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.

                                     				
                                       
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
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
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
                                  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.

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
                                     NS[3]

                                     A[1]
                                    0.61875
                                   NS (2.75)
                                    1.70156
                                     NS[3]
Cherry
                                       G
                                    0.34375
                                    NS (2)
                                    0.68750
                                     NS[3]

                                     A[1]
                                    0.34375
                                    NS (2)
                                    0.68750
                                     NS[3]
Peanuts
                                     G[2]
                                    0.12525
                                    NS (3)
                                     0.375
                                     NS[5]
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
                                  NS[4] (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
                                  NS[4] (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 30[th], 2012 (current as of 5/25/12):
  [1]Not allowed in California
  [2]Allowed in Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, North Carolina, New Mexico, Oklahoma, South Carolina, Texas, Virginia
  [3]Application intervals not specified on Apogee Plant Growth Regulator label (7969-188).
  [4]Maximum number of applications per year not specified on GWN-6010 label (10163-315).
  [5]Application 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 x 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
                                       
MRID 44457702
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
PPDB[1]
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 x 10[-6])
MRID 44457713
Vapor Pressure (25[o]C)
1.737 x 10-5 Pa (1.303 x 10[-7] mm Hg)
MRID 44457712
Water Solubility (20[o]C)
174.2 mg/L @ 20[o]C
MRID 44457709
Octanol-Water Coefficient( Log Kow )
-2.90 @20[o]C (KOW = 1.25 x 10[-3])
MRID 44457713
Henry's Law Constant at 25[o]C
2.595 x 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 (T(1/2) = 1.4 days). It degrades slowly under anaerobic conditions (T(1/2) = 117 days in anaerobic aquatic metabolism study). It is subject to rapid hydrolysis under acidic conditions (T(1/2) (pH 5) = 4.4 days) but is resistant to hydrolysis in higher pH environments (T(1/2) (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 (T(1/2))
                                4.4 days @ pH 5
                                65 days @ pH 7
                                 Stable @ pH 9
Despropionyl  -  92% (28 days @ pH 5)
                                   44457782
                                  Acceptable
Direct Aqueous Photolysis (T(1/2))
                               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
Soil Photolysis (T(1/2)) 
                                   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 (T(1/2))
                     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 (T(1/2))
                              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 (T(1/2)) (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.
                                  44457791[2]
                                  Acceptable

                                 15 days (NY)
                                 20 days (CA)
                                 5.7 days (OR)

                                  44725213[3]
                                  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 Kf is 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 (r[2] = 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 (T(1/2)) obtained following two treatments of 2.0 lb a.i./acre with prohexadione calcium (BAS 125 W) broadcast at 14 day intervals.

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 Act.  In addition, no Total Maximum Daily Loads (TMDL) have been developed for the plant growth regulator. The Impaired Waters and Total Maximum Daily Loads website can be consulted for more information. The Agency invites submission of water quality data for this pesticide.  To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP's Registration Review Risk Assessment and Management Process, 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) database, 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. 

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  -  Non-vascular 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 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 ug/bee
                             Practically non-toxic
                                   444577-81
                                  Acceptable
                             Acute - Oral Toxicity
                                 Non-guideline
                                   Honey Bee
                               (Apis mellifera)
                             LD50: >100 ug/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)
      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, aquatic-phase 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).

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.  

**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
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. 

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. 
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 
                                 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)
Imbibition
Inhalation
                                      Air

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 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 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 Scientific Advisory Panels and 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 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.

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
Photodegrada-tion 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
Photodegrada-tion 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
Photodegrada-tion in Air
                                      --
                                 Not Required
                                      No
                                      --
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

835.1230
835.1240
163-1
Leaching-Adsorption/ 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 Method- Sediment
                                   45062301
                                  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
Accumulation- aquatic non-target
                                      --
                                 Not Required
                                      No
                                      --
835.7100
166-1
Ground Water- small prospective
                                      --
                                 Not Required
                                      No
                                      --
166-2
Ground Water- small 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
                                      --
                                       
                                       
                                   444577-28
                                 Supplemental
                                      Yes
No. Low overall hatching success was observed in the control group. In addition, the dietary-based 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 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. 
                                       
                                       
                                   444577-29
                                   Warmwater
                                 Supplemental
                                       
                                       
                                   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 early-life stage study (bluegill sunfish or rainbow trout), the acute-to-chronic ratio (or similar comparison in the case of non-definitive 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).
                                   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-to-chronic ratio (or similar comparison in the case of non-definitive 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
                                      --

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.
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-dioxo-4-(1-oxopropyl)-, ion (1-), calcium, calcium salt
(Prohexadione calcium)

BASF Code Numbers: BAS 125 W, BAS 9054 W
Kumiai Code Numbers: KIM-H2, BX-1l2, 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
                                       
Citric acid
                                       


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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