Page 2 of 43

technical registrants in response to data requirements. This document provide s an overview of what is currently known regarding the environmental fate and ecological effects associated with imaz apic acid, its ammonium salt and its degradates and outline s uncertainties regarding attributes of the parent compound and its transformation products. It describes the preliminary ecological risk hypothesis and the processes that will be used during the completion of drinking water and ecological risk assessment s in support of Registration Review . This document also recommends studies that should be included in a data call

- in (DCI) to address uncertainties surrounding the environmental fate and potentia l ecological effects of imazapic

.

At least two uses of imaz apic (rangeland and Conservation Reserve program) are subject to prior ESA consultation by other Federal agencies (Bureau of Land Management and USDA). EPA will review any existing biological opinions ( BiOps ) at the time of risk assessment to determine whe ther any aspects of the consultation can inform the draft risk assessment for listed species.Page 3 of 43 

## Problem Formulation for the Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments

in Support of the Regist ration Review of Imazapic and its Ammonium Salt

PC Code: 129041 , 128943

CAS #: 104098

- 48

- 8 , 104098

- 49

- 9

Environmental Fate and Effects Division: Environmental Risk Branch V I Michael Wagman, Biologist Iwona L. Maher, Chemist

Reviewed by: Will iam Eckel, Ph.D., Senior Scien ce Advisor Amy Blankinship, Chemist Monica Wait

, Risk Assessment Process Leader Mark Corbin , Branch Chief U. S. Environmental Protection Agency Office of Pesticide Programs 1200 Pennsylvania Ave., NW Mail Code 7507P Washington , DC 20460Page 4 of 43 Table of Contents

1. Executive Summary

................................ ................................ ................................ ................. 5
2. Introduction

................................ ................................ ................................ ............................. 6 3. Use Characterization

................................ ................................ ................................ ................ 7 4. Conclusions from Previous Risk Assessments

................................ ................................ ........ 9 4.1 Ecological Risk and Drinking Water Assessments

................................ .......................... 9 4.2 Clean Water Act Programs

................................ ................................ ............................. 11 5. Environmental Fate and Transport

................................ ................................ ........................ 11
6. Receptors

................................ ................................ ................................ ............................... 16
7. Exposure Pathways of Concern

................................ ................................ ............................. 22 8. Analysis Plan

................................ ................................ ................................ ......................... 23 8.1 Stressors of Concern

................................ ................................ ................................ ....... 23 8.2 Measures of Exposure

................................ ................................ ................................ .... 23 8.3 Measures of Effect

................................ ................................ ................................ ......... 24
9. Endangered Species Assessment

................................ ................................ ........................... 24 10. Endocrine Disruptor Screening Program

................................ ................................ ............... 24 11. Preliminary Identification of Data Gaps

................................ ................................ ................ 25
11.1 Environmental Fate

................................ ................................ ................................ ..... 25
11.2 Effects

................................ ................................ ................................ ......................... 27 12. References

................................ ................................ ................................ .............................. 33 Appendix A. Screening Level Models to Evaluate Potential Importance of Drinking Water and Inhalation Exposure Pathways

................................ ................................ ........................... 35 Appendix B. Predictive Data for Parent Imazapic and its Degradates from QSAR Modeling using Ecosar v1.11

................................ ................................ ................................ .................... 37 Appendix C. Data Justification Tables for Non

- guideline Studies

................................ .......... 41Page 5 of 43



## 1. Executive S ummary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the ecological risk, environmental fate, endangered species, and drinking water

ass essments to be conducted as part of the registration review of imazapic (PC code 129041) and its ammonium salt (PC code 128943) . The problem formulation describes the methods to be used for the drinking water and ecological risk assessments in support of registration review and provides an overview of the environmental fate, ecological effects, and potential risks as sociated with the use of imazapic as well as uncertainties uniqu e to risk assessment of imazapic . This document also identifies additional st udies that would be beneficial to the conduct of an ecological risk assessment.

Data needs for ecological effects are:

 Avian Acute Oral Toxicity (850.2100)

— study conducted with a passerine species using
T GAI

 Adult Honey Bee Acute Oral Toxicity (non

- guid eline) using TGAI

 Adult Honey Bee Chronic Oral Toxicity (non

- guideline) using TGAI

 Larval Honey Bee Acute and Chronic Oral Toxicity (non

- guideline) using TGAI

 Field Testing for Pollinators (850.3040)

— may be waived pending the results of the lower tier larv al and adult honey bee acute and chronic oral toxicity studies

 Seedling Emergence and Seedling Growth (850.4100)

– Tier II study conducted with a technical end

- use product (TEP) on tomato, ryegrass and oat

 Vegetative Vigor (850.4150)

– Tier II study condu cted with a representative end

- use product on 10 plant species

The lack of ecological effects data on the toxicity of imazapic’s degradates (through aquatic photolysis) to vascular aquatic plants is considered a data gap, but no data is requested at this time. For example, if imazapic degradates approach the toxicity of parent imazapic with respect to aquatic vascular plants, than there may be implications on the risk picture for listed and non

listed species of this taxa. In the absence of any additiona l data, EFED will make conservative assumptions including using a Total Toxic Residues (TTR) approach to model exposure for vascular aquatic plants in the risk assessment and assume that all imazapic degradates have equal toxicity to vascular aquatic plant s.

Data needs for fate and exposure assessment are:

 Aerobic Soil Metabolism (835.4100)

- need three additional soils as per guidelines requirement using TGAI

 Aerobic Aquatic Metabolism (835.4300) using TGAI

 Anaerobic Soil Metabolism ( 835.42 00) using TGA I

 Soil Storage Stability Study

- to support submitted PGW stud ies (MRIDs: 47001701 and 47002001)

 Environmental Chemistry Methods and independent laboratory validations for p arent imazapic and its major d egradate s in Soil and W ater (850.6100)Page 6 of 43



## 2

. Introduct ion

Imazapic ( Figure 1 ) is an herbicide which belongs to the imidazolinone class of pesticides which also includes imazamox , imazapyr, imazethapyr, imazamethabenz, and imazaquin. All of the imidazolinone herbicides share a common mechanism of herbicidal a ction that involves the inhibition of the acetolactate synthase (ALS) enzyme (also referred to as acetohydroxyacid synthesis (AHAS) inhibitor). ALS is an enzyme found in plants and is required for the synthesis of essential branched chain amino acids ( i.e.

, valine, leucine, and isoleucine), all of which are important for plant growth (Tan et al . 2005). Animals do not synthesize these amino acids via this pathway; therefore, imidazolinone herbicides generally exhibit very little toxicity to mammals , birds, fish, or insects.

Imazapic is the common name for (±)

- 2

- [4

, 5

- D ihydro

- 4

- m ethyl

- 4

- (1

- methylethyl)

- 5

- oxo

- 1 H

imidazol

- 2

- yl]

- 5

- methyl

- 3

- pyridinecarboxylic acid and is identical to imazapyr with the addition of a methyl group on the pyridine ring:

Figure 1 : Chemical structure of imazapic (PC Code 129041)

Ammonium salt of imazapic ( Figure 2) is the common name for (±)

- 2

- [ 4,5

- Dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo

- 1 H

- imidazol

- 2

- yl]

- 5

- methyl

- 3

- pyridinecarboxylic acid monoammonium

s alt

.

Figure 2: Chemical Structure ammonium salt of imazapic (PC Code 129043)

The risk assessment will be conduc ted assuming imazapic refers to the free acid of imazapic (as drawn in Figure 1 )

. All end

- use products of imazapic contain the imazapic acid or the ammonium salt of imazapic as indicated in the use Table 1

. Fate and ecotoxicity studiesPage 7 of 43

generally did not specify whether they were conducted with the acid or ammonium salt , but t he assessment will assume that a ll fate and ecotoxicity studies w ere conducted using the free acid (TGAI) of imazapic unless other information is provided.

Imazapic was first granted a registration for peanuts in the United States in 1 99 4. Additional uses have been granted since the initial registration. The uses in th e profile to be evaluated by EFED include terrestrial non

- crop areas including rights

- of

- way, non

- residential turf, and wildlife habitat management . Details of treated crops and areas as well as application rates and methods are provided in Section 3 of th is document.

EFED evaluated the most recent ecologic al risk assessments for imazapic in association with the updated toxicity, exposure, and usage information to determine if sufficient data are available or if further updates are needed to support regis tration review. In addition, EFED considered the latest Agency science policies and risk assessment methodologies.



## 3. Use Characterization

The chemical profile produced by Biological and Economic Analysis Division (BEAD), located
in the registration r eview docket, lists the use patterns of maximum exposures for the current uses of imazapic and its ammonium salt

. BEAD’s chemical profile includes both a summary of labeled uses and application rates as well as a summary of available reported usage data. The Screening Level Usage Analysis (SLUA) and chemical profile reports conducted by BEAD showed that the main use (>98% of total pounds applied) for imazapic is on peanuts with approximately 55% of the crop treated, based on available data from 2004

— 2012 ( USEPA, 2014 a )

. This use is primarily in the states of Georgia, Alabama and Florida. Pastureland constitutes most of the remainder of imazapic use (1.4% of total pounds applied). The Bureau of Land Management (BLM) has reported increasing imazapic use from 2002 to 2011, with ~2100 pounds of active ingredient ( a.i. ) applied on ~21,200 acres in 2011 (BLM Proprietary Data, 2012). EFED will use application scenarios that result in maximum exposure scenarios for a given use for the risk assessment. Any absence of information on the labels that specifies the maximum single application rate, the application interval, the annual maximum rate allowed (expressed as pounds of acid equivalent per acre per year) (lbs a / acre/ year), or application method

, may result in ov erly conservative assumptions.

The use profile to be utilized for EFED’s risk assessment includes the terrestrial uses described
in Table 1

. The highest use rate of 0.9171 lbs a e /A (nonagricultural uncultivated areas/soils) is substantially higher than an y other use site. This application rate is associated with two labels (EPA Registration Numbers 71995

- 49 and 71995

- 51 ; both labels with imazapic ammonium salt

co

- formulated with glyphosate and diquat dibromide ) for use on small areas such as cracks and

cr evices on sidewalk s, walkways, gravel pathways, along fences and in driveways and parking

areas. This application rate is typically applied only as a spot treatment and will be modeled accordingly in the risk assessment. Information on a typical percentag e of an area that is spot treated for this use site would be useful for the risk assessment.Page 8 of 43

Table 1

. Profile of currently registered u ses of Imazapic Acid and its Ammonium Salt

Crop Max imum

Single App lication
Rate (lb ae/acre ) Annual

Max imum
N umber of App lication s or Annual Maximum Application
Rate Geographic

R estrictions Application

Method (s) End

- use

Product Labels

Agricultural Fallow/Idleland/ Conservation Reserve 0.1994 A ae 0.1994 Aerial or ground 241

- 393

241

- 409
241

- 417 71368

- 99 SD090005

Conifers 0.1859 A ae 0.1859 Aerial or ground 2935

- 557

Nonagricultural Uncultivated Areas/Soils 0.9171 B ae NS D , E Aerial D or ground 241

- 365

241

- 393
241

- 409
241

- 417
241

- 425
241

- 444 2935

- 557
7969

- 320 66222

- 141 71368

- 99 71995

- 38 71995

- 40 71995

- 47 71995

- 49 71995

- 51 71995

- 54 81927

- 19 SD090005

Pastures 0.1994 B ae 0.1994 Aerial or ground 241

- 365

241

- 417
241

- 444 66222

- 141 71368

- 99 81927

- 19 SD090005

Peanuts 0.063 8 B ae 0.063 8 ae Registered only for

u se in Alabama, Arizona, Arkansas, Florida, G eorgia, Louisiana Mississippi, Missouri, New Mexico, North Carolina, Oklahoma, Ground 241

- 364
241

- 381
241

- 444 66222

- 141Page 9 of 43

Table 1

. Profile of currently registered u ses of Imazapic Acid and its Ammonium Salt

Crop Max imum

Single App lication
Rate (lb ae/acre ) Annual

Max imum
N umber of App lication s or Annual Maximum Application
Rate Geographic

R estrictions Application

Method (s) End

- use

Product Labels

South Carolina, Tennessee, Texas, Virginia

Rangeland 0.1994 B ae 0.1994 Aerial or ground 241

- 365

241

- 417
241

- 444 66222

- 141
71368

- 99 8 1927

- 19 SD090005

Mulch 0.2 339 C ae NS Ground 241

- 425 71995

- 38 71995

- 47 71995

- 54

Ornamental 0.2339 C ae NS Ground 241

- 425 71995

- 38 71995

- 47 71995

- 54

A

- formulated as imazapic acid

B

- Both imazapic acid and imazapic ammonium salt are registered for this u se site

C

- Formulated as ammonium salt

. D

- Aerial applications on nonagricultural uncultivated areas/soils are only allowed with imazapic acid formulations and the maximum single and annual application rate for aerial applications is 0.1994 lbs ae/A

E

- NS = not specified



## 4. Conclusions from Previous Risk Assessments

The Agency has conducted previous ecological risk assessments and drinking water assessments for imazapic that serve as a basis for this problem formulation. Results of the most recent

ass essment are briefly summarized below

. Neither an endangered species assessment nor a Re

registration Eligibility Decision (RED) have been conducted by EPA for imazapic

. Several other federal agencies including the BLM and the Forest Service have previous ly conducted ecologic al risk assessments on imazapic (ENSR, 2005; SERA, 2004)



### 4.1 Ecological Risk and Drinking Water Assessments

The m ost recent EFED risk assessment for imazapic was completed in 2001 (DP Barcode:
D277341 ). EFED conducted a Drinking Water As sessment ( DWA , D267228 and D267228A ) and an Ecological Ri sk Assessment (ERA) for imazapic and its end

- product Plateau DGPage 10 of 43

herbicide for the control of weeds in pasture, rangeland, and the Conservation Reserve Program

. The acute (peak value) and chronic (yea rly average) estimated drinking water concentrations ( E DW Cs ) for the herbicide as predicted by the FIRST model were 16.8 μg ae /L and 1.46 μg

ae /L , respectively. Levels of Concern were exceeded for listed and non

- listed species of non

target terrestrial pl ants and vascular aquatic plants. The SCI

- GROW model provided estimated ground water concentrations at 13.73 μg / L

. The H ealth Effects Division’s (HED) Metabolism Assessment Review Committee (MARC) determined that the residue of concern in drinking water i s imazapic per se (USEPA

, 2001a; D275136).

A summary of c onclusions for ecological risk concerns identified in the previous ecological risk

assessment are provided in Table 2

.

Table 2 . Summary of Risk Concerns Identified for Imaza pic in Previous Assessm ents

Birds Mammals Terr.

Plants Terr. Inverts Fish BCF Aquatic

Inverts Aquatic

Plants Groundwater Contamination Persistence Degrad at es of Concern

No No Yes NA No No No Yes Potential Yes a None

Yes = at least one LOC was exceeded in previous assessments
N o = LOCs were not exceeded in previous assessments NA = RQs were not calculated previously.

a Stable to hydrolysis, soil photolysis, aerobic soil metabolism, anaerobic aquatic metabolism



### 4.1.1 Bureau of Land Management Assessment

In 2005, the Burea u of Land Management ( BLM ) completed a n ecological risk assessment for the use of imazapic and nine other herbicides to control invasive plants and weeds on approximately one million acres (ENSR, 2005). The assessment modeled both typical (0.0313 lbs a.i. /A) and maximum (0.1875 lbs a.i./A) application rates. This assessment concluded that risk to te rrestrial wildlife and fish was not predicted. Acute risk was not predicted for aquatic invertebrates, but chronic risk was predicted under a single direct sp ray scenario at the maximum application rate. Risk to terrestrial and aquatic non

- target plants was considered likely when plants or water bodies are accidentally sprayed. Risk to non

- target aquatic plants was considered likely at the maximum application rate from surface runoff in sandy soils with at least 25 inches of precipitation per year, in clay/loam watersheds with at least 50 inches of precipitation per year, and in loam watersheds with at least 100 inches of precipitation per year. For risk from spray drift, at the maximum application rate risk was predicted for listed and non

- listed terrestrial plant species for aerial applications with less than 300 feet (if conducted by forested plane) or 100 feet (for helicopters and non

- forested planes) buffe rs. Spray drift resulted in risk to aquatic plants under maximum application rates in forested areas with less than 100 foot buffers.



### 4.1.2 Forest Service Assessment

In 2004, the Forest Service completed a human health and ecological risk assessment for the use of two formulations (Pl at eau TM and Plateau DG TM , both containing the ammonium salt ofPage 11 of 43

imazapic) in its vegetation management programs (SERA, 2004) . The ecological risk assessment concluded that risk to terrestrial and aquatic animals was unlike ly. Sensitive plant species were determined to be potentially at risk by off

- site spray drift of imazapic at distances of 50 feet for ground applications or over 100 feet for aerial applications. Damage to terrestrial plants from runoff was considered po ssible in some areas but unlikely to be substantial. Vascular aquatic plants were considered to be at risk under conditions in which runoff is favored, such as in areas with clay soils and relatively high rainfall rates.



## 4.2 Clean Water Act Programs

Imaz apic is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Load (TMDL) criteria have been developed for imazapic

. Based on its chemical structure, this compou nd falls under the 50 microgram per liter New York State drinking water standard for “unspecified organic contaminants” (10 NYCRR Part 5, Public Water Systems). Aquatic benchmarks have been established for ima zapic acid and are available at http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm

. The lowest benchmark

was set at 6.1 μg/L for vascular aquatic plants and was >50,000 μg/L and 96,000 μg/L for acute

a nd chronic concerns to aquatic animals. Any data submitted or otherwise located as part of the registration review process may be used to update aquatic life benchmarks if applicable.



## 5

. Environmental Fate and Transport

Except for rapid aqueous pho tolysis, imazapic appears to be e xtremely persistent, mobile and highly soluble. Imazapic is expected to occur in an ionized form in the natural environment

. The major route of dissipation of imazapic app ears to be aqueous photolysis and transport with wat er (D256432). Therefore, contamination of ground water and surface water by imazapic ap pears possible via leaching, runoff and spray drift

. Once in ground water or s urface water where light

cannot penetrate, im azapic will be very persistent. This assessmen t is consistent with other imidazolinone herbicides.

In laboratory studies, except for rapid aqueous photolysis (t 1/2 =< 8 hou rs), imazapic is stable (≥ 94.3% parent remained after 30 days) to hydrolysis at pH 5, 7, and 9, s oil photolysis ( t 1/2 = 106 days)

, aerobic soil metabolism ( extrapolated t 1/2 = 2010 days), and anaerobic aquatic met abolism ( extrapolated t 1/2 = 2400 days). Based on batch equilibrium data conducted on six soils, imazapic appears to b e very mobile to mobile in soil (K d = 0.17

- 2.99). Th e K oc model does not appear to be valid for imaza pic as its mobility is not correlated with the organic carbon content of soil

. Volatility does not appear to be a major route of d i ssipation since very little (≤ 1%) volatile compounds were isolated in the laboratory studies and the vapor pressure of < 10

- 7 mm Hg indicates that the compound would not be volatile. Imazapic has a very low b ioconcentration factor (maximum of 0.12 in inedi ble parts) demonstrating a lack of accumulation in fish; further

, the compound was rapidly excreted within three da ys of exposure to less than the detection limits. The low K ow value of < 1 supports the concl usion of low bioaccumulation of imazapic.

In th e field

, imazapic proved to be mobile and persistent

. Imazapic terrestrial field dissi pation half

- lives ranged from 31 to 223 days in six sites of AR, FL, GA (2 sites), NC, and TX , with thePage 12 of 43

average of 122 days, and median 102 days, for the currently regist ered liquid formulations. Imazapic photo degradates were not monitored in the field studies

. In a prospective gr ound water study conducted in NC

, after application of Plateau® ( an aqueous solution formulation; 22.2%

a.e. ) residues of imazapic were detected at levels ≤ 0.08 ppb in 3 (shallow) of the 9 wells. Imazapic degradate CL 354825 was not detected in shallow or deep wells. In another study conducted in GA after application of Cadre® DG ( a dispersible granule formulation; 70% a.i. ) residues of imazapic w ere not detected above the LOD in any shallow or deep monitoring wells. This GA site , however, did not represent conditions that maximize imazapic persistence and mobility as determined during a review of the study protocol ( USEPA 1999, D25695 7 )

.

Registra nt

- submitted data characterizing the physical, chemical, fate and transport characteristics associated with imazapic are summarized below in Table 3

.

Table 3 : Physioc hemical Properties and Environmental Fate Characteristics of Imazapic Acid

Parameter Va lue 1 Description Source (MRID)

Selected Physical/Chemical Parameters

CAS No.: 104098

- 48

- 8

IUPAC name 2

- [(RS)

- 4

- isopropyl

- 4

- methyl

- 5

- oxo

- 2

- imidazolin

- 2

- yl]

- 5

- methylnicotinic acid

CAS name 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo

- 1H

- imidazol

- 2

- yl ]

- 5

- methyl

- 3

- pyridinecarboxylic acid

Smiles O=C(O)c1c(ncc(c1)C)/C2=N/C(C(=O)N2)(C(C)C)C

Molecular Mass of Imazapic (Molecular Formula)

a nd its ammonium salt 275.3 g/mol (C 14 H 17 N 3 O 3 ) 292.3 g/mol Imazapic acid

Ammonium Salt IUPAC Site

Vapor pressure (25°C) <1.0 x 10

- 7 mm Hg Non

- volatile under normal field conditions 4271 140 3

Aqueous solubility (25  C) ppm 2,150; 36,000; 479,000; and
518 ,00 0 In d e

- ionized water, pH5,

pH7, and pH9 , respectively 427114 03

Apparent ( the sum of the ionized and non

- ionized forms ) Log octanol

- to

- water partition coefficient (K OW ) pH 4: 0.462 pH 5: 0.158 pH 6: 0.0318 pH 7: 0.0101 pH 8: 0.0053 pH 9: 0.0024 Not likely to bio

accumulate 427114 03

Persistence

Hydrolysis: Half

- life (25±1  C) pH 5: Stable pH 7: Stable pH 9: Stabl e Not a major degradation pathway 4271 1444

Aqueous Photolysis: Half

- life (25±1  C) pH 5: 7.2 hrs. pH 7: 6.0 hrs. pH 9: 6.2 hrs. M ost rapid degradation

process 43320311Page 13 of 43

Table 3 : Physioc hemical Properties and Environmental Fate Characteristics of Imazapic Acid

Parameter Va lue 1 Description Source (MRID)
Soil Photolysis: Half life (25±1  C ; pH: 5.4 ) 106 d (Sassafras sandy loam ) Not a major degradation pathway 4332031 2

Aerobic Soil Metabolism: Extrapolated Half

- life (25±1°C) 2010 d Sassafras sandy loam soil pH of 5.2 and 1.3% OM 42711445

Anaerobic Aquatic Metabolism: Extrapolated Half

- life (25±1°C) 2400 d

-- 4332031 3

Mobility

Soil

- wate r partition coefficients (K d

- ads )

Orga nic carbon

- normalized partition coefficients (K OC ) 0.19, 058, 0.82, 2.8, and 4.1 l/kg

7 to 267 Very m obile to mobile 42711446

Field Dissipation

Terrestrial Field Dissipation : Half

life and DT 75 Leaching depth 31 d (0

- 6 in. depth);
DT 75 : 90 d Leached to 6 in. depth 1 Near Jamesville , NC Sandy l oam soil 43320314

2 23 d (0

- 6 in. depth);
DT 75 : >120 d Leached to 6 in. depth Shoffner , A R
L oam soil 43320314

184 d (0

- 6 in. depth);
DT 75 : >120 d Leaching to 6 in. depth 1 Pinehurst, GA Sandy loam soil 43320314

9 3 d (0

- 18 in. depth);
DT 75 : 240 d Leached to 18 in. depth Snook, TX S ilt y loam soil 43320314

104 d (0

- 18 in. depth);
DT 75 : 299 d Leached to 18 in. depth Montezuma, GA
L oam y sand soil 43320314

99 d (0

- 18 in. depth);
DT 75 : 450 d Leached to 18 in. depth Malone, FL Loamy sand soil 43320314

Small

- Scale Prospective Ground

Water Monitoring Study Parent detected in 3 of 9 wells , CL 354825 was not detected in any wells.

Neither parent nor CL 354825 were detected ab ove LOD in any wells. Lucy loamy sand

, Richmond County, NC ( Plateau® ; an aqueous solution formulation)

Eustis sandy loam

, Dooly County, GA ( Cadre® DG

, dispersible granule formulation ) 47001701

47002001

Fish BioconcentrationPage 14 of 43

Table 3 : Physioc hemical Properties and Environmental Fate Characteristics of Imazapic Acid

Parameter Va lue 1 Description Source (MRID)

Fish Bioaccumulation Facto rs ( 28 d BCFs for bluegill sunfish ) Edible: < LOQ Inedible: 0.12X Whole Body: 0.10X Depura tion: 50% and > 99% by day 3 and 14

. Does not bioaccumulate in fish 43320315

Abbreviations:  C

- degrees Celsius; d = day; DT

- disappearance time; hrs. = hours; in. = inch; l = liters; kg = kilograms; LOQ = level of quantitation; < = less than;
Notes:

1 Except for one replicate that showed the parent leached below 6in. depth.

The l abor atory data indicate the only iden tifiabl e degradation process of imazapic that i s rapid enough to yield detectable degradates i s photolysis. In t he aqueous photolysi s study, s i x degradates , includi ng CO 2 , were i dentified at concentrations >l0 % of the applied ( Table 4 )

. I n the soil photolysis study , o ne major product was formed which a ccounte d for greater than 10% of the applied dose (11%) . This product was identi fied as the diacid, AC 312,622, and it is a common degradate for imazamox, another imidazolinone pesticide

, and imazapic. In addition,

t here were three unidentified radiolabele d components, each of which represented between 3 to 8% of the applied dose.

In an anaerobic aquatic metabolism study, there were no metabolites detected w hich accounted for greater than 10% of the a pplied dose, or were present at leve ls greater than 0.0 1 ppm. There were no metabolites detected in the aerobic soil metabolism study, and imazapic d egradates were not monitored in the field dissipation studies. The transformation product CL 354825 was analyzed for in a small

- scale PGW s tudy in North Carolina on sand y soil and it leached into all soil depths. It was not detected , however, above the LOQ in soil pore

- water samples with the exception of three samples, concentrations of 0.06 ppb

, and was not detected in shallow or deep wells

. Below T able 3 presents identified major degradates and their maximum percent of applied radioactivity.

Table 4 . Degradates identified and maximum percent of applied radioactivity in the

aqueous and soil photolysis stud ies

.

Degradates Structure Study Type (Reference) Per cent of

applied radioactivity (%) at

pH5 pH7 pH9 Carbon dioxide (C02) 45.5 21.0 10.3Page 15 of 43

5

- methyl

- 3

- pyridinecarboxylic acid CAS: 3222

- 49

- 9 5

- Methylnicotinic acid Smiles String: C1=C(C=NC=C1C(O)=O)C

MF: C 7 H 7 NO 2 MW : 137.14 CL 263,407 Aqueous Photolysis MRID 4332031 1 29.9 17.2 15.7

2

- [(1

- carbamoyl

- 1,2

- demethypropyl) carbamoyl]

- 5

- methyl

- nicotinic acid Smiles String: C1=C(C=NC(=C1C(O)=O)C(=O)NC(C( C)C)(C(=O)N)C)C

MF: C 14 H 19 N 3 O 4 CL 290,610 Aqueous Photolysis MRID 4332031 1 30.8 29.0 41.3

5

- methyl

- 2

- 3

- pyridine dicarboxylic acid Smiles String: C1=C(C=NC(=C1C(O)=O)C(=O)O)C

MF: C 8 H 7 NO 4 CL 2 90,811 Aqueous Photolysis MRID 4332031 1 13.0 10.3 5.3

2

- carbamoyl

- 5

- methyl

- nicotinic acid Smi les String: C1=C(C=NC(=C1C(O)=O)C(=O)N)C

MF: C 8 H 7 NO 3 Aqueous Photolysis MRID 4332031 1 10.5 12.9 9.7Page 16 of 43

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid

Smiles String (2

- ring structure) : C1=C(C=NC2=C1C(=O)OC2O)C

Smiles String (1

- ring stru cture): C1=C(C=NC(=C1C(=O)O)C=O)C Aqueous Photolysis MRID 4332031 1 18.4 43.3 44.3

Name: 3,5

- Pyridinedicarboxylic acid, 2

- (4

- isopropyl

- 4

- ethyl

- 5

- oxo

- 2

- imidazolin

- 2

- yl)

-

Smiles String: C1=C(C=NC(=C1C(O)=O)C2=N C(C(N 2)=O)(C(C)C)C)C(O)=O

MF : C 14 H 15 N 3 O 5 MW: 305.29
CL 312.622 Soil Photolysis
MRID 43320312 11 (30 d)

Abbreviations: MF

- Molecular Formula ; MW

- Molecular Waight; d

– days.



## 6

. Receptors

Tables 5 and 6 provide a summary of the taxonomic groups tested to characterize the potential acute and chronic ecological effects of imazapic

. In addition, the table s provide a preliminary overview of the potential acute toxicity of imaz apic by providing the a cute toxicity classifications. No t oxicity data f or any imazapic degradate s is available

. It was unclear from some of the submitted toxicological studies whether they were conducted with imazapic acid or imazapic ammonium salt, however for the risk assessment , EFED will assume t hat all studies

were conducted with the acid, unless information is provided to contradict this assumption. Although this is an uncertainty, if any ecotoxicological studies were conducted with the ammonium salt instead of the acid, than by using the acid equivalency EFED would only be underestimating actual toxicity by approximately 6%

.Page 17 of 43

Technical grade imaza pic is classified as practically non

- toxic to freshwater and saltwater fish and aquatic invertebrates on an acute exposure basis ( T able 5 )

. No effects were seen in chronic aquatic studies conducted with freshwater fish and invertebrates. Chronic exposure effect data for saltwater fish and invertebrates have not been submitted to the Agency. Duckweed ( Lemna gibba ) was the most sensit ive aquatic plant species to imaza pic with an IC 50 of 6.22 ppb ae /L and a NOAEC of 2.58 ppb ae/L ; h owever, growth inhibition was generally not observed in freshwater or estuarine/marine non

- vascular aquatic plants based on toxicity test ing with maximum con centrations of 44.1

— 67.4 ppb ae /L. However, in a limit test with freshwater diatoms ( Navicula pelliculosa ), inhibition was 11% at the limit dose of 46.4 ppb, which did not include one presumed outlier that would have resulted in inhibition of 32.9% at the limit dose.
EPA does not currently classify toxicity to aquatic plants.

Previous assessments (USEPA, 2001) indicated potential for risk to listed and non

- listed species of aquatic vascular plants. No data is available for the toxicity of imazapic degrada tes to aquatic plants or other aquatic taxa . Other chemicals in the imidazolinone class ( i.e. imazapethyr) have some degradates that are analogous to imazapic’s degradates and for which empirical data is available. For example, two degradates of imazapet hyr (CL 290084 and CL 271197) are analogous to imazapic’s degradates, CL 263,407 and CL 290,811, respectively , except that imazapethyr’s degradates have attached ethyl groups while imazapic’s degradates only contain attached methyl groups. Those imazapeth yr degradates were more toxic to several aquatic taxa including daphnids and green algae and although less toxic than parent imazapethyr to duckweed were still reasonably sensitive (NOECs ranged from 23.54 μg a.i./L to 49.8 μg a.i./L).

A quatic invertebr ates and nonvascular plants would likely have to be > 5 orders of magnitude more sensitive to imazapic degradates than parent imazapic in order to approach levels of concern. However, for aquatic vascular plants, if imazapic degradates approach the toxici ty of parent imazapic than there may be implications on the risk picture for listed and non

- listed species of aquatic vascular plants. The lack of data on imazapic degradates’ toxicity to aquatic vascular plants is considered a data gap, but no additional data is requested at this time. EFED attempted to see if quantitative structural activity relationships (QSAR) could be used to estimate the toxicity of imazapic degradates (Appendix B )

. However, this analysis (conducted using ECOSAR v1.11) found that QS AR relationships poorly predicted the actual toxicity of parent imazapic to green algae (though had better predictive capacity for aquatic invertebrates and fish) and lacked predictive capability for toxicity to duckweed and would therefore be inappropriat e to use to characterize the toxicity of the degradates to aquatic vascular plants

. For the risk assessment, in the absence of any additional aquatic vascular plant toxicity data on the degradates, EFED will conservatively characterize this risk by utiliz ing a TTR approach . In this approach, a single exposure concentration is estimated for total residues ( i.e. parent imazapic + the five degradates identified in the aqueous photolysis study) and compared to a representative toxicity endpoint for the parent ( i.e. assumes equal toxicity of each degradate to parent imazapic). This approach may not be sufficiently conservative if degradates are actually more toxic than parent imazapic, however available data for other chemicals in the imidazolinone class ( i.e. imazapethyr) indicate that for the aquatic taxa most likely to be at risk (aquatic vascular plants), the degradates are not as toxic as the parent compound (USEPA, 2014b)

.Page 18 of 43

Table 5 . Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studie s for Imazapic Acid

Taxonomic Group Study

Type Tested Species Toxicity Value Acute Toxicity Classification Source

(Study Classification) Comments

Freshwater fish 1 Acute Bluegill sunfish ( Lepomis macrochirus ) Rainbow trout ( Oncorhynchus mykiss ) 96

- Hr LC 50 >

100 ppm ae Practically

non

- toxic 42711434 & 42711435

( A cceptable) Max mortality was 10% at the limit concentration

Chronic Fathead minnow

Pimephales promelas 28

- D NOAEC

= 96 ppm ae LOAEC > 96

ppm ae N/A 44728202 (Acceptable) No mortality or sublethal effects

Freshwater invertebrates Acute Water Flea ( Daphnia magna ) 48

- Hr E C 50 >

100 ppm ae Practically

non

- toxic 42711437 (Acceptable

No mortality or sublethal effects

Chronic Water Flea

( Daphnia magna ) 21

- D NOAEC

= 96 ppm ae LOAEC > 96

ppm ae N/A 447 28201 (Acceptable) No mortality or sublethal effects

Estuarine/ marine fish Acute Sheepshead Minnow ( Cyprinodon variegatus ) 96

- Hr LC 50 >

98.7 ppm ae Practically

non

- toxic 44817702 (Supplemental)

Chronic No data

Estuarine/ marine invertebrates Acute My sid shrimp (Americamysis bahia) 96

- Hr LC 50 >

97.7 ppm ae Practically

non

- toxic 44817704 (Acceptable)

No mortality of sublethal effects
Chronic No data

Aquatic plants and algae Vascular Duckweed ( Lemna gibba ) 14

- D IC 50 =

6.22 ppb ae (95% CI: 5.75

— 6.75 ) NOAEC = 2.58 ppb ae N/A 43320310 ( A cceptable) Tier II study with technical grade material

, number of fronds at 14 days was most sensitive.

Non

vascular Marine Diatom

Skeletonema

costatum 120

- Hr IC 50 >

44.1 ppb ae
NOAEC = 44.1 ppb ae N/A 43320310 ( A cceptable) Tier 1 study with technical grade material

, Day 0 Concentrations (Day 5 concentrations had decreased by over 40%)

1 Freshwater fish may be surrogates for aquatic

- phase amphibians.

Imazapic is practically non

- toxic to birds on an acute oral ba sis and a dietary basis, and it is practically non

- toxic to mammals on an acute oral exposure basis ( Table 6 ). No acute passerine bird toxicological data is available. No mammalian inhalation toxicity data is available for thisPage 19 of 43

chemical , however due to i ts low vapor pressure, inhalation exposure is not expected. Hatchling body weight was reduced in the mallard reproduction study at 994 mg a.e./kg

- diet while in the bobwhite reproduction study, effects were seen on hatchling body weight, number of live embr yos/number of viable embryos and number of hatchlings/number of live embryos at 1907 mg a.e./kg

- diet. No reproductive effects were observed in the chronic mammal study at concentrations up to 20,000 ppm

.

Although no mortality was observed in the acute o ral and dietary studies with bobwhite and mallard, sublethal effects of reduced food consumption were observed in the mallard acute oral study and both the mallard and bobwhite subacute dietary studies. Chronic effects were also seen on hatchling body wei ght for both mallards and bobwhite quail and additional reproductive effects (reduced survival of live embryos and hatchlings) were seen in the bobwhite quail reproduction study. Additionally the maximum application rate of 0.9171 lbs ae/A (for the spot t reatment on nonagricultural uncultivated areas/soils use site) results in upper bound Kenaga residue estimates on short grass that are greater than 1 / 10 the highest dose tested in the acute oral studies. In the absence of additional data, risk to listed a vian species may be uncertain. Therefore, a new avian acute oral study using a passerine species is needed for the risk assessment to evaluate acute risk to listed avian species. Maximum use rates for all other imazapic use sites are significantly lower and would not result in the need for a passerine study to reduce potential uncertainties regarding acute oral

- based exposure for listed avian species. If the maximum application r ate from the spot treatment was reduced by approximately 45% to 0.50 lbs ae/ A, than the upper bound residue estimates would be sufficiently low on all dietary items such that additional avian data would not be needed.

Acute contact toxicity to bees was low, with observed mortality being 25% at the highest treatment level of 100 μg ae/

bee

. Acute oral toxicity data is not available for adult bees nor is chronic toxicity data available for adult bees or acute or chronic data available for larval bees

. Data on pollinator toxicity is required to sufficiently evaluate risk to pollina tors.

Terrestrial p lant seedling emergence and vegetative vigor data was original ly considered acceptable, but are now being downgraded to supplemental as they were conducted with TGAI and not an end

- use product

. Additionally, in the available Tier 2 te rrestrial plant studies

, continuation tests were performed as a result of the fact that the initial tests did not include low enough concentrations to allow determination of the NOAEC and/or IC 25 . EFED does not support combining the results of multiple t ests for statistical analysis of assessment endpoints. Therefore, for those species/tests where the NOAEC/IC 05 and the IC 25 both cannot be determined from only the base test or the continuation test alone, the study has been further downgraded to invalid for the vegetative vigor test (supplemental

— qualitative for the seedling emergence test) . Due to these factors a new vegetative vigor study is requested on the full standard suite of species using a typical end

- use product (TEP). Additionally, new seedli ng emergence data is requested for tomato, oat, and ryegrass using a TEP.

In the case of the seedling emergence test with ryegrass, EFED believes that a NOAEC and IC 25 can be determined from the continuation test data alone. However, raw test data (other than phytotoxicity data) for ryegrass were not included in the test report (MRID 43320308). ThereforePage 20 of 43

if raw test data for ryegrass dry weight and plant height are provided for the continuation test , new seedling emergence test data for ryegrass would no t be needed.

No toxicity data is available for imazapic’s degradates.

Table 6 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Imazapic
Taxonomic Group Study

Type Tested Species Toxicity
Value Acute Toxicity

Classif ication Source

(Study Classification) Comments

Birds 1 Acute Bobwhite quail ( Colinus virginianus ) & Mallard Duck ( Anas platyrhynchos ) 21

- D

LD50 > 2150 mg

ae /kg

- bw Practically non

toxic 42711430 &

42711431 ( Acceptable ) No mortality or sublethal effects in t he bobwhite study. Food consumption was reduced 25% in the 2150 mg/kg test group in the mallard study for days 1

- 3.

Sub

- acute dietary Bobwhite quail

( C. virginianus) & Mallard duck (

A. platyrhynchos) 8

- D LC50

> 4685 mg ae/kg

- diet Practically non

toxi c 42711432 & 42711433

(Supplemental)
No treatment

- related mortality. Food consumption was reduced in both the mallard and bobwhite studies.

Chronic Bobwhite quail

( C. virginianus ) NOAEC =

1187 mg

ae /kg

- diet LOAEC = 1907 mg

a.e ./kg

- diet N/A 44638102 ( Acceptable ) Endpoints affected : 14

- d hatchling weight, live embryos/viable embryos, hatchlings/live embryos

Mallard duck (

A. platyrhynchos ) NOAEC =

538 mg

ae /kg

- diet
LOAEC = 994 a.e./kg

- diet N/A 44638101 ( A cceptable) Endpoints affected: 14

- D hatchling weight

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) LD 50

>5000 mg

ae /kg

- bw Practically non

toxic 42711407 ( A cceptable)

No mortality

.

Acute Inhalation No Data

-- N/A N/APage 21 of 43

Table 6 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Imazapic
Taxonomic Group Study

Type Tested Species Toxicity
Value Acute Toxicity

Classif ication Source

(Study Classification) Comments

Chronic Laboratory rat 14

- Week
NOAEC > 20,000 mg

ae /kg

- diet
LOAEC = 20,000 mg ae/kg

- diet N/A 43320305 ( A cceptable) (1205 mg ae /kg

bw /day M ; 1484 mg

ae /kg

- bw /day F)

. No effects observed.

Insects Acute

contact Honey bee

( Apis mellifera L. ) 48

- Hr

LD 50 > 100

μg a.e. /bee NOEC = 36 μg

a.e. /bee Practically non

toxic 427114 38 (Acceptable)

Study mortality = 25% at limit dose.

Acute Oral Honey bee

( Apis mellifera L. ) No Data N/A N/A

Chronic
10

- Day Honey bee

( Apis mellifera L. ) No Data N/A N/A

Larval Emergence Honey bee

( Apis mellifera L. ) No Data N/A N/A

Terrestria l plants Seedling

Emergence Dicot

– cabbage

Brassica oleracea IC 25 =

0.00 042 lbs ae/acre
IC 05 = 0.000 14 lbs ae/acre N/A 43320308 ( Supplemental

— Quantitative for 5 species, Qualitative for tomato) T GAI was tested. Dry weight most sensitive parameter. For

c abbage, IC 25 and IC 05

were based on continuation data only.

Monocot

– onion ( Allium cepa ) 21

- D IC 25

= 0.0018 lbs ae/acre NOAEC = 0.0010 lbs ae/acre N/A 43320308 ( Supplemental

— Quantitative for 2 species, Qualitative for oat and ryegrass ). Technical was tested. Dry weight most sensitive parameter. For onion, NOAEC and IC 25

were based on continuation data only.

Vegetative vigor Dicot

— No Data N/A

-- 43320309 (Supplemental

— Qualitative for 5 species, invalid for tomato ) . Test material was TGAI.Page 22 of 43

Table 6 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Imazapic
Taxonomic Group Study

Type Tested Species Toxicity
Value Acute Toxicity

Classif ication Source

(Study Classification) Comments

Monoco t

-- No
Data N/A

-- 43320309 (Supplemental

— Qualitative for ryegrass, invalid for corn, onion and oat). Test material was TGAI

1 Birds represent surrogates for terrestrial

- phase amphibians and reptiles.

A review of the Ecological Incident Information Sys tem (EIIS, version 2.1) and the Avian Monitoring Information System (AIMS) was completed on July 2, 2014. There is only one reported incident in EIIS for imazapic acid (described below) and no reported incidents for imazapic’s ammonium salt. The single r ep orted incident in EIIS indicated effects on non

- target terrestrial plants (crop damage) and the likelihood of the effects being caused by imazapic was considered possible

. No ecological incidents involving imazapic were identified in AIMS

. In addition to the incident recorded in EIIS , additional incidents have been reported to the Agency in aggregated incident reports. Pesticide registrants report certain types of incidents to the Agency as aggregate counts of incidents occurring per product per quarter. 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 oth er terrestrial invertebrates. For imazapic acid

, registrants have reported 0 minor fish and wildlife, 1 minor plant, and 0 other non

- target incidents. For imazapic’s ammonium salt, registrants have reported 1 minor fish and wildlife , 11 minor plant and 0 other non

- target incidents

. Incident databases will be reviewed again at the time of the risk assessment.

Incident I011838

- 012 in June, 2001 in Mitchell County, GA found 70 acres of peanuts had phytotoxic symptoms and stand reduction after application with imazapic. Glyphosate, bentazon, fluazifop

- butyl, and flumioxazin were also applied, but application rates were not provided in the report for any of the herbicides except for flumioxazin which was applied at 3 oz/Acre. The certainty of injury being attributed to the non

- target plants was categorized as probable for flumioxazin and possible for imazapic and the other herbicides . It was undetermined whether this use was in accordance with the registered use for imazapic and the other herbicides, excep t for flumioxazin for which it was considered a registered use.



## 7

. Exposure Pathways of Concern

The environmental fate properties and use patterns of imazapic indicate runoff

, drift , and leaching from imazapic applications represent potential transport mechanisms of imazapic to aquatic and terrestrial organisms.

The d rinking water exposure pathway for birds and mammals w as screened using the SIP (Screening Imbibition Program) screening method

. The inhalation exposure pathway is typicallyPage 23 of 43

evaluated us ing the STIR (Screening Tool for Inhalation Risk) screening method. SIP and STIR are described in detail at: http://www.epa.gov/oppefed1/models/terrestrial/index.htm . Because of the high water solubility of imazapic under certain conditions ( e.g. neutral to basic conditions)

, the drinking water pathway was found to be an exposure pathway of potential concern. SIP results are presented in Appendix A

. The inhalation exposure pathway could not be evaluated using STIR as a result of the lack of mammalian inhalation data. However, due to the low vapor pressure (< 1 x 10

- 7 mmHg), the inhalation exposure pathway is not considered likely to be an

exposure pathway of potential concern.



## 8. Analysis Plan

8.1 Stressors of Concern

8.1.1 Ecological Risk

The stressor of ecological concern for terrestrial and aquatic organisms is the parent compound, imazapic

.

8.1.2 Drinking Water

HED MARC determined that the residue of concern in drinking water is imazapic per se (Memo,
06/07/2001 , W. Donovan, et al., D275136). The refore, the chemical that will be assessed in drinking water from surface and ground water is the parent compound only

.



### 8.2 Measures of Expo sure

8.2.1 Modeling of Ecological Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.go v/pesticides/science/models_db.htm

.

Screening level calculations suggested that drinking water pathway may be significant for terrestrial organisms. This exposure pathway may be further considered at the time of the risk

assessment ( Appendix A ).

8. 2.2 Modeling of Drinking Water in Human Dietary Risk Assessment

The drinking water assessments conducted to support future human health risk assessments of imazapic will incorporate modeling of imazapic in surface and ground water. Since the last drinking water assessment was conducted, EFED has updated its surface and ground water models, the drinking water modeling input parameters, and the percent crop ped area (PCA) guidelines. Through the course of the imazapic registration review, the Agency will det ermine whether a revised drinking water assessment will need to be conducted. For all modeling, input parameters are selected according to the current input guidelines, and where in question aPage 24 of 4 3

conservative approach is taken in the selection of half

- lives. Descriptions of all executable versions of current models for drinking water exposure can be obtained from the following URL link: http://www.epa.gov/oppefed1/models/water/

8.2.3 Available Water Q uality Monitoring Data

EFED will consider all ground and surface water monitoring data available to us, and will conduct a comprehensive evaluation of the data for the risk assessment. The data that may be considered include the United States Geological Survey (USGS) National Water

- Quality Assessment (NAWQA) Program monitoring data , and any State data available at the time of risk

assessment

.



### 8.3 Measures of Effect

Toxicity data presented in Section 6 of this prob lem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) (USEPA, 2007 c ), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communities.



## 9. Endangered Species Assessment

Consisten t with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally threatened and/or endangered (listed) species from registered uses of pesticides in registration review . The process for evaluating poten tial risks to listed species is further described at http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm

. Other agencies (USDA, Forest Service) may have previously cond ucted endangered species risk assessments for various use sites ( e.g. rangeland, conservation reserve program land) , which will be examined at the time of risk assessment.



## 10. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA rev iews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and ge neral or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reprodu ctive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests andPage 25 of 43

chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the Problem Formulation for Reg istration Review for imazapic, 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), imazapic is subject to the endocrine s creening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produce d by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to ide ntify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening 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 designed to identify any adverse endocrine

- related effects caused by the substance, and establis h a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tie r 1 screening battery, please visit our website. 2



## 11

. Preliminary Identification of Data Gaps

11.1 Environmental Fate

Table 7 identifies envi ronmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data for imazapic acid are needed to support the risk assessment

. A guideline

- compliant aerobic soil metabolism study (835.4100) containing at least three different soil types is required to better characterize rates of transfo rmation of imazapic , and a guideline aerobic aquatic metabolism study (835.4300) and anaerobic soil metabolism are requested

. In addition, s oil st orage stability data are requested and

t he analytical method validation report needs to be provided to support the PGW studies ( MRIDs: 47001701 and 47002001 )

.

1 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

2 http://www.epa.gov/endo/Page 26 of 43

All studies should be conducted on imazapic acid, its end use product or its TGAI, and its degr adate where appropriate ( e.g

. ECMs and storage stability).

Table 7 . Available envi ronmental fate data for imazapic and remaining data gaps.

158 Guideline (OPPTS) Description MRID Classification Data Gap? Comments

835.1240 (163

- 1) Adsorption/

Desorp tion 42711446 Acceptable No

--

835.2120 (161

- 1) Hydrolysis 42711444 Acceptable No

--

835.2240 (161

- 2) Photodegradation

in Water 4332031 1 Acceptable No

--

835.2410 (161

- 3) Photodegradation

on Soil 4332031 2 Supplemental No

--

835.4100 (162

- 1) Aero bic Soil

Metabolism 42711445 Acceptable Yes Need three additional
soils using TGAI

.

835.4200 (162

- 2) Anaerobic Soil

Metabolism None Yes Need guideline study for TGAI.

835.4300 (162

- 4) Aerobic A quatic

metabolism None Yes Need guideline study for TGAI.

835.4400 (162

- 3) Anaerobic

Aquatic Metabolism 43320313 Acceptable No

--

835.6100 (164

- 1) Terrestrial Field

Dissipation 43320314 Supplemental No

--

850.6100

Environmental

Chemistry Method: Soil 4332031 4 Acceptable Yes The available method supports terre strial field dissipation study

. However, any update s to the an alytical methods

are requested to be submitted.Page 27 of 43

Table 7 . Available envi ronmental fate data for imazapic and remaining data gaps.

158 Guideline (OPPTS) Description MRID Classification Data Gap? Comments

Freezer Storage Stability: (in soil) 4332031 4

47001701 47002001 Yes In NC PGW study s oil samples were stored for a maximum of 32 months

. Availa ble storage stability data indicate that residues of imazapic are stable in frozen soil for at least 24 months and residues of CL 354

, 825

are stable in frozen soil matrices for at least 24 months

. Adequate storage data are req uired to support the PGW study

. 835.7100 ( 166

- 1 )

Prospective

Ground

- Water Monitoring Study 47001701

47002001 Supplemental No 1 The independent laboratory validation (ILV) of analytical methods (soil and water) were conducted but data were not provided in the study report. The ILV of EC Ms are required to be submitted. Clarifications on length of sample storage (GA) and s torage length for field water spikes (NC) are req uired

. 850.1730 (165

- 4) Fish

Bioconcentration
Factor 43320315 Acceptable No

--

1

- Additional information is requ ested

.



### 11. 2 Effects

Tables 8 and 9 identify ecological effects 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.Page 28 of 43 Table 8 . Avail able ecological effects data for aquatic organisms exposed to imazapic and remaining data gaps.

OCSPP Guideline Data

Requirement Submitted

Studies (MRID) Study

Classification Are data

needed to conduct risk assessment? Justification and Assumptions

EPA will Make in Absence of Data

850.1010 Freshwater

invertebrate acute toxicity 42711437 Acceptable No

850.1025 850.1035 850.1045 850.1055 Saltwater

invertebrate acute toxicity 44817704

44817703 Supplemental

Supplemental No

850.1075 Freshwater

f ish acute toxicity 42711434 Acceptable No

42711435 Acceptable

850.1075 Saltwater fish

acute toxicity 44817702 Supplemental No

850.1300 Freshwater

invertebrate life cycle 44728201 Acceptable No

850.1350 Saltwater

invertebrates life cycl e No data N/A No No studies have been submitted. Exposure is estimated to be low, no acute toxicity was observed in the acute saltwater invertebrate studies and no chronic toxicity was observed in the chronic freshwater invertebrate study. Therefore,
EF ED will use the NOAEC from the freshwater invertebrate life cycle study (96 ppm) as the chronic saltwater invertebrate endpoint unless additional data is available.

850.1400 Freshwater

fish early

- life stage 44728202 Acceptable No

850.1400 Saltwater fish

early

- life stage No data No No studies have been submitted. Exposure is estimated to be low, no acute toxicity was observed in the acute saltwater fish study and no chronic toxicity was observed in thePage 29 of 43 Table 8 . Avail able ecological effects data for aquatic organisms exposed to imazapic and remaining data gaps.

OCSPP Guideline Data

Requirement Submitted

Studies (MRID) Study

Classification Are data

needed to conduct risk assessment? Justification and Assumptions

EPA will Make in Absence of Data

chronic freshwater fish study. Therefore, EFED will use the NOAEC from the freshwater fish early life stage study (96 ppm) as the chronic saltwater fish endpoint unless additional data is available.

850.1500 Fish life cycle No data No Data have not been submitted to fulfill this guideline. A data gap was not identified as these data are not necessary for risk assessment at this time.

850.4400 Aquatic plant

Toxicity Test using Lemna

spp. 43320310 Acceptable No

850.4500 Algal toxicity 43320310 Acceptable No

850.4550 Cyanobacteria 43320310 Acceptable NoPage 30 of 43 Table 9 . Available ecological effects data for terrestrial organisms exposed to imazapic and remaining data

gaps.

OCSPP Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed for risk assessment? Justification and Assumptions EPA

will Make in Absence of Data

850.2100 Avian oral

toxicity 42711431 Acceptable Yes An acute oral study with a passerine species has not been submitted to the agency. A data gap is identified at this time due to sublethal effects in the avian acute oral and dietary studies, chronic effects in the avian reproduction studies and the maximum application rate of 0.9171 lbs ae/A (nonagricultural uncultivated areas/soils) which results in expected maximum EECs that are greater t han 1/10 the highest application rate tested in the avian acute oral studies where sublethal effects were observed. Risk to listed avian species from the maximum application rate would not be able to be precluded without this data. Other use patterns for imazapic have greatly reduced application rates that would not trigger this data gap. Study should be conducted on imazapic acid. 42711430 Acceptable

850.2200 Avian dietary

toxicity 42711433 Acceptable No

42711432 Acceptable

850.2300 Avi an

reproduction 44638101 Acceptable No

44638102 Acceptable

Non

guideline Avian

inhalation No Data N/A No Data have not been submitted to fulfill this guideline. A data gap was not identified as these data are not necessary for risk assessment at thi s time.

850.3020 Honey bee

acute contact toxicity 42711438 Acceptable NoPage 31 of 43 Table 9 . Available ecological effects data for terrestrial organisms exposed to imazapic and remaining data

gaps.

OCSPP Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed for risk assessment? Justification and Assumptions EPA

will Make in Absence of Data

850.3030 Honey bee

residue on foliage No Data N/A No Data have not been submitted to fulfill this guideline. A data gap was not identified as these data are not necessary for ris k assessment at this time.

Non

guideline Honey bee

acute oral toxicity No Data N/A Yes Although acute contact data are available for honey bees, a study is needed to evaluate the ingestion route of exposure to complete the risk assessment for pollinators. Although EPA has not developed a guideline for this study, OECD TG213 may be used to assess the acute oral exposure pathway for adult bees. Study should be conducted with imazapic acid.

Non

guideline Honey bee

chronic oral toxicity No Data N/A Yes Chron ic (repeated dose) data is needed on adult honey bees to evaluate chronic risk to pollinators for the risk assessment. Although EPA has not developed a guideline for this study, guidance for a 10

- day oral toxicity study is currently in development by
OECD

. A protocol should be submitted prior to study initiation. Study should be conducted with imazapic acid.Page 32 of 43 Table 9 . Available ecological effects data for terrestrial organisms exposed to imazapic and remaining data

gaps.

OCSPP Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed for risk assessment? Justification and Assumptions EPA

will Make in Absence of Data

Non

guideline Honey bee

larval acute and chronic oral toxicity No Data N/A Yes In addition to the adult honey bee data gaps identified above, data is needed for the additional honey bee life stage of larvae to complete the risk assessment for pollinators. Although EPA has not developed a guideline for these studies, OECD TG237 may be used to assess acute oral effects on larvae. Chronic (repeat dose ) study guidance for assessing chronic oral toxicity to honey bee larvae is currently in development by OECD. A protocol should be submitted prior to study initiation. Study should be conducted using imazapic acid.

850.3040 Field testing

for pollinat ors No Data N/A Yes Data have not been submitted to fulfill this guideline. Results from lower tier studies should inform the conduct of the field test to address remaining uncertainties. Pending the results of lower tier studies (adult honey bee

acute or al, chronic adult honey bee, acute and chronic larval), a field testing study may not be needed to complete the risk assessment for pollinators. A protocol should be submitted prior to test initiation.

850.3100 Earthworm

Subchronic Toxicity Test None N /A No Data have not been submitted to fulfill this guideline. A data gap was not identified as these data are not necessary for risk assessment at this time.Page 33 of 43 Table 9 . Available ecological effects data for terrestrial organisms exposed to imazapic and remaining data

gaps.

OCSPP Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed for risk assessment? Justification and Assumptions EPA

will Make in Absence of Data

850.4100 Seedling

Emergence and Seedling Growth 43320308 Supplemental ( Quantitative for 7 species

, Qualitative for
tomato, oats and ryegrass) Yes The current study is being downgraded due to the use of TGAI and the use of continuation tests in concert with a base test to determine NOAEC/IC 05 and IC 25 endpoints. EFED does not support combining the r esults of multiple studies for statistical analysis of assessment endpoints. Therefore, new seedling emergence data is requested for tomato, oat and ryegrass using a representative TEP.

850.4150 Vegetative

Vigor 43320309 Supplemental Qualitative for
6 species, Invalid for
corn, oats, onion and tomato). Yes The current study is being downgraded due to the use of TGAI and the use of continuation tests in concert with a base test to determine NOAEC/IC 05 and IC 25 endpoints. EFED does not support combinin g the results of multiple studies for statistical analysis of assessment endpoints. Therefore, new vegetative vigor data is requested on the entire suite of 10 species using a representative TEP.



## 12. References

ENSR, 2005. Imazapic Ecological Risk Assessment Final Report. Prepared for the USDI BLM, Nevada State Office, Reno, Nevada. November, 2005. ENSR Document Number 09090

- 020

- 650.

SERA (Syracuse Research Corporation), 2004. Imazapic

— Human Health and Ecological Risk
Assessment

— Final Report. Prepared for the USDA Forest Service, Forest Health Protection. Syracuse, New York. December 23, 2004. SERA TR 04

- 43

- 17

- 04b

USEPA, 2014a. BEAD Chemical Profile for Registration Review: Imazapic (129041) and Imazapic

- ammonium (128943) . Office of Pesticides Program, Biological a nd Economic Analysis Division. Arlington, VA. July 10, 2014Page 34 of 43

USEPA, 2014b. Registration Review Problem Formulation for Imazethapyr and Imazethapyr
Ammon ium Sal t. D415245. Office of Pesticide Program, Environmental Fate and Effects Divis ion. Arlington, VA.

USEPA, 2014c. Guidance for Assessing Pesticide Risks to Bees. Office of P esticide Programs, USEPA, Washington D.C. Health Canada Pest Managem ent Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, Sacramento, CA. June 23, 2014.

USEPA, 2001 a . Imazapic. Results of the Health Effects Division (HED ) Metabolism Assessment Review Committ ee (MARC) Meeting Held on 22

- MA Y

- 2001. Chemical#s 128943 & 129041. Barcode D275136. Case 291904. Submission 8581930. Office of Pesticides Program, Health Effects Division, Arlington, VA. J une 7, 2001.

USEPA, 2001b. Imazapic (Chemical 129041): Amer ican Cyanamide Company; Section 3 review for use of imazapic herbicide (Plateau DG) to control weeds in pasture, rangeland, and the Conservation Reserve Program; D277341. Office of Pesticides Program, Environmental Fate and Effects Di vision, Arlington, VA. Oct. 15 , 2001

USEPA, 2001. Correction of estimated & water concentration from FIRST (DP Barcode D267288, dated May 10, 2001). D267228A. Office of Pesticides Program, E nvironmental Fate and Effects Di vision, Arlington, VA. May 28, 2001

USEPA, 2001. Imaza pic Section 3

- Pasture and Rangeland Use Tier 1 Water Assessment. D267228. Office of Pesticides Program, E nvironmental Fate and Effects Di vision , Arlington,
VA. May 10, 2001.

USEPA, 1999. Imazapic: Rate of Dissipation of CL 263222 Residues in Soil after Treatment with CADRE@ DG Peanut Herbicide Applied Postemergence to Peanuts in Georgia (MRID: 4483 1801). D256957. Office of Pesticides Program, E nvironmental Fate and Effects Di vision, Arlington, VA. June 28, 1999.

USEPA, 1995. The Ecological Effects Bra nch's (EEB) environmental risk assessment for the use of the imidazolinone type herbicide CADRE on peanuts

--- (Chemical Code 128943): DP Barcode D209889 and D209896. Office of Pesticides Program, Environmental Fate and Effects Division , Arlington, VA. Aug 25 , 1995.Page 35 of 43



### Appendix A . Screening Level Models to Evaluate Potential Importance of Drinking Water and Inhalation Exposure Pathways

SIP ( Screening Imbibition Program, v1.0) Inputs and Conclusions

Table 1. Inputs
Parameter Value
Chemical name Imazapic Solubility (in water at 25 o C; mg/L) 518000

Mammalian LD 50 (mg/kg

- bw) 5000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 20000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2150 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 538 Bobwhite quail NOAEC (mg/kg

- diet) 1187 NOAEC (mg/kg

- diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian sp ecies

Table 2. Mammalian Results
Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 89096.0000 89096.0000 Adjusted toxicity value (mg/kg

- bw) 3845.8028 15383.2113 Ratio of exposure to toxicity 23.1671 5.7 918Page 36 of 43

Conclusion* Exposure through drinking water alone is a potential concern for mammals Exposure through drinking water alone is a potential concern for

mammals

Table 3. Avian Results
Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 419580.0000 419580.0000 Adjusted toxicity value (mg/kg

- bw) 1548.9235 26.6916 Ratio of exposure to acute toxicity 270.8849 15719.5765

Conclusion* Exposure through drinking water alone is a potential concern for

birds Exposure through drinking water

alone is a potential concern for

birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking w ater may contribute to a total exposure that has potential for effects to non

- target animals.Page 37 of 43



### Appendix B

. Predictive Data for Parent Imazapic and its Degradates from QSAR Modeling using Ecosar v1.11 All values are in ppm ND = No empirical Data
NP = No prediction made for this class.

Red highlighted cells indicate poor agreement ( i.e. > 10x difference) between empirical data and predicted values. Yellow highlighted cells indicate reasonable agreement ( i.e. between 5x and 10x difference) between e mpirical data and predicted values.
Green highlighted cells indicate good agreement ( i.e. <5x difference) between empirical data and predicted values.

The empirical EC 50 for green algae was nondefinitive with no effects found at the limit dose of 0.0523 p pm. However, since the level of predicted toxicity is 6 orders of magnitude higher than the tested doses, it is unclear how well the model predicts the actual toxicity of parent imazapic and therefore the QSAR approach should not be used in risk assessmen t to evaluate the toxicity of imazapic metabolites to green algae.

Green Algae EC50 Empirical EC50 Amides

--

acid Neutral

Organic
Parent >0.0523 23147 1110
268,407 ND NP 1617

290,610 ND 226 1062 290,811 ND NP 769
2

- carbamoyl

- 5

- methyl

- nicotinic acid ND 199 973

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (2

- ring structure) ND NP 2122

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structure) ND NP 528

The empirical NOAEC for green algae is 5 orders of magnitude below the predicted toxicity using the amides an d ne utral organic chemical classes. Therefore, it is unclear how well the model predicts the actual toxicity of parent imazapic and therefore the QSAR approach should not be used in the risk assessment to evaluate the toxicity of imazapic metabolites to gr een algae.

Green Algae NOAEC Empirical NOAEC Amides

--

acid Neutral

Organic
Parent 0.0523 115 212 268,407 ND NP 362
290,610 ND 114 206Page 38 of 43

290,811 ND NP 145.8

2

- carbamoyl

- 5

- methyl

- nicotinic acid ND 90.3 179

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (2

- ring st ructure) ND NP 349

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structure) ND NP 104

The empirical EC 50 for daphnids was nondefinitive with no effects found at the limit dose of 100 ppm. Since, the level of predicted toxicity was 1

- 2 orders of magnitu de higher than the tested doses, it is unclear how well the model predicts the actual toxicity of parent imazapic and therefore the QSAR approach should not be used in the risk assessment to evaluate the toxicity of imazapic metabolites to freshwater inver tebrates on an acute basis.

Daphnid EC50 Empirical EC50 Amides

--

acid Neutral

Organic
Parent > 100 23,147 2681

268,407 ND NP 2910

290,610 ND 21387 2500 290,811 ND NP 1880

2

- carbamoyl

- 5

- methyl

- nicotinic acid ND 22300 2520

2

- carbamoyl

- 5

- methyl

- 3

- nicoti nic acid (2

- ring structure) ND NP 6800

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structure) ND NP 1205

The empirical NOAEC for daphnids is less than 5x more sensitive than the predicted toxicity from the Amides

- acid and Neutral Organic Chemical Stru cture Classes. This indicates that there is relatively good agreement between the modeled values and the empirical data. Imazapic degradates were predicted to have similar toxicity as parent imazapic. 2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structu re) was predicted to be twice as toxic as parent imazapic, but considering these predicted values are approximately 4

- 5 orders of magnitude greater than the maximum EECs from previous assessments, it is considered unlikely that empirical data for this degr adate would have much value for the risk assessment to evaluate chronic effects of imaza picPage 39 of 43

to freshwater invertebrates or that this degradate would contribute greatly to risk conclusions for imazapic.

Daphnid NOAEC Empirical NOAEC Amides

--

acid Neutral

Or ganic
Parent 96 470 176

268,407 ND NP 233
290,610 ND 454 167 290,811 ND 122

2

- carbamoyl

- 5

- methyl

- nicotinic acid ND 401 158

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (2

- ring structure) ND NP 370

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structure) N D NP 82

There was 10% mortality at the limit concentration of 100 ppm for the acute fish study. Since, the level of predicted toxicity was 1

- 2 orders of magnitude higher than the tested doses, it is unclear how well the model predicts the actual toxicit y of parent imazapic and therefore the QSAR approach should not be used in the risk assessment to evaluate the toxicity of imazapic metabolites to freshwater fish on an acute basis.

Fish LC50 Empirical EC50 Amides

--

acid Neutral

Organic
Parent > 100 1035 0 5441 268,407 ND NP 5500 290,610 ND 9866 5041 290,811 ND NP 3828

2

- carbamoyl

- 5

- methyl

- nicotinic acid ND 9160 5200

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (2

- ring structure) ND NP 14700

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structure) ND NP 241 5

The empirical NOAEC is less than 5x more sensitive than the predicted toxicity from the Neutral Organic Chemical Structure Class but >10x less sensitive than the predicted toxicity from the Amides

- acid Chemical Structure Class. This indicates that the re is relatively good agreement between the modeled values for the Neutral Organic Chemical class and the empirical data.Page 40 of 43

Imazapic degradates were predicted to have similar toxicity as parent imazapic. 2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring structu re) was predicted to be >2x more toxic than parent imazapic, but considering these predicted values are approximately 5 orders of magnitude greater than the maximum EECs from previous assessments, it is considered unlikely that empirical data for this degr adate would have much value for the risk assessment to evaluate chronic effects of imazapic to freshwater invertebrates or that this degradate would contribute greatly to risk conclusions for imazapic.

Fish NOAEC Empirical

NOAEC Amides

--

acid Neutral

Organ ic
Parent 96 7.11 450 268,407 ND NP 495 290,610 ND 7.06 420 290,811 ND NP 315

2

- carbamoyl

- 5

- methyl

- nicotinic acid ND 5.64 422

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (2

- ring structure) ND NP 1120

2

- carbamoyl

- 5

- methyl

- 3

- nicotinic acid (1

- ring

structure ) ND NP 203Page 41 of 43



### Appendix C

. Data Justification Tables for Non

- guideline Studies

Guideline Number: Non

- Guideline Study Title: Adult Honey Bee Acute Oral Toxicity
Rationale for Requiring the Data This study is needed for the assessment to evaluate risks to honey bees if the registered uses will result in bee exposure. Imazapic uses include aerial applications to pastures, rangeland, agricultural fallow/idleland/conservation reserve, conifer plantations, forest trees, and nonagricultural uncultivated

are as/soils where spray drift may land on blooming non

- target plants and result in residues in polle n and nectar which could then be transported to colonies where in

- hive bees including young adult and developing brood ( i.e. , eggs, larvae and pupae) may be ex posed. Therefore, exposure at all bee life stages would be expected.

T he Agency has recently finalized its framework to assess risk to pollinators ( USEPA, 2014 c ). EPA now requires this study for all use sites where potential exposure to pollinators ma y occur. Registrants may request a waiver of the study if use practices significantly restrict exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study, the Organization for Economic Cooperation and Development (OECD) h as developed a formal test guideline for an acute oral toxicity study with adult honey bees (OECD TG213) that may be used to assess the acute oral exposure pathway for adult bees.
Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision

- making?

The acute oral toxicity study with adult bees provides median lethal dose (LD 50 ) value for honey bees ( A. mellifera ) based on acute oral exposure. These data are used in conjunction with acute contact LD 5 0 data obtained through OCSPP 850.3020 to estimate the acute toxicity of technical grade active ingredient (TGAI) to individual young adult honey bees. The studies also provide slopes for the dose

- response curves that can in turn be used for estimating th e likelihood of individual effects and sublethal effects observed in the study will be used to further characterize effects observed following a single exposure to the technical grade material. Data obtained from this study will be used in estimating acut e risk to individual adult bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

These data are needed for the registration review ris k assessment and for future endangered species assessments. The data would allow the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of imidazolinone

- class chemicals. This data may help the Agen cy determine whether any mitigations are needed. If the registration review and any future endangered species risk assessments are performed without these data, the Agency would have to assume that imidazolinone

class chemicals "may affect" insects, incl uding bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of imazapic might need to be restricted in areas where pollinators could be exposed.Page 42 of 43

Guideline Number: Non

- Guideline Study Title: Adult Honey Bee Chronic Oral Toxicity
Rationale for Requiring the Data This study is needed for the assessment to evaluate risks to honey bees if the registered uses will result in bee exposure. Imazapic uses include aerial applications to pastures, rangeland, agr icultural fallow/idleland/conservation reserve, conifer plantations, forest trees, and nonagricultural uncultivated areas/soils where spray drift may land on blooming non

- target plants and result in residues in pollen and nectar which could then be transpo rted to the colony where in

- hive bees including young adult and developing brood ( i.e. , eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life stages would be expected and may extend for chronic exposures since imazapic is relatively persistent except from degradation through aqueous photolysis

.

The Agency has recently finalized its framework to assess risk to pollinators (USEPA, 2014 c ). EPA now requires this study for all use sites where potential exposure to pollinators may occur . Registrants may request a waiver of the study if use practices significantly restrict exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study and OECD has yet to finalize test guidance for chronic studies, efforts a re currently underway to develop standardized guidelines for assessing effects from chronic (10

- day) exposures to adult bees in the laboratory.
Practical Utility of the Data
How will the data be used and how could the data impact the Agency’s future de cision

- making?

The 10

- day toxicity study with young adult bees provides no

- observed adverse effect level (NOAEL) and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Data obtained from this study will be used in estimating chro nic risk to individual adult bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

These data are needed for the registration review r isk assessment and for future endangered species assessments. The data would allow the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of imidazolinone

- class chemicals. This data may help the Ag ency determine whether any mitigations are needed. If the registration review and any future endangered species risk assessments are performed without these data, the Agency would have to assume that imidazolinone

- class chemicals "may affect" insects, i ncluding bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of imazapic might need to be restricted in areas where pollinators could be exposed.

Guideline Number: Non

- Guideline Study Title: Larval H oney Bee Acute and Chronic Oral Toxicity
Rationale for Requiring the Data These studies are needed for the assessment to evaluate risks to honey bees if the registered uses will result in bee exposure. Imazapic uses include aerial applications to pastur es, rangeland, agricultural fallow/idleland/conservation reserve, conifer plantations, forest trees, and nonagricultural uncultivated areas/soils where spray drift may land on blooming non

- target plants and result in residues in pollen and

nectar that can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood ( i.e. , eggs, larvae and pupae) may be exposed. Therefore, exposure at all be e life stagesPage 43 of 43

Guideline Number: Non

- Guideline Study Title: Larval H oney Bee Acute and Chronic Oral Toxicity
Rationale for Requiring the Data would be expected and may extend for chronic exposures since im azapic is relatively persistent except from degradation through aqueous photolysis.

T he Agency has recently finalize d its framework to assess risk to pollinators ( USEPA, 2014c ). EPA now requires these studies for all use sites where potential exposure to pollinators may occur. Registrants may request a waiver of the studies if use practices significantly restrict exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study, the 21

- day larval toxicity study currently und er development by OECD potentially provides acute as well as chronic oral toxicity endpoints on developing bee brood and (when this guidance is finalized) may be used to satisfy the requirement for both acute and chronic oral toxicity to honey bee larvae. Registrants are at liberty though to submit a separate acute (single dose) larval toxicity study following OECD TG 237 as well as the 21

- day repeat dose chronic toxicity study.
Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision

- making?

The 21

- day larval toxicity study under development by OECD provides both acute and chronic toxicity data on developing bee brood and will yield a median lethal dose (LD 50 ) for assessing acute toxicity during the early part of the study as well as a 21

- day no

- observed adverse effect level (NOAEL) and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Effects on survival and development (adult bee

e mergence) from repeat exposures to the active ingredient will be used in estimating chronic risk to individual brood. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are nee ded at the whole colony level.

These data are needed for the registration review risk assessment and for future endangered species assessments. The data would allow the Agency better characterize the potential for risk to insects (including beneficial po llinators) from the use of imidazolinone

- class chemicals. This data may help the Agency determine whether any mitigations are needed. If the registration review and any future endangered species risk assessments are performed without these data, the Agen cy would have to assume that imidazolinone

class chemicals "may affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of imazapic might need to be restricted in areas where pollin ators could be exposed.