UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES TXR No. 0052264 MEMORANDUM Date: 12/ 3/ 03 Subject: 2,4 D: Health Effects Division ( HED) Metabolism Assessment Review Committee ( MARC) Decision Document. DP Barcodes D293119 and D293128. Chemical I. D. No. 030001. Case No. 0073. Meeting date: 9/ 3/ 03.

From: William J Hazel, Ph. D., Chemist, Reregistration Branch 3/ HED ( 7509C) and Linda Taylor, Ph. D., Toxicologist, Reregistration Branch 3/ HED ( 7509C)

Through: Richard Loranger, Ph. D., HED MARC Chair ( 7509C) and Whang Phang, Ph. D., Branch Senior Scientist, Reregistration Branch 3/ HED ( 7509C)

To: Yan Donovan, HED MARC Executive Secretary ( 7509C)

Introduction The MARC met on 9/ 3/ 03 to discuss the 2,4 dichlorophenoxyacetic acid ( 2,4 D) residues of concern in plants, livestock, rotational crops, and drinking water.

Material Reviewed A briefing document ( D293119) prepared by William Hazel ( RRB1), Linda Taylor ( RRB1), Mark Corbin ( EFED), and James Hetrick ( EFED). The briefing document is attached to this decision document as Appendix 1; the briefing document was not filed separately.

MARC Members in Attendance: Abdallah Khasawinah, Alberto Protzel, Christine Olinger, Yan Donovan, Richard Loranger, Leung Cheng, William Wassell, P. V. Shah, Sheila Piper, Leonard Keifer.

MARC Members in Absentia: John Doherty Alternate Members in Attendance: George Kramer, David Soderberg, and Thuy Nguyen.

Nonmembers in Attendance: Mark Corbin, William Hazel. MARC Decision Table The MARC recommendations for degradates and metabolites to be included in the dietary risk assessment as well as those to be included in the tolerance expression are summarized in Table 1. Table 2 presents the chemical structures identified from the 2,4 D plant and livestock metabolism studies presently available. Table 3 provides chemical structures of environmental degradates.

Table 1. Summary of MARC Decisions for 2,4 D.

Chemical: 2,4 D Date: 9/ 3/ 03 Residues of Concerna Matrix For Risk Assessment For Tolerance Expression Plants  primary crops 2,4 D, both free and conjugated, determined as the acid 2,4 D, both free and conjugated, determined as the acid Plants  rotational crops 2,4 D, both free and conjugated, determined as the acid 2,4 D, both free and conjugated, determined as the acid Livestock  ruminant 2,4 D, both free and conjugated, determined as the acid 2,4 D, both free and conjugated, determined as the acid Livestock  poultry 2,4 D, both free and conjugated, determined as the acid 2,4 D, both free and conjugated, determined as the acid Fish and shellfish 2,4 D, both free and conjugated, determined as the acid 2,4 D, both free and conjugated, determined as the acid Water Parent N/ A aThe HED Metabolism Committee, in 1993, determined that 2,4 D per se is the residue of concern and that tolerances listed at 40 CFR § 180.142 are to be defined as " residues of 2,4 D, both free and conjugated, determined as the acid" ( R. Perfetti, 6/ 16/ 93, TXR No. 0052001 and clarification by W. Smith, 12/ 10/ 93, D197063).

Rationale:

Plants  treated and rotated:

$ In treated wheat forage and straw, 2,4 D comprised 70 80% of the TRR, three hydroxylated metabolites comprised 11 13%, and 2,4 dichlorophenol ( 2,4 DCP) contributed 0.5 0.9% TRR. In grain, 2,4 D was the only compound identified at 6% of the TRR. The majority of the TRR was characterized as being incorporated into endogenous plant compounds such as cellulose, protein, and starch at up to 45% TRR. Refer to Table 2 for chemical structures.

$ In lemon treated postharvest with 2,4 D Isopropyl ester ( IPE), the IPE was rapidly deesterified resulting in up to 69% 2,4 D after 20 weeks. Hydroxylated metabolites and 2,4 DCP were all present at < 1% TRR.

$ In treated potato, 50 60% TRR was 2,4 D. The remainder of the TRR existed as hydroxylated metabolites and 4 6 unknown polar metabolites together accounting for 42 50% of the TRR.

$ In confined rotational crops planted into soil treated at 1.1x the maximum label rate, virtually all of the TRR was incorporated into natural plant constituents. Only traces of 2,4 D and 2,4 dichloroanisole were detected in radish tops each at 0.0005 ppm ( 0.5% TRR).

$ Minor metabolites such as hydroxylated metabolites and 2,4 DCP are not expected to be significantly more toxic than the parent. Therefore, MARC concluded that for plants, parent 2,4 D, both free and conjugated, determined as the acid, are the residues of concern for risk assessment and tolerance expression.

Livestock:

$ The major residue in milk and tissues was 2,4 D, accounting for 47% TRR in milk, 21% TRR in liver, 53% TRR in kidney, 45% TRR in fat, and 38% TRR in muscle.

$ Minor amounts of 2,4 DCP were tentatively identified in milk ( 5% TRR) and fat ( 2.3% of TRR), and 4 CPA was identified in milk ( 6.9% TRR). See chemical structure in Table 2.

$ Several other non polar components ( designated NP1, NP2, and NP3) were detected in tissues; however, these metabolites may be the result of uptake of non polar impurities known to be present in the test material.

$ In poultry, the major identified component in eggs and tissues was 2,4 D, accounting for 23% TRR in eggs, 25% TRR in fat, 18% TRR in liver, and 76% TRR in kidney. Minor amounts of 2,4 DCP were also identified in eggs ( 7.3% TRR) and liver ( 4.4% TRR).

$ An earlier HED Metabolism Committee decision to delete 2,4 dichlorophenol ( 2,4 DCP) from the livestock tolerance expression for 2,4 D ( R. Perfetti, 6/ 16/ 93, TXR No. 0052001) was upheld by the MARC, i. e., 2,4 DCP is not of concern for either the tolerance expression or for risk assessment at the levels expected in livestock tissues and considering the likely lower toxicity of 2,4 DCP compared to 2,4 D.

Water:

$ The major degradates in the aerobic soil metabolism study were CO 2 (< 50% of applied radioactivity, AR) and bound residues (< 60%); small amounts of 2,4 DCP (< 3.5%) and 2,4 DCA (< 2.8%) were also detected. Refer to Table 3 for chemical structures.

$ Major residues under aerobic aquatic conditions were chlorohydroquinone (< 16% of AR), CO 2 (< 16%), and bound residues (< 39%) with lesser amounts of 2,4 DCP (< 5%).

$ Under anaerobic aquatic conditions, the major residues were 2,4 DCP (< 35%), CO 2 (< 31%), and bound residues (< 41%) as well as lesser amounds of 4 chlorophenol (< 2%).

$ In six aquatic field dissipation studies ( three each with the BEE ester and the DMA salt), 2,4 D was, by far, the predominant residue. These studies represent " real world" conditions. 2,4 D ( combined with small amounts of the parent BEE ester form in three studies) comprised 92 100% of the detected residues which included 2,4 D, 2,4 D BEE ester, 2,4 dichlorophenol, 4 chlorophenol, and 4 chlorophenoxyacetic acid. MARC does not think that 2,4 dichlorophenol, 4 chlorophenol, or 4 chlorophenoxyacetic acid will potentially be significantly more toxic than the parent; therefore, they can be excluded from risk assessment. ° 2,4 DCP is the major residue (< 35%) only under anaerobic aquatic conditions which is not the major route of degradation; 2,4 DCP has been determined not to be of concern in drinking water for risk assessment at the levels expected in water and considering the likely lower toxicity of 2,4 DCP compared to 2,4 D. ° Potential concern was raised regarding 1,2,4 benzenetriol and chlorohydroquinone. The 1,2,4 benzenetriol ( a demonstrated mutagen) was eliminated from concern because it is formed only via aqueous photolysis which is expected to be a minor route of 2,4 D dissipation in the environment. The MARC determined that drinking water exposure to chlorohydroquinone ( a possible carcinogen based on similarity to hydroquinone, a carcinogen) is likely to be low since it formed in only one of three aerobic aquatic metabolism studies, it formed to a significant extent only on day 27, and, from that point, dissipation was rapid ( half life

5 days).

Database Uncertainties: None identified. 4 cc: W. Hazel ( HED), L. Taylor ( HED), M. Corbin ( EFED), J. Hetrick ( EFED) Reference: MARC briefing document  D293119, 8/ 27/ 03 ( attached) W. Hazel: wjh: 722J: CM# 2:( 703) 305 7677 5 O Cl Cl O O CH 3 CH 3 O Cl Cl OH O O Cl O H OH O Cl O Cl Cl OH O O H O Cl O H OH O Cl OH Cl Cl Table 2. 2,4 D and its metabolites/ degradates.

Chemical Name Substrate MRID Structure Common Name ° ( 2,4 dichlorophenoxy) acetic acid, 2 ethylhexyl ester wheat forage and straw 42439701 2,4 D IOE ° ( 2,4 dichlorophenoxy) acetic acid wheat forage, straw, and grain 42439701 2,4 D ° ( 4 hydroxy 2,5 dichlorophenoxy) acetic acid wheat forage and straw 42439701 42615601 4 OH 2,5 D ° ( 5 hydroxy 2,4 dichlorophenoxy) acetic acid wheat forage and straw 42439701 42615601 5 OH 2,4 D ° ( 4 hydroxy 2,3 dichlorophenoxy) acetic acid wheat forage and straw 42439701 42615601 4 OH 2,3 D ° 2,4 dichlorophenol wheat forage and straw 42439701 2,4 DCP 1 % AR =% of applied radioactivity.

6 Table 3. Environmental Degradates of 2,4 D Acid Confirmed Degradate Lab Results Max % AR1 ( Study) Chemical Structure 1,2,4 benzenetriol 37 ( aqueous photolysis at pH 7)

2,4 dichlorophenol ( 2,4 DCP) 3.5 ( aerobic soil) 33 ( anaerobic aquatic soil metabolism, water + sediment) 5 ( aerobic aquatic soil metabolism, sediment)

2,4 dichloroanisole ( 2,4 DCA) 2.8 ( aerobic soil)

chlorohydroquinone ( CHQ) 16 ( aerobic aquatic soil metabolism, water)

Bound residues 1.0 ( soil photolysis) 60 ( aerobic soil) 41 ( anaerobic aquatic metabolism) 39 ( aerobic aquatic metabolism)

Carbon Dioxide 25 ( aqueous photolysis) 5 ( soil photolysis) 50 ( aerobic soil) 31 ( anaerobic aquatic metabolism) 16 ( aerobic aquatic soil metabolism) 7 Volatile compounds 4 chlorophenol 2,4 DCA 1.9 ( anaerobic aquatic metabolism) 1.9 ( anaerobic aquatic metabolism) APPENDIX 1: MARC BRIEFING DOCUMENT 8 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM Subject: 2,4 Dichlorophenoxyacetic acid ( 2,4 D). Briefing Memorandum for Meeting of HED's Metabolism Assessment Review Committee.

DP Barcode: D293119 Case No.: 0073 PC Code: 030001 Submission: S331345 Trade Names: Statesman ® , DMA ® 6 Weed Killer, Grazon ® P+ D, Crossbow ® , Weed Killer 4D, Esteron ® 6E EPA Reg. No. : Many 40 CFR § 180.142 Class: Herbicide From: William J. Hazel, Ph. D., Chemist Linda Taylor, Ph. D., Toxicologist Reregistration Branch 1 ( RRB1) Health Effects Division ( HED) ( 7509C) and Mark Corbin, Environmental Scientist James Hetrick, Ph. D., Senior Physical Scientist Environmental Fate & Effects Division ( EFED) ( 7507C)

Through: Whang Phang, Ph. D., Branch Senior Scientist RRB1/ HED ( 7509C)

To: Yan Donovan, Executive Secretary Metabolism Assessment Review Committee Health Effects Division ( 7509C)

Introduction 2,4 Dichlorophenoxyacetic acid ( 2,4 D) is an alkylchlorophenoxy herbicide used to control a variety of broadle weeds. 2,4 D may also occasionally be used as a plant growth regulator or fungicide. There are nine active ingredients ( AIs) in 2,4 D Reregistration Case 0073 that are components of a registered pesticide product labe for use on a food or feed crop; these same nine AIs are also being supported for reregistration by the Industr Task Force II on 2,4 D Research Data ( hereafter referred to as Task Force II). Chemical structures, properties, end use products of these AIs are listed in Tables 2 4 and include the acid form of 2,4 D, the sodium salt, four amine salts, and three esters. The members of Task Force II currently include Agro Gor Corp ( jointly owned b Attanor, S. A. and PBI Gordon Corp.), BASF, Dow AgroSciences, and Nufarm USA. In addition, USDA's Interregional Project No. 4 ( IR 4) is supporting the reregistration of a number of minor crop uses for 2,4 D and California Citrus Quality Council ( CCQC) is supporting selected ( postharvest) uses of 2,4 D isopropyl ester ( IP on citrus fruits.

2,4 D is currently registered by Task Force II members for food/ feed uses on a variety of field and orchard cro and aquatic sites. The 2,4 D formulation classes registered for food/ feed uses include wettable powders ( WP granules ( G), soluble concentrates in both liquid ( SC/ L) and solid ( SC/ S) forms, and emulsifiable concentrates ( EC). These formulations are typically applied as broadcast, banded, of directed ( spray or wiper) applications APPENDIX 1: MARC BRIEFING DOCUMENT 9 during dormancy or preplant, preharvest, preemergence, emergence, postemergence, or postharvest using ground or aerial equipment. Tolerances are currently established forresidues of 2,4 D per se in/ on: numerou raw agricultural commodity ( RAC) human foods derived from fruits, grasses, grains, nuts, vegetables, sugarc cotton, hops, and asparagus at 0.1 ppm to 5 ppm; processed products of sugarcane ( 5 ppm) and grains ( 2 pp fish and shellfish at 1.0 ppm and potable water at 0.1 ppm [ 40 CFR § 180.142( a) ( 1) to ( a)( 13)]. A temporary tolerance of 0.02 ppm for 2,4 D per se in/ on soybean seed expired 12/ 31/ 01 and, apparently, has been extende both years since [ 40 CFR § 180.142( a)( 11)]. A time limited tolerance of 0.1 ppm in/ on wild rice established und FIFRA Section 18 expired 12/ 31/ 02. Tolerances for residues in livestock commodities are currently establishe terms of residues of 2,4 D and/ or its metabolite 2,4 dichlorophenol [ 40 CFR § 180.142( a)( 8)]. The HED Metabol Committee, in 1993, determined that 2,4 D per se is the residue of concern and that tolerances listed at 40 CFR § 180.142 are to be defined as " residues of 2,4 D, both free and conjugated, determined as the acid" ( R. Perfett memorandum dated 6/ 16/ 93, TXR No. 0052001 and clarification in the W. Smith memorandum dated 12/ 10/ 93, D197063).

Issues to be Considered:

° Degradates of concern in plant commodities for tolerance expression and for risk assessment. ° Degradates of concern in livestock commodities for tolerance expression and for risk assessment. ° Degradates of concern in water for risk assessment.

TEAM PROPOSAL TABLE 1. Proposed Residues of Concern for 2,4 D.

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Plants 2,4 D 2,4 D Livestock 2,4 D 2,4 D Water 2,4 D Not Applicable Rationale for Selection of the Residues of Concern:

Plants:

° In wheat forage and straw, 2,4 D comprised 70 80% of the TRR, three hydroxylated metabolites comprised 13%, and 2,4 dichlorophenol ( 2,4 DCP) contributed 0.5 0.9% TRR. In grain, 2,4 D was the only compound identified at 6% of the TRR. The majority of the TRR was characterized as being incorporated into endoge plant compounds such as cellulose, protein, and starch at up to 45% TRR. ° In lemon treated postharvest with 2,4 D Isopropyl ester ( IPE), the IPE was rapidly deesterified resulting in u 69% 2,4 D after 20 weeks. Hydroxylated metabolites and 2,4 DCP were all present at < 1% TRR. ° In potato, 50 60% TRR was 2,4 D. The remainder of the TRR existed as hydroxylated metabolites and 4 6 unknown polar metabolites together accounting for 42 50% of the TRR.

Livestock:

° The major residue in milk and tissues was 2,4 D, accounting for 47% TRR in milk, 21% TRR in liver, 53% TR kidney, 45% TRR in fat, and 38% TRR in muscle. ° Minor amounts of 2,4 DCP were tentatively identified in milk ( 5% TRR) and fat ( 2.3% of TRR), and 4 CPA wa identified in milk ( 6.9% TRR). ° Several other non polar components ( designated NP1, NP2, and NP3) were detected in tissues; however, th metabolites may be the result of uptake of non polar impurities known to be present in the test material. ° In poultry, the major identified component in eggs and tissues was 2,4 D, accounting for 23% TRR in eggs APPENDIX 1: MARC BRIEFING DOCUMENT 10 TRR in fat, 18% TRR in liver, and 76% TRR in kidney. Minor amounts of 2,4 DCP were also identified in egg ( 7.3% TRR) and liver ( 4.4% TRR).

Water:

° The major degradates in the aerobic soil metabolism study are CO 2 (< 50% of applied radioactivity, AR) and bound residues (< 60%); small amounts of 2,4 DCP (< 3.5%) and 2,4 DCA (< 2.8%) were also detected. ° Major residues under aerobic aquatic conditions are chlorohydroquinone (< 16% of AR), CO 2 (< 16%), and bound residues (< 39%) with lesser amounts of 2,4 DCP (< 5%). ° Under anaerobic aquatic conditions, the major residues are 2,4 DCP (< 35%), CO 2 (< 31%), and bound residu (< 41%) as well as lesser amounds of 4 chlorophenol (< 2%). ° In six aquatic field dissipation studies ( three each with the BEE ester and the DMA salt), 2,4 D was, by far, predominant residue. These studies represent " real world" conditions. 2,4 D ( combined with small amoun of the parent BEE ester form in three studies) comprised 100% of the detected residue in two studies and, comparing maximum concentrations, was present at much greater concentrations ( 22x 960x) than those of any of the measured metabolites which included 2,4 dichlorophenol, 4 chlorophenol, and 4 chlorophenoxyacetic acid.

Rat/ dog:

° In the rat, 2,4 D is excreted mainly in the urine and basically unchanged. In the dog, excretion also occurs mainly via the urine but, in addition to intact 2,4 D, conjugates of 2,4 D and several minor metabolites are excreted.

Codex Harmonization:

° The Codex Alimentarius Commission has established several maximum residue limits ( MRLs) for residues 2,4 D in/ on various plant and animal commodities. The Codex MRLs are expressed in terms of 2,4 D per se The expression of residues for Codex MRLs and U. S. tolerances is harmonized.

Analytical Methodology:

° Both the data collection method and the enforcement method determine any salt, any ester, and conjugate 2,4 D. As a result of a step to hydrolyze the esters and conjugates, the anionic form of 2,4 D is released. A acidification step protonates the anionic form of 2,4 D which results in the more nonpolar acid form of 2,4 for quantitation. These steps increase the quantitative recovery of the residues of concern to the U. S. and Codex. APPENDIX 1: MARC BRIEFING DOCUMENT 11 O Cl Cl O O[ NH 2( CH 2 CH 2 OH) 2]+ O Cl Cl O O[ NH 2( CH 2) 2]+ CHEMICAL IDENTIFICATION AND PROPERTIES Chemical structures and other information are presented in Table 2 for 2,4 D acid and those salts and esters w registered manufacturing use and/ or end use products ( MPs/ EPs).

Table 2. 2,4 D active ingredients with registered MPs/ EPs 2,4 D acid Empirical Formula: C 8 H 6 Cl 2 O 3 Molecular Weight: 221.0 CAS Registry No.: 94 75 7 PC Code: 030001 2,4 D sodium salt ( Na) Empirical Formula: C 8 H 5 Cl 2 NaO 3 Molecular Weight: 243.03 CAS Registry No.: 2702 72 9 PC Code: 030004 2,4 D diethanolamine salt ( DEA) Empirical Formula: C 12 H 17 Cl 2 NO 5 Molecular Weight: 326.18 CAS Registry No.: 5742 19 8 PC Code: 030016 2,4 D dimethylamine salt ( DMA) Empirical Formula: C 10 H 13 Cl 2 NO 3 Molecular Weight: 266.13 CAS Registry No.: 2008 39 1 PC Code: 030019 2,4 D isopropylamine salt ( IPA) Empirical Formula: C 11 H 15 Cl 2 NO 3 Molecular Weight: 280.04 CAS Registry No.: 5742 17 6 PC Code: 030025 2,4 D triisopropanolamine salt ( TIPA) Empirical Formula: C 17 H 27 Cl 2 NO 6 Molecular Weight: 412.31 CAS Registry No.: 32341 80 3 PC Code: 030035 APPENDIX 1: MARC BRIEFING DOCUMENT Table 2. 2,4 D active ingredients with registered MPs/ EPs 12 O Cl Cl O O CH 3 CH 3 O Cl Cl O O NH+( CH 2 CHOHCH 3) 3 O Cl Cl O O O CH 3 Cl Cl O O O  [ NH 3 CH( CH 3) 2]+

2,4 D 2 butoxyethyl ester ( BEE) Empirical Formula: C 14 H 18 Cl 2 O 4 Molecular Weight: 321.20 CAS Registry No.: 1929 73 3 PC Code: 030053 2,4 D 2 ethylhexyl ester ( 2 EHE) 1 Empirical Formula: C 16 H 22 Cl 2 O 3 Molecular Weight: 333.27 CAS Registry No.: 1928 43 4 PC Code: 030063 2,4 D isopropyl ester ( IPE) Empirical Formula: C 11 H 12 Cl 2 O 3 Molecular Weight: 263.12 CAS Registry No.: 94 11 1 PC Code: 030066 1 Formerly identified as the isooctyl ester.

The available data concerning identification and some basic physicochemical properties of the active ingred are summarized in Table 3 for 2,4 D acid, salts, and esters with registered Mps/ EPs. 13 Table 3. Available data concerning identification of the active ingredient. 1 Active ingredient ( PC Code) Color Physical State Melting Point/ Boiling Point Density/ Specific Gravity Octanol/ Water Partition Coeff. Vapor Pressu 2,4 D acid ( 030001) white crystalline solid m. p. 138 141 C s. g.= 1.416 at 25 C 674 1.4 x 10 7 mm H at 25 C 2,4 D Na salt ( 030004) white powder m. p. 200 C bulk = 42.2 lb/ ft3 at 25 C N/ A 2; salt dissociates to acid water 2,4 D DEA salt ( 030016) cream powder m. p. 83 C bulk = 0.762 g/ cm3 at 25 C 2.24 x 10 2 at 25 C < 1.33 x 10 5 Pa 25 C 2,4 D DMA salt ( 030019) amber aqueous liquid m. p. 118 120 C ( PAI) s. g. = 1.23 at 20 C N/ A; salt dissociates to acid in water < 1 x 10 7 mm H at 26 C 2,4 D IPA salt ( 030025) amber aqueous liquid m. p. 121 C ( PAI) s. g. = 1.15 at 20 C N/ A; salt dissociates to acid i water 2,4 D TIPA salt ( 030035) amber aqueous liquid m. p. 87 110 C ( PAI) s. g. = 1.21 at 20 C N/ A; salt dissociates to acid i water 2,4 D BEE ( 030053) dark amber liquid b. p. 98 C s. g. = 1.225 at 20 C log = 4.13 4.17 at 25 C 2.4 x 10 6 mm H at 25 C 2,4 D 2 EHE ( 030063) dark amber liquid b. p. 300 C s. g. = 1.152 at 20 C log = 5.78 ( temp N/ A) 3.6 x 10 6 mm H ( temp N/ A)

2,4 D IPE ( 030066) pale amber liquid b. p. 240 C s. g. = 1.252 at 25 C 253.8 ± 44.4 ( temp N/ A) 5.3 x 10 6 mba APPENDIX 1: MARC BRIEFING DOCUMENT 14 1 Data assembled from Agency memoranda and comprehensive review documents referenced herein, includin the 2,4 D Reregistration Standard. 2 N/ A = Not available. APPENDIX 1: MARC BRIEFING DOCUMENT 15 Table 4. Representative 2,4 D End Use Products being Supported by the 2,4 D Task Force II 1.

EPA Reg. No. Label Acceptance Date 2 Formulation 3 Product name 2,4 Dichlorophenoxyacetic acid ( 030001)

228 315 7/ 16/ 1996 0.76% G Sweet Sixteen Weed & Feed with Triplet MC DRI 538 186 1/ 28/ 2002 0.75% G Fertilizer Plus Dicot Weed Control III 2217 579 1/ 08/ 2003 0.69% G Gordon's Trimec ® Weed & Feed 30 2217 660 8/ 23/ 2002 0.76% G Gordon's Trimec ® Weed & Feed 33 ½ 62719 218 4 3/ 08/ 2002 85% WP Statesman ® 62719 330 5 3/ 06/ 2002 2.8 lb/ gal EC Esteron 638 71368 3 5 3/ 07/ 2002 2.8 lb/ gal EC Weedone ® 638 Sodium salt 2,4 dichlorophenoxyacetate ( 030004)

5080 2 11/ 30/ 1982 17.5% P/ T Aquacide 71368 22 10/ 27/ 2000 76.8 SC/ S 2,4 D Sodium Salt Diethanolamine 2,4 dichlorophenoxyacetate ( 030016)

2217 703 7 11/ 14/ 2002 3.8 lb/ gal EC Hi Dep ® Herbicide 2217 813 3/ 15/ 2002 5.03 lb/ gal EC EH1330 Herbicide Dimethylamine 2,4 dichlorophenoxyacetate ( 030019)

228 145 7/ 31/ 2001 3.8 lb/ gal EC Weedestory ® AM 40 Amine Salt 228 331 10/ 20/ 1997 0.83% G 2,4 D Amine Weed & Feed 228 354 1/ 21/ 1999 19.2% G Depth Charge   Aquatic Herbicide 228 260 7/ 06/ 1999 80.5% SC/ S Solution Water Soluble ® 2217 2 3/ 08/ 2002 3.8 lb/ gal EC Amine 400 2,4 D Weed Killer 2217 543 7/ 11/ 2002 1.98 lb/ gal SC/ L Trimec ® Herbicide 34707 606 3/ 04/ 2002 78.9% CR Savage Dry Soluble Herbicide 34707 803 5/ 29/ 1999 3.8 lb/ gal EC Saber Herbicide 42750 21 6/ 26/ 1995 5.6 lb/ gal EC 2,4 D Amine 6 Herbicide 62719 1 6 11/ 07/ 2001 3.8 lb/ gal EC Formula 40 ® Herbicide 62719 3 10/ 13/ 2000 3.8 lb/ gal EC DMA 4 71368 1 10/ 03/ 2002 3.8 lb/ gal EC Weedar ® 64 Broadleaf Herbicide Isopropylamine 2,4 dichlorophenoxyacetate ( 030025)

62719 303 3/ 06/ 2002 3.8 lb/ gal EC IPA 4 Triisopropaolamine 2,4 dichlorophenoxyacetate ( 030035)

62719 1 6 11/ 07/ 2001 3.8 lb/ gal EC Formula 40 ® herbicide Butoxyethyl 2,4 dichlorophenoxyacetate ( 030053)

228 378 9/ 21/ 2000 19% G 2,4 D Aquatic Granules 62719 50 9/ 28/ 2001 3.8 lb/ gal EC 2,4 D BEE 4 62719 330 5 3/ 06/ 2002 2.8 lb/ gal EC Esteron 638 71368 3 3/ 07/ 2002 2.8 lb/ gal EC Weedone ® 638 71368 4 3/ 12/ 1980 19% G Aqua Kleen 2 ethylhexyl 2,4 Dichlorophenoxyacetate ( 030063)

228 139 10/ 11/ 2002 3.84 lb/ gal EC 2,4 D LV4 Ester APPENDIX 1: MARC BRIEFING DOCUMENT EPA Reg. No. Label Acceptance Date 2 Formulation 3 Product name 16 228 153 5/ 27/ 1993 0.66% G Fertilizer Plus 2,4 D 2217 77 3/ 26/ 2002 3.8 lb/ gal EC LV 400 2,4 D Weed Killer 5905 529 7/ 13/ 2001 4.7 lb/ gal EC Barrage ® HF Low Volatile Herbicide 34704 609 3/ 18/ 1997 5 lb/ gal EC Salvo ® Postemergence Broadleaf Herbicide 42750 20 11/ 16/ 2000 5.5 lb/ gal EC 2,4 D LV6 Low Volatile Herbicide 62719 9 6/ 08/ 2001 3.8 lb/ gal EC Weed Killer 4D 71368 11 2/ 17/ 2000 5.4 lb/ gal EC Weedone ® LoVol 6 Broadleaf Herbicide Isopropyl ester 2,4 dichlorophenoxyacetate ( 030066)

5481 145 12/ 28/ 2001 3.36 lb/ gal EC Citrus Fix   35935 21 4/ 13/ 1998 3.4 lb/ gal EC Alphaset IPE 64864 31 8/ 18/ 1998 3.3 lb/ gal EC Leffingwell Hivol 44 1To assist in developing tables of uses being support by the Industry Task Force II ( Agro Gor Corp, BASF, Do AgroSciences, and Nufarm USA), the Task Force II has cited labels for the Agency that include representative D active ingredients and formulations. 2Date of the most recently EPA approved label found by reviewer on the Pesticide Product Label System. 3The active ingredient for the formulated products is expressed as the acid equivalent. For formulations containing more than one 2,4 D a. i., the total 2,4 D acid equivalents is presented. 5EPA Reg. Nos. 62719 330 and 71368 3 are MAI formulations containing both the acid ( 030001) and the butoxyethyl ester of 2,4 D ( 030053) for a total acid equivalent of 2.8 lb/ gal. 6EPA Reg. No. 62719 1 is a MAI formulation containing both DMA ( 030019) and TIPA ( 030035) salts of 2,4 D for total acid equivalent of 3.8 lb/ gal. 7EPA Reg. No. 2217 703 is an MAI formulation containing both DMA ( 030019) and DEA ( 030016) salts of 2,4 D f total acid equivalent of 3.8 lb/ gal.

DIRECTIONS FOR USE There are numerous 2,4 D EPs registered under FIFRA Section 3 to the members of Task Force II. To indicate what uses are being supported by Task Force II members, Task Force II has provided the Agency with a Mast Label which SRRD agreed to have the science divisions use as the universe of supported uses for reregistrat purposes. For each use site, the Master Label generally summarizes the following information: forms of 2,4 being supported ( i. e. acid, amine salts, and/ or esters); types of formulations being supported ( i. e. EC, WP, etc limitations on the type and timing of application( s); allowed application equipment; reentry interval ( REI); maximum single and seasonal application rates; minimum retreatment interval ( RTI); regional restrictions; an restrictions on the preharvest and grazing intervals ( PHI and PGI). The Master Label does not provide details uses on labels of specific EPs. The information regarding the food/ feed and aquatic use sites on the Master L is summarized in Appendix 1 ( a separate electronic attachment to accompany this MARC briefing memo). A v brief summary of several representative label directions for use on major crops include: ( i) small grains, 1.25 lb ae/ A postemergence + preharvest, 14 d PHI, < 1.75 lb ae/ A/ season; ( ii) field corn, 1 + 0.5 + 1.5 lb ae/ A pre + postemergence + preharvest, 7 d PHI, < 3 lb ae/ A/ season; ( iii) pasture and range, 2 lb ae/ A postemergence, 7 d precutting interval; ( iv) grapes, 1.36 lb ae/ A, postbloom, 100 d PHI; orchard fruits and nuts, 2 x 2 lb ae/ A postemergence/ yr, 14 d PHI for pome fruits, 40 d for stone fruits, and 60 d PHI for nuts; and ( v) citrus plant gr regulator use, 12 200 ppm foliar application with 7 day PHI, 500 ppm postharvest application with no PHI. APPENDIX 1: MARC BRIEFING DOCUMENT 17 TOLERANCE ENFORCEMENT METHODOLOGY For the purpose of reregistration, adequate methods are available for data collection and the enforcement of p commodity tolerances. The Pesticide Analytical Manual ( PAM) Vol. II lists three GC methods ( designated as Methods A, B, and C) with microcoulometric detection and one GC method ( designated as Method D) with ele capture detection ( ECD). In a letter dated 9/ 3/ 93 ( CBRS No. 12270, DP Barcode D193335, 9/ 3/ 93, W. Smith), the Task Force II indicated that the enforcement methods currently listed in PAM Vol. II are unsuitable for determi residues of 2,4 D in wheat and poultry commodities.

Plant Commodities: The Task Force II submitted an adequate proposed enforcement method for plants ( designated as EN CAS Method No. ENC 2/ 93, described below) which has been independently validated. Adequate radiovalidation data have been submitted and evaluated for the proposed enforcement method usin samples from the wheat metabolism study. The proposed enforcement method or modifications of the enforcement method were used for data collection purposes.

Animal Commodities: The Task Force II submitted two separate ( but essentially comparable) proposed enforcement methods for determination of 2,4 D in livestock commodities. Adequate radiovalidation data hav been submitted for the method using samples of fat, kidney, and milk from the goat metabolism study and samples of eggs from the poultry metabolism study. The Agency concluded that the methods are adequate provided the registrants satisfy the following requests: ( i) submit a revised method which combines the two methods into a single method and once an adequate revised method is received the Agency will forward the method to EPA/ Beltsville for a tolerance method validation; ( ii) delete from the method all references to the us diazomethane as a derivatizing agent; and ( iii) provide complete raw data and sample calculations ( including chromatograms showing peak areas, external standard linearity curves and associated data, standard calculations, etc.).

For the GC/ ECD method ENC 2/ 93, residues are extracted from plant matrices into 0.5 M KOH in ethanol: H 2 O ( EtOH, 1: 1, v/ v) and filtered. The resulting extract is refluxed for 1 hour in 0.2 M HCl. Hydrolyzed residues are cleaned up using a C 18 solid phase extraction column by rinsing with water and hexane, and then eluting with hexane: ethyl acetate ( EtOAc, 1: 1, v/ v). Residues are then partitioned into 0.1 M Na 2 HPO 4, acidified, and partiti into diethyl ether ( Et 2 O). Residues are concentrated to dryness and then derivatized to the methyl ester with 1 boron trifluoride in methanol ( MeOH). For samples of soybean ( seed and forage), sugarcane, and rice straw, derivatized sample is then oxidized with potassium permanganate. The derivatized residues from each matrix ( except wheat forage and grain) are then partitioned into 25% toluene in hexane and cleaned up using an Alum column eluted with 25% toluene in hexane. For wheat forage and grain samples, the derivatized residues are extracted into toluene, diluted with hexane ( toluene: hexane, 1: 2, v/ v), and cleaned up using an Alumina colum eluted with 35% toluene in hexane. Methylated residues in all matrices are determined by GC/ ECD. The alkali hydrolysis step is expected to hydrolyze any 2,4 D ester that may be present as well as conjugates of 2,4 D.

MULTIRESIDUE METHODS The 10/ 97 edition of FDA PAM Volume I, Appendix I indicates that 2,4 D is partially recovered ( 50 80%) using Multiresidue Methods Section 402 E1 and 402 E2.

HAZARD CHARACTERIZATION ( From 2,4 D Toxicology Chapter of the RED dated 8/ 19/ 03)

2,4 Dichlorophenoxyacetic acid [ 2,4 D] and its amine salts [ diethanolamine ( DEA), dimethylamine ( DMA), isopropylamine ( IPA), and triisopropanolamine ( TIPA)] and esters [ butoxyethyl ester ( BEE), ethylhexyl ester ( E and isopropyl ester ( IPE)] are not acutely toxic via the oral, dermal, and inhalation routes of exposure [ Toxicit Category III], with the exception of DMA, which shows moderate [ Toxicity Category II] toxicity via the oral and dermal routes. 2,4 D and its amine salts and esters are not skin irritants [ Toxicity Categories III and IV] and no a skin sensitizer. All forms of 2,4 D show severe eye irritation [ Toxicity Category I], with the exception of BEE APPENDIX 1: MARC BRIEFING DOCUMENT 18 [ Toxicity Category III].

In general, 2,4 D undergoes limited metabolism primarily involving minor conjugation of the parent acid that i then excreted in the urine. No detectable metabolites of 2,4 D have been reported in the rat; i. e., only the pare acid is found in rat urine. In addition to 2,4 D itself, 2,4 D conjugates have been found in the urine of dogs, humans, mice, and hamsters following oral exposure. The mechanisms responsible for the renal clearance of D have been investigated in several species also. This phenoxy herbicide is actively secreted by the proximal tubules in a manner similar to paraaminohippuric acid [ PAH], and this mechanism of renal clearance for 2,4 D consistent with results seen with other phenoxy acids. It has been suggested that the observed dose depend non linear pharmacokinetics of 2,4 D are primarily due to the saturation of this renal secretory transport syste Due to a limited capacity to excrete organic acids, the dog is more sensitive to the effects of 2,4 D than the ra with respect to repeated dosing.

Following subchronic oral exposure at dose levels of 2,4 D at or above the threshold of saturation for renal clearance, the primary target organs are the eye [ retinal degeneration, cataract formation], thyroid [ increased thyroid weight, increased T3/ decreased T4, and follicular cell hypertrophy], kidney [ brush border loss in prox tubule], adrenals [ hypertrophy], and ovaries/ testes [ atrophy]. These changes are also observed following exposure to the amine salts and esters of 2,4 D. Systemic toxicity was not observed following repeated derma exposure to 2,4 D, EHE, and TIPA at or above the limit dose or following repeated dermal exposure to BEE an at the highest dose tested. Liver toxicity was observed following repeated dermal exposure to DEA, and one d [ female] occurred following dermal exposure to DMA at a high dose level.

There are no repeated inhalation exposure data available on 2,4 D. The only reliable way to characterize inhal toxicity and to quantify inhalation risk is through the use of inhalation toxicity studies. Chemicals tend to be toxic by the inhalation route than by the oral route due to rapid absorption and distribution, bypassing of the liver's metabolic protection ( portal circulation), and potentially serious portal of entry effects, such as irritatio edema, cellular transformation, degeneration, and necrosis. An inhalation risk assessment that is based on o data generally underestimates the inhalation risk because it cannot account for these factors. Therefore, a subchronic inhalation study is required for 2,4 D.

Developmental toxicity, characterized mainly as an increased incidence of skeletal variations in the rat, was observed following exposure to 2,4 D and its amine salts and esters. Malformations in the rat were observed o at dose levels that were at or above the threshold of saturation of renal clearance. Developmental toxicity was observed in the rabbit only following exposure to 2,4 D [ abortions] and DEA [ increased number of litters with fetuses with 7th cervical ribs].

Reproductive toxicity, characterized as an increase in gestation length, was observed following exposure to 2 at a dose level above the threshold of saturation of renal clearance. A repeat 2 generation reproduction study [ using the new protocol] is required to address concerns for endocrine disruption [ thyroid and immunotoxici measures].

Neurotoxicity was demonstrated following exposure to 2,4 D at relatively high dose levels. Clinical signs of neurotoxicity [ ataxia, decreased motor activity, myotonia, prostration, lateral recumbency, and impaired/ loss the righting reflex, cold to the touch] were observed in pregnant rabbits following exposure to 2,4 D and its a salts and esters. Neuropathology [ retinal degeneration] was observed following 2,4 D exposure in several stu in female rats. Incoordination and slight gait abnormalities ( forepaw flexing or knuckling) were observed follo acute dosing and increased forelimb grip strength was observed following chronic exposure to 2,4 D at dose levels that exceeded the threshold of saturation of renal clearance. A developmental neurotoxicity study in th is required on 2,4 D.

2,4 D is classified as a Group D chemical [ not classifiable as to human carcinogenicity]. Based on the overall pattern of responses observed in both in vitro and in vivo genotoxicity tests, 2,4 D was not mutagenic, althou some cytogenic effects were observed.

2,4 D affects thyroid hormone homeostasis following oral exposure, and there is a concern for endocrine disruption. Effects on the gonads in rats [ decreased testes and ovarian weights, atrophy of the ovary, uterus testis, degeneration of the seminiferous epithelium, decreased spermatozoa in epididymis, testicular degeneration, increase in gestation length] and dogs [ increased testes weight, juvenile testes and prostate, a APPENDIX 1: MARC BRIEFING DOCUMENT 19 hypospermatogenesis] are seen following exposure to 2,4 D and/ or its amine salts and esters. Although there data on thyroid hormone levels in the adult animal, there are no data with respect to thyroid hormones in the young; therefore, there is no information on whether the young are more sensitive with respect to this endpo There is no developmental neurotoxicity [ DNT] study available on 2,4 D, and the HIARC determined previousl a DNT study is required [ HED Document No. 014234]. There have been no studies on 2,4 D that specifically as its endocrine disruption potential, and there are no data on other hormonal effects. Thyroid effects [ increased thyroid weight, increased T3/ decreased T4, and follicular cell hypertrophy] have been observed in the rat follo subchronic exposure to 2,4 D and its amine salts and esters and following chronic exposure to 2,4 D [ decreas T4, increased thyroid weight, thyroid masses, and follicular cell hyperplasia ( males; interim sacrifice only)/ hypertrophy ( females; interim sacrifice only)]. Additionally, there is some concern for immunotoxicity following exposure to 2,4 D. There are clear NOAELs for each of the above mentioned effects, which occur on high dose levels; above the doses selected for overall risk assessment. Therefore, there are no residual uncertainties with regard to these effects. However, the HIARC concluded that a 2 generation reproduction st using the current protocol is required to address both the concern for thyroid effects [ comparative assessme between the young and adult animals] and immunotoxicity, as well as a more thorough assessment of the go and reproductive/ developmental endpoints. The Task Force should consult the Agency on the protocol for th study.

SUMMARY OF TOXICOLOGY ENDPOINT SELECTION ( From 5/ 1/ 03 HIARC report of 4/ 8/ 03 HIARC meeting ( TXR No. 0051866))

Table 5. Summary of Toxicological Dose and Endpoints for 2,4 D.

Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( Females 13 50 years of age) NOAEL = 25 mg/ kg/ day UF = 1000 Acute RfD = 0.025 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD( 0.025) FQPA SF ( 1)

= 0.025 mg/ kg/ day rat developmental toxicity study LOAEL = 75 mg/ kg/ day based on skeletal malformations and skeletal variations Acute Dietary ( General population including infants and children) NOAEL = 67 mg/ kg/ day UF = 1000 Acute RfD = 0.067 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD ( 0.067) FQPA SF ( 1)

= 0.067mg/ kg/ day acute neurotoxicity study in rats LOAEL = 227 mg/ kg/ day based on gait abnormalities APPENDIX 1: MARC BRIEFING DOCUMENT Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects 20 Chronic Dietary ( All populations) NOAEL= 5 mg/ kg/ day UF = 1000 Chronic RfD = 0.005 mg/ kg/ day FQPA SF = 1X cPAD = chronic RfD ( 0.005) FQPA SF ( 1)

= 0.005 mg/ kg/ day rat chronic toxicity study LOAEL = 75 mg/ kg/ day based on decreased body weight gain ( females) and food consumption ( females), alterations in hematology [ decreased RBC, HCT, and HGB ( females), platelets ( both sexes)] and clinical chemistry parameters [ increased creatinine ( both sexes), alanine and aspartate aminotransferases ( males), alkaline phosphatase ( both sexes), decreased T4 ( both sexes), glucose ( females), cholesterol ( both sexes), and triglycerides ( females)], increased thyroid weights ( both sexes at study termination), and decreased testes and ovarian weights .

Short Term Incidental Oral ( 1 30 days) NOAEL= 25 mg/ kg/ day Residential LOC for MOE = 1000 Occupational = NA rat developmental toxicity study LOAEL = 75 mg/ kg/ day based on decreased maternal body weight gain and skeletal malformations and skeletal variations Intermediate Term Incidental Oral ( 1 6 months) NOAEL = 15 mg/ kg/ day Residential LOC for MOE = 1000 Occupational = NA subchronic oral toxicity  rat LOAEL = 100 mg/ kg/ day based on decreased body weight/ bodyweight gain, alterations in some hematology [ decreased platelets ( both sexes)] and clinical chemistry [ decreased T3 ( females) and T4 ( both sexes)] parameters, and cataract formation.

Short Term Dermal ( 1 to 30 days) Oral study NOAEL= 25 mg/ kg/ day ( dermal absorption rate = 5.8%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 rat developmental toxicity study LOAEL = 75 mg/ kg/ day based on decreased maternal body weight gain and skeletal malformations and skeletal variations Intermediate Term Dermal ( 1 to 6 months) Oral study NOAEL = 15 mg/ kg/ day ( dermal absorption rate = 5.8%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 subchronic oral toxicity  rat LOAEL = 100 mg/ kg/ day based on decreased body weight/ bodyweight gain, alterations in some hematology [ decreased platelets ( both sexes)] and clinical chemistry [ decreased T3 ( females) and T4 ( both sexes)] parameters, and cataract formation. APPENDIX 1: MARC BRIEFING DOCUMENT Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects 21 Long Term Dermal (> 6 months) Oral study NOAEL= 5 mg/ kg/ day ( dermal absorption rate = 5.8%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 rat chronic toxicity study LOAEL = 75 mg/ kg/ day based on decreased body weight gain ( females) and food consumption ( females), alterations in hematology [ decreased RBC, HCT, and HGB ( females), platelets ( both sexes)] and clinical chemistry parameters [ increased creatinine ( both sexes), alanine and aspartate aminotransferases ( males), alkaline phosphatase ( both sexes), decreased T4 ( both sexes), glucose ( females), cholesterol ( both sexes), and triglycerides ( females)], increased thyroid weights ( both sexes at study termination), and decreased testes and ovarian weights .

Short Term Inhalation ( 1 to 30 days) Oral study NOAEL= 25 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 rat developmental toxicity study LOAEL = 75 mg/ kg/ day based on decreased maternal body weight gain and skeletal malformations and skeletal variations Intermediate Term Inhalation ( 1 to 6 months) Oral study NOAEL = 15 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 subchronic oral toxicity  rat LOAEL = 100 mg/ kg/ day based on decreased body weight/ bodyweight gain, alterations in some hematology [ decreased platelets ( both sexes)] and clinical chemistry [ decreased T3 ( females) and T4 ( both sexes)] parameters, and cataract formation.

Long Term Inhalation (> 6 months) Oral study NOAEL= 5 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 1000 Occupational LOC for MOE = 100 rat chronic toxicity study LOAEL = 75 mg/ kg/ day based on decreased body weight gain ( females) and food consumption ( females), alterations in hematology [ decreased RBC, HCT, and HGB ( females), platelets ( both sexes)] and clinical chemistry parameters [ increased creatinine ( both sexes), alanine and aspartate aminotransferases ( males), alkaline phosphatase ( both sexes), decreased T4 ( both sexes), glucose ( females), cholesterol ( both sexes), and triglycerides ( females)], increased thyroid weights ( both sexes at study termination), and decreased testes and ovarian weights .

Cancer ( oral, dermal, inhalation) Classification: Group D [ not classifiable as to human carcinogenicity]

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LO = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic), RfD = referen APPENDIX 1: MARC BRIEFING DOCUMENT 22 dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable NOTE: The Special FQPA Safety Factor recommended by the HIARC assumes that the exposure databases ( dietary food, drinking water, and residential) are complete and that the risk assessment for each potential exposure scenario includes all metabolites and/ or degradates of concern and does not underestimate the potential risk for infants and children.

RESIDUE CHEMISTRY INFORMATION PLANT METABOLISM EXCERPTS FROM 24D. 003; WHEAT METABOLISM; D181885 ( 42439701)/ D186927 ( 42615601). In the wheat metabolism study, [ 14C] 2 EHE was applied to plants at tillering as a broadcast application at 1.5 lb ae/ A (

1x). TRR were 33.6 ppm in/ forage ( Table 6) harvested 10 days post treatment and 55.7 ppm in straw ( Table 7) and 0.299 ppm in grain ( Tab harvested at maturity ( 49 days post treatment). Following acid hydrolysis, 2,4 D was the major compound identified in forage ( 68.0% TRR) and straw ( 56.2% TRR). After subsequent base hydrolysis, another 8.8% of th TRR in forage and 16.1% of the TRR in straw was identified as 2,4 D. Minor metabolites ( each < 10% TRR) identified in forage and straw included: 4 hydroxy 2,5 D; 4 hydroxy 2,3 D; 5 hydroxy 2,4 D; and 2,4 DCP. The only compound identified in grain was 2,4 D ( 6.0% TRR). The majority of 14C residues in grain ( 45% TRR) wer characterized as being incorporated into natural plant constituents, such as, protein, starch and cellulose. R to Table 20 for structures of plant metabolites.

Table 6. Distribution of 14C residues in wheat forage following a single over the top spray application of isooctyl ( 2 ethylhexyl) ester of [ 14C] 2,4 D at 1.5 lb ae/ A ( 1x the maximum registered seasonal rate).

Extracts and Metabolites [ 14C] 2,4 D acid equivalents % TRR ppm Composite 10 Day Forage TRR 100.0 33.6 Ether Extract After Hydrolysis 20.4 6.84 Ether Extract ( ETH 1) 19.8 6.64 4 Hydroxy 2,5 dichlorophenoxyacetic acid a 2.8 0.936 Hydroxydichlorophenoxyacetic acid ( HPLC retention time 15.0 17.0 min.) b 0.4 0.133 Hydroxydichlorophenoxyacetic acid ( HPLC retention time 19.0 21.5 min.) c 1.0 0.345 2,4 D d 12.5 4.21 2,4 Dichlorophenol a 0.2 0.066 Unknown ( HPLC retention time 1.5 3.5 min.) 0.3 0.113 Unknown ( HPLC retention time 18.0 18.5 min.) < 0.1 0.007 Unknown ( HPLC retention time 22.0 24.0 min.) 0.2 0.080 Unknown ( HPLC retention time 29.5 37.0 min.) 0.6 0.206 Unknown ( HPLC retention time 38.0 43.0 min.) e 1.2 0.405 Unknown ( HPLC retention time 44.0 54.0 min.) 0.4 0.133 Aqueous Extract ( AQ 1) 0.6 0.198 Ether Extract ( ETH 2) 0.4 0.131 4 Hydroxy 2,5 dichlorophenoxyacetic acid a < 0.1 0.016 2,4 D d < 0.1 0.011 Unknown ( HPLC retention time 1.5 3.0 min.) 0.1 0.043 Unknown ( HPLC retention time 17.5 19.5 min.) < 0.1 0.016 Unaccounted < 0.1 0.045 Aqueous Extract ( AQ 2) 0.1 0.032 Unaccounted 0.1 0.035 Ethanol Extract After Hydrolysis 66.1 22.2 Ether Extract ( ETH 1) 57.1 19.2 4 Hydroxy 2,5 dichlorophenoxyacetic acid a 0.4 0.134 Hydroxydichlorophenoxyacetic acid 0.2 0.058 2,4 D d 55.1 18.5 2,4 Dichlorophenol a 0.1 0.038 APPENDIX 1: MARC BRIEFING DOCUMENT Extracts and Metabolites [ 14C] 2,4 D acid equivalents % TRR ppm 23 Unknown ( HPLC retention time 36.0 39.0 min.) 1.1 0.0365 Aqueous Extract ( AQ 1) 8.8 2.45 Ether Extract ( ETH 2) 7.3 2.45 4 Hydroxy 2,5 dichlorophenoxyacetic acid a 4.8 1.61 Hydroxydichlorophenoxyacetic acid ( HPLC ret. time 15.0 17.0 min.) b 1.5 0.519 Hydroxydichlorophenoxyacetic acid ( HPLC ret. time 19.0 20.5 min.) c 0.2 0.066 2,4 D d 0.4 0.120 2,4 Dichlorophenol a 0.2 0.059 Unknown ( HPLC retention time 2.0 3.0 min.) 0.1 0.034 Unknown ( HPLC retention time 22.0 23.0 min.) 0.1 0.037 Aqueous Extract ( AQ 2) 1.5 0.496 KOH Extract 12.2 4.09 Ether Soluble 8.9 2.98 2,4 D d 8.8 2.95 Unknown ( HPLC retention time 2.0 3.0 min.) 0.1 0.027 Aqueous Soluble 3 1.6 0.540 Enzyme Digestible Cellulase Digestible 0.3 0.098 Amylase Digestible 0.1 0.045 Non extractable 0.4 0.140 a Confirmed by GC/ MS. b Confirmed by GC/ MS as 4 hydroxy 2,3 dichlorophenoxyacetic acid in the supplemental study ( MRID 42615601). c Confirmed by GC/ MS as 5 hydroxy 2,4 dichlorophenoxyacetic acid in the supplemental study ( MRID 42615601). d Confirmed by one dimensional TLC and GC/ MS. e Identification by GC/ MS was unsuccessful. However, the presence of an amino acid conjugate of 2,4 D was indicated.

Table 7. Distribution of 14C residues in wheat straw following a single over the top spray application of isooc ( 2 ethylhexyl) ester of [ 14C] 2,4 D at 1.5 lb ae/ A ( 1x the maximum registered seasonal rate).

Extracts and Metabolites [ 14C] 2,4 D acid equivalents % TRR ppm Composite 49 Day Straw TRR 100.0 55.7 Ether Extract After Hydrolysis 14.3 7.95 Ether Soluble ( ETH 1) 13.9 7.77 4 Hydroxy 2,5 dichlorophenoxyacetic acid a 1.8 0.995 Hydroxydichlorophenoxyacetic acid ( HPLC retention time 15.0 16.0 min.) b 0.2 0.124 Hydroxydichlorophenoxyacetic acid ( HPLC retention time 18.5 21.0 min.) c 0.6 0.319 2,4 D d 8.1 4.51 2,4 Dichlorophenol a 0.4 0.241 Unknown ( HPLC retention time 52.0 54.0 min.) 0.3 0.140 Unknown ( HPLC retention time 2.0 3.5 min.) 0.2 0.093 Unknown ( HPLC retention time 21.5 23.0 min.) 0.2 0.101 Unknown ( HPLC retention time 30.0 36.0 min.) 0.3 0.163 Unknown ( HPLC retention time 37.0 42.0 min.) 0.5 0.256 Unknown ( HPLC retention time 43.0 51.0 min.) 0.4 0.218 Unknown ( HPLC retention time 6.5 12.0 min.) 0.9 0.482 Unknown ( HPLC retention time 16.5 18.0 min.) 0.1 0.039 Unknown ( HPLC retention time 28.5 29.5 min.) 0.1 0.031 Unknown ( HPLC retention time 55.0 60.0 min.) 0.1 0.054 Aqueous Extract ( AQ 1) 0.3 1.75 Ether Extract ( ETH 2) 0.3 0.158 4 Hydroxy 2,5 dichlorophenoxyacetic acid a < 0.1 0.022 2,4 D < 0.1 0.007 Unknown ( HPLC retention time 2.0 3.0 min.) < 0.1 0.013 Unknown ( HPLC retention time 17.5 19.5 min.) < 0.1 0.026 Unaccounted 0.2 0.091 Aqueous Extract ( AQ 2) < 0.1 0.017 Ethanol Extract After Hydrolysis 62.5 34.8 Ether Soluble ( ETH 1) 49.2 27.4 4 Hydroxy 2,5 dichlorophenoxyacetic acid a 0.5 0.274 APPENDIX 1: MARC BRIEFING DOCUMENT Extracts and Metabolites [ 14C] 2,4 D acid equivalents % TRR ppm 24 Hydroxydichlorophenoxyacetic acid ( HPLC retention time 15.0 16.0 min.) b 0.1 0.055 Hydroxydichlorophenoxyacetic acid ( HPLC retention time 19.5 20.5 min.) c 0.2 0.110 2,4 D d 47.9 26.7 Unknown ( HPLC retention time 2.0 3.5 min.) 0.5 0.301 Aqueous Extract ( AQ 1) 13.4 7.45 Ether Extract ( ETH 2) 12.0 6.69 4 Hydroxy 2,5 dichlorophenoxyacetic acid a 6.2 3.45 Hydroxydichlorophenoxyacetic acid ( HPLC ret. time 15.0 16.0 min.) b 2.2 1.2 Hydroxydichlorophenoxyacetic acid ( HPLC ret. time 19.0 20.5 min.) c 0.8 0.468 2,4 D d 0.2 0.127 2,4 Dichlorophenol a 0.5 0.301 Unknown ( HPLC retention time 22.0 23.0 min.) 0.2 0.114 Unaccounted 1.8 1.02 Aqueous Extract ( AQ 2) 1.4 0.760 KOH Extract 18.7 10.4 Ether Extractable After Acidification 17.7 9.88 2,4 D a 16.1 8.95 Unknown ( HPLC retention time 2.5 6.5 min.) 1.5 0.85 Unknown ( HPLC retention time 23.0 26.0 min.) 0.2 0.089 Aqueous Soluble 0.9 0.509 Enzyme Digestible Cellulase Digestible 1.3 0.697 Amylase Digestible 0.4 0.211 Non extractable 0.4 0.215 a Confirmed by GC/ MS. b Confirmed by GC/ MS as 4 hydroxy 2,3 dichlorophenoxyacetic acid in the supplemental study ( MRID 42615601). c Confirmed by GC/ MS as 5 hydroxy 2,4 dichlorophenoxyacetic acid in the supplemental study ( MRID 42615601). d Confirmed by one dimensional TLC and GC/ MS.

Grain Table 8 indicates that only 6.0% of TRR ( 0.018 ppm) was identified as 2,4 D in all fractions/ extracts of treated g A significant amount of bound 14C residues remained unidentified even after organic and aqueous extractions enzyme hydrolysis of the solid residues; the fractionation procedures resulted in extracts with TRR values an concentrations which are below the Agency metabolism trigger values. The remaining unidentified radioactiv includes: ( i) two unknown metabolites ( combined 17.1%, 0.051 ppm), ( ii) aqueous soluble metabolites ( comb 21.4%, 0.064 ppm), ( iii) the enzyme hydrolyzable fractions ( combined 10.1%, 0.03 ppm), and ( iv) the unaccoun radioactivity ( 36.5%, 0.109 ppm). Supplemental characterization indicates that ca. 45% of the radioactivity in g is putatively incorporated into plant cell constituents such as protein, starch and cellulose.

Table 8. Distribution of 14C residues in wheat grain following a single over the top spray application of isooc ethylhexyl) ester of [ 14C] 2,4 D at 1.5 lb ae/ A.

Extracts and Metabolites [ 14C] 2,4 D acid equivalents Treated Sample Control Sample % TRR ppm % TRR ppm Composite Grain TRR 100.0 0.299 100.0 0.169 Acetonitrile: Water Extract 3.7 0.011 2.4 0.004 2,4 D 1.3 0.004   Unknown ( HPLC retention time 2.0 3.0 min.) 0.3 0.001   Unknown ( HPLC retention time 47.0 49.0 min.) 0.3 0.001   Unaccounted 1.7 0.005

Aqueous Extract 7.7 0.023 8.3 0.014 Ether Extractable After Acid Hydrolysis 1.3 0.004   Aqueous Soluble 3.7 0.011   Unaccounted 2.7 0.008   APPENDIX 1: MARC BRIEFING DOCUMENT Extracts and Metabolites [ 14C] 2,4 D acid equivalents Treated Sample Control Sample 25 KOH Extract 28.4 0.085 18.9 0.032 Ether Extract ( ETH 1) 5.4 0.016 3.0 0.005 2,4 D 4.7 0.014   Unaccounted 0.7 0.002   Aqueous Soluble ( AQ 2) 5.7 0.017 5.9 0.010 Precipitate ( Acid Hydrolyzed) 17.4 0.052 9.5 0.017 Ether Soluble ( ETH 2) 0.7 0.002   Aqueous Soluble ( AQ 1) 12.0 0.036

Enzyme Digestible Amylase Digested 2.3 0.007 2.4 0.004 Cellulase Digested 4.7 0.014 4.7 0.008 Protease Digested 3.0 0.009 2.4 0.004 Non Extractable Solid 34.8 0.104 40.2 0.068 Acid Hydrolysis/ Ether 1.3 0.004 1.2 0.002 Acid Hydrolysis/ Aqueous 21.1 0.063 26.0 0.044 Unknown ( HPLC retention time 2.0 5.0 min.) 16.4 0.049   Unaccounted for HPLC 4.7 0.014   Unaccounted After Acid Hydrolysis 3.7 0.011   Non extractable 8.9 0.027 11.2 0.019 Total Extractable and Non Extractable 84.3 0.252 79.3 0.134 Lemons:

Proposed metabolic pathway in lemons The registrant proposed that 2,4 D IPE is rapidly metabolized in lemons treated postharvest by ester hydrolys form 2,4 D and small amounts of 2,4 dichlorophenol, which are subsequently conjugated and/ or hydroxylated the phenyl ring.

Lemon metabolism study summary The qualitative nature of 2,4 D IPE residues in stored lemons is adequately understood based on the submitte study reflecting registered use as a plant growth regulator. The metabolism in lemons is similar to that obser in wheat. The residue to be regulated in citrus is proposed to be 2,4 D. Refer to Table 9 for the metabolic pro The total radioactive residues ( TRR, expressed as [ 14C] 2,4 D IPE equivalents) found in/ on stored lemons sam at various posttreatment intervals ( 2 hours, 2 days, and 1 24 weeks) following postharvest treatment on lemon ranged from 2.091 ppm to 2.834 ppm. The extraction procedures indicate that the majority of the 14C residue w found in the peel and acetone rinsate (  95% of TRR collectively) at all sampling intervals. The radioactivity associated with pulp and juice were minimal (  5% of TRR collectively).

A substantial proportion of the 14C residues in the peel and rinse (  95% of TRR) was sufficiently characterized and identified. The major residue identified was 2,4 D ( 24.16% 67.46% TRR, 0.623 1.534 ppm) which noticeabl increased in level at each subsequent sampling interval. The test substance, 2,4 D IPE ( 0.22% 47.24% TRR, 0. 1.339 ppm) declined at subsequent intervals indicating rapid ester hydrolysis to 2,4 D. Other minor metabolit ( each < 1% TRR) identified were 2,4 dichlorophenol, 2,5 dichloro 4 hydroxyphenoxyacetic acid, and 2,3 dichlo hydroxyphenoxyacetic acid/ 2,4 dichloro 5 hydroxyphenoxyacetic acid. 2,4 D Heptanone ester and the 2,4 D dimer were identified and confirmed but not quantitated.

The qualitative nature of 2,4 D IPE residues in stored lemons is adequately understood based on the submitte study reflecting registered use as a plant growth regulator. The metabolism in lemons is similar to that obser in wheat. The residue recommended to be regulated in citrus is 2,4 D. APPENDIX 1: MARC BRIEFING DOCUMENT 26 Excerpt from D205343; MRID 43290501; lemon metabolism following postharvest dip; R. Perfetti; 24D. 026 Table 9. Summary of characterized/ identified residues in/ on lemons that had been dipped in a formulation of [ 14C] 2,4 D IPE and wax and rinsed with acetone. a 2 hours posttreatment 2 weeks posttreatment 10 weeks posttreatment 20 weeks posttreatment Metabolites/ Fractions % TRR ppm % TRR ppm % TRR ppm % TRR ppm Identified 2,4 D IPE 47.24 1.339 0.33 0.008 0.22 0.005 0.22 0.005 2,4 D 24.16 0.684 26.57 0.623 44.48 1.074 67.46 b 1.534 2,4 Dichlorophenol       0.76 b 0.017 2,5 D 4 OH       0.46 b < 0.011 2,3 D 4 OH/ 2,4 D 5 OH       0.59 b < 0.014 2,4 D heptanone ester   N/ Q c

2,4 D dimer   N/ Q c

Total Identified 71.40 2.023 26.90 0.631 44.70 1.079 69.49 < 1.581 Characterized Fraction I 0.18 0.005 3.04 0.071 6.70 < 0.162 0.11 0.003 Fraction II 0.76 0.021 3.11 0.073 4.67 < 0.114 3.19 < 0.072 Fraction III 10.78 0.306 41.87 0.981 34.70 0.839 0.010 < 0.003 Fraction V 4.89 0.139 5.63 0.133 0.51 0.012 0.99 0.023 Fraction VII 11.06 0.314 15.66 0.367 3.22 < 0.078 1.57 0.036 Metabolite A       3.97 0.090 Metabolite B       5.22 0.119 Metabolite C       2.73 0.062 Metabolite D       1.11 0.025 Metabolite E       0.41 0.009 Metabolite F       1.48 0.034 Metabolite G       3.09 0.070 Metabolite H       0.46 0.010 Metabolite K       0.83 0.019 EtOAc soluble       1.71 0.039 Aqueous soluble       0.73 0.017 Total Identified/ Characterized 99.07 2.808 96.21 2.256 94.50 < 2.284 97.10 2.212 Non extractable d 0.91 0.026 3.79 0.088 5.45 0.132 2.69 0.061 a Totals include metabolites/ fractions identified/ characterized in the acetone rinse.

b Includes conjugated or bound analogs identified following hydrolysis.

c N/ Q = Not quantified; identification of 2,4 D heptanone ester and 2,4 D dimer in Fraction II hydrolysate.

d Includes unextracted juice and spent pulp from the 2 hour and 2 week intervals. APPENDIX 1: MARC BRIEFING DOCUMENT 27 Potato:

In the potato metabolism study, TRR in mature vines and tubers were 6.26 and 0.577 ppm, respectively, 20 da following the second of two foliar broadcast applications of [ 14C] 2,4 D 2 EHE totaling 0.62 lb ae/ A ( 4.4x maxim labeled rate). In potato tubers, solvent extractable 14C residues accounted for > 95% of the TRR. The largest single component of the extractable 14C residues was identified as 2,4 D ( 42.8 46.3% TRR); minor portions we comprised of 2,4 D EHE ( 0.5 8.3% TRR) and 4 hydroxy 2,5 D ( 6.4% TRR). The remainder of the extractable radioactivity was comprised of 4 6 polar unknowns together accounting for 42.4 50.4% of the TRR. Upon acid hydrolysis, these unknowns were converted to 4 hydroxy 2,5 D ( 14.6% TRR) and 4 chlorophenoxy acetic acid CPA, 24.4% TRR). Acid hydrolysis of unextracted 14C residues released an additional 8.7% of the TRR, the ma portion of which was comprised of 2,4 D ( 2.3% TRR), 4 CPA ( 1.6% TRR), and 4 hydroxy 2,5 D ( 0.9% TRR). Ple refer to Table 10.

Excerpt from D210592; 43496101; potato metabolism; D. Miller; 2/ 22/ 96; 24D. 045 Table 10. Summary of characterization/ identification of 14C residues in potato tubers from plants treated twic with [ 14C] 2,4 D 2 EHE at 0.31 lb ae/ A, for a total of 0.61 lb ae/ A.

Metabolite % TRR ppm a 2,4 D 2 EHE 0.5  8.3 0.003  0.048 2,4 D acid 45.1  46.3 0.260  0.267 4 hydroxy 2,5 D b 15.5 0.089 4 CPA b 26.0 0.150 Total identified 87.1  96.1 0.503  0.554 Polar unknowns b 10.5 c 0.060 Solids 5.4 6.4 0.031 0.037 a Expressed as 2,4 D acid equivalents. b Metabolites and unknowns isolated following acid hydrolysis of ACN extractable residues and solvent extracted solids. c Comprised of at least nine unknowns each accounting for 0.2 2.8% of the TRR.

CONFINED ROTATIONAL CROPS Excerpt from D207980 re: Confined rotational crops/ D. Miller/ 24D. 040 Radioactive residues in lettuce, radishes, and wheat were < 0.001 0.06 ppm and 0.01 0.084 ppm from plantings made 30 and 139 days, respectively, following an application of [ 14C] 2,4 D to a sandy loam soil at 2.17 lb ae/ A the maximum label rate). Radioactive residues were adequately characterized in all crop matrices. The major the 14C residues were characterized as either aqueous soluble or unextractable and reflected the incorporatio radioactivity into natural components. In wheat grain, radioactivity incorporated into starch accounted for 69 of the TRR, and 6 34.6% of the TRR was associated with isolated cellulose and lignin fractions from lettuce, ra tops, and wheat straw from the 30 day PBI and wheat forage and straw from the 139 day PBI. Acidic organic fractions, which would have contained 2,4 D residues, were

0.004 ppm in all matrices from both PBIs followi either direct solvent extraction or acid hydrolysis and solvent extraction. Aqueous EtOH soluble residues we 0.003 0.017 ppm, and were only > 0.01 ppm in radish tops ( 30 day PBI) and wheat straw ( 30 and 139 day PBIs) Organosoluble residues released by hydrolysis of solvent extracted solids also accounted for minor amounts radioactivity (< 10% TRR and < 0.01 ppm). The only metabolites detected in any matrix were 2,4 D and 2,4 dichloroanisole, which were each detected at 0.0005 ppm following acid hydrolysis of EtOH/ H 2 O soluble residues from radish tops.

LIVESTOCK METABOLISM APPENDIX 1: MARC BRIEFING DOCUMENT 28 Ruminant metabolism:

EXCERPT FROM D191013; 42749701; RUMINANT METABOLISM; 24D. 006 In the ruminant metabolism study, a lactating goat was dose orally with [ 14C] 2,4 D for three consecutive days level equivalent to 483 ppm in the diet (~ 0.6x the maximum theoretical dietary burden). At sacrifice, the TRR w 0.224 ppm in liver, 1.44 ppm in kidney, 0.037 ppm in muscle, 0.088 ppm in fat, and 0.020 ppm in milk ( Day 3). major residue in milk and tissues was 2,4 D, accounting for 47% TRR in milk, 20.5% TRR in liver, 52.7% TRR in kidney, 45.4% TRR in fat, and 37.8% TRR in muscle ( Table 11). Minor amounts of 2,4 DCP were also tentativel identified in milk ( 5% TRR) and fat ( 2.3% of TRR), and 4 CPA was identified in milk ( 6.9% TRR). Several other polar components ( designated NP1, NP2, and NP3) were detected in tissues; however, these metabolites may the result of uptake of non polar impurities known to be present in the test material.

Table 11. Summary of 14C residue identification/ characterization in goat milk and tissues.

Milk ( day 3) Liver Kidney Fat Muscle Component % TRR ppm % TRR ppm % TRR ppm % TRR ppm % TRR ppm 2,4 D 47.0 0.095 20.5 0.046 53.6 0.773 45.4 0.040 37.8 0.014 2,4 dichloro phenol 5.0 0.010     2.3 0.002

p CPA 6.9 0.014   a

Total identified 58.9 0.119 20.5 0.046 53.6 0.773 47.7 0.042 37.8 0.014 Nonpolar 1 1.0 0.002 14.7 0.033 10.3 0.148 3.4 0.003 2.7 0.001 Nonpolar 2   17.9 0.040 22.0 0.317 13.6 0.012 24.3 0.009 Nonpolar 3   5.4 0.012 4.1 0.059

Unknowns 5.5 0.011 6.7 0.015   3.3 0.003

Total 67.9 0.137 65.2 0.146 90.0 1.297 68.0 0.060 64.8 0.024 a Detected at 6.3% ( 0.014 ppm) in the preliminary liver extraction.

Poultry metabolism:

EXCERPT FROM D186732; 42605201; POULTRY METABOLISM; 24D. 004 In the poultry metabolism study, laying hens were dosed orally with [ 14C] 2,4 D for seven consecutive days at levels equivalent to 18.3 ppm in the diet ( 11.4x the maximum theoretical dietary burden). At sacrifice, the TRR were 0.0297 ppm in liver, 0.714 ppm in kidney, < 0.002 ppm in breast muscle, 0.008 ppm in thigh muscle, 0.027 ppm in fat, and 0.0178 ppm in eggs. The major identified component in eggs and tissues was 2,4 D, accounti 23.0% TRR in eggs, 25.1% TRR in fat, 18.2% TRR in liver, and 75.6% TRR in kidney ( Tables 12 15). Minor amou of 2,4 DCP were also identified in eggs ( 7.3% TRR) and liver ( 4.4% TRR).

Table 12. Distribution of 14C residues in the eggs of laying hens administered [ 14C] 2,4 D.

Fractions and Metabolites TRR, [ 14C] 2,4 D equivalents % ppm Composited Day 7 Egg TRR 100.0 0.0178 Initial Ether Extract ( EO1) 84.8 0.0151 Acetonitrile Extract ( ACN HPLC) 51.7 0.0092 2,4 D 23.0 0.0041 2,4 dichlorophenol 7.3 0.0013 Unidentified 2.8 0.0005 Unaccounted by HPLC 19.1 0.0034 Ether soluble ( POSTEO1) 24.2 0.0043 Unaccounted following Cleanup 9.0 0.0016 Post extract Aqueous Filtrate ( EA2) 1.7 0.0003 APPENDIX 1: MARC BRIEFING DOCUMENT 29 Tissue Unextractable ( PE) 16.3 0.0029 Total Extractable and Unextractable ( sum of EO1, EA2, and PE) 102.8 0.0183 Total Identified a 30.3 0.0054 Total Unidentified a, b 41.6 0.0079 Total Unaccounted a 28.1 0.0050 a Calculated by the study reviewer. b Calculations based on 100% recovery.

Table 13. Distribution of 14C residues in the fat of laying hens administered [ 14C] 2,4 D.

Fractions and Metabolites TRR, [ 14C] 2,4 D equivalents % ppm Composited Fat TRR 100.0 0.0271 Initial Acetonitrile Extract ( EO1) 21.8 0.0059 Ether ( EO2, after base hydrolysis of EO1 aqueous phase) 81.9 0.0222 Hexane ( EO2 Hex) 17.3 0.0047 Chloroform ( EO2 CH) 13.3 0.0036 Aqueous ( EO2 H 2 O) 8.9 0.0024 Acetonitrile ( EO2 ACN) 31.4 0.0085 2,4 D 25.1 0.0068 Unaccounted by HPLC 6.3 0.0017 Non extractable < 0.1 < MQL a Total Extractable and Non extractable ( sum of EO1 and EO2) 103.7 0.0281 Total Identified b 25.1 0.0068 Total Unidentified b, c 68.6 0.0196 Total Unaccounted ( reported by registrant) 6.3 0.0017 a MQL = Minimum Quantifiable Limit by LSS, 25.7 dpm. b Calculated by study reviewer. c Calculations based on 100% recovery.

Table 14. Distribution of 14C residues in the liver of laying hens administered [ 14C] 2,4 D.

Fractions and Metabolites TRR, [ 14C] 2,4 D equivalents % ppm Composited Liver TRR 100 0.0297 Initial Ether Extract ( EO1) 53.9 0.0160 HPLC Analyzable ( chloroform extract after repeated fractionation of EO1) 34.7 0.0103 2,4 D a, b 18.2 0.0054 2,4 dichlorophenol a 4.4 0.0013 Unaccounted by HPLC 11.8 0.0035 Aqueous soluble ( EO1 EA1, sum of two fractions obtained after repeated fractionation of EO1) 7.1 0.0021 Insoluble Residue c 2.0 0.0006 Unaccounted after Clean up 9.8 0.0029 Ether ( EO2, following acid hydrolysis of unextractable residues) 29.0 0.0086 Aqueous ( EA1, remaining after aqueous partitioning and filtering of EO2) d  < MQLe Tissue Non extractable ( PE) 8.4 0.0086 Total Extractable and Non extractable ( sum of EO1, EO2, and PE) 91.3 0.0271 Total Identified 22.6 0.0067 Total Unidentified 47.1 0.0140 Total Unaccounted ( reported by registrant) 21.6 0.0064 a Identified by HPLC. b Identified by TLC. c Data not accounted for in the registrant's flow chart but were included in the registrant's summary table. d Data not listed on registrant's summary table but were included on registrant's flow chart. e MQL = Minimum Quantifiable Limit by LSS, 25.7 dpm. APPENDIX 1: MARC BRIEFING DOCUMENT 30 Table 15. Distribution of 14C residues in the kidney of laying hens administered [ 14C] 2,4 D.

Fractions and Metabolites TRR, [ 14C] 2,4 D equivalents % ppm Composited Kidney TRR 100.0 0.7140 Initial Ether Extract ( EO1) 11.6 0.0826 HPLC Analyzable ( after TLC purification) a 2.6 0.0188 2,4 D b 0.1 0.0008 Three Unknowns c 0.4 0.0026 Unaccounted by HPLC 0.9 0.0063 Unaccounted after cleanup 8.9 0.0638 Ether ( EO2, following acid hydrolysis of aqueous extract of EO1) 58.0 0.414 2,4 D b, d, e 57.3 0.4090 One Unknown 0.7 0.0050 Ether ( EO3, following base hydrolysis of aqueous extract of EO2) 16.7 0.119 2,4 D b 16.7 0.119 Ether and Acetonitrile ( EO4 and EO5) 4.5 0.0319 HPLC Analyzable ( after acidification and chloroform extraction) 1.5 0.0107 2,4 D b 1.5 0.0107 Aqueous soluble ( EA45TL) 0.9 0.0062 Insoluble Residue ( 45 PE) 0.5 0.0034 Unaccounted after Cleanup 1.6 0.0116 Aqueous soluble ( EA1 and EA3, combined aqueous filtrates after repeated fractionation) 1.4 0.0102 Tissue Unextractable ( PE) 0.1 0.0009 Total Extractable and Unextractable ( sum of EO1, EO2, EO3, EO4, EO5, and PE) 92.3 0.659 Total Identified f 76.9 0.5487 Total Unidentified f 11.7 0.0836 Total Unaccounted ( reported by registrant) 11.4 0.0817 a Data not accounted for in the registrant's flow chart but were included in the registrant's summary table. b Identified by HPLC. c Sum of three unknowns respectively accounting for 0.1% of TRR ( 0.0008 ppm), 0.1% of TRR, ( 0.0007 ppm), and 0.2% of TRR ( 0.0011 ppm). d Identified by TLC. e Confirmed by GC MS. f Calculated by the study reviewer.

WATER, FISH, AND IRRIGATED CROPS Nature of the Residues in Fish and Shellfish. In summary, the metabolism of 2,4 D in fish is adequately understood ( Table 16). The TRR was 0.406 ppm in bluegill sunfish fillets exposed to 10.6 ppm of [ 14C] 2,4 D un static conditions for 4 consecutive days. Approximately 95% of the TRR was extractable and 90% of the TRR identified/ characterized by HPLC. The principal residue was 2,4 D, accounting for 80% of the TRR ( 0.325 ppm 2,4 DCP accounted for 8% of the TRR ( 0.032 ppm). The identities of the metabolites were confirmed by GC/ MS The registrant also tentatively identified radioactive residues in fish viscera. In viscera, 100% of the TRR was extractable. 2,4 D and 2,4 DCP each accounted for approximately 30% of the TRR and a mixture of CPAA and accounted for 40% of the TRR. The registrant suggested that the additional metabolites detected in the visce were due to microbial degradation. Literature was cited to support this hypothesis. The 2,4 D metabolic path in fish is proposed by the registrant to proceed via formation of 2,4 DCP and conjugates of 2,4 D and 2,4 DCP Based on these data, the residues to be regulated in fish and shellfish are the same as in livestock and are recommended to include both free and conjugated 2,4 D.

Excerpt from D208093; MRID 43378801; fish metabolism; 24D. 027; R. Perfetti APPENDIX 1: MARC BRIEFING DOCUMENT 31 Table 16. Summary of characterization/ identification of 14C residues in fillet samples from bluegill sunfish do with [ 14C] 2,4 D at 10.6 ppm for four consecutive days.

Metabolite/ Component % TRR ppm 2,4 D 80.0 0.325 2,4 DCP 7.9 0.032 Total identified 87.9 0.357 Polar Unknowns 2.2 0.009 Solids 0.0 < LOQ Magnitude of Residues in Fish and Shellfish. Adequate studies are available depicting the magnitude of 2,4 D residues in catfish, bluegill sunfish, crayfish, and clams exposed to water containing 6.0 ppm of 2,4 D in a s system. The maximum supported rate for aquatic uses of 2,4 D is 10.8 lb ae/ acre ft, which is equivalent to a concentration of 4 ppm. Therefore, the studies were conducted at 1.5x the maximum concentration. In the tw studies, 2,4 D residues in edible tissues plateaued within 6 hours for both species of fish, 12 hours for clams, 8 days for crayfish. During the 15 day exposure in one test, maximum 2,4 D residues in edible tissues were 0 ppm in catfish, 0.067 ppm in bluegill sunfish, and 1.1 ppm in crayfish. During the 28 day exposure in another maximum 2,4 D residues in edible tissues were 0.59 ppm in clams and 1.18 ppm in crayfish. Based on exposu 6 ppm ( 1.5x), these studies support tolerances for 2,4 D residues in fish at 0.1 ppm and in shellfish at 1.0 ppm Residues in Water. The Office of Ground Water and Drinking Water has established a Maximum Contaminant Level of 0.07 ppm for 2,4 D in drinking water. The aquatic use patterns currently being supported by the Task Force II also prohibit the use of 2,4 D treated water for use as potable water unless an approved assay indicat that 2,4 D concentrations are

0.07 ppm.

Data pertinent to residues in water were reviewed in the Residue Chemistry Chapter of the 1988 2,4 D Reregistration Standard. This information along with other previous reviews was summarized in an HED amended use petition review ( CBTS No. 9026, 3/ 3/ 92, G. Otakie). In studies by the Department of the Army, application of the DMA salt to ponds at 4 lb ae/ A resulted in 2,4 D residues of 0.39 ppm 1 3 days after treatmen 0.4 ppm after 7 days, and 0.1 ppm after 14 days. Application at 8 lb ae/ A resulted in 2,4 D residues of 0.69 ppm days after treatment, 0.395 ppm after 7 days, and 0.013 ppm after 14 days. After 28 days following either treatment, residues were < 0.005 ppm. In another study, application of the DMA salt to two TVA reservoirs at 4 ae/ A resulted in residues of up to 1.2 ppm 1 hour post treatment, 4.8 ppm at 8 hours, 1.8 ppm at 24 hours, and 0.67, 0.24, and 0.018 ppm, respectively, at 2 weeks, 4 weeks, and 2 months after treatment. In a Bureau of Reclamation study, reservoir water treated with the DMA salt or butoxyethyl ester at 40 lb ae/ A had residues o to 0.22 ppm after 1 day, 0.09 ppm after 4 days, and 0.01 ppm after 14 days. Treatment of lakes in three states lb ae/ A, yielded samples containing 3.8 ppm of 2,4 D one day after treatment, 1.1 ppm after 4 days, and 0.052 p after 7 14 days, and at reservoir outlets, maximum residues were 0.015 ppm throughout the study. The 1992 review of the above data concluded that rates of up to 40 lb ae/ A could be extended to sites outside the TVA system, provided that use is restricted to Federal, State, or local agencies or applicators under their control. Official Agency oversight of this aquatic use was deemed necessary owing to the relatively high 2,4 D concentrations in water observed initially after treatment and the need to control treatment and subsequent w uses.

Irrigated Crops: The Residue Chemistry Chapter of the 2,4 D Reregistration Standard previously determined that residues of 2,4 D at up to 0.5 ppm are expected in irrigation water derived from 2,4 D treated ponds, lakes reservoirs. Citing the data from numerous studies on crops irrigated with 2,4 D treated water, the Agency tentatively concluded that tolerances for irrigated crops should be established at 1 ppm for crop groups and the individual miscellaneous crops. However, the aquatic use patterns currently being supported by the Task Force II prohibit the use of 2,4 D treated water for irrigation unless an approved assay indicates that 2,4 D concentrations are

0.1 ppm.

RAT METABOLISM APPENDIX 1: MARC BRIEFING DOCUMENT 32 From 5/ 8/ 03 L. Taylor memo/ DER ( TXR No. 0051543) re. rat and dog metabolism and pharmacokinetics:

EXECUTIVE SUMMARY: In a pharmacokinetics/ metabolism study ( MRID 45840901), ( 14C) 2,4 D [ 98%% a. i., lot # 45B; ( 14C) batch # 011022, specific radioactivity 9.206 MBq/ mg), ring labeled] was administered to 18 male and female Fischer strain rats [ CDF Crl: BR ( F 344)] and 4 per sex pure bred beagle dogs once via gavage at dose levels of 0, 5, and 50 mg/ kg.

There were no overt signs of toxicity in either species or sex at either dose level. Essentially all of the radiolab was recovered from the rats, while approximately half was recovered from the dogs [ dog carcasses were not monitored]. Plasma levels of radiolabel reached maximum concentration at 1hour [ low dose] and 2 hours [ hig dose] post dose in rats of both sexes. Maximum plasma concentrations of radiolabel in the dog were attained 5.5 hours [ males]/ 6.0 hours [ females] at the low dose and 8.0 hours [ males]/ 10 hours [ females] at the high dos both the rat and dog, clearance of radiolabel from plasma was slightly more prolonged in females than in mal both dose levels. In the rat, pharmacokinetic parameters were not linear with respect to dose level. A 10 fold increase in dose resulted in an  60 fold increase in AUC and an  20 fold increase in C max, suggesting that a clearance mechanism was saturated at the high dose level in the rat. In contrast, the pharmacokinetic parame in the dog were essentially proportional with the 10 fold increase in dose level, with a similar increase in both and C max.

The majority of the radiolabel was excreted in the urine of both male [ low  77%/ high  73%] and female [ low  73%/ high 57%] rats at both dose levels and both sexes of dogs at the low dose level [ males 35%/ females 36% Of the amount excreted via the urine, greater than 90% was excreted by 12 hours post dose in the low dose ra [ both sexes] and high dose male rats, while the high dose female rats excreted only 79% by 12 hours post do [ 96% by 24 hours post dose]. In the dog, of the amount excreted via the urine, less than 15% was excreted by hours post dose. Elimination of  80% of the dose via the urine by the dogs was not attained until 96 hours po dose in both sexes and both dose levels [ low males 84%/ females 83%; high males 80%/ females 84%]. Less tha 2.5% of the radiolabel was excreted in the feces of male rats at both dose levels, and the low dose female rats excreted  3.4% via the feces. High dose female rats excreted  8.4% via the feces. Of the amount of radiolabel excreted via the feces, the majority was excreted by 12 hours post dose in both the low [ 76%] and high [ 66% dose male rats. Of the amount of radiolabel excreted via the feces in the low dose females, only 9% was eliminated by 12 hours post dose; 83% was eliminated by the 24 hour timepoint. For the high dose female rat 52% was excreted by the 12 hour time point and 27% by the 24 hour time point. In the dogs, excretion via the feces occurred throughout the duration of the study. Low dose male [ 13.03%] and female [ 10.08%] dogs excre about half the amount of radiolabel via the feces as did the high dose male [ 25%] and female [ 21.27%] dogs. A 120 hours post dose, the amount eliminated via the feces [ both sexes] was 15% at the low dose and 11% [ males]/ 13% [ females] at the high dose. At the high dose level, the greatest amount excreted via the feces occurred at the 48 and 72 hour timepoints post dose in both sexes of the dog. At the low dose level, the grea amount excreted via the feces also occurred at the 48 and 72 hour timepoints post dose in the male dogs, wh comparable amounts [  20%] were excreted at the 24, 48, and 72 hour timepoints in the low dose females. Females of both sexes displayed a slower, more prolonged clearance from the plasma than the males, althoug the difference between the sexes was more pronounced in the rat than in the dog.

At the 50 mg/ kg dose level, clearance was clearly reduced [ males 41  g/ g/ females 21  g/ g] compared to the 5 mg/ kg dose level [ males 238  g/ g; females 88  g/ g] in both sexes of rat, suggesting that a clearance mechanis was saturated at the higher dose level in the rat. The dogs displayed comparable clearance at both dose level indicating that both dose levels saturated a clearance mechanism [ males 1.0  g/ g at low; 1.5  g/ g at high dos Metabolism was minimal in the rat, with 2,4 D being excreted in the urine basically unchanged. In the dog, numerous, minor, metabolites of 2,4 D were excreted in the urine, with the main metabolic route being by conjugation. The major components in the dog urine were the glycine conjugate and the parent compound. T other identified metabolites were the glutamic acid, serine, and taurine conjugates of 2,4 D, the sulphate and glucuronide conjugates of the de acetylated parent compound, and the cysteine conjugate of the de chlorina and de acetylated parent.

This metabolism/ pharmacokinetics study in the rat and dog is classified acceptable/ non guideline. The study designed specifically to ( 1) compare the rat and dog with respect to the excretion of 2,4 D and ( 2) address the APPENDIX 1: MARC BRIEFING DOCUMENT 33 issue of the relevancy of the dog data for risk assessment. As such, the study fulfilled its objectives. However did not satisfy the guideline requirement for a metabolism/ pharmacokinetics study [ OPPTS 870.7485, OECD 4 in rats [ and dogs]. It was classified non guideline because no tissues were monitored, other than plasma/ bloo and the carcass of the dogs was not monitored.

DRINKING WATER RESIDUE CHARACTERIZATION:

EFED RESPONSES TO MARC MEETING QUESTIONNAIRE In order to determine which degradates, if any, should be included in the human drinking water exposure assessment, please answer the following questions to the best of your ability and create tables using the for provided below.

1. What is the name of the pesticide and what uses are being considered in this assessment?

2,4 D is an herbicide used on a wide variety of crops. EECs from aquatic exposure modeling for terrestrial use 2,4 D was performed by modeling with PRZM/ EXAMS. Specific uses chosen for aquatic exposure modeling include sugarcane in Florida, turf in Florida and Pennsylvania, spring wheat in North Dakota, winter wheat in Oregon, corn in Illinois and California, sorghum in Kansas and Texas, soybean in Mississippi, pasture in Nor Carolina, apples in North Carolina, Oregon, and Pennsylvania, and filberts in Oregon. Although this only represents a portion of the crops for which 2,4 D has a labeled use, it does represent crops with higher application rates and crops which have a large percentage of their total acreage treated with 2,4 D. Some crop with large total acreage treated were also included as modeled scenarios. These crops were also chosen to represent a wide geographic area, thus encompassing a variety of environmental conditions. By encompassin crops with large percentages of acreage treated with 2,4 D and a large geographic area, some crops with lowe maximum application rates were also covered in the set of scenarios.

2. Briefly describe the environmental persistence of the pesticide. What are expected to be the major routes degradation in the environment ( e. g. aerobic soil metabolism, soil photolysis, etc)? What is the expected persistence in soil and water ( provide available half lives)?

2,4 D is non persistent ( t 1/ 2= 6.2 days) in terrestrial environments, moderately persistent ( t 1/ 2= 45 days) in aerobi aquatic environments, and highly persistent ( t 1/ 2= 231 days) in anaerobic terrestrial and aquatic environments 3. Briefly describe the expected mobility of the pesticide. Is the pesticide volatile? Does the pesticide bind s sediment strongly ( please provide Kd or Koc)?

Because 2,4 D will be anionic ( X COO H+) under most environmental conditions, it is expected to be highly m ( K oc= 41) in soil and aquatic environments.

4. Briefly describe the degradates of the pesticide. Identify major and minor degradates. Provide available information regarding degradate stability and mobility.

The 2,4 D degradates detected in the various fate studies were 1,2,4 benzenetriol, 2,4 dichlorophenol ( 2,4 DC 2,4 dichloroanisole ( 2,4 DCA), chlorohydroquinone ( CHQ), 4 chlorophenol, volatile organics, bound residues, carbon dioxide. See Tables 18 and 19 for chemical name, structure, and maximum percents of applied radioactivity contributed by each degradate in several environmental fate laboratory studies.

5. If possible, describe the effects of water treatment on the pesticide and degradates that may reach drinking water sources. APPENDIX 1: MARC BRIEFING DOCUMENT 34 EFED is in the process of evaluating whether there are treatment effects for 2,4 D or any of its degradates.

6. Provide any other pertinent information ( e. g. monitoring data).

Monitoring data considered in the assessment were the NAWQA groundwater and surface water database, USGS/ EPA reservoir monitoring database, National Drinking Water Contaminant Occurrence Database ( NCOD and STORET. A preliminary review of the databases was conducted to provide peak and median concentrati and is summarized in Table 17. A more extensive review of the data is presented in the sections which follow Additionally, the quality of data ( especially with STORET) needs to be evaluated for targeting pesticide use ar detection limits, and analytical recoveries.

The monitoring data indicates 2,4 D is detected in ground and surface water. Also, 2,4 D is detected in finish drinking water. Maximum concentrations of 2,4 D in surface source water and ambient ground water are 58 u and 14.8 ug/ l, respectively. The highest 2,4 D concentrations ( 20000 ug/ l) determined to be present in the preliminary analysis from the STORET database reflect the detection limit rather than actual concentrations. highest detection in STORET reported above the detection limit without qualification is 7500 ug/ l in groundwa however, this value is of questionable validity and is not recommeded for use in the risk assessment. The hig median 2,4 D concentration of 1.18 ug/ l was derived from finished water samples in the NCOD database. The highest TWM concentration was 1.45 ug/ l from the NAWQA data. It is important to note the maximum contam level ( MCL) for 2,4 D is 70 ug/ l.

Table 17: Preliminary Analysis of Available Monitoring Data Data Source Peak Concentration ( ug ae/ L) Median Concentration ( ug ae/ L) TWM Concentration ( ug ae/ L)

Groundwater NAWQA 14.8 0.035 NA NCOD ( finished) 8 0.87 NA STORET 7500* 0.1 NA Surface Water NAWQA 15 0.035 1.45 USGS/ EPA Reservoir Raw Water 0.414 0.077 0.15 Finish Water 0.634 0.077 0.12 NCOD ( finished) 58 1.18 NA STORET 330* 0.01 NA * Maximum values in STORET are not recommended for exposure estimates given uncertainty in data quality. Values rep are for comparison with model estimates and other monitoring data only.

7. Complete the table for the pesticide and degradates.

Table 18. Environmental Degradates of 2,4 D Acid APPENDIX 1: MARC BRIEFING DOCUMENT 2 % AR =% of applied radioactivity.

35 Confirmed Degradate Lab Results Max % AR2 ( Study) Chemical Structure 1,2,4 benzenetriol 37 ( aqueous photolysis at pH 7)

2,4 dichlorophenol ( 2,4 DCP) 3.5 ( aerobic soil) 33 ( anaerobic aquatic soil metabolism, water + sediment) 5 ( aerobic aquatic soil metabolism, sediment)

2,4 dichloroanisole ( 2,4 DCA) 2.8 ( aerobic soil)

chlorohydroquinone ( CHQ) 16 ( aerobic aquatic soil metabolism, water)

Bound residues 1.0 ( soil photolysis) 60 ( aerobic soil) 41 ( anaerobic aquatic metabolism) 39 ( aerobic aquatic metabolism)

Carbon Dioxide 25 ( aqueous photolysis) 5 ( soil photolysis) 50 ( aerobic soil) 31 ( anaerobic aquatic metabolism) 16 ( aerobic aquatic soil metabolism) APPENDIX 1: MARC BRIEFING DOCUMENT 36 Volatile compounds 4 chlorophenol 2,4 DCA 1.9 ( anaerobic aquatic metabolism) 1.9 ( anaerobic aquatic metabolism)

Table 19. Profiles of 2,4 D and Its Degradates from Several Environmental Fate Studies.

Confirmed Degradate Maximum % of Applied Radioactivity Aqueous/ soil photolysis ( two studies) Aerobic aquatic metabolism Anaerobic aquatic met. + volatile Aerobic soil metabolism 1,2,4 benzenetriol 37/       2,4 dichlorophenol   5 33 + 1.9 3.5 2,4 dichloroanisole       2.8 chlorohydroquinone   16     Carbon dioxide 25/ 5 16 31 + 0 50 4 chlorophenol     0 + 1.9   Bound residues   / 1.0 39 41 + 0 60 AQUATIC FIELD DISSIPATION STUDIES In order to determine the relative maximum observed concentrations of 2,4 D compared to those of the water soil degradates occurring in the " real world", EFED provided brief summaries of several aquatic field dissipat studies. These are summarized below. Note that 2 butoxyethanol and dimethylamine were not analyzed in th studies.

2,4 D BEE ( MRID 4425001):

NC Study 2,4 D BEE ( 40.4 ug/ L) parent compound 2,4 D ( 2,750 ug/ L) hydrolysis product of 2,4 D BEE 2,4 dichlorophenol ( 4.0 ug/ L) 4 chlorophenol ( 127 ug/ L) 4 chlorophenoxyacetic acid ( 122 ug/ L)

MN Study 2,4 D BEE ( 8.3 ug/ L) parent compound 2,4 D ( 109 ug/ L) hydrolysis product of 2,4 D BEE 4 chlorophenoxyacetic acid ( 4.2ug/ L)

WA Study 2,4 D BEE ( 8.3 ug/ L) parent compound 2,4 D ( 117 ug/ L) hydrolysis product of 2,4 D BEE APPENDIX 1: MARC BRIEFING DOCUMENT 37 O Cl Cl O O CH 3 CH 3 O Cl Cl OH O O Cl O H OH O Cl O Cl Cl OH O O H 2,4 D DMA:

SD Study ( MRID 43908302) 2,4 D ( 4,800 ug/ L) dissociation product of 2,4 D DMA 2,4 dichlorophenol ( 10.0 ug/ L) 4 chlorophenoxyacetic acid ( 5 ug/ L)

NC Study ( MRID 43954701) 2,4 D ( 2,800 ug/ L) dissociation product of 2,4 D DMA 2,4 dichlorophenol ( 6.0 ug/ L) 4 chlorophenol ( 3 ug/ L) 4 chlorophenoxyacetic acid ( 12 ug/ L)

LA Study ( MRID 43491601) 2,4 D ( 1,371 ug/ L) dissociation product of 2,4 D DMA Table 20. 2,4 D and its metabolites in plants.

Chemical Name Substrate MRID Structure Common Name 0 ( 2,4 dichlorophenoxy) acetic acid, 2 ethylhexyl ester wheat forage and straw 42439701 2,4 D IOE ( 2,4 dichlorophenoxy) acetic acid wheat forage, straw, and grain 42439701 2,4 D ( 4 hydroxy 2,5 dichlorophenoxy) acetic acid wheat forage and straw 42439701 42615601 4 OH 2,5 D ( 5 hydroxy 2,4 dichlorophenoxy) acetic acid wheat forage and straw 42439701 42615601 5 OH 2,4 D ( 4 hydroxy 2,3 dichlorophenoxy) acetic acid APPENDIX 1: MARC BRIEFING DOCUMENT Chemical Name Substrate MRID Structure Common Name 38 O Cl O H OH O Cl OH Cl Cl wheat forage and straw 42439701 42615601 4 OH 2,3 D 2,4 dichlorophenol wheat forage and straw 42439701 2,4 DCP