Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 2 of 57

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

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

2.1 Data Deficiencies ............................................................................................................. 7

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

2.2.1 Enforcement Analytical Method .................................................................................. 7

2.2.2 Established Tolerances................................................................................................. 8

2.2.3 International Harmonization......................................................................................... 8

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

2.3.1 Recommendations from Occupational Assessment ..................................................... 8

3.0 Introduction.......................................................................................................................... 8

3.1 Chemical Identity and Physical/Chemical Characteristics............................................... 8

3.2 Pesticide Use Pattern........................................................................................................ 9

3.3 Anticipated Exposure Pathways..................................................................................... 12

3.4 Consideration of Environmental Justice ........................................................................ 12

3.5 Incident Reports ............................................................................................................. 12

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

4.1 Toxicology Studies Available for Analysis ................................................................... 13

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)................................... 13

4.3 Toxicological Effects ..................................................................................................... 14

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 14

4.4.1 Completeness of the Toxicology Database ................................................................ 14

4.4.2 Evidence of Neurotoxicity.......................................................................................... 15

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal............. 15

4.4.4 Residual Uncertainty in the Exposure Database......................................................... 15

4.5 Toxicity Endpoint and Point of Departure Selections.................................................... 15

4.5.1 Dose-Response Assessment ....................................................................................... 15

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ........... 17

4.5.3 Cancer Classification and Risk Assessment Recommendation.................................. 17

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

Assessment................................................................................................................................ 18

 4.6 Endocrine Disruption.................................................................................................. 19

5.0 Dietary Exposure and Risk Assessment ............................................................................ 19

5.1 Summary of Plant and Animal Metabolism Studies...................................................... 19

5.1.1 Summary of Environmental Degradation................................................................... 20

5.1.2 Residues of Concern Summary and Rationale ........................................................... 20

5.2 Food Residue Profile...................................................................................................... 21

5.3 Water Residue Profile .................................................................................................... 21

5.4 Dietary Risk Assessment................................................................................................ 22

5.4.1 Description of Residue Data Used in Dietary Assessment......................................... 22

5.4.2 Percent Crop Treated Used in Dietary Assessment.................................................... 22

5.4.3 Acute Dietary Risk Assessment ................................................................................. 22

5.4.4 Chronic Dietary Risk Assessment .............................................................................. 22

5.4.5 Summary Table........................................................................................................... 22

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 23

6.1 Residential Bystander Post-application Inhalation Exposure ........................................ 23
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 3 of 57

6.2 Spray Drift...................................................................................................................... 23

6.2.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications......... 25

7.0 Aggregate Exposure/Risk Characterization ................................................................... 26

8.0 Cumulative Exposure/Risk Characterization ................................................................. 26

9.0 Occupational Exposure/Risk Characterization............................................................... 26

9.1 Short-/Intermediate Handler Risk .................................................................................. 26

9.2 Short-/Intermediate-term Post-Application Risk ........................................................... 28

9.2.1 Dermal Post-application Risk..................................................................................... 28

9.2.2 Inhalation Post-application Risk................................................................................. 29

10.0 References.......................................................................................................................... 30

Appendix A. Toxicology Profile and Executive Summaries....................................................... 32

A.1 Toxicology Data Requirements...................................................................................... 32

A.3 Hazard Identification and Endpoint Selection ............................................................... 35

A.4 Executive Summaries..................................................................................................... 37

Appendix B. Physical/Chemical Properties................................................................................. 47

Appendix C. Residue Summary Table......................................................................................... 50

Appendix D. Spray Drift Estimate Tables................................................................................... 51

Appendix E. Occupational Exposures and Risk Estimates Table................................................ 53
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 4 of 57

1.0 Executive Summary

Introduction

The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. The HED Tebuthiuron

Registration Review Team has evaluated the current databases to support the Registration 

Review of the active ingredient (ai), tebuthiuron. Tebuthiuron is a relatively nonselective

substituted urea herbicide that acts by inhibiting photosynthesis. It is used to control broadleaf, 

grassy weeds, and woody plants. Use sites include pastureland, rangeland, and a variety of nonfood sites including airports/landing fields, outdoor industrial areas, non-agricultural rights-ofway, fencerows, hedgerows, uncultivated areas/soils, and under paved roads and sidewalks in 

areas where no future landscaping is planned. Tebuthiuron is not registered for agricultural 

crops or for residential use. End use products are formulated as dry flowable (DF), water 

dispersible granulars (WDG), pellets (P), and granulars (G). Applications are conducted by 

aerial, ground, and handheld equipment. 

Updated points of departure (POD) and safety factors (SF) were used for the dietary and 

occupational exposure risk assessments, as well as for the spray drift assessment. No changes to 

the current tolerances for meat and milk are recommended at this time. Tebuthiuron is not 

registered for residential uses; however residential bystander exposure may be possible through 

spray drift. Therefore, HED has conducted a spray drift assessment and there are risks of 

concern identified from exposures to both adults (dermal only) and children 1 to < 2 years old 

(dermal and incidental oral). There are no dietary (food and drinking water) or aggregate risks of 

concern associated with tebuthiuron. There are several occupational dermal and inhalation risks 

of concern for scenarios including mixing/loading for aerial application, and ground application,

and mixing/loading/applying using handheld equipment. 

Hazard Identification

The most consistent toxicological effect across the tebuthiuron database is decreased body 

weight, occurring in rats, rabbits and dogs. No evidence of reproductive, neurological or 

immunological toxicity were identified in the database. No evidence of qualitative/quantitative 

susceptibility was observed in the rabbit or rat database. Decreased fetal body weights and 

increased number of litters with early resorptions in the rabbit developmental study were 

observed at the same dose. In rats, decreases in pup body weights were observed on post natal 

day (PND) 21 in the first and second (F1 and F2) generation pups occurred in the presence of 

maternal toxicity (decreases in F1female adult bodyweights).

The acute toxicity studies indicate that tebuthiuron is more toxic following oral (Toxicity 

Category II) exposure than either dermal (Toxicity Category IV) or inhalation (Toxicity 

Category III) exposure. Tebuthiuron is not an eye or skin irritant and not a skin sensitizer. In the 

2002 Preliminary Human Health Risk Assessment (P. Deschamp, D274580, April 22, 2002)

tebuthiuron was classified as a Group D compound “not classifiable as to human 

carcinogenicity.”

Dose Response Assessment
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 5 of 57

Acute Dietary

No appropriate acute toxicological endpoint attributable to a single exposure was identified for 

the general population. An acute reference dose (aRfD) was selected for females 13 – 49 years 

old based on an increase in early resorptions at the lowest observed adverse effect level 

(LOAEL) of 25 mg/kg/day in the developmental toxicity study in rabbits with a no adverse effect 

level (NOAEL) of 10 mg/kg/day. 

Chronic Dietary

The chronic reference dose (cRfD) was selected from the 2-generation reproductive toxicity 

study in rats based on decreased body weights in parents and pups at the LOAEL of 26

mg/kg/day. The study NOAEL was 14 mg/kg/day.

Non-Dietary Endpoints for Occupational and Spray Drift Analysis

Incidental Oral

The 2-generation reproductive toxicity study in rats was selected with a NOAEL of 14 

mg/kg/day for the short-term (1-30 days) incidental oral endpoint. The LOAEL is 26 mg/kg/day 

based on decreased body weights in F1 females and decreased pup body weights on PND 21 in 

the F1 and F2 generation.

Dermal and Inhalation

A dermal toxicity study is available for tebuthiuron, however, the short- and intermediate-term 

dermal endpoints were selected from the 2-generation reproductive toxicity study in rats because

the dermal study conducted is not protective of the adverse outcome (resorptions) of concern for 

pregnant females. Since the endpoint is derived from an oral study, HED would typically apply 

a dermal absorption factor, however because no dermal absorption data are available and the 

physical properties of the chemical support the potential for dermal absorption this risk 

assessment assumes 100% dermal absorption for tebuthiuron. There are no route-specific 

inhalation studies available for tebuthiuron. The Hazard and Science Policy Council, 

(HASPOC) determined that a guideline 90-day inhalation study is required for this route of 

exposure. In the absence of an inhalation study, HED has selected short- and intermediate-term 

endpoints from the 2-generation rat study discussed above and has retained an additional 10X 

database uncertainty factor for the inhalation risk assessments to account for the missing data. 

Long-term exposures are not anticipated from the occupational use of tebuthiuron. 

Uncertainty/Safety Factors

For acute and chronic dietary, incidental oral, and dermal risk assessments, a 100X uncertainty 

factor is applied (interspecies factor of 10X and intraspecies factor of 10X). Acute and chronic 

risk estimates are expressed as a percent of the population adjusted dose (PAD) and risks which 

do not exceed 100% of the acute PAD (aPAD) or chronic PAD (cPAD) are not of concern. 

Incidental oral or dermal risk estimates resulting in MOEs greater than or equal to 100 do not 

exceed HED’s level of concern (LOC). 

The total uncertainty/safety factor for the inhalation risk assessments is 1000 and includes a 10X 

for interspecies extrapolation, 10X for intraspecies variation, and a 10X database uncertainty 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 6 of 57

factor to account for the missing inhalation study. Inhalation risk estimates resulting in MOEs 

greater than or equal to 1000 are not of concern. 

There is no evidence of increased qualitative or quantitative susceptibility in the rat 2-generation 

reproduction study or the rat and rabbit developmental studies. Furthermore, there is no 

evidence of neurotoxicity in any of the submitted studies for tebuthiuron and there is no residual 

uncertainty in the exposure database. Therefore, the FQPA safety factor (for the protection of 

infants and children) was reduced to 1X. 

Residue Chemistry Considerations

There are no outstanding residue chemistry data requirements for tebuthiuron. The nature and 

magnitude of the residue are well understood and adequate analytical methods exist to support 

the existing tolerances. No changes to existing tolerances are required. There are no 

harmonization issues associated with tebuthiuron.

Exposure/Risk Assessment and Risk Characterization

Dietary Risk Assessment

Since there are no direct applications to agricultural crops, the only source of food exposure is 

the potential consumption of secondary residues in meat and milk from livestock fed 

tebuthiuron-treated grass forage and hay. Additionally, the potential exists for dietary exposure 

via the consumption of drinking water. Acute and chronic dietary risk assessments were

conducted for tebuthiuron which included tolerance level residues in animal commodities, and 

modelled estimates of drinking water concentrations, (EDWC) provided by the Environmental 

Fate and Effects Division, (EFED). However, since water was the risk driver, a time series water 

distribution was used. Percent crop treated information were not relevant to these assessments. 

The partially refined acute estimated dietary risk for females 13-49 years old is not of concern; 

the dietary risk is 93% of the aPAD at the 95th percentile. The chronic estimated dietary risks are 

not of concern; the dietary risk for the general U.S. population is 30% of the cPAD and for the 

highest exposed population subgroup (all infants) is 72% of the cPAD. HED is concerned when 

the estimated dietary risk exceeds 100% of the PAD.

Residential Exposure and Risk Assessment

Residential exposure was not assessed as there are no residential uses for tebuthiuron. 

Spray Drift Assessment

A non-occupational spray drift assessment has been conducted for tebuthiuron based on the 

highest rate currently registered for aerial application on pastureland/rangeland and general noncropland (6 lbs. ai/acre). Spray drift occurs from the movement of tebuthiuron away from 

rangeland/pastureland application sites. The dermal and incidental oral risk estimates calculated 

for adults and children ages 1 to <2 years old were combined since the toxicological effects for 

these exposure routes were similar. The total applicable LOC is 100, so MOEs less than 100 

represent risk estimates of concern. Adult dermal risk estimates and children’s combined dermal 

and incidental oral risk estimates from indirect exposure to tebuthiuron related to spray drift 

indicate that exposure above the LOC could occur at distances from 0 feet to greater than 150
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 7 of 57

feet depending on the nozzle type, droplet size, and application equipment.

Occupational Handler and Post Application Exposure and Risk Assessments

Occupational handler risks were assessed for the dermal and inhalation routes of exposure. 

Since toxic effects are similar from the dermal and inhalation routes of exposure, but the LOC 

values for dermal exposure (100) and inhalation exposure (1000) are different, a total aggregated 

risk index (ARI) was used to estimate combined estimated handler risks. The LOC ARI is 1; 

therefore, ARIs of less than 1 are potentially of concern to the Agency. Several of the

occupational handler scenarios resulted in ARIs < 1 with the personal protective equipment 

(PPE) currently required on the label and remain a concern despite consideration of possible 

mitigation methods such as requiring doubler layer dermal PPE, respirators, and engineering 

controls.

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

exposure assessment was not performed for tebuthiuron at this time. 

Use of Human Studies

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

intentionally exposed to a pesticide or other chemicals. These data, which include the Pesticide 

Handlers Exposure Database Version 1.1 (PHED 1.1) and the Agricultural Handler Exposure 

Task Force (AHETF) database, are subject to ethics review pursuant to 40 CFR 26, have 

received that review, and are compliant with applicable ethics requirements. Certain studies 

within this assessment may have included reviews by the Human Studies Review Board.

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

human health risk assessment.

2.0 HED Recommendations

2.1 Data Deficiencies

HED’s Hazard and Science Policy Council (HASPOC) determined that a guideline 90-day

inhalation study is required. (J. Leshin, TXR 0056925, May 27, 2014). No other toxicology 

studies are required to support the registration review of tebuthiuron.

There are no residue chemistry or occupational/residential exposure data gaps for tebuthiuron.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate analytical method is available for the enforcement of plant and animal commodity 

tolerances established for tebuthiuron. A gas-liquid chromatography (GLC) method with flame 

photometric detection is designated as Method II in PAM Vol. II. Tebuthiuron and regulated 

metabolites 104 and 109 are thermally degraded on the GLC column and are determined as 5-(1,

1-dimethylethyl)-N-methyl-1,3,4-thiadiazol-2-amine; metabolite 103 (OH) is determined as 5-(2-
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 8 of 57

hydroxy-1,1-dimethylethyl)-N-methyl-1,3,4-thiadiazol-2-amine. The stated detection limits are 

0.1 ppm for tebuthiuron and metabolites 104 and 109, and 0.2 ppm for metabolite 103(OH). The 

structures of these metabolites are shown in Appendix B Table B.4: Figure A. 

2.2.2 Established Tolerances

Tolerances are established for the herbicide tebuthiuron under 40 CFR: §180.390; for Grass, 

(forage and hay) –10 ppm; Cattle, (fat and meat) –1.0 ppm; Goat (fat and meat) –1.0 ppm; Horse, 

(fat and meat) – 1.0 ppm; Sheep (fat and meat) –1.0 ppm; Cattle, Goat, Horse and Sheep, meat 

(byproducts) – 5.0 ppm and milk at 0.8 ppm. These tolerances are adequate to support the 

currently established uses of tebuthiuron. 

2.2.3 International Harmonization

There are no Codex, Canadian, or Mexican Maximum Residue Limits (MRLs) established for 

tebuthiuron; therefore issues of harmonization are not relevant to this risk assessment The 

International Residue Limit (IRL) Status sheet is attached as Appendix C . 

2.3 Label Recommendations

2.3.1 Recommendations from Occupational Assessment

HED recommends PRD ensure that that worker protection standard (WPS) language appears on 

all registered labels. Also if pastureland is intended for haying harvest, a re-entry interval (REI) 

of 12 hours based on the acute toxicity must be on the labels to protect workers from postapplication exposures. 

HED notes that the occupational assessment resulted in dermal and inhalation risk estimates of 

concern for several exposures scenarios (presented in section 9.1) with the current PPE on labels. 

3.0 Introduction

Tebuthiuron is a relatively nonselective substituted urea herbicide that acts by inhibiting 

photosynthesis. It is used to control broadleaf, grassy weeds, and woody plants. Use sites 

include pastureland, rangeland, and a variety of non-food sites and uncultivated areas/soils.

Tebuthiuron is not registered for agricultural crops or for residential use. The only source of 

dietary (food) exposure is the consumption of secondary residues in meat and milk from 

livestock fed tebuthiuron-treated grass forage and hay. Tebuthiuron primary environmental 

properties affect drinking water sources. The chemical is resistant to biological and chemical 

degradation, and its principle route of dissipation in the environment appears to be off-site 

transport. Because of tebuthiuron’s environmental persistence and low adsorption to soil it can 

be transported to ground water through leaching and to surface water through run-off and offtarget spray drift. 

3.1 Chemical Identity and Physical/Chemical Characteristics
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 9 of 57

Tebuthiuron is a solid at room temperature. Any losses due to volatilization/sublimation are 

expected to be minimal due to the vapor pressure (2 x 10-6 mm Hg at 25 °C). Tebuthiuron is 

stable to anaerobic soil metabolism and is likely to persist in an anaerobic soil environment. See 

Table 3.1 and Appendix B for a summary of tebuthiuron nomenclature and physical/chemical 

properties.

Table 3.1- Tebuthiuron Nomenclature

Chemical structure

Common Name Tebuthiuron

Empirical Formula C9H16N4OS

IUPAC Name 1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-1,3-dimethylurea

CAS Name Urea, N-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-N,N'-dimethyl

CAS Registry Number 34014-18-1

3.2 Pesticide Use Pattern

Pastureland and rangeland appear to be the dominate use site in the western part of the United 

States (US). The final biological assessment prepared by the Bureau of Land Management in 

2007 estimated the number of public land acres treated with tebuthiuron at an average of 48,000 

from the years 1997 to 2005. In addition, registrant provided information estimating a 

significant amount of tebuthiuron is applied aerially to pastureland/rangeland in western US 

states. While tebuthiuron retreatment intervals (RTI) are once every 2 to 3 years and twice every 

6 years, large agribusiness and/or commercial applicators could apply tebuthiuron over a period 

of weeks for multiple clients within a region. In addition to pastureland/rangeland, tebuthiuron 

can be applied aerially, by ground, and with handheld equipment on general non-crop land, 

wildlife clearings and rights-of-way. Tebuthiuron end-use formulations include dry flowable, 

water dispersible granular, pelleted/tablets, and granules. A summary of the existing use patterns 

for tebuthiuron are shown in Tables 3.2.1 below.
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 10 of 57

Table 3.2.1 Summary of Directions for Use of Tebuthiuron

Company

Formulation 

Name 

EPA Reg. 

No.

% 

a.i

Application Equipment and 

Rate (lb ai/A)

Max. No. 

Application per 

Season

Max. Seasonal 

Application

Rate (lb ai/A)

Use sites Use Directions and Limitations

Dry Flowable

Dow 

AgroSciences 

LLC

Spike 80DF

62719-107

80

Broadcast 

Aerial and

Ground

Handheld for 

Spot 

Treatment 

4 lb ai/A aerial

pastureland, 

and

6 lb ai/A 

ground 

broadcast or 

1.6 lb ai/gallon 

(spot treatment)

1 application 

every year with 

up to 6 lb ai/acre 

in a 6 year 

period. .

4 lb ai/acre per 

year for haying

and 

no more than 

two treatments 

totaling 6 lb 

ai/A every 6 

years

Non-cropland, 

including rangeland, 

permanent grass 

pastures, fencerows, 

and wildlife clearings

PPE includes eye protection, long-sleeved 

shirt, long pants, shoe and socks, and 

chemical resistant gloves. Not registered 

in Florida or Nassau and Suffolk NY. Not 

for use in California. Not for residential 

use. Do not apply on field crops. Aerial by 

helicopter and wing fixed for herbicidal 

firebreaks on rangeland. Aerial 

application limited to helicopter for rightsof-way. 

Alligare

LLC

Tebuthiuron 

80WG

81927-37

Pellet

Dow 

AgroSciences 

LLC

Spike 20P

62719-121 20

Aerial, 

Ground, and 

Handheld for 

Spot 

Treatment

4 lb ai/A aerial

pastureland, 

and 

6 lb ai/A for 

ground 

broadcast and 

spot treatment

1 application /3 

years

4 lb ai/acre per 

year for haying

and 

no more than 

two treatments 

totaling 6 lb 

ai/A every 6 

years

Rights-of Way, 

pastureland, 

rangeland, noncropland, fence rows, 

firebreaks, industrial 

sites, wildlife 

clearings.

No PPE listed. Dormant season 

application. Do not feed to livestock for 1 

year after treatment. Do not apply to soil 

that is frozen. Not used in Nassau and 

Suffolk Counties in NY and restrictions in 

Florida.

Spike 40P

62719-122 40

PPE includes long sleeved shirt and long 

pants, shoes plus socks, waterproof 

gloves, protective eyewear. Dormant 

season application. Do not feed to 

livestock for1 year after treatment. Do not 

apply to soil that is frozen. Not used in 

Nassau and Suffolk Counties in NY and 

restrictions in Florida.

Alligare, LLC

Tebuthiuron 

20P

81927-41

20

No PPE listed. Dormant season 

application. Do not feed to livestock for 1 

year after treatment. Do not apply to 

frozen soil. Not used in Nassau and 

Suffolk Counties in NY restrictions in 

Florida.

Granular

Rainbow 

Technology 

Corporation

Rainbow 

Weed Killer 

4037

13283-18

2

Ground and 

handheld 

spot 

treatment 

6 lb ai/A 

broadcast and 

spot treatment

2 applications 

per year with 

retreatment 

6 lb ai/A every 6 

years

Buried cable 

closures, telephone 

booths, cross-connect 

boxes, transformer 

PPE includes NIOSH filter respirator for 

tractor drawn spreaders, and all loaders.

All handlers must wear long sleeved shirt, 

long pants shoes plus socks, and chemical 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 11 of 57

Table 3.2.1 Summary of Directions for Use of Tebuthiuron

Company

Formulation 

Name 

EPA Reg. 

No.

% 

a.i

Application Equipment and 

Rate (lb ai/A)

Max. No. 

Application per 

Season

Max. Seasonal 

Application

Rate (lb ai/A)

Use sites Use Directions and Limitations

Rainbow 

Weed Killer 

4049

13283-21

1

(0.00015 lb 

ai/ft2)

interval of 90 

days

6 lb ai/Ain a 6 

year period

pads, fire plugs, 

rights-of-way and 

industrial areas.

resistant gloves. Do not uses in any 

recreational areas or in homes. Do not 

apply by air. Do not enter until dust 

settles. Spoon or pump -feed spreader is 

prohibited. Applied anytime except when 

ground is frozen.

SSI Maxim Co. 

Inc.

Sprakil Sk-13

34913-15 1

Sprakil SK-26

34913-16 2

Sprakil SK-13

34913-15 1

Sprakil S-5

34913-10 5

PPE includes long sleeved shirt, long pants 

shoes plus socks, and chemical resistant 

gloves. Do not use on areas such as walks, 

driveways, streets. Not apply on or near 

field crops. 

Technical

Dow 

AgroSciences 

LLC

Spike 

Technical 

Herbicide

62719-109 99 %

Makhteshim 

Agan of North 

America, Inc.

Tebuthiuron 

Technical

83558-33
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 12 of 57

3.3 Anticipated Exposure Pathways

Exposure to tebuthiuron can be expected through food and drinking water. There are no direct 

applications to agricultural crops. The only source of food exposure is the potential for 

consumption of secondary residues in meat and milk from livestock fed tebuthiuron-treated grass 

forage and hay. Dietary exposure can also occur from consumption of drinking water. There are 

no residential uses of tebuthiuron, so exposure in residential or non-occupational settings is not 

likely, however as mentioned previously, a spray drift assessment was conducted to assess for 

possible exposure from contact to deposits on off target sites. In an occupational setting, 

applicators may be exposed while handling the pesticide prior to application, as well as during 

application. Occupational post-application dermal exposure from workers re-entering 

tebuthiuron treated areas is not anticipated because the chemical is a non-selective herbicide used 

in non-agricultural areas. 

3.4 Consideration of Environmental Justice

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

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

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

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

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

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

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

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture under the National Health and Nutrition Examination Survey, What We Eat in 

America, (NHANES/WWEIA). These food consumption patterns 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 children, youths, and adults entering or playing on treated areas 

post-application 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.

3.5 Incident Reports

HED completed a review of tebuthiuron incidents in the OPP Incident Data System (IDS) and 

the Centers for Disease Control and Prevention/National Institute for Occupational Safety and 

Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides 

(SENSOR) databases. Based on the low frequency and severity of incident cases reported for 

tebuthiuron in both IDS and NIOSH SENSOR Pesticides, there does not appear to be a concern 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 13 of 57

at this time that would warrant further investigation (M. Hawkins, Updated Review of 

Tebuthiuron Incident Reports, May 7, 2009). The Agency will continue to monitor the incident 

information and if a concern is triggered, additional analysis will be conducted. The Agricultural 

Health Study (AHS) is also a potential source of information associated with human health 

effects associated with certain pesticides. Tebuthiuron is not included in the AHS.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database for tebuthiuron is not complete but provides sufficient information to 

adequately identify hazards for risk assessment purposes. The database includes the following 

studies:

 90-Day oral toxicity studies in the rat and dog,

 28-Day dermal toxicity in the rabbit,

 Developmental toxicity in the rat and rabbit,

 2-Generation reproductive toxicity in the rat,

 Chronic toxicity in the dog,

 Genetic toxicity battery,

 Metabolism study in the rat, and 

 Immunotoxicity study in the rat. 

The Hazard and Science Policy Council (HASPOC, TXR 0056925 05/27/2014) determined that 

the acute neurotoxicity study and sub-chronic neurotoxicity, chronic/carcinogenicity study in the 

rat, and the carcinogenicity study in the mouse may be waived. A sub-chronic inhalation study 

was required and a route-specific 10x database uncertainty factor has been retained.

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

Tebuthiuron is highly absorbed (84-95%) and rapidly excreted (within 24 hours) following oral 

administration in rats. Following administration of 14C-tebuthiuron, metabolites in the urine 

accounted for up to 97.1% of the dose, and metabolites in the feces accounted for an average of 

3.5% of the administered dose. Biliary excretion studies in rats indicated most of the 

radioactivity eliminated in the feces was absorbed from the gastrointestinal tract and eliminated 

through the bile. The major metabolite in 0-24 hour urine of male (58.3%) and female (62.1%) 

rats was identified as hydroxylated tebuthiuron metabolites (109-OH and /or 104-OH). The 

second most abundant metabolite was identified as metabolite 106 of tebuthiuron. This 

comprised between 9-15% of the administered dose in 0-24 hour urine of low dose rats, and 

between 1-10% of the administered dose in high dose rats. Two other metabolites identified, 

104/109 and 103-OH, comprised between 2-10% of the administered dose in male and female 0-

24 hour urine. No evidence of bioaccumulation was identified. 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 14 of 57

4.3 Toxicological Effects

The most consistent toxicological effect across the mammalian database is decreased body 

weight, occurring in rats, rabbits and dogs. No effects were observed in mice following longterm exposure up to the highest dose tested (240 mg/kg/day). At higher doses in rats, slight 

vacuolization of the pancreatic cells were observed, and in dogs, signs of liver toxicity were 

observed (including increased liver weights and enzyme activity). Toxicity in the 90-day and 

long-term rat and dog studies occurred at similar doses indicating no progression of toxicity over 

time. In a dermal toxicity study, no effects were observed up to the limit dose. Based on the 

available data, no evidence of reproductive, neurological, genotoxic, or immunotoxic effects 

were identified in the database. 

No evidence of qualitative/quantitative susceptibility was observed in the database. In rabbits 

significantly decreased fetal body weights were observed at 25 mg/kg/day. An increase in the 

number of litters with early resorptions was also observed at this dose level. However, as limited 

data are available, and the etiology of the increased resorptions is unknown, this effect is 

considered to reflect toxicity in both the dams and pups. No developmental toxicity was 

observed in rats. In a 2-generation reproductive toxicity study decreases in pup body weights 

were observed on PND 21 in the F1 and F2 generation pups at 26 mg/kg/day. These effects 

occurred in the presence of maternal toxicity (decreases in F1 female adult bodyweights). In 

rats, decreases in pup body weights were observed PND 21 in the first and second (F1 and F2) 

generation pups at 26 mg/kg/day. These effects occurred in the presence of maternal toxicity 

(decreases in F1 female adult bodyweights).

The acute toxicity studies indicate that tebuthiuron is more toxic following oral (Toxicity 

Category II) exposure than either dermal (Toxicity Category IV) or inhalation (Toxicity 

Category III) exposure. This is supported by ADME data, indicating complete and rapid 

absorption of tebuthiuron following oral administration. Tebuthiuron is not an eye or skin irritant 

and not a skin sensitizer.

In the 2002 Preliminary Human Health Risk Assessment, tebuthiuron was classified as a Group 

D compound “not classifiable as to human carcinogenicity.” For more detail on cancer 

classification see Section 4.5.3.

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

HED recommends that the 10X FQPA Safety Factor (for the protection of infants and children) 

be reduced to 1X. No evidence of increased quantitative/qualitative susceptibility was observed.

The effects observed in the rabbit developmental and rat 2-generation reproduction studies occur 

in the presence of maternal toxicity. Nevertheless, these studies have clearly defined 

NOAEL/LOAELs and the selected points of departure (PODs) are protective of all observed 

adverse effects. No clinical signs indicative of neurotoxicity were identified throughout the 

database for tebuthiuron. The dietary and residential bystander assessments are based on reliable 

data and will not underestimate exposure.

4.4.1 Completeness of the Toxicology Database
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 15 of 57

The toxicology database for tebuthiuron is not complete, but provides sufficient information to 

adequately identify hazards for risk assessment purposes. HASPOC (TXR 0056925) decided

based on a weight of evidence determination, that the acute neurotoxicity study and subchronic 

neurotoxicity, chronic/carcinogenicity study in the rat, and the carcinogenicity study in the 

mouse may be waived. The required sub-chronic inhalation study was not waived as the oral 

endpoint results in unacceptable MOEs for workers. Therefore, an additional 10X uncertainty 

factor was retained for the occupational inhalation assessment. 

4.4.2 Evidence of Neurotoxicity

No evidence of neurotoxicity was observed in any of the submitted studies for tebuthiuron. The 

HASPOC determined that the acute and subchronic neurotoxicity studies are not required at this 

time based on the following rationale: 1) the lack of neurotoxicity signs in the available 

toxicology database for tebuthiuron; 2) the primary toxic effect throughout the database is 

decreased bodyweights; and 3) using an oral POD, the acute and chronic dietary exposures (food

and water) for tebuthiuron result in risk estimates of less than 100% and therefore not of concern.

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

The available data do not provide evidence of any increased susceptibility in the offspring in 

either of the rat or rabbit developmental toxicity studies for tebuthiuron, nor in the rat twogeneration reproduction study. 

Decreased fetal body weights and early resorptions were observed in the rabbit developmental 

toxicity study, and decreased post-natal body weights were observed in the rat 2-generation 

toxicity study. Both of these effects occurred in the presence of maternal toxicity. No 

developmental effects were observed occurred in the rat developmental study. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. Since the dietary estimates were 

based on conservative assumptions, HED is confident that the assessments do not underestimate 

dietary (food and water) exposure. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

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

various exposure scenarios is presented in Appendix A and summarized in Table 4.5.4.

For acute dietary assessment of females 13 – 49 years old, the developmental toxicity study in 

rabbits was selected with a NOAEL of 10 mg/kg/day for dams and pups. The LOAEL is 25 

mg/kg/day for dams and pups based on early resorptions and decreased fetal body weights. 

Early resorptions could be from a single exposure during pregnancy and are therefore considered 

a potential acute effect, and therefore, appropriate for the acute dietary endpoint scenario for 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 16 of 57

females of child-bearing age. No appropriate toxicological endpoints attributable to a single 

exposure were identified for the general population. 

For chronic dietary exposure and risk assessment, the 2-generation reproductive toxicity study in 

rats was selected with a NOAEL of 14 mg/kg/day. The LOAEL is 26 mg/kg/day based on 

decreased body weights in F1 parental females (13%) and decreased pup body weights (17%) on 

PND 21 in the F1 and F2 generation (5-8%). The 2-generation reproductive toxicity study was 

selected for the chronic dietary exposure because the endpoint is applicable to the population of 

concern (general population) and the duration of exposure. As the NOAEL/LOAEL values are 

similar between the developmental and 2-generation toxicity studies (10/14 mg/kg and 25/26 

mg/kg, respectively), the 14 mg/kg/day NOAEL represents a smaller dose spread between the 

NOAEL/LOAEL of both studies and the agency is confident that the NOAEL of 14 mg/kg/day is 

protective of both the developmental effects observed in the rabbit and the parental and offspring 

effects in rats.

For short-term incidental oral exposure (1-30 days), the 2-generation reproductive toxicity study 

in rats was selected with a NOAEL of 14 mg/kg/day. The LOAEL is 26 mg/kg/day based on 

decreased body weights in F1 adult females (13%) and decreased pup body weights on PND 21 

in the F1 and F2 generation (5-8%). The endpoint of concern in this study (bodyweight) is 

appropriate for the age of the population (infant and children) and the duration of concern.

Intermediate and long-term incidental oral exposure assessment are not required because these

exposure lengths are not expected based on current use patterns.

For short and intermediate-term dermal exposure, a 28-day rabbit dermal toxicity is available. 

However, the dermal study does not evaluate the endpoint of concern, resorptions. Therefore, 

the 2-generation reproductive toxicity study in rats was selected with a NOAEL of 14 

mg/kg/day. The LOAEL is 26 mg/kg/day based on decreased body weights in F1 females (13%) 

and decreased pup body weights on PND 21 in the F1 and F2 generation (5-8%). A dermal risk 

assessment is being conducted for the following reasons: the dermal toxicity study conducted is 

not protective of the adverse outcome (resorptions) of concern for pregnant females; no dermal 

absorption data are available, and the physical properties of the chemical support the potential 

for dermal absorption (log Kow of 1.8 and a molecular weight of < 500). As discussed above, the 

2-generation reproductive toxicity study with a NOAEL of 14 mg/kg was selected as it is 

protective of both developmental effects in rabbits and offspring effects observed in the rats. 

There is no proposed long-term use; therefore, risk assessment for long-term dermal exposure is 

not required.

For short and intermediate-term inhalation exposure, no route-specific inhalation study is 

available for tebuthiuron. Consequently, the 2-generation reproductive toxicity study with a 

NOAEL of 14 mg/kg was selected for risk assessment, because it is protective of both 

developmental effects in rabbits and offspring effects observed in the rats. There is no proposed 

long-term use; therefore, risk assessment for long-term inhalation exposure is not required.

For acute and chronic dietary, incidental oral and dermal exposures a 100X uncertainty factor is 

applied (interspecies factor of 10X and intraspecies factor of 10X). An additional 10x database 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 17 of 57

uncertainty factor has been applied for inhalation exposure due to the lack of a subchronic 

inhalation study.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

When there are potential occupational and residential exposures to a pesticide, the risk 

assessment must address exposures from three major sources: incidental oral, dermal, and 

inhalation. Oral, dermal, and inhalation routes can be combined as the points of departure are 

based on the same study and toxicological effects of decreased body weight.

4.5.3 Cancer Classification and Risk Assessment Recommendation

In the 2002 Preliminary Human Health Risk Assessment, Tebuthiuron was classified as a Group 

D compound “not classifiable as to human carcinogenicity.” There is no concern for 

mutagenicity. In the rat carcinogenicity study, there was no evidence of carcinogenicity. The 

mouse carcinogenicity study was inadequate to determine carcinogenic activity due to the lack of 

adverse effects at the highest dose tested. In 2004, HED’s Dosage Adequacy Review Team 

(DART) determined that the mouse carcinogenicity needs to be repeated due to the lack of 

effects at the highest dose tested. On March 13, 2014, however, HASPOC, based on a weight of 

evidence approach considering all of the available hazard and exposure information for 

tebuthiuron concluded that a repeat mouse study is not required. Despite the inadequacy of the 

mouse carcinogenicity study, EPA has determined that an additional mouse carcinogenicity 

study is not needed and that the rat chronic/carcinogenicity study will be adequate for assessing 

chronic risk, including cancer. This finding is based upon the following conclusions: (1) the rat 

is more sensitive than the mouse for the chronic assessment; (2) the effect seen in the most 

sensitive species (rats) and most sensitive sub population (i.e., F1 offspring) in the twogeneration rat reproduction study has been used as the point of departure for the chronic 

assessment; (3) a new mouse study would only use doses well above the current POD for the 

chronic assessment; and (4) even if a new mouse study identified positive carcinogenicity 

effects, that finding would not result in the adoption of a quantitative linear assessment of cancer 

risk due to the negative carcinogenicity finding in the rat study and the lack of a positive finding 

for genotoxicity.
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 18 of 57

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

Assessment

Table 4.5.4. Summary of Toxicological Doses and Endpoints for Tebuthiuron for Use in Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD/PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary

(General Population) No appropriate endpoint attributable to a single dose was identified. An acute RfD was not established.

Acute Dietary

(Females 13 to 49 

years of age)

NOAEL = 10 

mg/kg/day

UFA 10x

UFH 10x

FQPA SF = 1X

aRfD = 0.1 

mg/kg/day

aPAD = 0.1 

mg/kg/day

Developmental Toxicity (rabbit)

MRIDs: 00020644, 40776301

LOAEL = 25 mg/kg/day, based on 

significantly decreased fetal weights and 

increased resorptions. 

Chronic Dietary

(All populations)

Parental 

NOAEL=14 

mg/kg/day

UFA 10x

UFH 10x

FQPA SF = 1X

cRfD =cPAD 0.14 

mg/kg/day

2-Generation Reproductive Toxicity

MRIDs: 00090108

Parental LOAEL = 26 mg/kg/day, based on 

decreased body weights in F1 females (13%)

Incidental Oral

Short-Term

(1-30 days)

Offspring 

NOAEL = 14 

mg/kg/day

UFA 10x

UFH 10x

FQPA SF = 1X

LOC = 100x

2-Generation Reproductive Toxicity

MRIDs: 00090108

Offspring LOAEL = 26 mg/kg/day, based on 

decreased pup body weights on PND 21 in the 

F1 and F2 generation (5-8%).

Dermal

Short-Term

(1 – 30 days) and 

Intermediate-Term

(1 – 6 months)

NOAEL = 14

mg/kg/day

UFA 10x

UFH 10x LOC = 100x

2-Generation Reproductive Toxicity

MRIDs: 00090108

Parental LOAEL = 26 mg/kg/day, based on 

decreased body weights in F1 females (13%)

Offspring LOAEL = 26 mg/kg/day, based on 

decreased pup body weights on PND 21 in the 

F1 and F2 generation (5-8%).

Inhalation

Short-Term

(1-30 days) and 

Intermediate-Term

(1 – 6 months)

NOAEL = 14

mg/kg/day

UFA 10x

UFH 10x

FQPA UFDB = 

10X

LOC = 1000x

2-Generation Reproductive Toxicity

MRIDs: 00090108

Parental LOAEL = 26 mg/kg/day, based on 

decreased body weights in F1 females (13%)

Offspring LOAEL = 26 mg/kg/day, based on 

decreased pup body weights on PND 21 in the 

F1 and F2 generation (5-8%).

Cancer (oral) Classification: "Not classifiable as to human carcinogenicity".

Point of Departure (POD) = A data point or an estimated point 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 animals to humans (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFDB= Data base Uncertainty Factor. FQPA SF = FQPA Safety Factor. aPAD = 

acute population adjusted dose. cPAD = chronic population adjusted dose. RfD = reference dose. 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 19 of 57

4.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for tebuthiuron, EPA reviewed 

these data and selected the most sensitive endpoints for relevant risk assessment scenarios from 

the existing hazard database. However, as required by FFDCA section 408(p), tebuthiuron is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

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

website.2

5.0 Dietary Exposure and Risk Assessment 

5.1 Summary of Plant and Animal Metabolism Studies

Plant

 

1

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.

2

2 http://www.epa.gov/endo/
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 20 of 57

Tebuthiuron metabolism in grass is adequately understood. All data requirements for the 

magnitude of the residue in plants have been evaluated and deemed acceptable. A metabolism 

study (MRID 00020756) was submitted in which a [14C] tebuthiuron solution (labeled in the 

5-position of the thiadiazole ring; specific activity of 16.9 μCi/mg) was applied to the surface of 

the soil in which 10-week old tall fescue (0.374 lb ai/A), little bluestem and Indian grass (0.75 lb 

ai/A.) were grown. The residues of concern are the parent compound and its metabolites 103 

(OH), 104, and 109 (Dodd, N., 12/10/87). See Appendix B for structures. Two major metabolic 

pathways are involved: N-demethylation of tebuthiuron to form 104 and alkyl hydroxylation of 

the dimethylethyl side chain to form 103(OH). 

Livestock

The regulatory requirements for data depicting the magnitude of the residue in milk, and 

livestock tissues are fulfilled. The livestock feeding study (MRID 43703201) depicting the 

magnitude of the residue in milk, and livestock tissues (fat, meat, liver, and kidney), demonstrate 

a transfer of tebuthiuron residues. The residues of concern in milk are tebuthiuron and 

metabolites 104, 104(OH), 106, 109; the residues of concern in livestock commodities are 

tebuthiuron and its metabolites 104, 106, 108, and 109. No poultry or swine feed items are 

associated with the registered uses on grass; there is no reasonable expectation of detectable 

residues of tebuthiuron and its metabolites in poultry and swine commodities resulting from the 

uses and no tolerances are needed. 

Current tolerances are adequate to cover secondary transfer of residues.

Rotational Crops

Tebuthiuron is only used for the restoration of grasses in natural rangelands, permanent 

pasturelands and in non-cropland areas such as energy and transportation rights-of-ways; 

rotational crops are not concomitant to these uses.

5.1.1 Summary of Environmental Degradation

Tebuthiuron is persistent, mobile and can potentially leach to ground water. Tebuthiuron is not 

lipophilic. It is resistant to biological and chemical degradation, and its principle route of 

dissipation in the environment appears to be off-site transport. Transport to ground water 

through leaching and to surface water through run-off and off-target spray drift are likely as a 

result of the chemical’s environmental persistence and low adsorption to soil. Based on the 

available data, the parent and degradate 104 (residues of concern) are persistent and mobile. 

5.1.2 Residues of Concern Summary and Rationale

For dietary risk assessment, HED previously concluded that the residue of concern in plants are 

the parent compound and its metabolites 103, 103(OH), 104, and 109. As stated previously, the 

residues of concern in livestock commodities (fat, meat, kidney, and liver) are tebuthiuron and its 

metabolites 104, 106, 108, and 109; the terminal residues of concern in milk are tebuthiuron and 

metabolites 104, 104(OH), 106, 109, and 109(OH). 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 21 of 57

For the drinking water assessment, HED previously concluded that the parent compound and 

degradate 104 should be included in the drinking water risk assessment. Additionally, the 

metabolism assessment review committee (MARC) committee did not recommend including the 

other degradates in a drinking water risk assessment because they were not likely to be present. 

Metabolites 103(OH), 104(OH) and 109 (OH) were not detected in the environmental fate 

studies although identified as residues of concern. The drinking water risk assessment included 

metabolites 106, 108 and 109 based on aerobic soil metabolism and soil photolysis assumptions 

and on similarity in structure and that they have comparable chemical properties as the parent 

compound. The structures are shown in Appendix B, Figure B.1.

5.2 Food Residue Profile

Tebuthiuron is not registered for agricultural uses. Its use is limited to application to grasses. 

No residues in raw agricultural commodities are expected. However, residues are seen in 

livestock feedstuff, and those residues do appear to transfer to livestock fed tebuthiuron-treated 

feedstuffs. The highest residues are found in meat by products (kidney/liver), with residues also 

found in fat, meat, and milk.

5.3 Water Residue Profile

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

Environmental Fate and Effects Division (EFED) in the following memorandum: “Tier II 

Estimated Surface Drinking Water Concentrations and Estimated Ground Water Concentration 

(EDWCs) for Tebuthiuron for Use in Human Health Risk Assessment,” (D414241, I. AbdelSaheb,01/16/2014). Water residues were incorporated in the dietary exposure evaluation 

modeling (DEEM-FCID) into the food categories “water, direct, all sources” and “water, 

indirect, all sources.” 

Only the parent compound and degradates 104, 106, 108, and 109 were included in the drinking 

water exposure estimates (i.e., Appendix B, Table B3 and Figure A) for the details. The values 

entered into the dietary exposure assessment model to assess the contribution from drinking 

water were specified by the results of the Pesticide Root Zone Model for Groundwater, (PRZMGW) modeling program. No percent crop area (PCA) adjustment is applied to estimated ground 

drinking water concentrations (EDWCs). 

EFED has developed six standard drinking water modelling scenarios that represent vulnerable 

watersheds in specific areas in the country. “Crop-specific” modelling scenarios are not 

available for all crops, however each groundwater scenario represents a different region known 

to be vulnerable to groundwater contamination. For chemicals which have a very limited 

number of labeled crops, as long as those limited crops are grown all over the country, the 

maximum registered application rate is used in each of the six modelling scenarios. For 

tebuthiuron, which is registered on grasses only, the water number derived from using the grass 

rate in the Wisconsin corn scenario. The scenario that results in the highest estimated 

environmental concentration, is used in the dietary assessment as an estimate of the drinking 

water concentrations that would arise in that vulnerable watershed from the specific registered 
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 22 of 57

uses. This scenario does not imply that the pesticide is actually registered for use on corn. Since 

the WI corn scenario produced the highest EDWCs and it was used in the dietary assessment. 

See Appendix B, Table B4 for summary of EDWCs residues. 

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

The unrefined chronic dietary exposure and risk analysis is based on tolerance-level residues, 

direct incorporation of drinking water residues (chronic) and the DEEM default processing factor

for dried beef. The partially refined acute dietary exposure and risk analysis is based on 

tolerance-level residues, time series distribution of drinking water residues and the DEEM 

default processing factor for dried beef.

5.4.2 Percent Crop Treated Used in Dietary Assessment

Percent crop treated refinements were not applicable to these assessments, tolerance-level 

residues are established on animal and non-food grass (forage and hay) commodities.

5.4.3 Acute Dietary Risk Assessment

The acute dietary food (tolerance level residues) and water (time series water distribution) risk 

estimates reported in the tables are for females 13-49 years old. An acute assessment was 

performed only for females 13-49 years old since an acute endpoint for the general population 

was not selected. The resulting dietary (food and water) risk estimates are not of concern (less 

than 100%); acute dietary risk for females 13 – 49 years old is 93% of the aPAD at the 95th

percentile.

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary risk estimates reported in the tables below are for the general U.S. 

Population, all infants (<1 year old), children 1-2, children 3-5, children 6-12, youth 13-19, 

females 13-49, adults 20-49, and adults 50-99 years. The resulting dietary risk estimates are not 

of concern; (less than 100%); the most highly exposed population subgroup is all infants at 72% 

of the cPAD, while the general U.S. population utilized 30% of the cPAD. 

5.4.5 Summary Table

Table 5.4.5 Summary of Dietary (Food and Drinking Water) Exposure and Risk for Tebuthiuron

*The subpopulation(s) with the highest risk estimates bolded

Population Subgroup

Acute Dietary (95 th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day)

% 

aPAD

Dietary Exposure

(mg/kg/day)

% 

cPAD

General U.S. Population 0.042379 30

All Infants (<1 year old) 0.100488 72

Children 1-2 years old 0.088184 63
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 23 of 57

Table 5.4.5 Summary of Dietary (Food and Drinking Water) Exposure and Risk for Tebuthiuron

*The subpopulation(s) with the highest risk estimates bolded

Population Subgroup

Acute Dietary (95 th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day)

% 

aPAD

Dietary Exposure

(mg/kg/day)

% 

cPAD

Children 3-5 years old 0.064471 46

Children 6-12 years old 0.043157 31

Youth 13-19 years old 0.031694 23

Adults 20-49 years old 0.039849 29

Adults 50-99 years old 0.039135 28

Females 13-49 years old 0.093157 93 0.039754 28

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no registered residential uses for tebuthiuron. Residential handler and post-application 

exposure assessments are not included in this document.

6.1 Residential Bystander Post-application Inhalation Exposure

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

assessment was not performed for tebuthiuron at this time. 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, 20103. The Agency is 

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

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

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

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

exposure assessment for tebuthiuron.

6.2 Spray Drift

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

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

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

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

estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

 

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 24 of 57

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

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

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

prevent them.4 Direct exposures would include inhalation of the spray plume or being sprayed 

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

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

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

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

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

considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a 

residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of tebuthiuron. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDRIFT (v2.1.1) model and the 

Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of 

Spray Drift Policy. Once the deposited residue values were determined, the remainder of the 

spray drift assessment was based on the algorithms and input values specified in the recently 

revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs). 

A screening approach was developed based on the use of the AgDRIFT model in situations 

where specific label guidance that defines application parameters is not available.5,6 AgDRIFT is 

appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and 

groundboom sprayers. When AgDRIFT was developed, a series of screening values (i.e., the 

Tier 1 option) were incorporated into the model and represent each equipment type and use 

under varied conditions. The screening options specifically recommended in this methodology 

were selected because they are plausible and represent a reasonable upper bound level of drift for 

common application methods in agriculture. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. In all cases, each scenario is to 

be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are 

not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are 

not allowed). Section 6.2.1 and Appendix D provide the screening level drift related risk 

estimates. 

In many cases, risks are of concern when the screening level estimates for spray drift are used as 

the basis for the analysis. In order to account for this issue and to provide additional risk 

management options additional spray drift deposition fractions were also considered. These drift 

estimates represent plausible options for pesticide labels 

 

4 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

5http://www.agdrift.com/ 

6 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors should 

be aware and characterize these appropriately.
Tebuthiuron Human Health Risk Assessment DP No. D414218

Page 25 of 57

6.2.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a 

result of the screening level agricultural application scenarios. Tebuthiuron can be applied via 

groundboom, and aerial equipment at a maximum rate of 6 lb ai/acre to large acreages of 

pastureland/rangeland as well as for total vegetative control in non-cropland areas. The 

recommended drift scenario screening level options are listed below:

 Groundboom applications; are based on the AgDRIFT option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

 Aerial applications: are based on the use of AgDRIFT Tier 1 aerial option for a fine to 

medium spray type and a series of other parameters which will be described in more 

detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire 

application/drift event).7

In addition to the screening level spray drift scenarios described above, additional results are 

provided which represent viable drift reduction technologies (DRTs) that represent potential risk 

management options. In particular, different spray qualities have been considered as well as the 

impact of other application conditions (e.g., boom height, use of a helicopter instead of fixed 

wing aircraft, crop canopy conditions).

Dermal risk estimates based on 100% absorption were calculated for adults. Dermal and 

incidental oral risk estimates for children 1 to <2 years old were combined because the toxicity 

endpoint for each route of exposure is the same. The total applicable level of concern is 100 so 

MOEs < 100 represent risk estimates of concern. Adult dermal and children’s (1 to <2 year old) 

dermal and incidental oral risk estimates from indirect exposure to tebuthiuron related to spray 

drift result in buffers that range from 0 feet to greater than 150 feet depending on the nozzle type, 

droplet size, and application equipment. Aerial application has more risk estimates of concern. 

Dermal absorption data could lead to refinement in the spray drift analysis. 

Spray drift analysis results are presented in Appendix D Tables D.1 and D.2. Appropriate drift 

reduction technologies such as changing the spray type/nozzle configuration to coarser spray 

applications may in less drift and reduced risk concerns (i.e., higher MOEs) from aerial 

applications. Similarly, using coarser sprays and lowering boom height for groundboom 

sprayers reduces risk concerns.

 

7 AgDRIFT allows for consideration of even finer spray patterns characterized as very fine to fine. However, this spray pattern 

was not selected as the common screening basis since it is used less commonly for most agriculture. .
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 26 of 57

7.0 Aggregate Exposure/Risk Characterization

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

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

In an aggregate assessment, exposures from relevant sources are added together and compared to 

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

aggregated. When aggregating exposures and risks from various sources, HED considers both 

the route and duration of exposure. There are no residential uses of tebuthiuron; therefore, the 

aggregate risk includes only exposure from food and drinking water. The acute and chronic 

dietary risk estimates are not of concern (less than 100%) of the aPAD and cPAD, respectively 

(see Section 5.0 for specific information on the dietary exposure estimates). 

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 tebuthiuron and any other substances and tebuthiuron does not appear to produce a toxic 

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

EPA has not assumed that tebuthiuron 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

9.1 Short-/Intermediate Handler Risk

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

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

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

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

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

manner specific to each application event. 

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

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

proposed uses of tebuthiuron. The quantitative exposure/risk assessment developed for 

occupational handlers is based on the following scenarios: 

 Mixing/loading DF/WDG for aerial application;

 Mixing/loading DF/WDG for groundboom application;
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 27 of 57

 Loading P/G for aerial application;

 Loading P/G for tractor drawn spreader application;

 Applying DF/WDG by aerial application;

 Applying DF/WDG by groundboom application;

 Applying P/G for aerial application; 

 Applying P/G for tractor drawn spreader application;

 Loading/applying P/G for application with belly grinder;

 Loading/applying P/G for application with a rotary push-type spreader;

 Mixing/loading/applying DF/WDG for mechanically pressurized handgun 

application;

 Mixing/loading/applying DF/WDG for manually pressurized handwand application; 

 Mixing/loading/applying DF/WDG for backpack application; 

 Applying P/G by cup;

 Applying P/G by spoon;

 Applying P/G by shaker can; 

 Applying P/G by hand; and

 Flaggers from aerial application of spray and granules.

Chemigation applications are prohibited on the product labels.

Exposure is most likely to be short (1 to 30 days) and intermediate-term (1 to 6 months) given 

the use pattern and limitations. There are no agricultural crop use sites and the recommended 

timing of application is prior to the resumption of active seasonal growth in the spring when the 

ground is not frozen or before expected seasonal rainfall. Applications are limited to once every 

two to three years and to twice every six years. However it is possible that a commercial 

applicator could apply the product over a period of weeks within a region. Therefore, based on 

the use pattern short-term and intermediate-term exposures are expected for tebuthiuron. 

Estimates of dermal and inhalation exposure were calculated for various levels of personal 

protective equipment. Results are presented for “baseline,” defined as a single layer of clothing 

consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no 

respirator, as well as baseline with the addition of various levels of PPE as necessary (e.g., 

gloves, respirator, engineering control, etc). Worker protection standard (WPS) language should 

appear on all registered labels. Currently two out of the three pelleted tebuthiuron formulations 

do not have any WPS listed on the labels. The DF and WDG formulations list PPE as baseline 

dermal attire plus gloves. The granular formulations direct tractor drawn spreaders and loaders 

to use a respirator with NIOSH approved filter with the addition of baseline dermal plus 

chemical resistant gloves

Based on the assessment of registered uses, there are risk estimates of concern (i.e., dermal 

MOEs <100 and inhalation MOEs < 1000) for the short/intermediate dermal and inhalation 

exposure. In evaluating handler exposure scenarios, the dermal MOE values range from 0.18 to 

7,100 at baseline dermal (i.e., no gloves), 1.8 to 71,000 with gloves, and 2.4 to 71,000 with 

double layer protection consisting of baseline dermal with the addition of a coverall. In 

evaluating handler exposure scenarios, the inhalation MOE values range from 26 to 64,000 at 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 28 of 57

baseline inhalation (i.e., no respirator), 130 to 320,000 with PF5 respirator, 260 to 640,000 with a 

PF10 respirator, and 970 to 480,000 with engineering controls. See Appendix E, tables E.1.1 

through E.1.3 for occupational risk estimate summary.

A total aggregated risk index (ARI) was used since the LOC values for dermal exposure (100) 

and inhalation exposure (1000) are different. The target ARI is 1; therefore, ARIs of less than 1 

are risk estimates of concern. Several of the occupational handler scenarios remain a risk of 

concern even with the addition of doubler layer dermal PPE consisting of double layer dermal 

wear, respirators, and engineering controls. These scenarios are as follows:

 Mixing/loading of DF/WDG and P/G for aerial applications on pastureland/rangeland (4

and 6 lb ai/acre) has a baseline PPE combined 0.1 ARI value. ARI values ranges from 

0.02-0.25 with various PPE additions including engineering control such as a closed 

mixing/loading system;

 Mixing/loading P/G for aerial applications on non-crop land (6 lb ai/acre) has a baseline 

PPE combined 0.06 ARI value. ARI values ranges from 0.07-0.16 with various PPE 

additions including engineering control such as a closed mixing/loading system;

 Aerial application of P/G on pastureland, which resulted in a combined 0.16 ARI value 

with the use of engineering controls and on non-crop land a combined ARI value of 0.11.

 Flagger exposure to aerial spray of tebuthiuron on pastureland resulted in an ARI of 0.74

with double layer dermal PPE and PF10 respirator;

 Mixing/Loading/Applying DF/WDG with backpack, manually pressurized handgun, 

mechanically pressurized handwand resulted in an ARIs <1 even with double layer 

dermal PPE and PF10 respirator;

 Mixing/Loading/Applying P/G with a belly grinder, and hand dispersal, resulted in ARIs 

<1 even with double layer dermal PPE and PF10 respirator. 

9.2 Short-/Intermediate-term Post-Application Risk

9.2.1 Dermal Post-application Risk

Occupational post-application dermal exposure from workers re-entering tebuthiuron treated 

areas is not anticipated because the chemical is a non-selective herbicide used in non-agricultural 

areas such as pastureland/rangeland, industrial, and rights-of-way sites. Occupational postapplication exposures are not thought to occur because reentry is unlikely. Labels currently 

instruct workers to not enter fields until dusts have settled and delay grazing until one year after 

application. However, some of the labels use the term haying. If pastureland is intended for 

haying harvest the REI specified on labels should be based on the acute toxicity of tebuthiuron. 

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

to protect agricultural workers from post-application exposures to tebuthiuron from harvesting 

hay.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 29 of 57

9.2.2 Inhalation Post-application Risk

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

assessment was not performed for tebuthiuron at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III) and low vapor pressure (2 x 10-6 mm hg at 25 degrees 

Celsius). However there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

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

Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 20108. The 

Agency is in the process of evaluating the SAP report as well as available post-application 

inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and 

procedures, to identify the need for and, subsequently, the way to incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for tebuthiuron.

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

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

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

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

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

inhalation exposure scenarios.

 

8 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 30 of 57

10.0 References

Barnes, P. Y., July 23, 2009, D363983, Tebuthiuron. Revised: Registration Review Scoping

Document for Human Health Assessments.

Barnes, Y., January 28, 2010, 28, D372760, Tebuthiuron: Response to comments from Dow Agro 

Sciences on the Registration Review Summary Document (Docket EPA-HQ-OPP-2009-0327).

Barnes, P. Y., May 23, 2014, D418910, Tebuthiuron. Dietary Memo for Preliminary Human

Risk Assessment for Registration Review.

BEAD Memo August 29, 2013 Tebuthiuron Screening Level Usage Analysis (SLUA) Reporting 

years: 2004-2011.

Bobowiec, B., April 15, 2014, D418911, Tebuthiuron. Occupational and Residential

Assessment to Support Registration Review for Use on Pastureland, Rangeland, Non-Crop

Industrial Areas, and Rights-of-Ways.

Burnam, W., January 31, 2005, D312380, TXR 0054232: Tebuthiuron Waiver Requests.

Corbin, M. February 2, 2002, D279066 Addendum to TRED Drinking Water Assessment for 

Tebuthiuron.

Deschamp, P. April 22, 2002, D274580, Tebuthiuron: Preliminary Human Health Risk 

Assessment. HED Chapter for the Tolerance Reassessment Eligibility Decision (TRED). 

Funk, S., D217379, December 05, 1995, Tebuthiuron: Ruminant Feeding Study (171-4(j)).

CBRS No. 15883. MRID 43703201.

Funk, S Tebuthiuron, November 22, 1995, D223089, Storage Stability in Support of the

Ruminant Feeding Study (171-4(e; j)). CBRS No. 16937. MRID 43439301.

Hawkins, M., May 7, 2009, Update Review of Tebuthiuron Incident Reports.

Ibrahim, A., October 31, 2013, D414241, Tier II Estimated Surface Drinking Water

Concentrations and Estimated Ground Water Concentrations (EDWCs) for Tebuthiuron for Use

in Human Health Risk Assessment.

Ibrahim, A., January 16, 2014, D414241, Tier II Estimated Surface Drinking Water

Concentrations and Estimated Ground Water Concentrations (EDWCs) for Tebuthiuron for Use

in Human Health Risk Assessment.

Leshin, J., Executive Secretary, May 27, 2014, TXR 0056925, Tebuthiuron: Report of 

HASPOC.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 31 of 57

Kidwell, J., Executive Secretary, December 9, 2004, TXR 0052580, Tebuthiuron: Report of 

the Dose Adequacy Review Team (DART).

Piper, S., April 03, 2002. D281821, Acute and Chronic Dietary Exposure Assessments for the 

TRED.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 32 of 57

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 Tebuthiuron are in Table 1. Use 

of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A1: Summary of Tebuthiuron toxicology data requirements. 

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-Day Dermal..............................................................

870.3250 90-Day Dermal..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

yes

yes

yes

yes

no

no

870.3700a Developmental Toxicity (rodent) ..................................

870.3700b Developmental Toxicity (nonrodent) ............................

870.3800 Reproduction.................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

yes

no

yes

yes

waived1

yes

waived1

waived1

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian ...............

870.5395 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)......................................

870.6100b 90-Day Neurotoxicity (hen) ..........................................

870.6200a Acute Neurotox. Screening Battery (rat)........................

870.6200b 90-Day Neuro. Screening Battery (rat) ..........................

870.6300 Developmental Neurotoxicity .......................................

no

no

yes

yes

CR

no

no

waived1

waived1

no

870.7485 General Metabolism......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

no

yes

Special Studies for Ocular Effects no no

1) Acute and subchronic neurotoxicity studies, chronic/carcinogenicity study in the rat, and a carcinogenicity study in the mouse are not required 

for Tebuthiuron (HASPOC TXR0056927
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 33 of 57

A.2 Toxicity Profiles

Table A2: Tebuthiuron Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification 

/Doses Results

870.3100 90-Day oral toxicity 

(Haerlan Rat) 

00020662 (1972)

Acceptable/Guideline

0, 20, 50, and 125 mg/kg/day

NOAEL = 50 mg/kg/day

LOAEL = 125 mg/kg/day based on decreased body 

weight (25-28%) and an increase in slight 

vacuolization of the pancreatic acinar cells. 

870.3100 90-Day oral toxicity 

(Beagle Dog)

00020663 (1972)

Acceptable/Guideline

0, 12.5, 25, and 50 mg/kg/day

NOAEL = 25 mg/kg/day

LOAEL = 50 mg/kg/day based on significant 

decreases in body weight and increased ALP activity. 

870.3200 21/28-Day dermal 

toxicity 

00149733 (1985)

00160796 (1986)

Acceptable/Guideline

0, 1000 mg/kg/day

NOAEL = 1000 mg/kg/day

No treatment related effects were observed.

870.3700a Prenatal 

developmental 

(Harlan Rats)

00020803 (1972)

40485801 (1972)

Acceptable/Guideline

0, 37, 72, and 110 mg/kg/day

GD 6-14

Maternal NOAEL = 110 mg/kg/day

Developmental NOAEL = 110 mg/kg/day

No treatment related effects were observed.

870.3700b Prenatal 

developmental (Dutch 

rabbits) 

00020644 (1975)

40776301 (1988)

Acceptable/Guideline

0, 10, and 25 mg/kg/day

Maternal NOAEL = 10 mg/kg/day

 LOAEL = 25 mg/kg/day based on increased 

resorptions at the high-dose. 

Developmental NOAEL = 10 mg/kg/day

 LOAEL = 25 mg/kg/day based on 

significantly decreased fetal weights.

870.3800 2-Generation 

Reproduction and 

fertility effects

(Wistar rat)

00090108 (1981)

Acceptable/Guideline

0, 14, and 30 mg/kg in males and 

0, 14, and 26 mg/kg in females. 

Parental NOAEL = 14 mg/kg/day

 LOAEL = 26 mg/kg/day based on 

decreased body weights in F1 females (13%). 

Reproductive NOAEL = 26 mg/kg/day.

No effects were observed on reproductive parameters 

as measured by sperm morphology, fertility index for 

females, and the number of litters produced. 

Offspring NOAEL = 14 mg/kg/day

 LOAEL = 26 mg/kg/day based on 

decreased pup body weights on PND 21 in the F1 and 

F2 generation (5-8%). 

870.4100b Chronic toxicity 

(Beagle dog, capsule) 

00146801 (1985)

Acceptable/Guideline

0, 12.5, 25, and 50 mg/kg/day

NOAEL = 25 mg/kg/day

LOAEL = 50 mg/kg/day based on decreased body 

weight (-12.5%), increased ALT (4-5 fold), AP (3-

fold), and significantly increased absolute and relative 

liver weights.

870.4200 Carcinogenicity

(Harlan ICR mice) 

00020717 (1986)

Unacceptable/Guideline

0, 60, 120, and 240 mg/kg/day

NOAEL = 240 mg/kg/day

No significant treatment-related effects were identified. 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 34 of 57

Table A2: Tebuthiuron Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification 

/Doses Results

870.4300 Combined chronic 

toxicity/carcinogenici

ty (Sprague-Dawley 

rat) 

00020714 (1976)

00098190 (1981)

40870101 (1988)

Unacceptable/Guideline

0, 20, 40, and 80 mg/kg/day

No NOAEL may be established for this study as 

several major deficiencies were identified. 25% or 

fewer animals were living at study termination in all 

groups. Additionally, respiratory infections were 

prevalent among the controls and treated groups 

confounding the study results. 

870.5100 Bacterial reverse gene 

mutation assay

MRID 00141691 (1984)

Acceptable/Guideline

There was no increase in mutant colonies in tested 

bacterial strains exposed up to the limit dose (5000 

μg/plate) with or without S9 activation.

870.5100 Bacterial reverse gene 

mutation assay

MRID 00141690 (1984)

Acceptable/Non-Guideline

There was no increase in mutant colonies in any S. 

typhimurium or E. coli tested strain exposed to 

tebuthiuron (98.0 %) with or without metabolic 

activation. There was no evidence of induced mutant 

colonies over background in tested S. typhimurium 

strains and E. coli strains with or without S9 

activation. 

870.5300 In vitro mammalian 

cell gene mutation

MRID 00145041 (1984)

Acceptable/Guideline

In a mammalian cell gene mutation assay in vitro, 

cultures of mouse lymphoma were exposed to 

Tebuthiuron (98.0%) technical at concentrations 

limited by cytotoxicity. Mutations were not induced at 

any concentration with S9- activation. Tebuthiuron was 

considered weakly mutagenic but only in the absence 

of metabolic activation. No evidence of an increased 

mutant frequency was observed in the presence of 

metabolic activation.

870.5550 Unscheduled DNA 

synthesis in 

mammalian cell 

culture

MRID 40750901 (1988)

Acceptable/Guideline

In an unscheduled DNA synthesis (UDS) assay, primary rat hepatocyte cultures were exposed to 

Tebuthiuron (99.1 %) to the limit of cytotoxicity 

(900 μg/mL). UDS activity was evaluated at 

concentrations up to 800 μg/mL and there was no 

evidence of induction of UDS. There was no evidence 

that UDS, as determined by radioactive tracer 

procedures [nuclear silver grain counts] was induced.

870.5375 In vitro mammalian 

cell chromosome 

aberration

MRID 41134101 (1989)

Acceptable/Guideline

In a mammalian chromosome aberration assay, 

Chinese Hamster Ovary (CHO) cell cultures were 

exposed to Tebuthiuron (99.08%) at concentrations 

limited by cytotoxicity. A significant increase in the 

percent of cells with aberrations was noted in 

nonactivated and activated cultures at cytotoxic doses. 

The predominant types of aberrations were 

chromosome and chromatid breaks. No significant 

increases were observed at lower concentrations; 

however, rare complex aberrations, such as triradials, 

quadriradials and complex rearrangements were noted, 

providing further support for clastogenicity. Positive 

control values were acceptable. There was evidence of 

an increase in structural chromosomal aberrations over 

background in the presence and absence of metabolic 

activation at cytotoxic doses.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 35 of 57

Table A2: Tebuthiuron Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification 

/Doses Results

870.5915 In vivo sister 

chromatid exchange

MRID 40750902 (1988)

Acceptable/Guideline

In an in vivo cytogenetic assay measuring sister 

chromatid exchange (SCE) frequency in Chinese 

hamster bone marrow cells female Chinese hamsters 

(3/group) were administered single oral doses of 

tebuthiuron (99.1%, Lot No. 729AS7) in 10% aqueous 

acacia at 3000, 4000, or 5000 mg/kg. 

Tebuthiuron was tested up to cytotoxic concentrations. 

Hypo-activity was noted in all treatment groups and 

bone marrow cytotoxicity (as evidenced by an increase 

in the percent division metaphases) was observed at 

5000 mg/kg. There was no increase in the number of 

cells containing SCEs compared to controls at any 

concentration of tebuthiuron tested. 

Cyclophosphamide (50 mg/kg) and vehicle control 

values were acceptable. There was no evidence of an 

increase in SCEs over background.

A.3 Hazard Identification and Endpoint Selection

A.3.1 Acute Reference Dose (aRfD) (Females 13-49 years old)

Study Selected: Developmental Toxicity in rabbits

MRIDs: 00020644 and 40776301

Dose and Endpoint for Risk Assessment: NOAEL= 10 mg/kg/day increased resorptions at 

LOAEL of 25 mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: This study is considered to be the most 

appropriate for acute dietary dose and endpoint selection. Unlike the increased resorptions, the 

fetal body weight reductions at 25 mg/kg/day, were no considered to be an acute effect. Thus, 

the basis for the acute dietary risk assessment for females of reproductive age is the resorptions. 

Note: No endpoint was selected for the general population. The endpoint from the developmental 

rabbit study for females 13-49 would be protective of any clinical signs seen at much higher 

doses in the acute oral toxicity study in rats.

Acute RfD = 

100( )

10mg/kg/day

UF

= 0.1 mg/kg/day

A.3.2 Chronic Reference Dose (cRfD)

Study Selected: 2-Generation Reproduction Study in Rats

MRIDs: 00090108

Dose and Endpoint for Risk Assessment: Parental NOAEL= 14 mg/kg/day. Parental LOAEL 

= 26 mg/kg/day, based on decreased body weights in F1 females (13%).
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 36 of 57

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: The 2-generation reproduction study in 

rats is appropriate for both the population of concern (adults) and the duration of exposure. 

Chronic RfD = 

100( )

14mg/kg/day

UF

= 0.14 mg/kg/day

A.3.3 Incidental Oral Exposure (Short-term, 1-30 days)

Study Selected: 2-Generation Reproduction Toxicity Study in Rats

MRIDs: 00090108

Dose and Endpoint for Risk Assessment: Offspring NOAEL= 14 mg/kg/day based on 

decreased pup body weights on PND 21 in the F1 and F2 generation (5-8%) at the LOAEL of 26 

mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: The endpoint of concern in this study is

appropriate for the population (infant and children) and the duration of concern.

A.3.4. Dermal Exposure (Short-, Intermediate-Term) (Based on e-review post-ToxSAC 

meeting)

Study Selected: 2-Generation Reproduction Toxicity Study in Rats

MRIDs: 00090108

Dose and Endpoint for Risk Assessment: Offspring NOAEL= 14 mg/kg/day based on 

decreased pup body weights on PND 21 in the F1 and F2 generation (5-8%) at the LOAEL of 26 

mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: A dermal risk assessment is being 

conducted for the following reasons 1) physical properties of the chemical support the potential 

for dermal absorption and 2) resorptions observed in the developmental toxicity study occurred 

in the absence of other maternal effects, and therefore, use of the dermal toxicity study which 

does not test pregnant animals may be under-protective as resorptions are not measured. The 2-

generation reproductive toxicity study with a NOAEL of 14 mg/kg was selected as the NOAELs 

and LOAELs are similar (10/14 mg/kg and 25/26 mg/kg), the 14 mg/kg/day NOAEL represents 

a smaller dose spread between the NOAEL/LOAEL of both studies, and is protective of both the 

developmental effects observed in the rabbit and offspring effects in pups. There is no proposed 

long-term use; therefore, risk assessment for long-term dermal exposure is not required.

A.3.5 Inhalation Exposure (Short-, and Intermediate-Term) (Based on e-review post 

ToxSAC meeting)
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 37 of 57

Study Selected: 2-Generation Reproduction Toxicity Study in Rats

MRIDs: 00090108

Dose and Endpoint for Risk Assessment: Offspring NOAEL= 14 mg/kg/day based on 

decreased pup body weights on PND 21 in the F1 and F2 generation (5-8%) at the LOAEL of 26 

mg/kg/day.

Uncertainty Factor: 1000x (10x interspecies extrapolation, 10x intraspecies variability, 10x 

database uncertainty (inhalation study required by HASPOC), 1x FQPA Safety Factor).

Comments on Study/Endpoint/Uncertainty Factors: No route-specific inhalation study is 

available for tebuthiuron. The 2-generation reproductive toxicity study with a NOAEL of 14 

mg/kg was selected as it is protective of both developmental effects in rabbits and offspring 

effects observed in the rats. There is no proposed long-term use; therefore, risk assessment for 

long-term inhalation exposure is not required.

A.4 Executive Summaries

A.4.1 Subchronic Toxicity

870.3100 90-Day Oral Toxicity- Rat

The NOEL is 1000 ppm (50 mg/kg) in the diet based on increased relative liver, kidney, prostate, 

spleen and gonad weights in high-dose males and females. There was also slight vacuolization of 

the pancreatic acinar cells in the high-dose group of both sexes. 

Classification: CORE- Minimum data.

870.3150 90-Day Oral Toxicity – Dog

Anorexia was noted especially in the high-dose animals, leading to weight loss. No mortality was 

observed. Behavior and appearance were unremarkable. No abnormalities were observed in 

hematological or urinalysis studies. 

Clinical chemistry findings indicated increased BUN in the 2000 ppm females; in addition, this 

group exhibited increasing levels of ALP, up to 4-fold over the control group. Females at 1000 

ppm demonstrated increased relative thyroid and spleen weights. 

The LOAEL is 50 mg/kg/day based on significant decreases in body weight and increased 

ALP activity. The NOAEL is 25 mg/kg/day. 

870.3200 21/28-Day Dermal Toxicity – Rat

No effects were observed up to the limit dose. 

A.4.2 Prenatal Developmental Toxicity
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 38 of 57

870.3700a Prenatal Developmental Toxicity Study – Rat

In a developmental toxicity study (MRID 00020803, 40485801), 25 presumed pregnant Harlan 

rats per group were administered tebuthiuron (purity not given; Lot No. 1093-316A-259) at 

dietary concentrations of 0, 600, 1200, or 1800 ppm on gestation days (GD) 6-15, inclusive. 

Doses to the animals were 0, 37, 72, or 110 mg/kg/day, respectively. Individual data for 

maternal body weights and food consumption, cesarean parameters, and fetal examinations were 

given in MRID 40485801. On GD 20, dams were sacrificed and subjected to gross necropsy; 

pancreatic tissue was saved from 10 females/group for histopathological examination. Fetal sex, 

weight, and viability were determined and each fetus was examined for external abnormalities. 

Approximately one-third of all fetuses were fixed in Bouin’s solution for subsequent visceral 

examination and the remainders were cleared for skeletal examination.

All dams survived to terminal sacrifice. No treatment-related clinical signs of toxicity, changes 

in body weight, body weight gain, or food consumption were observed in any group. No 

treatment-related lesions were observed in any dam at necropsy. Pancreatic tissue, as evaluated 

by both gross and microscopic examination, appeared normal.

The maternal NOAEL is 110 mg/kg bw/day.

No differences were observed between the treated and control groups for pregnancy rate, number 

of corpora lutea/dam, number of implantation sites/dam, pre- or post-implantation losses, number 

of fetuses/litter, fetal body weights, or fetal sex ratios. No dead fetuses were observed. No 

treatment-related abnormalities were found in any fetus. 

The developmental NOAEL is 110 mg/kg bw/day.

This study is classified as Acceptable/Guideline and satisfies the requirements for a 

developmental toxicity study [870.3700 (§83-3a)] in rats. It should be noted that test article 

concentrations in the diets were not measured; therefore, it may be possible that the doses to the 

animals were different from nominal.

870.3700b Prenatal Developmental Toxicity Study – Rabbit

In a developmental toxicity study (MRID 00020644, 40776301, 41122401), 15 presumed 

pregnant Dutch belted rabbits per group were administered tebuthiuron (96.5% a.i.; Lot No.: 

B30-23-149) by gavage at doses of 0, 10, or 25 mg/kg/day on gestation days (GD) 6-18, 

inclusive. 

No clinical signs of toxicity were observed in any animal. No effects on body weights, body 

weight changes, or food consumption were noted for the treated groups as compared with the 

controls. No treatment-related lesions were found at gross necropsy. An increase in total early 

resorptions and the percentage of litters with early resorptions was observed in the high-dose 

group. 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 39 of 57

The maternal toxicity LOAEL is 25 mg/kg/day based on increased resorptions at the highdose. The NOAEL is 10 mg/kg/day.

No differences between the treated and control groups were noted for pregnancy rate or numbers 

of corpora lutea, implantations, or fetuses/litter. A decrease in the mean fetal body weight was 

observed at 25 mg/kg/day (17.3%). An increase in total early resorptions and the percentage of 

litters with early resorptions was observed in the high-dose group. Additionally, an increase in 

early resorptions was indicated in the range-finding study at doses of 25 mg/kg/day and above. 

The developmental toxicity LOAEL is 25 mg/kg/day based on decreased fetal body weights 

and increased early resorptions. The developmental toxicity NOAEL is 10 mg/kg/day. 

The developmental toxicity study in the rabbit is classified Acceptable/Guideline and satisfies 

the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in 

the rabbit. 

A.4.3 Reproductive Toxicity

870.3800 Reproduction and Fertility Effects – Rat

In a two-generation reproduction study (MRID 90108), tebuthiuron (Lot No. 00880-1L-1, X35920, 98.0% a.i.) was fed to groups of 25 male and 25 female Wistar rats per dose at dietary 

concentrations of 0, 100, 200, and 400 ppm. The dietary levels corresponded to doses of 6-7, 13-

14, and 26-28 mg/kg/day, respectively, for F0 and F1 males and 7-8, 14-15, and 30-31 

mg/kg/day, respectively, for F0 and F1 females averaged over the premating period only. Adult 

rats of both generation were fed the treated or control diets during the premating period (98 days 

for F0 and 124 days for F1 rats) and during mating, gestation, and lactation of two litters per 

generation. Pups from the F1a litters were selected to parent the F2 generation.

No treatment-related deaths, clinical signs of toxicity, gross lesions, or microscopic lesions were 

observed in adult rats of either generation. No treatment-related effects were observed on body 

weight, body weight gain, food consumption, or food efficiency in F0 male rats, F1 male rats, or 

F0 female rats fed any dose at any time during the study including the premating, mating, 

gestation, and lactation periods. F1 females in the 200 and 400 ppm groups had mean weekly 

body weights 7-9% (not biologically significant) and 8-13% (p<0.01 or <0.05), respectively, less 

than the control group throughout the premating period starting with day 21 for the 200 ppm 

group and day 7 for the 400 ppm group. Weight gain over the entire premating period was 7% 

(N.S.) less than controls for 200 ppm group F1 females and 14% (p<0.05) less for the 400 ppm 

group. Cumulative food consumption was not significantly affected, but food efficiency was 

reduced by 13% (p<0.01) for 400 ppm group F1 females. It is important to note that the body 

weight decreases of F1 parents occurred only at the high-dose where F1 pups had impaired body 

weight gain. Throughout the database, adult rat body weight impairment does not begin until 

doses 3 to 4 fold higher than administered in this study. 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 40 of 57

The parental systemic LOAEL was established at 400 ppm (26 mg/kg/day) based on 

decreases in body weight and weight gain in F1 female rats. The parental systemic NOAEL 

was established at 200 ppm (14 mg/kg/day). 

No effects were observed on reproductive parameters as measured by sperm morphology, 

fertility index for females, and the number of litters produced.

The reproductive LOAEL was not established; the NOAEL was established at 400 ppm (26 

mg/kg/day).

Biologically significant decreases in pup body weights (5-8%) were observed on PND 7-21 in 

the F1 and F2 litters. 

The offspring LOAEL was established at 400 ppm (26 mg/kg/day) based on decrease pup 

body weights on PND 7-21. The offspring NOAEL was established at 200 ppm (14 

mg/kg/day).

This study is classified Acceptable/Guideline and satisfies the guideline requirement for a twogeneration reproductive study (OPPTS 870.3800, §83-4) in the rat. This study was conducted 

years before the test guidelines were established; therefore, some of the elements of a twogeneration reproduction study were not included in this study. Nevertheless, this study had a 

sufficient number of required elements to be used for the evaluation of reproductive and 

offspring toxicity. The reviewer notes that the rats could have tolerated a higher dose, which may 

have allowed for better characterization of tebuthiuron toxicity to developing rats. 

A.4.4 Chronic Toxicity

870.4100b Chronic Toxicity – Dog

All animals survived to scheduled termination. Clinical signs of toxicity in high-dose animals 

included anorexia, emesis, and diarrhea. Absolute body weights for females and food 

consumption for males and females were not affected by treatment. Body weights of the highdose males were less than those of the controls throughout most of the study with statistical 

significance attained occasionally. Overall weight gains by the high-dose males and females 

were 67% and 82%, respectively, of the control levels. No treatment-related ophthalmological 

lesions, changes in urinalysis parameters, or microscopic lesions were noted and gross necropsy 

was unremarkable.

Thrombocyte counts were significantly (p  0.05) increased in high-dose males at 6 and 12 

months as compared with the controls. Alanine aminotransferase (ALT) levels were increased in 

males after 1 month and in females after 3 months to 186-529% and 228-407%, respectively, of 

the control group levels. In addition, alkaline phosphatase (AP) levels in males were increased 

to 283-408% of the control levels at 6 and 12 months. Statistical significance was not attained at 

all-time points for the increases in enzyme levels due to large variability between individual 

animals.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 41 of 57

Absolute liver weights were significantly (p  0.05) increased in the high-dose males and 

females. No other differences in absolute organ weights were found. Also for the high-dose 

groups, significant (p  0.05) differences in organ weights relative to final body weight included 

increased relative liver weights in males and females, increased relative kidney weights in 

females, and increased relative thyroid weights in males.

The LOAEL was established at 50 mg/kg/day based on clinical signs (anorexia, emesis, and 

diarrhea), decreased body weight gains, increased alanine aminotransferase and alkaline 

phosphatase (males only) levels, increased absolute and relative liver weights, increased 

relative kidney weights (females only), and increased relative thyroid weights (males only). 

The NOAEL was established at 25 mg/kg/day.

This study is classified as Acceptable/Guideline and satisfies the guideline requirements for a 

chronic toxicity study [OPPTS 870.4100 (83-1b)] in dogs.

A.4.5 Carcinogenicity

870.4300a Combined Chronic Toxicity/Carcinogenicity – Rat

In a chronic toxicity/carcinogenicity study (MRID 0020714), tebuthiuron (>97% a.i., lot number, 

6SG43 and B30-23-149) was administered to male and female Wistar rats (40/group/sex) at 

dietary concentrations of 400, 800, or 1600 ppm (20, 40, and 80 mg/kg/day, based on the default 

food factor of 0.05). Two control groups of 60 male and 60 female Wistar rats administered 

untreated basal diet. No interim sacrifice was conducted for this study. Two replicate studies 

were carried out.

No treatment-related effects were reported for clinical signs, mortality, or clinical pathology in 

male or female rats receiving any dose of the test material. The mortality rate for all groups was 

high. During the first year of treatment, 10-19% of males died while at the end on the study, 

only 26% of all rats remained alive. Pneumonia affected the majority of animals in all groups at 

various times during the study; antibiotic treatment was required during one episode. Absolute 

body weights presented graphically indicated that high-dose males and females weighed less 

than controls throughout most of the study. The magnitude of the reduction in absolute body 

weight could not be determined for assessment of statistical or toxicological significance. A 

15% reduction in body weight in high-dose females was observed at study termination. Food 

consumption was measured but not reported. 

Relative kidney weights were depressed in high-dose male rats, but no histopathological 

correlates were observed. Each animal was necropsied, but gross findings were not tabulated. 

Vacuolization of pancreatic acinar cells (generally slight or affecting only a few cells) was 

observed in 11 males and 13 females receiving the high-dose and in none of the controls of either 

sex. Only selected histopathological data were presented in the summary tables of the study 

report; therefore, a complete assessment of histopathological findings could not be conducted. 

No treatment-related neoplasms were reported; common neoplasms included pituitary adenomas 

and mammary fibro adenomas in female rats. The microscopic findings in the pancreatic acinar 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 42 of 57

cells were generally slight, affected only a few cells, and caused no physiological effect on 

glucose levels.

Based on the results of this study (decreased terminal body weight in females), the LOAEL 

for systemic toxicity was established at 80 mg/kg/day; a LOAEL was not established in

males. The NOAEL was established at 40 mg/kg/day in females at 80 mg/k/day in females.

This chronic toxicity/carcinogenicity study in the rat is Unacceptable/Guideline and does not 

satisfy the guideline requirement for a chronic toxicity/carcinogenicity oral study [OPPTS 

870.4300 (§83-5)] in the rat. There were numerous deficiencies in this study. The major 

deficiencies are listed as follows:

 The mortality rate for all groups was high, leaving only 25% or fewer animals in some 

groups out of an initial number of at least 80 per group.

 Respiratory infections were very prevalent in all groups and may have affected the 

outcome of the study.

 Summary tables were not available for clinical signs, body weights, body weight gains, 

food consumption, urinalysis data, and gross findings.

 Summary tables for microscopic findings were not complete, contained errors, and did 

not include the number of animals examined at each anatomical site.

 The data were not analyzed statistically.

 The evidence suggests that this study does not comply with GLP procedures.

870.4200b Carcinogenicity (feeding) – Mouse

In a carcinogenicity study (MRID 00020717) Tebuthiuron (>97% a.i., lot # B30-23-149) was 

administered to groups of 80 Harlan ICR mice/sex/dose in pelleted diet at dose levels of 400, 

800, or 1600 ppm (equivalent to 60, 120, or 240 mg/kg/day based on the default food factor of 

0.15) for 2 years. The control group, consisting of 120 males and 120 females was fed untreated 

pelleted diet. Animals were equally subdivided by dose and sex into two sub-studies; the second 

sub-study was started 1 week after the first. It should be noted that animals were not assigned by 

body weight. 

Although there was a statistically significant decrease (32.4 g, 12%) in the terminal body weights 

of high-dose females in one of the sub-studies (M9153), this is likely due to the higher body 

weight (36.7 g) of the control females in this sub-study. The terminal body weight of the control 

females in the other sub-study was 34.1 g.

There were no compound related effects on mortality, clinical signs, hematology or clinical 

chemistry, organ weights, or gross or microscopic pathology. 

The LOAEL for systemic toxicity was not established. The NOAEL was established at 

1600 ppm (240 mg/kg/day). 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 43 of 57

At the doses tested, there was no treatment related increase in tumor incidence when 

compared to that of controls. Dosing was not considered adequate based on the absence of 

systemic effects.

This carcinogenicity study in the mouse is Unacceptable/Guideline and does not satisfy 

guideline requirements for a carcinogenicity study [OPPTS 870.4200; OECD 451] in mice.

A.4.6 Mutagenicity 

Table A.4.6: Tebuthiuron Mutagenicity Studies

Study Results

870.5100

Bacterial reverse gene mutation 

assay

There was no increase in mutant frequency in tested bacterial strains exposed up to the 

limit dose (5000 μg/plate) with or without S9 activation.

870.5100

Bacterial reverse gene mutation 

assay

There was no increase in mutant frequency in any S. typhimurium or E. coli tested 

strain exposed to tebuthiuron (98.0%) with or without metabolic activation. There was 

no evidence of induced mutant colonies over background in tested S. typhimurium 

strains and E. coli strains with or without S9 activation. 

870.5300

In vitro mammalian cell gene 

mutation

In a mammalian cell gene mutation assay in vitro, cultures of mouse lymphoma were 

exposed to Tebuthiuron (98.0%) technical at concentrations limited by cytotoxicity.

Mutations were not induced at any concentration with activation. Tebuthiuron was 

considered weakly mutagenic but only in the absence of metabolic activation. No 

evidence of an increased mutant frequency was observed in the presence of metabolic 

activation.

870.5550

Unscheduled DNA synthesis in 

mammalian cell culture

In an unscheduled DNA synthesis assay, primary rat hepatocyte cultures were exposed 

to Tebuthiuron (99.1%) to the limit of cytotoxicity (900 μg/mL). UDS activity was 

evaluated at concentrations up to 800 μg/mL and there was no evidence of induction 

of UDS. There was no evidence that unscheduled DNA synthesis, as determined by 

radioactive tracer procedures [nuclear silver grain counts] was induced.

870.5375

In vitro mammalian cell 

chromosome aberration

In a mammalian chromosome aberration assay, Chinese Hamster Ovary (CHO) cell 

cultures were exposed to Tebuthiuron (99.08%) at concentrations limited by 

cytotoxicity. A significant increase in the percent of cells with aberrations was noted 

in nonactivated and activated cultures at cytotoxic doses. The predominant types of 

aberrations were chromosome and chromatid breaks. No significant increases were 

observed at lower concentrations; however, rare complex aberrations, such as 

triradials, quadriradials and complex rearrangements were noted, providing further 

support for clastogenicity. Positive control values were acceptable. There was 

evidence of an increase in structural chromosomal aberrations over background in the 

presence and absence of metabolic activation at cytotoxic doses.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 44 of 57

870.5915

In vivo sister chromatid 

exchange

In an in vivo cytogenetic assay measuring sister chromatid exchange (SCE) frequency 

in Chinese hamster bone marrow cells female Chinese hamsters (3/group) were 

administered single oral doses of tebuthiuron (99.1%, Lot No. 729AS7) in 10% 

aqueous acacia at 3000, 4000, or 5000 mg/kg. 

Tebuthiuron was tested up to cytotoxic concentrations. Hypo-activity was noted in all 

treatment groups and bone marrow cytotoxicity (as evidenced by an increase in the 

percent division metaphases) was observed at 5000 mg/kg. There was no increase in 

the number of cells containing SCEs compared to controls at any concentration of 

tebuthiuron tested. Cyclophosphamide (50 mg/kg) and vehicle control values were 

acceptable. There was no evidence of an increase in SCEs over background.

A.4.7 Neurotoxicity

870.6200 Acute Neurotoxicity Screening Battery- Rat

Waived by HASPOC.

870.6200 Subchronic Neurotoxicity Screening Battery -Rat

Waived by HASPOC.

A.4.8 Metabolism

870.7485 Metabolism – Rat

Terminal distribution data showed no significant amounts of residual radioactivity in any tissue 

examined, but the skin showed the highest amounts relative to other tissues. Excretion was rapid 

at both the low and high dose levels in both sexes, but was delayed during the first 12 hours postdose, indicating saturation of biotransformation or excretion. Six metabolites of tebuthiuron 

were identified. The major metabolite in 0-24 hour urine of male (58.3%) and female (62.1%) 

rats was identified as hydroxylated tebuthiuron metabolites (109-OH and /or 104-OH). The 

second most abundant metabolite was identified as metabolite 106 of tebuthiuron. This 

comprised between 9-15% of the administered dose in 0-24 hour urine of low dose rats, and 

between 1-10% of the administered dose in high dose rats. Two other metabolites identified, 

104/109 and 103-OH, comprised between 2-10% of the administered dose in male and female 0-

24 hour urine. Feces contained minor amounts of 104-OH and 109-OH, accounting for an 

average of 3.5% of the administered dose.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 45 of 57

A.4.9 Immunotoxicity

870.7800 Immunotoxicity- Rat

In an immunotoxicity study (MRID #48722705), Tebuthiuron (99.8 % a.i., Lot no. EQ 4821, 

TSN 100583) was administered to female Crl: WI (Han) (10/dose) in the diet at dose levels of 0, 

400, 1000, or 2000 ppm (equivalent to 0, 33.8, 84.9, and 148 mg/kg/day, respectively) for 29 

days. The positive control group (10 females) was administered 20 mg/kg bw/day of 

cyclophosphamide (10 mL/kg at a concentration of 5 mg/mL) by intraperitoneal injection from

study Days 24-28. During the study, clinical condition, bodyweight, food and water 

consumption, organ weight, and macroscopic pathology were evaluated. On the study Day 24, 

all animals in all groups received a single intravenous dose of sheep red blood cells (SRBC) (4 x 

108 SRBC/mL, 0.5 mL/animal). At sacrifice, selected organs were removed and weighed 

(kidney, liver, spleen and thymus). The anti-SRBC IgM response was measured with Enzyme 

Linked Immunosorbent Assay (ELISA).

There were no premature deaths and no treatment-related effects on clinical signs. Animals in 

2000 or 1000 ppm groups had treatment-related decreases in body weight, body weight gain and 

food consumption throughout the study. Animals in 2000 ppm group also had treatment related 

consistently higher reticulocyte counts than the control. There were statistically significant 

decreased in absolute and relative thymus weights; statistically significant increased relative liver 

weights; and statistically significant decreased in absolute kidney and spleen weights in this 

group. Positive control group treated with cyclophosphamide had statistically significant 

decreased in absolute and relative spleen and thymus weights. There was lower body weight 

gain from study Day 22-29, when compared to the vehicle control group; however, it was not 

statistically significant.

 The systemic LOAEL was 1000 ppm (equivalent to 84.9 mg/kg/day) based on decreased 

body weight and body weight gain. The systemic NOAEL was 400 ppm (equivalent to 33.8 

mg/kg/day).

There were no statistically significant differences observed in anti-SRBC IgM levels in treated 

groups when compare to the vehicle control group. High inter-individual variability was noted 

in all the treatment groups as well as in the control group. Evaluation of the individual animal 

data of this study did not show any trend or distribution that would demonstrate significant 

suppression of anti-SRBC antibody response. Positive control group had statistically significant 

decrease in the anti SRBC IgM levels. This confirmed the ability of the test system to detect 

immuno-suppressive effects and confirmed the validity of the study design.

The Natural Killer (NK) cells activity was not evaluated in this study. The toxicology database 

for tebuthiuron does not reveal any evidence of immunotoxicity. The overall weight of evidence 

suggests that the chemical does not directly target the immune system. Under HED guidance a 

NK cell activity assay is not required at this time.

 The NOAEL for immunotoxicity was 2000 ppm (equivalent to 148 mg/kg/day), the highest 

dose tested. The immunotoxicity LOAEL was not established.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 46 of 57

This immunotoxicity study is classified acceptable/guideline and satisfy the guideline

requirement for an immunotoxicity study (OPPTS 870.7800) in rats.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 47 of 57

Appendix B. Physical/Chemical Properties

Table B1: Chemical Identity of Tebuthiuron

Common Name Tebuthiuron

Chemical Name N-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-y1] N,N ’dimethyl urea

IUPAC 1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-1,3-dimethylurea

PC Code 105501

Chemical Abstracts Number 34014-18-1

Registration Review Case Number 0054

Chemical Structure

Table B2: Physico-Chemical Properties for Tebuthiuron

Parameter Value Reference

Molecular Weight 228.3 PubChem

Melting point/range 161 oC at 760 mm Hg

D256269, A. Smith, 06/29/1999

WSSA Herbicide Handbook 

Committee. Herbicide Handbook of 

the Weed Science Society of 

America, 6th Ed. WSSA, Champaign, 

IL. 1989.

pH NA: Solid at 25 oC

Water solubility 2.5 mg/mL

Solvent solubility (g/100mL)

25.0 in chloroform 0.37 in benzene

17.0 in methanol 7.0 in acetone

0.61 in hexane 6.0 in acetonitrile

Vapor pressure 2 x 10-6 mm Hg at 25 degrees Celsius

Chemical class/use Herbicide Urea carbamate

Soil Half-life 12 to 15 months w/40 in rainfall 1996 EXTOXNET

Partition-coefficient in noctanol / water Kow = log P 1.8 ; pH=7 at 25 C MSDS
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 48 of 57

Table B3: Summary of Metabolites and Degradates to be Included in the Risk Assessment and Tolerance Expression Followed 

by Chemical Structures in Figure A.

Matrix

Plants Primary 

Crop

Combined residues of the herbicide tebuthiuron (103): (N-(5- (1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-

N,N'-dimethylurea) and its metabolites, 103(OH): N-(5-(2-hydroxy-1,1-dimethylethyl)-1,3,4-thiadiazol-2-

yl)-N,N'-dimethylurea, 104: N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N-methylurea, and 109: N-(5-

(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N'-hydroxymethyl-N-methylurea.

Livestock Ruminant

Combined residues of the herbicide tebuthiuron (103): (N-(5-(1,1-dimethylethyl) -1,3,4-thiadiazol-2-yl)-

N,N'-dimethylurea) and its metabolites 104:N-(5-(1,1-dimethyl ethyl)-1,3,4-thiadiazol-2-yl)-N-methyl-urea, 

106: N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)urea, 108: 2-dimethylethyl-5-amino-1,3,4-thiadiazole, 

and 109:N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N'-hydroxymethyl-N-methylurea.

Milk

Combined residues of the herbicide tebuthiuron (103): (N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-

N,N'-dimethylurea) and its metabolites 104: N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N-methyl-urea, 

104 (OH): N-(5-(2-hydroxy-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N-methylurea, 106: N-(5-(1,1-

dimethylethyl)-1,3,4-thiadiazol-2-yl)urea, 109: N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N'-

hydroxymethyl-N-methylurea, and 109 (OH): N-(5-(2-hydroxy-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-

N'-hydroxymethyl-N-methylurea

Drinking Water Combined residues of the herbicide tebuthiuron (103): (N-(5- (1, 1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-

N,N'-dimethylurea) and its metabolites 104: N-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]- N-methy-lurea.

Table B.4:
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 49 of 57

The drinking water models and their descriptions are available at the EPA internet site: 

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

Table B5: Tebuthiuron EDWCs for the Wisconsin Corn Scenario in Groundwater

Drinking Water 

Source

(Model) 

Highest Daily Value

Acute

Post Breakthrough average 

Chronic

Average simulation 

Breakthrough 

Time 

 (μg/L) (μg/L) (days)

Groundwater 

(PRZM-GW) 2020* 1740 2230

*A time series water residue distribution was used in the acute dietary assessment.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 50 of 57

Appendix C. Residue Summary Table

Table C.1: International Residue Limits for Tebuthiuron (105501; 05-NOV-2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.390

(a) General (1) combined residues of the herbicide tebuthiuron (N-(5- (1,1-

dimethylethyl)-1,3,4-thiadiazol-2-yl)-N,N'-dimethylurea) and its metabolites N-(5-(2-

hydroxy-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N,N'-dimethylurea, N-(5-(1,1-

dimethylethyl)-1,3,4-thiadiazol-2-yl)-N-methylurea, and N-(5-(1,1-dimethylethyl)-

1,3,4-thiadiazol-2-yl)-N'-hydroxymethyl-N-methylurea

None None

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

US Canada Mexico1 Codex

Grass, forage 10.0

Grass, hay 10.0

(2) combined residues of the herbicide tebuthiuron (N-(5-(1,1-dimethylethyl) -1,3,4-

thiadiazol-2-yl)-N,N'-dimethylurea) and its metabolites N-(5-(1,1-dimethylethyl)-

1,3,4-thiadiazol-2-yl)-N-methylurea, N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-

yl)urea, 2-dimethylethyl-5-amino-1,3,4-thiadiazole, and N-(5-(1,1-dimethylethyl)-

1,3,4-thiadiazol-2-yl)-N'-hydroxymethyl-N-methylurea 

None None

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

US Canada Mexico1 Codex

Cattle, fat 1.0

Cattle, meat 1.0

Cattle, meat byproducts 5.0

Goat, fat 1.0

Goat, meat 1.0

Goat, meat byproducts 5.0

Horse, fat 1.0

Horse, meat 1.0

Horse, meat byproducts 5.0

Sheep, fat 1.0

Sheep, meat 1.0

Sheep, meat byproducts 5.0

US Canada Mexico1 Codex

(3) combined residues of the herbicide tebuthiuron (N-(5-(1,1-dimethylethyl)-1,3,4-

thiadiazol-2-yl)-N,N'-dimethylurea) and its metabolites N-(5-(1,1-dimethylethyl)-

1,3,4-thiadiazol-2-yl)-N-methylurea, N-(5-(2-hydroxy-1,1-dimethylethyl)-1,3,4-

thiadiazol-2-yl)-N-methylurea, N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)urea, 

N-(5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N'-hydroxymethyl-N-methylurea, 

and N-(5-(2-hydroxy-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl)-N'-hydroxymethyl-Nmethylurea 

None None

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

US Canada Mexico1 Codex

Milk 0.8

Completed: M. Negussie; 11/05/2013
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 51 of 57

Appendix D. Spray Drift

Table D.1: Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Tebuthiuron for the Dermal Route of Exposure

Crop/Rate 

Group

Spray Type/ 

Nozzle 

Configuration 

Applicatio

n Rate (lb 

ai/A)

Estimate

d or 

Adjusted 

TTR 

(ug/cm2)

At 

Edge 

10 

Feet 

25 

Feet 

50 

Feet 

75 

Feet 

100 

Feet 

125 

Feet 

150 

Feet 

200 

Feet 

250 

Feet 300 Feet 

Dermal 

MOE Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Dermal 

MOE 

Pastureland

Aerial

Fine to 

Medium

4 0.4446

36 45 55 72 95 120 150 170 230 270 330 

Medium to 

Coarse 44 60 81 110 160 210 270 320 440 580 720 

Coarse to Very 

Coarse 51 75 110 180 250 330 420 520 720 930 1,200 

AT401, M, 10 

mph, 37% SD 40 51 66 89 120 60 190 220 290 360 440 

WASP, M, 10 

mph, 37% SD 43 55 72 110 150 190 230 270 360 440 520 

AT401, C, 10 

mph, 25% SD 47 66 94 140 200 260 320 390 550 720 850 

WASP, C, 10 

mph, 25% SD 55 77 110 180 250 330 410 520 720 930 1,000 

AT401, VC, 10 

mph, 20% SD 53 81 130 210 300 410 520 670 930 1,200 1,600 

WASP, VC, 10 

mph, 20% SD 68 110 160 260 370 490 670 780 1,200 1,300 1,600 

Groundboom

High Boom 

Fine to 

Medium/Coarse

190 490 720 1,000 1,300 1,600 1,900 1,900 2,300 3,100 3,100 

Low Boom 

Fine to 

Medium/Coarse

280 780 1,200 1,600 1,900 2,300 3,100 3,100 4,700 4,700 4,700 

High Boom 

Fine to 

Medium/Coarse 6 0.6669

 

130 

 

330 

 

480 

 

690 

 

890 

 

1,000 

 

1,200 

 

1,200 

 

1,600 

 

2,100 

 

2,100 

Low Boom 

Fine to 

Medium/Coarse

 

190 

 

520 

 

780 

 

1,000 

 

1,200 

 

1,600 

 

2,100 

 

2,100 

 

3,100 

 

3,100 

 

3,100 

1. The AT401 is the representative fixed wing aircraft and the WASP is the representative helicopter. 
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 52 of 57

Table D.2: Children (1<2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Tebuthiuron for the Combined Dermal and Oral Routes of Exposure

Crop/Rate 

Group

Spray Type/ 

Nozzle 

Configuration 

Appli

cation 

Rate 

(lb 

ai/A)

Estimated 

or 

Adjusted 

TTRt

(ug/cm2)

At 

Edge 10 Feet 25 Feet 50 Feet 75 Feet 100 Feet 125 Feet 150 Feet 200 Feet 250 Feet 300 Feet 

Combin

ed 

MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Combine

d MOE 

Pastureland

Aerial

Fine to 

Medium

4 0.4446

 

18 

 

22 

 

27 

 

36 

 

47 

 

61 

 

73 

 

86 

 

110 

 

140 

 

160 

Medium to 

Coarse

 

22 

 

30 

 

40 

 

56 

 

80 

 

100 

 

130 

 

160 

 

220 

 

290 

 

360 

Coarse to Very 

Coarse

 

25 

 

37 

 

56 

 

87 

 

120 

 

160 

 

210 

 

260 

 

360 

 

460 

 

580 

AT401, M, 10 

mph, 37% SD

 

20 

 

25 

 

33 

 

44 

 

59 

 

77 

 

94 

 

110 

 

140 

 

180 

 

220 

WASP, M, 10 

mph, 37% SD

 

21 

 

27 

 

36 

 

54 

 

73 

 

94 

 

120 

 

140 

 

180 

 

220 

 

260 

AT401, C, 10 

mph, 25% SD

 

23 

 

33 

 

47 

 

69 

 

98 

 

130 

 

160 

 

190 

 

270 

 

360 

 

420 

WASP, C, 10 

mph, 25% SD

 

27 

 

38 

 

55 

 

87 

 

120 

 

160 

 

200 

 

260 

 

360 

 

460 

 

510 

AT401, VC, 10 

mph, 20% SD

 

26 

 

40 

 

64 

 

100 

 

150 

 

200 

 

260 

 

330 

 

460 

 

580 

 

770 

WASP, VC, 10 

mph, 20% SD

 

33 

 

52 

 

81 

 

130 

 

180 

 

240 

 

330 

 

380 

 

580 

 

660 

 

770 

Groundboom

High Boom 

Fine to 

Medium/Coarse

 

94 

 

240 

 

360 

 

510 

 

660 

 

770 

 

920 

 

920 

 

1,200 

 

1,500 

 

1,500 

Low Boom Fine 

to 

Medium/Coarse

 

140 

 

380 

 

580 

 

770 

 

920 

 

1,200 

 

1,500 

 

1,500 

 

2,300 

 

2,300 

 

2,300 

High Boom 

Fine to 

Medium/Coarse 6 0.6669

 

63 

 

160 

 

240 

 

340 

 

440 

 

510 

 

620 

 

620 

 

770 

 

1,000 

 

1,000 

Low Boom Fine 

to 

Medium/Coarse

 

93 

 

260 

 

380 

 

510 

 

620 

 

770 

 

1,000 

 

1,000 

 

1,500 

 

1,500 

 

1,500 

1. The AT401 is the representative fixed wing aircraft and the WASP is the representative helicopter.
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 53 of 57

Appendix E. Occupational Exposure Scenarios and Risk Estimates

Table E.1: Occupational Dermal Handler Non-Cancer Exposure and Risk Estimates for Tebuthiuron

Exposure Scenario Crop / 

Target 

Category

Application Rate2

Amount 

Handled / Area 

Treated3

Dermal Unit Exposures (ug/lb 

ai)1 Dermal Dose (mg/kg/day)4 Dermal MOE5

Formulation Application 

Equipment Value Units Value Units SL/No G

SL/G DL/G EC SL/No 

G

SL/G DL/G EC SL/No 

G

SL/G DL/G EC

Mixer/Loader

DF/WDG

Aerial Pastureland

Rangeland 4

lb ai/A

1200

acres

227 51.6 41.2 9.8 13.6 3.1 2.48 0.59 1 4.5 5.6 24

Groundboom 200 227 51.6 41.2 9.8 2.28 0.52 0.41 0.1 6.1 27 34 140

Groundboom Non-crop 

land 6 200 227 51.6 41.2 9.8 3.4 0.77 0.62 0.15 4.1 18 23 95

P/G

Aerial

Pastureland

Rangeland 4

1200

8.4 6.9 3.4 8.6 0.50 0.41 0.20 0.52 28 34 69 27

Non-crop 

land 6 8.4 6.9 3.4 8.6 0.76 0.62 0.31 0.77 19 23 46 18

Tractor-drawn 

spreader

Pastureland

Rangeland 4

200

8.4 6.9 3.4 8.6 0.08 0.07 0.03 0.09 170 200 410 160

Noncropland 6 8.4 6.9 3.4 8.6 0.13 0.10 0.05 0.13 110 130 270 110

Applicator

Spray

Aerial Pastureland

Rangeland 4

lb ai/A

1200

acres

2.08 0.13 110

Groundboom 200 78.6 16.1 12.6 5.1 0.79 0.161 0.126 0.05 18 87 110 270

Groundboom Non-crop 

land 6 200 78.6 16.1 12.6 5.1 1.18 0.24 0.19 0.08 12 58 74 180

P/G

Aerial

Pastureland

Rangeland 4

1200 1.7

0.10 140

Non-crop 

land 6 0.15 92

Tractor-drawn 

Spreader

Pastureland

Rangeland 4

200

9.9 7.2 4.2 2 0.1 0.072 0.04 0.02 140 190 330 700

Non-crop 

land 6 9.9 7.2 4.2 2 0.15 0.11 0.06 0.03 94 130 220 470

Hand dispersal Non-crop 

land and 

Rights-ofway 

0.00014 lb ai/ft2 10,000 ft2

104000 71000 40280 1.83 1.24 0.71 7.7 11 20

Shaker can 112 11.2 11.2 0.002 0.0002 0.0002 7100 71000 71000

Flagger

Spray

Aerial

Pastureland

Rangeland 4 lb ai/A

350 acres

11 12 10.6 0.19 0.21 0.185 73 67 76

P/G

2.75 2.73 1.59 0.05 0.05 0.03 290 290 500

Non-crop 

land 6 lb ai/A 2.75 2.73 1.59 0.072 0.07 0.04 190 200 330
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 54 of 57

Mixer/Loader/Applicator

DF/WDG

Backpack

Non-crop 

land and 

Rights-ofway 

1.6 lb 

ai/gallon

40 gallons

8260 8260 4120 6.61 6.61 3.3 2.1 2.1 4.2

Manuallypressurized 

Handwand

100000 430 365 80 0.34 0.293 0.18 41 48

Mechanicallypressurized 

Handgun

1000 gallons 1300 390 290 26 7.8 5.8 0.54 1.8 2.4

P/G

Belly grinder

6 lb ai/A

1

acres

10000 9300 5700 0.75 0.7 0.43 19 20 33

Rotary 

spreader 5 440 240 130 0.17 0.09 0.05 85 160 290

Cup 0.00014 lb ai/ft2 10,000 ft2 112 11.2 11.2 0.002 0.0002 0.0002 7100 71000 71000

Spoon 4170 3030 1580 0.07 0.05 0.03 190 260 510

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (May 2013); Level of mitigation: Dermal baseline PPE includes no gloves, long sleeved shirt, long pants, socks plus shoes. The addition 

of gloves and double layer protection is included in the far right column for comparison. Eng. Controls (EC) assumes enclosed cockpits for the aerial and ground application of tebuthiuron for all formulations. Shaded out cells 

are not applicable to scenario or there is no dermal unit exposure data.

2 Based on registered labels (Table 3.2.1).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ 80 (kg). 

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 55 of 57

Table E.2: Occupational Inhalation Handler Non-Cancer Exposure and Risk Estimates for Tebuthiuron 

Exposure Scenario Crop / 

Target 

Category

Application Rate2

Amount 

Handled / Area 

Treated3

Inhalation Unit Exposures 

(ug/lb ai)1 Inhalation Dose (mg/kg-day)4

Inhalation MOE5

Formulation Application 

Equipment Value Units Value Units NoR

PF5 

R

PF10 

R

EC No-R PF5 R PF10 R EC No-R PF5 R PF10 

R

EC

Mixer/Loader

DF/WDG

Aerial Pastureland

Rangeland 4

lb ai/A

1200

acres

8.96 1.79 0.9 0.24 0.54 0.11 0.05 0.014 26 130 260 970

Groundboom 200 8.96 1.79 0.9 0.24 0.09 0.018 0.009 0.002 160 780 1600 5800

Groundboom Non-crop 

land 6 200 8.96 1.79 0.9 0.24 0.14 0.03 0.01 0.004 100 520 1000 3900

P/G

Aerial

Pastureland

Rangeland 4

1200

1.7 0.34 0.17 0.08 0.10 0.02 0.010 0.005 140 690 1400 2800

Non-crop 

land 6 1.7 0.34 0.17 0.08 0.15 0.03 0.02 0.01 92 460 920 1900

Tractor-drawn 

Spreader

Pastureland

Rangeland 4

200

1.7 0.34 0.17 0.08 0.02 0.003 0.002 0.0008 820 4100 8200 17000

Non-crop 

land 6 1.7 0.34 0.17 0.08 0.03 0.01 0.002 0.001 550 2700 5500 11000

Applicator

Spray

Aerial Pastureland

Rangeland 4

lb ai/A

1200

acres

0.005 0.0003 48000

Groundboom 200 0.34 0.07 0.03 0.04 0.003 0.0007 0.0003 0.0004 4100 21000 41000 33000

Groundboom Non-crop 

land 6 200 0.34 0.07 0.03 0.04 0.005 0.001 0.0005 0.0006 2700 14000 27000 22000

P/G

Aerial

Pastureland

Rangeland 4

1200

1.3 0.08 180

Non-crop 

land 6 1.3 0.12 120

Tractor-drawn 

Spreader

Pastureland

Rangeland 4

200

1.2 0.24 0.12 0.22 0.01 0.002 0.001 0.002 1200 5800 12000 6400

Non-crop 

land 6 1.2 0.24 0.12 0.22 0.02 0.004 0.002 0.003 780 3900 7800 4200

Hand 

dispersal

Non crop 

land and 

Rights-ofway 

0.00014 lb ai/ft2 10,000 ft2

470 94 47 0.008 0.002 0.0008 1700 8500 17000

Shaker can 12.5 2.5 1.25 0.0002 0.00004 0.00002 64000 320000 640000

Flagger

Spray

Aerial

Pastureland

Rangeland 4

lb ai/A 350 acres

0.35 0.07 0.04 0.006 0.001 0.0006 2300 11000 23000

P/G

Pastureland

Rangeland 4 0.15 0.03 0.02 0.004 0.001 0.0004 5300 27000 53000

Non-crop 

land 6 0.15 0.03 0.02 0.004 0.001 0.0004 3600 18000 36000

Mixer/Loader/Applicator

DF/WDG Backpack 1.6 40 gallons 2.58 0.52 0.26 0.002 0.0004 0.0002 6800 34000 68000
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 56 of 57

Manuallypressurized 

Handwand

Non-crop 

land and 

Rights-ofway

lb 

ai/gallon

30 6 3 0.02 0.005 0.002 580 2900 5800

Mechanicallypressurized 

Handgun

1000 gallons 3.9 0.78 0.39 0.08 0.02 0.01 180 900 1800

P/G

Belly grinder

6 lb ai/A

1

acres

62 12.4 6.2 0.005 0.001 0.0005 3000 15000 30000

Rotary 

spreader 5 10 2 1 0.004 0.0008 0.0004 3700 19000 37000

Cup 0.00014 lb ai/ft2 10000 ft2 12.5 2.5 1.25 0.0002 0.00004 0.00002 64000 320000 640000

Spoon 121 24.2 12.1 0.002 0.0004 0.0002 6600 33000 66000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (May 2013); Level of mitigation: Inhalation baseline PPE includes no respirator. The addition of PF5, PF10 respirators on handlers is 

included in the far right column for comparison. Eng. Controls included enclosed cockpits for the aerial application of tebuthiuron for all formulations. Shaded out cells are not applicable to scenario or there is no inhalation unit 

exposure data.

2 Based on registered labels (Table 3.2.1).

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ 80 (kg).

5 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Tebuthiuron Human Health Risk Assessment DP No. 414218

Page 57 of 57

Table E.3: Occupational Dermal and Inhalation Handler ARI Risk Estimates for Tebuthiuron1

Exposure Scenario

Crop / Target 

Category Application Rate2

Amount Handled 3 ARI4

Formulation application equipment Value Units SL/No G 

+ No-R

SL/G + 

No-R

SL/G + 

PF5 R

DL/G + 

PF5 R

SL/G + 

PF10 R

DL/G 

+ PF10 

R

EC

Mixer/Loader

DF/WD

G

Aerial Pastureland/Rangeland 4 lb ai/A 1,200

acres

0.01 0.02 0.03 0.04 0.04 0.05 0.19

Groundboom 200 0.04 0.1 0.2 0.24 0.23 0.28 1.1

Groundboom Non-crop land 6 lb ai/A 200 0.03 0.06 0.13 0.16 0.15 0.19 0.76

P/G

Aerial Pastureland/Rangeland 4 lb ai/A 1,200 0.09 0.1 0.2 0.35 0.27 0.46 0.25

Non-crop land 6 lb ai/A 0.06 0.07 0.15 0.23 0.18 0.31 0.16

Tractor-drawn Spreader

Pastureland/Rangeland 4 lb ai/A

200

0.55 0.58 1.3 2.1 1.6 2.7 1.5

Non-crop land 6 lb ai/A 0.37 0.39 0.88 1.4 1.1 1.8 1

Applicator

Spray

Aerial Pastureland/Rangeland 4 lb ai/A 1,200

acres

1.1

Groundboom 200 0.17 0.72 0.84 1 0.85 1.1 2.5

Groundboom No-crop land 6 lb ai/A 200 0.11 0.48 0.56 0.7 0.57 0.72 1.7

P/G

Aerial Pastureland/Rangeland 4 lb ai/A 1,200 0.16

Non-crop land 6 lb ai/A 0.11

Tractor-drawn Spreader Pastureland/Rangeland 4 lb ai/A 200 0.65 0.74 1.4 2.1 1.6 2.6 3.3

Non-crop land 6 lb ai/A 0.43 0.49 0.98 1.4 1.1 1.7 2.2

Hand dispersal

Rights-of-Way 0.00014 lb ai/ft2 10,000 ft2

0.07 0.1 0.11 0.2 0.11 0.2

Shaker can 34 59 220 220 340 340

Flagger

Spray

Aerial

Pastureland/Rangeland 4 lb ai/A 350 acres

0.55 0.52 0.63 0.71 0.65 0.74

P/G Pastureland/Rangeland 1.9 1.9 2.6 4.2 2.7 4.6

Non-crop land 6 lb ai/A 1.2 1.3 1.8 2.8 1.9 3

Mixer/Loader/Applicator

DF/WD

G

Backpack

Non-crop land, and 

Rights-of-way (e.g., 

utilities, railroad, 

roadways)

1.6 lb ai/gallon

40

gallons

0.02 0.02 0.02 0.04 0.02 0.04

Manually-pressurized 

Handwand 0.002 0.24 0.36 0.41 0.38 0.44

Mechanicallypressurized Handgun 1,000 0.005 0.02 0.02 0.02 0.02 0.02

P/G

Belly grinder 6 lb ai/A 1

acres

0.18 0.19 0.2 0.32 0.2 0.33

Rotary spreader 5 0.69 1.1 1.5 2.5 1.5 2.7

Cup 0.00014 lb ai/ft2 10,000 ft2 34 59 220 220 340 340

Spoon 1.5 1.9 2.4 4.4 2.5 4.7

1 Refer back to previous table 9.1.1. and 9.1.2 for “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ([May 2013]); Level of mitigation: Dermal baseline (long sleeve shirt, pants, shoes plus socks), 

dermal baseline plus gloves, and dermal double layer plus gloves, Inhalation baseline (no respirator), PF5 respirator, and PF10 respirator. Eng. Controls (EC) included enclosed cockpits for the aerial application of tebuthiuron for 

all formulations. Shaded out cells are not applicable or no unit exposure data

2 Based on registered labels (Table 3.2.1).

3 Exposure Science Advisory Council Policy #9.1.

4 ARI = Aggregate Risk Index = 1÷ [(Dermal LOC (100) ÷ Dermal MOE) + (Inhalation LOC (1000) ÷ Inhalation MOE)]