IMAZOSULFURON Human Health Risk Assessment DP No. D409228 

UN ITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: February 15,2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Imazosulfuron: Human Health Risk Assessment for Proposed Uses on Melon 

(Crop Subgroup 9A) and Tuberous and Corm Vegetables (Crop Subgroup lC). 

PC Code: 118602 

Decision No.: 464490 

Petition No.: 2£8025 

DP Barcode: 409228 

Registration No.: 59639- 154 & 59639-166 

Regulatory Action: Section 3 Registration 

Risk Assessment Type: Single Chemical/ Aggregate Case No.: None 

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

MRID No.: NA 40 CFR: 180.651 

FROM: Sheila Healy, Toxicologis~ IJ(ff _l 

Steve Funk, Chemist .,( ~ ;;:;:..JtCassi Walls, Biologist ~ ;t.L.>J2.9h 

Risk Assessment Branch III 

Health Effects Division (7509P) 

THROUGH: Christine Olinger, Chief Jfof 

Risk Assessment Branch I 

Health Effects Division (7 , ) 

TO: Barbara Madden/Andrew Ertman (RM 05) 

Risk Integration, Minor Use & Emergency Response Branch 

Registration Division (7505P) 

Page 1 of 37 
IMAZOSULFURON Human Health Risk Assessment DP No. 0409228 

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

2.0 HED Recommendations ................................................ ....................... ............................. 6 

2.1 Data Deficiencies ... .................. ............................................................................... ........ 6 

2.2 Tolerance Considerations .......................................... ....... .... ......................................... 6 

2.2.1 Enforcement Analytical Method ............... ............... .... ............................................. 6 

2.2.2 International Harmonization ........................................................................ .... .... .... . 7 

2.2.3 Recommended Tolerances ......... ... .... .... ........ ............ .... ....... ........ .............................. 7 

2.2.4 Revisions to Petitioned-For Tolerances .................................................. .... .... ......... . 7 

2.3 Label Recommendations .... .... ... .... .... ............... ........ ......... ........... .................................. 7 

3.0 Introduction ... ....... .... ... ...................... .... ............................................................................. 7 

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

3.2 PhysicaVChemical Characteristics ................. ........ ................ ..................... ... ..... ....... .. 8 

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

3.4 Anticipated Exposure Pathways ......... .... ...................................................................... 9 

3.5 Consideration of Environmental Justice ...................................................................... 9 

4.0 Hazard Characterization and Dose-Response Assessment .......................................... I 0 

4.1 Summary of Toxicological Effects .............................................................................. I 0 

4.2 Safety factor for Infants and Children (FQPA Safety Factor) ................................ II 

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

4.2.2 Evidence of Neurotoxicity ........................................................................................ 12 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal.. ..... . 12 

4.2.4 Residual Uncertainty in the Exposure Database ......................... .................... ...... 12 

4.3 Toxicity Endpoint and Point of Departure Selections .............................................. 13 

5.0 Dietary Exposure and Risk Assessment ................................... ...................................... 15 

5.1 Residues of Concern Summary and Rationale .......................................................... 15 

5.2 Food Residue Profile ..... ........... ............... ..................................................................... I5 

5.3 Water Residue Profile ............................................................................................. .... . 16 

5.4 Dietary Risk Assessment .. .... .... ... .... .... ....................... ........ .......................................... I7 

5.4.1 Description of Residue Data Used in Dietary Assessment .. ................................ .. I7 

5.4.2 Percent Crop Treated Used in Dietary Assessment ........ ...................................... 17 

5.4.3 Acute Dietary Risk Assessment ................................................................. .... .... ..... . I 7 

5.4.4 Chronic Dietary Risk Assessment .......... ... .............................................................. 17 

5.4.5 Cancer Dietary Risk Assessment.. .............. ................... .......................................... 18 

5.4.6 Summary Table ........................................................................................... .............. 18 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 19 

6.1 Residential Handler Exposure ... ................... .... ........ ....... ........................................... 19 

6.3 Combined Exposure ................................................................... .... .... ........ .... .............. 21 

6.4 Residential Bystander Postapplication Inhalation Exposure ................................... 21 

6.5 Spray Drift ................................... ........... ........ .... .... .... ............ .... .................................. 2I 

7.0 Aggregate Exposure/Risk Characterization ............................ .... .... ........ ............. .... .... . 22 

7.1 Acute Aggregate Risk. ............. ............... .... .... ........ .... .... .............................................. 22 

7.2 Short- and Intermediate-Term Aggregate Risk .............. .... .... .... ................ .... .......... 22 

7.3 Chronic Aggregate Risk ................ .... ................ .......................................................... 22 

7.4 Cancer Aggregate Risk ......................................................... ........ ........ .... ........ ........... 23 

8.0 Cumulative Exposure/Risk Characterization ..... ... ....................................................... 23 

9.0 Occupational Exposure/Risk Characterization .. ........ ............... .... ........ .... ............. ...... 23 

Page 2 of37 
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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9.1 Short- and Intermediate-Term Handler Risk ........................................................... 24

9.2 Short- and Intermediate-Term/ Post-Application Risk............................................ 25

9.2.1 Dermal Postapplication Risk ................................................................................... 25

9.2.2 Inhalation Postapplication Risk .............................................................................. 25

10.0 References......................................................................................................................... 26

Appendix A. Toxicology Profile and Executive Summaries .................................................. 27

A.1 Toxicology Data Requirements................................................................................... 27

A.2 Toxicity Profiles............................................................................................................ 28

Appendix B. Physical/Chemical Properties............................................................................. 33

Appendix C. Review of Human Research................................................................................ 34

Appendix D. Metabolism Summary Table .............................................................................. 35
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

Page 4 of 37

1.0 Executive Summary

Use Profile 

Imazosulfuron(2-chloro-N-[[4,6-dimethoxy-2-pyrimidinyl)-amino]carbonyl]imidazo[1,2-

a]pyridine-3-sulfonamide), a sulfonylurea herbicide, is currently registered for use on

agricultural crops including tomatoes, peppers and rice in addition to ornamentals and 

established turf grass in residential and recreational areas. Valent has proposed that the use on 

the following crops be added to the V-10142 Ag Herbicide label: melon crop subgroup 9A 

(citron melon, muskmelon, cantaloupe, and watermelon) and tuberous and corm vegetables crop 

subgroup 1C (arracacha, arrowroot, Chinese artichoke, Jerusalem artichoke, edible canna, bitter 

and sweet cassava, chayote, chufa, taro, ginger, leren, potato, sweet potato, tanier, turmeric, yam 

bean, and true yam). 

Imazosulfuron (V-10142) is formulated as a 75% ai water-dispersible granule (WG). 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. Imazosulfuron may be applied up to

twice a year to tuberous and corm vegetables prior to crop planting (pre-emergent) and shortly 

following new crop plantings (post-emergent). However, only one application per year may be 

made to well established melon plants (at least 5 inches wide). Application timing may vary 

depending on the target weed (pre-emergence or post-emergence weeds). The application rates 

range from 0.15 lb ai/A to 0.3 lb ai/A for melons and tuberous and corm vegetables. For the 

proposed uses, V-10142 Ag Herbicide may be applied with ground or handheld spray equipment.

Hazard Assessment

Chronic studies in the rat and dog indicate that liver is the primary target organ for chronic oral 

exposure. Mild to moderate thyroid effects were apparent only in the chronic toxicity study in 

dogs and adverse eye effects were observed in rats fed > 1000 mg/kg beginning at 3 months in 

the chronic toxicity/carcinogenicity study. Decreased body weight and body weight gain 

compared to control was a frequent finding throughout the toxicology database for 

imazosulfuron. 

Metabolism studies in the rat indicate that imazosulfuron is extensively absorbed, metabolized 

and excreted. 

In a 21-day dermal toxicity study in rats, no localized dermal or systemic effects were seen at the 

limit dose of 1000 mg/kg/day, the dermal and systemic NOAEL. There was no evidence of 

increased susceptibility in the submitted toxicology database. There is no concern for increased 

susceptibility to offspring following pre- and postnatal exposure to rats or in utero exposure in 

rabbits. Neither the rat nor rabbit developmental studies identified developmental effects. 

The genotoxic potential of imazosulfuron has been assessed as negative by several in vitro and in

vivo mutagenicity studies. The two-year combined chronic toxicity and carcinogenicity study in 

rats, as well as the 18-month carcinogenicity study in mice, showed no evidence of 

carcinogenicity. Imazosulfuron is classified as “not likely to be carcinogenic to humans,” based 

on the absence of significant tumor increases attributed to treatment.
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Imazosulfuron is not acutely toxic or irritating to the skin or eyes and is not a dermal sensitizer.

The data for imazosulfuron support a reduction of the FQPA safety factor to 1X.

Dietary Exposure 

The residue chemistry data and environmental fate data are adequate to assess human exposure. 

The chronic dietary food exposure assessment is conservative. The assessment is based on 

reliable data and will not underestimate exposure/risk.

Acute: An unrefined dietary assessment was conducted assuming that 100% of crops with the 

requested uses of imazosulfuron are treated and that all treated crops contain residues at 

tolerance level. In addition, default processing factors were assumed for the requested crop uses. 

Potential residues in drinking water were included in the analyses based on surface water results 

from the Tier I Rice Model. No population subgroups exceed HED’s level of concern at the 95th

percentile of exposure for food and drinking water. The U.S. population occupied < 1.0% of the 

acute population-adjusted dose (aPAD), while the most highly exposed population subgroup, all 

infants (< 1 year old), occupied 1.2% of the aPAD. 

Chronic: An unrefined chronic dietary assessment was conducted assuming that 100% of crops 

with the requested uses of imazosulfuron are treated and that all treated crops contain residues at 

tolerance level. In addition, default processing factors were assumed for the requested crop uses. 

Potential residues in drinking water were included in the analyses based on surface water results 

from the Tier I Rice Model. No population subgroups exceed HED’s level of concern for dietary 

exposure from food and drinking water: the U.S. population occupied < 1% of the chronic 

population-adjusted dose (cPAD), while the most highly exposed population subgroup, all 

infants (< 1 year old), occupied 2.0% of the cPAD. 

Residential Exposure 

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

uses that have been reassessed to reflect updates to HED’s 2012 Residential SOPs along with 

policy changes for body weight assumptions. Residential handler scenarios resulted in margins 

of exposure (MOEs) greater than the level of concern (i.e. the LOC is an MOE < 100) and 

therefore are not of concern to HED. The residential combined short-term post-application 

incidental oral scenario for children resulted in an MOE greater than the LOC of 100 and 

therefore is not of concern to HED.

Aggregate Risk

Aggregate acute risk is equivalent to acute dietary risk via food and drinking water exposure 

pathways and comprises 1.2% of the aPAD for the most highly exposed population, infants < 1 

year old. Likewise, chronic dietary risk comprises 2.0% of the cPAD for the most highly 

exposed population, infants < 1 year old.

Short- and Intermediate Term: There is potential short- and intermediate-term exposure to 

imazosulfuron via the dietary pathway (which is considered background exposure) and the 

residential pathway (which is considered the primary pathway). Since no dermal hazard was 

identified, the exposure pathways for adults include only the dietary and inhalation (residential 
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

Page 6 of 37

handler) routes. For children, the exposure pathway includes the dietary exposure and the 

incidental oral post-application residential pathway.

All aggregate MOEs are greater than 100; therefore, aggregate exposure is not of risk concern.

Occupational Exposure/Risk

Dermal exposure during handling activities was not considered because no systemic toxicity was 

observed at the limit dose in the dermal study. The occupational handler exposure and risk 

estimates indicate that short- and intermediate-term non-cancer inhalation MOEs are not of 

concern to HED (i.e., MOEs > 100) at baseline (no respirator) attire.

Dermal exposure during post-application activities was not considered because no systemic 

toxicity was observed at the limit dose in the dermal study. Based on the Agency's current 

practices, a quantitative occupational post-application 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 post-application inhalation exposure 

assessment for imazosulfuron.

Environmental Justice Considerations 

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

human health risk assessment. Dietary and non-dietary exposures were considered.

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 (listed in Appendix C) have 

been determined to require a review of their ethical conduct, and one of these studies is also 

subject to review by the Human Studies Review Board. All of the listed studies have received 

the appropriate review.

2.0 HED Recommendations

HED has examined the toxicology and residue chemistry database for imazosulfuron. There are 

no toxicology or residue chemistry issues that would preclude granting a registration for the 

requested uses of imazosulfuron or establishment of tolerances for residues of imazosulfuron as 

indicated in 2.2.3

2.1 Data Deficiencies

There are no outstanding data deficiencies or conditions of registration that would preclude the 

establishment of the tolerances outlined in this document.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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An adequate high performance liquid chromatography method with tandem mass spectroscopy 

detection (LC/MS/MS), Method RM-42C-3, is available for tolerance enforcement in plant 

commodities. The method determines residues of imazosulfuron and metabolite UDPM, or (4,6-

dimethoxy-pyrimidin-2-yl)-urea. The method has been adequately validated by an independent 

laboratory for the determination of imazosulfuron. A modification of the enforcement method 

was used for data collection in the melon and potato field trials. The method was adequately 

validated using control potato samples and cantaloupe fortified with imazosulfuron. The lowest 

level of method validation (LLMV) for residues of imazosulfuron in/on potato tubers, each 

processed fraction and cantaloupe was 0.02 ppm. Metabolite UDPM was not analyzed but is not 

required for potato based on the metabolism study where <1% TRR was reported to be present in 

potato (D367019, S. Funk, 10/18/2010). UDPM was up to 30% TRR in other metabolism 

studies and may be conservatively estimated at 30% of the imazosulfuron concentration in 

melons for purposes of dietary risk assessment.

2.2.2 International Harmonization

There are currently no established Codex, Canadian, or Mexican maximum residue limits 

(MRLs) established for imazosulfuron. 

2.2.3 Recommended Tolerances

It is recommended that tolerances be established for residues of the herbicide imazosulfuron (2-

chloro-N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]imidazo-[1,2-α]pyridine-3-

sulfonamide), including its metabolites and degradates, in or on the plant commodities specified 

below in Table 2.2.3. Compliance with the tolerance levels specified below is to be determined 

by measuring only imazosulfuron, or 2-chloro-N-[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]imidazo-[1,2-α]pyridine-3-sulfonamide. 

Table 2.2.3. Tolerance Summary for Imazosulfuron

Commodity

Proposed 

Tolerance (ppm)

Recommended 

Tolerance 

(ppm)

Comments; Correct Commodity 

Definition

Melon crop subgroup 9A 0.02 0.02 Melon subgroup 9A

Tuberous and corm vegetables crop 

subgroup 1C.

0.02 0.02 Vegetable, tuberous and corm, 

subgroup 1C

2.2.4 Revisions to Petitioned-For Tolerances

There are no revisions the tolerance petition (Table 2.2.3).

2.3 Label Recommendations

HED does not have any additional label recommendations regarding application to proposed 

crops or occupational or residential assessments.

3.0 Introduction
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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3.1 Chemical Identity

Table 3.1. Imazosulfuron Nomenclature.

Chemical structure

Common name Imazosulfuron

Company experimental name V-10142; TH-913

IUPAC name 1-(2-chloroimidazo[1,2-α]pyridin-3-ylsulfonyl)-3-(4,6-dimethoxypyrimidin-2-

yl)urea

CAS name 2-chloro-N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]imidazo-

[1,2-α]pyridine-3-sulfonamide

CAS registry number 122548-33-8

End-use product (EP) 75% WG (V-10142 Ag Herbicide; EPA Reg. No. 59639-166)

Chemical Class Sulfonylurea

3.2 Physical/Chemical Characteristics

The physicochemical properties of the technical grade of imazosulfuron are summarized in 

Appendix C. The log of the octanol/water partition coefficient is -0.07 at neutral pH, which 

indicates a lack of fat solubility and therefore no propensity to bioaccumulate in fatty tissue or 

milk. The low coefficient also suggests low dermal absorption. The Henry’s Law constant for 

imazosulfuron was determined to be 1.67×10-3Pa·m

3

/mol and the vapor pressure,< 6.3x10-4Pa at 

25oC). Imazosulfuron is soluble in water (429 mg/L at 20°C) which suggests dissipation of 

imazosulfuron in the environment is expected to occur predominantly via runoff and leaching. 

Considering abiotic degradation, imazosulfuron is photolyzed at pH 7 in water (t1/2 = 3.5 days). 

Under the field conditions in the soil, the calculated half-life values of imazosulfuron are 9.5 

days for first application and 15.2 to 75.3 days following the second application.

3.3 Pesticide Use Pattern

Table 3.3. Summary of Directions for Use of Imazosulfuron.

Applic. Timing, 

Type, and Equip.

Formu

-lation

Applic. 

Rate

(lbai/A)

Max.No. 

Applic/

Season

Max.Rate/

Season (lb 

ai/A)

PHI

(days)

 

 Use Directions and Limitations

Melon crop subgroup 9A (citron melon; muskmelon (cantaloupe); watermelon

N

N

N

N

N

H

N

H

S

O

O

Cl

O

CH3

O

CH3

O
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table 3.3. Summary of Directions for Use of Imazosulfuron.

Applic. Timing, 

Type, and Equip.

Formu

-lation

Applic. 

Rate

(lbai/A)

Max.No. 

Applic/

Season

Max.Rate/

Season (lb 

ai/A)

PHI

(days)

 

 Use Directions and Limitations

Row middle 

application 1 

(between rows) for 

plastic or bare soil 

culture)

75% 

WDG

0.19-0.3 1 0.3 48 Apply at any time during the cropping season 

(up to 48 days before harvest) as long as the 

melons are well established and at least 5 inches 

wide.

Avoid contact with the melon crop. When 

application is being made to melons grown in 

plastic mulch culture, adjust equipment to 

prevent the spray from contacting the plastic.

Vegetable, tuberous and corm, subgroup 1C (arracacha; arrowroot; artichoke, Chinese; artichoke, Jerusalem; canna, edible; 

cassava, bitter and sweet; chayote (root); chufa; dasheen (taro); ginger; leren; potato; sweet potato; tanier; turmeric; yam bean; 

yam, true)

2

Preemergence 

75% 

WDG

0.19 to 0.3

45

Apply to a well- prepared moist seedbed after 

planting to emergence or immediately after 

hilling.

Postemergence 0.15 to 

0.19

Apply after emergence if weeds are <3 inches 

in height as part of a weed program.

Sequential 

Application 

(Preemergence 

application 

followed early 

postemergence 

application)

3

.

0.15

Followed 

by

0.15

2 0.3 Apply to a well-prepared moist seedbed after 

planting to emergence or immediately after 

hilling.

The postemergence application must not be 

made any sooner than 21 days after the 

preemergence application. Emerged weeds 

must be under 3 inches in height.

1

For ground middle application, determine the area to be sprayed and calculate the amount of V-10142 AG herbicide and water 

needed based on a broadcast total spray volume of 20-40 gallons of water/A and the herbicide rate of 0.2-0.3 lb ai/A. Ensure 

thorough, uniform coverage.

2On potato, use a broadcast spray volume of 20-40 gallons water per acre. Do not apply by air. Make only 2 applications per 

year.

3Use of adjuvant is recommended only in the 2nd (postemergence) spray. 

 A 12 hr. reentry interval is required.

3.4 Anticipated Exposure Pathways

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

proposed new uses of imazosulfuron on all of the registered and proposed agricultural, 

commercial, and residential use sites. Humans may be exposed to imazosulfuron in food and 

drinking water, since imazosulfuron may be applied directly to growing crops and application 

may result in imazosulfuron reaching surface and ground sources of drinking water. There are 

also residential uses of imazosulfuron, so there is likely to be exposure in residential or nonoccupational settings. In an occupational setting, applicators may be exposed while handling the 

pesticide prior to application, as well as during application. There is also a potential for postapplication exposure for workers re-entering treated fields. This risk assessment considers all of 

the exposure pathways based on the registered and proposed new uses of imazosulfuron.

3.5 Consideration of Environmental Justice

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 
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to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/environmentaljustice/resources/policy/exec_order_12898.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’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

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.

4.0 Hazard Characterization and Dose-Response Assessment

Hazard characterization of imazosulfuron has been detailed previously in Imazosulfuron: 

Human Health Risk Assessment for Proposed Uses on Rice, Peppers and Tomatoes. D362653, S. 

Healy, 03-NOV-2010. This assessment includes summaries of the prior assessment. Since the 

last risk assessment, an acceptable/guideline immunotoxicity study has been submitted and the 

inhalation study requirement has been waived (TXR 0056566).

4.1 Summary of Toxicological Effects

Imazosulfuron is a selective herbicide which inhibits the plant enzyme acetolactate synthase 

(ALS). ALS is required to synthesize the essential, branched-chain amino acids, valine, leucine 

and isoleucine. ALS inhibitors exhibit low mammalian toxicity, likely due to the fact that 

mammals lack acetolactate synthase.

Metabolism studies in the rat indicate that imazosulfuron is extensively absorbed, metabolized 

and excreted. The majority of the dose was recovered in the urine (~66%) and a substantial 

amount was isolated in the feces (~33%). Almost all radioactivity isolated in the feces was 

absorbed and excreted in the bile. Thus, the test compound was nearly completely absorbed and 

near total excretion (96% administered dose) was achieved by 48 hours post-dose. There were 

no notable sex-differences in the excretion profile. At 72 hours post-dose, only 0.25% of the 

administered dose was detected in the gastrointestinal contents, organs, tissues and residual 

carcass. Of this residual radioactivity, label was detected only in the kidney (0.045 μg equiv/g), 

plasma (0.044 μg equiv/g), and liver (0.036 μg equiv/g); levels in other organs and tissues were 

less than 0.020 μg equiv/g. These data indicate that imazosulfuron does not bioaccumulate at 

this low dose level of 5 mg/kg. Five metabolites were identified and accounted for 

approximately 75% of the administered dose. HMS was the major metabolite detected in both 
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Page 11 of 37

urine and feces. Metabolic reactions included demethylation, hydroxylation of the pyrimidine 

ring, methylation or glucuronidation of the hydroxyl group, and opening of the pyrimidine ring 

and formation of guanidine. A dermal absorption study of imazosulfuron is not available; 

however it is pertinent to note that dermal hazard was not identified in the toxicology database.

The toxicity database for imazosulfuron suggests that this herbicide possesses relatively low 

toxicity. Many of the effects of single or repeated dosing are observed near or beyond the 

respective limit doses. The primary target organ of imazosulfuron toxicity was the liver in all 

species tested. Mild to moderate thyroid effects were apparent only in the chronic toxicity study 

in dogs. Dramatic eye effects (retinal degeneration, lens vascularization, cataracts and corneal 

scarring) were observed in rats fed > 1000 mg/kg beginning at 3 months in the chronic 

toxicity/carcinogenicity study. Ocular effects, increased incidence of eye opacity, corneal 

edema, inflammation and neovascularization, were also observed in the high-dose males (4577 

mg/kg/day) of the 90-day feeding toxicity study in rats. Decreased body weight and body weight 

gain compared to control was a frequent finding throughout the toxicology database for 

imazosulfuron.

Clinical signs observed in males at the limit dose of the acute neurotoxicity study (i.e., decreased 

motor activity, abnormal gait, upward curvature of the spine and piloerection at the limit dose 

can be attributed to generalized toxicity and were resolved by Day 2 of the study. No neurotoxic 

effects were observed during the subchronic screening battery or noted as clinical signs in any 

other repeat-dose study.

While ≥ 60% mortality was observed at 500 mg/kg/day and abortion (1/5, not treatment-related) 

at 250 mg/kg/day in a dose range-finding study in rabbits, no developmental effects were 

observed at 125 mg/kg/day (highest dose tested) in the guideline study. No developmental or 

reproductive toxicity was observed in the one-generation rat study. Decreased pup viability was 

observed in the rat two-generation reproduction study at a dose approaching the limit dose 

(LOAEL = 892 mg/kg/day) in both the F1 and F2 offspring generations. Mortality was also 

observed in the parental generation at this dose. No qualitative or quantitative offspring 

susceptibility was apparent in any of the submitted studies for imazosulfuron.

Review of acceptable carcinogenicity and mutagenicity studies provides no indication that 

imazosulfuron is a carcinogen, mutagen or clastogen.

Study summaries of the acute, subchronic and chronic toxicity and genotoxicity for 

imazosulfuron are provided in Appendix A.

4.2 Safety factor for Infants and Children (FQPA Safety Factor)

There is an adequate toxicity database for imazosulfuron and exposure data are complete or are 

estimated based on data that reasonably account for potential exposures. There is no evidence of 

susceptibility following in utero and/or postnatal exposure in the developmental toxicity studies 

in rats or rabbits, or in the 2-generation rat reproduction study. There are no residual 

uncertainties concerning pre- and postnatal toxicity and no neurotoxicity concerns. The chronic 

dietary (food and drinking water) exposure assessments are conservative. The dietary and 
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residential assessments are based on reliable data and will not underestimate exposure/risk. 

Based on these data and conclusions, the FQPA Safety Factor can be reduced to 1X.

4.2.1 Completeness of the Toxicology Database

The toxicology database is complete for imazosulfuron.

4.2.2 Evidence of Neurotoxicity

There is no indication that imazosulfuron is a neurotoxic chemical based on clinical observations 

of neurotoxicity during the conduct of developmental or chronic studies. No adverse 

neurobehavioral signs were observed at doses approaching the limit dose in any of the short-term 

studies (subchronic oral, 21-day dermal). No neurotoxic effects were observed during the 

subchronic neurotoxicity screen in which adverse effects of decreased body weight, body weight 

gain and food efficiency were observed at 575 mg/kg/day (LOAEL). The acute neurotoxicity 

screen (ACN) yielded a LOAEL at the limit dose for clinical signs, abnormal gait, decreased 

activity, piloerection and upward curvature of the spine and decreased motor activity in males, 

all of which were resolved by Day 2. No treatment-related effects were observed in Functional 

Observational Battery (FOB) parameters, gross and neurohistopathology, motor activity or brain 

morphometrics of the ACN. The weight of evidence demonstrates that imazosulfuron is not a 

neurotoxic compound because the clinical findings in the ACN study occurred only at the limit 

dose and may be attributed to generalized toxicity. A developmental neurotoxicity study is not 

required at this time.

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

There was no evidence of increased susceptibility in the submitted toxicology database. There is 

no concern for increased susceptibility to offspring following pre- and postnatal exposure to rats 

or in utero exposure in rabbits. Neither the rat nor rabbit developmental studies identified 

developmental effects. The parental NOAEL is clearly defined, less than or equal to the 

offspring NOAEL and based on general systemic toxicity. At near-limit dose, 20% - 30% 

decreases in numbers of implants/dam, total pups/dam and live pups/dam on PND 0, and 

viability index were observed in F1 pups of the 2-generation reproductive study in rats. 

Similarly, decreased live pups/dam and live births and viability and lactation indices were noted 

for F2 pups. The points of departure are protective of these effects.

4.2.4 Residual Uncertainty in the Exposure Database

The chronic dietary assessment conducted with DEEM-FCIDTM was an unrefined analysis. The 

assessment utilized tolerance level residues for all crops. In addition, default processing factors 

were assumed for all commodities. One hundred percent crop treated was assumed for all 

commodities. The dietary analysis also assumed that all drinking water will contain 

imazosulfuron at the highest chronic estimated drinking water concentration (EDWC) levels 

modeled by EFED for ground water or surface water. For these reasons it can be concluded that 

the DEEM-FCIDTM analysis does not underestimate risk from chronic exposure to 

imazosulfuron.
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Data have been previously requested to confirm the metabolic profile of pyrimidine-labeled 

imazosulfuron in rice grain in the confined rotational crop trial and to characterize field 

accumulation. A grain (wheat) rotational crop study is needed to identify maximum levels of 

residues in grain and livestock feed items (forage, straw) as a function of the plantback interval. 

On an interim basis, a plantback interval of 12 months is being imposed for grains and soybeans. 

The results of the rotational crop study may allow a shorter plantback interval. The confined 

rotational crop study showed that imazosulfuron and metabolites will be negligible (<0.01 ppm) 

on forage, hay, straw, stover, and grain at a 365 day plantback interval and will therefore make 

no contribution to the dietary intake. Therefore, despite this data deficiency, there are no 

residual uncertainties in the exposure database. 

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose-response assessment, endpoints, cancer 

classification or recommendation to combine routes of exposure. Refer to Table 4.3.1 for a 

summary or toxicological doses and endpoints.

Table 4.3.1. Summary of Toxicological Doses and Endpoints for Imazosulfuron for Use in Dietary, NonOccupational and Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/ 

Safety Factors

RfD, Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

NOAEL= 

400 

mg/kg/day

UFA= 10X

UFH= 10X

FQPA SF = 1X

Acute RfD = 4 

mg/kg/day

aPAD = 4 

mg/kg/day

Acute neurotoxicity screening battery (rat; 

MRID 47305319).

LOAEL = 2000 mg/kg/day based on the 

following clinical signs: abnormal gait, 

decreased activity, piloerection and 

upward curvature of the spine; and 

incidents of irregular breathing, reduced 

righting reflex, tremors, decreased visual 

placement response in males and increased 

response to sound in one female.

Acute Dietary

(Females 13-49 

years of age)

An acute reference dose was not identified for females age 13-49 because there was no prenatal or 

fetal toxicity observed in developmental or reproductive animal studies following a single oral 

dose. 

Chronic 

Dietary (All 

Populations)

NOAEL= 

75 

mg/kg/day

UFA= 10X

UFH= 10X

FQPA SF = 1X

Chronic RfD = 

0.75 

mg/kg/day

cPAD =0.75 

mg/kg/day 

Chronic toxicity (dog; MRID 47305305)

LOAEL = 150 mg/kg/day based on 

moderate thyroid hypertrophy (males at 

mid- and high-dose; mild hypertrophy in 

females at high-dose).
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Imazosulfuron for Use in Dietary, NonOccupational and Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/ 

Safety Factors

RfD, Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental Oral 

Short-Term (1-

30 days) and 

IntermediateTerm (1-6 

months)

NOAEL= 

235 

mg/kg/day 

(MRID 

47305232)

UFA= 10X

UFH= 10X

FQPA SF = 1X

LOC for 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).

Dermal ShortTerm (1-30 

days) and 

IntermediateTerm (1-6 

months)

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 or poorly absorbed through the skin and, therefore, a 

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

Inhalation 

Short- Term 

(1-30 days) and 

IntermediateTerm (1-6 

months)

NOAEL= 

235 

mg/kg/day

(MRID 

47305232; 

inhalation 

toxicity

equivalent 

to oral 

toxicity)

UFA= 10X

UFH= 10X

FQPA SF = 1X

LOC for 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). MOE = margin of exposure. LOC = level of 

concern.
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5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized 

in Table 5.1 and defined in Appendix D. The parent compound is an adequate indicator of 

misuse, and is the only residue included in the tolerance expression. The sulfonamide hydrolysis 

products, UDPM and ISPN are also major residues found in plant and livestock commodities, 

respectively, and are included in the dietary risk assessment. The sulfonamide hydrolysis 

products, IPSN, UDPM, ADPM and SDPM and the demethylation product, HMS were major 

degradates in the environmental fate studies so are included in the drinking water assessment. 

HMS has a structure similar to the parent compound, so is assumed to have equal toxicity. The 

hydrolysis products cannot be excluded from hazard considerations as there is potential for 

exposure. Further information on the metabolism and degradation may be found in the risk 

assessment dated 11/03/10 (S. Healy, D362653).

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

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Primary Crop Imazosulfuron, UDPM Imazosulfuron

Rotational Crop Not Applicable Not Applicable

Livestock

Ruminant Imazosulfuron, IPSN Imazosulfuron

Poultry Imazosulfuron, IPSN Imazosulfuron

Drinking Water Imazosulfuron, HMS, IPSN, 

ADPM, UDPM, SDPM Not Applicable

5.2 Food Residue Profile

The nature of the residue in plants is adequately understood based similar metabolism of 

imazosulfuron in three dissimilar crops (rice grain, pepper and tomato): hydrolysis of the 

sulfonylurea linkage is the major metabolic process. The residue of concern for tolerance 

enforcement for plants is imazosulfuron. The residue of concern for dietary risk assessment for 

plants is the sum of imazosulfuron and the metabolite UDPM, expressed as equivalents of 

imazosulfuron. The qualitative nature of the residues of imazosulfuron in livestock is adequately 

understood based on investigation made on lactating goats and hens. It was demonstrated that 

metabolism of imazosulfuron is similar in ruminants and poultry. HED concluded that the 

residue of concern for tolerance enforcement in livestock is imazosulfuron and the residue of 

concern for dietary risk assessment in livestock is the sum of imazosulfuron and the metabolite 

IPSN, expressed as equivalents of imazosulfuron.

Crop Field Trials

All crop trials on potato reflected a 3x exaggerated-rate application. Residues of imazosulfuron 

were <0.02 ppm on potato harvested 42-48 days following sequential (preemergence followed by 
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postemergence) application of the 75% WDG formulation for a total rate of 0.873-0.919 lb ai/A. 

Maximum residues of imazosulfuron were <0.02 ppm in/on cantaloupe harvested 48-68 days 

following 1-2 broadcast applications of the 75% WDG formulation of imazosulfuron, at 0.3 lb 

ai/A. 

The studies reflected the proposed use patterns for potato and cantaloupe. The number and 

location of field trials are in accordance with OPPTS Guideline 860.1500 for each crop. The 

available data on cantaloupe will support the proposed tolerance of 0.02 ppm for melon crop 

subgroup 9A. The available data on potato support the proposed tolerance of 0.02 ppm for 

tuberous and corm vegetables crop subgroup 1C.

Processing Studies

The submitted potato processing study is adequate. The residues of imazosulfuron following a 

3x application were below the LOQ (<0.02 ppm) in all samples of potato and potato processed 

fractions (potato flakes, chips and wet peels). Imazosulfuron residues will not concentrate in 

potato processed matrices relative to the raw agricultural commodity.

Storage Stability

The submitted storage stability data on potato, potato processed commodities, and cantaloupe are 

adequate. Storage stability data demonstrated that imazosulfuron residues in/on cantaloupe in/on

potato RAC and in potato processed commodities (potato chips, flakes, and wet peels) were 

stable for the storage intervals of samples from the field trials and processing study. 

Meat, Milk, Poultry and Eggs

The ruminant and poultry feeding study requirements were waived previously because of the 

very low anticipated dietary burdens of imazosulfuron in livestock. The situation remains 

unchanged with the addition of potato wastes where residues are <0.02 ppm. 

Confined Rotational Crops

In the confined rotational crop study, imazosulfuron was not identified in any rotational crop 

commodity. HMS and UDPM were identified as major metabolites in rotational sorghum and 

wheat matrices (except grain) at PBIs of 30 – 120 days. In addition, three metabolites were 

identified in rotational sorghum and wheat feed matrices (except grain) that were not identified 

in primary crops, IPSA-isoserine, IPSA-acetylisoserine, and IPSA-caffeoylisoserine. HED does 

not consider the low levels of these IPSA-conjugates at the 365-day PBI to be toxicologically 

significant. Appropriate PBIs were required to insure no quantifiable residues in rotational 

crops.

5.3 Water Residue Profile

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

risk assessment for the Section 3 proposed new use registration of imazosulfuron. Modeled 

application rates represent the maximum application rates on the proposed label for use on the 

melon subgroup 9A and the tuberous subgroup 1C. Tier 1 surface water and groundwater 

modeling was conducted for two ground spray applications with a 45-day interval for the 

tuberous and corm subgroup 1C at a rate of 0.15 lb a.i./A. In addition, Tier 1 surface water 
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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modeling was also conducted for one ground spray application for melon subgroup 9A use at a 

rate of 0.3 lb a.i./A per year (D402305, F. Khan, 16-NOV-2012).

The estimated drinking water concentrations (EDWCs) for Tier 1 models are lower than the 

previously reported EDWC of 278.9 μg/L for acute and chronic exposures for surface water 

based on the rice scenario and 4.8 μg/L for acute and chronic exposures for ground water based 

on the turf scenario (Table 5.3). Therefore, the previously recommended EDWCs should be 

retained for drinking water exposure assessment for human health risk assessment purposes.

Table 5.3 Summary of Estimated Surface Water and Groundwater Concentrations 

for Imazosulfuron.

Scenario Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 278.9 4.8

Chronic (non-cancer) 278.9 4.8

a

From the RICE model. Input parameters for all models are tabulated in DP362654, Faruque Khan, 5/13/2010

b

From the SCI-GROW model.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Unrefined acute and chronic dietary assessments were conducted using field trial data and 

assuming 100% of the crops were treated and that all treated crops contained residues at 

tolerance levels. Default processing factors were assumed for the requested crop uses. The 

highest estimated drinking water concentration (EDWC) for imazosulfuron resulted from the 

Tier I RICE model. This recommended EDWC of 278.9 μg/L used in the acute and chronic 

assessment is based on aerial spray application of 0.3 lbs. a.i./A per year for rice.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The dietary analyses assumed that 100% of the crop was treated (100% CT).

5.4.3 Acute Dietary Risk Assessment

Acute dietary risk analyses were conducted with the DEEM-FCID model to form a conservative 

evaluation of exposure for imazosulfuron. At the 95th percentile of exposure, all acute analyses 

yielded risk estimates well below the 100% of the aPAD threshold level of concern for each 

population subgroup. For food and drinking water, the U.S. Population subgroup acute 

aggregate dietary risk was calculated at <1% of the aPAD with an exposure level of 0.015 

mg/kg/day. For the subgroup with the highest calculated exposure, all infants, acute aggregate

dietary risk occupied 1.2% of the aPAD with an exposure of 0.048 mg/kg/day. An overview 

summarizing the results of the acute dietary assessments with the population subgroup having 

the highest exposure noted in bold is presented in Table 5.4.6.

5.4.4 Chronic Dietary Risk Assessment
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Chronic dietary risk analyses were conducted with the DEEM-FCIDTM model to form a

conservative evaluation of exposure for imazosulfuron. All chronic analyses yielded risk 

estimates well below the 100% of the cPAD threshold level of concern for each population 

subgroup. For food and drinking water, the U.S. Population subgroup chronic aggregate dietary 

risk was calculated at <1.0% of the cPAD with an exposure level of 0.0060 mg/kg/day. For the 

subgroup with the highest calculated exposure, all infants, chronic aggregate dietary risk 

occupied 2.0% of the cPAD with an exposure of 0.020 mg/kg/day. An overview summarizing 

the results of the chronic dietary assessment with the population subgroup having the highest 

exposure noted in bold is presented in Table 5.4.6.

5.4.5 Cancer Dietary Risk Assessment

Imazosulfuron is classified as “Not Likely to be Carcinogenic to Humans”. Therefore, a cancer 

dietary exposure assessment was not conducted.

5.4.6 Summary Table

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

Imazosulfuron

Population 

Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% 

aPAD*

Dietary 

Exposure

(mg/kg/day)

% 

cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. 

Population 0.015361 < 1 0.005957 < 1

N/A N/A

All Infants (<1 year 

old) 0.047750 1.2 0.015210 2.0

Children 1-2 years 

old 0.023786 < 1 0.008712 1.2

Children 3-5 years 

old 0.019404 < 1 0.007367 1.0

Children 6-12 years 

old 0.014765 < 1 0.005292 < 1

Youth 13-19 years 

old 0.012823 < 1 0.004362 < 1

Adults 20-49 years 

old 0.015069 < 1 0.005927 < 1

Adults 50 -99 years 

old 0.013496 < 1 0.005848 < 1

Females 13-49 years 

old 0.015336 < 1 0.005898 < 1

* % PADs are reported to 2 significant figures. The values for the highest population for each 

type of risk assessment are bolded.
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

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

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

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

impacts the human health aggregate risk assessment for imazosulfuron.

6.1 Residential Handler Exposure

Residential handler exposure is expected to be short-term in duration. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners.

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 residential exposure. Residential 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-term risks, daily inhalation exposures 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 140,000 (manually pressurized handwand

application) to 50,000,000 (sprinkler can application). These risk estimates are not of concern to 

HED.

Summaries of the inhalation risk estimates for residential handlers are included in Table 5.1. 

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 residential 

handler scenarios.

Table 6.1. Residential Handler Non-cancer Exposure and Risk Estimates for Imazosulfuron.

Exposure Scenario Level of 

Concern

Inhalation Unit 

Exposure

(mg/lb ai)

Maximum 

Application Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose

(mg/kg/day)3 MOE4

Mixer/Loader/Applicator

Lawn/turf : manually 

pressurized handwand

100 1.1 0.025 lb ai/gal 5 gal 0.0017 140,000

Lawn/turf : hose-end 

sprayer

100 0.022 0.75 lb ai/A 0.5 A 0.00010 2,300,000

Lawn/turf : backpack 

sprayer

100 1.1 0.025 lb ai/gal 5 gal 0.0017 140,000

Lawn/turf : sprinkler 

can

100 0.022 0.000017 lb ai/ft2

1000 ft20.0000047 50,000,000

1 Based on registered label (EPA Reg. No. 59639-155).

 

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

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount 

Handled (A/day or gallons/day) ÷ BW (80 kg).

4 Inhalation MOE = Inhalation NOAEL (235 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

6.2 Post-Application Exposure

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

an environment that has been previously treated with imazosulfuron. The quantitative 

exposure/risk assessment for residential post-application exposures is based on the following 

scenarios: incidental oral exposure from treated turf via hand to mouth activities; incidental oral 

exposure from treated turf via object to mouth activities; and incidental oral exposure from 

treated turf via soil ingestion

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

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

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

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

exposed lifestages.

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

post-application risk assessment. Each assumption, factor and algorithm used to estimate 

residential post-application exposure and dose is detailed in the 2012 Residential SOPs1. 

The short-term MOEs for each scenario are greater than the LOC of 100, and are not of concern

(Table 6.2). 

Table 6.2. Residential Post-application Non-cancer Exposure and Risk Estimates for 

Imazosulfuron.

Lifestage

Post-application 

Exposure Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3

Use Site Route of Exposure

Child Turf

Incidental oral

Hand to mouth 0.75 lb ai/A 0.011 21,000

Incidental oral

Object to mouth 0.75 lb ai/A 0.0038 680,000

Incidental oral

Soil ingestion 0.75 lb ai/A 0.000025 9,300,000

1 Based on registered label (EPA Reg. No. 59639-155).

2 Dose (mg/kg/day) equations:

Hand-to-Mouth Dose = hand residue loading (mg/cm2) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm2) 

× exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1-((1-saliva extraction factor (0.5))^(Number of 

hand-to-mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg).

Object-to-Mouth Dose = object residue loading (μg/cm2) × unit conversion factor (0.001 mg/μg) × object surface area mouthed 

/ event (10 cm2/event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1-((1- saliva extraction factor 

(0.50))^(# Object-to-Mouth Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg).

 
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Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

TTR for liquid application rate of 0.75 lb ai/A x 1% x (1-10%)0x conversion factor (ug/lb) x conversion factor (acre/cm2)= 

0.083 μg/cm2.

3 Incidental Oral MOE = Oral NOAEL (235 mg/kg/day) ÷ Incidental oral Dose (mg/kg/day).

6.3 Combined Exposure

Dermal and inhalation risks were not combined in this assessment, since short- and intermediateterm dermal toxicity endpoints were not identified.

6.4 Residential Bystander Postapplication Inhalation Exposure

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

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

inhalation toxicity (Toxicity Category IV), low vapor pressure (< 6.3x10-4Pa at 25oC), and the 

low proposed use rate (0.3 lb ai/A). 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 

imazosulfuron.

6.5 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 (see the Agency’s Spray Drift website for more information4. The 

Agency has completed its evaluation of the new database submitted by the Spray Drift Task 

Force, a membership of U.S. pesticide registrants, and is developing a policy on how to 

appropriately apply the data and the AgDRIFT computer model to its risk assessments for 

pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in 

place, the Agency may impose further refinements in spray drift management practices to reduce 

off-target drift with specific products with significant risk estimates associated with drift.

It is noted that the 0.75 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure of children. As this rate is equal to or higher than many of 

agricultural application rates, this scenario is protective of any exposure of farm children via 

spray drift from agricultural imazosulfuron applications.

 

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

4 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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7.0 Aggregate Exposure/Risk Characterization

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

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

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

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

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

duration of exposure.

7.1 Acute Aggregate Risk

Refer to Section 5.4.3, which discusses acute dietary exposure (food and drinking water) in 

detail. The dietary route (food and drinking water) alone is relevant for acute exposure and risk 

assessment; and the acute dietary exposure and risk assessment conducted for imazosulfuron is 

screening-level, wherein the assessment assigns tolerance level residue values to all food 

commodities proposed to be treated with imazosulfuron and modeled residue values to all 

drinking water. No aggregate risk concerns were identified.

7.2 Short- and Intermediate-Term Aggregate Risk

Table 7.2. Short- and Intermediate-Term Aggregate Risk Calculations 

Population

Short- or Intermediate-Term Scenario

LOC for 

Aggregate

Risk1

MOE dietary

(food + drinking 

water)2

MOE 

incidental

oral3

MOE

dermal4

MOE 

inhalation5

Aggregate MOE

(food and 

residential)6

Adult Male 100 43,000 N/A N/A 140,000 33,000

Adult Female 100 43,000 N/A N/A 140,000 33,000

Child 100 15,000 21,000 N/A N/A 8,700

1

The LOC includes the standard inter- and intra- species uncertainty factors (UFA and UFH, respectively) totaling 

100.

2 MOE food = NOAEL/chronic dietary exposure: Where short- and intermediate-term NOAEL = 235 mg/kg/day and 

chronic dietary exposure = 0.005957 mg/kg/day (U.S. population), 0.015210 mg/kg/day (All infants < 1 yr).

3 MOE oral = From Table 6.2.

4 MOE dermal = N/A.

5 MOE inhalation = From Table 6.1.

6 Aggregate MOE (food and residential) = 1 [(1MOE food) + (1MOE oral) + (1MOE inhalation)]

7.3 Chronic Aggregate Risk

Refer to Section 5.4.4, which discusses chronic dietary exposure (food and drinking water) in 

detail. The dietary route alone is relevant for long-term/chronic exposure and risk assessment; 

and the chronic dietary exposure and risk assessment conducted for imazosulfuron is health 

protective (the assessment assigns tolerance-level residue values to all food commodities 

proposed to be treated with imazosulfuron and modeled residue values to all drinking water). No 

chronic aggregate risk concerns were identified.
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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7.4 Cancer Aggregate Risk

The cancer classification is “not likely to be carcinogenic to humans” based on the absence of 

significant tumor increases in two adequate rodent carcinogenicity studies and, therefore, there is 

no concern for cancer risk to humans.

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 imazosulfuron and any other substances and imazosulfuron 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 imazosulfuron 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

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 proposed uses. 

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

following scenarios: mixing/loading WDG (dry flowable) formulations to support groundboom 

application; applying sprays with groundboom equipment; and mixing/loading/applying sprays 

with mechanically pressurized handgun equipment.

The following series of assumptions and exposure factors served as the basis for completing the 

occupational handler risk assessments. 

Application Rate

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

Unit Exposures

It is the policy of HED to use the best available data to assess handler exposure. Sources 

of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force 

(ORETF) database, or other registrant-submitted occupational exposure studies. Some of 

these data are proprietary (e.g., AHETF data), and subject to the data protection 

provisions of FIFRA. The standard values recommended for use in predicting handler 

exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table5”, which, 

 

5 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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along with additional information on HED policy on use of surrogate data, including 

descriptions of the various sources, can be found at the Agency website6. 

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 and applying to support groundboom applications to typical 

acreage field crops; 200 acres for mixing/loading and applying to support groundboom 

applications to high-acreage field crops; and1000 gallons for mixing/loading/applying to 

support mechanically pressurized handgun applications to typical acreage field crops.

Exposure Duration

Based on the proposed use, short- and intermediate-term exposures are expected for 

imazosulfuron. Imazosulfuron is registered for use on a number of crops for multiple 

applications; however, the proposed uses restrict applications to once or twice per 

growing year. Additionally, since the same endpoint and PoD were selected for shortand intermediate-term durations, short-term exposure and risk estimates are considered to 

be protective of intermediate-term exposure and risk. 

Personal Protective Equipment

The imazosulfuron product labels direct mixers, loaders, applicators and other handlers to 

wear long sleeved shirt, long pants, shoes plus socks, and chemical resistant gloves. 

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. 

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. The MOEs 

range from 35,000 (mixing/loading to support ground applications to high acreage crops) to 

2,300,000 (applying with groundboom equipment to typical acreage crops). These risk estimates 

are not of concern to HED. Summaries of the inhalation risk estimates for occupational handlers 

are included in Table 9.1. 

9.1 Short- and Intermediate-Term Handler Risk

Table 9.1. 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

 

6 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table 9.1. 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

Mixing/Loading 

Dry Flowables 

for

Groundboom 

Applications

Melons 0.3 80 0.00896 0.0027 87,000

Tuberous and corm 

vegetables 0.3 200 0.00896 0.0067 35,000

Applicator

Applying 

Sprays via

Groundboom 

Equipment

Melons 0.3 80 0.00034 0.00010 2,300,000

Tuberous and corm 

vegetables 0.3 200 0.00034 0.00026 920,000

Mixer/Loader/Applicator

Mechanically 

pressurized 

handgun

Melons

0.015

(lb 

ai/gal)

1000 0.0039 0.00073 320,000

a Application Rates based on proposed uses on label for V-10142 (EPA Reg. No. 59639-166).

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 (80 kg).

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

9.2 Short- and Intermediate-Term/ Post-Application Risk

9.2.1 Dermal Postapplication Risk

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. Therefore, postapplication dermal exposure was not assessed.

9.2.2 Inhalation Postapplication Risk

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

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

inhalation toxicity (Toxicity Category III and IV), low vapor pressure (< 6.3x10-4Pa at 25oC), 

and the low proposed use rate (0.3 lb ai/A). 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 
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

Page 26 of 37

received the SAP’s final report on March 2, 20103. The Agency is in the process of evaluating 

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

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

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

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

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

for imazosulfuron.

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.

10.0 References

Acierto, A., 09/05/2012, DP#D402303, Imazosulfuron. Request for Section 3 Registration for 

New Uses on the Melon Crop Subgroup 9A and the Tuberous and Corm Vegetables Crop 

Subgroup 1C. Summary of Analytical Chemistry and Residue Data.

Healy, S., 11/03/2010, DP#362653, Imazosulfuron: Human Health Risk Assessment for 

Proposed Uses on Rice, Peppers and Tomatoes. 

Khan, F., 11/13/2008, DP#D358472, The Drinking Water Degradates Identification 

Memorandum for Imazosulfuron.

Khan, F., 08/16/2012, DP#D402035, Tier I Drinking Water Assessment for the Section 3 

Proposed Registration of Imazosulfuron on Melon Subgroup 9A and Tuberous and Corm 

Subgroup 1C

Kramer, G.F., 12/5/2008, DP#D359190, Imazosulfuron: Report of the Residues of Concern 

Knowledgebase Subcommittee (ROCKS).

Rury, K., 02/20/13, TXR 0056566, Imazosulfuron: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of January 23, 2013: Recommendations on the requirement of a 

subchronic inhalation study.

Walls, C., 01/14/2013, DP#D403364, Imazosulfuron: Acute and Chronic Aggregate Dietary 

(Food and Drinking Water) Exposure and Risk Assessments for the New Uses on the Melon Crop 

Subgroup 9A and Tuberous and Corm Vegetables Crop Subgroup 1C

Walls, C., 01/18/2013, DP#D403362, Imazosulfuron: Occupational and Residential Exposure 

Assessment for Proposed Use on Melon Crop Subgroup 9A and Tuberous and Corm Vegetables 

Crop Subgroup 1C.
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for Food Use for Imazosulfuron are in Table 1. Use of the new guideline 

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

Table A.1. Toxicology Data Requirements Technical

Required Submitted

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 (non-rodent)........................................

870.3200 21-Day Dermal ..............................................................

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

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

yes

yes

yes

no

no

yes

yes

yes

no

no

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

870.3700b Developmental Toxicity (non-rodent) ...........................

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

yes

yes

yes

yes

yes

yes

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

870.4100b Chronic Toxicity (non-rodent).......................................

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

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

870.4300 Chronic/Oncogenicity (rat)............................................

n/a

yes

n/a

yes

yes

-

yes

-

yes

yes

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

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

yes

yes

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 Develop. Neuro..............................................................

no

no

yes

yes

no

no

no

yes

yes

no

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

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

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

no

no

yes

yes

no

yes
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile - Test Substance 

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral – rat 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 Acute dermal irritation - rabbit 47305230 Non-irritating IV

870.2600 Skin sensitization – guinea pig 47305231 Negative N/A

870.1100 IHOA 47305222 LD50 > 5000 mg/kg IV

870.1100 UDPM 47305223 LD50 = 677 mg/kg III

870.1100 IPSN 47305224 LD50 = 415 mg/kg, 

males; 445 mg/kg, 

females

II

870.1100 M-1 47305225 LD50 > 5000 mg/kg IV

870.1100 ADPM 47305226 LD50 = 836 mg/kg III
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table A.2.3 Subchronic, Chronic and Other Toxicity Profile of Imazosulfuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (rat)

47305232 (1991);

0, 2500, 10000, 45000 

ppm;

M: 0, 234.7, 956.3, 4577.2 

mg/kg/day;

F: 0, 265.7, 1081.4, 

5135.7 mg/kg/day

Acceptable/Guideline

NOAEL = 235/266 mg/kg/day in 

males/females;

LOAEL = 956/1081 in males/females based on 

reduced mean body weights, body weight gains 

and food efficiency.

870.3100 90-Day oral 

toxicity (mouse)

47305233 (1991);

0, 2500, 10000, 45000 

ppm;

M: 0, 456, 1820, 9776

mg/kg/day;

F: 0, 692, 2727, 12695

mg/kg/day

Acceptable/Guideline

NOAEL = 1820/2727 mg/kg/day in 

males/females;

LOAEL = 9776/12695 mg/kg/day in 

males/females based on central lobular 

hepatocyte hypertrophy and increased liver 

weights. 

870.3150 90-Day oral 

toxicity (dog)

See 47305235; 

Justification to Bridge 

Data from a 1-year 

Chronic Study in Dogs

See 47305305

870.3200 21/28-Day dermal 

toxicity (rat)

47305236 (2006); 

0, 100, 300, 1000 

mg/kg/day

Acceptable/Guideline

NOAEL = 1000 mg/kg/day in males and 

females.

870.3700a Prenatal 

developmental 

(rat)

47305238 (1989); 

0, 250, 500, 1000 

mg/kg/day. Since no 

maternal toxicity was 

observed in the original 

treatment groups, an 

additional treatment group 

of 1500 mg/kg/day was 

added to the study.

Acceptable/Guideline

Maternal NOAEL = 1000 mg/kg/day (limit);

LOAEL = 1500 mg/kg/day based on decreased 

body weight gain and food consumption.

Developmental NOAEL = 1500 mg/kg/day; > 

limit dose;

LOAEL > 1500 mg/kg/day

870.3700b Prenatal 

developmental 

(rabbit)

47305301 (1990);

0, 25, 50, 125 mg/kg/day

Acceptable/NonGuideline*

*tested under FIFRA 

Subdivision F guidelines

Maternal NOAEL = 125 mg/kg/day;

LOAEL > 125 mg/kg/day

Developmental NOAEL = 125 mg/kg/day;

LOAEL > 125 mg/kg/day
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table A.2.3 Subchronic, Chronic and Other Toxicity Profile of Imazosulfuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3800 Reproduction and 

fertility effects

(rat)

47305304 (1990);

0, 100, 1,000, 10,000 

ppm;

MF0: 0, 7.7, 77.8, 777.4

mg/kg/day;

FF0: 0, 8.93, 88.4, 868.5

mg/kg/day;

MF1: 0, 9.0, 89.4, 1006.5

mg/kg/day;

FF1: 0, 9.6, 96.9, 1097.0 

mg/kg/day

Acceptable/Guideline

Parental/Systemic NOAEL = (1000 ppm) 

83.6/92.7 mg/kg/day in males/females (average 

of both generations);

LOAEL = (10,000 ppm) 892/982.7 mg/kg/day 

in males/females (average of both generations)

based on mortality, clinical signs, decreased 

body weights, body weight gains, and food 

consumption. 

Reproductive NOAEL = (10,000 ppm) 

892/982.7 mg/kg/day in males/females 

(average of both generations);

LOAEL > 892/982.7 mg/kg/day in 

males/females (not observed).

Offspring NOAEL = (1000 ppm) 83.6/92.7

mg/kg/day in males/females (average of both 

generations);

LOAEL = (10,000 ppm) 892/982.7 mg/kg/day 

in males/females (average of both generations) 

based on decreased pup viability and body 

weights.

870.4100b Chronic toxicity 

(dog)

47305305 (1990); 

0, 75, 150, 300 mg/kg/day

Acceptable/Guideline

NOAEL = 75 mg/kg/day

LOAEL = 150 mg/kg/day based on moderate 

thyroid hypertrophy (males at mid- and highdose; mild hypertrophy in females at highdose).

870.4200b Carcinogenicity

(mouse)

47305307 (1991);

0, 450, 4500, 45000 ppm;

M: 0, 72.7, 741.3, 7848.1 

mg/kg/day;

F: 86.8, 870.0, 10303.5 

mg/kg/day

Acceptable/Guideline

NOAEL = 73/87 mg/kg/day in males/females.

LOAEL = 741/870 mg/kg/day in males/females

based on centrilobular swelling of hepatocytes.

no evidence of carcinogenicity

870.4300 Chronic 

toxicity/Carcinogen

icity

(rat)

47305306 (1991);

0, 200, 2000, 20000 ppm;

M: 0, 10.39, 106.10, 

1123.99 mg/kg/day;

F: 0, 12.94, 132.46, 

1554.35 mg/kg/day.

Acceptable/Guideline

NOAEL = 106/132 mg/kg/day in 

males/females;

LOAEL = 1124/1554 mg/kg/day in 

males/females based on increased mortality, 

decreased body weight, decreased body weight 

gain, clinical ophthalmic observations 

(cataracts and retinal degeneration) and 

hepatotoxicity in females.

no evidence of carcinogenicity

870.5100 Bacterial reverse 

mutation test

47305308 (1988)

Acceptable/Guideline

TH-913 Technical: Test article has no reverse 

mutagenic potential under these experimental 

conditions

870.5100 Bacterial reverse 

mutation test

47305309 (1990)

Acceptable/Guideline

UDPM: Test article has no reverse mutagenic 

potential under these experimental conditions
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table A.2.3 Subchronic, Chronic and Other Toxicity Profile of Imazosulfuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5100 Bacterial reverse 

mutation test

47305310 (1993)

Acceptable/Guideline

IHOA: Test article has no reverse mutagenic 

potential under these experimental conditions

870.5100

870.5500 

Bacterial reverse 

mutation test; 

DNA repair test

47305311 (1989)

Acceptable/Guideline

M-1: Test article has no reverse mutagenic 

potential under these experimental conditions; 

negative with or without S9 metabolic 

activation 

870.5100 Bacterial reverse

mutation test

47305312 (1988)

Acceptable/Guideline

IPSN: Test article has no reverse mutagenic 

potential under these experimental conditions

870.5100 Bacterial reverse 

mutation test

47305313 (1990)

Acceptable/Guideline

ADPM: Test article has no reverse mutagenic 

potential under these experimental conditions

870.5300 In vitro mammalian 

cell gene mutation 

test

47305314 (1999)

Acceptable/Guideline

Test article is not mutagenic in test system

870.5375 In vitro mammalian 

cell chromosome 

aberration test

47305315 (1988)

Acceptable/Guideline

Test article “was considered to induce no 

chromosomal aberration because the test 

substance showed a suspect positive by the 

direct method but the same results were not 

reproduced.” Test article did not induce 

chromosomal aberrations at any concentration 

in presence of S9.

870.5395 Mammalian 

erythrocyte 

micronucleus test

47305316 (2007)

Acceptable/Guideline

Test article has no potential to induce 

micronuclei in mouse bone marrow cells under 

the conditions of this test

870.6200a Acute neurotoxicity 

screening battery

47305319 (2007);

0, 80, 400, 2000 mg/kg

Acceptable/Guideline

NOAEL = 400 mg/kg/day;

LOAEL = 2000 mg/kg/day in males and 

females based on the following clinical signs: 

abnormal gait, decreased activity, piloerection 

and upward curvature of the spine and 

decreased motor activity in males.

870.6200b Subchronic 

neurotoxicity 

screening battery

47305320 (2007);

0, 800, 2500, 8000 ppm;

M: 0, 54.0, 169.2, 571.3 

mg/kg/day;

F: 0, 61.9, 200.8, 655.3 

mg/kg/day

Acceptable/Guideline

Systemic NOAEL = 169/201mg/kg/day in 

males/females;

LOAEL = 571/655 mg/kg/day in males/females 

based on decreased body weight, body weight 

gain and food efficiency.

Neurotoxicity NOAEL = 571/655 mg/kg/day 

in males/ females (HDT)

LOAEL > 571.7 mg/kg/day for males and > 

655.3 mg/kg/day for females
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table A.2.3 Subchronic, Chronic and Other Toxicity Profile of Imazosulfuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.7485 Metabolism and 

pharmacokinetics

(rat)

47305322 (2007)

Acceptable/Guideline

Parent and 5 metabolites were identified and 

quantified. Parent was detected only in feces 

and amounted to 0.9% of the administered dose 

(AD). HMS, the predominant metabolite, was 

found in the urine at 6, 12 and 24 hours 

amounting to 31.1, 18.4 and 6.2 % of the dose, 

respectively, and in lesser amounts, in the feces 

(6.5). The lesser metabolites (< 5% AD), 

IHDU, HDS, IPSN and ACIS were identified in 

urine and feces.

870.7485 Metabolism and 

pharmacokinetics

(rat)

47305323 (2007)

Acceptable/Guideline

The absorption rate was estimated to be 

~100%. Near complete elimination (66.4% 

urine, 34.0% bile, 2.4% feces) within 24 hours 

after administration of radiolabeled compound 

was observed.

870.7800 Immunotoxicity 

(rat)

48691003 (2011)

Acceptable/Guideline

Systemic NOAEL = 222 mg/kg/day 

Systemic LOAEL = 710 mg/kg/day based on 

decreased body weight, body weight gain, and 

relative thymus weights; and increased relative 

spleen and adrenal weights

Immunotoxicity NOAEL = 222 mg/kg/day)

Immunotoxicity LOAEL = 710 mg/kg/day 

based on reduced thymus weights and 

decreased anti-SRBC PFC response
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of Imazosulfuron.

Parameter Value Reference1

Melting point/range 198.0 oC 47305112

pH 4.61 at 25 oC (1% suspension in water) 47305105

Density 1.652 at 20 oC 47305105

Water solubility at 20 oC 429 mg/L at pH 7; 3936 mg/L at pH 9 47305115

Solvent solubility 0.820 mg/L in hexane

174.6 mg/L in n-octanol

597.2 mg/L in toluene

4478.5 mg/L in acetone

144.8 mg/L in methanol

12,744.7 mg/L in dichloromethane

2,220.3 mg/L in ethyl acetate

47305105

Vapor pressure at 25 oC below LOD (<3.5 x 10-6Pa) 47305116

Dissociation constant, pKa at 20 oC 3.94 in methanol/0.01 M citrate buffer at 252 nm

0.30 in methanol/HCl at 268 nm

47305113

Octanol/water partition coefficient, 

Log(POW) at 25 oC

2.43 at n-octanol/pH 4 buffer

-0.07 at n-octanol/pH 7 buffer

-1.56 at n-octanol/pH 9 buffer

47305114

UV/visible absorption spectrum pH Wavelength A ε, x104

acidic 238.5 0.8877 3.55

 201.0 1.1653 4.66

neutral 238.0 0.8293 3.32

 232.0 0.8278 3.31

 200.5 1.1497 4.60

basic 244.0 0.7607 3.04

 231.0 0.8500 3.40

47305111
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Appendix C. 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 to determine their dermal and inhalation exposure. Many 

such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as PHED and the Outdoor Residential Exposure Task Force (ORETF). 

EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, 

and has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no 

regulatory barrier to continued reliance on these studies.
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Appendix D. Metabolism Summary Table

Table D.1: Tabular Summary of Metabolites and Degradates

Common 

Name

Chemical Name/

Structure

Matrix

Imazosulfuron 2-chloro-N-[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]imidazo-

[1,2-α]pyridine-3-sulfonamide

Milk

Muscle (goat)

Kidney (goat)

Liver (goat)

Eggs

Muscle (hen)

Fat (hen)

Liver (hen)

Rat feces

Potato

Rice grain

Rice straw

Tomato

HMS; Odemethylated 

imazosulfuron

2-chloro-N-[[(4-hydroxy-6-methoxy-2-

pyrimidinyl)amino]carbonyl]imidazo-[1,2-

α]pyridine-3-sulfonamide

Milk

Kidney (goat)

Fat (hen)

Rat urine

Rat feces

Potato

Rice grain

Rice straw

Tomato

Sorghum forage (rotational 30 day)

Wheat forage (rotational 120 day)

Sorghum forage (rotational 365 day)

Sorghum stover (rotational 30 day)

Sorghum stover (rotational 365 day)

Sorghum grain (rotational 30 day

Sorghum grain (rotational 365 day)

IPSN 2-chloro-imidazo[1,2-a]pyridine-3-sulfonic 

acid amide

Milk

Muscle (goat)

Kidney (goat)

Liver (goat)

N

N

N

N

N

H

N

H

S

O

O

Cl

O

CH3

O

CH3

O

N

N

N

N

N

H

N

H

S

O

O

Cl

O

CH3

OH

O
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table D.1: Tabular Summary of Metabolites and Degradates

Common 

Name

Chemical Name/

Structure

Matrix

Eggs

Muscle (hen)

Fat (hen)

Liver (hen)

Rat feces

Potato

Rice grain

UDPM (4,6-dimethoxy-pyrimidin-2-yl)-urea Eggs

Potato

Rice grain

Rice straw

Tomato

Sorghum forage (rotational 30 day)

Sorghum forage (rotational 365 day)

Wheat hay (rotational 120 day)

Wheat straw (rotational 120 day)

Sorghum stover (rotational 365 day)

Sorghum grain (rotational 30 day)

Wheat grain (rotational 120 day)

Sorghum grain (rotational 365 day)

ADPM 4,6-dimethoxy-pyrimidin-2-ylamine Potato

Rice grain

Rice straw

Tomato

Sorghum forage (rotational 30 day)

Sorghum forage rotational 365 day)

Sorghum stover (rotational 30 day)

Wheat hay (rotational 120 day)

Wheat straw (rotational 120 day)

Sorghum stover (rotational 365 day)

Sorghum grain (rotational 30 day)

Wheat grain (rotational 120 day)

Sorghum grain (rotational 365 day)

ADNG glucose conjugate of 4,6-dimethoxypyrimidin-2-ylamine Potato

IPSA-isoserine 3-(2-chloro-imidazo[1,2-a]pyridine-3-

sulfonylamino)-2-hydroxy-propionic acid

Sorghum forage (rotational 30 day)

Wheat forage (rotational 120 day)

Sorghum forage (rotational 365 day)

Sorghum stover (rotational 30 day)

Wheat hay (rotational 120 day)

Wheat straw (rotational 120 day)

Sorghum stover (rotational 365 day)

Sorghum grain (rotational 30 day)

N

N

S

O

O

Cl

NH2

N

N

N

H

H2N O

CH3

O

CH3

O

N

N

H2N O

CH3

O

CH3
IMAZOSULFURON Human Health Risk Assessment DP No. D409228

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Table D.1: Tabular Summary of Metabolites and Degradates

Common 

Name

Chemical Name/

Structure

Matrix

Wheat grain (rotational 120 day)

Sorghum grain (rotational 365 day)

IPSAacetylisoserine2-acetoxy-3-(2-chloro-imidazo-

[1,2-a]pyridine-3-sulfonylamino)-propionic 

acid

Sorghum forage (rotational 30 day)

Sorghum forage (rotational 365 day)

Sorghum stover (rotational 30 day)

Sorghum stover (rotational 365 day)

Sorghum grain (rotational 30 day)

Wheat grain (rotational 120 day)

Sorghum grain (rotational 365 day)

IPSAcaffeoylisoserine3-(3,4-dihydroxy-phenyl)-acrylic acid 1-

carboxy-2-(2-chloro-imidazo-[1,2-a]pyridine3-sulfonylamino)-ethyl ester

Sorghum forage (rotational 30 day)

Sorghum forage (rotational 365 day)

Wheat forage (rotational 120 day)

Sorghum stover (rotational 30 day)

Wheat hay (rotational 120 day)

Wheat straw (rotational 120 day)

Sorghum stover (rotational 365 day)

Sorghum grain (rotational 30 day)

Wheat grain (rotational 120 day)

Sorghum grain (rotational 365 day)

SDPM 4,6-Dimethoxypyridine-2-

yl)aminocarbonylsulfamic acid

Water 

(photolysis)

N

N

N

H

S

O

O

Cl

OH

O

OH

N

N

N

H

S

O

O

Cl

O

O

OH

O

CH3

N

N

N

H

S

O

O

Cl

O

O

OH

O

OH

OH

O

S

O

O

N

O

N

N

O

N O