### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHIN G TON

, D

. C. 20460



### MEMORANDUM

Date: 7111 / 2014 OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION



### Sub j ect: Ha la uxi fe n-Methyl. Petition for the Sectio n 3 Regist r at i on and t h e Estab lislun e nt of
Tolerances on Wheat

, Barle y , and Tritica l e. Summary of Analytical Chemistry and
Residue Data

PC Code: 11750 I
Dec i sion Nos .: 470169

Petition N o .: 2E80 86
Risk Assessment Type: NA
TXRNo.: NA
MRID Nos.: 4 85577 89- 48557796, 48557 802

, 48557807

, 48557812,48557813,48557865

, 4855 7 898

, 48901101,49065802

, 49065803 DPBarcode: 0 4 1 6127 Registration Nos.: 62719

- AAE, AAG, AAN, AAR

, AAU Regulatory A c t ion : Section 3 Re g istrati on CaseNo.: N A
CAS No.: 943831-98-9
40CFR: NA

Fro m : 

### Douglas A. 

### Dot son , Ph

. D

. , Che mi st 

# IJ.**~~** RA BII
Health Effec ts Division ( 750 9P)

Through : 

### P

. Y vonne Barnes

, Chemist 

# -j?**~ '"$** **:> _**  

# L

Michae l Doherty

, Ph. D., Sen i or C h emist

### ~**~~ q**  HED C h em i stry Sc i e n ce Advisory Council (ChemSAC)

Hea l th Effects D ivis ion (7509P)

To: 

### Maggie Rudick/Kable Bo D avis, PM Team 25
Herbicide Branch Registrat i o n D iv i s i o n (7505P)Halauxifen-Methyl Summary of Analytica l Chemistry and Residue Data D P Numbe r 0416127

Tab le of Contents

1.0 Executive Summary

.. ... . ..... . ................... . .. . .. .. ... . ................... . .......................... . ........... . .... 4

2

. 0 Regulatory Recommendations

............................................ . ..................... . ...................... 5
2.1 Data Deficiencies / Data Needs

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

2

. 2 Tolerance Considerat i ons

. .. .. .. .. . ... . ... . .. .. .. . ... . ... . .. .. ... . .. .. .. .. .. ... . .. ... . ... . ... . ... .. ... . ... .. ... . ...... 5
2.2.1 Analytical Enforcement Method

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

2.2

. 2 Recommended Tolerances

.. ... . .. .. .......... .. . .. ............ . . . ................ . ................ . 7
2.2.3 Revisions to Proposed To l erances

. ... .. . .. .. .. ... . .. .. .. .. ... . ....... .. .. .. .. .. ... .. .. .. .. ... .. 8
2.2.4 International Harmonization

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

2.3 L abe l Recommendations

.. . .. .. .. . ... . .. .. ...... . ... . ... . .. .. ... . .. . ... .. .. .. .. . ... . ... . .... . ... . ..................... 

### 8

3.0 Introduction

. .. .. . ... . .. . .. . ... . .. . ........................ . ... . .... .... . ...................... . ..... . .. ... ... . .. .. .... . .. .. .. .... . . 9
3.1 Chemica l I dentity

. . ... . ... . .. .. .. . ... . .. . ... . ... . ... . .. .. ...... . ... . ... . ... .. .. .. ....................................... . . 9
3.2 Physical/Chemical Characteristics

........ . ... . ... . .. .. ... . ... . ... . ... . ... . ... . ... . ... . .... . ... . ... .. ... . ...... 10
3.3 Pesticide Use Pattern/Directions for Use (860. 1 200)

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

4

. 0 Metabolite/Degradate Residue Profile

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

4.1 Nature ofthe Residue

... . . .. .. .. .. . ... . .. .. .. .. .. . ... .. .. . ... . ... . .. .. .. . ... . ......... . ............ . ........ . ....... . . 1 1

4.1.1 Summary of Plant Metabolism (860.1300)

. . ... .. .. .. .. .. .. .. .. ... .. . .. .. ... . ............ 12
4

. 1.2 Summary of Confmed Rotational Crops (860. 1 850)

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

4.1.3 Summary of L i vestock Metabolism (860.1300)

.. . .. . .................. . .............. 1 5

4

. 1. 4 Summary of Metabolites a n d Degradates

. .. . ... . .. ... .. . ..... .. . . ........................ 16
4.2 Compar i son of Metabolic Pathways

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

4 .3 Residues of Concern Summary and Rationale

............ . ...... . .. .. ... . ............................... 17
5

. 0 Residue Profile

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

5.1 Residue Ana l ytical Methods (860.1340)

............... . .... . ............................. . ... . ... .. ... .. .. 19
5.1.1 Data Collection Met h ods

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

5.1.2 Multi-Residue Methods (860.1360)

.. .. . ... .. .. .. ... . ........................................ 21
5. 1. 3 Tolerance Enforcement Methods

......... . . . ........ . ... . ....... .. . . .. .. .. .. .. .... . ........... 22

5.1.4 Submittal of Analyt i ca l Reference Stan d ards (860.1650)

........... .. .. .. ... .. .. 23
5. 1 .5 Storage Stabi l ity

... . ................. . .................... .. .. .. .. .. .. .. .. . . .. .. ........................ 24

5.2 Residue Data

.......... . ............ . .. .. . .. .. .. .. .. .. .. . ... . .. .. .. ... . .. . ... . ................. . ....... . ....... . .. .. .... . .. 25
5.2.1 Crop Fie l d Trials (860.1500)

............ . ......... . ... . ... .. . ... .. .. .. .. .... . ....... . ........... 25

5 .2.2 Field Rotational Crops (860

. 1900)

. .. .. . ... .. ......... . . . .................................... 28
5.2

. 3 Processed Food and Feed (860.1520)

..................... .. .. . .. .. ... . ... .. .. .. ... .. ....... 28
5.2.4 Mea t

, Milk, Poultry, and Eggs (860

. 1 480)

.................................. . ... . .. .. .... 30

5

. 2

. 4

. 1 Dietary Burden

....... . .... . .. . ... . .. .. .. .. .. . ... .. .. . .......................... . ...... . .. ... .. . 30

5

. 2.4

. 2 Estimat ed Secondary Residues in Livestock

. . ... . .............................. 31
5.2.5 Food Hand li ng (860

. 1 4 60)

........ . ............. . .. . ....... . ... . . .. . .. .. ... . . . . . ............... . .. 35

5.2.6 Water

, Fish, and I rrigated Crops (860.1400)

................ . . . ...... .. ... . ... .. ... . .... 35

6

. 0 Tolerance Derivation

.......... . ...... . .. .. .. .. .. . ... . .................... . ......................... . ... . ... .. ........ . .... 35

7.0 ChemSAC Reference

................................ . ... . .. .. .. . ... . ... . ... . ... . ................. . .......... . ... .. .. ... . .. 35
Attachments

.. .. .. . ... . ... . .. . ............. . ...................... . ....... . ... . ... . ... . ... . .. .. .. . ............................... 36

I. Summary of Submitted Res i due Chemistry Studies

............... .. ....... ... .. .. .. .. .. .. ... .. ... .. .. . 36
2. NAF T A Field Trial Geographic Represen t ation

... .. .. . ... .. .. . ... . ... . ... .. ................. . .......... . 38


### 3. Field Trial Data 

### and OECD MRL Calculator Outputs

..................... .. .. .. .. .. .. .. .. .. ... .. ... . 40
4. Internationa l Residue Limits Table

................... .. .. . ... .. .. .. .. . ... . .... . ................. . ... . .......... . 42

Page 2 of 56Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 3 of 56 5

. Summary Tabl e of Important Metabolites and Degradates

................................ ......... 4 3
6

. Metabolic Pathways

................................ ................................ ................................ ..... 47
6.a. Wheat

................................ ................................ ................................ ................ 47
6.b. Turnips

................................ ................................ ................................ .............. 48
6.c. Goats

................................ ................................ ................................ ................. 49
6.d. Hens

................................ ................................ ................................ .................. 50
6.e. Rats

................................ ................................ ................................ .................... 51
6.f. Proposed Enviro nmental Transformation Scheme

................................ ............ 52
7

. Chemical Structures of Important Metabolites

................................ ............................ 53Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 4 of 56 Background

Halauxifen

- methyl is a post

- emergent herbicide developed for control of a broad spectrum of broadleaf and sedge weeds. It can also be used for the control of some key grass weed species in cereal crops as well as in range and pasture. The pet itioner for this new active ingredient is Dow AgroSciences, LLC. The science reviews are being performed joint ly between USEPA, Canada’s Pest Management Regulatory Agency (PMRA)

, and Australia’s Pesticides and Veterinary Medicines Authority (APVMA ).

Halauxifen

- methyl is proposed for use on wheat, barley, and triticale

. Four agricultural products are proposed for use on the se crops: GF

- 2685, GF

- 2686, GF

- 2687, and GF

- 2688. GF

- 2685, 2686, and 2687 are water dispersible granule (WG) formulations while GF

- 2688 is an
emulsifiable concentrate. These products contain the single active ingredient, halauxifen

- methyl,
or a combination of halauxifen

- methyl and either florasulam or fluroxypyr. GF

- 2685 contains
10.4% halauxifen

- methyl, GF

- 2686 contains 10% halauxifen

- methyl and 10% florasulam, GF

2686 contains 20.9% halauxifen

- methyl and 20% florasulam, and GF

- 2688 contains 1.6%
halauxifen

- methyl and 34.9% fluroxypyr. T his residue chemistry summary document addresses
halauxifen

- methyl o nly.

1.0 Executive Summary

Halauxifen

- methyl is a new active ingredient that the petitioner

, Dow AgroSciences LLC

, is proposing for use on wheat, barley, and triticale . In support of this tolerance petition, the petitioner submitted the results of met abolism studies on plants and livestock , feeding studies, analytical method studies for both plant and livestock commodities, storage stability studies, crop field trial studies, processing studies, and a confined rotational crop stud y . HED has reviewed

t hese studies as part of a joint review with Canada’s PMRA and Australia’s APVMA

.

The plant and livestock metabolism studies are adequate for determination of the residues of concern in plants and livestock for both tolerance enforcement and risk assessmen t for the purposes of the current tolerance petition

. HED has determined that the residue of concern in primary crops and rotational crops for both tolerance enforcement and risk assessment is parent halauxifen

- methyl only. The residue of concern in ruminants and poultry for both tolerance
enforcement and risk assessment is the metabolite X11449757 ( 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- hydroxyphenyl)

- pyridine

- 2

- carboxylic acid )

.

A n a dequate analytical method is av ailable for enforcement of the tolerances in plant

c ommodities. The tolerance enforcement method is a liquid chromatography with tandem mass spectroscopy ( LC

- MS/MS ) method that w as adequately validated. It has a limit of quantitation of 0.01 ppm.

The pe titioner submitted adequate use directions for the end use products. The petitioner also submitted adequate field trial and processing data for wheat and barley. Adequate numbers of trials were performed in the recommended North American Free Trade Agree ment (NAFTA) growing zones, and the studies are supported by adequate storage stability and analyticalHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 5 of 56 methods data. The Organization for Economic Co

- operation and Development ( OECD ) maximum residue limit ( MRL ) calculation procedures were used to determin e the recommended
tolerances.

The petitioner submitted an adequate cattle feeding study that can be used to determine the need
for tolerances for ruminant commodities. H E D has determined that there is no reasonable expectation of finite residues in rumin ant or poultry commodities. As a result, tolerances are not
needed for them.

2.0 R egulatory R ecommendations

Provided the submitted Section F is revised as noted below, there are no residue chemistry issues that would preclude granting the requested Section 3 registration for halauxifen

- methyl and the recommended tolerances on the proposed commodities as listed in Table 1

. The tolerance expression for plant commodities is given in the Recommended Tolerances section of this
docu ment.

2.1 Data Deficiencies/D ata Needs

The petitioner should submit a revised Section F in which the recommended tolerances and correct commodity definitions listed in Table 1 are proposed. There are no residue chemistry
data deficiencie s associated with this tolerance petition.

2.2 Tolerance Considerations

2.2.1 Analytical Enforcement Method s

Plant Commod ity Enforcement Method

As the analytical enforcement method for halauxifen

- methyl in plant matrices

, t he petitioner proposed the method in Report Number 110004 . With this method, residues of halauxifen

methyl and XDE

- 729 acid are extracted with acetonitrile:water (80:20, v/v) . Extracted residues then undergo clean

- up by solid

- phase extraction and analysis by L C

- MS/MS. Ion transitions for
h alauxifen

- methyl are 345/250 (quantitation) and 345/235 (confirmation). Ion transitions for
XDE

- 729 acid are 331/250 (quantitation) and 331/285 (confirmation).

HED has determined that this method is acceptable as an analytical enforcement method , as defined in Standard Operating Procedure (SOP) No. ACB

- 019 (9/15/2008). The method is considered to be fully validated for data generation and monitoring of halauxifen

- methyl residues in the full range of plant matrices : wet, dry, oil, and acid

. Two ion transitions are available for parent halauxifen

- methyl

. The LOQ of the method was determin ed to be 0.010 ppm for wheat and barley

. The petitioner submitted an acceptable ILV . Acceptable radiovalidation data were submitted with the data collection method . The enforcement m ethod will be forwarded to FDA
for inclusion in PAM II. The method can also be obtained from the Analytical Chemistry Branch of the Biological and Economic Analysis Division (ACB/BEAD).Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 6 of 56 FDA Multi

- Residue Method for Plant Commodities

The FDA’s Pesticide Analytical Manual’s multiresidue methods were evaluated for their suitability for the analysis of halauxifen

- methyl and its metabolite XDE

- 729 acid. Protocol A was not suitable because of poor sensitivity, and Protocol C was not suitab le because of degradation in the gas chromatography detector. Without an appropriate determinative step from
Protocols A and C, the remaining testing by Protocols B, D, E, and F was suspended, as per the PAM protocol. As a result, t he FDA multiresidue te st procedures are not suitable for the regulatory analysis of halauxifen

- methyl and XDE

- 729 acid

.

QuEChERS M ultiresidue M ethod for Plant Commodities

Th e QuEChERS multiresidue method was evaluated for the quantitative determination of
residues of halauxif

en

- methyl and XDE

- 729 acid in agricultural commodities representative of
the four OECD crop types: wet crop, dry crop, oily crop, and acidic crop . Residues of
halauxifen

- methyl and XDE

- 729 acid were extracted from the sample matrices by shaking with

an a cetonitrile/water solution. After addition of a salt mixture consisting of magnesium sulfate, sodium chloride, trisodium citrate dihydrate, and disodium hydrogen citrate sesquihydrate, the extract was shaken. Minor modifications to the procedure were mad e for acidic samples (e.g., lemons) to make the pH less acidic. After centrifugation, an aliquot of the acetonitrile extract was purified by freezing out and/or dispersive solid phase extraction using a primary secondary amine sorbent. Subsequently, the purified aliquot was diluted to volume with aqueous 0.1% formic acid. After preparation, the samples were analyzed by liquid chromatography using a Synergi Hydro

- RP C 18 

### column coupled with positive

- ion electrospray tandem mass spectrometry (LC/MS/MS), mon itoring two MS/MS transitions characteristic of each analyte. Ion transitions
for halauxifen

- methyl are 345/250 (quantitation) and 345/207 (confirmation). Ion transitions for
XDE

- 729 acid are 331/250 (quantitation) and 331/207 (confirmation). The method was validated over the concentration range of 0.01

- 0.10 mg/kg with a validated limit of quantitation (LOQ) of 0.01 mg/kg. Recoveries were acceptable. The method is adequate for determination
of residues of halauxifen

- methyl and XDE

- 729 acid in the four types of crops tested.

Livestock Commodity Enforcement Method

Dow AgroSciences proposed the m ethod described in Report 110505 as the analytical
enforcement method for halauxifen

- methyl and XDE

- 729 acid in livestock matrices. However,
HED has determined that the residue of concern in livestock commodities is the metabolite
X11449757. Based on the available data for residues in livestock feedstuffs associated with this petition, quantifiable residues in livestock matrices are not expected, and a validated livestock enforcement method is not necessary at this time. In the cattle feeding study, samples of cattle commodities were analyzed using a modification of the proposed enforcement method. In the
event that tolerances are needed for livestock commodities in the future, the petitioner will need to submit an adequate enforcement method for residues of X11449757 in livestock commodities
and an ILV for t he method

.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 7 of 56 2.2.2 Recommended Tolerances

HED recommends that 40CFR be amended by establishing tolerances for the plant commodities
listed in the table below. T he residue definitions for plant and livestock commodities are different, as a result, HED has prepared two separate tolerance summary tables for them. For plant commodities, the tolerances should be established as follows: Tolerances are established
for residues of halauxifen

- methyl , 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 halauxifen

- methyl ( methyl ( 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- methoxyphenyl)

- 2

- pyridinecarboxylate )

.

Table 1. Tolerance Summary for Halauxifen

- methyl

Commodity as Proposed by
Petitioner Proposed
Tolerance (ppm) Recom

mended
Tolerance (ppm) Comments

(correct commodity definition)

Plant Commodity Tolerances barley, grain 0.01 0.01 Barley, grain barley, hay 0.01 0.01 Barley, hay barley, straw 0.01 0.01 Barley, straw wheat, forage 0.5 0.5 0 Wheat, forage wheat, grain 0.01 0.01 Wheat, grain wheat, hay 0.04 0.03 Wheat, hay wheat, straw 0.015 0.015 Wheat, straw



### Dow AgroSciences did not propose a tolerance for triticale, and does not need to because a
tolerance for wheat automatically applies to triticale (40 CFR §180.1(g)).

Tolerances are not needed f or livestock commodities . The tolerances that the petitioner proposed are listed in the following table

.

Table 2. Tolerance Summary for Halauxifen

- methyl

Commodity Proposed
Tolerance (ppm) Recom

mended
Tolerance (ppm) Comments

(correct commodity definition)

c attle, f at 0.01 None

c attle, me at 0.01 None

c attle, meat byproducts 0.01 None goat, fat 0.01 None
goat, meat 0.01 None
goat, meat byproducts 0.01 None horse, fat 0.01 None horse, meat 0.01 None horse, meat byproducts 0.01 None

m ilk 0.01 NoneHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 8 of 56 Table 2. Tolerance Summary for Halauxifen

- methyl

Commodity Proposed
Tolerance (ppm) Recom

mended
Tolerance (ppm) Comments

(correct commodity definition)

s heep, fat 0.01 None

s heep, meat 0.01 None

s heep, meat byproducts 0.01 None



### 2.2.3 Revisions to P roposed Tolerances

As can be seen in Table 1, above, the only recommended tolerance that is different from the proposed tolerance is that for wheat hay. The petitioner proposed a tolerance of 0.04 ppm, whereas HED determined that a tolerance of 0.03 ppm is appropriate. When the petitioner determined the proposed tolerances, i t included the metabolites XDE

- 729 acid as a residue of concern. HED subsequently determined t hat this metabolite is not a residue of concern for
tolerance enforcement. The petitioner should submit a revised Section F in which a tolerance of 0.03 ppm is proposed for wheat, hay.

2.2.4 International Harmonization

Halauxifen

- methyl is a new active ingredient, and no MRLs have been established by Codex, Canada, or Mexico. Th e U.S., Canada, and Australia , all agreed to use the OECD MRL
calculat ion procedures for this tolerance petition. In addition, the three countries are in

agreem ent with respect to the residues of concern for tolerance enforcement. The residue of concern in plant commodities is parent halauxifen

- methyl only. The residue of concern in
livestock commodities is the metabolite X11449757.

T he tolerances/ MRLs that ar e being recommended by the U.S. and Canada are harmonized to the extent possible . In the cases where tolerances/ MRLs are not being harmonized, it i s because of policy differences in the way the two countries establish tolerances/ MRLs. The only MRLs that are not being harmonized are those for livestock feed items and livestock c ommodities. Canada
does not establish MRLs for livestock feed items, whereas the U.S. does establish tolerances

. The U.S. is establishing tolerances for wheat forage, hay, and str aw , as well as for barley hay and

straw. On the other hand, the U.S. generally does not establish tolerances for livestock commodities when there is no reasonable expectation of finite residues. Canada establishes LOQ
MRL s in these situations. As a result, Canada is establishing LOQ MRL s for ruminant, poultry

, and swine commodities, whereas the U.S. is not establishing tolerances

.

2.3 Label Recommendations

The proposed labels specify the single application rates and th e maximum seasonal application

rate s

. However, the labels do not specify the maximum number of applications that may be made per season. On each of the labels, the petitioner needs to specify the maximum number of applications that may be made per growin g season. Some of the end

- use products proposed forHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 9 of 56 registration contain multiple active ingredients. For those products, RD should ensure that the use restrictions on the proposed labels are in accord with any restrictions associated with the co

formula ted active ingredients.

3.0 Introduction

3.1 Chemical Identity

Table 3 . Nomenclature and Identification Information for Halauxifen

- Methyl 

### Active Ingredient

Common Name Halauxifen

- methyl Company Experimental Name XDE

- 729 methyl or XDE

- 729 methyl ester Company Experimental Number X11393728
IUPAC Name Methyl 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- methoxyphenyl)pyridine

- 2

- carboxylate
Molecular Formula C 14 

### H 11 

### O 3 

### N 2 

### Cl 2 

### F Molecular Weight 345.16
CAS Name M ethyl 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- methoxyphenyl)

- 2

- pyridinecarboxylate
CAS Number 943831

- 98

- 9Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 10 of 56 3.2 Physical/Chemical Characteristics

Table 4 . Physicochemical Properties of the Technical Grade Test Compound

Parameter Value for
Halauxifen

- methyl Value for
XDE

- 729 Acid (X11393729) Reference

Water solubility pH 5 pH 7 pH 9
unbuffered mg/L at 20°C
1.66
1.67
1.69
1.83 at 20°C 102 mg/L 3.07 g/L 46.1 g/L 84.0 mg/L Tolerance

Petition
2E8086

Octanol/water partition
coefficient at 20°C Log K OW Log K OW

pH 5 buffer solution 3.75 0.42 pH 7 buffer solution 3.76

- 0.83 pH 9 buffer solution 3.92

- 1.01 Vapor Pressure 5.9 x 10

- 9 Pa at 20°C (4.4 x 10

- 11 mmHg)
1.5 x 10

- 8 Pa at 25°C (1.1 x 10

- 10 mmHg) 2 x 10

- 5 Pa at 20°C (1.5 x 10

- 7 mmHg)
3 x 10

- 5 Pa at 25°C (2.3 x 10

- 7 mmHg) Organic solvent solubility g/L at 20°C g/L at 20°C

methanol 38.1 4.2

acetone >250 4.4 ethyl acetate 129 1.2

n

- octanol 9.83 0.43 Melting point 146°C not available pH 6.24 not available Dissociation constant (pK
a ) 2.84 @ 20°C 5.11 @ 21.9°C



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

Halauxifen

- m ethyl is a post

- emergent herbicide developed for control of a broad spectrum of broadleaf and sedge weeds . The herbicide is to be applied in the spring or fall early postemergence to the main flush of actively growing weeds in the 2

- to 4

- leaf stage or less than 4 inches. Only weeds that have emerged at the time of application will be controlled.

The labe ls do not specify the maximum number of applications that may be made. The recommended single application rate is approximately 0.00 5 lb ai/A . For GF

- 2685 , the maximum seasonal application rate is 0.00 91 lb ai/A. These application rates indicate that th e total number of applications of GF

- 2685 should not exceed two.

The PHI listed on all four labels is 60 days. The labels also state that the product should not be applied closer than 21 days before the cutting of hay. The label for GF

- 2685 states that livestock may be grazed 1 day following application. The only active ingredient in this product isHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 11 of 56 halauxifen

- methyl. The labels for GF

- 2686, GF

- 2687, and GF

- 2688 state that livestock may be grazed 7 days following application. These products contain ei ther florasulam or fluroxypyr in
addition to halauxifen

- methyl.

The GF

- 2685, 2686, 2687, and 2688 labels all give a rotation interval of 0 months for wheat, barley, and triticale. The labels state that the following crops have a 3

- month rotation interval: camalina, canola, oats, field corn, popcorn, seed corn, sweet corn, millet, mustard, rye, sorghum, and grasses. A 9

- month rotation interval is listed for alfalfa, cotton, chickpea, dry bean, peas (dry and succulent), flax, peanut, safflower, so ybean, and sunflower. Other crops not listed on
the label have a 15

- month rotation interval.

Table 5

. Proposed Uses of Halauxifen

- Methyl on Wheat, Barley, and Triticale

Applic. Timing, Type, and Equip. a Formulation (EPA

Reg. No.) b Applic ation Rate

(lb a i /A) Max No.

Applic. Per
Season c Max. Seasonal

Applic. Rate

( lb ai/A ) PHI d Use

Directions
and
Limita

tions e

Ground
and Aerial Equipment GF

- 2685 WG

(62719

- AAG) 0.004 5 2 0.00 91

60 Days See
Footnotes GF

- 2686 WG
(62719

- AAG) 0.0049 1 0.0049

GF

- 2687 WG (62719

- AAG) 0.0049 1 0.0049

GF

- 2688 EC (62719

- AAG) 0.0058 1 0.0058

a: Do not apply using any type of chemigation equipment
b : WG: Water dispersible granule
EC: Emulsifiable concentrate

c : The maximum number of applications per season is not specified on the label. Those given in the table are inferred based on the single application rates and the maximum seasonal application rate.
d : PHI: Do not apply within 60 days of crop harvest. Do not apply closer than 21 days before cutting of hay. Livestock may be grazed on treated crops 1 day following application.

e : To minimize spray drift, apply in a total spray volume of 3 gallons or more per acre. Do not apply halauxifen

- methyl to more than two growing seasons per year.



### 4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue (860.1300/1850)

References:

Halauxifen

- Methyl . ROCKS Briefing Memorandum for Meeting of November 14 , 201 3

, D 416123 , D. Dotson, 7 / 11 /201 4

Halauxifen

- methyl: Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS), D416125, E. Holman, 5/20 /201 4Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 12 of 56 48557789.DER.docx : Wheat Metabolism Study
48557807.DER.docx : Turnip Metabolism Study
48557791.DER.docx : Goat Metabolism Study
48557 790.DER.docx : Hen Metabolism Study
48557813.DER.docx : Confined Rotational Crop Study

Dow AgroSciences submitted studies depicting the metabolism of halauxifen

- methyl in wheat

, turnips , laying hens, lactating goats, and rotational crops. The proposed metabolic pathways for
halauxifen

- methyl are included in Attachment 6.

4.1.1 Summary of Plant Metabolism

Nature of the Residue in Wheat

In the w heat metabolism study , a single foliar application of halauxifen

- methyl formulated as an emulsifiable concentrate (EC) with and without a safener w as made to wheat at approximately the maximum proposed seasonal application rate of 0.009 lb ai/A (1x application rate)

. The application was made at the latest growth stage for bot h spring and winter wheat (BBCH 45). Forage was harvested at growth stage BBCH 49, hay was harvested at growth stage BBCH 75, and straw and grain were harvested at growth stage BBCH 89. The result ing total radioactive residue (TRR) levels in the various commodities are as follows: immature forage ( 0.09

- 0.20

ppm ), immature hay ( 0.24

- 0.41 ppm ), m ature straw ( 0.0 6

- 0.35 ppm ), and grain ( ≤ 0.004 ppm )
halauxifen

- methyl equivalents.

The majority of the residues were found to be readily extractable with a mil d procedure, and minimal additional residues were extractable with stronger procedures. Typically 6 6

- 81% of the residue was extracted from forage, hay

, and straw samples and was further characterized by h igh

p erformance l iquid c hromatography ( HPLC )

.

Th e neutral accelerated

- solvent extract (ASE) of immature forage consisted of multiple components, including low levels of parent halauxifen

- methyl (4

- 9% of the TRR), X11449757 (approx. 5% of the TRR ), XDE

- 729 acid ( X11393729

, 0.6

- 2.0 % of the TRR), X118616 62 (4

- 5% of TRR), X11406790 (3

- 4% of TRR), X11406790 glucose conjugate (2

- 3% of the TRR), and X11406790 glucose

- malonyl conjugate (X12245409, 6

- 10% of the TRR). No other single component accounted for more than 4% of the TRR or 0.01 mg eq/kg. The samples from four different plots showed similar metabolite levels, which indicates there is no significant effect of
the safener on the transformation of halauxifen

- methyl in wheat.

The HPLC profile of the neutral accelerated solvent extract of hay and straw was similar to the HPLC profile of the forage extract. The following were present at very low levels: parent halauxifen

- methyl (1

- 5% of the TRR), X11449757 (2% of the TRR), XDE

- 729 acid (1

- 2 % of the TRR), X 11861662 (0.5

- 3% of TRR), X11406790 (0.5

- 1% of TRR), X11406790 glucose conjugate (3

- 5% of the TRR), and X11406790 glucose

- malonyl conjugate (X12245409, 3

- 6% of the TRR). No other single component accounted for more than 4% of the TRR or 0.01 mg eq/kg.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 13 of 56 The pectin substances in the non

- extractable resi due were solubilized using ethylenediamine

tetraacetic acid (EDTA), 50 mM in pH 4.5 buffer. After heating, cooling, and vacuum filtration, the samples were analyzed by liquid scintillation counting. The lignin was removed from the solids remaining after the pectin solubilization with sodium chlorite and glacial acetic acid. The total amount of radioactivity in the liquid fraction, which included dissolved lignin, was determined by LSC analysis. After air

- drying overnight, the remaining solids were weigh ed and
used in the a cid

- detergent f iber (ADF) i solation procedure. The ADF fraction was isolated from the solids remaining after the lignin extraction step. The pellet from the lignin extraction step was refluxed in acid detergent solution

. Following th e reflux period, the solids were removed by
vacuum filtration . T he remaining solids (the ADF fraction) were weighed and combusted. The
ADF fraction consist ed of cellulose and include d radioactivity encapsulated by cellulose. The
total amount of radioact ivity in the liquid fraction, which include d hemicellulose and dissolved plant proteins, was determined by LSC analysis. I n forage

, the non

- extractable radioactivity was
associated with

, and distributed amongst

, natural components: pectin (0.6

- 1.8% of the TRR), lignin (4.5

- 9.4% of the TRR), ADF

- soluble fraction (6.5

- 9.1% of the TRR), and ADF ( 6.2

- 8.3%
of the TRR ) . In hay tissues, similar levels of radioactivity were incorporated into pectin (1.8

- 2.4% of the TRR), lignin (7.4

- 8.8% of the TRR), ADF

- soluble (4.7

- 9.9% of the TRR)

, and ADF (6.4

- 8.6% of the TRR). In straw tissues, the radioactivity was associate d with pectin (0

- 2.4% of the TRR), lignin (8.7

- 13.2 % of the TRR), ADF

- soluble (6.3

- 9.8 % of the TRR), and ADF (6.6

- 7. 5 % of the TRR). The results demonst rated similar levels of incorporation or encapsulation of radioactivity into pectin, ADF

- soluble, and ADF of forage, hay

, and straw tissue. There is more radioactivity associated with lignin in the straw, which is to be expected as the plant grows.

No characterization of radioactivity was performed for the grain samples because of the low TRR levels (≤ 0.004 ppm halauxifen

- methyl equivalents).

Metabolism of halauxifen

- methyl in wheat is extensive and proceeds through dissociation to produce XDE

- 729 acid or de-methylation of the methoxy group on the phenyl ring to produce the metabolite X11406790. X11406790 is then conjugated with glucose followed by further conjugation with malonic acid. Metabolism continues through natural incorporation of the

ra diolabeled carbon into natural plant constituents, such as pectin and lignin. The l ow levels of
X11861662 are likely the result of photodegradation.

Nature of the Residue in Turnips

In the turnip metabolism study

, a foliar application of halauxifen

- methyl was made at the maximum proposed seasonal application rate of 0.0089 lb ai /A (0.0086 lb ae/ A ) . The application was made at growth stage BBCH 17. M ature PH

- labeled roots and tops sampled at a PHI of 14 days contained 0.001 and 0.091 ppm halauxifen

- methyl equivalents, respectively. The PY

labeled mature roots and tops contained 0.002 and 0.109 ppm halauxifen

- methyl equivalents, respectively.

Because of the low levels of radioactivity, the roots were not analyzed further. Immature and

ma ture foliage contained consistent metabolites at similarly low levels. In the mature foliage, the
radioactive residue was identified as halauxifen

- methyl (7% of the TRR, 0.006

- 0.008 ppm ),
XDE

- 729 acid (3% of the TRR, 0.003

- 0.004 m g equiv./ k g), glucose con jugate of XDE

- 729 acidHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 14 of 56 (13

- 14% of the TRR, 0.012

- 0.015 mg equiv./ k g), a malonyl glucose conjugate of X11406790 (7% of the TRR, 0.006

- 0.008 mg equiv./ k g), two N

- glucose conjugates of halauxifen

- m ethyl (anomer 1: 15

- 17% of the TRR, 0.014

- 0.019 m g equiv./ k g, anomer 2: 9

- 10% of the TRR, 0.009

- 0.010 mg equiv./ k g), and X11406790 (2

- 3% of the TRR, 0.002 mg equiv./ k g). The levels of the radiolabeled metabolites were the same irrespective of radiolabel, indicating no evidence of bridge cleavage.

I ndividual meta bolite levels were low, with the majority of the radioactive residue being
identified as halauxifen

- methyl

, either as parent compound or, more predominantly, as N

- glucose conjugates . Additionally, de

- methylation metabolites XDE

- 729 acid and X11406790, and glucose or malonyl

- glucose conjugates of these metabolites were also observed. The high proportions of conjugates to primary metabolites indicate that conjugation is a preferential route of metabolism. The overall metabolic pathway is consistent with th e metabolic pathway
observed in wheat.

4.1.2 Summary of Confined Rotational Crops (860. 1 850)

Halauxifen

- methyl radiolabeled in either the phenyl or pyridine ring was applied to plots of bare sandy loam soil at the maximum seasonal rate of 0.009 lb ai/A (1x application rate)

. R adish, lettuce, and wheat were sown a t plant

- back intervals of 14, 90, and 270 days. The crops were grown outdoors to maturity at Ricerca, Ohio. Plot maintenance simulated typical cultural practices.

From each plant

- back interva l, immature lettuce, mature lettuce, mature radish tops, mature radish roots, wheat forage, wheat hay, wheat grain

, and wheat straw were harvested. The harvested crops were milled and combusted to determine TRR levels. All crop fractions
harvested contai ned less than 0.01 ppm halauxifen

- methyl equivalents, and were therefore not analyzed further.

In practical use, halauxifen

- m ethyl is a foliar treatment to be applied to a crop

, and not directly to the bare soil. The crop will intercept a majority of the applied halauxifen

- m ethyl, such that the soil will only receive a portion of the application. T RR in the rotated crops were below 0.01

ppm halauxifen

- m ethyl equivalents over the three plant

- back intervals. Because of the very low TRR levels, none of the residues in tissue samples were characterized further.

T able 6

. T RR in C onfined R otational C rop Tissue Matrices

Raw Agricultural Commodity plant

- back

interval PH TRR PY TRR (days) (dpm/g) ( ppm ) a (dpm/g) ( ppm ) a

radish tops 14 56 <LOQ b 64 <LOQ b

radish roots 14 90 <LOQ 83 <LOQ

immature lettuce 14 178 0.001 227 0.001

mature lettuce 14 68 <LOQ 50 <LOQ wheat forage 14 95 <LOQ 55 <LOQ wheat hay 14 197 0.001 234 0.001 wheat grain 14 194 0.001 144 <LOQHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 15 of 56 T able 6

. T RR in C onfined R otational C rop Tissue Matrices

Raw Agricultural Commodity plant

- back

interval PH TRR PY TRR (days) (dpm/g) ( ppm ) a (dpm/g) ( ppm ) a

wheat straw 14 229 0.001 193 0.001 radish tops 90 93 <LOQ 65 <LOQ

radish roots 90 55 <LOQ 77 <LOQ

immature lettuce 90 131 <LOQ 101 <LOQ

mature lettuce 90 127 <LOQ 181 0.001 wheat forage 90 137 <LOQ 91 <LOQ wheat hay 90 164 0.001 140 <LOQ wheat grain 90 104 <LOQ 85 <LOQ

wheat straw 90 141 <LOQ 131 <LOQ radish tops 270 110 <LOQ 95 <LOQ

radish roots 270 79 <LOQ 93 <LOQ

immature lettuce 270 172 0.001 113 <LOQ

mature lettuce 270 311 0.001 141 <LOQ wheat forage 270 111 <LOQ 122 < LOQ wheat hay 270 158 <LOQ 166 0.001 wheat grain 270 242 0.001 240 0.001

wheat straw 270 98 <LOQ 64 <LOQ

a mg halauxifen

- methyl equivalents/kg tissue

b Less than the limit of quantitation (LOQ), where LOQ = 0.00055 ppm for the PH

- label and LOQ = 0.00082 ppm for the PY label



### It is unlikely that crops rotated into cereal grain fields treated with halauxifen

- methyl at 0 .009 lb
ai/A would result in detect a ble levels of halauxifen

- methyl in any r aw a gricultural c ommodity. Because of the low residue levels expected, a field rotational crop study was not conducted

.

Based on results from the confined rotational crop study, which indicated a very low potential for residues in succeeding crops, no field residue trial s with succeeding crops are necessary , and no rotational crop plantback restrictions are required

.

4.1. 3 . Summary of Livestock Metabolism (860.1300)

Nature of the Residue in Ruminants

In the goat metabolism study , goats were dosed for 5 days a t a feeding level of approximately 11 ppm dry feed per day ( 35x the dairy cattle dietary burden ) . Halauxifen

- m ethyl was primarily eliminated in the feces (40.9

- 45.9% of the dose (both labels) , includ ing GI contents). Approximately 25% of the dose (20.4

- 28.9% , both labels ) was absorbed and eliminated in the urine. Less than 0.1% of the dose was recovered in the combined milk samples, and only one milk sample (PY

- labeled day 3 p

. m

. ) contained greater than 0.01 ppm halauxifen

- m ethyl equivalents. Analyses of milk showed the residue levels reached a plateau during the dosingHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 16 of 56 phase. Less than 0.2% of the dose (both labels) was recovered in the combined edible matrices.
Muscle and most fats contained less than 0.01 ppm halauxifen

- methyl equivalents.

The following metabolites were all detected in edible tissues and/or milk : the sulfate conjugate of X11449757 (or isomer), X11449757, XDE

- 729 acid , the N

- or O

- glucuronic acid conjugate of X11406790 (or isomer), the N

- glucuronic acid conjugate of halauxifen

- m ethyl (or isomer), the sulfate conjugate of X11406790 (or isomer), and X11406790. Less than 0.001 ppm halauxifen

m ethyl was detected in milk or any edible tissue. Generally, the above components totaled greater than 61% of the residues in milk and tissue s . T he remaining residue was characterized as
multi

- component. In the edible matrices, metabolite X11449757 was observed at the highest level, 0.048 ppm halauxifen

- m ethyl equival ents (62% of the TRR), in the PH

- labeled liver, followed by the XDE

- 729 acid (0.044 ppm, 36.7% of the TRR; PH

- labeled kidney)

.

Metabolism in goats proceeds through demethylation of the methyl ester (forming X DE

- 729
acid ) , the methoxyphenol ( forming X11406790), or both ( forming X11449757). Parent
halauxifen

- m ethyl and its metabolites can conjugate wi th sulfate or glucuronic acid.

Nature of the Residue in Poultry

Dow AgroSciences submitted the results of a hen metabolism study in which hens were dosed
with halauxifen

- methyl that was radiolabeled in either the phenyl (PH) ring or the pyridinyl (PY) ring. Hens dosed with the phenyl

- labeled material were dosed at a level of 11.3 ppm in the diet ( 1,500x the poultry dietary burden ) . Hens dosed with the pyridinyl

- labeled material were dosed at a level of 11.6 ppm in the diet. Halauxifen

- methyl was rapidly eliminated in the excreta (94.5 and 93.8% of the dose, from the PH

- and PY

- labeled groups, respectively). Less than 0.1% of
the dose was recovered in the combined edible matrices. Muscle and most fats contained less
than 0. 01 ppm halauxifen

- methyl equivalents. Residues in liver were readily extractable with neutral organic solvents (acetonitrile:water or methanol:water)

. X DE

- 729 acid, X11449757 , its sulfate conjugate

, X11406790, and its sulfate conjugate were all detected. No halauxifen

- methyl
was detected. Less than 0.02 ppm halauxifen

- methyl equivalents were either unextractable or characterized as being multi

- component.

In hens, m etabolism proceeds through demethylation of the methyl ester (forming X DE

- 729
acid ) , the methoxyphenol ( forming X11406790), or both ( forming X11449757). The metabolites

c a n conjugate with sulfate. I n the edible matrices that were analyzed, metabolite X11449757 was typically observed at the highest level.

4.1. 4

. Summary of Metabolites and D egradates

T he petitioner has adequately characterized the nature of the halauxifen

- methyl residue in rotational crops and livestock commodities. In addition, for the purposes of this tolerance petition, the petitioner has adequately characterized the nat ure of the halauxifen

- methyl residue
in plants.

There are no outstanding data deficiencies associated with the nature of the residue guideline requirements. The petitioner submitted adequate plant metabolism and field trial data forHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 17 of 56 determination of the residues of concern in cereal grain commodities for tolerance enforcement. In addition, the petitioner submitted adequate livestock metabolism data and feeding study data
for determination of the residues of concern in livestock commodities for tolerance enforcement.

A summary table of the major and minor metabolites found in the nature of the residue studies, the confined rotational crop study, and the environmental degradation studies can be found in Attachment 5. The proposed metabolic pathways of hal auxifen

- methyl in wheat, turnips, goats, hens, and rats can be found in Attachment 6. This attachment also contains the proposed
environmental transformation scheme for halauxifen

- methyl.

4.2 Comparison of Metabolic Pathways

Parent halauxifen

- methyl un dergoes the same demethylation in wheat, turnips, goats, hens, and rats. In addition, many of the primary metabolites seen in the metabolism studies are also seen in the environmental degradation studies. Halauxifen

- methyl contains two methoxy groups (i. e.,

- OCH 3 

### groups). One of these methoxy groups forms the methyl ester moiety on the chemical and the other methoxy group is attached to the phenyl ring. The primary metabolic pathways
involve conversion of either one or both of these two methoxy groups to hydroxyl groups. When the methoxy group that forms the methyl ester i s converted to a hydroxy group, the moiety becomes an acid. This compound is the XDE

- 729 acid metabolite. When the methoxy group on the phenyl ring i s converted to a hydroxyl group, the compound becomes a phenol (the
X11406 790 metabolite). Both of these metabolites can then be converted to the metabolite with both the acid and phenol moieties (the X11449757 metabolite). In plants and animals, these metabolites can conjugate with va rious moieties , depending on the plant or animal species

.

Rat metabolism studies were performed with both the parent compound as well as the XDE

- 729 acid metabolite. Rats metabolized the compounds in a comparable manner. Absorption and
excretion were ex tensive and rapid. XDE

- 729 acid was the primary metabolite of the parent compound. When rats were dosed with XDE

- 729 acid, the limited metabolism that did occur was due to acyl

- glucuronidation or O

- demethylation to form X11449757, followed by glucuronide or sulfate conjugation

. Supplemental metabolism studies were done with dogs and mice. Metabolism was extensive and rapid in these species as well

. Rats formed the same demethylated metabolites that were seen in the plant metabolism studies and in the

e nvironmental degradation studies: XDE

- 729 acid and X11449757.

4.3 Residues of Concern Summary and Rationale

The HED risk assessment team presented the metabolism data to HED’s Residues of Concern Knowledgebase Subcommittee (ROCKS). The committee recommended that the residue of concern in primary crops for both tolerance enforcement and risk assessment be parent halauxifen

- methyl only. The committee recommend ed that the residue of concern in ruminants and poultry for both tolerance enforcement and risk assessment be the metabolite X11449757.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 18 of 56 Table 7

. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance

Expression

Matrix Residues I ncluded in Risk Assessment Residues I ncluded in Tolerance Expression for Compliance Monitoring

Plants Primary Crop H alauxifen

- methyl H alauxifen

- methyl

Rotational Crop Not Applicable Not Applicable

Livestock Ruminant X11449757 X11449757

Poultry X11449757 X11449757
Drinking Water Halauxifen

- methyl + XDE

- 729 Acid + X11449757 + X11406790 + Degradates 1, 2, 4, 10, 11, and 14 Not Applicable



### The ROCKS gave the following rationale for its residues of concern recommendations for plant commodities, livestock commodities, and drinking water ( Halauxifen

- methyl: Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS), D416125, E. Holman,
5 / 20 /2 01 4 ).

Water: The ROCKS recommends including parent halauxifen

- methyl, as well as transformation products XDE

- 729 acid, X11449757, X11406790, degradates 1, 2, 4, 10, 11, and 14. Although
halauxifen

- methyl and its transformation products ( e.g. , XDE

- 729 ac id) are likely to result in different modes of toxicity; parent halauxifen

- methyl is rapidly metabolized into XDE

- 729 acid, especially at low, environmentally relevant concentrations. Therefore

, systemic exposure is essentially to XDE

- 729 acid regardless of environmental exposure to either halauxifen

- methyl or
the XDE

- 729 acid. Therefore, grouping parent halauxifen

- methyl with XDE 729

- acid for drinking water is appropriate. In the absence of toxicity data for the remaining degradates discussed below, ROC KS assumes similar toxicity to the parent unless information from other sources (e.g., SAR/QSAR or read

- across) is available.

 The chemicals structures of 1, 2, and 4 are unknown. However, analytical results indicate these degradates are more polar compa red to halauxifen

- methyl. Compounds with increasing polarity are less likely to be systemically absorbed; and that which is absorbed is more readily conjugated or excreted. Therefore, polar degradates are unlikely to be more toxic compared to halauxifen

- methyl. However, in the absence of discrete structural information or toxicity data, these residues cannot be ruled out as being residues of

concern.

 The chemical structures of degradates 11 and 14 are significantly different from the parent molecule ( i. e. , loss of picolinic acid moiety). SAR analysis using DEREK Nexus v. 1.5 is ambiguous in terms of toxicity: both halauxifen

- methyl and XDE

- 729

- acid did not produce any alerts and degradates 11 and 14 produced only skin sensitization alerts based on the

p resence of an imine groups. However, DEREK estimates of polarity indicates degradates 11 and 14 are significantly more polar (Log P of 1.86 and 1.03, respectively) compared to
the either h alauxifen

- methyl (Log P = 3.07) or XDE

- 729

- acid (Log P=3.52). Base d on the discussion of polarity for degradates 1, 2, and 4, there is no expectation of increased toxicity compared to the parent molecule nor is there any expectation of a different mode of toxicity
of concern based on minimal DEREK alerts.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 19 of 56 From an exposure perspective, degradates 1, 2, 4, 10, 11, and 14 were only observed in the aqueous photolysis study. Since aquatic photolysis is only likely to occur in clear shallow surface water and on foliar surfaces, exposure to these transformation products is expected to be primarily in surface water compared to groundwater.

Plants (Primary Crops): For dietary risk assessment and tolerance enforcement, the parent compound should be the only residue included as a residue of concern. Halauxifen

- methyl was the only quantifiable residue observed in the crop field trials, specifically in wheat straw and forage, with no quantifiable residues of halauxifen

- methyl in wheat grain or any barley matrix.
XDE

- 729 acid was not quantifiable in any of the crop field tr ials.

Rotational Crops: In the confined rotational crop study, the TRR in all commodities at all plantback intervals was 0.001 ppm or less. Because of the very low TRR levels, none of the RAC samples were characterized further. Therefore, the residue s of concern in rotational crops are not applicable at this time, nor do rotational crop tolerances need to be set at this time.

Livestock: For dietary risk assessment and tolerance enforcement, metabolite X11449757 should be the only residue of concern . X11449757 was the only quantifiable residue in the cattle feeding study, and was a major residue in the goat and poultry metabolism studies. Although quantifiable, the residues of XDE

- 729 acid, X11406790, and X11406790 conjugates were generally low (<0.01 ppm). Given the anticipated livestock dietary burden associated with the proposed uses, X11449757 is c onsidered to be adequate for enforcement and risk assessment

purposes.

. Should the dietary burden increase in the future due to proposed new uses, this decision may need to be revisited and additional data may be required, including a poultry feeding study. If poultry feeding studies are conducted in the future, then is recommended that metabolites observed in the poultry metabolism study be a nalyzed, including XDE

- 729 acid, X11406790, and X11449757.

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

References:

48557792.DER.docx, 48557793.DER.docx, 48557794.DER.docx, 48557795.DER.docx, 48557796.DER.docx, 48557798.DER.docx, 48557865.DER.docx, 48901101.DER.docx

5.1.1 Data Collection Methods

Data Collection Method for Plant Commodities

The data collection method used in the wheat and barley field trials was a n LC

- MS/MS method described in Dow Report Number 110005

. With thi s method, r esidues a re extracted from a
5.0

- gram sample by homogenizing and shaking th e sample in 100.0 mL of an acetonitrile:water ( 80:20 , v/v ) solution. One

- hundred microliters of a glycerin:methanol solution (10:90 w/v) containing a mixed ( halauxifen

- m ethyl M+4 and XDE

- 729 acid M+4 ) stable

- isotope internalHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 20 of 56 standard were added to a 500

- μL aliquot of the acetonitrile:water extraction solution

, and the sample was concentrated to near dryness. The sample extract was then diluted to 1.0 mL with a
methanol:w ater (20:80 v/v ) solution for analysis. After preparation, the solution was purified using a reversed

- phase online solid

- phase extraction procedure and analyzed by liquid chromatography using a C8 column coupled with positive

- ion electrospray tandem mass spectrometry (LC

- MS/MS), monitoring two MS/MS transitions characteristic of each analyte
and one MS/MS transition characteristic of each internal standard. Ion transitions for
halauxifen

- methyl are 345/250 (quantitation) and 345/235 (confirmation). Ion transitions for
XDE

- 729 acid are 331/250 (quantitation) and 331/235 (confirmation). The ion transition for
halauxifen

- methyl M+4 (X11901295) is 349/254 (quantitation) and the ion transition for XDE

729 acid M+4 is 335/254 (quantitation).

The method is applicable for the quantitative determination of residues of halauxifen

- methyl and
XDE

- 729 acid in agricultural commodities representative of the four OECD crop types : wet crops (turnip root and wheat for a ge), dry crops (the grain, hay, and straw of barl ey and wheat), oily crops (canola seed and soybean seed), and acidic crops (apples and oranges). The following wheat processed commodities were also analyzed: aspirated grain fractions, total bran, whole grain bread, flour, germ, gluten, shorts, and star ch. The method was successfully validated f or linearity, precision, accuracy

, and LOQ

, f o r both halauxifen

- methyl and XDE

- 729 acid.

To determine the extraction efficiency of the analytical method, samples of wheat containing
in curred residues from a meta bolism study were analyzed with the sample analysis procedure described in this summary. The results obtained using this analytical method were similar to
those from the metabolism study, demonstrating the suitability of this analytical method for the
det ermination of halauxifen

- methyl and XDE

- 729 acid in agricultural commodities.

Conclusions

The analytical procedure for Method 110005 has been successfully validated in commodities representative of the four OECD crop type s and wheat processed commodities for linearity, precision, accuracy

, and LOQ

, f o r both halauxifen

- methyl and XDE

- 729 acid.

Data Collection Method for Livestock Commodities

As part of the cattle feeding study, r esidues of halauxifen

- methyl , XDE

- 729 acid

, and X11449757 were determined using the analytical method described in Dow Report 110505

. Residues were extracted from a 1.0

- gram portion of muscle, liver, or kidney by homogeni z ing the sample in 20.0 mL of an acetonitrile/water (80:20 , v/v ) solution. R esidues were extracted
from a 1.0

- gram portion of milk

, fat , cream, or skim milk by homogeni z ing with 20.0 mL of an acetonitrile/water (80:20 , v/v ) solution plus 20.0 mL of n

- hexane. The sample was shaken and centrifuged

, and a 500

- μL aliquot of the aceto nitrile/water layer was mixed with 100 μL of a 50 ng/mL stable isotope internal standard and 1400 μL of water. After mixing and filtration, residues were analyz ed by LC

- MS/MS. The LOQ for halauxifen

- methyl , XDE

- 729 acid

, and
X11449757 in all matrices w as 0.0 1 ppm (expressed as halauxifen

- methyl equivalents)

. The LOD for these three compounds in all matrices was 0.003 ppm ( expressed as halauxifen

- methyl equivalents).Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 21 of 56 Th e method wa s validated for the determination of halauxifen

- methyl , XDE

- 729 acid

, and X11449757 in whole milk, skim milk, cream, muscle, liver, kidney, subcutaneous fat, mesenteric
fat

, and perirenal fat as part of this study. Method validation was carried out in each matrix by the analysis of five control samples fortified at the LOQ (0.01 ppm ) and five control samples fortified at 10x LOQ (0.1 ppm ). Validation recovery data, based on the quantitation ion, showed
that overall recovery averages for the analytes in all matrices ranged from 89% to 106%.

5.1.2 Multiresidue Methods (8 60.1360)

FDA Multi

- Residue Method for Plant Commodities

The FDA’s Pesticide Analytical Manual’s multiresidue methods were evaluated for their suitability for the analysis of halauxifen

- methyl and its metabolite XDE

- 729 acid

.

This study was conducted to provide supporting data for modular multiresi due method (MRM) testing for monitoring residues of halauxifen

- methyl and XDE

- 729 acid by selected methods described by protocols in Appendix II of the U

. S

. Food and Drug Administration (FDA) Pesticide Analytica l Manual (PAM) , Volume I, third edition. Protocol A was not suitable because of poor sensitivity, and Protocol C was not suitable because of degradation in the gas chromatography detector. Without an appropriate determinative step from Protocols A and C, the remaining testing by Protocols B, D, E, and F was suspended, as per the PAM protocol.

T he FDA multiresidue test procedures are not suitable for the regulatory analysis of halauxifen

methyl and XDE

- 729 acid

. There are no outstanding data deficiencies associated with the multiresidue analytical method.

QuEChERS M ultiresidue M ethod for Plant Commodities

Th e QuEChERS multiresidue method was evaluated for the quantitative determination of
residues of halauxifen

- methyl and XDE

- 729 acid in agricultural commodities representative of
the four OECD crop types: wet crop, dry crop, oily crop, and acidic crop . Residues of
halauxifen

- methyl and XDE

- 729 acid were extracted from the sample matrices by shaking with
an acetonitrile/water solution. After addition of a salt mixture consisting of magnesium sulfate, sodium chloride, trisodium citrate dihydrate, and disodium hydrogen citrate sesquihydrate, the extract was shaken. Minor modifications to the procedure were made for acidic sampl es (e.g., lemons) to make the pH less acidic. After centrifugation, an aliquot of the acetonitrile extract was purified by freezing out and/or dispersive solid phase extraction using a primary secondary amine sorbent. Subsequently, the purified aliquot w as diluted to volume with aqueous 0.1% formic acid. After preparation, the samples were analyzed by liquid chromatography using a Synergi Hydro

- RP C 18 

### column coupled with positive

- ion electrospray LC

- MS/MS, monitoring
two MS/MS transitions characteristic of each analyte. Ion transitions for halauxifen

- methyl are 345/250 (quantitation) and 345/207 (confirmation). Ion transitions for XDE

- 729 acid are 331/250 (quantitation) and 331/207 (confirmation). The method was validated over the concentration range o f 0.01

- 0.10 mg/kg with a validated LOQ of 0.01 mg/kg. Recoveries were acceptable. The method is adequate for determination of residues of halauxifen

- methyl and
XDE

- 729 acid in the four types of crops tested.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 22 of 56 5.1.3 Tolerance Enforcement Methods (860.1360 )

Analytical Enforcement Method for Plant Commodities

Dow AgroSciences proposed the analytical method described in Report Number 110004 as the tolerance enforcement method for plant commodities. Residues of halauxifen

- methyl and XDE

729 acid were extra cted from a 5.0 gram sample by homogenizing and shaking the sample in 100.0 mL of an acetonitrile:water (80:20 , v/v ) solution. Fifty microliters of a glycerin:methanol solution (10:90

, w/v) were added to a 1000 μL aliquot of the acetonitrile:water extraction
solution

, and the sample was concentrated to near dryness. The sample extract was then diluted to 1.0 mL with aqueous 0.1% formic acid and purified using a reversed

- phase polymeric solid

phase extraction (SPE) cartridge. After elution from th e SPE cartridge with a methanol:water (95:5 v/v ) solution containing 0.10% formic acid (v/v) , 200 μL of a mixed stable

- isotope internal standard solution was added to the eluate, which was subsequently concentrated to approximately 1 mL. The solution was then adjusted to 2.0 mL with water. After preparation, the samples were analyzed by liquid chromatography using a C8 column coupled with positive

ion electrospray LC

- MS/MS, monitoring two MS/MS transitions characteristic of each analyte
and one MS/MS tran sition characteristic of each internal standard. Ion transitions for
halauxifen

- methyl are 345/250 (quantitation) and 345/235 (confirmation). Ion transitions for
XDE

- 729 acid are 331/250 (quantitation) and 331/235 (confirmation). The ion transition for
halauxifen

- methyl M+6 (X11901295) is 351/256 (quantitation) and the ion transition for XDE

729 acid M+6 is 337/256 (quantitation).

The extraction efficiency of the analytical method was addressed in the plant data

- gathering method (see 48557898 .DER.docx ). The extraction efficiency in the analytical method was compared to the extraction efficiency in the nature of the residue study. The extraction efficiency was demonstrated to be suitable for the determination of halauxifen

- methyl and XDE

729 acid in agr icultural commodities.

Enforcement Method Independent Laboratory Validation

The petitioner submitted an ILV for the plant analytical method ( described in Dow Report Number 110004)

. The method was used, without alteration, by the independent laboratory
P yxant Labs, Inc., to analyze samples of wet, oily, and processed matrices fortified with
halauxifen

- methyl or XDE

- 729 acid. The method was adequately validated in a single trial in wheat forage (a wet crop), wheat flour (a processed commodity), and canola oil (an oily matrix). Fortification recoveries were within the generally recognized acceptable range.

Analytical Enforcement Method for Livestock Commodities

Dow AgroSciences proposed the m ethod described in Report 110505 as the analytical
enforcement method for halauxifen

- methyl and XDE

- 729 acid in livestock matrices. However,
HED has determined that the residue of concern in livestock commodities is X11449757. In the cattle feeding study, samples of cattle commodities were analyzed for X11449757 using a modification of the proposed enforcement method. In the event that tolerances are needed for livestock commodities in the future, the petitioner will need to submit an adequate enforcementHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 23 of 56 method for X11449757 and an IL V for the method.

Conclusions

HED has determined that the m ethod described in Dow Report Number 110004 is acceptable as an analytical enforcement method , as defined in SOP No. ACB

- 019 (9/15/2008). The m ethod is applicable for the quantitative determination of residues of halauxifen

- methyl and XDE

- 729 acid in agricultural commodities representative of the four OECD crop type s. These groupings are as follows: wet crops (turnip root and wheat forge), dry crops (barley grain, barley hay, barley straw, wheat grain, wheat hay and wheat straw), oily crops (canola seed and soybean seed), and acidic crops (apples and oranges). The method is also applicable for the quantitative
determination of residues in wheat processed commodities. Two ion transitions are available for parent

. The method was validated for each analyte at 0.01 and 1.0 ppm in all tested matrices. The LOQ for both analytes in all commodities tested is reported as 0.01 ppm.

T he FDA multiresidu e test procedures are not suitable for the regulatory analysis of halauxifen

methyl and XDE

- 729 acid

. Th e QuEChERS multiresidue method is suitable for determination of
residues of halauxifen

- methyl and XDE

- 729 acid in agricultural commodities representative of
the four OECD crop types: wet crop, dry crop, oily crop, and acidic crop

.

In the event that tolerances are needed for livestock commodities in the future, the petitioner will need to submit an adequa te enforcement method for X11449757 and an ILV for the method.

5.1.4 Submittal of Analytical Reference Standards

An analytical reference standard for halauxifen

- methyl has not been submitted to EPA’s National Pesticide Standard Repository ( NPSR ) of the Analytical Chemistry Branch (ACB) of the Biological and Economic Analysis Division (BEAD)

. The reference standard should be sent to ACB, which is located at Fort Meade, MD. It should be sent to the attention of Theresa Cole at the address listed below, along with a letter of transmittal. Please note that the full 9

- digit Zip Code is mandatory, or the mail will be returned to the registrant.

USEPA National Pesticide Standards Repository Analytical Chemistry Branch/BEAD/OPP 701 Mapes Road
For t George G. Meade, MD 20755

- 5350

The letter of transmittal should include the assay of the standard, name of the analytical method used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for safe handling. When standards expire, the registrant is required to submit a reasonable amount of new analytical reference standard or an updated certificate of analysis (COA) for the existing standard

. Material Safety Data Sheets (MSDSs)

must accompany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA) in 29CFR§1910.1200.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 24 of 56 5.1.5 Storage Stability (860.1380)

References:

49065802.DER.docx: Storage Stability in Plant Commodities
49065803.DER.docx: Storage Stability in Livestock Commodities Stability of Residues in Plant Commodities

Dow AgroSciences submitted the results of a 16

- month interim storage stability study with
halauxifen

- methyl and its metabolite, XDE

- 729 acid, in wheat grain, lettuce, rapeseed

, and whole oranges to determine the stability of the residues while stored frozen for approximately 16
months. The crops selected for frozen storage stability of residues represent the four OECD crop types : dry, high wa ter content, high fat content, and high acid content. Untreated samples of each commodity were homogenized and spiked with a mixed spiking solution containing
halauxifen

- methyl and XDE

- 729 acid , each at 0.10 ppm. Samples were placed in frozen storage at approximately

- 18 oC and analyzed at storage intervals of 0, 97 (halauxifen

- methyl only)

, 120

, 1 74

, 366 , and 489 days

.

The final extracts were analyzed for residues of halauxifen

- methyl and XDE

- 729 ac id by liquid chromatography with triple quadrupole mass spectrometric detection (LC

- MS/MS). The analytical method used was described in Dow AgroSciences Report 110005 (see
48557898 .DER.docx ). The method is applicable for the quantitative determination of residues
of halauxifen

- methyl and XDE

- 729 acid in agricultural commodities. For each compound the
method was adequately validated over a concentration range of 0.010

- 1.0 ppm with a validated LOQ of 0.010 ppm

.

The results of the study indicate that resid ues of halauxifen

- methyl and X DE

- 729 acid are stable
in a variety of crop matrices when stored fr ozen at ≤

- 18°C over the course of 489 days (16 months). Acceptable methods for quantitati o n of residues in appropriate commodities were used in the study.

Stability of Residues in Livestock Commodities

Dow AgroSciences, LLC submitted the results of an interim storage stability study with
halauxifen

- methyl and its metabolites XDE

- 729 acid and X11449757 in frozen storage.
Residues of halauxifen

- methyl, XDE

- 7 29 acid, and X11449757 were measured in bovine muscle, bovine milk, poultry liver, and poultry eggs spiked with each analyte to determine the stability of the residues while in frozen storage. This second interim report presents the results
for intervals of 0, 1, 3, 6, and 12 months (± 1 month) of frozen storage for halauxifen

- methyl and
XDE

- 729 acid

, and 0, 1, 3, and 6 months (± 2 weeks) of frozen storage for the X11449757 metabolite. The livestock samples were spiked at 0.1 ppm and were stored fr ozen at ≤

- 18°C.

Residues of halauxifen

- methyl, XDE

- 729 acid, and X11449757 were determined separately, using the same extraction method and instrumental analysis modified to use different internal
standards for X11449757. The final extracts were analyzed for re sidues of the three compounds by liquid chromatography with triple quadrupole mass spectrometric detection (LC / MS/MS).Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 25 of 56 The LOQ was confirmed to be 0.01 ppm for the three compounds in all the livestock matrices tested (bovine muscle, milk, poultry liver, a nd eggs).

The methods were validated to confirm their suitability for use in these sample matrices. Five freshly fortified samples at 0.01 ppm and five freshly fortified samples at 0.1 ppm were prepared and analyzed to demonstrate suitable recovery. For the three compounds, the average recoveries

were within the acceptable range of 70 to 120%.

Samples were analyzed for halauxifen

- methyl and XDE

- 729 acid after a maximum of 371 days of frozen storage. Samples were analyzed for X11449757 after a maximum of 182 days of frozen storage. The results show that residues of halauxifen

- methyl and XDE

- 729 acid are stable
in all tested matrices for at least 371 days. R esidues of X11449757 are stable for at least 182 days in all tested matrices while stored under frozen conditions.

Conclusions

The plant and livestock commodity storage stability studies are adequate. Residues of
halauxifen

- methyl are considered to be stable in a variety of plant matrices when stored at

- 18°C for at least 489 days (16 months). This study supports the storage intervals used in the magnitude of the residue trials and processing studies for halauxifen

- methyl. In the field trial and processing studies, all samples of all commodities were analyzed within 1 4 months of sampling. The results of the livestock commodity storage stability study indicate that residues of
halauxifen

- methyl and XDE

- 729 acid are stable in livestock matrices over the course of 371 days
when stored frozen at ≤

- 18°C, and that residues of X11449757 are stable in livestock matrices over the course of 182 days when stored frozen at ≤

- 18°C. In the cattle feeding study, all samples of all commodities were analyzed within 9 1 days of sampling.

5. 2 Residue Data

5 .2 .1 Crop Field Trials (860.1500)

References

48557805.DER.docx, 48557806.DER.docx: Wheat Field Trial Studies 48557810.DER.docx, 48557711.DER.docx: Barley Field Trial Studies

Wheat Field Trials

F ield trial studies with halauxifen

- methyl in wheat (spring and winter varieties) were conducted
in the 2010 and 2011 growing seasons

. Fourteen trials were performed in the U.S. and thirteen were performed in Canada, for a total of twenty

- seven trials. At each t rial location, consisting of one untreated and one treated plot, halauxifen

- methyl (GF

- 2685, a 1 0% water dispersible granule ( WDG ) containing 104

- 106 g a.e. halauxifen

- methyl /kg formulated with a safener) was applied as a single foliar spray broadcast treatment at approximately the flag leaf stage (BBCH39; actual stages at application: BBCH32

- 41) . A pplication rates were 0.0087

- 0.0099 lbs halauxifen

methyl /A. Duplicate samples were collected from the treated plots

, and a single sample wasHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 26 of 56 collected from the untreated control plots. Forage samples were cut and collected, and hay samples were cut 1 da y (BBCH33

- 41; BBCH 43

- 55 at one 2011 trial site) and 17

- 31 days (BBCH65

- 85; late flowering to soft

- dough stage) after treatment (DAT), respectively . S amples of straw and grain were collected at early maturity, at PHIs of 42

- 73 days (BBCH87

- 97, with the

ex ception of samples from four of the 2010 trials for which the exact growth stage was unknown: referred to as “BBCH99”). The applications were made in volumes of 10.4

- 20.5 gallons/A (GPA) (97

- 192 L/ha) and a locally available adjuvant was included in all spray mixtures.

R esidue decline behavior was evaluated at two sites from the 2010 trials . F orage was collected and hay samples were cut at PHIs of 1, 7, 14, 21

, and 28 days, and grain and straw samples were collected approximately 7 days prior to maturity and subsequently at 7, 14, 21

, and 28 days after maturity, at PHIs ranging from 45

- 85 days. Hay samples from all trials were dried to a moisture
content of 10

- 20% in the field or under a shelter 1

- 13 days prior to collection. Grain samples

were separated from straw using a field or stationary combine

, and straw samples were collected from the material remaining after combining.

R esidues of halauxifen

- methyl were <0.0 1 ppm in all samples of wheat grain. Residues ranged
from 0.0 36 ppm to 0.3 8 9 pp m in wheat forage, <0.0 1 ppm to 0.0 2 6 ppm in wheat hay, <0.0 1 ppm to 0.0 1 3 ppm in wheat straw

.

In the two decline trials, quantifiable residues of halauxifen

- methyl were observed only in forage and hay at the earliest sampling interval of 1 day

. The maxi mum residue in forage was 0.049 ppm and that in hay was 0.304 ppm

. Residues declined to <0.01 ppm at the subsequent sampling
interval of 7 days and remained non

- quantifiable at all remaining intervals.

Barley Field Trials

B arley field trial studies were conducted in the 2010 and 2011 growing seasons. Eight trials were performed in the U.S. and ten were performed in Canada, for a total of eighteen trials. At
each t rial location, consisting of one untreated and one treated plot, h alauxifen

- methyl (GF

- 2685, a 10% WDG containing 104

- 106 g a.e. halauxifen

- methyl /kg formulated with a safener ) was applied as a single foliar spray broadcast treatment targeting the flag leaf stage (BBCH39; actual crop stages at application were BBCH22

- 49)

. A pplication rates were 0.0089

- 0.0098 lbs
halauxifen

- methyl /A (9.98

- 10.98 g halauxifen

- methyl /ha )

. Duplicate samples were collected from the treated plots

, and a single sample was collected from the untreated control plots. Hay samples were cut 17

- 33 D AT (BBCH73

- 85; between milk and soft dough stages) and samples of straw and grain were collected at early maturity, at PHIs of 43

- 83 days (BBCH85

- 92). The applications were made in volumes of 10.4

- 20.4 GPA (97

- 191 L/ha) and a locally available adjuvant wa s included in all spray mixtures. Residue decline behavior was evaluate a t two sites
from the 2010 trials . H ay samples were cut at PHIs of 1, 7, 14, 21

, and 28 days (approximately spanning the interval between application and hay cutting at milk to dough stage), and grain and straw samples were collected approximately 7 days prior to earliest maturity, and at 7, 14

- 17, 21

, and 28

- 31 days after earliest maturity, at PHIs ranging from 38

- 78 days. The majority of hay samples from all trials were dried to a moisture content of 8

- 20% in the field or under a shelter 1

- 18 days prior to collection, with the exception of two of the 2010 trials in which moisture content
was >20% in one trial because of incomplete sample drying and <8% in another trial

. Grain wasHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 27 of 56 s eparated from straw using a field or stationary combine

, and straw samples were collected from the material remaining after combining. The residues of halauxifen

- methyl were non

quantifiable in all barley hay, straw

, and grain samples

.

In the two decline trials, quantifiable residues of halauxifen

- methyl were observed only in hay at the earliest sampling interval of 1 day . The maximum residue value was 0.2 3 ppm. Residues in hay were below the LOQ of 0.01 ppm in all other samples at all other PHIs . Residues in grain and straw were <0.01 ppm in all samples taken at all PHIs.

Table 8. Summary of Residues from the NAFTA Crop Field Trials with Halauxifen

- Methyl

Proposed Use: 0.0088 lb a i /acre (9.8 g/ha) total application rate

1

- day PHI for Forage

21

- day PHI for Hay

60

- Day PHI for Grain and Straw

Crop Matrix Applic. Rate

lb ai/ A
(g ai/ha) PHI

(days) Residues (ppm)

n Min Max LAFT HAFT 1 Median M ean

. Std.
Dev. 2

Wheat

Wheat Forage

0.0087

- 0.0099

(9.7

- 11) 1 27 0.036 0.389 0.043 0.384 0.157 0.159 0.08

Wheat Hay 17

- 31 27 <0.01 0.026 <0.01 0.025 <0.01 0.011 0.004

Wheat Grain 42

- 73 27 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 NA

Wheat Straw 42

- 73 27 <0.01 0.013 <0.01 0.012 <0.01 <0.01 0.0004

Barley

Barley Hay

0.0089

- 0.0098

(9.98

- 11) 17

- 33 18 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 NA

Barley Grain 43

- 83 18 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 NA

Barley Straw 43

- 83 18 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 NA

1 : HAFT = Highest Average Field Trial.
2: Std. Dev.: Standard Deviation. B lank cell indicates that all field trial samples are below the LOQ.



### Conclusion

The field trial residue data for wheat and barley are adequate for tolerance s etting purposes . The field trials were performed at the maximum label application rate

, and samples were taken at the appropriate PHIs. The adequacy of the numbers of trials and their geographic distribution are
addressed in the Field Trial Geographic Distribution section of this document, below. The
recommended tolerances are listed in Ta ble 1 of this document.

Field Trial Geographic Distribution

The field trial geographic distribution was adequate for wheat and barley

. The t able inHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 28 of 56 Attachment 2 provides the distribution of the submitted field trials between Canada and the U.S.,
as well as the numbers of recommended field trials based on guidance in the OCSPP 860 .1500 Residue Chemistry Guidelines.

The petitioner submitted 27 field trials for wheat, whereas the Guidelines recommend that a minimum of 20 trials be performed. The recommend ed numbers of trials were performed in each of the recommended zones with the exception of Zone 8. The Guidelines recommend that
six trials be performed in Zone 8; however, only three were performed there. The petitioner performed one trial in Zone 6; ho wever, which is a southern zone adjacent to Zone 8. In addition, the petitioner performed a total of seven more trials than are recommended. Given the overall number of trials and the low residue levels, HED considers the geographic distribution of
the w heat field trials to be adequate.

The petitioner submitted 18 field trials for barley, which is the number that the Guidelines recommend. The recommended numbers of trials were performed in each of the recommended zones. As a result, HED considers the geographic distribution of the barley field trials to be adequate.

Conclusions

The numbers of field trials performed and their geographic distribution w ere adequate for both wheat and barley

.

5. 2 .2 Field Rotational Crops (860.1900)

Reference : 48557813.DER.docx

. Confined Rotational Crop Study

Based on the results of the confined rotational crop study, it was determined that i t is unlikely that crops rotated into wheat fields treated with halauxifen

- methyl at 0.009 lb ai/A would have
detect a ble levels of halauxifen

- methyl or metabolites in any r aw a gricultural c ommodity. Because of the low residue levels expected, a field rotational crop study was not conducted

. The GF

- 2685, 2686, 2687, and 2688 labels all give a rotation interval of 0 months f or wheat, barley, and triticale. The labels state that the following crops have a 3

- month rotation interval: camalina, canola, oats, field corn, popcorn, seed corn, sweet corn, millet, mustard, rye, sorghum, and grasses. A 9

- month rotation interval is l isted for alfalfa, cotton, chickpea, dry bean, peas (dry and succulent), flax, peanut, safflower, soybean, and sunflower. Other crops not listed on
the label have a 15

- month rotation interval. T he rotational crop statements on the labels are adequate.

5. 2 .3 Processed Food and Feed (860.1520)

Reference : 48557812.DER.docx

. Wheat Processing Study

A wheat field trial for halauxifen

- methyl was conducted in the United States ( York, Nebraska, NAFTA Region 5) during the 2010 growing season. The trial included three plots . O ne plot was
untreated

, one plot was treated at the 1 x proposed use rate , and one plot was treated at anHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 29 of 56 exaggerated use rate (5 x )

. The 1x and 5x plots were located side

- by

- side. The test material was
GF

- 2685, a WDG containing hala uxifen

- methyl at 100 g ae/kg formulated with a safener. For
the 5x plot, a single foliar application was made to the crop at the flag leaf stage (approximately BBCH39) at a target rate of 0.0445 lb ae /A halauxifen

- methyl (equivalent to 52.1 g

ae /ha halaux ifen

- methyl ) plus the safener

. The 1x plot was treated to determine the residues in/on wheat grain following a single foliar application at a rate of 0.0 0 89 lb ae/A halauxifen

methyl in spray volumes of 20.4 GPA (191 L/ha). A safener and a n adjuvant (LAS ER, a paraffinic mineral oil and surfactant blend) w ere included in the spray applications (0.5%, v/v). Field samples (grain) were collected 60 days after application to each plot (BBCH 89)

.

The wheat grain samples from the untreated and 5x treated plots were processed into food fractions using simulated commercial practices as closely as possible. Specifically, the processing phase was carried out to obtain samples of aspirated grain fraction s , bran, total bran, flour (dry mill), whole meal flour, flour

- 550, bread (white), whole grain bread, middlings, shorts, germ, gluten, gluten feed meal, and starch.

All samples were frozen at the testing facility within 2.5 hours of collection and remained frozen during shipping and storage, generally ≤

- 20 ° C , prior to processing and analysis. The maximum storage duration for wheat grain samples was 298 days from RAC harvest to extraction for analysis and 51 days from processing to extraction for analysis . All extracted samples were analyzed within 10 days. Storage conditions and durations are supported by studies showing that
residues of halauxifen

- methyl are stable in wheat grain, rapeseed, lettuce, and oranges for up to 489 days under frozen conditions.

Samples in the current study were analyzed using th e method described in Dow AgroSciences Report Number 110005, a n LC

- MS/MS method that determine s residues of halauxifen

- methyl
and XDE

- 729 acid. Acceptable method validation and concurrent recoveries were reported for each analyte for grain, total bran, wh ole meal flour, whole grain bread, shorts, germ, aspirated grain fraction s , and gluten , at spiking levels of 0.01 and 0.1 ppm, thus validating the method. Recoveries for the other fractions are assumed to be covered by the data on the available
fractions listed above . The LOQ in wheat grain and process ed fractions w as 0.01 ppm for each analyte. The LOD was 0.003 ppm for each analyte.

Residues of halauxifen

- methyl and XDE

- 729 acid were below the limit of detection in all unprocessed wheat grain samples from both the 1x and 5x plots a s well as in all processed commodities. As a result, processing factors were not determined for any of the processed
commodities.

Conclusions to Processing Stud y

Tolerances are not needed for wheat or barley processed commodities. In the wheat processing study, an exaggerated application rate of 5x was used. All samples of unprocessed grain and processed commodities contained residues below the limit of detection. In addition, in all wheat and barley field trials, re sidues were below the LOQ in all samples of grain. HED concludes that the processing data are adequate

, and that tolerances are not needed for processed commodities.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 30 of 56 5. 2 .4 Meat, Milk, Poultry, and Eggs (860.1480)

Reference : 48557802.DER.docx

. Cattl e Feeding Study

Both wheat and barley have livestock feed items associated with them. These livestock feed items include the following: wheat forage, wheat grain, wheat hay, wheat straw, barley hay, barley grain, and barley straw . Because there is the potential for transfer of residues to livestock commodities, Dow AgroSciences submitted the results of a cattle feeding study. Dow did not perform a hen feeding study, however, because the hen metabolism study demonstrated that
residues would not be expec ted to be present in poultry commodities.

5. 2 .4.1 Diet ary Burden

D ietary burden s for beef cattle, dairy cattle, swine, and poultry were calculated according to HED’s guidance document: “Revisions of Table 1 Feedstuffs (OCSPP Guideline 860.1000).” This document provides guidance for constructing balanced diets that take into account the nutritional needs of livestock animals. Cattle, swine, and poultry require adequate amounts of protein, carbohydrate, and roughage in their diets. The diets that have been constructed ensure
that these nutritional needs are met. The diets are consi dered to be maximum reasonably balanced diets ( MRBD s ) because for each of the three f ee d groups given (i.e., protein, carbohydrate, roughage) , the commodities with the highest recommended tolerances were used to construct the diets. As a result, the diets are high

- end, conservative estimates of the residue
levels to which the livestock animals might be exposed. The tables below provide the dietary burdens for beef cattle, dairy cattle, poultry , and swine

. In the following tables, R represents roughage, C C represents carbohydrate concentrate, and PC represents protein concentrate. The contribution of a particular feed item to the diet is determined with the following equations:
Contribution = [( residue /% DM ) x ( % in diet) ] for beef and dairy cattle; and contribution = [ ( residu e) x ( % in diet) ] for poultry and swine.

As can be seen in the following table, the dietary burden s for beef cattle, dairy cattle, swine, and poultry are 0.01 2 , 0. 3 2, 0.00 2 , and 0.00 75 ppm, respectively.

Table 9. Calculation of Dietary Burdens of Halauxifen

- Methyl Residues to Livestock.

Feedstuff Type 1 % Dry
Matter 2 % Diet 2 Indicate if
HAFT or
Median Residue Level

(ppm) Dietary

Contribution (ppm) 3

Beef Cattle (R = 15%; CC = 80%; PC = 5%)

Wheat Grain CC 89 20 Median 0.011236 0.002247
Wheat Hay R 88 15 HAFT 0.028409 0.004261
Barley Grain CC 88 50 Median 0.011364 0.005682

TOTAL BURDEN

-- -- 85

-- 0.01219
Dairy Cattle (R = 45%; CC = 45%; RC = 10%)
Wheat Forage R 25 20 HAFT 1.5360 0.30720

Wheat Grain CC 89 20 Median 0.011236 0.002247Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 31 of 56 Table 9. Calculation of Dietary Burdens of Halauxifen

- Methyl Residues to Livestock.

Feedstuff Type 1 % Dry
Matter 2 % Diet 2 Indicate if
HAFT or
Median Residue Level

(ppm) Dietary

Contribution (ppm) 3

Wheat Hay R 88 20 HAFT 0.028409 0.005682

Wheat Straw R 88 5 HAFT 0.013636 0.000682
Barley Grain CC 88 25 Median 0.011364 0.002841

TOTAL BURDEN

-- -- 90

-- 0.318652

Swine (CC = 85%; PC = 15%)
Barley Grain CC

- 20 Median 0.002 0.002

TOTAL BURDEN

-- -- 20

-- 0.002
Poultry (CC = 75%; PC = 25%)
Barley Grain CC

- 20 Median 0.0075 0.0075

TOTAL BURDEN

-- -- 20

-- 0.0075

1 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate.

2 Table 1 Feedstuffs (July 2008).

3 Contribution = ([HAFT or median/% DM] x % d iet) for beef and dairy cattle
C ontribution = ([HAFT or median] x % diet) for poultry and swine.



### 5. 2 .4.2. Estimated Secondary Residues in Livestock

Potential Residue Levels in Ruminant Tissues and Milk

Lactating Friesian/Holstein dairy cows were dosed orally for 28 or 29 consecutive days via a compound feed containin g t he test item, halauxifen

- methyl

. The test item was added to the compound feed as a solution in acetone on two occasions each day ( a.m. a nd p.m. feeding). The animals were divided into 4 separate treatment groups. One treatment group of 3 cows was an untreated control group, which was dosed by adding acetone only to the compound feed. The remaining groups were f

ed halauxifen

- methyl at th e following levels in the feed (on a dry matter (DM) basis): 1.0 ppm halauxifen

- methyl (4 cows)

, 3.1 ppm halauxifen

- methyl (4 cows)

, 15.6

ppm halauxifen

- methyl ( 1 6 cows)

.

As discussed above , the dietary burden for dairy cattle is 0. 3 2 ppm and that for beef cattle is
0.01 2 pm. T he dose rates represent 3.1 x, 9.7 x, and 49 x, respectively, the dietary burden for dairy
cattle and 83 x, 2 60 x, and 1

, 3 00 x, respectively, the dietary burden for beef cattle. The dose rates used in the dairy cattle feeding study ar e considered to be adequate because the low est dose level is sufficiently close to the dietary burden , and residues in cattle tissues were generally non

detectable at even the highest fee ding level. In the few samples that had detectable residues, the
lev els were low.

Twelve of the cows in the 15.6 ppm treatment group were used to generate depuration data (3, 5,
10

, and 15 days after the final dose)

. At the end of the dosing period, they were transferred to
the control diet to measure the decline in resi dues following withdrawal of the test item from the
diet.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 32 of 56 Residues of halauxifen

- methyl , XDE

- 729 acid

, and X11449757 in milk and tissues were measured using an LC

- MS/MS method (Dow Report Number 110505 )

. The LOQ for each of the analytes in milk, skim milk, cream, muscle, liver, kidney, subcutaneous fat, mesenteric fat

, and perirenal fat w as 0.0 1 ppm halauxifen

- methyl equivalents

. The LOD for each of the analytes in
these commodities was 0.0 03 ppm halauxifen

- methyl equivalents. and 0.01 ppm halauxif en

methyl equivalents , respectively. Overall average procedural recover ies for the three analytes ( halauxifen

- methyl , XDE

- 729 acid

, and X11449757) in all matrices (whole milk, skim milk, cream, muscle, liver, kidney, subcutaneous fat, mesenteric fat and p erirenal fat) ranged from
89% to 105%.

At all dose levels, r esidues of halauxifen

- methyl and XDE

- 729 acid were below the LOQ of 0.01 ppm in w hole milk, skim milk, cream, muscle, liver, kidney, subcutaneous fat, mesenteric fat

, and perirenal fat

. At the l ower two dose levels, r esidues of X11449757 were below the LOQ of 0.01 ppm in whole milk, skim milk, cream, muscle, subcutaneous fat, mesenteric fat , and perirenal fat . At the highest dose level (15.31 ppm )

, residues of X11449757 were below the LOQ in the se commodities, w ith the exception of a single residue of 0.012 ppm halauxifen

methyl equivalents in mesenteric fat and a single residue of 0.014 ppm halauxifen

- methyl equivalents in perirenal fat.

Residues of X11449757 above the LOQ transfer red into live r at all dose levels and into kidney at
the mid and high dose levels. Regression analysis for X11449757 in liver and kidney across dose levels demonstrated a linear relationship between the dose level and the resulting residue
concentration. No regressio n analysis w as performed for X11449757 in other matrices, or for
halauxifen

- methyl or XDE

- 729 acid in any matrices because

, in almost all cases

, residues were not detected or fell below the LOQ of the method.

Depuration data generated using the 12 cows in the 15.31 ppm dose level showed that residues of X11449757 declined rapidly in liver and kidney following withdrawal of the test items from the cows’ diet. All residues were below the LOQ by 3 days of depurat ion (Day 31 of the study) . A t that time, all other residue values were ND (<0.003 ppm ) by 3 days of depuration

, except for liver from one cow with a detectable residue that was <LOQ (residue of 0.004 ppm halauxifen

methyl equivalents ).

Table 1 0 . Mean R e sidues in W hole M ilk from C ows During Dosing for at

Least 28 days with H 

### alauxifen

- M ethyl (ppm)

Feeding Level s (ppm) Halauxifen

- methyl XDE

- 729 Acid X11449757

1.0

3.1

1 5 .6 <0.01

<0.01

<0.01 <0.01

<0.01

<0.01 <0.01

<0.01

<0.01Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 33 of 56 Table 1 1 . Mean Residues in Cow Tissues Following 28 Days of Feeding with Halauxifen

- Methyl

Matrix Feeding Level

ppm Halauxifen

- Methyl XDE

- 729 Acid X11449757

Muscle 1.0

3.1

15.6 ND

ND

ND ND

ND

ND ND

ND

ND

Liver 1.0

3.1

15.6 ND

ND

ND ND

ND

ND 0.010

0.036

0.174
Kidney 1.0

3.1

15.6 ND

ND

ND <0.01

ND

<0.01 0.004

0.020

0.053

Subcutaneous Fat 1.0

3.1

15.6 ND

ND

ND ND

ND

ND ND

ND

<0.01

Mesenteric Fat 1.0

3.1

15.6 ND

ND

ND ND

ND

ND ND

ND

<0.01

Perirenal Fat 1.0

3.1

15.6 ND

ND

ND ND

ND

ND ND

ND

<0.01

ND: below the LOD of 0.003 ppm



### The storage stability of residues of halauxifen

- methyl, XDE

- 729 acid, and X11449757 in
livestock commodities has been demonstrated for sufficient duration to support this feeding study . See storage stability section of this summary document.

The results of the cattle feeding study and the dietary burden s calculated above were used to
determine whether or not tolerance s are needed for livestock commodities. As stated above, the feeding levels in the cattle feeding study turned out to be approx imately 3.1 x, 9.7 x, and 49 x the dietary burden for dairy cattle and 83 x, 2 6 0x, and 1, 3 00x the dietary burden for beef cattle.

As stated in the Nature of the Residue section of this summary document, the residue of concern
in livestock commodities for tole rance enforcement and risk assessment is the metabolite
X11449757

.

In order to use the cattle feeding study data to determine the recommended tolerance levels, the potential residue level in a particular livestock commodity wa s divided by the highest feeding level used in the feeding study, 15 .6 ppm

, to arrive at the tissue

- to

- feed ratio. The residue values at the highest dosing level were used instead of the values at the mid

- dose level because at the
mid

- dose level, most tissu es and milk had residue levels that were not quantifiable. The tissue

to

- feed ratios were then multiplied by the dietary burden to arrive at the maximum potential
residue level that might reasonably be expected to be found in milk and tissues (see Table 1 2 )

.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 34 of 56 As an example, i n the cattle feeding study

, the highest X11449757 residue in liver was 0.174

ppm (in parent equivalents )

. This value was divided by the feeding level, 15.6 ppm. The resulting value

, 0. 0 111 5 ppm , is the tissue

- to

- feed ratio

. When thi s value was multiplied by the dietary burden of 0. 32 ppm , the maximum residue expected was found to be 0. 0 0 36 ppm.

Table 1 2

. Maximum Potential Residues Expected in Ruminant Commodities

Commodity Feeding

Level ( ppm ) X11449757 Residue

in Tissue ( ppm ) * Tissue

- to

- Feed

Ratio Dietary Burden,

ppm Expected

Residue

Milk 15.6 <0.01 < 0.000 64 0.318652 <0.000 20

Muscle (cattle) 15.6 ND (<0.003) < 0.000 19 0.318652 <0.0000 6

Liver (cattle) 15.6 0.174 0.0 11154 0.318652 0.00 355
Kidney (cattle) 15.6 0.053 0.000882 0.318652 0.000 28

Fat (subcutaneous) 15.6 <0.01 0.003397 0.318652 0.001 08

Fat (mesenteric) 15.6 <0.01 <0.00064 0.318652 <0.0002 0
Fat (perirenal) 15.6 <0.01 <0.00064 0.318652 <0.0002 0 * X11449757 residue level is given in terms of ppm halauxifen

- methyl equivalents



### HED generally concludes that tolerances are not needed for a livestock commodity when the LOQ of the analytical method is greater than or equal to 5x the expected residue. As the LOQ of the method is 0.01 ppm, the expected residues need to be 0.002 ppm or less. In this case, the only commodity for which the expected residue exceeds 0.002 ppm is cattle liver. As liver is the only commodity that exceeds the 0.002 ppm value, and it only exceeds it by a small amount,
HED concludes that tolerances will not be needed for any ruminant commodities. There is no reasonable expectation of finite residues in ruminant tissues and milk (40CFR §180.6(a)(3)). Although calculations are not shown for swine commodities, t olerances are not needed for them
either. As a res ult of the low dietary burden , 0.0020 ppm, and the low transfer of residues to livestock tissues, t here is no reasonable expectation of finite residues in swine tissues.

Potential Residue Levels in Poultry Tissues and Eggs

The maximum potential residues in poultry commodities were estimated based on the results of the hen metabolism study. In that study, laying hens were dosed to a level of approximately 11.5 ppm in the diet. That feeding level is approximately 1,500x the dietary burden for poultry. I n the hen metabolism study, the tissue containing the highest residue of X11449757 was liver. The combined residue of X11449757 and the sulfate conjugate of X11449757 was <0.016 ppm in the PY label study and 0.010 ppm in the PH label study. Taking into a ccount that these studies were done at a 1,500x dose rate, the expected residues in liver would be 0.00001 ppm or less. The residue level in other tissues and eggs would be expect ed to be below this level. As a result, there is no reasonable expectation of finite residues in poultry tissues or eggs

.

Conclusions

The cattle feeding stud y is adequate and can be used to determine the need for tolerance s for
ruminant commodities. No data deficiencies are associated with the cattle feeding stud y

. BasedHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 35 of 56 on the dietary burdens that were constructed and the results of the cattle feeding stud y and the hen metabolism study , tolerances are not needed for l ivestock commodities

. There is no reasonable expectation of finite residues in livestock commodities (40C FR §180.6(a)(3).

5. 2 .5 Food Handling (860.1460)

Halauxifen

- methyl is not being proposed for use in food or feed handling establishments. As a result, this guideline topic is not relevant to this tolerance petition.

5. 2 .6 Water, Fish, and Irrigated C rops (860.1400)

T here are no proposed commodities for which this guideline topic is relevant.

6.0 Tolerance Derivation

The OECD MRL calculat ion procedures w ere used to determine the tolerance s for all
commodities. The c alculator generates MRLs based on mean field trial values. As a result, the means of the two samples taken at each trial site were input into the calculator to arrive at the
recommended tolerance s. The individual spreadsheets for the various commodities can be fou nd
in Attachment 3.

7.0 ChemSAC Reference

This memorandum was reviewed by the Chemistry Science Advisory Council (ChemSAC) on 12/11/2013 and has been revised to reflect the recommendations of that group.

List of Attachments

Attachment 1. Summary of Submitted Residue Chemistry Studies Attachment 2. NAFTA Field Trial Geographic Representation
Attachment 3 . Field Trial Data and OECD MRL Calculator Output s Attachment 4

. International Residue Limits Table
Attachment 5 . Summary Table of Important Metabolites and Degradates Attachment 6. Metabolic Pathways and Environmental Transformation Scheme
Attachment 7

. Chemical Structures of Important MetabolitesHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 36 of 56 Attachment 1: Summary of Halauxifen

- Methyl Residue Chemistry Studies

Summary of Submitted Residue Chemistry Studies

OCSPP 860
Series
Guideline MRID

Number Monograph

Annex B
Reference Title

Monograph Annex B.5: Analytical Methods

– USEPA Primary

860.1340 48557792 B.5.2.1 OECD Annex IIA 4.3/03

. Ma, M., (2012) Method Validation Study for the Determination of Residues of XDE 729 Methyl Ester and XDE 729 Acid in Agricultural Commodities and Wheat Processed Products using Offline Solid

- Phase Extraction and Liquid Chromatography with Tandem Mass Spectrometry Detection. Amended Report, Dow AgroSci ences LLC Study Number 110004. PMRA No. 2226433

860.1340 48557794 B.5.2.2 OECD Annex IIA 4.3/04

. Robaugh, D. A. (2012) Independent Laboratory Validation
of Method for the Determination of Residues of XDE

- 729 Methyl Ester and XDE

- 729 Acid in Agricultural Commodities and Wheat Processed Products using Offline Solid

Phase Extraction and Liquid Chromatography with Tandem Mass Spectrometry Detection. Dow AgroSciences LLC Study Number 110825, Pyxant Labs Study Number
2386. PMRA No. 2226435

860.1340 48557798 B.5.2.3 OECD Annex IIA 4.3/05

. Olberding, E. L. (2011) Determination of Residues of
XDE

- 729 Methyl Ester and XDE

- 729 Acid in Agricultural Commodities and Wheat Processed Products using Online Solid

- Phase Extraction and Liquid Chromatography
with Tandem Ma ss Spectrometry. Dow AgroSciences LLC Study Number 110005

. PMRA No. 2226432

860.1340 48557795 B.5.2.4 OECD Annex IIA 4.3/08

. Ma, M.; Li, Q. (2012) Method Validation Study for the
Determination of Residues of XDE

- 729 Methyl Ester and XDE

- 729 Acid in Bovi ne and Poultry Tissues using Offline Solid

- Phase Extraction and Liquid Chromatography with Mass Spectrometry Detection. Dow AgroSciences LLC Study Number 110505.
PMRA No. 2226442

860.1340 48557865 B.5.2.5 OECD Annex IIA 4.3/09

. Langridge, G. (2012). I ndependent Laboratory Validation of an Analytical Method for the Determination of XDE

- 729 Methyl Ester and XDE

- 729 Acid in Animal Matrices. Dow AgroSciences LLC Study Number 110828 CEMAS Study Number CEMS

- 5325. P MRA No. 2226441

860.1360 48557796 B.5.2.6 OECD Annex IIA 4.9/01

. Robaugh, D. A. (2011) PAM I Multiresidue Protocol Testing
for XDE

- 729. Dow AgroSciences LLC Study Number 110650 Pyxant Labs Study
Number 2339

, PMRA No. 2226443

860.1340 48557793 B.5.2.7 OECD Annex IIA 4.3/01

. Daneva, E. and Taeufer, A. (2011), Validation of a Multi

Residue Method for Determination of a XDE

- 729 Methyl Ester and XDE

- 729 Acid on Different Matrices of Plant Origin, Dow AgroSciences LLC Study Number 110293 Eurofins Analytical Services Study Number S11

- 02423. PMRA No. 2226434

860.1340 48901101 B.5.2.8 OECD Annex IIA 4.3/02

. Bacher, R. (2011), XDE

- 729: Independent Laboratory
Validation of a Multi

- Residue Method for the Determination of XDE

- 729 Methyl Ester
and XDE

- 729 Acid in Plant Matrices, PTRL Europe ID P 2399 G, Dow AgroSciences Study No. 110712, Unpublished study prepared by Dow AgroSciences LLC, 69 pgs.
PMRA No. 2226436
Monograph Annex B.7.0, B.7.1, B.7.2, B.7.8, B.7.9: Storage Stability, Metabolism, MMPE, Confined Rotational Crops

– USEPA Primary

860.1380 49065802 B.7.0.1 OECD Annex IIA 6.1.1

. Devine H C. (2013); X11393728 (XDE

- 729 methyl) and X11393729 (XDE

- 729): Residue Stability Study in Crops under Frozen Storage
Conditions. DAS Study ID: 110563

. Testing Laboratory: CEM Analytical Services (CEMAS)

. 16

- month Interim Report

. PMRA No. 2286048Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 37 of 56 860.1380 49065803 B.7.0.2 OECD Annex IIA 6.1.1

. Langridge G. (2013); Frozen Storage Stability of Residues of
XDE

- 729 Methyl Ester, XDE

- 729 Acid and X11449757 in Animal Matrices

- Twelve Months Stability Data for Halauxifen

- methyl and XDE

- 729 Acid and Six Months Stability Data for the Relevant Metabolite, X11449757

. DAS Study ID: 110768 Testing Laboratory: CEM Analytical Services (CEMAS)

. PMRA No. 2286049

860.1300 48557789 B.7.1.1 OECD Annex IIA.6.2.1

. Ma, M., Smith, K. P., and Jackson, A. U. A Nature of the Residue Study with [14C]- XR

- 729 Methyl Applied to Wheat with and without the Safener Cloquintocet Mexyl

, Unpublished report of Dow AgroSciences, study ID 101080, 28 Oct 2011, amended report date Au gust 20, 2012

. PMRA No. 2226516

860.1300 48557807 B.7.1.2 OECD Annex IIA.6.2.1

. Rotondaro, S. L., Taylor, J. A., Balcer, J. L., Grotenhuis, A. N., and Graper, L. K. A Nature of the Residue Study with [14C]-XDE

- 729 Methyl Applied to Turnips

, Unpublished report of Dow AgroSciences, study ID 110413, 23 July 2012. PMRA No. 2226517

860.1300 48557791 B.7.2.1 OECD Annex IIA.6.2.3

. Rotondaro, S. L., and Adelfinskaya, Y.A. A Nature of the Residue Study in the Ruminant with [14C]

- XDE

- 729 Methyl Es ter, Unpublished Report of Dow AgroSciences, Study ID 101389, 27 October 2011

. PMRA No. 2226519

860.1300 48557790 B.7.2.2 OECD Annex IIA.6.2.2

. Rotondaro, S. L. and Adelfinskaya, Y. A. A Nature of the Residue Study in the Laying Hen with [14C]

- XDE

- 729 Methyl Ester, Unpublished report of Dow AgroSciences, study ID 101390, 27 October 2011

. PMRA No. 2226518

860.1520 48557812 B.7.7.1 OECD Annex IIA 6.5.3

. Korpalski, S. J. (2012); Magnitude of the Residue of XDE

729 in Wheat Processing Fractions Following Spring Application of GF

- 2685 to Wheat Study Number: 10

- 01459, DAS Study ID. 101557, Testing Laboratory: Eurofins Agroscience Services, Inc., Dow AgroSciences, LLC, JRF America, and GLP Technologies

. PMRA No. 2226530

860.1480 48557802 B.7.8 OECD Annex IIA 6.4.2. Rawle, N.W.: “XDE

- 729 Livestock Feeding Study: Magnitude of Residue in Milk, Muscle, Fat, Liver and Kidney of Lactating Dairy Cattle”; Unpublished Report of Dow AgroSciences (Report ID: CEMR

- 5266), Dow AgroSciences Study Reference ID: 120077; 13 July 2012. PMRA No. 2226529

860.1850 48557813 B.7.9 OECD Annex IIA 6.6

. Rotondaro, S. L. A Confined Rotational Crop Study with [14C]

- XDE

- 729 Methyl Ester

, Unpublished report of Dow AgroSciences LLC, study ID 101635, 09

- DEC

- 2011

. PMRA No. 2226531
Monograph Annex B.7.6: Crop Field Trials

- PMRA Primary

860.1500 48557805

48557806 B.7.6.1 OECD Annex IIA 6.3.1. Kopalski, S. J. (2011); Magnitude and Decline of the Residue
of XDE

- 729 Following Spring application of GF

- 2685 to Wheat. Dow AgroSciences Study no. 101556

. EASI Study no. 10

- 00530

. PMRA no. 2226520

OECD Annex IIA 6.3.1. Kopalski, S. J. (2012); Magnitude of XDE

- 729 Residues
f ollowing Spring Application of GF

- 2685 to Wheat, Dow AgroSciences Study no.
110322

, EASI Study no. 11

- 00495

, PMRA no. 2226523

860.1500 48557810

48557811 B.7.6.2 OECD Annex IIA 6.3.1. Kopalski, S. J. (2012); Magnitude of XDE

- 729 Residues following Spring Application of GF

- 2685 to Barley. Dow AgroSciences Study no.
110321

. EASI Study no. 11

- 00494

. PMRA no. 2226525

OECD Annex IIA 6.3.1. Kopalski, S. J. (2011); Magnitude and Decline of the Residue
of XDE

- 729 Following Spring application of GF

- 2685 to Barley. Dow AgroSciences Study no. 101551

. EASI Study no. 10

- 01460

. PMRA no. 2226528Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 38 of 56 Attachment 2 . NAFTA Field Trial Geographic Representation

Field Trial Numbers and Geographical Locations for Wheat

NAFTA Growing Zones Wheat

Submitted Requested

Canada 1 U.S. 2

1

1A

2 2 1

3

4 1 1

5 5 2 5

5A

5B

6 1 1

7 6 7 5

7A 1 1

8 3 6

9

10

11 1 1

12

13

14 7 10

15

16

17

18

19

20

21

Total 27 20 20

1 : As per DIR98

- 02, Residue Chemistry Guidelines 2: As per OCSPP Series 860 Residue Chemistry Guidelines, Section 860.1500, Table 5Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 39 of 56 Field Trial Numbers and Geographical Locations for Barley

NAFTA Growing Zones Barley

Submitted Requested

Canada 1 U.S.

1 1 1

1A

2

3

4

5, 5A, 5B 3 2 3

6

7 4 2 4

7A 1 1

8

9 1 1

10 1 1

11 1 1

12

13

14 6 12 6

15

16

17

18

19

20

21

Total 18 16 18

1 As per DIR98

- 02, Residue Chemistry Guidelines 2: As per OCSPP Series 860 Residue Chemistry Guidelines, Section 860.1500, Table 5Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 40 of 56 Attachment 3 : Crop Field Trial Data and OECD MRL Calculator Outputs

The OECD MRL Calculator generates MRLs based on mean field trial values. As a result, the
residue values in ppm listed in the tables in this attachment are the means of the two samples
taken at each trial site.

Crop Field Trial Data (Mean Values) and OECD MRL Calculator Outputs
Compound Halauxifen

Methyl Halauxifen

Methyl Halauxifen

Methyl Halauxifen

Methyl Crop Wheat Forage Wheat Hay Barley Hay , Grain, and
Straw Wheat Straw

Region / Country USA/Canada USA/Canada USA/Canada USA/Canada

GAP 0.00875 lb
ai/A 0.00875 lb

ai/A 0.00875 lb

ai/A 0.00875 lb

ai/A
Total number of data (n) 27 27 18 27
Percentage of censored
data 0% 89% 100% 93%

Number of non

- censored
data 27 3 0 2

Lowest residue 0.043 0.010 0.010 0.010 Highest residue 0.385 0.025 0.010 0.013

Median residue 0.139 0.010 0.010 0.010

Mean 0.149 0.011 0.010 0.010
Standard deviation (SD) 0.077 0.004 0.000 0.000

Correction factor for censoring (CF) 1.000 0.407 0.333 0.383

- Highest residue 0.385 0.025 0.010 0.013

- Mean + 4 SD 0.458 0.026 0.010 0.012

- CF x 3 Mean 0.448 0.014 0.010 0.012

Unrounded MRL 0.458 0.026 0.010 0.013

Rounded MRL 0.5 0.03 0.01 0.015

High uncertainty of
MRL estimate due to high
level of censoring. High

uncertainty of
MRL estimate due to high
level of censoring. High

uncertainty of
MRL estimate due to high
level of censoring.

Residues ( ppm ) Residues

( ppm ) Residues

( ppm ) Residues

( ppm )
0.139 0.023 0.010 * 0.013

0.385 0.025 0.010 * 0.010

0.047 0.012 0.010 * 0.010 *

0.081 0.010 * 0.010 * 0.010 *

0.212 0.010 * 0.010 * 0.010 *

0.240 0.010 * 0.010 * 0.010 *Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 41 of 56 Crop Field Trial Data (Mean Values) and OECD MRL Calculator Outputs
Compound Halauxifen

Methyl Halauxifen

Methyl Halauxifen

Methyl Halauxifen

Methyl Crop Wheat Forage Wheat Hay Barley Hay , Grain, and
Straw Wheat Straw

Region / Country USA/Canada USA/Canada USA/Canada USA/Canada

GAP 0.00875 lb
ai/A 0.00875 lb

ai/A 0.00875 lb

ai/A 0.00875 lb

ai/A
0.203 0.010 * 0.010 * 0.010 *

0.139 0.010 * 0.010 * 0.010 *

0.071 0.010 * 0.010 * 0.010 *

0.137 0.010 * 0.010 * 0.010 *

0.172 0.010 * 0.010 * 0.010 *

0.183 0.010 * 0.010 * 0.010 *

0.169 0.010 * 0.010 * 0.010 *

0.158 0.010 * 0.010 * 0.010 *

0.174 0.010 * 0.010 * 0.010 *

0.099 0.010 * 0.010 * 0.010 *

0.043 0.010 * 0.010 * 0.010 *

0.105 0.010 * 0.010 * 0.010 *

0.243 0.010 * 0.010 *

0.240 0.010 * 0.010 *

0.061 0.010 * 0.010 *

0.201 0.010 * 0.010 *

0.138 0.010 * 0.010 *

0.156 0.010 * 0.010 *

0.117 0.010 * 0.010 *

0.067 0.010 * 0.010 *

0.058 0.010 * 0.010 *Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 42 of 56 Attachment 4. International Residue Limit Status



## Halauxifen

- methyl ( 117501 ; 11

- 18

- 2013 )

Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition : US Canada Mexico 2 Codex 3

40 CFR 180. 371

Plants: 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- methoxyphenyl)

- 2

- pyridinecarboxylate 

### NA NA NA

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 2 Codex 3 Barley, grain 

### 0.01 Barley, hay 0.01 Barley, straw 0.01 Wheat, forage 

### 0.5 Wheat, grain 0.1 Wheat, hay 0. 0 3 Wheat, straw 0. 015

Completed: M. Negussie

1 Includes only commodities of interest for this action. Tolerance values are the HED recommendations and not those proposed by the applicant.

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

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

pr ocessed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 43 of 56 Attachment 5 : Halauxifen

- Methyl Metabolites and Degradates

See Attachment 7 for structures of metabolites and degradates

Table B.2. Tabular Summary of Metabolites and Degradates
Chemical
Name Matrix Percent TRR (PPM) 1

Matrices

- Major Residue (>10%TRR) Matrices

- Minor Residue ( <10%TRR)

Parent

Halauxifen

Methyl Wheat Forage: PH 5.0 (0.010)

Wheat Forage: PY 8.3 (0.012)

Wheat Hay: PH 1.0 (0.002)

Wheat Hay: PY 5.4 (0.022)

Wheat Straw: PH 1.2 (0.002)

Wheat Straw: PY 1.9 (0.001)

Turnip Tops: PH 13.5 (0.01 1 )

Turnip Tops: PY 12.2 (0.010 )

Rotational Crops

- -
Ruminant Milk PY

- day 3 : 0.4 (<0.001)

Milk PY

- day 4 : 0.5 (<0.001) Kidney PY: 0.6 (<0.001)

Poultry Skin w ith Fat PH: 0.5 (<0.001)

Rat <5% of the AD in excreta

Water ND

- 97 %

Halauxifen

Methyl
Glucose Conjugate Turnip Tops: PH 2 6.4 (0.02 1 )

Turnip Tops: PY 2 8.7 (0.02 4 )

Rotational Crops

- -
Ruminant

- - Poultry

- -

Rat

- -

Water

- - Halauxifen

Methyl

N

- Glucuronic
Acid Conjugate Rotational Crops

- -

Ruminant Milk PY

- day 3: 3.5 (<0.001)

Milk PY

- day 4: 4.2 (<0.001)

Poultry

- -

Rat

- -

Water

- -
XDE

- 729 Acid Wheat Forage: PH 1.6 (0.003)

Wheat Forage: PY 1. 9 (0.00 3 )

Wheat Hay: PH 1.7 (0.004)

Wheat Hay: PY 1.8 (0.007)

Wheat Straw: PH 1.2 (0.002)Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 44 of 56 Wheat Straw: PY 1.8 (0.001)

Turnip Tops: PH 3. 1 (0.00 2 )

Turnip Tops: PY 3. 5 (0.00 3 )

Rotational Crops

- -
Ruminant Kidney PY: 34.4 (0.014) Renal Fat PH: 44.8 (0.007) Liver PH: 12.1 (0.009) Kidney PH: 36.7 (0.044) Milk PY

- day 3: 2.0 (< 0.001)

Milk PY

- day 4: 3.6 (<0.001) Liver PY: 5.8 (0.002)

Poultry Skin w/ Fat PH: 26.0 (0.044) Liver PH: 6.3 (0.003) Liver PY: 5.5 (0.002)

Rat ND ND

Water ND

- 99%

XDE

- 729 Acid
Glucose Conjugate Turnip Tops: PH 12.5 (0.010)

Turnip Tops: PY 12.6 (0.010)

Rotational Crops

- -
Ruminant

- - Poultry

- -

Rat

- <5% of the AD in excreta

Water

- - X11406790 Wheat Forage: PH 2.6 (0.005)

Wheat Forage: PY 3.8 (0.006)

Wheat Hay: PH 0.5 (0.001)

Wheat Hay: PY 0.8 (0.003)

Wheat Straw: PH 0.9 (0.002)

Wheat Straw: PY 0.8 (0.001)

Turnip Tops: PH 2.2 (0.002)

Turnip Tops: PY 1.5 (0.001)

Rotational Crops

- -
Ruminant Milk PY

- day 3: 2.5 (<0.001)

Milk PY

- day 4: 0.3 (<0.001) Kidney PH: 1.2 (0.002) Kidney PY: 0.3 (<0.001) Liver PY: 8.8 (0.003)

Poultry Skin with Fat PH: 4.3 (0.001) Liver PH: 5.7 (0.003)

Rat

- -

Water 0.5%

- 3 3 %

X11406790

Glucose Conjugate Wheat Forage: PH 2.6 (0.005)

Wheat Forage: PY 1.4 (0.002)

Wheat Hay: PH 4.4 (0.010)

Wheat Hay: PY 4.9 (0.020)Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 45 of 56 Wheat Straw: PH 3.2 (0.006)

Wheat Straw: PY 3.0 (0.002)

Rotational Crops

- -
Ruminant

- - Poultry

- -

Rat

- -

Water

- - X11406790

Glucose Malonyl Conjugate Wheat Forage: PH 10.3 (0.021)

Wheat Forage: P Y 5.9 (0.009)

Wheat Hay : PH 5.0 (0.012)

Wheat Hay : P Y 4.8 (0.020)

Wheat Straw : PH 5.2 (0.010)

Wheat Straw : P Y 3.7 (0.002)

Turnip Tops: PH 5.9 (0.005)

Turnip Tops: PY 7.2 (0.006)

Rotational Crops

- -
Ruminant

- - Poultry

- -

Rat

- -

Water

- - X11406790

Glucuronic
Acid Conjugate Rotational Crops

- -

Ruminant Milk PY

- day 3: 40.7 (0.005)

Milk PY

- day 4: 24.5 (0.002) Kidney PH: 5.9 (0.007)

Poultry

- -

Rat

- -

Water

- - X11406790

Sulfate Conjugate Rotational Crops

- -

Ruminant Milk PY

- day 3: 21.8 (0.003)

Milk PY

- day 4: 12.5 (0.001) Kidney PH: 0.8 (0.001)

Poultry Skin with Fat PH: 12.3 (0.00 2 )

Liver PH: 14.5 (0.00 7 ) Liver PY: 8.3 (0.004)

Rat

- -

Water

- - X11449757 Wheat Forage: PH 5.1 (0.010)

Wheat Forage: P Y 4.7 (0.007)

Wheat Hay: PH 1.9 (0.005)

Wheat Hay : PY 1.9 (0.008)

Wheat Straw: PH 2.0 (0.004)

Wheat Straw : PY 1.7 (0.001)

Rotational Crops

- -Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 46 of 56 Ruminant Renal Fat PH: 17.4 (0.003) Liver PH: 62.0 (0.048) Liver PY: 31.9 (0.010) Kidney PH: 14.7 (0.018) Kidney PY: 14.4 (0.006)

Milk PY

- day 3: 10.1 (0.001)

Milk PY

- day 4: 21.9 (0.002)

Poultry Liver PH: 32.3 (0.015) Skin with Fat PH: 2.9 (<0.001)

Rat <5% of the AD in excreta

Water 3%

- 77%

X11449757
Sulfate Conjugate Rotational Crops

- -

Ruminant Kidney PH: 18.3 (0.022) Kidney PY: 10.4 (0.004) Renal Fat PH: 9.5 (0.002)

Poultry Skin with Fat PH: 0.4 (<0.001) Liver PH: 0.9 (<0.001)

Rat <5% of the AD in excreta

Water

- - X11449757
Glucuronide Conjugate Rat

- <5% of the AD in excreta

Degradate 1 Water 20%

- 41%
Degradate 2 Water 8%

- 13%
Degradate 4 Water 0.7%

- 15%
Degradate 10 Water ND

– 13%
Degradate 11 Water ND

– 16%
Degradate 14 Water ND

– 12%

The wheat metabolism studies included use of a safener.
The Turnip samples were taken at 14 days after treatment No metabolites were identified in the rotational crop study. TRR in all commodities was 0.001 ppm or less
<5% of the AD: <5% of the administered doseHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 47 of 56 Attachment 6: Proposed Metabolic Pathways and Environmental Degradation Scheme

6.a. Proposed Metabolic Pathway of Halauxifen

- Methyl in WheatHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 48 of 56 6.b

. Proposed Metabolic Pathway of Halauxifen

- Methyl in Turnips

XDE

- 729 Methyl

X11406790 X11393729

X11406790 glucose conjugate (proposed,

not observed)

OR X11393729 glucose conjugate

X11406790 malonyl

- glucose conjugate XDE

- 729 Methyl

glucose conjugate (2 anomers)Halauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 49 of 56 6.c

. Proposed Metabolic Pathway of Halauxifen

- Methyl in GoatsHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 50 of 56 6.d

. Proposed M etabolic P athway of Halauxifen

- Methyl in HensHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 51 of 56 6.e

. Proposed Metabolic Pathway of XDE

- 729 Acid in RatsHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 52 of 56 6.f

. Proposed Halauxifen

- Methyl Environmental Transformation SchemeHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 53 of 56 Attachment 7

. Structures of Important Metabolites and Degradates Found in Metabolism Studies, Confined Rotational Crop Study, Crop Field Trials, Livestock Feeding Studies, and Environmental Fate Studies

Structures of Halauxifen

- Methyl Metabolites and Degradates



### Code Name Chemical Abstracts Name Structure Where Found

Halauxifen

methyl methyl 4

- amino

- 3

- chloro

- 6

- (4

-

chloro

- 2

- fluoro

- 3

- methoxyphenyl)pyridine

- 2

- carboxylate 

### Metabolism: wheat, turnips, poultry, drinking water

Env fate: hydrolysis, soil photolysis

H alauxifen

methyl
N

- glucose conjugate (anomers) methyl 3

- chloro

- 6

- (4

- chloro

- 2

-

fluoro

- 3

- methoxy

- phenyl)

- 4

- [[3,4,5

- trihydroxy

- 6

- (hydroxymethyl)tetrahydropyran

- 2

- yl]amino]pyridine

- 2

- carboxylate (anomers = α

- and β

conjugated glucose) Metabolism: turnips

H alauxifen

methyl
N

- gluc uronic
acid conjugate 6

- [[3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

-

methoxy

- phenyl)

- 2

- methoxycarbonyl

- 4

- pyridyl]amino]

- 3,4,5

- trihydroxy

- tetrahydropyran

- 2

- carboxylic acid



### or isomer Metabolism:
ruminants

XDE

- 729
Acid

4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

-

fluoro

- 3

- methoxy

- phenyl)

- pyridine

2

- carboxylic acid

Rat metabolism DER: XR

- 729
Parent 

### Metabolism: wheat, turnips, ruminants, poultry, rats

, drinking water

Env fate: hydrolysis, soil photolysis,
anaerobic soil
metabolismHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 54 of 56 Structures of Halauxifen

- Methyl Metabolites and Degradates



### Code Name Chemical Abstracts Name Structure Where Found

XDE

- 729
Acid gl ucose conjugate [3,4,5

- trihydroxy

- 6

-

(hydroxymethyl)tetrahydropyran

- 2

- yl] 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- methoxy

phenyl)pyridine

- 2

- carboxylate

or

3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

- methoxy

- phenyl)

- 4

- [[3,4,5

- trihydroxy

- 6

- (hydroxymethyl)tetrahydropyran

- 2

- yl]amino]pyridine

- 2

- carboxylic acid or Metabolism: turnips

X11406790 methyl 4

- amino

- 3

- chloro

- 6

- (4

-

chloro

- 2

- fluoro

- 3

- hydroxyphenyl)pyridine

- 2

- carboxylate 

### Metabolism: wheat, turnips, ruminants, poultry, drinking water

X11406790 glucose conjugate See proposed metabolic profile for wheat Metabolism:
wheat

X11406790 glucose

malonyl conjugate See proposed metabolic profile for wheat Metabolism:
wheatHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 55 of 56 Structures of Halauxifen

- Methyl Metabolites and Degradates



### Code Name Chemical Abstracts Name Structure Where Found

X11406790
N

- or O

glucuronic
acid conjugate 6

- [[3

- chloro

- 6

- (4

- chloro

- 2

- fluoro

- 3

-

hydroxy

- phenyl)

- 2

- methoxycarbonyl

- 4

- pyridyl]amino]

- 3,4,5

- trihydroxy

tetrahydropyran

- 2

- carboxylic acid or
6

- [3

- (4

- amino

- 5

- chloro

- 6

- methoxycarbonyl

- 2

- pyridyl)

- 6

- chloro

2

- fluoro

- phenoxy]

- 3,4,5

- trihydroxy

tetrahydropyran

- 2

- c arboxylic acid



### or Metabolism:
ruminants

X11449757 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

-

fluoro

- 3

- hydroxyphenyl)

- pyridine

2

- carboxylic acid

Rat metabolism DER: O

- demethyl

XR

- 729 

### Metabolism: wheat, ruminants, poultry, rats drinking water

Env. fate:
anaerobic soil metab., aerobic aquatic metab.

X11449757
Sulfate Conjugate 4

- amino

- 3

- chloro

- 6

- (4

- chloro

- 2

-

fluoro

- 3

- sulfoxy

- phenyl)pyridine

- 2

- carboxylic acid

Rat metabolism DER: sulfate conjugate of O

- demethyl

- XR

- 729 

### Metabolism: ruminants, poultry, rats

X11449757
Glucuronide Conjugate Rat metabolism DER: glucuronide

conjugate of O

- demethyl

- XR

- 729 

### See proposed metabolic profile for r at s Metabolism:

rats

X11449757 Acyl
Glucuronide Conjugate Rat metabolism DER: acyl

glucuronide conjugate of O

demethyl

- XR

- 729 

### See proposed metabolic profile for rats Metabolism:

rats

Degradate 1 Unknown

Unknown Metabolism: drinking water

Env. fate:

aqueous photolysisHalauxifen

- Methyl Summary of Analytical Chemistry and Residue Data DP Number D 416127



### Page 56 of 56 Structures of Halauxifen

- Methyl Metabolites and Degradates



### Code Name Chemical Abstracts Name Structure Where Found
Degradate 2 Unknown

Unknown Metabolism: drinking water

Env. fate:

aqueous photolysis

Degradate 4 Unknown

Unknown Metabolism: drinking water

Env. fate:

aqueous photolysis

Degradate 10 Methyl 4

- amino

- 6

- (4

- chloro

- 2

-

fluoro

- 3

- methoxy

- phenyl)

- 3

- hydroxy

- pyridine

- 2

- carboxylate 

### Metabolism: drinking water

Env. fate:

aqueous photolysis

Degradate 11 Methyl (2E)

- 2

- (4

- chloro

- 2

- fluoro

- 3

-

methoxy

- benzoyl)iminoacetate 

### Metabolism: drinking water

Env. fate:

aqueous photolysis

Degradate 14

2

- [(E)

- (4

- chloro

- 2

- fluoro

- 3

-

methoxy

- phenyl)methyleneamino] acetaldehyde 

### Metabolism: drinking water

Env. fate:

aqueous photolysis