2 • Guideline 835.1230

– Adso rption/Desorption (Batch Equilibrium) (IN

- JT333 and IN

MP819; TGAI)

• Guideline 835.1240

– Leaching (IN

- JT333 and IN

- MP819; TGAI)

• Guideline 850.6100

– Environmental Chemistry Methods (ECMs) and Associated Independent Laboratory Validations (ILVs) for Soi l, Water and Sediment (IN

- JT333 and IN

- MP819)

• Non

- guideline whole sediment, chronic invertebrates freshwater and marine with Chironomus dilutus

, Hyalella azteca , and Leptocheirus plumulosus (indoxacarb, TGAI): 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 testing 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

- MP819.3 1. Comment from the Northwest Horticultural Council

Comment: “The insecticide indoxacarb is primarily used as a single application, late season treatment for suppression of earwigs in sensitive, high value varieties of apple. This use pattern should have minimal effect on bee populations.”

Response: The Agency ap preciates this clarification of the use pattern of indoxacarb on apple.

2. Comments from the Physicians Committee for Responsible Medicine

Comment: “ We recommend that OECD Test Guideline 223, Avian Acute Oral Toxicity Test, be used as the protocol instead of EPA Guideline 850.2100 in the interest of reducing the numbers of animals used by up to 61% 1 . We also refer the registrant to the “Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Stu dy)” available on the Agency’s website.”

EPA Response: EFED concurs that the “Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study)” 1 should be consulted if the registrant intends to submit an avian acute oral study based on OECD Test Guideline 223. It should be noted that one of the criteria cited in the guidance for classifying a study based on OECD Test Guideline 223 as “acceptable” is that study is conducted using bobwhite quail. The guidance further states that “other test species may be acceptable if they have low background mortality in the laboratory and do not regurgitate during the study; however, if a species other than bobwhite quail is used, the study should be reviewed by the Terrestrial Biology Tech Team (TBTT)

- see below; please note that the background mortality data for the species in question should be available from the submitting laboratory at the time of the TBTT review.”

Comment: “With respect to the acute toxi city for estuarine and marine fish, it appears that some data is available: “Indoxacarb, its R

- enantiomer and degradates are, “moderately to very highly toxic” to freshwater and estuarine/marine fish on an acute basis with LC50s ranging from 0.024 to > 1.3 mg/L.” 2

We also found data that may be of use to meet the freshwater fish toxicity requirement using coldwater species; according to this study, Indoxacarb has an LC50 of 650ppb in rainbow trout. 3 LC50 values are also available for carp and channel catfi sh. 4

If this data is not sufficient then we recommend the registrant conduct an acute threshold or “limit test” which can reduce the number of animals used. This approach was first pioneered on the observation that fish are rarely more sensitive than alg ae and daphnia. 5,6 The fish median

1 http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/review_av ian_acute_oral_oecd_ tg223.htm4 lethal concentration (LC50) test is replaced with an acute threshold test in which fish testing would be performed at one concentration only (the lowest EC50 concentration obtained with previous algae and daphnia testing) . A version of this approach has been adopted by the OECD as a guidance document. 7

In this case since the EC50 in invertebrates is already known and so low, conducting a limit test for fish at this level could accomplish the Agency’s data needs while usin g many fewer fish than a full acute toxicity study, and providing an effective level of protection to wild fish populations.”

Response: The Agency is aware of the cited data for the acute toxicity of indoxacarb to freshwater and estuarine/marine fish. Th is data is among those cited in Table 5

- 1 of the problem formulation. According to OPPTS 850.1075: Fish Acute Toxicity Test, Freshwater and Marine, “Definitive testing may be waived if limit testing with at least 30 organisms shows LC50 levels to be great er than 1,000 mg/L based on 100 percent active ingredients (AI), or the limits of water solubility or dispersibility. For pesticides, a lower level of 100 mg AI/L may be tested when estimated environmental concentrations are not expected to exceed 100 mg/L (ppm) as might occur with pesticide use. Prior to selection of definitive test concentrations it may be advisable to conduct a range

- finding test. Results of any range

- finding and limit tests should be reported with results of the definitive test.”

Comm ent: “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 feasibly replace in vivo data in some instances; the submission of (Q)SAR data in addition to in vivo data wo uld increase Agency and registrant comfort and confidence with the use and evaluation of data from such methods, and so we encourage the registrant to do so.”

Response: (Q)SAR

- type data may be considered in the absence of experimental data at the time of the Registration Review ecological risk assessment.

3. Comments from CASQA, the Central Valley Regional Water Quality Control Board, and the San Francisco Bay Water Quality Control Board

Topic: Assessing risk from urban sources of exposure

CASQA Comment : “Risk Analysis modeling approach must explicityly include urban sources/pathways.

The Work Plan should explicitly address assessment of potential ecological effects from urban runoff sources, including the following elements:

• Develop Conceptual Models : CASQA strongly recommends development of conceptual models of indoxacarb fate and transport, with flow charts illustrating the principal pathways for pesticides to cause effects in the terrestrial and aquatic environments, including explicit depiction of urban runoff pathways to receiving waters. These5 conceptual model diagrams should be used to guide the development of the ecological risk assessment. (See additional information in Modeling Attachment to this letter.)

• Specify Mathematical Modeling Approac h: neither the Problem Formulation nor the Preliminary Work Plan include any reference to modeling of urban runoff; both documents should be revised to incorporate mathematical modeling to address urban rainfall/runoff exposure pathways.

• Separately include “landscaped (pervious)” areas and “impervious” areas as urban source categories in conceptual models and mathematical modeling.

• Account separately for water and sediment matrices in assessments of both exposure and effects for aquatic organisms in concept ual models and mathematical modeling.

• Calculate four

- day rolling averages and number of exceedances of biological criteria (e.g., LC50) every three years in the analysis of the modeling results, and include the four

- day, three

- year exposure estimates when assessing risks to aquatic organisms.”

Central Valley Regional Water Quality Control Board Comment: Urban runoff from outdoor applications to impervious surfaces and turf should be modeled.

San Francisco Bay Water Quality Control Board Comment: The risk assessment must include modeling that fully accounts for urban fate and transport mechanisms, particularly the broad expanses of impervious and highly compacted pervious surfaces; washoff3 following impervious surface applications due to precipit ation and irrigation spray; and direct flow through storm drains to rivers, streams, and bays. OPP has included these elements in its registration review for bifenthrin. Please see the Registration Review Problem Formulation for Bifenthrin (Docket ID Numbe r EPA

– HQ

– OPP

– 2010

– 0384).

Response: In the problem formulation section of the preliminary draft of the Registration Review ecological risk assessment for indoxacarb, EFED will revise the risk exposure pathways of concern to include relevant urban sources of exposure to indoxacarb including droplets, drift, and deposition on impervious surfaces.

EFED acknowledges the need for an improved urban runoff scenario. However, at the present time, EFED considers the use of the impervious scenario (a PRZM modeli ng scenario) as the most suitable available modeling approach for impervious runoff. The PRZM impervious scenario may be used in the tier 2 coupled aquatic models PRZM/EXAMS along with a residential or other suitable scenario such as rights

- of

- way (ROW) t o obtain EECs. The conceptual model for the residential scenario integrates simultaneous modeling of the individual use scenario with an impervious scenario. This approach assumes that no watershed is completely covered by either the 1⁄4 acre lot (the basi s for the residential scenario) or undeveloped land (the basis for the ROW scenario) for residential and ROW use patterns; therefore, differential amounts of runoff will occur within the watershed. The impervious scenario was developed to represent the pa ved areas within a watershed not including roads, parking lots, sidewalks, and buildings outside the 1⁄4 acre lot (the 1⁄4 acre lot scenario accounts for impervious surfaces such as buildings within the represented area). By modeling a separate scenario for i mpervious surfaces, it is also possible to estimate that amount of exposure that could occur when the pesticide is oversprayed onto this surface. Using two scenarios in tandem requires post

- processing of the modeled output in order to derive a weighted EE C that represents6 the contribution of both the pervious ( i.e. , residential and ROW scenarios) and the impervious surfaces. Exposure from both scenarios can also be weighted and aggregated. The daily time series from each model run should be copied from t he times series file (NAME_TS.out) generated from the PRZM graphical user interface (PE5.pl) into the spreadsheet provided. The time series data are then weighted based on percentage of impervious surface, the percentage of the pervious surface treated, a nd an adjusted time series is created. Rolling averages for the relevant durations of exposure (e.g., 21 day and 60 day averages) are calculated, and the relevant

one

- in

- ten year return EEC is generated from these distributions.

The Agency intends to use available non

- agricultural use and usage data, such as the Kline database, the California Department of Pesticide Regulation’s (CDPR) Pesticide Use Reporting Data and Pest Control Operator’s usage survey, and the Residential Joint Venture Task Force homeo wner survey data, to make certain reasonable assumptions regarding various applications and information related to urban/residential use. Due to the limited data available, exposure to the environment and uncertainties will be characterized. Detailed inf ormation on non

agricultural use and usage of indoxacarb would be useful to reduce those uncertainties for the Registration Review ecological risk assessment for indoxacarb.

Topic: Environmental fate and ecological effects data gaps

CASQA Comment: 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:

• Provide environmental fate

- related data for the major indoxacarb degradates, IN

- JT333 and IN

- MP819.

• Develop chronic toxicity end points for freshwater and marine invert ebrates 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.

Sediment toxicity testing should be performed with spiked sediments, rather than by adding the test chemicals to the overlying water. This provides a much more accurate assessment of actual toxicity to benthic organisms. The sediment studies also should include Chironomus dilutus

, as Ding et al. (2010) found this species to be much more sensitive to indoxacarb than Hyalella
azteca , an amphipod commonly used in sediment toxicity testing.”

Central Valley Regional Water Quality Control Board Comment: Ecological Risk Assessment Requir es Sediment Toxicity Data: Life

- cycle toxicity testing and/or sublethal/chronic toxicity testing in a sediment exposure with a sensitive species ( e.g. , a chironomid)7 “One data gap that is not proposed to be filled is the effects on benthic organisms in sediment exposures. lndoxacarb has low water solubility and a high octanol

- water partition coefficient (log Kow=4.65), and it is likely that it will partition to sedime nts once it enters a waterway. The Office of Pesticide Programs required toxicity data from sediment exposures with Hyalella
azteca for the registration review of pyrethroids, and a sediment exposure toxicity test should also be required for indoxacarb. To date, there are very few sublethal or chronic exposure toxicity data for aquatic organisms available for indoxacarb. One study on stream macroinvertebrates reported that indoxacarb exposure can induce downstream drift at concentrations as low as one

- t enth of the LC50 (Beketov and Liess 2008). Of the few available aquatic organism toxicity data for this compound, it appears that chironomids are more sensitive than amphipods (Ding et al. 2011); thus a life

- cycle toxicity test or a test reporting subleth al endpoints for chironomid sediment exposures should be required in the data call in.”

San Francisco Bay Water Quality Control Board Comment: OPP should 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.

Response: In regards to requiring studies to generate data on the environmental fate of indoxacarb degradates IN

- JT333 and IN

- MP819, EFED recommends requesting the following additional environmental fate data for IN

- JT333 and IN

- MP819 ba sed on toxicity data indicating 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

– Hydrolysis (TGAI)

• Guideline 835.4100

– A erobic 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 Laboratory 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 formulation 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 b etween the degradates and parent. EFED considers this to be a conservative approach, and a rationale for why EFED’s approach is not reasonable has not been provided. Therefore, EFED does not recommend requesting chronic toxicity data for freshwater and m arine invertebrates for IN

- JT333 and IN

- MP819.

EFED considers the commenters’ 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 15 8 data requirement for (non

- guideline) whole sediment, chronic freshwater8 and marine invertebrates testing. Therefore, EFED recommends requesting non

- guideline, whole sediment, chronic sediment tests with the midge Chironomus dilutus , freshwater amphipod Hyalella azteca , and estuarine/marine amphipod Leptocheirus plumulosus with 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 wh ich species should undergo chronic toxicity testing. 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 term of parent indoxacarb, IN

- JT33 3, and IN

- MP819. Consistent with what was proposed in the problem formulation for the aquatic assessment, EFED 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.

Topic: Environmental chemical analysis methods

CASQA Comment: Require registrants to develop practical environmental chemical analysis methods

“CASQA appreciates OPP’s acknowledgement in the Problem Formulation (Table 9

- 1) of the need for “Analytical Methods

– Soil and Water”. However, the Problem Formulation should clearly specify that such analytical methods are needed for indoxacarb and its ma jor 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 will develop practical analytical methods for indoxacarb and its major degradates in both water and sediment. Although EPA often requires registrants to submit analytical methods for measurements of pesticides in soil and water, these methods are often not sufficiently sensitive for the analysis of pesticides at environmentally relevant c oncentrations for environmentally relevant matrices, such as ambient waters and sediments, wastewater effluent, and biosolids... Analytical methods are needed that are practicable for use in commercial and government analytical laboratories, and are capable of producing analytical results with sufficiently low detection limits to quantify pesticides at environmentally relevant levels. Such methods do not exist for many pesticides; we are not aware of commercially 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 manufacturer, at the time of initial registration of its product, should be required by E PA to develop such analytical methods, to allow for meaningful environmental monitoring of the impacts of approved pesticides.”

Central Valley Regional Water Quality Control Board Comment: Chemical Analysis Method Needed: Development of a EPA

- approved che mical analysis method for both water and sediment matrices9 “The use of indoxacarb will likely increase in California as it is employed as a replacement product for more restricted compounds, and as use increases, it will be necessary to monitor for indoxa carb in ambient waters and sediments. A standard chemical analysis method for both the parent compound and major degradates is necessary for effective environmental monitoring. At this time, there are no reported detections of indoxacarb in water in Cali fornia because no environmental monitoring studies have been conducted, and will not likely occur until there is a standard method available from the US EPA. Lack of a chemical method and monitoring may delay or hinder recognition of potential problems. Because indoxacarb is a hydrophobic pesticide, it is likely to be found in the sediment and both sediment and aqueous chemical analysis methods are needed for effective environmental monitoring.”

San Francisco Bay Water Quality Control Board Comment: “ OPP should require the registrant to develop practical analytical methods for indoxacarb and its major degradates in both water and sediment that obtain detection levels at environmentally relevant concentrations. ”

Response: 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 quantitation (LOQ) for the residues of concern that are lower than the rel evant toxicological levels of concern. Based on the toxicity profile of indoxacarb, its properties, and results of previous risk assessments, the ECMs for the analysis of soil, water and sediment will be required and reviewed by the Agency.

Topic: Wate r monitoring data

CASQA Comment: Require registrants to produce water quality monitoring data

“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 inv aluable for registration review. We encourage EPA to require pesticide registrants to provide environmental monitoring data for products registered for uses in urban areas, and especially
to require provision of such data from urban creeks (both water and sediment matrices).”

Central Valley Regional Water Quality Control Board Comment: “ Little monitoring data is available for indoxacarb, but one study did report detections in bed sediments o f urban streams in central Texas (Hintzen et al. 2009). The detection frequency of indoxacarb of 37.7% was approaching that of some pyrethroids (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 LC50 for Chironomus dilutus is 11.3 μ/g OC, indicating that potentially toxic levels of indoxacarb are already occurring (Ding et al. 2011). This study of urban streams highlights the similarity between indoxacarb and pyrethroi ds, and how the lessons learned from non

- agricultural use of pyrethroids can be applied to indoxacarb during this registration review to prevent more widespread problems than potentially already exist. This includes modeling urban runoff from10 outdoor appl ications to impervious surfaces, and potentially similar restrictions on applications to these types of surfaces as were recently adopted for pyrethroids. Limiting applications to crack and crevice and spot treatment instead of band treatments could preve nt the next wave of pesticide contamination in urban streams.”

Response: 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.

Topic: Consideration of California

- specific data/scenarios

Central Valley Regional Water Quality Control Board Comment: “ The Preliminary Work Plan (p. 6) reports an average of 39,000 pounds a.i. indoxacarb for 558,0 00 treated acres from 2007

- 2011; based on the PUR data, it appears that use in California makes up the majority of agricultural use nationwide. If this is true, then ecological risk assessment should specifically assess California conditions, crops, and a quatic life and wildlife, particularly in the intensive agricultural areas of California where toxicity in waterways has already been documented by
current

- use pesticides, such as the Central Coast and Central Valley.”

Response: In the case of a nation

- wi de risk assessment conducted under Registration Review, the action area will encompass the entire U.S. and its territories.

Topic: Use of most sensitive species

San Francisco Bay Water Quality Control Board Comment: “ The modeling must account for aquati c organism exposures in both water and sediment matrices, using the most sensitive species. For sediment exposures, Chironomus dilutu s is more sensitive to indoxacarb than Hyalella azteca

. ”

Response: As stated above, EFED recommends requesting non

- guideline, whole sediment, chronic sediment tests with Chironomus dilutus

, Hyalella azteca , and Leptocheirus plumulosus with 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.