              OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
MEMORANDUM	December 6, 2012

Subject:	Registration Review  -  Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Iprodione (PC Code 109801; DP Barcode D402502)

To:		James Parker, Risk Manager Reviewer
		Laura Parsons, Team Leader
		Neil Anderson, Risk Manager
		Risk Management and Implementation Branch 1
		Pesticide Re-evaluation Division

From:		Chuck Peck, Environmental Engineer
		Scott Glaberman, Ph.D., Biologist 
		Environmental Risk Branch IV
		Environmental Fate and Effects Division

Reviewed By: Jim Carleton, Ph.D., Senior Scientist
		Thomas Steeger, Ph.D., Senior Science Advisor
		Environmental Risk Branch IV
		Environmental Fate and Effects Division

Through:	Marietta Echeverria, Branch Chief
		Environmental Risk Branch IV
		Environmental Fate and Effects Division

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation (attached) for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the Registration Review of the fungicide iprodione (PC Code 109801). The problem formulation draws on studies submitted by the technical registrant in response to data requirements, studies available in the open literature, and other supporting documents (e.g., guidance documents, white papers). This document is intended to provide an overview of what is currently known about the environmental fate and ecological effects associated with total toxic residues of iprodione and its degradates, and outlines uncertainties regarding attributes of the parent compound and its transformation products.  It describes the preliminary ecological risk hypothesis and the processes that will be used during the completion of drinking water and ecological risk assessments in support of Registration Review.  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 iprodione.
			
                                       
				
                          Problem Formulation for the
Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments in Support of the Registration Review of Iprodione

                                       

3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidinecarboxa-mide
                              CAS No. 36734-19-7
                                PC Code: 109801
                                       
Prepared by:
Chuck Peck, Environmental Engineer
Scott Glaberman, Ph.D., Biologist
U. S. Environmental Protection Agency
Office of Pesticide Programs
Environmental Fate and Effects Division
Environmental Risk Branch IV
1200 Pennsylvania Ave., NW
Mail Code 7507P
Washington, DC 20460
Reviewed by:
Jim Carleton, Ph.D., Senior Scientist
Thomas Steeger, Ph.D., Senior Science Advisor
Marietta Echeverria, Branch Chief 




                               December 6, 2012


                                       
Table of Contents
1. Introduction	4
2. Conclusions from Previous Risk Assessments	5
2.1. Ecological Risk Assessments	5
2.2. Drinking Water Exposure Assessments	6
2.3. Clean Water Act Programs	6
3. Environmental Fate and Transport	6
3.1. Parent	6
3.2. Transformation Products of Concern	8
4. Receptors	9
4.1. Effects to Aquatic Organisms	10
4.2. Effects to Terrestrial Organisms	13
4.3. Ecological Incidents	15
5. Exposure Pathways of Concern and Risk Hypothesis	16
6. Analysis Plan	17
6.1. Stressors of Concern	17
6.1.1. Ecological Risk Assessment	17
6.1.2. Drinking Water Assessment	18
6.2. Measures of Exposure	18
6.3. Measures of Effect	18
6.4. Endangered Species Assessments	18
6.5. Endocrine Disruptor Screening Program	19
7. Preliminary Identification of Data Gaps	19
7.1. Environmental Fate Data	19
7.2. Effects Data	22
8. References	30

Appendix A. Chemical Identity Table and Proposed Degradation Pathway	32
Appendix B. BEAD USE and Usage Reports	35
Appendix C. OPPIN Bibliography	38
Appendix D. SIP/STIR Model Results	51
Appendix E. IDS Aggregate Incident Report for Iprodione	53
Appendix F. Data Call-In Justification Tables for Non-guideline / Special Studies	54




Introduction

EFED evaluated the most recent ecological risk and drinking water assessments for iprodione in association with the updated toxicity, exposure, and usage information to determine if sufficient data are available and if further updates are needed to support Registration Review.  Recent risk assessments include a 2012 assessment for the use of iprodione on fruiting vegetables and cucurbits (DP Barcode: D359480+, dated 2/2012).  In addition, EFED considered the latest Agency science policies and risk assessment methodologies.  The structure, chemical name, and other identifiers of iprodione and its major transformation products can be found in the chemical identity table attached to this document (Appendix A).

Iprodione (CAS No. 36734-19-7) is a dicarboximide contact and/or locally systemic fungicide, intended to inhibit germination of fungal spores and the growth of mycelia.    In 2011, the Residues of Concern Knowledge Subcommittee (ROCKS) included three major degradates (e.g., >= 10%) of iprodione as residues of concern, based on structures similar to the parent: 3-(1-methylethyl)-N-(3,5-dichlorophenyl)-2,4-dioxo-1-imidazolidine-carboxamide (RP30228); [(dichloro-3,5-phenyl)-1-isopropylcarbamoyl-3]-2-acetic acid (RP35606); and 3-(3,5-dichlorophenyl)-2,4-dioxo-1-imidazolidine-carboxamide (RP32490) (D393960, October 5, 2011).  Structurally, iprodione is related to dichloroanilines (DCA), with one of its degradates being 3,5-DCA, which is also considered a residue of concern. 

Iprodione is currently registered for use on a variety of field, fruit, and vegetable crops; and on turf (sod farms, golf courses, and ornamental turf uses).  The chemical can be applied by chemigation, aircraft, and foliar ground spray.  Prior assessments have estimated exposure for maximum annual application rates ranging from 0.27 (cotton) to 24 (turf) lbs a.i./A (D359480+, 2/2012).  The chemical profile produced by the Biological and Economic Assessment Division (BEAD), located in the docket, lists the use patterns of maximum exposures for the current uses of iprodione.  A brief summary of this chemical profile is provided in Appendix B.

For risk assessment purposes EFED will employ application scenarios that are expected to result in maximum exposure for each given use.  Absence of information on the labels regarding maximum single application rates, application intervals, allowable annual maximum rates, or application methods will result in conservative assumptions as illustrated in the following examples:

   * If a maximum single application rate is specified with a re-application interval of 7 days without specifying a maximum annual rate, an assumption of 26 applications with 7-day intervals will be used;
   * If a label does not preclude aerial applications, aerial pesticide applications will be assumed;
   * If a label does not specify an application interval, an application interval of 3 days will be assumed.

Conclusions from Previous Risk Assessments

Ecological Risk Assessments

The Agency has conducted ecological risk assessments on iprodione that serve as a basis for this problem formulation, including the 1998 Reregistration Eligibility Decision (RED) (USEPA, 1998), the 2009 California Red-legged Frog (CRLF; Rana draytonii) endangered species assessment (USEPA 2009), and new use assessments in 2007.  The potential risks identified in these assessments are briefly summarized in Table 1 and Table 2 below.

Iprodione has been characterized as moderately mobile, relatively nonvolatile, and most likely to degrade via alkaline hydrolysis (USEPA 2009).

The 1998 RED for iprodione indicated acute and chronic risks to Federally-listed threatened and endangered species (hereafter referred to as "listed") and non-listed terrestrial birds and mammals at the higher application rates (e.g., greater than 4 lbs ai/A/year), particularly for granular products. Risk levels for listed and non-listed freshwater and estuarine/marine invertebrates exceeded levels of concern (LOCs) for acute risk for almost all uses, while chronic risks were only a concern at the highest application rates on turf for freshwater organisms, and on all uses for estuarine/marine organisms.  Freshwater and estuarine/marine vertebrate acute and chronic risk quotient (RQ) values exceeded LOCs only at the highest application rates used on turf.  Nonvascular aquatic plants had LOC exceedences at the highest application rates used on turf and rice.

Iprodione is a member of the imide group of the dicarboximide class of fungicides, as are the active ingredients vinclozolin and procymidone.  In the 2000 RED for vinclozolin (USEPA 2000), the Agency concluded that, while current data were limited, certain evidence was available that these compounds may modulate androgens by a common mechanism of toxicity.  Because of the complexity of the androgen system, a careful evaluation was needed before a formal decision could be made. At that time, the Agency did not believe it had sufficient reliable information concerning common mechanism issues to determine whether or not vinclozolin shares a common mechanism of toxicity with iprodione and/or procymidone. For the purposes of that risk assessment, the Agency assumed that vinclozolin did not share a common mechanism of toxicity with other imide fungicides.

Previous ecological risk assessments (DP Barcode D315437, DP Barcode D313332, USEPA 2007a and DP Barcode D339724, USEPA 2007b) identified acute risks to listed terrestrial birds and mammals, aquatic vertebrates and invertebrates, and aquatic plants. Chronic risks were identified for non-listed terrestrial birds and mammals.  Risks were also identified for listed aquatic plants. At the time terrestrial plant data were unavailable, so acute and chronic risks to terrestrial plants could not be precluded.

The most recent ecological risk assessment was an endangered species assessment conducted for the California Red-legged Frog (USEPA 2009).  Acute and chronic RQs for the aquatic-phase CRLF exceeded the LOCs for all iprodione uses.  Acute and chronic risk LOCs were also exceeded for the majority of the iprodione uses for the terrestrial-phase CRLF.

Previous ecological assessments only focused on risks from iprodione and did not include degradates RP30228, RP35606, and RP32490.  Had exposure values accounted for these residues, RQ values would have been higher and the number of uses/taxa for which acute and/or chronic risk LOCs would have been exceeded likely increased.

Table 1. Potential risk concerns identified in previous assessments for iprodione
                                       
                                     Birds
                                    Mammals
                                  Terrestrial
                                 Invertebrates
                              Aquatic Vertebrates
                             Aquatic Invertebrates
                                  Terrestrial
                                    Plants
                                Aquatic Plants
Non-listed
                                       C
                                       C
                                      --
                                      --
                                      --
                                    No data
                                      --
Listed
                                     A, C
                                     A, C
                                      --
                                     A, C
                                     A, C
                                    No data
                                       A
A- Acute risk, C  -  Chronic risk, -- - no risk

Table 2. Potential environmental concerns identified in previous assessments for iprodione	
                                Bioaccumulation
                           Groundwater Contamination
                                  Persistence
                              Degrades of Concern
                                      √
                                      √
                                Water, Sediment
               3,5-DCA (RP32596), RP30228, RP35606, and RP32490

Drinking Water Exposure Assessments

A drinking water exposure assessment for the proposed new uses of iprodione on fruiting vegetables and cucurbits was conducted in 2012 (USEPA, 2012).  Exposure estimates of iprodione total toxic residues from currently labeled uses that produce maximum exposure (turf) were 92 ug/L (1-in-10-year peak), 31 ug/L (1-in-10-year annual mean), and 18.0 ug/L (30-year mean) for surface water and 0.29 ug/L for ground water.  Exposure estimates of 3,5-DCA from currently labeled uses that produce maximum exposure (turf) were 115 ug/L (1-in-10-year peak), 42 ug/L (1-in-10-year annual mean), and 27.0 ug/L (30-year mean) for surface water and 0.81 ug/L for ground water.  The 2012 drinking water assessment included a comprehensive evaluation of all registered uses and characterized available monitoring data, especially for turf uses, as well as modeling results.  Observed differences in the modeling and monitoring turf concentrations appeared to be driven by the difference in maximum allowable use specified on the labels and the amount that was used during the monitoring study.  

Clean Water Act Programs

Iprodione is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Loads (TMDL) or section 304(a) ambient water quality criteria have been developed for iprodione.  Aquatic life benchmarks have been established for iprodione and are available at http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm.  Any data submitted or otherwise located as part of the Registration Review process may be used to update aquatic life benchmarks if applicable.    

Environmental Fate and Transport

Parent

Iprodione is moderately mobile (FAO soil mobility classification) in soils, with an organic carbon partition coefficient (Koc) around 500 mL/g.  It is not volatile and, as such, is not subject to long-range aerial transport.  Iprodione is expected to be most persistent in acidic environments (pH 5), with hydrolysis half-lives around 130 days in aquatic systems; however, in neutral (pH 7) aquatic systems, the hydrolytic half-life is only 4.7 days, and in alkaline systems (pH 9) iprodione hydrolyzes rapidly (half-life 27 minutes).  As a result, iprodione degradation is expected to occur primarily via hydrolysis in the water in natural aquatic environments.  It should be noted that the half-life in the aerobic aquatic metabolism study is longer (t(1/2) = 9 days at pH 8.5), indicating that the addition of sediment impedes the degradation of iprodione.  As only one aerobic aquatic metabolism study has been submitted, additional data could potentially clarify this uncertainty.  In an aquatic photolysis study, iprodione degraded slowly with a half-life of 67 days in a pH 5 buffered solution, with no major degradates (>=10% of the applied) observed.  The iprodione log octanol/water partition coefficient (log Kow) of 3.1 indicates limited potential for bioaccumulation. According to the submitted study (MRID 430910-01), iprodione does not bioaccumulate appreciably in bluegill sunfish (Lepomis macrochirus), with maximum bioaccumulation factors of only 116X for nonedible tissues, 51X for edible tissues, and 72X for whole fish. Depuration was rapid (t(1/2) < 1 day). 

Submitted iprodione soil degradation studies show high levels of unextracted and unidentified residues, leading to uncertainty in characterization of the chemical's degradation.  In an aerobic soil degradation study (MRID 430910-02), 75-87% of the residues at Day 276 were unextracted and uncharacterized.  Unextracted residues exceeded 10% of applied between Days 14 and 30 of the study.  Thus the extent to which these residues constitute parent iprodione or degradates of concern remains unknown.  However, based on 3,5-DCA's affinity to bind to soil in aged systems or be transformed to other unextracted residues that are not available for off-site transport (see discussion under Section 3.2 Transformation Products of Concern) and that 3,5-DCA is considered the terminal degradate in iprodione metabolism studies, EFED will assume that the unextracted and uncharacterized residues in the iprodione aerobic soil metabolism soil study (MRID 430910-02) are 3,5-DCA.   EFED will conservatively estimate a 75% molar conversion of iprodione to 3,5-DCA.  In terrestrial and aquatic field dissipation studies, iprodione dissipated with half-life (DT50) values ranging from 3 to 7 days, at pH values (6.2-8) which suggest that hydrolytic degradation may have been a contributing factor in the observed dissipation.  However, due to the presence of substantial unextracted/unidentified residues in the aerobic soil metabolism study, the extent to which these DT50 values represent degradation, as opposed to (for example) temporary sequestration of iprodione (and/or its degradates of concern) is not known. 

Table 3 summarizes the general fate properties of iprodione and the three residues of concern RP30228, RP35606, and RP32490.  Table 4 summarizes properties of 3,5-DCA as ascertained using a combination of registrant-submitted studies and the Estimation Program Interface (EPI)Suite of tools.


Table 3. Chemical properties and environmental fate parameters of iprodione
                                   Property
                                     Value
                                  Source/MRID
                                   Comments
Molecular formula
                                 C13H13Cl2N3O3
                                       
                        Formula reported for iprodione
Molecular weight (g/mole)
                                     330.2
                                       
                         Value reported for iprodione
Vapor pressure (Torr, 20[o]C)
                                  1.0x10[-7]
                                   412305-03
                         Value reported for iprodione
Henry's Law Constant 
(atm m[3]/mol)
                                  3.3x10[-9]
                                  calculated
           =(vp/760)/(MW/sol);  vp in Torr; sol in mg/L; MW in g/mol
Octanol/Water Coefficient
(Log Kow, 22°C)
                                      3.1
                                   477788-02
                         Value reported for iprodione
Solubility in water (mg/L, 20[o]C)
                                      13
                                   477788-02
                                       
Hydrolysis half- life (days)
pH
Parent
TTR[1]
                                   418854-01
 Study conducted for 30 days (pH 5), 125 hours (pH 7), and 121 minutes (pH 9).

                                       5
                                       7
                                       9
                                      131
                                      4.7
                                     0.02
                                      772
                                      266
                                      56
                                       
                                       
Aqueous photolysis half- life (days)
                              64 (parent and TTR)
                                   418619-01
                                       
Aerobic soil half-life (days)
                                    Parent
                                      TTR
                                 430910-02[2]
High amounts of unextracted material (75-87%).  These residues are assumed to be 3,5-DCA.

                                      16
                                     19.2
                                       
                                       
Aerobic aquatic half-life (days)
                                    Parent
                                      TTR
                             419276-01/ 425038-01
                                   pH = 8.5

                                       9
                                     60.7
                                       
                                       
Anaerobic aquatic half-life (days)
                                    Parent
                                      TTR
                                   417558-01
                                   pH = 7.4

                                      11
                                      92
                                       
                                       
Organic carbon partitioning coefficient (Koc) (mL/goc)
                                223(sandy loam)
                               432 (loamy sand)
                                  507 (loam)
                                  543 (clay)
                                   433492-02
                         Values reported for iprodione
Bioconcentration factor
                                72 (whole fish)
                                   430910-01
                                       
Terrestrial field dissipation DT50 (days)
                                       
                                    Parent
                                      TTR
                                   418774-01
                                CA - silt loam
                                NC - loamy sand

                                      CA
                                       7
                                      28
                                       


                                      NC
                                     <3
                                     <3
                                       

Aquatic field dissipation DT50
Water
  3.7 days (TX)
  2.9 days (MS)
Sediment
  3.4 months (TX)
  4.1 months (MS)
                                   437183-01
                         Values reported for iprodione
1. TTR = Total Toxic Residue. Includes iprodione, RP30228, RP35606, and RP32490.
2. A second aerobic soil metabolism study (MRID 445905-01) was conducted in 1993. However the study was classified as supplemental because nonextractable [[14]C] residues and volatiles were not measured, so a material balance could not be determined.
   
Transformation Products of Concern

A summary of major degradates observed in laboratory and field studies, their structures, and degradation pathways, as  proposed by the registrant, is provided in Appendix A.  Appendix A also lists the degradates by study type, and the maximum percent of applied at which each of the degradates was detected.  The human Health Effects Division (HED) has identified degradates 3,5-DCA (RP32596), RP30228, RP35606, and RP32490 as residues of concern (D393960, October 5, 2011).  By including the precursor degradates RP30228, RP35606, and RP32490 in the risk assessment with parent iprodione (iprodione TTR) and conducting a separate assessment for 3,5-DCA, the ROCKS felt the overall approach would be sufficiently conservative and protective of the assessed risks, including those for cancer.  As such, this assessment will also separately consider exposures to iprodione TTR and to 3,5-DCA.  

An aerobic soil metabolism study (MRID 452392-01) conducted by applying 3,5-DCA to two different soils showed little evidence that 3,5-DCA appreciably degraded over a 9-month period at 25ºC.  Apparent dissipation was caused by a high level of unextracted residues. Unextracted residues accounted for 66% and 81% of the applied in the two systems.  The only residues that were distinguishable from the applied 3,5-DCA amounted to only 4 to 5% of the applied [14]C.  In order to address the issue of unextracted residues, a second study was submitted in 2010 which used more aggressive analytical methods to extract 3,5-DCA from the soil (MRID 482192-01).  Based on nonlinear regression analysis, estimated half-lives ranged from 40 to 107 days in silt loam and sand soils. Unextractable residues were still high, and averaged 54.4-67.8% of the applied at 119 days posttreatment; however, based on an EPA review of the analytical method, in which sufficiently exhaustive methods were employed to extract 3,5-DCA, it was determined that the 3,5-DCA residues were bound to the soil and assumed unavailable for off-site transport.

Table 4. Summary of fate properties of the iprodione degradate 3,5-DCA
                                   Property
                                     Value
                                  Source/MRID
                                   Comments
Molecular formula
                                   C6H5Cl2N
                                       

Molecular wt
                                      162
                            Product chemistry data

Solubility (mg/L)
                                      784
                                   EPI Suite

Vapor pressure 
(Torr, 25[o]C)
                                  8.5x10[-3]
                                   EPI Suite

Henry's Law Constant
(atm m[3]/mol)
                                    10[-6]
                                   EPI Suite

Aerobic soil half-life (days)
                               50.2 (sandy loam)
                                   430910-02
High levels of unextracted residues (see text). Half-lives do not include unextracted residues based on extensive extraction techniques.

                                7.9 (silt loam)
                               17.6 (sandy loam)
                                   452392-01


                                49 (silt loam)
                                  107 (sand)
                         482192-01 (8.3 mg/kg applied)


                                40 (silt loam)
                                   59 (sand)
                        482192-01 (1.47 mg/kg applied)

Organic carbon partitioning coefficient (Koc) (mL/goc)
                                380 (silt loam)
                               593 (sandy loam)
                               626 (loamy sand)
                           788 (pond sediment, sand)
                                  932 (clay)
                                   451141-01


Receptors

The most sensitive endpoint for each group of organisms will be used in the risk assessment. Assessment endpoints include direct toxic effects on the survival, reproduction, and growth of terrestrial and aquatic life, as well as indirect effects, such as reduction in prey base and/or modification of habitat. A summary of the available aquatic and terrestrial toxicity data for iprodione and its degradates is provided in Sections 4.1 and 4.2, respectively.  In addition, a summary of ecological incidents associated with iprodione is provided in Section 4.3. Further discussion of potential degradate toxicity is provided in the description of the stressors of concern for iprodione (Section 6.1).

Acute toxicity to fish and aquatic invertebrates is categorized using the system shown in Table 5 (USEPA 2004). Acute toxicity to terrestrial fauna (birds and mammals) is categorized using the system shown in Table 6. Acute toxicity categories for plants have not been defined.

Table 5. Categories of acute toxicity for aquatic animals
                                  LC50 (mg/L)
                               Toxicity Category
                                   < 0.1
                               Very highly toxic
                                 > 0.1 - 1
                                 Highly toxic
                                  > 1 - 10
                               Moderately toxic
                                 > 10 - 100
                                Slightly toxic
                                   > 100
                             Practically nontoxic

Table 6. Categories of acute toxicity for terrestrial animals
                                 LD50 (mg/kg)
                                  LC50 (ppm)
                               Toxicity Category
                                    <10
                                    <50
                               Very highly toxic
                                     10-50
                                    50-500
                                 Highly toxic
                                    51-500
                                  501 - 1000
                               Moderately toxic
                                   501-2000
                                  1001 - 5000
                                Slightly toxic
                                   >2000
                                   >5000
                             Practically nontoxic
   
   
Effects to Aquatic Organisms


Table 7 contains a summary of available iprodione toxicity data for aquatic organisms.

Iprodione is highly toxic to freshwater invertebrates and moderately toxic to estuarine/marine invertebrates on an acute exposure basis. No acceptable acute toxicity data are available for freshwater or estuarine/marine fish; since fish serve as surrogates for aquatic-phase amphibians, there is uncertainty regarding the potential effects of iprodione to amphibians as well.  Chronic exposure to iprodione affected survival, growth, and reproduction in freshwater invertebrates and offspring survival in freshwater fish.

Several toxicity studies with aquatic organisms that were submitted to the Agency in the past have recently been re-evaluated and deemed unacceptable due to exposure concentration and/or solubility problems with the test substance (see Table 12 for a list of reclassified studies and the rationale for reclassification).

Acceptable aquatic plant toxicity data for iprodione are available for green algae, marine diatoms, and duckweed (Lemna gibba), but not for freshwater diatoms and cyanobacteria. Green algae and duckweed were not adversely affected by iprodione during limit tests, while a definitive endpoint was derived for marine diatoms.


Table 7.  Aquatic Toxicity Profile for Iprodione 
                                     Group
                                    Species
                                 (Common Name)
                                  Study Type:
                                Measured Effect
                                   Endpoint
                                (Test Duration)
                                 Toxicity Value
                                    mg ai/L
                           (Acute Toxicity Category)
                                     MRID 
                            (Study Classification)
                              Freshwater Fish[1]
                              Pimephales promelas
                               (Fathead Minnow)
                           Chronic early life-stage
                           (Reduced larval survival 
                                     NOAEC
                                   (34 days)
                                     0.26*
                                   405508-01
                                (Supplemental)
                           Freshwater Invertebrates
                                Daphnia  magna
                            Acute (Immobilization)
                                     EC50
                                  (48 hours)
                                     0.24*
                                (Highly Toxic)
                                   416420-01
                                (Supplemental)
                                  Estuarine/
                             Marine Invertebrates
                             Crassostrea virginica
                               (Eastern oyster)
                                     Acute
                              (Shell deposition)
                                     EC50
                                  (96 hours)
                                     2.3*
                              (Moderately Toxic)
                                   404892-02
                                (Supplemental)
                                       
                              Americamysis bahia
                                (Mysid shrimp)
                              Chronic/life-cycle
                                     NOAEC
                                   (28 days)
                                    0.0035*
                                   408322-01
                                       
                                       
                                       
                                     NOAEC
                                   (28 days)
                                <0.015[†]
                                   405508-02
                                (Supplemental)
                            Vascular Aquatic Plants
                                  Lemna gibba
                                  (duckweed)
                     (Frond number, growth rate, biomass)
                                     EC50
                                   (7 days)
                                >12.64[†]
                                   457413-01
                                (Supplemental)
                                       
                                       
                                       
                                     NOAEC
                                     12.64
                                       
                          Non-Vascular Aquatic Plants
                        Pseudokirchneriella subcapitata
                                 (green algae)
                                (Cell density)
                                     EC50
                                 >0.13[†]
                                   416041-07
                              (Supplemental)[‡]
                                       
                                       
                                       
                                     NOAEC
                                     0.13
                                       
                                       
                             Skeletonema costatum
                                (marine diatom)
                                (Cell density)
                                     EC50
                                  (120 hours)
                                    0.226*
                                   416041-09
                                 (Acceptable)
                                       
                                       
                                       
                                     NOAEC
                                  (120 hours)
                                    0.0145*
                                       
EC50 Effect concentration for 50% of the organisms tested; NOAEC no observed adverse effect concentration
* Bold values represent most sensitive endpoint and will be used for RQ calculations unless more sensitive data become available.
[†] Non-definitive study endpoint; cannot be used to calculate RQs for risk estimation.
‡ Freshwater fish may be surrogates for aquatic-phase amphibians.
[§] Study only tested up to 0.13 mg ai/L (0.17 lbs ai/A)

Four degradates of iprodione are considered residues of concern for risk assessment: RP30228, RP35606, RP32490, and 3,5-DCA.  No registrant-sponsored toxicity studies have been submitted for these degradates.  According to the most recent risk assessment of iprodione, several open-literature toxicity studies are available for 3,5-DCA which indicate that this degradate is less toxic to aquatic organisms than iprodione (USEPA, 2009).  However, these open-literature studies have not been thoroughly reviewed by EPA.  A comprehensive literature review of all relevant toxicity studies for 3,5-DCA and other degradates of concern using the ECOTOXicology (ECOTOX) database will be carried out during the upcoming Registration Review ecological risk assessment of iprodione.  Additionally, EPA will consider data for other dichloroanalines and parachloroanalines (e.g., 3,4-DCA, p-chloroaniline) as surrogates in the absence of data for 3,5-DCA.

Effects to Terrestrial Organisms

Table 8 contains a summary of available iprodione toxicity data for terrestrial organisms. Iprodione is classified as practically non-toxic to birds on a subacute dietary exposure basis and practically non-toxic to slightly toxic to birds and mammals on an acute oral exposure basis. Since birds serve as surrogates for reptiles and terrestrial-phase amphibians, and without data to the contrary, toxicity estimates for birds will apply to these other taxa as well. No suitable acute toxicity data are available for young adult honeybees (Apis mellifera), which are used as a surrogate for terrestrial invertebrates; however, it should be noted that a recent incident with honeybees, which reported large losses in bee colonies (approximately 50% of bees), has been attributed to application of iprodione (see Section 4.3 for further description of iprodione-related incidents).

Chronic exposure to iprodione in birds resulted in a NOAEC of 300 mg/kg-diet in the Northern bobwhite quail, with a LOAEC of 1000 mg/kg-diet based on reduced number of eggs laid, decreased hatchling body weight and decreased number of hatchlings per number of eggs set. The most sensitive chronic effects in mammals were during a 2-year feeding carcinogenicity study in rats which reported a NOAEC of 150 ppm (6.1 in males and 8.4 mg/kg/day in females) and a LOAEC of 300 ppm (12.4 in males and 16.5 mg/kg/day in females) based on reduced spermatozoa in the epididymis and reduced secretion of the seminal vesicles of males. The effects of iprodione on sperm and semen production are considered effects that could potentially reduce male fertility and impact reproductive success in mammals. 

No acceptable terrestrial plant toxicity data were identified for iprodione.

Table 8.  Terrestrial toxicity profile for iprodione
                                     Group
                                    Species
                              Study Type (Effect)
                                   Endpoint
                                (Test Duration)
                                Toxicity Value
                           (Acute Toxicity Category)
                                     MRID
                            (Study Classification)
                                  Birds[‡]
                       Anas platyrhynchos (mallard duck)
                             Acute oral (Survival)
                                     LD50
                                (Not Reported)
                         >10,437 mg a.i./kg-bw[†]
                            (Practically non-toxic)
                               Acc. No. 00232703
                                (Supplemental)
                                       
                                       
                         Sub-acute dietary (Survival)
                                     LC50
                                   (8 days)
                        >5,620 mg a.i./kg-diet[†]
                            (Practically non-toxic)
                                   416041-03
                                 (Acceptable)
                                       
                                       
        Reproductive toxicity test (Reduction in 14-day old survivors)
                                     NOAEC
                               300 mg ai/kg-diet
                                        
                                   Acc. No.
                                   00086840
                                 (Acceptable)
                                       
                              Colinus virginianus
                           (Northern Bobwhite Quail)
                             Acute oral (Survival)
                                     LD50
                                   (6 days)
                              930 mg a.i./kg-bw*
                               (Slightly toxic)
                               Acc. No. 00232703
                                (Supplemental)
                                       
                                       
                                       
                                     LD50
                                   (14 days)
                         >2,000 mg a.i./kg-bw[†]
                           (Practically non-toxic) 
                                   416041-01
                                 (Acceptable)
                                       
                                       
                         Sub-acute dietary (Survival)
                                     LC50
                                   (8 days)
                        >5,620 mg a.i./kg-diet[†]
                            (Practically non-toxic)
                                   416041-02
                                 (Acceptable)
                                       
                                       
                             Reproductive toxicity
   (Eggs laid, hatchling body weight, percentage of hatchlings of eggs set)
                                     NOAEC
                              300 mg ai/kg-diet*
                                   Acc. No.
                                   00099126
                                 (Acceptable)
                                    Mammals
                               Rattus norvegicus
                               (laboratory rat)
                             Acute oral (Survival)
                                     LD50
                              1,160 mg ai/kg-bw*
                               (Slightly toxic)
                               Acc. No. 00236497
                                       
                                       
                                       
                                     LD50
                               3,050 mg ai/kg-bw
                            (Practically non-toxic)
                               Acc. No. 00232701
                                       
                                       
                                       
                                     LD50
                               4,468 mg ai/kg-bw
                            (Practically non-toxic)
                                   423063-01
                                       
                                       
                              Rat 2-year feeding/
                             carcinogenicity study
          (Testicular hyperplasia, reduced spermatozoa in epididymis)
                                     NOAEC
                              150 mg ai/kg-diet*
                                   426378-01
                                       
                                       
                  Rat 2-generation reproductive toxicity test
(Decreased parental body weight, body weight gain, and food consumption in both sexes)
                                     NOAEC
                               300 mg ai/kg-diet
                                       
                                   418716-01
                           Terrestrial Invertebrates
                          No Toxicity Data Available
                              Terrestrial Plants
                          No Toxicity Data Available
LC50 lethal concentration for 50% of the animals tested; LD50 lethal dose for 50% of the animals tested; NOAEC no observed adverse effect concentration (mg/kg-diet); NOAEC no observed adverse effect concentration (mg/kg-diet)
* Bold values represent the most sensitive endpoint and will be used for RQ calculations unless more sensitive data become available.
[†] Non-definitive study endpoint; cannot be used to calculate RQs for risk estimation.
‡ Birds represent surrogates for terrestrial-phase amphibians and reptiles.

No iprodione degradate (e.g., RP30228, RP35606, RP32490, and 3,5-DCA) toxicity data are available for terrestrial organisms; however, based on the structural similarity between RP30228, RP35606, RP32490 to iprodione, and in the absence of data to the contrary, the degradates are presumed to exhibit similar toxicity to that of the parent compound .  

As noted in the RED (USEPA 1998), the degradate 3,5-DCA is not a registered pesticide; therefore, there are no FIFRA (Federal Insecticide, Fungicide and Rodenticide Act) toxicology data for this compound. In the past, EPA has used p-chloroaniline (PCA) to assess the carcinogenic risk for other structurally related chloroanilines. The EPA policy specifies that chloroaniline metabolites should be considered to be toxicologically equivalent to PCA unless there is sufficient evidence that the metabolite is not carcinogenic.  Therefore, given the structural similarity of 3,5-DCA and PCA, the degradate is considered to be of concern. For the purposes of risk assessment, if suitable toxicity data are not available for 3,5-DCA, either through registrant-submitted studies or studies located in the ECOTOX database, risks from 3,5-DCA may be evaluated by considering toxicity data from PCA and 3,4-DCA, both of which have similar molecular structures to 3,5-DCA. EFED is also recommending, at a minimum, that a chronic reproduction study with Daphnia be carried out with 3,5-DCA to provide some information on the toxicity of this degradate to aquatic organisms. The results of this study would provide information on the relative toxicity of 3,5-DCA as compared to iprodione, which would help determine whether 3,5-DCA is of toxicological concern for risk assessment. Results from this study would also serve as a basis for comparing the toxicity of 3,5-DCA to PCA and 3,4-DCA, which would indicate whether these chemicals are suitable toxicity surrogates for estimating risks from 3,5-DCA.

 Ecological Incidents

A review of the Ecological Incident Information System (EIIS) for incidents involving iprodione was completed on August 9, 2012. A total of 19 incidents were identified in the EIIS of which fourteen are from iprodione use on blueberries and took place during March/April, 2003 (I014027-001 to I014027-014). Except for one incident in Mississippi, the remainder of the incidents involving blueberries and occurred in Georgia. The damage to blueberries was due to direct treatment with iprodione, but the nature of the damage was not specified in the incident report. The level of certainty that iprodione was the cause of these incidents is listed as "highly probable." All incidents involved registered uses of the substance. 

An incident involving ornamental plants in Washington County, Oregon (IO13636-027), resulted in unspecified damage to 6 acres of tulips following direct application of iprodione on February 4, 2002.

Application of iprodione to an unspecified agricultural area in California (IO20302-002) resulted in the death of honeybee brood following application of Rovral to blooming almond trees. The incident report included an unpublished manuscript by Mussen et al. (2008) describing the adverse effects of the formulated iprodione product Rovral[(R)] on honeybee brood development. The certainty of the bee kill incident being related to iprodione is classified as "probable".

Another bee kill incident was recently reported and took place on March 13, 2012 (I023830-001). Rovral[(R)] fungicide was reportedly applied to a cherry orchard by airblast sprayer during the evening when bees being used for pollination services were in the vicinity. Of the 80 colonies reported to be in the orchard, roughly 20% exhibited a reduction in forage force (reduced numbers of adult bees), and adult bee populations in these colonies were estimated at roughly 50%. Although spraying occurred in the evening hours, bees were likely bearding on the outside of the colonies and were directly sprayed with Rovral[(R)]. This was a registered use of iprodione.

Application of iprodione to golf course turf (B000177-001) in Arlington, Virginia, in 1992 resulted in the death of a single bluebird (Sialia spp.). The legality of the use is not reported and the certainty of it being related to iprodione is classified as "unlikely." This incident is also captured in the Avian Incident Monitoring System (AIMS; American Bird Conservancy 2009) in which it is reported that the insecticide chlorpyrifos (CAS No. 2921-88-2) and the fungicide metalaxyl (57837-19-1) were also in use at the time. Given that chlorpyrifos is considerably more toxic to birds than iprodione on an acute oral and subacute dietary exposure basis, the likelihood that the death of the bluebird resulted from iprodione is considered low.

Only a single aquatic incident is reported in EIIS associated with the registered use of iprodione on golf course turf (I000910-001) in St. John the Baptist Parish, Louisiana, on June 7, 1992. The incident involved the death of an unspecified number of golden shiners (Notemigonus crysoleucas), catfish (Ictaluridae), needlefish (Strongylura exilis), minnows (Cyprinidae), perch (Percidae) and sunfish (Centrarchidae) due to runoff. The certainty of the incident being related to the application of iprodione to the golf course is classified as "possible".

A search of OPP's aggregate incident report database on July 24, 2012 revealed a total of 9 minor plant incidents between 2003 and 2006 that were attributed to iprodione (Appendix E). Since little detail is provided about the individual incidents in the aggregate database, it is unclear whether there is overlap with the plant incident entries in the EIIS database.
	
Exposure Pathways of Concern and Risk Hypothesis

The environmental fate properties of iprodione and its transformation products indicate that direct application, spray drift, and runoff represent potential transport mechanisms of iprodione TTR and 3,5-DCA exposure to aquatic and terrestrial organisms and plants.  Drinking water and inhalation exposure pathways were screened using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods, respectively, and were found to be exposure pathways of low concern (no LOC exceedances are expected) (Appendix D).  SIP and STIR are described in detail at:  http://www.epa.gov/oppefed1/models/terrestrial/index.htm.

Based on previous ecological risk assessments, iprodione has the potential to result in acute risk to listed terrestrial birds and mammals, listed aquatic vertebrates and invertebrates, and aquatic plants, as well as result in chronic risk to listed and non-listed terrestrial birds and mammals and listed aquatic vertebrates and invertebrates.  However, as the prior assessments did not include the new degradates as iprodione residues of concern, the following risk hypothesis will be used for this risk assessment: 

Based on environmental fate parameters and potential transport pathways, iprodione total toxic residues and 3,5-DCA have the potential to reduce survival, reproduction, and/or growth in non-target terrestrial animals, aquatic vertebrates and invertebrates, and aquatic plants 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.

Analysis Plan

Stressors of Concern

Ecological Risk Assessment

The stressors of ecological concern for terrestrial organisms are iprodione and its major degradates RP30228, RP35606, RP32490, and 3,5-DCA (RP32596), the last of which will be assessed separately during risk assessment.  Because of their structural similarity to iprodione and in the absence of data to the contrary, RP30228, RP35606, and RP32490 are expected to have toxicity similar to that of iprodione, and will therefore be included with iprodione as part of total toxic residues (TTR). A TTR approach for the above three degradates is the default option for risk assessment if suitable toxicity information on these degradates is not available. However, if suitable degradate toxicity data are submitted or located through the ECOTOX database, there is the potential to derive exposure and risk values for these degradates independently, or eliminate the degradates from the TTR. Conversely, since the general structural properties of 3,5-DCA are different from iprodione, the mode of action in ecological receptors is also likely to be different. Therefore, 3,5-DCA will be evaluated separately during risk assessment using a separate set of exposure and toxicity values. A list and discussion of recommended toxicity data for iprodione degradates is provided in Section 7.2 and Table 13.

In an effort to generate at least some relative toxicity information for iprodione and its degradates for purposes of problem formulation, toxicity estimates were obtained using the Assessment Tools for the Evaluation of Risk (ASTER) (Table 9).  The ASTER database integrates aquatic and terrestrial toxicity information and quantitative structure activity relationships (QSARs) to assess the environmental toxicity of discrete chemicals. ASTER is designed to provide high quality data for discrete chemicals, when available in the ECOTOX database, and mechanistically-based QSAR estimates when data are lacking. Based on a comparison of QSAR-predicted toxicity values for parent and degradates, RP30228 and RP35606 are potentially more toxic than the parent based on QSAR estimates, while degradate RP32490 appears to be substantially less toxic than the parent. The degradate 3,5-DCA is also potentially more toxic than iprodione, but will be assessed separately.  It should be noted that the mode of action basis from QSAR predictions in ASTER was nonpolar narcosis for iprodione and its structurally similar degradates, and polar narcosis for 3,5-DCA. Since these modes of action are highly non-specific, they are of limited utility for predicting toxicity.

Table 9. ASTER Ecotoxicity Profile for Iprodione and Degradates.
                                   Compound
               Estimated 4-day LC50 Median Concentration (ug/L)
                                       
                             Pimephales promelas 
                               (fathead minnow)
                              Ictalurus punctatus
                               (channel catfish)
                                 Daphnia magna
                                  (waterflea)
                              Oncorhynchus mykiss
                                (rainbow trout)
                              Lepomis macrochirus
                              (bluegill sunfish)
                                   Iprodione
                                    23,310
                                    10,062
                                    13,251
                                     9,473
                                    18,645
                              3,5-Dichloraniline
                                   (RP32596)
                                    14,198
                                     6,127
                                     7,983
                                     5,820
                                    11,307
                                    RP30228
                                    16,019
                                     6,918
                                     9,282
                                     6,413
                                    12,910
                                    RP32490
                                    505,614
                                    217,558
                                    243,983
                                    233,664
                                    379,257
                                    RP35606
                                     5,349
                                     2,312
                                     3,287
                                     2,045
                                     4,411
Note: all toxicity estimates in this table are based on QSAR, as ASTER did not identify any empirical toxicity data for degradates through the ECOTOX database.
 
Drinking Water Assessment

In 2012 a drinking water assessment (USEPA 2012, D359480+) was conducted which modeled separately the estimated drinking water concentrations (EDWCs) for iprodione residues of concern (iprodione and the three degradates RP30228, RP35606, and RP 32490) and 3,5-DCA in surface water and groundwater. The 3,5-DCA was assessed separately because the mechanism of action for 3,5-DCA is different from that of iprodione.  Pending receipt and review of additional environmental fate and toxicity data for iprodione and its degradates, or changes in labeled use rates, the drinking water assessment will be reevaluated.  However, if no new, relevant data regarding the environmental fate, toxicity, or use of iprodione or its degradates are submitted, the EDWCs from the 2012 drinking water assessment will be used in this risk assessment.

Measures of Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm.

Iprodione residues of concern (iprodione and the three degradates RP30228, RP35606, and RP 32490) and 3,5-DCA will be modeled separately in aquatic environments.

Measures of Effect

Selected toxicity data presented in Section 4 of this problem formulation will be used to calculate RQ values.  Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will also be considered.  The open literature studies are identified using EPA's ECOTOX database, which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife.  The evaluation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communities.

Endangered Species Assessments

Consistent with the Agency's responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to listed species from registered uses of pesticides in Registration Review.  These assessments will be conducted in accordance with standard EPA procedures and good scientific judgment. The process for evaluating potential risks to listed species is further described in the Overview Document at http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm.
 
Endocrine Disruptor Screening Program

As required by FIFRA and the Federal Food Drug and Cosmetic Act (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 reregistration 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), iprodione 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.  Iprodione was included on that list and an order has been issued to conduct the Tier 1 testing.  Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if necessary.  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/.

Preliminary Identification of Data Gaps 

Environmental Fate Data

Table 10 identifies environmental fate studies by MRID that provide data on iprodione for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment.  Studies identified as needed in Table 10 should be conducted using the parent; however, the formation and decline of the degradates, particularly RP30228, RP35606, RP32490 and 3,5-DCA, should also be monitored to determine if degradate-specific half-life values can be estimated.  It should be noted that separate environmental fate studies have not been submitted for the iprodione degradates RP30228, RP35606, and RP32490.  As EFED will be evaluating risk to these degradates using a TTR approach, a batch equilibrium study (OCSPP (formerly OPPTS) Guideline 835. 1230) should be conducted for each of the three degradates to determine if they are more mobile than the parent.  If toxicity data are provided indicating that one or all of the degradates are less toxic than the parent, they may be removed from the risk analysis.  

Table 11 provides the same data for the iprodione degradate 3,5-DCA.    Because this transformation product has a different mechanism of action than that of iprodione, the following kinds of fate studies stipulated under 40 CFR 158 data requirements would help clarify the overall risk picture for 3,5- DCA: OCSPP Guidelines 835.2120 (hydrolysis), 835.2240 (aqueous photolysis), 835.2410 (soil photolysis), 835.4300 (aerobic aquatic metabolism), and 835.4400 (anaerobic aquatic metabolism).  In the absence of such data EFED will consider this degradate stable to these transformation pathways. 

Table 10. Submitted environmental fate data for iprodione
                                OCSPP Guideline
                               Data Requirement
                     Submitted Studies (Acc. No. or MRID)
                             Study Classifications
                  Are data needed to conduct risk assessment?
        Justification and Assumptions EPA will Make in Absence of Data
835.2120
Hydrolysis
                                   418854-01
                                  Acceptable
                                      No



                                   00059481
                                  Acceptable
                                       



                                   00068287
                                 Unacceptable
                                       

835.2240
Aqueous photolysis
                                  418619-01/
                                   422013-01
                                  Acceptable
                                      No

835.2410
Soil photolysis
                                   419121-01
                                 Unacceptable
                                      No



                                   428971-01
                                  Acceptable
                                       

835.4100
Aerobic soil metabolism
                                   430910-02
                                  Acceptable
                                      Yes
Data are required for four soils. MRID 43091002 was acceptable for one soil, so a study with three additional soils is required. MRID 44590501 cannot be used for half-life estimates as material balance could not be determined.  In lieu of data, EFED will assume a TTR half-life value of 58 days (3x singlevalue).


                                   445905-01
                                 Supplemental


835.4200
Anaerobic soil metabolism
                                      --
                                      --
                                      No
No data submitted.  Data not necessary for modeling purposes. Will use information from anaerobic aquatic metabolism for characterization purposes.
835.4300
Aerobic aquatic metabolism
                                   00162219
                                 Unacceptable
                                      Yes
Data are required for two water/sediments systems.  Currently only have one system, so an additional study is required.  In lieu of additional data, EFED will assume a TTR half-life value of 183 days (3 x 61 days).


                                  419276-01/
                                   425038-01
                                  Acceptable
                                       



                                   416002-01
                                 Unacceptable
                                       
                                       


                                   446050-01
                                 Unacceptable
                                       
                                       
835.4400
Anaerobic aquatic metabolism
                                   00162220
                                 Unacceptable
                                      Yes
Data are required for two water/sediments systems.  Currently only have one system, so an additional study is required. In lieu of additional data, EFED will assume a TTR half-life value of 276 days (3 x 92 days).


                                  417558-01/
                                   428541-01
                                  Acceptable
                                       

835.1230
Adsorption/ desorption 
                                   00059479
                                  Acceptable
                                      Yes
Batch equilibrium studies are required for the three degradates RP30228, RP35606, and RP32490.


                                   00068286
                                  Acceptable
                                       



                                   418788-01
                                 Unacceptable
                                       



                                   433492-02
                                  Acceptable
                                       

835.1240
Leaching
                                   418896-01
                                 Unacceptable
                                      No



                                   433492-01
                                  Acceptable
                                       

835.6100
Terrestrial field dissipation
                                   00059484
                                   Acceptable
                                      No
 Study conducted with 8 applications at 1 lb ai/A. Other uses have higher single application rates.


                                   00068290
                                   Acceptable
                                       
 


                                   418774-01
                                   Acceptable
                                       
 

Analytical method in soil
                                   437183-02
                                  Acceptable
                                       
                                       
835.6200
Aquatic field dissipation
                                   00162218
                                 Unacceptable
                                      No
 


                                   437183-01
                                  Acceptable
                                       
                                        

Analytical method in water
                                   452392-03
                                  Acceptable
                                       
                                       
165-4 (850.1730)
Fish bioconcentration
                                   00162221
                                 Supplemental
                                      No



                                   00162222
                                 Supplemental
                                       
                                       


                                   430910-01
                                  Acceptable
                                       
                                       

Table 11. Submitted environmental fate data for the iprodione transformation product 3,5-DCA
                                OCSPP Guideline
                               Data Requirement
                           Submitted Studies (MRID)
                             Study Classifications
                  Are data needed to conduct risk assessment?
        Justification and Assumptions EPA will Make in Absence of Data
835.2120
Hydrolysis
                                      --
                                      --
                                      Yes
No data submitted. In lieu of data, EFED will assume 3,5-DCA is stable to hydrolysis.
835.2240
Aqueous photolysis
                                      --
                                      --
                                      Yes
No data submitted. In lieu of data, EFED will assume 3,5-DCA is stable to aqueous photolysis.
835.2410
Soil photolysis
                                      --
                                      --
                                      Yes
No data submitted. In lieu of data, EFED will assume 3,5-DCA is stable to soil photolysis.
835.4100
Aerobic soil metabolism
                                   430910-02
                                  Acceptable
                                      No



                                   452392-01
                                  Acceptable
                                       



                                   482192-01
                                  Acceptable
                                       

835.4300
Aerobic aquatic metabolism
                                      --
                                      --
                                      Yes
No data submitted.  In lieu of data, EFED will assume a half-life of 129 days (2 x the 90% upper confidence limit around the mean value for the aerobic soil half-life).
835.4400
Anaerobic aquatic metabolism
                                      --
                                      --
                                      Yes
No data submitted.  In lieu of data, EFED will assume 3,5-DCA is stable to anaerobic aquatic metabolism.
835.1230
Adsorption/ desorption
                                   451141-01
                                  Acceptable
                                      No


Effects Data

Table 12 identifies all available ecological effects studies for iprodione by MRID or Accession Number (Acc. No.), as well as a description of whether further data are needed to support risk assessment.

In addition, the following rationale is being used to justify asking for particular non-guideline studies. 

   * Honeybee Larval Toxicity Study w/ TGAI  -  Non-guideline [1 Study]                                                                                                                                                                                                                                                                                                                                                                                

Incident data (IO20302-002; Mussen et al. 2008) suggest that iprodione may adversely affect honeybee brood (larval and pupal bees) development. In addition, iprodione has been reported to occur in bee colony wax samples, where it could potentially affect development of young (vanEnglesdorp et al., 2009). Therefore, a non-guideline honeybee larval toxicity study is recommended. Honeybee brood studies are not currently a data requirement in the U.S., however, a non-guideline honeybee larval toxicity study is recommended as a special study (see Appendix F for DCI justification table).  Since this is a non-guideline study, EFED recommends that the proposed study protocol be submitted for review and approval prior to study initiation. The following references may be useful in the design of a larval toxicity test: (1) Aupinel P, Fortini D, Michaud B, Marolleau F, Tasei JN, Odoux JF. 2007. Toxicity of dimethoate and fenoxycarb to honey bee brood (Apis mellifera), using a new in vitro standardized feeding method. Pest Management Science 63:1090-1094; (2) Oomen PA, De Ruijter A, Van Der Steen J. 1992Method for honeybee brood feeding tests with insect growth-regulating insecticides. EPPO Bulletin 22:613-616.

   * Honeybee Acute Oral Toxicity Study w/ TGAI  -  OECD TG213 [1 Study]                                                                                                                                                                                                                                                                                                                                                                                

Iprodione is applied to several pollinated crops, including almonds, which had the highest annual usage of iprodione from 2003-2010 (Apppendix B). Therefore, exposure to foraging worker bees is possible. EFED is also recommending toxicity data for honeybees on an acute oral exposure basis to account for potential differences in sensitivity when exposed via contact versus oral routes.

Table 12.  Submitted terrestrial and aquatic animal ecological effects data for iprodione (parent)
                                   Guideline
                         Description -- Test Substance
                                     MRID
                             Study Classification
                     Are data Needed for Risk Assessment?
        Justification and Assumptions EPA will Make in Absence of Data
Avian and Mammalian Testing
                                   850.2100
                  Avian acute oral toxicity, waterfowl -- TGAI
                               Acc. No. 00232703
                                 Supplemental
                                      No
              Number of study animals per test level not reported
                                       
          Avian acute oral toxicity, upland game bird species -- TGAI
                               Acc. No. 00232703
                                 Supplemental
                                      No
Study recently reclassified from acceptable to supplemental due to lack of reported information about sublethal effects and test conditions
                                       
                                       
                                   416041-01
                                  Acceptable
                                      No
                                       
                                       
              Avian acute oral toxicity, passerine species -- TGAI
                                     None
                                      N/A
                                      Yes
Part of  40 CFR Part 158 data requirements as of December 2007 to address passerine sensitivity. 
                                       
In addition, a passerine study could help resolve uncertainty surrounding toxicity of iprodione to birds, since two acute oral toxicity studies in bobwhite quail yielded conflicting results. Study Acc. No. 00232703 resulted in LD50 of 930 mg ai/kg-bw, while study MRID 416041-01 resulted in LD50 of >2,000 mg ai/kg-bw.
                                   850.2200
               Avian dietary toxicity, waterfowl species -- TGAI
                                   416041-03
                                  Acceptable
                                      No
Non-definitive endpoint of 5,620 mg a.i./kg-diet is <10  times the dietary EEC for all food items except fruits, pods, and seeds at current maximum application rate (turf) of 24 lbs ai/A
                                       
                Avian dietary toxicity, upland game bird -- TGAI
                                   416041-02
                                  Acceptable
                                      No
Non-definitive endpoint of 5,620 mg a.i./kg-diet is <10  times the dietary EEC for all food items except fruits, pods, and seeds at current maximum application rate (turf) of 24 lbs ai/A
                                   850.2300
                 Avian reproduction, waterfowl species -- TGAI
                                   Acc. No.
                                   00086840
                                  Acceptable
                                      No
                                       
                                   850.2300
              Avian reproduction, upland game bird species -- TGAI
                                   Acc. No.
                                   00099126
                                  Acceptable
                                      No
                                       
                                   850.2400
                          Wild mammal toxicity -- TGAI
                                     None
                                      N/A
                                      No
Not triggered based on ecotoxicity data, predicted EECs, fate properties, and use pattern criteria.
                                   850.2500
                    Simulated or actual field testing -- TEP
                                     None
                                      N/A
                                      No
Not triggered based on ecotoxicity data, predicted EECs, fate properties, and use pattern criteria.
                            Aquatic Animal Testing
                                   850.1010
                Freshwater invertebrate, acute toxicity -- TGAI
                                   416420-01
                                 Supplemental
                                      No
         Study recently reclassified from unacceptable to supplemental
                                       
                 Freshwater invertebrate, acute toxicity -- TEP
                                     None
                                      N/A
                                      Yes
Study required when product(s) are applied directly to water, as in the case of the iprodione rice use. A study should be performed on one representative end use product used on rice (e.g., EPA Reg. No. 264-689, 66222-144, 264-482, 264-524, 264-532)
                                   850.1025
                Estuarine/Marine Mollusk acute toxicity -- TGAI
                                   404892-02
                                 Supplemental
                                      No
                                       
                                   850.1035
               Estuarine/Marine crustacean acute toxicity -- TGAI
                                   404892-04
                                 Unacceptable
                                      Yes
Precipitate observed during test and filtration was not reported. Estuarine/marine invertebrate acute toxicity data is a standard data requirement in Part of 40 CFR Part 158. In addition, a new study is also recommended because iprodione can be applied directly to water for use on rice.
                                   850.1075
                    Freshwater fish, acute toxicity -- TGAI
                                   Acc. No.
                                   00162224
                                 Unacceptable
                                      No
Study recently reclassified from supplemental to unacceptable; precipitate was observed during test and filtration was not reported
                                       
          Freshwater fish, acute toxicity, warm water species -- TGAI
                                   416041-04
                                 Unacceptable
                                      Yes
Precipitate observed at all test concentrations and filtration was not reported
                                       
          Freshwater fish, acute toxicity, cold water species -- TGAI
                                   416041-05
                                 Unacceptable
                                      Yes
   Test substance concentrations not consistent between sampling time points
                                       
   Freshwater fish, acute toxicity, warm water species -- TEP (Rovral 50 WP)
                                   404892-03
                                 Unacceptable
                                      No
Study recently reclassified from supplemental to unacceptable; precipitate was observed at all test concentrations and filtration was not reported
                                       
                  Estuarine/Marine fish acute toxicity -- TGAI
                                   404892-05
                                 Unacceptable
                                      Yes
Study recently reclassified from supplemental to unacceptable; precipitate observed during test and filtration was not reported
                                   850.1300
                           Freshwater invertebrate,
                           reproduction test -- TGAI
                                   404892-01
                                 Unacceptable
                                      Yes
The test concentrations varied substantially throughout the test period (i.e., the highest measured concentration in three treatments was more than twice the lowest in the same concentration).
                                   850.1350
                        Estuarine/marine invertebrate,
                           reproduction test -- TGAI
                                  408322-01/
                                   405508-02
                                 Supplemental
                                      Yes
Reproductive effects occurred at all test levels, indicating need for additional testing. Test is triggered according to 40 CFR §158.630 15(ii): test is required if acute LC50 or EC50 <1 mg/l.
                                   850.1400
                 Freshwater fish, early life stage test -- TGAI
                                   405508-01
                                 Supplemental
                                      No
Study recently reclassified from acceptable to supplemental due to lack of information provided in study report
                                       
                 Saltwater fish, early life stage test -- TGAI
                                     None
                                      N/A
                                      Yes
Need for this test cannot be determined until an acceptable acute toxicity study (850.1075) with an estuarine/marine fish species is submitted. If a saltwater fish ELS study is not submitted, an acute-to-chronic ratio using freshwater fish acute and chronic data and saltwater fish acute data will be used to derive a saltwater fish chronic endpoint during risk assessment.
                                   850.1500
                        Freshwater fish life cycle test
                                     None
                                      N/A
                                      Yes
Aquatic EECs are > 0.1 of the estuarine/marine invertebrate life cycle test NOAEC of 0.0035 mg a.i./L; EECs are > 0.1 of the NOAECs from the freshwater fish ELS study (NOAEC=0.26 mg a.i./L) and the daphnid life cycle study (NOAEC=0.26 mg a.i./L) for ornamental uses of iprodione.  An additional rationale for recommending this study includes the potential anti-androgenic effects of iprodione as well as the potential exposure to aquatic organisms through direct application of iprodione to water during use on rice.
                                       
                     Estuarine/marine fish life cycle test
                                     None
                                      N/A
                                      No
                                       
                                   850.1950
            Simulated or actual field testing for aquatic organisms
                                     None
                                      N/A
                                      No
Higher tier testing to address risk uncertainties have not been identified at this time
                               Sediment Testing
850.1735
              Whole sediment 10-d freshwater invertebrate -- TGAI
                                     None
                                      N/A
                                      No
Data requirement not triggered since Kd <50 and Koc <1,000.  Although log Kow of 3.1 is slightly greater than trigger value (KOW >3), the short hydrolysis half lives (5-9 days) indicate that the compound is not expected to persist in aquatic environments.
850.1740
           Whole sediment 10-d estuarine/marine invertebrate -- TGAI
                                     None
                                      N/A
                                      No
Data requirement not triggered since Kd <50 and Koc <1,000.  Although log Kow of 3.1 is slightly greater than trigger value (Kow >3), the short hydrolysis half lives (5-9 days) indicate that the compound is not expected to persist in aquatic environments.
Agency-wide guideline
      Whole sediment chronic freshwater and/or marine invertebrate -- TGAI
                                     None
                                      N/A
                                      No
Data requirement not triggered since Kd <50 and Koc <1,000.  Although log Kow of 3.1 is slightly greater than trigger value (Kow >3), the short hydrolysis half lives (5-9 days) indicate that the compound is not expected to persist in aquatic environments.
                           Insect Pollinator Testing
850.3020
                    Honeybee acute contact toxicity -- TGAI
                                   442620-01
                                 Supplemental
                                      No
An acute contact toxicity study is available for honeybees that originated in the open-literature (MRID 44262001); this study provides insufficient information on methods and results to make it useful for risk assessment; however, an acute oral study is being requested in lieu of an additional acute contact study. 
OECD 213
                  Honeybee acute oral toxicity study -- TGAI 
                                     None
                                      N/A
                                      Yes
                       Study guideline can be found at:
http://www.oecd-ilibrary.org/docserver/download/fulltext/9721301e.pdf?expires=1345126780&id=id&accname=freeContent&checksum=3D3E8D93D5EB11D6F751673FFFC8725F
850.3030
                Honeybee toxicity of residues on foliage -- TEP
                                     None
                                      N/A
                                      No
                        Data requirement not triggered
Non-guideline
                          Larval Toxicity Test -- TGAI
                                     None
                                      N/A
                                      Yes
Recommended based on incident data from larval bees as well as detection of iprodione in bee hives where larvae may be exposed.
                                       
  It is recommended that a protocol be submitted before conducting this test.
850.3040
                         Field testing for pollinators
                                     None
                                      N/A
                                      No
Field testing to address risk uncertainties have not been identified at this time
                           Terrestrial Plant Testing
                                   850.4100
                               Tier I and/or II
                     Seedling emergence (10 species) -- TEP
                                     None
                                      N/A
                                      Yes
Submitted study should test up to highest currently registered application rate of iprodione.
                                   850.4150
                               Tier I and/or II
                      Vegetative vigor (10 species) -- TEP
                                     None
                                      N/A
                                      Yes
Submitted study should test up to highest currently registered application rate of iprodione.
                             Aquatic Plant Testing
                                   850.4400
                               Tier I and/or II
             Tier II Aquatic plant growth, vascular plant  --  TGAI
                                   457413-01
                                 Supplemental
                                      No
Test evaluates up to 12.64 mg a.i./L (i.e., 16.8 lbs a.i./A). However, maximum iprodione application rate is 24 lbs a.i./A, and aquatic EECs range from 0.014 to 51 mg a.i./L for various registered uses of iprodione. However, solubility limit of iprodione is 13 mg/L.
                                   850.4500*
                               Tier I and/or II
         Tier II Aquatic Plant, freshwater green alga species -- TGAI 
                                   416041-07
                                  Acceptable
                                      Yes
Test evaluates up to 0.13 mg a.i./L (i.e., 0.17 lbs a.i./A). However, maximum iprodione application rate is 24 lbs a.i./A for turf use. In addition, aquatic EECs range from 0.014 to 51 mg a.i./L for various registered uses of iprodione. Therefore additional testing at higher concentrations is needed.
                                   850.4500*
                               Tier I and/or II
               Tier II Aquatic Plant, freshwater diatom -- TGAI 
                                   416041-11
                                 Unacceptable
                                      Yes
     Study deemed unacceptable due to cell adhesion to flasks during test.
                                       
Note: new study should test up to highest application rate and/or aquatic EECs as defined in this problem formulation or previous risk assessments.
                                   850.4500*
                               Tier I and/or II
                 Tier I Aquatic Plant, marine diatom  --  TGAI
                                   416041-09
                                  Acceptable
                                      No
<50% reduction in growth observed a limit dose. Also, the maximum peak EEC is more than 10 times lower than the limit concentration tested. Tier II testing is not recommended.
                                 850.4550[†]
                             Tier I and/or Tier II
                Tier II Aquatic Plant, cyanobacterium  --  TGAI 
                                   416041-10
                                 Unacceptable
                                      Yes
       Study deemed unacceptable due to erratic cell counts during test.
                                       
Note: new study should test up to highest application rate and/or aquatic EECs as defined in this problem formulation or previous risk assessments.
TGAI = Technical Grade Active Ingredient
TEP = technical end product
* Algal toxicity tests are now under guideline OCSPP 850.4500 (formerly 850.5400)
[†] Cyanobacterium tests are now under guideline 850.4550 (formerly 850.5400)

For the major degradates RP30228, RP35606, and RP32490, no toxicity data are available for any animal or plant taxa.  Therefore, there are insufficient data to evaluate these degradates in the Registration Review risk assessment for iprodione.  In the absence of any new toxicity data for these degradates, a TTR approach will be used in which total residue data for iprodione, RP30228, RP35606, and RP32490 will be compared to available toxicity data for the parent compound. A TTR approach is appropriate for these three degradates since they have very similar molecular structures as the parent and would likely result in similar levels of toxicity.

No ecological effects data have been submitted for 3,5-DCA (RP32596), which is another degradate of concern for iprodione. Since 3,5-DCA likely has a different mode of action in ecological receptors as compared to iprodione, including this degradate in the TTR approach is not appropriate. Therefore, during the risk assessment, if suitable toxicity data are not available for 3,5-DCA, either through registrant-submitted studies or studies located in the ECOTOX database, risks from 3,5-DCA may be evaluated by considering toxicity data from PCA and 3,4-DCA, both of which have similar molecular structures to 3,5-DCA. EFED is recommending, at a minimum, that a chronic reproduction study with Daphnia be carried out with 3,5-DCA to provide some information on the toxicity of this degradate to aquatic organisms. The results of this study would provide information on the relative toxicity of 3,5-DCA to iprodione, which would help determine whether 3,5-DCA is of toxicological concern for risk assessment. Results from this study would also serve as a basis for comparing the toxicity of 3,5-DCA to PCA and 3,4-DCA, which would indicate whether these chemicals are suitable toxicity surrogates for estimating risks from 3,5-DCA (see Appendix F for DCI justification table).

Table 13. Ecological effects data for iprodione transformation products
                                   Guideline
                                  Description
                                     MRID
                             Study Classification
                     Are data Needed for Risk Assessment?
                                   Comments
                                   850.1300
                           Freshwater invertebrate,
                     reproduction test -- RP32596 (3,5-DCA)
                                     None
                                      N/A
                                      Yes
In the absence of this or other submitted data, risks to aquatic organisms will based on ECOTOX open-literature studies or toxicity endpoints for 4-chloroaniline and 3,4-dichloroaniline, which have similar structures to 3,5-DCA

References

Mussen EC, Lopez JE, Peng CYS. Effects of Selected Fungicides on Growth and Development of Larval Honey Bees, Apis mellifera L. (Hymenoptera: Apidae). Environmental Entymology 33(5):1151-1154. 

United States Environmental Protection Agency (USEPA). 1998. Registration Eligibility Decision (RED) Iprodione. USEPA, Prevention, Pesticides, and Toxic Substances. EPA-738-R-98-019. November 1998

USEPA. 2000. Registration Eligibility Decision (RED) Vinclozalin. USEPA, Prevention, Pesticides, and Toxic Substances. EPA-738-R-00-023. October 2000

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection Agency. January 23, 2004

USEPA. 2007a. Memorandum: Review of Iprodione (PC Code 109801) Revised Application Rates and New IR-4 Use. Environmental Fate and Effects Division. March 31, 2007. DP Barcodes: D315437 and D313332

USEPA. 2007b. Memorandum: Section 18 Emergency Exemption Request for Use of Iprodione (PC Code 109801) on Almonds in California. Environmental Fate and Effects Division. May 10, 2007. DP Barcodes: D339724

USEPA. 2009. Risks of Iprodione Use to Federally Threatened California Red-legged Frog
(Rana aurora draytonii). Pesticide Effects Determination. Environmental Fate and Effects Division. October 16, 2009

USEPA. 2011. Memorandum: Iprodione; Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS). Health Effects Division. October 5, 2011. DP Barcode: D393960.

USEPA. 2012. Memorandum: Refined iprodione drinking water assessment for label amendments and proposed new uses on fruiting vegetables and cucurbits. Environmental Fate and Effects Division. February 28, 2012. DP Barcodes: D359480 and D357471

VanEngelsdorp DJ, Evans D, Saegerman S, Mullin C, Haubruge E, Nguyen BK, Frazier M, Frazier J, Cox-Foster D, Chen Y, Underwood R, Tarpy DR, Pettis JS. 2009. Colony Collapse Disorder: A Descriptive Study. PLoS ONE 4(8): e6481.doi: 10.1371/journal.pone.0006481.

Appendix A. Chemical Identity Table and Proposed Degradation Pathway

                                     Name
                                 Chemical Name
                                    SMILES
                                  CAS Number
                                   Structure
                                  Study Type
                                     MRID
                        Max % AR or Concentration (day)
                 Final % AR or  Concentration (Time interval)
Iprodione
3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidinecarboxa-mide

SMILES: c1c(Cl)cc(Cl)cc1N2C(=O)CN(C(=O)NC(C)C)C2(=O)

CAS No. 36734-19-7

Hydrolysis
418854-01
                                      --
82% (pH 5, Day 30)





                                      --
41% (pH 7, 125 hrs)





                                      --
5.6% (pH 9, 2 hrs)



Aqueous photolysis
418619-01[4]
                                      --
68% (Day 33)



Aerobic soil
430910-02
                                      --
0.75% (Day 276)



Aerobic soil
445905-01[1]
                                      --
6.85% (Day 100)



Aerobic aquatic
425038-01[3]
                                      --
7.8% (Day 30)



Anaerobic aquatic 
417558-01
                                      --
3.4% (Day 365)



Terrestrial field 
418774-01
                                      --
<0.01 ppm (Day 538)



Aquatic field (H2O)
Aquatic field (soil)
437183-01
                                      --
                                      --
0.008 ppm (Day 44)
0.007 ppm (Day 44)
RP32596
3,5-dichloroaniline
(3,5-DCA)

SMILES: Nc(cc(cc1CL)CL)c1

CAS No. 626-43-7

Aerobic soil
430910-02
9% (Day 30)
ND[7] (Day 276)



Aerobic soil
445905-01[1]
3.9% (Day 50)
ND[7] (Day 100)



Aerobic aquatic
425038-01
11.7% (Day 30)
11.7% (Day 30)



Anaerobic aquatic
417558-01
3.6% (Day 275)
2.4% (Day 365)



Aquatic field (H2O)
Aquatic field (soil)
437183-01
<0.005 ppm (Day 44)
<0.005 ppm (Day 44)
<0.005 ppm (Day 44)
<0.005 ppm (Day 44)
RP30228
3-(1-methylethyl)-N-(3,5-dichlorophenyl)-2,4-dioxo-1-imidazolidine-carboxamide

SMILES: c1c(CL)cc(CL)cc1NC(=O)N2CC(=O)N(C(C)(C))C2(=O)

CAS No. NA

Hydrolysis
418854-01
46% (pH 7, 125 hrs)
46% (pH 7, 125 hrs)





93% (pH 9, 2 hr)
93% (pH 9, 2 hr)



Aqueous photolysis
418619-01[4]
2.7% (Day 17)
2% (Day 33)



Aerobic soil
430910-02
6.9% (Day 14)
2% (Day 276)



Aerobic soil
445905-01[1]
29% (Day 30)
15% (Day 100)



Aerobic aquatic 
425038-01
65% (Day 14)
56% (Day 30)



Anaerobic aquatic 
417558-01
70% (Day 14)
21% (Day 365)



Terrestrial field 
418774-01
0.47 ppm (Day 28)
0.15 ppm (Day 538)



Aquatic field (H2O)
Aquatic field (soil)
437183-01
0.057 ppm (Day 2)
0.13 ppm (1 mon)
0.016 ppm (Day 44)
0.012 ppm (Day 44)
RP32490[1]
3-(3,5-dichlorophenyl)-2,4-dioxo-1-imidazolidine-carboxamide

SMILES: c1c(CL)cc(CL)cc1N2C(=O)CN(C(=O)N)C2(=O)

CAS No. NA
                                       
Aerobic soil
430910-02
0.28% (Day 1)
ND[7] (Day 276)



Aerobic aquatic
425038-01
15% (Day 1)
4% (Day 30)



Anaerobic aquatic
417558-01
8.4% (Day 30)
0.8% (Day 365)



Terrestrial field
418774-01
0.09 ppm (Day 7)
<0.01 ppm (Day 538)



Aquatic field (H2O)
Aquatic field (soil)
437183-01
0.006 ppm (Day 2)
<0.005 ppm (Day 44)
<0.005 ppm (Day 44)
<0.005 ppm (Day 44)
RP35606[1,2]
[(dichloro-3,5-phenyl)-1-isopropylcarbamoyl-3]-2-acetic acid

SMILES: c1c(CL)cc(CL)cc1NC(=O)N(CC(=O)(O))C(=O)NC(C)(C)

CAS No. NA

Hydrolysis
418854-01
12% (pH 5, Day 30)
12% (pH 5, Day 30)





10% (pH 7, 40 hrs)
5.5% (pH 7, 125 hrs)





2% (pH 9, 107 hrs)
2% (pH 9, 107 hrs)



Aerobic soil
430910-02
1.2% (Day 7)
ND[7] (Day 276)



Aerobic soil
445905-01[1]
1.7% (Day 7)
ND (Day 100)



Aerobic aquatic
419276-01
8.9% (Day 30)
8.9% (Day 30)
Bold indicates major degradate.
1. Analyzed for in aqueous photolysis study (MRID 418619-01), but not found.
2. Analyzed for in aerobic aquatic metabolism study (MRID 425038-01), but not found.

Proposed Degradation Pathway (Aerobic Soil Metabolism Study, MRID 430910-02)



Appendix B. BEAD USE and Usage Reports

                              Iprodione (109801)
                     Screening Level Usage Analysis (SLUA)
                            Date: January 31, 2012 
                                       
What is a Screening Level Usage Analysis (SLUA)?
 Available estimates of pesticide usage data for a particular active ingredient that is used on agricultural crops in the United States.
 Pesticide usage data obtained from various sources.  The data are then merged, averaged, and rounded so that the presented information is not proprietary, business confidential, or trade secret. 
What does it contain?
 Pesticide usage data for a single active ingredient only.
 Agricultural use sites (crops) that the pesticide is reported to be used on. 
 Available pesticide usage information from U.S. states that produce 80% or more of a crop, in most cases, or less than 80%, in rare cases, depending on the scope of the survey and available resources.
 Annual percent of crop treated (average & maximum) for each agricultural crop.
 Average annual pounds of the pesticide applied for each agricultural crop (i.e., for the states surveyed, not for the entire United States).
What assumptions can I make about the reported data?
 Average pounds of active ingredient applied - Values are calculated by merging pesticide usage data sources together; averaging across all observations, then rounding.  Note:  If the estimated value is less than 500, then that value is labeled <500.  Estimated values between 500 & <1,000,000 are rounded to 1 significant digit.  Estimated values of 1,000,000 or greater are rounded to 2 significant digits.)
 Average percent of crop treated - Values are calculated by merging data sources together; averaging by year, averaging across all years, & rounding to the nearest multiple of 5.  Note:  If the estimated value is less than 2.5, then the value is labeled <2.5.  If the estimated value is less than 1, then the value is labeled <1.
 Maximum percent of crop treated - Value is the single maximum value reported across all data sources, across all years, & rounded up to the nearest multiple of 5.  Note:  If the estimated value is less than 2.5, then the value is labeled <2.5.
What are the data sources used?
 USDA-NASS (United States Department of Agriculture's National Agricultural Statistics Service)  -  pesticide usage data from 2003 to 2010.
 Private pesticide market research  -  pesticide usage data from 2003 to 2010.
 California Department of Pesticide Regulation (DPR) Pesticide Use Reporting (PUR) data for 2003 to 2009.
What are the limitations to the data?
 Additional registered uses may exist but are not included because the available surveys do not report usage (e.g., small acreage crops).
 Lack of reported usage data for the pesticide on a crop does not imply zero usage.
 Usage data on a particular site may be noted in data sources, but not quantified.  In these instances, the site would not be reported in the SLUA.
 Non-agricultural use sites (e.g., turf, post-harvest, mosquito control, etc.) are not reported in the SLUA.  A separate request must be made to receive these estimates.
 Some sites show some use, even though they are not on the label.  This usage could be due to various factors, including, but not limited to Section 18 requests, existing stocks of the chemical, data collection errors, and experimental use permits (EUPs).  	 
      
     Screening Level Estimates of Agricultural Uses of Iprodione (109801)
                             Sorted Alphabetically
                           Reported Years: 2003-2010
                                     Crop
                                   Pounds of
                                    Active
                                  Ingredient
                                Average Percent
                                   of  Crop
                                    Treated
                                    Maximum
                            Percent of Crop Treated




1
Almonds
     200,000
                                      45
                                      55
2
Apricots
       6,000
                                      45
                                      75
3
Beans, Green
      20,000
                                       5
                                      15
4
Blueberries
       1,000
                                       5
                                      10
5
Broccoli
        <500
                                     <1
                                    <2.5
6
Cabbage
       1,000
                                    <2.5
                                    <2.5
7
Caneberries
       2,000
                                       5
                                      20
8
Carrots
      20,000
                                      25
                                      40
9
Cauliflower
        <500
                                     <1
                                    <2.5
10
Cherries
      20,000
                                      15
                                      25
11
Cotton
       6,000
                                     <1
                                    <2.5
12
Dry Beans/Peas
       2,000
                                     <1
                                    <2.5
13
Garlic
       7,000
                                      10
                                      25
14
Grapes
       5,000
                                     <1
                                    <2.5
15
Lettuce
      70,000
                                      20
                                      35
16
Nectarines
       8,000
                                      30
                                      35
17
Onions
      40,000
                                      20
                                      30
18
Peaches
      20,000
                                      15
                                      25
19
Peppers
       1,000
                                     <1
                                    <2.5
20
Plums/Prunes
       7,000
                                      10
                                      25
21
Pluots *
        <500
                                      60
                                      70
22
Potatoes
      20,000
                                    <2.5
                                      10
23
Rice
       1,000
                                     <1
                                    <2.5
24
Spinach
       2,000
                                    <2.5
                                    <2.5
25
Strawberries
       2,000
                                       5
                                      10
26
Tobacco+
      20,000
                                    <2.5
                                    <2.5
All numbers rounded.
                                                                        <500
Less than 500 pounds of active ingredient
                                                                        <2.5
Less than 2.5 percent of crop treated
                                                                          <1
Less than 1 percent of crop treated
                                                                               

                                                                              *
Based on CA DPR data only (valid because 95% or more of U.S. acres grown are in California)
                                                                              +
Crops not known to be listed on active end use product registrations or as Section 18 emergency
exemptions when this report was run
	SLUA data sources include: 
  USDA-NASS (United States Department of Agriculture's National Agricultural Statistics Service) 
Private Pesticide Market Research
  California DPR (Department of Pesticide Regulation)
These results reflect amalgamated data developed by the Agency and are releasable to the public.


BEAD Use Report for Iprodione

Appendix C. OPPIN Bibliography

(a) Environmental Fate Studies

	Guideline:  63-0      Reports of Multiple Physical/chemical Characteristics

MRID:  41230503
Weiler, D.; Russell, D.; Oden, K. (1988) Vapor Pressure Determination of Iprodione: Report No. 40426.  Unpublished study prepared by Rhone-Poulenc Ag Co.  22 p.

MRID:  47778802
Miller, R. (2009) Product Properties: Color, Physical State, Odor, Stability to Normal and Elevated Temperatures, Oxidation/Reduction: Chemical Incompatibility, pH, UV/Visible Absorption, Melting Point/Melting Range, Density, Partition Coefficient (n-Octanol/Water), Water Solubility, and Vapor Pressure (Iprodione Technical).  Project Number: CHB/EX/609/011/P/1.  Unpublished study prepared by PhibroWood, LLC.  37 p.

	Guideline:  161-1      Hydrolysis

MRID:  00059481
Laurent, M.; Buys, M.; Charassol, Y.; et al. (1976) 26 019 R.P.: Degradation in Water: R.P./R.D./C.N.G.-An--Report no. 3036.  (Translation; unpublished study received May 24, 1977 under 359-EX-55; prepared by Societe des Usines Chimiques Rhone- Poulenc, submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:230241-F) 

MRID:  00068287
Laurent, M.; Buys, M.; Aublet, ?; et al. (1976) 26019 R.P.: Solubility and Stability in Water: S.U.C.R.P.-- D.S.An. Nord. No. 2585.  (Translation; unpublished study received Jan 24, 1977 under 359-EX-55; prepared by Societe des Usines Chimiques Rhone-Poulenc, France, submitted by Rhone- Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:227614-E) 

MRID:  41885401
Das, Y. (1990) Hydrolysis of ?Phenyl(U)-?carbon 14||Iprodione in Aqueous Solutions Buffered at pH 5, 7 and 9: Lab Project Number: 89100.  Unpublished study prepared by Innovative Scientific Services, Inc.  96 p.
      
	Guideline:  161-2      Photodegradation-water

MRID:  41861901
Adrian, P.; Robles, J. (1991) Carbon 14-Iprodione: Aqueous Photolysis: Lab Project Number: 90/22: AG/CBLD/AN/9115524.  Unpublished study prepared by Rhone-Poulenc Secteur Agro.  97 p. 

MRID:  42201301
Adrian, P.; Robles, J. (1992) Carbon 14-Iprodione Aqueous Photolysis Addendum to MRID No. 41861901: Lab Project Number: 90-22.  Unpublished study prepared by Rhone-Poulenc Secteur Agro.  13 p.

	Guideline:  161-3      Photodegradation-soil

MRID:  41912101
Ayliffe, J.; Outram, J.; Reeves, G. (1991) Iprodione-?carbon 14|: Soil Photolysis Study: Lab Project Number: P91/048.  Unpublished study prepared by Rhone-Poulenc Agric., Ltd.  86 p. 

MRID:  42897101
John, A.; French, N.; Lowden, P. (1993) Fungicides: (Carbon 14) Iprodione: Soil Photolysis: Lab Project Number: P93/073. Unpublished study prepared by Rhone-Poulenc Agriculture Ltd. 128 p.

	Guideline:  162-1      Aerobic soil metabolism

MRID:  43091002
Waring, A. (1993) (carbon 14)--Iprodione: Aerobic Soil Metabolism: Final Report: Lab Project Number: 68/132: 68/132-1015.  Unpublished study prepared by Hazleton Europe. 105 p. 

MRID:  44590501
Waring, A. (1993) (carbon 14)-Iprodione: Soil Degradation: Final Report: Lab Project Number: 68/139-1015.  Unpublished study prepared by Hazleton UK.  73 p. 

MRID:  45239201
Quarmy, D. (2000) Iprodione Metabolite: (carbon-14)-3,5-Dichloroaniline Aerobic Soil Metabolism: Lab Project Number: 99R16743.  Unpublished study prepared by Springborn Laboratories, Inc.  282 p. 

	Guideline:  162-3      Anaerobic aquatic metabolism

MRID:  00162220
Thomas, R.; Cunningham, W. (1983) Anaerobic Aquatic Metabolism of [Carbon 14]-RP-26019: Final Report: Project No. 3/2202.  Unpublished study prepared by Borriston Laboratories, Inc.  35 p. 

MRID:  41600201
Spare, W. (1989) Aerobic Aquatic Metabolism of Iprodione: Final Report: Project Number: 1509.  Unpublished study prepared by Agrisearch Inc.  4 p. 

MRID:  41755801
Spare, W. (1990) Anaerobic Aquatic Metabolism of Iprodione: Lab Project Number: 1510.  Unpublished study prepared by Agrisearch Inc.  114  p. 

MRID:  42854101
Spare, W. (1993) Anaerobic Aquatic Metabolism of Iprodione: Supplemental: Lab Project Number: 1510.  Unpublished study prepared by Agrisearch Inc.  55 p.

	Guideline:  162-4      Aerobic aquatic metabolism

MRID:  00162219
Thomas, R.; Fletcher, C. (1983) Aquatic Metabolism of [Carbon 14]- RP-26019: Project No. 3-2201.  Unpublished study prepared by Borriston Laboratories, Inc.  41 p. 

MRID:  41927601
Spare, W. (1991) Aerobic Aquatic Metabolism of Iprodione: Lab Project Number: 1514.  Unpublished study prepared by Agrisearch Inc.  147 p. 
MRID:  42503801
Spare, W. (1992) Aerobic Aquatic Metabolism of Iprodione: Supplemental Report ?MRID #41927601|: Lab Project Number: 1514. Unpublished study prepared by Agrisearch Inc.  117 p. 

MRID:  44605001
Purser, D. (1992) (Carbon 14)-Iprodione: Degradation and Retention in Water/Sediment Systems: Amended Final Report: Lab Project Number: 68/113: 7397: P6876D.  Unpublished study prepared by Hazleton UK.  160 p. 
      
      Guideline:  163-1      Leaching/adsorption/desorption

MRID:  00059479
Gouot, J.M.; Lacroix, L.; Sauli, M.; et al. (1976) A Study to Investigate the Leaching of 26 019 R.P. in Soil, Using ^14IC- Labelled 26 019 R.P.: R.P./R.D./C.N.G.-An no. 18845.  (Translation; unpublished study received May 24, 1977 under 359-EX- 55; prepared by Societe des Usines Chimiques Rhone-Poulenc, submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:230241-D) 

MRID:  00068286
Gouot, J.M.; Lacroix, L; Sauli, M.; et al. (1976) A Study To Investigate the Leaching of 26 019 R.P. in Soil, Using (14C)-Labelled 26 019 R.P.  (Translation; unpublished study received Jan 24, 1977 under 359-EX-55; prepared by Rhone-Poulenc, France, submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL: 227614-D) 

MRID:  41878801
Outram, J.; Reeves, G.; Smith (1991) Iprodione-?Carbon 14|: Adsorption/Desorption on Four Soils: Lab Project Number: P91-049.  Un- published study prepared by Rhone-Poulenc Ag. Ltd.  87 p. 

MRID:  41889601
Doble, M.; Outram, J.; Reeves, G. (1991) Iprodione-[carbon 14]: Aged Leaching Study with Four Soils: Lab Project No: P91/050. Unpublished study prepared by Rhone-Poulenc Agric., Ltd.  78 p. 

MRID:  43349201
Newby, S.; Ayliffe, J.; Jones, M. (1994) Iprodione: Aged Leaching Study in Four Soils: Lab Project Number: P 94/013. Unpublished study prepared by Rhone-Poulenc Agriculture Ltd. 107 p. 

MRID:  43349202
Burr, C.; Newby, S. (1994) Iprodione: Adsorption/Desorption to and from Four Soils and an Aquatic Sediment: Lab Project Number: P94/014.  Unpublished study prepared by Rhone-Poulenc Agriculture Ltd.  81 p.

MRID:  45114101
Feung, C. (1999) Iprodione Metabolite: (carbon-14)-3,5-Dichloroaniline Soil Adsorption/Desorption Study: Lab Project Number: 99R16744.  Unpublished study prepared by Rhone Poulenc Ag Company.  165 p. 
	
	Guideline:  164-1      Terrestrial field dissipation

MRID:  00059484
Rhodia, Incorporated (1976) RP 26019 and Metabolites: Residue Study in/on Turf Soil: Report No. 76/069/NB/AG.  (Unpublished study received May 24, 1977 under 359-EX-55; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:230241-I) 

MRID:  00068290
Rhodia, Incorporated (1976) RP 26019 and Metabolites: Residue Study in/on Turf Soil, 1976 Program: Lab. Ref. No. 76/069/NB/AG. (Unpublished study received Jan 24, 1977 under 359-EX-55; sub- mitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:227614-I) 

MRID:  00162218
Gemma, A.; Heinzelmann, G.; Wargo, J. (1986) Iprodione Aquatic Field Dissipation and Field Irrigated Crop Study.  Unpublished study prepared by Rhone-Poulenc Inc.  300 p. 

MRID:  41877401
Norris, F. (1991) A Terrestrial Field Soil Dissipation Study with Iprodione: Lab Project Number: 40644: EC/P-89-0013.  Unpublished study prepared by Rhone-Poulenc Ag Co.; A & L Eastern Agricultural Labs, Inc.; Morse Labs., Inc.  275 p.

MRID:  43718302
Citation:  Hudson, J. (1995) Validation of Method of Analysis for Iprodione (RP26019) and its Metabolites (RP32490, RP32596, RP36221, and RP30228) in Soil: Final Report: Lab Project Number: EC-94-258: EC-95-298: EC-95-296.  Unpublished study prepared by Rhone-Poulenc Ag Co.  180 p. 

	

      Guideline:  164-2      Aquatic field dissipation

MRID:  43718301
Chancey, E. (1995) An Aquatic Field Dissipation Study with Iprodione: Lab Project Number: 44729: EC-92-187: FAD-IPR-RI-MS-92.  Unpublished study prepared by Rhone-Poulenc Ag Co.; Agvise, Inc.; and South Texas Ag Research Inc.  374 p. 

MRID:  45239203
Citation:  Carringer, S. (1999) Iprodione: Validation of Method of Analysis of Iprodione and its Metabolites RP 30228 and RP 32596 in Ground Water: Final Study Report: Lab Project Number: EC-98-432: 45593.  Unpublished study prepared by Rhone-Poulenc Ag Company and Agvise Laboratories.  123 p. {OPPTS 850.7100} 

MRID:  45239204
Citation:  Sweeney, R. (1999) Independent Laboratory Validation of Method of Analysis for Iprodione and its Metabolites RP 30228 and RP 32596 in Ground Water According to Ecological Effects Test Guidelines OPPTS 850.7100: Lab Project Number: 45380: 99R17181: ACFS-45380.  Unpublished study prepared by ABC Laboratories, Inc.  72 p. {OPPTS 850.7100} 

	Guideline:  165-4      Bioaccumulation in fish

MRID:  00162221
McAllister, W.; Bunch, B.; Burnett, J. (1986) Bioconcentration and Depuration of [Carbon 14]-Iprodione by Crayfish (Procambarus simulans, Faxon) under Static Uptake Conditions with a Treated Soil Substrate: Final Bioconcentration Report No. 33438.  Unpublished study prepared by Analytical Bio-Chemistry Laboratories, Inc.  297 p. 

MRID:  00162222
Gemma, A.; Heinzelmann, G.; Wargo, J. (1986) Identification of Iprodione Residues in Crayfish.  Unpublished study prepared by Rhone-Poulenc Inc.  23 p. 

MRID:  43091001
Pottinger, T. (1994) Final Report: A Fish Bioaccumulation and Depuration Study on Iprodione: Lab Project Number: FH-OECD-34FT/BR: 68/134-1011R.  Unpublished study prepared by Windermere Laboratory, Institute of Freshwater Ecology.  172 p.

 (b) Ecological Effects Studies

      Guideline:  71-1      Avian Single Dose Oral Toxicity

MRID:  48589
McGinnis, C.H., Jr.; Johnson, C.A. (1973) The Determination of the Acute Oral LDI50^ in Bobwhite Quail for 26019 RP: Research Report No. CHM 73:93.  (Unpublished study received Jan 24, 1977 under 359-EX-55; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:227615-K) 

MRID:  48590
McGinnis, C.H., Jr.; Johnson, C.A. (1974) The Determination of the Acute Oral LDI50^ in Mallard Ducks for 26019 RP: Research Report No. CHM 74:49.  (Unpublished study received Jan 24, 1977 under 359-EX-55; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:227615-L) 

MRID:  41604101
Culotta, J.; Hoxter, K.; Smith, G. et al. (1990) Iprodione: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: 171-120.  Unpublished study prepared by Wildlife International Ltd.  43 p. 

      Guideline:  71-2      Avian Dietary Toxicity

MRID:  48591
McGinnis, C.H., Jr.; Johnson, C.A. (1974) The Effects of Dietary 26019 R.P. and Technical Dieldrin on Young Mallard Ducks--an 8 Day Subacute Toxicity Test: Research Report No. CHM 74:64. (Unpublished study received Jan 24, 1977 under 359-EX-55; sub- mitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:227615-M) 

MRID:  48592
McGinnis, C.H., Jr.; Johnson, C.A. (1974) The Effects of Dietary 26019 RP and Technical Dieldrin on Young Bobwhite Quail--a 12 Day Subacute Toxicity Test: Report No. CMH 74:14.  (Unpublished study received Jan 24, 1977 under 359-EX-55; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL: 227615-N) 

MRID:  68740
McGinnis, C.H., Jr.; Johnson, C.A. (1974) The Effects of Dietary 26019 RP and Technical Dieldrin on Young Bobwhite Quail--A 12 Day Subacute Toxicity Test: Report No. CHM 74.14.  (Unpublished study received Jan 13, 1978 under 359-684; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL: 232703-J) 

MRID:  68741
McGinnis, C.H., Jr.; Johnson, C.A. (1974) The Effect of Dietary 26 019 RP on Body Weight, Feed Consumption, Reproduction and the Production of 26 019 RP Residues in Body Tissues and Eggs of Bobwhite Quail: Research Report No. CHM 74:105.  (Unpublished study received Jan 13, 1978 under 359-684; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL: 232703-K) 

MRID:  86839
Fink, R.; Beavers, J.B.; Joiner, G.; et al. (1980) Final Report: Subacute Feeding--Reproduction Screening Bioassay--Bobwhite Quail: Iprodione Technical: Project No. 171-101.  (Unpublished study received Oct 26, 1981 under 46153-1; prepared by Wildlife International, Ltd., submitted by Precision Compounding, Inc., Newark, N.J.; CDL:246150-A) 

MRID:  41604102
Driscoll, C.; Foster, J.; Hoxter, K. et al. (1990) Iprodione Technical: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 171-118.  Unpublished study prepared by Wildlife International Ltd.  73 p. 

MRID:  41604103
Driscoll, C.; Foster, J.; Hoxter, K. et al. (1990) Iprodione Technical: A Dietary LC50 Study with the Mallard: Lab Project Num- ber: 171-119.  Unpublished study prepared by Wildlife International Ltd.  73 p. 

      Guideline:  71-4      Avian Reproduction

MRID:  68741
McGinnis, C.H., Jr.; Johnson, C.A. (1974) The Effect of Dietary 26 019 RP on Body Weight, Feed Consumption, Reproduction and the Production of 26 019 RP Residues in Body Tissues and Eggs of Bobwhite Quail: Research Report No. CHM 74:105.  (Unpublished study received Jan 13, 1978 under 359-684; submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL: 232703-K) 

MRID:  86840
Fink, R.; Beavers, J.B.; Joiner, G.; et al. (1981) Final Report One-generation Reproduction Study--Mallard Duck: Iprodione Technical: Project No. 171-103.  (Unpublished study received Oct 26, 1981 under 46153-1; prepared by Wildlife International, Ltd., and Rhone-Poulenc, Inc., submitted by Precision Compounding, Inc., Newark, N.J.; CDL:246150-C) 

MRID:  99126
Fink, R.; Beavers, J.B.; Joiner, G.; et al. (1981) Final Report: One-generation Reproduction Study--Bobwhite Quail: Iprodione Technical: Project No. 171-102.  (Unpublished study received Oct 26, 1981 under 46153-1; prepared by Wildlife International, Ltd. and Rhone-Poulenc, Inc., submitted by Precision Compound- ing, Inc., Newark, N.J.; CDL:246150-B) 

MRID:  92083002
Gregg, B. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 00099126.  Iprodione - One-generation Reproduction Study - Bobwhite Quail: Project 171-102.  Prepared by WILDLIFE INTERNATIONAL LTD. 36 p. 

MRID:  92083003
Gregg, B. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 00086840.  Iprodione - One-generation Reproduction Study - Mallard Duck: Project 171-103.  Prepared by WILDLIFE INTERNATIONAL. 37 p. 

Guideline:  72-1      Acute Toxicity to Freshwater Fish

MRID:  70148
Calmbacher, C.W.; Vilkas, A.G. (1978) The Acute Toxicity of RP26019 Technical (Assay 95.06%, Lot #77103-01) to the Bluegill Sunfish (~Lepomis macrochirus~Rafinesque): UCES Proj. No. 11506-48-02. (Unpublished study received Sep 1, 1978 under 359-684; prepared by Union Carbide Corp., submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:234810-A) 

MRID:  70149
Calmbacher, C.W.; Vilkas, A.G. (1978) The Acute Toxicity of RP26019 Technical (Assay 95.06%, Lot #77103-01) to the Rainbow Trout (~Salmo gairdneri~Richardson): UCES Proj. No. 11506-48-03. (Unpublished study received Sep 1, 1978 under 359-684; prepared by Union Carbide Corp., submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:234810-B) 

MRID:  162223
McAllister, W.; Bunch, B. (1986) Dynamic Acute Toxicity of Iprodione Technical to Juvenile Crayfish (Procambarus simulans, Faxon): Flow-through Acute Toxicity Report #33434.  Unpublished study prepared by Analytical Bio-Chemistry Laboratories, Inc. 148 p. 

MRID:  162224
Swigert, J.; Franklin, B.; Seidel, A.; et al. (1986) Acute Flow- through Toxicity of Iprodione Technical to Channel Catfish (Ictalurus punctatus): Report #34385.  Unpublished study pre- pared by Analytical Bio-Chemistry Laboratories, Inc.  109 p. 

MRID:  40489203
Surprenant, D. (1987) Acute Toxicity of Rovral 50 WP to Bluegill (Lepomis macrochirus) under Flow-through Conditions: SLS Report #87-12-2578: SLS Study #10566.1087.6111.105.  Unpublished study prepared by Springborn Life Sciences, Inc.  47 p. 

MRID:  41604104
Sousa, J. (1990) Iprodione Technical: Acute Toxicity to Bluegill sunfish (Lepomis macrochirus) under Flow-Through Conditions: Lab Project Number: 90-5-3329: 10566.1089.6140.105.  Unpublished study prepared by Springborn Laboratories, Inc.  55 p. 

MRID:  41604105
Sousa, J. (1990) Iprodione Technical: Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) under Flow-through Conditions: Lab Project Number: 90-5-3331: 10566.1089.6139.108.  Unpublished study prepared by Springborn Laboratories, Inc.  54 p. 

MRID:  92083004
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40489203.  Acute Toxicity of ROVRAL 50 WP to Bluegill (Lepomis macrochirus) under Flow-through Conditions: Project 87-12-2578. Prepared by Springborn Life Sciences Inc. 16 p. 

MRID:  92083069
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 00162224.  Iprodione - Acute Flow-through Toxicity: Channel Catfish (Ictalurus punctatus): Project 34385.  Prepared by ANALYTICAL BIO-CHEMISTRY LABORATORIES. 16 p. 

MRID:  92083070
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 00162223.  Iprodione - Acute Flow-through Toxicity: Juvenile Crayfish (Procambarus simulans, Faxon): Project 33434.  Prepared by ANALYTICAL BIO-CHEMISTRY LABORATORIES. 16 p. 

      Guideline:  72-2      Acute Toxicity to Freshwater Invertebrates

MRID:  68738
Ambrosi, D.; Desmoras, J.; LaCroix, L. (1977) Fungicides: Toxicity of R.P. 26 019 to Daphnia (~Daphnia pulex~): R.P./R.D./ C.N.G. No. 19 168.  (Unpublished study received Jan 13, 1978 under 359-684; prepared by Rhone-Poulenc, France, submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL: 232703-F) 

MRID:  68739
Roberts, S.; Parke, G.S.E. (1977) Report: 48-hour Static LC50 of RP 26019 Technical in~Daphnia magna~: Laboratory No. 7E-8445. (Unpublished study received Jan 13, 1978 under 359-684; pre- pared by Cannon Laboratories, Inc., submitted by Rhone-Poulenc, Chemical Co., Monmouth Junction, N.J.; CDL:232703-G) 

MRID:  79633
Vilkas, A.G. (1977) The Acute Toxicity of RP 26019 Technical to the Water Flea~Daphnia magna~Straus: UCES Proj. # 11506-48-01. (Unpublished study received Jan 13, 1978 under 359-684; pre- pared by Union Carbide Corp., submitted by Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:232703-H) 

MRID:  40489206
Surprenant, D. (1988) Acute Toxicity of Rovral 50 WP to Daphnids (Daphnia magna) under Flow-through Conditions: Report #87-12- 2597: SLS Study #10566.1087.6112.115.  Unpublished study pre- pared by Springborn Life Sciences, Inc.  47 p. 


MRID:  41642001
McNamara, P. (1990) Iprodione Technical--Acute Toxicity to Daphnids (Daphnia magna) during a 48-Hour Flow-through Exposure: Final Report: Lab Project Number: 90-7-3380: 10566.1086.6138.115.  Unpublished study prepared by Springborn Laboratories, Inc.  6 p. 

MRID:  92083005
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40489206.  Acute Toxicity of ROVRAL 50 WP to (Daphnia magna) under Flow- through Conditions: Project 87-12-2597.  Prepared by SPRINGBORN LIFE SCIENCES, INC. 17 p. 


      Guideline:  72-3      Acute Toxicity to Estuarine/Marine Organisms

MRID:  40489202
Surprenant, D. (1987) Acute Toxicity of Iprodione Technical to Eastern Oysters (Crassostrea virginica) under Flow-through Conditions: SLS Report #87-12-2584: SLS Study #10566.1087.6115.504. Unpublished study prepared by Springborn Life Sciences, Inc.  45 p. 

MRID:  40489204
Surprenant, D. (1987) Acute Toxicity of Iprodione Technical to Mysid Shrimp (Mysidopsis bahia) under Flow-through Conditions: SLS Report #87-12-2580: SLS Study #10566.1087.6113.515.  Unpublished study prepared by Springborn Life Sciences, Inc.  45 p. 

MRID:  40489205
Surprenant, D. (1988) Acute Toxicity of Iprodione Technical to Sheepshead Minnow (Cyprinodon variegatus) under Flow-through Conditions: SLS Report #87-11-2583: SLS Study #10566.1087.6114. 505.  Unpublished study prepared by Springborn Life Sciences, Inc.  44 p. 

MRID:  42169301
Surprenant, D. (1991) Response to EPA FIFRA 88 Phase 4 Data Call-in on Iprodione (...)--Acute Toxicity to Mysid Shrimp: Lab Project Number: EMM1/2/92.  Unpublished study prepared by Springborn Labs., Inc.  6 p. 

MRID:  92083006
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40489205.  Acute Toxicity of Iprodione Technical to Sheepshead Minnow (Cyprinodon variegatus) under Flow-through Conditions: Project 87-12-2583.  Prepared by SPRINGBORN LIFE SCIENCES, INC. 17 p. 

MRID:  92083007
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40489202.  Acute Toxicity of IPRODIONE Technical to Eastern Oysters (Crassostrea virginica) under Flow-through Conditions: Project 87-12-2584.  Prepared by SPRINGBORN LIFE SCIENCES, INC. 19 p. 

MRID:  92083008
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40489204.  Acute Toxicity of Iprodione Technical to Mysid Shrimp (Mysidopsis bahia) under Flow-through Conditions: Project 87-12-2580.  Prepared by SPRINGBORN LIFE SCIENCES, INC. 17 p. 

      Guideline:  72-4      Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

MRID:  48593
Rausina, G.; McCollum, K.; Goode, J.W.; et al. (1974) Report to Rhodia, Inc., Chipman Division: Four-Day Static Fish Toxicity Studies with RP26019 Technical in Rainbow Trout, Bluegills, and Channel Catfish: IBT No. 621-05132.  (Unpublished study received Jan 24, 1977 under 359-EX-55; submitted by Rhone- Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:227615-O) 

MRID:  40489201
Surprenant, D. (1988) The Chronic Toxicity of Iprodione Technical to Daphnia magna under Flow-through Conditions: Report #87-12- 2573: Study #10566-1087-6116-130.  Unpublished study prepared by Springborn Life Sciences, Inc.  59 p. 

MRID:  40550801
Surprenant, D. (1988) The Toxicity of Iprodione Technical to Fathead Minnow (Pimephales promelas) Embryos and Larvae: Rept. No. 88-2-2639.  Unpublished study prepared by Springborn Life Sciences, Inc.  59 p. 

MRID:  40550802
Surprenant, D. (1988) Chronic Toxicity of Iprodione Technical to Mysid Shrimp (Mysidopsis bahia): Report #88-3-2640.  Unpublished study prepared by Springborn Life Sciences, Inc.  64 p. 

MRID:  40832201
Surprenant, D. (1988) Chronic Toxicity of Iprodione Technical to Mysid Shrimp (Mysidopsis bahia): Supplement Study: Report #88-6- 2761: Study #10566.0388.6117.530.  Unpublished study prepared by Springborn Life Sciences, Inc.  65 p. 

MRID:  92083009
Gregg, B. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40550801.  Iprodione - Toxicity to Fathead Minnow (Pimephales promelas) Embryos and Larvae - Project 88-2-2639.  Prepared by SPRINGBORN LIFE SCIENCES, INC. 20 p. 

MRID:  92083010
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40489201.  The Chronic Toxicity of IPRODIONE Technical to Daphnia magna under Flow-through Conditions: Project 87-12-2573. Prepared by SPRINGBORN LIFE SCIENCES, INC. 22 p. 

MRID:  92083011
Mihaich, E. (1990) Rhone-Poulenc Ag Company Phase 3 Summary of MRID 40832201.  The Chronic Toxicity of IPRODIONE Technical to Mysid Shrimp (Mysidopsis bahia): Project 88-6-2761.  Prepared by SPRINGBORN LIFE SCIENCE, INC. 23 p. 

      Guideline:  81-1      Acute oral toxicity in rats

MRID:  42306301
Cummins, H. (1989) Iprodione: Acute Oral Toxicity Study in the Rat: Lab Project Number: RHA/255: 89/RHA255/0391.  Unpublished study prepared by Life Science Research Ltd.  46 p. 


      Guideline:  81-3      Acute inhalation toxicity in rats

MRID:  42946101
Nachreiner, D. (1993) Iprodione: Acute Dust Inhalation Toxicity Study in Rats: Lab Project Number: 93N1216.  Unpublished study prepared by Bushy Run Research Center, Union Carbide.  58 p. 

      Guideline:  83-4      2-generation repro.-rat

MRID:  41871601
Henwood, S. (1991) Two-generation Reproduction Study with Iprodione Technical in Rats: Final Report: Lab Project Id.: HLA 6224-154. Prepared by Hazleton Laboratories America, Inc. 1669 p. 

      Guideline:  122-2      Aquatic plant growth

MRID:  41604108
Giddings, J. (1990) Iprodione Technical: Toxicity to the Duckweed Lemna gibba G3: Lab Project Number: 90-06-3351: 10566.1089.614. 410.  Unpublished study prepared by Springborn Laboraotries, Inc.  40 p. 

      Guideline:  123-2      Aquatic plant growth

MRID:  41604107
Giddings, J. (1990) Iprodione Technical: Toxicity to the Freshwater Green Alga Selenastrum Capricornutum: Final Report: Lab Project Number: 90-06-3346: 10566-1089-6141-430.  Unpublished study pre- pared by Springborn Laboratories, Inc.  50 p. 

MRID:  41604109
Giddings, J. (1990) Iprodione Technical: Toxicity to the Marine Diatom Skeletonema Costatum: Lab Project Number: 90-06-3347: 10566.1089.6141.450.  Unpublished study prepared by Springborn Laboratories, Inc.  50 p. 

MRID:  41604110
Giddings, J. (1990) Iprodione Technical: Toxicity to the Freshwater Bluegreen Alga Anabaena Flos-Aquae: Lab Project Number: 90-05- 3338: 10566-1089-6141-420.  Unpublished study prepared by Springborn Laboratories, Inc.  47 p. 

MRID:  41604111
Giddings, J. (1990) Iprodione Technical: Toxicity to the Freshwater Diatom Navicula Pelliculosa: Final Report: Lab Project Number: 90-6-3340: 10566-1089-6141-440.  Unpublished study prepared by Springborn Laboratories, Inc.  49 p. 

MRID:  43575601
Suprenant, D. (1995) Supplement Data for: Iprodione Technical: Toxicity to the Freshwater Diatom Navicula pelliculosa. Addendum to MRID No. 41604111: Lab Project Number: 90/6/3340: 10566/1089/6141/440.  Unpublished study prepared by Springborn Laboratories Inc.  12 p. 

MRID:  45741301
Sowig, P. (2002) Duckweed (Lemna gibba G3) Growth Inhibition Test Iprodione; Substance, Technical: Lab Project Number: CE02/033: C022577.  Unpublished study prepared by Aventis CropScience GmbH.  47 p.

Appendix D. SIP/STIR Model Results

(a) SIP Model Output






(b) STIR Model Output


Appendix E. IDS Aggregate Incident Report for Iprodione


Appendix F. Data Call-In Justification Tables for Non-guideline/Degradate Studies and 

Study Title:  Honeybee Larval Toxicity Study
Guideline Number:  Non-guideline
Test Substance:  Iprodione -- TGAI
                       Rationale for Requiring the Data
Incident data suggest that iprodione may adversely affect honeybee (Apis mellifera) brood (larval and pupal) development. In an unpublished manuscript submitted as an incident report, increased mortality as well as abnormal morphological development occurred in female (worker) bee pupae. Although iprodione is practically non-toxic to adult worker bees on an acute contact exposure basis, a larval toxicity study is needed to determine the toxicity of the compound to developing brood. In addition, iprodione has been reported to occur in bee colony wax (comb) samples, where it could potentially affect development of young. Submitted studies of iprodione do not provide information on the potential toxicity to developing honeybee brood. Therefore, a non-guideline honeybee larval toxicity study is recommended. The registrant should submit a proposed protocol for review and approval by EFED prior to initiation of the study.
                         Practical Utility of the Data
How will the data be used?
Data will be used to assess risk to non-target listed and non-listed terrestrial invertebrate species. This study would allow the Agency to refine the screening-level hazard assessment for beneficial terrestrial invertebrates.  The effects data will be used to determine the potential for adverse effects on beneficial terrestrial invertebrates through direct effects on larval bees.  

How could the data impact the Agency's future decision-making?
EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action it authorizes or takes "...is not likely to jeopardize the continued existence of any endangered or threatened species or result in the destruction or adverse modification of critical habitat" and "to use the best scientific data available" in carrying out this obligation. The data EPA intends to call in are necessary to inform the determination required by ESA as to whether continued registration of a pesticide is or is not likely to jeopardize the species or its designated critical habitat. The lack of these data will limit the flexibility that the Agency has in coming into compliance with ESA and could result in use restrictions that are unnecessarily severe. In addition, the lack of these data may result in an uncertain assumed risk and potential mitigation of iprodione formulations under FIFRA.




Study Title:  Daphnid Reproduction Study
Guideline Number:  850.1300
Test Substance:  3,5-Dichloroaniline
                       Rationale for Requiring the Data
3,5-DCA (RP32596) is considered a degradate of concern of iprodione. Since 3,5-DCA likely has a different mode of action in ecological receptors as compared to iprodione, it will be assessed separately during risk assessment. No ecological effects data have been submitted for 3,5-DCA. EFED is recommending that a chronic reproduction study with Daphnia be carried out with 3,5-DCA to provide some information on the toxicity of this degradate to aquatic organisms. The results of this study would provide information on the relative toxicity of 3,5-DCA to iprodione, which would help determine whether 3,5-DCA is of toxicological concern for risk assessment. Results from this study would also serve as a basis for comparing the toxicity of 3,5-DCA to p-chloroaniline and 3,4-DCA, which would indicate whether these chemicals are suitable toxicity surrogates for estimating risks from 3,5-DCA. The justification for requesting a chronic rather than an acute toxicity study to represent 3,5-DCA is because the slow rate of degradation of 3,5-DCA in soil metabolism studies indicates that it is of chronic concern.
                         Practical Utility of the Data
How will the data be used?
Data will be used to compare toxicity of 3,5-DCA to the parent compound (iprodione) and potentially to calculate separate risk quotients for 3,5-DCA during risk assessment. 

How could the data impact the Agency's future decision-making?
This data will provide information on relative toxicity between a degradate (3,5-DCA) and its parent compound (iprodione). Since this data may be used to evaluate this degradate separately from the parent during risk assessment, such data may generally help inform how risk assessors evaluate degradates as residues of concern in risk assessment.  

