UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 7111/2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Subject: Halauxifen-Methyl. Petition for the Section 3 Registration and the Establislunent of 

Tolerances on Wheat, Barley, and Triticale. Summary of Analytical Chemistry and 

Residue Data 

PC Code: 11750 I 

Decision Nos.: 470169 

Petition No.: 2E8086 

Risk Assessment Type: NA 

TXRNo.: NA 

MRID Nos.: 48557789-48557796, 48557802, 

48557807, 48557812,48557813,48557865, 

48557898, 48901101,49065802, 49065803 

DPBarcode: 0 416127 

Registration Nos.: 62719-AAE, AAG, AAN, AAR, 

AAU 

Regulatory Action: Section 3 Registration 

CaseNo.: NA 

CAS No.: 943831-98-9 

40CFR: NA 

From: Douglas A. Dotson, Ph.D., Chemist IJ. ~~ RABII 

Health Effects Division (7509P) 

Through: P. Yvonne Barnes, Chemist -j? ~ '"$ :> _ L 

Michael Doherty, Ph.D., Senior Chemist ~ ~~q 

HED Chemistry Science Advisory Council (ChemSAC) 

Health Effects Division (7509P) 

To: Maggie Rudick/Kable Bo Davis, PM Team 25 

Herbicide Branch 

Registration Division (7505P) 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number 0416127 

Table of Contents 

1.0 Executive Summary ....................................... .............................................................. ..... 4 

2.0 Regulatory Recommendations ......................................................................................... 5 

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

2.2 Tolerance Considerations ... .... ............... .......................................... .......... ......... .......... 5 

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

2.2.2 Recommended Tolerances ...................... .................................................... 7 

2.2.3 Revisions to Proposed Tolerances ...... ................................ ............. ........... 8 

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

2.3 Label Recommendations ....... ........... ................... ............ .... ......................................... 8 

3.0 Introduction ... ................................................................................................................... .. 9 

3.1 Chemical Identity ............................................................ ............................................. 9 

3.2 Physical/Chemical Characteristics ................................................................... .......... 10 

3.3 Pesticide Use Pattern/Directions for Use (860. 1200) ........................ .................. ...... 10 

4.0 Metabolite/Degradate Residue Profile .................................................................... ...... 11 

4.1 Nature ofthe Residue .......................... ........ ............................................................... 11 

4.1.1 Summary of Plant Metabolism (860.1300) ....... .... .... ................................ 12 

4.1.2 Summary of Confmed Rotational Crops (860. 1850) ................................ 14 

4.1.3 Summary of Livestock Metabolism (860.1300) ....................................... 15 

4.1.4 Summary of Metabolites and Degradates ................................................. 16 

4.2 Comparison of Metabolic Pathways .............................................. ............................ 17 

4.3 Residues of Concern Summary and Rationale ........................................................... 17 

5.0 Residue Profile ................................................. ....................... ............ ............................ 19 

5.1 Residue Analytical Methods (860.1340) ............................................................ ..... .. 19 

5.1.1 Data Collection Methods ........... ............................................................... 19 

5.1.2 Multi-Residue Methods (860.1360) .......... ................................................ 21 

5.1.3 Tolerance Enforcement Methods .................................. ............................ 22 

5.1.4 Submittal of Analytical Reference Standards (860.1650) ........................ 23 

5. 1.5 Storage Stability ............................................ .... .... .... ........ ........................ 24 

5.2 Residue Data ................................... .... .... .... ... ............................................................ 25 

5.2.1 Crop Field 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 Meat, Milk, Poultry, and Eggs (860.1480) ............................................... 30 

5.2.4.1 Dietary Burden ........................ ...................................................... ... 30 

5.2.4.2 Estimated Secondary Residues in Livestock .................................... 31 

5.2.5 Food Handling (860.1460) ........ ................................................................ 35 

5.2.6 Water, Fish, and Irrigated Crops (860.1400) .................................... ........ 35 

6.0 Tolerance Derivation .......................... ............................................................................ 35 

7.0 ChemSAC Reference ......................................... .................................... ...................... ... 35 

Attachments .... ................................................................................................................. 36 

I. Summary of Submitted Residue Chemistry Studies ........................... ................. ..... ... 36 

2. NAFTA Field Trial Geographic Representation ..... ........ ................ ............................. 38 

3. Field Trial Data and OECD MRL Calculator Outputs ..................... .. .... ..................... 40 

4. International Residue Limits Table ............................. .... ............................. ................ 42 

Page 2 of 56 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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5. Summary Table of Important Metabolites and Degradates......................................... 43

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 Environmental Transformation Scheme ............................................ 52

7. Chemical Structures of Important Metabolites............................................................ 53
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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 petitioner for this new active ingredient is Dow 

AgroSciences, LLC. The science reviews are being performed jointly 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 these 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, GF2686 contains 20.9% halauxifen-methyl and 20% florasulam, and GF-2688 contains 1.6% 

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

halauxifen-methyl only.

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 metabolism 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 study. HED has reviewed 

these 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 assessment 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).

An adequate analytical method is available for enforcement of the tolerances in plant 

commodities. The tolerance enforcement method is a liquid chromatography with tandem mass 

spectroscopy (LC-MS/MS) method that was adequately validated. It has a limit of quantitation 

of 0.01 ppm.

The petitioner 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 Agreement (NAFTA) 

growing zones, and the studies are supported by adequate storage stability and analytical 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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methods data. The Organization for Economic Co-operation and Development (OECD)

maximum residue limit (MRL) calculation procedures were used to determine the recommended 

tolerances.

The petitioner submitted an adequate cattle feeding study that can be used to determine the need 

for tolerances for ruminant commodities. HED has determined that there is no reasonable 

expectation of finite residues in ruminant or poultry commodities. As a result, tolerances are not 

needed for them.

2.0 Regulatory Recommendations

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 

document.

2.1 Data Deficiencies/Data 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 deficiencies associated with this tolerance petition.

2.2 Tolerance Considerations

2.2.1 Analytical Enforcement Methods

Plant Commodity Enforcement Method

As the analytical enforcement method for halauxifen-methyl in plant matrices, the petitioner

proposed the method in Report Number 110004. With this method, residues of halauxifenmethyl 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 LC-MS/MS. Ion transitions for 

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

XDE-729 acid are 331/250 (quantitation) and 331/285 (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 determined 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 method 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 D416127

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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 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. As a result, the FDA multiresidue test procedures are not suitable for the 

regulatory analysis of halauxifen-methyl and XDE-729 acid.

QuEChERS Multiresidue Method for Plant Commodities

The 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 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 C18 column coupled with positive-ion electrospray tandem mass spectrometry 

(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 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 method 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 the method.
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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2.2.2 Recommended Tolerances

HED recommends that 40CFR be amended by establishing tolerances for the plant commodities 

listed in the table below. The 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)

Recommended 

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 0.50 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 for 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)

Recommended 

Tolerance 

(ppm)

Comments

(correct commodity definition)

cattle, fat 0.01 None

cattle, meat 0.01 None

cattle, 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

milk 0.01 None
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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Table 2. Tolerance Summary for Halauxifen-methyl

Commodity

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance 

(ppm)

Comments

(correct commodity definition)

sheep, fat 0.01 None

sheep, meat 0.01 None

sheep, meat byproducts 0.01 None

2.2.3 Revisions to Proposed 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, it included the metabolites XDE-729 acid as a residue of 

concern. HED subsequently determined that 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. The U.S., Canada, and Australia, all agreed to use the OECD MRL 

calculation procedures for this tolerance petition. In addition, the three countries are in 

agreement 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.

The tolerances/MRLs that are 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 is 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 commodities. 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 straw, 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 

MRLs in these situations. As a result, Canada is establishing LOQ MRLs 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 the maximum seasonal application 

rates. 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 growing season. Some of the end-use products proposed for 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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 coformulated 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 C14 H11O3N2Cl2F 

Molecular Weight 345.16

CAS Name Methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-

methoxyphenyl)-2-pyridinecarboxylate 

CAS Number 943831-98-9
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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 KOW Log KOW

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 (pKa) 2.84 @ 20°C 5.11 @ 21.9°C

3.3 Pesticide Use Pattern/Directions for Proposed Uses (860.1200)

Halauxifen-methyl 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 labels do not specify the maximum number of applications that may be made. The 

recommended single application rate is approximately 0.005 lb ai/A. For GF-2685, the 

maximum seasonal application rate is 0.0091 lb ai/A. These application rates indicate that the 

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 is 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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 either 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, soybean, 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

Application Rate

(lb ai/A)

Max No. 

Applic. Per 

Seasonc

Max. Seasonal 

Applic. Rate

(lb ai/A) PHId

Use 

Directions 

and 

Limitationse

Ground 

and Aerial 

Equipment

GF-2685 WG

(62719-AAG) 0.0045 2 0.0091

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, 2013, 

D416123, D. Dotson, 7/11/2014

Halauxifen-methyl: Report of the Residues of Concern Knowledgebase Subcommittee 

(ROCKS), D416125, E. Holman, 5/20/2014 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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48557789.DER.docx: Wheat Metabolism Study

48557807.DER.docx: Turnip Metabolism Study

48557791.DER.docx: Goat Metabolism Study

48557790.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 wheat metabolism study, a single foliar application of halauxifen-methyl formulated as an 

emulsifiable concentrate (EC) with and without a safener was 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 both 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 resulting 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), mature straw (0.06-0.35 ppm), and grain (≤ 0.004 ppm)

halauxifen-methyl equivalents.

 

The majority of the residues were found to be readily extractable with a mild procedure, and 

minimal additional residues were extractable with stronger procedures. Typically 66-81% of the 

residue was extracted from forage, hay, and straw samples and was further characterized by high 

performance liquid chromatography (HPLC).

 

The 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), X11861662 (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), X11861662 (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 D416127

Page 13 of 56

The pectin substances in the non-extractable residue were solubilized using ethylenediaminetetraacetic 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 weighed and 

used in the acid-detergent fiber (ADF) isolation 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 the reflux period, the solids were removed by 

vacuum filtration. The remaining solids (the ADF fraction) were weighed and combusted. The 

ADF fraction consisted of cellulose and included radioactivity encapsulated by cellulose. The 

total amount of radioactivity in the liquid fraction, which included hemicellulose and dissolved 

plant proteins, was determined by LSC analysis. In 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 associated 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 demonstrated 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 

radiolabeled carbon into natural plant constituents, such as pectin and lignin. The low 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. Mature PH-labeled roots and tops sampled at a PHI of 14 

days contained 0.001 and 0.091 ppm halauxifen-methyl equivalents, respectively. The PYlabeled 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 

mature 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 mg equiv./kg), glucose conjugate of XDE-729 acid
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 14 of 56

(13-14% of the TRR, 0.012-0.015 mg equiv./kg), a malonyl glucose conjugate of X11406790 

(7% of the TRR, 0.006-0.008 mg equiv./kg), two N-glucose conjugates of halauxifen-methyl 

(anomer 1: 15-17% of the TRR, 0.014-0.019 mg equiv./kg, anomer 2: 9-10% of the TRR, 0.009-

0.010 mg equiv./kg), and X11406790 (2-3% of the TRR, 0.002 mg equiv./kg). The levels of the 

radiolabeled metabolites were the same irrespective of radiolabel, indicating no evidence of 

bridge cleavage.

Individual metabolite 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 the metabolic pathway 

observed in wheat.

4.1.2 Summary of Confined Rotational Crops (860.1850)

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). Radish,

lettuce, and wheat were sown at 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 interval, 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 contained less than 0.01 ppm halauxifen-methyl equivalents, and were therefore not 

analyzed further.

In practical use, halauxifen-methyl 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-methyl, such that the 

soil will only receive a portion of the application. TRR in the rotated crops were below 0.01 

ppm halauxifen-methyl equivalents over the three plant-back intervals. Because of the very low 

TRR levels, none of the residues in tissue samples were characterized further.

Table 6. TRR in Confined Rotational Crop 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 <LOQb 64 <LOQb

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 <LOQ
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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Table 6. TRR in Confined Rotational Crop 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 detectable levels of halauxifen-methyl in any raw agricultural commodity. 

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 trials 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 at a feeding level of approximately 11

ppm dry feed per day (35x the dairy cattle dietary burden). Halauxifen-methyl was primarily

eliminated in the feces (40.9-45.9% of the dose (both labels), including 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-methyl 

equivalents. Analyses of milk showed the residue levels reached a plateau during the dosing 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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-methyl (or isomer), the 

sulfate conjugate of X11406790 (or isomer), and X11406790. Less than 0.001 ppm halauxifenmethyl was detected in milk or any edible tissue. Generally, the above components totaled 

greater than 61% of the residues in milk and tissues. The remaining residue was characterized as 

multi-component. In the edible matrices, metabolite X11449757 was observed at the highest 

level, 0.048 ppm halauxifen-methyl equivalents (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 XDE-729

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

halauxifen-methyl and its metabolites can conjugate with 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). XDE-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, metabolism proceeds through demethylation of the methyl ester (forming XDE-729

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

can conjugate with sulfate. In the edible matrices that were analyzed, metabolite X11449757 

was typically observed at the highest level.

4.1.4. Summary of Metabolites and Degradates

The 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 nature 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 for 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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 halauxifen-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 undergoes 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., 

-OCH3 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 is 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 is converted to a hydroxyl group, the compound becomes a phenol (the 

X11406790 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 various 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 extensive 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 

environmental 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 recommended 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 D416127

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Table 7. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression

Matrix Residues Included in Risk Assessment Residues Included in Tolerance 

Expression for Compliance 

Monitoring

Plants Primary Crop Halauxifen-methyl Halauxifen-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, 

5/20/2014).

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 acid) 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, ROCKS 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 compared 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 

presence 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 halauxifen-methyl (Log P = 3.07) or XDE-729-acid (Log P=3.52). Based 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 D416127

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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 trials. 

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 residues 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 considered 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 analyzed, 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 an LC-MS/MS method 

described in Dow Report Number 110005. With this method, residues are extracted 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. One-hundred microliters of a glycerin:methanol solution (10:90 w/v) 

containing a mixed (halauxifen-methyl M+4 and XDE-729 acid M+4) stable-isotope internal 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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:water (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 XDE729 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 forage), dry crops (the grain, hay, and straw of barley 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 starch. The method was successfully validated for 

linearity, precision, accuracy, and LOQ, for both halauxifen-methyl and XDE-729 acid.

To determine the extraction efficiency of the analytical method, samples of wheat containing 

incurred residues from a metabolism 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 

determination 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 types and wheat processed commodities for linearity, 

precision, accuracy, and LOQ, for both halauxifen-methyl and XDE-729 acid.

Data Collection Method for Livestock Commodities

As part of the cattle feeding study, residues 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 homogenizing 

the sample in 20.0 mL of an acetonitrile/water (80:20, v/v) solution. Residues were extracted 

from a 1.0-gram portion of milk, fat, cream, or skim milk by homogenizing 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 acetonitrile/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 analyzed by LC-MS/MS. The LOQ for halauxifen-methyl, XDE-729 acid, and 

X11449757 in all matrices was 0.01 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 D416127

Page 21 of 56

The method was 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 (860.1360)

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 multiresidue 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 Analytical 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.

The FDA multiresidue test procedures are not suitable for the regulatory analysis of halauxifenmethyl and XDE-729 acid. There are no outstanding data deficiencies associated with the 

multiresidue analytical method.

QuEChERS Multiresidue Method for Plant Commodities

The 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 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 C18 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 of 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 D416127

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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 XDE729 acid were extracted 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 solidphase extraction (SPE) cartridge. After elution from the 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 positiveion electrospray 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+6 (X11901295) is 351/256 (quantitation) and the ion transition for XDE729 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 XDE729 acid in agricultural 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 

Pyxant 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 method 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 enforcement 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 23 of 56

method for X11449757 and an ILV for the method.

Conclusions 

HED has determined that the method described in Dow Report Number 110004 is acceptable as 

an analytical enforcement method, as defined in SOP No. ACB-019 (9/15/2008). 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. 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.

The FDA multiresidue test procedures are not suitable for the regulatory analysis of halauxifenmethyl and XDE-729 acid. The 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 adequate 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

Fort 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 D416127

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 water 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 -18oC and analyzed at storage intervals of 0, 97 (halauxifen-methyl only), 120, 

174, 366, and 489 days.

The final extracts were analyzed for residues of halauxifen-methyl and XDE-729 acid 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 residues of halauxifen-methyl and XDE-729 acid are stable

in a variety of crop matrices when stored frozen at ≤-18°C over the course of 489 days (16 

months). Acceptable methods for quantitation 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-729 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 frozen 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 residues 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 D416127

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The LOQ was confirmed to be 0.01 ppm for the three compounds in all the livestock matrices 

tested (bovine muscle, milk, poultry liver, and 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. Residues 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 14 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 91 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

Field 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 trial location, consisting of 

one untreated and one treated plot, halauxifen-methyl (GF-2685, a 10% 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). Application rates were 0.0087-0.0099 lbs halauxifenmethyl/A. Duplicate samples were collected from the treated plots, and a single sample was 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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collected from the untreated control plots. Forage samples were cut and collected, and hay 

samples were cut 1 day (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. Samples 

of straw and grain were collected at early maturity, at PHIs of 42-73 days (BBCH87-97, with the 

exception 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.

Residue decline behavior was evaluated at two sites from the 2010 trials. Forage 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.

Residues of halauxifen-methyl were <0.01 ppm in all samples of wheat grain. Residues ranged 

from 0.036 ppm to 0.389 ppm in wheat forage, <0.01 ppm to 0.026 ppm in wheat hay, <0.01

ppm to 0.013 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 maximum 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

Barley 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 trial location, consisting of one untreated and one treated plot, halauxifen-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). Application 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 DAT (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 was included in all spray mixtures. Residue decline behavior was evaluate at two sites 

from the 2010 trials. Hay 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 was 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 27 of 56

separated 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 nonquantifiable 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 0.23 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 ai/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 HAFT1 Median Mean.

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. Blank 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 setting 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 Table 1 of this document.

Field Trial Geographic Distribution

The field trial geographic distribution was adequate for wheat and barley. The table in 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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 recommended 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; however, 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 wheat 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 were 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 it is unlikely 

that crops rotated into wheat fields treated with halauxifen-methyl at 0.009 lb ai/A would have

detectable levels of halauxifen-methyl or metabolites in any raw agricultural commodity. 

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 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, soybean, and sunflower. Other crops not listed on 

the label have a 15-month rotation interval. The 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. One plot was 

untreated, one plot was treated at the 1x proposed use rate, and one plot was treated at an 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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exaggerated use rate (5x). The 1x and 5x plots were located side-by-side. The test material was 

GF-2685, a WDG containing halauxifen-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 halauxifen-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 0.0089 lb ae/A halauxifenmethyl in spray volumes of 20.4 GPA (191 L/ha). A safener and an adjuvant (LASER, a 

paraffinic mineral oil and surfactant blend) were 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 fractions, 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 the method described in Dow AgroSciences 

Report Number 110005, an LC-MS/MS method that determines residues of halauxifen-methyl

and XDE-729 acid. Acceptable method validation and concurrent recoveries were reported for 

each analyte for grain, total bran, whole meal flour, whole grain bread, shorts, germ, aspirated 

grain fractions, 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 processed fractions was 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 as well as in all processed 

commodities. As a result, processing factors were not determined for any of the processed 

commodities.

Conclusions to Processing Study

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, residues 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 D416127

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5.2.4 Meat, Milk, Poultry, and Eggs (860.1480)

Reference: 48557802.DER.docx. Cattle 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 expected to be present in poultry commodities.

5.2.4.1 Dietary Burden

Dietary burdens 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 considered to be maximum reasonably 

balanced diets (MRBDs) because for each of the three feed 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, CC 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 = 

[(residue) x (% in diet)] for poultry and swine.

As can be seen in the following table, the dietary burdens for beef cattle, dairy cattle, swine, and 

poultry are 0.012, 0.32, 0.002, and 0.0075 ppm, respectively.

Table 9. Calculation of Dietary Burdens of Halauxifen-Methyl Residues to Livestock.

Feedstuff Type1 % Dry 

Matter2 % Diet2

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 0.002247
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 31 of 56

Table 9. Calculation of Dietary Burdens of Halauxifen-Methyl Residues to Livestock.

Feedstuff Type1 % Dry 

Matter2 % Diet2

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 % diet) for beef and dairy cattle

Contribution = ([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 containing the 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. and 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 fed halauxifen-methyl at the 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 (16 cows).

As discussed above, the dietary burden for dairy cattle is 0.32 ppm and that for beef cattle is 

0.012 pm. The dose rates represent 3.1x, 9.7x, and 49x, respectively, the dietary burden for dairy 

cattle and 83x, 260x, and 1,300x, respectively, the dietary burden for beef cattle. The dose rates 

used in the dairy cattle feeding study are considered to be adequate because the lowest dose level 

is sufficiently close to the dietary burden, and residues in cattle tissues were generally nondetectable at even the highest feeding level. In the few samples that had detectable residues, the 

levels 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 residues following withdrawal of the test item from the 

diet.
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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 was 0.01 ppm halauxifen-methyl equivalents. The LOD for each of the analytes in 

these commodities was 0.003 ppm halauxifen-methyl equivalents. and 0.01 ppm halauxifenmethyl equivalents, respectively. Overall average procedural recoveries 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 perirenal fat) ranged from 

89% to 105%.

At all dose levels, residues of halauxifen-methyl and XDE-729 acid were below the LOQ of 0.01 

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

and perirenal fat. At the lower two dose levels, residues 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 these commodities, with the exception of a single residue of 0.012 ppm halauxifenmethyl equivalents in mesenteric fat and a single residue of 0.014 ppm halauxifen-methyl 

equivalents in perirenal fat.

Residues of X11449757 above the LOQ transferred into liver 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 regression analysis was 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 depuration (Day 31 of the study). At 

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 halauxifenmethyl equivalents).

Table 10. Mean Residues in Whole Milk from Cows During Dosing for at 

Least 28 days with Halauxifen-Methyl (ppm)

Feeding Levels

(ppm)

Halauxifen-methyl XDE-729 Acid X11449757

1.0

3.1

15.6

<0.01

<0.01

<0.01

<0.01

<0.01

<0.01

<0.01

<0.01 

<0.01 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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Table 11. 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 burdens calculated above were used to 

determine whether or not tolerances are needed for livestock commodities. As stated above, the 

feeding levels in the cattle feeding study turned out to be approximately 3.1x, 9.7x, and 49x the 

dietary burden for dairy cattle and 83x, 260x, and 1,300x 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 tolerance 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 was 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 tissues and milk had residue levels that were not quantifiable. The tissueto-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 12). 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 34 of 56

As an example, in 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, 0.01115 ppm, is the tissue-to-feed ratio. When this value was multiplied by the 

dietary burden of 0.32 ppm, the maximum residue expected was found to be 0.0036 ppm.

Table 12. 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 <0.00064 0.318652 <0.00020

Muscle (cattle) 15.6 ND (<0.003) <0.00019 0.318652 <0.00006

Liver (cattle) 15.6 0.174 0.011154 0.318652 0.00355

Kidney (cattle) 15.6 0.053 0.000882 0.318652 0.00028

Fat (subcutaneous) 15.6 <0.01 0.003397 0.318652 0.00108

Fat (mesenteric) 15.6 <0.01 <0.00064 0.318652 <0.00020

Fat (perirenal) 15.6 <0.01 <0.00064 0.318652 <0.00020

* 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, tolerances are not needed for them 

either. As a result of the low dietary burden, 0.0020 ppm, and the low transfer of residues to 

livestock tissues, there 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. In 

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 account 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 expected 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 study is adequate and can be used to determine the need for tolerances for

ruminant commodities. No data deficiencies are associated with the cattle feeding study. Based 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 35 of 56

on the dietary burdens that were constructed and the results of the cattle feeding study and the 

hen metabolism study, tolerances are not needed for livestock commodities. There is no 

reasonable expectation of finite residues in livestock commodities (40CFR §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 Crops (860.1400)

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

6.0 Tolerance Derivation

The OECD MRL calculation procedures were used to determine the tolerances for all 

commodities. The calculator 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 tolerances. The individual spreadsheets for the various commodities can be found 

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 Outputs

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 Metabolites
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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 AgroSciences 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 SolidPhase 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 Mass 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 Bovine 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). Independent 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. PMRA 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 MultiResidue 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. 2286048
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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 August 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 Ester, 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 XDE729 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 

following 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. 2226528
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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

Canada1 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 5
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 39 of 56

Field Trial Numbers and Geographical Locations for Barley

NAFTA Growing Zones Barley

Submitted Requested

Canada1 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 5
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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 HalauxifenMethylHalauxifenMethylHalauxifenMethylHalauxifenMethyl

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 D416127

Page 41 of 56

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

Compound HalauxifenMethylHalauxifenMethylHalauxifenMethylHalauxifenMethyl

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 D416127

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 Mexico2 Codex3

40 CFR 180.371

Plants: 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-

methoxyphenyl)-2-pyridinecarboxylate

NA NA NA

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

US Canada Mexico2 Codex3

Barley, grain 0.01

Barley, hay 0.01

Barley, straw 0.01

Wheat, forage 0.5

Wheat, grain 0.1

Wheat, hay 0.03

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 = 

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

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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

HalauxifenMethyl

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 (0.011)

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 with Fat PH: 0.5 (<0.001)

Rat <5% of the AD in excreta

Water ND - 97%

HalauxifenMethyl 

Glucose 

Conjugate

Turnip Tops: PH 26.4 (0.021)

Turnip Tops: PY 28.7 (0.024)

Rotational Crops - -

Ruminant - -

Poultry - -

Rat - -

Water - -

HalauxifenMethyl

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 (0.003)

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 D416127

Page 44 of 56

Wheat Straw: PY 1.8 (0.001)

Turnip Tops: PH 3.1 (0.002)

Turnip Tops: PY 3.5 (0.003)

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% - 33%

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 D416127

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: PY 5.9 (0.009)

Wheat Hay: PH 5.0 (0.012)

Wheat Hay: PY 4.8 (0.020)

Wheat Straw: PH 5.2 (0.010)

Wheat Straw: PY 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 (0.002)

Liver PH: 14.5 (0.007)

Liver PY: 8.3 (0.004)

Rat - -

Water - -

X11449757 Wheat Forage: PH 5.1 (0.010)

Wheat Forage: PY 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 D416127

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 dose 
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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Attachment 6: Proposed Metabolic Pathways and Environmental Degradation Scheme

6.a. Proposed Metabolic Pathway of Halauxifen-Methyl in Wheat
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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 D416127

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6.c. Proposed Metabolic Pathway of Halauxifen-Methyl in Goats
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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6.d. Proposed Metabolic Pathway of Halauxifen-Methyl in Hens
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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6.e. Proposed Metabolic Pathway of XDE-729 Acid in Rats

Cl F

O

H3C

N

NH2

Cl

O

OH

OH

Cl F

N

NH2

Cl

O

OH

HO

O

O

S

Cl F

O

N

NH2

Cl

O

OH

O

HO

HO

OH OH

O

O

Cl F

N

NH2

Cl

O

OH

OH

O

OH

HO

HO

O

Cl F

O

H3C

N

NH2

Cl

O

O

Peak C

Sulfate conjugate of O-demethyl-XDE-729

Peak E

O-demethyl-XDE-729

Peak F

XDE-729

Peak B

Glucuronide conjugate of O-demethyl-XDE-729

Peak H

Acyl-glucuronide conjugate of XDE-729
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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6.f. Proposed Halauxifen-Methyl Environmental Transformation Scheme

N

NH2

Cl

O

O

Cl

O

F

Halauxifen-methyl

XDE-729

N

NH2

Cl

O

OH

Cl

O

F

X11393729

N

NH2

Cl

O

O

Cl

HO

F

N

NH2

Cl

O

OH

Cl

HO

F

X11406790 X11449757

N

NH2

OH

O

O

Cl

O

F

Deg. 10

N

O

O

O

Cl

O

F

Deg. 11

N

O OH

O

OH

Cl

O

F

Deg. 9

N

NH2

O

O

Cl

O

F

X11861662

N

NH

OH

O

O

Cl

O

F

Deg.13

O

N

OH

Cl

O

OH

Deg. 5

O

N

O

Cl

O

F

Deg. 14

O

Cl

O

OH

Deg. 16
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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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

Halauxifenmethyl

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

Halauxifenmethyl

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 βconjugated glucose)

Metabolism: 

turnips

Halauxifenmethyl

N-glucuronic 

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)-pyridine2-carboxylic acid

Rat metabolism DER: XR-729 

Parent

Metabolism: 

wheat, turnips, 

ruminants, 

poultry, rats, 

drinking water

Env fate: 

hydrolysis, soil 

photolysis, 

anaerobic soil 

metabolism
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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Structures of Halauxifen-Methyl Metabolites and Degradates

Code Name Chemical Abstracts Name Structure Where Found

XDE-729 

Acid

glucose 

conjugate

[3,4,5-trihydroxy-6-

(hydroxymethyl)tetrahydropyran

-2-yl] 4-amino-3-chloro-6-(4-

chloro-2-fluoro-3-methoxyphenyl)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 

glucosemalonyl 

conjugate

See proposed metabolic profile for wheat

Metabolism: 

wheat

N

Cl

NH2

Cl

O

HO O

F
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

Page 55 of 56

Structures of Halauxifen-Methyl Metabolites and Degradates

Code Name Chemical Abstracts Name Structure Where Found

X11406790 

N- or Oglucuronic 

acid 

conjugate

6-[[3-chloro-6-(4-chloro-2-fluoro-3-

hydroxy-phenyl)-2-methoxycarbonyl-4-

pyridyl]amino]-3,4,5-trihydroxytetrahydropyran-2-carboxylic acid or

6-[3-(4-amino-5-chloro-6-

methoxycarbonyl-2-pyridyl)-6-chloro2-fluoro-phenoxy]-3,4,5-trihydroxytetrahydropyran-2-carboxylic acid

or

Metabolism: 

ruminants

X11449757 4-amino-3-chloro-6-(4-chloro-2-

fluoro-3-hydroxyphenyl)-pyridine2-carboxylic acid

Rat metabolism DER: O-demethylXR-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 rats

Metabolism: 

rats

X11449757 

Acyl 

Glucuronide 

Conjugate

Rat metabolism DER: acylglucuronide conjugate of Odemethyl-XR-729 See proposed metabolic profile for rats

Metabolism: 

rats

Degradate 1 Unknown

Unknown

Metabolism: 

drinking water

Env. fate: 

aqueous 

photolysis

N

F

HO

Cl

O

OH

Cl

NH2

O

O

S

O

N

F

Cl

NH2

Cl

OH

O

HO
Halauxifen-Methyl Summary of Analytical Chemistry and Residue Data DP Number D416127

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