UNITED STATES ENVIRONMENTAL 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 (EFED) has completed the preliminary problem 

formulation (attached) for the ecological risk, environmental fate, and endangered species 

assessment to be conducted as part of the Registration Review of the herbicide, flumicloracpentyl (PC Code 128724). Functioning as the first stage of the risk assessment process for 

registration review, this problem formulation provides an overview of what is currently known 

about the environmental fate and ecological effects associated with flumiclorac-pentyl and its 

degradates. It also describes the preliminary ecological risk hypothesis and analysis plan for 

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evaluating and characterizing risk to non-target species in support of the registration of 

flumiclorac-pentyl. 

Attachment: Problem Formulation for the Environmental 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 Assessments 

in Support of the Registration Review of Flumicloracpentyl

Flumiclorac-pentyl (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 Patterns 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 Properties of Flumiclorac-pentyl ....................................................... 12 

Table 5 Summary of sensitive endpoints for aquatic organisms under consideration for use in the 

risk assessment for flumiclorac-pentyl* ....................................................................................... 16 

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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 for 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 Phototoxicity Study Protocol for Light-Dependent 

Peroxidizing Herbicides................................................................................................................ 62 

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1. Purpose 

The purpose of this problem formulation is to provide 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 derivative herbicide. This document will provide a 

plan for analyzing data relevant to flumiclorac-pentyl and for conducting environmental fate, 

ecological risk, and endangered species assessments for its registered uses. Additionally, this 

problem formulation is intended to identify data gaps, uncertainties, and 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, Fungicide, and Rodenticide Act (FIFRA), all pesticides distributed 

or sold in the United States generally must be registered by the United States Environmental 

Protection Agency (U.S. EPA). To determine whether a pesticide can be registered, the U.S. 

EPA evaluates its safety to non-target species based on a wide range of environmental and health 

effects studies. In 1996, FIFRA was amended by the Food Quality Protection Act, and EPA was 

mandated to implement a new program for the periodic review of pesticides, i.e., registration 

review1. The registration review program is intended to ensure that, as the ability to assess risk 

evolves and as policies and practices change, all registered pesticides continue to meet the 

statutory standard of no unreasonable adverse effects to human health and the environment. 

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

new registration review program, the Agency periodically reevaluates pesticides to make sure 

that as change occurs, products in the marketplace can be used safely. 

As part of the implementation of the new Registration Review program pursuant to Section 3(g) 

of FIFRA, the Agency is beginning its evaluation of flumiclorac-pentyl to determine whether it 

continues to meet the FIFRA standard for registration. This problem formulation for the 

environmental fate and ecological risk assessment 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 Effects Science Chapter, Environmental Fate 

and Ecological Risk Assessment, Registration for New Use for Flumiclorac-pentyl 

• October 19, 2005 Flumiclorac-pentyl; Tolerance Reassessment 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 Dietary 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-listed 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 ester] is a N-phenylphthalimide derivative herbicide used for the 

control of broadleaf weeds. Its mode of action is through the accumulation of porphyrins in 

susceptible plants. In turn; the photosensitizing action of accumulated porphyrins may cause 

membrane lipid peroxidation which leads to irreversible 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 areas such as industrial 

sites, airports, military installations, roadsides, rights of way, and other similar areas to control a 

selected group of broadleaf weeds, specifically morning glory and velvet leaf. According to the 

Health Effects Division (HED) Label Data report (US EPA 2008), the maximum nonagricultural use rate is 0.028 lb ai/A, however, the Biological Economics Analysis Division 

(BEAD) was unable to find Screening Level Usage Analysis (SLUA) data for non-agricultural 

national use estimates. 

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Table 1 - Cropland Use Patterns for Flumiclorac-pentyl

Crop1 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 usage of flumiclorac-pentyl. According to the 

table provided by the Biological Economics Analysis Division in OPP (BEAD), the major uses 

were on corn, cotton, and soybeans. 

The uses marked with the “+” symbol 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 registered formulations include soluble concentrate, 

dust, wettable powder, granular, liquid, and pelleted or tableted (BEAD, August, 2008). 

Table 2 Screening Level Estimates of Agricultural 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 percent 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 five FIFRA Section 3 labels. All 

active products are registered by Valent USA Corp. 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 flumiclorac-pentyl were found in OPPIN and can be 

found in Table 3. 

The herbicide can be applied as a liquid, emulsifiable concentrate, and as a wettable powder. 

Flumiclorac-pentyl is applied via aircraft, groundspray, back pack sprayer, ground boom, hand 

held, and band sprayer at various application rates depending on the application method, crop, 

and applicable label. The products containing flumiclorac-pentyl have a wide assortment of 

active ingredient concentrations ranging 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 single 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 product/acre x 1gallon/128 oz conversion factor x 0.86 lbs ai/gallon = 0.054, 0.11 and 0.094 

lbs ai./Acre. 

2 Calculated from 7 or 10 fl oz product/acre x 1gallon/128 oz conversion factor x 0.7 lbs ai/gallon = 0.038 or 0.055 lbs ai./Acre. 

3 Calculated from 64 or 96 fl oz product/acre x 1gallon/128 oz conversion factor x 0.056 lbs ai/gallon = 0.028 or 0.042 lbs 

ai./Acre. Non agricultural maximum rate from BEAD. 

3.3. Environmental Fate and Transport 

Laboratory and field data suggest that parent flumiclorac-pentyl is not persistent or mobile in soil 

and aqueous environments. While aerobic aquatic 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 degrades into a number of bulky anionic 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-fluorophenoxyacetate (AFE) the final product. At pH 7, 

this moiety degrades further to 5-amino-2-chloro-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 (IMCA), and N-(5-carboxymethoxy-4-chloro-2-

fluorophenyl)-3,4,5,6-tetrahydrophthalamic acid (IMCA-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 metabolized further and become bound residues. 

In the presence of light, further breakdown and/or mineralization of flumiclorac-pentyl 

degradates occurs, although the half-life of parent flumiclorac-pentyl appears to be unaffected. 

While less than 0.5% of the applied radioactivity is released as 14CO2 from flumiclorac systems 

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

released 22.81% of the applied radioactivity as 14CO2. This effect is less striking on soil: 7.32% 

of the applied radioactivity was mineralized to 14CO2 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 (DWA) for flumicolorac-pentyl (EPA 2005), the 

assumption was that the residues of interest are parent flumiclorac-pentyl (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 available, 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-pentyl residues at the 

surface is less clear. In radiolabeled lysimeter studies, nearly 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 volatilization is based only on one 

study and it can not be determined if volatilization is occurring, and if so, what degradates or 

percent parent is contributing to this possible volatilization. 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 metabolism 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 Kentucky, 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 original molecule, and their off-site movement may 

represent a hazard to non-target organisms. However, the flumiclorac-pentyl degradates N-(4-

chloro-2-fluoro-5-pentoxycarbonylmethoxypheny1-3,4,5,6-tetrahydrophthalamic acid (031 -

HA); and pentyl 5-amino-2-chloro-4-fl uorophenoxyacetate (AFE) appear to be more susceptible 

to photolysis when they are in solution, and would be unlikely to persist for more than a few 

days in an aquatic environment. A summary 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-m3

/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 

Koc (milliliters/gram) 30 Pesticide Properties 

database 05/26/2009 

Log octanol-water partition coefficient (log Kow) 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, flumiclorac-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 short 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 data on the aquatic persistence with the degradate 

IMCA was not available, therefore, 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 any 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 (TMDL) have been developed for flumicloracpentyl, based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?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 extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration 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 quantitatively or qualitatively in pesticide risk 

assessments.

4. Receptors 

The receptor is the biological entity that is exposed to the stressor (U.S. EPA 1998). Consistent 

with the process described in the Overview Document (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 variety of species (receptors) included under these 

taxonomic groupings. 

Acute toxicity data from studies submitted by pesticide 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 data submitted by the registrant. 

Additional studies include toxicity on the technical grade active ingredient, degradates, and when 

available, formulated products (e.g., “Six-Pack” studies). The open literature studies are 

identified through EPA’s ECOTOXicology (ECOTOX) database (U.S. EPA 2009), which 

employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial 

plants, and wildlife. The evaluation of both sources of data 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 functional characteristics of the 

affected communities. Open literature data from ECOTOX on flumiclorac-pentyl was completed 

and resulted in no acceptable studies for inclusion in the risk assessment at this time. 

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A summary of the aquatic and terrestrial toxicity data used to derive 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 with flumiclorac-pentyl and a description of 

ecosystems potentially at risk are provided in Sections 4.3 and 4.4, respectively.

4.1. Effects to Aquatic Organisms 

A summary of sensitive aquatic toxicity data from 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-pentyl is 0.189 mg/L (MRID 42187405). In discussions 

with Ecological Effects Branch (EEB) staff on January 18, 1989 and on February 27, 1992, the 

registrant indicated that preliminary aquatic animal testing with flumiclorac-pentyl indicated they 

had problems achieving solubility within the parameters outlined in guideline testing. They were 

unable to achieve solubility greater 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 flumiclorac-pentyl. Therefore, 

alternative co-solvents and solvent concentrations for use in aquatic animal testing were 

requested by the registrant. EEB staff indicated that the registrant should provide justification 

for these extra measures and would view favorably a well designed study which resulted in a 

dose response. The registrant provided information for the use of dimethyl formamide: 

polyoxyethylene hydrogenated castor oil (1:1, DMF:HCO-40), and toxicity data for bluegill 

sunfish and rainbow trout from this solvent mixture (MRID 42169808). Based on this 

information, the aquatic studies were conducted 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 toxicity 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-solvent 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 delivery system. No precipitate was reported in the 96-hour acute 

mysid toxicity study. Test solution appearance was not reported for either the acute rainbow 

trout or bluegill toxicity study. So while a presence 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 other toxicity studies. For all studies in which 

precipitate was observed, an attempt to remove the precipitate from the analytical samples prior 

to analysis (ex. centrifugation, filtering) was not reported. Therefore, it is not known what the 

actual dissolved flumiclorac-pentyl concentration in the test systems were, as the presence of 

precipitate during analysis could overestimate the actual exposure concentration. All of these 

studies were conducted above the reported solubility of 0.189 mg/L for flumiclorac-pentyl, and 

therefore, the NOAEC level for all aquatic studies are above this reported water solubility. LC50

values were obtained for the bluegill sunfish, rainbow trout and mysid invertebrate, but with the 

exception of the mysid toxicity data, actual aquatic exposure concentrations are uncertain. A 

LC, EC50 concentration could not be determined for the sheepshead minnow or Daphnia magna 

toxicity study, respectively, due to a lack of dose response. Since this uncertainty exists for these 

aquatic studies in which precipitate was observed these studies are classified as supplemental. 

Also, the 96-hour oyster shell growth deposition study was classified 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 measured), 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 there 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-pentyl 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 structure to parent flumiclorac-pentyl indicates it 

may be phytotoxic. The concentration of IMCA tested was based on the maximum application 

of flumiclorac-pentyl and the degradate IMCA comprising 53% of the parent flumiclorac-pentyl 

(up to 1 day post-treatment), therefore, the maximum application rate 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 concentration. The aquatic vascular plant, Lemna gibba,

toxicity study using IMCA at one concentration showed a 3.3 and 12% increase in frond number 

and dry weight when compared to the negative control. The nonvascular, green algae toxicity 

study at the IMCA limit concentration showed a 4.1% decrease in cell density compared to the 

negative control. 

There is no chronic toxicity data for freshwater fish or invertebrates, or estuarine-marine fish or 

invertebrates. 

In addition, flumiclorac-pentyl is a light-dependent peroxidizing herbicide (LDPH), and may be 

very toxic to living organisms. Therefore, The Aquatic Biology Tech Team (ABTT) 

recommends that phototoxicity studies be conducted on herbicides with this mode of action to 

determine if animals exposed to LDPHs and intense 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 Peroxidizing Herbicides, Dated March 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 flumiclorac-pentyl’s mode of action, adverse effects to 

aquatic organisms under natural sunlight are expected. Effects to estuarine-marine fish and 

aquatic-phase amphibians is also expected based 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 LC50 

> 0.189 1

1.12

(mortality) 

42169806 

Supplemental Moderately Toxic3

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 LC50

> 0.189 1

> 24 2

(mortality) 

42825809 

Supplemental NA4 

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 NA4 

Waterflea 

 (Daphnia magna) 

TGAI 

Full 

Lifecycle NOAEC No Data No Data No Data 

Estuarine Marine Invertebrates 

Mysid Shrimp 

(Americamysis bahia) 

TGAI

96 hours LC50

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 NA4 

Green Algae 

Selenastrum capricornutum 96 hours NOAEC 0.035 (IMCA) 43240800 

Acceptable NA4

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

Acceptable NA4

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

Acceptable NA4

TGAI=technical grade active ingredient; LC50 = median lethal concentration; NOAEL=no observable 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 ai/L). Actual test concentration not known due to the presence of 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 measured 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 (aquatic nonvascular and 

vascular plants with IMCA) toxicity classification could not be determined. 

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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 practically nontoxic to birds, mammals, and terrestrial 

invertebrates. 

Acute, subchronic, and chronic toxicity 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 exposure. 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 high dose levels. Effects included 

urinary incontinence, increased water consumption, increased urine volume, increased kidney 

weights in the females, and increased squamous epithelial 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. Flumiclorac-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 avian studies. Reduced egg 

laying an regressed ovaries and small testes were observed in the chronic study with the mallard 

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

Based on the degradation of parent flumiclorac-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 maximum application rate of flumiclorac-pentyl 

and the expected maximum concentration of the degradate IMCA (53% of the flumicloracpentyl) to be present. The study was conducted 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 comparison using pooled controls. Based on a 

reduction in shoot lengths, the onion and oat were statistically significant compared to the 

negative control and the shoot height reductions ranged from -9.8 to 15% compared to the 

negative control. Decreases in seedling emergence 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 emergence study which is a sensitive 

endpoint for evaluating toxicity. The vegetative vigor study was conducted using parent 

flumiclorac-pentyl. The most sensitive species based on phytotoxicity was the tomato. 

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Table 6 Summary of sensitive toxicity endpoints for terrestrial 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 

LD50

> 5,000 mg/kg (mortality) 42169812/ 

Acceptable 

Practically 

Nontoxic 

Rat 

(Rattus 

norvegicus) 

V-23031 0.83 EC 

LD50

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 NA1 

Birds

Bobwhite Quail

(Colinus 

virginianus) 

TGAI 

LD50 > 2131 mg ai/kg-bw (no mortality) 42169802/ 

Acceptable 

Practically 

Nontoxic 

Bobwhite Quail

(Colinus 

virginianus)/ 

Mallard Duck 

(Anas 

platyrhynchos) 

TGAI 

8-day 

LC50

>5322 mg ai/kg-diet (no mortality) 

42169803, 

42169804/ 

Acceptable 

NA1 

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 NA1 

Terrestrial Invertebrates 

Honey Bee 

(Apis mellifera)

TGAI 

LD50

> 106 μg/bee 

(no mortality) 

42169841/ 

Acceptable 

Practically 

Nontoxic 

Terrestrial Plants 

EC25 > 0.046 lb IMCA/Acre Seedling 

Emergence 

Seedling 

Emergence NOAEC < 0.046 lb IMCA/Acre2

43258001/ 

Acceptable NA1 

EC25

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 NA1 

* Data in this table may be used in the risk assessment, but it will not necessarily be used to calculate risk quotients. 1

 Toxicity Classification not applicable for study. 2

 Due to study conducted as limit test, and differences greater than 5% compared to control for both emergence and shoot 

height, a definitive NOAEC could not be determined. 

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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 that incident, there was damage to a soybean crop after application 

of a product containing flumiclorac-pentyl. However the report notes that the damage was 

believed to have been caused by residual contamination from a prior use of the tank involving 

2,4-D, and therefore was not due to flumiclorac-pentyl. Thus, the incident data give no evidence 

of this active ingredient causing any problems to non-target species. 

4.4. Ecosystems Potentially at Risk 

The ecosystems at risk are often extensive in scope; therefore, it may not be possible to identify 

specific ecosystems during the development of a nation-wide ecological risk assessment. 

However, in general terms, terrestrial ecosystems potentially at risk could include the areas that 

are immediately adjacent to treated water that may receive drift or runoff during flooding. Areas 

adjacent to the treated water could include cultivated fields, fencerows and hedgerows, 

meadows, fallow fields or grasslands, woodlands, riparian habitats and other uncultivated areas. 

Aquatic ecosystems potentially at risk include treated water bodies and water bodies adjacent to 

or down stream from, the treated water and could include impounded bodies such as ponds, lakes 

and reservoirs, or flowing waterways such as streams or rivers. For uses in coastal areas, aquatic 

habitat also includes marine ecosystems, including estuaries. 

5. Assessment Endpoints 

Assessment endpoints represent the actual 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 ecological entities may include the following: birds, 

mammals, terrestrial-phase amphibians, reptiles, freshwater fish and invertebrates, aquatic-phase 

amphibians, estuarine/marine fish and invertebrates, terrestrial plants, insects, 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 must reach ecological receptors in biologically 

significant concentrations. An exposure pathway is the means by which a pesticide moves in the 

environment from a source to an ecological receptor. For an ecological pathway to be complete, 

it must have a source, a release mechanism, an environmental transport medium, a point of 

exposure for ecological receptors, and a feasible route of exposure. 

The conceptual model for flumiclorac-pentyl provides a written description and visual 

representation of the predicted relationships between flumiclorac-pentyl, potential 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-tetrahydrophthalimido) phenoxyacetic acid (IMCA) and 

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 20 of 67

this degradate is mobile and expected to be in the environment, both flumiclorac-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 relationship among the stressor, exposure, and 

assessment endpoint response along with the rationale for their selection. For flumicloracpentyl, the following overall ecological risk hypothesis is being employed for this ecological risk 

assessment: 

Based on the application methods, mode of action, fate and transport, and the sensitivity 

of non-target aquatic and terrestrial species, flumiclorac-pentyl and its degradate IMCA 

has the potential to reduce survival and growth in non-target terrestrial plants when used 

in accordance with the current label. These 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 peroxidizing herbicide), and known 

sensitivity of non-target aquatic and terrestrial species to this class of chemicals 

(Appendix C), flumiclorac-pentyl and its degradate IMCA has the potential to reduce 

survival, growth and reproduction of non-target aquatic and terrestrial animals. 

The specific exposure routes quantitatively evaluated include, water concentrations and runoff 

and spray drift. The following hypotheses reflect these exposure pathways. 

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

invertebrates, and plants. 

• Flumiclorac-pentyl residues on plants and other dietary surfaces deposited with spray 

drift may affect terrestrial organisms, and 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 transport mechanisms of flumiclorac-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 Conceptual Model for Flumiclorac-pentyl 

Flumichlorac-pentyl applied as a ground/aerial spray to an agricultural field, and its degradate IMCA 

Source/ Transport Pathways 

Direct Deposition 

Spray Drift 

Runoff Erosion 

Source/ Exposure Media Exposure Route Receptors Attribute Changes 

Terrestrial Food Residues (foliage, fruit, insects) 

Upland Foliage/Soil 

Riparian/ Wetland Foliage/Soil 

Receiving Water Body Sediment 

Ingestion Direct contact/ 

Root Uptake 

Direct contact/ Root Uptake 

Uptake/ Adsorption 

Gil/ Integument Uptake 

Terrestrial Vertebrates 

Terrestrial Upland Plants 

Wetland/ Riparian Plants 

Aquatic Plants 

Aquatic Verts/Inverts 

Individual Animals Reduced survival Reduced growth Reduced Reproduction. 

Individual Plants Seedling emergence Vegetative vigor 

Plant Population Reduced PopulationGrowth

Individual Verts/Inverts Reduced survival Reduced growth Reduced Reprod.

Stressor 

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7. Analysis Plan 

In order to address the risk hypothesis, the potential for adverse effects on the environment is 

estimated. The use, environmental fate, and ecological effects of flumiclorac-pentyl and IMCA 

are characterized and integrated to assess the risks. This is accomplished using a risk quotient 

(ratio of exposure concentration to effects concentration) approach. Although risk is often 

defined as the likelihood and magnitude of adverse ecological effects, the risk quotient-based 

approach does not provide a quantitative estimate of likelihood and/or magnitude of an adverse 

effect. However, as outlined in the Overview Document (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 revisited and may be revised depending 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 degradate 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 mixtures of multiple active 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 containing more than one active ingredient), each active 

ingredient is subject to an individual risk assessment for regulatory decision regarding the active 

ingredient on a particular use site. If effects data are available for a formulated product 

containing more than one active ingredient, the data may be used qualitatively or quantitatively 

in accordance with the Agency’s Overview Document and the Services’ Evaluation 

Memorandum (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 assessment. It is expected that the toxic effect of 

flumiclorac-pentyl, in combination with other pesticides used in the environment, is likely to be a 

function of many factors including but not necessarily limited to: (1) the exposed species, (2) the 

co-contaminants in the mixture, (3) the ratio of flumiclorac-pentyl and co-contaminant 

concentrations, (4) differences in the pattern and duration of exposure among contaminants, and 

(5) the differential effects of other physical/chemical characteristics of the receiving waters (e.g.

organic matter present in sediment and suspended water). Quantitatively predicting the 

combined effects of all these variables on mixture toxicity to any given taxa with confidence is 

beyond the capabilities of the available data and methodologies. However, a qualitative 

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discussion of implications of the available pesticide mixture effects data on the confidence of 

risk assessment conclusions will be addressed 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 conclusions will be made based on maximum 

application rates for flumiclorac-pentyl. Measures of exposure are based on aquatic and 

terrestrial models that predict estimated environmental 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 input 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 flumiclorac-pentyl through runoff 

and spray drift. PRZM simulates pesticide application, movement and transformation on an 

agricultural field and the resultant 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 agricultural field that drains into an adjacent 1-hectare water body 

that is 2 meters deep (20,000 m3

 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 of direct 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 applications, the T-REX model (Terrestrial Residue EXposure 

model) is used to predict dietary exposure to flumiclorac-pentyl residues on foliar surfaces and 

insects using the Kenaga nomogram as modified by Fletcher (Hoerger and Kenaga 1972; 

Fletcher et al. 1994). Exposure estimates for terrestrial animals 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 based on a large set of 

actual field residue data. The upper limit values from the nomograph represent the 95th percentile 

of residue values from actual field measurements (Hoerger and Kenega 1972). The Fletcher et 

al. (1994) modifications to the Kenega nomograph are based on measured field residues from 

249 published research papers, including information 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 

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the appropriate PRZM/EXAMS parameter values for modeling the percent drift corresponding to 

the buffers indicated on the label. 

7.3. Measures of Effect 

Ecological effects data are used as measures of direct 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) provides more ecological effects data in an 

attempt to bridge existing data gaps. ECOTOX is a source for locating single chemical toxicity 

data and potential chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. 

ECOTOX was created and is maintained by the U.S. EPA, Office of Research and Development, 

and the National Health and Environmental Effects 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 mortality) 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 coloration). Quantitative assessments of risks, though, are limited to 

those endpoints that can be directly linked to the Agency’s assessment endpoints of impaired 

survival, growth and reproduction. 

The assessment of risk for direct effects to non-target organisms makes the assumption that 

toxicity of flumiclorac-pentyl to birds is similar to terrestrial-phase amphibians and reptiles. The 

same assumption is made for fish and aquatic-phase amphibians. 

The acute measures of effect used for animals in this assessment are the LD50, LC50 and EC50. 

LD stands for "Lethal Dose", and LD50 is the amount of a material, given all at once, that is 

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

and LC50 is the concentration of a chemical that is estimated to kill 50% of the test organisms. 

EC stands for “Effective Concentration” and the EC50 is the concentration of a chemical that is 

estimated to produce a specific effect in 50% of the test organisms. Endpoints for chronic 

measures of exposure for listed and non-listed animals are the NOAEL/NOAEC and NOEC. 

NOAEL stands for “No Observed-Adverse-Effect-Level” and refers to the highest tested dose of 

a substance that has been reported to have no harmful (adverse) effects on test organisms. The 

NOAEC (i.e., “No-Observed-Adverse-Effect-Concentration”) is the highest test concentration at 

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

the No-Observed-Effects-Concentration. For non-listed plants, only acute exposures are 

assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic plants); for listed plants either the 

NOAEC or EC05 is used. 

 

2

 http://www.epa.gov/oppefed1/general/databasesdescription.htm#eiis 

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7.4. Integration of Exposure and Effects 

Risk characterization is the integration of exposure and ecological effects characterization to 

determine the potential ecological risk from the use of flumiclorac-pentyl as a herbicide and the 

likelihood of direct and indirect effects to non-target organisms in aquatic and terrestrial habitats. 

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

ecological effects on non-target species. For the assessment of flumiclorac-pentyl risks, the risk 

quotient (RQ) method is used to compare exposure and measured toxicity values. EECs are 

divided by acute and chronic toxicity values. The resulting RQs are then compared to the 

Agency’s Levels of Concern (LOCs) (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 the 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 Panels3 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 threatened and/or endangered (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 associated with the registration 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 indirect effects. The Agency’s approach 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 exposure 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 sublethal effects available in the 

effects literature. Therefore, the action area extends to a point where environmental exposures 

are below any measured lethal or sublethal effect threshold for any biological entity at the whole 

 

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

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organism, organ, tissue, and cellular level of organization. In situations where it is not possible 

to determine the threshold for an observed effect, the action area 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 835.4300). This study is needed to assess the 

degradation of flumiclorac-pentyl and the formation and degradation of the IMCA in the 

aquatic environment. 

• According to EFED’s BEAD Laboratory contact 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 method being submitted by the registrant for 

detecting the parent and IMCA in water (Guideline Number: 835.6100). 

No measured organic carbon partitioning 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 provide 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, submitted and required to assess 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 fish toxicity study (Guideline 850.1400) under UV enhanced light 

with the fathead minnow (Study previously required under GDCI-128724-26284, but not yet 

submitted) 

• Tier II acute non-vascular aquatic plant growth (Guideline 850.5400) with the degradate 2-

chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido) phenoxyacetic acid (IMCA) for three 

species of non-vascular aquatic plants 

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

with Daphnia magna 

• aquatic invertebrate life-cycle 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 freshwater invertebrate study would be required based on a half-life in 

sediment less than 10 days in the aerobic soil 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) (Pesticide Fact Sheet: Flumiclorac-pentyl, 

11/18/1994). 

Table 7 Available Ecological Effects Data for 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 

850.2200 TGAI 42169803 Acceptable 

Avian dietary 

toxicity Mallard Duck TGAI 42169804 Acceptable 

No 

Bobwhite 

Quail 

850.2300 TGAI 42825805 Acceptable 

Avian reproduction 

Mallard Duck TGAI 42825806 Acceptable 

No 

850.3020 

Honeybee acute 

contact toxicity 

Honeybee TGAI 42169841 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 Acceptable 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 

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Table 8 Available Ecological Effects Data for Aquatic Animals Exposed to Flumicloracpentyl and Remaining Data Gaps 

Guideline Number 

Description 

Species TGAI/ 

TEP 

MRID/ 

Accession 

Classification Data 

Gap? 

Comments 

Bluegill 

Sunfish 

850.1075 TGAI 42169806 Supplemental 

Freshwater fish – 

Acute toxicity 

Data needed for 1 

coldwaterspecies and 1 

warmwater species. Data 

needed for TEP needed if 

applied directly to water, 

maximum EEC≥0.5 LC50, 

or end product enhances 

toxicity 

Rainbow 

Trout 

TGAI 42169807 Supplemental 

Yes1 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 LC50, or end 

product enhances 

toxicity.

Sheepshead 

Minnow 

TGAI 42825809 Supplemental Yes1 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 toxicity2

Waterflea TGAI 42169808 Supplemental Yes1 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 Yes4 850.1025, 850.1035, 

850.1045, 850.1055 

Estuarine/Marine 

invertebrates – 

Acute toxicity3

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. 

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Guideline 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 Cycle5

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 LC50

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 flumicloracpentyl, therefore toxicity could be 

due to the degradate IMCA. 

850.1400 

Freshwater fish – 

early life stage test6

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 test7

No data submitted Pending Not anticipated at this time due to 

LC50 being greater than reported 

water solubility and the predicted 

EEC is < 0.01 of acute LC50. 

850.1500 

Freshwater Fish – 

life cycle test8

No data submitted Pending Not anticipated at this time due to 

LC50 being greater than reported 

water solubility, flumiclorac-pentyl 

is not applied to water, and the fate 

of flumiclorac-pentyl 

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Guideline Number 

Description 

Species TGAI/ 

TEP 

MRID/ 

Accession 

Classification Data 

Gap? 

Comments 

850.1500 

E/M Fish – 

life cycle test9

No data submitted Pending Not anticipated at this time due to 

LC50 being greater than reported 

water solubility and the predicted 

EEC is < 0.01 of acute LC50. 

850.1735 

Whole sediment 

acute freshwater 

invertebrate10

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 

invertebrates11

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 

marine12

No data submitted Yes The environmental degradation 

half-lives are less than 10 days. 

No data are needed.

850.5400 

Algal toxicity13

Green Algae IMCA 43240800 Acceptable Yes* Only one species was tested (green 

algae), and testing is required for 

blue-green algae, 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 43251201 Acceptable No 

* Data Call-In for study requested 

Abbreviations: E/M = estuarine/marine; TEP=typical end 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 acceptable test solution appearance (freshwater fish) and 

analytical methods (all studies). 

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

LC50, or end product enhances toxicity 

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

EEC≥0.5 LC50, 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 

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analytical 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 LC50 < 

1 mg/L, or the EEC is ≥0.01 of acute LC50. 

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 LC50 < 

1 mg/L, or the EEC is ≥0.01 of acute LC50. 

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 LC50 and the half-life > 10days and if any of the following exist: the 

low Kow ≥3 or the KOC≥1000. Data required for E/M when applied directly to E/M environment. 

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

Due to the uncertainties in the actual water concentrations of the aquatic toxicity studies, with the 

exception of the acute mysid shrimp toxicity study, these studies are 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 (filtering 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 (Guideline 850.2100): Passerine Species 

Acceptable acute avian oral toxicity data were submitted for exposures of bobwhite quail to 

flumiclorac-pentyl; however, data are not available for passerines, which are required under the 

new 40 CFR Part 158 data requirements for conventional pesticides (72 FR 60934; USEPA 

2007b). The new Part 158 data requirements specify 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 study 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. Therefore an early life-cycle study with flumiclorac-pentyl is requested. 

Due to structurally similarities to parent flumiclorac-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 terrestrial birds and mammals. This study was already required in 

GDCI-128724-26284. The registrant Valent USA Corporation has joined the registrant light 

dependent peroxidizing herbicide workgroup (LDPH WG). This LDPH WG is currently 

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working with EFED in implementing toxicity testing to evaluate chronic fish toxicity from light 

dependent peroxidizing herbicides 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-cycle toxicity data are required under 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 occur. 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 invertebrate 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 predicted EEC concentration in water and the 

Ecological Effects Branch (now EFED) recommended this request be granted, this study is now 

being requested. In addition to the fate of flumiclorac-pentyl and IMCA described above, the 

LC50 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 nominal. 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 estuarine-marine species if the acute LC50 is less than 1 mg/L, and 

the pesticide half-life in water is greater than four days. Therefore, an aquatic estuarine-marine 

invertebrate life cycle study with the mysid shrimp (Americamysis bahia) using the degradate 

IMCA is requested. 

Aquatic Plant Studies (850.5400)

Toxicity data for some non-vascular aquatic plants are not available, as only a study with the 

green algae was submitted. Based on the 40 CFR Part 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 flumiclorac-pentyl. This data gap must be filled, and 

non-target aquatic plant data for algae plants (OPPTS Guideline 850.5400) are required for the 

degradate IMCA at the Tier II level at this time. In the absence of Tier II data, EFED will 

assume risk to non-vascular aquatic plants. 

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Terrestrial Plant Toxicity, Tier II Seedling Emergence (850.4225) 

A Tier I seedling emergence limit test was conducted 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 were statistically significant compared to the 

negative control and the shoot height reductions ranged from -9.8 to 15% compared to the 

negative control. Decreases in seedling emergence 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 emergence study which is a sensitive 

endpoint for evaluating toxicity. Based on the 40 CFR Part 158 data requirements, Tier II nontarget terrestrial plant data are required for known phytotoxins (herbicides). This data gap must 

be filled, and non-target terrestrial plant data (OPPTS Guideline 850.4225) are required for the 

degradate IMCA at the Tier II level at this time. A Tier II study will allow for the determination 

of a no observed adverse effect concentration (NOAEC) or EC05 toxicity value. A NOAEC or 

EC05 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, therefore 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 method for detecting and measuring the quantity of each 

active ingredient in their products. Validation data for both accuracy and precision should be submitted 

for all methods. Analytical methods for the active ingredient may be validated by EPA laboratories at the 

time the product chemistry data are reviewed. 

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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. Although 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 needed to accurately assess risks to these 

species. Specifically, data are required on one passerine species in addition 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 future 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, either 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 flumiclorac-pentyl and to identify whether current labeling 

is appropriate and whether further mitigation is necessary. 

 

How could the data impact the Agency’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 these 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 data will limit the flexibility the Agency and registrants 

have in complying with the Endangered Species Act and 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. 

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For 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 required 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 better refine the risks to these organisms, including the 

likelihood of potential risks to endangered species, either 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 further mitigation is necessary. 

 

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

If the data indicate that IMCA poses a significant chronic risk to aquatic invertebrates, 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 indirectly 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 restrictions, and the use of IMCA may need to be restricted 

in areas where endangered species occur unless these data are provided. 

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For IMCA Degredate 

Guideline Number: 850.1350

Study Title: Aquatic Invertebrate 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 LC50 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 LC50 is less than 1 mg/L, and the pesticide half-life in water is greater 

than four days. Therefore, an aquatic estuarine-marine invertebrate life 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 better refine the risks to these organisms, including the 

likelihood of potential risks to endangered species, either 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 further mitigation is necessary. 

 

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

If the data indicate that IMCA poses a significant chronic risk to aquatic invertebrates, 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 indirectly 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 restrictions, and the use of IMCA may need to be restricted 

in areas where endangered species occur unless these data are provided. 

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For 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 species 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 phytotoxic. 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 chemicals 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 EC05 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 further mitigation is necessary. 

 

How could the data impact the Agency’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. Therefore, 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 plant species, the Agency may explore additional decision 

options to minimize the risks to these species. The lack of these data will limit the flexibility the Agency 

and registrants have in complying with the Endangered Species Act and could result in use restrictions for 

flumiclorac-pentyl which may otherwise be avoided, or which are unnecessarily severe. 

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For IMCA Degradate 

Guideline Number: 850.4225 

Study Title: Tier II Terrestrial Plant 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 known 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 performed 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 flumiclorac-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 understanding 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 microorganisms 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 quantitative 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 flumiclorac-pentyl in these environments 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 ecological 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. 

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Guideline Number: 835.6100 

Data requirement: Environmental Chemistry Analytical Methods -- soil 

Guideline Number: 835.6200 

Data requirement: Environmental Chemistry 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 used 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 agencies to detect and monitor residues that are or are suspected to be in 

environmental compartments due to outdoor uses and accidental releases. Therefore, 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 quantitation reported in registrant-prepared validations. 

Use of flumicloric-pentyl may contaminate surface water due to runoff and drift of residues. This is 

especially true for poorly draining soils and soils with 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 flumicloric-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 for water. In addition, 

independent validations of the soils methods was not submitted. Therefore, independent validations of 

analytical methods for flumicloric-pentyl residues in soil 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 environmental 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 ensure the safety of those in proximity to releases of flumicloric-pentyl 

residues in the environment. 

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9. References 

9.1. Open Literature 

CFR 40. 2007. Code of Federal Regulations 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 instrument for estimating pesticide residues on 

plants. Environ. Tox. Chem. 13:1383-1391. 

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

Data as a Basis for Estimation of their Magnitude in the Environment. In F. Coulston and 

F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and 

Technology, Georg Thieme Publ., Stuttgart, West Germany, pp. 9-28. 

USEPA. 1993. Wildlife Exposure Factors Handbook. EPA/600/R-13/187a, Office of Research 

and Development, Washington, D.C. 

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

199998. Office of Pesticide Programs. Washington, D.C. 

U.S. EPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office 

of Research and Development, Washington, D.C. EPA/630/R-95/002F. April 1998. 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759 

U.S. EPA. 2002. Guidance for Selecting Input Parameters in Modeling the 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 Agency, 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, Registration 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 Reassessment Decision for Low Risk Pesticide; 

Notice of Availability. EPA-HQ-OPP-2005-0229-0001. October 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 Pesticide 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 Pesticide Programs. Washington, D.C. 

U.S. EPA 2005e. Flumiclorac-pentyl Chronic 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-pentyl Residue Chem for the TRED. EPA-HQ-OPP-2005-0229-

0005. September 15, 2005. Office of Pesticide Programs. Washington, D.C. 

U.S. EPA 2005g. Flumiclorac-pentyl TRED Product Chem Considerations. EPA-HQ-OPP2005-0229-0006. September 15, 2005. Office of Pesticide 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 Pesticide Programs. Washington, D.C. 

U.S. EPA 2005i. Flumiclorac-pentyl EFED Addendum No. 1 to MRID#42169844. EPA-HQOPP-2005-0229-0008. September 15, 2005. Environmental 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. Environmental 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. Pesticides; 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 Analysis Division. Office of 

Pesticide Programs. Washington, DC. 

U.S. EPA 2009. ECOTOXicology Database. Office of Research 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 National Marine Fisheries Service (NMFS). 1998. 

Endangered Species Consultation Handbook: Procedures for Conducting Consultation 

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

March 1998. 

 41 of 67
U.S. FWS/NMFS. Letter providing an evaluation by the U.S. Fish and Wildlife Service and 

National Marine Fisheries Service of an approach to assessing 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 Number: 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) Characterization of (carbon 14) Residues in Bluegill Sunfish Treated 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) Characterization of (carbon 14) Residues in Bluegill Sunfish Treated 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 (PH-(carbon 14))-S-23031 on Soil: Lab Project Number: 3313-

91-0139-EF-001. Unpublished study prepared by Ricerca, Inc. 132 p. 

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MRID: 42825827 

Korsch, B.; Shah, J. (1992) A Photolysis 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 Metabolism 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 Desorption 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 Unaged Soil Column Leaching Study with ?PH-?carbon 14||-V-23031: Lab Project Number: 

89-0383. Unpublished study prepared by Ricerca, Inc. 169 p. 

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MRID: 42169848 

Korsch, B. (1991) An Unaged Soil Column Leaching Study with ?THP-?carbon 14||-V-23031: 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-(carbon 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-23031: 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-(carbon 14))-V-23031: Revised 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-23031: 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 under 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 67
MRID: 43275101 

Nambu, K.; Radcliffe, M.; Rose, A. et al. (1994) Response 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 Flumiclorac 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) Characterization of (carbon 14) Residues in Bluegill Sunfish Treated 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) Characterization of (carbon 14) Residues in Bluegill Sunfish Treated 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 

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------------------------------------------------------------------------------------- 

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 Dietary 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.; Hoxter, 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 Acute 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 Toxicity 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 Toxicity 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 Toxicity 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. 

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Guideline: 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: 42825810 

Bettencourt, 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 (Crassostrea 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 67
MRID: 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 Toxicity 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) Primary Eye Irritation Study with Resource 80 WP in Rabbits: Lab Project 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 the 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 Irritation 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 Repeated 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 67
MRID: 45553504 

Bonnette, K. (2001) A Dermal Sensitization Study in Guinea 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 Analyses: 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 67
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. 

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 Female 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 Article Entitled "A Micro- dissection Method 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: 42169835 

Nemec, 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 67
Guideline: 83-5 Dietary: Combined Chronic Toxicity/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: Revised: 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 Germination/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 (Selenastrum capricornutum): 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 Data 

Table D1. Summary of Submitted Aquatic Toxicity Data for Flumiclorac-pentyl. Reported Solubility of flumiclorac-pentyl is 0.189 mg/L 

Study 

Type 

Test Species 

(Genus 

Species)/ Flowthrough/ 

Static 

% a.i. 

Toxicity Endpoint 

(Measured/ 

Nominal) 

Effect 

MRID (Year) 

Classification 

or Source 

Com

Freshwater Vertebrates

Acute 

850.1075 

72-3 

Bluegill Sunfish 

(Lepomis 

macrochirus)/ 

Flow-Through 

TGAI 

94.7 

96-hr LC50= 17.4 mg/L 

(measured)1 (16.5 mg ai/L) 

 LOAEC = 13 mg/L 

NOAEC = 7.8 mg/L 

96-hr LC50 > 0.189 mg/L2

Mortality 42169807 

(1989) 

Supplemental 

DER 4/29/92 

 Test solution appearan

on water solubility an

may have been pr

centrifuged or filt

concentrations. DMF:

present at maximum co

True exposure con

determined. Sublethal 

respiration, loss of equ

sublethal effects were 

below. Measured conc

78% of nominal and 

mg/L. N

54 of 67
Study 

Type 

Test Species 

(Genus 

Species)/ Flowthrough/ 

Static 

% a.i. 

Toxicity Endpoint 

(Measured/ 

Nominal) 

Effect 

MRID (Year) 

Classification 

or Source 

Com

Acute 

850.1075 

72-3 

Rainbow Trout 

(Salmo gairneri)/ 

Flow-Through 

TGAI 

94.7 

96-hr LC50= 1.1 mg/L 

(measured)1 (1.0 mg ai/L) 

 LOAEC = 0.87 mg/L 

NOAEC = 0.51 mg/L 

96-hr LC50 > 0.189 mg/L2

Mortality 42169806 

(1989) 

Supplemental 

DER 4/29/92 

Test solution appearan

on water solubility an

may have been pr

centrifuged or filt

concentrations. DMF:

present at maximum c

True exposure con

determined. Sublethal 

in surface water, on-b

equilibrium and letha

were observed at 

concentrations ranged 

and mortality occurre

No r

Estuarine/Marine Vertebrates 

Acute 

850.1075 

72-3 

Sheepshead 

Minnow 

(Cyprinodon 

variegatus)/ 

Flow-Through 

TGAI 

94.6 

96-hr LC50 > 24 mg ai/L 

(measured)1

 LOAEC > 24 mg ai/L 

NOAEC = 24 mg ai/L 

96-hr LC50 > 0.189 mg/L2

Mortality 42825809 

(1992) 

Supplemental 

DER 2/10/94 

Precipitate was obser

Water was not centr

measuring concentrat

solvent was present at m

4mL DMF:HCO-

concentrations can

sublethal effects were 

group. One mortality 

and highest treatmen

concentration probab

concentration. Measur

95% of nomin

55 of 67
Study 

Type 

Test Species 

(Genus 

Species)/ Flowthrough/ 

Static 

% a.i. 

Toxicity Endpoint 

(Measured/ 

Nominal) 

Effect 

MRID (Year) 

Classification 

or Source 

Com

Freshwater Invertebrates

Acute 

850.1010 

72-3 

Waterflea 

(Daphnia 

magna)/ 

Flow-Through 

TGAI 

94.6 

48-hr EC50 > 38.0 mg/L 

(measured)1 (35.9 mg ai/L) 

LOAEC = 3.98 mg/L 

NOAEC = 1.88 mg/L 

48-hr EC50 > 0.189 mg/L2

Mortality 42169808 

(1991) 

Supplemental 

DER 5/26/92 

Precipitate was obser

Water was not centr

measuring concentrat

solvent was present at m

4mL DMF:HCO-

concentrations cannot 

effects included letha

clinging to daphnids 

Measured concentrati

nominal. T

Estuarine/Marine Invertebrates

Acute 

850.1025 

72-3 

Eastern Oyster 

(Crassostrea 

virginica)/ 

Flow Through 

TGAI 

94.6 

96-hr EC50 > 1.8 mg ai/L 

(measured)1

96-hr EC50 > 0.189 mg/L2

Shell 

Growth 

42825811 

(1992) 

Invalid 

DER 2/10/94 

The test solution 

concentrations was clo

(DMF) was 0.5 mL DM

decreased substantially 

31% of nominal. DO 

study and was 28 to 1

deposition in controls 

56 of 67
Study 

Type 

Test Species 

(Genus 

Species)/ Flowthrough/ 

Static 

% a.i. 

Toxicity Endpoint 

(Measured/ 

Nominal) 

Effect 

MRID (Year) 

Classification 

or Source 

Com

Acute 

850.1035 

72-3 

Mysid Shrimp 

(Mysidopsis 

bahia)/ 

Flow Through 

<24-hr old 

TGAI 

94.6 

96-hr LC50 = 0.56 mg ai/L 

(measured) 

NOAEC = 0.11 mg ai/L 

Mortality 42825810 

(1993) 

Acceptable 

DER 1/28/94 

No undissolved test m

diluter system or any 

Concentration was 0

effects were loss of equ

and darkened pigm

concentrations ranged 

Low measured test con

due to degradation of 

rep

Aquatic Vascular and Nonvascular Plants 

Acute 

850.4400 

122-2 

Duckweed 

(Lemna gibba)/ 

Static-renewal 

IMCA3

98.0 

EC50 > 0.035 mg IMCA/L 

(measured) 

Increase of 3.3% and 12.8% 

for frond number and dry 

weight, respectively, for 

treatment compared to 

negative control 

Growth 43251201 

(1994) 

Acceptable 

DER 

10/24/94 

Study conducted fo

renewed on days 3, 

conducted at nominal c

Acute 

850.5400 

122-2 

Green Algae 

(Selenastrum 

capricornutum) 

IMCA3

98.0 

EC50 > 0.035 mg IMCA/L 

(measured) 

Decrease of 4.1% in cell 

density compared to negative 

control 

Growth 43240800 

(1994) 

Acceptable 

DER 

10/24/94 

Study conducted fo

conducted at nominal c

Abbreviations: TGAI = technical grade active ingredient; conc.=concentration 1 Based on mean measured test concentrations, but due to presence of precipitate or lack of reported test solution, true test concentration 2 LC or EC50 greater than reported water solubility of 0.189 mg/L flumiclorac-pentyl. 3 Due to rapid degradation of flumiclorac-pentyl and major degradate IMCA being mobile in soils and possibly bioactive, study conduc

herbicide Resource is applied at 0.0806 lb ai/A and degradate IMCA is 53% of parent, the maximum application rate for IMCA was 0.0

amount if applied to 6 inches of water a concentration of 0.032 ppm ai was calculated. 

57 of 67
Table D2. Summary of terrestrial toxicity data submitted for flumiclorac-pentyl. 

Study Type Test Species TGAI or TEP 

Toxicity Endpoint 

(95% C.I.) 

(Measured/ 

Nominal)/ 

Slope 

Effect 

MRID (Year) 

Classification, 

DER date or 

source 

870.11 

Acute Oral 

Rat TGAI LD50 > 5000 mg/kg Mortality 42169812 

U.S. EPA 2005d 

870.11 

Acute Oral 

Rat TEP LD50 = 4100 mg/kg male 

LD50 = 3200 mg/kg female LD50 = 3600 mg/kg both 

Mortality 42169813 

U.S. EPA 2005d 

870.3100 

Subchronic Oral 

(90 day oral) 

Rat TGAI NOAEL = > 1359/1574 

mg/kg/day (M/F) 

LOAEL= not identified 

42169823, 

42310801 

(1990) 

Acceptable 

U.S. EPA 2005d 

870.4300 

Chronic/Carcinog

-enicity Toxicity 

Rat TGAI NOAEL = > 744.9/919.4 mg/kg/day (M/F) 

LOAEL = not identified 

No evidence of carcinogenicity 

42883906 

(1992) 

Acceptable 

U.S. EPA 2005d 

870.4100b 

Chronic Toxicity 

Dog TGAI NOAEL = 100 mg/kg/day 

LOAEL = 1000 mg/kg/day 

Decreased body weight gain in male, 

increased clottingtime, increased globulin 

levels, increased alpha-2 fraction of the 

serum protein electrophoresis in females 

42825817 

(1992) 

Acceptable 

U.S. EPA 2005d 

870.3800 

Reproduction and 

Fertility Effects 

Rat TGAI NOAEL= 16/18 mg/kg/day (M/F) 

LOAEL=781/925 mg/kg/day (M/F) 

Increased kidney weight in males and 

females and nephropathy in males 

42169835 

(1991) 

Acceptable 

U.S. EPA 2005d 

58 of 67
Study Type Test Species TGAI or TEP 

Toxicity Endpoint 

(95% C.I.) 

(Measured/ 

Nominal)/ 

Slope 

Effect 

MRID (Year) 

Classification, 

DER date or 

source 

Avian

850.2100 

Acute Oral 

Bobwhite Quail 

(Colinus 

virginianus) 

Age=16 wks. 

Bw= 170-186 g 

TGAI 

94.7 

LD50 > 2250 mg/kg-bw 

(nominal) (2131 mg 

ai/kg-bw) 

None observed 42169802 

(1990) 

Acceptable 

DER 4/28/92 

10 birds (

treatment. N

Group we

ind

850.2200 

Acute Dietary 

Bobwhite Quail 

(Colinus 

virginianus) 

Age = 10 days 

TGAI 

94.7 

8-day LC50 > 5620 

mg/kg-diet (nominal) 

(5322 mg ai/kg-diet) 

NOAEC = 5620 mg/kgdiet 

None observed 42169803 

(1991) 

Acceptable 

10 birds 

Measured 

prepared d

101% of n

instead o

Necropsies 

less than 

temperatur

greater th

850.2200 

Acute Dietary 

Mallard Duck 

(Anas 

platyrhynchos) 

Age = 10 day 

TGAI 

94.7 

8-day LC50 > 5620 

mg/kg-diet (nominal) 

(5322 mg ai/kg-diet) 

NOAEC = 5620 mg/kgdiet 

None observed 42169804 

(1991) 

Acceptable 

DER 4/28/92 

10 birds 

Measured 

prepared d

101% of n

instead o

Necrop

Temperatur

lower tha

850.2300 

Reproductive 

Bobwhite Quail 

(Colinus 

virginianus) 

Age = 32 wks 

TGAI 

94.6 

1-generation NOAEC = 

439 mg ai/kg-diet 

(measured) (highest test 

concentration tested) 

No mortality or 

reproductive 

effects attributed 

to treatment 

42825805 

(1992) 

Acceptable 

DER 2/4/94 

16 pens with 

Two mortal

two lowest g

incidental b

stored 

recommende

37.5°C and 

recommend

hours of light 

for first 

59 of 67
Study Type Test Species TGAI or TEP 

Toxicity Endpoint 

(95% C.I.) 

(Measured/ 

Nominal)/ 

Slope 

Effect 

MRID (Year) 

Classification, 

DER date or 

source 

Reproductive Mallard Duck 

(Anas 

platyrhynchos) 

Age = 17 wks 

TGAI 

94.7 

1-generation 

NOAEC= 220 mg ai/kgdiet (measured) 

LOAEC = 432 mg ai/kgdiet 

Decrease in egg 

laying and 

regressed ovaries 

and testes 

42825806 

(1992) 

Acceptable 

DER 1/19/94 

16 pens with 

One morta

believed to 

necropsies

instead of re

were set at 3

instead of 

70%. Eigh

instead of se

of study. 

included wh

effe

Terrestrial Invertebrates

850.3020 

Acute Contact 

Honey Bee 

(Apis mellifera 

L.) 

TGAI 

94.7 

LD50 > 106 μg/bee No treatment 

related mortality 

42169841 

(1990) 

Acceptable 

DER 4/14/92 

Bees were ex

of flumiclor

with aceto

ranged from 

14% i

Terrestrial Plants 

850.4100 

122-1 

Seedling 

Emergence 

Cabbage, corn 

cucumber, 

lettuce, oat, 

onion, 

perennial 

ryegrass, 

soybean, 

tomato, turnip 

IMCA1

98.0 

EC25 > 0.046 lb ai/A 

NOAEC < 0.046 lb ai/A 

Growth 43258001 

(1994) 

Acceptable 

DER 10/24/94 

14-day study

nominal con

No trea

morphologic

in any tes

significant r

shoot len

compare

Redu

60 of 67
61 of 67

Study Type Test Species TGAI or TEP 

Toxicity Endpoint 

(95% C.I.) 

(Measured/ 

Nominal)/ 

Slope 

Effect 

MRID (Year) 

Classification, 

DER date or 

source 

850.4250 

123-1 

Vegetative Vigor 

Corn, oat, 

onion, 

perennial 

ryegrass, 

soybean, 

tomato, 

cucumber, 

lettuce, radish 

and cabbage 

TEP 

10.6 

EC25 = 0.0027 lb ai/A – 

lettuce(dicot, dry weight) 

EC25 = 0.0410 lb ai/A – 

onion (monocot,dry 

weight and height ) 

NOEC = 0.00031 lb ai/A 

tomato(dicot, 

phytotoxicity) 

NOEC = 0.040 lb ai/A 

Onion 

Growth 43347401 

(1994) 

Acceptable 

DER 10/24/94 

EPA toxan

provide EC

used to calcu

values report

statement si

phyt

1 Due to rapid degradation of flumiclorac-pentyl and major degradate IMCA being mobile in soils and possibly bioactive, study conduc

herbicide Resource is applied at 0.0806 lb ai/A and degradate IMCA is 53% of parent, the maximum application rate for IMCA was 0.0amount 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 ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460

MEMORANDUM 

SUBJECT: Request for Phototoxicity Study Protocol for Light-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 (LDPHs) are a growing class of weed control 

chemicals (see partial listing attached). They 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, protoporphyrin IX is a 

powerful generator of singlet oxygen which in plants causes lipid membrane peroxidation 

leading to a rapid loss of turgidity and foliar burns. LDPH exposure in mammals has been 

shown to result in excretion of porphyrins in urine (porphynuria) and feces, increased liver 

weight, elevated blood porphyrin levels, developmental abnormalities, and cancer. Humans with 

a hereditary protox disorder (variegate porphyria) which results in lowered protox activity 

exhibit many symptoms similar to LDPH exposure in addition to photosensitivity. However, 

photosensitivity is not a commonly reported symptom of LDPH exposure in animals. 

An LDPH-induced occurrence of phototoxicity in rats6 and increased cytotoxicity to human skin 

cells grown in culture in the presence of light and an LDPH7

 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 LDPHs 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) recommends that phototoxicity studies be conducted on 

herbicides with this mode of action to determine if animals exposed to LDPHs and intense light 

(similar to sunlight) show increased toxicity relative to controls exposed 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 risk than guideline toxicity studies suggest. 

The ABTT is requesting that a LDPH phototoxicity 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 aquatic 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 radiation 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, American 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 Materials. 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.

 63 of 67
The ABTT requests that the study adequately address the following issues and suggests the 

paper, "Photoenhanced Toxicity of a Carbamate Insecticide to Early Life Stage Anuran 

Amphibians",5

 and other studies in the peer-reviewed scientific literature serve as sources of 

additional guidance: 

Species 

The fathead minnow may be an appropriate test species 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 accumulation, however, a life-cycle is not necessary 

to identify a phototoxic effect. 

Dosing

A range finding study should be conducted under defined low light conditions to identify an 

LC50 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 measurements 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 that will vary in different regions and seasons as 

well as with weather. If artificial light is used, the light should resemble 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 recommendation for an artificial light source. 

Dark, light, and positive controls

As this study is intended to identify potential effects of light on LDPH toxicity, an appropriate 

study protocol should include a dark, or low light, control group. Another group not exposed to 

chemicals but exposed to full light should be included (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 chambers 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. 

 64 of 67
 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