Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D429732

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

MEMORANDUM

Date: 10-February-2016

Subject: CLOFENTEZINE: Revised Petition for the Establishment of Permanent Tolerances 

and Registration for New Use on Avocado and Papaya and Crop Group/Subgroup 

Expansions for Pome Fruit, Group 11-10; Cherry Subgroup 12-12A; Peach Subgroup 

12-12B and Fruit, small, vine climbing, except fuzzy kiwifruit, Subgroup 13-07F, 

Summary of Analytical Chemistry and Residue Data.

PC Code: 125501 DP Barcode No.: D429732

Decision No.: 495217 Registration Nos.: 74054-1, 66222-47

Petition No.: 4E8312 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case No.: 7602

TXR No.: NA CAS No.: 74115-24-5

MRID No.: 49446901 40 CFR §180.446

From: P. Yvonne Barnes, Chemist

Risk Assessment Branch VI

Health Effects Division (HED; 7509P)

Through: Michael A. Doherty, Ph.D., Senior Chemist

Meheret Negussie, Chemist

Chemistry Science Advisory Council

and

Donna S. Davis, Acting Chief

Risk Assessment Branch VI

HED (7509P)

To: Evisabel Craig, Toxicologist and Risk Assessor

Risk Assessment Branch VI

HED (7509P)

 and

Andrew Ertman/Barbara Madden, RM 05

Risk Integration, Minor Use, Emergency Response Branch

Registration Division (RD; 7505P)
Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D429732

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OCSPP 860 

Series Guideline

MRID 

Number Title

1500 49446901

Barney, W. (2014) Clofentezine: Magnitude of the Residue on Avocado. Study 

No. 09321. Laboratory Identification Number: 09321.12 - CAR04. Unpublished 

study prepared by IR-4. 118 p
Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D429732

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Table of Contents

1.0 Executive Summary................................................................................................................ 4

2.0 Regulatory Recommendations................................................................................................ 5

2.1 Deficiencies/Data Needs.................................................................................................. 5

2.2 Tolerance Considerations................................................................................................. 5

2.2.1 Enforcement Analytical Method............................................................................... 5

2.2.2 Recommended Tolerances........................................................................................ 5

2.2.3 Revisions to Petitioned For Tolerances .................................................................... 6

2.2.4 International Harmonization ..................................................................................... 6

2.3 Label Recommendations.................................................................................................. 6

3.0 Introduction............................................................................................................................. 7

3.1 Chemical Identity ............................................................................................................. 7

3.2 Physical/Chemical Characteristics................................................................................... 7

3.3 Pesticide Use Pattern/Directions for Use (860.1200)....................................................... 8

4.0 Metabolite/Degradate Residue Profile.................................................................................... 9

4.1 Nature of the Residue....................................................................................................... 9

5.0 Residue Profile........................................................................................................................ 9

5.1 Residue Analytical Methods (860.1340).......................................................................... 9

5.1.1 Multi-Residue Methods (860.1360)........................................................................ 10

5.1.2 Tolerance Enforcement Methods............................................................................ 10

5.1.3 Submittal of Analytical Reference Standards (860.1650) ...................................... 10

5.2 Storage Stability (860.1380) .......................................................................................... 10

5.3 Residue Data .................................................................................................................. 11

5.3.4 Processed Food and Feed (860.1520)..................................................................... 12

5.3.5 Meat, Milk, Poultry and Eggs (860.1480) .............................................................. 13

5.3.6 Food Handling (860.1460)...................................................................................... 13

5.3.7 Water, Fish, and Irrigated Crops (860.1400).......................................................... 13

6.0 Tolerance Derivation ............................................................................................................ 13

Appendix B. Field Trial Geographic Distribution for Avocado .................................................. 15

Appendix C. Stability of Clofentezine Residues in Avocado...................................................... 16

Appendix D. OECD MRL Calculator Results for Clofentezine in/on the Avocado ................... 17
Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D429732

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1.0 Executive Summary

Clofentezine (3,6-bis (2-chlorophenyl)-1,2,4,5-tetrazine) is an acaricide that is currently 

registered as a suspension concentrate formulation for use on almonds, apples, apricots, cherries, 

Christmas trees, grapes, nectarines, ornamentals (greenhouse and outdoor), peaches, pears, 

persimmons, and walnuts.

Interregional Research Project, Number 4 (IR-4) in cooperation with Makhteshim Agan of 

North America, Inc., has submitted a Section 3 registration request for a new use in/on avocado 

and papaya. Furthermore, IR-4 has proposed expanding the existing tolerances to cover 

additional commodities that are included in the revised crop group/subgroups 11-10, 12-12A, 12-

12B, and 13-07F. 

IR-4 has submitted field trial data for clofentezine on avocado. Five field trials were 

conducted in the United States during the 2012 growing season in a manner matching the 

proposed use pattern for avocado and papaya. The treated plot received a single foliar directed 

application of a 4 lbs a.i/gal suspension concentrate (SC) formulation of clofentezine at 0.251-

0.256 lb a.i/A, and avocados were harvested 2-4 days after the application. The residue trials are 

supported by adequate analytical method and storage stability data. Quantifiable residues were 

found in/on the avocado raw agricultural commodities (RACs), and recommended tolerance 

level of 0.30 ppm was obtained using the Organization for Economic Cooperation and 

Development (OECD) calculation spreadsheet procedures. HED will extrapolate the avocado 

clofentezine tolerance to papaya (Chemistry Science Advisory Council, (ChemSAC,

07/30/2014). The number and geographic representation of the field trials are adequate. 

No new data was submitted to support the proposed crop group/subgroup expansions. 

Available data on representative commodities for each crop group or crop subgroup, including 

processing studies, are adequate to support the petitioned expansions.

There are no animal feed crops associated with the proposed new uses on avocado and 

papaya, nor any new animal feedstuffs associated with the expansion of uses to crop 

groups/subgroups; consequently, the established tolerances for residues in livestock commodities 

are adequate. Therefore a discussion of the livestock metabolism is not required to address these 

petitions.

The metabolic fate of clofentezine residues in plants (fruit crops only) is adequately 

understood. In fruit crops, the residue of concern (ROC) is the parent, clofentezine, for tolerance 

enforcement and risk assessment purposes. 

There is an adequate analytical enforcement method available to enforce the proposed 

tolerances. Multiresidue methods in FDA’s analytical method (PAM-I) were found to be 

inadequate for tolerance enforcement due to poor recoveries. 

Analytical reference standards for clofentezine (expires 10/25/2015) are currently 

available at the EPA National Pesticide Standards Repository. 

The US grape tolerance covering the expanded fruit, small, vine climbing, except fuzzy 

kiwifruit, subgroup 13-07F established at 1.0 ppm if changed would create export issues with 
Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D429732

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Japan and Korea that maintain a grape MRL at 1.0 ppm. The US grape tolerance will remain at 

1.0. However, maintaining the US grape tolerance at 1.0 ppm does not harmonize with the 

Codex MRL of 2.0 ppm.

2.0 Regulatory Recommendations

HED has examined the residue chemistry database for clofentezine. There are no residue 

chemistry data deficiencies that would preclude the establishment of permanent tolerances for 

residues of clofentezine in/on avocado, papaya and the proposed crop subgroup/group 

expansions as outlined in Table 2.2.2.

A human-health risk assessment will be prepared as a separate document. 

2.1 Deficiencies/Data Needs

No residue chemistry data deficiencies have been noted relative to these petitioned actions. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An HPLC analytical method for the determination of clofentezine residues in/on apples 

was submitted with PP# 3F3392 (MRID# 44202401). Briefly, fruit samples are extracted into 

acetone and filtered. An aliquot of the extract is removed and partitioned with hexane. The 

organic extract is rotary evaporated to dryness then reconstituted in hexane for clean up through 

a silica solid phase extraction cartridge. The clofentezine is eluted from the silica, evaporated to 

dryness, adjusted to the final volume and quantified using high performance liquid 

chromatography with UV detection at 268 nm. This method originally could detect 0.01 ppm 

clofentezine in apples but only 0.05 ppm in apple pomace. The method was modified to enhance 

its limit of quantitation for apple pomace and had recoveries of 64 to 100% from fortifications of 

0.01 ppm in apples and 69 to 83% from fortifications of 0.01 ppm in apple pomace.

Control samples showed no detectable residues. Method trials were conducted on apples 

at 0.5 and 1 ppm and on apple pomace at 10 ppm. The limit of quantitation (LOQ) and limit of 

detection (LOD) were determined to be 0.01 ppm and 0.003 ppm, respectively. A petition 

method validation (PMV) was successfully completed by the EPA Analytical Chemistry 

Laboratory, and the method was found acceptable. HED concludes that the method is suitable 

for enforcement purposes. The limit of quantitation (LOQ) and limit of detection (LOD) were 

determined to be 0.01 ppm and 0.003 ppm, respectively. A petition method validation (PMV)

was successfully completed by the EPA Analytical Chemistry Laboratory, and the method was 

found acceptable. HED concludes that the method is suitable for enforcement purposes.

2.2.2 Recommended Tolerances

The tolerance expressions established under 40 CFR §180.446 comply with the HED 

Interim Guidance on Tolerance Expressions (S. Knizner, 05/27/2009); no revisions are 

necessary. A tolerance summary is presented in Table 2.2.2 below.
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Table 2.2.2 Tolerance Summary for Clofentezine

Commodity

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance 

(ppm)

Correct Commodity Definition/Comments

To be established under 40 CFR §180.446 (a) General. (1)

Cherry, subgroup 12-12A 1.0 1.0 Established tolerance for cherry (1.0 ppm) 

should be removed from the 40CFR and 

replaced by this subgroup tolerance.

Fruit, pome, group 11-10 0.5 0.50 Established tolerance for apple and pear (0.5 

ppm) should be removed from 40CFR and 

replaced by this group tolerance.

Peach, subgroup 12-12B 1.0 1.0 Established tolerance for peach should be 

removed from the 40CFR and replaced by this 

group tolerance.

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

Subgroup 13-07F 

1.0 1.0 Established tolerance for grape (1 ppm) should 

be removed from the 40CFR and replaced by 

this subgroup tolerance.

Avocado 0.3 0.30

Papaya 0.3 0.30

2.2.3 Revisions to Petitioned For Tolerances

None.

2.2.4 International Harmonization

The International Residue Limit (IRL) Status Sheet is attached in Appendix A. The 

recommended tolerance for residues of clofentizine in/on avocado and papaya is 0.30 ppm based 

on the parent only. There are no Codex/Canadian MRLs on avocado and papaya. There are no 

US, Codex or Canadian harmonization issues for fruit, pome, group 11-10. There are no US and 

Canadian harmonization issues for peach, subgroup 12-12B. The US tolerance and Codex MRL 

are not harmonized on cherry, subgroup 12-12A and peach subgroup 12-12B. The Codex MRL 

was established at 0.5 ppm on stone fruits. The clofentezine residues in/on representative crops 

cherry and peach are greater than 0.5 ppm and would result a tolerance exceedance for US 

growers. 

The US grape tolerance and its expansion to fruit, small, vine climbing, except fuzzy 

kiwifruit, subgroup 13-07F at 1.0 ppm does not harmonize with the Codex MRL of 2.0 ppm. The 

petitioner proposes to maintain the US grape tolerance at 1.0 ppm because several countries 

including Japan and Korea also maintain an MRL at 1.0 ppm and it would create export issues if

the US grape tolerance were to change. 

2.3 Label Recommendations

The proposed labels are adequate and supported by data. No revision to the labels is required. 
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3.0 Introduction

Clofentezine (3,6-bis (2-chlorophenyl)-1,2,4,5-tetrazine) is an acaricide that is used in 

plant protection products for the control of spider mites. It acts primarily as an ovicide, but it has 

some activity against early motile stages of mites. Clofentezine is currently registered for use on 

almonds, apples, apricots, cherries, Christmas trees, grapes, nectarines, ornamentals (greenhouse 

and outdoor), peaches, pears, persimmons, and walnuts.

3.1 Chemical Identity

The chemical structure and nomenclature of clofentezine are shown in Table 3.1, and the 

physicochemical properties of the technical grade of clofentezine are given in Table 3.2.

Table 3.1 Clofentezine Nomenclature

Chemical Structure

Common Name Clofentezine

IUPAC name 3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine

CAS Name 3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine

CAS Registry Number 74115-24-5

3.2 Physical/Chemical Characteristics

Clofentezine’s vapor pressure (9.75 x 10-10 mm Hg @ 25 °C) and Henry's Law Constant 

0.168 Pa×m3/mol indicate that the compound is non-volatile under field conditions. Clofentezine 

has a low solubility (34.2 mg/L) in water; however, clofentezine is fairly persistent in the 

environment. Based on the use pattern and environmental fate parameters, there is the potential 

for clofentezine to reach water resources. The octanol/water partition coefficient for clofentezine 

indicates that it may have the potential to accumulate into fatty tissues.

The physical/chemical properties of this active ingredient are summarized in the Table 

3.2 below.

Table 3.2 Clofentezine Physical and Chemical Properties

Parameter Value

Molecular Weight 303.1 g/mol

Water solubility (20 °C) 2.9 x 10-2 mg/L

Vapor pressure (25 °C) 9.75 x 10-10 mm Hg

Henry’s Law Constant (25 °C) 0.168 Pa×m3/mol 

Octanol/water partition coefficient (25 °C) log Kow = 3.1
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3.3 Pesticide Use Pattern/Directions for Use (860.1200)

Clofentezine is formulated as a suspension concentrate containing 42% active ingredient 

or 1.0 lb active ingredient per quart (i.e., 4.0 lbs a.i/gallon). Two end-use products are 

registered: Apollo® SC Ovicide/Miticide (EPA Reg. No. 66222-47) and Clofentezine SC (EPA 

Reg. No. 66222-53). Clofentezine is applied at the first sign of mites by ground equipment 

through airblast, groundboom machinery, and handheld equipment once per year. It may not be 

applied aerially or through any type of irrigation system. There are no registered residential uses 

for clofentezine. 

The Section 3 registration requested by IR-4, in cooperation with the registrant, 

Makhteshim Agan of North America, Inc. proposes the use of Apollo® SC Ovicide/Miticide on 

avocado, papaya, as well as the following crop subgroups: cherry subgroup (12-12A), peach

subgroup (12-12B), pome fruit group (11-10), and small fruit vine climbing except fuzzy 

subgroup (13-07F). The new uses and crop group/subgroups have the same maximum rate (0.25 

lb a.i/A on orchard type crops) and the same pre-harvest interval (PHI) as the previously 

registered crops. The PHI for avocado and papaya is 3 days. The PHI for the pome fruit group

is 45 days. The PHI for the cherries, small fruit, vine climbing except fuzzy kiwi and peaches is 

21 days and (10 days for peaches in California). The proposed uses and application rates are 

further described in Table 3.3.

Table 3.3. Summary of Directions for Proposed Use for Clofentezine 

APOLLO® Suspension Concentrate (SC) - EPA Reg. No. 66222-47 - 4 lbs. a.i/gal

Application. 

Equipment Crop Maximum Application Rate PHI (days) Use Directions and Limitations

Airblast, 

Groundboom, 

and Handheld 

Equipment

Avocado

8 oz. product/A

0.25 lb a.i/A

3 Do not apply via aerial or 

chemigation. Do not make more 

than one applications of product 

per year. PPE includes baseline 

attire (a long-sleeved shirt and 

long pants, and shoes plus socks) 

and gloves. Do not graze livestock 

in treated areas or harvest the

cover crop for livestock feed.

Papaya

Fruit, pome, group 11-10 45 

Pears and Asian pear

21 

and

(10 days 

Peaches 

California)

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

Cherry, subgroup 12-12A

Peach, subgroup 12-12B

Conclusions: The petitioner has requested that existing uses be expanded to pome fruit group 11-

10, cherry subgroup 12-12A, peach subgroup 12-12B, and fruit, small, vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F. The existing directions for use for these crops are unchanged 

other than the additional crops covered by the updated groups/subgroups. The use directions 

applicable to the avocado is translated to the papaya. The labels are adequate to evaluate the 

residue chemistry data relative to the petitioned crop subgroups/groups actions.
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4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue

DP Barcode D247526 and D251946, Jennifer Rowell, 04/02/1999

No new metabolism data was submitted or required to support this petition.

The nature of the residue has been adequately delineated in fruit crops for Clofentezine. 

In fruit crops, the residue of concern is the parent, Clofentezine (A. Smith, 04/26/1988; RCB 

Nos. 3190 and 3191). Table 4.4 provides a summary.

Table 4.4 Summary of Metabolites and Degradates to be included in the Risk Assessment and 

Tolerance Expression

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Primary Crop Clofentezine Clofentezine

Drinking Water Clofentezine Not Applicable

1 Livestock residues of concern are not considered in this action.

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340) 

49446901. der

Samples were analyzed for residues of Clofentezine using high performance liquid 

chromatography with tandem mass spectrometry detection (LC/MS/MS).

Briefly, samples were extracted twice with acetonitrile (ACN), then centrifuged and 

filtered. The extracts were combined and reduced by rotary evaporation. Following the addition 

of acetone, the extract was purified by sequential solid phase extraction on Strata-X, amino 

(NH2), and CUCARB cartridges. Residues were eluted through the Strata-X and amino 

cartridges with acetone, and were eluted from the CUCARB cartridge with 20% benzene in 

dichloromethane. The eluate was evaporated to dryness and re-dissolved in acetone: ACN 

(50:50, v: v) for LC/MS/MS analysis.

The LOQ (determined as the lowest level of method validation, LLMV) was 0.02 ppm 

for clofentezine, and the experimental LOD was 0.003 ppm. We note that the petitioner also 

presented calculated values for the LOD and LOQ based on the recoveries obtained at the 0.02-

ppm fortification levels. The LOD was calculated by multiplying the standard deviation of 

recovery measurements at the LLMV by the one-tailed t-statistic (confidence level not reported) 

for six replicates, and the LOQ was defined as 3X the LOD. The calculated LOD was 0.003

ppm, and the calculated LOQ was 0.01ppm.
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Method performance was evaluated during method validation and by use of concurrent 

recovery samples. For method validation and concurrent recovery, samples of untreated avocado 

were fortified with clofentezine at 0.02, 0.1, and 1 ppm. Recoveries were within the range of 70-

120 %. The fortification levels bracketed the measured residues. Concurrent recoveries were 

not corrected for apparent residues in controls. 

Conclusions: The analytical method used for the residue trials was adequately validated for 

purposes of data collection. 

5.1.1 Multi-Residue Methods (860.1360)

DP Barcode D247526 and D251946, Jennifer Rowell, 04/02/1999

Multiresidue methods in FDA’s analytical method (PAM-I) were found to be unacceptable for tolerance enforcement (due to poor recoveries). 

5.1.2 Tolerance Enforcement Methods

See Section 2.2.1.

5.1.3 Submittal of Analytical Reference Standards (860.1650)

Analytical standards of clofentezine and its regulated metabolite are available (expires 

10/25/2015) at the National Pesticide Standards Repository. As reminder to the petitioner, 

supplies of analytical standards must be replenished as requested by the repository as long as the 

tolerance is published in 40 CFR180.446. The address is as follows:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note: all mail will be returned if the extended zip code is not used.)

5.2 Storage Stability (860.1380)

49446901. der

The submitted storage stability study indicated that samples of avocado were stored 

frozen for a maximum of 205 days (~ 6.7 months) from harvest to extraction. Samples were 

extracted and analyzed on the same day. To support sample storage durations, a concurrent 

storage stability study was conducted along with the field trial study. The 229-day interval was 

the only data point provided. No 0-day data were provided, such that the initial concentration is 

unknown at (e.g., time zero) 0-day. Storage stability studies should always include a 0-day 

sampling interval to establish the residue levels present at the time samples are placed into 

storage [see OCSPP 860.1380(d)(6)(i)]. However acceptable storage stabilty data are available 

for the storage duration for the avocado. These data demonstrate that residues of clofentezine 

were stable to cover avocado stored frozen for up to 229 days (~ 7.5 months).
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Available storage stability data have shown that clofentezine residues are stable in apples 

for up to 381 days (Memo, M. J. Bradley, August 17, 1994; PP#:6F3392/6H5500), in peaches for 

up to 2 years (Memo, R. Griffin, 05/22/1990; PP#:9F3699) and in almonds for one year

(Memo, M. Bradley, 08/15/1990; PP#:9F3793). Based on these data, HED concluded that

residues of clofentezine are stable in grapes and persimmons for up to one year of frozen storage.

A previously reviewed evaluation of analytical methods and residue data of clofentezine 

for petition PP# 9F3793 (M. J. Bradley, March 07, 1990) determined that clofentezine was 

essentially stable in almond hulls for over two years, and fairly stable in almond nutmeat for one 

year. An evaluation of analytical methods and residue data of clofentezine in/on peaches for 

petition PP# 9F3699 (F. Toghrol, April 21, 1989) determined that no significant degradation of 

clofentezine occurs in peaches when stored at ~15 °C for up to two years.

Conclusions: Previously submitted storage stability data (i.e., apples, almonds, grapes, peaches 

and persimmons) support the storage conditions and durations of the stored samples in the 

avocado magnitude of the residue studies which is translated to papaya. These storage stability 

data are adequate to show that residues of clofentizine remain stable during frozen storage 

periods associated with the avocado residue trials. 

5.3 Residue Data

49446901.der

Avocado

Five field trials were conducted in the United States during the 2012 growing season in 

the North American Free Trade Agreement (NAFTA) Growing Zones 3 (FL; 1 trial) and 10 (CA; 

4 trials). Each trial consisted of one untreated plot and one treated plot. At each crop trial 

location, the treated plot received a single, foliar-directed application of a 4 lbs a.i/gal suspension 

concentrate (SC) formulation (Apollo SC) of clofentezine at 0.251-0.256 lb a.i/A. The crop field 

trials from California have been assessed for independence. Although the CA crop field trial 

locations were less than 20 miles apart and of the same variety the initial application of the 

pesticide was off-set by at least 30 days. HED concludes that these field trials are considered 

separate based on the timing of the pesticide application.

Applications were made using ground equipment in spray volumes of 60-230 gals/A 

during the fruiting stage of development samples of avocados were harvested at a PHI of 2-4 

days after the application; additional samples from one trial (CA21) were collected at 0, 7, 9, and 

14-day PHIs to assess residue decline. In avocados harvested 2-4 days following application,

residues (and per-trial averages) were 0.0376-0.127 ppm (0.0439-0.106 ppm).

Acceptable method validation and concurrent recoveries were reported for samples 

fortified with clofentezine at 0.02-1 ppm, thus validating the method. The residue of concern for 

plants is clofentezine (parent only). The LOQ (determined as the LLMV) was 0.02 ppm. 

A summary of residue data for clofentezine in/on avocado is presented in Table 5.3.

 
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Table 5.3 Summary of Residues from Avocado Field Trials with Clofentezine.

Crop 

Matrix

Analyte Total 

Application 

Rate

(lb a.i/A)

PHI 

(days) n

1

Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median Mean SD3

Avocado Clofentezine 0.251-0.256 2-4 5 0.0376 0.127 0.0439 0.106 0.0874 0.0847 0.0292

1 n = number of field trials.

2 Values based on total number of samples.

3 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard deviation.

Papaya

IR-4 petitioned to translate the available data from avocado to papaya. Avocado is being 

proposed as a representative crop for the new Crop Subgroup 24B, Tropical and Subtropical, 

Medium to Large Fruit, Smooth, and Inedible Peel. This proposal was brought to the ChemSAC. 

The ChemSAC determined that the translation of avocado data to papaya was appropriate,

provided the number of field trials and geographical locations was adequate (ChemSAC 

07/30/2014).

Crop Group/Subgroup Expansions

No new crop field trial data were submitted nor are any required because the existing 

residue data are adequate to support the petitioned actions. All crops included in the crop group/

subgroup expansions will be treated at the same rate and timing as the currently registered crops. 

The proposed crop group/subgroups expansions are listed as follows: pome fruit, group 11-10;

cherry subgroup 12-12A; peach subgroup 12-12B and fruit, small, vine climbing, except fuzzy 

kiwifruit, subgroup 13-07F. 

Conclusions: The submitted avocado residue data are adequate in terms of both number and 

geographic representation to support the new use on the avocado. The residue decline data 

indicated that residues of clofentezine decreased with increasing PHI in/on avocados. The 

avocado residue data support a tolerance of 0.30 ppm for residues of clofentezine in/on avocado. 

Therefore, HED is recommending for a tolerance for residues of clofentezine in papaya at 0.30 

ppm.

No new field trial data are required to support the requested tolerance group/subgroup 

expansions.

5.3.4 Processed Food and Feed (860.1520)

DP Barcode D247526 and D251946, Jennifer Rowell, 04/02/1999

Memo of H. Fonouni, PP9F3705/9H5572, 12/15/1988

Processing studies for the currently registered clofentezine uses are adequate. 

Clofentezine processing studies are available for apples and grapes. The apple juice processing 

factor was also translated to pear juice. 

Conclusion: Processing studies for the currently registered clofentezine uses are adequate. No 

processing food or feed is associated with the requested new uses (avocado and papaya),

moreover, there are no processing studies required for papaya (dried, juice), cherry, apple

(dried), pear (dried) or peach (dried). Associated with the expanded crop group/subgroups are 

processing study requirements for grape (juice, raison) and apple (juice).
Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D429732

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5.3.5 Meat, Milk, Poultry and Eggs (860.1480)

DP Barcode D247526 and D251946, Jennifer Rowell, 04/02/1999

There are no animal feed items associated with the new uses on avocado and papaya or 

with any new commodities as a result of crop group updating. 

Conclusions: The currently established tolerances for residues of clofentezine in livestock 

commodities are thus adequate to support this petition,

5.3.6 Food Handling (860.1460)

There are no petitioned uses that are relevant to this guideline topic.

 

5.3.7 Water, Fish, and Irrigated Crops (860.1400)

There are no petitioned uses that are related to this guideline topic.

6.0 Tolerance Derivation

HED used the Organization for Economic Cooperation and Development (OECD) MRL 

calculation procedures to determine appropriate tolerance levels for the residues of clofentizine.

The results from the spreadsheet calculator support the proposed tolerances. The inputs and the 

outputs from the calculator are shown in Appendix C. The data support a tolerance of 0.30 ppm 

for residues of clofentezine in/on avocado and papaya.

HED concurs with the petitioner’s request to convert representative commodity tolerances

to their respective crop groups or subgroup per the petitioned request. HED's tolerance 

recommendations are summarized in Table 2.2.2.
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Appendix A. International Residue Limits Table

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

40 CFR 180.446: Clofentezine

Plant: Clofentezine

Livestock: Clofentezine and 3-(2-chloro-4-

hydroxyphenyl)-6-(2-chlorophenyl)-1,2,4,5-

tetrazine metabolite

Plant: Clofentezine

Livestock and dairy: 3,6-

bis(2-chlorophenyl)-

1,2,4,5-tetrazine, 

including the metabolite 

3-(2-chloro-4-

hydroxyphenyl)-6-(2-

chlorophenyl)-1,2,4,5-

tetrazine

Plant commodities: 

clofentezine 

Animal commodities:

sum of clofentezine, 

and all metabolites 

containing the 2-

chlorobenzoyl 

moiety, expressed as 

clofentezine 

The residue is fat 

soluble.

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

US Canada Mexico2 Codex

Avocado 0.3

Papaya 0.3

Fruit pome group 11-10 0.5 0.5 apple, pear 0.5 

Cherry, subgroup 12-12A 1.0 0.5 stone fruits

Peach, subgroup 12-12B 1.0 1.0 nectarine, peach

Fruit, small, vine climbing, except 

fuzzy kiwifruit, Subgroup 13-07F 1.0

2.0 grapes, 

dried grapes = 

(currants, raisins and 

sultanas)

Completed by: M. Negussie, 05/11/2015

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.
Clofentezine Summary of Analytical Chemistry and Residue Data Barcode: D423333

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Appendix B. Field Trial Geographic Distribution for Avocado

Trial Numbers and Geographical Locations

NAFTA Growing Zones

Total Number Crop Number of Trials 3 10

Avocado

Submitted 1 4 5

Required 1 1 4 5

 1 As per Table 5 of OCSPP guideline 860.1500 for avocado.
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Appendix C. Stability of Clofentezine Residues in Avocado

Stability of Clofentezine Residues in Avocado.

Commodity Spike 

Level

(ppm)

Storage interval

(days)

Fresh Fortification 

Recoveries (%)

[Avg.]

Stored Sample 

Recoveries (%)

Mean 

Recovery (%)

Corrected % 

recovery1

Avocado 0.1 229 79, 84, 87

[83]

52, 58, 51 54 64
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Appendix D. OECD MRL Calculator Results for Clofentezine in/on the Avocado

Tolerance values were calculated by the OECD MRL Calculator using data from the avocado 

field trial residue study (MRID 49446901) for a 0.25 lb a.i/A clofentezine use rate and a 3-day 

PHI for the Avocado:

CLOFENTEZINE

AVOCADO

Country U.S.A

3 days PHI/0.25 lb a.i.

Total number of data (n) 5

Percentage of censored data 0%

Number of non-censored data 5

Lowest residue 0.044

Highest residue 0.110

Median residue 0.100

Mean 0.087

Standard deviation (SD) 0.029

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.110

- Mean + 4 SD 0.203

- CF x 3 Mean 0.260

Unrounded MRL 0.260

Rounded MRL 0.3

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg) n

0.044 1

0.069 1

0.1 1

0.11 2