2 Proposed Registration of the Herbicide, Im azosulfuron 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 actio n will establish uses on established turf grass (residential and commercial) as well as the firs t food uses, including pepp ers (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, le ucine, and isoleucine th at 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 us e in pepper, rice, and tomato, and V-10142 (EPA Reg. No. 59639-RLL) is an end-use product being proposed for use in establis hed residential and commercial turf grass. Both V-10142 and V10142 Ag are formulated as water dispersible granules and contain 75.0% of the active ingred ient, imazosulfuron. The proposed maximum application rate for the food uses is 0.3 lb ai pe r acre with a single (groun d 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 as sessed 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 imazosulfur on suggest that this herbicide po ssesses relatively low toxicity. Many of the effects of single or repeated dos ing were observed near or beyond the respective

limit doses.

Imazosulfuron is of low acute toxicity (Toxici ty 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 re peated-dose studies was the liver inall species tested. Mild to moderate thyroid effects were a pparent only in the ch ronic 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 toxici ty/carcinogenicity study. Ocular effects (increased incidence of ey e 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 wei ght and body weight gain compared to control were frequent findings throughout the toxicology database for imazosulfuron.

Clinical signs (decreas ed motor activity, abnormal gait, upw ard curvature of the spine and piloerection) were observed in males at the limit dose of the acute neur otoxicity study; however, these effects can be attributed to generalized t oxicity and were resolved by Day 2 of the study.

No neurotoxic effects were obser ved during the subchronic screening battery or noted as clinical signs in any other repeated-dose study.

No developmental effects were observed at the hi ghest 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. Mortal ity was also observed in the parental generation at this dose. No increased quali tative or quantitative offspring su sceptibility 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. Imazosulf uron was determined to be no n-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 lik ely to be carcinogenic to humans,” based on the absence of significant tumor increases.

B. Toxicological End Points and Doses Us ed 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 select ed for assessment of all populations based on a NOAEL of 400 mg/kg/day in the rat acute neurot oxicity study. The LOAEL of 2000 mg/kg/day was based on decreased motor activity, piloerec tion 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 ther e is a substantial dose spread4 between the NOAEL and LOAEL.

2. Chronic Dietary : For chronic dietary exposure, a ch ronic 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 se nsitive 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 reside ntial 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 th e 2-generation reproductive toxicity study and 956 mg/kg/day in the subchronic toxicity study. Co mbined, both studies are appropriate for the duration of exposure a nd 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 derm al 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; therefor e, no endpoints were selected.

6. Cancer : Imazosulfuron is classified as “not like ly to be carcinogenic to humans,” based on the lack of evidence of carcinogenicity in ac ceptable 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 imazosulfur on is largely complete, lacking only an immunotoxicity study. EPA has ev aluated the available toxicity data for imazosulfuron and determined that an additional database uncertainty factor is not needed to account for potential immunotoxicity. The most sensiti ve endpoint in the database is moderate thyroid hypertrophy. Liver toxicity accompanied by body weight and f ood consumption effects is seen throughout the toxicology database. No treatment-related chan ges indicative of potential immunotoxicity were seen in hematology parameters, organ weights (t hymus, spleen), gross necropsy (enlarged lymph nodes) or histopathology (spleen, thymus, lymph node s) when tested up to the limit dose in mice and rats. Therefore, EPA does not belie ve that conducting a special series 870.78005 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 sc reening battery or noted as clinical signs in any other re peated-dose study. Alt hough untoward clinical signs were observed in the acute neurotoxicity study, th ese effects can be attributed to generalized toxicity and were resolved by Day 2 of the study. Based on thes e considerations, there is no need for a developmental neurotoxicity study or addi tional 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 residua l uncertainties in the exposure databases. Data have been requested to confirm the stability of imazosulf uron 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 gr ain (wheat); however, as explained below, EPA does not expect these studies to have a m easurable 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 su lfonylurea chemicals are known to be stable. Therefore, EPA expects imazosulfuron to be stab le 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 cr op study were stored fo r a relatively long interval (9 months) prior to completion of the an alyses. Analysis of an imidozolyl (Im)-label sample after the 9 month period yielded a meta bolic 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 me tabolites/degradates were considered toxicologically significant.

c. Field accumulation in rotational crops (gra in): 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 resu lts of the rotational crop study may allow a shorter plantback interval. The confined rotational crop study showed that imazosulfuron and metabolites will be negligib le (<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 exposur e 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 “a vailable 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 mechan ism 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 to lerance 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 determ ine which chemicals have a common mechanism of toxicity and to evaluate the cumulative eff ects 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 diet ary risk analyses were conduc ted with the Dietary Exposure Evaluation Model (DEEM-FCID, Version 2.03), wh ich 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 95 th percentile of exposure, all acut e 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 im azosulfuron from food and drinking water will occupy <1% of the aPAD for the general U.S. p opulation. 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 le vel of concern (100% of the cPAD) for infants less than 1 year old, the populat ion subgroup with the highest estimated chronic exposure.

2. Residential Risk :

There is a potential for exposure of homeowne rs applying products containing imazosulfuron on home lawns. There is also a potential for pos t-application exposure of adults and children7 entering turf areas that have been treated with imazosulfuron and fo r bystander exposure of adults and children in areas adjacen t to pesticide applications.

For non-dietary exposures, the Agency uses the te rm Margin of Exposure (MOE) to refer to the risk associated with the exposur e estimate. The MOE is defined as the ratio of the selected toxicological point of depart ure (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 highes t dose that produced no adverse effects in the relevant toxicology study. The greater the MOE, the lower the risk. Fo r imazosulfuron, an MOE of 100 or greater indicates th ere are no risks of concern.

• Residential handler exposure: Residential handlers may receive short-term dermal and inhalation exposure to imazosulfuron when mi xing, loading and applying the pesticide on home lawns. Since a dermal endpoint of con cern was not identified for imazosulfuron, only short-term inhalation exposures of residential handlers were a ssessed. MOEs for short-term inhalation exposure range from 2.6 million (bro adcast applications) to 32 million (spot applications) and are, th erefore, 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 i nhalation exposure of bystanders nearby application sites. Finally, chil dren 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 identif y any dermal endpoints of concern for imazosulfuron; and a quantitative post-ap plication inhalation e xposure assessment was not performed for imazosulfuron due to its low ac ute 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). Th erefore, EPA assessed only short-term postapplication incidental oral e xposure 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 take s 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 imazosulf uron is low for all population subgroups ( ≤ 1.4% of the aPAD) and, ther efore, not of concern.

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

water will utilize <1 % of the cPAD for al l population subgroups. Chronic residential exposure to residues of imazo sulfuron is not expected.

• Short-Term Risk: Short-term aggregate exposure take s into account short-term residential exposure plus chronic exposure from food a nd water (considered to be a background8 exposure level). For adults, EPA aggregated short-term residential handler inhalation exposure with chronic dietary exposure from f ood and water. The resulting MOE of 40,000 is not of concern. For children, EPA aggregat ed short-term incidental oral residential exposure plus chronic dietary e xposure 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 resu lt in intermediate-term residen tial 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 imazosul furon 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 a bove 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 activ ities in previously treated fields. These potential sources include volatilization of the pesticide a nd resuspension of dusts and/or particulates that cont ain the pesticide. However, a quantitative oc cupational postapplication inhalation exposure assessment wa s not performed for imazosulfuron, primarily

because of imazosulfuron’s low acute inhala tion toxicity, low vapor pressure (<3.5 x 10 -6 Pa), low proposed use rate (0.3 lb ai/A), and the so il-directed application method (i.e., it is not applied using equipment, such as air blast sprayers, th at would result in higher post-application inhalation exposures).

III. Environmental Risk

A summary of the environmental fate and ecolo gical 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 Broadlea f 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 di ssipation are aerobic and anaerobic biodegradation and aqueous photolysis. Imazosulfur on is expected to degrade with half-lives

of several weeks in aerobic soil environmen t and anaerobic aquatic environments. Aquatic9 photolysis (half-life of 3.5 days) is expected to hasten degradation of imazosulfuron; however, it is stable to aquatic hydrolysis excep t at low pH.

2. Mobility : Because imazosulfuron is mobile to modera tely mobile in soil, it is expected to move from the application s ite into groundwater and surface water. Additionally, off-site movement of imazosulfuron is expected th rough spray drift from aerial and ground spray; however, imazosulfuron is not vol atile 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 degradat e 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 consider ed in the aquatic exposure assessment.

4. Expected Fate Scenario : Dissipation of imazosulfuron in th e environment is expected to occur predominantly via runoff and leaching; however, imazosulfuron in leachate is not expected to persist under anaerobic soil cond itions. Persistence of total toxic residue [imazosulfuron and degradates (HMS, IPSN, AD PM, 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 occu r after application and / or spray drift to water bodies in close proximity to the treatment area occurs.

To address concerns with the potential leach ing 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 gr ound water advisories that stress the potential of runoff after treatment and descriptions of conditions that may promote leaching to groundwater. Required label language is descri bed more fully under the “Proposed Regulatory Decision” section, below.

B. Ecological Risk

Ecological risk characterization in tegrates the results of the e xposure 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 quo tient method. For this method, risk quotients (RQs) are calculated by dividing exposure es timates 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 indicat e 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 propos ed 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 al so the potential for adve rse effects on birds and10 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 or al and sub-acute dietary basi s. 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 signific ant 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 de finitive 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 repo rted a statistically significant number of cracked eggs (5%) and a significant reducti on in the number of hatchlings/eggs laid (14%) in the 1230 mg a i/kg diet treatment gr oup resulting in a NOAEC of 484 mg ai/kg diet. There was also a statis tically significant reduction in female weight gain (28%) and reduction in sh ell thickness resulting in a NOAE C 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 feedi ng habits (granivore, in sectivore, herbivore)

of different birds as well as the nutritive content of different forages. Based on these NOAEC/LOAEC values, chronic dos e-based levels of concer n (LOCs) are exceeded for birds consuming shortgrass, tallgrass, and broa dleaf plants/small insects for turf grass use only (RQs between 1.2 and 2.7). Chronic dose-base d 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 si te of application followi ng applications at the maximum use rate. RQs would be expected to drop rapidly as the distance from the treated area increases or when lower appl ication rates are used. Furthe r, the RQs assume that birds forage for food exclusively on the treated area an d that they consume a single type of food. For instance, the RQ of 2.7 a ssumes that birds consume only short grass, the food source expected to result in the greatest imazosulfu ron 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 es timated. EPA also notes that the models used

to estimate concentrations of imazosulfur on in the environment are screening models, designed to provide high-end e xposure estimates, further re ducing the like lihood of actual

risk to birds.11 Although the risk of chronic eff ects 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 potentia l exposure to imazosulfuron residues.

2. Risk to Mammals:

Acute Risk: Imazosulfuron does not pos e a potential risk to mammals on an acute oral exposure basis. The acute endpoints for mamm als are non-definitive, since no treatmentrelated mortality effects were s een at the highest concentration tested; therefore, no acute risk quotients (RQs) were calculated.

The acute oral studies showed an increased acu te sensitivity in mammals to the degradates IPSN, ADPM and UDPM as compared to imazosulf uron, with IPSN being the most toxic. In

order to assess acute risk of th ese degradates to mammals, the application rate for turf grass (the highest proposed rate for imazo sulfuron) 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 propos ed 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 ac ute 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 fou nd in a 2-generation laboratory rat reproduction study. Chronic mammalia n dietary-based RQs did not exceed the chronic risk LOC of 1.0 for any of the proposed uses fo r 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, dos e-based chronic risk RQs ranging from 1.1 to

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

Although dose-based RQs exceeded the chronic LO C 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 RQ s 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 applica tion 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 estima te concentrations of imazosulfuron in the environment are screening mode ls, designed to provide high-e nd exposure estimates, further reducing the likelihood of act ual risk to mammals.

Although the risk of chronic effect s 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 eart hworm toxicity studies resulted in LC 50 values of >1000 mg/kg-dw soil for imazosulfur on 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 LD 50 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 fr om all the proposed imazosulfuron uses.

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

Acute Risk: For acute risk to freshwater and mari ne 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 we re 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, imazo sulfuron is not expected to pose risk to freshwater fish from chronic exposure. Ch ronic 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 NOAE C value from chronic exposure study for sheepshead minnow. The low RQ of 0.09 cal culated using the fathead minnow NOAEC value suggests that imazosulfuron does not pos e risk to estuarine/marine fish.

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

Acute Risk: Peak EECs (Estimated Environmental C oncentrations) were compared to acute toxicity endpoints to derive acu te risk quotients. For acute ri sk to freshwater and marine invertebrates, there was no toxicity observed at the highest concentr ation of the technical grade imazosulfuron tested, at 100 mg ai/L nom inal 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. Ch ronic RQs were calculated for sediment-dwelling midge larvae by comparing the highest pore wate r concentration of imazosulfuron that resulted from the rice scenario (279 μ g /L) to the pore water-based NOAEC (11,000 μ g 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

EC 50 and NOAEC values were 63 and 13 mg ai/L , respectively, based on reduced shell deposition. The RQ, calculated us ing the highest peak EEC (279 μ g ai/L for rice) and the13 EC 50 (63,000 μ g ai/L), is <0.01, below the LOC for ch ronic effects to estuarine/marine

invertebrates.

6. Risk to Plants:

Terrestrial Plants: As is expected with herbicides, te rrestrial 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-lis ted 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 terr estrial 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 reduc tions 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 ryeg rass). This is supported by the fact that imazosulfuron is not a grass herbicide. Imazosulfuron exposure may result in non-target plant mortality, especially wh en applied aerially.

Aquatic Plants : LOCs for listed and non-listed aquatic vasc ular 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 tr eatment area, thereby re ducing 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 condi tionally register products contai ning imazosulfuron to be used on turf, tomatoes, peppers (bell and non-bell) an d 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 functi onal immunotoxicity testing of all food and non-food use pesticides on Decem ber 26, 2007. Since this requirement is14 relatively new, this study is not yet available for imazosulfur on. 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 imazosulfur on 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 toleranc es, since an acceptable single-analyte enforcement analytical method is ava ilable to enforce the tolerances.

• 860.1380 Storage Stability . The final report(s) of the st orage 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 fo r tomatoes. Interim data indicate that imazosulfuron is stable in frozen storage; however, the final reports are needed to confirm its stability.

• 860.1850 Confined Accumulati on 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 Ag ency’s risk conclusions for imazosulfuron.

• 860.1900 Field Accumulation in Rotational Crops . The grain (wh eat) rotational crop study is needed to identify maximum levels of residues in grain and livestock feed items (forage, straw) as a function of the plantbac k 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 neg ligible (<0.01 ppm) on forage, hay, straw, stover, and grain at a 365 day plantback interv al. The results of the field rotational crop study may allow a shorter plantback interval.

The environmental fate and effects review conc luded that the database is adequate for a screening level assessmen t 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 expos ure of the degradate IPSN as compared to the parent, imazosulfuron. Although the calc ulated RQs did not exceed the LOCs for mammals, there is still uncertainty regarding th e acute toxicity of ISPN to fish, aquatic invertebrates (water column-dwelling), and a quatic 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) addres sing 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 degradat e, 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 chlo rsulfuron, the first SU herbicide registered in the US (1981), has indicated that chlorsulfuron may have effects on plant seed/fruit production at extremely low c oncentrations. Based on this research, the Agency may require additional plant studies to better characterize the potential for SU herbicides to cause reproducti ve effects in plants. These studies are not guideline requirements for the registration of a new chemical and ar e not being required for imazosulfuron at this time, but may be requi red 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 an d animals, label language will be required that is intended to keep the pesticide on the treatment area, thereby re ducing the potential for exposure of non-target plants and animals. For exampl e, spray drift management language will be required on the occupational/commercial labeling that advises users of applic ator responsibilities and requires specific techniques to reduce the possibi lity of spray drift. In addition, surface and ground water advisories will be required on all labeling, which ma y further reduce residues in drinking water and exposure of non-target organisms.

Label Language Required for all End-use pro ducts 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 ar e classified as havi ng 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 pr oduct is applied and surface water features such as ponds, streams, and springs will reduce the potential loading of imazosulfuron and degradates from runoff wa ter 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 ha ve properties and charac teristics associated with chemicals detected in ground water. Th ese chemicals may leach into ground water if used in areas where soils are permeable, par ticularly 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 Lang uage for Residential Turf Uses: “Do not irrigate within 4 hrs before or af ter application.” “Do not apply if rain is expe cted within 24 hours after application.” “Make broadcast applications with equipmen t at a height no greater th an 2 feet above the ground. Making applications at the lowest he ight 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 wher e possible drift can occu r to unprotected persons or to food, forage or other plantings that might be dama ged or crops thereof rendered unfit for sale, use or consumption.”

Language Required for Labels Th at 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 da ta, 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 us ed 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 equipm ent and weather related factor s 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 appl y the largest droplets that provide sufficient coverage and control. Use nozzle types and nozzle arrangements that will provide maximum coverage and minimize the potential fo r off target movement of spray particles. Droplet size for both ground and ai r applications must be in th e “medium” size category as defined in the August 1999 ASAE S572 publicati on entitled, “Spray Nozzle Classification by Drop Spectra”. Refer to that publication for additional information. Regardless of droplet size, if applications are made im properly or under unfavorable environmental conditions off target movement will occur. (see Wind, Temperatur e and Humidity, and Temperature Inversion sec tions in this label).”17 “Controlling Droplet Size Volume: Use high flow rate nozzles that produce medium dr oplets to apply the highest practical spray volume.”

Pressure: Use the lower spray pressures re commended for the nozzle and do not exceed the manufacturer’s recommended pressure. Higher pressure reduces dropl et 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 th an other orientations. Significant deflection from the horizontal will reduce drop let size and increase drift potential.

Nozzle type: Use a nozzle type that is designed for the intend ed 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 plan ts. Making applications at the lowest possible height reduces exposure of dropl ets 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 th e field, the applicator must compensate for this displacement by adjusting the path of the aircraft upw ind. Swath adjustment distance should increase with increasing drift poten tial (higher wind, smaller drops, etc.).”

“Wind Variable wind speeds with changing directi ons may pose the larges t 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. Howe ver, many factors, in cluding 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 th ey still should remain within the medium droplet size category. Dr oplet evaporation is most severe when conditions are both hot and dry.”18 “Temperature Inversions Do not spray at times when spray particles ma y be entrained into a temperature inversion layer. If inversion conditions are suspected, consult with local weather services before making an application. Applicat ions must not occur during te mperature 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 in creasing temperatures w ith altitude and are common on nights with limited cloud cover and li ght to no wind. They begin to form as the

sun sets and often continue into the morni ng. Their presence can be indicated by ground fog; however, if fog is not pr esent, 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 cl oud (under low wind conditions) indicates an inversion, while smoke that moves upwards and rapidly dissip ates indicates good ve rtical 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 Reducti on Language Required for Aerial Applications to Rice: “Aerial Drift Reduction Advisory : The following aerial drift reduction advisory in formation 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 nozzl es 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 stat es have more stringent regulations, they

must be observed.

4. Do not apply under conditions involving possi ble drift to food, forage or other plantings that might be damaged or the cr ops thereof rendered unfit for sale, use or consumption.

5. When making tank mixture applications follo w 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 particle s from being released into turbulent air. For some use patterns, reducing the effec tive boom length to le ss than 3/4 of the wingspan or rotor length may further re duce drift without re ducing 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 othe r 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 beli eves that the registrati on of sustainable pest control technology for specialty crops and minor uses is beneficial to gr owers, food processors, and the general public and is, th erefore, in the public interest . The public benefits by having high-quality food at reasonable prices. Imazosulfur on will also provide another tool to users for the control of several broadleaf weeds and sedge s in turfgrass and food crops, including difficultto-control yellow nutsedge ( Cyperus esculentus ) and purple nutsedge ( Cyperus rotundu s), as well as pre-emergent and post-em ergent control of ducksalad ( Heteranthera spp .) and Texasweed ( Caperonia palustris ), both of which are signif icant weed problems in rice production.

Imazosulfuron has an excellent human toxicity pr ofile, demonstrating low acute, subchronic and chronic toxicity in the submitted animal st udies. There is no evidence that it causes developmental or reproductive toxicity, neurotoxicity, carcin ogenicity or immunotoxicity; and no evidence of increased susceptibility of infa nts or children to imazosulfuron. Due to imazosulfuron’s lack of dermal toxicity, low acu te 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 anim als, and to birds and mammals on an acute exposure basis. While chronic exposure RQs fo r birds and mammals slightly exceed the LOC,

EPA believes the actual risk to birds and mamma ls 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, cons istent 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 app lication as set forth above will not cause any unreasonable adve rse effect on the environment; and (iii) the registration of imazosulfuron is in the public interest. Accordingly, the Agency proposes to grant these conditional registrations.