1 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

October 27, 2014 

PC Code: 109601 

MEMORANDUM DP Barcode: 421174 

SUBJECT: EFED Registration Review Problem Formulation for Dikegulac-sodium 

FROM: Elyssa Arnold, Biologist 

Greg Orrick, Environmental Scientist 

 Environmental Risk Branch 2 

Environmental Fate and Effects Division (7507P) 

REVIEWED Christine Hartless, Ph.D., Wildlife Biologist

BY: R. David Jones, Ph.D., Senior Agronomist 

 Jean Holmes, DVM, MPH, Risk Assessment Process Leader 

Environmental Risk Branch 2 

Environmental Fate and Effects Division (7507P) 

THROUGH: Brian Anderson, Branch Chief 

Environmental Risk Branch 2 

 Environmental Fate and Effects Division (7507P) 

 

TO: Matthew Manupella, Chemical Review Manager 

 Cathryn Britton, Team Leader 

 Kevin Costello, Branch Chief 

Risk Management and Implementation Branch 2 

Pesticide Re-evaluation Division (7508P) 

 

2014.10.27 

12:24:05 -04'00'

Date: 2014.10.27 

12:28:55 -04'00'

2014.10.28 

11:50:48 -04'00'

ROBERT JONES 

2014.10.28 12:56:37 -04'00'

Holmes, Jean 

2014.10.28 14:42:00 

-04'00'

Anderson, Brian 

2014.10.28 15:59:03 

-04'00'
2 



1. Executive summary ................................................................................................................. 3

2. Introduction ............................................................................................................................. 4

a. Mode of Action .................................................................................................................... 4

3. Use Characterization ............................................................................................................... 4

4. Conclusions from Previous Risk Assessments ....................................................................... 5

a. Ecological Risk Assessment ................................................................................................ 5

b. Drinking Water Exposure Assessments ............................................................................... 7

c. Clean Water Act Programs .................................................................................................. 7

5. Environmental Fate and Transport.......................................................................................... 8

a. Transformation Products ...................................................................................................... 9

6. Receptors............................................................................................................................... 12

a. Effects to Aquatic Organisms ............................................................................................ 13

b. Effects to Terrestrial Organisms ........................................................................................ 14

c. Ecological Incidents ........................................................................................................... 14

7. Exposure Pathways of Concern ............................................................................................ 15

8. Analysis Plan ........................................................................................................................ 15

a. Stressors of Concern .......................................................................................................... 15

b. Measures of Exposure ........................................................................................................ 16

c. Measures of Effect ............................................................................................................. 16

d. Endangered Species Assessments ...................................................................................... 16

e. Endocrine Disruptor Screening Program ........................................................................... 16

9. Preliminary Identification of Data Gaps ............................................................................... 17

a. Environmental Fate ............................................................................................................ 17

b. Effects ................................................................................................................................ 18

10. References .......................................................................................................................... 23

a. Submitted Environmental Fate Studies .............................................................................. 24

b. Submitted Ecological Toxicity Studies .............................................................................. 24

Appendix A. Dikegulac-sodium Ecotoxicity Data ....................................................................... 27
3 

1. Executive summary 

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem 

formulation for the ecological risk, environmental fate, endangered species, and drinking water 

assessments to be conducted as part of the registration review of dikegulac-sodium. 

The problem formulation describes the methods planned to be used during the completion of 

drinking water and ecological risk assessments in support of registration review and provides an 

overview of the environmental fate, ecological effects, potential risks associated with the use, 

and uncertainties unique to the risk assessment of dikegulac-sodium. This document also 

identifies additional studies that would be beneficial to the conduct of an ecological risk 

assessment. 

The dikegulac-sodium Reregistration Eligibility Decision (RED) was completed in 2007. Since 

that time, there have been no substantial changes to the registration or use patterns of dikegulacsodium. The RED concluded that there is risk of adverse effects to terrestrial plants and 

organisms that depend on them for survival, growth, or reproduction at or near its application 

site. The conclusions from the RED remain unchanged, and an updated, full ecological risk 

assessment is not needed for registration review. EFED recommends that additional data be 

requested to allow for a more comprehensive evaluation of potential effects to honey bees, 

consistent with Guidance for Assessing Pesticide Risks to Bees (USEPA et al., 2014). EFED will 

evaluate those data when they are submitted and will work with Pesticide Re-evaluation Division 

(PRD) to address any risks of concern identified by those data. 

The following are the needed data and uncertainties for dikegulac-sodium: 

Data Needs 

x Fate Data 

o None 

x Ecotoxicity Data 

o Non-guideline: Honey bee acute oral toxicity 

o Non-guideline: Honey bee acute and chronic larval toxicity 

o Non-guideline: Honey bee adult chronic 10-day toxicity 

Some data gaps are not identified as data needs at this time (see Section 9 for details) due to the 

limited use patterns and low overall usage of dikegulac-sodium in the United States. If usage of 

dikegulac-sodium significantly increases in the future, data needs for risk assessment may also 

change. 

Other Major Uncertainties 

x Some label directions are ambiguous. The maximum single application rate for 

ornamental olive, glossy privet, multiflora rose, and Japanese holly is not stated on pages 

8-9 of EPA Reg. No. 2217-776. The reapplication interval for greenhouse and nursery 

ornamentals is not stated on page 11 of EPA Reg. No. 2217-776. The maximum 
4 

application rate of 11 lbs a.i./acre on EPA Reg. No. 2217-932 might be underestimated 

because the label says “large plants may require higher spray volumes” (p. 4). 

2. Introduction 

Dikegulac-sodium is a plant growth regulator that was first registered in 1978. It is used on 

ornamentals, nursery crops, and trees to reduce growth, flowering, and/or fruit set. Three end-use 

formulations containing dikegulac-sodium are currently registered for use in the United States. 

Dikegulac-sodium was previously assessed at the time of the Reregistration Eligibility Decision 

(RED) in 2006 (USEPA, 2006b). 

a. Mode of Action 

Dikegulac-sodium interferes with terminal growth areas in plants by inhibiting DNA synthesis 

which is required for new growth. Thus, the dominant growth points (apexes) of treated plants 

are suppressed, resulting in the breaking of “apical dominance” and the enhancing of the growth 

of lateral shoots. 

3. Use Characterization 

Dikegulac-sodium is applied as a foliar spray, soil drench, tree trunk injection, or tree trunk spray 

band. It is used on ornamentals, nursery crops, and trees to reduce growth, flowering, and/or fruit 

set. Three end-use formulations containing 18.5% dikegulac-sodium are currently registered for 

use in the United States: Atrinal Plant Growth Regulator SC (EPA Reg. No. 2217-776), Atrinal 

Nursery and Greenhouse EC (EPA Reg. No. 2217-932), and Pinscher PGR Solution RTU (EPA 

Reg. No. 69117-7). There is no technical registration in the United States. 

Table 1 lists the maximum use patterns for the labeled use sites. Some label directions are 

ambiguous. The maximum single application rate for ornamental olive, glossy privet, multiflora 

rose, and Japanese holly is not stated on pages 8-9 of EPA Reg. No. 2217-776. The reapplication 

interval for greenhouse and nursery ornamentals is not stated on page 11 of EPA Reg. No. 2217-

776. The maximum application rate of 11 lbs a.i./acre on EPA Reg. No. 2217-932 might be 

underestimated because the label says “large plants may require higher spray volumes” (p. 4). 
5 

Table 1. Maximum Use Patterns for Current Uses of Dikegulac-sodium 

EPA

Reg. No. Use 

Max. Single 

App. Rate 

(lbs a.i./A) 

Max. Annual 

App. Rate 

(lbs a.i./A) 

App. 

Interval 

(d) 

App. Type Additional App. 

Directions 

2217-932 

Greenhouses, lathhouses, 

shadehouses, nurseries (field 

and containerized), tree farms 

1.4 - 11+ A 22+ B 14 

Foliar spray Use with medium 

or coarser spray 

nozzles. 

Do not apply 

through any type 

of irrigation 

system. 2217-776 

Greenhouse and nursery 

ornamentals 0.36 - 5.7 C 11 D Not stated

Landscape ornamentals 

(shrubs, hedges, 

groundcovers, trees) 

1.4 – 4.3 E 8.5 B 14 

0.04 lbs a.i./ 

12” tree DBH F

0.04 lbs a.i./ 

12” tree DBH

Not 

applicable

Bark band, 

soil drench G

Ornamental olive, glossy 

privet, multiflora rose, 

Japanese holly 

Not stated 1 app./yr Foliar spray 

Broadleaf trees in rights-ofway, parks, other areas 0.09 lbs a.i./ 

16” tree DBH F

0.09 lbs a.i./ 

16” tree DBH

Tree 

injection (none reported 

here) 69117-7 Ornamental trees 0.0016 lbs a.i./ 

30” tree CBH H

0.0032 lbs a.i./ 

30” tree CBH

4 - 6 

months 

Tree 

injection 

A The application rate varies by treated plant species. The rate of 11 lbs a.i./A reflects use of 4 fl oz product per 

spray gallon applied at the rate of 2 quarts of spray per 100 sq ft. The label statement “large plants may require 

higher spray volumes” (p. 4) allows for application rates greater than 11 lbs a.i./A in some cases. 

B Two applications are allowed per year for plants with long growing seasons (p. 4). 

C The application rate varies by treated plant species. The rate of 5.7 lbs a.i./A reflects use of 4 fl oz product per 

spray gallon applied at the rate of 1 gallon of spray per 400 sq ft. 

D The label states “most plants should be treated only once per year,” (p. 11) allowing for two applications to some 

plants. 

E The application rate varies by treated plant species. The rate of 4.3 lbs a.i./A reflects use of 3 fl oz product per 

spray gallon applied at the rate of 1 gallon of spray per 400 sq ft. The label allows for higher spray volumes for 

trees (p. 4), which allows for application rates greater than 4.3 lbs a.i./A for landscapes with trees. 

F “DBH” is the diameter of the tree trunk(s) at breast height. 

G Bark bands are applied with compressed air sprayers, backpack sprayers and other pressurized sprayers at low 

pressure settings. Soil drenches are applied with “equipment capable of delivering the drench mixture uniformly 

around the base of the plant” and “all root flares.” 

H “CBH” is the circumference of the tree trunk(s) at breast height. 

Public usage data were not located. PBI/Gordon Corp. indicated that typical foliar spray 

application rates are 3-4 lbs a.i./acre, with one application per year (Focus meeting, Jul. 24, 

2014). 

4. Conclusions from Previous Risk Assessments 

a. Ecological Risk Assessment 

The only full ecological risk assessment previously conducted for dikegulac-sodium was 

completed for the Reregistration Eligibility Decision (RED) in 2006 (USEPA, 2006b). The RED 

assessment concluded that registered uses of dikegulac-sodium had the potential for direct 

adverse effects on listed and non-listed terrestrial plants. While there were no acute risk concerns 

identified for freshwater aquatic organisms, mammals, birds or reptiles, the lack of chronic 

toxicity data for birds, fish, and aquatic invertebrates precluded the ability to identify or exclude 
6 

chronic risks for these taxa. A summary of exceedances of the level of concern (LOC) is listed in 

Table 2. Figure 1 and Table 3 summarize the potential risks and the supporting evidence. 

Aquatic exposure was modeled in the RED using GENEEC. Two applications of 5.68 lb ae/A 

with a 10 day application interval were modeled. The resulting estimated exposure 

concentrations (EEC) for the 1-in-10-year peak, 21-day mean, and 60-day mean measures were 

663, 663, and 662 ppb ae, respectively. 

Table 2. LOC Exceedances for Recently Assessed Proposed Uses 

Effect

Taxonomic Group 

Birds1 Mammals Terrestrial 

Plants 

Terrestrial 

Inverts Fish1 Aquatic Inverts1

Aquatic 

Plants 

Direct Effect LOC 

Exceedance -- --  -- -- -- -- 

Indirect Effect 

Potential       

1

 Risk conclusions reflect acute exposure only. No chronic toxicity data were available with which to assess chronic 

risk to birds, fish, or aquatic invertebrates. 

Figure 1. Graphic Summary of Potential Risks of Current Uses 
7 

Table 3. Evidence of Risk to Taxonomic Groups from Dikegulac-sodium Uses 

Predominant Evidence of Negligible Risk Predominant Evidence of Risk 

Aquatic Plants: All RQs <LOC for listed and non-listed 

species. 

Terrestrial Plants: RQs > LOC (up to 2.3) for semiaquatic areas only. 

Mammals: No toxicity observed in acute studies. 

Chronic RQs <1.0. 

Limited Evidence of Negligible Risk Limited Evidence of Risk 

Fish & Aquatic Invertebrates: No toxicity observed in 

acute studies with multiple species. Chronic risk is 

unlikely; toxicity would have to be 1,000 to 10,000 

times greater than acute toxicity to trigger risk concerns.

Terrestrial Invertebrates: Risk is presumed in the 

absence of acute and chronic oral toxicity data for adults 

and larvae. Dikegulac is systemic in plants so exposure 

via pollen and nectar are possible. 

Birds: No toxicity observed in acute studies; no chronic 

toxicity data are available but exposure potential is low 

due to the limited use pattern 

b. Drinking Water Exposure Assessments 

The only drinking water exposure assessment previously conducted for dikegulac-sodium was 

completed for the Reregistration Eligibility Decision (RED) in 2007 (USEPA, 2007a). Maximum 

screening exposure estimates for the residues of concern were 950 μg/L (1-in-10-year peak) and 

240 μg/L (1-in-10-year annual mean) for surface water and 4.8 μg/L for ground water. 

Significant uncertainty was associated with these values as a result of limited environmental fate 

data and low annual production values. Actual drinking water exposure was expected to be 

negligible. 

c. Clean Water Act Programs 

The Clean Water Act requires the Agency to publish water quality criteria that accurately reflect 

the latest scientific knowledge on the kind and extent of all identifiable effects on health and 

welfare that might be expected from the presence of pollutants in any body of water, including 

ground water. While these recommended criteria do not, in themselves, impose any 

requirements, states and authorized tribes can use them to develop water quality standards. An 

Aquatic Life Ambient Water Quality Criteria document has not been published for dikegulacsodium (see url: http://www.epa.gov/waterscience/criteria/). 

The Office of Pesticide Programs (OPP) publishes aquatic life benchmarks for freshwater species 

based on toxicity values for the most sensitive species from the most recent risk assessments. 

However, aquatic life benchmarks have not been published for dikegulac-sodium (see url: 

http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm#benchmarks). Any data 

submitted or otherwise located as part of the registration review process may be used to update 

aquatic life benchmarks if applicable. 

Dikegulac-sodium 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. No Total Maximum Daily Load (TMDL) criteria have been developed for dikegulac-sodium, 

based on information provided at 
8 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id

=885&p_pollutant_group_name=PESTICIDES. 

5. Environmental Fate and Transport 

As a sodium salt, dikegulac-sodium will immediately dissociate into dikegulac acid and sodium 

ions in water (dikegulac-sodium and its acid are collectively referred to as dikegulac). Thus, 

dikegulac acid is the form that aquatic organisms will be exposed to. The compound is relatively 

nonvolatile, hydrophilic, and highly mobile in soil. As a hydrophilic compound, dikegulac will 

not bioaccumulate. Dikegulac (sodium salt plus free acid) biodegrades in soil with a half-life of 

16 days and undergoes abiotic hydrolysis only in acidic conditions. The limited set of chemical 

properties and environmental fate data for dikegulac are listed in Table 4. (The test compound in 

each study was dikegulac-sodium. But the parameters represent total dikegulac due to the 

immediate dissociation of the sodium salt in water.) 

Dikegulac and degradates are not expected to move to ground water due to their rate of 

biodegradation. However, these compounds may move to surface water bodies via spray drift 

and runoff of dissolved residues. 

Table 4. Chemical Properties and Environmental Fate Parameters of Dikegulac A

Parameter Value Source

Selected Physical/Chemical Parameters 

Molecular mass (molecular formula) 296.25 g/mol (C12H17O7Na) (Calculated) 

Vapor pressure (25 °C) 3.1 x 10-12 torr Neely and Blau, 

1985 * 

Aqueous solubility (20qC) 5.9 × 105

 mg/L Budavari et al., 

1996 * 

Henry’s Law Constant (25°C) 2.1 x10-18 atm-m3/mol (Calculated) 

Log octanol-to-water partition coefficient 

(log KOW) 

-2.05 Meylan and 

Howard, 1995 * 

Dissociation constants (pKa) Not determined None * 

Persistence in Water

Hydrolysis half-life (25qC) pH 5: 5.3 d pH 6: 40 d 

pH 7: stable pH 9: stable 

MRID 46932401 

Persistence in Soil 

Aerobic soil metabolism half-life (25°C, pH 6.6) 16 d (ND sandy loam) MRID 46932402 

Mobility

Freundlich organic carbon-normalized 

coefficients (KFOC) 

2.5, 4.9, 6.2, 6.7 L/kgOC MRID 46939501 

Field Dissipation / Fish Bioconcentration 

(no acceptable data) A The test compound in each study was dikegulac-sodium. But the parameters represent total dikegulac due to the 

immediate dissociation of the sodium salt in water.

* The asterisked dikegulac-sodium product chemistry studies were waived. Cited sources are from USEPA, 2006a. 
9 

a. Transformation Products 

Dikegulac-sodium immediately dissociates into dikegulac acid and sodium ions in water. Major 

degradates of dikegulac acid include monoacetyl dikegulac (MA; forming up to 30% of the 

applied after 21 days in soil), an acid conjugate of monoacetyl dikegulac (M5; forming up to 

37% of the applied after 60 days in soil), and carbon dioxide (forming 39% of the applied after 

276 days in soil). Chemical names and structures of dikegulac and its degradates are in Table 5. 

Environmental fate studies on the degradates of dikegulac were not located.
10 

Table 5. Dikegulac-sodium and Its Environmental Transformation Products A

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type MRID Maximum%AR (day)

Final %AR 

(study length)

PARENT

Dikegulacsodium

IUPAC: Sodium 2,3:4,6-di-Oisopropylidene-Į-L-xylo-2-

hexulofuranosonate 

CAS: Sodium 2,3:4,6-bis-O-(1-

methylethylidene)-Į-L-xylo-2-

hexulofuranosonate 

CAS No.: 52508-35-7 

Formula: C12H17O7Na 

MW: 296.25 g/mol 

SMILES:

O=C(O[Na])C(OC(O1)(C)C)(OC(C2OC(O

3)(C)C)C3)C12 

Dikegulac acid 

Diacetonate of 

2-keto-Lgulonic acid 

IUPAC: 2,3:4,6-di-O-isopropylidene-Į-Lxylo-2-hexulofuranosonic acid 

CAS: 2,3:4,6-bis-O-(1-methylethylidene)-

Į-L-xylo-2-hexulofuranosonic acid 

CAS No.: 18467-77-1 

Formula: C12H18O7

MW: 274.27 g/mol 

SMILES:

O=C(O)C(OC(O1)(C)C)(OC(C2OC(O3)(C

)C)C3)C12 

O

O

O O

O

CH3 C3 H

O

O

CH3 C3 H

Na

O

O

O O

O

CH3 C3 H

O

OH

CH3 C3 H
11 

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type MRID Maximum%AR (day)

Final %AR 

(study length)

TRANSFORMATION PRODUCTS

Monoacetyl

dikegulac

MA

2,3-o-isopropylidene-2-keto-L-gulonic acid

Formula: C10H16O7

MW: 248.23 g/mol 

Hydrolysis –pH 5 

Hydrolysis –pH 6 

Hydrolysis –pH 7 

Hydrolysis –pH 9 

46932401

97% (30 d) 

45% (30 d) 

14% (30 d) 

12% (0 d) 

97% (30 d) 

45% (30 d) 

14% (30 d) 

9.6% (30 d) 

Aerobic soil 46932402 30% (21 d) n.d. (276 d) 

M5 Not reported (acid conjugate of MA) 

Aerobic soil 46932402 37% (60 d) 1.5% (276 d) 

2-keto 2-keto-L-gulonic acid 

Formula: C6H10O7

MW: 194.14 g/mol 

Hydrolysis –pH 5 

Hydrolysis –pH 6 

Hydrolysis –pH 7 

Hydrolysis –pH 9 

46932401

3.1% (21 d) 

2.4% (4 hr) 

1.3% (1 d) 

1.5% (30 d) 

2.9% (30 d) 

2.0% (30 d) 

n.d. (30 d) 

1.5% (30 d) 

Aerobic soil 46932402 7.0% (190 d) 6.8% (276 d) 

Unextracted 

residues 

Not applicable 

Not applicable Aerobic soil 46932402 21% (120 d) 20% (276 d) 

Carbon dioxide Carbon dioxide 

Formula: CO2

MW: 44.1 g/mol 

O O

Hydrolysis 46932401 n.a. 

Aerobic soil 46932402 39% (276 d) 39% (276 d) 

A n.a. means “not analyzed.” n.d. means “not detected.”

O

O

O O

HO O

OH

CH3 C3 H

O

OH

O O

HO O

OH

CH3 C3 H

O

OH

OH HO

O

OH

O

OH
12 

6. Receptors 

The toxicity endpoints that would be used in risk assessment for aquatic and terrestrial organisms 

exposed to dikegulac-sodium are presented in Table 6 and Table 7 below. A complete list of the 

ecotoxicity data available for dikegulac-sodium can be found in Appendix A. The toxicity 

endpoints are presented in units of acid equivalents (ae) of dikegulac.

Dikegulac-sodium is practically non-toxic on an acute basis to all animals tested, including 

freshwater fish, freshwater aquatic invertebrates, estuarine/marine aquatic invertebrates, birds, 

mammals, and terrestrial invertebrates. No mortality was observed in any of the acute toxicity 

studies with the exception of the brown shrimp. No acute toxicity data are available for 

estuarine/marine fish. Toxicity to terrestrial invertebrates has been assessed only for adult honey 

bees via an acute contact exposure. 

No chronic toxicity data for dikegulac-sodium are available for birds, fish, or aquatic 

invertebrates. For mammals, no multi-generation reproductive studies have been submitted to the 

Agency, but developmental toxicity studies are available. A developmental toxicity study on 

rabbits (MRID 43064618) was conducted with oral exposures of 0, 200, 700, and 2000 mg 

a.i./kg-bw/day. At 2000 mg a.i./kg-bw, there was a 92% decrease in maternal weight gain during 

dosing compared to the control and diarrhea was observed. No fetal parameters including litter 

size, litter weight or viability were affected. 

Aquatic plant toxicity data demonstrate that dikegulac-sodium is moderately toxic to vascular 

aquatic plants and much less toxic to non-vascular aquatic plants. Toxicity to terrestrial plants is 

evident, as expected based on the mode of action. There is no difference in sensitivity of 

monocots versus dicots due to the mode of action. Therefore, the most sensitive species was 

chosen from each study to represent both monocots and dicots. Plant height was the most 

sensitive endpoint in both the seedling emergence and vegetative vigor studies. The vegetative 

vigor study represented a more sensitive exposure route, with toxicity endpoints approximately 

ten times lower than those from the seedling emergence study. 
13 

a. Effects to Aquatic Organisms 

Table 6. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for 

Dikegulac-sodium

Taxonomic

Group 

Study 

Type 

Surrogate Species Toxicity Value 

(mg/L measured ae) 

Acute Toxicity 

Classification 

MRID 

(Study Classification)

Freshwater fish 

& Aquatic-phase 

amphibians 

Acute Rainbow trout1

(Oncorhynchus mykiss) 

96-h LC50 >121 Practically 

nontoxic 

46547301 

(Acceptable) 

Freshwater 

invertebrates 

Acute Daphnia magna2 96-h EC50 >10,000 Practically 

nontoxic

45631702 

(Supplemental3

) 

Marine/estuarine 

invertebrates 

Acute Brown shrimp 

(Crangon crangon) 

48-h EC50 = 8,783 Practically 

nontoxic

45631702 

(Supplemental3

) 

Aquatic plants Vascular Duckweed (Lemna 

gibba) 

7-d EC50 = 9.6 

NOAEC = 3.5 

Moderately 

toxic 

46547307 

(Supplemental4

) 

Nonvascular Green algae 

(Pseudokirchneriella 

subcapita) 

96-h EC50 = 100 

NOAEC = 27 

Practically 

nontoxic

46547308 

(Acceptable) 

Blue-green algae 

(Anabaena flos-aquae)

96-h EC50 > 120 

NOAEC = 15 

Practically 

nontoxic

46547309 

(Acceptable) 

Freshwater diatom 

(Navicula pelliculosa) 

96-h EC50 >112 

NOAEC = 112 

Practically 

nontoxic

46547310 

(Acceptable) 

Marine diatom 

(Skeletonema costatum)

96-h EC50 > 106 

NOAEC = 26 

Practically 

nontoxic

46547311 

(Supplemental5) 

NA: Not Applicable 

1 No mortality or clinical signs of toxicity were observed. Additional acceptable acute toxicity studies showed no 

mortality or clinical signs of toxicity in the rainbow trout (MRID 00059584) or bluegill sunfish (Lepomis 

macrochirus) (MRID 00059583) up to 10,000 mg/L ae. 2 No mortality was observed. Daphnids showed signs of stress at the highest concentration tested (10,000 ppm). 3

 Static test with no measured concentrations. Purity not reported. 4

 Study classified as supplemental because it was a static test. 

5

 Study classified as supplemental because initial cell density was 77,000 cells/ml. OCSPP guideline 850.4500 

recommends an initial density of 10,000 cells/ml. 
14 

b. Effects to Terrestrial Organisms 

Table 7. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for 

Dikegulac-sodium

Taxonomic

Group 

Study Type Species Toxicity Value 

(measured ae) 

Acute 

Toxicity 

Classification 

MRID 

(Study 

Classification) 

Birds, 

Reptiles, & 

Terrestrialphase 

amphibians 

Acute Bobwhite quail 

(Colinus 

virginianus) 

LD50 >2083 mg/kgbw1

Practically 

nontoxic

46547302 

(Acceptable) 

Sub-acute 

dietary 

Bobwhite quail LC50 >5460 mg/kgdiet1Practically 

nontoxic

46547303 

(Acceptable) 

Mammals Acute oral Laboratory rat 

(Rattus 

norvegicus) 

LD50 >4,612 mg/kgbw (M&F)2,3

Practically 

nontoxic

44093901 

(Acceptable) 

Acute 

inhalation 

Laboratory rat LC50 > 2.09 mg/L4 Toxicity 

category IV 

44093903 

(Acceptable) 

Developmental Rabbit NOAEL = 646 

LOAEL = 1845 

mg/kg-bw2,5

NA 43064618 

(Acceptable) 

Terrestrial 

invertebrates 

Acute contact Honey bee (Apis

mellifera) 

LD50 > 81 ug/bee4 Practically 

nontoxic

44093910 

(Acceptable) 

Terrestrial 

plants 

Seedling 

Emergence 

Radish (Raphanus 

sativus) 

EC25 = 3.2 lbs/A 

NOAEC = 1.2 lbs/A 

NA 46547305 

(Acceptable) 

Vegetative 

Vigor 

Bean (Phaseolus 

vulgaris) 

EC25 = 0.61 lbs/A 

NOAEC = 0.20 

lbs/A 

NA 46547306 

(Acceptable) 

NA: Not Applicable 

1

 No observed mortality, treatment-related clinical signs of toxicity or effects on food consumption or body weight. 2

 Nominal concentrations, no measured concentrations available. 

3

 No mortality was observed. Increased activity was observed in one female on day 2 following dosing and staining 

around the mouth was observed in one female on day 0. No treatment-related effect on body weight was observed 

during the study, and no significant findings were observed upon necropsy. 4

 No mortality was observed. 

5

 Endpoints affected: maternal weight gain (92% decrease compared to controls) and diarrhea. No fetal parameters 

including litter size, litter weight or viability were affected. Concentrations tested: 0, 184, 646, 1845 mg ae/kg/day. 

c. Ecological Incidents 

The ecological incident information system (EIIS) is an OPP database that houses ecological 

incidents that have been reported to the Agency. When available, EIIS includes date and location 

of an incident, type and magnitude of effects observed in various species, use(s) of pesticides 

known or suspected of contributing to the incident, and results of any chemical residue analysis 

or other analyses conducted during incident investigation. EIIS incidents are categorized 

according to the certainty that the incident resulted from pesticide exposure. The Avian 

Monitoring System (AIMS) is a database administered by the American Bird Conservancy that 

contains publicly available data on reported avian incidents involving pesticides. Many of the 

incidents listed in this database are also in the EIIS. 

As of July 7, 2014, there were no ecological incidents reported in EIIS or AIMS for dikegulacsodium. There were also no minor incidents reported in aggregate incident reports. An absence 
15 

of reports does not necessarily equate to an absence of incidents given the nature of incident 

reporting. 

7. Exposure Pathways of Concern 

The environmental fate properties and use patterns of dikegulac-sodium indicate that direct 

spray, spray drift, and runoff represent potential transport mechanisms to aquatic and terrestrial 

organisms. However, use patterns of dikegulac-sodium are limited and overall usage is low and 

spread across a broad geographic area, according to confidential sales data provided to EPA by 

the registrants (Focus meeting, Jul. 24, 2014). Therefore, exposure in both aquatic and terrestrial 

environments is expected to be limited. 

Drinking water and inhalation exposure pathways are typically considered using the SIP 

(Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening 

methods. However, due to the non-definitive acute toxicity endpoints for mammals and birds and 

the lack of chronic toxicity data for birds, quantitative use of these tools is not appropriate for 

dikegulac-sodium. Based on the use patterns, usage data, and lack of observed toxic effects in the 

available studies (see Section 6), exposure via inhalation and drinking water are not expected to 

be pathways of concern for either mammals or birds. SIP and STIR are described in detail at: 

http://www.epa.gov/oppefed1/models/terrestrial/index.htm. 

8. Analysis Plan 

The dikegulac-sodium RED was completed in 2006. Since that time, there have been no 

substantial changes to the registration or use patterns of dikegulac-sodium. The RED concluded 

that there is risk of adverse effects to terrestrial plants and organisms that depend on them for 

survival, growth, or reproduction at or near its application site. The conclusions from the RED 

remain unchanged, and an updated, full ecological risk assessment is not needed for registration 

review. EFED recommends that additional data be requested to allow for a more comprehensive 

evaluation of potential effects to honey bees. EFED will evaluate those data when they are 

submitted and will work with PRD to address any risks of concern identified by those data. 

a. Stressors of Concern 

i. Ecological Risk Assessment 

Dikegulac-sodium, its free acid, MA, and M5 are the residues of concern for terrestrial and 

aquatic organisms. Due to structural similarity and lack of toxicity data, the residues of concern 

are assumed to have equivalent toxicity. 

ii. Drinking Water

There are no stressors of concern for the human health risk assessment of dikegulac-sodium. The 

Health Effects Division (HED) did not find any toxicity effects that warranted selection of 

endpoints [email from Donna Davis (HED) to Greg Orrick (EFED) and 15 other recipients, dated 
16 

Jul. 31, 2014]. Therefore, a quantitative human health risk assessment and an associated drinking 

water exposure assessment will not be conducted for Registration Review. 

b. Measures of Exposure 

If conducting an assessment, EFED would use standard available models to evaluate potential 

exposures to aquatic and terrestrial organisms as described at 

http://www.epa.gov/oppefed1/models/water/index.htm and 

http://www.epa.gov/pesticides/science/models_db.htm. GENEEC or the Surface Water 

Concentration Calculator (SWCC) are currently the model typically used to estimate aquatic 

exposure. T-REX, Bee-REX, and TerrPlant are currently models typically used to estimate 

terrestrial exposure. The limited use patterns of dikegulac-sodium and low usage in the United 

States would be taken into account when estimating exposure. If usage significantly increases, 

then this consideration would also change. 

i. Available Monitoring Data 

The Agency is not aware of monitoring conducted by federal and state agencies for dikegulac, as 

of Aug. 1, 2014. Monitoring would be considered in the assessment to the extent that data on 

dikegulac are available. 

c. Measures of Effect 

Toxicity data presented in Section 6 of this problem formulation would be used to calculate risk 

quotients. Any additional information submitted by the registrant or found in the open literature 

prior to conduct of the risk assessment would also be considered. The open literature studies are 

identified using EPA’s ECOTOXicology database (ECOTOX) (USEPA, 2007b), which employs 

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

and wildlife. The evaluation of both sources of data can also provide insight into the direct and 

indirect effects of pesticides on biotic communities from loss of species that are sensitive to the 

chemicals and from changes in structure and functional characteristics of the affected 

communities. 

d. Endangered Species Assessments 

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the 

Agency would evaluate risks to federally listed threatened and/or endangered (listed) species 

from registered uses of pesticides in registration review. The process for evaluating potential 

risks to listed species is further described at 

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

e. Endocrine Disruptor Screening Program 

Dikegulac-sodium was not included in the first group of 67 chemicals issued an order to conduct 

Tier 1 EDSP testing and is not on the second list of chemicals for Tier 1 screening. For 

additional information the EDSP program, visit http://www.epa.gov/endo/. 
17 

9. Preliminary Identification of Data Gaps 

a. Environmental Fate 

Table 8 identifies environmental fate studies by MRID that offer data for each guideline 

requirement, as well as study classifications and whether or not further data are needed in order 

to support risk assessment. Additional environmental fate studies and analytical methods are not 

needed due to the low risks from aquatic exposure. 

Table 8. Submitted Environmental Fate Data for Dikegulac-sodium 

OCSPP 

Guideline Data Requirement SubmittedStudies (MRID)

Study 

Classifications

Sufficient

for risk 

assessment?

Current Additional Data Need 

835.2120 Hydrolysis 56146 Pre-GLP * Yes None 

67144 Pre-GLP * 

46932401 Acceptable 

835.2240 Aqueous photolysis 49723 Pre-GLP * Yes None: dikegulac is not expected to 

photolyze 

835.2410 Soil photolysis (None) (Not 

applicable) 

Yes None: dikegulac is not expected to 

photolyze

835.4100 Aerobic soil 

metabolism 

46932402 Supplemental Yes None: a study of three additional 

soils is not needed due to the limited 

use pattern and low toxicity to 

aquatic organisms 

835.4200 Anaerobic soil 

metabolism 

(None) (Not 

applicable) 

Yes None 

835.4300 Aerobic aquatic 

metabolism 

(None) (Not 

applicable) 

Yes None: a study is not needed due to 

the limited use pattern and low 

toxicity to aquatic organisms 

835.4400 Anaerobic aquatic 

metabolism 

(None) (Not 

applicable) 

Yes None: a study is not needed due to 

the limited use pattern and low 

toxicity to aquatic organisms 

835.1230 

835.1240 

Adsorption/ 

desorption and 

leaching 

49725 Pre-GLP * Yes None 

46939501 Acceptable 

835.6100 Terrestrial field 

dissipation 

49727 Pre-GLP * Yes None: a study is not needed due to 

the limited use pattern and low 

toxicity to aquatic organisms 

56147 Pre-GLP * 

67149 Pre-GLP * 

850.1730 Fish 

bioconcentration 

(None) (Not 

applicable) 

Yes None: hydrophilic compounds do not 

bioaccumulate

850.6100 Analytical method 

in soil 

49724 Pre-GLP * Yes Analytical methods are not needed to 

address low risks. 

Analytical method 

in water 

(None) (Not 

applicable) 

* “Pre-GLP” means that the study predates the 40 CFR Part 160 regulations and is not likely to be acceptable 

according to current guideline standards. 
18 

b. Effects 

Table 9 and Table 10 identify ecological effects studies by MRID that offer data for each 

guideline requirement, as well as study classifications and whether or not further data are needed 

in order to support risk assessment. Rationale for the additional non-guideline data requested is 

presented below the tables. 

Table 9. Submitted Aquatic Ecological Effects Data for Dikegulac-sodium

OCSPP 

Guideline Data Requirement 

Submitted

Studies 

(MRID) 

Study 

Classifications 

Sufficient

for risk 

assessment? 

Current Additional Data 

Need1

850.1010 Freshwater 

invertebrate 

acute toxicity 

45631702 Supplemental Yes None

850.1025 

850.1035 

850.1045 

850.1055 

Saltwater 

invertebrate 

acute toxicity 

45631702 Supplemental Yes None

850.1075 Freshwater fish acute 

toxicity 

46547301 Acceptable Yes None

45631702 Supplemental 

00059584 Acceptable 

00059583 Acceptable 

00059586 Supplemental 

00059585 Invalid 

850.1075 Saltwater fish acute 

toxicity 

(None) (Not 

applicable) 

Yes None: EPA would use the 

estuarine/marine invertebrate 

data to represent all 

estuarine/marine taxa. 

850.1300 Freshwater 

invertebrate 

life cycle 

(None) (Not 

applicable) 

Yes None: chronic toxicity would 

need to be at least 10,000 times 

greater than the acute toxicity 

to freshwater invertebrates to 

trigger a risk concern. 

850.1350 Saltwater 

invertebrates 

life cycle 

(None) (Not 

applicable) 

Yes None: chronic toxicity would 

need to be at least 1,000 times 

greater than the acute toxicity 

to saltwater invertebrates to 

trigger a risk concern. 

850.1400 Freshwater fish 

early-life stage 

(None) (Not 

applicable) 

Yes None: chronic toxicity would 

need to be at least 10,000 times 

greater than the acute toxicity 

to freshwater fish to trigger a 

risk concern.
19 

OCSPP 

Guideline Data Requirement 

Submitted

Studies 

(MRID) 

Study 

Classifications 

Sufficient

for risk 

assessment? 

Current Additional Data 

Need1

850.1400 Saltwater fish 

early-life stage 

(None) (Not 

applicable) 

Yes None: chronic toxicity would 

need to be at least 1,000 times 

greater than the acute toxicity 

to saltwater invertebrates to 

trigger a risk concern.

850.1500 Fish life cycle (None) (Not 

applicable) 

Yes None: chronic toxicity would 

need to be at least 10,000 times 

greater than the acute toxicity 

to freshwater fish to trigger a 

risk concern.

850.1735 Whole sediment 10-d 

freshwater 

invertebrate 

(None) (Not 

applicable) 

Yes None: dikegulac-sodium is not 

expected to partition to 

sediment. 

850.1740 Whole sediment 10-d 

estuarine/marine 

invertebrate 

(None) (Not 

applicable) 

Yes None: dikegulac-sodium is not 

expected to partition to 

sediment. 

850.4400 Aquatic plant 

Toxicity Test using 

Lemna spp. 

46547307 Supplemental Yes None 

850.4500 Algal toxicity 46547308 Acceptable Yes None

46547310 Acceptable Yes None

46547311 Supplemental Yes None

850.4550 Cyanobacteria 46547309 Acceptable Yes None

1 Statements regarding the toxicity values required for risk to rise above levels of concern are based on EECs calculated 

for the RED (see Section 4). 

Table 10. Submitted Terrestrial Ecological Effects Data for Dikegulac-sodium

OCSPP 

Guideline Data Requirement 

Submitted

Studies 

(MRID) 

Study 

Classifications 

Sufficient

for risk 

assessment? 

Current Additional Data 

Need

850.2100 Avian oral toxicity 46547302 Acceptable Yes None: no data are available for 

a passerine species, however 

because no mortality or 

clinical signs of toxicity were 

observed in any acute or subacute avian study and because 

usage of dikegulac-sodium is 

low, a study is not needed for 

risk assessment.

00073618 Acceptable 

850.2200 Avian dietary 

toxicity 

46547303 Acceptable Yes None

00059581 Supplemental 

00059582 Supplemental 

850.2300 Avian reproduction (None) (Not 

applicable) 

Yes None: no sublethal toxicity 

observed in acute studies, 

exposure potential is low due 

to the limited use pattern 
20 

OCSPP 

Guideline Data Requirement 

Submitted

Studies 

(MRID) 

Study 

Classifications 

Sufficient

for risk 

assessment? 

Current Additional Data 

Need

Nonguideline Avian inhalation (None) (Not 

applicable) 

Yes None 

850.3020 Honey bee acute 

contact toxicity 

44093910 Acceptable Yes None 

Nonguideline Honey bee acute 

oral toxicity 

(None) (Not 

applicable) 

No An acute oral toxicity study 

with the adult honey bee is 

needed. 

Nonguideline Honey bee larval 

chronic toxicity 

(None) (Not 

applicable) 

No A repeat dose larval toxicity 

study with the honey bee is 

needed. 

Nonguideline Honey bee adult 

chronic 10d toxicity 

(None) (Not 

applicable) 

No A chronic 10 day oral toxicity 

study with the adult honey bee 

is needed. 

850.3030 Honey bee residue 

on foliage 

(None) (Not 

applicable) 

Yes None

850.3040 Field testing for 

pollinators 

(None) (Not 

applicable) 

Yes None

850.4100 Seedling Emergence 46547305 Acceptable Yes None 

850.4150 Vegetative Vigor 46547306 Acceptable Yes None 

Study Title: Honey Bee Acute Oral Toxicity Test 

Guideline Number: Non-guideline 

Test Substance: Dikegulac-sodium—TGAI 

Rationale for Requiring the Data

This study is needed to evaluate potential effects to adult honey bees from acute oral exposure 

to technical grade active ingredient (TGAI). Dikegulac-sodium uses include applications to 

flowering ornamental plants via ground spray. Target plants may be visited by pollinators, and 

spray drift may land on blooming non-target plants and result in residues in pollen and nectar 

(which could then be transported to the hive). Dikegulac-sodium is systemic and may move 

into pollen and/or nectar in a plant. Residues can in turn be brought back to bee colonies where 

in-hive bees including young adult and developing brood (i.e., eggs, larvae and pupae) may be 

exposed. Therefore, exposure at all bee life stages would be expected. 

The Agency guidance for assessing the risk of pesticides to bees (USEPA et al., 2014) requires 

this study for all use sites where potential exposure to pollinators may occur. Although EPA 

has not developed a guideline for this study, the Organization for Economic Cooperation and 

Development (OECD) has developed a formal test guideline for an acute oral toxicity study 

with adult honey bees (OECD TG213) that may be used to assess the acute oral toxicity for 

adult bees. 
21 

Practical Utility of the Data 

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

The acute oral toxicity data are used in conjunction with acute contact data obtained through 

OCSPP 850.3020 to estimate the acute toxicity of technical grade active ingredient (TGAI) to 

individual young adult honey bees. The studies also provide slopes for the dose-response 

curves that can in turn be used for estimating the likelihood of individual effects, and sublethal 

effects observed in the study will be used to further characterize effects observed following a 

single exposure to TGAI. Data obtained from this study will be used in estimating acute risk to 

individual adult bees. Risk estimates based on these data will be considered along with other 

lines of evidence to determine whether higher-tier studies are needed at the whole colony 

level. 

These data are needed for risk assessments written in support of Registration Review risk 

assessment as well as for future endangered species assessments. The data would allow the 

Agency to better characterize the potential for risk to insects (including beneficial pollinators) 

from the use of dikegulac-sodium. These data may help the Agency determine whether any 

mitigations are needed. If the Registration Review and any future endangered species risk 

assessments are performed without these data, the Agency would have to assume that 

dikegulac-sodium "may affect" insects, including bees and beneficial pollinators, directly (and 

endangered species from other taxa indirectly), and uses of dikegulac-sodium might need to be 

restricted in areas where pollinators could be exposed. 

Study Title: Larval Honey Bee Acute and Chronic Oral Toxicity 

Guideline Number: Non-guideline 

Test Substance: Dikegulac-sodium—TGAI 

Rationale for Requiring the Data 

These studies are needed to evaluate the potential effects of technical grade active ingredient 

(TGAI) on honey bee larvae from repeat exposure. Dikegulac-sodium uses include 

applications to flowering ornamental plants via ground spray. Target plants may be visited by 

pollinators, and spray drift may land on blooming non-target plants and result in residues in 

pollen and nectar (which could then be transported to the hive). Dikegulac-sodium is systemic 

and may move into pollen and/or nectar in a plant. Residues can in turn be brought back to bee 

colonies where in-hive bees including young adult and developing brood (i.e., eggs, larvae and 

pupae) may be exposed. Therefore, exposure at all bee life stages may occur. 

The Agency guidance for assessing the risk of pesticides to bees (USEPA et al., 2014) requires 

this study for all use sites where potential exposure to pollinators may occur. Although EPA 

has not developed a guideline for this study, the 21-day larval toxicity study currently under 

development by OECD provides a draft guidance protocol for potentially assessing both the 

acute and chronic toxicity to developing brood (larvae and pupae) from repeat exposure to 

pesticides. Until a guideline is finalized, protocols should be submitted to the Agency for 

review before study initiation. Registrants may choose to submit a separate acute (single dose) 

larval toxicity study following OECD TG 237 as well as the 21-day repeat dose chronic 

toxicity study. 
22 

Practical Utility of the Data 

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

The 21-day toxicity study provides data on the effects of technical grade active ingredient 

(TGAI) on developing bees from acute (short-term) and chronic (longer term) exposure and 

will be used for estimating risk to individual (solitary) bees as well as bee colonies (social 

bees). Risk estimates based on these data will be considered along with other lines of evidence 

to determine whether higher-tier studies are needed at the whole colony level. 

These data are needed for risk assessments written in support of Registration Review as well 

as for future endangered species assessments. These data would allow the Agency to better 

characterize the potential for risk to insects (including beneficial pollinators) from the use of 

dikegulac-sodium. These data may help the Agency determine whether any mitigations are 

needed. If the Registration Review and any future endangered species risk assessments are 

performed without these data, the Agency would have to assume that dikegulac-sodium "may 

affect" insects, including bees and beneficial pollinators, directly (and endangered species 

from other taxa indirectly), and uses of dikegulac-sodium might need to be restricted in areas 

where pollinators could be exposed. 

Study Title: Adult Honey Bee Chronic Oral Toxicity 

Guideline Number: Non-guideline 

Test Substance: Dikegulac-sodium—TGAI 

Rationale for Requiring the Data 

This study is needed to evaluate the potential effects of technical grade active ingredient 

(TGAI) on young adult honey bees from repeat exposure. Dikegulac-sodium uses include 

applications to flowering ornamental plants via ground spray. Target plants may be visited by 

pollinators, and spray drift may land on blooming non-target plants and result in residues in 

pollen and nectar (which could then be transported to the hive). Dikegulac-sodium is systemic 

and may move into pollen and/or nectar in a plant. Residues can in turn be brought back to bee 

colonies where in-hive bees including young adult and developing brood (i.e., eggs, larvae and 

pupae) may be exposed. Therefore, exposure at all bee life stages may occur. 

The Agency guidance for assessing the risk of pesticides to bees (USEPA et al., 2014) requires 

this study for all use sites where potential exposure to pollinators may occur. Although EPA 

has not developed a guideline for this study and OECD has yet to finalize test guidance for 

chronic studies, efforts are currently underway to develop standardized guidelines for 

assessing effects from chronic (10-day) exposures to adult bees in the laboratory. Until a 

guideline is finalized, a protocol should be submitted to the Agency for review before study 

initiation.

Practical Utility of the Data 

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

The 10-day toxicity study with young adult bees provides data that will be used in estimating 

chronic risk to individual adult bees. Risk estimates based on these data will be considered along 
23 

with other lines of evidence to determine whether higher-tier studies are needed at the whole 

colony level. 

These data are needed for risk assessments written in support of Registration Review as well 

as for future endangered species assessments. These data would allow the Agency to better 

characterize the potential for risk to insects (including beneficial pollinators) from the use of 

dikegulac-sodium. These data may help the Agency determine whether any mitigation is 

needed. If the Registration Review and any future endangered species risk assessments are 

performed without these data, the Agency would have to assume that dikegulac-sodium "may 

affect" insects, including bees and beneficial pollinators, directly (and endangered species 

from other taxa indirectly), and uses of dikegulac-sodium might need to be restricted in areas 

where pollinators could be exposed. 

10. References 

Budavari, S., M. O’Neil, A. Smith, P. Heckelman, and J. Obenchain. 1996. The Merck 

Index, 12th edition. Merck & Co., Inc., Whitehouse Station, NJ. 

Meylan, W.M. and P.H. Howard. 1995. Atom/fragment contribution method for estimating 

octanol–water partition coefficients. J. Pharm. Sci., 84: 83–92. 

doi: 10.1002/jps.2600840120 

Neely, W.B. and G.E. Blau. 1985. Environmental Exposure from Chemicals, Vols. I and II. CRC 

Press Inc., Boca Raton, FL. 

United States Environmental Protection Agency (USEPA). 2004. Overview of the Ecological 

Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental 

Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects 

Division. Available at http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

USEPA. 2006a. Barnes, Y., J. Facey, R. Griffen, and S. Recore. Dikegulac Sodium: Human 

Health Considerations for the Reregistration Eligibility Decision. DP barcode 317256. 

U.S. Environmental Protection Agency, Office of Prevention, Pesticides, and Toxic 

Substances, Health Effects Division. Memorandum to the Special Review and 

Reregistration Division. Oct. 31, 2006. 

USEPA. 2006b. Eckel, W., M. Davey, and J. Martinez. EFED Risk Assessment for the 

Reregistration of Dikegulac-Sodium. DP barcode 317851. U.S. Environmental Protection 

Agency, Office of Prevention, Pesticides, and Toxic Substances, Environmental Fate and 

Effects Division. Memorandum to the Special Review and Reregistration Division. Oct. 

6, 2006. 

USEPA. 2007a. Eckel, W. Drinking Water Assessment for Dikegulac-sodium Reregistration 

Eligibility Decision (RED). DP barcode 322063. U.S. Environmental Protection Agency, 

Office of Prevention, Pesticides, and Toxic Substances, Environmental Fate and Effects 

Division. Memorandum to the Special Review and Reregistration Division. Feb. 9, 2007. 
24 

USEPA. 2007b. 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/ 

USEPA, PMRA, and CDPR, 2014. Guidance for Assessing Pesticide Risks to Bees. Office of 

Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management 

Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, 

Sacramento, CA. June 23, 2014. 

a. Submitted Environmental Fate Studies 

MRID Citation Reference 

46932401 Wisocky, M. (2006) Hydrolysis of [14-Carbon] Dikegulac in Buffered Water at pH 5, 6, 7 and 9. 

Project Number: XBL/03002, RPT01447. Unpublished study prepared by Xenobiotic, Inc. 261 p. 

46932402 Wisocky, M. (2006) Aerobic Soil Metabolism of [14-Carbon] Dikegulac. Project Number: 

XBL/03001, RPT01572. Unpublished study prepared by Xenobiotic, Inc. 309 p. 

46939501 Wisocky, M. (2006) Adsorption and Desorption of (Carbon 14) Dikegulac in Four US Soils. Project 

Number: XBL/03003, RPT01612. Unpublished study prepared by Xenobiotic, Inc. 239 p. 

b. Submitted Ecological Toxicity Studies 

MRID Citation Reference 

00059581 Ross, D.B.; Burroughs, S.J.E.; Roberts, N.L. (1974) The Acute Toxicity (LCI50^) of RO/7-6145 to 

the Japanese Quail: HLR/13/74911. (Unpublished study received Aug 1, 1975 under 35977-EX-1; 

pre- pared by Huntingdon Research Centre, England, submitted by Hoffman-Laroche, Inc., Nutley, 

N.J.; CDL:223552-BW) 

00059582 Ross, D.B.; Burroughs, S.J.; Roberts, N.L. (1975) The Sub-acute Toxicity (LCI50^) of RO 7-6145 to 

the Chicken: HLR26/75343. (Unpublished study received Aug 1, 1975 under 35977-EX-1; prepared 

by Huntingdon Research Centre, England, submitted by Hoffman-Laroche, Inc., Nutley, N.J.; 

CDL:223552-BX) 

00059583 Moore, G.E. (1974) The Acute Toxicity of RO07-6145 to the Bluegill Sunfish,~Lepomis 

macrochirus~: Report No. 746-122. (Unpub- lished study received Aug 1, 1975 under 35977-EX-1; 

prepared by Huntingdon Research Centre, England, submitted by Hoffman- Laroche, Inc., Nutley, 

N.J.; CDL:223552-BY) 

00059584 Fraser, W.D.; Jenkins, G. (1974) The Acute Toxicity of RO-07-6145 (Technical) to Rainbow Trout 

(~Salmo gairdneri~): HLR/8/74758. (Unpublished study received Aug 1, 1975 under 35977-EX-1; 

pre- pared by Huntingdon Research Centre, England, submitted by Hoffman-Laroche, Inc., Nutley, 

N.J.; CDL:223552-BZ) 

00059585 Fraser, W.D.; Jenkins, G. (1974) The Acute Toxicity of RO-07-6145 (Technical) to Harlequin Fish 

(~Rasbora heteromorpha~): HLR/ 12/74773. (Unpublished study received Aug 1, 1975 under 35977- 

EX-1; prepared by Huntingdon Research Centre, England, submitted by Hoffman-Laroche, Inc., 

Nutley, N.J.; CDL:223552-CA) 

00059586 Fraser, W.D.; Jenkins, G. (1974) The Acute Toxicity of RO-07-6145 (Technical) to Goldfish 

(~Carassius auratus~): HLR/11/74759. (Unpublished study received Aug 1, 1975 under 35977-EX-1; 

pre- pared by Huntingdon Research Centre, England, submitted by Hoffman-Laroche, Inc., Nutley, 

N.J.; CDL:223552-CB) 
25 

MRID Citation Reference 

00065378 Ross, D.B.; Cameron, D.M.; Roberts, N.L. (1976) The Effect of Contact with ACR 1139A and ACR 

4031 on the Hatchability of Fertile Quail Eggs: HLR/38/76480. (Unpublished study received on 

unknown date under 35977-EX-1; prepared by Huntingdon Research Centre, England, submitted by 

Hoffman-Laroche, Inc., Nutley, N.J.; CDL:229051-E) 

00073618 Ross, D.B.; Burroughs, S.J.E.; Roberts, N.L. (1974) The Acute Toxicity of RO/7-6145 to the Mallard 

Duck: HLR14/74653. (Unpublished study received Aug 1, 1975 under 35977-EX-1; prepared by 

Huntingdon Research Centre, England, submitted by Hoffman- Laroche, Inc., Nutley, N.J.; 

CDL:223552-BV) 

00073618 Ross, D.B.; Burroughs, S.J.E.; Roberts, N.L. (1974) The Acute Toxicity of RO/7-6145 to the Mallard 

Duck: HLR14/74653. (Unpublished study received Aug 1, 1975 under 35977-EX-1; prepared by 

Huntingdon Research Centre, England, submitted by Hoffman- Laroche, Inc., Nutley, N.J.; 

CDL:223552-BV) 

43064617 Backes, G. (1977) Embryotoxicity Studies in the Rat Following Oral Administration of Ro 07-

6145/001. Unpublished study prepared by Roche Corporate Lab. 177 p. 

43064618 Backes, G. (1977) Embryotoxicity Studies in the Rabbit Following Oral Administration of Ro 07-

6145/001. Unpublished study prepared by Roche Corporate Lab. 96 p. 

44093901 Douds, D. (1995) An Acute Oral Toxicity Study (Limit Test) in Rats with Dikegulac Sodium: Final 

Report: Lab Project Number: 3229.102: EPA/AO-1-2/94. Unpublished study prepared by Springborn 

Labs, Inc. 37 p. 

44093903 Douds, D. (1995) An Acute Whole-Body Inhalation Toxicity Study (Limit Test) in Rats with 

Dikegulac Sodium: Final Report: Lab Project Number: 3229.104: EPA/AI-1-2/94. Unpublished study 

prepared by Springborn Labs, Inc. 59 p. 

44093910 Palmer, S.; Beavers, J. (1996) Dikegulac Sodium: An Acute Contact Toxicity Study with the Honey 

Bee: Final Report: Lab Project Number: 281-113: 281/030895/BLD.NC/CHP86. Unpublished study 

prepared by Wildlife International Ltd. 29 p. 

45631702a Fraser, W.D. and Jenkins, G. (1975) The Acute Toxicity ofRO-07-6145 to the black carp (Cyprinus 

carpio). Unpublished study performed by Huntington Research Center, Cambridgeshire, England. 

Laboratory Study No. Not reported. Sponsor not reported. 

45631702b Fraser, W.D. and Pell, L.B. (1977) The Acute Toxicity of RO-76145.001 to the Brown Shrimp 

(Crangon crangon). Unpublished study performed by Huntington Research Center, Cambridgeshire, 

England. Laboratory Study No. Not reported. Study sponsored by Hoffman La Rouche Ltd. 

45631702c Leblanc, G.A. 1977. Acute Toxicity of RO 7-6145/001to the water flea (Daphnia magna). 

Unpublished study performed by EG & G, Bionomics, Aquatic Toxicology Laboratory, Wareham, 

Massachusetts. Laboratory Study No. Not reported. Study sponsored by Hoffman-LaRoche, Inc., 

Nutley, New Jersey. 

46547301 Palmer, S.; Kendall, T.; Krueger, H. (2004) Dikegulac: A 96-Hour Static-Renewal Acute Toxicity 

Test with the Rainbow Trout (Oncorhynchus mykiss): Final Report. Project Number: 281A/127A. 

Unpublished study prepared by Wildlife International, Ltd. 56 p. 

46547302 Gallagher, S.; Beavers, J. (2004) Dikegulac: An Acute Oral Toxicity Study with the Northern 

Bobwhite. Project Number: 281/114. Unpublished study prepared by Wildlife International, Ltd. 38 

p. 

46547303 Gallagher, S.; Martin, K.; Beavers, J. (2004) Dikegulac: A Dietary LC50 Study with the Northern 

Bobwhite. Project Number: 281/115. Unpublished study prepared by Wildlife International, Ltd. 47 

p. 
26 

MRID Citation Reference 

46547305 Brignole, A.; Porch, J.; Krueger, H.; et. al. (2004) Dikegulac: A Toxicity Test to Determine the 

Effects of the Test Substance on Seedling Emergence of Ten Species of Plants: Final Report. Project 

Number: 281/116. Unpublished study prepared by Wildlife International, Ltd. 99 p. 

46547306 Brignole, A.; Porch, J.; Krueger, H.; et. al. (2004) Dikegulac: A Toxicity Test to Determine the 

Effects of the Test Substance on Vegetative Vigor of Ten Species of Plants: Final Report. Project 

Number: 281/117. Unpublished study prepared by Wildlife International, Ltd. 167 p. 

46547307 Desjardins, D.; Kendall, T.; Krueger, H. (2004) Dikegulac: A 7-Day Toxicity Test with Duckweed 

(lemna gibba G3): Final Report. Project Number: 281A/132. Unpublished study prepared by Wildlife 

International, Ltd. 59 p. 

46547308 Desjardins, D.; Kendall, T.; Krueger, H. (2005) Dikegulac: A 96-Hour Toxicity Test with the 

Freshwater Alga (Selenastrum capricornutum): Final Report. Project Number: 281A/128. 

Unpublished study prepared by Wildlife International, Ltd. 67 p. 

46547309 Desjardins, D.; Kendall, T.; Krueger, H. (2004) Dikegulac: A 96-Hour Toxicity Test with the 

Freshwater Alga (Anabaena flos-aquae): Final Report. Project Number: 281A/129. Unpublished 

study prepared by Wildlife International, Ltd. 56 p. 

46547310 Desjardins, D.; Kendall, T.; Krueger, H. (2005) Dikegulac: A 96-Hour Toxicity Test with the 

Freshwater Diatom (navicula pelliculosa): Final Report. Project Number: 281A/131. Unpublished 

study prepared by Wildlife International, Ltd. 56 p. 

46547311 Desjardins, D.; Kendall, T.; Krueger, H. (2004) Dikegulac: A 96-Hour Toxicity Test with the Marine 

Diatom (Skeletonema costatum): Final Report. Project Number: 281A/130. Unpublished study 

prepared by Wildlife International, Ltd. 54 p. 
27 

Appendix A. Dikegulac-sodium Ecotoxicity Data 

Toxicity to Terrestrial Animals

Avian Toxicity

Table A-1. Acute Oral Toxicity of Dikegulac-sodium to Birds

Species % ai LD50

(mg ae/kg-bw) Toxicity Category MRIDAuthor, Year 

Study 

Classification 

Northern bobwhite quail 

(Colinus virginianus)

96.9 >2083 1 Practically non-toxic 46547302 

Gallagher, et. al., 2004 

Acceptable

Mallard duck 

(Anas platyrhynchos)

20 >3891 1 Practically non-toxic 00073618 

Ross, et. al., 1974 

Acceptable

1 No mortality of toxicity occurred at the highest concentration tested. 

Table A-2. Subacute Dietary Toxicity of Dikegulac-sodium to Birds

Species % ai LC50

(ppm ae) Toxicity Category MRIDAuthor, Year 

Study

Classification 

Northern bobwhite quail 98.9 >5460 1 Practically non-toxic 46547303 

Gallagher, et. al., 2004 

Acceptable 

Mallard duck 20 >50,000 Practically non-toxic 00073618 

Ross, et. al., 1974 

Acceptable 

Japanese quail 

(Coturnix japonica)

20 >50,000 1 Practically non-toxic 00059581 

Ross, et. al., 1974 

Supplemental 2

Chicken 

(Gallus gallus domesticus) 

20 >50,000 1 Practically non-toxic 00059582 

Ross, et. al., 1974 

Supplemental 2

1

 No mortality at highest concentration tested. 

2

 Supplemental due to non-standard species and lack of raw data. 

Avian Chronic Toxicity

No reproduction studies are available for avian species. 

Mammalian Toxicity 

Table A-3. Mammalian Toxicity of Dikegulac-sodium

Species % ai Test Type Toxicity Value 

(mg ai/kg-bw) 

Most Sensitive 

Endpoints MRID

Laboratory rat 

(Rattus norvegicus) 

100 Acute Oral LD50 >5000 1 No mortality or other signs of 

toxicity were noted at the 

highest concentration tested. 

44093901 

Rabbit2

(Oryctolagus cuniculus) 

93 - 97 Developmental Toxicity NOAEL = 700 

LOAEL = 2000 

Maternal lack of weight gain 

(92% decrease compared to 

controls), diarrhea 

43064618 

Laboratory rat (abino) 93 - 97 Developmental Toxicity NOAEL = 700 

LOAEL = 2000 

Light sedation 43064617 

1

 Male and female. Equivalent to >4612 mg ae/kg-bw. 

2

 No fetal parameters including litter size, litter weight or viability were affected. Nominal concentrations tested: 0, 200, 700, 2000 mg a.i./kg/day 

(0, 184, 646, 1845 mg ae/kg/day). No measured concentrations provided. 

No mammalian reproductive study was available so results from development toxicity studies are 

reported. The rat developmental study was not considered to be significant for ecological based 

risk. 
28 

Terrestrial Invertebrate Toxicity 

Table A-4. Nontarget Insect Acute Contact Toxicity of Dikegulac-sodium

Species % ai LD50

(μg/bee) Toxicity Category MRID No. Author, Year 

Study

Classification 

Honey bee (Apis mellifera) 15.0 LD50 >81 Practically non-toxic 

44093910 

Palmer et. al., 1996 Acceptable 

Toxicity to Aquatic Animals

Aquatic Vertebrate Toxicity 

Table A-5. Freshwater Fish Acute Toxicity of Dikegulac-sodium 

Species % ai 

96-hour

LC50 (ppm ae) Toxicity Category MRID No. Author, Year 

Study

Classification

Rainbow trout, 

(Oncorhychus mykiss) 

86.4 >121 1 Practically non-toxic 46547301 

Kendall et. al., 2004 

Acceptable 

Rainbow trout, 90.0 >10,000 1 Practically non-toxic 00059584 

Fraser, et. al., 1974 

Acceptable 

Bluegill sunfish, 

(Lepomis macrochirus) 

90.0 >10,000 1 Practically non-toxic 00059583 

Moore, 1974 

Acceptable

Goldfish 

(Carassius auratus) 

90.0 > 5,000 1 Practically non-toxic 00059586 

Fraser, et. al., 1974 

Supplemental 2

1 No mortality or other signs of toxicity at the highest treatment level were noted. 

2 Gold fish is not a preferred species 

Freshwater Fish Chronic Toxicity 

No fish early-life stage or fish life cycle studies are available for dikegulac-sodium. 

Aquatic Invertebrate Toxicity 

Table A-6. Acute Toxicity of Dikegulac-sodium to Freshwater Invertebrates

Species % ai 

48-hour LC50

(ppm ae) Toxicity Category 

MRID No. 

Author, Year 

Study

Classification 

Waterflea 

(Daphnia magna) 

Tech. > 10,000 1 Practically non-toxic 45631702 

Mileson, 2002 

Supplemental

1

 There was no mortality at the highest treatment concentration (10,000 ppm) but signs of stress were exhibited at that concentration in which the 

organisms remained on the surface during the test. The NOEC is 3200 ppm and LOEL is 10,000 ppm. The study is supplemental due to lack of 

raw data. This study was conducted by LeBlanc, 1977 but is found within MRID 45631702. 

Table A-7. Acute Toxicity of Dikegulac-sodium to Estuarine/Marine Invertebrates

Species % ai 48-hour LC50

(ppm ae) Toxicity Category MRID No. Author, Year 

Study

Classification 

Brown shrimp 1

(Crangon crangon) (static) 

Tech. 8,783 Practically non-toxic 45631702 

Mileson, 2002 

Supplemental 

1

 100% mortality was observed at the 20,000 ppm concentration dose. The study is supplemental due to lack of raw data. This study was 

conducted by Fraser, 1977 but is found within MRID 45631702. 

Aquatic Invertebrate Chronic Toxicity 

No chronic aquatic invertebrate studies are available for dikegulac-sodium. 
29 

Toxicity to Plants

Terrestrial Plant Toxicity

 

Table A-8. Summary of Effects of Dikegulac-sodium (Atrimmec, 18.5% a.i.) on Vegetative Vigor (Tier II) 

Species 

NOAEC, and EC25 (lbs ae/A) 

Plant Height Dry Weight Survival

NOAEC EC25 NOAEC EC25 NOAEC EC25

Corn (Zea mays) 0.5 2.8 0.5 2.0 1.5 >1.5 

Onion (Allium cepa) 1.6 >4.9 1.6 >4.9 1.6 >4.9 

Perennial Ryegrass (Lolium 

perenne)

1.3 >4.5 0.5 1.7 1.3 >4.5 

Wheat (Triticum aestivum) 1.3 3.3 1.3 1.9 1.3 >1.3 

Bean (Phaseolus vulgaris) 1 0.2 0.61 0.5 1.3 4.3 >4.3 

Cabbage (Brassica oleracea) 1.6 3.7 1.6 2.1 4.9 >4.9 

Lettuce (Lactuca sativa) 1.5 2.2 0.5 1.0 1.5 >1.5 

Radish (Raphanus sativus) 1.6 >4.9 1.6 2.1 4.9 >4.9 

Soybean (Glycine max) 1.5 3.0 0.5 2.3 4.3 >4.3 

Tomato (Solanum lycopersicum) 0.5 1.3 0.2 0.72 4.9 >4.9 

MRID 46547306: Brignole, Andrew, J. R. Porch, H. O. Krueger and K. H. Martin. 2004. 

1

 Bean is the most sensitive species tested. Bold text denotes the most sensitive value. 

Table A-9. Summary of Effects of Dikegulac-sodium (Atrimmec, 18.5% a.i.) on Seedling Emergence

Species 

NOAEC, and EC25 (lbs ae/A) 

Seedling Height Seedling Weight Emergence 

NOAEC EC25 NOAEC EC25 NOAEC EC25

Tier II 

Corn 4.6 >4.6 4.6 >4.6 4.6 >4.6 

Onion 1 4.6 >4.6 4.6 ND <0.29 1 0.50 

Cabbage 2.3 4.7 2.3 4.7 4.5 >4.5 

Radish 2 1.2 3.2 2.3 3.4 1.2 20 

Tomato 2.3 4.8 2.3 4.1 4.5 >4.5 

Tier I 

Perennial Ryegrass 4.6 >4.6 4.6 >4.6 4.6 >4.6 

Wheat 4.6 >4.6 4.6 >4.6 4.6 >4.6 

Bean 4.6 >4.6 <4.6 >4.6 4.6 >4.6 

Lettuce <4.6 >4.6 <4.6 >4.6 <4.6 >4.6 

Soybean 4.6 >4.6 4.6 >4.6 4.6 >4.6 

MRID 46547305: Brignole, Andrew, J. R. Porch, H. O. Krueger and K. H. Martin. 2004. 

ND: Not Determined 

1

 Onion EC05 or NOAEC cannot be determined due to the non-linear distribution of the data; the onion values may not be reliable. 2

 Radish is the most sensitive species tested. Bold text denotes the most sensitive value. 
30 

Aquatic Plant Toxicity

Table A-10. Toxicity of Dikegulac-sodium to Aquatic Plants (Tier II)

Species % ai EC50

(ppm ae) 

EC05 or NOAEC 

(ppm ae) 

MRID No. 

Author (Year) Study Classification 

Duckweed (Lemna gibba) 96.9 9.6 1 3.5 46547307 

Desjardins et. al., 2004 

Supplemental 3

Green algae (Selenastrum 

capricornutum) 

96.9 100 2 27 46547308 

Desjardins et. al., 2004 

Acceptable 

Blue-green cyanobacteria 

(Anabaena flos-aquae)

96.9 >120 2 15 46547309 

Desjardins et. al., 2004 

Acceptable 

Freshwater diatom 

(Navicula pelliculosa) 

96.9 >112 2 112 46547310 

Desjardins et. al., 2004 

Acceptable 

Marine diatom 

(Skeletonema costatum) 

96.9 >106 2 26 46547311 

Desjardins et. al., 2004 

Supplemental 4

1

 Based on frond numbers. 

2

 Based on cell density. 

3

 The duckweed test is a static test instead of renewal test. 

4

 Cell density (77,000 cells/ml) is higher than recommended (10,000 cells/ml).