### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 1 of 70 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION



### MEMORANDUM

Date : September 30, 20 1 1

SUBJECT: Trinexapac

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

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

.

PC Code: 11 2602 DP Barcode s : 37 7921

Decision No.: 432768 and 433096 Registration No s

. : 100

- 727, 100

- 949 and 100

- 1241

Petition No s .: 0 F7 719 and 0F7720 Regulatory Action: Section 3 First Food Use
Registration s Risk Assessment Type: N A Case No.: N A

T XR No.: N A CAS No.: 95266

- 40

- 3

MRID No.: 48043701

- 09, 47101606,

47101603, 48043601

- 04, 45898901

- 09,

46809305

- 06 40 CFR: N A

FROM: Sheila Piper, Chemist

Risk Assessment Branch VI

Health Effects Division (7509P)

THROUGH: ChemSAC/HED (7509P)

and

Felecia Fort, Branch Chief

Risk Assessment Branch VI

Health Effects Division (7509P)

TO: Bethany Benbow, Risk Manager Reviewer

Kathryn Montague, Risk Manager

Herbicide Branch

Registration Division (7505P)

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 2 of 70 MRID Summary Table

MRID No. Study Type Comments

48043704 860. 13 00 (hen metabolism study) New DER; 4 8043704.der (860.13 00)

48043705 860. 1300 (goat metabolism study) New DER; 4 8043705.der (860.1300)

48043702 860.1340 (crop analytical method) New DER; 48043702.der , i ncluding 48043703 ( 860.1340)

48043703 860.1340 (ILV for crop method)

48043706 860.1340 (animal method radiovalidation) New DER; 48043706.der, including 48043707 and 48043708

(860.1340) 48043707 860.1340 (animal analytical method)

48043708 860.1340 (ILV for animal method)

47101601 860.1380 (grass storage stability) New DER; 4 7101601.der (860.1380)

47101603 860.1480 (dairy cattle feeding study) New DER; 4 7101603.der (860.1480)

48043604 860.1480 (poultry feeding study) New DER; 4 8043604.der (860.1480)

48043603 860.1500 (barley field trials)

860.1520 (barley processing study) New DER; 4 8043603.der 1 (860.1500)

New DER; 4 8043603.der 2 (860.1520)

48043601 860.1500 (wheat field trials)

860.1520 (wheat processing study) New DER; 4 8043601 .der1 (860.1500)

New DER; 4 8043601.der 2 (860.1520)

48043602 860.1500 (sugarcane field trials)

860.1520 (sugarcane processing study) New DER; 4 8043602.der 1 (860.1500)

New DER; 4 8043602.der 2 (860 .1520)

48043701 860.1500 (grass field trials) New DER; 4 8043701.der (860.1500)

48043709 860.1850 (confined rotational crop study) New DER; 4 8043709.der (860.1850)

45898901 860.1500 (grass grown for seed ; 2001 ) New DER; 45898901.der (860.1500)

45898902 860.1300 ( grass metabolism study) New DER; 45898902.der (860.1300)

45898903 860.1380 (wheat and rapeseed storage

stability) New DER; 45898903.der (860.1380)

45898904 860.1300 (wheat metabolism study) New DER; 45898904.der (860.1300)

45898905 860.1300 (goat metabolism study) New DER; 45898905.der (860.1300)

45898906 860.1340 (independent laboratory

validation) New DER; 45898906.der (860.1340)

45898907 860.1340 (residue analytical method) New DER; 45898907.der (860.1340)

45898908 860.1360 ( confined accumulation

rotational crops ) New DER; 45898908.der (860.1360)

45898909 860.185 0 (residue analytical method) New DER; 45898909.der (860.1850)

46809305 860.1500 (grass grown for seed ; 2004 ) New DER; 46809305.der (860.1500)

46809306 860.1300 (rice metabolism study) New DER; 46809306.der (860.1300)



### This document was originally prepared under contract by Versar, Inc. (6850 Versar Center,
Springfield, VA 22151; submitted 12/14/10). The DER has been reviewed by the Health Effects

Division (HED) and revised to reflect current Office of Pesticide Programs (OPP) policies.

Executive Summary

Trinexapac

- ethyl is a plant growth regulator currently registered to Syngenta Crop Protection

, Inc. for use on perennial ryegrass grown for seed in the Pacific Northwest. For the new uses that

are the subject of these petition s , trinexapac

- ethyl is formulated as both a 1 lb/gal emulsifiable
concentrate (EC, 12% ai) under the trade name PalisadeTM EC (EPA Reg. No . 100

- 949) and as a

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 3 of 70 2 lb/gal EC ( 25.5%, Palisade ® 

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

- 1241 ).

Previously (PP#3F6571 ; DP#s 328850, 328853, 328898 ), Syngenta proposed registration of the
1 lb/gal EC product on grasses to include grasses gro wn for se ed throughout the U.S. However,

a number of deficiencies were noted in the petition that precluded establishing permanent

tolerances for trinexapac

- ethyl in grass and livestock commodities and resulted in a regionally
restricted registration on ryegrass

.

In the current petition (PP#0F7719), Syngenta has re

- proposed use of trinexapac

- ethyl in/on
grasses grown for seed throughout the U.S. and proposes registration of both the 1 and 2 lb/gal
EC products for this use

. The proposed use directions would allow for a single or split

application of trinexapac

- ethyl to grasses grown for seed during stem elongation and floral
development, at a maximum application rate of 0.5 lb ai/A. The registrant has proposed a

maximum seas onal rate of 0.5 lb ai/A, a 35

- day preharvest interval (PHI) for ma ture grass, and a

49

- day pre

- grazing interval (PG I ) for regrowth of forage and hay following harvest.

Additionally, in a separate petition ( PP#0F7720 ) , Syngenta has also proposed new uses and

tolerances to support the use of the 1 and 2 lb /gal EC products o n cereal grains ( barley, oats,

triticale, and wheat ) and sugarcane

. The registrant proposes to allow a maximum seasonal rate

of 0. 11 lb ai/A and a 4 5

- day PHI for cereal grains and a maxi mum seasonal rate of 0. 31 lb ai/A

and a 28

- day PHI for sugarcane.

Prior to receipt of these new petitions, n o tolerances ha d been established for trinexapac

- ethyl

residues on any food or feed commodities in the U.S. Trinexapac

- ethyl is the ethyl ester of the
carboxylic acid trinexapac. U nder PP# 0F7719

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

- ethyl, 4

- (cyclopropyl

- α

- hydroxy

- methylene)

- 3,5

- dioxo

- cyclohexanecarboxylic acid ethylester expressed as its primary metabolite CGA

179500, 4

- (cyclopropyl

- α

- hydroxy

- methylene)

- 3,5

- dioxo

- cyclohexanecarboxylic acid in/on
grass and livestock commodities at the following levels :

Grass, forage

................................ .............................. 1.6 ppm Grass, hay

................................ ................................ ... 3

. 5 ppm Grass, seed screening

................................ ............... 45.0 ppm Grass, straw

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

. 0 ppm Cattle, fat

................................ ................................ .... 0. 05 ppm Cattle, meat

................................ ................................ 0.05 ppm Cattle, meat byproducts

................................ ............. 0

. 05 ppm Goat, fat

................................ ................................ ...... 0

. 05 ppm Goat, meat

................................ ................................ .. 0.05 ppm Goat, meat byproducts

................................ ............... 0

. 05 ppm Horse, fat

................................ ................................ .... 0

. 05 ppm
Horse, meat

................................ ................................ 0.05 ppm Horse, meat byproducts

................................ ............. 0

. 05 ppm Sheep, fat

................................ ................................ .... 0

. 05 ppm Sheep, meat

................................ ................................ 0.05 ppm Sheep, meat byproducts

................................ ............. 0

. 05 ppm

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 4 of 70 In a separate petition (PP#0F7720), Syngenta is proposing the establishment of permanent

tolerances for residues of trinexapac

- ethyl, 4

- (cyclopropyl

- α

- hydroxy

- methylene)

- 3,5

- dioxo

cyclohexanecarboxylic acid ethylester expressed as its primary metabolite CGA

- 179500

, 4

- (cyclopropyl

- α

- hydroxy

- methylene)

- 3,5

- dioxo

- cyclohexanecarboxylic acid in/on barley, oat,

wheat, sugarcane, and livestock commodities at the following levels :

Barley, grain

................................ ............................... 1.60 ppm Barley, hay

................................ ................................ . 0. 7 0 ppm Barley, straw

................................ .............................. 0. 35 ppm Cattle, kidney

................................ ............................. 0. 05 ppm Sugarcane, c ane

................................ ......................... 0. 80 ppm Hog, kidney

................................ ................................ 0.05 ppm Oat, forage

................................ ................................ .. 1

. 00 ppm Oat, grain

................................ ................................ .... 4

. 10 ppm Oat, hay

................................ ................................ ...... 1

. 30 ppm Oat, straw

................................ ................................ ... 0.70 ppm Wheat, forage

................................ ............................. 1

. 00 ppm Wheat, grain

................................ ............................... 4

. 1 0 ppm Wheat, hay

................................ ................................ .. 1

. 3 0 ppm Wheat, straw

................................ ............................... 0.7 0 ppm

The nature of trinexapac

- ethyl residues in grass , cereal grain and sugarcane c ommodities and

ruminant is understood based on the available grass, rice, poultry and goat metabolism studies

. The residues of concern in plants and livestock fo r tolerance establishment and risk assessment
purposes include free and conjugated residues of both parent and its acid metabolite, trinexapac

( Residues of Concern Knowledgebase Subcommittee (ROCKS), D390121, 7/ 1 2 /11)

.

The petitioner has provided a data collection method, GRM020.01A, for the determination of

residues of trinexapac acid (CGA179500) in crop matrices using high performance liquid
chromatography with triple

- quadr u p o le mass spectrometric (LC

- MS/MS) analysis. This method

is a modified version of Syngenta Analytical Method 110

- 01 for the determination of residues of

CGA179500 using HPLC

- MS/MS instrumentation. The new method includes a strong acid
hydrolysis/extraction procedure to release both “free” and “conjugated” residues of CGA179500

from field grown grass commodities to fulfill the data deficiencies noted in a previous petition

review (DP#s 328858, 328853, and 323398 ) . For grass and crops, the limit of quantification
(LOQ) is 0.01 ppm. Based on recovery data submitted, Method GRM020.01A is adequate for

data

- collection for residues of trinexapac acid (CGA179500) in/on plants. The requirements for

r adiovalidation data are fulfilled and an adequate independent laboratory validation ( ILV ) study

has been submitted.

The petitioner has also provided a data collection method, REM 137.14, for the determination of
residues of trinexapac acid in livestock matrices using high performance liquid chromatography
with triple quadrupole mass spectrometry (LC

- MS/MS) analysis. The LOQ was established as

0.01 ppm for egg, kidney, liver, muscle, and fat and 0.005 ppm for milk. Based on recovery data

submitted, Analytical Method REM 137.14 is adequate for data

- collection for residues of

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 5 of 70 trinexapac acid (CGA179500) in livestock matrice s. The requirements for r adiovalidation data
are fulfilled and an adequate ILV study has been submitted.

In the fie ld trial and processing studies submitted, residues of trinexapac

- ethyl as CGA179500
were determined using an adequate LC

- MS/MS method ( GRM020.01A ). In the feeding studies

submitted, residues of trinexapac

- ethyl as CGA179500 were determined using adequate LC

MS/MS method ( REM 137.14 ). The method s w ere adequately validated both prior to and in
conjunction with the analysis of the field tr ial , processing, and feeding study samples. T he

validated LOQ was 0.01 ppm in each matrix tested.

Adequate multiresidue method data for trinexapac

- ethyl and trinexapac were previously

submitted. These data indicate FDA multi

- residue methods are not suit able for determining
residues of trinexapac

- ethyl and trinexapac in plant commodities. The data will be forwarded to

the U.S. FDA for further evaluation.

A storage stability study submitted in conjunction with the previous petition (PP#3F6571; DP#s

328850, 328853, 328898 ) was deemed adequate . Trinexapac residues were stabl e for 24 months

for wheat grain, 12 mont hs for wheat straw , and up to 9 months for grass

. For samples of straw
(dry forage) and oilseeds stored for up to 24 months , correction factors of 1.33x and 1.18x
should be applied when calculating residues. The available storage stability data for wheat

(grain and straw) are adequate to support the storage durations and conditions of grass, barley,
wheat, and sugarcane RAC s amples in the current submissions. In addition, the petitioner
submitted the results of a storage stability study with CGA

- 163935 (trinexapac

- ethyl) and CGA

179500 (trinexapac) in grass (clippings and thatch + sod)

.

Since actual storage durations of th e study samples from the dairy cattle feeding study were not

provided, it is uncertain if the submitted concurrent storage stability data support the storage
durations for study samples. Information on storage durations for the study samples is needed. If
study samples were stored longer than the demonstrated storage stability interval, additional

storage stability data demonstrating the stability of CGA 179500 will be required to cover the
storage durations for the study samples. The concurrent storage s tability d ata support the storage

conditions and durations of CGA179500 for the poultry livestock feeding study samples.

The livestock feedstuffs included in the current petitions are grass (forage, hay, and silage),
barley (hay, straw, and grain), wheat (forage, hay, straw, grain, and milled byproducts), and

sugarcane molasses. Adequate dairy cow and poultry feeding studies have been submitted.
These studies are acceptable for determining tolerance levels for livestock commodities. Based

on the submitt ed data, HED has concluded that tolerances for residues of trinexa pac

- ethyl,

determined as trinexapac (CGA179500)

, are required for certain livestock commodities.

The submitted magnitude of the residue data for the RACs of the following crops are adequate

pending tolerance adjustments: barley, wheat, sugarcane, and grass grown for seed. The
conducted trials support the above crops and reflect the proposed use patterns.

No residue data were submitted to support the proposed uses on oats. The submitted data for
wheat may be translated to oats. The proposed uses on all types of cereal grains are identical.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 6 of 70 Residues of residues of CGA179500 concentrated in pearled barley ( average processing factor of

1.2 x), barley bran ( average processing factor of 1.8x ), sugarcane molasses (average processing

factor of 5.8x), wheat bran (average processing factor of 1.8x) and wheat germ (average
processing factor of 1.1x). Residues also concentrated in wheat middling, with an average

processing factor of 3.2x, based on three trials with processing factors of 0.34

- 0.55x and one trial
with a processing factor of 11.3x.

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

- ethyl in or on any food or feed crops. Howe ver, a variety of European
countries, as well as Argentina, Brazil, Japan, Korea, and Australia have established or proposed

MRLs for trinexapac

- ethyl on cereal grains (0.02

- 0.5 mg/kg), cereal grain forages and fodders

(0.2

- 3 mg/k g), rapeseed (1

- 2 mg/kg), sugar cane (0.05

- 0.1 mg/kg), sugar forage and fodder (1
mg/kg), meat (0.02 m g/kg), and/or milk (0.1

- 0.005 mg/kg).

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for trinexapac

- ethyl . P rovided the
deficiencies identified below and further provided there are no risk issues identified in the
forthcoming human health risk assessment

, there are no residue chemistry issues that would

preclude granting the requested registration and establishing the following tolerance s.

To support the new uses that are the subject of these petitions, a new entry should be made in the

40 CFR for the active ingredient trinexapac

- ethyl. The recommended tolerance expres sion and

residue levels are outlined below:

Tolerances are established for residues of the plant growth regulator trinexpac

- ethyl, including
its metabolites and degradates, in or on the commodities listed below. Compliance with the

tolerance levels specif

ied below is to be d etermined by measuring both trinexapac

- ethyl, ethyl 4

- (cyc lopropylhydroxymethylene)

- 3, 5

- dioxocyclohexanecarboxylate and the associated metabolite
trinexpac, 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid , calculated as the stoichiometric equivalent of trinexapac

- ethyl

.

Barley, grain

................................ ............................... 2.0 ppm Barley, hay

................................ ................................ . 0. 8 ppm Barley, straw

................................ .............................. 0.4 ppm Barley, bran

................................ ................................ 2. 5 ppm Grass, forage

................................ .............................. 1. 5 ppm Grass, hay

................................ ................................ ... 4.0 ppm Grass, seed screening

.................................... 4 0 ppm Grass, straw

............................................... 1 0 ppm Oat, forage

................................ ................................ .. 1. 0 ppm Oat, grain

................................ ................................ .... 4

. 0 ppm Oat, hay

................................ ................................ ...... 1

. 5 ppm Oat, straw

................................ ................................ ... 0.9 ppm Sugarcane, cane

................................ ......................... 0.8 ppm

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 7 of 70 Sugarcane, molasses

................................ .................. 2.5 ppm Wheat, forage

................................ ............................. 1

. 0 ppm Wheat, grain

................................ ............................... 4

. 0 ppm Wheat, hay

................................ ................................ .. 1

. 5 ppm Wheat, straw

................................ ............................... 0.9 ppm Wheat, bran

................................ ................................ 6. 0 ppm Wheat, middlings

......................................... 10. 5 ppm Cattle, fat

................................ ................................ .... 0.0 2 ppm Cattle, meat

................................ ................................ 0.0 2 ppm Cattle, meat byproducts

................................ ............. 0.0 4 ppm Goat, fat

................................ ................................ ...... 0. 02 ppm Goat, meat

................................ ................................ .. 0.02 ppm Goat, meat byproducts

................................ ............... 0.0 4 ppm Horse, fat

................................ ................................ .... 0. 02 ppm
Horse, meat

................................ ................................ 0.02 ppm Horse, meat byprodu cts

................................ ............. 0.0 4 ppm Sheep, fat

................................ ................................ .... 0. 02 ppm Sheep, meat

................................ ................................ 0.02 ppm Sheep, meat byproducts

................................ ............. 0.0 4 ppm Hog, fat

................................ ................................ ....... 0.02 ppm

Hog, meat

................................ ................................ ... 0.02 ppm
Hog meat byproducts

................................ ................. 0.0 3 ppm

860.13 8 0 Storage Stability

Since actual storage durations of the study samples from the dairy cattle feeding study

were not pr ovided, it is uncertain if the submitted concurrent storage stability data
support the storage durations for study samples. Information on storage durations for the

study samples is needed. If study samples were stored longer than the demonstrated

storage stability interval, additional storage stability data demonstrating the stability of
CGA 179500 will be required to cover the storage durations for the study samples.

860.1550 Proposed Tolerances

The petitioner is required to submit a revised Section F to: (i) propose tolerances for

barley bran

, sugarcane, molasses , wheat bran, and wheat middlings ; and (ii) reflect the
revised tolerances and commodity definitions presented in Table 22

.

Background

Trinexapac

- ethyl is a new plant growth regulator being proposed by Syngenta Crop Protection
for use on grasses grown for seed , sugarcane and cereal grain s throughout the U.S. Trinexapac

ethyl inhibits internodal elongation and growth in cereal grains, grasses and several

dicotyledonous species. It is registered in numerous European countries and several Asian and

Latin American countries for uses on cereal grains and sugarcane. In the U.S., both 1 and 2
lb/gal EC formulation s of trinexapac

- ethyl are currently registered for use on perennial ryegrass

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 8 of 70 grown for seed in Idaho, Oregon and Washington. No tolerances have been established for
trinexapac

- ethyl residues on any food or feed commodities.

The nomenclature and physicochemical properties of trinexapac

- ethyl are pr esented 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

- 6

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 9 of 70 Table 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



### 860.1200 Directions for Use

The formulation s being proposed by Syngenta for use on cereal grains ( barley, oats, triticale, and

wheat ) , sugarcane, and grasses grown for seed are the 1 lb/gal EC (12% ai, Palisade TM EC; EPA

Reg. No. 100

- 949) and the 2 lb/gal EC ( 25.5%, Palisade ® 2EC; EP A Reg. No. 100

- 1241 ). Both

EC formulation s are currently registered for use on perennial ryeg rass in the Pacific Northwest.
The petitioner did not provide specimen label s for the two end

- use products ; t he proposed use

directions were obtained from Section B of the petitions (Table 3).

T able 3 . Summary of Directions for Use of Trinexapac

- Ethyl

.

Applic. Timing,
Type, and Equip. Form.

[EPA Reg.

No.] Applic.

Rate

(lb ai/A) Max. No.

Applic.

per

Season Max.

Seasonal
Applic. Rate

(lb ai/A) RTI

(days) PHI
(days) Use Directions and Limitations

Grasses grown for seed 1

Broadcast foliar
application 1.0 lb/gal

EC

[100

- 949]

2.0 lb/gal

EC

[100

- 1241] 0. 0 9

-

0.50 1

0.5 7

- 10 2 35 For single application, apply
before or during stem
elongation stage of
development (Zadoks 30

- 37

or Feekes 5

- 8). For split
application, apply the first
application before or during
stem elongation stage of
development (Zadok 30

- 37

or Feekes 5

- 8) followed by a
second application 7

- 10 days

later

. Do not al low livestock
to graze or cut for feed
within 49 days of the last
application. Other crops
may be planted 30 days after 0.05

- 0.25 2

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 10 of 70 T able 3 . Summary of Directions for Use of Trinexapac

- Ethyl

.

Applic. Timing,
Type, and Equip. Form.

[EPA Reg.

No.] Applic.

Rate
(lb ai/A) Max. No.

Applic.

per

Season Max.

Seasonal
Applic. Rate

(lb ai/A) RTI

(days) PHI
(days) Use Directions and Limitations

the last application. Apply

in a minimum of 5 and 10
gal/A using aerial and
ground equipment,
respectively.

Cereal Grains including Wheat (Winter, Spring, and Durum), Barley (Winter and Spring), Oats, and

Triticale

Broadcast foliar
application

1.0 lb/gal

EC

[100

- 949]

2.0 lb/gal

EC

[100

- 1241] 0.09

-

0.11 1

0.11 NA 3

45 Apply at Feekes 5 (leaf
sheath strongly erect) to
Feekes growth stage 8
(ligule of flag leaf visible).
Apply before the flag leaf
sheath extends. For barley,
it is recommended to apply

before the third node. For
improved root development,
apply at Feekes 3

- 5 (tillers

formed to leaf sheath

str ongly erect). Apply in a
minimum of 20 gal/A.

Broadcast foliar
application 0.05 2 NS 3 For split applications, apply

at Feekes 4

- 5 (leaf sheaths
lengthening to leaf sheath
strongly erect) and then
again at Feekes 7 (second
node visible). For barley,
apply at Feekes 6

- 7 (1 st to

2 nd nodes visible) and then
again at 8 (flag leaf just
visible). Apply in a
minimum of 20 gal/A.

Sugarcane

Broadcast foliar
application for
ripening

1.0 lb/gal

EC

[100

- 949]

2.0 lb/gal

EC

[100

- 1241] 0.18

-

0.31 1

0.31 NA 3 28 Application may be made

28

- 60 days prior to harvest
to increase sugar content

and/or extend harvest

window.

Broadcast foliar
application for

internode
shortening for
seed piece
production 0.06

- 0.2 2 NS 3 NS For split applications, make
first application when 6 fully
developed full size leaves
have appeared. Note the

bottom leaf should be
feeding internodes above the

soil surface. Make a second
application when 6
additional fully developed

full size leaves h ave appeared.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 11 of 70 1 PP#0F7719, Section B for grasses grown for seed specifies that other crops may be planted 30 days after the last
application.

2 For split applications, the second application should be made 7

- 10 days following the first application.

3 NA = Not Applicable; NS = Not Specified



### HED Conclusions

The label directions from Section B of the petitions are adequate to allow evaluation of the
residue data relative to the proposed use . Section B of the grass petition (PP#0F7719) specifies

that “other crops may be planted 30 days after the last application ” and this should remain on the

label.

860.1300 Nature of the Residue

– Plants

DER Reference s : 45898902.der (grass) ; 45898904.der (spring wheat); 46809306.der (rice)



### Grass. In the grass met abolism study, [1,2,6

- 14 

### C

- cyclohexyl]tri n exapac

- ethyl (98.1%

radiochemical purity) was applied to field plots of tall fescue grass approximate ly 45 days prior
to normal maturity, as a single broadcast foliar application at 0.5 lb ai/A (560 g ai/ha ; 1x rate ).

[ 14 

### C] trinexapac

- ethyl was formulated as an EC and diluted with water for application. A sample

of late

- season forage was collected 22 DAT, and the mature grass was cut at 46 DAT and

allowed to field

- dry for 13 days prior to separating the hay into str aw, seeds, and seed
screenings. The treated plots were allowed to regrow, and samples of forage were collected at 56

days following harvest, or 102 DAT.

Total radioactive residues (TRR) were 2.03 ppm in late

- season forage harvested at 22 DAT, and

4.78, 5.45 and 7.13 ppm in/on straw, seeds

, and seed screenings, respectively, harvested at
maturity (46 DAT). Following regrowth after harvest, the TRR was 0.054 ppm in forage
collected at 102 DAT. The metabolite profile was qualitatively and quantitatively s imilar in each

grass matrix. Parent was not detected in any matrix, and the major 14 

### C

- residues were identified
as trinexapac (10.2

- 21.8% TRR) and CGA

- 275537 (9.3

- 15.5% TRR). The other identified
components included Metabolites A (1.9

- 10.1% TRR), Metaboli te B (2.7

- 9.2% TRR) and

Metabolite C (6.6

- 11.0% TRR).

Table 4. Characterization and Identification of Radioactive Residues in Grass Matrices Following a

Single Foliar Application of [1,2,6

- 14 C] Cyclohexyl

- CGA

- 163935 at 0.50 lb ai/A

.

Compound /Fraction 1 Forage (22 DAT) Straw Seeds Seed screenings Forage (regrowth)

TRR = 2.028 ppm TRR = 4.777 ppm TRR = 5.452 ppm TRR = 7.130 ppm TRR = 0.054 ppm

%TRR ppm 2 %TRR ppm 2 %TRR ppm 2 %TRR ppm 2 %TRR ppm 2

CGA

- 163935 ND

-- ND

-- ND

-- ND

-- ND

-- CGA 179500 15.84 3 0.321 21.79 3 1.041 13.69 0.747 12.13 0.865 10.23 0.006

CGA

- 275537 11.14 0.226 13.03 0.622 14.54 0.794 15.46 1.103 9.34 0.005

Metabolite A 7.26 0.147 10.09 0.482 1.90 0.104 3.59 0.256 4.40 0.002

Metabolite B 7.83 0.159 5.22 0.25 7.38 0.403 9.18 0.655 2.72 0.001

Metabolite C 9.16 0.186 8.38 0.400 8.56 0.466 10.99 0.784 6.61 0.004

Total identified 51.23 1.039 58.51 2.795 46.07 2.514 51.35 3.663 33.3 0.018

Minor unknowns 4

Region 1 7.75 0.157 5.60 0.267 6.90 0.376 6.75 0.481 10.04 0.005

Region 2 10.15 0.206 4.07 0.195 4.32 0.236 5.43 0.387 ND

-- Region 3 9.72 0.197 10.63 0.508 7.05 0.385 8.50 0.606 2.69 0.001

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 12 of 70 Table 4. Characterization and Identification of Radioactive Residues in Grass Matrices Following a

Single Foliar Application of [1,2,6

- 14 C] Cyclohexyl

- CGA

- 163935 at 0.50 lb ai/A

.

Compound /Fraction 1 Forage (22 DAT) Straw Seeds Seed screenings Forage (regrowth)

TRR = 2.028 ppm TRR = 4.777 ppm TRR = 5.452 ppm TRR = 7.130 ppm TRR = 0.054 ppm

%TRR ppm 2 %TRR ppm 2 %TRR ppm 2 %TRR ppm 2 %TRR ppm 2

Region 4 3.98 0.080 3.45 0.165 15.54 5 0.848 16.29 5 1.161 6.85 0.004

Region 5 2.29 0.046 5.19 0.248 7.01 0.382 6.68 0.476 2.66 0.001

Region 6 5.67 0.115 5.99 0.286 6.48 0.354 4.39 0.313 2.63 0.001

Total Unknowns 39.56 0.801 34.93 1.669 47.30 2.581 48.04 3.424 24.87 0.012

Total characterized 90.79 1.840 93.44 4.464 93.37 5.095 99.39 7.087 58.17 0.030

Total extract ed 5 86.38 1.752 88.76 4.240 89.96 4.906 93.30 6.655 55.54 0.030

Unextract ed 6 9.38 0.190 9.83 0.700 9.21 0.501 5.08 0.360 34.83 0.019

Accountability 7 95.8 98.6 99.2 98.4 90.4

1 Total residues of CGA

- 179500 and CGA

- 275537 in forage and straw include 14 C

- residues of these compounds released by

enzymatic hydrolysis.

2 Expressed in [ 14 C] parent equivalents.

3 The majority (64

- 66%) of the CGA

- 179500 recovered from forage and straw was released by enzymatic hydrolysis.

4 In any individual solvent fraction, the minor unknowns each accounted for ≤9.7% of the TRR or <0.01 ppm. For forage (22

DAT) and straw, totals for each unknown used levels of each unknown following enzymatic hydrolysis.

5 Based on data from forage and straw, these unknown fractions contain conjugates of CGA

- 179500.

6 Total residues released by solvent extraction at room temperature and by reflux/microwave extraction.

7 Residues remaining after exhaustive solvent extractions.

8 Accountability = (Total extract ed + Total unextract ed )/(TRR from combustion analysis; see TABLE C.2.1) * 100.



### Rice. In the rice metabolism study, [1,2,6

- 14 

### C

- c yclohexyl ]trinexapac

- ethyl (>95% radiochemical

purity) was applied to rice as a single broadcast foliar application at either 40 g ai/ha (0.036 lb

ai/A, 1x rate) during stem elongation or at 160 g ai/ha (0.14 lb ai/A, 4x rate) during panicle
emergence. The rice was grown in a greenhouse using simulated paddy conditions, and the 14 

### C

test substance was formulated as a microemulsion and diluted with water for application. For the
1x application, samples of foliage and paddy water were collected at one hour post

- treatment and
at 7 and 21 DAT. Samples of straw, grain and husks were collected at maturity (82 DAT). For

the 4x application, samples of straw, grain , and husks were also collected at maturity (60 DAT).

For rice treated at the 1x rate, TRR in/on immature foliage were 0.565 ppm at 0 DAT and

declined to 0.066 ppm by 21 DAT

. Radioactivity in the paddy water was 0.020 ppm at 0 DAT

and declined to <0.00 1 ppm by 21 DAT. By crop maturity, TRR were 0.161 ppm in/on straw,
0.168 ppm in/on husks, and 0.085 ppm in/on grain. For 4x

- treated rice, TRR at maturity (60

DAT) were 1.58 ppm in/on straw, 2.22 ppm in/on husks, and 1.07 ppm in/on grain. Samples

were st ored at

- 18oC, and the initial qualitative and quantitative analyses were completed within
2.5 months; therefore no storage stability data were required.

Table 5

. Characterization and Identification of 14 C

- Residues in Rice Matrices Following a Single

Appl ication of [ 14 C] Trinexapac

- ethyl at 0.036 lb ai/A (1x Rate).

Compound/Fraction Foliage ( 0 DAT ) Foliage (7 DAT ) Foliage (21 DAT )

TRR = 0.565 ppm TRR =0.138 ppm TRR = 0.066 ppm

%TRR ppm %TRR ppm %TRR ppm

CGA

- 163935 (parent) 66.0 0.373 5.5 0.008 1.6 0.001

CGA

- 312753 ND

-- 2.5 0.003 2.6 0.002

CGA

- 275537 ND

-- 4.0 0.006 3.9 0.003

CGA

- 313458 2.2 0.012 5.1 0.007 2.6 0.002

CGA

- 179500 17.8 0.101 26.1 0.036 25.5 0.017

Total identified 86.0 0.486 43.2 0.060 36.2 0.024

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 13 of 70 Table 5

. Characterization and Identification of 14 C

- Residues in Rice Matrices Following a Single

Appl ication of [ 14 C] Trinexapac

- ethyl at 0.036 lb ai/A (1x Rate).

Compound/Fraction Foliage ( 0 DAT ) Foliage (7 DAT ) Foliage (21 DAT )

TRR = 0.565 ppm TRR =0.138 ppm TRR = 0.066 ppm

%TRR ppm %TRR ppm %TRR ppm
TLC Origin 1 ND

-- 18.3 0.025 21.8 0.014

Minor Unknowns 2 ND

-- 17.3 0.024 15.2 0.010

Unresolved 3 7.6 0.043 9.8 0.014 8.9 0.006

Total characterized 93.6 0.529 88.6 0. 122 73.2 0.048

Total extractable 98.4 0.556 92.3 0.127 87.6 0.058

Unextracted (PES2) 4 1.4 0.008 8.1 0.011 15.7 0.010

Accountability 5 99.8 100.4 103.3

Compound/Fraction S traw ( 82 DAT ) H usks ( 82 DAT ) G rain (82 DAT)

TRR = 0.161 ppm TRR = 0.168 ppm TRR = 0.085 ppm

%TRR ppm %TRR ppm %TRR ppm

CGA

- 163935 (parent) 0.9 0.001 1.8 0.003 0.1 <0.001

CGA

- 312753 ND

-- ND

-- 0.4 <0.001

CGA

- 275537 ND

-- 3.2 0.005 0.5 <0.001

CGA

- 313458 4.6 0.007 ND

-- ND

-- CGA

- 329773 ND

-- 0.7 0.001 0.4 <0.001

CGA

- 179500 4.9 0.008 8.9 0.015 11.6 0.010

Total identified 10.4 0.017 14.6 0.025 13.0 0.011

TLC Origin 1 24.9 0.040 34.5 0.058 0.7 <0.001

Minor Unknowns 2 2.4 0.004 6.7 0.011 1.7 0.001

Unresolved 3 23.2 0.037 4.8 0.008 12.0 0.010

Total characterized 60.9 0.098 60.6 0.102 27.4 0.023

Total extractable 66.9 0.108 63.3 0.106 28.7 0.024

Unextracted (PES2) 4 40.5 0.065 41.1 0.069 72.0 0.061

Accountability 5 107.4 104.4 100.7

1 Polar 14 C

- residues remaining at or adjacent to the TLC origin.

2 Unknown components each accounting for < 10 % TRR.

3 Unresolved TLC radioactivity not associated with a distinct spot or region.

4 Radioactivity remaining in residual solids following microwave extraction with PrOH/water.

5 Accountability = (Total extracted + Total unextract ed ).

Table 6. Summary of Characterization and Identification of 14 C

- Residues in Mature Rice Matrices

Following a Single Application of [ 14 C] Trinexapac

- ethyl at 0.14 lb ai/A (4x rate).

Compound/Fraction 1 Straw (60 DAT) Husks (60 DAT) Grain (60 DAT)

TRR = 1.584 ppm TRR = 2.223 ppm TRR = 1.067 ppm

%TRR ppm %TRR ppm %TRR ppm

CGA

- 163935 (parent) 1.4 0.022 6.2 0.138 6.4 0.068

CGA

- 275537 2 13.9 0.220 17.0 0.378 3.2 0.034

CGA

- 313458 2 7.2 0.114 7.4 0.165 3.2 0.034

CGA

- 329773 1.1 0.017 1.2 0.027 2.5 0.027

CGA

- 179500 2 9.1 0.144 29.9 0.665 35.6 0.380

Total identified 32.7 0.518 61.7 1.372 50.9 0.543

Polar 14 C

- residues (TLC origin) 3 30.6 0.485 9.2 0.205 14.1 0.150

Minor unknowns 10.8 0.171 6.4 0.142 12.4 0.132

Unresolved TLC radioactivity 4 12.6 0.200 6.2 0.138 3.2 0.034

Cell wall extracts 14.5 0.230 NA

-- NA

-- Pectin fraction <0.1 <0.001 NA

-- NA

-- Lignin fraction <0.1 <0.001 NA

-- NA

-- Cellulose fraction 1.3 0.021 NA

-- NA

-- Glucose NA

-- NA

-- 7.9 0.084

Total characterized 102.5 1.624 83.5 1.856 88.5 0.944

Total extractable 98.9 1.567 83.3 1.852 100 1.067

Unextracted (Final PES) 5 0.7 0.011 16.0 0.356 0 <0.001

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 14 of 70 Table 6. Summary of Characterization and Identification of 14 C

- Residues in Mature Rice Matrices

Following a Single Application of [ 14 C] Trinexapac

- ethyl at 0.14 lb ai/A (4x rate).

Compound/Fraction 1 Straw (60 DAT) Husks (60 DAT) Grain (60 DAT)

TRR = 1.584 ppm TRR = 2.223 ppm TRR = 1.067 ppm

%TRR ppm %TRR ppm %TRR ppm
Accountability 6 99.6 99.3 100

1 Total radioactivity in each fraction was calculated using data (Table C.2.2.3) from the analysis of the diethyl ether fractio n, the mild base hydrolysis of the aqueous fraction, the PrOH/water extract (straw and husk), the cell wall fractionation (straw),
and the acid/base hydrolysis of PES1 (grain).

2 Substantial amounts of these metabolites were present as conjugates . Conjugated residues of CGA

- 179500 and CGA

275537 accounted for 2 6

- 31% for their total levels in straw, 53

- 60% in husks, and 35

- 68% in grain.

3 Polar 14 C

- residues remaining at or adjacent to the TLC origin; methylation of a TLC origin fraction from straw indicated the
presence of multiple minor components.

4 Unresolved TLC radioactivity not associated with a distinct spot or region.

5 Radioactivity remaining in residual solids following chemical hydrolyses (straw/grain) or microwave extraction with

PrOH/water (husks)

. 6 Accountability = (Total extracted + Total unextrac ted).



### Wheat. In the wheat metabolism study, [1,2,6

- 14 

### C

- c yclohexyl ]trinexapac

- ethyl (97%
radiochemical purity), formulated as an EC, was applied to a field plot of spring wheat as a
single broadcast foliar application during internode elongation at 150 g ai/ha (0.13 lb ai/A, 1x

rate). Greenhouse grown wheat plants at a similar growth stage also received stem injections of

[ 14 

### C ] trinexapac

- ethyl in order to generate additional amounts of selected metabolites for detaile d
analyses. Whole wheat plants were harvested from both tests at crop maturity, 69

- 71 DAT, and

were separated into grain, husks and straw. Sample storage intervals and conditions, and the
concentrations of TRR (ppm) in mature samples were not reported. These metabolites were
identified by co

- chromatography and GC/MS analyses.

Based on the metabolite identification s and the quantitation of residues in the study report, 20.1

- 41.9% of the TRR in wheat grain, husks and straw was identified . However, subs tantial portions

of the radioactivity either remained at TLC origin s or w ere unresolved. Although the identity of
the four metabolites isolated from wheat was adequately confirmed, the percentage of the TRR
accounted for by each metabolite could not be in dependently confirmed because of the lack of

supporting raw data.

The submitted wheat metabolism study is in adequate. Although the study confirmed the

presence of trinexapac (free and conjugated), CGA

- 275537, CGA

- 329773, and CGA

- 312753 in

mature wheat commodities, the lack of supporting data precluded being able to accurately
quantify metabolite levels. The following deficiencies were also noted: (i) supporting

information from the field phase of the study was not included in the study report; (ii) fo rage or hay samples were not collected for analysis; (iii) no information was provided on sample storage
conditions and intervals; (iv) no supporting storage stability data were provided; and (v)

concentrations of radioactivity (ppm) in straw, grain and hu sks were not reported

Table 7. Characterization and Identification of 14 C

- Residues in Mature Wheat Matrices Following

a Single Foliar Application of [ 14 C] Trinexapac

- ethyl at 0.13 lb ai/A. 1

Fraction/Metabolite 2 % Total Radioactive Residues

Grain Husks Straw

CGA

- 275537 (II 2 ) 3.1 NA 2.4

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 15 of 70 Table 7. Characterization and Identification of 14 C

- Residues in Mature Wheat Matrices Following

a Single Foliar Application of [ 14 C] Trinexapac

- ethyl at 0.13 lb ai/A. 1

Fraction/Metabolite 2 % Total Radioactive Residues

Grain Husks Straw

CGA

- 329773 (II 3 ) 10.9 NA 3.1

CGA

- 312753 (I 2a ) ND 4.3 1.8

Trinexapac (I 5 ) 27.9 16.7 12.8

Total Identified 41.9 21.0 20.1

TLC Unknowns (I 1 , I 4 , II 4 ) 2.4 6.7 2.9

TLC origin (II 1 ) 3 6.8 10.0 8.0

Unresolved TLC radioactivity 31.9 47.2 59.6

Soxhlet MeOH extract 1.7 1.5 3.8

Total Characterized 84.7 86.4 94.4

Total Extracted 80.3 85.0 98.0

Unextracted (PES) 4 15.1 11.4 11.2

Accountability 5 95.4 96.4 109.2

1 Quantitative data were taken directly from Table 1 of the MRID.

2 The exact quantities of each metabolite in each matrix could not be independently confirmed by the reviewer. Amounts are
likely overestimations of the actual amounts of each metabolite present. TLC designations are listed in parentheses.

3 Polar 14 C

- residues remaining at the TLC origin.

4 Residues remaining after based hydrolysis of grain and propanol/water (220oC) extractions of husks and straw.

5 Accountability = (Total extract ed + Total unextract ed ).

Four of these fractions contained sufficient radioactivity for TLC analysis, and the following TLC components were

isolated: II 2 , II 3 , trinexapac, and II 4

. ND = not detected; NA = fraction not analyzed.



### HED Conclusions

The registrant submitted rice, grass and wheat metabolism studies on [1,2,6

- 14 

### C

c yclohexyl ]trinexapac

- ethyl. The major metabolite in rice and grass is metabolite CGA 179500.
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 c ycle. However, given the levels of exposure observed in submitted

studies, ROCKS does not expect this to be a significant toxicity pathway. Therefore the
tricarboxylic acid metabolite does not need to be included as a residue of concern.

The nature o f trinexapac

- ethyl residues in grass and cereal grain commodities is understood

based on the available grass and rice studies. 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, D390121, 7/12/11)

.

860.1300 Nature of the Residue

- Livestock

DER Reference s : 48043705.der & 45898905 (goat metabolism) and 4 8043704.der (poultry metabolism)



### Goat

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 16 of 70 In the ruminant metabolism study (MRID 45898905) , two dairy goats were dosed orally via

capsules once a day for 4 consecutive days with [1,2,6

- 14 

### C

- 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

. Samples of feces, urine and milk were collected daily, and blood

samples were collected immediately before sacrifice, ~6 hours following the final dose. Samples
of muscle (leg and tenderloin), fat (perirenal and omenta l), kidneys, liver, bile, and GI tract were
collected at necropsy. Individual samples from each animal were radioassayed, and composite

samples from both animals were used for further analysis of metabolite profiles.

The excretion and recovery of radioac tivity were similar for the two goats , with 87.3

- 90.6% of

the dose being recovered. Excretion occurred primarily via the urine (76.6

- 82.8% dose), with
only limited excretion in the feces (1.5

- 3.4% dose) and milk (0.02

- 0.07% dose). Urinary

excretion was r apid and relatively steady with 20.6

- 23.6% of the dose being excreted in the urine

on a daily basis. The levels of radioactivity in milk also indicated that excretion was rapid.
Concentrations of radioactivity in milk peaked each day in the p.m. samples (0.044

- 0.102 ppm)

collected 7 hours after each dose and were 1/3 rd 

### to 1/8 th 

### as high as they were in the subsequent

a.m. samples. 14 

### C

- Residues in milk peaked within one day of dosing at 0.078 ppm.

At sacrifice on Day 4 (6 hours post

- dose), radioactivity remaining in the GI tract accounted for

2.7

- 4.0% of the dose and blood accounted for 1.3

- 3.1% of the dose. Radioactivity remaining in
the edible tissues (muscle, fat, liver, and kidneys) accounted for 0.9

- 1.4% of the dose.
Concentrations of radioactivity in composited tissue samples were highest in kidneys (5.90 ppm),

followed by liver (0.802 ppm), muscle (0.275 ppm) and fat (0.106 ppm).

TABLE 8

. Characterization and Identification of 14 C

- Residues in Tissues and Milk from Goats Dosed

for 4 Days with [ 14 C] Trinexapac

- ethyl at 150 mg ai/day (110 ppm)

. Compound Liver Kidney Muscle Fat Milk

- Day 2 (pm)

TRR= 0.802 ppm TRR= 5.903 ppm TRR= 0.275 ppm TRR= 0.106 ppm TRR = 0.076 ppm

% TRR ppm % TRR ppm % TRR ppm % TRR ppm %TRR ppm

CGA

- 163935 (parent) ND

-- ND

-- ND

-- ND

-- ND

-- CGA

- 179500 66.0 0.529 85.3 5.036 96.8 0.266 83.9 0.089 85.3 0.065

CGA

- 113745 16.3 0.131 6.0 0.354 0 0 11.4 0.012 0 0

Total identified 82.3 0.660 91.3 5.390 96.8 0.266 95.3 0.101 85.3 0.065

Minor unknowns

Unknown G3 5.1 0.041 ND

-- 3.5 0.010 ND

-- ND

-- Unknown G4 1.5 0.012 ND

-- ND

-- 1.5 0.002 ND

-- Unresolved polar

residues 1 5.5 0.44 3.6 0.212 ND

-- ND

-- 2.0 0.002

Total characterized 90.3 0.724 95.8 5.656 100.8 0.277 95.3 0.101 94.3 0.072

Total extractable 94.5 0.758 95.0 5.608 103.6 0.285 97.8 0.104 90.3 0.069

Unextracted 1 8.0 0.064 4.5 0.266 4.0 0.011 ND

-- 9.0 0.007

Accountability 2 102.5 99.5 107.6 98.1 100.0

1 Unidentified polar residues associated with the column void volume.

2 Residues remaining in solids a fter solvent extractions.

3 Accountability = (Total extractable + Total unextract ed )/(TRR from combustion analysis; see TABLE C.2.1)*100.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 17 of 70 Syngenta Crop Protection, Inc. submitted a second goat metabolism study (MRID 48043705). In

this ruminant metabolism study, one dairy goat was dosed orally via capsules once a day for 4

consecutive days with [1,2,6

- 14 

### C

- cyclohexanedione]trinexapac

- ethyl (97.7% radiochemical
purity) at a dose of 150 mg ai/day

. Th e actual mean dosing rate from d ay 1

- 4 was 103.7 ppm.

Samples of feces, urine and milk were collected twice daily and blood samples were collected
immediately before sacrifice, ~6 hours following the final dose. Samples of liver, kidneys, fat
(omental and perirenal), muscle (loin and hindq uarter), bile, and GI tract were collected at

necropsy. Individual samples were radioassayed.

Total radioactive residues (TRR) were determined by direct analysis (LSC or combustion/LSC)

for each of the goat matrices. Excretion occurred primarily via the urine (84.31% dose), with
only limited fecal excretion (3.4% dose). Excretion via the milk was also limited with milk
accounting for 0.05% of the dose over four days. Excretion via the urine was rapid and peaked

each day in the afternoon collection with 15.01

- 23.41% of the dose being excreted in the urine
on a daily basis. The lower levels in urine on Day 4 most likely reflected the short (6

- hour)
interval between dosing and sacrifice on the final day. The rapid rate of excretion was also

evidenced by t he concentrations of radioactivity in milk over time. The concentration of
radioactivity in milk peaked each day in the afternoon samples (0.046

- 0.073 ppm) and was 6x

- 8x
lower in the subsequent morning samples collected prior to dosing. Maximum residues in milk

peaked on Day 4.

At sacrifice on Day 4 (6 hours post

- dose), radioactivity in the GI tract accounted for 2.25% of

the dose and bile accounted for 0.01% of the dose. Radioactivity remaining in the edible tissues
(muscle, fat, liver and kidneys) acc ounted for 0.56% of the dose. Concentrations of radioactivity
were highest in kidneys (5.201 ppm), reflecting the high level of urinary excretion, and lowest in

fat (0.251 ppm). TRR were 0.318 ppm in muscle and 1.544 ppm in liver. Overall, the total

amo unt of administered dose recovered was 91.46%.

The radioactivity recovered in the second goat metabolism study ( MRID 48043705) followed
similar patterns as the previous study (MRID 45898905)

. The TRR was not characterized in the

second study.

Poultry

Syngenta Crop Protection, Inc. has submitted a study investigating the metabolism of 14 

### C

trinexapac

- ethyl (cyclohexadione ring label) in l aying hen s; the specific activity was 40.9

μCi/mg . The test substance was administered orally via gelatin capsule to f ive hens at a nominal
rate of 10 ppm in the diet for 10 consecutive days. The actual mean dosing rates from Day 1

- 10

were 8.14 to 10.1 ppm. Eggs were collected daily and the whites and yolks were separated. On

average the hens produced one egg per day. Exc reta were collected once daily and cage was h

was collected after sacrifice . The hens were euthanized approximately 22 hours after
administration of the final dose. After sacrifice, the peritoneal fat, s ubcutaneous fat with skin

attached , liver, kidney, mus cle (breast and thigh), and the GI tract with contents were collected.
Individual samples of eggs, tissues and excreta were stored frozen for a maximum of 26 days

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 18 of 70 prior to analysis. The composite egg white sample was extracted, fractionated and
chromatogr aphically profiled within 6 months of necropsy; therefore, no storage stability data

are required to support the study.

Total radioactive residues (TRR) were determined by direct analysis (LSC or combustion/LSC)

for each of the hen matrices. The TRR we re below 0.01 ppm for the edible tissues and egg yolks,

therefore

, they were not further investigated. The TRR expressed as ppm trinexapac

- ethyl
equivalents in egg whites from all five hens ranged from 0.005 to 0.031 ppm , while the TRR in

egg yolks ranged from <0.003 to 0.009 ppm. Egg white samples were composited from eggs
collected on dose Days 6 through 10 from hens and the TRR was determined by both by direct
LSC (0.017 ppm) and from the summation of the activity in initial extracts and solids (0.016

ppm). The TRR from the summation of the extractable and nonextractable radioactivity
following the initial extraction was in agreement with the radioactivity determined by direct
combustion/LSC analysis ( 95.7 %). The majority of the administered dose (88

- 9 1%) was found to

have been excreted. Cage wash samples accounted for 0.31

- 2.32% of the dose administered

dose.

Significant quantities of radioactive residues resided in the organic phase (61.3% TRR ; 0.010
ppm) and an insignificant amount remained in the aqueous phase (8.2% TRR ; 0.001 ppm). The
organosoluble residue was further analyzed by thin layer chromatography ( TLC ) to identify the

residues. No further analytical work was carried out on the post

- extraction solid (PES) (10.6%

TRR; 0.002 ppm). Based on the analysis of the composite egg whites, the major residues were
identified as the parent compound trinexapac

- ethyl (31.0% TRR; 0.005 ppm) and its metabolite,

CGA

- 179500 (20.2% TRR; 0.003 ppm). At least two unknowns were present in the extract, none

of w hich represented greater than 3.2% TRR (<0.001 ppm).

HED Conclusions

The metabolism of trinexapac

- ethyl was investigated in both laying hens and lactating goats

. F or poultry, the major residues were identified as the parent compound trinexapac

- ethyl (31% TRR)
and its metabolite CGA 179500 (20% TRR). In a ruminant metabolism study, trinexapac

- ethyl

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

### C

- residue in milk a nd all tissues
was the acid metabolite, CGA 179500, accounting for 66% of the TRR in liver and 84

- 97% of
the TRR in milk and the remaining tissues. The metabolite CGA 113745 was also identified in

the liver (16% TRR), kidney (6% TRR) and fat (11%), but wa s 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 it also of less toxicological concern.

The nature of the residue in livestock is adequat ely unders tood 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, D390121, 7/12/11)

.

860.1340 Residue Analytical Methods

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 19 of 70 Plant method

DER Reference s: 4 8043702.der (Includes MRID 48043703 )



### In conjunction with the previous grass petition (PP#3F6571; DP#s 328 850, 328853, 32 8898 ) , the
petitioner provided an HPLC/MS method (Syngenta Method No. 110

- 10) for collecting data and

enforcing tolerances for trinexapac

- ethyl residues in grass commodities. This method

determined free residues of trinexapac in plant commodities. Based on the results of the

metabolism studies, HED conclude d that residues of both free and conjugated trinexapac need to be regulated . As a result, the analytical method is not adequate for tolerance enforcement or risk
assessment purposes. It needed to be revised to include an enzymatic and/or mild acid
hydrolysis step to release c onjugated residues of trinexapac

.

Syngenta Crop Protection, Inc. has submitted an analytical method description and validation

data for a data collection method, GRM020.01A, for the determination of residues of trinexapac
acid (CGA179500) in crop matrices using high performance liquid chromatography with triple

quadr u p o le mass spectrometric (LC

- MS/MS) analysis (MRID 48043702) . Analytical Method

GRM020.01A is a modified version of Syngenta Analytical Method 110

- 01 for the
determination of residues of CGA179500 using HPLC

- MS/MS instrumentation. Method

GRM020.01A was used for data collection in /on plant samples collected from crop field trial and

processing s tudies associated with the current petitions

. The new method includes a strong acid
hydrolysis/extraction procedure to release both “free” and “conjugated” residues of CGA179500
from field grown grass commodities to fulfill the data deficiencies noted in a previous petition

review (DP#s 328858, 328853, and 323398 ). For grass grown f or seed and crops, the LOQ is

0.01 ppm.

Syngenta submitted radiovalidation data to evaluate the efficiency of the extraction methodology
presented in Method GRM020.01A for e xtracting CGA179500 from field grown grass
commodities (forage, straw, and seed screenings). The extraction efficiencies were determined

by comparing the radioactivity in the sample extracts with the total radioactive residues (TRR) in
forage, straw, and seed screening samples from a previously conducted metabolism study. The

extraction efficiencies were determined to be 112%, 101%, and 89% in the 14 

### C

- labeled forage,

straw, and seed screening samples, respectively.

Analytical Method GRM020.01A was successfully validated using samples of field grown grass

commodities (forage, straw, seed screenings, and seeds) at 0.01 and 0.1 ppm or higher.
Acceptable mean recoveries ranging from 89% to 99% with relative standard dev iations less than

20% for each matrix tested.

An independent laboratory validation (ILV) study was also conducted using samples of wheat
grain, wheat forage, and wheat straw fortified with CGA179500 at 0.010 and 0.10 ppm.

Acceptable mean recoveries ran ging from 90% to 102% with relative standard deviations less

than 20% were found for each matrix tested.

HED Conclusions

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 20 of 70 Th e submitted LC/MS/MS method, Method GRM020.01A

, is adequate for data collection and

tolerance enforcement. T he method showed that the parent (trinexapac

- ethyl) ra p idly undergoes
hydrolysis of the ethyl ester to form trinexapac acid (CGA179500)

. The radiovalidation study
proved efficiency of the extraction methodology used in the residue method. The method has

been adequately va lidated in an independent laboratory.

Livestock Method

DER Reference s : 4 8043706.der

, 48043707 .der, 48043708 .der



### Syngenta Crop Protection, Inc. has submitted an analytical method description and validation

data for a data collection method, REM 137.14, for the determination of residues of trinexapac

acid in livestock matrices using high performance liquid chromatography with triple quadrupole

mass spectrometry (LC

- MS/MS) analysis. The samples are quantitatively determined by LC

MS/MS with multiple reaction monitoring (MRM). The LOQ was established as 0.01 ppm for
egg, kidney, liver, muscle, and fat and 0.005 ppm for milk. The limit of detection (LOD) was

determined to be 0.0007 ppm.

Syngenta submitted radiovalidation data to evaluate the efficiency of the extraction methodology
presented in Method REM 137.14 for extracting [ 14 

### C]trinexapac acid from goat liver and

chicken egg white samples. The extraction efficiencies were dete rmined by comparing the
radioactivity in the sample extracts with the total radioactive residues (TRR) in goat liver and
chicken egg white samples from previously completed dosing and metabolism studies. The

extraction efficiencies were determined to be 1 02% and 105% in the 14 

### C

- labeled goat liver and
chicken egg white samples, respectively.

Method REM 137.14, subsamples of 14 

### C

- labeled goat liver and chicken egg whites were
extracted according to Method REM 137.14. Aliquots of the sample extracts were then
quantified by LC

- MS/MS analysis. Residues of CGA179500 averaged 1.117 ppm for the 14 

### C

labeled goat liver samples and were <0.01 ppm for the 14 

### C

- labeled chicken egg white samples.
The method was determined by comparing the results from the HPLC

- MS/MS analysis with the
sample profiling data. The residues of CGA179500 were below the LOQ (0.01 ppm) in chicken

egg whites.

Metho d REM 137.14 was successfully validated for trinexapac acid in milk, hen eggs, bovine

kidney, bovine liver, bovine muscle and bovine fat. Acceptable mean recoveries ranging from
81% to 107% with relative standard deviations less than or equal to 20% were found for each

matrix tested.

A successful independent laboratory validation (ILV) trial was conducted using samples of
bovine muscle and bovine milk in sets consisting of one blank, two unfortified control samples,

five samples fortified at the LOQ (0. 01 ppm for muscle and 0.005 ppm for milk) and five
samples fortified at tenfold the LOQ (0.10 ppm for muscle and 0.05 ppm for milk). Acceptable
mean recoveries ranging from 90% to 101% with relative standard deviations less than 20% were

found for each ma trix tested.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 21 of 70 HED Conclusions

Adequate method validation data have been submitted for Method REM137.14 for the
determination of residues of trinexapac acid in/on livestock commodities. The petitioner

submitted 14 

### C

- labeled goat liver and chicken egg whit e samples to radiovalidate the method

REM 137.14 for the purpose of animal tolerance enforcement. The method has been adequately
validated in an independent laboratory.

860.1360 Multiresidue Methods

DER Reference : 45898908.der



### 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

- methylcarbamate 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 D G1 and DG13
with electron 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 ade quate GLC response was obtained for
methylated trinexapac using Module DG1 (RRT = 0.52). However, neither trinexapac

- ethyl nor

methylated trinexapac were recovered from the Florisil cleanup procedures. Therefore, testing
through Protocols E and F was not conducted.

HED Conclusions

These data indicate FDA multi

- residue methods are not suitable for determining residues of

trinexapac

- ethyl and trinexapac in plant commodities. The data will be forwarded to the U.S.

FDA for further evaluation.

860.1380 Storage Stability

DER Reference s: 45898903.der (wheat and rapeseed)

, 47101601.der (grass)

\



### Plant commodities

Syngenta submitted data supporting the frozen storage stability of trinexapac (CGA179500) in
rapeseed and wheat grain and straw (MRID 45898903). Samples of homogenized wheat grain,

wheat straw, and rapeseed were fortified with trinexapac at 0.5 ppm and stored in plastic bottles

at

- 20oC for up to 2 years. R esidues of trinexapac were determined using a HPLC/UV two

column method, Ciba

- Geigy Method REM 137.02. Wheat and barley CGA 179500 were

extracted by shaking a homogenize subsamples with a 3+7 mixture of methanol and aqueous
phosphate buffer (pH 7). An ext ract aliquot is transferred to a solid phase extraction cartridge.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 22 of 70 After washing with methanol and water, CGA 179500 is eluted with sulfuric acid (0.1 N) and
partitioned into dichloromethane using HPLC with UV

- detection. The method was adequately

validat ed (fortified at 0.5 ppm and ranged from 80

- 106%) by the analysis of the freshly fortified
samples of wheat grain, wheat straw and rapeseed

.

A storage stability study (MRID 47101601) with CGA

- 163935 (trinexapac

- ethyl) and CGA

179500 (trinexapac) in gras s (clippings and thatch + sod) was also submitted . Untreated s amples
of each of these commodities were homogenized and fortified with either CGA

- 163935 or CGA

179500 at a level of 2 ppm. S amples were placed in frozen storage at approximately

- 20 oC and

a nalyzed at storage intervals of 12 days (CGA

- 163935 bluegrass thatch + sod only), 27/30/31
days , 58/60/62, 118/124 days (bluegrass only), 167/171/181/183 days (Bermuda grass and

bluegrass thatch + sod only), 213/241 days (bluegrass thatch + sod only), and 273/274/282 days
(Bermuda grass only)

. The study did not report the results for the 0 day and extraction and
analysis dates were not reported.

Three methods were used to produce analytical data in this study. The first method CIBA

GEIGY M ethod AG

- 577 titled “Analytical Method for the Determination of CGA

- 163935 in

Turf Grass and Thatch by High Performance Liquid Chromatography With Column

- Switching in

Soil” was used to determine residues of CGA

- 163935 in grass clippings and thatch + sod. The

second me thod CIBA

- GEIGY M ethod AG

- 582 titled “Analytical Method for the Determination

of CGA

- 179500 in Turf Grass and Thatch by High Performance Liquid Chromatography With

Column

- Switching” was used to determine residues of CGA

- 179500 in grass clippings and

thatch + sod. The third method ABC Laboratories M ethod 052190 titled “Analytical Method for

the Determination of CGA

- 163935 and CGA

- 1795 00 in S oil” was used to determine residues of

CGA

- 163935 and CGA

- 179500 i n NY thatch + sod samples due to unacceptable perfor mances

of methods AG

- 577 and AG

- 582. A brief description of each method was included in the study

submission. The petitioner indicated that Methods AG

- 577 and AG

- 582 have been validated in
grass and thatch and that Method 052190 has been validated in soi l. The LOQ was not reported
for any method.

R esidues of CGA

- 163935 and CGA

- 179500 appear to be stable in/on Bermuda grass and
bluegrass clippings for up to 6 months. R esidues of CGA

- 163935 and CGA

- 179500 appear to be

relatively steady in/on Bermuda gr ass thatch + sod for up to 9 months but were variable in/on
bluegrass thatch + sod due to the change in method. Since 0

- day recoveries were not reported,

the relative decline could not be assessed.

Livestock commodities

To support the sample storage durations i n the dairy cattle feeding study, a concurrent storage stability study was conducted using control samples of each matrix fortified with trinexapac,

CGA 179500 at 0.05

- 0.20 ppm. S amples were stored frozen (≤

- 18 o 

### C) and then analyzed with

freshl y fortified samples ; actual dates of analysis were not provided . The petitioner s tated that
the storage stability intervals were chosen to cover the time period between arrival of the
samples at the analytical laboratory and analysis. The mean corrected recoveries from the

storage stability study (corrected for concurrent recoveries) were 82%, 89%, 85%, 85%, 96%,
and 102% for muscle, milk, liver, kidney, fat, and blood, respectively.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 23 of 70 To support the sample storage durations in the poultry feeding study

, a concurrent storage stability study was conducted using control samples of chicken egg and tissue fortified with
CGA179500 at a target level of 0.1 ppm . These samples were stored frozen (

- 20 °C) and then
analyzed at 0 and 31

- 82 days with freshly fortified samples. Corrected recoveries of

CGA179500 from poultry samples were 95

- 97% for eggs, 94% for skin and fat, 98

- 103% for

liver, 104

- 117% for kidney, and 98

- 100% for muscle

.

Sample storage conditions and intervals

The storage durations and conditions o f samples from the crop field trials

, processing , and

livestock feeding studies submitted to support th ese petition s are presented in Table 9

.

Table 9 . Summary of Storage Conditions and Durations o f Samples from Crop Field Trial

, Processing , and
Livestock Feeding Studies.

Matrix Analyte Storage

Temperature

(°C) Actual Storage

Duration Interval of Demonstrated Storage Stability

PP#0F7719

Grass seed
screenings CGA179500 - 10 9.8

- 17.1 months 6

- 9 months for grass commodities

12

- 24 months for wheat (grain and straw)

Grass straw CGA179500

- 10 7.3

- 10.9 months

Grass forage CGA179500

- 10 8.4

- 10.1 months

Grass hay CGA179500

- 10 6.8

- 9.9 months

Milk CGA179500 ≤

- 18 181 days 1 Based on the results of a concurrent storage
stability study, 121 days for milk, 95 days for
tissues, 101 days for fat, and 83 days for blood. Cattle tissues CGA179500 152 days 1

Fat CGA179500 152 days 1

Blood CGA179500 152 days 1

Chicken eggs CGA179500

- 20 22

- 82 days Based on the results of a concurrent storage
stability study, 82 days for eggs, 56 days for

skin + fat

, 57 days for liver

, 54 days for kidney,

and 31 days for muscle. Chicken skin + fat CGA179500 29

- 55 days

Chicken liver CGA179500 28

- 55 days

Chicken kidney CGA179500 35

- 54 days

Chicken muscle CGA179500 28 days

PP#0F7720

Barley hay CGA179500

- 20 2.6

- 15.1 months No data available for barley commodities

12

- 24 months for wheat (grain and straw) Barley straw CGA179500

- 20 2.1

- 13.4 months

Barley grain CGA179500

- 20 2.2

- 16.1 months

Barley grain (RAC) CGA179500 ≤10 ° F at

processor

- 20 ± 5 °C at laboratory 353

- 379 days No data available for barley commodities

12

- 24 months for wheat (grain and straw)

Pearled barley CGA179500 335

- 350 days No data available for barley processed

commodities Barley flour CGA179500 331

- 346 days

Barley bran CGA179500 334

- 349 days

Wheat forage CGA179500

- 10 11.6

- 16.0 months 6

- 9 months for grass commodities

12

- 24 months for wheat (grain and straw) Wheat hay CGA179500

- 10 11.5

- 15.1 months

Wheat straw CGA179500

- 10 8.9

- 13.8 months

Wheat grain CGA179500

- 10 9.8

- 17.1 months

Wheat grain (RAC) CGA179500 ≤10 ° F at

processor 341

- 416 days

AGF CGA179500 334

- 384 days

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 24 of 70 Table 9 . Summary of Storage Conditions and Durations o f Samples from Crop Field Trial

, Processing , and
Livestock Feeding Studies.

Matrix Analyte Storage

Temperature

(°C) Actual Storage

Duration Interval of Demonstrated Storage Stability

Bran CGA179500

- 20 ± 5 °C at laboratory 280

- 474 days No data available for wheat processed

commodities Flour CGA179500 335

- 385 days

Middlings CGA179500 235

- 471 days

Shorts CGA179500 236

- 470 days

Germ CGA179500 237

- 469 days

Sugarcane CGA179500

- 10 14.6

- 22.2 months No data available for sugarcane

6

- 9 months for grass commodities

12

- 24 months for wheat (grain and straw) Sugarcane (RAC) CGA179500 - 10 457

- 658 days

Molasses CGA179500

- 10 439

- 535 days No data available for sugarcane processed

commodities Refined Sugar CGA179500 - 10 438

- 534 days

1 The actual duration for samples in frozen storage from the cattle feeding study was not provided. The reviewer calculated th e maximum estimated time between collection and analysis based on study dates provided on page 7 of the report (first day of
sample collection and last day of sample analysis).



### HED Conclusions

The available storage stability data for wheat (grain and straw) are adequate to support the
storage durations and conditions of grass, barley, wheat, and sugarcane RAC samples

. Although

some decline was noted in wheat straw after 2 years of storage, trinexapac residues were stable

for 24 months for wheat grain

, 12 months for wheat straw, and up to 9 months in grass

. For
samples of straw (dry forage) and o ilseeds stored for up to 24 months, correction factors of 1.33x

and 1.18x should be applied when calculating residues.

Since actual storage durations of the study samples from the dairy cattle feeding study were not

provided, it is uncertain if the submit ted concurrent storage stability data support the storage
durations for study samples. Information on storage durations for the study samples is needed. If
study samples were stored longer than the demonstrated storage stability interval, additional

stora ge stability data demonstrating the stability of CGA 179500 will be required to cover the
storage durations for the study samples. The concurrent storage stability d ata support the storage

conditions and durations of CGA179500 for the poultry livestock fe eding study samples.

860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 25 of 70 860.1480 Meat, Milk, Poultry, and Eggs

The livestock feedstuffs included in the current petitions are grass (forage, hay and silage),
barley (hay, straw and grain), wheat (forage, hay, straw, grain and milled byproducts) and
sugarcane molasses. The potential dietary exposure of livestock to trinexapac

- ethyl residues was

calculated below in Table 1 0 using recent Agency guidance on calculating dietary exposure from
“reasonably balanced” livestock diets (ChemSAC draft memo, 6/2008). Also, ChemSAC has

considered revising the cur rent guidance regarding the use of tolerance

– level residues when

estimating livestock dietary burdens. The u se of the highest residue rather than the tolerance
would bring EPA into harmonization with our NAFTA partners, with other countries, and with

OEC D guidance.

The calculated dietary burdens of trinexapac

- ethyl are 1. 7 ppm for beef cattle, 1. 8 ppm for dairy
cattle, 3.0 ppm for poultry, and 1. 4 ppm for swine. The bases for these calculations are shown in

the table below.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 26 of 70 Table 1 0

. Maximum Re a sonabl e Dietary Burdens (MRDB) of Trinexapac

- Ethyl R esidues Fed to Livestock.

Feedstuff Type 1 % Dry

Matter 2 % Diet 2 Highest

Residue (ppm) 3 Dietary Contribution
(ppm) 4

Beef Cattle : 15% R, 80% CC, 5% PC

Wheat, hay R 88 15 1.3 0. 2 2

Barley, grain CC 88 50 1.3 0.74

Wheat, milled byproducts 5 CC 88 20 2.3 0.52

Sugarcane , molasses/pulp CC 75 10 1.6 0. 21

Untreated PC NA 5 NA 0.0

TOTAL BURDEN

-- -- 100

-- 1. 7

Dairy Cattle : 45% R, 45% CC, 10% PC

Barley, hay R 88 20 0. 54 0.1 2

Wheat, hay R 88 20 1. 3 0.3 0

Untreated R 88 5 NA 0.0

Wheat, grain CC 89 15 4.0 0.67

Wheat, milled byproducts CC 88 20 2.3 0.52

Sugarcane , molasses/pulp CC 75 10 1.6 0. 21

Untreated PC NA 10 NA 0.0

TOTAL BURDEN

-- -- 100

-- 1. 8

Poultry : 75% CC, 25% PC

Wheat, grain CC 89 75 4.0 3.0

Untreated PC NA 25 NA 0.0

TOTAL BURDEN

-- -- 100

-- 3.0

Swine : 85% CC, 15% PC

Barley, grain CC 88 20 1.3 0. 26

Wheat, milled byproducts CC 88 50 2.3 1.15

Untreated CC NA 15 NA 0.0

Untreated PC NA 15 NA 0.0

TOTAL BURDEN

-- -- 100

-- 1. 4

1 R: roughage; CC: carbohydrate concentrate; PC: protein concentrate.

2 OPPTS 860.1000 Table 1 Feedstuffs (June 2008).

3 Highest residue= trinexapac

- ethyl as trinexapac, CGA 179500

4 Contribution = ([tolerance /% DM] x % diet) for beef and dairy cat tle; c ontribution = (tolerance x % diet) for poultry and swine.

5 For wheat milled byproducts: use the highest value of middlings, bran, and shorts. Based on the wheat processing
study (refer to section 860.1520) the maximum expected residues are 2.3 ppm (average concentration factor of
3.2 x HAFT of 0.73 ppm) for wheat middlings.



### The Agency notes that f

orage regrowth has not been considered a feedstuff in the proposed cattle

diets. We do not consider forage regrowth a significant feedstuff because:

1) Mos t of the areas growing grass for seed are not near fe edlots or dairy (milkshed)

.

2) Fields reserved for grass grown for seed are not grazed. Forage regrowth could be
harvested as green chop or made into grass silage, but this would be used in cow

- calf

opera tions, or fed to local growing cattle and not to Table 1 production reference

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 27 of 70 animals."

Livestock feeding studies

DER Reference s: 4 7101603 .der.doc (d airy cattle feeding study)

, 4 8043604 .der.doc ( p oultry feeding study)



### Dairy cattle feeding study

Syngenta Crop Protection, Inc. submitted a cattle feeding study in which three groups of dairy
cows (3 cows/group) were dosed orally with capsules containing trinexapac as CGA 179500 at
target doses equivalent to 2.01 ppm (1 x)

, 5.59 (2.8x) ppm and 19.9 (10 x) ppm in their diet (dry

weight basis) for 29 to 30 consecutive days. The actual dose rates were 2.03, 5.65 and 20.1 ppm.
Cows were milked twice daily, and milk samples were composited daily for each cow. Samples
of milk from Study Days 0, 1, 2, 3, 5, 8, 12, 15, 19, 22, and 28 from all dose groups were

analy zed

. Livestock commoditie s were sacrificed ~20

- 23 hours after the final dose on Study

Day s 2 9 and 30. Samples of liver, kidney, fat (perirenal and omental), muscle (round, loin and
diaphragm) and b lood were collected from each cow at sacrifice.

Milk and tissue samples were analyzed for residues of CGA 179500 using modified Analytical
Method REM 137.12. The limits of quantitation (LOQs) for tissue, milk, and blood samples

were 0.02, 0.005 and 0.0 1 ppm for CGA 179500, respectively. This method is adequate for data
collection based on acceptable concurrent method validation data. According to the guidelines,
if detectable residues occur in whole milk at any dosing level, analysis of a few samples of milk

fat is advisable to show how residues partition into that commodity. CGA 179500 residues were
detected at a maximum level of 0.010 ppm in the 10x dosing group. Milk fat samples were not
analyzed.

Actual storage intervals were not reported. The maximum possible frozen storage intervals from
collection to analysis were 181 days for milk samples, and 152 days for tissue and blood samples

(based on the days of first collection and last sample analysis). A concurrent storage stability
study was cond ucted using control samples of each matrix fortified with CGA 179500 at 0.05

- 0.20 ppm. According to the study report, t hese samples were stored frozen (≤

- 18 o 

### C) and then

analyzed with freshly fortified samples ; actual dates of analysis were not provided

. The average
recoveries from the storage stability study (corrected for concurrent recoveries) were 82%, 89%,
85%, 85%, 96%, and 102% for muscle, milk, liver, kidney, fat, and blood, respectively.

In muscle samples (tenderloin, round and diaphragm) and fat samples (perirenal and omental),
there were no CGA 179500 residues detected above the LOQ (0.02 ppm) for any dose group,
with the exception of one diaphragm sample and one perirenal fat sample from the 10x group

with residues of 0.02 ppm. There were only two liver samples with residues above the LOQ.
Both samples were from the 10x dose group and both had residues at 0.03 ppm. Average

r esidues of 0.03, 0.04, and 0.17 ppm were found in kidney samples from dose groups 1x, 3x, and

10x, respectively. The average residues found in the blood samples were 0.02, 0.03, and 0.13
ppm from dose groups 1x, 3x, and 10x, respectively. CGA 179500 was not detected above the
LOQ (0.005 ppm) in milk samples collected from the cows in the 1x or 3x dose groups. In milk

of dose group 10x, residues were found in the range of <0.005 to 0.011 ppm.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 28 of 70 A summary of residue data from the ruminant feeding study with trinexapac

- ethyl is presented in

Table 11

.

T able 11 . Summary of Residue Data from Dairy Cattle Feeding Study with C GA 179500

Matrix Feeding

Level
(ppm) Residue Levels (ppm)

n Min. Max. Median Mean Std. Dev.

Muscle (loin) 2.03 3 <0.02 <0.02 <0.02 <0.02

-

5.65 3 <0.02 <0.02 <0.02 <0.02

-

20.1 3 <0.02 <0.02 <0.02 <0.02

-

Muscle

(round) 2.03 3 <0.02 <0.02 <0.02 <0.02

-

5.65 3 <0.02 <0.02 <0.02 <0.02

-

20.1 3 <0.02 <0.02 <0.02 <0.02

-

Diaphragm 2.03 3 <0.02 <0.02 <0.02 <0.02

-

5.65 3 <0.02 <0.02 <0.02 <0.02

-

20.1 3 <0.02 0.02 0.02 0.02 0.000

Liver 2.03 3 <0.02 <0.02 <0.02 <0.02

-

5.65 3 <0.02 <0.02 < 0.02 <0.02

-

20.1 3 <0.02 0.03 0.03 0.027 0.006

Kidney 2.03 3 0.03 0.03 0.03 0.03 0.000

5.65 3 0.03 0.05 0.04 0.040 0.010

20.1 3 0.08 0.29 0.13 0.167 0.110

Fat (Perirenal) 2.03 3 <0.02 <0.02 <0.02 <0.02

-

5.65 3 <0.02 <0.02 <0.02 <0.02

-

20.1 3 <0.02 0.02 0.02 0.020 0.000

Fat (Omental) 2.03 3 <0.02 <0.02 <0.02 <0.02

-

5.65 3 <0.02 <0.02 <0.02 <0.02

-

20.1 3 <0.02 <0.02 <0.02 <0.02

-

Blood 2.03 3 0.014 0.023 0.016 0.018 0.005

5.65 3 0.027 0.036 0.031 0.031 0.005

20.1 3 0.059 0.167 0.15 0.125 0.058

Milk 2.03 3 <0.005 <0.005 <0.005 <0.005

-

5.65 3 <0.005 <0.005 <0.005 <0.005

-

20.1 3 <0.005 0.011 0.005 0.005 0.001

1 Milk Fat samples were not analyzed

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 29 of 70 Expected secondary residues in meat and milk

To determine the need for tolerances for residues trinexapac

- ethyl as CGA179500 in milk and
tissues, the anticipated secondary residues in cattle matrices were estimated using transfer

coefficient factors calculated from the maximum residues of CGA179500 o bserved at the dose

level closest to the RBDB in the dairy cattle feeding study. The transfer coefficients (calculated
as residue level to feed level ratios) are presented in Table 12 . The transfer coefficient for each

matrix was then used to calculate t he expected secondary residues by multiplying the transfer

coefficient by the calculated dietary burden. The expected residues of CGA179500 and the
recommended tolerances based on expected residues are presented in Table 13

.

Table 12

. Residue

- Level

- to

- Feed Ratios (Transfer Coefficients) in Dairy Cattle Milk and Tissues.

Matrix Maximum Residue of

CGA179500 (ppm) Feeding Level
(ppm) Transfer

Coefficient 1

Milk < 0.0 05 2.03 0.00 2

Liver <0.02 2.03 0.0 1

Kidney 0.05 2.03 0.0 2

Muscle (loin) <0.02 2.03 0.0 1

Muscle (round) <0.02 2.03 0.0 1

Fat (perirenal) <0.02 2.03 0.0 1

Fat (omental) <0.02 2.03 0.0 1

1 Calculated from the maximum residues observed at the dose level closest to the reasonable dietary burdens (R DB )
divided by the dose level.

Table 13 . Expected Secondary Residues of CGA179500 in Meat and Milk.

Matrix Dietary Burden
(ppm) Secondary Residues 1

(ppm) Recommended Tolerance
(ppm)

Dairy Cattle

Milk 1. 8 0.00 4 Not required

Liver 1. 8 0.0 2 0.02

Kidney 1. 8 0.0 4 0.0 4

Muscle 1. 8 0.0 1 8 0.02

Fat 1. 8 0.0 1 8 0.02

Swine

Liver 1. 4 0.0 14 0.02

Kidney 1. 4 0.0 28 0.0 3

Muscle 1. 4 0.0 14 0.02

Fat 1. 4 0.0 1 4 0.02

1 Calculated from dietary burden x t ransfer coefficient from Table 12

.



### HED Conclusions

Pending submission o f information of sample storage conditions and durations, t he residue data
from the cattle feeding study are adequate to satisfy data requirements. Based on the maximum
anticipated residues, HED concludes that the following tolerances are appr opriate for the free

and conjugated residues of both parent and its acid metabolite, trinexapac in livestock

com modities: 0.02 ppm for the fat and meat of c attle, goat, horse, and sheep; 0. 0 4 ppm for the
meat byproduct of cattle, goat, horse, and sheep; a nd 0.02 ppm for the fat and meat of hog; 0.03

ppm for the meat byproduct of hog.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 30 of 70 Poultry feeding study

Syngenta Crop Protection, Inc. submitted a poultry feeding study in which three groups of laying
hen (10 hens/group; 3 replicates per group) were dosed orally with feed containing trinexapac as

CGA179500 at target doses equivalent to 3.3 ppm (1 .2 x), 9.9 pp m (3 .3x), and 33 ppm (12.3 x) in
their diet (dry

- weight basis) for 28 consecutive days. The actual dose rates were 3.7, 10 and 37
ppm. Samples of egg from Study Days 0, 1, 3, 7, 10, 14, 17, 21, 24, and 28 from all dose groups

were collected. Livestock co mmoditie s were sacrificed ~6 hours after the final dose on Study
Day 28. Samples of skin plus attached fat, peritoneal fat, liver, kidneys, and muscle (breast and
thigh) were collected from each hen and composited by replicate within each group.

Egg and tissue samples were analyzed for residues of CGA179500 using Analytical Method

REM 137.14. In each matrix, the LOQ, defined as the lowest analyte concentration at which the

methodology has been validated, is 0.01 ppm for CGA179500.

Samples were sto red at

- 20°C prior to extraction for analysis for 22

- 82 days (0.7

- 2.7 months) for

egg, 29

- 55 days (1.0

- 1.8 months) for skin and fat, 28

- 55 days (0.9

- 1.8 months) for liver, and 35

- 54 days (1.2

- 1.8 months) for muscle. All samples were analyzed within 0 to 5 days of

extraction. To support the sample storage intervals, a concurrent storage stability study was

conducted using control samples of chicken egg and tissue fortified with CGA179500 at a target
level of 0.1 ppm. These samples were stored frozen (

- 20° C) and then analyzed at 0 and 31

- 82
days with freshly fortified samples. The results show that residues of CGA179500 are stable in

frozen egg and tissue samples for up to 31

- 82 days. These data support the storage conditions

and durations for the CGA1795 00 poultry livestock feeding study samples.

Residues of CGA179500 were not detected above the LOQ (<0.01 ppm) in any egg samples
from the 3x dose group. The maximum mean residue in egg samples from the 10x dose group
was 0.01 ppm on Day 28. Egg sample s from the 1x dose group were not analyzed.

In tissues, residues of CGA179500 were below the LOQ (<0.01 ppm ) in all samples of muscle
from the 10x dose group; muscle samples from the 1x and 3x dose groups were not analyzed.

Residues of CGA179500 were als o below the LOQ ( <0.01 ppm) in fat and liver samples from
the 3x dose group, but were ab ove the LOQ in fat samples (0.02

- 0.03 ppm) and liver samples

(0.01

- 0.02 ppm) from the high

- dose group. Fat and liver samples from the 1x dose group were
not analyzed. Residues of CGA179500 were above the LOQ in kidney samples from the low

dose (0.05

- 0.08 ppm), mid

- dose (0.04

- 0.05 ppm), and high

- dose (0.40

- 0.54 ppm) groups.

A summary of residue data from the poultry feeding study with trinexapac

- ethyl is presented in

T able 14

.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 31 of 70 Table 14

. Summary of Residue Data from Poultry Feeding Study with CGA179500.

Matrix Feeding Level
(ppm) Residue Levels (ppm)

n Min. Max. Median Mean Std.

Dev.

Egg 1 9.9 (3X) 3 <0.01 <0.01 <0.01 <0.01 NA

33.3 (10X) 3 <0.01 <0.01 <0.01 < 0.01 NA

33.3 (10X) 3 0.01 0.01 0.01 0.01 NA

Fat 9.9 (3X) 3 <0.01 <0.01 <0.01 <0.01 NA

33.3 (10X) 3 0.02 0.03 0.03 0.03 0.0

Liver 9.9 (3X) 3 <0.01 <0.01 <0.01 <0.01 NA

33.3 (10X) 3 0.01 0.02 0.02 0.02 0.0

Kidney 3.3 (1X) 3 0.05 0.08 0.06 0.06 0.0

9.9 (3X) 3 0.04 0.05 0.04 0.04 0.0

33.3 (10X) 3 0.40 0.54 0.42 0.45 0.1

Muscle 33.3 (10X) 3 <0.01 <0.01 <0.01 <0.01 NA

1 Summary of residue data from e ach day of collection (0,1,3,7,10,14,17,21,24,and 28 [3X only]). The second 10X line

represents summary data from day 28.



### Expected secondary residues in meat and eggs

To determine the need for tolerances for residues trinexapac

- ethyl as CGA179500 in eggs and
tissues, the anticipated secondary residues in hen matrices were estimated using transfer

c oefficient factors calculated from the maximum residues of CGA179500 observed at the dose

level closest to the RBDB in the poultry feeding study. The transfer coefficients (calculated as
residue level to feed level ratios) are presented in Table 15 . The transfer coefficient for each

matrix was then used to calculate the expected secondary residues by multiplying the transfer
coefficient by the calculated dietary burden. The expected residues of CGA179500 and the
recommended tolerances based on expected r esidues are presented in Table 1 6

.

Table 1 5 . Residue

- Level

- to

- Feed Ratios (Transfer Coefficients) in Poultry Egg a nd Tissues.

Matrix Maximum Residue of

CGA179500 (ppm) Feeding Level
(ppm) Transfer

Coefficient 1

Egg <0.01 10 0.0010

Fat <0.01 10 0.0010

Liver <0.01 10 0.0010

Kidney 0.08 3. 7 0.02 16

Muscle <0.01 37 0.000 3

1 Calculated from the maximum residues observed at the dose level closest to the RBDB divided by the dose level.

Table 1 6 . Expected Secondary Residues of CGA179500 in Meat and Egg

. Matrix Dietary Burden
(ppm) Secondary Residues 1

(ppm) Recommended Tolerance
(ppm)

Egg 3.00 0.003 Not required

Fat 3.00 0.003 Not required

Liver 3.00 0.003 Not required

Kidney 3.00 0.0 65 Not required

Muscle 3.00 0.001 Not required

1 Calculated from dietary burden x transfer coefficient from Table 15

.



### HED Conclusions

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 32 of 70 T he trinexapac

- ethyl as CGA179500 residue data from the poultry feeding study is adequate to
satisfy data requirements. Based on the transfer coefficients for hen ti ssues and the relatively

low dietary burden for poultry of 3.00 ppm for CGA179500, no tolerances are needed for
poultry . Although secondary residues occur in poultry kidney, no tolerance is required since
poultry kidney is not considered a commodity used as human food [OPPTS 860.1480(d)(4)(iv)]

.

860.1500 Crop Field Trials

DER Reference s: 4 8043603 .der1 ( barley )

, 4 8043601 .der1 ( wheat )

, 4 8043602 .der1 (sugarcane)

, 48043701.der (grass grown for seed) , 45898901.der ( 2001 trials; grass grown for seed)

, 46809305.der ( 2004 trials; grass grown for seed)

,



### Syngenta Crop Protection, Inc. has submitted field trial data on barley, wheat, sugarcane , and
grasses grown for seed supporting the proposed uses of trinexapac

- ethyl ( EC)

. The resu lts from

these field trials discussed below and the residue data are summarized in Table 1 7

.

Table 1 7 . Summary of Residue Data from Crop Field Trials with Trinexapac

- ethyl as CGA179500

Commodity Analyte Total Applic.

Rate

(lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Min. Max. HAFT Mean Std.

Dev.

Barley (proposed use = 0. 11 lb ai/A total application rate, 45

- day PHI)

Barley, hay CGA179500 0.113

- 0.119 30 24 <0.01 0.54 0.48 0.19 0.1

Barley, straw CGA179500 0.114

- 0.120 45 24 <0.01 0.29 0.24 0.11 0.1

Barley, grain CGA179500 0.114

- 0.120 45 24 <0.01 1.3 1.2 0.59 0.3

Wheat (proposed use = 0.1 1 l b ai/A total application rate, 4 5

- day PHI)

Wheat, forage CGA179500 0.114

- 0.120 30 40 <0.01 0.98 0.94 0.16 0.2

Wheat, hay CGA179500 0.114

- 0.120 30 39 <0.01 1.3 1.2 0.27 0.3

Wheat, straw CGA179500 0.113

- 0.120 45 40 <0.01 0.64 0.60 0.19 0.2

Wheat, grain CGA179500 0.113

- 0.120 45 39 3 0.07 4.0 3.3 0.73 0.7

Sugarcane (proposed use = 0.31 lb ai/A total application rate, 28

- day PHI)

Sugarcane CGA179500 0.313

- 0.341 28 16 <0.01 0.43 0.41 0.16 0.1

Grass grown for seed (proposed use = 0.5 lb ai/A total application rate, 35

- day PHI for mature grass and 49

- day PHI for
regrowth of forage and hay following harvest)

Grass, forage CGA179500 0.505

- 0.537 49 24 0.031 1.2 0.88 0.24 0.3

Grass, hay CGA179500 0.505

- 0.537 49 22 0.10 3.4 2.6 0.65 0.8

Grass, straw CGA179500 0.505

- 0.537 35 24 0.19 5.7 5.4 2.0 2

Grass, seed
screenings CGA179500 0.505

- 0.537 35 22 0.32 20.0 18.3 6.5 7

1 The LOQ is 0.010 ppm.



### Barley

Syngenta Crop Protection, Inc. submitted field trial data from trials comparing trinexapac

- ethyl

as CGA179500 residues in/on barley (hay, straw, and grain) following application of an

emulsifiable concentrate (EC) formulation containing 2.1 lb ai/gal (trin exapac

- ethyl 250EC).
Twelve barley field trials were conducted during 2008 in NAFTA Zones 1 (PA; 1 trial), 5 (IA,

WI, ND; 3 trials), 7 (ND; 4 trials), 9 (CO; 1 trial), 10 (CA; 1 trial), and 11 (OR, ID; 2 trials).

E ach field trial included one treated plo t in which trinexapac

- ethyl was applied to barley as a
foliar spray application at a target rate of 0.115 lb ai/A (~1x the proposed maximum seasonal

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 33 of 70 rate of 0.11 lb ai/A) . Single control and duplicate treated samples of barley hay were harvested

from each plot 30 days PHI and barley straw and grain samples were harvested at 45 days PHI.

Barley samples were analyzed for residues of trinexapac

- ethyl as CGA179500 using a method
utilizing a liquid chromatographic system with tandem mass spectrometers (LC/MS/M S). The

method was adequately validated prior to and in conjunction with the analysis of the field trial
samples, using untreated samples fortified separately with CGA179500 at 0.01, 0.10 and 1.0

- 11.0 ppm. The validated LOQ was 0.01 ppm for CGA179500.

The maximum storage duration from harvest to extraction for analysis was 2.6

- 15.1 months for
barley hay, 2.1

- 13.4 months for barley straw, and 2.2

- 16.1 months for barley grain. Storage

stability data have not been submitted for barley; however, acceptabl e storage stability data are
available for wheat (grain and straw) and rapeseed pending submission of a copy of the

anal ytical method used in the study.

Following a foliar spray application of trinexapac

- ethyl at a total rate of 0.113

- 0.120 lb ai/A,

CGA1 79500 residues were <0.01

- 0.54 ppm in/on barley hay, <0.01

- 0.29 ppm in/on barley straw,

and <0.01

- 1.3 ppm in/on barley grain at PHIs of 30 (hay) or 45 days (straw and grain).

In the residue decline trial, CGA179500 residues generally declined steadily a t longer post

treatment intervals in/on barley hay and straw. For barley grain, residues were relatively
consistent at each post

- treatment interval. For barley hay, CGA179500 residues declined from
6.73 ppm at 0 days PHI to 0.317 ppm by 37 days PHI. For barley straw, CGA179500 residues

declined from 0.275 ppm at 24 days PHI to 0.131 ppm by 52 days PHI. For barley grain,
CGA179500 residues increased from 0.967 ppm at 24 days PHI to 1.3 ppm by 31 days PHI,
declined to 0.727 ppm by 38 days PHI, and then in creased to 0.992 ppm by 52 days PHI.

HED Conclusions

The submitted residue data for barley commodities (hay, straw, and grain) are adequate to satisfy
data requirements. Geographic representation of data is adequate; the location and number of

f ield tri als are in compliance with OPPTS Guideline 860.1500 . The trials reflect the proposed

use pattern. The data were generated using a validated analytical method and are supported by
adequate storage stability data.

The residue data for barley hay, straw, and grain were entered into the Agency’s OECD

calculator to determine appropriate tolerance levels; see Appendix II. The tolerance spreadsheet

recommends tolerances of 0.8

, 0.4 , and 2.0 ppm for residues of CGA179500 in/on barley hay,

straw, and grain, respectively.

Wheat

Syngenta Crop Protection, Inc. submitted field trial data from trials comparing trinexapac

- ethyl

as CGA179500 residues in/on wheat (forage, hay, straw, and grain) f ollowing application of an

emulsifiable concentrate (EC) formulation containing 2.1 lb ai/gal (trinexapac

- ethyl 250EC).

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 34 of 70 Twenty wheat field trials were conducted during 2007

- 2008 in NAFTA Zones 2 (VA; 1 trial), 4

(AR; 1 trial), 5 (KS, ND, MN, MO, IN; 5 tri als), 6 (OK; 1 trial), 7 (ND, SD, NE; 5 trials), 8 (TX,

OK; 6 trials), and 11 (ID; 1 trial). E ach field trial included one treated plot in which trinexapac

ethyl was applied to wheat as a foliar spray application at a target rate of 0.115 lb ai/A (~1x the
proposed maximum seasonal rate of 0.11 lb ai/A) . Single control and duplicate treated samples

of wheat forage and hay were harvested from each plot 30 days PHI and wheat straw and grain
were harvested at 45 days PHI.

Wheat samples were analyzed for resi dues of trinexapac

- ethyl as CGA179500 using a method
utilizing a liquid chromatographic system with tandem mass spectrometers (LC/MS/MS). The
method was adequately validated in conjunction with the analysis of the field trial samples, using

untreated samp les fortified separately with CGA179500 at 0.01, 0.10 and 1.0

- 15.0 ppm. The

validated LOQ was 0.01 ppm for CGA179500.

The maximum storage duration from harvest to extraction for analysis was 11.6

- 16.0 months for
wheat forage, 11.5

- 15.1 months for wheat hay, 8.9

- 13.8 months for wheat straw, and 9.8

- 17.1
months for wheat grain. Adequate storage stability data are available pending submission of a

copy of the analytical method used in the study (refer to 45898903.der ) . T he available storage
stability dat a indicate that residues of CGA179500 are stable in/on frozen wheat (grain) for up to

24 months and frozen wheat (straw) for up to 12 months

.

Following a foliar spray application of trinexapac

- ethyl at a total rate of 0.113

- 0.120 lb ai/A,

CGA179500 residues were <0.01

- 0.98 ppm in/on wheat forage, <0.01

- 1.3 ppm in/on wheat hay,

<0.01

- 0.64 ppm in/on wheat straw, and 0.07

- 4.0 ppm in/on wheat grain at PHIs of 30 (forage and
hay) or 45 days (straw and grain).

In the residue decline trials, CGA179500 residues generally declined steadily at longer post

treatment intervals in/on wheat forage, hay, straw, and grain. Residues generally decreased until
the last sampling interval in which a slight increase was observed. For wheat forage,

CGA179500 residues declined from 2.1

- 5.6 ppm at 0 days PHI to 0.04

- 0.12 ppm by 37 days
PHI. For wheat hay, CGA179500 residues declined from 1.3

- 11 ppm at 0 days PHI to 0.09

- 0.15
ppm by 37 days PHI. For wheat straw, CGA179500 residues declined from <0.01

- 0.24 ppm at

31 days PHI to 0.08

- 0.12 ppm by 52 days PHI. For wheat grain, CGA179500 residues declined

from 0.33

- 0.69 ppm at 31 days PHI to 0.24

- 0.70 ppm by 52 days PHI.

HED Conclusions :

T he submitted residue data for wheat commodities (forage, hay, straw, and grain) are adequate to satisfy data requirements pending adjustment of tolerance levels for certain commodities.
Geographic representation of data is adequate; the location and number of f ield trials are in
compliance with OPPTS Guideline 860.1500 . The trials reflect the proposed use pattern. The

data were generated using a validated analytical method and are suppor ted by adequate storage
stability data.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 35 of 70 The residue data for wheat forage, hay, straw, and grain were entered into the OECD calculator
to determine appropriate tolerance levels; see Appendix II. The tolerance spreadsheet

recommends tolerances of 1.0

, 1 .5

, 0.9 , and 4.0 ppm for residues of CGA179500 in/on wheat
forage, hay, straw, and grain, respectively.

Sugarcane

Syngenta Crop Protection, Inc. submitted field trial data from trials comparing trinexapac

- ethyl

as CGA179500 residues in/on sugarcane following application of an emulsifiable concentrate
(EC) formulation containing 2.1 lb ai/gal (trinexapac

- ethyl 250EC). Eight sugarcane field trials
were conducted during 2007

- 2008 in NAFTA Zones 3 (FL; 3 trials), 4 (LA; 3 trials), 6 (TX; 1

trial), and 13 (HI; 1 trial). E ach field trial included one treated plot in which trinexapac

- ethyl
was applied to sugarcane as a sing le foliar spray application at a target rate of 0.312 lb ai/A (1x
the proposed maximum seasonal rate of 0.31 lb ai/A) . Single control and duplicate treated

samples of sugarcane were harvested from each plot 28 days PHI.

Sugarcane samples were analyzed fo r residues of trinexapac

- ethyl as CGA179500 using a

modified method utilizing a liquid chromatographic system with tandem mass spectrometers
(LC/MS/MS). The method was adequately validated prior to and in conjunction with the
analysis of the field trial s amples, using untreated samples fortified separately with CGA179500

at 0.01, 0.10 and 10 ppm. The validated LOQ was 0.01 ppm for CGA179500.

The maximum storage duration from harvest to extraction for analysis was 14.6

- 22.2 months for

sugarcane. No stora ge stability data for CGA179500 in/on sugarcane were submitted. However,
adequate storage stability data are available for grass, wheat and rapeseed pending submission of
a copy of the analytical method used in the study (refer to 45898903.der ) . T he avai lable storage

stability data indicate that residues of CGA179500 are stable in/on frozen wheat (grain) for up to

24 months and frozen wheat (straw)

, rapeseed for up to 12 months and grass for up to 9 months

.

Following a single foliar spray application o f trinexapac

- ethyl at a total rate of 0.313

- 0.341 lb

ai/A, CGA179500 residues were <0.01

- 0.43 ppm in/on sugarcane at 28 days PHI. Average
residues in/on sugarcane were 0.16 ppm.

In the Belle Glade, FL residue decline trial, CGA179500 residues generally declined steadily at
longer post

- treatment intervals in/on sugarcane. CGA179500 residues increased from <0.01

ppm at 0 days PHI to 0.0650 ppm by 14 days PHI then declined to 0.0287 ppm by 35 days PHI.
In the Washington, LA residue decline trial, CGA179500 residues declined steadily at longer

post

- treatment intervals in/on sugarcane. CGA179500 residues declined from 0.357 ppm at 0

days PHI to 0.233 ppm by 35 days PHI.

HED Conclusions

The submitted re sidue data for sugarcane are adequate to satisfy data requirements. Geographic
representation of data is adequate; the location and number of field trials are in compliance with

OPPTS Guideline 860.1500. The trials reflect the proposed use pattern. The d ata were generated
using a validated analytical method and are supported by adequate storage stability data.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 36 of 70 The residue data for sugarcane were entered into the Agency’s OECD calculator to determine
appropriate tolerance levels ; see Appendix II. The tolerance spreadsheet recommends a

tolerance of 0.8 ppm for residues of CGA179500 in/on sugarcane.

Grass, grown for seed

Syngenta has submitted two sets of field trials supporting the use of trinexapac

- ethyl on grasses
grown for seed. The original five field trials supporting the 45

- day PHI were conducted in 2001

in the Pacific Northwest ( 45898901.der ), and the more recent field trials supporting the 35

- day
PHI were conducted in 2004 in Regions 4, 10, 11, and 12 (46809305.der)

. Residues of free
trinexapac in/on grass commodities were determined using the HPLC/MS method (Syngenta

Method 110

- 01), which was adequately validated in conjunction with the analysis o f field trial
samples. The LOQ is 0.05 ppm for trinexapac in each gras s commodity, and LOD was not
reported.

Syngenta submitted field trial data from trials comparing trinexapac

- ethyl as CGA179500
residues in/on grass (forage regrowth, hay regrowth, straw, and seed screenings) following

application of an emulsifiable concen trate (EC) formulation containing 2.1 lb ai/gal (trinexapac

ethyl 250EC). Twelve grass field trials were conducted during 2008 in NAFTA Zones 5 (MO,

IA, MN; 4 trials), 10 (CA; 2 trials), 11 (WA; 2 trials), and 12 (OR; 4 trials). E ach field trial

included one treated plot in which trinexapac

- ethyl was applied to grass grown for seed as a
foliar spray application at a target rate of 0.525 lb ai/A (~1x the proposed maximum seasonal

rate of 0.5 lb ai/A) . Single control and duplicate treated samples of grass seed and straw were

harvested from each plot 35 days PHI and grass regrowth forage and hay were harvested at 49
days PHI.

Grass samples were analyzed for residues of trinexapac

- ethyl as CGA179500 using a method
utilizing a liquid chromatographic system wi th tandem mass spectrometers (LC/MS/MS). The
method was adequately validated in conjunction with the analysis of the field trial samples, using

untreated samples fortified separately with CGA179500 at 0.01, 0.10 and 2.0

- 25.0 ppm. The

validated LOQ was 0. 01 ppm for CGA179500. The validated LOQ was 0.01 ppm for
CGA163935 and 0.05 ppm for CGA179500.

The maximum storage duration from harvest to extraction for analysis was 9.8

- 17.1 months for
grass seed screenings, 7.3

- 10.9 months for grass straw, 8.4

- 10.1 months for grass forage

regrowth, and 6.8

- 9.9 months for grass hay regrowth . T he submitted storage stability data
indicate that residues of CGA179500 are stable in/on frozen grass (clippings) for up to 6 months

and residues of CGA179500 are stable in/on frozen grass (thatch + sod) for up to 9 months (refer

to 47101601.der). These data are not adequate to support the sample storage durations for
samples of grass for CGA179500. However, adequate storage stability dat a are available for
wheat (grain and straw) and rapeseed pending submission of a copy of the anal ytical method

used in the study

.

Following a foliar spray application of trinexapac

- ethyl at a total rate of 0.505

- 0.537 lb ai/A,

CGA179500 residues were 0. 031

- 1.2 ppm in/on grass forage regrowth, 0.10

- 3.4 ppm in/on grass
hay regrowth, 0.19

- 5.7 ppm in/on grass straw, and 0.32

- 20 ppm in/on grass seed screenings at

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 37 of 70 PHIs of 35 (seed screenings and straw) or 49 days (forage and hay regrowth).

HED Conclusions

The submitted residue data for grass commodities (forage, hay, straw, and seed screenings) are adequate to satisfy data requirements

. The original five field trials supporting the 45

- day PHI

conducted in 2001 in the Pacific Northwest ( 45898901.der ) do not support the new labels for

the35

- day PHI for grass and t he field trials supporting the 35

- day PHI conducted in 2004

(46809305.der) were not included in the OECD calculator due to the older method (Syngenta

Method 110

- 01). The newer method GRM020.10A inclu des a strong acid hydrolysis/extraction
procedure to release both “free” and “conjugated” residues of CGA 179500 from field grown

grass.

The residue data for grass forage, hay, straw, and seed screenings were entered into the Agency’s

OECD calculator to determine appropriate tolerance levels; see Appendix II

. The tolerance
spreadsheet recommends tolerances of 1. 5 , 4.0, 10 , and 4 0 ppm for residues of CGA179500
in/on grass forage, hay, straw, and seed screenings, respectively.

860.1520 Processed Food and Feed

DER Reference s: 48043603.der2 (barley)

, 48043601.der2 (wheat)

, 48043602.der2 (sugarcane)



### Barley

Syngenta Crop Protection, Inc. submitted a processing study for trinexapac

- ethyl on barley. In
two crop field trials conducted in ND, trinexapac

- ethyl, formulated as an emulsifiable

concentrate (EC), was applied to barley at the label rate (0.115 lb ai/A) and at the exaggerated
rate (5x) of 0.575 lb ai/A. Barley grain was harvested at 45 days PHI and processed into pearled
barley, flour , and bran by GLP Technologies (Navasota, TX) using simulated commercial

procedures. Adequate descriptions were provided of the processing procedures, including

material balance summaries.

Residues of trinexapac

- ethyl as CGA179500 were determined using m odified analytical method

GRM020.01A, using high performance liquid chromatography with triple quadrupole mass
spectrometric detection (LC

- MS/MS)

. The LOQ was 0.01 ppm for CGA179500. The method is
adequate for data collection based on acceptable concurrent method recovery data.

The maximum storage duration from harvest/processing to extraction for analysis was 353

- 379
days (11.6

- 12.5 months) for barley gr ain and 335

- 350 days (11.0

- 11.5 months) for pearled

barley, 331

- 346 days (10.9

- 11.4 months) for barley flour, and 334

- 349 days (11.0

- 11.5 months)
for barley bran. Analysis took place between 0 and 6 days after extraction. N o storage stability

data are av ailable for CGA179500 for barley grain (RAC) and barley processed fractions.

However, adequate storage stability data are available wheat (grain and straw) and rapeseed
pending submission of a copy of the analytical method used in the study . T he availabl e storage stability data indicate that residues of CGA179500 are stable in/on frozen wheat (grain) for up to

24 months and frozen wheat (straw) and rapeseed for up to 12 months.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 38 of 70 A summary of residue data from the barley processing study is presented in Table 1 8

. C GA179500 residues in/on barley RAC samples collected for 1x processing were 0.510

- 0.750
ppm (average). Average CGA179500 residues were 0.748

- 0.856 ppm in/on pearled barley,

0.209

- 0.286 ppm in/on barley flour, and 1.04

- 1.32 ppm in/on barley bra n.

CGA179500 residues in/on barley RAC samples collected for 5x process ing were 5.58

- 6.73

ppm . Average CGA179500 residues were 4.84

- 9.34 ppm in/on pearled barley, 1.40

- 4.15 ppm

in/on barley flour, and 9.84

- 10.9 ppm in/on barley bran.

A comparison of th e CGA179500 residues in the raw agricultural commodity (RAC) with those

in each 1x processed fraction resulted in mean concentration factors 1.1

- 1.5x in pearled barley,

0.3

- 0.6x in barley flour, and 1.8

- 2.0x in barley bran.

A comparison of the CGA179500 residues in the raw agricultural commodity (RAC) with those
in each 5x processed fraction resulted in mean concentration factors of 0.9

- 1.4x in pearled
barley, 0.3

- 0.6x in barley flour, and 1.6

- 1.8x in barley bran.

The theoretical concentration factors ( based on separation of components; OPPTS 860.1520,
Table 3) are 7.7x for barley bran and 1.2x for pearled barley

. The observed concentration factors

were less than the theoretical concentration factors with the exception of pearled barley (1.4

- 1.5x) at bo th application rates in the ND trial.

Table 1 8

. Residue Data from Barley Processing Studies with Trinexapac

- ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) PHI

(days) Residues

(ppm) Processing

Factor 1

Northwood, ND; 2008 (C13ND081704 ) 1x

Barley Grain (RAC) 0.115 45 0.503

0.550

0.477 --

Pearled barley 0.115 45 0.778

0.718 2 1.5x

Flour 0.115 45 0.260

0.312 2 0.6x

Bran 0.115 45 0.950

1.12 2 2.0x

Carrington, ND; 2008 (C13ND081705) 1x

Barley Grain (RAC) 0.115 45 0.654

0.842

0.755 --

Pearled barley 0.115 45 0.819

0.892 2 1.1x

Flour 0.115 45 0.235

0.182 2 0.3x

Bran 0.115 45 1.38

1.26 2 1.8x

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 39 of 70 Table 1 8

. Residue Data from Barley Processing Studies with Trinexapac

- ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) PHI

(days) Residues

(ppm) Processing

Factor 1

Northwood, ND; 2008 (C13ND081704 ) 5x

Barley Grain (RAC) 0.578 45 9.13

5.20

5.86 --

Pearled barley 0.578 45 10.1

8.58 2 1.4x

Flour 0.578 45 4.60

3.70 2 0.6x

Bran 0.578 45 10.8

10.9 2 1.6x

Carrington, ND; 2008 (C13ND081705) 5x

Barley Grain (RAC) 0.575 45 5.23

5.40

6.10 --

Pearled barley 0.575 45 5.54

4.13 2 0.9x

Flour 0.575 45 1.40

1.40 2 0.3x

Bran 0.575 45 10.1

9.58 2 1.8x

1 Mean Processing factors were calculated by the reviewer using the equation: Processing Factor = [Mean Measured residue for

analyte in the processed fraction] / [Mean Measured residue for analyte in the RAC].

2 Repeat analysis.



### HED Conclusions

Processin g of the RAC with quantifiable residues of CGA179500 resulted in the concentration of

residues in certain barley fractions but not in others (range of average processing factors
provided in parenthesis). Residues concentrated in pearled barley (0.9

- 1.5x ; average 1.2x ) and

bran (1.6

- 2.0x ; average 1.8x ) and did not concentrate in flour (0.3

- 0.6x ; average 0.5x ). These

data suggest that a tolerance is needed for barley bran but not for pearled barley . The maximum
expected residue of CGA179500 in bran

, resulting from the proposed use is 2.2 ppm. This value
was calculated by multiplying the average concentration factor of 1.8 x by the HAFT residue of

1.2 ppm

.

Based on this determination, the petitioner is required to submit a revised Section F to propose a

tolerance of 2. 5 ppm (rounded up) for residues of CGA179500 in/on “ barley bran .” A tolerance

for pearled barley is not needed because the maximum expected residues of 1.4 ppm (CF of 1. 2 x

HAFT of 1.2 ppm) will be covered by HED recommended tolerance of 2.0 ppm for barley grain

.

Sugarcane

Syngenta Crop Protection, Inc. submitted a processing study for trinexapac

- ethyl on sugarcane.
In two crop field trials conducted in FL and LA, trinexapac

- ethyl, formulated as an emulsifiable

concentrate (EC), was applied to sugarcane at the label rate (0.312 lb ai/A) and at the

exaggerated rate (5x) of 1.56 lb ai/A. Sugarcane was harvested at 28 days PHI and processed
into molasses and refined sugar by GLP Technologies (Navasota, TX) using simulated
commercial pro cedures. Adequate descriptions were provided of the processing procedures,

including material balance summaries.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 40 of 70 Residues of trinexapac

- ethyl as CGA179500 were determined using modified analytical method

GRM020.01A, using high performance liquid chromato graphy with triple quadrupole mass
spectrometric detection (LC

- MS/MS)

. The LOQ was 0.01 ppm for CGA179500. The method is
adequate for data collection based on acceptable concurrent method recovery data.

The maximum storage duration from harvest/processi ng to extraction for analysis was 457

- 658
days (15.0

- 21.6 months) for sugarcane, 439

- 535 days (14.4

- 17.6 months) for molasses, and 438

- 534 days (14.4

- 17.6 months) for refined sugar. Analysis took place between 0 and 4 days after

extraction. N o storage st ability data are available for CGA179500 for sugarcane (RAC) and
processed fractions. However, adequate storage stability data are available wheat (grain and

straw) and rapeseed pending submission of a copy of the analytical method used in the study

(refe r to 45898903.der, previously reviewed) . T he available storage stability data indicate that
residues of CGA179500 are stable in/on frozen wheat (grain) for up to 24 months

, frozen wheat

(straw) and rapeseed for up to 12 months

. , and grass for up to 9 mont hs.

A summary of residue data from the sugarcane processing study is presented in Table 19

. Average CGA179500 residues in/on sugarcane RAC samples collected for 1x processing were

0.054

- 0.211 ppm. Average CGA179500 residues were 0.323

- 1.425 ppm in/on molasses and

<0.01

- 0.027 ppm in/on refined sugar.

Average CGA179500 residues in/on sugarcane RAC samples collected for 5x processing were

0.282

- 2.47 ppm. Average CGA179500 residues were 1.74

- 10.9 ppm in/on molasses and <0.01

- 0.232 ppm in/on refined suga r.

A comparison of the CGA179500 residues in the raw agricultural commodity (RAC) with those

in each 1x processed fraction resulted in mean concentration factors of 6.0

- 6.7x in molasses and

0.13

- 0.19x in refined sugar.

A comparison of the CGA179500 residues in the raw agricultural commodity (RAC) with those
in each 5x processed fraction resulted in mean concentration factors of 4.4

- 6.2x in molasses and

0.04

- 0.09x in refined sugar.

All of the processing factors calculated in this study were less than the maximum theoretical
concentration factors of 11.8x for sugar (based on separation of components; OPPTS 860.1520,

Table 3) and 20x for molasses (based on the maximum observed (experimental) concentration

factor; OPPTS 860.1520, Table 4).

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 41 of 70 Table 19

. Residue Data from Sugarcane Processing Studies with Trinexapac

- ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) PHI

(days) Residues

(ppm) Processing

Factor 1

Clewiston, FL; 2007 (E19FL078492) 1x

Sugarcane Sugarcane (RAC) 0.341 28 0.0385

0.0752

0.0475 --

Molasses 0.341 28 0.323

0.322 2 6.0x

Refined Sugar 0.341 28 <LOQ

<LOQ 2 0.19x

Washington, LA; 2007 (E18LA078495) 1x

Sugarcane Sugarcane (RAC) 0.322 28 0.310

0.210

0.114 --

Molasses 0.322 28 1.57

1.28 2 6.7x

Refined Sugar 0.322 28 0.0238

0.0300 2 0.13x

Clewiston, FL; 2007 (E19FL078492) 5x

Sugarcane Sugarcane (RAC) 1.66 28 0.377

0.230

0.238 --

Molasses 1.66 28 1.70

1.77 2 6.2x

Refined Sugar 1.66 28 <LOQ

<LOQ 2 0.04x

Washington, LA; 2007 (E18LA078495) 5x

Sugarcane Sugarcane (RAC) 1.59 28 2.22

2.99

2.20 --

Molasses 1.59 28 12.6

9.23 2 4.4x

Refined Sugar 1.59 28 0.220

0.243 2 0.09x

1 Mean Processing factors were calculated by the reviewer using the equation: Processing Factor = [Mean Measured residue for
analyte in the processed fraction] / [Mean Measured residue for analyte in the RAC].

2 Repeat analysis.



### HED Conclusions

Processin g of the RAC with quantifiable residues of CGA179500 resulted in the concentration of
residues in sugarcane molasses (average processing factors 4.4

- 6.7x; average 5.8x) and did not

concentrate in refined sugar ( average processing factors 0.04

- 0.13x; averag e 0.11x). These data
suggest that a tolerance is needed for sugarcane molasses. The maximum expected residues of
CGA179500 in sugarcane molasses, resulting from the proposed use is 2.4 ppm. This value was

calculated by multiplying the average concentrat ion factor of 5.8x by the HAFT residue of 0.41

ppm

.

Based on this determination, the petitioner is required to submit a revised Section F to propose a

tolerance of 2. 5 ppm (rounded up) for residues of CGA179500 in/on “sugarcane

, molasses .”

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 42 of 70 Wheat

Synge nta Crop Protection, Inc. submitted a processing study for trinexapac

- ethyl on wheat. In
two crop field trials conducted in ND and TX, trinexapac

- ethyl, formulated as an emulsifiable
concentrate (EC), was applied to wheat at the label rate (0.115 lb ai/A) and at the exaggerated

rate (5x) of 0.575 lb ai/A. Wheat grain was harvested at 45 days PHI and processed into
aspirated grain fractions (AGF), bran, flour, middlings, shorts, and germ by GLP Technologies
(Navasota, TX) using simulated commercial procedu res. Adequate descriptions were provided

of the processing procedures, including material balance summaries.

Residues of trinexapac

- ethyl as CGA179500 were determined using analytical method

GRM020.01A, using high performance liquid chromatography with triple quadrupole mass
spectrometric detection (HPLC

- MS/MS)

. The limit of quantitation (LOQ) was 0.01 ppm for
CGA179500. The method is adequate for data collection based on acceptable concurrent method

recovery data.

The maximum storage duration from ha rvest/processing to extraction for analysis was 341

- 416

days (11.2

- 13.7 months) for wheat grain and 334

- 384 days (11.0

- 12.6 months) for AGF, 280

- 474
days (9.2

- 15.6 months) for bran, 335

- 385 days (11.0

- 12.7 months) for flour, 235

- 471 days (7.7

- 15.5 months) for middlings, 236

- 470 days (7.8

- 15.5 months) for shorts, and 237

- 469 days (7.8

- 15.4 months) for germ. Analysis took place between 1 and 6 days after extraction. T he available
storage stability data indicate that residues of CGA179500 are stable in/on fr ozen wheat (grain)
for up to 742 days (refer to 4 5898903.der ).

A summary of residue data from the wheat processing study is presented in Table 20

. Average
CGA179500 residues in/on wheat RAC samples collected for 1x processing were 0.304

- 1.65

ppm. Aver age CGA179500 residues were 0.235

- 0.345 ppm in/on wheat AGF, 0.659

- 3.46 ppm

in/on wheat bran, 0.132

- 0.741 ppm in/on wheat flour, 0.557

- 3.45 ppm in/on wheat middlings,

0.181

- 1.01 ppm in/on wheat shorts, and 0.149

- 0.420 ppm in/on wheat germ.

Average CGA179 500 residues in/on wheat RAC samples collected for 5x processing were 5.40

- 9.75 ppm. Average CGA179500 residues were 3.49

- 4.40 ppm in/on wheat AGF, 8.59

- 14.7 ppm

in/on wheat bran, 2.65

- 3.74 ppm in/on wheat flour, 2.53

- 5.39 ppm in/on wheat middlings, 0.154

- 5.70 ppm in/on wheat shorts, and 5.09

- 10.83 ppm in/on wheat germ.

A comparison of the CGA179500 residues in the raw agricultural commodity (RAC) with those
in each 1x processed fraction resulted in mean processing factors of 0.21

- 0.77x in wheat AGF,

2.09

- 2.17x in wheat bran, 0.43

- 0.45x in wheat flour, 0.34

- 11.3x in wheat middlings, 0.59

- 0.61x

in wheat shorts, and 0.91

- 1.38x in wheat germ.

A comparison of the CGA179500 residues in the raw agricultural commodity (RAC) with those

in each 5x processed fraction resulted in mean processing factors of 0.36

- 0.81x in wheat AGF,

1.50

- 1.59x in wheat bran, 0.38

- 0.49x in wheat flour, 0.47

- 0.55x in wheat middlings, 0.03

- 0.58x

in wheat shorts, and 0.94

- 1.11x in wheat germ.

The theoretical concentration factors (based on separation of components; OPPTS 860.1520,

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 43 of 70 Table 3) are 7.7x for wheat bran, 1.4x for wheat flour, and 8.3x for shorts. The observed
concentration factors were less than the theoretical concentration factors with the exception of

middlings (11.3x) at the 1x rate in the ND trial.

Table 20

. Residue Data from Wheat Proce ssing Studies with Trinexapac

- ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) PHI

(days) Residues

(ppm) Processing

Factor 1

Carrington, ND; 2008 (C13ND078468) 1x

Wheat Grain (RAC) 0.115 45 0.328

0.308

0.277 --

AGF 0.115 45 0.240

0.230 2 0.77x

Bran 0.115 45 0.611

0.707 2 2.17x

Flour 0.115 45 0.155

0.108 2 0.43x

Middlings 0.115 45 3.67

3.29 2

3.39 2 11.3x

Shorts 0.115 45 0.150

0.195 2

0.197 2 0.59x

Germ 0.115 45 0.598

0.310 2

0.352 2 1.38x

Groom, TX; 2007 (W01TX078473) 1x

Wheat Grain (RAC) 0.116 45 1.75

1.66

1.54 --

AGF 0.116 45 0.350

0.340 2 0.21x

Bran 0.116 45 2.28

4.63 2 2.09x

Flour 0.116 45 0.900

0.582 2 0.45x

Middlings 0.116 45 0.820

0.422 2

0.429 2 0.34x

Shorts 0.116 45 0.925

1.15 2

0.948 2 0.61x

Germ 0.116 45 1.62

1.52 2

1.34 2 0.91x

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 44 of 70 Table 20

. Residue Data from Wheat Proce ssing Studies with Trinexapac

- ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) PHI

(days) Residues

(ppm) Processing

Factor 1

Carrington, ND; 2008 (C13ND078468) 5x

Wheat Grain (RAC) 0.576 45 5.57

4.90

5.73 --

AGF 0.576 45 4.77

4.03 2 0.81x

Bran 0.576 45 7.85

9.33 2 1.59x

Flour 0.576 45 2.42

2.88 2 0.49x

Middlings 0.576 45 2.83

2.45 2

2.31 2 0.47x

Shorts 0.576 45 0.124

0.172 2

0.167 2 0.03x

Germ 0.576 45 5.88

4.28 2

5.11 2 0.94x

Groom, TX; 2007 (W01TX078473) 5x

Wheat Grain (RAC) 0.578 45 10.2

9.55

9.50 --

AGF 0.578 45 3.50

3.47 2 0.36x

Bran 0.578 45 15.8

104 2, 3

14.4 2

13.8 2 1.50x

Flour 0.578 45 3.67

3.80 2 0.38x

Middlings 0.578 45 5.73

5.48 2

4.96 2 0.55x

Shorts 0.578 45 5.23

6.25 2

5.61 2 0.58x

Germ 0.578 45 9.78

11.1 2

11.6 2 1.11x

1 Mean processing factors were calculated by the reviewer using the equation: Processing Factor = [Mean Measured residue for
analyte in the processed fraction] / [Mean Measured residue for analyte in the RAC].

2 Repeat analysis.

3 Outlier value was not use d in processing factor calculations.



### HED Conclusions

Processing of the RAC with quantifiable residues of CGA179500 resulted in the concentration of
residues in certain wheat fractions but not in others (range of average processing factors provided

in par enthesis). Residues concentrated slightly in wheat bran (1.50

- 2.17x; average 1.8x) and

germ (0.91

- 1.38x; average 1.1x). Residues did not concentrate in aspirated grain fractions (0.21

- 0.81x; average 0.54x), wheat flour (0.38

- 0.49x; average 0.44x), and sh orts (0.03

- 0.61x; average

0.45x). Residues did not concentrate in middlings at three of the trials (0.34

- 0.55x), but did
concentrate in middlings (11.3x) from the ND trial conducted at 1x. The overall average for

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 45 of 70 wheat middlings is 3.2x. These data sugg est that tolerances are needed for wheat bran and
middlings, but not for wheat germ. The maximum expected residues of CGA179500 in wheat

bran, middlings, and germ resulting from the proposed use, are 6.1 ppm, 10.4 ppm, and 3.6 ppm,
respectively. These va lues were calculated by multiplying the average concentration factor of
1.8x for bran, 3.2x for middlings, and 1.1x for germ by the HAFT r esidue of 3.3 ppm

.

Based on this determination, the petitioner is required to submit a revised Section F to propose

tolerances of 6. 0 ppm for bran and 10. 5 ppm (rounded up) for middlings for residues of

CGA179500. A tolerance is not required for wheat germ because the maximum expected
residues of 3.6 ppm for wheat germ will be covered by the HED recommended tol erance of 4.0
ppm for wheat grain.

860.1650 Submittal of Analytical Reference Standards

Analytical reference standards for trinexapac

- ethyl and trinexapac are available at the EPA
National Pesticide Standards Repository as of 12/14/2006. The reference standards were sent to the Analytical Chemistry Lab, which is located at Fort Meade, Maryland (Attention to either

Theresa Cole or Thuy Nguyen ) at the address listed below. The full 9 digit zip code is
mandatory or the mail will be returned to the registrant.

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

Fort George G. Meade, MD 20755

- 5350

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

860.1850 / 860.1900 Confined / Field Accumulation in Rotational Crops

DER Reference s: 45898909.der, 48043709.der



### In a confined rotational crop study, [ 14 

### C

- cyclohexyl]trinexapac

- ethyl (98% radiochemical purity)
was applied to an outdoor plot of sandy loam soil at a rate of 0.134 lb ai/A (0.3x rate; 0.15 kg
ai/ha; MRID 45898909). Rotational crops of lettuce, winter wheat, sugar beets, and corn were

planted at 69, 119, 299 and 338 DAT, respectively. S amples of immature and mature lettuce

were collected at 30 and 50 days after plantin g ( DAP )

. The confined rotati onal crop study is not
adequate as the use rate in the current study was only 0.25x the proposed use rate for grass ( 0.52

lb ai/A )

. In addition, no rotational crops were planted at a label

- specified 30

- day PBI, and only

one of the required representative crops (leaf vegetable) was planted at the minimum 69

- day PBI
tested in the study. The minimum PBI tested for the representative cereal grain was

a pproximately 4 months, and the minimum PBI tested for the representative root cr op was approximately 10 months.

In another study (MRID 48043709), s andy 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 (0.3 33

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

-

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 46 of 70 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.

Total radioactive residues (TRRs) were determined by combustion/liquid scintillation counting

(LSC) analysis of homogenized samples and also by summation of the radioactivity in the
extracts and combusted post

- extraction solids (PES), except in samples which did not require
further characterization due to low TRR (<0.01 ppm). TRR values in all RACs were low; only

30

- day PBI lettuce, wheat forage and wheat hay samples had TRR >0.01 ppm. The maximum

TRR was 0.017 ppm (30

- day PBI mature lettuce).

Further extraction and analysis was carried out for lettuce (30

- day PBI samples only) and wheat

(30

- day PBI forage and hay samples and 120

- day PBI forage, hay, and gra in samples). No
extractions were conducted with radish matrices or any 270

- day PBI lettuce or wheat matrix due

to the low TRR levels. The characterization and identification of residues in the rotational crop

lettuce and wheat ma trices is summarized in Table s 21 a and 21b

.

TABLE 2 1 a . Summary of Characterization and Identification of Radioactive Residues in
Rotational Crop Lettuce Following Application of Radiolabeled Trinexapac

- ethyl at a
Nominal Rate of 350 g ai/ha. 1, 2

Metabolite 30 DAT PBI

Lettuce, immature Lettuce, mature

TRR=0.011 ppm 1 TRR=0.017 ppm 1

%TRR ppm %TRR ppm

Unknowns 27.3 0.003 41.2 0.007

Max other single <9.1 <0.001 <5.9 <0.001

Extraction with 0.1 M KOH 9.1 0.001 5.9 0.001

Extraction with 24% KOH 45.5 0.005 35.3 0.006

Total identified 0 0 0 0

Total characterized <91.0 <0.010 <88.3 <0.015

Total extractable <91.0 <0.010 <88.3 <0.015

Unextracted (PES) 9.1 0.001 17.6 0.003

Accountability 3 <100 <0.011 <106 <0.018

1 TRR determined by summation of radioactivity present in the extracts and debris following solvent extraction.

2 An LOQ or LOD was not reported.

3 Accountability = Total extractable + Total unextractable

.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 47 of 70 TABLE 21 b . Summary of Characterization and Identification of Radioact ive Residues in Rotational Crop

Wheat Following Application of Radiolabeled Trinexapac

- ethyl at a Nominal Rate of 350 g ai/ha. 1, 2

Metabolite 30 DAT PBI 120 DAT PBI

Wheat Forage Wheat Hay Wheat Grain Wheat Forage Wheat Hay

TRR= 0.010 ppm 1 TRR= 0.011 ppm 1 TRR= 0.0 07 ppm 1 TRR= 0.004 ppm 1 TRR= 0.00 9 ppm 1

%TRR ppm %TRR ppm %TRR ppm %TRR ppm %TRR ppm

CGA179500 20 0.002 9.1 0.001

-- -- -- -- -- -- CGA312753

-- -- 18.2 0.002

-- -- -- -- 11.1 0.001

Unknowns

-- -- -- -- 14.3 0.001 <25 <0.001 <22.2 <0.002

Max other single 10 0.001 <9.1 <0.001 <14.3 <0.001 25 0.001 <11.1 <0.001

Aqueous phase 20 0.002

Extraction with 0.1 M KOH 11.1 0.001

Extraction with 24% KOH 44.4 0.004

Total identified 20 0.002 27.3 0.003 0 0 0 0 11.1 0.001

Total characterized 30 0.003 <9.1 <0.001 <28.6 <0.002 <50 <0.002 <88.8 <0.008

Total extractable 50 0.005 <36.4 <0.004 <28.6 <0.002 <50 <0.002 <99.9 <0.009

Unextracted (PES) 50 0.005 63.6 0.007 85.7 0.006 50 0.002 11.1 0.001

Accountability 3 100 0.010 <100 <0.011 <114 <0.008 <100 <0.004 <111 <0.010

1 TRR determined by summation of radioactivity present in the extracts and debris following solvent extraction.

2 An LOQ or LOD was not reported.

3 Accountability = Total extractable + Total unextractable

.



### HED Conclusions

The submitted confined rotational crop study is adequate to satisfy data requirements. TRR
values in all RACs were low; only 30

- day PBI lettuce, wheat forage and wheat hay samples had
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 any 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.

No additional rota tional crop data are required for the proposed uses on cereal grains, sugarcane,

and grass grown for seed.

860.1550 Proposed Tolerances

The Agency has determined that the residues of concern in both plant and livestock commodities

include residues of tr inexapac

- ethyl, determined as, trinexapac (CGA179500) . No p ermanent

tolerances have been established for the trinexapac residues

.

An adequate number of field trials at ~1x the proposed use rate are available for the RACs of

barley, wheat, sugarcane, and grass grown for seed. The Agency’s OECD Calculator was utilized for determining appropriate tolerance levels for RACs which showed quantifiable
residues in/on samples that were treated according to the proposed use patterns; s ee Appendix II

for tolerance calculations.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 48 of 70 Translation of residue data was made on appropriate situations. The available field trial data for

wheat may be translated to oats.

Residues of residues of CGA179500 concentrated in pearled barley (average processing factor of

1.2x), barley bran (average processing factor of 1.8x ), sugarcane molasses (average processing

factor of 5.8x), wheat bran (average processing factor of 1.8x) and wheat germ (average
processing factor of 1.1x). Residues also concentrated in wheat middling, with an average processing factor of 3.2x, based on three trials with processing factors of 0.34

- 0.55x and one trial
with a processing factor of 11.3x. Tolerances m ust be proposed for barley bran, sugarcane

molasses , wheat bran, and wheat middling . A detailed discussion of the assessment of processed
commodity tolerances is presented in the “860.1520 Processed Food/Feed” section of this

Summary Document.

A detailed discussion of the assessment of livestock commodity tolerances is presented in the

“860.1480 Mea t, Milk, Poultry, and Eggs” section of this Summary Document.

There are no established 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, a s well as Argentina, Brazil, Japan, Korea, and Australia have established or proposed

MRLs for trinexapac

- ethyl on cereal grains (0.02

- 0.5 mg/kg), cereal grain forages and fodders

(0.2

- 3 mg/kg), rapeseed (1

- 2 mg/kg), sugar cane (0.05

- 0.1 mg/kg), sugar fora ge and fodder (1
mg/kg), meat (0.02 kg/kg), edible offal (0.05 mg/kg), and/or milk (0.1

- 0.005 mg/kg).

A tolerance summary for trinexapac

- ethyl is presented in Table 22

. The petitioner should
submit a revised section F reflecting the recommended tolerances and commodity d efinitions

.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 49 of 70 Table 22

. Tolerance Summary for Trinexapac

- ethyl

. Commodity Proposed Tolerance
(ppm) Recommended Tolerance
(ppm) Comments

PP# 0F77 19

Grass, forage 1.6 1. 5

Grass, hay 3.5 4.0

Grass, seed screenings 45.0 4 0

Grass, straw 12.0 1 0

Cattle, fat 0.05 0.02

Cattle, meat 0.05 0.02

Cattle, meat byproducts 0.05 0.0 4 Based on highest residue in
cattle kidney

Goat, fat 0.05 0.02

Goat, meat 0.05 0.02

Goat, meat byproducts 0.05 0.0 4 Based on highest residue in
cattle kidney

Horse, fat 0.05 0.02

Horse, meat 0.05 0.02

Horse, meat byproducts 0.05 0.0 4 Based on highest residue in
cattle kidney

Sheep, fat 0.05 0.02

Sheep, meat 0.05 0.02

Sheep, meat byproducts 0.05 0.0 4 Based on highest residue in

cattle kidney

PP# 0F7720

Barley, grain 1.60 2.0

Barley, hay 0.70 0.8

Barley, straw 0.35 0.4

Cattle, kidney 0.05 Not needed Based on the recommended

tolerance for “cattle, meat
byproducts” an individual
tolerance for kidney is not

needed.

Sugarcane, cane 0.80 0.8

Hog, kidney 0.05 0.0 3 Hog, meat byproducts
Based on highest residue in
cattle kidney

Oat, forage 1.00 1.0 Data translated from wheat
forage

Oat, grain 4.10 4.0 Data translated from wheat
grain

Oat, hay 1.30 1.5 Data translated from wheat hay

Oat, straw 0.70 0.9 Data translated from wheat

straw

Wheat, forage 1.00 1.0

Wheat, grain 4.10 4.0

Wheat, hay 1.30 1.5

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 50 of 70 Table 22

. Tolerance Summary for Trinexapac

- ethyl

. Commodity Proposed Tolerance
(ppm) Recommended Tolerance
(ppm) Comments

Wheat, straw 0.70 0.9

Tolerances that need to be proposed

Barley bran None 2. 5

Sugarcane, molasses None 2. 5

Wheat bran None 6. 0

Wheat middlings None 10. 5

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 51 of 70

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 52 of 70 

## International Residue Limits

Trinexapac

- ethyl ( 112602; 07/05/2011 )

Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :

US Canada Mexico 2 

### Codex

40 CFR 180.XXX:

Plants: trinexapac

- ethyl, ethyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate and associated metabolite
trinexpac, 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid.

Livestock: trinexapac

- ethyl, ethyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate
and associated metabolite trinexpac, 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic

acid. None None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 53 of 70 Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :

US Canada Mexico 2 

### Codex

Barley, grain 2.0

Barley, hay 0.8

Barley, straw 0.4

Cattle, fat 0.02

Cattle, kidney Not needed

Cattle, meat 0.02

Cattle, meat byproducts 0.04

Goat, fat 0.02

Goat, meat 0.02

Goat, meat byproducts 0.04

Grass, forage 1.5

Grass, hay 4.0

Grass, seed screenings 40

Grass, straw 10

Hog, fat 0.02

Hog, meat 0.02

Hog, kidney 0.03

Horse, fat 0.02

Horse, meat 0.02

Horse, meat byproducts 0.04

Oat, forage 1.0

Oat, grain 4.0

Oat, hay 1.5

Oat, straw 0.9

Sheep, fat 0.02

Sheep, meat 0.02

Sheep, meat byproducts 0.04

Sugarcane, cane 0.8

Wheat, forage 1.0

Wheat, grain 4.0

Wheat, hay 1.5

Wheat, straw 0.9

Tolerances that need to be proposed

Barley, bran 2. 5

Sugarcane, molasses 2. 5

Wheat, bran 6. 0

Wheat, middlings 10. 5

Completed by: M. Negussie; 07/05/2011

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.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 54 of 70 References

DP# s : 328850, 328853, 328898
Subject: Trinexapac

- Ethyl. Petition for Registration of Use on Grasses Grown for Seed.

Summary of Analytical Chemistry and Residue Data . Petition Number 3F6571

From: D. Dotson

To: E. Wilson

Dated: Draft

MRID(s): 45898901

- 45898909, 46809305, 46809306

Attachments:

Appendix I

- Chemical Names and Structures of Metabolites
Appendix I I

- T olerance Assessment Calculations

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 55 of 70 Appendix I. Parent Compound and Identified Metabolites.

Table I. Chemical Names and Structures of Compounds Detected in the Grass, Rice, Wheat

, Goat , and

Hen Metabolism Studies.

Common name ; Company code Chemical name Chemical structure

Trinexapac

- ethyl ;

CGA

- 163935 ethyl 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylate

Trinexapac ;

CGA

- 179500 4

- (cyclopropylhydroxymethylene)

- 3,5

- dioxocyclohexanecarboxylic acid

CGA

- 275537 propane

- 1,2,3

- tricarboxylic acid

Metabolite A 4

- oxopentane

- 1,2,5

- tricarboylic acid

Terephthalic acid

(Metabolite C) NA

Aconitic acid

CGA

- 312753 (1E)

- prop

- 1

- ene

- 1,2,3

- tricarboxylic acid

CGA

- 313458 2

- (4

- cyclopropyl

- 4

- hydroxy

- 2

- oxobutyl)succinic acid

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 56 of 70 Table I. Chemical Names and Structures of Compounds Detected in the Grass, Rice, Wheat

, Goat , and

Hen Metabolism Studies.

Common name ; Company code Chemical name Chemical structure

Tricarballylic acid

CGA

- 275537 4

- [cyclopropyl(hydroxy)methyl]

- 3,5

- dihydroxybenzoic acid

Metabolite B 4

- (ethoxycarbonyl)

- 6

- oxocyclohex

- 2

- ene

1

- carboxylic acid

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 57 of 70 Appendix II. Tolerance Assessment Calculations.

The Organization for Economic Cooperation and Development (OECD) recently approved and
posted to the web the OECD MRL Calculator. The calculator was developed by an expert group
commissioned by the OECD Residue Chemistry Expert Group in 2008. As noted in the user’s

guide, the guiding principles in developing this tool were that it be a practical implementation of
sound statistical methods, that it be simple to use without requiring extensive statistical
knowledge from the user, that it provide clear MRL proposals for most data sets from residue

field trials, and that i t harmonize European Union and NAFTA procedures as much as possible.
The OECD calculator has been implemented for any new tolerance calculations begun in OPP on
or after April 1, 2011

The Microsoft Excel spreadsheets, user guide, and statistical white pap er are available from the
EPA website: (http://www.epa.gov/oppfead1/international/worksharing/oecd

- wkgroup.htm).

Barley

The dataset used to establish a tolerance for trinexapac

- ethyl as CGA179500 on barley consisted
of field trial data representing ap plication rates of 0.113

- 0.120 lb ai/A (1 application at 0.113

- 0.120 lb ai/A/application) with a 30

- day PHI for barley hay and 45

- day PHI for barley straw and
grain. The field trial application rates and PHIs are within 25% of the maximum label
applicatio n rate and minimum label PHI, respectively. The residue values that were entered into

the tolerance spreadsheet are provided in Table II

- 1.

Using the tolerance spreadsheet, the recommended tolerances are 2 ppm for barley grain, 0. 80

ppm for barley hay, and 0. 40 ppm for barley straw.

Table II

- 1. Residue data used to calculate tolerance for residues of

CGA179500 on barley.

Regulator: EPA EPA EPA

Chemical: Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl

Crop: Barley hay Barley straw Barley grain

PHI: 30 days 45 days 45 days

App. Rate: 0.113

- 0.119 lb ai/A 0.114

- 0.120 lb ai/A 0.114

- 0.120 lb ai/A

Submitter: Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection

MRID Citation: MRID 48043603 MRID 48043603 MRID 48043603

Residues of CGA179500

0.228 0.287 1.310

0.260 0.193 1.090

0.543 0.0822 0.900

0.407 0.202 1.000

0.367 0.0134 0.0698

0.460 0.0227 0.0870

0.134 0.0797 0.649

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 5 8 of 70 Table II

- 1. Residue data used to calculate tolerance for residues of

CGA179500 on barley.

Regulator: EPA EPA EPA

Chemical: Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl

Crop: Barley hay Barley straw Barley grain

PHI: 30 days 45 days 45 days

App. Rate: 0.113

- 0.119 lb ai/A 0.114

- 0.120 lb ai/A 0.114

- 0.120 lb ai/A

Submitter: Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection

MRID Citation: MRID 48043603 MRID 48043603 MRID 48043603

Residues of CGA179500

0.131 0.0653 0.858

0.0375 0.116 0.748

0.0505 0.118 0.900

0.0313 0.0545 0.533

0.0295 0.0763 0.523

0.104 0.0827 0.510

0.104 0.0900 0.533

0.134 0.112 0.562

0.158 0.0998 0.438

0.0100 0.0100 0.0451 (AVG)

0.0100 0.0100 0.0124 (AVG)

0.338 0.195 0.574

0.312 0.193 0.622

0.202 0.0905 0.718

0.158 0.0640 0.712

0.136 0.162 0.517

0.185 0.173 0.350

Table II

- 1a . Tolerance summary of trinexapac

- ethyl field trial data for barley hay.

Trinexapac ethyl

Barley Hay

Region / Country

GAP

Total number of data (n) 24

Percentage of censored data 0%

Number of non

- censored data 24

Lowest residue (LR) 0.010

Highest residue (HR) 0.543

Median residue (STMR) 0.147

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 59 of 70 Mean 0.189

Standard deviation (SD) 0.148

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 0.783

Rounded to the next MRL class 0.8

Table II

- 1b . Tolerance summary of trinexapac

- ethyl field trial data for barley straw

.

Trinexapac ethyl

Barley Straw

Region / Country

GAP

Total number of data (n) 24

Percentage of censored data 0%

Number of non

- censored data 24

Lowest residue (LR) 0.010
Highest residue (HR) 0.287

Median residue (STMR) 0.090

Mean 0.108

Standard deviation (SD) 0.071

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 0.392

Rounded to the next MRL class 0.4

Table II

- 1c . Tolerance summary of trinexapac

- ethyl field trial data for barley grain

.

Trinexapac ethyl

Barley Grain

GAP

Total number of data (n) 24

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 60 of 70 Percentage of censored data 0%

Number of non

- censored data 24

Lowest residue (LR) 0.012

Highest residue (HR) 1.310

Median residue (STMR) 0.568

Mean 0.594

Standard deviation (SD) 0.331

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 1.918

Rounded to the next MRL class 2



### Wheat

The dataset used to establish a tolerance for trinexapac

- ethyl as CGA179500 on wheat consisted

of field trial data representing application rates of 0.113

- 0.120 lb ai/A (1 application at 0.113

- 0.120 lb ai/A/application) with a 30

- day PHI for wheat forage and hay and a 45

- day PHI for

wheat straw and grain. The field trial application rates and PHIs are within 25% of th e maximum label application rate and minimum label PHI, respectively. The residue values that
were entered into the tolerance spreadsheet are provided in Table II

- 2.

Using the tolerance spreadsheet, th e recommended tolerances are 1.0 ppm for wheat forage

, 1.5
ppm for wheat hay, 0.9 ppm for wheat straw, and 4.0 ppm for wheat grain.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 61 of 70 Table II

- 2. Residue data used to calculate tolerance for residues of CGA179500 on wheat.

Regulator: EPA EPA EPA EPA

Chemical: Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl

Crop: Wheat forage Wheat hay Wheat straw Wheat grain

PHI: 30 days 30 days 45 days 45 days

App. Rate: 0.114

- 0.120 lb ai/A 0.114

- 0.120 lb ai/A 0.113

- 0.120 lb ai/A 0.113

- 0.120 lb ai/A

Submitter: Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection

MRID Citation: MRID 48043601 MRID 48043601 MRID 48043601 MRID 48043601

Residues of CGA179500

0.0527 0.165 0.0773 0.317

0.0660 0.165 0.0600 0.324

0.175 0.540 0.305 4.030

0.268 0.453 0.0807 2.610

0.357 0.547 0.217 1.030

0.295 0.615 0.238 0.975

0.0560 0.109 0.0562 0.470

0.0595 0.103 0.0572 0.473

0.0682 0.0818 0.0765 0.809

0.0638 0.139 0.0957 0.732

0.108 0.173 0.0272 0.298

0.0798 0.198 0.0185 0.242

0.228 0.310 0.188 0.900

0.198 0.295 0.149 1.080

0.0895 0.0197 0.0100 0.0707

0.105 0.0303 0.0149 0.0712

0.0250 0.0358 0.0995 0.313

0.0220 0.0325 0.107 0.308

0.0405 0.0855 0.473 0.761

0.0445 0.0698 0.437 0.867

0.0136 0.0472 0.138 0.477

0.0187 0.0607 0.155 0.570

0.900 1.260 0.637 1.640

0.975 1.090 0.560 1.640

0.0100 0.143 0.552 0.996 (AVG)

0.0660 0.0100 0.618 0.554 (AVG)

0.173 0.312 0.162 0.0972

0.157 0.277 0.134 0.0993

0.200 0.410 0.0435 0.144

0.144 0.833 0.0390 0.148

0.403 0.720 0.380 1.100

0.360 0.146 0.175 1.180

0.0104 0.0730 0.0978 0.410

0.0100 0.193 0.0653 0.387

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 62 of 70 Table II

- 2. Residue data used to calculate tolerance for residues of CGA179500 on wheat.

Regulator: EPA EPA EPA EPA

Chemical: Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl

Crop: Wheat forage Wheat hay Wheat straw Wheat grain

PHI: 30 days 30 days 45 days 45 days

App. Rate: 0.114

- 0.120 lb ai/A 0.114

- 0.120 lb ai/A 0.113

- 0.120 lb ai/A 0.113

- 0.120 lb ai/A

Submitter: Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection

MRID Citation: MRID 48043601 MRID 48043601 MRID 48043601 MRID 48043601

Residues of CGA179500

0.0100 0.218 0.0810 0.333

0.0258 0.0312 0.0952 0.303

0.0383 0.0397 0.0310 0.437

0.112 0.240 0.0352 0.453

0.0757 0.240 0.393 0.867

0.0902 0.263 0.815

Table II

- 2a . Tolerance summary of trinexapac

- ethyl field trial data for wheat forage.

Trinexapac ethyl

Wheat Forage

Region / Country

GAP

Total number of data (n) 40

Percentage of censored data 0%

Number of non

- censored data 40

Lowest residue (LR) 0.003

Highest residue (HR) 0.975

Median residue (STMR) 0.078

Mean 0.154

Standard deviation (SD) 0.210

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 0.995

Rounded to the next MRL class 1

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 63 of 70 Table II

- 2b . Tolerance summary of trinexapac

- ethyl field trial data for wheat hay.

Trinexapac ethyl

Wheat Hay

Region / Country

GAP

Total number of data (n) 39

Percentage of censored data 0%

Number of non

- censored data 39

Lowest residue (LR) 0.010

Highest residue (HR) 1.260

Median residue (STMR) 0.165

Mean 0.270

Standard deviation (SD) 0.295

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 1.448

Rounded to the next MRL class 1.5

Table II

- 2c . Tolerance summary of trinexapac

- ethyl field trial data for wheat straw.

Trinexapac ethyl

Wheat Straw

Region / Country

GAP

Total number of data (n) 40

Percentage of censored data 0%

Number of non

- censored data 40

Lowest residue (LR) 0.010
Highest residue (HR) 0.637

Median residue (STMR) 0.103

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 64 of 70 Mean 0.186

Standard deviation (SD) 0.180

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 0.908

Rounded to the next MRL class 0.9

Table II

- 2d . Tolerance summary of trinexapac

- ethyl field trial data for wheat grain.

Trinexapac ethyl

Wheat Grain

Region / Country

GAP

Total number of data (n) 39

Percentage of censored data 0%

Number of non

- censored data 39

Lowest residue (LR) 0.071

Highest residue (HR) 4.030

Median residue (STMR) 0.473

Mean 0.710

Standard deviation (SD) 0.733

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 4.030

Rounded to the next MRL class 4

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 65 of 70 Sugarcane

The dataset used to establish a tolerance for trinexapac

- ethyl as CGA179500 on sugarcane

consisted of field trial data representing application rates of 0.313

- 0.341 lb ai/A (1 application at

0.313

- 0.341 lb ai/A/application) with a 28

- day PHI. The field trial application rates and PHIs are

within 25% of the maximum label application rate and minimum label PHI, respectively . The
residue values that were entered into the tolerance spreadsheet are provided in Table II

- 3. Using
the tolerance spreadsheet, the recommended tolerance is 0.8 ppm for sugarcane.

Table II

- 3

. Residue data used to calculate tolerance for residues of

CGA179500 on sugarcane.

Regulator: EPA

Chemical: Trinexapac

- ethyl

Crop: Sugarcane

PHI: 28 days

App. Rate: 0.313

- 0.341 lb ai/A

Submitter: Syngenta Crop Protection

MRID Citation: MRID 48043602

Residues of CGA179500

0.0100

0.0100

0.0388

0.0385

0.0623

0.0530

0.240

0.198

0.270

0.327

0.400

0.426

0.0473

0.100

0.125

0.205

Table II

- 3a . Tolerance summary of trinexapac

- ethyl field trial data for sugarcane.

Trinexapac

- ethyl

Sugarcane

Region / Country

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 66 of 70

GAP

Total number of data (n) 16

Percentage of censored data 0%

Number of non

- censored data 16

Lowest residue (LR) 0.010
Highest residue (HR) 0.426

Median residue (STMR) 0.113

Mean 0.159

Standard deviation (SD) 0.139

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 0.717

Rounded to the next MRL class 0.8



### Grass

The dataset used to establish a tolerance for trinexapac

- ethyl as CGA179500 on grass consisted

of field trial data representing application rates of 0.505

- 0.537 lb ai/A (1 application at 0.505

- 0.537 lb ai/A/application) with a 35

- day PHI for grass straw and seed screenings and a 49

- day
PHI for grass forage and hay. The field trial application rates and PHIs are w ithin 25% of the

maximum label application rate and minimum label PHI, respectively. The residue values that
were entered into the tolerance spreadsheet are provided in Table II

- 4.

Using the tolerance spreadsheet, the recommended tolera nces are 1.5 ppm f or grass f orage, 4.0
ppm for grass hay, 10 ppm for grass straw, and 4 0 ppm for grass seed screenings.

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 67 of 70 Table II

- 4

. Residue data used to calculate tolerance for residues of CGA179500 on grass.

Regulator: EPA EPA EPA EPA

Chemical: Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl Trinexapac

- ethyl

Crop: Grass forage Grass hay Grass straw Grass seed
screenings

PHI: 49 days 49 days 35 days 35 days

App. Rate: 0.505

- 0.537 lb ai/A 0.505

- 0.537 lb ai/A 0.505

- 0.537 lb ai/A 0.505

- 0.537 lb ai/A

Submitter: Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection Syngenta Crop

Protection

MRID Citation: MRID 48043701 MRID 48043701 MRID 48043701 MRID 48043701

Residues of CGA179500

0.0753 0.180 0.427 1.090

0.0843 0.228 0.260 0.317

0.0308 0.116 0.330 1.020

0.0480 0.101 0.282 1.090

0.0543 0.347 0.215 0.463

0.0405 0.100 0.767 0.325

0.0793 0.397 5.510 20.000

0.0975 0.292 5.220 16.600

0.235 0.875 3.470 10.300

0.260 1.020 2.820 11.000

0.116 0.523 1.370 4.860

0.0798 0.413 1.200 5.590

0.0815 0.142 0.190 0.447

0.0388 0.247 0.325 0.471

0.0533 0.315 0.732 4.330

0.0320 0.218 1.180 4.400

0.372 1.720 3.830 17.300

0.309 3.400 5.670 13.500

0.767 1.800 3.930 15.400

1.000 1.080 4.770 12.000

0.156 0.404 1.320 0.883

0.145 0.340 1.440 0.883

1.200 1.640

0.520 2.130

Table II

- 4a . Tolerance summary of trinexapac

- ethyl field trial data for grass forage.

Trinexapac ethyl

Grass Forage

Region / Country

GAP

Total number of data (n) 24

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 68 of 70 Percentage of censored data 0%

Number of non

- censored data 24

Lowest residue (LR) 0.031

Highest residue (HR) 1.200

Median residue (STMR) 0.091

Mean 0.245

Standard deviation (SD) 0.318

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 1.518

Rounded to the next MRL class 1.5

Table II

- 4b . Tolerance summary of trinexapac

- ethyl field trial data for grass hay.

Trinexapac ethyl

Grass Hay

Region / Country

GAP

Total number of data (n) 22

Percentage of censored data 0%

Number of non

- censored data 22

Lowest residue 0.100

Highest residue 3.400

Median residue 0.344

Mean 0.648

Standard deviation (SD) 0.784

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 3.400

- Mean + 4 SD 3.786

- CF x 3 Mean 1.944

Unrounded MRL 3.786

Rounded MRL 4

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 69 of 70 Table II

- 4c . Tolerance summary of trinexapac

- ethyl field trial data for grass straw.

Trinexapac ethyl

Grass Straw

Region / Country

GAP

Total number of data (n) 24

Percentage of censored data 0%

Number of non

- censored data 24

Lowest residue (LR) 0.190

Highest residue (HR) 5.670

Median residue (STMR) 1.345

Mean 2.043

Standard deviation (SD) 1.865

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 9.501

Rounded to the next MRL class 10

Table II

- 4d . Tolerance summary of trinexapac

- ethyl field trial data for grass screening.

Trinexapac ethyl

Grass Seed Screening

Region / Country

GAP

Total number of data (n) 22

Percentage of censored data 0%

Number of non

- censored data 22

Lowest residue (LR) 0.317
Highest residue (HR) 20.000

Median residue (STMR) 4.365

### Trinexapac

- ethyl Summary of Analytical Chemistry and Residue Data DP# 37 7921



### Page 70 of 70 Mean 6.467

Standard deviation (SD) 6.705

Correction factor for censoring (CF) 1.000

Proposed MRL estimate

Unrounded 33.287

Rounded to the next MRL class 40