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Table of Contents 

Contents

I. Introduction ............................................................................................................................. 3

II. Use and Usage/Background ...................................................................................................... 5

III. Scientific Assessments ......................................................................................................... 5

A. Human Health Assessment .................................................................................................... 5

Hazard Characterization and Risk .......................................................................................... 5

Food Tolerances ...................................................................................................................... 6

Human Incidents ..................................................................................................................... 6

B. Environmental Assessment ................................................................................................... 7

Ecological Risk Characterization ............................................................................................ 7

Ecological Risk Assessment Uncertainties ............................................................................. 9

Ecological Incidents .............................................................................................................. 10

Endangered Species Assessment .......................................................................................... 10

C. Endocrine Disruptor Screening Program ............................................................................. 11

IV. Proposed Interim Registration Review Decision ............................................................... 12

IV. Next Steps and Timeline .................................................................................................... 16

Appendix A: Summary of Proposed Actions Taken for Flutolanil ............................................. 17

Appendix B: Flutolanil Label Table ............................................................................................ 18

Appendix C: Risk Quotient Ranges ............................................................................................. 19
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I. Introduction 

This document is the Environmental Protection Agency’s (EPA or the Agency) Proposed 

Interim Registration Review Decision for flutolanil and is being issued pursuant to 40 CFR 

sections 155.56 and 155.58. A registration review decision is the Agency's determination 

whether a pesticide meets, or does not meet, the standard for registration in the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it 

determines it to be appropriate, a proposed interim registration review decision before 

completing a registration review. Among other things, the proposed interim registration review 

decision may require new risk mitigation measures, impose interim risk mitigation measures, 

identify data or information required to complete the review, and include schedules for 

submitting the required data, conducting the new risk assessment and completing the registration 

review. For further information on flutolanil, additional documents can be found in EPA’s public 

docket (EPA-HQ-OPP-2008-0148) at www.regulations.gov. 

 FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific data showing that they will not cause 

unreasonable risks to human health or to the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

and reduce risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the Agency periodically reevaluates pesticides to make sure that as these changes 

occur, products in the marketplace can continue to be used safely. Information on this program is 

provided as www.epa.gov/oppsrrd1/registration_review/. 

In 2006, the Agency implemented the registration review program pursuant to FIFRA 

section 3(g) and will review each registered pesticide every 15 years to determine whether it 

continues to meet the FIFRA standard for registration. 

Flutolanil is a systemic fungicide first registered by EPA in 1993. Because it was 

registered after November 1984, flutolanil was not subject to reregistration. It is registered for 

use to control fungal diseases in both food crops (peanuts, potatoes, rice, Cole crops, turnip 

greens, and seed piece treatments on potato, cotton, sugar beet and soybean) and non-food sites 

(turf, greenhouse, field-grown and potted ornamentals). Flutolanil forms a protective barrier 

on the plant, enters the plant, and moves upward in the xylem. Flutolanil has both protective 

and curative activity. 

Pursuant to 40 CFR section 155.50, EPA formally initiated registration review for 

flutolanil (case # 7010). The following highlights significant events that have occurred during the 

registration review of flutolanil: 

 September 15, 2008– Publication of Flutolanil Summary Document for a 60-day public 

comment period. The Summary Document included the Preliminary Work Plan (PWP) 

and was accompanied by the scoping document and problem formulation. 
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 February 5, 2009- Final Work Plan (FWP) for flutolanil was issued. One public comment 

was received during the 60-day comment period for the flutolanil PWP but it did not 

change the risk assessments needed, data needs or the timeline in the PWP. The FWP did 

modify the PWP to remove the analytical standards data requirement for metabolites and 

to add the UV/Visible light absorption data requirement. 

 April 7, 2010 – Generic Data Call-In Notice (GDCI) for flutolanil issued. 

 March 28, 2014 – The Agency published the Draft Preliminary Environmental Fate and 

Ecological Risk Assessment for the Registration Review Combined with the 

Environmental Fate and Ecological Risk Assessment for Proposed Amendments to 

Certain Labels for Flutolanil and the Flutolanil – Preliminary Human Health Risk 

Assessment for Registration Review and Human Health Risk Assessment for Label 

Amendments for Brassica (Cole) Leafy Vegetables (Crop Group 5), Turnip Greens, Rice, 

and Turf in Addition to Banded Applications on Peanuts for a 60-day public comment 

period. No comments were received during the comment period. 

 September 2014 – The Agency is now publishing the Flutolanil Proposed Interim 

Registration Review Decision in docket number EPA-HQ-OPP-2008-0148 for a 60-day 

public comment period.

Additional information on flutolanil can be found in EPA’s public docket, EPA-HQ-OPP2008-0148, accessed at www.regulations.gov. 
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II. Use and Usage/Background 

Flutolanil is a fungicide registered for the control of fungal diseases on peanuts, potatoes, 

rice and other crops (such as leafy vegetables, cole crops, and seed treatment for cotton, sugar 

beets, and soybean), turf, greenhouses, and ornamentals. Peanuts and potatoes are the prominent 

use sites for flutolanil, accounting for more than 99% of flutolanil usage in the U.S. between 

2008-2012. The rice use is the least, with percent crop treated (PCT) with flutolanil less than 1%. 

For the period 2008-2012, the average PCT with flutolanil for peanuts and potatoes (foliar) was 

15% and 10%, respectively, while for potato seed treatment PCT was 5% percent. 

When compared with other registered fungicides, flutolanil is a viable alternative for 

control of white mold, (caused by Sclerotium sp.) & limb/pod rot (caused by Rhizoctonia sp.) on 

peanuts, Rhizoctonia diseases (scurf and blight) on potatoes (seed and foliar treatment), and 

Rhizoctonia diseases on turf and ornamentals. For turf and ornamental uses of flutolanil as an 

succinate dehydrogenase inhibitor (SDHI) fungicide is considered a useful partner that may be 

alternated with other fungicide chemistries (such as demethylation inhibitors (DMI) and quinone 

outside inhibitor (QoI) fungicides) to provide effective resistance management as well as

effective disease control. Flutolanil use on turf and ornamentals is typically limited to treatment 

for Rhizoctonia diseases and as such is highly dependent on disease pressure in a given season as 

well as typical use patterns that involve spot treatments where pockets of disease may be 

observed or anticipated.

III. Scientific Assessments 

 A. Human Health Assessment 

A summary of the Agency’s human health risk assessment is presented below. The 

Agency used the HED scoping document, its supporting documents, and the most updated 

Agency science policies and risk assessment methodologies to prepare a qualitative risk 

assessment, including a quantitative chronic dietary assessment, in support of the registration 

review of flutolanil. The most recent human health risk assessment was conducted in February 

2014. For a detailed discussion, see the Flutolanil – Preliminary Human Health Risk Assessment 

for Registration Review and Human Health Risk Assessment for Label Amendments for Brassica 

(Cole) Leafy Vegetables (Crop Group 5), Turnip Greens, Rice, and Turf in Addition to Banded 

Applications on Peanuts, published on March 28, 2014 in the public docket EPA-HQ-OPP-2008-

0148, which can be accessed on http://www.regulations.gov/. The Agency did not receive any 

comments on the risk assessment. 

Hazard Characterization and Risk 

There are no dietary, residential, occupational, or aggregate risks of concern for 

flutolanil. Flutolanil has few biologically significant toxicological effects, which are mainly in 

the liver and gastrointestinal (GI) system. The flutolanil data do not indicate that it is neurotoxic, 

or that it targets the immune system, fetal development, or reproduction. No dermal effects were 

observed, and the subchronic inhalation study was waived based on a weight-of-evidence 

approach; therefore no toxicological endpoints were established for any dermal or inhalation 
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exposure duration. No hazard was identified for incidental oral exposure. The only endpoint that 

could be identified was for chronic dietary exposure. The chronic dietary exposure estimates for 

food and drinking water are below the level of concern for the general U.S. population and for 

infants (<1 year), the most exposed subgroup. 

No dermal, incidental oral, or inhalation toxicological endpoints attributable to short- or 

intermediate-term exposures have been identified, and long term residential exposure and 

chronic occupational exposure are not expected. Therefore, quantitative residential handler, postapplication, occupational, and short- and intermediate term aggregate assessments were not 

required. Chronic aggregate exposure (food and drinking water) was assessed but the resultant 

risk estimates were not of concern, as stated above. 

 It has not been determined that flutolanil shares a common mechanism of toxicity with 

other chemicals; therefore a cumulative risk assessment was also not required. Flutolanil is 

further characterized as “not likely to be carcinogenic to humans.” 

Food Tolerances 

Tolerances for flutolanil are established in 40 CFR §180.484 for residues of flutolanil, N-

(3-(1-methylethoxy) phenyl)-2-(trifluoromethyl) benzamide, including its metabolites and 

degradates, in or on commodities. Tolerances are established [40 CFR §180. 484(a)] on rice 

straw and hulls but are no longer required because they are no longer considered significant 

feedstuffs for any livestock (Table 1 Feedstuffs, June 2008) and should be removed. Based on 

the OECD tolerance calculation procedures on peanut hay, including residues from both band 

and broadcast applications, the established tolerance of 15.0 ppm for peanut hay should be 

increased to 20.0 ppm. The tolerance of 0.1 ppm on turnip greens and the Brassica (cole) leafy 

vegetable group 5 should be increased to 0.20 ppm; this is a reconsideration of previous 

recommendations, because detectable residues of parent were found in one field trial on mustard 

greens. 

The US tolerance expression harmonizes with the Codex tolerance expression for 

livestock commodities but not for plants. The US tolerance expression for plant and livestock 

commodities is flutolanil and its metabolites converted to 2-(trifluoromethyl) benzoic acid and 

calculated as flutolanil, whereas the Codex tolerance expression for plants is flutolanil. For 

animal commodities, the Codex tolerance expression is flutolanil and its transformation products 

containing the 2-(trifluoromethyl) benzoic acid moiety. 

There are no Codex, Canadian, or Mexican MRLs for peanuts, turnip greens, or the 

Brassica (cole) leafy vegetables. Codex MRLs are established on rice grain, bran, and straw. 

Codex and US tolerance levels are the same for rice bran and rice straw, but are different for rice 

grain, i.e., 7.0 ppm in the US compared to 2.0 for husked rice grain and 1.0 for polished rice 

grain for Codex. For livestock commodities, most Codex tolerance levels are the same as the US 

tolerance levels. However, the US tolerances for the livestock liver and kidney are higher than 

the Codex MRLs and cannot be harmonized.

Human Incidents 
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The incident analyses of the Main and Aggregate Incident Data System (IDS) was 

updated in July 2013 to include the time period January 1, 2008 to May 8, 2013, where there was 

one incident reported that involved flutolanil that was part of a lawsuit and was not considered in 

this update. There were three incidents identified in Aggregate IDS that involve flutolanil, which 

were classified as minor severity. The incident analysis of the National Institute of Occupational 

Safety and Health Sentinel Event Notification System for Occupational Risks (NIOSH 

SENSOR) was updated in July 2013 to include the time period from 1998 to 2009. One incident 

was identified in SENSOR involving flutolanil. This case occurred in New York in 2006, 

involved multiple active ingredients, and was moderate in severity. 

The current incident analysis is consistent with the previous analysis. Based on the 

continued low frequency and severity of incident cases reported for flutolanil, there does not 

appear to be a concern at this time that would warrant further investigation. The Agency will 

continue to monitor the incident information and if a concern is triggered, additional analysis 

will be conducted. 

B. Environmental Assessment 

 The risk assessment evaluates risks to species that are not subject to the Endangered 

Species Act (ESA) and provides a screening level assessment for potential risks to listed species 

under the ESA. A summary of the Agency’s environmental risk assessment for flutolanil is 

presented below. For detailed discussions of all aspects of the environmental risk assessment, 

see the Draft Preliminary Environmental Fate and Ecological Risk Assessment for the 

Registration Review Combined with the Environmental Fate and Ecological Risk Assessment for 

Proposed Amendments to Certain Labels for Flutolanil published on March 28, 2014 in the 

public docket EPA-HQ-OPP-2008-0148, which can be accessed on http://www.regulations.gov/. 

The Agency did not receive any comments on the risk assessment. 

Ecological Risk Characterization 

Acute and chronic risk quotients exceeded levels of concern (LOC) for several taxa from 

the use of flutolanil on a number of different use sites in accordance with current labels. In 

particular, acute and chronic LOCs were exceeded for freshwater fish and estuarine/marine 

pelagic (in the water column) and benthic invertebrates, as well as for aquatic non-vascular 

plants and terrestrial dicot plants. 

Acute risk is below the level of concern (LOC) for estuarine/marine fish. However, there 

is uncertainty as to whether exposure could exceed the chronic LOC for estuarine/marine fish, 

the acute and chronic LOCs for freshwater pelagic and benthic invertebrates, and the acute and 

chronic LOCs for birds and mammals. These uncertainties arise because definitive endpoints 

were not reached in the relevant toxicity studies due to lack of effects, and the true No Observed 

Adverse Effect Concentrations (NOAEC) fall somewhere above the highest treatment 

concentration. Estimated Environmental Concentrations (EEC’s) may be above the nondefinitive endpoint and so there is the potential to exceed the LOC. These risks are explained in 

more detail below. The range of risk quotients (RQ’s) for different scenarios are provided for 

each taxon in Appendix C. 
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Risk to Aquatic Organisms

Acute LOCs were exceeded for listed and non-listed freshwater fish and aquatic phase 

amphibians for nursery uses and on ornamentals. The acute LOC was exceeded for only listed 

freshwater fish and aquatic phase amphibians for the turf use, and for aerial application to 

peanuts and rice. Chronic risk LOCs were exceeded for freshwater fish and aquatic phase 

amphibians for rice and nursery and ornamentals uses, based on the chronic toxicity study which 

showed reductions in length, but no significant physical/behavioral abnormalities. 

Acute and chronic risk LOCs were exceeded for listed and non-listed estuarine/marine 

pelagic and benthic invertebrates for most uses, including peanuts, rice, turf, and nurseries and 

ornamentals. Flutolanil was shown to be at least one order of magnitude more toxic to 

estuarine/marine invertebrates than to freshwater invertebrates on an acute and chronic basis. It is 

highly acutely toxic to mysid shrimp, with 90% and 100% mortality seen at the two highest test 

concentrations. In the chronic shrimp study, a reduction in survival, weight, and the number of 

young was seen. Acute LOCs were also exceeded for listed estuarine/marine pelagic and benthic 

invertebrates for potatoes and soybean; the listed and non-listed chronic LOC was also exceeded 

for potatoes and soybean. 

The LOC for acute listed and non-listed freshwater invertebrates is potentially exceeded 

for nursery and ornamentals uses, and potentially exceeded for listed freshwater invertebrates for 

rice. In the acute pelagic test an EC50 was not reached at the limit of solubility for flutolanil, 

resulting in non-definitive endpoints. However, mortality did reach 45% at that concentration. In 

the chronic pelagic toxicity study, length, time to first brood, and number young were all 

significantly reduced; the LOC for listed and non-listed chronic freshwater invertebrates was 

exceeded for rice and nurseries and ornamentals. No effects were seen in benthic freshwater 

invertebrate acute studies and endpoints were non-definitive; however, the magnitude the EECs 

for nursery and ornamental uses is such that a potential LOC exceedance could be possible. The 

LOCs for risks to chronic benthic invertebrates is also exceeded when using pore water EECs for 

nursery and ornamental uses. 

No mortality was observed in the acute study for estuarine and marine fish, but sublethal 

effects were seen at the two highest test concentrations. A chronic study is not available; 

however, a potential for chronic risk exists for estuarine/marine fish based on behavioral effects 

in the acute study and the establishment of a chronic NOAEC in the freshwater chronic study. 

Risk to Terrestrial Organisms 

Flutolanil is practically non-toxic to birds on acute oral and subacute dietary basis. The 

oral toxicity and dietary studies in bobwhite and mallard showed no mortality, no other effects, 

and had non-definitive endpoints. However, the magnitude of the screening-level EECs for turf 

and nursery uses is great enough that these exposures have the potential to exceed listed and nonlisted LOCs if there would be mortality to birds at exposures greater than the highest tested in the 

acute toxicity studies. There are chronic RQ exceedances of the listed and non-listed LOC for 

turf and nursery uses. There is a definitive NOAEC from the bobwhite reproduction study 
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showing no effects other than a slight reduction in number of eggs laid, which is biologically 

meaningful. The mallard reproduction study showed a statistically significant reduction in 

eggshell thickness at the highest concentration tested. Birds also serve as a surrogate for reptiles 

and terrestrial phase amphibians, to which these results also apply. 

Flutolanil is practically non-toxic to mammals on an oral acute basis, and there were no 

reproductive effects. Endpoints were non-definitive, but as with birds, the screening-level EECs 

for turf and nursery and ornamentals were great enough that there is a potential that acute and 

chronic LOCs could be exceeded. 

Flutolanil is practically non-toxic to insects, based on an acute contact toxicity study with 

adult honeybees. 

Risk to Plants 

For terrestrial plants, the seedling emergence study showed significant effects on 

emergence, survival, and height, with dicots being slightly more sensitive than monocots. 

However some species tested showed promotion of emergence. The vegetative vigor study also 

generally showed promotion of survival and height, and weight in some species or no reduction 

in survival for dicots, and therefore no definitive endpoint could be determined based on lack of 

toxicity. For monocots there were effects at the lowest and highest treatment concentrations and 

so a definitive endpoint could not be determined, and risk could not be estimated. EPA’s LOC is 

exceeded for listed and nonlisted terrestrial plants from the use on turf and nursery stock. 

For aquatic vascular and non-vascular plants, the endpoints were non-definitive for all 

species tested. There were significant reductions in frond/cell counts at a single concentration 

exposure that was greater than the solubility limit for flutolanil, used in all studies except the 

freshwater diatom. However, the EECs for listed aquatic nonvascular plants exceed the acute 

LOC for at least rice and nursery uses, and potentially for other uses as well. There were no LOC 

exceedances for listed aquatic vascular plants, but some uncertainty due to screening-level EECs 

greater than the non-definitive endpoints. There are no LOC exceedances for nonlisted aquatic 

vascular plants. 

Ecological Risk Assessment Uncertainties 

Exposure 

Exposure to aquatic animals and plants in aquatic environments were modeled with the 

Pesticide Root Zone Model and Exposure Analysis Modeling System (PRZM/EXAMS) to 

provide estimated environmental concentrations (EECs) which were compared to toxicity values 

to calculate risk. A number of conservative assumptions were included in this Tier 1 risk 

assessment. EECs are based on maximum labeled single use rates, which are likely lower based 

on typical use information (BEAD, 8/8/2014). For example, the average application rate for 

peanuts is 0.4 pounds of active ingredient (lbs a.i.) per acre, 0.5 lbs. a.i. for potatoes (foliar and 

seed) and 0.3 lbs. a.i. for rice (2008-2012, EPA Proprietary Data). For aquatic modeling, the risk 

assessment assumed between 0.742-2.00 lbs a.i/acre for peanuts, 0.36 (seed)-0.77 lbs a.i./acre for 

potatoes, and 0.490-0.980 lbs a.i./acre for rice. Also, since the chemical shows medium to high 
10

pest resistance (as indicated by Fungicide Resistance Action Committee for chemicals in Group 

7), it may not be applied as often to rice as modeled in PRZM/EXAMS. 

Also, field dissipation studies with flutolanil point towards lower persistence than noted 

from the results of PRZM/EXAMS. Since there is only one, instead of two, sediments in the 

aquatic metabolism study, and the study only examines short time durations, the results were 

extrapolated, introducing a 3X uncertainty factor into the aquatic modeling results. Finally, the 

standard pond used in PRZM/EXAMS does not include flow or turnover, among other things, 

which may remove part of the flutolanil received in the pond. 

The bioavailability of flutolanil in aquatic media is uncertain due to low to moderate 

recoveries of the test material and precipitate observed in some studies; this could underestimate 

risk to aquatic organisms. 

Nursery Use 

The risks calculated from use of flutolanil on nursery stock are likely overestimated. It is 

likely that for the nursery scenario, there is lower persistence than what was modeled using the 

standard input parameters. Considering lower persistence, the FL nursery (soil drench) scenarios 

yield acute and chronic RQs that are approximately 2.3 fold less than those derived from 

standard input parameters. Acute and chronic risk to estuarine/marine invertebrates remains 

above the listed and nonlisted LOC for both uses including these modified parameters, but acute 

and chronic risk to all other assessed taxa falls below the nonlisted level of concern. 

Turf Use 

As a refinement for the turf use for risk to estuarine/marine invertebrates, the spray drift 

value was decreased considering the buffer zone of 100 feet towards freshwater bodies of water 

for ground applications currently on most labels, decreasing EECs. The buffer may also decrease 

EEC’s further due to reductions in runoff, which cannot be quantified. However when compared 

to the available acute and chronic toxicity data for estuarine/marine pelagic and benthic 

invertebrates, the refined scenarios of exposure resulted in RQs that were very similar to those 

that were estimated without the use of a buffer zone. 

Ecological Incidents 

An October 2013 search of OPP’s Ecological Incident Information System of all years of 

available data up until October 2013 resulted in one incident of yellowing and stunting of oats, 

which was classified as “unlikely” to be due to flutolanil exposure. No incidents were found in 

the Incident Database System, of all years of available data up until October 2013. There were no 

bird incidents in the American Bird Conservancy and Avian Incident Monitoring System 

databases, of all years of available data up until October 2013. 

Endangered Species Assessment 

In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the 

National Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department 
11

of Agriculture (USDA) released a summary of their joint Interim Approaches for assessing risks 

to listed species from pesticides. The Interim Approaches were developed jointly by the 

agencies in response to the National Academy of Sciences’ (NAS) recommendations and reflect 

a common approach to risk assessment shared by the agencies as a way of addressing scientific 

differences between the EPA and the Services. The NAS report outlines recommendations on 

specific scientific and technical issues related to the development of pesticide risk assessments 

that EPA and the Services must conduct in connection with their obligations under the 

Endangered Species Act (ESA) and FIFRA. 

The joint Interim Approaches were released prior to a stakeholder workshop held on 

November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the 

December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues 

Research and Evaluation Group (SFIREG) meetings, and held a stakeholder workshop in April 

2014, allowing additional opportunities for stakeholders to comment on the Interim Approaches. 

As part of a phased, iterative process for developing the Interim Approaches, the agencies will 

also consider public comments on the Interim Approaches in connection with the development of 

upcoming Registration Review decisions. The details of the joint Interim Approaches are 

contained in the white paper “Interim Approaches for National-Level Pesticide Endangered 

Species Act Assessments Based on the Recommendations of the National Academy of Sciences 

April 2013 Report,” dated November 1, 2013. 

Given that the agencies are continuing to develop and work toward implementation of the 

Interim Approaches to assess the potential risks of pesticides to listed species and their 

designated critical habitat, the ecological risk assessment supporting this Proposed Interim 

Registration Review Decision for flutolanil does not contain a complete ESA analysis that 

includes effects determinations for specific listed species or designated critical habitat. Although 

EPA has not yet completed effects determinations for specific species or habitats, for this 

preliminary assessment EPA conducted a screening-level assessment for all taxa of non-target 

wildlife and plants that assumes for the sake of the assessment that listed species and designated 

critical habitats may be present in the vicinity of the application of flutolanil. This screening 

level assessment will allow EPA to focus its future evaluations on the types of species where the 

potential for effects exists once the scientific methods being developed by the agencies have 

been fully vetted. While the agencies continue to develop a common method for ESA analysis, 

the regulatory section of the Proposed Interim Registration Review Decision document will 

describe the level of ESA analysis completed for this particular registration review case. Once 

the agencies have fully developed and implemented the scientific methods necessary to complete 

risk assessments for endangered and threatened (listed) species and their designated critical 

habitats, these methods will be applied to subsequent analyses for flutolanil as part of completing 

this registration review. 

C. Endocrine Disruptor Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 
12

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision for flutolanil, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

flutolanil is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to an 

effect produced by a “naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.” The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify 

the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or 

T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the 

potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP 

where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available 

data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the 

substance, and establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131

 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.2

 

Flutolanil is on List 1 for which EPA has received all the required Tier 1 assay data. The 

Agency is currently reviewing all of the assay data received for the appropriate List 1 chemicals 

and planning to make the conclusions of those reviews available in early 2015. 

 

In this proposed interim decision, EPA is making no human health or environmental 

safety findings associated with the EDSP screening of flutolanil. Before completing this 

Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination. 

IV. Proposed Interim Registration Review Decision 

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this 

proposed interim registration review decision document for flutolanil. Except for the EDSP and 

ESA components of the flutolanil registration review case, the Agency has made the following 

 

1

 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals. 

2 http://www.epa.gov/endo/
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proposed interim decision: (1) no additional data are required at this time; and (2) changes are 

required to flutolanil product labels. 

Pending consideration under the Endocrine Disruptor Screening Program, the Agency has 

identified no human dietary, residential, occupational, or aggregate risks of concern for 

flutolanil. The qualitative risk assessment performed in support of the registration review of 

flutolanil supports this conclusion in compliance with the most updated Agency science policies 

and human health risk assessment methodologies. As a result, no revision of flutolanil labels is 

currently necessary to address any human health risk concerns. 

The proposed mitigation focuses on ecological risk to estuarine and marine invertebrates, 

the taxon for which there were the most acute and chronic risk exceedances, and also on risk to 

freshwater fish. Peanuts and potatoes are the prominent use sites for flutolanil, accounting for 

more than 99% of flutolanil usage in the U.S. between 2008-2012. These uses also had the 

lowest RQ’s and LOC exceedances. The rice use is the least prominent, with PCT with flutolanil 

less than 1%. One registrant, Gowan, has indicated that they intend to voluntarily cancel their 

registrations of flutolanil. 

For the peanut use, the predominant use of flutolanil, RQs are at the acute LOC from drift 

and runoff for listed freshwater fish (acute), and above the LOCs for listed and non-listed 

estuarine/marine invertebrates (acute and chronic) in the water column and the benthos. The 

highest RQs correspond to aerial applications, and the exceedance for listed freshwater fish is 

only for aerial application. However, 95% of the applied flutolanil to peanuts was via ground 

application, with only 5% applied aerially (BEAD, 8/8/2014). According to the registrant, the 

aerial application is used when the fields are too wet to apply flutolanil via ground application. 

Acute and chronic RQ’s also exceed LOCs for estuarine/marine invertebrates in the water 

column and the benthos for potato and soybean uses, although these exceedances are marginal. 

The acute LOC exceedances are for listed estuarine/marine invertebrates only, while the chronic 

LOC exceedances are for both listed and non-listed estuarine/marine invertebrates. Acute and 

chronic RQs for listed and non-listed freshwater fish, and for listed and nonlisted estuarine 

marine invertebrates in the water column and benthos, were also exceeded for turf, rice, and 

nursery uses. 

In order to reduce offsite exposure from spray drift, the registrant with all of the flutolanil 

turf and nursery use registrations, Bayer Environmental Science, has agreed to change their 

labels to require applicators to use a Medium droplet size spectrum or coarser for all uses of 

flutolanil, as defined by the American Society of Agricultural and Biological Engineers 

(ASABE) standard 572. Nichino, the registrant with all of the peanut use registrations, has 

agreed to this droplet size restriction for the aerial application to peanuts. The highest RQs are 

for aerial applications, which accounts for 5% of flutolanil application to peanuts, with 95% of 

the applied flutolanil to peanuts was via ground application. The proposed label changes 

requiring at least a Medium droplet size spectrum should reduce the mass of flutolanil that might 

drift from applications to all use sites and should reduce the potential for risk to all non-target 

organisms off of treated fields. 
14

In addition to the spray drift restrictions described above, Bayer Environmental Science 

has agreed that all turf labels for flutolanil will include a 100-foot buffer from turf applications to 

estuarine or marine habitat, and to ditches, drainage tiles, or other waterways that drain directly 

into (within 1⁄2 mile of) estuaries and marine habitats. Such language is currently on some of the 

flutolanil turf use labels, but some are currently missing this language. The ecological risk 

assessment considered the effect a 100-foot buffer would have on spray-drift exposure to 

estuarine and marine invertebrates, but was not able to quantify the resulting reduction of 

flutolanil transport in runoff. It is clear, however, that extending this mitigation to all turf labels 

should reduce to some extent the overall mass of flutolanil reaching estuaries from use on turf. 

Similarly, the rice use had some of the highest predicted exposure for aquatic organisms 

of all registered uses of flutolanil. However, current label language prohibits the use of flutolanil 

application within 3 miles of any estuarine/marine waterway or watershed, which was not 

accounted for quantitatively in calculating RQs. EECs are likely overestimated and so all RQs 

that exceeded the LOCs for the use on rice are also likely to be overestimated. Although 

flutolanil does not degrade readily under most testing conditions, field studies did not show very 

high persistence overall. Aquatic metabolism, dilution, and binding to sediments and particulate 

in the course of a 3-mile travel to encounter an estuarine/marine body of water will contribute to 

the dissipation of flutolanil. In addition, based on usage information over the years 2008-2012, 

the use on rice has decreased significantly, to only <1% of PCT with flutolanil. Therefore, EPA 

is not proposing any further mitigation for the use of flutolanil on rice. 

Finally, Bayer Environmental Science has agreed that all of their flutolanil labels with 

uses on ornamental nursery stock will only allow four applications per year. This language is 

currently missing from one of their ornamental nursery-use labels. The nursery uses had the 

largest LOC exceedances for most taxa in the risk assessment, but EECs can be refined when 

considering nursery practice. For example, if the maximum rate were used for foliar application 

then a maximum annual application would be 2.1 lb; for container nurseries, there could be 2.93 

lb ai per acre if all pots were treated (BEAD 8/8/2014). This is compared to use rates of 9.78 lbs 

(ground application) to 21.5 lbs (soil drench) used in the risk assessment. In addition, as 

described above, the calculated exposure from the nursery use may have been overestimated due 

to the persistence of flutolanil simulated in exposure modeling. As a result, the Agency is not 

pursuing additional mitigation for use of flutolanil in nurseries beyond those described above. 

The Agency does not propose additional changes to flutolanil labels at this time to 

address potential risk to birds and mammals. The ecological risk assessment indicated that a 

potential for LOC exceedances remained due to high screening-level EECs for turf and nursery 

stock. However, the RQs that suggest this possibility for acute and chronic risk to mammals and 

acute risk to birds are derived from studies in which no toxic effects were observed, which 

makes the potential for risk highly uncertain. 

Screening-level chronic RQs for birds exceeded the LOC for several turf uses and for use 

in nurseries, but the potential for and extent of possible risk is uncertain. The magnitude of the 

RQs is less than 2 for most of these uses, which suggests that exposures of concern would not 

extend beyond the treated field, and that RQs calculated with typical instead of maximum 

screening EECs would be below the level of concern for most uses. In addition, the highest of 

the RQs which exceed the chronic LOC are for small birds consuming only short grass, which 
15

would represent a very small portion of potentially exposed birds. Finally, birds would not likely 

derive all of their food from some of the use sites modeled, such as golf tees, greens and aprons, 

and nurseries. Nonetheless, the spray droplet-size restrictions that are proposed to be 

incorporated on flutolanil product labels should reduce off-site transport of flutolanil, and should 

reduce the potential for chronic risk to birds. 

The Agency does not propose additional changes to flutolanil labels at this time to 

address potential risk to terrestrial plants. The screening level risk assessment resulted in risk 

quotients for non-listed, semi-aquatic plants at the LOC of 1.0 for golf-course fairways and the 

highest calculated application rate for nurseries. As indicated above, this maximum rate used in 

the risk assessment may not reflect actual nursery practices, suggesting that the risk quotient at 

the LOC may well be an overestimate. In addition, the model used to estimate potential exposure 

to semi-aquatic plants only considers areas directly adjacent to the treated area, assuming a set 

amount of runoff that does not take local soil and weather conditions into account. Finally, the 

RQ at the non-listed plant LOC was based on the most sensitive plant tested, and may not 

represent all plants well; flutolanil actually enhanced seedling emergence and vegetative vigor in 

a number of plant species tested. Nonetheless, the spray droplet-size restrictions and buffer from 

aquatic features for turf applications that are proposed to be incorporated on flutolanil product 

labels should reduce off-site transport of flutolanil, which will further reduce the potential for 

risk to semi-aquatic plants. These measures could also reduce the potential for exposure to listed 

plants, for which the risk assessment indicated some LOC exceedances. The extent to which any 

listed plants might be exposed will be determined in future consultation on flutolanil with the 

Fish and Wildlife Service. 

The Agency also does not propose additional changes to flutolanil labels at this time to 

address potential risk to aquatic plants. Most vascular and non-vascular plants tested had no 

toxicity endpoint established at concentrations that indicate no risk at the screening level. There 

is uncertainty associated with RQs for the most sensitive aquatic plant tested, a freshwater 

diatom. However, while these RQs were based on a study in which some effects to the diatoms 

were observed, the effects were not sufficient to establish a toxicity endpoint for the risk 

assessment. Nonetheless, as with other aquatic taxa, the spray droplet-size restrictions and buffer 

from aquatic features for turf applications that are proposed to be incorporated on flutolanil 

product labels should reduce off-site transport of flutolanil, which should further reduce the 

potential for risk to aquatic plants. 

In the interim, EPA is making no human health or environmental safety findings 

associated with the EDSP screening of flutolanil. While the risk assessment supporting this 

Proposed Interim Registration Review Decision evaluates risks to species that are not subject to 

the ESA, it is premature to make effects determinations for listed species until the interim 

approaches developed in response to the National Academy of Science (NAS) April 2013 report 

are vetted; therefore, EPA has not completed effects determinations for listed species associated 

with the registered uses of flutolanil. Therefore, consultation with the Fish and Wildlife Service 

and National Marine Fisheries Service (the Services) on the potential risk of flutolanil to listed 

species will be necessary. The Agency is issuing a proposed interim registration review decision 

pending the evaluation of potential endocrine disruptor risk and consultation with the Services. 

Before completing this Registration Review, the Agency will make an EDSP FFDCA section 

408(p) determination and an endangered species effects determination under the ESA. The 
16

Agency is issuing a Proposed Interim Registration Review Decision pending completion of the 

ESA and EDSP assessments. 

IV. Next Steps and Timeline 

A. Interim Registration Review Decision

A Federal Register Notice will announce the availability of this Proposed Interim 

Registration Review Decision for flutolanil and allow a 60-day comment period. If there are no 

significant comments or additional information submitted to the docket during the comment 

period that leads the Agency to change its decision, EPA may issue an interim registration 

review decision for flutolanil (case 7010). However, a final decision for flutolanil may be issued 

without having previously issued an interim decision. A final decision on the flutolanil 

registration review case will occur after an EDSP FFDCA section 408(p) and ESA 

determinations have been made. 

B. Implementation of Mitigation Measures 

Once the Interim Registration Review Decision is issued in final form, registrants will 

need to submit proposed amended labels that include the agreed-upon end risk mitigation and 

submit them to the Agency for approval within 60 days of issuance of the Interim Registration 

Review Decision. The mitigation measures and label amendments are described in Appendix A 

and B. 
Appendix A: Summary of Proposed Actions Taken for Flutolanil Registration Review Case#: 7010PC Code: 128975Chemical Type: FungicideChemical Family: phenyl‐benzamide (benzanilide)Mode of Action: succinate‐dehydrogenase respiration inhibitor (SDHI)

Affected Population(s) Source of Exposure Route of Exposure Duration of

Exposure

Risk(s) of Concern Action

Freshwater fish Water (direct contact, non‐dietary) Ingestion

Dermal absorption

AcuteChronic

Acute Toxicity

Chronic toxicity ‐ growth Bu

Specify 

larger d

Restrict 

appl

Aquatic Invertebratesestuarine/marine

Water (direct contact, non‐dietary) Ingestion

Dermal absorption

AcuteChronic

Acute Toxicity

Chronic toxicity ‐ 

reproduction
Appendix B: Flutolanil Label Table 

Summary of Proposed Labeling Changes for Flutolanil Uses 

Description Amended Labeling Language for Flutolanil Use Products 

End Use Products

Use Precautions – Products labeled for turf and ornamentals 

“For use rates over x oz. per 1000 sq ft, do not apply within 100 feet of any estuary or marine habitat or within of any ditches, drainage tiles, or other waterways that drain directly into (within 1⁄2 mile) estuaries and marine ha

Apply no more than a combined total of x oz. per 1000 square feet as a broadcast application during a single groseason.” 

General Information - Products labeled for turf and ornamentals 

“Make no more than 4 applications of (product) per year to ornamental plantings.” 

Spray Drift Management “Spray equipment and weather affect spray drift. Consider all factors when making application decisions. Wher

have more stringent regulations, they must be observed. Avoiding spray drift is the responsibility of the applicatgrower. To reduce the potential for drift, the application equipment must be set to apply Medium or larger dropl

ASABE Standard 572) with corresponding spray pressure. Use high flow rate nozzles to apply the highest practspray volume, using the appropriate droplet size to ensure adequate canopy distribution, coverage, and penetratiWith most nozzle types, narrow spray angles produce larger droplets. Follow the nozzle manufacturer’s directiopressure, orientation, spray volume, etc., in order to minimize drift and optimize coverage and control.” 
Appendix C: Risk Quotient Ranges Bolded values represent an LOC exceedance. Italicized values represent a “potential” LOC exceedance. 3 Acute and chronic risk to estuarine/marine fish was not estimated as there were no mortalities in the acute study up to solubility limit and no ch

is available. An acute-to-chronic ratio (ACR) was not utilized to estimate chronic toxicity as there is a high level of uncertainty in using an ACR 

acute toxicity endpoint. 

FW fish FW 

invertebrates 

E/M Fish3 E/M 

invertebrates 

FW benthic invertebrates 

E/M benthic invertebrates 

Birds Mamm

Use 

(inclusive of 

all 

scenarios)

Acute RQ 

Chronic RQ 

Acute RQ 

Chronic RQ 

Acute RQ 

Chronic 

Acute RQ 

Chronic RQ 

Acute RQ 

Chronic RQ 

Acute RQ 

Chronic RQ 

Acute RQ 

Chronic RQ 

Acute RQ 

Peanuts 0.05 0.23-

0.99 

2.64-11.2 

0.22-0.94 

2.55-10.8 

<0.12-0.38 

Potato 0.06-

0.23 

1.10-2.65 

0.06-0.23 

1.09-2.60 

Cotton Soybean 0.15 1.74 0.14 1.65 Sugar beet Rice 0.33- 

0.46 

1.59-1.96 

<0.12-0.17 

4.08-8.70 

6.38-8.69 

46.2-57.4 

1.73-2.27 

19.8-26.1 

 

Turf 0.07-

0.09 

1.31-1.67 

14.9-18.9 

1.21-1.57 

13.9-18.1 

<0.12-5.03 

1.06-3.31 

<.010 -0.28 

Nursery stock 

0.87-1.88 

9.86-20.59 

<0.32-0.69 

1.07-1.22 

16.7-36.1 

191-408 

<0.3-0.63 

3.79-8.08 

15.5-32.9 

178-379 

<0.10-5.65 

1.46-3.72 

<0.12-0.31