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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION

MEMORANDUM

DATE: 01/23/14

SUBJECT: Zoxamide. Petition for the Establishment of Permanent Tolerances for Use on 

Dry Onion Bulbs. Summary of Analytical Chemistry and Residue Data.

PC Code: 101702 DP Barcode: D416653

Decision No.: 476622 Registration No.: 10163-6414

Petition No.: 3F8164 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case No.: NA

TXR 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

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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 wet 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-1452) 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 Onion (Crop Group 3, Bulb Vegetables) .........................0.7 ppm

In conjunction with this petition, Gowan is requesting amended registration of the 75% water 

dispersible granule (WDG) formulation of zoxamide (Gavel® 75DF Fungicide) (EPA Reg. No. 

10163-6414), to add uses on dry bulb onions. Gavel 75 DF agricultural fungicide is a mixture of 

8.3% zoxamide and 66.7% mancozeb. Only zoxamide is evaluated in this assessment. The 

product is proposed for up to eight foliar applications at 0.12–0.17 lb ai/A/application 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 analytical methods are available for enforcing zoxamide tolerances and collecting data 

on residues in plant commodities. The analytical 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 confirmatory methods, respectively. 

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 adequately validated for the determination of residues of zoxamide in 

plant commodities.

Samples from the submitted crop field trials were analyzed for residues of zoxamide and its 

metabolites using an acceptable GC/MSD method. The method was adequately validated prior 

to and/or in conjunction with the analysis of the field trial samples. The validated limit of 

quantitation (LOQ) was 0.02 ppm for each analyte in dry bulb onion. 
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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Adequate multiresidue methods testing data have been submitted. The data indicate that the 

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 same 

as the proposed tolerance. HED recommends submitting a revised Section F to propose a 

tolerance on onion, bulb, subgroup 3-07A. 

The nature of the residue in rotational crops is understood based on adequate 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 (MRLs) established for residues of 

zoxamide in/on onion bulbs. The US tolerance and Canadian MRL expressions 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 revised 

Sections B and F and submittal of analytical 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 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-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

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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 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 bulbs. 

860.1550 Proposed Tolerances

 The proposed tolerance of 0.70 ppm for “Dry bulb Onion (Crop Group 3, Bulb 

Vegetables)” should be revised to Onion, bulb, subgroup 3-07A at 0.7 ppm.

860.1650 Submittal of Analytical Reference Standards

 The analytical 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. Zoxamide 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

O
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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Table 1. Zoxamide 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. Physicochemical Properties of Zoxamide.

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 20°C) 0.681 ± 0.017 mg/L

Solvent solubility (at 20°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 10-5Pa

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.

Octanol/water partition coefficient, 

KOW

Log Kow 3.76 ± 0.04 at ambient temp

UV/visible absorption spectrum 212 nm. ε = 46330
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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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 fungicide 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 Zoxamide

Applic. 

Timing, Type, 

and Equip.

Formulation1

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI1

(days)

Use Directions and Limitations2

Onions (dry bulb), garlic, and shallots

Broadcast, 

Foliar, 

Ground, 

aerial, or 

chemigation

(Gavel® 

75DF 

Fungicide

[10163-6414]

0.12-0.17

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-type irrigation systems only. The label recommends using agricultural 

surfactants and that zoxamide can be tank mixed with other registered fungicides. The following 

crop restrictions appear on the registered label: 0-day PBI for 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 onions (dry bulb), garlic, and

shallot, bulbs. 

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 (RTIs), and the proposed PHIs.
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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860.1300 Nature of the Residue - Plants

Residue Chemistry Memo DP# 237892, 1/10/2001, A. Acierto

Residue Chemistry Memo DP#s 266181, D268774, 4/02/2001, A. Acierto 

Adequate 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 

presented 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. Acierto

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 method: 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

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Adequate method validation, radiovalidation, and independent method validation has been 

submitted for the primary and confirmatory methods.

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 Analytical Chemistry Branch 

(ACB)/Biological and Economic Analysis Division (BEAD). After validation by ACB, the 

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

analyzed for residues of zoxamide and its two acid metabolites (RH-1452 and RH-1455) using

an acceptable GC/MSD method. The method was adequately validated prior to and/or in 

conjunction with the analysis of the field trial. The validated LOQs were 0.02 ppm for each

analyte.

Briefly, 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 repartitioned with ethyl acetate. The organic layers were combined and concentrated to dryness. 

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 

dryness, 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 dryness, re-dissolved 

in ethyl acetate, and sonicated for analysis 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, and the organic layers were combined with 

sodium sulfate. The solution was decanted, concentrated to dryness, 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 dryness and re-dissolved in 

hexane for further purification by Florisil column chromatography. Residues were eluted with 

ethyl acetate, concentrated to dryness, 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 analytical methods for animal commodities 

were not pursued. HED has concluded that, based on the proposed uses, residue analytical 

methods for animal commodities are not required for this petition.
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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Conclusions. The residue analytical 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 analyzed 

for residues of zoxamide and its metabolites using an acceptable data collection method.

860.1360 Multiresidue Methods

Residue Chemistry Memo DP# 237892, 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 successfully 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. Previously, adjustment of the potato processing data for storage degradation prior to 

analysis was not required.

The storage durations and conditions of samples from the submitted crop field trials are 

presented in Table 4.

Table 4. Summary of Storage Conditions and Durations of Samples from Crop Field Trial and

Processing Studies. 

Matrix Storage

Temperature

(°C)

Actual Storage Duration Interval of Demonstrated Storage 

Stability

Dry bulb onions ~-25-10 40-343 days ( 1.3-11.4 months)

Residues of zoxamide are stable 

during frozen storage in/on 

potatoes for up to 11.3 months

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

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860.1400 Water, Fish, and Irrigated Crops

This guideline requirement is not relevant to the current petitions as there are no aquatic uses 

currently 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: 49067102.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.

LAFT

2 HAFT2 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

 LAFT = lowest average field trial; HAFT = highest average field 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 

(NIS) was added to the spray mixtures 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 PHIs of 0, 3, 10, and 14 days to assess residue 

decline.

Samples were analyzed for residues of zoxamide and its acid metabolites RH-1452 and RH-1455 

using a gas chromatography method with mass selective detection (GC/MSD), entitled 
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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“Tolerance Enforcement Method for Parent RH-7281 and its Two Acid Metabolites, RH-1452 

and RH-1455, in Potato Peel Waste,” dated June 1, 2000, with Morse Laboratories method 

modifications dated June 25, 2012. The limit of quantitation (LOQ; determined as the lowest 

level of method validation, LLMV) was 0.02 ppm for each analyte 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 by the petitioner using molecular weight conversion factors of 1.43 for RH1455 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 

analytical laboratory) from collection to analysis for 40-343 days (1.3-11.4 months). Samples 

were analyzed 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, 

respectively, in/on bulb onions harvested at a 6- to 7-day PHI were <0.02-0.443 (<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-day PHIs, respectively, indicating an overall decline in 

residues with increasing PHIs. 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 PHIs, respectively,

indicating that residues were fairly 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

PHIs, respectively, indicating a general overall 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 acceptable and reflect the proposed use patterns. 

Samples were analyzed 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 I for 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. HED 

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

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860.1650 Submittal of Analytical Reference Standards

The analytical reference standard for zoxamide is depleted. A 5g standard needs to be supplied 

to the repository. Metabolites of zoxamide are currently 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 Analytical Chemistry Lab (located at Fort Meade), to the 

attention of Theresa Cole, at the following address:

USEPA

National Pesticide Standards Repository/Analytical 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 vegetables), 

sorghum and wheat (cereal grains) and soybeans (legume/oil seed).

The parent compound was not identified in any rotational crop commodity at any plantback

interval. The metabolite RH-1452 was tentatively 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 zoxamide 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 adequate.

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 of 
Zoxamide 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 by Gowan is listed in Table 10, 

along with the tolerance levels and revised commodity definitions recommended by HED. 

 

Pending submission of revised sections B and F, and submittal of analytical 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-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. 

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 stoichiometric equivalent of zoxamide.

Table 10. Tolerance Summary for zoxamide.

Commodity Tolerance (ppm) Comments; Correct Commodity 

Definition Proposed Recommended

40 CFR §180.609(a)(2)

Onion, bulb 0.7 0.7 Onion, bulb, subgroup 3-07A

References

DP#: 277097

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 Analytical 

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/Cynthia Giles-Parker

Dated: 1/10/2001

DP#s: 266181 and 268774

Subject: PP#0F06093. Zoxamide in/onTomatoes and Cucurbits. Review of Analytical 

Methods and Residue Data.

From: A. Acierto

To: Rose Kearns/Cynthia 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/Cynthia 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 2008

International Residue Limits 

Zoxamide (PC Code 101702; 12/04/2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180. 567 (a)General 

(1) 3,5-dichloro-N-(3-chloro-1-ethyl1-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

Zoxamide
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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Onion, bulb, subgroup 3-

07A 0.7

Completed: 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 tolerances for zoxamide and its metabolites consisted of field trial 

data representing application rates of 1.32-1.34 lb ai/A (8 applications at 0.16-0.17 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.
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Using the OECD statistical calculation procedure the recommended tolerance for onion bulb is 

0.7 ppm.

Table I-1. Residue data used to calculate tolerances for zoxamide on onion bulb.

Regulator: EPA

Chemical: Zoxamide

Crop: Onion bulb

PHI: 6-8 days

App. Rate: 1.32-1.34 lb ai/A

Submitter: Gowan

MRID Citation: MRID 49067102

Combined residues 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 spreadsheet summary of zoxamide 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) 0.113
Zoxamide Summary of Analytical Chemistry and Residue Data DP#: 416653

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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