Trifluralin Human Health Risk Assessment DP No. D401005 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

:MEMORANDUM 

DATE: Apri12, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Trifluralin: Human Health Risk Assessment for the Establishment of Tolerances 

on Oilseed Crop Group 20. 

PC Code: 036101 

Decision No.: 463234 

Petition No.: NA 

Risk Assessment Type: Single 

Chemical/ Aggregate 

DP Barcode: 0401005 

Registration No.: NA 

Regulatory Action: Section 3 Registration 

Reregistration Case No.: NA 

TXR No.: NA CAS No.: 1582-09-8 

MRID No.: NA 40 CFR: 180.207 

REVIEWER: Sheila 

Nancy 

Piper

McCarroll, 

, Chemist/Risk 

Toxicologist 

Assessor .0~ (}l~ 

Shalu Shelat, Industrial Hygienist/ORE Assessor 

Risk Assessment Branch VI 

Health Effects Division (7509P) A 

THROUGH: Felecia Fort, Branch Chief .-C kc.tO.:jcJL -tRisk Assessment Branch VI dJ 

Health Effects Division (7509P) 

TO: Andrew Ertman, Review Manager Reviewer 

Barbara Madden, Risk Manager 

Registration Division (7505C) 

Page 1 of 56 
Trifluralin Human Health Risk Assessment DP No. D401005 

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

2.0 HED Recommendations ..................................................................................................... 5 

2.1 Data Deficiencies ................................ ................................................. ..................... .......... 5 

2.2 Tolerance Considerations ................................................. ................................................ 5 

2.2.1 Enforcement Analytical Method ...................................................................................... 5 

2.2.2 Recommended Tolerances ................................................................................................ 5 

2.2.3 Revisions to Petitioned-For Tolerances ........................................................................... 6 

2.2.4 International Harmonization ............................................................................................ 6 

2.3 Label Recommendations ................................................................................................... 6 

2.3.1 Recommendations from Residue Reviews .......................... ...................................... ....... 6 

2.3.2 Recommendations from Occupational Assessment.. ...................................................... 6 

2.3.3 Recommendations from Residential Assessment.. .......................................................... 6 

3.0 Introduction .............................. ............... .................. .... ...................................................... 6 

3.1 Chemical Identity ........................................................................................................... .... ? 

3.2 PhysicaVChemical Characteristics ................................................................................... 7 

3.3 Pesticide Use Pattern ......................................................................................................... 8 

3.4 Anticipated Exposure Pathways ..................................................................................... 10 

3.5 Consideration of Environmental Justice ....................................................................... 10 

4.0 Hazard Characterization and Dose-Response Assessment.. ......................................... 10 

4.2.1 Completeness of the Toxicology Database ................... .................................................. 12 

5.1 Residues of Concern Summary and Rationale ............................................................. 16 

5.2 Food Residue Profile .. ...................................................................................................... 17 

5.3 Water Residue Profile ..................................................................................................... 17 

5.4 Dietary Risk Assessment ................................................................................................. 19 

5.4.1 Description of Residue Data Used in Dietary Assessment ........................................... 19 

5.4.2 Percent Crop Treated Used in Dietary Assessment ...................................... ................ 19 

5.4.3 Acute Dietary Risk Assessment ......................................................... ........ ..................... 19 

5.4.4 Chronic Dietary Risk Assessment .................................................................................. 19 

5.4.5 Cancer Dietary Risk Assessment.. .................................................................................. 20 

5.4.6 Summary Table ................................................................................................................ 20 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .............................. 20 

6.1 Residential Handler Exposure ........................................................................................ 21 

6.2 Post-Application Exposure ............................................................................................. 25 

6.4 Residential Risk Estimates for Use in Aggregate Assessment.. ................................... 29 

6.5 Residential Bystander Post-application Inhalation Exposure ................ ..................... 31 

6.6 Spray Drift ....................................................... ................................................................. 31 

7.0 Aggregate Exposure/Risk Characterization ................................................................... 31 

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

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

7.3 Cancer Aggregate Risk ......................................................... ........................................... 32 

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

9.0 Occupational Exposure/Risk Characterization ............................................................. 33 

10.0 References .......................................................................................................................... 33 

Appendix A. Toxicology Profile and Executive Summaries .................................................. .41 

A. I Toxicology Data Requirements ................................................................. ..................... 41 

A.2 Toxicity Profiles ............................................................ ................................................... 43 

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Trifluralin Human Health Risk Assessment DP No. D401005

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Executive Summary

The Interregional Research Project No. 4 (IR-4), on behalf of the states of DE and MT has 

proposed, in PP#2E8011, the establishment of permanent tolerances for residues of the herbicide, 

trifluralin, in/on Oilseed crop group 20. This request is a conversion of existing Rapeseed 

subgroup 20A, Sunflower subgroup 20B, and Cottonseed subgroup 20C tolerances to the Oilseed 

crop group 20 tolerance.

Trifluralin (2, 6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine) is a selective, preemergence, dinitroaniline herbicide registered for the control of annual grasses and certain 

broadleaf weeds. Trifluralin is registered for use on a variety of food and feed crops, and in 

residential settings, including turf, ornamentals, and vegetable gardens. The petitioner, IR-4, is 

proposing the following tolerances on the food commodities as shown below:

Commodity Proposed Tolerance (ppm) Comment (correct commodity 

definition)

Cotton, undelinted seed 0.05 Remove cotton, flax, mustard, 

rapeseed, safflower and 

sunflower seed to Oilseed 

Crop group 20

Flax, seed 0.05

Mustard, seed 0.05

Rapeseed, seed 0.05

Safflower, seed 0.05

Sunflower, seed 0.05

The toxicity database for trifluralin is substantially complete. An immunotoxicity study is 

required for registration review under the new data requirements for pesticides (40 CFR § 158). 

Following data evaluation, HED will determine if this study will impact the toxicity endpoints 

for trifluralin. As part of the registration review risk assessment process, the need for the 

required neurotoxicity battery (acute and subchronic neurotoxicity studies) was discussed by the 

Hazard and Science Policy Council (HASPOC) on March 15, 2012. The available data on 

trifluralin and other structurally related dinitroanilines did not indicate a concern for 

neurotoxicity. The HASPOC concluded that based on a weight-of-evidence approach, 

considering all the available hazard and exposure information for trifluralin, the acute and 

subchronic neurotoxicity studies are not needed at this time. The requirement for the 

immunotoxicity study remains outstanding.

Trifluralin exhibits low acute toxicity in rats via the oral, dermal, and inhalation routes of 

exposure. In the rabbit studies, trifluralin has an LD50 value of 5000 mg/kg when applied 

dermally (Toxicity Category IV). It is a slight eye irritant, but not a skin irritant; however, it was 

found to be a dermal sensitizer in guinea pigs. The kidney is the principal target organ. 

However, subchronic oral studies in the rat and dog show that the liver is also a target organ with 

increased liver weights and changes in clinical chemistry parameters. The Agency classified 

trifluralin as a Group C- “possible” human carcinogen. The Q1

*

of 5.79 x 10-3(mg/kg/day)-1 was 

updated to 2.96 x 10-3(mg/kg/day)-1in 2004 based on the Fischer 344 Rat Dietary 3⁄4’s scaling 

factor (May 11, 2004, TXR No. 0052534). Trifluralin is not mutagenic in a comprehensive 

battery of Genetic Toxicology studies and does not inhibit the polymerization of microtubules in 
Trifluralin Human Health Risk Assessment DP No. D401005

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mammalian cells. There is no concern for quantitative pre- and/or post-natal toxicity; the FQPA 

SF was reduced to 1x. 

Trifluralin is among the group of 58 pesticide active ingredients on the initial list to be screened 

under the Endocrine Disruptor Screening Program (EDSP). Once all required Tier 1 and Tier 2 

data have been received and reviewed, the endpoints and safety factors used for risk assessment 

purposes will be examined and a new risk assessment performed if necessary. For further 

information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, 

future lists, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

The existing residue chemistry database for trifluralin is adequate for risk assessment purposes. 

The qualitative nature of the residue in plants and animals has been adequately identified, 

characterized and is understood. The residue of concern in plants and rotational crops is the 

parent compound only. No additional data are required at this time; however, there are some 

data that have been submitted by the registrant as a result of data call-in (DCIs) requests for 

trifluralin which were outlined in the most recent residue chemistry chapter (R. Griffin, 

D296627, 03/04/04) that will be reviewed during the registration review process. 

A highly conservative acute dietary assessment using tolerance level residues, assuming 100% 

crop treated demonstrated that estimated risks were less than 1% of the acute population adjusted 

dose (aPAD) at the 95th percentile of exposure for females 13-49 years old. There were no 

appropriate toxicological effects attributable to a single exposure (dose) for the general 

population or any other population subgroups except females 13-49 years old; therefore, these 

population subgroups were not included in this assessment. The chronic and cancer dietary 

assessments were somewhat refined assuming tolerance level residues, percent crop treated data, 

and Pesticide Data Program (PDP) monitoring data on commodities which had significant impact 

on the cancer exposure. The chronic dietary exposure estimates were less than 1% of the chronic 

population adjusted dose (cPAD) for all population subgroups. The cancer dietary exposure 

estimate for the U.S. population is 2.1 x 10-7. 

There are no proposed residential uses at this time; however, there are existing residential uses 

that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs

along with policy changes for body weight assumptions. The revision of residential exposures 

will impact the human health aggregate risk assessment for trifluralin. For this assessment, HED 

considered all the uses that were presented in the 2004 TRED document (D296625. S. Recore, 

Residential Exposure Assessment and Recommendations for the Tolerance Reassessment 

Evaluation Decision (TRED) Document for Trifluralin. May 6, 2004). Trifluralin can be 

purchased and used by homeowners in residential settings. HED assumes that only short-term 

exposures are applicable to residential handler risk assessments, and are considered to be 

protective of intermediate-term exposure and risk. The short-term non-cancer exposure was 

assessed for adults and children. Residential handler inhalation risk estimates (MOEs) did not 

exceed HED’s the level of concern (i.e., MOEs >100). An adult cancer exposure and risk 

assessment was also conducted. The handler and post-application cancer risk estimates for 

adults ranged from 4 x 10-11 to 2 x 10-6.
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To estimate short-term aggregate risk, HED combined the chronic dietary (food + water) 

exposures (as a measure of average dietary exposure) with the short-term residential postapplication exposure. All short-term exposures resulted in MOEs greater than 100 for all 

populations and are not of concern to HED. Aggregate cancer risk estimates (1 x 10-6) from 

trifluralin residues in food and drinking water are below HED’s level of concern for the general 

U.S. population.

An occupational exposure and risk assessment was not conducted at this time, since this request 

is for a conversion of existing tolerance to a crop group tolerance.

2.0 HED Recommendations

Provided the registrant submits a revised Section F (see Table 2.2.2), there are no human health 

risks of concern that would preclude the establishment or revision of tolerances for the residue of 

trifluralin under 40 CFR 180.207 as follows:

Oilseed Group 20.....................0.05 ppm

2.1 Data Deficiencies

TOXICOLOGY

An immunotoxicity study is required under the new data requirements for pesticides (40 CFR 

§158).

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate enforcement method is available for trifluralin, Methods GRM96.12 and 

GRM96.13, which utilizes gas chromatography (GC) with electron capture detection (ECD). 

The reported limit of quantitation (LOQ) is 0.01 ppm. Also, trifluralin was evaluated using the 

FDA multiresidue method and the method is suitable for determining residues of trifluralin in 

plant commodities.

2.2.2 Recommended Tolerances

Tolerances should be established for residues of the dinitroaniline herbicide trifluralin, including 

its metabolite and degradate, in or on the commodities listed below. For plant and livestock

commodities, the tolerances should be established as follows: 

Tolerances are established for residues of trifluralin, 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 only trifluralin α,α,α-trifluoro-2,6-dinitroN,N-dipropyl-p-toluidine, in or on the commodity. 
Trifluralin Human Health Risk Assessment DP No. D401005

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Table 2.2.2. Proposed Tolerance

Commodity Proposed Tolerance (ppm) Comment (correct commodity 

definition)

Cotton, undelinted seed 0.05 Remove cotton, flax, mustard, 

rapeseed, safflower and 

sunflower seed to Oilseed 

Crop group 20

Flax, seed 0.05

Mustard, seed 0.05

Rapeseed, seed 0.05

Safflower, seed 0.05

Sunflower, seed 0.05

2.2.3 Revisions to Petitioned-For Tolerances

As noted in Table 2.2.2 above, the request for the conversion of the canola/rapeseed, sunflower 

seed and cottonseed tolerances to the oilseed crop 20 tolerances will remain the same. 

2.2.4 International Harmonization

There are Maximum Residue Limits (MRLs) established by Canada, but not with Codex. 

Mexico adopts US tolerances for its export purposes. Canada’s MRLs are harmonized with the 

established U.S. tolerances.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

There are no label recommendations needed as part of residue chemistry action.

2.3.2 Recommendations from Occupational Assessment

 

There are no proposed occupational uses as part of this action.

2.3.3 Recommendations from Residential Assessment

At this time there are no label recommendations from the updated residential exposure and risk 

assessment. 

3.0 Introduction
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3.1 Chemical Identity

Table 3.1 Test Compound Nomenclature

Chemical Structure

Common Name Trifluralin

Company experimental name

IUPAC name α,α,α-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine

CAS Name 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine

CAS Registry Number 1582-09-8

End-use product/EP Treflan® 5G, Treflan® E.C., Trifluralin® 4EC

3.2 Physical/Chemical Characteristics

Trifluralin has low water solubility and is strongly bound to soil components. Trifluralin is 

almost insoluble in water, with a solubility of 0.2 to 0.4 mg/L at 25°C. It is somewhat volatile, 

and has a moderately high log octanol-water partition coefficient. The full complement of 

physiochemical properties for this active ingredient is shown in Table 3.2. 

Table 3.2 Physicochemical Properties 

Parameter Value Reference

Melting point/range 42-49 C

pH 5.9 ± 0.1 saturated aqueous solution D207577, 4/9/97, K. Dockter

Density or specific gravity (22 C) 1.36 g/mL

Water solubility (25 C) <1 ppm

Solvent solubility (25 C) readily soluble in organic solvents such 

as acetone, acetonitrile, chloroform, 

dichloromethane, ethyl acetate, and 

toluene at >100 g/100 mL, and in 

hexane at 5-6.7 g/100 mL or 

methanol at 3.3-4 g/100 mL

Vapor pressure (25 C) 6.1 x 10-3

Pa

Dissociation constant (pKa) not required; does not dissociate

Octanol/water partition coefficient 

(log Kow; 20 C)

4.83

UV/vis absorption spectrum not available
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3.3 Pesticide Use Pattern

Trifluralin is a selective, pre-emergence fluorinated dinitroaniline herbicide used to control 

annual grasses and broadleaf weeds on a variety of food crops and non-food uses, including 

residential uses. Trifluralin end-uses products for food and feed crops include emulsifiable 

concentrates (EC, 36.4; 50.8% ai) and a granular formulation (G, 10% ai). These formulations 

may be applied using ground or aerial equipment and the application timing may be dormant, 

pre-plant, or pre-emergence.

Table 3.3. Summary of Trifluralin Food Use Pattern Table

Site

Application Type

Formulation

[EPA Reg. 

No]

Maximum 

Application 

Rate (lb 

ai/A)

Max # 

Appls

Min 

Retreat

ment 

Interval 

(days)

Use Directions and 

Limitations

Cotton

Soil incorporated treatment

Preplant, postplant, or 

preemergence in spring 

Ground or aerial equipment

10% G 

[62719-131]

4lb/gal EC

[62719-250]

[33660-32]

[33660-33]

[66222-46]

5lb/gal EC

[33660-31]

1.0 1 NA Appl. of the EC formulation 

may be made alone or as a 

tank mix with other 

herbicide.

Post plant appl. may be made 

from 4 tree leaf stage up to 

layby.

A 90-day PHI has been 

established

Soil incorporated treatment

Fall prior to spring planting

Ground or aerial equipment

1.25 1 NA

Soil or water incorporated 

treatment

Preplant, postplant, or 

preemergence 

Ground or aerial equipment

2.0 2 NS Use rate for conservation 

tillage cotton only. 

Water incorporation should 

be made with a min of 0.75” 

of water.

The maximum seasonal use 

rate is 2.0 lb ai/A.

Postplant application may be 

made from 4 tree leaf stage 

up to layby.

A 90-day PHI has been 

established.

Soil incorporated treatment

Spring (preplant) or fall

Ground or aerial equipment

4lb/gal EC

[62719-250]

[33660-32]

[33660-33]

[66222-46]

5lb/gal EC

[33660-31]

2.0 2 NS Use limited to all cotton 

producing states except AZ 

and CA for control of 

rhizome Johnsongrass. 

Two year treatment program 

which consists of a double 

rate application for 2 

consecutive years.

Flax

Soil incorporated treatment

Fall (preplant)

Ground or aerial equipment

10% G 

[62719-131]

4lb/gal EC

[62719-250]

[33660-32]

[33660-33]

1.0 1 NA Animal grazing on flax straw 

is prohibited after application 

of EPA Reg. No. 33660-31, 

33660-32, 33660-33, and 

66222-46
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[66222-46]

5lb/gal EC

[33660-31]

Rapeseed (including canola and crambe)

Soil incorporated treatment

Spring (preplant) or fall 

Ground or aerial equipment

10% G 

[62719-131]

4lb/gal EC

[62719-250]

[33660-32]

[33660-33]

[66222-46]

5lb/gal EC

[33660-31]

1.0 1 NA Use prohibited in AK.

The grazing or harvesting of 

treated crop for livestock 

forage is prohibited.

The max. rate is 0.8 lb ai/A 

for EPA Reg. No. 33660-32 

and 336600-33 in MT.

Soil incorporated treatment

Spring (preplant) or fall 

Ground or aerial equipment

4lb/gal EC

[33660-32]

[33660-33]

0.8 1 NA Appl. rate is for use in MT 

only.

The grazing or harvesting of 

treated crop for livestock 

forage is prohibited.

Safflower

Soil incorporated treatment

Spring (preplant) or fall 

Ground or aerial equipment

10% G 

[62719-131]

4lb/gal EC

[62719-250]

[33660-32]

[33660-33]

[66222-46]

5lb/gal EC

[33660-31]

1.25 1 NA In MT, the max. rate is 1.0 lb 

ai/A for EPA Reg. No.

33660-31, 33660-32, and 

33660-33

Soil incorporated treatment

Spring (preplant) or fall 

Ground or aerial equipment

4lb/gal EC

[33660-32]

[33660-33]

5lb/gal EC

[33660-31]

1.0 1 NA Appl. rate is for use in MT 

only.

Sunflower

Soil incorporated treatment

Spring (preplant) or fall 

Ground or aerial equipment

10% G 

[62719-131]

4lb/gal EC

[33660-32]

[33660-33]

[62719-250]

5lb/gal EC

[33660-31]

1.0 1 NA Appl. of the EC formulations 

may be made alone or as a 

tank mix with other 

herbicides.

Use of EPA Reg. No. 33660-

32, and 33660-33 limited to 

MN, ND, and SD.
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3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

existing uses of trifluralin on canola/rapeseed, flax, mustard, sunflower, safflower, and 

cottonseed. Humans might be exposed to trifluralin in food and drinking water because trifluralin

may be applied directly to growing crops. In addition, these applications can result in trifluralin 

reaching surface and ground water, both of which can serve as a source of drinking water. The

currently registered use may result in the potential for both residential and occupational 

exposures. In an occupational setting, applicators may be exposed while handling the pesticide 

prior to an application, during an application, as well as entering in a previously treated area. 

There also may be exposure during an application and entry into previously treated residential 

(non-occupational) areas. 

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 USDA’s National Health and 

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

The most recent human health risk assessment was completed in 2004 (R. Griffin, D296628) to 

support the Tolerance Reassessment Decision (TRED) document; a scoping document was 

released in 2012 (Piper et al., 2012, D397497). Since that time, no new data have been received. 

The available toxicity database for trifluralin has been determined to be substantially complete 

and is sufficient for assessing the toxicity and characterizing the hazard of trifluralin. As part of 

the 2007 revised toxicology data requirements, acute and chronic neurotoxicity and 

immunotoxicity studies were required for trifluralin. Subsequently, the Hazard and Science 

Policy Council (HASPOC) met on March 15, 2012 to discuss data requirements for the 
Trifluralin Human Health Risk Assessment DP No. D401005

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neurotoxicity battery (acute and subchronic neurotoxicity studies) for the registration review risk 

assessment. The available data on trifluralin and other structurally related dinitroanilines do not 

indicate a concern for neurotoxicity so the HASPOC concluded that these studies are no longer 

required (Rury, 2012; TXR 0055275). The requirement for the immunotoxicity study remains 

outstanding. 

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

In the rat metabolism study on trifluralin, the focus was on urinary metabolites. The data 

indicated that the metabolic profiles were generally similar for both sexes. Many non-conjugated 

(20-30) and conjugated (10-20) urinary metabolites were recovered with the majority present at 

1-2% of the total urinary radioactivity. No single metabolite accounted for > 8-10% of the total 

urinary radioactivity and no parent compound was detected. Four metabolic pathways were 

identified: 1) oxidative N-dealkylation of one or both propyl groups and metabolites that were 

hydroxylated on the propyl side chain; 2) reduction of one or both nitro groups to the 

corresponding amine; 3) cyclization reactions to give a variety of substituted and unsubstituted 

benzimidazole metabolites; and 4) conjugation reactions, including acetylation of the reduced 

nitro groups, sulfate, and glucuronic acid conjugates.

A dermal absorption study is not available for trifluralin; however, HIARC used a 3% dermal 

absorption rate from a percutaneous absorption study in monkeys with ethalfluralin as the 

surrogate for trifluralin (TXR 0051869). 

 

4.2 Summary of Toxicological Effects

In general, the toxicity profile for trifluralin demonstrates that the kidney and the liver are the 

principal target organs in rats and dogs. In subchronic oral studies liver effects include increased 

liver weights and changes in clinical chemistry parameters. Kidney effects include decreased 

kidney weights, kidney and bladder tumors, increased BUN, increases in total protein, aspartate 

aminotransferase (AST) and lactate dehydrogenase (LDH) in the urine. Also, protein 

electrophoresis of urine samples showed α1-globulin and α2-globulin. In the kidneys, tubular 

hyaline casts, minimal cortical tubular epithelial regeneration, observed microscopically, and an 

increased incidence of progressive glomerulo-nephritis were seen. In dogs exposed to trifluralin 

for 1 year, multifocal cortical tubular cytoplasmic pigment deposition was noted in the kidneys 

of both sexes. In the subchronic studies, blood effects such as lower hemoglobin levels and 

changes in clinical chemistry were reported in rats. 

In male rats, trifluralin was associated with increased incidence of thyroid follicular cell 

combined adenoma, papillary adenoma, cystadenoma, and carcinoma tumors. It has been 

classified as a Group C (“Possible” Human Carcinogen). Extensive testing showed, however, 

that trifluralin is neither mutagenic nor genotoxic, and does not inhibit the polymerization of 

microtubules in mammalian cells. It is also not a neurotoxicant and does not appear to be an 

immunotoxicant. 
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4.3 Safety Factor for Infants and Children (FQPA Safety Factor)

As required by the Food Quality Protection Act (FQPA) of 1996, the potential of increased 

susceptibility of infants and children from exposure to trifluralin was evaluated at the 2003 

HIARC. It was concluded that the FQPA Safety Factor (SF) could be removed (1x). There was 

qualitative evidence of increased susceptibility in the rat developmental toxicity study, where 

fetal developmental effects (increased resorptions and wavy ribs) occurred in the presence of less 

severe maternal effects (decreases in body weight gain, clinical signs, and changes in organ 

weights). Qualitatively, there is also an indication of increased sensitivity in the 2-generation 

reproduction study in the rat in that offspring effects (decreased fetal, neonatal and litter 

viability) were observed at a dose level where there was less severe maternal toxicity (decreased 

body weight, body weight gain and food consumption). 

However, the Committee recommended that the FQPA SF be reduced to 1 x in assessing the 

risks posed by this chemical. The rationale for this recommendation was the low concern for 

qualitative susceptibility in the developmental rat study because the dose response was well 

characterized, the developmental effects were seen in the presence of maternal toxicity, and clear 

NOAELs/LOAELs were established for maternal and developmental toxicities. There was also a 

low concern for the qualitative susceptibility observed in the rat reproduction study since the 

dose-response was also well characterized; there was a clear NOAEL/LOAEL for maternal and 

developmental toxicities; and the effects were seen at a high-dose level (295/337 mg/kg/day). 

Offspring viability was not adversely affected in the two other 2-generation studies with 

trifluralin at dose levels up to 100 and 148 mg/kg/day. Similarly, there are no residual 

uncertainties for pre- and postnatal toxicity since the doses selected for overall risk assessment 

will address the concerns seen in these studies.

Finally, there were no data gaps in the consideration of the FQPA SF. The committee further 

recommended that a developmental neurotoxicity study was not required because in the available 

database, trifluralin does not appear to be a neurotoxic chemical. 

4.3.1 Completeness of the Toxicology Database

The toxicology database for trifluralin is sufficient for assessing risk to human health. 

Additionally, HASPOC recommended that the acute and sub-chronic neurotoxicity test should be 

waived. Consequently, the only data gap that remains is for immunotoxicity testing. 

 

4.3.2 Evidence of Neurotoxicity

HASPOC concluded, based on a weight of evidence (WOE) approach that the neurotoxicity 

battery is not required for trifluralin at this time. This decision was based on the following 

considerations: 1) lack of neurotoxicity in the available toxicology studies for trifluralin; 2) lack 

of neurotoxicity seen in chemicals of the same class; 3) the known target effects of trifluralin are 

in the kidneys; 4) the use of acute and chronic oral PODs from the rat developmental study and 

the chronic dog study, respectively, resulted in dietary risk estimates of 0.1% of the aPAD for 

females 13-49 years and 0.3% of the cPAD for children 1-2 years old, the highest subpopulation; 

5) the most sensitive endpoint (nephrotoxicity) is used for assessing risks via the non-dietary 
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exposure scenarios, and 6) considering the potential impact of these studies providing a point of 

departure (POD) lower than those used in the overall risk assessment. 

4.3.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animals

There was qualitative evidence of increased susceptibility in the rat developmental toxicity 

study, where fetal developmental effects (increased resorptions and wavy ribs) occurred in the 

presence of less severe maternal effects (decreases in body weight gain, clinical signs, and 

changes in organ weights). Also qualitatively, there is an indication of increased sensitivity in 

the 2-generation reproduction study in the rat in that offspring effects (decreased fetal, neonatal

and litter viability) were observed at a dose level where there was less severe maternal toxicity 

(decreased body weight, body weight gain and food consumption). These issues were addressed 

by the FQPA SF committee, which recommended that the FQPA SF be reduced to 1 x.

4.3.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties for pre- and postnatal toxicity since the doses selected for 

overall risk assessment will address the qualitative concerns seen in the rat developmental 

toxicity study and in the rat reproduction study.

4.4 Toxicity Endpoint and Point of Departure Selections 

A detailed description of the toxicity studies used for selecting toxicity endpoints and points of 

departure (PODs) for various exposure scenarios, as well as a detailed rationale for selection of 

the toxicity endpoints are presented in Tables 4.4.4.1.

4.4.1 Dose-Response Assessment

Endpoints selected for the non-occupational human health assessment are presented below:

Acute Reference Dose (aRfD) Established for Females 13-50 Years of Age: The endpoint used 

for establishing the acute population adjusted dose (aPAD) was selected from the developmental 

toxicity study in rats. This endpoint is considered appropriate for females of childbearing age 

(13-50 years old) since the effects could occur due to a single in utero exposure. An aPAD of 

1.0 mg/kg/day was derived from a NOAEL of 100 mg/kg/day and a 100-fold uncertainty factor 

(UF) that included a 10x-UF for interspecies extrapolations, 10x-UF for intraspecies variations, 

and a 1x FQPA SF. The LOAEL of 500 mg/kg/day was based on reduced ossification of the 

vertebrae and ribs; thickened, wavy or bent ribs; and increased total litter resorptions.

Acute Dietary Endpoint for All Populations (Including Infants and Children): A dose and 

endpoint were not selected for this risk assessment because there were no appropriate 

toxicological effects attributable to a single exposure observed in the oral toxicity studies 

including maternal effects in the developmental rat or rabbit toxicity studies. 
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Chronic Reference Dose (aRfD) for All Population: The endpoint used for establishing the 

chronic population adjusted dose (cPAD) was selected from the chronic dog feeding study. The 

cPAD of 0.024 mg/kg was derived from a NOAEL of 2.4 mg/kg/day and a 100-fold factor that 

included a 10x-UF for interspecies extrapolations, 10x-UF for intraspecies variations, and a 1x 

FQPA SF. The LOAEL of 40 mg/kg/day is based on an increased frequency of abnormal stools, 

decreased body weights and body weight gains, decreased erythrocytes and hemoglobin, and 

increased thrombocytes (males). 

A margin of exposure (MOE) of 100 is applied to all of the following residential and 

occupational oral, dermal or inhalation exposure scenarios:

Short (1-30 days) Term Incidental Oral: The endpoint used for establishing the short- and 

intermediate -term incidental oral exposure were selected from the two generation reproductive 

rat study in which the NOAEL is 200 ppm (10 mg/kg/day). The LOAEL for offspring toxicity is 

650 ppm (32.5 mg/kg/day), based on decreased pup weights in both generations and increased 

relative to body liver weights in the F2b females. 

Short (1-30 days) Term Dermal Endpoints: A study was not selected for short (1-30 days)-term 

dermal exposure because in the three dermal toxicity studies [21/28 days in rabbits (MRID 

41993810); 21/28 days in rats (MRID 00152888); and 31-days in rats (MRID 00153171), 

trifluralin was tested up to the limit dose (1000 mg/kg/day) and caused no systemic toxicity. 

HIARC also recommended that products containing trifluralin should be labeled as a 

SENSITIZER. 

Short (1-30 days) -Term Inhalation Endpoints: The endpoint used for establishing the short-term 

inhalation exposure was the 30-day inhalation toxicity study in rats. The NOAEL for this study 

was 81 mg/kg/day. The LOAEL for this study is 270 mg/kg/day based on increased 

methemoglobin and bilirubin in females and dyspnea and ruffled fur in males and females. 

4.4.2 Recommendations for Combining Routes of Exposure for Risk Assessment

As part of performing a human health risk assessment, HED considers the potential for 

concurrent trifluralin exposure via oral, dermal, and inhalation routes. When there are potential 

occupational and/or residential exposures to a pesticide, the risk assessment must address 

exposures from oral, dermal, and inhalation routes and determine whether the individual 

exposures may be combined across several exposure pathways. Short-term oral, dermal and 

inhalation should not be aggregated together because there is no dermal hazard or endpoint, and 

the incidental oral and inhalation endpoints are based on different toxicological effects. 

However, residential inhalation exposures can be aggregated with chronic dietary exposures, and 

incidental oral child exposures can be aggregated with chronic dietary exposures. 
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4.4.3 Cancer Classification and Risk Assessment Recommendations

Trifluralin has been classified as a Category C (“possible”) human carcinogen by the Cancer 

Peer Review Committee (TXR 007362) in 1987. The carcinogenic risk was quantified by the 

Q1* approach. 

4.4.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessments

Table 4.4.4.1 summarizes the toxicological doses and endpoints selected for the acute and 

chronic dietary risk assessments; the incidental short and intermediate- term oral assessments as 

well as the short, intermediate, and long-term dermal and inhalation non-occupational risk 

assessments for trifluralin. The FQPA Safety Factor Committee determined that the 10x factor 

for sensitivity to infants and children should not be retained (1x). Therefore, an MOE of 100 is 

adequate for all non-occupational exposure assessments 

4.4.5 Conclusions

The toxicity database for trifluralin is complete except for an immunotoxicity study required 

under the 2007 revised 40CFR Part 158 Toxicology Data Requirements. 

Table 4.4.4.1: Summary of Toxicological Points of Departure and Endpoints for Trifluralin for Used in Dietary and Non-dietary 

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

(Females 13-50 years of 

age)

NOAEL = 100 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF =1 

100 mg/kg/day NOAEL 

 100 (UF)

aRfD = 1.0 mg/kg/day

aPAD = 1.0 mg/kg/day 

Developmental Toxicity Study Rat 

(MRID 00151899, 00159620, 40392310)

LOAEL = 500 mg/kg/day, based on 

reduced ossification of the vertebrae 

and ribs; thickened, wavy or bent ribs; 

and increased total litter resorptions

Acute Dietary

(General population, 

including infants and 

children)

No endpoints identified from the available developments toxicity studies (rat and rabbit) appropriate for an 

acute dietary assessment for trifluralin.

Chronic Dietary

(All populations)

NOAEL = 

2.4 mg/kg/day

UFA=10x

UFH=10x

FQPA SF =1 

 2.4mg/kg/day NOAEL 

 100 (UF)

cRfD = 0.024 

mg/kg/day

cPAD = 0.024 

mg/kg/day 

Chronic (capsule) Toxicity – Dog

(MRID 42447001)

LOAEL = 40 mg/kg/day, based on 

increased frequency of abnormal stool, 

decreased body weights and body 

weight gains, and decreased 

erythrocytes and hemoglobin and 

increased thrombocytes (males)
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Table 4.4.4.1: Summary of Toxicological Points of Departure and Endpoints for Trifluralin for Used in Dietary and Non-dietary 

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

Incidental Oral 

Short-Term (1-30 days)

NOAEL = 

10 mg/kg/day

UFA=10x

UFH=10x

FQPA SF =1

Residential LOC for 

MOE = 100

Two-generation Reproduction Study in 

Rats (MRID 00151901, 00151902, 

00151903, 00159619

LOAEL = 32.5 mg/kg/day, based on 

decreased pup weights in both 

generations and increased relative to 

body liver weights in the F2b females

Dermal

Short-Term (1-30 days)

No quantification required since there was no systemic toxicity at the limit dose in the dermal toxicity 

studies. There are no developmental toxicity concerns. The HIARC also recommended that the products 

containing trifluralin should be labeled SENSITIZER

Inhalation Short-term 

(1-30 days)

NOAEL = 300

mg/m3(81 

mg/kg/day)

UFA=10x

UFH=10x

FQPA SF =1

Residential LOC for 

MOE = 100

30-Day Inhalation Study - Rat 

(MRID 40392312)

LOAEL = 1000 mg/m3(270 

mg/kg/day), based on increased 

methemoglobin and bilirubin in 

females and the incidence of dyspnea 

and ruffled fur in males and females

Cancer (oral, dermal, 

inhalation)

Classification: Group C (“Possible” Human Carcinogen)

Q 1 

* = 2.96 X 10-3 (mg/kg/day)-1 (TXR No. 00052534)

1 Explanation of Abbreviations: 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). 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 

The existing residue chemistry database for trifluralin is adequate for risk assessment purposes. 

No additional data are required at this time; however, there are some submitted data received as a 

result of a Data Call-In (DCIs) request for trifluralin which was outlined in the most recent 

residue chemistry chapter (R. Griffin, D296627, 03/04/04) that will be reviewed during the 

registration review process. The qualitative nature of the residues of trifluralin in plants and 

animals has been adequately identified, characterized and is understood. 

5.1 Residues of Concern Summary and Rationale

The HED Metabolism Assessment Review Committee (MARC) has reviewed the trifluralin

toxicology and metabolism data (03/09/04) and the recommendation is shown in Table 5.1. The 
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Agency has determined that tolerances for trifluralin residues in eggs and poultry tissue are not 

required based on the results of the respective poultry metabolism and feeding studies (CFR 

§180.6(a)(3)). 

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Primary Crop Trifluralin Trifluralin

Rotational Crop Trifluralin Trifluralin

Livestock

Ruminant

Trifluralin and metabolites 

TR-2, TR-4, TR-5, TR-6, 

TR-7, TR-14, TR-15, TR42, and TR-44

Trifluralin

Poultry Not Applicable Not Applicable

Drinking Water

Trifluralin and its major 

degradates TR-4, TR-6, 

and TR-15

Not Applicable

5.2 Food Residue Profile

No residue data were submitted with this petition. The Interregional Research Project No. 4 (IR4) has requested the conversion of the canola/rapeseed, sunflower seed and cottonseed tolerances 

to the oilseed crop group 20. The proposed use pattern for members of the rapeseed (subgroup 

20A), sunflower (subgroup 20B), and cottonseed (subgroup 20C) is similar to the existing 

registered use for canola/rapeseed, flax, mustard, sunflower, safflower, and cottonseed. 

Trifluralin has tolerances for canola/rapeseed for seed, flax, mustard, safflower, sunflower, and 

cottonseed at 0.05 ppm (40 CFR 180.207).

5.3 Water Residue Profile

EFED Drinking Water Assessment, D401006, Faruque Khan, 07/02/2012.

For the dietary risk assessment, the Environmental Fate and Effects Division (EFED) provided 

high-end, conservative estimates of drinking water concentrations (EDWCs) based on a drinking 

water assessment previously performed for the Tolerance Reassessment Eligibility Decision 

(TRED) (D296624, December 3, 2003). The EDWCs for oilseed crops are based on the 

maximum proposed application rates for aerial and ground applications specified in the proposed 

product labels (Treflan®HFP, and Treflan®TR-10). The most conservative estimates were 

obtained from aerial application of trifluralin to LA sugarcane as a surrogate scenario for Hawaii 

at the maximum labeled annual application rate of 4 lbs a.i./acre, applied twice annually at 2 lbs 

a.i./acre. The updated EDWCs for sugarcane are lower than the previously reported EDWCs in 

the TRED (U.S. EPA 2003) due to two applications at 2.0 lbs a.i./A as prescribed in current 

labels instead of 1 application at 4.0 lbs/A per year used in the previous assessment.
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The EDWCs for trifluralin and its major degradates TR-4 (α,α,α -trifluoro-5-nitro-N4,N4-

dipropyl-toluene-3,4-diamine), TR-6 (5-trifluoromethyl-3-nitro-1,2-benzenediamine) and TR-15 

(2-ethyl-7-nitro-5-(trifluoromethyl) benzimidazole) are the residues of concern in drinking water. 

The EDWCs of total toxic trifluralin residue for various crops were generated with the coupled 

models PRZM and EXAMS for surface water and SCI-GROW for ground water. The upperbound EDWCs for trifluralin and its major degradates are provided in Table 5.3 for the human 

health risk assessment. 

Table 5.3. Estimated Drinking Water Concentrations (EDWCs) of Trifluralin and its 

Degradates for Surface Water using PRZM/EXAMS and Groundwater using SCIGROW 

Drinking Water 

Source (model)

Use

Scenario 

(modeled rate)

1-in-10 year acute 

(μg/L)

1-in-10 year chronic 

(μg/L)

30- year average 

(μg/L)

Surface Water 

(PRZM/EXAMS)

Sugarcane:

FL Sugarcane STD

(2 app. X 1.0 lbs ai/acre)

3.89 (A)10.74(A) 0.59(A)

Sugarcane:

LA Sugarcane STD (2 app. 

X 1.0 lbs ai/acre)

LA Sugercane STD 2 app. 

X 2.0 lbs ai/acre)2

11.92(A)

23.83 (A)3

19.37 (G) 4

0.99(A)

1.97(A) 3

1.76 (G) 4

0.80(A)

1.59(A) 3

1.35 (G) 4

Oilseed:

CA Cotton STD 

1app. X 2.0 lbs ai/acre)3

12.82 (A) 0.35 (A) 0.33 (A)

Oilseed:

MS Cotton STD 

1 app. X 2.0 lbs ai/acre)3

21.35 (A) 1.08 (A) 0.84 (A)

Oilseed:

NC Cotton STD

1 app. X 2.0 lbs ai/acre)3

19.63 (A) 0.99 (A) 0.88 (A)

Oilseed:

ND Canola STD

1app. X 1.25 lbs ai/acre)3

8.16 (A) 0.30 (A) 0.25 (A)

Groundwater 

(SCI-GROW)

For sugarcane

(2 app. X 2.0lbs a.i./acre)

Cottonseed

1 app. X 2.0 lbs/Acre

Oil Seed

1 app. X 1.25 lbs a.i./acre

2.75E-025

1.37E-02

8.58 E-03

2.75-025

1.37E-02

8.58 E-03

2.75E-025

1.37E-02

8.58 E-03

1

= Aerial application

2

= LA Sugarcane STD scenario was used as a surrogate scenario to calculate EDWCs for trifluralin uses in Hawaii

3

= Bolded EDWCs are recommended exposure values for surface water sources for human health risk assessment

4 

= Ground application. Exposure from ground application of trifluralin is compared with aerial application for the 

highest exposure scenario (LA Sugarcane STD) for sugarcane at 4.0.lbs/a.i./A.

5

= Groundwater EDWC can be used for acute, chronic and cancer chronic concerns
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5.4 Dietary Risk Assessment

Dietary Exposure and Risk Memorandum, D410618, S. Piper, 04/02/2013

5.4.1 Description of Residue Data Used in Dietary Assessment

Tolerance level residues were used for the acute dietary assessment. For chronic and cancer 

dietary assessments, Pesticide Data Program (PDP) monitoring data were used for carrot, orange, 

orange juice, pepper, potato, and tomato which had a significant impact on the cancer exposure. 

High end modeled drinking water estimates were directly incorporated into the assessment. In 

order to assess short-term aggregate risk to trifluralin, average dietary exposure estimates (i.e., 

food and drinking water) were calculated. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

For the acute dietary exposure assessment, 100%CT was assumed for all commodities. Average 

percent crop treated estimates (D406856, J. Alsadek, 12/12/2012) were used in the chronic and 

cancer dietary risk assessments for the following crops that are currently registered for trifluralin: 

almonds: 1%; asparagus: 20%; barley: 1%; green bean: 25%; broccoli: 10%; cabbage: 40%; 

canola: 2.5%; cantaloupe: 25%; carrot: 40%; cauliflower: 10%; celery: 12.5%; corn: 1%; cotton: 

30%; cucumber: 2.5%; dry bean/pea: 10%; garlic: 5%; grapefruit: 1%; grape: 2.5%; honeydew: 

20%; lemon: 1%; onion: 2.5%; orange: 1%; peach: 1%; peanut: 5%; pecan: 1%; pepper: 25%; 

pistachio: 2.5%; potato: 2.5%; pumpkin: 5%; sorghum: 1%; soybean: 5%; squash: 5%; 

sugarbeet: 2.5%; sugarcane: 5%; sunflower: 10%; tomato: 60%; walnut: 1%; watermelon: 10%; 

and wheat: 1%. 

5.4.3 Acute Dietary Risk Assessment

An unrefined, acute dietary exposure assessment using tolerance levels, default DEEM 

processing factors, and assuming 100% crop treated (CT) for the proposed commodities was 

conducted for various population subgroups. There were no appropriate toxicological effects 

attributable to a single exposure (dose) for the general population or any other population 

subgroups except females 13-49 years old; therefore, these population subgroups were not 

included in this assessment. For food and drinking water, the acute dietary risk estimate is below 

HED’s level of concern (<100% of the acute population adjusted dose (aPAD)) at the 95th

percentile of exposure. The acute dietary exposure estimate for females 13-49 years old is less 

than 1% of the aPAD.

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary exposure and risk estimates are somewhat refined since they assume 

tolerance levels, %CT data, and DEEM default processing factors. Pesticide Data Program 

(PDP) monitoring data were used for carrot, orange, orange juice, pepper, potato, and tomato 

which had a significant impact on the cancer exposure. Combined chronic dietary exposure 

estimates for food and drinking water are well below HED’s level of concern. Using the DEEMFCID software, dietary exposure is less than 1% for the U.S. population and all infants the most 

highly exposed population subgroup.
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5.4.5 Cancer Dietary Risk Assessment

The Agency classified trifluralin as a Group C- “possible” human carcinogen. The Q1

*

is 2.96 x

10-3(mg/kg/day) -1. For food and drinking water, the cancer dietary exposure estimate for the 

U.S. population is 2.1 x 10-7.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Trifluralin

Population Subgroup

Acute Dietary

(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

N/A

0.000078 <1 0.000070 2.1x 10-7

All Infants (<1 year old) 0.000213 <1

N/A N/A

Children 1-2 years old 0.000158 <1

Children 3-5 years old 0.000128 <1

Children 6-12 years old 0.000082 <1

Youth 13-19 years old 0.000055 <1

Adults 20-49 years old 0.000070 <1

Adults 50-99 years old 0.000074 <1

Females 13-49 years old 0.002305 <1 0.000070 <1

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses at this time; however, there are existing residential uses 

that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs1

along with policy changes for body weight assumptions. The revision of residential exposures 

will impact the human health aggregate risk assessment for trifluralin. For this assessment, HED 

considered all the uses that were presented in the 2004 TRED document (D296625. S. Recore, 

Residential Exposure Assessment and Recommendations for the Tolerance Reassessment 

Evaluation Decision (TRED) Document for Trifluralin. May 6, 2004). Trifluralin can be 

purchased and used by homeowners in residential settings. The following is a list of use sites in 

the residential environment.

vegetable gardens

turf

ornamentals

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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6.1 Residential Handler Exposure/Risk Characterization

It has been determined that exposure to pesticide handlers is likely during the residential use of 

trifluralin in a variety of environments including on turf, vegetable gardens, and ornamentals. 

The anticipated use patterns and current labeling indicate several major residential exposure 

scenarios based on the types of equipment and techniques that can potentially be used to make 

trifluralin applications. The quantitative exposure and risk assessment developed for residential 

handlers is based on the scenarios as present in the 2004 Residential Exposure Assessment 

(D296625).

loading/applying granulars with a belly grinder;

loading/applying granulars with a push-type spreader; 

loading/applying granulars using a spoon, measuring scoop, shaker can, or via hand;

mixing/loading/applying liquids with a hose-end sprayer; 

mixing/loading/applying liquids with low pressure handwand sprayer; 

mixing/loading/applying liquids with backpack sprayer; and applying trifluralin 

impregnated fabric squares to soil.

HED assumes that only short-term exposures are applicable to residential handler risk 

assessments, and are considered to be protective of intermediate-term exposure and risk. The 

short-term non-cancer exposure was assessed for adults and children (see Table 6.1a). 

The Agency considers all exposure to trifluralin, including the dermal and inhalation exposure 

expected for homeowners, to have an associated carcinogenic risk. Carcinogenic risk for 

homeowner applicators is assessed based on the rates and application methods outlined above. 

An (upper-end) assumption is made that the users assessed will apply trifluralin each season, as 

labeled, for 50 years of their life. Specific methods (or scenarios) of application (spreader, 

sprayer, etc.) are assessed to demonstrate the full range of exposure due to method and area 

treated, although users are not expected to use one method for 50 years. Carcinogenic risk for 

homeowner applicators is assessed by combining dermal exposure (adjusted for an estimated 3% 

absorption based on ethalfluralin data) and inhalation exposure (100% absorption), calculating 

this exposure on a per day basis (“Lifetime Average Daily Dose”, in mg/kg/day), and then 

quantifying risk by multiplying the updated upper-bound carcinogenic potency factor (Q1*) of 

2.96 x 10-3(mg/kg/day)-1(updated in 2004, based on the Fischer 344 Rat Dietary 3⁄4’s scaling 

factor (TXR No. 0052534) by the combined exposure estimate. 

For the carcinogenic risk assessments, the Agency considers the typical application rate for a 

given use site, if known. The typical application rate is not known for most trifluralin 

applications in residential settings, therefore, with one exception, the maximum-labeled 

application rate was used for carcinogenic risk assessment. However, since the labeled rate for 

established ornamentals is 2 to 4 lbs ai/A, the Agency has used 3 lbs ai/A for the assessment of 

this scenario. 

Residential handler inhalation risk estimates (MOEs) did not exceed HED’s the level of concern 

(i.e., MOEs >100). An adult cancer exposure and risk assessment was also conducted. A 
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summary of the handler and post-application cancer risk estimates for adults ranged from 4 x 10-

11 to 2 x 10-6

are provided in Table 6.1b.
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Table 6.1a: Short-Term Residential Handler Exposure and Risk Estimates for Trifluralin

Exposure Scenario Level of 

Concern Use Site Inhalation Unit Exposure

Maximum Application 

Rate 1

Amount 

Treated or 

Handled Daily 2

Inhalation

Dose 3 MOE 4

Mixer/Loader/Applicator

Loading/Applying Granules 

with a belly grinder 100

ornamental (pre-plant)

0.039

0.000459 lbs ai/ft2

1200 ft2

0.00027 300,000

ornamental (post-plant) 0.0000918 lbs ai/ft2

0.000054 1,500,000

turf 0.0000689 lbs ai/ft2

0.00004 2,000,000

vegetable gardens 0.0000941 lbs ai/ft2

0.000055 1,500,000

Loading/Applying Granules 

with a push-type spreader 100

ornamental (pre-plant)

0.0026

0.000459 lbs ai/ft21200 ft2

0.000018 4,500,000

ornamental (post-plant) 0.0000918 lbs ai/ft21200 ft2

0.0000036 23,000,000

turf 3 lbs ai/acre 0.5 acres 0.000049 1,700,000

vegetable gardens 0.0000941 lbs ai/ft21200 ft2

0.0000037 22,000,000

Loading/applying granulars 

using a spoon 100

ornamental (pre-plant)

0.087

0.000459 lbs ai/ft21200 ft2

0.0006 140,000

ornamental (post-plant) 0.0000918 lbs ai/ft21200 ft2

0.00012 680,000

turf 0.0000689 lbs ai/acre 100 ft2

0.0000075 11,000,000

vegetable gardens 0.0000941 lbs ai/ft21200 ft2

0.00012 660,000

rose bushes 0.00043 lbs ai/bush 50 bushes 0.000023 3,500,000

Loading/applying granulars 

using a cup or shaker can 100

ornamental (pre-plant)

0.013

0.000459 lbs ai/ft21200 ft2

0.00009 900,000

ornamental (post-plant) 0.0000918 lbs ai/ft21200 ft2

0.000018 4,500,000

turf 0.0000689 lbs ai/acre 100 ft2

0.0000011 72,000,000

vegetable gardens 0.0000941 lbs ai/ft2

1200 ft2

0.000018 4,400,000

rose bushes 0.00043 lbs ai/bush 50 bushes 0.0000035 23,000,000

Loading/applying granulars

by hand 100

ornamental (pre-plant)

0.38

0.000459 lbs ai/ft21200 ft2

0.0026 31,000

ornamental (post-plant) 0.0000918 lbs ai/ft2

1200 ft2

0.00052 160,000

turf 0.0000689 lbs ai/acre 100 ft2

0.000033 2,500,000

vegetable gardens 0.0000941 lbs ai/ft2

1200 ft2

0.00054 150,000

rose bushes 0.00043 lbs ai/bush 50 bushes 0.0001 790,000

Mixing/loading/applying 

liquids with a hose-end 

sprayer; 

100 flowers, trees and shrubs

vegetable gardens

0.0014 0.047 lbs ai/gallon 5 gallons 0.000009 9,000,000
Trifluralin Human Health Risk Assessment DP No. D401005

Page 24 of 56

Table 6.1a: Short-Term Residential Handler Exposure and Risk Estimates for Trifluralin

Exposure Scenario Level of 

Concern Use Site Inhalation Unit Exposure

Maximum Application 

Rate 1

Amount 

Treated or 

Handled Daily 2

Inhalation

Dose 3 MOE 4

Mixing/loading/applying 

liquids with manually 

pressurized hand wand 

100 flowers, trees, and shrubs

vegetable gardens

0.018 0.047 lbs ai/gallon 5 gallons 0.000053 1,500,000

Mixing/loading/applying 

liquids with back pack 

sprayer

100 flowers, trees, and shrubs

vegetable gardens

0.14 0.047 lbs ai/gallon 5 gallons 0.00041 200,000

1 Based on registered non-occupational (residential) uses as assessed in the 2004 Residential Assessment (D296625)

2 Exposure Science Advisory Council Policy #9.1 and 2012 Residential Standard Operating Procedures

3 Inhalation Dose = Inhalation Unit Exposure (mg/kg) x Application Rate (lb ai/acre or ft2

or gal) x Amount Treated or Handled (A or gallons/day) /BW (80kg)

4

Inhalation MOE = Inhalation NOAEL (81 mg/kg/day)/ Inhalation Dose (mg/kg/day)
Trifluralin Human Health Risk Assessment DP No. D401005

Page 25 of 56

Table 6.1b: Cancer Residential Handler Exposure and Risk Estimates for Trifluralin

Exposure Scenario Total ADD 

(mg/kg/day)1

Total LADD

(mg/kg/day)2 Cancer Risk Estimate3

Loading/Applying 

Granules with a 

belly grinder

ornamental (pre-plant) 7.43E-02 6.52E-04 2E-06

ornamental (post-plant) 1.51E-02 1.32E-04 4E-07

turf 1.10E-02 9.69E-05 3E-07

vegetable gardens 1.51E-02 1.32E-04 4E-07

Loading/Applying 

Granules with a 

push-type spreader

ornamental (pre-plant) 1.88E-04 1.65E-06 5E-09

ornamental (post-plant) 3.66E-05 3.21E-07 1E-09

turf 5.09E-04 4.47E-06 1E-08

vegetable gardens 3.77E-05 3.31E-07 1E-09

Loading/applying 

granulars using a 

spoon

ornamental (pre-plant) 1.90E-03 1.67E-05 5E-08

ornamental (post-plant) 3.80E-04 3.34E-06 1E-08

turf 2.35E-05 2.06E-07 6E-10

vegetable gardens 3.80E-04 3.34E-06 1E-08

rose bushes 7.30E-05 6.41E-07 2E-09

Loading/applying 

granulars using a 

cup or shaker can

ornamental (pre-plant) 1.13E-04 9.92E-07 3E-09

ornamental (post-plant) 2.25E-05 1.98E-07 6E-10

turf 1.38E-06 1.21E-08 4E-11

vegetable gardens 2.27E-05 1.99E-07 6E-10

rose bushes 4.39E-06 3.85E-08 1E-10

Loading/applying 

granulars by hand

ornamental (pre-plant) 3.56E-02 3.13E-04 9E-07

ornamental (post-plant) 7.12E-03 6.25E-05 2E-07

turf 4.43E-04 3.89E-06 1E-08

vegetable gardens 7.34E-03 6.45E-05 2E-07

rose bushes 1.40E-03 1.23E-05 4E-08

Mixing/loading/app

lying liquids with a 

hose-end sprayer; 

flowers, trees and shrubs

vegetable gardens

1.10E-02 9.67E-05 3E-07

Mixing/loading/app

lying liquids with 

manually 

pressurized hand 

wand 

flowers, trees, and shrubs

vegetable gardens

5.65E-03 4.96E-05 1E-07

Mixing/loading/app

lying liquids with 

back pack sprayer

flowers, trees, and shrubs

vegetable gardens

1.14E-02 1.00E-04 3E-07

1 Total ADD (mg/kg/day) = Dermal ADD (mg/kg/day) + Inhalation ADD (mg/kg/day).

2 Total LADD (mg/kg/day) = Total ADD (mg/kg/day) × [Days per year of exposure (5 days/yr) ÷ 365 days/year] × [Years per lifetime of 

exposure (50yrs) ÷ Lifetime expectancy (78yrs)].

3 Cancer risk estimates = Total LADD (mg/kg/day) * Q1

*

, where Q1

*

= [2.96x10-3] (mg/kg/day)-1.

6.2 Post-Application Exposure

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

an environment that has been previously treated with trifluralin. The quantitative exposure/risk 

assessment for residential post-application exposures is based on the following scenarios: 
Trifluralin Human Health Risk Assessment DP No. D401005

Page 26 of 56

vegetable gardens (4.1 lbs ai/acre)

golf course turf (3 lbs ai/acre) 

turf (3 lbs ai/acre)

All residential exposures are considered to short-term duration (1-30 days).

The lifestages selected for each post-application scenario are based on an analysisprovided as an 

Appendix in the 2012 Residential SOPs2. These lifestages are not the only lifestages that could 

be potentially exposed for these post-application scenarios; however, the assessment of these 

lifestages is health protective for the exposures and risk estimates for any other potentially 

exposed lifestages. Chemical-specific TTR day was available for the trifluralin post-application 

exposure assessment. 

As noted, no acute dietary or short-term dermal points of departure have been selected for 

trifluralin; therefore; only incidental oral post-application non-cancer risk estimates for children 

1<2 years old have been provided. Non-cancer post-application scenarios assessed are as 

follows:

Incidental oral (hand to mouth, object to mouth, and soil ingestion) exposure from 

granular applications to turf using chemical-specific TTR values

Table 6.2a: Short- Term Residential Post-application Exposure and Risk Estimates for 

Trifluralin

Lifestage Post-application Exposure Scenario Dose MOEs

1 <2 year old Granular application to 

Turf

Hand to Mouth 0.00022 45,000

Object to Mouth 0.00001 730,000

Incidental Soil 

Ingestion 0.0001 98,000

Although post-application exposures to children are expected, when assessing cancer risk, the 

only adult post-application residential scenarios that are applicable, using the current methods, 

are the following:

Dermal exposure to residues on lawns

Dermal exposure to golf course turf

Dermal exposure in home vegetable gardens

Table 6.2b: Cancer Residential Post-application Exposure and Risk Estimates for Trifluralin

Lifestage Post-application Exposure Scenario LADD 1

(mg/kg/day)

Cancer Risk 2

Adult Turf Dermal 1.3E-06 4E-09

Adult Golf course Dermal 9.2E-08 3E-10

Adult Vegetable Garden- Granular Dermal 2.8E-04 8E-07

Adult Vegetable Garden- Liquid Dermal 2.8E-04 8E-07

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Trifluralin Human Health Risk Assessment DP No. D401005

Page 27 of 56

1 Dermal LADD = Dermal dose * average days of exposure (2)/year x (50) years of expected exposure/ (365 

days/year x 78 year lifetime)

2 Cancer risk estimates = LADD * Q1*

, where Q1

*

= 2.96x10-3(mg/kg/day)-1

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

There may be post-application residential exposure scenarios for trifluralin which could be 

combined for purposes of an aggregate exposure assessment. Combinations for residential 

exposure scenarios should have a reasonable probability of occurring on a single day and the pest 

that an individual is attempting to control must be considered. It is reasonable that an adult may 

treat their turf and garden on the same day. 
Trifluralin Human Health Risk Assessment DP No. D401005

Page 28 of 56

Table 6.3a: Non-Cancer Residential Handler Combined (Multiple Exposure Scenarios) Exposure and Risk Estimates for Trifluralin.

Exposure Scenarios Route of Exposure Inhalation 

Dose

Combined 

Inhalation Dose

Combined 

Inhalation MOEs

Outdoor Scenario 

(Turf/Garden)

Loading/Applying Granules with a 

belly grinder

Turf 

Garden

Inhalation

0.00004 0.000095 850,000 0.000055

Loading/Applying Granules with a 

push-type spreader

Turf 

Garden

0.000049 0.0000527 1,500,000 0.0000037

Loading/applying granulars using a 

spoon

Turf 

Garden

0.0000075 0.0001275 640,000 0.00012

Loading/applying granulars using a 

cup or shaker can

Turf 

Garden

0.0000011 0.0000191 4,200,000 0.000018

Loading/applying granulars by 

hand

Turf 

Garden

0.000033 0.000573 140,000 0.00054

Table 6.3b: Cancer Residential Handler Combined (Multiple Exposure Scenarios) Exposure and Risk Estimates for Trifluralin

Exposure Scenarios Route of Exposure LADD Combined Total 

LADD 1

Combined Total 

Cancer Risk 2

Outdoor Scenario 

(Turf/Garden)

Loading/Applying Granules 

with a belly grinder

Turf 

Garden

Inhalation 

and 

Dermal

9.69E-05

2.29E-04 7E-07 1.32E-04

Loading/Applying Granules 

with a push-type spreader

Turf 

Garden

4.47E-06

4.80E-06 1E-08 3.31E-07

Loading/applying granulars 

using a spoon

Turf 

Garden

2.06E-07

3.55E-06 1E-08 3.34E-06

Loading/applying granulars 

using a cup or shaker can

Turf 

Garden

1.21E-08

2.11E-07 6E-10 1.99E-07

Loading/applying granulars 

by hand

Turf 

Garden

3.89E-06

6.84E-05 2E-07 6.45E-05

1 Residential combined total lifetime average daily dose combines reasonably conservative, high end dermal AND inhalation handler exposures (Table 6.1) for the Turf and Garden scenarios that may 

co-occur. 

2 Cancer risk estimates = LADD * Q1*

, where Q1

*

= 2.96 (mg/kg/day)-1
Trifluralin Human Health Risk Assessment DP No. D401005

Page 29 of 56

6.4 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.4 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for trifluralin.

The recommended residential exposure for use in the adult non-cancer aggregate 

assessment reflects inhalation exposure from applying granules by hand to preplant ornamentals (Table 6.1a).

The recommended residential exposure for use in the children 1<2 years old noncancer aggregate assessment reflects hand-to-mouth exposures from granular 

application to residential turf (Table 6.2a).

The recommended residential exposure for use in the adult cancer aggregate 

assessment reflects dermal and inhalation exposure from loading/applying 

granules with a belly grinder to pre-plant ornamentals (Table 6.1b).
Trifluralin Human Health Risk Assessment DP No. D401005

Page 30 of 56

Table 6.4a. Recommendations for the Short-Term Residential Exposures for the Trifluralin Aggregate Assessment 1

Lifestage

Handler Exposure 

(mg/kg/day) 2

Residential 

Handler Total 

Exposure 

(mg/kg/day) 3

Residential 

Handler 

Total MOE 4

Post-application Exposure 

(mg/kg/day) 5

Residential Postapplication Total 

Exposure 

(mg/kg/day)

Residential Postapplication MOE 6

Dermal Inhalation Dermal Inhalation Oral

Short-Term

Adult N/A 0.0026 0.0026 31,000 N/A N/A N/A N/A N/A

Child N/A N/A N/A N/A N/A N/A 0.00022 0.00022 45,000

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Handler exposure represents high-end inhalation exposure, applying granules by hand to pre-plant ornamentals (Table 6.1a).

3 For adults, residential total exposure combines the highest dermal and inhalation exposures, where applicable. For young children, total residential exposure combines high-end 

post application incidental oral AND dermal exposure, where applicable.

4 Total MOE = 1 / (1/Dermal MOE) + (1/Inhalation MOE). Dermal NOAEL = N/A mg/kg/day; Inhalation NOAEL = 81 mg/kg/day

5 Post-application exposure represents high-end dermal, inhalation and/or incidental oral exposure for the relevant exposure duration

6 Total MOE = 1/ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental oral MOE). Dermal NOAEL = N/A mg/kg/day, Inhalation NOAEL = 81 mg/kg/day; Incidental oral 

NOAEL = 10 mg/kg/day.

Table 6.4b. Recommendations for the Residential Exposures for the Trifluralin Cancer Aggregate Assessment 1

Lifestage

Handler ADD

(mg/kg/day) 2 Residential 

Handler LADD

(mg/kg/day) 3

Residential 

Handler 

Cancer Risk 

Estimate 4

Post-application ADD 

(mg/kg/day) 2 Residential Postapplication LADD 

(mg/kg/day) 3

Residential Postapplication MOE 6

Dermal Inhalation Dermal Inhalation Oral

Short-Term

Adult 0.074 0.00027 6.52E-04 2E-06 7.9E-02 N/A N/A 2.8E-04 8E-07

1 Bolded risk estimates should contribute to the residential exposure portion of the cancer aggregate assessment. 

2 Handler exposure represents high-end dermal and inhalation dose, applying granules by with a belly grinder to pre-plant ornamentals (Table 6.1b) and Post-application exposure 

represents high-end dermal dose, 

3 LADD (mg/kg/day) = (dermal ADD (mg/kg/day)+ inhalation ADD (mg/kg/day)) × [Days per year of exposure (5 days/yr) or (2 days/yr) ÷ 365 days/year] × [Years per lifetime of exposure (50yrs) ÷ 

Lifetime expectancy (78yrs)].

4 Cancer risk estimates = Total LADD (mg/kg/day) * Q1*

, where Q1

*

= [2.96x10-3] (mg/kg/day)-1.
Page 31 of 56

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 trifluralin at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV) and low vapor pressure (6.1 x 10-3Pa). 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 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, 2010 (http://www.epa.gov/scipoly/sap/meetings/2009/120109meeting.html). 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 postapplication 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 trifluralin.

6.6 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for trifluralin. The 

Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

It is noted that the 3 lb ai/acre application rate for turf was modeled to estimate post-application 

residential exposure of children. As this rate is equal to or higher than many of agricultural 

application rates, this scenario is protective of any exposure of farm children via spray drift from 

agricultural trifluralin applications considered in this assessment.

 

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate trifluralin pesticide exposures 

and risks from three major sources: food, drinking water, and residential exposures. Separate 

residential exposure scenarios (dermal, inhalation, and oral) are combined when it is likely they 

can occur simultaneously based on the use-pattern and the behavior associated with the exposed 

population.
Page 32 of 56

7.1 Acute Aggregate Risk

Acute aggregate risks result from exposure to residues in food and drinking water alone. As a 

result, the acute aggregate risk assessment is equivalent to the acute dietary risk assessment 

discussed in Section 5.4.3 above. The risk estimate for the population subgroup Females 13-49 

years old, the only subgroup for which an acute dietary endpoint was established, is not of 

concern. The acute dietary exposure estimate for female 13-49 years old is less than 1% of the 

aPAD.

7.2 Short-Term Aggregate Risk

To estimate short-term aggregate risk, HED combined the chronic dietary (food + water) 

exposures (as a measure of average dietary exposure) with the short-term residential 

postapplication exposure for children and residential handler exposure for adults. All short-term 

exposures resulted in MOEs greater than 100 for all populations and are not of concern to HED. 

Short-term aggregate risks are summarized in Table 7.2 below.

Table 7.2 Short-Term Aggregate Risk Calculations

Population

Short -Term Scenario

LOC for 

Aggregate 

Risk1

Dietary

MOE2

MOE Oral 

Residential 

Exposure3

MOE 

Dermal 

Residential 

Exposure4

MOE 

Inhalation 

Residential 

Exposure5

Aggregate 

MOE (food, 

water, and 

residential)6

Adult 100 135,000 NA NA 31,000 25,000

Child 100 63,000 45,000 NA NA 26,000

1 An UF of 100x was applied to account for interspecies extrapolation (10x) and intraspecies variation (10x) and no 

additional UF/SF are required. See Table 4.5.4.1

2: MOE food + water = short-term oral NOAEL (10 mg/kg/day)/chronic dietary exposure from DEEM.

3: MOE oral = short-term incidental oral NOAEL (10 mg/kg/day)/hand-to-mouth residential exposure 

4: MOE dermal = NA see table 6.4a

5: MOE inhalation = short-term inhalation NOAEL (81 mg/kg/day)/residential inhalation exposure

6: Aggregate MOE (food + water + residential) =

__________________1__________________

1/MOE Dietary + 1/MOEOral + 1/MOEDermal + 1/MOEInhalation

7.3 Cancer Aggregate Risk

The aggregate cancer risk assessment for the general U.S. population takes into account 

exposure estimates from dietary consumption of trifluralin from food, residential and drinking 

water sources. Exposures from residential uses are based on the lifetime average daily dose and 

assume an exposure period of 5 days per year and 50 years of exposure in a lifetime. Average 

food+ water source dietary exposure was used. Estimated cancer risk for the general U.S. 

population includes infants and children; therefore, in accordance with HED Policy, a children’s 

cancer risk estimate was not reported separately.
Page 33 of 56

The cancer potency estimate for trifluralin is 2.96 x 10-3(mg/kg/day) -1. Aggregate cancer risk 

estimate from trifluralin residues in food and drinking water are below HED’s level of concern

for the general U.S. population.

Table 7.5 Aggregate Cancer Risk Estimates

Population

Cancer Slope 

Factor (Q1*)

(mg/kg/day)-1

Food and Water 

Exposure 

(mg/kg/day)1

Residential 

Exposure (LADD 

mg/kg/day2

Aggregate 

Cancer Risk 

(food, water, 

residential)

US Population 2.96 E-03 0.00007 0.00028 1 E-06

1

Food and water exposure may different than the chronic exposure value, since EFED calculates the water exposure 

differently.

2 Cite source of residential exposure values used in aggregate assessment (Table 6.4b).

3 Aggregate Cancer Risk = (Q1*) (Food & Water Exposure + LADD)

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to trifluralin and any other substances, and trifluralin does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed trifluralin has a common mechanism of toxicity with other 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 Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

Since this request is for a conversion of existing tolerance to a crop group tolerance, an 

occupational exposure and risk assessment was not conducted at this time, 

10.0 References

DP#: 410618

Subject: Trifluralin: Acute, Chronic, and Cancer Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessments for the Section 3 Registration Action on 

Oilseed Crop Group 20. 

From: S.Piper

To: A. Ertman and B. Madden

Date: 04/02/12

MRIDs: NA
Page 34 of 56

DP#: 401006

Subject: Drinking Water Exposure Assessment to Establish Tolerances of Parent 

Trifluralin and its Degradates for Oilseed Crop Group 20.

From: F. Khan

To: A. Ertman and B. Madden

Date: 07/02/2012 

MRIDs: NA

00044337 Emmerson, J.L.; Pierce, E.C.; McGrath, J.P.; et al. (1980) The Chronic Toxicity of 

Compound 36352 (Trifluralin) Given as a Component of the Diet to Fischer 344 Rats 

for Two Years: Studies R-87 and R-97. (Unpublished study received Sep 18, 1980 

under 1471-35; submitted by Elanco Products Co., Div. of Eli Lilly and Co., 

Indianapolis, Ind.; CDL:243289-A, 243290)

00044338 Emmerson, J.L.; Owen, N.V.; McGrath, J.D.; et al. (1980) The Chronic Toxicity of 

Compound 36352 (Trifluralin) Given as a Component of the Diet to the B6C3F1 

Mouse for 24 Months: Studies M-9067 and M-9077. (Unpublished study received Sep 

18, 1980 under 471-35; submitted by Elanco Products Co., Div. of Eli Lilly and Co., 

Indianapolis, Ind.; CDL:243291-A; 243292; 243293)

00126661 Oberly, T.; Emerson, J.; Bewsey, B.; et al. (1983) The Effect of Trifluralin 

(Compound 36352) on the Induction of Forward Mutation at the Thymidine Kinase 

Locus of L5178Y Mouse Lymphoma Cells: Study 830201MLA2055. (Unpublished 

study received Apr 5, 1983 under 1471-70; submitted by Elanco Products Co., Div. of 

Eli Lilly and Co., Indianapolis, IN; CDL:249846-C)

00124928Weisburger, J.; Weisburger, E.; Powers, M.; et al. (1977) Bioassay of Trifluralin for 

Possible Carcinogenicity: DHEW Publication No. (NIH) 78-834; Pre-RPAR Review 

Submissions #4 and #5. (Unpublished study received Nov 9, 1977 under 1471-35; 

prepared by U.S. National Institutes of Health, National Cancer Institute, Div. of 

Cancer Cause and Prevention, Carcinogenesis Testing Program and others, submitted 

by Elanco Products Co., Div. of Eli Lilly and Co., Indianapolis, IN; CDL:233235-A; 

233234)

00132820Bridge, T.; van Lier, R.; Adams, E.; et al. (1982) Percutaneous Absorption of 14CEthalfluralin (EL-161, Compound 94961) in Monkeys: Studies M-6162 and P03282. 

(Unpublished study received Dec 2, 1983 under 4F3006; submitted by Elanco 

Products Co., Div. of Eli Lilly and Co., Indianapolis, IN; CDL:072180-B)

00133426 Neal, S.; Emmerson, J.; Probst, G.; et al. (1983) The Effect of Trifluralin (Compound 

36352) on the in vivo Induction of Sister Chromatid Exchange in Bone Marrow of 

Chinese Hamsters: Study 830207SCE2055. (Unpublished study received Dec 9, 1983 

under unknown admin. no.; submitted by Elanco Products Co., Div. of Eli Lilly and 

Co., Indianapolis, IN; CDL:251921-K)
Page 35 of 56

00148318 Young, R. (1984) Evaluation of Triflurex Technical (Trifluralin) in the 

CHO/HGPRT Forward Mutation Assay: Final Report: LBI Project No. 22207. 

Unpublished study prepared by Litton Bionetics, Inc. 27 p.

.

00148319 Moore, M. (1984) Evaluation of Triflurex Technical in the Rat Dominant Lethal 

Assay: Final Report: Project No. 22203. Unpublished study prepared by Litton 

Bionetics. 69 p.

00148320 Ivett, J. (1984) Mutagenicity Evaluation Triflurex Technical, Batch No. 5320 in the 

Bone Marrow: Cytogenic Assay: Final Report: LBI Project No. 22202. Unpublished 

study prepared by Litton Bionetics. 32 p.

00148345 Jagannath, D. (1984) Mutagenicity Evaluation of Triflurex Tech (Trifluralin) Batch 

5230 in the Ames Salmonella/Microsome Plate Test: Final Report: LBI Project No. 

20988. Unpublished study prepared by Litton Bionetics, Inc. 19 p.

00151894 Mellano, D. (1982) Study of the Capacity of the Test Article HOE 38474 OH at 208 

to Induce "Unscheduled DNA Synthesis" in Cultured Hela Cells: Study No. M 372. 

Unpublished study prepared by Istituto Di Ricerche Biomediche "Antoine Marxer" 

S.p.A. 19 p.

00151895 Leist; Weigand; Kramer (1981) Testing of Hoe 38474 - Active Ingredient for 

Mutagenicity in the Micronucleus Test following Oral Administration to NMRI Mice: 

(Code: HOE 38474 OH AT 208): Report No. 285/81. Unpublished report prepared by 

Hoechst Aktiengesellschaft. 16 p.

00151896 Horstmann (1984) Dominant-lethal Test for Determination of Mutagenic Effect in 

Male NMRI-mice after Oral Administration: Trifluralin: Code: Hoe 38474 OHZD99 

0002: Report No. 84.0763. Un- published report prepared by Hoechst 

Aktiengesellschaft. 89 p.

00151898Fumero, S. (1982) Study of the Mutagenic Activity "In Vitro" of the Compound HOE 

38474 OH AT 208 with Schizosaccharomyces Pombe: Study No. M 374. 

Unpublished study prepared by Instituto Di Ricerche Biomediche "Antoine Marxer" 

S.p.A. 16 p.

00151899Baeder, Weigand, Kramer (1983) Testing for Embryotoxicity in Wister Rats following 

Oral Administration: HOE 38474 - Active Ingredient: Report No. 83.0557: Study 

No.G2R0383. Unpublished study prepared by Hoechst Aktiengesellschaft. 51 p.

00151901 Becker, H. (1984) Multiple Generation Study in the Rat: Trifluralin Substance 

TechnicalGrade (Code : HOE 38474 OH AT210): Project No. 008875. Unpublished 

study

prepared by Research & Consulting Co., AG. 604 p.

00151902 Ellgehausen, H. (1984) Determination of Trifluralin Substance Technical 

Grade (Code : HOE 38474 O H T210) in Rodent Feed: Project No. 008875. 

Unpublished study prepared by Research & Consulting Co. 26 
Page 36 of 56

00151903 Westen, H. (1984) Multiple Generation Study in Rat: Trifluralin Substance

Technical Grade (Code: HOE 38474 O H AT210): Pathology Report Part II: Project 

No008875. Unpublished study prepared by Research & Consulting Co., AG. 704 p.

00151904 Ullmann, L. (1982) 30 Day Repeated Dose Inhalation Toxicity Study with HOE 

38474 OH AT 210 Active Ingredient (Technical) in Rats: Part 1: Project No. 005488. 

Unpublished study prepared by Research & Consulting Co., Ltd. 400 p.

00151905 Suter, P. (1983) 13-Week Toxicity Study with Trifluralin (HOE 38474 O H AT210) in 

Mice following Dietary Administration: Report: Project No. 008842. Unpublished study 

prepared by Research & Consulting Co., AG. 223 p.

00151906 Schutz; Weigand; Kramer (1980) Repeated-dose (3 Months) Oral Toxicity Study of 

the Active Substance HOE 38474 (Code: HOE 38474 O H AT204) Administered in 

the Feed to Rats: Report No. 618/80. Unpublished study prepared by Hoechst 

Aktiengesellschaft. 422 p.

00151907 Brunk; Weigand; Kramer (1981) Toxicology Testing of Trifluralin (Hoe 38474 

OH AT 204) by Repeated Oral Administration to Beagle Dogs for Six Months: Report No. 

636/81. Unpublished report prepared by Hoechst Aktiengesellschaft. 742 p

00151908Bathe, R. (1984) 12-Month Oral Toxicity (Feeding) Study in Beagle Dogs: Trifluralin 

Substance Technical Grade (Code: HOE 38474 O H AT210): Project No. 008864: 

Report Part 1. Unpublished study prepared by Research & Consulting Co. 439 p

00152419 Byrd, R. (1984) A Teratology Study of Trifluralin (El-152, Compound 36352) 

Administered Orally to Charles River CD Rats: Study R08484. Unpublished study 

prepared by Lilly Research Labs. 308 p.

00152421 Byrd, R. (1984) A Teratology Study (II) of Trifluralin (El-152, Compound 36352) 

Administered Orally to Dutch Belted Rabbits: Study B01784. Unpublished study 

prepared by Lilly Research Labs. 223 p.

00153171 Suter, P. (1982) 31 Days Dermal Toxicity Study with Hoe 38474 OH AT 210 Active 

Ingredient (Technical) in Rats: Project 005490. Unpublished study prepared by 

Research & Consulting Co., Ltd. 450 p.

00152888 Negilski, D. (1985) Subchronic (21-day) Dermal Toxicity Study in New Zealand 

White Rabbits with Technical Trifluralin: Study B00184. Unpublished study prepared 

by Lilly Research Laboratories. 222 p.

00153173 Engelbart (1979) Test for Mutagenicity in Bacteria Strains in the Absence and 

Presence of a Liver Preparation: Hoe 38474 OH AT204 (Active Ingredient) 

Trifluralin: Report No. 74/79. Unpublished study prepared by Hoechst AG. 7 p.

00155261 Leist, K. (1981) Four Hour LC50 Aerosol Inhalation Toxicity Study in Rats on HOE 

38474 OH at 210 Active Ingredient (Technical): Report: Project 005477. 

Unpublished study prepared by Research & Consulting Co. Ltd. 37 p.
Page 37 of 56

00157154 Jordan, W. (1983) A Preliminary Dietary Study of the Effects of Trifluralin on the 

Urinary Tract of Male Fischer 344 Rats: Study No. R15083: Report No. 1. 

Unpublished study prepared by Lilly Research Labs. 89 p.

00157156 Usher, R. (1985) A Special Urinalysis Study in Fischer 344 Rats Maintained on Diets 

Containing Trifluralin (Compound 36352) for Three Months: Study No. R04785. 

Unpublished study prepared by Lilly Research Labs. 711 p.

00157482 Vigna, E. (1985) Trifluralin Technical: Acute Dermal Toxicity Study in Rats: RBM 

Exp. No. 2159. Unpublished study prepared by Istituto di Ricerche Biomediche 

"Antoine Marxer", RBM S.p.A. 13 p.

00157483 Vigna, E. (1985) Trifluralin Technical: Acute Eye Irritation Study in Rabbits: RBM 

Exp. No. 2160. Unpublished study prepared by Istituto di Ricerche Biomediche 

"Antoine Marxer", RBM S.p.A. 15 p.

00157484 Bassi, L. (1985) Trifluralin Technical: Dermal Sensitization Study in Guinea Pigs: 

RBM Exp. No. I 892. Unpublished study prepared by Istituto di Ricerche Biomediche 

"Antoine Marxer", RBM S.p.A. 15 p.

00157485 Vigna, E. (1985) Trifluralin Technical: Acute Dermal Irritation Study in Rabbit: 

RBM Exp. No. 2161. Unpublished study prepared by Istituto di Ricerche Biomediche 

"Antoine Marxer", RBM S.p.A. 13 p.

00157486 Vigna, E. (1985) Trifluralin Technical: Acute Toxicity Study by Oral Route in Rats: 

RBM Exp. No. 2162. Unpublished study prepared by Istituto di Ricerche Biomediche 

"Antoine Marxer", RBM S.p.A. 13 p.

00158935 Suter, P. (1986) Oncogenicity Study with Trifluralin Active Ingredient Technical 

(HOE 38474 O H AT210) in Mice: Project No. 008853. Unpublished study prepared 

by Research & Consulting Company AG. 6478 p.

00159616Ebert, E. (1985) Trifluralin-Active Ingredient Technical Testing for Acute Delayed 

Neurotoxicity in White Leghorn Hens: Report No. 85.0742. Unpublished study 

prepared by Hoechst AG. 38 p.

00159618 Bathe, R. (1985) Trifluralin, Substance Technical Grade: 12-Month Oral Toxicity 

(Feeding) Study in Beagle Dogs: Concentration of Trifluralin, Substance Technical 

Grade in Dog Feed¿: Project No. 008864: Report No. A32778. Unpublished study 

prepared by Research & Consulting Co. AG. 4 p.

00159619Becker, H. (1985) Trifluralin, Substance Technical Grade: Multiple Generation Study 

in the Rat: Diet Preparation, Stability, and Analysis of the Test Article¿: 1st 

Amendment to Report: Project No. 008875: Report No. A32777. Unpublished study 

prepared by Research & Consulting Co. AG. 4 p

00159620 Baeder; Mayer (1986) Testing for Embryotoxicity in Wistar Rats following Oral 

Administration of Hoe 38474: Incidence of Wavy Ribs in Control Studies and at Dose 

Levels Toxic to Either Dams or Embryos: Supplement to Report No.83.0557: Report 

No. 86.0166.Unpublished study prepared by Hoechst AG. 15 p.

00162458 Donaubauer (1986) Carcinogenicity Study in Rats (28-month Feeding Study): 

Trifluralin: Study No. 680: Report No. 85.0087. Unpublished study prepared by 

Hoechst Aktiengesellschaft, Pharma Forschung Toxikologie. 3126 p.
Page 38 of 56

00162543 Hoyt, J. (1986) A One-year Two-generation Reproduction Study in CD Rats 

Maintained on Diets Containing Trifluralin (EL-152, Com- pound 36352): Studies 

R06384 and R13984. Unpublished study prepared by Lilly Research Laboratories. 

778 p.

00162457 Donaubauer (1986) Chronic Feeding Study (24 Months) in Rats: Trifluralin: Study

No. 680: Report No. 85.0302. Unpublished study prepared by Hoechst 

Aktiengellschaft, Pharma Forschung Toxikologie. 1837 p.

40138301 Usher, R. (1986) A Supplementary Report of a Special Urinalysis Study in Fischer 

344 Rats Maintained on Diets Containing Trifluralin (Compound 36352) for Three 

Months: Study R04785. Unpublished study prepared by Lilly Research Laboratories. 

263 p.

40334707 Loveday, K. (1987) Evaluation of Trifluralin in the Ames Mutagenesis Assay: ADL 

Reference: 88720-68. Unpublished study prepared by Arthur D. Little, Inc. 28 p.

40392310 Leist, K.; Penseler, D.; Mayer (1987) Trifluralin Substance Technical Grade (Code: 

HOE 38474 OH AT210): Testing for Embryotoxicity in Wistar Rats following Oral 

Administration: Supplementary Data in Support of Previously Submitted Study Acc. 

No. 258993: Laboratory Project No. 87.0997, Report No. A 36041. Unpublished 

study prepared by Hoechst Aktiengesellschaft. 19 p.

40392312 Ullman, L. (1987) 30-Day Repeated Dose Inhalation Toxicity Study with HOE 38474 

OH at 210 in Rats: Amended Version of Previously Submitted Study Acc. No. 

258996: Laboratory Project No. 005488, Report No. A 22688 and A 36084. 

Unpublished study prepared by Research & Consulting Co. Ag. 711 p.

40392313Suter, P.; Horst, K.; Vogel, W.; et al. (1987) Oncogenicity Study with Trifluralin 

Active Ingredient Technical (HOE 38474 OH AT210) in Mice: Supplementary Data in 

Support of Previously Submitted Study Acc. No. 262516-262520: Laboratory Project 

No. 008853, Report No. A 36197. Unpublished study prepared by Research & 

Consulting Co. AG. 47 p.

40405007 Rubin, Y.; et al. (1987) Triflurex: Two-generation Reproduction Study in theRat: 

Laboratory Project ID AGN/125/TRI. Unpublished study prepared by Life Science 

Research Israel Ltd. 1664 p.

40673701 Adams, E.; Glass, S.; Van Lier, R. (1988) Percutaneous (Dermal) Absorption of 

Carbon 14-Trifluralin in Rhesus Monkeys: Laboratory Project ID: P07487 and 

P03087. Unpublished study prepared by Lilly Research Laboratories. 55 p.

40765601 Young, R. (1988) Mutagenicity Test on Trifluralin Technical Grade: Batch Number 

39 in the CHO/HGPRT Foreward Mutation Assay: Project ID. 10137-0-435. 

Unpublished study prepared by Hazleton Laboratories America, Inc. 46 p.

40765602 Cifone, M. (1988) Mutagenicity Test on Trifluralin, Technical Grade in the Rat 

Primary Hepatocyte Unscheduled DNA Synthesis Assay: Project ID. 10137-0-447. 

Unpublished study prepared by Hazleton Laboratories America, Inc. 39 p.

40765603 Ivett, J. (1988) Mutagenicity Test on Trifluralin Technical Grade in the Mouse Bone 

Marrow and Spermatogonial Cell Cytogenetics Assay: Project ID. 10137-0-473. 

Unpublished study prepared by Hazleton Laboratories America, Inc. 51 p.
Page 39 of 56

40822202 Adams, E. and Poulsen, R. G. (1988) The Acute Dermal Toxicity and Primary 

Dermal Irritation of Technical Trifluralin in the New Zealand White Rabbit. 

 Unpublished study prepared by Lilly Research Laboratories, 18p.

41086101 Adams, E.; Bendele, R.; Emmerson, J. (1989) Reanalysis and Discussion of Urine 

Protein Electrophoresis Data from a Special Urinalysis Study in Fischer 344 Rats with 

Trifluralin (Compound 36352). Unpublished supplemental submission prepared by 

Lilly Research Laboratories 63p.

41218901 Magnussen, J. (1989) Identification of the Urinary Metabolites of carbon 

14Trifluralin in Rats: Project ID: Experiment ABC-0433. Unpublished study prepared 

by Lilly Research Laboratories. 53 p.

41993810 Vedula, U.; Kociba, R.; Bond, D. (1991) XRM-5313: A Formulation Containing 

Trifluralin and XRD-498--21 Day Dermal Study in New Zealand White Rabbits: Lab 

Project Number: M-005313-003A. Unpublished study prepared by The Dow Chemical 

Co., Tox. Research Lab. 166 p.42447001 Adams, E.; Bernhard, N.; Jordon, W. 

(1992) A Chronic Toxicity Study of Trifluralin (Compound 036352) Administered 

Orally to Beagle Dogs for One Year (Supp.): Lab Project Number: D07190. 

Unpublished study prepared by Lilly Research Labs. 470 p.

42972701 Shapiro, R. (1993) EPA Acute Oral Toxicity-Defined LD50 in Rats: Trilin 5, Lot 

#227284: Lab Project Number: T--2527: 2527: P320. Unpublished study prepared by 

Product Safety Labs. 34 p.

42972702 Shapiro, R. (1993) EPA Acute Dermal Toxicity Limit Test: Rabbits: Trilin 5, Lot 

227284: Lab Project Number: T--2530: 2530: P322. Unpublished study prepared by 

Product Safety Labs. 20 p.

42972703 Shapiro, R. (1993) EPA Acute Inhalation--Defined LC50: Rats: Trilin 5, Lot # 

227284: Lab Project Number: T--2532. Unpublished study prepared by product Safety 

Labs. 54 p.

42972704 Shapiro, R. (1993) EPA Primary Eye Irritation: Rabbit: Trilin 5, Lot #227284: Lab 

Project Number: T--2528: P324: E30715-1. Unpublished study prepared by Product 

Safety Labs. 30 

42972705 Shapiro, R. (1993) EPA Primary Dermal Irritation Test: Rabbits: trilin 5, Lot 227284: 

Lab Project Number: T--2529: 2529: P326. Unpublished study prepared by Product 

Safety Labs 23 p.

42972706Shapiro, R. (1993) EPA Topical Skin Sensitization Test in Guinea Pigs (Buehler): 

Trilin 5, Lot #227284: Lab Project Number: T--2531: 2531. Unpublished study 

prepared by Product Safety Labs. 33 p.

43447301 Kuhn, J. (1994) Trific 10G: Acute Oral Toxicity Study in Rats: Lab Project Number: 

0875-93. Unpublished study prepared by Stillmeadow, Inc. 11 p.

43447302 Kuhn, J. (1994) Trific 10G: Acute Dermal Toxicity Study in Rabbits: Lab Project 

Number: 0876-93. Unpublished study prepared by Stillmeadow, Inc. 11 p.

43447303 Holbert, M. (1994) Trific 10G: Acute Inhalation Toxicity Study in Rats: Lab Project 

Number: 0877-93. Unpublished study prepared by Stillmeadow, Inc. 20 p.
Page 40 of 56

43447304 Kuhn, J. (1994) Trific 10G: Primary Eye Irritation in Rabbits: Lab Project Number: 

0878-93. Unpublished study prepared by Stillmeadow, Inc. 18 p.

43447305 Kuhn, J. (1994) Trific 10G: Primary Dermal Irritation in Rabbits: Lab Project 

Number: 0879-93. Unpublished study prepared by Stillmeadow, Inc. 12 p. 43447306 

Kuhn, J. (1994) Trific 10G: Dermal Sensitization Study in Guinea Pigs: Lab Project 

Number: 0880-93. Unpublished study prepared by Stillmeadow, Inc. 17 p.

44135107 Adams, E.; Markham, J. (1996) A One-Year Two-Generation Reproduction Study in 

CD Rats Maintained on Diets Containing Trifluralin: Supplement #1 to MRID No. 

00162543: Lab Project Number: R06384: R13984-S1: R13984. Unpublished study 

prepared by Lilly Research Labs. 16 p

92062028 Environ Corp. (1990) Dowelanco Phase 3 Summary of MRID 00132820. 

Percutaneous Absorption of (Carbon-14) - Ethalfluralin in Monkeys: M-6162 and 

P03282. Prepared by LILLY RESEARCH LABS. 7 p

IARC (1991) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 

Trifluralin, Vol 53, 1991

USEPA (1979) Trifluralin (Treflan®) Position Document 1/2/3, 44 FR 50911, NTIS # 

PB80-213937, Aug 30, 1979.

USEPA (1982) Alpha, alpha, alpha-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine, Trifluralin 

(Treflan®) Position Document 4, 47 FR 33777, NTIS# PB82-263252, Aug 4, 

1982.

MEMORANDUM

Jaeger, R.B. (1986). Peer Review of Trifluralin, dated April 11, 1986. TXR No. 0005578. 

Rowland, J. and Doyle, E. (2003). Trifluralin (P.C. Code 036101): Report of the Hazard 

Identification Assessment Review Committee, dated May 2, 2003; TXR 

No. 0051869. 

Fricke, R. (2003). Trifluralin: Toxicology Disciplinary Chapter for the Tolerance Reassessment 

Eligibility Decision Document, dated October 2, 2003.

Piper, S. (2004). Trifluralin: Metabolism Assessment Review Committee Briefing 

Memorandum, dated January 6, 2004.

Griffin, R (2004). Trifluralin: Human Health Risk Assessment. DP Barcode 296628, dated May 

7, 2004.

Brunsman, L. (2004). Trifluralin: Quantitative Risk Assessment (Q1

*

) based on Fischer 344 Rat 

Dietary Studies With 3⁄4’s Scaling Factors, dated May 8, 2003. TXR No. 

0051890. 

Brunsman, L. (2004). REVISED Trifluralin: Quantitative Risk Assessment (Q1

*

) based on 

Fischer 344 Rat Dietary Studies With 3⁄4’s Scaling Factors, dated May 11, 

2004. TXR No. 0052534. 
Page 41 of 56

Copley, M. (2007). Trifluralin: Corrected DERs and Executive Summaries, dated August 27, 

2007. TXR No. 00547000. 

Rury, K. (2013). Trifluralin: Summary of Hazard and Science Policy Council 

(HASPOC) Meetings of March 6, 2012: Recommendations on the 

need for the neurotoxicity battery (acute and subchronic neurotoxicity 

studies) TXR No. 0055275.

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for [Type of Use (e.g., food vs. non food)] for Trifluralin are in 

Table A.1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols 

were used.

Table A.1 Toxicology Data Requirements for Trifluralin

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity......................................................

870.1200 Acute Dermal Toxicity.................................................

870.1300 Acute Inhalation Toxicity.............................................

870.2400 Primary Eye Irritation...................................................

870.2500 Primary Dermal Irritation .............................................

870.2600 Dermal Sensitization ....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)..............................................

870.3150 Oral Subchronic (nonrodent)........................................

870.3200 21/28-Day Dermal........................................................

870.3250 90-Day Dermal.............................................................

870.3465 90-Day Inhalation.........................................................

yes

yes

yes

no

no

yesa

yesb

yes

---

Waived/Yes (c)

870.3700 Developmental Toxicity (rodent) .................................

870.3700 Developmental Toxicity (nonrodent) ...........................

870.3800 Reproduction ................................................................

yes

yes

yes

yes

yes

yes

870.4100 Chronic Toxicity (rodent).............................................

870.4100 Chronic Toxicity (nonrodent).......................................

870.4200 Oncogenicity (rat).........................................................

870.4200 Oncogenicity (mouse) ..................................................

870.4300 Chronic/Oncogenicity (mouse) ....................................

870.4500 Chronic/Oncogenicity (rat)...........................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial....................

870.5300 Mutagenicity—Gene Mutation - mammalian...............

yes

yes

yes

yes

870.5375 Mutagenicity—Structural Chromosomal Aberrations..

870.5385 Mutagenicity—Structural Chromosomal Aberrations..

870.5395 Mutagenicity—Other Genotoxic Effects......................

870.5550 Mutagenicity—Other Genotoxic Effects......................

yes

yes

yes

yes

Yes

yes

yes

yes

870.6100 Acute Delayed Neurotox. (hen)....................................

870.6100 90-Day Neurotoxicity (hen) .........................................

870.6200 Acute Neurotox. Screening Battery (rat)......................

870.6200 Chronic Neurotox. Screening Battery (rat)...................

yes

no

yes

yes

Yes

---

Waived/yes c

Waived/yes c
Page 42 of 56

Test Technical

Required Satisfied

870.6300 Develop. Neuro ............................................................ no ---

870.7485 General Metabolism .....................................................

870.7600 Dermal Penetration.......................................................

870.7800 Immunotoxicity

yes

no

yes

Yes

---

no

a Guideline satisfied by the findings of the 24-month carcinogenicity study in mice (MRID 40392313).

 b Guideline satisfied by the findings of the 1-year oral study in dogs (MRID 42447001).

 c Data requirement waived by HASPOC , March 6, 2013 ( TXR No. 0055275).
Page 43 of 56

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Studies for Trifluralin, Technical

Guideline 

No. Study Type MRID No. Results

Toxicity 

Category

870.1100 Acute Oral (Rat) 00157486 (1985)

Acceptable/Guideline

LD50 > 5000 mg/kg

IV

870.1200 Acute Dermal (Rat) 00157482 (1985)

Acceptable/Guideline

LD50 > 2000 mg/kg

III

 870.1200 Acute Dermal (Rabbit)

00158820 (1985)

Acceptable/guideline

LD50 > 2000 mg/kg

 III

 870.1200 Acute Dermal (Rabbit) 40822202 (1988)

Acceptable/guideline

LD50 > 5000 mg/kg

 IV

870.1300 Acute Inhalation (Rat) 00155261 (1982)

Acceptable/guideline

LC50 > 4660 mg/m3, 4.66 

mg/L

IV

870.2400 Primary Eye Irritation 

(Rabbit)

00157483 (1985)

Acceptable/Guideline

Conjunctival redness at 

24hr, cleared by 4 days

III

870.2500 Primary Skin Irritation 00157485 (1985)

Acceptable/Guideline

Not an irritant

IV

870.2600 Dermal Sensitization 00157484 (1985)

Acceptable/Guideline

Sensitizing agent

N/A
Page 44 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.3100

2-Week R-F Feeding -

Rats (male)

00157154 (1983)

0, 6500 ppm

range-finding study for 00157156 

(1985), 41038301 (1986)

Acceptable/Nonguideline

NOAEL = not achieved

LOAEL = 6500 ppm based on renal epith damage,

urine triple phosphates crystals and urinary 

sediment

870.3100

90-Day Oral toxicity -

Rat

00151906 (1980)

0, 800, 2000, or 5000 ppm

M: 0, 59, 154, and 392 mg/kg/day 

F: 0, 69, 168, and 421 mg/kg/day

Acceptable/Guideline

NOAEL = 2000 ppm (154/168 mg/kg/day, M/F)

LOAEL = 5000 (392/421 mg/kg/day, M/F)

Based on minor decreases in overall body weight 

gains and food consumption in males and females, 

decreased hemoglobin, alkaline phosphatase, and 

alanine aminotransferase in the males, and 

increased absolute and relative (to body) liver 

weights in males and females. 

870.3200

21/28-Day dermal 

toxicity-rabbit

41993810 (1991)

0, 100, 500, or 1000 mg/kg /day,

[formulation containing 35.8% 

trifluralin and 2.6% XRD-498]

Acceptable/Guideline

Systemic NOAEL =1000 mg/kg/day

Systemic LOAEL = Not achieved

Dermal NOAEL = Not achieved

Dermal LOAEL = 100 mg/kg/day, edema, and/or 

scaling and fissuring 100 mg/kg/day based skin 

irritation

870.3200

31-Day dermal toxicityrat

00153171 (1982)

0, 40, 200, or 1000 mg/kg/day

Acceptable/Guideline

Systemic NOAEL = 1000 mg/kg/day (limit dose)

Systemic LOAEL = not achieved

Dermal NOAEL = 40 mg/kg/day.

Dermal LOAEL = 200 mg/kg/day based on subepidermal inflammation and ulcerations in males 

and females. 

870.3200

21/28-Day dermal 

toxicity-rat

00152888 (1985)

0, 1000 mg/kg/day (limit dose)

Acceptable/Guideline

Systemic NOAEL = 1000 mg/kg/day.

Systemic LOAEL = Not achieved

Dermal NOAEL= Not achieved

Dermal LOAEL = 1000 mg/kg/day (limit dose) based on erythe

870.3465

30-Day inhalation 

toxicity

40392312 (1987) reformat of 

00151904 (1982) 

0, 100, 301, 1006 mg/m3 

(6 hours/day 5 days/week for up to 

30 days)

Acceptable/Nonguideline

NOAEL = 301 mg/m3(81 mg/kg/day)

LOAEL = 1006 mg/m3(300 mg/kg/day) based on 

increased methemoglobin and bilirubin in females 

and incidences of dyspnea and ruffled fur in males 

and females. 
Page 45 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.3700 [83-3(a)]

Developmental Toxicity 

Study - Rat

00151899 (1983), 00159620 

(1986), 40392310 (1987)

0, 20, 100, 500 mg/kg/day

Acceptable/Guideline

Systemic Maternal NOAEL = 100 mg/kg/day

Systemic Maternal LOAEL = 500 mg/kg/day 

based on mortality, clinical signs, decreased body 

weight gains, decreased food consumption, and 

increased liver and spleen weights,

Developmental NOAEL =100 mg/kg/day.

Developmental LOAEL = 500 mg/kg/day based on

 reduced ossification of the vertebrae and ribs and 

thickened, wavy or bent ribs and increased of 

incidences of total resorptions

870.3700 [83-3(a)]

Developmental Toxicity 

Study - Rat

00152419 (1984)

0, 100, 225, 495, or 1000 

mg/kg/day

Acceptable/Guideline 

Maternal NOAEL = 495 mg/kg/day

Maternal LOAEL = 1000 mg/kg/day based

decreased body weights and decreased food 

consumption. 

Offspring NOAEL = 495 mg/kg/day

Offspring LOAEL = 1000 mg/kg/day based on

decreased fetal body weights. 

Developmental NOAEL = 1000 mg/kg/day

Developmental LOAEL was not established.

870.3700 [83-3(b)]

Developmental Toxicity -

Rabbit

00152421 (1984)

0, 100, 225, 500 mg/kg/day

Acceptable/Guideline 

Maternal NOAEL = 100 mg/kg/day

Ma Maternal LOAEL = 225 mg/kg/day based on 

abortions, macroscopic changes in the liver and 

lungs, and decreased food consumption abortions, 

macroscopic changes in the liver and lungs, and 

decreased food consumption. 

Developmental NOAEL = 100 mg/kg/day

Developmental LOAEL = 225 mg/kg based on 

abortions. 
Page 46 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.3800 [83-4]

2-Gen Repro - Rat

00151901 (1984)

00151902 (1984) Feed analysis

00151903 (1984) Path

00159619 (1985) Supplement

0, 200, 650, 2000 ppm

0, 20, 32.5, 200 mg/kg/day

(1 ppm = 0.5 mg/kg/day)

Acceptable/Guideline

Parental NOAEL = 200 ppm (10 mg/kg/day).

Parental LOAEL = 650 ppm (32.5 mg/kg/day)

based on mortality due to acute renal failure and 

increased lesions of the renal proximal tubules in 

the F1 females; increased relative (to body) weights 

of the liver, kidney (males), and testes in both 

generations. 

Offspring NOAEL = 200 ppm (10 mg/kg/day)

Offspring LOAEL = 650 ppm (32.5

mg/kg/day) based on decreased pup weights in both 

generations and increased relative to body liver 

weights in the F2b females

Repro NOAEL = 2000 ppm (100 mg/kg/day)

Repro LOAEL = Not established. 

870.3800 [83-4]

2-Gen Repro - Rat

00162543 (1986) 

44135107 (1996)

0, 200, 630, 2000 ppm

0, 15, 47, 148 mg/kg/day

Acceptable/Guideline

Parental NOAEL = 200 ppm (15 mg/kg/day)

Parental LOAEL = 630 ppm (47 mg/kg/day), based

on decreased BWG and food consumption 

Offspring NOAEL = 200 ppm (15 mg/kg/day)

Offspring LOAEL = 630 ppm (47 mg/kg/day)

based on small pup size in 3 litters

Repro NOAEL = 2000 ppm (148 mg/kg/day)

Repro LOAEL = Not established

870.3800 [83-4]

2-Gen Repro - Rat

40405007 (1987) 

0, 50, 450, 4000 ppm

M: 0, 3.9, 35, 295 mg/kg/day

F: 0, 4.7, 42, 337 mg/kg/day 

Acceptable/Guideline

Parental NOAEL = 450 ppm [35/42 mg/kg/day

 M/F]

Parental LOAEL = 4000 ppm [295/337 mg/kg/day 

M/F] based on decreased body weights, body 

weight gains, food consumption, and food 

efficiency in males and females of both 

generations; decreased ovary weights in both 

generations; colon distension in the F1 males; and 

uterine atrophy in the females of both generations.

Offspring NOAEL = 450 ppm (35/42 mg/kg/day M/F]

Offspring LOAEL = 4000 ppm [295/337mg/kg/day

M/F] based on decreased pup weight

in F1a litters

Repro NOAEL = 450 ppm (35/42 mg/kg/day)

Repro LOAEL = 4000 ppm [295/337 mg/kg/day , M/F)

870.4100 [83-1(b)]

1-Year Oral (capsule) 

Study - Dog

42447001 (1992)

0, 0.75, 2.4, 40 mg/kg/day 

Systemic NOAEL = 2.4 mg/kg/day

Systemic LOAEL = 40 mg/kg/day, based on 

increased frequency of abnormal stool, decreased 

body weights and body weight gains, and on 
Page 47 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

Acceptable/Guideline decreased erythrocytes and hemoglobin and 

increased thrombocytes in males. 

870.4300 [83-5(a)]

24- Month Chronic 

Toxicity/ Carcinogenicity 

Study - Rat

00162457 (1985), 00162458 

(1985)

0, 200, 800, or 3200 ppm

M: 0, 10, 40, and 169 mg/kg/day

F: 0, 13, 53, and 219 mg/kg/day

Unacceptable/guideline

NOAEL = 800 ppm (40/53 mg/kg/day M/F).

LOAEL = 3200 ppm (169/219 mg/kg/day M/F) based 

At the doses tested, the carcinogenic potential of 

trifluralin was negative. Dosing was considered 

adequate, based on the differences in body weight 

and body weight gain. 

870.4300 [83-2(a)]

24- Month 

Carcinogenicity Study -

Mouse

00158935 (1986), 40392313 

(1987)

0, 50, 200, or 800 ppm

M: 0, 7.5, 29, and 118 mg/kg/day

F: 0, 10.5, 41, and 165 mg/kg/day

Unacceptable/guideline

Systemic NOAEL = 800 ppm (118/165 mg/kg/day 

in males/females)

Systemic LOAEL = Not achieved 

At the doses tested, the carcinogenic potential of 

trifluralin was negative. Dosing was considered 

inadequate as a toxic effect was not observed, and 

the limit dose was not tested. The LOAEL was not 

observed and the range-finding study indicated that 

dosing was adequate. The NOAEL for the range 

finder was 2500 ppm (equivalent to 375 

mg/kg/day), the highest dose tested.

870.5100

Bacterial reverse gene 

mutation assay

MRID 00148345 (1984) 

Acceptable/Guideline

Trifluralin was tested up to the limit of solubility 

(400 μg/plate -S9; 800 μg/plate +S9). No 

cytotoxicity was observed in any strain at up to 800 

(+S9) or 400 (-S9) μg/plate. No treatment-related 

increases in revertant colonies were observed at any 

dose in any strain (±S9). The positive controls 

induced the appropriate responses. There was no 

evidence of induced mutant colonies over 

background
Page 48 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.5100

Bacterial reverse gene 

mutation assay

MRID 40334707 (1987)

Acceptable/Guideline

In a reverse gene mutation assay in bacteria (MRID 

40334707), Salmonella typhimurium strains TA98, 

TA100, TA1535, TA1537, and TA1538 were 

exposed to trifluralin (96.8% a.i., Lot/Batch #: 

335/336) in dimethyl sulfoxide (DMSO) at 

concentrations of 30, 100, 300, 1000, 3000, or 

10,000 μg/plate in the presence and absence of 

mammalian metabolic activation (S9). The 

standard plate incorporation method was used. 

Standard strain-specific mutagens served as 

positive controls.

Trifluralin was tested up to the limit of solubility 

(3000 μg/plate, +/-S9). No cytotoxicity was 

observed in any strain at up to 3000 μg/plate (+/-

S9). No treatment-related increases in revertant 

colonies were observed at any dose in any strain 

(+/-S9). The positive controls induced the 

appropriate responses. There was no evidence of 

induced mutant colonies over background.

870.5100

Bacterial reverse gene 

mutation assay

MRID 00153173 (1979) 

Acceptable/Guideline

In a reverse gene mutation assay in bacteria (MRID 

00153173), Salmonella typhimurium strains TA98, 

TA100, TA1535, TA1537, and TA1538 were 

exposed to HOE 38474 (trifluralin; purity not 

reported; Lot/Batch #: OH AT204) in DMSO at 

concentrations of 0, 4, 20, 100, 500, 2500, or 

10,000 μg/plate (+/-S9). Standard strain-specific 

positive controls were used.

HOE 38474 was tested up to the limit dose (10,000 

μg/plate, +/-S9). No treatment-related increases in 

revertant colonies were observed at any dose in any

strain (±S9). The positive controls induced the 

appropriate responses. There was no evidence of 

induced mutant colonies over background.

870.5250

Gene Mutation Assay -

Yeast

MRID 00151898 ((1982)

Acceptable/Guideline

The test material was tested up to the limit of 

solubility (1000 mg/L); however, no solubility data 

were provided. No treatment-related increases in 

mutation frequency were observed at any dose with 

or without S9-activation. The positive controls 

induced the appropriate response. There was no 

concentration-related positive response of 

induced mutant colonies over background.
Page 49 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.5300

In vitro mammalian cell 

gene mutation assay

MRID 00126661

Acceptable/Guideline

In a mammalian cell gene mutation assay at the 

thymidine kinase (TK) locus, mouse lymphoma 

L5178Y cells cultured in vitro were exposed to 

trifluralin (95.0% a.i.; Lot/Batch #: 00554AP2) in 

DMSO for 4 hours at 8 concentrations ranging from 

0.5 to 20 μg/mL (individual doses not reported) 

both in the presence and absence of S9-activation. 

Trifluralin was tested up to cytotoxic 

concentrations (20 μg/mL, +/-S9). No treatmentrelated increases in mutation frequency were 

observed at any dose compared to controls. The 

positive controls induced the appropriate response. 

There was no concentration-related positive 

response of induced mutant colonies over 

background.

870.5300

Mammalian Cell Forward 

Gene Mutation Assay

MRID 40765601 (1988)

Acceptable/Guideline

In a mammalian cell gene mutation assay at the 

HGPRT locus (MRID 40765601), Chinese hamster 

ovary (CHO) cells cultured in vitro were exposed to 

trifluralin (97.6% a.i.; Lot/Batch #: 39) in dimethyl 

sulfoxide for 4 hours at concentrations of 50, 100, 

150, 200, 300, 400, or 500 μg/mL (Trial 1, -S9); 50, 

100, 200, 300, 500, 600, or 700 μg/mL (Trial 2, -

S9); 50, 100, 200, 250, 300, 400, or 500 μg/mL 

(Trial 1, +S9); and 50, 100, 200, 300, 400, 500, or 

600 μg/mL (Trial 2, +S9).

Trifluralin was tested up to cytotoxic 

concentrations (>=200 μg/mL, +/-S9) and the limit 

of solubility (>=100 μg/mL, +/-S9). No treatmentrelated increases in mutant frequency were 

observed in either trial in the presence or absence of 

S9. The positive controls induced the appropriate 

response. There was no evidence of induced 

mutant colonies over background in the 

presence or absence of S9-activation.
Page 50 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.5300

Mammalian Cell Forward 

Gene Mutation Assay

MRID 00148318 (1984)

Acceptable/Guideline

In a mammalian cell gene mutation assay at the 

HGPRT locus (MRID 00148318), Chinese hamster 

ovary (CHO) cells cultured in vitro were exposed to 

triflurex technical (trifluralin; purity not reported; 

Lot/Batch #: not reported) in ethanol for 4 hours at 

concentrations of 10, 50, 100, 200, 300, 400, or 500 

μg/mL (-S9) and 50, 100, 200, 300, 400, 500, or 

600 μg/mL (+S9).

Triflurex technical was tested up to cytotoxic 

concentrations (>=200 μg/mL, -S9 and >=300 

μg/mL, +S9) and the limit of solubility (>=100 

μg/mL, +/-S9). No treatment-related increases in 

mutant frequency were observed in either trial in 

the presence or absence of S9. The positive 

controls induced the appropriate response. There 

was no evidence of induced mutant colonies over 

background in the presence or absence of S9-

activation.

870.5385

In Vivo Mammalian 

Cytogenetics [Bone 

Marrow/Spermatogonial 

Aberration Test]

MRID 40765603 (1988)

Acceptable/Guideline

In a bone marrow/spermatogonial chromosome 

aberration assay (MRID 40765603), ICR mice (10 

males/dose, spermatogonial tissue; and 5/sex/dose, 

bone marrow) were dosed once daily via gavage 

(10 mL/kg) with trifluralin (97.6% a.i., Lot/Batch 

No 39) in corn oil at doses of 0, 62.5, 208, or 625 

mg/kg for 5 consecutive days. Bone marrow and 

spermatogonial cells were harvested at 4.5 hours 

after the last treatment. 

Mortalities were observed in the 625 mg/kg females 

(2/5 treated vs. 1/5 controls), and at 62.5 mg/kg in 

the males (2/10 treated vs. 1/10 controls) and 

females (2/5 treated vs. 1/5 controls). Clinical 

signs of toxicity (lethargy, swollen neck, and 

yellow stains around the mouth and perianal area) 

were also observed at >=62.5 mg/kg. No 

statistically significant increases in the percent of 

aberrant cells were observed at any dose in either 

sex in the bone marrow assay or in the males in the 

spermatogonial assay. Trifluralin was tested at an 

adequate dose based on mortalities observed at 

>=62.5 mg/kg. The positive control induced the 

appropriate response. There was no evidence of 

chromosome aberration induced over 

background
Page 51 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.5385

In Vivo Mammalian 

Cytogenetics [Bone 

Marrow Chromosome 

Aberration Test]

MRID 00148320

Acceptable/Guideline

In a bone marrow chromosome aberration assay 

(MRID 00148320), 5 Sprague-Dawley (HSD:([SD] 

BR) rats/sex/dose/sacrifice time were treated once 

via oral gavage with Triflurex technical (trifluralin; 

97.3% a.i.; Batch #: 5320), in corn oil at doses of 0, 

500, 1650, or 5000 mg/kg. Bone marrow cells 

were harvested at 6, 24, or 48 hours after treatment.

Mortality was observed at 1650 (3/15 males and 

5/15 females) and 5000 (2/15 males and 1/15 

females) mg/kg upon initial dosing; however, these 

animals were replaced and only one replacement 

1650 mg/kg female in the 48 hour group died after 

dosing. Triflurex technical induced minimal bone 

marrow toxicity (as indicated by decreased mitotic 

index) at 500 mg/kg in males and 1650 mg/kg in 

females. Dosing was considered adequate based on 

bone marrow toxicity and that the animals were 

dosed above the limit dose (2000 mg/kg). No 

statistically significant increases in the percent of 

aberrant cells were observed at any dose or 

sampling time compared to concurrent controls. 

The positive control induced the appropriate 

response. There was no evidence of chromosome 

aberration induced over background.

870.5395

In vivo Mouse 

Erythrocyte Micronucleus 

assay

MRID 00151895 (1981)

Acceptable/Guideline

In a bone marrow micronucleus assay, 5 NMRI 

mice/sex/dose were treated via oral gavage with 

HOE 38474 (Trifluralin; 98.3% a.i., Lot/Batch #: 

OH AT208), in sesame oil at doses of 0, 25, 250, or 

2500 mg/kg on two consecutive days (24 hours 

apart). Bone marrow cells were harvested at 6 

hours after the last treatment.

No unscheduled deaths occurred during the study. 

No clinical signs of toxicity were observed. No 

statistically significant differences in the number of 

micronucleated polychromatic erythrocytes 

(MPCE) or normocytes and no decrease in 

polychromatic erythrocyte to normocyte 

(PCE:NCE) ratios were noted in the treated animals 

compared to controls; however, only individual 

data were provided. Additionally, although no 

evidence of cytotoxicity (decreased PCE: NCE) 

was noted in the bone marrow, the animals were 

sufficiently dosed (the limit dose was given twice). 

The test material was absorbed as indicated by the 

presence of orange urine in the 2500- mg/kg 
Page 52 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

animals. The positive control induced the 

appropriate response. There was no significant 

increase in the frequency of micronucleated 

polychromatic erythrocytes in bone marrow 

compared to controls.

870.5450

Dominant Lethal - Rat 

MRID 00148319 (1984)

Acceptable/Guideline

In a dominant lethal assay (MRID 00148319), 

groups of 20 male Sprague-Dawley (CD) rats/dose 

were treated once daily via gavage (1.0 mL/dose) 

with Triflurex technical (trifluralin; 97.3% a.i.; 

Batch #: 5320), in corn oil for 5 consecutive days at 

doses of 0, 100, 333, or 1000 mg/kg/day (total 

doses of 0, 500, 1665, or 5000 mg/kg). Beginning 

two days after the last exposure, each male was 

mated sequentially to two untreated female rats per 

week for seven weeks. At 14 days after the 

midpoint of each mating week, the females were 

killed, determined to be pregnant or not pregnant, 

and the number of corpora lutea, living, dead, and 

total implantations was determined. On the fifth 

day of dosing, the positive control males were 

given a single dose of triethylenemelamine (TEM; 

0.3 mg/kg, i.p. in 0.9% saline).

One 1000 mg/kg male (#8476) was found dead 72 

hours after the last treatment. Triflurex technical 

was tested at the limit dose (5000 mg/kg = 1000 

mg/kg/day X 5 days). There were no treatmentrelated effects on fertility, number of implants, preimplantation losses, number of dead implants, 

number of females with 1 or 2 dead implants, or 

ratio of dead implants to total implants at any dose 

in the study. The positive control induced the 

appropriate response. There was no time-related 

positive response of increased pre- or postimplantation loss compared to controls.
Page 53 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.5450

Dominant Lethal -

Mouse

MRID 00151896 (1984)

Acceptable/Guideline

In a dominant lethal assay (MRID 00151896), 30 

male NMRI mice were dosed once daily for 5 

consecutive days via oral gavage (5 mL/kg) with 

HOE 38474 (trifluralin; 98.3% a.i.; Lot/Batch #: 

OHZD99002), in sesame oil at concentrations of 0, 

10, 100, or 1000 mg/kg. After the final treatment, 

each male was mated with 13 untreated females 

during separate 4-day intervals over a 52 day 

period.

No treatment-related mortalities were noted during 

the study. No treatment-related effects on clinical 

signs, body weight, fertilization rate, and pre- or 

post-implantation loss were observed; however, no 

data were provided. The positive control 

(cyclophosphamide) increased the number of postimplantation fetal losses. There was no timerelated positive response of increased pre- or 

post-implantation loss compared to controls.

870.5550

Unscheduled DNA 

synthesis in mammalian 

cell culture

MRID 40765602 (1988)

Acceptable/Guideline

In an unscheduled DNA synthesis assay (MRID 

40765602), primary rat hepatocyte cultures were 

exposed to trifluralin (97.6% a.i.; Lot/Batch #: 39) 

in DMSO for 18-19 hours at concentrations of 0, 

0.032, 0.214, 0.404, 0.917, 2.22, 4.36, 8.52, 21.3, 

42.9, 88.0, 448, or 898 μg/mL. Fifteen doses 

ranging from 0.032-898 μg/mL were used in each 

assay; however, the three doses between 0.032 and 

0.214 μg/mL were not reported.

Trifluralin was tested up to cytotoxic levels 

(determined by trypan blue exclusion), 88.0 μg/mL 

in rat #1 and 42.9 μg/mL in rat #2. There were no 

marked increases observed in the mean NNG or 

percent cells in repair at any dose in either trial. 

The positive controls induced marked increases in 

mean NNG and the percent of cells in repair. 

There was no evidence that unscheduled DNA 

synthesis, as determined by radioactive tracer 

procedures (nuclear silver grain counts), was 

induced.
Page 54 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

870.5550

Unscheduled DNA 

synthesis in mammalian 

cell culture

MRID 00151894 (1982)

Acceptable/Guideline

In an unscheduled DNA synthesis assay (MRID 

00151894), HeLa cell cultures were exposed to 

HOE 38474 (trifluralin, 98.3% a.i.; Lot/Batch #: 

OH AT 208) in DMSO for 1 hour at concentrations 

of 0, 50, 100 or 500 μg/mL both in the presence and 

absence of S9-activation.

HOE 38474 was tested up to cytotoxic 

concentrations (>= 50 μg/mL, +/-S9). No 

statistically significant increases in mean counts per 

minute of the test material with hydroxyurea were 

noted compared to concurrent solvent controls at 

any dose level, either in the presence or absence of 

S9-activation. The positive controls induced the 

appropriate response. There was no evidence that 

unscheduled DNA synthesis, as determined by 

liquid scintillation counting procedures, was 

induced.

870.5900

In vivo Sister Chromatid 

Exchange (SCE) Assay

MRID 00133426 (1983)

Acceptable/Guideline

In a mammalian cell cytogenetics assay [SCE 

induction] using the BrdU tablet method , groups of 

3 female Chinese hamsters/dose were exposed once 

via gavage (10 mL/kg) to trifluralin (95.0% a.i., 

Lot/batch No 00554AP2) in DMSO and 10% acacia 

at concentrations of 200, 300, 400, or 500 mg/kg at 

5 hours following BrdU tablet implantation. Bone 

marrow was collected at 21 hours after treatment.

Trifluralin was tested up to cytotoxic 

concentrations (>=400 mg/kg). Cytotoxicity (as 

indicated by an increase in the number of first 

division metaphase figures) was observed in all 

animals at >=400 mg/kg. No statistically 

significant increases in SCE frequency were 

observed at any dose compared to controls. The 

positive control induced the appropriate response. 

There was no evidence of SCE induced over 

background

870.7845 (85-1)

Metabolism - Rat

Urinary metabolites

41218901 (1989) 

Acceptable/Guideline

There was no sex-dependent effect on metabolic 

profiles. A minimum of 20-30 non-conjugated 

metabolites and an additional 10-20 conjugated 

metabolites were present in the urine, but no parent 

compound was detected. Information on the 

percentage of the administered dose excreted in the 

urine was not provided. However, no single 

metabolite accounted for more than 8-10% of the 

total urinary radioactivity, and the majority of the 
Page 55 of 56

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Trifluralin

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Comments

metabolites were present at 1-2% of the total 

urinary radioactivity. Thus, almost all of the 

metabolites were minor (<5% of the total 

radioactive dose). Metabolite F1B was found at 

8.2-8.9% of the total urinary radioactivity in both 

sexes, and Metabolite F2, N-[(3-(acetylamino)-2-

amino-5-(trifluoromethyl)phenyl] acetamide, was 

found at 4.0-5.2%. Metabolite F1B was partially 

characterized as retaining the trifluoromethyl 

groups, the two equivalent aromatic protons, and 

the two nitro groups, but the propyl groups were 

lost. Ten other metabolites were identified (<0.1-

3.7% of total urinary radioactivity, each compound 

in each sex). Two additional metabolites were 

partially characterized (0.1-2.6% of total urinary 

radioactivity, each compound in each sex).

Four metabolic pathways were identified as 

follows: (i) oxidative N-dealkylation of one or both 

propyl groups and metabolites which were 

hydroxylated on the propyl side chain; (ii) 

reduction of one or both nitro groups to the 

corresponding amine; (iii) cyclization reactions to 

give a variety of substituted and unsubstituted 

benzimidazole metabolites; and (iv) conjugation 

reactions, including acetylation of the reduced nitro 

groups, sulfate, and glucuronic acid conjugates.

Special study

3-Mo Feeding - Rat with

Urinalysis study

00157156 (1985), 40138301(1986)

41086101 (1989)

0, 50, 200, 800, 3200, and 6400 

ppm

0, 2.6, 10.7, 42.2, 170.2, and 342.1 

mg/kg/day

Acceptable/Nonguideline

NOAEL = 200 ppm (10.7 mg/kg/day)

LOAEL for nephrotoxicity = 800 ppm (42.2

mg/kg/day), based on the presence of cortical 

tubular cytoplasmic hyaline droplets; increased 

total protein, AST, and LDH in the urine; and 

increased urinary volume upon protein 

electrophoresis and urinalysis.
Trifluralin Human Health Risk Assessment DP No. D401005

Page 56 of 56