UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 05/19/201 5 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

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

Registration for Use on Pepper/Eggplant subgroup 8-108 and Wheat. Summary of 

Analytical Chemistry and Residue Data. 

PC Code: 128849 

Decision No.: 495311. 495616 

Petition No.: 4F83 I 5 

Risk Assessment Type: NA 

TXR No.: NA 

MRJD No.: See Below 

DP Barcode: 0427236 

Registration No.: I 0163-251 

Regulatory Action: Registration Review 

Case No.: 7404- 1 

CAS No.: 78587-05-0 

40 CFR: 40 CFR 180.448 

~i·,~~~~t~: ~~:·;:;~ ; 7509P) ~ ~ Through: Michael Metzger, Chief : , ( /) () /) OFrom: 

Co/vi /IS 

RAV VNII; HED (7509P) ,., i{_ ~ '/_ 

' 

To: Olga Odiott, Risk Manager 

Mark Suarez, Product Manager 

Meredith Laws, Chief 

Insecticide Branch 

Risk Management Division (Mail Stop) 

Summary of Submit1ed Residue Chemistry Studies 

OCSPP 860 MRID Series Number Re fe rence Title 

Guideline 

860.1000, Magnitude of the Residue of Hexythiazox in Wheat Aspirated 

860.1500 & 49472901 4947290 l .der.docx Grain Fractions And Processed Commodities Following One 

860. 1520 Foliar Aool ication of Onager® IE Miticide (20 I 3) 

Magnitude of the Residue of Hexythiazox in or on 

860.1000 & 49465401 4946540 I .der.docx Greenhouse Grown Bell Pepper Raw Agricultural 

860.1500 Commodities Following One Foliar Application ofOnager® 

IE or Hexygon® 50DF Miticide--2013 

Page l of 15 
Hexythiazox Summary of Analytical ChemistTy and Residue Data Barcode 0427236 

Table of Contents 

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

2.0 Regulatory Recommendations .... ................................................................................... ..... 3 

2. 1 Data Deficiencies/Data Needs .......................................................................................... 3 

2.2 Tolerance Considerations ................................................................... ....... ....................... 3 

2.2.1 Enforcement Analytical Method .................................................... .... ... .................... 3 

2.2.2 Recommended Tolerances ...... .... .... ....................................... ............................ ....... 3 

2.2.3 Revisions to Petitioned-For Tolerances .................. ................................ .... ... ....... ... . 4 

2.2.4 International Harmonization ..... ..... .... .................... ................................ .... ... ....... ..... 4 

3.0 Introduction ................................ .... ......................................................................... ............ 4 

3. 1 Che1nical Identity ........ ..................................................................................................... 5 

3.2 Physical/Chemical Characteristics ................................................................................... 5 

3.3 Pesticide Use Pattern/Directions for Use (860. 1200) ....................................................... 6 

4.0 Metabolite/Degradate Residue Profile ................................................................................ 6 

4.1 Nature of the Residue ....................................................................................................... 6 

4.1.1 Summary of Plant Metabolism (860.1300) .... ........................................... ....... ... ...... 6 

4.3 Residues of Concern Summary and Rationale ...................................... ........................... 7 

5.0 Residue Profile ..................................................................................... ....... .... .................... 7 

5.1 Residue Analytical Methods (860.1340) ........................................................ ....... ... ........ 7 

5. 1.1 Data Collection Methods ............................................................. ............................. 7 

5.1.3 Tolerance Enforcement Methods ....................................................... ....... ....... ......... 7 

5.3 Residue Data .................................................................................................................... 8 

5.3. 1 Crop Field Trials (860.1500) ..................................................... ....... .......... .............. 8 

5.3.3 Processed Food and Feed (860. 1520) ....................................................................... 9 

5.3.4. l Dietary Burden .................................................................. .............................. I 0 

5.3.4.2 Estimated Secondary Residues in Li vestock ......................................... .......... 11 

5.3.5. Food Handling (860.1460) ...................................................................................... 12 

5.3.6 Water, Fish, and Irrigated Crops (860.1400) .......................................................... 12 

6.0 Tolerance Derivation ................................................................................... ..................... 12 

Appendix 1. Field Trial Geographic Distribution ................................................................ ....... . 13 

Appendix 2. International Residue Limits Table ...................................................... ... .... ... .... ..... 14 

Appendix 3. OECD MRL Calculation Procedure Inputs/Outputs ........................ ....................... 15 

Page 2 of 15 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

1.0 Executive Summary 

The Onager® Miticide label will be amended to include the use of hexythiazox on wheat. The 

registrant (Gowan Company) has petitioned (PP# 1 F7934) for the Agency to establish a 

tolerance on wheat, alfalfa, and timothy. Data was submitted in support of the tolerance 

establishment however, a processing study was required to show if residues of hexythiazox 

concentrate in processed wheat commodities. The Gowan Company has submitted a wheat 

processing study that was required in order to establish a tolerance under 40 CFR 180.448 (c) for 

residues of hexythiazox on wheat; forage, hay, straw, and grain. 

Also, the Hexygon® Miticide label will permit the use of hexythiazox on pepper/eggplant 

subgroup 8-IOB. Gowan has submitted the magnitude of the residue study for hexythiazox on 

greenhouse grown bell peppers. 

2.0 Regulatory Recommendations 

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

registration and establishing the recommended tolerances for hexythiazox on wheat and 

pepper/eggplant subgroup 8-1 OB. The specific tolerance recommendations are discussed in 2.2, 

and label modifications are discussed in section 2.3. 

2.1 Data Deficiencies/Data Needs 

No data deficiencies have been discovered at this time. 

2.2 Tolerance Considerations 

2.2.1 Enforcement Analytical Method 

Hexythiazox and its metabolites are not consistently recovered through FDA's multi-residue 

methods. No data were provided, or are required, for recovery through other common multiresidue methodology. 

An adequate HP LC/UV analytical method is avai lable for the enforcement of tolerances for 

residues of hexythiazox and its metabolites containing the PT-1-3 moiety in crop and livestock 

commodities. This method is listed in the U.S. EPA Index of Residue Analytical Methods under 

hexythiazox as method AMR-985-87. The specifies of the method are detailed in Section 5.1.3 

of this memorandum. 

2.2.2 Recommended Tolerances 

Tolerances currently established under 40 CFR §I 80.448 comply with the HED Interim 

Guidance on Tolerance Expressions (S. Knizner, 5/27/09); therefore, no revisions are 

recommended to the residue definition. Table 2.2.2, below summarizes the recommended 

tolerance levels and commodity definitions required to support the proposed new and revised 

uses included in these petitions. 

Page 3of 15 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

Gowan Company has submitted a tolerance petition for hexythiazox on wheat forage, hay, grain, 

and straw in agreement with the HED recommended tolerances from the past residue chemistry 

review (D396862, D. Drew, 06/18/2012). Aspirated grain fractions (AGF) tolerance is 

established at 5.0 ppm which is greater than the HAFT (0.17 ppm) multiplied by the processing 

factor (8.5x) from the recently submitted processing study (494790 1.der.docx, K.King, 

04/14/2015). Tolerances were established for combined residues of hexythiazox and its 

metabolites containing the ( 4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety. 

Table 2.2.2. Tolerance Summary for Hexythiazox. 

Commodity Established/Proposed H EO-Recom mended Comments 

Tolerance (ppm) Tolerance (ppm) (correct commoditv definition) 

Wheat, Forage 6.0 6.0 Wheat, forage (EPA Zone 11 only)* 

Wheat, Hay 30 30 Wheat, hay (EPA Zone 11 only)* 

Wheat, Grain 0.02 0.02 Wheat, grain (EPA Zone 11 only) 

Wheat, Straw 8.0 8.0 Wheat, straw (EPA Zone 11 only)• 

AGF 5.0 -- Grain, aspirated fractions 

Pepper/Eggplant 8-1 OB 1.5 1.5 Peooer/E!?.!?.olant subgroup 8-1 OB 

*Recommended tolerance based on outcome ofOECD MRL calculation from 2012 memo 0396862. 

The Organization for Economic Cooperation and Development maximum residue limit (OECD 

MRL) was calculated for Onager® Miticide with the 2013 greenhouse bell pepper data as well as 

previously submitted bell pepper average field trial data with the same application rate 

(D404573& 4 10813, D. Davis, 05/02/2013). The calculated MRL is 0.5 ppm which is less than 

the established tolerance of 1.5 ppm from the 40 CFR § 180.448 for pepper/eggplant subgroup 8-

1 OB. The submitted field trials with Hexygon® Miticide applications showed values that were 

less than the calculated MRL and are not expected to exceed the established tolerance for 

pepper/eggplant subgroup 8-1 OB. 

2.2.3 Revisions to Petitioned-For Tolerances 

There are no differences from the petitioned-for-tolerances and the tolerances that are being 

recommended by HED. 

2.2.4 International Harmonization 

There are no established Codex MRLs for any crop group be applied with hexythiazox. 

2.3 Label Recommendations 

There are no labe l recommendations at this time. 

3.0 Introduction 

Hexythiazox, trans-5-( 4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxothiazol idine-3-

carboxamide, is an ovicide/miticide used to control mites on a variety of fruit and nut crops. 

Page 4 of 15 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

Hexythi azox is a contact pesticide which achieves control of eggs or immature mites via direct 

contact or contact with treated surfaces. 

The chemical structure and nomenclature of hexythiazox and its common moiety, PT-1 -3 is 

shown in Table 3. I. The physicochemical prope11ies of the technical grade hexythiazox are 

presented in Table 3.2. 

3.1 Chemical Identity 

Ta ble 3.1. Nome nclature of Hexythiazox. 

Compound 

N,,lND H3

C 

- Cl 

~ /; SAO H 

Common name Hexythiazox 

Company experimental names DPX-Y5893, NA-73 

IUPAC name ( 4RS,5RS)-5-( 4-chloropheny l)-N-cyclohexyl-4-methyl-2-oxo-1 ,3-thiazol id ine-3-

carboxamide 

CAS name trans-5-( 4-ch lorophenyl)-N-cyclohexy 1-4-methyl-2-oxo-3-

th iazol idinecarboxamide 

CAS # 78587-05-0 

End-use product/EP I lb/gal EC (EPA Reg. No. 10 163-277; Onager® Ovicide/Miticide) 

Compound H.C 

J H 

N 

( 4-ch lorophenyl)-4-methyl-2- f ~ SAO oxo-3-thiazolidine moiety Cl 

-

Common name PT- 1-3 moiety 

Chemical name 5-( 4-ch lorophenyl)-4-methyl-thiazol idin-2-one 

3.2 Physical/Chemical Cha racteristics 

Table 3.2. Physicochemica l Properties of Hcxythiazox 

Parameter Value Reference' 

Melting point/range (°C) I 08.0-108.5°C 00143533 

pH NIA 

Density (g/cm3) 1.289 at 25°C 00143533 

Water solubility 0.12 ppm 44006301 

Solvent solubility g/L 00143533 

chloroform 1379 

xylene 362 

acetone 160.0 

acetonitrile 28.6 

n-hexane 3.9 methanol 

Page 5of 15 
Hexythiazox Summary of Analytical Chemisrry and Residue Data Barcode 0427236 

Table 3.2. Physicochemical Properties of Hexythiazox 

Parameter Value Reference ' 

Vapor pressure 10·~ mm Hg at 25 °C 44006301 

Dissociation constanr (PKa) NIA 

Octanol/water partition coefficient Log(Kow) 560 (average) 0143533.00146531 

UV /visible absorption spectrum Maximum at 223 nm in NIA 

(molecular absorption coefficients) acetonitrile, no absorption in the 

visible range. 

1 References and values as cited in the petition materials for PP#9F7556 and PP#9F7549. 

3.3 Pesticide Use Pattern/Directions for Use (860.1200) 

Table 3.3. Summary of Proposed Directions for Use ofl-lexythiazox. 

Applic. Timing, Formulation Applic. Max. No. Max. Seasonal PHI Use Directions 

Type, and Equip. [EPA Reg. Rate Applic. per Applic. Rate (days) and Limitations No.] (lb ai/A) Season (lb ai/A) 

Wheat 

Use against 

Foliar by Ground Banks grass mite 

Application, Air Onager® IE on wheat, 

Miticide 20 I 20 14 including emmer Application, or [I 0163-277] wheat and Chemigalion triticale (West of 

the Rockies) 

Pepper/Eggplant Subgroup 8-1 OB 

Used against 

Tetranychid 

Mites, Pacific 

Foliar by Ground Hexygon® spider mite, and 

Strawberry Application. Air 50 OF 653.4 I 653.4 I spider mite on Application was Miticide subgroup 8-1 OB not specified [10163-251] (including 

greenhouse 

plants grown for 

transplant) 

Conclusions. 

Labels are adequate to allow evaluation of the residue data relative to the proposed use. No label 

changes are required at this time. 

4.0 Metabolite/Degradate Residue Profile 

4.1 Nature of the Residue 

4.1.1 Summary of Plant Metabolism (860.1300) 

Residue Chemistry Memo 0377982, 11/29/ 10, 0. Davis (PP#9F7549) 

The nature of the residue in plants has been adequately addressed and no additional data is 

required. 

Page 6of15 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode D427236 

4.1.2 Summary of Livestock Metabolism and Residues of Concern (860.1300) 

Residue Chemistry Memo D377982, 11 /29/10, D. Davis (PP#9F7549) 

Residue Chemistry Memo D396862. 6/ 18/ 12. D. Drew (PP# I F7934) 

The nature of the residue in livestock has been adequately addressed and no additional data is 

required. 

4.1.3 Summary of Confined Rotational Crops and Residues of Concern (860.1850) 

Residue Chemistry Memo DP# 360414, 08/ 17109, D. Davis (PP#7E7182) 

Residue Chemistry Memo DP# 347948, 02114/08, T. Bloem (PP#5F6953) 

Residue Chemistry Memo, DP#s 247631 and 260343, 0312012000, G. Kramer 

Residue Chemistry Memo, DP#s 404573 and 4108 13, 05102/2013, D. Davis (PP#2F8054 and 2E801 6) 

Additional confined rotational crop data are not required at this time. 

4.3 Residues of Concern Summary and Rationale 

Residue Chemistry Memo D377982, 11 /29110, D. Davis (PP#9F7549) 

Residue Chemistry Memo D396862, 6/ 18112, D. Drew (PP# l F7934) 

Table 4.3. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression 

Matrix Residues included in Risk 

Assessment 

Plants Primary Crop Hexythiazox and metabolites 

Rotational Crop Hexythiazox and metabolites 

Livestock 

Ruminant Hexythiazox and metabolites 

Poultry Hexythiazox and metabolites 

Drinking Water 

5.0 Residue Profile 

5.1 Residue Analytical Methods (860.1340) 

5.1.1 Data Collection Methods 

4879870 l.der, 4123113, D. Davis (pepper) 

Residues included in 

Tolerance Expression 

NIA 

NIA 

NIA 

NIA 

Not Applicable 

The residue analytical methods used to generate pepper field trial data have been adequately 

validated and are acceptable for data collection purposes. 

5.1.3 Tolerance Enforcement Methods 

An adequate HPLC/UV analytical method is available for the enforcement of tolerances for 

residues of hexythiazox and its metabolites containing the PT-1-3 moiety in crop and livestock 

Page 7of1 5 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

commodities. This method is listed in the U.S. EPA Index of Residue Analytical Methods under 

hexythiazox as method AMR-985-87. 

Briefly, residues are extracted three times with methanol (watery crops, livestock tissues, eggs. 

and milk) or methanol:water (80:20, v:v; low water-content crops) and centrifuged; for milk, 

NaCl is added to the first aliquot of methanol. For crop samples, except oily crops, the combined 

extracts arc concentrated, and combined with acidified water (pH 2) and dichloromethane 

(DCM); NaCl is added, and the phases are allowed to separate. The DCM phase is collected, and 

the extract is partitioned again with DCM. The DCM phases are combined and subjected to base 

hydrolysis with 0.1 N NaOH solution and NaCl to convert residues of hexythiazox and 

metabolites to PT-1-3. Following phase separation, the aqueous phase is partitioned with DCM, 

and the DCM phases are combined. For livestock commodities and oily crops, following initial 

partitioning with DCM as described above, the combined DCM phases are partitioned with 

hexane (2x), and the hexane phases are combined and partitioned with hexane-saturated 

acetonitrile (ACN; 2x). The resulting ACN phases are combined and concentrated at 60 °C, and 

0.1 N NaOH solution is added to the hot extract to convert residues to PT-1-3. After 30 minutes. 

water and NaCl are added, and the resulting aqueous solution is partitioned with DCM (2x), and 

the DCM phases are combined. The resulting DCM phases for all commodities are cleaned up 

by gel permeation chromatography (citrus only) and silica column chromatography. For silica 

column clean-up, the DCM phase is concentrated and partitioned with hexane (2x), and the 

resulting hexane phase is applied to the silica column; residues are eluted with ethyl 

acetate:hexane (20:80, v:v). The eluate is concentrated and adjusted to volume with ACN/water 

for HP LC/UV analysis. Residues are expressed in terms of hexythiazox using a molecular 

weight conversion factor of 1.55. The method LOQ is 0.02 ppm. 

Conclusions. Acceptable methodology is available for tolerance enforcement purposes for 

residues of concern in/on all the commodities that are the subject of this memorandum. 

5.3 Residue Data 

5.3.1 Crop Field Trials (860.1500) 

4946540 I .der.docx. 04/ 14/2015, K.King (pepper) 

Gowan Company submitted field trial data for hexythiazox on greenhouse grown bell peppers. 

Two side-by-side field trials were conducted in the United States during the 20 13 growing 

season in the North American Free Trade Agreement (NAFTA) growing regions 3 (FL) and I 0 

(CA). Table 5.3.1 shows the field trial uses and residues data for the two trials. Each trial 

Page 8of15 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

Table 5.3.1. Summar of Residues from Field Trials with Hexythiazox. 

App lie. Residues (ppm) 

Crop Analyte Rate PHI . Matrix (lb (days) n Min.t Max.t LAFT' HAFT' Median . Mean . so· ai/acre) 

Pepper/Eggplant, Subgroup 8- 1 OB, 0.1875 lbs ai/ A, I day PH I 

On ager® 

Bell Hexythi IE I 2 0.174 0.456 0. 192 0.437 0.3 14 0.3 14 0.173 Pepper azox Miticide 

(0.1875) 

Hexygon 

Bell Hexythi ® 50DF I 2 0.139 0.363 0.149 0.302 0.200 0.225 0.108 Pepper azox Miticide 

(0. 1875) 

t Values based on total number of samples. 

·Values based on per-trial averages. LAFT = Lowest /\verage Field Trial. HAFT = Highest Average Field Trial. SD = Standard 

Deviation. For computation of the LAFT. l lAFT. median. mean. and standard deviation. values< LOQ arc assumed to be at the 

LOQ. 

Conclusions 

The bell pepper field trials are considered scientifically acceptable. The results of the study 

showed that following a single application of 0.1875 lbs ai/ A with a 1 day PHI, hexythiazox 

residues in bell pepper ranged from O. I 74-0.456ppm (Onager®) and O. l 39-0.363ppm 

(Hexygon®). Adequate storage stability data are available to support sample storage durations 

and conditions. 

5.3.3 Processed Food and Feed (860.1520) 

4947290 l.der.docx, 04/ 14/2015, K.King (wheat) 

Gowan Company submitted a processing study with hexythiazox on wheat. One field trial was 

conducted in the United States during the 2013 growing season in the Environmental Protection 

Agency (EPA) region 11. Table 5.3.1 shows the field trial uses and residue data for this trial. 

Table 5.3.3. Residue Data from the Wheat Processing Study with Hexvthiazox. 

Processed Total Rate PHI Hexythiazox Residues (oom) Processing Factor2 

RAC Commodity lb ai/A (day) Analyte 1 Average' Analyte I Median3 

(g ai/ha) 

Grain (RAC) ND,ND <0.02 -- --

Wheat AGF Ix 0. 17 1, 0. 168 0. 170 >8.5 NA 

Grain (RAC) 0.0009, ND 0.02 -- -- Bran 0.009, 0.012 <0.02 NC NA 

Wheat Flour 5x ND, ND <0.02 NC NA 

Middlings ND, ND <0.02 NC NA 

Shorts ND, ND <0.02 NC NA 

Germ 0.011 , 0.010 <0.02 NC NA 1 ND = Nondctcctable (<LOO). TI1e LOQ was 0.02 ppm, and the LOO was 0.007 ppm. Residues between the LOO and LOQ 

arc in parentheses. The LOQ was used for residues <LOQ in calculating average residues and processing factors. 2 Processing Factor = [Measured residue for analyte in the processed fraction] I !Measured residue for analyte in the RACJ. C = 

ot calculated: residues "ere below the LOQ in the R/\C and processed fraction .. 3 Median processing factor is N/\ (not appl icable) because there was only one processing trial. 

Page 9 of 15 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode D427236 

Conclusions 

Processing studies were completed at l x the application rate and at 5x the application rate. A 

comparison of Ix wheat grain (RAC) and aspirated grain fraction (AGF), indicated that 

hexythiazox residues concentrate in AGF (processing factor of >8.5x). At the 5x plot, residues of 

hexythiazox were below LOQ in/on samples of wheat gra in and processed commodities so 

processing factors were not calculated. 

5.3.4.1 Dietary Burden 

Table 5.3.4.1. Calculation of Dietary Burdens of Hexythiazox Residues to Livestock. 

Indicate if 

% Dry HAFT or Feedstuff Type 1 

Matter2 %Diet2 Median3 

Beef Cattle (R = 15%; CC= 80%; PC = 5%) 

Sorghum, AGF cc 85 5 Median 

Sorghum, Grain cc 86 40 Median 

Corn, Field, Grain cc 88 35 Median 

Cotton, Meal PC 89 5 Median 

Wheat, Hay R 88 15 Tolerance 

TOTAL BURDEN -- -- Dairy Cattle (R = 45%; CC = 45% ; RC = 10% ) 

Corn. Sweet. Cannery Waste cc 30 10 Median 

Sorghum, Grain cc 86 35 Median 

Alfalfa, Meal PC 89 10 Highest 

Residue 

Grass, Forage R 25 45 Highest 

Residue 

TOT AL BURDEN -- -- Swine (CC = 85%; PC = 15%) 

Sorghum, Grain cc 86 80 Median 

Com, Field, Grain cc 88 5 Median 

Alfalfa, Meal PC 89 5 Highest 

Residue 

Cowpea, Seed PC 88 10 Median 

TOTAL BURDEN -- -- Poultry (CC = 75%; PC = 25%) 

Sorghum, Grain cc 86 75 Median 

Alfalfa, Meal PC 89 5 Highest 

Residue 

Cowpea, Seed PC 88 10 Median 

Cotton, Meal PC 89 10 Median 

TOT AL BURDEN -- -- 1 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate. 2 Table I Feedstuffs (July 2008). 

Page 10of 15 

Residue Level 

(ppm) 

5.4 

0.82 

0.02 

0.0002 

30 

--

0.6 1 

0.82 

10.3 

17.1 

--

0.82 

0.02 

10.3 

0.02 

--

0.82 

10.3 

0.02 

0.00 

--

Dietary 

Contribution 

(ppm)4 

0.32 

0.38 

0.01 

0.00 

5.11 

5.82 

0.20 

0.33 

1.16 

30.78 

32.47 

0.66 

0.00 

0.52 

0.00 

1.1 7 

0.62 

0.52 

0.00 

0.00 

1.13 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

3 For cotton meal: Refer to DP#s 24763 1 and 260343, T. Bloem, 3/20/00. For cow pea seed: Refer to DP#s 

364502 and 364504, D. Davis, 1/ 19/ 10. For cotton meal, the tolerance value for cotton seed and the processing 

factor for meal were used because a median residue value for cotton seed could not be determined. 4 Contribution = ([tolerance /% OM] X % diet) for beef and dairy can le; contribution = ([tolerance] X % diet) for 

poultry and swine. 

5.3.4.2 Estimated Secondary Residues in Livestock 

Table 5.3.4.2.1. Summary of Ruminant Feeding Study and Projected Residues Based on Current MRBDs. 

Maximum Residue Levels 

(ppm) at the Three Dosing Tissue Residue to Dosing Projected Residue based on Tissue to 

Levels 1 Level Ratios2 Feed Ratios and Current MRBD3 

Beef Cattle Dairy Calllc Swine 

Commodity 5 ppm 15 ppm SO ppm Sppm l S ppm SO ppm (2.89 ppm) •.5 (32.S ppm) •.5 (1.28 ppm) •.5 

Milk <0.01 <0.01 0.03 NC NC 0.0006 <0.0 1 0.02 <0.01 

Liver <0.01 0.09 0.186 NC 0.0060 0.0037 <0.0 1 0.19 <0.0 1 

Kidney 0.02 0.02 0.03 0.0040 0.00 13 0.0006 0.01 0.04 <0.01 

Fat <0.01 0.01 0.03 NC 0.0007 0.0006 <0.01 0.02 <0.01 

Muscle <0.0 1 <0.01 <0.01 NC NC NC <0.0 1 <0.01 <0.01 

NC = not calculated since quantifiable residues were not seen in tissue at dose level. 1 Combined residues ofhexythiazox and metabolites containing the (4-chlorophenyl)-4·methyl-2-oxo-3-thiazolidine moiety: 2 Tissue residue .;.. Dosing level 3 The tissue to feed ratio from the dosing level closest to the calculated MRBD was used to determine projected residues. 4 Maximum Reasonably Balanced Diet Burden (M Rl3D). 5 Projected residues for beef cattle and dairy cattle derived from 5 ppm dosing level. Dairy cattle milk residue derived from 50 

ppm dose level since residues were not quantifiable at 15 ppm dose level. all other dairy cattle tissue residues derived from 15 ppm 

dose level. 

Table S.3.4.2.2. Summary of Poultry Feeding Study and Projected Hexythiazox Residues 

Maximum Residue Levels Projected Residue based 

(ppm) at the Three Dosing Tissue Residue to Dosing on Tissue to Feed Ratios 

Levels 1 Level Ratios2 and Current MRBD3 

Poultry 

Commodity S ppm IS ppm SO ppm S ppm IS ppm SO ppm 

( 1.23 ppm)' 

Egg 0.058 0. 16 0.36 0.012 0.011 0.0072 0.01 

Liver 0.029 0.069 0.12 0.0058 0.0046 0.0024 0.01 

Kidney < 0.01 0.017 0.035 NC 0.0011 0.0007 <0.01 

Fat 0.053 0.080 0. 17 0.011 0.0053 0.0034 0.01 

Muscle < 0.01 < 0.01 < 0.01 NC NC NC <0.01 

NC= not calculated since q uantifiable residues were not seen in tissue at dose level. 1 Combined residues ofhexythiazox and metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety: 2 Tissue residue .;.. Dosing level 3 The tissue to feed ratio from the dosing level closest to the MR.HD was used to detennine projected residue values. 

~ Maximum Reasonably Balanced Diet Burden (MRBD). 

Conclusions: 

Adequate residue chemistry data are available to determine projected residues in eggs, poultry, 

milk, and rwninant tissues resulting from the existing and newly proposed uses of hexythiazox. 

The currently established tolerances in hog, ruminant (cattle, goats, horse, and sheep), and 

Page 11 of 15 
Hexythiazox Summary of Analytical Chemistry and Residue Dara Barcode D427236 

poultry commodities are adequate to cover secondary residues in livestock consuming 

hexythiazox-treated feedstuffs. 

5.3.5. Food Handling (860.1460) 

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

5.3.6 Water, Fish, and Irrigated Crops (860.1400) 

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

6.0 Tolerance Derivation 

Tolerances have been established for the combined residues of hexythiazox and its metabolites 

containing the ( 4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (expressed as parent) in 

or on various plant and li vestock commodities [40 CFR §180.448(a-c)]. 

Tolerances for all wheat commodities, except aspirated grain fractions (AGF), were proposed by 

the registrant. The proposed wheat tolerances are equal to the tolerances that HED recommended 

in 2012 and are therefore acceptable (0396862, 0. Drew, 06/18/2012). AGF tolerance is 

established at 5.0 ppm which is greater than the HAFT (0.17 ppm) multiplied by the processing 

factor (8.5x) from the recentl y submitted processing study (4947290 1.der.docx, K.King, 

04/ 14/2015). 

Page 12of15 
Hexythiazox Summary of Analytical Chemistry and Residue Data 

Appendix 1. Field Trial Geographic Distribution 

Data Evaluation Record, MRID 49465401. 04/ 14/20 15, K.King 

Barcode D427236 

Field trial's locations and regions are explained in detail in the data evaluation record for 

pepper/eggplants. 

Page 13 of l 5 
Hexythiazox Summary of Analytical Chemistry and Residue Data Barcode 0427236 

Appendix 2. International Residue Limits Table 

Table Bl. Summary of US and International Tolerances and Maximum Residue Limits for 

Hexvthiazox 

Residue Definition: 

us Canada Mexico2 Codex 

40 CFR 180.448: None Plant commodities: Hexythiazox 

Animal commodities: Sum of 

Plant/Livestock: Hexythiazox and its hexythiazox and all metabolites 

metabo lites containing the (4-chlorophenyl)-4- containing the 

methyl-2-oxo-3-thiazol idine moiety (expressed trans-5-( 4-chlorophenyl)-4-

as parent) methyl-2-oxothiazolidinemoiety (PT- 1-3), expressed as 

hexythiazox 

The residue is fat-soluble 

Commodity' Tolerance (ppm) / Maximum Residue Limit (mf?/ kJ{) 

us Canada Mexico2 Codex 

Wheat, Forage 6.0 

Wheat, Hay 30 

Wheat, Grain 0.02 

Wheat, Straw 8.0 

Pepper/Eggplant Crop Subgroup 8- 1.5 0.1 eggplant 

108 

Completed: M. Negussie; 04/28/ 15 

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant. 

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

Page 14of15 
Hexythiazox Summary of Analytical Chemistry and Residue Data 

Appendix 3. OECD MRL Calculation Procedure Inputs/Outputs 

Hexythiazox 

Pepper/ Eggplant Subgroup 8-lOB 

USA 

Total number of data (n) 

Percentage of censored data 

Number of non-censored data 

Lowest residue 

Highest residue 

Median residue 

Mean 

Standard deviation (SD) 

Correction factor for censoring (CF) 

Proposed MRL estimate 

- Highest residue 

- Mean + 4 SD 

- CF x 3 Mean 

Unrounded MRL 

Rounded MRL 

High uncertainty of MRL estimate . 

[Small dataset] 

Residues 

(mg/kg) 

0.151 

0.183 

0.162 

0.234 

0.069 

0.187 

0.191 

Page 15 of 15 

7 

0% 

7 

0 . 069 

0 . 234 

0.183 

0 . 168 

0.051 

1.000 

0.234 

0 . 372 

0.505 

0 . 505 

0.5 

Barcode 0427236 
Hexythiazox [PC Code 128849]/Gowan Company 

B.7.7 

B.7.7.1 

B.7.7.2 

B.7.7.3 

B.7.7.3.1 

Document ID: 

Report: 

Guidelines: 

Effects of Industrial Processing and/or Household Preparation 

(Annex IIA 6.5; Annex IIIA 8.5) 

Nature of the Residue 

(Annex IIA 6.5.1 ; Annex IHA 8.5.1) - Not a data requirement in North America 

Distribution of the Residue in Peel/Pulp 

(Annex HA 6.5.2; Annex IllA 8.5.2) 

To be included if available. 

Magnitude of Residues on Set of Representative Processes 

(Annex HA 6.5.3; Annex IIIA 8.5.3) 

Wheat 

MRID No. 49472901 

Wyatt, D. (2014) Magnitude of the Residue of Hexythiazox in Wheat 

Aspirated Grain Fractions and Processed Commodities Following One 

foliar Application of Onager® 1 E Miticide (20 13). Report Numbers: 

TCI- 13-360, 69607. Unpublished study prepared by The Carringers, Inc. 

247 p. 

EPA OCSPP Harmonized Test Guideline 860.1 520 Processed Food/Feed 

(August 1996) 

PMRA Regulatory Directive DIR98-02 - Residue Chemistry Guidelines, 

Section I 0 - Processed Food/Feed 

OECD Guideline 508 Magnitude of the Pesticide Residues in Processed 

Commodities (October 2008) 

GLP Compliance: No deviations from regulatory requirements were reported which would 

have an impact on the validity of the study. 

Acceptability: 

Evaluator: 

The study is considered scientifi call y acceptable. The acceptability of this 

study for regulatory purposes is addressed in the forthcoming U.S. EPA 

Residue Chemistry Swnmary Document, DP# 423491. 

Katelynn E. Kin ~ 'i- W~ L(-(l(-\ 5 

Note: This Data Evaluation Record (DER) was originally prepared under contract by Versar. Inc. (6850 Versar Center. 

Springfield, VA 2215 1: submit1ed 3116/15). The DER has been reviewed by I IED and revised to renect current Office of 

Pesticide Programs (OPP) policies. 

EXECUTIVE SUMMARY 

Gowan Company has submitted a processing study with hexythiazox on wheat. Jn one field trial 

conducted in the United States in WA during the 2013 growing season, two treated plots 

received a single foliar broadcast application of a I lb ai/gal emulsifiable concentrate (EC) 

formulation of hexythiazox (Onager® IE Miticide) at 0.1873 lb ai/ A (0.2099 kg ai/ha; Trt2, Ix) 

for generation of aspirated grain fractions (AGF) and at 0.9392 lb ai/A (1.053 kg ai/ha; Trt 3, 5x) 

for generation of processed commodities. Applications were made to the treated plots at the late 

EPA MRIO #: 4947290 1 

Page I of9 
Hexythiazox [PC Code 128849)/Gowan Company 

boot stage (prior to head emergence) using ground equipment (tractor-mounted boom sprayer) at 

a spray volume of 15 gal/ A ( 140 L/ha). A nonionic surfactant (NIS) was added to the spray 

mixtures for both applications. Wheat grain was harvested at maturity (BBCH 89; fully ripe, 

grain hard) at a preharvest interval (PHI) of 74 days. Samples from the Trt 2 plot were processed 

into AGF, and samples from the Trt 3 plot were processed into bran, flour, middlings, shorts, and 

germ using simulated commercial procedures. Processing was conducted by GLP Technologies 

(Navasota, TX). Adequate descriptions were provided of the processing procedures, including 

material balance summaries. 

Samples were placed in frozen storage at the field site and were maintained frozen during 

shipping and storage prior to processing and analysis. Processing took place within 55-62 days 

(l.8-2.0 months) of harvest. The maximum storage intervals for samples from 

harvest/processing to extraction were 77 days (2.5 months) for wheat grain (RAC) and 11 -19 

days for AGF and processed commodities. Samples were analyzed within 2-6 days of extraction. 

The available freezer storage stability data indicate that residues of hexythiazox were stable 

when stored frozen in wheat grain for up to 287 days (9.4 months) (refer to DP# 396862, 

6/ 18/ 12, 0. Drew). Storage stability data are not needed to support the processed commodities 

since storage duration was <30 days. The available storage stability data are adequate to support 

the storage conditions and durations for samples from the submitted processing study. 

Samples were analyzed for residues of hexythiazox and its metabolites containing the ( 4-

chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (PT-1-3) using a common moiety 

LC/MS/MS method, Morse Laboratories Analytical Method #Meth-220. Acceptable method 

validation and concurrent recoveries were reported for samples of wheat grain (RAC), AGF, and 

processed commodities fortified with hexythiazox at 0.02-2 ppm, thus validating the method. 

The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) 

was 0.02 ppm in all wheat matrices. The fortification levels used in concurrent method recovery 

were adequate to bracket expected residue levels. Concurrent recoveries were corrected if 

needed for apparent residues in controls if needed; residues in the treated samples were not 

corrected for apparent residues in controls. 

Jn one trial conducted in WA reflecting a single foliar broadcast application of the 1 lb ai/gal EC 

formulation of hexythiazox at a rate of 0.1873 lb ai/A (0.2099 kg ai/ha; Ix), average residues of 

hexythiazox were below the LOQ (<0.02 ppm) in/on samples of wheat grain (RAC) and 0.170 

ppm in/on AGF. In a second plot reflecting application at 0.9392 lb ai/A (1.053 kg ai/ha; 5x), 

residues were below the LOQ (<0.02 ppm) in/on samples of wheat grain and all processed 

commodities. 

A comparison of the residues in/on wheat grain (RAC) from the Ix plot with those in AGF 

indicated that residues of hexythiazox concentrated in AGF (processing factor of>8.5x). 

Because residues of hexythiazox were below the LOQ in/on all samples of wheat grain and 

processed commodities from the 5x plot, processing factors were not calculated. 

The observed processing factor (for AGF) does not exceed the maximum theoretical 

concentration factors of 7.7x for wheat bran, I .4x for flour and 8.3x for shorts (based on 

separation into components; OCSPP 860.1520, Table 3). 

EPA MRID #: 49472901 

Page 2 of9 
Hexythiazox [PC Code 128849]/Gowan Company 

I. MA TERJALS AND METHODS 

A. MA TERJALS 

Table B.7.7.3.1-1. Nom enclature for H exythiazox. 

Common name Hexythiazox 

Ide ntity trans-5-( 4-ch lorophcnyl )-N-cyclohcxyl-4-methyl-2-oxo-3-

thiazolidinccarboxamide 

CAS no. 78587-05-0 

Company experimental name DPX-Y5893 

Other synonyms (if applicable) A-73 

H3C )lvD -

Cl ~ /; SAO H 

Common name PT-1-3 (common moiety) 

Identity 1rans-5-(4-ch lorophen yl )-4-meth y 1-2-oxoth i azo I id i ne 

Compa ny experimental name one 

Other synonyms (if applicable) None 

1-1.C , H 

N 

Cl f ~ 

- s~o 

B. Study Design 

1. Test Procedure 

One trial was conducted on wheat in WA reflecting foliar broadcast application of a 1 lb ai/gal 

emulsifiable concentrate (EC) fonnulation of hexythiazox (Onager® IE Miticide) at 0.1873 lb 

ai/A (0.2099 kg ai/ha; Ix) for generation of AGF and at 0.9392 lb ai/A ( I .053 kg ai/ha; 5x) for 

generation of processed commodities. 

Location and detailed use pattern for the trial is provided in Table B.7.7.3. 1-2. 

Table B.7.7.3.1-2. Study Use Pattern. 

Location : End-use Plot Method of Application: Volume Rate per Retreat- Total Surfactant/ 

City. State: Product 1 Timing of Application (gal/A) Application men\ Rate Adjuvant2 

Year [Ln1a] (lb ai/A) Interval (lb ai/A) 

(Trial ID) [kg ai/ha] (days) [kg ai/ha] 

Ephrata. WA: I lb ai/gal Trt 2 I. Foliar broadcast: BBCI I 45. 15 0. 1873 ·- 0. 1873 NIS 

2013 (TCI- EC ( Ix} late boot stage (1401 [0.20991 ro.20991 

13-360-0 1) Tn 3 I. Fol iar broadcast: 13BCI I 45, IS 0.9392 -- 0.9392 NIS 

(Sx) late boot stage 11 40] 11.053] 11 .053] 

EPA MRID #: 49472901 

Page 3 of9 
Hexythiazox [PC Code 128849]/Gowan Company 

1 A I lb ai/gal cmulsifiablc concentrate (EC) formulation of hcxythiazox (Onager® IE Miticidc). containing a nominal 11.8% 

hcxvthiazox. was used. 2 NiS = Non-ionic surfactant: R- 11 applied at 0.25% v/v 

Sample Handling and Preparation 

Single control and two treated bulk samples (176-469 kg) of wheat grain were collected, one 

from each of the test plots (control, lx, and 5x). Samples were placed in frozen storage at the 

field sites within 1.27 hours of collection. The samples were shipped within 20 days of 

collection via ACDS freezer truck to the processing facility, GLP Technologies (Navasota, TX). 

At the processing facility, samples were stored frozen (:510 °F) prior to and following processing. 

Processing took place within 55-62 days (l.8-2.0 months) of harvest. The grain, AGF and 

processing samples were shipped frozen on dry ice, overnight via FedEx, to the analytical 

laboratory, Morse Laboratories LLC (Sacramento, CA) within 2-9 days of completion of 

processing. At the analytical laboratory, samples were stored frozen (-25 to -10 °C) until 

homogenization and analysis. Prior to analysis, samples of wheat grain (RAC), bran and germ 

samples were homogenized in the presence of dry ice. Samples of AGF, flour, middlings and 

shorts required no additional grinding; they were used as received from the processing lab. 

Sample Processing 

The processing procedures simulated commercial operations of wheat production as closely as 

possible to generate the required fraction of wheat grain (RAC) and the processed fractions, with 

some variations to commercial methods. Adequate descriptions of the processing procedures 

were provided, including material balance summaries. Processing flowcharts for wheat 

processed fractions, copied without alteration from MRID 4947290 I, are presented in Figures 

B. l. (AGF) and B.2 (bran, flour, middlings, shorts, and germ). 

EPA MRJD #: 4947290 1 

Page 4 of 9 
J-lexythiazox [PC Code 128849]/Gowan Company 

FIGURE B.l. Processing Flowchart for Wheat Aspirated Grain Fractions. 

Sample No. 2 (Treated. Trt. 2) Bulk Sample No. TCJ-13-360-01-02 

COMMODITY (WHEAT) 792.8 lbs. 

I 

Drying N/A lbs. (After drying) 

700.0 lbs. used for genera~on 

Aspiration 0.3 lbs. 

I 

Classification 152.2 g Classified 

ASPIRATED GRAIN FRACTION > 2360 micron 35. 7 g 

ASPIRATED GRAIN FRACTION> 2000 micron ..L£g 

ASPIRATED GRAIN FRACTION> 1180 micron~ 

ASPIRATED GRAIN FRACTION > 850 micron 0.4 g 

ASPIRATED GRAIN FRACTION> 425 micron J..:.4..9 

ASPIRATED GRAIN FRACTION< 425 micron 111 .6 g 

Amounts recombined for ASPIRATED GRAIN FRACTION: 

1.2 g < 2360 micron and > 2000 micron 

0.9 g > 1180 micron 

0.4 g > 850 micron 

1.4 g > 425 micron 

111 .5 g < 425 micron 

ASH CONTENT: 10.6 % 

EPA MRID #: 49472901 

Page 5 of9 
Hexythiazox [PC Code 128849]/Gowan Company 

FIGURE B.2 Processing Flowchart for Wheat Bran, Flour, Middlings, Shorts, and Germ 

Sample No. 3 <Treated. Trt. 3) Bulk Sample No. TCl-13-360-01-03 

WHOLE WHEAT 373.7 lbs. 

I 

Drying 

I 

Aspiration 

I 

Screening 

n/a lbs. Dried Wheat 

JLZ_lbs. LIGHT IMPURITIES• 

.. 1.2.Jbs. LARGE SCREENINGS* 

4.1 lbs. SMALL SCREENINGS* 

367.9 lbs. CLEAN WHEAT* 

GERM RECOVERY --~- MlllNG 

300.0 lbs. used 35.0 lbs. used 

24.2 lbs. water added 3.0 lbs. water added 

Condltfonlng & Recovery (Break.Ing & Sieving) 

I 

GERM 

_Q..,dJbs. 

BREJFLOUR 

9.0 lbs. 

l 

REDUCTION FLOUR 

· -2Jllbs. 

MIDDLINGS 

17.4 lbs. 

--1- 2.2 lbs removed for samplo 

(Reductio1: Sl...,ng) 

y 

SHORTS 

10.3 lbs. 

i 

BRAN 

11.2 lbs. 

-,- Brar~ ~ 

BRAN 

10.8 lbs. 

Reduction and Break Flour combined to produce 11. 7 lbs. of Flour 

• After aspiration and screening, there is an unexplained weigh increase of 0.2 lbs. 

2. Description of Analytical Procedures 

Samples were analyzed for residues of hexythiazox and its metabolites containing the (4-

chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (PT-1-3) using a common moiety 

LC/MS/MS method, Morse Laboratories Analytical Method #Meth-220, entitled "Determination 

of Hexythiazox In/On Various Matrices.'· The method was verified on wheat grain, bran, flour, 

EPA MRID #: 49472901 

Page 6 of9 
Hexythiazox [PC Code 128849)/Gowan Company 

and germ prior to the study. A complete description of the method, including any modifications, 

was included in the submission. 

Briefly, samples were hydrated in water then extracted twice by homogenization with 

methanol:water (70:30, v:v), centrifuged, and filtered. The extracts were combined and brought 

to volume with methanol. An aliquot of the combined extracts was concentrated and then diluted 

with deionized water. Base (0.5 N NaOH) was added, and the mixture underwent hydrolysis for 

30 minutes in a 60 °C water bath. The hydrolysis mixture was adjusted to pH 6 and cleaned up 

using C 18 solid phase extraction; residues were eluted with acetonitrile (ACN). The eluate was 

brought to volume with HPLC water, resulting in a composition of ACN:water (22:78, v:v), and 

analyzed for hexythiazox (as PT- 1-3) by LC/MS/MS. Residues determined as PT- 1-3 were 

expressed in hexythiazox equivalents using a molecular weight conversion factor of 1.55. 

The LOQ (determined as the LLMV) was 0.02 ppm in all wheat matrices. The limit of detection 

(LOD), estimated to be - 1 /3 of the LOQ, was 0.007 ppm. 

II. RESULTS AND DISCUSSION 

Method performance was evaluated by use of method validation and concurrent recovery 

samples. Samples of untreated matrices were fortified with hexythiazox at 0.02- 1.0 ppm for 

method validation and 0.02-2.0 ppm for concurrent recovery. All recoveries were within the 

acceptable range of 70-120%; therefore, the method was considered valid for the analysis of 

hexythiazox residues in/on wheat matrices (Table B.7.7.3. 1-3). The fortification levels bracketed 

the measured residues. Concurrent recoveries were corrected if needed for any apparent residues 

detected in the associated controls samples. 

The detector response was linear (coefficient of determination, r2 0.9987) within the range of 

0. 1-20 ng/mL. Representative chromatograms of control samples, fortifi ed samples, and treated 

samples were provided. The control chromatograms generally had no peaks of interest above the 

chromatographic background. The fortified sample chromatograms contained only the analyte of 

interest, and peaks were symmetrical and well defined. Apparent residues in controls were 

below the LOQ (<0.02 ppm) in/on all matrices. The reported residue values were not corrected 

for apparent residues in controls. Residues determined as PT-1-3 were expressed in hexythiazox 

equivalents using a molecular weight conversion factor of 1.55. 

Table B. 7. 7.3. 1-3. S umma ry o f M ethod Va lida tio n and Procedu ral/Concurren t Recoveries of Hexyth iazox 

from Wheat Matrices. 

Matrix Analyte Fortification ample Recoveries• Mean ± Std. 

Level (ppm) size (n) (%) Ocv.2 

(%) 

Method Validation 

Grain Hcxythiazox 0.02- 1.0 6 75-87 81 ± 4.8 

Germ O.o2-l .O 6 75- 104 90 ± 11 

f-l our 0.02- 1.0 6 75-90 84 ± 5.2 

Bran O.Q2-l .0 6 73-93 82 ± 6.4 

EPA MRID #: 49472901 

Page 7 of9 
Hexythiazox [PC Code 128849]/Gowan Company 

Table B.7.7.3.1-3. Summa ry of Method Validation and Procedural/Concur rent Recoveries of Hexythiazox 

from Wheat Matrices. 

Matrix Analyte Fortilication Sample 

Level (ppm) size (n) 

Concurrent Recoveries 

Grain Hexythiazox 0.02-2.0 2 

J\GF 0.02-2.0 2 

Bran 0.02-2.0 2 

flour 0.02-2.0 2 

Middlings 0.02-2.0 2 

Shorts 0.02-2.0 2 

Germ 0.02-2.0 2 1 Concurrent recoveries were corrected if needed for apparent residues in controls. 2 Standard deviation is not calculated for sample sizes <3. 

Recoveries' Mean± Std. 

(%) Dev.2 

(%) 

70.8 1 76 

71. 86 79 

72. 73 73 

84.89 87 

80.80 80 

80.84 82 

78, 84 81 

Sample storage conditions and durations are summarized in Table B. 7.7.3.1-4. Processing took 

place within 55-62 days ( 1.8-2.0 months) of harvest. The maximum storage intervals for 

samples from harvest/processing to extraction were 77 days (2.5 months) for wheat grain (RAC) 

and 11-19 days for AG F and processed commodities. Samples were analyzed within 2-6 days of 

extraction. The available freezer storage stability data indicate that residues of hexythiazox were 

stable when stored frozen in wheat grain for up to 287 days (9.4 months) (refer to DP# 396862, 

6118112, D. Drew). Storage stability data are not needed to support the processed commodities 

since storage duration was <30 days. The available storage stability data are adequate to suppor1 

the storage conditions and durations for samples from the submitted processing study. 

Table B.7.7.3.1-4. Summary of Storage Conditions. 

Matrix Analyte Storage Temperature Actual Storage Duration ' Interval of Demonstrated 

(OC) Days (months) Storage Stability 

Grain I lexythiazox Frozen at fi eld sites: 77 days (2.5 months) 287 days (9.4 months)2 

AGF <I 0 °F at processing 11 days AGF and processed samples 

Bran facility; -25 to -1 O 0

c 19 days were analyzed within <30 days 

Flour 

at laboratory 19 days of processing: therefore. storage 

Middlings 15 days stability data are not required. 

Shorts 15 days 

Germ 16 days 

1 Interval from harvest/processing to extractton. Samples were analyzed within 2-6 days of extraction. 2 Refer to DP# 396862. 6/18112. D. Drew 

Residues found in samples and processing factors are given in Table B.7.7.3. 1-5. In one trial 

conducted in WA reflecting a single foliar broadcast application of the 1 lb ai/gal EC formulation 

of hexythiazox at a rate of 0.1873 lb ai/A (0.2099 kg ai/ha; lx), average residues ofhexythiazox 

were below the LOQ (<0.02 ppm) in/on samples of wheat grain (RAC) and 0.170 ppm inion 

AGF. In a second plot reflecting application at 0.9392 lb ai/A (1.053 kg ai/ha; 5x), residues were 

below the LOQ (<0.02 ppm) inion samples of wheat grain and all processed commodities. 

A comparison of the residues in/on wheat grain (RAC) from the lx plot with those in AGF 

indicated that residues of hexythiazox concentrated in AGF (processing factor of >8.5x). 

Because residues of hexythiazox were below the LOQ in/on all samples of grain and processed 

commodities from the 5x plot, processing factors were not calculated. 

EPA MRID #: 4947290 1 

Page 8 of9 
Hexythiazox [PC Code 128849]/Gowan Company 

Table 8.7.7.3.1-5. Residue Data from Wheat Processing Study with Hexythiazox. 

Location: City. Commodity Plot Analyte Residues (ppm) Processing Median 

State: Year (Average]' Factor Processing 

(Trial ID) Faetor1 

Ephrata. WA: 2013 Grain (RAC) Tn 2 1-lcxythiazox D. D -- -- (TCI-1 3-360-01 ) (Ix) [<0.021 

AGF 0. 171. 0.168 >8.5 NA 

[0.170] 

Grain (RAC) Tn 3 1-lexythiazox (0.009). D -- -- (5x) 1<0.02] 

Bran (0.009). (0.012) NC NI\ 

[<0.02] 

Flour D.ND c NA 

[<0.02] 

Middlings ND. ND NC NA 

[<0.02] 

Shorts ND. ND NC NA 

[<0.021 

Germ (0.011 ), (0.0 I 0) c I\ 

[<0.021 1 ND = Nondetectable (<LOO). The LOQ was 0.02 ppm. and the LOO was 0.007 ppm. Residues between the LOO and LOQ 

are in parentheses. The LOQ was used for residues <LOQ in calculating average residues and processing factors. 

~ Processing Factor = I Measured residue for analyte in the processed fraction I / [Measured residue for analyte in the RAC]. C = 

ot calculated: residues were below the LOQ in the R/\C and processed fraction .. 3 Median processing factor is NI\ (not applicable) because there was only one processing trial. 

111. CONCLUSIONS 

The wheat processing study is considered scientifically acceptable. In one trial conducted in WA 

reflecting a single foliar broadcast application of the 1 lb ai/gal EC formulation of hexythiazox at 

a rate of 0.1873 lb ai/ A (0.2099 kg ai/ha; Ix), average residues of hexythiazox were below the 

LOQ (<0.02 ppm) inion samples of wheat grain (RAC) and 0.170 ppm inion AGF. In a second 

plot reflecting application at 0.9392 lb ai/A (l.053 kg ai/ha; Sx), residues were below the LOQ 

(<0.02 ppm) in/on samples of wheat grain and all processed commodities. 

A comparison of the residues in/on wheat grain (RAC) from the Ix plot with those in AGF 

indicated that residues of hexythiazox concentrated in AGF (processing factor of >8.Sx). 

Because residues ofhexythiazox were below the LOQ inion all samples of wheat grain and 

processed commodities from the Sx plot, processing factors were not calculated. 

The observed processing factor (for AGF) does not exceed the maximum theoretical 

concentration factors of 7. 7x for wheat bran, l.4x for flour and 8.3x for shorts (based on 

separation into components; OCSPP 860. 1520, Table 3). 

An acceptable method was used for residue quantitation, and adequate storage stability data are 

available to support sample storage durations and conditions. 

REFERENCES 

DP#396862, 6/18/ 12, D. Drew 

EPA MRID #: 49472901 

Page9of9 
Hexythiazox [ 128849]/ Gowan Company 

B.7.6 

B.7.6. 1 

B.7.6.1.1 

Document ID: 

Report: 

Guidelines: 

Residues Resulting from Supervised Trials 

(Annex IIA 6.3; Annex IHA 8.3) 

Residues in Target Crops 

Bell peppers 

MRID No. 49465401 

Wyatt, D. [09/02/2014]. Magnitude of the Residue ofHexythiazox in or on 

Greenhouse Grown Bell Pepper Raw Agricultural Commodities Following 

One Foliar Application of Onager® IE or Hexygon® 50DF Miticide2013. TCl Study Number TCI-1 3-386. Unpublished study prepared by The 

Carringers, Inc., 140 Pages. 

EPA OCSPP Harmonized Test Guideline 860.1500 Crop Field Trials 

(August 1996) 

PMRA Regulatory Directive DIR98-02 - Residue Chemistry Guidelines, 

Section 9 - Crop Field Trials 

PMRA Regulatory Directive DIR20 I 0-05 - Revisions to the Residue 

Chemistry Crop Field Trial Requirements 

OECD Guideline 509 Crop Field Trial (September 2009) 

GLP Compliance: No deviations from regulatory requirements were reported which would 

have an impact on the validity of the study 

Acceptability: The study is considered scientifically acceptable. 

Evaluator: Katelynn E. King ~ £. ~ 4-/L/- ( <; 

EXECUTIVE SUMMARY 

Two side-by-side field trials for hexythiazox on greenhouse grown bell peppers were conducted 

in the United States encompassing North American Free Trade Agreement (NAFT A) Growing 

Regions 3 (FL) and 10 (CA) during the 2013 growing season. 

Two trial locations compared two products, Onager® IE and Hexygon® 50DF, in side-by-side 

trials. At each trial location, one foliar broadcast application was applied for two formulations on 

separate plots. At each trial location each product was applied at a rate of 0.1875 lb ai/ A (0.2 10 

kg ai/ha) one day before harvest. An adjuvant was added to each spray mixture for all 

applications (Table B. 7 .6. 1.1-2). Bell peppers were sprayed at an one day preharvest interval 

(PHI). 

All samples were frozen at the testing facility and during shipping to the laboratory. Samples 

were stored frozen until analysis. The maximum storage interval for samples between harvest 

and analysis was 91 days. Residues of hexythiazox have been shown to be stable in bell peppers 

for up to 91 days under frozen conditions. Adequate storage stability data are therefore available 

to support the storage conditions and intervals for samples in the current trials (Table B. 7.6. 1. 1-

4). 

Samples in the current study were analyzed using the Morse Laboratories Analytical Method# 

Meth-220 to determine residues of hexythiazox. Acceptable method validation and concurrent 

Pa e 1of5 

EPA MRID #: 49465401 
Hexythiazox [ 128849)/ Gowan Company 

recoveries were reported for bell pepper samples at fortification levels of 0.02-1.0 mg/kg (ppm), 

thus validating the method. The limit of quantitation (LOQ) was 0.02 ppm for hexythiazox on 

bell peppers. Individual bell pepper sample residues ranged from 0.139-0.456 ppm. The mean of 

all individual residues is 0.3 14 ppm for Onager® and for Hexygon® it is 0.225 ppm. 

I. MATERIALS AND METHODS 

A. MA TERlALS 

Table B.7.6.1.1 -1. Nomenclature for Hexyth iazox. 

Common name Hexythiazox 

1ra11s-S-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo-3-

Identity thiazolidinccarboxamide 

CAS no. 78S87-0S-O 

Compa ny experimental name Hexygon® SODF Miticide 

Other Synonym Onager® IE Mitieide 

B. Study Design 

1. Test Procedure 

During the 2013 growing season, two side-by-side trials were completed in/on greenhouse grown 

bell peppers. One trial used a formulation that was an emulsifiable concentrate (Onager), and the 

other trial used a dry flowable formulation (Hexygon). (Table B. 7.6.1.1-2). 

Table B.7.6. 1.1-2. Tria l Numbe rs a nd Geographical Locations. 

Crop 

Region Total 

I 2 3 4 s 6 7 8 9 10 I I 12 13 14 

Bell Pepper I I 2 

Locations and detailed use patterns for the trials are provided in Table B.7.6. 1.1-3. 

Table B. 7.6. 1.1-3 Locations a nd detailed use patterns. 

Location : End-use Rate per Application Total Rate Surfactant/ City.State: Product/ Method of Application/ Volume lbs ai/A lbs ai/A Adjuvant Year Formulation Timing of Application gal/A (g ai/ha) (g ai/ha) (% v/v) (Trial ID) (%ai) 

Onagero:Q IE Post-emergence Foliar IS 0. 1872 0. 1872 

Zellwood. FL: Miticide Broadcast/ I D 1311 (0.2098) (0.2098) Triangle DW 

2013 l-lexygon® Surfactant 

(TCl- 13-386-0 I) SODF' Post-emergence Foliar IS 0. 1894 0. 1894 (0.24) 

Miticidc Broadcast/ I DBI-I (0.2 123) (0.2123) 

Onager® IE Post-emergence Fol iar 16 0.1910 0. 1910 

Porterville. C/\: Miticide Broadcast/ I D 131 1 (0.2141) (0.2 141) Pro 90 20 13 

llexygon® (0.2S) (TCl-1 3-386-02) 50DF' Post-emergence Foliar IS 0. 1888 0.1888 

Miticidc Broadcast/ 1 DOI I (0.2 116) (0.2 116) 

DBI-I= Days before harvest 

Bell peppers were grown and maintained according to typical agricultural practices. Irrigation 

Pa e2of5 

EPA MRID #: 49465401 
Hcxythiazox [ 128849)/ Gowan Company 

was used; and no unusual weather conditions were reported during the study. 

Sample Handling and Preparation 

After harvesting, samples were frozen and about 20-27 days later they were shipped in freezer 

trucks to the analytical laboratory. Samples were then stored in a freezer before being ground 

with dry ice. Once samples were homogenized, they were returned to the freezer while the dry 

ice was al lowed to sublime. 

2. Description of Analytical Procedures 

Samples of bell peppers were analyzed for residues of hexythiazox using the Morse Laboratories 

Analytical Method# Meth-220. Method was validated concurrently with study samples on bell 

peppers. 

Briefly, samples were hydrated with water and then extracted with a high-speed homogenizer. 

The samples were spun in a centrifuge and then filtered into a flask. The remaining solids were 

extracted again by hand-shaking with a methanol and water solution. This extraction aliquot was 

filtered and combined with the other filtrates. The combination was rinsed with ethanol. 

All of the fi ltered methanol and water was measured in a graduated cylinde r and then transferred 

into a calibrated test tube for evaporation. The evaporated extracts were then brought to a known 

volume with deionized water. Hcxythiazox was converted into the metabolite PT-1-3 by 

hydrolysis and adjusted to pH 6. The mixture was then purified with Bond Elut® C 18 SPE 

cleanup and then brought to a final volume with high pressure liquid chromatography (HPLC) 

water. Determination of metabolite PT-1-3 was conducted using HPLC employing tandem mass 

spectrometric (MS/MS) detection. The ion transitions monitored for PT-1-3 were 228 ~ 168 for 

quantitation and 228 - 115 for confirmation. The LOQ was 0.02 ppm and the LOD was <0.007 

ppm for hexythiazox. 

II.RESULTS AND DISCUSSION 

Method perfonnance was evaluated during method validation by use of concurrent recovery 

samples. Four samples of bell peppers were fortified at 0.02- 1.0 ppm and concurrent recoveries 

ranged from 75% to 80% with a standard deviation of I .9%. All recoveries were within the 

acceptable range of 70% to 120%; therefore, the method was considered valid for the analysis of 

hexythiazox residues in bell pepper matrices. The fortification levels did bracket the measured 

residues. 

The detector response was linear (coefficient of determination, r2 >0.9999) within the range of 

0.1-20 ppm. Representative chromatograms of control samples, fortified samples and treated 

samples were provided. The control chromatograms generally had no peaks of interest above the 

chromatographic background. The fortified sample chromatogran1s contained onJ y the analyte of 

interest, and peaks were symmetrical and well defined. 

The available freezer storage stability data indicate that residues of hexythiazox were stable 

Pa e 3 of 5 

EPA MRID #: 49465401 
Hexythiazox [ 128849 j/ Gowan Company 

when stored frozen at :S0°C for a variety of crops including tomato (MRID 48867601 and MRlD 

48798701 ). Translating these results to bell pepper covers the maximum storage interval of 9 1 

days incurred in the present magnitude of the residue study. 

Tab le B. 7.6. 1.1-4. S umma ry of Storage C onditions. 

Matrix Storage Temperature Actual Storage Duration Interval of Demonstrated Storage Stability 

(RAC or Extract) !Crop) 

I Sorghum grain. stover: Wheat forage: 

Bell Pepper -25 to <0°C 83-9 1 days Cottonseed; Cotton gin byproducts: I lops: Nut 

Meats: Tomato] 

79-490 days 

The results from these tri als showed that when harvested 91 days after the application at a 

seasonal rate of 0.1875 lb ai/ A (0.2 102 kg ai/ha), residues of hexythiazox in bell pepper ranged 

from 0.139-0.456 ppm (Tables B.7.6. 1. 1-5 and B.7.6.1. 1-6). 

Table B.7.6. 1.1-5. Residue Da ta from Bell Pepper Field Trials with H exythiazox. 

Location: Rate Residues (ppm)1 

City. State; Region Crop/ Variety 

End-Use lbs ai/A Pill 

Year Product (days) Hexythiazox Average 

(Trial ID) (kg ai/ha) 

Zellwood. PL: Bell Pepper/ Onagcr® IE 0. 1872 0.4 17. 0.456 0.437 (0.2098) 20 13 3 Califo rnia 1-lexygon® 0. 1894 1 

(TCl- 13-386-0 I) Wonder 50DF (0.2 123) 0.363. 0.240 0.302 

Porterville. CA: Onager® IE 0. 19 10 0.2 10. 0. 174 0. 192 

2013 10 Bell Pepper/ (0.2 14 1) 1 

(TCl-1 3-386-02) Fantasy Hexygon® 0. 1888 0. 159. 0. 139 0. 149 50or (0.2 11 6) 

1 Expressed as parent equivalents 

Ta ble B. 7.6. 1.1-6. S ummary o f Residues fro m Be ll Pepp e rs Fie ld Trials w ith hexythiazox. 

Total Residues' (oom) 

Crop End Use Applicatio Pil l 

Matrix Analyte Product 

n Rate (days) n Min.

2 Max.2 LAFT3 HArT3 Median3 Mean3 

(lbs ai/A) 

[!!. ai/ha] 

Bell Pepper 

Onager® 0. 1875 IE (0.2 102) I 2 0. 174 0.456 0. 192 0.437 0.3 14 0.3 14 

Bell Mitieide 

Pepper Hexythiazox llexygon® 

5oor 0. 1875 1 2 0. 139 0.363 0. 149 0.302 0.200 0.225 

Miticide (0.2 102) 

1 Expressed as parent equivalents. 2 Values based on tornl numbcr of samples. 1 Values based on per-trial averages. LAFT = lowest average field trial, 111\f-T = highest average field trial. SD = standard 

deviation. For computation of the LAFT. HAFT, median. mean. and standard deviation. values < LOO arc assumed to be at the 

LOQ (0.02 ppm). 

n = number of field trials. 

Il l. CONCLUSIONS 

The bell pepper field trials are considered scientificall y acceptable. The results of the study 

Pa e 4 of5 

EPA MRJD #: 4946540 1 

soi 

0. 173 

0.108 
Hexythiazox [ 128849]/ Gowan Company 

showed that following a single application of 0.1875 lbs ail A with a 1 day PHI, hexythiazox 

residues in bell pepper ranged from 0.174-0.456ppm (Onager®) and O. l 39-0.363ppm 

(Hexygon®). Adequate storage stability data are available to support sample storage durations 

and conditions. 

IV. REFERENCES 

Morse Laboratories, LLC, Analytical Method# meth-220, Original, dated May 6, 2013, entitled 

"Determination of Hexythiazox In/On Various Matrices" with Morse Laboratories Method 

Modifications, dated May 16, 20 I 3. 

0404573, 0410813, 05/02/2013, D. Davis, Hexythiazox. New Uses on Grain Sorghum, 

Pepper/Eggplant Subgroup 8-1 OB, Pome Fruit Group 11-10, Caneberry Subgroup I 3-07 A, Small 

Vine Climbing, Except fuzzy Kiwifruit Subgroup I 3-07F, and Low Growing Berry Subgroup 

13-07G, Summary of Analytical Chemistry and Residue Data. 

Pa c5of5 

EPA MRJD #: 49465401