Boscalid Summary of Analytical Chemistry and Residue Data Barcode D421150



### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D

. C. 20460

O FFI CE OF CHEMICA L SA FE TY AND

POLLUTION P R E V ENTI ON



### MEMORANDUM



### Date:

S ubj ect:

From:

Through:

To: 06/30/2014

Boscalid. 

### Petition for the E stablishment of Permanent Tolerances and Registration for Use on Herb Subgroup 19A and Dill Seed. Request for Crop Group Expansions/ Revisi ons for Stone Fruit Group 12-12 a nd Tree Nu t Gro u p 14-12. Summary of Analytical Chemistry and Residue Data.

PC Code: 128008 DP Barcode: D421 150

Decision No.:484932 Reg i stration Nos.: 7969-198, 7969-199

Petition No.: 3E8215 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case No .: N / A

TXR No.: NA CAS No.: 188425-85-6

MRID Nos.: 4701480 1 -47014803 40 CFR: 180.589



### Stephen Funk

, Senior Chemist 

# {1.' / 1/1!

# ~ 

# Y

Risk Assessment Branch III (RAB III ) 

# J 

# F**~I** ()

Health Effects Division (HED; 7509P

Risk Assessmen t Branch 

### III (RABIII)/J / 

# j Christine Olinger, Branch C hief**~**



### Hea l th Effects Division (HED; 7509'(Y**~**



### Barbara Madden, RM05

Andrew Ertman Registration Division (RD; 7505P)

And

Barry O'Keefe, Senior Biologist

Ri sk Assessment Bran ch III (RAB B I)

Health Effects Di visio n (HED; 7509P)

Page 1 of29Boscal id Summary of Ana l yt ic al Chemistry and Residue Data Barcode 0421150

OCSPP860 MRID Nu mber Ti tle

Se r ies

G uideline

860. 1 500 4701480 1 D. Carpen ter

, 2006

, BAS 5 I 6 : Magnitude of the Residue in Dill. Crop Field U npublished Study Prepared by BASF Agro Research, University of

Trials Florida and Articho ke Research Assn.

, Project No

. 08691 / 03 / BAR03.

08691

, 2000 / 50010 1 9.214p.

860. 1 500 470 1 4802 D

. Ca rpenter

, 2006

, BAS 5 1 6: Magnitude of the Residue on Chives. Crop Field Unpublished Study Prepared by BASF Agro R esea rch

, University of

Trials Maryland and U. S. Dept of Agriculture Agr. R es

. Service

, Proj ect Number

08793

, 08793 / 03 / BAR05

. I 73 p.
860.1500 470 1 4 803 D

. Carpenter

, 2006. BAS 5a6 : Magnitude of the Residu e on Basil. Crop Field Unpubli shed Study Prepared by BASF Agro Re search, Cornell Universi ty
Trials and Artichoke Research Assn

, Project Number 08792

, 08792 / 03 / BAR04

. 203 p,



### Page 2 of29Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 3 of 29 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............ 5

2.0 Regulatory Recommendations

................................ ................................ ............................ 6

2.1 Data Deficiencies/Data Needs

................................ ................................ .......................... 6

2.2 Tolerance Considerations

................................ ................................ ................................ . 6

2.2.1 Enforcement Analytical Method

................................ ................................ ............... 6

2.2.2 Recommended Tolerances

................................ ................................ ........................ 7

2.2.3 Revisions to Petitioned

- For Tolerances

................................ ................................ .... 7

2.2.4 International Harmonization

................................ ................................ ..................... 8

2.3 Label Recommendations

................................ ................................ ................................ .. 8

3.0 Introduction

................................ ................................ ................................ ......................... 8

3.1 Chemical Identity

................................ ................................ ................................ ............. 8

3.2 Physical/Chemical Characteristics

................................ ................................ ................... 9

3.3 Pesticide Use Pattern/Directions for Use (860.1200)

................................ ....................... 9

4.0 Metabolite/Degradate Residue Profile

................................ ................................ .............. 10

4.1 Nature of the Residue

................................ ................................ ................................ ..... 10

4.1.1 Summary of Plant Metabolism (860.1300)

................................ ............................. 10

4.1.2 Summary of Livestock Metabolism (860.1300)

................................ ..................... 10

4.1.3 Summary of Confined Rotational Crops (860.l850)

................................ ............... 11

4.1.4 Summary of Metabolites and Degradates

................................ ............................... 11

4.2 Comparison of Metabolic Pathways

................................ ................................ .............. 12

4.3 Residues of Concern Summary and Rationale

................................ ............................... 12

5.0 Residue Profile

................................ ................................ ................................ .................. 13

5.1 Residue Analytical Methods (860.1340)

................................ ................................ ........ 13

5.1.1 Data Collection Methods

................................ ................................ ........................ 13

5.1.2 Multi

- Residue Methods (860.1360)

................................ ................................ ........ 14

5.1.3 Tolerance Enforcement Methods

................................ ................................ ............ 14

5.1.4 Submittal of Analytical Reference Standards (860.1650)

................................ ...... 14

5.2 Storage Stability (860.1380)

................................ ................................ .......................... 14

5.3 Residue Data

................................ ................................ ................................ .................. 15

5.3.1 Crop Field Trials (860.1500)

................................ ................................ .................. 15

5.3.2 Field Rotational Crops (860.1900)

................................ ................................ ......... 16

5.3.3 Processed Food and Feed (860.1520)

................................ ................................ ..... 17Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 4 of 29 5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

................................ .............................. 17

5.3.5. Food Handling (860.1460)

................................ ................................ ...................... 18

5.3.6 Water, Fish, and Irrigated Crops (860.1400)

................................ .......................... 18

6.0 Tolerance Derivation

................................ ................................ ................................ ........ 18

Appendix A. Tabular Summary of Metabolites

................................ ................................ ........... 19

Appendix B. Metabolic Pathways

................................ ................................ ................................ 23

Appendix C. International Residue Limits Table

................................ ................................ ........ 26

Appendix D. OECD MRL Calculation Procedure Inputs/Outputs

................................ .............. 27Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 5 of 29 1.0 Executive Summary

Boscalid, 2

- chloro

- N

- (4  ́

- chloro[1,1  ́

- biphenyl]

- 2

- yl)

- 3

- pyridinecarboxamide, is a carboxamide (anilide) class fungicide that inhibits mit ochondrial respiration, thereby inhibiting spore germination, germ tube elongation, mycelial growth, and sporulation in all major stages of fungal development and reproduction necessary for disease development in a variety of vegetable, fruit and row crops

. There are currently two water

- dispersible granular (WDG) boscalid end

- use products (EPs) registered to BASF in the US for use on food/feed crops, one containing only boscalid and one which is a mixture of two active ingredients. The single active ingre dient formulation is a 70% WDG (Endura ® 

### Fungicide; EPA Reg. No. 7969

- 197) and the mixture formulation is a WDG containing 25.2% boscalid and 12.8% pyraclostrobin (Pristine ®


### Fungicide; EPA Reg. No. 7969

- 199). The latter is the subject of the current regist ration action.

Only boscalid is addressed in this document; pyraclostrobin is being evaluated separately.

The Interregional Research Project Number 4 ( IR

- 4) is proposing new uses for boscalid (Pristine ® 

### Fungicide) on the herb subgroup 19A and dill. The relevant field trial data were reviewed previously, and that review is incorporated by reference: D3 73144

, C. Olinger,

11 / 27 /20 11

. The proposed use for the herb subgroup 19A and for dill is up to two applications of

a WG formulation with a seasonal maxi mum rate of 0. 58 lb ai/acre and a 0 day pre

- harvest interval ( PHI )

.

IR4 is also requesting crop group conversions for stone fruit 12

- 12 and nut tree group 14

- 12.

The nature of boscalid residues in primary crops and livestock is adequately understood, based on the acceptable metabolism studies on lettuce, grapes, beans, goats

, and hens. For purposes of tolerances and dietary risk assessment, the HED has concluded that the residue of concern in plant commodities is boscalid, an d the residue of concern in livestock commodities include boscalid, its 5

- hydroxy metabolite ( M510F01 )

, and the glucuronic acid conjugate of the 5

- hydroxy metabolite (M510F02)

.

An adequate gas chromatograph y/ mass spectrometric detection (GC/MS) method (Method D0008) is available for enforcing boscalid tolerances in plant commodities, and an adequate GC/electron capture detection method (Method DFG S19) is available for enforcing the

tolerances in livestock commodities. Thes e methods have been found adequate by the Analytical Chemistry Branch (ACB) of the Biological and Economic Analysis Division ( BEAD )

.

An adequate data collection method is available for plant commodities

. Boscalid residues in plant commodities were determ ined using liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) method (BASF Method D9908). This method was adequately validated in conjunction with the analysis of field trial study samples , and the validated limit of quantitation (L OQ) is 0.05 ppm for boscalid in all plant commodities tested.

Residues of boscalid and its metabolite M510F01 were not adequately recovered using the

multiresidue methods.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 6 of 29 Adequate storage stability studies are available indicating that boscalid is r elatively stable at

≤

- 20oC in various plant commodities for up to 24 months. The available storage stability data are adequate and support the storage conditions and durations for chives, dill, and basil samples

from the current field trials.

There are n o feed commodities associated with chives, dill, and basil. Therefore, the livestock diets are not impacted, and the existing livestock commodity tolerances remain adequate.

The data generated from chives, dill, and basil field trials are adequate and su pport the proposed uses of the 25% WDG formulation of boscalid on these crops. An adequate number of tests were conducted on the crops in the appropriate geographic regions, and the tests were conducted at ~1x the proposed use rate. Samples were collected around the proposed preharvest interval (PHI) and analyzed for residues of boscalid . Samples of basil from each trial were d ried and analyzed to provide data for dried herbs.

Adequate confined, limited and extensive field rotational crop studies are available supporting the existing tolerances for indirect residues of boscalid in rotational crops. These data support

the 14

- day plant

- back interval currently specified for crops without boscalid uses. No additional rotational crop data are required for purposes of this petition.

2.0 R egulatory R ecommendations

HED has examined the residue chemi stry database for boscalid. There are no residue chemistry considerations that would preclude granting the requested registration and establishing the

recomm ended tolerances for boscalid on the herb subgroup 19A (fresh and dried) and on dill

seed . The specific tolerance recommendations are discussed in 2.2, and label modifications are

discussed in section 2.3

.

The requested crop group conversions are acceptable.

2.1 Data Deficiencies/Data Needs

There are no deficiencies or data needs related to the requested new registrations, new tolerances, and crop group conversions.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

PP#1F6313; DP# 278385, M. Nelson, 8/15/2003 DP# 284510; D. Swineford and E. Kolbe; 8/12/2003 (PMV memo )



### An adequate gas chromatograp h y/mass spectrometry ( GC/MS ) method (Method D0008) is available for enforcing boscalid tolerances in plant commodities. Residues are extracted using an aqueous organic solvent mixture followed by liquid/liquid partitioning and column clean

- up.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 7 of 29 Quantitation is by GC/MS , using selected ion monitoring (SIM) of major ions. The method lists monitoring ions of m/z 342, 142, or 140, and notes that any ion can be used for quantitation based on the cleanness of the chromatograms. Quantitation is performed using an external

calibration curve of boscalid standards. Adequate validation data were submitted, including independent labo ratory validation (ILV) data (MRID 45405101). The validated LOQ is reported to be 0.05 ppm for residues of boscalid in plant matrices. The ACB/ BEAD concluded that the method is acceptable for enforcement purposes in plants

.

2.2.2 Recommended Tolerances

It is recommended that tolera n ces be established for residues of the fungicide boscalid , including its metabolites and degradates, in or on dill seed and the herb subgroup 19A. Compliance with the tolerance levels is to be determined by measuring only boscalid

, 

### 3

- pyridinecarboxamide, 2

- chloro

- N

- (4′

- chloro[1,1'

- biphenyl]

- 2

- yl) . The tolerance expression is aligned with the requirements of the S. Knizner memo dated 05/27/2009.

Table 2.2.2 . Tolerance Summary for Boscalid Commodity Proposed

Tolerance (ppm) Existing

Tolerance HED

- Recommended

Tolerance (ppm) Comments ( correct commodity definition ) Herb subgroup

19A 190

- 150

Dill, seed 300

- 100
Fruit, stone, group 12 - 3.5 Revoke Crop group conversion

Fruit, stone, group 12

- 12 3.5

- 3.5 Crop group conversion

Nut, tree, group

14 - 0.70 Revoke Crop group conversion

Nut, tree, group

14

- 12 0.70

- 0.70 Crop group conversion

Pistachio

- 0.70 Revoke Crop group conversion. Member of group 14

- 12.



### 2.2.3 Revisions to Petitioned

- For Tolerances

The stone fruit and tree nut group conversions occur without modification of the existing

tolerances.

The recommended tolerance for the herb subgroup 19A is 150 ppm, based on the HAFT for basil and the processing factor for drying. Dried basil had residues in excess of those found on dillweed, fresh basil, and chives. The petitioned for tolerance of 190 ppm is not supported by the

field trial data and the Organization for Economic Cooperation and Development ( OECD ) tolerance calculation procedure.

The recommended tolerance for dill seed is 100 ppm, based on evaluation of the 0 day PHI data

with the OEC D calculation procedure. It appears that proposed 300 ppm tolerance included data from an exaggerated application rate.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 8 of 29 A revised Section F is needed for the herb subgroup 19A and for dill seed.

2.2.4 International Harmonization

Canada and Codex have not established maximum residue limits ( MRLs )/toler ances for herbs or dill seed, and therefore there is no harmonization issue.

For stone fruit, Canada has an MRL of 1.7 ppm and Codex has and MRL of 3 ppm. The US tolerance is 3.5 ppm, based on the evaluation of peach, plum, and cherry data (D364447, A. Acierto, 10/16/09). The individual commodity tolerance estimates were 1.6 ppm for plum, 3.0 ppm for peach, and 3.5 ppm for cherry. The Canada MRL of 1.7 ppm was the former US tolerance prior to the la t est data review. The tolerance cannot be lowered to 3 ppm to harmonize with Codex, as the cherry data necessitate a higher value. The tree nut tolerance (0.7 ppm) is harmonized with Canada. The Codex tree nut MRL (0.05 ppm) is lower than the US toler ance, and harmonization is not possible.

2.3 Label Recommendations

No changes to the Pristine label are necessary.

3.0 Introduction

Boscalid is a carboxamide (anilide) class fungicide that inhibits mitochondrial respiration, thereby inhibiting spore ge rmination, germ tube elongation, mycelial growth, and sporulation in all major stages of fungal development and reproduction necessary for disease development in a variety of vegetable, fruit and row crops. It is formulated with pyraclostrobin.

3.1 Chemi cal Identity

Table 3.1. Nomenclat ure of Boscalid and its Hydroxy Metabolite.
Compound

Common name Boscalid; Nicobifen Company experimental name BAS 510 F

IUPAC name 2

- chloro

- N

- (4 

### ׳

- chlorobiphenyl

- 2

- yl)nicotinamide

CAS name 2

- chloro

- N

- (4'

- chloro[1,1'

- biphenyl]

- 2

- yl)

- 3

- pyridinecarboxamide Molecular weight 343.2 CAS registry number 188425

- 85

- 6

End

- use product (EPs) 25.2% WDG (Pristine ® Fungicide; EPA Reg. No. 7969

- 199, also contains 12.8% pyraclostrobin)Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 9 of 29 Table 3.1. Nomenclat ure of Boscalid and its Hydroxy Metabolite.
Hydroxy

- metabolite

Common name Boscalid hydroxy metabolite Company experimental name M510F01 (glucuronide conjugate

– M510F02)

CAS name 2

- chloro

- N

- (4'

- chloro

- 5

- hydroxy

- biphenyl

- 2

- yl)nicotinamide Molecular weight 359.2



### 3.2 Physical/Chemical Characteristics

Table 3.2. Physicochemical Properties of Boscalid.

Parameter Value References
Melting point/range 142.8

- 143.8  C MRIDs 45404802 and

45404804

- 45404809 pH NA (does not dissociate in water) Relative Density (20oC) 1.381g/cm 3
Water solubility (20oC) 4.64 mg/L at pH 6 Solvent solubility (g/100 mL at 20oC) acetone 16

- 20 ethyl acetate 6.7

- 8.0

methanol 4

- 5 2

- propanol <0.01

acetonitrile 4

- 5 dichloromethane 20

- 25

toluene 2

- 5 n

- heptane <0.01

1

- octanol <0.01 olive oil 2.9
N,N

- DMF >25
Vapor pressure 7 x 10

- 9 hPa Dissociation constant, pK a None (does not dissociate in water) Octanol/water partition coefficient, Log(K OW ) 2.96

UV/visible absorption spectrum UV molecular extinction (e[lmol

- 1 cm - 1 ]): 3.15

x10 4 at 228 nm; 1.53 x10 3 at 290 nm



### 3.3 Pesticide Use Pattern/ Directions for Use (860.1200)

Table 3.3 Summary of Proposed Directions for New Use of Boscalid 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

Herb Subgroup 12A and Dill

Foliar, ground or

aerial 25.2%

Pristine® WG

7969

- 199 0.29 2 0.58 0 For aerial application, use no less than 5 gallons of spray solution per acre. Repeat applications at a minimum of 7 days. To limit development of resistance, do not make more than 2Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 10 of 29 Table 3.3 Summary of Proposed Directions for New Use of Boscalid 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

applications per season. The restricted entry interval ( REI ) is 12 hou rs.



### The proposed label for end use product 7969

- 199 (Pristine® fungicide) includes changes for crop group/subgroup conversions. The stone fruit group was expanded from the commodities of group 12 to the commodities of group 12

- 12. The tree nut group was expanded from the commodities of group 14 to the commodities of group 14

- 12. No changes were made in the good agricultural practices (GAPs) for stone fruits and tree nuts from the previous label of

06/04/2012.

Conclusions: The submitted use directions are sufficient to allow for evaluation of the submitted residue data relative to the proposed use pattern for herb subgroup 19A and dill. The proposed label changes related to crop group/subgroup conversions are acceptable. There are no label

deficiencies.

4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue

4.1.1 Summary of Plant Metabolism (860.1300)

PP#1F6313 ; DP# 278385; M. Nelson; 8/15/2003 HED MARC Decision Memo; DP# 286786; M. Nelson; 1/09/2003



### The nature of boscalid residues in primary crops is adequately understood, based upon acceptable grape, lettuce and bean metabolism studies; these studies were reviewed in the initial boscalid petition, PP#1F6313. No significant metabolism of boscalid occurr ed in grapes or lettuce; unchanged parent was the only component identified, accounting for 92

- 98% and 99% total radioactive residues (TRR), respectively. In bean plants, boscalid metabolized slowly; unchanged parent was the major component identified, ac counting for up to 72% TRR in dry bean seeds, and 99% TRR in bean plants. Cleavage products, 1

- (chlorophenyl)

- 2

- aminobenzene

and 2

- chloronicotinic acid, were present in small amounts, accounting for <1% and <10% TRR, respectively.

HED has concluded that the parent compound, boscalid, is the sole residue of concern in primary

crop s for purposes of risk assessment and the tolerance expression. The cleavage products were not included, based on the limited cleavage which occurred, and the low levels of their ingestion expected from dietary and environmental sources.

4.1.2 Summary of Livestock Metabolism (860.1300)

PP#1F6313; DP# 278385; M. Nelson; 8/15/2003 HED MARC Decision Memo; DP# 286786; M. Nelson; 1/09/2003Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 11 of 29 T he nature of boscalid residues in livestock is adequately understood

, based upon acceptable 14 

### C metabolism studies conducted on lactating goat s and laying hens. In both goat s and hen s , parent boscalid, M510F01 (hydroxy metabolite), and M510F 02 (M510F01 glucuronide) w ere identified as the major residues, each with ≥10% TRR. N o amide bridge cleavage products were identified. Based on the structural similarity of boscalid and M510F 01, and the fact that the enzymatic hydrolysis step in the proposed enforcement method w ill release M510F 02 back to free M510F 01, HED concluded that the combined residues of parent boscalid , M510F 01 and

M510F02 are the residues of concern in livestock matrices for purposes of risk assessment and the tolerance expression.

4.1.3 Summary of Confined Rotational Crops (860.l850)

PP#1F6313; DP# 278385, M. Nelson, 8/15/03 HED MARC Decision Memo; DP# 286786; M. Nelson; 1/09/2003



### The nature of the residue in rotational crops is adequately understood and was summarized in a previous residue chem istry summary document. A total of 52.6

- 96.1% of the TRR was

identified in lettuce, radish roots and tops, and wheat forage and straw from the 30

- , 120

- , 270

- , and 365

- day PBIs. The parent, BAS 510 F

, was the major residue identified in these

commodities , accounting for 50.0

- 96.1% TRR (0.009

- 3.156 ppm). The glucoside metabolite M510F61 was identified in radish tops (all PBIs), radish roots (120

- and 365

- day PBIs only), wheat forage (all PBIs), and wheat straw (all PBIs); M510F61 accounted for 0.9

- 21.2% T RR (0.001

- 0.423 ppm). Unknown metabolites accounted for up to 22.7% TRR; however, individual peaks that were present at >10% TRR were each <0.04 ppm. Bound residues in certain samples of lettuce, radish tops and roots, and wheat forage and straw were ten tatively demonstrated to be due to the incorporation of radioactivity into protein, lignin, and cellulose at levels totaling up to 9.7% TRR. The remaining nonextractable residues were <0.05 ppm and were not further

characterized.

A total of 1.9

- 35.4% of the TRR was identified in wheat grain from the 30

- , 120

- , 270

- , and 365

- day PBIs. The parent, BAS 510 F, was the only compound identified in wheat grain at all PBIs, accounting for 9.6

- 35.4% TRR (0.008

- 0.028 ppm) in diphenyl

- label grain and 1.9

- 6.1% TRR
( 0.005

- 0.015 ppm) in pyridine

- label grain. Unknown metabolites accounted for  5.6% TRR
(  0.010 ppm). Bound radioactivity in wheat grain was tentatively demonstrated to be due to incorporation of radioactivity into starch, at 0.6

- 4.3% TRR (0.001

- 0.004 ppm) for the diphenyl label samples and 36.2

- 48.4% TRR (0.061

- 0.118 ppm) for the pyridine label samples, and protein, at 4.9

- 9.6% TRR (0.002

- 0.012 ppm) for the diphenyl label samples and 3.1

- 9.6% TRR (0.005

- 0.027 ppm) for the pyridine label samples. Nonextrac table residues were 30.3

- 71.6% TRR (0.007

- 0.174 ppm) in diphenyl

- label grain samples and 17.4

- 26.4% TRR (0.026

- 0.072 ppm) in pyridine

- label grain samples; these residues were not further characterized.

HED has concluded that the residue of concern in rot ated crops for purposes of risk assessment and the tolerance expression is parent compound.

4.1.4 Summary of Metabolites and Degradates

Appendix A lists the major metabolites and their chemical structures. Appendix B provides metabolic pathway diagrams for beans, goats, and hens.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 12 of 29 4. 2 Comparison of Metabolic Pathways

No significant metabolism of boscalid occurred in grapes or lettuce. Unchanged parent was the only component identified, and it accounted for 92

- 9 8% and 99% TRR in grapes and lettuce

, respectively. In bean plants boscalid metabolized slowly. Unchanged parent was up to 72% TRR in bean dry seeds and 99% TRR in bean plants. Cleavage products 1

- (chlorophenyl)

- 2

- aminobenz ene and 2

- chloronicotin ic acid were present in small amounts in various bean matrices, accounting for <1% and <10% TRR, respectively. These metabolites were also found

in the rat.

Metabolism in rotational crops was similar to primary crops. In the rotational crops lettuce,

r adish (roots, tops) and wheat (forage), boscalid was the major residue identified (50

- 96% TRR), with the glucoside metabolite, M510F61, accounting for 1

- 21% TRR. Only parent was found in wheat grain.

In the goat and hen metabolism studies, parent, M510F0 1 (hydroxy metabolite), and M51F510F02 (glucuronic acid metabolite of M510F01) were the major metabolites. Metabolites arising from the cleavage of the amide bond of boscalid were not identified in the livestock metabolism studies. In rats, cleavage of the amide bond appears to be very limited, based on <2% of the identified radioactivity in urine as the cleavage product 2

- chloronicotinic

acid.

4.3 Residues of Concern Summary and Rationale

MARC Decision Memo, D286786, TXR#0051452, M. Nelson, 01/09/03



### T able 4.3

. Summary of Metabolites and Degradates to be included in th e Risk

Assessment and Tolerance Expression

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Primary Crop Boscalid Boscalid

Rotational Crop Boscalid Boscalid

Livestock Ruminant Boscalid, M510F01,

M510F02 Boscalid, M510F01,

M510F02

Poultry Boscalid, M510F01,

M510F02 Boscalid, M510F01,

M510F02

Drinking Water Boscalid Not ApplicableBoscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 13 of 29 5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1 .1 Data Collection Methods
D373144, C. Olinger, 11/27/2007 4701401.der2 (dill) 4701402.der2 (chives) 47014803.der2 (basil)



### An adequate liquid chromatography/mass spectrometry/mass spectrometry ( LC/MS/MS ) method (BASF Method D9908) is also available for collecting residue data on plant commodities. Boscalid residues in all of the plant commodities associated with the current field trials were determined using this LC/MS/MS method. Using this method, residues are extracted with

methanol:wat er:2 N HCl (70:25:5; v:v:v) and centrifuged or filtered. Residues are then partitioned into cyclohexane, concentrated to dryness, and redissolved in buffered methanol:water (80:20, v:v). Residues are determined by LC/MS/MS using the m/z 343→307

transitio n for detecting and quantifying boscalid. Residues are quantified using an external

calibration curve of boscalid standards . The validated limit of quantitation is 0.05 ppm for boscalid in all commodities tested. In conjunction with the current field tr ials, the method was adequately validated using control samples of each plant matrix fortified with boscalid at levels ranging from 0.05 to 200 ppm.

Concurrent recoveries of boscalid averaged 83% with a standard deviation of 6% for fresh dill

and 80% with a standar d deviation of 8% for dill seed. Apparent residues of boscalid were less

than the lower level of method validation ( <LLMV ; <0.05 ppm) ppm in/on all control samples

.

Concurrent recoveries of boscalid averaged 82% with a standard deviation of 13% for fresh

basil. Concurrent recoveries of boscalid averaged 89% with a standard deviation of 10% for dried basil. Apparent residues of boscalid were <LLMV (<0.05 ppm) in/on a ll control samples. Concurrent recoveries bracketed residues found in treated samples.

Concurrent recoveries of boscalid from chives averaged 82% with a standard deviation of 12%. This high degree of variability, indicated by the high standard deviation comes from the disparity between recoveries at 0.05 and 5.0 ppm. The average recovery for chives fortified with boscalid at 0.05 ppm was 91% with a standard deviation of 10%, and the recovery for chives fortified at 5.0 ppm was 72% with a standard deviat ion of 4%. Apparent residues of boscalid were <0.05 ppm (<LLMV) in/on all control samples

. Concurrent recoveries did not bracket residues found in/on treated samples. However, there are adequate method recovery data from other leafy herbs (i.e., basil a nd dill) that were analyzed by the same method.

Conclusions.

The data collection method has been adequately validated via the concurrent recovery

determinations. The LLMV is 0.05 ppm for boscalid.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 14 of 29 5.1.2 Multi r esidue Methods (860.1360)

The data require ments for testing with the multiresidue method s in the Pesticide Analytical

M anual (PAM I) have been fulfilled and were discussed in the earlier petitions. Residues of

boscalid and its metabolite M510F01 were n ot adequately recovered using multiresidue me thod s

. Protocol A was not applicable. Protocol B was not applicable for boscalid and yielded

inconsistent recoveries of M510F01. Residues of boscalid and M510F01 had good responses

with GC/ electron capture detection ( ECD ) on a DB

- 1 column under Protocol C but neither analyte was recovered at ≥ 30% using Protocol D, E, and F.

Conclusions

.

The PAM multiresidue methods are not suitable for the determination of boscalid.

5.1 .3 Tolerance Enforcement Methods

PP#1F6313; D P# 278385, M. Nelson, 8/15/2003 DP# 284510; D. Swineford and E. Kolbe; 8/12/2003 (PMV memo )



### An adequate GC/MS method (Method D0008) is available for enforcing boscalid tolerances in plant commodities. The ACB/ BEAD concluded that the method is acceptable for enforcement purposes in plants without the need for an EPA validation (DP# 284510; D. Swineford and E. Kolbe, 8/12/2003, PMV memo ).

5.1.4 Submittal of Analytical Reference Standards (860. 1650)

Analytical reference standards for boscalid and its hydroxy metabolite are currently available in the EPA National Pesticide Standards Repository.

5.2 Storage Stability (860.1380)

DP# 322235, D. Dotson, 11/03/2005

MRID 47584402.der



### The collected samples of fresh dill and dill seed were stored frozen for 1 71 and 147 days, respectively, prior to analysis. Chive samples were stored frozen for 115 days prior to analysis. Basil samples were stored frozen for 172 days prior to analysis. No storage stability data were included in the study submission. However, previously submitted and reviewed data indicate that boscalid is stable under frozen storage conditions for at least 24 months in diverse crop matrices (DP# D322235, D. Dotson, 11/3/05). Adequate storage stability studies are available indicating that bos calid is relatively stable at ≤

- 20oC in fortified samples of cabbage ( high water

content ), canola seed ( high oil content ), peach ( high water content ), sugarbeet roots ( high starch

content ), peas ( high water content ), wheat grain ( high starch content ), whea t forage (foliage), and wheat straw (dry feed) for up to 24 months. Boscalid is stable at

- 5°C for up to 109 days (3.6 months) in orange fruit (high acid content) , dried pulp, juice and oil.

Conclusions

.

While no storage stability data were submitted wi th the present field trial studies, adequateBoscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 15 of 29 storage stability data exist to support the intervals of frozen storage of the samples.

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)
D373144, C. Olinger, 11/27/2007 4701401.der2 (dill) 4701402.der2 (chi ves) 47014803.der2 (basil)



### Herb subgroup 19A

Basil

IR

- 4 has submitted field trial data for boscalid on basil. Four field trials were conducted in North American Free Trade Agreement ( NAFTA ) Growing Zones 1 (NY, 1 trial), 3 (FL, 1 trial), 10 (CA, 1 trial), and 11 (WA, 1 trial) during the 2003 growing season. The test formulation used in all trials was BAS 510 UCF (Endura® Fungicide, EPA Reg. No. 7969

- 197), a water dispersible granule ( WDG ) f

ormulation containing 70% boscalid as the active ingredient. BAS 510 UCF was applied to basil as two directed foliar sprays at 0.30

- 0.32 lb ai/A/application for a total rate

of 0.60

- 0.63 lb ai/A (

~ 1x the maximum proposed seasonal rate of 0.58 lb ai/A). A pplications were made beginning when basil plants were at the vegetative/flowering stage and repeated on a

6

- to 8

- day retreatment interval using ground equipment (28

- 54 gal/A of spray volume) and did not include the use of a spray adjuvant.

Single contro l and duplicate treated samples of fresh basil were harvested from each test site at 0 and 3 days after treatment (DAT). Additional fresh basil samples were collected at 0 DAT and then dried according to simulated commercial practices in order to generate residue data for dried

basil.

Chives

IR

- 4 has submitted field trial data for boscalid on chives. Four field trials were conducted in NAFTA Growing Zones 2 (MD, 1 trial), 5 (OH, 1 trial), 10 (CA, 1 trial), and 11 (WA, 1 trial) during the 2003 growing season. The test formulation used in all trials was BAS 510 UCF (Endura® Fungicide, EPA Reg. No. 7969

- 197), a WDG formulation containing 70% boscalid as the active ingredient. BAS 510 UCF was applied to established chive plants as two directed foliar spr ays at 0.30

- 0.31 lb ai/A/application for a total rate of 0.60

- 0.62 lb ai/A (

~ 1x the maximum proposed seasonal rate of 0.58 lb ai/A). Applications were made beginning when chive plants were at the vegetative stage and repeated on a 6

- to 8

- day retreatment interval using ground equipment (24

- 50 gal/A of spray volume) and did not include the use of a spray adjuvant.

Single control and duplicate treated samples of fresh chives were harvested immediately from each trial site following the last treatment (0 DAT ).Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 16 of 29 Dill

IR

- 4 has submitted field trial data for boscalid on dill. Four field trials were conducted in NAFTA Growing Zones 2 (MD, 1 trial), 3 (FL, 1 trial), 10 (CA, 1 trial), and 11 (WA, 1 trial) during the 2003 growing season. The test formulation us ed in all trials was BAS 510 UCF (Endura® Fungicide, EPA Reg. No. 7969

- 197), a WDG formulation containing 70% boscalid as the active ingredient. BAS 510 UCF was applied to dill plants as two directed foliar sprays at

0.29

- 0.31 lb ai/A/application for a to tal rate of 0.59

- 0.62 lb ai/A (

~ 1x the maximum proposed seasonal rate of 0.58 lb ai/A). Applications were made beginning when dill plants were at the vegetative growth stage through seed production; the retreatment intervals were 6 to 8 days. Foliar spra ys were made using ground equipment (28

- 62 gal/A of spray volume) and did not include the use of a spray adjuvant.

Single control and duplicate treated samples of fresh dill and dill seeds were harvested immediately from each trial site following the last treatment (0 DAT).

A summary of residue data from the field trials is presented in Table 5.3.1.

Table 5.3.1. Summary of Residue Data from Field Trials with Boscalid

Crop Matrix Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels of Boscalid (ppm) 1

n Min. Max. HAFT Median (STMdR) Mean

(STMR) Std. Dev.

BASIL Proposed use pattern: Two foliar sprays at 0. 29 lb ai/A/application for a seasonal rate of 0. 58 lb ai/A with a 0

- day PHI.

Fresh Basil 0.60

- 0.63 0 8 11.3 30.6 24.1 15.5 17.7 7.2

3

- 4 8 2.0 16.0 13.5 9.3 8.7 4.9

Dried Basil 0 4 60.6 142.0 142.0 117.7 109.5 36 CHIVES. Proposed use pattern: Two foliar sprays at 0. 29 lb ai/A/application for a seasonal rate of 0. 58 lb ai/A with a 0

- day PHI.

Chives 0.60

- 0.62 0 8 1.6 13.2 12.8 11.6 9.5 4.8 DILL. Proposed use pattern: Two foliar sprays at 0. 29 lb ai/A/application for a seasonal rate of 0. 58 lb ai/A with a 0

- day PHI.

Fresh Dill (dillweed) 0.60

- 0.61 0 8 5.88 29.2 28.6 15.6 16.3 8.5

Dill Seed 0.59

- 0.62 0 6 5.70 42.2 41.2 10.6 22.5 16

Dill Seed 0.91 0 2 117 129 123 N/A N/A N/A

1 n = number of samples, typically 2X number of trials. Min = lowest replicate sample value. Max = highest replicate sample value. HAFT = highest average field trial. STMdR = median of average field trials. Mean = mean of average field trials.



### Conclusions

.

Studies reflect the proposed use pattern. The number of trials and geographic distribution are acceptable. The analytical method used is adequate for determination of the residue of concern, and the samples were stored frozen for intervals supported by the storage stability results.

5.3.2 Field Rotational Crops (860.1900 )

PP#1F6313; DP# 278385, M. Nelson, 8/15/2003 DP# 322235, D. Dotson, 11/03/2005
DP# 323288, D. S oderberg, 6/14/2007



### Adequate limited and extensive field rotational crop studies are available supporting the existing tolerances for indirect residues in rotational crops. These data support the label

- specific plant

-Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 17 of 29 back interval of 14 days for crops without boscalid uses. No additional rotational crop data are required for purposes of this petition.

Conclusion : There are currently no deficiencies pertaining to rotational crops.

5.3.3 Processed Food and Feed (86 0.1520)
D373144, C. Olinger, 11/27/2007 47014803.der2 (basil)



### Basil from each of the four field trials was dried.

Table 5.3.3.1 Residue Data from the Basil Processing Study with Boscalid

RAC (trial #) Processed Commodity Total Rate

lb ai/A PHI (day) Residues (ppm) Processing Factor

Boscalid Boscalid

Fresh

Basil (NY17) RAC

(prior to processing) 0.63 0 12.6

-

Dried Basil 60.6 4.8

Fresh Basil (FL55) RAC

(prior to processing) 0.61 0 21.9

-

Dried Basil 142 6.5

Fresh Basil (CA125) RAC

(prior to processing) 0.60 0 24.1

-

Dried Basil 129 5.4

Fresh Basil (WA18) RAC

(prior to processing) 0.61 0 12.3

-

Dried Basil 106 8.6



### The median processing factor for the conversion of fresh basil to dry basil is 6.0x.

Conclusion:

The four processing studies conducted for the production of dried basil are adequate to estimate a processing factor for the boscalid residue. In each of the trials, the fresh basil contained quantifiable residues of boscalid.

5.3.4 Meat, Milk, Poultry and Eggs ( 860.1480)

PP#1F6313; DP# 278385, M. Nelson, 8/15/2003
DP# 322235; D. Dotson, 11/03/2005 45405110.der (cattle feeding study ) 45643801.der (poultry feeding study ) 47584403.der (cattle feeding study) DP# 364447; A. Acierto, 10/16/2009 47584403.der (cattle feeding study)



### There are no proposed uses that are relevant to this guideline topic. There are no feed items associated with dill seed and the herb subgroup. Therefore

, the previous livestock dietary intake calculations and resulting tolerance recommend ations are not changed.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 18 of 29 5.3. 5

. Food Handling (860.1460)

This guideline requirement is not relevant to the current petition as there are no food

- handling uses being proposed for boscalid

.

5.3. 6 Water, Fish, and Irrigated Crops (860.1400)

T his guideline requirement is not relevant to the current petition as there are no aquatic uses being proposed for pyraclostrobin.

6.0 Tolerance Derivation

The Organization for Economic Cooperation and Development (OECD) calculation procedure

was used to determine tolerance estimates for the relevant commodities. All field trial results were above the LOQ (0.05 ppm). See Appendix D

.

The tolerance estimates for the herbs fresh basil, fresh dil l weed, and fresh chives are 60 ppm, 60 ppm, and 30 ppm, respectively. The tolerance estimate for dried basil is 150 ppm ( 24.1 ppm HAFT X 6. 0 processing factor = 145 ppm , rounded to 150 ppm ). The recommended tolerance for the herb subgroup 19A, which encompasses both fresh and dried herbs, is 150 ppm.

The tolerance estimate for dill seed, a spice, is 100 ppm.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 19 of 29 Appendix A. Tabular Summary of MetabolitesBoscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 20 of 29Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 21 of 29Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 22 of 29Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 23 of 29 Appendix B. Metabolic Pathways

Metabolic pathway in beansBoscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 24 of 29 Metabolic pathway in the goatBoscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 25 of 29 Metabolic pathway in the henBoscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 26 of 29 Appendix C . International Residue Limits Table



## Boscalid ( 128008; 06/30/2014 )

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 Codex 3

40 CFR §180.589. Plant commodities:

boscalid, 3

- pyridinecarboxamide, 2

- chloro

- N

- (4 ′

- chloro[1,1'

- biphenyl]

- 2

- yl), Plant commodities:

2

- chloro

- N

- (4'

- chloro[1,1'

- biphenyl]

- 2

- yl)

- 3

- pyridinecarbox

amide - Plant commodities:

boscalid.



### Commodity 1 

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

US Canada Mexico 2 

### Codex 3

Herbs subgroup 19A
(fresh and dried) 150 None None

Dill

, seed 100 None None
Nut, tree, group 14

- 12 0.70 0.7 0.05 (*)
Fruit, stone, group 12

- 12 3.5 1.7 3

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 quan titation; 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 n ot been finalized by the CCPR and the CAC.Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 27 of 29 A ppendix D

. OECD MRL Calculation Procedure Inputs/Outputs

Compound Boscalid Boscalid Boscalid Boscalid
Crop

Dill Seed Dillweed Basil (fresh) Chives Region / Country US US US US

GAP 2 X0.3, 0 day 2X0.3, 0 d 2X0.3, 0 d 2X0.3, 0 d

Total n umber of data (n) 3 4 4 4 Percentage of

censored data 0% 0% 0% 0%

Number of non

censored data 3 4 4 4

Lowest residue 5.830 8.110 12.300 1.850 Highest residue 41.200 28.600 24.100 12.700

Median residue 20.600 14.300 17.250 11.750

Mean 22.543 16.328 17.725 9.513

Standard deviation (SD) 17.765 8.854 6.158 5.164

Correction factor for censoring (CF) 1.000 1.000 1.000 1.000

Proposed MRL

estimate

- Highest residue 41.200 28.600 24.100 12.700

- Mean + 4 SD 93.603 51.744 42.357 30.170

- CF x 3 Mean 67.630 48.983 53.175 28.538

Unrounded MRL 93.603 51.744 53.175 30.170

Rounded MRL 100 60 60 30

High

uncertaint
y of MRL

estimate

due to

small

dataset. High

uncertaint
y of MRL

estimate

due to

small

dataset. High

uncertaint

y of MRL

estimate

due to

small

dataset. High

uncertaint
y of MRL

estimate

due to

small

dataset.

Residues (mg/kg) Residues

(mg/kg) Residues

(mg/kg) Residues

(mg/kg)

20.600 28.600 12.600 11.000

41.200 12.200 21.900 12.500

5.830 16.400 24.100 12.700

8.110 12.300 1.850Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 28 of 29 References:

DP Number: 410742 Subject: PP# 2E8068

. Boscalid; Petition for the Establishment of Permanent Tolerances

and Registration for Use on Belgium Endive, Persimmon, and Globe Artichoke. Request for Crop Group Expansions/Revisions for Bulb Vegetable Group 3

- 07, Fruiting Vegetable 8

- 10, Citrus Fruit G roup 10

- 10, Pome Fruit Group 11

- 10, Berry Subgroups 13

- 07A, B, F, and G, and Oilseed Group 20. Summary of Analytical Chemistry and Residue Data

From: S. F unk

To: B. Madden/A. Ertman

Dated: 06/20/2013

MRIDs: 48897401, 48897402, 48897403

DP Numbers : 27838 5, 282532, 286787, 287829 Subject: PP#1F06313. BAS 510 F (Common Name: Boscalid), New Fungicide Active

Ingredient. Residue Chemistry Summary Document.

From: M. Nelson

To: M. Rodriquez/C. Giles

- Parker

Dated: 08/15/ 20 03

MRIDs: 4540502 1

- 45405028, 45405101

- 45405128, 45405202

- 45405204, 45623401

-

45623413, and 45643801

DP Number : 322235 Subject: PP#s 1F6313, 3E6791, 4F6875, and 5E6933: Boscalid, Registrant’s Response to

Deficiencies Cited in Tolerance Petition 1F6313. Summary of Analytical Chemistry and Residue Data for Rotational Root Crops, Direct Uses on Celery, Spinach, Bananas, Strawberries , Almonds, and Potatoes, and Seed Treatment Uses on Bulb Vegetables, Brassica Leafy Vegetables, Legume Vegetables, Peanuts, and Sunflowers.

From: D. Dotson

To: J. Bazuin/T. Kish

Dated: 11/3/ 20 05

MRIDs: 46145101, 46145102, 46160103, 46210606, and 46351401

- 4 6351405Boscalid Summary of Analytical Chemistry and Residue Data Barcode D 421150



### Page 29 of 29 DP Number : 323288 Subject: Boscalid. Petition for a Tolerance for Belgian Endive; Petition for Increased

Tolerances on Strawberry and the Berries Crop Group; Submission of Requested Field Trial Data on Cucumber, Mustard Gree ns and Sunflower; and Supplemental Field Trial Data on Fruiting Vegetables, Radishes, Spearmint, Peppermint, Grapes, and Stone Fruits; and Submission of Field Trials and a Processing Study for Cotton. Summary of Analytical Chemistry and Residue Data

. From : D. Soderberg

To: C. Swartz

Dated: 6/04/ 20 07

MRIDs: 46512002, 46512003, 46637701, 46665501, 46665502, 46665503, 46665504,

46665505, 46665506, 46713801, 46685902, 46685901