UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM Date: 03 NOV 2004 Subject: Ametryn. Residue Chemistry Considerations for Reregistration Eligibility Decision.

DP Barcode: D307104 Case No. 2010 PC Codes: 080801 40 CFR:. § 180.258 From: William H. Donovan, Ph. D., Chemist Reregistration Branch 3 ( RRB3) Health Effects Division ( HED) ( 7509C)

Through: Danette Drew, Branch Senior Scientist RRB3/ HED ( 7509C)

Chemistry Science Advisory Council Health Effects Division ( 7509C)

To: Mark T. Howard, CRM Reregistration Branch 3 Special Review and Registration Division ( 7508C)

This document was originally prepared under contract by Dynamac Corporation ( 1910 Sedwick Rd., Building 100, Durham, NC 27713; submitted 7/ 26/ 2004). The document has been reviewed by the HED and revised to reflect current OPP policies. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 2 Executive Summary Ametryn ( 2 ethylamino) 4( isopropylamino) 6( methylthio) s triazine is a methylthiotriazine herbicide registered for the preemergent control of weeds in bananas, corn, pineapples, plantains, and sugarcane. Ametryn is registered in the U. S. to Syngenta Crop Protection, Inc. under the trade name EVIK ® and is formulated as an 80% water dispersible granule ( DF), which is typically applied as a broadcast preemergence and/ or a directed postemergence application using ground or aerial equipment.

The nature of the residue in plants and animals is adequately understood based on the available corn, sugarcane, banana, goat and hen metabolism studies. In plants, ametryn is extensively metabolized by N dealkylation and desulfation ( oxidation/ hydroxylation) to a variety of triazine ring containing metabolites. The metabolism of ametryn in animals also involves N dealkylation of the isopropyl and ethyl side chains, as well as modification at the 6 position, followed by conjugation, with the triazine ring structure remaining intact. The regulated residues in plant commodities consist of ametryn per se. The residues of concern for tolerance enforcement and risk assessment ( food only) also consist of ametryn per se.

Permanent tolerances are established for residues of ametryn per se in/ on various plant commodities at 0.25 ppm, with the exceptions of corn forage and stover, each at 0.5 ppm, and cassava root at 0.1 ppm [ 40 CFR § 180.258]. There are currently no tolerances for ametryn residues in livestock commodities or for inadvertent residues in rotational crops.

Adequate methods are available for enforcing tolerances and/ or collecting data on ametryn residues in/ on plant and livestock commodities. Two GC methods are available for enforcing tolerances of ametryn in plant commodities and are listed as Methods I and A in PAM Vol. II ( section 180.258). Method I is a GC/ microcoulometric ( MC) detection method for determining ametryn per se, with a limit of quantitation ( LOQ) of 0.05 ppm. Method A is a GC/ flame photometric detection ( sulfur mode, FPD S) method for determining residues of ametryn and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831), with a LOQ of 0.05 ppm for parent and 0.1 ppm for each metabolite.

Considering the data from the available animal metabolism and feeding studies and the calculated maximum theoretical dietary burdens ( MTDBs) of 0.15 0.18 ppm for cattle and 0.04 ppm for poultry and swine, HED concludes that there is no reasonable expectation of quantifiable residues of ametryn occurring in livestock commodities [ 40 CFR § 180.6( a)( 3)]. Therefore, tolerances for livestock commodities are not required at the present time.

Adequate field trial data are available to support the use of ametryn on corn ( field and pop), pineapples, and sugarcane provided the appropriate label amendments are made. An adequate number of tests were conducted in the appropriate geographical regions using the appropriate formulation applied at the maximum use rate. These studies are also supported by adequate storage stability data. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 3 The available processing studies for corn ( 5x rate) and pineapple ( 3x rate) are adequate and indicate that residues of ametryn and its three thiomethyl metabolites are not likely to be quantifiable (

0.02 ppm) in corn and pineapple processed fractions derived from crops treated at the maximum labeled rates. However, the available sugarcane processing study is not adequate because residues were < LOQ in cane ( RAC) following applications at only 1x the maximum rate. A new sugarcane processing study is required.

An adequate confined rotational crop study is available and indicates that the metabolism in rotational crops is similar to the primary crops. Provided that the required label amendments regarding minimum plantback intervals ( PHIs) are made to corn and sugarcane use directions, adequate field rotational crop studies are also available and indicate that rotational crop tolerances are not required.

Residue Chemistry Deficiencies ° The following label amendments for uses on corn and sugarcane should be submitted: ° Corn  remove sweet corn or provide residue data. ° Corn  rotational crop restrictions  minimum PBIs of 3 months for small grains, 10 months for spinach and potatoes, and 11 months for all other crops following application of ametryn to corn. ° Sugarcane  change the maximum application rate to 12 lb ai/ A/ crop cycle from 16 lb ai/ A/ crop cycle, or provide additional crop field trial data to support the 16 lb use rate. ° Sugarcane  rotational crop restriction  restrict rotation to soybean, sorghum, or cotton with a PBI of 11 months following application of ametryn to sugarcane. No rotational crop restriction is needed for corn since it is labeled as a primary crop for ametryn use.

° Unless uses on sweet corn are deleted from all end use products ( EPs), data are required depicting residues of ametryn and its three thiomethyl metabolites in/ on sweet corn ears ( kernels plus cob with husks removed) following treatment at the maximum labeled rate.

° A new sugarcane processing study is required using sugarcane bearing detectable residues or sugarcane from plants treated at 5x the maximum label rate. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 4 N N N N H S C H 3 NH CH 3 CH 3 CH 3 Background Ametryn, ( 2 ethylamino) 4( isopropylamino) 6( methylthio) s triazine, is a selective methylthiotriazine herbicide registered for the control of broadleaf and grass weeds primarily in banana, corn, pineapple, plantains and sugarcane. In the U. S., ametryn is registered to Syngenta Crop Protection, Inc. ( the basic producer) under the trade name EVIK ® and is formulated as a 80% water dispersible granule ( DF). This formulation can be applied as a broadcast preemergence and/ or a directed postemergence application using ground or aerial equipment.

Ametryn is a FIFRA List B pesticide that was the subject of a Phase 4 Review, dated 11/ 19/ 90, and a Reregistration Update, dated 12/ 9/ 94. Tolerances are currently established for the residues of ametryn per se [ 40 CFR § 180.258], and are set at 0.25 ppm for all plant commodities, with the exceptions of corn forage and stover, each at 0.5 ppm, and cassava root at 0.1 ppm. There are currently no livestock tolerances for ametryn. The Ametryn Update recommended that the regulated residues of ametryn should include parent and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831), pending receipt and review of oncogenicity studies for ametryn and hydroxy atrazine. The Ametryn Update also recommended that conclusions regarding the residue of concern should be reevaluated once these toxicity studies are available.

Several data submissions have been received and evaluated since the Ametryn Update ( 12/ 9/ 94). The information contained in this document outlines the current Residue Chemistry Science Assessments with respect to the reregistration of ametryn. The PC Code and nomenclature of ametryn and its thiomethyl metabolites are listed below in Table 1 and the physicochemical properties of ametryn are listed in Table 2.

Table 1. Chemical Structure and Nomenclature for Ametryn and its Thiomethyl Metabolites.

Chemical structure Common name Ametryn Molecular Formula C9H17N5S Molecular Weight 227.35 IUPAC name N2 ethyl N4 isopropyl 6 methylthio 1,3,5 triazine 2,4 diamine CAS name N ethyl N

 ( 1 methylethyl) 6( methylthio) 1,3,5 triazine 2,4 diamine CAS # 834 12 8 PC Code 080801 Ametryn Residue Chemistry Considerations  RED Barcode: D307104 Table 1. Chemical Structure and Nomenclature for Ametryn and its Thiomethyl Metabolites.

5 N N N N H 2 N S CH 3 CH 3 CH 3 N N N N H 2 N S CH 3 CH 3 N N N N H 2 NH 2 S CH 3 Current Food/ Feed Site Registration Banana, Corn, Pineapple, and Sugarcane Chemical structure Common name NA Company experimental name GS 11354; CG 3 IUPAC name NA CAS name N isopropyl 6( methylthio) 1,3,5 triazine 2,4 diamine CAS registry number 4147 57 3 Chemical structure Common name NA Company experimental name GS 11355; CG 4 IUPAC name NA CAS name N ethyl 6( methylthio) 1,3,5 triazine 2,4 diamine CAS registry number 4147 58 4 Chemical structure Common name NA Company experimental name GS 26831; CG 2 IUPAC name NA CAS name 6( methylthio) 1,3,5 triazine 2,4 diamine Ametryn Residue Chemistry Considerations  RED Barcode: D307104 Table 1. Chemical Structure and Nomenclature for Ametryn and its Thiomethyl Metabolites.

6 CAS registry number 5397 01 3 Table 2. Physicochemical Properties of Ametryn Parameter Value Reference Melting point 84.5 86  C MRID 40877301; Ametryn PC RED Chapter pH 8 9 at 20  C ( 1% solution in water)

Density, bulk density, or specific gravity 0.373 g/ mL at 20  C Water solubility 0.020 g/ 100 mL at 20  C Solvent solubility 56.9 g/ 100 mL in acetone 61.4 g/ 100/ mL in methylene chloride 51.6 g/ 100 mL in methanol 46.0 g/ 100 mL in toluene 24.2 g/ 100 mL in n octanol 1.4 g/ 100mL in n hexane Vapor pressure 2.74 x 10 6 mm Hg at 25  C Dissociation constant, pKa 4.02 at 20  C Octanol/ water partition coefficient KOW = 423 ( log P = 2.63)

UV/ visible absorption spectrum Not available RESIDUE CHARACTERIZATION General Discussion on Residue Chemistry of Ametryn 860.1200 Directions for Use Product List A query of HED's OPPIN database conducted on 2/ 10/ 04 identified three end use products ( EPs) for ametryn with feed/ food uses ( Table 3). Only one of these products ( 80% DF) is registered to the Basic producer, Syngenta Crop Protection ( formerly Novartis). The other two labels are an 80% wettable powder ( WP) registered to Marman USA, Inc. and a 4 lb/ gal flowable concentrate ( FlC) registered to Micro Flo Co.

Table 3. Ametryn End use Products ( EPs) with Registered Food/ Feed Uses EPA Reg. No. Formulation Registrant Approved Label Date Product Name 100 786 80% DF Syngenta 3/ 16/ 04 Evik ® DF Herbicide Ametryn Residue Chemistry Considerations  RED Barcode: D307104 Table 3. Ametryn End use Products ( EPs) with Registered Food/ Feed Uses EPA Reg. No. Formulation Registrant Approved Label Date Product Name 7 48273 3 80% WP Marman USA, Inc. 8/ 21/ 01 Ametryne 80W 51036 105 4 lb/ gal FlC Micro Flo Co. 11/ 04/ 96 Ametryne 4FL Herbicide Use Pattern Table A comprehensive summary of the registered food/ feed use patterns of ametryn, as prepared by BEAD, is presented in Appendix 1. A tabular summary of the residue chemistry science assessments for reregistration of ametryn is presented in Table 5. The conclusions listed in Table 5 regarding the reregistration eligibility of ametryn food/ feed uses are based on the use patterns supported by the basic producer, Syngenta Crop Protection. When end use product DCIs are developed, RD should require that all end use product labels ( e. g., MAI labels, SLNs, and products subject to the generic data exemption) be amended such that they are consistent with the basic producer's labels. Based on the available field trial data, the following amendments should be made to all end use products:

° In a letter dated 3/ 15/ 99 with accompanying draft labels, Syngenta indicated that the use on sweet corn was being deleted from the label and the use on corn ( field and pop) was being amended to specify one application per growing season. However, the most recent version of Syngenta's 80% DF label still includes the use on sweet corn and does not include a restriction to one application per season on corn. Uses on sweet corn should be removed from ametryn EP labels, and the use on corn should be restricted to a single application per season.

° As indicated on Syngenta's draft label of 3/ 19/ 99, the total use rate for sugarcane should be restricted to a maximum of 12 lb ai/ A/ crop cycle at all locations. ( Use directions currently allow for up to 16 lb ai/ A/ crop in PR).

° The label should be amended to restrict rotation to either soybean, sorghum, or cotton with a PBI of 11 months following application of ametryn to sugarcane ( see Field Rotational Crop Section). No rotational crop restriction is needed for corn since it is labeled as a primary crop for ametryn use.

° The available rotational crop field trial data will support amending labels to allow minimum rotational crop PBIs of 3 months for small grains, 10 months for spinach and potatoes, and 11 months for all other crops following application of ametryn to corn. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 8 860.1300 Nature of the Residue  Plants 44107901. mem. wpd The qualitative nature of ametryn residues in corn, pineapple, and sugarcane is understood based on the adequate corn, sugarcane, and banana metabolism studies. The currently regulated residues in plant commodities consist of ametryn per se. The Ametryn Update recommended that the regulated residues of ametryn should include parent and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831), pending receipt and review of oncogenicity studies for ametryn and hydroxyatrazine. The Ametryn Update also recommended that conclusions regarding the residue of concern should be reevaluated once these toxicity studies are available.

Hydroxyatrazine has not been classified as to its carcinogenic potential by the HED Cancer Peer Review Committee. The HED Metabolism Committee concluded in a September 29, 1995 meeting that: " For Atrazine, the residues of concern for cancer dietary risk are parent and chloro metabolites". Hydroxyatrazine is not a chlorometabolite and is not considered by the HED Metabolism Committee to possess carcinogenic potential ( HED Doc. No. 014312, R. Hawks, 28 AUG 2000).

The Cancer Assessment Review Committee ( CARC) met to evaluate the carcinogenic potential of ametryn on 21 JUL 2004 and concluded that the " data are inadequate for an assessment of human carcinogenic potential". The carcinogenicity study in rats is unacceptable because the high dose was considered to be excessive. The CARC requested that the carcinogenicity study in rats be repeated at a dose that is adequate to assess carcinogenicity ( Evaluation of the Carcinogenic Potential of Ametryn, J. Kidwell, 02 SEP 2004).

The ametryn risk assessment team has determined that the regulated residues in corn, sugarcane, and pineapple will include parent only for the purpose of tolerance enforcement and risk assessment. The basis for this decision is as follows:

° Residue levels of ametryn and its three thiomethyl metabolites are very low in the edible parts of crops that will be treated with ametryn.

 In corn grain, residue levels of ametryn and its three thiomethyl metabolites were each < 0.02 ppm ( LOQ) in 29 field trials conducted at 1x, 9 trials at 2x, 4 trials at 3x, and 4 trials at 5x.

 In pineapple, residue levels of the three thiomethyl metabolites were each < 0.02 ppm ( LOQ) in 8 field trials conducted at 1x, 3 trials at 2x, and 2 trials at 3x. One 1x treated pineapple sample was reported to contain 0.05 ppm ametryn.

 In sugarcane, residue levels of ametryn and its three thiomethyl metabolites were each < 0.02 ppm ( LOQ) in 17 field trials conducted at a nominal rate of 1x. ° Corn, sugarcane, and banana metabolism studies show that the thiomethyl metabolites each comprise < 10% TRR in the edible parts of the crops studied. ° The toxicological database does not indicate a special concern regarding the toxicity of three thiomethyl metabolites. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 9 In the corn metabolism study, [ U 14C triazine] ametryn was applied postemergence as a basal/ soil directed spray to greenhouse grown corn at 4 lb ai/ A ( 2x the maximum label rate) when plants were 12 18 inches in height. Total radioactive residues ( TRR) were 2.47 ppm in forage at 56 days after treatment ( DAT), and 4.56 ppm in fodder and 0.16 ppm in grain at maturity ( 111 DAT). Organosoluble 14C residues in immature forage declined from 100% of the TRR on the day of application to 11% of the TRR in mature fodder. Radioactive residues in immature forage were not further analyzed. At maturity, organosoluble residues in fodder consisted principally of ametryn ( 1.8% TRR) and GS 11354 ( 0.2% TRR). In mature tissues, the majority of 14C residues consisted of aqueous soluble ( 45 58% TRR) and insoluble ( 31 57% TRR) residues. Cation exchange chromatography separated aqueous soluble 14C residues from mature tissues into numerous distinct components each of which accounted for < 10% of the TRR, with the exception of P3 fractions from stalks and cobs. The cation exchange elution profiles were qualitatively similar for 14C residues from stalks, cobs, and grain. Aqueous soluble 14C residues ( 60.5% TRR) in stalks with foliage were separated by cation exchange chromatography into 14 distinct components, with each one accounting for 0.7 12.7% of the TRR. HPLC and 2D TLC analyses of the isolated fractions identified the metabolites GS 17792 ( 1.8% TRR) and GS 17794 ( 3.6% TRR). Insoluble 14C residues in stalks/ foliage were solubilized by refluxing in aqueous MeOH and by enzymatic and acid hydrolyses, and were polar in nature.

In the sugarcane metabolism study, [ U 14C triazine] ametryn was applied to greenhouse grown sugarcane as a preemergence application at 8 lb ai/ A and again as soil/ basal directed sprays at 4 lb ai/ A/ application at 29 and 50 days after planting, for a total of 16 lb ai/ A ( 1x maximum use rate). TRR in forage were 0.12 and 1.57 ppm in forage collected 29 and 50 days after the first application. In separated stalks and foliage, TRR were 0.40 and 2.17 ppm, respectively, at 84 DAT and 0.42 and 3.06 ppm at 202 DAT. Organosoluble 14C residues in immature sugarcane declined from 55.2% of the TRR on Day 29 to 28 32% of the TRR in Day 84 stalks and foliage and 3.4 7.2% of the TRR in mature ( Day 202) stalks and foliage. Organosoluble residues were not further analyzed. Cation exchange chromatography separated aqueous soluble 14C residues from mature tissues into 14 distinct components. Each of these fractions accounted for < 10% of the TRR, with the exception of one fraction ( 12.6% TRR) in foliage. Insoluble 14C residues from mature tissues were released by refluxing in aqueous MeOH and by enzymatic and acid hydrolyses.

In the banana metabolism study, [ U 14C triazine] ametryn was applied three times as a directed soil application to greenhouse grown banana plants at 112 120 days retreatment intervals, beginning when plants were 3.5 feet in height. TRR were 0.579 in immature leaves collected 31 days after the second application and 1.59 ppm in mature leaves collected at fruit maturity, 69 days after the second application. TRR in mature fruit ( 0.087 ppm) were substantially lower than in leaves and were equally distributed between the peel ( 0.098 ppm) and pulp ( 0.076 ppm). Methanolic extraction of leaf and fruit samples released 61.4 90.9% of the TRR, and subsequent analyses of organic and aqueous soluble 14C residues identified 40.6 61.6% of the TRR in leaves and 58.7 75.6% of the TRR in whole fruit, peel and pulp samples. Including ametryn, a total of 10 triazine ring containing compounds were identified in leaves and fruit. In mature leaves, ametryn was detected at 3.0% of the TRR and the major metabolite was GS 11957 ( 39.7% TRR); the Ametryn Residue Chemistry Considerations  RED Barcode: D307104 10 remaining 8 metabolites each accounted for  5.1% of the TRR and included: GS 11354, GS 26831, G 34048, GS 17791, GS 17792, GS 17794, G 28521, and GS 12517. In whole fruit, peel and pulp, the major 14C residues were GS 11957 ( 39.3 56.7% TRR) and G 28521 ( 15.1 17.2% TRR); the remaining 4 metabolites each accounted for  3.3% of the TRR and included: G 34048, GS 17791, GS 17792, and GS 17794.

A separate acid hydrolysis released 87 96.1% of the TRR from leaves and fruit fractions, and subsequent analyses identified 6 7 triazine ring containing metabolites, accounting for 72.9 79.2% of the TRR. The major acid hydrolyzed 14C residues in mature leaves were G 28521 ( 18.2% TRR), GS 17794 ( 14.8% TRR), G 34048 ( 12.1% TRR), and GS 11957 ( 30.4% TRR). The major acid hydrolyzed residues in whole fruit and pulp were G 28521 ( 40.7 49.0% TRR) and GS 11957 ( 19.7 23.8% TRR).

Based on the banana metabolism study, for which the most extensive data were available, ametryn is extensively metabolized in plants primarily by N dealkylation and desulfation ( oxidation/ hydroxylation) to a variety of triazine ring containing metabolites. At least in bananas, glutathione conjugation did not appear to be an important route of metabolism.

860.1300 Nature of the Residue  Livestock The qualitative nature of ametryn residues in poultry and ruminants is understood based on the adequate goat and hen metabolism studies. There are currently no tolerances for ametryn residues in livestock commodities, and the available metabolism and feeding studies indicate that none are presently required.

The ametryn risk assessment team has determined that, if new ametryn uses are added so that tolerances are needed for livestock commodities, the regulated residues in livestock commodities should include parent and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831) for the purpose of tolerance reassessment and risk assessment. The basis for this decision is as follows:

° Metabolism studies in goats and hens demonstrate that ametryn and the thiomethyl metabolites comprise > 10% TRR in several edible livestock matrices. ° An adequate data collection method is available ( Method AG 649) for determination of ametryn and its three thiomethyl metabolites. If necessary, this method could be validated for tolerance enforcement purposes.

In the goat metabolism study, two goats were dosed orally for 3 days with [ U 14C triazine] ametryn at a level equivalent to 50 ppm in the diet, which is  280x the maximum theoretical dietary burden ( MTDB) for dairy cattle. Maximum 14C residues were attained in milk on Day 2 at 0.686 or 1.277 ppm. At sacrifice, TRR were 2.71 2.89 ppm in liver, 3.0 3.05 ppm in kidney, 0.092 0.137 ppm in muscle, and 0.084 0.088 ppm in fat. Solvent extraction released 84% of the TRR from fat, 42 53% of the TRR from milk, muscle, and kidney, and 29% of the TRR from Ametryn Residue Chemistry Considerations  RED Barcode: D307104 11 liver. Subsequent acid hydrolyses released the remaining radioactivity from each matrix, and HPLC and TLC analyses identified > 80% of the TRR in each matrix.

The principal organosoluble residues in goats milk and tissues were ametryn, GS 11354, and GS 26831. Ametryn accounted for 40% of the TRR in fat, 9.7% TRR in muscle, and 0.2 2.3% TRR in liver, kidney, and milk, and GS 11354 accounted for 20.8% TRR in fat, 11.5% TRR in muscle, and 1.9 2.4% TRR in liver, kidney, and milk. Metabolite GS 26831 accounted for 13.5% TRR in muscle, 7.0 9.6% TRR in milk and kidney, and 3.3 4.7% TRR in liver and fat. The organosoluble metabolite GS 11355 was also identified in milk and all tissues at 0.9 4.6% of the TRR. The combine residues of ametryn its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831) accounted for 16.4% TRR in milk, 9.1% TRR in liver, 12.5% TRR in kidney, 37.1% TRR in muscle, and 71.2% TRR in fat; actual levels of these combined residues ranged from 0.03 ppm in muscle to 0.37 ppm in kidney. Other minor solvent extracted metabolites containing the triazine ring included: GS 11794, GS 11957, G 4048, BPM VI 31P, GS 17791, and GS 17792; each of these metabolites were detected in various tissues or milk at 0.3 9.8% TRR. The 14C residues released by acid hydrolysis were attributed to 2,6 dihydroxy 4 amino triazine ( G 35713) at 61% TRR 78% TRR in liver, 47 58% TRR in milk, muscle, and kidney, and 16% TRR in fat.

In the poultry metabolism study, 10 hens were dosed orally for 3 days with [ U 14C triazine] ametryn at levels equivalent to 50 ppm in the diet ( 1,250x MTDB). Maximum 14C residues in eggs were attained on Day 3 at 0.099 ppm in egg whites and 0.268 ppm in egg yolks. At sacrifice, TRR were 4.98 ppm in liver, 0.379 0.558 in muscle, 0.618 ppm in skin, and 0.240 ppm in fat. Solvent extraction released 72 and 58% of the TRR from egg whites and fat, respectively, and 16 25% of the TRR from the remaining matrices. Subsequent protease and acid hydrolyses released essentially all of the remaining radioactivity from each matrix.

The principal organosoluble residues in poultry were ametryn, accounting for 40% of the TRR in fat and 0.3 2.7% of the TRR in skin, yolks, and muscle, and GS 26831, accounting for 52% TRR in egg whites, 10.4% TRR in yolks, 5.7 8.7% TRR in muscle, and 1.2 1.6% TRR in fat and liver. Other minor organosoluble residues in eggs and tissues included GS 11355 ( 0.06 5.2% TRR), GS 11354 ( 0.1 3.0% TRR), G 34048 ( 0.2 0.4% TRR), and a sulfoxide metabolite ( 0.4% TRR). The combine residues of ametryn its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831) accounted for 63.7% TRR in egg white, 14.3% TRR in yolks, 14 24% TRR in muscle, 51.7% TRR in fat, and 7.4% TRR in liver; actual levels of the combined residues ranged from 0.03 ppm in yolks to 0.42 ppm in liver. Acid hydrolysis of the residual solids released the following triazine ring containing metabolites: G 35713 at 61% TRR in egg yolks and 21 36% TRR in liver, muscle, skin, and fat; G 28521 at 17 18% TRR in liver, muscle, and skin; and GS 17792 at 9.4 21% TRR in liver, muscle, and skin.

The metabolism of ametryn in livestock involves N dealkylation of the isopropyl and ethyl side chains, as well as modification at the 6 position, followed by conjugation, possibly to proteins, with the triazine ring structure remaining intact. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 12 860.1340 Residue Analytical Methods  Plants Tolerance enforcement methods: Two methods are available for enforcing tolerances of ametryn in plant commodities and are listed as Method I and A in PAM Vol. II. Method I is a GC/ microcoulometric ( MC) detection method for determining ametryn per se, and Method A is a GC/ FPD S method for determining residues of ametryn and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831).

For Method I ( Method AG 63), residues are extracted from plant commodities with acetonitrile, diluted with water, and partitioned into methylene chloride. Residues are then cleaned up using an alumina column and analyzed by GC / MC. The LOQ for ametryn is 0.05 ppm.

For Method A ( Method AG 169), residues are extracted with chloroform and concentrated. For analysis of ametryn, extracted residues are redissolved in carbon tetrachloride and cleaned up using a sodium bisulfate column. For analysis of the metabolites, extracted residues are dissolved in 0.5 N HCl and partitioned against hexane. The aqueous fraction is made basic and metabolite residues are then partitioned into methylene chloride. Parent and metabolite residues are then determined by GC/ FPD S. The LOQ is 0.05 ppm for parent and 0.1 ppm for each metabolite.

In addition to the above methods, a more recent GC/ FPD S method ( Method AG 563) is available. This method, which has been used extensively for data collection, has undergone a successful independent laboratory method validation trial and has been validated using 14C labeled samples from the corn and sugarcane metabolism studies.

For Method AG 563, residues of ametryn and its thiomethyl metabolites are extracted by refluxing in methanol/ water ( 9: 1, v/ v) for 1 hour, concentrated to an aqueous solution, acidified, and partitioned against hexane. Residues in the aqueous solution are then made alkaline ( pH ~ 10) and cleaned up using a Chem Elute extraction column eluted with methylene chloride. Residues are concentrated and determined by GC/ FPD S. The LOQ for each of the four analytes is 0.02 ppm.

Data collection methods: Residue data from the acceptable field trials and processing studies have been collected using the adequate Method AG 563, described above, and a related GC/ FPDS method ( Method AG 581) that was used for the analysis of residues in soapstock. For Method AG 581, soapstock is dissolved in water, acidified, filtered, and extracted with hexane. Residues in the remaining aqueous phase are then made alkaline and cleaned up using a Chem Elut extraction column eluted with methylene chloride. Residues are concentrated and determined by GC/ FPD S. The LOQ for Method AG 581 is 0.05 ppm for each analyte. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 13 860.1340 Residue Analytical Methods  Livestock commodities 44477701. mem. wpd 44477702. mem. wpd Tolerance enforcement method: As tolerances are not currently necessary for livestock commodities, an enforcement method is not required.

Data collection method: An adequate GC/ NPD method ( Method AG 649) is available for determining residues of ametryn and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831) in livestock commodities. For this method, residues are extracted with methanol/ water ( tissues and egg) or acetone/ water ( milk), filtered, and concentrated. Residues are then cleaned up using a C 18 solid phase extraction cartridge and a Florisil column. Residues are determined by GC/ NPD with all four analytes determined in a single injection, and residues are express in terms of each analyte. The LOQ for ametryn and each metabolite is 0.02 ppm in tissues and eggs and 0.01 ppm in milk. The above method was successfully validated by the developing laboratory and was radiovalidated using milk, liver, and kidney samples from an 14C ametryn dosed dairy goat.

860.1360 Multiresidue Methods The FDA PESTDATA database dated 11/ 01 ( PAM Volume I, Appendix I) indicates that ametryn per se is completely recovered using Multiresidue Methods Section 302. The Ametryn Update also indicated that additional data have been submitted examining the recovery of ametryn and its thiomethyl metabolites and hydroxy triazine methods through the Multiresidue Method Testing Protocols.

860.1380 Storage Stability 43931001. mem. wpd In support of previously submitted goat and poultry metabolism studies, Syngenta Crop Protection, Inc. submitted data supporting the stability of 14C residues in sample matrices over the course of these metabolism studies. In the goat study, samples were initially analyzed within 3 months of sampling, and reanalyzed toward the end of the study after  18 months of frozen storage. In the poultry study, samples were initially analyzed within 5 months of sampling, and reanalyzed toward the end of the study after  17 months of frozen storage. The supporting storage stability data indicate that the extractability of 14C residues and the distribution of radioactivity between solvent fractions was similar for each sample matrix at the different storage intervals. In addition, the chromatographic profile of selected solvent fractions was similar for the two analyses indicating that 14C residues were stable in frozen storage over the course of these studies.

44783701. mem. wpd Ametryn Residue Chemistry Considerations  RED Barcode: D307104 14 The available storage stability data for plant RACs and processed commodities are adequate and indicate that ametryn and its three thiomethyl metabolites are stable at  20  C for at least 30 months in sugarcane and corn grain, 28 months in corn oil, 20 24 months in corn forage, 25 months in bananas, and 22 months in pineapples, sugarcane molasses and sugar, and corn meal, grits, flour, and starch. These data support the sample storage intervals in the field trials for primary and rotational crops and the processing studies.

44477704. mem. wpd The available interim storage stability data on livestock commodities indicate that residues of ametryn and its thiomethyl metabolites are completely stable at  20  C in eggs and milk for at least 14 months. The three thiomethyl metabolites are also relatively stable in frozen muscle, with only a 15% decline occurring after 14 months of storage. Ametryn appears to be less stable in muscle, declining by 28% after 14 months. Residues of ametryn and all three metabolites declined steadily in liver. By the 14 month sampling interval, residues of ametryn and its thiomethyl metabolites had declined by 20 34% in frozen liver. The current data reported in the interim study adequately support the cattle feeding study, in which samples of milk and tissues analyzed after  10 12 months of storage, but do not cover the maximum sample storage interval in the poultry feeding study, in which egg and tissue samples were stored for 18 20 months prior to analysis.

Conclusions The reregistration requirements for storage stability data are fulfilled for plant and livestock commodities. HED notes that the interim storage stability data on poultry commodities covers storage intervals up to 14 months while samples from the livestock feeding studies were stored frozen for up to 20 months. However, HED will not require additional storage stability data for poultry at this time for the following reasons: 1) submitted data demonstrate stability in eggs and milk for at least 14 months, and 2) the low poultry dietary burden and low transfer rate of residues to poultry tissues results in no reasonable expectation of finite residues in poultry tissues [ 40 CFR 180.6( a)( 3)]. This conclusion should be reevaluated if any new ametryn uses are added that result in an increase in the dietary burden to poultry.

860.1400 Water, Fish, and Irrigated Crops Ametryn is not registered for direct use on water and aquatic food and feed crops; therefore, no residue chemistry data are required under these guideline topics.

860.1460 Food Handling Ametryn is not registered for use in food handling establishments; therefore, no residue chemistry data are required under this guideline topic.

860.1480 Meat, Milk, Poultry, and Eggs 44477705. mem. wpd 44477706. mem. wpd Ametryn Residue Chemistry Considerations  RED Barcode: D307104 15 Based on the use of ametryn on corn and pineapples, there is the potential for exposure of livestock to ametryn residues in livestock feed items. The maximum theoretical dietary burdens ( MTDB) of ametryn residues for livestock are calculated below in Table 4 considering the regulation of ametryn per se. Based on reassessed tolerances for ametryn per se, the MTDB is 0.15 and 0.18 ppm for beef and dairy cattle, respectively, and the MTDB for both poultry and swine is 0.04 ppm.

Table 4. Calculation of Maximum Theoretical Dietary Burdens of Livestock for Ametryn. 1 Feed Commodity % Dry Matter1 % Diet2 Reassessed Tolerance ( ppm) Dietary Contribution ( ppm) 3 ametryn residues ametryn residues Beef and Dairy Cattle Corn, forage 40 40/ 50 0.10 0.100/ 0.125 Corn, grain 88 20 0.05 0.011 Pineapple, process residue 4 25 20 0.05 0.040 TOTAL BURDEN 0.15/ 0.18 5 Poultry and Swine Corn grain NA 80 0.05 0.040 TOTAL BURDEN 0.040 1 The MTBD was calculated based on residues of ametryn per se. 2 Table 1 ( OPPTS Guideline 860.1000). 3 Contribution = ([ tolerance /% DM] X % diet) for beef and dairy cattle; Contribution = ( tolerance X % diet) for poultry and swine. 4 The tolerance value for pineapple was used for residues in pineapple processing waste. 5 MTDB for beef/ dairy cattle respectively.

In an adequate ruminant feeding study, three groups of dairy cattle ( 3 cows/ group) were dosed orally via capsules once a day for 28 30 consecutive days with ametryn ( 97.2% ai) at levels equivalent to 2.15, 6.20, and 20.1 ppm in the feed. These dose levels are equivalent to 12x, 34x and 112x the MTBD for dairy cattle. Milk samples were collected on Study Days 1, 3, 7, 14, 21, and 26, and samples of blood, liver, kidneys, muscle, and fat were collected within 24 hours of the final dose. All samples were stored frozen ( ca.  20  C) for up ~ 12 months prior to analysis, an interval that is supported by the available storage stability data.

Milk and tissue samples were analyzed for residues of ametryn and its three thiomethyl metabolites ( GS 11354, GS 11355, and GS 26831) using an adequate GC/ NPD method ( AG 649). The validated LOQ for ametryn and each metabolite is 0.02 ppm in tissues and 0.01 ppm in milk, for combined LOQs of 0.08 and 0.04 ppm, respectively.

All samples of milk and tissues were analyzed from the 20.1 ppm dose group ( 112x), but only milk ( day 26) and muscle were analyzed from the 2.15 and 6.2 ppm dose groups ( 12x and 34x). Residues of each analyte were < 0.01 ppm (< LOQ) in all milk samples from cows dosed at 20.1 ppm, for combined residues of < 0.04 ppm, and residues were also < 0.01 ppm for each analyte in the selected milk samples from the 2.15 and 6.2 ppm dose groups. In tissues, residues of each Ametryn Residue Chemistry Considerations  RED Barcode: D307104 16 analyte were < 0.02 ppm (< LOQ) in blood, liver, kidney, muscle, and fat from each cow in the 20.1 ppm dose group, for combined residues of < 0.08 ppm in each matrix.

Based on the results of the ruminant metabolism and feeding study, HED concludes that there is no reasonable expectation of finite residues occurring in milk and tissues of cattle, goats, hogs, horses, and sheep [ 40 CFR § 180.6( a)( 3)]. Therefore, tolerances for ametryn residues in livestock commodities are not required to support the current use pattern.

In the poultry feeding study, three groups of laying hens ( 15 hens/ group) were fed ad libitum for 28 consecutive days with feed containing ametryn at nominal levels of 0.5, 1.5, and 5.0 ppm, which are equivalent to 12.5x, 38x, and 125x the MTDB. Egg samples were collected on Study Days 0 ( pre dose), 1, 3, 7, 14, 21, and 28 and composited by subgroup. Hens were sacrificed 44 48 hours following removal from treated feed and samples of liver, muscle ( composite of breast and leg), skin ( including attached fat) and fat ( peritoneal) were collected and composited by subgroup. All samples were stored frozen until analysis. The maximum frozen ( ca.  15  C) storage interval was 20 months for eggs and tissues and is not supported by the available storage stability data, which assessed residue stability up to only 14 months. However, because the poultry dietary burden is so low, HED will not require the registrant to submit addition storage stability data to cover the extra six months of storage time. Samples were analyzed for residues of ametryn and its thiomethyl metabolites using an adequate GC/ NPD method ( AG 649), which has a validated LOQ of 0.02 ppm for each analyte in eggs and tissues.

All collected egg and tissue samples from the 5 ppm dose group were analyzed, but only liver, muscle, and Day 7 egg samples were analyzed from the 0.5 and 1.5 ppm dose groups because residues in the high dose group were < LOQ. Residues of ametryn and each metabolites were < 0.02 ppm (< LOQ) in all analyzed samples of whole eggs from each group, for combined residues of < 0.08 ppm. Residues of ametryn and each metabolite were also < 0.02 ppm (< LOQ), in all tissues samples from the 5 ppm dose group, and in the analyzed muscle and liver samples from the 0.5 and 1.5 ppm dose groups. Combined residues were < 0.08 ppm in each tissue sample.

Information from the feeding study together with the adequate poultry metabolism study are sufficient to assess the need for tolerances in poultry commodities based on the current use pattern.

The available residue data on eggs from the feeding study indicate that quantifiable residues are unlikely to occur in eggs as residues of ametryn and the thiomethyl metabolites were each < LOQ for the at 5 ppm dose group ( 125x). The egg samples were collected at the appropriate intervals, and although samples were stored frozen for 19 20 months, the available storage stability data indicate that residues in frozen eggs are completely stable for at least 14 months, with recoveries of > 100%. Therefore, substantial declines would not be expected by 20 months.

In addition, in the poultry metabolism study conducted for 3 days at 1,250x the MTDB, the combined residues of ametryn and its three thiomethyl metabolites in eggs and tissues ranged from Ametryn Residue Chemistry Considerations  RED Barcode: D307104 17 0.03 ppm in yolks to 0.42 ppm in liver. If residues are adjusted to a 100x dose level, then the range of expected combined residues would be 0.002 0.033 ppm, which are below the combined LOQ of 0.08 ppm for the analytical method. Considering the current dietary exposure of poultry and the above data, HED concludes that there is no reasonable expectation of finite residues occurring in poultry commodities [ 40 CFR § 180.6( a)( 3)], and an additional poultry feeding study is not required are the present time.

860.1500 Crop Field Trials The reregistration requirements for magnitude of the residue in plants are fulfilled for field corn, pineapple, and sugarcane. An adequate number of tests were conducted on these crops in the appropriate geographical regions at the maximum labeled use rates. Results from these field trials are summarized below. Field trial data are also available on bananas; however, uses on bananas and plantains have been deleted from the most recent version of the Syngenta's label for the 80% DF ( EPA Reg No. 100 786, dated 3/ 30/ 04). The available data for field corn will also support the use on pop corn, and the field corn forage and stover data can be used to cover residues in/ on sweet corn forage and stover. However, data are required depicting residues of ametryn and its three thiomethyl metabolites in/ on sweet corn ears ( kernels plus cob with husks removed) if the use on sweet corn is to be maintained. Although Syngenta indicated in 1999 that the use on sweet corn was being deleted from its label ( MRID 44783700), the most recent label for the 80% DF still includes use directions for sweet corn.

Field Corn. Adequate data are available from a total of 28 tests conducted on field corn throughout the U. S. Ametryn ( 80% WP) was applied using ground equipment as a single postemergence directed spray at 2 lb ai/ A ( 1x) in 15 tests, 4 lb ai/ A ( 2x) in 9 tests, 6 lb ai/ A ( 3x) in 2 tests, and 10 lb ai/ A ( 5x) in 2 tests. Samples of forage and silage stage forage were collected from each test at 28 36 DAT and 42 85 DAT, respectively; and samples of grain and fodder were collected at maturity ( 80 126 DAT). The label currently specifies 30 day PHI for forage and prohibits applications within 3 weeks of tasseling.

For the tests conducted at 1x, residues of ametryn were < 0.02 0.10 ppm in/ on forage ( n= 30), < 0.02 0.08 ppm in/ on silage stage forage ( n= 30), and < 0.02 ppm in/ on fodder ( n= 30). Residues of GS 11354 were < 0.02 0.04, < 0.02 0.05, and < 0.02 0.03 ppm in the 1x forage, silage stage forage, and fodder samples, respectively. Residues of GS 11355 were < 0.02 0.04 ppm in the 1x forage, silage stage forage, and fodder samples. Residues of GS 26831 were < 0.02 0.02 ppm in the 1x forage samples, and were < 0.02 ppm in the 1x silage stage forage and fodder samples. Maximum combined residues were 0.20 ppm in/ on forage and < 0.11 ppm in/ on fodder. Residues of ametryn, GS 11354, and GS 26831 were each < 0.02 ppm in all 1x treated grain samples ( n= 29). Residues of GS 11355 were also < 0.02 ppm in all treated samples except in two samples from one test with residues at 0.03 and 0.04 ppm.

For the exaggerated rate tests, residue analyses were performed on a total of 51 samples of forage, silage stage forage, and fodder treated at 2x ( 9 samples per matrix), 3x ( 4 samples per matrix), and 5x ( 4 samples per matrix). Residues were  0.16 ppm for ametryn and residues of Ametryn Residue Chemistry Considerations  RED Barcode: D307104 18 GS 11354, GS 11355, GS 26831 were each < 0.02 0.04 ppm in/ on forage, silage stage forage, and fodder samples from the 2x, 3x, and 5x tests. Residues of ametryn and each metabolite were < 0.02 ppm in/ on all grains samples from the exaggerated rate trials ( 2x, 9 samples; 3x, 4 samples; and 5x, 4 samples).

Pineapple. Adequate residue data are available from a total of 13 tests conducted in HI on pineapple. Ametryn ( 80% WP) was applied as a single broadcast application to the planting or ratoon pineapple crop at rates of 7.2 lb ai/ A ( 1x) in 8 tests, 14.4 lb ai/ A ( 2x) in 3 tests, and 21.6 lb ai/ A ( 3x) in 2 tests. Samples of pineapple were harvested at 142 161 days after treatment; the labeled PHI is 160 days. Residues of ametryn were < 0.02 0.05 ppm and residues of GS 11354, GS 11355, and GS 26831 were each < 0.02 ppm in/ on 16 samples of pineapples from the 1x application; combined residues were < 0.08< 0.11 ppm. Residues of ametryn and each metabolite were < 0.02 ppm in/ on the 6 treated samples from the 2x trials and the 4 treated samples from the 3x trials.

Sugarcane. Residue data reflecting a variety of application rates and timings for ametryn ( 80% WP) are available from 17 tests conducted on sugarcane. In nine of the tests conducted in FL( 1), HI( 4), LA( 2), and PR( 2), ametryn was applied as a combination of one preemergence broadcast application at 5.6 lb ai/ A and two postemergence broadcast applications at 2.4 and 4 lb ai/ A for a total of 12 lb ai/ A/ crop. In two other tests conducted in FL, ametryn was applied as three directed postemergence applications at 1.2 lb ai/ A/ application for a total of 3.6 lb ai/ A/ crop. In three more tests conducted in TX, ametryn was applied as one preemergence and one postemergence broadcast application at 2.4 lb ai/ A/ application for a total of 4.8 lb ai/ A/ crop. In two other tests in LA, ametryn was applied as one broadcast and one directed postemergence application at 2.5 lb ai/ A/ application for a total of 5 lb ai/ A/ crop. In one exaggerated rate test in HI, ametryn was applied as three broadcast applications, one preemergence and two postemergence at 11.2, 4.8, and 8 lb ai/ A, for a total of 24 lb ai/ A/ crop. In each test, the final postemergence application was made prior to close in.

Samples of mature sugarcane were harvested 143 300 days following the final treatment. Residues of ametryn, GS 11354, GS 11355, and GS 26831 were each < 0.02 ppm in all 33 treated samples of sugarcane ( without leaves), for combined residues of < 0.08 ppm.

The current use directions for ametryn on sugarcane generally allow for a preemergence and two postemergence broadcast or directed applications, with the last application being made prior to close in. Use rates vary considerably depending on location. Maximum rates allowed per sugarcane crop are as follows: FL  3.6 lb ai/ A; HI  12 lb ai/ A; LA  6.8 lb ai/ A; PR  16 lb ai/ A; and TX  6 lb ai/ A. Provided the maximum use rate per crop cycle is restricted to a maximum of 12 lb ai/ A at all locations, then the available residue data for sugarcane are adequate. Syngenta previously indicated in a letter ( MRID 44783700) that the maximum use rate in PR would be reduced to 12 lb ai/ A; however, the current label still bears the higher use rate ( 16 lb ai/ A) for PR.

Banana. Although Syngenta is no longer supporting the use of ametryn on bananas and plantains, adequate residue data are available from 8 tests conducted in HI( 4) and PR( 4). In each Ametryn Residue Chemistry Considerations  RED Barcode: D307104 19 test, ametryn ( 80% WP) was applied to bananas as three soil directed applications at  30 day intervals using ground equipment. Ametryn was applied at 3.2 lb ai/ A/ application in six of the tests, for a total of 9.6 lb ai/ A/ crop, and at 6.4 lb ai/ A/ application in the other two tests, for a total of 19.2 lb ai/ A. Banana samples were harvested 6 7 days following the last application in each test, and subsamples were separated into peel and pulp.

Following three applications totaling 9.6 lb ai/ A/ crop, residues in/ on 11 treated whole banana samples were < 0.02 0.04 ppm for ametryn and < 0.02 ppm each for GS 11354, GS 11355, and GS 26831, for combined residues of < 0.08< 0.12 ppm. Residues of ametryn and the three metabolites were each < 0.02 ppm in 11 banana pulp samples, for combined residues of < 0.08 ppm. Following three applications totaling 19.2 lb ai/ A/ crop, residues in/ on 3 treated whole banana samples were < 0.02 0.17 ppm for ametryn, < 0.02 0.04 ppm for GS 11354, and < 0.02 ppm each for GS 11355 and GS 26831, for combined residues of < 0.08< 0.25 ppm. In the 3 associated pulp samples, residues were < 0.02 ppm each for ametryn and the three metabolites, for combined residues of < 0.08 ppm.

The available banana residue data would support the use of up to three directed applications of ametryn ( WP, FLC or DF) to bananas or plantains at 3.2 lb ai/ A/ application at 30 day intervals, using ground equipment, for a maximum use rate of 9.6 lb ai/ A/ crop cycle with a 7 day PHI.

860.1520 Processed Food and Feed The reregistration requirements for magnitude of the residue in processed food/ feed are satisfied for corn and pineapple, but not sugarcane. The available processing data for corn ( 5x rate) and pineapple ( 3x rate) indicate that residues of ametryn and its three thiomethyl metabolites are not likely to be quantifiable (

0.02 ppm) in corn and pineapple processed fractions derived from crops treated at the maximum labeled rates. However, the available sugarcane processing study is not adequate because residues were < LOQ in cane ( RAC) following applications at only 1x the maximum rate.

Corn. In three tests conducted in IL, ametryn ( 80% WP) was applied to field corn as a single postemergence, directed spray at either 2 lb ai/ A ( 1x), 6 lb ai/ A ( 3x), or 10 lb ai/ A ( 5x). Bulk corn grain samples was harvested from each test at maturity, 116 days post treatment, and processed using simulated dry and wet milling procedures into the following fractions: large grits, small grits, meal, flour, starch, crude oil and refined oil.

Residues of ametryn, GS 11354, and GS 26831 were each < 0.02 ppm in all samples of corn grain and processed fractions from each test. Residues of GS 11355 were also < 0.02 ppm in all processed fractions with the exception of small grits ( 0.02 ppm in the 3x and 5x samples) and wet milled crude oil ( 0.02 ppm in the 3x and 5x samples) and refined oil ( 0.03 ppm in the 1x sample). However, the detectable residues were reported to be the result of an interfering peak, and reanalysis of small grits and crude oil using GC/ MS indicated that residues of ametryn and the three thiomethyl metabolites were each < 0.01 ppm in these fractions. As residues of each analyte Ametryn Residue Chemistry Considerations  RED Barcode: D307104 20 were < LOQ in all processed fractions and corn grain from plants treated at 5x the maximum label rate, no additional corn grain processing data are required.

Pineapple. In four tests conducted in HI, ametryn ( 80% WP) was applied to pineapples as a single broadcast application at either 7.2 lb ai/ A ( 1x, 2 tests) or 21.6 lb ai/ A ( 3x, 2 tests). Mature pineapple fruits were harvested at 151 161 days post treatment and processed using simulated commercial procedures into bran, pulp, slices, and juice.

Residues of ametryn and the three metabolites were each < 0.02 ppm (< LOQ) in/ on whole pineapples treated at 1x or 3x, and were < 0.02 ppm in juice, pulp, and slices, and < 0.1 ppm (< LOQ) in bran processed from 1x and 3x treated fruits. Although pineapples were not treated at the maximum theoretical concentration factor of 3.8x, HED concludes that the 3x treatment rate was sufficient considering the long interval between application and harvest of fruit. Therefore the pineapple processing study is adequate and indicates that residues are unlikely to concentrate in pineapple processed fractions.

Sugarcane. In two tests conducted in LA, ametryn ( 80% WP) was applied to sugarcane as either one broadcast and one directed postemergence application at 2.5 lb ai/ A/ application ( 5 lb ai/ A/ crop; 0.4x), or as a preemergence broadcast application at 5.6 lb ai/ A and two postemergence broadcast applications at 2.4 and 4 lb ai/ A ( 12 lb ai/ A/ crop; 1x). Mature canes were harvested 165 days following the final application and processed using simulated commercial procedures into bagasse, cane juice, molasses, raw sugar, and refined sugar.

Residues of ametryn, GS 11354, GS 11355, and GS 26831 were each < 0.02 ppm in all treated fractions ( 1 sample per matrix per test), except that residues of GS 11355 were 0.02 ppm in the treated molasses sample from the 0.4x test. The sugarcane processing study is not adequate as residues were < LOQ in the RAC and the plants were only treated at 1x the maximum rate. Another processing study should be conducted using sugarcane bearing detectable residues or using sugarcane from plants treated at 5x the maximum label rate.

860.1650 Submittal of Analytical Reference Standards As of 12/ 10/ 2003, an analytical reference standard for ametryn is available at the EPA National Pesticide Standards Repository.

860.1850 Confined Accumulation in Rotational Crops The reregistration requirement for confined accumulation in rotational crops is satisfied. In an adequate confined study, [ 14C triazine] ametryn was applied three times to greenhouse grown sugarcane plants growing in a sandy loam soil. The [ 14C] ametryn was applied to the soil as a preemergence ( 8 lb ai/ A) and two post emergence soil directed applications ( 4 lb ai/ A/ application), for a total of 16 lb ai/ A, which is 1x the maximum seasonal use on sugarcane grown in Puerto Rico and is the highest rate on any rotated crop. The sugarcane plants were harvest 152 days after the final treatment ( DAT), and initial attempts at planting rotational crops Ametryn Residue Chemistry Considerations  RED Barcode: D307104 21 at 153 and 259 DAT were unsuccessful due to phytotoxicity. Rotational crops of lettuce, soybean, wheat and sugar beets were successfully planted at 422 DAT and harvested at normal crop maturity.

Total radioactive residues were 0.42 ppm in mature lettuce and 0.79 ppm in mature sugar beet tops and roots. In wheat, TRR were 1.15 1.37 ppm in forage, 6.56 ppm in straw, and 1.08 ppm in grain. In soybeans, TRR were 0.41 2.11 in forage, 9.09 ppm in straw, and 0.71 ppm in seeds.

Initial solvent extraction released 64 97% of the TRR from all samples, and a total of 86 98% of the TRR was extracted following acid hydrolysis of residual solids. For the mature matrices, 62.4 84.4% of the TRR were identified. Although there were quantitative differences in metabolite levels between matrices, the metabolite profile was qualitatively similar among the various rotational crops. The major 14C residues were comprised of the hydroxylated triazine metabolites, G 35173 ( 12.5 40.7% TRR), GS 17794 ( 0.8 30.8% TRR), and G 28521 ( 4.5 12.7% TRR). Other triazine containing metabolites identified in rotational crops included GS 11354 ( ND 2.4% TRR), GS 26831/ CGA 236433 ( ND 10.7% TRR), G 34048 ( ND 3.3% TRR), and GS 17791 ( ND 1.5% TRR). Ametryn was detected in all rotation crop matrices from the 422 day PBI at levels of 0.011 0.229 ppm, accounting for 1.1 23.0% of the TRR. Analysis of solvent extractable soil 14C residues also detected ametryn, G 34048, GS 11354, GS 11355, and GS 17794 in the soil.

The results of the confined rotational crop study were similar to the metabolism of ametryn in primary crops. Ametryn is metabolized in soil and plants by N dealkylation and desulfation ( oxidation/ hydroxylation) to a variety of metabolites containing a hydroxylated triazine ring.

860.1900 Field Accumulation in Rotational Crops The reregistration requirements for field accumulation in rotational crops are satisfied provided the requested label amendments are made. Current use directions for corn allow for rotation to small grains ( e. g. wheat) the fall following application and restrict rotation to all other crops until the following year. However, draft use directions submitted by Syngenta ( 3/ 19/ 99) would specify minimum plant back intervals ( PBI) of 3 months for wheat, 10 months for soybeans, spinach, and potatoes, and 11 months for all other rotational crops.

Adequate residue data are available from extensive rotational crop field trials and processing studies depicting residues of ametryn and its three thiomethyl metabolites in the RACs and processed commodities of soybeans, sorghum, cotton, and peanuts planted  11 months following a single application of ametryn ( WP) to field corn at either 2, 4, 6 or 10 lb ai/ A ( 1x, 2x, 3x, and 5x). The data, which are discussed in detail below, indicate that residues of ametryn and its three metabolites are each < 0.02 ppm (< LOQ) in regulated RACs and processed fractions from rotational cotton, peanuts, sorghum, and soybeans planted  11 months following a 1x application of ametryn to corn. These data support a general 11 month PBI for all crops following ametryn treated corn, and indicate that rotational crop tolerances are not required. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 22 To support reduced PBIs of 3 months for small grains and 10 months for potatoes, spinach, and soybeans, Syngenta has also submitted two limited rotational crop field trials ( discussed below) depicting residues of ametryn per se in RACs from these crops planted following an application to the soil at 1x the maximum use rate for corn. The residue data for wheat, spinach and potatoes are adequate and indicate that residues of ametryn were < 0.02 ppm in all regulated RACs from wheat, spinach and potatoes planted  3 or  10 months following a 1x application to corn. However, the soybean residue data are not adequate and do not support reducing the PBI to 10 months for soybeans as only two samples of soybean seeds were collected from one site and samples of soybean forage and hay were not collected from either site.

Considering all of the rotational field crop data, the registrants should amend EP labels to specify PBIs of 3 months for small grains, 10 months for spinach and potatoes, and 11 months for all other crops planted in rotation with corn.

HED also notes that no rotational crop intervals have been proposed following application( s) of ametryn to sugarcane. Although sugarcane grown in HI, PR and FL is not typically rotated with other crops, sugarcane grown in the Mississippi Delta region ( TX and LA) is typically rotated after 3 years to soybeans or corn. Considering the maximum use rates on sugarcane in LA and TX ( 6 6.8 lb ai/ A/ crop cycle) and the available residue data from the extensive rotational crop field trials ( 3x and 5x tests) discussed below, rotational crop tolerances will not be required provided that the label is amended to restrict rotation to soybean, sorghum, or cotton with a PBI of 11 months following application of ametryn to sugarcane. No rotational crop restriction is needed for corn since it is labeled as a primary crop for ametryn use.

Extensive rotational field trials. In a total of 14 tests conducted in the major cotton growing regions, cotton was planted  11 months following a single application of ametryn ( 80% WP) to a primary crop of corn at a rate of 2 lb ai/ A ( 6 tests), 4 lb ai/ A ( 4 tests), 6 lb ai/ A ( 2 tests), or 10 lb ai/ A ( 2 tests). Duplicate samples of cottonseed were collected 122 189 day after planting ( DAP) from each test. Residues of ametryn and the three metabolites were each < 0.02 ppm in all 28 treated samples of cottonseed, including samples from the 5x tests. Bulk samples of undelinted cottonseeds from one of each of the 1x, 3x, and 5x tests were also processed into delinted seeds, hulls, kernels, meal, soapstock, and oil. Residues of ametryn and the three metabolites were each < 0.02 ppm in all processed fractions.

In a total of 17 tests conducted in the major peanut growing regions of the U. S., peanuts were planted  11 months following a single application of ametryn ( 80% WP) to a primary crop of corn at a rate of 2 lb ai/ A ( 7 tests), 4 lb ai/ A ( 6 tests), 6 lb ai/ A ( 2 tests), or 10 lb ai/ A ( 2 tests). At maturity ( 116 150 DAP), duplicate samples of peanut nutmeats and vines were collected from 15 tests and duplicate samples of peanut hay were collected from 17 tests. Residues of ametryn and the three metabolites were each < 0.02 ppm in all 30 samples of peanut nutmeats and vines, and all 34 samples of hay, including samples from 5x tests. Bulk samples of peanuts from one of each of the 1x, 3x, and 5x tests were also processed into hulls, kernels, expeller presscake, soapstock and oil. Residues of ametryn and the three metabolites were each < 0.02 ppm in all processed fractions. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 23 In a total of 21 tests conducted throughout the U. S., sorghum was planted  11 months following a single application of ametryn ( 80% WP) to a primary crop of corn at a rate of 2 lb ai/ A ( 10 tests), 4 lb ai/ A ( 7 tests), 6 lb ai/ A ( 2 tests), or 10 lb ai/ A ( 2 tests). For each test, duplicate forage and hay samples were collected at 56 60 DAP; duplicate silage stage forage samples were collected at 71 116 DAP; and duplicate grain and stover samples were collected at 113 182 DAP. Residues of ametryn and the three metabolites were each < 0.02 ppm in all 42 samples each of sorghum forage, silage stage forage, hay, grain and stover, including samples from the 5x tests. Bulk samples of grain from one of each of the 1x, 3x, and 5x tests were also processed by dryand wet milling into bran, grits, flour and germ. Residues of ametryn and the three metabolites were each < 0.02 ppm in all processed fractions.

In a total of 18 tests conducted throughout the U. S., soybeans were planted  11 months following a single application of ametryn ( 80% WP) to a primary crop of corn at a rate of 2 lb ai/ A ( 9 tests), 4 lb ai/ A ( 5 tests), 6 lb ai/ A ( 2 tests), or 10 lb ai/ A ( 2 tests). For each test, duplicate forage and hay samples were collected at 59 92 DAP, and duplicate samples of seeds were collected at maturity ( 126 198 DAP). Residues of ametryn and the three metabolites were each < 0.02 ppm in all 38 samples of seeds, including samples from the 5x tests. For forage, residues of all three metabolites were each < 0.02 ppm in all 38 samples of forage from all tests. Residues of ametryn were also < 0.02 ppm in 36 of the forage samples from all of the 1x, 2x, 3x tests and one of the 5x tests. In the other 5x test, residues of ametryn were 0.03 ppm in two forage samples. For soybean hay, residues of all three metabolites were each < 0.02 ppm in all hay samples ( n= 41), with the exception of one hay samples from one 5x tests with residues of GS 11354 at 0.02 ppm. Residues of ametryn in hay were < 0.02 ppm in 20 out of 21 samples from the 1x tests, with one sample bearing ametryn residues of 0.04 0.07 ppm. HED previously concluded in the Ametryn Update that the detectable residues in the single 1x treated hay sample were artifactual. For the 2x tests, residues of ametryn in hay were < 0.02 0.10 ppm, with detectable residues in 5 of the 12 samples. Residues of ametryn in hay were also < 0.02 0.07 ppm in 3 of the 4 samples from the 3x tests and were 0.03 0.11 ppm in all 4 samples from the 5x tests. Bulk samples of soybean seeds from one of each of the 1x, 3x, and 5x tests were also processed into hulls, meal, soapstock, and oil. Residues of ametryn and the three metabolites were each < 0.02 ppm in all processed fractions, except for residues of GS 11355 were detected at 0.02 0.03 ppm in hulls from the 3x and 5x tests. However, apparent residues of GS 11355 were also detected at 0.02 ppm in the control samples of hulls. Therefore, the low level detection of GS 11355 in the treated hull samples is considered an artifact.

44783702. mem. wpd Limited rotational field trials. In limited field rotational crop trials conducted at two sites ( NC and IL), ametryn ( 80% DF) was applied to the bare soil at 2.0 lb ai/ A ( 1x the maximum rate for corn). Winter wheat was planted at 3 4 months after treatment, and soybeans, spinach, and potatoes were planted 8 10 months after treatment. With the exception of soybeans, duplicate samples of each of the representative RAC commodities were harvested at intervals reflecting normal agricultural practices. Wheat forage was harvested at 60 228 DAP, wheat hay was harvested 186 265 DAP, wheat grain and straw were harvested 219 301 DAP, potato tubers Ametryn Residue Chemistry Considerations  RED Barcode: D307104 24 were harvested 94 139 DAP, and spinach leaves were harvested 58 84 DAP. Samples of soybean forage and hay were not collected from either trial and soybean seeds were harvested ( 160 DAP) from only one of the two sites. All samples were analyzed for residues of ametryn, but residues of the three thiomethyl metabolites ( GS 11354, GS 11355 and GS 26831) were not determined. At both test sites, residues of ametryn were < 0.02 ppm in all samples of rotational wheat ( forage, hay, straw, and grain) from the 3 or 4 month PBI and in spinach and potatoes from the 8 or 10 month PBIs. Residues were also < 0.02 ppm in soybean seeds from the 10 month PBI at one site. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 25 Table 5. Residue Chemistry Science Assessment for Reregistration of Ametryn ( PC Code 080801).

GLN Data Requirements Current Tolerances ( ppm) [ § 180.258] Additional Data Needed? MRID Nos. 1 860.1200: Directions for Use N/ A = Not Applicable Yes See Table 3 and Appendix 1 860.1300: Nature of the Residue  Plants N/ A No 41662301 41662302 441079012 860.1300: Nature of the Residue  Animals N/ A No 41662303 41662304 41662305 41662306 439310012 860.1340: Residue Analytical Method  Plant Commodities N/ A No 3 41557102 41557103 41872304 42391601  Livestock commodities N/ A No 444777012 444777022 860.1360: Multiresidue Method N/ A No 413972014 414234014 860.1380: Storage Stability Data  Plant Commodities N/ A No 41557101 43335902 43342401 447837012  Livestock commodities N/ A No 5 444777042 860.1400: Magnitude of the Residue  Water, Fish, and Irrigated Crops N/ A No 860.1460: Magnitude of the Residue  Food Handling N/ A No 860.1480: Magnitude of the Residue  Meat, Milk, Poultry, Eggs  Fat, Meat, and Meat Byproducts of Cattle, Goats, Hogs, Horses, and Sheep None established No 444777062  Milk  Eggs and the Fat, Meat, and Meat Byproducts of Poultry None established No6 444777052 860.1500: Crop Field Trials Root and Tuber Vegetables  Cassava, root 0.1 No7  Tanier 0.25 No7  Yam, true, tuber 0.25 No7 Cereal Grains  Corn, grain 0.25 No 41909501  Corn, sweet, kernel plus cob with husks removed 0.25 Yes 8 Forage, Fodder and Straw of Cereal Grains  Corn, forage and stover 0.5 No 41909501 Ametryn Residue Chemistry Considerations  RED Barcode: D307104 Table 5. Residue Chemistry Science Assessment for Reregistration of Ametryn ( PC Code 080801).

GLN Data Requirements Current Tolerances ( ppm) [ § 180.258] Additional Data Needed? MRID Nos. 1 26 Miscellaneous Commodities  Banana 0.25 No9 41872303  Pineapple 0.25 No 41909502  Pineapple, fodder and forage 0.25 No10  Sugarcane, cane 0.25 No11 41846601  Sugarcane, fodder and forage 0.25 No10 860.1520: Processed Food/ Feed  Corn, grain None No 42391602  Pineapple None No 41909502  Sugarcane None Yes12 41846601 860.1650: Submittal of Analytical Reference Standards N/ A No 860.1850: Confined Accumulation in Rotational Crops N/ A No 41986301 41986302 860.1900: Field Accumulation in Rotational Crops N/ A No 42391602 447837022 Ametryn Residue Chemistry Considerations  RED Barcode: D307104 27 1. Bolded references were discussed in the Ametryn Phase 4 Review, dated 11/ 19/ 90 from S. Funk. Unless otherwise noted, all other references were reviewed or discussed in conjunction with the Ametryn Reregistration Update ( 12/ 9/ 94).

2. DP No. D307104, W. Donovan, 03 NOV 2004 3. Method AG 563 has undergone a successful independent laboratory method validation trial and has been validated using 14C labeled samples from the corn and sugarcane metabolism studies.

4. The Ametryn Update indicated that Multiresidue Method Testing studies had been submitted for ametryn and its thiomethyl metabolites and hydroxy triazine metabolites, but did not summarize the findings of these studies.

5. The available storage stability data for livestock commodities are from a 14 month interim report of a study designed to run for 20 months. In order to cover the maximum sample storage interval for eggs from the poultry feeding study, the registrant may submit the final report detailing the stability of ametryn and its metabolites after 20 months of frozen storage.

6. Data from the feeding study together with the adequate poultry metabolism study are sufficient to assess the need for tolerances in poultry commodities. Considering the current dietary exposure of poultry, HED concludes that there is no reasonable expectation of finite residues occurring in poultry commodities [ 40 CFR § 180.6( a)( 3)].

7. Syngenta is not supporting uses on cassava, yams, and tanier, and there is no indication that another party will be supporting these uses. Therefore, tolerances on these commodities should be revoked.

8. Data are required depicting residues of ametryn and its three thiomethyl metabolites in/ on sweet corn ears ( kernels plus cob with husks removed). Alternatively, the use on sweet corn should be deleted from all EPs.

9. Syngenta is no longer supporting the use of ametryn on bananas or plantains and has removed these uses from its label for the 80% DF.

10. Forage and fodder of pineapple and sugarcane are no longer considered significant livestock feed items and are therefore not regulated.

11. The available sugarcane residue data are adequate provided the maximum use rate per crop cycle is restricted to a maximum of 12 lb ai/ A at all locations.

12. The sugarcane processing study is not adequate. Residues were < LOQ (< 0.02 ppm) in/ on sugarcane ( RAC), bagasse, molasses, and sugar derived from plants treated at 12 lb ai/ A/ crop; however, this rate is equivalent to only 1x the maximum rate. Another processing study should be conducted using sugarcane bearing detectable residues or using sugarcane from plants treated at up to 5x the maximum label rate. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 28 TOLERANCE REASSESSMENT SUMMARY Tolerance Reassessments for Ametryn The tolerances listed in 40 CFR § 180.258( a and c) are currently expressed in terms of ametryn ( 2 ethylamino) 4( isopropylamino) 6( methylthio) s triazine per se. The ametryn risk assessment team has determined that the residues of concern for tolerance and risk assessment purposes consists of ametryn per se. A summary of ametryn tolerance reassessments is presented in Table 6.

Tolerances Listed Under 40 CFR § 180.258 ( a and c):

Adequate residue data are available to reassess the established tolerances on bananas, corn ( forage, grain, and stover), pineapples, and sugarcane. However, data are not available to support the tolerance on sweet corn, kernels plus cobs with husks removed. If no registrant intends to support the use on sweet corn, then this tolerance should be revoked once use directions for sweet corn are deleted from all EPs.

Although Syngenta, the basic producer, has deleted uses on bananas and plantains from its label, adequate residue data are available to support a banana tolerance if another registrant intends to support this use. However, use directions for bananas and plantains must be amended to reflect the use pattern supported by the available residue data. In accordance with § 180.1( h), the tolerance on banana will cover plantains.

The available residue data indicate that tolerances can be lowered for all commodities ( see Table 6). Tolerances on corn grain, forage, and stover should be split to include field and pop corn ( e. g. Corn, field, grain and Corn, pop, grain)

Based on the available livestock metabolism and feeding studies, there is no reasonable expectation of finite residues occurring in livestock commodities. Therefore, tolerances for livestock commodities are not currently required.

The tolerances on forage and fodder of pineapples and sugarcane should be revoked as these commodities are no longer regulated, and the tolerances on cassava, tanier, and yams should be revoked as uses on these crops are not being supported. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 29 Table 6. Tolerance Reassessment Summary for Ametryn.

Commodity Current Tolerance ( ppm) Range of Residues 1 ( ppm) Tolerance Reassessment 1 ( ppm) Comment/[ Correct Commodity Definition]

Tolerances Listed Under 40 CFR § 180.258( a):

Banana 0.25 < 0.02 0.04 Revoke Use is not being supported.

Corn, forage 0.5 < 0.02 0.10 0.1 Tolerances for forage, grain and stover should each be split into separate tolerances for Corn, field and Corn, pop. Corn, grain 0.25 < 0.02 0.05 2 Corn, stover 0.5 < 0.02 0.05 2 Corn, sweet, kernel plus cob with husks removed 0.25 No data TBD 3 Residue data remain outstanding. If uses on sweet corn are deleted from EPs, then this tolerance should be revoked.

Pineapple 0.25 < 0.02 0.05 0.05 2 Pineapple, fodder 0.25 not applicable Revoke These commodities are no longer regulated livestock feed items Pineapple, forage 0.25 not applicable Sugarcane, cane 0.25 < 0.02 0.05 2 Sugarcane, fodder 0.25 not applicable Revoke These commodities are no longer regulated livestock feed items Sugarcane, forage 0.25 not applicable Tanier 0.25 no data Revoke Uses are not being support on these crops. Yam, true, tuber 0.25 no data Tolerances Listed under 40 CFR 180.258( c):

Cassava, root 0.1 no data Revoke Use is not being supported 1 The range of residues for ametryn per se. 2 The LOQ for the current enforcement method is 0.05 ppm for ametryn per se. 3 TBD = to be determined. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 30 Codex/ International Harmonization There are no questions with respect to Codex/ U. S. tolerance compatibility as there are no Codex MRLs for residues of ametryn. There are also no Canadian MRLs for ametryn; however, Mexico has established MRLs for ametryn ( ametrina) on several crops. A comparison of the Mexican MRLs and the corresponding reassessed U. S. tolerances is presented in Table 7.

Table 7. Mexican MRLs and applicable U. S. tolerances for Ametryn. Recommendations are based on conclusions following reassessment of U. S. tolerances.

Mexican MRLs Reassessed U. S. Tolerance, ppm Recommendation and Comments Commodity, As Defined MRL ( mg/ kg)

Corn 0.25 grain and stover  0.05 forage  0.1 The available residue data support the lower tolerances on all commodities. Pineapple 0.25 0.05 Plantain 0.25 Revoke Sugar cane 0.25 0.05 Ametryn Residue Chemistry Considerations  RED Barcode: D307104 31 BIBLIOGRAPHY Study Citations 41397201 Yokley, R. ( 1990) Determination of Ametryn, Prometryn, and Metabolites by U. S. Food and Drug Administration Multiresidue Method Testing: Lab Project Number: ABR 89064: ABR 77060: 102065. Unpublished study prepared by Ciba Geigy Corp. 78 p.

41423401 Williams, R. ( 1990) Multiresidue Method Testing of Atrazine, Simazine, and their Chloro and Hydroxy traizine Metabolites in Crops and Animal Tissues: Lab Project ID: ABR 89010. Unpublished study prepared by Ciba Geigy Corp. 130 p.

41557101 Beidler, W. ( 1990) Ametryn: Storage Stability of Ametryn and Selected Metabolites in Crops Under Freezer Storage Conditions ( Six Month Interim Report): Lab Project Number: ABR 90058. Unpublished study prepared by Ciba Geigy Corp. 94 p.

41557102 Vargo, J. ( 1990) Analytical Method for the Determination of Ametryn and Metabolites GS 11354, GS 11355, and GS 26831 in Crops and Crop Fractions by Gas Chromatography: Lab Project No: AG 563. Unpublished study prepared by Ciba Geigy Corp. 57 p.

41557103 Morris, A.; Clayton, F. ( 1990) Method Validation Ruggedness Trial for Ciba Geigy Method AG 563, Analytical Method for the Determination of Ametryn and Metabolites GS 26831 in Crop Fractions by Gas Chromatography: Final Report: Lab Project Number: 90 0078 CGAG. Unpublished study prepared by EN CAS Analytical Laboratories. 19 p.

41662301 Detra, R.; Chib, J. ( 1990) Ametryn: Metabolism of Triazine carbon 14 Ametryn in Sugarcane: Lab Project Number: N/ 0963/ 1800. Unpublished study prepared by Battelle Columbus Div. 94 p.

41662302 Detra, R.; Chib, J. ( 1990) Ametryn: Metabolism of Triazine carbon 14 Ametryn in Corn: Lab Project Number: N/ 0963/ 1800. Unpublished study prepared by Battelle. 130 p.

41662303 Liu, D. ( 1990) Ametryn: Metabolism of carbon 14 Ametryn in Laying Hens: Analysis and Quantitation of Metabolites in Eggs, Edible Tissues, and Excreta: Lab Project Number: RPT0024. Unpublished study prepared by Xenobiotic Laboratories, Inc. 350 p.

41662304 Lin, P. ( 1990) Metabolism Study in Laying Hens Feeding carbon 14 Ametryn: Lab Project Number: P01736. Unpublished study prepared by Biological Test Center. 43 p. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 32 41662305 Liu, D. ( 1990) Ametryn: Metabolism of carbon 14 Ametryn in Lactating Goats: Analysis and Quantitation of Metabolites in Milk, Edible Tissues, and Excreta: Lab Project Number: RPT0023. Unpublished study prepared by Xenobiotic Laboratories, Inc. 142 p.

41662306 Lin, P. ( 1990) Metabolism Study in Lactating Goat Feeding carbon 14 Ametryn: Lab Project Number: P01734. Unpublished study prepared by Biological Test Center. 53 p.

41846601 Selman, F. ( 1991) Ametryn Magnitude of Residues in Sugarcane Forage , Stripped Cane, and Stripped Cane Processed Fractions Resulting from Applications of Evik 80W: Lab Project Number: ABR 91002. Unpublished study prepared by Ciba Geigy Corp. 417 p.

41872303 Selman, F. ( 1991) Ametryn Magnitude of Residues in Whole Bananas, Banana Peel, and Banana Pulp Resulting From Application of Evik 80W: Lab Project Number: ABR 91003. Unpublished study prepared by Ciba Geigy Corp. 159 p.

41872304 Vargo, J. ( 1991) Validation of Analytical Method AG 563 for the Determination of Ametryn, GS 11354, GS 11355, and GS 26831 in Corn and Sugarcane: Lab Project Number: ABR 90049. Unpublished Study prepared by Ciba Geigy Corp. 50 p.

41909501 Selman, F. ( 1991) Ametryn: Magnitude of Residues in Field Corn Forage, Fodder, Grain, and Processed Corn Grain Fractions Resulting From Applications of EVIK 80W: Lab Project Number: ABR 91001. Unpublished study prepared by Ciba Geigy Corporation. 507 p.

41909502 Wong, L. ( 1991) Ametryn: Pineapple Residue Study: Lab Project Number: 36 5294: PGA ES 91 5294: 96 20 26. Unpublished study prepared by Hawaiian Sugar Planters' Association. 208 p.

41986301 Thede, B. ( 1991) Uptake and Metabolism in Greenhouse Grown Rotational Crops Grown after Triazine Carbon 14 Ametryn Treated Sugarcane: Lab Project Number: ABR 91043. Unpublished study prepared by Ciba Geigy Corp. 114 p.

41986302 Kazee, B. ( 1991) Analytical Report: Uptake and Metabolism of in Greenhouse Grown Rotational Crops Grown after Triazine Carbon 14 Treated Sugarcane: Lab Project Number: N0963 18R. Unpublished study prepared by Battelle, Columbus Div. 63 p.

42391601 Vargo, J. ( 1991) Analytical Method for the Determination of Ametryn, Prometryn and Metabolites GS 11354, GS 11355 and GS 26831 in Corn Soapstock and Cottonseed Soapstock by Gas Chromatography including Validation Data: Lab Project Number: METHOD AG 581. Unpublished study prepared by Ciba Geigy Corp. 38 p. Ametryn Residue Chemistry Considerations  RED Barcode: D307104 33 42391602 Selman, F. ( 1992) Ametryn: Magnitude of the Residues in Field Corn Forage, Silage Stage Fodder, Fodder, Grain and Processed Corn Grain Fractions Resulting from Application of Evik 80W: Amendment 1: Lab Project Number ABR 91001. Unpublished study prepared by Ciba Geigy Corp. in coop with ABC Labs, Inc.; EN CAS Analytical Labs; Harris Labs, Inc. and others. 1335 p.

43335902 Eudy, L. ( 1994) Storage Stability of Ametryn and Selected Metabolites in Crops Under Freezer Storage Conditions: Lab Project Number: ABR 94020: 102925: 248 89. Unpublished study prepared by Ciba Geigy Corp. 159 p.

43342401 Ciba Geigy Corp. ( 1994) Sample Storage of Greenhouse Grown Rotational Crops Grown After Triazine( carbon 14) Ametryn Treated Sugarcane: Response to EPA Review: Lab Project Number: N 0963 18R: ABR 91043. Unpublished study. 6 p.

43931001 Wu, J. ( 1995) Ametryn: Storage Stability on Ametryn: Goat and Hen Metabolism: ( Supplement): Lab Project Number: RPT0023: RPT0024: 88085. Unpublished study prepared by Xenobiotic Labs, Inc. 27 p.

44107901 Thalacker, F.; Ash, S. ( 1996) ( Carbon 14) Ametryn: Nature of the Residue in Bananas: Lab Project Number: HWI 6117 270: 318 94: 94.255. Unpublished study prepared by Hazleton Wisconsin, Inc. 141 p.

44477701 Lin, K. ( 1997) Determination of Residues of Ametryn, GS 11354, GS 11355, and GS 26831 in Animal Tissue, Milk, and Egg: Lab Project Number: AG 649: 632 95: 102925. Unpublished study prepared by Novartis Crop Protection, Inc. 55 p. { OPPTS 860.1340}

44477702 Lin, K. ( 1997) Validation of Analytical Method AG 649 for Determination of Ametryn, GS 11354, GS 11355, and GS 26831 in Animal Tissues, Milk, and Poultry Eggs by Capillary Gas Chromatography: Lab Project Number: ABR 97127: 631 95: ANPHI 96003. Unpublished study prepared by Novartis Crop Protection, Inc. 133 p. { OPPTS 860.1340}

44477703 Hayworth, C. ( 1997) Stability of Ametryn and Selected Metabolites in Processed Fractions Under Freezer Storage Conditions: 6 Month Interim Report: Lab Project Number: ABR 97124: 213 96: 102925. Unpublished study prepared by Novartis Crop Protection, Inc. 107 p. { OPPTS 860.1380}

44477704 Hayworth, C. ( 1997) Stability of Ametryn and Selected Metabolites in Meat, Milk, and Eggs Under Freezer Storage Conditions: 14 Month Interim Report: Lab Project Number: ABR 97126: 222 96: 102925. Unpublished study prepared by Novartis Crop Protection, Inc. 98 p. { OPPTS 860.1380} Ametryn Residue Chemistry Considerations  RED Barcode: D307104 34 44477705 Hamilton, L. ( 1997) Ametryn Magnitude of the Residues in Meat and Eggs Resulting from the Feeding of Three Levels to Poultry: Lab Project Number: ABR 96110: 134 95: BIOL 95005. Unpublished study prepared by Novartis Crop Protection, Inc. 187 p. { OPPTS 860.1480}

44477706 Boyette, S. ( 1997) Ametryn Magnitude of the Residues in Meat and Milk Resulting from the Feeding of Three Levels to Dairy Cattle: Lab Project Number: ABR 96046: 144 95: BIOL 95006. Unpublished study prepared by Novartis Crop Protection, Inc. 186 p. { OPPTS 860.1480}

44783701 Hayworth, C. ( 1999) Stability of Ametryn and Selected Metabolites in Processed Fractions Under Freezer Storage Conditions: Final Report: Lab Project Number: 213 96. Unpublished study prepared by Novartis Crop Protection, Inc. 100 p. { OPPTS 860.1380}

44783702 Lin, K. ( 1999) Ametryn Field Rotational Crops Following Bare Ground Application of Evik 80W: Final Report: Lab Project Number: 80 95: 102925: 80 95 A. Unpublished study prepared by Novartis Crop Protection, Inc. 107 p. { OPPTS 860.1900} Ametryn Residue Chemistry Considerations  RED Barcode: D307104 35 Agency Memoranda Citations Table 8. Agency Memoranda Citations.

Date DP Barcode CB No. From To MRID Nos. Subject 12/ 9/ 94 D165469, D167228,

D167229, D180728,

D182840, D182842,

D190031, D206668,

D206842 8140, 10230,

10617, 10618,

12934, 12935,

12936, 14228,

14259 R. Perfetti K. Davis 41662301 41662306,

41846601, 41872303,

41872304, 41909501,

41909502, 42391601,

42391602, 43342401,

43335902 Response to the Ametryn DCI: Update List B Case No. 2010; Chemical No. 080801.

12/ 22/ 94 D209893 14812 R. Perfetti K. Davis None Response to the Ametryn DCI: List B Case No.

2010; Chemical No. 080801. Data Waiver Request 11/ 3/ 04 D309463 None W. Donovan M. Howard 44107901 DER: Banana Metabolism Study 43931001 DER: Supporting Storage Stability Data for Goat and Poultry Metabolism Studies 44477701, 44477702 DER: Residue Analytical Method for Livestock commodities 44477704 DER: Interim Storage Stability Data for Residues in Livestock commodities 44783701, 44477703 DER: Storage Stability Data for Residues in Pineapples and Plant Processed Commodities 44477705 DER: Poultry Feeding Study 44477706 DER: Cattle Feeding Study 44783702 DER: Field Rotational Crop Data Ametryn Residue Chemistry Considerations  RED Barcode: D307104 36 List of Attachments 1. Food Use Pattern Table for Ametryn 2. 43931001. der. wpd 3. 44107901. der. wpd 4. 44477701. der. wpd 5. 44477704. der. wpd 6. 44477705. der. wpd 7. 44477706. der. wpd 8. 44783701. der. wpd 9. 44783702. der. wpd cc ( with all Attachments): W. Donovan RDI: HED ChemSAC ( 22 SEP 2004), D. Drew ( 13 OCT 2004) W. H. Donovan: 821G: CM# 2:( 703) 305 7330: 7509C: RRB3 Ametryn Residue Chemistry Considerations  RED Barcode: D307104 37 ATTACHMENT 1 Food/ Food Use Pattern Table for Ametryn Generated by BEAD/ OPP TABLE A2. FOOD/ FEED USE PATTERNS SUMMARY FOR Ametryn ( ANSI) ( CASE 2010)

Current As Of: 04/ 02/ 2003 Printed On: 02/ 10/ 2004 Appendix 1  Page 1 SITE NAME LIMITATIONS Application Timing ( for any Reg.# at any rate)

Application Type ( for any Reg.# at any rate)

Application Equipment ( for any Reg.# at any rate) Max. Single Appl.

Rate to a Single Site Max. Seasonal Rate Max. #

Apps/

cc & yr M R I R E I PHI/ PGI/ PSI Use Limitations ( May not apply to all Reg. # s)

BANANA Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Foliar Basal spray treatment/ Broadcast/ Spray Ground/ Sprayer 8 lb A 24 lb/ yr NS NS 30 12 h Geographic allowable: Other Postplant Basal spray treatment/ Spray Ground/ Sprayer 8 lb A 24 lb/ yr NS NS 90 12 h Geographic allowable: HI PR CORN, FIELD 30 day( s) prefeeding, pregrazing and preharvest intervals.

Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Geographic allowable: AL AR AZ CA CO CT DE FL GA IA ID IL IN KS KY LA MA MD ME MI MN MO MS MT NC ND NE NH NJ NM NV NY OH OK OR PA RI SC SD TN TX UT VA VT WA WI WV Foliar Basal spray treatment/ Broadcast Sprayer 2 lb A 2 lb/ yr NS NS NS 12 h Postemergence Directed spray Sprayer 2 lb A NS NS NS NS 12 h Geographic allowable: AK HI TABLE A2. FOOD/ FEED USE PATTERNS SUMMARY FOR Ametryn ( ANSI) ( CASE 2010)

Current As Of: 04/ 02/ 2003 Printed On: 02/ 10/ 2004 Appendix 1  Page 2 SITE NAME LIMITATIONS Application Timing ( for any Reg.# at any rate)

Application Type ( for any Reg.# at any rate)

Application Equipment ( for any Reg.# at any rate) Max. Single Appl.

Rate to a Single Site Max. Seasonal Rate Max. #

Apps/

cc & yr M R I R E I PHI/ PGI/ PSI Use Limitations ( May not apply to all Reg. # s)

CORN, POP 30 day( s) prefeeding, pregrazing and preharvest intervals.

Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Geographic allowable: AL AR AZ CA CO CT DE FL GA IA ID IL IN KS KY LA MA MD ME MI MN MO MS MT NC ND NE NH NJ NM NV NY OH OK OR PA RI SC SD TN TX UT VA VT WA WI WV Foliar Basal spray treatment/ Broadcast Sprayer 2 lb A 2 lb/ yr NS NS NS 12 h Postemergence Directed spray Sprayer 2 lb A NS NS NS NS 12 h Geographic allowable: AK HI CORN, SWEET 30 day( s) prefeeding, pregrazing and preharvest intervals.

Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Geographic allowable: AL AR AZ CA CO CT DE FL GA IA ID IL IN KS KY LA MA MD ME MI MN MO MS MT NC ND NE NH NJ NM NV NY OH OK OR PA RI SC SD TN TX UT VA VT WA WI WV Foliar Basal spray treatment/ Broadcast Sprayer 2 lb A 2 lb/ yr NS NS NS 12 h Postemergence Directed spray 2 lb A NS NS NS NS 12 h Geographic allowable: AK HI TABLE A2. FOOD/ FEED USE PATTERNS SUMMARY FOR Ametryn ( ANSI) ( CASE 2010)

Current As Of: 04/ 02/ 2003 Printed On: 02/ 10/ 2004 Appendix 1  Page 3 SITE NAME LIMITATIONS Application Timing ( for any Reg.# at any rate)

Application Type ( for any Reg.# at any rate)

Application Equipment ( for any Reg.# at any rate) Max. Single Appl.

Rate to a Single Site Max. Seasonal Rate Max. #

Apps/

cc & yr M R I R E I PHI/ PGI/ PSI Use Limitations ( May not apply to all Reg. # s)

Sprayer PINEAPPLE 160 day( s) preharvest interval.

Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Postharvest Broadcast/ Spray Sprayer 8 lb A 30 lb/ cc NS NS 30 12 h 160 day( s) preharvest interval.

Postplant Broadcast/ Spray Sprayer 8 lb A 30 lb/ cc NS NS 30 12 h PLANTAIN Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Foliar Basal spray treatment/ Broadcast/ Spray Ground/ Sprayer 8 lb A 24 lb/ yr NS NS 30 12 h Geographic allowable: Other Postplant Basal spray treatment/ Spray Ground/ Sprayer 8 lb A 24 lb/ yr NS NS 90 12 h Geographic allowable: HI PR TABLE A2. FOOD/ FEED USE PATTERNS SUMMARY FOR Ametryn ( ANSI) ( CASE 2010)

Current As Of: 04/ 02/ 2003 Printed On: 02/ 10/ 2004 Appendix 1  Page 4 SITE NAME LIMITATIONS Application Timing ( for any Reg.# at any rate)

Application Type ( for any Reg.# at any rate)

Application Equipment ( for any Reg.# at any rate) Max. Single Appl.

Rate to a Single Site Max. Seasonal Rate Max. #

Apps/

cc & yr M R I R E I PHI/ PGI/ PSI Use Limitations ( May not apply to all Reg. # s)

SUGARCANE Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark.

Do not apply through any type of irrigation system.

Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.

Do not contaminate water, food, or feed by storage or disposal.

Do not enter treated areas without protective clothing until sprays have dried.

Groundwater restriction.

Rotational/ plant back crop restriction.

Foliar Band treatment/ Basal spray treatment/ Broadcast/ Soil band treatment Aircraft/ Band sprayer/ Ground/ Sprayer ( L)

4 lb A NS 3/ cc NS 30 12 h Geographic allowable: FL LA PR Postemergence Broadcast Ground/ Sprayer 2 lb A NS 3/ cc NS NS 12 h Geographic allowable: TX Preemergence Basal spray treatment/ Broadcast/ Soil broadcast treatment Ground/ High pressure sprayer/ Sprayer 8 lb A 16 lb/ cc 3/ cc NS 30 12 h Geographic allowable: HI PR TX Ratoon Band treatment/ Basal spray treatment/ Broadcast/ Soil band treatment Band sprayer/ Ground/ Sprayer ( L)

8 lb A NS 3/ cc NS 30 12 h Geographic allowable: FL HI LA PR Tops Broadcast Sprayer 2 lb A NS NS NS NS 12 h Geographic allowable: LA When needed Broadcast Aircraft 4 lb A NS NS NS NS 12 h PRODUCT NUMBERS CONTAINED IN THIS REPORT 000100 00786, 048273 00003, 051036 00105 HOMEOWNER PRODUCTS CONTAINED IN THIS REPORT None TABLE A2. FOOD/ FEED USE PATTERNS SUMMARY FOR Ametryn ( ANSI) ( CASE 2010)

Current As Of: 04/ 02/ 2003 Printed On: 02/ 10/ 2004 Appendix 1  Page 5 SITE NAME LIMITATIONS Application Timing ( for any Reg.# at any rate)

Application Type ( for any Reg.# at any rate)

Application Equipment ( for any Reg.# at any rate) Max. Single Appl.

Rate to a Single Site Max. Seasonal Rate Max. #

Apps/

cc & yr M R I R E I PHI/ PGI/ PSI Use Limitations ( May not apply to all Reg. # s)

HEADER ABBREVIATIONS Site Name  The site name refers to the entity ( crop, building, surface or article) where a pesticide is applied and/ or which is being protected.

Limitations  Precautionary statements related to the use of the product( s).

Application Timing  The timing of pesticide application and is the primary application sort ( not aggregated).

Application Type  The type of pesticide application ( aggregated).

Application Equipment  The equipment used to apply pesticide ( aggregated).

Max. Single Appl. Rate to a Single Site  Maximum Dose for a single application to a single site. System calculated.

Max Seasonal Rate  The maximum amount of pesticide that can be applied to a site in one growing season (/ cc) and during the span of one year (/ yr).

Max. # Apps/ cc & yr  Maximum Number of Applications per crop cycle and per year.

M R I  Minimum Retreatment Interval ( days) ( at any rate). The minimum interval between pesticide application ( days).

R E I  ReEntry Interval  The minimum amount of time that must elapse before workers can reenter a treated area.

PHI/ PGI/ PSI Use Limitations ( May not apply to all Reg.# s)  Preharvest/ Pregrazing/ Preslaughter Interval use limitations pertinent to the application.

Current As Of:  The label data for the listed products in this report is current of this date.

ABBREVIATIONS AN  As needed NA  Not Applicable NS  Not Specified ( on label)

( L)  The dosage information provided is from the label in terms of product ( e. g., ounces, gallons, or pounds of the product) because there was insufficient information ( e. g., missing density, area, or active ingredient percentages) to provide converted dosage information. This report provides active ingredient percentage in the product for the reported chemical for all unconverted label dosage information if this information is available. This active ingredient percentage information is displayed next to the form code abbreviations ( e. g., 80% WP).

APPLICATION RATE cwt : Hundred Weight nnE xx : nn times ( 10 power  xx), for instance, " 1.234E 04" is equivalent to ". 0001234"