OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

April 9, 2015

PC Codes: 122805 & 122809

MEMORANDUM DP Barcode: D425772

SUBJECT: EFED Response to Registrant Comments Regarding the Registration Review Problem 

Formulation for Fluazifop-p-butyl

FROM: N.E. Federoff, Wildlife Biologist

Environmental Risk Branch 2

Environmental Fate and Effects Division (7507P)

THRU: Brian Anderson, Chief

Environmental Risk Branch 2

Environmental Fate and Effects Division (7507P)

TO: Matthew Manupella, CRM

 Pesticide Re-Evaluation Division (7508P)

The Environmental Fate and Effects Division (EFED) has completed the responses to the 

Registrant (Syngenta Crop Corporation LLC) comments regarding the preliminary problem 

formulation of fluazifop-p-butyl. 

EPA statement

Reference (Page 3, 

Bullet 2)

No data have been submitted regarding chronic toxicity to 

estuarine/marine fish or invertebrates.

Syngenta Comment: Syngenta previously submitted a chronic mysid study on the parent

compound (MRID 00093805). Syngenta respectfully will provide a courtesy copy of the original 

study report in a separate submission.

EPA Response: EFED agrees this study was submitted (MRID 00093805). The study was done 

using Fluazifop-butyl (122805). It was listed as supplemental and non-repairable. The NOAEC 

for this study would be 15 ppb. This study needs to be repeated using fluazifop-p-butyl

(122809).

EPA statement

Page 14, Table 1,

Fluazifop-p-acid

Henry’s Law Constant

Syngenta Comment: Syngenta will respectfully submit additional data for this data gap by the 

end of 1st Quarter 2015.

EPA Response: EFED will review the data once submitted.
EPA statement

Reference (Page 29, 

Paragraph 5)

An ACR value was obtained from the freshwater animal studies and 

applied to the acute toxicity data for estuarine/marine species to 

estimate chronic toxicity values for these species. This approach

yielded a NOAEC value of 3.10 mg ai/L for the estuarine/marine fish

C. variegatus.

Syngenta Comment: Syngenta agrees that an ACR is a useful technique for calculating

chronic effects values for marine fish.

EPA Response: EFED would rather use actual test data, but if none are available, EFED 

agrees that ACR values can be used.

EPA statement

Reference (Page 30, 

Paragraph 1, Line 4)

Fluazifop-p-butyl is slightly toxic to the honey bee with an acute 

contact LD50 of 63 μg/bee

Syngenta Comment: Syngenta notes that the acute contact toxicity study (MRID 00162453)

cited in the Preliminary Problem Formulation (PPF) resulted in LD50 > 200 μg/bee,

indicating that fluazifop-P-butyl is practically non-toxic to honey bees.

EPA Response: The DER in question (252825) was an acceptable study resulting in oral 

LD50s of >200 ug/bee for technical grade and 63 ug/bee for formulation. Results for acute 

contact were LD50s of >200 ug/bee for technical grade and >100 ug/bee for formulation. The 

most toxic value was listed but should have said for oral and not contact. 

EPA statement

Reference (Page 31, 

Table 9)

Referenced endpoint for aquatic non-vascular studies is presented as 

biomass.

Syngenta Comment: Syngenta respectfully states that effective concentrations (ECx)

calculated based on growth rate are considered more robust than those based on standing crop 

(cell density and biomass) for a given time-point since growth rate is independent of exposure 

time (EPA 2012). For aquatic plants, study duration, conditions of temperature, light, and 

nutrients, and reported endpoints can vary considerably among studies. Other resource limiting 

factors, such as nutrient depletion and self-shading, can complicate the interpretation of

reported plant ECxs. These factors may affect study results, which could result in biased 

estimates in certain cases for some species (EPA2012). Using absolute biomass can potentially

result in particularly misleading ECx’s when growth rates are modest, and a departure from

exponential growth will be most pronounced in the treatments with the highest growth 

rates (EPA 2012). With respect to toxicity testing, differences in design of the study can 

result in complicated growth dynamics and relationships that are difficult to interpret and 

apply (EPA

2012).

As indicated by Bergtold and Dohmen (2011), the Organization for Economic Cooperation and 

Development (OECD) indicates a clear preference for growth rate as the appropriate endpoint

in the lemna and algal toxicity test guideline (OECD 2006a,b). Specifically, the OECD

guideline for testing growth inhibition in freshwater alga and cyanobacteria (OECD 2006a)

states:

Page 2 of 6
“ECx values based upon average specific growth rate (ErCx) will generally be 

higher than results based upon yield (EyCx) if the test conditions of this

Guideline are adhered to, due to the mathematical basis of the respective 

approaches. This should not be interpreted as a difference in sensitivity between 

the two response variables, simply that the values are different mathematically. 

The concept of average specific growth rate is based on the general exponential 

growth pattern of algae in non-limited cultures, where toxicity is estimated on

the basis of the effects on the growth rate, without being dependent on the

absolute level of the specific growth rate of the control, slope of the

concentration-response curve or on test duration. In contrast, results based upon

the yield response variable are dependent upon all these other variables. [Yield]

is dependent on the specific growth rate of the algal species used in each test

and on the maximum specific growth rate that can vary between species and

even different algal strains. This response variable should not be used for 

comparing the sensitivity to toxicants among algal species or even different 

strains.”

Based on the aforementioned information, relative growth rate is the most appropriate

aquatic plant endpoint for ecological risk assessment.

Bergtold, M. and G.P. Dohmen. 2011. Biomass or growth rate endpoint for

algae and aquatic plants: Relevance for the aquatic risk assessment of

herbicides. Integr. Environ. Assess. Manag. 7: 237-247.

OECD (Organization for Economic Cooperation and Development). 2006a. 

OECD Guideline 201: Freshwater alga and cyanobacteria, growth inhibition 

test. Adopted 23 March 2006. Paris.

OECD (Organization for Economic Cooperation and Development). 2006b. 

OECD Guideline 221: Lemna sp. growth inhibition test. Adopted 23 March

2006. Paris.

US EPA, 2012. Proposed Methodology for Specifying Atrazine Levels of

Concern for Protection of Plant Communities in Freshwater Ecosystems. Report 

To: Environmental Fate and Effects Division, Office of Pesticide Programs, 

U.S. Environmental Protection Agency, Washington, DC. EPA/600/R-12/019. 

Mid- Continent Ecology Division, National Health and Ecological Effects

Laboratory, Office of Research and Development, U.S. Environmental 

Protection Agency, Duluth, MN. March 5, 2012.

EPA Response: EFED’s current approach is to use the most sensitive endpoint available to 

assess risk to terrestrial and aquatic organisms. For plants, both biomass as well as growth are 

possible endpoint parameters. 

EPA statement

Reference (Page 31, 

Table 10)

Sub-acute dietary LC50 = 4141.5 ppm, (MRID 00087481, 1987

Syngenta Comment: Syngenta respectfully submits that the endpoint for MRID 00087481 is >

21348 ppm ae (25000 ppm ai) rather than the cited 4141.5 ppm ae.

Page 3 of 6
EPA Response: This study (MRID 00087481, 1980) is supplemental and did not meet 

guideline requirements. The ducks rejected food at all dose levels for the first 2 days of the 

study and at all doses but the lowest two treatment levels for the remainder of the test. The 

25,000 ppm ai endpoint was from the 1980 supplemental study with Fluazifop butyl. The 

cited data were for Fluazifop-p-butyl (MRID 41199201, 1987), although the LC50 endpoint 

should have been listed as being >4850 ppm ai). 

EPA statement

Reference (Page 32,

Table 10)

Insects, honeybee acute contact, 48 hr LD50=63 μg/bee (MRID

00162453)

Syngenta Comment: Syngenta submits that the 48 hr contact LD50 for MRID 00162453 is

> 200 μg fluazifop-P-butyl/bee.

EPA Response: As mentioned previously, the LD50 of 63 ug/bee was the most toxic value 

but was for the toxicity of the oral exposure study. The acute contact LD50 was >200 ug/bee

for the technical grade.

EPA Statement

Page 35 8. Endangered Species Assessment

Syngenta Comment: A summary of the types of higher-tier data and assessment refinements

available to more accurately and realistically evaluate potential risks to endangered species is 

provided in MRID 49200601.

EPA Response: EFED will take this data into consideration under any future endangered 

species assessments. 

EPA statement

Reference (Page 45, 

Table 16)

Honeybee acute adult oral data is needed for risk assessment

Syngenta Comment: Syngenta notes that MRID 00162453 provided adult acute oral data. The

48-hr oral LD50 was > 200 μg fluazifop-P-butyl /bee. Syngenta respectfully proposes that 

MRID00162453 will satisfy the honey bee adult acute oral data requirement.

EPA Response: EFED agrees this data has been submitted. This study is adequate for a limit 

test and no new adult oral bee data are required.

EPA statement

Reference (page 46) Avian Reproduction (850.2300)

Estuarine/Marine Fish and Invertebrates (850.150. and 850.1400) 

Aquatic Plant Toxicity (850.4400, 850.4500 & 850.4550)

Syngenta Comment: The available data for fluazifop-P-butyl and other herbicides in the

same class demonstrate that the acid degradate for this class of compound is much less 

biologically active than the parent compound. Syngenta plans to submit (in a separate 

submission) additional toxicity data for parent and the acid degradate.

EPA Response: EFED will review these data upon submission.

Page 4 of 6
EPA statement

Reference (Appendix

B: Ecological

Toxicity Data, Page

65, Aquatic

Invertebrate Data)

(1) Water flea (Daphnia magna), MRID 00087490 (48 hr EC50=240.1 

ppm ae/281.2 ppm ai) and MRID 00162452 (48 hr LC50s=473.0 ppm

ae/553.9 ppm ai, 465.9 ppm ae/545.6 ppm ai, and 352.2 ppm 

ae/412.4 ppm ai for different R: S ratios.

(2) Mysid, 28 D LC50=66.35 ppb ae (77.7 ppb ai), MRID 00093805,

1981

Syngenta Comment: (1) Syngenta respectfully notes that MRID 00087490 and MRID

00162452 used the acid degradate rather than the parent compound. As both studies tested the 

toxicity of the acid degradate, a conversion to acid equivalent concentration is not needed and 

the endpoints should be 553.9 ppm, 545.6 ppm, and 412.4 ppm rather than 473.0 ppm ae,

465.9 ppm ae, and 352.2 ppm ae based on the acid concentration. Both MRID 00087490 and

MRID 00162452 demonstrate that the acid degradate has less biological activity to 

aquatic invertebrates than the parent.

(2) The mysid 28 d NOAEC of MRID 00093805 is 0.041 ppm ae (0.048 ppm ai).

EPA Response: 1. MRID 162451 used fluazifop-butyl as well as two EC formulations. This 

study was classified as unacceptable and can’t be used for risk assessment. MRID 162452 was 

deemed as supplemental with 48 hr EC50s of 553.9 mg/L for R:S 1:1, 467.1 mg/L for R:S 7:1 

and 412.4 mg/L for R:S 14:1 mixtures resulting in a classification of practically non-toxic. 2. 

This study was done using Fluazifop-butyl (122805). It was listed as supplemental and nonrepairable. The NOAEC for this study would be 15 ppb. This study needs to be repeated using 

Fluazifop-p-butyl (122809).

EPA statement

Reference (Page 66, 

Fish Data)

(1) Rainbow trout, 6.2 g, static, /Fluazifop-butyl, 98% ai, LC50 

99.909 ppm ae (117 ppm ai), MRID 00087483, 1981

(2) Fathead minnow, earlylife, flow-through, /Fluazifop-butyl, 90.2%,

30 D LOEC 0.203 ppm ae (0.238 ppm ai), MRID 00093808, 1981

Syngenta Comment: (1) The 96 hr LC50 for MRID 00087483 is 1.37 mg/L ai. The MRID for

this rainbow trout study is 00087487, 1981. As MRID 00087487 tested the toxicity of the acid 

degradate, a conversion to acid equivalent concentration is not needed and the endpoint should 

be 117 ppm rather than 99.9 ppm based on the acid concentration. Syngenta respectfully 

submits that this study confirms the low biological activity of the acid degradate to fish.

(2) This appears to be a typographic error. The fathead minnow 30-d NOEC is 0.203 ppm ae

(0.238 ppm ai), rather than the LOEC.

EPA Response: 1. EFED notes that the LC50 endpoint for the acid study is 117 ppm. This study 

was cited in the DER as Hill et al., 1981. 2. The acceptable 1981 study (MRID 93808) resulted 

in a 30 day NOAEL of 0.103 ppm, the highest test level with results visibly similar to the 

controls. This value was to be used until new data were submitted. The 1991 study (419006-02) 

was invalid because measured concentrations were inconsistent. 

EPA statement

Reference (page 67, 

Avian Data)

(1) All non-definitive endpoints are reported as less than values (“<”).

(2) Mallard duck, 9 D, dietary, /Fluazifop-P-butyl, 95% ai, MRID

00087481, 1987. 8 D LC50 4141.5 ppm ae (>4850 ppm ai)

Syngenta Comment: (1) Syngenta respectfully submits that all endpoints should be

Page 5 of 6
reported as greater than values (“>”). (2) The endpoint for MRID 00087481 is identified as a

LC50 value of > 21348 ppm ae (25000 ppm ai) rather than the cited 4141.5 ppm ae.

EPA Response: 1. EFED agrees, values should be > and not <. 2. This study (MRID 

00087481, 1980) is supplemental and did not meet guideline requirements. The ducks rejected 

food at all dose levels for the first 2 days of the study and at all doses but the lowest two 

treatment levels for the remainder of the test. The 25000 ppm ai endpoint was from the 1980 

supplemental study with Fluazifop butyl. The cited data were for Fluazifop-p-butyl (MRID 

41199201, 1987), although the endpoint should have been >4850 ppm ai). 

Page 6 of 6