UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: September 12, 2013 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Trinexapac-ethyl: Human Health Risk Assessment for Registration Review. 

PC Code: 112602 

Decision Nos.: 481333 

Petition Nos.: NA 

Risk Assessment Type: NA 

TXRNo.:NA 

MRIDNo.: NA 

DP Barcode: D413570 

Registration Nos.: NA 

Regulatory Action: Registration Review 

CaseNo.:NA 

CAS No.: 95266-40-3 

40 CFR: §180.662 

Sheila Piper, Chemist/Risk Assessor\ihe..J.tu (J{pv') 

Deborah Smegal, MPH, Toxicologist . 

FROM: 

Monica Hawkins, Ph.D., M.P.H., Environmental Health Scientist Jv(_~J.i~~J.A) ~ Risk Assessment Branch VI · 

Health Effects Division (7509P) 

THROUGH: Felecia Fort, Chief 01 o ;~ Risk Assessment Branch VI Jj 

Health Effects Division (7509P) 

TO: Kaitlin Keller, Chemical Review Manager 

Risk Management and Implementation Branch 3 

Pesticide Re-Evaluation Division (7508P) 

Page I of46 
Table of Contents .................. ............................................................................. ................. .................. 1 

1.0 Executive Summary .................................................................................................................. 4 

2.0 HED Recommendations ......... .......................... ....... ............................ ............. ..... .................. .. 7 

2.1 Data Deficiencies/Conditions of Registration ........ .................... ............ .................................. 7 

2.2 Tolerance Considerations .......................................................................................................... 7 

2.2.1 Enforcement Analytical Method ...... ...................................................... ......... ... .......... ..... ......... ? 

2.2.2 International Harmonization .... .... .................................. ............ ........ .... ......... ............. ..... ......... 8 

2.2.3 Recommended Tolerances ......................................................................................................... 8 

2.3 Label Recommendations ... ........................................................................................................ 8 

2.3.1 Recommendations from Residue Reviews ................................................................................ 8 

2.3.2 Recommendations from OccupationaVResidential Assessment.. .............................................. 8 

3.0 Ingredient Profile ...... ................................................................................................................ 8 

3.1 Chemical Identity .................................................................................. ............. ....................... 8 

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

3.3 Summary ofExisting/Proposed Uses ................. ....... .... .... .... .... .... ........ .... .............. ......... ..... .. 10 

3.4 Anticipated Exposure Pathways ............................................................................................. 13 

3.5 Consideration of Environmental Justice ................................................................................. 13 

4.0 Hazard Characterization and Dose-Response Assessment.. ................................................... 13 

4.1 Hazard and Dose-Response Characterization .......................... ............................................... 13 

4.1.1 Database Summary .................................................................................................................. 14 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ............................................ 14 

4.2.1 Dermal Absorption ........................................................................ ....................................... .... 14 

4.3 Toxicological Effects .............................................................................................................. 15 

4.4 Safety factor for Infants and Children (FQPA Safety Factor) ............................................ .... 16 

4.4.1 Completeness ofthe Toxicology Database ... ............................... ............................................ 17 

4.4.2 Evidence ofNeurotoxicity and Immunotoxicity ...................................................................... l7 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .......................... 18 

4.4 .4 Residual Uncertainty in the Exposure Database ........................................................ .......... ... .18 

5.0 Dietary Exposure and Risk Assessment ....... ........ ........ .......................................................... 21 

5.1 Water Residue Profile ...................................................................... ..... .................................. 21 

5.2 Dietary Risk Assessment ................... ................... ........ .......................................................... 22 

5.2.1 Description ofResidue Data Used in Dietary Assessment ...................................................... 22 

5.2.2 Percent Crop Treated Used in Dietary Assessment.. ............................................................... 23 

5.2.3 Acute Dietary Risk Assessment.. ... .... ... ................................................................................... 23 

5 .2.4 Chronic Dietary Risk Assessment ........................................................................................... 23 

5.2.5 Cancer Dietary Risk Assessment ............................................................................................. 23 

5.2.6 Dietary Summary Table .......... ............... .................................................................................. 23 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ......................................... 24 

7.0 Aggregate Exposure/Risk Characterization ........................................... ........ ..... .... ..... .... ....... 32 

7.1 Acute Aggregate Risk .. ........... ................................................................................................ 32 

7.2 Short- and Intermediate-Term Aggregate Risk ...... ................... ............. ............ ......... ..... ....... 32 

7.3 Cancer Aggregate Risk ........................................................................................................... 33 

8.0 Cumulative Exposure/Risk Characterization .... ..................................................... ................. 33 

9.0 Occupational Exposure/Risk Pathway .................................................................................... 34 

9.1 Occupational Handler Exposure/Risk Estimates .................................................................... 34 

9.2 Occupational Post-application Exposure/Risk Estimates ....................................................... 42 

Page 2 of 46 
Page 3 of 46 

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates .......................................42

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates ...........................................42

10.0 References ............................................................................................................................... 45
Page 4 of 46 

1.0 Executive Summary

The Pesticide Re-evaluation Division requested that HED prepare a human-health risk 

assessment for trinexapac-ethyl in support of registration review. To address this request, HED 

cites the most recent trinexapac-ethyl risk assessment (D3377921, S. Piper, J. Facey, and M. 

Hawkins, 11/23/11) and has prepared this memo, which updates and expands appropriate 

sections of the November, 2012 assessment. Recent changes in dietary consumption data and 

occupational assessment policies (e.g., unit exposures, transfer coefficient, and new guidance for 

requiring/waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) 

studies) have triggered the need for an updated dietary, residential, and occupational assessment 

for trinexapac-ethyl. To take into account this new information, the following sections are 

provided: 

1) Updated acute and chronic dietary exposure and risk assessment with the 2003-2008 food 

consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health 

and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). 

2) Updated residential handlers and post-application assessments for turf products. 

3) Updated occupational handler and post-application exposure to trinexapac-ethyl from the 

currently registered products.

Hazard Characterization 

Since the previous human health risk assessment (D377921), acute and subchronic neurotoxicity 

studies have been submitted for trinexapac-ethyl. There was no evidence of neurotoxicity in the 

acute and subchronic neurotoxicity studies in rat at the highest dose tested of 2000 mg/kg and 

948/1171 mg/kg/day (male/female), respectively. Therefore, the toxicity database for 

trinexapac-ethyl is complete under the revised 40 CFR Part 158 data requirements for 

conventional pesticides. 

Endpoints of concern for the incidental oral, dermal and inhalation scenarios for children were 

not identified from the trinexapac-ethyl toxicity studies (See Section 4.0, Hazard 

Characterization). For short- and intermediate-term dermal and inhalation exposures for adults, 

the point of departure (POD) is from an oral developmental study in rabbits. The LOAEL 

(Lowest Observed Adverse Effect Level) from this study was 360 mg/kg/day based on a 

decrease in the mean number of fetuses/litter and an increase in post-implantation loss. The 

NOAEL (No Observed Adverse Effect Level) from this study was 60 mg/kg/day. A dermal 

absorption factor of 77.5 % was used for the exposure assessment based on information from a 

rat dermal penetration study (MRID 42238105). An oral study was selected for the inhalation 

route because there was no inhalation study of appropriate duration, and based on a review by 

the Hazard and Science Policy Council (HASPOC; June 20, 2013, TXR 0056699), a routespecific inhalation toxicity study is not required at this time. The level of concern (LOC) for 

occupational and non-occupational risk is for margins of exposure (MOEs) less (<) than 100. A 

body weight of 69 kg was used for the inhalation and dermal assessment since the endpoints 

were from a developmental toxicity study with fetal effects. Since the dermal and inhalation 
Page 5 of 46 

scenarios are based on the same study, they can be combined when assessing occupational and 

residential exposure. Trinexapac-ethyl is classified as “Not likely to be carcinogenic to 

humans.” 

Metabolism/Metabolites and Degradates of Concern 

The metabolism of trinexapac-ethyl in plants and animals has been adequately delineated. The 

primary degradation pathway in both livestock and plants involves trinexapac-ethyl rapidly 

undergoing hydrolysis of the ethyl ester to form trinexapac. 

The residue of concern in primary crops, rotational crops and livestock for both tolerance 

enforcement and risk assessment include free and conjugated residues of both parent trinexpacethyl and its acid metabolite, trinexapac. In drinking water, degradates of concern for risk 

assessment are trinexapac-ethyl, trinexapac, 2-(4-cyclopropyl-4-hydroxy-2-oxobutyl)succinic 

acid (CGA-313458), an open chain cyclohexane ring, and the unidentified hydroproduct M3. 

Food Residue Profile 

The residue profile for the proposed commodities is adequate. For all commodities, the 

registrants submitted adequate field trial data for parent trinexapac-ethyl as trinexapac. 

Tolerances are currently established for residues of the plant growth inhibitor, trinexapac-ethyl 

in/on various plant commodities, at levels ranging from 0.02 to 40.0 ppm as listed in e-CFR 40 

§180.662. 

Dietary Exposure and Risk 

An updated acute and chronic dietary (food and drinking water) exposure and risk assessments 

were conducted. These unrefined assessments are based on tolerance-level residues, 100% 

crop treated assumptions for all commodities, and DEEM default processing factors. The acute 

and chronic dietary risk estimates are below HED’s level of concern for all population 

subgroups, including those comprised of infants and children. Because such conservative 

assumptions were made in the assessments, HED is confident that the acute and chronic dietary 

exposure assessments do not underestimate risk to the general U.S. population or any 

population subgroup. 

Residential Exposure and Risk 

HED determined that there is a potential for residential handler and post-application exposure to 

trinexapac-ethyl from the currently registered turf products. An updated residential handler and 

post-application assessment was conducted because HED recently updated the Standard 

Operating Procedures for Residential Pesticide Exposure Assessment 

(http://www.epa.gov/opp00001/science/EPA-OPP-HED_Residential%20SOPS_Feb2012.pdf) 

and body weights to be used in all human health assessments. The combined dermal plus 

inhalation risk estimates to residential handlers do not exceed HED’s LOC for all scenarios (i.e., 

MOEs ≥ 100); MOEs ranged from 240 to 21,000,000. The short-term dermal residential postapplication MOEs ranged from 450 to 61,000, and therefore, do not exceed HED’s LOC (MOEs 
Page 6 of 46 

≥ 100). Chemical-specific TTR data are available for trinexapac-ethyl and were used in the 

residential post-application exposure assessment in conjunction with standard default 

assumptions. 

Aggregate Exposure and Risk 

The acute (females only) and chronic aggregate risks are equivalent to the corresponding dietary 

(food plus water) risks, which are not of concern. The short- and intermediate-term dermal and 

inhalation toxicological endpoints for trinexapac-ethyl are the same. The resulting aggregate 

short- and intermediate-term risk estimates for adults and children (MOE ≥ 100); therefore, the 

short- and intermediate-term aggregate risks of exposure to trinexapac-ethyl are not of concern. 

Occupational Exposure and Risk 

HED determined that there is a potential for occupational handler and post-application exposure 

to trinexapac-ethyl from the currently registered products. The occupational handler assessment 

was completed assuming the maximum label application rate for each crop. The occupational 

handler exposure and risk estimates indicate that short- and intermediate-term dermal and 

inhalation combined MOEs are not of concern to HED (i.e., MOEs ≥ 100) with baseline attire 

and/or with the addition of gloves (as required on the labels). With baseline attire and/or gloves, 

the dermal plus inhalation MOEs range from 140 to 2,100,000. 

Chemical-specific TTR data are available for trinexapac-ethyl and were used in the occupational 

post-application exposure assessment to assess turf scenarios. Chemical-specific DFR data are 

not available for trinexapac-ethyl in order to assess sugarcane, cereals (wheat, barley, oats, 

triticale), and grasses grown for seed scenarios. As specified in the revised 40 CFR Part 158 data 

requirements for conventional pesticides, a DFR study is required for trinexapac-ethyl at this 

time. The occupational post-application dermal exposure and risk estimates indicate that shortand intermediate-term MOEs are not of concern to HED (i.e., MOEs ≥ 100) on the day of 

application, except for hand-harvesting sugarcane (MOE=87) where risk estimates are of concern 

until 2 days after application (MOE=110). The occupational post-application MOEs on the day 

of application range from 87 to 43,000. Based on HED’s occupational post-application exposure 

assessment, the restricted-entry interval (REI) for hand-harvesting sugarcane was estimated to be 

2 days for short- and intermediate-term exposure. However, HED does not recommend that 

sugarcane REI’s be changed on the trinexapac-ethyl labels at this time based on two main issues. 

One, almost all sugarcane harvesting in the United States is done mechanically. Two, the 

proposed trinexapac-ethyl labels have a 28-day pre-harvest interval (PHI) for sugarcane, so hand 

harvesting should not occur until after 28 days which is protective of the estimated REIs. 

Current trinexapac-ethyl labels have no REI, 0 days, or a 4-hour REI. The trinexapac-ethyl 

technical material has been classified in Toxicity Category III for acute dermal, oral, and primary 

eye irritation, and Category IV for acute inhalation and primary skin irritation. Therefore, the 

acute toxicity categories for this chemical require a 12 hour REI under 40 CFR 156.208 (c) (2) 

(iii). 
Page 7 of 46 

Human Studies 

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from

PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) 

database; the ARTF database; and the Residential SOPs (Turf/Lawn)are (1) subject to ethics 

review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with 

applicable ethics requirements. For certain studies, the ethics review may have included review 

by the Human Studies Review Board. 

2.0 HED Recommendations

2.1 Data Deficiencies/Conditions of Registration

Dislodgeable Foliar Residue (DFR) 

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are 

required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 

Standard Operating Procedures for Residential Pesticide Exposure Assessment, HED analyzed a 

number of DFR studies and selected a new default value for the fraction of the application rate 

available to be dislodged after a foliar application (FAR). This default value is 25% and is based 

on an analysis of 19 DFR studies where the FAR value ranged from 2% to 89%. This value is 

recommended for use in both residential and occupational post-application assessments. Of the 

analyzed DFR studies, the maximum FAR value seen was 89% or 3.6 times higher than the 

default residue transfer value. Therefore, the HED has decided that a calculated MOE of 

approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 100) 

using the default dislodged residue values would provide an adequate margin of safety for any 

potentially higher residues seen in a chemical-specific DFR study (Guidance for 

Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) 

Studies. 6/7/2012, Exposure Science Advisory Council). A DFR study will be required for 

future assessments for trinexapac-ethyl. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method 

An adequate enforcement method is available for trinexapac-ethyl, Method GRM020.01A, 

which utilizes high performance liquid chromatography with triple-quadrupole mass 

spectrometry (LC-MS/MS). The new method includes a strong acid hydrolysis/extraction 

procedure to release both “free” and “conjugated” residues of CGA179500 from field grown 

grass commodities. The reported limit of quantitation (LOQ) is 0.010 ppm. The method has 

been adequately validated. Also, trinexapac-ethyl was evaluated using the FDA multiresidue 

method Protocols C and D, and its acid metabolite, trinexapac, was evaluated using Protocol B. 
Page 8 of 46 

These data indicate FDA multi-residue methods are not suitable for determining residues of 

trinexapac-ethyl and trinexapac in plant commodities. 

2.2.2 International Harmonization 

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), 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). 

2.2.3 Recommended Tolerances 

Tolerances are established for residues of the plant growth regulator trinexpac-ethyl, including 

its metabolite and degradate, in or on the commodities in the 40CFR 180.662. For plant and 

livestock commodities, the tolerances should be established as follows: 

Tolerances are established for residues of trinexapac-ethyl, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring 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. 

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews 

The label must be modified to specify a 30-day plantback restriction for cereal grains and leafy 

vegetables, and prohibit the planting of all other crops not listed on the label. 

 

2.3.2 Recommendations from Occupational/Residential Assessment 

PRD should ensure the proper restricted entry intervals (REIs) are put in place considering the 

post-application assessment, the acute toxicity of trinexapac and the criteria for 12-hr REIs on 

the labels to reflect these requirements. 

3.0 Ingredient Profile

3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature 
Page 9 of 46 

Table 3.1. Test Compound 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 

3.2 Physical/Chemical Characteristics

Trinexapac-ethyl has a relatively low octanol/water partition coefficient. At pH 5.3, the log KOW

value is 2.44 (KOW = 275). Trinexapac-ethyl has a low potential to leach into groundwater and is 

not expected to be volatile because of its low vapor pressure (2.16 x 10-3 Pa at 25o

C). See Table 

3.2 for a listing of trinexapac-ethyl physical and chemical properties. 

OH

O

O

O

O

H3C

O

O

O

HO OH
Page 10 of 46 

Table 3.2. Physical and Chemical 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) 2.16x 10-3 Pa 

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 

3.3 Summary of Existing/Proposed Uses

Trinexapac-ethyl is a cyclohexadione plant growth regulator that is marketed as an emulsifiable 

concentrate, wettable powder packed in water-soluble bags, granule, and as a technical chemical 

used for formulation only. Syngenta Crop Protection has registered trinexapac-ethyl for multiple 

end-use products on turf areas such as sod farms, golf courses, sport fields, cemeteries and 

similar areas, and on grasses grown for seed, sugarcane, and cereals (wheat, barley, oats, 

triticale). The label-required personal protective equipment (PPE) for occupational applicators 

and handlers is a long-sleeved shirt, long pants, shoes, and socks, chemical-resistant gloves, and 

protective eyewear. The currently registered uses and application rates are summarized in Table 

3.3. 

Table 3.3. Trinexapac-ethyl Use Patterns and Formulations 

Applic. Timing, 

Type, and 

Equip. 

Formulation 

[EPA Reg. 

No.] 

Applic. 

Rate (lb 

ai/A) 

Max. Seasonal 

Applic. Rate 

(lb ai/A) 

Max. 

Applic. 

per 

Season 

REI Use Directions and 

Limitations 

Turf 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Hand 

Gun Sprayers 

12% ai, EC 

Primo Liquid 

(EPA Reg. No. 

100-729) 

0.36 lb 

ai/A 

(0.017 lb 

ai/gallon; 

0.000008 

lb ai/ft2

) 

0.36 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Spray 

Gun 

25.0 % ai, 

Primo WSB 

WP in Water 

Soluble Bag 

0.34 lb 

ai/A 

(0.016 lb 

ai/gallon) 

0.34 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 
Page 11 of 46 

Table 3.3. Trinexapac-ethyl Use Patterns and Formulations 

Applic. Timing, 

Type, and 

Equip. 

Formulation 

[EPA Reg. 

No.] 

Applic. 

Rate (lb 

ai/A) 

Max. Seasonal 

Applic. Rate 

(lb ai/A) 

Max. 

Applic. 

per 

Season 

REI Use Directions and 

Limitations 

(EPA Reg. No. 

100-752) 

Turf (Edging/Banding)

Spreader, Shaker 

Can 

.01 %-1.0 % ai, 

Lawn Primo F, 

Granule, (EPA 

Reg. No. 

100-931) 

0.88 lb 

ai/A 

(0.00002 

lb ai/ft2

) 

0.88 lb ai/A Multiple 0 days 

Be sure the lawn has adequate 

fertility before using the 

product. 

Backpack 

Sprayers, Hand 

Sprayers, Boom 

Sprayers, Spray 

Guns 

12% ai, EC 

Primo Liquid 

(EPA Reg. No. 

100-729) 

0.73 lb 

ai/A 0.73 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Spray 

Gun 

25.0 % ai, 

Primo WSB, 

WP in Water 

Soluble Bag 

(EPA Reg. No. 

100-752) 

0.68 lb 

ai/A 0.68 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Turf and Edging/Banding 

Spreader, Shaker 

Can 

0.39% ai, 

The Andersons 

0.39% 

Trinexapacethyl + 

Fertilizer, 

Granule, 

(EPA Reg. No. 

9198-246) 

0.88 lb 

ai/A 

0.88 lb ai/A Multiple 0 days Do not apply this product to 

grasses not listed on the label. 

Sod Farm 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Hand 

Gun Sprayers 

12% ai, EC 

Primo Liquid 

(EPA Reg. No. 

100-729) 

0.36 lb 

ai/A 0.36 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Spray 

Gun, Aerial, 

Chemigation 

25.0 % ai, 

Primo WSB, 

WP in Water 

Soluble Bag 

(EPA Reg. No. 

100-752) 

0.34 lb 

ai/A 0.34 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Golf Course Fairways

Spreader, Shaker 

Can 

0.39% ai, 

The Andersons 

0.39% 

Trinexapacethyl + 

Fertilizer, 

Granule, 

(EPA Reg. No. 

0.44 lb 

ai/A 0.44 lb ai/A 0 days Do not apply this product to grasses not listed on the label. 
Page 12 of 46 

Table 3.3. Trinexapac-ethyl Use Patterns and Formulations 

Applic. Timing, 

Type, and 

Equip. 

Formulation 

[EPA Reg. 

No.] 

Applic. 

Rate (lb 

ai/A) 

Max. Seasonal 

Applic. Rate 

(lb ai/A) 

Max. 

Applic. 

per 

Season 

REI Use Directions and 

Limitations 

9198-246) 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Hand 

Gun Sprayers 

12% ai, EC 

Primo Liquid 

(EPA Reg. No. 

100-729) 

0.18 lb 

ai/A 0.18 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Spray 

Gun 

25.0 % ai, 

Primo WSB, 

WP in Water 

Soluble Bag 

(EPA Reg. No. 

100-752) 

0.17 lb 

ai/A 0.17 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Golf Course Greens 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Hand 

Gun Sprayers 

11.3% ai, 

Microemulsion 

Concentrate 

Primo Maxx 

(EPA Reg. No. 

100-937) 

0.07 lb 

ai/A 0.07 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Spreader, Shaker 

Can 

.01 %-1.0 % ai, 

Lawn Primo F, 

Granule, (EPA 

Reg. No. 

100-931) 

0.07 lb 

ai/A 0.07 lb ai/A Multiple 0 days 

Be sure the lawn has adequate 

fertility before using the 

product. 

Back Pack, Hand 

Sprayers, Boom 

Sprayers, Spray 

Gun 

25.0 % ai, 

Primo WSB, 

WP in Water 

Soluble Bag 

(EPA Reg. No. 

100-752) 

0.05 lb 

ai/A 0.05 lb ai/A Multiple 0 days 

Do not apply this product 

through any type of irrigation 

system. 

Grasses Grown For Seed 

Aerial, Ground, 

Chemigation 

12 % 

Palisade EC, 

EC, 

(EPA Reg. No. 

100-949) 

0.5 lb ai/A 0.5 lb ai/A 2 12 hours PHI = 35 days 

Sugarcane 

Aerial, Ground, 

Chemigation 

12 % 

Palisade EC, 

EC, 

(EPA Reg. No. 

100-949) 

0.31 lb 

ai/A 0.31 lb ai/A 2 12 hours PHI = 28 days 

Cereals (Wheat, Barley, Oats, Triticale) 

Aerial, Ground, 

Chemigation 

12 % 

Palisade EC, 

EC, 

(EPA Reg. No. 

100-949) 

0.1 lb ai/A 0.11 lb ai/A 2 12 hours PHI = 45 days. 

Several of the trinexapac-ethyl labels did not provide the pounds (lb) active ingredient (ai) per gallon of product; 

therefore, HED made assumptions in order to convert the rates to lb ai/A. 
Page 13 of 46 

3.4 Anticipated Exposure Pathways

PRD requested that HED perform an assessment of human health risk to support for trinexapacethyl on cereal grains, sugarcane, turf grass, sod farms, golf courses, and residential lawns in 

support of registration review. Humans might be exposed to trinexapac-ethyl in food and drinking 

water because trinexapac-ethyl may be applied directly to growing crops. In addition, these 

applications can result in trinexapac-ethyl reaching surface and groundwater, both of which can 

serve as sources of drinking water. The uses on turf grass result in the potential for both residential 

and occupational exposures. In addition, because of the agricultural uses, applicators might be 

exposed while handling the pesticide prior to application, mixing/loading the pesticide, and during 

application. There is a potential for post-application exposure for workers re-entering treated fields. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to 

Address Environmental Justice in Minority Populations and Low-Income Populations,” 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide 

exposures that are based on patterns of that subgroup’s food and water consumption, and activities 

in and around the home that involve pesticide use in a residential setting. Extensive data on food 

consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by 

Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, 

ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to 

smaller, specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas postapplication are evaluated. Further considerations are 

currently in development as OPP has committed resources and expertise to the development of 

specialized software and models that consider exposure to bystanders and farm workers as well as 

lifestyle and traditional dietary patterns among specific subgroups. 

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Hazard and Dose-Response Characterization

The acute toxicity for trinexapac-ethyl technical formulation was classified as Toxicity Category 

III for acute oral, dermal, and eye irritation, and IV for acute inhalation and skin irritation. Table 

4.1 presents a summary of the acute toxicity information for trinexapac-ethyl. 
Page 14 of 46 

Table 4.1. Acute Toxicity Profile - Trinexapac-ethyl (97%) 

Guideline 

No. Study Type MRID Results Toxicity Category 

870.1100 Acute oral [rat] 41563901 

♂ LD50 = 4613 mg/kg 

♀ LD50 = 4212 mg/kg 

Combined LD50 = 4458 mg/kg 

III 

870.1200 Acute dermal [rabbit] 41563910 LD50 > 4000 mg/kg III 

870.1300 Acute inhalation [rat] 41563912 LC50 ≥ 5.3 mg/L IV 

870.2400 Acute eye irritation [rabbit] 41563914 Minimal irritant; cleared by 72 hours III 

870.2500 Acute dermal irritation [rabbit] 41563916 Slightly irritating; cleared by day 7 IV 

870.2600 Skin sensitization [guinea pig] 41869522 Not a dermal sensitizer N/A 

4.1.1 Database Summary 

The toxicology database for trinexapac-ethyl is complete for risk assessment in support of 

registration review. Available toxicity studies are detailed in the following section and a brief 

summary of the findings is discussed in section 4.3, Toxicological Effects. 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Absorption: Trinexapac-ethyl was rapidly and extensively absorbed in both sexes of rat 

following single or repeat low-dose (0.97 mg/kg bw) administration and single high-dose (166 

mg/kg bw) administration. Greater than 95% of the administered dose was absorbed following 

single or repeat low-dose administration and single high-dose administration. Data suggests that 

there was very little or no biliary absorption. Distribution: The highest residue levels were 

observed in the fat, lungs, kidneys and liver; however, mean recovery of radioactivity in 

tissues/carcass at sacrifice (at 168 h post-dosing) was less than 0.3% of administered dose for all 

dose groups indicating little potential for accumulation. Metabolism: The major component in 

urine and fecal extracts was identified as 4-cyclopropyl-(hydroxy-methylene)-3,5-dioxocyclohexanecarboxylic acid, the free acid derivative of trinexapac-ethyl resulting from 

hydrolysis of the ester bond of the parent compound accounting for approximately 82–91.6% of 

the administered dose. The only other residue found (found in fecal extract only) was identified 

as the parent compound, accounting for less than 0.1% of the administered dose. Excretion: 

Excretion was rapid, with the majority of radioactivity being eliminated within 12 h post-dosing 

via urine (greater than 85% of the administered dose at the low and high dose) and within 24 h 

post-dosing via feces (0.56–1.43 and 0.80–2.01% at the low and high dose, respectively). The 

major route of excretion was via urine, accounting for approximately 95% of administered dose 

at both dose levels. Fecal excretion accounted for approximately 1.0–2.4% of administered dose 

at both dose levels. By 72 hr less than 0.01% of the administered dose was recovered in expired 

air. Data suggest that there was very little or no biliary excretion. Significant qualitative 

differences were not found in absorption, distribution, metabolism or excretion of trinexapacethyl between the sexes, between single and repeat low-dose administration, or between single 

low-dose and high-dose administration. These results indicate that toxicity of both the parent 

and acid metabolite has been accounted for in the submitted toxicity studies. 

4.2.1 Dermal Absorption 
Page 15 of 46 

A single dermal dose of 0.01, 0.1, or 1.0 mg/cm2 14C-trinexapac-ethyl administered to male rats 

was rapidly absorbed, distributed and eliminated (MRID 42238105). The amount absorbed 

increased with duration of exposure. The average 14C- trinexapac-ethyl absorbed within 24 hours 

was 56.8, 66.7, and 33.8% of the applied dose for the low-, mid-, and high- dose groups, 

respectively. Recovery of the applied dose was 97-117% and most was recovered from the skin 

washes and urine. A dermal absorption factor of 77.5% was estimated based on the sum of 

56.5% absorbed after 10 hours in the low dose group (0.01 mg/cm2), in addition to 21% of 

applied dose that was associated with the application site after wash. 

 

4.3 Toxicological Effects

The acute toxicity of the technical material is low via the oral, dermal, or inhalation routes of 

exposure (Categories III-IV), and it is not a dermal sensitizer. 

Trinexapac-ethyl is a low acute toxicity chemical with systemic effects occurring at or well 

above 300 mg/kg/day in subchronic and lifetime dosing studies. There is, however, evidence of 

increased qualitative and quantitative susceptibility in the rat (increased incidence of 

asymmetrical sternebrae) and rabbit (decreased number of live fetuses/litter and increased postimplantation loss) developmental studies, but only at relatively high doses (300 – 1,000 

mg/kg/day). Qualitative sensitivity was observed in the 2-generation reproduction study but only 

above the limit dose (1,000 mg/kg/day). Decreased pup survival when analyzed with sexes 

combined resulted in statistical significance (5-7%), but was not significant when analyzed 

separately. Further evaluation of the individual litters suggested that one or two litters were not 

the cause of the reduced pup survival at the highest dose tested. Reproductive toxicity was not 

observed up to the limit dose. Refer to Table 4.3 for a comparison of the effects across toxicity 

studies. 

Looking across the available toxicity studies, the dog appears to be the most sensitive species. In 

adult animals, no systemic adverse effects were seen in rats, rabbits, or mice below the limit dose 

(1,000 mg/kg/day) following subchronic or chronic oral exposure. In the dogs, however, 

decreased body weight gain and food consumption, diffuse thymic atrophy, and changes in the 

epithelial cells of the renal tubules were seen in the 90-day dog study at 516/582 mg/kg/day 

(males/females). Following chronic exposure, dose-related neuropathology of the brain was seen 

at ≥365/357 mg/kg/day in male and female dogs, respectively. The lesions remained confined to 

the supporting cells in the central nervous system and did not progress to more advanced or more 

extensive damage of the nervous tissue. They were not associated with other neuropathological 

findings or overt neurological signs, so their biological significance is unknown. Similar lesions 

were not observed in the rat or mouse following subchronic or chronic dietary exposure, and 

there was no other evidence in any other species tested to indicate a neurotoxicity potential. 

There was no evidence of neurotoxicity in the acute and subchronic rat neurotoxicity studies. 

Furthermore, the brain lesions observed in the chronic dog study are not likely to develop from a 

short-term exposure and were not observed in either the rat or mouse short-term studies. 

The combined chronic toxicity/carcinogenicity study in the rat did not demonstrate an increase in 

any tumor type that would be relevant to humans. The observation of squamous cell carcinomas 

in the non-glandular portion of the stomach of two males at 806 mg/kg/day does not provide 
Page 16 of 46 

reasonable evidence of a possible deleterious effect of trinexapac-ethyl on the pharynx and/or 

esophagus (non-glandular areas) of the human because trinexapac-ethyl would not be in contact 

with the human tissues for a significant period of time compared to the length of time with which 

it would have been in contact with the rat stomach. Follicular adenocarcinoma of the thyroid 

was significantly increased in males (5%) at 806 mg/kg/day, but was within the historical control 

range. In the mouse, there was no evidence of carcinogenicity. The mutagenicity database is 

complete, with no evidence of mutagenicity. The cancer classification for trinexapac-ethyl is 

“Not likely to be carcinogenic to humans.” 

Table 4.3. Comparison of NOAELs/LOAELs for consideration in risk assessment for trinexapacethyl 

Study NOAEL 

mg/kg/day 

LOAEL 

mg/kg/day Endpoint

Rat Developmental 

Maternal 1000 >1000 none 

Developmental 200 1000 

Based on increased incidence of 

asymmetrically-shaped sternebrae 

Rabbit Developmental 

Maternal 360 (HDT) >360 none 

Developmental 60 360 (HDT) 

Based on a decrease in the mean number 

of fetuses/litter and an increase in postimplantation loss 

2-Generation Reproduction- Rat

Parental 594 1212 

Based on reduced premating and gestation 

body weight/body-weight gain and food 

consumption 

Offspring 594 1212 

Based on decreased F1 postnatal survival 

and reduced pup body weights in both 

generations [both sexes]. 

Chronic Dog

Adult males and 

females 31.6 357 

Based on elevated serum cholesterol 

values in females, mucoid feces in females 

and bloody feces in both sexes, and 

minimal, focal vacuolation of the dorsal 

medial hippocampus and/or lateral 

midbrain in both sexes. 

4.4 Safety factor for Infants and Children (FQPA Safety Factor)
Page 17 of 46 

The existing use pattern for trinexapac-ethyl could potentially result in dietary (various crops) 

and residential (turf) exposure to infants and children. Thus, FQPA hazard considerations were 

addressed in HED’s evaluation of the toxicology database. HED recommends that the 10x 

FQPA Safety Factor (for the protection of infants and children) be reduced to 1x. The 

toxicological database for trinexapac-ethyl is complete with regard to pre-and postnatal toxicity, 

immunotoxicity and neurotoxicity studies, and there are no residual uncertainties. Additionally, 

the dietary exposure assessment is based on conservative, health-protective assumptions that 

ensure that exposures to trinexapac-ethyl are not underestimated. These assumptions include 

tolerance-level residues and 100% crop treated estimates for all commodities. Furthermore, 

conservative, upper-bound assumptions were used to determine exposure through drinking water 

and residential sources, such that these exposures have not been underestimated. 

4.4.1 Completeness of the Toxicology Database 

The toxicology database for trinexapac-ethyl is complete for risk assessment. There are 

acceptable studies available for toxicity endpoint selection; they include: 

The Hazard and Science Policy Council (HASPOC; June 20, 2013, TXR 0056699) concluded 

based on a weight of evidence (WOE) approach that a subchronic inhalation study is not needed 

at this time. 

There are no residual uncertainties in the toxicological database and EPA has determined that an 

additional database uncertainty factor for lack of all guideline studies is not needed at this time. 

The rationale is based on the following: 1) although there is evidence of brain neurotoxicity in 

the chronic dog study, there are clear NOAELs/LOAELs for this effect; 2) there is a large dose 

spread in the chronic dog study such that the PoD or NOAEL from the chronic dog study is 10-

fold lower than the dose at which neuropathology is observed and therefore sufficiently 

protective; 3) there are no concerns for children via incidental oral ingestion exposures since no 

endpoint of concern (i.e. non in-utero) was identified in the available studies; and 4) the 

registrant has submitted the acute neurotoxicity study (in review) and is currently conducting the 

subchronic neurotoxicity study. Both the ACN and SCN showed no signs of neurotoxicity at 

the highest doses tested (NOAELs of2000 mg/kg, and 948/1171 mg/kg/day, respectively). 

Currently, an oral toxicity study is being used to assess inhalational exposure. However, with the 

oral NOAEL currently used for inhalation risk assessment, all of the occupational and residential 

inhalation MOEs are well above the LOC and the conventional 100X safety factor has been 

applied to inhalation risk assessments. Therefore, even if an inhalation study were to provide a 

lower point of departure than the oral study, it's not expected to have a significant impact on 

aggregate risk.

4.4.2 Evidence of Neurotoxicity and Immunotoxicity 

There was no evidence of neurotoxicity in the acute and subchronic neurotoxicity studies in rats 

at the highest dose tested of 2000 mg/kg and 948/1171 mg/kg/day (male/female), respectively. 
Page 18 of 46 

Dose-related neuropathology characterized as focal bilateral vacuolation of the dorsal medial 

hippocampus and/or lateral midbrain in both sexes was observed at study termination in the 

chronic dog study at the two highest doses tested (356 mg/kg/day: 3/8 dogs and 727 mg/kg/day: 

8/8 dogs in the mid- and high dose groups, respectively). The vacuolation was associated with 

the astrocytes and oligodendrocytes. The lesions remained confined to the supporting cells in the 

CNS and did not progress to more advanced or more extensive damage of the nervous tissue. 

The lesions were not associated with other neuropathological findings or overt neurological 

signs. The biological significance of these lesions is not known. Similar microscopic lesions in 

the brain were not reported in the 90-day dog study, although, there was an inconsistency in the 

level of screening of the brain in the 90- day study. It is highly unlikely, however, that lesions 

would develop within a short-term (1-30 days) period of exposure. Furthermore, similar lesions 

were not observed in the rat or mouse following subchronic or chronic dietary exposure, and 

there was no other evidence in any species tested to indicate a neurotoxicity potential. 

An immunotoxicity study (MRID 48444101) in mice was submitted for trinexapac-ethyl. This 

study satisfies the guideline requirement for an immunotoxicity study (OPPTS 870.7800). There 

were no treatment related effects on mortality, clinical observations, body weights, food 

consumption, thymus and spleen weights, or macroscopic findings in the splenic antibodyforming cell (AFC) and the Natural Killer cell (NKC) groups. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal 

Evidence of increased qualitative and quantitative susceptibility of the offspring was seen only at 

high doses in the developmental rat and rabbit studies, and reproduction study. Developmental 

toxicity in the rat was only observed at the limit dose (increased incidence of asymmetrical 

sternebrae at 1,000 mg/kg) in the absence of maternal toxicity. In the rabbit, no maternal toxicity 

was demonstrated at the highest dose tested [360 mg/kg/day], but there was a decrease in the 

mean number of fetuses/litter and an increase in post-implantation loss at this dose level. 

However, clearly identified no effect levels were established in both the rat and rabbit 

developmental studies. Reproductive toxicity was not observed in the rat reproduction study, but 

decreased pup survival and decreased pup body weight/body-weight gain during lactation were 

observed above the limit dose with only reduced body weight and food consumption observed in 

the parental animals (>1200 mg/kg/day). 

Although, there is evidence of susceptibility in the rat and rabbit developmental studies and in 

the 2-generation rat reproduction study, these effects only occurred at the highest doses tested 

(360-1200 mg/kg/day), for each study, and there were clearly identified NOAELs (60-593 

mg/kg/day) for each fetal/offspring effect. 

4.4.4 Residual Uncertainty in the Exposure Database 

There are no residual uncertainties in the exposure database. Since the dietary and non-dietary 

exposure estimates were based on several conservative assumptions, HED does not believe that 

the exposure estimates are underestimated. The dietary exposure assessment is based on 

conservative, health-protective assumptions that ensure that exposures to trinexapac-ethyl are not 

underestimated. These assumptions include tolerance-level residues and 100% crop treated 
Page 19 of 46 

estimates for all commodities. Actual exposures and risks from trinexapac-ethyl will likely be 

lower. Furthermore, conservative, upper-bound assumptions were used to determine exposure 

through drinking water and residential sources, such that these exposures have not been 

underestimated. 

4.4.5 Dose-Response Assessment 

The short- and intermediate-term dermal and inhalation endpoints selected for adults are not 

applicable to children because the adult endpoints are based on in utero effects. HED reviewed 

the full toxicological database for trinexapac-ethyl in an attempt to select endpoints for children 

for the dermal and inhalation exposure scenarios; however, no appropriate endpoints were 

identified for these scenarios based on the following reasons: 

 dermal irritation effects are mild after 21/28 days of exposure in the rabbit study, 

 dermal irritation effects after a single exposure disappear after seven days, 

 there are no systemic effects up to the limit dose in the dermal rabbit study, 

 there are no adverse toxicological effects (at doses close to the limit dose of 1000 

mg/kg/day) in the 2-generation reproductive study in rats or in the 

chronic/carcinogenicity studies in rats and mice, 

 there is no maternal toxicity in the developmental toxicity studies in both rats and 

rabbits, and 

 there are no identifiable endpoints for the oral studies in the rat or rabbit. 

An endpoint for children for the incidental oral exposure scenario was also not identified from 

the available trinexapac-ethyl toxicity studies and the rationale for this conclusion is based on the 

following weight of evidence considerations: 

 the toxicity observed during the appropriate duration of concern (short/intermediate 

term) were observed only at high doses [LOAELs = 900 mg/kg/day in the dog, 1000 

mg/kg/day in the rat, and 1212 mg/kg/day in the reproduction study], 

 the brain lesions observed in the chronic dog study are not appropriate for this 

scenario since the brain lesions were seen only at termination (i.e. after exposure for 

1-year) and toxicity observed after chronic exposure is not appropriate for application 

to the short/intermediate term scenarios, 

 the brain lesions observed in the chronic study are not expected to occur after short 

term exposure due to the lack of similar lesions or associated toxicity (i.e., clinical 

neurologic signs) in the 90-day studies in rats or dogs, 

 the cause for concern for the brain lesions is low because of the minimal lesion 

severity, lack of associated changes (i.e., gliosis, myelin loss astrocyte hypertrophy, 

neuronal necrosis etc), and the non-specific nature of the lesions (i.e., focal 

vacuoles), 

 the overall toxicity profile of this chemical clearly shows that toxicity is observed 

only at high doses (lowest LOAEL = 360 mg/kg/day in the chronic dog study), and 

 the in utero endpoint identified in the rabbit study is not appropriate for this 

population of concern (children) (D392798, M.Hawkins, 11/23/2011). 
Page 20 of 46 

The toxicological doses and endpoints for trinexapac-ethyl are shown in Table 4.4.5 below. 

Table 4.4.5. Summary of Toxicological Doses and Endpoints for Trinexapac-ethyl for use in 

Human Health Risk Assessments. 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/ 

FQPA 

Safety 

Factors 

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary

(General 

Population, 

including 

Infants and 

Children) 

No appropriate endpoint for the general population including infants and children 

Acute Dietary 

(Females 13-49 

years of age) 

NOAEL = 

60 mg/kg 

UFA= 10x 

UFH = 10x 

FQPA SF= 

1x 

Acute RfD = 

0.6 mg/kg 

aPAD = 0.6 

mg/kg 

Developmental rabbit study 

MRID 41869524 

LOAEL = 360 mg/kg, based on a 

decrease in mean number of 

fetuses/litter and an increase in 

post-implantation loss 

Chronic 

Dietary (All 

Populations) 

NOAEL= 

31.6 

mg/kg/day 

UFA= 10x 

UFH = 10x 

FQPA SF= 

1x 

Chronic RfD = 

0.32 

mg/kg/day 

cPAD = 0.32 

mg/kg/day 

Chronic oral toxicity study – dog 

MRID 42779402/ 42779401 

LOAEL = 357 mg/kg/day, based 

on elevated serum cholesterol 

values in females, mucoid feces 

in females and bloody feces in 

both sexes, and minimal, focal 

vacuolation of the dorsal medial 

hippocampus and/or lateral 

midbrain in both sexes 

Incidental 

Oral 

(Short and 

IntermediateTerm ) 

No appropriate endpoint for the incidental oral scenario for children 
Page 21 of 46 

Table 4.4.5. Summary of Toxicological Doses and Endpoints for Trinexapac-ethyl for use in 

Human Health Risk Assessments. 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/ 

FQPA 

Safety 

Factors 

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment 

Study and Toxicological Effects 

Dermal & 

Inhalation 

Short- and 

Intermediateterm (adults 

only) 

NOAEL= 

60 

mg/kg/day 

Dermal 

absorption 

rate = 77.5% 

of oral 

absorption 

Inhalation 

absorption 

rate assumed 

to be 

equivalent to 

oral

UFA= 10x 

UFH = 10x 

FQPA SF= 

1x 

Residential 

LOC for MOE 

= 100 

Occupational 

LOC for MOE 

= 100 

Developmental rabbit study 

MRID 41869524 

LOAEL = 360 mg/kg, based on a 

decrease in mean number of 

fetuses/litter and an increase in 

post-implantation loss 

Dermal & 

Inhalation 

Short- and 

Intermediateterm 

No appropriate endpoint for the dermal and inhalation scenario for children 

Cancer (oral, 

dermal, 

inhalation) 

Classification: “Not likely to be Carcinogenic to Humans” 

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. 

5.0 Dietary Exposure and Risk Assessment 

5.1 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED) in the following memorandum: “TrinexapacEthyl Drinking Water Assessment to Support Registration Review” (C. Koper, D409833, 

03/11/13) and incorporated directly into the dietary assessment. 
Page 22 of 46 

A Tier II screening-level drinking water assessment was conducted to support the human 

health risk assessment for the first food use registration for trinexapac-ethyl on cereals (wheat, 

barley, oats) and sugarcane. Since there are no recent actions, the estimated drinking water 

concentrations (EDWCs) generated for turf use still hold precedence. For surface water, a 

foliar ground application to Pennsylvania turf yielded the highest EDWCs. The 1-in-10 yr 

annual peak (acute) concentration was 12.61 μg/L, the 1-in-10 yr annual mean (chronic) 

concentration was 1.56 μg/L and the 30-year annual mean (cancer chronic) concentration was 

1.04 μg/L. For groundwater, based on the highest annual use rate for turf, the SCI-GROW 

model estimated the trinexapac ethyl concentration at 0.009 μg/L. 

Based on the ROCKS memorandum (D390121, 7/12/11), the parent ester including its free 

acid CGA-179500, CGA-313458, an open chain cyclohexane ring and an unidentified 

hydroproduct M3 should be included in a Total Toxic Residue (TTR) approach for the drinking 

water assessment. 

Water residues were incorporated in the DEEM-FCID into the food categories “water, direct, 

all sources” and “water, indirect, all sources.” Table 5.1 provides a summary of the Tier 2 

modeled drinking water concentrations. The model and its description are available at the EPA 

internet site: http://www.epa.gov/oppefed1/models/water/. 

Table 5.1. Trinexapac-Ethyl Estimated Drinking Water Concentrations (EDWCs)1 for 

Surface Water and Ground Water based on Selected Crop Scenarios 

Label Use 

PRZM/EXAMS 

Scenario1

(first app date) 

Method2

Maximum 

Application Rate 

(interval between 

applications) 

1-in-10 

year 

acute 

(μg/L)

1-in-10 

year 

chronic 

(μg/L)

30- year 

average 

(μg/L) 

Primo® WSB 

Surface Water 

Turf 

FL Turf 

(Feb 15 – foliar) G 8 app @ 0.34 lb a.i./acre 10.16 1.22 0.84 

PA Turf 

(April 15 – foliar) G 8 app @ 0.34 lb a.i./acre 12.61 1.56 1.04 

Ground Water 

SCIGROW Turf -- 8 app @ 0.34 lb a.i./acre 0.009 0.009 0.009 

1 For surface water (PRZM/EXAMS), EDWC values adjusted with a Percent Cropped Area (PCA) factor of 1.0. For 

ground water (SCI-GROW), no PCA adjustment was utilized. 

2 G = ground application. 

Bold numbers denote maximum EDWC values. 

5.2 Dietary Risk Assessment 

5.2.1 Description of Residue Data Used in Dietary Assessment 
Page 23 of 46 

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 3.16 

which uses food consumption data from the U.S. Department of Agriculture’s (USDA’s) 

National Health and Nutrition Examination Survey, What We Eat in America 

(NHANES/WWEIA). 

The acute and chronic analyses are based on tolerance-level residues, 100% crop treated 

assumptions for all commodities and default processing factors. The drinking water estimates 

provided by EFED are modeled estimates, and were generated using the most conservative 

model available for the registered crops. HED is confident that the acute and chronic dietary 

exposure assessments significantly overestimate risk to the general U.S. population and various 

population subgroups. 

5.2.2 Percent Crop Treated Used in Dietary Assessment 

As stated above, the acute and chronic assessments were both based on the assumption that 

100% of all commodities with trinexapac-ethyl recommended tolerances will be treated. 

5.2.3 Acute Dietary Risk Assessment 

The acute dietary exposure was estimated for females 13-49 years old only, since an acute 

endpoint of concern was not identified for the general U.S. population. The acute dietary 

exposure estimate for females 13-49 years old is 0.014057 mg/kg/day (2% of the acute 

population adjusted dose (aPAD)).

5.2.4 Chronic Dietary Risk Assessment 

The chronic dietary exposure and risk estimates are conservative since they assume that 100% of 

crops are treated and that the residues are present at the recommended tolerance levels. 

Combined chronic dietary exposure estimates for food and drinking water are well below HED’s 

level of concern. Using the DEEM-FCID software, dietary exposure is estimated at 0.007535 

mg/kg/day for the general U.S. population, which is equivalent to 2% of the chronic population 

adjusted dose (cPAD), and 0.019416 mg/kg/day, equivalent to 6% of the cPAD for children 1-2 

years old, the population subgroup with the highest estimated chronic dietary exposure to 

trinexapac-ethyl. Results for all population subgroup are summarized in Table 5.2.6, below.

5.2.5 Cancer Dietary Risk Assessment 

Trinexapac-ethyl is classified as “Not Likely to be Carcinogenic to Humans.” Therefore, a 

cancer dietary exposure assessment was not conducted. 

5.2.6 Dietary Summary Table 

Table 5.2.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for 

Trinexapac-ethyl
Page 24 of 46 

Population Subgroup 

Acute Dietary1

(95th% Percentile) Chronic Dietary Cancer 

Dietary 

Exposure 

(mg/kg/day) 

% 

aPAD 

Dietary 

Exposure 

(mg/kg/day) 

% cPAD

Dietary 

Exposure 

(mg/kg/day) 

Risk 

General U.S. 

Population 

 0.007535 2 

N/A N/A 

All Infants (< 1 year 

old) 0.006360 2 

Children 1-2 years old 0.019416 6 

Children 3-5 years old 0.018520 6 

Children 6-12 years old 0.013294 4 

Youth 13-19 years old 0.007701 2 

Adults 20-49 years old 0.006093 2 

Adults 50+ years old 0.005137 2 

Females 13-49 years 

old1

0.014057 2 0.005741 2 

1

 aPAD=0.6 mg/kg/day for females 13-49 only (no appropriate endpoint for general US population 

including infants and children) and cPAD=0.32 mg/kg/day. Not likely to be Carcinogenic to Humans 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 

Trinexapac-ethyl is currently registered for use on turf; updated residential handler and 

residential post-application exposure assessments were conducted according to HED’s 2012 

Residential Standard Operating Procedures (SOPs)1

. 

6.1 Residential Handler Exposure/Risk Characterization

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment. 

 

The quantitative exposure/risk assessment developed for residential handlers is based on the 

following scenarios: 

 

1 Available: http://www.epa.gov/pesticides/science/residential‐exposure‐sop.html
Page 25 of 46 

 Mixing/Loading/Applying Liquid with Hose-End Sprayer, 

 Mixing/Loading/Applying Liquid with Manually-Pressurized Hand-wand, 

 Mixing/Loading/Applying Liquid with Sprinkler Can, 

 Mixing/Loading/Applying Liquid with Backpack, 

 Mixing/Loading/Applying Wettable Powders in Water-Soluble Packaging with Hose-end 

Sprayer, 

 Mixing/Loading/Applying Wettable Powders in Water-Soluble Packaging with 

Manually-Pressurized Hand-wand, 

 Mixing/Loading/Applying Wettable Powders in Water-Soluble Packaging with 

Backpack, 

 Applying Granules with Push-Type Rotary Spreader, 

 Applying Granules with Belly Grinder, 

 Applying Granules with Spoon, 

 Applying Granules with Cup, 

 Applying Granules with Hand Dispersal, 

 Applying Granules with Shaker Can. 

The combined dermal and inhalation MOEs for residential handlers ranged from 240 to 

21,000,000. The MOEs for all of the scenarios exceed the LOC of 100 which indicate that the 

residential handler exposure risk estimates are not of concern. The residential handler exposures 

and MOEs are calculated as detailed in Table 6.1.1.
Page 26 of 46 

Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Level of Concern Dermal Unit Exposure (mg/lb ai) Inhalation Unit Exposure (mg/lb ai) Maximum Application Rate1 Area Treated or Amount Handled Daily2 Dermal Inh

Dose (mg/kg/day)3 MOE4 Dose (mg/kg/day)5 

Mixer/Loader/Applicator 

Lawns/Turf Liquid with Hose-End Sprayer 100 13.4 0.022 0.36 lb ai/A 0.5 acres 0.027 2,200 0.000058 Lawns/Turf Liquid with Manually-Pressurized Handwand 

100 63 0.018 0.017 lb ai/gallon 5 gallons 0.06 1,000 0.000022 

Lawns/Turf Liquid with Sprinkler Can 100 13.4 0.022 0.000008 lb ai/ft 2 1,000 ft2 0.0012 50,000 0.0000026 Lawns/Turf Liquid with Backpack 100 130 0.14 0.017 lb ai/gallon 5 gallons 0.12 480 0.00017 Lawns/Turf Liquid with Backpack (Edging/Banding) 

100 130 0.14 0.034 lb ai/gallon 5 gallons 0.2482 240 0.00034 

Lawns/Turf Wettable Powders in WaterSoluble Packaging with Hose-End Sprayer 

100 6.26 0.034 0.34 lb ai/A 0.5 acres 0.012 5,000 0.000084 

Lawns/Turf Wettable Powders in WaterSoluble Packaging with Manually-Pressurized Handwand 

100 63 0.018 0.016 lb ai/gallon 5 gallons 0.057 1,100 0.000021 

Lawns/Turf Wettable Powders in WaterSoluble Packaging with Backpack 

100 63 0.018 0.016 lb ai/gallon 5 gallons 0.057 1,100 0.000021 

Lawns/Turf Granule with Push-Type Rotary Spreader 

100 0.81 0.0026 0.88 lb ai/A 0.5 acres 0.004 15,000 0.000017 

Lawns/Turf Granule with Belly Grinder 100 360 0.039 0.00002 lb ai/ft2 1,200 ft2 0.097 620 0.000014 Lawns/Turf Granule with Spoon 100 6.2 0.087 0.00002 lb ai/ft2 100 ft2 0.00014 430,000 0.0000025 Lawns/Turf Granule 100 0.11 0.013 0.00002 lb 100 ft2 0.0000025 24,000,000 0.00000038 
Page 27 of 46 

Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Level of Concern Dermal Unit Exposure (mg/lb ai) Inhalation Unit Exposure (mg/lb ai) Maximum Application Rate1 Area Treated or Amount Handled Daily2 Dermal Inh

Dose (mg/kg/day)3 MOE4 Dose (mg/kg/day)5 

with Cup ai/ft2Lawns/Turf Granule with Hand Dispersal 100 160 0.38 0.00002 lb ai/ft2 100 ft2 0.0036 17,000 0.000011 Lawns/Turf Granule with Shaker Can 100 0.11 0.013 0.00002 lb ai/ft2 100 ft2 0.0000025 24,000,000 0.00000038 

1 Based on currently registered trinexapac-ethyl labels. 2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html). 

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) × 

(77.5%) ÷ Body Weight (69 kg). 

4 Dermal MOE = Dermal NOAEL (60 mg/kg/day) ÷ Dermal Dose (mg/kg/day). 5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/d

6 Inhalation MOE = Inhalation NOAEL (60 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 7 Total MOE = NOAEL (60 mg/kg/day) ÷ (Dermal Dose + Inhalation Dose) 
Page 28 of 46 

6.2 Residential Post-application Exposure/Risk Characterization 

There is the potential for post-application exposure for individuals exposed as a result of being

an environment that has been previously treated with trinexapac-ethyl. Although there is the 

potential for dermal and oral post-application exposure to children, no dermal or oral exposure

endpoints were identified (see rationale in Section 4.0, Hazard Characterization above). 

Therefore, quantitative dermal and incidental oral post-application assessments for children w

not conducted. 

The quantitative exposure/risk assessment for residential post-application exposures is based o

the following scenarios: 

 Adults (dermal) performing high contact yard work on treated turf, 

 Adults (dermal) mowing treated turf, and 

 Adults (dermal) playing golf on treated turf. 

 Child 11 to < 16 years old (dermal) playing golf on treated turf 

 Child 11 to < 16 years old (dermal) mowing treated turf 

The residential post-application dermal MOEs ranged from 450 to 61,000 and therefore do no

exceed HED’s LOC (MOEs ≥ 100). A summary of the residential post-application 

exposures/risk estimates is presented in Table 6.2.1. 

Table 6.2.1 Residential Post-application Non-Cancer Exposure and Risk Estimates for Trinexapac-ethy

Lifestage 

Post-application Exposure 

Scenario TTR 

(ug/cm2)

1

 

Dose 

(mg/kg/day)2 MOEs3

Use Site Activity / Route 

of Exposure 

Sprays 

Child 11 to < 

16 years old Turf Golf Course 

(Dermal) 0.008 0.002 31,000 

Child 11 to 

16 years old Turf Mowing (Dermal) 0.016 0.001 61,000 

Adult Turf 

High Contact 

Lawn Activities 

(Dermal) 

0.016 0.049 1,200 

Mowing (Dermal) 0.016 0.001 61,000 

Golf Course 

(Dermal) 0.008 0.002 31,000 

Granular Formulation 

Child 11 to < 

16 years old Turf Golf Course 

(Dermal) 0.020 0.005 13,000 

Child 11 to 

16 years old Turf Mowing (Dermal) 0.040 0.002 25,000 

Adult Turf 

High Contact 

Lawn Activities 

(Dermal) 

0.040 0.135 450 

Mowing (Dermal) 0.040 0.002 24,000 
Page 29 of 46 

Table 6.2.1 Residential Post-application Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Lifestage 

Post-application Exposure 

Scenario TTR 

(ug/cm2)

1

 

Dose 

(mg/kg/day)2 MOEs3

Use Site Activity / Route 

of Exposure 

Golf Course 

(Dermal) 0.020 0.005 13,000 

1 TTR= chemical-specific data from MRID 45260201 for the Georgia site adjusted for differences in application rates (0.36 lb ai/A for 

residential turf and 0.18 lb ai/A for golf courses). 

2 Dose (mg/kg/day) equations 

3 MOE = POD (60 mg/kg/day) ÷ Dose (mg/kg/day).

6.3 Residential Risk Estimates for Use in Aggregate Assessment 

Table 6.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for trinexapac-ethyl. 

 The recommended residential exposure for use in the adult aggregate assessment reflects 

dermal and inhalation exposure from handler exposure to sprays that are applied on turf 

with backpack sprayers (edging/banding), which resulted in a MOE of 240. 

 The recommended residential exposure use in the child aggregate assessment reflects 

dermal exposure from mowing turf that has been treated with a granular formulation, 

which resulted in a MOE of 13,000. 
Page 30 of 46 

Table 6.3.1. Recommendations for the Residential Exposures for the Trinexapac-ethyl Aggregate Assessment.1

Lifestage 

Residential Handler Residential Post-application 

Dose (mg/kg/day)2 MOE3 Dose (mg/kg/day)4 

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inh

Short-Term

Adult Female 0.2482 0.00034 0.249 240 170,000 240 0.135 N/A N/A 0.135 450 Child 11 to 16 years old N/A N/A N/A N/A N/A N/A 0.005 N/A N/A 0.005 13,000 1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed from Table 5.1.1. Total = dermal + inhalation. 

3 Residential Handler MOE = the MOEs associated with the highest doses identified in Table 5.1.1. Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE). 4 Residential Post-application Dose = the highest post-application dose for each applicable lifestage of all scenarios assessed from Table 5.2.1. Total = dermal + inhalat

applicable. 

5 Residential Post-application MOE = the MOEs associated with the highest doses identified in Table 5.2.1. Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/In
Page 31 of 46

6.4 Spray Drift 

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling coupled with methods 

employed for residential risk assessments for turf products. 

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.2

 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

Several trinexapac-ethyl products have existing labels for use on turf, thus it was considered 

whether the risk assessment for that use may be considered protective of any type of exposure 

that would be associated with spray drift. It should be noted that the registered residential uses 

on turf result in exposure greater than potential exposure from spray drift; therefore, no new 

residential assessment for spray drift needs to be completed. If the maximum application rate on 

crops adjusted by the amount of drift expected is less than or equal to existing turf application 

rates, the existing turf assessment is considered protective of spray drift exposure. The proposed 

maximum single application rate of trinexapac-ethyl on grasses grown for seed is 0.5 lb ai/acre. 

According to the Tier 1 output from the groundboom spray profile of the AgDrift model, 

trinexapac-ethyl passed the spray drift screening because the maximum application rate to a crop 

target site (grasses grown for seed) multiplied by the adjustment factor for drift of 0.26 is less 

than the direct spray residential turf application rate (0.36 lb ai/A)3

. The turf post-application 

MOEs have been previously assessed and are based on the revised SOPs for Residential 

Exposure Assessment (see above in Section 6.2). 

6.5 Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for trinexapac-ethyl at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category III and IV). However, volatilization of pesticides 

may be a source of post-application inhalation exposure to individuals nearby pesticide 

applications. The Agency sought expert advice and input on issues related to volatilization of 

 

2 This approach is consistent with the requirements of the EPA’s Worker Protection Standard and the language

proposed in the PR Notice 2009 which, when included on all labels, precludes direct exposure pathways. 3 0.5 lb ai/A x 0.26 = 0.13 lb ai/A
Page 32 of 46

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 20104

. The Agency is 

in the process of evaluating the SAP report and may, as appropriate, develop policies and 

procedures to identify the need for and, subsequently, the way to incorporate post-application 

inhalation exposure into the Agency's risk assessments. If new policies or procedures are 

developed, the Agency may revisit the need for a quantitative post-application inhalation 

exposure assessment for trinexapac-ethyl. 

7.0 Aggregate Exposure/Risk Characterization 

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. 

7.1 Acute Aggregate Risk

Acute aggregate risk results from exposure to residues in food and drinking water alone. The 

acute dietary exposure analysis included both food and drinking water. Therefore, acute 

aggregate risk is equivalent to the acute dietary risk, as discussed in Section 5.2.3, above. All 

risk estimates are below HED’s level of concern. 

7.2 Short- and Intermediate-Term Aggregate Risk 

The short- and intermediate-term toxicological endpoints for trinexapac-ethyl are the same for 

each route of exposure. Therefore, for residential exposure scenarios, only short-term exposures 

were assessed, and are considered to be protective of intermediate-term exposure and risk. 

Exposures from these scenarios are aggregated with chronic dietary exposure from food and 

water which is considered to be background exposure. The LOC for these exposure routes are 

all 100. 

For the adult short- and intermediate-term aggregate risk assessment, chronic dietary exposure 

was added directly to the adult and children 11- 16 years old post-application exposure estimate. 

To be health protective, the post-application scenario was used in the aggregate because it 

resulted in higher exposure than the handler scenario. The chronic dietary exposure estimate for 

females 13-49 years old and youth 13-19 years old were used to determine the aggregate risk 

estimate. 

Short-term aggregate margins of exposure for adult and children exceed HED’s level of concern 

of 100 and are not of concern (MOEs > 100). Short and intermediate estimated exposure and 

risks are shown below in Table 7.2.a. 

 

4 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 33 of 46

Table 7.2.a Short-Term and/or Intermediate Term Dermal Aggregate Risk Calculations 

Short- or Intermediate-Term Scenario

Population NOAEL 

mg/kg/day

LOC1 Max 

Allowable 

Exposure 

mg/kg/day2

Average 

Food and 

Water 

Exposure 

mg/kg/day3

Residential 

Postapplication 

Dermal 

Exposure 

mg/kg/day4 

Total 

Exposure 

mg/kg/day5 

Aggregate 

MOE (food, 

water, and 

residential)6 

Sprays 

Child 11- 16 

yrs old 60 100 0.60 

0.007701 0.002 0.009701 6,200 

Adult 

Female 0.005741 0.049 0.054741 1,100 

Granular Formulation 

Child 11- 16 

yrs old 60 100 0.60 

0.007701 0.005 0.012701 4,700 

Adult 

Female 0.005741 0.135 0.140741 430 

1

 An UF of 100x was applied to account for interspecies extrapolation (10x) and intraspecies variation 

(10x) and no additional uncertainty factors/safety factors are required. 

2

 Maximum Allowable Exposure (mg/kg/day) = NOAEL/ (60 mg/kg/day)/LOC (100) 

3 Average food and water exposure from chronic dietary exposure for youth 13-19 yrs old and females 13-

49 yrs old. See Table 5.2.6 

4

Residential Exposure = Dermal exposure from treated turf (see table 6.2.1). 

5

 Total Exposure = Avg Food & Water Exposure + Residential Exposure 

6

 Aggregate MOE = [NOAEL / (Avg Food & Water Exposure + Residential Exposure)] 

7.3 Cancer Aggregate Risk

The CARC classified trinexapac-ethyl as “not likely to be carcinogenic to humans.” The chronic 

dietary risk assessment is protective of cancer effects and, therefore, cancer risk resulting from 

exposure to trinexapac-ethyl is not of concern. 

8.0 Cumulative Exposure/Risk Characterization

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. The Agency determined that there was 

insufficient evidence to suggest trinexapac-ethyl shares a common mechanism of toxicity with 

other chemical substances. For information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see the policy statements released by EPA’s Office of Pesticide Program concerning 

common mechanism determinations and procedures for cumulating effects from substances 
Page 34 of 46

found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/. 

9.0 Occupational Exposure/Risk Pathway

9.1 Occupational Handler Exposure/Risk Estimates 

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the currently 

registered uses. The quantitative exposure/risk assessment developed for occupational handlers 

is based on the following scenarios: 

 Mixing/Loading Granules for Tractor Drawn Spreader Applications 

 Mixing/Loading Liquids for Aerial Applications 

 Mixing/Loading Liquids for Chemigation 

 Mixing/Loading Liquids for Groundboom Applications 

 Mixing/Loading Wettable Powders in Water Soluble Bags for Aerial Applications 

 Mixing/Loading Wettable Powders in Water Soluble Bags for Chemigation 

 Mixing/Loading Wettable Powders in Water Soluble Bags for Groundboom Applications 

 Applying Sprays for Aerial Applications 

 Applying Sprays for Groundboom Applications 

 Applying Granules for Tractor Drawn Spreader Applications 

 Flagging (Sprays) during Aerial Applications 

 Mixing/Loading/Applying Liquids for Backpack Applications 

 Mixing/Loading/Applying Liquids for Manually-Pressurized Handwand Applications 

 Mixing/Loading/Applying Liquids for Mechanically-Pressurized Handgun Applications 

 Mixing/Loading/Applying Wettable Powders in Water Soluble Bags for Backpack 

Applications 

 Mixing/Loading/Applying Wettable Powders in Water Soluble Bags for ManuallyPressurized Handwand Applications 

 Mixing/Loading/Applying Wettable Powders in Water Soluble Bags for MechanicallyPressurized Handgun Applications 

 Loading/Applying Granules for Belly Grinder Applications 

 Loading/applying granules for Rotary Spreader Applications 

The short- and intermediate-term risk estimates for occupational handlers are included in Table 

9.1.1. All dermal and inhalation occupational handler scenarios are above HED’s LOC (MOEs 

≥ 100) with baseline attire and/or gloves and engineering control (i.e., enclosed cockpits) for 
Page 35 of 46

aerial applications. With baseline attire and/or gloves, the dermal plus inhalation MOEs range 

from 140 to 2,100,000.
Page 36 of 46

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Crop or Target 

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inh

Mitigation Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day

Mixing/Loading Granules 

Tractor-Drawn Spreader 

Application 

Golf Course 

(Fairways, 

Tees, Greens) 

8.4 1.7 0.44 40 0.00166 36,000 0.000433 

Golf Course 

(Tees and 

Greens Only) 

8.4 1.7 0.44 5 0.000208 290,000 0.0000542 

Mixing/Loading Liquids 

Aerial Application 

Sod 220 0.219 0.36 350 0.314 190 0.000404 

Grasses Grown 

For Seed 220 0.219 0.5 350 0.432 140 0.000555 

Sugarcane 220 0.219 0.31 350 0.268 220 0.000345 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

220 0.219 0.11 1200 0.326 180 0.000419 

Chemigation Application 

Sod 220 0.219 0.36 350 0.314 190 0.000404 

Grasses Grown 

For Seed 220 0.219 0.5 350 0.432 140 0.000555 

Sugarcane 220 0.219 0.31 350 0.268 220 0.000345 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

220 0.219 0.11 350 0.0951 630 0.000122 

Groundboom Application 

Golf Course 

(Tees and 

Greens Only) 

220 0.219 0.07 5 0.000865 69,000 0.0000011

Golf Course 

(Fairways, 

Tees, Greens) 

220 0.219 0.18 40 0.018 3,300 0.000023 

Sod 220 0.219 0.36 80 0.072 830 0.0000925 

Grasses Grown 

For Seed 220 0.219 0.5 80 0.0988 610 0.000127 
Page 37 of 46

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Crop or Target 

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inh

Mitigation Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day

Sugarcane 220 0.219 0.31 80 0.0613 980 0.0000787 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

220 0.219 0.11 200 0.0544 1,100 0.0000699 

Mixing/Loading Wettable Powders In Water Soluble Packaging 

Aerial Application Sod 9.8 (EC) 0.24 (EC) 0.34 350 0.0131 (EC) 4,600 (EC) 0.000414 (E

Chemigation Application Sod 9.8 (EC) 0.24 (EC) 0.34 350 0.0131 (EC) 4,600 (EC) 0.000414 (E

Groundboom 

Golf Course 

(Tees and 

Greens Only) 

9.8 (EC) 0.24 (EC) 0.05 5 0.0000275 (EC) 2,200,000 (EC) 0.0000008

(EC) 

Groundboom 

Golf Course 

(Fairways, 

Tees, Greens) 

9.8 (EC) 0.24 (EC) 0.17 40 0.000748 (EC) 80,000 (EC) 0.0000236 (EC) 

Groundboom Sod 9.8 (EC) 0.24 (EC) 0.34 80 0.003 (EC) 20,000 (EC) 0.0000946 (EC) 

Appling Sprays 

Aerial Application 

Sod 2.08 (EC) 0.0049 (EC) 0.36 350 0.00298 (EC) 20,000 (EC) 0.0000090

(EC) 

Grasses Grown 

For Seed 2.08 (EC) 0.0049 (EC) 0.5 350 0.00409 (EC) 15,000 (EC) 0.0000124(E

Sugarcane 2.08 (EC) 0.0049 (EC) 0.31 350 0.00254 (EC) 24,000 (EC) 0.0000077

(EC) 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

2.08 (EC) 0.0049 (EC) 0.11 1200 0.00309 (EC) 19,000 (EC) 0.0000093

(EC) 

Groundboom Application 

Golf Course 

(Tees and 

Greens Only) 

78.6 0.34 0.07 5 0.000309 190,000 0.0000017

Golf Course 

(Fairways, 

Tees, Greens) 

78.6 0.34 0.18 40 0.00642 9,300 0.0000359 
Page 38 of 46

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Crop or Target 

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inh

Mitigation Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day

Sod 78.6 0.34 0.36 80 0.0257 2,300 0.000143 

Grasses Grown 

For Seed 78.6 0.34 0.5 80 0.0353 1,700 0.000197 

Sugarcane 78.6 0.34 0.31 80 0.0219 2,700 0.000122 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

78.6 0.34 0.11 200 0.0194 3,100 0.000108 

Applying Granules 

Tractor-Drawn Spreader 

Application 

Golf Course 

(Fairways, 

Tees, Greens) 

9.9 1.2 0.44 40 0.00195 31,000 0.000306 

Tractor-Drawn Spreader 

Application 

Golf Course 

(Tees and 

Greens Only) 

9.9 1.2 0.44 5 0.000245 240,000 0.0000383 

Flagger 

Aerial Application 

Sod 11 0.35 0.36 350 0.0157 3,800 0.000646 

Grasses Grown 

For Seed 11 0.35 0.5 350 0.0217 2,800 0.000888 

Sugarcane 11 0.35 0.31 350 0.0134 4,500 0.000551 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

11 0.35 0.11 350 0.00476 13,000 0.000196 

Mixing/Loading/Appling Liquids 

Backpack Application 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

8260 2.58 0.017 40 0.0631 950 0.0000254 

Manually –Pressurized 

Handwand 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

100000 

(baseline) 30 0.017 40 

0.764 

(baseline) 

79 

(baseline) 0.000296 

430 

(with gloves) 

0.00328 

(with gloves)

18,000 

(with 
Page 39 of 46

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Crop or Target 

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inh

Mitigation Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day

gloves) 

Backpack Application 

Edging/Banding 

for Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

8260 2.58 0.03 40 0.11 540 0.0000449 

Manually –Pressurized 

Handwand 

Edging/Banding 

for Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

100000 

(baseline) 

30 0.03 40 

1.35 

(baseline) 

44 

(baseline)

0.000522 

430 

(with gloves) 

0.0058 

(with gloves)

10,000 

(with 

gloves) 

Mechanically-Pressurized 

Handgun 

Golf Course 

(Tees and 

Greens Only) 

1140 1.9 0.07 5 0.00448 13,000 0.0000096

Mechanically-Pressurized 

Handgun 

Golf Course 

(Fairways, 

Tees, Greens) 

1140 1.9 0.18 5 0.0117 5,100 0.0000251 

Mechanically-Pressurized 

Handgun 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

1140 1.9 0.36 5 0.0233 2,600 0.0000501 

Mechanically-Pressurized 

Handgun 

Edging/Banding 

for Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

1140 1.9 0.73 5 0.0467 1,300 0.000101 

Mixing/Loading/Applying Wettable Powders In Water Soluble Packaging

Backpack Application 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

8260 2.58 0.016 40 0.0594 1,000 0.0000239 

Manually –Pressurized 

Handwand 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

100000 

(baseline) 30 0.016 40 

0.719 

(baseline) 

83 

(baseline) 0.000278 

430 0.00309 19,000 
Page 40 of 46

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Crop or Target 

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inh

Mitigation Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day

Parks, etc.) (with gloves) (with gloves) (with 

gloves) 

Backpack Application 

Edging/Banding 

for Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

8260 2.58 0.03 40 0.11 540 0.0000449 

Manually –Pressurized 

Handwand 

Edging/Banding 

for Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

100000 

30 0.03 40 

1.35 

(baseline) 

44 

(baseline)

0.000522 

430 

(with gloves) 

0.0058 

(with gloves)

10,000 

(with 

gloves) 

Mechanically-Pressurized 

Handgun 

Golf Course 

(Tees and 

Greens Only) 

1350 18 0.05 5 0.0038 16,000 0.0000652 

Mechanically-Pressurized 

Handgun 

Golf Course 

(Fairways, 

Tees, Greens) 

1350 18 0.17 5 0.0129 4,700 0.000222 

Mechanically-Pressurized 

Handgun 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

1350 18 0.34 5 0.0258 2,300 0.000443 

Mechanically-Pressurized 

Handgun 

Edging/Banding 

for Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

1350 18 0.68 5 0.0516 1,200 0.000887 

Loading/Applying Granules 

Belly Grinder Application 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

10000 62 0.88 1 0.0988 610 0.000791 

Rotary Spreader 

Application 

Golf Course 

(Tees and 440 10 0.44 5 0.0109 5,500 0.000319 
Page 41 of 46

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Trinexapac-ethyl. 

Exposure Scenario Crop or Target 

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inh

Mitigation Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day

Greens Only) 

Rotary Spreader 

Application 

Golf Course 

(Fairways, 

Tees, Greens) 

440 10 0.44 5 0.0109 5,500 0.000319 

Rotary Spreader 

Application 

Landscaping 

Turf (Lawns, 

Athletic Fields, 

Parks, etc.) 

440 10 0.88 5 0.0218 2,800 0.000638 

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Baseline (single layer of clothing, no gl

with gloves, or Eng. Controls (EC; closed cockpit) for aerial applicators. 

2 Based on currently registered labels. 

3 Exposure Science Advisory Council Policy #9.1. 4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or g

(69 kg). 

5 Dermal MOE = Dermal NOAEL (60 mg/kg/day) ÷ Dermal Dose (mg/kg/day). 6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A 

7 Inhalation MOE = Inhalation NOAEL (60 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 

8 Total MOE = NOAEL (60 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.
Page 42 of 46 

9.2 Occupational Post-application Exposure/Risk Estimates 

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure. 

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates 

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for trinexapac-ethyl at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category III and IV). However, there are multiple potential 

sources of post-application inhalation exposure to individuals performing post-application 

activities in previously treated fields. These potential sources include volatilization of pesticides 

and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 

received the SAP’s final report on March 2, 20105

. The Agency is in the process of evaluating 

the SAP report as well as available post-application inhalation exposure data generated by the 

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, 

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

Agency's risk assessments. If new policies or procedures are put into place, the Agency may 

revisit the need for a quantitative occupational post-application inhalation exposure assessment 

for trinexapac-ethyl.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios. 

 

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates 

A series of assumptions and exposure factors served as the basis for completing the occupational 

post-application risk assessments. Each assumption and factor is detailed in Table 9.2.2.1 below 

on an individual basis.

 

5 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 43 of 46 

Table 9.2.2.1. Anticipated Post-Application Activities and Dermal Transfer Coefficients. 

Crops 

Policy Crop 

Group 

Category 

Crop 

Height 

Foliage 

Density 

Transfer 

Coefficients 

(cm2/hr)

Activities 

Golf Course Turf/sod Low Full 3700 Maintenance 

Golf Course Turf/Sod Low Full 2500 Maintenance, greens only 

Sod Turf/Sod Low Full 6700 Maintenance, Slab Harvesting, 

Transplanting/Planting 

Sugarcane Sugarcane High Full 1100 Scouting 

Sugarcane Sugarcane High Full 8800 Hand Harvesting 

Sugarcane Sugarcane Low Minimum 70 Hand Weeding 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

Field/row 

crop, 

low/medium 

Low Full/Minimum 1100 Scouting 

Cereals (Wheat, 

Barley, Oats, 

Triticale) 

Field/row 

crop, 

low/medium 

Low Full/Minimum 70 Hand Weeding 

Grasses Grown For 

Seed 

Field/row 

crop, 

low/medium 

Low Full 1900 Hand Set Irrigation 

Grasses Grown For 

Seed 

Field/row 

crop, 

low/medium 

Low Minimum 1100 Scouting 

Dislodgeable Foliar Residues 

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are 

required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 

Standard Operating Procedures for Residential Pesticide Exposure Assessment, HED analyzed a 

number of DFR studies and selected a new default value for the fraction of the application rate 

available to be dislodged after a foliar application (FAR). This default value is 25% and is based 

on an analysis of 19 DFR studies where the FAR value ranged from 2% to 89%. This value is 

recommended for use in both residential and occupational post-application assessments. Of the 

analyzed DFR studies, the maximum FAR value seen was 89% or 3.6 times higher than the 

default residue transfer value. Therefore, the HED has decided that a calculated MOE of 

approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 100) 

using the default dislodged residue values would provide an adequate margin of safety for any 

potentially higher residues seen in a chemical-specific DFR study (Guidance for 

Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) 

Studies. 6/7/2012, Exposure Science Advisory Council). A DFR study will be required for 
Page 44 of 46 

future assessments since there are dermal MOEs less than 4 times the LOC based on default 

values for the fraction of application rate available for transfer after a foliar application. 

Chemical-specific TTR data are available for trinexapac-ethyl and were used in the occupational 

post-application exposure assessment to assess turf in conjunction with standard default 

assumptions to assess sugarcane, cereals (wheat, barley, oats, triticale), and grasses grown for 

seed. Therefore, the assessment uses surface residues from the day of application (assume that 

individuals could be exposed to residues immediately after application) for occupational turf 

uses.

The short- and intermediate-term occupational post-application dermal exposure and risk 

estimates indicate that the MOEs are not of concern to HED (i.e., MOEs ≥ 100) on the day of 

application, except for hand-harvesting sugarcane (MOE=87) where risk estimates are of concern 

until 2 days after application (MOE=110) as detailed in Table 9.2.2.2. 

Table 9.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Trinexapacethyl.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Short-term/Intermediate-term 

Granular Formulation 

Golf Course (Turf/Sod) Maintenance 3700 0.015 0.005 12,000 

Golf Course (Turf/Sod) Maintenance, Greens 

Only 2500 0.015 0.003 18,000 

Liquid Formulations 

Golf Course (Turf/Sod) Maintenance 3700 0.006 0.002 29,000 

Golf Course (Turf/Sod) Maintenance, Greens 

Only 2500 0.006 0.001 43,000 

Sod (Turf/Sod) 

Maintenance, 

Harvesting, Slab, 

Transplanting 

6700 0.012 0.008 8,000 

Sugarcane Scouting 1100 0.87 0.086 700 

Sugarcane Hand Harvesting 8800 0.87 0.688 

87 (MOE=110 at 

Day 2 after 

treatment) 

Sugarcane Hand Weeding 70 0.87 0.005 11,000 

Cereals (Wheat, Barley, 

Oats, Triticale) Scouting 1100 0.31 0.030 2,000 

Cereals (Wheat, Barley, 

Oats, Triticale) Hand Weeding 70 0.31 0.002 31,000 

Grasses Grown For 

Seed Hand Set Irrigation 1900 1.40 0.239 250 

Grasses Grown For 

Seed Scouting 1100 1.40 0.139 430 

1 DFR = Application Rate × F × (1-D)t× 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day or TTR = chemical-specific 

data from MRID 45260201 for the Indiana site adjusted for differences in application rates 

2 Daily Dermal Dose = [DFR (μg/cm2

) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (77.5%)]  BW (69 kg).

3 MOE = POD (60 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm2

) × TC × 0.001 mg/μg × 8 hrs/day × dermal 

absorption factor (77.5%)]  BW (69 kg).
Page 45 of 46 

Restricted Entry Interval

The REI specified on the currently registered labels is based on the acute toxicity of trinexapac 

ethyl. Trinexapac-ethyl is classified as Toxicity Category III via the dermal route and Toxicity 

Category IV for skin irritation potential. It is not a skin sensitizer. Short- and intermediate-term 

post-application risk estimates were not a concern on day 0 (12 hours following application) for 

all post-application activities. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute III or 

IV for acute dermal, eye irritation and primary skin irrigation are assigned a 12-hour REI. 

Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate 

to protect agricultural workers from post-application exposures to trinexapac-ethyl. 

10.0 References

DP#: 377921 

Subject: Trinexapac-ethyl: Human Health Risk Assessment for the Section 3 Registration 

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

From: S. Piper, J. Facey, and M. Hawkins 

To: B. Benbow and K. Montague 

Date: 11/23/11 

MRIDs: NA 

DP#: 409833 

Subject: Trinexapac-ethy Drinking Water Assessment to Support Registration Review. 

From: C. Koper 

To: A. Jakob, C. Olinger, and S. Piper 

Date: 03/11/13 

MRIDs: NA 

DP#: 413986 

Subject: Trinexapac-ethyl : Acute and Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessments to Support Registration Review

From: S. Piper 

To: K. Keller 

Date: 09/12/2013 

MRIDs: NA 

DP#: 463873 

Subject: Trinexapac-ethyl. Preliminary Occupational and Residential Exposure/Risk 

Assessment for Registration Review

From: M. Hawkins 

To: S. Piper and K. Keller 

Date: 08/01/13 

MRIDs: NA 
Page 46 of 46 

DP#: 392798 

Subject: Trinexapac-ethyl: Occupational and Residential Exposure/Risk Assessment for 

Proposed Uses on grasses grown for seed, sugarcane, and cereals (wheat, barley, 

and oats).

From: M. Hawkins 

To: M. Waller and T. Stowe 

Date: 08/31/11 

MRIDs: NA