UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM

DATE: July 9, 2010 

SUBJECT: Imazosulfuron. Occupational and Residential Exposure Assessment for 

Proposed Use on Tomatoes, Peppers (Bell and Non-Bell), and Rice. 

PC Code: 118602 DP Barcode: D367021

Decision No.: 406200 Registration No.: 59639-RLL, 59639-RLU (technical)

Petition No.: NA Regulatory Action: Section 3

TXR No.: NA CAS No.: 122548-33-8

MRID No.: NA 40 CFR: §180.XXX

 

FROM: Nancy J. Tsaur, Chemist 

Risk Assessment Branch 3 (RAB3) 

Health Effects Division (7509P) 

THROUGH: Barry O’Keefe, Senior Biologist, ORE Team Leader 

Risk Assessment Branch 3 (RAB3) 

Health Effects Division (7509P) 

TO: Sheila Healy, Toxicologist, Risk Assessor 

Risk Assessment Branch 3 (RAB3) 

Health Effects Division (7509P) 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

occupational exposure and risk assessment for the new proposed uses of imazosulfuron on 

tomatoes, peppers (bell and non-bell), and rice. This document assesses occupational and 

residential exposures and risks from the proposed uses of the herbicide active ingredient (ai), 

imazosulfuron, via the end use product (EP), V-10142 Ag Herbicide (EPA Reg. No. 59639-

RLL). This assessment also covers the proposal to register the technical product, imazosulfuron 

(EPA Reg. No. 59639-RLU), because this is the first food use of imazosulfuron. This document 

was reviewed by the HED Exposure Science Advisory Council (ExpoSAC) on 07/08/2010. 

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1.0 EXECUTIVE SUMMARY 

Imazosulfuron, V-10142 Ag Herbicide (V-10142), is a sulfonylurea herbicide active ingredient 

(ai) proposed for a first food use registration in the United States for control of sedges and 

selected broadleaf weeds by pre- and post-emergent application in tomatoes and rice, and postemergent/soil-directed application in peppers. The mode of herbicidal action is the inhibition of 

the acetolactate synthase (ALS) enzyme. In addition to the proposed uses addressed in this 

memo, there is a pending application for registration for use of imazosulfuron on established turf 

grass in residential and recreational areas including golf courses, as well as around established 

landscape ornamentals, conifers including Christmas trees, and on bare ground in non-crop areas 

(DP#348001, S. Healy, 03/13/2009). 

V-10142 is to be formulated as a 75% ai water dispersible granule (WDG). This granular 

formulation is to be added to water, resulting in a dispersion of finely divided herbicide particles 

suspended in water to be applied for weed control. 

This document assesses occupational and residential exposures and risks from the proposed use 

of imazosulfuron on tomatoes, peppers, and rice. 

Proposed Use Profile

V-10142 may be applied to tomatoes and rice prior to crop planting (pre-emergent) and shortly 

following new crop plantings (post-emergent). Applications to peppers may only be made to 

well established peppers (at least 10 inches tall). Application timing may also vary depending on 

the target weed (pre-emergence or post-emergence weeds). However, only one application may 

be made per season for all three crops: tomatoes, peppers, and rice. The application rates range 

from 0.2 lb ai/A to 0.3 lb ai/A for tomatoes, peppers, and rice. Soil-directed ground application 

is to be used for all three crops; aerial application is permitted for rice only. 

Exposure Potential from Proposed Uses

There is a potential for short- and intermediate-term occupational exposure to imazosulfuron 

during mixing, loading, applying, and other handling activities. Additionally, there is a potential 

for short- and intermediate-term occupational exposure during postapplication activities. 

Chronic exposure is not expected for the proposed use pattern.

Hazard Characterization

Dermal endpoints were not selected for imazosulfuron because no systemic toxicity was 

observed at the limit dose in the dermal study; there was no significant evidence of increased 

sensitivity or susceptibility; and dermal absorption is expected to be minimal. The short-term 

inhalation endpoint was selected from a two-generation reproduction study and a co-critical 90-

day oral toxicity study in rats. Since no inhalation absorption data are available, toxicity by the 

inhalation route is considered to be equivalent to the estimated toxicity by the oral route of 

exposure (100% absorption) and is compared to the parental NOAEL of 235 mg/kg/day. The 

endpoint includes mortality, clinical signs, and decreased body weights, body weight gain, and 

food consumption at the LOAEL of 892 mg/kg/day. The level of concern (LOC) is a margin of 

exposure (MOE) less than 100 [10X for interspecies extrapolation and 10X for intraspecies 

variation]. 
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Imazosulfuron is classified as “Not likely to be Carcinogenic to Humans” based on the absence 

of significant tumor increases in two adequate rodent carcinogenicity studies; therefore, cancer 

risk was not assessed. 

Occupational Exposure and Risk

Agricultural Handler Risk 

Chemical-specific handler exposure data were not submitted in support of this registration. It is 

HED policy to use data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as 

presented in PHED Surrogate Exposure Guide (Estimates of Worker Exposure from the Pesticide 

Handler Exposure Database Version 1.1, August 1998) to assess handler exposures for 

regulatory actions when chemical-specific monitoring data are not available (HED ExpoSAC 

Standard Operating Procedure (SOP) No. 7, dated 01/28/1999). 

All handler scenarios (mixer/loaders, flaggers, and applicators) resulted in margins of exposure 

(MOEs) greater than the level of concern (i.e. the LOC is an MOE < 100). The inhalation risk 

estimates to handlers are not of concern to HED at baseline (no respirator) for any of the handler 

scenarios. 

The minimum level of personal protective equipment (PPE) for handlers is based on acute 

toxicity for the end-use product. RD is responsible for ensuring that PPE listed on the label is in 

compliance with the Worker Protection Standard (WPS) for Agricultural Pesticides. 

Agricultural Postapplication Risk 

Occupational postapplication exposure can occur via the dermal and/or inhalation route. Dermal 

exposure during postapplication activities is not considered because applicable dermal endpoints 

were not identified. Based on the Agency's current practices, a quantitative occupational 

postapplication inhalation exposure assessment was not performed for imazosulfuron at this 

time. If new policies or procedures are put into place, the Agency may revisit the need for a 

quantitative occupational postapplication inhalation exposure assessment for imazosulfuron. 

The imazosulfuron technical material has been classified in Toxicity Category III for acute 

dermal and Toxicity Category IV for primary eye irritation and primary skin irritation. Per the 

WPS, a 12-hr restricted entry interval (REI) is required for chemicals classified under Toxicity 

Category III or IV. The proposed label indicates a 12-hour REI, which complies with the WPS. 

Residential Exposure and Risk

This document only presents the assessment of the proposed new agricultural use of 

imazosulfuron on tomatoes, peppers, and rice. No residential uses and no occupational uses at 

residential sites are being requested in this petition; therefore, a residential risk assessment was 

not conducted. Residential exposure and risk was previously assessed and were not of concern; 

for residential handlers, MOEs ranged from 2,600,000 to 32,000,000, and for children, the 

combined short-term postapplication incidental oral MOE was 17,000 on the day of application 

(DP#349707, K. O’Rourke, 02/17/2009). 
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Review of Human Research

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

intentionally exposed to a pesticide or other chemical. These studies, which comprise PHED, 

have been determined to require a review of their ethical conduct, and have received that review. 

2.0 HAZARD CHARACTERIZATION 

Table 1 presents a summary of the applicable endpoints selected for imazosulfuron. 

Table 1. Summary of Toxicological Dose and Endpoints for Imazosulfuron. 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/

FQPA 

Safety 

Factors 

RfD, PAD, 

LOC for 

Risk 

Assessment 

Study and Toxicological Effects 

Dermal Short- and 

Intermediate-Term 

(1-30 days) 

No systemic toxicity occurred at the limit dose and the primary toxic effects of concern 

(liver, eye) were adequately assessed in a 21-day dermal toxicity study (MRID 47305236). 

It is concluded that this compound is not absorbed or is poorly absorbed through the skin 

and, therefore, a quantitative risk assessment for this route and duration is not necessary. 

Inhalation Shortand IntermediateTerm (1-30 days) 

NOAEL= 235 

mg/kg/day 

(MRID 

47305232) 

(100% 

absorption) 

UFA= 10X 

UFH= 10X 

LOC is 

MOE < 100 

Reproduction, 2 generation (rat; MRID 

47305304) and 90-day oral toxicity (rat; 

47305232). 

LOAEL = 892 mg/kg/day based on 

mortality, clinical signs, decreased body 

weights, body weight gains and food 

consumption in parents (MRID 

47305304). LOAEL = 956 mg/kg/day 

based on decreased body weight gains and 

food efficiency (MRID 47305232). 

Cancer (oral, 

dermal, inhalation) 

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of 

significant tumor increases in two adequate rodent carcinogenicity studies (MRID 

47305307, mouse; 47305306, rat). 

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

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

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

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

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

of concern. MOE = margin of exposure. 

A summary of the acute toxicity categories for the technical material are included in Table 2. 

Table 2. Acute Toxicity of Imazosulfuron Technical.

Guideline No. Study Type MRID# Results Tox Cat

870.1100 Acute Oral- Rats 47305221 LD50 >5000 mg/kg IV 

870.1200 Acute Dermal- Rat 47305227 LD50 >2000 mg/kg III 

870.1300 Acute Inhalation- Rat 47305228 LC50 >2.12 mg/L IV 

870.2400 Acute Eye Irritation- Rabbit 47305229 Non-irritating IV 

870.2500 Primary Dermal Irritation- Rabbit 47305230 Non-irritating IV 

870.2600 Dermal Sensitization- Guinea pig 47305231 Negative N/A 
3.0 PROPOSED USE PATTERN 

Imazosulfuron belongs to the sulfonylurea class of herbicides. Imazosulfuron has no currently 

registered food uses. The proposed use of imazosulfuron is for control of sedges and selected 

broadleaf weeds on tomatoes, peppers, and rice. V-10142 may be applied to tomatoes and rice 

prior to crop planting (pre-emergent) and shortly following new crop plantings (post-emergent). 

Applications to peppers may only be made to well established peppers (at least 10 inches tall). 

Application timing may also vary depending on the target weed (pre-emergence or postemergence weeds). However, only one application may be made per season for all three crops: 

tomatoes, peppers, and rice. The application rates range from 0.2 lb ai/A to 0.3 lb ai/A for 

tomatoes, peppers, and rice. Soil-directed ground application is to be used for all three crops; 

aerial application is permitted for rice only. 

The proposed uses of V-10142 (EPA Reg. No. 59639-RLL) are summarized in Table 3. 

Table 3. Proposed Use Pattern for Imazosulfuron.

Crop

Treatment 

Type/Target of 

Application 

Application 

Equipment 

Maximum 

Application 

Rate 

(lb ai/A)

Treatment 

Interval Preharvest Interval 

V-10142 Ag Herbicide, EPA Reg. No. 59639-RLL, WDG 75% ai

Tomatoes Soil-Directed Spray Groundboom 0.3 1 application 

per year 21 days 

Peppers 

(Bell and Non-Bell) Soil-Directed Spray Groundboom 0.3 1 application per year 21 days 

Rice Soil-Directed Spray, 

Flooded Fields 

Groundboom 

or Aerial 0.3 1 application per year 

Application may be 

made up until 2 inch 

internode stage of rice. 

4.0 OCCUPATIONAL EXPOSURE/RISK PATHWAY 

4.1 Handler Exposure 

Imazosulfuron may be applied using ground or aerial equipment. The application methods, 

maximum application rates, and use sites are summarized in Table 3. There is potential for 

exposure to imazosulfuron during mixing, loading, and applying activities. Handler exposure is 

expected to be short- or intermediate-term based on information provided on the proposed label. 

The quantitative exposure and risk assessment developed for occupational handlers is based on 

the following exposure scenarios: 

Mixing/Loading

1) WDG (dry flowable) formulations to support groundboom application, 

2) WDG (dry flowable) formulations to support aerial application, 

Applying

3) sprays with groundboom equipment, 

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4) sprays with aerial equipment, and 

Flaggers

5) flagging for aerial application. 

4.1.1 Data and Assumptions for Handler Exposure Scenarios 

Unit Exposures

Chemical-specific data for assessing exposure during pesticide handling activities were not 

submitted to the Agency in support of this Section 3 application. It is HED policy to use data 

from PHED Version 1.1 to assess handler exposures for regulatory actions when chemicalspecific data are not available (HED ExpoSAC, SOP No.7, January 1999). 

Area Treated

Based on HED ExpoSAC SOP No. 9.1, the area treated in a day was assumed to be: 

- 80 acres for mixing/loading to support groundboom applications, 

- 1200 acres for mixing/loading to support aerial applications, 

- 80 acres for applying with groundboom equipment, 

- 1200 acres for applying with aerial equipment, and 

- 1200 acres for flagging for aerial application. 

Application Rate

Maximum application rates for all proposed uses are shown in Table 3. 

Body Weight

The average adult body weight of 70 kg was used for estimating the intermediate-term inhalation 

dose since the short- and intermediate-term toxicological endpoints of concern are not based on 

developmental effects. 

Absorption Factor

Inhalation toxicity endpoints of concern were identified for all durations of exposure. However, 

because long-term exposures are not anticipated, only short- and intermediate-term inhalation 

risks were assessed. Since the short- and intermediate-term inhalation endpoint was based on an 

oral study and no inhalation absorption data are available, toxicity by the inhalation route is 

considered to be equivalent to the estimated toxicity by the oral route of exposure (100% 

absorption).

Equations and Calculations

Daily Dose: Daily dose (inhalation) was calculated by normalizing the daily inhalation exposure 

value by body weight and accounting for inhalation absorption. 

Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x {Absorption Factor (%/100)} 

 Body Weight (kg) 

 Where: 

 Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg 

pesticide active ingredient/kg body weight/day), 

 Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for 

dermal absorption or amount inhaled that is available for inhalation absorption, 
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 Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as 

the skin or lungs, and 

 Body Weight = Body weight determined to represent the population of interest in a risk 

assessment. 

Margin of Exposure (MOE): The daily inhalation dose received by handlers was compared to the 

appropriate PoD (i.e. NOAEL) to assess the risk to occupational handlers for each exposure 

route. All MOE values were calculated using the following formula: 

MOE = NOAEL (mg/kg/day) 

 ADD (mg/kg/day) 

Where: 

 MOE = Margin of exposure value used by HED to represent risk or how close a chemical exposure 

is to being a concern (unitless), 

 ADD = Average daily dose is absorbed dose received from exposure to pesticide, and 

 NOAEL = Dose level in a toxicity study, where no observed adverse effects occurred in the study. 

Combined Risks: Dermal and inhalation risks were not combined in this assessment, since shortand intermediate-term dermal toxicity endpoints were not identified. 

4.1.2 Handlers Exposure and Risk 

The LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. 

HED applies a 10X factor to account for inter-species extrapolation and a 10X factor to account 

for intra-species sensitivity. The total uncertainty factor that has been applied to the non-cancer 

risk assessment for imazosulfuron is 100X for occupational exposure. Occupational exposure 

and risk resulting in MOEs greater than or equal to 100 are not of concern to HED. 

Short- and intermediate-term dermal toxicity endpoints were not identified because no systemic 

toxicity was seen at the limit dose in a 21-day dermal toxicity study in rabbits. 

To determine the short- and intermediate-term risks, daily inhalation exposures (assuming 100% 

absorption) were compared to the NOAEL of 235 mg/kg/day based on a two-generation 

reproduction study and a co-critical 90-day oral toxicity study in rats. The MOEs range from 

59,000 (mixing/loading to support aerial application) to 930,000 (applying with groundboom 

equipment). These risk estimates are not of concern to HED.

Summaries of the inhalation risk estimates for occupational handlers are included in Table 4. 

The maximum application rate for each exposure scenario is presented as the worst case 

scenario. The inhalation risks to handlers are not of concern to HED for any of the handler 

scenarios.
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Table 4. Short- and Intermediate-Term Occupational Handler Exposure and Risk for Imazosulfuron. 

Exposure Scenario Crop or Target 

App 

Ratea

(lb ai/A)

Acres 

Treated 

Dailyb

Baseline 

Inhalation 

Unit 

Exposurec

(mg/lb ai) 

Short- and 

IntermediateTerm Dose 

(mg/kg/day) 

Inhalationd

Short- and 

IntermediateTerm MOE 

Inhalatione

Mixer/Loader 

Mixing/Loading Dry 

Flowables for 

Groundboom 

Applications

Tomatoes, Peppers 

(Bell and Non-Bell), Rice 0.3 80 0.00077 0.000264 890,000 

Mixing/Loading Dry 

Flowables for Aerial 

Applications

Rice 0.3 1200 0.00077 0.00396 59,000 

Applicator 

Applying Sprays via 

Groundboom 

Equipment 

Tomatoes, Peppers 

(Bell and Non-Bell), Rice 0.3 80 0.00074 0.000254 930,000 

Applying Sprays via 

Aerial Equipment Rice 0.3 1200 0.000068 0.000350 670,000 

Flagger 

Applying Sprays for 

Aerial Equipment Rice 0.3 1200 0.00035 0.000180 130,000 

a Application Rates based on proposed uses on label for V-10142 (EPA Reg. No. 59639-RLL). 

b Exposure Science Advisory Council Policy No. 9.1. 

c Unit Exposures based on PHED Version 1.1. 

d Short- and Intermediate-Term Inhalation Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre) x 

acres treated / body weight (70 kg). 

e Short- and Intermediate-Term Inhalation MOE = NOAEL (235 mg/kg/day) / inhalation daily dose (mg/kg/day). LOC = 100. 

4.2 Postapplication Exposure 

Based on the Agency's current practices, a quantitative occupational postapplication inhalation 

exposure assessment was not performed for imazosulfuron at this time. However, there are 

multiple potential sources of postapplication inhalation exposure to individuals performing 

postapplication 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. The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html) and is in the process of 

evaluating the SAP report as well as available postapplication inhalation exposure data generated 

by the Agricultural Reentry Task Force. The Agency 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 

postapplication inhalation exposure assessment for imazosulfuron. 
Page 9 of 9 

The imazosulfuron technical material has been classified in Toxicity Category III for acute 

dermal and Toxicity Category IV for primary eye irritation and primary skin irritation. Per the 

WPS, a 12-hr REI is required for chemicals classified under Toxicity Category III or IV. The 

proposed label indicates a 12-hour REI, which complies with the WPS. 

5.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK PATHWAY 

No residential uses are being requested at this time; therefore, no residential handler or 

postapplication exposure and risk assessments have been conducted in this document. 

Residential Bystander Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative postapplication inhalation exposure 

assessment was not performed for imazosulfuron at this time. However, volatilization of 

pesticides may be a potential source of postapplication inhalation exposure to individuals nearby 

to 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. The Agency received the SAP’s final report 

on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html) and is 

in the process of evaluating the SAP report. The Agency may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate postapplication 

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

into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure 

assessment for imazosulfuron. 

Spray Drift

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

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

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

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

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

management practices. The Agency is now requiring interim mitigation measures for aerial 

applications that must be placed on product labels/labeling. The Agency has completed its 

evaluation of the new data base submitted by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, 

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray drift management practices to reduce off-target drift and risks associated 

with aerial as well as other application types where appropriate. Note that imazosulfuron is 

directly applied to residential turf and does not result in exposures of concern. It is unlikely that 

spray drift would result in a higher potential for risk of exposure than the scenarios already 

assessed.