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 regarding attributes of the parent compound and its 

transformation products. It describes the preliminary ecological risk hypothesis and the 

processes that will be used during the completion of drinking water and ecological risk 

assessments in support of registration. This document also recommends studies that should be 

included in a data call-in (DCI) to address uncertainties surrounding potential ecological effects 

(DP Barcode D362249) of fluridone. 

In addition to the changes in response to comments, 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 representing 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 estuarine environments, indigenous listed and unlisted species 

and habitat. Evaluations of the pesticide in such environments should be of sufficiently 

broad scope to provide substantive understanding 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 and listed species will be considered 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 bioaccumulation occurs in mammals, mollusks, invertebrates 

and other marine organisms? 

The point of application in the subject complaint was Lake Rousseau, a lake with substantial 

surface vegetation cover and naturally shaded at depth due to high tanin content in the water. 

The Lower Withlacoochee River is largely shaded by shoreline trees. Such circumstances 

interfere with photolysis and associated degradation and are not thought unique to this 

system. It is not clear such considerations have been fully evaluated by previous 

registrations processes or regulated by label restrictions. Such 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, and to determine the extent of pesticide residues 
Page 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-water partition coefficient (log KOW=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 assessments (Registration Review: Preliminary 

Problem Formulation for Ecological Risk, Environmental Fate, 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 degree 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 mixed 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 not 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 resident to the water bodies discussed 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 degradates. Page 20 of the Problem Formulation 

indicates this when it states, “For uses in coastal areas, aquatic habitat 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 bodies. 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 structure 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 effects. 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 vertebrates and invertebrates are available to assess 

risk to estuarine/marine organisms (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 Conservation Commission (FWCC) effective July 

2008. The FWCC is proscribed by state statute from engaging in any activity related to 

water quality analysis or enforcement. FWCC does not perform toxicological screens of fish 

or other aquatic organisms during die off events. We find this circumstance disconcerting to 

say the least, and question the state’s oversight process in aquatic 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, there is no basis for defending application of 

the subject pesticide in tidewater or brackish 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 indirect impacts to listed species. We do not see a practical 

difference between point of “application” versus “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, Inc., a registrant of fluridone 

(EPA-HQ-OPP-0160-0026) 

1. Comment: Page 2, Comment 1a states “Fluridone Summary Document (EPA-HQ-OPP2009-0160-0002), page 5: Data appear to be required 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 states that although data are needed, “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 promulgated to the Final Work Plan and subsequent 

Data Call-In.”

EFED Response: The fish early-life stage study for 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 Terrestrial and Aquatic Nontarget organism Data 
Page 5 of 26 

Requirements Table). The reason that data are needed for the same species is so that an acute-tochronic ratio may be calculated and used to estimate chronic toxicity endpoints to more sensitive 

species. Acute-to-chronic ratios may be calculated using either data from a fish early life stage 

study or a fish full life cycle study. An acceptable fish full-life cycle study is available for the 

fathead minnow (MRID 00103309). Also, acute data 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 Rainbow trout and Channel catfish indicate that the 

EP tested did not influence the toxicity of fluridone. In the absence of an acute study on the 

TGAI, the 96-hr LC50 for the EP for the Fathead minnow would be used to estimate an ACR. 

The estimated ACR is 17.3 based on a 96-hr LC50 of 8.3 mg a.i./L for the EP (MRID 00103297). 

Additionally, the weight of evidence does not indicate 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-Observable-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 this 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, freshwater 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 Preliminary 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) will either demonstrate that existing fathead minnow acute 

toxicity data are acceptable 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 Guideline 850.1400) or full life-cycle 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, 850.1300, aquatic invertebrate life 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 for 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 the test material but it is implied that data 

on the TGAI, not TEP, would be required. KTI requests that the Agency confirm that data on 

TGAI only are required for aquatic invertebrate 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, “Preliminary 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 over time. None of these studies ever detected 

residues of NMF.” 

EFED Response: EFED asks the registrant to submit any publications in which fluridone and Nmethyl formamide (NMF) levels in water after treatment are monitored over time. Note that the 

limit of quantitation should be low enough to detect the concentration of NMF at expected 

concentrations. If the LOQ and limit of detection (LOD) are too high to detect 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 aspects of pesticide transport when determining where and when 

samples are collected. Additionally, monitoring should be conducted from use-specific sites 

relevant to the pesticide registration. Finally, the analytical sampling 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 requirement 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 controlled, partially controlled or not controlled. 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 WhiteCap label specifies that fluridone 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 endangered or threatened species and results from 

testing fluridone against such organisms would not yield data that would be useful in risk 

assessments or mitigation strategies.” 

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

OPPTS Guideline 850.4400 and 850.5400 are recommended for all known phytotoxicants (see 

40 CFR Part 158.660 Table - Nontarget Plant Protection Data Requirements and Footnote 4). 

EFED understands that fluridone is expected to have effects on vascular plants and risk will be 

predicted for aquatic vascular plants. Additionally, EFED is aware that there are currently no 

listed algae or diatoms. For a complete ecological risk assessment, an analysis of how far from 

the use site risk to aquatic plants will occur is conducted. In order to conduct 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 request for acute toxicity to 

freshwater invertebrates (OPPTS 850.1010), “In the Preliminary Problem Document, Table 

D1 in Appendix B lists a number 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. Data with other species also yielded similar 

results. Because there are several studies that provide similar results, despite possible 

deficiencies, KTI does not believe that additional studies would yield new information.” 

EFED Response: Freshwater invertebrate acute toxicity data for Daphnia (MRID 000103297) 

were fully reviewed since the publication of the problem formulation and found to be acceptable. 

EFED needs to be able to evaluate potential exposure to current formulations of fluridone. 

EFED requests that the registrants provide EFED with information on whether the studies 

completed with the previous end products are representative of current products on the market. 

If they are not representative, studies examining toxicity of current end use products that are 

representative of current TEPs are still needed. More information 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 request 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 technical material and two studies with TEP. The 

reported EC50 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; EC50 values were not reported in the remaining two studies. The data from 

these four studies should be sufficient, despite 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 eastern 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 effects concentration (EC50) 

and it is not known at what exposure 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 concentrations cannot be 

determined with the available information. 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 would be observed at higher 

treatment levels. Additionally, precipitation was observed in stock solutions and fluridone was 

not detected in some samples. This study is not useful in determining whether the formulation 
Page 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. Therefore, a study examining the toxicity of a 

representative TEP on oysters (OPPTS Guideline 850.1025) is needed. 

Finally, effects endpoints are needed 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 studies 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 concentration of fluridone in aquatic habitat), the data should be 

sufficient to conduct the appropriate risk assessments.” 

EFED Response: Two studies were submitted examining toxicity to sheepshead minnow, 

MRIDs 00108837 and 00103316. In MRID 108837, acute toxicity of TGAI was examined. 

Two treatment levels exceeded solubility and concentrations were not measured in filtered or 

centrifuged samples. The dissolved 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 water or in centrifuged water. The test results do 

show that sublethal effects and mortality may occur with exposure to fluridone. In order to 

examine risk to estuarine/marine fish, an acceptable study examining acute toxicity of TGAI 

fluridone (OPPTS Guideline 850.1075) to estuarine/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 combined. Therefore, the concentration over time is 

not known. Not enough information is available from this test to determine a reliable toxicity 

endpoint. In order to examine risk to estuarine/marine fish from 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 data 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 for rainbow trout, channel catfish, bluegill, 

and fathead minnow with TGAI and TEP (MRID 000103297) were fully reviewed since the 

publication of the problem formulation. Studies conducted for rainbow trout (coldwater species) 

and channel catfish (warmwater species) with TGAI are acceptable. Additionally, studies 

examining toxicity to formulations are acceptable for Rainbow trout and Fathead minnow. 
Page 9 of 26 

Therefore, at this time we do not recommended a data call in for 850.1075 with TGAI for 

fluridone. The problem formulation was revised 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 recommends that the registrant provide information on 

whether studies examining toxicity to EPs are applicable 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 should be conducted with a species that also have 

TGAI data available. Without these data it is not known if the formulation results in greater 

toxicity than the active ingredient 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 file 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 studies 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 actual or simulated field testing data are 

required/submitted. Actual or simulated field testing 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 acknowledges 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 validated 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 laboratory photolysis studies at up to 74% of 

the applied amount of fluridone. NMF did not degrade 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 photodegradate of fluridone, NMF is on the TSCA inventory 

and is considered a high production volume (HPV) chemical with an estimated 1 to 10 
Page 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 electronics 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 effects that can likely be used to satisfy the data gaps 

identified in the fluridone registration review.” 

EFED Response: The registrant should submit the specific studies and raw data that are 

proposed to fulfill the data gaps for NMF. EFED 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 water and 36% in lake water. NMF is relatively stable to 

hydrolysis and photooxidation, but is readily biodegradable 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 presence 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 Florida 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 and 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 fluridone was applied to each pond to achieve a 

fluridone concentration of 150 ppb. Over 167 days, 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 taken 324 days after treatment did not contain 

any residues of NMF at a detection limit of 0.005 ppm. 

Fluridone was applied to two ponds in New England 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 detected 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 fluridone, resulting in virtually no exposure of 

NMF to nontarget species. 

Irrespective of the biodegradation 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 μg/L), and well below levels of toxicity demonstrated in 

the laboratory as discussed below. Indeed, in EPA’s 2004 drinking water assessment, the 
Page 11 of 26 

estimated peak acute and chronic exposure to NMF was 2.64 μg/L and 1.45 μg/L, 

respectively, based on an application rate to drinking water systems of 20 ppb [U.S. EPA, 

2004]. 

Since fluridone applications are made directly to water, the exposure of fluridone to 

terrestrial matrices, such as birds, 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 water, not on soil. Birds consuming 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 fluridone testing. Nearly all of the ecotoxicology 

tests require exposure to light. As such, fluridone would naturally degrade to NMF during 

these studies and result in inadvertent exposure to NMF, meaning data developed for 

fluridone would support the NMF requirements for fluridone registration review.” 

EFED Response: EFED would not expect NMF to be present at the limit of detection of 2 ppm 

with 150 ppb concentrations of fluridone. Monitoring data should have a limit of detection that 

can detect NMF at concentrations that are expected to be present in the environment and that 

may be of a risk concern. 

Birds may be exposed in the terrestrial environment to NMF and fluridone. Fluridone may occur 

in the terrestrial environment in water and thus photodegradation in water may occur in the 

terrestrial environment. Finally, 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 for 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 ecological effects data for NMF and DMF. 

EFED Response: The registrant should either submit data (along with the raw data) or clearly 

identify what HPV data they would like the Agency to use to fulfill the data requirement for 

NMF. EFED will review the identified data for potential use in the evaluation of risk from 

exposure to NMF. At this time, EFED does not consider data on DMF to be a suitable surrogate 
Page 12 of 26 

for NMF. The data requirements for the HPV 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 photodegradate 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 photodegradation (90% after 140 minutes), readily 

biodegrades (> 90% after 28 days) under both aerobic and anaerobic 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 degradation properties as 

benzoic acid. 

Irrespective of the biodegradation of 3‐TFMBA, the fluridone application rates (and thus, 

potential aquatic exposure to 3‐TFMBA) are low: the maximum single and combined 

application rate to water is 150 ppb. Even conservatively 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 fluridone is applied directly to water, and 

photodegradation of fluridone to 3‐TFMBA on terrestrial matrices is not expected.” 

EFED Response: EFED believes that the chemistry 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 this 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 gaps are summarized below:” The registrant 

indicates that studies on acute oral avian toxicity and avian reproduction are not needed 

because it is unlikely that birds will be exposed to this degradate. 

EFED response: EFED believes that birds may be exposed 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) waterfowl swim, feed, and drink water that may be 

treated with fluridone. Fate data on 3-TFMBA are not available for EFED to understand its 

environmental fate and discount potential exposure. 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 information when the ecological risk assessment 

is completed. The information provided is specific to one label. When EFED performs the risk 

assessment, parameters on all labels will be evaluated. As there are no restrictions on the labels 

on reapplication intervals or number of applications per year, a conservative assumption that 

results in a reasonable chronic maximum exposure estimate to fluridone will be made to estimate 

exposure. For the geographic restrictions for states and U.S. territories, it will be assumed that 

fluridone may be used in all states and U.S. territories unless the label specifically 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 manufacturer 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 Work Plan and subsequent Data Call-In.”

EFED Response: Data on the TEP are not required for OPPTS Guideline 850.1300. This typo 

is corrected in the revised problem formulation. 

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

The Summary Document states this study is required; however, it is not listed as required 

anywhere in the Preliminary Problem Formulation Document and no justification for the 

requirement of the study is identified. We believe the data requirement listing is in error and 

should not be promulgated to the Final Work Plan and subsequent Data Call-In.” 

EFED Response: The fish early-life stage study for 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 Terrestrial and Aquatic Nontarget organism Data 

Requirements Table). The reason that data are needed for the same species is so that an acute-tochronic ratio may be calculated and used to estimate chronic toxicity endpoints to more sensitive 

species. Acute-to-chronic ratios may be calculated using either data from a fish early life stage 

study or a fish full life cycle study. An acceptable fish full-life cycle study is available for the 

fathead minnow (MRID 00103309). Also, acute data 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 Rainbow trout and Channel catfish indicate that the 

EP tested did not influence the toxicity of fluridone. In the absence of an acute study on the 

TGAI, the 96-hr LC50 for the EP for the Fathead minnow would be used to estimate an ACR. 

The estimated ACR is 17.3 based on a 96-hr LC50 of 8.3 mg a.i./L for the EP (MRID 00103297). 

Additionally, the weight of evidence does not indicate a need for additional chronic data on fish. 

Both the Chinook salmon early life stage study (MRID 45915601) and Fathead minnow full-life 
Page 14 of 26 

cycle study (MRID 00103309) have similar No-Observable-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 this 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, Freshwater Fish Life Cycle (TGAI) – 

SePRO requests that EPA classify this data requirement as “Reserved”. Acceptable fish life 

cycle data are available with 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 Guideline 850.1400) or full life-cycle 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 believes that, when the body of literature concerning fluridone 

dissipation and degradation is considered, 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 need 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. Therefore, 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 majority of UV-B radiation is 

filtered/adsorbed by the DOC that is present 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 slower than represented in 

Saunders and Mosier (1983). In fact, the half-life of fluridone observed and 

measured in a field study incorporating 40 fluridone-treated ponds and lakes 

averaged 20 days and resulted from not only photolysis, but also from dissipation 

and dilution into untreated waters and adsorption onto plants (West et al., 1983).” 
Page 15 of 26 

EFED Response: EFED recognizes that the rate of photolysis of fluridone in the field will 

depend on exposure to sunlight. Indeed, field dissipation half-lives are discussed under Section 

3.3.1.c Aquatic Field Dissipation of the problem formulation. 

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

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

2005).” 

EFED Response: EFED will review the Zahn-Wellens biodegradation 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 NMF 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 formed. Similarly, 3-TFMBA is calculated to 

form at a rate of 0.0044 day-1, but biodegrades at a rate of 0.018 day-1, about four 

times (4x) faster than formation. Even 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 the Agency. With regard to the referenced 

monitoring data from the state of Michigan, 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 days post initial treatment. 

4. Sample all sites at 60 days post initial treatment. 

Based on the fate properties of fluridone, and its fast photolysis degradation 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 3CF3- Benzoic acid), were not included in such sampling protocol. 

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

• Freshwater Invertebrate Acute Toxicity (OPPTS Guideline 850.1010); 
Page 16 of 26 

• Acute Toxicity Freshwater Fish: Coldwater and Warmwater Species (OPPTS Guideline 

850.1075); 

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

• Freshwater Fish Early-Life Stage and Estuarine/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 necessary to evaluate risk to organisms due 

to exposure to NMF. The problem formulation 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 exposure 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 aquatic 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 effects with exposure to NMF will occur 

without a full exposure assessment and data examining at what concentrations effects are likely 

to occur. EFED will evaluate this when data are submitted to the Agency. 

b. Comment: Page 6 states, “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 water, not on soil. Birds consuming water 

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

since the maximum fluridone concentration would be 150 ppb which could 

hypothetically result in a maximum potential NMF level of <27 ppb. However, as 

noted above, SePRO does not believe there will be any chance for potential 

exposure to NMF as the degradation rate exceeds the formation rate.” 

EFED Response: EFED cannot evaluate whether effects with exposure to NMF will occur 

without a full exposure assessment and data examining at what concentrations effects are likely 

to occur. EFED will evaluate this when data are submitted to the Agency and when the 

ecological risk assessment is performed. 

8. Comment: Page 7 states, “Available studies were conducted with NMF and/or dimethyl 

formamide (DMF), considered under the HPV program to be a suitable surrogate for NMF 

(US EPA 2009b)” Additionally, SePRo identifies acute and chronic 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 pesticide 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 are 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 other selected sources. These 

screening-level characterizations do not constitute full risk assessments. 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 categories” (USEPA, 2009). The decision only applies to the HPV 

Challenge Program and the ChAMP program. Additionally, the document also states that the 

decisions are based on an assumption of low likelihood of exposure because NMF is mainly used 

as an intermediate. For example, Page 1 states, “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 determinations are not applicable to degradates of pesticides and 

risk assessments conducted on degradates of pesticides 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 consider 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 identified 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 potential 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 chemistry 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 the potential for exposure to 3-TFMBA is low due to the 

low application rate of fluridone in water and the effects endpoints and terrestrial exposure is 

not expected because fluridone is applied directly to water and photodegradation of fluridone 

to 3-TFMBA on terrestrial matrices is not anticipated. 
Page 18 of 26 

EFED Response: Degradation of fluridone is also likely to occur in the terrestrial 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, chronic data are not needed. 

EFED response: EFED believes that the chemistry 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 fluridone use indicate that fluridone should be held 

at a concentration of 150 ppb for 30 to 90 days and does not have any reapplication restrictions. 

It could be applied at 150 ppb to a water body throughout the year. This would result in chronic 

exposure to fluridone and its degradates despite the rates of degradation 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 consistent 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 already been exposed to NMF through testing, as 

nearly all of the ecotoxicology tests require exposure to light. As such, fluridone would 

naturally degrade to NMF during these studies and result in inadvertent exposure to NMF, 

meaning data developed for fluridone would 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 fluridone; however, it is not known at what concentrations and how 

consistent that exposure was overtime. Therefore, the available data cannot be used to evaluate 

the risk of potential exposure to NMF. 

14. Comment: Page 10 states, “EPA stated that the 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 there 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 any 
Page 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 anticipated; 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 method 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, channel catfish, bluegill, 

and fathead minnow with TGAI and TEP (MRID 000103297) were fully reviewed since the 

publication of the problem formulation. Studies conducted for rainbow trout (coldwater species) 

and channel catfish (warmwater species) with TGAI are acceptable. Additionally, studies 

examining toxicity to formulations are acceptable for Rainbow trout and Fathead minnow. 

Therefore, at this time we do not recommended a data call in for 850.1075 with TGAI for 

fluridone. The problem formulation was revised 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 recommends that the registrant provide information on 

whether studies examining toxicity to EPs are applicable 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 should be conducted with a species that also have 

TGAI data available. Without these data it is not known if the formulation results in greater 

toxicity than the active ingredient alone. More information on data requirements for TEPs was 

added to Page 40 of the problem formulation. 

16. Comment: Page 17 states, “Bluegill acute study (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 requirement. 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 the 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 reported, the three highest concentrations tested 

exceed the solubility of fluridone in distilled water (12.3 mg/L) (USEPA, 2004). Because the 

fluridone concentrations were higher than solubility and the measured concentrations 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, this has always been a 

standard requirement in aquatic toxicity guidelines. The study still has valuable information and 

is considered supplemental. Mortalities occurred at nominal concentrations of 12.5 and greater. 

As fluridone degrades rapidly via aqueous photolysis (aqueous photolysis half-life ranged from 

0.9-2.4 days; MRID 00103326) measured concentrations in acute tests are needed to verify that 

exposure was constant over time. All of these variables taken together indicate that the exposure 

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

assessment. 

17. Comment: “Salmon early life stage study (850.1400) [MRID 46112001] – EPA listed this 

study as an acute toxicity study (850.1075); however, it is actually 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 concentration 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 directly testing 96 hr survival 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 toxicity study on Chinook salmon and a 

seawater adaptability test. In the acute toxicity study (MRID 46112001) an acute endpoint was 

not available, e.g., 96-hr LC50>5.76 mg/L; therefore, this study may not be used to fulfill the 

acute toxicity to coldwater fish (OPPTS Guideline 850.1075). However, studies are available 

on the Rainbow trout and Channel Catfish. EFED 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 using the TEP for the rainbow trout, fathead 

minnow, and bluegill. 

EFED Response: Data are needed that are representative of current TEPs. The registrant 

should provide information indicating whether studies examining toxicity to EPs are applicable 

to current products or submit studies examining exposure to current 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 reported 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 reviewing EPA’s memorandum dated 

September 2, 2009 and will provide a detailed response 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 fluridone was tested at nominal 

concentrations of 0.0 (control), 0.0 (solvent control 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 concentration in water or exposure 

concentration cannot be determined because concentrations 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 are therefore determined to be supplemental. 

Sublethal effects and mortality may occur at concentrations 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 precipitate and the test concentrations exceeding 

solubility the true exposure concentration is not known. Nominal concentrations ranged from 3-

50 mg/L. Mortality was observed at 12 mg/L and above. Water was filtered prior to analysis. 

Measured concentrations ranged from 44-93% of nominal. 

EFED considers both of these studies to be supplemental and will use the data 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 study (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 requests 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 been 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 entirety 
Page 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 publication of the problem formulation and found to be acceptable. 

EFED needs to be able to evaluate potential exposure to current formulations of fluridone. 

EFED requests that the registrants provide EFED with information on whether the studies 

completed with the previous end products are representative of current products on the market. 

If they are not representative, studies examining toxicity of current EPs that are representative of 

current TEPs are still needed. More information 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 toxicity studies conducted on Daphnia magna did not have 

measured concentrations available for the tests because the samples were 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 study 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 acute toxicity studies (850.1055) 

[MRIDs 00103311 and 00103315] – 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 

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 fluridone was tested at nominal 

concentrations of 0.0 (control), 0.0 (solvent control with 0.9 mL dimethylformamide in 1-L 

seawater), 6.0, 10.0, 32.0, 56.0, 100.0, and 320.0 mg/L. Water 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 filtering (Schleicher and 

Schuell analytical filter paper, 12.5 cm, pore size not specified). Measured concentrations were 

9-105% of nominal with the lowest recovery observed at the highest test concentrations. Actual 

exposure concentrations cannot be determined because of the uncertainty in the measured 

fluridone concentrations. The factors contributing to this uncertainty 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 the 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. Therefore, the study 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). 

MRID 103315 was determined to be supplemental when it was initially reviewed in 1982. The 

original DER states that the study could not be used to fulfill the guideline requirement for acute 

toxicity test using the formulated product on the embryo-larvae of an oyster species. The DER 

states, “Because solubility problems and/or possible losses of test material from aeration, 

exposure from the formulated product cannot be quantified.” Additionally, three of the nominal 

test concentrations were above the solubility of fluridone. This leaves only three treatment levels 

below the level of solubility. Therefore, the study 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). EFED 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 requirement.” Additionally, SePro indicates that 

treatment levels in these studies were 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 the study is not available. The highest tested 

measured concentration was 1.4 mg/L. This study should be repeated at higher exposure 

concentrations. None of the treatment levels were above the solubility (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 samples and measured concentrations were highly 

variable. For example, at the 1 mg/L treatment level the first measured concentration showed 

0.08 mg/L and the second measured concentration 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 solubility (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 acceptable, 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 available 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 freshwater 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 appear to have been derived using Stockton 

clay or other such artificial sediments with high clay content. Such studies 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 invertebrates because aerobic aquatic halflives of fluridone (MRID 44154801) are greater than 10 days and some KOC values are ≥ 1000 

L/kg (BLM 2005). Most reported KOC values ranged from 270-6400 (BLM 2005). This wide 

range in measured KOC 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, whole sediment chronic toxicity testing is 

recommended. It is recommended 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 requirements 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 believe 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 vascular plant toxicity) 

Guideline 850.4400 and 850.5400 are recommended for all known phytotoxicants (see 40 CFR 

Part 158.660 Table - Nontarget Plant Protection Data Requirements and Footnote 4). EFED 

understands that Fluridone is expected to have effects on vascular plants and risk will be 

predicted for aquatic vascular plants. Additionally, EFED is aware that there are currently no 

listed algae or diatoms. For a complete ecological risk assessment, an analysis of how far from 

the use site risk to aquatic plants will occur is conducted. In order to conduct 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 recommended as needed for the ecological risk 

assessment. 

29. Comment: Page 31 states, “EPA issued an addendum (dated September 2, 2009) to the 

DERs for several ecotoxicology studies conducted on fluridone, which downgraded the 

studies to unacceptable or supplemental. As previously noted, SePRO has reviewed the 

addenda in detail and the applicable study reports and will submit an official response to 

EPA’s DER (outside of the public docket comment period) rebutting many of the changes to 

the classification of the data. This response will 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 reclassifications were necessary and 

appropriate. Many of the reasons for the specific reclassifications were discussed previously 

under specific data requirements in this document. 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 paradigms for the sorption 

of hydrophobic organic chemicals to heterogenous 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 Delta Smelt and Sacramento Splittail. Administrative 

Report 04-003. June 8, 2004. Office of Spill Prevention and Response. Available at 
Page 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 Fluridone TRED. PC Code 112900. DP 

Barcode D306456. August 17, 2004. Health Effects Division, Office of Pesticide 

Programs. United States Environmental Protection Agency. Available at 

http://www.fluoridealert.org/pesticides/fluridone.hrs.aug.2004.pdf (Accessed February 8, 

2010). 

USEPA. 2009. Initial Risk-Based Prioritization of High Production Volume (HPV) Chemicals: 

N-methylformamide (CASRN 123-39-7) (CA Index Name: Formamide, N-methyl) 

Supporting Chemical: N,N-dimethylformamide (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).