UNITED STATES E NV I RONME NT AL P ROTECTION AGENCY WASHINGTON D.C., 20460

PC Co d e: I 13202 DP Ba r co d e: 427946

Da t e: Jul y 22, 20 1 5 MEMO R AN D UM SU B JECT:

FR O M:

T HRO UG H:

T O : Response to Public Comments on the Famoxadone Regi stration Review Problem Fo rmulati on F

r eeborn G. Jewett , Biologist 

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# ~ Christop h er M. Koper , M.S. ,

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# 0u~ 2.o •c; Env ironm ental Risk Branch I 

### U Environm e ntal Fa t e and Effects Division (7507P

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### j) Office of Pesticide Program s 

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# tJ**~ ~\~,_1,<**  Gregory Orrick , Ph.D. , RAPL**~ ~** **~** Sujatha Sankula, Ph.D ., Branch Chief • ....._ · Environmental Risk B ra n ch I Env ironm ental f-ate and Effects Division (7507 P ) Office of Pe s ticide Program s Chr i s tin a Sche lt ema, Che mi ca l Review Manager Avivah Jakob , Team Leader Kell y Sherman , Branch C hief Risk Management a nd Impl e mentation Branch 3 Pesticide Re- E valuation Division (7508P)
In respon se to the ' · Re g i strat i on Revi ew: Problem Formulation for the Env ironment a l Fate , Ecological Ri sk, Endangered Species , and Drinking Water Assessments for Famoxadone" ( D423285 ), DuPont Crop Pr o tection submitted co mment s on the "Anticipa t ed Data Needs for th e Famoxadone R egis trati on Review. " The purpose of this memorandum is to address these comments a nd data submissions. C omm e nt s fr om D uPo n t C r o p Pr o t ect i o n: Co mm e n t: " GDL 835.4 300

- Aerobic aqua ti c metaboli s m: DuPont belie ves the two systems selec t ed do meet the r equest of EPA OPPTS 835.4300 guidelines on sedimen t se l ectio n: • OC co ntents : EPA OPPTS 835.4300 (low OC o/o : 0.5-2.5 ; high OC%: 2.5-7 .5) ; DuP o nt s tud y (A MR 3662-95 , MRID 44946405) ( l ow OC%: 1.17 or OM % : 2.0 1 ; high QC % : 2.62 or OM % : 4.51 ). It clearly indicates QC content s at both low and hi g h levels are within the range s ug ges ted b y EPA guidel ines

. Texture difference: the guidelines of EPA OPPTS 835.4300 state that the difference in

[clay+silt] co ntent for the two sediments should normally be at least 20%. In DuPont study (ARM 3662

- 95, MRID 44946405), the difference between the coarse texture and fine texture is equal to 72.4%

- 51.2% =21.2%, which does meet the guideline requirement of at least 20%

.  Therefore, DuPont believes the study ARM 3662

- 95, MRID 44946405, provided to EPA, does meet current study guideline and an additional system test is not necessary. EPA Response: The Agency agrees that an additional test system is not necessary. The ti tle of DuPont study AMR 3662

- 95 suggests that a single sediment: water system was tested. The organic carbon contents and texture differences of selected sediments meet the guideline requirements. Comment: “ GDLN 860.1380

– Storage Stability in Soil and W ater: There is a GLP frozen storage stability study for soil, AMR 3096

- 94, MRID 44302453. It concludes that residues are stable for up to 18 months when stored frozen. Water storage stability is not necessary because our sample analysis standard practice s tates that once the samples are extracted, the samples are immediately analyzed. ” EPA Response: The Agency appreciates the reference for the storage stability study in soil. Since there are no aquatic uses for famoxadone, a storage stability in water is not warranted at this time. The Agency interprets the immediate analysis for aqueous samples is applicable to laboratory studies. Comment: “ NON

- GDLN

– Pollinator Tier II Semi

- field Toxicity Testing (tunnel/enclosure studies). The criteria for conductin g this test are dependent on the results from the acute and chronic laboratory tests. Therefore, this test should be conditionally required based on the results from the laboratory tests. If the risk assessment results in low risk, then the studies should no longer be required. NON

- GDLN

– Pollinator Tier II Semi

- field Toxicity Testing (feeding studies): The criteria for conducting this test are dependent on the results from the acute and chronic laboratory tests. Therefore, this test should be conditionall y required based on the results from the laboratory tests. If the risk assessment results in low risk, then the studies should no longer be required. EPA Response: The Agency agrees that these tests are conditionally required based on the results of the T ier I pollinator studies. Comment: “ NON

- GDLN

– Pollinator Acute Oral Toxicity, Adult: This study has been conducted and the final report has been issued: AMR

- 5165

- 98 .” EPA response: The Agency appreciates the timely submission and will conduct a full review of the study once it is received. When the DER is completed, the Registrant will receive notification and a copy.Comment: “ NON

- GDLN

– Pollinator Acute Oral Toxicity, Larvae DuPont Response: This

study has been conducted and th e final report has been issued: DuPont

- 40437.” EPA response: The Agency appreciates the timely submission and will conduct a full review of the study once it is received. When the DER is completed, the Registrant will receive notification and a copy. Com ment: NON

- GDLN

– Pollinator Chronic Oral Toxicity, Adult : This study is in progress (DuPont

- 40438) and will be completed in accordance with the time specifications in the proposed work plan. EPA response: The Agency will conduct a full review of the study once it is received. When the DER is completed, the Registrant will receive notification and a copy. Comment : NON

- GDLN

– Pollinato r Chronic Oral Toxicity, Larvae: There is currently no standardized method for this test that is currently being successfull y conducted. While a study design has be en proposed, it is currently undergoi ng development and ring testing and is not currently ready for regulatory te sting. The larval oral toxicity study that DuPont has conducted (D uPont

- 40437) actually dosed the larva e for three consecutive days instead of one, with no effect. Because there is no standardized method for this te st, DuPont recommends that this study should be considered for both data points. EPA response: The Agency welcomes the submission of the DuPont study 40437 and will conduct a full review of the study once it is received. As with all data submitted to the Agency, the reviewer will determine whether the study is scientifically sound and can be used to fulfil guideline requirements

. Chronic larvae studies need to be conducted with multiple doses and larvae need to be monitored until pupae emergence. A study with a single three - day dosage may potentially fulfil the acute honeybee larvae toxicity guideline requirement, but not the chron ic guideline. T he registrant is required to submit a protocol for approval prior to initiating the study until such time as the OCSPP 850 Pollinator Larvae Chronic Oral Toxicity testing guidelines are published. Draft guidance is available: http://www.oecd.org/chemicalsafety/testing/Draft_GD_honeybee_larval_tox_repeated_e xposure_25_February_2014.pdf Comment : NON

- GDLN

– Whole Sedim ent: Chronic Invertebrates Freshwater and Marine (using Chironomus dilutes , Hyalella azteca and/or Leptocheirus plumulosus ): What is being request ed needs further clarification. A chronic sediment test with the freshwater organism C. riparius is already being conducted. This study i s being conducted in accordance with an OECD test guideline (OECD 2 18) and modifications that were required by EPA when designing this test . EPA indicated that this study (OECD 218 with modifications) would s uffice the need for the benthic invertebrate study. Therefore, this study i s not needed since an EPA agreed sedimentstudy is in progress (s ee below) that will produce the relevant and necessary data to conduct a

sediment risk assessment.
 It needs to be fu rther clarified if another sediment test with a freshwater organism is requested as part of the proposed work plan.
 DuPont agrees with the proposal to conduct the marine chronic sediment toxicity test. EPA response: Based on the fate properties of famoxad one, 3 chronic whole sediment toxicity tests are required as outlined in 40 CFR Part 158 Subpart G (USEPA 2007) 1

. The chronic freshwater sediment toxicity tests must be conducted on one amphipod and one midge species. The study currently being conducted by the registrant using the midge Chironomus riparius should be submitted to the Agency for review. If this study is determined to be scientifically sound, it will be used to fulfill guideline requirements for a chronic whole sediment toxicity test with a mi dge species. The midge and amphipod have different life histories, occupy different taxonomic groups (amphipods are crustaceans, while midges are insects) and generally interact with sediments in different ways. Chironomid larvae are more infaunal (subme rged in the sediment) whereas amphipods are more epibenthic (moving in and out of the surficial sediment layer). As a result, the amphipod and midge may experience differences in chemical uptake relative to different exposure routes (pore water respiration , sediment ingestion, food ingestion, dermal uptake, respiration of overlying water). Furthermore, physiological and taxonomic differences between midges (Class: Insecta; Order: Diptera) and amphipods (Class: Malacostraca; Order: Amphipoda) may result in s ubstantial sensitivity differences between these taxa, especially with the highly

- specific modes of action of many pesticides. Therefore, a chronic whole sediment toxicity test is being requested using the amphipod species Hyalella azteca. As indicated in 40 CFR Part 158, the registrant is required to submit a protocol for approval prior to initiating the study until such time as the OCSPP 850 chronic sediment testing guidelines are published. The Registrant is welcome to submit a formal Waiver Request if t hey feel the requirement should be waived if there is sufficient evidence of low toxicity. In addition , a chronic estuarine/marine sediment toxicity test is requested using the amphipod species Leptocheirus plumulosus. As indicated in 40 CFR Part 158, the registrant is required to submit a protocol for approval prior to initiating the study until such time as the OCSPP 850 chronic sediment testing guidelines are published. Comment ; GDLN 850.1010

– Acute Toxicity, freshwat er invertebrates ( Daphnia magna )

– (IN

- KZ007, IN

- MN467, IN

- MN968, IN

- M N

- 468

- 0, IN

- KF015 and IN

- H3310): Acute daphnid tests h ave been conducted with INKZ007 (DuPont

- 31078), IN

- MN467 (DuPont

- 31080), IN

MN468 (HLR

- 848

- 96 [MRID 49502702], DuPon t

- 29778), IN

- KF0 15 (AMR 3978

- 96 [MRID 49502704], DuPont

- 31082), and IN

- H3310 (HLR 380

- 96 [MRID 49502703], DuPont

- 29777). An acute daphnid test has not been conducted with IN

- MN968. However, it is DuPont’ s position

1 Specific language available in the preamble to 40 CFR Part 158 (p. 60944) : U.S. Environmental Protection Agency. 2007. Pesticides; Data Requirements for Conventional Chemicals, Technical Amendments, and Data Requirements for Biochemical and Microbial Pest icides; Final Rules Federal Register / Vol. 72, No. 207 / Friday, October 26, 2007.that this study is not needed based on str uctural similari ty with another famoxadone metabolite

(IN

- JL856) for which studies were conducted (HLR 382

- 96 [MRID 49502701], DuPont

- 31079).
 This similarity can be further confirm ed based on results from ECOSAR (v1.11). The results for acute daphnid toxi city range from 0 .676 to 43.595 mg/L. The lowest EC50 can be consid ered less toxic than famoxadone and of similar toxicity to IN

- JL856 (EC50 = 0.190 to 9.6 mg/L). Therefore, it is DuPont’s position that an acute daphnid test with IN

- MN968 is not needed. EPA response: As indicated in the Problem Formulation, it is the opinion of the Agency that the ECOSAR results for famoxadone are not applicable for use in assessing the toxici ty of the degradates because the ECOSAR

- predicted and empirically

- derived toxicity values for the parent chemical, famoxadone, are not closely aligned and cannot be calibrated for accuracy. Furthermore, the Agency does not consider the structural similarity of the degradates IN

- MN968 and IN

- JL856 sufficient evidence to assume equal toxicity, as IN

- MN968 contains unique functional groups that could potentially affect reactivity

. Nevertheless, the Agency would welcome a formal waiver request if DuPont could provide additional evidence to indicate that the degradates IN

- MN968 and IN

- JL856 are toxico logically similar

. Until data characterizing the toxicity of IN

- MN968 are submitted, the Agency will assume equal toxicity with the most toxic degradate.