### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D .C. 20460

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION



### MEMORANDUM



### Date: February 1 1

, 2015

Subject : Trinexapac-ethy l. 

### Sec tion 3 Registration Request to Add New Uses on Rice and

R ye. Summary of Analytical Chemistry and Residue D ata

.

PC Code : 112602

Decision No.: 488373

Petition No.: 4F 8 254

Risk Asse ss ment Type: NA

TXR No.: NA

MRID No.: 49282807



### FROM: 

### Sumitra Bose Biswas

, Chemist

Ri sk Assessment Branch Vl DP Barcode: D424894 Registration No.: 100-727

, 100-949, 100-

1241

Re gul atory Action: Sec t ion 3 new food use registration

CaseNo.: NA

CAS No.: 95266-40-3

40 CF R: § 180.662

# ~ 

# <1 ·**~'WJ1P1.**

Health Effects Division (HE D ; 

### 7509P)

THROUGH: 

### Sheila Pip e r
, Chemist

# ~ Donna Davis, Acting Chief

Risk A ssess ment Branch VI

Hea l th Effec ts Division (7509P)

To: 

### B et h any Benbow, Chemical Risk Manager

Kathr y n Montague, Chemical manag e r
D an Kenny, Branch Chief

Ri sk Management and Implementation Branch I

H erbicide Branch/ Registration Division (7505 P )

Page 1 of 31Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 2 of 31 Summary of Submitted Residue Chemistry Studies

O C S PP 860

Series

Guideline MRID Number Monograph

Annex B

Reference Title

1000, 1500

, 1520 49282807 Nakia Smith, M.S. , (2014). Trinexapac

- Ethyl EC (A7725M)

- Magnitude of the Residues in or on Rice.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 3 of 31 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............ 5

2.0 Regulatory Recommendations

................................ ................................ ............................ 6

2.1 Data Deficiencies/Data Needs

................................ ................................ .......................... 6

2.2 Tolerance Considerations

................................ ................................ ................................ . 6

2.2.1 Enforcement Analytical Method

................................ ................................ ............... 6

2.2.2 Recommended Tolerances

................................ ................................ ........................ 7

2.2.3 Revisions to Petitioned

- For Tolerances

................................ ................................ .... 7

2.2.4 International Harmonization

................................ ................................ ..................... 7

3.0 Introduction

................................ ................................ ................................ ......................... 8

3.2 Physical/Chemical Characteristics

................................ ................................ ................... 9

3.3 Pesticide Use Pattern/Directions for Use (860.1200)

................................ ....................... 9

4.0 Metabolite/Degradate Residue Profile

................................ ................................ .............. 11

4.1 Nature of the Residue

................................ ................................ ................................ ..... 11

4.1.1 Summary of Plant Metabolism (860.1300)

................................ ............................. 11

4.1.3 Summary of Confined/ Field Rotational Crops

................................ ...................... 12

4.2 Comparison of Metabolic Pathways

................................ ................................ .............. 13

4.3 Residues of Concern Summary and Rationale

................................ ............................... 13

5.0 Residue Profile

................................ ................................ ................................ .................. 14

5.1 Residue Analytical Methods (860.1340)

................................ ................................ ........ 14

5.1.1 Data Collection Methods

................................ ................................ ........................ 14

5.1.2 Multi

- Residue Methods (860.1360)

................................ ................................ ........ 15

5.1.3 Tolerance Enforcement Methods

................................ ................................ ............ 15

5.1.4 Submittal of Analytical Reference Standards (860.1650)

................................ ...... 15

5.2 Storage Stability (860.1380)

................................ ................................ .......................... 16

5.3 Residue Data

................................ ................................ ................................ .................. 17

5.3.1 Crop F ield Trials (860.1500)

................................ ................................ .................. 17

DER Reference

................................ ................................ ................................ ..................... 17

5.3.2 Field Rotational Crops (860.1900)

................................ ................................ ......... 22

5.3.3 Processed Food and Feed (860.1520)

................................ ................................ ..... 22

5.3.4 Meat, Milk, Poultry and Eggs

................................ ................................ ................. 25

5.3.5. Food Handling (860.1460)

................................ ................................ ...................... 25

5.3.6 Water, Fish, and Irrigated Crops (860.1400)

................................ .......................... 25Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 4 of 31 5.4 Food Residue Profile

................................ ................................ ................................ ...... 25

6.0 Tolerance Derivation

................................ ................................ ................................ ........ 25

7.0 ChemSAC Reference

................................ ................................ ................................ ........ 26

Appendix A. Field Trial Geographic Distribution

................................ ................................ ....... 27

Appendix B. International Residue Limits Table

................................ ................................ ........ 28

Appendix C. OECD MRL Calculator Rice Grain

................................ ................................ ........ 29

OECD MRL Calculator Rice Grain Rice Straw

................................ ................................ ........... 30

REFERENCES

................................ ................................ ................................ ............................. 31Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 5 of 31 1.0 Executive Summary

Trinexapac

- ethyl is a plant growth reg ulator currently registered to Syngenta Crop P rotection for

use on perennial rye grass grown for seeds in the Pacific Northwest ; cereal grains (barley, oats, triticale and wheat) and sugarcane. Trinexapac

- ethyl is formulated as both a 1 lb/gal emulsifiable concentrate (EC 12% a

. i

. ) under the trade name Palisade TM 

### EC (EPA reg. No. 100

- 949) and 2 lb/gal EC (25.5%, Palisade R 

### 2EC; EPA Reg. No. 100

- 1241).

Syngenta has petitioned to establish a permanent tolerance for residues of trinexapa c

- ethyl in/on rice and rye. The registrant provided field trial data on the use of trinexapac

- ethyl in/on rice

commodities.

Syngenta is proposing the establishment of permanent tolerances for residues of trinexapac

- ethyl,

and its metabolites and degradates in/on rice and rye commodities at the following levels:

Commodities Proposed tolerances, ppm Rice, grain 0.4
Rice, straw 0.07
Rice, bran 1.5 Rice, wild, grain 0.4 Rye, bran 6.0 Rye, grain 4.0 Rye, hay 1.5 Rye, straw 0. 9

The metabolic fate of trinexapac ethyl residues in plants (primary and rotational crops) and

livestock commodities is well understood and the residue s of concern (ROC) in plants (primary and rotational crops) for tolerance establishment and risk assessment purposes include free and conjugated residues of both parent and its acid metabolite, trinexapac

. The nature of the residue in livestock (rum inant and poultry) is well understood and t he residue s of concern (ROC) in livestock (ruminant and poultry) are free and conjugated parent trinexapac ethyl and its acid metabolite

.

Rice field trials have been submitted which are adequate in number and geographic representation, generated by a validated analytical method , and supported by adequate storage stability data. The

recommended tolerances on rye commodities are based on the November 25, 2009 ChemSAC decision that provides an allowance for extrapolating residue data for barley and wheat to

additional small cereal grains.

An acceptable processing study has been provided which shows that residues of trinexapac

- ethyl concentrate in polished rice and bran but do not concentrate in hulls. The processing data supports the proposed tolerance for rice bran at 1.5 ppm.

There are no livestock feed items associated with this petition; therefore a discussion of the magnitude of residues in livestock commodities, as well as the need for livestock tolerances andTrinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 6 of 31 analytical methods is not pertinent to this discussion.

The p r eviously submitted c onfin e d r otational c rop stu d y is a d e qu a te to address rotational crop

considerations for this action

. The current label reflects the 30

- day plantback restriction for

c e r e a l g ra ins and l e a f y v e g e tabl e s based on the existing data

.

Th e re a re no e stablished or pro p osed Cod e x , Can a dian, or Me x ic a n ma x i m um r e sidue lim i ts (M R L s) for trin e x a p a c

- e t h y l i n or o n a n y food or f ee d c rops. There are no issues with respect to international harmonization associated with this petition.

2.0 R egulatory R ecommendations

HED has examined the residue chemistry database for trinexapac ethyl . There are no residue chemistry considerations that would preclude granting the requested trinexapac ethyl tolerances

in/on rye and rice

.

2.1 Data Deficiencies/Data Needs

There are no residue chemistry data deficiencies for this action. A human health risk assessment to support the new use is forthcoming.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Sheila Piper, Human Health Risk Assessment for Registration Review (D413570), 9/12/2013

.


### An adequate enforcement method is available to enforce the proposed rice and rye tolerances for trinexapac

- ethyl, Method GRM020.01A, which utilizes high performance liquid chromatography with triple

- quadrupole mass spectrometry (LC

- MS/MS). Method GRM020.01A includes a strong acid hydrolysis/extraction procedure to release both “free” and “conjugated ” residues of trinexapac

acid . The reported limit of quantitation (LOQ) is 0.010 ppm.

In summary, 10

- g subsamples were refluxed with 200 mL of 80/20 acetonitrile (ACN)/1N hydrochloric acid (HCl) for 300 minutes. An aliquot is mixed well with water and p assed through

a pre

- conditioned C8 SPE cartridge followed by analysis by HPLC

- MS/MS for trinexapac acid

. The limit of quantitation (LOQ) is 0.01 ppm for trinexapac acid

.

HED notes that this method does not convert trinexapac acid to parent equivalents. To lerances are expressed as parent equivalents; therefore the results of the enforcement analysis should include a molecular weight conversion to parent equivalents prior to comparison to the tolerance levels.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 7 of 31 2.2.2 Recommended Tolerances

Permanent tol erances are currently established for residues of trinexapac ethyl including its metabolites and degradates under 40 CFR 180.662(a)(1) in/on various plant and animal

commodities.

The tolerance expression listed in the 40 CFR 180. 662 complies with the HED interim tolerance expression policy (S. Knizner, 5/27/09). Permanent tolerances for trinexapac ethyl should be

established under 180. 662 (a) for the commodities listed below at the HED

- recommended tolerance

levels shown in Table 2.2.2.

Table 2.2.2 . Tolerance Summary for Trinexapac ethyl

. Commodity Established/Proposed Tolerance (ppm) HED

- Recommended Tolerance (ppm) Comments

( correct commodity definition ) 

### Rice, grain 0.4 0.4 NA


### Rice, straw 0.07 0.07 NA


### Rice, bran 1.5 1.5 NA 

### Rice, wild, grain 0.4 0.4 NA 

### Rye, bran 2.5 6.0 NA 

### Rye, grain 2.0 4.0 NA 

### Rye, hay 0.8 1.5 NA


### Rye, straw 0.4 0. 9 NA



### 2.2.3 Revisions to Petitioned

- For Tolerances

The registrant has proposed tolerances for rice commodities, the proposed residue level for each commodity was derived using the OECD MRL calculation. For rye, the registrant proposed tolerances by extrapolating residue data for barley. ChemSAC determined that established tolerances for the cereal grains could be extrapolated to other small grains. Since different tolerances are set for the different cereal grain, HED believes it is more appropriate to establish the rye tolerances at the level of the highes t cereal grain tolerance. Since tolerances for wheat commodities are higher than tolerances for barley commodities, HED recommends establishing the new rye tolerances at the level of the wheat tolerances.

2.2.4 International Harmonization

There are no e stablished or proposed Codex, Canadian, or Mexican maximum residue limits (MRLs) for trinexapac

- ethyl in or on any food or feed crops. However, a variety of European countries, as well as Argentina, Brazil, Japan, Korea, and Australia have established or p roposed MRLs for trinexapac

- ethyl on cereal grains (0.02

- 0.5 ppm ), cereal grain forages and fodders (0.2

- 3 ppm ), sugarcane (0.05

- 0.1 ppm ), sugar forage and fodder (1 ppm ), meat (0.02 ppm ), and/or milk (0.1

- 0.005 ppm ). At this time, there are no issues with respect to international harmonization associated with this petition.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 8 of 31 2.3 Label Recommendations

The proposed label is adequate as submitted. No revisions are requi r ed

.

3.0 Introduction

Trinexapac

- ethyl is a plant growth regulator currently registered for use on grasses grown for seed

, cereal grains (barley, oats, triticale and wheat) and sugarcane

. T rinexapac

- ethyl inhibits internodal elongation and growth in cereal grains, grasses and several dicotyledonous species. It is regist ered in numerous European countries and several Asian and Latin American countries for uses on cereal grains and sugarcane. Tolerances are currently established for residues of trinexapac ethyl in/on food commodities under 40 CFR 180.662, at levels ranging from 0.02

- 40 ppm

.

The nomenclature and physicochemical properties of trinexapac

- ethyl are presented below in

Tables 1 and 2.

Table 1. Trinexapac

- ethyl Nomenclature.
Compound

Common name Trinexapac

- ethyl
Company experimental name CGA163935

IUPAC name ethyl ( RS )

- 4

- cyclopropyl(hydroxy)methylene

- 3,5

- dioxocyclohexanecarboxylate

CAS name ethyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate
CAS registry number 95266

- 40

- 3

End

- use product (EP) 1.0 lb/gal EC (PalisadeTM EC; EPA Reg. No. 100

- 949) 2.0 lb/gal EC (Palisade 2EC; EPA Reg. No. 100

- 1241)
Regulated Metabolite

Common Name Trinexapac
Company Experimental

Name CGA

- 179500

IUPAC name ( RS )

- 4

- cyclopropyl(hydroxy)methylene

- 3,5

- dioxocyclohexanecarboxylic acid

CAS name 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid
CAS registry number 104273

- 73

- 6Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 9 of 31 3.2 Physical/Chemical Characteristics

Trinexapac

- ethyl has a relatively low octanol/water partition coefficient. At pH 5.3, the l og K OW 

### value is 2.44 ( K OW 

### = 275 ). Trinexapac

- ethyl has a low potential to leach into groundwater and is not expected to be volatile because of its low vapor pressure (2.16 x 10

- 3 

### Pa at 25 o 

### C). See Table 3.2 for a listing of trinexapac

- ethyl physical and chemical properties.

Table 3.2 Physicochemical Properties of Trinexapac

- ethyl.

Parameter Value Reference

Melting point/range 36.1

- 36.6°C Provided in MRID

46809305 pH 3.3

Density (20oC) 1.215 g/cm 3

Water solubility (g/L at 25°C) 2.8 at pH 4.9 10.2 at pH 5.5

21.1 at pH 8.2

Solvent solubility Acetone 100% Ethanol 100%

Toluene 100% n

- octanol 100%

n

- hexane 5%

Vapor pressure (25oC) 1.62 x 10

- 5 mm Hg

Dissociation constant, pK

a 4.57

Octanol/water partition coefficient, Log(K OW ) at 25oC 2.44 at pH 5.3

UV/visible absorption spectrum Neutral: 9335 L/mol·cm @ 240.2 nm

13976 L/mol·cm @ 277.4 nm

Acidic: 11712 L/mol·cm @ 240.0 nm

12368 L/mol·cm @380.4 nm

Basic: 21320 L/mol·cm @ 270.8 nm



### 3.3 Pesticide Use Pattern/ Directions for Use (860.1200)

Trinexapac

- ethyl is marketed as an emulsifiable concentrate, wettable powder packed in water

soluble bags, and granule. Syngenta Crop Protection has registered trinexapac

- ethyl for multiple

end

- use products on turf areas such as sod farms, golf courses, sport fields, cemeteri es, and similar areas, and on grasses grown for seed, sugarcane, and cereal grains (wheat, barley, oats, and

triticale ). The label

- required personal protective equipment (PPE) for occupational applicators and handlers is a long

- sleeved shirt, long pants, s hoes, and socks, chemical

- resistant gloves, and protective eyewear. The currently proposed uses on rice and rye are summarized in Table 3.3.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 10 of 31 Table 3.3. Summary of Directions for the Proposed Uses of Trinexapac

- ethyl

Applic. Timing,
Type, and
Equip. EPA Reg.

No.
(formulation
type) Max.

Single
Application

Rate
(lb ai/A) Max. No.

Application

per year Max.

Annual
App.

Rate
(lb ai/A) RTI

(days) PHI

(days) Use Directions and

Limitations

Rice

Post

- emergent

aerial
application to

flooded rice

fields 1.0 lb/gal EC

100

- 949
2.0 lb/gal EC

100

- 1241 0.045 1 0.045 NA 50 For best performance,
apply a single
application to one of
the following growth

stages: Fully tillered, panicle
initiation, or panicle

formation. Do not
apply once internode is

more than 1⁄2 to 3⁄4 inch
in length.

Rye
(same use directions as other small grains/cereals currently on the labels)

Post

- emergent application
(ground or aerial) 1.0 lb/gal EC

100

- 949
2.0 lb/gal EC

100

- 1241 0.11 1

0.11 45 Make applications from
the Feekes growth
stage 4 through Feekes
growth stage 7.

Split applications may

be made at Feekes
growth stage 4

- 5 and
then again at Feeks 7
and 8. Apply in a min

of 20 gal/A. 0.05 2



### Conclusion The proposed label for trinexapac

- ethyl is adequate to allow evaluation of the residue data relative to the proposed use on rice. Label direction for rye are equivalent to the currently registered uses of cereal grains.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 11 of 31 4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue

4.1.1 Summary of Plant Metabolism (860.1300)

DER References: 45898902.der (grass); 45898904.der (spring wheat); 46809306.der (rice) ; Sheila Piper, Trinexapac

- ethyl Summary of Residue Chemistry and Analytical data (D378491), 11/23/2011.



### T he nature of trinexapac

- ethyl residues in rice and rye commodities is understood based on the available rice and grass studies on [1,2,6

- 14 

### Ccyclohexyl]trinexapac

- et hyl

. The major metabolite in rice and grass is acid metabolite

, CGA179500. The parent was detected at 2% of the total radioactive residue (TTR). In rice and grass, the metabolism of 14 

### C

- trinexapac

- ethyl rapidly undergoes hydrolysis of the ethyl ester to form trinexapac. Also, the tricarboxylic acid metabolite,

CGA 275537 was identified at the 4x rate in rice (3

- 17%TRR) at 60 DAT and in grass (9

- 15% TRR). This metabolite has the potential for inhibiting the citric acid cycle. However, given the

levels of e xposure observed in submitted studies, ROCKS does not expect this metabolite to contribute significan tly to risk . Therefore the tricarboxylic acid metabolite does not need to be

included as a residue of concern.

The proposed metabolic pathway of trinexapa c

- ethyl in plants includes hydrolysis of the ester bond to trinexapac. Further degradation proceeds via stepwise oxidation/decarboxylation after cleavage

of the 6

- membered ring yielding saturated and unsaturated tricarboxylated acids.

HED Conclusions :
The residues of concern in plants for tolerance establishment and risk assessment purposes include free and conjugated residues of both parent and its acid metabolite, trinexapac (ROCKS memo
, D390121, 7/12/11).

4.1.2 Summary of Livestock Metabolism (860.13 00)

Ruminants:

S. Piper, D 402207

, 5/23/2012



### No new livestock metabolism study for ruminant was submitted. In previously submitted goat metabolism studies (MRIDs 45898905 and 48043705 ) total of three lactating goats were dosed orally via capsules once a day for 4 consecutive days with [1,2,6

- 14C

- cyclohexyl] trinexapac

ethyl (97.9% radiochemical purity) at a dose of 150 mg ai/goat/day, which was equivalent to 2.92

- 3.21 mg ai/kg body weight/day

.

The s tudy shows that majority of the administered doses was excreted via feces and urine

. Trinexapac

- ethyl was not detected in any goat matrices analyzed. The major 14 

### C

- residue in milk (84

- 97%) and all tissues (84

- 97%) was the acid metabolite, CGA 179500

. The metabolite CGA 113745 was also identified in the liver (16% T otal R adioactive R esidue (TRR) ), kidney (6% TRR) and fat (11%), but was not detected in muscle or milk. However, the CGA 113745 metabolite had no structural alerts and has a carboxyl group that should make it readily excreted, making itTrinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 12 of 31 also of less toxicological concern.

Poultry:
S.Piper, D402207, 5/23/2012



### In a previously reviewed study (MRID 48043704 )

, of 14 

### C

- trinexapac ethyl (cyclohexadione ring label) was administered orally via gelatin capsule to five l aying hens at a nominal rate of 10 ppm in the diet for 10 consecutive days

. The majority of the administered dose (88

- 91%) was found to have been excreted. The TRR were below 0.01 ppm for the edible tissues and egg yolks, therefore

, they were not further investigated. T he major residues in poultry were identified as the parent compound trinexapac

- ethyl (31% TRR) and its acid metabolite CGA 179500 (20% TRR).

The major metabolic pathways both in hens and ruminant are similar which in volves hydrolysis of the ethyl ester to yield trinexapac acid (CGA 179500).

HED Conclusions : The nature of the residue in livestock is adequately understood based on the available ruminant and poultry metabolism studies. Based on the available data, the residues of concern in livestock commodities for tolerance enforcement and risk assessment purposes are free and conjugated trinexapac

- ethyl and the acid metabolite, trinexapac (ROCKS memo , D390121, 7/12/11).

4 .1.3 Summary of Confined / Field Rotational Crops

D378491 , S. Piper 11/23/2011.



### The previously submitted confined rotational crop study is adequate to satisfy data requirements. In this study, sandy loam soil was treated once with 14 

### C

- Trinexapac

- ethyl (66.2 μCi/mg) at a target

rate of 0.312 lb ai /A (0.350 kg ai/ha); actual rates were 0.297

- 0.298 lb ai/A (0.333

- 0.334 kg ai/ha). Rotational crops (lettuce, radish and wheat) were planted at plant

- back intervals (PBI) of 30, 120, and 270 days after treatment (DAT) (309 DAT for radish only) and samples of lettuce (immature and mature), radish tops (mature), radish roots (mature) and wheat (forage, hay, grain and straw) were collected at appropriate intervals. TRR values in all RACs were low; only 30

- day PBI lettuce, wheat forage and wheat hay samples ha d TRR >0.01 ppm. The maximum TRR was 0.017 ppm (30

- day PBI mature lettuce). No parent trinexapac

- ethyl was found as a radiolabeled residue in any extracted RAC at any PBI. In addition, no individual extractable 14 

### C

- residue was found to be ≥ 0.01 ppm for a ny RAC at any PBI. Based on the components identified, the results of the confined rotational crop study suggest that trinexapac

- ethyl is metabolized in rotational crops via a route similar to that demonstrated in primary crops.

HED Conclusions : The submitted confined rotational crop data are adequate to support the requested uses.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 13 of 31 4.1.4 Summary of Metabolites and Degradates

4. 2 Comparison of Metabolic Pathways
S. Piper, D377921 , 11 / 23 /2013.



### The metabolism of trinexapac

- ethyl in crops, livestock, and rats has been well characterized. Metabolism appears to be similar in a variety of plant commodities. Based on the plant metabolism study, major residues identified include parent trinexapac

- ethyl and metabolites trinexapac (CGA 179500), ac onitic acid metabolite CGA 312753, and tricarboxylic acid metabolite CGA 275537. The proposed metabolic pathway of trinexapac

- ethyl in plants includes hydrolysis of the ester bond to trinexapac

. Further degradation proceeds via stepwise oxidation/decarbox ylation after cleavage

of the 6

- membered ring yielding saturated and unsaturated tricarboxylated acids

.

The lactating goats and hen studies show that the majority of the administered doses was excreted

via feces and urine

. R adioactivity in the edible organs and tissues was readily and almost completely extracted, indicating that trinexapac ethyl or its metabolites were not bound in the organs and tissues. The major component of the extractable residue in liver, muscle and fat was the metabolite CGA 113745. However, the CGA 113745 metabolite had no structural alerts and has a carboxyl group that should make it readily excreted, making it also of less toxicological

concern.

The rat metabolism study also shows the trinexapac ethyl rapidly excreted via feces and urine. The major component in urine and fecal extracts was trinexapac, the free acid derivative of trinexapac

ethyl resulting from hydrolysis of the ester bond of the p arent compound accounting for approximately 82.0

– 91.6% of the administered dose. The observed metabolic pathway of trinexapac

- ethyl in livestock is comparable to the rat, which is the hydrolysis of ester bond.

HED Conclusions:

The proposed metabolic path ways in rats, livestock and plants are common. Trinexpac

- ethyl involves hydrolysis of the ethyl ester to yield trinexapac (CGA 179500). Trinexapac undergoes cleavage of the hexane ring to yield the succinic acid metabolite, CGA 313458, which then undergoe s stepwise oxidation/ decarboxylation to yield saturated and unsaturated tricarboxylic acids, such as CGA 275537 (tricarboxylic acid) and CGA 312753 (aconitic acid).

4.3 Residues of Concern Summary and Rationale

ROCKS memo, 7/12/2011, D390121



### For pl ants (primary and rotational crops) and livestock commodities, the ROCKS recommends that parent trinexapac

- ethyl and the metabolite trinexapac ( CGA 179500) be the residues of concern for both the tolerance expression and the risk assessment. For drinking water, a total residue approach should be used for the risk assessment.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 14 of 31 Table 4.3. Summary of Metabolites and Degradates of Trinexapac

- ethyl.

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Primary

Crop Trinexapac

- ethyl parent +

Trinexapac (CGA 179500) 1 

### Trinexapac

- ethyl parent + Trinexapac (CGA 179500)

Rotational Crop Trinexapac

- ethyl parent +

Trinexapac (CGA 179500) Trinexapac

- ethyl parent + Trinexapac (CGA 179500)

Livestock Ruminant Trinexapac

- ethyl parent + Trinexapac (CGA 179500) Trinexapac

- ethyl parent + Trinexapac (CGA 179500) Poultry Trinexapac

- ethyl parent +

Trinexapac (CGA 179500) Trinexapac

- ethyl parent + Trinexapac (CGA 179500) Drinking Water Total residues (parent + identified degradates) 2 

### Not Applicable

1 Please see attached Appendix 1 for parent and metabolite names and structures.

2 A total major residue approach is recommended, including parent and major environmental degradates CGA

179500, CGA

- 313458, the open chain cyclohexane ring, and the unidentified hydroproduct M3.



### 5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1 .1 Data Collection Methods

D378491 , S. Piper 11/23/2011.



### Rice field trial s amples were analyzed for residues of trinexapac

- ethyl converted to the acid by LC/MS/MS using Syngenta Analytical Method GRM020.01A “Analytical Method for th e Determination of Residues of t rinexapac

- Ethyl as trinexapac acid metabolite ( CGA179500 ) in Crops by LC

- MS/MS,” with minor modifications. This method was previously reviewed under

DP# 378491 S. Piper, 11/23/2011 ) in conjunction with a crop field trial subm ission for barley grain (48043702.der).

Briefly, samples were refluxed with acetonitrile (ACN)/1 N HCl (80:20 v:v). An aliquot of the extract was applied to a C8 solid phase extraction (SPE) cartridge, and residues were eluted with 0.5% formic acid:ACN (7 0:30 v:v). The eluate was adjusted to volume for LC/MS/MS analysis. The method does not provide for conversion of residues of CGA179500 to parent equivalents; therefore quantifiable residues of trinexapac were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21).

The limit of quantitation ( LOQ ), determined as the lowest level of method validation (LLMV) was 0.01 ppm for trinexapac . The limit of detection (LOD) was not reported.

For concurrent recovery, samples of rice grain were fortified at 0.01 and 0.10 ppm each. The

fortification levels bracketed the measured residues.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 15 of 31 Individual recoveries for the fortification level s at 0.01 and 0.1 ppm are ranged from 72

- 123% and

79

- 108% respectively. The relative standard deviations were <20% for each fortification levels. All recoveries were generally within the acceptable range of 70

- 120%; therefore the method was considered valid for the analysis of residues of trinexapac

- ethyl in rice grain.

HED Conclusions : Analytical methods used to generate the residue data in support of this petition have been adequately validated.

5.1.2 Multi

- Residue Methods (860.1360)

DER reference: 45898908.der ; (D37 8491), S. Piper , 11 /23/2011.



### Trinexapac

- ethyl (CGA

- 163935) was evaluated using the FDA multiresidue method Protocols C and D, and its acid metabolite, trinexapac, was evaluated using Protocol B. Neither compound was tested using Protocols A and G as they do not contain an N

- methylcarb amate moiety and are not substituted urea compounds, and trinexapac

- ethyl was not evaluated through Protocol B as it has neither an acid nor phenol structure.

Adequate GLC responses were obtained for trinexapac

- ethyl using Modules DG1 and DG13 with

elec tron capture detection, but the GLC responses for trinexapac were poor. The relative retention time (RRT) for trinexapac

- ethyl (compared to chlorpyrifos) was 0.82 and 0.93 for DG1 and DG13, respectively. Following methylation, an adequate GLC response was obtained for methylated trinexapac using Module DG1 (RRT = 0.52). However, neither trinexapac

- ethyl nor methy lated trinexapac were recovere d from the Florisil cleanup procedures. Therefore, testing through Protocols E and F was not conducted.

HED Conclu sions :
T rinexapac

- ethyl was evaluated using the FDA multiresidue method Protocols C and D, and its acid metabolite, trinexapac, was evaluated using Protocol B. These data indicate FDA multi

residue methods are not suitable for determining residues of trinexapac

- ethyl and trinexapac in plant commodities.

5.1 .3 Tolerance Enforcement Methods

Referred to section 2.2.1.

5.1.4 Submittal of Analytical Reference Standards (860. 1650)

The Repository (email: T. Cole 02/09/2015) has the following analytes in stock from Syngenta:

• Trinexapac ethyl, expiration date 10/30/2017.

• Trinexapac acid, expiration date 06/30/2015.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 16 of 31 A reminder to the petitioner, supplies of analytical standards must be replenished as requested by the repository as long as the toleran ce is published in 40 CFR180.662 . The address is as follows:

USEPA National Pesticide Standards Repository/Analytical Chemistry Branch/OPP 701 Mapes Road

For t George G. Meade, MD 20755

- 5350

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

5.2 Storage Stability (860.1380)

M R I D s 4710 1 601 a nd 45898903

, S. Piper, D378491 11/23/2011



### Rice: The available freezer storage stability data on wheat (grain and straw) indicate that residues of trinexapac

- ethyl a nd its regulated metabolite were stable when stored frozen in wheat (grain) for 24 months (45898903.der). The sample storage condition and intervals are summarized in

tables 5.2A and 5.2B

.

Based on the current study, p re

- processing rice grain (RAC) samples were stored frozen a

maximum of 446 days (14.7 months) fr om harvest to extraction, and processed samples w ere stored frozen a maximum of 250 days (8.2 months) from processing to extract ion ( Table 5.2A ). Samples were analyzed within 2

- 4 days of extraction. Processing took place within 184

- 197 da ys (6.1

- 6.5 months) of harvest. Therefore, the available storage stability data are adequate to support the storage conditions and durations for r ice grain (RAC) samples as well as for the processed

commodities of rice for the current petition.

Table 5.2A . Summary of Storage Conditions.

Matrix Storage Temperature (°C) Actual Storage

Duration (days/months) Interval of Demonstrated Storage Stability

Rice grain (RAC) Maintained frozen at

processor (≤

- 12  C ), preparation facility
(<

- 10  C ) and analytical laboratory (≤

- 20  C ) 432

- 446 (14.2

-

14.7) Residues of trinexapac acid were

stable when stored frozen in wheat grain for up to 24 months. Polished rice 246

- 248(8.1

- 8.2)

Hulls 246

- 248 (8.1

- 8.2)

Bran 248

- 250 (8.2)

Conclusions: Since the residues of trinexapac ethyl and its metabolite are stable up to 24 months in wide varieties of crops when stored at ≤

- 20 o 

### C, demonstrates that residues are also stable under the conditions and duration for rice. Therefore, HED concludes that the residues of trinexapac ethyl and its regulated metabolite are stable in rice up to 24 months when stored at ≤

- 20 o 

### C.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 17 of 31 5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)

DER Reference



### Rice : Syngenta Crop Protection, LLC has submitted field trial data (MRID 49282807) for trinexapac

- ethyl on rice from 14 field trials conducted in the United States during the 2012 growing

season in the North American Free Trade Agreement (NAFTA) Growing Zones 4 (AR; 4 trials, LA; 4 trials, MO; 1 trial), 5 (MO; 1 trial), 6 (TX, 2 trials) and 10 (CA; 2 trials).

All trials, except for those listed in the table below (Table 5.3.1.), were separated by >20 miles and

are there fore considered independent (568 _Criteria for Independence of Trials 04/23/2013 (EPA and PMRA)). The trials separated by <20 miles have been assessed for independence as detailed in the table below. HED has determined that three trials in zone 4 (05, 07 and 08) should be considered replicate trials due to similar variety (all semi dwarf), same application dates, spray volume and same adjuvant. This decision is reflected in the total trial count above. The number

and locations of field trials are not in co mpliance w ith OPPTS Guideline 860.1500

. According to the OECD guideline, 16 independent field trials are required for rice. However, HED considers 14

field trial s for rice to be acceptable because while fewer trials are submitted from the area that appears to yield higher residues, use of the OECD calculator yields a recommended tolerance of 0.4 ppm, which is significantly higher than any of the residue values from that region

.

Table 5.3.1. Independent Trial Determination 1



### Trial Nos. Differences Decision

01, 06, and 09 Same location

Variety : Roy J (mid

- season, long grain) vs. CL 261 (medium grain) vs. Wells (short

- season long

- grain, large kernel size) All separate due to variety, different application dates (1

- 6 days), different spray volume (3

- 6 GPA), and/or different adjuvant.

04, 05, 07, 08, 10 Same location (05, 07, 08, 10)

Variety : XL 729 (very early season, long grain, tall), CL 151 (very early season, long grain, semi

- dwarf; 19.5K seed/lb), Cocodrie (very early, short season, long grain, semi

- dwarf, 20.6K seed/lb), Cypress (08 and 10; early, long

- grain,

semi

- dwarf, 19.1K seed/lb) 04 separate due to variety (tall vs.

semi

- dwarf); 10 separate due to different application date (20 days).

05, 07, 08: Replicates due to similar variety (all semi dwarf), same application dates, spray volume and same adjuvant.

11 and 12 Zone : 4 vs. 5 Separate due to Zone

13 and 14 Same location

Variety : Presidio (early season, long grain, semi

- dwarf) vs. Cheniere (very early season, long grain, semi

- dwarf, hi yield).

No other differences in criteria Separates due to the varieties and different application date (8 days).Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 18 of 31 Table 5.3.1. Independent Trial Determination 1



### Trial Nos. Differences Decision

15 and 16 Same location and variety

No other differences in criteria

Residues : <0.01 vs. 0.074 ppm Separate due to different r esidues

1 All assessments are based on the replicate trial guidance presented in draft memo 568 _Criteria for Independence of Trials 04/23/2013 (EPA and PMRA) and have been approved by HED; since the study predates the guidance, the criteria specified in the guidance was not strictly adhered to.



### Each trial consisted of one untreated plot and one treated plot. Each treated plot received a single foliar broadcast spray application of the 2.08 lb ai/gal emulsifiable concentrate (EC) formulation of trinexapac

- ethyl (Trinexapac

- Ethyl EC, A7725M) made at BBCH 30

- 32 (panicle initiation or green ring stag e) at 0.041

- 0.046 lb ai/A/application. Applications were made using ground equipment in spray volumes of 2.4

- 10 gal/A. A nonionic surfactant (NIS) or crop oil concentrate (COC) was included in the spray mixtures for all applications. Samples of rice gra in and straw were harvested at maturity at preharvest intervals (PHIs) of 51

- 100 days. Rice straw is no longer considered a significant livestock feed item and is not further addressed herein. At two trials (AR

trial

- 09 and CA trial

- 15), additional sam ples were collected to monitor residue decline 7 and14 days before and after normal crop harvest; PHIs were 65, 72, 79, 85 and 94 days for trial

- 09 and 85, 92, 99, 106 and 113 days for trial

- 15.

Samples were analyzed for residues of trinexapac

- ethyl det ermined as trinexapac acid using Syngenta Analytical Method GRM020.01A (with minor modifications), a high performance liquid chromatography method with tandem mass spectrometric detection (LC/MS/MS). The limit of quantitation (LOQ, determined as the lowest level of method validation, LLMV) was 0.01 ppm. The method does not provide for conversion of residues of trinexapac acid ( CGA179500 ) to parent equivalents; therefore quantifiable residues of CGA179500 were converted to parent equivalents by the study re viewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21). Acceptable method validation and concurrent recovery data were reported for rice grain fortified with CGA179500 at 0.01

- 1.0 ppm, thus valida ting the method. The fortification levels were adequate to bracket expected residue levels.

The results from the submitted field trials are presented in Tables B.7.6.1.1

- 6 and B.7.6.1.1

- 7. In rice grain harvested at PHIs of 51

- 100 days following a single foliar broadcast application of the 2.08 lb ai/gal EC formulation of trinexapac

- ethyl made at 0.041

- 0.046 lb ai/A, individual sample (and per

- trial average) residues of trinexapac

- ethyl (determined as CGA179500) were

<0.01

- 0.270 ppm (<0.01

- 0.214 ppm ).

In one residue decline trial residues were variable, with the highest residues observed at the target PHI. In the second residue decline trial, residues were below the LOQ in/on all samples; therefore,

residue decline could not be determined.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 19 of 31 Ta ble 5.3. 2 . Residue Da ta from Rice Field Trials with Trinexapac

- Ethyl

. Location: City, State;

Year 2 (Trial ID) Zone Rice Variety Matrix Rate

lb ai/A PHI 3

(days) Residues trinexapac

- ethyl 4 (ppm )

[Average]

Proctor, AR; 2012 (TK0044924

- 01) 4 Roy J Grain 0.045 74 0.069

, 0.059 [0.064]

Pollard, AR; 2012 (TK0044924

- 02) 4 RiceTec XL 729 Grain 0.045 85 0.061

, 0.051 [0.056]
Cheneyville, LA; 2012 (TK0044924

- 03) 4 CL 111 Grain 0.046 53 0.060

, 0.056 [0.058]

Ville Platte, LA; 2012 (TK0044924

- 04) 4 XL 729 Grain 0.046 51 0.026

, 0.025 [0.025]
Washington, LA; 2012 (TK00044924

- 05)

and Washington, LA; 2012 (TK0044924

- 07)

and Washington, LA; 2012 (TK0044924

- 08) 4 CL 151

Cocodrie

Cypress Grain 0.044

0.044

0.046 60

60

60 0.180

, 0.203

, 0.270

,

0.236

, 0.191

, 0.203 [0.214]

Proctor, AR; 2012 (TK0044924

- 06) 4 CL261 Grain 0 .045 68 0.024

, 0.024 [0.024]

Proctor, AR; 2012 (TK0044924

- 09) 4 Wells Grain 0.04 5 65 0.043

72 0.053

79 0.088, 0.075

[0.082]

85 0.061

94 0.070

Washington, LA; 2012 (TK0044924

- 10) 4 Cypress Grain 0.046 54 0.191, 0.203 [0.197]

Fisk, MO; 2012 (TK0044924

- 11) 4 RiceTec XP 753 Grain 0.045 91 0.038, 0.036 [0.037]

Fisk, MO; 2012 (TK0044924

- 12) 5 Francis Grain 0.045 85 0.037, 0.041 [0.039]

East Bernard, TX; 2012 (TK0044924

- 13) 6 Presidio Grain 0.044 90 0.113, 0.113 [0.113]

East Bernard, TX; 2012 (TK0044924

- 14) 6 Cheniere Grain 0.041 75 0.019, 0.019 [0.019]

Porterville, CA; 2012 (TK0044924

- 15) 10 Koshihikari Grain 0.045 85 ND

92 <0.01

99 <0.01, <0.01

[<0.01]

106 <0.01

113 <0.01

Porterville, CA; 2012 (TK0044924

- 16) 10 Koshihikari Grain 0.046 100 0.092, 0. 073 [0. 083 ]

1 A 2.08 lb ai/gal EC formulatioin (A7725M) was used.

2 HED has determined that Trials 05, 07, and 08 are replicate trials.

3 Target PHIs are bolded for decline trials.

4 ND = Not detected (no peak) as reported by the petitioner

. The method determines residues of trinexapac

- ethyl as CGA179500. Residues of CGA179500 were converted to parent equivalents by the study reviewe r using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21)

. Per trial averages were calculated by the study reviewer.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 20 of 31 Table 5.3.2 . Summary of Residues from Rice Field Trials with Trinexapac

- Ethyl.

Crop Matrix Total

Application

Rate

lb ai/A PHI

(days) n 1 Residues (ppm Trinexapac

- ethyl )

Min. 2 Max. 2 LAFT 3 HAFT 3 Median 3 Mean 3 SD 3

Rice Grain 0.041

- 0.046 51

- 100 14 <0.01 0.270 <0.01 0.214 0.0 57 0.0 73 0.063

1 n = number of field trials.

2 Values based on total number of samples.

3 Values based on per

- trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values <LOQ are assumed to be at the LOQ (0.01 ppm for trinexapac

- ethyl as CGA179500)

.

Table 5.3.3. Summary of Residues of Trinexapac

- Ethyl in/on straw.

T r i a l ID ( S t a t e /Y e a r) NAFTA

R e g i on Ri c e V ar i e ty M a t r ix N o m i n a l

T o t al

R a t e 1

(lb a i /A) N o m

i n a l

Sa m p l i ng
E v e n t 2 T r i n e x a p a c

- Et h y l R e s i d u e L e v e ls ( p p m ) 3

C G A 179 5 00 T r i a l M ea n 4

T K 004 4 92 4

- 01 ( A R/ 2012 ) 4 R o y J S tr aw

--- -- ND

--- S tr aw
S tr aw 0. 0 45 M a t u rity 0. 0 12

0. 0 17 0. 0 1 45

T K 004 4 92 4

- 02 ( A R/ 2012 ) 4 Ri ce T e c X L

729 S tr aw

--- -- ND

---

S tr aw S tr aw 0. 0 45 M a t u rity < L OQ ND 0. 0 0 75

T K 004 4 92 4

- 03 (L A / 2012 ) 4 CL 111 S tr aw

--- -- ND

--- S tr aw
S tr aw 0. 0 46 M a t u rity 0. 0 18

0. 0 13 0. 0 1 55

T K 004 4 92 4

- 04 (L A / 2012 ) 4 X L 7 2 9 S tr aw

--- -- ND

--- S tr aw S tr aw 0. 0 46 M a t u rity ND

ND 0. 0 05

T K 004 4 92 4

- 05 (L A / 2012 ) 4 CL 151 S tr aw

--- -- ND

--- S tr aw

S tr aw 0. 0 44 M a t u rity 0. 0 45

0. 0 34 0. 0 3 95

T K 004 4 92 4

- 06 ( A R/ 2012 ) 4 C L 261 S tr aw

--- -- ND

-- S tr aw

S tr aw 0. 0 45 M a t u rity < L OQ

ND 0. 0 0 75

T K 004 4 92 4

- 0 7 (L A / 2012 ) 4 C o c od rie S tr aw

--- -- ND

-- S tr aw

S tr aw 0. 0 44 M a t u rity 0. 0 36

0. 0 35 0. 0 3 55

T K 004 4 92 4

- 08 (L A / 2012 ) 4 C y p r e ss S tr aw

--- -- ND

--

S tr aw

S tr aw 0. 0 46 M a t u rity 0. 0 27

0. 0 24 0. 0 2 55

T K 004 4 92 4

- 09 ( A R/ 2012 ) 4 W e lls S tr aw

-- -- ND

-- S tr aw 0. 0 45 1 4 P M ND

-- S tr aw 7 P M < L OQ

-- S tr aw

S tr aw M a t u rity 0. 0 13

< L OQ 0. 0 1 15

S tr aw 7 AM < L OQ

-- S tr aw 1 4 A M < L OQ

--

T K 004 4 92 4

- 10 (L A / 2012 ) 4 C y p r e ss S tr aw

--- -- ND

---

S tr aw
S tr aw 0. 0 46 M a t u rity 0. 0 44

0. 0 45 0. 0 4 45

T K 004 4 92 4

- 11 ( M O/ 2 0 12 ) 4 Ri ce T e c XP

753 S tr aw

--- -- ND

---

S tr aw
S tr aw 0. 0 45 M a t u rity < L OQ

< L OQ 0. 01Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 21 of 31 Table 5.3.3. Summary of Residues of Trinexapac

- Ethyl in/on straw.

T K 004 4 92 4

- 12 ( M O/ 2 0 12 ) 5 F r a n c is S tr aw

--- -- ND

--- S tr aw S tr aw 0. 0 45 M a t u rity 0. 0 10

< L OQ 0. 0 1

T K 004 4 92 4

- 13 ( T X / 2 0 12) 6 P r e si d io S tr aw

--- -- ND

--- S tr aw
S tr aw 0. 0 44 M a t u rity 0. 0 17

0. 0 23 0. 02

T K 004 4 92 4

- 14 ( T X / 2 0 12) 6 C h e n i e re S tr aw

--- -- ND

--- S tr aw

S tr aw 0. 0 41 M a t u rity ND

ND 0. 0 0 5

T K 004 4 92 4

- 15 (C A / 2012 ) 10 K o s h i h i ka ri S tr aw

--- -- ND

-- S tr aw 0. 0 45 1 4 P M ND

-- S tr aw 7 P M ND

-- S tr aw S tr aw M a t u rity ND

ND 0. 0 05

S tr aw 7 AM ND

-- S tr aw 1 4 A M ND

--

T K 004 4 92 4

- 16 (C A / 2012) 10 K o s h i h i ka ri S tr aw

-- -- ND

-- S tr aw 0. 0 46 M a t u rity < L OQ

0. 0 24 0. 0 17 S tr aw

1 T o t a l R a te = O n e f

o li a r b r o a d ca st a pp li ca

t i o n w a s ma d e a t a no m i n a l r a te o f 0.0 4 5 l b a i/A

2 P M = D a y s p ri o r to m a t u rit y
, A M = D a y s a f t e r m a t u ri t y
, M a t u rity = N o r m a l M a t u rit y ; P P = P re

- p r oce ssi n g

3 L OQ = 0.0 1 pp m ; ND = N o t D e t ec t e d

. 4 Fo r ca l c u l a t i o n o f t h e tri a l m ea n
, if r e si du e s w e re ND a v a l u e o f 0. 0 0 5 ( 1 /2 L OQ) w a s u s e d , if th e va l u e w a s < L OQ t h e va l u e 0.0 1 ( L OQ) w a s u s e d

.



### Rye: The tolerances on rye was requested based on the November 25, 2009 ChemSAC decision that provides an allowance for extrapolating residue data for barley and wheat to additional small cereal grains. Since the tolerances are established for cereals (wheat, barley and oats), the tolerances for rye is translatable to established tolerances of small cereal grains.

Conclusions :

Rice: The rice field trials are considered scientifically acceptable and are adequate in terms of both geographic representation and number. The field portion of the study was adequately documented. An acceptable method was used for quantitation of residues in/ on rice. The data are supported by adequate storage stability data. In rice grain harvested at PHIs of 51

- 100 days following a single foliar broadcast application of the 2.08 lb ai/gal EC formulation of trinexapac

- ethyl ma de at 0.041

- 0.046 lb ai/A, individual sample (and per

- trial average) residues of trinexapac

- ethyl (determined as CGA179500) were <0.01

- 0.270 ppm (<0.01

- 0.214 ppm).

In one residue decline trial residues were variable, with the highest residues observed at the target PHI. In the second residue decline trial, residues were below the LOQ in/on all samples; therefore, residue decline could not be determined.

Rye: no new field trial data were submitted or are required to support the new use and tolerance

on r ye.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 22 of 31 5.3.2 Field Rotational Crops (860.1900 )

Confined rotational crop data were submitted, however

, field rotational data hav e not been provided. S ince the labe l currently ref l ects a 30

- day PBI for cereal grains, field rotational crop data are not required at this time.

5.3.3 Processed Food and Feed (860.1520)

DER referen ce



### Rice : Syngenta Crop Protection, LLC has submitted a processing study with trinexapac

- ethyl o n rice. I n two trials conducted in LA and MO during the 2012 growing season , a single foliar broadcast spray application of the 2.08 lb ai/gal emulsifiable concentrate (EC) formulation of trinexapac

- ethyl (Trinexapac

- Ethyl EC, A7725M) was made at the BBCH 30

- 32 (pa nicle initiation or green ring stage) at an exaggerated rate of 0.134

- 0.135 lb ai/A (~3x the field application rate)

. Applications were made using ground equipment in a spray volume of 10 gal/A. A crop oil concentrate (COC) or non

- ionic surfactant (NIS) was added to the spray mixture for each trial. The study use pattern is summarized in Table 5.3.3 below. Samples of rice grain were harvested at maturity at preharvest intervals (PHIs) of 54

- 91 days and processed into polished rice, hulls

, and

bran us ing s imulated commercial practices. Processing was conducted by GLP Technologies (Navasota, TX).

The processing procedure simulated commercial operations of rice production as closely as possible to generate the required fraction of rice grain (RAC), polished rice, hulls, and bran. A processing flowchart for rice, copied without alteration from MRID 49282807, is presented below in Figure 5.3.3.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 23 of 31 FIGURE 5.3.3. Processing Flowchart for Polished Rice, Hulls, and Bran.

Table. 5.3.3 A Study Use Pattern.

Location: City, State; Year (Trial ID) End

- use

Product 1 Method of Application/

Timing of Application Volume (gal/A) Rate per

Application (lb ai/A) Retreatment

Interval (days) Total Rate

(lb ai/A) Surfactant/

Adjuvant 2

Washington, LA;

2012 (TK0044924

- 10) 2.08 lb

ai/gal EC Foliar broadcast; BBCH

30

- 32 (panicle initiation or green ring stage) 10 0.134

-- 0.134 COC

Fisk, MO; 2012 (TK0044924

- 11) 2.08 lb

ai/gal EC Foliar broadcast; BBCH

30

- 32 (panicle initiation or green ring stage) 10 0.135

-- 0.135 NIS

1 End

- use product is A7725M, a 2.08 lb ai/gallon emulsifiable concentrate (EC) formulation of trinexapac

- ethyl.

2 COC = crop oil concentrate. NIS = non

- ionic surfactant.



### S amples were shipped at ambient temperatures from the testing facility to the processing facility, where they were placed into frozen storage and remained frozen during shipping and storage prior to processing , preparation and analysis. The maximum storage interval for samples was 446 days (14.7 months) for pre

- processing rice grain, 248 days (8.2 months) for polished rice and hulls, and 250 days (8.2 months) for bran from harvest/processing to extraction. Samples were analyzed

within 2

- 4 days of extraction. Processing took place within 185

- 197 days (6.1

- 6 .5 months) of

harvest. S torage stability data are available indicating that residues of CGA179500 were stable

when stored frozen for up to 24 months in/on wheat grain. The available storage stability data areTrinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 24 of 31 adequate to support the storage conditions and durations for rice grain (RAC) samples from t he

submitted rice processing study

. S torage stability data are available indicating that residues of

CGA179500 were stable when stored frozen for up to 24 months in/on small cereal grains.

Therefore the availabl e storage stability data are adequate to supports the storage duration and stability of the processed commodities of rice.

RAC and processed commoditie s were analyzed using Syngenta Method GRM020.01A, which

was discussed in enforcement analytical method Section (section 2.2.1) and has been validated as

an acc eptable data collection method

.

In rice grain harvested at PHIs of 54

- 91 days following a single foliar broadcast application a 2.08 lb ai/gal EC formulation of trinexapac

- ethyl at an exaggerated ra te of 0.134

- 0.135 lb ai/A (~3x the field application rate) , residues of trinexapac

- ethyl determined as trinexapac acid ( CGA179500)

were 0.11

- 0.63 ppm. Residues of trinexapac ethyl , converted to parent equivalents, were 0.11

- 1.04 ppm in polished rice, 0.025

- 0.37 ppm in hulls, and 0.63

- 2.81 ppm in bran.

The processing data indicate that residues of trinexapac acid concentrate in polished rice (1.0

- 1.6x, median processing factor 1.3x) and bran (4.4

- 5.8x, median processing factor 5.1x), but do not concentrate in hulls (0.2

- 0.6x, median processing factor 0.4x).

The observed processing factors calculated in this study were less than the maximum theoretical concentration factors of 7.7x for rice bran and 5.0x for rice hulls (based on separation of

compone nts; OCSPP 860.1520, Table 3).

A s ummary of the residues data from rice processing study is presented in the follow ing tables.

Table. 5.3.3 C

. Residue Data from Rice Processing Study with Trinexapac

- ethyl as CGA179500

Commodity Analyte Residues 1 (ppm)[Average] Processing Factor 2 Median Processing

Factor 3

Washington, LA; 2012 (TK0044924

- 10)

Rice grain (RAC) CGA179500 0.87, 0.79, 0.25 [0.63]

-- -- Polished rice CGA179500 1.04 1.6x 1.3x

Hulls CGA179500 0.37 0.6x 0.4x

Bran CGA179500 2.81 4.4x 5.1x

Fisk, MO; 2012 (TK0044924

- 11)
Rice grain (RAC) CGA179500 0.11, 0.11, 0.11 [0.11]

-- Polished rice CGA179500 0.11 1.0x

Hulls CGA179500 0.025 0.2x

Bran CGA179500 0.63 5.8x

1 The method determines residues of trinexapac

- ethyl as CGA179500. R esidues of CGA179500 were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21)

. 2 Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the RAC]. A separate processing factor is calculated for each proces sed commodity.

3 Median (and also mean in this case) of processing factors for both sites, determined for each matrix.



### ConclusionsTrinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 25 of 31 The submitted processing data are supported by storage stability data and were generated using a

validated enforcement method. The processing data indicate that residues of trinexapac acid concentrate in polished rice (1.0

- 1.6x, median processing factor 1 .3x) and bran (4.4

- 5.8x, median processing factor 5.1x), but do not concentrate in hulls (0.2

- 0.6x, median processing factor 0.4x).

The observed processing factors calculated in this study were less than the maximum theoretical

concentration factors of 7.7 x for rice bran and 5.0x for rice hulls (based on separation of components; OCSPP 860.1520, Table 3).

5.3.4 Meat, Milk, Poultry and Eggs

There are no livestock feed items associated with this petition; therefore a discussion of the magnitude of res idues in livestock commodities, as well as the need for livestock tolerances and analytical methods is not pertinent to this discussion.

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.

5.4 Food Residue Profile

Available metabolism data shows that trinexapac

- ethyl does translocate to the growing shoot when applied as a foliar application. Trinexapac

- ethyl is used at relatively low application rates, and the submitted field trial studies demonstrate that when appl ied at post

- emergence, quantifiable residues are seen in cereal grains treated up to 51

- 100 days before harvest. Also, data from the confined rotational crop study indicate that trinexapac

- ethyl residues are detected (lettuce and wheat) at the 30

- day plan t back interval. Quantifiable residues were only seen in livestock at low

levels in the animal feedstuff associated with this action.

6.0 Tolerance Derivation

T he Agency’s Organization for Economic Cooperation and Development ( OECD) MRL calculator

was used to determine appropriate tolerance levels for the combined residues of trinexapac ethyl and its alcohol metabolite ( rice grain 0.4 and rice straw 0.07 ppm ). The results from the spreadsheet

calculator (appendix C) support the proposed tolerances for both rice straw and grain. The processing data supports the proposed tolerance for rice bran at 1.5 ppm.

For rye, the registrant proposed tolerances by extrapolating residue data for barley. HED concurs that tolerances can be established by translation from other cereal grains, however, s ince tolerancesTrinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 26 of 31 for wheat commodities are higher than tolerances for barley commodities, tolerances for rye

commodities were translated from the higher wheat values.

7.0 ChemSAC Reference

Trinexapac ethyl is not a ne w active ingredient ; therefore . ChemSAC review is not required for

this action.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 27 of 31 Appendix A

. Field Trial Geographic Distribution

NAFTA

Gro w i n g R e g i on T r i a ls C o m p l e t e d a n d
S u b m i t t e d T r i a l N o. T r i a l L o c a t i o n

4 * 11 * T K 004 4 92 4

- 0 1 P r o c t o r, A R

T K 004 4 92 4

- 0 2 Po ll a r d

, A R

T K 004 4 92 4

- 0 3 C h e n eyv ill e
, LA

T K 004 4 92 4

- 0 4 V ille P l a tt e
, L A

T K 004 4 92 4

- 0 5 * W a s h i n g t on
, L A

T K 004 4 92 4

- 0 6 P r o c t o r, A R

T K 004 4 92 4

- 0 7 * W a s h i n g t on
, L A

T K 004 4 92 4

- 0 8 * W a s h i n g t on
, L A

T K 004 4 92 4

- 0 9 P r o c t o r, A R

T K 004 4 92 4

- 10 W a s h i n g t on
, L A

T K 004 4 92 4

- 11 F is k

, M O

5 1 T K 004 4 92 4

- 12 F is k

, M O

6 2 T K 004 4 92 4

- 13 E a st B e r n a r d

, T X

T K 004 4 92 4

- 14 E a st B e r n a r d

, T X

10 2 T K 004 4 92 4

- 15 Po rt e r v ill e
, CA

T K 004 4 92 4

- 16 Po rt e r v ill e
, CA

T o t al 16



### * Even though 16 field trials were submitted from zone 4, HED determined that trial TK0044924

- 05, 07 and 08 are considered as replication due to same variety,

application dates and same spray volume and same adjuvant.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 28 of 31 Appendix B . In ternational Residue Limits Table



## Trinexapac ethyl (PC Code: 112602 )

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 

### Codex 3



### 40 CFR 180. 662 :
Plants: T rinexapac

- ethyl, ethyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate and associated metabolite trinexpac, 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid.



### Commodity 1 

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

US Canada Mexico 2 

### Codex Rice, grain 0.4
Rice, straw 0.07
Rice, bran 1.7 Rice, wild, grain 0.4 Rye, bran 2.5 Rye, grain 2.0 Rye, hay 0.8 Rye, straw 0.4

Completed: Completed: M. Negussie; 11/07/14

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

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

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the f at portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 29 of 31 Appendix C. OECD MRL Calculator Rice Grain Tolerance values were calculated by the OECD MRL Calculator using data from the field trial residue study ( MRID 49282807 ) for a 2.08 lb ai/A Trinexapac ethyl.

Trinexapac

ethyl

Rice

Grain

NAFTA

2.08 lb ai/gal
Trinexapac

- ethyl

Residues (mg/kg) Rice Grain

0.064 NAFTA

0.056 2.08 lb ai/gal

0.058

0.025 Total number of data (n) 14

0.214 Percentage of censored data 0%

0.024 Number of non

- censored data 14

0.082 Lowest residue 0.010

0.197 Highest residue 0.214

0.037 Median residue 0.057

0.039 Mean 0.073

0.113 Standard deviation (SD) 0.063

0.019 Correction factor for censoring (CF) 1.000

0.010

0.083 Proposed MRL estimate

- Highest residue 0.214

- Mean + 4 SD 0.325

- CF x 3 Mean 0.219

Unrounded MRL 0.325

Rounded MRL 0.4Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 30 of 31 OECD MRL Calculator Rice Grain Rice Straw Tolerance values were calculated by the OECD MRL Calculator using data from the field trial residue study ( MRID 49282807 ) for a 2.08 lb ai/A Trinexapac ethyl.

Trinexapac

ethyl

Rice

Straw

NAFTA

2.08 lb ai/gal
Trinexapac

- ethyl

Residues (mg/kg) Rice Straw

0.015 NAFTA

0.008 2.08 lb ai/gal

0.016

0.005 Total number of data (n) 14

0.034 Percentage of censored data 0%

0.008 Number of non

- censored data 14

0.012 Lowest residue 0.005

0.045 Highest residue 0.045

0.010 Median residue 0.011

0.010 Mean 0.015

0.020 Standard deviation (SD) 0.012

0.005 Correction factor for censoring (CF) 1.000

0.005

0.017 Proposed MRL estimate

- Highest residue 0.045

- Mean + 4 SD 0.061

- CF x 3 Mean 0.044

Unrounded MRL 0.061

Rounded MRL 0.07Trinexapac

- Ethyl Summary of Analytical Chemistry and Residue Data DP Number: D424894



### Page 31 of 31 REFERENCES

Subject: M.S. , (2014). Trinexapac

- Ethyl EC (A7725M)

- Magnitude of the Residues in or

on Rice.

From: Nakia Smith

Date: 10/29/08

MRIDs: 49282807

DP#: 402207 Subject: Trinexapac

- ethyl: Revised Application for the Section 3 Registration Action on

Cereal Grains and Sugarcane (PP#0F7720) and Grasses Grown for Seed (PP#0F7719). Summary of Analytical Chemistry and Residue Data.

From: Sheila Piper

To: Bethany Benbow/ Kathryn Montague

Date: 05/23/2012

MRIDs: 42233942

DP#: 390121 Subject: Trinexapac

- ethyl; Report of the Residues of Concern Knowledgebase

Subcommittee (ROCKS)

. From: Elizabeth Holman / Christine L. Olinger

Date: 07/12/2011

MRIDs: NA

DP#: 377921 Subject: Trinexapac

- ethyl: Human Health Risk Assessment for the Section 3

Registration Action on Cereal Grains, Sugarcane, and Grasses Grown for Seed.

From: Sheila Piper

To: Bethany Benbow/ Kathryn Montague

Date: 11 /23/ 2011

MRIDs: NATrinexapac-ethyl [PC C ode l 12602) / SyngentaCrop Protection

, LLC

Processed Food/Feed-Rice



### Primary Evaluator

# -~ Date: 10-MAR-2015

Approve d by

B.7.7

B.7.7.1

B.7

. 7

. 2

8

. 7

. 7 .3

B.7.7

. 3.1 umitra Bose Biswas

, C hemi st

Risk Assessment Branch VI 

### ( RAB V I )



### Health Effects Division (RED ( 7 509 P )

S heila Pi pe r
, Se ni or C hemist

RAB Y [

, HE D (75 0 9 P ) Da te: 10-MAR

- 2015

Effects of Indu str ial Pr ocess ing and/or Household Preparation (Annex IIA 6.5; Annex 

## IIIA 8.5)

Nature of the Residue (Annex IIA 6.5.1; Annex IIIA 

### 8.5.1)-Not a data requirement in North America



### D ist ri bution of the Residue in Peel/Pulp (Annex IIA 6.5.2; Annex IHA 8.5.2)-

To be included if available.



### Magnitude of Residues on Set of Representative Processes (Annex IIA 6.5.3; Annex IHA 8

. 5.3)

Rice

Document ID: MRID No

. 49282807

PMRA No. Not Avai l able 

### Report: Smith

, N. (2014) Trinexapac-Ethyl EC (A7725M)

- Magnitude of the

Residues in or on Rice. Final Report. OLP Study Number: TK0044924,

North Coast Study N umber: 110.046. Unpublished study prepared by Syngenta Crop Protect i o n
, LL C. 222 p. 

### Guidelines: EPA OCSPP Harmonized Test Guideline 860.1520 Processed Food/Feed
(August 1996)

PMRA Regulatory Directive DIR98-02

- Residue Chemistry Guidelines,

Section 1 0

- Processed Food/Feed

OE CD 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: The s tudy is tentatively considered sc ientifi cally acceptable pe ndi ng
submission and evaluation of sto r age stability data for processed

commodities. T h e acceptabi li ty of this study for regu l atory purposes is

addressed in the forthcoming U.S. EPA Residue Chemistry S ummar y Document, DP # 424894.



### Evaluator : Sumitra Bose Biswas

EPA MRID #: 49282807

PMRA # of document: N ot Available Page J of8Trinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 2 of 8 Note: This Data Evaluation Record (DER) was originally prepared under contract by Versar , Inc. (6850 Versar Center, Springfield, VA 22151; submitted 9 / 22 /14 ). The DER has been reviewed by HED and revised to reflect current Office of Pesticide Programs (OPP) policies.



### EXECUTIVE SUMMARY

Syngenta Crop Protection, LLC has submitted a processi ng study with trinexapac

- ethyl o n rice.

In two trials conducted in LA and MO during the 2012 growing season

, a single foliar broadcast spray application of the 2.08 lb ai/gal emulsi fiable concentrate (EC) formulation of trinexapac

ethyl ( Trinexapac

- Ethyl EC, A7725M) was made at the BBCH 30

- 32 (panicle initiation or green ring stage) at an exaggerated rate of 0.134

- 0.135 lb ai/A (~3x the field application rate)

. Applications were made using ground equipment in a spray volume of 10 gal/A. A crop oil concentrate (COC) or non

- ionic surfactant (NIS) was added to the spray mixture for each trial. Samples of r ice grain were harvested at maturity at preharvest inter vals (PHIs) of 54

- 91 days and processed into polished rice

, hulls

, and bran us ing simulated commercial practices. Processing was conducted by GLP Technologies (Navasota, TX). Adequate descriptions were provided of the processing procedures including mater ial balance summaries.

S amples were shipped at ambient temperatures from the testing facility to the processing facility, where they wer e placed into frozen storage and remained frozen during shipping and storage prior to processing , preparation and analysis

. The maximum storage interval for samples was 44 6 days (14.7 months) for pre

- processing rice grain, 248 days (8.2 months) for polished rice and hulls, and 250 days (8.2 months) for bran from harvest/processing to extraction. Samples were ana lyzed

within 2

- 4 days of extraction. Processing took place within 185

- 197 days (6.1

- 6.5 months) of

harvest. S torage stability data are available indicat ing that residues of CGA179500 were stable

when stored frozen for up to 24 months in/on wheat grain

. No storage stability data are available for CGA179500 in processed commodities. The available storage stability data are adequate to support the storage conditions and durations for processed commodities of rice

Samples were analyzed for residues of trinexapac

- ethyl determined as CGA179500 using Syngenta Analytical Method GRM020.01A (with minor modifications), a high performance liquid chromatography meth od with tandem mass spectrometric detection (LC/MS/MS). The limit of quantitation (LOQ, determined as the lowest level of method validation, LL MV) was 0.01 ppm

. The method does not provide for conversion of residues of CGA179500 to parent equivalents; therefore quantifiable residues of CGA179500 were converted to parent equivalents by the st udy reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21). Acceptable concurrent recovery data were reported fo r rice grain (RAC) and polished grain samples at fortification levels of 0.01

- 1.5 p pm, for hulls at fortification levels

of 0.01

- 0.5 ppm, and for bran at fortification levels of 0.01

- 3.0 ppm, thus validating the method. Prior to analysis of samples, the method was v alidated on rice grain at two fortification levels of

CGA179500 ( 0.010 a nd 1.0 ppm )

. The fortification levels were adequate to b racket expected

residue levels.Trinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 3 of 8 

### In rice grain harvested at PHIs of 54

- 91 days f ollowing a single foliar broadcast application a 2.08 lb ai/gal EC formulation of trinexapac

- ethyl at an exaggerated rate of 0.134

- 0.135 lb ai/A (~3x the field application rate)

, residues of trinexapac

- ethyl (determined as CGA179500 ) were 0.11

- 0.63 ppm. Residues of CGA179500, converted to parent equivalents, were 0.11

- 1.04 ppm in polished rice, 0.025

- 0.37 pp m in hulls, and 0.63

- 2.81 ppm in bran.

The processing data indicate that residues of CGA179500 concentrate in polished rice (1.0

- 1.6x, median proce ssing factor 1.3x) and bran (4.4

- 5.8x, median processing factor 5.1x), but do not concentrate in hulls (0.2

- 0.6x, median processing factor 0.4x).

The observed processing factors calculated in this study were less than the maximum theoretical concentration factors of 7.7x for rice bran and 5.0x for rice hulls (based on separation of

compone nts; OCSPP 860.1520, T able 3).

STUDY DEFICIENCIES

Under the conditions and parameters used in the study, the processed commodity residue da ta for TCP are tentatively classified as scientifically a cceptable , pending the submission and evaluation of storage stability data for processed rice commodities.

I. MATERIALS AND METHOD S

A. MATERIALS

Table B. 7.7. 3 .1

- 1

. Nomenclature for Trinexapac

- ethyl and Metabolite of Interest

. Common name Trinexapac

- ethyl

Identity Ethyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate

CAS no. 95266

- 40

- 3
Company experimental name CGA163935
Other synonyms (if applicable) Not applicable

Metabolite CGA179500

Identity 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid

CAS no. 104273

- 73

- 6

Company experimental name See above

Other synonyms (if applicable) Trinexapac acidTrinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 4 of 8 Table B. 7.7. 3 .1

- 1

. Nomenclature for Trinexapac

- ethyl and Metabolite of Interest

.



### B. Study Design

1. Test Procedure

Location and detailed use pattern for the trial is provided in T able B. 7.7. 3 .1

- 2

.

T able B.7.7. 3 .1

- 2 . Study Use Pattern.

Location: City, State; Year (Trial ID) End

- use

Product 1 Method of Application/

Timing of Application Volume ( gal/A ) Rate per

Application ( lb ai/A ) Retreatment

Interval (days) Total Rate

( lb ai/A ) Surfactant/

Adjuvant 2

Washington, LA;

2012 ( TK0044924

- 1 0) 2.08 lb

ai/gal EC Foliar broadcast; BBCH

30

- 32 (panicle initiation or green ring stage) 10 0.13 4

-- 0.13 4 COC

Fisk, MO; 2012 (TK0044924

- 11) 2.08 lb

ai/gal EC Foliar broadcast; BBCH

30

- 32 (panicle initiation or green ring stage) 10 0.135

-- 0.135 NIS

1 End

- use product is A7725M, a 2.08 lb ai/gallon emulsifiable concentrat e (EC) formulation of trinexapac

- ethyl.

2 COC = crop oil concentrate. NIS = non

- ionic surfactant.



### Bulk samples of untreated and treated rice grain were harvested at maturity and transferred to the processing facility for preparation o f polis hed rice, hulls and bran

. Rice was processed using simulated industrial practices.

Sample Handling and Prepar ation

Single control and treated bulk samples of rice grain (~ 50 0 lb) w ere collected from each plot at maturity 54

- 91 days after application . T he bulk rice samples were delivered by site personnel or

s hipped at ambient temperature to the processing facility, G LP Technologies (Navasota, TX) within 3 days of harvest. Samples were frozen upon receipt at the processing facility , and processed fractions were stored frozen at ≤ 10 °F ( ≤

- 12  C ). Processing took place within 184

- 197 days (6.1

- 6.5 months) of harvest. Within 5

- 8 days a fter processing, RAC and processed fraction s were shipped via freezer truck to Syngenta Crop Protection, Inc. (Gr eensboro, NC), for sample preparation (grinding with dry ice). At Syngenta, samples were stored in a freezer at <

- 10 °C from receipt until removal for preparation, and between prepa ra tion and shipment for analysis. Subsamples were shipped frozen from Syngenta to North Coast Laboratories ( NCL; Arcata, CA ); the time from shipment to Syngenta to receipt at NCL was 84 d ays (2.8 months). Samples were
stored frozen ( ≤

– 20  C ) upon receipt at NCL prior to and after analysis.Trinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 5 of 8 

### Sample Processing

The processing procedure simulated commercial operations of rice production as closely as possible to generate the required fraction of rice grain (RAC), polished rice

, hulls , and bran , with

some va riations to commercial methods. Adequate descriptions of processing procedures were provided, including material balance summaries. A processing flowchart for rice , copied without

alteration from MRID 49282807 , is presented below in Figure B. 1.

FIGURE B. 1. Processing Flowchart for Polished Rice, Hulls, and Bran

.

2. Description of Analytical Procedures

Samples were analyzed for residues of trinexapac

- ethyl determined as CGA179500 by LC/MS/MS using Syngenta Analytical Method GRM020.01A “Analytical Method for the Determination of Residues of Trinexapac

- Ethyl as CGA179500 in Crops by LC

- MS/MS,” with minor

modifications

. This method was previously reviewed under DP# 378491 ( S. Piper, 11/23/2011 ) in conjunction a crop field trial submission for barley grain (48043702.der).

Briefly, samples were refluxed with acetonitrile (ACN)/1 N HCl (80:20

, v:v). An aliquot of the extract was applied to a C8 solid phase extraction (SPE) cartridge, and residues were eluted with 0.5% formic acid:ACN ( 70:30 v:v). The eluate was adjusted to volume for LC/MS/MSTrinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 6 of 8 

### analysis

. The method does not provide for convers ion of residues of CGA179500 to parent equivalents; therefore quantifiable residues of CGA179500 were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 2 24.21).

The LOQ (determined as the LLMV) was 0.01 ppm for CGA179500. The limit of detection (LOD) was not reported.

II. RESULTS AND DISCUSSION

Method performance was evaluated during method v alidation and by use of concurrent recovery samples . For method v alidation

, untreated samples of rice grain were fortified with CGA179500

at 0.01 and 1. 0 ppm, three samples each, and individual recoveries (and overall standard deviation)

were 97

- 122% (8.2%). For concurrent recovery, untreated samples of rice gr ain were fortified at

0.01 and 0.10 ppm
, six samples each, and ind ividual recoveries (and overall standard deviation)

were 78

- 123 % (12%). For concurrent recovery of processed commodities, one sample of each matrix (pre

- processed rice grain, polished rice, hulls and bran) was fortified with CGA179500 at
0.01 and 0.10 ppm (as well as 1.5 ppm for pre

- processed grain and polished rice, 0.5 ppm for hulls and 3.0 ppm for bran), and recoveries were 94

- 98%, 100

- 110%, 76

- 79%, and 72

- 98%, respectively, with an overall standard deviation of 12%. All recoveries were generally within the

a cceptable range of 70% to 120%.

T he method was consid ered valid for the analysis of trinexapac

- ethyl residues in rice matrices. The

fo rtification levels did bracket the measured residues. Concurrent recoveries were corrected fo r apparent residues in controls.

The detector response was linear (1x weighting), with coefficient of determination, r 2 

### ≥ 0.9946 within the range of 0.0 067

- 0.333 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 chromatograms contain ed only the analyte of interest, and peaks were symmetrical and well

defined. Apparent r esidues in controls were below the LOQ (<0.01 ppm ). The reported residue

values were not corrected for apparent residues in controls.

T able B.7.7. 3 .1

- 3 . Summary of Proce dural/Concurrent Recoveries of Trinexapac

- ethyl from Rice Matrices

. Matrix Analyte Fortification Level (ppm) Recoveries (%) Mean ± Std. Dev. (%)

Not applicable



### The pre

- processing rice grain (RAC) samples were stored frozen a maximum of 446 days (14.7 months) fr om harvest to extraction , and processed samples w ere stored frozen a maximum of 250 days (8.2 mon ths) from processing to extraction ( Table B.7.7.3.1

- 4). Samples were analyzed within 2

- 4 days of extractio n. Processing took place within 184

- 197 da ys (6.1

- 6.5 months) of harvest.

The available freezer storage stability data indicate that residues of trinexapac

- ethyl as CGA179500 were stable when stored frozen in wheat (grain ) for 2 4 months (45898903 .der ).Trinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 7 of 8 

### The available storage stability data are adequate to support the storage conditions and durations processed commodities of rice

.

T able B.7.7. 3 .1

- 4. Summary of Storage Conditions 1

. Matrix Storage Temperature ( °C ) Actual Storage

Duration (days /months ) Interval of Demonstrated Storage Stability

Rice grain (RAC) M aintain ed frozen at

processor ( ≤

- 12  C ), preparation facility ( <

- 10  C )

and analytical laboratory ( ≤

-

20  C ) 432

- 446 (14.2

- 14.7 ) R esidues of CGA179500 were stable when

stored frozen in wheat grain for up to 24 months 2

Polished rice 246

- 248(8.1

- 8.2) No storage stability data are available for CGA179500 in processed commodities. Hulls 246

- 248 (8.1

- 8.2)

Bran 248

- 250 (8.2)

1 Interval from harvest

/processing to extraction. S amples were analyzed within 2

- 4 days of extraction.

2 DP# 378491 ( S. Piper, 11/23/2011 ), 45898903 .der.



### Residues found in samples and processing factors are given in Table B.7.7. 3 .1

- 5

. In rice grain

harvested at PHIs of 54

- 91 days following a single foliar broadcast application a 2.08 lb ai /gal EC formulation of trinexapac

- ethyl at an exaggerated rate of 0.134

- 0.135 lb ai/A (~3x the field application rate) , residues of trinexapac

- ethyl (determined as CGA179500) were 0.11

- 0.63 ppm. Residues of CGA179500, converted to parent equivalents, were 0.11

- 1.04 ppm in polished rice,

0.025

- 0.37 ppm in hulls, and 0.63

- 2.81 ppm in bran.

The processing data indicate that residues of CGA179500 concentrate in polished rice (1.0

- 1.6x, median processing factor 1.3x) and bran (4. 4

- 5.8x, median processing facto r 5.1x), but do not concentrate in hulls (0.2

- 0.6x, median processing factor 0.4x).

Table B.7.7. 3 .1

- 5 . Resi due Data from Rice Processing Study with Trinexapac

- e thyl as CGA179500

Commodity Analyte Residues 1
(ppm) [Average] Processing Factor 2 Median Processing

Factor 3

Washington, LA; 2012 (TK0044924

- 10)

Rice grain ( RAC ) CGA179500 0. 8 7, 0.7 9 , 0.2 5 [0. 63 ]

-- -- Polished rice CGA179500 1.0 4 1.6 x 1.3 x

Hulls CGA179500 0.37 0.6 x 0.4 x

Bran CGA179500 2.8 1 4. 4 x 5. 1 x Fisk, MO; 2012 (TK0044924

- 11)
Rice grain ( RAC ) CGA179500 0. 1 1 , 0. 11 , 0. 11 [0. 11 ]

-- Polished rice CGA179500 0.11 1.0 x

Hulls CGA179500 0.025 0.2x

Bran CGA179500 0.63 5.8 x

1 The method determines residues of trinexapac

- ethyl as CGA179500. R esidues of CGA179500 were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21)

. 2 Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the RAC]. A separate processing factor is calculated for each processed commodity.

3 Median (and also mean in this case) of processing factors for both sites , determined for each matrix.Trinexapac

- ethyl [PC Code 112602]/ SyngentaCrop Protection, LLC

Processed Food/Feed

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: No t Available Page 8 of 8 

### III. CONCLUSIONS

The rice processing study is tentatively considered scientifically acceptable pending submission and evaluation of a storage stability study for processed commodities. In rice grain harvested at

PHIs of 54

- 91 days following a single foliar broadcast application a 2.08 lb ai/gal EC formulation of trinexapac

- ethyl at an exaggerated rate of 0.134

- 0.135 lb ai/A (~3x the field application rate) , residues of trinexapac

- ethyl (determined as CGA179500) were 0.11

- 0.63 ppm. Residues of CGA179500, converted to parent equivalents, were 0.11

- 1.04 ppm in polished rice,

0.025

- 0.37 ppm in hulls, and 0.63

- 2.81 ppm in bran.

The processing data indicate that residues of CGA179500 concentrate in polished rice (1.0

- 1.6x, median proce ssing factor 1.3x) and bran (4.4

- 5.8x, median processing factor 5.1x), but do not concentrate in hulls (0.2

- 0.6x, median processing factor 0.4x).

Adequate storage stability data are available to support sample s torage durations and conditions

for processed commodities of rice for CGA179500.

An acceptable method was used for residue quantitation.

Th e observed processing fa ctors calculated in this study were less than the maximum theoretical

concentration factors of 7.7x for rice bran and 5.0x for rice hulls (based on separation of components; OCSPP 860.1520, Table 3).

REFERENCES

DP# 378491 ( S. Piper, 11/23/2011 ); 48043702.der and 45898903 .derTrinexapac-ethyl [P C Cod e 112602] /S yngenta Crop Protection, LLC.

Ma g nitude of Re si due- Rice



### Primary Eva luat or

Approved by

B.7.6

B.7.6.1

B.7.6.1.1 

### Sumitra B ose Biswas, Chemist

Risk Assessment Branch VI (RA BVI)

th Effects Division (HED 7509P)

eila Piper, Se ·o r Ch emi st

RABVI

, HE D 750 9 P )

Residues Resulting from Supervised Trials (Annex IIA 6.3; Annex IllA 8.3)

Residues in Target Crops

Rice

Document 

### ID: MRID No. 49282807

PMRA No. Not Available Date: 10-MAR-2015

Date: IO- M AR

- 2015

Report: Smith, N. (2014) Trinexapac-Ethyl EC (A7725M)

- Magnitude of the

Re s idu es in or on Rice. Final Report GLP Study N umb e r: TK0044924,

N orth Co ast Study Number: 1 10.046

. Unpublished study prepared by Syn ge nta Crop Protection, LLC. 222 p. Guidelines: 

### EPA OCSPP Harmonized Te st Guideline 860.1500 Crop Field Trial s (August 199 6 )

P MRA Regulatory Directive DIR98-02 - R es idue Chemi stry Guideline s,
Section 9

- Crop F ield Trials

PMRA Regulatory Directive DIR2010-05

- Revisions to the Residue Chemistry Crop F i e ld Trial Requirements

OECD Guideline 509 Crop Field Trial (Se p te mber 2009)

GLP Compliance: 

### No deviations from regulatory requirement s were reported which wou ld

ha ve an impact on the validity of the study. Acceptability: 

### Th e study is considered scientifically acceptable. The acceptability of this study for regulator y purposes i s addressed in the forthcoming U.S. EPA

Re s idu e Chemistry Summary D oc ument

, DP # 424894

. Evaluator: 

### Sumitra Bose Biswas

Note : T his Data Eval u a ti o n Rec o rd (DE R) was ori g inall y prepared und er co ntract b y V ersa r
, Inc

. (685 0 Vcr sa r Center

, Springfield, VA 2215 1 ; s u bmitted 9/22/ 1 4 ). T he DER has been r eviewed by HED and revised to reflect cu rrent Office of

P esticide Pro grams (OPP) policies

.

EPA MRID # : 4928 2 807

Pa ge I of9

PMRA # of document: Not foundTrinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 2 of 9 

### EXECUTIVE SUMMARY

Syngenta Crop Protection, LLC has submitted fie ld trial data for trinexapac

- ethyl on rice from 14

field trials conducted in the United States during the 20 12 growing season in the North American

Free Trade Agreement (NAFTA) Growing Zone s 4 ( AR ; 4 trials , LA; 4 trials, MO; 1 trial), 5 (MO ; 1 trial), 6 (TX, 2 trials) and 10 (CA; 2 trial s)

. HED has concluded that 3 trials conducted in Zone 4 should be considered replicates . This decision is reflected in the total trial count
above

.

Each trial consisted of one untreated plot and one treated plot. Each treated plot received a single foliar broadcast spray application of the 2.08 lb ai/gal emulsifiable concentrate (E C)

formulation of trinexapac

- ethyl (Trinexapac

- Ethyl E C, A7725M ) made at BBCH 30

- 32 (panicle initiation or green ring stage) at 0. 041

- 0. 046 lb ai/A /application

. Applications were made u sing ground equipment in spray volumes of 2.4

- 10 gal/A. A nonionic surfactant (NIS) or crop oil concentrate (COC ) was included in the spray mixtures for all applications. Samples of rice grain

and straw were harvested at maturity at preharvest interval s (PHI s ) of 5 1

- 100 day s

. Rice straw is no longer considered a significant livestock feed item and is not further addres sed herein. At two
trial s (AR trial

- 09 and CA trial

- 15)

, additional sa mples were collected to monitor residue

decline 7 and14 days before and after normal crop harvest ; PHIs were 65, 72, 79, 85 and 94 days

for t rial

- 09 and 85, 92, 99, 106 and 113 days for trial

- 15

.

All samples were maintained frozen at the testing and sample preparation facilit ies

, during shipment to the analytical laboratory, and remained frozen until analysis

. The maximum storage

interval for rice grain samples between harvest and extraction was 365 days ( 12.0 months ).

S amples were analyzed within 1

- 3 days of extraction. S torage stability data are available

indicat ing that residues of CGA179500 were stable when stored frozen for up to 24 months in/on wheat grain

. These data are a dequate to support sample storage durations and conditions.

Samples were analyzed for residues of trinexapac

- ethyl determined as CGA179500 using Syngenta Analytical Method GRM020.01A (with minor modifications), a high performance liquid chromatography met hod with tandem mass spectrometric detection (LC/MS/MS). The limit of quantitation (LOQ, determined as the lowest level of method validation, LLMV) was 0.01 ppm. The method does not provide for conversion of residues of CGA179500 to parent equivalents; therefore quantifiable residues of CGA179500 were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21). Acceptable method validation and concurrent recovery data we re reported for rice grain fortified with CGA179500 at 0.01

- 1.0 ppm, thus validating the

method. The fortification levels were adequate to bracket expected residue levels.

In rice grain harvested at PHIs of 51

- 100 days following a single foliar broadcast application of the 2.08 lb ai/gal EC formulation of trinexapac

- ethyl at 0.041

- 0.046 lb ai/A, individual sample (and per

- trial average) residues of trinexapac

- ethyl (determined as CGA179500) were <0.01

- 0.270 ppm (<0.01

- 0.214 ppm).Trinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 3 of 9 

### I n one residue decline trial residues were variable, with the highest residues observed at the target PHI. In the second residue decline trial, residues were below the LOQ in/on all samples; therefore, residue decline could not be determined.

I. MATERIA LS AND METHODS

A. MATERIALS

Table B.7.6.1.1

- 1. Nomenclature for Trinexapac

- Ethyl and Metabolite of Interest.

Common name Trinexapac

- ethyl

Identity E thyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate

CAS no. 95266

- 40

- 3
Company experimental name CGA 163935
Other synonyms (if applicable) Not applicable

Metabolite CGA 179500
Identity 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid

CAS no. 104273

- 73

- 6
Company experimental name See above
Other synonyms (if applicable) Trinexapac acid



### B. Study Design

1. Test Procedure

Fourteen residue trials were conducted on rice reflecting foliar application at BBCH 30

- 32 with a

2 .0 8 lb ai/gal E C formulation during the 2012 growing season (Table B.7.6.1.1

- 2).

All trials, except for those listed in the table below, were separated by >20 miles and are therefore considered independent (568 _Criteria for Independence of Trials 04/23/2013 (EPA and PMRA)). The trials separated by <20 miles have been assessed for ind ependence as detailed in

the table below. HED has determined that three trials (05, 07 and 0 8 ) should be considered replicate trials. It is noted that since the study predates the guidance concerning field trail independence , the criteria specified in t he guidance was not strictly adhered to.Trinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 4 of 9 Independent Trial Determination 1

Trial Nos. Differences Decision

01, 06, and 09 Same location

Variet y : Roy J (mid

- season, long grain) vs. CL 261 (medium grain) vs. Wells (short

- season long

grain, large kernel size) All separate due to variety, different application dates (1

- 6 days), different spray volume (3

- 6 GPA), and/or different adjuvant.

04, 05, 07, 08, 10 Same location (05, 07, 08, 10) Variety : XL 729 (very early season, long grain, tall), CL 151 (very early season, long grain, semi

dwarf; 19.5K seed/lb), Cocodrie (very early, short season, long grain, semi

- dwarf, 20.6K seed/lb), Cypress (08 and 10; early, long

- grain, semi

- dwarf, 19.1K seed/lb) 04 separate due to variety (tall vs. semi

- dwarf) ; 10 separate due to different application date (20 days).

05, 07, 08: Replicates due to similar variety (all semi dwarf), same application dates, spray volume and same adjuvant.

11 and 12 Zone : 4 vs. 5 Separate due to Zone

13 and 14 Same location Variety : Presidio (early season, long grain, semi

dwarf) vs. Cheniere (very early season, long grain,

semi

- dwarf, hi yield).

No other differences in criteria Separates due to the varieties and different

a pplication date (8 days).

15 and 16 Same location and variety

No other differences in criteria

Residues : <0.01 vs. 0.074 ppm Separate due to different residues

1 All assessments are based on the replicate trial guidance presented in draft memo 568 _Criteria for Independence of T rials 04/23/2013 (EPA and PMRA) and have been approved by HED ; since the study predates the guidance, the criteria specified in the guidance was not strictly adhered to.

Table B.7.6.1.1

- 2. Trial Numbers and Geographical Locations.

Crop No.

Trials NAFTA Growing Zone Total

1 2 3 4 5 6 7 8 9 10 11 12

Rice Sub. 9 2 1 2 2 14

Req. 1 11/7 1/1 2/2 2/2 16/12

1 As per Table 5 of 860.1500 for rice, the second number reflects a 25% reduction in the number of field trials allowed for the crop as a representative commodity in support of a crop group/subgroup tolerance or when application results in no quantifiable

residues.

2 HED has determined that three trials conducted in Zone 4 are replicate trials.



### 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. Study Use Pattern.

Location: City,

State ; Year (Trial ID) End

- use

Product 1 Method of Application/ Timing of

Application Volume gal/A Rate per Application

lb ai/A Retreatment

Interval (days) Total

Rate

lb ai/A Surfactant/ Adjuvant 2

Proctor, AR; 2012 (TK0044924

- 01) 2.08 lb

ai/gal

EC 1. 1. Foliar broadcast; BBCH 30

- 32 3 0.045 NA 0.045 NIS

Pollard, AR; 2012 (TK0044924

- 02) 2.08 lb

ai/gal

EC 1. 1. Foliar broadcast; BBCH 30

- 32 5 0.045 NA 0.045 NIS

Cheneyville, LA;

2012 (TK0044924

- 03) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 9 0.046 NA 0.046 NISTrinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 5 of 9 Table B.7.6.1.1

- 3. Study Use Pattern.

Location: City,

State ; Year (Trial ID) End

- use

Product 1 Method of Application/ Timing of

Application Volume gal/A Rate per Application

lb ai/A Retreatment

Interval (days) Total

Rate

lb ai/A Surfactant/ Adjuvant 2

Ville Platte, LA;

2012 (TK0044924

- 04) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 10 0.046 NA 0.046 NIS

Washington, LA;

2012 (TK00044924

- 05) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 2.4 0.044 NA 0.044 NIS

Proctor, AR; 2012 (TK0044924

- 06) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 31

- 32 10 0.045 NA 0.045 NIS

Washington, LA;

2012 (TK0044924

- 07) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 3 0.044 NA 0.044 NIS

Washington, LA;

2012 (TK0044924

- 08) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 3 0.046 NA 0.046 NIS

Proctor, AR; 2012 (TK0044924

- 09) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 31

- 32 ) 10 0.045 NA 0.045 NIS

Washington, LA;

2012 (TK0044924

- 10) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 10 0.046 NA 0.046 COC

Fisk, MO; 2012 (TK0044924

- 11) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 10 0.045 NA 0.045 NIS

Fisk, MO; 2012 (TK0044924

- 12) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 10 0.045 NA 0.045 NIS

East Bernard, TX;

2012 (TK0044924

- 13) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 31

- 32 8 0.044 NA 0.044 COC

East Bernard, TX;

2012 (TK0044924

- 14) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 31

- 32 9 0.041 NA 0.041 COC

Porterville, CA;

2012 (TK0044924

- 15) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 9 0.045 NA 0.045 NIS

Porterville, CA;

2012 (TK0044924

- 16) 2.08 lb

ai/gal

EC 1. Foliar broadcast; BBCH 30

- 32 9 0.046 NA 0.046 NIS

1 End

- use product is A7725M, a 2.08 lb ai/gallon emulsifiable concentrate (EC) formulation of trinexapac

- ethyl.

2 COC= crop oil concentrate; NIS=non

- ionic surfactant

.



### Rice was grown and maintained according to typical agricultural practices . Irrigation was used

as needed

. Rainfall and temperature data were representative of the growing season. Actual temperatures were within average historical values for the residue study period, and t he actual rainfall average was w ithin the historical rainfall average

.Trinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 6 of 9 

### Sample Handling and Preparation

Single co ntrol and duplicate treated samples of rice grain were colle cted from each site at maturity at PHI s of 51

- 100 days. At two trials, additional samples were collected to monitor residue decline 7 and 14 days before and after normal crop harvest ; PHIs were 65, 72, 79, 85 and 94 days for trial

- 09 and 85, 92, 99, 106 and 113 days for trial

- 15

.

Samples were placed in froz en stor a ge at the field sites after collection

. All samples were shipped within 0

- 50 days by freezer truck or overnight courier (on dry ice ) to Syngenta Crop Protection, LLC ( Greensboro, NC ) for sample preparation (grinding in the presence of dry ice)

. At Syngenta, samples were stored for ~94

- 305 days frozen ( <

- 10 °C ) from receipt unt il removal for preparation, and between prepa ra tion and shipment for analysis. Subsamples were shipped

frozen by overnight courier from Syngenta to the analytical laboratory, North C o ast Laboratories
( NCL; Arcata, CA). Samples were stored frozen ( ≤

– 20  C ) upon receipt at NCL, prior to and after analysis.

2. Description of Analytical Procedures

Samples were analyzed for residues of trinexapac

- ethyl determined as CGA179500 by LC/MS/MS using Syngenta Analytical Method GRM020.01A “Analytical Method for the Determination of Residues of Trinexapac

- Ethyl as CGA179500 in Crops by LC

- MS/MS,” with minor

modifications. T his method was previously reviewed under DP# 378491 ( S. Piper, 11/23/2011 ) in conjunction a crop field trial submission for barley grain (4 8043702 .der)

.

Briefly, samples were refluxed with acetonitrile (ACN) /1 N HCl (80:20 v :v)

. An aliquot of the

e xtract w as applied to a C8 solid phase extraction ( SPE ) cartridge , an d residues were eluted with

0.5% formic acid :ACN ( 70:30 v : v ) . T he eluate was adjusted to volume for LC/MS/MS analysis

. The method does not provide for conversion of residues of CGA179500 to parent equivalents; therefore quantifiable residues of CGA179500 were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21).

The LOQ (determined as the LLMV) was 0.01 ppm for CGA179500. The limit of detection (LOD) was not reported.

II. RESULTS AND DISCUSSION

Method performance was evaluated during method verification and by use of concurrent recovery samples . For method validation , samples of untreated rice grain were fortified with

CGA179500 at 0.01 and 1.0 ppm each. Individual recoveries (and overall standard deviation)

were 97

- 122% (8.2%). For concurrent recovery, samples of rice grain were fortified at 0.01 and

0.10 ppm each. I nd ividual recoveries (and overall standard deviation) were 78

- 1 23 % (12%). All

recoveries were generally within the a cceptable range of 70

- 120% ; therefore the method was considered valid for the analysis of residues of trinexapac

- ethyl in rice grain

. The fo rtificationTrinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 7 of 9 

### levels bracketed the measured residues. Concurrent recoveries were corrected fo r apparent
residues in controls.

The detector response was linear (1/x weighting), with r 2 

### ≥ 0.999 6 for rice grain calibration curve

within the ran ge of 0.0067

- 0.333 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 chromatograms contained only the analyte of interest, and peaks were symmetrical and well

defined. Apparent r esidues in controls were below the LOQ (<0.01 ppm ). The reported residue

values were not corrected for apparent residues in controls.

Table B.7.6.1.1

- 4. Summary of Proce dura l/Con current Recoveries of Trinexapac

- ethyl from Rice

. Matrix Analyte Fortification

Level (ppm) Recoveries (%) Mean ± Std. Dev

. (%)

Not applicable. See above . (All mean recoveries were within acceptance criteria.)



### The field residue samples for rice grain w ere stored frozen a maximum of 365 days ( 12.0 months) from harvest to extraction (Table B.7.6.1.1

- 5). The available freezer storage stability

data indicate that residues of CGA179500 were stable when stored frozen in wheat grain for up

to 24 months (MRID45898903).

Table B.7.6.1.1

- 5. Summary of Storage Conditions.

Matrix Storage Temperature (°C) Actual Storage

Duration 1 Interval of Demonstrated Storage Stability

Rice Grain Maintained frozen in field, preparation facility ( <

- 10  C ) and analytical laboratory
( ≤

- 20  C ) 245

- 365 days

(8.1

- 12.0 months) R esidues of CGA179500 were stable when

stored frozen in wheat grain for up to 24

months

. 2

1 Interval from harvest to extraction

. Samples were analyzed within 1

- 3 days of extraction.

2 DP# 378491 ( S. Piper

, 11/23/2011. ); 45898903 .der.



### The results from the submitted field trials are presented in Tables B.7.6.1.1

- 6 and B.7.6.1.1

- 7

. In rice grain harvested at PHIs of 51

- 100 days following a single foliar broadcast application of the 2.08 lb ai/gal EC formulation of trinexapac

- ethyl made at 0.041

- 0.046 lb ai/A, individual sample (and per

- trial average) residues of t r inexapac

- ethyl (det ermined as CGA179500) were <0.01

- 0. 270 ppm (<0.01

- 0. 214 ppm)

.

In one residue decline trial residues were variable, with the highest residue s observed at the target PHI. In the second residue decline trial, residues were below the LOQ in/on all samples;

t herefore, residue decline could not be determined.

Table B.7.6.1.1

- 6. Residue Da ta from Rice Field Trials with Trinexapac

- Ethyl

. 1

Location: City, State;

Year 2 (Trial ID) Zone Rice Variety Matrix Rate

lb ai/A PHI 3

(days) Residues trinexapac

- ethyl 4 (ppm )

[Average]

Proctor, AR; 2012 (TK0044924

- 01) 4 Roy J Grain 0.045 74 0.069

, 0.059 [0.064]Trinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 8 of 9 Table B.7.6.1.1

- 6. Residue Da ta from Rice Field Trials with Trinexapac

- Ethyl

. 1

Location: City, State;

Year 2 (Trial ID) Zone Rice Variety Matrix Rate

lb ai/A PHI 3

(days) Residues trinexapac

- ethyl 4 (ppm )

[Average]

Pollard, AR; 2012 (TK0044924

- 02) 4 RiceTec XL 729 Grain 0.045 85 0.061

, 0.051 [0.056]
Cheneyville, LA; 2012 (TK0044924

- 03) 4 CL 111 Grain 0.046 53 0.060

, 0.056 [0.058]

Ville Platte, LA; 2012 (TK0044924

- 04) 4 XL 729 Grain 0.046 51 0.026

, 0.025 [0.025]
Washington, LA; 2012 (TK00044 9 24

- 05)

and Washington, LA; 2012 (TK0044924

- 07)

and Washington, LA; 2012 (TK0044924

- 08) 4 CL 151

Cocodrie

Cypress Grain 0.044

0.044

0.046 60

60

60 0.180

, 0.203

, 0.270

,

0.236

, 0.191

, 0.203 [0.214]

Proctor, AR; 2012 (TK0044924

- 06) 4 CL261 Grain 0 .045 68 0.024

, 0.024
[ 0.024]

Proctor, AR; 2012 (TK0044924

- 09) 4 Wells Grain 0.04 5 65 0.043

72 0.053

79 0.088, 0.075

[0.082]

85 0.061

94 0.070
Washington, LA; 2012 (TK0044924

- 10) 4 Cypress Grain 0.046 54 0.191, 0.203 [0.197]

Fisk, MO; 2012 (TK0044924

- 11) 4 RiceTec XP 753 Grain 0.045 91 0.038, 0.036 [0.037]

Fisk, MO; 2012 (TK0044924

- 12) 5 Francis Grain 0.045 85 0.037, 0.041 [0.039]

East Bernard, TX; 2012 (TK0044924

- 13) 6 Presidio Grain 0.044 90 0.113, 0.113 [0.113]

East Bernard, TX; 2012 (TK0044924

- 14) 6 Cheniere Grain 0.041 75 0.019, 0.019 [0.019]

Porterville, CA; 2012 (TK0044924

- 15) 10 Koshihikari Grain 0.045 85 ND

92 <0.01

99 <0.01, <0.01

[<0.01]

106 <0.01

113 <0.01

Porterville, CA; 2012 (TK0044924

- 16) 10 Koshihikari Grain 0.046 100 0.092, 0.0 83 [0.080]

1 A 2.08 lb ai/gal EC formulatioin (A7725M) was used.

2 HED has determined that Trials 05, 07, and 08 are replicate trials.

3 Target PHIs are bolded for decline trials.

4 ND = Not detected (no peak) as reported by the petitioner

. The method determines residues of trinexapac

- ethyl a s CGA179500. Residues of CGA179500 were converted to parent equivalents by the study reviewe r using a molecular weight conversion factor of 1.125 (MW trinexapac

- ethyl 252.26/MW trinexapac acid 224.21)

. Per trial averages were calculated by the study revie wer.Trinexapac

- ethyl [PC Code 112602] /Syngenta Crop Protection, LLC

.

Magnitude of Residue

- Rice

----------------------------------------------------------------------------------------------------------------------------- ---------------

EPA MRID #: 49282807

PMRA # of document: Not found Page 9 of 9 Table B.7.6.1.1

- 7. Summary of Residues from Rice Field Trials with Trinexapac

- Ethyl

. Crop Matrix Total

Application

Rate

lb ai/A PHI

(days) n 1 Residues (ppm Trinexapac

- ethyl )

Min. 2 Max. 2 LAFT 3 HAFT 3 Median 3 Mean 3 SD 3

Rice Grain 0.041

- 0.046 51

- 100 14 <0.01 0.270 <0.01 0.214 0.0 5 7 0.0 73 0.06 3

1 n = number of field trials.

2 Values based on total number of samples.

3 Values based on per

- trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values <LOQ are assumed to be at the LOQ ( 0.01 p pm for trinexapac

- ethyl as CGA179500 )

.



### III. CONCLUSIONS

The rice field trials are considered scientifi cally acceptable

. In rice grain harvested at PHIs of

51

- 100 days following a single foliar broadcast application of the 2.08 lb ai/gal EC formulation of trinexapac

- ethyl made at 0.041

- 0.046 lb ai/A, individual sample (and per

- trial average) residues of trinexapac

- ethyl (determined as CGA179500) were <0.01

- 0.270 ppm (<0.01

- 0.214 ppm).

In one residue decline trial residues were variable, with the highes t residues observed at the target PHI. In the second residue decline trial, residues were below the LOQ in/on all samples; therefore, residue decline could not be determined.

An acceptable method was used for residue quantitation , and adequate storage s tability data are available to support sample storage durations and conditions for trinexapac

- ethyl.

REFERENCES

DP# 378491 ( S. Piper

, 11/23/2011 ) ; 48043702.de r and 45898903.der

.