### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb**  **I. Studies to be Called**  **- In:** GuidelineNumbera40CFR158CitationbDataRequirementStudytypecAverageTestCostTotalPaperworkBurdenCostdTotalPaperworkBurdenHourse

835.1230 158.1300 Leaching and adsorption/desorption

– sediment leaching and soil adsorption/desorption EF $23,750.00 $8,313.00 105 835.1240 158.1300 Leaching and adsorption/desorption

– soil column leaching EF $46,780.00 $16,373.00 208 835.2120 158.1300 Hy drolysis EF $25,230.00 $8,831.00 112 835.4100 158.1300 Aerobic soil metabolism EF $94,375.00 $33,031.00 419 835.4200 158.1300 Anaerobic soil metabolism EF $71,300.00 $24,955.00 316 835.4300 158.1300 Aerobic aquatic metabolism EF $44,475.00 $15,566.00 197 835.6100 158.1300 Terrestrial field dissipation - storage stability in soil portion only EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry - analytical method for soil and associated independent laboratory validation EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry - analytical method for water and associated independent laboratory validation EF $22,000.00 $7,700.00 98 850.1075 158.630 Acute toxicity estuarine and marine organisms

– estuarine/marine fish (DPX - MP062) EE $11,576.00 $4,051.00 51 850.2100 158.630 Avian oral toxicity (DPX - MP062) EE $10,100.00 $3,535.00 45 850.4100 158.660 Terrestrial plant toxicity s eedling emergence (TEP with DPX - MP062) EE $20,375.00 $7,131.00 90 850.4100 158.660 Terrestrial plant toxicity s eedling emergence (TEP with DPX - KN128) EE $20,375.00 $7,131.00 90 850.4150 158.660 Terrestrial plant toxicity, v egetative vigor (TEP with DPX MP062) EE $24,500.00 $8,575.00 109 850.4150 158.660 Terrestrial plant toxicity with v egetative vigor (TEP with DPX - KN128) EE $24,500.00 $8,575.00 109 Non - GDLN 158.75 Larval honey bee acute oral toxicity (DPX - MP062) SS $36,000.00 $12,000.00 160 Non GDLN 2,3 158.630 (ORD Study Method EPA 600/R - 099 - 064) Chronic Freshwater Sediment Testing Flowthrough: (Hyallela azteca) EE $110,000.00 $38,500.00 488 Non GDLN 2,3 158.630 (ORD Study Method: EPA 600/R - 099 - 064) Chronic Freshwater Sediment Testing Flowthrough: (Chironomus dilutus or C. tentans) EE $110,000.00 $38,500.00 488 Non GDLN 2,3 158.630 (ORD Study Method: EPA 600/R - 099 - 020) Chronic Estuarine/Marine Sediment Testing Flowthrough: (Leptocheirus plumulosus) EE $110,000.00 $38,500.00 488

**Studies required for Indoxacarb degradates**  835.2120 158.1300 Hy drolysis (IN - JT333) EF $25,230.00 $8,831.00 112 835.2120 158.1300 Hy drolysis (IN - MP819) EF $25,230.00 $8,831.00 112 835.4100 158.1300 Aerobic soil metabolism (IN - JT333) EF $94,375.00 $33,031.00 419 835.4100 158.1300 Aerobic soil metabolism (IN - MP819) EF $94,375.00 $33,031.00 419 835.4300 158.1300 Aerobic aquatic metabolism (IN - JT333) EF $44,475.00 $15,566.00 197 835.4300 158.1300 Aerobic aquatic metabolism (IN - MP819) EF $44,475.00 $15,566.00 197 835.1230 158.1300 Leaching and adsorption/desorption

– sediment leaching and soil adsorption/desorption (IN - JT333) EF $23,750.00 $8,313.00 105 835.1230 158.1300 Leaching and adsorption/desorption

– sediment leaching and soil adsorption/desorption (IN - MP819) EF $23,750.00 $8,313.00 105 835.1240 158.1300 Leaching and adsorption/desorption

– soil column leaching (IN - JT333) EF $46,780.00 $16,373.00 208 835.1240 158.1300 Leaching and adsorption/desorption

– soil column leaching EF $46,780.00 $16,373.00 208

### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb**  (IN - MP819) 850.1075 158.630 Freshwater Fish Toxicity (Degradate IN - MP819) EE $11,957.00 $4,185.00 53 8 50 .6100 1 158.1300 Environmental chemistry for soil associated independent laboratory validation (IN - JT333) EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry for soil associated independent laboratory validation (IN - MP819) EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry for water associated independent laboratory validation (IN - JT333) EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry for water associated independent laboratory validation (IN - MP819) EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry for sediment associated independent laboratory validation (IN - JT333) EF $22,000.00 $7,700.00 98 8 50 .6100 1 158.1300 Environmental chemistry for sediment associated independent laboratory validation (IN - MP819) EF $22,000.00 $7,700.00 98 Totals: $1,484,513.00 $518,980.00 6,590 Paperwork Burden

– Indoxacarb total 1 T he environmental chemistry analytical method s have recently been renumbered to GDLN 850.6100. See: http://www.regulations.gov/#!documentDetail;D=EPA - HQ - OPPT - 2009 - 015 4 - 0008 2 All sediment testing should include quantification of parent indoxacarb, IN - JT333 and IN - MP819 in both pore water and sediment and report results (i.e.., endpoints) in terms of parent indoxacarb, IN - JT333 and IN - MP819. 3 A tiered approach using t oxicity data from sub - chronic (10 - day) sediment toxicity tests with parent indoxacarb and the three species may be used to determine which species should undergo chronic toxicity testing. **II. Pesticide**  **Indoxacarb** Indoxacarb is a broad - spectrum oxadiazine insecticide, which is used in agricultural sites and indoor and outdoor in non - agricultural sites including residential, commercial, institutional and industrial sites. Indoxacarb is registered for use against cat erpillars, beetles, leafhoppers, ants, fire ants, cockroaches, mole crickets, fleas and ticks. The term “indoxacarb” generall y refers to any of several chemical forms of the compound, differentiated b y S - enantiomer to R - enantiomer ratio. There are two de gradates of concern with Indoxacarb, including IN - JT333 and IN - MP819. There is currently one technical registrant and three technical registrations. Indoxacarb was first registered as a pesticide in the U.S. in 2000 . S ince it was registered after 1984, it was not subject to the reregistration requirements of FIFRA. The FWP was signed on (Month/Day

/Year) . All documents relevant to this registration review case can be found in the Indoxacarb docket (EPA - HQ - OPP - 20 13 - 0367) at www.regulations.gov

. **III. Public Comments**  During the 60 - day

public comment period on the Indoxacarb Preliminary Work Plan, which opened on June 26, 2013 and closed on August 26, 2013, the Agency received seven public comments, five of which required responses. Comments were submitted by the following : The Northwest Horticultural Council, the Phy si cians Committee for Responsible Medicine, the California Stormwater Qualit y Association (CASQA), the Central Valley Water Quality

Control Board, and the San Francisco Bay Water Quality

Control Board . The respo nse to these comments is found in the document, Response to Public Comments on the EFED Registration Review Problem Formulation, (Sternberg, Koper, Sankula, November 2013) and BEAD Response to Comments Received During Indoxacarb Registration Review Docket Opening (Kaul, Smearman, Alsadek, November 2013) and are summarized below. The comments do not address the timeline described in the PWP, but they do address the planned ecological

### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb**  and human health risk assessments a nd data requirements. In the PWP, EPA also solicited comments on the specific topics of environmental justice, water quality concerns, and trade irritants, comments and supporting information were received on those issues. This section does not capture e very comment made about the PWP nor all of the Agency ’s responses. Summarized below are public comments that resulted in changes to the anticipated registration review data needs, risk assessments, or timeline, or are of a broader regulatory nature. Publ ic comments and EPA responses in their entirety are located in the docket, EPA - HQ - OPP - 2013 - 0367. Summarized public comments and Agency responses related to the anticipated ecological risk assessment or data needs are in the Response to Public Comment on the EFED Registration Review Problem Formulation for Indoxacarb (D415048) while those relevant to the anticipated economic impacts or data needs are in the BEAD Response to Comments Received During the Indoxacarb Registration Review Docket Opening (Kaul, S mearman, Alsadek, November 18, 2013) . **Comment 1 :**  **Northwest Horticultural Council in EPA -**  **HQ -**  **OPP -**  **2013 -**  **0367.** Indonesia and Saudi Arabia, who are among the top export markets for U.S. apples, do not have a maximum residue limit (MRL) for indoxacarb residues in apples. Saudi Arabia also has no MRL for indoxacarb in pears. Brazil, China and Canada have no MRL on c herries. In addition, Canada has no tolerance for indoxacarb. These countries are top export markets for Northwest growers; therefore, we request that EPA harmonize MRLs for these countries with US tolerances. **EPA Response 1:** During registration revie w, the Agency will work to minimize trade irritants and harmonize US tolerances with MRL s with its trading partners, to the extent feasible (and consistent with domestic law). To facilitate this, the Agency works with the USDA Foreign Agricultural Service and the United States Trade Representative to identify potential trade irritants. EPA is currently working with some of the countries identified b y Northwest Horticultural Council to assist with the development of science - based MRL s. **Comment 2**  **:** We also encourage the use of (Q)SAR data either in place of, or addition to, the fish experimental data. When correctly applied, (Q)SARs can feasibl y replace in vivo data in some instances; the submission of (Q)SAR data in addition to in vivo data would increase Agency and registrant comfort and confidence with the use and evaluation of data from such methods, and so we encourage the regis trant to do so. **EPA Response 2**  **:** (Q)SAR - ty pe data may

be considered in the absence of experimental data at the time of the Registration Review ecological risk assessment. **Comment 3**  **: ASQA**  **, August 26, 2013 :**  Additional study is needed on environmental fate and aquatic toxicity to invertebrates in water and sediment, for parent compound and degradates. CASQA strongly believes that the following additional studies should be included as required studies in both the Work Plan and in Tables 9 - 1 / 9 - 2 of the Problem Formulation to address data gaps:

### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb** 

 Provide environmental fate - related data for the major indoxacarb degradates, I N - JT333 and IN MP819.  Develop chronic toxicity end points for freshwater and marine invertebrates for the major degradates, IN - JT333 and IN - MP819.  Provide both acute and chronic ecological effects studies for aquatic invertebrates in sediment, both for parent indoxacarb and the major degradates, IN - JT333 and IN - MP819. **Comment 4**  **: Central Valley Regional Water Quality Control B**  **oard:** Ecological Risk Assessment Requires Sediment Toxicity Data: Life - cy cle toxicity testing and/or sublethal/chronic toxicity testing in a sediment exposure with a sensitive species (e.g., a chironomid). One data gap that is not proposed to be filled is the effects on benthic organisms in sediment exposures...The Office of Pesticide Programs required toxicity

data from sediment exposures with Hy alella azteca for the registration review of py rethroids, and a sediment exposure toxicity test should also be re quired for indoxacarb. To date, there are very few sublethal or chronic exposure toxicity data for aquatic organisms available for indoxacarb...Of the few available aquatic organism toxicity data for this compound, it appears that chironomids are more sensi tive than amphipods (Ding et al. 2011); thus a life - cy cle toxicity test or a test reporting sublethal endpoints for chironomid sediment exposures should be required in the data call in. **Comment 5**  **: San Francisco Bay Water Quality Control Board:**  OPP shoul d require studies to address ecological effects data gaps, including (1) data on the environmental fate of indoxacarb degradates IN - JT333 and IN - MP819; (2) chronic toxicity end point for freshwater and marine invertebrates for these same degradates; and (3 ) acute and chronic ecological effects studies for aquatic invertebrates in sediment for indoxacarb and its degradates. **EPA Response 3,**  **4, 5**  **:** In regards to requiring studies to generate data on the environmental fate of indoxacarb degradates IN - JT333 and I N - MP819, EFED recommends requesting the following additional environmental fate data for IN - JT333 and IN - MP819 based on toxicity data indicati ng that degradate IN - JT333 is more acutely toxic to freshwater fish and degradate IN - MP819 is more acutely toxic to freshwater invertebrates than parent indoxacarb:

 Guideline 835.2120

– Hy droly sis (TGAI)  Guideline 835.4100

– Aerobic Soil Metabolism (TGAI)  Guideline 835.4300

– Aerobic Aquatic Metabolism (TGAI)  Guideline 835.1230

– Adsorption/Desorption (Batch Equilibrium) (TGAI)  Guideline 835.1240

– Leaching (TGAI)  Guideline 850.6100

– Environmental Chemistry Methods (ECMs) and Associated Independent La boratory

Validations (ILVs) for Soil, Water and Sediment (IN - JT333 and IN MP819) In regards to requiring studies to generate chronic toxicity endpoints for freshwater and marine invertebrates for indoxacarb degradates IN - JT333 and IN - MP819, the problem fo rmulation indicates that, in the absence of these data, chronic toxicity endpoints for freshwater and marine invertebrates will be estimated using available toxicity data for parent indoxacarb and acute toxicity relationships between the degradates and par ent. The Agency considers this to be a conservative approach, and a rationale for

### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb**  why the Agency ’s approach is not reasonable has not been provided. Therefore, the Agency does not recommend requesting chronic toxicity data for freshwater and marine inve rtebrates for IN - JT333 and IN - MP819. The Agency considers the commenter’ s concerns regarding the toxicity of indoxacarb and degradates IN - JT333 and IN - MP819 to sediment - dwelling invertebrates to be valid. In addition, indoxacarb triggers the Part 158 data requirement for (non - guideline) whole sediment, chronic freshwater and m arine invertebrates testing. Therefore, the Agency recommends requesting non - guideline, whole sediment, chronic sediment tests with the midge Chironomus dilutus , freshwater amphipod Hyalella azteca , and estuarine/marine amphipod Leptocheirus plumulosus wi th parent indoxacarb. A tiered approach using toxicity

data from sub - chronic (10 - day ) sediment toxicity tests with parent indoxacarb and the three species may be used to determine which species should undergo chronic toxicity testing. All sediment testin g should include quantification of parent indoxacarb, IN - JT333, and I N - MP819 in both pore water and sediment and report results ( i.e. , endpoints) in term of parent indoxacarb, IN - JT333, and IN - MP819. Consistent with what was proposed in the problem formul ation for the aquatic assessment, The Agency will use the toxic equivalency (TEQ) approach to assess the toxicity of both parent indoxacarb and degradates IN - JT333 and IN - MP819 to sediment - dwelling invertebrates using the results of this testing. **Comment 6**  **: CASQA:**  Require registrants to develop practical environmental chemical anal ys is methods... CASQA appreciates OPP’s acknowledgement in the Problem Formulation (Table 9 - 1) of the need for “Anal yt ical Methods

– Soil and Water”. However, the Problem Formulation should clearly specify that such anal yt ical methods are needed for indoxacarb and its major degradates, IN - JT333 and IN - MP819, in both water and sediment. We further request that EPA develop specifications for this requirement that ensure that the registrant wil l develop practical analy tical methods for indoxacarb and its major degradates in both water and sediment. Although EPA often requires registrants to submit analy tical methods for measurements of pesticides in soil and water, these methods are often not s ufficientl y sensitive for the anal ys is of pesticides at environmentally relevant concentrations for environmentall y relevant matrices, such as ambient waters and sediments, wastewater effluent, and biosolids... Analy tical methods are needed that are practica

ble for use in commercial and government anal yt ical laboratories, and are capable of producing anal yt ical results with sufficiently low detection limits to quantify pesticides at environmentally

relevant levels. Such methods do not exist for many pesticide s; we are not aware of commerciall y available analytical services for indoxacarb. This requirement should be explicitly included in the Work Plan and Table 9 - 1 of the Registration Review Work Plan. Furthermore, as a general practice, the pesticide manufac turer, at the time of initial registration of its product, should be required by EPA to develop such anal yt ical methods, to allow for meaningful environmental monitoring of the impacts of approved pesticides. **Comment 7** 

**: Central Valley Regional Water**  **Quality Control Board :**  Chemical Anal ys is Method Needed: Development of a EPA - approved chemical anal ys is method for both water and sediment matrices. The use of indoxacarb will likely increase in California as it is employ ed as a replacement product for mo re restricted compounds, and as use increases, it will be necessary to monitor for

### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb**  indoxacarb in ambient waters and sediments. A standard chemical anal ys is method for both the parent compound and major degradates is necessary for effective environmental m onitoring. At this time, there are no reported detections of indoxacarb in water in California because no environmental monitoring studies have been conducted, and will not likely occur until there is a standard method available from the US EPA. L ack of a chemical method and monitoring may delay or hinder recognition of potential problems. Because indoxacarb is a h ydrophobic pesticide, it is likely to be found in the sediment and both sediment and aqueous chemical analy sis methods are needed for effectiv e environmental monitoring. **Comment 8**  **: San Francisco Bay Water Quality Control Board:**  OPP should require the registrant to develop practical analy

tical methods for indoxacarb and its major degradates in both water and sediment that obtain detection levels at environmentally relevant concentrations. **EPA Response 6,**  **7, 8**  **:** The Agency concurs with the commenters and submission of data on the environmental chemistry

methods (ECMs) and associated independent laboratory validations (ILVs) is anticipated to be required for indoxacarb and its major degradates for water, soil and sediment. If there is risk concern for a given taxon, ECMs should be available for the environmental media in which organisms of the taxon reside. These ECMs should have limits of q uantitation (L OQ) for the residues of concern that are lower than the relevant toxicological levels of concern. Based on the toxicity profile of indoxacarb, its properties, and results of previous risk assessments, the ECMs for the anal ys is of soil, water and sediment will be required and reviewed by the Agency . **Comment 9**  **: CASQA:**  Require registrants to produce water qualit y monitoring data. OPP has requested submittal of water quality monitoring data for indoxacarb in th e Preliminary Work Plan (p.13). CASQA agrees that monitoring data would be invaluable for registration review. We encourage EPA to require pesticide registrants to provid e environmental monitoring data for products registered for uses in urban areas, and especiall y to require provision o f such data from urban creeks (both water and sediment matrices). OPP has requested submittal of water quality monitoring data for indoxacarb in the Preliminary

Work Plan (p.13). CASQA agrees that monitoring data would be invaluable for registration review . We encourage EPA to require pesticide registrants to provide environmental monitoring data for products registered for uses in urban areas, and especiall y to require provision of such data from urban creeks (both water and sediment matrices). **Comment 10**  **: Central Valley Regional Water Quality Control Board**  **:** Little monitoring data is available for indoxacarb, but one study did report detections in bed sediments of urban streams in central Texas (Hintzen et al. 2009). The detection frequency of indoxacarb of 37.7% was approaching that of some py rethroids (41.2 - 94.1%). The reported sediment concentrations in this study were a mean of 8.0 μ/g OC and a maximum of 69 μ/g OC. The 10 - d sediment L C50 for Chironomus dilutus is 11.3 μ/g OC, indicating that potent ially toxic levels of indoxacarb are already occurring (Ding et al. 2011). This study of urban streams highlights the similarity between indoxacarb and p yrethroids, and how the lessons learned from non - agricultural use of p yr ethroids can be applied to ind oxacarb during this registration review to prevent more widespread problems than potentially alread y exist. This includes modeling urban runoff from outdoor applications to impervious surfaces, and potentially similar restrictions on applications to these ty pes of surfaces as were recently adopted for py

rethroids. L imiting

### Studies Requested in DCIs **for Registration Review Case**  **: Indoxacarb**  applications to crack and crevice and spot treatment instead of band treatments could prevent the next wave of pesticide contamination in urban streams. **EPA Response 9, 10**  : The Agency will use the best available data for the Registration Review risk assessment as indicated in the indoxacarb problem formulation and determine if additional monitoring data are needed on a case - by - case basis.
**I V**  **. Need for and Uses of the Data Generated**  **Study Title: Larval Honey Bee Acute Oral Toxicity (DPX**  **- MP062)**  **Rationale for Requiring the Data** T he available toxicity studies do not address possible affects on brood (larvae and pupae) survival. In doxacarb may be directly sprayed on pollen and/or nectar of treated plants and subsequently brought back to hive where larvae and pupae may be exposed. Because of the potential for pollen and nectar to be contaminated with indoxacarb , and subsequently brought back to the hive, it is import ant to determine the toxicity of this compound to brood. Therefore, a non - guideline honeybee larval toxicity study is needed. The Office of Pesticide Programs has made available interim guidance regarding ecological testing for invertebrates with the hone y bee. These can be found at: http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/ terrestrial_biology_tech_team/honeybee_data_interim_guidance.htm **Practical Utility of the Data How**  **will the data be used?** The 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 risk assessment for beneficial terrestrial invertebrates to determine whether indoxa carb use causes unreasonable adverse effects to these taxa. The effects data will be used to determine the potential for risk to beneficial terrestrial invertebrates thr ough direct effects on larval bees. **How could the data impact the Agency’s future**  **decision -**  **making?** The data EPA intends to call in will inform the determination required under FIFRA or the ESA as to whether continued registr ation of a pesticide is likely to result in unreasonable adverse effect non - target species or is not likely to jeo pardize listed or endangered species or its critical habitat. The lack of these data will limit the flexibility that the Agency and registrants have in coming in to compliance with ESA an d could result in significant use restrictions. In addition, the lac k of these data may result in assumed risk and potential mitigation of indoxacarb formulations under FIFRA.