### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHI NGTON , 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 Wey rauch, 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 currentl y known about the environmental fate and ecological effects associated with prohexadione calcium and its degradates. It also describes the preliminary ecological risk hy

pothesis and anal ys is plan for evaluating and characterizing drinking water exposure and risk to non - target species and th e 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 c alcium.

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# 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 Ave** **nue , NW**  **Mail Code 7507P Washington, DC 20460**  **Reviewed by:** Robin Sternberg , Ph.D., Wildlife Biologist He Zhong , Ph.D., Biologist **November 20 , 2012**  C OOO

-O C O H 2 C H 3 C Ca2+

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**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 Hy

pothesis ................................ ................................ ................................ ................. 12 6.2. Conceptual Diagram ................................ ................................ ................................ ......... 12 7. Analysis Plan ................................ ................................ ................................ ........................... 15 7.1. Stressor s 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

I dentification of Data Gaps ................................ ................................ ........... 19 7.9.1. Fate Data Gaps ................................ ................................ ................................ ........... 19 7.9.2. Ef fects Data Gaps ................................ ................................ ................................ ...... 23 8. References ................................ ................................ ................................ ................................ 27 Appendix A. Chemical Structures of Prohexadione Calcium and Its Degradates .................... 28 Appendix B. Prohexadione Calcium Incidents ................................ ................................ ......... 30

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**1. Purpose** This document will provide a plan for anal yz ing 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 characteri zing 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 Protec tion 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 o f 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 assess ment 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, a s well as risk s to terrestrial and semi - aquatic plants. **Table 2. 1**  **. Summary of Previous Ecological Risk and Drinking W**  **a ter A**  **ssessments 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 Prohexad ione 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

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**Table 2. 1**  **. Summary of Previous Ecological Risk and Drinking W**  **a ter A**  **ssessments 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 b y inhibiting th e biosy

nthesis of gibberellin. Inhibition of gibberellin results in reduction of shoot growth in plants. Prohexadi one 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 o f prohexadione calcium on agricultural crops (USEPA, 2012 a). Apples were the onl y crop reported , with estimated usage of 10,000 lb a.i. per ye ar. The average crop area treated was 10 % , with the maximum being 25 % . BEAD also provided a use characterization in the form of a L abel Data Report (USEPA, 2012 b ). **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), recreatio n area lawns, and residential lawns.

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**Table 3.1 . Maximum Labeled Application Rates for Prohexadione Calcium Uses**  **Use Site Application** 

**Me thod**  **Maximum Single**

**Application Rate**  **(lb a.i./acre) Number of** 

**Application s**  **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) 0.6875 0 NS 3 A 1 0.34375 NS (2) 0.6875 0 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 0.0300 8 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 0.7493 8 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 L abel U se Information S ystem report of May 30 th , 2012 (current as of 5/25/12) : 1 Not allowed in California 2Allowed in Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, North Carolina, New Mexico, Oklahoma, South Carolina, Texas, Virginia 3 Application intervals not specifie d on Apogee Plant Growth Regulator label (7969 - 188). 4 Maximum n

umber of application s 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 × 10 - 3 

### ), and not expected to volatilize from soil and water surfaces. **Table 3.2 .**  **Summary of Prohexadione C alcium Physical and Chemical Properties**  **Physical/Chemical Property Value (unit)**  **Source**

Chemical Structure MRID 44457702 C OOO

-O C O H 2 C H 3 C Ca2+

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**Table 3.2 .**  **Summary of Prohexadione C alcium 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 C 10 H 10 O 2 Ca MRID 44457702 Molecular Weight 250.27 g/mole MRID 44457702 S MILES 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 Phy sical State Tan colored, extruded solid MRID 44457721 Density or Specific gravity (23.7 o C) 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 (25 o C) 1.737 × 10 - 5 Pa (1.303 × 10 - 7 mm Hg) MRID 4445771 2 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 × 10 - 3 ) MRID 44457713 Henry’s Law Constant at 25 o C 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 ( T 1⁄2 

### = 1.4 days). It degrades slowl y under anaerobic conditions (T 1⁄2 

### = 117 days in anaerobic aquatic metabolism study). It is sub ject to rapid hydrolysis under acidic conditions ( T1⁄2 (pH 5) = 4.4 day s) but is resistant to hydrolysis in higher pH environments ( T 1⁄2 

### (pH 7) = 65 day s). 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** Hydroly sis (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) Com

bination 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

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**Table 3. 3**  **. Summary of Prohexadione calcium Environmental Fate Properties Study**  **Value Major Degradates**  **Minor Degradates MRID #**  **Study Status** Soil Photolysis (T 1⁄2) 32.4 days Despropionyl

– 15.21% (7 days) Bound Residues

– 10.28% (10 days) CO 2 – 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 Una cceptable

Aerobic Soil Metabolism (T 1⁄2) 1.4 days in sandy

loam soil at 25 °C Bound Residues

– 14.64% (5 days)

CO 2 – 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) CO 2 – 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 (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 (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.

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**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 1 

### . 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 information 3 

### . 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 Opera ting Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 4 

### , in order to ensure they can be used quantitatively or qualitatively

in pesticide risk assessments. **4. Recep tors**  Consistent with the process described in the Overview Document (USEPA, 2004), the risk assessment for prohexadione calcium will rel y on a surrogate species approach. Acute and chronic toxicity

data from studies submitted by pesticide registrants alon g 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 5 

### , 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** . Ingeneral, 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 earl y- 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 2http://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

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**Table 4.1. Summary of the Endpoints from Submitted Aquatic Toxicity Studies for**  **Prohexadione C**  **alcium Study Type**  **Species Toxicity Value**  **& Category MRID & Status**  Ac ute

– Freshwater Fish 850.1075 Rainbow trout

(Oncorhynchus mykiss ) 96 - hr LC 50 : >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) Ac ute

– Freshwater Fish 850.1075 Bluegill sunfish

( Lepomis macrochirus ) 96 - hr LC 50 : >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) Ac ute

– Estuarine/Marine Fish 850.1075 Sheepshead minnow

(Cyprinodon variegatus ) 96 - hr LC 50 : >122 mg/L Practically non - toxic 444577 - 32 Acceptable Ac ute

– Freshwater Invertebrate 850.1010 Water flea

( Daphnia magna ) 48 - hr EC 50 : >100 mg/L Practically non - toxic 444577 - 31 Acceptable Ac ute

– Estuarine/Marine Invertebrate 850.1025 Eastern oyster

( Crassostrea virginica ) 96 - hr E C 50 : >117 mg/L Practically non - toxic 444577 - 33 Acceptable Ac ute

– Estuarine/Marine Invertebrate 850.1035 My sid shrimp

( Americamysis bahia ) 96 - hr LC 50 : >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 (grow th of organisms was not measured) Aquatic

– Non vascular Plants 850. 45 00 & 850.4550 Tier I Green algae

(Pseudokirchneriella subcapitata ) 5 - day EC 50 : >1.1 mg/L NOAEC: 1 .1 mg/L 444577 - 76 Acceptable Blue - green algae ( Anabaena flos - aquae ) 5 - day EC 50 : >1.2 mg/L NOAEC: 1.2 mg/L 444577 - 78 Acceptable Freshwater diatom ( Navicula pelliculosa ) 5 - day EC 50 : >1.2 mg/L NOAEC: 1 .2 mg/L 444577 - 79 Acceptable Marine diatom (Skeletonema costatum ) 5 - day EC 50 : >1.1 mg/L NOAEC: 1.1 mg/L 444577 - 77 Acceptable Aquatic

– Vascular Plants 850.4400 Tier I Duckweed

( Lemna gibba ) 14 - day EC 50 : >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. Ingeneral, 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 practicall y non - toxic to laboratory rats on an acute oral basis. In

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

rat. Prohexadione calcium is practi cally non - toxic to honey

bees. Tier I seedling emergence and vegetative vigor toxicity studies were conducted for terrestrial plants. While definitive EC 25 

### s 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 phy totoxicant, 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** Ac ute

– Avian Oral 850.2100 Bobwhite Quail

(Colinus virginianus ) LD 50 : >2000 mg/kg -bw /day Practically non - toxic 444577 - 23 Acceptable Ac ute

– Avian Oral 850.2100 Mallard Duck

( Anas platyrhynchos ) LD 50 : >2000 mg/kg -bw /day Practically non - toxic 444577 - 24 Acceptable Ac ute

– Avian Dietary 850.2200 Bobwhite Quail

(Colinus virginianus ) LC 50 : >5250 mg/kg - diet Practically non - toxic 444577 - 25 Acceptable Ac ute

– Avian Dietary 850.2200 Mallard Duck

( Anas platyrhynchos ) LC 50 : >525 0 mg/kg - diet Practically non - toxic 444577 - 26 Acceptable Chronic

– Avian Reproduction 850.2300 Bobwhite Quail

(Colinus virginianus ) NOAEC: 10 00 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) Ac ute

– Mammalian Oral 870.1100 Rat

(Rattus norvegicus ) LD 50 : >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 Ac ute

– Contact Toxicity 850.3020 Honey Bee

( Apis mellifera ) L C 50 : >100 μg/bee Practically non - toxic 444577 - 81 Acceptable Ac ute - Oral Toxicity Non - guideline Honey Bee ( Apis mellifera ) LD 50 : >100 μg/bee 444577 - 81 Acceptable Seedling Emergence Tier I 850.4100 Most sensitive dicot: Lettuce Most sensitive monocot: Ryegrass EC 25 : > 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 EC 25 > 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)

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**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 Inform ation 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 ecos ys tems at risk are often extensive in scope; therefore, it may not be possible to identify specific ecos ys tems during the development of a nationwide ecological risk assessment. However, in general terms, terrestrial ecos ys tems potentially at risk could include the treated field and immediatel y adjacent areas that may receive drift or runoff. Areas adjacent to th e treated field could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats, and other uncultivated areas. Aquatic ecos ys tems 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 ecos ys tems, including estuaries. **5. Asses sm**  **ent 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 relations hips 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 hy pothesis and a conceptual diagram (USEPA, 1998).

### 12

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologicall y 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 comp lete, 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 hy pothesis describes the predicted relationship among the stre ssor, exposure, and assessment endpoint response along with the rationale for their selection. For prohexadione calcium, the following ecological risk hypothesis is being emplo yed 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 actio n 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 acc ordance 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 prohexadio ne 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 Exposu re 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**

**Att ribute**  **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 We t/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** 

**At tribute**  **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

We t/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 Ha ve a Low Likelihood of Contributing to**  **Ecological Risk. 7. Analysis Plan**  In order to address the risk hy pothesis, 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 Concer n**  The major transformation product of prohexadione calcium is despropionyl, which degrades further into tricarball yl ic acid and citric acid. Both tricarball yl ic acid and citric acid are naturall y occurring substances. Currentl y, there are no known toxicol ogical concerns associated with **Stressor Source** 

**Attribute Change**  Prohexadio ne 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

### 16

prohexadione calcium transformation products. Therefore, onl y 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 o ne 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 (US EPA , 2004; USFWS/NMFS , 2004). **7.2. Measures of Exposure** In order to estimate risks of prohexadi one 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 websit e: 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, av ailable monitoring data will be evaluated. Monitoring data will include those collected/reported b y 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 bird s 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. I f STIR predicts that exposure is likely, additional inhalation data may be necessary

to adequatel y 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 L C 50 

### > 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 Off

ice of Research and Development and the National Health and Environmental Effects Research Laboratory's Mid - Continent Ecology Division (USEPA, 2009 a ). 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 directl y 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

Panels 6 

### and have been deemed as appropriate means of refining assessments where deterministic approaches have identified risk s. **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 prohexadio ne 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 b y FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outco mes 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 los s, 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 o f 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 subje ct 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 b y a “naturally occurring estrogen, or other such endocrine effects as th e 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 ho rmonal 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 subs tance, 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 assay s 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 p rohexadione 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 use d 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 concentration s found in ground water used as drinking water. Alternativel y, 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 bel ow, which are not recommended for request at this time). N o 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 purpos es, it would be helpful for these studies to be formall y 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 Hydroly sis 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 wa s submitted for registration in the EU. For harmonization purposes, it wo uld be helpful for this study to be formally sub mitted 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 wa s submitted for registration in the EU. For harmonization purposes, it wo uld 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 metabolite s 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 --

### 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 wa s submitted for registration in the EU. For harmonization purposes, it wo uld 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. 1993/107 67. 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 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 --

### 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 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. D ata gaps are included in **Tables 7.2** to **7.4** , below. **Table 7.2. Available Ecological Effects Data for Terrestrial A nim**  **als Exposed t o Prohexadione**  **C alcium and Remaining Data Gaps**  **Guideline Description**  **MRID Classification**  **Data Gap According**  **to 40 CFR Part 158**  **? Additional Data Recommended** 

**for Request? (Risk Managem**  **ent 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 A nim**  **als Exposed t o Prohexadione**  **C alcium and Remaining Data Gaps**  **Guideline Description**  **MRID Classification**  **Data Gap According**  **to 40 CFR Part 158**  **? Additional Data Recommended** 

**for Request? (Risk Managem**  **ent Recommendations)** 

444577 - 28 Supplemental **Yes No**  . Low overall hatching success wa s 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. The re 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 A nimals Exposed to**  **Prohexadione C alcium and Remaining Data Gaps**  **Guideline Description**  **MRID Classification**  **Data Gap According**  **to 40 CFR Part 158**  **? Additional Data** 

**Recommended for Request? (Risk Managem**  **ent Recomm**  **endations)**

850.1075 Freshwater fish

–

Ac ute 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 A**  **nimals Exposed to Prohexadione C**  **alcium and Remaining Data Gaps Guideline**  **Description MRID**  **Classification Data Gap**  **According to 40 CFR**  **Part 158 ?**  **Additional Data**

**Recommended for Request? (Risk Managem**  **ent Recomm**  **endations)**

444577 - 29 Warmwater Supplemental bluegill sunfish rather than the required 100 mg a.i./L. However, no fish died in either st udy and no sublethal effects were observed. Therefore, it is not likely that a definitive LC 50 wo uld be obtained by repeating the study at a slightly increased concentration. 850.1075 Estuarine/marine fish

–

Ac ute toxicity 444577 - 32 Acceptable No -- 850.1010 Freshwater

invertebrates

– Ac ute toxicity 444577 - 31 Acceptable No -- 850.1025 850.1035 Estuarine/marine

invertebrates

– Ac ute 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 a cceptable 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 compari son 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**  . Grow th measurements were not reported. Therefore, the study endpoints are based on reproduction only (no significant mo rtality was observed).

### 26

**Table 7.3. Available Ecological Effects Data for Aquatic A**  **nimals Exposed to Prohexadione C**  **alcium and Remaining Data Gaps Guideline**  **Description MRID**  **Classification Data Gap**  **According to 40 CFR**  **Part 158 ?**  **Additional Data**

**Recommended for Request? (Risk Managem**  **ent Recomm**  **endations)**

850.1350 Estuarine/marine

invertebrates

– life cycle test Not

submitted Not applicable **Yes No**  . While a cceptable 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 C alcium**  **and Remaining Data Gaps Guideline**  **Description MRID**  **Classification Data Gap**  **According to 40 CFR**  **Part 158 ?**  **Additional Data**

**Recommended for Request? (Risk Managem**  **ent 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 EC 25 s 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, Offic e 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 Pro tection 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. 2012 a . Prohexadione (112600): Screening Level Usage Anal ys is (SLUA). Biological and Economic Anal ys is Division, Office of Pesticide Programs. March 30, 2012 USEPA. 2012 b . Prohe xadione (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 D raft. March 1998.

### 28

**Appendix A. Chemical Structures of P**  **rohexadione C**  **alcium and I ts**  **D egradates**  **Table A -**  **1. Chemical Names and Structures of P**  **rohexadione Calcium and Its**  **D egradates** 

**Chemical Name Structure**  Cyclohexanecarboxylic acid, 3,5 - dioxo 4 - ( 1 - oxopropyl) - , ion (1 - ), calcium, calcium salt ( **Prohexadione calcium**) BASF Code Numbers: BA S 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** 

### C OOO

-O C O H 2 

### C H 3 

### C Ca2+

C O OH O

O C O H 2 

### C H 3 

### C



### C O OH HO

O

C O

OH O

O HO H 3 

### C

C O OH O

O HO HO

### 29

**Table A -**  **1. Chemical Names and Structures of P**  **rohexadione Calcium and Its**  **D egradates** 

**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. Monday, August 06, 2012 Page 1 of 1