Page 1 of 17 **UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY** 

**WA SHINGTON, D.C. 20460**  **OFFICE OF CHEMICAL SAFETY**  **AND POLLUTION PREVENTION**  **MEMORANDUM D**  **ATE :**  01/23/14 **SUBJECT:** Zoxamide . Petition for the Establishment of Permanent To lerances fo r Use on

Dry Onion B ulbs . Summary of Anal ytical Chemistry

and Residue Data . **PC Code:** 101702 **DP Barcode:** D 416653 **Decision No.:** 476622 **Registration No. :**  10163 - 6414 **Petition No.:**  3F8164 **Regulatory Action:** Section 3 Registration **Risk Assessment Type:** NA **Case No.:** NA **T XR No.:**  NA **CAS No.:** 156052 - 68 - 5 **MRID No.:** 49067102 **40 CFR:** 180 . 567 **FROM:** Meheret Negussie , Chemist

Risk Assessment Branch III Health Effects Division (HED 7509P) **THROUGH:** Steve Funk , Senior Chemist

Christine Olinger , Branch Chief Risk Assessment Branch III Health Effects Division (HED 7509P) **TO:** Marcel Howard /Hope Johnson , RM#21 Fungicide Branch Registration Division (7505P)Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 2 of 17 **Executive Summary** Zoxamide is a broad - spectrum protectant fungicide registered for use on potatoes, grapes, tomatoes, and cucurbit vegetables. Tolerances for residues of zoxamide have been established under 40 CFR §180.567(a)(1) on grapes at 3.0 ppm, grape raisins at 15.0 ppm, tomatoes at 2.0 ppm, and cucurbit vegetables at 1.0 ppm. Tolerances are established under 40 CFR §180.567(a)(2) for the combined residues of zoxamide and its metabolites on potatoes at 0.06 ppm, potato flakes and chips at 0.30 ppm, and potato w et peel at 0.10 ppm. Gowan Company (Gowan) has submitted a petition for the establishment of permanent tolerances for the residues of zoxamide [3,5 - dichloro -N - (3 - chloro - 1 - ethyl - 1 - methyl - 2 - oxopropyl) - 4 - methylbenzamide and its metabolites 3,5 - dichloro - 4 - hydromethylbenzoic acid (RH - 1 452 ) and 2,6 - dichlorobenzene - 1,4 - dicarboxylic acid ( RH - 1453 ) in/on dry bulb onions . Section F of the current petition proposes the establishment of permanent tolerances for residues of zoxamide and its metabolites in/on: Dry bulb O nion (Crop Group 3, Bulb Vegetables ) ......................... 0.7 ppm In conjunction with this petition, Gowan is requesting amended registration of the 75% water dispersible granule (WD G) formulation of zoxamide (Gavel® 75DF Fungicide ) (EPA Reg. No. 10163 - 6414 ) , to add uses on dry bulb onions. Gavel 75 DF agricultural f ungicide is a mixture of 8.3% zoxamide and 66.7% mancozeb. Onl y z oxamide is evaluated in this assessment. The product is proposed for up to eight foliar applications at 0.12

–0.17 lb ai/A/applic ation for a total seasonal application rate of 1.33 lb ai/A, with a preharvest interval (PHI) of 7 days. Adequate metabolism studies on potatoes, grapes, cucumbers, and tomatoes are available. The residue of concern for tolerance setting and risk assessment is zoxamide for grapes, grape processed commodities, tomatoes, and cucumbers . The residue of concern for tolerance setting and risk assessment is zoxamide and its metabolites (RH - 1452 and RH - 1455) in/on potatoes and processed potatoes . There are no livestock feed items associated with this petition. Adequate anal ytical methods are available for enforcing zoxamide tolerances and collecting data on residues in plant commodities. The anal ytical methods , gas chromatography with electron capture detection (GC/ECD) and GC with mass selective detection (GC/MSD ) are available for tolerance enforcement for plant commodities as primary and co nfirmatory

methods, respectivel y. For the acid metabolites ( RH - 1452 and RH - 1455 ), the GC/MSD is the primary method and the GC/ECD method is the confirmatory method. The methods have been adequatel y validated for the determination of residues of zoxamide in plant commodities . Samples from the submitted crop fiel d trials were anal yz ed for residues of zoxamide and its metabolites using an acceptable GC/MSD method. The method w as adequately validated prior to and /or in conjunction with the anal ys is of the field trial samples. The validated limit of quantitation ( LO Q ) was 0.0 2 ppm for each anal yt e in dry bulb onion.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 3 of 17 Adequate multiresidue methods testing data have been submitted. The data indicate that t he multiresidue methods are adequate for enforcement of tolerances for zoxamide only . Adequate storage stability data are available to support storage conditions and intervals of samples from the onion bulb crop field trials . The submitted crop field trial data for dry onion bulb reflect the proposed use pattern and are acceptable . The submitted data will support the proposed tolerances for dry onion bulb of 0.7 ppm . Using the Organization of Economic Cooperation and Development (OECD) statistical calculation procedure , the recommended tolerance for onion bulb is 0.7 ppm , which is the s ame as the proposed tolerance . H ED recommends submitting a revised Section F to propose a tolerance on onion, bulb, subgroup 3 - 07A. The nature of the residue in rotation al crops is understood based on adequat e confined rotational crop studies . HED has concluded that the residues of concern for rotational crops for risk assessment and tolerance setting purposes are the parent compound, and its metabolites RH - 1455 and RH - 1452. The available data support the 30 - day plant - back interval (PBI) specified on the label for rotated crops without primary uses of zoxamide. There are no Codex or Canadian maximum residue limits (MRL s) established for residues of zoxamide in/on onion bulbs. The U S tolerance and Canadian MRLexpressions are the same. The US and Canadian residue definitions include zoxamide for grapes and processed grapes and zoxamide and its metabolites for potatoes and processed potatoes . The US and Codex residue definitions are not in harmony . The Codex residue definition includes only zoxamide for all crops. An International Residue Limit Status sheet is attached (Attachment II) **Regulatory Recommendations and Residue Chemistry Deficiencies** HED has examined the residue chemistry database for zoxamide . Pending submission of revis ed Sections B and F and submittal of analy tic al standard, there are no residue chemistry issues that would preclude granting registration for the requested uses of zoxamide on dry bulb onion or establishment of the following tolerances for combined residues of zoxamide and its metabolites: 40 CFR §180.567 (a) (2 ):

Onion, bulb, subgroup 3 - 07A ................................ ....... 0.7 ppm A human health risk assessment is forthcoming. **Note to PM: According to HED’s Interim Guida nce on Tolerance Expressions (5/27/09, S**  **. Knizner), the tolerance expressions for**  **zoxamide should be revised as follow:**  **Under 40 CFR §180. 567**  **(a) (1): “Tolerances are established for residues of**  **zoxamide including is metabolites and degradates, in or on the commodities in the table below.**  **Compliance with the tolerance levels specified below is to be determined by measuring only zoxamide**  **( 3,5**  **- dichloro**  **- N**  **- (3**  **- chloro**  **- 1**  **- ethyl**  **- 1**  **- methyl** **- 2**  **- oxopropyl)**  **- 4**  **- methylbenzamide**  **) .**  **Under 40 CFR §180.567 (a)**  **(2): “Tolerances are established for residues of zoxamide**  **including is metabolites and degradates, in or on the commodities in the table below.**Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 4 of 17 **Compliance with the to lerance levels specified below is to be determined by measuring only**  **the sum of zoxamide (** **3,5 -**  **dichloro -** **N -**  **(3 -**  **chloro -**  **1 -**  **ethyl -**  **1 -**  **methyl -**  **2 -**  **oxopropyl) -**  **4 -**  **methylbenzamide )**  **and its metabolites 3,5 -**  **dichloro -**  **1,4 -**  **benzenedicarboxylic acid (RH -**  **1455 and RH**  **- 141455) and 3,**  **5 -**  **dichloro -**  **4 -**  **hydroxymethylbenzoic acid (RH -**  **1452 and RH -**  **141452) calculated as the stoichiometric equivalent of**  **zoxamide.** 860.1200 Directions for Use

 The proposed use directions for onions (dry bulb), garlic, and shallots should be revised to onions (dry bulb), garlic, and shallot bulb s . 860.1550 Proposed Tolerances

 The proposed tolerance of 0. 7 0 ppm for “Dry bulb Onion (Crop Group 3, Bulb Vegetables)” should be revised to O nion, bulb, subgroup 3 - 07A at 0.7 ppm . 860.1650 Submittal of Analy tical Reference Standards

 The anal ytical reference standard for zoxamide is depleted . A 5g standard needs to be supplied to the repository. **Background** The chemical names and structures of zoxamide and the acid metabolites RH - 1452 and RH - 1455 are presented in Table 1. The physicochemical properties of the technical grade of zoxamide are presented in Table 2 . **Table 1**  **. Zo**  **xamide Nomenclature.**  Chemical structure

Common name Zoxamide Company experimental name RH - 7281 IUPAC name (RS ) - 3,5 - dichloro -N

- (3 - chloro - 1 - ethyl - 1 - methyl - 2 - oxopropyl) - p - toluamide Molecular weight 336.64 g/mol CAS name 3,5 - dichloro -N - (3 - chloro - 1 - ethyl - 1 - methyl - 2 - oxopropyl) - 4 - methylbenzamide CAS registry number 156052 - 68 - 5 End -use product (EP) Gavel ® 75DF Fungicide (EPA Reg. No. 10163 - 6414 ) (This product is a combination of zoxamide + mancozeb. Only zoxamide residues have been determined.) N H Cl

Cl Cl

O

OZoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 5 of 17 **Table 1**  **. Zo**  **xamide Nomenclature.**  Chemical structure

Common name RH - 141452 Company experimental name RH - 1452 Chemical name 3,5 - dichloro - 4 - hydromethylbenzoic acid Molecular weight 221.04 g/mol CAS Name Not available Chemical structure

Common name RH - 141455 Company experimental name RH - 1455 Chemical name 2,6 - dichlorobenzene - 1,4 - dicarboxylic acid Molecular weight 235.02 g/mol CAS Name Not available **Table 2. Physicochem** **ical Properties of Zoxam** **ide .** 

**Parameter Value**  **Reference** Melting point/range 159.5 - 160.5 ° C (98.8% purity) MRID 49067102 pH Density Relative Density 1.38 at 20 ° C Water solubility (at 2 0 °C) 0.681 ± 0.017 mg/L Solvent solubility (at 2 0 °C) Ethyl acetate: 20.0 g/L Acetone: 55.7 g/L Xylene: 1.56 g/L n - Octanol: 6.49 g/L n - Heptane: 0.038 g/L 1,2 - Dichloroethane: 12.5 g/L Vapor pressure (at 25 , 35, and 45 °C) <1.3 x 10 - 5 Pa Dissociation constant, pKa Not measurable by spectrophotometry, titration or conductivity. Absorbance did not change in acidic, neutral, or basic conditions; Solubility was too low for titration; with decrease in concentration, no increase in reading was observed . O ctanol/water partition coefficient, KOW Log Kow 3.76 ± 0.04 at ambient temp UV/visible absorption spectrum 212 nm. ε = 46330Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 6 of 17 **860.1200 Directions for Use** Gowan has submitted proposed use directions (Section B) for the 75% water dispersible granule (WG) formulation of zoxamide (Gavel® 75DF Fungicide ) (EPA Reg. No. 10163 - 6414 ) on dry bulb onions. Gavel 75 DF agricultural f ungicide is a mixture of 8.3% zoxamide and 66.7% mancozeb. The proposed use directions for onion bulb are presented in Table 3. **Table 3**  **. Summary of Directions for Use of**  **Zo xamide**  Applic. Timing, T ype, and Equip. Form

ulation 1 [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Season Max.

Seasonal Applic. Rate (lb ai/A) PHI 1

(days) Use Directions and Limitations 2

Onions (dry bulb) , garlic, and shallots Broadcast, Foliar, Ground, aerial, or chemigation (Gavel®

75DF Fungicide [ 10163 - 6414 ] 0. 12 - 0.1 7

1.5 to 2.0 (product) 8 1.33 7 Follow a protective spray schedule starting when diseases are first reported in the area and repeat at 7 - day intervals throughout the season . Do not allow

spray or drift to contact bulbs after lifting from soil. Do not apply to exposed bulb. 1 PHI = Pre - harvest interval For ground applications on potatoes, cucurbits, tomatoes , and dry bulb onions , the label recommends a spray

volume of 2 - 3 gal/A; and 5 gal for vineyards. The label specifies application in a minimum of 2 gallons of water per acre (GPA) using aerial equipment; in the state of CA a minimum of 5 GPA should be used. Chemigation applications are to be made through sprinkler- ty

pe irrigation s ys tems only . The label recommend s using agricultural surfactants and that zoxamide can be tank mixed with other registered fungicides. The following crop restrictions a

ppear on the registered label: 0 - day PBI fo r any crop listed on the label and 30 - day PBI for all other crops . Note: The Section B/label must be revised to indicate use on onion s (dry bulb ), garlic, and shal lot, bulb s . Conclusions . The submitted use directions are adequate to allow evaluation of the residue data relative to the proposed use. The submitted field trial data for onion bulb reflect the maximum proposed use rates , the minimum retreatment intervals (RTI s), and the proposed PHI s.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 7 of 17 **860.1300 Nature of the Residue**  **- Plants**  Residue Chemistry Memo DP# 237892 , 1/10/2001 , A. Acierto Residue Chemistry Memo DP# s 266181 , D268774 , 4 /02 /200 1 , A. Acierto A dequate metabolism studies on potatoes, grapes, cucumbers, and tomatoes are available. The HED’s Metabolism Assessment Review Committee (MARC) has determined that the residue of concern for tolerance setting and risk assessment is zoxamide for grapes and grape processed commodities and is zoxamide and its metabolites (RH - 1452 and RH - 1455) in/on potatoes (Memo, A.M. Acierto & W.D. Wassell, 12/18/2000, D270797). The data concerning the metabolism of zoxamide in/on tomatoes and cucumbers were not p resented to the MARC and HED had concluded the residue of concern in tomatoes and cucurbit vegetables for tolerances and risk assessment is zoxamide. The nature of the residue of zoxamide on bulb onions is understood based on available metabolism studies. **860.1300 Nature of the Residue -**  **Livestock** Residue Chemistry Memo DP# D277097 , 12/18/2000 , A. Acierto Residue Chemistry Memo DP# 237892 , 1/10/2001 , W. Wassell , A. Ac ierto An acceptable metabolism study on goats is available. The MARC did not determine the residue of concern in ruminants since HED has concluded that livestock tolerances are not needed at this time. HED has concluded that tolerances for secondary residues in milk and ruminant tissues are not required at this time and the uses can be considered category 3 of 40 CFR §180.6(a). It is not possible to determine with certainty whether finite residues will be incurred, but there is no reasonable expectation of finite residues in milk and ruminant tissues. Poultry : A poultry metabolism study

has not been submitted. There are no poultry feed items associated with the registered/

proposed uses of zoxamide. Therefore, a poultry metabolism study

is not required. However, if any crops which have poultry feed items are added in the future, then a poultry metabolism study will be required. **860.1340 Residue Analytical Methods** Residue Chemistry Memo DP# 237892 , 1/10/2001, A. Acierto Residue Chemistry Memo DP#s 266181, D268774 , 4/02/2001, A. Acierto Plant commodity

methods Enforcement m ethod: A gas chromatography using electron capture detection (GC/ECD) as the primary method and a GC with mass selective detection (GC/MSD ) as the confirmatory method are available for tolerance enforcement for plant commodities.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 8 of 17 Adequate method validation, radiovalidation, and independent method validation has been submitted for the primary and confirmatory method s . For the two acid metabolites, RH - 1452 and RH - 1455, in/on potato tubers and potato processed fractions, the GC/MSD method is proposed as the primary method and the GC/ECD method as the confirmatory

method. The GC/ECD and GC/MSD methods were validated by the Anal ytical Chemistry Branch (ACB)/Biological and Economic Analysis Division (BEAD) . After validation by ACB, th e enforcement methods were forwarded to FDA. (DP# D284394, D284396, D284398, and D28400). Data collection methods: Samples of dry bulb onions from the submitted crop field trials were anal yz ed for residues of zoxamide and its two acid metabolites (RH - 1452 and RH - 1455) using an acceptable GC/MSD method . The method was adequatel y validated prior to and/or in c onjunction with the analysis of the field trial. The validated LOQs were 0.0 2 ppm for each anal yt e. Briefl y, residues in homogenized samples were extracted with acetonitrile (ACN): 2% sodium carbonate (80:20, v:v) and filtered. The filtrates are combined and concentrated. Residues in the concentrated extract are partitioned with 2% sodium carbonate solution and ethyl acetate (16:15, v:v). The aqueous layer containing the sodium salts of RH - 1452 and RH - 1455 was re partitioned with ethyl acetate. The organic layers were combined and concentrated to dry ness. Residues were re - dissolved in hexane , sonicated , then subjected to Florisil solid phase extraction (SPE). Residues of zoxamide were eluted with hexane:ethyl acetate (80:20 , v:v), concentrated to dry ness, and re - dissolved in hexane for further purification by Alumina - B SPE. Zoxamide residues were eluted with hexane:ethyl acetate (80:20, v:v), concentrated to dry ness, re - dissolved in ethyl acetate, and sonicated for anal ys is by GC/MSD . For the aqueous layer , following liquid - liquid partitioning and after adjusting the pH to ≤1 , residues were partitioned with ethyl acetate. The aqueous layer was re -partitioned with ethyl acetate; the remaining aqueous layer was discarded, an d the organic layers were combined with sodium sulfate. The solution was decanted, concentrated to dry ness, re - dissolved in ethyl acetate, sonicated, and ethyl ether was added. Residues of RH - 1452 and RH - 1455 were methylated with diazomethane. The acid metabolites were esterified. The methylated residues of RH - 1452 (RH - 7391) and RH - 1455 (RH - 7399) are concentrated to dry ness and re - dissolved in hexane for further purification by Florisil column chromatography. Residues were eluted with ethyl acetate, co ncentrated to dry ness, and re - dissolved in ethyl acetate for analysis. Residues of RH - 7391 and RH - 7399, methylated residue of the acid metabolites, were quantitated by GC/MSD. Livestock commodity

methods The petitioner is not proposing tolerances for zoxamide residues in milk, eggs, and animal tissues. Consequently , attempts to develop residue anal ytical methods for animal commodities were not pursued. HED has concluded that, based on the proposed uses, residue anal ytical methods for animal commodities are not required for this petition.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 9 of 17 Conclusions. The residue anal ytical methods for plants are adequate. Acceptable methods are available for tolerance enforcement purposes for the residues of concern in/on plant commodities, and samples of dry bulb onions from the submitted crop field trials were anal yz ed for residues of zoxamide and its metabolites using an acc eptable data collection method. **860.1360 Multiresidue Methods** Residue Chemistry Memo DP# 237 892 , 1/10/2001, A. Acierto The petitioner has previously submitted data pertaining to the multiresidue methods testing of zoxamide and its metabolites (RH - 1452 and RH - 1455) in conjunction with PP#9F05058. The multiresidue methods data indicate that zoxamide was successfully recovered using Protocols D and E, while none of the protocols successfull y recovered either of the metabolites. The MRMs are adequate for enforcement of zoxamide tolerances. The submission has been forwarded to FDA for complete evaluation in conjunction with the earlier petition (D255783, N. Dodd, 7/20/99). **860.1380 Storage Stability** Residue Chemistry Memo DP# 237892 , 1/10/2001, A. Acierto Based upon available data, residues of zoxamide in/on potatoes are stable during frozen storage for a period of 11.3 months. Based on the results of a successful radiovalidation study , residues of the acid metabolites in/on potato, tubers are stable under frozen storage conditions for up to 29 months. Potato crop field trial samples were stored frozen for a period of 12 to 23 months prior to analysis and potato processed commodities were stored frozen for a period of 12 months prior to analysis. Previousl y, a djustment of the potato processing data for storage degradation prior to anal ys is was not required. The storage duration s and conditions of samples from the submitted crop field trials are presented in Table 4 . **Table 4**  **. Summary of Storage Conditions and**  **Duration s of Samples from**  **Crop Field Trial and**

**Processing Studies.** Matrix Storage Tem perature (°C) Actual Storage Duration Interval of Demonstrated Storage Stability Dry bulb onions ~ - 25 - 10 40 - 343 days ( 1. 3 - 11. 4 mo nths) Residues of zoxamide are stable during frozen storage in/on potatoes f or up to 11.3 mo nths and its metabolites are stable up to 29 months. Conclusions . The available storage stability data for zoxamide on potatoes are adequate to support the storage durations and conditions of samples of dry bulb onion raw agricultural commodities from the submitted crop field trials.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 10 of 17 **860.1400 Water, Fish, and Irrigated Crops** This guideline requirement is not relevant to the current petitions as there are no aquatic uses currentl y proposed for zoxamide. **860.1460 Food Handling** This guideline requirement is not relevant to the current petitions as there are no food handling uses being proposed for zoxamide. **860.1480 Meat, Milk, Poultry, and Eggs**  There are no livestock feedstuffs associated with the proposed use of zoxamide on onion bulbs. **860.1500 Crop Field Trials** DER References: 4 9067102 .der .doc **Table 6 .**  **Summary of Residue Data from Dry Bulb Onion Crop**  **Field Trials with**  **Zoxamide.** Commodity Analyte Total Rate lb ai/A (kg ai/ha) PHI

(days) Residue Levels (ppm) 1 n Sample Min. Sample Max. LAF T 2 HAFT 2 Median Mean Std. Dev. Dry bulb onion Zoxamide 1.32 - 1.34 (1.48 - 1.51) 6 - 7 12 <0.02 0.443 <0.020 0.435 0.172 0.163 0.115 RH - 1455 12 <0.02 <0.02 <0.02 <0.02 0.02 0.02 N/A RH - 1452 12 <0.02 0.053 <0.02 0.049 0.023 0.028 0.010 Combined 12 <0.062 <0.483 <0.063 <0.475 0.221 0.211 0.113 1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. 2 LAF T = lowest average field trial; HAFT = highest average f ield trial. Onion bulb Gowan has submitted field trial data for zoxamide on dry bulb onion. Twelve field trials were conducted in the United States and Canada during the 2011 and 2012 growing seasons in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (NY; 1 trial), 5 (ON; 2 trials and MI, WI , and IA; 1 trial each), 6 (TX; 1 trial), 8 (KS ; 1 trial), 10 (CA; 2 trials), 11 (ID; 1 trial), and 12 (OR; 1 trial). Each trial consisted of one untreated plot and one treated plot. At each trial location, the treated plot received eight foliar broadcast applications of a 75% water dispersible granule (WG) formulation of zoxamide (Gavel® 75DF Fungicide ) at 0 .160 - 0.174 lb ai/A/application (0.179 - 0.195 kg ai/ha/application) for a total seasonal rate of 1.32 - 1.34 lb ai/A (1.48 - 1.51 kg ai/ha). Applications were made at 6 - to 8 - day retreatment intervals (RTIs). Applications were made using ground equipment in spray volumes of 15 - 39 gal/A (140 - 365 L/ha). A nonionic surfactant (NI S) was added to the spray mixture s at all trial sites . Samples of dry bulb onions were harvested at a 6 - to 7 - day preharvest interval (PHI). Additional dry bulb onion samples were harvested from one trial (MI ; TCI - 11 - 319 - 04) at PHI s of 0, 3, 10, and 14 days to assess residue decline. Samples were anal yz ed for residues of zoxamide and its acid metabolites RH - 14 5 2 and RH - 1455 using a gas chromatography method with mass selective detection (GC/MSD), entitledZoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 11 of 17 “Tolerance Enforcement Method for Parent RH - 7281 and it s Two Acid Metabolites, RH - 1452 and RH - 1455, in Potato Peel Waste , ” dated June 1, 2000 , with Morse Laboratories method mo difications dated June 25, 2012. The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.02 ppm for each analy te in dry bulb onion. The method was adequate for data collection based on acceptable method validation and concurrent recovery data. The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels. Quantifiable residues of RH - 1455 and RH - 1452 were converted to parent equivalents b y the petitioner using molecul ar weight conversion factors of 1.43 for RH 1455 and 1.52 for RH - 1452. Dry bulb onion samples were stored frozen (frozen at the field sites and - 25 to - 10 °C at the anal ytical laboratory) from collection to analysis for 40 - 343 days (1. 3 - 11. 4 months). Samples were anal yz ed within 0 - 9 days of extraction. Adequate storage stability data are available to support the storage durations and conditions of samples from the submitted field trials. Following eight foliar broadcast applications of the 75% WG formulation of zoxamide at 1.32 - 1.34 lb ai/A, residues (and per trial averages) of zoxamide, RH - 1452, and combined residues, respectivel y, in/on bulb onions harvested at a 6 - to 7 - day PHI were <0.02 - 0.4 4 3 (<0.020 - 0.435), <0.02 - 0.053 (<0.02 - 0.049), and <0.062 - <0.483 (<0.063 - <0.475) ppm; residues of RH - 1455 were <LOQ (0.02 ppm) in/on all samples of dry bulb onion. In the residue decline trial, average residues of zoxamide were 0.333, 0.339, 0.264, 0.293, and 0.167 ppm at the 0 - , 3 - , 7 - , 10 - , and 14 - d ay PHIs, respectivel y , indicating an overall decline in residues with increasing PHI s. Average residues of RH - 1452 as parent equivalents were 0.0266, 0.0309, 0.0263, <0.0260, and 0.0266 ppm at the 0 - , 3 - , 7 - , 10 - , and 14 - day PHI s, respectivel y , indicating that residues were fairl y stable over the sampling period. Residues of RH - 1455 were <LOQ in/on all samples; therefore, residue decline could not be assessed . Average combined residues were <0.379, <0.390, <0.310, <0.338, and <0.213 ppm at the 0 - , 3 - , 7 - , 10 - , and 14 - day PH Is , respectivel y, indicating a general o verall decline in residues with increasing PHIs . Conclusions . Provided the directions for use and the proposed tolerances are revised, the submitted onion bulb field trial studies are a cceptable and re flect the proposed use patterns. Samples were anal yz ed for residues of zoxamide and it is metabolites using acceptable methods, and the studies are supported by adequate storage stability data . The average field trial values for bulb onions were entered into the OECD spreadsheet to determine an appropriate tolerance level. Refer to Appendix Ifor the tolerance calculations. The OECD tolerance calculation procedure recommends a tolerance of 0. 7 ppm for dry bulb onions . The recommended tolerance level is the same as proposed by the petitioner. H ED recommends submitting a revised Section F to propose a tolerance on onion, bulb, subgroup 3 - 07A. **860.1520 Processed Food and Feed** HED does not require residue data for any processed commodities associated with dry onion bulbs . Therefore, data requirements for processed food and feed are not relevant to this tolerance petition.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 12 of 17 **860.1650 Submittal of Analytical Reference Standards** The anal ytical reference standard for zoxamide is depleted . A 5g standard needs to be supplied to the repository . Metabolites of z oxamide are currentl y available in the EPA National Pesticide Standards Repository

(personal communication with Theresa Cole, ACB, 12/12/13 ), with expiration dates of 03/01/2015 (RH - 12452) and 02/07/2015 (RH - 1455). The new standard should be sent to the Anal ytical Chemistry L ab (located at Fort Meade), to the attention of Theresa Cole, at the following address: USEPA National Pesticide St andards Repository /Anal ytical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 (Please note that the mail will be returned if the extended zip code is not used.) **860.1850 Confined Accumulation in Rotational Crops** Residue Chemistry Memo DP# 237892 , 1/10/2001, A. Acierto Residue Chemistry Memo DP#s 266181, D268774 , 4/02/20013, A. Acierto Acceptable confined rotational crop studies were reviewed in conjunction with PP#9F05058 on representative crops of mustard greens (leafy vegetable), radishes and turnips (root vegetable s ), sorghum and wheat (cereal grain s ) and so yb eans (legume/oil seed). The parent compound was not identified in any rotational crop commodity at any plantback interval. The metabolite RH - 1452 was tentativel y identified at <1 - 7% of TRR (ND - 0.011 ppm) except in 30 - day

PBI soybean forage where it accounted for 25% of TRR (0.023 ppm). Based on the results of the reviewed confined rotational crop study , it was concluded that there is no indication that zo xamide would be detected in rotational crops planted more than 30 days after the application of zoxamide. A 30 - day plant -back interval (PBI) specified on the label for rotated crops without primary uses of zoxamide is ade quate. **860.1900 Field Accumulation in Rotational Crops**  Residue Chemistry Memo DP# 237892 , 1/10/2001, A. Acierto Residue Chemistry Memo DP#s 266181, D268774 , 4/02/2001 , A. Acierto Based on the results of the reviewed confined rotational crop study and the data requirements specified in OPPTS 860.1850 , field accumulation studies are not required. **860.1550 Proposed Tolerances** Tolerances for residues of zoxamide have been established under 40 CFR §180.567(a)(1) on grapes at 3.0 ppm, grape raisins at 15.0 ppm, tomatoes at 2.0 ppm, and cucurbit vegetables at 1.0 ppm. Tolerances are established under 40 CFR §180.567(a)(2) for the combined residues ofZoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 13 of 17 zoxamide and its metabolites on potatoes at 0.06 ppm, potato flakes and chips at 0.30 ppm, and potato wet peel at 0.10 ppm. The OECD tolerance calculation procedure was utilized in determining appropriate tolerance levels for dry

bulb onions. Based on the tolerance spreadsheet, the proposed tolerance of 0.7 ppm for dry

bulb onion is appropriate. The tolerance proposed b y Gowan is listed in Table 10, along with the tolerance levels and revised commodity definitions recommended by HED . Pending submission of revised section s B and F , and submittal of analy tical standard, adequate field trial data reflecting the proposed use patterns are available for purposes of establishing tolerances on dry

bulb onions. **Note to PM: According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner), the tolerance expressions for**  **zoxamide should be revised as follow:**  **Under 40 CFR §180.567(a) (1): “Tolerances are established for residues of zoxamide**  **including is metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only**  **zoxamide (** **3,5 -**  **dichl oro**  **- N**  **- (3**  **- chloro**  **- 1**  **- ethyl**  **- 1**  **- methyl** **- 2**  **- oxopropyl)**  **- 4**  **- methylbenzamide**  **). Under 40 CFR §180.567 (a)**  **(2): “Tolerances are established for residues of zoxamide including is metabolites and degradates, in or on the commodities in the table below.**  **Compliance with the tolerance levels specified below is to be determined by measuring only the sum of zoxamide**  **( 3,5**  **- dichloro**  **- N**  **- (3**  **- chloro**  **- 1**  **- ethyl**  **- 1**  **- methyl** **- 2**  **- oxopropyl)**  **- 4**  **- methylbenzamide** **) and its metabolites 3,5**  **- dichloro**  **- 1,4**  **- benzenedicarboxylic acid (RH**  **- 1455**  **and RH -**  **141455) and 3,5 -**  **dichloro -**  **4 -**  **hydroxymethylbenzoic acid (RH -**  **1452 and RH -**  **141452) calculated as the stoichi**  **ometric equivalent of zoxamide. Table**  **10 .**  **Tolerance Summary for zoxam** **ide.** Commodity Tolerance (ppm) Comments; Correct Commodity Definition Proposed Recommended 40 CFR §180.609(a)( 2 ) O nion , bulb 0.7 0.7 Onion, bulb, subgroup 3 - 07A **References** DP#: 2 77097 Subject: PP#9F05058; Zoxamide in/on Potato and Grapes. Conclusions of the 11/14/2000

Meeting of the Metabolism Assessment Review Committee **.** From: A. Acierto To: G. Kramer Dated: 12/18/2000 DP#s: 237892 Subject: PP#9F05058. Zoxamide in/on Grapes and Potatoes . Review of Anal ytical

Methods and Residue Data. First Food Use Review.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 14 of 17 From: A. Acierto To: Rose Kearns/C ynthia Giles - Parker Dated: 1/10 /20 01 DP#s: 266181 and 268774 Subject: PP#0F06093. Zoxamide in/onTomatoes and Cucurbits . Review of Anal ytical

Methods and Residue Data. From: A. Acierto To: Rose Kearns/C ynthia Giles - Parker Dated: 4/2/2001 MRIDs: 45012103 to 45012118 DP#: 276323 Subject: PP# 9F05058. ID# 000707 - 00271 & ID# 000707 - 00272: Zoxamide in/on Grapes

and Potatoes. From: A. Acierto To: Rose Kearns/C ynthia Giles - Parker Dated: 5/10/2003 MRIDs: 45437802, 45499801, 45461402, and 45461403 Attachments: International Residue Limit Status sheet Appendix I - Tolerance Assessment Calculations Template Version April 200 8 

### International Residue Limits

Zoxamide (PC Code 101702 ; 12/04/2013 ) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3 40 CFR 180. 567 (a)General (1) 3,5 - dichloro -N

- (3 - chloro - 1 - ethyl 1 - methyl - 2 - oxopropyl) - 4 - methylbenzamide (2) combined residues of zoxamide and its metabolites 3,5 - dichloro - 1,4 - benzenedicarboxylic acid (RH - 1455 and RH - 141455) and 3,5 - dichloro - 4 - hydroxymethylbenzoic acid (RH - 1452 and RH - 141452) Grapes and raisins: 3,5 - dichloro -N - (3 - chloro - 1 - ethyl - 1 - methyl - 2 - oxopropyl) - 4 - methylbenzamide Potatoes, potato processed fractions (chips, flakes and granules): 3,5 - dichloro -N

- (3 - chloro - 1 - ethyl - 1 - methyl - 2 - oxopropyl) - 4 - methylbenzamide, including the metabolites 3,5 - dichloro - 1,4 - benzene - dicarboxylic acid and 3,5 - dichloro - 4 - hydroxymethyl benzoic acid ZoxamideZoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 15 of 17 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3 Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex 3 Onion, bulb, subgroup 3 - 07A 0.7

Com pleted: M. Negussie; 12/04/2013 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

**Appendix I. Tolerance Assessment Calculations.** The OECD statistical calculation procedure was used for calculating recommended tolerance on onion bulb . As specified in the OECD document, the average residue value from each field trial was used . Onion Bulb The dataset used to establish tolerance s for zoxamide and its metabolites consisted of field trial data representing appl ication rates of 1.3 2 - 1.34 lb ai/A ( 8 applications at 0.1 6 - 0.1 7 lb ai/A/application) with a 6 - to 8 - day PHI. The field trials reflect the proposed application rate and samples were collected at the proposed pre - harvest intervals. The residue values entered into the tolerance spreadsheet are provided in Table I - 1.Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 16 of 17 Using the OECD statistical calculation procedure the recommended tolerance for onion bulb is 0.7 ppm . **Table I -**  **1 .**  **Residue data used to calculate tolerance s**  **for zoxam** **ide on**  **onion bulb .**  **Regulator:** EPA **Chemical:** Zoxamide **Crop:** Onion bulb **PHI:** 6 - 8 days **App. Rate:** 1.3 2 - 1.34 lb ai/A **Submitter:** Gowan **MRID Citation:** MRID 49067102 **Combined r esidues of**  **zoxamide and its metabolites** 

0.218 0.475 0.261 0.310 0.244 0.063 0.140 0.073 0.128 0.160 0.242 0.223

**Figure I -**  **1 .**  **Tolerance s preadsheet summary of zoxam** **ide field trial data for dry onion bulb.**  **Zoxamide Dry,onion bulb**  **EPA 1.32**  **- 1.34 lb ai/A**  **Total number of data (n)** 12 **Percentage of censored data** 0% **Number of non -**  **censored data** 12 **Lowest residue** 0.063 **Highest residue** 0.475 **Median residue** 0.221 **Mean** 0.211 **Standard deviation (SD)** 0.113Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

Page 17 of 17 **Correction factor for censoring (CF)** 1.000 **Proposed MRL estimate**

**- Highest residue**  0.475

**- Mean + 4 SD**  0.662

**- CF x 3 Mean**  0.634 **Unrounded MRL** 0.662 **Rounded MRL 0.7**