Page 1 of 3 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

PC Code s : 128840 , 128848 DP Barcode: D418728 Date: September 10 , 2014

MEMORANDUM

SUBJECT: Registration Review: Preliminary Problem Formulation for Environmental Fate,

Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for Imazaquin and the Ammonium Salt of Imazaquin

TO : Wilhelmena Livingston , Chemical Review Manager

Tom Myers, Team Leader Kevin Costello , Branch Chief Pesticide Re

- evaluation Division (PRD 7508P)

FROM: Andrew Sayer, PhD, Biologist

J a m es N. Carleton, PhD, Senior Fate Scientist ERB IV / EFED (7507P)

THROUGH: Chuck Peck, Environmental Engineer

Thomas Steeger, PhD, Senior Science Advisor ERB IV / EFED (7507P)

APPROVED Sarah Winfield

, Acting Branch Chief BY: ERB IV / EFED (7507P)

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the environmental fate, ecological risk, endangered species, and drinking water exposure assessments to be conducted as part of the Registration Review of imazaquin and the ammonium salt of imazaquin (CAS numbers 81335

- 37

- 7 and 81335

- 47

- 9, respectively; PC Code s 128848 and 128840, respectively )

. The problem formulation describes the preliminary ecological risk hypothesis and analysis plan for evaluating and characterizing risk to non

- target species in support of the Registration Review of imazaquin and its ammonium salt . ThisPage 2 of 3

document also recommends studies that shoul d be included in a generic data call

- in (DCI) to address uncertainties surrounding the environmental fate and potential ecological effects of imazaquin and its ammonium salt

.
Because the ammonium salt of imazaquin dissociates in water t o form the carbox ylate anion

, “imazaquin” will be used to refer to both imazaquin and its ammonium salt. Both the ammonium salt and its carboxylate anion will be considered in this assessment

. Four major photolytic degradates have been determined by HED to have the poten tial for toxicity equivalent to that of the parent

. Because of the paucity of acceptable studies a large compliment of environmental fate data are recommended

, and pending the submission and review of these (and additional ecotoxicity) data, one or more of these degradates may also be considered to be of
concern to non

- human biological receptors . We will re

- evaluate degradates of concern for the ecological risk assessment once the se additional data have been submitted and reviewed.

The fate database is incomplete based on the environmental fate data requirements outlined in the Code of Federal Regulations Title 40 Part 158 (40CFR158) Subpart N 1

. Environmental fate data gaps include :

 § 835.1230 Batch equilibrium adsorption / desorption

 §835.2410 Photodegradation on soil

 §835.2240 Photodegradation in water

 § 835.4100 Aerobic soil metabolism ( three additional soils)

 §835.4300 Aerobic aquatic metabolism

 §835.4400 Anaerobic aquatic metabolism

 §850.6100 Environmental Chemistry Methods (ECM) and Associa ted Independent Laboratory Validations (ILV) for residues in water

The ecological database is also incomplete based on the ecological effects data requirements outlined in the 40CFR158 Subpart G 2

. Ecotoxicology data gaps 3 include :

 Aquatic:

o § 850.1025, § 850.1035, § 850.1045, or § 850.1055 Saltwater invertebrate acute toxicity

o § 850.1075 Saltwater fish acute toxicity

o § 850.1300 Freshwater invertebrate life

- cycle

o § 850.1350 Saltwater invertebrates life

- cycle

o § 850.1400 Freshwater fish early

- life stage

o § 850.1400 Saltwater fish early

- life stage

o § 850.4400 Aquatic plant growth: Tier II vascular plants

o § 850.4500 Aquatic plant growth: Tier II algae (3 species)

o § 850.4550 Aquatic plant growth: C yanobacteria

1 CFR. 2013. Title 40 (Protection of the Environment), Chapter 1 (Environmental Protection Agency), Subchapter E (Pesticide Programs), Part 158 (Data Requirements for Pesticides), Subpart N (Environmental Fate) http://www.ecfr.gov/cgi

- bin/text

idx?c=ecfr&SID=ff5c7fef3645e7cd5abceca0b597bccb&tpl=/ecfrbrowse/Title40/40cfr158_main_02.tpl

2 CFR. 2013. Title 40 (Protection of the Environment), Chapter 1 (Environmental Protection Agency), Subchapter E (Pesticide Programs), Part 158 (Data Requirements for Pesticides), Subpart G (Ecological Effects) http://www.ecfr.gov/cgi

- bin/text

idx?c=ecfr&SID=ff5c7fef3645e7cd5abceca0b597bccb&rgn=div6&view=text&node=40:25.0.1.1.9.7&idno=40

3 A complete listing of all the environmental fate and ecoto xicology data gaps

, along with justification according to 40 CFR, Part 158

- Subpart G

, are listed in Section 9 of this document.Page 3 of 3

 Terrestrial

o §850.2300 Avian reproduction (upland game species an d waterfowl)

o OECD Guideline 237 and Non

- Guideline : Honey bee larval acute and chronic oral toxicity

o Non

- guideline: Honey bee adult acute and chronic oral toxicity

In the absence of the above toxicity data, major uncertainties in the assessment of imazaquin include the potential for risk to the following taxa: non

- target aquatic fish and aquatic invertebrates (chronic exposure), aquatic vascular and nonvascular plants, and birds (chronic exposure)

.Page 1 of 35



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

the Ammonium Salt of Imazaquin

Imazaquin
CAS: 81335

- 37

- 7 PC Code: 128848 

### Ammonium Salt of Imazaquin
CAS: 81335

- 47

- 9 PC Code: 128840

Prepared by: Andrew Sayer, Ph.D., Biologist Jim Carleton, Ph

. D., Senior Fate Scientist U.S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch IV 1200 Pennsylvania Ave., NW Mail Code 7507 Washington, DC 20460 Reviewed by: Charles Peck, Environmental Engineer Thomas Steeger, Ph.D., Senior Advisor

September 10, 2014Page 2 of 35 

### T ABLE OF 

### C ONTENTS

1. EXECUTIVE SUMMARY

................................ ................................ ................................ .... 3 2. INTRODUCTION

................................ ................................ ................................ .................. 3 3. USE/USAGE CHARACTERIZATION

................................ ................................ ................. 4 4. CONCLUSIONS FROM PREVIOUS ASSESSMENTS

................................ ....................... 5 4.1. Drinking Water Assessment

................................ ................................ ............................. 5 4.2. Clean Water Act Programs

................................ ................................ ............................... 6 5. ENVIRONMENTAL FATE AND TRANSPORT

................................ ................................ . 7 6. RECEPTORS

................................ ................................ ................................ .......................... 8 6.1. Effects to Aquatic Organisms

................................ ................................ .......................... 9 6.2. Effects to Terrestrial Organisms

................................ ................................ ...................... 9 6.3. Ecological Incidents

................................ ................................ ................................ ....... 10 6. 3.1. Ecological Incident Information System

................................ ................................ ..... 10 6.3.2. Avian Monitoring System

................................ ................................ ............................ 11 6.3.3. Aggregate Incident Database

................................ ................................ ..................... 11 7. EXPOSURE PATHWAYS OF CONCERN

................................ ................................ ........ 11 8. ANALYSIS PLAN

................................ ................................ ................................ ............... 12 8.1. Stressors of Concern

................................ ................................ ................................ ....... 12 8.1.1. Ecological Risk Assessment

................................ ................................ ........................ 12 8.1.2. Drinking Water Assessment

................................ ................................ ........................ 13 8.2. Measures of Exposure

................................ ................................ ................................ .... 13 8.3. Measures of Effect

................................ ................................ ................................ ......... 14 8.4. Endangered Species Assessments

................................ ................................ .................. 14 8.5. Endocrine Disruptor Screening Program (EDSP)

................................ .......................... 15 9. PRELIMINARY IDENTIFICATION OF DATA GAPS

................................ ..................... 15 9.1. Environmental Fate

................................ ................................ ................................ ........ 15 9.2. Effects

................................ ................................ ................................ ............................. 16 10. REFERENC ES

................................ ................................ ................................ .................. 23 Appendix A. BEAD Chemical Profile 1

................................ ................................ ........................ 25 Appendix B. Submitted Environmental Fate and Ecological Effects Studies

.............................. 26 Appendix C. EIIS Incidents

................................ ................................ ................................ .......... 29 Ap pendix D. Aggregate Incident Reports for Imazaquin and the Ammonium Salt of Imazaquin 30 Appendix E. SIP Results for Evaluate Pot ential Risk to Birds and Mammals from Drinking Water Exposure

................................ ................................ ................................ ............................. 32 Appendix F. STIR Results to Evaluate the Potential for Inhalati on Risk to Birds and Mammals

................................ ................................ ................................ ................................ ....................... 33 Appendix G. Chemical structures of imazaquin and identified major photodegradates

.............. 34Page 3 of 35

1. EXECUTIVE SUMMARY

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the R egistration R eview of imazaquin ( PC code 128848 ; CAS No. 81335

- 37

- 7 ) and the ammonium salt of imazaquin ( PC code 128840 ; CAS No. 81335

- 47

- 9 )

. Unless otherwise specified, references to imazaquin throughout this document include imazaquin and its ammonium salt

. The problem formulation describes the methods planned for the completion of drinking water and ecological risk assessments and provides a n overview of the environmental fate, ecological effects, and potential risks associated with the use of imazaquin . The problem formulation also addresses uncertainties unique to the risk assessment of imazaquin . This document identifies additional studi es for both ecological effects and environmental fate that would be beneficial to the conduct of an ecological risk assessment ; see Section 9 for a dditional details and explanation. Unless otherwise noted, studies are requested for imazaquin ( PC code 128848 )

.
Imazaquin is a n herbicide for use primarily on soybeans. According market research surveys

, imazaquin usage on soybeans in the U.S. dec reased by several fold between 1998 and about 2003, then remained roughly steady through 2012 (USEPA, 2014b )

. Based on available data it is generally non

- toxic to most taxa ( i.e., freshwater fish, freshwater invertebrates, birds and mammals). Data are pe nding review for plants where toxic effects would be expected. The Agency has recently posted new guidance for assessing risks of pesticides to bee s 4 . Because of this, a suite of tests is recommended for evaluating the potential toxicity of imazaquin to bees. Based on model information, imazaquin is highly mobile (K oc = 17.5 L/kg oc ), persistent under most conditions (stable to hydrolysis and anaerobic aquatic degradation; aerobic soil t 1⁄2 = 630 days; aerobic aquatic t 1⁄2 = 1260 days), but labile to aqueous photolysis (t 1⁄2 <1day)

.

2. INTRODUCTION

Imazaquin is a broad spectrum herbicide registered as a preplant, preemergence, and early
pos temergence herbicide for use primarily on soybeans. It is also registered for pre

- and postemergence weed control on ornamentals and warm season turf grass in both residential and

non

- residential settings. It is also used on turf in both commercial and residential settings and on ornamental trees, shrubs, and groundcover. Similar to other imidazolinone herbicides, i maz aquin is likely systemic

, i.e

., it is absorbed by both roots and foliage and translocated via both xylem and phloem tissues of the plant . It may be transported to regions of the plant where growth can take place.

Imazaquin is used mainly across the centra l Midwest from Kentucky to Illinois and across the mid

- South in Arkansas, Louisiana and Mississippi . It is an imidazolinone herbicide which controls weeds by inhibiting the synthesis of specif ic amino acids necessary for plant growth.

4 USEPA. 2014. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs. United States Environmental Protection Agency. Available at http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/Guidance AssessingPesticideRisk2Bees.pdfPage 4 of 35

3. USE /USAGE CHARACTERIZATION

Based on information provided in the Biological and Economic Analysis Division (BEAD) C hemical Profile (BCP : USEPA

, 2014 b ) for Registration Review, i mazaquin is commonly formulated as water dispersible gran ules, wettable powders, soluble concentrates, and emulsifiable concentrates ( Table 1 )

. Both i mazaquin and its monoammonium salt can be applied using aerial or ground application. The BCP indicates that an average (presumably annual) of 5 6 ,000 lbs a.e. (acid equivalents) of imazaquin w as applied to soybeans in the U.S

. between 2008 and 2012. Registered a gricultural uses of i mazaquin and imazaquin monoammonium salt are limit ed to soybeans and sod farms. Registered n on

- agricultural uses include landscape ornamen tals, residential and commercial lawns and turf, and golf courses.

According to proprietary market research surveys

, imazaquin us ag e on soybeans in the U.S. ( in terms of both lbs a.e. applied and total area treated )

, dec reased by several fold between 1998 and about 2003, then remained roughly steady through 2012 ( USEPA, 2014 b )

. From 1998 to 2012

o n average 132,000 lb s a.e. w ere applied to 1

. 53 million acres each year , for an average annual application rate of 0.09 lbs a.e. per acre. Product

- specific usage data indicate the same trend s prevailed for both active ingredients ( i.e

., i mazaquin and its monoammonium salt )

. The states with the highe st usage in terms of percentage of total pounds a.e. applied nationally during the 2008

- 2012 time period were Indiana (37%), Ohio (33%), and Michigan (11 %)

. The average rates of application and number s of applications annually were similar among the se three major
usage states. Based upon available private market research survey data

, BEAD also reported 15,000 lbs of imazaquin was used (presumably annually) in the turf and ornamental m arket, includ ing 9,000 lbs a.e. applied by lawn care operators and 6,000 lbs a.e. applied to lan dscapes in

“ the most recent year available ” (presumably 2012)

. No other reports of imazaquin use wer e fo und for the nonagricultural market. The BCP , which can be found in Appendix A , lists the use patterns associated with the active registrations of imazaquin and the monoammonium salt of imazaquin

. EFED will rely on information in the BCP when estimating environmental exposures that result from these registered uses. I n order to fulfill its mandate of being protective, EFED will employ results of modeling scenarios that generate maximum exposure estimates ( i.e

., concentrations) amo ng registered uses, for both the drinking water and ecological risk
assessments. Any absence of information on the labels that specifies the maximum single application rate, the application interval, the annual maximum rate allowed (lbs a. e ./year), or
app lication method may result in conservative assumptions.

Table 1

. Imazaquin Use Table

Use(s) Active

Ingredient EPA

Registration Number(s) Application

Type/ Equipment Max.

Single Applicatio n Rate (lb

a. e . /A) Max #

Apps./yr Max #

Apps./CC Max.

Annual App. Rate (lb

a.e . /A ) Min

Retreatme nt Interval
Lawns (commercial/i ndustrial) Imazaquin 241

- 319 ground 0.4954 NS NS NS NS

Cottonwoods (forest/shelter belt) Imazaquin 241

- 306 aerial, ground 0.245 NS NS 0.245 NSPage 5 of 35

Golf course turf, sod farms, ornamental lawns, ornamental woody shrubs and vines, recreation area lawns Imazaquin 241

- 319 ground 0.4954 NS NS NS NS

Soybeans Imazaquin 241

- 376, 241

- 407, 241

- 415, 241

- 369, 241

- 306, 241

- 405, LA070001 aerial 0.1838 1 NS NS NS

Ornamental and/or shade

trees Imazaquin

ammonium salt 241

- 303 ground 1.1 NS NS NS NS

Ornamental lawns and turf, ornamentals unspecified Imazaquin

ammonium salt 73342

- 4 ground 0.3813 NS NS NS NS

Lawns and turf (ornamental) Imazaquin

ammonium salt 241

- 326 ground 0.4086 NS 2 NS NS

Ornamental woody shrubs and vines Imazaquin

ammonium salt 241

- 303 ground 1.1 NS NS NS NS

Soybeans Imazaquin

ammonium salt 5905

- 583 aerial, ground NS NS NS NS NS

Soybeans Imazaquin

ammonium salt 241

- 289, 241

-

307, 241

- 327 aerial,

ground 0.133 NS NS 0.2646 1 NS

1 241

- 289 only

4. CONCLUSIONS FROM PREVIOUS ASSESSMENTS

4.1. Drinking Water Assessment

An ecological risk assessment has not previously been conducted for imazaquin , although a Tolerance Reassessment and Risk Management Decision (TRED) was issued in 2005 (USEPA, 2005c)

. As discussed in the TRED, c oncentrations of imazaquin to which humans may be potentially exposed through ingestion of drinking water were assessed through evaluation s of surface water and groundwater monitoring data

, and via modeling (D313182 : USEPA 2005 a and USEPA 2005 b ) . Surface and groundwater monitoring data were available from the United States Geological Survey (USGS) National Water

- Quality Assessment (NAWQA) Program

, and from an additional USGS study on pesticide conc entrations in high

- use areas in the Midwest. Maximum concentrations of imazaquin in the monitoring data were 4.89 μg a

. e

. /L in surface water and 0.098 μg a

. e

. /L in groundwater (USEPA 2005)

. For a variety of reasons

, monitoring data are unlikely to captur e maximum historical concentrations, or to represent maximum potential future concentrations of most pesticides. T herefore

, m odeling is used by EFED to estimate concentrations expected to be representative of highly (though not necessarilyPage 6 of 35

maximally) vulnerable waters
, and monitoring data are used to further characterize actual measured concentrations in water

.

A June 2005 drinking water assessment (DWA) (D313182 : USEPA

, 2005 a ) was amended in September 2005 (D313182 : USEPA

, 2005 b ) to include four ma jor photolytic degradates of imazaquin identified in unbuffered, distilled water (3

- quinolinecarboxylic acid; 2,3 quinolinedicarboxylic acid imide; 2,3

- dihydro

- 3

- imino

- 1H

- pyrrolo

- [3,4b]quinolin

- 1

- one; and 2,3 quinolinedicarboxylic acid) that HED determine d to have the potential to be toxicologically equivalent to the parent compound (structures of these degradates and the parent compound are given in Appendix G ). Exposure m odeling was conducted employing an updated aquatic photolysis half

- life input that took into account the sum of parent imazaquin and these four degradates. Results for the use ( i.e. , turf, at 2 applications/year) that generated the highest estimated drinking water concentrations ( EDWCs ) are presented in Table 2

.

The E DW Cs in sur face water were generated using the Pesticide Root Zone Model ( PRZM ; version 3.12 ) coupled with the Exposure Analysis Model System ( EXAMS ; version 2.98.04 )

. EDWCs in groundwater were generated using the Screening Concentrations in Ground Water ( SCI

- GROW ; version 2.3) model

. C oncentrations are given in acid equivalents

, and represent total toxic residues, i.e

. , parent plus the four degradates of concern.

Table 2 . Imazaquin maximum E DW Cs , for use in human health drinking water
assessment

Use Surface water ( PRZM / EXAMS ) Groundwater ( SCI

- GROW )

Acute (Peak) Chronic

(Annual average) Acute & Chronic

Turf

- 2 app s at 0.63 lb a.e./A each (total residue) 21.8 μg a

. e

. /L 11.6 μg a

. e

. /L 31.1 μg a

. e

. /L

4.2. Clean Water Act Programs

Imazaquin i s not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 5 No Total Maximum Daily Load s (TMDL s ) or section 304(a) water quality criteria have been developed for imazaquin

. 6 A quatic benchmarks have been established for imazaquin and are available at http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm . Any data submitted or

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDESPage 7 of 35

otherwise located as part of the R egistration R eview process may be used to revise aquatic life benchmarks if applicable.

5. ENVIRONMENTAL FATE AND TRANSPORT

Very little acceptable environmental fate data exist for imazaquin ( Table 3 )

. Available f ate

s tudies were submitted in the early 1980s and well before the current O ffice of C hemical S afety and P ollution P revention fate study guidelines were adopted into practice. Even so, most submitted studies were, at the time of evaluation, found to be “invalid ”, “unacceptable”, or otherwise did not fulfill then

- existing EPA data requirements outlined under Title 40 Part 158 of the Code of Federal Regulations 7 . The only exceptions to this are the adsorption/desorption ( Guideline §835.1240; Acc. #146213), hydrol ysis ( Guideline §835.2120; Acc. #131546), and aerobic soil metabolism ( Guideline §835.4100; Acc. # 146211) studies. The adsorption/desorption study (Fung

, 1983 ; Acc. # 146213 ) was found to “partially fulfill” data requirements, with Freundlich K ads values stated in the DER as “ ranging from 0.03 in loamy sand to 0.41 in clay loam soil ” ( individual sorption coefficient s were not listed, and units were not stated, but were presumably L /kg ). The aerobic soil metabolism study provides information on a single s oil (sandy loam), with a half

- life stated simply as “ 6

- 9 months ” in the DER, without further explanation

. Degradates identified in this study included 2

- [(1

- carbamoyl

- 1,2

- dimethylpropyl)

- carbamoyl]

- 3

- quinolinecarboxylic acid (at 7.6% of applied radioact ivity (AR)), CO 2 (14.6% of AR), and six unidentified compounds totaling 11% of AR. Studies on soil photolysis ( Guideline §835.2410; Acc. #146210) and aqueous photolysis ( Guideline §835.835.2240; Acc. #146209) were determined to be “invalid” and to “ not fu lfill data requirements ”, respectively. I n both cases there was inadequate characterization of the light sources used, and in the case of the aqueous photolysis study, degradates in buffered solution

were not identified (although , as noted above, the foll owing four major degradates were identified in unbuffered, distilled water : 3

- quinolinecarboxylic acid; 2,3 quinolinedicarboxylic acid imide; 2,3

- dihydro

- 3

- imino

- 1H

- pyrrolo

- [3,4b]quinolin

- 1

- one; and 2,3 quinolinedicarboxylic acid ) . Despite the s e deficien cies, it may be noteworthy that very rapid degradation ( i.e ., half

- lives of less than 1 day) was reported in the aqueous photolysis study. A cursory review of fate properties of other imadazolinone herbicides ( e.g ., imazamox, imazapic, imazapyr) reveals that rapid degradation via photolysis in water (though not in soil) is apparently a consistent feature of chemicals in this class, as is relatively high mobility. Other imidazolinone herbicides also tend to be stable to hydrolysis, and to be relat ively resistant to aerobic and anaerobic metabolism ( i.e ., only slowly degrading) in both soil and water.

A DWA was conducted in 2005 (USEPA 2005 a and 2005b ). Despite the fate data weaknesses identified in the previous paragraph , modeling was conducted a ssum ing that imazaquin is highly mobile (K oc = 17.5 L/kg oc )

, persistent under most conditions ( stable to hydrolysis and anaerobic aquatic degradation; aerobic soil t 1⁄2 = 630 days ; aerobic aquatic t 1⁄2 = 1260 days ) , but labile to

7 CFR. 2014. Code of Federal Regulations Title 40 (Protection of Environment) Chapter 1 (Environmental Protection Agency), Subchapter E (Pesticide Programs), Part 158 (Data Requirements for Pesticides), Subpart N (Environmental Fate) 158.1300 Environmental Fate Data Requirements Table. http://www.ecfr.gov/cgi

- bin/text

idx?SID=fffb5e77bf66491652b21b33aed2a12d&node=40:25.0.1.1.9&rgn=div5#40:25.0.1.1.9.12.1.1 (last accessed 04/17/14).Page 8 of 35

aqueous photolysis (t 1⁄2 <1day)

. Maximum EDWCs from this modeling , for use by HED in human exposure assessment, are listed in Table 2

.

Table 3 . Chemical Properties and Environmental Fate Characteristics of Imazaquin

Parameter Value Description Source ( B ean or Acc. #)

Selected Physical/Chemical Parameters

Molecular Mass 311.3 g/mol

-- D197157

Molecular Formula C 17 H 17 N3O 3 -- D197157
Vapor pressure ( 60 °C) <10

- 7 torr

-- D197157

Aqueous solubility (mg/L) (2 5  C) 60

-- D197157

Log o ctanol

- to

- water partition coefficient ( log K OW ) (2 2 °C) 2.2

-- D197157

Persistence

Hydrolysis h alf

- life (25±1  C) Stable at pH 5 Stable at pH 7 169.8 days at pH 9 acceptable 131546

Aerobic Soil Metabolism half

- life (25±1°C) 6

- 9 months acceptable 146211

Mobility

Freundlich adsorption coefficients (K F ) 0.03 in loamy sand to 0.41 in clay loam soil partially fulfills data requirements 146213

6. RECEPTORS

Acute (short

- term) toxicity information for imazaquin is based on registrant

- submitted studies

. Reported ecological incidents associated with imazaquin are summarized below.

Tables 4 and 5 provide summaries of the aquatic and terrestrial taxonomic groups, respectively, and surrogate species tested to characterize the potenti al acute ecological effects of imazaquin

. Based on the available ecoto xicity information, imazaquin is practically non

- toxic to aquatic and terrestrial animals on an acute exposure basis

. However, n o chronic toxicity data are available for aquatic and terrestrial organisms. While no toxic effects were seen in honey bees ( Apis mellifera ) via the acute contact route of exposure, data are not available on the acute oral toxicity of imazaquin to honey bees. There is no information on the toxicity of imazaquin to aquatic vascular or nonvascular plants

.

A lthough no data ar e available on the toxicity of imazaquin to perching ( passerine ) bird s , the low sensitivity of b obwhite quail ( Colinus virginianus ) and mallard duck ( Anas platyrhynchus ) to imazaquin indicates that further testing on passerines is not needed at this time (USEPA 2014 a )

.

Two Tier II terrestrial plant studies

, i.e

., seedling emergence/seedling growth (Guideline §850.4100) and vegetative vigor (Guideline §850.4150 ) conducted with Scepter ®

, have beenPage 9 of 35

submitted to the Agency and are currently under review (MR IDs 45 0 11801 and 44996103

, respectively )

. Incident reports suggest th at terrestrial plants may be sensitive to imazaquin.

6.1. Effects to Aquatic Organisms

Table 4 . Summary of Aquatic Toxicity Studies for Imazaquin

Taxonomic Group Study

Type Surrogate Species Toxicity Value ( mg/L active ingredient ) Acute

Toxicity Classification Source

Freshwater fish 1 Acute Rainbow trout ( Oncorhynchus mykiss ) LC 50 = 280 Practically nontoxic MRID:

00131556 Acc. No. 00072012

Freshwater invertebrates Acute Water flea ( Daphnia magna ) LC 50 = 280 Practically nontoxic MRID:

00131557 Acc. No. 00072012

1 Freshwater fish may be used as surrogates for aquatic

- phase amphibians.

6.2. Effects to Terrestrial Organisms

Table 5 . Summary of Terrestrial Toxicity Studies for Imazaquin

Taxonomic Group Study

Type Surrogate

Species Toxicity Value

(units in active ingredient ) Acute

Toxicity Classification Source

Birds 1 Acute Mallard duck ( Anas platyrhynchus ) LD 50 > 2150 mg/kg bw Practically nontoxic MRID:

00131559 Acc. No. 00072012

Acute Bobwhite

quail ( Colinus virginianus ) LD 50 > 2150 mg/kg bw Practically nontoxic MRID:

00131558 Acc. No. 00072012

Sub

- acute dietary Bobwhite

quail ( Colinus virginianus ) LC 50 >5000 ppm Practically nontoxic MRID:

00131560 Acc. No. 00072012

Mallard duck ( Anas platyrhynchus ) LC 50 >5000 ppm Practically nontoxic MRID:

00131561 Acc. No. 00072012

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) LD 50 >5000 mg/kg bw

(Male & Female) Practically nontoxic Acc. No.

00073706

Acute Inhalation Laboratory rat

( Rattus norvegicus ) LC 50 > 5.0 mg/L NA Acc. No. 00073706Page 10 of 35

Taxonomic Group Study

Type Surrogate

Species Toxicity Value

(units in active ingredient ) Acute

Toxicity Classification Source

Insects Acute

contact Honey bee

( Apis mellifera L. ) LD 50 >100 μg/bee Practically nontoxic MRID:

00131562 Acc. No. 00072012

Terrestrial plants Seedling

Emergence NA In Review NA MRID: 45011801

Terrestrial plants Vegetative

Vigor NA In Review NA MRID: 44996103

NA: Not Applicable

1 Birds may be used as surrogates for terrestrial

- phase amphibians and reptiles.

6.3. Ecological Incidents

Three databases were searched for ecological incidents possibly associated with imazaquin : the Ecological Incident Information System (EIIS), the aggregate incident database, and t he Avian Incident Monitoring System (AIMS). The EIIS is an OPP database that houses ecological incidents that have been reported to the Agency (USEPA 2007 a ) . When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known or suspected of con tributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposure. The AIMS data base is administered by the American Bird Conservancy and contains publicly available data on reported avian incidents involving pesticides. Many of the incidents listed in this database are also in the EIIS. The aggregate incident reports provide counts of ecological incidents considered “minor.” These are reported to the Agency quarterly by registrants.

6.3.1. Ecological Incident Information System

EIIS contains 5 incidents for imazaquin, all of which involved damage to terrestrial plants (s ee Tables C

- 1 an d C

- 2 in Appendix C )

. Many of the incidents were attributable either to direct application of the imazaquin product or to spray drift. Four incidents were attributed to imazaquin proper and one was attributed to the ammonium salt of imazaquin. Of the inc idents associated with imazaquin proper , one was determined to be a registered use, one was a misuse ; for the remaining two incidents, it was not reported whether the incident was a result of a registered use or a misuse

. The c ertainty index for attributing the incidents specifically to imazaquin use ranged from “probable” to “possible” for all 4 incidents. The application method was spray in each incident, except for the one instance of soil incorporation from seed treatment (there is no longer a seed treatment registered use)

. For the ammonium salt of imazaquin

, the application method was spray, but the use method was unde ter mined

, and the certainty index was categorized as a “possible”.Page 11 of 35

Incident reports for non

- target organisms typical ly provide information only on acute mortality events and plant damage. Sub

- lethal effects in organisms such as abnormal behavior, reduced growth and/or impaired reproduction may not be readily apparent and may go unreported; therefore, a n absence of inci dent reports does not necessarily equate to an absence of incidents.

6.3.2. Avian Monitoring System

AIMS was searched on April 8, 2014 and revealed no avian incidents associated with imazaquin or the ammonium salt of imazaquin

.

6.3.3. Aggregate Incident Database

In addition to the incidents recorded in EIIS, registrants have reported minor imazaquin and/or ammonium salt of imazaquin incidents to the Agency in aggregate reports. Registrants reported 57 minor plant inciden ts with products registered containing imaz aquin ( Table D

- 1, Appendix D ). Registrants reported 19 minor plant incidents and 1 minor fish and wildlife incident with products registered containing the ammonium salt of imazaquin ( Table D

- 2, Appendix D ). Unless additional information to the contrary on these aggregated incidents becomes available, they will be assumed to be representative of registered uses of imazaquin in the risk assessment. As noted in the preceding section, t he number of incident reports cannot be considered as a comprehensive representation of all possible incidents that may have occurred as a result of the use of a pesticide. During the risk assessment associated with Registration Review of imazaquin

, these databases will be checked again

, and any new incidents will be evalua ted to determine if they represent current use patterns of imazaquin

.

7. EXPOSURE PATHWAYS OF CONCERN

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 include a source, a release mechanism, an environmental transport medium, a point of exposure for ecological rec eptors, and a feasible route of exposure.

The environmental fate properties of imazaquin indicate the following transport mechanisms for potential exposure to aquatic and terrestrial organisms:

 Direct contact

 Spray drift

 Runoff

 Consumption of contaminat ed food (sprayed food)

 Consumption of contaminated water

 Root uptake (plants)

For terrestrial organisms , the major routes of exposure to imazaquin are considered to be direct contact as a result of direct application and spray drift and dietary ingestion of plants, animals, and/or soil that have imazaquin residues as a result of direct application, spray drift, and runoff.Page 12 of 35

For aquatic animal spec ies, the major route of exposure to imazaquin is considered to be uptake via the respiratory surface (gills) or the integument from surface water/sediment that has imazaquin residues as a result of spray drift and runoff.

For terrestrial (upland and semi

- aquatic) non

- target plants, the major routes of exposure to imazaquin are considered to be direct contact as a result of direct application and spray drift and root uptake via treated soil or soil contaminated via spray drift and runoff.

For aquatic plant s, the major routes of exposure to imazaquin are considered to be uptake from surface water/sediment containing imazaquin residues as a result of spray drift, runoff, and leaching to groundwater from soil where such groundwater is used for irrigation purpo ses

.
Drinking water and inhalation exposure pathways were screened using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalational Risk) programs ; SIP and STIR are described in detail at: http://www.epa.gov/oppefed1/models/terrestrial/index.htm

. SIP results showed acute exposure to imazaquin through drinking water does not represent a potential concern for mammals or birds (LOC exceedances not expected). Data are insufficient to determine the likelihood of adverse effects to mammals and birds from chronic exposure to imazaquin through ingestion of drinking water

. ( Appendix E ). Modeling results using STIR indicate that exposure to imazaquin through inhalation is not likely to be significant for birds or mammals (no LOC exceedances are expected via this potential route of exposure ; Appendix F )

.

8. ANALYSIS PLAN

8.1. Stressors of Concern

I n order to address stressors of concern , the potential for adverse effects on the environment from
exposure is estimated. The use, environmental fate, and ecological effects of imazaquin are characterized and integrated to assess the risks. This integration is accomplished using a risk quotient (ratio of exposure concen tration 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 advers e effect. However, as outlined in the Overview Document (USEPA 2004), the likelihood of effects to individual organisms from particular uses of imazaquin is estimated using the probit dose

- response slope and either the level of concern (discussed below) o r actual calculated risk quotient value. This 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 imazaquin

.

8.1.1. Ecological Risk Assessment

The stressors of concern are as follows:

 Terrestrial e nvironment: parent imazaquin and its ammonium salt

 Aquatic e nvironment: parent imazaquin and it s ammonium saltPage 13 of 35

 Drinking water: Four major photolytic degradates were determined by HED to have the potential for toxicity equivalent to that of the parent:

o 3

- quinolinecarboxylic acid

o 2,3 qu inolinedicarboxylic acid imide

o 2,3

- dihydro

- 3

- imino

- 1H

- py rrolo

- [3,4b]quinolin

- 1

- one

o 2,3 quinolinedicarboxylic acid)

Pending receipt of additional fate and ecotoxicity data, E FED may consider one or more of these degradates to also be stressors of ecological concern. Given the unacceptable status of many of the existing environmental fate studies, it is not possible to discount the possibility that additional, as

- yet unidentif ied degradates of concern may also be formed in the environment

.

8.1.2. Drinking Water Assessment

Despite the gaps in the fate database, previou s DWA s ( DP Barcode D313182) employed SCI

GROW and PRZM/EXAMS to estimate concentrations of imazaquin (parent and total toxic residues) in groundwater and surface water

, respectively. The Health Effects Division ( HED ) has determined that an updated DWA is needed to support future human health dietary risk assessments for imazaquin. The DWA will be revisi ted using the currently approved EFED tools PRZM

- Ground Water ( PRZM

- GW ) and Surface Water Concentration Calculator (SWCC), and employing conservative default inputs where appropriate in the case of missing fate data ( e.g ., aqueous photolysis). Any availab le monitoring data will be considered as well. Historically, t he stressor of concern for drinking water has been parent imazaquin plus four specific degradates (3

- quinolinecarboxylic acid; 2,3 quinolinedicarboxylic acid imide; 2,3

- dihydro

- 3

- imino

- 1H

pyrr olo

- [3,4b]quinolin

- 1

- one; and 2,3 quinolinedicarboxylic acid). A dditional environmental fate studies will be considered to determine whether additional degradates should be included in residues of concern

.

8.2. Measures of Exposure

EFED will use standard available models ( Table 5 ) to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

. Available monitoring data will also be considered.

Estimated concentrations of mobile and persistent herbicides, such as imazaquin , in irrigation water may be calculated to determine potential risk to irrigated crops. As detailed above, the persistence and mobility of imazaquin indicate the potential for the chemical to r each ground and surface water.

Because imazaquin is likely systemic, a pplications can result in absorption and translocation of ima zaquin throughout plant tissues . Birds, mammals, and terrestrial invertebrates may be exposed through ingestion of leaves, seeds, pollen, or other edible portions of plants . Leaves or other plant parts containing imazaquin residues may also fall to the g round or directly into water

, potentially resulting in post

- application releases of imazaquin to soil and /or water. S creening

level estimate s of exposure via such routes may be conduct ed as part of the preliminary
assessment for Registration Review

.Page 14 of 35

Aquatic exposure will be based on estimated environmental concentrations ( EECs ) in a waterbody that is considered vulnerable and presumed representative of ponds and low

- order
streams and will be generated using the EFED Surface Water Concentration Calcula tor (SWCC), which essentially implements current versions of PRZM and EXAMS

. Terrestrial exposure will be estimated using a model (TREX; version 1.5) that assumes direct applicat ion to a variety of avian and mammalian food items. Exposure to terrestrial plants will be estimated using a model (TerrPlant ; version 1.2) that assumes imazaquin drifts or moves with runoff to adjacent habitats. For more information on the various models that will be used in the risk assessment see the links as outlined in Table 6

.

Table 6

. List of the various models and the related taxa for which the models will be used.

Environment Taxa of

Concern Model (s) Link

Aquatic Fish/

Invertebrates /Plants SWCC (PRZM &

EXAMS) http://www.epa.gov/oppefed1/models/

water/

Terrestrial Vertebrate TREX (dietary item) http://www.epa.gov/oppefed1/models/t

errestrial/trex/trex_v1_5_2_webversi on .xlsm

Plant TerrPlant (Run

- off) http://www.epa.gov/oppefed1/models/t errestrial/index.htm#terrplant AgDRIFT (Spray drift) http://www.agdrift.com/AgDRIFt2/Do

wnloadAgDrift2_0.htm AGDISP (Spray drift) http://www.continuum

dynamics.com/pr

- agdisp.html

8.3. Measures of Effect

Toxi city data presented in Section 6 of this problem formulation will be used to calculate risk quotients. Any additional acceptable information submitted by the registrant or found in the open literature prior to conduct of th e risk assessment will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) (USEPA 2007 b ), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial pla nts, 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 adverse effects to species that are sensitive to the chemicals and from changes in structure a nd functional characteristics of the affected communities.

8.4. Endangered Species Assessments

Consistent 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 R egistration R eview

. The process for evaluating potential risks to listed species is further described at

: http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm

.Page 15 of 35

8.5. Endocrine Disruptor Screening Program (EDSP)

Imazaquin was not included in either the first group of 67 chemicals issued an order to conduct Tier 1 EDSP testing nor the second list of 109 chemicals

. For additional information the EDSP program, visit http://www.epa.gov/endo/

.

9. PRELIMINARY IDENTIFICATION OF DATA GAPS

9.1. Environmental Fate

Table 7 identifies environmental fate studies by Accession number 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 16 of 35

Table 7 . Submitted Environmental Fate Data for Imazaquin

OCSPP Guideline Data Requirement Submitted Studies (Accession #)* Study

Classification Are

additional data needed? Justification and

Assumptions EPA Will Make in the Absence of Data

835.2120 Hydrolysis 072014/131546 Acceptable No Submitted data were found acceptable.

835.2240 Aqueous Photolysis 073704/146209 Unacceptable Yes Required data for terrestrial food and non

- food use chemicals.

835.2410 Soil Photolysis 073704/146210 Invalid Yes Required data for terrestrial food and non

- food use chemicals.

835.4100 Aerobic Soil

Metabolism 073704/146211 Acceptable Yes Available study provides data for one soil (a sandy loam). Data are needed for three additional soils.

835.4300 Aerobic

Aquatic Metabolism NA Yes Required data for terrestrial food and non

- food use chemicals.

835.4400 Anaerobic Aquatic

Metabolism NA Yes Required data for terrestrial food and non

- food use chemicals.

835.4200 Anaerobic Soil

Metabolism 073704/146212 Invalid No Not needed if acceptable anaerobic aquatic data are submitted

.
835.1230/ 835.1240 Adsorption/

Desorption and Leaching 073704/146214 Partially fulfills data requirement Yes Required data for terrestrial food and non

- food use chemicals.

835.6100 Terrestrial

Field Dissipation 073704/131564 Does not fulfill data requirement No The combination of acceptable aerobic soil and soil photolysis studies, if submitted, should address any concerns regarding degradate formation and decline.
850.6100 ECM/ILV NA Yes
*W here two numbers are given, t he first number is the Accession number written on the DER itself. The second number is the number under which the DER is filed in Documentum.

9.2. Effects

Table 8 and 9 identify ecological effects studies for aquatic and terrestrial organisms, respectively, 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.

Table 8 . Submitted Aquatic Ecological Effects Data for Imazaquin

OCSPP Guideline Data

Requirement Submitted

Studie s (MRID) Study

Classifications Are additional

data needed? Justification and Assumptions

EPA Will Make in the Absence of Data

850.1010 Freshwater

invertebrate acute toxicity 00131557 Acceptable No NAPage 17 of 35

850.1025 850.1035 850.1045 850.1055 Saltwater

invertebrate acute toxicity None NA Yes No data are available with which

to assess acute risk to saltwater invertebrates. A cute toxicity data for estuarine/marine invertebrate s are required under 40 CFR, Part 158

- Subpart G to determine if ther e is a risk

concern. Data are required for one estuarine/marine invertebrate using TGAI 1

. 850.1075 Freshwater fish

acute toxicity 00131554 Acceptable No NA

00131555 Acceptable No NA

00131556 Acceptable No NA

850.1075 Saltwater fish

acute toxicity None NA Yes No data are available with which

to assess acute risk to saltwater fish. Acute toxicity data for estuarine/marine fish are required under 40 CFR, Part 158

- Subpart G to deter mine if there is a risk concern using TGAI 1

. 850.1300 Freshwater

invertebrate l ife

- cycle None NA Yes No data are available with which to assess chronic risk to freshwater invertebrates. C hronic toxicity data for freshwater invertebrates are required under 40 CFR, Part 158

- Subpart G to deter mine if there is a risk concern using TGAI 1

. 850.1350 Saltwater

invertebrates life

- cycle None NA Yes No data are available with which to assess chronic risk to saltwater invertebrates. C hronic toxicity data for saltwater invertebrates

are conditionally required under 40 CFR, Part 158

- Subpart G using TGAI 1 to determine if there is a risk concern. Data ar e required on estuarine/marine species if the product meets any of the following conditions: i) Intended for direct application to the estuarine or marine environment; ii) Expected to enter this environment in significant concentrations because of its expe cted use or mobility patterns; iii) If the acute LC 50 or EC 50 <1 mg/l; iv) If the estimated environmental concentration (EEC) in water is ≥0.01 of the acute EC 50 or LC 50Page 18 of 35 or if any of the following conditions exist: A) Studies of other organisms indicate th e reproductive physiology of fish and/or invertebrates may be affected. B) Physiochemical properties indicate bioaccumulation of the pesticide. C) The pesticide is persistent in water ( e.g ., half

- life in water > 4 days).

850.1400 Freshwater fish

early

- life stage None NA Yes No data are available with which to assess chronic risk to freshwater fish. C hronic toxicity data for freshwater fish are required under 40 CFR, Part 158

- Subpart G to determine if there is a risk concern using TGAI 1

. EFED recommends that the most sensitive species used to assess acute risk is utilized in the chronic toxicity test.

850.1400 Saltwater fish

early

- life stage None NA Yes No data are available with which

to assess chronic risk to saltwater fish. Estuarine/marine fish early life stage data are conditionally required under 40 CFR, Part 158

- Subpart G to determine if there is a risk concern using TGAI 1

. Data are required on estuarine/marine species if the product meets any of the following conditions: i) Intended for direct application to the estuarine or marine environment; ii) Expected to enter this environment in significant concentrations because of its expected use or mobility patterns; iii) If the acute LC 50 or EC 50 <1 mg/l; iv) If the estimated environmental concentration (EEC) in water is ≥0.01 of the acute EC 50 or LC 50 or if any of the following conditions exist: A) Studies of other organisms indicate the reproductive physiology of fish and/or invertebrates may be affected. B) Physio chemical properties indicate bioaccumulation of the pesticide. C) The pesticide is persistent in water ( e.g ., half

- life in water > 4 days).Page 19 of 35 1 TGAI=Technical Grade Active Ingredient; TEP=Technical End

- Use Product NA: Not Applicable

Table 9 . Submitted Terrestrial Ecological Effects Data for Imazaquin

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 00131559 Acceptable No NA 1

00131558 Acceptable NA 1

850.2200 Avian dietary

toxicity 00131560 Acceptable No NA

00131561 Acceptable

850.2300 Avian

reproduction None NA Yes No data have been submitted to

assess effects on avian reproduction. Avian reproduction stud ies are needed as part of the data set under 40 CFR, Part 158

- Subpart G to determine if there is a risk concern using TGAI 2

. 850.3020 Honey bee

acute contact toxicity 00131562 Acceptable No NA

OECD Guideline 237 and Non

Guideline: Honey bee

larval acute and chronic oral toxicity None NA Yes Although data for 850.3020 honey bee acute contact toxicity indicates imazaquin is practically

non

- toxic to honey bees, EFED has no data on the acute and chronic oral route of exposure. Therefore, data are needed to determine if there is an acute oral ris k to the honey bee using TGAI 2 ,3

. 850.4400 Aquatic plant

growth: Tier II vascular plants None NA Yes No data are available with which to assess risk to aquatic vascular plants. Toxicity data are needed under 40 CFR, Part 158

- Subpart G to determine if there is a risk

concern using TGAI or TEP 1

. 850.4500 (previously 850.5400) Aquatic Plant

Growth: Tier II algae None NA Yes Toxicity data on three species are needed under 40 CFR, Part 158

- Subpart G to determine if there is a risk concern using TGAI or TEP 1

. Tests with a freshwater diatom, marine diatom, freshwater green alga, and cyanobacterium are

reco mmended. 850.4550 Aquatic Plant

Growth: Cyanobacteria None NA YesPage 20 of 35

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

adult acute and chronic toxicity None NA Yes Similar to other imidazolinone herbicides, i mazaquin is a likely systemic herbicide. It is absorbed by both roots and foliage and translocated via both xylem and phloem. It may be transported to regions of the pl ant where growth can take place

. There may be a variety of opportunities for the herbicide to be applied when plants may be in bloom and attractive to pollinators. Therefore, this test is needed to evaluate the potential for direct and systemic exposures to larval be es using TGAI 2,3

. 850.4100 Terrestrial

plant toxicity: Seedling
emergence 45011801 NA No t at this time

– pending review Th e s e data are currently in

review. Studies establishing non

target plant toxicity for herbicides

are essential for establishing the extent of off

- site drift impacts

. 850.4150 Terrestrial

plant toxicity: Vegetative vigor 44996103 NA No t at this time

– pending review Th e s e data are currently in

review. Studies establishing non

target plant toxicity for herbicides

are essential for establishing the extent of off

- site drift /run

- off impacts

. 1 Although an acute oral study for a passerine species has not been submitted to the Agency, a data gap has not been identified at this time. Low avian toxicity (no mortality and no sublethal effects) was demonstrated in the submitted studies

. 2 TGAI=Technical Grade Active Ingredient; TEP=Technical End

- Use Product

3 Data on TEP is requ ired if the formulation may enhance s the toxicity of the chemical. NA: Not Applicable

EPA recently posted its guidance 8 for assessing risks of pesticides to bees and c onsistent with this guidance a suite of tests is recommended for evaluating the potential toxicity of pesticides to bees . Although data from the acute contact toxicity test (OCSPP 850.3020) with young adult honey bees (

Apis mellifera ) indicates imazaquin is practically non

- toxic to bees on an acute exposure basi s , there is uncertainty regarding the potential acute and chronic effects of the compound on honey bee larval development and survival as well as potential for chronic effects of adult bees . Similar to other imidazolinone herbicides, i mazaquin is a likely systemic herbicide. R esidues may be present in pollen and/or nectar and represent a route of exposure for bees through both contact and ingestion

. Therefore, additional data on pollinators is needed to fully characterize the risk associated with imazaquin use to all developmental stages of honey bees, as sensitivity may vary according to life

- stage and length of exposure (adult vs. larval and

8 USEPA . 2014. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs. United States Environmental Protection Agency. Available at http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/Guidance AssessingPesticideRisk2Bees.pdfPage 21 of 35

acute vs. chronic, respectively). As described in the guidance for assessing risks to bees, depending on the outcome of the screening

- level risk assessment, additional studies of bees at the colony level under semi

- and full

- field conditions may also be recomm ended.

Guideline Number: Non

- Guideline Study Title: Larval Honey Bee Acute and Chronic Oral Toxicity Rationale for Requiring the Data

These studies are needed to evaluate potential effects of technical grade active ingredient (TGAI) on honey bees

. Imazaquin is registered as a pre

- plant, pre

- emergence, and early post

- emergence broad spectrum herbicide for use soybeans, ornamentals, turfgrass, ornamental trees, shrubs, and groundcover where spray drift may land on blooming non

- target plants and result in residues in pollen and nectar (which could then be transported to the hive by forage bees ). Similar to other imidazolinone herbicides, i mazaquin is likely to be systemic. It is absorbed by both roots and foliage and can translocated via both xylem and phloem to pollen and/or nectar where it would represent a route of exposure to bees

. Residues 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.

The Agency finalized its framework to assess risk to pollinators 9 and recommends these studies for all use sites where potential exposure to pollinators may occur. Although EPA has not developed a guideline for this study, the 21

- day larval toxicity study currently under development by OECD 10 provides a draft guidance protocol for potentially assessing both the acute and chronic toxicity to developing brood (larvae and pupae) from repeat exposure pesticides. Registrants are at liberty though to submit a se parate acute (single dose) larval toxicity study following OECD TG 237 11 as well as the 21

- day repeat dose chronic toxicity study. For the chronic toxicity study though, since no guideline is available, a protocol is required to be submitted for EPA review and approval prior to study initiation. Practical Utility of the Data How will the data be used and how could the data impact the Agency’s future decision

- making?

The larval toxicity stud ies provide data on the effects of technical grade active ingredient (TGAI) on developing bees from acute (short

- term) and chronic (longer term) exposure and will be used for estimating risk to individual (solitary) bees as well as bee colonies (social 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 risk assessment s conducted in support of Registration Review as well as future endangered species assessments. Th e data would allow the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of imidazolinone

- class chemicals. Th ese data may help the Agency determine whether any mitigations are needed. If the R egi stration R eview 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, including bees and beneficial pollinators, directly (and endangere d species from other taxa indirectly), and uses of imazaquin might need to be restricted in areas where pollinators could be exposed.

9 USEPA et al .. 2014. Guidance for Assessing Pesticide Risks t o Bees. http://www2.epa.gov/sites/production/files/2014

- 06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf

10 OECD. 2013. OECD Draft Guidance Document Honey Bee ( Apis mellifera ) Larval Toxicity Test, Repeated Exposure. Revision of June 2013 draft GD, 25 November 2013. http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf

11 OECD. 2013. OECD Guidelines for the Testing of Chemicals Honey bee ( Apis mellifera ) larval toxicity test, single exposure. OECD/OCDE 237 Ad opted: 26 July 2013. http://www.oecd

ilibrary.org/docserver/download/9713171e.pdf?expires=1408719 503&id=id&accname=guest&checksum=9CA53CFD8192A7A5F5715D9D335 1A841Page 22 of 35

Guideline Number: Non

- Guideline Study Title: Adult Honey Bee Acute Oral Toxicity Rationale for Requiring the Data This study is needed to evaluate potential effects to honey bees from a single dose of technical grade active ingredient (TGAI)

. Imazaquin is registered as a pre

- plant, pre

- emergence, and early post

emergence broad spectrum herbicide for use soybeans, orn amentals, turfgrass, ornamental trees, shrubs, and groundcover where spray drift may land on blooming non

- target plants and result in residues in pollen and nectar (which could then be transported to the hive) or in direct contact with bees

.

Similar to other imidazolinone herbicides, i mazaquin is a likely systemic herbicide. It is absorbed by both roots and foliage and translocated to pollen and/or nectar via both xylem and phloem where it would represent a route of exposure to bees

. Residues 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. .

The Agency finalized its framework to assess risk to pollinators 12

. EPA now requires these studies for all use sites where potential exposure to pollinators may occur. Although EPA has not developed a guideline for this study, the Organization for Economic Cooperation and Development (OECD) has developed a formal test g uideline for an acute oral toxicity study with adult honey bees (OECD TG213 13 ) that may be used to assess the acute oral toxicity 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?

These data are used in conjunction with acute contact data obtained through OCSPP 850.3020 14 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 the likelihood of individual effects and sublethal effects observed in the study will be used to further chara cterize effects observed following a single exposure to the technical grade material. Data obtained from this study will be used in estimating acute risk to individual adult bees. Risk estimates based on these data will be considered along with other lin es of evidence to determine whether higher

- tier studies are needed at the whole colony level.

These data are needed for risk assessment s written in support of Registration Review as well as for future endangered species assessments. The se data would allo w the Agency to better characterize the potential for risk to insects (including beneficial pollinators) from the use of imidazolinone

- class chemicals. Th e s e data may help the Agency determine whether any mitigations are needed. If the R egistration R eview 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, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of imazaquin might need to be restricted in areas where pollinators could be exposed.

12 Ibid USEPA et al . 2014.

13 OECD. 1998. OECD Guidelines for the Testing of Chemicals Honeybees, Acute Oral Toxicity Test. OECD/OCDE 213 Adopted 21 st September 1998. http://www.oecd

ilibrary.org/docserver/download/9721301e.pdf?expires=1408726996&id=id&accname=guest&checksum=29D935051 97D8AB40C63E8F0DFB4 47D0

14 USEPA. 2012. Ecological Effects Test Guidelines OCSPP 850.3020: Honey Bee Acute Contact Toxicity Test. Office of Chemical Safety and Pollution Prevention (7101). EPA

- 712

- C

- 019. January 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0016Page 23 of 35

Guideline Number: Non

- Guideline Study Title: Adult Honey Bee Chronic Oral Toxicity Rationale for Requiring the Data

This study is needed to evaluate the effects of repeat exposure to technical grade active ingredient (TGAI)

on honey bees

. Imazaquin is registered as a pre

- plant, pre

- emergence, and early post

- emergence broad spectrum herbicide for use soybeans, ornamentals, turfgrass, ornamental trees, shrubs, and groundcover where spray drift may settle on blooming non

- target plants and result in residues in pollen and nectar and represent a route of exposure to bees

.

Similar to other imidazolinone herbicides, i mazaquin is a likely systemic herbicide. It is absorbed by both roots and foliage and translocated via both xylem and phloem to pollen and/or nectar where it would represent a route of exposure to bees

. Residues 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.

The Agency finalized its framework to assess risk to pollinators 15 and these studies for all use sites where potential exposure to pollinators may occur. Although EPA has not developed a guideline for this study and OECD has yet to finalize test guidance for chronic studies, efforts are currently underway to develop standar dized guidelines for assessing effects from chronic (10

- day ) repeat exposures to adult bees in the laboratory. Since no guideline is available, a protocol should be submitted for EPA review and approval prior to study initiation. Practical Utility of the Data How will the data be used and how could the data impact the Agency’s future decision

- making?

The 10

- day chronic toxicity study with young adult bees provides data for assessing effects on bees from repeat exposure to technical grade active ingredient (TGAI). Data obtained from this study will be used in estimating chronic risk to individual (solitary bees) adult bees and well as potential risks to the honey bee colony (social 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 risk assessment written in support of Registration Review as well as for future endangered species assessments. The se data would allow the Agency to better characterize the potential for risk to insects (including beneficial pollinators) from the use of imidazolinone

- class chemicals. Th e s e data can be used by the Agency to determine whether any mitigations are needed. If the R egistration R eview 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, including bees and beneficia l pollinators, directly (and endangered species from other taxa indirectly), and uses of imazaquin might need to be restricted in areas where pollinators could be exposed.

10. REFERENCES

USEPA. 1994. Review of Studies for Unconditional Registration: 000241

- 00287 SCEPTER Herbicide Technical. Akiva Abramovitch. 04/18/94. DP Barcode: D197157.

U. S. Geological Survey (USGS). 2003. 1997 Pesticide Use Maps. NAWQA Pesticide National Synthesis P roject. September 3, 2003.

15 Ibid USEPA et al . 2014Page 24 of 35

http://water.usgs.gov/nawqa/pnsp/usage/maps/show_map.php?year=1997&map=IMAZAQUIN &hilo=H

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. United States Environmental Protection Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. Available at http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf (Accessed April 8, 2014)

USEPA. 2005a. Drinking Water Assessment for Imazaquin and its Salts. Keara Moore. 06/21/05. DP Barcode: D313182

USEPA. 2005b. Amendment to Drinking Water Assessment for Imazaquin and its Salts. Keara Moore. 09/27/05. DP Barcode: D313182

USEPA. 200 5c. Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision ( TRED) for Imazaquin. December 2005. EPA 738

- R

00

- 009.

USEPA. 2007a. Ecological Incident Information System. http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf

USEPA. 2007b. 40 CFR Part 158. Pesticides; Data Requirements for Conventional Chemicals: Final Rule. 72 FR 60934. October 26, 2007

USEPA. 2014a. Imidazolinone passerine bird study discussion. Office of Pesticide Programs, Potomac Yard South. Meeting held 3/13/14

USEPA. 2014b. Biological and Economic Analysis Division (BEAD) Chemical Profile for Registration Review: Imazaquin (128848) and Imazaquin, monoammonium salt (128840).

USEPA, PMRA and CDPR, 2014c. Guidance for Assessing Pesticide Risks to Bees. Office o f Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, Sacramento, CA. June 23, 2014.Page 25 of 35 

### A ppendices

Appendix A. BEAD Chemical Profile 1

1 Double

- click to open the filePage 26 of 35

Appendix B

. Submitted Environmental Fate and Ecological Effects Studies
Environmental Fate Studies Accession # Citation Reference 072014/131546 Herbicide AC 252,214: The Hydrolysis of carbon

- 14 Labeled AC 252,214. B. Reichert.

American Cyanamid Company. Report No. PD

- M. Volume 20

- 9. April 25, 1983. Acc. No. 072014. 073704/146209 Barringer, D. June, 1985. Scepter herbicide, imazaquin (AC 252,214): Photolysis in aqueous

solution. American Cyanamid Company, Princeton, NJ. Report No. PD

- M. Acc. No. 073704. Vol. 22, Sec. 15. 073704/146210 Barringer, D. and P. Stanley

- Millner. June 1985. Scepter herbicide, imazaquin ( AC 252,214):

Photolysis on soil thin

- layers. American Cyanamid Company, Princeton, NJ. Acc. No. 073704. Vol. 22, Sec. 16. 073704/146211 Mallipudi, M. September, 1983. Scepter herbicide (AC 252,214): aerobic soil metabolism of

carboxyl carbon

- 14 labeled AC 252,214 [3

- quinolinecarboxylic acid, 2

- (4

- i sopropyl

- 4

- methyl

- 5

- oxo

- 2

- imidazolin

- 2

- yl)

- ] in sandy loam soil, American Cyanamid Company, Princeton, NJ. Report No. PD

- M. Acc. No. 073704. Ref. Vol. 20, Sec. 23. 073704/146212 Mallipudi, M., B

. Knoll, and A. DaCunha. May, 1985. Scepter herbicide, imazaquin (AC

252,214): Anaerobic soil metabolism of carboxyl carbon

- 14 labeled AC 252,214 [3

- quinolinecarboxylic acid, 2

- (4

- isopropyl

- 4

- methyl

- 5

- oxo

- 2

- imidazolin

- 2

- yl)

- ] in sandy loam soil. American Cyanamid Company , Princeton, NJ. Report No. PD

- M. Acc. No. 073704. Ref. Vol. 22, Sec. 11Page 27 of 35

073704/146213 Fung, C. September, 1983. Scepter herbicide (AC 252,214): Adsorption and desorption

coefficients for soils. American Cyanamid Company, Princeton, NJ, Report No. PD

- M. Acc. No. 073704. Vol. 20, Sec. 24. 073704/146214 Mangles, G., and L. Lucas. June, 1985. Scepter herbicide, imazaquin (AC 252,214):

Adsorption/desorption on soil. American Cyanamid Company, Princeton, NJ. Report No. PD

- M. Acc. No. 073704. Vol. 22, Sec. 19. 073704/131564 Mallipudi, M., B. Knoll, and P. Stanley

- Millner. September, 1983. Scepter herbicide ( AC

252,214) : Field dissipation of carboxyl carbon

- 14 labeled AC 252,214 [3

- quinolinecarboxylic acid, 2

- (4

- isopropyl

- 4

- methyl

- 5

- oxo

- 2

- imidazolin

- 2

- yl

- )

- ]. American Cyanamid Company, Princeton, NJ. Report No. PO

- M. Acc. No. 073704. Vol. 20, Sec. 22. Ecological Effects Studies MRID Citation Reference

71

- 1 Avian Single Dose Oral Toxicity

131559 Fletcher, C. (1983) Report to ...: Acute Oral Toxicity Study with AC 252,214 Technical in

Mallard Ducks: BLAL No. 82 DD 16. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; prepared by Bio

- Life Assoc., Ltd., submitted by American Cyanamid Co., Pr inceton, NJ; CDL:072012

- G)

131558 Fletcher, D. (1983) Report to ...: Acute Oral Toxicity Study with AC 252,214 Technical in

Bobwhite Quail: BLAL No. 82 QD 17. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; prepared by Bio

- Life Assoc., Ltd., s ubmitted by American Cyanamid Co., Princeton, NJ; CDL:072012

- F) 71

- 2 Avian Dietary Toxicity

131560 Fletcher, D. (1983) 8

- Day Dietary LC50 Study with AC 252,214 Technical in Bobwhite

Quail: BLAL No. 82 QC 20. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; prepared by Bio

- Life Assoc., Ltd., submitted by American Cyanamid Co., Princeton, NJ; CD L:072012

- H)

131561 Fletcher, D. (1983) 8

- Day Dietary LC50 Study with AC 252,214 Technical in Mallard

Ducklings: BLAL No. 82 DC 20. (Unpublished study received Oct 14, 1983 under 241

- EX

108; prepared by Bio

- Life Assoc., Ltd., submitted by American Cyanami d Co., Princeton, NJ; CDL:072012

- I) 72

- 1 Acute Toxicity to Freshwater Fish

131554 Cohle, P.; McAllister, W. (1982) Acute Toxicity of AC 252,214 to Channel Catfish ( Ictalurus

punctatus ): Static Bioassay Report #29713. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; prepared by Analytical Bio

- Chemistry Laboratories, Inc., submitted by American Cyanamid Co., Princeton, NJ; CDL:072012

- B)

131555 Cohle, P.; McAllister, W. (1982 ) Acute Toxicity of AC 252,214 to Bluegill Sunfish ( Lepomis

macrochirus ): Static Bioassay Report #29711. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; prepared by Analytical Bio

- Chemistry Laboratories, Inc., submitted by American Cyanamid Co. , Princeton, NJ; CDL:072012

- C)

131556 Cohle, P.; McAllister, W. (1982) Acute Toxicity of AC 252,214 to Rainbow Trout

( Oncorhynchus mykiss formerly Salmo gairdneri ): Static Bioassay Report #29712. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; pre

- pared by Analytical Bio

Chemistry Laboratories, Inc., submitted by American Cyanamid Co., Princeton, NJ; CDL:072012

- D) 72

- 2 Acute Toxicity to Freshwater Invertebrates

131557 Forbis, A.; Kintner, D. (1982) Acute Toxicity of AC 252,214 to Dap hnia magna : Static

Acute Bioassay Report #29714. (Unpublished study received Oct 14, 1983 under 241

- EX

108; prepared by Analytical Bio

- Chemistry Laboratories, Inc., submitted by American Cyanamid Co., Princeton, NJ; CDL:072012

- E) 141

- 1 Honey bee Acute Toxicity

131562 Atkins, E. (1983) Letter sent to T. Wang dated Mar 14, 1983 Testing 252,214 against honey

bees|. (Unpublished study received Oct 14, 1983 under 241

- EX

- 108; prepared by Univ. of California

-- Riverside, Dept. of Entomology, submitted by American Cyanamid Co.

, Princeton, NJ; CDL:072012

- J) 123

- 1 Seed germination/seedling emergence and vegetative vigorPage 28 of 35

44996103 Canez, V.; Chetram, R.; Goodman, V. (1997) Tier 2 Nontarget Terrestrial Plant Vegetative

Vigor Phytotoxicity Study Using AC252214 (Imazaquin) in a 1.5 AS Formulation: Lab Project Number: 96572: ECO 96

- 110: 954

- 96

- 110. Unpublished study prepared by ABC Labs., California. 306 p. {OPPTS 850.4250}

45011801 Canez, V.; Chetram, R.; Goodman, V. (1997) Nontarget Terrestrial Plant Seedling

Emergence Ph ytotoxicity Study Using AC 252214 (Imazaquin) in a 1.5 AS Formulation: Lab Project Number: 96571: ECO

- 96

- 109. Unpublished study prepared by ABC Labs. 238 p. {OPPTS 850.4225}Page 29 of 35 Appendix C

. EIIS Incidents

Table C

- 1. Incidents in the EIIS for PC 128848: Imazaquin as of 4/8/14

Type Incident

ID Use Site Start Date Legality Certainty State County Total Magnitude Appl.

Rate Appl.

Method Air/Gnd Formulation Product

Plants I000360

-

014 Beans 1/1/1993 Registered Use Possible MO 160 ac beans N/R Soil

incorporation Seed

treatment Scepter

Plants I005880

-

054 Agricultural

Area 5/2/1997 Misuse (accidental) Probable WI 1.3 acres Spray Gnd Scepter

Plants I005880

-

057 Agricultural

Area 6/1/1997 Undetermined Probable MN Unknown Spray Gnd Scepter

Plants I005880

-

059 Agricultural

Area 6/1/1997 Undetermined Probable WI Unknown Spray Gnd Scepter Abbreviations: Appl.=Application; N/R=Not Recorded

1 Legality Code: RU=Registered Use, M=Misuse, MA=Misuse (Accidental), MI=Misuse (Intentional), U N =Unknown

2 Certainty Code: 0=Unrelated, 1=Unlikely, 2=Possible, 3=Probable, 4=Highly Probable. N/R=Not Reported

3 Formulation Code: DF=Dry Flowable; EC=Emulsifiable Concentrate; F= Flowable; G=Granular; WDG=Water Dispersable Granule; WP=Wettable Powder

Table C

- 2. Incidents in the EIIS for PC 128840: Ammonium Salt of Imazaquin as of 4/8/14

Type Incident

ID Use Site Start Date Legality Certainty State County Total Magnitude Appl.

Rate Appl. Method Air/Gnd Formulation Product

Plants I016225

- 001 N/R 4/5/2005 Undetermined Possible IL Fayette 1 acre N/R Spray Roundup + Plateau Abbreviations: Appl.=Application; N/R=Not Recorded

1 Legality Code: RU=Registered Use, M=Misuse, MA=Misuse (Accidental), MI=Misuse (Intentional), U N =Unknown

2 Certainty Code: 0=Unrelated, 1=Unlikely, 2=Possible, 3=Probable, 4=Highly Probable. N/R=Not Reported

3 Formulation Code: DF=Dry Flowable; EC=Emulsifiable Concentrate; F= Flowable; G=Granular; WDG=Water Dispersable Granule; WP=Wettable PowderPage 30 of 35 Append ix D

. Aggregate Incident Reports for Imazaquin and the Ammonium Salt of Imazaquin

Table D

- 1

. Aggregate Incident Reports for ImazaquinPage 31 of 35 Table D

- 2

. Aggregate Incident Reports for the Ammonium Salt of ImazaquinPage 32 of 35

Appendix E

. SIP Results for Evaluate Potential Risk to Birds and Mammals from Drinking Water ExposurePage 33 of 35

Appendix F

. STIR Results to Evaluate the Potenti al for Inhalation Risk to Birds and MammalsPage 34 of 35

Appendix G. Chemical structures of imazaquin and identified major photo degradates

Imazaquin

3

- quinolinecarboxylic acid

2,3 qu inolinedicarboxylic acid imide

2,3

- dihydro

- 3

- imino

- 1H

- py rrolo

- [3,4b]quinolin

- 1

- onePage 35 of 35 2,3 quinolinedicarboxylic acid