Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 3 of 43 Executive Summary

Aminocyclopyrachlor [ 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyr imidinecarboxylic acid ] is a new herbicide belonging to the pyrimidine carboxylic acid chemical class. The mode of action is d y sregulation of gene products involved in auxin receptor activity, which interferes with normal shoot and root development to st op the growth of weeds. Aminocyclo p yr achlor is currently registered for non

- crop use for general control of broadleaf weed s and woody species on private, public, and military lands. Three forms of aminocyclopyrachlor are currently registered: the parent acid aminocyclopyrachlor ( DPX

- MAT28; PC code 288008), the potassium salt (PC Code 288010), and the methyl ester ( DPX

- KJM44; aminocyclopyr achlor

- methyl; PC code 288009). This petition (PP#0F7817) is the first food/feed use r equest for aminocyclopyrachlor.

Under PP#0F7817, DuPont Crop Protection has requested the establishment of tolerances for the herbicide aminocyclopyrachlor, to be determined by measuring only the sum of aminocyclopyrachlor and aminocyclopyrachlor methyl ester, methyl 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate, calculated as the stoichiometric equivalent of aminocyclopyrachlor in/on the following commodities:

Cattle, fat

................................ ................................ .. 0.0 7 ppm Cattle, liver

................................ ............................... 0.06 ppm Cattle, meat

................................ .............................. 0.02 ppm Cattle, meat byproducts, except liver

....................... 0.4 ppm Goat, fat

................................ ................................ .... 0.07 ppm Goat, liver

................................ ................................ 0.06 ppm Goat, meat

................................ ................................ 0.02 ppm Goat, meat byproducts, except liver

........................ 0.4 ppm Grass, forage

............................................... 65 ppm Grass, hay

................................................. 125 ppm Horse, fat

................................ ................................ .. 0.07 ppm Horse, liver

................................ ............................... 0.06 ppm Horse, meat

................................ .............................. 0.02 ppm Horse, meat byproduc ts, except liver

......................... . 0.4 ppm Milk

................................ ................................ .......... 0.03 ppm Sheep, fat

................................ ................................ .. 0.07 ppm Sheep, liver

................................ .............................. 0.06 ppm Sheep, meat

................................ .............................. 0.02 ppm Sheep, meat byproducts, except liver

.................. 0.4 ppm

In conjunction with the proposed tolerances, DuPont has submitted a request for amended registration of the 50% dry flowable ( i.e., water dispersible granule; W G) formulation of aminocyclopyrachlor (EPA Reg. No. 352

- 787), the 2 lb a.i. /gal soluble liquid (SL) formulation of the potassium salt ( K salt ; EPA Reg. No. 352

- 786 , equivalent to 2 lb ae/gal aminoc yclopyrachlor ), and the 80 % WG form u lation of aminocyclopyrachlor

- methyl (EPA Reg. No. 352

- 785 , equivalent to 75% ae aminocyclopyrachlor ) for use on pasture and rangeland grass es

. Aminocyclopyrachlor is proposed for up to two foliar applications to pastur e andAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 4 of 43 rangeland grasses at 0.038

- 0.172 lb ai/A/application for a maximum seasonal rate of 0.281 lb ai/A, with a 0

- day preharvest interval (PHI) for grass forage and hay.

The nature of the residue in grasses is adequately based on an acceptable grass met abolism study reflecting application of aminocyclopyrachlor

- methyl

. Aminocyclopyrachlor and aminocyclopyrachlor

- methyl were the major identified residues in grass. The data indicate that aminocyclopyrachlor

- methyl is rapidly metabolized (demethylated) in grass to form the free acid aminocyclopyrachlor , which is subsequently decarboxylated to form the metabolite IN

- LXT69. Photo

- induced simultaneous elimination of hydrogen chloride and pyrimidine ring contraction (occurring as a minor pathway) yields the i midazole

- nitrile metabolite, IN

- QGC48, which undergoes demethylation to form IN

- QFH57; IN

- QFH57 may also be formed through photolysis of aminocyclopyrachlor . An additional minor pathway involves pyrimidine ring opening proceeding through the postulated in termediate IN

- YY905, with subsequent oxidations to form the amide and carboxylic acid compounds, IN

- Q3007 and IN

- V0977, respectively. HED has concluded that t he residues of concern for tolerance enforcement and risk assessment in grass are aminocyclopyrac hlor and aminocyclopyrachlor

- methyl. Additional metabolism studies may be needed to support future uses on additional crops.

The nature of the residue in ruminants is adequately understood based on an acceptable goat metabolism study reflecting dosing wi th aminocyclopyrachlor

- methyl

. A minocyclopyrachlor was the only identified residue in goat milk and tissues. The data indicate that aminocyclopyrachlor

- methyl is rapidly metabolized in the goat and is eliminated as aminocyclopyrachlor primarily in the ex creta. HED has concluded that t he residues of concern for tolerance enforcement and risk assessment in livestock are aminocyclopyrachlor and aminocyclopyrachlor

- methyl. Because grass is not a significant feed stuff for poultry, a hen metabolism study is not required at this time; however, a hen metabolism study may be needed to support future uses on additional crops.

The petitioner has proposed high performance liquid chromatography method s with tandem mass spectrometry detection ( HP LC/MS/MS) for enforc ement of tolerances for aminocyclopyrachlor on grass commodities, DuPont

- 22582 SU1 RV2, and livestock commodities, DuPont

- 27162, Revision No. 1

. The method s adequately determine residues of aminocyclopyrachlor and amin o cyclopyrachlor

- methyl as well as the metabolites IN

- LXT69 and INQFH57 and IN

QGC48 (grass commodities only)
, in /on grass forage and hay
, milk, eggs, and bovine tissues

. The validated limit of quantitation (LOQ) is 0.01 ppm for each analyte. HED has conclude d that the plant and livestock me thod are a dequate for enforcement purposes

. HED has determined that laboratory tolerance method validation (TMV s ) are not needed for the pro p osed enforcement method s for plant and livestock commodities

. The proposed enforcement methods or earlier versions of the methods were used for data collection in the submitted storage stability, cattle feeding , and grass crop field trial studies.

Acceptable multiresidue methods test data have been submitted for aminocyclopyrachlor and aminocyclopyrachlor

- methyl. T he data indicate that multiresidue methods may be appropriate for determination of aminocyclopyrachlor

- methyl but are not suitable for determination of aminocyclopyrachlor or for determination of the two analytes together. The submitted data will be forwa rded to the U.S. Food and Drug Administration ( FDA ) for further evaluation.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 5 of 43 Adequate storage stability data have been submitted for residues of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl and metabolite IN

- LXT69 in grass and livestock commodities and for metabolites INQFH57 and IN

- QGC48 in grass commodities . No additional storage stability data are required to support the submitted grass crop field trial study or the cattle feeding study.

An acceptable cattle feeding study has been submitted reflecti ng dosing of lactating dairy cows with aminocyclopyrachlor

- methyl at 73.3, 160, 455, and 1595 ppm in the diet. Samples of milk, skim milk, cream
, and tissues were analyzed for residues of aminocyclopyrachlor, aminocyclopyrachlor

- methyl, and metabolite IN

- LXT69. The data indicate that tolerances are needed for milk and ruminant commodities. The data will support the following tolerances for combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl (expressed in parent equivalents): of 0.0 2 p pm for milk, and 0. 3 0 ppm for the meat byproducts, 0.0 5 ppm for the fat, and 0.02 ppm for the muscle of cattle, goat, horse, and sheep

. Adequate field trial data have been submitted reflecting application of products containing aminocyclopyrachlor

- methyl and aminocyclopyrachlor to grasses

. Samples of grass forage and hay were analyzed for residues of aminocyclopyrachlor, aminocyclopyrachlor

- methyl, and metabolite s IN

- LXT69 , INQFH57, and IN

- QGC48. The data indicate that the proposed tolerances are too low

. Based on these data and the OECD tolerance calculator, HED concludes that the following tolerances for combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl (expressed in parent equivalents) are appropriate: 80 ppm for grass forage and 2 00 ppm for grass hay.

An adequate confined rotational crop study has been submitted. The data indicate that the metabolism of aminocyclopyrachlor in rotated crops is similar to that in primary crops. HED has concluded that the residue s of concern fo r the tolerance expression in rotational crops are aminocyclopyrachlor and aminocyclopyrachlor

- methyl. Aminocyclopyrachlor, aminocyclopyrachlor

- methyl, and IN

- LXT69 were identified in rotational crop commodities. Because residues of aminocyclopyrachlor a ccumulated above 0.01 ppm in turnip tops and corn forage, stover, and grain at a 300

- day plantback interval (PBI), limited field rotational crop data are now required to support the proposed use on grasses. Pending submission of the required limited field rotational crop trials, the labels must be revised to prohibit rotation to any crop other than grasses following application of aminocyclopyrachlor or aminocyclopyrachlor

- methyl.

There are no established or proposed Codex or Canadian maximum residue limi ts (MRLs) for aminocyclopyrachlor in or on any food or feed crops ; therefore, there are no harmonization issues.

Regulatory Recommendations and Residue Chemistry DeficienciesAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 6 of 43 HED has examined the residue chemistry database for aminocyclopyrachlor . Pending submission of a revised Section B and a revised Section F (see requirements below)
, there are no residue chemistry issu es that would preclude granting conditional registration for the requested uses of a minocyclopyrachlor on pasture and rangeland grasses or establishment of tolerances for residues of aminocyclopyrachlor in/on the following commodities as follow :
Tolerances are established for residues of the herbicide aminocyclopyrachlor, including its

m etabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of aminocyclopyrachlor, 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylic acid, and aminocyclopyrachlor methyl ester, methyl 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate, calculated as the stoichiometric equivalent of aminocyclopyrachlor.

Cattle, fat

................................ ................................ .. 0.0 5 ppm Cattle, meat byproducts

................................ ........... 0. 3 0 ppm Cattle, meat

................................ .............................. 0.02 ppm Goat, fat

................................ ................................ .... 0.0 5 ppm Goat, meat byproducts

................................ ............. 0. 3 0 ppm Goat, meat

................................ ................................ 0.02 ppm Grass, forage

................................ .............................. . 80 ppm Grass, hay

.................................................. 200 ppm Horse, fat

................................ ................................ .. 0.0 5 ppm Horse, meat byproducts

................................ ........... 0. 3 0 ppm Horse, meat

................................ .............................. 0.02 ppm Milk

................................ ................................ .......... 0.0 2 ppm Sheep, fat

................................ ................................ .. 0.0 5 ppm Sheep, meat byproducts

................................ ........... 0. 3 0 ppm Sheep, meat

................................ .............................. 0.02 ppm

A human health risk assessment is forthcoming.

860.1200 Directions for Use Pending submission and review of the required limited field rotational crop trials, the labels must be revised to prohibit rotation to any crop other than gr asses following application of aminocyclopyrachlor or aminocyclopyrachlor

- methyl.

860.1550 Proposed Tolerances The proposed tolerance s for grass forage and hay must be increased to 80 and 200 ppm, respectively. The proposed tolerance for milk must be redu ced to 0. 02 ppm. The proposed tolerance s for liver and the meat byproducts, except liver
, for cattle, horse, goat, and sheep must be replaced with the recommended tolerances for meat byproducts, as specified in Table 9

.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 7 of 43 860.1650 Submittal of Analytical Reference Standards An analytical reference standard for aminocyclopyrachlor

- methyl must be supplied and supplies replenished as requested by the Repository.

HED recommends that conversion to unconditional registration for the requested uses may be c onsidered when the following minor deficiencies have been resolved.

860.1900 Field Accumulation in Rotational Crops A limited field accumulation in rotational crops study needs to be submitted.

Background

The chemical structure and nomenclature of amin ocyclopyrachlor, aminocyclopyrachlor

- methyl
, and the potassium salt are summarized in Table s 1 .1

- 1.3 , and the physicochemical properties of aminocyclopyrachlor and its methyl ester are summarized in Table 2

. The chemical names and structures of the residu es of concern are presented in Appendix I.

Table 1 .1 . Test Compound Nomenclature

- Aminocyclopyrachlor

Chemical Structure

Common Name Aminocyclopyrachlor (parent acid) Company Experimental Name DPX

- MAT28 IUPAC Name 6

- ami no

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylic acid
CAS Name 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylic acid CAS Registry Number 858956

- 08

- 8 End

- use product (EP) 50% WG ( DuPont MethodTM 50 SG; EPA Reg. No. 352

- 787 )

Table 1

. 2 Test Compound Nomenclature

- Aminocyclopyrachlor

- methyl (methyl ester)

Chemical Structure

Common Name Aminocyclopyrachlor

- methyl Company experimental Name DPX

- KJM44Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 8 of 43 Table 1

. 2 Test Compound Nomenclature

- Aminocyclopyrachlor

- methyl (methyl ester)
I UPAC Name methyl 6

- amino

- 5

- chloro

- 2

- cyclopropylpyrimidine

- 4

- carboxylate
CAS Name methyl 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate CAS Registry Number 858954

- 83

- 3

End

- use product (EP) 80% WG ( DuPont DPX

- KJM44 80XP; EPA Reg. No. 352

- 785 ; equi valent to 75% ae aminocyclopyrachlor )

Table 1.3. Test Compound Nomenclature

- Aminocyclopyrachlor (potassium salt)

Chemical Structure

Empirical Formula C 8 H 7 ClKN 3 O 2 Common Name Aminocyclopyrachlor potassium salt Company Experimental Name DPX

- MAT28 potassium salt
IUPAC Name potassium 6

- amino

- 5

- chloro

- 2

- cyclopropylpyrimidine

- 4

- carboxylate
CAS Name potassium 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate CAS Registry Number 858956

- 35

- 1

End

- use product (EP) 2 lb/g al SL (DuPont MethodTM 240 SL; EPA Reg. No. 352

- 786 ; equivalent to 2 lb ae/gal aminocyclopyrachlor )

Table 2. Physiochemical Properties of Aminocyclopyrachlor
Parameter Value Reference Aminocyclopyrachlor (DPX

- MAT28) Melting point 140.8oC DP# 369057, J. Ryman et al., 3/17/10 pH (20.1°C) 3.34 Density (20°C) 1.34 g/mL Water solubility (20°C) 3.13 g/L (pH 4) 4.20 g/L (pH 7) 3.87 g/L (pH 9) Vapor pressure 6.92 x 10 - 6 Pa (20 °C) 4.91 x 10 - 6 Pa (25 °C)Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 9 of 43 Table 2. Physiochemical Properties of Aminocyclopyrachlor
Parameter Value Reference Dissociation constant (20°C) 4.65 Octan ol/water partition coefficient (log 10 ) at 20°C - 1.01 (pH 4)

- 2.48 (pH 7) 1.07 (mili

- Q water) UV/visible absorption spectrum pH/nm 1.8/220 7.0/285, 240, 210 10.5/280, 240, 210 Aminocyclopyrachlor

- methyl (DPX

- KJM44) Melting point 148.9oC DP# 369057, J. Ryman et al., 3/17/10 pH (20.1°C) 6.16 Density (20°C) 1.44 g/mL Water solubility (20°C) 0.354 g/L Vapor pressure 4.19 x10 - 4 Pa (20°C) 4.45 x10 - 4 Pa (25°C) Dissociation constant (20°C) Not applicable Octanol/water partition coefficient (log 10 ) at 20°C 1.87

UV/visible a bsorption spectrum pH/nm 1.8/300, 220 7.0/300, 235, 205 10.5/285, 235

860.1200 Directions for Use

DuPont has submitted draft amended label s for the 50% WG formulation (EPA Reg. No. 352

- 787 ) , the 2 lb/gal SL formulation (EPA R eg. No. 352

- 786) of the K salt , and the 80% WG formulation (EPA Reg. No. 352

- 786) of aminocyclopyrachlor

- methyl . A summary of the proposed use pattern is presented in Table 3.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 10 of 43 Table 3. Summary of Directions for Use of Aminocyclopyrachlor

.
Applic. Timi ng, Type, and Equip. 1 Formulation

[EPA Reg. No.] Applic.

Rate 2 (lb ai/A) Max. No. Applic. per Season 2 Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Pasture (including grass grown for hay) and Rangeland Grass es

Foliar, B r oadcast
, Ground (min. 10 gal/A) or aerial (min. 2 gal/A ) 50% WG [ 352

- 787 ]

2 lb/gal SL of the K salt 3 [352

- 78 6 ]

80% WG of aminocyclopyrachlor

methyl 4 [352

- 785] 0.038

-

0.172 2 0.281 0 (forage and hay) Apply to new plantings when the majority of grasses a re in the 3

- to 4

- leaf stage or to perennial native grasses and pasture grasses established for at least one growing season

. A 30

- day treatment interval is specified. Use of a spray adjuvant (nonionic surfactant or crop oil concentrate) is specified

. Mi nimum spray volume of 10 gal/A for ground applications and 2 gal/A for aerial applications.

1 Do not apply through any type of irrigation system ; a 12

- hour reentry interval is specified

. 2 Rates expressed in terms of the aminocyclopyrachlor ai. Based o n calculations, individual maximum application rates are 0.166 lb ai/A for the 50% WG, 0.172 lb ai/A for the 2 lb/gal K SL , and 0.164 lb ai/A for the 80% WG formulation. 3 Equivalent to 2 lb ae/gal aminocyclopyrachlor.
4 Equivalent to 75% ae/gal aminocy clopyrachlor.
The labels state that a nonionic surfactant (NIS) is the preferred adjuvant, to be included at 0.06

- 0.50% v/v ; crop oil concentrates (COCs), including petroleum or modified seed oil (MSO) may be used at up to 0.5% v/v for MSOs or at 1

- 2% v/v for all others

. The products may be tank mixed with other herbicides, insecticides, and fungicides that are registered for the same use sites, methods of application, and timings. When tank mixing, the most restrictive label limitations of the products being used are to be followed; use of a spray adjuvant is specified for postemergence applications.

The following rotational crop restrictions are speci fi ed: a 4

- month PBI is specified for grasses (over

- seeding or renovation ); and a 1

- year PBI is specifi ed for all other crops. Forage legumes may be seeded after a soil bioassay has been conducted verifying that the level of aminocyclopyrachlor in the soil will not adversely e ffect the new crop.

Conclusions . The submitted use directions are sufficient t o allow for evaluation of the available residue data relative to the proposed use

. The submitted field trial data for grass reflect the maximum proposed use rate and the minimum PHI and support the use of spray adjuvants for applications to grasses.

The results of the confined rotational crop study indicate that limited rotational crop studies are required to establish PBIs an d /or tolerances for rotated crops. Pending submission of the required limited field rotational crop trials, the labels must be re vised to prohibit rotation to anyAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 11 of 43 crop other than grasses following application of aminocyclopyrachlor or aminocyclopyrachlor

methyl.

860.1300 Nature of the Residue

- Plants

DER Reference: 48333617.DER
E. I. du Pont de Nemours and Company has submitted a study investigating the metabolism of [2

- pyrimidinyl

14 C]aminocyclopyrachlor

- methyl (specific activity 1.64 MBq/mg) following a single foliar application to grass. Aminocyclopyrachlor

- methyl (DPX

- KJM44) is the methyl ester of aminocyclopyrachlor (DPX

- M AT28). The radiolabeled test substance was formulated as a 25% wettable powder (WP) and applied at a nominal rate of 0.333 lb ai/A (373 g ai/ha), equivalent to 0.312 lb ae/A (350 g ae/ha) aminocyclopyrachlor

. The application rate corresponds to 1.1x the maximum seasonal application rate for grass. Grass foliage samples were harvested immediately following application (0 days), and 3, 7, 14, 30, and 60 days after application (DAA), and were subjected to an acetonitrile (ACN) surface wash prior to storage. The in

- life and analytical phases of the study were conducted by Charles River Laboratories (Tranent, Edinburgh, UK).

Total radioactive residues (TRR) in grass were determined by summing radioactivity in surface washes, extracts, and nonextractable resi dues. TRR were 15.6, 15.4, 12.0, 5.94, 4.08, and 2.45 ppm in grass foliage harvested 0, 3, 7, 14, 30, and 60 DAA.

The TRR removed by the ACN surface wash declined from 13% TRR (2.03 ppm) at 0 DAA to 1.2% TRR (0.030 ppm) at 60 DAA. Extraction with ACN:fo rmic acid (8:2, v:v) released the majority of radioactivity from all but the 60

- DAA grass samples: extractable residues decreased from 76.6% TRR (12.0 ppm) at 0 DAA to 35.4% TRR (0.866 ppm) at 60 DAA. Subsequent extraction with ACN:formic acid (1:1, v:v) removed 8.3

- 12.0% TRR (1.28

- 0.715 ppm).

Nonextractable residues remaining following extraction increased with harvest interval, from 1.8% TRR (0.280 ppm) at 0 DAA to 51.7% TRR (1.27 ppm) at 60 DAA. The 0, 7, and 60 DAA nonextractable residues were su bjected to enzyme, base, and acid hydrolysis. Enzyme hydrolysis with α

- amylase ( 50 o C for 72 hours ) followed by a mixture of amyloglucosidase and cellulase ( 50 o C for 48 hours ) released, respectively, 0.7% and 0.3% TRR from the 0

- DAA sample, 1.5% and 1.0% TRR from the 7

- DAA sample, and 14.0% and 6.3% TRR from the 60

- DAA sample. Base (0.1 N NaOH ; 60 o C for 6 hours ) and acid (1 M HCl ; 60 o C for 6 hours ) hydrolysis each released 0.1% TRR from the 0

- DAA sample and 0.4% TRR from the 7

- DAA sample, and released 4.8% and 3.4% TRR, respectively, from 60

- DAA sample. The nonextractable residues remaining following extraction and hydrolysis accounted for 0.6% TRR (0.102 ppm) in 0

- DAA, 4.7% TRR (0.553 ppm) in 7

- DAA, and 23.4% TRR (0.572 ppm) in 60

- DAA samples.

The se procedures adequately extracted the majority of residues from grass collected at all harvest intervals with the exception of 60 DAA. With respect to the 60

- DAA sample, HED notes that 20% TRR was attributed to loss during analysis associated primarily w ith solid

- phase extraction (SPE) cleanup; therefore, further characterization procedures (e.g., strong acid or base hydrolysis) are unlikely to yield further elucidation of the metabolite profile. Extraction resultsAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 12 of 43 were normalized; therefore, accountabil ities were 100%. Residues were initially identified and quantitated by high performance liquid chromatograph y (HPLC); identification of aminocyclopyrachlor

- methyl and major metabolites was confirmed by liquid chromatography/mass spectroscopy (LC/MS).

S amples were stored frozen for up to 4.5 months prior to completion of initial analysis. A 60

- DAA sample was re

- extracted and analyzed at the end of the study following storage at

- 20 °C for 13 months to confirm the stability of the metabolite profile.

Am inocyclopyrachlor

- methyl was identified in grass from all harvest intervals; residues declined from 24.7% TRR (3.86 ppm) at 0 DAA to 8.6% TRR (0.211 ppm) at 60 DAA. aminocyclopyrachlor was the major identified residue in grass samples at all harvest inter vals, accounting for 32.9

- 67.7% TRR (0.805

- 10.5 ppm). Several minor metabolites were identified, including IN

- LXT69, IN

- QFH57, IN

- QGC48, IN

- Q3007, and IN

- V0977. IN

- LXT69 was identified at all sampling intervals, accounting for 4.2

- 6.1% TRR (0.138

- 0.769 ppm); the remaining metabolites were each present at ≤ 4.1% TRR.

Radiovalidation data were submitted for the extraction procedure of the proposed residue analyt ical enforcement method, DuPont

- 2 2582 and are discussed under 860.1340 Residue Analytical Metho ds

. Based on the results of the study, the petitioner concluded that aminocyclopyrachlor

- methyl is rapidly metabolized (demethylated) in grass to form the free acid aminocyclopyrachlor , which is subsequently decarboxylated to form IN

- LXT69. Photo

- indu ced simultaneous elimination of hydrogen chloride and pyrimidine ring contraction (occurring as a minor pathway) yields the imidazole

- nitrile metabolite, IN

- QGC48, which undergoes demethylation to form IN

- QFH57; IN

- QFH57 may also be formed through photolys is of aminocyclopyrachlor . An additional minor pathway involves pyrimidine ring opening proceeding through the postulated intermediate IN

YY905, with subsequent oxidations to form the amide and carboxylic acid compounds, IN

Q3007 and IN

- V0977, respectivel y. Chemical structures are shown in Appendix 1.

Conclusions

. The submitted grass metabolism study is adequate to satisfy data requirements. Based on the submitted data, HED concludes that the nature of the residue in grass is adequately understood for purposes of this petition. The residues of concern for tolerance enforcement and risk assessment are aminocyclopyrachlor and aminocyclopyrachlor

- methyl (expressed in parent equivalents)

. Additional metabolism studies may be needed to support future uses on additional crops.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 13 of 43 860.1300 Nature of the Residue

- Livestock

DER Reference: 48333618.DER

Ruminants

E. I. du Pont de Nemours and Company has submitted a study investigating the metabolism of [2

- pyrimidinyl

14 C]aminocyclopyrachlor

- methyl (DPX

- KJM44) in the lactating goat (specific activity 1.64 Bq/mg). The test substance was administered orally twice daily via gelatin capsule to one goat at a nominal 75 ppm in the diet for 5 consecutive days. Based on feed consumption, actual mean dose level was 91 ppm (parent acid equivalents) ( 1 x the dietary burden to cattle)

. Milk was collected twice daily throughout the study, before each dosing; tissues, including muscle (composite of loin, hind, and fore quarter), fat (omental, renal, and subcutaneous), liver, and kidney were collected at sacrifice, approximately 6 hours after the final dose. The in

- life and analytical phases of the study were conducted by Charles River Laboratories (Edinburgh, UK).

Following oral dosing at 97.3 ppm for 5 consecutive d ays, TRR were 0.015

- 0.031 ppm in milk, 0.299 ppm in liver, 1.673 ppm in kidney, 0.042 ppm in muscle, 0.01 ppm in omental fat, 0.016 ppm in renal fat, and 0.026 ppm in subcutaneous fat. Centrifugation of milk into skim milk and cream demonstrated that the majority of radioactive residues were present in the cream fraction. Radioactive concentrations in cream and skim milk were 0.118 and 0.016 ppm, respectively. Radioactivity was highest in kidney and lowest in fat. Radioactivity in milk appeared to plate au by Day 3. Most of the administered dose was excreted (~77%), with 20.02% in the feces, 54.07% in urine, and 3.14% in cage wash.

Extraction with 0.1% formic acid in ACN/water (tissues) or acetone (milk) released the majority of the radioactivity from a ll goat matrices, except omental fat: 86.7% TRR from liver, 98.3% TRR from kidney, 87.5% TRR from muscle, 80.5% TRR from milk, 83.8% TRR from renal fat, and 80.7% TRR from subcutaneous fat. Only 47.5% TRR was released in omental fat. Initial extraction of cream with hexane and acetone released 11.36% TRR in the acetone fraction and 84.96% TRR in the hexane fraction. The liver and kidney samples required SPE clean

- up prior to HPLC analysis to provide reproducible chromatographic profiles. Efforts to imp rove low recoveries resulting from SPE clean

- up impaired the quality of the chromatography, resulting in a significant loss of radioactive residues in the extracts; residues in the extracts after SPE cleanup were 57.40% TRR in liver and 55.26% TRR in kidne y. Nonextractable residues were not investigated further in muscle, milk, renal fat, subcutaneous fat, or omental fat; remaining nonextractable residues were 12.5% TRR (0.005 ppm), 19.5% TRR (0.004 ppm), 16.2% TRR (0.003 ppm), 19.3% TRR (0.005 ppm), and 5 2.6% TRR (0.005 ppm), respectively. Nonextractable residues of liver and kidney were subjected to sequential pepsin and protease enzyme hydrolysis which released 10.1% TRR and 1.5% TRR in liver, respectively, and 0.9% TRR and 0.12% TRR in kidney, respecti vely. Nonextractable residues remaining were 1.7% TRR (0.006 ppm) in liver and 0.68% TRR (0.011 ppm) in kidney. These procedures adequately extracted the majority of the residues from goat matrices. Results were normalized, thus accountabilities were 10 0% in all goat matrices.

Residues were initially identified and quantitated by HPLC. Identification of the parent acid, aminocyclopyrachlor, was confirmed in liver and kidney extracts prior to SPE clean

- up by TLCAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 14 of 43 co

- chromatography and in kidney extracts after SPE clean

- up by LC/MS/MS. Liver, kidney, muscle, and fat (renal and subcutaneous) were stored frozen for a maximum of 3.3 months prior to HPLC analysis. Omental fat and milk samples were initially extracted within 2.1 months of sample collection an d analyzed within 8.4 months of sample collection; milk was subsequently

re

- extracted and analyzed within 10.7 months of sample collection. The petitioner demonstrated that the metabolic profile in liver and kidney is relatively stable for 11 months. No additional storage stability data are required for omental fat because the TRR level was below the threshold concentration requiring meta bolite identification. Storage stability data for liver will be translated to milk.

Aminocyclopyrachlor

- methyl was not detected in excreta, milk
, or any tissue. The parent acid, aminocyclopyrachlor, was the only compound identified and was found in all matrices. It was the single radiolabeled component detected in liver (65.7% TRR; 0.197 ppm), kidney (55.3% TRR; 0.925 p pm), omental fat (47.5% TRR; 0.005 ppm), renal fat (83.8% TRR; 0.013 ppm), and subcutaneous fat (80.7% TRR; 0.021 ppm). Aminocyclopyrachlor was detected in muscle at 43.3% TRR (0.018 ppm) along with two unknowns (14.4

- 18.3% TRR; 0.006

- 0.008 ppm), and in milk at 15.9% TRR (0.004 ppm) along with three unknowns (7.4

- 29.5% TRR; 0.002

- 0.007 ppm). TLC analysis of liver and kidney extracts prior to SPE clean

- up (86.7% TRR and 98.3% TRR, respectively) confirmed that aminocyclopyrachlor was the only compound pres ent in these samples.

Based on the study results, the petitioner concluded that aminocyclopyrachlor

- methyl is rapidly metabolized in the goat and is eliminated as aminocyclopyrachlor primarily in the excreta. Chemical structures are shown in Appendix 1.

Conclusions

. The submitted goat metabolism study is adequate to satisfy data requirements

. Based on the submitted data, HED concludes that the nature of the residue in livestock is adequately understood for purposes of this petition . The residues of c oncern for tolerance enforcement and risk assessment are aminocyclopyrachlor and aminocyclopyrachlor

- methyl (expressed in parent equivalents)

. Because grass is not a significant feed stuff for poultry, a hen metabolism study is not required at this time ; however, a hen metabolism study may be needed to support future uses on additional crops.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 15 of 43 860.1340 Residue Analytical Methods

DER References: 48333620.DER (Plant method; includes review of MRIDs 48333617, 48333621, 48333625, and 48333626) 48333622.DER (Livestock method; includes review of MRIDs 48333623 and 48333627)

Plant Method

Enforcement method: DuPont has submitted an LC/MS/MS method , DuPont

- 22582 and revision DuPont

- 22582 SU1 RV2, for the determination of a minocyclopyrachlor (DPX

- MAT28), aminocyclopyrachlor

- methyl (DPX

- KJM44), and metabolites IN

- LXT69, QFH57, and IN

QGC48 in/on grass forage and hay. DuPont is proposing the revised method as an enforcement method, and has submitted method descriptions, metho d validation data, radiovalidation data, and ILVs of the method. The LC/MS/MS methods were used for data collection in the storage stability and crop field trial studies reviewed under PP#0F7817 (this petition)

. The method submissions include: (1) a description and validation data for the original method (DuPont

- 22582; MRID 48333620), which determine s residues of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 only; (2) a description and validation data for the revised version of the met hod (Supplement No. 1, Revision Nos. 1 and 2; DuPont

- 22582 SU1 RV2; MRID 48333621) which includes analysis for metabolites IN

- QFH57 and IN

- QGC48 and incorporates changes to the method resulting from the ILV studies; (3) two ILV studies (MRIDs 48333625 and 48333626); and (4) radiovalidation conducted in conjunction with the grass metabolism study (MRID 48333617). Except as noted, the method addressed and described hereafter is DuPont

- 22582 SU1 RV2.

Briefly, samples are soaked in 0.15 M ammonium acetate, then extracted with ACN and centrifuged. The supernatant is reserved, and the sample is extracted with ACN:0.15 M ammonium acetate (70:30, v:v) and centrifuged. The supernatants are combined, 0.1 N HCl is added, and the extract is diluted with water. F or analysis of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , IN

- LXT69, and IN

- QGC48, the extract is concentrated, then diluted with 0.5% formic acid and purified through a strong anion exchange (SAX) SPE cartridge after which it is transferred to a mixe d

- mode (cation exchange and reverse

- phase; MCX) SPE cartridge. Residues are eluted with 75 mM ammonium hydroxide in methanol, and the eluate is combined with 0.2% formic acid, concentrated, and diluted with 0.01% formic acid, then filtered for analysis by LC/MS/MS. For analysis of IN

- QFH57, the extract is concentrated, then diluted with 0.01% formic acid and purified through a SAX SPE cartridge. Residues are eluted with 1% formic acid in methanol, and the eluate is combined with 0.0 1% formic acid, concentrated, and diluted with 0.01% formic acid, then filtered for analysis by LC/MS/MS. Two transition ions are monitored for each analyte. An HPLC using a Phenomenex Phenyl

- Hexyl analytical column and a gradient mobile phase of 0.1% fo rmic acid in water and methanol; and an Applied Biosystems API

- 5000 Triple Quadrupole with electrospray interface (ESI) positive (negative for IN

- QHF57) mode Multiple Reaction Monitoring (MRM).Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 16 of 43 The transition ions monitored are: Aminocyclopyrachlor

- met hyl : 228→68 m/z and 228→168 m/z A minocyclopyrachlor : 214→68 m/z and 214→101 m/z IN

- LXT69: 170→76 m/z and 170→103 m/z IN

- QFH57: 176→132 m/z and 176→105 m/z IN

- QGC48: 192→178 m/z and 192→132 m/z

Based on the lowest level of method validation, the LOQ is 0. 01 ppm for all analytes in all matrices. The reported limits of detection (LODs) (based on 3X the baseline noise in a control extract) are 0.002 ppm for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- QGC48, 0.003 ppm for IN

- QFH57, and 0.0003 ppm for IN

- LXT69 in/on grass forage; and 0.002 ppm for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- QGC48, 0.003 ppm for IN

- QFH57, and 0.0005 ppm for IN

- LXT69 in/on grass hay.

Acceptable method validation recoveries for DuPont

- 22582 and DuPont

- 2258 2 SU1 RV2 were obtained for all analytes from samples of grass forage and hay fortified at 0.01 and 0.10 ppm. M ean recoveries and coefficients of variation (CV s ) were 73

- 95% (0

- 8.9%) for DuPont

- 22582 and 71

- 93% (1.0

- 17%) for DuPont

- 22582 SU1 RV2. The val idation data include results of an analytical laboratory method tryout (MTO) conducted by ABC Laboratories. Acceptable method validation recoveries were obtained for all analytes from samples of grass forage and hay. The fortification levels used in meth od validation
, in conjunction with concurrent method validation
, are adequate to bracket expected residue levels in/on grass forage and hay.

Two ILV studies were also conducted using samples of grass hay fortified at 0.010 and 0.10 ppm for all analytes. The first ILV study was conducted on DuPont

- 22582 Supplement 1 by MPI Research, Inc. (State College, PA), and the second ILV study was conducted on DuPont

- 22582 Supplement 1 (Revision 1) by ABC Laboratories (Columbia, MO). The first ILV study was

unsucce ssful for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , IN

- LXT69, and IN

QGC48; only IN

- QFH57 was successfully recovered in the second of three trials, with mean recoveries of 97

- 111%. The second ILV, which reflected an alternative simplified purificat ion procedure that used SAX SPE only, was successful for recovery of aminocyclopyrachlor

- methyl
, aminocyclopyrachlor , IN

- LXT69, and IN

- QGC48. The petitioner indicated that additional results from the second ILV reflecting the SPE/MCX purification procedur es described above will be reported separately (in Study No. 65869a/D

- 30574, Supplement 1).

For the second ILV study to be acceptable, the petitioner must confirm that the laboratory personnel involved in the ILV were unfamiliar with the method. OPPTS 86 0.1340 requires that the personnel chosen to conduct the ILV trials must be unfamiliar with the method, both in its development and in its subsequent use in analyzing field samples. Because ABC Laboratories was the analytical laboratory for the storage st ability and crop field trials reviewed under PP# 0F7817 , performed an analytical laboratory MTO on DuPont

- 22582, and was responsible for the development of the alternative SAX SPE cleanup procedure that was validated in the second ILV study, it appears ther e may be a potential conflict with the guideline requirements for ILV. The registrant has since submitted information stating the personnel involved in the ILV were not involved in method development (XXXXXXXX) therefore, this deficiency is resolved.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 17 of 43 Du Pont submitted radiovalidation data with the grass metabolism study to evaluate the efficiency of the extraction methodology presented in DuPont

- 22582 for extracting aminocyclopyrachlor and IN

- QFH57 from field

- grown grass. Aminocyclopyrachlor

- methyl , IN

- L XT69, and IN

QGC48 were also evaluated; however, resolution using the residue analytical method was inadequate to allow individual quantification using HPLC methodology. The extraction efficiencies were determined to be 108%, 126%, and 73%, respectively, for aminocyclopyrachlor , IN

- QFH57, and components with a similar retention time to IN

- LXT69, IN

- QGC48, and aminocyclopyrachlor

– methyl in 14 C

- labeled grass.

A confirmatory method was not included; however none is required because the LC/MS/MS method moni tors two transition ions for each analyte.

Data collection methods : The proposed enforcement method, DuPont

- 22582 SU1 RV2, and earlier versions of the method, including DuPont

- 22582 and DuPont

- 22582, Supplement No. 1, were used for data collection in the storage stability and crop field trial studies reviewed under PP#0F7817. Original method DuPont

- 22582 included analysis for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69, and DuPont

- 22582, Supplement No. 1 added analysis for metabolites I N

- QFH57 and IN

- QGC48. The methods were adequately validated concurrently with the storage stability and crop field trial studies.

Livestock Method

DuPont has submitted a n LC/MS/MS method , DuPont

- 25836 and a revised version of the method, DuPont

- 27162, Revision No. 1, for the determination of aminocyclopyrachlor (DPX

MAT28), aminocyclopyrachlor

- methyl ( DPX

- KJM44 ), and metabolite IN

- LXT69 in bovine muscle, liver, kidney, fat, milk, and feces. DuPont is proposing the revised method a s an enforcement method, and has submitted method descriptions, method validation data, and ILV of the method. The LC/MS/MS method was used for data collection in the cattle feeding study reviewed under PP#0F7817

. The method submissions include: (1) a description and validation data for the original method (DuPont

- 25836; MRID 48333623); (2) a description and validation data for the revised version of the method (DuPont

- 27162, Revision No. 1; MRID 48333622) which includes minor modifications to the met hod and incorporates changes to the method resulting from the ILV study; and (3) an ILV (MRIDs 48333627) conducted on DuPont

- 27162. Except as noted, the method addressed and described hereafter is DuPont

- 27162, Revision No. 1. We note that, although the procedures of methods DuPont

- 25836 and DuPont

- 27162 are essentially identical, the method description for DuPont

- 27162 establishes separate sections for analysis of milk (Method No. 1474A), bovine muscle and feces (Method No. 1474B), and bovine liver, kidn ey, and fat (Method No. 1474C). In addition, the original method provides instructions for analysis of skim milk, cream, whole eggs
, and fish, while the revised method does not include these matrices.

Briefly, milk samples are extracted twice with ACN :0. 1% formic acid (90:10, v:v) and centrifuged. The combined extracts are diluted with extraction solvent, then adjusted to volume with 0.01% formic acid for analysis by LC/MS/MS. Liver, kidney, fat, muscle, and fecesAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 18 of 43 samples are extracted sequentially with ACN:0.1% aqueous formic acid (at 90:10, v:v; 70:30, v/v; and 50:50, v/v) and centrifuged. The combined extracts are diluted with 0.1% formic acid and concentrated. An aliquot of the concentrated extract of liver, kidney, and fat is diluted with 0.01% fo rmic acid for analysis by LC/MS/MS. An aliquot of the extract of muscles and feces is diluted with 0.2% aqueous formic acid and purified on a n MCX SPE cartridge. Residues are eluted with 75 mM ammonium hydroxide in methanol, and the eluate is combined wi th 0.2% formic acid, concentrated, and combined with 0.01% formic acid for analysis by LC/MS/MS

. Two ion transitions are monitored for each analyte. An HPLC using a Phenomenex Luna Phenyl

- Hexyl analytical column and a gradient mobile phase of 0.01 M aque ous formic acid and methanol; and an Applied Biosystems API

- 4000 Triple Quadrupole with turbo ion spray interface in positive mode Multiple Reaction Monitoring (MRM) was used . The method notes that if background levels of AMINOCYCLOPYRACHLOR

- METHYL are fo und, this analyte may also be analyzed with an isocratic mobile phase of 0.01 M formic acid:methanol at 40:60 (v:v).

The transition ions monitored are: Aminocyclopyrachlor

- methyl : 228.1 →68.2 m/z and 228.1→100.9 m/z A minocyclopyrachlor : 214.2→68.1 m/z and 214.2→101.1 m/z IN

- LXT69: 170.1→76.1 m/z and 170.1→103.1 m/z

Based on the LLMV, the LOQ is 0.01 ppm for all analytes in all matrices. The reported LODs (based on 3X the baseline noise in a control extract) for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69, respectively, are 0.0065, 0.0021, and 0.0022 ppm in muscle; 0.0074, 0.00044, and 0.0010 ppm in liver; 0.0056, 0.0016, and 0.0014 ppm in kidney; 0.0056, 0.00059, and 0 .0010 ppm in fat; 0.0055, 0.00091, and 0.0028 ppm in milk; and 0.0039, 0.0012, and 0.0015 ppm in feces.

Acceptable method validation recoveries for method DuPont

- 25836 were obtained for all analytes from samples of bovine muscle, liver, kidney, fat, skim milk, whole milk, heavy cream, whole eggs, and fish fortified at 0.01 and 0.10 ppm. T he mean recoveries were 81

- 103% for aminocyclopyrachlor , 79

- 106% for aminocyclopyrachlor

- methyl , and 74

- 102% for IN

- LXT69
, with CV s <20% for each matrix tested. Acceptab le method validation recoveries for method DuPont

- 27162, Revision No. 1 were obtained for all analytes from samples of bovine muscle, liver, kidney, fat, milk, and feces fortified at 0.01 and 0.10 ppm. T he mean recoveries were 75

- 111% for aminocyclopyrach lor , 77

- 104% for aminocyclopyrachlor

- methyl , and 73

- 103% for IN

LXT69
, with CVs <20% for each matrix tested. The fortification levels used in method validation in conjunction with concurrent method validation are adequate to bracket expected residue level s in livestock tissues and milk.

An ILV study was also conducted on DuPont

- 27162 using samples of bovine liver, milk, and eggs fortified with aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 at 0.010 and 0.10 ppm. The first trial was success ful for all analytes in milk and eggs, with acceptable mean recoveries ranging from 92%

- 110% (CVs <20%). The first trial was also successful for IN

- LXT69 in bovine liver (mean recoveries 102

- 106%) but was unsuccessful for aminocyclopyrachlor and aminocycl opyrachlor

- methyl . Low recoveries for aminocyclopyrachlor

– methyl and high recoveries for aminocyclopyrachlor indicated thatAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 19 of 43 aminocyclopyrachlor

– methyl was converting to aminocyclopyrachlor during the analysis. The second trial for liver was successful for aminocyclopyrachlor and aminocyclopyrachlor

– methyl (mean recoveries 80

- 97%) when the performance validation set was separated into four smaller sub

- sets to minimize the observed degradation of aminocyclopyrachlor

- methyl

.
No radiovalidation data were submitted to support the submitted livestock analytical method ; however, no data are required because the extraction solvents use d in the goat metabolism study are the same as those used in the residue analytical method. Acceptable extraction efficiencies were indicated in the metabolism study; therefore, no additional data are required.

A confirmatory method was not included; however none is required because the LC/MS/MS method monitors two ion transition s for each analyte.

Data collection methods : A n earlier version of the proposed enforcement method, DuPont

27162
, was used for data collection in the storage stability and cattle feeding studies reviewed under PP#0F7817. The method included analysis for aminocyclopyrachlor
, aminocyclopyrachlor , and I N

- LXT69 in milk and bovine tissues. The method was adequately validated concurrently with the storage stability and crop field trial studies.

Conclusions

. The submitted residue analytical methods data are adequate to satisfy data requirements for the s ubject petition. HED has concluded that the livestock method is adequate for enforcement purposes, and that the grass method is adequate for enforcement purposes

. The Agency has considered the submitted data and has reviewed the analytical methods against the TMV (Tolerance Method Validation) checklist contained in ACB (Analytical Chemistry Branch/BEAD)’s SOP No. 019, Revision 1.0. HED has determined that TMVs are not needed for the proposed enforcement methods for plant and livestock commodities.

The analytical methods submitted under the subject action do not provide for conversion of residues of aminocyclopyrachlor

- methyl to stoichiometric equivalents of aminocyclopyrachlor and the residue data presented herein do not reflect correction to stoichiome tric equivalents. The conversion factor, based on molecular weights (MWs) of 213.6 for aminocyclopyrachlor and 227.6 for aminocyclopyrachlor

- methyl is 0.93849.

860.1360 Multiresidue Methods

DER References: 48333624.DER

DuPont has submitted multiresi due methods testing data for aminocyclopyrachlor (DPX

MAT28) and aminocyclopyrachlor

- methyl (DPX

- KJM44). The test substances were screened through multiresidue methods described in the U.S. FDA Pesticide Analytical Manual Volume I (PAM Vol. I)

. The study was conducted by Pyxant Labs Inc. (Colorado Springs, CO).

AMINOCYCLOPYRACHLOR was tested through Protocols A, B, and C; based on the results of these tests, it was not further tested through Protocols D, E, or F

. A minocyclopyrachlor

methyl was tested t hrough Protocols A, B (via methylation of aminocyclopyrachlor ), C, D, E and F. Neither aminocyclopyrachlor nor aminocyclopyrachlor

- methyl was tested under Protocol G because the compounds are not substituted ureas.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 20 of 43 The test substances were not found to be naturally fluorescent; therefore, further testing under Protocol A was not required.

Protocol B testing was conducted on aminocyclopyrachlor because it has an acid structure; methylation in Protocol B testing yielded the methyl ester, aminocyclopyrach lor

- methyl . Both test substances were found to be chromatographable in Protocol C testing; therefore, aminocyclopyrachlor was methylated according to Protocol B with observed conversion of 37.2% to the methyl ester (DPX

- KJM44). Acceptable recovery was ob tained through Florisil (93%), but recovery through gel permeation chromatography (GPC) was unacceptable (14.2%); therefore, no further testing was conducted under Protocol B.

In Protocol C testing aminocyclopyrachlor was chromatographable in Section 302, Level II testing, using module DG

- 5 with nitrogen

- phosphorus detection (NPD). A minocyclopyrachlor

methyl was chromatographable in Section 302, Level I testing, using module DG

- 5 (NPD). The results of Protocol C testing indicated that further testing of aminocyclopyrachlor

- methyl under Protocols D

- F was required.

Based on the results of Protocol C testing, aminocyclopyrachlor

- methyl was tested through Protocol D without cleanup. Testing under Protocol D, Section 302, E1, yielded complete recovery (109 %) of aminocyclopyrachlor

- methyl in skim milk fortified at 0.1 ppm and partial recovery (53%) in skim milk fortified at 0.5 ppm.

Testing of aminocyclopyrachlor

- methyl through Protocols E and F was suspended because recovery through Florisil was unaccepta ble.

These data indicate that Protocol D described in FDA PAM Vol. I may be applicable for determination of aminocyclopyrachlor

- methyl ; however, the FDA multiresidue methods are not appropriate for determining residues of aminocyclopyrachlor , or for the two compounds ( aminocyclopyrachlor

- methyl and aminocyclopyrachlor ) together.

Conclusions

. The submitted multiresidue methods test data for aminocyclopyrachlor and DPX

KLM44 are acceptable. The data indicate that multiresidue methods are not suitable fo r determination of aminocyclopyrachlor or for determination of the two analytes together . The submitted data will be forwarded to the U.S. FDA for further evaluation.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 21 of 43 860.1380 Storage Stability

DER References: 48333628.DER (Grass; includes re view of MRID 48333629)

48363401.DE2 (Milk, eggs, and bovine tissues)

Grass

DuPont has submitted the results of two storage stability studies with aminocyclopyrachlor (DPX

- MAT28), aminocyclopyrachlor

- methyl (DPX

- KJM44), and the metabolites, IN

- LXT69, IN

- QFH57, and IN

- QGC48 in grass forage and hay. Separate studies were submitted for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 (MRID 48333628), and for IN

- QFH57 and IN

- QGC48 (MRID 48333629). Samples of untreated g rass forage and hay we re fortified with aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 at 0.50 ppm each for forage and 1.0 ppm each for hay, and with IN

- QFH57 and IN

- QGC48 at 0.30 ppm each for both forage and hay. The fortified samples were stored frozen (

- 20 ° C ) and analyzed at target intervals of 0, 7, 14, 30, 60, 90, 150, 210, 300, 360, and 400

- 500 days. Both studies were conducted by ABC Laboratories, Inc. (Columbia, MO).

Grass forage and hay samples were analyzed for residues of aminocyclopyrachlor
, amin ocyclopyrachlor

- methyl , IN

- LXT69, IN

- QFH57, and IN

- QGC48 by LC/MS/MS using DuPont

- 22582 (for analysis of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , IN

- LXT69) and DuPont

- 22582 Supplement No.1 (for analysis of IN

- QFH57 and IN

- QGC48). The methods

are a cceptable for data collection based on adequate method validation data and concurrent method recovery data. The validated LOQ was 0.01 ppm in grass forage and hay.

The study results indicate that residues of aminocyclopyrachlor
, aminocyclopyrachlor

- meth yl
, and IN

- LXT69 are stable in/on grass forage and hay stored frozen (

- 20 °C) for up to 499

- 502 days (~16.5 months), and residues of IN

- QFH57 and IN

- QGC48 are stable in/on grass forage and hay stored frozen for up to 401

- 402 days (13.2 months).Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 22 of 43 Sample storage intervals and conditions

The storage durations and conditions of samples from the crop field trials and processing s tudies submitted to support th is petition are presented in Table 4

.

Table 4 . Summary of Storage Conditions and Durat ions o f Samples from Crop Field Trial Stud y Matrix Analyte s Storage Temperature (°C) Actual Storage Duration Interval of Demonstrated

Storage Stability Grass forage aminocyclopyrachlo

r , aminocyclopyrachlo

r

- methyl , IN

LXT69, INQFH57, and IN

- QGC48 - 20 3 7

- 400 days (1.2

- 13.2 months) 499

- 502 days (~16.5 months)

for aminocyclopyrachlor

methyl
, aminocyclopyrachlor and IN

- LXT69 and 401

- 402 days (13.2 months) for metabolites IN

- QFH57 and IN

- QGC48 Grass hay 41

- 408 days (1.3

- 13.4 months)

Conclusions . Accep table supporting storage stability data have been submitted for grass forage and hay. No additional storage stability data are required to support the submitted grass crop field trials.

Livestock Commodities

DuPont has submitted the results of a storage stability study with aminocyclopyrachlor (DPX

MAT28), aminocyclopyrachlor

- methyl ( DPX

- KJM44 ), and metabolite IN

- LXT69 in milk, eggs, and bovine tissues. The study was conducted concurrently with the cattle feeding study. Samples of homogenized bovine mu scle, liver, kidney, fat, milk, and eggs were fortified with aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 at 0.2 ppm. The fortified samples were placed in frozen storage at approximately

- 20 °C and analyzed at target intervals of 1 and 2 weeks, and 1, 2, 3, and 5 months; kidney was not analyzed at 5 months. In addition, extracts of liver and kidney were stored frozen at ~

- 20 °C and analyzed after storage intervals of 7 and 14 days. The study was conducted by Charles River Laboratories (T ranent, Edinburgh, Scotland)

Samples of milk, eggs, and tissues were analyzed for residues of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and metabolite IN

- LXT69 by a n LC/MS/MS method , DuPont

27162. Samples of liver and kidney fortified with aminoc yclopyrachlor

- methyl were analyzed for residues of both aminocyclopyrachlor

- methyl and aminocyclopyrachlor to investigate biotransformation. We note that the method description for DuPont

- 27162 establishes separate sections for analysis of milk (Method No . 1474A), bovine muscle and feces (Method No. 1474B), and bovine liver, kidney, and fat (Method No. 1474C). This method is acceptable for data collection based on adequate method validation and concurrent recovery data. Based on the LLMV, the LOQ for ami nocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 was 0.01 ppm in milk and tissue samples.

The study results indicate that residues of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl
, and IN

- LXT69 are stable in milk, eggs, and bovine muscle and fat stored frozen (~

- 20 °C) for up to 5 months, and that residues of aminocyclopyrachlor and IN

- LXT69 are stable in liver andAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 23 of 43 kidney for up to 5 and 3 months, respectively. aminocyclopyrachlor

- methyl was not stable in homogenized liver or kidney stored fr ozen for ≥1 week; however, the recovery of aminocyclopyrachlor from samples fortified with aminocyclopyrachlor

- methyl demonstrated the biotransformation of aminocyclopyrachlor

- methyl to aminocyclopyrachlor under frozen storage conditions. When recoveries for aminocyclopyrachlor

- methyl in stored samples were adjusted for biotransformation to aminocyclopyrachlor , corrected recoveries at all storage intervals were 92

- 98% for liver and 91

- 102% for kidney. All analytes were found to be stable in extracts of li ver and kidney stored frozen for up to 14 days.

Sample storage intervals and conditions

The storage durations and conditions of samples from the cattle feeding submitted to support this petition are presented in Table 5

.

Table 5 . Summary of Storage Conditions and Durations of Samples from the Cattle feeding Study Matrix Analyte Storage Temperature (°C) Actual Storage

Duration Interval of Demonstrated Storage Stability

Milk, skim milk, and cream aminocyclopyrachlor
,

aminocyclopyrachlor

methyl , and IN

- LXT69 - 20 2

- 65 days (0.1

- 2.1 months) Up to 146 days (4.8 months)

Muscle 12

- 44 days (0.4

- 1.5 months) Up to 138 days (4.5 months)

Fat 11

- 36 days (0.4

- 1.2 months) Up to 147 days (4.8 months)

Kidney 0 and 16

- 45 days (0 and 0.5

- 1.5 months) Up to 8 8 days (2.9 months) for

aminocyclopyrachlor and IN

LXT69. Residues of aminocyclopyrachlor

- methyl were unstable; however, biotransformation to aminocyclopyrachlor accounted for nearly all loss on storage. Liver 0 and 28

- 29 days Up to 147 days (4.8 month s) for aminocyclopyrachlor and IN

LXT69. Residues of aminocyclopyrachlor

- methyl were unstable; however, biotransformation to aminocyclopyrachlor accounted for nearly all loss on storage.

Conclusions

. Acceptable supporting storage stability data have be en submitted for milk and bovine tissues and hay. No additional storage stability data are required to support the submitted cattle feeding study.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 24 of 43 860.1400 Water, Fish, and Irrigated Crops
There are no proposed uses that are relevant to this guideline t opic.

860.1460 Food Handling
There are no proposed uses that are relevant to this guideline topic.

860.1480 Meat, Milk, Poultry, and Eggs

DER Reference: 48363401.DE 1

The livestock feedstuffs associated with PP# 0F7817 are grass forage and hay; these c ommodities are fed to beef and dairy cattle but are not fed to poultry or swine. The dietary burdens of aminocyclopyrachlor to cattle , based on reasonably balanced diets, are presented in Table 6

. The maximum reasonable dietary burden for cattle is 90 p pm.

Table 6

. Calculation of Dietary Burdens of Aminocyclopyrachlor Residues to Livestock.

Feedstuff Type 1 % Dry Matter 2 % Diet 2 Highest Average Field Trial (ppm) 4 Dietary Contribution (ppm) 3
Beef Cattle Grass hay R 88 15 117 19.9 CC not registered CC

-- 80

-- -- PC not registered PC

-- 5

-- -- TOTAL BURDEN

-- -- 100

-- 19.9 Dairy Cattle Grass forage R 25 45 50 90 CC not registered R

-- 45

-- -- PC not registered CC

-- 10

-- -- TOTAL BURDEN

-- -- 100

-- 90
1 R: Roughage; CC: Carbohydrate c oncentrate; PC: Protein concentrate. 2 OPPTS 860.1000 Table 1 Feedstuffs (June 2008). 3 Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle; contribution = ([tolerance] X % diet) for poultry and swine.
4 calculated as parent equiva lents

DuPont submitted a cattle feeding study with aminocylopyrachlor

- methyl (DPX

- KJM44). DPX

KJM44 is the methyl ester of aminocyclopyrachlor (DPX

- MAT28). In the study, four groups of dairy cows (3 cows/group; Groups 1

- 4) were dosed orally once a day w ith gelatin capsules containing aminocyclopyrachlor

- methyl ( DPX

- KJM44) at target doses of 1.8, 3.6, 10.8, and 36 mg/kg bw/day for 28 consecutive days. Based on the average feed consumption, the actual mean daily dose levels were equivalent to 73.3, 160, 45 5, and 1595 ppm in the diet (dry

- weight basis). The dosing levels correspond to ~0. 8 x, 1. 8 x, 5. 1 x, and 17.7 x the maximum reasonable dietary burden to cattle based on the proposed use on grass. An additional group of two cows (Group 5) was dosed at 1594 p pm for 28 days, to obtain depuration data. One control cow received capsules containing no aminocyclopyrachlor

- methyl (Group 6). The study was conducted by Charles River Laboratories (Tranent, Edinburgh, Scotland)Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 25 of 43 Cows were milked twice daily. For each cow, milk samples from the afternoon sampling were combined with milk samples from the next morning sampling to produce a daily sample. Samples of milk from Study Days

- 1, 1, 3, 5, 7, 10, 14, 17, 21, 24, and 28 from all dose groups were analyzed. Milk co llected on Days 14 and 21 was used for preparation of skim milk and cream samples. Milk samples were collected from the depuration group (Group 5) on Study Days 24 and 28 during the dosing period and on Depuration Days 1, 3, 5, 10, 14, and 16 post

dosing; only milk from Depuration Days 1, 3, 5, and 7 was analyzed. Skim milk and cream samples were prepared from milk collected on Depuration Days 3 and 10 post

- dosing. Control and treated cows except those in the depuration study were sacrificed ~22

- 24 hours after the final dose on Study Day 28. Samples of liver, kidney, fat (omental, renal, and subcutaneous), and muscle (loin, flank, and hind leg) were collected from each cow.

Milk and tissue samples were analyzed for residues of aminocyclopyrachlor

- methyl
, aminocyclopyrachlor , and metabolite IN

- LXT69 using an acceptable method, and the study is supported by adequate storage stability data. The method LOQ is 0.01 ppm for all analytes in milk and tissues.

All samples were stored frozen (approximately

- 20 o C) prior to extraction for analysis, except for samples of liver and kidney, which were generally processed fresh following sacrifice, due to storage stability issues for analysis of aminocyclopyrachlor

- methyl . The maximum storage durations from collectio n to extraction were 65 days for milk, 30 days for skim milk, 59 days for cream, 44 days for muscle, and 36 days for fat. Liver and kidney samples were generally extracted on the day of collection with the exception of selected repeat analysis samples. Ad equate storage stability data are available to support the storage conditions and durations of samples from the cattle feeding study.

Residues of aminocyclopyrachlor

- methyl and IN

- LXT69 were below the LOQ in all samples of milk, skim milk, cream, muscle , liver, kidney, and fat at all dose levels, except that quantifiable residues of 0.014 ppm aminocyclopyrachlor

- methyl were observed in liver from one cow at the 73.3

- ppm dose level. Quantifiable residues of aminocyclopyrachlor were observed in milk at th e 160

- , 455

- , and 1595

- ppm dose levels, although residues at the 160

- ppm dose level were generally near or below the LOQ on all sampling days. Quantifiable residues were observed in skim milk and cream beginning at the 160

- ppm dose level for skim milk and the 455

- ppm dose level for cream. In tissues, quantifiable residues of aminocyclopyrachlor were observed in liver, kidney, and fat at all dose levels and in muscle beginning at the 160

- and 1595

- ppm dose levels. In tissues, residues were highest in kidn ey, followed by fat, liver, and muscle.

Residues of aminocyclopyrachlor in milk appeared to reach a plateau by Day 7 for the 455

- ppm dose level but continued to increase at the 1595

- ppm dose level through study Day 28. We note that OCSPP 860.1480 speci fies that dosing should continue until residues plateau in milk if they have not done so in 28 days. Residues of aminocyclopyrachlor in milk (beginning from Day 7) were <0.01, <0.01

- 0.012, 0.016

- 0.026, and 0.040

- 0.10 ppm following dosing at 73.3, 16, 455, and 1595 ppm, and combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl were <0.02, <0.02

- <0.022, <0.026

- <0.036, and <0.05

- <0.11 ppm at the respective dose levels. There was no evidence of preferential transfer of residues to skim milk or cream; in general,Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 26 of 43 residues of aminocyclopyrachlor were slightly lower in cream at all dose levels with quantifiable residues. Residues in skim milk and cream (Study Days 14 and 21), respectively, were <0.01 (both), <0.01

- 0.013 and <0.01, 0.015

- 0.023 a nd <0.01

- 0.015, and 0.044

- 0.098 and 0.017

- 0.046 ppm at the 73.3

- , 16

- , 455

- , and 1595

- ppm dose levels; combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl in skim milk and cream, respectively, were <0.02 (both), <0.02

- <0.023 and <0.02, <0.025

- <0.033 and <0.02

- <0.025, and <0.054 and <0.108 and <0.027

- <0.056 ppm at the respective dose levels.

In kidney, residues of aminocyclopyrachlor were 0.092

- 0.17, 0.23

- 0.40, 0.20

- 0.54, and 0.68

- 1.4 ppm at the 73.3

- , 16

- , 455

- , and 1595

- ppm dose l evels , and combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl were <0.10

- <0.18, <0.24

- <0.41, <0.21

- <0.55, and <0.69

- <1.41 ppm. In fat, residues of aminocyclopyrachlor were <0.01

- 0.015, <0.01

- 0.040, 0.029

- 0.12, and 0.025

- 0.74 ppm at th e 73.3

- , 16

- , 455

- , and 1595

- ppm dose levels, and combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl were <0.02

- <0.025, <0.02

- <0.050, <0.039

- <0.13, and <0.035

- <0.75 ppm. In liver residues of aminocyclopyrachlor were <0.01

- 0.082, 0.020

- 0.064, 0.025

- 0.075, and 0.088

- 0.11 ppm at the 73.3

- , 16

- , 455

- , and 1595

- ppm dose levels, and combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl were <0.02

- <0.092, <0.03

- <0.074, <0.035

- <0.085, and <0.098

- <0.12 ppm. In muscle, residue s of aminocyclopyrachlor were <0.01, <0.01

- 0.012, <0.01, and 0.021

- 0.10 at the 73.3

- , 16

- , 455

- , and 1595

- ppm dose levels, and combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl were <0.02, <0.02

- 0.022, <0.02, and <0.031

- <0.11 ppm at t he respective dose levels.

Following cessation of dosing, residues in milk and tissues rapidly declined in the depuration group dosed at 1594 ppm for 28 days. Residues of aminocyclopyrachlor

- methyl and IN

- LXT69 were not detected above the LOQ (<0.01 ppm ) in any milk, skim milk, cream, or tissue samples. Residues of aminocyclopyrachlor were detected above the LOQ in one milk sample (0.017 ppm) on Depuration Day 1 and dropped below the LOQ by Depuration Day 3. Residues of aminocyclopyrachlor were detecte d above the LOQ in the muscle (0.019 ppm) and fat (0.030 ppm) of the cow sacrificed on Depuration day 15. For the cow sacrificed on Depuration day 17, the aminocyclopyrachlor residues were not detected in the muscle sample and increased to 0.056 ppm in th e fat sample.

Conclusions

. The submitted cattl e feeding study is acceptable for purposes of this petition. R esidues in milk did not reach a plateau at the highest dosing level (1595 ppm; 17.7 x) in the submitted study; however, because residues plateaued at 7 days at the 455

- ppm dose level ( 5. 1 x) and were generally near the LOQ at the 160

- ppm dose level (1. 8 x)
, HED believes the study is adequate to support the proposed use on grass only. Should other uses be proposed which result in an increase in the di etary burden for cattle, additional data may be required.

Samples were analyzed for aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69 using acceptable methods, and the study is supported by adequate storage stability data.

Based on the su bmitted data, HED has concluded that tolerances are needed for milk and the tissues of cattle, goat, horse, and sheep . Tolerances are not needed for milk fat because residues did not concentrate in cream.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 27 of 43 If the residues observed at various dosing levels are adjusted to a 1x feeding lev el for dairy cattle (see Table 7 ), maximum expected combined residues would be 0.02 ppm in milk, 0. 22 ppm in kidney, 0. 0 4 ppm in fat, 0.1 0 ppm in liver, and 0.0 2 ppm in muscle. Based on these data, tolerances are needed fo r meat b y products at 0. 3 0 ppm, for fat at 0.0 5 ppm, and for muscle at 0.02 ppm. The data indicate that a tolerance of 0.02 ppm (equivalent to the combined LOQs for aminocyclopyrachlor and aminocyclopyrachlor

- methyl ) would be appropriate for milk.

Table 7

. Summary of Data from Cattle Feeding Study with Aminocyclopyrachlor

- methyl.

Matrix Maximum combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl at each

dosing level 1 Residues adjusted to 1x feeding level for dairy cattle 2

73.3 160 45 5 1595 0. 8 x 1. 8 x 5. 1 x 1 8 x Milk (Days 7

- 28)

-- <0.022 <0.036 <0.11

-- 0.0 1 0.01 0.01 Skim milk

-- <0.023 <0.033 <0.11

-- 0.0 1 0.01 0.01 Cream

-- -- <0.025 <0.056

-- -- 0.01 0.01 Kidney <0.18 <0.41 <0.55 <1.41 0. 2 3 0. 2 3 0.1 1 0. 0 8
Fat <0.025 <0.050 <0.13 <0.75 0.0 3 0.0 3 0.0 3 0.0 4 Liver <0.092 <0.074 <0.085 <0.12 0.1 2 0.0 4 0.0 2 0.01 Muscle

-- -- -- <0.11

-- -- -- 0.01
1 The LOQ (0.01 ppm) was used for residues reported as ND or below the LOQ. For purposes of this calculation only, where maximum residu es were below the LOQ for both analytes, residues are indicated by

-- . 2 The dose rate factors calculated above based on actual dosing levels in calculations.
Because there are no poultry feedstuffs associated with the proposed use on grasses, data requi rements for a poultry feeding study are not relevant to this tolerance petition.

860.1500 Crop Field Trials

DER Reference: 48333630.DER

DuPont has submitted field trial data reflecting use of the potassium salt and methyl ester formulations on grass f

orage and hay in s upport of the proposed use of aminocyclopyrachlor on pasture and rangeland grasses

. The results from these field trials are discussed below and the residue data are summarized in Table 8

.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 28 of 43 Table 8

. Summary of Residue Data from Grass Crop Field Trials with the Methyl Ester and Potassium Salt Formulations of Aminocyclopyrachlor. Commodity TRT

Plot # 1 EP 2 Total Applic.

Rate 3

, lb ai or ae / A (g ai or ae /ha) PHI

(days) Residue Levels (ppm)

n Min. Max. H AFT 4 Median Mean Std. Dev. PASTURE AND RANGELAND GRASSES: proposed use = 0.281 lb ai/A total application rate, 0

- day PHI A minocyclopyrachlor

- methyl Grass, forage 1 80%

WG 0.274

- 0.299 (308

- 335) 0 44 7.7 47 47 22 23 10

2 2 lb/gal SL 0.275

- 0.285 (308

- 3 19) 0 12 0.014 0.15 0.15 0.031 0.050 0.047

3 80% WG 0.270

- 0.280 (303/314) 0 6 9.5 14 14 11 11 1.9
Grass, hay 1 80%

WG 0.274

- 0.299 (308

- 335) 0 44 13 108 103 35 38 20

2 2 lb/gal SL 0.275

- 0.285 (308

- 319) 0 12 0.061 0.89 0.73 0.15 0.24 0.25

3 80% WG 0.2 70

- 0.280 (303/314) 0 6 19 31 27 22 23 4.5

Aminocyclopyrachlor Grass, forage 1 80%

WG 0.274

- 0.299 (308

- 335) 0 44 0.76 14 13 2.2 3.2 2.7

2 2 lb/gal SL 0.275

- 0.285 (308

- 319) 0 12 12 41 39 20 23 8.9

3 80% WG 0.270

- 0.280 (303/314) 0 6 0.43 0.84 0.75 0.65 0.66 0.15
Grass, hay 1 80%

WG 0.274

- 0.299 (308

- 335) 0 44 2.4 80 79 16 18 16

2 2 lb/gal SL 0.275

- 0.285 (308

- 319) 0 12 29 58 49 41 41 8.3

3 80% WG 0.270

- 0.280 (303/314) 0 6 1.1 14 12 2.4 5.2 5.5

Combined residues of aminocyclopyrachlor + aminocyclopyra chlor

- methyl Grass, forage 1 80%

WG 0.274

- 0.299 (308

- 335) 0 44 8.7 54 53 25 26 12

2 2 lb/gal SL 0.275

- 0.285 (308

- 319) 0 12 12 41 39 20 23 8.9

3 80% WG 0.270

- 0.280 (303/314) 0 6 10 15 14 12 12 1.9
Grass, hay 1 80%

WG 0.274

- 0.299 (308

- 335) 0 44 28 133 129 50 57 27

2 2 lb/gal SL 0.275

- 0.285 (308

- 319) 0 12 29 59 49 41 41 8.5

3 80% WG 0.270

- 0.280 (303/314) 0 6 20 45 39 25 28 9.6

1 1= 80% WG formulation of aminocyclopyrachlor

- methyl , normal application volume; 2 = 2 lb/gal SL formulation of aminocycl opyrachlor ; and 3 = 80% WG formulation of aminocyclopyrachlor

- methyl , low application volume. 2 80% WG = WG formulation of aminocyclopyrachlor

- methyl and 2 lb/gal SL = SL formulation of aminocyclopyrachlor

.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 29 of 43 3 Rates reflect lb ae or ai/A aminocyclopyrach lor ; refer to the DER for 4833630 for comparison of rates with ai aminocyclopyrachlor

- methyl

. 4 HAFT = Highest Average Field Trial result.

DuPont has submitted field trial data for aminocyclopyrachlor (DPX

- MAT28), aminocyclopyrachlor

- methyl ( DPX

- KJM44), and metabolites IN

- LXT69, IN

- QFH57, and IN

QGC48 in/on grass forage and hay from pastures and rangelands in the U.S. and Canada. Twenty

- two field trials were conducted in the U.S. and Canada in Zones 1 (PA and PE, 3 trials), 2 (NJ, 1 trial), 5 (IA, MB, MO , NE, and ON, 6 trials), 6 (OK and TX, 3 trials), 7 (ND and SD, 2 trials), 8 (KS, 1 trial), and 14 (AB, MB, and SK, 6 trials) during the 2008 and 2009 growing

seasons.
Each field trial included one control plot and one treated plot. Treated plots recei ved a single foliar broadcast application of an 80% WG formulation of DPX

- KJM44 (methyl ester) at a target rate of 0.300 lb ai/A (336 g ai/ha), equivalent to 0.281 lb ae/A (315 g ae/ha) aminocyclopyrachlor . Actual application rates were 0.293

- 0.318 lb ai/ A (328

- 357 g ai/ha), equivalent to 0.274

- 0.299 lb ae/A (308

- 335 g ae/ha), with spray volumes of 10

- 30 gal/A. Additional side

- by

- side trials were conducted at selected sites as follow s . Six trials included a second treated plot which received a single fol iar broadcast application of a 2 lb/gal (240 g/L) SL formulation of aminocyclopyrachlor at a target rate of 0.281 lb ai/A (315 g ai/ha). Actual application rates were 0.275

- 0.285 lb ai/A (308

- 319 g ai/ha) with spray volumes of 10

- 30 gal/A. Three trials included a second treated plot which received a single foliar broadcast application of the 80% W G formulation of aminocyclopyrachlor

- methyl at a target rate of 0.300 lb ai/A (336 g ai/ha), equivalent to 0.281 lb ae/A (315 g ae/ha) DPX

- MAT 28, in a low volu me application. Actual application rates were 0.288

- 0.299 lb ai/A (323

- 335 g ai/ha), equivalent to 0.270

- 0.280 lb ae/A (303

- 314 g ae/ha), in a spray volume of 1 gal/A. The application rates used in the study correspond to ~1

- 1.1x the maximum seasonal app lication rate to grasses. An adjuvant (organosilicone, nonionic surfactant, or methylated seed oil) was added to the spray mixture for all of the applications.

Single control and duplicate treated samples of grass forage and hay were harvested from each plot at a PHI of 0 days (approximately 4 hours after application). At two of the trials, four additional sampling intervals were scheduled at PHIs of 3, 7, 14, and 21 days after application to assess residue decline. Samples of hay were allowed to dry in the field for 0

- 28 days after harvest.

The results of the grass field trials for residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl are summarized in Table 8. Following a single foliar broadcast application of the 80% WG formulation of ami nocyclopyrachlor

- methyl WG (at normal or low spray volume) or the 2 lb/gal SL formulation of aminocyclopyrachlor at target rates of ~0.281 ae ai/A and a PHI of 0 days, the major residues found in grass forage and hay were aminocyclopyrachlor

- methyl and ami nocyclopyrachlor . Quantifiable residues of metabolite IN

LXT69 were observed in/on grass forage and hay at up to 0.035 ppm in/on forage and 0.11 ppm in/on hay; residues of IN

- QFH57 or IN

- QGC48 were below the LOQ in/on all samples. Comparison of the resul ts for the side

- by

- side trials reflecting normal and low spray volumes for the 80% WG formulation of aminocyclopyrachlor

- methyl indicated that combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl following application in normal sprayAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 30 of 43 vol umes were higher in/on grass forage in two of three trials and higher in/on grass hay in all three trials. Comparison of the results for the side

- by

- side trials reflecting the 80% WG formulation of aminocyclopyrachlor

- methyl and the 2 lb/gal SL formulatio n of aminocyclopyrachlor at a target rate of 0.281 lb ae/A indicated that combined residues of aminocyclopyrachlor and aminocyclopyrachlor

- methyl were generally slightly higher following application of the aminocyclopyrachlor formulation.

In the residue d ecline trials combined residues of aminocyclopyrachlor

- methyl and aminocyclopyrachlor declined with increasing PHI in grass forage and hay. Residues of IN

LXT69 were near or below the LOQ in most trials; where quantifiable residues were observed, residues declined with increasing harvest interval.

Conclusions : The grass field trial data for aminocyclopyrachlor are adequate to fulfill data requirements. The number and locations of field trials are in accordance with the requirements of OCSPP Guideline 8 60.1500 for grasses , and the use pattern of the field trials adequately reflects the proposed use pattern.

Grass forage and hay samples were analyzed for residues of aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and metabolites IN

- LXT69, IN

- QFH57, and IN

- QGC48 by LC/MS/MS using an adequate method, and the study is supported by adequate s torage stability data . The method LOQ is 0.01 ppm for all analytes in grass forage and hay

. The available field trial data will support tolerance s of 80 ppm for grass forage and 200 ppm for grass hay. The tolerance calculations are presented in Appendix I.

The analytical methods submitted under the subject action do not provide for conversion of residues of aminocyclopyrachlor

- methyl to stoichiometric equiva lents of aminocyclopyrachlor but the residue data presented herein does reflect correction to stoichiometric equivalents. The conversion factor, based on molecular weights (MWs) of 213.6 for aminocyclopyrachlor and 227.6 for aminocyclopyrachlor

- methyl is 0.93849.

As noted above, comparison of the results for the side

- by

- side trials reflecting application of the 80% WG formulation of aminocyclopyrachlor

- methyl and the 2 lb/gal SL formulation of aminocyclopyrachlor i ndicated that combined residues of aminocyclopyr achlor and aminocyclopyrachlor

- methyl were generally slightly higher following application of the aminocyclopyrachlor formulation. When the trial results for each set of trials are compared in terms of ppm
, the results are: For forage: 5 trials with highe r residues following app of the SL ( residues 1.2x higher ) and 1 trial with higher residues following app of the W G ( 1.4 x): For hay: 3 trials with higher residues following app of the SL (1.1

- 1.3x) and 3 trials with higher residues following app of the W G (1.1

- 1.4x). HED does not believe these differences a re significant enough to warrant additional trials for the SL formulation.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 31 of 43 860.1520 Processed Food and Feed

HED does not require residue data for any processed commodities associated with grass. Th erefore, data requirements for processed food and feed are not relevant to this tolerance petition.

860.1650 Submittal of Analytical Reference Standards

An analytical standard for aminocyclopyrachlor acid ( expiration 2013) is curren tly available in the EPA National Pesticide Standards Repository (personal communication between T. Cole, ACB, and Versar , 5/4/11 ) ; however, a standard for aminocyclopyrachlor

- methyl is not currently available . An an alytical reference standard for aminocy clopyrachlor

- methyl must be supplied and supplies replenished as requested by the Repository. The reference standard should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy Nguyen at the following address:

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

- 5350

(Note that the mail will be returned if the extended zip code is not used.)

860.1850 Confined Ac cumulation in Rotational Crops

DER Reference: 48333619.DER
E. I. du Pont de Nemours and Company has submitted a confined rotational crop study with [2

- pyrimidinyl

14 C]aminocyclopyrachlor

- methyl (specific activity 1.64 MBq/mg). The radiolabeled test sub stance was formulated as a 25% WP and applied to sandy loam soil as a single application at 0.067 lb ai/A (75 g ai/ha), equivalent to 0.06 3 lb ae/A (70 g ae/ha) aminocyclopyrachlor , or 0.329 lb ai/A (369 g ai/ha), equivalent to 0.3 09 lb ae/A (3 46 g ae/ha) aminocyclopyrachlor

. The application rates correspond to ~0.2x and ~1.2x the maximum seasonal application rate for grasses. Rotational crops of cabbage, turnip, and field corn were planted at PBIs of 30, 60, 120, and 300 days after soil treatment (DAT) f or cabbage and turnips, and 15, 120, and 300 DAT for corn following soil treatment at 0.067 lb ai/A, and at a PBI of 300 DAT for all crops following application at 0.329 lb ai/A. Samples of immature and mature cabbage and turnips (roots and tops), and cor n (forage, stover, cobs, and grain) were collected at appropriate harvest intervals. The in

- life and analytical phases of the study were conducted by Charles River Laboratories (Tranent, Edinburgh, Scotland).

Following application a t 0.067 lb ai/A, TRR accumulated at >0.01 ppm in: 30

- and 60

- DAT immature and mature cabbage (0.013

- 0.027 ppm); 30

- , 60

- , 120

- , and 300

- DAT immature turnip tops (0.012

- 0.029 ppm); 60

- and 120

- DAT mature turnip tops (0.010

- 0.011 ppm), 30

- day immature turni p roots (0.010 ppm); and 15

- , 120

- and 300

- DAT corn forage (0.011

- 0.091 ppm), stover (0.023

- 0.149 ppm), and grain (0.012

- 0.067 ppm); and 15

- DAT corn cobs (0.024 ppm). Following application at 0.329 lb ai/A, TRR accumulated at >0.01 ppm in immature and mat ureAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 32 of 43 cabbage (0.011

- 0.012 ppm), immature turnip tops (0.085 ppm), and corn forage, stover, cobs, and grain (0.246, 0.262, 0.012, and 0.085 ppm, respectively), planted 300 DAT. These matrices were subjected to further extraction and characterization proced ures.
Approximately 57.3

- 100% TRR was extracted from rotational crop matrices using ACN :water. Nonextractable residues from the 15

- DAT corn forage, stover, and grain and 300

- DAT turnip tops and corn stover following application at 0.067 lb ai/A, and from 300

- DAT turnip tops, and corn forage, stover, and grain following application at 0.329 lb ai/A were subjected to enzyme hydrolysis with α

- amylase ( 50 o C for 72 hours ) followed by a combination of amyloglucosidase and cellulase ( 50 o C for 48 hours ) which released an additional 6.9

- 16.3 % TRR and 3.4

- 13.9% TRR, respectively. Subsequent hydrolysis with 0.01 N NaOH (6 0 o C for 6 hours ) and 1 N HCl (6 0 o C for 6 hours ) released an additional 1.1

- 3.4% TRR and 0.8

- 2.4% TRR, respectively. Remaining nonextractable residues following extraction and hydrolysis procedures were ≤0.009 ppm in all matrices. These procedures adequately extracted the major ity of the residues from rotational crop matrices. Extraction results were normalized; therefore, accountabilities were 100%.

Because samples were stored f rocen f or ≤ 6 months prior to analysis, supporting storage stability data are not required. Extract s were stored for 7

- 163 days prior to analysis. Extracts of 30

- DAT immature cabbage, 60

- DAT immature turnip tops, and 15

- DAT corn stover were reanalyzed following frozen storage for ~14 months to confirm the stability of the metabolite profile.

Residue s were identified and quantitated in the ACN/water extracts and hydrolysates by HPLC. Only three residue components were identified in rotational crops: aminocyclopyrachlor
, aminocyclopyrachlor

- methyl , and IN

- LXT69. aminocyclopyrachlor was the major ide ntified residue and was detected in all crops (40.5

- 96.0% TRR). A minocyclopyrachlor

- methyl was a major metabolite in 30

- and 60

- DAT turnip tops (16

- 18% TRR) and 15

- DAT corn forage and stover (9

- 10% TRR), but was a minor residue component in remaining matr ices ( ≤ 5.6% TRR). IN

- LXT69 was identified at low levels in 15

- DAT corn stover and 300

- DAT corn forage ( ≤ 1.9% TRR).

A minocyclopyrachlor accounted for accounted for 83.1% and 80.1% TRR (0.014 and 0.021 ppm) in 30

- and 60

- DAT immature cabbage and for 60.0% and 60 .6% TRR (0.014 and 0.008 ppm) in 30

- and 60

- DAT mature cabbage following application at 0.067 lb ai/A, and for 54.3% TRR (0.006 ppm ) and 83.0% TRR (0.010 ppm) in 300

- DAT immature and mature cabbage following application at 0.329 lb ai/A. In turnips, amin ocyclopyrachlor accounted for 96.0% TRR (0.010 ppm) in 30

- DAT immature roots, for 57.3

- 83.1% TRR (0.010

- 0.017 ppm) in 30

- , 60

- , 120

- , and 300

- DAT immature tops following application at 0.067 lb ai/A, and for 40.5

- 59.3% TRR (0.004

- 0.007 ppm) in 60

- and 120

- DAT mature turnip tops; residues of aminocyclopyrachlor were 85.6% TRR (0.072 ppm) in 300

- DAT immature turnip tops following application at 0.329 lb ai/A.

In corn, aminocyclopyrachlor accounted for 62.7

- 71.4% TRR (0.007

- 0.176 ppm) in 15

- , 120

- , and 300

- DA T forage following application at 0.067 and/or 0.329 lb ai/A. In stover, aminocyclopyrachlor accounted for 71.9% TRR (0.106 ppm) declining to 45.9% TRR (0.026 ppm) in 15

- , 120

- , and 300

- DAT samples following application at 0.067 lb ai/A, and for 58.0%Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 33 of 43 TRR (0.151 ppm) in 300

- DAT samples following application at 0.329 lb ai/A. Residues of DPX

- MAT 28 in cobs accounted for 58.9% and 43.8% TRR (0.014 and 0.005 ppm) in 15

- DAT and 300

- DAT samples harvested following application at 0.067 and 0.329 lb ai/A, respec tively. Residues in grain were 70.9

- 76.0% TRR (0.009

- 0.064 ppm) in 15

- , 120

- , and 300

- DAT samples following application at 0.067 and/or 0.329 lb ai/A.

A minocyclopyrachlor

- methyl was identified in immature and mature 30

- DAT cabbage, mature 60

- DAT cabbag e, and immature 300

- DAT cabbage following application at 0.329 lb ai/A, and immature turnip roots at 3.3

- 4.6% TRR. In turnip tops, residues accounted for 15.9

- 17.8% TRR (0.002

- 0.003 ppm) in 30

- and 60

- DAT immature and mature tops, and for 5.6% TRR (0.001 ppm) in 120

- DAT immature tops. In 15

- DAT corn forage and stover, aminocyclopyrachlor

methyl accounted for 9.1

- 10.0% TRR (0.009

- 0.013 ppm); residues were identified at ≤ 5.4% TRR in 15

- DAT grain and cobs, and 300

- DAT forage and/or stover and grain following application at 0.067 and/or 0.329 lb ai/A. Remaining residues were characterized as minor unknowns, including an apolar unknown and multicomponent minor unknowns, wh ich accounted for 5.0

- 6.9% TRR (0.012

- 0.018 ppm) and 16.3

- 25.3% TRR (0.038

- 0.064 ppm), respectively, in 300

- DAT corn forage and stover following application at 0.329 ppm, and together accounted for ≤ 0.014 ppm in all remaining matrices.

Based on the resu lts of the study, the petitioner proposed that metabolism of aminocyclopyrachlor

- methyl in rotational crops involves the de

- esterification of aminocyclopyrachlor

- methyl to form the carboxylic acid, aminocyclopyrachlor

. A minocyclopyrachlor undergoes decarb oxylation (to a much lesser extent) to form IN

- LXT69. Succeeding crops grown in soils treated with aminocyclopyrachlor

- methyl would be exposed primarily to aminocyclopyrachlor , the principal soil degradation product.

Conclusions. The confined rotational crop study is acceptable . HED concludes that the nature of the residue in rotational crops is adequately understood and that metabolism in rotational crops is similar to that in primary crops. The study results indicate that residues of aminocyclopyrach lor may exceed the 0.01

- ppm trigger value in turnip tops and corn forage, stover, and grain at a 300

- day P B I following application of aminocyclopyrachlor

- methyl at ~1x the maximum proposed seasonal application rate to grass. Based on the study results lim ited rotational crop field trials are required for aminocyclopyrachlor to establish PBIs and/or tolerances for rotational crops

. Pending submission of the required limited field rotational crop trials, the labels must be revised to prohibit rotation to an y crop other than grasses following application of aminocyclopyrachlor or aminocyclopyrachlor

- methyl.

860.1900 Field Accumulation in Rotational Crops

Based on the results of the confined rotational crop study, limited rotational crop field trials are req uired for aminocyclopyrachlor to establish PBIs and/or tolerances for rotational crops.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 34 of 43 Pending submission of the required limited field rotational crop trials, the labels must be revised to prohibit rotation to any crop other than grasses following appli cation of aminocyclopyrachlor or aminocyclopyrachlor

- methyl.

860.1550 Proposed Tolerances

DuPont has proposed that tolerances for aminocyclopyrachlor residues of concern in crop and livestock commodities be expressed in terms of combined residues of amin ocyclopyrachlor and aminocyclopyrachlor

- methyl

. HED has determined that the proposed tolerance expression as stated in Section F of the petition is appropriate:

Tolerances are established for residues of the herbicide aminocyclopyrachlor, including its m etabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of aminocyclopyrachlor, 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylic acid, and aminocyclopyrachlor methyl ester, methyl 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate, calculated as the stoichiometric equivalent of aminocyclopyrachlor.

The analytical methods submitted under the subject action do not provide for conversio n of residues of amin o cyclopyrachlor

- methyl to stoichiometric equivalents of aminocyclopyrachlor but the residue data presented herein does reflect correction to stoichiometric equivalents . The conversion factor, based on molecular weight s (MW s ) of 213.6 for aminocyclopyrachlor and 227.6 for aminocyclopyrachlor

- methyl is 0.93849.

Adequate crop field trial data reflecting the proposed use patterns were submitted for purposes of establishing tol erances on grass forage and hay. The OECD MRL Calculator ( March 2011 version) was utilized in determining the appropriate tolerance level s. The propose d tolerance s of 65 and 125 ppm for grass forage and hay are too low. T he tolerances should be established at 80 and 200 ppm, respectively.

An acceptable feedi ng study has been submitted in support of the proposed use on grasses. The data indicate that tolerances are needed for milk, and the tissues of cattle, goat, horse, and sheep. The proposed tolerance in milk is too high , and the proposed tolerances for l iver and meat byproducts, except liver are not consistent with Agency policy. L ivestock commodities, i ndividual tolerances in cow, goat, horse, and sheep should be established for meat byproducts at 0. 3 0 ppm , fat at 0.05 ppm, and meat at 0.02 ppm. T he to lerance for milk should be established at 0.0 2 ppm. The tolerances for liver and meat byproducts, except liver should be removed.

There are currently no established Codex, Canadian, or Mexican maximum residue limits (MRLs) for aminocyclopyrachlor ; ther efore, there are no issues of harmonization. An International Residue Limit Status Sheet (IRLS) follows the references in this document.

The proposed and recommended tolerances for aminocyclopyrachlor as a result of the subject action are presented in Ta ble 9 . The proposed tolerances should be revised to reflect the recommended commodities and tolerance levels specified in Table 9

.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 35 of 43 Table 9. Tolerance Summary for Aminocyclopyrachlor. Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comme nts

Cattle, fat 0.07 0.0 5 Cattle, liver 0.06 Not required Based on current Agency policy a separate lower tolerance for liver is not appropriate Cattle, meat 0.02 0.02 Cattle, meat byproducts, except liver 0.4 Not required

Cattle, meat byproduct s

-- 0. 3 0 Based on current Agency policy, the meat byproducts tolerance should be based on the highest residue between liver, kidney, and fat

. Goat, fat 0.07 0.0 5 Goat, liver 0.06 Not required See comment for cattle, liver Goat, meat 0.02 0.02 Goa t, meat byproducts, except liver 0.4 Not required

Goat, meat byproducts

-- 0. 3 0 See comment for cattle, meat byproducts Grass, forage 65 80 * Grass, hay 125 200 * Horse, fat 0.07 0.0 5 Horse, liver 0.06 Not required See comment for cattle, liver Horse, meat 0.02 0.02 Horse, meat byproducts, except liver 0.4 Not required

Horse, meat byproducts

-- 0. 3 0 See comment for cattle, meat byproducts
Milk 0.035 0.0 2 Sheep, fat 0.07 0.0 5 Sheep, liver 0.06 Not required See comment for cattle, l iver Sheep, meat 0.02 0.02 Sheep, meat byproducts, except liver 0.4 Not required

Sheep, meat byproducts

-- 0. 3 0 See comment for cattle, meat byproducts *Based on OECD MRL Calculator References

DP Number: 369057 Subject: Aminocyclopyrachlor: Human Health Risk Assessment for Proposed Uses as an

Herbicide. From: J. Ryman, J. Miller, and T. Morton To: J. Tompkins and M. Ondish Dated: 3/17/10 MRID(s): NoneAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 36 of 43 DP Number: 3 93619 Subject: Aminocyclopyrachlor. Report of the Residues of Concern Knowledgebas e

Subc ommittee (ROCKS)

. From: Ideliz Negrón

- Encarnación To: Aminocyclopyrachlor Risk Assessment Team Dated: 9 / 22 /1 1 MRID(s): NoneAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 37 of 43 

### International Residue Limits

Aminocyclopyrachlor (PC Code 288008; 5/05/11) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3 40 CFR 180. ### : Plant and livestock : Aminocyclopyrachlor, 6

- amino

5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylic acid, and aminocyclopyrachlor methyl ester, methyl 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate, calculated as the stoichiometric equivalent of aminocyclopyrachlor None None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex 3 Cattle, fat 0.0 5 Cattle, meat byproducts 0. 3 0 Cattle, meat 0.02 Goat, fat 0.0 5 Goat, meat byproducts 0. 3 0 Goat, meat 0.02 Grass, forage 80 Grass, hay 200 Horse, fat 0.0 5 Horse, meat byproducts 0. 3 0 Horse, meat 0.02 Milk 0.0 2 Sheep, fat 0.0 5 Shee p, meat byproducts 0. 3 0 Sheep, meat 0.02 Completed: M. Negussie; 05/05/2011

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

2 Mexico adopts US to lerances 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.Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 38 of 43 Attachments:
Appendix I

- Chemical Names and Structures of Aminocyclopyrachlor Residues of Concern Appendix I I

- T olerance Assessment CalculationsAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 39 of 43 Appendix I. Chemical Names and Structures of Aminocyclopyrachlor Residues of Concern.

Common name ; Company code(s) Chemical name Chemical structure

Aminocyclopyrachlor ; DPX

- MAT28 6

- amino

- 5

- chloro

- 2

- cyclo propyl

- 4

- pyrimidinecarboxylic acid

Aminocyclopyrachlor

methyl ; DPX

- KJM44

(methyl ester) methyl 6

- amino

- 5

- chloro

- 2

- cyclopropyl

- 4

- pyrimidinecarboxylate

IN

- LXT69 5

- chloro

- 2

- cyclopropylpyrimidin

4

- ylamine

IN

- Q3007 cyclopropanecarboxamide

IN

- V0977 c yclopropanecarboxylic acid

IN

- QFH57 4

- c yano

- 2

- cyclopropyl

- 1H

imidazole

- 5

- carboxylic acidAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 40 of 43 Common name ; Company code(s) Chemical name Chemical structure

IN

- QGC48 m ethyl

- 4

- cyano

- 2

- cyclopropyl

- 1H

imidazole

- 5

- carboxylateAminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 41 of 43 Appendix II. Tolerance Assessment Calculations.

For each of the grass commodities listed below, the OECD MRL calculator (March 2011 version), was used for calculating recommended tolerances. The statistical goal of the OECD MRL calculator is to prod uce an MRL proposal in the region of the 95 th percentile of the underlying residues distribution. The average residue values used to calculate the tolerances are provided in Table I

- 1. Residue values represent total residues of aminocyclopyrachlor (DPX

M AT28) and aminocyclopyrachlor

- methyl (DPX

- KJM44) converted to parent acid equivalents.

Table I

- 1. Residue data used to calculate tolerance for aminocyclopyrachlor in/on grass commodities. Regulator: EPA Chemical: Aminocyclopyrachlor Crop: Grass forag e Grass hay
PHI: 0 Days 0 Days App. Rate: 0.281 lb ai/A 0.281 lb ai/A Submitter: E.I. du Pont de Nemours and Company E.I. du Pont de Nemours and Company MRID Citation: MRID 48333630 MRID 48333630
Total Aminocyclopyrachlor Residues [Aminocyclopyrachlor + Aminocyclopyrachlor

- m ethyl; ppm] 9.25 26.6 10 28.5 14.3 32.1 14.7 35.2 16.3 35.6 17.5 36.4 18.3 36.7 19.5 41.6 21.1 42.2 25.9 43.8 26.9 47.3 27.1 48.2 28.5 48.5 30.5 49 31.8 54.5 32.9 55.9 33.5 58.7 40.9 72.5 47.3 75 .8 50.3 90.2 14.3 112 18.3 122Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 42 of 43 Grass forage

The dataset used to establish a tolerance for aminocyclopyrachlor on grass forage consisted of field trial data representing application rates of 0.274

- 0.299 lb ai/A aminocyclopyrachlor with a 0

- day PH I. The field trial application rates and PHIs are within 25% of the maximum label application rate and minimum label PHI, respectively. The average residues values used to calculate the tolerance are provided in Table I

- 1. Residue values represent total residues of aminocyclopyrachlor and aminocyclopyrachlor

- m ethyl converted to parent acid equivalents

. Residues of both aminocyclopyrachlor and aminocyclopyrach l or

- m ethyl were quantifiable (LOQ = 0.01 ppm) in/ on all samples of grass forage.

The aminocyc lopyrachlor grass forage dataset was entered into the OECD MRL calculator; the recommended tolerance is 80 ppm for grass forage.

Aminocyclopyrachlor Grass Forage
US and Canada 1 appl @0.281 lb ai/A 0

- day PHI

Total number of data (n) 22
Percenta ge of censored data 0%
Number of non

- censored data 22
Lowest residue 9.250 Highest residue 50.300
Median residue 23.500
Mean 24.961 Standard deviation (SD) 11.334 Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highe st residue 50.300

- Mean + 4 SD 70.298

- CF x 3 Mean 74.884
Unrounded MRL 74.884

Rounded MRL 80Aminocyclopyrachlor Summary of Analytical Chemistry and Residue Data DP#: D38 7442

Page 43 of 43 Grass hay

The dataset used to establish a tolerance for aminocyclopyrachlor on grass hay consisted of field trial data representing applicat ion rates of 0.274

- 0.299 lb ai/A aminocyclopyrachlor with a 0

- day PHI. The field trial application rates and PHIs are within 25% of the maximum label application rate and minimum label PHI, respectively. The average residues values used to calculate the tolerance are provided in Table I

- 1. Residue values represent total residues of aminocyclopyrachlor and aminocyclopyrachlor

- m ethyl. Residues of both aminocyclopyrachlor and aminocyclopyrach l or

- m ethyl were quantifiable (LOQ = 0.01 ppm) in/ on all samples o f grass forage.

The aminocyclopyrachlor grass hay dataset was entered into the OECD MRL calculator; the recommended tolerance is 200 ppm for grass hay.

Aminocyclopyrachlor Grass Hay
US and Canada 1 appl @0.281 lb ai/A 0

- day PHI

Total number o f data (n) 22 Percentage of censored data 0%
Number of non

- censored data 22
Lowest residue 26.600 Highest residue 122.000
Median residue 47.750
Mean 54.241 Standard deviation (SD) 25.684 Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 122.000

- Mean + 4 SD 156.977

- CF x 3 Mean 162.723
Unrounded MRL 162.723

Rounded MRL 200