Page 1 of 28 UNITED STA

TES ENVIRONMENTA L PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDE AND TOXIC SUBSTANCES MEMORANDUM Date: 10 /22 /2009 SUBJECT: Aminopy

ralid and Aminopy

ralid Triisopropanolammonium (TIPA) Salt . Request to Add Uses on Field Corn to Milestone® (EPA Reg. No. 62719 - 519) . Summary of Analy tical Chemistry

and Residue Data . PC Code s : 005100 ( Aminopy ralid) and 005209 ( Aminopy

ralid TIPA S alt) DP Barcode: D 360100 Decision No.: 401475 Registration N o. : 62719 - 519 Petition No.: PP#8F7455 Regulatory Action: Section 3 Registration Risk Assessment Type: NA Case No.: NA T XR No.: NA CAS No.: 150114 - 71 - 9 ( Aminopy ralid) and 566191 - 89 - 7 ( Aminopy

ralid TIPA S alt) MRID No.: 46661301, 46729001, 4672960 1 - 03, 47572601, 47572603 - 04 40 CFR: 180. 610 FROM: Douglas Dotson, Ph.D., Chemist

Risk Assessment Branch I I Health Effects Division , 750 9 P THROUGH: Michael Doherty , Ph.D., Chemist

Richard L oranger, Ph.D., Senior Scientist Risk Assessment Branch I I Health Effects Division , 7509 P TO: Kathry

n Montague/Joanne Miller, RM 23 Herbicide Branch Registration Division, 7 5 0 5 P This document was originally prepared under contract by Dy namac Corporation ( 1901 Research Boulevard, Suite 220 ; Rockville, MD 20850). The document has been reviewed by the Health Effects Division (HED) and revised to reflect current Office of Pesticide Programs (OPP) policies.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 2 of 28 Exe cutive Summary Aminopy ralid is a sy stemic postemergence herbicide which belongs to the py ridine carboxylic acid class of herbicides. It is currently registered for use on rangeland, permanent grass pastures, and wheat . In addition , it is registered for use on wildlife habitat and industrial vegetation management areas, including right - of - way for roads, railroads, and utility lines. Under PP#8F7455 , Dow AgroSciences is proposing the establishment of permanent tolerances for aminopy

ralid ( 2 - py

ridine car boxylic acid, 4 - amino - 3,6 - dichloro - ), expressed as total parent, free and conjugated, in or on the following raw agricultural commodities: Corn, forage ................................ ................................ ....... 0.30 ppm Corn, grain ................................ ................................ ......... 0.20 ppm Corn, stover ................................ ................................ ........ 0.20 ppm Inconjunction with the submitted petition, Dow AgroSciences is requesting an amended Section 3 registration to add uses on field corn to Milestone ® (EPA Reg. No. 62719 - 519), a liquid soluble concentrate (SL) formulation in which aminopy ralid is formulated as the triisopropanolammonium (TIPA) salt. The p roduct contains 40.6% aminopy ralid TIPA salt at an acid equivalent (ae) of 21.1% or 2 lb ae/gal. The product is proposed for postemergence foliar broadcast or spot applications to field corn up to the V6 growth stage at a maximum seasonal rate of 0.027 lb ae/A. P reharvest intervals (PHI s) of 0 day s for grain and 8 day s for forage or silage are proposed. Tolerances for aminopy

ralid are currently

established under 40 CFR §180. 610. Tolerances for residues in/on crop commodities are established under 180.6 10(a)(1) and are expressed in terms of free and conjugated residues of aminopy ralid , calculated as aminopy ralid . T olerances have been established for aspirated grain fractions, grass forage and hay , and wheat bran, forage, grain, hay , and straw. Toleranc es for residues in livestock commodities are established under 180.610(a)(2) and are expressed in terms of aminopy ralid . T olerances have been established for milk and the fat, kidney , meat, and meat by products of cattle, goat, horse, and sheep. The qua litative nature of aminopy ralid residues in field corn is adequately understood for the purposes of this petition based on previously submitted metabolism studies with grass and wheat . Inmetabolism studies reflecting foliar applications to grass and wheat, aminopy ralid was found to be metabolized to a multi - component mixture of water - soluble complexes that consist mostly of isomeric mixtures of acid - and base - labile N - glucosides and glucose ester conjugates of aminopy ralid. HED concluded that the residue s of concern in grass and cereal grain commodities are free and conjugated aminopy ralid. Previously

submitted metabolism studies with lactating goats and laying hens show that most of the administered dose is rapidly excreted (~80% for hens and ~95% for goat). Residues in all poultry commodities, including eggs, were too low to allow identification of residues (residues were less than 0.004 ppm aminopy ralid - equivalents across all commodities). In the goat, residues were less than 0.008 ppm aminopy ralid - equivalents in all commodities except kidney .Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 3 of 28 Inkidney , 80% of the residues (0.07 ppm) were identified as parent aminopy ralid. Although residues in other tissues were too low to permit identification, the weight of the evidence is that the limited amount of aminopy ralid that is not excreted remains as the parent compound. Therefore, the residue of concern in livestock is aminopy ralid. A dequate high performance liquid chromatography (LC) method s with tandem mass spectroscopy

detection (MS/MS) have be en submitted for tolerance enforcement for crop and livestock commodities . T he validated limit of quantitation (L OQ) is 0.0 1 ppm in each matrix. Samples from the submitted field corn crop field trial and processing studies were analy zed using the crop co mmodity

tolerance enforcement method. Samples of grass and wheat commodities from the submitted storage stability study were analy

zed using a previous version of the crop commodity

enforcement method. The submitted storage stability data are adequate t o support the crop field trial study and the field corn process ing study . Acceptable field corn crop field trial studies have been submi tted . T he proposed use on field corn must be amended to remove the proposed PHI s of 0 and 8 day s for grain and forag e , as the submitted data do not support these low PHI s. The data support application to field corn up to the V6 growth stage, with harvest of forage occurring at the dent growth stage or later. The data support the proposed tolerances of 0.30 ppm for fie ld corn forage and 0.20 ppm for field corn grain and stover. T he submitted field corn processing study is adequate and indicates that tolerances are not needed for field corn processed commodities , and that no change in the existing tolerance for aspirated grain fractions is needed as a result of the proposed uses on field corn . The nature of the residue in rotational crops is adequately understood based on a previously submitted study

with lettuce, turnip, and sorghum. No field rotational crop data have been submitted for aminopy

ralid. Although the proposed uses reflect an increased maximum seasonal rate, a limited field rotational crop study with aminopy

ralid does not need to be submitted. The only crops which are likely

to have quantifiable resid ues at the requested plantback intervals (PB I s) are wheat, grasses, and corn, all of which will be treated as primary crops and have tolerances to cover the resulting residues. HED considers the rotation intervals listed on the supplemental label for fiel d corn to be adequate. No changes to the existing tolerances for livestock commodities are needed as a result of the propose d uses on field corn. Codex and Canadian MRL s have been established for residues of aminopy ralid; however, no MRL s have been estab lished for the requested crop commodities. No Mexican MRL s have been established for aminopy

ralid.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 4 of 28 Regulatory Recommendations and Residue Chemistry Deficiencies HED has examined the residue chemistry database for aminopy

ralid. Pen ding submission of a revised Section B (see requirements under Directions for Use) and a revised Section F (see requirements under Proposed Tolerances), there are no residue chemistry issues that would preclude granting Section 3 registration for the reque sted uses of amin o py ralid, or establishment of tolerances for residues of aminopy ralid, as follows: Corn, field, forage ................................ .............................. 0.30 ppm Corn, field, grain ................................ ................................ 0.20 ppm Corn, field, stover ................................ .............................. 0.20 ppm HED recommends that 40CFR §180.610(a)(1) be amended by replacing th e tolerance expression with the following: “Tolerances are established for residues of aminopyalid (4 - amino - 3,6 - dichloro - 2 - py

ridinecarboxylic acid), including its metabolites and degradates, in or on the commodities in the table below. Compliance with th e tolerance levels specified below is to be determined by

measuring only

free and conjugated aminopy ralid.” HED further recommends that 40CFR §180.610(a)(2) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of aminopy ralid, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only

aminopy ralid.” With the review of the interfer ence study and the final report of the grass and wheat storage stability study in this document, all the data requirements that were identified as conditions of registration in the previous aminopy ralid petition (PP#4F6827; D305665, M. Doherty , 7/12/05) have now been satisfied. 860.1200 Directions for Use

 The proposed label must be modified to specify that spray

or spot applications may not be made after the V6 growth stage (BBCH 16) and that forage may not be harvested prior to the dent stage of growth. If the petitioner wishes to support a shorter PHI for field corn forage (or harvest of forage at an earlier growth stage), then adequate crop field trial data reflecting the shorter PHI and/or earlier forage harvest must be submitted. 860.1550 Proposed Tolerances

 The proposed tolerances should be revised to reflect the correct commodity definitions a s specified above and in Table 8 .Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 5 of 28 Background Aminopy ralid is a sy stemic postemergence herbicide th at belongs to the py ridine carboxylic acid class of herbicides. The chemical structure and nomenclature of aminopy ralid and aminopy

ralid TIPA salt are presented in Table 1. The physiochemical properties of the technical grade of aminopy ralid are presented in Table 2. Table 1. Aminopyralid Nom enclature . Chemical structure

N Cl N H

2 Cl

O O H Common name Aminopyralid Company experimental name XDE - 750 IUPAC name 4 - amino - 3,6 - dichloropyridine - 2 - carboxylic acid CAS name 4 - amino - 3,6 - dichloro - 2 - pyridinecarboxylic acid CAS registry number 150114 - 71 - 9 Chemical structure

N Cl N H 2 Cl

O O H N C H 3 O H C H 3 O H C H 3 O H 

## .

Common name Aminopyralid, triisopropanolammonium (TIPA) salt PC Code 005209 Company experimental name XDE - 750 TIPA salt IUPAC name 4 - amino - 3,6 - dichloropyridine - 2 - carboxylic acid - (2RS, 2 ′RS,2′′RS) - 1,1 ′,1′′ - nitrilotripropan - 2 - ol (1:1) CAS name 4 - amino - 3,6 - dichloropyridine - 2 - carboxylic acid compound with 1,1 ′,1′′ - nitrilotris[2 - propanol] (1:1) CAS registry number 566191 - 89 - 7 End - use product (EP) Milestone ® (2 lb ae/gal SL; EPA Reg. No. 6271 9 - 519)Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 6 of 28 TABLE 2. Physicochemical Pro perties of the Technical Grade of Aminopyralid . Parameter Value Reference Melting point/range 163.5 o C MRID 46235703 pH 2.31 at 23.4 o C (1% solution in water) MRID 46235703 Density 1.72 at 20 o C MRID 46235703 Water solubility 2.48 g/L unbuffered water at 18 o C 212 g/L pH 5 buffer at 20 o C 205 g/L pH 7 buffer at 20 o C 203 g/L pH 9 b uffer at 20 o C MRID 46235703

S olvent solubility at 20°C methanol 52.2 g/L acetone 29.2 g/L n - octanol 3.9 g/L ethyl acetate 3.9 g/L 1,2 - dichloroethane 0.2 g/L xylene 0.04 g/L heptane <10 μ g/mL MRID 46235703

Vapor pressure 2.59 x 10 - 8 Pa at 25 o C; 9.52 x 10 - 9 Pa at 20 o C MRID 46235703 Dissociation constant, pKa 2.56 MRID 46235703 Octanol/water partition coefficient, Log(KOW) 0.201 unbuffered water at 19 o C

- 1.76 at pH 5

- 2.87 at pH 7

- 2.96 at pH 9 MRID 46235703 UV/visible absorption spectrum Solution Wavelength λ max, nm Extinction

coefficient L/(mol* cm) Neutral 217 29100 Basic (pH 12.6) 220 26100 Basic (pH 12.6) 245 10150 Acidic (pH 1.4) 217 22800 Acidic (pH 1.4) 270 9140 MRID 46235703

860.1200 Directions for Use The petitioner submitted a proposed supplemental label (pin punched with date 10/1 5 /08) for the 2 lb ae/gal SL product ( Milestone ®; EPA Reg . No. 62719 - 519) for use on field corn. The proposed use directions are presented in Table 3. The supplemental label states that use is subject to all use precautions and limitations imposed by the label on the parent product.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 7 of 28 Table 3 . Summary of Directions for Use of Aminopyralid . Applic. Timing, Ty pe, and Equip. Formul ation

( EPA Reg. No. ) Applic.

Rate (lb ae/A) Max. No.

Applic. per Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations Fie l d Corn and Field Corn grow n for Ensilage Postemergence, Broadcast, Ground 2 lb ae/gal SL

( 62719 - 51 9 ) 0.0089 -

0.027 Not

specified 0.027 0 (grain); 8 (forage or silage) Application is to be

made to actively growing corn before it reaches 20 inches in height or V6 grow

th stage. Spot treatments are to be made at rates equivalent to broadcast application, i n a minimum spray volume of 0. 5 gal/1,000 ft2

. Postemergence, Spot treatment, Ground 0.0002 1 - 0.0006 3 lb ae/1,000 ft2 The label specifies that aerial applications are not to be made unless permitted by EPA - approved supplemental labeling. Under the mixing instructions, the master label specifies that a non - ionic surfactant at 0.25 - 0.5% v/v (1 - 2 quarts per 100 gallons spray ) is recommended to enhance herbicide activity

under adverse environmental conditions. The following rotational crop restrictions are specified: 0 - month plantback interval for wheat; 4 - month plantback interval for grasses and field corn ; 12 - month plantback interval for barley , canola (rapeseed), flax, grain sorghum, mustard, oats, sweet corn, and popcorn; and a 24 - month plantback i nterval for crops not listed. The label also specifies that a field bioassay should be conducted prior to planting any broadleaf crops not listed within 18 months of application. Conclusions . The submitted label is adequate to allow evaluation of the re sidue data relative to the proposed use . The submitted crop field trial data represent application at the proposed maximum seasonal rate (with a nonionic surfactant) and at the proposed growth stage. The proposed PHI s of 0 day s for grain and 8 day s for f orage or silage are not supported by the submitted data. The proposed label should be modified to specify that spray

or spot applications may not be made after the V6 growth stage (BBCH 16) and that forage may not be harvested prior to the dent stage of growth . If the petitioner wishes to support a shorter PHI for field corn forage (or harvest of forage at an earlier growth stage), then adequate crop field trial data reflecting the shorter PHI and/or earlier forage harvest must be submitted. 860.1300 Na ture of the Residue - Plants Residue Chemistry Memo DP# 305665, 7/12/05, M. Doherty (PP#4F6827) The nature of the residue in field corn is adequately understood for the purposes of this petition based on previously

submitted metabolism studies with grass and wheat. The major residue identified in these studies was the parent aminopy ralid (free and conjugated). In the grassAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 8 of 28 metabolism study , there did not appear to be any significant metabolic alterations to the basic structure of the parent compound, wi th the exception of a minor conjugated metabolite formed by addition of a hydroxyl group to the parent molecule and found to be present at <1% total radioactive residues ( TRR) . Aminopy ralid was rapidly

conjugated to yield a multi - component mixture of wate r - soluble complexes which consisted mostly of isomeric mixtures of acid - and base - labile N - glucosides and glucose ester conjugates of aminopy ralid. In the wheat metabolism study , the petitioner concluded that the major metabolic pathway of aminopy

ralid in wheat proceeded via conjugation of aminopy ralid and hydroxylated aminopy ralid with glucose. The petitioner further conclud ed that any metabolites present in wheat which were not identified wer e believed to be conjugates of glucose or similar endogenous c ompounds, based on the fact that most of the radioactivity

in the wheat samples that was not initially detected as the parent could be hydroly

zed to aminopy

ralid. Based on these studies, HED concluded that the residues of concern in grass and cere al grain commodities are free and conjugated aminopy ralid. Additional metabolism data will be required to support uses on non - grass or non - grain commodities. 860.1300 Nature of the Residue - Livestock Residue Chemistry Memo DP# 305665, 7/12/05, M. Doherty (PP#4 F6827) The nature of the residue in livestock is adequately understood based on previously submitted studies with goat and hen. Although the residues in the goat and hen studies were too low to allow adequate characterization/identification of residues, HED concluded that new studies would not be needed. The available metabolism data from the goat, hen, and rat indicate that the majority of the administered aminopy ralid is excreted as unchanged parent in all three species, and the small amount which is a bsorbed remains unchanged. Therefore, the residue of concern in livestock is aminopy

ralid. This finding is supported by the residues of concern for the related compounds picloram and clopy ralid which, in each case, show parent compound to be the major re sidue. 860.1340 Residue Analytical Methods Crop commodities DER References: 46729001 .der.doc

47572602.de 1 .doc MRID 46729601 (no DER; reviewed herein) MRID 46729603 (no DER; reviewed herein) Residue Chemistry Memo DP# 305665, 7/12/05, M. Doherty (PP#4F 6827) Analytical Chemistry Branch Memo DP# 312724, 11/3/05, D. Wright Enforcement method: Dow AgroSciences had previously proposed an L C/MS/MS method, Method GRM 02.31, for the enforcement of tolerances for aminopy ralid residues in grass and wheat commod ities. The method was adequately validated in barley

grain, forage, and straw; grass forage and hay ; sorghum grain, forage, and stover; and wheat grain, forage, and straw.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 9 of 28 Adequate ILV data were submitted for the method using grass forage and wheat grain , and adequate radiovalidation data were submitted for the extraction procedures using samples of grass and wheat commodities bearing incurred residues from the metabolism studies . Method GRM 02.31 was sent to ACB for review . It was concluded that the method was adequate for enforcement purposes and that no laboratory validation at ACB was needed. ACB concluded that the method needed confirmatory procedures . T he single ion transition monitored in the method is not considered sufficient for positive co nfirmation of analy te information. ACB additionally

noted two errors in the analy te peak response area and quantitation ratio data reported in one of the representative chromatograms in the independent laboratory validation study (MRID 46235712) . Inre view of M ethod GRM 02.31 , HED expressed concern that the proposed enforcement method m ight not be able to differentiate between aminopy ralid, picloram, and clopy ralid, and requested that the petitioner complete an interference study using these three compo unds. Inresponse, the petitioner submitted a revised version of Method GRM 02.31 in MRID 46729601. The revised method includes instructions for monitoring two additional MS/MS transitions for confirmation of residue identity . In addition, the petitio ner submitted MRID 46726903, a revised version of the ILV study , in which the two errors noted by ACB in the representative chromatogram were corrected. Inaddition, Dow AgroSciences submitted the requested interference study for the derivatization and LC /MS/MS analy sis procedures of Method GRM 02.31. To investigate the potential inference of picloram and clopy ralid in the determination of aminopy ralid, the petitioner prepared analy tical standards of picloram and clopy ralid, as well as aminopy

ralid, and derivatized the standards to form the 1 - butyl esters of the compounds using the procedures of Method GRM 02.31. The derivatized compounds were then analy zed by L C/MS/MS. The analy sis of the 1 - butyl esters of aminopy ralid, clopy

ralid, and picloram demo nstrated that the three compounds have different retention times and that there was no interference in the ion transitions. Therefore, clopy ralid and picloram do not interfere in the determination of aminopy ralid residues using Method GRM 02.31 . The pe titioner noted that , since the original aminopy ralid methods were developed, minor changes in the LC conditions and MS/MS parameters have been made to improve the sensitivity and selectivity

of the method, including the addition of two ion transitions to m onitor for the confirmation of aminopy

ralid residues. Representative chromatograms from the analysis of a grass forage sample were provided for the quantitation ion transition and the two confirmation ion transitions. T he changes in the LC and MS/MS cond itions are reflected in the revised methods that were submitted with this tolerance petition : Method GRM 07.07 for crop commodities and Method GRM 07.08 for livestock commodities ( see below ). With PP# 8F7455, Dow AgroSciences has proposed an LC /MS/MS me thod , Method GRM 07.07, for the determination of residues of aminopy ralid in crop commodities (wet, dry , acidic, and oilyAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 10 of 28 crops). The method description indicates that Method GRM 07.07 supersedes Method 02.31. The major differences between the two method s are that Method GRM 02.31 uses a different internal standard ( 13 C 2 15 N - aminopy ralid) and only

includes instructions for the determination of residues in barley , sorghum, wheat, and grass commodities. Briefly , residues are extracted from homogenized agricultural commodities using 0.1 N NaOH, which hydroly

zes bound residues and base - labile conjugates to yield free aminopy ralid . T he hydroly sate is acidified with 2 N HCl. Oil samples are extracted with acetone and the extract is evaporated to dry

ness, red issolved in hexane, and partitioned into water. The aqueous phase is mixed with 0.2 N NaOH to hydroly ze bound residues and base - labile conjugates to yield free aminopy ralid, and then acidified with 3 N HCl. For both crop samples and oil samples, the acid ified extract is heated at 80°C for 90 minutes, which hydroly zes acid - labile conjugates to yi eld free aminopy

ralid and further solubilizes bound residues. The extract is then purified by anion - exchange solid phase extraction (SPE), using ethyl acetate:tri fluoroacetic acid (99:1, v:v) to elute residues. An internal standard ( 13 C 2 2 H 15 N - aminopy ralid) is added to the eluate, which is evaporated to dry

ness, reconstituted in acetonitrile:py ridine:1 - butanol (22:2:1, v:v:v; derivatization coupling reagent) and de rivatized with butyl chloroformate to form the 1 - butyl esters of the analy

te and the internal standard. The mixture is diluted with a solution of methanol:water (40:60, v:v) containing 0.05% formic acid and 5 mM ammonium formate for LC /MS/MS analy sis. Th e LOQ and limit of detection (LOD) are 0.01 and 0.003 ppm, respectively , for aminopy ralid in each tested matrix. Method GRM 07.07 was adequately validated using samples of untreated wet crops (broccoli and tomato), dry

crops (wheat forage, grain, and straw, corn forage and grain, and grass forage and straw), acidic crops (lemon whole fruit and orange peel, pulp, and whole fruit), and oily crops (palm oil and sunflower seed) fortified with aminopy ralid at 0.01 and 2 ppm for all crops other than grass forage and straw, and at 0.01 and 50 ppm for grass forage and straw. The recovery ranges for these matrices were 75 - 102% for wet crops (average ± standard deviation: 86% ± 6.6%), 70 - 102% for dry

crops (86% ± 8.3%), 72 - 105% for acidic crops (88% ± 7.4%), and 82 - 106% for oily

crops (93% ± 6.5%). The fortification levels and samples used in method validation are adequate to bracket expected residue levels. Although field corn stover, aspirated grain fractions, and processed commodities were not included in the validation study , adequate concurrent method recovery data for these commodities were included with the field corn field trial and processing studies submitted with this petition . The method includes instructions for monitoring up to three ion transitio ns for aminopy ralid; therefore, confirmatory

analy sis procedures are not needed. The method is very

similar to the current enforcement method, L C/MS/MS Method GRM 02.31, for which adequate radiovalidation and independent laboratory validation data have be en submitted. Because Method GRM 07.07 is considered to be an improvement to Method GRM 02.31, no independent laboratory validation or validation by ACB is needed.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 11 of 28 Data collection method: Method GRM 07.07 was used for data collection in samples of cor n forage, grain, stover, aspirated grain fractions, and processed commodities from the crop field trial and processing studies submitted with this petition . Overall concurrent method recoveries ranged 69 - 90% from forage, 75 - 97% from grain, 72 - 94% from sto ver , and 75 - 98% from corn processed commodities. Samples of grass and wheat commodities from the storage stability study were analy

zed using Method GRM 02.31 ; overall concurrent method recoveries ranged 71 - 106% . Conclusions . The submitted crop analy tica l method data are adequate to satisfy data requirements. Method GRM 07.07 satisfies all requirements for an enforcement method for crop commodities. The method will be forwarded to the FDA for publication in PAM Vol. II. T he submitted interference stu dy satisfies the data requirements for this study identified in PP#4F6827 ( Memo, D305665, M. Doherty , 7/12/05 ) . Li vestock commodities DER References: 47572602.de 2 .doc MRID 46729602 (no DER; reviewed herein) Residue Chemistry Memo : D305665, M. Doherty , 7/12/05 (PP#4F6827) Analytical Chemistry Branch Memo : D312724, D. Wright, 11/3/05 Enforcement method: Dow AgroSciences had previously proposed an L C/MS/MS method, Method GRM 03.18, for the enforcement of tolerances for aminopy ralid residues in ruminant milk and tissues. The method was adequately validated in bovine whole milk, cream, skimmed milk, fat, kidney , liver, and muscle , and adequate ILV data were submitted for the method using bovine milk and kidney . RAB2 concluded that radiovalidation data were not needed for the method because the extraction procedures are very similar to those used in the goat metabolism study . The method was sent to ACB for review . It was concluded that the method was adequate for enforcement purposes and that no laboratory validation at ACB was needed. ACB concluded that the method needed confirmatory procedures . ACB additionally noted that step 9.3.17 of Method GRM 03.18 referred to Section 7.5.1 of the method, which does not exist. Inresponse, the petitioner sub mitted a revised version of Method GRM 03.18 in MRID 46729602. The revised method includes instructions for monitoring two additional MS/MS transitions for confirmation of residue identity . In addition, the erroneous reference to Section 7.5.1 was remove d. Inreview of Method GRM 03.18, HED expressed concern that the proposed enforcement method m ight not be able to differentiate between aminopy ralid, picloram, and clopy ralid, and requested that the petitioner complete an interference study using these three compounds. The requested inference study for Method GRM 02.31 has been submitted (see above). Because the derivatization and L C/MS/MS analy sis procedures of Method GRM 02.31 are the same as those of Method GRM 03.18, the interference study is suffi cient to demonstrate that clopy ralid and picloram will not interfere in aminopy ralid determination using Method GRM 03.18.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 12 of 28 With PP# 8F7455, Dow AgroSciences has proposed LC /MS/MS Method GRM 07.08 for the determination of residues of aminopy ralid in cattle and poultry tissues, milk, and eggs. The method description indicates that Method GRM 07.08 supersedes Method GRM 03.18. The major differences between the two methods are that Method GRM 03.18 uses a different internal standard ( 13 C 2 15 N - aminopy ralid) and only

includes instructions for the determination of residues in bovine commodities (muscle, fat, liver, kidney , and milk). Briefly , sodium bicarbonate is added to homogenized livestock commodities and the mixture is extracted using methanol. The extra ct is purified by anion - exchange SPE, using ethyl acetate:trifluoroacetic acid (99:1, v:v) to elute residues. An internal standard ( 13 C 2 2 H 15 N aminopy ralid) is added to the eluate, which is evaporated to dry ness, reconstituted in acetonitrile:py

ridine:1 - butanol (22:2:1, v:v:v; derivatization coupling reagent) and derivatized with butyl chloroformate to form the 1 - butyl esters of the analy te and the internal standard. The mixture is diluted with a solution of methanol:water (40:60, v:v) containing 0.05% for mic acid and 5 mM ammonium formate for L C/MS/MS analy sis. The L OQ and LOD are 0.01 and 0.003 ppm, respectively , for aminopy ralid in each tested matrix. The method was adequately validated using samples of untreated cattle milk, kidney, and fat and poultr y egg, liver, and muscle fortified with aminopy ralid at 0.01 and 2 ppm. The recovery ranges for these matrices were 90 - 119% for bovine matrices (average of 98% with a standard deviation of 5.7%) and 82 - 111% for poultry matrices (average of 95% with a stan dard deviation of 5.9%). The fortification levels and samples used in method validation are adequate to bracket expected residue levels. R adiovalidation data are not needed for Method GRM 07.08 as the extraction procedures are very similar to those of Me thod GRM 03.18 . The method includes instructions for monitoring up to three ion transitions for aminopy ralid; therefore, confirmatory

analy sis procedures are not needed. The method is very

similar to the current enforcement method, L C/MS/MS Method GRM 03.18. Because Method GRM 07.08 is considered to be an improvement to Method GRM 03.18, no independent laboratory

validation or validation by ACB is needed. Conclusions . The submitted livestock analy tical method data are adequate to satisfy data requi rements. Method GRM 07.08 satisfies all requirements for an enforcement method for livestock commodities. The m ethod will be forwarded to FDA for publication in PAM Vol. II. 860.1360 Multiresidue Methods Residue Chemistry Memo D305665, M. Doherty , 7 /12/05 Adequate multiresidue method testing data have been submitted previously for aminopy ralid . The results of the study

indicate that the FDA multiresidue methods in PAM Vol. Iare not suitable for the determination of aminopy ralid.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 13 of 28 860.1380 Stor age Stability DER Reference: 46661301.der.doc Residue Chemistry Memo D305665, M. Doherty , 7/12/05 Dow AgroSciences has submitted the final report of a storage stability study with aminopy

ralid on grass forage and hay , and wheat grain and straw. An int erim report for this study , reflecting storage intervals of up to ~6 months, was previously reviewed under PP#4F6827 . Samples of untreated grass forage, grass hay , wheat grain, and wheat straw were fortified with aminopy ralid at 0.1 ppm and stored frozen (~ - 20oC). Storage intervals tested were 0, 28, 130, 187, and 488 day s (grass forage and hay ) or 0, 113, 168/175, 273, and 469 days (wheat grain and straw). Samples of grass hay

and forage , and wheat grain and straw were analy zed for residues of aminopy ra lid using L C/MS/MS Method GRM 02.31. The method was adequate for data collection based on acceptable concurrent method recoveries; the reported LOQ was 0.01 ppm for each commodity . The study results indicate that residues of aminopy ralid are stable durin g frozen storage for up to ~16 months in/on grass forage and hay , and for up to ~15 months in/on wheat grain and straw. The storage duration s and conditions of samples from the crop field trial and processing s tudies submitted to support this petition ar e presented in Table 4 . Table 4 . Summary of Storage Conditions and Duration s of Samples from Field Corn Crop Field

Trial and Processing Studies. Matrix Storage Temperature (°C) Actual Storage Duration 1 Interval of Demonstrated Storage Stability Fi eld corn forage ~ - 20 435 - 518 days (14.3 - 17.0 months) Residues of aminopyralid are stable during frozen storage for up to ~16 mo nths in/on grass forage and hay , and for up to ~15 mo nths in/on wheat grain and straw . Field corn grain 375 - 448 days (12.3 - 14.7 mo nths) Field corn stover 377 - 448 days (12.4 - 14.7 months)

Field corn AGF 350 days (11.5 months) No storage stability data are available for field corn processed commodities. Flour 355 days (11.7 months) Grits 384 days (12.6 months) Meal 355 days (11.7 months) Starch 341 days (11.2 months) Refined oil (wet milled) 387 days (12.7 months) Refined oil (dry milled) 350 days (11.5 months) 1 From harvest/collection to extraction for analysis. Conclusions . The submitted storage stability study is adequate to fulfill data requirements for samples of field corn forage, grain, and stover from the submitted field trial and processing studies. The data indicate that no correction for residue decline during storage will be needed for these co mmodities.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 14 of 28 The data are also adequate to support the storage conditions and durations of field corn processed commodities from the processing study submitted to support this petition. A lthough a storage stability study with aminopy

ralid residues in fiel d corn processed commodities was not submitted , the available storage stability data for the wheat and grass commodities will be considered to be adequate to support the field corn processing study . The OECD guideline “Stability of Pesticide Residues in S tored Commodities” (adopted 10/16/2007) states that storage stability data for processed foods are not needed if residue decline is not observed across the range of five commodity

categories. In this case, HED considers the data for grain and grass commod ities to be adequate in light of the minimal metabolism of aminopy ralid in living plants. Conjugation is the only

significant metabolic pathway , and the resulting conjugates are determined by

the analy tical method. The dates of analy sis were not provide d for the subject field trial and processing studies. For future submissions, the petitioner should note that dates of extraction and analy sis should be provided for all samples. Submission of the final report of the grass and wheat storage stability stu dy satisfies the data requirements for storage stability identified in PP#4F6827 ( Memo, D305665, M. Doherty , 7/12/05 ) . No correction for residue decline is needed for any of the grass or wheat commodity samples submitted under PP#4F6827 . 860.1400 Water, Fish, and Irrigated Crops There are no proposed uses that are relevant to this guideline topic . 860.1460 Food Handling There are no proposed uses that are relevant to this guideline topic. 860.1480 Meat, Milk, Poultry, and Eggs Residue Chemistry Memo : D305665, M. Doherty, 7/12/05 There are several livestock feedstuffs associated with the registered and proposed uses of aminopy ralid, including AGF (and milled by products); grass forage , grass hay , field corn grain, field corn forage, field corn stover , wheat grain, wheat forage, wheat hay , and wheat straw . The dietary burdens of aminopy

ralid to livestock, based on reasonably balanced diets, are presented in Table 5. The estimated dietary burdens are 8.7 ppm for beef cattle, 45 ppm for dairy cattle, 0. 15 ppm for poultry , and 0.17 ppm for swine.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 15 of 28 Table 5 . Calculation of Dietary Burdens of Aminopyralid Residues to Livestock. Feedstuff Ty pe 1 % Dry Matter2 % Diet2 Established/ Recommended Tolerance (ppm) Dietary Contribution (ppm) 3 Beef Cattle Grass hay R 88 15 50 8.5 Corn, field, grain CC 88 80 0.20 0.18 PC without registered uses PC -- 5 -- -- TOTAL BURDEN -- -- 100 -- 8.7 Dairy Cattle Grass, forage R 25 45 25 45 Corn, field, grain CC 88 45 0.20 0.10 PC without registered uses PC -- 10 -- -- T OTAL BURDEN -- -- 100 -- 45 Poultry Corn, field, grain CC 88 75 0.20 0.15 PC without registered uses PC -- 25 -- -- TOTAL BURDEN -- -- 100 -- 0.15 Swine Corn, field, grain CC 88 85 0.20 0.17 PC without registered uses PC -- 15 -- -- TOTAL BURDEN -- -- 100 -- 0.17 1 R: Roughage; CC: Carbohydrate concentrate; 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) fo r poultry and swine. Ruminants : The dietary

burdens of aminopy

ralid to livestock were previously calculated to be 60 ppm for beef and dairy

cattle and 0.075 ppm for swine. Based on an a dequate dairy cattle feeding study , reflecting dosing of dairy cattle with aminopy

ralid at levels of 32.8, 64.5, 181.5, or 644.7 ppm in the diet , RAB2 concluded that tolerances were needed for livestock commodities at 0.03 ppm for milk; 0.02 ppm for the meat and meat by products, excluding kidney , of cattle, goats, horses , and sheep; 0.02 ppm for the fat of cattle, goats, horses, and sheep; and 0.30 ppm for the kidney

of cattle, goats, horses, and sheep. Itwas also concluded that no tolerances were needed for swine commodities. Because the re - calculated dietary burdens for beef and dairy cattle are lower than the previously calculated values, no changes to the existing tolerances for cattle, goat, horse, and sheep commodities are needed to support the proposed uses. The lowest dosing level in the cattle feeding study represents 190x the maximum theoretical dietary burden to swine. Aminopy ralid residues in milk and tissues from the lowest dosing level in the cattle feeding study were ≤0.01 ppm in all commodities except kidney and were 0.10 ppm in kidney . HED concludes that tolerances for hog commodities are not needed to support the proposed and registered uses of aminopy ralid.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 16 of 28 Poultry : No poultry

feeding study

with aminopy

ralid has been submitted. RAB2 previously concluded that tolerances for poultry commodities were not needed based on the results of the poultry metabolism study and the previously calculated dietary

burden of 0.075 ppm . The poultry metabolism study represented a dosing level of 12 ppm and TRR were <0.01 ppm in eggs and all poultry

tissues at this dosing level. The dosing level corresponds to 80x the current dietary burden aminopy

ralid to poultry . Therefore, HED concludes that the proposed and registered uses of aminopy ralid result in a 40 CFR §180.6(a)(3) situation for poultry commodities; i.e., there is no reasonable expectation of finite residues in poultry commodities. No poultry

feeding study is needed to support the subject petition. I f additional uses of aminopy ralid with significant poultry feed items are proposed in the future, then a po ultry feeding study

m ight be required. 860.1500 Crop Field Trials DER Reference: 47572601.de1.doc (includes review of MRID 47572603) Dow AgroSciences submitted field trial data for aminopy ralid on field corn. Twenty field corn trials were conducted in the United States during the 2006 growing season . One trial each was performed in Zones 1 (PA), 2 (GA), and 6 (TX). Seventeen trials were performed in Zone 5 (IA (3), IL (3), I

N (1), MI(1), MN (2), MO (1), ND (2), NE (2), OH (1), and WI(1)). Each treated plot received a single foliar application of an SLformulation containing the TIPA salt of aminopy

ralid at 2 lb ae/gal. Applications were made at the 4 - to 6 - leaf growth stage (BBCH 14 - 16 or V4 - V6). There were two treated plots at each location. One treated plot received an application at ~0.031 lb ae/A (~1x the proposed maximum seasonal rate) and the other plot received an application at ~0.062 lb ae/A ( ~ 2x) . Applications were made in ~15 - 24 gal/A spray

volumes, using ground equipment. A non - ionic surfactant was added to the spray mixture at ~0.25% (v/v). Field corn commodities were harvested at normal harvest times . F orage was harvested at the dent stage, at a 60 - to 87 - day preharvest interval (PHI), and grain and stover were harvested at maturi ty , at a 105 - to 138 - day PHI . In addition, to evaluate residue decline , forage samples were harvested at the W isconsin trial and at one of the I llinois trial s at 0 - , 7 - , 13 - to 14 - , 21 - , and 28 - day PHI s. Samples of field corn forage, grain, and stover we re analy zed for residues of aminopy ralid using LC /MS/MS Method GRM 07.07. The validated L OQ was 0.01 ppm for each matrix. The method was adequate for data collection based on acceptable concurrent method recovery data. Sample storage conditions and durations are reported in Table 4. Adequate storage stability data are available to support the storage conditions and durations of samples from the submitted field corn study . A summary

of the study

results is presented in Table 6. Following foliar appli cation of the 2 lb ae/gal SL formulation at approximately a 1x application rate ( 0.030 - 0.034 lb ae/A ) , maximum residues of aminopy

ralid were 0.262 ppm in/on forage (60 - to 87 - day PHI ), 0.164 ppm in/onAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 17 of 28 grain (105 - to 138 - day

PHI ), and 0.176 ppm in/on stover (105 - to 138 - day PHI ). Following foliar application at approximately a 2x application rate ( 0.060 - 0.069 lb ae/A ) , maximum residues of aminopy ralid were 0.293 ppm in/on forage, 0.212 ppm in/on grain, and 0.387 ppm in/on stover. Inthe four forage resid

ue decline trial s , average residues of aminopy ralid decreased from the 0 - day to either the 14 - day

PHI or 21 - day

PHI and then generally

did not decrease further (from the 14 - or 21 - day

PHIto harvest at 66 or 72 days posttreatment). Table 6 . Summary of Res idue Data fromCrop Field Trials with Aminopyralid . Crop matrix PHI

(days) Total Applic.

Rate (lb ai/A) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. FIELD CORN (proposed use = 0.027 lb ai/A total application rate , 0 - day PHI for grain and 8 - day for forage and silage ) Field corn forage 60 - 87 0.030 - 0.034 40 <0.01 0.262 0.226 0.041 0.059 0.053 0.060 - 0.069 39 0.018 0.293 0.240 0.083 0.105 0.069 Field corn grain 105 - 138 0.030 - 0.034 40 <0.01 0.164 0.155 0.090 0.036 0.032 0.060 - 0.069 40 <0.01 0.212 0.209 0.049 0.060 0.048 Field corn stover 105 - 138 0.030 - 0.034 40 <0.01 0.176 0.153 0.032 0.048 0.041 0.060 - 0.069 40 0.020 0.387 0.360 0.059 0.084 0.077 1 HAFT = Highest average field trial result. Conclusions . The submitted field cor n crop field trial data are adequate to fulfill data requirements provided the proposed use is amended as requested under 860.1200. The number and locations of the corn field trials are in accordance with those specified in OPPTS Guideline 860.1500 for us e on field corn. Field trials were conducted at ~1x the proposed maximum seasonal rate , and application was made at the growth stage specified on the proposed label. However, it should be noted that the proposed PHI s of 0 day s for grain and 8 days for fo rage and silage are not supported. The available data support the proposed tolerances of 0.30 ppm for field corn forage, 0.20 ppm for field corn grain, and 0.20 ppm for field corn stover . R efer to Appendix I for the tolerance calculation. Residue data for field corn aspirated grain fractions were submitted and are discussed below with the field corn processing data. 860.1520 Processed Food and Feed DER Reference: 47572601.de2.doc (includes review of MRID 47572604) Dow AgroSciences submitted a proces sing study for aminopy

ralid on field corn. During the 2006 growing season, a single field corn trial was conducted in the United States in Zone 5 (I llinois ). A single foliar broadcast application of an SL formulation containing the TIPA salt of aminopy ra lid at 2 lb ae/gal was made to field corn at the BBCH 14 - 15 growth stage at 0.060 lbAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 18 of 28 ae/A (~2x the proposed maximum seasonal rate) . The application was made using ground equipment in a 17.4 gal/A spray volume and a non - ionic surfactant was added to the sp ray mixture. A single bulk sample of field corn grain was harvested at a 138 - day PHI , and processed using simulated commercial procedures into aspirated grain fractions (AGF), as well as flour, grits, meal, and refined oil (dry milling), and starch and re fined oil (wet milling). Samples of field corn grain raw agricultural commodity (RAC) and processed fractions were analy zed for residues of aminopy ralid using L C/MS/MS Method GRM 07.07. The validated LOQ was 0.01 ppm for each matrix. The method was adeq uate for data collection based on acceptable concurrent method recovery data. Sample storage conditions and durations are reported in Table 4. Adequate storage stability data are available to support the storage conditions and durations of samples of f ield corn grain and processed commodities from the processing study . Residues of aminopy

ralid were 0.0787 ppm in field corn grain (RAC) harvested 138 days after a single foliar application of aminopy ralid at 0.060 lb ae/A. Residues of aminopy ralid were 0 .0270 ppm in AGF, 0.0747 ppm in flour, 0.0886 ppm in grits, 0.1019 ppm in meal, and <0.01 ppm in starch and wet and dry

milled refined oil. The processing factors for field corn processed commodities are presented in Table 7. R esidues of aminopy ralid d id not concentrate in corn AGF (0.3x), flour (0.9x), starch (<0.1x), or refined oil (<0.04x for both wet and dry milled) , but concentrate d slightly

in corn grits (1.1x) and meal (1.3x). The observed processing factors are below the maximum theoretical concentration factor of 25x for corn (OPPTS 860.1520, Table 1) . Table 7 . Summary of Processing Factors for Aminopyralid .

RAC Processed Commodity Processing Factor Field corn , grain Aspirated grain fractions 0.3x Flour 0.9x Grits 1 .1x Meal 1.3x Refined oil (dry milling) <0.04x Refined oil (wet milling) <0.04x Starch <0.1x Conclusions . The submitted processing data are adequate to satisfy data requirements. The processing data indicate that no tolerances are needed for fi eld corn flour, starch, or refined oil, and that no change in the existing tolerance for aspirated grain fractions, at 0.20 ppm, is needed as a result of the proposed uses on field corn. The processing data indicate that aminopy ralid residues m ight concentrate in field corn grits and meal. Based on the HAFT residues for aminopy ralid in/on field corn grain (0.155 ppm), and the processing factors, expected residues of aminopy ralid in corn grits and meal following treatmentAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 19 of 28 at 1x would be 0.17 and 0.20 ppm, respectively . Because these values are not greater than the proposed tolerance of 0.20 ppm for field corn grain, no tolerances are needed for grits and meal . 860.1650 Submittal of Analytical Reference Standards An analy tical stan dard for aminopy ralid is currently

available in the EPA National Pesticide Standards Repository , with an expiration date of 8/28/2010 ( electronic communication , Dallas Wright ( ACB ) to D. Dotson , 9 /1 5 /20 0 9 ). 860.1850 Confined and Field Accumulation in Ro tational Crops Residue Chemistry Memo : D305665, M. Doherty, 7/12/05 (PP#4F6827) A confined rotational crop study was submitted previously . In that study , [2,6 - 14 C]aminopy ralid was applied directly

to sandy loam soil in lined wooden boxes at 0.009 lb ai /A, which was 1x the proposed maximum seasonal rate for wheat (the only annual crop in PP#4F6827) , and r otational lettuce, sorghum, and turnips were planted at plantback intervals (PBI s) of 90 and 120 day s . TRR acc umulated at ≥0.01 ppm in 90 - and 120 - day PBI early sorghum forage (0.027 ppm and 0.017 ppm, respectively

), 90 - day PBI sorghum stover (0.027 ppm), and 120 - day PBI mature turnip tops (0.010 ppm); residues in all other rotational crop commodities ranged <0.00 1 - 0.007 ppm. TRR were generally found to decrease from the 90 - day PBIto the 120 - day

PBI . Total identified residues ranged from 17 to 44% TRR in sorghum early forage and stover as well as in turnip tops , and consisted entirely of free aminopy

ralid . R esi due profiles were similar between the matrices. Aminopy

ralid was found at 0.012 ppm in 90 - day PBIsorghum early

forage, 0.005 ppm in 120 - day

PBI sorghum early

forage, 0.005 ppm in 90 - day PBI sorghum stover , and 0.002 ppm in 120 - day

PBI turnip tops . In PP #4F6827 , HED concluded that the residues of concern in rotational crop commodities are the same as for primary crop commodities, free and conjugated aminopy ralid . HED further concluded that there is potential for quantifiable residues of aminopy ralid in r otated cereal grain forage at a 3 - month PBI . No field rotational crop study was submitted. Itwas concluded that the available rotational crop data support a 0 - day plantback interval for wheat and a 4 - month plant - back interval for barley , canola, flax, grasses, field corn, grain sorghum, oats, mustard, popcorn, and sweet corn (the requested rotated crops in PP#4F6827) . With the proposed use on field corn, the maximum seasonal rate to annual crops has increased from 0.009 lb ai/A to 0.027 lb ai/A. The av ailable rotational crop data reflect application at a rate of 0.3x the proposed maximum seasonal rate. Because the identified residues in the confined rotational crop study consisted solely of free and conjugated aminopy ralid, a new confined rotational crop study (conducted at 0.027 lb ai/A) will not be required to support the proposed use. Although the available confined data indicate that quantifiable residues of aminopy ralid could occur in grasses and cereal grain foliage with a PBI of 4 months, the on ly crops with requested PBI s of less than one year (i.e., wheat, grasses, and field corn) will be treated as primary

crops and will have tolerances. Therefore, the petitioner does not need to submit a limited field rotational crop study for aminopy

ralid r eflecting a PBI

of 4 months . HED considers the rotation intervals listed on the supplemental label for field corn to be adequate.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 20 of 28 The supplemental label specifies that wheat may be planted at any

time after harvest. Grasses and field corn may

be planted at a 4 - month plantback interval. Barley , canola (rapeseed), flax, grain sorghum, mustard, oats, sweet corn, and popcorn may be planted at a 12 - month plantback interval. The crop rotational interval for all other crops not listed on the label is 24 month s. 860.1550 Proposed Tolerances DowAgroSciences has proposed tolerances for residues of aminopy ralid (2 - py

ridine carboxylic acid, 4 - amino - 3,6 - dichloro - ), expressed as total parent, free and conjugated, in/on field corn commodities . T he proposed toleranc es are listed in Table 8 . HED recommends that 40CFR §180.610(a)(1) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of aminopyalid (4 - amino - 3,6 - dichloro - 2 - py

ridinecarboxylic acid), including it s metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by

measuring only

free and conjugated aminopy ralid.” HED further recommends that 40CFR §180.610(a)(2) be amended by replacing the tolerance expression with the following: “Tolerances are established for residues of aminopy ralid, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specifi ed below is to be determined by measuring only

aminopy ralid.” Codex and Canadian MRL s have been established for residues of aminopy ralid; however, no MRL s have been established for the requested crop commodities. No Mexican MRL s have been established fo r aminopy

ralid. Adequate field trial data have been submitted for field corn . The Agency ’s Guidance for Setting Pesticide Tolerances Based on Field Trial Data was u sed for determining appropriate tolerance levels for field corn raw agricultural crop comm odities . S ee Appendix Ifor tolerance calculations. The available data will support the proposed tolerances of 0.30 ppm for field corn forage, 0.20 ppm for field corn grain, and 0.20 ppm for field corn stover. T he field corn processing study is adequate . It i ndicates that no tolerances are required for field corn flour, grits, meal, refined oil, or starch , and that no change in the existing tolerance for aspirated grain fractions, at 0.20 ppm, is needed as a result of the proposed uses on field corn. No changes to the existing tolerances for livestock commodities are needed as a result of the proposed uses.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 21 of 28 The proposed tolerances should be revised to reflect the correct commodity definitions as specified in Table 8 . Table 8 . Tolerance Sum ma ry fo r Aminopyralid. Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments ; C orrect Commodity D efinition Corn, forage 0.30 0.30 Corn, field, forage Corn, grain 0.20 0.20 Corn, field, grain Corn, stover 0.20 0.20 Corn, field, stover

R eferences D305665 , Aminopy

ralid. Petition for the Establishment of Permanent Tolerances for Use of Aminopy ralid on Grasses and Wheat. Summary of Analy tical Chemistry

and Residue Data. PP#4F6827 , M. Doherty , 7/12/05 , MRIDs: 46235708 - 46235712, 46235714, 46235716 - 46235719, 46235721 - 46235725 D312724 , PP# 4F6827. Review of Method for the Establishment of Permanent Tolerances in Aminopy ralid in/on Plant and L ivestock Commodities. ACLProject #:B05 - 12 , D. Wright , 11/3/05 , M RIDs: 46235712, 46235714, 462357 16, 46235717 Attachments: International Residue L imit Status sheet Appendix I - Tolerance Assessment CalculationsAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 22 of 28 

## INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 4 - amino 3,6 - dichloro - 2 - pyridinecarboxylic acid Common Name: Aminopyralid X Proposed tolerance Reevaluated tolerance Other Date: 5/8/09 Codex Status (Maximum Residue Limits) U. S. Tolerances No Codex proposal step 6 or above X No Codex proposal step 6 or above for the crops requested Petition Number: PP#8F74 55 DP#: 360100 Other Identifier: Decision # 401475 Residue definition (step 8/CXL): aminopyralid and its conjugates that can be hydrolysed, expressed as aminopyralid Reviewer/Branch: D. Dotson/C.Swartz/RAB1 Residue definition: Aminopyralid, free and conjugated residues Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm) Corn, forage 0.30 Corn, grain 0.20 Corn, stover 0.20

Limits for Canada Limits for Mexico No Limits X No Limits for the crops requested X No Limits No Limits for the crops requested Residue definition: 4 - amino - 3,6 - dichloro - 2 - pyridinecarboxylic acid (free and conjugated) Residue definition: N/A Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg)

Notes/Special Instructions: S.Funk, 05/13/2009.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 23 of 28 Appe ndix I. Tolerance Assessment Calculations. For the field corn commodities listed below, the Guidance for Setting Pesticide Tolerances Based on Field Trial Data (SOP), along with the tolerance spreadsheet (January 2008 version), was used for calculating r ecommended tolerances. As specified in the SOP, the minimum of the 95% upper confidence limit (UCL) on the 95 th percentile and the point estimate of the 99 th percentile was selected as the tolerance value because the dataset s were large ( 40 samples each ) and reasonably

lognormal. The rounding procedures specified in the SOP were also used. The datasets used to establish tolerances for aminopy ralid on field corn forage, grain, and stover consisted of field trial data representing application rates of 0.03 - 0.034 lb ae/A (single application) with a 60 - to 87 - day PHIfor forage and a 105 - to 138 - day PHIfor grain and stover. The field trial application rates are within 25% of the maximum label application rate; however, the PHI s are much greater than the pro posed PHI s of 0 day s for grain and 8 day s for forage and silage . No residue data were submitted for field corn commodities reflecting the proposed PHI s. The residue values that were entered into the tolerance spreadsheet are provided in Table I - 1. For f orage and stover, 39 out of 40 field trial sample results for aminopy ralid were above the LOQ (LOQ = 0.01 ppm), and for field corn grain, 35 out of 40 field trial results were above the LOQ. Visual inspection of the lognormal probability plot (Figures I - 1 , I - 3, and I - 5) and the results from the approximate Shapiro - Francia test statistic (Figures I - 2, I - 4, and I - 6) indicated that the datasets were reasonably lognormal. Using the tolerance spreadsheet, the recommended tolerances are 0.25 ppm for field cor n forage, 0.15 ppm for field corn grain, and 0.20 ppm for field corn stover. However, for both forage and grain, the recommended tolerances are slightly less than the highest residue value observed in the field trials, of 0.262 ppm and 0.164 ppm, respecti vely . Therefore, HED recommends in favor of tolerances of 0.30 ppm for field corn forage and 0.20 ppm for field corn grain.Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 24 of 28 Table I - 1. Residue data used to calculate tolerance s for residues of aminopyralid on field corn forage,

grain, and stover. Regul ator: EPA EPA EPA Chemical: Aminopyralid Aminopyralid Aminopyralid Crop: Field corn forage Field corn grain Field corn stover PHI: 60 - 87 Days 105 - 138 Days 105 - 138 Days App. Rate: 0.030 - 0.034 lb ae/A 0.030 - 0.034 lb ae/A 0.030 - 0.034 lb ae/A Submitter: D ow AgroSciences Dow AgroSciences Dow AgroSciences MRID Citation: MRID 47572601 MRID 47572601 MRID 47572601 Residues of Aminopyralid (ppm) 0.045 0.015 0.019 0.041 0.026 0.020 0.039 0.043 0.036 0.022 0.021 0.017 0.065 0.052 0.068 0.042 0.030 0 .030 0.113 0.033 0.176 0.057 0.030 0.029 0.012 0.015 0.014 0.119 <0.01 0.091 0.189 0.145 0.167 0.035 0.023 0.064 0.021 0.053 <0.01 <0.01 <0.01 0.012 0.035 0.038 0.060 0.021 0.020 0.028 0.037 0.012 0.021 0.036 <0.01 0.035 0.046 0.0 31 0.033 0.084 0.051 0.071 0.034 0.014 0.018 0.024 0.032 0.030 0.041 0.047 0.034 0.050 0.025 0.012 0.086 0.052 0.108 0.044 0.032 0.021 0.128 0.037 0.131 0.052 0.028 0.037 0.030 0.016 0.029 0.145 0.081 0.075 0.262 0.164 0.107 0.056 0.021 0.060Aminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 25 of 28 Table I - 1. Residue data used to calculate tolerance s for residues of aminopyralid on field corn forage,

grain, and stover. Regul ator: EPA EPA EPA Chemical: Aminopyralid Aminopyralid Aminopyralid Crop: Field corn forage Field corn grain Field corn stover PHI: 60 - 87 Days 105 - 138 Days 105 - 138 Days App. Rate: 0.030 - 0.034 lb ae/A 0.030 - 0.034 lb ae/A 0.030 - 0.034 lb ae/A Submitter: D ow AgroSciences Dow AgroSciences Dow AgroSciences MRID Citation: MRID 47572601 MRID 47572601 MRID 47572601 Residues of Aminopyralid (ppm) 0.016 0.031 0.011 0.012 <0.01 0.011 0.045 0.035 0.046 0.042 0.020 0.046 0.025 0.011 0.025 0.016 <0.01 0.028 0.038 0.036 0.023 0.149 0.056 0.072 Figure I - 1. Lognorm al probability plot of aminopyralid field trial data for field corn forage. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000 0.5000 0.2500 0.1250 0.0625 0.0313 0.0156 0.0078 y = 0.771x - 3.1294 R 2 = 0.9729

PercentilesConcentrations EPA Aminopyralid Field corn forage 60-87 Days 0.030-0.034 lb ae/A Dow AgroSciencesAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 26 of 28 Figure I - 2. Tolerance spreadsheet sum ma ry of aminopyralid field trial data for field corn forage. Regulator: EPA Chemical: Aminopyralid Crop: Field corn forage PHI: 60-87 Days App. Rate: 0.030-0.034 lb ae/A Submitter: Dow AgroSciences

n: 40 min: 0.01 max: 0.26 median: 0.04 average: 0.06 95th Percentile 99th Percentile 99.9th Percentile 0.15 0.20 0.25 (0.20) (0.25) (--) 0.20 0.30 0.50 (0.25) (0.45) (--) 0.15 0.25 0.25 0.9729 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SDAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 27 of 28 Figure I - 3. Lognorm al probability plot of aminopyralid field trial data for field corn grain. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000 0.5000 0.2500 0.1250 0.0625 0.0313 0.0156 0.0078 y = 0.6917x - 3.5939 R 2 = 0.9544

PercentilesConcentrations EPA Aminopyralid Field corn grain 105-138 Days 0.030-0.034 lb ae/A Dow AgroSciences

Figure I - 4. Tolerance spreadshee t sum ma ry of aminopyralid field trial data for field corn grain. Regulator: EPA Chemical: Aminopyralid Crop: Field corn grain PHI: 105-138 Days App. Rate: 0.030-0.034 lb ae/A Submitter: Dow AgroSciences

n: 40 min: 0.01 max: 0.16 median: 0.03 average: 0.04 95th Percentile 99th Percentile 99.9th Percentile 0.09 0.15 0.15 (0.15) (0.15) (--) 0.09 0.15 0.25 (0.15) (0.25) (--) 0.09 0.15 0.15 0.9544 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SDAminopyralid Summary of Analytical Chemistry and Residue Data DP#: 360100

Page 28 of 28 Figure I - 5. Lognorm al probability plot of aminopyralid field trial data for field corn stover. Lognormal Probability Plot

99.9 99 98 95 90 80 70 50 30 20 10 5 2 1 0.1 1.0000 0.5000 0.2500 0.1250 0.0625 0.0313 0.0156 0.0078 y = 0.7799x - 3.3341 R 2 = 0.9762

PercentilesConcentrations EPA Aminopyralid Field corn stover 105-138 Days 0.030-0.034 lb ae/A Dow AgroSciences

Figure I - 6. Tolerance spreadsheet sum ma ry of aminopyralid field trial data for field corn stover. Regulator: EPA Chemical: Aminopyralid Crop: Field corn stover PHI: 105-138 Days App. Rate: 0.030-0.034 lb ae/A Submitter: Dow AgroSciences

n: 40 min: 0.01 max: 0.18 median: 0.03 average: 0.05 95th Percentile 99th Percentile 99.9th Percentile 0.15 0.15 0.20 (0.15) (0.20) (--) 0.15 0.25 0.40 (0.20) (0.35) (--) 0.15 0.20 0.20 0.9762 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SD