Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

MEMORANDUM

Date: September 30, 2011

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 Chemistry and Residue Data.

PC Code: 112602 DP Barcodes: 377921 

Decision No.: 432768 and 433096 Registration Nos.: 100-727, 100-949 and 100-

1241

Petition Nos.: 0F7719 and 0F7720 Regulatory Action: Section 3 First Food Use 

Registrations

Risk Assessment Type: NA Case No.: NA

TXR No.: NA CAS No.: 95266-40-3

MRID No.: 48043701-09, 47101606, 

47101603, 48043601-04, 45898901-09, 

46809305-06

40 CFR: NA

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#377921

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MRID Summary Table

MRID No. Study Type Comments

48043704 860.1300 (hen metabolism study) New DER; 48043704.der (860.1300)

48043705 860.1300 (goat metabolism study) New DER; 48043705.der (860.1300)

48043702 860.1340 (crop analytical method) New DER; 48043702.der, including 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; 47101601.der (860.1380)

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

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

48043603 860.1500 (barley field trials)

860.1520 (barley processing study)

New DER; 48043603.der1 (860.1500)

New DER; 48043603.der2 (860.1520)

48043601 860.1500 (wheat field trials)

860.1520 (wheat processing study)

New DER; 48043601.der1(860.1500)

New DER; 48043601.der2(860.1520)

48043602 860.1500 (sugarcane field trials)

860.1520 (sugarcane processing study)

New DER; 48043602.der1(860.1500)

New DER; 48043602.der2(860.1520)

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

48043709 860.1850 (confined rotational crop study) New DER; 48043709.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 860.1850 (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 petitions, 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#377921

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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 grown for seed 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 seasonal rate of 0.5 lb ai/A, a 35-day preharvest interval (PHI) for mature grass, and a 

49-day pre-grazing interval (PGI) 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 on 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 45-day PHI for cereal grains and a maximum seasonal rate of 0.31 lb ai/A

and a 28-day PHI for sugarcane.

Prior to receipt of these new petitions, no tolerances had 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. Under 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 CGA179500, 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
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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-dioxocyclohexanecarboxylic 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 .................................................................0.70 ppm

Barley, straw ..............................................................0.35 ppm

Cattle, kidney .............................................................0.05 ppm

Sugarcane, cane .........................................................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 ...............................................................4.10 ppm

Wheat, hay..................................................................1.30 ppm

Wheat, straw...............................................................0.70 ppm

The nature of trinexapac-ethyl residues in grass, cereal grain and sugarcane commodities and 

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

The residues of concern in plants and livestock for 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, 7/12/11).

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-quadrupole 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 

radiovalidation 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#377921

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trinexapac acid (CGA179500) in livestock matrices. The requirements for radiovalidation data 

are fulfilled and an adequate ILV study has been submitted. 

In the field 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 LCMS/MS method (REM 137.14). The methods were adequately validated both prior to and in 

conjunction with the analysis of the field trial, processing, and feeding study samples. The 

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 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.

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

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

for wheat grain, 12 months 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 samples in the current submissions. In addition, the petitioner 

submitted the results of a storage stability study with CGA-163935 (trinexapac-ethyl) and CGA179500 (trinexapac) in grass (clippings and thatch + sod). 

Since actual storage durations of the 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 stability data 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 submitted data, HED has concluded that tolerances for residues of trinexapac-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#377921

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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.

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, 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/kg), rapeseed (1-2 mg/kg), sugarcane (0.05-0.1 mg/kg), sugar forage and fodder (1 

mg/kg), meat (0.02 mg/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. Provided 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 tolerances.

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 expression 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 specified below is to be determined by measuring both trinexapac-ethyl, ethyl 4-

(cyclopropylhydroxymethylene)-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....................................40 ppm

Grass, straw...............................................10 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
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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 ....................................................................0.02 ppm

Cattle, meat ................................................................0.02 ppm

Cattle, meat byproducts.............................................0.04 ppm

Goat, fat......................................................................0.02 ppm

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

Goat, meat byproducts...............................................0.04 ppm

Horse, fat ....................................................................0.02 ppm

Horse, meat ................................................................0.02 ppm

Horse, meat byproducts.............................................0.04 ppm

Sheep, fat....................................................................0.02 ppm

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

Sheep, meat byproducts.............................................0.04 ppm

Hog, fat.......................................................................0.02 ppm

Hog, meat ...................................................................0.02 ppm

Hog meat byproducts.................................................0.03 ppm

860.1380 Storage Stability

Since actual storage durations of the 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.

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 grains throughout the U.S. Trinexapacethyl 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 formulations of trinexapac-ethyl are currently registered for use on perennial ryegrass 
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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 presented below in 

Tables 1 and 2.

Table 1.Trinexapac-ethyl Nomenclature.

Compound

Common name Trinexapac-ethyl

Company experimental name CGA163935

IUPAC name ethyl (RS)-4-cyclopropyl(hydroxy)methylene-3,5-dioxocyclohexanecarboxylate

CAS name ethyl 4-(cyclopropylhydroxymethylene)-3,5-dioxocyclohexanecarboxylate

CAS registry number 95266-40-3

End-use product (EP) 1.0 lb/gal EC (PalisadeTM EC; EPA Reg. No. 100-949)

2.0 lb/gal EC (Palisade 2EC; EPA Reg. No. 100-1241)

Regulated Metabolite

Common Name Trinexapac

Company Experimental 

Name

CGA-179500

IUPAC name (RS)-4-cyclopropyl(hydroxy)methylene-3,5-dioxocyclohexanecarboxylic acid

CAS name 4-(cyclopropylhydroxymethylene)-3,5-dioxocyclohexanecarboxylic acid

CAS registry number 104273-73-6

OH

O

O

O

O

H3C

O

O

O

HO OH
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Table 2.Physicochemical Properties of Trinexapac-ethyl.

Parameter Value Reference

Melting point/range 36.1-36.6°C Provided in MRID 

pH 3.3 46809305

Density (20oC) 1.215 g/cm3

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, pKa 4.57

Octanol/water partition coefficient, 

Log(KOW) 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 formulations 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, PalisadeTM EC; EPA 

Reg. No. 100-949) and the 2 lb/gal EC (25.5%, Palisade® 2EC; EPA Reg. No. 100-1241). Both 

EC formulations are currently registered for use on perennial ryegrass in the Pacific Northwest. 

The petitioner did not provide specimen labels for the two end-use products; the proposed use 

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

Table 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 seed1

Broadcast foliar 

application

1.0 lb/gal 

EC

[100-949]

2.0 lb/gal 

EC

[100-1241]

0.09-

0.50 1

0.5 7-10 235

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 allow 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
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Table 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

NA3

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 

strongly erect). Apply in a 

minimum of 20 gal/A.

Broadcast foliar 

application 0.05 2 NS3

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 (1st 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

NA328

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 have 

appeared. 
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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 References: 45898902.der (grass); 45898904.der (spring wheat); 46809306.der (rice)

Grass. In the grass metabolism study, [1,2,6-

14C-cyclohexyl]trinexapac-ethyl (98.1% 

radiochemical purity) was applied to field plots of tall fescue grass approximately 45 days prior 

to normal maturity, as a single broadcast foliar application at 0.5 lb ai/A (560 g ai/ha; 1x rate). 

[

14C]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 straw, 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 similar in each 

grass matrix. Parent was not detected in any matrix, and the major 14C-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), Metabolite 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-

14C] 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 30.321 21.79 31.041 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#377921

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

Single Foliar Application of [1,2,6-

14C] 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 50.848 16.29 51.161 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 extracted 586.38 1.752 88.76 4.240 89.96 4.906 93.30 6.655 55.54 0.030

Unextracted 69.38 0.190 9.83 0.700 9.21 0.501 5.08 0.360 34.83 0.019

Accountability 795.8 98.6 99.2 98.4 90.4

1 Total residues of CGA-179500 and CGA-275537 in forage and straw include 14C-residues of these compounds released by 

enzymatic hydrolysis.

2 Expressed in [14C] 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 extracted + Total unextracted)/(TRR from combustion analysis; see TABLE C.2.1) * 100.

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

14C-cyclohexyl]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 14Ctest 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 <0.001 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 stored 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 14C-Residues in Rice Matrices Following a Single 

Application of [14C] 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#377921

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Table 5. Characterization and Identification of 14C-Residues in Rice Matrices Following a Single 

Application of [14C] 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 37.6 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) 41.4 0.008 8.1 0.011 15.7 0.010

Accountability 599.8 100.4 103.3

Compound/Fraction

Straw (82 DAT) Husks (82 DAT) Grain (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 124.9 0.040 34.5 0.058 0.7 <0.001

Minor Unknowns 22.4 0.004 6.7 0.011 1.7 0.001

Unresolved 323.2 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) 440.5 0.065 41.1 0.069 72.0 0.061

Accountability 5107.4 104.4 100.7

1

Polar 14C-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 unextracted).

Table 6. Summary of Characterization and Identification of 14C-Residues in Mature Rice Matrices 

Following a Single Application of [14C] 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 213.9 0.220 17.0 0.378 3.2 0.034

CGA-313458 27.2 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 29.1 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 14C-residues (TLC origin) 330.6 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 412.6 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) 50.7 0.011 16.0 0.356 0 <0.001
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Table 6. Summary of Characterization and Identification of 14C-Residues in Mature Rice Matrices 

Following a Single Application of [14C] 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 699.6 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 fraction, 

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 CGA275537 accounted for 26-31% for their total levels in straw, 53-60% in husks, and 35-68% in grain.

3

Polar 14C-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 unextracted).

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

14C-cyclohexyl]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 

[

14C] trinexapac-ethyl in order to generate additional amounts of selected metabolites for detailed 

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 identifications 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, substantial portions 

of the radioactivity either remained at TLC origins or were 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 independently confirmed because of the lack of 

supporting raw data.

The submitted wheat metabolism study is inadequate. 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) forage 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 husks were not reported

Table 7. Characterization and Identification of 14C-Residues in Mature Wheat Matrices Following 

a Single Foliar Application of [

14C]Trinexapac-ethyl at 0.13 lb ai/A.1

Fraction/Metabolite 2 % Total Radioactive Residues

Grain Husks Straw

CGA-275537 (II2) 3.1 NA 2.4
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Table 7. Characterization and Identification of 14C-Residues in Mature Wheat Matrices Following 

a Single Foliar Application of [

14C]Trinexapac-ethyl at 0.13 lb ai/A.1

Fraction/Metabolite 2 % Total Radioactive Residues

Grain Husks Straw

CGA-329773 (II3) 10.9 NA 3.1

CGA-312753 (I2a) ND 4.3 1.8

Trinexapac (I5) 27.9 16.7 12.8

Total Identified 41.9 21.0 20.1

TLC Unknowns (I1, I4, II4) 2.4 6.7 2.9

TLC origin (II1) 36.8 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) 415.1 11.4 11.2

Accountability 595.4 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 14C-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 extracted + Total unextracted).

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

isolated: II2, II3, trinexapac, and II4. 

ND = not detected; NA = fraction not analyzed.

HED Conclusions

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

14Ccyclohexyl]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 14C-trinexapac-ethyl rapidly undergoes hydrolysis of the ethyl ester to form 

trinexapac. Also, the tricarboxylic acid metabolite, CGA 275537 was identified at the 4x rate in 

rice (3-17%TRR) at 60 DAT and in grass (9-15% TRR). This metabolite has the potential for 

inhibiting the citric acid cycle. However, given the levels of 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 of 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 References: 48043705.der & 45898905 (goat metabolism) and 48043704.der (poultry metabolism)

Goat
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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-

14C-cyclohexyl] trinexapac-ethyl (97.9% 

radiochemical purity) at a dose of 150 mg ai/goat/day, which was equivalent to 2.92-3.21 mg 

ai/kg body weight/day. 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 omental), 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 radioactivity 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 rapid 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 1/3rd to 1/8th as high as they were in the subsequent 

a.m. samples. 14C-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 14C-Residues in Tissues and Milk from Goats Dosed 

for 4 Days with [14C] 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 18.0 0.064 4.5 0.266 4.0 0.011 ND -- 9.0 0.007

Accountability 2102.5 99.5 107.6 98.1 100.0

1 Unidentified polar residues associated with the column void volume.

2 Residues remaining in solids after solvent extractions.

3 Accountability = (Total extractable + Total unextracted)/(TRR from combustion analysis; see TABLE C.2.1)*100.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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-

14C-cyclohexanedione]trinexapac-ethyl (97.7% radiochemical 

purity) at a dose of 150 mg ai/day. The actual mean dosing rate from day 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 hindquarter), 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 the 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) accounted 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 

amount 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 14Ctrinexapac-ethyl (cyclohexadione ring label) in laying hens; the specific activity was 40.9 

μCi/mg. The test substance was administered orally via gelatin capsule to five 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. Excreta were collected once daily and cage wash 

was collected after sacrifice. The hens were euthanized approximately 22 hours after 

administration of the final dose. After sacrifice, the peritoneal fat, subcutaneous fat with skin 

attached, liver, kidney, muscle (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#377921

Page 18 of 70

prior to analysis. The composite egg white sample was extracted, fractionated and 

chromatographically 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 were 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 (88-91%) 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 which 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. For 

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 14C-residue in milk and 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 was not detected in muscle or milk. 

However, the CGA 113745 metabolite had no structural alerts and has a carboxyl group that 

should make it readily excreted, making it also of less toxicological concern. 

The nature of the residue in livestock is adequately understood based on the available ruminant

and poultry metabolism studies. Based on the available data, the residues of concern in livestock 

commodities for tolerance enforcement and risk assessment purposes are free and conjugated 

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

860.1340 Residue Analytical Methods
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

Page 19 of 70

Plant method

DER References: 48043702.der (Includes MRID 48043703)

In conjunction with the previous grass petition (PP#3F6571; DP#s 328850, 328853, 328898), 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 concluded 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 conjugated 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 triplequadrupole 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 studies 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 for 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 extracting 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 14C-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 deviations 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 ranging 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#377921

Page 20 of 70

The submitted LC/MS/MS method, Method GRM020.01A, is adequate for data collection and

tolerance enforcement. The method showed that the parent (trinexapac-ethyl) rapidly 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 validated in an independent laboratory. 

Livestock Method

DER References: 48043706.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 LCMS/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 [14C]trinexapac acid from goat liver and 

chicken egg white samples. The extraction efficiencies were determined 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 102% and 105% in the 14C-labeled goat liver and 

chicken egg white samples, respectively. 

Method REM 137.14, subsamples of 14C-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 14Clabeled goat liver samples and were <0.01 ppm for the 14C-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.

Method 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 matrix tested.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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 14C-labeled goat liver and chicken egg white 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 DG1 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 adequate 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 References: 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. Residues of trinexapac were determined using a HPLC/UV twocolumn 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 extract aliquot is transferred to a solid phase extraction cartridge. 
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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 

validated (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 CGA179500 (trinexapac) in grass (clippings and thatch + sod) was also submitted. Untreated samples 

of each of these commodities were homogenized and fortified with either CGA-163935 or CGA179500 at a level of 2 ppm. Samples were placed in frozen storage at approximately -20 oC and 

analyzed 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 CIBAGEIGY Method 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 method CIBA-GEIGY Method 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 Method 052190 titled “Analytical Method for 

the Determination of CGA-163935 and CGA-179500 in Soil” was used to determine residues of 

CGA-163935 and CGA-179500 in NY thatch + sod samples due to unacceptable performances 

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 soil. The LOQ was not reported 

for any method. 

Residues of CGA-163935 and CGA-179500 appear to be stable in/on Bermuda grass and 

bluegrass clippings for up to 6 months. Residues of CGA-163935 and CGA-179500 appear to be 

relatively steady in/on Bermuda grass 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 in 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. Samples were stored frozen (≤ -18oC) and then analyzed with 

freshly fortified samples; actual dates of analysis were not provided. The petitioner stated 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#377921

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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 of samples from the crop field trials, processing, and 

livestock feeding studies submitted to support these petitions are presented in Table 9. 

Table 9. Summary of Storage Conditions and Durations of 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 commodities12-24 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 days1 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 days1

Fat CGA179500 152 days1

Blood CGA179500 152 days1

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

Barley straw CGA179500 12-24 months for wheat (grain and straw) -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

Wheat hay 12-24 months for wheat (grain and straw) 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#377921

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Table 9. Summary of Storage Conditions and Durations of 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 monthsfor wheat (grain and straw) 

Sugarcane (RAC) CGA179500 -10 457-658 days

Molasses CGA179500 -10 439-535 days No data available for sugarcane processed 

Refined Sugar commodities

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 the 

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 oilseeds 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 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 stability data support the storage 

conditions and durations of CGA179500 for the poultry livestock feeding 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#377921

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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 10 using recent Agency guidance on calculating dietary exposure from 

“reasonably balanced” livestock diets (ChemSAC draft memo, 6/2008). Also, ChemSAC has 

considered revising the current guidance regarding the use of tolerance–level residues when 

estimating livestock dietary burdens. The use of the highest residue rather than the tolerance

would bring EPA into harmonization with our NAFTA partners, with other countries, and with 

OECD 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#377921

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Table 10. Maximum Reasonable Dietary Burdens (MRDB) of Trinexapac-Ethyl Residues Fed to Livestock.

Feedstuff Type1 % Dry 

Matter2 % Diet2 Highest Residue(ppm) 3

Dietary Contribution 

(ppm)4

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

Wheat, hay R 88 15 1.3 0.22

Barley, grain CC 88 50 1.3 0.74

Wheat, milled byproducts5 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 0.12

Wheat, hay R 88 20 1.3 0.30

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 cattle; contribution = (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 forage regrowth has not been considered a feedstuff in the proposed cattle 

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

1) Most of the areas growing grass for seed are not near feedlots 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 

operations, or fed to local growing cattle and not to Table 1 production reference 
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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animals."

Livestock feeding studies

DER References: 47101603.der.doc (dairy cattle feeding study), 48043604.der.doc (poultry 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 (1x), 5.59 (2.8x) ppm and 19.9 (10x) ppm in their diet (dryweight 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 

analyzed. Livestock commodities were sacrificed ~20-23 hours after the final dose on Study 

Days 29 and 30. Samples of liver, kidney, fat (perirenal and omental), muscle (round, loin and 

diaphragm) and blood 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 0.01 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 conducted using control samples of each matrix fortified with CGA 179500 at 0.05-

0.20 ppm. According to the study report, these samples were stored frozen (≤ -18oC) 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 

residues 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#377921

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A summary of residue data from the ruminant feeding study with trinexapac-ethyl is presented in 

Table 11.

Table 11. Summary of Residue Data from Dairy Cattle Feeding Study with CGA 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#377921

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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 observed 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 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 residues are presented in Table13.

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 <0.005 2.03 0.002

Liver <0.02 2.03 0.01

Kidney 0.05 2.03 0.02

Muscle (loin) <0.02 2.03 0.01

Muscle (round) <0.02 2.03 0.01

Fat (perirenal) <0.02 2.03 0.01

Fat (omental) <0.02 2.03 0.01

1

 Calculated from the maximum residues observed at the dose level closest to the reasonable dietary burdens (RDB)

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 0.004 Not required

Liver 1.8 0.02 0.02

Kidney 1.8 0.04 0.04

Muscle 1.8 0.018 0.02

Fat 1.8 0.018 0.02

Swine

Liver 1.4 0.014 0.02

Kidney 1.4 0.028 0.03

Muscle 1.4 0.014 0.02

Fat 1.4 0.014 0.02

1

 Calculated from dietary burden x transfer coefficient from Table 12.

HED Conclusions

Pending submission of information of sample storage conditions and durations, the 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 appropriate for the free 

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

commodities: 0.02 ppm for the fat and meat of cattle, goat, horse, and sheep; 0.04 ppm for the 

meat byproduct of cattle, goat, horse, and sheep; and 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#377921

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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 (1.2x), 9.9 ppm (3.3x), and 33 ppm (12.3x) 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 commodities 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 stored 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 CGA179500 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 samples 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 also below the LOQ (<0.01 ppm) in fat and liver samples from 

the 3x dose group, but were above 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 lowdose (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 

Table 14.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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.

Egg19.9 (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 each 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 

coefficient 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 residues are presented in Table 16.

Table 15. Residue-Level-to-Feed Ratios (Transfer Coefficients) in Poultry Egg and 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 0.0216

Muscle <0.01 37 0.0003

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

Table 16. 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 0.065 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#377921

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The trinexapac-ethyl as CGA179500 residue data from the poultry feeding study is adequate to 

satisfy data requirements. Based on the transfer coefficients for hen tissues 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 References: 48043603.der1 (barley), 48043601.der1 (wheat), 48043602.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 results from 

these field trials discussed below and the residue data are summarized in Table 17.

Table 17. 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 = 0.11 lb ai/A total application rate, 45-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 3930.07 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 (trinexapac-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). 

Each field trial included one treated plot 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#377921

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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/MS). 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, acceptable storage stability data are 

available for wheat (grain and straw) and rapeseed pending submission of a copy of the 

analytical 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, 

CGA179500 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 at longer posttreatment 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 increased 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 

field 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 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) following 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#377921

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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 trials), 6 (OK; 1 trial), 7 (ND, SD, NE; 5 trials), 8 (TX, 

OK; 6 trials), and 11 (ID; 1 trial). Each field trial included one treated plot in which trinexapacethyl 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 residues 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 samples 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). The available storage 

stability data 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 posttreatment 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: 

The 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 field 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 supported by adequate storage 

stability data.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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). Each field trial included one treated plot in which trinexapac-ethyl 

was applied to sugarcane as a single 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 for 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 samples, 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 storage 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). The available 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 of 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 residue 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 data 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#377921

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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 of field trial 

samples. The LOQ is 0.05 ppm for trinexapac in each grass 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 concentrate (EC) formulation containing 2.1 lb ai/gal (trinexapacethyl 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). Each 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 with 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. The 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 data are available for 

wheat (grain and straw) and rapeseed pending submission of a copy of the analytical 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#377921

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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 the 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 includes 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 40 ppm for residues of CGA179500 

in/on grass forage, hay, straw, and seed screenings, respectively. 

860.1520 Processed Food and Feed

DER References: 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 modified 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 grain 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. No storage stability 

data are available 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. The available 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#377921

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A summary of residue data from the barley processing study is presented in Table 18. 

CGA179500 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 bran. 

CGA179500 residues in/on barley RAC samples collected for 5x processing 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 the 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 both application rates in the ND trial.

Table 18. Residue Data from Barley Processing Studies with Trinexapac-ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) 

PHI 

(days)

Residues 

(ppm)

Processing 

Factor1

Northwood, ND; 2008 (C13ND081704) 1x

Barley Grain (RAC) 0.115 45 0.503

0.550

0.477

--

Pearled barley 0.115 45 0.778

0.7182

1.5x

Flour 0.115 45 0.260

0.3122

0.6x

Bran 0.115 45 0.950

1.122

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

0.8922

1.1x

Flour 0.115 45 0.235

0.1822

0.3x

Bran 0.115 45 1.38

1.262

1.8x
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Table 18. Residue Data from Barley Processing Studies with Trinexapac-ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) 

PHI 

(days)

Residues 

(ppm)

Processing 

Factor1

Northwood, ND; 2008 (C13ND081704) 5x

Barley Grain (RAC) 0.578 45 9.13

5.20

5.86

--

Pearled barley 0.578 45 10.1

8.582

1.4x

Flour 0.578 45 4.60

3.702

0.6x

Bran 0.578 45 10.8

10.92

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

4.132

0.9x

Flour 0.575 45 1.40

1.402

0.3x

Bran 0.575 45 10.1

9.582

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

Processing 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 1.8x 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 procedures. Adequate descriptions were provided of the processing procedures, 

including material balance summaries.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Residues of trinexapac-ethyl as CGA179500 were determined using modified 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 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. No storage stability 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 

(refer to 45898903.der, previously reviewed). The 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 months. 

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 sugar.

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#377921

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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 

Factor1

Clewiston, FL; 2007 (E19FL078492) 1x

Sugarcane Sugarcane (RAC) 0.341 28 0.0385

0.0752

0.0475

--

Molasses 0.341 28 0.323

0.3222

6.0x

Refined Sugar 0.341 28 <LOQ

<LOQ2

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

1.282

6.7x

Refined Sugar 0.322 28 0.0238

0.03002

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

1.772

6.2x

Refined Sugar 1.66 28 <LOQ

<LOQ2

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

9.232

4.4x

Refined Sugar 1.59 28 0.220

0.2432

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

Processing 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; average 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 concentration 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#377921

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Wheat

Syngenta 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 procedures. 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 harvest/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. The available 

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

for up to 742 days (refer to 45898903.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. Average 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 CGA179500 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#377921

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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 Processing Studies with Trinexapac-ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) 

PHI 

(days)

Residues 

(ppm)

Processing 

Factor1

Carrington, ND; 2008 (C13ND078468) 1x

Wheat Grain (RAC) 0.115 45 0.328

0.308

0.277

--

AGF 0.115 45 0.240

0.2302

0.77x

Bran 0.115 45 0.611

0.7072

2.17x

Flour 0.115 45 0.155

0.1082

0.43x

Middlings 0.115 45 3.67

3.292

3.392

11.3x

Shorts 0.115 45 0.150

0.1952

0.1972

0.59x

Germ 0.115 45 0.598

0.3102

0.3522

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

0.3402

0.21x

Bran 0.116 45 2.28

4.632

2.09x

Flour 0.116 45 0.900

0.5822

0.45x

Middlings 0.116 45 0.820

0.4222

0.4292

0.34x

Shorts 0.116 45 0.925

1.152

0.9482

0.61x

Germ 0.116 45 1.62

1.522

1.342

0.91x
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Table 20. Residue Data from Wheat Processing Studies with Trinexapac-ethyl as CGA179500

RAC Processed Commodity Total Rate

(lb ai/A) 

PHI 

(days)

Residues 

(ppm)

Processing 

Factor1

Carrington, ND; 2008 (C13ND078468) 5x

Wheat Grain (RAC) 0.576 45 5.57

4.90

5.73

--

AGF 0.576 45 4.77

4.032

0.81x

Bran 0.576 45 7.85

9.332

1.59x

Flour 0.576 45 2.42

2.882

0.49x

Middlings 0.576 45 2.83

2.452

2.312

0.47x

Shorts 0.576 45 0.124

0.1722

0.1672

0.03x

Germ 0.576 45 5.88

4.282

5.112

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

3.472

0.36x

Bran 0.578 45 15.8

1042, 3

14.42

13.82

1.50x

Flour 0.578 45 3.67

3.802

0.38x

Middlings 0.578 45 5.73

5.482

4.962

0.55x

Shorts 0.578 45 5.23

6.252

5.612

0.58x

Germ 0.578 45 9.78

11.12

11.62

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 used 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 parenthesis). 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 shorts (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#377921

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wheat middlings is 3.2x. These data suggest 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 values 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 residue 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 tolerance 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 References: 45898909.der, 48043709.der

In a confined rotational crop study, [14C-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. Samples of immature and mature lettuce 

were collected at 30 and 50 days after planting (DAP). The confined rotational 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 

approximately 4 months, and the minimum PBI tested for the representative root crop was 

approximately 10 months.

In another study (MRID 48043709), sandy loam soil was treated once with 14C-Trinexapac-ethyl

(66.2 μCi/mg) at a target rate of 0.312 lb ai/A (0.350 kg ai/ha); actual rates were 0.297-0.298 lb 

ai/A (0.333-0.334 kg ai/ha). Rotational crops (lettuce, radish and wheat) were planted at plant-
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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 grain 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 matrices is summarized in Tables 21a and 21b.

TABLE 21a. 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 ppm1 TRR=0.017 ppm1

%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

Accountability3<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#377921

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TABLE 21b. Summary of Characterization and Identification of Radioactive 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 ppm1 TRR= 0.011 ppm1 TRR= 0.007 ppm1 TRR= 0.004 ppm1 TRR= 0.009 ppm1

%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

Accountability3100 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 14C-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 rotational 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 trinexapac-ethyl, determined as, trinexapac (CGA179500). No permanent 

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; see Appendix II 

for tolerance calculations.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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 must 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 Meat, 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, 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/kg), rapeseed (1-2 mg/kg), sugar cane (0.05-0.1 mg/kg), sugar forage 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 definitions.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Table 22. Tolerance Summary for Trinexapac-ethyl.

Commodity Proposed Tolerance

(ppm)

Recommended Tolerance

(ppm)

Comments

PP# 0F7719

Grass, forage 1.6 1.5

Grass, hay 3.5 4.0

Grass, seed screenings 45.0 40

Grass, straw 12.0 10

Cattle, fat 0.05 0.02

Cattle, meat 0.05 0.02

Cattle, meat byproducts 0.05 0.04 Based on highest residue in 

cattle kidney

Goat, fat 0.05 0.02

Goat, meat 0.05 0.02

Goat, meat byproducts 0.05 0.04 Based on highest residue in 

cattle kidney

Horse, fat 0.05 0.02

Horse, meat 0.05 0.02

Horse, meat byproducts 0.05 0.04 Based on highest residue in 

cattle kidney

Sheep, fat 0.05 0.02

Sheep, meat 0.05 0.02

Sheep, meat byproducts 0.05 0.04 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 0.03 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#377921

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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#377921

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Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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International Residue Limits 

Trinexapac-ethyl (112602; 07/05/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 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

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

US Canada Mexico2 Codex
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 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#377921

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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 II - Tolerance Assessment Calculations
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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

OH

O

O

O

O

H3C

O

O

O

HO OH

HO OH

O O

O OH

OH

O O

OH

O

HO

O

OH

O

O

HO

HO

HO

O

O

OH

O

OH

O

HO

O

O OH
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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-ene1-carboxylic acid

OH

O

OH

HO

OH

OH

O

O

O

O

H3C
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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 it 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 paper 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 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 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 

application 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#377921

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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#377921

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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#377921

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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 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-2.

Using the tolerance spreadsheet, the 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#377921

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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#377921

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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#377921

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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#377921

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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#377921

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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 0.8ppm 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#377921

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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 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-4.

Using the tolerance spreadsheet, the recommended tolerances are 1.5 ppm for grass forage, 4.0 

ppm for grass hay, 10 ppm for grass straw, and 40 ppm for grass seed screenings.
Trinexapac-ethyl Summary of Analytical Chemistry and Residue Data DP#377921

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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#377921

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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#377921

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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#377921

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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