- 2 of 75 **•** Aerobic soil metabolism (OPPTS guideline # 835.4100)

– guideline requirements are partially fulfilled; additional data with supplemental study are needed.

**•** Hydrolysis (OPPTS guideline #835.2120)

– Existing study remains valid, but additi onal hydrolysis data are being requested.

The available ecological effects data are considered in c omplete for the purposes of risk assessment. The following data gaps exist:

**•** Terrestrial p lant r eproduction s tudy (non

- guideline)

**•** Fish acute toxicity test, freshwater (850.1075)

– typical end

- use product

**•** Aquatic invertebrate acute toxicity test, freshwater daphnids (850.1010)

– typical end

- use product

See the attached assessment for a dditional detail s on the current data gaps for environmental fate and ecological eff ect s

.- 3 of 75 

# P roblem Formulation for t h e Environmental Fate and Ecological Risk, Endangered Species, and Drinking

Water Assessments in Support of the Registration Review of Halosulfuron

- methyl

methyl 5

- {[(dimethoxy

- 2

- pyrimidinyl) amino] carbonylaminosulfonyl

- 3

- chloro

- 1

- methyl

- 1

- H

pyrazole

- 4

- carboxylate



### PC Code: 128721

Prepared by: Michael Barrett

, Senior Chemist , ERB5 Amanda Solliday, Biologist

, ERB5 U. S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch IV 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460 Reviewed by: Keith Sappington, Senior Advisor, ERB5 Mohammed Ruhman, Senior Fate Scientist

, ERB5 Bill Shaughnessy Environmental Scientist, ERB 2 Brian Kiernan , Biologist , ERB 6 Mah Shamim , Branch Chief , ERB 5- 4 of 75 

### Table of Contents 1. Purpose

................................ ................................ ................................ ................................ ........ 5 2. Problem Formulation

................................ ................................ ................................ .................. 6 2.1. Nature of Regulatory Action

................................ ................................ ................................ 6 2.2. Previous Risk Assessments

................................ ................................ ................................ .. 7 3. Stressor Source and Distribution

................................ ................................ ................................ 8 3.1. Mechanism of Action

................................ ................................ ................................ ....... 8 3.2. Ove rview of Pesticide Use and Usage

................................ ................................ ............. 8 3.3. Environmental Fate and Transport

................................ ................................ ..................... 12 3.4. Bioaccumulation

................................ ................................ ................................ ............ 17 4. Receptors

................................ ................................ ................................ ................................ ... 17 4.1. Effects to Aqua tic Organisms

................................ ................................ ............................ 18 4.2. Effects to Terrestrial Organisms

................................ ................................ ........................ 22 4.3. Incident Database Review

................................ ................................ ................................ .. 26 4.4. Ecosystems Potentially at Risk

................................ ................................ .......................... 27 5. Assessment Endpoints

................................ ................................ ................................ .............. 28 6. Conceptual Model

................................ ................................ ................................ ..................... 28 6.1. Risk Hypothesis

................................ ................................ ................................ ................. 29 6.2. Conceptual Diagram

................................ ................................ ................................ .......... 29 7. Analysis Plan

................................ ................................ ................................ ............................ 31 7.1. Stressors o f Concern

................................ ................................ ................................ .......... 32 7.2. Measures of Exposure

................................ ................................ ................................ ........ 33 7.3. Measures of Effect

................................ ................................ ................................ ............. 36 7.4. Integration of Exposure and Effects

................................ ................................ .................. 36 7.5. Deterministic and Probabilistic Assessment Methods

................................ ....................... 37 7.7. Endangered Species Assessment

................................ ................................ ....................... 38 7.8. Drinking Water Assessment

................................ ................................ .............................. 39 7.9. Environmental Monitoring Data

................................ ................................ ........................ 39 8.0. Preliminary Identification of Data Gaps

................................ ................................ ............ 40 8.1. Environmental Fate

................................ ................................ ................................ ........ 40 8.2. Ecological Effects

................................ ................................ ................................ .......... 42 9. References

................................ ................................ ................................ ................................ . 46 Appendix A. Justi fication for Special Studies

................................ ................................ ............. 55 Appendix B. Chemical structures of halosulfuron

- methyl and selected environmental degradates

................................ ................................ ................................ ................................ ....................... 58 Appendix C. Aquatic Toxicity Predictions of Halosulfuron

- Methyl and Major Degradates from Structure

- Activity Relationships (SARs) using the ECOSAR Class Program and Review of Available Data

................................ ................................ ................................ .............................. 62- 5 of 75 1

. Purpose

The purpose of this problem formulation is to provide an understanding of the environmental fate and ecological effects of the registered uses of halosulfuron

- methyl (PC Code 128721). Halosulfuron

- methyl belongs to the sulfonylurea (SU) class of herbicides and is applied for selective control of annual and perennial broadleaf weeds and sedges at a variety of crop and

non

- crop sites. Crop registration sites include corn, cotton, nuts, rice, sorghum, soybeans, squash, sugarcane, and fruiting vegetables. In addition to the agricultural food uses, halosulfuron

- methyl is also registere d for use on turfgrass, ornamentals, and a variety of non

crop areas including, but not limited to, airports, cemeteries, fallow non

- crop areas, golf courses, landscaped areas, public recreation areas, residential and commercial lawns, sod or turf farms,

s ports fields, tennis courts, race tracks, fairgrounds, and rights

- of

- way. This herbicide can be applied as a pre

- and post

- emergence treatment, and tank

- mixed with other compatible herbicides to increase the weed control spectrum.

Halosulfuron

- methyl is an acetolactate synthase (ALS) inhibitor. ALS is an important enzyme for the synthesis of branched chain amino acids, and this metabolic pathway is present only in plants. Halosulfuron

- methyl is absorbed by the foliage and roots in plants.

Halosulfuron methyl is a sulfonylurea herbicide in which the sufonylurea moiety serves as a “bridge” between aminopyrimidine (the “R2” moiety on the

- NH

- side of bridge) and pyrazole (“R1” on the

- SO2

- side of bridge) ring structures in the molecule as shown below.

R1

- SO 2 - NH

- CO

- NH

- R2

Generic Molecular Structure for Sulfonylurea Herbicides

Halosulfuron Structure

This document will provide a plan for analyzing data relevant to halosulfuron

- methyl and for conducting environmental fate and ecological risk, endangered species, and drinking water assessments for its registered uses

. Additionally, this problem formulation is intended to identify- 6 of 75 data gaps, uncertainties, and potential assumptions used to address those uncertainties relative to characterizing the ecological risk associated with the registered uses of halosulfuron

- methyl

.

2

. Problem Formulation

2.1

. Nature of Regulatory Action

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), all pesticides distributed or sold in the United States generally must be registered by the Environmental Protection Agency (EPA)

. As part of determining whether a pesticide can be registered in the U.S., the Agency evaluates its safety to non

- target species based on a wide range of environmental and health effects studies. In 1996, FIFRA was amended by the Food Quality Protection Ac t, and the Agency was mandated to implement a new program for the periodic review of pesticides, i.e
., Registration Review ( http://www.epa.gov/oppsrrd1/registration_review/ )

. The Registration Review program is intended to ensure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health and the environment

. Changes in science, public policy, and pesticide use practices occur over time

. Through the Registration Review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely.

As part of the implementation of the Registration Review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the Agency is beginning its evaluation of halo sulfuron

- methyl to determine whether it continues to meet the FIFRA standard for registration

. This problem formulation for the environmental fate, ecological risk, endangered species, and drinking water assessment chapter in support of the Registration Review will be posted in the initial docket, which wil l open the public phase of the review process.- 7 of 75 2.2. Previous Risk Assessments

Halosulfuron

- methyl was first registered in 1994 for use on various crops including: corn, cotton, nuts, rice, sorghum, soybean, squash, sugarcane, and fruiting vegetables. Non

- crop uses are registered on turf, grasses grown for seed ornamentals, residential and commercial lawns, rights

of

- way and commercial premises and equipment. Like most sulfonylurea herbicides, halosulfuron

- methyl has a high potential to move off

- site by s pray drift, runoff and via wind

blown soil particles.

Because halosulfuron

- methyl was not registered until 1994, t he Agency did not prepare a Reregistration Eligibility Decision for this chemical

. The latest full ecological risk assessment for halosulfuron

- methyl was conducted in 2002 for a Section 3 new use on alfalfa within the
states of California, Arizona, Oklahoma, Texas, New Mexico, Kansas, Arkansas and Colorado with a maximum single appli cation rate of 0.047 lbs a.i./A (D313402). In that assessment, use of halosulfuron

- methyl did not result in acute or chronic risk f o r mammals, freshwater fish, aquatic invertebrates, or estuarine/marine invertebrates that exceeded Agency levels

- of

- concern

. Although chronic risk to birds could not be assessed at the time because avian reproduction studies had not been submitted, direct acute risk to avian species was not expected to be a

concern

. H alosulfuron

- methyl is classified as non

- toxic to terrestrial invertebrates on an acute contact basis. In the 2002 assessment, the primary ecological concern for halosulfuron is the direct acute risk to terrestrial and aquatic plants and the potential for indirect effects to aquatic and terrestrial animals through possible habitat alteration.

In December 2009, EFED conducted an ecological risk assessment for new use on soybeans (DP358030 and DP358032). Because of demonstrated concerns for effects on plants well outside treatment areas from spray drift for similar sulfonylurea herbicides, this assessment
p rovided new risk estimations for terrestrial and aquatic plants. Based on the single maximum application rate for soybeans (0.0625 lbs ai/A) for aerial and ground applications, the risk quotients (RQs) ranged from 13

- 520 for terrestrial plants, 110

- 2900 f or semi

- aquatic plants, 85

- 160 for aquatic vascular plants and 0.87

- 6.0 for algal species. Aerial application resulted in the higher RQs. Levels

- of

- concern were exceeded for listed and non

- listed terrestrial and aquatic plants. All risk conclusions for o ther taxa relied upon the 2002 assessment.

In May 2010, EFED completed the most recent Section 3 new use assessment of halosulfuron

methyl on dried shelled peas & beans (except soybean), succulent shelled peas & beans, apples, rhubarb, bushberry, fruiting vegetables and tuberous & corm vegetables ( D366537 )

. No changes were made to conclusions from the 2009 assessment because the application rate, number of applications and interval between applications were each similar to or less than currently registere d uses.- 8 of 75 For drinking water, the latest exposure assessment was conducted in August 2010 ( DP Barcode: D366411 ); estimated concentrations for this assessment remained the same as in the previous assessment in June 2009 ( DP Barcode: D358032 ). The acute exposure concentrations estimated with the FIRST model ranged up to 8.3 ppb or ug/L for halosulfuron

- methyl on corn and sugarcane. Chronic exposure (annual average EDWC) estimates were also calculated for the corn and sugarcane use pattern and r anged up to 1.7 ppb

. Tier 1 EDWC s for ground

- water (using the SCI

- GROW model) were significantly lower (0.065 ppb or less ).

3

. Stressor Source and Distribution

3.1. Mechanism of Action

Halosulfuron

- methyl belongs to the sulfonylurea herbicide family. The common mode of action for these herbicides is acetolactate synthase (ALS) enzyme inhibition in affected plant species. The ALS enzyme is important for the synthesis of branched chain amino acids (leucine, isoleucine, and valine). ALS inhibition in pla nts adversely affects plant growth and reproduction, most intensely in meristematically

- active tissues. Although acetolactate is present in mammals, the biosynthesis of branch chain amin o acids occurs only in plants and, i n general, SU herbicides are far less toxic to animals than plants.

3.2. Overview of Pesticide Use and Usage

Labeled Use

Halosulfuron

- methyl is a pre

- or post

- emergence herbicide and it is applied after emergence of target weeds. This herbicide selectively controls many weed species at ver y low rates including a variety of large

- and small

- seeded broadleaf weeds and annual and perennial sedges. Halosulfuron

- methyl is formulated as water dispersible granules and emulsifiable, flowable and soluble concentrates.

The maximum annual applicati on rate for any of the current uses is 0.125 lb ai/A, and single applications may be made at a rate as high as 0.094 lb ai/A (i.e., use on apple west of the Rockies)

. Table 1 provides a synopsis of the current use patterns

, noting that the registrant is asked to review the t able and correct the assumed numbers and clarify labels where factors such as minimum application intervals are not explicitly stated on the label.- 9 of 75

- Table 1

. Registered uses of halosulfuron

- methyl

Crop Use Pattern Single Application Rate (lbs a.i/A) Number Of Applic./

season Total Application Rate (lbs a.i/A)

d Minimum Application Intervals (days) PHI

c, d Minimum Maximum Season Year Days

Alfalfa (CA & AZ only) 0.031 0.047 2 0.094 0.094 NS NS Apples (east of the Rockies)3 0.023 0.047 2 0.094 0.094 NS 14 Apples (west of the Rockies) 0.023 0.047 2 0.094 0.094 NS 14 Apples (west of the Rockies) 0.023 0.094 1 0.094 0.094 NS 14 Asparagus 0.023 0.07 2 0.094 0.094 NS 1 Beans (dry) 0.023 0.047 2 0.047 0.094 NS NS Beans (Succulent snap beans incl. lima beans) 0.031 0.063 2 0.063 0.125 NA NS Beans and pea Dry shelled (east of the Rockies) 0.023 0.031 3 0.047 e 0.094 NS e 30 Beans and pea Dry shelled (West of the Rockies) 0.023 0.047 2 0.047 0.094 NS 30 Bushberry 0.023 0.047 2 0.094 0.094 45 60 Corn (Field for seed; non

- IR) 0.031 0.063 2 0.125 0.125 NS 30 Corn (Pioneer Hybrid IR for seed) 0.063 0.094 2 0.125 0.125 NS 30 Corn (Sweet and Pop) 0.031 0.047 2 0.078 0.078 NS 30

Cotton 0.031 0.063 1 0.063 0.063 NS 28

Cucurbits (Cucumbers) 0.023 0.047 2 0.047 0.094 NS 30 Cucurbits (Cantaloupes, Honeydews, Crenshaw & Melons) 0.023 0.047 2 0.047 0.094 NS 57 Cucurbits (Pumpkins, Winter Squash) 1) 0.023 0.047 2 0.047 0.094 NS 30 Cucurbits (Watermelons) h 0.023 0.047 2 0.047 0.094 NS 57 Fallow ground 0.031 0.063 2 0.125 0.125 NS NA Pea and bean, succulent shelled, subgroup 6B 0.023 0.023 1 0.023 0.023 NA NS

Rhubarb 0.023 0.047 2 0.047 0.047 NA 60- 10 of 75 Crop Use Pattern Single Application Rate (lbs a.i/A) Number Of Applic./

season Total Application Rate (lbs a.i/A)

d Minimum Application Intervals (days) PHI

c, d Minimum Maximum Season Year Days

Rice NS 0.063 2 0.063 a 0.063 NS 48 (69 in CA) Sorghum (Grain) NS 0.047 1 0.047 0.047 NA 30 Soybeans 0.031 0.063 2 0.125 b 0.125 NS NS Soybeans NS 0.063 2 0.125 0.125 150 NS Sugarcane 0.031 0.063 3 0.125 0.125 NS 30

Tree nuts 0.031 0.063 2 0.125 0.125 NS 1 Turf grass sod and seed farms 0.031 0.063 2 0.125 0.125 42 NA g Vegetable (tuberous and corm, subgroup l C) 0.023 0.047 2 0.047 0.047 NA 45 f Vegetables, Fruiting (Chile And Bell Peppers) 0.023 0.047 2 0.094 0.094 NS 30 Vegetables, Fruiting (including eggplant, tomatoes, peppers, & Okra) 0.023 0.047 2 0.094 0.094 NS 30

a This is the apparent intent of the label but it is not explicitly mandated on the label.
b This is the apparent intent of the label but it is not explicitly mandated on the label.

c NA = not applicable.
d NS = not specified.

e Although these are the limits stated on the label, the label also states “Make only one Sandea application per crop cycle”. It does not appear to be possible to have more than 2 crops per year.
f The label states “If needed, make a second post

- emergence foliar application 45 days before harvest” without any further elaboration.

g The label states “A second treatment may be required 6 to 10 weeks after the Initial treatment.”
h Only: AL, AR, AZ, CT, DE, FL, GA, IL, IN, KS, KY, LA,MA, MD, ME, MI, MO, MS, NC, NH, NJ, NY, OH, OK, PA, RI, SC, TN,TX, VA, V T, WV, WI- 11 of 75

- Label information requests

Label information that would help inform the risk assessment include: spe cific maximum application rate (per application and per year); maximum number of applications allowed; defined application intervals; ASABE S

- 572 droplet size spectra; and other drift management language.

Usage From 1998

- 2010, the crops with the most usag e in terms of total pounds of active ingredient applied were corn and rice accounting for about 83% of usage during this period 1

Figure 1 With the addition of several new uses in recent years, it is possible that other crop uses sites will increase in importance i n the future. Other registered uses include a large number of grain, fruit, and vegetable row crops, apples, and turf, fallow, and landscape uses. Possible geographic distribution and intensity of usage may be indicated from the acreage distribution of t he two crops with the highest usage: corn and rice. and Figure 2 2 show the distribution of planted acres for corn and rice crops, respectively, in the United States (2010 data in acres/county).

Figure 1

. Corn for all purposes a cres p lanted in the US in 20 10 (USDA

- NASS)

.

1 BEAD Chemical Profile for Registration Review: Halosulfuron

- methyl (128721) ; memorandum dated 9/2/2011.
2 Source: http://www.nass.usda.gov/Charts_and_Maps/Crops_County/index.asp#cs

.- 12 of 75

- Figure 2

. Rice acres planted in the US in 2010 (USDA

- NASS).

3.3

. Environmental Fate and Transport

The Agency has completed a review of all available data submitted by the registrant as part of registration review; the guidelines noted below are considered data gaps. At this time, the following environmental fate guidelines are not fulfilled for halosul furon

- methyl and are considered data gaps. The fate data gaps are:

**•** Aerobic soil metabolism (OPPTS guideline # 835.4100)

– additional data with supplemental study are needed to further investigate the change in soil metabolism rate with study conditions

.

**•** Hydrolysis (OPPTS guideline #835.2120)

– current study acceptable, but additional data are needed with a supplemental study to further investigate the change in rate with study conditions

.

A rational e for and details of these requirements are provided in Section 8.1. In general, as discussed below, the behavior of parent halosulfuron methyl is highly variable from site to site, as evidenced by the variance in results regarding its persistence and mobi lity between laboratory and field data and consequently data in addition to the minimum guidelines are requested under Guidelines 835.4100 and 835.2120.

Halosulfuron

- methyl has properties with regards to persistence and sorptivity that allow for a potenti al for residues to occur in ground and surface waters at some sites where conditions favor- 13 of 75

- greater persistence and mobility of the parent molecule

. S ome degradates of halosu lfuron

methyl may be present in the environment for months or longer (see Appendix A for chemical
structures and see Table 3 for a summary of conditions under which the degradates have been observed in significant amounts )

. The ide ntified degradates are also not included in the residues of concern for drinking or ecological exposure. A more complete environmental fate picture is provided below.

The environmental fate profile for halosulfuron

- methyl is complex

, indicating highly variable persistence, significant mobility in many soils, and/or the presence of a number of degradation products in the environment. A summary of halosulfuron

- methyl chemical and environmental fate properties is provided in Table 2 . A dditionally, a summary of the formation and decline of halosulfuron

- methyl degradation products is provided in Table 3

. Furthermore, direct studies with the degradates (available only for adsorption/desorption characteristics) are summarized in Table 4

.

Table 2

. Chemical and Physical Properties and Environmental Fate Properties of Halosulfuron

- methyl.
Parameter Value Reference (MRID #) /Comment Physical/Chemical Parameters CAS Registry Number 100184

- 20

- 1 47442201
Molecular mass 434.81 42139402 42139403 42139404 42661401 42661402 43237101 47442201 47442203 Vapor pressure (25°C) 0.0000001 (1 x 10E

- 7) Henry’s Law Constant (dimensionless, calculated) 1.08 X 10 - 09

Water solubility (25°C) (mg/L) 15 pH 5
1650 pH 7
Octanol

- water partition coefficient (Log K OW - 0.0186 (Kow= 1) ) Dissociation Constant (pKa) 3.44 Mobility Soil Partitioning Coefficient (K oc ) mL/g 31 to 199 in 4 soils: Drummer silt loam(Mollisol) = 94 Sarpy sandy loam (Entisol) = 114 Spinks loamy sand (Alfisol) = 199 Sable silty clay loam (unknown)= 31 42139411 41356336

Soil Partitioning Coefficient (K d 0.32 to 3.6 ) 42139411 41356336
Persistence in Water Hydrolysis half

- life (25°C, pH 5, 7, & 9); days pH 5 = 27 pH 7 = 14 pH 9 = 0.75 42139409 42846801 (Follow

- up)- 14 of 75

- Parameter Value Reference (MRID #) /Comment Aqueous photolysis half

- life (25°C); days Stable 42661409

Aerobic aquatic metabolism half

- life; days ND (study is currently in review) 45671701 Anaerobic aquatic metabolism half

- life; days 29 42661411
Persistence in Soil
Aerobic soil metabolism half

- life (25°C); days 11 to 16 (2 soils); DT90 values were 63 and 110 days. 42139410 42846802 (Follow

- up)

Soil photolysis 16.2 ( may be due to non

- photolytic degradation) 42661410

Field Dissipation Field dissipation half

- life; days 4 to 64 (7 sites) 42661412 42661413 42661414 42661415 (Stor. Stabil.) 42976302 42976303 42976304 43699801 Field dissipation half

- life; days (pipe lysimeter studies) 15

- 81 (2 sites with 4 treatment types per site) 42976303 and 42661414 Aquatic field dissipation total water and soil half

life in days (dry

- and wet

- field applied, respectively, for the LA and CA test sites.) Registrant used a non

- linear model to calculate as foll ows: LA: DT50 = 1.30, DT90 = 6.48 CA: DT50 = 1.87, DT90 = 12 Half

- life 7.2 to 14.5 days using pseudo 1 st 44437304

order model. Aquatic Bioconcentration Bioconcentration Factor (BCF) in fish No Data None

Bioconcentration Factor (BCF) in crayfish No Data None

Table 3

. Summary of formation and decline information on halosulfuron methyl degradates from environmental fate studies.
Degradate: > 10% for 3 months or more? (Maximum % of applied in parenthesis; time periods are in days or months after the application of halosulfuron

- methyl to the soil or water)
Study 3

- chlorosulfonamide
ester 3

- chlorosulfonamide acid Aminopyrimidine halosulfuron

methyl guanidine halosulfuron

methyl rearrangement ester

Hydrolysis (1

- month study) Persistent, low pH

-- Persistent low pH

-- Persistent, high pH- 15 of 75

- Degradate: > 10% for 3 months or more? (Maximum % of applied in parenthesis; time periods are in days or months after the application of halosulfuron

- methyl to the soil or water)
Study 3

- chlorosulfonamide
ester 3

- chlorosulfonamide acid Aminopyrimidine halosulfuron

methyl guanidine halosulfuron

methyl rearrangement ester

Aerobic soil Yes, 1 of 2 soils (up to 29%) Yes, 1 of 2 soils (up to 32%) Yes, 1 of 2 soils (up to 27%) Yes, 1 of 2 soils (up to 15%) No (up to 11%)

Anaerobic aquatic soil Yes (up to 92%) No Yes (up to 78%) No No

Field "pipe" lysimeter, IA Yes (up to 19%, & up to 11% at 4 months) No. (always <8%) No (usually <5% max.) No No (but up to 28% as late as 4 months) 1

Field "pipe" lysimeter, NC No (but up to 24% in 1 st No (but up to 18% in 1 30 days). st No (but up to 18% in 1 30 days) st No 30 days) No

Traditiona l field dissipation (164

- 1) Residues of each of the degradates were below the quantification limit of 5 ppb; field persistence cannot be evaluated from these studies.

Soil photolysis
2 (1

- month study) Persistent, up to 37% No Persistent, up to 36% No No

Aqueous photolysis

(1

- month study) 5 Persistent, up to 31% No Persistent, up to 28% No No

1 Substantial amounts of rearrangement acid were found (Up to 21% in one treatment), total amounts of rearrangement acid plus rearrangement ester were often 20 to 30% of the applied halo sulfuron

- methyl from columns analyzed over the first 4 months.

2 Most of the degradation did not appear to be due to photolysis.- 16 of 75

- Table 4

. Summary of direct environmental fate studies with halosulfuron

- methyl degradates.
Parameter Value Reference (MRID #) /Comment Soil Partitioning Coefficient (K d (degradation products) ) chlorosulfonamide acid,

- 0.03 to 0.16 chlorosulfonamide ester : 0.75 to 6.85

a minopyrimidine : 2.32 to 165.6 42139411

In the two available aerobic soil metabolism studies

, there was relatively rapid degradation of halosulfuron

- methyl. Both aerobic soil metabolism half

- lives and hydrolysis rates were only a few weeks under the conditions tested ( Table 2 ). Hydrolysis rates may be significantly slower at lower pH and lower temperatures than tested and may also be affected by the complex soil matrix under field conditions

. At least one published study suggests that the hydrolysis rate for this molecule may be slower than under either mildly acidic or mildy alkaline conditions. 3 In the field dissipation studies there are clear indications of very long (i.e., up to two or t hree years) persistence of halosulfuron residues at some sites. First, in some of the field studies a significant portion of the applied halosulfuron

- methyl persisted for several months or longer. Here a pseudo first

- order kinetic model poorly described the data and severely under predicted the residue levels remaining several months to a year or more after application. Additionally, possible recognition of the danger of residues persisting at phytotoxic levels for an extended period is captured in label restrictions that prohibit rotation into many crops for up to 3 years after the last application of halosulfuron

- methyl.

Halosulfuron

- methyl is quite mobile in most soils. Soil organic carbon partition coefficients (K oc s ) for halosulfuron

- methyl parent were 31 to 199 in four soils; the median value was 104. If the median mobility and persistence values in these studies are representative of the behavior of halosulfuron

- methyl in the majority of the prospective use area, then halosulfuron

- methyl would only have a modest leaching potential in the majority of the use area. It is important to note that the degree of adsorption in soils may have a correlation with soil pH (i.e., tendency for lower K d or other sorption coeffic ients with increasing pH) similar to the behavior of other sulfonylureas that are weak acids. However, soil organic carbon content also appears to be an important factor in determining the degree of adsorption/desorption 4

.

Halosulfuron

- methyl can apparen tly be both mobile and highly persistent in at least some soils and is probably more likely to be both in more alkaline soils. Field dissipation rates at some study sites were slower than the metabolism rates measured in laboratory studies ( Table 2 ). Dissipation rates may be faster than degradation rates because some loss of pesticide from the

3 Zheng, W., S

. R. Y ates, and S

. K. P apiernik. Transformation Kinetics and Mechanism of the Sulfonylurea Herbicides Pyrazosulfuro n Ethyl and Halosulfuron Methyl in Aqueous Solutions J. Agric. Food Chem. 2008, 56, 7367

– 7372

. 4 Among the published references on this subject is a study specifically directed at this variability for halosulfuron

methyl: Kuwatsuka, D .S. and I. Yamamoto. 1997. Journal of Pesticide Science Vol.22(4):288

- 292.

- Relationships between Soil Properties and Sorption Behavior of the Herbicide Halosulfuron

- methyl in Selected Japanese Soils.- 17 of 75

- treated zone of soil may be by mechanisms other than degrad ation (leaching, volatilization, irreversible adsorption, runoff, and lateral movement)

. H owever, the dissipation rate cannot be more rapid than the degradation rate in the field

, because degradation is one of the dissipation
processes.

Of several environ mental degradates all are fragments of the parent molecule (i.e., containing either the pyrimidine or pyrazole moieties, but not both due to cleavage of the sulfonylurea bridge) with the exception of the "halosulfuron

- methyl rearrangement ester", sometimes referred to as "RRE" or "MON 5781." This product results from the abstraction of the S0 2 NHCO moiety between the rings, such that the pyrimidine and pyrazole rings are then joined together only by an NH group. These degradates are not included in the eco logical or drinking water residues of

concern.
For additional details on the environmental fate, the reader is referred to the most comprehensive previous review of halosulfuron as provided in an August 13, 2002 Risk Assessment (including drinking water) by EFED (DP Barcode D278449 5 ); subsequent assessments rely upon this environmental fate review.

3. 4

. Bioaccumulation

There are no bioconcentration or bioaccumulation studies for halosulfuron

- methyl in fish or other aquatic animals. However, the chemical properties of halosulfuron

- methyl (e.g., soil Koc less than 200, Kow= 1 ) imply a low bioconcentration potential

. T herefore, these studies are not required.

4

. Receptors

Consistent with the process described in the Overview Document (USEPA 2004), the risk assessment for halo sulfuron

- methyl r elies on a surrogate species approach

. Toxicological data generated from surrogate test species are used to extrapolate the potential effects on a variety of species (receptors) included under these taxonomic groupings

. Available studies are classified as acceptable, supplemental or invalid, depending upon the suitability of the data for risk assessment purposes

. Acute and chronic toxicity data from studies submitted by the pesticide registrant, along with the available open literature, will be used to evaluate the potential direct and indirect effects of halosulfuron

- methyl to aquatic and terrestrial receptors. Open literature studies are primarily identified through EPA’s ECOTOX database, which employs a literature search engine for locating chemical toxicity data for aquatic and terrestrial plants and wildlife

. This includes toxicity on the technical grade active ingredient, degradates, and when available, formulated products

. The evaluation of both sour ces of data may also provide insight into the direct and indirect effects of halosulfuron

- methyl usage on biotic communities from loss of species that are

5 DP Barcodes: D278449; D273885; D261707; D271575. Expanded Section 3 and I R

- 4 Uses To Add Asparagus, Flowering Vegetables and Beans to Halosulfuron

- methyl Label (August 14, 2002).- 18 of 75

- sensitive to the chemical and from changes in structure and functional characteristics of the affecte d communities

. A summary of the aquatic and terrestrial toxicity data available for the species most sensitive to halosulfuron

- methyl is provided in Sections 4.1 and 4.2, respectively. In addition, a summary of ecological incidents associated with halo sulfuron

- methyl and a description of ecosystems potentially at risk are provided in Sections 4.3 and 4.4, respectively.

Toxicity to fish

, aquatic

- phase amphibians and aquatic invertebrates is categorized using the system shown in Table 5 (US EPA, 2004)

. Toxicity to terrestrial fauna (birds , reptiles, terrestrial

- phase amphibians and mammals) is categorized using the system shown in Table 6

. Toxicity categories for plants have not been defined.

Table 5

. Categories of Acute Toxicity for Aquatic Animals
LC 50 (ppm) 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 Toxicity 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

If open literature toxicity studies for halosulfuron

- methyl are identified through ECOTOX, they will be reviewed for the risk assessment.

4.1

. Effects to Aquatic Organisms

The most sensitive of the available aquatic toxicity data from registrant

- submitted studies are provided in Table 7

.

Based on the available information, halosulfuron

- methyl technical is classified as no more than slightly toxic to fish and invertebrates on an acute exposure basis. No aquatic toxicity data is available for halosulfuron

- methyl typical end

- use products on fish or aquatic invert ebrates. Available data indicate both vascular and nonvascular aquatic plants are affected by halo sulfuron

- methyl at low levels of exposure.- 19 of 75

- Table 7

. Aquatic Toxicity Profile for Halo sulfuron

- methyl

Taxonomic Group S pecies Endpoint Acute Toxicity Classification MRID Reference and Study Classification

Freshwater fish Lepomis macrochirus (Bluegill sunfish) 96

- hour LC 50 > 118 mg a.i./L Practically nontoxic 42661422 Acceptable

Oncorhynchus mykiss (rainbow trout) NOAEC = 34 mg a.i./L LOAEC = 106 mg a.i./L --- 43493001 a Acceptable

Freshwater invertebrates Daphnia magna ( Water flea ) EC 50 > 107 mg a.i./L Practically nontoxic 42661423 Acceptable

NOAEC = 0.98 mg a.i./L LOAEC = 1.8 mg a.i./L --- 43493003 a Acceptable

Estuarine/marine fish Cyprinodon variegatus (Sheepshead

minnow) LC 50 Practically nontoxic >125 mg a.i./L 42773001 Supplemental

Estuarine/marine invertebrates Crassostrea virginica ( Eastern oyster ) and Americamysis bahia ( Mysid shrimp ) EC 50 = 94 mg a.i./L (oyster)

EC 50 = 109 mg a.i./L (shrimp) Slightly toxic to practically nontoxic 42773003, Acceptable and 42773002, Acceptable

Vascular aquatic plants Lemna gibba (duckweed) EC 50

NOAEC = 0.023 μg a.i./L = 0.042 μg a.i./L

--- 43330701 b Acceptable

Nonvascular aquatic plants Pseudokirchneriella subcapitata ( Green algae ) EC 50

NOAEC = 0.63 μg a.i./L = 4.1 μg a.i./L

--- 43330702 b Acceptable

a Chronic toxicity categories have not been defined.
b Toxicity categories for plants have not been defined.

On an acute basis, halosulfuron

- methyl is practically non

- toxic to freshwater and estuarine/marine fish. T he 96

- hour LC Fish

50 > 118 mg a.i./L for bluegill sunfish and 96

- hour LC 50 > 131 mg a.i./L for rainbow trout (MRIDs 42661422 and 42661423). For both acute studies with freshwater fish, no effects were observed at any treatment level. For the estuarine/marine test species, sheepshead minnow, the 96

- hour LC 50 > 125 mg a.i./L (MRID 42773001). However, this study was classified as supplemental in formation because a precipitate formed at in the test solution and it is unclear from the study report if the solids were included in the analytical samples. No treatment

- related effects were observed at any test concentration. An additional study is not requested at this time, because the bioavailable fraction of halosulfuron

- methyl in- 20 of 75

- this study would have to be approximately 5 orders of magnitude lower than the measured concentrations to approach the maximum peak expected exposure concentration of 5.68 μg a.i./L estimated in the previous risk assessments ( DP358030 and DP358032 ).

In addition, the registrant submitted two additional acute fish studies, one with rainbow trout and one with bluegill sunfish. These studies were determined to be supplemental information only, due to lack of confidence in the measured chemical concentrations as a result of the poor solubility of the test material

.

Based on a submitted early

- life stage study with rainbow trout, chronic effects to freshwater fish, such as reductions in post

- hatch length and weight, were observed at higher levels of exposure to halosulfuron

- methyl

. In this study, the NOAEC is 34 mg a.i./L and a LOAEC is 106 mg a.i./L ( 43493001).

No data have been submitted that examine the chronic e ffects of halosulfuron

- methyl to estuarine/marine fish. However, there is no indication of increased a sensitivity of estuarine/marine fish compared to freshwater fish , as halosulfuron

- methyl was practically nontoxic to both taxa on an acute basis

. There fore

, the available data does not suggest that a greater sensitivity to halosulfuron

- methyl for estuarine/marine fish species on a chronic basis would exist

.

On an acute basis, halosulfuron

- methyl is practically non

- toxic to freshwater and estuarine/marine invertebrates. In a study with freshwater daphnids, the 48

- hour EC Aquatic Invertebrates

50 was greater than 107 mg a.i./L (MRID 42661423). In studies with estuarine/marine inver tebrates , the 48

- hour EC 50 was 109 mg a.i./L for mysid and the 48

- hour EC 50 was 94 mg a.i./L for the eastern oyster (MRIDs 42773002 and 42773003).

In a chronic study with freshwater daphnids, the NOAEC was 0.98 mg a.i./L and LOAEC was 1.8 mg a.i./L , based on reduced length of the test organisms ( 43493003 ). In another chronic study with daphnids

, t he NOAEC could not be determined due to the adverse effects observed at all treatment levels. The LO A EC was 6. 9 mg a.i./L, the lowest concentration tested

, based on effects to growth and offspring production (MRID 43493002).

No data have been submitted that examine the chronic effects of halosulfuron

- methyl on estuarine/marine invertebrates. However, there is no indication of increased sensitivity of
estuar ine/marine invertebrates compared to freshwater invertebrates, as halosulfuron

- methyl was practically nontoxic to both taxa on an acute basis. The level at which no adverse effects were observed in the chronic freshwater study with aquatic invertebrates, 0.98 mg a.i./L, is over 2 orders of magnitude higher than the maximum 21

- day expected exposure concentration of 5.43 μg a.i./L estimated in the previous risk assessments ( DP358030 and DP358032 ). Therefore, additional chronic data for estuarine/marine inve rtebrates is not requested at this time.

Vascular and Nonvascular Aquatic Plants- 21 of 75

- Halosulfuron

- methyl exhibits phytotoxic activity towards aquatic vascular and nonvascular plants. In a study with halosulfuron

- methyl technical, the EC 50 was 0.042 μg a.i./L for duckweed ( Lemna gibba ) , based on frond counts and nominal concentrations at a pH of 6.4 (MRID 43330701). The registrant submitted a nother study examining the effects of halosulfuron

- methyl technical on Lemna gibba and this study is in review (MRID 46004101 ). Four algal toxicity studies are available for the chemical, with a n EC 50 range from 4.1 μg a.i./L for freshwater algae ( Selenastrum capricornutum ) , 110 μg a.i./L for the freshwater algae ( Anabaena flos

- aquae ), >350 μg a.i./L for the freshwat er diatom ( Navicula pelliculosa ) to >400 μg a.i./L for the marine diatom ( Skeletonema costatum ) (MRIDs 43330702, 43330703, 43330704 and 43330705).

V arious degradates of parent halo sulfuron have been identified from the various fate studies, as previously highlighted in Table 3 . From the list of degradates that have been identified, only five of them are considered major degradates with formation rates at or above 10% of the applied parent compound. The structures o f these four halosulfuron methyl metabolites with demonst rated environmental persistence were entered into the ECOSAR v.1.0 model

. These metabolites are halosulfuron aminopyrimidine (CP 17477), 3

- chlorosulfonamide ester (CP 147925), 3

- chlorosulfonamide aci d (CP 147924) and the halosulfuron rearrangement ester (CP 151790). For context, the parent model is also included in the predicted toxicity analysis. The ECOSAR output and parameterization with available toxicity information are included in Appendix C

. Degradate Toxicity to Aquatic Organisms

C leavage of the sulfonylurea bridge (

- NH

- CO

- NH

- SO2

- ) between the two ring structures in the parent compound is predicted to result in degradates that are either not phytotoxic or require relatively higher residues to affect plant growth. This assumption is supported by the predicted toxicity results, which indicate lower degradate toxicity to algae, as compared to the parent compound. The halosulfuron rearrangement ester (CP 147925 or CP 151790) contains a contracted sulfonylurea bridge, but this compound is also predicted to be substantially less toxic than the parent compound to aquatic taxa.

Based on the results of this analysis, the degradates of halosulfuron

- methyl have lower predicted toxicity to other aquatic organisms than the parent compound. One ex ception is the predicted toxicity of the degradate halosulfuron aminopyrimidine to daphnids. The predicted toxicity for the aniline structure in this compound is 2.4 mg/L, compared to 20 mg/L predicted toxicity for the pyrazole structure of halosulfuron me thyl. These are the lowest (most sensitive) ECOSAR

predicted values for each compound. However, this toxicity estimate for halosulfuron aminopyrimidine is still substantially lower than the predicted exposure aquatic estimates for the parent compound in pr evious assess ments , and the formation of halosulfuron aminopyrimidine is expected to form at even lower concentrations than the parent compound

.

See Section 7.1 Stressors of Concern of this document for more information on how the degradate compounds will be analyzed in the upcoming risk assessment.- 22 of 75

- 4.2

. Effects to Terrestrial Organisms

Table 8 summarizes the most sensitive terrestrial toxicity endpoints for halo sulfuron

- methyl

, based on an evaluation of the submitted data

. Summary

Halosulfuron

- methyl is classified as practically nontoxic to terrestrial birds based on the available acute oral and subacute dietary exposure studies. A n acute oral study with a passerine species is not requested at this time for the upcoming ecological r isk assessment

. The submitted reproductive studies for this chemical also indicate low chronic toxicity to birds. Halosulfuron

methyl is classified as practically nontoxic to mammals on an acute oral exposure basis

. C hronic effects were observed in submitt ed developmental toxicity studies with rats and rabbits , but at levels that were higher than predicted exposure concentrations. Halosulfuron

- methyl is classified as practically nontoxic to honey bees ( Apis mellifera ) on an acute contact exposure basis. H a losulfuron

- methyl causes adverse effects on terrestrial plants at low levels of exposure.

Table 8

. Terrestrial Toxicity Profile for Halo sulfuron

- methyl

.

Taxonomic

Group Surrogate Species (Common Name) Endpoint Acute Toxicity Classification MRID Reference and Study Classification

Birds C olinus virginianus (Bobwhite quail) LD 50 Practically nontoxic > 2210 mg ai/kg bw 42139434 Acceptable

Colinus virginianus (Bobwhite quail) and Anas platyrhynchos (mallard duck) LC 50 Practically nontoxic >5620 mg ai/kg diet 42139435, Acceptable and 42139436, Acceptable

Colinus virginianus (Bobwhite quail) and Anas platyrhynchos (mallard duck) NOAEC = 1010 mg a.i./kg diet

LOAEC > 1010 mg a.i./kg diet --- a 47792801, Acceptable and 47792802, Acceptable

Mammals Rattus norvegicus (Laboratory rat ) LD 50
(males) = 3170 mg/kg Practically non toxic 42139414 Acceptable

(rabbit ) Oryctolagus

cuniculus NOAEL = 50 mg ai/kg/day --- 42139426 a Acceptable- 23 of 75

- Taxonomic

Group Surrogate Species (Common Name) Endpoint Acute Toxicity Classification MRID Reference and Study Classification

LOAEL = 150 mg ai/kg/day Terrestrial Invertebrates Apis mellifera (Honey bee) LD 50 Practically nontoxic (contact) > 98.2 μg a.i./bee 42139440 Acceptable

Terrestrial Plants Monocots

– ryegrass, corn, oat, onion (most sensitive in

seedling emergence and vegetative vigor)

Dicots

– soybean, tomato, cucumber,

cabbage, lettuce (most sensitive in seedling emergence) and radish (most sensitive in vegetative vigor) Seedling
emergence

Monocots EC 25

NOAEC = 0.000094 lbs a.i./A = 0.000 6 3 lbs a.i./A

Dicots EC 25

NOAEC = 0.000012 lbs a.i./A = 0.000020 lbs a.i./A --- 42661424 (addendum 43195501), Acceptable b

Monocots Vegetative vigor

EC 25

NOAEC = 0.000035 lbs a.i./A = 0.00075 lbs a.i./A

Dicots EC 25

NOAEC = 0.000018 lbs a.i./A = 0.000057 lbs a.i./A --- 42661425 (addendum 43195502), Acceptable b

a Chronic toxicity categories have not been defined.
b Toxicity categories for plants have not been defined.

The results of the single acute oral toxicity study available for halosulfuron

- methyl indicate that the chemical is practically non

- toxic to avian species on an acute oral basis. The acute oral LD Birds

50 value for bobwhite quail ( Colinus virginianus ) is >2 21 0 mg a.i./kg bw , based on nominal concentrations and corrected for percent active ingred ient of the test substance (MRID 42139434, acceptable ). No mortality was observed at any treatment level. At the lowest and the second highest dose (287 and 1326 mg ai/kg bw) of five treatment levels, observations of toxicity effects included lethargy, d epression, reduced reaction to external stimuli,- 24 of 75

- submissiveness, wing droop, loss of coordination, lower limb weakness, prostrate posture, shallow and rapid respiration and convulsions on Day 0 following dosing. No weig ht loss or feed consumption was obse rved in any treatment level, compared to the control birds.

No acute av ian oral study with halosulfuron

- methyl has been submitted for passerine species. However, additional acute oral data with a passerine species is not requested at this time. Due to the low application rates for halosulfuron

- methyl, the modeled peak dose

- based exposure concentrations for birds (36 mg a.i./kg bw based on 2 application at the maximum rate of 0.125 lbs a.i./A) is two orders of magnitude lower than the levels at which no mortality was observed in the submitted acute oral study with bobwhite quail ( 2 21 0 mg a.i./kg bw ). Therefore, information on the toxicity of halosulfuron

- methyl to additional avian species is unlikely to influence the upcoming ecological risk assessment c onclusions.

The results of the two sub

- acute dietary toxicity studies available for halosulfuron

- methyl indicate that it can be classified as practically non

- toxic to avian species on a short

- term dietary basis. The LC 50 is greater than 5620 mg a.i./kg bw for bobwhite quail ( Colinus virginianus ) (MRID 42139436). In a dietary study conducted with mallard ducks ( Anas platyrhynchos ), the LC 50 is also greater than 5620 mg a.i./kg bw (MRID 42139435). In both submitted avian dietary studies, the NOAEC was 5620 mg a.i./kg body weight

, based on no observations of mortality or other sublethal effects.

No treatment

- related effects were observed in the submitted reproduction studies with either bobwhite quail ( Colinus virginianus ) or mallard ducks ( Anas platyr hynchos ) at measured test concentrations up to 1010 mg a.i./kg diet (MRIDs 47792801 and 47792802).

A number of mammalian toxicity studies have been submitted for halosulfuron

- methyl. Two acute oral studies are available, conducted with the labora tory rat. In the submitted study with halosulfuron

- methyl technical, the LD Mammals

50 > 10,435 mg a.i./kg bw in males, LD 50 > 7758 mg a.i./kg bw in females and LD 50 > 8866 mg a.i./kg bw for both sexes combined (MRID 42139413). In another submitted acute oral stud y, rats were exposed to the halosulfuron

- methyl product MON 12051 (50% active ingredient), resulting in an LD 50 = 3170 mg a.i./kg bw in males, LD 50 > 6000 mg a.i./kg bw in females and LD 50 > 4704 mg a.i./kg bw for both sexes combined (MRID 42139414).

Inha lation and dermal toxicity studies were also submitted for laboratory rats. Two acute dermal studies were conducted on the laboratory rat. In the submitted study with halosulfuron

- methyl technical, the LD 50 >2000 mg ai/kg bw for each sex (MRID 42139415). In another submitted dermal study with the product MON 12051, the LD 50 >5000 mg a.i./kg bw for each sex (42139416). Two inhalation studies with halosulfuron

- methyl are also available. In the submitted inhalation study with halosulfuron

- methyl technical, the LD 50 was greater than 6.0 mg ai/L for each sex (MRID 42139417). In another submitted inhalation study with the product MON 12051, the LD 50 >4.8 mg a.i./kg bw for each sex (42139418).- 25 of 75

- Based on the available submitted studies examining the acute effe cts of halosulfuron

- methyl and the product MON 12051 to rats, the chemical shows low toxicity via oral, dermal and inhalation routes of exposure.

Several chronic mammalian studies have also been submitted for halosulfuron

- methyl. In two developmental tox icity studies, halosulfuron

- methyl technical was administered orally by gavage to two different species

– laboratory rats (dose administered on gestation days 6 though 15) and rabbits (dose administered on gestation days 6 through 19)

. In the rat study, the NOAEL = 250 mg a.i./kg/day and LOAEL = 750 mg a.i./kg/day based on decreases in maternal body weight gain, maternal food consumption, litter size and fetal body weight (MRID 42139425). Rabbits appear to be more sensitive than rats to chronic exposures of halosulfuron

- methyl, with a NOAEL = 50 mg a.i./kg/day and a LOAEL = 150 mg a.i./kg/day based on decreases in maternal body weight gain, maternal food consumption and litter size (MRID 42139426). When the results of these toxicity studies are adjusted for the weight of the typical ly

- modeled mammals (15 g, 35 g and 1000 g), the adjusted NOAELs are 110, 89 and 38 mg a.i./kg bw, respectively. These adjusted NOAELs are higher than the modeled peak dose

- based exposure concentrations for mammals, 54, 37 and 9 m g a.i./kg bw for the 15 g, 35 g and 1000 g mammals, respectively (based on 2 application at the maximum rate of 0.125 lbs a.i./A). Therefore, chronic dietary risk concerns for mammals are not expected based on this preliminary screen, using the maximum
ap plication rate of halosulfuron

- methyl and most sensitive chronic mammalian toxicity endpoint available.

In a multigenerational reproductive study with rats, dietary exposure of halosulfuron

- methyl technical resulted in a NOAEL = 800 mg a.i./kg diet and a LOAEL = 3600 mg a.i./kg diet, based on decreases in body weight and food consumption of both parental sexes (MRID 42139427). No reproductive effects (effects to offspring) were observed at the highest test concentration of 3600 mg a.i./kg diet.

A single study examining the effects of halosulfuron

- methyl on terrestrial invertebrates has been submitted. In an acute contact study with honey bees, the LD Terrestr ial Invertebrates

50 > 98.2 μg a.i. /bee , corrected for percent active ingredient of the test subst ance (MRID 42139440). M ortality of bees did not exceed 4% in either the negative or solvent control, or any treatment level.

Phytotoxic effects to terrestrial plants are observed at exposure levels of halosulfuron

- methyl several orders of magnitude lower than label rates. In a submitted seedling emergence study, the most sensitive EC Terrestrial Plants

25 = 0.00002 lbs ai/A, based on effects to lettuce dry weight (MRIDs 42661424 and 4 3195501). Both monocots and dicots were affected by low levels of exposure to halosulfuron

- methyl. For the most sensitive monocot species, onion, the EC 25 is 0.000 6 3 lbs a.i./A and the NOAEC is 0.000094 lbs a.i./A based on reductions in plant dry weight.

In vegetative vigor toxicity studies, radish was the most sensitive species, with an EC 25 = 0.000057 lbs ai/A and NOAEC of 0.000018 lbs a.i./A , based on adverse effects to plant dry- 26 of 75

- weight (MRIDs 42661425 and 43195502). For the most sensitive monocot species, onion, the EC 25 is 0.00075 lbs a.i./A and the NOAEC is 0.000035 lbs a.i./A based on reductions in plant dry weight. The overall toxicological sensitivity of the tested plant species indicates that many nontarget plant species may be susceptible if exposed to halosulfuron

- methyl

.

4.3

. Incident Database Revi ew

A review of the Ecological Incident Information System (EIIS, v. 2.1) and Aggregate Incident databases for ecological incidents involving halosulfuron

- methyl was completed on September 6, 2011. This database consists of exposure incident reports submitted to the EPA from 1994 to present. A search for halosulfuron

- methyl was also conducted in the American Bird Conservancy’s Avian Incident Monitoring System (AIMS), which contains publicly availabl e data on reported avian incidents involving pesticides :

( http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm ).

No incidents for halosulfuron

- methyl we re reported in either the EIIS or the AIMS database.

The number of reports listed in the EIIS database is believed to be only a small fraction of the total incidents involving organism mortality and damage caused by pesticides. Few resources are assigne d to incident reporting. Reporting by states is only voluntary, and individuals discovering incidents may not be informed on the procedure of reporting these occurrences. M uch of the database is generated from registrant

- submitted incident reports. In a ddition, incident reports for non

- target organisms typically provide information only on mortality events and plant damage incidents. Except for phytotoxic effects in terrestrial plants, sublethal effects for organisms such as reduced growth or impaired r eproduction are rarely reported. Because of these logistical difficulties, EIIS is most likely a minimal representation of all pesticide

- related ecological incidents.

Registrants are legally required to provide detailed reports of only “major” ecological incidents involving pesticides, while “minor” incidents are reported aggregately. Based on 40 CFR §159.184, an ecological incident is considered major and must be submitted to the Agency by the registrant if any of the following criteria are met:

Fish o r wildlife: (A) Involves any incident caused by a pesticide currently in Formal Review 6

(B) Fish: Affected 1,000 or more individuals of a schooling species or 50 or more individuals of a non

- schooling species. for ecological concerns.

6 Formal Review means Special Review, Rebuttable Presumption Against Registration (RPAR), FIFRA section 6(c) suspension proceeding, or FIFRA section 6 (b) cancellation proceeding, whether completed or
not.- 27 of 75

- (C) Birds: Affected 200 or more individuals of a flocking species, or 50 or more individuals of a songbird species, or 5 or more individuals of a predatory species. (D) Mammals, reptiles, amphibians: Affected 50 or more individuals of a relatively common or herding species or 5 or more individuals of a rare or solitary species. (E) Involves effects to, or illegal pesticide treatment (misuse) of a substantial tract of habitat (greater than or equal to 10 acres, terrestrial or aquatic). Plants : (A) The effect is alleged to have occurred on more than 45 percent of the acreage exposed to the pesticide.

All ecological incidents classified as ‘minor’ only need to be aggregately reported as quarterly counts of incidents by the registrant(s). Ecological incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (W

- B), ‘minor plant’ (P

- B), and ‘other

non

- target’ ( ONT) incidents. ‘Other non

- target’ incidents include reports of adverse effects to insects and other terrestrial inver tebrates.

For halosulfuron

- methyl , two minor plant incidents have been reported

. The first reported incident occurred in 1999 , and involved the product Permit. The second reported incident involved Manage Turf Herbicide, and occurred in 2000. Unless additional information on these aggregated incidents becomes available, they will be assumed to be representative of registered uses of halosulfuron

- methyl in the risk assessment.

4.4

. Ecosystems Potentially at Risk

The ecosystems at risk are ofte n extensive in scope; therefore, it may not be possible to identify specific ecosystems during the development of a nation

- wide ecological risk assessment

. However, in general terms, terrestrial ecosystems potentially at risk could include the treated fie ld and immediately adjacent areas that may receive drift or runoff

. Areas adjacent to the treated field could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats and other uncultivated are as

. Aquatic ecosystems potentially at risk in clude water bodies adjacent to or downstream from the treated field and could include impounded bodies such as ponds, lakes and reservoirs, or flowing waterways such as streams or rivers

. For uses in coastal areas, aquatic habitat also includes marine ecosystems, including estuaries

.- 28 of 75

- 5

. Assessment Endpoints

Assessment endpoints are defined as “explicit expressions of the actual environmental value that is to be protected.” 7 Selection of the assessment endpoints is based on valued entities (fish, birds

, etc. ), the ecosystems potentially at risk (such as water bodies, riparian vegetation, and upland habitats), the migration pathways of halosulfuron

- methyl ( runoff, drift, etc .), and the
rout es by which ecological receptors are exposed to halo sulfuron

- methyl (direct contact, dietary exposure, inhalation, etc. )

. Assessment endpoints for halo sulfuron

- methyl include direct toxic 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 surr ogate entity or attribute in response to exposure to a pesticide

. Specific 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 numb er 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 must 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 receptor. For an ecological pathway to be complete, it must have a source, a release mechanism, an environmental transport medium, a point of
exp osure for ecological receptors, and a feasible route of exposure.

The conceptual model for halo sulfuron

- methyl provides a written description (risk hypothesis) and visual representation (conceptual diagram) of the predicted relationships between halo sulfu ron

- methyl , potential 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 1998b).

Based on the available data (including those fro m valid but limited studies, and considering existing data gaps), the persistence of halosulfuron

- methyl in the environment is highly variable. Laboratory and field studies showed that persistence in some soil environments was significantly greater than w ould be predicted from the hydrolysis rates measured in laboratory studies. Although the measured hydrolysis rates were more rapid at higher pH levels (e.g., 0.5 day half

life at pH 9), there was no consistent correlation between the measured soil pH and the degradation rate in aerobic soil or the dissipation rate in field studies. Also as noted previously at least one published study suggests that the hydrolysis rate may not consistently increase with increasing pH. Although the submitted hydrolysis stu dy has been previously accepted, it is recommended that a more detailed follow

- up study be conducted to more fully assess the hydrolysis rate of halosulfuron

- methyl at different temperatures and pH levels and the formation

7 From U.S. EPA (1992). Framework for Ecological Risk Assessment. EPA/630/R

- 92/001.- 29 of 75

- of hydrolysis products. These dat a can be used to more accurately parameter many exposure prediction models. Halosulfuron

- methyl is highly mobile (Koc range 31 to 199) and has significant potential for runoff at sites where it is more persistent and may leach significantly at sites where hydrolysis is a relatively insignificant route of dissipation in topsoil and subsoil. Halosulfuron

- methyl is not expected to bioaccumulate in aquatic or terrestrial food chains.

6.1

. Risk Hypothesis

A risk hypothesis describes the predicted relationship among the stressor, exposure, and assessment endpoint response along with the rationale for their selection

. For halosulfuron

methyl , the following ecological risk hypothesis will be employed for the national

- level ecological risk assessment:

Given the uses of halosulfuron

- methyl and its environmental fate properties, there is a likelihood of exposure to non

- target terrestrial and aquatic plants

. When used in accordance with the label, halo sulfuron

- methyl may result in potential adverse effects upon the survival, growth, and reproduction of non

- target terrestrial and aquatic plants

.

6.2

. Conceptual Diagram

The conceptual model used to depict the potential ecological risk associated with the use of halo sulfuron

- methyl (the stressor) assumes that as a pesticide, halo sulfuron

- methyl can adversely affect terrestrial and aquatic organisms (the receptors) if environmental concentrations exceed toxic thresholds as a result of application according to the label directions ( Figure s 3 and 4 )

. Ecological receptors that may potentially be exposed to halo sulfuron

- methyl include : terrestrial and semi

- aquatic wildlife ( such as mammals, birds, terrestrial

- phase amphibians and reptiles) ; terrestrial and semi

- aquatic pla nts ; and terrestrial invertebrates

. Additionally, given the mobility of halo sulfuron

- methyl , aquatic organisms (freshwater and estuarine/marine fish and invertebrates, aquatic

- phase amphibians, and aquatic plants) are potential receptors in adjacent
water bodies through off

- site transport of halo sulfuron

- methyl from the application site through runoff, erosion, and spray drift.- 30 of 75

- Figure 3

. Conceptual model for halo sulfuron

- methyl exposure to aquatic organisms

. Dashed lines indicate route of exposure considered of lower likelihood for halo sulfuron

- methyl

. 

### Stressor

Source

Receptors

Attribute Change Ground or Aerial Applications of Halosulfuron

- methyl

Spray drift

Fish/aquatic

- phase amphibians Eggs Larvae Juveniles / Adults

Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Habitat integrity Reduction in primary productivity Reduced cover Community change Su rface water Runoff

Aquatic Animals Invertebrates Vertebrates 

### Exposure Media

Uptake/gills or integument

Ingestion Ingestion A tmospheric transport

Wet/dry deposition Soil Ground water

Uptake/gills or integument

Aquatic Plants Non

- vascular Vascular Uptake/cell, roots, leaves Riparian plant terrestrial
exposure pathways see

Figure 2- 31 of 75

- Figure 4

. Conceptual model for halo sulfuron

- methyl exposure to terrestrial organisms

. Dashed lines indicate route of exposure considered of lower importance for halo sulfuron

- methyl

.

7

. Analysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment will be estimated

. The use, environmental fate, and ecological effects of halo sulfuron

- methyl will be characterized and integrated to assess the r isks

. This will be accomplished using a risk quotient (ratio of exposure concentration to effects concentration) 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 and/or magnitude of an adverse effect

. However, as outlined in the Overview Document (USEPA 2004), the likelihood of effects to individual organisms from particular uses of halo sulfuron

- methyl may be estimated using the probit dose

- response slope and either the level

- of

- concern (discussed below) or the 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 halo sulfuron

- methyl

. 

### Stressor

Source

Receptors

Attribute Change Applications of Halosulfuron

- methyl

Direct application Spray drift

Birds / Terrestrial

phase amphibians / reptiles / mammals/ Insect s il Terrestrial

i nver ts

Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in
prey Habitat integrity Reduction in primary productivity Reduced cover Community change Terrestrial/riparian plants grasses/forbs, fruit, seeds (trees, shrubs) Runoff

Mammals 

### Exposure Media Soil

Ingestion Ingestion

Ingestion Ingestion Dermal uptake/Ingestion A tmospheric transport

Root uptake Wet/dry deposition

Birds / Amphibians

Ingestion- 32 of 75

- 7.1

. Stressors of Concern

The stressor of concern in the assessment is the parent compound halosulfuron

- methyl

. Cleavage of the sulfonylurea bridge (

- NH

- CO

- NH

- SO2

- ) between the two ring structures in the parent compound is predicted to result in degradates that are either not phytotoxic or require relatively higher residues to affect plant growth. Therefore, the long

- term phytotoxicity of halosulfuron

- methyl observed under some field conditions is likely due to the very high persistence of the parent compound.

Terrestrial exposure Exposures in terrestrial habitats will model the parent compound alone due to its high persistence and limitations in the models to incorporate the fate of the degradate s

. Aquatic exposure The metabolite desmethyl halosulfuron (CP 147922) retains the sulfonylurea bridge and could potentially contribute to the overall total toxic residues for aquatic exp osure . However, based upon currently available fate information, desmethyl halosulfuron does not contribute significantly to the environmental exposure in aquatic environments. This conclusion may be modified, depending on the results of the additional fat e studies that are requested in this problem formulation.

In addition, the halosulfuron rearrangement ester (CP 147925 or CP 151790) contains a contracted sulfonylurea bridge. However, this compound is predicted to be substantially less toxic than the par ent compound to aquatic taxa (see Appendix C ). Therefore, the halosulfuron rearrangement ester will not be included as a stressor of concern.

Based on these lines of evidence, e valuation of parent compound alone is expected to accurately represent the pot ential aquatic exposure that may result in risk concerns following halosulfuron

methyl application.

Residues from application of multiple sulfonylurea active ingredients Additionally it should be noted that the aminopyrimidine degradate of halosulfuron methyl is identical to fractional degradates of several other sulfonylurea herbicides such as amidosulfuron, bensulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron, formasulfuron, imazosulfuron, mesosulfuron, nicosulfuron, o rthosulfamuron, pyrazosulf uron, rimsulfuron, sulfometuron

methyl, sulf osulfuron, and trifloxysulfuron. Available evidence from environmental fate guideline studies submitted to the Agency for halosulfuron methyl shows that this metabolite can be quite persistent in the environment. To the extent that multiple sulfonylureas with the aminopyrimidine moiety p resent may be included in the same regions the level of exposure to this metabolite may be increased beyond the level anticipated for this individual chemical
assessment

.- 33 of 75

- In some cases halosulfuron methyl is applied with other herbicides and exposure to m ultiple active ingredients at the same time might occur. There are several products of specific mixtures of halosulfuron

- methyl and other herbicides:

**•** Yukon: a mixture with dicamba.

**•** Permit Plus: a mixture with thifensulfuron

- methyl.

**•** Priority: a mixture wit h carfenthrazone

- ethyl

**•** RiceEdge (Registration # 71085

- 31 and

- 32) with propanil (used on rice; fields may be flooded; rate for halosulfuron methyl is only 0.0465 lb ai and 0.062 lb ai / acre / season)

**•** NC

- 398: a mixture with dicamba.

**•** Gwn

- 9889: a mixture wi th tribenuron methyl and metribuzin

In its ecological risk assessments, the Agency does not routinely include an eva luation of mixtures of active ingredients, either those mixtures of multiple active ingredients in product formulations or those in the app licator’s tank

. In the case of registered product formulations of multiple active ingredients

, each active ingredient is subject to an individual risk assessment for regulatory decision regarding the active ingredient on a particular use site

. If effects data are available for a formulated product containing more than one active ingredient, the data may be used qualitatively or quantitatively in accordance with the Agency’s Overview Document and the Services’ Evaluation Memorandum (USEPA, 2004; Williams and Hogarth, 2004)

.

7.2

. Measures of Exposure

In order to estimate risks of halosulfuron

- methyl exposures in aquatic and terrestrial environments, exposure modeling will be based on ap plication rates and methods cited in Table 1

. Measures of exposure are based on aquatic and terrestrial models that predict estimated environmental concentrations (EECs) of halosulfuron

- methyl. For the rice use, the Tier I Rice Model is used to assess ecological exposure in surface water from relea sed paddy water following use on rice (for drinking water exposure in human dietary exposure risk assessments a model is currently in development and may or may not be approved for use in time for Registration Review). For other uses it might be necessary to complete an aquatic ecological risk assessment of halosulfuron including the following:

Environmental concentrations will be modeled using PRZM

- EXAMS. When there are multiple crop use scenarios for halosulfuron modeling using PRZM

- EXAMS, EFED will ch oose conservative surrogate scenarios that are likely to generate high

- end EECs. In addition, the potential for contaminated irrigation water to adversely affect sensitive agricultural crops will be assessed.

Exposure estimates for terrestrial organisms assumed to be in the target area or in an area exposed to off

- site deposition are derived using the T

- REX model (version 1.4.1, 10/09/2008). This model incorporates the Kenaga nomograph, as modified by Fletcher et al. (1994), which is based on a large set of field residue data. The upper limit values from the nomograph represent the upper bound of residue values from actual field measurements (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, including information on 118 species of plants, 121- 34 of 75

- pesticides, and 17 chemical classes. Based on these data, T

- REX assumes a 35

- day foliar dissipation half

- l ife in the absence of other data.

The model used to derive EECs relevant to terrestrial plants is TerrPlant

. Since risks to terrestrial plants from spray drift of halosulfuron

- methyl , terrestrial plant exposure assessment is appropriately further refine d with the spray drift model AgDRIFT. These models are parameterized using relevant reviewed environmental fate data from registrant submissions and the literature

. Model input values will be consistent with the most recent version of the input parameter guidance (Version 2.1

, USEPA 2009).

The Environmental Fate and Effects Division (EFED) most recently conducted a drinking water assessment for soybeans and other previously registered uses in June 2009 (DP Barcode D358032 8 ). Estimated drinking water con centrations (EDWCs) for surface and ground water were derived from the EFED Tier 1 screening models, FIRST and SCI

- GROW, respectively. This document presented a Tier 1 drinking water assessment (DWA) which was prepared for the Health Effects Division (HED ). All previous drinking water assessments have resulted in estimated drinking water concentrations (EDWCs) which were below the HED level of concern (LOC).

Two screening tools were utilized to assess the potential for halosulfuron

- methyl exposure to
te rrestrial organisms via inhalation and drinking water exposure. The S creening T ool for I nhalation R isk (STIR v.1.0) was used to calculate an upper bound estimate of exposure using vapor pressure and molecular weight of halosulfuron

- methyl for vapor phase exposure, as well as the maximum application rate and method of application for spray drift. The scree ning analysis considers results from several toxicity studies including acute oral and inhalation rat toxicity (oral LD 50 = 3170 mg/kg bw and LC 50 >4.8 mg/L, respectively) as well as the most sensitive acute oral avian toxicity endpoint (bobwhite quail, LD 50 > 2210 mg ai/kg bw). Based on the results of the STIR model, inhalation exposure alone was determined not to be a potential pathway of concern for avian and mammalian species on an acute basis.

The S creening I mbibition P rogram (SIP v.1.0) was used t o calculate an upper bound estimate of exposure using halosulfuron

- methyl’s range of solubility in water (15 mg/L at pH 5, 1650 mg/L at pH 7 and 7470 mg/L at pH 9), the most sensitive acute oral and chronic avian toxicity endpoints ( LD 50 > 2210 mg ai/kg b w and NOAEL = 1010 mg a.i./diet , respectively ) and the most sensitive acute and chronic mammalian toxicity endpoints ( oral LD 50 = 3170 mg/kg bw and NOAEL = 50 mg a.i./kg/day, respectively). At pH 5, drinking water exposure of halosulfuron

methyl is not ex pected to be a concern for birds and mammals. However, drinking water exposure was determined to be a potential pathway of concern for avian and mammalian species on an acute basis and chronic basis within the range of solubility for halosulfuron

- methyl a t pH 7 and 9. Based on the results of the SIP screen, drinking water theoretically cannot be ruled out as a potential route of exposure to birds and mammals, based solely on the solubility of the chemical.

8 Halosulfuron methyl Drinking Water Assessment for Additional food uses (including proposed use on soybean) ; 6/4/2009.- 35 of 75

- To further explore the potential for drinking water e xposure to birds and mammals, a conservative exposure scenario was created that incorporates the application rate of the chemical. The maximum registered applicat ion rate of halosulfuron

- methyl ( 0.94 lbs a.i./A ) was assumed to be applied directly to a puddle with 2.54 cm d epth (1 inch), 1 meter width and 1 meter length (area = 1 m 2 , volume = 0.0254 m 3 ) . Based on these assumptions, direct application to water would only result in a halosulfuron

- methyl concentration of 0.41 mg a.i./L (0.94 lbs a.i./A = 10.5 mg/m 2 , assuming the hypothetical dimensions of a small puddle, 0.0254 m 3 or 25.4 L ).

In comparison, SIP was used to estimate the level of exposure that may result in drinking water concerns for birds and mammals. The chemical concentrations in SIP are represented by the solubility of the chemical in the tool, a s one assump tion for the screen is that the chemical is present at its solubility limit in water. Based on the avian and mammalian toxicity endpoints for halosulfuron

- methyl, a concentration of 62 mg a.i./L would need to be achieved before chronic drinking water concerns occur for avian species . Chronic concerns to birds are indicated at a lower level than either acute risk concer ns to birds and mammals or chronic risk concerns to mammals , based on the toxicity endpoints for the chemical and the water intake rates for each taxon. Therefore, upon further analysis, the drinking water exposure pathway to birds and mammals is not likely result in risk concerns

, due to the low application rate of the chemical in relation to the concentration that would need to be achieved before drinking water would b e a concern. In addition, the acute estimates provided in the screen likely overestimate the likelihood of importance of the drinking water pathway on an acute basis, as the acute toxicity values are based on the highest halosulfuron

- methyl treatment conce ntration in the submitted avian and mammalian acute oral tests, at which no mortality occurred.

The analysis of the individual dietary, inhalation and drinking water routes of exposure in these screening level tools does not consider that aggregation with other exposure pathways. However, the Agency does consider the relative importance of other routes of exposure in situations where data indicate that pesticide exposures through other routes may be potentially significant contributors to wildlife risk (U S EPA, 2004). More information about the models and tools used for pesticide ecological risk assessments can be found on the EPA’s website at http://www.epa.gov/pesticides/ science/models_pg.htm#terrestrial

. Although not available at this time, t he Agency is actively pursuing modeling techniques to account for dermal exposure via direct application of spray and by incidental contact with contaminated vegetation, soil and wat er.
Exposure concentrations for terrestrial plants are derived using TerrPlant (v

. 1.2.2)

. This model uses estimates of pesticides in runoff and in spray drift to calculate EECs

. EECs are based upon solubility, application rate and minimum incorporation depth

. The AgDRIFT (v2.01; May 2001) or AgD ISP (v

. 8.15) spray drift model may be used to assess exposures of organisms to halo sulfuron

- methyl deposited on terrestrial habitats by spray drift

.- 36 of 75

- 7.3

. Measures of Effect

Ecological effects data are used as measures of direct and indirect effects to biological receptors. Data are typically obtained from registrant

- submitted studies or from literature studies identified by ECOTOX. The ECOTOX database provides more ecological effects data in an attempt to bridge existing data gaps. ECOTOX is a source for locating single chemical toxicity data and potential chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by the USEPA, Office of Researc h and Development, and the National Health and Environmental Effects Research Laboratory's Mid

- Continent Ecology Division.

The acute measures of effect 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 death of 50% of the test organisms. LC stands for “Lethal Concentration” and LC 50 is the concentration of a chemical that is estimated to kill 50% of the test organisms. EC s tands for “Effective Concentration” and the EC 50 is the concentration of a chemical that is estimated to produce a specific effect in 50% of the test organisms. Endpoints for chronic measures of exposure for listed and non

- listed animals are the NOAEL/NOA EC and NOEC. NOAEL stands for “No Observed

- Adverse

- Effect

- Level” and refers to the highest tested dose of a substance that has been reported to have no harmful (adverse) effects on test organisms. The NOAEC ( i.e. , “No

- Observed

- Adverse

- Effect

- Concentratio n”) is the highest test concentration at which none of the observed effects were statistically different from the control. For non

- listed plants, only acute exposures 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.

At the time of the risk assessment, updated i nformation on the potential effects of halosulfuron

methyl to non

- target organisms will be collected from the Ecological Incident Inform ation System (EIIS)

, Aggregrate Incident Reports and the Avian Monit oring Information System (AIMS)

.
Where available, sub

- lethal effects observed in both registrant

- submitted and open literature studies will be evaluated qualitatively. Such effects may include behavioral changes ( e.g. , lethargy and changes in coloration). Quantitative assessments of risks, though, are limited to those endpoints that can be directly linked to the Agency’s assessment endpoints of impaired survival, growth and reproductio n.

In the absence of taxon

- specific data, t he assessment of risk for direct effects to non

- target organisms makes the assumption that toxicity of halo sulfuron

- methyl to birds is similar to terrestrial

- phase amphibians and reptiles

. The same assumption is made for fish and aquatic

phase amphibians

. In the absence of data for either acute or chronic effects, the conservative assumption will be to presume that halo sulfuron

- methyl is toxic

.

7.4

. Integration of Exposure and Effects- 37 of 75

- Risk characterization is the integration of exposure and ecological effects characterization to determine the potential ecological risk from the registered uses of halo sulfuron

- methyl and the likelihood of direct and indirect effects to non

- target organism s in aquatic and terrestrial habitats

. The exposure and toxicity effects data are integrated in order to evaluate the risks of adverse ecological effects on non

- target species

. For the assessment of halo sulfuron

- methyl risks, the risk quotient (RQ) metho d 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)

. These criteria are used to indicate when halo sul furon

- methyl use, as directed on the labels, has the potential to cause adverse direct or indirect effects to non

- target organisms

. In additi on, halosulfuron

- methyl incident data 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

. An effort will be made to further qualitatively describe risk using probabilistic tools that the Agency has developed

. These tools have been reviewed by FIFRA Scientific Advisory Panels and have been deemed as appropriate means of refining assessments where deterministic approaches have identified risks ( http://www.epa.gov/scipoly/sap/index.htm )

. Newer 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 the Federal Food, Drug, and Cosmetic Act (FFDCA) , EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, includin g assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, org an weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss , and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration 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 section 408(p), halosulfuron

- methyl is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determ ine whether certain substances, including pestici de activ e and other ingredients, may have an effect in humans or wildlife simi lar to an effect produced by

a naturally occurring estrogen, or other such endocrine effects as t he Administrator may designate. The EDSP employs a two

- tiered approach to making the sta tutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal- 38 of 75

- systems. Chemicals that go through Tier 1 scr eening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is desi gned to identify any adverse endocrine

- related effects 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 Oc tober 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Halosulfuron

methyl is not among the group of 58 pesticide active ingredients o n the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

- ins, requiring the submission of EDSP screening assays for halosulfuron

- methyl

. For further information on the stat us of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening 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 threatened and/or endangered (listed) species from registered uses of halo sulfuron

- methyl

. This assessment w ill be conducted i n accordance with the Overview Document (USEPA 2004), provisions of the ESA, and the Services’ Endangered Species Consultation Handbook (USFWS/NMFS, 1998).

The assessment of effects associated with the registration of halo sulfuron

- methyl is based on an action area

. The action area is considered to be the area directly or indirectly affected by the federal action, as indicated by the exceedance of Agency Levels of Concern (LOCs) used to evaluate direct or indirect effects

. The Agency’s app roach to defining the action area under the provisions of the Overview Document (USEPA 2004) considers the results of the risk assessment process to establish boundaries for that action area with the understanding that exposures below the Agency’s defined LOCs constitute a no

- effect threshold

. For the purposes of this assessment, attention will be focused on the footprint of the action (the area where halo sulfuron

- methyl application occurs), plus all areas where offsite transport (spray drift, runoff, etc .) may result in potential exposure that exceeds the Agency’s LOCs

. Specific measure s of ecological effect that define the action area for listed species include any direct and indirect effects and/or potential modification of its critical habitat, including reduction in survival, growth, and reproduction as well as the full suite of sublethal effects available in the effects literature

. Therefore, the action area extends to a point where environmental exposures are below any measured lethal or sublethal effect threshold for any biological entity at the whole organism, organ, tissue, and cellular level of organization

. In situations where it is not possible to determine the threshold for an observed effect, the action area will initially be assumed to incl ude all counties where halo sulfuron

- methyl is used in the United States.- 39 of 75

- 7.8

. Drinking Water Assessment

A drinking water assessment will be conducted to support future human health risk assessments of halosulfuron methyl should it be required, based on all the available environmental fate information. The drinking water assessment will incorporate model estimates of halosulfuron methyl in surface and ground waters. Concentrations in surface waters will be estimated using FQPA Index Reservoir Screening T ool (FIRST, v.1.1.1, 12/18/07) (or subsequently using PRZM/ EXAMS, with the Index Reservoir

– for description see above

– if refinements are required). Ground water estimates of concentrations will be obtained using the Screening Concentration In GRound W ater (SCI

- GROW) model (v.2.3, July 2003). The drinking water assessment will also include a summary of available surface and ground water monitoring data.

7.9. Environmental Monitoring Data

Halosulfuron

- methyl has not been included in the United States Geological Survey’s (USGS) National Water Quality Assessment Program (NAWQA) list of analytes nor was it included in the pilot reservoir monitoring study conducted by USGS with EPA Support ( USGS Open file report 01

- 456 ). The most extensive study of halo sulfuron

- methyl residues in surface water from Battaglin et al. (1999, 2000) 9 who screened reservoir, river, and ground water samples for a variety of low

- rate herbicides, including halosulfuron. Out of 129 water samples from Midwestern streams and river s, halosulfuron was detected in 7 samples at concentrations above 0.01 ug/L (ppb), with a maximum concentration of 0.067 ppb. No sampling for halosulfuron was reported in the 1992 Pesticides in Ground Water Database (Jacoby et al., 1992) 10

. Previously, a prospective Ground

- Water Monitoring Study (see EFED Review of DP Barcode D226451 dated 2/14/97) was requested, but that requirement has been deferred by the Agency.

During the risk assessment process, the following databases and sources will be searched for moni toring information on halosulfuron :

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

9 Battaglin, W.A., Furlong, E.T., Burkhardt, M.R., and Peter, J.C. 1999. Occurrence of Sulfonylurea, Sulfonamide, Imidazolinone, and other herbicides in Midwestern rivers, reservoirs, and ground water, 1998 in U.S. Geological Survey Toxic Substan ces Hydrology Program

-- Proceedings of the Technical Meeting, Charleston, South Carolina, March 8

- 12, 1999: U.S. Geological Survey Water

- Resources Investigations Report 99

- 4018B, Volume 2, pp. 215

- 225.

Battaglin, W.A., Furlong, E.T., Burkhardt, M.R., an d Peter, J.C. 2000. Occurrence of Sulfonylurea, Sulfonamide, Imidazolinone, and other herbicides in rivers, reservoirs, and ground water in the Midwestern United States, 1998. Science Total Environ. Vol. 248, Issues 2

- 3, 5 April 2000, Pages 123

- 133.

10 Jacoby, H.J. et al. U.S. EPA. 1992. Pesticides in Ground Water Database

- A Compilation of Monitoring Studies: 1971

- 199, EPA 734

- 12

- 92

- 001.- 40 of 75

- **•** The United States Geological Survey (USGS) Nati onal Water

- Quality Assessment (NAWQA) Program Data Warehouse ( http://infotrek.er.usgs.gov/traverse/f?p=NAWQA:HOME:1405517206944567 )

**•** The USGS National Stream Quality Account ing Network (NASQAN) program (http://water.usgs.gov/nasqan/)

**•** Sampling for Pesticides Residues in California Well Water Cumulative Report; EEH03

- 08; December 2003 (http://www.cdpr.ca.gov/docs/emon/pubs/ehapreps/eh0308.pdf)

**•** California Department of Pesticid e Regulation (DPR) Surface Water Database ( http://www.cdpr.ca.gov/docs/emon/surfwtr/surfdata.htm )

8.0

. Preliminary Identification of Data Gaps

8.1

. Environmental Fate

The studies submitted to fulfill environmental fate data requirements for halosulfuron

- methyl are not complete by current standards. The requirements have not been met as stipulated in 40 CFR part 158 Subpart N §158.1300 for all pesticides with use pattern s for aquatic food and nonfood applications:

**•** Guideline 835.4100

. There are acceptable data from only two sites for aerobic soil metabolism. The guideline stipulates that results from at least four relevant soils of different organic carbon content, pH , clay content, and microbial biomass must be submitted in order to characterize the variability in the aerobic biodegradation of halo sulfuron

- methyl in the environment. Due to the high variability in halosulfuron

- methyl persistence by site additional tes ts will also be required (see below.)

**•** Guideline 835.2120

. The submitted hydrolysis study is acceptable; but given the apparent critical importance of the change in hydrolysis rate of halosulfuron

methyl with pH and temperature, an additional study will be required. Suggested parameters include testing at pH 5, 7, and 9 and at 10, 15, 20, and 25 C for 6 0 days (and additionaly at pH 4, 6 and 8 at 1 5 C) and analysis for halosulfuron

methyl and potent ially major hydrolysis products.

**•** Non

- Guideline Study. Environmental Chemistry Analytic Methods (ECMs)/Independent Laboratory Validation (ILV). ECMs in soil and water and ILVs used in halosulfuron environmental fate studies are requested at this time. Environmental chemistry methods for analysis of halosulfuron methyl and its major degradates in soil and water were su bmitted as part of the aquatic field dissipat ion study (MRID 444373

- 04) but no ILVs have been submitted to the Agency. Therefore, ECMs should be resubmitted and ILVs should be conducted for parent halosulfuron and its major degradates in water and soil.

For the 835.4100 additional tests, prior to providing complete guideline studies in at least 2 additional soils, the registrant shall conduct limited studies for parent decline (analysis for degradate formation in these preliminary studies is optional) for at least ten soil types representative of the spectrum of major halosulfuron

- methyl use areas. Particular attention- 41 of 75

- should be paid to selecting representative low pH soils and a variety of organic matter amounts and type and mineral compositions should be included in the selected test soils. These preliminary studies should be conducted with sampling and analysis out to 180 days after application or until parent halosulfuron

- methyl has declined below 1% of the applied amount (whichever comes first). The ob jective of the preliminary studies is to provide a baseline for the range of metabolism rates likely to occur in the field for halosulfuron

- methyl; the registrant may choose to also choose at least two of the soils where halosulfuron

- methyl was most persis tent to conduct the required two addition guideline 835.4100 studies (which require full characterization of the formation and decline of major degradates.) Note, as previously described the preliminary studies are needed because discrepancies between fiel d and laboratory results confirm that halosulfuron can be significantly more persistent at some sites than shown in the currently available aerobic soil metabolism studies.

Table 9 identifies studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment ( i.e. , whether there is a data gap).

Table 9. Summary of available environmental fate data.

Guideline Study Title MRID / ACC No. Classificat ion Data Gap? Comments

835.2120 Hydrolysis 42139409

, 42846801 Acceptable No

835.2240 Photodegradatio n in Water 42661409 Supplemental No

835.2410 Photodegradatio n on Soil 42661410 Supplemental No

835.4100 Aerobic Soil Metabolism 42139410, 42846802 Supplemental Yes Submitted studies in two soils are acceptable but tests in additional soils are required.

835.4200 Anaerobic Soil Metabolism None Not required No

835.4300 Aerobic Aquatic Metabolism 45671701 Not reviewed TD Review of this study is in progress.

835.4400 Anaerobic Aquatic Metabolism 42661411 Acceptable No

835.1240, 835.1230 Mobility

- Adsorption / Desorption 42139411 Acceptable No Also includes study with degradates.

835.6100 Terrestrial Field Dissipation 1 42661412 42661413 42661414 42976302 42976303 42976304 43699801 Acceptable No 42976303 and 42661414 are “pipe lysimeter” studies.- 42 of 75

- Guideline Study Title MRID / ACC No. Classificat ion Data Gap? Comments

835.6200 Aquatic Field Dissipation 44437304 1 Conditionally acceptable TBD Acceptance was made conditional upon submission of an acceptable aerobic aquatic metabolism study.

850.1730 Fish Accumulation NA Not required Halosulfuron

- methyl is not expected to bio

accumulate.

1

8.2

. Ecological Effects

Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are availabl e as addenda to the guideline for this test requirement.

The available ecological effects data for halo sulfuron

- methyl is incomplete. The full list of ecological toxicity data requirements and available studies are listed in Tables 10

- 12

. The following additional study is requested for halosulfuron :

**•** Terrestrial plant reproduction study (non

- guideline)

T errestrial plants are typically very sensitive to sulfonylurea urea herbicide exposure. There is evidence 11 to suggest plant reproduction may be affected by sulfonylurea herbicides at levels below effects on vegetative growth or visual injury (Fletcher et al ., 1993). Uncertainty regarding the potentially greater sensitivity of terrestrial plant reproduction ha s been discussed extensively in the environmental fate and effects R eregistration E ligibility D ecision assessment for chlorsulfuron (D330621). Therefore, to the extent that terrestrial plant reproduction is more sensitive to halo sulfuron

- methyl than growt h endpoints, risks to terrestrial plants may be underestimated in this risk assessment. Additional information on the reproductive toxicity of halo sulfuron

- methyl to terrestrial plants is necessary to address this uncertainty.

Note: The guideline numbers for terrestrial plants in the 40 CFR Part 158 were updated to reflect final 850 guidelines and do not reflect the numbers of the Public Draft 850 guidelines. Part 158 lists 850.4100 and 850.4150 (seedling emergence and vegetative vig or, respectively) for both Tier 1 and Tier 2 studies. The Public Draft guidelines 850.4100 and 850.4150 are for Tier 1 and 850.4225 and 850.4250 are for Tier 2.

**•** Non

- guideline. Terrestrial Plant Reproduction Study ( special study, see justification in App endix A ).

**•** Fish acute toxicity test, freshwater (850.1075)

– typical end

- use product

**•** Aquatic invertebrate acute toxicity test, freshwater daphnids (850.1010)

– typical end

- use product

11 Snipes et al. 1992, Bansal et al. 1999; Fletcher et al. 1993, 1995,1996; Bhatti et al. 1995; Al

- Khatib et al. 199 2; Boutin et al. 2000; Asghari and Evans 1992- 43 of 75

- TABLE 10

. Available ecological effects data for terrestrial animals exposed to halo sulfuron

- methyl

Guideline Description MRID Classification Study available ? Data requested ? Comments

850.2100 Avian oral toxicity 42139434 Acceptable Yes Yes Avian acute oral toxicity : Data are not available for passerine s pecies , which are required under 40 CFR Part 158. However, due to the low maximum expected exposure concentrations for avian species, as well as the low toxicity in the available acute oral study with bobwhite quail, no additional data are requested at this time. 850.2200 Avian dietary toxicity 42139435 Acceptable No No 42139436 Acceptable

850.2300 Avian reproduction 47792801 Acceptable No No 47792802 Acceptable

850.3020 Honeybee
acute contact toxicity 42139440 Acceptable No No

TABLE 11

. Available ecological effects data for aquatic animals exposed to halosulfuron

- methyl

.

Guideline Description MRID Classification Study available ? Data requested ? Comments

850.1075 Freshwater fish

– Acute toxicity 42661421 Acceptable

Yes Yes Freshwater fish acute toxicity and freshwater invertebrate acute toxicity : No information is available on the aquatic toxicity of a typical end

- use product containing halosulfuron methyl. Because halosulfuron

- methyl can be directly applied to water when used on ric e, more toxicity information on freshwater fish and invertebrates is requested for applicable products.

Saltwater fish acute toxicity : Solubility issues occurred in the submitted acute test with saltwater fish. However, due to the low expected aquatic exposure concentrations and low overall toxicity of halosulfuron

- methyl technical to aquatic organisms, no additional 42139438 Supplemental

42661422 Acceptable

42139437 Supplemental

850.1075 Saltwater fish

– Acute toxicity 42773001 Supplemental Yes No

850.1010 Freshwater invertebrates

– Acute toxicity 42139439 Acceptable Yes Yes

850.1025 850.1035 Saltwater invertebrates 42773002 Acceptable Yes No- 44 of 75

- Guideline Description MRID Classification Study available ? Data requested ? Comments

– Acute toxicity 42773003 Acceptable data are requested at this time.

Saltwater invertebrate life cycle test and saltwater fish early life stage test : No chronic studies have been submitted for estuarine/marine fish or invertebrates. For estuarine/marine chronic end points, acute

- to

- chronic ratios will be calculated in the absence of additional
taxa

- specific data. Based on the currently available information, saltwater organisms do not appear to have increased sensitivity to this chemical compared to the sensitivity o f freshwater organisms. 850.1300 Freshwater invertebrate

– life cycle
test 43493003 Acceptable

Yes No 43493002 Supplemental

850.1350 Saltwater invertebrates

– life cycle test None

--- No No

850.1400 Freshwater fish

– early life stage test 43493002 Acceptable Yes No

850.1400 Saltwater fish

– early life stage test None

--- No No- 45 of 75

- TABLE 12

. Available ecological effects data for plants exposed to halo sulfuron

- methyl

.

Guideline Description MRID Classification Study available ? Data requested ? C omments

850.4225 Terrestrial Plant toxicity: Tier II seedling
emergence 42661424 and 43195501 (addendum) Acceptable Yes No

850.4250 Terrestrial Plant toxicity: Tier II vegetative vigor 42661425 and 43195502 (addendum) Acceptable Yes No

850. 5400 Aquatic Plant Growth: algae 43330702 Acceptable

Yes No 43330703 Acceptable

43330704 Acceptable

43330705 Acceptable

850.4400 Aquatic Plant Growth: vascular plants 43330701 Acceptable Yes No

Non guideline Terrestrial Plant Reproduction Study None

--- No Yes Special study, see justification in

Appendix A- 46 of 75

- 9

. References

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger

. 1994

. Literature review and evaluation of the EPA food

- chain (Kenaga) nomogram, an instrument for estimating pesticide residues on plants. Environ. Tox. Chem. 13:1383

- 1391.

Hoerger, F., and E.E. Kenaga. 1972. Pesticide residues on plants: Correlation of representative data as a basis for estimation of their magnitude in the environment. In F. Coulston and F. Korte, eds ., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Th ieme Publ, Stuttgart, West Germany, pp. 9

- 28.

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. Endangered Species Consultation Handbook: Procedures for Conducting Consultation and Conference Activities Under S ection 7 of the Endangered Species Act. Final Draft. March 1998.

USEPA. 2007. Bradbury, S. Guidance for Tier I Estimation of Aqueous Pesticide Concentrations in Rice Paddies. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substance, Environmental Fate and Effects Division. Internal Memorandum. May 8, 2007.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Agency, Office of Preventio n, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

USEPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Research and Development , Washington , D.C. EPA/630/R

- 95/002F. April 1998. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759

Willis, G.H. and L.L. McDowell. 1987. Pesticide Persistence on Foliage in Reviews of Environmental Contamination and Toxicology. 100:23

- 73.



## S ubmitted Fate Studies

62

- 3 Analytical Method

MRID Citation Reference- 47 of 75

- 45473503 Comb, A. (2001) NC

- 398 WG: Method Validation: Lab Project Number: RD 1549: NAS/337: NAS337/012433. Unpublished study prepared by Huntingdon Life Sciences Ltd. 60 p. {OPPTS 830.1800}



### 161

- 1 Hydrolysis

MRID Citation Reference

42139409 Kesterson, A.; Lawrence, B.; Lawrence, L. (1991) Hydrolysis of ?carbon 14| MON 12000 at pH 5,7 and 9: Lab Project Number: MSL

- 11505: PTRL 1288: PTRL 454. Unpublished study prepared by PTRL East, Inc. 97 p.

42846801 Moran, S. (1993) Response to EPA Comme nts on the Hydrolysis of (carbon 14)

- MON 12000 at pH 5, 7 and 9: Lab Project Number: R. D. 1181. Unpublished study prepared by Monsanto Co. The Agriculture Group. 26 p.



### 161

- 2 Photodegradation

- water

MRID Citation Reference

42661409 Kesterson , A.; Lawrence, B. (1993) Solution Photolysis of (carbon 14)

- MON 12000 in Natural Sunlight: Lab Project Number: MSL 12097: 512: 1153. Unpublished study prepared by PTRL East, Inc. 151 p.



### 161

- 3 Photodegradation

- soil

MRID Citation Reference

42661410 Kesterson, A.; Lawrence, B. (1992) Soil Surface Photolysis of (carbon 14)

- MON 12000 in Natural Sunlight: Lab Project Number: MSL 12096: 561: 1153. Unpublished study prepared by PTRL East, Inc. 66 p.



### 162

- 1 Aerobic soil metabolism

MRID Citation Reference

42139410 Chott, K.; Mehrsheikh, M. (1991) Aerobic Soil Metabolism of MON 12000: Lab Project Number: MSL

- 10663: RD 1061. Unpublished study prepared by Monsanto Ag Co. 248 p.- 48 of 75

- 42846802 Mehrsheikh, M. (1993) Response to EPA Comments on the Aerobic Soil Metabolism of MON 12000: Lab Project Number: RD 1181. Unpublished study prepared by Monsanto Co. The Agriculture Group. 14 p.



### 162

- 3 Anaerobic aquatic metab.

MRID Citation Reference

42661411 Kesterson , A.; Lawrence, B.; Mobley, S.; et al. (1993) Anaerobic Aquatic Metabolism of (carbon 14)

- MON 12000: Lab Project Number: MSL 12568: 491: 1153. Unpublished study prepared by PTRL East, Inc. 141 p.



### 162

- 4 Aerobic aquatic metab.

MRID Citation Reference

45671701 Volkl, S. (2002) Aerobic Aquatic Metabolism of (Carbon

- 14)

- Halosulfuron

Methyl: Lab Project Number: RD 1579: 823555: 01

- 42

- M1. Unpublished study prepared by RCC Ltd. 164 p.



### 163

- 1 Leach/adsorp/desorption

MRID Citation Reference

42139411 Nadeau, R.; Sidhu, R. (1991) Adsorption/Desorption Studies of MON 12000 and Three Aerobic Soil Metabolites: Lab Project Number: MSL

- 11288: RD 1061. Unpublished study prepared by Monsanto Ag Co. 198 p.



### 164

- 1 Terrestrial field dissipation

MRID Citation Reference

42139412 Mehrsheikh, M.; Allan, J. (1991) Confined Rotational Crop Study of MON 12000: Quantitation, Characterization and Identification of MON 12000 and its Metabolites in Rotational Crops: Lab Project Number: MSL

- 11156: RD 1 061. Unpublished study prepared by Monsanto Ag Co. 230 p.

42661412 Beasley, R. (1993) Dissipation of MON 12000 and MON 12000 Metabolites in Field Soil: Lab Project Number: MSL 12356: 9200520: 12356. Unpublished study prepared by Harris Labs, Inc., Monsanto, and Stewart Agricultural Services, Inc. 660 p.- 49 of 75

- 42661413 Beasley , R. (1993) Dissipation of MON 12000 and MON 12000 Metabolites in Field Soil: Lab Project Number: MSL 12357: 6103

- 156: 90

- 42

- R

- 4. Unpublished study prepared by Hazleton Wisconsin, Inc., Monsanto, and Stewart Agricultural Research Services, Inc. 588 p.

42 661414 White, R.; Schlicher, M. (1993) Dissipation of Radiolabeled MON 12000 and MON 12000 Metabolites in Field Soil: Interim Report: Lab Project Number: MSL 12463: 91

- 42

- R

- 3: 1153. Unpublished study prepared by Hazleton Wisconsin, Inc., Monsanto, and Amer ican Agricultural Services, Inc. 635 p.

42661415 Beasley, R. (1993) Storage Stability of MON 12000 and its Metabolites in or on Soil: Interim Report: Lab Project Number: MSL 12358: 1153: 12358. Unpublished study prepared by Monsanto. 97 p.

42976302 Bea sley, R. (1993) Dissipation of MON 12000 and MON 12000 Metabolites in Field Soil: Lab Project Number: 12892: 90

- 42

- R

- 2: 9200520. Unpublished study prepared by Monsanto Co., the Agric. Group; Stewart Agric. Research Services, Inc.; and Harris Laboratories, Inc. 943 p.

42976303 White, R.; Schlicher, M. (1993) Dissipation of Radiolabeled MON 12000 and MON 12000 Metabolites in Field Soil: Lab Project Number: MSL 12891: HWI 6103

- 157: 0642

- 91

- 3. Unpublished study prepared by Monsanto Co., the Agric. Group; Hazl eton Wisconsin, Inc.; and American Agric. Services, Inc. 731 p.

42976304 Beasley, R. (1993) Dissipation on MON 12000 and MON 12000 Metabolites in Turf Soil: Lab Project Number: MSL 12893: 90

- 42

- R

- 4: HWI

- 6103

- 156. Unpublished study prepared by Monsanto Co ., the Agric. Group; Stewart Agric. Research Services, Inc.; Hazleton Wisconsin, Inc.; Harris Laboratories, Inc. 764
p.
43699801 Beasley, R. (1995) MON 12000 Soil Dissipation Study: Lab Project Number: MSL 14062: 93

- 42

- R

- 3: RD 1310. Unpublished study prepared by Monsanto Co. and American Agricultural Services, Inc. 554 p.

44408101 Mehrsheikh, M. (1997) Storage Stability of MON

- 120 00 and its Metabolites in Water: Lab Project Number: 91

- 42

- R

- 11: MSL

- 14354: 1382. Unpublished study prepared by Monsanto Company. 85 p.



### 164

- 2 Aquatic field dissipation

MRID Citation Reference

44437304 Allan, J. (1997) Aquatic Sediment Dissipation Study of MON 12000 in Rice: Lab Project Number: 96

- 42

- R

- 4: MSL

- 14689: RD 1388. Unpublished study prepared by Monsanto Co. 432 p.- 50 of 75

- 

### 840.1200 Spray drift field deposition

MRID Citation Reference

48421801 Wright, J. (2011) Drift Study for Halomax 75 (Halosulfuron

- methyl) in California Rice Country. Project Number: 11/PRA/ACETO/064. Unpublished study prepared by Helena R&D, LLC and Environmental Micro Analysts, Inc. 84 p.

165

- 4 Bioaccumulation in fish

No Studies Submitted.

165

- 5 Bioaccum

- aquatic non

- target

No Studies Submitted.

71

- 1 Avian Single Dose Oral Toxicity Submitted Ecological Effects Studies

MRID Citation Reference

42139434 Campbell, S.; Grimes, J.; Smith, G. (1991) MON 12000: An Acute Oral Toxicity Study with the Northern Bobwhite Quail: Lab Project Number: WL

- 90

- 153: 139

- 268: RD 1061. Unpublished study prepared by Wildlife International, Ltd. 24 p.

71

- 2 Avian Dietary Toxicity

MRID Citation Reference

42139435 Foster, J.; Driscoll, C.; Hoxter , K. et al. (1991) MON 12000: A Dietary LC50 Study with the Mallard Duck: Lab Project Number: WL

- 90

- 155: 139

- 267: RD 1061. Unpublished study prepared by Wild life International, Ltd. 21 p.- 51 of 75

- 42139436 Foster, J.; Driscoll, C.; Hoxter , K. et al. (1991) MON 12000: A Dietary Study with the Northern Bobwhite Quail: Lab Project Number: WL

- 90

- 154: 139

- 266: RD 1061. Unpublished study prepared by Wildlife International, Ltd. 21 p.

42396213 Schermes, S. (1992) Results of the Analyses of Avi an Diet Samples for MON 12000: Lab Project Number: MSL 10305: EHL 90065. Unpublished study prepared by Monsanto Co. 24 p.

850.2300 Avian reproduction test

MRID Citation Reference

47792801 Temple, D.; Martin, K.; Beavers, J.; et al. (2009) Halosulfuron: A Reproduction Study with the Northern Bobwhite: Final Report. Project Number: 334/117. Unpublished study prepared by Wildlife International, Ltd. 159 p.

47792802 Temple, D.; Martin, K.; Beavers, J.; et al. (2009) Halosulfuron: A Reproducti on Study with the Mallard: Final Report. Project Number: 334/118. Unpublished study prepared by Wildlife International, Ltd. 158 p.

72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

42139437 Murphy, D. ; Smith, G. (1991) MON 12000: A 96

- Hour Static Renewal Acute Toxicity Test with the Bluegill Sunfish (Lepomis

macro

- chirus): Lab Project Number: WL

- 90

- 550: WL 139A

- 118: RD 1061. Unpublished study prepared by Wildlife International, Ltd. 52 p.

42139438 M urphy, D.; Smith, G. (1991) MON 12000: A 96

- Hour Static Renewal Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss) Lab Project Number: WL

- 90

- 549: WL 139A

- 117: RD 1061. Unpublished study prepared by Wildlife International, Ltd. 52 p.

4266142 1 Holmes, C.; Swigert, J. (1993) A 96

- hour Flow

- through Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): MON 12000: Lab Project Number: WL

- 92

- 123: 139A

- 148: 1153. Unpublished study prepared by Wildlife International, Ltd. 46 p.

42661422 Holmes, C.; Swigert, J. (1993) A 96

- hour Flow

- through Acute- 52 of 75

- Toxicity Test with the Bluegill (Lepomis macrochirus): MON 12000: Lab Project Number: WL

- 92

- 124: 139A

- 147: 1153. Unpublished study prepared by Wildlife International, Ltd. 46 p.

42661423 Holm es, C.; Swigert, J. (1993) A 48

- hour Flow

- through Acute Toxicity Test with the Cladoceran (Daphnia magna): MON 12000: Lab Project Number: WL

- 92

- 125: 139A

- 146: 1153. Unpublished study prepared by Wildlife International, Ltd. 47 p.

72

- 2 Acute Toxicit y to Freshwater Invertebrates

MRID Citation Reference

42139439 Murphy, D.; Smith, G. (1991) MON 12000: A 48

- Hour Static Renewal Acute Toxicity Test with the Cladoceran (Daphnia magna): Lab Project Number: WL

- 90

- 551: WL 139A

- 119: RD 1061. Unpublished study prepared by Wildlife International, Ltd. 51 p.

72

- 3 Acute Toxicity to Estuarine/Marine Organisms

MRID Citation Reference

42773001 Swigert , J.; Smith, G. (1993) MON 12000: A 96 Hour Flow

Through Acute Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus): Lab Project Number: WL

- 92

- 16: 139A

142: RD 1170. Unpublished study prepared by Wildlife International Ltd. 40 p.

42773002 Sw igert, J.; Smith, G. (1993) MON 12000: A 96 Hour Flow

Through Acute Toxicity Test with the Saltwater Mysid (Mysidopsis bahia): Lab Project Number: WL

- 92

- 17: 139A

- 141B: RD 1170. Unpublished study prepared by Wildlife International Ltd. 41 p.

42773003 Swi gert, J.; Smith, G. (1993) MON 12000: A 96 Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica): Lab Project Number: WL

- 92

- 18: 139A

- 143: RD 1170. Unpublished study prepared by Wildlife International Ltd. 45 p.

72

- 4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

MRID Citation Reference- 53 of 75

- 43493001 Graves, W.; Mank, M.; Swigert , J. (1993) MON 12000: An Early Life

- stage Toxicity Test With the Rainbow Trout (Oncorhynchus mykiss): Lab Project Numbers: WL

- 92

- 132: 139A

- 150: RD 1288. Unpublished study prepared by Wildlife Int'l. Ltd. 89 p.

43493002 Zelinka, E.; Martin, K.; Swigert , J. (1993) MON 12000: A Flow

through Life

- Cycle Toxicity Test With the Cladoceran (Daphnia magna): Lab Project Numbers: WL

- 92

- 133: 139A

- 149A: RD 1288. Unpublished study prepared by Wildlife Int'l. Ltd. 56 p.

43493003 Zelinka, E.; Martin, K.; Swigert, J. (1993) MON 12000: A Flow

through Life

- Cycle Toxicity Test With the Cladoceran (Daphnia magna): Lab Project Numbers: WL

- 93

- 192: 139A

- 158: RD 1288. Unpublished study prepared by Wildlife Int'l. Ltd. 56 p.

123

- 1 Seed germination/seedling emergence and veg e tative vigor

MRID Citation Reference

42661424 Chetram , R. (1992) Tier 2 Seed Germination/Seedling Emergence Nontarget Phytotoxicity Study using MON 12000: Lab Project Number: MSL 12510: BL91

- 464: 1153. Unpublished study prepared by Pan Agricultural Labs, Inc. 314 p.

42661425 Chetram, R. (1992) Tier 2 Vege tative Vigor Nontarget Phytotoxicity Study using MON 12000: Lab Project Number: MSL 12511: BL91

- 463: 1153. Unpublished study prepared by Pan Agricultural Labs, Inc. 323 p.

43195501 Chetram, R. (1994) Tier 2 Seed Germination/Seedling Emergence NonTarget Phytotoxicity Study Using MON 12000: Addendum: Lab Project Number: MSL 13302: 93320: 1234. Unpublished study prepared by Pan

- Agricultural labs, Inc. 119 p.

43195502 Chetram, R. (1994) Tier 2 Vegetative Vigor Nontarget Phytotoxicity Study Using MON 12000 : Addendum: Lab Project Number: MSL 13301: 93314: 1234. Unpublished study prepared by Pan

- Agricultural Labs, Inc. 122 p.

123

- 2 Aquatic plant growth

MRID Citation Reference- 54 of 75

- 43330701 Thompson, S.; Swigert , J. (1994) MON 12000: A 14

- Day Toxicity Test with Duckweed (Lemna gibba G3): Lab Project Number: RD 1241: WL

- 93

- 149: 139A

- 156. Unpublished study prepared by Wildlife International Ltd. 48 p.

46004101 Sutherland, C.; Kendall, T.; Krueger, H. (2002) A 14

- Day Toxicity Test with Duckweed (Lemna gibba G3) with Subsequent Recovery Phase: MON 12000: Final Report. Project Number: WL/199/284, 139A/255A, R/D/1614. Unpublished study prepared by Wildlife International, Ltd. 81 p.

43330702 Thompson, S.; Swigert, J . (1993) MON 12000: A 5

- Day Toxicity Test with the Freshwater Algae (Selenastrum capricornutum): Lab Project Number: RD 1241: WL

- 92

- 178: 139A

- 151A. Unpublished study prepared by Wildlife International Ltd. 48 p.

43330703 Thompson, S.; Swigert , J. (1994) MON 12000: A 5

- Day Toxicity Test with the Freshwater Algae (Anabaena flos

- aquae): Lab Project Number: RD 1241: WL

- 93

- 274: 139A

- 164A. Unpublished study prepared by Wildlife International Ltd. 42 p.

43330704 Thompson, S.; Swigert, J. (1994) MO N 12000: A 5

- Day Toxicity Test with the Marine Diatom (Skeletonema costatum): Lab Project Number: RD 1241: WL

- 93

- 276: 139A

- 162. Unpublished study prepared by Wildlife International Ltd. 41 p.

43330705 Thompson, S.; Swigert, J. (1994) MON 12000: A 5

- Day Toxicity Test with the Freshwater Diatom (Navicula pelliculosa): Lab Project Number: RD 1241: WL

- 93

- 275: 139A

- 163. Unpublished study prepared by Wildlife International Ltd. 42 p.

141

- 1 Honey bee acute contact

MRID Citation Reference

42139440 Winter, P.; Hoxter, K.; Smith, G. (1990) MON 12000: An Acute Con

- tact Study with the Honey Bee: Lab Project Number: WL

- 90

- 183: 139

- 265: RD 1061. Unpublished study prepared by Wildlife Inter

- national Ltd. 17 p.- 55 of 75

- 

### Appendix A

. Justification for Special Stud ies
Guideline Number: none

Study Titles: Special Study for Non

- Target Plant Reproductive Toxicity Rationale for Requiring the Data As stated in the Problem Formulation, investigations/studies have indicated a small percentage of the label application rate of low dose high potency herbicides such as sulfonylureas, such as halosulfuron

- methyl, may impact the reproduction of non

- target t errestrial plants. However, there are no available data on adverse reproductive impacts to terrestrial plants from halosulfuron

- methyl residues due to spray drift. Terrestrial plant reproductive toxicity data would help to screen for potential plant risk s associated with halosulfuron

- methyl use. Plants form the basis of most habitats and contribute significantly to overall environmental quality. The loss of plant reproductive output could potentially have an adverse effect on animals, both invertebrates a nd vertebrates, as many are dependent on plant reproduction for a food source and for habitat quality and structure. A solid understanding of the potential risks to plants is therefore essential 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 reproductive risks to non

- target terrestrial plants, including the likelihood of potential risks to endangered species, either by direct effects or by indirect effects, and to reduce 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 mitigation is necessary. In the absence of this data, risks to terrestrial plants will b e presumed.

How could the data impact the Agency’s future decision

- making? These data, once submitted, should allow the Agency to characterize the risk posed to plant reproductive processes from halosulfuron

- methyl 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 assess the environmental risks the u se of halosulfuron

- methyl may pose. If the data indicate that halosulfuron

- methyl poses significant risks to these non

- target plant species, the Agency may explore additional decision options to minimize the risks to these species. The lack of these data will limit the flexibility the Agency and registrants have in complying with the Endangered Species Act and could result in use restrictions for halosulfuron

- methyl which may otherwise be avoided, or which are unnecessarily severe.- 56 of 75

- Guideline Number: 835.4100 (Enhanced Study Requested) Study Title: Aerobic Soil Metabolism Rationale for Requiring the Data Acceptable data on the aerobic soil metabolism of halosulfuron

- methyl in four soils are required under 40 CFR Part 158, Subpart N (revised July 1, 2009) for labeling that includes terrestrial uses. Submitted aerobic soil metabolism data were conducted at a n insufficient number of sites to meet current guidelines . The Agency has a limited understanding of how halosulfuron

- methyl behaves in aerobic soil environments once applied. There are acceptable data from only two sites for aerobic soil metabolism. The guideline specifically stipulates that results from at least four relevant soils of different organic carbon content, pH, clay content, and microbial biomass must be submitted in order to characterize the variability in the aerobic biodegradation of halosu lfuron

- methyl in the environment. Furthermore, d ue to the high variability in halosulfuron

- methyl persistence by site additional tests will also be required, as outlined below.

The behavior of parent halosulfuron methyl is highly variable from site to site, as evidenced by the variance in results regarding its persistence and mobility between laboratory and field data. Therefore, data above the minimum guidelines are being required under Guidelines 835.4100 and 835.2120 (rationale for the additional dat a requirements to supplement the minimum data requirements for the latter guideline is discussed separately).

For the 835.4100 additional tests, prior to providing complete guideline studies in at least 2 additional soils, the registrant shall conduct lim ited studies for parent decline (analysis for degradate formation in these preliminary studies is optional) for at least ten soil types representative of the spectrum of major halosulfuron

- methyl use areas (note, that the preliminary studies may track, but are not required to track the formulation and decline of degradation products). Particular attention should be paid to selecting a representative range of soil types / classifications representing a range of pH values and a variety of organic matter amoun ts and type and mineral compositions for the test soils. These preliminary studies should be conducted with sampling and analysis out to 180 days after application or until parent halosulfuron

- methyl has declined below 1% of the applied amount (whichever c omes first). The objective of the preliminary studies is to provide a baseline for the range of metabolism rates likely to occur in the field for halosulfuron

- methyl; the registrant may choose soils where halosulfuron

- methyl was most persistent to conduct at least the minimum required two addition guideline 835.4100 studies (which always require full characterization of the formation and decline of major degradates.) Note that the preliminary studies are needed because discrepancies between field and labora tory results confirm that halosulfuron can be significantly more persistent at some sites than shown in the currently available aerobic soil metabolism studies.- 57 of 75

- Practical Utility of the Data How will the data be used? The aerobic soil metabolism data from multiple soil types will facilitate a better understanding of the fate of halosulfuron

- methyl residues in soil. For example, if data indicate that degradation in aerobic conditions occurs rapidly in neutral and acidic soils to nontoxic transformation products, then the Agency could potentially determine that halosulfuron

- methyl residues of concern do not persist in these systems. The studies may potentially reveal that halosulfuron

- methyl degradation is relatively slow in certain types of soil systems which might justify certain restrictions on its use in these areas.

How could the data change the Agency ’s decision or impact the Agency’s future decision

making? In the absence of the requested data, halosulfuron

- methyl aerobic soil metabolism half

- lives will be conservatively assumed to be higher than shown in the limited available studies (which are not representative of all field conditions). If the required data indicate that halosulfuron

- methyl in aerobic soil envir onments is rapidly biodegraded to nontoxic degradation products, then risk assessment conclusions and associated labeled use precautions and/or restrictions could be made less restrictive.

Guideline Number: 835.2120 (Enhanced Study Requested) Study Tit le: Hydrolysis Rationale for Requiring the Data The submitted hydrolysis study is acceptable; but given the apparent critical importance of the change in hydrolysis rate of halosulfuron

- methyl with pH and temperature, an additional study will be required. Suggested parameters include testing at pH 5 , 7, and 9 and at 10, 15, 20, and 25 C for 6 0 days and analysis for halosulfuron

- methyl and potentially major hydrolysis products (with additional evaluations at pH 4, 6
, and 8 for the 1 5 C studies .)

Practical Utility of the Data How will the data be used? The hydrolysis rate data from multiple soil types will facilitate a better understanding of the fate of halosulfuron

- methyl residues in soil and water and more accurate predictions of surface and groundwater exposure.

How could the data change the Agency’s decision or impact the Agency’s future decision

making? In the absence of the requested data, halosulfuron

- methyl hydrolysis h alf

- lives will be conservatively assumed to be higher than shown in the limited available studies (which are not representative of all field conditions).- 58 of 75

- 

### Appendix B . Chemical structures of halosulfuron

- methyl and se lected environmental degradates

Halosulfuron

- methyl CHEMICAL NAME: methyl 5

- {[(dimethoxy

- 2

- pyrimidinyl) amino] carbonylaminosulfonyl

- 3

- chloro

- 1

- methyl

- 1

- H

- pyrazole

- 4

- carboxylate

Halosulfuron rearrangement ester or CP

- 151790 or PZ

- SP

- 2 CHEMICAL NAME: 3

- Chloro

- 5

- [(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]

- 1

- methyl

- 1H

- pyrazole

4

- carboxylic acid, methyl ester

1H

- Pyrazole

- 4

- carboxylic acid, 3

- chloro

- 5

- [(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]

- 1

- methyl, methyl ester OR

Methyl 3

- Chloro

- 5

- (4,6

- dimethoxypyrimidin

- 2

- ylamino)

- OR

1

- methylpyrazole

- 4

- carboxylate- 59 of 75

- Halosulfuron a minopyrimidine o r CP 17477 CHEMICAL NAME: 4,6

- Dimetho x y

- 2

- pyrimidinamine

Halosulfuron guanidine or PZ

- SP

- 12 IH

- Pyrazole

- 4

- carboxylic acid. S

- [([[( aminoiminomethyl)amino]carbonyl]amino]sulfonyl]

- 3

- chloro

- l

- melhyl

Halosulfuron acid or CP

- 147921 CHEMICAL NAME: 3

- Chloro

- 5

- [[[[(4,6

- dimethoxy

- 2

- pyrimidinyl) amino] carbonyl]amino] sulfonyl]

- l

- methyl

- 1H

pyrazole

- 4

- carboxylic acid- 60 of 75

- 3

- Chlorosulfonamide acid (pyrazole) or CP

- 147924 or PZ

- SP

- 8 CHEMICAL NAME: 5

- (Aminosulfonyl)

- 3

- chloro

- l

- methyl

- 1H

- pyrazole

- 4

- carbo x ylic acid

IH

- Pyrazole

- 4

- carboxylic acid. 5

- (aminosulfonyl)

- 3

- chloro

- l

- melhy l OR

Desmethyl halosulfuron or CP 147922 CHEMICAL NAME: 3

- Chloro

- 5

- [[[[(4

- hydroxy

- 6

- methoxy

- 2

- pyrimidinyl) amino] carbonyl] amino] sulfonyl]

- 1

- methyl

- 1H

- pyrazole

- 4

- carboxy!ic acid, methyl ester- 61 of 75

- 3

- Chlorosulfonamide ester or CP 147925 CHEMICAL NAME: 5

- (Aminosulfonyl )

- 3

- chloro

- l

- methyl

- 1H

- pyrazole

- 4

- carboxylic acid, methyl ester OR IH

- Pyrazole

- 4

- carboxylic acid. S

- (aminosulfonyl)

- 3

- chloro

- l

- melhyl

- . methyl es t er 

# S N H 2 

# O

O N N O O

C l- 62 of 75

- 

### Appendix C

. Aquatic Toxicity Predictions of Halosulfuron

- Methyl and Major Degradates from Structure

- Activity Relationships (SARs) using the ECOSAR Class Program and Review of Available Data

The structures of four halosulfuron methyl metabolites with demonstrated environmental persistence (as well as the parent molecule, for context) were entered into t he ECOSAR v.1.0 model as SMILES strings.

One of the major persistent metabolites of halosulfuron

- methyl, CP 17477 or 4,6

- Dimethoxy

- 2

- pyrimidinamine, is common to several other sulfonylurea pesticides with registrations in the US and/or other countries. This is the only metabolite of halosulfuron

- methyl with some measured toxicological data currently available. Both predicted and observed toxicological endpoint data for aquatic species are summarized in Tabl e C1 . CP17477 was classified as a neutral organic and an aromatic amine. Table C1 shows the observed values recorded in the Pesticide Properties database (PPDB) maintained by the FOOTPRINT Project 12 and predicted toxicity using either neutral organic or ar omatic amine structure

- activity relationships. Based on the data available in the PPDB database, the measured values are within the range of the predicted values by ECOSAR and more closely related to the toxicity values predicted for the neutral organic
st ructure

- activity relationship for this compound.

Table C1. Toxicity Data for Analog Chemical And QSAR Analysis for the aminopyrimidine metabolite of halosulfuron methyl (CP 17477). Endpoint CP 17477 (PPDB data 1 CP 17477 ) (ECOSAR

– aromatic amine SAR) CP 17477 (ECOSAR

– neutral organic SAR) Fish 96

- h LC 97 mg/L 50 (rainbow trout) 79 mg/L 920 mg/L

Fish chronic toxicity value No data
2 0.38 mg/L 90 mg/L

Algae 96h EC 50 120 mg/L ( P. subcapitata ) 9.2 mg/L 130 mg/L

Lemna 7

- d EC > 100 mg/L 50 No prediction No prediction Daphnid 48

- h EC > 100 mg/L 50 2.4 mg/L 469 mg/L Daphnid c hronic toxicity value 24 mg/L (21

- d NOEC)
2 0.05 mg/L 36 mg/L

1 Other company chemical codes for this metabolite include INJV0290, AE

- F092944, and HOE092944. Aquatic toxicity data were retrieved from PPDB through a search for the string “2

- amino

- 4,6

- dimethoxypyrimidine” or for “AE

- F092944” (duplicate entries for this compound in the database may not contain this information). The Pesticide Properties Database (aka. Footprint) may be accessed at: http://sitem.herts.ac.uk/aeru/footprint/en/index.htm
2 ChV = ECOSAR chronic toxicity va lue

12 More information accessible at: http://sitem.herts.ac.uk/aeru/footprint/

.- 63 of 75

- The ECOSAR results for the parent compound, halosulfuron

- methyl, and four degradates are presented below.

AMINOPYRIMINDINE ECOSAR OUTPUT:

Halosulfuron a minopyrimidine or CP 17477 CHEMICAL NAME: 4,6

- Dimetho x y

- 2

- pyrimidinamine


### SMILES: N1=C(C=C(OC)N=C1N)OC Molecular Weight 155.16

Molecular Formula C6 H9 N3 O2

SMILES : n1c(cc(OC)nc1N)OC CHEM : CAS Num: ChemID1: ChemID2: ChemID3: MOL FOR: C6 H9 N3 O2 MOL WT : 155.16 Log Kow: 0.95 (KowWin estimate) Melt Pt: Wat Sol: 1.108E+004 mg/L (WskowWin estimate)

ECOSAR v1.00 Class(es) Found

------------------------------ Anilines (Aromatic Amines) Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

========================= == ================== ======== ====== ========== Anilines (Aromatic Amines) : Fish 96

- hr LC50 78.845 Anilines (Aromatic Amines) : Fish 14

- day LC50 225.619 Anilines (Aromatic Amines) : Daphnid 48

- hr LC50 2.376 Anilines (Aromatic Amines) : Green Algae 96

- hr EC50 9.172 Anilines (Aromatic Amines) : Fish ChV 0.380 Anilines (Aromatic Amines) : Daphnid ChV 0. 050 Anilines (Aromatic Amines) : Green Algae ChV 6.078

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 922.143 (Baseline Toxicity ) : Daphnid 48

- hr LC50 468.756 : Green Algae 96

- hr EC50 131.427 : Fish ChV 89.591 : Daphnid ChV 35.968 : Green Algae ChV 39.276- 64 of 75

- Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect.

Anilines (Aromatic Amines):

-------------------------- For Fish Acute Toxicity Values: 2,3,5,6

- Tetrachloroaniline is 19 times more toxic than predicted by this SAR. Tetrabromoaniline may be more toxic than predicted by this SAR as well.

For Daphnid and Green Algae Toxicity Valu es: Tetrachloro

- and tetrabrom

aniline may be 20 times toxic than predicted by this SAR.

N

- Substituted anilines are less toxic than predicted by these SARs; for these compounds, Neutral Organic SARs are used.

ECOSAR v1.00 SAR Limitations:

---------- ------------------ Maximum LogKow: >7.8 (Fish 96

- hr LC50, Daphnid 48

- h LC50) Maximum LogKow: >3.7 (Fish 14

- day LC50) Maximum LogKow: >4 (Green Algae 96

- hr EC50 and ChV) Maximum LogKow: >4.3 (Fish ChV) Maximum LogKow: >2.4 (Daphnid ChV) Maximum Mol Wt: 1000

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

3

- Chlorosulfonamide ester or CP 147925 ECOSAR OUTPUT:

3

- Chlorosulfonamide ester or CP 147925 CHEMICAL NAME: 5

- (Aminosulfonyl)

- 3

- chloro

- l

- methyl

- 1H

- pyrazole

- 4

- carboxylic acid, methyl ester OR IH

- Pyrazole

- 4

- carboxylic acid. S

- (aminosulfonyl)

- 3

- chloro

- l

- mel hyl

- . methyl es t er NS(=O)(C1=C(C(OC)=O)C(Cl)=NN1C)=O

SMILES : NS(=O)(c1c(C(=O)(OC))c(CL)nn1C)=O CHEM : CAS Num: ChemID1: 

# S N H 2 

# O

O N N O O

C l- 65 of 75

- ChemID2: ChemID3: MOL FOR: C6 H8 CL1 N3 O4 S1 MOL WT : 253.66 Log Kow:

- 0.54 (KowWin estimate) Melt Pt: Wat Sol: 6.491E+00 4 mg/L (WskowWin estimate)

ECOSAR v1.00 Class(es) Found

------------------------------ Esters Amides Pyrazoles/Pyrroles Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Esters : Fish 96

- hr LC50 973.003 Esters : Fish 14

- day LC50 6. 3e+006 * Esters : Daphnid 48

- hr LC50 2773.907 Esters : Green Algae 96

- hr EC50 1553.011 Esters : Fish 32/33

- d ChV 160.932
Esters : Daphnid 21

- day ChV 3363.099 Esters : Green Algae ChV 171.468 Esters : Fish (SW) 96

- hr LC50 1886.022 Esters : Mysid Shrimp 96

- hr LC50 5335.749 Esters : Fish (SW) ChV 170.435 ! Esters : Mysid Shrimp (SW) ChV 8.13e+007 * Esters : Earthworm 14

- day LC5 0 21747.797

Amides : Fish 96

- hr LC50 3316.245 Amides : Daphnid 48

- hr LC50 777.645 Amides : Green Algae 96

- hr EC50 2.838 Amides : Fish ChV 19.604 Amides : Daphnid ChV 10.258 ! Amides : Green Algae ChV 0.424

Pyrazoles/Pyrroles : Fi sh 96

- hr LC50 44.265 Pyrazoles/Pyrroles : Daphnid 48

- hr LC50 26.196 Pyrazoles/Pyrroles : Fish ChV 4.280 ! Pyrazoles/Pyrroles : Daphnid ChV 2.814 !

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 27406.164 (Baseline Toxicity) : Daphnid 48

- hr LC50 11637.252 : Green Algae 96

- hr EC50 1771.492 : Fish ChV 2751.721 : Daphnid ChV 686.280 : Green Algae ChV 403.411

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect.

Note: ! = exclamation designates: The toxicity value was determined from a predicted SAR using established acute

- to

- chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual. When possible, this toxicity value should be considered in a weight of ev idence approach.

Esters:

------ For Fish LC50 (96

- h), Daphnid LC50, Mysid: If the log Kow is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.- 66 of 75

- For Fish LC50 (14

- d ay) and Earthworm LC50: If the log Kow is greater than 6.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the c ompound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50, Mysid LC50) Maxim um LogKow: 6.0 (Fish 14

- day LC50; Earthworm LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Amides :

------- No limitations known at this time.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maxim um LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV) Maximum Mol Wt: 1000

Pyrazoles/Pyrroles :

------------------- For Fish and Daphnid Acute Toxicity Values: If the log Kow of the chemical is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or i f the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and t he ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^- 67 of 75

- 3

- Chlorosulfonamide acid or CP 14792 4 ECOSAR OUTPUT:

3

- Chlorosulfonamide acid (pyrazole) or CP

- 147924 or PZ

- SP

- 8 CHEMICAL NAME: 5

- (Aminosulfonyl)

- 3

- chloro

- l

- methyl

- 1H

- pyrazole

- 4

- carbo x ylic acid

IH

- Pyrazole

- 4

- carboxylic acid. 5

- (aminosulfonyl)

- 3

- chloro

- l

- melhy l OR

SMILES: NS(=O)(C1=C(C(O)=O)C(Cl)=NN1C)=O

SMILES : NS(=O)(c1c(C(=O)(O))c(CL)nn1C)=O CHEM : CAS Num: ChemID1: ChemID2: ChemID3: MOL FOR: C5 H6 CL1 N3 O4 S1 MOL WT : 239.63 Log Kow:

- 0.49 (KowWin estimate) Melt Pt: Wat Sol: 7.083E+004 mg/L (WskowWin estimate)

ECOSAR v1.00 Class(es) Found

------------------------------ Amides

- acid Pyrazoles/Pyrroles

- acid Predict ed ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ==========

-- > Acid moeity found: Predicted values multiplied by 10

Amides

- acid : Fish 96

- hr LC50 28800.607 Amides

- acid : Daphnid 48

- hr LC50 6862.251 Amides

- acid : Green Algae 96

- hr EC50 26.026 Amides

- acid : Fish ChV 170.256 Amides

- acid : Daphnid ChV 90.525 ! Amides

- acid : Green Algae ChV 4.004

Pyrazoles/Pyrroles

- acid : Fish 96

- hr LC50 394.236 Pyrazol es/Pyrroles

- acid : Daphnid 48

- hr LC50 237.681 Pyrazoles/Pyrroles

- acid : Fish ChV 38.226 ! Pyrazoles/Pyrroles

- acid : Daphnid ChV 25.376 !

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 23661.834 (Baseline Toxicity) : Daphnid 48

- hr LC50 10103.599 : Green Algae 9 6

- hr EC50 1567.464 : Fish ChV 2373.346 : Daphnid ChV 600.724- 68 of 75

- : Green Algae ChV 359.97 3

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect.

Note: ! = exclamation designates: The toxicity value was determined from a predicted SAR using established acute

- to

- chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual. When possible, this toxicity value should be considered in a weight of evidence approach.

Amides :

------- No limitations known at this time.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV) Maximum Mol Wt: 1000

Pyrazoles/Pyrroles :

------------------- For Fish and Daphnid Acute Toxicity Values: If the log Kow of the che mical is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6 .4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is sol id and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^ Halosulfuron rearrangement ester ( CP

- 151790 CP 14792 4) ECOSAR OUTPUT:- 69 of 75

- Halosulfuron rearrangement ester or CP 147925 or CP

- 151790 or PZ

- SP

- 2 CHEMICAL NAME: 3

- Chloro

- 5

- [(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]

- 1

- methyl

- 1H

- pyrazole

- 4

- carboxylic acid,
met hyl ester

1H

- Pyrazole

- 4

- carboxylic acid, 3

- chloro

- 5

- [(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]

- 1

- methyl, methyl ester OR

Methyl 3

- Chloro

- 5

- (4,6

- dimethoxypyrimidin

- 2

- ylamino)

- 1

- methylpyrazole

- 4

- carboxylate OR

SMILES : COc1nc(Nc2c(C(=O)(OC))c(CL)nn2C)nc(OC)c1 CH EM : CAS Num: ChemID1: ChemID2: ChemID3: MOL FOR: C12 H14 CL1 N5 O4 MOL WT : 327.73 Log Kow: 2.01 (KowWin estimate) Melt Pt: Wat Sol: 162.1 mg/L (WskowWin estimate)

ECOSAR v1.00 Class(es) Found

------------------------------ Esters Pyrazoles/ Pyrroles Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Esters : Fish 96

- hr LC50 44.015 Esters : Fish 14

- day LC50 6252.322 * Esters : Daphnid 48

- hr LC50 90.360 Esters : Gree n Algae 96

- hr EC50 38.472 Esters : Fish 32/33

- d ChV 3.945 Esters : Daphnid 21

- day ChV 56.877 Esters : Green Algae ChV 9.727 Esters : Fish (SW) 96

- hr LC50 65.916 Esters : Mysid Shrimp 96

- hr LC50 63.179 Esters : Fish (SW) ChV 9.628 !
Este rs : Mysid Shrimp (SW) ChV 4650.664 * Esters : Earthworm 14

- day LC50 4243.429 *

Pyrazoles/Pyrroles : Fish 96

- hr LC50 2.220 Pyrazoles/Pyrroles : Daphnid 48

- hr LC50 3.655- 70 of 75

- Pyrazoles/Pyrroles : Fish ChV 0.252 ! Pyrazoles/Pyrroles : Daphnid ChV 0.280 !

=========================== ========= ========= ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 247.939 * (Baseline Toxicity) : Daphnid 48

- hr LC50 143.230 : Green Algae 96

- hr EC50 61.986 : Fish ChV 23.532 : Daphnid ChV 13.251 : Green Algae ChV 22.471

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect.

Note: ! = exclamation designates: The toxicity value was determined from a predicted SAR using established acute

- to

- chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual. When possible, this toxicity value should be considered in a weight of evidence approach.

Esters:

------ For Fish LC50 (96

- h), Daphnid LC50, Mysid: I f the log Kow is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.

For Fish LC50 (14

- day) and Earthworm LC50: If the log Kow is greater than 6.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the E C50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubili ty by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50, Mysid LC50) Maximum LogKow: 6.0 (Fish 14

- day LC50; Earthworm LC50) Maxim um LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Pyrazoles/Pyrroles :

------------------- For Fish and Daphnid Acute Toxicity Values: If the log Kow of the chemical is greater than 5.0, or if the compound is solid and th e LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the wate r solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

----------------------------- 71 of 75

- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Baseline Toxicity SAR Limi tations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000- 72 of 75

- PARENT HALOSULFURON METHYL ECOSAR OUTPUT:

Halosulfuron

- methyl CHEMICAL NAME: methyl 5

- {[(dimethoxy

- 2

- pyrimidinyl) amino] carbonylaminosulfonyl

- 3

- chloro

- 1

- methyl

- 1

- H

- pyrazole

- 4

- carboxylate Molecular Formula: 

### C 13 

### H 15 

### ClN 6 

### O 7 Smiles Code: 

### S

O=S(=O)(c1c(C(=O)OC)c(Cl)nn1C)NC(=O)Nc2nc(OC)cc(OC)n2

SMILES : O=S(=O)(c1c(C(=O) OC)c(CL)nn1C)NC(=O)Nc2nc(OC)cc(OC)n2 CHEM : CAS Num: ChemID1: ChemID2: ChemID3: MOL FOR: C13 H15 CL1 N6 O7 S1 MOL WT : 434.81 Log Kow: 0.40 (KowWin estimate) Melt Pt: Wat Sol: 15 mg/L (experimental database)

ECOSAR v1.00 Class(es) Found

------ ------------------------ Esters Amides Sulfonyl Ureas Pyrazoles/Pyrroles Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Esters : Fish 96

- hr LC50 486.273 * Esters : Fish 14

- day LC50 7.73e+005 *
Esters : Daphnid 48

- hr LC50 1228.641 * Esters : Green Algae 96

- hr EC50 621.988 * Esters : Fish 32/33

- d ChV 64.204 * Esters : Daphnid 21

- day ChV 1170.562 * Esters : Green Algae ChV 93.130 * Esters : Fish (SW) 96

- hr LC50 857.266 * Esters : Mysid Shrimp 96

- hr LC50 1629.007 * Esters : Fish (SW) ChV 92.429 *! Esters : Mysid Shrimp (SW) ChV 3.49e+006 * Esters : Earthworm 14

- day LC50 18603.76 0 *

Amides : Fish 96

- hr LC50 1033.179 * Amides : Daphnid 48

- hr LC50 334.777 * Amides : Green Algae 96

- hr EC50 2.668 Amides : Fish ChV 6.108 Amides : Daphnid ChV 4.416 ! Amides : Green Algae ChV 0.726- 73 of 75

- Sulfonyl Ureas : Daphnid 48

- hr LC50 1323.615 * Sulfonyl Ureas : Green Algae 96

- hr EC50 0.049 Sulfonyl Ureas : Daphnid ChV 118.392 *! Sulfonyl Ureas : Green Algae ChV 0.012 !

Pyrazoles/Pyrroles : Fish 96

- hr LC50 22.978 * Pyrazoles/Pyrroles : Daphnid 48

- hr LC50 19.809 * Pyrazoles/Pyrroles : Fish ChV 2.356 ! Pyrazoles/Pyrroles : Daphnid ChV 1.878 !

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 7578.789 * (Baseline Toxic ity) : Daphnid 48

- hr LC50 3603.776 * : Green Algae 96

- hr EC50 805.555 * : Fish ChV 745.362 * : Daphn id ChV 250.794 * : Green Algae ChV 217.647 *

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect.

Note: ! = exclama tion designates: The toxicity value was determined from a predicted SAR using established acute

- to

- chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual. When possible, this toxicit y value should be considered in a weight of evidence approach.

Esters:

------ For Fish LC50 (96

- h), Daphnid LC50, Mysid: If the log Kow is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects a t saturation are predicted.

For Fish LC50 (14

- day) and Earthworm LC50: If the log Kow is greater than 6.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxic ity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

----------------------- ----- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50, Mysid LC50) Maximum LogKow: 6.0 (Fish 14

- day LC50; Earthworm LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Amides :

------- No limitations known at th is time.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV) Maximum Mol Wt: 1000- 74 of 75

- Sulfonyl Ureas :

--------------- For Fish and Daphnid Acute Toxicity Values: If the log Kow of the chemical is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogK ow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Pyrazoles/Pyrroles :

------------------- For Fish and Daphnid Acute Toxicity Values: If the log Kow of the chemical is greater than 5.0, or if the compound is soli d and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

ECOSAR v1.00 SAR Limitations:

---------------------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000

Baseline Toxicity SAR Limi tations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV) Maximum Mol Wt: 1000- 75 of 75

-