Page 2 of 26 The problem formulation is intended to provide an overview of what is currently known regarding the environmental fate and ecological effects associated with fluridone and its degradates and outlines uncertainties regardi ng attributes of the parent compound and its transformation products. It describes the pr eliminary ecological ri sk hypothesis and the processes that will be used during the completion of drinki ng water and ecological risk assessments in support of registration. This document also recommends studies that should be included in a data call-in (DC I) to address uncertainties surr ounding potential ecolo gical effects (DP Barcode D362249) of fluridone.

In addition to the changes in response to co mments, EFED has corrected some typographical errors and EFED has updated the summary tables of ecological effects data based on reviews completed for MRID 00103297 acute toxicity to daphnia, MRID 00103297 acute toxicity to fish studies, MRID 45915601 early life stage study on Chinook salmon, and MRID 0046112001 acute toxicity of fluridone to Chinook salmon since the Preliminary Problem formulation was completed.



## Response to Comments

A. Comments from Dan Hillard rep resenting Withlacoochee Area Residents, Inc. (EPA-HQ-OPP-2009-0160-008)

1. Comment: Page 3, Section 3.2 states “We suggest in the strongest terms that such evaluation reasonably includes es tuarine environments, indigenous listed and unlisted species and habitat. Evaluations of the pesticide in such environments should be of sufficiently broad scope to provide substantive understa nding of potential impacts to the collective estuarine ecosystem.”

EFED Response: Consistent with the methods discussed in the problem formulation document, potential risks to non-listed a nd listed species will be consid ered in the ecological risk assessment. This will include potential for risk to estuarine/marine organisms.

2. Comment: Page 3, Section 3.3 states “It is stated that fluridone has low potential for

bioaccumulation in fish. What bioaccumulati on occurs in mammals, mollusks, invertebrates and other marine organisms?

The point of application in the subject complaint was Lake Rou sseau, a lake with substantial surface vegetation cover and naturally shaded at de pth due to high tanin content in the water. The Lower Withlacoochee River is largely shad ed by shoreline trees. Such circumstances interfere with photolysis and associated degradation and ar e not thought unique to this system. It is not clear such considerati ons have been fully evaluated by previous registrations processes or regulat ed by label restrictions. Su ch circumstances may reasonably be concluded to interfere with degradation of the active ingredient and transmit great impact far downstream of the application point.”

EFED Response: One purpose of a Bioconcentration study is to determine if pesticide residues accumulate in fish used as human food sources, a nd to determine the extent of pesticide residuesPage 3 of 26 in edible portions of such fish. At this tier, if the pesticide has a low octanol/water partition coefficient, the agency determines that the pesticide has a low potential for bioaccumulation in

fish. Based on the low octanol-wat er partition coefficient (log K OW =1.87), fluridone has a low potential to bioconcentrate and bioaccumulate in terrestrial organisms such as mammals, mollusks, invertebrates, and other marine organisms.

EFED acknowledged in its previous assessmen ts (Registration Review: Preliminary

Problem Formulation for Ecol ogical Risk, Environmental Fa te, and Endangered Species Assessment for Fluridone, dated August 20, 2009 , p. 12) the impact of such factors as depth of water and cloud cover on degr ee of pesticide photolysis in water.

3. Comment: Page 3, Section 3.3.1.a states “It is not clear Fluridone has been evaluated for degradation in sea water or mi xed seawater and fresh water.”

EFED Response: EFED agrees to assess degradation in sea water or mixed seawater and

freshwater.

4. Comment: Page 3, Section 3.3.1.a states “It is no t clear that evaluation of carcinogenic degradates has been evaluated in context of estuarine species or listed species...There is a petition before the Department of Interior and US FWS to revise critical habitat for the West Indian Manatee, which is resi dent to the water bodies disc ussed in this document. The petition will, if adopted, designate these water bodies in whole or part as critical habitat for

the Manatee.”

EFED Response: Potential risk to estuarine/marine organisms is considered in all EFED risk assessments, including potential exposure to de gradates. Page 20 of the Problem Formulation indicates this when it states, “For uses in co astal areas, aquatic habita t also includes marine ecosystems, including estuaries.”

5. Comment: Page 3, Section 3.3.1.e states “The active ingredient should be proscribed from impaired or potentially impaired waters until determination of TMDL is made. The Lower River is so described by the State of Florida. Such evaluation should consider impairment of the water body in context of cumulative impacts (Exhibit G) to include DO, metals, nitrates and other pollutants.”

EFED Response: EFED will evaluate in the risk assessment the potential for the use of fluridone to impair water bodi es. Total Maximum Daily Loads (TMDLs) are established under Section 303(d) of the Clean Water Act and are outside the scope of registering pesticides. If a TMDL is established, EFED will consider how that will need to be reflected on labels.

6. Comment: Page 3, Section 4.0 states “It is requested this review include studies of estuarine species representative of the food chain structur e in general and specific to the West Indian Manatee, sturgeon, sea turtles and sharks.”

EFED Response: Potential risk to estuarine/marine organisms is considered in all EFED risk

assessments.Page 4 of 26 7. Comment: Page 3, Section 4.1 states “Evaluation of toxicity to aquatic and marine organisms appears warranted, both in regards to LD and lesser eff ects. As mentioned previously, the active ingredient appears to have had greatly higher toxicity than expected in tidewaters based on application rates. There is no data related to estuarine environments”

EFED Response: Potential risk to estuarine/marine organisms is considered in all EFED risk

assessments. Data on the estuarine/marine verteb rates and invertebrates are available to assess

risk to estuarine/marine or ganisms (see MRID 00108837, 00112789, and 00103312).

8. Comment: Page 4, Section 4.4 states “The Bureau of Invasive Plant Management in Florida is now assigned to the Fish and Wildlife C onservation Commission (FWCC) effective July 2008. The FWCC is proscribed by state statut e from engaging in any activity related to water quality analysis or enforcement. FWCC do es not perform toxicological screens of fish or other aquatic organisms during die off events . We find this circum stance disconcerting to say the least, and question the state’s oversight process in aq uatic and terrestrial pesticide programs.”

EFED Response: This comment is beyond the scope of the problem formulation for ecological risk assessment performed for registration review.

9. Comment: Page 4, Section 4.4 states “In short, ther e is no basis for defending application of the subject pesticide in tidewater or brack ish water and there are serious doubts that application level limits prescribed by EPA are adequate to address the ecologies of estuarine

environments or direct and i ndirect impacts to listed specie s. We do not see a practical difference between point of “application” vers us “introduction in riverine systems and

downstream estuaries”

EFED Response: As stated on Page 6 of the Problem Formulation, “Fluridone is prohibited from application in tidewater or brackish water; however, as it may be applied in freshwater streams and rivers it could easily enter the estuarine/marine environment.” Risk to estuarine/marine organisms will be evaluated in the risk assessment.



### B. Comments from Kerley Trading, In c., a registrant of fluridone (EPA-HQ-OPP-0160-0026)

1. Comment: Page 2, Comment 1a states “Flurid one Summary Document (EPA-HQ-OPP2009-0160-0002), page 5: Data appear to be re quired to be submitted for fluridone for guideline 850.1400, freshwater fish early life stage. However, no justification was provided for the requirement of this study. Indeed, on page 34 of the Preliminary Problem Document (EPA-HQ-OPP-2009-0160-0003), it stat es that although data are n eeded, “this data will be available from the fish full life cycle.” As such, KTI believes the listing of this data requirement is in error and should not be promul gated to the Final Work Plan and subsequent

Data Call-In.”

EFED Response: The fish early-life stage study fo r freshwater organisms (850.1400) is recommended for all outdoor end-use products for a species that also has acute data (40 CFR Part 158.630, see footnote 1 and 13 of Terrestri al and Aquatic Nontar get organism DataPage 5 of 26 Requirements Table). The reason that data are neededfor the same species is so that an acute-tochronic ratio may be calculated a nd used to estimate chronic toxici ty endpoints to more sensitive species. Acute-to-chronic ratios may be calculated using either da ta from a fish early life stage study or a fish full life cycle study. An acceptable fi sh full-life cycle study is available for the fathead minnow (MRID 00103309). Also, acute da ta on the EP for the Fathead minnow were reviewed since the completion of the problem formulation and found to be acceptable. A study on the TGAI is preferred; however, data for Rain bow trout and Channel catfish indicate that the EP tested did not influence the toxicity of flur idone. In the absence of an acute study on the TGAI, the 96-hr LC 50 for the EP for the Fathead minnow wo uld be used to estimate an ACR.

The estimated ACR is 17.3 based on a 96-hr LC 50 of 8.3 mg a.i./L for the EP (MRID 00103297). Additionally, the weight of evidence does not indicat e a need for additional chronic data on fish. Both the Chinook salmon early life stage study (MRID 45915601) and Fathead minnow full-life cycle study (MRID 00103309) have similar No-Obs ervable-Adverse-Effects-Concentrations (NOAECs). Based on the weight of evidence, EFED is not recommending that an early-life stage study (OPPTS Guideline 850.1400) or full life-cycle study (OPPTS Guideline 850.1500) be requested for a species with acute data at th is time. The problem formulation was updated to reflect this on Pages 16, 32, 35, 36, 38, and 54.

2. Comment: Page 2, Comment 1b states “Fluridone Summary Document (EPA

‐ HQ

‐ OPP

‐ 2009

‐ 0160

‐ 0002), page 5: Data appear to be required to be submitted for fluridone for guideline, 850.1500, fres hwater fish life cycle. KTI requests that this guideline requirement be Reserved. Acceptable fish life cycle data are available with fathead minnow under MRID 00103309 (see page 65 of the Prelim inary Problem Document). KTI recognizes that a full fish life cycle study is required for one species that has acute toxicity data. KTI (with the support of SePro) wi ll either demonstrate that existing fathead minnow acute toxicity data are accepta ble or will generate acceptable acute toxicity data rendering this data requirement moot. Therefore, the requirement for the submission of freshwater fish life cycle

data should be Reserved.”

EFED Response: Based on the weight of evidence, EFED is not recommending that an earlylife stage study (OPPTS Guid eline 850.1400) or full life-cy cle study (OPPTS Guideline 850.1500) be requested for a species with acute data at this time. The problem formulation was updated to reflect this on Pages 16, 32, 35, 36, 38, and 54. See the response to the previous comment 2 for a full explanation.

3. Comment: Page 2-3, Comment 1c states “Fluridone Summary Document (EPA

‐ HQ

‐ OPP

‐ 2009

‐ 0160

‐ 0002), page 5: Data appear to be required to be submitted for fluridone for guideline, 8 50.1300, aquatic invertebrate lif e cycle: daphnid for TGAI; however, on page 31 of the Preliminary Problem Document, data appear to be required for

both TGAI and TEP. KTI believes that data are required fo r TGAI only for the following

reasons: TGAI is listed under 40 CFR Part 158 as the test substance and pages 55 and 56 of the Preliminary Problem Document do not specify th e test material but it is implied that data on the TGAI, not TEP, would be required. KTI re quests that the Agency confirm that data on TGAI only are required for aquatic in vertebrate life cycle: daphnid.”Page 6 of 26 EFED Response: Data on the TEP are not required for OPPTS Guideline 850.1300. This typo is corrected in the revised problem formulation.

4. Comment: Page 3, Comment 1f states, “Prelimin ary Problem Formulation for Ecological Risk, Environmental Fate, and Endangered Species Assessment for Fluridone Summary Document (EPA

‐ HQ

‐ OPP

‐ 2009

‐ 0160

‐ 0003), page 10: Table 3

‐ 3 indicates that there are no monitoring data for fluridone and NMF. There are several publications in which fluridone

levels in water after treatment are monitored ove r time. None of these studies ever detected

residues of NMF.”

EFED Response: EFED asks the registrant to submit a ny publications in which fluridone and Nmethyl formamide (NMF) levels in water after treat ment are monitored over time. Note that the limit of quantitation should be low enough to de tect the concentration of NMF at expected concentrations. If the LOQ and limit of detectio n (LOD) are too high to de tect NMF at relevant concentrations, a monitoring study has no value in predicting whether NMF is expected to occur

in the natural environment. EFED believes that useful pesticide monitoring data should carefully consider spatial and temporal as pects of pesticide transport wh en determining where and when samples are collected. Additionally, monitoring should be conducted from use-specific sites relevant to the pesticide regist ration. Finally, the analytical sa mpling methods used should be appropriate for detecting both fluridone and NMF in samples at an appropriate limit of quantitation.

5. Comment: Page 3, Comment 2a states in regards to the request for data on Aquatic Plant Growth (OPPTS 850.4400 and 850.5400), “ This study/data require ment tests materials against several forms of algae and duckweed ( Lemna gibba ). Fluridone, as an aquatic herbicide, controls duckweed at concentrations below 90 ppb. The label for fluridone lists aquatic plants that are controlle d, partially controlled or not cont rolled. The results of testing fluridone in this study against duckweed can be predicted: fluridone will kill Lemna as it is supposed to do. The other species that are included in this aquatic plant growth study are algae or diatoms. The WhiteCa p label specifies that fluri done does not control algae or diatoms ( Chara, Nitella , and singlecellular, colonial and filamentous species). KTI is not aware of any algae or diatoms that are endange red or threatened species and results from testing fluridone against such organisms would not yield data that woul d be useful in risk assessments or mitigation strategies.”

EFED Response: Tier II Aquatic Plant growth (algal and aquatic vascul ar plant toxicity)

OPPTS Guideline 850.4400 and 850.5400 are recomme nded for all known phytotoxicants (see 40 CFR Part 158.660 Table - Nontarget Plant Prot ection Data Requirements and Footnote 4). EFED understands that fluridone is expected to ha ve effects on vascular plants and risk will be predicted for aquatic vascular plants. Additiona lly, EFED is aware that there are currently no listed algae or diatoms. For a complete ecologica l risk assessment, an analysis of how far from the use site risk to aquatic plants will occur is conducted. In order to c onduct this analysis it

must be known at what concentrations effects to aquatic plants will occur. This information will be used to assess the potential for direct and indirect effects to both nonlisted and listed species.Page 7 of 26 6. Comment: Page 4, Comment 2a states in regards to the data re quest for acute toxicity to freshwater invertebrates (O PPTS 850.1010), “In the Preliminar y Problem Document, Table D1 in Appendix B lists a numbe r of studies conducted with Daphnia (data are also available for midge) using technical material and TEP. The results for these studies were very comparable, with EC50 ranges from 3.6 to 4.4 mg/L, which greatly exceed expected

environmental concentrations of fluridone. Da ta with other species also yielded similar

results. Because there are several studies th at provide similar results, despite possible deficiencies, KTI does not believe that addi tional studies would yield new information.”

EFED Response: Freshwater invertebrate acute toxicity data for Daphnia (MRID 000103297) were fully reviewed since the publ ication of the problem formulation and found to be acceptable. EFED needs to be able to evaluate potential ex posure to current formulations of fluridone. EFED requests that the registrants provide EF ED with information on whether the studies completed with the previous end products are repr esentative of current products on the market. If they are not representative, studies examining toxicity of cu rrent end use products that are representative of current TEPs ar e still needed. More informa tion on data requirements for TEPs was added to Page 40 of the problem formulation.

7. Comment: Page 4, Comment 2a states in regards to the data re quest for acute toxicity to estuarine/marine oyster shell deposition (OPPTS 850.1025), “In the Preliminary Problem Document, Table D1 in Appendix B lists four studies conducted with the Eastern oyster.

There are two studies conducted with the techni cal material and two studies with TEP. The reported EC 50 values from two studies (technical material was 16.8 mg/L and TEP was 6.8 mg/L) are similar and far exceed the expected fluridone concentration in estuarine/marine environments; EC 50 values were not reported in the re maining two studies. The data from these four studies should be sufficient, desp ite possible deficiencies, for the Agency to conduct a risk assessment; new studies would not expect to materially change conclusions

that could be made from the available data.”

EFED Response: The two studies conducted for the easte rn oyster with the TGAI had highly variable exposure concentrations. In MRID 00103310, precipitation was observed in the test vessel and the concentration ranged from 70-102 % nominal. A 25% reduction in new shell growth was observed in the solvent control and at the 0.25 mg a.i./L test level. Treatment levels (0.1 – 1.4 mg/L, measured) were not high enough to detect a median eff ects concentration (EC 50 ) and it is not known at what exposur e level effects to oyster shell growth may occur. In MRID 00103311, measured concentrations (6.3-36 mg a.i./L ) ranged from 9-105% of nominal and four treatment levels exceeded solubility. Only two treatment (nominal of 6 and 10 mg a.i./L) levels had acceptable assayed concentrations (within 80 % of nominal) and were below solubility.

Effects were observed at one of those treatment levels. The effects con centrations cannot be

determined with the available informa tion. A study with TGAI is needed.

One study examining oyster shell deposition and exposure to TEP was submitted, MRID 00103314. In MRID, 00103314 treatment levels ranged from 0 – 1.0 mg a.i./L and no effects were observed at any treatment level. It is not know if effects woul d be observed at higher treatment levels. Additionally, precipitation was observed in stoc k solutions and fluridone was not detected in some samples. This study is not useful in determining whether the formulationPage 8 of 26 will influence the toxicity of fluridone, which is one reason these data are required. In MRID, 00103315, shell deposition was not examined. Theref ore, a study examining the toxicity of a representative TEP on oysters (O PPTS Guideline 850.1025) is needed.

Finally, effects endpoints are need ed in order to assess potential direct and indirect effects to nonlisted and listed species. These data will be used to determine how far from the treated site effects are likely to occur.

8. Comment: Page 4, Comment 2a states in regards to the data request for acute toxicity to estuarine/marine fish (OPPTS 850.1075), “ As with the previous examples, several sheepshead minnow studies were identified in Table D1 of Appendix B of the Preliminary

Problem Document. The results of these stud ies demonstrate LC50 values ranging from 10.7 to 18.1 mg/L and the species were exposed to concentrations exceeding the solubility of fluridone (and expected concentr ation of fluridone in aquatic habitat), the data should be sufficient to conduct the appr opriate risk assessments.”

EFED Response: Two studies were submitted examining toxicity to sheepshead minnow, MRIDs 00108837 and 00103316. In MRID 108837, acute to xicity of TGAI was examined. Two treatment levels exceeded solubility and con centrations were not measured in filtered or centrifuged samples. The dissolv ed concentration in water or exposure concentration cannot be

determined because concentrations of fluridone in some treatment levels exceeded solubility and

concentrations were not measured in filtered wate r or in centrifuged water. The test results do show that sublethal effects and mortality may occu r with exposure to fluridone. In order to examine risk to estuarine/marine fish, an accep table study examining acute toxicity of TGAI fluridone (OPPTS Guideline 850.1075) to estuarin e/marine fish is needed. In MRID 00103316, acute toxicity of fluridone TEP was examined. Two treatment levels exceeded solubility, test material precipitated out of solution, measured concentrations ranged from 44 – 93% nominal, and the initial and final water samples were combin ed. Therefore, the con centration over time is not known. Not enough information is available from this test to determ ine a reliable toxicity endpoint. In order to examine ri sk to estuarine/marine fish fr om exposure to fluridone TEP, an acceptable study examining acute toxicity of TEP (OPPTS Guideline 850.1075) to

estuarine/marine fish is needed.

9. Comment: Page 5, Comment 2a states in regards to the data request for acute toxicity to freshwater fish (OPPTS 850.1075), “ There are ample data on the toxicity of fluridone to

freshwater fish as are summarized in Table D1 of Appendix B of the Preliminary Problem

Document. Of the nine studies available, the LC50 data were very consistent, ranging from 5.6 to 22 mg/L. Given the ample and consistent da ta available for freshwater fish toxicity, new studies would not yield any new information that would be expected to change the risk assessment. As such, KTI requests the Agency reconsider the submission of these data.”

EFED Response: Freshwater fish acute toxicity data fo r rainbow trout, channe l catfish, bluegill, and fathead minnow with TGAI and TEP (M RID 000103297) were fully reviewed since the publication of the problem formul ation. Studies conducted for rainbow trout (coldwater species) and channel catfish (warmwater species) with TGAI are accep table. Additionally, studies examining toxicity to formulations are accep table for Rainbow trout and Fathead minnow.Page 9 of 26 Therefore, at this time we do not recomme nded a data call in for 850.1075 with TGAI for fluridone. The problem formulation was re vised on Page 15, 32, 34, 38, 54 and Appendix B to reflect this. Acute toxicity data for freshwater fish are needed that are representative of current typical end-use products (TEPs). EFED recomme nds that the registrant provide information on whether studies examining toxicity to EPs are ap plicable to current products or submit studies examining exposure to current end-use products that are representative of current TEPs for a coldwater and warmwater species. The tests shoul d be conducted with a species that also have

TGAI data available. Without these data it is not known if th e formulation results in greater toxicity than the active ingredie nt alone. More information on data requirements for TEPs was added to Page 40 of the problem formulation.

10. Comment: Page 5, Comment 2b states in regards to the ecological toxicity data requests,

“SePro will demonstrate that some of the data available are acceptable. Regardless of the fact

that there are numerous data on f ile to characterize the toxicity of fluridone, many of these studies were deemed invalid or supplemental, despite originally being considered acceptable. In its response and subsequent submission(s), SePro will provide additional information and support to demonstrate that many of the studie s should still be considered acceptable and no additional data should be required.”

EFED Response: EFED will evaluate the additional data submitted by SePro when it is

received.

11. Comment: Page 5, Comment 2c states in regards to the request for an environmental chemistry method in soil (OPPTS 835.6100), “The Agency has requested that environmental chemistry methods for soil (MRID 00159966) be validated with an independent lab validation (ILV). However, according to 40 CFR Part 158 (Footnote 7, 40 CFR 158.630), ILV soil data are only required when actua l or simulated field testing data are required/submitted. Actual or simulated field te sting data have not been submitted nor were data required to be submitted. In addition, soil is not considered a food/feed item and a

tolerance is not needed nor established for soil. As such, these data would not be supportive of any enforcement analytical method. KTI ac knowledges and agrees to submit ILV data for crayfish.”

EFED Response: EFED does not recommend we request a validated soil or sediment method at this time; however, if a state requests a validated method or a risk concern arises due to potential exposure to residues in soil or sediment, a validat ed method may be requested at that time. The problem formulation was updated to reflect this on Pages 31 and 63.

12. Comment: Page 6, comment 3a states in regards to data requested for NMF, “NMF is an aquatic photodegradate of fluridone, formed in la boratory photolysis studies at up to 74% of the applied amount of fluridone. NMF did not degr ade in lake or distilled water exposed to sunlight, but did completely degrade in lake water not exposed to light [Preliminary Problem

Document, EPA

‐ HQ

‐ OPP

‐ 2009

‐ 0160

‐ 0003].

In addition to being an aquatic photodegradat e of fluridone, NMF is on the TSCA inventory and is considered a high production volume (H PV) chemical with an estimated 1 to 10Page 10 of 26 million pounds produced and/or imported into the United States annually. It is primarily used for the production of pesticides and other agricultural chemicals, but it is also used as an extraction solvent for aromatic hydrocarbons. In other countries, it is a commonly used

solvent in the manufacture of el ectronics and chemical synthesis of resins [E. I. DuPont de Nemours and Co., 2005]. Because of its status as an HPV, the EPA has a substantial database on NMF, including ecological eff ects that can likely be used to satisfy the data gaps

identified in the fluri done registration review.”

EFED Response: The registrant should submit the speci fic studies and ra w data that are proposed to fulfill the data gaps for NMF. EF ED will review these data when they become

available.

13. Comment: Page 6-7, comment 3b states in regards to data requested for NMF, “As stated above, NMF is an aquatic photodegradate of fluridone, accounting for up to 74% of the applied amount in distilled wa ter and 36% in lake water. NMF is relatively stable to hydrolysis and photooxidation, but is readily bi odegradable and has a low persistence and low bioaccumulation potential [E. I. DuPont de Nemours and Co., 2005]. Indeed, several pond monitoring studies did not detect the presen ce of NMF after treatment of fluridone at normal and exaggerated rates [Osbourne et al , 1989; West et al, 1990; and Smith, et al, 1991].

NMF and fluridone were monitored in two Flor ida ponds in which fluridone was applied to achieve a concentration of 150 ppb in one pond and 466 ppb in the other pond [Osborne, et al, 1989]. Over 167 days, 59 water samples were analyzed for NMF a nd fluridone. No NMF was found at a detection limit of 2 ppm. West et al, 1990 monitored residues of NMF and fluridone in two Florida ponds in which flur idone was applied to each pond to achieve a fluridone concentration of 150 ppb. Over 167 da ys, 59 water samples were analyzed for

NMF and fluridone. NMF was not detected in any of the 192 water samples collected at a detection limit of 2 ppm. Hydrosoil samples ta ken 324 days after treatment did not contain any residues of NMF at a de tection limit of 0.005 ppm.

Fluridone was applied to two ponds in New Engl and to produce a fluridone concentration of 150 ppb [Smith et al, 1991]. Water samples were monitored for 18 months after application. Although the fluridone concentrations varied between the ponds due to the different formulations applied, NMF was never det ected in water samples from either pond.

Based on laboratory and field tests, it can be theorized that NMF biodegrades at a rate faster than it is formed through photodegradation of fl uridone, resulting in virtually no exposure of NMF to nontarget species.

Irrespective of the biode gradation of NMF, the fluridone application rates (and thus the potential NMF exposure), are low: the maximum single and combined application rate is 150 ppb. Even conservatively assuming that all of the applied fluridone photodegraded to NMF and that there was no further biodegradation of NMF, the resulting concentration of NMF would still be very low (possibly 27 μ g/L), and well below levels of toxicity demonstrated in the laboratory as discussed below. Indee d, in EPA’s 2004 drinking water assessment, thePage 11 of 26 estimated peak acute and chronic exposure to NMF was 2.64 μ g/L and 1.45 μ g/L, respectively, based on an app lication rate to drinking wate r systems of 20 ppb [U.S. EPA, 2004].

Since fluridone applications are made direc tly to water, the expos ure of fluridone to terrestrial matrices, such as bird s, is expected to be minimal at best. It is unlikely that birds would be exposed to NMF from terrestrial feed items since formation of NMF is expected to occur by photodegradation of fluridone in wate r, not on soil. Birds c onsuming water treated with fluridone would also not be exposed to significant levels of NMF since the maximum fluridone concentrations is 150 ppb and thus resulting NMF would be less than 27 ppb.

Furthermore, because NMF is a photodegradate of fluridone, aquatic nontarget species would have already been exposed to NMF through fluri done testing. Nearly a ll of the ecotoxicology tests require exposure to light . As such, fluridone would na turally degrade to NMF during

these studies and result in inadvertent e xposure to NMF, meaning data developed for fluridone would support the NMF requirement s for fluridone regi stration review.”

EFED Response: EFED would not expect NMF to be pres ent at the limit of detection of 2 ppm with 150 ppb concentrations of fluridone. Monito ring data should have a limit of detection that can detect NMF at concentrations that are expect ed to be present in the environment and that may be of a risk concern.

Birds may be exposed in the terre strial environment to NMF and fl uridone. Fluridone may occur

in the terrestrial environment in water and t hus photodegradation in water may occur in the

terrestrial environment. Fi nally, photodegradation is not necessarily the only possible degradation pathway that NMF may form.

It is not possible to determine the exposure level to birds and mammals that may result in risk without toxicity data on NMF.

14. Comment: Page 7, comment 3c states in regards to data requested for NMF, “The available data for NMF indicate that the potential for acute toxicity to aquatic species is low. Dimethyl formamide (DMF) also has a low potential fo r toxicity to aquatic species. DMF is structurally similar to NMF in that they both contain an N substituted formamide moiety; DMF contains two methyl groups, whereas NMF contains one methyl group. For purposes of the HPV program, the Agency considers DMF to be a suitable surrogate for NMF [E. I. DuPont de Nemours and Co., 2005]. Some of the key data addressing several of the Agency’s data gaps are summarized below:”

The registrant summarizes several ecologi cal effects data for NMF and DMF.

EFED Response: The registrant should either submit da ta (along with the raw data) or clearly identify what HPV data they would like the Ag ency to use to fulfill the data requirement for

NMF. EFED will review the identified data fo r potential use in the evaluation of risk from exposure to NMF. At this time, EFED does not c onsider data on DMF to be a suitable surrogatePage 12 of 26 for NMF. The data requirements for the HP V program and FIFRA are different and thus a determination by the HPV program is not applicable to the FIFRA program.

15. Comment: Page 9, comment 4b states in regards to potential exposure of Nontarget species to 3-TFMBA, “As stated above, 3

‐ TFMBA is an aquatic phot odegradate of fluridone, accounting for up to 24% of the applied amount in distilled water and 33% in lake water. Available data for benzoic acid can be used as a surrogate for 3

‐ TFMBA. Benzoic acid has been shown to rapidly degrade by photodegr adation (90% after 140 minutes), readily biodegrades (> 90% after 28 da ys) under both aerobic and anae robic conditions, and does not bioaccumulate [OECD, 2001]. Benzoic acid is stable to hydrolysis. The main pathway for

elimination in the environment is through biotic mineralization. Although 3

‐ TFMBA may be present in waters treated with fluridone, it would show similar degr adation properties as

benzoic acid.

Irrespective of the biodegradation of 3

‐ TFMBA, the fluridone app lication rates (and thus, potential aquatic exposure to 3

‐ TFMBA) are low: the maximum single and combined application rate to water is 150 ppb. Even cons ervatively assuming that all of the applied fluridone photodegraded to 3

‐ TFMBA and that there was no further biodegradation of

3

‐ TFMBA, the resulting concentration of 3

‐ TFMBA would still be very low, and well below levels of toxicity demonstrated in the laboratory as discussed below. Terrestrial exposures to

3

‐ TFMBA would not be expected since flurid one is applied directly to water, and photodegradation of fluridone to 3

‐ TFMBA on terrestrial matri ces is not expected.”

EFED Response: EFED believes that the chem istry of the two compounds (3- trifluoromethylbenzoic acid, e.g ., 3

‐ TFMBA, and Benzoic acid) is different and therefore; any conclusions regarding the fate of 3

‐ TFMBA should not be made at th is point. EFED continues to

ask for data for 3

‐ Trifluoromethyl Benzoic Acid (3

‐ TFMBA).

16. Comment: Page 9, comment 4c states, “No data are available for 3

‐ TFMBA but it is structurally similar to benzoic acid in that both chemicals contain both an aromatic ring moiety and a carboxylic acid moiety; 3

‐ TFMBA bears an additional moiety, a trifluoromethyl group. Benzoic acid should be a suitable surrogate for 3

‐ TFMBA. Some of the key data addressing several of the Agency’s data ga ps are summarized belo w:” The registrant

indicates that studies on acute oral avian toxicity and av ian reproduction are not needed because it is unlikely that birds will be exposed to this degradate.

EFED response: EFED believes that birds may be expos ed in the terrestrial environment to 3- TFMBA in spray drift from aerial and ground broadcast applications. Birds may also be exposed to 1) drinking water as fluridone is applied directly to water that may serve as an important source of drinking water for birds and 2) waterf owl swim, feed, and drink water that may be

treated with fluridone. Fate data on 3-TFMB A are not available for EFED to understand its environmental fate and discount potential exposur e. Therefore, studies on acute oral avian toxicity and avian reproduction are needed to evaluate potential risk to birds from exposure to 3-

TFMBA.Page 13 of 26 17. Comment: Page 10, comment 5 provides information requested to assist in the ecological

risk assessment.

EFED Response: EFED will use the available informa tion when the ecological risk assessment is completed. The information provided is specifi c to one label. When EFED performs the risk assessment, parameters on all labels will be evalua ted. As there are no restrictions on the labels on reapplication interval s or number of applications per ye ar, a conservative assumption that

results in a reasonable chronic ma ximum exposure estimate to flur idone will be made to estimate exposure. For the geographic restrictions for stat es and U.S. territories, it will be assumed that fluridone may be used in all states and U.S. terri tories unless the label speci fically states that the product may not be used in those area. This is because regulatory changes made by states and territories may occur without changing the national label and the Federal Action is based on what is specified on the EPA label.



### C. SePRO Corporation (SePRO), a ma nufacturer of fluridone (EPAHQ-OPP-0160-0040)

1. Comment: Page 3 states “Guideline 850.1300, Aquatic Invertebrate Life Cycle: Daphnid –

The Summary Document states the study needs to be conducted using TGAI while the Preliminary Problem Formulation Document states that TGAI and typical end-use product (TEP) are required. We believe that the data requirement listing for TEP is in error and should not be promulgated to the Final Wo rk Plan and subsequent Data Call-In.”

EFED Response: Data on the TEP are not required fo r OPPTS Guideline 850.1300. This typo is corrected in the revised problem formulation.

2. Comment: Page 3 states, “Guide line 850.1400, Freshwater Fish Early-life Stage (TGAI) –

The Summary Document states this study is required; how ever, it is not listed as required anywhere in the Preliminary Problem Formulation Document and no justification for the requirement of the study is identif ied. We believe the data requ irement listing is in error and should not be promulgated to the Final Wo rk Plan and subsequent Data Call-In.”

EFED Response: The fish early-life stage study fo r freshwater organisms (850.1400) is recommended for all outdoor end-use products for a species that also has acute data (40 CFR Part 158.630, see footnote 1 and 13 of Terrestri al and Aquatic Nontar get organism Data Requirements Table). The reason that data are neededfor the same species is so that an acute-tochronic ratio may be calculated a nd used to estimate chronic toxici ty endpoints to more sensitive species. Acute-to-chronic ratios may be calculated using either da ta from a fish early life stage study or a fish full life cycle study. An acceptable fi sh full-life cycle study is available for the fathead minnow (MRID 00103309). Also, acute da ta on the EP for the Fathead minnow were reviewed since the completion of the problem formulation and found to be acceptable. A study on the TGAI is preferred; however, data for Rain bow trout and Channel catfish indicate that the EP tested did not influence the toxicity of flur idone. In the absence of an acute study on the TGAI, the 96-hr LC 50 for the EP for the Fathead minnow wo uld be used to estimate an ACR.

The estimated ACR is 17.3 based on a 96-hr LC 50 of 8.3 mg a.i./L for the EP (MRID 00103297). Additionally, the weight of evidence does not indicat e a need for additional chronic data on fish. Both the Chinook salmon early life stage study (MRID 45915601) and Fathead minnow full-lifePage 14 of 26 cycle study (MRID 00103309) have similar No-Obs ervable-Adverse-Effects-Concentrations (NOAECs). Based on the weight of evidence, EFED is not recommending that an early-life stage study (OPPTS Guideline 850.1400) or full life-cycle study (OPPTS Guideline 850.1500) be requested for a species with acute data at th is time. The problem formulation was updated to reflect this on Pages 16, 32, 35, 36, 38, and 54.

3. Comment: Page 3 states “Guideline 850.1500, Fr eshwater Fish Life Cycle (TGAI) – SePRO requests that EPA classify this data re quirement as “Reserved”. Acceptable fish life cycle data are available w ith fathead minnow (MRID 00103309). Acceptable acute toxicity data with the fathead minnow (MRID 00103297) and public literature data are also available, which should eliminate the requirement for this perceived data gap.”

EFED Response: Based on the weight of evidence, EFED is not recommending that an earlylife stage study (OPPTS Guid eline 850.1400) or full life-cy cle study (OPPTS Guideline 850.1500) be requested for a species with acute data at this time. The problem formulation was updated to reflect this on Pages 16, 32, 35, 36, 38, and 54. See the response to the previous comment 2 for a full explanation.

4. Comment: Page 4 states “EPA preliminarily requested additional data concerning the toxicity of NMF and 3-TFMBA (MRID 00103326). SePRO has reviewed its available data and the public literature and be lieves that, when the body of li terature concerning fluridone dissipation and degradation is c onsidered, it can be logically concluded that neither NMF nor 3-TFMBA is likely to accumulate in fluridone -treated water systems. Therefore, SePRO believes that no potential exposure to NMF or 3-TFMBA is likely, thus eliminating the EPA’s concern for potential exposure and the n eed for data on either potential photolytic degradate.”

EFED Response: At this time, we do not have enough information to conclude that exposure to

NMF and 3-TFMBA would be minimal. Theref ore, toxicity data on NMF and 3-TFMBA are

still needed to evaluate the risk of exposure to these compounds.

5. Comment: Page 4 and 6 discuss environmental fate information that is proposed to be used to in the exposure assessment for NMF and 3- TFMBA. EFED has an overall response and some individual responses to some of the comments below.

Overall EFED Response: Please submit all available data and public literature for review by the Agency and it will be considered for potential use in the exposure assessment.

1. Comment: Page 4, “given that the ma jority of UV-B radiation is filtered/adsorbed by the DOC that is presen t in natural pond/lake systems, the rate of photolytic breakdown of fluridone (and, consequently, the rate of NMF and 3- TFMBA production) in the field will be much slow er than represented in Saunders and Mosier (1983). In fact, the half-life of fluridone observed and measured in a field study incorpora ting 40 fluridone-treat ed ponds and lakes averaged 20 days and resulted from not only photolysis, but also from dissipation

and dilution into untreated waters and ad sorption onto plants (West et al., 1983).”Page 15 of 26 EFED Response: EFED recognizes that the rate of phot olysis of fluridone in the field will depend on exposure to sunlight. Indeed, field di ssipation half-lives are discussed under Section 3.3.1.c Aquatic Field Dissipation of the problem formulation.

2. Comment: Page 4 states “...a Zahns-Welle ns biodegradation test with NMF

conducted in 2005 indicates that this compound is readily biodegraded (Mongan 2005).”

EFED Response: EFED will review the Zahn-Wellens bi odegradation test with NMF when it is submitted to the Agency.

3. Comment: Page 5 states “Consequently, it can be estimated from available

literature data and fate models that NM F is produced at a rate of 0.0038 day-1, but is degraded at a rate of 0.046 day-1, indicating that this compound biodegrades twelve times (12x) faster than it is fo rmed. Similarly, 3-TFMBA is calculated to form at a rate of 0.0044 day-1, but biodegrad es at a rate of 0.018 day-1, about four times (4x) faster than formation. Ev en a simple comparison of fluridone photolysis half-life under natural condition (33 days) with the half-lives of the degradants of concern (15 and 37.5 days for NMF and 3-TFMBA, respectively) indicates that the potential for buildup of these products is extremely low.” The next paragraph discusses monitoring data for to support the exposure analysis for

NMF and 3-TFMBA

EFED Response: EFED will review environmental fate data and environmental monitoring data

on NMF and 3-TFMBA when it is submitted to th e Agency. With regard to the referenced monitoring data from the state of Michiga n, according to (Michigan Department of Environmental Quality “Guidance for Fluridone Residue Sampling):

Sampling Frequency

LAKES AND PONDS Application at 6 ppb with a one time bump- up treatment to raise the concentration back to 6 ppb. 1. Sample all sites between 48 and 60 hours after the initial treatment. 2. Sample all sites at 14 days post-treatment. 3. Sample all sites at 30 da ys post initial treatment. 4. Sample all sites at 60 da ys post initial treatment.

Based on the fate properties of fl uridone, and its fast photolysis de gradation rate (with a half -

lives 34 hours in natural pond water, MRID# 103326); following the suggested sampling frequency routine could result in missing peaks concentrations. Also, major photodegradation degradates (NMF and 3CF 3 - Benzoic acid), were not includ ed in such sampling protocol.

6. Comment: Page 6 identifies the following pot ential data requirements for NMF.

• Freshwater Invertebrate Acute T oxicity (OPPTS Guideline 850.1010);Page 16 of 26 • Acute Toxicity Freshwater Fish: Coldwate r and Warmwater Species (OPPTS Guideline 850.1075);

• Freshwater Invertebrate Life Cycle: Daphnid (O PPTS Guideline 850.1300);

• Freshwater Fish Early-Life Stage and Es tuarine/Marine Early-Life Stage (OPPTS Guideline 850.1400);

• Avian Acute Oral Toxicity (OPPTS Guideline 850.2100); and

• Avian Reproduction (OPPTS Guideline 850.2300).

EFED Response: EFED concurs that these data are nece ssary to evaluate risk to organisms due to exposure to NMF. The problem formula tion was updated on Page 32 to include OPPTS

Guidelines 850.1300 and 850.1400. These studies are also listed in the Data Call In tables in Appendix A.

7. Comment: Page 6 comments on the potential ex posure of Nontarget Species to NMF.

EFED has an overall response and some individual responses to some of the comments below.

Overall EFED Response: Please submit all available data and public literature for review by the Agency and it will be considered for potential use in the exposure assessment.

a. Comment: Page 6 states, “...the potential a quatic exposure to NMF is low when considering that the maximum allowable in-water dose of fluridone is 150 ppb (including multiple applications).”

EFED Response: EFED cannot evaluate whether eff ects with exposure to NMF will occur without a full exposure assessment and data examin ing at what concentrati ons effects are likely to occur. EFED will evaluate this when data are submitted to the Agency.

b. Comment: Page 6 states, “It is unlikely th at birds would be exposed to NMF from terrestrial feed items since formation of NMF is expected to occur by photodegradation of fluridone in water, not on soil. Birds consuming water

treated with fluridone also would not be exposed to significant levels of NMF

since the maximum fluridone concen tration would be 150 ppb which could hypothetically result in a maximu m potential NMF level of < 27 ppb. However, as noted above, SePRO does not believe th ere will be any chance for potential exposure to NMF as the degradation rate exceeds the formation rate.”

EFED Response: EFED cannot evaluate whether eff ects with exposure to NMF will occur without a full exposure assessment and data examin ing at what concentrati ons effects are likely

to occur. EFED will evaluate this when da ta are submitted to the Agency and when the ecological risk assessment is performed.

8. Comment: Page 7 states, “Available studies we re conducted with NMF and/or dimethyl formamide (DMF), considered under the HPV pr ogram to be a suitable surrogate for NMF (US EPA 2009b)” Additionally, SePRo identif ies acute and chroni c toxicity data on

freshwater fish and invertebrates for NMF and DMF available through the HPV program.Page 17 of 26 They propose that the HPV data should be used fulfill the data gaps on effects data for NMF as a degradate of fluridone, a pest icide applied directly to water.

EFED Response: The document cited as making a determination that DMF is a suitable surrogate for NMF clearly states on the title Page, “determinations as to risk or final

determinations as to whether sufficient data ar e available to characterize risk. They are based predominantly on screening-level hazard, exposure, and risk characterizations prepared by EPA using data submitted to the Agency under the HPV Challenge Program1 and the 2006 Inventory Update Reporting (IUR)2, and data publicly available through ot her selected sources. These screening-level characterizations do not constitute full risk as sessments. They are intended only to support initial decisions to determine the relative priority for further assessment or risk management activities concerning HPV chemicals, and to identify data needs for individual chemicals or chemical categor ies” (USEPA, 2009). The deci sion only applies to the HPV Challenge Program and the ChAMP program. Add itionally, the document also states that the decisions are based on an assumption of low like lihood of exposure because NMF is mainly used as an intermediate. For example, Page 1 stat es, “Because of the high developmental toxicity associated with this chemical, EPA notes that occupational exposures of women of childbearing age should be avoided. The chemical’s use as an intermediate is expected generally to limit potential exposures.” These dete rminations are not applicable to degradates of pesticides and risk assessments conducted on degradates of pest icides that are released directly into the terrestrial and aquatic environment. Clearly, the potential for exposure to NMF under this use scenario is high. EFED will cons ider available data for N-methyl formamide for potential use in the ecological risk assessment. The registrant should identify each HPV study they propose to be used in the ecological risk assessment. EFED will evaluate these when they are received and data are fully evaluated.

9. Comment: Page 8 states, “The EPA has identif ied the following list as potential data requirements on 3-TFMBA:

• Avian Acute Oral Toxicity (Guideline 850.2100); and

• Avian Reproduction (Guideline 850.2300). “

EFED Response: EFED concurs that these are the potenti al data requirements for 3-TFMBA. These are identified on Page 32 of the problem formulation.

10. Comment: The first paragraph on Page 8 proposes that the environmental fate data for

benzoic acid should be used for 3-TFMBA.

EFED Response: EFED believes that the chemis try of the two compounds (3

‐ TFMBA and Benzoic acid) is different and therefore; any conclusions regarding the fate of 3

‐ TFMBA should not be made at this point. EFED continues to ask for data for 3

‐ Trifluoromethyl Benzoic Acid (3

‐ TFMBA).

11. Comment: SePro indicates that th e potential for exposure to 3-TFMBA is low due to the low application rate of fluridone in water and the effects endpoint s and terrestrial exposure is not expected because fluridone is applied dir ectly to water and photodegradation of fluridone

to 3-TFMBA on terrestrial ma trices is not anticipated.Page 18 of 26 EFED Response: Degradation of fluridone is also likel y to occur in the te rrestrial environment and 3-TFMBA may form. Birds may be exposed to 3-TFMBA in dietary items receiving spray

drift in the terrestrial environment and in drinking water containing 3-TFMBA.

12. Comment: SePro indicates that acute avian data on benzoic acid may be used as a surrogate for 3-TFMBA. Additionally, SePro indicates that chronic exposure to birds is expected to be minimal and therefore, chr onic data are not needed.

EFED response: EFED believes that the chem istry of the two compounds (3

‐ TFMBA and Benzoic acid) is different. The toxicity of 3-TFMBA cannot be predicted based on data for benzoic acid. Additionally, the directions for flur idone use indicate that fluridone should be held at a concentration of 150 ppb for 30 to 90 days and does not have a ny reapplication restrictions. It could be applied at 150 ppb to a water body th roughout the year. This would result in chronic exposure to fluridone and its degradates despite the rates of degrada tion of the parent and degradates. Birds use water bodies as a water source and food source. EFED believes that chronic exposure of birds to 3-TFMBA is likely. Therefore, EFED recommends that the Agency request data on chronic toxicity of 3-TFMBA to birds (OPPTS guideline 850.2300).

13. Comment: On Page 10 SePro reiterates the request that EFED review the HPV data that could potentially be used to fulfill the data requests for NMF and 3-TFMBA.

EFED Response: EFED will review data available from the HPV program on NMF for potential use in the ecological risk assessment in the evaluation of potential exposure to NMF; however, the quality of the HPV data must be cons istent with the data quality requirements for

other studies submitted under FIFRA in order to use the data in the risk assessment.

13. Comment: On Page 10 SePro states, “because NMF is a photodegradate of fluridone, aquatic nontarget species would have alrea dy been exposed to NMF through testing, as nearly all of the ecotoxicol ogy tests require exposure to li ght. As such, fluridone would naturally degrade to NMF during these studies and result in inadvert ent exposure to NMF, meaning data developed for fluridone woul d support the NMF requirements for fluridone registration review.”

EFED Response: It is possible that organisms were exposed to NMF during the ecological toxicity studies conducted on flurid one; however, it is not known at what concentrations and how consistent that exposure was overtim e. Therefore, the available da ta cannot be used to evaluate the risk of potential exposure to NMF.

14. Comment: Page 10 states, “EPA stated that th e environmental chemistry methods for soil (MRID 00159966) and crayfish (MRID 00162775) need to be validated under an independent lab validation (ILV). According to 40 CFR 158, ILV is required for any chemical for which there may be exposure from human food or livestock feed, either through direct application or bioaccumulation. Because ther e is a tolerance for fluridone in crayfish, it is appropriate to have a method that has been independently verified. EPA should not need an ILV for the soil method as requested because fluridone is not applied directly to anyPage 19 of 26 terrestrial crop. Additionally, based on the discussion found on page 3 of this document, exposure to NMF via application to fluridone is not anticipate d; therefore, an analytical method is not required for NMF nor is an ILV of the analytical method.”

EFED Response: EFED does not recommend we request a validated soil method at this time; however, if a state requests a validated method or a risk concern arises due to potential exposure to residues in soil or sediment, a validated met hod may be requested at that time. The problem formulation was updated to reflect this on Pages 31 and 63. The analytical method for crayfish

should be validated for fluridone and NMF as exposure to both fluridone and NMF may occur

with the use of fluridone.

15. Comment: On Page 17 SePro requests that EFED formally review MRID 00103297 acute toxicity studies on fish for potential use in the risk assessment and to fulfill the data gaps identified for acute toxicity to freshwater fish.

EFED response : Freshwater fish acute toxicity data for rainbow trout, cha nnel catfish, bluegill, and fathead minnow with TGAI and TEP (M RID 000103297) were fully reviewed since the publication of the problem formul ation. Studies conducted for rainbow trout (coldwater species) and channel catfish (warmwater species) with TGAI are accep table. Additionally, studies examining toxicity to formulations are accep table for Rainbow trout and Fathead minnow. Therefore, at this time we do not recomme nded a data call in for 850.1075 with TGAI for fluridone. The problem formulation was re vised on Page 15, 32, 34, 38, 54 and Appendix B to reflect this. Acute toxicity data for freshwater fish are needed that are representative of current typical end-use products (TEPs). EFED recomme nds that the registrant provide information on whether studies examining toxicity to EPs are ap plicable to current products or submit studies examining exposure to current end-products that are representative of current TEPs for a coldwater and warmwater species. The tests shoul d be conducted with a species that also have

TGAI data available. Without these data it is not known if th e formulation results in greater toxicity than the active ingredie nt alone. More information on data requirements for TEPs was added to Page 40 of the problem formulation.

16. Comment: Page 17 states, “ Bluegill acute st udy (850.1075) [MRID 00103308 ] – The Agency has downgraded this study from acceptable to supplemental . SePRO is currently reviewing EPA’s memorandum dated September 2, 2009 and will provide a detailed response to the Agency related to this data re quirement. At this time, we do not agree with the Agency’s opinion to downgrade the study."

EFED response: In MRID 00103308, concentrations were measured in every third test

container at the initiation and termination of th e study. The water was not centrifuged or filtered prior to measuring the concentration in water and the total organic carbon in the water was not

measured. Measured fluridone concentrations in water ranged from 81 - 130% of nominal. While the observation of precipitate was not repo rted, the three highest concentrations tested exceed the solubility of fluridone in distille d water (12.3 mg/L) (USEPA, 2004). Because the fluridone concentrations were higher than solubi lity and the measured c oncentrations were not specific to the dissolved concentration, e.g ., were not measured after filtering or centrifugation,Page 20 of 26 the true exposure concentration cannot be determined. 2 It was not recognized at the time that the

measured concentrations were not the dissolved concentration; however, th is has always been a standard requirement in aquatic t oxicity guidelines. Th e study still has valuable information and is considered supplemental. Mortalities occurre d at nominal concentrations of 12.5 and greater. As fluridone degrades rapidly via aqueous photolysis (aqueous phot olysis half-life ranged from 0.9-2.4 days; MRID 00103326) measured concentrations in acute tests are need ed to verify that exposure was constant over time. All of these va riables taken together in dicate that the exposure

concentrations in the tests are uncertain and the study may not be used quantitativel y in the risk

assessment.

17. Comment: “ Salmon early life stage st udy (850.1400) [MRID 46112001] – EPA listed this study as an acute toxicity st udy (850.1075); however, it is actua lly an early life stage study performed by Columbia National Fisheries Laboratory in 2002 following OPPTS Guideline 850.1400. Eggs and fry of Chinook salmon, Oncorhynchus tshawytscha , were exposed for 61 days to five concentrations of fluridone TGAI or to one conc entration of Sonar® (TEP) and egg hatchability, fry survival, and growth were quantified. There were four replicates per treatment with 25 eggs per chamber. Actual concentrations varied between 106-111% of nominal. All water parameters were within required limits. This study is considered an acceptable early life stage study with a coldwater fish, and supplemental for Sonar® (only a single concentration was tested). While not dir ectly testing 96 hr su rvival as an endpoint, there were no treatment-related mortalities of egg, fry, or adults in this test, resulting in a NOEC >1.6 mg/L, equivalent in sensitivity to walleye exposed to the TEP (Sonar®). SePRO requests the EPA to use these data to fulfill the requirement for a coldwater fish acute survival study (850.1075) as indicated in the EPA table.”

EFED Response: MRID 46112001 is an acute toxici ty study on Chinook salmon and a seawater adaptability test. In the acute toxicity study (M RID 46112001) an acute endpoint was not available, e.g ., 96-hr LC 50 >5.76 mg/L; therefore, this study may not be used to fulfill the acute toxicity to coldwater fish (OPPTS Guid eline 850.1075). However, studies are available

on the Rainbow trout and Channel Catfish. EF ED does not recommend that OPPTS Guideline 850.1075 with TGAI be requested at this time . MRID 45915601 is an early life stage study (OPPTS Guideline 850.1400) on Chinook salmon that was fully reviewed since the preliminary problem formulation was completed. This was updated in the on Page 15, 35, and 69.

18. Comment: SePro listed several open literature studies that could be used to fulfill the data requirement for OPPTS Guideline 850.1750 usi ng the TEP for the rainbow trout, fathead minnow, and bluegill.

EFED Response: Data are needed that are representa tive of current TEPs. The registrant should provide information indicating whether studi es examining toxicity to EPs are applicable to current products or submit st udies examining exposure to curre nt EPs that are representative

of current TEPs for a coldwater and warmwater species. The tests should be conducted with a species that also have TGAI data available. A discussion on the need for data on TEPs was added to Page 40 of the problem formulation.

2 The analytical method was re ported submitted in Appendix C. However, appendix C was not available for review.Page 21 of 26 19. Comment: SePro states on Page 20, “ Sheepshead minnow acute toxicity studies (850.1075) [MRIDs 00108837 and 00103316 ] – The Agency has downgraded this study from acceptable to supplemental . SePRO is currently review ing EPA’s memorandum dated September 2, 2009 and will provide a detailed re sponse to the EPA related to this data requirement. At this time, we do not agree with the EPA’s opinion to downgrade the study.”

EFED Response : In MRID 00108837, toxicity of fl uridone was tested at nominal concentrations of 0.0 (control), 0.0 (solvent cont rol with 1.5 mL N,N-dimethylformamide in 3 L seawater), 3.0, 6.0, 12.0, 25.0, and 50.0 mg/L. Water samples were collected from test containers at the beginning and end of the study and combined. Measured concentrations were
between 96 and 103% of nominal. The dissolved fluridone concen tration in water or exposure

concentration cannot be determined because concen trations of fluridone in some tests exceeded solubility and concentrations were not measured in filtered water or after centrifugation. The test results do provide some useful information and ar e therefore determined to be supplemental. Sublethal effects and mortality may occur at c oncentrations near 1-12.3 mg/L. As the exposure concentration is not known, the study results may only be used qualitatively. The fact that approximately 100% of fluridone was measured at treatment levels that exceeded solubility illustrates that the filtered or centrifuged water samples need to be measured to estimate actual exposure concentrations.

MRID 103316 was not recently downgraded but was classified as supplemental in 1981 when it was initially reviewed. Based on the variability in the measured concentrations compared to nominal concentrations, the presence of preci pitate and the test concentrations exceeding solubility the true exposure con centration is not known. Nominal concentrations ranged from 3- 50 mg/L. Mortality was observed at 12 mg/L and a bove. Water was filtered prior to analysis. Measured concentrations range d from 44-93% of nominal.

EFED considers both of these studies to be suppl emental and will use the da ta qualitatively in the assessment. EFED will consider SePro’s request to upgrade the study when it is received. These studies do not fulfill the data requirement of 850.1075 for estuarine/marine acute toxicity to fish using the TGAI and TEP.

20. Comment: SePro identified an open literature st udy (Riley and Finlayson, 2004) that could potentially be used to fulfill the data requirement for OPPTS Guideline 850.1075 acute toxicity to estuarine/marine fish using the TEP.

EFED Response . EFED will review any open literature submitted to fulfill the data requirements for any effects endpoint. EFED re quests that SePro submit the studies proposed to

fulfill OPPTS Guideline 850.1075. The raw data supporting the studies should also be

submitted.

21. Comment: Page 20-21 states, “ Daphnia magna chronic study (850.1010 and 850.1300) [MRID 00103297 ] – This study has not yet be en reviewed by EPA for validity. EPA lists this as: preliminary/supplemental . SePRO has reviewed this study and believes it meets EPA requirements for acceptability. SePRO requests that the EPA review this study in its entiretyPage 22 of 26 and determine if the study satisfies this data requirement. We further request that the EPA provide a data evaluation record for this review.”

EFED Response: Freshwater invertebrate acute toxicity data for Daphnia (MRID 000103297) were fully reviewed since the publ ication of the problem formulation and found to be acceptable. EFED needs to be able to evaluate potential ex posure to current formulations of fluridone. EFED requests that the registrants provide EF ED with information on whether the studies completed with the previous end products are repr esentative of current products on the market. If they are not representative, studies examining t oxicity of current EPs th at are representative of

current TEPs are still needed. More informati on on data requirements for TEPs was added to Page 40 of the problem formulation.

EFED is in the process of preparing a Data Evaluation Record for the 850.1300 (MRID 00103297). All of the chronic t oxicity studies conducted on Daphnia magna did not have

measured concentrations available for the test s because the samples we re stored too long (see Page 409 of the study report). Therefore, these studies cannot be used to fulfill the OPPTS Guideline requirement of 850.1300.

22. Comment: SePro discussed two open literature studies and proposes that they may be used

to fulfill the Daphnia magna chronic toxicity stud y data requirements.

EFED Response: EFED will review any open literature data submitted to fulfill the data requirements for any effects endpoint when data are received. EFED requests that SePro submit studies, along with raw data, proposed to fulfill OPPTS Guideline 850.1300.

23. Comment: Page 21 states, “ Eastern oysters embryo acut e toxicity st udies (850.1055) [MRIDs 00103311 and 00103315 ] – The Agency has downgraded this study from acceptable to supplemental . SePRO is currently review ing EPA’s memorandum dated September 2, 2009 and will provide a detailed res ponse to the Agency related to this data requirement. At this time, we do not agree with the EPA’s opinion to downgrade the study

to.”

EFED Response: In MRID 00103311, Toxicity of fl uridone was tested at nominal concentrations of 0.0 (control), 0.0 (solvent co ntrol with 0.9 mL dimethylformamide in 1-L seawater), 6.0, 10.0, 32.0, 56.0, 100.0, and 320.0 mg/L. Wa ter samples were collected from each replicate of each treatment and the controls at the initiation and completion of the test for chemical analysis. The initial and terminal samples were composited for each replicate.

Concentrations of fluridone were measured in composite samples after f iltering (Schleicher and Schuell analytical filter paper, 12.5 cm, pore size not specified). Measured concentrations were 9-105% of nominal with the lowest recovery observe d at the highest test c oncentrations. Actual exposure concentrations cannot be determined because of the uncertainty in the measured

fluridone concentrations. The f actors contributing to this unce rtainty include 1) the samples from different time points were combined prior to analysis, 2) some exposure concentrations exceeded solubility in distilled water, 3) the percent of nominal concentrations were highly variable, and 4) the pore size of the filter was not specified. It was not recognized at the time that the measured concentration was not a good reflection of the dissolved concentration;Page 23 of 26 however, this has always been recommended in th e guideline requirements for aquatic toxicity

tests. The test results do show that a reduction in normal larvae may be expected at exposure concentrations near 10 mg/L and above. Therefor e, the study is classified as supplemental and may be used qualitatively. This study does not fu lfill the data requirement for acute toxicity of fluridone to eastern oysters (OPPTS Guideline 850.1055).

MRID 103315 was determined to be supplemental wh en it was initially re viewed in 1982. The original DER states that the st udy could not be used to fulfill the guideline requirement for acute toxicity test using the formulated product on th e embryo-larvae of an oys ter species. The DER states, “Because solubility probl ems and/or possible losses of test material from aeration, exposure from the formulated product cannot be qua ntified.” Additionally, three of the nominal

test concentrations were above th e solubility of fluridone. This leaves only three treatment levels below the level of solubility. Therefore, the stud y is classified as supplemental and may be used qualitatively. This study does not fulfill the data requirement for acute toxicity of fluridone to eastern oysters (OPPTS Guideline 850.1055). EF ED will review any additional information submitted by SePro on this study when it is submitted.

24. Comment: Page 23 states, “ Eastern oysters shell deposition acute toxicity studies (850.1025) [MRIDs 00103310 and 00103314 ] – The Agency originally listed these studies as supplemental . SePRO is currently reviewing the studies and will provide a detailed response to the Agency related to this data re quirement.” Additionally, SePro indicates that

treatment levels in these studies we re above the level of solubility.

EFED response: In MRID 000103310 conducted with the TGAI, only 25% reduction in shell growth was observed and an effects endpoint for th e study is not available. The highest tested measured concentration was 1.4 mg/L. This study should be repeat ed at higher exposure

concentrations. None of the tr eatment levels were above the so lubility (12.3 mg/L) of fluridone.

In MRID 00103314 conducted with Sonar AS, a no effect level was not determined and solubility problems and possible losses of the test material from aeration were observed. Fluridone was not detected in three water samp les and measured concentrations were highly variable. For example, at the 1 mg/L treatmen t level the first measured concentration showed 0.08 mg/L and the second measured concentratio n was at 0.62 mg/L. Clearly, it is not known whether exposure concentrations were constant over time. In fact, it appears that initial exposure

concentrations were much lower than the final exposure concentrations. None of the treatment

levels were above the solubil ity (12.3 mg/L) of fluridone.

25. Comment : Page 23 states, “ Mysid shrimp acute toxicity studies (850.1045) [MRIDs

00112789 and 00103312 ] – The Agency originally listed these studies as supplemental

. SePRO is currently reviewing the studies and will provide a detailed response to the Agency related to this data requirement.”

EFED Response: MRID 112789 is classified as accepta ble, see Page 16 35, and 69 of the problem formulation.Page 24 of 26 In MRID 00103312 using the TEP, a water sample was collected at the beginning of the test and at the end of the test, combined, filtered, and then the concentration was measured. Measured concentrations were 60-100% of applied. It is not known if the test concentrations were consistent overtime. Therefore, the study may not be used to fulfill OPPTS Guideline requirement for 850.1045.

26. Comment: Page 23 states, “Additional public literature is ava ilable on the acute toxicity values for blue crabs (96 hr LC50, technical and formulation), oyster embryos (48 hr EC50 shell deposition, technical and formulated), and pink shrimp (96 hr LC50, technical and formulated). SePRO will submit this new information to fulfill the data requirements for OPPTS Guidelines 850.1025, 850.1035, 850.1045, and 850.1055 for estuarine/marine invertebrate species.”

EFED Response: EFED will review any open literature data submitted to fulfill the data requirements for any effects endpoint when data are received. EFED requests that SePro submit studies, along with raw data, proposed to fulfill OPPTS Guideline 850.1025, 850.1035, 850.1045, and 850.1055.

27. Comment: Page 24 states, “The data request from the Agency for a whole sediment chronic freshwater invertebrate study is not supported by the data on file with EPA. As per 40 CFR 158, whole sediment chronic toxicity data for fr eshwater invertebrates are required if: EEC > 0.1 of acute LC50 (48-hr midge data) AND t1/2 > 10 days AND Log Kow > 3 OR Koc >1000 L/kg

Fluridone satisfies only the first two of these requirements, but not the third: EEC = 0.15 mg/L (max application rate) > 0.13 mg/L (0.1 * LC50) t1/2 by aqueous photolysis = 33 days Log Kow = 1.97 Koc = 260-740

Koc values cited within the BLM 2005 document a ppear to have been derived using Stockton clay or other such artificial sediments with hi gh clay content. Such st udies would provide an inappropriate model of fluridone fate in natural sediment systems, and are likely to provide inaccurate Koc values. Additionally, the following spiked-sediment study conducted with

Chironomus tentans (now C. dilutus ) larvae indicates that the compound is of very low toxicity.”

EFED Response: Data are needed for freshwater inve rtebrates because aerobic aquatic halflives of fluridone (MRID 44154801) are greater than 10 days and some K OC values are ≥ 1000 L/kg (BLM 2005). Most reported K OC values ranged from 270-6400 (BLM 2005). This wide range in measured K OC values is consistent with what is expected to occur in the natural environment (Allen-King et al. , 2002). Finally, the EEC of 0.150 mg/L is > 0.1 x 1.3 mg/L (an acute LC50 for midge; MRID 00103297). Therefore, w hole sediment chronic toxicity testing is

recommended. It is recomme nded that SePro submit a draft protocol of the study before beginning the study.Page 25 of 26 27. Comment: Page 25 states, “SePRO has identified public literature that is available to address terrestrial plant studies data requireme nts and will submit this information to EPA to

review.”

EFED Response: EFED will review any open literature data submitted to fulfill the data requirements for any effects endpoint when data are received. EFED requests that SePro submit studies, along with raw data, proposed to fulfill OPPTS Guideline 850.4100 and 850.4150.

28. Comment: Page 26-27 discuss why SePro beli eve that OPPTS Guidelines 850.4400 and 850.5400 are not needed for the ecological risk assessment and summarize open literature data that have the potential to fulfill these data requirements.

EFED Response: Tier II Aquatic Plant growth (algal and aquatic vascul ar plant toxicity)

Guideline 850.4400 and 850.5400 are recommended fo r all known phytotoxicants (see 40 CFR Part 158.660 Table - Nontarget Pl ant Protection Data Requireme nts and Footnote 4). EFED understands that Fluridone is expected to have effects on vascular plan ts and risk will be predicted for aquatic vascular plants. Additiona lly, EFED is aware that there are currently no listed algae or diatoms. For a complete ecologica l risk assessment, an analysis of how far from the use site risk to aquatic plants will occur is conducted. In order to c onduct this analysis it

must be known at what concentrations effects to aquatic plants will occur. This information will be used to assess the potential for direct and indirect effects to both nonlisted and listed species. Therefore, these data requirements are still re commended as needed for the ecological risk

assessment.

29. Comment: Page 31 states, “EPA issued an a ddendum (dated September 2, 2009) to the DERs for several ecotoxicology studies c onducted on fluridone, which downgraded the studies to unacceptable or supplemental. As previously noted, SePRO has reviewed the addenda in detail and the applicable study repor ts and will submit an official response to EPA’s DER (outside of the public docket comm ent period) rebutting many of the changes to the classification of the data. This response w ill be submitted directly to EPA and not to the public docket as it contains specific information related to the conduct of the studies that may

be considered confidential business information.”

EFED Response: EFED believes that the DER recl assifications were necessary and appropriate. Many of the reasons for the specific reclassifications were discussed previously under specific data requirements in this documen t. EFED will review any additional information

submitted on these studies when the information is submitted.

Literature Cited

Allen-King, R. M., Grathwohl, P., & Ball, W. P. 2002. New modeling para digms for the sorption of hydrophobic organic chemicals to hetero genous carbonaceous matter in soils, sediments, and rocks. Advances in Water Resources, 25 , 985-1016. Riley, F., & Finlayson, S. 2004. Acute Toxicities of Herbicides Used to Control Water Hyacinth
and Brazilian Elodea on Larval Delt a Smelt and Sacramento Splittail. Administrative Report 04-003. June 8, 2004. Office of Spill Prevention and Response. Available atPage 26 of 26 http://www.cdpr.ca.gov/docs/emon/surfwtr/hazasm/hazasm04_03.pdf (Accessed February 8, 2010).

USEPA. 2004. Human Health Risk Assessment for Fl uridone TRED. PC Code 112900. DP

Barcode D306456 . August 17, 2004. Health Effects Division, Office of Pesticide Programs. United States Environmen tal Protection Agency. Available at http://www.fluoridealert.org/pe sticides/fluridone.hrs.aug.2004.pdf (Accessed February 8, 2010).

USEPA. 2009. Initial Risk-Based Priori tization of High Production Vo lume (HPV) Chemicals: N-methylformamide (CASRN 123-39-7) (CA Index Name: Formamide, N-methyl) Supporting Chemical: N,N-dimethylformamid e (CASRN 68-12-2) (CA Index Name: Formamide, N,N'-dimethyl-) . April 2009. United States Environmental Protection Agency. Risk-Based Prioritization Document. Available at http://www.epa.gov/hpvis/rbp/123-39 -7_Methylformamide_Web_April%202009.pdf (Accessed February 8, 2010).