and Residue Data DP#: 371252

MRID 47774701, M. Negussie, 3/16/10

BASF has submitted supplemental field trial data for pyraclostrobin (BAS 500 F) on soybean. A

total of three soybean trials were conducted in EPA Region 5 (IL, 2-trials; lA, I-trial) during the

2008 growing season.

At each test location, an untreated plot (control) and three treatedplots were established. The

treated plots received two foliar broadcast applications of pyraclostrobin (2 lb ai/gal EC

(emulsifiable concentrate); BASF formulation code, BAS 500 OOF) at 0.19-0.21 lb ailA (0.213-

0.235 kg ailha), with a 7-8 day retreatment interval (RTI), totaling a seasonal rate of O.39-0Al lb

ai/A (0.437-0.460 kg ailha). Applications were initiated when the soybeanplants were at the

beginning offlowering (BBCH 60). At one site (R050891), two additional broadcast

applications of pyraclostrobin were made to the treated plots at 0.18-0.21 lb ai/A (0.202-0.235 kg

ailha) with a 7-day RTI, totaling in a seasonal rate ofO.80-0.811b ailA (0.90-0.91 kg ailha). The

third application at this site was made42 days after second application at advanced pod filling

growth stage (BBCH 77) and the fourth application was made at growth stage BBCH 79, 21 days

prior to harvest of mature seed. Each plot was treatedusing water solutions at either 19-21 gallA

(OPA), 2 OPA, and 1 OPA using ground equipment and includes the use of a crop oil

concentrate (COC).

Samples of soybean forage were harvestedat beginning pod development, 12-15 days after the

second application (DASA) and soybean hay samples were harvested 20-21 OASA and allowed

to dry for 5-6 days. Seed samples were harvestedat maturity, 21 days after the last application

(OALA); only for the treatments with four applications.

The residues ofpyraclostrobin and its N-desmethoxy metabolite, 500M07, previously designated

BF 500-3) in/on soybean raw agricultural commodity (RAC) samples (forage, hay, and seed)

were quantitated using a LC/MS/MS method, BASF analytical method number 0 9908 (Version

II). The validated LOQ was 0.02 ppm for each analyte, for a combined LOQ of 0.04 ppm.

Acceptable concurrent method recoverydata for soybean RAC samples were obtained for each

analyte. The method LOD for each analyte in/on soybeanRAe samples was 0.004 ppm.

The results from these analyses indicate that combined residues of pyraclostrobin were 2.6-10.5

ppm (20 OPAl, 1.8-10.1 ppm (2 OPAl, and 1.8-9.8 ppm (l OPAl in/on treated soybean forage

samples, each harvested 12-1 5 DASA. Combined residues ofpyraclostrobin were 5.9-11.4 ppm

(20 OPAl, 3.6- 14.5 ppm (2 OPAl, and 3.9-10.0 ppm (l OPAl in/on soybean hay samples, each

harvested 20-21 DASA. Combined residues of pyraclostrobin were <0.05 and <0.08 ppm (20

OPAl, <0.04 ppm (2 and I OPAl, in/on soybean seed samples, each harvested 21 days after the

fourth application (2X the proposed application rate). The residues of pyraclostrobin between the

various application spray volumes were comparable on all soybean RACs.

TABLE 6. Summary of Residue Data from Crop FieldTrials with Pvractostrobtn.

Commodity Total PHI Analyte Residue Levels

Applic. day, com

Rate GPA n' Min Max HAFT Median M, an Std.

Ib ai/A , Dev.

Page 12 of 27
Pyraclostrobin Summary of Analytical Chemistryand ResidueData DP#: 371252

TABLE 6. Summary of Residue Data from Crop Field Trials with Pvraclostrobm.

Commodity Total PHI Analyte Residue Levels

Applic. days oom

Rate GPA n' Min Mox HAFT Median Mean Std.

Ib ai/A z Dev.

Forage 0.39- 12-15 Pyraclostrobin 20 6 2.26 8.57 8.33 3.01 4.54 2.96

0.4 1 500M07 0.33 2.01 1.98 0.46 0.93 0.81

Total 2.60 10.50 10.30 3.45 5.47 3.76

IPvraclosrrobin

Pyraclostrobin 2 6 1.54 8.22 7.82 2.59 4.00 3.00

500M07 0.2 1 1.89 1.84 0.46 0.84 0.79

Total 1.80 10.10 9.65 3.05 4.85 3.77

IPyrac lostrobin

Pyrac1ostrobin 1 6 1.60 7.95 7.54 2.63 3.95 2.84

500M 07 0.20 1.88 1.76 0.46 0.82 0.74

Total 1.80 9.80 9.30 3.10 4.77 3.58

IPvraclostrobin

Hay 0.39- 20-21 Pyraclostrobin 20 6 4.96 9.52 8.63 7.34 7.03 1.69

0.41 500M07 0.89 1.83 1.73 1.23 1.28 0.38

Total 5.90 11.40 10.40 8.60 8.35 2.06

IPvraclostrobin

Pyraclostrobin 2 6 3.13 11.40 10.56 4.26 6.06 3.56

500M07 0.51 3.06 2.66 0.89 1.36 1.06

Total 3.60 14.50 13.25 5.05 7.42 4.64

IPvrac1ostrobin

Pyrac1ostrobin 1 6 3.37 7.90 7.85 5.26 5.5 1 2.06

500M07 0.55 2.14 1.98 1.16 1.23 0.65

Total 3.90 10.0 9.80 6.40 6.72 2.69

Pvraclostrobin

Seed 0.80- 2 1 Pyraclostrobin 20 2 0.03 0.06 0.05 0.05 0.05 NlA

0.8 1 500M07 <0.02 <0.02 <0.02 <0.02 <0.02 NlA

Total 0.05 0.08 0.07 0.07 0.07 N/A

IPvraclostrobin

Pyraclostrobin 2 2 <0.02 <0.02 <0.02 <0.02 <0.02 NlA

500M07 <0.02 <0.02 <0.02 <0.02 <0.02 N/A

Total <0.04 <0.04 <0.04 <0.04 <0.04 N/A

IPvraclostrobin

Pyraclostrobin 1 2 <0.02 <0.02 <0.02 <0.02 <0.02 N/A

500M07 <0.02 <0.02 <0.02 <0.02 <0.02 NlA

Total <0.04 <0.04 <0.04 <0.04 <0.04 N/A

IPvraclostrobin

n number of individual specimens

2HAFT= Highest Average FieldTrial based oncombinedresidues

'N/A = Not applicable

Field Trial Adjuvants

MRJD47774702

Page 13 of27
Pyraclostrobin Summary ofAnalytical Chemistry and Residue Data DP#: 37 1252

The registrant has submitted a data summary a large part of which was on soybean seeds. The

seed data indicate that whether using the domestically registered products, Headline Fungicide

[7969- 186] or Headline SC Fungicide [7969-289] with an adjuvant added to the tank mix or

foreign products, e.g., BAS 500 OOF, which include several different adjuvants directly in the

formulation, very little pyraclostrobin is found using the label use pattern « LOQ; 0.04).

Summations of the submitted soybean forage and hay adjuvant data is presented in Table 7,

below. The data indicate that mostly paraffin and fatty oils were used in the submitted studies for

which adjuvant data are available. No differences in residue data are apparent between the

studies which did not list a specific adjuvant and those that did residue data for pyraclostrobin

which were essentially identical to the other studies.

TABL.E 7. Summary of Adjuvant Use with Forage and Hay Resi due Data.

Adjuvant Amount Rate App Soybean Soybean

Added Added Vol. Forag e Hay (composition) (% ) (nUA) (GPA' (nn";' Inn';"

2002 Trials

AdSpray 0.5 NR 39 2.78,3.25 0.87, 1.11 (alkylarylpolyalkoxylated

I elvcols and derivatives) 0.5 NR 23 3.81,3.87 2.13,2.15

Penetrator Plus

(non-ionic surfactants in 0.5 NR 30 1.79,1.40 1.0 1,1.04

paraffin oil and buffering

agents)

Agri-Dex

0.5 NR 25 0.84,0.96 1.76,0.05 (non-ionic surfactants in

paraffin oil and buffering 0.5 NR 25 2.71 ,3.37 1.23,1.28 agents)

Activator 90

(alcohol ethoxylates and 0.5 NR 20 1.64,1.54 6.13,5.95

fattv acids)

Preference 0.5 NR 25 1.47,0.74 2.39,2.39 (alkylphenol ethoxylate,

sodium soya fatty acids, 0.5 NR 25 2.2 1,1.59 2.50,2.63

and ldsooroovl alcohol)

Aquagene

(alkylarylpolyoxy-etblyene 0.5 NR 35 1.09,1.08 2.67,2.63 ether, isopropanol, and

fattv acids)

Locally Available 0.5 NR 34 3.06,2.25 1.17,0.91

("not exactly specified?" ) 0.5 NR 30 1.38,1.89 2.10,2.15

0.5 NR 28 0.78,1.02 1.04,0.86

0.5 NR 20 2.55,1.56 2.34,3.7 8

0.5 NR 30 1.74,1.79 2.78,2.36

0.5 NR 30 2.69,3.50 3.47,2.84

0.5 NR 32 1.52, 1.40 2.28 ,2.39

0.5 NR 30 2.22,1.91 2.42 ,2.19

2008 Trials

R-way NR 0.3 20 10.51,10.1 11.35,9.36

(paraffin oil and NR 0.5 2 10.11,9.21 14.46, 11.97

surfactants) NR 0.5 1 9.83,8.77 9.60,10.04

Helena Crop Oil NR 0.5 20 3.35,3.59 8.35,8.78

Page 14 of27
Pyraclostrob in Summary of Ana lytica l Chemistry and Residue Data DP#: 37 1252

TABLE7. Summa of Adjuvant Use with Fo raee and Hav Resid ue Data.

Adjuvant Amoun t Rate App Soybean Soybean

Added Added Vol. Forage Hay (composition) (% ) (ovA) IOPA) (0 0 ';;) (DO';')

(para ffin oil, polyol fatty NR 0.5 2 3.03,3.05 4.32,5.85

acid esters, and

polyethoxylated NR 0.58 I 2.71,3.46 5.50,7.32 deri ati ~)

Prime Oil NR 0.5 20 2.66,2.59 6.18,5. 87

(Paraffin oil and polyol

fatty acid esters, and NR 0.5 2 1.86,1.75 4.31,3.64

polyethoxylated

ivative NR 0.5 1 1.80,2.00 4.05,3.93

Avg 3.03 4.03

Max 10.5 1 14.46

Min 0.74 0.05

StdDev 2.60 3.29

NR- not reported

* Direct quote from MRID 47774702

Conclusion. The petitioner has provided adequate bridging residue data reflecting the maximum

proposed use pattern of pyraclostrobin in/on soybean forage and hay. The combined residues of

pyraclostrobin and its metabolite BF 500-3 did not exceed the proposed tolerance levels of 11.0

ppm and 14.0 in/on soybean forage and hay, respectively, following two applications of the 2.0

Ib/gal EC formulation. The combined residues of pyraclostrobin were 1.8-10.5 ppm using 1-20

OPA application volume in/on treated soybean forage samples, harvested at 12-15 PHI.

Combined residues of pyraclostrobin were 3.6-14.5 ppm using 1-20 GPA application volume

in/on soybean hay samples, harvested at 20-21 PHI. Residue data in soybean forage and hay

showed comparable residues of parent and its metabolite when the fungicide (BAS 500 00 F

Fungicide) was applied, at the label rate, in sprays applied at 20, 2, or 1 GPA using a ground

application device. Samples were analyzed using an adequate analytical method, and are

supported by the available storage stability data. The number and locations offield trials are in

accordance with OPPTS Guideline 860.1500, ChemSAC recommendations, and the conducted

field trials reflect the maximum proposed foliar use pattern.

The field trial data for all soybean forage and hay reflecting the proposed application rate

(submitted here and previously submitted in MRID 45903602) were entered into the Agency's

tolerance spreadsheet as specified by the Guidance f or Setting Pesticide Tolerances Based on

Field Trial Data SOP to determine an appropriate tolerance level; see Appendix II. The

tolerance spreadsheet recommends for the proposed tolerances of 11.0 ppm and 14.0 ppm for

soybean forage and hay, respectively. No soybean seed residue data were collected at the label

rate. Data obtained in this study were at 2X the label rate indicated low levels of pyraclostrobin

residues (LOQ- 0.08 ppm). No change in the soybean seed tolerance is required from the

proposed use.

The adjuvant data indicate that mostly paraffin and fatty oils were used in the submitted studies

for which adjuvant data are available. The studies which did not list a specific adjuvant had

residue data for pyraclostrobin which were essentially identical to the other studies. ARIA

concludes that there are insignificant differences in the effects, if not type, ofthe adjuvants used

Page 15 of 27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 37 1252

in the sprays, between the 2002 and 2008 studies; therefore , the no additional field trials are

needed. ARIA recommends for the proposed soybean forage and hay tolerances and the

proposed use of pyraclostrobin.

860.1520 Processed Food and Feed

PP#s 3F658 1, 2F6431 , 2E647 3, 3E6548, 3E6553, 3E6774, and 2F6139 ; DP#s: 28 1042, 286732,

287729, 288459,290342,290343,290369.292440,293088,293684, 295893,29817 8; L. Cheng,

7/26/04

The previously submitted soybean proc essing study indicates that the combined residues of

pyraclostrobin and its metabolite BF 500-3 may concentrate slightly in soybean hulls (1.3x

average processing factor) but do not appear to concentrate in soybean meal and refined oil.

Conclusion. The results ofthe submitted field trial data indicate that there is no increase required

on soybean seed. Based on the field trial data and the previously submitted soybean processing

study, tolerances for soybean meal and refined oil are not required.

860.1650 Submittal of Analytical Reference Sta ndards

Analytical standards for pyraclostrobin and its regulated metabolite s (BF 500-3) are currently

available in the EPA National Pesticide Standards Repository (e-mail corre spondence with T.

Cole. 2/17/09).

860.1850 Confined Accumulation in Rota tional Crops

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

PP#OF6139, DP# 269668, L. Cheng, 11/28/0 1

An adequate confined rotati onal crop study was reviewed in PP#OF61 39. 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 SF 500-3.

860.1900 Field Accumulation in Rota tional Cro ps

PP#OF6139, DP# 26966 8, L. Cheng, 11128/01

A limited field rotational crop study was reviewed in PP#OF6139. The results indicate that

residues ofpyraclostrobin 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

vvrapper 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 2lb/gal EC formulation at

0.19 - 0.20 lb ai/A1application. Residues ofpyraclostrobin in/on one sample of wheat straw from

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

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

ppm. Residue s of metabolite BF 500-3 were nondetectable «0.02 ppm) in/on all samples of

wheat straw.

Page 16 of 27
Pyrac1ostrobin Summary ofAnalytical Chemistry and Residue Data DP#: 371252

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

The HED MARC (DP# 278044, L. Cheng, 10/9/01) has determined that for purposes oftolerance

and dietary risk assessments, the residue s of concern in plant and rotational crop commodities

include pyraclostrobin and its desmethoxy metabolite, BF 500 The residues of concern in

livestock commodities include pyraclostrobin and its metabolites convertible to 1~(4

chlorophenylj-Ijf-pyrazol-S-ol (BF 500-5) and 1-(4-chloro-2-hydroxyphenyl)-IH-pyrazol-3-ol

(BF 500-8).

Pyraclostrobin tolerances for plant commodities are listed in 40 CFR §180.582 (a)(I) and are

expressed in terms ofthe combined residues ofthe fungicide pyraclostrobin (carbamic acid, [2-

[[[1-(4-chlorophenyl)-I H- pyrazol-3-yl]oxy]methyl]phenyl]methoxy-, methyl ester) and its

desmethoxy metabo lite (methyl N-[[[ 1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyIJphenyl

carbamate), expressed as parent compound.

Pyraclostrobin tolerances for livestock commodi ties are listed in 40 CFR §180.582 (a)(2) and are

expressed in terms ofthe combined residues ofthe fungicide pyraclostrobin and its metabolites

convertible to 1-(4-chlorophenyl)-1H-pyrazol-3-01and 1-(4-chloro-2-hydroxyphenyl)-IHpyrazol-Scol, expressed as parent compo und.

The field trial data for all soybean forage and hay reflecting the proposed application rate were

entered into the Agency 's tolerance spreadsheet as specified by the Guidance for Setting

Pesticide Tolerances Based on Field Trial Data SOP to determine an appropriate tolerance level.

The tolerance spreadsheet recommends for the proposed tolerances of 11.0 ppm and 14.0 ppm

for soybean forage and hay, respectively.

There are no Codex MRLs for pyraclostrobin for the crop commodities discussed in this

docwnent.

A summary ofthe recommended tolerances for the crop commodities discussed in this document

is presented in Table 6.

TABLE 6. Tolerance Summary for Pvraclostrobin.

Commodity Proposed Recommended Comments;Correct Commodity Definition

Tolerance (oom) Tolerance (ppm)

Soybean, foraae 11.0 I I

Soybean. hay 14.0 14

References

DP#s:

Subject:

281042 ,286732,287729,288459,290342,290343,290369,292440,293088,

293684,295893,298178

Pyraclostrobin. PP#3F0658 1, 2F06431, 2E6473, 3E6548, 3E6553, 3E6774, and

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

Page 17 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 371252

From:

To:

Dated:

MRIDs:

DP#s:

Subject:

From:

To:

Dated:

MRIDs:

DP#:

Subject:

From:

To:

Dated:

MRIDs:

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#OF06139 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.

L. Cheng

C. Giles-Parker/J. Bazuin

7/26/04

45596211 ,45623406,45623407, 45623408,4562341 0,45645801 ,45645802,

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

45903601 ,45903602,46033901-04,46084401-04,461 091 01 ,461 091 02

269668,272771,272789,274095,274192,274471 ,274957,275843, and278429

PP#OF06139. Pyraclostrobin on Various Crops: Bananas (import), Barley,

Berries, Bulb Vegetab les, Citrus Fruits, Cucurbit Vegetab les, 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 Conn Vegetables, and Wheat. Review of

Analytical Methods and Residue Data.

L. Cheng

C. Giles-Parker!J. Bazuin

11128/01

45118428-4511 84-37, 45118501-451 18512, 4511 8514-451 18537, 4511 8601-

4511 8625, 451 60501, 45272801,45274901 ,45321 101,45367501 ,45399401, and

45429901

278044

PP# OF06139. PC Code 099100. Pyrac1ostrobin. Outcome of theHED

Metabolism Assessment Review Committee (MARC) Meeting Held on

September 20, 2001.

L. Cheng

Y. Donovan

10/09/01

None

Page 18 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 371252

DP#:

Subject:

From:

To:

Dated:

MRlDs:

DP#:

Subject:

From:

To:

Dated:

MRlDs:

269850

PP# OF06139. Pyraclostrobin (BAS 500F) in or on Various Crops. Request for

Tolerance Method Validation (TMV) Trial.

L. Cheng

F. D. Griffith, Jr.

11/8/00

45118505,45118504,45118509,45118510,45118501,4511 8503,45118507,

45118514

281042,286732,287729,288459, 290342,290343,290369,292440,293088,

293684,295893,298178

Pyraclostrobin. PP#3F0658 1, 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#OF06139 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.

L. Cheng

Cynthia Giles-Parker

7/26/04

455962 11,45623406,45623407, 45623408, 45623410,4564580 1,45645802,45645803,

45645804,45 702901, 45765401, 45832001 ,45 858801,45858802,45903601 ,45903602,

46033901-04,4608440 1-04,46 109101,46109 102

Attachments:

Appendix I- International Residue Limit Status sheet

Appendix II. Tolerance Assessment Calculations

Page 19 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 37 1252

Appendix I - International Residue Limits

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: (carbam ic Common Name: [EJ Propo sed tolerances Date: 5/10/10

acid, [2-[[[1-(4- Pyrac1ostrobi n 0 Reeva luated tolerance

chloroph enyl)-l H-pyrazol-3- o Other

y1]oxy]methy1]phenyI]methox

y-, methyl ester) and its

desmethoxy metabolite

(methyl-N-[[[1-(4-

chloropheny1)-l H-pyrazol-3-

yI]oxy]methyl]ph enylcarbam

ate), expressed as parent

compound

Codex Stat us (Maximum Residue Lim itsl U. S. To lerances

UNo Codex proposal step 6 or above Petition Numbers: PP#9F7569

No Codex proposal step 6 or above for the crops Other Identifier:

reauested

Residue definition (step 8/CXL): pyrac1ostrobin ReviewerslBranch: W. Cutchin

Residue definition in PP#8F7385. PP#8F7390, and

PP#8E7394: Combined residues ofpyrac1ostrobin

and BF 500-3, exnre ssed as nvrac1ostrobin.

Crop (s) MRL (mglkg) Crop (s) Recommended

Tolerance (ppm)

Soybean, forage 11.0

SoYbean, hay 14.0

Page 20 of27
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 37 1252

Limits for Canada Limits for Mexico

DNo Limits DNo Limits

...j No Limits for the crops requested D No Limits for the crops requested

Residue definition: Residue defmition : Mexico adopts Codex and/or

fant: methyl [2-[[[1-(4-chlorophenyl)- IH-pyrazol-3- US MRLs/to lerances for its export purposes.

l]oxy]methyl]pheny1]methoxycarbam ate, including the

metabolite [2-[[[ I(4-chlorophenyl)-I H-pyrazol -3-

I]oxy]methyl]phenyl]carbam ate

ivestock: methyl [2-[[[ 1-(4-chlorophenyl)-IH-pyrazol-3-

I]oxy]methyl]phenyl]methoxycarbamate, including the

metabolites convertible to 1-(4-chlorophe nyl)-1H-pyrazol-

-01and 1-(4-chloro-2-hydroxypheny1)-I H-pyrazol-3-ol

Croo (s) MRL (mVklll Croo ts MRL (mVk l!: l

S,FunkIM,Ne ussie, 05/1212010.

Page 21 of27
Pyraclostrob in Summary ofAnalytical Chemistry and Residue Data DP#: 37 1252

Appendix II. Tolerance Assessment Calculations

The field trial data for all soybean forage and hay reflecting the proposed application rate

(submitted here and previously submitted in MRID 45903602) were entered into the Agency's

tolerance spreadsheet as specified by the Guidance f or Setting Pesticide Tolerances Based on

Field Trial Data SOP to determine an appropriate tolerance level; see Appendix II. The

tolerance spreadsheet reconunends for the propo sed tolerances of 11 .0 ppm and 14.0 ppm for

soybean forage and hay, respectively.

Reaulator: EPA

Chemical: pyraclo

Cron: SOY foraee

PHI: 12-15 day

App. Rate :

Submitter:

Residues

2.78

3.25

0.87

1.1 1

3.81

3.87

1.39

1.79

0.84

0.96

2.71

3.37

1.38

1.89

0.78

1.02

1.54

1.64

1.56

2.55

1.74

1.79

2.69

3.5

0.74

1.47

1.59

2.21

Page 22 of27
Pyraclostrobln Summary of Analytical Chemistry and Residue Data

1.4

1.57

1.08

1.09

1.91

2.22

10.5

10.1

10.1

9.2

9.8

8.8

3.3

3.6

3

3.1

2.7

3.5

2.7

2.6

1.9

1.8

1.8

2

Page 23 of27

DP#: 371252
Pyraclostrobin Summary of Analytical Chemistry and Residue Data DP#: 371252

Lognormal Probabilit y Plot

• EPA p y r a c l o soy forage 12 - 15 d.ay

y • 67~ 7 • .8 ~n

R' • l5

11 .00 00 .' . • •

5 .50 00

2 . 7 5 0 0

., .. ..' , .'

LJ75 0

•

-' •

, 2 0 ) 0 7 0 8 0 ~O 95 98 .9

•

, 0 . 60 7S L --:'.L=- _ c ,

Regulator: EPA

Chemi cal: pyr a c l o

Crop : soy forage

PHI : 1 2 -15 day

App . Rate:

Submi t ter:

n , 52

mi n: 0.74

max : 10 .50

median: 1. 9 6

ave r a ge: 2 .9 7

95t h Perc entile 99t h P erce ntile 99 .9 t h Percen tile

EO Me thod I 8.0 10 12

Normal (9 .0 ) (11 ) (-- )

9 5 /99 Ru le 8 . 0 12 19

( 10) (17 ) ( - - )

EO Meth od II 7 .0

Di s t r ibu t i on - Fre e

Mean+ 3SD 11

UCLMedian9 5t h 10

Approximate 0.9358

Sh a p iro-Francia 0.05 > = p-value > 0.0 1 , Re j e c t lognormality assumption

No rmalitv Test

Would you like the above values rounded? (Y or N) == > y

Page 24 of 27
Pyraclostrobin Summary of Analytical Chemistry andResidueData

Reeulator: EPA

Chemical: I ovraclo

Croo: SOY hay

PHI: 2 1 dav

Ann. Rate:

Submitter:

Residues

0.87

1.11

0.91

1.17

2.13

2.15

1.0 1

1.04

0.05

1.76

1.23

1.28

2.1

2.15

0.86

1.04

5.95

6.13

2.34

3.78

2.36

2.78

2.84

3.47

2.39

2.39

2.5

2.63

2.2 8

2.39

2.63

2.67

2.19

2.42

11.4

Page 25 of27

DP#: 37 1252
Pyraclostrobin Summaryof AnalyticalChemistry and Residue Data DP#: 371252

9.4

14.5

12

9.6

10

8.4

8.8

4.3

5.8

5.5

7.3

6.2

5.9

4.3

3.6

4

3.9

Logno rma l Probability Pl o t

• EPA pyraclo soy hay 2 1 d.ay y . o . 90 91 x • 1. 0s

,, ' _ 0.nS5

15 .00 0 0

? ,S OOo

) , 1 500

1 . 8 ? SO

0 .n1 5

O , U U

• •

0 ,n ..

O . U12

0 ,0 586

•

" s . 0 3 0 eo 10 80 so

0.OH3 L _

'-'

Puentl l ..

Page 26 of27
Pyraclostrobin Summary of Analyt ical Chemistry and Residue Data DP#: 371252

Regulator : EPA

Chemical : pyracl o

Crop: soy hay

PHI : 21 day

App . Rate:

Submitter:

n , 52

min : 0 .05

max : 14. 50

median : 2. 6 3

average : 4. 04

95th Percentile 9 9th Pe r c e nt i l e 99 .9th Pe r c en t i l e

EU Method. I 10 12 15

Normal ( 11) (14 ) ( - - )

95 /99 Rule 14 30 55

( 25) (4 5 ) (- - )

EU Method I I 12

Distribution-Free

Mean+3SD I'

UCLMedian95th 13

Approxima te 0 .8855

Shapiro-Francia p -va lue < = 0 .01 : Re ject l o gn or ma lit y ass umpt i on

Normality Test

Wou l d you like the above values rounded? (Y or N) == >

Page 27 of27

y