### UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY WASHINGTON D.C., 20460

July 10, 2009

PC Code: 

### 128724

DP Barcode: 

### 362087

MEMORANDUM

Subject: Registration Review – Preliminary Problem Formulation for the Ecological Risk Assessment of Flumiclorac-pentyl

To: Monica Wait, Chemical Review Manager

Review Branch 3 Special Review and Reregistration Division

Michael Goodis, Branch Chief

Review Branch 3 Special Review and Reregistration Division

From: Wm. J. Shaughnessy, Ph.D., Environmental Scientist Amy Blankinship, Chemist

Environmental Risk Branch 2

Environmental Fate and Effects Division Office of Pesticide Programs

Through: Jean Holmes, Risk Assessment Process Leader

Environmental Risk Branch 2

Environmental Fate and Effects Division Office of Pesticide Programs

Tom Bailey, Ph.D., Branch Chief

Environmental Risk Branch 2

Environmental Fate and Effects Division Office of Pesticide Programs



### The Environmental Fate and Effects Division (E FED) has completed the preliminary problem formulation (attached) for the ecological ris k, environmental fate, and endangered species assessment to be conducted as part of the Regi stration Review of the herbicide, flumicloracpentyl (PC Code 128724). Functioning as the firs t stage of the risk assessment process for registration review, this problem formulation provides an overvi ew of what is currently known

about the environmental fate and ecological effects associated w ith flumiclorac-pentyl and its degradates. It also describes the preliminary ecological risk hypothesis and analysis plan for

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### 2 of 67 evaluating and characterizing ri sk to non-target species in support of the re gistration of flumiclorac-pentyl.

Attachment: Problem Formulation for the Enviro nmental Fate, Ecological Risk, and Endangered Species Assessments in Support of the Registration Review of Flumiclorac-pentyl.

# Problem Formulation for the Environmental Fate, Ecological Risk, and Endangered Species Assessmentsin Support of the Registration Review of Flumicloracpentyl

Flumiclorac-pent yl (CAS 87546-18-7)

Prepared by: Amy Blankinship, Chemist 

### Wm. J. Shaughnessy, Ph.D., Environmental Scientist

Reviewed by: Jean Holmes, Senior Biologist William Eckel, Senior Fate Scientist Tom Bailey, Branch Chief U. S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division

Environmental Risk Branch II 1200 Pennsylvania Ave., NW

Mail Code 7507P Washington, DC 20460



### June 23, 2009

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### Table of Contents

1.Purpose......................................................................................................................................... 4

2. Problem Formulation ......................................................................................................... ..... 4 2.1. Nature of Regulatory Action........................................................................................... 4

2.2. Previous Risk Assessments............................................................................................. 4

3. Stressor Source and Distribution ............................................................................................ 5

3.1. Mechanism of Action...................................................................................................... 5 3.2. Overview of Pesticide Usage.......................................................................................... 5 3.3. Environmental Fate and Transport.................................................................................. 7 4. Receptors................................................................................................................... ............ 13 4.1. Effects to Aquatic Organisms ....................................................................................... 14 4.2. Effects to Terrestrial Organisms ................................................................................... 17

4.3. Incident Database Review............................................................................................. 19 4.4. Ecosystems Potentially at Risk ..................................................................................... 19 5. Assessment Endpoints ........................................................................................................ .. 19 6. Conceptual Model............................................................................................................ ..... 19 6.1. Risk Hypothesis ........................................................................................................... . 20 7. Analysis Plan ............................................................................................................... ......... 22

7.1. Stressors of Concern ..................................................................................................... 22 7.2. Measures of Exposure................................................................................................... 23

7.3. Measures of Effect ........................................................................................................ 24 7.4. Integration of Exposure and Effects ............................................................................. 25

7.5. Deterministic and Probabilistic Assessment Methods.................................................. 25 7.6. Endangered Species Assessments................................................................................. 25 7.7. Preliminary Identification of Data Gaps....................................................................... 26

7.7.1 Fate..................................................................................................................... ... 26

7.7.2 Effects .................................................................................................................. . 26

8. Data Call In Tables ......................................................................................................... ...... 34

9. References.................................................................................................................. ........... 40 9.1. Open Literature ........................................................................................................... .. 40

9.2. Submitted Fate Studies ................................................................................................. 42

9.3. Submitted Effects Studies............................................................................................. 45

List of Tables

Table 1 - Cropland Use Pattern s for Flumiclorac-pentyl................................................................ 6

Table 2 Screening Level Estimates of Agricultural Uses of Flumiclorac-pentyl ................... 6

Table 3 Summary of national labels, formulations, and maximum application rates for products containing flumiclorac-pentyl*................................................................................................. ...... 7

Table 4 Summary of Fate Prope rties of Flumiclorac-pentyl ....................................................... 12

Table 5 Summary of sensitive endpoints for aqua tic organisms under consideration for use in the risk assessment for flumiclorac-pentyl* ....................................................................................... 1 6

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### Table 6 Summary of sensitive toxicity endpoints for terrestrial organisms under consideration

for use in risk assessment*.................................................................................................... ........ 18

Table 7 Available Ecological Effects Data fo r Terrestrial Plants and Animals Exposed to Flumiclorac-pentyl and Remaining Data Gaps............................................................................. 27

Table 8 Available Ecological Effects Data for Aquatic Animals Exposed to Flumiclorac-pentyl and Remaining Data Gaps ............................................................................................................ 28

List of Figures

Figure 1 Chemical Structure of Parent and Degradates.................................................................. 8

Figure 2 Ecological Conceptual Model for Flumiclorac-pentyl.................................................. 21

Appendices

Appendix A: Summary of Toxicity Data..................................................................................... 54

Appendix B. Memorandum: Request for Photot oxicity Study Protocol for Light-Dependent Peroxidizing Herbicides................................................................................................................ 62

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### 1. Purpose

The purpose of this problem formulation is to pr ovide an understanding of what is known about the environmental fate and ecological effects of the registered uses of flumiclorac-pentyl. Flumiclorac-pentyl is a N-phenylphthalimide derivati ve herbicide. This document will provide a plan for analyzing data relevant to flumiclo rac-pentyl and for conduc ting environmental fate, ecological risk, and endangered species assessment s for its registered uses. Additionally, this problem formulation is intended to identify data gaps, uncertainties, a nd potential assumptions

used to address those uncertainties relative to characterizing the ecological risk associated with the registered uses of flumiclorac-pentyl.

2. Problem Formulation

2.1. Nature of Regulatory Action

Under the Federal Insecticide, F ungicide, and Rodenticide Act (FIF RA), all pesticid es distributed or sold in the United States ge nerally must be registered by the United States Environmental Protection Agency (U.S. EPA). To determine wh ether a pesticide can be registered, the U.S. EPA evaluates its safety to non-ta rget species based on a wide range of environmental and health effects studies. In 1996, FIFRA was amended by the Food Quality Protection Act, and EPA was mandated to implement a new program for the periodic review of pesticides, i.e ., registration

review 1 

### . The registration review program is intended to ensure that, as the ability to assess risk evolves and as policies and practi ces change, all registered pes ticides continue to meet the statutory standard of no unreasonable adverse e ffects to human health and the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the new registration review program, the Agency peri odically reevaluates pesticides to make sure that as change occurs, products in th e marketplace can be used safely.

As part of the implementation of the new Regist ration Review program purs uant to Section 3(g) of FIFRA, the Agency is beginni ng its evaluation of fl umiclorac-pentyl to determine whether it

continues to meet the FIFRA standard for re gistration. This problem formulation for the environmental fate and ecological risk assessmen t chapter in support of the registration review will be posted in the initial docket opening the public phase of the review process.

2.2. Previous Risk Assessments

The risk assessments available in the docket which serve as the basis for this problem formulation include the following:

• October 31, 2005 Environmental Fate and Effect s Science Chapter, Environmental Fate and Ecological Risk Assessment, Registra tion for New Use for Flumiclorac-pentyl

• October 19, 2005 Flumiclorac-pentyl; Tolerance R eassessment Decision for Low Risk Pesticide; Notice of Availability, EPA-HQ-OPP-2005-0229-0001

.

1 http://www.epa.gov/oppsrrd1/registration_review/



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### • September 15, 2005 Report of the Food Quality Protection Act (FQPA) Tolerance Assessment Progress and Risk Management Decision (TRED), EPA-HQ-OPP-2005-

0229-0002

• September 15, 2005 HED Chapter of the TRED, EPA-HQ-OPP-2005-0229-0003

• September 15, 2005 Flumiclorac-pentyl Chronic Di etary Assessment for the TRED, EPA-HQ-OPP-2005-0229-0004

• September 15, 2005 Flumiclorac-pentyl. Residue Chem for the TRED

, EPA-HQ-OPP2005-0229-0005

• September 15, 2005 Flumiclorac-pentyl TRED Product Chem Considerations, EPA-HQOPP-2005-0229-0006

• September 15, 2005 Flumiclorac-pentyl Tier 1 Drinking Water Assessment, EPA-HQOPP-2005-0229-0007

• September 15, 2005 Flumiclorac-pentyl EFED Addendum No.1 to MRID#42169844, EPA-HQ-OPP-2005-0229-0008

• September 15, 2005 Flumiclorac-pentyl EFED Addendum No.1 to MRID#43304601, EPA-HQ-OPP-2005-0229-0009

• March 14, 1994 EEB Hazard Assessment Science Chapter V-23031, DP165814, 195820

and 199998

The conclusion of the Risk Assessment for the New Use of Flumiclorac-pentyl (US EPA, 2005a)

was that adverse risk to listed and non-lis ted terrestrial dicot plants is expected.

3. Stressor Source and Distribution

3.1. Mechanism of Action

Flumiclorac-pentyl [(2-chloro-4-fluoro- 5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2- yl)phenoxy) acetic acid, pentyl es ter] is a N-phenylphthalimide de rivative herbicide used for the

control of broadleaf weeds. Its mode of action is through the accumulation of porphyrins in susceptible plants. In turn; the photosensiti zing action of accumulated porphyrins may cause membrane lipid peroxidation which leads to ir reversible damage of membrane function and structure in the target plant.

3.2. Overview of Pesticide Usage

Flumiclorac-pentyl is registered for post-emergence application to field corn and soybeans, and

as a defoliant on cotton. Table 1 contains the cropland use patterns and estimated annual quantities for flumiclorac-pentyl. The herbicide is also used on non-crop ar eas such as industrial sites, airports, military installations, roadsides, ri ghts of way, and other similar areas to control a selected group of broadleaf weed s, specifically morning glory and velvet leaf. According to the Health Effects Division (HED) Label Datareport (US EPA 2008), the maximum nonagricultural use rate is 0.028 lb ai/A, however, the Biol ogical Economics Analysis Division (BEAD) was unable to find Screening Level Usag e Analysis (SLUA) data for non-agricultural

national use estimates.

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### Table 1 - Cropland Use Patterns for Flumiclorac-pentyl

Crop 1 Max Single Rate (lbs ai/A) Applications/

Yr Maximum Seasonal Rate (lbs ai/A/Yr) RTI
(days) 2 SLUA Estimates (lbs. a.i.)

Corn, field 0.054 2 0.054 14 1,000 Soybean 0.081 2 0.11 14 10,000

Cotton 0.054 2 0.094 14 1,000

1 From Flumiclorac-pentyl Use Closure Memo, T. Spears, 29-SEP-2004; and Resource label

2 Retreatment Interval



### Table 2 provides estimates of the national-level usag e of flumiclorac-pentyl. According to the table provided by the Biological Economics Analys is Division in OPP (BEAD), the major uses were on corn, cotton, and soybeans.

The uses marked with the “+” sy mbol represent crops that were not known to be listed on active end use product registrations when this report was run. The lbs A.I. values listed in the table are average application amounts that span over a 7 year period (2001 to 2007). As a result, cancelled uses may appear in the table. The regi stered formulations include soluble concentrate, dust, wettable powder, granular, liquid, and pe lleted or tableted (BEAD, August, 2008).

Table 2 Screening Level Estimates of Agri cultural Uses of Flumiclorac-pentyl Sorted Alphabetically

Crop Lbs. A.I. Percent Crop Treated Avg. Max.

1 Corn 1,000 <1 <2.5

2 Cotton 1,000 <1 <2.5

3 Potatoes + <500 <1 <2.5

4 Rice + <500 <1 <2.5 5 Soybeans 10,000 <1 <2.5

All numbers rounded. '<2.5' indicates less than 2.5 percen t of crop is treated.
'<1' indicates less than 1 percent of crop is treated



### .

SLUA data sources include: USDA-NASS (United States Department of Agriculture's National Agricultural Statistics Service); 2001-2007

Private Pesticide Market Research, 2001-2007 NPUD 2002 (National Pesticide Use Database) of the CropLife America Foundation and California DPR data. These results reflect amalgamated data developed by the Agency and are releasable to the public. + = These crops were not known to be listed on active end use product registrations when this report was run.



### The herbicide was first registered in 1994. There are a total of fi ve FIFRA Section 3 labels. All active products are registered by Valent USA Cor p. In addition, there is one Experimental Use Permit (EUP) and a Special Local Need (SLN) was issued to the State of Missouri. The

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### tabulated FIFRA Section 3 registrations for flum iclorac-pentyl were found in OPPIN and can be

found in Table 3

.

The herbicide can be applied as a liquid, emulsifi able concentrate, and as a wettable powder. Flumiclorac-pentyl is applied via aircraft, gr oundspray, back pack sprayer, ground boom, hand held, and band sprayer at various application rates depending on the application method, crop, and applicable label. The produc ts containing flumiclorac-pentyl have a wide assortment of active ingredient concentrations ra nging from 0.576% ai to 80.0% ai.

Table 3 Summary of national labels, formulations, and maximum application rates for products containing flumiclorac-pentyl*

Product Name EPA Reg. Num.

Percent ai Formulation

Pounds ai/amount product Maximum Application Rate (Active Ingredient)

Resource Herbicide

59639-82

10.1% ai Emulsifiable Concentrate 0.86 lb ai/gal product 0.054 lb ai/Acre (Corn), 0.11 lb ai/Acre (Soybeans) and 0.094 lb ai/Acre (Cotton) 1

Stellar Herbicide

59639-92

7.6% ai Emulsifiable Concentrate 0.7 lb ai/gal product 0.038 for a single application to 0.055 lb ai/Acre for single growing season (Soybeans) 2

Resource 80 WP

59639-100

80% ai Wettable Powder 0.081 lb ai/Acre for a si ngle application and 0.11 lb ai/Acre for a single growing season for soybeans, and one maximum application of 0.054 lb ai/Acre for corn

V-10097 Herbicide

59639-122

0.576% ai Emulsifiable Concentrate 0.056 lb ai/gal product 0.028 lb ai/Acre (Corn), 0.042 lb ai/Acre (Soybeans) 3 , and 0.028 lb ai/Acre for non agricultural uses,

Flumiclorac-pentyl

Technical

59639-81

98.6% ai Not applicable

*The list of currently registered products was obtained from OPPIN in April 2009. 1 Calculated from 8, 16 or 14 fl oz pr oduct/acre x 1gallon/128 oz conversion factor x 0.86 lbs ai/gallon = 0.054, 0.11 and 0.09 4

lbs ai./Acre. 2 Calculated from 7 or 10 fl oz product/acre x 1gallon/128 oz co nversion factor x 0.7 lbs ai/gallon = 0.038 or 0.055 lbs ai./Ac re. 3 Calculated from 64 or 96 fl oz product/acre x 1gallon/128 oz conversion factor x 0.056 lb s ai/gallon = 0.028 or 0.042 lbs ai./Acre. Non agricultura l maximum rate from BEAD.



### 3.3. Environmental Fate and Transport

Laboratory and field data s uggest that parent flumiclo rac-pentyl is not persis tent or mobile in soil and aqueous environments. While aerobic aquati c metabolism data are not available, aqueous photolysis (4 days) and hydrolysis (19 hours at pH 7) half-life data suggest that the parent metabolizes rapidly into degradates.

The primary degradate of flumiclorac-pentyl found in aerobic soil metabolism studies is 2- chloro-4-fluoro-5-(3,4,5, 6-tetrahydrophthalimido) phenoxyacetic acid (IMCA). This compound is structurally similar to the parent compound and is , therefore, expected to have similar toxicity.

IMCA concentration was a maximum of 53% of the applied at 1 day post-treatment, and decreased to 20.6% at 7 days and 1.8% at 85 days.

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### Flumiclorac-pentyl also degrad es into a number of bulky anioni c degradates which are mobile and may be bioactive. However, these degradates also do not appear to be especially persistent,

with soil half-lives of two weeks.

Under abiotic hydrolysis at pH 5 and 7, the tetrahydrophthalimido group breaks off to form tetrahydrophthalic acid (THPA). At pH 5, the phenyl substituted ring moiety appears to be more stable, with pentyl 5-amino-2-chloro–4-fluoroph enoxyacetate (AFE) the fina l product. At pH 7, this moiety degrades further to 5-amino-2-ch loro-4-fluorophenoxyacetic acid (AFCA). At pH 9, degradation does not appear to be as complete, with 2-chloro-4-fluoro-5-(3,4,5,6- tetrahydrophthalimido) phenoxyacetic acid (IM CA), and N-(5-carboxymethoxy-4-chloro-2- fluorophenyl)-3,4,5,6-tetrahydrophthalamic acid (IM CA-HA) the final products. Aerobic metabolism appears to degrade flumiclorac-pentyl first to IMCA, and then to AFCA and THPA. Within 85 days, both AFCA and THPA may be me tabolized further and become bound residues.

In the presence of light, furt her breakdown and/or mineraliza tion of flumiclorac-pentyl degradates occurs, although the hal f-life of parent flumiclorac-pent yl appears to be unaffected. While less than 0.5% of the applie d radioactivity is released as 14 

### CO 2 

### from flumiclorac systems maintained in the dark, the irradiated aqueous system with phenyl-labeled flumiclorac-pentyl

released 22.81% of the a pplied radioactivity as 14 

### CO 2 

### . This effect is less striking on soil: 7.32% of the applied radioactivity was mineralized to 14 

### CO 2 

### when phenyl-labeled flumiclorac-pentyl was applied to viable soil and irradiated for 21 days. Figure 1 presents the chemical structure of the parent and degradates.

Figure 1 Chemical Structure of Parent and Degradates
Company Name Chemical Name Structure

Flumicloracpentyl



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### According to the Drinking Water Assessment (D WA) for flumicolorac-pe ntyl (EPA 2005), the assumption was that the residues of interest ar e parent flumiclorac-pe ntyl (CAS Reg No. 87546- 18-7), and the major degradate in the aerobic soil metabolism studies (IMCA or flumicloracacid, CAS Reg. No. 87547-04-4). The aerobic soil metabolism studies (MRID 42169844 and 43304301) indicate that the parent flumiclorac-pentyl and the degradate IMCA half-life is 7 to 8 days. An aerobic aquatic metabolism study with parent flumiclorac-pentyl or data on the aquatic persistence with the degradate IMCA was not ava ilable, therefore, the persistence of IMCA in the aquatic environment is not known. EFED will compare the proposed use rates for corn and soybeans with those described in the 2005 DWA to determine whether a new DWA is required.

Field data confirm that flumiclorac-pentyl and its degradates do not leach. Although flumiclorac-pentyl degrades to compounds that do not bind strongly to soil, these compounds themselves appear to be so short-lived in the soil that they degrade further before moving a significant distance through the soil. However, the fate of flumiclorac-pe ntyl residues at the

surface is less clear. In radiolabeled lysimeter studies, near ly 50% of the applied radioactivity appears to have dissipated to the atmosphere in the course of studies ranging from 112 to 120 days, with the fastest dissipation occurring in 14 days. This far exceeds the rate of mineralization reported in the laboratory, and raises the possibility that some of the parent material or degradates may be volatilizing. This possible volatiliza tion is based only on one study and it can not be determined if volatilizatio n is occurring, and if so, what degradates or percent parent is contributing to this possible vo latilization. Therefore, volatilization will not be considered at this point.

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### In an unconfined field situation, some of the flumiclorac-pentyl degradates could be entrained in runoff. Although the anaerobic aquatic metabo lism study suggests that the majority of the

material is associated with the soil rather than the water, there are periods when the majority of the material may associate with the water. In the field study in Kent ucky, up to 28.65% of the applied radioactivity was found in the surface water at day 3. Many early flumiclorac-pentyl degradates include large portions of the origin al molecule, and their off-site movement may represent a hazard to non-target organisms. Howe ver, the flumiclorac-pentyl degradates N-(4- chloro-2-fluoro-5-pe ntoxycarbonylmethoxypheny1-3,4,5,6

- tetrahydrophthalamic acid (031 - HA); and pentyl 5-amino-2-chloro-4-fl uorophenoxy acetate (AFE) appear to be more susceptible to photolysis when they are in solution, and woul d be unlikely to persist for more than a few days in an aquatic environment. A summar y of the environmental fate properties from laboratory and field studies is found in Table 4

.

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### Table 4 Summary of Fate Properties of Flumiclorac-pentyl

Property Value (Source Reference)

Physical state at room temperature beige powdered solid, mp 88.9-

90.1 ° C Pesticide Properties database (PPDB)

05/26/2009

Molecular weight 423.86 Pesticide Properties

database 05/26/2009

Vapor Pressure at 25 ° C (mPa) 0.01 Pesticide Properties

database 05/26/2009

Henry’s Law Constant at 20 ° C (atm-m 3 /mol) < 3 E-7 calculated from VP and solubility

Water solubility at 20 ° C (milligrams per liter; mg/l) 0.189 Pesticide Properties

database 05/26/2009

Hydrolysis 87.4 hrs at pH5 18.8 hrs at pH7 5.9 mins at pH9 MRID 42169842

Pesticide Properties

database 05/26/2009

Direct Aqueous Photolysis (half-life, days) 4 days MRID 42825824

Soil Photolysis (half life, days) 21.5 - 37.0 hrs at 25°C MRID 428258826,

42825827

Aerobic Soil Metabolism (half-life, days) 7.3 - 8.04 days (parent and (IMCA) MRID 42169844,

43304601 as amended

Anaerobic Soil Metabolism (half-life, days) 0.11 MRID 42825829

Anaerobic Aquatic Metabolism (half-life, days) 2.5 - 2.7 hr (parent) MRID 42825829,

42825830

Aerobic Aquatic Metabolism (half-life, days) No data

K

oc (milliliters/gram) 30 Pesticide Properties

database 05/26/2009

Log octanol-water partition coefficient (log K

ow ) 4.99 Pesticide Properties

database 05/26/2009

Soil Dissipation (half-life, days) < 5 (four sites) MRID 42825836

Aquatic Dissipation (half-life, days) No data

Fish Accumulation (BCF); concentration in tissue to exposure concentration in water 21X edible tissue

837X non-edible

372X whole fish MRID 421698-09,10

MRID 428268-12,13

Pesticide Fact Sheet: Flumiclorac-pentyl,

11/18/1994



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### Based on acceptable and supplemental data, flumic lorac-pentyl is not persistent under aerobic conditions, and is not expected to be persistent in anaerobic aquatic environments where it will be associated with the aqueous phase due to its s hort anaerobic half-life. The degradate IMCA is expected to be mobile and be present in the aquatic environments off- field. Aerobic aquatic metabolism with parent flumiclorac-pentyl or da ta on the aquatic persiste nce with the degradate IMCA was not available, therefor e, the persistence of IMCA in the aquatic environment is not

known.

Clean Water Act Flumiclorac-pentyl is not identified as a cause of impairment for a ny water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail_303d?p_cause_group_id=88

5 . In addition, no Total Maximum Daily Loads (T MDL) have been developed for flumicloracpentyl, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation.tmdl_pollutant_de tail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES . More information on impaired water bodies and

TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The Agency invites submission of water quality data for this pesticide. To the exte nt possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process (see: http://www.epa.gov/oppfead1/cb/ ppdc/2006/november06/session1- sop.pdf ), in order to ensure they can be used qua ntitatively or qualitatively in pesticide risk

assessments.

4. Receptors

The receptor is the biological entity that is e xposed to the stressor (U.S . EPA 1998). Consistent with the process described in the Overview Do cument (U.S. EPA 2004), the risk assessment for flumiclorac-pentyl relies on a surrogate species approach. Toxicological data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, are used to extrapolate to potential effects on a vari ety of species (receptor s) included under these taxonomic groupings.

Acute toxicity data from studies submitted by pe sticide registrants along with the available open literature are used to evaluate the potential direct and indirect effects of flumiclorac-pentyl to aquatic and terrestrial receptors. There is no chronic toxicity da ta submitted by the registrant. Additional studies include toxicity on the techni cal grade active ingredient, degradates, and when available, formulated products ( e.g. , “Six-Pack” studies). The open literature studies are identified through EPA’s ECOTOXicology (E COTOX) database (U.S. EPA 2009), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evalua tion of both sources of data may also provide insight into the direct and indirect effects of flumiclorac-pentyl on biotic communities from loss of species that are sensitive to the chemical and from changes in structure and functiona l characteristics of the affected communities. Open literature data fr om ECOTOX on flumiclorac-pentyl was completed and resulted in no acceptable studies for inclus ion in the risk assessment at this time.

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### A summary of the aquatic and terrest rial toxicity data used to de rive a preliminary evaluation of risk for flumiclorac-pentyl is provided in Sections 4.1 and 4.2, respectively. In addition, a summary of ecological incidents associated w ith flumiclorac-pentyl and a description of ecosystems potentially at risk are prov ided in Sections 4.3 and 4.4, respectively.

4.1. Effects to Aquatic Organisms

A summary of sensitive aquatic toxicity data fr om registrant-submitted studies is provided in

Table 5

. Appendix A includes a table summarizing toxicity data submitted to the Agency.

The reported solubility of flumiclorac-pent yl is 0.189 mg/L (MRID 42187405). In discussions with Ecological Effects Branch (EEB) sta ff on January 18, 1989 and on February 27, 1992, the registrant indicated that preliminary aquatic animal testing with flumiclor ac-pentyl indicated they had problems achieving solubility wi thin the parameters outlined in guideline testing. They were unable to achieve solubility gr eater than 0.1 mg flumiclorac- pentyl/L with the guideline

recommended co-solvents at a concentration of 0.1 mL solvent/L test solution. They also indicated that no fish mortality was observed at 0.1 mg/L of flumiclora c-pentyl. Therefore,

alternative co-solvents and solvent concentratio ns for use in aquatic animal testing were requested by the registrant. EEB staff indicated that the registrant shoul d provide justification

for these extra measures and would view favor ably a well designed study which resulted in a dose response. The registrant provided info rmation for the use of dimethyl formamide: polyoxyethylene hydrogenated castor oil (1:1, DM F:HCO-40), and toxicity data for bluegill

sunfish and rainbow trout from this so lvent mixture (MRID 42169808). Based on this information, the aquatic studies were conducte d using a DMF:HCO-40 solvent concentration range of 0.56 mL/L – 4 mL/L for the fish studies, and 4 mL/L for the Daphnia magna toxicity study. The 96-hour acute mysid and oyster toxi city studies were conducted at solvent concentrations of 0.5 mL DMF/L only, as HCO- 40 was found to be toxic to oysters.

Even with the use of this alternative co-solve nt mixture and increased solvent concentrations, precipitate was observed in some of the aquatic toxicity studies. Precipitate was observed either

in the test chambers or the de livery system. No precipitate was reported in the 96-hour acute mysid toxicity study. Test solution appearance was not reported for e ither the acute rainbow trout or bluegill toxicity study. So while a pres ence of precipitate was not mentioned in these reports, the absence of precipitate can not be assumed based on the known solubility of the chemical and presence of precipitate in the othe r toxicity studies. Fo r all studies in which precipitate was observed, an attempt to remove th e precipitate from the an alytical samples prior to analysis (ex. centrifugation, filt ering) was not reported. Theref ore, it is not known what the actual dissolved flumiclorac-pentyl concentration in the test sy stems were, as the presence of precipitate during analysis could overestimate the actual exposure concentration. All of these studies were conducted above the reported solub ility of 0.189 mg/L for flumiclorac-pentyl, and therefore, the NOAEC level for al l aquatic studies are above this reported water solubility. LC 50 

### values were obtained for the blue gill sunfish, rainbow trout and my sid invertebrate, but with the exception of the mysid toxicity data, actual aqua tic exposure concentrations are uncertain. A LC, EC 50 

### concentration could not be determ ined for the sheepshead minnow or Daphnia magna toxicity study, respectively, due to a lack of dose response. Since th is uncertainty exists for these aquatic studies in which precipita te was observed these studies are classified as supplemental. Also, the 96-hour oyster shell gr owth deposition study was classifi ed as supplemental since there

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### was minimal new shell growth in the control treatment groups, substantial decrease in measured test solution concentration and dissolved oxygen fell below the required 60% of saturation for the four highest treatment groups. Since the dissolved oxygen was greater than 60% for the lowest treatment group (0.61 mg ai/L, mean measur ed), and the growth was comparable to the controls, it appears that flumiclorac-pentyl does not inhibit oyster shell growth at the reported limit of solubility (0.189 mg/L). Also, since th ere is an acceptable mysid toxicity study, that study will be used to evaluate estuarine-marine invertebrate risk to flumiclorac-pentyl. Therefore, the oyster deposition study will not need to be repeated at this time.

Based on the limited mobility of flumiclorac-pe ntyl and its degradation to IMCA, aquatic

vascular and non-vascular studies were conducted with IMCA at one concentration. This was done on the recommendation of EEB, and is based on information that IMCA is mobile in soil and expected to runoff, and its similar chemical st ructure to parent flumiclo rac-pentyl indicates it may be phytotoxic. The concentration of IMCA tested was based on the maximum application of flumiclorac-pentyl and the degradate IMCA co mprising 53% of the parent flumiclorac-pentyl (up to 1 day post-treatment), ther efore, the maximum application ra te of IMCA was determined. When this amount is applied into 6 inches of water, a concentration of IMCA in water was

determined and used as the limit concen tration. The aquatic vascular plant, Lemna gibba, toxicity study using IMCA at one concentrati on showed a 3.3 and 12% in crease in frond number and dry weight when compared to the negative control. The nonvascular, green algae toxicity study at the IMCA limit concentrat ion showed a 4.1% decrease in cell density compared to the negative control.

There is no chronic toxicity data fo r freshwater fish or invertebrate s, or estuarine-marine fish or

invertebrates.

In addition, flumiclorac-pentyl is a light-depen dent peroxidizing herbic ide (LDPH), and may be very toxic to living organisms. Therefore, The Aquatic Biology Tech Team (ABTT) recommends that phototoxicity st udies be conducted on herbicides with this mode of action to determine if animals exposed to LDPHs and inte nse light (similar to sunlight) show increased toxicity relative to controls exposed to LDPHs and low intensity light with the suggested test species, the fathead minnow (See Appendix C Memorandum: Request for Phototoxicity Study Protocol for Light-Dependent Pe roxidizing Herbicides, Dated Ma rch 7, 2001). A data call-in (DCI) was issued on January 25, 2006 for a fish early life-cycle study using enhanced lighting (GDCI-128724-26284). Based on flumic lorac-pentyl’s mode of action, adverse effects to aquatic organisms under natural s unlight are expected. Effects to estuarine-marine fish and aquatic-phase amphibians is also expected base d on expected effects to fish which are the surrogate species for amphibians.

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### Table 5 Summary of sensitive endpoints for aquatic organisms under consideration for use in the risk assessment for flumiclorac-pentyl*

Common Name (Species)

TGAI Duration End-point (effect) Mean

concentration in mg a.i./L (effect) Citation or

MRID/status or

review Acute Toxicity

Classification

Freshwater Vertebrates

Rainbow Trout ( Onchorhyncus mykiss )

TGAI 96 hours LC 50 > 0.189 1

1.1 2
(mortality) 42169806 Supplemental Moderately Toxic 3

Fathead Minnow (Pimephales promelas)

TGAI Full Lifecycle NOAEC No Data No Data No Data

Fathead Minnow (Pimephales promelas)

TGAI Early Life Stage under

enhanced UV lighting NOAEC No Data No Data No Data

Estuarine Marine Vertebrates

Sheepshead Minnow (Cyprinodon variegates)

TGAI 96 hours LC 50 > 0.189 1

> 24 2
(mortality) 42825809 Supplemental NA 4

Sheepshead Minnow (Cyprinodon variegates)

TGAI Early Life Stage under

enhanced UV lighting NOAEC No Data No Data No Data

Freshwater Invertebrates

Waterflea (Daphnia magna)

TGAI 48 hours EC50 > 0.189 1

> 38 2
(mortality) 42169808 Supplemental NA 4

Waterflea (Daphnia magna)

TGAI Full Lifecycle NOAEC No Data No Data No Data

Estuarine Marine Invertebrates

Mysid Shrimp (Americamysis bahia)

TGAI 96 hours LC 50 0.56 (morality) 42825801 Acceptable Highly Toxic

Mysid Shrimp (Americamysis bahia)

TGAI Full Lifecycle NOAEC No Data No Data No Data

Aquatic Nonvascular and Vascular Plants

Green Algae Selenastrum capricornutum 96 hours EC50 > 0.035 (IMCA) 43240800 Acceptable NA 4

Green Algae Selenastrum capricornutum 96 hours NOAEC 0.035 (IMCA) 43240800 Acceptable NA 4

Duckweed –Lemna gibba 14 day EC50 > 0.035 (IMCA) 43251201 Acceptable NA 4

Duckweed - Lemna gibba 14 day NOAEC 0.035 (IMCA) 43251201 Acceptable NA 4

TGAI=technical grade active ingredient; LC 50 = median lethal concentration; NOAEL=no observabl e adverse effect level; a.i. active ingredient * Data in this table may be used in the risk assessment, but it will not necessarily be used to calculate risk quotients.

1 No toxicity up to the reported limit of solubility (0.189 mg a i/L). Actual test concentrati on not known due to the presence o f precipitates in test solution or exclusion of test solution appearance and removal of possible precipitate from test solutions prior to analysis not reported.

2 Measured concentration reported in study.

3 Classification class based on reported meas ured test concentration and not greater than value based on reported solubility.

4 Due to no toxicity at both reported limit of solubility (0.189 mg ai/L), and measured test concentration, or limit test (aqua tic nonvascular and vascular plants with IMCA) toxicity classification could not be determined.



### 16 of 67

### 4.2. Effects to Terrestrial Organisms

A summary of sensitive terrestrial toxicity data from registrant-submitted studies is provided in

Table 6

. Appendix A includes a table summarizing toxicity data submitted to the Agency. Flumiclorac-pentyl is classified as practica lly nontoxic to birds, mammals, and terrestrial

invertebrates.

Acute, subchronic, and chronic t oxicity studies are available for mammals. According to the HED chapter of the 2005 TRED (USEPA 2005d), in mammals, technical flumiclorac-pentyl has low acute toxicity via the oral, dermal and inhalation routes of e xposure. It is a slight eye irritant and is a dermal sensitizer. Flumiclorac-pentyl has low toxicity potential following long-term exposures. In the rat, the kidney is a potential target organ at hi gh dose levels. Effects included urinary incontinence, increased water consump tion, increased urine volume, increased kidney weights in the females, and increased squamous ep ithelial cells in urinary sediment and increased kidney weights in the males. Nephropathy was evident in male rats in a two-generation reproduction study at high doses. Fl umiclorac-pentyl did not cause developmental toxicity in rat or rabbit fetuses and did not adversely affect reproductive parameters in rats in a reproduction study. No evidence of neurotoxicity or carcinogenicity was observed.

No mortality was observed in acute oral-dose or subacute dietary avia n studies. Reduced egg laying an regressed ovaries and sm all testes were observed in th e chronic study with the mallard

duck. There were no adverse effects observe d in the chronic bobwhite quail study.

Based on the degradation of parent flumiclor ac-pentyl to IMCA and IMCA’s potential for mobility in soils, a seedling emergence limit test was conducted using IMCA. The concentration of IMCA used in this study was based on the ma ximum application rate of flumiclorac-pentyl and the expected maximum concentration of th e degradate IMCA (53% of the flumicloracpentyl) to be present. The study was conduc ted with both a negative and solvent control (acetone), but percent emergence and shoot height comparisons between the negative control and treatment group is more appropriate than a co mparison using pooled controls. Based on a reduction in shoot lengths, the onion and oat we re statistically signifi cant compared to the negative control and the shoot height reductions ranged from -9.8 to 15% compared to the negative control. Decreases in seedling emergen ce for the limit concentration ranged from -12 to 12% compared to the negative control. No adverse effects were observed for phytotoxic symptoms. Dry weight was not measured in the seedling emerge nce study which is a sensitive endpoint for evaluating toxicity. The vege tative vigor study was conducted using parent flumiclorac-pentyl. The most sensitive sp ecies based on phytotoxicity was the tomato.

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### Table 6 Summary of sensitive toxicity endpoints for terres trial organisms under

consideration for use in risk assessment*

Common Name (Species)

TGAI /TEP End-point Mean Concentration and Effect Citation or

MRID /

Status Acute Toxicity

Classification

Mammals

Rat (Rattus norvegicus)

TGAI LD 50 > 5,000 mg/kg (mortality) 42169812/ Acceptable Practically

Nontoxic

Rat (Rattus norvegicus)

V-23031 0.83 EC LD 50 3,200 mg/kg (mortality) (females) 4,100 mg/kg (mortality) (males) 42169813/ Acceptable Practically

toxic

Rat (Rattus norvegicus)

TGAI 2 generation reproduction

NOAEL/

LOAEL 16/781 (M) 18/925 (F) mg/kg/day (increased kidney weight in males and females and nephropathy in males) 42169835/ Acceptable NA 1

Birds Bobwhite Quail (Colinus virginianus)

TGAI LD 50 > 2131 mg ai/kg-bw (no mortality) 42169802/ Acceptable Practically

Nontoxic

Bobwhite Quail (Colinus virginianus) /

Mallard Duck ( Anas platyrhynchos )

TGAI 8-day

LC 50 >5322 mg ai/kg-diet (no mortality) 42169803,

42169804/ Acceptable NA 1

Mallard Duck ( Anas platyrhynchos )

TGAI Chronic reproduction

NOAEC/

LOAEC 220/432 mg ai/kg-diet (Based on reduction in egg laying and

regressing ovaries and small testes) 42825806/ Acceptable NA 1

Terrestrial Invertebrates
Honey Bee (Apis mellifera)

TGAI LD 50 > 106 μg/bee (no mortality) 42169841/ Acceptable Practically

Nontoxic

Terrestrial Plants

EC 25 > 0.046 lb IMCA/Acre Seedling Emergence Seedling Emergence NOAEC < 0.046 lb IMCA/Acre 2 43258001/ Acceptable NA 1

EC 25 0.027 lb ai/Acre (Based on dry weight for lettuce) Vegetative vigor Vegetative vigor

NOAEC 0.00031 lb ai/Acre (Based on phytotoxicity for tomato) 43347401/ Acceptable NA 1

* Data in this table may be used in the risk assessment, but it will not necessarily be us ed to calculate risk quotients.

1 Toxicity Classification no t applicable for study.

2 Due to study conducted as limit test, a nd differences greater than 5% compared to control for both emergence and shoot height, a definitive NOAEC could not be determined

.



### 18 of 67

### 4.3. Incident Database Review

Incidents are maintained and catalogued by EFED in the Ecological Incident Information System (EIIS). There is only one ecological incident in the EIIS database that was associated in any way with flumiclorac-pentyl. In th at incident, there was damage to a soybean crop after application of a product containing flumiclora c-pentyl. However the report notes that the damage was believed to have been caused by residual contam ination from a prior use of the tank involving 2,4-D, and therefore was not due to flumiclorac-pe ntyl. Thus, the incident data give no evidence of this active ingredie nt causing any problems to non-target species.

4.4. Ecosystems Potentially at Risk

The ecosystems at risk are often extensive in scop e; therefore, it may not be possible to identify specific ecosystems during the development of a nation-wide ecological risk assessment. However, in general terms, terrestrial ecosystems potentially at risk could include the areas that are immediately adjacent to treated water that ma y receive drift or runo ff during flooding. Areas adjacent to the treated water could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or grasslands, woodlands, ri parian habitats and other uncultivated areas.

Aquatic ecosystems potentially at risk include tr eated water bodies and water bodies adjacent to or down stream from, the treated water and coul d include impounded bodies such as ponds, lakes and reservoirs, or flowing waterway s such as streams or rivers. For uses in coastal areas, aquatic habitat also includes marine ecosystems, including estuaries.

5. Assessment Endpoints

Assessment endpoints represent the ac tual environmental value that is to be protected, defined by an ecological entity (species, community, or other entity) and its attribute or characteristics (U.S. EPA 1998). For flumiclorac-pentyl, the ecologica l entities may include the following: birds, mammals, terrestrial-phase amphibian s, reptiles, freshwater fish a nd invertebrates, aquatic-phase amphibians, estuarine/marine fish and invertebrates, terrestrial plants, inse cts, and aquatic plants and algae. The attributes evaluated for each of these entities may include growth, reproduction,

and survival.

6. Conceptual Model

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

The conceptual model for flumiclorac-pentyl provides a written description and visual representation of the predicted relationships between flumiclora c-pentyl, potenti al routes of exposure, and the predicted effects for the assessment endpoint. Since flumiclorac-pentyl degrades to 2-chloro-4-fluoro-5-(3,4,5,6-tetra hydrophthalimido) phenoxyacetic acid (IMCA) and

19 of 67

### 20 of 67 this degradate is mobile and expected to be in the environment, both fl umiclorac-pentyl and its degradate IMCA will be assessed. A conceptual model consists of two major components: risk hypothesis and a conceptual diagram (U.S. EPA 1998).

6.1. Risk Hypothesis

A risk hypothesis describes the predicted re lationship among the stre ssor, exposure, and assessment endpoint response along with the rati onale for their selection. For flumicloracpentyl, the following overall ecologi cal risk hypothesis is being em ployed for this ecological risk

assessment:

Based on the application methods, mode of ac tion, fate and transport, and the sensitivity of non-target aquatic and terre strial species, flumiclorac-p entyl and its degradate IMCA has the potential to reduce surviv al and growth in non-target terrestrial plants when used

in accordance with the current label. Th ese non-target organisms include Federally listed threatened and endangered species as well as non-listed species. Based on flumiclorac-pentyl’s mode of action (light dependent pero xidizing herbicide), and known sensitivity of non-target aquatic and terrestri al species to this class of chemicals (Appendix C), flumiclorac-pentyl and its de gradate IMCA has the potential to reduce survival, growth and reproduction of non-ta rget aquatic and terrestrial animals.

The specific exposure routes quantitatively eval uated include, water con centrations and runoff and spray drift. The following hypothe ses reflect these exposure pathways.

• Flumiclorac-pentyl and IMCA concentrations in water may affect aquatic vertebrates, invertebrates, and plants.

• Flumiclorac-pentyl residues on plants and ot her dietary surfaces deposited with spray drift may affect terrestrial organisms, a nd runoff of IMCA may affect terrestrial plants during seedling emergence.

Conceptual Diagram

The environmental fate properties of flumiclorac- pentyl indicate that runoff, spray drift, and direct spray represent potential tr ansport mechanisms of flumiclor ac-pentyl or its degradates to aquatic and terrestrial habitats where non-target organism may be exposed. These transport mechanisms ( i.e ., sources) are depicted in the conceptual model below ( Figure 2 ) along with the receptors of concern and the potential attribute changes in the receptors due to exposures of flumiclorac-pentyl or degradates.Figure 2 Ecological ConceptualModel for Flumiclorac-pentylFlumichlorac-pentyl applied as a ground/aerial spray to an agricultural field,and its degradate IMCASource/TransportPathwaysDirectDepositionSprayDriftRunoffErosionSource/ExposureMediaExposureRouteReceptorsAttributeChangesTerrestrial FoodResidues (foliage,fruit, insects)UplandFoliage/SoilRiparian/WetlandFoliage/SoilReceiving WaterBody SedimentIngestionDirect contact/Root UptakeDirect contact/Root UptakeUptake/AdsorptionGil/IntegumentUptakeTerrestrialVertebratesTerrestrialUpland PlantsWetland/Riparian PlantsAquaticPlantsAquaticVerts/InvertsIndividual AnimalsReduced survivalReduced growthReduced Reproduction.Individual PlantsSeedling emergenceVegetative vigorPlant PopulationReducedPopulationGrowthIndividualVerts/InvertsReduced survivalReduced growthReducedReprod.Stressor21 of 67

### 7. Analysis Plan

In order to address the risk hypot hesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecol ogical effects of flumic lorac-pentyl and IMCA are characterized and integrated to assess the risks. This is accomplished using a risk quotient (ratio of exposure concentrati on to effects concentration) ap proach. Although risk is often defined as the likelihood and magnitude of advers e ecological effects, the risk quotient-based approach does not provide a quantitative estimate of likelihood and/or magnitude of an adverse effect. However, as outlined in the Overvi ew Document (U.S. EPA 2004), the likelihood of effects to individual organisms from particular uses of flumiclorac-pentyl is estimated using the probit dose-response slope and either the level of concern (discussed below) or the actual calculated risk quotient value.

This analysis plan will be re visited and may be revised dependi ng upon the data available in the open literature and the information submitted by the public in response to the opening of the Registration Review docket.

7.1. Stressors of Concern

As discussed above, flumiclorac-pentyl degrades into IMCA. Based on previous assessments ( e.g ., U.S. EPA 2005a), IMCA is a degradate of toxicological concern. Therefore, the focus of the assessment is expected to be the parent, flumiclorac-pentyl, and IMCA. However, the Agency will review all available current degrad ate ecotoxicity data to identify any additional

stressors of concern for the assessment.

In its ecological risk assessments, the Agency does not routinely include an evaluation of mixtures of active ingredients, either those mi xtures of multiple activ e ingredients in product formulations or those in the applicator’s tank. In the case of the product formulations of active ingredients (that is, a registered product contai ning more than one active ingredient), each active ingredient is subject to an indi vidual risk assessment for regula tory decision regarding the active ingredient on a particular use site. If eff ects data are available for a formulated product containing more than one active ingredient, the da ta may be used qualitatively or quantitatively in accordance with the Agency’s Overview Document and the Services’ Evaluation Memorandum (U.S. EPA 2004; U.S. FWS/NMFS 2004).

Available toxicity data for environmental mixtures of flumiclorac-pentyl with other pesticides will be presented as part of the ecological risk asse ssment. It is expected that the toxic effect of flumiclorac-pentyl, in combination with other pesticid es used in the environment, is likely to be a function of many factors including but not necessarily limited to: (1 ) the exposed sp ecies, (2) the

co-contaminants in the mixtur e, (3) the ratio of flumiclo rac-pentyl and co-contaminant concentrations, (4) differences in the pattern and duration of exposure among contaminants, and (5) the differential effects of ot her physical/chemical characterist ics of the receiving waters ( e.g. organic matter present in sediment and susp ended water). Quantitatively predicting the

combined effects of all these variables on mixture toxicity to any given ta xa with confidence is beyond the capabilities of the available data and methodologies. However, a qualitative

22 of 67

### discussion of implications of the available pes ticide mixture effects data on the confidence of

risk assessment conclusions will be addresse d as part of the uncertainty analysis.

7.2. Measures of Exposure

In order to estimate risks of flumiclorac-pentyl exposures in aquatic and terrestrial environments, all exposure modeling and resulting risk c onclusions will be made based on maximum application rates for flumiclo rac-pentyl. Measures of e xposure are based on aquatic and terrestrial models that predict estimated envir onmental concentrations of flumiclorac-pentyl using maximum labeled application rates and methods, as well as any mitigation measures specifically indicated on the label ( e.g. spray drift buffers).

PRZM and EXAMS are screening simulation models coupled with the in put shell pe5.pl (Aug 2007) to generate daily exposures and 1-in-10 year EECs of flumiclorac-pentyl that may occur in surface water bodies adjacent to application sites receiving flum iclorac-pentyl through runoff and spray drift. PRZM simulates pesticide application, movement and transformation on an agricultural field and the result ant pesticide loadings to a receiving water body via runoff, erosion and spray drift. EXAMS simulates the fate of the pesticide and resulting concentrations in the water body. The standard scenario used for ecological pesticide assessments assumes application to a 10-hectare agricu ltural field that drains into an adjacent 1-hectare water body that is 2 meters deep (20,000 m 3 

### volume) with no outlet. PRZM/EXAMS is used to estimate screening-level exposure of aquatic organisms to flumiclorac-pentyl. The measure of exposure for aquatic species is the 1-in- 10 year return peak or rolling mean concentration. The 1-in-10 year peak is used for estimating acute exposures ofdirect effects to aquatic organisms. The 1-in10-year 60-day mean is used for assessing chronic exposure to fish and aquatic-phase amphibians. The 1-in-10-year 21-day mean is used for assessing aquatic invertebrate chronic

exposure.

For ground and aerial spray appl ications, the T-REX model ( T errestrial R esidue EX posure model) is used to predict dietary exposure to flumiclorac-pentyl residues on foliar surfaces and insects using the Kenaga nomogram as modifi ed by Fletcher (Hoerg er and Kenaga 1972;

Fletcher et al. 1994). Exposure estimates for terrestrial an imals assumed to be in the target area or in an area exposed to spray drift are derived using the T-REX model. This model incorporates the Kenaga nomograph, as modified by Fletcher et al. (1994), which is base d on a large set of actual field residue data. The upper limit va lues from the nomograph represent the 95 th 

### percentile

of residue values from actual field measuremen ts (Hoerger and Kenega 1972). The Fletcher et
al. (1994) modifications to the Kenega nomograph are based on m easured field residues from 249 published research papers, including informa tion on 118 species of plants, 121 pesticides,

and 17 chemical classes.

Estimated Environmental Concentrations (EECs) for terrestrial plants inhabiting dry and wetland areas are derived using TerrPlant. This model uses estimates of pesticides in runoff and in spray drift to calculate EECs. EECs are based upon solubility, application rate and minimum incorporation depth.

The AgDRIFT spray drift model is used to assess exposures of terrestrial plants to flumicloracpentyl deposited on terrestrial habitats by spray drift. AgDRIFT will also be used to determine

23 of 67

### the appropriate PRZM/EXAMS parameter values for modeling the percen t drift corresponding to

the buffers indicated on the label.

7.3. Measures of Effect

Ecological effects data are used as measures of di rect and indirect effects to biological receptors. Data are obtained from registrant-submitted studies or from literature studies identified by ECOTOX. The ECOTOX database (U.S. EPA 2009) pr ovides more ecological effects data in an attempt to bridge existing data gaps. ECOTOX is a source for locating single chemical toxicity data and potential chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by the U.S. EPA, Office of Resear ch and Development,

and the National Health and Environmental Ef fects Research Laboratory's Mid-Continent Ecology Division. Based on the current search of flumiclorac-pentyl in the ECOTOX database, no acceptable open literature studies were found.

Information on the potential effects of flumiclorac- pentyl on non-target animals is also collected from the Ecological Incident Information System (EIIS). 2 

### The EIIS is a database containing adverse effect (typically mortalit y) reports on non-target organisms where such effects have been associated with the use of pesticides.

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

The assessment of risk for direct effects to non-target organisms makes the assumption that toxicity of flumiclorac-pentyl to birds is simila r to terrestrial-phase amphi bians and reptiles. The same assumption is made for fish and aquatic-phase amphibians.

The acute measures of effect used fo r animals in this assessment are the LD 50 

### , LC 50 

### and EC 50



### . LD stands for "Lethal Dose", and LD 50 

### is the amount of a material, given all at once, that is

estimated to cause the death of 50% of the test organisms. LC st ands for “Lethal Concentration”

and LC 50 

### is the concentration of a chemical that is estimated to kill 50% of the test organisms.

EC stands for “Effective Concentration” and the EC 50 

### is the concentration of a chemical that is estimated to produce a specific effect in 50% of the test organisms. Endpoints for chronic measures of exposure for listed and non-lis ted animals are the NOAEL/NOAEC and NOEC.

NOAEL stands for “No Observed-Adverse-Effect-Level ” and refers to the hi ghest tested dose of a substance that has been reported to have no harm ful (adverse) effects on test organisms. The NOAEC ( i.e. , “No-Observed-Adverse-Effect-Concentration” ) is the highest test concentration at

which none of the observed effects were statistically different fr om the control. The NOEC is

the No-Observed-Effects-Concentration. Fo r non-listed plants, only acute exposures are assessed ( i.e. , EC 25 

### for terrestrial plants and EC 50 

### for aquatic plants); for listed plants either the

NOAEC or EC 05 

### is used.

2 http://www.epa.gov/oppefed1/genera l/databasesdescription.htm#eiis



### 24 of 67

### 7.4. Integration of Exposure and Effects

Risk characterization is the integration of e xposure and ecological effects characterization to determine the potential ecological risk from the us e of flumiclorac-pentyl as a herbicide and the

likelihood of direct and indirect e ffects to non-target organisms in a quatic and terrestrial habitats. The exposure and toxicity effects data are integrated in order to evaluate the risks of adverse ecological effects on non-target spec ies. For the assessment of flum iclorac-pentyl risks, the risk quotient (RQ) method is used to compare exposur e and measured toxicity values. EECs are divided by acute and chronic toxicity values. The resulting RQs are then compared to the Agency’s Levels of Concern (LOCs) (U.S. EPA 2004) . These criteria are used to indicate when flumiclorac-pentyl’s uses, as directed on the label, have the potential to cause adverse direct or indirect effects to non-target organisms. In addition, incident data from the EIIS will be considered as part of th e risk characterization.

7.5. Deterministic and Probabilistic Assessment Methods

The quantitative assessment of risk will primarily depend on the deterministic point-estimate based approach described in the risk assessment. An effort will be made to further qualitatively describe risk using probabilistic tools that the Agency has developed. These tools have been reviewed by FIFRA Scientific Advisory Panels 3 

### and have been deemed as appropriate means of refining assessments where deterministic approaches have identified risks.

7.6. Endangered Species Assessments

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

The assessment of effects associat ed with the registra tion of flumiclorac-pentyl is based on an

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

evaluate direct or indi rect effects. The Agency’s appro ach to defining the action area under the provisions of the Overview Document (U.S. EPA 2004) considers the results of the risk assessment process to establish boundaries for that action area with the understanding that exposures below the Agency’s defined LOCs constitute a no-effect threshold. For the purposes of this assessment, attention will be focused on the footprint of the action (i.e., the area where flumiclorac-pentyl application occurs), plus all areas where offsite transport (i.e., spray drift, runoff, etc.) may result in potential exposur e that exceeds the Agency’s LOCs. Specific measures of ecological effect that define the action area for listed species include any direct and indirect effects and/or potential modification of its critical habitat, including reduction in survival, growth, and reproduction as well as the full suite of subl ethal effects available in the effects literature. Therefore, the action area ex tends to a point where environmental exposures are below any measured lethal or sublethal effect threshold for any biological entity at the whole

3 http://www.epa.gov/scipoly/sap/index.htm



### 25 of 67

### organism, organ, tissue, and cellula r level of organization. In situ ations where it is not possible to determine the threshold for an observed effect, the action area is not spatially limited and is

assumed to be the entire United States.

7.7. Preliminary Identification of Data Gaps

7.7.1 Fate

• Aerobic aquatic metabolism study (Guideline 8 35.4300). This study is needed to assess the degradation of flumiclorac-pentyl and the fo rmation and degradation of the IMCA in the aquatic environment.

• According to EFED’s BEAD Laboratory contac t a method for detecting the parent and IMCA in soil was submitted by the registrant (MRID 42825835). However, an independent laboratory validation (ILV) of the method was not completed ( Guideline Number: 

### 835.6100 )



### .

• The BEAD Laboratory has no record of a me thod being submitted by the registrant for detecting the parent and IMCA in water ( Guideline Number: 

### 835.6100 )



### .

No measured organic carbon part itioning coefficient (Koc or Kd) data were available for flumiclorac-pentyl or flumiclorac-acid (IMCA). However, because of the instability of the parent these data would be of limited utility.

7.7.2 Effects

Although many submissions have been made to provi de data on the effects of flumiclorac-pentyl to aquatic and terrestrial organisms, several data gaps still exist. Table 7 and Table 8 summarize the terrestrial and aquatic data, respectively, subm itted and required to a ssess the ecological risk from the use of flumiclorac-pentyl to control terrestrial vegetation. Data gaps include the following:

• avian acute oral toxicity (Guideline 850.2100) study with a passerine species,

• early life-cycle freshwater fi sh toxicity study (Guideline 850.1400) under UV enhanced light with the fathead minnow (Study previous ly required under GDCI-128724-26284, but not yet submitted)

• Tier II acute non-vascular aquatic plant gr owth (Guideline 850.5400) with the degradate 2- chloro-4-fluoro-5-( 3,4,5,6-tetrahydrophthalimido) phenoxya cetic acid (IMCA) for three species of non-vascul ar aquatic plants

• aquatic invertebrate life-cycle freshwater (Guideline 850.1300) using the degradate IMCA

with Daphnia magna

• aquatic invertebrate life-cy cle saltwater (Guideline 850.1350) using the degradate IMCA with mysid shrimp

• Tier II seedling emergence toxicity study (Guideline 850.4225) using the degradate IMCA with 10 species of terrestrial plants

A whole sediment acute freshwat er invertebrate study would be required based on a half-life in sediment less than 10 days in the aerobic so il metabolism study (7.3 – 8.04 days) and a log Kow of 4.99. This data requirement is not requested at this time since the parent flumiclorac-pentyl compound is unstable (a Kd study was not required due to instability), and the degradate being

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### mobile in soil. Also, flumiclorac-pentyl has low bioconcentration potential based on the fish bioconcentration study (372X, whole fish) (Pes ticide Fact Sheet: Flumiclorac-pentyl, 11/18/1994).

Table 7 Available Ecological Effects Data fo r Terrestrial Plants and Animals Exposed to Flumiclorac-pentyl and Remaining Data Gaps

Guideline Description Species TGAI

or TEP MRID/

Accession Classification Data Gap? Comments

850.2100 Avian oral toxicity Bobwhite Quail TGAI 42169802 Acceptable Yes*

Bobwhite

Quail TGAI 42169803 Acceptable 850.2200 Avian dietary toxicity Mallard Duck TGAI 42169804 Acceptable No

Bobwhite

Quail TGAI 42825805 Acceptable 850.2300 Avian reproduction

Mallard Duck TGAI 42825806 Acceptable No

850.3020 Honeybee acute contact toxicity Honeybee TGAI 4216 9841 Acceptable No Avian acute oral toxicity data

are not available for passerines, which are required

under the new 40 CFR Part 158. An acute oral toxicity study using passerines must be

submitted to fulfill this data requirement.

123.1 (b) Vegetative Vigor –

Tier II Corn, oat, onion, perennial,

ryegrass, soybean,

tomato, cucumber, lettuce, radish and cabbage TEP 43347401 Acceptable No

122.1 Seedling Emergence –

Tier I Cabbage,

corn, cucumber, lettuce, oat, onion,

ryegrass, soybean,

tomato and turnip IMCA 432580-01 A cceptable for

Tier I Yes* If pesticide is a know phytotoxin, a Tier II seedling emergence study is required

under the new 40 CFR Part

158. Also, a definitive

NOAEC could not be

determined from the Tier I study. Effects greater than 5% were observed for emergence

and shoot height, and the

onion and oat were statistically significant ( p <0.05) compared to negative control. Risk to listed species

can not be evaluated with the

Tier I data.
* Data Call In for passerine study and Tier II seedling emergence requested



### 27 of 67

### Table 8 Available Ecological Effects Data fo r Aquatic Animals Expo sed to Flumicloracpentyl and Remaining Data Gaps

Guideline Number Description Species TGAI/

TEP MRID/

Accession Classification Data Gap? Comments

Bluegill

Sunfish TGAI 42169806 Supplemental 850.1075

Freshwater fish –

Acute toxicity

Data needed for 1

coldwater species and 1 warmwater species. Data

needed for TEP needed if applied directly to water,

maximum EEC ≥ 0.5 LC 50 , or end product enhances toxicity Rainbow

Trout TGAI 42169807 Supplemental Yes 1 The exposure concentrations in

most of the tests is uncertain due to

1) Test solution appearance were

not reported for these studies.

Similar concentrations in other

studies reported presence of precipitates in test solution,

therefore the presence of precipitates in this study can not be precluded. Analytical methods to remove potential precipitates in the test solutions prior to analysis were

not reported. Therefore, the true

exposure concentration is not

known in submitted tests.

850.1075

Estuarine/Marine

fish – Acute toxicity

Data needed for 1 species. Data needed for TEP if applied directly to water, maximum

EEC ≥ 0.5 LC 50 , or end

product enhances toxicity. Sheepshead

Minnow TGAI 42825809 Supplemental Yes 1 Based on the presence of precipitate in the test solution, and analytical methods to remove this precipitate prior to analysis were

not reported, the true exposure

concentration is not known in

submitted test.

850.1010

Freshwater

invertebrates – Acute toxicity 2 Waterflea TGAI 42169808 Supplemental Yes 1 Based on the presence of precipitate in the test solution, and analytical methods to remove this precipitate prior to analysis were

not reported, the true exposure

concentration is not known in

submitted test.

Eastern oyster (shell deposition) TGAI 00103310 Supplemental Yes 4 850.1025, 850.1035, 850.1045, 850.1055

Estuarine/Marine

invertebrates – Acute toxicity 3

Mysid Shrimp TGAI 42825810 Acceptable No The oyster shell deposition study had limited growth in the control,

dissolved oxygen concentration below 60% of saturation, substantially decreasing test concentration, and the presence of

precipitate in test solution and analytical methods to remove precipitate prior to analysis not reported. Therefore, true exposure

concentration is not known, and toxicity could not be assessed due to control shell deposition below guideline minimum acceptability.



### 28 of 67Guideline Number Description Species TGAI/

TEP MRID/

Accession Classification Data Gap? Comments

850.1300

Freshwater

invertebrate – life cycle test

Data required for 1 species. No data submitted Yes* Freshwater invertebrate life-cycle toxicity data are required under the

new 40 CFR Part 158. The aerobic soil half-life for flumiclorac-pently and IMCA was 7-8 days. IMCA is

mobile and expected to enter the aquatic environment. The persistence of IMCA in the aquatic environment is not known, therefore chronic exposure could

occur.

850.1350

E/M invertebrate – Life Cycle 5 No data submitted Yes* The aerobic soil half-life for flumiclorac-pently and IMCA was

7-8 days. IMCA is mobile and

expected to enter the aquatic environment. The persistence of IMCA in the aquatic environment

is not known, therefore chronic exposure could occur. The LC 50 for the acute mysid study was 0.11 mg/L. Measured test concentrations ranged from 28 –

53% of nominal. Low measured

test concentrations believed to bedue to degradation of flumicloracpentyl, therefore toxicity could be due to the degradate IMCA.

850.1400

Freshwater fish – early life stage test 6 No data submitted Yes* *Freshwater fish early life-cycle toxicity data are not available for fish, which are required under the

new 40 CFR Part 158. A DCI was

issued in 2006 for an early lifecycle toxicity study under UV enhanced lighting for the fathead

minnow. This DCI was issued because flumiclorac-pentyl is an

LDPH chemical and enhanced toxicity could be observed under natural sunlight.

850.1400

E/M fish – early life stage test 7 No data submitted Pending Not anticipated at this time due to

LC 50 being greater than reported water solubility and the predicted

EEC is < 0.01 of acute LC 50

.
850.1500

Freshwater Fish –

life cycle test 8 No data submitted Pending Not anticipated at this time due to

LC 50 being greater than reported water solubility, flumiclorac-pentyl is not applied to water, and the fate of flumiclorac-pentyl



### 29 of 67Guideline Number Description Species TGAI/

TEP MRID/

Accession Classification Data Gap? Comments

850.1500

E/M Fish – life cycle test 9 No data submitted Pending Not anticipated at this time due to

LC 50 being greater than reported water solubility and the predicted

EEC is < 0.01 of acute LC 50

.
850.1735

Whole sediment

acute freshwater

invertebrate 10 No data submitted Pending Not required at this time, due to low bioconcentration potential of flumiclorac-pentyl and instability of parent flumiclorac-pentyl and its

degradates being mobile in soils.

850.1740

Whole sediment

acute marine

invertebrates 11 No data submitted Pending Not anticipated at this time due to flumiclorac-pentyl not applied to

water or expected to enter the aquatic environment in high

concentrations

Whole sediment

chronic

invertebrate

freshwater and

marine 12 No data submitted Yes The environmental degradation half-lives are less than 10 days.

No data are needed.

850.5400 Algal toxicity 13 Green Algae IMCA 43240800 Acceptable Yes* Only one species was tested (green algae), and testing is required for

blue-green alg ae, marine and freshwater diatoms. Testing with the degradate IMCA is requested, based on degradation of flumiclorac-pentyl and mobility of

IMCA.

850.4400 Aquatic plant

toxicity test Duckweed IMCA 4325 1201 Acceptable No

* Data Call-In for study requested Abbreviations: E/M = estuarine/marine; TEP=typical en d use product; TGAI=technical grade active ingredient; IMCA = degradate of flumiclorac-pentyl

1- Due to the supplemental classification of these studies, a data gap technically exists for these guidelines. The studies are classified as supplemental based on the presence of precipitate in the test solutions. Analytical methods to remove potential precipitates in the test solutions prior to analysis were not reported. In addition, the freshwater fish studies did not report test solution appearance. No new studies are requested at this time due to the existing studies providing adequate information to evaluate risk. Studies can be upgraded with the submission of acce ptable test solution appear ance (freshwater fish) and analytical methods (all studies).

2- Data needed for 1 species. Data needed for TEP n eeded if applied directly to water, maximum EEC ≥ 0.5

LC 50 , or end product enhances toxicity

3- Data required for 1 mollusk and invertebrate. Data ne eded for TEP if applied directly to water, maximum

EEC ≥ 0.5 LC 50 , or end product enhances toxicity.

4- Due to the supplemental classification of this study, a data gap technically exists for this guideline. This study is supplemental due to limited growth in the control, dissolved oxygen concentration below 60% of saturation, substantially decreasing test concentration, and the presence of precipitate in test solution and



### 30 of 67analytical methods to remove precipitate prior to analysis not reported. Due to these study deficiencies this study can not be upgraded. The acceptable acute mysid study will be used to evaluate risk.

5- Data are required for 1 species when the chemical is applied directly to the E/M environment, acute LC 50 < 1 mg/L, or the EEC is ≥ 0.01 of acute LC 50

. 6- Data on 1 species are needed on a species with acute data.

7- Data are required for 1 species when the chemical is applied directly to the E/M environment, acute LC 50 < 1 mg/L, or the EEC is ≥ 0.01 of acute LC 50

. 8- Data are required for 1 species when applied directly to water or if EEC is ≥ 0.1 of NOEL in fish early life stage, 2) if studies suggest reproduction physiology may be affected.

9- Data are required for 1 species when applied directly to water or if EEC is ≥ 0.1 of NOEL in fish early life stage, 2) if studies suggest reproduction physiology may be affected.

10- Data are required when half-life of pesticide in sediment ≤ 10 days and 1) the Kd is ≥ 50, 2) the KOC

≥ 1000, or the KOW ≥ 1000.

11- Data are required for 1 species for uses with direct application to E/M water. Data are required when halflife of pesticide in sediment ≤ 10 days and 1) the Kd is ≥ 50, 2) the KOC ≥ 1000, or the KOW ≥ 1000.

12- Data required if EEC> 0.1 of acute LC 50 and the half-life > 10days and if any of the following exist: the

low Kow ≥ 3 or the K OC ≥ 1000. Data required for E/M when a pplied directly to E/M environment.

13- Data required when chemical is known phytotoxin (e.g. herbicide).



### Due to the uncertainties in the actual water concentr ations of the aquatic toxi city studies, with the exception of the acute mysid shrimp toxicity study, these studies ar e classified as supplemental. Studies, except for acute oyster toxicity study, can be upgraded to acceptable if documentation can be provided showing adequate analytical methods were used (fil tering or centrifuging of test solutions prior to analysis). The rainbow trout and bluegill sunfish studies can also be upgraded provided documentation of test solution appearance as well as the use of adequate analytical

methods.

Avian Acute Oral Toxicity (Gui deline 850.2100): Passerine Species

Acceptable acute avian oral toxi city data were submitted for e xposures of bobwhite quail to flumiclorac-pentyl; however, data are not available for passerine s, which are required under the new 40 CFR Part 158 data requirements for c onventional pesticides (72 FR 60934; USEPA 2007b). The new Part 158 data requirements spec ify that acute avian oral toxicity data be

submitted for either a mallard duck or bobwhite quail AND a passerine species. EFED suggests that SRRD request submission of a passerine stu dy protocol for review by the Agency prior to initiation of this study. If oral acute toxicity data are not submitted for passerines, EFED will assume acute risk for passerine species.

Early Life-Cycle Toxicity to Freshwater Fish (Guideline 850.1400): Testing under enhanced UV lighting with the Fathead Minnow

Enhanced toxicity to organisms may occur due to flumiclorac-pentyl being a light dependant peroxidizing herbicide. Therefor e an early life-cycle study with fl umiclorac-pentyl is requested. Due to structurally similarities to parent flumic lorac-pentyl, the major degradate IMCA may also be phototoxic. This enhanced toxicity is not limited to fish, but could occur in aquatic invertebrates, plants, and terr estrial birds and mammals. This study was already required in GDCI-128724-26284. The registrant Valent USA Cor poration has joined the registrant light dependent peroxidizing herbicide workgroup (L DPH WG). This LDPH WG is currently

31 of 67

### working with EFED in implementing toxicity testi ng to evaluate chronic fi sh toxicity from light dependent peroxidizing herbicid es under enhanced UV lighting.

Aquatic Freshwater and Estuarine-marine Invertebrate Life Cycle (850.1300 and 1350) with Daphnia magna and the Mysid Shrimp

Freshwater invertebrate life-cyc le toxicity data are required u nder the new 40 CFR Part 158. The

aerobic soil half-life for flumiclorac- pentyl and 2-chloro-4-fluoro-5-(3,4,5,6- tetrahydrophthalimido) phenoxyacetic acid (IMCA) was 7-8 days. IMCA is mobile and expected to enter the aquatic environment. The persistence of IMCA in the aquatic environment is not known, therefore chronic exposure could o ccur. The aerobic soil half-life for flumicloracpently and IMCA was 7-8 days. IMCA is mobile and expected to enter the aquatic environment. The degradation or persistence of IMCA in the aquatic environment is not known, therefore IMCA is assumed to be persistent. Therefore, an aquatic freshwater in vertebrate life cycle study

with Daphnia magna using the degradate IMCA is requested.

Although the registrant requested a data requirement waiver for the estuarine-marine invertebrate life-cycle study (Guideline 850.1350) based on the pred icted EEC concentration in water and the Ecological Effects Branch (now EFED) recommende d this request be granted, this study is now being requested. In addition to the fate of fl umiclorac-pentyl and IMCA described above, the

LC 50 

### for the acute mysid study was 0.11 mg a.i./L. Measured test concentrations in this acute mysid toxicity study ranged from 28 – 53% of no minal. The low measured test concentrations according to the study author’s was believed to be due to degradation of flumiclorac-pentyl. Therefore, the toxicity observed could be due to the degradate IMCA. According to the 40 CFR part 158, data is required on estu arine-marine species if the acut e LC50 is less than 1 mg/L, and the pesticide half-life in water is greater than f our days. Therefore, an aquatic estuarine-marine invertebrate life cycle stu dy with the mysid shrimp ( Americamysis bahia ) using the degradate IMCA is requested.

Aquatic Plant Studies (850.5400)

Toxicity data for some non-vasc ular aquatic plants ar e not available, as only a study with the green algae was submitted. Based on the 40 CFR Pa rt 158 data requirements, Tier II non-target aquatic plant data are required for known phytotoxins (herbicides) . Based on the degradation of flumiclorac-pentyl to IMCA and IMCA’s mobility in soils, this additional testing is requested with the degradate IMCA and not parent flumiclora c-pentyl. This data gap must be filled, and non-target aquatic plant data for algae plan ts (OPPTS Guideline 850.5400) are required for the degradate IMCA at the Tier II level at this ti me. In the absence of Tier II data, EFED will assume risk to non-vascular aquatic plants.

32 of 67

### Terrestrial Plant Toxicity, Ti er II Seedling Emergence (850.4225)

A Tier I seedling emergence limit test was conduc ted using IMCA. Since toxicity greater than 25% was not observed, the results of the study did not trigger a Tier II study. Based on a reduction in shoot lengths, the onion and oat we re statistically signifi cant compared to the negative control and the shoot height reductions ranged from -9.8 to 15% compared to the negative control. Decreases in seedling emergen ce for the limit concentration ranged from -12 to 12% compared to the negative control. No adverse effects were observed for phytotoxic symptoms. Dry weight was not measured in the seedling emerge nce study which is a sensitiveendpoint for evaluating toxicity. Based on the 40 CFR Part 158 data requirements, Tier II nontarget terrestrial plant data ar e required for known phytotoxins (herbi cides). This data gap must be filled, and non-target terres trial plant data (OPPTS Guidel ine 850.4225) are required for the degradate IMCA at the Tier II level at this ti me. A Tier II study will allow for the determination of a no observed adverse effect concentration (NOAEC) or EC 05 

### toxicity value. A NOAEC or

EC 05 

### is needed to reliably determine effects to listed terrestrial plants.

Aerobic Aquatic Metabolism (835.4300)

Since flumiclorac-pentyl degrades to IMCA and this degradate is expected to enter the aquatic environment, exposure from IMCA to aquatic organisms will be assessed. The persistence of IMCA in the aquatic environment is not known, th erefore IMCA is assumed to be persistent. This study is needed to assess the degradation of flumiclorac- pentyl and the formation and degradation of the IMCA in the aquatic environment.

Water Analytical Method and ILV for Water and Soil Method (MRID 42825835)

Registrants are required to submit an analytical met hod for detecting and measuring the quantity of each active ingredient in their products. Validation da ta for both accuracy and precision should be submitted for all methods. Analytical methods for the active ingr edient may be validated by EPA laboratories at the time the product chemistry data are reviewed.



### 33 of 67

### 8. Data Call In Tables

Guideline Number: 850.2100 Study Title: Avian Oral Toxicity (Passerine Species with TGAI)

Rationale for Requiring the Data

No data for passerine species are available. A lthough the submitted avian acute data suggest that flumiclorac-pentyl is practically nontoxic to the bobwhite quail, toxicity data for game birds may not reflect risks to passerine birds which have been identified to be more sensitive to pesticides in some cases than the Bobwhite Quail or Mallard Duck. Therefore, additional data are ne eded to accurately assess risks to these species. Specifically, data are require d on one passerine species in additio n to either one waterfowl species or one upland game bird species for terrestrial, aquatic , forestry, and residential outdoor uses. No species is recommended at this point, and a protocol should be submitted for review prior to test initiation.

Practical Utility of the Data

How will the data be used? The passerine acute toxicity data are needed for futu re regulatory decisions, and for endangered species assessments. The data will allow the Agency to better assess the risks to these organisms, including the likelihood of potential risks to endangered species, eith er by direct effects or by indirect effects such as reducing food sources to listed predators and scavengers. Results of this study would be used to calculate acute risks to passerine species from exposure to flum iclorac-pentyl and to identify whether current labeling is appropriate and whether fu rther mitigation is necessary.

How could the data impact the Ag ency’s future decision-making? If the data indicate that flumiclorac-pentyl poses a significant acute risk to upland game or passerine birds, the Agency may explore additional decision options to minimize the risk of flumiclorac-pentyl to these species. If future endangered species risk assessments are performed without thes e data, the Agency would have to assume that flumiclorac-pentyl "may affect" passerine birds directly and other endangered species indirectly through loss of prey. The lack of these da ta will limit the flexibility the Agency and registrants have in complying with the Endangered Species Act an d could result in unnecessary use restrictions, and the use of flumiclorac-pentyl may need to be restricted in areas where endangered species occur unless these data are provided.



### 34 of 67For IMCA Degredate

Guideline Number: 850.1300 Study Title: Aquatic Invertebrate Life Cycle (Freshwater) Rationale for Requiring the Data

Freshwater invertebrate life-cycle toxicity data are requ ired under the new 40 CFR Part 158. The aerobic soil half-life for flumiclorac-pently and 2-chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido) phenoxyacetic acid (IMCA) was 7-8 days. IMCA is mobile and expected to enter the aquatic environment. The persistence of IMCA in the aquatic environment is not known, therefore chronic exposure could occur. Therefore, a chronic life cycle toxicity study with IMCA is requested for the Daphnia magna.

How will the data be used? This additional toxicity data will allow the Agency to be tter refine the risks to these organisms, including the likelihood of potential risks to endangered species, eith er by direct effects or by indirect effects such as reducing food sources to listed predators and scavengers. Results of this study would be used to calculate chronic risks to aquatic species from exposure to IMCA and to identify whether current labeling is appropriate and whether furt her mitigation is necessary.

How could the data impact the Ag ency’s future decision-making? If the data indicate that IMCA poses a significant chr onic risk to aquatic invert ebrates, the Agency may explore additional decision options to minimize the risk of IMCA to these species. If future endangered species risk assessments are performed without these data, the Agency might have to assume that IMCA "may affect" aquatic invertebrates directly and other endangered species indi rectly through loss of prey. The lack of these data will limit the flexibility the Agency and registrants have in complying with the Endangered Species Act and could result in unnecessary use restrictio ns, and the use of IMCA may need to be restricted in areas where endangered species occur unless these data are provided.



### 35 of 67For IMCA Degredate

Guideline Number: 850.1350 Study Title: Aquatic Invertebra te Life Cycle (Estuarine-marine) Rationale for Requiring the Data

The aerobic soil half-life for flumiclorac-pently and 2-chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido) phenoxyacetic acid IMCA was 7-8 days. IMCA is mobile and expected to enter the aquatic environment. The persistence of IMCA in the aquatic environment is not know, therefore chronic exposure could occur.

The LC 50 for the acute mysid study was 0.11 mg/L. Measured test concentrations ranged from 28 – 53% of nominal. Low measured test concentrations believed to be due to degradation of flumiclorac-pentyl, therefore toxicity could be due to the degradate IMCA. According to the 40 CFR part 158, data is required on estuarine-marine species if the acute LC 50 is less than 1 mg/L, and the pestic ide half-life in water is greater than four days. Therefore, an aqua tic estuarine-marine invertebrate lif e cycle study with the mysid shrimp ( Americamysis bahia ) using the degradate IMCA is requested. Practical Utility of the Data

How will the data be used? This additional toxicity data will allow the Agency to be tter refine the risks to these organisms, including the likelihood of potential risks to endangered species, eith er by direct effects or by indirect effects such as reducing food sources to listed predators and scavengers. Results of this study would be used to calculate chronic risks to aquatic species from exposure to IMCA and to identify whether current labeling is appropriate and whether furt her mitigation is necessary.

How could the data impact the Ag ency’s future decision-making? If the data indicate that IMCA poses a significant chr onic risk to aquatic invert ebrates, the Agency may explore additional decision options to minimize the risk of IMCA to these species. If future endangered species risk assessments are performed without these data, the Agency might have to assume that IMCA “may affect" aquatic invertebrates directly and other endangered species indi rectly through loss of prey. The lack of these data will limit the flexibility the Agency and registrants have in complying with the Endangered Species Act and could result in unnecessary use restrictio ns, and the use of IMCA ma y need to be restricted in areas where endangered species occur unless these data are provided.



### 36 of 67For IMCA Degredate

Guideline Number: 850.5400, 122-2 Study Title: Aquatic Plant- Freshwater Diatom (usually Naviculla sp.)

Guideline Number: 850.5400, 122-2 Study Title: Aquatic Plant-Marine Diatom Skeletonema costatum

Guideline Number 850.5400, 122-2 Study Title: Aquatic Plant-Cyanobacteria Anabaena flos-aquae Rationale for Requiring the Data Only one non-vascular species was submitted, the freshwater green algae, Selenastrum capricornutum

. There are a total of four different non-vascular aquatic plant speci es that are usually tested. Additional aquatic plant toxicity data are currently needed to assess the risk of the degradate IMCA to non-target aquatic plants. Plants form the basis of most habitats and significantly contribute to overall environmental quality, and therefore a solid understanding of the potential risks to non-target plants is essential for sound environmental management.

Flumiclorac-pentyl is applied to corn, soybeans, and cotton. Parent flumiclorac-pentyl is not expected to be present in aquatic systems at high concentrations, but its major degradate IMCA is expected to be in aquatic environments based on its mobility, and may be phytot oxic. Since parent flumiclorac-pentyl is a light dependant peroxidizing herbicide and IMCA is structurally similar to parent flumiclorac-pentyl, enhanced toxicity under natural sunlight is expected to organisms. Testing with the major degradate IMCA is requested. Tier II study design is required for chemic als that are know phytotoxins (herbicides), therefore Tier II study design is requested at this time for all species. A Tier II study will allow for the determination of a no observed adverse effect concentration (NOAEC) or EC 05 toxicity value.

Practical Utility of the Data

How will the data be used? The data will be used to estimate potential risks to non-target aquatic plants, including the likelihood of potential risks to endangered species, either by direct effects or by indirect effects, and to reduce uncertainties associated with the current ecological risk assessment. By refining the assessment, the Agency will be able to determine whether current labeling is appropriate and whether furt her mitigation is necessary.

How could the data impact the Ag ency’s future decision-making? These data, once submitted, will allow the Agency to characterize the risk of flumiclorac-pentyl and its degradate IMCA to aquatic ecosystems. Primary producers (i.e. plants) provide oxygen, food and habitat vital to ecological processes. Theref ore, a solid understanding of the potential risks to plants is essential in order to assess the environmental risks the use of flumiclorac-pentyl may pose. If the data indicates that flumiclorac-pentyl poses significant risks to these plan t species, the Agency may explore additional decision options to minimize the risks to these species. The lack of these data will limit the flexibility the Agency and registrants have in complying with the Endangered Species Act and could result in use restrictions for flumiclorac-pentyl which may otherwise be avoided, or which are unnecessarily severe.



### 37 of 67For IMCA Degradate

Guideline Number: 850.4225 Study Title: Tier II Terrestrial Plan t Seedling Emergence Toxicity Test Rationale for Requiring the Data Data regarding the toxicity of flumiclorac-pentyl to terrestrial plant seedling emergence are insufficient to

determine a no effect concentration. There are k nown phytotoxic effects (seedling emergence and shoot height) to some plants from flumiclorac-pentyl. Also, dry weight was not measured in the Tier I seedling emergence toxicity study, and dry weight is known to be a sensitive endpoint for evaluating toxicity. Practical Utility of the Data

How will the data be used? Seedling emergence data for terrestrial plants will be used to determine the potential for flumiclorac-pentyl to affect non-target plant species in the terrestrial environment.

How could the data impact the Agency’s future decision-making? If future endangered species risk assessments are perf ormed without these data, the Agency would have to presume risk to non-target terrestrial plants from use of flumiclorac-pentyl. Therefore, use of flumicloracpentyl and its formulated products may need to be restricted in areas where listed species could be exposed. The lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with the Endangered Species Act and could result in use restrictions for flum iclorac-pentyl that are unnecessarily severe.

Aerobic Aquatic Metabolism

Guideline Number: 835.4300 Study Title: Aerobic Aquatic Metabolism Rationale for Requiring the Data Aerobic aquatic metabolism studies facilitate an unde rstanding of a compound’s degradation in the water column or sediment under aerobic (oxygen-rich) conditions in the laboratory. These studies are generated by pesticide interaction with microorganis ms in a water/sediment system.

The requested data would allow EPA to refine its acute risk (mortality) and chronic risk (growth and reproduction) estimates for all aquatic and estuarine/marine organisms, and allow it to define an action area for endangered species. Risk mitigation strategies ( e.g. , determining maximum flumiclorac-pentyl application rate that results in an RQ below the LOC) cannot be evaluated without these data. Practical Utility of the Data

How will the data be used? No aerobic aquatic metabolism studies that track the formation and decline of flumiclorac-pentyl and its metabolites (primarily IMCA) are currently available. These data will be used to characterize the environmental fate of flumiclorac-pentyl. For quantita tive exposure estimation, these data will be used to determine appropriate inputs for simulation modeling.

How could the data impact the Agency’s future decision-making? Without these required data, the fate of flumiclorac-pentyl in aquatic environments cannot be fully characterized. The persistence of fl umiclorac-pentyl in these environm ents and the degradates to which aquatic organisms will be exposed is uncertain. In the absence of acceptable data, conservative assumptions will be made. If more refined conclusions are required for assessing risk to ecol ogical receptors, including endangered species, it will be assumed that unknown degradates are stable and of equal toxicity to the parent. Thus, use of flumiclorac-pentyl might need to be restricted in areas where endangered species could be exposed. The lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with the Endangered Species Act and could result in use restrictions for flumiclorac-pentyl which are unnecessarily severe.



### 38 of 67Guideline Number: 835.6100 Data requirement: Environmental Ch emistry Analytical Methods -- soil

Guideline Number: 835.6200 Data requirement: Environmental Ch emistry Analytical Methods -- water Rationale for Requiring the Data Independently validated analytical methods for residues in soil, water, and plant material (environmental chemistry methods) submitted by the registrant are us ed to evaluate analyses described in submitted environmental fate and ecological effects studies. Submitted analytical methods are also used by various federal, state, tribal, and local agen cies to detect and monitor residues th at are or are suspected to be in environmental compartments due to outdoor uses and acci dental releases. Therefor e, availability of these analytical methods is necessary to ensure the safety of those in proximity to releases of flumicloric-pentyl residues in the environment. Independent laboratory validations for submitted analytical methods are necessary to confirm the levels of detection and qu antitation reported in registrant-prepared validations.

Use of flumicloric-pentyl may cont aminate surface water due to runoff and drift of residues. This is especially true for poorly draining soils and soils w ith shallow ground water. Flumicloric-pentyl residues have a high potential for runoff for several weeks after application. Therefore, outside agencies may request analytical methods with which to monitor for flumiclori c-pentyl residues in water and in soil or sediment.

While analytical methods ( a.k.a. environmental chemistry methods) for flumicloric-pentyl residues in soil were submitted by the registrant; (MRID 42825835); they were not submitted fo r water. In addition, independent validations of the soils methods was not submitted. Therefore, independent validations of analytical methods for flumicloric-pentyl residues in so il and in water are required to support monitoring for flumicloric-pentyl residues and to evaluate submitted environmental fate and ecological effects data.

Practical Utility of the Data

How will the data be used?

In the absence of independently validated environmental chemistry methods, submitted environmental fate and ecological effects data may not be reviewable and entities outside the Agency may lack chemical-specific methods for analyses in environmental compartments. Independently validated environmental chemistry

methods will be used to evaluate the submitted enviro nmental fate and ecological effects data and will be made available to the public to support monitoring for flumicloric-pentyl residues.

How could the data impact the Agency’s future decision making?

Risk assessment conclusions could be altered if they are not supported by either study data or environmental monitoring detections that are based on independently validated environmental chemistry methods. Furthermore, while not directly related to Agency decision making, independently validated environmental chemistry methods are necessary to ensu re the safety of those in proximity to releases of flumicloric-pentyl

residues in the environment.



### 39 of 67

### 9. References

9.1. Open Literature

CFR 40. 2007. Code of Federal Regulati ons 40 Parts 150 to 189. Protection of the Environment. U.S. Government Printing Office.

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger. 1994. Literature review and evaluation of the EPA food-chain (Kenaga) nomogram, an instru ment for estimating pesticide residues on plants. Environ. Tox. Chem. 13:1383-1391.

Hoerger, F. and E. E. Kenaga, 1972. Pesticide Re sidues on Plants: Correlation of Representative

Data as a Basis for Estimation of th eir Magnitude in the Environment. In F. Coulston and F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ., Stuttg art, West Germany, pp. 9-28.

USEPA. 1993. Wildlife Exposure Factors Ha ndbook. EPA/600/R-13/187a, Office of Research and Development, Washington, D.C.

U.S. EPA. 1994. EEB Hazard Assessmen t Science Chapter V23031. DP 165814, 195820 and

199998. Office of Pesticide Pr ograms. Washington, D.C.

U.S. EPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Research and Development, Wash ington, D.C. EPA/630/R-95/002F. April 1998. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759

U.S. EPA. 2002. Guidance for Selecting Input Pa rameters in Modeling th e Environmental Fate and Transport of Pesticides, Version II . US Environmental Protection Agency, Washington DC. Online at: http://www.epa.gov/oppefed1/models water/input_guidance2_28_02.htm.

U.S. EPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Ag ency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

U.S. EPA. 2005a. Environmental Fate and Effects Science Chapter, Environmental Fate and Ecological Risk Assessment, Registrati on for New Use for Flumiclorac-pentyl

. PC Code 128724. DP Barcode D311964. October 31, 2005. Environmental Fate and Effects

Division. Office of Pesticide Programs. Washington, D.C.

U.S. EPA 2005b. Flumiclorac-pentyl: Tolerance Reassessmen t Decision for Low Risk Pesticide; Notice of Availability. EPA-HQ-OPP-2005-0229-0001. Oct ober 19, 2005. Office of Pesticide Programs. Washington, D.C.

40 of 67

### U.S. EPA 2005c. Report of the Food Quality Protection Act (FQPA) Tolerance Assessment Progress and Risk Management Decision (TRED)

. EPA-HQ-OPP-2005-0229-0002. September 15, 2005. Office of Pestic ide Programs. Washington, D.C.

U.S. EPA 2005d. HED Chapter of the TRED

. EPA-HQ-OPP-2005-0229-0003. September 15,

2005. Health Effects Division. Office of Pe sticide Programs. Washington, D.C.

U.S. EPA 2005e. Flumiclorac-pentyl Ch ronic Dietary Assessment for the TRED

. EPA-HQOPP-2005-0229-0004. September 15, 2005. Health Effects Division. Office of Pesticide Programs. Washington, D.C.

U.S. EPA 2005f. Flumiclorac-pe ntyl Residue Chem for the TRED

. EPA-HQ-OPP-2005-0229- 0005. September 15, 2005. Office of Pes ticide Programs. Washington, D.C.

U.S. EPA 2005g. Flumiclorac-pentyl TRED Product Chem Considerations

. EPA-HQ-OPP2005-0229-0006. September 15, 2005. Office of Pe sticide Programs. Washington, D.C.

U.S. EPA 2005h. Flumiclorac-pentyl Tier 1 Drinking Water Assessment

. EPA-HQ-OPP-2005- 0229-0007. September 15, 2005. Office of Pest icide Programs. Washington, D.C.

U.S. EPA 2005i. Flumiclorac-pent yl EFED Addendum No. 1 to MRID#42169844

. EPA-HQOPP-2005-0229-0008. September 15, 2005. Environm ental Fate and Effects Division. Washington, D.C.

U.S. EPA 2005j. Flumiclorac-pentyl EFED Addendum No. 1 to MRID 43304601

. EPA-HQOPP-2005-0229-0009. September 15, 2005. Environm ental Fate and Effects Division. Office of Pesticide Programs. Washington, D.C.

U.S. EPA. 2007a. Ecological Incident Information System. http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

U.S. EPA. 2007b. 40 CFR Part 158. Pestic ides; Data Requirements for Conventional

Chemicals: Final Rule. 72 FR 60934. October 26, 2007.

U.S. EPA. 2008. Usage/Use Report Package in Support of Registration Review for Flumicloracpentyl. September 2008. Biological and Economic Anal ysis Division. Office of Pesticide Programs. Washington, DC.

U.S. EPA 2009. ECOTOXicology Database. Office of Resear ch and Development National

Health and Environmental Effects Research Laboratory’s (NHEERL’s) Mid-Continent Ecology Division (MED). http://cfpub.epa.gov/ecotox/

U.S. Fish and Wildlife Service (USFWS) and Na tional Marine Fisheries Service (NMFS). 1998. Endangered Species Consultation Handbook: Procedures for Conducting Consultation

and Conference Activities Under Section 7 of the Endangered Sp ecies Act. Final Draft.

March 1998.

41 of 67

### U.S. FWS/NMFS. Letter providi ng an evaluation by the U.S. Fi sh and Wildlife Service and

National Marine Fisherie s Service of an approach to a ssessing the ecological risks of pesticide products. From Steve Williams and William Hogarth to Susan Hazen. January 26, 2004.

9.2. Submitted Fate Studies

Guideline: 72-6 Aquatic org. accumulation

------------------------------------------------------------------------------------- MRID: 42169809 Ohshima, M.; Mikami, N. (1991) Uptake, Depuration and Bio- concentration of ??carbon 14|-PH|-S-23031 to Bluegill Sunfish (Lepomis macrochirus): Lab Project Nu mber: ACC90001A. Unpub- lished study prepared by Sumitomo Chemical Co., Ltd. 41 p.

MRID: 42169810 Ohshima, M.; Mikami, N. (1991) Uptake, Depuration and Bio- concentration of ??carbon 14|-THP||-S-23031 to Bluegill Sunfish (Lapomis macrochirus): Lab Project Number: ACC90001B. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 41 p.

MRID: 42825812 Ohshima, M.; Mikami, N. (1993) Charact erization of (carbon 14) Residues in Bluegill Sunfish Treat ed with ((carbon 14)-PH)-S-23031: Lab Project Number: ACC90001-C: SAM-20-0031. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 127 p.

MRID: 42825813 Ohshima, M.; Mikami, N. (1993) Charact erization of (carbon 14) Residues in Bluegill Sunfish Treat ed with ((carbon 14)-PH)-S-23031: Lab Project Number: ACC90001-D: SAM-20-0032. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 147 p.

Guideline: 161-1 Hydrolysis

------------------------------------------------------------------------------------- MRID: 42169842 Horvath, M.; Korsch, B. (1991) A Hydrolysis Study of S-23031 Experimental Herbicide: Lab Project Number: 89- 0122. Unpublished study prepared by Ricerca, Inc. 295 p.

Guideline: 161-2 Photodegradation-water

------------------------------------------------------------------------------------- MRID: 42825824 Korsch, B.; Lee, D.; Rose, K.; et al. (1992) A Photolysis Study of (PH-(carbon 14))-S-23031 in Water at pH 5: Lab Project Number: 3314-91-0137-EF-001. Unpublished study prepared by Ricerca, Inc. 111 p.

MRID: 42825825 Korsch, B.; Lee, D.; Rose, K.; et al. (1992) A Photolysis Study of (TPH-(carbon 14))-S-23031 in Water at pH 5: Lab Project Number: 3314-91-0138-EF-001. Unpublished study prepared by Ricerca, Inc. 106 p.

Guideline: 161-3 Photodegradation-soil

------------------------------------------------------------------------------------- MRID: 42825826 Korsch, B.; Shah, J. (1992) A Photolysis Study of (P H-(carbon 14))-S-23031 on Soil: Lab Project Number: 3313- 91-0139-EF-001. Unpublished study prepared by Ricerca, Inc. 132 p.



### 42 of 67MRID: 42825827 Korsch, B.; Shah, J. (1992) A Photolys is Study of (TPH-(carbon 14))-S-23031 on Soil: Lab Project Number: 3313- 91-0140-EF-001. Unpublished study prepared by Ricerca, Inc. 128 p.

Guideline: 162-1 Aerobic soil metabolism

------------------------------------------------------------------------------------- MRID: 42169843 Hardies, D. (1991) An Aerobic Soil Metabolism Study with S-23031, an Experimental Herbicide, II. THP-?carbon 14|-S- 23031 as the Test Substance: Lab Project Number: 89-0119. Unpublished study prepared by Ricerca, Inc. 338 p.

MRID: 42169844 Hardies, D. (1991) An Aerobic Soil Metabolism Study with S-23031, an Experimental Herbicide, I. ?Ph-carbon 14|- S-23031 as the Test Substance: Lab Project Number: 89-0119. Unpub- lished study prepared by Ricerca, Inc. 291

p.

MRID: 43275103 Yamada, H. (1988) Preliminary Aerobic Soil Metabolism Study of S-23031: Lab Project Number: SAM-80-0003. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 21 p.

MRID: 43304601 Huhtanen, K. (1994) An Aerobic Soil Metabolism Study with S-23031: (THP-(carbon 14)) S-23031 as the Test Substance: Lab Project Number: 93/0106: 5711/93/0106/EF/001. Unpublished study prepared by Ricerca, Inc. 230

p.

Guideline: 162-2 Anaerobic soil metabolism

------------------------------------------------------------------------------------- MRID: 42825828 Rose, A. (1993) An Anaerobic Soil Metabolism Study with S-23031, an Experimental Herbicide, II (THP-(carbon 14))-S-23031 as the Test Substance: Response to EPA Review: Lab Project Number: 93-RES-009. Unpublished study prepared by Valent USA Corp. 13 p.

Guideline: 162-3 Anaerobic aquatic metab.

------------------------------------------------------------------------------------- MRID: 42825829 Hatzenbeler, C. (1992) An Anaerobic Aquatic Soil Metabo lism Study with (THP-(carbon 14))-S-23031: Lab Project Number: 91-0216: 3444-91-0216-EF-001. Unpublished study prepared by Ricerca, Inc. 133 p.

MRID: 42825830 Hatzenbeler, C. (1992) An Anaerobic Aquatic Soil Metabolism Study with (Ph-(carbon 14))-S-23031: Lab Project Number: 3444-89-0288-EF-001. Unpublished study prepared by Ricerca, Inc. 154 p.

Guideline: 163-1 Leach/adsorp/desorption

------------------------------------------------------------------------------------- MRID: 42169845 Waller, R. (1991) Preliminary Adsorption and Desorptio n of IMCA to Soils: Lab Project Number: 91-0089. Unpublished study prepared by Ricerca, Inc. 76 p.

MRID: 42169846 Waller, R. (1991) Adsorption and Desorption of AFCA to Soils: Lab Project Number: 91-0096. Unpublished study prepared by Ricerca, Inc. 118 p.

MRID: 42169847 Korsch, B. (1991) An Unag ed Soil Column Leaching St udy with ?PH-?carbon 14||-V- 23031: Lab Project Number: 89-0383. Unpublished study prepared by Ricerca, Inc. 169 p.



### 43 of 67MRID: 42169848 Korsch, B. (1991) An Unag ed Soil Column Leaching Study with ?THP-?carbon 14||-V-2 3031: Lab Project Number: 89-0383. Unpublished study prepared by Ricerca, Inc. 170 p.

MRID: 42825831 Rose, A. (1993) Response to EPA Review DP Barcode: D174435, 176257, PC Code No. 128724, "An Unaged Soil Column Leaching Study with (PH-(car bon 14))-V-23031", "An Unaged Soil Column Leaching Study with (THP- (carbon 14))-V-23031" and "Adsorption and Desorption of AFCA to Soils": Lab Project Number: 93-RES-012. Unpublished study prepared by Valent USA Corp. 43 p.

MRID: 42825832 Lee, D. (1992) An Aged Soil Column Leaching Study with (THP-(carbon 14))-V-2 3031: Lab Project Number: 3422-91-0215-EF-001. Unpublished study prepared by Ricerca, Inc. 158 p.

MRID: 42825833 Archer, G. (1992) An Aged Soil Column Leaching Study with (PH-(carbon 14))-V-23031: Lab Project Number: 3422-89-0252-EF-001. Unpublished study prepared by Ricerca, Inc. 155 p.

MRID: 42986501 Lee, D. (1993) An Aged Soil Column Leaching Study with (PH-(car bon 14))-V-23031: Re vised Report-MRID 42825833: Lab Project Number: 3422-89-0252-EF-002. Unpublished study prepared by Ricerca, Inc. 162 p.

MRID: 42986502 Lee, D. (1993) An Aged Soil Column Leaching Study with (THP-(carbon 14))-V-2 3031: Revised Report-MRID 42825832: Lab Project Number: 3422-91-0215-EF-002: 3422-91-0215.F-000: Unpublished study prepared by Ricerca, Inc. 165 p.

Guideline: 164-1 Terrestrial field dissipation

------------------------------------------------------------------------------------- MRID: 42825834 Cassidy, P.; Dillon, K. (1992) Stability of V-23031 in IMCA in Mississippi Soil (Data Through Five Months): Lab Project Number: 3970-91-0200: 3970-91-0200-CR-001: V-23031. Unpublished study prepared by Ricerca, Inc. 54

p.

MRID: 42825836 Kurtz, A. (1992) Field Dissipation Study with V-23031 Herbicide on Bare Ground in Mississippi: Lab Project Number: 3949-91-0182. Unpublished study prepared by Valent USA Corp. and Ricerca, Inc. 291 p.

MRID: 42825837 Kurtz, A. (1992) Field Dissipation Study with V-23031 Herbicide on Bare Ground in Iowa: Lab Project Number: 3949-91-0183. Unpublished study prepared by Valent USA Corp and Ricerca, Inc. 353 p.

MRID: 42825838 Cassidy, P.; Dillon, K. (1992) Stability of V-23031 and IMCA in Iowa Soil (Data Through Five Months): Lab Project Number: 3971-91-0201. Unpublished study prepared by Ricerca, Inc. 53 p.

MRID: 42825839 Kurtz, A. (1993) Soil Dissipation of (carbon 14)-V-23031 un der Field Conditions in North Carolina: Lab Project Number: 10724: 599: 5025-91-0282-EF-001. Unpublished study prepared by PTRL East, Inc. and Ricerca, Inc. 315 p.

MRID: 43063601 Kurtz, A. (1993) Soil Dissipation of (carbon 14)-V-23031 Under Field Conditions in Kentucky: Lab Project Number: 10809: 600: 5025-93-0444-EF-001. Unpublished study prepared by PTRL-East, Inc. and Ricerca, Inc. 267 p.



### 44 of 67MRID: 43275101 Nambu, K.; Radcliffe, M.; Rose, A. et al. (1994) Resp onse to EFGWB Review of Studies Submitted to Support EPA Guideline 164-1,DP Barcode D194610, 194615, 197255, 198102; PL Code No. 128724; Reg./File No. 020793, 020796; MRID Nos. 42825836, 42825837, 42825839, 43063601: Flumiclorac Pentyl Technical: Lab Project Number: 94-RES-004. Unpublished study prepared by Valent U.S.A. Corp. 57 p.

MRID: 43275102 Rose, K. (1994) A Soil Aging Study with (PH-(carbon 14))-V-23031 (Supplementary Study): Lab Project Number: 5008-91-0274-EF-001. Unpublished study prepared by Ricerca, Inc. 96 p.

MRID: 46563601 Kowalsky, J. (2005) Terrestrial Field Soil Dissipation of Fl umiclorac Pentyl Ester (Resource Herbicide) on Bare Soil in California. Project Number: V/27334, 200500065. Unpublished study prepared by Valent U.S.A. Corporation. 202 p.

Guideline: 165-1 Confined rotational crop

------------------------------------------------------------------------------------- MRID: 42825840 Korsch, B.; Doran, T. (1992) A Confined Crop Rotation Study with (carbon 14)-V-23031: Lab Project Number: 3363-89-0204-EF-001. Unpublished study prepared by Ricerca, Inc. 136 p.

MRID: 42825841 Korsch, B.; Doran, T. (1993) A Confined Crop Rotation Study with (carbon 14)-V-23031: Lab Project Number: 3363-91-0245-EF-001. Unpublished study prepared by Ricerca, Inc. 308 p.

MRID: 42825842 Hashimoto, S. (1993) Crop Phytotoxicity Study with Soil Applied S-23031 and Its Metabolites: Lab Project Number: SAG-30-0008. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 14 p.

MRID: 43002301 Korsch, B.; Doran, T. (1993) A Confined Crop Rotation Study with (carbon 14)-V-23031: Lab Project Number: 3363/91/0245/EF/002: 14C/V/23031. Unpublished study prepared by Ricerca, Inc. 374 p.

MRID: 43283001 Radcliffe, M.; Rose, A. (1994) Response to CBTS Review of Residue Data Submitted to Support the Tolerances of Flumiclorac Pentyl Ester, MRID Nos. 428258-40 through-50, 428839-07, 430023-01, CBTS Nos. 12902, 12655- 12647 (sic): Lab Proj. No. VP/94/RES/05. Unpublished study prepared by Valent U.S.A. Corp. 21 p.

Guideline: 165-4 Bioaccumulation in fish

------------------------------------------------------------------------------------- MRID: 42825812 Ohshima, M.; Mikami, N. (1993) Charact erization of (carbon 14) Residues in Bluegill Sunfish Treat ed with ((carbon 14)-PH)-S-23031: Lab Project Number: ACC90001-C: SAM-20-0031. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 127 p.

MRID: 42825813 Ohshima, M.; Mikami, N. (1993) Charact erization of (carbon 14) Residues in Bluegill Sunfish Treat ed with ((carbon 14)-PH)-S-23031: Lab Project Number: ACC90001-D: SAM-20-0032. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 147 p.



### 9.3. Submitted Effects Studies

Guideline: 71-1 Avian Single Dose Oral Toxicity



### 45 of 67------------------------------------------------------------------------------------- MRID: 42169802 Llyod, D.; Hoxter, H.; Jaber, M. (1990) V-23031: Acute Oral Toxicity Study with the Bobwhite: Lab Project Number: 263-105. Unpublished study prepared by Wildlife International, Ltd. 21 p.

Guideline: 71-2 Avian Dietary Toxicity

------------------------------------------------------------------------------------- MRID: 42169803 Driscoll, C.; Foster, J.; Hoxter, K. (1991) V-23031: A Di etary LC50 Study with the Northern Bobwhite: Revised: Lab Project Number: 263-103. Unpublished study prepared by Wildlife International, Ltd. 36 p.

MRID: 42169804 Driscoll, C.; Foster, J.; Hoxt er, K.; et al. (1991) V-23031: A Dietary LC50 Study with the Mallard: Revised: Lab Project Number: 263-104. Unpublished study prepared by Wildlife International, Ltd. 36 p.

Guideline: 71-4 Avian Reproduction

------------------------------------------------------------------------------------- MRID: 42825804 Beavers, J.; Foster, J.; Grimes, J.; et al. (1992) V-23031: A Pilot Reproduction Study with the Northern Bobwhite (Colinus virginianus): Lab Project Number: 263-116. Unpublished study prepared by Wildlife International Ltd. 72

p.

MRID: 42825805 Beavers, J.; Sipler, O.; Smith, G.; et al. (1992) V-23031: A One-Generation Reproduction Study with the Northern Bobwhite (Colinus virginianus): Lab Project Number: 263-123. Unpublished study prepared by Wildlife International Ltd. 163 p.

MRID: 42825806 Beavers, J.; Sipler, O.; Smith, G.; et al. (1992) V-23031: A One-Generation Reproduction Study with the Mallard (Anas platyrhynchos): Lab Project Number: 263-124. Unpublished study prepared by Wildlife International Ltd. 161 p.

MRID: 42825807 Beavers, J.; Foster, J.; Grimes, J.; et al. (1992) V-23031: A Pilot Reproduction Study with the Mallard (Anas platyrhynchos): Lab Project Number: 263-117. Unpublished study prepared by Wildlife International Ltd. 72 p.

Guideline: 72-1 Acut e Toxicity to Freshwater Fish

------------------------------------------------------------------------------------- MRID: 42169805 Takimoto, Y. (1991) Justification of the Use of HCO-40 as a Co-Solvent in Aquatic Toxicity Tests: Lab Project Number: 91-031-04. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 6 p.

MRID: 42169806 Takimoto, Y.; Hahino, S.; Saito, S. (1989) The Acute Toxi city of S-23031 to Rainbow Trout (Salmo gairdneri): Lab Project Number: FTX-89002. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 30 p.

MRID: 42169807 Takimoto, Y.; Hagino, S.; Saito, S. (1989) The Acute Toxi city of S-23031 to Bluegill (Lepomis macrochirus): Lab Project Number: FTX-89005. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 30 p.

Guideline: 72-2 Acute To xicity to Freshwater Invertebrates

------------------------------------------------------------------------------------- MRID: 42169808 Reed, D.; Peters, G. (1991) V-23031 Technical: A 48-Hour Flow-through Acute Toxicity Test with the Cladoceran (Daphnia Magna): Revised: Lab Project Number: 263A-108. Unpublished study prepared by Wildlife International, Ltd. 125 p.



### 46 of 67Guideline: 72-3 Acute Toxicity to Estuarine/Marine Organisms

------------------------------------------------------------------------------------- MRID: 42568601 Flanagan, J. (1992) Letter Sent to J. Miller, Dated Nov. 6, 1992: Providing Preliminary Oyster Toxicity Data on V23031 EC Formulation. Prepared by Valent U.S.A. Corp. 3 p.

MRID: 42825809 Bettencourt, M. (1992) V-23031 Technical--Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) Under Flow-Through Conditions: Lab Project Number: 92-5-4256. Unpublished study prepared by Springborn Lab, Inc. 61 p.

MRID: 42825810Bettencourt, M. (1993) V-23031 Technical--Acute Toxicity to Mysid Shrimp (Mysidopsis bahia) Under FlowThrough Conditions: Lab Project Number: 92-5-4272. Unpublished study prepared by Springborn Lab, Inc. 59 p.

MRID: 42825811 Dionne, E. (1992) V-23031 Technical--Acute Toxicity to Eastern Oyster (Crassostr ea virginica) Under FlowThrough Conditions: Lab Project Number: 12709-0192-6103-504: 92-7-4343. Unpublished study prepared by Springborn Lab, Inc. 62 p.

Guideline: 81-1 Acute oral toxicity in rats

------------------------------------------------------------------------------------- MRID: 42169811 Hiromori, T. (1990) Acute Oral Toxicity Study of S-23031 in Mice: Lab Project Number: 2005. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 21 p.

MRID: 42169812 Hiromori, T. (1989) Acute Oral Toxicity Study of S-23031 in Rats: Lab Project Number: 2000. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 21 p.

MRID: 42169813 Baldrick, P.; Healing, G. (1991) Acute Oral Toxicity to Rats of V-23031 0.83 EC: Lab Project Number: 901090D/VLT 1/AC. Unpublished study prepared by Huntingdon Research Centre Ltd. 20 p.

MRID: 43588904 Hoffman, G. (1994) Acute Oral Toxicity Study With Flumiclorac Pentyl-Lactofen 3.1 EC in Rats: Lab Project Number: 94-1001. Unpublished study prepared by Pharmaco LSR, Inc. 33 p.

MRID: 45553503 Bonnette, K. (2001) An Acute Oral Toxicity Study in Rats with V-10097: Lab Project Number: 3548.9. Unpublished study prepared by Springborn Laboratories, Inc. 43 p. {OPPTS 870.1100}

Guideline: 81-2 Acute dermal toxicity in rabbits or rats

------------------------------------------------------------------------------------- MRID: 42169814 Hiromori, T. (1989) Acute Dermal Toxicity Study of S-23031 in Rats: Lab Project Number: 2002. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 22 p.

MRID: 42169815 Baldrick, P.; Healing, G. (1991) Acute Dermal Toxicity to Rats of V-23031 0.83 EC: Lab Project Number: 901091D/VLT 2/AC. Unpublished study prepared by Huntingdon Research Centre Ltd. 17 p.

MRID: 43588905 Hoffman, G. (1994) Acute Dermal Toxicity Study With Flumiclorac Pentyl-Lactofen 3.1 EC in Rabbits: Lab Project Number: 94-1002. Unpublished study prepared by Pharmaco LSR, Inc. 24 p.



### 47 of 67MRID: 45553501 Bonnette, K. (2001) An Acute Dermal Toxicity Study in Rats with V-10097: Lab Project Number: 3548.10. Unpublished study prepared by Springborn Laboratories, Inc. 52 p. {OPPTS 870.1200}

Guideline: 81-3 Acute inhalation toxicity in rats

------------------------------------------------------------------------------------- MRID: 42169816 Kawaguchi, S. (1990) Acute Inhalation Toxicity Study of S-23031 in Rats: Lab Project Number: 2036. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 44 p.

MRID: 42169817 Jackson, G.; Hardy, C.; Morrow, J.; et al. (1991) V-23031 0.83 EC Acute Inhalation Toxicity in Rats: Lab Project Number: VLT 12/91347. Unpublished study prepared by Huntingdon Research Centre Ltd. 101 p.

MRID: 42394401 Flanagan, J. (1992) Letter Sent to J. Miller dated June 29 , 1992: ?Concerning effects observed in an acute inhalation study conducted with V-23031 Herbicide|. Prepared by Valent U.S.A., Corp. 3 p.

MRID: 42825814 Jackson, G.; Hardy, C.; Morrow, J.; et al. (1992) V-23031 0.83 EC, Acute Inhalation Study in Rats, Four-Hour Exposure, Determination of the No-Effect Level: Supplemental: Lab Project Number: VLT 14/920395. Unpublished study prepared by Huntingdon Research Centre Ltd. 90 p.

MRID: 43588906 Hoffman, G. (1994) An Acute (4-Hour) Inhalation Toxicity Study of Flumiclorac Pentyl-Lactofen 3.1 EC in the Rat Via Nose-Only Exposure: Lab Project Number: 94-5190. Unpublished study prepared by Pharmaco LSR, Inc. 151

p.

MRID: 45553502 Bonnette, K. (2001) An Acute Nose-Only Inhalation Toxic ity Study in Rats with V-10097: Lab Project Number: 3548.11. Unpublished study prepared by Springborn Laboratories, Inc. 70 p. {OPPTS 870.1300}

Guideline: 81-4 Primary eye irritation in rabbits

------------------------------------------------------------------------------------- MRID: 42169818 Yamada, H. (1989) Primary Eye Skin Irritation Tests with S-23031 in Rabbits: Lab Project Number: 1693. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 21 p.

MRID: 42169819 Liggett, M.; McRae, L. (1991) Eye Irritation to the Rabbit of V-23031 0.83 EC: Lab Project Number: 901150D/VLT 4/SE. Un- published study prepared by Huntingdon Research Centre Ltd. 12 p.

MRID: 43588907 Hoffman, G. (1994) Primary Eye Irritation Study With Flumiclorac Pentyl-Lactofen 3.1 EC in Rabbits: Lab Project Number: 94-1003. Unpublished study prepared by Pharmaco LSR, Inc. 29 p.

MRID: 44298902 Blaszcak, D. (1997) Prim ary Eye Irritation Study with Resource 80 WP in Rabbits: Lab Proj ect Number: 96-1512: 9700125. Unpublished study prepared by Huntingdon Life Sciences. 28 p.

MRID: 45553506 Bonnette, K. (2001) A Primary Eye Irritation Study in Rabbits with V-10097: Lab Project Number: 3548.12. Unpublished study prepared by Springborn Laboratories, Inc. 42 p. {OPPTS 870.2400}

Guideline: 81-5 Primary dermal irritation



### 48 of 67------------------------------------------------------------------------------------- MRID: 42169818 Yamada, H. (1989) Primary Eye Skin Irritation Tests with S-23031 in Rabbits: Lab Project Number: 1693. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 21 p.

MRID: 42169820 Liggett, M.; McRae, L. (1991) Skin Irritation to th e Rabbit of V-23031 0.83 EC: Lab Project Number: 901125D/VLT 3/SE. Un- published study prepared by Huntingdon Research Centre. 11 p.

MRID: 42883901 Nakanishi, T. (1992) Primary Skin Irritation Test with S- 23031 in Rabbits: Lab Project Number: 2648. Unpublished study prepared by Environmental Health Science Lab. 13 p.

MRID: 43588908 Hoffman, G. (1994) Primary Dermal Irritation Study With Flumiclorac Pentyl-Lactofen 3.1 EC in Rabbits: Lab Project Number: 94-1004. Unpublished study prepared by Pharmaco LSR, Inc. 22 p.

MRID: 44298903 Blaszcak, D. (1997) Primary Dermal Irr itation Study with Resource 80 WP in Rabbits : Lab Project Number: 96- 1511: 9700134. Unpublished study prepared by Huntingdon Life Sciences. 22 p.

MRID: 45553507 Bonnette, K. (2001) A Primary Skin Irritation Study in Rabbits with V-10097: Lab Project Number: 3548.13. Unpublished study prepared by Springborn Laboratories, Inc. 45 p. {OPPTS 870.2500}

Guideline: 81-6 Dermal sensitization

------------------------------------------------------------------------------------- MRID: 42169821 Yamada, H. (1989) Skin Sensitization Test with S-23031 in Guinea Pigs (Buehler Method): Lab Project Number: 1880. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 18 p.

MRID: 42169822 Nakanishi, T. (1989) Skin Sensitization Test with S-23031 in Guinea Pigs (Maximization Method): Lab Project Number: 1698. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 19 p.

MRID: 42169823 Parcell, B.; Healing, G. (1991) Skin Sensitization in the Guinea Pig of V-23031 0.83EC: Lab Project Number: 91722D/VLT 13/SS. Unpublished study prepared by Huntingdon Research Center Ltd. 24 p.

MRID: 42169824 Parcell, B.; Denton, S. (1991) Skin Sensitization in Guinea- Pig of V-23031 0.83 EC: Lab Project Number: 90116D/VLT 5/SS. Unpublished study prepared by Huntingdon Research Centre Ltd. 21 p.

MRID: 42169825 Piccirillo, V. (1991) Dermal Sensitization Potential of V-23031 Technical and V-23031 0.83 EC: Lab Project Number: 91-031-07. Unpublished study prepared by NPC, Inc. 5 p.

MRID: 42883902 Nakanishi, T. (1992) Skin Sensitization Test of S-23031 in Guinea Pigs: Lab Project Number: 2649. Unpublished study prepared by Environmental Health Science Lab. 17 p.

MRID: 43588909 Hoffman, G. (1994) Closed-Patch Rep eated Insult Dermal Sensitization Study With Flumiclorac Pentyl-Lactofen 3.1 EC in Guinea Pigs (Buehler Method): Lab Project Numbers: 94-1005: VP-10930. Unpublished study prepared by Pharmaco LSR, Inc. 107 p.



### 49 of 67MRID: 45553504 Bonnette, K. (2001) A Dermal Sensitization Study in Gu inea Pigs with V-10097 Modified Buehler Method: Lab Project Number: 3548.14. Unpublished study prepared by Springborn Laboratories, Inc. 64 p. {OPPTS 870.2600}

Guideline: 82-1 Subchronic Oral Toxicity: 90-Day Study

------------------------------------------------------------------------------------- MRID: 42169826 Yoshida, Y. (1990) Three Month Subacute Toxicity Study of S-23031 by Dietary Administration in Rats: Lab Project Number: 1632. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 443 p.

MRID: 42169827 Nakano, M. (1991) Three-Month Oral Toxicity Study of S-23031 in Dogs: Lab Project Number: 1823. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 159 p.

MRID: 42310801 Yoshida, Y. (1990) Addendum to Three Month Subacute Toxicity Study of S-23031 by Dietary Administration in Rats: Abbreviations, Historical Controls, Statistical An alyses: Lab Project Number: 1632. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 9 p.

MRID: 42310802 Nakano, M. (1991) Addendum to Three-Month Oral Toxicity Study of S-23031 in Dogs: Measurements, Statistical Methods, Historical Controls: Lab Project Number: 1823. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 8 p.

MRID: 42883903 Tamano, S. (1990) 13-Week Subchronic Oral Toxicity Study of S-23031 Pure in Rats: Lab Project Number: 8803. Unpublished study prepared by Sumitomo Chemical Company, Ltd. 583 p.

MRID: 42883904 Yamada, H. (1990) Three Month Subacute Toxicity Study of S-23031 by Dietary Administration in Mice: Lab Project Number: 1650. Unpublished study prepared by Sumitomo Chemical Company, Ltd. 157 p.

Guideline: 82-2 21-day dermal-rabbit/rat

------------------------------------------------------------------------------------- MRID: 42825815 Osheroff, M. (1991) 21-Day Dermal Toxicity Study in Rats with S-23031: Lab Project Number: 343-229. Unpublished study prepared by Hazleton Labs America, Inc. 216 p.

MRID: 42825816 Moore, M. (1992) 21-Day Dermal Toxicity Study in Rats with V-23031 (0.83EC): Lab Project Number: 2615-100. Unpublished study prepared by Hazleton Washington, Inc. 273 p.

MRID: 43158801 Osheroff, M. (1991) 21-Day Dermal Toxicity Study in Rats with S-23031, MRID No. 42825815, Clinical Observation: Lab Project Number: 343-229. Unpublished study prepared by Hazleton Laboratories America, Inc. 101 p.

MRID: 43171801 Moore, M. (1992) 21-Day Dermal Toxicity Study in Rats with V-23031 (0.83 EC): Supplement: Lab Project Number: 2615-100. Unpublished study prepared by Hazleton Washington, Inc. 9 p.

Guideline: 83-1 Chronic Toxicity

------------------------------------------------------------------------------------- MRID: 42825817 Dalgard, D. (1992) Chronic Toxicity Study in Dogs with S-23031: Lab Project Number: 343-233. Unpublished study prepared by Hazleton Washington, Inc. 411 p.



### 50 of 67MRID: 42883906 Adachi, H. (1992) Combined Chronic Toxicity and Oncogenicity Study of V-23031 by Dietary Administration in Rats: Lab Project Number: 1716. Unpublished study prepared by Environmental Health Science Lab. 1716 p.

MRID: 44299101 Goldenthal, E. (1997) Evaluation of (inert ingredient) in a One Year Chronic Dietary Toxicity Study in Dogs: Lab Project Number: 647-003. Unpublished study prepared by MPI Research. 186 p.

Guideline: 83-2 Oncogenicity

------------------------------------------------------------------------------------- MRID: 42883905 Adachi, H. (1992) Oncogenicity Study of S-23031 by Dietary Administration in Mice: Lab Project Number: 1842. Unpublished study prepared by Sumitomo Chemical Company, Ltd. 3771 p.

MRID: 42883906 Adachi, H. (1992) Combined Chronic Toxicity and Oncogenicity Study of V-23031 by Dietary Administration in Rats: Lab Project Number: 1716. Unpublished study prepared by Environmental Health Science Lab. 1716 p.

Guideline: 83-3 Teratogenicity -- 2 Species

------------------------------------------------------------------------------------- MRID: 42169828 Morseth, S. (1990) 5-Day Oral Toxicity Study in Fe male Rabbits with S-23031: Lab Project Number: HLA 343- 219. Unpublished study prepared by Hazleton Labs America, Inc. 71 p.

MRID: 42169829 Morseth, S. (1990) Range-Finding Rabbit Teratology Study with S-23031: Lab Project Number: HLA 343-220. Unpublished study prepared by Hazleton Labs America, Inc. 137 p.

MRID: 42169830 Lemen, J. (1991) Rabbit Teratology Study with S-23031: Lab Project Number: HLA 343-221. Unpublished study prepared by Hazleton Labs America, Inc. 231 p.

MRID: 42169831 Morseth, S. (1990) Dose-Finging Study for Teratology Study in Rats with S-23031: Lab Project Number: HLA 343- 222. Unpub- published study prepared by Hazleton Labs America, Inc. 193 p.

MRID: 42169832 Lemen, J. (1991) Rat Teratology Study with S-23031: Lab Project Number: HLA 343-223. Unpublished study prepared by Hazleton Labs America, Inc. 251 p.

MRID: 42169833 Nishimura, K. (1991) A Journal Artic le Entitled "A Micro- dissection Meth od for Detecting Thoracic Visceral Malformations in Mouse and Rat Fetuses": Lab Project Number: 91-031-03. Unpublished study prepared by Dainippon Pharmaceutical Co., Ltd. , Research Lab. 28 p.

Guideline: 83-4 2-generation repro.-rat

------------------------------------------------------------------------------------- MRID: 42169834 Nemec, M. (1990) A Dietary Dose Range-Finding Reproductive Toxicity Study of S-23031 in Rats: Lab Project Number: WIL-118007. Unpublished study prepared by WIL Research Labs., Inc. 513 p.

MRID: 42169835Nemec, M. (1991) A Dietary Two-generation Reproduction Study of S-23031 in Rats: Lab Project Number: WIL118008. Unpublished study prepared by WIL Research Labs., Inc. 2509 p.



### 51 of 67Guideline: 83-5 Dietary: Combined Chronic To xicity/Oncogenicity Studies

------------------------------------------------------------------------------------- MRID: 42187406 Adachi, H. (1990) Combined Chronic Toxicity and Oncogenicity Study of S-23031 by Dietary Administration in Rats (52-Week Interim Report): Lab Project Number: 1716. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 1912 p.

Guideline: 84-2 Intreraction with Gonadal DNA

------------------------------------------------------------------------------------- MRID: 42169836 Kogiso, S. (1989) Reverse Mutation Test of S-23031 in Salmonella typhimurium and Escherichia coli: Lab Project Number: 1677. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 21 p.

MRID: 42169837 Hara, M. (1990) Micronucleus Test of S-23031 in ICR Mice: Lab Project Number: 2031. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 23 p.

MRID: 42169838 Kogiso, S. (1989) In vitro Chromosomal Aberration Test of S-23031 in Chinese Hamster Ovary Cells (CHO-K1): Lab Project Number: 1875. Unpublished study prepared by Sumitomo Chemical Co. 29 p.

MRID: 42169839 Kogiso, S. (1989) In vitro Unscheduled DNA Synthesis (UDS) Assay of S-23031 in Rat Hepatocytes: Lab Project Number: 1929. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 53 p.

MRID: 42684942 Hara, M.; Kogiso, S. (1988) Micronucleus Test of S-23031 and S-53482: Lab Project Nos. 1168; 1169. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 8 p.

MRID: 42825818 Kogiso, S. (1992) Reverse Mutation Test of S-23031 in Salmonella typhimurium and Escherichia coli: Report Amendment Number One: Lab Project Number: 1677. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 24 p.

MRID: 42825819 Kogiso, S. (1992) In Vitro Chromosomal Aberration Test of S-23031 in Chinese Hamster Ovary Cells (CHO-K1): Revised Reeport (sic) Number One: Lab Project Number: 1875. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 31 p.

Guideline: 85-1 General metabolism

------------------------------------------------------------------------------------- MRID: 42169840 Isobe, N. (1991) Metabolism of S-23031 in Rats: Re vised: Amended Report: Lab Project Number: 1918. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 238 p.

MRID: 42825820 Radcliffe, M. (1993) Metabolism of S-23031 in Rats Revised: Revised Reeport (sic) Number One: Lab Project Number: 93-RES-011. Unpublished study prepared by Valent USA Corp, Inc. 5 p.

MRID: 42825821 Matsunaga, H. (1993) Bile Excretion Study of (Phenyl-(carbon 14))S-23031 in Male Rats: Lab Project Number: 2661. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 85 p.

MRID: 42825822 Matsunaga, H. (1993) Metabolism of S-23031 in Rats: (Tetrahydrophthaloyl-1,2-(carbon 14))S-23031: Lab Project Number: 2474. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 289 p.



### 52 of 67

### 53 of 67 MRID: 42825823 Matsunaga, H. (1993) Purification and Identification of Fecal and Urinary Metabolism of S-23031 in Rats: Lab Project Number: X0003. Unpublished study prepared by Sumitomo Chemical Co, Ltd. 66 p.

Guideline: 122-1 Seed Germina tion/Seedline Emergence and Vegetable Vigor

------------------------------------------------------------------------------------- MRID: 43104701 Hashimoto, S. (1994) Seed Germination Study with Metabolites of S-23031: Lab Project Number: 930260-M. Unpublished study pre- pared by Sumitomo Chemical Co., Ltd. 7 p.

MRID: 43258001 Hoberg, J. (1994) IMCA-Determination of Effects on Seedling Emergence of Ten Plant Species: Lab Project Number: 94-2-5175: VP-10812. Unpublished study prepared by Springborn Lab., Inc. 77 p.

Guideline: 122-2 Aquatic plant growth

------------------------------------------------------------------------------------- MRID: 43240801 Hoberg, J. (1994) IMCA-Acute Toxicity to the Freshwater Green Alga (Sel enastrum capricornut um): Lab Project Number: VP-10814: 94-4-5221: 12709.0294.6134.430. Unpublished study prepared by Springborn Labs., Inc. 58

p.

MRID: 43251201 Hoberg, J. (1994) IMCA-Acute Toxicity to Duckweed, Lemna gibba: Lab Project Number: VP-10819: 94-5-5255: 12709.0294.6135.410. Unpublished study prepared by Springborn Labs, Inc. 67 p.

Guideline: 123-1 Seed germination/seedling emergence and vegitative vigor

------------------------------------------------------------------------------------- MRID: 43347401 Chetram, R. (1994) Tier 2 Vegetative Vigor Nontarget Phytotoxicity Study Using Resource Herbicide: Lab Project Number: 94397: VP-11058. Unpublished study prepared by Pan-Agricultural Labs, Inc. 247 p.

Guideline: 141-1 Honey bee acute contact

------------------------------------------------------------------------------------- MRID: 42169841 Thompson, M.; Hoxter, K.; Jaber, M. (1990) V-23031: An Acute Contact Toxicity Study with the Honey Bee: Lab Project Number: 263-114. Unpublished study prepared by Wildlife International Ltd. 17 p.Appendix A: Summary of Toxicity DataTable D1. Summary of Submitted Aquatic Toxicity Data for Flumiclorac-pentyl.Reported Solubility of flumiclorac-pentyl is 0.189 mg/LStudyTypeTest Species(GenusSpecies)/ Flowthrough/Static% a.i.Toxicity Endpoint(Measured/Nominal)EffectMRID(Year)Classificationor SourceCommentsFreshwater VertebratesAcute850.107572-3Bluegill Sunfish(Lepomismacrochirus)/Flow-ThroughTGAI94.796-hr LC50= 17.4 mg/L(measured)1(16.5 mg ai/L)LOAEC = 13 mg/LNOAEC = 7.8 mg/L96-hr LC50> 0.189 mg/L2Mortality42169807(1989)SupplementalDER 4/29/92Test solution appearance not reported, and basedon water solubility and other studies, precipitatemay have been present. Water was notcentrifuged or filtered before measuringconcentrations. DMF:HCO-40 (1:1) solvent waspresent at maximum concentrations of 3200 ppm.True exposure concentrations cannot bedetermined. Sublethal effects included abnormalrespiration, loss of equilibrium and lethargy. Nosublethal effects were observed at 7.8 mg/L andbelow. Measured concentrations ranged from 66-78% of nominal and mortality occurred at 13mg/L. No replicates.54 of 67StudyTypeTest Species(GenusSpecies)/ Flowthrough/Static% a.i.Toxicity Endpoint(Measured/Nominal)EffectMRID(Year)Classificationor SourceCommentsAcute850.107572-3Rainbow Trout(Salmo gairneri)/Flow-ThroughTGAI94.796-hr LC50= 1.1 mg/L(measured)1(1.0 mg ai/L)LOAEC = 0.87 mg/LNOAEC = 0.51 mg/L96-hr LC50> 0.189 mg/L2Mortality42169806(1989)SupplementalDER 4/29/92Test solution appearance not reported, and basedon water solubility and other studies, precipitatemay have been present. Water was notcentrifuged or filtered before measuringconcentrations. DMF:HCO-40 (1:1) solvent waspresent at maximum concentrations of 560 ppm.True exposure concentrations cannot bedetermined. Sublethal effects included swimmingin surface water, on-bottom orientation, loss ofequilibrium and lethargy. No sublethal effectswere observed at 0.51 mg/L. Measuredconcentrations ranged from 87 - 94% of nominaland mortality occurred at 0.87 mg/L and above.No replicates.Estuarine/Marine VertebratesAcute850.107572-3SheepsheadMinnow(Cyprinodonvariegatus)/Flow-ThroughTGAI94.696-hr LC50> 24 mg ai/L(measured)1LOAEC > 24 mg ai/LNOAEC = 24 mg ai/L96-hr LC50> 0.189 mg/L2Mortality42825809(1992)SupplementalDER 2/10/94Precipitate was observed in all test treatments.Water was not centrifuged or filtered beforemeasuring concentrations. DMF:HCO-40 (1:1)solvent was present at maximum concentrations of4mL DMF:HCO-40/L. True exposureconcentrations cannot be determined. Nosublethal effects were observed in any treatmentgroup. One mortality (5%) in the solvent controland highest treatment group. Solvent Controlconcentration probably at maximum tolerableconcentration. Measuredconcentrations averaged95% of nominal. Two replicates.55 of 67StudyTypeTest Species(GenusSpecies)/ Flowthrough/Static% a.i.Toxicity Endpoint(Measured/Nominal)EffectMRID(Year)Classificationor SourceCommentsFreshwater InvertebratesAcute850.101072-3Waterflea(Daphniamagna)/Flow-ThroughTGAI94.648-hr EC50> 38.0 mg/L(measured)1(35.9 mg ai/L)LOAEC = 3.98 mg/LNOAEC = 1.88 mg/L48-hr EC50> 0.189 mg/L2Mortality42169808(1991)SupplementalDER 5/26/92Precipitate was observed in all test treatments.Water was not centrifuged or filtered beforemeasuring concentrations. DMF:HCO-40 (1:1)solvent was present at maximum concentrations of4mL DMF:HCO-40/L. True exposureconcentrations cannot be determined. Sublethaleffects included lethargy, and white precipitateclinging to daphnids in high treatment group.Measured concentrations ranged 75 to 102% ofnominal. Two replicates.Estuarine/Marine InvertebratesAcute850.102572-3Eastern Oyster(Crassostreavirginica)/Flow ThroughTGAI94.696-hr EC50> 1.8 mg ai/L(measured)196-hr EC50> 0.189 mg/L2ShellGrowth42825811(1992)InvalidDER 2/10/94The test solution in the two highest testconcentrations was cloudy. Solvent concentration(DMF) was 0.5 mL DMF/L.Test concentrationsdecreased substantially during study and averaged31% of nominal. DO levels also dropped duringstudy and was 28 to 104% of saturation. Shelldeposition in controls was less than minimum 2mm.56 of 67StudyTypeTest Species(GenusSpecies)/ Flowthrough/Static% a.i.Toxicity Endpoint(Measured/Nominal)EffectMRID(Year)Classificationor SourceCommentsAcute850.103572-3Mysid Shrimp(Mysidopsisbahia)/Flow Through<24-hr oldTGAI94.696-hr LC50= 0.56 mg ai/L(measured)NOAEC = 0.11 mg ai/LMortality42825810(1993)AcceptableDER 1/28/94No undissolved test material was observed in thediluter system or any test solutions. SolventConcentration was 0.5mL DMF/L. Sublethaleffects were loss of equilibrium, erratic swimmingand darkened pigmentation. Measured testconcentrations ranged from 28 – 53% of nominal.Low measured test concentrations believed to bedue to degradation of flumiclorac-pentyl. Tworeplicates.Aquatic Vascular and Nonvascular PlantsAcute850.4400122-2Duckweed(Lemna gibba)/Static-renewalIMCA398.0EC50> 0.035 mg IMCA/L(measured)Increase of 3.3% and 12.8%for frond number and dryweight, respectively, fortreatment compared tonegative controlGrowth43251201(1994)AcceptableDER10/24/94Study conducted for 14 days, and solutionsrenewed on days 3, 6, 9 and 12. Limit testconducted at nominal conc. of 0.032 mg IMCA/L.Acute850.5400122-2Green Algae(Selenastrumcapricornutum)IMCA398.0EC50> 0.035 mg IMCA/L(measured)Decrease of 4.1% in celldensity compared to negativecontrolGrowth43240800(1994)AcceptableDER10/24/94Study conducted for 120 hours. Limit testconducted at nominal conc. of 0.032 mg IMCA/L.Abbreviations: TGAI = technical gradeactive ingredient; conc.=concentration1Based on mean measured test concentrations, but due to presence of precipitate or lackof reported test solution, true test concentration not known.2LC or EC50greater than reported water solubility of 0.189 mg/L flumiclorac-pentyl.3Due to rapid degradation of flumiclorac-pentyl and major degradate IMCA being mobile in soils and possibly bioactive, study conducted with IMCA. Sinceherbicide Resource is applied at 0.0806 lbai/A and degradate IMCA is 53% of parent, the maximum application rate for IMCA was0.046 lb ai/A. When thisamount if applied to 6 inches of water a concentration of 0.032 ppm ai was calculated.57 of 67Table D2. Summary of terrestrial toxicitydata submitted for flumiclorac-pentyl.Study TypeTest SpeciesTGAI orTEPToxicity Endpoint(95% C.I.)(Measured/Nominal)/SlopeEffectMRID (Year)Classification,DER date orsourceComments870.11Acute OralRatTGAILD50> 5000 mg/kgMortality42169812U.S. EPA 2005d870.11Acute OralRatTEPLD50= 4100 mg/kg maleLD50= 3200 mg/kgfemaleLD50= 3600 mg/kg bothMortality42169813U.S. EPA 2005d870.3100Subchronic Oral(90 day oral)RatTGAINOAEL = > 1359/1574mg/kg/day (M/F)LOAEL= not identified42169823,42310801(1990)AcceptableU.S. EPA 2005d870.4300Chronic/Carcinog-enicity ToxicityRatTGAINOAEL = > 744.9/919.4 mg/kg/day (M/F)LOAEL = not identifiedNo evidence of carcinogenicity42883906(1992)AcceptableU.S. EPA 2005d870.4100bChronic ToxicityDogTGAINOAEL = 100 mg/kg/dayLOAEL = 1000 mg/kg/dayDecreased body weight gain in male,increased clottingtime, increased globulinlevels, increased alpha-2 fraction of theserum protein electrophoresis in females42825817(1992)AcceptableU.S. EPA 2005d870.3800Reproduction andFertility EffectsRatTGAINOAEL= 16/18 mg/kg/day (M/F)LOAEL=781/925 mg/kg/day (M/F)Increased kidney weight in males andfemales and nephropathy in males42169835(1991)AcceptableU.S. EPA 2005d58 of 67Study TypeTest SpeciesTGAI orTEPToxicity Endpoint(95% C.I.)(Measured/Nominal)/SlopeEffectMRID (Year)Classification,DER date orsourceCommentsAvian850.2100Acute OralBobwhite Quail(Colinusvirginianus)Age=16 wks.Bw= 170-186 gTGAI94.7LD50> 2250 mg/kg-bw(nominal) (2131 mgai/kg-bw)None observed42169802(1990)AcceptableDER 4/28/9210 birds (5 males/5 females) pertreatment. Necropsies not performed.Group weights taken rather thanindividual weights.850.2200Acute DietaryBobwhite Quail(Colinusvirginianus)Age = 10 daysTGAI94.78-day LC50> 5620mg/kg-diet (nominal)(5322 mg ai/kg-diet)NOAEC = 5620 mg/kgdietNone observed42169803(1991)Acceptable10 birds per treatment group.Measured concentration in freshlyprepared diets ranged from 83.4 to101% of nominal. Group weightsinstead of individual weights.Necropsies not conducted. Humidityless than recommended 30%,temperature was 39 ±3°C, which isgreater than recommended 35°C.850.2200Acute DietaryMallard Duck(Anasplatyrhynchos)Age = 10 dayTGAI94.78-day LC50> 5620mg/kg-diet (nominal)(5322 mg ai/kg-diet)NOAEC = 5620 mg/kgdietNone observed42169804(1991)AcceptableDER 4/28/9210 birds per treatment group.Measured concentration in freshlyprepared diets ranged from 83.4 to101% of nominal. Group weightsinstead of individual weights.Necropsies not conducted.Temperature was 30 ±3°C, which islower than recommended 35°C.850.2300ReproductiveBobwhite Quail(Colinusvirginianus)Age = 32 wksTGAI94.61-generation NOAEC =439 mg ai/kg-diet(measured) (highest testconcentration tested)No mortality orreproductiveeffects attributedto treatment42825805(1992)AcceptableDER 2/4/9416 pens with one males and one female.Two mortalities in control and one intwo lowest groups, and believed to beincidental based on necropsies. Eggsstored at 13.8°C instead ofrecommended 16°C. Eggs were set at37.5°C and 56% humidity instead ofrecommended 39°C and 70%. Eighthours of light provided instead of sevenfor first seven weeks of study.59 of 67Study TypeTest SpeciesTGAI orTEPToxicity Endpoint(95% C.I.)(Measured/Nominal)/SlopeEffectMRID (Year)Classification,DER date orsourceCommentsReproductiveMallard Duck(Anasplatyrhynchos)Age = 17 wksTGAI94.71-generationNOAEC= 220 mg ai/kgdiet (measured)LOAEC = 432 mg ai/kgdietDecrease in egglaying andregressed ovariesand testes42825806(1992)AcceptableDER 1/19/9416 pens with one males and one female.One mortalities lowest groups, andbelieved to be incidental based onnecropsies. Eggs stored at 13.8°Cinstead of recommended 16°C. Eggswere set at 37.5°C and 56% humidityinstead of recommended 39°C and70%. Eight hours of light providedinstead of seven for first seven weeksof study. Withdrawal period notincluded which is recommended wheneffects are observed.Terrestrial Invertebrates850.3020Acute ContactHoney Bee(Apis melliferaL.)TGAI94.7LD50> 106μg/beeNo treatmentrelated mortality42169841(1990)AcceptableDER 4/14/92Bees were exposed to direct applicationof flumiclorac-pentyl in combinationwith acetone. Incidental mortalityranged from 4-12% in controls and 8-14% in treatment groups.Terrestrial Plants850.4100122-1SeedlingEmergenceCabbage, corncucumber,lettuce, oat,onion,perennialryegrass,soybean,tomato, turnipIMCA198.0EC25> 0.046 lb ai/ANOAEC < 0.046 lb ai/AGrowth43258001(1994)AcceptableDER 10/24/9414-day study. Limit test conducted atnominal conc. of 0.032 mg IMCA/L.No treatment mortalities ormorphological abnormalities observedin any test species. Statisticallysignificant reduction was observed inshoot lengths of onion and oatcompared to negative control.Reduction was≤15%.60 of 6761 of 67Study TypeTest SpeciesTGAI orTEPToxicity Endpoint(95% C.I.)(Measured/Nominal)/SlopeEffectMRID (Year)Classification,DER date orsourceComments850.4250123-1Vegetative VigorCorn, oat,onion,perennialryegrass,soybean,tomato,cucumber,lettuce, radishand cabbageTEP10.6EC25= 0.0027 lb ai/A –lettuce(dicot, dry weight)EC25= 0.0410 lb ai/A –onion (monocot,dryweight and height )NOEC = 0.00031 lb ai/Atomato(dicot,phytotoxicity)NOEC = 0.040 lb ai/AOnionGrowth43347401(1994)AcceptableDER 10/24/94EPA toxanal computer program toprovide EC50values, and slope wasused to calculate EC25values. NOECvalues reported based on study authorsstatement since these values based onphytotoxic symptoms.1Due to rapid degradation of flumiclorac-pentyl and major degradate IMCA being mobile in soils and possibly bioactive, study conducted with IMCA. Sinceherbicide Resource is applied at 0.0806 lbai/A and degradate IMCA is 53% of parent, the maximum application rate for IMCA was0.046 lb ai/A. When thisamount if applied to 6 inches of water a concentration of 0.032 ppm ai was calculated.

### 62 of 67 

## Appendix B. Memorandum: Request for Phototoxicity Study Protocol for Light-Dependent Peroxidizing Herbicides

UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM

SUBJECT: Request for Photot oxicity Study Protocol for Li ght-Dependent Peroxidizing

Herbicides

DATE: March 7, 2001

TO: Elizabeth Leovey, Acting Director

Environmental Fate and Effects Division Office of Pesticide Programs

FROM: Norman B. Birchfield, Ph.D. Thomas M. Steeger, Ph.D. Brian Montague Aquatic Biology Tech Team

The light-dependent peroxidizing herbicides (L DPHs) are a growing class of weed control chemicals (see partial listing attached). Th ey act in plants by inhibiting the enzyme protoporphyrinogen oxidase (protox), which is the last common enzyme in the heme and chlorophyll biosynthetic pathways. 4 

### Protox exists in both plants and animals and the enzyme from both sources has been shown to be highly sensitive to many LDPHs. 5

4 Matringe, M., J.-M. Camadro, P. Labbe, and R. Scalla. 1989. Protoporphyrinogen oxidase as a molecular target for diphenyl ether herbicides. Biochem. J. 260 : 231-235.

5 Birchfield, N.B., and J.E. Casida. 1997. Protoporphyrinogen oxidase of mouse and maize: Target site selectivity and thiol effects on peroxidizing herbicide action. Pesticide Biochemistry and Physiology 57 , 36-43

.

### LDPH protox inhibition in plants results in a rapid accumulation of protoporphyrin IX, a phototoxic heme and chlorophyll precursor. In the presence of light, pr otoporphyrin IX is a powerful generator of singlet oxygen which in plants causes lipid membrane peroxidation leading to a rapid loss of turgidity and folia r burns. LDPH exposure in mammals has been shown to result in excretion of porphyrins in urine (porphynuria) and f eces, increased liver weight, elevated blood porphyrin levels, developm ental abnormalities, and cancer. Humans with a hereditary protox disorder (v ariegate porphyria) which results in lowered protox activity exhibit many symptoms similar to LDPH exposure in addition to photosensitivity. However, photosensitivity is not a comm only reported symptom of LDPH exposure in animals.

An LDPH-induced occurrence of phototoxicity in rats 6 

### and increased cytotoxi city to human skin cells grown in culture in the presence of light and an LDPH 7 

### have been reported but many other LDPH toxicity studies make no mention of phototoxicity in animals. The scarcity of phototoxicity data in animals could result from physiological or biochemical distinctions from plants. For instance, animals exposed to LD PHs may not normally accumulate protoporphyrin IX in their epidermis. However, phototoxicity may not be reported in many LDPH toxicity tests because of relatively low light conditions in laboratories and/or protection afforded by the

animals' fur or feathers. Animals without fur or feathers existing in sunny environments would be expected to be at highest risk for potential phototoxic effects.

The Aquatic Biology Tech Team (ABTT) recomme nds that phototoxicity studies be conducted on herbicides with this mode of action to determ ine if animals exposed to LDPHs and intense light (similar to sunlight) show increased toxicity relative to controls ex posed to LDPHs and low intensity light. The results of these studies will help to determine if animals that are exposed to sunlight in LDPH use areas are at higher ri sk than guideline toxi city studies suggest.

The ABTT is requesting that a LDPH phototoxici ty protocol be submitted for review and agreement by EFED and the registrant prior to study initiation. Protocols for standard toxicity tests have also been published. 8 

### In nature, fish and other aqua tic organisms are expected to be exposed to LDPHs through run-off and spray drift. Aquatic organisms inhabiting small, shallow water bodies, exposed to high levels of solar radiat ion would be expected to be at greatest risk for potential phototoxic effects. Therefore, the ABTT is requesting a small fish species be used in a phototoxicity assay to assess the potential of light to increase LDPH toxicity.

6 Halling, B.P., D.A. Yuhas, V.F. Fingar, and J.W. Winkleman. 1994. "Protoporphyrinogen oxidase inhibitors for tumor therapy" in Porphyric Pesticides: Chemistry, Toxicology, and Pharmaceutical Applications , (S.O. Duke and C.A. Rebeiz, Eds.) pp. 280-290, Ameri can Chemical Society Symposium Series 559, Am. Chem. Soc., Washington, D.C., 1994.

7 Birchfield, N.B. Protoporphyrinogen Oxidase as a Herbicide Target: Characterization of the
[ 3 H]Desmethylflumipropyn Binding Site . Dissertation. University of California, Berkeley. 1996.

8 American Society for Testing and Ma terials. 1994. Standard guide for conducting the frog embryo teratogenesis assay- Xenopus . E 1439-91. In Annual Book of ASTM Standards , Vol 11.5, pp. 825-835. Philadelphia,

PA.



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### The ABTT requests that the study adequately address the following issues and suggests the paper, "Photoenhanced Toxicity of a Carbamat e Insecticide to Early Life Stage Anuran Amphibians", 5 

### and other studies in the peer-reviewed sc ientific literature serve as sources of additional guidance:

Species The fathead minnow may be an appropriate test sp ecies because of existing toxicity protocols which may be adapted for this study.

Exposure duration A subchronic exposure duration would be adequate for proof of principle. A single exposure may not allow adequate time for porphyrin accu mulation, however, a life- cycle is not necessary to identify a phototoxi c effect.

Dosing A range finding study should be conducted under de fined low light conditions to identify an

LC 50 

### value and lower dose levels expected to be similar to controls. Doses used in the phototoxicity study should not be expected to result in significant mortality in low light controls.

Dissolved concentrations of the test chemical should be confirmed by an appropriate analytical

method.

Endpoints

Behavioral observations should be made in addition to measur ements of mortality, growth, weight, morphology, and appearance. Ideally, measurements of protoporphyrin and heme concentrations in the blood and protox activity in the liver of each test organisms should be

made.

Light sources Artificial light may be preferred to natural light th at will vary in different regions and seasons as

well as with weather. If artifici al light is used, the light should re semble full, natural sunlight as closely as possible, particularly around 400 nm. The most important wavelength for porphyrin induced phototoxicity in ~400 nm. No matter what the light source, the duration and intensity of UV and visible light should be reported at all wavelengths (200-800 nm). At this point EFED does not have a specific recommenda tion for an artificial light source.

Dark, light, and positive controls As this study is intended to identify potential e ffects of light on LDPH to xicity, an appropriate study protocol should include a da rk, or low light, control group. Another group not exposed to chemicals but exposed to full light should be incl uded (a full light control). In addition to the dark and light controls, a positive control group using protoporphyrin IX may be useful.

Exposure chambers and light filters Light intensity should be measured inside test ch ambers if glass or any other material is placed between the light source and the test animals. Any filters should be cured under the study light for 72-hours prior to study initiation to ensure consistent transmittance.

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### 65 of 67 ATTACHMENT.

The following list of herbicides are believed to act by inhibiting protoporphyringen oxidase in the heme and chlorophyll biosynthetic pathway.

acifluorfen

azafenidin carfentrazone-ethyl flumiclorac-pentyl

flumioxazin fluthiacet-methyl

fomesafen

lactofen oxadiargyl

oxadiazon oxyfluorfen

sulfentrazone

thidiazimin