UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

PC Code: 112600

DP Barcode: 403899

November 20, 2012

MEMORANDUM

Subject: Registration Review: Problem Formulation for the Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments 

for Prohexadione Calcium

To: Katie Weyrauch, Chemical Review Manager

Margarita Collantes, Acting Team Leader

Pesticide Re-evaluation Division (7508P)

Office of Pesticide Programs

From: Anita Ullagaddi, Biologist

Stephen Wente, Biologist

Ed Odenkirchen, Acting Branch Chief

Environmental Risk Branch 1

Environmental Fate and Effects Division (7507P)

Office of Pesticide Programs

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

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

exposure assessments to be conducted as part of the Registration Review of the plant growth 

regulator prohexadione calcium. 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 prohexadione calcium and its 

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

evaluating and characterizing drinking water exposure and risk to non-target species and the 

environment in support of the Registration Review of prohexadione calcium. This document also 

recommends studies that should be included in a data call-in (DCI) to address uncertainties 

surrounding the environmental fate and potential ecological effects of prohexadione calcium.
1

Problem Formulation for the Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking 

Water Exposure Assessments in Support of the 

Registration Review of Prohexadione Calcium

calcium 3-oxido-5-oxo-4-propionylcyclohex-3-enecarboxylate

CAS Registry Number: 127277-53-6

PC Code: 112600

Prepared by:

Anita Ullagaddi, M.S., Biologist

Stephen Wente, Ph.D., Biologist

U. S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

1200 Pennsylvania Avenue, NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Robin Sternberg, Ph.D., Wildlife Biologist

He Zhong, Ph.D., Biologist

November 20, 2012

C

O

OO

-O

C

O

H2C

H3C

Ca2+
2

Table of Contents

1. Purpose....................................................................................................................................... 3

2. Problem Formulation ................................................................................................................. 3

2.1. Nature of Regulatory Action............................................................................................... 3

2.2. Previous Assessments......................................................................................................... 3

2.2.1. Ecological Risk and Drinking Water Assessments...................................................... 3

3. Stressor Source and Distribution ............................................................................................... 4

3.1. Mode of Action................................................................................................................... 4

3.2. Overview of Pesticide Use and Usage ................................................................................ 4

3.3. Environmental Fate and Transport...................................................................................... 5

3.4. Clean Water Act.................................................................................................................. 8

4. Receptors.................................................................................................................................... 8

4.1. Effects to Aquatic Organisms............................................................................................. 8

4.2. Effects to Terrestrial Organisms......................................................................................... 9

4.3. Incident Databases Review............................................................................................... 11

4.4. Ecosystems Potentially at Risk ......................................................................................... 11

5. Assessment Endpoints ............................................................................................................. 11

6. Conceptual Model.................................................................................................................... 11

6.1. Risk Hypothesis................................................................................................................. 12

6.2. Conceptual Diagram ......................................................................................................... 12

7. Analysis Plan ........................................................................................................................... 15

7.1. Stressors of Concern ......................................................................................................... 15

7.2. Measures of Exposure....................................................................................................... 16

7.3. Measures of Effect ............................................................................................................ 17

7.4. Integration of Exposure and Effects ................................................................................. 17

7.5. Deterministic and Probabilistic Assessment Methods...................................................... 17

7.6. Endangered Species Assessment ...................................................................................... 18

7.7. Endocrine Disruptor Screening Program.......................................................................... 18

7.8. Human Health Drinking Water Assessment..................................................................... 19

7.9. Preliminary Identification of Data Gaps........................................................................... 19

7.9.1. Fate Data Gaps........................................................................................................... 19

7.9.2. Effects Data Gaps ...................................................................................................... 23

8. References................................................................................................................................ 27

Appendix A. Chemical Structures of Prohexadione Calcium and Its Degradates.................... 28

Appendix B. Prohexadione Calcium Incidents......................................................................... 30
3

1. Purpose

This document will provide a plan for analyzing data relevant to prohexadione calcium and for 

conducting ecological risk, endangered species, and drinking water exposure 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 prohexadione calcium.

2. Problem Formulation

2.1. Nature of Regulatory Action

In 1996, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended by the 

Food Quality Protection Act (FQPA), and the United States Environmental Protection Agency

(the Agency or EPA) was mandated to implement a new program for the periodic review of 

pesticides, i.e., Registration Review (http://www.epa.gov/oppsrrd1/registration_review/). 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 prohexadione calcium to determine whether it 

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

ecological risk, endangered species, and drinking water assessment chapter in support of the 

Registration Review will be posted in the initial docket, which will open the public phase of the 

review process.

2.2. Previous Assessments

2.2.1. Ecological Risk and Drinking Water Assessments

Prohexadione calcium was first registered in 2000. The ecological risk and drinking water 

assessments conducted by EFED are summarized in Table 2.1. The risk assessments identified 

potential chronic risks to freshwater and estuarine/marine fish, mammals, as well as risks to 

terrestrial and semi-aquatic plants.

Table 2.1. Summary of Previous Ecological Risk and Drinking Water Assessments

Date Title DP Barcode

Drinking Water Assessments

1/24/2000 Tier I prohexadione calcium Estimated Environmental Concentrations in Drinking 

Water for use on apples, peanuts, and grass grown for seed. D260214

2/23/2010 Prohexadione Calcium Drinking Water Assessment in Support of New Use 

Registration Action for Turf and Ornamentals D367843

4/1/2011 Tier II Drinking Water Exposure Assessment for Prohexadione Calcium in Support 

of the New Use Registration on Sweet Cherries D387297

Ecological Risk Assessments

4/18/2000 Section 3 For the Use Of Prohexadione Calcium (112600) on peanuts, apple and 

pear trees, and grass grown for seeds

D246696, 

D246700, 

D246727, 

D245631, 

D252545, 

D252597, and 

D264536
4

Table 2.1. Summary of Previous Ecological Risk and Drinking Water Assessments

Date Title DP Barcode

10/16/2000 Section 3 For the Use Of Prohexadione Calcium on grass grown for seed (Chem 

code 112600) 

D267906 and 

D267898

4/6/2010 Environmental Fate and Effects Division Risk Assessment for the Section 3 New

Use of Prohexadione Calcium D376230

4/11/2011 Ecological Risk Assessment to Support the Proposed Section 3 New Use of 

Prohexadione Calcium on Sweet Cherries D384104

3. Stressor Source and Distribution

Prohexadione calcium (calcium 3-oxido-5-oxo-4propionylcyclohex-3-enecarboxylate) is a plant 

growth regulator used in agricultural (apple, cherry, grasses grown for seed, ornamental sod farm 

(turf), peanuts, and pear) and nonagricultural settings (bermudagrass, commercial/industrial 

lawns, golf course turf, ornamental lawns and turf, recreation area lawns, and residential lawns). 

It is formulated as a dry flowable. Prohexadione calcium is applied by aerial and ground 

application to agricultural crops and by ground application for non-agricultural uses.

3.1. Mode of Action

Prohexadione calcium is a natural plant hormone that regulates plant cell elongation by 

inhibiting the biosynthesis of gibberellin. Inhibition of gibberellin results in reduction of shoot 

growth in plants. Prohexadione calcium’s mode of action in fire blight control is not currently

known.

3.2. Overview of Pesticide Use and Usage

The Biological and Economic Analysis Division (BEAD) provided a Screening Level Usage 

Analysis to provide estimates of the actual usage of prohexadione calcium on agricultural crops 

(USEPA, 2012a). Apples were the only crop reported, with estimated usage of 10,000 lb a.i. per 

year. The average crop area treated was 10%, with the maximum being 25%. BEAD also 

provided a use characterization in the form of a Label Data Report (USEPA, 2012b). Table 3.1

presents the agricultural and non-agricultural uses and corresponding application rates (single 

and maximum), application interval, and methods of application that will be considered in the 

Registration Review risk assessment. In the event that a parameter is not specified on the label, 

the Agency must make assumptions to estimate environmental exposure. Where possible, the 

registrant should provide information on all the parameters for all registered uses.

Prohexadione calcium agricultural uses include apple, cherry, grasses grown for seed, peanuts,

pear, and grasses grown for seed. Prohexadione calcium non-agricultural uses include 

bermudagrass, commercial/industrial lawns, golf course turf, ornamental lawns and turf, 

ornamental sod farm (turf), recreation area lawns, and residential lawns.
5

Table 3.1. Maximum Labeled Application Rates for Prohexadione Calcium Uses

Use Site Application 

Method

Maximum Single 

Application Rate

(lb a.i./acre)

Number of 

Applications

per Year

Maximum 

Seasonal 

Application Rate

(lb a.i./acre)

Application 

Interval

(days)

Agricultural Uses

Apple, pear

G 0.61875 NS (2.75) 1.70156 NS3

A

1

0.61875 NS (2.75) 1.70156 NS3

Cherry G 0.34375 NS (2) 0.68750 NS3

A

1

0.34375 NS (2) 0.68750 NS3

Peanuts G

2

0.12525 NS (3) 0.375 NS5

Grasses grown for 

seed

G

1

0.49844 NS (1) 0.49844 NS (NA)

A

1

0.49844 NS (1) 0.49844 NS (NA)

Non-agricultural Uses

Bermudagrass G 0.03008 NS4(17) NS (0.5113) 21

Commercial/industrial 

lawns, golf course 

turf, ornamental 

lawns and turf, 

ornamental sod farm 

(turf), recreational 

area lawns, residential 

lawns

G 0.74938 NS4(26) NS (19.484) 14

NS = Not specified; NA = Not applicable. Numbers in parentheses are assumed.

G = ground; A = aerial

The following footnotes are based on the Label Use Information System report of May 30th, 2012 (current 

as of 5/25/12):

1Not allowed in California

2Allowed in Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, North Carolina, New Mexico,

Oklahoma, South Carolina, Texas, Virginia

3Application intervals not specified on Apogee Plant Growth Regulator label (7969-188).

4Maximum number of applications per year not specified on GWN-6010 label (10163-315).

5Application intervals not specified on Apogee Plant Growth Regulator label (7969-188) and Baseline 

Plant Regulator label (10163-315).

3.3. Environmental Fate and Transport

The physicochemical properties of prohexadione calcium (Table 3.2) indicate that it is highly

soluble in water, not likely to bioaccumulate (KOW of 1.25 × 10-3), and not expected to volatilize 

from soil and water surfaces.

Table 3.2. Summary of Prohexadione Calcium Physical and Chemical Properties

Physical/Chemical Property Value (unit) Source

Chemical Structure C MRID 44457702

O

OO

-O

C

O

H2C

H3C

Ca2+
6

Table 3.2. Summary of Prohexadione Calcium Physical and Chemical Properties

Physical/Chemical Property Value (unit) Source

CAS Chemical Name Cyclohexanecarboxylic acid, 3,5-dioxo-4-(1-

oxopropyl)-, ion (1-), calcium, calcium salt MRID 44457702

CAS No. 127277-53-6 MRID 44457702

Molecular Formula C10H10O2Ca MRID 44457702

Molecular Weight 250.27 g/mole MRID 44457702

SMILES Code

[Ca+2].O=C1C(=C(\[O-

])CC)/C(=O)CC(C(=O)O)C1.[O-

]\C(=C1\C(=O)CC(C(=O)O)CC1=O)CC

PPDB1

Physical State Tan colored, extruded solid MRID 44457721

Density or Specific gravity (23.7

oC) 0.579 g/mL (free fall); 0.637 g/mL (packed) MRID 44457721

Dissociation constant (pKa) 5.15 (Ka = 7.14 × 10-6) MRID 44457713

Vapor Pressure (25oC) 1.737 × 10-5 Pa (1.303 × 10-7 mm Hg) MRID 44457712

Water Solubility (20oC) 174.2 mg/L @ 20oC MRID 44457709

Octanol-Water Coefficient( Log 

Kow )

-2.90 @20oC (KOW = 1.25 × 10-3) MRID 44457713

Henry’s Law Constant at 25oC 2.595 × 10-11 atm-m

3

/mol EPISUITE 4.1

1

http://sitem.herts.ac.uk/aeru/footprint/en/Reports/539.htm

Based on laboratory and field studies, prohexadione calcium is not expected to persist for an 

extended period of time in aerobic conditions. Prohexadione calcium's major route of 

degradation is soil microbial degradation in aerobic soils (T1⁄2 = 1.4 days). It degrades slowly 

under anaerobic conditions (T1⁄2 = 117 days in anaerobic aquatic metabolism study). It is subject 

to rapid hydrolysis under acidic conditions (T1⁄2 (pH 5) = 4.4 days) but is resistant to hydrolysis 

in higher pH environments (T1⁄2 (pH 7) = 65 days). Aqueous photolysis half-lives range from 10 

(pH 5) to 23 days (pH 9) (soil photolysis half-life is 32 days but was slower than the dark 

control). The parent dissipates with half-lives ranging from 0.8 to 20 days in various terrestrial 

field dissipation studies conducted on bare ground. Table 3.3 provides a more detailed summary 

of environmental fate characteristics of prohexadione calcium.

Table 3.3. Summary of Prohexadione calcium Environmental Fate Properties

Study Value

Major Degradates

Minor Degradates MRID # Study Status

Hydrolysis (T1⁄2)

4.4 days @ pH 5

65 days @ pH 7

Stable @ pH 9

Despropionyl – 92% (28 days @ pH 5) 44457782 Acceptable

Direct Aqueous 

Photolysis (T1⁄2)

23.2 days (pH 9)

9.9 days (pH 5)

Combination of citric acid and tricarballylic 

acid (peaks could not be separated) – 72.77% 

(362 hours @ pH5)

BX112-M-10 – 18.88% (283 hours @ pH 9)

Despropionyl – 4% (96 hours @ pH 5)

Unknown – 4.6% (96 hours @ pH 5)

CO2 – 8.43% (120 hours @ pH 5)

44457783 Acceptable
7

Table 3.3. Summary of Prohexadione calcium Environmental Fate Properties

Study Value

Major Degradates

Minor Degradates MRID # Study Status

Soil Photolysis

(T1⁄2)

32.4 days

Despropionyl – 15.21% (7 days)

Bound Residues – 10.28% (10 days)

CO2 – 20.41% (10 days)

Unknown – 9.03% (Day 15)

Volatiles – 0.16% (Day 10)

Values reported are from the irradiated 

samples only. Degradation was faster in the 

dark controls.

44457784 Unacceptable

Aerobic Soil 

Metabolism

(T1⁄2)

1.4 days in sandy 

loam soil at 25 °C

Bound Residues – 14.64% (5 days)

CO2 – 79.84% (30 days)

Despropionyl – 4.78% (5 days)

44457785 Acceptable

Anaerobic Soil 

Metabolism No study submitted

Anaerobic 

Aquatic 

Metabolism

(T1⁄2)

117 days at 25 °C

Despropionyl (water) – 53.26% (180 days)

Despropionyl (sediment) – 6.66% (365 days)

Bound Residues – 32.87% (365 days)

CO2 – 3.17% (137 days)

44457786 Supplemental

Aerobic 

Aquatic 

Metabolism

No study submitted

Soil 

Adsorption 

Coefficient 

(Kd)

1

0.50 (sand soil) 

9.1 (loamy sand)

2.8 (clay)

11 (loam)

Not Applicable 44457787 Acceptable

Terrestrial 

Field 

Dissipation 

(T1⁄2) (on bare 

soil)

1 day in loamy sand 

soil (NC)

0.8 days in sandy 

loam soil (TX)

Despropionyl was not stable in the freezer 

storage stability samples. Therefore, no 

degradate data was presented in either study.

444577912 Acceptable

15 days (NY)

20 days (CA)

5.7 days (OR)

447252133 Acceptable

Accumulation No study submitted

1 The Freundlich adsorption coefficient may not be an adequate representation of adsorption across all 

concentrations, and it cannot be assumed that Kfis equal to Kd. One of the l/N values (1.2) for adsorption was not 

within the range of 0.9 to 1.1. Others were 0.98 or 0.99. There was no linear relationship between the soil organic 

carbon content and the Kd for different soils (r2= 0.28). Linearized Kdf - determined via linearization method (van 

Genuchten et al, 1977) are reported herein.

2

In this study, prohexadione calcium (BAS 125 W; 75 DF) was broadcast applied three times as a spray (21-day

intervals) at rates of 0.15, 0.15, and 0.30 lb a.i./A to bare ground plots. These application rates are lower than 

registered application rates.

3 Half-lives (T1⁄2) obtained following two treatments of 2.0 lb a.i./acre with prohexadione calcium (BAS 125 W) 

broadcast at 14 day intervals.
8

3.4. Clean Water Act

Prohexadione calcium is not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act1. In addition, no Total Maximum Daily

Loads (TMDL) have been developed for the plant growth regulator2. The Impaired Waters and

Total Maximum Daily Loads website can be consulted for more information3. 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 Process4, in order to ensure they can be used quantitatively or 

qualitatively in pesticide risk assessments.

4. Receptors

Consistent with the process described in the Overview Document (USEPA, 2004), the risk 

assessment for prohexadione calcium will rely on a surrogate species approach. Acute and 

chronic toxicity data from studies submitted by pesticide registrants along with the available 

open literature will be used to evaluate the potential direct and indirect effects of prohexadione 

calcium to aquatic and terrestrial receptors. This includes 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) database5, 

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

terrestrial plants, and wildlife.

4.1. Effects to Aquatic Organisms

A summary of the aquatic toxicity data for prohexadione calcium from registrant-submitted 

studies is provided in Table 4.1. In general, prohexadione calcium is practically non-toxic to 

aquatic animals on an acute basis. Chronic effects to freshwater invertebrates were observed 

based on number of offspring produced per female; however, growth measurements were not 

made in the study. There were no chronic early-life stage studies for freshwater and 

estuarine/marine fish. In addition, there were no chronic studies for estuarine/marine 

invertebrates. Tier I studies were conducted for aquatic plants. 

 

1

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

2

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

3

http://www.epa.gov/owow/tmdl/

4

http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf

5

http://www.epa.gov/ecotox
9

Table 4.1. Summary of the Endpoints from Submitted Aquatic Toxicity Studies for 

Prohexadione Calcium

Study Type Species Toxicity Value & Category MRID & Status

Acute – Freshwater 

Fish

850.1075

Rainbow trout 

(Oncorhynchus mykiss)

96-hr LC50: >94.6 mg/L

Practically non-toxic

444577-30

Supplemental

(the limit concentration was 

94.6 mg/L rather than the 

required 100 mg/L)

Acute – Freshwater 

Fish

850.1075

Bluegill sunfish 

(Lepomis macrochirus)

96-hr LC50: >95.6 mg/L

Practically non-toxic

444577-29

Supplemental

(the limit concentration was 

95.6 mg/L rather than the 

required 100 mg/L)

Acute –

Estuarine/Marine 

Fish

850.1075

Sheepshead minnow

(Cyprinodon variegatus)

96-hr LC50: >122 mg/L

Practically non-toxic

444577-32

Acceptable

Acute – Freshwater 

Invertebrate

850.1010

Water flea 

(Daphnia magna)

48-hr EC50: >100 mg/L

Practically non-toxic

444577-31

Acceptable

Acute –

Estuarine/Marine 

Invertebrate

850.1025

Eastern oyster

(Crassostrea virginica)

96-hr EC50: >117 mg/L

Practically non-toxic

444577-33

Acceptable

Acute –

Estuarine/Marine 

Invertebrate

850.1035

Mysid shrimp 

(Americamysis bahia)

96-hr LC50: >125 mg/L

Practically non-toxic

444577-34

Supplemental

(age of mysids was not 

reported)

Chronic – Freshwater 

Invertebrate

850.1300

Water flea 

(Daphnia magna)

NOAEC: 12.5 mg/L

LOAEC: 25 mg/L

(based on number of offspring per 

female)

444577-35

Supplemental

(growth of organisms was not 

measured)

Aquatic – Nonvascular Plants

850.4500 & 

850.4550

Tier I

Green algae 

(Pseudokirchneriella 

subcapitata)

5-day EC50: >1.1 mg/L

NOAEC: 1.1 mg/L

444577-76

Acceptable

Blue-green algae

(Anabaena flos-aquae)

5-day EC50: >1.2 mg/L

NOAEC: 1.2 mg/L

444577-78

Acceptable

Freshwater diatom

(Navicula pelliculosa)

5-day EC50: >1.2 mg/L

NOAEC: 1.2 mg/L

444577-79

Acceptable

Marine diatom

(Skeletonema costatum)

5-day EC50: >1.1 mg/L

NOAEC: 1.1 mg/L

444577-77

Acceptable

Aquatic – Vascular 

Plants

850.4400

Tier I

Duckweed 

(Lemna gibba)

14-day EC50: >1.2 mg/L

NOAEC: 0.12 mg/L

444577-80

Acceptable

4.2. Effects to Terrestrial Organisms

Table 4.2 summarizes the terrestrial toxicity data for prohexadione calcium based on an 

evaluation of submitted studies. In general, prohexadione calcium is practically non-toxic to 

birds on an acute basis. No effects were observed in either of the chronic avian reproduction 

studies. Prohexadione calcium is practically non-toxic to laboratory rats on an acute oral basis. In 
10

a two-generation reproductive toxicity study, parental systemic toxic effects were observed in the 

laboratory rat. Prohexadione calcium is practically non-toxic to honey bees. Tier I seedling 

emergence and vegetative vigor toxicity studies were conducted for terrestrial plants. While 

definitive EC25s were not observed in either study, signs of toxicity affecting as many as 23-24% 

of test organisms were observed. Due to the lack of establishment of NOAECs and that 

prohexadione calcium is a known phytotoxicant, Tier II studies conducted at a range of 

concentrations are necessary to determine NOAECs.

Table 4.2. Summary of the Endpoints from Submitted Terrestrial Toxicity Studies for 

Prohexadione calcium

Study Type Species Toxicity Value & Category MRID & Status

Acute – Avian Oral

850.2100

Bobwhite Quail 

(Colinus virginianus)

LD50: >2000 mg/kg-bw/day

Practically non-toxic

444577-23

Acceptable

Acute – Avian Oral

850.2100

Mallard Duck

(Anas platyrhynchos)

LD50: >2000 mg/kg-bw/day

Practically non-toxic

444577-24

Acceptable

Acute – Avian 

Dietary

850.2200

Bobwhite Quail 

(Colinus virginianus)

LC50: >5250 mg/kg-diet

Practically non-toxic

444577-25

Acceptable

Acute – Avian 

Dietary

850.2200

Mallard Duck

(Anas platyrhynchos)

LC50: >5250 mg/kg-diet

Practically non-toxic

444577-26

Acceptable

Chronic – Avian 

Reproduction

850.2300

Bobwhite Quail 

(Colinus virginianus)

NOAEC: 1000 mg/kg-diet

LOAEC: >1000 mg/kg-diet

(no effects)

444577-27

Acceptable

Chronic – Avian 

Reproduction

850.2300

Mallard Duck

(Anas platyrhynchos)

NOAEC: 1000 mg/kg-diet

LOAEC: >1000 mg/kg-diet

(no effects)

444577-28

Supplemental

(poor control performance)

Acute – Mammalian 

Oral

870.1100

Rat 

(Rattus norvegicus)

LD50: >5000 mg/kg-bw

Practically non-toxic

444577-42

Acceptable

Chronic –

Mammalian 

Reproduction

870.3800

Rat 

(Rattus norvegicus)

NOAEC: 35 mg/kg-diet

LOAEC: 385 mg/kg-diet

(based on parental systemic 

toxicity)

444577-64

Acceptable

444577-63

Acceptable

Acute – Contact 

Toxicity

850.3020

Honey Bee

(Apis mellifera)

LC50: >100 μg/bee

Practically non-toxic

444577-81

Acceptable

Acute - Oral Toxicity

Non-guideline

Honey Bee

(Apis mellifera)

LD50: >100 μg/bee 444577-81

Acceptable

Seedling Emergence

Tier I

850.4100

Most sensitive dicot: 

Lettuce

Most sensitive monocot: 

Ryegrass

EC25: > 1.7 lb a.i./A

(24% inhibition observed for 

lettuce and 17% inhibition 

observed for ryegrass based on dry 

weight)

NOAEC: < 1.7 lb a.i./A

444577-74

Supplemental 

(fertilizer and surfactant 

added to treatment groups 

but not control groups; no 

NOAEC established)

Vegetative Vigor

Tier I

850.4150

Most sensitive dicot: 

Cucumber

Most sensitive monocot: 

Ryegrass

EC25 > 1.7 lb a.i./A

(21% inhibition observed for 

cucumber and 23% inhibition 

observed for ryegrass based on 

height)

NOAEC: < 1.7 lb a.i./A

444577-75

Supplemental

(fertilizer and surfactant 

added to treatment groups 

but not control groups; no 

NOAEC established)
11

4.3. Incident Databases Review

Three databases, the Ecological Incident Information System or EIIS maintained by the 

Environmental Fate and Effects Division, the Aggregate Summary Module (ASM) of Office of 

Pesticide Program’s Incident database maintained by the Information Technology and Resource 

Management Division, and the Avian Incident Monitoring System (AIMS) maintained by the 

American Bird Conservancy, were searched on August 6, 2012 to locate incidents resulting from 

the use of prohexadione calcium. No incidents were reported in EIIS or AIMS. There were two 

minor plant incidents reported in the Aggregate Incident database (Appendix B). These incidents 

involved the product Apogee. One was reported to have occurred from July to October 2002, and 

the other occurred from June to September 2005. No other information regarding these incidents 

is available. It should be noted that a limited number of reported incidents should not be taken as 

an indicator of little or no ecological risk.

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 nationwide ecological risk assessment. 

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

field and immediately adjacent areas that may receive drift or runoff. Areas adjacent to the 

treated field 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 water bodies adjacent to or downstream from the 

treated field 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, as defined 

by an ecological entity (species, community, or other entity) and its attribute or characteristics 

(USEPA, 1998). For prohexadione calcium, the ecological entities may include the following: 

birds, mammals, terrestrial-phase amphibians, reptiles, freshwater fish and invertebrates, aquaticphase amphibians, estuarine/marine fish and invertebrates, terrestrial plants, terrestrial 

invertebrates, and aquatic plants. The attributes for each of these entities include survival, 

growth, and reproduction.

6. Conceptual Model

The conceptual model for prohexadione calcium provides a written description and visual 

representation of the predicted relationships between prohexadione calcium, potential routes of 

exposure, and the predicted effects for the assessment endpoints. A conceptual model consists of 

two major components: a risk hypothesis and a conceptual diagram (USEPA, 1998).
12

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.

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 prohexadione 

calcium, the following 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, prohexadione calcium has the potential to 

reduce survival, reproduction, and/or growth in non-target terrestrial and aquatic plants 

(due to the mode of action and lack of adequate data) and aquatic fish and invertebrates 

(due to lack of adequate chronic data for freshwater and estuarine/marine fish and 

estuarine/marine invertebrates) when used in accordance with the current labels. These 

non-target organisms include Federally-listed threatened and endangered species as well 

as non-listed species.

6.2. Conceptual Diagram

In addition to direct spray, the environmental fate properties of prohexadione calcium indicate 

that runoff and spray drift represent potential transport mechanisms of prohexadione calcium to 

aquatic and terrestrial habitats where non-target organisms may be exposed. These transport 

mechanisms are depicted in the conceptual models below (Figures 6.1, 6.2, and 6.3) along with 

the receptors of concern and the potential attribute changes in the receptors due to exposure to 

prohexadione calcium. 
13

Figure 6.1. Conceptual Model for Exposure and Effects of Prohexadione Calcium to 

Aquatic Organisms. Dotted Lines Indicate Exposure Pathways that Have a Low Likelihood 

of Contributing to Ecological Risk. 

**Route of exposure includes only ingestion of fish and aquatic invertebrates

Stressor

Source

Receptors

Attribute

Change

Prohexadione calcium applied to use site

Spray drift

Aquatic animals

Invertebrates 

Vertebrates

Piscivorous mammals 

 and birds** 

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae and 

 vascular plants

Reduction in prey

Modification of PCEs 

 related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to 

 habitat

Surface water/

Sediment

Runoff

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Uptake/gills 

or integument

Ingestion Ingestion

Atmospheric 

transport

Wet/dry deposition

Soil Leaching to

Groundwater

Uptake/gills 

or integument

Aquatic Plants

Non-vascular

Vascular

Uptake/cell, 

roots, leaves Riparian plants

terrestrial 

exposure 

pathways see 

Figure 6.2
14

Figure 6.2. Conceptual Model for Exposure and Effects of Prohexadione Calcium to 

Terrestrial Organisms. Dotted Lines Indicate Exposure Pathways that Have a Low 

Likelihood of Contributing to Ecological Risk.

Stressor

Source

Attribute

Change

Prohexadione calcium applied to use site

Direct

application Spray drift

Terrestrial 

vertebrates*

Terrestrial 

Inverts*

Individual 

organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in prey and 

food

Modification of PCEs 

 related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related

 to habitat

Terrestrial plants

grasses/forbs, fruit, seeds 

(trees, shrubs)

Runoff

Terrestrial 

vertebrates* 

Exposure Media 

& Receptors Soil

Ingestion

Ingestion

Dermal uptake/Ingestion

Atmospheric 

transport

Root uptake/contact

Wet/dry deposition

Ingestion

Leaching to

Groundwater

Irrigation 

water

* See Figure 6.3 for drinking water and inhalation exposure pathways for terrestrial vertebrates and ingestion of residues in dew by 

terrestrial invertebrates. 
15

Figure 6.3. Conceptual Model for Drinking Water and Inhalation Exposure Pathways for 

Terrestrial Vertebrates and Ingestion of Residues in Dew by Terrestrial Invertebrates. 

Dotted Lines Indicate Exposure Pathways that Have a Low Likelihood of Contributing to 

Ecological Risk. 

7. Analysis Plan

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

be estimated. The use, environmental fate, and ecological effects of prohexadione calcium will 

be characterized and integrated to assess the risks. 

This analysis plan will be revisited and may be revised depending upon a full review of 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

The major transformation product of prohexadione calcium is despropionyl, which degrades 

further into tricarballylic acid and citric acid. Both tricarballylic acid and citric acid are naturally 

occurring substances. Currently, there are no known toxicological concerns associated with 

Stressor

Source

Attribute

Change

Prohexadione calcium applied to use site

Direct

application Spray drift

Terrestrial 

vertebrates

Terrestrial 

invertebrates

Individual 

organisms

Reduced survival

Reduced growth

Reduced 

reproduction

Food chain

Reduction in prey and 

food

Modification of PCEs 

 related to prey 

availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related

 to habitat

Runoff

Exposure Media Dew (formed on 

terrestrial plants)

Atmospheric 

transport

Receptors

Puddles (formed 

on treated fields)

Inhalation Imbibition

Air
16

prohexadione calcium transformation products. Therefore, only the parent compound 

prohexadione calcium will be considered. 

The Agency does not routinely include, in its risk assessments, 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 multiple 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, they may be used qualitatively or quantitatively in 

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

(USEPA, 2004; USFWS/NMFS, 2004).

7.2. Measures of Exposure

In order to estimate risks of prohexadione calcium exposures in aquatic and terrestrial 

environments, all exposure modeling and resulting risk conclusions will be based on registered 

labels including maximum application rates and methods cited in Table 3.3 for each use of 

prohexadione calcium. EFED’s environmental exposure models estimate the potential exposure 

of plants and animals to pesticide residues in aquatic and terrestrial environments. Some of the 

aquatic models can also be utilized to estimate pesticide residues in drinking water for use in the 

dietary exposure models. A more detailed description of aquatic and terrestrial models can be 

found at the following website: http://www.epa.gov/pesticides/science/models_db.htm. For 

terrestrial exposures, the default 35-day foliar dissipation half-life will be used. If RQs exceed 

LOCs, the foliar dissipation half-life may be refined, as appropriate, using available magnitude 

of residue studies at the time of the risk assessment. 

In addition to modeling estimates, available monitoring data will be evaluated. Monitoring data 

will include those collected/reported by states as well as other federal departments/agencies (e.g., 

USGS National Water Quality Assessment; http://water.usgs.gov/nawqa). These monitoring data 

will be characterized in terms of general statistics including number of samples, frequency of 

detection, maximum concentration, and mean value of all detections, where that level of detail is 

available.

The Screening Imbibition Program (SIP v.1.0) is used during the problem formulation phase of 

Registration Review to provide an upper-bound estimate of exposure of birds and mammals to 

pesticides through drinking water alone. SIP does not aggregate the drinking water exposure 

route with other exposure routes (i.e., dietary, inhalation, dermal). Because avian and 

mammalian acute toxicity values were non-definitive, SIP was not used, and it is assumed that 

acute and chronic exposure through drinking water alone would not be a concern for birds and 

mammals.

The Screening Tool for Inhalation Risk (STIR v.1.0) is used during the problem formulation 

phase of Registration Review to assess the potential for exposure to birds and mammals through 

inhalation. The exposure pathways that are assessed by this tool include both droplet inhalation 
17

and vapor phase inhalation. STIR is intended to determine if exposure is likely and not whether 

or not the potential for risk exists. If STIR predicts that exposure is likely, additional inhalation 

data may be necessary to adequately assess risk due to the inhalation exposure pathway. Because 

avian and mammalian acute toxicity values were non-definitive, STIR was not used, and it is 

assumed that exposure through inhalation would not be a concern for birds and mammals (acute 

rat inhalation LC50 > 4.21 mg/L; MRID 444577-44). 

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 open literature studies identified by

ECOTOX. The ECOTOX database 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 EPA’s Office of Research and Development and the National 

Health and Environmental Effects Research Laboratory's Mid-Continent Ecology Division 

(USEPA, 2009a).

Where available, sub-lethal 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 prohexadione calcium to birds is similar to terrestrial-phase amphibians and reptiles. 

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

7.4. Integration of Exposure and Effects

For the assessment of prohexadione calcium risks, the risk quotient (RQ) method will be used to 

compare exposure and measured toxicity values. EECs will be divided by acute and chronic 

toxicity values. The resulting RQs will then be compared to the Agency’s Levels of Concern 

(LOCs). In addition, other lines of evidence, such as reported incidents, will be considered. 

These criteria are used to indicate when the use of prohexadione calcium, as directed on labels, 

has the potential to cause adverse direct or indirect effects to non-target organisms.

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. Depending on the risk manager’s need for 

additional information regarding risk, an effort may be made to further describe risk using 

probabilistic tools that the Agency has developed. These tools have been reviewed by FIFRA 
18

Scientific Advisory Panels6and have been deemed as appropriate means of refining assessments 

where deterministic approaches have identified risks.

7.6. Endangered Species Assessment

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 prohexadione calcium. This assessment will be conducted in accordance with 

the Overview Document (USEPA, 2004), provisions of ESA, and the Services’ Endangered 

Species Consultation Handbook (USFWS/NMFS, 1998).

7.7. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), prohexadione calcium is

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. Prohexadione calcium is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of Registration Review, EPA will issue future EDSP orders/data 

call-ins, requiring the submission of EDSP screening assays for prohexadione calcium. For 

 

6

http://www.epa.gov/scipoly/sap/index.htm
19

further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/.

7.8. Human Health Drinking Water Assessment

A drinking water assessment will be conducted to support future human health dietary risk 

assessments of prohexadione calcium. The drinking water assessment will incorporate model 

estimates of prohexadione calcium and any major degradates of concern in surface water and 

ground water. Concentrations of prohexadione calcium residues in surface waters will be 

estimated using PRZM/EXAMS. Percent Cropped Area (PCA) adjustment factors will be used to 

account for the maximum fractional area within a watershed that may be planted with a modeled 

crop, and are used to modify drinking water concentrations predicted by PRZM and EXAMS 

(http://www.epa.gov/oppefed1/models/water/pca_adjustment_dwa.html).

An Estimated Drinking Water Concentration (EDWC) of prohexadione calcium residues in 

ground water will be estimated using EFED’s Tier I aquatic model SCI-GROW (Screening 

Concentration in Ground Water). SCI-GROW is a regression model used as a screening tool to 

estimate pesticide concentrations found in ground water used as drinking water. Alternatively, 

the Tier II PRZM-GW (groundwater) Model may be used if it is approved for use at the time of 

the risk assessment.

7.9. Preliminary Identification of Data Gaps

According to the Code of Federal Regulations 40 (CFR40 2007) Part 158 Subpart D (data 

requirements for pesticides), environmental fate and non-target organism effects data are 

required for prohexadione calcium based on its terrestrial use patterns. Available studies 

submitted to fulfill environmental fate and ecological effects guideline requirements, as well as 

outstanding data gaps for prohexadione calcium, are defined in Sections 7.9.1 and 7.9.2.

7.9.1. Fate Data Gaps

Table 7.1 lists the status of the fate and transport data requirements for prohexadione calcium. 

The fate database for prohexadione calcium is complete (with the exception of the leaching,

anaerobic soil metabolism, and aerobic aquatic metabolism studies noted below, which are not 

recommended for request at this time). No additional studies are recommended for request at this 

time. However, it is noted that several fate studies were submitted to the EU for prohexadione 

calcium. For harmonization purposes, it would be helpful for these studies to be formally 

submitted to EPA also. These studies are noted in the comments column of Table 7.1.
20

Table 7.1. Status of Available Environmental Fate Data for Prohexadione Calcium and 

Remaining Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

835.2120

161-1

Hydrolysis 44457782 Acceptable No

A different hydrolysis study was 

submitted for registration in the EU. For 

harmonization purposes, it would be 

helpful for this study to be formally 

submitted to EPA also. 

Hoefs R. 2008. Hydrolysis of 14C-BAS 

125 W (Prohexadione-Calcium). BASF 

SA; Guaratingueta; Brazil. 

2008/1028622

835.2240

161-2

Photodegradation in Water

44457783 Acceptable No

A modeling study of photolysis in water

was submitted for registration in the 

EU. For harmonization purposes, it 

would be helpful for this study to be 

formally submitted to EPA also. 

Callow B., Jarvis T. 2008. 

Determination of rates of decline for 

Prohexadione Calcium and its 

metabolites from the aqueous photolysis 

study (BASF DocID 1996/5216) 

according to the guidance within the 

FOCUS Kinetics Guidance Document. 

Exponent International Ltd.; Harrogate 

North Yorkshire HG2 8RE; United 

Kingdom. 2008/1042830

835.2410

161-3

Photodegradation in Soil

44457784 Marginally 

Acceptable No

A modeling study of photolysis in soil

was submitted for registration in the 

EU. For harmonization purposes, it 

would be helpful for this study to be 

formally submitted to EPA also. 

Callow B., Jarvis T. 2008. 

Determination of rates of decline for 

Prohexadione-Calcium and its 

metabolites from the soil photolysis 

study (BASF DocID 1995/5187) 

according to the guidance within the 

FOCUS Kinetics guidance document. 

Exponent International Ltd.; Harrogate 

North Yorkshire HG2 8RE; United 

Kingdom. 2008/1042832

835.2370

161-4

Photodegradation in Air -- Not Required No --
21

Table 7.1. Status of Available Environmental Fate Data for Prohexadione Calcium and 

Remaining Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

835.4100

162-1

Aerobic 

Soil 

Metabolism

44457785 Acceptable No

A modeling study of aerobic soil 

metabolism was submitted for 

registration in the EU. For 

harmonization purposes, it would be 

helpful for this study to be formally 

submitted to EPA also. 

Callow B., Jarvis T. 2008. 

Determination of rates of decline for 

Prohexadione-Calcium from the soil 

metabolism study (BASF DocID 

1993/10256) according to the guidance 

within the FOCUS Kinetics guidance 

document. Exponent International Ltd.; 

Harrogate North Yorkshire HG2 8RE; 

United Kingdom. 2008/1042834.

835.4200

162-2

Anaerobic 

Soil 

Metabolism

-- -- Yes

An anaerobic soil metabolism study 

was submitted for registration in the 

EU. For harmonization purposes, it 

would be helpful for this study to be 

formally submitted to EPA also. 

O Connor J. 1993. BX-112: Anaerobic 

soil degradation study. Pharmaco LSR 

Ltd.; Eye Suffolk IP23 7PX; United 

Kingdom. 1993/10767.

835.4300

162-4

Aerobic 

Aquatic 

Metabolism

-- -- Yes

Either an aerobic aquatic metabolism 

study or a different anaerobic aquatic 

metabolism study was submitted for 

registration in the EU. Again for 

harmonization purposes, it would be 

helpful for the aquatic metabolism 

study to be formally submitted to 

USEPA also. 

OConnor J. 1994. BX-112: BBA plant 

protection product evaluation: 

Degradation and retention of pesticides 

in the water/sediment system (Guideline 

IV, 5-1). Pharmaco LSR Ltd.; Eye 

Suffolk IP23 7PX; United Kingdom. 

1994/10949.

835.4400

162-3

Anaerobic 

Aquatic 

Metabolism

44457786 Supplemental No
22

Table 7.1. Status of Available Environmental Fate Data for Prohexadione Calcium and 

Remaining Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

835.1230

835.1240

163-1

LeachingAdsorption/ 

Desorption

44457787

44457788

44457789

44457790

Acceptable

Invalid

Invalid

Invalid

No

Yes

Yes

Yes

A soil column study was submitted for 

registration in the EU that appears to be 

different from the studies submitted to 

the USEPA. For harmonization 

purposes, it would be helpful for this 

study to be formally submitted to 

USEPA also. 

O Connor J. 1993. BX-112: BBA plant 

protection product evaluation: 

Determination of the seepage behaviour 

of BX-112 by soil column studies 

(normal test). Life Science Research 

Ltd.; Eye Suffolk IP23 7PX; United 

Kingdom. 1993/10218

835.1410

163-2

Laboratory 

Volatility -- Not Required No --

835.8100

163-3

Field Volatility -- Not Required No --

835.6100

164-1

Terrestrial 

Field 

Dissipation

44457791

44725213

Marginally 

Acceptable

Marginally 

Acceptable

No

No

--

Analytical 

Method - Soil

44725214

44725215

45040301

Acceptable

Acceptable

Acceptable

No

No

No

--

Analytical 

Method - Water 45062301 Acceptable No

Analytical --

MethodSediment45062301 Acceptable No

835.6200

164-2

Aquatic 

Field 

Dissipation

-- Not Required No --

835.6300

164-3

Forestry field 

Dissipation 

Study

-- Not Required No --

850.1730

165-4

Accumulation 

in fish

-- Not Required No --

165-5

Accumulationaquatic nontarget

-- Not Required No --

835.7100

166-1

Ground Watersmall 

prospective

-- Not Required No --
23

Table 7.1. Status of Available Environmental Fate Data for Prohexadione Calcium and 

Remaining Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

166-2

Ground Watersmall 

retrospective

-- Not Required No --

201-1

Droplet Size 

Spectrum

-- Not Required No --

202-1

Drift Field 

Evaluation

-- Not Required No --

7.9.2. Effects Data Gaps

Many submissions have been made to provide data on the effects of prohexadione calcium to 

aquatic and terrestrial organisms. Data gaps are included in Tables 7.2 to 7.4, below.

Table 7.2. Available Ecological Effects Data for Terrestrial Animals Exposed to Prohexadione 

Calcium and Remaining Data Gaps

Guideline Description MRID Classification

Data Gap

According 

to 40 CFR 

Part 158?

Additional Data Recommended 

for Request?

(Risk Management 

Recommendations)

850.2100 Avian oral toxicity

444577-23 Acceptable

Yes

Yes. Acceptable avian data were 

submitted for the bobwhite quail, 

mallard duck, and pheasant. 

However, avian acute oral 

toxicity data are not available for 

passerines, which are required 

under 40 CFR Part 158.Passerine 

birds may utilize metabolic 

pathways that are different from 

larger birds. In addition, 

estimated environmental doses 

are not expected to be at least 10 

times lower than the highest dose 

tested. 

444577-24 Acceptable

850.2200 Avian dietary toxicity

444577-25 Acceptable

No

--

444577-26 Acceptable --

850.2300 Avian reproduction 444577-27 Acceptable No --
24

Table 7.2. Available Ecological Effects Data for Terrestrial Animals Exposed to Prohexadione 

Calcium and Remaining Data Gaps

Guideline Description MRID Classification

Data Gap

According 

to 40 CFR 

Part 158?

Additional Data Recommended 

for Request?

(Risk Management 

Recommendations)

444577-28 Supplemental Yes

No. Low overall hatching success 

was observed in the control 

group. In addition, the dietarybased EEC for short grass (527.36 

ppm) in the most recent risk 

assessment (DP 384104; April 11, 

2011) overlaps concentrations 

tested in the study. However, no 

effects were observed in the quail 

reproduction study, where control 

performance was not an issue. 

There was no difference in 

toxicity between bobwhite quail 

and mallard duck in acute oral or 

subacute dietary studies (no 

effects observed). Therefore, 

submission of a new mallard 

reproduction study is not likely to 

change risk conclusions.

850.3020 Honeybee acute 

contact toxicity 444577-81 Acceptable No --

870.1100 Mammalian oral 

toxicity 444577-42 Acceptable No --

870.3800 Mammalian 

reproduction toxicity

444577-63

444577-64 Acceptable No --

Mammalian inhalation 

toxicity Acceptable No --

Table 7.3. Available Ecological Effects Data for Aquatic Animals Exposed to 

Prohexadione Calcium and Remaining Data Gaps

Guideline Description MRID Classification

Data Gap

According 

to 40 CFR 

Part 158?

Additional Data 

Recommended for Request?

(Risk Management 

Recommendations)

850.1075 Freshwater fish –

Acute toxicity 

444577-30

Coldwater Supplemental Yes

No. While acceptable data are 

generally required, the studies 

were classified as supplemental 

because the mean measured 

limit concentrations tested were 

94.6 mg a.i./L for the rainbow 

trout and 95.6 mg a.i./L for the 
25

Table 7.3. Available Ecological Effects Data for Aquatic Animals Exposed to 

Prohexadione Calcium and Remaining Data Gaps

Guideline Description MRID Classification

Data Gap

According 

to 40 CFR 

Part 158?

Additional Data 

Recommended for Request?

(Risk Management 

Recommendations)

444577-29

Warmwater Supplemental

bluegill sunfish rather than the 

required 100 mg a.i./L. 

However, no fish died in either 

study and no sublethal effects 

were observed. Therefore, it is 

not likely that a definitive LC50

would be obtained by repeating 

the study at a slightly increased 

concentration. 

850.1075 Estuarine/marine fish –

Acute toxicity 444577-32 Acceptable No --

850.1010

Freshwater 

invertebrates –

Acute toxicity

444577-31 Acceptable No --

850.1025

850.1035

Estuarine/marine

invertebrates –

Acute toxicity 

444577-33 Acceptable No --

444577-34 Supplemental Yes No, if the age of the mysids 

tested can be reported. 

850.1400 Freshwater fish –

early life stage test

Not 

submitted Not applicable Yes Yes. Acceptable data are required for the use patterns. 

850.1400 Estuarine/marine fish –

early life stage test

Not 

submitted Not applicable Yes

No. While acceptable data are 

required for the use patterns, 

pending receipt and review of an 

acceptable freshwater fish earlylife stage study (bluegill sunfish 

or rainbow trout), the acute-tochronic ratio (or similar 

comparison in the case of nondefinitive endpoints) can be 

used to predict chronic toxicity 

to estuarine/marine fish. 

850.1300

Freshwater 

invertebrate –

life cycle test

444577-35 Supplemental Yes

Yes. Growth measurements 

were not reported. Therefore, 

the study endpoints are based on 

reproduction only (no significant 

mortality was observed).
26

Table 7.3. Available Ecological Effects Data for Aquatic Animals Exposed to 

Prohexadione Calcium and Remaining Data Gaps

Guideline Description MRID Classification

Data Gap

According 

to 40 CFR 

Part 158?

Additional Data 

Recommended for Request?

(Risk Management 

Recommendations)

850.1350

Estuarine/marine 

invertebrates –

life cycle test

Not 

submitted Not applicable Yes

No. While acceptable data are 

required for the use patterns, 

pending receipt and review of an 

acceptable freshwater 

invertebrate life cycle study 

(daphnid) and age of the mysids 

in the acute estuarine/marine 

invertebrate study, the acute-tochronic ratio (or similar 

comparison in the case of nondefinitive endpoints) can be

used to predict chronic toxicity 

to estuarine/marine 

invertebrates.

Table 7.4. Available Ecological Effects Data for Plants Exposed to Prohexadione Calcium 

and Remaining Data Gaps

Guideline Description MRID Classification

Data Gap

According 

to 40 CFR 

Part 158?

Additional Data 

Recommended for Request?

(Risk Management 

Recommendations)

850.4100

Terrestrial Plant 

toxicity: Tier I 

seedling emergence

444577-74 Supplemental

Yes

Yes. Tier II studies are 

needed to determine 

NOAECs since prohexadione 

calcium is a known 

phytotoxicant. While EC25s 

were non-definitive in the 

Tier I studies, effects were 

observed at the limit 

concentration. In addition, 

fertilizers and surfactants 

were added to treatment 

groups but not control groups, 

which affects the scientific 

validity of the study. 

850.4150

Terrestrial Plant 

toxicity: Tier I 

vegetative vigor

444577-75 Supplemental

850.5400 Aquatic Plant Growth: 

algae

444577-76

444577-78

444577-79

444577-77

Acceptable No --

850.4400 Aquatic Plant Growth: 

vascular plants 444577-80 Acceptable No --
27

8. References

USEPA. 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

USEPA. 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.

USEPA. 2009a. ECOTOXicology Database, United States Environmental Protection Agency 

(USEPA). Available at http://cfpub.epa.gov/ecotox/.

USEPA. 2012a. Prohexadione (112600): Screening Level Usage Analysis (SLUA). Biological 

and Economic Analysis Division, Office of Pesticide Programs. March 30, 2012

USEPA. 2012b. Prohexadione (112600): EFED Label Data Report. Biological and Economic 

Analysis Division, Office of Pesticide Programs. May 25, 2012

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.
28

Appendix A. Chemical Structures of Prohexadione Calcium and Its Degradates

Table A-1. Chemical Names and Structures of Prohexadione Calcium and Its 

Degradates

Chemical Name Structure

Cyclohexanecarboxylic acid, 3,5-dioxo4-(1-oxopropyl)-, ion (1-), calcium,

calcium salt

(Prohexadione calcium)

BASF Code Numbers: BAS 125 W, 

BAS 9054 W

Kumiai Code Numbers: KIM-H2, BX1l2, KUH-833

Prohexadione (this is the fully 

protonated [non-ionic] form)

3-Hydroy-5-oxo-3-cyclohexene-1-

carboxylic acid

(Despropionyl Prohexadione or BW 

9054-5376)

BX-112-M-10

Tricarballylic acid

C

O

OO

-O

C

O

H2C

H3C

Ca2+

C

O

OH

O

O

C

O

H2C

H3C

C

O

OH

HO

O

C

O

OH

O

O

HO

H3C

C

O

OH

O

O

HO

HO
29

Table A-1. Chemical Names and Structures of Prohexadione Calcium and Its 

Degradates

Chemical Name Structure

Citric acid

C

O

OH

O

O

HO

HO

HO
30

Appendix B. Prohexadione Calcium Incidents

Aggregate Incident Report for EFED

Prohexadione calcium

PC Code: 112600

Total Count of Minor Incidents from Aggregated Reports

Minor Fish and Wildlife Incidents (W-B): 0

Minor Plant Incidents (P-B): 2

Minor "Other Nontarget" Incidents (ONT): 0

Date Range Package Page Product Sum W-B P-B ONT

7/1/2002 - 10/1/2002 013492 2 APOGEE 1 0 1 0

6/1/2005 - 9/1/2005 016919 3 APOGEE 1 0 1 0

Data in this report are derived from the Aggregate Summary Module of OPP's Incident Database, maintained by 

the Information Services Branch of the Information Technology and Resource Management Division.

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