ecological risk assessments in s upport of Registration Review. This document also recommends studies that should be included in a data call-in (DCI) to a ddress uncertaintie s surrounding the environmental fate and potential ecological effects of prosulfuron.1 

# Problem Formulation for the Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments in Support of the Registration Review of Prosulfuron

N-(((4-methoxy-6-methyl-l,3,5-triazin-2-yl)amino)carbonyl)-2-(3,3,3- trifluoropropyl)benzenesulfonamide
CAS No. 94125-34-5 PC Code 129031

P

repared b y : Karen Milians, Ph.D., Chemist Scott Glaberman, Ph.D., Biologist U. S. Environmental Protection Agency Office of Pesticide Programs E nvironmental Fate and Effects Division E nvironmental Risk Branch I V 1200 Pennsylvania Ave., NW M

ail Code 7507P Washington, DC 20460 R eviewed by: Jim Carleton, Ph.D., Senior Scientist Thomas Steeger, Ph.D., Senior Biologist Marietta Echeverria, Branch Chief

April 17, 20124 1. Purpose

The purpose of this problem formulation is to pr ovide an understanding of the environmental fate and ecological effects of the registered us es of prosulfuron (N-(((4-methoxy-6-methyl-l,3,5- triazin-2-yl)amino)carbonyl)-2-(3,3,3 -trifluoropropyl)benzenesulfonamide). Prosulfuron is a selective herbicide registered for weed control on field corn (grown for grain, silage, or seed), popcorn, grain sorghum (milo), wheat, barley, rye, oats, triticale, proso millet, and small grain harvest (Pesticide Registration Division label da ta report as of 10/21/2011). This document will provide a plan for analyzing data relevant to prosulfuron and for conducting environmental fate and ecological risk, endangered species, and drinki ng water assessments for its registered uses. Additionally, this problem formulation is inte nded to identify data gaps, uncertainties, and potential assumptions used to address those uncer tainties relative to characterizing the ecological risk associated with the regi stered uses of prosulfuron.

2. Problem Formulation

2.1. Nature of Regulatory Action

The Food Quality Protection Act of 1996 mandate d the Environmental Protection Agency (EPA) to implement a new program for a ssessing the risks of pesticides, i.e ., Registration Review 1 . All pesticides distributed or sold in the United St ates generally must be registered by EPA. The decision to register a pesticide is based on the co nsideration of scientific data and other factors showing that it will not cause unreasonable risks to human health, workers, or the environment when used as directed on product labeling. Th e Registration Review program is intended to ensure that, as the ability to assess risk e volves and as policies and practices change, all registered pesticides continue to meet the st atutory standard of no unr easonable adverse effects to human health and the environment. Changes in science, public po licy, and pesticide use practices will occur over time. Through th e Registration Review program, the Agency periodically reevaluates pesticides to ensure that as change oc curs, products in the marketplace can be used safely.

As part of the implementation of the new Regist ration Review program purs uant to Section 3(g) of the Federal Insecticide, Fungi cide and Rodenticide Act (FIFRA), the Agency is beginning its evaluation to determine whether prosulfuron continues to meet the FIFRA standard for registration. This problem formulation for the en vironmental fate and ecological risk assessment chapter in support of the regist ration review is intended for th e initial docket opening the public phase of the review process.

2.2. Previous Risk Assessments

The Agency conducted a human health drinking wa ter assessment in 2006 in support of two new uses: small grains and corn (USEPA, 2006). Esti mated drinking water concentrations (EDWCs) in surface water were 1.87, 0.58 and 0.31 μg/L for acute, chronic and lifetime exposure, respectively. The groundwater acute and chronic value was 0.655 μg/L.

1 http://www.epa.gov/oppsrr d1/registration_review5 3. Stressor Source and Distribution

3.1. Mechanism of Action

Prosulfuron belongs to the sulfonyl urea (SU) herbicide family, and it inhibits the activity of the acetolactate synthase (ALS) enzyme in plants which is important for synthesis of branched chain amino acids (leucine, isoleucine , and valine). Prosulfuron is ab sorbed by leaves and roots of susceptible plants. In general, SU herbicides are less toxic to animals than plants (USEPA, 2009).

3.2. Overview of Pesticide Usage

Prosulfuron was registered in 1995, and is a se lective herbicide applied as a post-emergence treatment to control broad leaf weeds in corn, grain sorghum, wint er wheat, spring wheat, barley, rye, oats, triticale, and proso millet. Prosulfu ron is applied after emergence of both crop and weeds for the control of broadleaf weeds on al l registered crops, and postemergence to weeds following small grain harvest. In addition, preemerg ence applications can be used in some areas for broadleaf weed control in sorghum. Prosul furon is applied via ground and aerial spray. The maximum application rate is 0.0356 lbs active ingredient (ai) per acre on corn and sorghum.

Based on market usage data from 2000-2010 (U SEPA, 2011), usage averaged approximately 20,000 lbs ai for 1.6 million acres treated. In additi on, the average application rate over this time period was 0.013 lbs ai/acre. A summary of curr ent registered products of prosulfuron is presented in Table 1

. Table 2 depicts screening levels estimat ed of agricultural uses of prosulfuron (SLUA report, 2011). Corn represen ted the highest percent national use followed by sorghum and wheat for grain.

Table 1. Summary of currently regis tered products of prosulfuron.

Site Description Reg# ai % Product Name Max App Rate (lb

ai/A) Application Method Application Method Timing Disallowed Geo Areas

Barley 100-763 57 Peak ®
Herbicide 0.0178* Aerial Postemergence

Barley 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence

Corn field 100-763 57 Peak ®
Herbicide 0.0356* Aircraft Postemergence

Corn field 100-763 57 Peak ®
Herbicide 0.0356* Ground Postemergence

Corn field 100-774 28.5 Exceed ®
Herbicide 0.0178** Aircraft Postemergence New York

Corn field 100-774 28.5 Exceed ®
Herbicide 0.0178** Ground Postemergence

Corn field 100-911 14.2 Spirit ®
Herbicide 0.00888** Aircraft Postemergence New York

Corn field 100-911 14.2 Spirit ®
Herbicide 0.00888** Ground Postemergence6 Site Description Reg# ai % Product Name Max App Rate (lb

ai/A) Application Method Application Method Timing Disallowed Geo Areas

Corn pop 100-774 28.5 Exceed ®
Herbicide 0.0178** Aircraft Postemergence New York

Corn pop 100-774 28.5 Exceed ®
Herbicide 0.0178** Ground Postemergence

Corn pop 100-911 14.2 Spirit ®
Herbicide 0.00888** Aircraft Postemergence New York

Corn pop 100-911 14.2 Spirit ®
Herbicide 0.00888** Ground Postemergence

Corn (silage) 100-774 28.5 Exceed ®
Herbicide 0.0178** Aircraft Postemergence New York

Corn (silage) 100-774 28.5 Exceed ®
Herbicide 0.0178** Ground Postemergence

Corn (silage) 100-911 14.2 Spirit ®
Herbicide 0.00888** Aircraft Postemergence New York

Corn (silage) 100-911 14.2 Spirit ®
Herbicide 0.00888** Ground Postemergence

Oats 100-763 57 Peak ®
Herbicide 0.0178* Aircraft Postemergence

Oats 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence

Proso Millet 100-763 57 Peak ®
Herbicide 0.0178* Aircraft Postemergence

Proso Millet 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence

Rye 100-763 57 Peak ®
Herbicide 0.0178* Aircraft Postemergence

Rye 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence

Small grains 100-763 57 Peak ®
Herbicide 0.0178* Aircraft Postemergence

Small grains 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence

Sorghum 100-763 57 Peak ®
Herbicide 0.0356* Aircraft Postemergence

Sorghum 100-763 57 Peak ®
Herbicide 0.0356* Aircraft Preemergence

Sorghum 100-763 57 Peak ®
Herbicide 0.0356* Ground Postemergence

Sorghum 100-763 57 Peak ®
Herbicide 0.0356* Ground Preemergence

Triticale 100-763 57 Peak ®
Herbicide 0.0178* Aircraft Postemergence

Triticale 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence

Wheat 100-763 57 Peak ®
Herbicide 0.0178* Aircraft Postemergence7 Site Description Reg# ai % Product Name Max App Rate (lb

ai/A) Application Method Application Method Timing Disallowed Geo Areas

Wheat 100-763 57 Peak ®
Herbicide 0.0178* Ground Postemergence
The formulation for these uses is water dispersable granules/dry flowable. *The label does not specify the number of applications. **Only a single application is allowed.

Table 2. Screening Level Estimates of Agri cultural Uses of Prosulfuron (129031) Sorted Alphabetically
Percent Crop Ttd. Crop Lbs. A.I. Avg. Max. Barley <500 <1 <2.5

Corn 8000 <2.5 5 Sorghum 7,000 5 10

Wheat 4,000 <1 <2.5 *SLUA report, 2011.

3.3. Environmental Fate and Transport

Summary

The environmental fate database for prosulfuron is mostly complete in terms of laboratory and field dissipation data. Th e studies suggest that prosulfuron co uld be persistent and mobile. In addition, hydrolytic degradation is dependent on pH, with neut ral and alkaline media favoring persistence. Photolysis is not an important degradative route for prosulfuron. Long aerobic and anaerobic soil metabolism half- lives were found when compared to aerobic and anaerobic aquatic metabolism. Prosulfuron has the potential to leach and/or be transported by runoff. The major degradates of prosulfuron are those form ed primarily by cleavage of the sulfonylurea bridge, but a desmethyl analog is also a comm on degradate. Degradates formed by opening of the triazine ring have been identified in la boratory studies and in the field. Although, limited environmental fate data are available for degr adates, the data imply that the degradate CGA159902 {2-(3,3,3-trifluoropropyl)-benzenesulfonamide}, as well as CGA-150829 and CGA300406 are likely to impact water sources due to the large per centage of residues found in laboratory studies. Degradate fate data are reviewed later in this section as well as in Appendix A

.
Fate Description

Chemical-physical properties of prosulfuron are summarized in Table 3

. Table 4 summarizes the environmental fate properties of prosulfuro n. Laboratory data in dicate that, like many sulfonylurea (SU) herbicides, prosulfuron is li kely to be persistent and mobile. Chemical (abiotic) hydrolysis and microor ganism-mediated processes are th e major routes of degradation of prosulfuron. Degradation is favored in acid ic media compared to neutral or alkaline conditions. The half-life of abiotic hydrolysis at pH 5 ranged from 3 to 15 days (average from8 two radiolabels: triazine and phenyl); at pH 7 and 9 prosulfu ron was stable during the 30-day duration of the study.

Photodegradation (in water and so il) is not an important degrad ation route for prosulfuron. The electronic absorption spectra (UV-Vis) of the major degradates indica te that they are not prone to direct photolysis.

Both the degradation and dissipa tion kinetics in soil and in water/sediment systems were reported as biphasic and monophasic (or single first order; SFO) processes. The aerobic soil metabolism half-lives of prosulfuron are 121, 211, 138 and 155 days calculated by SFO, primary half-lives ranging from 69 to 152 days and secondary half-lives ranging from 155 to 539 days for the triazine and phenyl label, re spectively. Dissipation half-liv es observed under field conditions ranged from 5.7 to 19.3 days (SFO). In addition, the anaerobic aquatic metabolism data showed that the rate of degradation is increased by the presence of water, as reflected in the shorter halflives (13 days and 20 to 25 days, for the primar y and secondary half-lives, respectively; SFO half-lives are 17.2 and 16.4 days). From the da ta in the anaerobic a quatic metabolism study, there is evidence that most of the degradati on may occur in the aqueous phase. However, anaerobic soil metabolism data in which the soil was not fl ooded showed longer half-lives, which indicate that reactions occurring in the aqueous phase are ma jor contributors to degradation. Information of the degradat es in these studies were capture in Appendix A3.

Prosulfuron has a high potential to leach to groun dwater and to be transported to surface water via runoff and spray drift. This was observed in a field dissipa tion study (MRID 433877-24), where substantial amounts of radioactivity (mos tly parent) was observed in the overflow water (at 15 days) following heavy rainfall events, which suggests potential for runoff. In some field situations ( i.e. acidic soils) significant degradation might occur vi a hydrolysis, but generally prosulfuron is expected to be pe rsistent. Prosulfuron is classified as mobile in soils by the FAO mobility classification criteria , with sorption coefficient (K d ) values ranging from 0.074 to 0.293 L/kg, and organic carbon-norma lized partition coefficient (K oc ) values ranging from 15.2 to 41.3 L/kg oc . However, application rates of the chemical are low, and it may be difficult to detect movement of the chemical from its application site.

The low vapor pressure (<2.6 x10 -8 ) and high water solubility of prosulfuron (43,000 mg/L at pH 7.7) suggest that volatilization is not a major route of dissipa tion. The major degradates of prosulfuron are those formed primarily by cleava ge of the sulfonylurea bridge due to hydrolysis, but the desmethyl analogue is also a common de gradate. Degradates formed by opening of the triazine ring have been identified in laboratory studies and in the field.

Prosulfuron’s octanol/water partition coefficient (K ow ) decreases with increasing pH, and parallels the compound’s increasing water solubility in going from acidic (87 mg/L at pH 5) to more environmentally relevant pHs (43,000 mg/L at pH 7.7). The low octanol water partition coefficient (log K ow range -0.21 - 1.5) suggests the compound is unlikely to bioaccumulate in fish, although no bioconcentration data are available for any organism. The major degradates of prosulfuron are also very so luble in water, and therefor e unlikely to bioaccumulate.

Parent prosulfuron and its major degradates do no t bind strongly to soils, but appear to bind9 irreversibly based on the 24 hours batch equilibrium studies. Prosul furon has the ch aracteristics of a potential leacher and/or of a chemical th at could be transported by dissolved runoff.

Freundlich adsorption coefficients (K f ) of parent prosulfuron is less than 1.0 L/Kg in four different soils ( Table A1 ). The appearance of high amounts of prosulfuron in leachates in soil column leaching studies with un-aged prosul furon indicates a high potential for leaching. However, the Freundlich desorption constant s are much higher than the corresponding adsorption constants suggesting that adsorption/deso rption is not a reversible process. Moreover, soil column leaching with aged prosulfuron s howed a significant decrease in the amount of prosulfuron present in the leachat e and a significant increase in th e amount of prosulfuron in the top 0 to 6 cm of the column. In the field studies, residues of prosulfuron al so tend to stay in the top 0 to 6 inches of soil, wh ile it undergoes degradation.

Prosulfuron has a pKa of 3.76. Therefore, with in creasing pH of the medium, the amount of the anionic form of prosulfuron increases. The incr eased predominance of anionic prosulfuron would reflect in an increase in its leaching and runoff potential.

The major degradates of prosulfuron in the envi ronmental fate laborator y studies are (formationexceeded 10% of applied radioactivity): CGA-159902, CGA-150829, CGA-325030, CGA188838, G-28533, CGA-325025, CGA-325028, and CGA-300406 (See Appendix A3 for chemical structures). The degradate G-28533 appear s to be the most mobile of the degradates. Refer to Table A3 for further details about maximum applied radioactivity found for the degradates. In addition, some of these degradat es are likely to imp act water resources (CGA159902, CGA-150829 and CGA-300406) due to leachi ng and runoff potential. All major and minor transformation products considered as degr adates of concern in the upcoming Registration Review Ecological Risk assessment due to structural similarity to the pare nt and the potential to occur in terrestrial and/or aquatic environments. The proposed approach and rational for including the aforementioned degradates in risk assessment is outlined later in this document (Section 7.1).

Table 3. Summary of physical-chemi cal properties of prosulfuron

Parameter Value and Units Source and/or Comment

PC Code 129031 None

CAS Number 094125-34-5 EPISuite V 4.1

SMILES Code C(F)(F)(F)CCc1ccccc1S(=O)(=O)NC(=O)Nc2nc(C)n c(OC)n2 EPISuite V 4.1

Chemical Name 1-(4-methoxy-6-methyl-triazin-2-yl)-3-(2-(3,3,3- trifluoropropyl)-phenylsulfonyl)-urea MRID 42685247

Empirical Formula C 15 H 16 F 3 N 5 O 4 S EPIsuite V 4.1

Molecular Weight 419.38 EPISuite V 4.1

Melting Point in °C 155 MRID:43387710

Density at 20°C (g/cm 3 ) 1.45 MRID:4338771010 Parameter Value and Units Source and/or Comment

UV/Visible Absorption (nm) pH 5: 201 and 238 pH:7 242 (possible peak at 198) pH9: 242 (possible peak at 196) MRID:43387710

Water Solubility at 25°C in mg/L pH 5: 87 pH 6.8: 4000 pH 7.7: 43000 MRID:43387710 Solubilities of degradates: CGA-150829 (pH 5.7), 300 ppm CGA-159902 (pH 6.7), 270 ppm CGA-300406 (pH 5.8), 400 ppm (unstable) G-28533 (pH 7), > 1000 ppm Vapor Pressure

25°C in torr <2.6x10 -8 MRID:43387710

Henry’s Law constant Not available None

Log Dissociation

Constant (pK a )
25°C 3.76 MRID:43387710

Log K ow

25°C pH 5: 1.5 pH 6.9: -0.21

pH 9: -0.76 MRID:43387710

Table 4. Summary of other environmental fate and transport properties of prosulfuron

Parameter Value(s) and Units Source (Study Classification; (A)=acceptable, (S)=supplemental) Comments

Hydrolysis

half-life (at 25-30°C, in days) pH 5: 3-15 days range pH 7: stable pH 9: stable MRIDs: 42685246 (A),
42685247 (A) Major degradation products at pH 5

were:CGA-159902, CGA 150829, CGA325030, CGA-300406, and G28533.

Aqueous Photolysis

Half-life (days) Stable (<10 to 15% degradation in 30 days, pH 9 only) MRIDs: 46685248 (A), 42685249 (A), 43387710 (A), 43387711(A) These studies (43387710 and 43387711) are additional data on the electronic absorption spectra of several degradates in pH 5, 7 and 9.
Soil Photolysis Half-life (days) Stable (<16 to 21% degradation in 30 days) MRIDs: 43159327 (A), 43159328 (A) None

Aerobic SoilMetabolism Halflife (days) 1 121, 211, 138 and 155 days MRIDs: 42685250 (A), 42685251(A), 43387712(A) and

43387713(A) None

Anaerobic SoilMetabolism Halflife (days) 89 to123 days for Huntington soil; 137 to 138 Kickapoo soil MRIDs: 42685252(A), 42685253(A), 43387714 (A), 43387715 (A) None

Anaerobic Aquatic Metabolism 17.2 and 16.4 MRIDs: 43387717 (A), 43387716 (A) None11 Parameter Value(s) and Units Source (Study Classification; (A)=acceptable, (S)=supplemental) Comments

Aerobic AquaticMetabolism Halflife (days) 59.5 to 68.4 MRIDs: 43387718 (A) and 43387719 (A) None

Soil Partitioning Coefficient (K d , L/kg) Huntington: loamy sand, 0.420 %OC, pH 7.7 and 0.07 L/kg (Kd) Huntington: sandy loam, 1.79 %OC, pH 7.8 0.27 L/kg (Kd) Amour: Silt loam1.58, 1.58 %OC, pH 6.5 and 0.29 L/kg (Kd) Salvisa silty clay loam, 0.610 %OC, pH 6.9 and 0.252 L/kg (Kd) MRIDs: 42685257 (A) Degradates: 43159329

(A), 43159330 (S), 43387720 (A) and

41656209 (A). The mobility of prosulfuron decreased with increasing soil organic matter.

Organic Carbon

Partitioning Coefficient (K oc , L/kg) 23.2 (average of 17.6, 15.2, 18.6 and 41.3)

Soil Column

Leaching In the unaged study prosulfuron was found in the leachate in loamy sand (6.6), sandy loam (pH 6.6),

and loam (pH 6.7) with a radioactivity greater than 88%. MRID: 42685254 (A) The column leaching studies indicate that prosulfuron adsorb irreversible to soils. Mobility appears to decrease with

increasing soil organic matter.

Aged Column

Leaching A 30 days study indicated a significant reduction in the amount of radioactivity of
p rosulfuron recovered in the

leachates (34-61% of the

applied radioactivity). None12 Parameter Value(s) and Units Source (Study Classification; (A)=acceptable, (S)=supplemental) Comments

Terrestrial Field Dissipation Half-life

(days) Radiolabeled studies (Top 3 inches) Kentucky, Silt loam, pH 5.6, 1.9% OM, t 1/2 =11.6 (triazine) to 17.3 (phenyl)

North Carolina, Loamy sand, pH 4.8, <1% OM,

t 1/2 =5.7 (phenyl) to 7.3 (triazine) Cold studies (Top 6 inches) Iowa, Sandy loam, pH 5.4, 2.3% OM Georgia, Loamy sand, pH 7.3, 0.9% OM bare ground Iowa, monophasic 10.2 biphasic: primary 6.2, secondary 31.5 Georgia, monophasic 10.3

biphasic: primary 4.1 secondary 15.0
Corn Iowa, monophasic 19.3 biphasic: primary 7.8 secondary 43.3 Georgia, monophasic 8.8

biphasic: primary 4.2 secondary 13.9 (4 study sites) MRIDs: 43159331 (A), 43159332 (A), 43387721 (A), 43387722 (A), 43387723 (A) Pipe studies with radiolabeled prosulfuron 43387724 (A), 43387725 (A), 43387726 (A) and

43387727 (A) These studies showed much shorter half-lives than laboratory studies with no evidence of parent prosulfuron moving below the 12 inch depth of soil.Degradates: CGA-159902, CGA150829 and CGA-300406.

Steady State Bioconcentration Factor No data Not available None

1 The “half-lives” values presented here represent the be st fit for the disappearance times for each test soil (Huntington sandy loam and Kickapoo sandy loam). For each soil both phenyl- and triazine-ring labeled prosulfuron were tested; the values presented are the average of the results for each of the two soils. There was some evidence of two-compartment adsorption resulting in some modest incr ease in persistence (relative to the first order kinetics model) over the 365-days study period.

Identified transformation products resulting from environmental degradation of prosulfuron; N- [[(4-methoxy-6-methyl-1,3,5-triazin-2-yl )amino]carbonyl]-2-(3,3,3-trifluoropropyl)- benzenesulfonamide are:

• 4-methoxy-6-methyl-1,3,5-triazin-2-amine; CGA-150829 (s-triazine ring cleavage product)-This degradate can produce further de gradation products such as 6-methyl1,3,5-triazine-2,4(1H,3H)-dione (G-28533)

• 4-amino-6-methyl-1,3,5-tr iazin-2(1H)-one; CGA-18883813 • 2-(3,3,3-trifluoropropyl)-benzenesulfonami de; CGA-159902 (phenyl ring cleavage product)

• N-[[(4-hydroxy-6-methyl-1,3,5- triazin-2-yl)amino]carbonyl ]-2-(3,3,3-trifluoropropyl)- benzenesulfonamide; desmethyl prosul furon; desmethyl CGA-152005; CGA-300406

• N-[[(4-amino-6-methyl-1,3,5- triazin-2-yl)-amino]carbonyl ]-2-(3,3,3-trifluoropropyl)- benzenefulfonamide; desmethoxyamino pr osulfuron; desmet hoxyamino CGA-152005; CGA-325025

• N-[[[[[[[[2-(3,3,3-trifluoropropyl)phe nyl]sulfonyl]amino ]carbonyl]amino]- carbonyl]amino]carbonyl]acetamide; Po lyimide Acetate; CGA-325030

• N-[[[[(aminocarbonyl)amino] carbonyl]amino]carbonyl-2-(3,3,3- trifluoropropyl); CGA325028; phenyl ring with sulfonulurea br idge to open triazine chain

• N-[[aminocarbonyl)amino]carbonyl]-2-(3,3,3-trif luoropropyl); CGA- 325026; phenyl ring with sulfonylurea bridge to fragment of triazine

• N-(aminocarbonyl)-2-(3,3,3-tr ifluoropropyl); CGA-325027

• N-[[[4-hydroxymethoxymethyl)-6-methoxy-1,3,5-t riazin-2-yl)amino]carbonyl]-2-(3,3,3- trifluoropropyl); CGA-273437

• N-[[aminocarbonyl)amino]carbonyl]-N-acetyl -2-(3,3,3-trifluoropropyl); NANC-CGA159902 Chemical structures of these de gradation products are shown in Appendix A3, along with details on the maximum amounts observed in laboratory fate studies.

Two major types of degradates can be formed fr om prosulfuron: those in which the sulfonylurea bridge cleaves, producing degradat es containing a single ring and those in which the sulfonylurea bridge remains intact. The latt er type comprises degradates bearing both the phenyl and the triazine ring and degradates in which the triazine ring opens to form aminocarbonyl chains of variable length.

The major bridge-cleavage degradates are CGA-159902 and CGA-15082 9. The latter is a common degradate with triasulf uron and can produce further degradation products such as G28533. The degradates CGA-159902 and CGA-150829 ha ve been identified in all laboratory and field studies (except hydrolys is and photolysis at pH 7 an d 9). The bridge intact CGA300406 have been identified in water and soil, including field studies as well as CGC-325025. It appears that once these degradates form then the sulfonylurea bridge cleaves afterwards.

Opening of the triazine ring was evident in the hydrolysis and photolysis studies at pH 5, in which a degradate consistent with a “pol yimide acetate” group was identified (CGA325030).Other triazine-open degradates with variab le lengths of aminocarbonyl chains have been identified, primarily in soil and sedi ment; CGA-325026 and CGA-325027. The degradate tentatively identified as “NANC-CGA-159902” in th e aquatic metabolism studies has also been detected in the lysimeter.

Monitoring Data

There are only limited monitoring data on prosulfur on, available in a series of publications from the U.S. Geological Survey (Battaglin et al.

, 2000, 2001; Steinheimer et al. , 2000). These publications report that prosulfur on was detected in samples from several Midwestern streams, at14 a maximum concentration of 0.036 μg/L. They al so report an absence of detections in groundwater at 25 monitored sites (minimum det ection limit for the samples was 0.01 μg/L).

The following databases and sources were search ed for monitoring information on prosulfuron on January 15, 2012:

• The United States Environmental Protect ion Agency (USEPA) STORET Database ( http://www.epa.gov/storet/dbtop.html )

• The United States Geological Survey (U SGS) National Water-Quality Assessment (NAWQA) Program Data Warehouse ( http://infotrek.er.usgs.gov /traverse/f?p=NAWQA:HOME:1405517206944567 )

• The USGS National Stream Quality A ccounting Network (NASQAN) program ( http://water.usgs.gov/nasqan /)

• Sampling for Pesticides Residues in Calif ornia Well Water Cumulative Report; EEH03- 08; December 2003 ( http://www.cdpr.ca.gov/docs/emon/pubs/ehapreps/eh0308.pdf )

• California Department of Pesticide Re gulation (DPR) Surface Water Database ( http://www.cdpr.ca.gov/docs/ emon/surfwtr/surfdata.htm )

No monitoring data are available as none of th e databases reported l ooking for prosulfuron.

4. Receptors

Consistent with the process described in th e Overview Document (USEPA, 2004), the risk assessment for prosulfuron will rely on a surrogate species approach. Toxicological data generated from surrogate test species, which are intended to be representa tive of broad groups of organisms, are used to extrapolate potential e ffects on a variety of speci es (receptors) within these groups. Categories of organisms evaluated include: fish, arthropods (insects, crustaceans), mollusks, birds, mammals, aquatic vascular a nd nonvascular plants, a nd terrestrial plants.

Acute and chronic toxicity data from studies submitted by the pe sticide registrant, along with studies available in the open literature, will be us ed to evaluate the potential direct and indirect effects of prosulfuron on aquatic a nd terrestrial receptors. This incl udes toxicity of the technical grade active ingredient, degradat es, and formulated products ( e.g . “six-pack” acute toxicity studies). Open literature studies are iden tified using EPA’s publically available ECOTOX database 2 , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both data so urces may also provide insight into the direct and indirect effects of prosulfuron usage on biotic communities from loss of sensitive species and from changes in community structure or function.

The most sensitive endpoint for each group of organisms is used in risk assessment. Assessment endpoints include direct t oxic effects on the survival, reproduc tion, and growth of terrestrial and aquatic life, as well as indirect effects, such as reduction in pr ey base and/or modification of habitat. A brief summary of the aquatic and terres trial toxicity data available for prosulfuron is provided in Sections 4.1 and 4.2, respectively. A more complete summary of the available data is presented in Appendix B . In addition, a summary of ecologi cal incidents associated with

2 http://cfpub.epa.gov/ecotox/15 prosulfuron and a description of ecosystems potentially at risk ar e provided in Sections 4.3 and 4.4, respectively. Information on degradate toxicity is discussed in the proposed analysis section (Section 7.1).

Toxicity to fish and aquatic invertebrates is categorized using the system shown in Table 5 (US EPA, 2004). Toxicity to terrestrial fauna (birds and mammals) is categorized using the system shown in Table 6 . Toxicity categories for plan ts have not been defined.

Table 5. Categories of Acute T oxicity for Aquatic Animals

LC 50 (m) Toxicity Category

< 0.1 Very highly toxic > 0.1 - 1 Highly toxic > 1 - 10 Moderately toxic > 10 - 100 Slightly toxic

> 100 Practically nontoxic

Table 6. Categories of Acute Toxi city for Terrestrial Animals

LD 50 (mg/kg) LC 50 (ppm) Toxicity Category
<10 <50 Very highly toxic 10-50 50-500 Highly toxic 51-500 501 - 1000 Moderately toxic 501-2000 1001 - 5000 Slightly toxic

>2000 >5000 Practically nontoxic

4.1. Effects to Aquatic Organisms

The most sensitive aquatic toxicity endpoints for each group of organisms ( e.g. , fish, aquatic plants, etc .) from registrant-submitted studies are provided in Table 7 . These endpoints will be used in quantitative risk assessment of prosulfuron. No aquatic toxicity studies were available in ECOTOX as of January 18, 2012 besides those su bmitted by the registrant. A more detailed summary of all aquatic toxici ty studies can be found in Appendix B

.
Prosulfuron is practically non-toxic to aquati c animals based on acute limit tests with the technical grade active ingredient (TGAI). All acute toxicity endpoint values ( i.e., LC 50 /EC 50 ) were estimated to be greater than the limit c oncentration since less than 50% of prosulfurontreated animals died in each test . For chronic toxicity tests, no statistically significant effects were observed for growth, survival, or reproducti on endpoints at any treatment level in either of the aquatic animals tested, i.e ., fathead minnows ( Pimephales promelas ) and daphnids ( Daphnia

magna ). Therefore, the NOAEC for chronic tests are equal to the highest c oncentration tested.

The most sensitive aquatic plant toxicity values are also presented in Table 7 . In several studies with aquatic nonvascular plants, less than 50% inhibition in cell growth occurred at the limit concentration or highest concen tration tested, resulting in non-d efinitive (“greater than”) EC 5016 values. Conversely, definitive toxicity values for the nonvascular freshwater green algae ( Pseudokirchnerie lla subcapitata ) and the vascular freshwater duckweed ( Lemna gibba ) are several orders of magnitude lower (more toxic) compared to aquatic animals.

Table 7. Most Sensitive Aquatic Toxicity Endpoints for Prosulfuron

Species Measured Effect Duration Endpoint Toxicity Value μg ai/L Test Substance % ai MRID (Study Classification)
Freshwater Fish Lepomis macrochirus (Bluegill sunifsh) Mortality 96 hours LC 50 >155,000* † (Practically non-toxic) 99.1% 426852-09 (Acceptable)

Pimephales promelas (Fathead Minnow) Growth, Survival, Hatchability 37 days NOAEC 149,000 99.1% 429497-07 (Acceptable)

Freshwater Crustaceans

Daphnia magna

(Water flea) Immobility 48 hours EC 50 >120,000* † (Practically non-toxic) 99.1 426852-11 (Acceptable)

Growth, Survival, Reproduction 21 days NOAEC 148,000 99.1 429497-08 (Acceptable)

Estuarine/Marine Fish Cyprinodon variegatus (Sheepshead

minnow) Mortality 96 hours LC 50 >155,000* † (Practically non-toxic) 99.1% 429497-06 (Acceptable)

Estuarine/Marine Crustaceans
Americamysis bahia (Mysid shrimp) Mortality 96 hours LC 50 >150,000* † (Practically non-toxic) 99.1% 432126-01 (Supplemental)

Estuarine/Marine Mollusks
Crassostrea

virginica (Eastern oyster) Shell deposition 96 hours EC 50 >125,000* † (Practically non-toxic) 99.1% 432126-02 (Acceptable)
Aquatic Plants Lemna gibba (duckweed) Frond number 14 days EC 50 1.22 98.7% 429497-13 (Acceptable) NOAEC 0.83 Pseudokirchneriella subcapitata (green algae) Tier II Study Cell density 5 days EC 50 10.6

98.7% 429497-14 (Acceptable) NOAEC 2.78

* Non-definitive study endpoint; cannot be used for risk estimation. † Single concentration limit test.

4.2. Effects to Terres trial Organisms

The most sensitive toxicity endpoint values associ ated with prosulfuron exposure to terrestrial organisms are shown in Table 8 . These endpoints will be used in quantitative risk assessment of prosulfuron. More detailed descripti ons of these studies are provided in Appendix B . No toxicity17 studies with terrestrial organisms were avai lable in ECOTOX as of January 18, 2012 besides those submitted by the registrant.

In general, available ecotoxicity data indicate that prosulfuron e xhibits low toxicity to mammals, birds, and honeybees. Prosulfuron is characterize d as being slightly toxic to birds on an acute oral exposure basis, and is prac tically non-toxic to mammals on an acute oral exposure basis and to birds on a subacute dietary exposure basis. Prosulfuron is also practically non-toxic to young adult honey bees ( Apis mellifera ) on an acute contact exposure basi s. A chronic study in mallard ducks revealed decreased hatch success in bird s treated with prosulfuron as compared to controls. Mammal chronic feeding and reproductive toxicity studi es resulted in significant decreases in body weight or body weight gain in parental rats and their offspring.

Prosulfuron is highly toxic to terres trial plants, which is expected gi ven its use as an herbicide. It should be noted that all plant st udies were carried out with pros ulfuron technical. Therefore, effects due to other ingredients used in form ulations are unknown. Terre strial plant toxicity endpoints from studies with the TGAI will not be used in quantitative risk assessment, but may be used for risk characterization. Appendix B contains descriptions of terrestrial plant toxicity studies and endpoints.

Table 8. Most Sensitive Terrestrial T oxicity Endpoints for Prosulfuron

Species Measured effect Endpoint Test Duration Toxicity Value (Acute Toxicity Category) Test Substance % ai MRID (Study Classification) Birds

Anas platyrhynchos (mallard duck) Mortality LD 50 14 days 1094 mg ai/kg-bw (Slightly toxic) 99.2% 426852-05 (Acceptable)

Mortality LC 50 8 days >5000 mg ai/kg-diet*(Practically nontoxic) 99.1% 426852-07 (Acceptable)

Hatching success NOAEC 25 weeks 28 mg ai/kg-diet 99.2% 429497-02 (Acceptable) Mammals

Rattus norvegicus (laboratory rat) Mortality LD 50 14-days 546 mg/kg-bw (females) 99.1% 426852-15 (Acceptable: Reviewed by HED) Body weight, body weight gain (subchronic feeding study) NOAEL 3 months 50 mg/kg-diet (males) (3.1 mg/kg/day) 96% 426852-32 (Acceptable: Reviewed by HED) Terrestrial Arthropods Apis mellifera

(Honeybee) Mortality LD 50 48 hours >100 μg ai/bee 99.1% 426852-12 (Acceptable) * Non-definitive study endpoint; cannot be used for risk estimation.

4.3. Incident Database Review

A search of the EIIS (Environmental Incident Information System) database for ecological incidents (run on January 25, 2012) identified 78 incidents that may involve exposures to prosulfuron. Incidents included in EIIS are de fined by a certainty index associated with the18 likelihood that the pesticide application descri bed resulted in the obs erved incident. The certainty index defines incidents as unrelated, unlikely, possible, probabl e and highly probable. One note of uncertainty associated with this data base is the nature of reporting of incidents. Many more incidents may have occurred due to prosulfuron exposures but may not have been reported due to various factors, such as a lack of reporting, or a lack of witnessing of effects.

All 78 incidents identified by EIIS report plant dama ge. Sixty-five of these incidents were listed as a potential result of direct trea tment of prosulfuron to specific crops or agricultural areas. All except one of the 78 incidents are classified as “probable” in terms of identification of prosulfuron as the causative agent. In 27 cases, incidents are known to have occurred after a registered use of the pesticide, while in six other cases, product s containing prosulfuron were misused or accidentally misapplied.

A search of OPP’s aggregate inci dent report database revealed a total of 37 minor plant incidents between 1998 and 2009 that were attributed to prosulfuron ( Appendix C ).

The Avian Monitoring Information System (AIMS) 3 , which is maintained by the American Bird Conservancy, was also searched on January 25, 2012, and revealed no incidents to birds associated with prosulfuron.

During the risk assessment associated with Regi stration Review of prosulfuron, these databases will be checked again and any additional incidents will be evaluated to determine if they represent current use patterns of prosulfuron. Examples of additional considerations are mitigation ( e.g ., reduced application rates), product can cellations, and changes in use patterns that have occurred since the date of the reported incident(s). It should be noted that incident reports for non-target organisms typically provide information only on mortality events and plant damage. Sublethal effects in organisms such as abnormal behavior, reduced growth and/or impaired reproduction are rarely reported, except fo r phytotoxic effects in terrestrial plants.

4.4. Ecosystems Potentially At Risk

The ecosystems at risk are often extensive in scop e, and as a result it may not be possible to identify specific ecosystems during the development of a baseline risk assessment. However, in general terms, terrestrial ecosystems potentially at risk could include the treated field and areas immediately adjacent to the treated field that may receive drift or runoff. Areas adjacent to the treated field could include cultiv ated fields, fencerows and hedgero ws, meadows, fallow fields or grasslands, woodlands, riparian habita ts and other uncultivated areas.

Aquatic ecosystems potentially at risk include wa ter bodies adjacent to, or downstream from, the treated field and might include impounded bodies such as ponds, lake s and reservoirs, or flowing waterways such as streams or rivers. For uses in coastal areas, aquatic habitat also includes marine ecosystems, including estuaries.

5. Assessment Endpoints

3 http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/login.cfm19 Assessment endpoints are defined as "explicit expressions of the actual environmen tal value that is to be protected." Selection of the asse ssment endpoints is based on valued entities ( e.g ., fish, birds), the ecosystems potentially at risk ( e.g ., water bodies, riparian vegetation, and upland habitats), the migration pa thways of prosulfuron ( e.g ., runoff, drift, etc .), and the routes by which ecological receptors are exposed to prosulfuron ( e.g ., direct contact, etc .). Assessment endpoints for prosulfuron include direct adverse effects on the survival, reproduction, and growth of the receptors, as well as indirect effects, such as reduction of the prey base or modification of habitat. Each assessment endpoint requires one or more "measures of ecological effect," defined as changes in the attributes of an assessment endpoint or changes in a surrogate entity or attribute in response to exposure to a pesticide. Specifi c measures of ecological effect are generally evaluated based on acute and chronic toxicity information from registrant-submitted guideline tests that are performed on a limited number of organisms. Additional ecological effects data from the open literature will also be considered.

6. Conceptual Model

For a pesticide to pose an ecological risk, it mu st reach ecological receptors in biologically significant concentrations. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecological recepto r. For an ecological pathway to be complete, it must have a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, an d a feasible route of exposure.

The conceptual model for prosulfuron provides a wr itten description and vi sual representation of the predicted relationships between prosulfuron and degradates, poten tial routes of exposure, and the predicted effects for the assessment endpoint . A conceptual model consists of two major components: risk hypothesis and a conceptual diagram (USEPA, 1998).

6.1. Risk Hypothesis

A risk hypothesis describes the predicted re lationship among the stre ssor, exposure, and assessment endpoint response along with the rationa le for their selection. For prosulfuron, the following ecological risk hypothesi s is being employed for this national-level ecological risk
assessment:

Given the uses of prosulfuron and its environmen tal fate properties, th ere is a likelihood of exposure to non-target terrestrial and/or aquatic organisms. When used in accordance with the label, prosulfuron and its degradates may result in adverse effects upon the survival, growth, and reproduction of non-target terrestrial and/or aquatic org anisms. These non-target organisms may include Federally-listed threatened and endangered species.

Prosulfuron is both persistent and mobile in soil and may pose a risk to te rrestrial plants near the site of application. Moreover, prosulfuron is known to be toxic to non-ta rget terrestrial plants based on available data.20 Prosulfuron and its degradates are mobile and may occur in aquatic systems. In addition, prosulfuron is stable in aquatic environments (except at low pHs). Therefore prosulfuron and its degradates may pose a risk to aquatic organisms. Toxi city studies suggest t hat this risk may be greatest to aquatic plants.

The available data do not suggest that prosulfu ron is particularly toxi c to aquatic animals. However, the chemical's persist ence and effect on aquatic and te rrestrial plants could affect primary productivity and, in tur n, have secondary effects on the entire animal community.

6.2. Conceptual Diagram

The conceptual model depicts the potential pathways for ecological risk associated with the use of prosulfuron for the control of weeds in co rn, popcorn, grain sorghum (milo), wheat, barley, rye, oats, triticale, proso millet, and small grains . The conceptual model provides an overview of the expected exposure routes for terre strial and aquatic organisms.

The potential exposure pathways and effects of pr osulfuron on aquatic environments are depicted in Figure 1 and for terrestrial environments in Figure 2

. Figure 3 depicts potential exposure from drinking water and inhalati on to terrestrial vertebrates and invertebrates. Stressors of concern for aquatic and terrestrial organisms in clude prosulfuron and the following degradates: CGA-159902 

### , CGA-150829, C GA-300406, CGA-325025, 

### CGA-325030, CGA-325028, CGA-325026, CGA-325027 , CGA-188838, 

### NANC-CGA-159902, and G-28533 . Solid arrows depict the most likely routes of exposure and effects; dashed lin es depict potenti al routes of exposure that are not considered likely.

Prosulfuron will enter the environment via direct application to terrestrial environments when it is applied to field crops. It may move off site via spray drift, runoff, and leaching. Volatilization from moist soils is not expected to be a major route of exposure because the vapor pressure of prosulfuron is less than 10 -8 Torr. Additionally, the Screening Tool for Inhalation Risk (STIR) 4 version 1.0 (run January 26, 2012) indi cates that exposure via inhalati on is not likely to be a risk concern for birds and mammals (see Section 7.2 and Appendix D for further discussion). These results combined with the estimated atmospheric ha lf-life of less than two days indicate that long range transport in the vapor phase is not an exposure pathway of concern.

The low K ow indicates that prosulfuron is not likely to bioconcentrate or bioaccumulate in aquatic or terrestrial organisms. The K oc values range from 15.2 to 41.3 L/kg, and K d values range from 0.074 to 0.293 L/kg, indicating that pros ulfuron is mobile. Because it is also persistent, prosulfuron has the potential to le ach to groundwater and to reach surface water by runoff and spray drift.

The Screening Imbibition Program (SIP) 6 version 1.0 (run January 26, 2012) indicates that prosulfuron has the potential to be present in drinking water at high enough concentrations to result in acute and chronic risks of concern for both birds and mammals ( Appendix E for results output). This is a highly conservative evalua tion since estimated drinking water exposure is unrelated to applications rate; rather, SIP assume s that concentrations in drinking water could be

4 http://www.epa.gov/oppefed1/models/terrestrial/index.htm21 at the level of solubility.

Finally, surface and shallow ground water contaminated with prosulfuron have the potential to be used as irrigation water, which may result in exposu re to terrestrial plants. Prosulfuron is toxic to terrestrial plants and there are also incident da ta substantiating potential for risks to terrestrial plants.

Figure 1. Conceptual model depicting stresso rs, exposure pathways, and potential effects to aquatic organisms from the use of prosulfuron on crops.22 Figure 2. Conceptual model depicting stresso rs, generic exposure pathways, and potential effects to terrestrial organisms (terrestrial plants, terrestrial invertebrates, and dietary routes of exposure for terrestrial vertebrates) fr om the use of prosulfuron on various crops.23 Figure 3. Conceptual model depicting stressors , drinking water and inhalation exposure pathways, and potential effects to terrestrial anim als from the use of prosulfuron on crops.

7. Analysis Plan

In order to address the risk hypot hesis, the potential for advers e effects on the environment is estimated. The use, environmental fate, and ecol ogical effects of prosul furon are characterized and integrated to assess the risks. This is acco mplished using a risk quotient (ratio of exposure concentration to effects concentr ation) approach. Although risk is often defined as the likelihood and magnitude of adverse ecological effects, the risk quotient-based approach does not provide a quantitative estimate of likelihood an d/or magnitude of an adverse effect. However, as outlined in the Overview Document (USEPA, 2004), the li kelihood of effects to individual organisms from particular uses of prosulfuron is estimat ed using the probit dose-re sponse slope and either the level of concern (discussed below) or actual calculated risk quotient value.

This analysis plan will be revisited and may be revised depending upon the information submitted by the public in response to the opening of the Registration Review docket for prosulfuron.24 7.1. Identification of Stressors of Concern

The Health Effects Division (HED) did not identify any degradates of human health concern in its latest risk assessment of prosulfuron (USEPA, 2009). In EFED’s upcoming Registration Review Ecological Risk Assessment of prosul furon, all 11 major and minor degradates of prosulfuron described in section 3.3 will be cons idered potential stressors of concern for the following reasons (see Appendix A3 for structure, identity, and fate information on transformation products). Based on environmental fa te data, it is possible that both parent and degradates may move to adjacent terrestrial areas or surface waters near the site of application, creating the potential for non-target organisms to be exposed. In addition, all degradates retain one or more of the major structural properties of the parent ( e.g. , SU bridge; triazine heterocyclic ring structure) and therefore may exhibit similar t oxicity to the parent. No new data is currently recommended to better understand the potential ecological effects of degradates. Instead, a total toxic residues (TTR) approach wi ll be employed during risk asse ssment, where exposure values ( i.e. , EECs) of parent and degradates will be su mmed and subsequently compared to toxicity endpoints for the parent in order to estimate a cumulative risk valu es (called “risk quotients”) for parent plus degradates. The risk quotient will th en be compared to Agency levels of concern (LOCs) for the appropriate group of organisms (see Appendix F for LOC values). The specific set of degradates that will be used in the TTR approach will depend on the organismal group being examined as outlined below.

No toxicity data are availabl e in EPA databases or in the open literature for any of the prosulfuron degradates identified in environm ental fate studies. Therefore, information on degradate molecular structure as well as quant itative structure-activity relationships (QSAR) were used to determine whether additional toxici ty data are needed for transformation products to address critical uncertainties.

Terrestrial Plants

In the absence of laboratory toxicity data, a ny degradate containing th e intact SU bridge ( i.e.
, -NH-CO-NH-SO2-) would ideally be included as pa rt of a TTR approach for terrestrial plants. This includes the following degradates: CGA-300406, CGA-325025, CGA-325026, CGA-325028, CGA-325030, NANC-C GA-159902, CGA-273437. Degradates not containing the SU bridge are assumed to be non-toxic and w ould not be included in risk estimation. Although several triazine-type products do result from br eakdown of the parent, these degradates do not have the two n-alkyl groups that are characteristic of herbic idally active triazine compounds ( e.g ., atrazine). Under the TTR scenario laid out, combined EECs would be calculated for parent and SU degradates and then compared to terrestrial plant toxicity endpoints in order to calculate risk quotients. However, EFED does not currently have a method for calc ulating terrestrial EECs for degradates. Therefore, the TTR approach for terrestrial plants will only be employed if methods become available prior to the upcom ing Registration Review risk assessment.

Aquatic Plants

QSAR analysis was conducted in ECOSAR (version 1.00) 5 and indicates that degradates

5 http://www.epa.gov/oppt/newchems/tools/21ecosar.htm25 retaining the SU bridge may be toxic to green algae ( Table 9 ). In the absence of additional toxicity data for degradates, tr ansformation products identified as SUs will be assumed to be as toxic as the parent to both vasc ular and nonvascular aquatic plants. Thus, a TTR approach will be applied in a similar manner as described for terr estrial plants. It should be noted that there is uncertainty associated with structure-activity estimates for green algae since calculations in ECOSAR were based on empirical EC 50 values from only three SU chemicals 6 . However, empirical and predicted EC 50 values for the parent compound are similar (0.01 and 0.05 mg ai/L, respectively), providing some support for using QS AR to predict toxicity to aquatic plants. Degradates not falling into the SU category (CGA-159902; C GA-325027; G-28533; CGA18838) will not be included in risk estimation of aquatic plants. European Union (EU) data available through the FOOTPRINT database 7 on toxicity of CGA-159902 (does not retain SU bridge) to green algae suggest s that it is several orders of magnitude less toxic (EC 50 86 mg/L) than the parent.

Aquatic Animals

For aquatic animals ( i.e. , fish, daphnids), QSAR appears to overestimate the toxicity of prosulfuron by several orders of magnitude rela tive to empirical data regardless of compound class ( Table 9 ). Consequently, toxicity predictions from ECOSAR may not be reliable for prioritizing degradates. Given this uncertaint y, a TTR approach will be applied to aquatic animals across all prosulfuron degradates unless additional toxicity data becomes available. The use of a TTR approach across degradates for aq uatic animals is justified for several reasons. First, all 11 degradates under consideration fall into at least one of the three chemical classifications of the parent (i.e., triazine s, amides, sulfonyl ureas). Second, ECOSAR predictions do not suggest that a ny degradate is markedly more toxic than the parent. Finally, empirical toxicity data from the EU FOOTPRINT database 7 for transformation products CGA159902, CGA-150829, CGA-300406, and CGA-349707 re port fish and/or daphnid EC 50 values ranging from 16 to 200 mg/L, which are all within one order of magnitude of empirical endpoint values from the parent compound. There is some uncertainty regardi ng acute toxicity of degradate CGA-150829 to daphnids (EC 50 16 mg/L) based on EU data, which is substantially lower than parent toxicity for the same species (EC 50 >120 mg/L); however, since the peak water column EEC for CGA-150829 is likely to be more than 20 times lower than 16 mg/L, it is unlikely that additional aquatic animal data for CGA-150829 would trigger risks of concern ( i.e., exceed aquatic animals listed species LOC of 0.05).

Table 9. ECOSAR Quantitative Structure-Ac tivity Relationship (QSAR) Toxicity Predictions for Prosulfuron and Degradates

Compound (compounds class used by ECOSAR) Estimated Toxicity Endpoint (mg/L)

96-hr FW fish

EC 50 /LC 50 48-hr Daphnid

LC 50 96-hr EC 50 Green Algae Fish Chronic Value Daphnid Chronic

Value EMPIRICAL TOXICITY DATA Prosulfuron Parent (measured) >155 >120 0.0106 149 148

6 ECOSAR v1.00 User Guide provides a list of all data points used to generate QSAR estimates

7 EU data has not been evaluated by EPA and is only used here for degradate prioritization. http://sitem.herts.ac.uk/aeru/footprint/en/26 Compound (compounds class used by ECOSAR) Estimated Toxicity Endpoint (mg/L)

96-hr FW fish

EC 50 /LC 50 48-hr Daphnid

LC 50 96-hr EC 50 Green Algae Fish Chronic Value Daphnid Chronic

Value ECOSAR TOXICITY PREDICTIONS Prosulfuron (Parent) Triazines 2.3 4.6 3.8 1.4 0.97 Amides 3.1 3.0 0.34 0.019 0.040 Sulfonyl Ureas N/A 7.9 0.047 N/A 0.84 CGA-159902 Amides 18 12 0.46 0.11 0.15 CGA-150829 Anilines: Aromatic Amines 49 1.9 7.7 0.21 0.036

Triazines 474 171 31 44 12 CGA-300406

Phenols 26 11 48 2.2 (30-days) 0.012 (60days) 2.1

Triazines 42 39 16 11 5.0 Amides 21 14 0.64 0.12 0.18 Sulfonyl Ureas N/A 42 0.045 N/A 4.2 Phenol Amines 9.9 1.9 4.5 0.33 0.29 CGA-325025 Anilines: Aromatic Amines 31 3.0 17 0.074 0.039

Triazines 40 37 15 10 4.8 Amides 20 13 0.63 0.12 0.18 Sulfonyl Ureas N/A 40 0.045 N/A 4.1 CGA-325028 Imides 13 16 2.1 1.2 1.5 Amides 5.5 4.7 0.39 0.033 0.062 Sulfonyl Ureas N/A 13 0.043 N/A 1.3 CGA-325026 Imides 96 105 5.1 9.4 8.5 Amides 42 24 0.74 0.25 0.32 Sulfonyl Ureas N/A 76 0.038 N/A 7.4 CGA-325027 Amides 49 26 0.71 0.29 0.35 G-28533 Triazines 1235 334 48 83 20 Phenols 54 383 1.4 20 153 NANC-CGA-159902 Imides 69 78 4.6 6.8 6.5 Amides 30 19 0.69 0.18 0.25 Sulfonyl Ureas N/A 58 0.041 N/A 5.7 CGA-18838 Anilines: Aromatic Amines 157 2.7 8.8 1.1 0.072

Phenols 388 69 376 16 (30day) 0.004 (60-day) 13

Triazines 8264 1331 122 317 59 Phenol Amines 24 1.4 10 2.2 1.1 CGA-325030 Imides 7.4 9.3 1.7 0.71 0.9427 Compound (compounds class used by ECOSAR) Estimated Toxicity Endpoint (mg/L)

96-hr FW fish

EC 50 /LC 50 48-hr Daphnid

LC 50 96-hr EC 50 Green Algae Fish Chronic Value Daphnid Chronic

Value Amides 3.2 3.1 0.34 0.019 0.040 Sulfonyl Ureas N/A 8.0 0.047 N/A 0.85 CGA-273437 Triazines 142 96 30 26 10 Benzyl Alcohols 98 22 N/A 6.5 7.2 Amides 47 27 0.90 0.28 0.36 Sulfonyl Ureas N/A 86 0.049 N/A 8.5

7.2. Measures of Exposure

In order to estimate risks of prosulfuron exposur e in aquatic and terres trial environments, all exposure modeling and resulting risk conclusion s will be based on maximum application rates and methods cited in Table 1 and will be estimated for each use of prosulfuron. Measures of exposure are based on aquatic a nd terrestrial models that pr edict estimated environmental concentrations (EECs) of prosulfuron.

Concentrations of prosulfuron in surface waters (EECs) will be estimated using PRZM (Pesticide Root Zone Model version 3.12.2; May 12, 2005) and EXAMS (Exposure Analysis Modeling System version 2.98.04.06; April 25, 2005). The PR ZM model simulates pesticide movement from and transformation on an agricultural fi eld following application. The EXAMS model simulates resulting concentrati ons in a receiving water body. The PRZM and EXAMS models and their user manuals may be downloaded from the EPA Water Models web-page (US EPA, 2006). Percent Cropped Area (PCA) adjustment f actors are used to account for the maximum fractional area within a watershe d that may be planted with a modeled crop, and are used to modify drinking water concentrations pred icted by PRZM and EXAMS (US EPA, 2010).

Concentrations of prosulfuron in ground water will be estimated using EFED's Tier I aquatic model SCIGROW (Screening Concentration In Ground Water, version 2.3; 8/8/2003). SCIGROW is a regression model us ed as a screening tool to es timate pesticide concentrations found in ground water used as drinking wate r. The output of SC IGROW represents concentrations that might be expected in sh allow unconfined aquifers under sandy soils, and therefore represents ground water that is most potentially vulnerable to pesticide contamination. The SCI-GROW model and user’s manual may also be downloaded from the EPA Water Models web-page (US EPA, 2006).

In addition to modeling estimates, available monitoring data will be evaluated. Monitoring data will include those collected/reported by states as well as other federal departments/agencies ( e.g ., USGS National Water Quality Assessment; http://water.usgs.gov/nawqa)

.
A downstream dilution model (under development) may be used to identify areas downstream from a use area that may have EECs high enough to re sult in a risk concern. This analysis will be used to define the potential area of effects for endangered species.28 Exposure estimates for terrestrial an imals assumed to be in the target area or in an area exposed to spray drift are derived using th e T-REX model (version 1.4.1, 10/09/2008) 4 . This model incorporates the Kenaga nomogr aph, as modified by Fletcher et al. (1994), which is based on a large set of field residue data . The upper-limit values from th e nomograph represent the upper bound of residue values from actual field meas urements (Hoerger and Kenaga, 1972). The Fletcher et al. (1994) modifications to the Kenaga nomograph are based on measured field residues from 249 published research papers, incl uding information on 118 species of plants, 121 pesticides, and 17 chemical classes (Fletcher et al., 1994). Based on these data, T-REX assumes a 35-day foliar dissipa tion half-life in the absence of other data.

EECs for terrestrial plants inhabiting dry and wetland areas are derived using the program TERRPLANT (version 1.2.2, 12/26/2006) 4 . This model uses estimates of pesticides in runoff and spray drift to calculate EECs. EECs ar e based upon solubility, application rate and minimum incorporation depth. AgDRIFT may also be used to assess exposure to spray drift.

In order to determine if inhalation is a potential pathway of concern for terrestrial organisms, the Screening Tool for Inhalation Risk (STIR v.1.0) was used to calculate an upper-bound estimate of exposure using prosulfuron’s vapor pressure and molecular weight fo r vapor phase exposure as well as the maximum application rate and method of application for spray drift. STIR incorporates results from several toxicity studies including acute oral (MRID 426852-15; LD 50 546 mg/kg-bw) and inhalation (MRID 426852-17; LC 50 5.5 mg/L) rat to xicity endpoints obtained from the "six-pack" of core studies submitted to OPP’s Registration Division for technical and formulated products of a pesticide as well as the most sensitive acute oral avian toxicity endpoint. Based on the results of the STIR model, inhalation exposure alone was not determined to be a potential pathway of con cern for avian or mammalian species on an acute exposure basis (STIR program inputs/output s for prosulfuron are provided in Appendix D ). The analysis of the inhalation route in STIR does not consider that aggregation with other exposure pathways such as dietary, dermal, or drinking wa ter may contribute to a total exposure that has a potential for effects to non-target animals. Ho wever, the Agency does consider the relative importance of other routes of expos ure in situations where data i ndicate that pesticide exposures through other routes may be potentially significan t contributors to wildlife risk (USEPA, 2004). The risk assessment will discuss the impact of consideration of other r outes of exposure that have been identified as potentially important and the degree of certainty associated with screening-level risk assessment conclusions. De tailed information about STIR v.1.0, as well as the tool, can be found on the EPA's website. 8

The Screening Imbibition Program (SIP v.1.0) was used to calculate an upper-bound estimate of exposure based on the solubility of prosulfuron as well as the most sensitive acute and chronic avian and mammalian toxicity endpoints (see Table 8 ). Drinking water exposure was determined to be a potential pathway of concern for both avian and mammalian species on an acute and chronic exposure basis (SIP program input s/outputs for prosulfuron are provided in Appendix E ). As stated previously, this is a highly c onservative evaluation since estimated drinking water exposure is unrelated to applica tions rate; rather, SIP assumes th at concentrations in drinking water could be at the level of solubility. Th is pathway will be explored further with the29 development of SIP v.2.0 in the risk assessment fo r prosulfuron. Detailed information about the SIP v.1.0 as well as the tool can be found on EPA's website. 8

Two spray drift models, AgDISP and AgDRIFT, ar e used to assess exposures of aquatic and terrestrial organisms to prosulfuron deposited in terrestrial and aquatic ha bitats by spray drift. AgDrift (version 2.01; dated 5/24/2 001) is the model most commonly used to simulate spray drift into terrestrial and aquatic environments. AgDISP (v ersion 8.13; dated 12/14/2004) (Teske and Curbishley, 2003) is used when a parameter n eeds to be modeled that is not available in AgDRIFT. Spray drift analysis will be an important part of the analysis in defining the potential area of effects for endangered species.

7.3. Measures of Effects

Ecological effects data are used as measures of di rect and indirect effect s to biological receptors. Effects data are obtained from registrant-submitted studies or from literature studies identified by the ECOTOX database. The acute measures of eff ect used for animals in this assessment are the LD 50 , LC 50 and EC 50 . LD stands for "Lethal Dose", and LD 50 is the amount of a material, given all at once, that is estimated to cause the deat h of 50% of the test organisms. LC stands for "Lethal Concentration" and LC 50 is the concentration of a chemical that is estimated to kil1 50% of the test organisms. EC stands for "Effect Concentration" and the EC 50 is the concentration of a chemical that is estimated to produce a specific effect in 50% of the te st organisms. Endpoints for chronic measures of exposure for listed and non-listed animals are the NOAEL/NOAEC. NOAEL stands for "No Observed-Adverse-Effect-Level " and refers to the hi ghest tested dose of a substance that has been reported to have no ha rmful (adverse) effects on test organisms. The NOAEC ( i.e ., "No-Observed-Adverse-Effect-Concentration" ) is the highest test concentration at which none of the observed effects were statisti cal1y different from the control. For non-listed plants, only acute e xposures are assessed ( i.e ., EC 25 for terrestrial plants and EC 50 for aquatic plants); for listed plants either the NOAEC or EC 05 is used.

Where available, sublethal effects observed in both registrant-submitted and open literature studies wil1 be evaluated qualitatively. Such effects may include behavioral changes ( e.g ., lethargy and changes in coloration). However, qua ntitative assessments of risks are limited to those endpoints that can be di rectly linked to the Agency's assessment endpoints of impaired survival, growth and reproduction.

In the absence of taxa-specific data, the assessm ent of risk for direct effects to non-target organisms makes the assumption that toxicity of prosulfuron to birds is similar to terrestrialphase amphibians and reptiles. The same assu mption is made for fish and aquatic-phase amphibians. In the absence of data for either acute or chronic effects, the conservative assumption wil1 be to presume that prosulfuron is toxic.

8 http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial30 7.4. Integration of Exposure and Effects

Risk characterization is the inte gration of exposure and ecological effects characterizations to determine the potential ecological risk from the registered uses of prosulfuron and the likelihood of direct and indirect effects to non-target or ganisms in aquatic and terrestrial habitats. The exposure and toxicity (effects) da ta are integrated in order to evaluate the risks of adverse ecological effects on non-target sp ecies. For the assessment of prosulfuron, the risk quotient (RQ) method is used to compare exposure and measured toxicity values. EECs are divided by acute and chronic toxicity values . The resulting RQs are then compared to the Agency's Levels of Concern (LOCs) (USEPA 2004) ( Appendix F ). These criteria are used to indicate when prosulfuron use, as directed on the labels, has th e potential to cause adve rse direct or indirect effects to non-target organisms. In addition, inci dent data from the EIIS will be considered as part of the risk characterization.

7.5. Deterministic and Probabilistic Assessment Methods

The quantitative assessment of risk will primarily depend on the deterministic point-estimate (RQ) based approach described in the risk assessment. Dependi ng on the extent of refinement needed by the risk manager, risk estimates may be further refined using pr obabilistic tools that the Agency has developed. These tools have b een reviewed by FIFRA Scientific Advisory Panels 9 and have been deemed as an appropria te means of refining assessments where deterministic approaches have identified risks. Ne wer tools may be available to assess the routes of exposure and will be applied as appropriate in Registration Review.

7.6. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA s ection 408(p), Prosulfuron is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal

9 http://vvww.epa.gov/scipoly/sap/index.htm31 systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredients and 9 inert ingredients. Prosulfuron is not among the group of 58 pesticide active ingredient s on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for Prosulfuron. For further information on the status of the EDSP, the policies and procedur es, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screen ing battery, please visit our website: http://www.epa.gov/endo/

.
7.7. Endangered Species Assessment

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to Federally-listed th reatened and/or endangere d (listed) species from registered uses of prosulfuron. This assessm ent will be conducted in accordance with the Overview Document (USEPA, 2004), provisions of the ESA, and the Services’ Endangered Species Consultation Handbook (USFWS/NMFS, 1998).

The action area is used to identify all listed (t hreatened and endangered) species and designated critical habitat that could be affected by the Federal action. The Federal action is the authorization or registration of pesticide use or uses as descri bed on the label(s) of pesticide products containing a particular active ingredient. The action area is defined by the Endangered Species Act as, “all areas to be affected directly or indirec tly by the Federal action and not merely the immediate area involved in the action” (50 CFR §402.2). Based on an analysis of the Federal action, the action area is defined by the actual and pote ntial use of th e pesticide.

In the case of nationwide ecological risk assessment conducted for prosulfuron under Registration Review, the action area will encompass the entire United States and its territories. The purpose of defining the action area as the entire US and its territories is to ensure that the initial area of consideration encompasses all ar eas where prosulfuron may be used now and in the future, including the potential for off-site transport via spra y drift and downstream dilution. Additionally, the concept of a na tionwide action area takes into acc ount the potential for direct and indirect effects and any poten tial modification to critical ha bitat based on ecological effect measures associated with reduction in survival, growth, and reproduction, as well as the full suite of sublethal effects available in the effects literatu re. It is important to note that the nationwide action area does not imply that dire ct and/or indirect e ffects and critical ha bitat modification are expected to or are likely to occur over the full ex tent of the action area, but rather to identify all listed species and critical habita t that may potentially be affected by the action. The Agency will use more rigorous analysis including consideratio n of available land cover data, toxicity data, and exposure information to determine areas wh ere individual listed species and designated32 critical habitat may be affected or modified via endpoints associated with reduced survival, growth, or reproduction.

7.8. Drinking Water Assessment

In order to bring the drinking wate r exposure assessment up to date with current data, models and simulation model guidance, a new drinking water assessment will be conducted to support future human health dietary risk assessments of prosulfuron. The drinking water exposure assessment will be conducted for the maximum labeled use rate in support of the human health dietary risk assessment. The drinking water assessment will incorporate model estimates of prosulfuron alone in surface water and ground water including any residues that are determined to be of toxicological concern (see Section 7.1). Concentrations of prosulfuron in surface water (EDWCs) will be estimated using PRZM 3.12.2 (dated May 12, 2005) and EXAMS 2.98.04.06 (dated April 25, 2005) coupled th rough the input shell PE 5.0 (US EPA, 2006). An EDWC of prosulfuron in ground water will be estimated using SCIGROW 2.3 (dated August 8, 2003).

8. Preliminary Identification of Data Gaps

8.1. Environmental Fate

The studies submitted to fulfill environmental fate data requirements for prosulfuron are fairly complete and therefore, additional studies are not necessary at this time. However, there is limited environmental fate data on degradates that can potentially impact water sources (CGA159902, CGA-150829, CGA-325030, CGA-188 838, G-28533, CGA-325025, CGA-325026, CGA-325027, CGA-325028, NANC-C GA-159902, and CGA-300406) due to leaching and/or runoff potential. Table 9 summarizes the fate data requirements for prosulfuron.

Table 10. Summary of Submitted Environmenta l Fate Studies, Study Classifications and Data Gaps for Prosulfuron and Its Degradates

Guideline MRID (part of the molecule that

was radiolabeled) Study Classification Comments on Study Classification Data Gap Comments

Hydrolysis 835.2120 (161-1) 42685246 (triazine) Acceptable None

No 42685247 (phenyl) Acceptable None

Aqueous Photolysis 835.2370 (161-2) 42685248 (triazine) Acceptable None

No The proposed degradation pathway

was not reported. 42685249 (phenyl) Acceptable None

Soil Photolysis 835.2410 43159327 (phenyl) Acceptable None No None33 Guideline MRID (part of the molecule that

was radiolabeled) Study Classification Comments on Study Classification Data Gap Comments

(161-3) 43159328 (triazine) Acceptable None

Aerobic Soil Metabolism

835.4100 (162-1) 42685250 (triazine) Acceptable None

No None 42685251 (phenyl) Acceptable None

43387712 (triazine) Acceptable None

43387713 (phenyl) Acceptable None

Anaerobic Soil

Metabolism

835.4200 (162-2) 42685252 (triazine) Acceptable None

No None 42685253 (phenyl) Supplemental Deficiencies were found in the study. Degradates isolated from soil (6.6% of the applied radioactivity) were not identified. In addition, the concentration of the individual compounds isolated using HPLC do not sum the concentration

of total residues in the soil extracts determined using Liquid Scintillation Counting.

43387714 (triazine) Acceptable None

43387715 (phenyl) Acceptable None

Aerobic Aquatic

Metabolism

835.4300 (162-4) 43387718 (triazine) Acceptable None

No None 43387719 (phenyl) Acceptable None

Anaerobic

Aquatic Metabolism

835.4400 (162-3) 43387716 (triazine) Acceptable None

No None 43387717 (phenyl) Acceptable None

Adsorption/deso

rption batch 42685257 (triazine) Acceptable Conducted on parent compound No None34 Guideline MRID (part of the molecule that

was radiolabeled) Study Classification Comments on Study Classification Data Gap Comments

equilibrium

835.1230 43159329 (phenyl) Acceptable Conducted on degradate CGA-159902

43159330 (phenyl) Supplemental Conducted on degradate CGA-300406. Theconcentration of CGA300406 used in the test solutions (0.25 to 0.99 μg/mL) had a four-fold

range. In order for Freundlich values to beaccurately assessed a tenfold of concentrations should be tested

43387720 (triazine) Acceptable Conducted on degradate G-28533

Aged Column

Leaching 835.1240 (163-1) 42685255 (triazine) Acceptable None

No None 42685256 (phenyl) Acceptable None

Soil Column

Leaching (unaged) 42685257 42685254 (triazine) Acceptable None No None

Terrestrial; Field Dissipation

835.6200

Terrestrial; Field Dissipation

835.6200 43159331 Acceptable Cold study conducted in Iowa

No None 43159332 Acceptable Cold study conducted in Georgia

43387721 Acceptable (supplement to MRID 43159331) Cold study conducted in Iowa

43387722 Acceptable (supplement to MRID 431593332) Cold study conducted in Georgia

43387724 Acceptable Radiolabeled study performed in Kentucky

No None 43387725 Acceptable Radiolabeled study performed in North Carolina

43387726 Acceptable Storage stability (Kentucky)35 Guideline MRID (part of the molecule that

was radiolabeled) Study Classification Comments on Study Classification Data Gap Comments

43387727 Acceptable Storage stability (North Carolina)

44449202 Not reviewed The study was submitted April 7, 1998 --- Dissipation of Prosulfuron in Soil Under Field Conditions With and Without Winter Wheat in Kansas
Bioconcentration Factor 850.1730 Not applicable None No None

8.2. Ecological Effects

Several ecological effects studies on prosulfuron are needed to bette r assess the potential risk of exposure to non-target organisms. Tables 10 and 11 summarize the data that have been submitted for the parent compound and highlight existing data gaps. The following studies are recommended to decrease uncertainty in risk es timation and characteriza tion of prosulfuron:

• Tier II Terrestrial Plant Seedling Em ergence (850.4225) and Vegetative Vigor (850.4250) Toxicity Studies with TEP [2 Studies]

In the Tier II terrestrial pl ant studies that were previ ously conducted (MRIDs 429747-01; 429497-10), plants were exposed to technical grade active ingredient (TGAI) instead of a typical end-use product (TEP), which is recommende d in 40 CFR Part 158 and in OCSPP terrestrial plant toxicity test guidelines. Formulated pr oducts may contain adjuva nts and/or surfactants which are intended to increase the efficacy of the compound, but may also increase exposure and/or toxicity to non-target organisms as well. Therefore, it is recommended that additional tests be conducted with TEP.

• Special Study for Non-Target Plant Repro ductive Toxicity (Non-Guideline) for TEP [1 Study]

Terrestrial plants are typically very sensitive to sulfonylurea ur ea herbicide exposure. There is evidence to suggest that plant re production may be affected by su lfonylurea herbicides at levels below effects on vegetative growth or visual injury (Fletcher et al ., 1993). Uncertainty regarding the potentially greater sensitivity of terrestrial pl ant reproduction has been discussed extensively in the environmental fate and effects asse ssment supporting the Rere gistration Eligibility Decision (RED) for chlorsulfuron (US EPA, 2003). Plants form the basis of most habitats and contribute significantly to overa ll environmental quality. The loss of plant reproductive output could potentially have an advers e effect on animals, both inverteb rates and vertebrates, as many36 are dependent on plant reproduction as a source of food and habita t. A solid understanding of the potential risks to plants is theref ore essential. To the extent that terrestrial plant reproduction is more sensitive to prosulfuron than growth e ndpoints, risks to terrestrial plants may be underestimated in the risk assessment. Additiona l information on the reproductive toxicity of prosulfuron to terrestrial plants is necessary to address this uncertainty.

• Avian Acute Oral Toxicity Test with a Passerine Species (850.2100) [1 Study]

According to 40 CFR 158.630, acute or al toxicity data are now requi red for a passerine species. No acute oral toxicity data relate d to prosulfuron have been identif ied in the scientific literature (using ECOTOX). Although available acute oral toxic ity data for birds indicate that prosulfuron is classified as slightly toxic to practically non -toxic to other bird species, several mortalities and/or sublethal effects were obs erved in acute oral toxicity st udies with other avian species (MRIDs 426852-05, 426852-06). Since passerines ma y potentially be more sensitive to prosulfuron than other avian taxa, an acu te oral toxicity study is recommended.

Table 11. Summary of Submitted Aquatic a nd Terrestrial Animal Effects Studies and Data Gaps for Parent Prosulfuron.

Guideline Description—Test Substance MRID(s) Study Classification Data Gap Comments

Avian and Mammalian Testing

850.2100 Avian acute oral toxicity, waterfowl—TGAI 426852-05 Acceptable No

850.2100 Avian acute oral toxicity, upland game bird species— TGAI 426852-06 Acceptable No Non-definitive endpoint is acceptable at current maximum application rate of 0.0356 lbs ai/A †

850.2100 Avian acute oral toxicity, passerine species—TGAI None N/A Yes Part of data requirements as of December 2007 to

address passerine sensitivity concerns

850.2200 Avian dietary toxicity, waterfowl species—TGAI 426852-07 Acceptable No Non-definitive endpoint is acceptable at current maximum application rate of 0.0356 lbs ai/A †

850.2200 Avian dietary toxicity, upland game bird—TGAI 426852-08 Acceptable No Non-definitive endpoint is acceptable at current maximum application rate of 0.0356 lbs ai/A †

850.2300 Avian reproduction, waterfowl species—TGAI 429497-01 Acceptable No

850.2300 Avian reproduction, upland game bird species—TGAI 429497-02 Unacceptable No Data requirement previously waived

850.2400 Wild mammal toxicity—TGAI None N/A No Not triggered based on ecotoxicity data, predicted EECs, fate properties, and use pattern criteria.37 Guideline Description—Test Substance MRID(s) Study Classification Data Gap Comments

850.2500 Simulated or actual field testing—TEP None N/A No Not triggered based on ecotoxicity data, predicted EECs, fate properties, and use pattern criteria.
Aquatic Animal Testing

850.1010 Freshwater invertebrate, acute toxicity—TGAI 426852-11 Acceptable No Non-definitive endpoint is acceptable since no mortalities or sublethal effects occurred

850.1025 Estuarine/Marine Mollusk acute toxicity—TGAI 432126-02 Acceptable No Non-definitive endpoint is acceptable since no mortalities or sublethal effects occurred

850.1035 Estuarine/Marine crustacean acute toxicity—TGAI 432126-01 Acceptable No Although mortality was observed during limit test,

additional data are not recommended

850.1075 Freshwater fish, acute toxicity, warm water species—TGAI 426852-09 Acceptable No Non-definitive endpoint is acceptable since no mortalities or sublethal effects occurred

850.1075 Freshwater fish, acute toxicity, cold water species—TGAI 426852-10 Acceptable No Non-definitive endpoint is acceptable since no mortalities or sublethal effects occurred

850.1075 Estuarine/Marine fish acute toxicity—TGAI 429497-06 Acceptable No

850.1300 Freshwater invertebrate, reproduction test—TGAI 429497-08 Acceptable No

850.1350 Estuarine/marine invertebrate, reproduction test—TGAI None N/A No A chronic invertebrate lifecycle toxicity test is not triggered according to 40 CFR 158

850.1400 Freshwater fish, early life stage test—TGAI 429497-07 Acceptable No

850.1400 Saltwater fish, early life stage test—TGAI None N/A No A fish early life stage toxicity test is not triggered

according to 40 CFR 158

850.1500 Freshwater fish lif e cycle test None N/A No Data requirement not triggered EEC <0.1 of NOAEC from

freshwater fish ELS and daphnid life cycle tests38 Guideline Description—Test Substance MRID(s) Study Classification Data Gap Comments

850.1500 Estuarine/marine Fish life cycle
test None N/A No Data requirement not triggered EEC <0.1 of NOAEC from

freshwater fish ELS and daphnid life cycle tests

850.1950 Simulated or actual field testing for aquatic organisms None N/A No Higher tier testing to address risk uncertainties have not been identified at this time

Sediment Testing

850.1735 Whole sediment 10-d freshwater invertebrate—TGAI None N/A No Data requirement not triggered Half life >10 days K d <50 Log K OW <3 K OC <1,000

850.1740 Whole sediment 10-d estuarine/marine invertebrate— TGAI None N/A No Data requirement not triggered Half life >10 days K d <50 Log K OW <3 K OC <1,000

Agencywide guideline Whole sediment chronic freshwater and/or marine

invertebrate—TGAI None N/A No Data requirement not triggered:

K d <50 Log K OW <3 K OC <1,000 Benthic EEC <0.01 of acute LC 50 /EC 50 values

Insect Pollinator Testing

850.3020 Honeybee acute contact toxicity—TGAI 430800-47 Acceptable No

850.3030 Honeybee toxicity of residues on foliage—TEP None N/A No Data requirement not triggered

850.3040 Field testing for pollinators None N/A No Higher tier testing to address risk uncertainties have not been identified at this time

† These non-definitive endpoint values prohibit the ability to determine a definitive risk value. However, given the current maximum application rate (0.0365 lbs ai/A), di etary- and dose-based EECs calculated using TREX ver. 1.4.1, would be lower than these values, and the potential for acute risk is considered low. If higher outdoor spray application rates are identified, the adequacy of these non-definitive values to support a determination of low potential for acute risk would need to be re-evaluated.39 Table 12. Summary of Submitted Aquatic and Terrestrial Plant Effects Studies and Data Gaps for Parent Prosulfuron.

Guideline Description MRID Study Classification Data Gap Comments

850.4225

Tier II Seedling emergence (10 species)—TGAI 429747-01 Supplemental † Yes TGAI was used; TEP is recommended for terrestrial plant toxicity studies.

850.4250

Tier II Vegetative vigor (10 species)—TGAI 429497-10 Supplemental † Yes T GAI was used; TEP is

r ecommended for terrestrial plant
t oxicity studies.

N/A Seed germination (10 species)—TGAI 429497-09 Acceptable No TGAI was used; TEP is recommended for terrestrial plant toxicity studies

Nonguideline Terrestrial Plant Reproduction Study—TEP N/A None Yes Special study; see justification. TEP should be used.

850.4400

Tier I and/or II Tier II Aquatic plant growth, vascular plant — TGAI 429497-13 Acceptable No

850.5400

Tier I and/or II Tier II Aquatic Plant, freshwater green alga species—TGAI 429497-14 Acceptable No

850.5400

Tier I and/or II Tier II Aquatic Plant, freshwater diatom—TGAI 429497-15 Supplemental † No This study is downgraded to supplemental because of high variability in the data and a low starting cell count. However, a new study is not recommended.

850.5400

Tier I and/or II Tier I Aquatic Plant, marine diatom — TGAI 429497-12 Acceptable No <50% reduction in growth observed a limit dose. Also, the maximum peak EEC is more than 10 times lower than the limit concentration tested. Tier II testing is not recommended.

850.5400

Tier I and/or Tier II Tier II Aquatic Plant, cyanobacterium — TGAI 429497-11 Acceptable No <50% reduction in growth observed a limit dose. Also, the maximum peak EEC is more than 10 times lower than the limit concentration tested. Tier II testing is not recommended.

† Studies recently downgraded to “supplemen tal” based on current Agency standards.

Rationale for studies not being requested:

An avian reproduction study with the bobwh ite quail (MRID432635-01) was previously submitted to EPA for review and deemed “unacceptable.” The study was primarily rejected due to high control mortality in the parental birds. This study was later waived on the grounds that prosulfuron exhibits low toxicity to birds, and al so because application rates of the chemical at the time were low. Since application rates have not increased since the waiver was granted and no new data or incidents have been reported to demonstrate av ian toxicity, it is recommended40 that the waiver for this data requirement be extended into the current registration review period. However, additional data may be recommended in the future if proposed application rates increase from those currently on the labels.

An acute toxicity test with the estuarine/marine crustacean, Americamysis bahia (Mysidae), was previously submitted and considered “acceptable” (MRID 432126-01). However, it should be noted that multiple mortalities occurred in the treatment group exposed to prosulfuron. While there was less than 50% mortality at the limit dose, the study indicate s that there is a potential of mortality to non-target crustac eans from the exposure to this pe sticide. Based on the Agency’s current guidance, additional data is typically recommended when any mortality is recorded during a limit test. However, since the highe st preliminary surface water EEC value for prosulfuron (1.71 μg ai/L) is more than four orders of magnitude below the non-definitive LC 50 value (150,000 μg ai/L), it is unlik ely that additional study data w ould result in risks of concern for mysids at current application rates. Therefore, a definitive te st on mysid acute toxicity is not requested at this time, but may be recommende d in the future if proposed application rates increase from those currently on the labels.

An aquatic nonvascular plant toxicity test (MRID 429497-15) w ith the freshwater diatom Navicula pelliculosa was recently downgraded from “accepta ble” to “supplemental” and is not suitable for quantitative use in risk assessment. However, a new study is not being recommended at this time based on the following rationale: Co efficients of variati on in day 5 cell density ranged from 17 to 101 in treatment groups versus 59 in the control. This pr ecludes the ability to detect significant effects even when the deviation from the control is substantial (approximately 20-25% inhibition at the two highest concentrations tested were not statistically significant). However, the benefit of an additional study with the same species is likely to be low. A definitive NOAEC and EC 50 have been established for another freshwater species, Pseudokirchneriella subcapitata , and these values are expected to be lower (more sensitive) than any endpoints derived from an additional data submission for N. pelliculosa

.

9. References

9.1. Data Submitted To Support Registration

Avian Single Dose Oral Toxicity 42685205 Pedersen, C. (1992) CGA-152005 Technical: 14-Day Acute Oral LD50 Study in Mallard Ducks: Lab Project Number: 102-019-04. Unpublished study prepared by Bio-Life Assoc. Ltd. 48 p.
42685206 Pedersen, C. (1991) CGA-152005 Technical: 21 -Day Acute Oral LD50 Study in Bobwhite Quail: Lab Project Number: 102-004-03. Unpublished study prepared by Bio-Life Assoc. Ltd. 36 p.

Avian Dietary Toxicity 42685207 Pedersen, C. (1991) CGA-152005 Technical: 8-Day Acute Dietary LC50 Study in Mallard Ducklings: Lab Project Number: 102-002-02. Unpublished study prepared by Bio-Life Assoc. Ltd. 60 p.
42685208 Pedersen, C. (1991) CGA-152005 Technical: 8- Day Acute Dietary LC50 Study in Bobwhite Quail: Lab Project Number: 102-018-01. Unpublished study prepared by Bio-Life Assoc. Ltd. 63 p.

Avian Reproduction41 42949701 Pedersen, C.; DuCharme, D. (1993) CGA-152005 Technical: Toxicity and Reproduction Study in Mallard Ducks: Lab Project Number: BLAL NO. 102-017-08. Unpublished study prepared by Bio-Life Associates, Ltd. 948 p.
42949702 Pedersen, C.; DuCharme, D. (1993) CGA-152005 Technical: Toxicity and Reproduction Study in Bobwhite Quail: Lab Project Number: BLAL NO. 102- 016-07. Unpublished study prepared by Bio-Life Associates, Ltd. 708 p.
43263501 Hosmer, A. (1994) Response to EPA Data Evaluation Record for the Study: CGA-152005 Toxicity and Reproduction Study in Bobwhite Quail: Lab Project Number: ABR/94044. Unpublished study prepared by Ciba-Geigy Corp. 44 p.

Acute Toxicity to Freshwater Fish 42685209 Boeri, R.; Ward, T. (1991) Acute Flow-throu gh Toxicity of CGA 152005 (Technical) to the Bluegill Sunfish, (Lepomis macrochirus): Lab Project Number: 90163-CG. Unpublished study prepared by Envirosystems, Div. of Resource Analysts, Inc. 25 p.
42685210 Boeri, R.; Ward, T. (1991) Acute Flow-through Toxicity of CGA 152005 (Technical) to the Rainbow Trout, (Oncorhynchus mykiss): Lab Project Number: 900164-CG. Unpublished study prepared by Envirosystems, Div. of Resource Analysts, Inc. 24 p.
42949703 Boeri, R.; Ward, T. (1991) CGA-152005 Technical: Acute Flow-Through Toxicity of CGA-152005 to the Bluegill Sunfish, (Lepomis macrochirus): La b Project Number: 90163-CG. Unpublished study prepared by Envirosystems Division. 25 p.
42949704 Boeri, R.; Ward, T. (1991) CGA-152005 Technical: Acute Flow-Through Toxicity of CGA-152005 to the Rainbow Trout, (Oncorhynchus mykiss): Lab Project Number: 90164-CG. Unpublished study prepared by Envirosystems Division. 24 p.

Acute Toxicity to Freshwater Invertebrates 42685211 Boeri, R.; Ward, T. (1991) Acute Flow-through Toxicity of CGA 152005 (Technical) to the Daphnid, (Daphnia magna): Lab Project Number: 90165-CG. Unpublished study prepared by Envirosystems, Div. of Resource Analysts, Inc. 24 p.
42949705 Ciba-Geigy Corp. (1993) CGA-152005 Technical: A Supplement to Acute Flow-Through Toxicity of CGA 152005 to the Daphnid, Daphnia Magna: MRID No. 42685211. Unpublished study. 15 p.

Acute Toxicity to Estuarine/Marine Organisms 42949706 Boeri, R.; Ward, T. (1991) CGA-152005: Acute Flow-through Toxicity of CGA 152005 to the Sheepshead Minnow, Cyprinodon variegatus: Lab Project Number: 9199-CG. Unpublished study prepared by Ciba-Geigy Corp. 23 p.
43212601 Boeri, R.; Ward, T. (1991) Acute Flow-Through Toxicity of CGA-152005 to the Mysid, Mysidopsis bahia: Lab Project Number: 9198-CG. Unpublished study prepared by Envirosystems Division, Resource Analysts, Inc. 23 p.
43212602 Boeri, R.; Ward, T. (1991) Acute Flow-Through Toxicity of CGA-152005 to the Eastern Oyster, Crassostrea virginica: Lab Project Number: 91100-CG. Unpublished study prepared by Envirosystems Division, Resource Analysts, Inc. 24 p.

Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study 42949707 Ward, T. (1992) CGA-152005: Early Life-Stage Toxicity of CGA-152005 to the Fathead Minnow, Pimephales Promelas: Lab Project Number: 91133-CG. Unpublished study prepared by Envirosystems Division. 39 p.
42949708 Ward, T.; Boeri, R. (1992) CGA-152005: Chronic Toxicity of CGA-152005 to the Daphnid, Daphnia42 Magna: Lab Project Number: 91134-CG. Unpublished study prepared by Envirosystems Division. 36 p.

Acute oral toxicity in rats 42685215 Glaza, S. (1991) Acute Oral Toxicity St udy of CGA-152005 Technical in Rats: Lab Project Number: 10302700. Unpublished study prepared by Hazleton Wisconsin, Inc. 46 p.

Subchronic Oral Toxicity: 90-Day Study 42685232 Chow, E.; Morrissey, R. (1991) 90-day Dietary Rangefinding Study with CGA-152005 Technical in Rats: Final Report: Lab Project Number: F-00057. Unpublished study prepared by Ciba-Geigy Corp., Env. Health Ctr. 268 p.

2-generation repro in rata43159319 Greci, L.; Turnier, J. (1993) Final Report: A Two-Generation Reproduction Study in Rats with CGA152005 Technical: Lab Project Number: F-00082. Unpublished study prepared by Environmental Health Center. 882 p.

Aquatic plant growth 42949711 Hughes, J.; Alexander, M. (1993) The Toxicity of CGA-152005 to Anabaena flos-aquae: Growth and Reproduction of Aquatic Plants, Tier 1: Lab Project Number: B267-54-2. Unpublished study prepared by Malcolm Pirnie, Inc. 61 p.
42949712 Hughes, J.; Alexander, M. (1993) The Toxicity of CGA-152005 to Skeletonema costatum: Growth and Reproduction of Aquatic Plants, Tier 1: Lab Project Number: B267-54-5. Unpublished study prepared by Malcolm Pirnie, Inc. 61 p.

Seed germination/seedling em ergence and vegetative vigor 42949709 Chetram, R. (1992) CGA-152005: Tier 2 Seed Germination Non-Target Phytotoxicity Study Using CGA-152005: Lab Project Number: BL91-448. Unpublished study prepared by Pan-Agricultural Labs, Inc. 108 p.
42949710 White, T. (1992) CGA-152005: Tier 2 Vegetative Vigor Non-Target Phytotoxicity Study Using CGA152005: Lab Project Number: BL91-450. Unpublished study prepared by Pan-Agricultural Labs, Inc. 263 p.
42974701 Canez, V. (1992) Tier 2 Seedling Emergence Non-Target Phytotoxicity Study Using CGA-152005: Lab Project Number: BL91-449: 0805A4AH(MG-REPORTS): AL-91-126. Unpublished study prepared by Pan-Agricultural Labs, Inc. 273 p.

Aquatic plant growth 42949713 Hughes, J.; Alexander, M. (1993) The Toxicity of CGA-152005 to Lemna gibba G3: Growth and Reproduction of Aquatic Plants, Tier 2: Lab Project Number: B267-54-4. Unpublished study prepared by Malcolm Pirnie, Inc. 37 p.
42949714 Hughes, J.; Alexander, M. (1993) The Toxicity of CGA-152005 to Selenastrum capricornutum: Growth and Reproduction of Aquatic Plants, Tier 2: Lab Project Number: B267-54-1. Unpublished study prepared by Malcolm Pirnie, Inc. 38 p.
42949715 Hughes, J.; Alexander, M. (1993) The Toxicity of CGA-152005 to Navicula pelliculosa: Growth and Reproduction of Aquatic Plants, Tier 2: Lab Project Number: B267-54-3. Unpublished study prepared by Malcolm Pirnie, Inc. 35 p.

Honey bee acute contact43 42685212 Brantly, T. (1991) Contact Toxicity of CGA-152005 to the Honeybee (Apis mellifera): Lab Project Number: 109/21492/001: 109-001. Unpublished study prepared by Auburn Environmental Consulting & Testing. 13 p.

Hydrolysis 42685245 Phelps, W. (1993) Environmental Chemistry of CGA-152005: Lab Project Number ABR-93019. Unpublished study prepared by Ciba-Geigy Corp. 18 p.
42685246 Kesterson, A. (1993) Hydrolysis of (carbon 14)Triazine CGA-152005 at pH 5,7,9: Lab Project Number: 524: 3-91. Unpublished study prepared by PTRL East, Inc. 190 p.
42685247 Kesterson, A. (1993) Hydrolysis of (carbon 14)Phenyl CGA-152005 at pH 5,7, and 9: Lab Project Number: 551: 22-91. Unpublished study prepared by PTRL East, Inc. 121 p.

Photodegradation-water 42685248 Kesterson, A. (1993) Solution Photolysis of (Carbon 14)Triazine CGA-152005 in Natural Sunlight: Lab Project Number: 570: 69-91. Unpublished study prepared by PTRL East, Inc. 127 p.
42685249 Kesterson, A. (1993) Solution Photolysis of (carbon 14)Triazine CGA-152005 in Natural Sunlight: Lab Project Number: 569: 68-91. Unpublished study prepared by PTRL East, Inc. 125 p.
43387710 Cruz, S. (1994) Measurement of the Ultraviolet Absorbance of CGA-152005 Degradates: Lab Project Number: ARB-94026: 184-94. Unpublished study prepared by Ciba-Geigy Corp. 60 p.

Photodegradation-soil 43159327 Atkins, R. (1994) Soil Surface Photolysis of Phenyl (carbon 14) CGA-152005 in Natural Sunlight: Lab Project Number: 573: 70-91. Unpublished study prepared by PTRL East, Inc. 87 p.
43159328 Atkins, R. (1994) Soil Surface Photolysis of Triazine (carbon 14) CGA-152005 in Natural Sunlight: Lab Project Number: 574: 67-91. Unpublished study prepared by PTRL East, Inc. 88 p.

Aerobic soil metabolism 42685250 Atkins, R. (1993) Aerobic Metabolism of (C arbon 14)Triazine CGA-152005 in Sandy Loam Soil: Lab Project Number: 585: 88-91. Unpublished study prepared by PTRL East, Inc. 156 p.
42685251 Atkins, R. (1993) Aerobic Metabolism of (carbon 14)Phenyl-CGA-152005 in Sandy Loam Soil: Lab Project Number: 583: 86-91. Unpublished study prepared by PTRL East, Inc. 175 p.
43387712 Atkins, R. (1994) Aerobic Metabolism of Triazine-(Carbon 14)-CGA-152005 in Soil at Approximately pH 6: Lab Project Number: 636: 158-91. Unpublished study prepared by PTRL East, Inc. 212 p.
43387713 Atkins, R. (1994) Aerobic Metabolism of Phenyl-(Carbon 14)-CGA-152005 in Soil at Approximately pH 6: Lab Project Number: 635: 157-91. Unpublished study prepared by PTRL East, Inc. 225 p.

Anaerobic soil metabolism 42685252 Atkins, R. (1993) Anaerobic Metabolism of ( carbon 14)Triazine-CGA-152005 in Sandy Loam Soil: Lab Project Number: 586: 87-91. Unpublished study prepared by PTRL East, Inc. 103 p.
42685253 Atkins, R. (1993) Anaerobic Metabolism of ( carbon 14)Phenyl-CGA-152005 in Sandy Loam Soil: Lab Project Number: 584: 85-91. Unpublished study prepared by PTRL East, Inc. 103 p.
43387714 Atkins, R. (1994) Anaerobic Metabolism of Triazine-(Carbon 14)-CGA-152005 in Soil at Approximately pH 6: Lab Project Number: 638: 155-91. Unpublished study prepared by PTRL East, Inc. 128 p.
43387715 Atkins, R. (1994) Anaerobic Metabolism of Phenyl-(Carbon 14)-CGA-152005 in Soil at Approximately44 pH 6: Lab Project Number: 637: 156-91. Unpublished study prepared by PTRL East, Inc. 157 p.

Anaerobic aquatic metab. 43387716 Atkins, R. (1994) Anaerobic Aquatic Metabolism of Triazine-(Carbon 14)-CGA-152005: Lab Project Number: 640: 163-91. Unpublished study prepared by PTRL East, Inc. 351 p.
43387717 Atkins, R. (1994) Anaerobic Aquatic Metabolism of Phenyl-(Carbon 14)-CGA-152005: Lab Project Number: 625: 162-91. Unpublished study prepared by PTRL East, Inc. 352 p.

Aerobic aquatic metab. 43387718 Atkins, R. (1994) Aerobic Aquatic Metabolism of Triazine-(Carbon 14)-CGA-152005: Lab Project Number: 639: 160-91. Unpublished study prepared by PTRL East, Inc. 161 p.
43387719 Atkins, R. (1994) Aerobic Aquatic Metabolism of Phenyl-(Carbon 14)-CGA-152005: Lab Project Number: 624: 161-91. Unpublished study prepared by PTRL East, Inc. 150 p.

Leach/adsorp/desorption 42685254 Kesterson, A. (1992 ) Column Leaching of (carbon 14)Triazin e-CGA-152005 in Four Soil Types: Lab Project Number: 533: 7-91. Unpublished study prepared by PTRL East, Inc. 194 p.
42685255 Atkins, R. (1993) Column Leaching of (carbon 14)Triazine-CGA-152005 in Four Soil Types following 30 Days of Aerobic Aging: Lab Project Number: 534: 8-91. Unpublished study prepared by PTRL East, Inc. 215 p.
42685256 Atkins, R. (1993) Column Leaching of (Carbon 14)Phenyl CGA-152005 in Four Soil Types Following 30 Days of Aerobic Aging: Lab Project Number: 535: 9-91. Unpublished study prepared by PTRL East, Inc. 214 p.
42685257 Kesterson, A. (1992) Soil Adsorption/Desorption of Triazine Labelled (Carbon 14) CGA-152005 by the Batch Equilibrium Method: Lab Proj ect Number: 531: 6-91. Unpublished study prepared by PTRL East, Inc. 69 p.
43159329 Kesterson, A. (1993) Soil Adsorption/Desorption of (carbon 14) CGA-159902 by the Batch Equilibrium Method: Lab Project Number: 532: 10-91. Unpublished study prepared by PTRL East, Inc. 60 p.
43159330 Atkins, R. (1993) Soil Adsorption/Desorption of Phenyl-(carbon 14)-CGA-300406 by the Batch Equilibrium Method: Lab Project Number: 702: 114-92 . Unpublished study prepared by PTRL East, Inc. 78 p.
43387720 Nixon, W. (1994) Soil Adsorption/Desorptio n of (Carbon 14)-G-28533 by the Batch Equilibrium Method: CGA-152005: Lab Project Number: 816: 326-93. Unpublished study prepared by PTRL East, Inc. 76 p.

Terrestrial field dissipation 43159331 Rice, F.; Wiepke, T. (1994) Dissipation of CGA-152005 in Soil under Field Conditions with and without Corn in Iowa: Final Report: Lab Project Number: 40198: CIGNC01G-2: 85-92. Unpublished study prepared by ABC Laboratories, Inc.; ALTA Analytical Laboratory, Inc. 420 p.
43159332 Rice, F.; Wiepke, T. (1993) Dissipation of CGA-152005 in Soil under Field Conditions with and without Corn in Georgia: Final Report: Lab Project Number: 40199: CG-9202: 86-92. Unpublished study prepared by ABC Laboratories, Inc.; Enseco-Cal Lab. 277 p.
43387721 Rice, F.; Wiepke, T. (1994) Dissipation of CGA-152005 in Soil Under Field Conditions with and without Corn in Iowa: Amendment Number 1 to Final Report: Lab Project Number: 40198A: 85-92. Unpublished study prepared by ABC Labs, Inc. and ALTA Analytical Labs, Inc. 111 p.45 43387722 Rice, F.; Wiepke, T. (1994) Dissipation of CGA-152005 in Soil Under Field Conditions with and without Corn in Georgia: Amendment No. 1 to Final Report: Lab Project Number: 40199A:: 86-92. Unpublished study prepared by ABC Labs, Inc. and Enseco-CAL Lab. 81 p.
43387724 Coody, P. (1994) Soil Dissipation of (Carbon 14)-CGA-152005 Under Actual Field Conditions in Kentucky: Lab Project Number: 696: 95-92. Unpublished study prepared by Ciba Plant Protection and PTRL East, Inc. 474 p.
43387725 Coody, P. (1994) Soil Dissipation of (Carbon 14)-CGA-152005 Under Actual Field Conditions in North Carolina: Lab Project Number: 715. Unpublished study prepared by PTRL East, Inc. 425 p.
44449202 Wiepke, T.; Judy, D.; Irrig, H. (1997) Final Report: Dissipation of Peak (Prosulfuron) on Soil Under Field Conditions with and without Winter Wheat in Kansas: Lab Project Number: 21-96: 43065. Unpublished study prepared by ABC Laboratories, Inc., and Novartis Crop Protection, Inc. 468 p.
44449203 Purdy, J. (1995) Soil Dissipation Study at Three Trial Sites with CGA 152005 75WG: (Final Report): Lab Project Number: CER 01007/93: E3-06-065: 644-97. Unpublished study prepared by Envirotest Labs., and Novartis Crop Protection, Inc. 109 p.
44538301 Wiepke, T. (1998) Final Report Amendment No.1: Dissipation of Peak (Prosulfuron) in Soil Under Field Conditions with and without Winter Wheat in Kansas: Lab Project Number: 21-96: 43065: 168002. Unpublished study prepared by ABC Labs., Inc. and Novartis Crop Protection, Inc. 32 p.

Non-Guideline Study 42974700 Ciba-Geigy Corp. (1993) Submission of Ecological Effects Data in Response to EPA Request for Data in Support of Experimental Use Permit for CGA-152005 Herbicide (Exceed) on Corn. Transmittal of 1 Study.

9.2. Open-literature Citations

Battaglin, W.A., Furlong, E.T., Burkhardt, M.R., and Peter, C.J., 1999, Occurrence of sulfonylurea, imidazolinone, and ot her herbicides in Midweste rn rivers, reservoirs, and ground water, 1998, in Morganwalp, D.W., a nd Buxton, H.T., eds., U.S. Geological Survey Toxic Substances Hydrology Program --Proceedings of the Technical Meeting, Charleston, South Carolina, March 8- 12, 1999--Volume 2 of 3--Contamination of Hydrologic Systems and Related Ecosystems: U.S. Geological Survey Water-Resources Investigations Report 99-40 18B, p.2 15-226.

Battaglin, W.A., Furlong, E.T., Burkhardt, M.R., and Peter, C.J., 2000, Occurrence of sulfonylurea, sulfonamide,imidazolinone, and othe r herbicides in rive rs, reservoirs and ground water in the Midwestern United States, 1998:The Science of the Total Environment, v. 248, no. 2-3, p. 123-133.

Battaglin, W.A., Furlong, E.T., and Burkhard t, M.R. 2001, Concentration of selected sulfonylurea, sulfonamide, and imidazolinone he rbicides, other pesticides, and nutrients in 71 streams, 5 reservoir outflows, and 25 we lls in the midwestern United States, 1998: U.S. Geological Survey Water-Resources Investigations Report 00-4225, 123 p.

Fletcher, J. S., Nellessen, J. E., & Pfleeger, T. G. 1994. Literature review and evaluation of the EPA food-chain (Kenaga) nomogram, an instru ment for estimating pesticide residues on plants. Environmental Toxicology and Chemistry, 13(9), 1383-1391.46 Fletcher, J. S., Pfleeger, T. G., & Ratsch, H. C. 1993. Potential environm ental risks associated with the new sulfonylurea herbicides. Envi ronmental Science and Technology, 27(10), 2250-2252.

Hoerger, F., & Kenaga, E. E. 1972. Pesticide Resi dues on Plants: Correlation of Representative Data as a Basis for Estimation of their Magni tude in the Environment. In F. Coulston & F. Korte (Eds.), Environmental Quality and Safety: Chemistry, Toxicology, and Technology (Vol. 1, pp. 9-28). New York: Academic Press.

SLUA report. Prosulfuron. Screening Level Usag e Analysis. Environmental Protection Agency, Biological and Economic Analys is Division, Office of Pestic ide Programs, United States Environmental Protection Agency. September 1, 2011.

Steinheimer, T.R., Pfeiffer, R.L., Scoggin, K. D., and Battaglin, W.A., 2000, Reconnaissance survey of sulfonamide. sulfonylurea and imidazo linone herbicides in surface streams and groundwater of the Midwestern United Stat es, in Steinheimer, T.R., Ross, L.J., and Spittler, T.D., eds., Agrochemical Fate a nd Movement--Perspective and Scale of Study: American Chemical Society Symposium series 75 1, p. 248-271.

Teske, M. E., & Curbishley, T. B. 2003. AGDISP Version 8.07 User Manual. Prepared For United States Department of Agriculture Fore st Service. C.D.I. Technical Note No. 02- 06. June 2003.

USEPA. 1995. Review of data submitted towards registra tion of the new herbicide prosulfuron and end-products PEAK and EXCEED for uses on corn. DP barcode: D189457, D205396, D205400, D208195, D208196 and D212748. Memo From Akiva D. Abramovitch To Robert J. Taylor and Edwa rd Allen. Environmental Fate and Effects Division. Office of Pesticide Programs, Unite d States Environmental Protection Agency. April 28, 1995.

USEPA. 1998. Guidelines for Ecological Risk Assessment. EPA/630/R-95/002F. United States Environmental Protection Agency (USEPA). Risk Assessment Forum. Office of Research and Development. Available at http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=12460

USEPA. 2003. Registration Eligibility Decisions : Environmental Fate and Ecological Effects Risk Assessment for Chlorsulfuron (DP Barcode: D290034).

USEPA. 2004. Overview of the Ecological Risk Assessm ent Process in the Office of Pesticide Programs . United States Environmental Protec tion Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. Available at http://www.epa.gov/espp/consultation/ecorisk-overview.pdf (Accessed June 19, 2009).

USEPA. 2005. PRZM 3.12.2: Us ers Manual. Online at: http://www.epa.gov/oppefed1/models/water/#przm47 USEPA. 2005. EXAMS 2.98.04.06: Users Manual. Online at: http://www.epa.gov/oppefed1/models/water/#exams

USEPA. 2006. Water models PE Vers ion 5: User Manual. Online at: http://www.epa.gov/oppefed1/models/water/pe5_user_manual.htm

USEPA. 2006. Drinking Water Exposure Assessment for Prosulfu ron Usage on Small Grains and Corn. DP barcode 326831. Memorandum From Mi chael Barrett to Vickie Walters and Jim Tompkins. Environmental Fate a nd Effects Division, Office of Pesticide Programs, United States Environmenta l Protection Agency. November 20, 2006.

USEPA. 2009. Prosulfuron. REVISED Human Health Risk Assessment for the Proposed Establishment of Permanent Tolerances for Uses in/on Cereal Grains (Crop Group 15), Except Rice. Memorandum From Breann Hanson to Christina Swartz and Kathryn Montague. Alternative Risk Integration and Assessment (ARIA) Team Risk Integration Minor Use and Emergency Response Bran ch (RIMUERB) Registration Division. October 20, 2009.

USEPA. 2010. Development and Use of Percent Cropped Ar ea Adjustment Factors in Drinking Water Exposure Assessments. U.S. Environmental Protection Agency, Office of chemical Safety and Pollution Prevention, Office of Pe sticide Programs, Environmental Fate and Effects Division, September 9, 2010. Online at: http://www.epa.gov/oppefed1/models /water/pca_adjustment_dwa.html

USEPA. 2011 BEAD Chemical Profile for Registration Review: Prosulfuron (129031) Memorandum From Sunil Ratnayake, Sepehr Haddad, and Stephen Smearman to Andrea Mojica. Biological and Economic An alysis Division, Office of Pesticide Programs, United States Environmental Pr otection Agency. October 12, 2011.

USFWS/NMFS. 1998. Endangered Species Consu ltation Handbook: Procedures for Conducting Consultation and Conference Ac tivities Under Section 7 of th e Endangered Species Act. Final Draft. United States Fish and Wild life Service (USFWS) and National Marine Fisheries Service (NMFS). Available at: http://www.fws.gov/endangered/ consultations/s7hndbk/s7hndbk.htm

Willis, G.H. and L.L. McDowell. 1987. Pesticid e Persistence on Foliage in Reviews of Environmental Contamination and Toxicology. 100:23-73.48 Appendix A. Supplemental Enviro nmental Fate Information

A1. Sorption Coefficients and Mobility

Table A1 summarizes the sorption coefficients measur ed for prosulfuron. Freundlich adsorption coefficients ranged from 0.75 to 2.78 and Freundl ich desorption coefficients ranged from 0.0 to 7.95. It was apparent that the mobility of pr osulfuron and its degrad ates decreased with increasing soil organic matter. Limited data are available to understand th e influence of pH on sorption and thus a full analysis of the influen ce of various soil/sediment constituents cannot be fully understood.

Table A1. Summary of measured sorption coe fficients for prosulfu ron degradates at 25 o C.

Soil, % OC pH K F ads (L/kg-soil) a K F des (L/kg-soil) b K OC (L/kg-OC) c n ads /n des d

Prosulfuron (MRID:42685257) Loamy sand, 0.42% pH 7.7 0.074 1.15 17.60 1.22/1.14

Sandy Loam, 1.79% pH 7.8 0.273 1.78 15.3 1.17/1.02

Silt Loam 1.58% pH 6.5 0.293 7.95 18.6 1.16/0.80

Silty Clay Loam 0.61% pH 6.5 0.252 2.37 41.3 1.16/1.27

CGA-159902 (MRID: 43159329) Loamy Sand 0.42% pH 7.7 0.400 3.10 95.4 1.08/0.96

Sandy Loam 1.79% pH 7.8 1.24 4.95 69.5 1.20/1.10

Silt Loam 1.58% pH 6.5 0.765 4.71 48.4 1.24/1.09

Silty Clay Loam 0.61% pH 6.9 0.587 2.97 96.2 1.06/1.09

CGA-150829 (MRID: 41656209) e

Sand 0.230 1.07 78 1.15/1.03

Sandy Loam 2.78 1.41 163 0.98/1.12

Silt Loam Soil 0.96 1.84 64 1.18/1.1449 Soil, % OC pH K F ads (L/kg-soil) a K F des (L/kg-soil) b K OC (L/kg-OC) c n ads /n des d

Silty Clay Loam 1.2 2.96 200 1.22/1.08

CGA-300406 (MRID: 43159330) Loamy Sand 0.42% pH 6.5 0.53 6.05 126 0.81/0.76

Sandy Loam 1.00% pH 6.8 0.490 2.80 49 1.15/0.96

Loam 1.11% pH 6.7 0.470 3.60 43 1.13/0.89

Silty Clay Loam 2.59 % pH 6.4 1.27 4.30 49 1.07/1.00

G-28533 (MRID: 43387720) Sandy Loam 1.00% pH 6.8 0.124 0.00 12.4 1.02/-0.013

Loam 0.42% pH 6.7 0.076 0.597 18.1 0.959/1.09

Sand 1.11% pH 6.5 0.208 0.554 18.7 0.984/1.11

Silty Clay Loam 1.67 % pH 6.8 0.273 1.27 16.3 0.991/1.08

a K F ads -Freundlich adsorption coefficient (K d )
b K F des -Freundlich desorption coefficient

c K OC = regressed K d *100/% OC
d n=1/slope of the adsoption or desorption of linear regression of Freundlich equation x/m=(1/n)(lnCe) + ln K d

e DER and study cannot be located therefore the percent of organic carbon and pH were not found.

Both the batch equilibrium adsorption/desorption studies and the soil column leaching studies suggest that parent pros ulfuron somewhat irreversibly adsorb s to soils (that is, once sorbed it does not desorb readily). However, both Freund lich sorption constants fo r parent prosulfuron (less than 1.0 in each of four different soils) , and the appearance of high amounts of prosulfuron in leachates in soil column leaching studies wi th unaged prosulfuron, indicate high potential for leaching of prosulfuron and its degradates to groundwater.

Table A2. Summary of Storage Stability Studies
Parameter Value(s) and Units Source Comments Storage Stability Prosulfuron and its degradates have been shown to be relatively stable in frozen soil after storage for a year at -20 °C 43387726 None50 Parameter Value(s) and Units Source Comments Prosulfuron and its degradates were shown to be stable in water during frozen storage for up to 422 days. Concentrations of parent compound remained unchanged. 43387724 None

No evidence of degradation for prosulfuron or its de gradates in frozen conditions after 342 days. 43387727 None

Table A3. Structures of Prosulfuron and It s Environmental Transformation Products.
Code Name/ Synonym/
Chemical Name/ Formula/MW/ SMILES Chemical Structure

Prosulfuron, CGA-152005
IUPAC: 1-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-3-[2- (3,3,3-trifluoropropyl)phenylsulfonyl]urea

CAS: N-[[(4-methoxy-6-methyl-1,3,5-triazin-2- yl)amino]carbonyl]-2-(3,3,3-trifluoropropyl)- benzenesulfonamide

CAS No.: 094125-34-5

Formula: C 15 H 16 F 3 N 5 O 4 S MW: 419.38 SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O) N(C(=O)N(C 2=NC(=NC(=N2)OC([H])([H])[H])C)[H])[H]

CGA-159902 IUPAC: 2-(3,3,3-trifluoropropyl)phenyl sulfonamide CAS: 2-(3,3,3-trifluoropropyl)-benzenesulfonamide

CAS No.: Formula: C 9 H 10 F 3 N 1 O 2 S 1 MW: 253.24 SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O) N([H])[H]

CGA-150829

IUPAC: 4-methoxy-6-methyl-1,3,5-triazin-2-amine Formula: C 5 H 8 N 4 O 1 MW: 140.15

SMILES: N(C1=NC(=NC(=N1)C)OC)([H])[H]51 Code Name/ Synonym/
Chemical Name/ Formula/MW/ SMILES Chemical Structure

CGA-300406

IUPAC: N-[[(4-hydroxy-6-methyl-1,3,5-triazin-2- yl)amino]carbonyl]-2-(3,3,3-trifluoropropyl)- benzenesulfonamide CAS: N-[[(1,4-dihydro-6-methyl-4-oxo-1,3,5-triazin-2- yl)amino]carbonyl]-2-(3,3,3- trifluoropropyl)benzenesulfonamide] Other: O-desmethyl triasulfuron Formula: C 14 H 14 F 3 N 5 O 4 S 1 MW: 405.35

SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O) N(C(=O)N(C 2=NC(=NC(=N2)C)O[H])[H])[H]

CGA-325025

CAS : N-[[(4-amino-6-methyl-1,3,5-triazin-2-yl)- amino]carbonyl]-2-(3,3,3-trifluoropropyl)- benzenefulfonamide Other: Desmethoxyamino CGA-152005 Formula: C 14 H 15 F 3 N 6 O 3 S 1 MW: 404.37 SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O) NC(=O)NC2= NC(=NC(=N2)N([H])[H])C

CGA-325028

CAS: N- [[[[(aminocarbonyl)amino]carbonyl]amino]carbonyl-2- (3,3,3-trifluoropropyl)

Formula: C 12 H 13 F 3 N 4 O 5 S 1 MW: 382.32
SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O)N( C(=O)N(C( =O)N(C(=O)N([H])[H])[H])[H])[H]

CGA-325026
CAS: N-[[aminocarbonyl)amino]carbonyl]-2-(3,3,3- trifluoropropyl)52 Code Name/ Synonym/
Chemical Name/ Formula/MW/ SMILES Chemical Structure

Formula: C 11 H 12 F 3 N 3 O 4 S 1 MW: 339.29
SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O)N( C(=O)N(C( =O)N([H])[H])[H])[H]

CGA-325027
CAS: N-(aminocarbonyl)-2-(3,3,3-trifluoropropyl)
MW: 296.27
Formula: C 10 H 11 F 3 N 2 O 3 S 1

SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O)N( C(=O)N([H ])[H])[H]

G-28533

CAS: 6-methyl-1,3,5-triazine-2,4(1H,3H)-dione

MW: 127.10 Formula: C 4 H 5 N 3 O 2 SMILES: C1(=NC(=NC(=N1)C)O[H])O[H] MOL FOR:53 Code Name/ Synonym/
Chemical Name/ Formula/MW/ SMILES Chemical Structure

NANC-CGA-159902 CAS: N-[[aminocarbonyl)ami no]carbonyl]-N -acetyl-2- (3,3,3-trifluoropropyl) MW: 338.30 Formula: C 12 H 13 F 3 N 2 O 4 S 1 SMILES: C1=CC=CC(=C1CC(F)(F)F)S (=O)(=O)N(C(N(C(=O)N([ H])[H])[H])=O)C(=O)C

CGA-188838 CAS: 4-amino-6-methyl-1,3,5-triazin-2(1H)-one MW: 126.12 Formula: C 4 H 6 N 4 O 1 SMILES : N(C1=NC(=NC(=N1)C)O[H])([H])[H]

CGA-325030 CAS: N-[[[[[[[[2-(3,3,3- trifluoropropyl)phenyl]sulfonyl]amino]carbonyl]amino]- carbonyl]amino]car bonyl]acetamide Other: Polyimide Acetate MW: 424.35 Formula: C 14 H 15 F 3 N 4 O 6 S 1 SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O)N( C(=O)N(C( =O)N(C(=O)N(C(C)=O)[H])[H])[H])[H]

CGA-273437 CAS: N-[[[4-hydroxymethoxymethyl)-6-methoxy-1,3,5- triazin-2-yl)amino]carbonyl]-2-(3,3,3-trifluoropropyl) MW: 435.38 Formula: C 15 H 16 F 3 N 5 O 5 S 1

SMILES: C(F)(F)(F)CCC1=C(C=CC=C1 )S(=O)(=O) N(C(=O)N(C 2=NC(=NC(=N2)C(O[H])([H])[H])OC)[H])[H]

MW =molecular weight.54 Table A4. Summary of Maximum Amount of Tr ansformation Products Observed in Fate Laboratory Studies.
Transformation Product Study Type MRID Maximum %AR (day) Final %AR (study length)

CGA-150829 Hydrolysis 42685246 (triazine) 46.1 (30, pH 5, 25 o C) 0.8 (15, pH 7, 25 o C) 0.5 (30, pH 9, 25 o C) 46.1 (30, pH 5, 25 o C) 0.7 (30, pH 7, 25 o C) 0.5 (30, pH 9, 25 o C)
Photodegradation in water 42685248 (triazine) 0.7 (30, pH 9, 25 o C, dark) 2.5 (30, pH 9, 25 o C, irradiated) 0.7 (30, pH 9, 25 o C, dark) 2.5 (30, pH 9, 25 o C, irradiated)

Photodegradation in soil 43159328 (triazine) 4.4 (30, pH 7.2, 23.5 o C, dark) 5.2 (30, pH 7.2, 23.2 o C, irradiated) 4.4 (30, pH 7.2, 23.5 o C, dark) 5.2 (30, pH 7.2, 23.2 o C, irradiated)

Aerobic soil 42685250 (triazine) 11.9 (366) 11.9 (366)

43387712 (triazine) 31.0 (366) 31.0 (366)

Anaerobic soil 42685252 (triazine) 8.3 (90) 8.3 (90)

43387714 (triazine) 8.6 (60) 4.7 (90)
Anaerobic Aquatic Metabolism 43387716 (triazine) 37.0 (90) 18.6 (365)
Aerobic Aquatic Metabolism 43387718 (triazine) 9.0 (30) 9.0 (30)

CGA-159902 Hydrolysis 42685247 (phenyl) 64.4 (24 days, pH 5, 25 o C) 0.9 (30 days, pH 7, 25 o C) 1.3 (24 days, pH 9, 25 o C) 58.5 (30 days, pH 5, 25 o C) 0.9 (30 days, pH 7, 25 o C) 0.8 (30 days, pH 9, 25 o C)
Photodegradation in water 42685249 (phenyl) 1.5 (30, pH 9, 25 o C, dark) 1.4 (30, pH 9, 25 o C, irradiated) 1.5 (30, pH 9, 25 o C, dark) 1.4 (30, pH 9, 25 o C, irradiated)

Photodegradation in soil 43159327 (phenyl) 4.9 (30, pH 7.2, 23.5 o C, dark) 6.8 (30, pH 7.2, 23.2 o C, irradiated) 4.9 (30, pH 7.2, 23.5 o C, dark) 6.8 (30, pH 7.2, 23.2 o C, irradiated)

Aerobic soil 42685251 (phenyl) 49 (366) 49 (366)

43387713 (phenyl) 47.8 (274) 47.6 (366)

Anaerobic soil 42685253 (phenyl) 22.4 (92) 22.4 (92)

43387715 (phenyl) 7.5 (90) 7.5 (90)

Anaerobic Aquatic Metabolism 43387717 (phenyl) 60.1(91) 58.6 (364)

Aerobic Aquatic Metabolism 43387719 1.3 (30) 1.3 (30)

CGA-188838 Anaerobic Aquatic Metabolism 43387716 (triazine) 9.6 (365) 9.6 (365)55 Transformation Product Study Type MRID Maximum %AR (day) Final %AR (study length)

G-28533 Hydrolysis 42685246 (triazine) 16.6 (30, pH 5, 25 o C) 16.6 (30, pH 5, 25 o C)

Anaerobic Soil 43387714 (triazine) 1.5 (90) 1.5 (90)
Anaerobic Aquatic Metabolism 43387716 (triazine) 24.3 (274) 19.9 (365)

CGA-300406 Hydrolysis 42685246 (triazine) 8.6 (30, pH 5, 25 o C) 0.5 (30, pH 7, 25 o C) 2.6 (30, pH 9, 25 o C) 46.1 (30, pH 5, 25 o C) 0.5 (30, pH 7, 25 o C) 2.6 (30, pH 9, 25 o C)

42685247 (phenyl) 15.4 (7 days, pH 5, 25 o C) 0.4 (24 days, pH 7, 25 o C) 2.3 (30 days, pH 9, 25 o C) 6.8 (30 days, pH 5, 25 o C) 0.2 (30 days, pH 7, 25 o C) 2.3 (30 days, pH 9, 25 o C)

Photodegradation in water 42685248 (triazine) 3.3 (30, pH 9, 25 o C, dark) 2.8 (21, pH 9, 25 o C, irradiated) 3.3 (30, pH 9, 25 o C, dark) 2.6 (30, pH 9, 25 o C, irradiated)

42685249 (phenyl) 3.6 (30, pH 9, 25 o C, dark) 3.3 (30, pH 9, 25 o C, irradiated) 3.6 (30, pH 9, 25 o C, dark) 3.3 (30, pH 9, 25 o C, irradiated)

Photodegradation in soil 43159328 (triazine) 2.6 (30, pH 7.2, 23.5 o C, dark) 4.1 (30, pH 7.2, 23.2 o C, irradiated) 2.6 (30, pH 7.2, 23.5 o C, dark) 4.1 (30, pH 7.2, 23.2 o C, irradiated)

43159327 (phenyl) 4.1 (30, pH 7.2, 23.5 o C, dark) 4.9 (30, pH 7.2, 23.2 o C, irradiated) 4.1 (30, pH 7.2, 23.5 o C, dark) 4.9 (30, pH 7.2, 23.2 o C, irradiated)

Anaerobic Soil 43387714 (triazine) 4.6 (90) 4.6 (90)

42685252 (triazine) 9.1 (90) 9.1 (90)

42685253 (phenyl) 8.3 (92) 8.3 (92)

43387715 (phenyl) 4.1 (90) 4.1 (90)

Aerobic soil 43387713 (phenyl) 6.2 (184) 5.0 (366)

43387712 (triazine) 6.0 (180) 3.8 (364)

42685251 (phenyl) 7.1 (184) 2.7 (366)

42685250 (triazine) 10.4 (90) 3.2 (366)

Anaerobic Aquatic Metabolism 43387717 (phenyl) 14.6 (14) undetected (364)

43387716 (triazine) 15.5 (14) undetected (364)

Aerobic Aquatic Metabolism 43387718 (triazine) 2.6 (20) 1.9 (30)

43387719 (phenyl) 3.0 (30) 3.0 (30)
43387712 5.8 (60) undetected (366)56 Transformation Product Study Type MRID Maximum %AR (day) Final %AR (study length)

CGA-325025 Aerobic soil (triazine)
42685250 (triazine) 21.6 (366) 21.6 (366)

43387713 (phenyl) 12.5 (122) 0.6 (366)

Anaerobic soil 42685252 (triazine) 25.3 (90) 25.3 (90)

43387714 (triazine) 10 (90) 10(90)

43387715 (phenyl) 18.3 (90) 18.3 (90)

Aerobic Aquatic Metabolism 43387718 (triazine) 9.6 (20) 7.8 (30)

Aerobic Aquatic Metabolism 43387719 (phenyl) 8.5 (30) 8.5 (30)

CGA-325030 Hydrolysis 42685246 (triazine) 22.2 (30, pH 5, 25 o C) 22.2 (30, pH 5, 25 o C)

42685247 (phenyl) 41.1 (30days, pH 5, 25 o C) 41.1 (30 days, pH 5, 25 o C)

Anaerobic Aquatic Metabolism 43387717 (phenyl) 13.4(60) undetected (364)

43387716 (triazine) 15.6 (30) undetected (364)

CGA-325028 Aerobic soil 43387712 (triazine) 2.6 (366) 2.6 (366)

43387713 (phenyl) 1.9 (366) 1.9 (366)
Anaerobic Aquatic Metabolism 43387717 (phenyl) 27.8 (364) 27.8 (364)
Anaerobic Aquatic Metabolism 43387716 (triazine) 26.9 (273) 24.7 (365)

CGA-325026 Anaerobic Aquatic Metabolism 43387717 (phenyl) 4.9 (273) 4.5 (364)

CGA-325027 Aerobic soil 43387713 (phenyl) 2.5 (366) 2.5 (366)

Anaerobic soil 43387715 (phenyl) 1.6 (90) 1.6 (90)

Anaerobic Aquatic Metabolism 43387717 (phenyl) 4.5 (273) 4.1 (364)

NANC-CGA159902 Anaerobic Aquatic Metabolism 43387717 (phenyl) 2.9 (91) 2.0 (364)
Anaerobic Aquatic Metabolism 43387716 (triazine) 3.0 (59) 2.9 (365)
Abbreviations: %AR=percent applied radioacti vity present as the identified compound

Hydrolysis of prosulfuron was found to be pH-dependent (MRIDs: 42685246 and 42685247 for triazine and phenyl label, respectiv ely). At pH 5, hydrolysis was fast er than at pH 7 and 9. At pH 5, prosulfuron degraded with half-lives of 10 days (average of the two ra diolabels; triazine and57 phenyl labels). However at pH 7 and 9, prosulfu ron was relatively stab le during the 30 day study period and no major degradates were identified. Figure A5 shows the hydrolysis pathway of prosulfuron at pH 5.

Figure A5. Hydrolysis Degradation Pathw ay of Prosulfuron (modified from MRID 42685246 and 42685247), page 1.12 and 2.11, respectively.

At pH 5, the major degradation products are brid ge-cleavage degradates containing a single ring. These degradates are: 2-(3,3,3-trifluor opropyl)benzenesulfonamide (CGA-159902) and 4- methoxy-6-methyl-l,3,5-triazin-2-amine (CGA -150829). Formation of these two degradates increases with time, reaching as high as 45% and 60% of the applied radioactivity for CGA150829 and CGA-159902, respectively, after 30 days . In the triazine-labeled study, another degradate containing an intact triazine ring wa s observed; this degradate was 6-methyl-1,3,5- triazine-2,4(W, 3H)dione (G-28533) and the amount formed increased with time, reaching about 15-16% at 30 days.

In both the triazine- and the phenyl -labeled studies a degradate w ith an open triazine ring was isolated and characterized (IR, 13 C and proton NMR, MS). The struct ure consistent with N-[ ( [ ( [([(2-[3,3,3-trifluoropropyl1phenyl)-sulfonyl ]amino)carbonyl]amino)carbonyl]amino)carbonyl] acetamide (“polyimide acetate” or “CGA-325030”) was assigned to this degradate. Formation of CGA-325030 increased with time, reaching as high as 22% by 30 days. Finally, N-( [(4- hydroxy-6-ethyl-1,3,5-triazin-2- yl)amino]carbonyl)-2(3, 3 ,3 -trifluoropropyl) benzene sulfonamide (“desmethyl prosulfuron”, “d esmethyl CGA-152005”, “CGA-300406”) have been58 identified. The maximum amount of this degradate appeared at 10 days (14% of the applied), and decreased afterwards. Maximum concentrations of prosulfuron and transformation products observed in the studies ar e reported in Table 4. Two photodegradation in water studies were submitted and reviewed (MRIDs: 42685248 and 42685249 for the triazine and phenyl labeled ring, respectively). Both studies are acceptable and satisfied the data requirement. In addition, the registrant submitted supplementary data on the electronic absorption spectra of several degradates in aqueous solutions at pHs 5, 7 and 9 (MRIDs: 42387710 and 42387711). The electronic abso rption spectra of prosulfuron and its major degradates are between 200 and 400 nm wi th no absorption at wavelength above 290 nm. Thus, prosulfuron nor its major degradates are li kely to degrade by dire ct photolysis (in water and in soil). Similarly, the labor atory studies showed that direct photolysis is not an important degradative pathway for prosulfuron. Parent pr osulfuron degraded slow ly (10-15% degradation of the applied) in pH 9 buffer solutions, under bo th irradiated and dark conditions, during the 30- days duration of the study. The de gradates identified were simila r to the hydrolysis products; CGA-150829, CGA-159902 and "desmet hyl prosulfuron” or CGA-30040 6 with percentages that did not exceed 4.0 % of the applied in both irradiat ed and dark samples. More details about the transportation products can be found in Table A4

.
In terms of photodegradation in soils two studies were submitted and found that satisfy the data requirements (MRIDs: 43159327 and 43159328, phenyl a nd triazine labeled, respectively).The studies demonstrated that photode gradation on soil (sandy loam soil of the Huntington series; pH 7.1; 13.0 to 35.3 °C; 37.52 °N, 84.20 °W)

, is not an important degradative pathway for prosulfuron. After 30 days (phenyl label) prosulfuron was recove red ~ 83.7% in the irradiated samples and 89.7% in the dark control samples. Between 16 to 20% parent prosulfuron degraded over the 30-day duration of the study in sunlig ht exposed samples. However, most of the degradation is likely to come from microbial and/or abiotic hydrolysis degradation. The degradates identified in this st udy were CGA-159902 and CGA-300406. CGA-159902 accounted for 6.8 and 4.9% of the applied radioactivity for irradiated and dark samples, whereas CGA-300406 accounted for 4.9 and 4.1% of the app lied, for irradiated and dark samples, respectively (Refer to Table 4) . Two unidentified degradates were detected with maximum radioactivity of 2.7% of the applied radioactivity. The half- lives were estimated to be 130.9 and 260.9 days for the irradiated and dark contro l samples, respectively. The volatiles never exceeded 1.1%.

In the triazine label st udy, after 30 days prosulfuron was r ecovered ~ 93.8 % in the irradiated samples and 93.8% in the dark control samples. The degradates identifie d in this study were CGA-150829 and CGA-300406. CGA-150829 accounted for 5.2 and 4.4% of the applied radioactivity for irradiated and dark samples, whereas CGA-300406 accounted for accounted for 4.1 and 2.6 % of the applied radioa ctivity in irradiated and da rk samples respectively. Three unidentified degradates were de tected in both irradiated a nd dark samples with maximum radioactivity of 2.3% of the applied radioac tivity one of which was identified as CGA-325025. The half-lives were estimated to be 110.5 and 310.7 days for the irradiated and dark control samples, respectively. The volatiles never exce eded 0.4% of the applied radioactivity.

In these studies, between 16 to 20% parent prosulfuron degr aded over the 30-da y duration of the study in sunlight exposed samples. However, most of the degradation is likely to come from microbial and/or abiotic hydrolys is degradation. The results of these studies indicated that59 photolysis would contribute to the environmenta l degradation of prosul furon although it is not anticipated to be a dominant mechanism. The degradation pathway was not provided in the studies.

Four studies have been submitted and found acceptable performed in two different soils for aerobic soil metabolism. The first two studies we re conducted using the Huntington series (sandy loam) with pH of 6.6, 1.17 %OC (MRIDs: 42685250 and 42685251 for triazine- and phenyllabeled studies, respectively). In the triazine study, pr osulfuron degradated with an initial halflife of 152.0 days (calculated from 0 to 123 DAT by the registrant) and se condary half-life of 279.7 (calculated from 123 to 364 DAT by the registra nt). Including all the da ta points (0 to 364 days) the half-life of prosulfuron was 211 da ys. Prosulfuron was 98.6-100.8% of the applied radioactivity immediately af ter treatment, 54.1-60.7% at 4 m onths, 49.1-53.5% at 6 months, 39.2-39.2% at 9 months and 26.7-36.7% at 12 months. Three degradat es were identified in the soils: CGA-150829, CGA-300406 and CGA-325025 with a maximum applied radioactivity of 11.9 %, 10.4% and 21.6% at 12 months, resp ectively. At the end of the study CO 2 totaled 3.1- 3.5% of the applied radioactivity and other volatile s totaled <0.4%.

In the phenyl ring labeled from the Huntington series prosulfur on degraded with an initial registrant-calculated half-life of 69.7 days (regr ession from Day 0-Day 62) and a secondary halflife of 155 days (regression from Day 62-Day 365). In addition, all the data was included in the regression for a half-life of 121.1 days (although some evidence of two compartment model degradation was observed). Prosulfuron wa s 100.6-130.6% of the applied immediately posttreatment, 57.4-58.7% at 2 months, 46.2-49.6% at 3 months, 25.6-30.9% at 9 months and 14.6- 15.1% at 12 months. Trace amounts of a compou nd tentatively identified as CGA-352025 were also isolated. At the end of the study CO 2 totaled 1.4-2.0% of the appl ied radioactivity and other volatiles totaled ≤ 0.1%. The degradates found in this study were CGA-159902 to a maximum of 49% and CGA-300406 with 7.1%. Two unknown p eaks were reported. Peak “A” which comprised up to 14.6% of the applied radioactivit y was determined to consist of to 4 compounds; none present at >6.2% of the applied and the other unknown peak did not generate more than 1.5% of the applied radioactiv ity at the end of the study.

The registrant conducted two new studies with Kickapoo series at pH 6.1, 1.49 %OC (MRIDs: 43387712 and 43387713, triazine- and phenyl-labeled studi es, respectively) in an attempt to elucidate the discrepancy in half-lives from th e Huntington series studies aforementioned. In the triazine labeled study, prosulfur on contained an initial half-life of 112.2 (regression from Day 0- Day 123) and a secondary half-life of 159.7 days (regression from Day 123-Day 364). Using all the data points for the regression the half-life obtained was 138.3 days and showed fair first order fit with some evidence of two-compartm ent model degradation. Prosulfuron was 101.8%- 103.2% of the applied radioactivity immediat ely post treatment, 56.9-61.6% at 3 months, 45.3- 47.9% at 4 months, 20.5-20.4 at 9 months and 16.9-18.4% at 12 mont hs. Five degradates were identified in the soil: CGA-150829 (31%), CGA-300406 (3.8%), CGA-325025 ( ≤ 0.2%), CGA325028 (2.6%) and G-28533 ( ≤ 4.4%). At the end of the study CO 2 totaled 9.6% of the applied and other volatiles totaled <0.2%.

In the phenyl labeled study, th e initial registrant-calculate d half-life of 138.4 days and a secondary half-life of 539.1 days for the parent. The regression with all the data points generated60 a half-life of 154.6 days. Prosulfuron was 97.6-99. 5% of the applied radi oactivity immediately posttreatment, 52.5-59.2% at 4 months, 40.2-40.3% at 6 months, 22.0-24.9% at 9 months and 20.5-21.2% at 12 months. Five degradates were identified in this study: CGA-159902 (47.8%), CGA-300406 (<0.6%), CGA- 325025 (5%), C GA-325027 (2.5%) and CGA-325028 (1.9%). At the end of the study the CO 2 totaled 0.5% of the applied radio activity and other volatiles totaled < 0.2%.

These discrepancies in half-lives can be attributed to the poor us e of first order kinetics (by the registrant) using a “biphasic” first order model. In this analysis, we reported the best fit of the single first order and calculating the 90 th percentile of the mean of the half-lives which resultedin a half-life of 188 days for prosulfuron. However, there was some evidence of twocompartment adsorption resulting in some modest increase in persistence (relative to the first order kinetics model) over the 365-days study period (USEPA 2006). In all aerobic soil metabolism studies the major degradates we re CGA-150829 and CGA-159902, which increased with time and reached above 30% of the applie d after 12 months incubation (See Figure A6 for aerobic degradation pathway). Formation of volatile degradates was negligible.

Figure A6. Aerobic Soil Degradation Pathwa y of Prosulfuron (adapted from MRIDs: 43387713), page 2.25.

The studies submitted for anaerobic soil metabolism for the triazine and phenyl labeled were performed using the Huntington (MRIDs: 42685252 and 42685253, respectively) and Kickapoo (MRIDs: 43387714 and 43387715) series. Sandy loam of the Huntington was used with a pH of 6.6 and 1.17%OC. In the triazine labeled study, prosulfuron degraded with a half-life of 123.4 days that was incubated for 60 days under anae robic conditions (nitroge n gas) following 30 days of incubation under aerobic condi tions. Prosulfuron was 98.6-100% of the applied radioactivity immediately posttreatment, 86.5-88.7% at 30 days , 70.2-73.0% at 61 days and 53.6-67.7% at 90 days. Three degradates were identified in the soil CGA-150829 (8.3%), CGA-300406 (9.1%) and61 CGA-325025 (25.3%). Volatiles totaled ~ 0.4% of the applied radioactivity (0.3% CO 2 and others <0.1%). The phenyl labeled study, prosulfu ron degraded with a half-life of 89.0 days. Prosulfuron was 100.6-130.6% of the applied im mediately posttreatment, 74.8-75.5 at 31 days, 58.7-59.5% at 62 days and 53.5-59.6% at 92 days. Two degradates were identified in the soils: CGA-159902 (22.4%) and CGA-300406 (8.3%). At the end of the study the CO 2 totaled 3.5% and other volatile s totaled <0.4%.

Similarly, sandy loam of the Kickapoo was used with a pH of 6.1 and 1.49%OC. In the triazine study, prosulfuron degradated with a half -life of 137.9 days. Parent compound was 101.8- 103.2% of the applied immediately after tr eatment, 78.9-82.3% at 30 days, 71.9-73.2% at 60 days and 64.1-64.3% at 90 days. Four degradat es were identified in this study: CGA-150829 with 8.6% of the applied radioactivity at 90 days, CGA-300406 (4.6%), CGA-325025 (10%) and G-28533 with (1.5%). The total amount of volat iles was 0.6% (CO2~ 0.4% and other <0.2%). The studies using the phenyl ring labeled pr osulfuron generated a half-life of 136.8 days. Prosulfuron was 97.9-99.5% of the applied radi oactivity immediately after treatment, 83.2- 85.7% at 30 days, 76.5-77.8 at 59 days and 60.462.4% at 90 days. Four degradates were identified in the soils (applied radioac tivity at 90 days): CGA-159902 (7.5%), CGA300406 (4.1%), CGA-325025 (18.3%) and CGA-325027 ( 1.6%). At the end of the study CO 2 totaled 0.3% and other volatiles totaled 0.1%.

The average of the four soils resulted in a half-life of 121.8 days for the parent compound. Mineralization in these studies was minimal. In addition, samples from these studies were storaged at 4 °C for 18 months for re-analy ses (the 90 days samples) and found that no significant degradation occu rred during storage.

On the other hand, the aerobic a nd anaerobic aquatic metabolism studi es show shorter half-lives than those from the soil metabolism studies indica ting the important role that abiotic hydrolysis plays in the degradation of pr osulfuron as discussed below.

The anaerobic aquatic metabolism studies were conducted using flooded silt loam sediment obtained from a pond in Fayette County, Kentucky; incubated in the dark at 24-26 °C for 12 months (pH 7.0). Radioactivity partitioned pr edominantly into the aqueous phase, but partitioning into the sediment phase increased with time. In the triazine ring labeled study (MRID: 43387716), prosulfuron degraded (in a bipha sic pattern) with an in itial half-life of 13.3 days (regression from 0-30 days), a secondary half-life of 25.8 days (regression from 30-120 days) and a monophasic degradation of 16.4 days (regression from 0-365 days). Prosulfuron was 95.3-98.9% of the applied immediat ely after treatment, 74.1-77.2% at 7 days, 46.6-53.3% at 14 days, 16.4-17.8% at one month, 6.1-9.5% at two months, and between ≤ 2.2% between 3-12 months. Seven degradates were identified prim arily occurring in the water phase (applied radioactivity at 12 months): G-28533 ( 24.3%), CGA-188838 (9.6%), CGA-150829 (18.6%), NANC-CGA-159902 (2.9%), CGA-325028 (26.9%), C GA-300406 (undetected after 4 months), and CGA-325030 ( ≤ 0.2%). At the 12 months treatment, CO 2 totaled 4.4% of the applied and other volatiles totaled <03%. The ratio of total prosulfuron resi dues in the water and sediment was approximately 1:1 at 12 months.62 In the phenyl study, (MRID: 43387717) prosulfuron de graded with an initi al half-life of 20.1 days (regression from 0-30 days), secondary ha lf-life of 20.1 days (regression from 30-120), a monobasic half-life of 17.2 days (regression fr om 0-364 days). Prosulfuron was 96.0-97.3% of the applied immediately post-treatment, 68.4-69.9% at 7 days, 46.0-52.2% at 14 days, 16.4- 20.7% at one month, 5.1-8.6% at two months, and ≤ 1.2% between 3 and 12 months. Seven degradates were identified in the sediment s (applied radioactivity at 364 days): NANC-CGA159902 (<2.9%), CGA-325030 ( ≤ 0.7%), CGA-325028 (27.8%), CGA-325027 (4.5%), CGA325026 (4.9%), CGA-300406 (<0.8%) and CGA-159902 ( 58.6%). At 12 months post-treatment CO 2 totaled <0.1% of the applied and others vola tiles ranged from 0.4 to 3.1%. The ratio of total residues in the water and sediment was approximately 6:1 at 9 and 12 months.

Total prosulfuron was less than 2% of the a pplied by 12 months. Prosulfuron degraded in a biphasic pattern with average half- life of 13.5 days for the primary (90 th percentile 13.9 days) and a secondary half-life of 23.0 days (a 90 th percentile of 31.7 days ). A monophasic degradation calculation produced an averag e half-life of 16.8 days (90 th percentile of 18.0 days). The aforementioned half-lives were calculated by the registrant however, in the last DWA (USEPA 2006), more conservative estimation method was used (treating the two st udies as one) and the half-life reported was 52.5 days (based upon th e 3x mean half-life for two studies using one sediment source). The 90 th percentile upper confidence interval of the mean half -life of the two studies (phenyl- and triazi ne-labeled) prosulfuron applied in separate studies for pond sediment taken from Fayette Co. KY) was 20.1 days (regr ession was done from 0-182 days, after the DT50 was apparent). Therefore, more conservati ve estimation method trea ting these studies as one study (EFED was not sure that this sediment gave typical re sults given the fact that the anaerobic soil metabolism half-lives were significantly longer in a di fferent rest soil/sediment).

The proposed degradation pathway of prosul furon in sediment under anaerobic aquatic conditions is shown in Figure A7. The degradation shown in Figure A7 was a combination of the two radiolabeled studies performed on prosulfuron (MRIDs: 43387717 and 43387716). The degradate NANC-CGA-159902 was first detected in this study and a tentative structure was assigned to it. The registrant has indicated th at they will be conducti ng a batch equilibrium (adsorption/desorption study) with the degr adate tentatively identified as NANC-159902 once this chemical species is synthe sized and fully characterized, howe ver, no more studies for this chemical has been submitted. No more studies have been submitted regarding this degradate. Refer to Table A4 for more information about transformation products.63 Figure A7. Anaerobic Aquatic Metabolism Degr adation Pathway of Prosulfuron (adapted from MRIDs: 43387717 (phenyl label) and 43387716 (triazine label), page 6.27 and 5.26, respectively).

The aerobic aquatic metabolism studies were co nducted using phenyl a nd triazine labeled prosulfuron (MRIDs: 43387718 and 43387719, respect ively). Although prosulfuron is not intended for aquatic uses, the registrant conduc ted these studies in support of the petitioned terrestrial use. Parent prosulfu ron applied to loam/water sedi ment (pH 6.5-7.7) declined from 100% to 69-83% of the applied ra dioactivity after 30 day incubati on in the flooded system. Total radioactivity partitioned predominan tly into the water phase. The half-lives found in the studies were 59.5 and 68.4 days for triazine and phenyl la bels, respectively. The average half-life was 64 days and the 90 th percentile was 77.6 days. However, it is uncertain if first order kinetics it’s a good fit for the data since appeared that studies have a short duration time with few samples that resulted to accurately calculate persistence for subset time periods. A more conservative value was reported in the last DWA (U SEPA, 2006) that both studies we re treated as one study (halflife= 3x the half-life value). Three degradates were identified in the studies were CGA-300406, CGA-150829 and CGA-159902 but none of th em were major degradates ( Refer to Table A4 ).

All of the column leaching studies submitted ar e acceptable. In the unaged study, greater than 86% of the radioactivity was found in the leachate as parent prosul furon, except in the silty clay loam column (54%). However, when prosulfuro n was aged aerobically for 30-days with the incubated soil placed on top of the columns a signi ficant reduction in the am ount of radioactivity64 (in terms of parent prosulfuron) was recovered in the leachates. This reduction was observed for both the triazine (MRID:42685255) and the phenyl (MRID:42685256) labeled aged prosulfuron.

Moreover, a significant increase in parent prosulfuron was observed in the 0 to 6 inches depths in all cases when compared with the amount of pros ulfuron in the same depth in the unaged study. Below the 6 inch depth, parent pr osulfuron was essentially equally distributed in all segments. Although the appearance of parent prosulfur on in the leachates d ecreased upon aging, the amount of parent prosulfuron present in the l eachates was still significant (34 to 57%). The bridge-cleavage degradates CGA-159902 and CGA- 150829 were also present in the leachates (maximum of 3.35% CGA-159902 in the loamy sand column with CGA-300406 less than 2% of the applied radioactivity).

The batch equilibrium adsorption/desorption studies were performed with the parent(prosulfuron, MRID: 42685257) and some degradates: CGA-159902, CGA-150829, CGA300406 and G-28533 (MRIDs: 43159329, 41656209, 43159330 and 43387720, respectively). Four soils coming from Fayette County were util ized. The texture, soil characteristics and soils series names are included in the appendix. The adsorption/desorption values are summarized on Appendix A1. The adsorption/desorption data in Appendix A1 are expressed in terms of Freundlich sorption constants.

In all the four studies parent prosulfuron a nd its degradates adsorbed weakly. However, desorption data suggest that adsorption may be ir reversible and that, once adsorbed, the tendency to desorbs may decrease.

For prosulfuron, the amount adsorbed ranged be tween 3.8 and 21.5% and the percent desorbed ranged between 7.6 and 46.5% of the amount that ha d been adsorbed. The adsorption/desorption coefficients (K d values) for triazine labeled were de termined to be 0.074/1.146 for loamy sand, 0.273/1.777 for sandy loam, 0.293/7.953 for silt loam and 0.2519/2.377 for silty clay loam. The organic carbon adsorption/deso rption coefficients (Koc valu es) were determined to be 17.60/272.79 for loamy sand, 15.25/99.25 for sandy loam, 18.56/503.34 for silt loam and 41.30/389.62 for silty clay loam.

Based on the use of K oc values to predict leaching potential where K oc values greater than 5,000 denote immobility of a chemical in soil and K oc values between 0 to 50 denote mobility in soil, prosulfuron is predicted to have mobility in each of the four soil types. This mobility was also evident with the degr adates studied.

The degradate G-28533 adsorbed weakly and desorbed readily (reversible adsorption/desorption). However, irreversibility between adsorption/desorption was also noted with the degradates CGA-159902 and CGA-30 0406, although in both cases adsorption was weak. For CGA-300406 irreversible adsorption was noted in the loamy sand soil as well as for CGA-150829. Adsorption and desorption was linear for all degradates except for CGA-300406 in loamy sand soil where n was equal or below 0.8 (n= 1/slope of the linear regression). For more information about the adsorption/desorp tion values for the degradates see Appendix A1. Both the batch equilibrium adsorption/desorption studies and the soil column leaching studies suggest that parent pros ulfuron somewhat irreversibly adsorbs to soils (that is, once adsorbed it65 does not desorbs readily). However, since current adsorption/desorption studies are not designed to study the kinetics of adsorption/desorption, th ere is no information or, the rate at which prosulfuron adsorbs to (or desorbs from) soils. Additionally, Freundlich adsorption constants for parent prosulfuron (all below 1 in four different soils) and th e appearance of high amounts of prosulfuron in leachates in soil column leaching studies with unaged prosulfuron indicates a high potential for leaching for prosulfuron. However, the Freundlich desorption constants are much higher than the corresponding adso rption constants, suggesting that adsorption/desorption is not a reversible process (MRID: 42685257). Finally, the mobility of the prosulfuron and CGA159902 decreased with increasing soil organic matter content.

Four studies were conducted for terrestrial field dissipati on. Two of the studies were 14 C-labelled studies conducted in Kent ucky (MRID: 43387724) and in No rth Carolina (MRID: 43387725). The other two studies were "col d" studies conducted with and w ithout corn crop; one of the studies was conducted in Iowa (MRIDs: 43159331 and 43387721) and the other in Georgia (MRIDs: 43159332 and 4338772).

In the studies, residues were primarily concentr ated in the 0 to 6 inch depth, with sporadic movement to the 6 to 12 inches. No residues were detected below 12 inches in any of the sites at any sampling time. In the Iowa study, the soil used was flager sandy loam pH 5.4 and 1.3%OC. Total prosulfuron residues were sporadically detected in the 6 to 12 inch soil depth at up to 1.1 ppb; prosulfuron residues were not detected (< 0.50 ppb) in soils collected from below the 12 inches depth. The half-life for the monophasic was 10.2 and 19.3 days for the bare ground and corn, respectively (0 to 6 inches ). Biphasic half-lives were 6.2 and 7.8 days for the primary and 31.5 and 43.3 days for the secondary for the bare ground and corn, respect ively. No residues of parent prosulfuron were found in to the 6 to 15 inch depth.

The degradate moving to the 6 to 12 inches depth was CGA-300406 durin g the first to second week. While formation of this degr adate increased in the 0 to 6 in ch depth during the earlier part of the study, it declined to non-de tectable levels after one month; a decline in this degradate usually reflected an increase in the am ount of degradates CGA-159902 and CGA-150829. The degradate CGA-159902 was only detected in the 6-12 inches depth (at 0.6 ppb) at 302 and 358 post-treatment of the bare ground and corn stud ies, respectively and again at 496 day (bare ground). Parent prosulfuron declined from 13 to 7 ppb at day zero to 3 to 4 ppb at 14 days, to 0.86 ppb by 45 days, to undetectab le levels at 358 days.

In the more porous, less acidic, low organic ma tter content of Georgi a site (Fuquay loamy sand series, pH 7.3, 0.52% OC) the movement of parent prosulfuron to the 6 to 12 inches depth was observed in samples collected at 3, 7, 14, 21, and 30 days (corn) at 1, 3, 7, 14, 44 21, 30, 45, 60, 90, and 120 days (bare ground). The half-life for the monophasic was 10.3 and 8.8 days for the bare ground and corn, respectively (0 to 6 inches ). Biphasic half-lives were 4.1 and 4.2 days for the primary and 15.0 and 13.9 days for the secondary for the bare ground and corn, respectively. The degradates CGA-300406, CGA-159902, and CGA- 150829 were predominantly located in the 0 to 6 inches depth. The only movement of de gradates to the 6 to 12 inches depth was with CGA- 300406 at 7 days (corn) and 21 days (bare ground), CGA-159902 and CGA-150829 at 436 days (corn). Parent prosulfur on declined from 13 to 15 ppb by day 45, to undetectable levels by 360 days.66 In addition, two radiolabeled studies were submitted, one of the studies (MRIDs: 43387724; 43387726 (storage stability) was conducted in Kentucky (KY); the other study (MRIDs: 43387725; 43387727 (storage stability) was conducted in North Carolina (NC) for 365 days (See Appendix A2 ).

The soil at the KY site (0-3 inches depth) was characterized as silty clay loam (18% sand, 54% silt, 28% clay, 1.9 % OC and pH 5.68). Considerable radioactivity was detected in the overflow water of the KY study (6.7 to 39%), which was a ssociated with the heavy rainfall events. Prosulfuron and degradates (CGA-159902, CGA-150829, CGA-300406 and NANC-CGA159902) were detected in the overflow water at va rious concentrations during the course of the study. However, most of the radioactivity was confin ed to the 0 to 3 inches top layer, with slow movement to the 3 to 6 inches and only sporadic movement to the 6 to 9 inches depth. This suggests that soil charact eristics coupled with s ite topology and heavy rainfall events following application may lead to run-off. On the other ha nd, there is evidence thatprosulfuron appears to adsorb irreversibly to soils, which may cause pr osulfuron to move off-target with eroded soil particulates prior to degradation.

Total residues recovered in the entire length ( 36 inches) of the soil column treated with phenyl ring labeled prosulfuron were 84.9-101.6% of the applied through 7 DAT, 43.9-73.5% between 15 and 91 DAT and 33.8-49.2% between 182 and 365 DAT. No overflow or surface water was recovered prior to 15 DAT. Residues recovered in the overflow water afte r 15 days ranged from 10.9 to 39% of the applied radioactivity and residu es recovered in the surface water after 15 days

were ≤ 6.86%. At 365 DAT accumulated residues in the column leachates totaled 0.11-0.40% of the applied.

The triazine labeled study result ed in total residues (entire length of th e soil column) of 95.5- 110% of the applied radioactivity through 7 DAT (with the excepti on of one lysimeter collected at 3 DAT); 57.1-72.6% between 15 and 91 days, and 36.4-50.1% at 365 DAT . No overflow or surface water was recovered prior to 15 DAT; the residues recovered in the flow water after 15 DAT ranged from 6.68 to 34.9% of the appl ied radioactivity and residues were ≤ 6.01% of the applied radioactivity. At 365 DAT accumulated resi dues in the column leachates totaled 0% of the applied radioactivity.

Prosulfuron and its degradates we re shown to be stable in wate r during frozen storage conditions. Aliquots of the overflow water from control ly simeters were treated with phenyl label prosulfuron, CGA-300406 and CG A-159902 or with triazine ring labeled prosulfuron and CGA150829. The treated samples were stored frozen (- 20°C) for up to 422 days and then analyzed by HPLC. The relative concentrations in the water remained unchanged during storage.

In the North Carolina study, total radioactivity in the leachates averaged 5.3 ppb or 0.26% of the applied radioactivity in lysime ters remaining in the ground for one year. The half-lives of prosulfuron in the phenyl and triazine studies (reported by the registra nt) were: 5.7 and 7.3 days respectively. The total residues half-lives were 10-10.6 and sec ondary half-lives of 258 and 299 days for the phenyl and the triazine label studi es, respectively. Parentprosulfuron was not detected in the leachates, except in two lysimeters after 13 days. Five degradates were isolated67 from the soil: CGA-300406, CGA-NANC-15990 2, CGA-159906, CGA-150829 (phenyl labeled study only) and CGA-273437 (phe nyl labeled study only).The degradates CGA-159902, CGA150829, CGA-300406 were detected in the leachat e, of which CGA-159902 had the highest detection (2.44 ppb or 0.28% of the dose) by day 63. In the top 0 to 3 inches layer, the degradates CGA-159902, CGA-150829, C GA-300406 and NANC-CGA-159902 togeth er with parent, were detected. The amount of pare nt decreased with time.

Total residues recovered in the entire length ( 36 inches) of the soil column treated with phenyl labeled prosulfuron were 91.5-113% of the applied through 3 DAT; 68.5-77.4% at 14 through 56 DAT and 44.8-57.9% at 278 and 365 DAT. No surf ace water was recovered during the study. At 365 DAT accumulated residues in the column leachates totaled 2.7- 7.5% of the applied. Residues in the leachates consisted of prosulfuron, CGA- 300406, CGA-159902, CGA 325028, NANC-CGA-159902, and three unidentified compounds.

Similarly, total residues recovered in the entire length of the soil column treated with triazine ring-labeled prosulfuron were 84.2-104.7% of the applied radioactivity through 3 DAT, 70.8- 87.7 between 8 and 56 DAT; 58.9-75.0% between 91 and 278 DAT and 53.5-60% at 365 DAT. Surface water was recovered once, at 1.27% of th e applied radioactivity in one sample at 14 DAT. At 365 DAT accumulated residues in the colu mn leachates were composed of prosulfuron CGA-300406, NANC-CGA-159902 and tw o unidentified compounds.

As in the study performed with KY soil, prosulfu ron and its degradates have been shown to be relatively stable in frozen soil in NC with no evidence of degradation of prosulfuron or its degradates during storage (283 days). Figure A8 show the field metabolism pathway for prosulfuron.68 Figure A8: Field Metabolism Pathway fo r CGA-152005, adapted from USEPA, 1995.

The laboratory data suggest that, like most su lfonylurea (SU) herbicides, prosulfuron could be persistent and mobile. Degradation is dependent on pH, with neutral and alkaline media favoring persistence. Photolysis is not an important degradative route fo r prosulfuron. The long aerobic soil metabolism half-lives are in contrast with the much shorter dissipa tion half-lives observed under field conditions. In addition, the shorte r half-lives observed under anaerobic and aerobic aquatic metabolism studies are indi cative of the important role that abiotic hydrolysis plays in the degradation of prosulfuron. Therefore, prosulfuro n would be expected to degrade/dissipate more rapidly in areas where irrigation and/or rainfall is common. On the other hand, in drier areas (particularly in areas of cool weather) prosulfuro n is likely to degrade at a slower rate. Parent prosulfuron and its major degradat es do not bind strongly to soils, but appear to bind irreversibly.

Adsorption appears to increase with time, but no data on adsorption/desorption kinetics are available to support this observation. The low vapor pressure and high water solubility of prosulfuron makes it unlikely for prosulfuron to di ssipate from soil and/or from water by direct volatilization. The major degradates of prosulfuron are those form ed primarily by cleavage of the sulfonylurea bridge, but the desmethyl analogue is also a common degradate. Degradates formed by opening of the triazine ring have been identified in laboratory studies and in the field.

The rate of prosulfuron degrada tion/dissipation would be influenced by the characteristics of the use area, with cold temperature and dry climates increasing the persistence of prosulfuron. The soil characteristic s (well drained versus poorly draine d), the topology of the site and its69 hydrological characteristics are n eeded when evaluating the environmental impact of prosulfuron at specific sites.

The low octanol water partition coefficient of pros ulfuron makes it unlikely to bioaccumulate in fish. The octanol/water partition coefficient de creases with increasing pH and parallels the increase water solubility in going from acidic to alkaline pHs. Although pr osulfuron is relatively stable to abiotic hydrolysis at neutral and alka line pHs, biotic degradation in aqueous media contributes to reduce the amount of prosulfuron available for bioaccumulation. The major degradates of prosulfuron are also very solubl e in water and are not lik ely to bioaccumulate.

Table A4 shows the maximum amount of applied radioactivity observe d for each identified transformation product. Many of the maximums were observed at the final sampling interval with few unknowns and unextracted residues may ha ve been found, so it is likely that some of these maximum percentages would slightly increase. In the diss ipation studies in soil conducted in KY and NC four degradates we re found: CGA-159902, CGA-300406, NAC-CGA-159902 and CGA-150829.70 Appendix B. Summary of available effects studies

Aquatic Organisms

Table B1 contains all available aquatic toxicity endpoints from registrant-submitted studies. The most sensitive endpoints that will be used in qua ntitative risk assessment are highlighted in bold. Below is a brief summary of available aquatic toxicity studies.

Fish

A 96-hour acute toxicity study (MRID 426852-09) was al so carried out with the bluegill sunfish ( Lepomis macrochirus ) at a limit concentration of 155 mg ai/L (mean measured) of prosulfuron technical. No mortality or sublet hal effects were observed in e ither the control or treatment groups resulting in an LC 50 of >155 mg ai/L. Therefore, prosul furon is considered practically nontoxic to bluegill sunfish on an acute exposure basis.

A 96-hour acute toxicity study (MRID 426852-10) was also carried out with the rainbow trout ( Oncorhynchus mykiss ) at a limit concentration of 160 mg ai/L (mean measured) of prosulfuron technical. No mortality or sublet hal effects were observed in e ither the control or treatment groups resulting in an LC 50 of >160 mg ai/L. Therefore, prosul furon is considered practically nontoxic to rainbow trout on an acute exposure basis.

In a 96-hour acute toxicity limit test (MRID 429497-06) with the sheepshead minnow ( Cyprinodon variegatus ), no mortality or sublethal effects resulted from exposure to prosulfuron technical. Since the limit concen tration was 155 mg ai/L, the LC 50 for this study is >155 mg ai/L. Therefore, prosulfuron is consid ered practically non- toxic to the sheepshead minnow on an acute exposure basis.

A 37-day early life-stage toxicity test (M RID 429497-07) was conducted with fathead minnows ( Pimephales promelas ) at mean-measured prosulfuron concentrations of 21.1, 35.8, 58.8, 84.9, and 149.1 mg ai/L. No significant differences we re observed between control and exposure concentrations for any endpoint (survival, hatcha bility, length, wet and dr y weight). Therefore, the NOAEC for the fathead minnow was 149.1 mg ai/L . It should be noted that the test was extended from 36 to 37 days because of a dilu ter control malfunction on day 28 that may have affected test substance concentration valu es during that portio n of the experiment.

Crustaceans

A 48-hour acute toxicity study (MRID 426852-11) was carried out with the freshwater
crustacean Daphnia magna at a limit concentration of 120 mg ai/L. No mortality or sublethal effects were observed in either the contro l or treatment groups resulting in an LC 50 of >120 mg ai/L. Therefore, prosulfuron is c onsidered practica lly non-toxic to D. magna on an acute exposure basis.

A 96-hour acute toxicity study (MRID 432126-01) was conducted with a saltwater mysid species ( Americamysis bahia ) at a limit concentration of 150 mg ai/L. There were seven mortalities as71 well as four individuals exhibiti ng lethargy in the group treated w ith prosulfuron. Since less than 50% mortality was observed in the treatment group, the LC 50 for this study is >150 mg ai/L. Therefore, prosulfuron is consid ered practically non-toxic to A. bahia on an acute exposure basis.

A 21-day chronic toxicity test (MRID 429497-08) was performed with D. magna at mean measured concentrations of 18, 33, 56, 86, and 148 mg ai/L. No statis tically significant difference in any measured endpoint (adult survival, number of young per reproductive day, pooled dry weight per replicate) occurred at any treatment leve l as compared to the control group. Therefore, the NOAEC for this study is the highest concentration tests, i.e. , 148 mg ai/L

Mollusks

In a 96-hour shell deposition study (MRI D 432126-02) with the eastern oyster ( Crassostrea virginica ), no mortality or statistical ly significant effects on shell de position were recorded at the limit concentration of 125 mg ai/L, resulting in an EC 50 of >125 mg ai/L. Therefore, prosulfuron is considered pract ically non-toxic to C. virginica on an acute exposure basis.

Vascular Plants

A 14-day tier II growth and reproduction test (M RID 429497-13) with the aquatic vascular plant species Lemna gibba was performed at mean-measured concentrations of 0.210, 0.407, 0.827, 1.70 and 3.40 μg ai/L of prosulfuron technical. In the three lowest treatment groups, slight stimulation of frond production was observed (6-9%), while at the two highest treatment levels, marked inhibition of frond production of 84% (1.70 μg ai/L) and 97% (3.40 μg ai/L) was reported. The NOAEC and EC50 for this study is 0.83 and 1.22 μg ai/L, respectively.

Nonvascular Plants

A 5-day tier II aquatic nonvascul ar plant toxicity study (MRID 429497-14) was carried out with the green alga Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum ) at prosulfuron mean-measured concentrations of 1.17, 2.78, 4.84, 10.3, and 19.5 μg ai/L. Exposure to concentrations ≥ 4.84 μg ai/L had significant i nhibitory effects on alga; cell density resulting in a NOAEC of 2.78 μg ai/L. The 5-day EC 50 for this study is 10.6 μg ai/L (95% CI: 8.84-12.7 μg ai/L).

Another 5-day tier II aquatic nonvascular plant toxicity stud y (MRID 429497-15) was carried out with the freshwater diatom Navicula pelliculosa at prosulfuron mean-measured concentrations of 6.25, 12.6, 23.0, 46.4, and 83.6 μg ai/L. Exposure to concentrations ≤ 23.0 μg ai/L had a significant stimulatory effect on cell density, while exposure to the two highest concentrations was slight inhibitory (but not statistically significant). Ther efore the NOAEC for this study is 83.6 μg ai/L. The 5-day EC 50 for this study was determined to be greater than the highest concentration tested ( i.e. , >83.6 μg ai/L). It should be noted that variance in the study data was high. At the highest test level ( 83.6 μg ai/L), the mean and standa rd deviation in cell density was 597,750 and 332,000 cells/mL, respectively. At the sec ond highest test level (46.4 μg ai/L), the mean and standard deviation in cell de nsity was 576,000 and 582,000 cells/mL, respectively. Therefore, even large reductions were not statistically discernabl e. Consequently, this study is72 downgraded to supplemental and will not be used quantitatively in risk assessment.

Two tier I aquatic nonvascula r plant toxicity studies (MRIDs 429497-11; 429497-12) were carried out with the cyanobacterium Anabaena flos-aquae and the marine diatom Skeletonema

costatum at limit concentrations of 27.2 and 28.6 μg ai/L, respectively. 5-day cell density was significantly reduced by 22.5% in prosulfuron treated A. flos-aquae cultures as compared to controls, while mean cell density in S. costatum was slightly elevated at the limit concentration as compared to controls. Since less than 50% mortality was observed during both tests, the EC 50 value is greater than the limit concentration.

Table B1. Aquatic Toxicity Profile for Prosulfuron

Species Measured Effect Duration Endpoint Toxicity Value μg ai/L Test Substance % ai MRID (Study Classification)
Freshwater Fish Lepomis macrochirus (Bluegill sunifsh) Mortality 96 hours LC 50 >155,000 †‡ (Practically non-toxic) 99.1% 426852-09 (Acceptable)
Oncorhynchus mykiss (Rainbow trout) Mortality 96 hours LC 50 >160,000 †‡ (Practically non-toxic) 99.1% 426852-10 (Acceptable)

Pimephales promelas (Fathead Minnow) Growth, Survival, Hatchability 37 days NOAEC 149,000* 99.1% 429497-07 (Acceptable)

Freshwater Crustaceans

Daphnia magna

(Water flea) Immobility 48 hours EC 50 >120,000 †‡ (Practically non-toxic) 99.1 426852-11 (Acceptable)

Growth, Survival, Reproduction 21 days NOAEC 148,000* 99.1 429497-08 (Acceptable)

Estuarine/Marine Fish Cyprinodon variegatus (Sheepshead

minnow) Mortality 96 hours LC 50 >155,000 †‡ (Practically non-toxic) 99.1% 429497-06 (Acceptable)

Estuarine/Marine Crustaceans and Mollusks
Americamysis bahia (Mysid shrimp) Mortality 96 hours LC 50 >150,000 †‡ (Practically non-toxic) 99.1% 432126-01 (Supplemental)

Crassostrea

virginica (Eastern oyster) Shell deposition 96 hours EC 50 >125,000 †‡ (Practically non-toxic) 99.1% 432126-02 (Acceptable)
Aquatic Plants Lemna gibba (duckweed) Frond number 14 days EC 50 1.22* 98.7% 429497-13 (Acceptable) NOAEC 0.83* Pseudokirchneriella subcapitata (green algae) Tier II Study Cell density 5 days EC 50 10.6*

98.7% 429497-14 (Acceptable) NOAEC 2.78*73 Species Measured Effect Duration Endpoint Toxicity Value μg ai/L Test Substance % ai MRID (Study Classification) Navicula pelliculosa (freshwater diatom) Tier II Study Cell density 5 days EC 50 >83.6 †
99.1% 429497-15 (Supplemental) NOAEC 83.6

Anabaena flos-aquae (cyanobacterium) Tier I Study Cell density 5 days EC 50 >27.2 †‡

98.7% 429497-11 (Acceptable) NOAEC <27.2 †‡

Skeletonema

costatum (marine diatom)

Tier I Study Cell density 5 days EC 50 >28.6 †‡

98.7% 429497-12 (Acceptable) NOAEC 28.6 †‡

* Bold values represent most se nsitive endpoint and will be used for risk estimation. † Non-definitive study endpoint; cannot be used for risk estimation. ‡ Single concentration limit test.

Terrestrial Organisms

Table B2 contains all available terrestrial toxici ty endpoints from registrant-submitted studies. The most sensitive endpoints that will be used in quantitative risk assessment are highlighted in bold. Below is a brief summary of ava ilable terrestrial toxicity studies.

Birds

A 14-day acute oral toxicity study (MRID 426852-05) with prosulfuron technical was conducted with mallard ducks ( Anas platyrhynchos ) at doses of 100, 215, 464, 1000, and 2150 mg ai/kgbw. Two mortalities occurred in the highest dosage group (2150 mg ai/kg-bw), while five mortalities occurred in the second highest dosage group (1000 mg ai/kg-bw). Since the pattern of mortality was not dose-responsive, an LD 50 value of 1094 mg ai/kg- bw (95% CI: 943-1269 mg ai/kg-bw) was calculated by omitting the highest dosage group. This led to a lower (i.e., more conservative) endpoint value than if the highe st dosage group was us ed in the analysis. Prosulfuron is classified as s lightly toxic to mallard duck on an acute oral exposure basis. Clinical signs of toxicity not ed during the study included lethar gy and stumbling in the 464 mg ai/kg-bw group, lethargy in the 1000 mg ai/kg- bw group, and bloody excreta and lethargy in the highest dosage group (2150 mg ai/ kg-bw). All surviving birds retu rned to normal by test day 4. Reduced feed consumption was noted in the f our highest dosage groups during test days 1 through 3.

A 21-day acute oral toxicity study (MRID 426852-06) with prosulfuron technical was conducted with the bobwhite quail ( Colinus virginianus ) at doses of 1470 and 2150 mg ai/kg-bw. No mortalities occurred in the control or treatmen t groups; therefore the LD 50 was determined to be >2150 mg ai/kg-bw. Prosulfuron is classified as practically nontoxic to bobwhite quail on an acute oral exposure basis. Clinical signs of toxicity noted during the study included ataxa, anorexia, and chalky diarrhea. Based on feed c onsumption data, anorexia was noted in the 1470 mg ai/kg-bw dosage group and slightly reduced feed consumption was noted in the 2150 mg ai/kg-bw group. Out of a random su bset of twelve birds selected for necropsy, one bird at the74 1470 mg ai/kg-bw level had a friable liver. In the 2150 mg ai/kg-bw group, a growth was found attached to the gizzard of one male; one male had friable testis, and one female had resorbed eggs and a reddened enlarged liver.

In an 8-day dietary toxicity study with the mallard duck (MRID 426852-07), dosage levels consisted of 312, 625, 1250, 2500, and 5000 mg ai/kg-diet . No mortality or abnormal behavior was observed in control or treatment groups a nd the dietary LC50 was determined to be >5000 mg ai/kg-diet. Prosulfuron is classified as pr actically nontoxic to ma llard duck on an acute dietary exposure basis.

In an 8-day dietary toxicity study with the bobwhite quail (MRID 426852-08), dosage levels consisted of 312, 625, 1250, 2500, and 5000 mg ai/kg-diet . No mortality or abnormal behavior was observed in control or treatment groups and the dietary LC50 was determined to be >5000 mg ai/kg-diet. Prosulfuron is cl assified as practical ly nontoxic to bobwhite quail on an acute dietary exposure basis.

A chronic reproductive toxicity study (MRID 429497- 01) was carried out with mallard ducks at prosulfuron dietary concentra tions of 28, 100, and 350 mg ai/kg- diet (16 male and 16 female birds per treatment level). Birds were fed a ppropriate treated diet for 22 weeks followed by untreated feed during a three w eek recovery period. There were no treatment-related deaths or adverse behavioral signs recorded at any concentration throughout the study. There was a significant decrease in female body weight compared to control birds during week 22 of the test. There was a significant decrease in the number of eggs laid per hen at 350 mg ai/kg-diet compared to controls. There was a significant de crease in the number of 14-day-old survivors of eggs set at 100 mg ai/kg-bw, and a slight (but non-significant) decrease in hatchling survival at 350 mg ai/kg-diet; effects at both test levels were considered to be treatment-related resulting in a study NOAEC of 28 mg ai/kg-diet. Reduced offs pring survival was attributed to reduced hatching success rather than redu ced hatchling survival rate.

Mammals

A 14-day acute oral toxicity study (MRID 426852-15) wa s performed with Sprague Dawley rats at test substance doses ranging from 400 to 1,000 mg/kg. Clinical signs that were possibly compound related included dose-related increase in staggered gait, lacrimation in females, and hypersensitivity to touch and sound. The LD50 for th is study was 546 mg/kg for female rats, 949 mg/kg for males, and 986 mg/kg for combined sexes.

A 3-month sub-chronic oral toxicity study (MRID 426852-32) was carried out in Sprague Dawley rats at dietary levels of 5, 50, 500, 4,000 and 8,000 mg/kg-diet . In male rats, body weight and body weight gain were reduced by 9 and 13% respectively at the 500 mg/kg-diet level, resulting in a study NOAEL of 50 mg/kg-diet (3.1 mg/kg/day).

In a multi-generation reproduction study (MRID 431593- 19) in rats, treatment groups received dietary concentrations of 10, 200, 2,000, or 4,000 mg/kg-diet of th e test substance. At 2,000 and 4,000 mg/kg-diet, parental mean body weights were significantly lower than controls, resulting in a parental (systemic) toxicity NOAEL of 2 00 mg/kg-diet. In the F1 and F2 offspring, pup75 weights were also reduced at the same test co ncentrations as adults . Thus, the reproductive toxicity NOAEL was al so 200 mg/kg-diet.

Terrestrial Arthropods

A 48-hour acute contact toxicity test (MRID 426852-12) was c onducted with 14-to-21-day-old honeybees at prosulfuron treatment concen trations of 6.25, 12.5, 25, 50 and 100 μg ai/bee. Prepared dosing solutions were applied to the dorsal thorax or abdomen of immobilized bees. Mortality in treatments groups and controls ranged from 0 to 2% a nd all deaths were attributed to handling. No sublethal effects were observed among treated bees. The LD 50 value for honeybees is therefore greater than the highest c oncentration tested (>100 μg ai/bee).

Terrestrial Plants

A 21-day tier II seedling emergence study (MRI D 429747-01) was performed with prosulfuron technical on six species of dico tyledonous plants (soybean, lettu ce, radish, tomato, cucumber, cabbage) and four species of monocotyledonous plants (corn, oa t, ryegrass, onion) at application rates of 0.0025, 0.0050, 0.010, 0.020, and 0.040 lbs ai/A. A continuation study was also carried out at application rates of 0.00001 and 0.0025 lbs ai/A. Percent emergence, percent survival, phytotoxicity, plant height, and plan t dry weight were ev aluated. The most sensitive dicot species endpoint was dry weight for lettuce with corresponding EC 25 and NOAEC values of 7.1 x 10 -5
and 8.0 x 10 -5 lbs ai/A, respectively. The most sens itive monocot species endpoint was plant height for onions with corresponding EC 25 and NOAEC values of 2.6 x 10 -4 and 1.6 x 10 -4 lbs ai/A, respectively.

A 21-day tier II vegetative vigor study (MRI D 429497-10) was performe d with prosulfuron technical on six species of dico tyledonous plants (soybean, lettu ce, radish, tomato, cucumber, cabbage) and four species of monocotyledonous plants (corn, oa t, ryegrass, onion) at application rates of 0.0025, 0.0050, 0.010, 0.020, and 0.040 lbs ai/A. A continuation study was also carried out at applicati on rates of 7.8 x 10 -5 and 0.0025 lbs ai/A. Percent survival, phytotoxicity, plant height, and plant dry weight were measure d. The most sensitive dicot NOAEC was 1.6 x 10 -4 lbs ai/A for soybean dry weight and phytoxic ity index measure. The lowest dicot EC 25 value was 4.6 x 10 -4 lbs ai/A for soybeans. The most sensitive monocot NOAEC was 3.1 x 10 -4 lbs ai/A for onion dry weight and plant height. The lowest monocot EC 25 value was 4.1 x 10 -4 lbs ai/A for onions.

A tier II seed germination phytotoxity test (M RID 429497-09) was carried out with prosulfuron technical on six species of dicotyledonous plan ts (soybean, lettuce, radish, tomato, cucumber, cabbage) and four species of m onocotyledonous plants (corn, oat, ryegrass, onion). The test material was applied at rates of 0.0027, 0.0054, 0.011, 0.022, and 0.043 lbs ai/A and seed germination rates were measured. No significant differences in percent germination existed for any of the test species except for ryegrass, whic h demonstrated an 11% decrease in germination at the highest treatment level. Therefore, the NOAEC for ryegrass is 0.022 lbs ai/A, while the NOAEC for all other plant species is 0.043 lbs ai/A . Since less than 50% inhibition occurred for all plants and treatment groups, th e EC25 is non-definitive and is estimated to be greater than the76 highest concentration tested ( i.e., >0.043 lbs ai/A). It should be noted that the 0.043 lbs ai/A is higher than the current maximum registered use rate of prosulfuron of 0.0356 lbs/A.

Investigations/studies have indicat ed that a small percentage of the label application rate of low dose, high-potency herbicides such as prosulfu ron may impact the repr oduction of non-target terrestrial plants (Asghari and Evans, 1992a, 1992b; Bhatti et al. , 1995; Boutin et al. , 2000; Fletcher et al. , 1993; Fletcher et al. , 1996a, 1996b; Pfleeger et al. , 2011). However, there are no available data on adverse reproductiv e impacts to terrestrial plants from prosulfuron residues due to spray drift.

Table B2. Terrestrial Toxicity Profile for Prosulfuron

Species Measured effect Endpoint Test Duration Toxicity Value (Acute Toxicity Category) Test Substance % ai MRID (Study Classification) Birds

Anas platyrhynchos (mallard duck) Mortality LD 50 14 days 1094 mg ai/kg-bw* (Slightly toxic) 99.2% 426852-05 (Acceptable)
Mortality LC 50 8 days >5000 mg ai/kg-diet † (Practically non-toxic) 99.1% 426852-07 (Acceptable)
Hatching success NOAEC 25 weeks 28 mg ai/kg-diet* 99.2% 429497-02 (Acceptable) Colinus virginianus (Northern Bobwhite

Quail) Mortality LD 50 21 days >2150 mg ai/kg-bw † (Practically non-toxic) 99.1% 426852-06 (Acceptable)

Mortality LC 50 8-days >5000 mg ai/kg-diet † (Practically non-toxic) 99.1% 426852-08 (Acceptable)

Mammals

Rattus norvegicus (laboratory rat) Mortality LD 50 14-days 546 mg/kg-bw* (females) 99.1% 426852-15 (Acceptable: Reviewed by HED) Body weight, body weight gain (subchronic feeding study) NOAEL 3 months 50 mg/kg-diet (males)* (3.1 mg/kg/day) 96% 426852-32 (Acceptable: Reviewed by HED)

Parental weight, F 1 and F 2 pup weights NOAEL 2- generation
test 200 mg/kg-diet (13.3 mg/kg-day; adult males) 99.1% 431593-19 (Acceptable: Reviewed by HED) Terrestrial Arthropods Apis mellifera

(Honeybee) Mortality LD 50 48 hours >100 μg ai/bee 99.1% 426852-12 (Acceptable) Terrestrial Plants
Monocots

(onion) Seedling emergence study: % emergence % survival; phytotoxicity; height; dry weight EC 25

21 days 0.00026 lbs ai/A

99.1% (TGAI) 429747-01 (Supplemental) ‡ Monocots

(onion) NOAEC 0.00016 lbs ai/A

Dicots (lettuce) EC 25 0.000071 lbs ai/A

Dicots (lettuce) NOAEC 0.00008 lbs ai/A

Monocots

(onion) Vegetative vigor study: % survival; EC 25 21 days 0.00041 lbs ai/A 99.1% (TGAI) 429497-10 (Supplemental) ‡77 Species Measured effect Endpoint Test Duration Toxicity Value (Acute Toxicity Category) Test Substance % ai MRID (Study Classification)
Monocots

(onion) phytotoxicity; height; dry weight NOAEC 0.00031 lbs ai/A

Dicots (soybean) EC 25 0.00046 lbs ai/A

Dicots (soybean) NOAEC 0.00016 lbs ai/A

Monocots (multiple species)

Seed germination study: % seed germination EC 25

6 days >0.43 lbs ai/A

99.1% ( TGAI ) 429497-09 (Acceptable) Monocots (ryegrass) NOAEC 0.022 lbs ai/A

Dicots (multiple species) EC 25 >0.43 lbs ai/A

Dicots (multiple species) NOAEC 0.043 lbs ai/A

* Bold values represent most se nsitive endpoint and will be used for risk estimation. † Non-definitive study endpoint; cannot be used for risk estimation. ‡ Tier II plant studies recently do wngraded to “supplemental” because they were not performed with TEP78 Appendix C. Output from OPP Aggregat e Incident Database for Prosulfuron 

# Aggregate Incident Report for EFED

Prosulfuron
PC Code: 129031



### Total Count of Minor Incidents from Aggregated Reports

Minor Fish and Wildlife Incidents (W-B): 0 Minor Plant Incidents (P-B): 37 Minor "Other Nontarget" Incidents (ONT): 0

Date Range Package Seq # Product Sum W-B P-B ONT

11/1/1998 - 009573 052 EXCEED HERBICIDE 1 0 1 0

11/1/1998 - 009573 054 SPIRIT HERBICIDE 2 0 2 0

11/1/1999 - 010837 096 SPIRIT HERBICIDE 12 0 12 0

11/1/1999 - 010837 091 EXCEED HERBICIDE 2 0 2 0

11/1/1999 - 010837 094 PEAK HERBICIDE 2 0 2 0

11/1/2000 - 012499 091 SPIRIT 1 0 1 0

11/1/2001 - 013554 067 SPIRIT 1 0 1 0

11/1/2002 - 014597 057 SPIRIT 2 0 2 0

11/1/2003 - 015713 113 EXCEED 2 0 2 0

11/1/2004 - 016903 054 PEAK CUSTOM PAK 3 0 3 0

11/1/2004 - 016903 057 SPIRIT 2 0 2 0

11/1/2006 - 019130 103 SPIRIT 2 0 2 0

11/1/2007 - 020283 142 PEAK 4 0 4 0

11/1/2009 - 021500 088 SPIRIT 1 0 1 079 Appendix D. STIR Results for Evaluate Potential for Inhalation Risk to Birds and Mammals80 Appendix E. SIP Results for Evaluate Potentia l Risk to Birds and Mammals from Drinking Water Exposure.81 Appendix F. Agency risk quotient (RQ) metric s and levels of concern (LOC) for Federallylisted (listed) threatened/endangered and non-listed species per risk class.

Risk Class Risk Description RQ LOC

Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non-listed animals from acute exposures Peak EEC/LC 50 1 0.5

Acute Restricted Use Potential for effects to animals from acute
exposures Risks may be mitigated through restricted use classification Peak EEC/LC 50 1 0.1

Acute Listed Species Listed species may be potentially affected by acute exposures Peak EEC/LC 50 1 0.05

Chronic Potential for effects to non-listed and listed animals from chronic exposures 60-day EEC/NOEC (fish)

1 21-day EEC/NOEC (invertebrates)

Terrestrial Animals (mammals and birds)

Acute Potential for effects to non-listed animals from acute exposures EEC 2 /LC 50 (Dietary)
0.5
EEC/LD 50 (Dose)

Acute Restricted Use Potential for effects to animals from acute
exposures Risks may be mitigated through restricted use classification EEC 2 /LC 50 (Dietary)

0.2
EEC/LD 50 (Dose)

Acute Listed Species Listed species may be potentially affected by acute exposures EEC 2 /LC 50 (Dietary)
0.1 EEC/LD 50 (Dose)

Chronic Potential for effects to non-listed and listed animals from chronic exposures EEC 2 /NOAEC 1

Plants

Non-Listed Potential for effects to non-target, non-listed plants from exposures EEC/ EC 25 1

Listed Plant Potential for effects to non-target, listed plants from exposures EEC/ NOEC
1 EEC/ EC 0582 Appendix G. Justification for Speci al Study on Plant Reproduction

Guideline Number: Non-guideline Study Titles: Special Study for Non-Ta rget Plant Reproductive Toxicity Rationale for Requiring the Data As stated in the Problem Formula tion, investigations/studies have indicated a small percentage of the label application rate of low dose high potency herbicides such as sulfonylureas (e.g. prosulfuron) may impact the repr oduction of non-target terrestrial plants. However, there are no available data on adverse reproductiv e impacts to terrestrial plants from prosulfuron residues due to spray drift. Terrestrial plant reproductive toxicity data would he lp to screen for potential plant risks associated with prosulfuron use. Plants form the basis of most habitats and contribute significantly to overall environm ental quality. The loss of pl ant reproductive output could potentially have an adverse effect on animals, both invertebrates and ve rtebrates, as many are dependent on plant reproduction for a food source and for habitat quality and structure. A solid understanding of the potential risk s to plants is therefore esse ntial for sound environmental management. A study protocol must be submitted for review and approved by the Agency prior to initiation of the study. Practical Utility of the Data How will the data be used? The data will be used to estimate potential repr oductive risks to non-targ et terrestrial plants, including the likelihood of potential risks to endangered specie s, either by direct effects or by indirect effects, and to redu ce uncertainties associated with the current ecological risk assessment. By refining the assessment, the Agency will be able to determine whether current labeling is appropriate and whether further mitiga tion is necessary. In the absence of this data, risks to terrestrial plants will be presumed.

How could the data impact the Ag ency's future decision-making? These data, once submitted, should allow the Agency to characterize the risk posed to plant reproductive processes from prosulfuron in terrestrial ecosystems. Primary producers (i.e. plants) provide food and habitat vital to ecological processes. Therefore, a solid understanding of the potential risks to non-target plants is essential in order to asse ss the environmental risks the use of prosulfuron may pose. If the data indicate that prosulfuron poses significant risks to these nontarget plant species, the Agency may explore add itional decision options to minimize the risks to these species. The lack of these data will limit th e flexibility the Agency and registrants have in complying with the Endangered Species Act and coul d result in use restrictions for prosulfuron which may otherwise be avoided, or which are unnecessarily severe.