Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

MEMORANDUM

Date: April 29, 2015

Subject: Oxathiapiprolin. Petition for the Establishment of Permanent Tolerances and 

Registration for Use of the New Active Ingredient on a Number of Crops. Summary

of Analytical Chemistry and Residue Data.

PC Code: 128111 DP Barcode: D426128

Decision No.: 485920 Registration Nos.: 352-IOR, 352-IOE, 

 100-RLGE, 100-RLGG

Petition No.: 3F8220 Regulatory Action: Section 3

Risk Assessment Type: NA Case No.: None

TXR No.: NA CAS No.: 1003318-67-9

MRID No.: See Appendix K 40 CFR: New Active Ingredient

From: Elizabeth Holman, Physical Scientist

Risk Assessment Branch II

Health Effects Division (HED; 7509P)

Through: Douglas A. Dotson, Ph.D., Senior Chemist

Risk Assessment Branch II; HED (7509P)

Danette Drew, ChemSAC Designated Reviewer (HED; 7509P)

Donna S. Davis, ChemSAC Chair (HED; 7509)

Julie L. Van Alstine, M.P.H., ChemSAC Chair (HED; 7509)

To: Marcel Howard/Tony Kish

Fungicide Branch

Registration Division (7505P)
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

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Table of Contents

1.0 Executive Summary..................................................................................................................3

2.0 Regulatory Recommendations..................................................................................................4

2.1 Data Deficiencies/Data Needs...........................................................................................4

2.2 Tolerance Considerations..................................................................................................4

2.2.1 Enforcement Analytical Method............................................................................4

2.2.2 Recommended Tolerances.....................................................................................6

2.2.3 Revisions to Petitioned-For Tolerances.................................................................7

2.2.4 International Harmonization..................................................................................8

3.0 Introduction...............................................................................................................................8

3.1 Chemical Identity ..............................................................................................................9

3.2 Physical/Chemical Characteristics ....................................................................................9

3.3 Pesticide Use Pattern/Directions for Use (860.1200)......................................................10

4.0 Metabolite/Degradate Residue Profile....................................................................................11

4.1 Nature of the Residue ......................................................................................................11

4.1.1 Summary of Plant Metabolism (860.1300)..........................................................14

4.1.2 Summary of Livestock Metabolism (860.1300)..................................................18

4.1.3 Summary of Confined Rotational Crops (860.l850)............................................22

4.1.4 Summary of Metabolites and Degradates............................................................24

4.2 Comparison of Metabolic Pathways................................................................................24

4.3 Residues of Concern Summary and Rationale ................................................................24

5.0 Residue Profile........................................................................................................................26

5.1 Residue Analytical Methods (860.1340).........................................................................26

5.1.1 Data Collection Methods.....................................................................................26

5.1.2 Multi-Residue Methods (860.1360).....................................................................28

5.1.3 Tolerance Enforcement Methods.........................................................................29

5.1.4 Submittal of Analytical Reference Standards (860.1650) ...................................30

5.2 Storage Stability (860.1380)............................................................................................30

5.3 Residue Data....................................................................................................................31

5.3.1 Crop Field Trials (860.1500) ...............................................................................31

5.3.2 Field Rotational Crops (860.1900) ......................................................................40

5.3.3 Processed Food and Feed (860.1520)..................................................................42

5.3.4 Meat, Milk, Poultry and Eggs (860.1480) ...........................................................45

5.3.5. Food Handling (860.1460)..................................................................................46

5.3.6 Water, Fish, and Irrigated Crops (860.1400).......................................................46

5.4 Food Residue Profile .......................................................................................................47

6.0 Tolerance Derivation ..............................................................................................................47

7.0 ChemSAC Reference..............................................................................................................49
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1.0 Executive Summary

Oxathiapiprolin {1-[4-[4-[5-(2,6-Difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-

piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone} is a piperidinyl 

thiazole isoxazoline fungicide for control of crop diseases caused by oomycetes (downy mildew 

and late blight). Syngenta is proposing this chemical for use on turf and ornamentals, whereas 

Dupont Chemical Company is proposing uses on a number of crops. With the exception of 

grapes, all crops are proposed for Section 3 use in the U.S. Grapes are being proposed for a 

tolerance without a US registration (import tolerance) based on a proposed use in the European 

Union (EU). The proposed agricultural crop uses include ginseng, tuberous and corm 

vegetables, bulb vegetables, fruiting vegetables, leafy greens, head and stem Brassica vegetables, 

succulent peas, cucurbits, and tobacco. For tomatoes, peppers, and edible-peel cucurbits, both 

field and greenhouse uses are proposed, with the use pattern being identical for these uses. 

HED is performing this assessment as a joint review with global partners PMRA/Canada and 

APVMA/Australia, with Japan and China/ICAMA acting as observers. 

Two agricultural products, formulated as an oil dispersion (OD) or suspension concentrate (SC),

are proposed for use on these various crops. The OD formulation contains 10.2% of the active 

ingredient (0.83 lb ai/gal), whereas the SC formulation contains 18.7% of the active ingredient 

(1.67 lb ai/gal). 

Oxathiapiprolin is generally applied 2-4 times per growing season with a minimum 3- to 14-day

retreatment interval depending on crop, pest, and country/region. The single application rates for 

the U.S. use pattern range from 35 to 280 g ai /ha (0.03-0.25 lb ai/A) for crop uses. The 

maximum seasonal application rate is 560 g ai/ha (0.50 lb ai/A) for crop uses. Preharvest 

intervals (PHI) range from 0 to 14 days. 

The residue chemistry database includes submissions addressing analytical methods; metabolism 

in target crops, rotational crops, and livestock; storage stability; residues from field trials; and 

residues in processed commodities. Based on the requested uses, feeding studies and tolerances 

in livestock are not required at this time and the database is considered to be complete. In 

rotational crops, HED is recommending establishing tolerances for inadvertent residues at 0.10 

ppm for the purposes of harmonization with global partners. 

The proposed analytical enforcement method for crop commodities includes instructions for 

quantification of parent and seven metabolites. The seven metabolites are IN-E8S72, INWR791, IN-RDG40, IN-Q7H09, IN-SXS67, IN-RZB20 and IN-RZD74. Analytical methods 

suitable for enforcement and data gathering have been developed and validated. The limit of 

quantitation (LOQ) is 0.01 ppm for parent and all seven metabolites. 

Crop field trials with oxathiapiprolin were conducted according to Good Agricultural Practice 

(GAP) in the U.S. and Canada with potato, tomato, pepper (bell and non-bell), cucumber, 

summer squash, cantaloupe, tobacco, ginseng, succulent pea, lettuce, spinach, Brassica

vegetables, and bulb and green onion. In addition, adequate EU field trial data on grape have 

been submitted to support the proposed tolerance without a US registration. With the exception 

of the potato field trials where no quantifiable oxathiapiprolin residues were observed, one or 
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more field trials from all other primary crops had quantifiable oxathiapiprolin residues. These 

oxathiapiprolin residues were generally substantially higher than residues of any of the seven 

metabolites listed above. Consequently, the residue of concern in plant commodities (treated as 

primary crops) is solely parent oxathiapiprolin. Based on the submitted decline trial data, 

residues of oxathiapiprolin generally decline with increasing PHI. All residue study results are 

supported by adequate storage stability data, and these field trial studies were conducted using an 

adequately validated analytical enforcement method. 

The registrant also submitted potato, tomato, and grape processing studies which were conducted 

at exaggerated use rates. Based on a review of these processing studies, separate tolerances are 

not required for processed potato or grape commodities. Based on the tomato processing study

results, oxathiapiprolin is not expected to concentrate in tomato juice, paste, or puree – the 

commodities for which HED typically makes tolerance recommendations. However, 

oxathiapiprolin concentrates in sundried tomato, with a median processing factor of 6.9X. Based 

on the tomato HAFT oxathiapiprolin residue of 0.31 ppm, the anticipated residue of 

oxathiapiprolin is 2.1 ppm in dried tomato (0.31 ppm x median PF (6.9) = 2.1 ppm). Although 

HED would not normally set tolerances in dried tomato, the registrant has petitioned for a dried 

fruiting vegetable tolerance. For simplicity purposes in tolerance setting, the anticipated residue 

in dried tomato of 2.1 ppm is rounded up to the HED-recommended value of 3.0 ppm. Although 

HED would not normally set such a tolerance, HED concludes that setting a tolerance value of 

3.0 ppm for dried tomato would be appropriate (ChemSAC minutes 04/01/2015). However, 

HED has concluded that setting a crop group tolerance for all dried fruiting vegetables is not 

appropriate, as our regulations do not currently permit setting a crop group processed commodity

tolerance (ChemSAC minutes 04/01/2015). 

 

2.0 Regulatory Recommendations

There are no residue chemistry considerations that would preclude granting the requested 

registration and establishing the recommended tolerances for oxathiapiprolin residues on the 

proposed crops. The specific tolerance recommendations are discussed in Section 2.2.

2.1 Data Deficiencies/Data Needs

There are no residue chemistry data deficiencies at this time. The HED notes that livestock 

feeding studies will likely be necessary to support any future use requests that involve crops 

which are significant livestock feeds. 

2.2 Tolerance Considerations

Due to the lack of toxicity from oxathiapiprolin, USEPA would normally grant a tolerance 

exemption for this chemical. However, given that this chemical is being assessed as part of a 

global joint review and is intended to be registered in other countries, the Agency is setting 

tolerances for the purposes of harmonization. 

2.2.1 Enforcement Analytical Method

MRID No. 49011136 (Plants)
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MRID No. 49011145 (Livestock)

Suitable methods for tolerance enforcement have been developed and independently validated. 

For all matrices and analytes, the LOQ, defined as the lowest level of method validation (LLMV) 

or lowest spiking level where acceptable precision and accuracy data were obtained, was 

determined to be 0.01 ppm. The limit of detection (LOD) was defined to be 30% of the LOQ 

(i.e., 0.003 ppm). The FDA multi-residue methods are not suitable for detection and 

enforcement of oxathiapiprolin residues or associated metabolites. However, the European 

Multiresidue Method (DFG Method S19) and the QuEChERS Multiresidue Method have shown 

success in some matrices (please see Section 5.1.2 for further details). 

2.2.1.1. PLANT MATRICES

Proposed Enforcement Method. The proposed analytical enforcement method for plant 

commodities is a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method 

that can be used to analyze for parent oxathiapiprolin and the following metabolites 

concurrently: IN-E8S72, IN-WR791, IN-RDG40, IN-Q7H09, IN-SXS67, IN-RZB20 and INRZD74. Crop samples are extracted using a solution of formic acid, water and acetonitrile, and 

diluted with aqueous formic acid solution and methanol. An aliquot of supernatant is 

filtered/centrifuged and analyzed by reverse-phase HPLC-MS/MS in positive ion mode using a 

gradient elution with 0.05% formic acid in water/methanol and 0.01% formic acid in methanol as 

the mobile phases. 

Two ion transitions are available for parent and all seven metabolites. Quantitation was 

performed using the mass transition 222→192 for IN-RZB20; 341→135 for IN-SXS67;

165→65 for IN-RZD74; 207→143 for IN-WR791; 179→65 for IN-E8S72; 556→174 for INRDG40; 556→155 for IN-Q7H09; and 540→163 for oxathiapiprolin. Confirmation was 

performed using the mass transition 222→42 for IN-RZB20; 341→297 for IN-SXS67;

165→135 for IN-RZD74; 207→163 for IN-WR791; 179→40 for IN-E8S72; 556→163 for INRDG40; 556→538 for IN-Q7H09; and 540→500 for oxathiapiprolin.

2.2.1.2. LIVESTOCK MATRICES

The proposed analytical enforcement method for livestock commodities is an HPLC-MS/MS

method that can be used to analyze for parent oxathiapiprolin and the following metabolites 

concurrently: IN-RAB06, IN-RLB67, IN-RDG40 and IN-Q7H09. Residues of oxathiapiprolin 

and metabolites IN-RAB06, IN-RLB67, IN-RDG40 and IN-Q7H09 are extracted from livestock

tissue, milk and egg samples in acetonitrile and hexane using a Genogrinder extractor. 

Following centrifugation, the extracts are diluted with an aqueous formic acid solution and 

methanol and then analyzed. After extraction, the samples are centrifuged and subjected to 

clean-up procedures depending on the matrix and analytes. An aliquot of supernatant is 

filtered/centrifuged and analyzed by reverse-phase HPLC-MS/MS in positive ion mode using a 

gradient elution with 0.05% formic acid in water/methanol and 0.01% formic acid in methanol as 

the mobile phases. 

For residues of parent oxathiapiprolin and each metabolite in livestock matrices, the LOQ was 

0.01 ppm, with a LOD estimated to be 0.003 ppm. Two ion transitions are available for parent 
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and the four metabolites. Quantitation was performed using the mass transition 568→524 for 

IN-RAB06; 572→554 for IN-RLB67; 556→174 for IN-RDG40; 556→155 for IN-Q7H09; and 

540→163 for oxathiapiprolin. Confirmation was performed using the mass transition 568→135 

for IN-RAB06; 572→163 for IN-RLB67; 556→163 for IN-RDG40; 556→538 for IN-Q7H09;

and 540→500 for oxathiapiprolin.

2.2.2 Recommended Tolerances

HED has reviewed the available residue data and has determined the appropriate tolerance levels 

for residues of oxathiapiprolin. HED has concluded that tolerances in livestock commodities are 

not required, given that there is no expectation of finite residues in these matrices. The 

recommended tolerance expression for primary crops and livestock commodities is as follows:

(a) Tolerances are established for residues of the fungicide oxathiapiprolin, including its 

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 

oxathiapiprolin, 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-

thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone, 

in or on the commodity.

For inadvertent residues in rotational crops, the recommended tolerance expression is as follows: 

(d) Indirect or inadvertent residues. A tolerance of 0.10 ppm is established for indirect or 

inadvertent residues of the fungicide oxathiapiprolin, including its metabolites and 

degradates, in or on all other food commodities/feed commodities (other than those 

covered by a higher tolerance as a result of use on growing crops). Compliance with the 

tolerance level is to be determined by measuring only oxathiapiprolin, 1-[4-[4-[5-(2,6-

difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-

(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone, in or on the commodity.
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TABLE 2.2.2. Tolerance Summary for Oxathiapiprolin. 

Commodity Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Grape Berries 0.7 0.70 Grape

Crop Subgroup 1C, Tuberous and 

Corm vegetables

0.01 0.01 Vegetable, tuberous and corm, 

subgroup 1C

Crop Subgroup 3-07A, Bulb Onion 0.04 0.04 Onion, bulb, subgroup 3-07A

Crop Subgroup 3-07B, Green Onion 2 2.0 Onion, green, subgroup 3-07B

Crop Group 8-10, Fruiting 

Vegetables

0.2

Dried fruiting 

vegetables 0.9

0.50

Tomato, dried 3.0

Vegetable, fruiting, group 8-10

Tomato, dried 

Crop Group 9, Cucurbit Vegetables 0.2 0.20 Vegetable, cucurbit, group 9

Crop Subgroup 5A, Head and Stem 

Brassica Vegetables

1.5 1.5 Brassica, head and stem, subgroup 

5A

Crop Subgroup 4A, Leafy Greens 15 15 Leafy greens subgroup 4A

Peas, edible-podded 1 1.0 Pea, edible-podded

Peas, succulent, shelled 0.05 0.05 Pea, succulent shelled

Ginseng root 0.4 0.15 Ginseng

Tobacco, dried leaves

30 None

Tobacco is a non-food use and 

therefore no tolerance is 

recommended. 

Rotational Crops (To be established under a separate section)

All other food commodities/feed 

commodities (other than those 

covered by a higher tolerance as a 

result of use on growing crops)

None 0.10

Being established to harmonize 

with Canada’s PMRA generic 

action MRL. 

2.2.3 Revisions to Petitioned-For Tolerances

As summarized below, some of the proposed tolerances are different from those recommended 

by HED. The registrant should submit a revised Section F in which the proposed tolerances are 

the same as those recommended by HED and the correct commodity definitions are used.

For tobacco, succulent shelled peas, leafy greens, head and stem Brassica vegetables, tuberous 

and corm vegetables, and bulb onion, the proposed and recommended tolerances are identical. 

For grape, green onion, cucurbit vegetables, and edible-podded peas, the recommended 

tolerances include an additional significant figure (such as 1.0 ppm rather than 1 ppm). This is in 

order to avoid the situation where rounding of a residue result to the level of precision of the 

tolerance expression would be considered non-violative (such as 1.4 ppm being rounded to 1 

ppm). 

In the case of Crop Group 8-10, Fruiting Vegetables, the registrant proposed excluding a tomato 

field trial (Trial 18) from the tolerance calculation. If this trial is excluded, all representative 

commodities (bell pepper, non-bell pepper, and tomato) support a crop group tolerance of 0.20 

ppm. However, HED has concluded that this trial cannot be excluded from the tolerance 

derivation (see Section 5.3.1. for further details). With the inclusion of Trial 18, the 
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recommended tomato tolerance becomes 0.50 ppm and, consequently, the recommended Fruiting 

Vegetable Crop Group 8-10 tolerance becomes 0.50 ppm. 

Similarly, with the inclusion of tomato Trial 18, the dried tomato tolerance is also increased from 

the proposed value of 0.9 ppm to the recommended value of 3.0 ppm. This dried fruiting 

vegetable tolerance is based on concentration in sundried tomatoes in the submitted tomato 

processing study. HED would normally not set a tolerance on dried tomato, but has concluded 

that setting this petitioned-for-tolerance is appropriate. Following the HED Processing Factor 

Focus Group (PFFG) Guidance Document (2014, in draft), this tolerance is recommended for 

harmonization. It is also noted that the setting of this dried tomato tolerance is consistent with 

the approach used for other recent global joint reviews (P. Savoia, D422374, 01/15/2015). 

However, HED has concluded that setting a crop group tolerance for all dried fruiting vegetables 

is not appropriate, as our regulations do not currently permit setting a crop group processed 

commodity tolerance (ChemSAC minutes 04/01/2015). 

In the case of ginseng, the registrant submitted four field trials at the GAP proposed use rate and 

two field trials at ~2X the GAP. The registrant indicated that this was done because ginseng is a 

multi-year crop, often being harvested only after multiple growing seasons. For tolerance 

derivation purposes, the registrant has proposed using the residue data from the 2X trials and 

proportionally adjusting the residue data from the 1X trials (where side-by-side treatment was 

not undertaken) to be 2 times higher. Using the 2X trial data, a tolerance of 0.40 ppm is derived. 

However, based on a review of the data and consultation with the global partners, HED has 

concluded that using the 1X data is more appropriate for tolerance-setting, yielding a 0.15 ppm 

recommended tolerance. 

The registrant did not petition for rotational crop tolerances. However, HED has concluded that 

for harmonization purposes, it is appropriate to set a value of 0.10 ppm for inadvertent residues 

in rotational crops. 

2.2.4 International Harmonization

Oxathiapiprolin is the subject of a joint data review with global partners PMRA/Canada and 

APVMA/Australia, with Japan and China/ICAMA acting as observers. There are currently no 

established regulatory levels for any organization, including from Codex. The recommended 

regulatory levels are harmonized among the joint review partners. 

2.3 Label Recommendations

None.

3.0 Introduction

Oxathiapiprolin is a new piperidinyl thiazole isoxazoline fungicide for control of crop diseases 

caused by oomycetes (downy mildew and late blight). 
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3.1 Chemical Identity

Table 3.1. Oxathiapiprolin Nomenclature.

Chemical Structure

Common name Oxathiapiprolin

Identity 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-

2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone

CAS no. 1003318-67-9

Company experimental name DPX-QGU42

IUPAC name 1-(4-{4-[(5RS)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-

yl}-1-piperidyl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

CAS name 1-[4-[4-[5-(2,6-Difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-

piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone

End-use products (EP) Oxathiapiprolin FHG OD (18.7% active ingredient)

Oxathiapiprolin FHG SC (10.2% active ingredient)

ZorvecTM EpicaltrinTM

ZorvecTM EnicadeTM

Oxathiapiprolin is a racemic mixture of IN-Q7N24 and IN-Q7N25, with these structures 

provided below. Chiral chromatographic analysis in livestock and crop matrices confirmed that 

the enantiomeric ratio remained at 1:1 throughout the studies. 

3.2 Physical/Chemical Characteristics

Table 3.2. Physicochemical Properties of Oxathiapiprolin

Parameter Value Reference

Physical State (pure active substance) crystalline solid, powder at 20C. Petition 

Administrative 

Melting point (pure active substance) Materials ~146C

Relative Density at 20°C

(pure active substance) 

1.4645  0.007
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Table 3.2. Physicochemical Properties of Oxathiapiprolin

Parameter Value Reference

Water solubility at 20°C Water 0.1749 g/mL

pH 4 buffer 0.2111 g/mL

pH 7 buffer 0.1844 g/mL

pH 9 buffer 0.2060 g/mL

Solvent solubility at 20°C Acetonitrile 129.9 ± 7.7

Methanol 13.5 ± 0.2

Acetone 162.8 ± 11.3

Ethyl acetate 33.9 ± 0.8

Dichloromethane 352.9 ± 7.9

o-Xylene 5.8 ± 0.1

n-Octanol 0.03 ± 0.00

n-Hexane 0.01 ± 0.00

Vapor pressure at 20°C 1.141 × 10-6

Pa at 20C (8.6 x 10-9 mm Hg)

Henry’s law constant at pH 7, 20°C 3.521 × 10-3

Pa m3/mol or 

3.474 × 10-8atm m3/mol

(negligible escaping tendency from dilute aqueous 

solution)

Dissociation constant (pKa) at 20°C No dissociation at pH 1.0 to 9.1

Octanol/water partition coefficient

Log (KOW) at 20°C

log Kow = 3.6

no pH effect

3.3 Pesticide Use Pattern/Directions for Use (860.1200)

Oxathiapiprolin is a piperidinyl thiazole isoxazoline fungicide developed for control of crop 

diseases caused by oomycetes (downy mildew and late blight). In addition to the proposed use 

on turf and ornamentals, the proposed agricultural crop uses include ginseng, tuberous and corm 

vegetables, bulb vegetables, fruiting vegetables, leafy greens, head and stem Brassica vegetables, 

succulent peas, cucurbits, and tobacco. As previously noted, there is also a proposed tolerance

without a US registration for use on grapes in the EU. A summary of the use directions on crops 

is provided in Table 3.3. 

Two agricultural products are proposed for use in North America (NA) on the various crops: 

ZorvecTM EpicaltrinTM, and ZorvecTM EnicadeTM. 

ZorvecTM EnicadeTM and ZorvecTM EpicaltrinTM are proposed for use on various crops only in 

commercial and farm plantings. ZorvecTM EnicadeTM is formulated as an oil dispersion and 

contains 10.2% ai, whereas ZorvecTM EpicaltrinTM is formulated as a suspension concentrate and 

contains 18.7% ai. Different application methods (foliar and soil) must not be combined when 

protecting a crop during a growing season. For tomatoes, peppers, and edible-peel cucurbits, 

both field and greenhouse uses are proposed, with the use pattern being identical for these uses. 

All of these end-use products may be applied through a variety of application methods including: 

aerial, ground, chemigation, and handheld equipment. 
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Oxathiapiprolin is generally applied 2-4 times per growing season with a minimum 3- to 14-day

retreatment interval depending on crop, pest, and country/region. The single application rates for 

the U.S. use pattern range from 35 to 280 g ai /ha (0.03-0.25 lb ai/A) for crop uses, turf, and 

landscape ornamentals. The maximum seasonal application rate is 560 g ai/ha (0.50 lb ai/A) for 

crop uses, turf, and landscape ornamentals. PHIs range from 0 to 14 days. 

Conclusions. 

The proposed labels are adequate for purposes of evaluating the residue chemistry database. The 

use directions, including application rates, are supported by the available supervised residue 

trials. The label properly denotes the proposed greenhouse uses on tomatoes, peppers, and 

edible-peel cucurbits. 

4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue

A large number of oxathiapiprolin metabolism studies have been submitted including six primary

plant metabolism studies, three livestock metabolism studies, two confined rotational crop 

studies, and two rat metabolism studies. Figure 4.1 provides a summary of the major metabolites 

observed across these studies. 
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Table 3.3. Summary of Proposed Use Pattern. EU = European Union; NA = North America. 

Crop/

Group Region Formulationa

Application 

Typeb

Max # 

Applicationsc

Max Rate/appl

(lb ai/A)

Max Rate/

season

(lb ai/A)

Minimum

Retreatment 

Interval 

(days)

PHI 

(days)

Grape EU OD foliar 2 0.0535 0.107 10 14

Potato EU SE foliar 4 0.01338 0.0535 7 1

Potato NA OD foliar 4 0.0445 0.178 5 5

Cucurbits;

Fruiting Veg EU OD foliar 3 0.02677 0.0803 7 3

Head/Stem Brassicas;

Bulb Veg;

Succulent peas

NA OD foliar 4 0.03125 0.125 5 0

Ginseng NA OD foliar 2 0.25 0.50 14 14

Lettuce EU OD or SE foliar 2 0.01338 0.02677 7 7

Leafy Green Veg NA OD

SC

foliar

soil

4 (foliar)

2 (soil)

0.03125 (foliar)

0.25 (soil)

0.125 (foliar)

0.50 (soil)

3

7

0

Cucurbits;

Fruiting Vegd NA ODSC

foliar

soil

4 (foliar)

2 (soil)

0.03125 (foliar)

0.25 (soil)

0.125 (foliar)

0.50 (soil)

3 or 5

7

0

Tobacco NA OD foliar

soil

4 (foliar)

2 (soil)

0.03125 (foliar)

0.25 (soil)

0.125 (foliar)

0.50 (soil)

5

7

7

a OD = Oil Dispersion. SC = Suspension Concentrate. SE = Suspo-emulsion. b Different application methods (foliar and soil) must not be combined when protecting a crop during 

a growing season. c Maximum # of applications at the maximum single application rate are listed here. For each NA crop use, 2-4 applications are allowed on the labels, with the 

single application rate varying depending on the specific situation, and the maximum seasonal application rate being the same regardless of the number of applications. 

d

For 

tomatoes, peppers, and edible-peel cucurbits, both field and greenhouse uses are proposed, with the use pattern being identical for these uses. 
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

Page 13 of 49

Figure 4.1 – Oxathiapiprolin Comparative Metabolic Pathway. G = Goat; H = Hen; P = 

Plants; R = Rat. 

N O

S

N N

O

N

N

CH3

F

F

F

F

F

OH

N O

S

N N

O

N

N

CH3

F

F

F

F

F

N O

S

N N

O

N

N

CH3

F

F

F

F

F

OH

N O

S

N N

O

N

N

CH3

F

F

F

F

F

N O

S

N N

O

N

N

CH3

F

F

F

F

F

OH

N O

S

N N

O

N

N

F

F

F

F

F

O OHH

N O

S

N N

O

N

N

F

F

F

F

F

OH

OH

N O

S

N N

O

N

N

F

F

F

F

F

OH

N O

S

N N

O

N

N

F

F

F

F

F

O OH

OH

O

N

N

CH3

F

F

F

N O

S

N NH

O

N

N

CH3

F

F

F

F

F

OH

HO

O OH

S

N N

O

N

N

CH3

F

F

F

F

F

NH2

O

N

N

CH3

F

F

F

NH

N

CH3

F

F

F

NH2

O

N

N

F

F

F

OH

OH

O

N

N

F

F

F

OH

NH

N

F

F

F

OH

NH

N

F

F

F

O OH

N

N

O

HO OH

OH

OH

O

OH

F

F

F

N

N N

O OH

O

F

F

F

DPX-QGU42

IN-RDG40

Transient

IN-Q7D41

IN-Q7H09

IN-WR791

IN-E8S72

IN-RAB06

IN-RLB67 IN-RLB27

 H2O

Transient

IN-RLB26

 H, R

G, H, R 

G, H, P, R

G, H, P, R

G, H, P, R

G, H, P, R

IN-RPD37

G, P, R

G, H, R

G, H, P, R

Transient

IN-RLD51

 H, R

Transient

IN-RZB21 IN-RZB20

IN-SXS67

P G, P, R P, (Tranient in Animals)

G, H, P,

IN-KJ552

 P 

H

G, R

P, R

G, R 

P

IN-RZD74
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

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4.1.1 Summary of Plant Metabolism (860.1300)

MRID No. 49011205 (Lettuce – Foliar Application)

MRID No. 49011206 (Lettuce – Soil Application)

MRID No. 49011207 (Grape – Foliar Application)

MRID No. 49011208 (Potato – Foliar Application)

MRID No. 49011209 (Potato – Soil Application)

MRID No. 49011210 (Courgette – Soil Application)

MRID No. 49011236 (Tobacco Pyrolysis)

Data depicting the metabolism of oxathiapiprolin in lettuce, potato, grape, and courgette 

(summer squash) were submitted. The registrant submitted six primary crop metabolism studies, 

three using foliar applications (lettuce, potato, grape) and three using soil applications (lettuce, 

potato, courgette). In the foliar application studies, three 70 g ai/ha (0.062 lb ai/A) foliar spray

applications were made to precultivated lettuce, potato, or grape vines, with a 14-day retreatment 

interval (RTI) and a total application rate of 210 g ai/ha (0.187 lb ai/A). In the soil application 

studies, lettuce seed, seed potatoes, or courgette seed was sown into soil treated with a single 

application of oxathiapiprolin at a nominal application rate of 600 g ai/ha (0.534 lb ai/A). The 

application rates used in the plant metabolism studies adequately represent the GAP rate, with all 

studies being conducted with at least ~1X the GAP rate. Table 4.1.1.1 summarizes the sample 

collection for each plant metabolism study. 

Table 4.1.1.1. Summary of Plant Collection in Oxathiapiprolin Plant Metabolism Studies. 

Plant 

Matrix

Application 

Method

(Comparison to 

U.S. GAPa)

Summary of Plant Collection

Lettuce Foliar

(1.5X)

Whole lettuce plants were sampled immediately after each application once the 

treatment formulations had been allowed to dry (0DAT1, 0DAT2 and 0DAT3), 

immediately before the second and third applications (10DAT1 and 10DAT2) 

and at intervals following the final application (3DAT3, 7DAT3 and 14DAT3). 

Lettuce Soil

(1.1X)

Whole lettuce plants were sampled at three timepoints: 30 days after soil 

treatment (30DAT; BBCH 17), immature (BBCH 45; 44DAT) and at crop 

maturity (BBCH 49; 57DAT). The 30DAT samples were collected as 

contingency samples and were not analyzed. 

Potato Foliar

(1.1X)

Immature potato foliage samples (whole plants) were taken immediately after 

the first application, before and after the second and third (final) applications 

and fourteen days after the final application. The final (maturity) harvest was 

taken 28 days after the final application. Potato tuber samples were taken 

before the third (final) treatment, 14 days after the final treatment (14 DAT3) 

and at final harvest (28 DAT3).

Potato Soil

(Not applicablea)

Whole potato plants were sampled at two timepoints: 37 days after soil 

treatment (37DAT; BBCH 65, immature), and at crop maturity (BBCH 91, 

72DAT). Samples were separated into foliage and tubers at each sampling 

point. 

Grape Foliar

(1.75X)

Grape foliage samples were taken at 0 days after treatment 1 (0DAT1), 

0DAT2, 14DAT2, 0DAT3, 14DAT3 and 76DAT3 (maturity). Berry (fruit) 

samples were taken at 14DAT2, 0DAT3, 14DAT3 and 76DAT3 (maturity). 

CourgetteaSoil

(1.1X)

Whole courgette plants were sampled at two timepoints: 44 days after soil 

treatment (44DAT; BBCH 71, immature), and at crop maturity (BBCH 89, 

79DAT). Samples were separated into foliage and fruit at each sampling point. 

a Comparison of application rate to maximum proposed GAP seasonal use rate (see Table 3.3). Soil application 

methods have not been proposed on potato. Courgette is a cucurbit vegetable. 
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

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The pyrazole, thiazole, or isoxazoline rings were labeled separately in the metabolism studies

(please see structure labeling depiction below). HED has concluded that this labeling was 

sufficient to capture the metabolism of oxathiapiprolin. 

For each of these studies, separate analyses were conducted using two labels. In the metabolism 

studies using foliar application, the radiolabelled forms were [pyrazole-5-

14C]oxathiapiprolin and 

[thiazole-5-

14C]oxathiapiprolin. In the metabolism studies using soil application, [pyrazole-5-

14C] oxathiapiprolin and [isoxazoline-5-

14C]oxathiapiprolin were used. Oxathiapiprolin is a 

racemic mixture of IN-Q7N24 and IN-Q7N25. Chiral chromatographic analysis confirmed that 

the enantiomeric ratio of IN-Q7N24 and IN-Q7N25 remained at 1:1 unchanged throughout the 

studies.

1. [pyrazole-5-

14C]oxathiapiprolin

2. [thiazole-5-

14C]oxathiapiprolin

3. [isoxazoline-5-

14C]oxathiapiprolin

 

For each radiolabel, samples of each plant matrix (immature and mature) were harvested,

homogenized, and analyzed for total radioactive residues by combustion/liquid scintillation 

counting (LSC). Residues were extracted with acetonitrile and acetonitrile:water. In only the 

potato foliar and grape foliar application studies, a range of exhaustive extraction procedures was 

also undertaken (water and acetone extraction; enzymatic, acid and base hydrolyses). The 

extracts were analyzed by HPLC-UV and/or HPLC-MS in order to characterize and identify

oxathiapiprolin residues. The analytical methods used in the studies are acceptable. Samples 

were analyzed within approximately 1 month of harvest; therefore, storage stability data are not 

required to support these studies. All six studies are classified as acceptable guideline studies. 

Table 4.1.1.2 summarizes the major and minor residues observed across the plant metabolism 

studies. Parent and seven metabolites (IN-E8S72, IN-WR791, IN-RDG40, IN-Q7H09, INSXS67, IN-RZB20 and IN-RZD74) were major residues in one or more studies (see Appendix A

for identity and structure of oxathiapiprolin metabolites). For a more detailed summary of the 

plant metabolism study results, please see Appendix B.

In addition, due to the proposed use on tobacco, a tobacco pyrolysis study was submitted (MRID 

N O

S

N

N

O

N

N

F

F

F

F

F

2

1

3
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49011236). The purpose of this study was to examine the distribution of [

14C]oxathiapiprolin 

(DPX-QGU42) pyrolysis products in main stream and side stream cigarette smoke of 

commercial cigarettes spiked with either of two radiolabelled forms, [pyrazole-5-

14C]oxathiapiprolin and [isoxazoline-5-14C]oxathiapiprolin. The pyrolysis of oxathiapiprolin in 

cigarettes resulted primarily in degradation to 14CO2, averaging a total of 13.5 and 14.4% of the 

applied radioactivity for [pyrazole-5-

14C] and [isoxazoline14C] label sets, respectively. 

Unchanged oxathiapiprolin was the major component present in the butt and filter extracts, 

averaging 49.6 and 58.1% of the applied radioactivity in the [pyrazole-5-

14C] and [isoxazoline-5-

14C] labels, respectively. The remaining radioactivity was recovered as bound residues and 

minor volatile components, none representing >2.9% of the applied dose. This study has 

adequately characterized the tobacco pyrolysis of oxathiapiprolin and is classified as acceptable 

guideline. 

Conclusions. 

The submitted primary plant metabolism studies and the tobacco pyrolysis study are considered 

to be acceptable guideline studies. 
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

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Table 4.1.1.2. Summary of Plant Metabolism Study Results. Values listed are the maximum % TRR observed in each study across both 

labels used, with the application method listed in parentheses for each matrix. Italicized compounds were tested for in the crop field 

trials. Minor metabolites (<10% TRR) are shaded in grey. 

Lettuce 

(Foliar)

Lettuce 

(Soil)

Potato 

Foliage 

(Foliar)b

Potato 

Foliage

(Soil)

Potato 

Tubers

(Soil)

Grape 

Foliage 

(Foliar)

Grape 

Berries 

(Foliar)

Courgette 

Foliage (Soil)

Courgette 

Fruit (Soil)

Oxathiapiprolin 85 59 9 7 98 74 24 <1

IN-Q7H09 5 2 5 2 19

IN-RDG40 <1 2 3

IN-RZB20 7 13 12 6 17 3

IN-WR791 30 13 25 1 19 28 74

IN-RZB21/

IN-RDZ74a

21 19 6 13 4

IN-E8S72 21 12 14 2 14 24 5

IN-SX67 4 6 7 4 4 7 4

IN-Q7D41 1 2 2 <1

IN-KJ552 3 4 7 <1 1 3 3

IN-RAB06 2 2

IN-Q9L80 <1 <1

IN-Q9PS10 1 <1

IN-Q9R70 -- <1

a

In most of the plant metabolism studies, similar metabolites IN-RZB21 and IN-RDZ74 could not be resolved from one another for identification purposes. 

They were therefore reported together. Only IN-RDZ74 was tested for in the crop field trials. 

b Low levels of extractable radioactivity in potato tuber extracts (≤0.012 ppm) were associated with plant natural products, thus precluding further analysis of 

potato tuber residues.
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4.1.2 Summary of Livestock Metabolism (860.1300)

MRID No. 49011148 Poultry Metabolism - Oxathiapiprolin

MRID No. 49011147 Lactating Ruminant (Goat) Metabolism - Oxathiapiprolin

MRID No. 49011211 Lactating Ruminant (Goat) Metabolism – Metabolite IN-SXS67

Data depicting the metabolism of oxathiapiprolin in laying hens and lactating goats were submitted. A 

second goat metabolism study was also performed using metabolite IN-SXS67. IN-SXS67 and related 

metabolite IN-E8S72 were either major or minor metabolites in the primary and rotational crop field trial 

studies. However, IN-SXS67 was not observed in the livestock metabolism studies and IN-E8S72 was 

only seen in a single livestock matrix (goat liver). Therefore, the additional goat metabolism study was 

conducted to further elucidate the breakdown of IN-SXS67 in livestock. 

Oxathiapiprolin, radiolabeled in the thiazole or pyrazole ring, was administered orally via gelatin 

capsule to the test animals. This radiolabelling is considered sufficient to capture the livestock 

metabolism of oxathiapiprolin. Study parameters are summarized in Table 4.1.2.1, below.

Table 4.1.2.1. Summary of Hen and Goat Metabolism Studies Experimental Parameters.

Experimental Parameter Laying Hens Lactating Goats

Number of Animals 5 per radiolabel position 1 per radiolabel position (Oxathiapiprolin 

study)

1 total in pyrazole ring (IN-SXS67 study)

Dosing Period 14 days 7 days

Dosing Level ~2.4 mg/day 

(Pyrazole label - 17.4 mg/kg feed/day)

(Thiazole label – 17.8 mg/kg feed/day)

~36X MRDB

Oxathiapiprolin Study

Pyrazole: ~21 mg/day (14.2 mg/kg feed/day)

Thiazole: ~18 mg/day (14.3 mg/kg feed/day)

~174X MRDB

IN-SXS67 Study

Pyrazole: ~27 mg/day (18.95 mg/kg feed/day)

Egg/Milk Collection Daily (morning and evening) Daily (morning and evening)

Excreta Collection Daily (morning, prior to dosing) Daily (morning, prior to dosing)

Time from Last Dose to 

Sacrifice

~6 hours 12 hours

Tissues Harvested and 

Analyzed

Muscle (breast and thigh)

Liver

Fat (omental and subcutaneous)

Carcass collected and frozen until study 

completion (but not analyzed)

Muscle (Oxathiapiprolin study: loin, hind, and 

fore quarter; IN-SXS67 study: loin and flank)

Liver

Kidney

Fat (omental, subcutaneous, renal)

Carcass collected and frozen until study 

completion (but not analyzed)

Sample Storage 

Duration

<6 months <4 months (Oxathiapiprolin study)

57 days (IN-SXS67 study)

In the oxathiapiprolin hen metabolism study, triplicate aliquots of each of the homogenized 

matrices were taken and analyzed by combustion/LSC or solubilised for LSC. Daily excreta 

were composited separately by taking 5% from Days 1-14 collections for each radiolabel group; 

eggs were composited by taking 10% of whole egg from Days 10-14 for each radiolabel group. 

Subsamples (ca. 30-50 g) of composite samples of tissues, whole egg and excreta were prepared 

for metabolite extraction and analysis. Tissue and excreta samples were extracted with 

acetonitrile and acetonitrile/water (4/1 and 1/1, v/v). Whole egg and fat samples were extracted 

with dichloromethane, acetonitrile and acetonitrile/water (4/1, v/v). The resulting extracts were 
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

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combined by matrix, concentrated, and analyzed by LSC and HPLC. All liver post-extracted 

solids (PES) were further treated with protease (37°C; 120 hr) to release unextracted residues. 

The samples were extracted with acetonitrile after protease digestion and the resulting extracts 

analyzed by LSC and HPLC. All extracts were stored at -20°C prior to HPLC analysis.

In the goat metabolism study for oxathiapiprolin, tissue and fat samples were homogenized in 

dry ice. Triplicate aliquots of each matrix were then taken and analyzed by combustion/LSC or 

solubilized for LSC. Equal amounts of feces, urine, and milk from Days 1-7 were pooled by 

radiolabel. Subsamples (ca. 30-100 g) of tissues, milk and feces were prepared for metabolite 

extraction and analysis. Samples were extracted with dichloromethane, acetonitrile and 

acetonitrile/water (4/1, v/v). The resulting extracts were combined by matrix, concentrated and 

analyzed by LSC and HPLC. The liver PES from both goats were further treated with protease 

(37°C; 120 hr) to release unextracted residues. The samples were extracted with acetonitrile 

after protease digestion and the resulting extracts analyzed by LSC and HPLC. All extracts were 

stored at -20°C prior to HPLC.

In the goat metabolism study for metabolite IN-SXS67, tissue and fat samples were 

homogenized in dry ice. Liver, kidney, muscle and fat samples were mixed with tissue 

solubilizer, and incubated at 50°C overnight. Acetic acid and LSC cocktail were added, and the 

samples were analyzed by LSC. Aliquots of milk, urine, and cage wash samples were analyzed 

for total radioactivity by LSC. Aliquots of the feces and GI tract samples were subjected to 

combustion analysis and LSC. Individual aliquots (30-50 g) of tissues and feces (Day 1-7 

composite) samples were extracted with acetonitrile/water (1/1, v/v) followed by acetonitrile. 

Radioactivity remaining in the pellets was determined by combustion analysis following the final 

extraction. The combined extracts were concentrated, and the radioactive content was 

determined by LSC analysis. Since coextractives in the liver sample made further concentration 

difficult, the liver extracts were purified by C18 solid phase extraction prior to HPLC-MS 

analysis.

Results – Poultry. Oxathiapiprolin and metabolites were readily eliminated in the hen excreta 

(including cage wash), where 95-100% of the dose was recovered. Total radioactive residues 

(TRR) plateaued within 10-11 days in whole eggs. Transfer of radioactive residues to the eggs 

was very low with 0.02% or less of the dose eliminated via this route over the 14 days. 

Approximately 0.02% or less of the dose was found in the liver, muscle, and fat 6 hours after the 

last dose indicating no bioaccumulation potential. Total radioactive residues in the liver were 

0.096 ppm and 0.103 ppm for the [pyrazole-5-

14C] and [thiazole-5-14C]oxathiapiprolin dosed 

hens, respectively. Total residues were below 0.030 ppm in whole eggs, muscle, and fats. 

Greater than 45% of the radioactivity in the tissues and eggs could be extracted, with the 

majority of residues identified or characterized. Intact oxathiapiprolin was detected in most 

tissues and eggs. Metabolites present in the tissues and eggs included IN-RAB06, IN-QFD61, 

IN-RDG40, IN-Q7H09, and IN-Q7D41.

 

Table 4.1.2.2 provides a summary of the hen metabolism study results. For a detailed 

breakdown of these results, please see Appendix E. Since the results across the labels were 

similar, Table 4.1.2.2 presents the highest residue identified across the labels for each matrix. 

Table 4.1.2.2. Summary of Identified Residues from Oxathiapiprolin Hen Metabolism 
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Study in %TRR (ppm). For each compound, matrix and across both labels studied, 

the maximum observed %TRR and ppm residue is listed. ND = Not detected. 

Whole eggs Liver Abdominal fat Skin with fat

Oxathiapiprolin

21.9

(0.003)

8.2

(0.008)

66.2

(0.01)

36.9

(0.004)

IN-RAB06

ND 13.5

(0.014)

ND ND

IN-QFD61

ND 9.8

(0.01)

ND ND

Hydroxy metabolitesa

4.8

(0.001)

7.6

(0.007)

15.4

(0.005)

33.2

(0.004)

IN-Q7D41

7.1

(0.001)

ND 4.9

(0.002)

10.1

(0.001)

a

 Reference standards for hydroxyl metabolites IN-RDG40 and IN-Q7H09 were not fully resolved in the majority of 

tissue extracts using the routine HPLC method.

Results – Goats – Oxathiapiprolin Study. The study results showed that oxathiapiprolin and 

metabolites are readily eliminated in the urine and feces where 84.3-86.4% of the dose (including 

cage wash) was recovered. Total radioactive residues plateaued within 5 days in milk. Transfer 

of radioactive residues to the milk was very low with 0.2% or less of the dose eliminated via this 

route over the 7 days. Less than 1.2% of the dose was found in the liver, kidney, muscle, and fat 

combined at sacrifice 12 hours after the last dose, indicating that there is no bioaccumulation 

potential. Approximately 94.0-99.6% of the total dose was recovered when the radioactivity 

found in gastrointestinal contents (8.4-12.3% dose) was included. 

Table 4.1.2.3 provides a summary of the identified residues in the oxathiapiprolin goat 

metabolism study. For a more detailed breakdown of these results, please see Appendix E. 

Since the results across the labels were similar, Table 4.1.2.3 presents the highest residue 

observed across the labels for each matrix. Total radioactive residues in liver and kidneys were 

0.857 and 0.087 ppm for the [pyrazole-5-

14C]oxathiapiprolin dosed goat, and 0.834 and 0.073 

ppm for the [thiazole-5-

14C]oxathiapiprolin dosed goat, respectively. Total residues were below 

0.029 ppm in milk, muscle, and fat. Greater than 52.4% of the radioactivity in the tissues and 

milk was extracted, with the majority of residues identified or characterized. Residues of 

unmetabolized oxathiapiprolin were detected in most tissues including milk (at ca. 0.002 ppm). 

Metabolites present at greater than 5% of the TRR in the various tissues and/or milk included INE8S72, IN-RAB06, IN-RLB67, IN-QFD61 IN-RDG40, IN-Q7H09, and IN-Q7D41. 

Oxathiapiprolin was present at 59.0% and 56.4% dose in the feces from [pyrazole-5-

14C]- and 

[thiazole-5-

14C]oxathiapiprolin goats.

Table 4.1.2.3. Summary of Identified Residues from Oxathiapiprolin Goat 

Metabolism Study in %TRR (ppm). For each compound, matrix and across both 

labels studied, the maximum observed %TRR and ppm residue is listed. ND = Not 
Oxathiapiprolin Summary of Analytical Chemistry and Residue Data Barcode D426128

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detected. 

Milk Liver Kidney Muscle Fat (all matrices)

Oxathiapiprolin

10.8

(0.002)

11.8

(0.114)

13.8

(0.011)

42.6

(0.004)

57.6

(0.016)

Hydroxy Metabolitesa

4

(0.001)

13.3

(0.129)

20.6

(0.013)

30.1

(0.004)

25.7

(0.007)

IN-E8S72 ND ND

24.4

(0.021) ND ND

IN-Q7D41

2.9

(0.001)

0.9

(0.008) ND

5.5

(0.001)

15.3

(0.004)

IN-QFD61

8.6

(0.002)

0.6

(0.004) ND ND ND

IN-RAB06

11.1

(0.002)

1.8

(0.016)

4.8

(0.003) ND ND

IN-RLB67 ND

5.2

(0.051) ND ND ND

a

 Reference standards for hydroxy metabolites IN-RDG40 and IN-Q7H09 were not resolved in the routine HPLC 

method. A modified method was used during LC-MS analysis to resolve these components in liver, however this 

was not done in other tissues due to low levels detected. This method showed a further 2 minor unidentified 

hydroxy components were also present at similar retention time to IN-RDG40 and IN-Q7H09. 

Results – Goat – Metabolite IN-SXS67 Study. In the IN-SXS67 goat metabolism study, 

[Pyrazole-5-14C]IN-SXS67 was administered to a lactating goat at an average dose of 18.95 

mg/kg feed. IN-SXS67 and the metabolite IN-E8S72 are readily eliminated with 59.1% of the 

administered dose recovered in the feces and 26.0% in the urine. Edible tissues and milk contain 

negligible amounts of radioactivity (<0.1% of the AD). An additional 12.5% of the dose was 

found in the GI tract at sacrifice. Total radioactive residues in milk plateaued within two days 

(0.002-0.004 ppm). Transfer of radioactive residues to the milk was very low, with less than 

0.02% of the dose eliminated via this route over the seven days. Samples of milk fat and skim 

milk prepared from whole milk contained equal concentrations of residues (0.003 ppm), 

indicating no selective partitioning of IN-SXS67 to the lipid fraction of milk. Less than 0.1% of 

the dose was found in the liver, kidney, muscle, and fat combined at sacrifice six hours after the 

last dose, indicating that there is no bioaccumulation potential. Residues in fat were low (0.002-

0.006 ppm) and no selective accumulation of IN-SXS67 residues in the various fat types 

(omental, subcutaneous and renal fat) was observed. Kidney and liver contained total 

radioactive residues of 0.483 ppm and 0.038 ppm, respectively. Overall, 97.7% of the 

administered dose was recovered.

IN-SXS67 was the principal component of the residue in kidney (0.278 ppm, 57.6% of the TRR) 

and liver (0.030 ppm, 78.9% of the TRR). IN-E8S72 was present at 0.186 ppm (38.5% of the 

TRR) in kidney, and 0.005 ppm (13.2% of the TRR) in liver. IN-SXS67 and metabolite INE8S72 were the only components in urine and feces. IN-E8S72 was the major component of the 

excreted residues (51.7% of the dose), with IN-SXS67 accounting for 30.6% of the dose. 

Overall, IN-SXS67 metabolized primarily to IN-E8S72. The total radioactive residues in the 

milk, muscle and fat were low. There was no significant potential for accumulation of INSXS67 or its biotransformation products.
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Conclusions. 

The submitted livestock metabolism studies are considered to be acceptable guideline studies

4.1.3 Summary of Confined Rotational Crops (860.l850)

MRID No. 49011241 Confined Rotational Crop Study – 210 g ai/ha

MRID No. 49011240 Confined Rotational Crop Study – 600 g ai/ha

Two confined rotational crop studies were conducted. One study had soil treated at 210 g ai/ha 

(0.187 lb ai/A; ~0.4X), the other at 600 g ai/ha (0.534 lb ai/A; ~1X). The soil in each study was 

then aged 30, 120 and 365 days prior to planting lettuce, turnips, and wheat at each aging period. 

A single application of either [pyrazole-5-14C]oxathiapiprolin, [thiazole-5-

14C]oxathiapiprolin or 

[isoxazoline-5-

14C] oxathiapiprolin was used, with all analyses from each study submitted for 

both labels. 

In the 210 g ai/ha study, the TRR was highest in the food commodities in the soil treated with 

[Py14C]-label: 0.258 ppm (grain), 0.028 ppm (lettuce) and 0.023 ppm (turnip tubers). 

Oxathiapiprolin was a minor residue (<0.01 ppm) in the food commodities. Metabolites 

included IN-WR791 (≤0.098 ppm), IN-E8S72 (≤0.039 ppm), IN-RZB20 (≤0.022 ppm), INRZB21/IN-RZD74 (≤0.012 ppm), IN-SXS67 (≤0.011 ppm) and, in immature lettuce, IN-Q7D41 

(≤0.01 ppm). Low levels of radioactivity were also associated with multiple unidentified 

components, characterized fractions and the terminal unextracted residues (all individually ≤0.01 

ppm). 

In the 560 g ai/ha study, the TRR were highest in the food commodities from soil treated with 

[Py-14C]: ≤0.191 ppm (grain), ≤0.036 ppm (lettuce) and ≤0.020 ppm (turnip tubers). 

Oxathiapiprolin was a minor residue (≤0.001 ppm) in the extracts of food commodities. 

Metabolites included IN-WR791 (≤0.047 ppm), IN-E8S72 (≤0.019 ppm), IN-RZB20 (≤0.017 

ppm), IN-RZB21/IN-RZD74 (≤0.011 ppm), IN-SXS67 (≤0.015 ppm), and IN-KJ552 (≤0.004 

ppm). Radioactivity was also detected in multiple unidentified components, unprofiled fractions 

and the terminal unextracted residues (all individually ≤0.05 ppm). 

The maximum %TRR observed in each crop matrix across studies, labels, and plant back 

intervals is summarized in Table 4.1.3. The minimum and maximum %TRR is also listed in 

Appendix A, which includes the chemical structure of each observed metabolite. For a detailed 

breakdown of these confined rotational crop study results, please see Appendix C. 

Conclusions. 

The confined rotational crop studies are considered to be acceptable guideline studies. 
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Table 4.1.3. Summary of Confined Rotational Study Results. Values listed are the maximum % TRR observed across studies 

and both labels used. Italicized compounds were tested for in the crop field trials. Minor metabolites (<10% TRR) are shaded 

in grey. 

Wheat 

grain

Wheat 

forage Wheat hay Wheat straw

Turnip 

tubers

Turnip 

foliage

Lettuce 

leaves

Oxathiapiprolin and 

non-polar 

metabolites 1.9 6.1 16.4 12.5 15.2 1.7 5.8

IN-E8S72 20.1 12.1 16.7 13.5 18.6 72.7 48.1

IN-WR791 37.7 42.2 18.7 8.3 48.8 52.1 34.3

IN-SXS67 11.8 58.8 55.7 57.2 7.2 9.9 5.2

IN-RZB20 13.2 55.1 42.5 27 4 11.6 13.9

IN-RZB21/

IN-RZD74b

8.6 13.5 14.4 15 13.7 32 20.8

IN-Q7H09 ND ND 4.2 8.2 ND ND ND

IN-RDG40 ND ND ND 4.8 ND 0.5 ND

IN-KJ552 2.9 7.9 4.6 4.2 9.9 2.5 4.9

IN-QPS10 ND ND ND 12.4 ND ND ND

IN-Q7D41 ND ND ND ND ND ND 6

a

 In some cases, the HPLC system did not separate oxathiapiprolin from non-polar reference standards IN-Q7H09, IN-RDG40, IN-Q9R70, IN-RAB06 and INQ7D41. 

b

In most cases, similar metabolites IN-RZB21 and IN-RDZ74 could not be resolved from one another for identification purposes. They were therefore reported 

together. Only IN-RDZ74 was tested for in the primary and rotational crop field trials.
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4.1.4 Summary of Metabolites and Degradates

The nature of the residue in the proposed crops and livestock is adequately understood for 

regulatory purposes. The confined rotational crop study may be interpreted as being reflective of 

results that would be expected from studies designed to examine metabolism in target crops

following early season soil application. As such, metabolism data are available from the root 

vegetable, leafy crop, fruit, and cereal crop categories. The results of those studies are all similar 

and cover four of the five crop categories (pulses/oilseeds are not covered). A summary of the 

metabolites and degradates of oxathiapiprolin in plant, livestock, and environmental matrices is 

included in Appendix A. 

4.2 Comparison of Metabolic Pathways

A comparative metabolic pathway of oxathiapiprolin (DPX-QGU42) is presented in Figure 4.1, 

with the matrix-specific metabolic pathways presented in Appendix F. The major metabolic 

pathways of oxathiapiprolin in the monogastric hen and rat, ruminant goat, and plants occurred 

primarily through hydroxylation and further oxidation reactions. Hydroxylation of the phenyl 

moiety formed two metabolites, IN-Q7H09 and IN‐RDG40. A transitory metabolite (INRPD37) may have formed by hydroxylation of the pyrazole methyl carbon, which further 

oxidized to carboxylic acid, IN-RAB06, mainly in animals. The cleavage of the bond between 

piperidine ring nitrogen and pyrazole moiety of IN-RAB06 gave IN-E8S72, which formed an Nglucoside conjugate in the plants from foliar (mainly grape vines) as well as soil treatments. 

Hydrolysis of the piperidine-2-carbon followed by ring opening may have resulted in formation 

of IN-RZB21 (amide), which further hydrolyzed to IN-RZB20 in the plants. IN-RZB20 via 

multiple metabolic reactions may also have yielded IN-E8S72.

Hydroxylation in the isoxazoline ring followed by dehydration resulted in a non-polar 

metabolite, IN-Q7D41 in both animals and plants. Hydrolysis of the isoxazoline ring formed a 

transitory metabolite, which further degraded to IN-RLD51 in the hen. Piperidine-2-carbon 

hydroxylation followed by ring opening gave rise to IN‐RLB26, which may have further 

degraded through a transient amide, which served as a precursor to IN‐WR791. Further 

degradation of IN-WR791 gave rise to IN-KJ552 mainly in the plants grown in the 

oxathiapiprolin treated soils. Dihydroxylated metabolites, such as IN-RLB67 and IN-RLB27, 

were also observed in the animals. Additionally, several minor metabolites were tentatively

identified in the animals and plants and not discussed here as they were present in low levels.

4.3 Residues of Concern Summary and Rationale

ROCKS Report: D425280, I. Negrón-Encarnación, 04/29/2015

The Residues of Concern Knowledgebase Subcommittee (ROCKS) met on 22 January 2015 to 

discuss the residue definitions for oxathiapiprolin. Their recommendations are summarized 

below. 

Radiolabelling approach: The ROCKS was asked by the oxathiapiprolin team to weigh in on 

the registrant rationale for radiolabelling only three (pyrazole, thiazole or isoxazoline) of the five 

rings of oxathiapiprolin. The registrant indicated that the most stable positions of radiolabels 
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were selected based on the results of a rat metabolism study. This study did not show significant 

cleavage of the bonds between the isoxazoline and difluorophenyl rings, or between the thiazole 

and piperidine rings, or between thiazole and isoxazoline moieties. Studies with plants and 

animals showed that the bridge between the pyrazole and piperidine moieties was labile; 

however, metabolism studies with the radiolabeled pyrazole were conducted and the 

transformation of the pyrazole moiety was followed. Overall, the ROCKS did not identify

specific concerns with the selection of the radiolabels of oxathiapiprolin. 

Oxathiapiprolin is 1-[4-[4-[5-(2,6-Difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-

methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-ethanone

1 Refer to Appendix A for the names and/or chemical structures of the metabolites/degradates.

Hazard Considerations

In the toxicity studies for oxathiapiprolin, no treatment related effects were seen in any species at 

doses up to the limit dose (1000 mg/kg/day). The only treatment related effects were observed in 

offspring in rat reproduction studies at doses above the limit dose. Human exposure at this level 

is not anticipated in conjunction with the use of products containing oxathiapiprolin in 

accordance with proposed labels. Due to the limited toxicity in the oxathiapiprolin toxicological 

database, HED has determined that a quantitative risk assessment is not needed (i.e., no doses or 

endpoints were selected for risk assessment). Therefore, a qualitative human health risk 

assessment will be conducted to support the proposed uses of oxathiapiprolin. Consequently, 

HED has concluded that residues of concern are only required for tolerance enforcement and do 

not need to be set for risk assessment, as there will not be a quantitative dietary risk assessment. 

Due to the lack of toxicity from oxathiapiprolin, USEPA would normally grant a tolerance 

exemption for this chemical. However, given that this chemical is being assessed as part of a 

global joint review and is intended to be registered in additional countries, the Agency is setting 

tolerances for harmonization purposes. 

Exposure Considerations

Primary Crops: For the vast majority of crops, parent oxathiapiprolin was the primary residue 

present in field trial samples across all crop field trials. For potato, it is noted that there were no 

quantifiable residues of parent oxathiapiprolin or any metabolite at the proposed PHI or at any

PHI tested. Therefore, oxathiapiprolin is recommended as a residue of concern for tolerance 

enforcement on primary crops. 

Rotational Crops: Average residues of metabolites IN-E8S72 and IN-SXS67 ranged from 

Table 4.3. 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 for Compliance 

Monitoring

Plants Primary Crop Not applicable. Oxathiapiprolin

Rotational Crop Not applicable. Oxathiapiprolin 

Livestock Ruminant Not applicable. Oxathiapiprolin

Poultry Not applicable. Oxathiapiprolin

Drinking Water Not applicable. Not Applicable
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<LOQ in several commodities up to 0.30 ppm in wheat hay. In general, the metabolites INE8S72 and IN-SXS67 were at higher concentrations than parent oxathiapiprolin and more 

consistently observed across all crops. Given that tolerances are being set solely for the purposes 

of harmonization with global partners, HED has concluded that it is appropriate to align the 

residue of concern for tolerance enforcement with the global partners. PMRA has set the residue 

of concern as parent oxathiapiprolin only in rotational crops and will be setting a generic action 

MRL of 0.10 ppm on all crops not currently proposed on the label. This generic action MRL of 

0.10 ppm will be used to provide coverage for inadvertent residues in rotational crops. HED 

concludes that this approach is adequate for the purposes of tolerance enforcement in rotational 

crops and that this aligned approach will avoid future trade irritants with global partners. 

Ruminants: There is no expectation of finite residues for ruminant matrices and no ruminant 

tolerances have been proposed at this time. Parent oxathiapiprolin was a major residue across all 

goat matrices; therefore, it is considered an adequate indicator of misuse. The ROCKS 

recommends parent only for tolerance enforcement. This decision may need to be revisited 

depending on the results of any future submissions of ruminant feeding studies.

Poultry: There is no expectation of finite residues for poultry matrices and no poultry tolerances 

have been proposed at this time. Parent oxathiapiprolin is recommended as the residue of 

concern for tolerance enforcement on poultry commodities. This decision may need to be 

revisited in the future if uses resulting in a higher livestock dietary burden are proposed. 

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1.1 Data Collection Methods

MRID No. 49011136 (Plants)

DuPont Method 30422, Supplement No.1, was used for all crop residue studies. Table 5.1.1 

summarizes the analytical method parameters. 

Table 5.1.1. Summary of Oxathiapiprolin Analytical Method for Plant Commodities.

Method ID DuPont-30422, Supplement No. 1, Analytical Method for the Determination of

DPX-QGU42 and Metabolites in Crops Using LC/MS/MS

Analyte(s) Oxathiapiprolin and metabolites (IN-Q7H09, IN-RDG40, IN-E8S72, IN-RZB20, 

IN-RZD74, IN-SXS67, and IN-WR791) 

Extraction 

Solvent/Technique 12:4:0.1 acetonitrile:water:formic acid

Cleanup Strategies 

(If Needed) Filtration through a EnviTM-Carb SPE 6 cc 250 mg cartridge 

Chromatography HPLC: Waters Acquity HSST3, 2.1 mm  50 mm, 1.8 m particle size diameter

Detection Triple quadrupole mass spectrometer (MS/MS) - using an electrospray (ESI) interface

LOQ 0.010 mg/kg

In analytical method DuPont-30422 Supplement 1 residues of oxathiapiprolin and metabolites 

IN-SXS67, IN-RZB20, IN-RZD74, IN-E8S72, IN-WR791, IN-RDG40, and IN-Q7H09 are 

extracted from crop samples using a solution of formic acid, water and acetonitrile, and diluted 
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with aqueous formic acid solution and methanol. An aliquot of supernatant is 

filtered/centrifuged and analyzed by reverse-phase HPLC-MS/MS in positive ion mode using a 

gradient elution with 0.05% formic acid in water/methanol and 0.01% formic acid in methanol as 

the mobile phases. The analytes are determined via LC-MS/MS. 

For some matrices, ion suppression or matrix interference was observed. For these matrices, a 

solid-phase extraction (SPE) clean-up using a graphitized carbon cartridge was used. Due to the 

selectivity of graphitized carbon cartridges, the polar (IN-SXS67, IN-RZB20, IN-RZD74, INWR791 and IN-E8S72) and non-polar (IN-RDG40, IN-Q7H09 and oxathiapiprolin) compounds 

were eluted separately. For these matrices, the analysis was divided into two injections, polar 

compounds and non-polar compounds. For the analysis of oranges, grapes, wheat straw and 

canola, the SPE clean-up was used for the polar compounds. For the analysis of ginseng, the 

SPE clean-up was used for the analysis of polar and non-polar compounds.

Method validation results showed that mean recoveries for residues of oxathiapiprolin and 

metabolites IN-SXS67, IN-RZB20, IN-RZD74, IN-E8S72, IN-WR791, IN-RDG40, and INQ7H09 in canola, grape, orange, tomato, potato, ginseng, wheat grain and wheat straw were 76-

115% at fortification levels of 0.01 and 0.10 ppm.

Confirmatory data with a second ion using method Dupont-30422 Supplement 1 for all eight 

analytes were submitted with Dupont-30422 Supplement 2. The data were reported separately, 

but were generated simultaneously with the DuPont-30422 Supplement 1 study. Using 

confirmatory ion transitions, mean recoveries for residues of oxathiapiprolin and metabolites INSXS67, IN-RZB20, IN-RZD74, IN-E8S72, IN-WR791, IN-RDG40, and IN-Q7H09 in canola, 

grape, orange, tomato, potato, ginseng, wheat grain and wheat straw were 76-117% (except three 

recovery values of 54%, 69% and 127%) at fortification levels of 0.01 and 0.10 ppm.

Two ion transitions are available for parent and all seven metabolites. Quantitation was 

performed using the mass transition 222→192 for IN-RZB20; 341→135 for IN-SXS67;

165→65 for IN-RZD74; 207→143 for IN-WR791; 179→65 for IN-E8S72; 556→174 for INRDG40; 556→155 for IN-Q7H09; and 540→163 for oxathiapiprolin. Confirmation was 

performed using the mass transition 222→42 for IN-RZB20, 341→297 for IN-SXS67, 165→135 

for IN-RZD74, 207→163 for IN-WR791, 179→40 for IN-E8S72, 556→163 for IN-RDG40, 

556→538 for IN-Q7H09, 540→500 for oxathiapiprolin.

The method underwent ILV by different laboratories, which showed similar results to the 

validation tests. Oxathiapiprolin, IN-SXS67, IN-E8S72 and IN-WR791 were analyzed in wheat 

grain, grape and tomato. Residues of oxathiapiprolin, IN-SXS67, IN-RZB20, IN-RZD74, INE8S72, IN-WR791, IN-RDG40, and IN-Q7H09 were analyzed in carrot roots, spinach leaves, 

hops, wheat (forage, grain, straw), potato, potato chip, grape, grape dry pomace, tomato, tomato 

juice, spinach, broccoli, whole pepper, dried soybean seed, dried beans, dry bulb onion, dried 

ginseng and dried tobacco leaves. Overall, mean ILV recoveries were 71-120% at fortification 

levels of 0.01 and 0.10 ppm.

The residue profiles obtained by extracting bio-incurred residues of radiolabelled test substance 

from samples of lettuce, grape berries and wheat grain using the DuPont-30422 Supplement 1 
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extraction procedures were compared with those obtained for the same samples in the plant 

metabolism study. The levels of oxathiapiprolin and metabolites obtained using Method 

DuPont-30422 Supplement 1 were within 80-120% of those found in the metabolism study, 

indicating that Method DuPont-30422 Supplement 1 provides acceptable extraction efficiency.

The method LOQ, defined as the lowest limit of method validation, is 0.01 ppm for each analyte. 

The analytical method DuPont-30422 Supplement 1 is considered suitable for enforcement 

purposes of oxathiapiprolin and metabolites IN-SXS67, IN-RZB20, IN-RZD74, IN-E8S72, INWR791, IN-RDG40, and IN-Q7H09 in high water, high acid, high starch, high oil and high 

protein content matrices.

Conclusions.

The analytical method used for data collection has been adequately validated. The results are 

within generally recognized limits for analytical methods (mean recoveries between 70 and 

120% with a relative standard deviation of ≤ 20%). Furthermore, the solvent used for extraction 

was shown to efficiently extract incurred residues in the metabolism studies. 

5.1.2 Multi-Residue Methods (860.1360)

MRID No. 49011133 (DFG Method S19)

MRID No. 49011142 (QuEChERS)

MRID No. 49011143 (U.S. FDA MRM testing)

U.S. Multiresidue Methods. FDA multiresidue protocols were evaluated for their ability to 

analyze for oxathiapiprolin and the metabolites IN-SXS67, IN-E8S72, and IN-WR791. 

Protocols A, B, and C were not suitable because of poor sensitivity and/or because of 

degradation in the gas chromatography (GC) detector. Without an appropriate determinative 

step from Protocols A, B, or C, the remaining Protocol D, E, and F testing was suspended as per 

the PAM protocol. 

European Multiresidue Method (DFG Method S19). The European multiresidue analytical 

method DFG S19 has been successfully validated for the analysis of oxathiapiprolin and 

metabolites IN-RZB20, IN-RZD74, IN-E8S72, IN-WR791, IN-RDG40, and IN-Q7H09 in high 

water, high acid and high starch content crop matrices in terms of specificity, linearity, precision, 

accuracy and LOQ. The method is considered acceptable for enforcement purposes in terms of 

materials, equipment and analysis time. It is not suitable for the analysis of metabolite IN-SXS67 

in crop matrices, or for the detection of oxathiapiprolin and metabolites IN-RDG40 and INQ7H09 in high oil content matrices.

Method S19 was also found to be successful for the determination of oxathiapiprolin and 

metabolites IN-Q7H09, IN-RDG40, IN-RLB67, and IN-RAB06 in livestock matrices (milk, 

meat (muscle), liver, fat and eggs). 

QuEChERS Multiresidue Method. The multiresidue analytical method QuEChERS has been 

successfully validated for the analysis of oxathiapiprolin in high water, high acid, high starch and 

high oil content crop matrices in terms of specificity, linearity, precision, accuracy and LOQ. 
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The method is considered acceptable for enforcement purposes in terms of materials, equipment,

and analysis time, for all crop matrices except dry crop matrices.

Conclusions. 

The FDA multi-residue protocols are not suitable for the analysis of oxathiapiprolin and 

associated metabolites. Depending on the crop matrix, HED notes that the QuEChERS and/or 

DFG Method S19 multi-residue methods may be suitable for the analysis of these compounds 

based on extraction solvents and clean-up strategies being similar to the analytical method 

described above. The QuEChERS and DFG Method S19 multi-residue methods were found to 

be unsuitable for the analysis of oxathiapiprolin and associated metabolites in dry crop matrices 

and high oil crop matrices, respectively. 

5.1.3 Tolerance Enforcement Methods

MRID No. 49011145 (Livestock)

Plant Commodities: The enforcement method is the same as the data collection method 

described in Section 5.1.1.

Livestock Commodities: A method titled “Analytical method for the determination of DPXQGU42 and metabolites in livestock tissues, milk and eggs using LC/MS/MS” (Report No: 

DuPont-31138) was submitted as an enforcement method for residues of oxathiapiprolin and 

associated metabolites in livestock commodities. The method is similar to that used for plant 

commodities, but with modifications depending on the matrix and analyte.

Residues of oxathiapiprolin and metabolites IN-RAB06, IN-RLB67, IN-RDG40 and IN-Q7H09 

are extracted from livestock tissue, milk and egg samples in acetonitrile and hexane using a 

Genogrinder extractor. The extracts are diluted with an aqueous formic acid solution and 

methanol. The analytes are determined via LC-MS/MS.

Method validation results showed that mean recoveries for residues of oxathiapiprolin and 

metabolites IN-RAB06, IN-RLB67, IN-RDG40 and IN-Q7H09 in whole eggs, whole milk, 

heavy cream, beef fat, beef muscle, beef kidney and beef liver were 82-119% at fortification 

levels of 0.01 and 0.10 ppm.

The method underwent an ILV. Mean ILV recoveries were 91-119% for residues of 

oxathiapiprolin, IN-RAB06, IN-RLB67, IN-RDG40, and IN-Q7H09 in whole eggs, whole milk, 

beef muscle and liver at fortification levels of 0.01 and 0.10 ppm, except in liver for IN-RDG40 

at fortification level of 0.01 ppm (mean recovery of 124%). As a result of the ILV 

investigations, a change to the HPLC conditions was recommended for the determination of INRDG40 in bovine liver and poultry eggs due to interference levels, and determination using the 

secondary ion transition was recommended for IN-RLB67 and IN-RDG40 in bovine liver.

The residue analytical method uses the same solvents (acetonitrile and hexane) as the goat and 

hen metabolism studies. The only difference is that the metabolism extraction protocol used a 

homogenizing probe while in the analytical residue method extraction, samples are extracted 
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using a Genogrinder. Since the extraction protocols are similar, it can be concluded that Method 

DuPont-31138 provides acceptable extraction efficiency.

In order to ensure unambiguous identification, two mass transitions for each analyte were 

monitored. Quantitation was performed using the mass transition 568→524 for IN-RAB06;

572→554 for IN-RLB67; 556→174 for IN-RDG40; 556→155 for IN-Q7H09; and 540→163 for 

oxathiapiprolin. Confirmation was performed using the mass transition 568→135 for INRAB06; 572→163 for IN-RLB67; 556→163 for IN-RDG40; 556→538 for IN-Q7H09; and

540→500 for oxathiapiprolin.

The method LOQ is 0.01 ppm for each analyte. The analytical method DuPont-31138 is 

considered suitable for enforcement purposes of oxathiapiprolin and metabolites IN-RAB06, INRLB67, IN-RDG40, and IN-Q7H09 in livestock matrices.

Conclusions.

The analytical methods for enforcement are adequate in terms of the tolerance expression and 

have passed both independent laboratory and Agency validation. 

5.1.4 Submittal of Analytical Reference Standards (860.1650)

A supply of oxathiapiprolin analytical standard is available in the National Pesticides Standards 

Repository. The standard has an expiration date of 04 June 2018. As a 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 CFR. The repository address is listed below and 

shipment should be sent to the attention of either Theresa Cole or Thuy Nguyen. Note that the 

full 9-digit ZIP code is mandatory or the mail will be returned to the sender. 

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

5.2 Storage Stability (860.1380)

MRID No. 49011204

The storage stability study on wheat forage, tomato, potato tuber, wheat grain, grape, dry bean 

seed, soybean seed, grape dry pomace, and wheat straw is considered to be scientifically

acceptable. Normalized recoveries showed that residues of oxathiapiprolin and metabolites INQ7H09, IN-RDG40, IN-E8S72, IN-RZB20, IN-RZD74, IN-SXS67, and IN-WR791 are stable 

for up to 18 months in crop matrices stored at or below -20°C. Samples were analyzed at various 

time points throughout the course of the storage period, including a 0-day time point for the RAC 

samples. Since the results of the study suggest that oxathiapiprolin and all seven metabolites 

investigated are stable in crop matrices with high water, high starch, high protein, high oil, and 

high acid content, stability is assumed for all crop commodities, including processed fractions, 

for up to 18 months when samples are stored frozen. Almost all recovery values were within the 
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acceptable range of 70-120%; only 11 individual samples had recoveries outside the acceptable 

range at 121-135%. The normalized recoveries for oxathiapiprolin and metabolites IN-Q7H09, 

IN-RDG40, IN-E8S72, IN-RZB20, IN-RZD74, IN-SXS67, and IN-WR791 in crop samples 

stored frozen at -20±10°C for up to 18 months ranged from 73 to 120%, demonstrating stability 

of residues in plant matrices under the given conditions. 

For a detailed summary of the concurrent recoveries of oxathiapiprolin and the associated seven 

metabolites, please see Appendix H. 

In the submitted livestock metabolism studies, samples were generally stored for six months or 

less prior to analysis; therefore, additional storage stability data are not required to support these 

data. 

Conclusions.

The submitted storage stability data are adequate to support the metabolism, field trials, and 

processing studies. The data demonstrate that residues of oxathiapiprolin and all seven 

metabolites investigated are stable in crop matrices with high water, high starch, high protein, 

high oil and high acid content, including processed fractions, for up to 18 months when samples 

are stored frozen. The seven metabolites included in the storage stability study are IN-Q7H09, 

IN-RDG40, IN-E8S72, IN-RZB20, IN-RZD74, IN-SXS67, and IN-WR791. 

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)

See Appendix K for a listing of MRID references for each Crop Field Trial Study.

Supervised residue trials with oxathiapiprolin were conducted in the U.S. and Canada with 

ginseng, tuberous and corm vegetables (potato), bulb vegetables (green onion and dry bulb 

onion), fruiting vegetables (tomato and pepper), leafy greens (lettuce and spinach), head and 

stem Brassica vegetables (broccoli, cauliflower, and cabbage), succulent peas (shelled seed and 

edible-podded), cucurbits (cantaloupe, summer squash, and cucumber), and tobacco. Adequate 

data were submitted to support the proposed greenhouse uses on tomato, pepper, and edible-peel 

cucurbits. For leafy greens, adequate data were submitted on representative crops, including 

head lettuce and leaf lettuce, as well as spinach. In support of the proposed tolerance on 

imported grapes, adequate trials were also conducted in the EU. The number of field trials are 

adequate based on the North American Free Trade Agreement (NAFTA) Guidance Document on 

Data Requirements for Tolerances on Imported Commodities in the United States and Canada

(December 2005). According to the guidance, twelve trials to support imported grape would be 

acceptable and data from eighteen trials are available. 

All matrices were assayed for residues of oxathiapiprolin and associated metabolites according to the data 

collection method described in Section 5.1.1. In the NAFTA field trials, with the exception of the EU 

grape and NAFTA potato study, all crop field trials tested for parent oxathiapiprolin and seven metabolites 

(IN-E8S72, IN-WR791, IN-RDG40, IN-Q7H09, IN-SXS67, IN-RZB20, and IN-RZD74). For the potato 
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field trials, oxathiapiprolin, IN-E8S72, and IN-WR791 were tested for, whereas the EU grape field trials 

tested for oxathiapiprolin, IN-E8S72, IN-WR791, IN-RDG40, and IN-Q7H09. 

The geographic distribution of the NAFTA field trials is summarized in Appendix I. Sufficient 

numbers of trials were conducted in geographically appropriate regions to support the 

establishment of tolerances in the proposed commodities.

With the exception of potato and summer squash, parent oxathiapiprolin was the predominant 

residue across all crop field trials. The field trials were generally conducted in a manner that was 

consistent with the proposed use pattern, both in terms of the proposed PHI and application 

rates/methods. Please see Table 5.3.1.2 for the GAP proposed use rates and PHI. For the same 

crop, field trials conducted using a foliar application method had generally higher residues than 

those conducted using direct soil application methods. Of the seven metabolites that were tested 

for, four metabolites were not detected above the LOQ in any of the field trials at the proposed 

PHI: IN-Q7H09, IN-RDG40, IN-RZB20, and IN-SXS67. At the proposed PHI, the remaining 

three metabolites (IN-E8S72, IN-RZD74, and IN-WR791) were relatively rarely observed in the 

field trials above the LOQ and generally at low levels compared to parent. At the proposed PHI, 

IN-E8S72 and IN-WR791 were quantifiable in ginseng, grape vine leaves, tobacco, and summer 

squash. IN-E8S72 was also at trace levels (≤ LOQ) in tomato; IN-WR791 was also quantifiable 

in succulent pea and non-bell pepper (up to 0.013 ppm); and IN-RZD74 was only quantifiable in 

tobacco matrices.

In the case of summer squash, metabolite IN-E8S72 was observed at slightly higher levels than 

oxathiapiprolin in the field trials conducted with only soil application methods (maximum INE8S72 residue of 0.021 ppm vs. oxathiapiprolin residue of 0.015 ppm). In the case of potato, no 

quantifiable residues were observed for oxathiapiprolin or any of the metabolites at the proposed 

PHI or at any other PHI assessed. As noted previously, for the potato field trials only

oxathiapiprolin, IN-E8S72, and IN-WR791 were tested for, whereas the EU grape field trials 

tested for only oxathiapiprolin, IN-WR791, IN-RDG40, IN-E8S72, and IN-Q7H09. 

Table 5.3.1.2 summarizes the North America crop field trial data at the GAP proposed PHIs, as 

well as the EU grape field trial data. Given that the residue of concern in primary crops has been 

defined as oxathiapiprolin only (see Section 4.3 for further details), Table 5.3.1.2. only captures 

the oxathiapiprolin residues. The registrant also submitted EU crop field trial data for the other 

EU proposed uses (see Table 3.3 for proposed EU use pattern; detailed field trial results not 

summarized here). Specifically, additional EU trials were conducted with edible and inedible 

peel cucurbits, tomatoes, lettuce, and potato. This EU crop field trial data is consistent with 

North American crop field trial data, with parent oxathiapiprolin being the predominant residue 

across the dataset. Metabolites were only rarely detected above the LOQ in any of the EU field 

trials. 

In the case of Crop Group 8-10, Fruiting Vegetables, the registrant has proposed excluding a 

tomato field trial (Trial 18) from the summary statistics and tolerance calculation. The registrant 

has provided a rationale for excluding this trial. Specifically, they indicate that the results from 

this trial “do not agree with the current body of knowledge for this active ingredient based both 

on physical-chemical properties and supervised field residue tests in multiple crops. In 
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particular, the following anomalies were observed: Oxathiapiprolin residues in tomato fruit were 

much higher at this trial following foliar application than at any other tomato or pepper 

supervised residue trial. Oxathiapiprolin residue in tomato fruit were higher at this trial than in 

the three tomato processing trials where oxathiapiprolin was applied at exaggerated rates. 

Oxathiapiprolin residues in tomato fruit were equally high following late-season soil applications 

as following late-season foliar applications. Oxathiapiprolin residues in tomato fruit were near 

0.1 mg/kg following early-season soil applications.” The tomato field trial HAFT from foliar 

application is 0.14 ppm if one excludes this trial and 0.31 ppm if one includes this trial. While 

HED agrees that the results from this trial do not appear to be consistent with the results of the

rest of the fruiting vegetable trials, the registrant has not provided sufficient evidence to exclude 

the trial (e.g., evidence that an error occurred in conducting the trial, such as misapplication of 

the fungicide at exaggerated non-GAP use rates, or that irregular weather conditions occurred 

that resulted in these residues). Therefore, HED has decided not to exclude this trial from the 

tomato field trial dataset. 

In the case of grape, ten EU trials conducted in 2010 and 2011 used a PHI of 9-11 days, whereas 

the proposed PHI is 14 days. However, eight additional trials were conducted in 2013 with a 

PHI of 14-15 days. The use rates in the grape trials were also slightly lower than the proposed 

use rate (0.8x-0.9x of GAP rate for 60% of the total submitted trials, with the remaining 40% 

conducted at ~1x). Overall, the 2010 and 2011 residue data is similar to that of the 2013 trials, 

with the combined dataset being considered adequate to support the proposed tolerance without a 

US registration. 

In the case of ginseng, the registrant submitted four field trials at the GAP proposed use rate and 

two field trials at ~2X the GAP. The registrant indicated that this was done because ginseng is a 

multi-year crop, often being harvested only after multiple growing seasons. At the two trials

where a 2X rate was used, side-by-side plots were established with one plot receiving the 

maximum application allowed for one season and a second plot receiving simulated multiple 

season applications. The multiple season scenario involved the maximum applications of 

oxathiapiprolin allowed for one season followed 45 days later by the maximum applications of 

oxathiapiprolin allowed for a second season. The resulting residues were exaggerated since there 

was only a 45-day window between “growing seasons” as compared to an 11-month separation 

of applications under realistic use. The oxathiapiprolin residues following the simulated multiseason treatment averaged 2X the oxathiapiprolin residues following the maximum single-season 

GAP treatment. The residue results from both approaches (GAP and 2X) are listed in Table 

5.3.1.2. For tolerance derivation purposes, the registrant has proposed using the residue data 

from the 2X trials and proportionally adjusting the residue data from the 1X trials (where sideby-side treatment was not undertaken) to be 2 times higher. Please see Section 6.0 for HED’s 

conclusions regarding this registrant proposal. Overall, HED concludes that there is sufficient 

ginseng field trial data to support the proposed use. 

Conclusions. 

The crop field trials are adequate for regulatory purposes, including for setting tolerances. For 

the NAFTA proposed uses, the number of trials is sufficient and the geographic distribution of 

the trials captures the major growing regions in the U.S., per OCSPP Series 860 Guidelines. 
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Adequate data is available to support the proposed greenhouse uses on tomato, peppers, and 

edible-peel cucurbits. While residue data was submitted on tobacco (and is summarized in Table 

5.3.1.2), as tobacco is a non-food use, no tolerance is recommended for tobacco. The submitted 

grape field trial data is also sufficient to support the proposed tolerance without a US registration

based on a proposed EU use. Data from the trials are representative of worst-case residues 

expected to result from application of oxathiapiprolin according to the proposed use patterns, and 

the residue data are supported by adequate analytical method performance and storage stability

data.
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Table 5.3.1.2. Summary of Oxathiapiprolin Field Trial Residue Data under GAP Proposed Conditions

Commodity

EPa

(Application Method)

Total 

Application 

Rate

lb ai/A

(g ai/ha)

DALA/ PHI 

(days)

Residue Levels in ppm (mg/kg)

n

b Min.b Max.b LAFTb HAFTb

Medianb

(STMdR)

Meanb

(STMR) Std. Dev.b

Crop Subgroup 1C, Tuberous and Corm Vegetables

(Proposed GAP: PHI = 5 days; Foliar application only; 0.178 lb ai/A maximum total application rate)

Potato Tubers 100 g/L OD

(Foliar) 

0.125–0.195

(140–219)

4–5 22 <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA

Grape (Import Tolerance Use Only Based on EU use pattern)

(Proposed GAP: PHI = 14 days; Foliar application only; 0.107 lb ai/A maximum total application rate)

Grape 

(Berries)

NEU and 

SEU

100 g/L OD

(Foliar)

0.087-0.112

(97.51-125.09) 9-15 18 0.021 0.41 0.021 0.41 0.12 0.15 0.123

Crop Subgroup 3-07A, Bulb Onion

(Proposed GAP: PHI = 0 days; Foliar application only; 0.125 lb ai/A maximum total application rate)

Dry Bulb 

Onion

100 g/L OD

(Foliar)

0.12-0.13

(134.94–

145.72)

0 12 <0.01 0.026 0.01 0.026 0.011 0.014 0.005

Crop Subgroup 3-07B, Green Onion

(Proposed GAP: PHI = 0 days; Foliar application only; 0.125 lb ai/A maximum total application rate)

Whole Plant 

Green Onion

100 g/L OD

(Foliar)

0.122-0.133

(137.81–

149.5)

0 5 0.38 0.86 0.40 0.85 0.57 0.58 0.18

Peas, succulent

(Proposed GAP: PHI = 0 days; Foliar application only; 0.125 lb ai/A maximum total application rate)

Shelled Seed 100 g/L OD

(Foliar)

0.125-0.137 

(140–153) 0 6 <0.01 0.029 <0.01 0.026 0.011 0.016 0.008
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Table 5.3.1.2. Summary of Oxathiapiprolin Field Trial Residue Data under GAP Proposed Conditions

Commodity

EPa

(Application Method)

Total 

Application 

Rate

lb ai/A

(g ai/ha)

DALA/ PHI 

(days)

Residue Levels in ppm (mg/kg)

n

b Min.b Max.b LAFTb HAFTb

Medianb

(STMdR)

Meanb

(STMR) Std. Dev.b

Whole Pea 100 g/L OD

(Foliar)

0.127-0.137 

(142–153) 0 6 0.20 0.55 0.20 0.55 0.29 0.315 0.121

Ginseng

(Proposed GAP: PHI = 14 days; Foliar application only; 0.50 lb ai/A maximum total application rate)

Ginseng, 

Dried Roots

100 g/L OD

(Foliar)

0.49-0.51

[548–571]

13–14 4 0.025 0.058 0.041 0.049 0.044 0.044 0.003

0.98-1.00

[1102–1125]

13–14 2 0.064 0.15 0.072 0.14 NA NA NA

Crop Subgroup 5A, Head and Stem Brassica Vegetables

(Proposed GAP: PHI = 0 days; Foliar application only; 0.125 lb ai/A maximum total application rate)

Broccoli 

Head

100 g/L OD 

(Foliar)

0.124-0.127

(139–142) 0 5 0.056 0.84 0.066 0.81 0.21 0.297 0.294

Cauliflower 

Head

100 g/L OD 

(Foliar)

0.124-0.128

(139–143) 0 5 0.073 0.17 0.077 0.14 0.082 0.094 0.026

Cabbage 

Head

100 g/L OD

(Foliar) 

0.122-0.128

(137–143) 0 10 0.043 0.46 0.044 0.42 0.14 0.178 0.129

Crop Subgroup 4A, Leafy Greens

(Proposed Gap: PHI = 0 days; Foliar application = 0.125 lb ai/A maximum application rate; Soil application = 0.50 lb ai/A maximum application rate)

Spinach 

Leaves

100 g/L OD

(Foliar)

0.122–0.129

(136.4–144.7) 0 10 1.3 7.0 1.4 6.5 3.4 3.7 1.9

Spinach 

Leaves

200 g/L SC

(Direct Soil)

0.490–0.513

(549.4–575.4) 0 10 <0.01 2.1 <0.01 2.1 0.11 0.75 0.92

Head Lettuce 

with Wrapper 

Leaves

100 g/L OD

(Foliar)

0.125–0.133

(140–149) 0 11 0.20 1.5 0.23 1.4 0.57 0.66 0.40
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Table 5.3.1.2. Summary of Oxathiapiprolin Field Trial Residue Data under GAP Proposed Conditions

Commodity

EPa

(Application Method)

Total 

Application 

Rate

lb ai/A

(g ai/ha)

DALA/ PHI 

(days)

Residue Levels in ppm (mg/kg)

n

b Min.b Max.b LAFTb HAFTb

Medianb

(STMdR)

Meanb

(STMR) Std. Dev.b

Head Lettuce 

with Wrapper 

Leaves

200 g/L SC /

100 g/L OD

(Direct Soil)

0.499–0.515

(560–578) 0 11 <0.01 0.47 <0.01 0.43 0.010 0.081 0.16

Leaf Lettuce 

Plant without 

Roots

100 g/L OD

(Foliar)

0.125–0.132

(140–148) 0 11 0.41 3.1 0.53 3.0 1.8 1.5 0.78

Leaf Lettuce 

Plant without 

Roots

200 g/L SC /

100 g/L OD

(Direct Soil)

0.486–0.515

(545–578) 0 11 <0.01 0.38 0.01 0.37 0.01 0.057 0.11

Leaf Lettuce

200 g/L SC

(Soil application - infurrow/drip/drench/shank/basal 

in-season)

0.491-0.499

(556-560) 0 3 <0.01 3.7 <0.01 2.9 0.01 1.0 1.7

Crop Group 8-10, Fruiting Vegetables

(Proposed Gap: PHI = 0 days; Foliar application = 0.125 lb ai/A maximum application rate; Soil application = 0.50 lb ai/A maximum application rate)

Tomato fruit 

– field and 

greenhousegrown c

100 g/L OD

(Foliar)

0.122-0.131

(136.3–146.8) 0 23 <0.01 0.35 <0.01 0.31 0.035 0.057 0.065

Tomato fruit 

– field grown 

c

200 g/L SC

(Direct Soil)

0.49-0.55

(553.8–610.9) 0 18 <0.01 0.44 <0.01 0.24 0.010 0.010 0.010

Tomato fruit 

– field grown

200 g/L SC

(Soil application - infurrow/drip/drench/shank/basal 

in-season)

0.499-0.504

(560-566) 0 3 <0.01 0.070 <0.01 0.054 0.010 0.025 0.025
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Table 5.3.1.2. Summary of Oxathiapiprolin Field Trial Residue Data under GAP Proposed Conditions

Commodity

EPa

(Application Method)

Total 

Application 

Rate

lb ai/A

(g ai/ha)

DALA/ PHI 

(days)

Residue Levels in ppm (mg/kg)

n

b Min.b Max.b LAFTb HAFTb

Medianb

(STMdR)

Meanb

(STMR) Std. Dev.b

Bell Pepper

Whole Fruit 

Field-grown 

and 

greenhouse

100 g/L OD

(Foliar)

0.123-0.132

(138-147) 0 12 0.013 0.14 0.016 0.12 0.032 0.045 0.037

Bell Pepper

Whole Fruit 

Field-grown 

200 g/L SC /

100 g/L OD

(Direct Soil)

0.498-0.593

(558-665) 0 10 <0.01 0.019 <0.01 0.017 0.010 0.011 0.002

Non-Bell 

Pepper

Whole Fruit

Field-grown

100 g/L OD

(Foliar)

0.125-0.139

(140-156) 0 6 0.019 0.13 0.028 0.12 0.057 0.063 0.035

Non-Bell 

Pepper

Whole Fruit

Field-grown

200 g/L SC /

100 g/L OD

(Direct Soil)

0.49-0.51

(546-568) 0 6 <0.01 <0.01 <0.01 <0.01 0.01 0.01 NA

Crop Group 9, Cucurbit Vegetables

(Proposed Gap: PHI = 0 days; Foliar application = 0.125 lb ai/A maximum application rate; Soil application = 0.50 lb ai/A maximum application rate)

Cantaloupe, 

Whole Fruit

100 g/L OD

(Foliar)

0.123-0.130

(138–146) 0 12 0.012 0.13 0.014 0.12 0.045 0.054 0.033

Cantaloupe,

Whole Fruit

200 SC/

100 OD

(Direct Soil)

0.50-0.52

(558–578) 0 12 <0.01 0.034 0.01 0.024 0.01 0.012 0.004

Cucumber 

Fruit, Field 

and 

Greenhouse 

Grown

100 g/L OD

(Foliar)

0.121-0.127

(136-142) 0 16 <0.01 0.096 <0.01 0.09 0.030 0.032 0.022
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Table 5.3.1.2. Summary of Oxathiapiprolin Field Trial Residue Data under GAP Proposed Conditions

Commodity

EPa

(Application Method)

Total 

Application 

Rate

lb ai/A

(g ai/ha)

DALA/ PHI 

(days)

Residue Levels in ppm (mg/kg)

n

b Min.b Max.b LAFTb HAFTb

Medianb

(STMdR)

Meanb

(STMR) Std. Dev.b

Cucumber 

Fruit,

Field-grown

200 SC / 

100 OD

(Direct Soil)

0.46-0.52

(518–578) 0 11 <0.01 <0.01 <0.01 <0.01 0.010 0.010 NA

Summer 

Squash

100 g/L OD

(Foliar)

0.123-0.133

(138–149) 0 10 <0.01 0.13 0.01 0.12 0.032 0.043 0.033

Summer 

Squash

200 g/L SC / 100 g/L OD

(Direct Soil)

0.50-0.52

(557–578) 0 10 <0.01 0.042 <0.01 0.026 0.010 0.012 0.005

Summer 

Squash

200 g/L SC

(Soil application - infurrow/drip/drench/shank/basal 

in-season)

0.499-0.504

(560-566) 0 3 <0.01 0.015 <0.01 0.013 0.010 0.011 0.0017

Tobacco, dried leaves 

(Proposed GAP: PHI = 7 days; Foliar application = 0.125 lb ai/A maximum application rate; Soil application = 0.50 lb ai/A maximum application rate)

Tobacco, 

Dried Leaves

100 g/L OD

(Foliar)

0.125-0.13

(140.0–145.4) 6-7 5 3.8 17 4.5 15 7.6 8.4 4.0

Tobacco, 

Dried Leaves

200 g/L SC

(Direct Soil)

0.50-0.51

(557.2–571.1) 7-42 5 <0.01 4.1 0.015 2.8 0.18 1.1 1.4

Note: For the computation of the median, mean, and standard deviation: values < LOQ are assumed to be at the LOQ (0.01 ppm). 

a EP = End-use Product 

b

n = Number of independent field trials; Min = Minimum individual specimen residue; Max = Maximum individual specimen residue; HAFT = Highest 

Average residue from one Field Trial; Median = Median based on per trial averages; Mean = Mean based on per trial averages; Std Dev = Standard 

deviation of mean. 

c

 Tomato crop field trial 18, with mean residues of 0.31 ppm (foliar trial) and 0.24 ppm (soil trial), was proposed as an outlier by the registrant. However, 

HED has concluded that this trial cannot be excluded and has therefore included this trial in the summary statistics. If Trial 18 were excluded, the tomato 

HAFT for foliar application is 0.14 ppm and for soil application is 0.028 ppm. 
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5.3.2 Field Rotational Crops (860.1900)

Two separate field rotational crop studies were conducted. The study design and summary of 

residue data results are provided below. Detailed tables of these residue data are available in 

Appendix C. 

Field Rotational Crop Study #1 (MRID 49011244) - Study Design

Application information:

Bare soil was treated with these targeted conditions:

Formulation: Oxathiapiprolin 100 g/L OD (DPX-QGU42-203)

Trt 2: 2 applications, 2 oz ai/A (57 g ai/A or 140 g ai/ha ; 0.125 lb ai/A) per application, 7-day retreatment interval.

Trt 3: 2 applications, 4 oz ai/A (113 g ai/A or 280 g ai/ha ; 0.25 lb ai/A) per application, 7-day retreatment interval.

No adjuvants were included for these soil applications.

No test substance was applied to untreated control plots (with the exception of Trial 01 60-day PBI wheat).

Prior to rotational crop planting, the plots were tilled. 

Three (rotational) crops were subsequently planted in the treated and untreated soil at the following targeted 

intervals after the last application (plantback intervals).

Rotational Crop Representation Raw Agricultural Commodities

Targeted Plantback 

Intervals (days)

Root vegetables Root crops tops, roots

7–30

60–120

300–365

Small grain cereals Cereal crops forage, hay, grain, straw

Soybean Legume vegetables forage, hay, immature seeds with 

pod, mature shelled seeds

Sampling information: 

For each targeted plantback interval, each rotational crop:

Treated plots: Duplicate samples of immature or commercially mature specified commodities.

Untreated control plots: Single samples of immature or commercially mature specified commodities.

Study #1 results - Residue analyses were conducted for parent plus metabolites IN-E8S72, INWR791, IN-RDG40, IN-Q7H09, IN-SXS67, IN-RZB20 and IN-RZD74. The residue data 

demonstrated the following:

 Average IN-Q7H09, IN-RDG40, IN-RZB20, IN-RZD74, and IN-WR791 residues are 

<LOQ (0.01 ppm) in all rotational crop commodities at all PBIs.

 With the exception of soybean forage (maximum residue of 0.033 ppm at the 560 g ai/ha 

seasonal rate), average oxathiapiprolin residues were <LOQ in all commodities. 

 Average IN-E8S72 residues in rotational crop commodities range from <LOQ in several 

commodities up to 0.16 ppm in soybean hay (at PBIs ranging from 7-30 days) at the 560 

g ai/ha rate (maximum seasonal rate).

 Average IN-SXS67 residues in rotational crop commodities range from <LOQ in several 

commodities up to 0.090 ppm in cereal grain hay (at PBIs ranging from 7-30 days) at the 

560 g ai/ha rate (maximum seasonal rate).
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Field Rotational Crop Study #2 (MRID 49011245) - Study Design

Application information:

Bare soil was treated with these targeted conditions:

Formulation: Oxathiapiprolin 100 g/L OD (DPX-QGU42-203) or 

Oxathiapiprolin 200 g/L SC (DPX-QGU42-213) (Trial 31 only)

Trt 2: 2 applications, 2 oz ai/A (57 g ai/A, 140 g ai/ha, 0.126 lb ai/A) per application, 7-day retreatment interval.

Adjuvants were included for these soil applications.

No test substance was applied to untreated control plots.

Prior to rotational crop planting, the plots were tilled.

Rotational crops were subsequently planted in the treated and untreated soil at the following targeted intervals after 

the last application (plantback intervals).

Rotational 

Crop

Crop 

Group Representation Raw Agricultural Commodities

Targeted 

Plantback 

Interval 

(days)

Sugar Beet 2

Leaves of Root and Tuber 

Vegetables Tops

5-10

Lettuce 4A Leafy Vegetables (except 

Brassica)

Immature leaves, leaves

Celery 4B Petioles (stalk)

Mustard 

Greens 5B Brassica Leaves

Soybean 6, 7 Legumes R6 Immature pod, 

R6 Immature seed, forage, hay, seed

Corn, Sweet

15, 16 Cereal Grains, Forage, 

Fodder, and Straw

Forage, ears (kernels plus cob with 

husks removed), stover

Corn, Field Forage, ears (immature grain plus cob 

with husks removed), stover

Sorghum Forage, stover

Wheat Forage, hay, straw

Canola 20A Oilseed Seed

Strawberry 13-07G Berries and Small Fruit Berries

Sampling information: 

For each targeted plantback interval, each rotational crop had:

Treated plots: duplicate samples of immature or commercially mature specified commodities.

Untreated control plots: single samples of immature or commercially mature specified commodities.

Study #2 Results - Residue analyses were conducted for parent plus metabolites IN-E8S72, INWR791, IN-RDG40, IN-Q7H09, IN-SXS67, IN-RZB20 and IN-RZD74. The residue data 

demonstrated the following in rotational crops grown in fields previously treated with 

oxathiapiprolin following 2 applications of oxathiapiprolin at 140 g ai/ha (0.126 lb ai/A) for a 

seasonal application rate of 280 g ai/ha (0.251 lb ai/A; 0.5X the maximum seasonal use rate):

 Average oxathiapiprolin, IN-Q7H09, IN-RDG40, IN-RZB20, and IN-RZD74 residues are 

<0.010 ppm in all rotational crop commodities at all PBI.

 Average IN-WR791 residues are 0.012 ppm in all rotational crop commodities.

 Average IN-E8S72 and IN-SXS67 residues in rotational crop commodities range from 

ND (<0.003 ppm) in several commodities up to 0.30 ppm in wheat hay at a 5-9 day PBI.
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Proposed Plant Back Interval Restrictions (Directly from the Proposed Labels)

Crop, Crop Group, or Crop Subgroup*

Plantback 

Restriction (in Days) 

following Last 

Application

Root and Tuber Vegetables (Group 1) 0

Bulb Vegetables (Group 3-07) 0

Leafy vegetables (Group 4) 0

Brassica Vegetables (Group 5) 0

Peas, succulent 0

Fruiting Vegetables (Group 8-10) 0

Cucurbit Vegetables (Group 9) 0

Strawberries 0

Herbs and Spices (Group 19) 0

Oilseed (Group 20) 0

Ginseng 0

Tobacco 30

Cereals (Group 15, 16) 30

Grass animal feeds (Group 17) 180

Legume Vegetables except succulent peas (Group 6) 180

Non-grass Animal feed (Group 18) 180

Peanuts 180

All other crops not listed 180

*Crop, Crop Group, or Crop Subgroup is given as listed on the proposed labels. 

Conclusions. Based on the residue definition for rotational crops being defined as parent 

oxathiapiprolin only, the submitted field rotational crop study data is adequate and the PBIs 

listed on the proposed labels are considered sufficient. Due to the lack of toxicity from 

oxathiapiprolin, USEPA would normally grant a tolerance exemption for this chemical. 

However, given that this chemical is being assessed as part of a global joint review and is 

intended to be registered in additional countries, the Agency is setting tolerances for 

harmonization purposes. Given that tolerances are being set solely for the purposes of 

harmonization with global partners, HED has concluded that it is appropriate to align the residue 

of concern for tolerance enforcement with the global partners. PMRA has set the residue of 

concern as parent oxathiapiprolin only in rotational crops and will be setting a generic action 

MRL of 0.10 ppm on all crops not currently proposed on the label. This generic action MRL of 

0.10 ppm will be used to provide coverage for inadvertent residues in rotational crops. HED 

concludes that this approach is adequate for the purposes of tolerance enforcement in rotational 

crops and that this aligned approach will avoid future trade irritants with global partners. 

5.3.3 Processed Food and Feed (860.1520)

MRID 49011237 Grape

MRID 49011238 Potato
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MRID 49011239 Tomato

Processing studies in grape, potato, and tomato were submitted with the petition. 

Grape

In the submitted grape processing study, four separate field trials were conducted, with two in 

Northern EU (NEU) and two in Southern EU (SEU). Three trials were conducted at ~1.2X the 

proposed maximum seasonal use rate, whereas the fourth trial was conducted at ~4.5X the 

proposed maximum seasonal use rate. Samples were assayed for residues of oxathiapiprolin and 

associated metabolites according to the method described in Section 5.1.1, and the residue results 

are supported by adequate storage stability data. Overall, consistent residue behavior was found 

in these NEU and SEU trials, providing data appropriate for assessing residues and processing 

factors through processing (Appendix J). It is noted that the GAP proposed PHI is 14 days, 

whereas these processing field trials were conducted at a 19-21 day PHI. Despite this mismatch, 

these data are considered adequate for the purpose of evaluating the concentration of residues in 

grape processed commodities. 

Each processed grape commodity (wine, juice, and raisin) showed a predictable residue profile 

consistent with the physical-chemical properties of oxathiapiprolin and with the loss of water to 

produce some commodities. Oxathiapiprolin residues concentrated in raisins (average 

processing factor of 2) relative to the raw fruit and reduced in juice, red wine, and white wine 

relative to the raw fruit, with average processing factors of 0.17, 0.14, and 0.13, respectively

(Appendix J). 

Grape Conclusions. 

The submitted grape processing study data is adequate for assessing the concentration of residues 

in processed commodities. Based on the above results, oxathiapiprolin residues are not expected 

to concentrate in grape juice or wine. Residues of oxathiapiprolin may concentrate in raisin. A 

tolerance value of 0.62 ppm (i.e., 0.41 ppm (HAFT) x 1.5 (median PF) = 0.62 ppm) is calculated 

for raisin. However, as this value is less than the recommended tolerance for grape (0.70 ppm), 

HED does not recommend in favor of a tolerance for raisin. 

Potato

The target study design for the submitted potato processing study included at-plant and midseason applications at a very exaggerated rate (1400 g ai/ha) in addition to exaggerated (175 g 

ai/ha) late-season foliar applications resulting in a total seasonal application of 3500 g ai/ha. 

After this processing study was conducted, the proposed GAP for potato was finalized with only

4 applications at 50 g ai/ha for a seasonal application of 200 g ai/ha (0.176 lb ai/A). Hence, the 

potatoes for processing were treated at an exaggerated rate of ~17.5 for the season. Three 

separate potato processing trials were conducted with this target study design, with the actual use 

rates resulting in exaggerated rates of 17.8-18.8x compared to GAP. Samples were assayed for 

residues of oxathiapiprolin and associated metabolites according to the method described in 

Section 5.1.1 and the residue results are supported by adequate storage stability data. 
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Overall, consistent residue behavior was found for applications conducted according to the 

specified exaggerated use pattern consisting of both soil and foliar applications. The data 

provided are adequate for assessing residues and processing factors through processing (see 

Appendix J for full details on deriving these processing factors). 

Processed potato commodities showed a predictable residue profile consistent with the physicalchemical properties of oxathiapiprolin and with the loss of water to produce some commodities. 

Oxathipiprolin concentrated in waste from the peeling processes (average/median processing 

factors of 1.6/1.1 and 1.4/0.4 for steam-peeling and abrasion-peeling, respectively), and being 

reduced or greatly reduced in all other commodities. Average processing factors ranged from 

<0.1 to 0.3 per commodity for washed tubers, culls, steam-peeled tubers, abrasion-peeled tubers, 

potato dried flakes, potato chips, peeled French fries, unpeeled French fries, boiled unpeeled 

potatoes, boiled peeled potatoes, and microwaved unpeeled (baked) potatoes. 

Potato Conclusions. 

The submitted potato processing study data is adequate for assessing the concentration of 

residues in processed commodities. In the 22 primary crop field trials for potato, which were 

conducted at the GAP proposed use rate and PHI, no quantifiable residues were observed in the 

potato RAC. If one multiples the median PF for potato waste from steam by the HAFT for the 

potato RAC (<0.01 ppm x 1.1), one would obtain 0.011 ppm. Given the lack of quantifiable 

residues in the primary crop potato field trial studies, this 0.011 ppm value for steam waste is 

conservative and likely an overestimate of residues in potato waste. Therefore, separate 

tolerances in processed potato commodities are not required. The potato RAC tolerance of 0.01 

ppm, which is being set at the tolerance enforcement method LOQ, should adequately cover 

processed potato commodities. 

Tomato 

The submitted tomato processing study included three separate field trials. The use pattern for 

these trials combined the soil application rate per season (0.62 lb ai/A, equivalent to 1x) with 

foliar application rate per application (0.62 lbs ai/A, 1.25x), for an overall seasonal application 

rate equivalent to 2.25x. Samples were assayed for residues of oxathiapiprolin and associated 

metabolites according to the method described in Section 5.1.1, and the residue results are 

supported by adequate storage stability data. 

Oxathipiprolin residues concentrated in sun-dried tomatoes and wet tomato pomace (median

processing factors of 6.9 and 13, respectively), remained constant in paste (average processing 

factor of 1.0) and were reduced in puree, washed tomatoes, juice, and peeled and canned 

tomatoes, with average processing factors of 0.5, 0.5, 0.2, <0.04, and <0.03, respectively. Please 

see Appendix J for more details on the derivation of these processing factors. 

Tomato Conclusions. 

The submitted tomato processing study data is adequate for assessing the concentration of 

residues in processed commodities. Based on the above results, oxathiapiprolin is not expected 

to concentrate in tomato juice, paste, or puree – the commodities for which HED typically makes 

tolerance recommendations. Residues of oxathiapiprolin may concentrate in wet pomace and 
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sun-dried tomato. Based on the tomato HAFT oxathiapiprolin residue of 0.31 ppm, the 

anticipated residue of oxathiapiprolin is 4.0 ppm in wet pomace and 2.1 ppm in dried tomato. 

Although HED would not normally set tolerances in dried tomato, it is noted that the registrant 

has petitioned for a dried fruiting vegetable tolerance based on these results. For simplicity

purposes in tolerance setting, the anticipated residue in dried tomato of 2.1 ppm is rounded up to 

the HED-recommended value of 3.0 ppm, with this rounding to 3.0 ppm being consistent with 

OECD rounding guidelines. Based on a review of the data and current policy on setting 

tolerances on non-standard processed commodities (ChemSAC minutes 04/01/2015), HED 

concludes that setting a tolerance value of 3.0 ppm for dried tomato would be appropriate. 

Following the HED Processing Factor Focus Group (PFFG) Guidance Document (2014, in 

draft), this tolerance is recommended for harmonization. It is noted that the setting of this dried 

tomato tolerance is consistent with the approach used for other recent global joint reviews (P. 

Savoia, D422374, 01/15/2015). However, HED concludes that a crop group tolerance of 3.0

ppm for all dried fruiting vegetables is not appropriate, as our regulations do not currently permit 

setting a crop group processed commodity tolerance (ChemSAC minutes 04/01/2015). 

5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

As summarized in Table 5.3.4.1, maximum reasonable dietary burdens (MRDBs) were 

calculated by for cattle, poultry, and swine based on the proposed tolerances and use pattern. 

The estimated MRDBs are 0.260 ppm, 0.393 ppm, 0.100 ppm, and 0.100 ppm in dairy cattle, 

beef cattle, swine, and poultry, respectively. These MRDB calculations include an assumption 

of tolerance level residues of 0.10 ppm in rotational crops, as well as the sole livestock feed 

items from the primary crop uses (potato culls and potato process waste). Potato culls and potato 

process waste were assumed to be present at LOQ levels (0.01 ppm), which is a worst case 

scenario assumption. Overall, HED considers these MRDBs to be very conservative. 

TABLE 5.3.4.1 Calculation of Dietary Burdens of Oxathiapiprolin Residues to Livestock.

Feedstuff Type1 % Dry 

Matter2

% Diet2 Recommended 

Tolerance (ppm)

Dietary Contribution 

(ppm)3

Beef Cattle

Corn gluten feed CC 40 75 0.10 0.188

Corn gluten meal CC 40 5 0.10 0.013

Canola meal PC 88 5 0.10 0.006

Pineapple process residue R 25 10 0.10 0.040

Sorghum forage R 35 5 0.10 0.014

TOTAL BURDEN -- -- 100 -- 0.260

Dairy Cattle

Carrot culls CC 12 10 0.10 0.083

Sweet corn cannery waste CC 30 10 0.10 0.033

Corn gluten feed CC 40 25 0.10 0.063

Peanut meal PC 85 10 0.10 0.012

Lespedeza forage RR 22 40 0.10 0.182

Field pea vine RR 25 5 0.10 0.020

TOTAL BURDEN -- -- 100 -- 0.393

Swine

Barley grain CC 88 20 0.10 0.020

Rice grain CC 88 20 0.10 0.020

Sorghum grain CC 86 45 0.10 0.045
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TABLE 5.3.4.1 Calculation of Dietary Burdens of Oxathiapiprolin Residues to Livestock.

Feedstuff Type1 % Dry 

Matter2

% Diet2 Recommended 

Tolerance (ppm)

Dietary Contribution 

(ppm)3

Field pea seed PC 90 15 0.10 0.015

TOTAL BURDEN -- -- 100 -- 0.100

Poultry

Rye grain CC 88 35 0.10 0.035

Barley grain CC 88 40 0.10 0.040

Field pea seed PC 90 20 0.10 0.020

Soybean seed PC 89 5 0.10 0.005

TOTAL BURDEN -- -- 100 -- 0.100

1. R = Roughage; CC = Carbohydrate Concentrate; PC = Protein Concentrate. 

2. Revisions of Feedstuffs in Table 1 of OPPTS Test Guideline 860.1000 and Guidance on Constructing Maximum 

Reasonably Balanced Diets (MRBD).; ChemSAC memorandum; 30 June 2008. 

3. Contribution = ([tolerance ÷ %DM] x %diet) for beef and dairy cattle. Contribution = (tolerance x %diet) for 

poultry and swine.

Based on the low residues of oxathiapiprolin and all metabolites in the goat metabolism study, a 

cattle feeding study was not conducted. The majority of the administered dose (>85%) was 

eliminated in the excreta. Overall low residues of parent oxathiapiprolin and metabolites were 

observed in the other goat matrices, with a maximum residue of 0.129 ppm. Given that the goat 

metabolism study was conducted at ~36X the anticipated dietary burden in ruminants, there is no 

expectation of finite residues in ruminant commodities and no ruminant tolerances have been 

proposed. 

In the hen metabolism study, oxathiapiprolin and metabolites were readily eliminated in the 

excreta (including cage wash), where 95-100% of the dose was recovered. Overall the highest 

residue observed in the other hen matrices was 0.014 ppm in liver for unresolved oxathiapiprolin 

hydroxy metabolites. Parent oxathiapiprolin was the predominant residue across hen matrices. 

Given that the hen metabolism study was conducted at ~174 the anticipated dietary burden of the 

proposed uses, there is no expectation of finite residues for poultry matrices and no poultry

tolerances have been proposed at this time. 

Conclusions. At this time, based on the livestock metabolism studies and the anticipated 

livestock dietary burden, no detectable residues of oxathiapiprolin are expected in livestock 

commodities (category 6(a)3); therefore, there are no oxathiapiprolin-related residues expected 

in livestock commodities and HED concludes that tolerances for livestock commodities are 

unnecessary. 

If future uses of oxathiapiprolin are requested on crops which serve as significant livestock 

feedstuffs, livestock feeding studies may be required. 

5.3.5. Food Handling (860.1460)

At this time, there are no food-handling establishment uses associated with oxathiapiprolin.

5.3.6 Water, Fish, and Irrigated Crops (860.1400)
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At this time, there are no water, fish, or irrigated crop uses associated with oxathiapiprolin.

5.4 Food Residue Profile

The submitted residue chemistry studies were generally well conducted and are adequate for 

supporting regulatory conclusions, establishing appropriate tolerance levels for enforcement, and 

for purposes of risk assessment. Analysis of residues can be accomplished through standard 

analytical techniques, and residues do not show any trends for dissipation during frozen storage. 

With the exception of the potato field trials where no quantifiable oxathiapiprolin residues were 

observed, one or more field trials from all other primary crops had quantifiable oxathiapiprolin 

residues. These oxathiapiprolin residues were generally substantially higher than any of the 

seven metabolites listed above. The registrant also submitted a large amount of residue decline 

data which generally demonstrated that residues of oxathiapiprolin decrease with increasing PHI 

(results not presented here; see study specific MRID DERs for further details). All residue study 

results are supported by adequate storage stability data and these field trial studies were 

conducted using the proposed analytical enforcement method. 

Due to the lack of toxicity from oxathiapiprolin, USEPA would normally grant a tolerance 

exemption for this chemical. However, given that this chemical is being assessed as part of a 

global joint review and is intended to be registered in additional countries, the Agency is setting 

tolerances for harmonization purposes. Given that tolerances are being set solely for the 

purposes of harmonization with global partners, HED has concluded that it is appropriate to align 

the residue of concern for tolerance enforcement with the global partners. PMRA has set the 

residue of concern as parent oxathiapiprolin only in rotational crops and will be setting a generic 

action MRL of 0.10 ppm on all crops not currently proposed on the label. This generic action 

MRL of 0.10 ppm will be used to provide coverage for inadvertent residues in rotational crops. 

HED concludes that this approach is adequate for the purposes of tolerance enforcement in 

rotational crops and that this aligned approach will avoid future trade irritants with global 

partners. 

Also, if there are future uses on crops that are significant livestock feedstuffs, then livestock 

feeding studies may be necessary.

6.0 Tolerance Derivation

The recommended tolerance levels for RAC commodities were obtained using the OECD 

calculation procedures. With the exception of grape and ginseng, average residues of 

oxathiapiprolin from field trials conducted according to the proposed label were used in the 

calculations. Please see Table 5.3.1.2 for the GAP proposed use rates and PHI. 

For the crop group tolerance calculations (fruiting vegetables, cucurbit vegetables, leafy greens, 

and Brassica vegetables), within each crop group, the residue levels between the representative 

commodities did not vary by more than 5-fold, indicating that crop-group tolerances are 

appropriate. Residues from each representative commodity were used to get commodity-specific 

tolerance levels and the maximum commodity-specific tolerance within the crop group was 
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selected as the recommended tolerance for the entire group. The residue data and calculation 

procedure outputs for each representative commodity are included in Appendix M.

For the crop uses where both foliar and soil application methods are proposed (leafy greens, 

cucurbits, fruiting vegetables, tobacco), the proposed labels do not allow foliar and soil 

application methods to be used interchangeably within the same season. Therefore, it is not 

appropriate to merge the field trial results from foliar and soil application methods. The foliar 

application trials yielded higher residues than the soil application trials across commodities. 

Therefore, the tolerances were derived using the foliar trials and these tolerances are protective 

of the residues observed in the soil application method field trials. 

As discussed previously, in the case of grape, the EU trials conducted in 2010 and 2011 used a 

PHI of 9-11 days, whereas the proposed PHI is 14 days. For tolerance derivation purposes, these 

2010 and 2011 trials were combined with eight 2013 trials conducted at a PHI of 14-15 days. 

The 2010 and 2011 residue data is similar to that of the 2013 trials, with the combined dataset 

being considered adequate to support the proposed tolerance. Please see Table 5.3.1.2 for the 

GAP proposed use rates and PHI. 

The registrant also submitted EU crop field trial data for the other EU proposed uses (see Table 

3.3 for proposed EU use pattern; detailed field trial results not summarized here). Specifically, 

additional EU trials were conducted with edible and inedible peel cucurbits, tomatoes, lettuce, 

and potato. This EU crop field trial data is consistent with North American crop field trial data, 

with parent oxathiapiprolin being the predominant residue across the dataset and generally lower 

residues being observed in the EU field trial dataset. Only the NAFTA field trial data was used 

in the tolerance calculations, with this NAFTA data being protective of the residues observed in 

the EU studies. 

In the case of ginseng, the registrant submitted four field trials at the GAP proposed use rate and 

two field trials at ~2X the GAP. The registrant indicated that this was done because ginseng is a 

multi-year crop, often being harvested only after multiple growing seasons. Please see section 

5.3.1 for further details on these trials. For tolerance derivation purposes, the registrant has 

proposed using the residue data from the 2X trials and proportionally adjusting the residue data 

from the 1X trials (where side-by-side treatment was not undertaken) to be 2 times higher. 

Using the 2X trial data, a tolerance of 0.40 ppm is derived. However, based on a review of the 

data and consultation with the global partners, HED has concluded that using the 1X data is more 

appropriate for tolerance-setting, yielding a 0.15 ppm recommended tolerance. 

In the case of Crop Group 8-10, Fruiting Vegetables, the registrant proposed excluding a tomato 

field trial (Trial 18) from the tolerance calculation. If this trial is excluded, all representative 

commodities (bell pepper, non-bell pepper, and tomato) support a crop group tolerance of 0.20 

ppm. However, HED has decided not to exclude this trial from the tolerance derivation (see 

Section 5.3.1. for further details). With the inclusion of Trial 18, the recommended tomato 

tolerance becomes 0.50 ppm and, consequently, the recommended Fruiting Vegetable Crop 

Group 8-10 tolerance becomes 0.50 ppm. It is noted that if both small and standard tomato 

cultivars are included together in the tolerance calculations, the recommended tomato tolerance 

is 0.40 ppm (as presented in Appendix M). However, Canada’s PMRA has concluded that 
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tolerance calculations must be conducted separately for small and standard tomato cultivars. 

Using the 11 field trials for small tomato cultivars, they derived a 0.50 ppm tolerance. While

HED would not normally calculate a tomato tolerance in this manner, given that HED is setting 

tolerances solely for the purposes of harmonization with global partners, a value of 0.50 ppm is 

considered adequate. 

As discussed previously (see section 5.3.3), separate tolerances in processed potato and grape 

commodities are not required. Additionally, oxathiapiprolin is not expected to concentrate in 

tomato juice, paste, or puree – the commodities for which HED typically makes tolerance 

recommendations. Residues of oxathiapiprolin may concentrate in wet pomace and sun-dried 

tomato. Based on the tomato HAFT oxathiapiprolin residue of 0.31 ppm, the anticipated residue

of oxathiapiprolin is 2.1 ppm in dried tomato. Although HED would not normally set tolerances 

in dried tomato, it is noted that the registrant has petitioned for a dried fruiting vegetable 

tolerance based on these results. For simplicity purposes in tolerance setting, the anticipated 

residue in dried tomato of 2.1 ppm is rounded up to the HED-recommended value of 3.0 ppm, 

with this rounding to 3.0 ppm being consistent with OECD rounding guidelines (ChemSAC 

minutes 04/01/2015). Based on a review of the data and current policy on setting tolerances on 

non-standard processed commodities (ChemSAC minutes 04/01/2015), HED concludes that 

setting a tolerance value of 3.0 ppm for dried tomato would be appropriate. Following the HED 

Processing Factor Focus Group (PFFG) Guidance Document (2014, in draft), this tolerance is 

recommended for harmonization. It is also noted that the setting of this dried tomato tolerance is 

consistent with the approach used for other recent global joint reviews (P. Savoia, D422374, 

01/15/2015). However, HED concludes that a crop group tolerance of 3.0 ppm for all dried 

fruiting vegetables is not appropriate, as our regulations do not currently permit setting a crop 

group processed commodity tolerance (ChemSAC minutes 04/01/2015). 

7.0 ChemSAC Reference

This memorandum was reviewed by the Chemistry Science Advisory Council (ChemSAC) on 

April 1, 2015 and has been revised to reflect the recommendations of that group.