2

Proposed Registration of the Herbicide, Imazosulfuron on Peppers (bell and non-bell), 

Rice, Tomatoes and Turf Grass 

Regulatory Rationale 

The Agency is proposing to conditionally grant the first U.S. registrations of the active 

ingredient, imazosulfuron. This registration action will establish uses on established turf grass 

(residential and commercial) as well as the first food uses, including peppers (bell and non-bell), 

tomatoes, and rice. 

I. Chemical Information 

Chemical Name: Imazosulfuron (2-chloro-N-[[4,6-dimethoxy-2-pyrimidinyl)-

amino]carbonyl]imidazo[1,2-a]pyridine-3-sulfonamide) 

EPA PC Code: 118602 

Chemical Abstracts Service (CAS) Number: 122548-33-8 

Mode of Action: Imazosulfuron is a systemic sulfonylurea (SU) herbicide that is absorbed both 

by roots and foliage and is translocated in the xylem and phloem. The mode of action is through 

the inhibition of the enzyme acetolactate synthase (ALS) leading to the blocking of the synthesis 

of the branch-chain amino acids such as valine, leucine, and isoleucine that are essential in the 

formation of new cells. 

Registrant: Valent USA Corporation 

Proposed Products: Imazosulfuron Technical (EPA Reg. No. 59639-RLU), is being proposed 

for use in the formulation of end-use products.V-10142 Ag (EPA Reg. No. 59639-RAA) is an 

end-use product being proposed for use in pepper, rice, and tomato, and V-10142 (EPA Reg. No. 

59639-RLL) is an end-use product being proposed for use in established residential and 

commercial turf grass. Both V-10142 and V10142 Ag are formulated as water dispersible 

granules and contain 75.0% of the active ingredient, imazosulfuron. The proposed maximum 

application rate for the food uses is 0.3 lb ai per acre with a single (ground only) application to 

tomato and pepper and two applications (ground or aerial), 21 days apart, in rice. The proposed 

maximum application rate for turf grass is 0.67 lb ai per acre with a maximum of two 

applications (ground only), 21 days apart, per year. 

II. Human Health Risk 

A summary of the human health effects and risk of imazosulfuron as assessed in the Agency 

document entitled, Imazosulfuron: Human Health Risk Assessment for Proposed Uses on Rice, 

Peppers and Tomatoes, is provided below. 
3

A. Summary of Toxicological Effects 

The toxicity data for imazosulfuron suggest that this herbicide possesses relatively low toxicity. 

Many of the effects of single or repeated dosing were observed near or beyond the respective 

limit doses. 

Imazosulfuron is of low acute toxicity (Toxicity Category III/IV) by the oral, dermal and 

inhalation routes of exposure; it is not a skin or eye irritant or a dermal sensitizer. The primary 

target organ of imazosulfuron in repeated-dose studies 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/day 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) in the 90-day 

feeding toxicity study in rats. Decreased body weight and body weight gain compared to control 

were frequent findings throughout the toxicology database for imazosulfuron. 

Clinical signs (decreased motor activity, abnormal gait, upward curvature of the spine and 

piloerection) were observed in males at the limit dose of the acute neurotoxicity study; however, 

these effects 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 repeated-dose study. 

No developmental effects were observed at the highest dose tested (125 mg/kg/day) in the rabbit 

developmental toxicity study. No developmental or reproductive toxicity was observed in the 

developmental (one-generation) rat study. Decreased pup viability was observed in the rat twogeneration 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 increased qualitative or quantitative offspring susceptibility was apparent in any 

of the submitted studies for imazosulfuron. 

There was no evidence of carcinogenicity in rats and mice up to the limit dose at 24 and 18 

months, respectively. Imazosulfuron was determined to be non-mutagenic in bacteria and 

negative in an in vivo mammalian cytogenetics assay. Overall, there was no evidence that 

imazosulfuron was either mutagenic or clastogenic in either in vivo or in vitro assays. The 

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

significant tumor increases. 

B. Toxicological End Points and Doses Used in the Human Health Risk Assessment 

1. Acute Dietary: For acute dietary exposure, an acute reference dose (aRfD)/acute population 

adjusted dose (aPAD) of 4 mg/kg/day was selected for assessment of all populations based on a 

NOAEL of 400 mg/kg/day in the rat acute neurotoxicity study. The LOAEL of 2000 mg/kg/day 

was based on decreased motor activity, piloerection and upward curvature of the spine observed 

in both sexes and decreased motor activity observed in males only. This is a conservative 

endpoint since effects were seen only at the limit dose and there is a substantial dose spread 
4

between the NOAEL and LOAEL. 

2. Chronic Dietary: For chronic dietary exposure, a chronic reference dose (cRfD)/chronic 

population adjusted dose (cPAD) of 0.75 mg/kg/day was selected for assessment of all 

populations, based on a NOAEL of 75 mg/kg/day with moderate thyroid hypertrophy observed 

in the chronic dietary study in dogs. This study provides the most sensitive endpoints (NOAEL 

and LOAEL); the mouse carcinogenicity study yielded an equivalent NOAEL but with a larger 

dose spread. The selected NOAEL is protective of liver effects. 

3. Short-term (1-30 days) and Intermediate-term (1-6 months) Incidental Oral and 

Inhalation: For short- and intermediate-term residential and occupational exposures involving 

incidental oral and inhalation exposure, the NOAEL of 235 mg/kg/day was selected from the rat 

subchronic toxicity study. This study was co-critical with the 2-generation reproductive toxicity 

study in rats and provided the best estimate of the NOAEL. Similar effects on body weight were 

seen at the LOAEL of 892 mg/kg/day in the 2-generation reproductive toxicity study and 956 

mg/kg/day in the subchronic toxicity study. Combined, both studies are appropriate for the 

duration of exposure and populations exposed. 

4. Short-term (1-30 days) and Intermediate-term (1-6 months) Dermal: No dermal hazard 

was identified in the 21-day dermal toxicity study in rats wherein hepatotoxicity and 

neurotoxicity were assessed. Therefore no dermal endpoint was selected for quantitative risk 

assessment for imazosulfuron. 

5. Long-term (>6 months) Dermal and Inhalation: Neither dermal nor inhalation long-term 

exposure is expected; therefore, no endpoints were selected. 

6. Cancer: Imazosulfuron is classified as “not likely to be carcinogenic to humans,” based on 

the lack of evidence of carcinogenicity in acceptable carcinogenicity studies in the rat and 

mouse. 

C. FQPA Safety Factor 

EPA has determined that reliable data show the safety of infants and children would be 

adequately protected if the FQPA SF were reduced to 1x. That decision is based on the following 

findings: 

1. The toxicology database for imazosulfuron is largely complete, lacking only an 

immunotoxicity study. EPA has evaluated the available toxicity data for imazosulfuron and 

determined that an additional database uncertainty factor is not needed to account for potential 

immunotoxicity. The most sensitive endpoint in the database is moderate thyroid hypertrophy. 

Liver toxicity accompanied by body weight and food consumption effects is seen throughout the 

toxicology database. No treatment-related changes indicative of potential immunotoxicity were 

seen in hematology parameters, organ weights (thymus, spleen), gross necropsy (enlarged lymph 

nodes) or histopathology (spleen, thymus, lymph nodes) when tested up to the limit dose in mice 

and rats. Therefore, EPA does not believe that conducting a special series 870.7800 
5

immunotoxicity study will result in a NOAEL less than 75 mg/kg/day, which is presently used as 

the point of departure for chronic risk assessment. 

2. No neurotoxic effects were observed during the subchronic screening battery or noted as 

clinical signs in any other repeated-dose study. Although untoward clinical signs were observed 

in the acute neurotoxicity study, these effects can be attributed to generalized toxicity and were 

resolved by Day 2 of the study. Based on these considerations, there is no need for a 

developmental neurotoxicity study or additional UFs to account for neurotoxicity. 

3. There is no evidence that imazosulfuron results in increased susceptibility of offspring 

following pre- and postnatal exposure of rats or in utero exposure of rabbits. Neither the rat nor 

rabbit developmental studies identified developmental effects. 

4. There are no significant residual uncertainties in the exposure databases. Data have been 

requested to confirm the stability of imazosulfuron during frozen storage and the metabolic 

profile of pyrimidine-labeled imazosulfuron in rice grain in the confined rotational crop trial. A 

field rotational crop study is also required for grain (wheat); however, as explained below, EPA 

does not expect these studies to have a measurable impact on exposure estimates for 

imazosulfuron. 

a. Storage stability: The final reports of the storage stability studies must be submitted, 

reflecting frozen storage intervals of up to 11.8 months for peppers, up to 34.5 months for 

rice grain, and up to 17.3 months for tomatoes. Interim data suggest that imazosulfuron is 

stable in frozen storage, and similar sulfonylurea chemicals are known to be stable. 

Therefore, EPA expects imazosulfuron to be stable in frozen storage but is requiring the final 

study reports as confirmation. 

 b. Metabolic profile: The HPLC profile for the pyrimidinyl (Py)-label grain storage stability 

analysis must be submitted to confirm that the metabolite profile was stable in Py-label grain. 

Grain samples from the confined rotational crop study were stored for a relatively long 

interval (9 months) prior to completion of the analyses. Analysis of an imidozolyl (Im)-label 

sample after the 9 month period yielded a metabolic profile similar to that of a sample 

analyzed at the start of the period. A similar comparison must be made for the Py-label 

sample of grain. This is of no practical consequence for risk assessment because total 

residue levels on grain were small (<0.01 ppm at a 365-day plantback interval), 

imazosulfuron was not present, and no metabolites/degradates were considered 

toxicologically significant. 

c. Field accumulation in rotational crops (grain): The 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 required 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 dietary 

exposure. 
6

 The dietary food exposure assessments were performed assuming tolerance-level residues 

and 100% crop treated for all commodities. EPA made conservative (protective) 

assumptions in the ground and surface water modeling used to assess exposure to 

imazosulfuron in drinking water. EPA used similarly conservative assumptions to assess 

post-application exposure of children as well as incidental oral exposure of toddlers. These 

assessments will not underestimate the exposure and risks posed by imazosulfuron. 

D. Cumulative Effects 

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, 

or revoke a tolerance, the Agency consider “available information” concerning the cumulative 

effects of a particular pesticide's residues and “other substances that have a common mechanism 

of toxicity.” EPA has not found imazosulfuron to share a common mechanism of toxicity with 

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 assumed that 

imazosulfuron does not have 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 EPA's website at 

http://www.epa.gov/pesticides/cumulative. 

E. Aggregate Risk Assessment 

1. Dietary (Food + Drinking Water) Risk: 

Unrefined acute and chronic dietary risk analyses were conducted with the Dietary Exposure 

Evaluation Model (DEEM-FCID, Version 2.03), which uses food consumption data from the 

USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. 

Acute Dietary Risk: At the 95th percentile of exposure, all acute analyses yielded risk estimates 

well below the threshold level of concern (100% of the aPAD) for each population subgroup. 

The acute aggregate dietary exposure to imazosulfuron from food and drinking water will 

occupy <1% of the aPAD for the general U.S. population. For the subgroup with the highest 

estimated exposure (infants <1 year old), acute aggregate dietary risk will occupy 1.4% of the 

aPAD. 

Chronic Dietary Risk: Estimated chronic dietary exposure to imazosulfuron from food and 

drinking water occupies 2.7% of the threshold level of concern (100% of the cPAD) for infants 

less than 1 year old, the population subgroup with the highest estimated chronic exposure. 

2. Residential Risk: 

There is a potential for exposure of homeowners applying products containing imazosulfuron on 

home lawns. There is also a potential for post-application exposure of adults and children 
7

entering turf areas that have been treated with imazosulfuron and for bystander exposure of 

adults and children in areas adjacent to pesticide applications. 

For non-dietary exposures, the Agency uses the term Margin of Exposure (MOE) to refer to the 

risk associated with the exposure estimate. The MOE is defined as the ratio of the selected 

toxicological point of departure (POD), usually the No Observed Adverse Effects Level 

(NOAEL), to the estimated human exposure. An MOE of 100 means that the estimated level of 

human exposure is 100 times lower than the highest dose that produced no adverse effects in the 

relevant toxicology study. The greater the MOE, the lower the risk. For imazosulfuron, an MOE 

of 100 or greater indicates there are no risks of concern. 

• Residential handler exposure: Residential handlers may receive short-term dermal and 

inhalation exposure to imazosulfuron when mixing, loading and applying the pesticide on 

home lawns. Since a dermal endpoint of concern was not identified for imazosulfuron, only 

short-term inhalation exposures of residential handlers were assessed. MOEs for short-term 

inhalation exposure range from 2.6 million (broadcast applications) to 32 million (spot 

applications) and are, therefore, not of concern. 

• Post-application exposure: Adults and children may receive short-term inhalation and 

dermal exposures from entering turf areas treated with imazosulfuron. Volatilization of 

imazosulfuron may also be a source of short-term post-application inhalation exposure of 

bystanders nearby application sites. Finally, children may receive short-term incidental oral 

exposure (i.e., hand-to-mouth, object-to-mouth and soil ingestion exposure) during postapplication activities on treated turf. EPA did not identify any dermal endpoints of concern 

for imazosulfuron; and a quantitative post-application inhalation exposure assessment was 

not performed for imazosulfuron due to its low acute inhalation toxicity, low vapor pressure 

(<3.5 x 10-6 Pa), low proposed use rate (0.3 lb ai/A), and the soil-directed application method 

(i.e., it is not applied using equipment, such as air blast sprayers, that would result in higher 

post-application inhalation exposures). Therefore, EPA assessed only short-term postapplication incidental oral exposure of children (toddlers). The incidental oral MOE for 

children from combined hand-to-mouth, object-to-mouth and soil ingestion exposures is 

17,000. This MOE is well above 100 and, therefore, not of concern. 

3. Aggregate Risk: 

• Acute Risk: An acute aggregate risk assessment takes into account acute exposure estimates 

from dietary consumption of food and drinking water. As reported above in section E.1., 

estimated acute dietary exposure to imazosulfuron is low for all population subgroups (≤

1.4% of the aPAD) and, therefore, not of concern. 

 

• Chronic Risk: EPA has concluded that chronic exposure to imazosulfuron from food and 

water will utilize <1 % of the cPAD for all population subgroups. Chronic residential 

exposure to residues of imazosulfuron is not expected. 

• Short-Term Risk: Short-term aggregate exposure takes into account short-term residential 

exposure plus chronic exposure from food and water (considered to be a background 
8

exposure level). For adults, EPA aggregated short-term residential handler inhalation 

exposure with chronic dietary exposure from food and water. The resulting MOE of 40,000 

is not of concern. For children, EPA aggregated short-term incidental oral residential 

exposure plus chronic dietary exposure from food and water. The resulting MOE of 7,000 is 

not of concern. 

• Intermediate-Term Risk: Intermediate-term aggregate exposure takes into account 

intermediate-term residential exposure plus chronic exposure from food and water. An 

intermediate-term adverse effect was identified; however, imazosulfuron is not registered for 

any use patterns that would result in intermediate-term residential exposure. Therefore, EPA 

relies on the chronic dietary risk assessment for evaluating intermediate-term risk for 

imazosulfuron. 

F. Occupational Risk Assessment 

1. Handler Exposure and Risk: The proposed uses of imazosulfuron may result in short- and 

intermediate-term occupational inhalation and dermal exposures of mixers, loaders, and 

applicators (both ground and aerial). Since a dermal endpoint of concern was not identified for 

imazosulfuron, only inhalation exposures were quantitatively assessed. 

All handler inhalation MOEs are well above 100 (ranging from 59,000 to 930,000) and are, 

therefore, not of concern. The worst-case MOE of 59,000 is based on handlers mixing and 

loading dry flowable formulations for aerial applications to rice. 

2. Occupational Post-application Exposure and Risk: There are multiple potential sources of 

inhalation exposure of individuals performing post-application activities in previously treated 

fields. These potential sources include volatilization of the pesticide and resuspension of dusts 

and/or particulates that contain the pesticide. However, a quantitative occupational postapplication inhalation exposure assessment was not performed for imazosulfuron, primarily 

because of imazosulfuron’s low acute inhalation toxicity, low vapor pressure (<3.5 x 10-6 Pa), 

low proposed use rate (0.3 lb ai/A), and the soil-directed application method (i.e., it is not 

applied using equipment, such as air blast sprayers, that would result in higher post-application 

inhalation exposures). 

III. Environmental Risk

A summary of the environmental fate and ecological effects and risks of imazosulfuron as 

assessed in the Agency document titled “Ecological Risk Assessment for the First Food Use 

Registration of Imazosulfuron for Selective Sedge and Broadleaf Weed Control in Tomato, 

Pepper, and Rice and Revised Use rates in Turfgrass” is provided below. 

A. Environmental Fate 

1. Degredation: Major routes of imazosulfuron dissipation are aerobic and anaerobic 

biodegradation and aqueous photolysis. Imazosulfuron is expected to degrade with half-lives 

of several weeks in aerobic soil environment and anaerobic aquatic environments. Aquatic 
9

photolysis (half-life of 3.5 days) is expected to hasten degradation of imazosulfuron; 

however, it is stable to aquatic hydrolysis except at low pH. 

2. Mobility: Because imazosulfuron is mobile to moderately mobile in soil, it is expected to 

move from the application site into groundwater and surface water. Additionally, off-site 

movement of imazosulfuron is expected through spray drift from aerial and ground spray; 

however, imazosulfuron is not volatile and, therefore, is not likely to be transported via 

atmospheric processes following application. 

3. Degradates of Concern: The environmental degradates of imazosulfuron that are of possible 

exposure concern for surface water include the parent compound’s major degradates, HMS, 

IPSN, ADPM, UPDM and SPDM. As the degradate HMS retains both major ring structures, 

its toxicity is likely comparable to the parent. IPSN, ADPM, UPDM and SPDM all retain at 

least one of the structural alerts as the parent, and therefore a total toxic residue 

(imazosulfuron + 5 degradates) was considered in the aquatic exposure assessment. 

4. Expected Fate Scenario: Dissipation of imazosulfuron in the environment is expected to 

occur predominantly via runoff and leaching; however, imazosulfuron in leachate is not 

expected to persist under anaerobic soil conditions. Persistence of total toxic residue 

[imazosulfuron and degradates (HMS, IPSN, ADPM, IHOA and SPDM)] in soil is sufficient 

such that vulnerable aquifers may be impacted but exposure will be minimal compared to 

surface water concentrations. Imazosulfuron concentrations in surface waters may be 

relatively high when significant runoff events occur after application and / or spray drift to 

water bodies in close proximity to the treatment area occurs. 

 

To address concerns with the potential leaching and runoff of imazosulfuron and its major 

degradates that may result from the persistence and mobility described above, labels will be 

required to have language including surface and ground water advisories that stress the potential 

of runoff after treatment and descriptions of conditions that may promote leaching to 

groundwater. Required label language is described more fully under the “Proposed Regulatory 

Decision” section, below. 

B. Ecological Risk 

Ecological risk characterization integrates the results of the exposure and ecotoxicity data to 

evaluate the likelihood of adverse ecological effects. The means of integrating the results of 

exposure and ecotoxicity data is called the quotient method. For this method, risk quotients 

(RQs) are calculated by dividing exposure estimates by ecotoxicity values, both acute and 

chronic (RQ = Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). 

The LOCs are criteria used by the Agency to indicate potential risk to non-target organisms. The 

criteria indicate whether a pesticide, when used as directed, has the potential to cause adverse 

effects to non-target organisms. 

A screening-level risk assessment of the proposed uses suggests that imazosulfuron presents 

potential risk to terrestrial and aquatic vascular plants, and thus to the organisms that depend on 

the plants for habitat and forage. There is also the potential for adverse effects on birds and 
10

mammals from chronic exposure to imazosulfuron; however, as discussed below, EPA believes 

the risk of such effects is low. 

1. Risk to Birds:

 Acute Risk: Imazosulfuron and the degradate, ISPN, are considered to be practically nontoxic to birds on an acute oral and sub-acute dietary basis. The acute and sub-acute 

endpoints for avian species are non-definitive, since no treatment-related mortality effects 

were seen at the highest limit dose and dietary concentration tested. The mallard acute oral 

study reported a significant reduction in female body weight gain at the highest treatment 

level; however, based on application rates and the results of these acute toxicity studies, acute 

risk concern levels are not exceeded for birds. 

Chronic Risk: A mallard duck study reported definitive NOAEC/LOAEC (No Adverse 

Effects Concentration/Lowest Adverse Effects Concentration) values of 100/202 mg ai/kg 

diet based on reduced number of eggs laid. A bobwhite quail study reported a statistically 

significant number of cracked eggs (5%) and a significant reduction in the number of 

hatchlings/eggs laid (14%) in the 1230 mg ai/kg diet treatment group resulting in a NOAEC 

of 484 mg ai/kg diet. There was also a statistically significant reduction in female weight 

gain (28%) and reduction in shell thickness resulting in a NOAEC value of 194 mg ai/kg diet 

however these effects were not dose-responsive and there is some uncertainty whether these 

effects were treatment related. 

In order to make the most conservative risk estimation, the mallard duck NOAEC/LOAEC 

value of 100/202 mg ai/kg diet were used to determine chronic dose-based and chronic 

dietary-based RQs. Dose-based RQs differ from dietary-based RQs in that they take into 

consideration the size, metabolic needs and feeding habits (granivore, insectivore, herbivore) 

of different birds as well as the nutritive content of different forages. Based on these 

NOAEC/LOAEC values, chronic dose-based levels of concern (LOCs) are exceeded for 

birds consuming shortgrass, tallgrass, and broadleaf plants/small insects for turf grass use 

only (RQs between 1.2 and 2.7). Chronic dose-based LOCs were not exceeded for any of the 

food uses and chronic dietary-based LOCs were not exceeded for any of the proposed food or 

nonfood uses. 

The chronic “RQs” for birds reflect risk at the site of application following applications at the 

maximum use rate. RQs would be expected to drop rapidly as the distance from the treated 

area increases or when lower application rates are used. Further, the RQs assume that birds 

forage for food exclusively on the treated area and that they consume a single type of food. 

For instance, the RQ of 2.7 assumes that birds consume only short grass, the food source 

expected to result in the greatest imazosulfuron exposure. Since it’s unlikely that birds 

would forage exclusively on the treated area or consume a single type of food, actual risk to 

most birds is likely substantially lower than estimated. EPA also notes that the models used 

to estimate concentrations of imazosulfuron in the environment are screening models, 

designed to provide high-end exposure estimates, further reducing the likelihood of actual 

risk to birds. 
11

Although the risk of chronic effects on birds is low, it cannot be entirely discounted. To 

mitigate potential risk to birds, the proposed labels include language intended to limit spray 

drift, thereby reducing the area of potential exposure to imazosulfuron residues. 

 

 2. Risk to Mammals:

Acute Risk: Imazosulfuron does not pose a potential risk to mammals on an acute oral 

exposure basis. The acute endpoints for mammals are non-definitive, since no treatmentrelated mortality effects were seen at the highest concentration tested; therefore, no acute risk 

quotients (RQs) were calculated. 

The acute oral studies showed an increased acute sensitivity in mammals to the degradates 

IPSN, ADPM and UDPM as compared to imazosulfuron, with IPSN being the most toxic. In 

order to assess acute risk of these degradates to mammals, the application rate for turf grass 

(the highest proposed rate for imazosulfuron) was adjusted to reflect the percent of the 

metabolite that may result from degradation processes on the leaf surface of a grass blade. 

Based on the percent of each degradate detected at the highest proposed application rate, 

acute mammalian LOCs were not exceeded for these degradates. However, there is some 

uncertainty in this analysis as not all degradation processes may have been considered. To 

address this uncertainty and confirm that acute LOCs are not exceeded, additional studies on 

the effects of the most toxic degradate, IPSN, will be required as a condition of registration. 

Chronic Risk: No reproductive effects were found in a 2-generation laboratory rat 

reproduction study. Chronic mammalian dietary-based RQs did not exceed the chronic risk 

LOC of 1.0 for any of the proposed uses for imazosulfuron. Similarly, chronic mammalian 

dose-based risk LOCs were not exceeded for any sized mammals based on imazosulfuron 

uses in tomato, pepper and rice. However, dose-based chronic risk RQs ranging from 1.1 to 

2.3 did exceed the LOC for all sized mammals based on imazosulfuron uses in turf grass. 

Although dose-based RQs exceeded the chronic LOC for mammals in turf grass uses, EPA 

believes the risk of chronic effects is low for several reasons. As noted above in the 

discussion of chronic bird risk, the chronic RQs reflect risk at the site of application 

following applications at the maximum use rate. RQs would be expected to drop rapidly as 

the distance from the treated area increases or when lower application rates are used. 

Further, the RQs assume that mammals forage for food exclusively on the treated area and 

that they consume a single type of food. For most mammals, neither assumption is likely to 

be true. Also, the models used to estimate concentrations of imazosulfuron in the 

environment are screening models, designed to provide high-end exposure estimates, further 

reducing the likelihood of actual risk to mammals. 

Although the risk of chronic effects on mammals is low, it cannot be entirely discounted. To 

mitigate potential risk to mammals, the proposed labels include language intended to limit 

spray drift, thereby reducing the area of potential exposure to imazosulfuron residues. 
12

3. Risk to Pollinators and other Terrestrial Invertebrates:

Imazosulfuron is categorized as practically non-toxic to honey-bees. In addition to the honeybee study, two non-guideline 14-day acute earthworm toxicity studies resulted in LC50

values of >1000 mg/kg-dw soil for imazosulfuron TGAI and >996 mg/kg dw soil for IPSN. 

The effects of IPSN on non-target insects were also documented through 2 non-guideline 

studies, using ground beetles and rove beetles. Both the 14-day study on ground beetle and 

28-day study on rove beetle reported LD50 values of >1000 mg ai/kg dw soil and no effects 

due to IPSN on the beetles. Based on these studies, minimal risk to honey-bees and other 

terrestrial invertebrates is assumed from all the proposed imazosulfuron uses. 

4. Risk to Fish (Freshwater and Estuarine/Marine): 

Acute Risk: For acute risk to freshwater and marine fish, there was no toxicity observed at 

the highest concentration of the technical grade imazosulfuron tested, at 100 mg ai/L nominal 

concentration. Therefore, acute risk quotients were not calculated and there is not a potential 

acute risk to freshwater fish. 

Chronic Risk: As the calculated RQ was less than the chronic risk LOC of 1.0 for all the 

proposed new uses including turfgrass, imazosulfuron is not expected to pose risk to 

freshwater fish from chronic exposure. Chronic toxicity data are not available for 

estuarine/marine fish. As the NOAEC value based on acute exposure studies on fathead 

minnow (for which chronic data are available) and sheepshead minnow were similar, it is 

reasonable to use the fathead minnow NOAEC value from chronic exposure study for 

sheepshead minnow. The low RQ of 0.09 calculated using the fathead minnow NOAEC 

value suggests that imazosulfuron does not pose risk to estuarine/marine fish. 

5. Risk to Aquatic Invertebrates (Freshwater and Estuarine/Marine): 

Acute Risk: Peak EECs (Estimated Environmental Concentrations) were compared to acute 

toxicity endpoints to derive acute risk quotients. For acute risk to freshwater and marine 

invertebrates, there was no toxicity observed at the highest concentration of the technical 

grade imazosulfuron tested, at 100 mg ai/L nominal concentration. Therefore, acute risk 

quotients were not calculated and acute risk to freshwater or marine invertebrates is not 

expected. 

Chronic Risk: The 21-day EECs were compared to chronic toxicity endpoints (NOAEC 

values) to derive chronic risk quotients for invertebrates. Chronic RQs were calculated for 

sediment-dwelling midge larvae by comparing the highest pore water concentration of 

imazosulfuron that resulted from the rice scenario (279 μg /L) to the pore water-based 

NOAEC (11,000 μg ai/L ). The resulting RQ of 0.02 suggests that imazosulfuron is not 

expected to pose risk to freshwater benthic organisms from chronic exposure. There were no 

LOC exceedances for estuarine/marine mollusks based on data for the Eastern Oyster. The 

EC50 and NOAEC values were 63 and 13 mg ai/L, respectively, based on reduced shell 

deposition. The RQ, calculated using the highest peak EEC (279 μg ai/L for rice) and the 
13

EC50 (63,000 μg ai/L), is <0.01, below the LOC for chronic effects to estuarine/marine 

invertebrates. 

6. Risk to Plants:

Terrestrial Plants: As is expected with herbicides, terrestrial plants are sensitive to 

imazosulfuron. For a single ground application on tomato, pepper, and rice at the maximum 

rate, the LOC was exceeded for listed and non-listed non-target terrestrial plants in semiaquatic environments only. For a single aerial application on rice, the LOC was exceeded for 

listed and non-listed non-target terrestrial plants in semi-aquatic environments and listed 

plants in dry upland areas. For a single ground application to turfgrass, the LOC was 

exceeded for listed and non-listed non-target terrestrial plants in dry upland and semi-aquatic 

environments. In addition to the growth effects observed for several plant species, unusually 

high mortality was observed for some plants in the seedling emergence and vegetative vigor 

tests. There were significant reductions in survival at 21 days for soybean at 2 lb ai/A (32%), 

flax at 0.67 lb ai/A (37%), and radish at 0.67 lb ai/A (60%). Minimal effects were observed 

in the Poaceae family (wheat, corn, and ryegrass). This is supported by the fact that 

imazosulfuron is not a grass herbicide. Imazosulfuron exposure may result in non-target plant 

mortality, especially when applied aerially. 

Aquatic Plants: LOCs for listed and non-listed aquatic vascular plants were exceeded for all 

the proposed uses. Non-vascular plant RQs only exceeded concern levels for uses in rice, 

which may be attributed to the extremely conservative nature of the modeling used 

specifically for rice scenarios. An aquatic vascular plant (Lemna gibba) study using the 

degradate, IPSN demonstrated no toxicity to the plant. 

To address and mitigate risks to non-target terrestrial, aquatic and semi-aquatic plants, spray drift 

language intended to keep the pesticide on the treatment area, thereby reducing the potential for 

non-target plant exposure has been added to the proposed labeling of imazosulfuron products. 

IV. Proposed Regulatory Decision 

The Agency is proposing to conditionally register products containing imazosulfuron to be used 

on turf, tomatoes, peppers (bell and non-bell) and rice. As required by FIFRA, the Agency 

published a notice of receipt (NOR) of the registration application in the Federal Register 

(01/27/2010). No comments were received in response to the notice of receipt. 

A. Data Requirements 

The human health risk assessment concluded that the database is largely complete and adequate 

for a dietary, residential, and occupational risk assessment. The following studies are being 

required as a condition of registration: 

• 870.7800 Immunotoxicity . EPA began requiring functional immunotoxicity testing of 

all food and non-food use pesticides on December 26, 2007. Since this requirement is 
14

relatively new, this study is not yet available for imazosulfuron. As explained in section 

II.C., this study is not expected to alter the Agency’s risk conclusions for imazosulfuron. 

• 860.1360 Multiresidue Methods . The following additional information must be 

provided concerning the multiresidue methods testing for imazosulfuron: the petitioner 

must explain why testing for imazosulfuron under Protocol D through the complete 

method without cleanup was not conducted or provide the results of testing without 

cleanup. This information is not used in human health risk assessment. Nor is it critical 

for enforcement of the proposed tolerances, since an acceptable single-analyte 

enforcement analytical method is available to enforce the tolerances. 

• 860.1380 Storage Stability . The final report(s) of the storage stability studies must be 

submitted, reflecting frozen storage intervals of up to 11.8 months for peppers, up to 34.5 

months for rice grain, and up to 17.3 months for tomatoes. Interim data indicate that 

imazosulfuron is stable in frozen storage; however, the final reports are needed to 

confirm its stability. 

• 860.1850 Confined Accumulation in Rotational Crops . The HPLC profile for the 

pyrimidinyl (Py)-label grain storage stability analysis must be submitted to confirm that 

the metabolite profile was stable in Py-label grain. As discussed in section II.C., this 

information is not expected to alter the Agency’s risk conclusions for imazosulfuron.

• 860.1900 Field Accumulation in Rotational Crops . The 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 confined rotational 

crop study showed that residues will be negligible (<0.01 ppm) on forage, hay, straw, 

stover, and grain at a 365 day plantback interval. The results of the field rotational crop 

study may allow a shorter plantback interval. 

The environmental fate and effects review concluded that the database is adequate for a 

screening level assessment of the proposed uses. The following ecological studies are being 

requested as a condition of registration: 

• 850.1075, 850.1300, 850.1300 Acute Toxicity (for a degradate of imazosulfuron). 

Mammals showed increased sensitivity to exposure of the degradate IPSN as compared to 

the parent, imazosulfuron. Although the calculated RQs did not exceed the LOCs for 

mammals, there is still uncertainty regarding the acute toxicity of ISPN to fish, aquatic 

invertebrates (water column-dwelling), and aquatic non-vascular plants exposed to the 

degradate. Studies (Guideline numbers: 850.1075 for fish, 850.1300 for invertebrates, 

and 850.5400 for non-vascular plants) addressing the effects of ISPN on aquatic 

organisms are therefore required as a condition of registration to address this uncertainty 

and confirm that LOCs for aquatic species are not exceeded. 

• 850.2100 Avian Acute Oral Toxicity . The recently revised FIFRA data requirements 

(CFR 40 Part 158) require an avian acute oral toxicity study be conducted using a 

passerine species (Passeriformes). Since the available studies in mallards and quail 

 indicate that imazosulfuron and the degradate, ISPN, are practically non-toxic to birds on 

an acute oral and sub-acute dietary basis, this study is considered to be confirmatory and 

will be requested as a condition of registration. 
15

• Imazosulfuron is a sulfonylurea (SU) herbicide. Research involving chlorsulfuron, the 

first SU herbicide registered in the US (1981), has indicated that chlorsulfuron may have 

effects on plant seed/fruit production at extremely low concentrations. Based on this 

research, the Agency may require additional plant studies to better characterize the 

potential for SU herbicides to cause reproductive effects in plants. These studies are not 

guideline requirements for the registration of a new chemical and are not being required 

for imazosulfuron at this time, but may be required in the future as part of the Agency’s 

effort to address this generic issue for the SU class of herbicides. 

 

B. Labeling Requirements 

In order to mitigate risks to non-target plants and animals, label language will be required that is 

intended to keep the pesticide on the treatment area, thereby reducing the potential for exposure 

of non-target plants and animals. For example, spray drift management language will be 

required on the occupational/commercial labeling that advises users of applicator responsibilities 

and requires specific techniques to reduce the possibility of spray drift. In addition, surface and 

ground water advisories will be required on all labeling, which may further reduce residues in 

drinking water and exposure of non-target organisms. 

Label Language Required for all End-use products to Reduce Residues of Imazosulfuron 

in Drinking Water:

• Surface Water Advisory: 

“Imazosulfuron and its degradates may impact surface water quality through spray and 

runoff of rain water. This is especially true for poorly draining soils and soils with shallow 

ground water. Imazosulfuron and degradates are classified as having high potential for 

reaching surface water via runoff for several months or more after application. A level, 

well maintained vegetative buffer strip between areas to which this product is applied and 

surface water features such as ponds, streams, and springs will reduce the potential loading 

of imazosulfuron and degradates from runoff water and sediment. Runoff of this product 

will be reduced by avoiding applications when rainfall is forecast to occur within 48 

hours.” 

• Ground Water Advisory: 

“Imazosulfuron and several of its degradates have properties and characteristics associated 

with chemicals detected in ground water. These chemicals may leach into ground water if 

used in areas where soils are permeable, particularly where the water table is shallow.” 

Language Required for Labels that include Residential Turf Uses: 

• Buffer Language: 

 “Maintain a 10 ft. vegetative buffer strip between treated areas and natural bodies of water 

 (rivers, streams, lakes, wetlands).” 

• Rate Restriction: “Do not broadcast apply more than 0.66 lb imazosulfuron per acre (.015 

lb ai per 1000 sq. ft.) per year.
16

• Spray Drift/Run-off Management Language for Residential Turf Uses: 

 “Do not irrigate within 4 hrs before or after application.” 

 “Do not apply if rain is expected within 24 hours after application.” 

 “Make broadcast applications with equipment at a height no greater than 2 feet above the 

 ground. Making applications at the lowest height that is safe reduces exposure of droplets 

 to evaporation and wind.” 

 “All ground application equipment must be properly maintained and calibrated using 

 appropriate carriers.” 

 “Do not apply under circumstances where possible drift can occur to unprotected persons 

or to food, forage or other plantings that might be damaged or crops thereof rendered 

unfit for sale, use or consumption.” 

Language Required for Labels That Include Agricultural Uses:

• Use Rate Restriction:“Do not apply more than 0.3 lb imazosulfuron per acre per year.”

• Plant-Back Interval (PBI) Restriction: 

 Pending submission of field rotational crop data, a 12-month plant-back interval must be 

 included for rotation to soybean and cereal grain crops. 

• Labels that include use on rice must include the following restriction: 

 “Do not apply to rice fields if fields are used for the aquaculture of edible fish and/or 

 crustaceans.” 

• Buffer Language: 

 “Do not apply imazosulfuron within 100 feet of emerged non- target crops.” 

 “Maintain a 10 ft. vegetative buffer strip between treated areas and natural bodies of water 

 (rivers, streams, lakes, wetlands).” 

• Spray Drift Management Language: 

“SPRAY DRIFT MANAGEMENT: 

The interaction of many equipment and weather related factors determines the potential for 

spray drift. The applicator and the grower are responsible for considering all factors 

involved in minimizing drift potential.” 

“Importance of Droplet Size

The best drift management strategy is to apply the largest droplets that provide sufficient 

coverage and control. Use nozzle types and nozzle arrangements that will provide 

maximum coverage and minimize the potential for off target movement of spray particles. 

Droplet size for both ground and air applications must be in the “medium” size category as 

defined in the August 1999 ASAE S572 publication entitled, “Spray Nozzle Classification 

by Drop Spectra”. Refer to that publication for additional information. Regardless of 

droplet size, if applications are made improperly or under unfavorable environmental 

conditions off target movement will occur. (see Wind, Temperature and Humidity, and 

Temperature Inversion sections in this label).” 
17

“Controlling Droplet Size

Volume: Use high flow rate nozzles that produce medium droplets to apply the highest 

practical spray volume.” 

Pressure: Use the lower spray pressures recommended for the nozzle and do not exceed the 

manufacturer’s recommended pressure. Higher pressure reduces droplet size and does not 

improve canopy penetration. When higher flow rates are needed, use higher flow rate 

nozzles instead of increasing pressure. 

Number of nozzles: Use the minimum number of nozzles that provide uniform coverage. 

Nozzle orientation: Orienting nozzles so that the spray is released backwards parallel to 

the air-stream will produce larger droplets than other orientations. Significant deflection 

from the horizontal will reduce droplet size and increase drift potential. 

Nozzle type: Use a nozzle type that is designed for the intended application. Do not use air 

inducting or flood type nozzles. 

Ground Boom Application Height: Applications should not be made at a height greater 

than 4 feet above the top of the largest plants. Making applications at the lowest possible 

height reduces exposure of droplets to evaporation and wind.” 

“Swath Adjustment

When applications are made with a cross wind, the swath will be displaced downwind. 

Therefore, on the up and downwind edges of the field, the applicator must compensate for 

this displacement by adjusting the path of the aircraft upwind. Swath adjustment distance 

should increase with increasing drift potential (higher wind, smaller drops, etc.).” 

“Wind

Variable wind speeds with changing directions may pose the largest potential for drift 

damage if crops other than rice are adjacent to the field to be sprayed. Drift potential is 

lowest between wind speeds of 2 to 8 mph. However, many factors, including droplet size 

and equipment type determine drift potential at any given speed. Application must be 

avoided if wind speed is below 2 mph due to variable wind direction and high inversion 

potential. Note: local terrain can influence wind patterns. Every applicator should be 

familiar with local wind patterns and how they affect drift.” 

“Temperature and Humidity

When making applications in low relative humidity, set up equipment to produce larger 

droplets to compensate for evaporation, but they still should remain within the medium 

droplet size category. Droplet evaporation is most severe when conditions are both hot and 

dry.” 
18

“Temperature Inversions

Do not spray at times when spray particles may be entrained into a temperature inversion 

layer. If inversion conditions are suspected, consult with local weather services before 

making an application. Applications must not occur during temperature inversion, because 

drift potential is high. Temperature inversions restrict vertical air mixing, which causes 

small, suspended droplets to remain in a concentrated cloud. This cloud can move in 

unpredictable directions due to the light variable winds common during inversions. 

Temperature inversions are characterized by increasing temperatures with altitude and are 

common on nights with limited cloud cover and light to no wind. They begin to form as the 

sun sets and often continue into the morning. Their presence can be indicated by ground 

fog; however, if fog is not present, inversions can also be identified by the movement of 

smoke from a ground source or an aircraft smoke generator. Smoke that layers and moves 

laterally in a connected cloud (under low wind conditions) indicates an inversion, while 

smoke that moves upwards and rapidly dissipates indicates good vertical air mixing.” 

“Sensitive Areas 

The pesticide must only be applied when the potential for drift to adjacent sensitive areas 

(e.g., residential areas, bodies of water, known habitat for threatened or endangered 

species, non-target crops) is minimal (e.g., when wind is blowing away from the sensitive 

areas).” 

• Additional Spray Drift Reduction Language Required for Aerial Applications to Rice:

 “Aerial Drift Reduction Advisory: 

The following aerial drift reduction advisory information must be followed to avoid offtarget drift movement from aerial applications to agricultural field crops. 

1. Do not spray if wind speed is greater than 8 mph or less than 2 mph. If sensitive crops 

or plants are downwind, extreme caution must be used under all conditions. 

2. The distance between the outermost nozzles on the boom must not exceed 3/4 the 

length of the wingspan or rotor. 

3. Nozzles must always point backward parallel with the air stream and never be pointed 

downwards more than 45 degrees. Where states have more stringent regulations, they 

must be observed. 

4. Do not apply under conditions involving possible drift to food, forage or other 

plantings that might be damaged or the crops thereof rendered unfit for sale, use or 

consumption. 

5. When making tank mixture applications follow the most restrictive label directions, 

including application buffer zones, of each product in the mixture. 

6. Nozzles should be at a minimum of 10 inches below the trailing edge of the wing on a 

fixed wing aircraft to prevent spray particles from being released into turbulent air. 

For some use patterns, reducing the effective boom length to less than 3/4 of the 

wingspan or rotor length may further reduce drift without reducing swath width. 

7. Applications should not be made at a height greater than 10 feet above the top of the 

largest plants unless a greater height is required for aircraft safety. Making 

applications at the lowest height that is safe reduces exposure of droplets to 

evaporation and wind.” 
19

“For aerial applications, do not apply imazosulfuron within a 1/4 mile of emerged cotton or 

non-STS soybeans and do not apply within 100 feet of any other non-target crop.” 

“Aerial application is permitted for rice crop treatments only.” 

C. Public Interest 

The proposed uses of imazosulfuron on tomatoes and peppers (bell & non-bell) are considered 

by the Agency to be minor uses. The Agency believes that the registration of sustainable pest 

control technology for specialty crops and minor uses is beneficial to growers, food processors, 

and the general public and is, therefore, in the public interest. The public benefits by having 

high-quality food at reasonable prices. Imazosulfuron will also provide another tool to users for 

the control of several broadleaf weeds and sedges in turfgrass and food crops, including difficultto-control yellow nutsedge (Cyperus esculentus) and purple nutsedge (Cyperus rotundus), as 

well as pre-emergent and post-emergent control of ducksalad (Heteranthera spp.) and 

Texasweed (Caperonia palustris), both of which are significant weed problems in rice 

production. 

Imazosulfuron has an excellent human toxicity profile, demonstrating low acute, subchronic and 

chronic toxicity in the submitted animal studies. There is no evidence that it causes 

developmental or reproductive toxicity, neurotoxicity, carcinogenicity or immunotoxicity; and 

no evidence of increased susceptibility of infants or children to imazosulfuron. Due to 

imazosulfuron’s lack of dermal toxicity, low acute inhalation toxicity, and low vapor pressure, 

the pesticide poses very low risk to workers or homeowners applying the pesticide or to people 

entering areas that have been treated with imazosulfuron. 

Imazosulfuron poses low risk to aquatic animals, and to birds and mammals on an acute 

exposure basis. While chronic exposure RQs for birds and mammals slightly exceed the LOC, 

EPA believes the actual risk to birds and mammals from chronic exposure to imazosulfuron is 

low. As with all herbicides, imazosulfuron poses risk to non-target plants; however, the RQs for 

non-target plants compare favorably with other herbicides, and the proposed mitigation language 

for end-use product labels should help to mitigate risk to non-target plants. 

Based on these considerations, the Agency believes that the registration of imazosulfuron is in 

the public’s interest. 

D. Proposed Registration Decision 

Based on these considerations, consistent with the requirements of FIFRA section 3(c)(7)(C), 

EPA concludes that (i) it has satisfactory data pertaining to the proposed uses of imazosulfuron 

in turfgrass, tomatoes, peppers (bell and non-bell) and rice; (ii) approving this application as set 

forth above will not cause any unreasonable adverse effect on the environment; and (iii) the 

registration of imazosulfuron is in the public interest. Accordingly, the Agency proposes to grant 

these conditional registrations.