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) re quested that the Health Eff ects Division (HED) conduct an occupational exposure and risk assessment fo r 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 ingred ient (ai), imazosulfuron, via the end use product (E P), 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 fi rst food use of imazosulfuron. This document was reviewed by the HED Exposure Science Advisory Council (ExpoSAC) on 07/08/2010.

Page 1 of 9Page 2 of 9 1.0 EXECUTIVE SUMMARY

Imazosulfuron, V-10142 Ag Herbicide (V-10142), is a sulfonylurea herbicid e 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-emerge nt application in toma toes and rice, and postemergent/soil-directed application in peppers. The mode of herbic idal action is the inhibition of the acetolactate synthase (ALS) enzyme. In addition to the pr oposed uses addressed in this memo, there is a pending applica tion for registration for use of imazosulfuron on established turf grass in residential and recreati onal areas including golf courses, as well as around established landscape ornamentals, conifers including Chri stmas 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 wate r dispersible granule (WDG). This granular

formulation is to be added to wa ter, resulting in a dispersion of finely divided herbicide particles suspended in water to be applied for weed control.

This document assesses occupational and resident ial 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 prio r to crop planting (pre-emergent) and shortly following new crop plantings (post-emergent). A pplications to peppers may only be made to well established peppers (at least 10 inches tall). Application timing ma y also vary depending on the target weed (pre-emergence or post-emergen ce 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, pe ppers, 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 intermed iate-term occupational exposure to imazosulfuron during mixing, loading, applying, and other handling ac tivities. Additionally, there is a potential for short- and intermediate-term occupational exposure during postapplication activities. Chronic exposure is not expect ed for the proposed use pattern.

Hazard Characterization Dermal endpoints were not selected for imazo sulfuron 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 reproduc tion study and a co-critical 90- day oral toxicity study in rats. Since no inhalation absorp tion data are available, toxicity by the

inhalation route is consid ered to be equivalent to the estimat ed 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, clin ical 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 interspeci es extrapolation and 10X for intraspecies variation].Page 3 of 9 Imazosulfuron is classified as “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor increases in two adequate rodent carcinogenic ity 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 Hand lers Exposure Database (PHED) Version 1.1 as presented in PHED Surrogate Exposure Guide (Es timates of Worker Exposure from the Pesticide Handler Exposure Database Version 1.1, A ugust 1998) to assess handler exposures for regulatory actions when chemi cal-specific monitoring data ar e not available (HED ExpoSAC Standard Operating Procedure (SOP) No. 7, dated 01/28/1999).

All handler scenarios (mixer/loaders, flaggers, an d 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 re spirator) for any of the handler

scenarios.

The minimum level of personal protective equi pment (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 exposur e can occur via the dermal and/ or inhalation route. Dermal exposure during postapplication activities is not c onsidered because applicable dermal endpoints were not identified. Based on the Agency's current practices, a quantitative occupational postapplication inhalation exposure assessment wa s not performed for imazosulfuron at this time. If new policies or proce dures are put into place, the Agen cy may revisit the need for a quantitative occupational postapplication inhala tion exposure assessment for imazosulfuron.

The imazosulfuron technical material has been cl assified in Toxicity Category III for acute dermal and Toxicity Category IV for primary eye irritation and primary sk in irritation. Per the WPS, a 12-hr restricted entry interval (REI) is required for ch emicals 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).Page 4 of 9 Review of Human Research This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pest icide or other chemical. Thes e studies, which comprise PHED, have been determined to require a review of thei r ethical conduct, and have received that review.

2.0 HAZARD CHARACTERIZATION

Table 1 presents a summary of the appli cable endpoints select ed for imazosulfuron.

Table 1. Summary of Toxicological Do se 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 do se and the primary toxi c 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 quan titative risk assessment for this r oute and duration is not necessary.

Inhalation Shortand IntermediateTerm (1-30 days) NOAEL= 235 mg/kg/day (MRID 47305232)

(100% absorption) UF A = 10X

UF H = 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 en vironmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intrasp ecies). FQPA SF = FQPA Safety Factor. LOC = level of concern. MOE = margin of exposure.

A summary of the acute toxicity categories for the technical ma terial 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 LD 50 >5000 mg/kg IV

870.1200 Acute Dermal- Rat 47305227 LD 50 >2000 mg/kg III

870.1300 Acute Inhalation- Rat 47305228 LC 50 >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/A3.0 PROPOSED USE PATTERN

Imazosulfuron belongs to the sulf onylurea class of herbicides. Imazosulfuron has no currently registered food uses. The proposed use of imazo sulfuron 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-emerg ent) and shortly following new cr op plantings (post-emergent). Applications to peppers may only be made to we ll 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 applicati on may be made per season for all three crops: tomatoes, peppers, and rice. The application ra tes 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 Pa ttern 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 ae rial equipment. The application methods, maximum application rates, and use sites are su mmarized in Table 3. Th ere is potential for exposure to imazosulfuron during mixing, loading, a nd applying activities. Handler exposure is expected to be short- or inte rmediate-term based on information provided on the proposed label.

The quantitative exposure and risk assessment developed for occupationa l 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 aeri al application,

Applying 3) sprays with groundboom equipment,

Page 5 of 9Page 6 of 9 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 handli ng activities were not submitted to the Agency in support of this Sectio n 3 application. It is HED policy to use data from PHED Version 1.1 to assess handler expos ures for regulatory actions when chemicalspecific data are not available (H ED 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 w ith groundboom equipment,

- 1200 acres for applying with aerial equipment, and

- 1200 acres for flagging for aerial application.

Application Rate Maximum application rates for all pr oposed uses are shown in Table 3.

Body Weight The average adult body weight of 70 kg was used fo r estimating the intermediate-term inhalation

dose since the short- and intermediate-term toxi cological endpoints of concern are not based on developmental effects.

Absorption Factor Inhalation toxicity e ndpoints of concern were id entified 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-ter m inhalation endpoint was based on an oral study and no inhalation absorption data are av ailable, toxicity by the inhalation route is considered to be equivalent to the estimate d 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,Page 7 of 9 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 occupatio nal handlers for each exposure

route. All MOE values were calcu lated 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 co mbined in this assessment, since shortand intermediate-term dermal toxi city 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-sp ecies 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 gr eater than or equal to 100 ar e not of concern to HED.

Short- and intermediate-term dermal toxicity en dpoints 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 base d on a two-generation reproduction study and a co-critical 90-day oral to xicity study in rats. The MOEs range from 59,000 (mixing/loading to support aerial applic ation) to 930,000 (applying with groundboom equipment). These risk estimates are not of concern to HED.

Summaries of the inhalation risk estimates fo r 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.Page 8 of 9 Table 4. Short- and Intermediate-T erm Occupational Handler Exposu re and Risk for Imazosulfuron.

Exposure Scenario Crop or Target App

Rate a (lb ai/A) Acres

Treated Daily b Baseline

Inhalation

Unit Exposure c (mg/lb ai) Short- and

IntermediateTerm Dose (mg/kg/day)

Inhalation d Short- and

IntermediateTerm MOE

Inhalation e

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 Do se (mg/kg/day) = daily unit e xposure (mg/lb ai) x applic ation 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 quant itative occupational pos tapplication inhalation exposure assessment was not performed for imazosu lfuron at this time. However, there are multiple potential sources of postapplication i nhalation exposure to individuals performing postapplication activities in previously treate d fields. These potential sources include volatilization of pestic ides and resuspension of dusts and/or pa rticulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilizati on of pesticides from its Federal Insecticide, Fungici de, and Rodenticide Act Scientif ic Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SA P/meetings/2009/120109meeting.html ) and is in the process of evaluating the SAP report as well as available po stapplication inhalation exposure data generated by the Agricultural Reentry Task Force. The Ag ency may, as appropriate, develop policies and procedures to identify the need for and, subs equently, the way to in corporate occupational postapplication inhalation exposure into the Agen cy's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational postapplication inhalation exposur e assessment for imazosulfuron.Page 9 of 9 The imazosulfuron technical material has been cl assified in Toxicity Category III for acute dermal and Toxicity Category IV for primary eye irritation and primary sk in irritation. Per the WPS, a 12-hr REI is required for chemicals clas sified 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 th is time; therefore, no residential handler or postapplication exposure and risk assessments have been conducted in this document.

Residential Bystander Posta pplication Inhalation Exposure Based on the Agency's current practices, a qua ntitative postapplication inhalation exposure assessment was not performed for imazosulfuron at this time. Howe ver, volatilization of pesticides may be a potential source of postappli cation inhalation exposure to individuals nearby to pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticid es 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 appr opriate, develop policies and procedures to identify the need for and, s ubsequently, the way to in corporate postapplication inhalation exposure into the Agency 's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need fo r a quantitative postapplic ation inhalation exposure

assessment for imazosulfuron.

Spray Drift Spray drift is always a potential source of expos ure to residents nearby to spraying operations. This is particularly the case with aerial appl ication, but, to a lesser ex tent, could also be a potential source of exposure from the ground application method employed for imazosulfuron. The Agency has been working with the Spray Dr ift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide regulation and ot her parties to develop the best spray drift management practices. The Agency is now re quiring interim mitigation measures for aerial applications that must be placed on product la bels/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 de veloping a policy on how to appr opriately 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 tu rf and does not result in exposures of concern. It is unlikely that spray drift would result in a hi gher potential for risk of expos ure than the scenarios already

assessed.