Table of Contents

Contents 

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

II. Use and Usage/Background. ...................................................................................................6

III. Scientific Assessments........................................................................................................... 6

A. Human Health Assessment .................................................................................................... 6

Hazard Characterization and Risk .......................................................................................... 6

Food Tolerances.......................................................................................................................7

Human Incidents..................................................................................................................... 8

B. Environmental Assessment ................................................................................................... 8

Ecological Risk Characterization............................................................................................ 8

Ecological Risk Assessment Uncertainties............................................................................10

Ecological Incidents.............................................................................................................. 11

Endangered Species Assessment .......................................................................................... 11

C. Endocrine Disruptor Screening Program ............................................................................. 12

IV. Interim Registration Review Decision...........................................................................13

V. Next Steps and Timeline....................................................................................................17

 A. Registration Review Decision ..............................................................................................17

 B. Implementation of Mitigation Measures........................................................................17

Appendix A: Summary of Proposed Actions Taken for Flutolanil ............................................18

Appendix B: Flutolanil Label Table ...........................................................................................19

Appendix C: Risk Quotient Ranges............................................................................................20

2
I. Introduction

This document is the Environmental Protection Agency’s (EPA or the Agency) 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, an interim registration review decision before completing a registration review. 

Among other things, the 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.

3
• 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. One comment was received from the Center for Biological Diversity (CBD) on 

the ecological risk assessment regarding consultation requirements under the Endangered 

Species Act (ESA), which did not result in any revisions to the assessment. 

• September 2014 – The Agency published the Flutolanil Proposed Interim Registration

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

comment period. One comment was received from the CBD, similar to the comment 

received on the draft ecological risk assessment. The comment is summarized below

with the Agency’s response. 

Comment: The Center for Biological Diversity’s (CBD) comments focus on the EPA’s duty 

to consult with the US. Fish and Wildlife Service and the National Marine Fisheries 

Service (the Services) on the registration review of flutolanil in accordance with the 

Endangered Species Act (ESA). The CBD comments mention various aspects of the risk 

assessment process, including use of the best available data to develop endangered 

species risk assessments, and evaluation of effects on endangered and threatened species 

and their designated critical habitat. CBD also expresses concern regarding the rigor of 

the Agency's preliminary determinations regarding the effects of flutolanil on 

endangered and threatened (listed) species and their designated critical habitat for the 

flutolanil registration review.

Response: EPA has reviewed the comments from CBD on the Proposed Registration Review 

Decision for flutolanil and plans to address many of the concerns raised by CBD as part 

of the implementation plan for assessing the risks of pesticides to listed species based on 

the recommendations of the April 2013 National Academy of Sciences (NAS) report. 

EPA will address concerns specific to flutolanil in connection with the development of its 

final registration review decision for flutolanil.

In November 2013, the EPA, along with the Services and the USDA, released a summary 

of their joint Interim Approaches for assessing risks to endangered and threatened (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 

4
scientific differences between the EPA and the Services. The NAS report1 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 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. The agencies also held stakeholder 

workshops in April and October 2014, allowing additional opportunities for stakeholders 

to comment on the Interim Approaches. Additional workshops are planned to enhance 

stakeholder involvement. 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 Report2

, 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 risk assessment supporting this Interim Decision for 

flutolanil does not include a complete ESA analysis, including effects determinations for 

specific listed species or designated critical habitat. This screening-level risk assessment 

determined the potential effects of flutolanil on all taxa of non-target wildlife and plants, 

assuming that listed species and their 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. 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.

• March 2015 - The Agency is now publishing the Flutolanil Interim Registration Review 

Decision in EPA’s public docket, EPA-HQ-OPP- 2008-0148, accessed at 

www.regulations.gov.

1 http://www.nap.edu/catalog/18344

2 http://www.epa.gov/espp/2013/nas.html

5

 
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.) and 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 a

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

6
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 and 

post-application exposure assessments, occupational handler and post-application exposure 

assessments, 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.

7
Human Incidents

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 received one comment on the risk assessment from the Center for Biological 

Diversity (CBD) regarding consultation requirements under the Endangered Species Act (ESA), 

which did not result in any revisions to the 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 

8
more detail below. The range of risk quotients (RQ’s) for different scenarios are provided for 

each taxon in Appendix C.

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 showing 

9
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. However, data are not available to evaluate the potential effects to larvae, or 

chronic risk to adult insects.

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 potentially 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) and the 

Pesticides in Flooded Applications Model (PFAM) 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 

10
a.i./acre for rice. Also, since the chemical shows medium to high pest resistance (as indicated by 

Fungicide Resistance Action Committee for chemicals in Group 7), it may not be applied every 

year to rice as simulated in the exposure model.

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 Avian Incident Monitoring System database maintained by the American 

Bird Conservancy, of all years of available data up until October 2013.

Endangered Species Assessment

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency 

will evaluate risks to federally listed threatened and endangered (listed) species from registered 

uses of pesticides in accordance with the Joint Interim Approaches developed to implement the 

11
recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks 

to Endangered and Threatened Species from Pesticides. The NAS report3 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 ESA and FIFRA. EPA will address concerns specific to flutolanil in connection with the 

development of its final registration review decision for flutolanil. 

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries 

Services (the Services), and the U.S. Department of Agriculture released a white paper containing a 

summary of their joint Interim Approaches for assessing risks to listed species from pesticides.

These Interim Approaches were developed jointly by the agencies in response to the 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. Details of the joint 

Interim Approaches are contained in the November 1, 2013 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.4

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 Interim Registration Review Decision 

for flutolanil does not contain a complete ESA analysis, including effects determinations for 

specific listed species or designated critical habitat. While the agencies continue to develop a 

common method for ESA analysis, the preliminary risk assessment for the registration review of 

flutolanil describes the level of ESA analysis completed for this particular registration review case. 

This 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. Once the agencies have fully developed and implemented the scientific methods 

necessary to complete risk assessments for listed species and their designated critical habitats, these 

methods will be applied to subsequent analyses of 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

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 

3 http://www.nap.edu/catalog/18344 4 http://www.epa.gov/espp/2013/nas.html

12

 
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 during 2015.

In this 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. Interim Registration Review Decision

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

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/

13
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%. 

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 LOC 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 RQs 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 and 

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 twice the LOC for most of these uses, and so our modeling suggests 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 would represent a very small portion of potentially exposed birds.

15
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 

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. In addition, risk to pollinators has not been assessed. 

The Agency is issuing an interim registration review decision pending the evaluation of 

potential endocrine disruptor risk, consultation with the Services, and an assessment of risk to 

pollinators. 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. 

16
The Agency is issuing an Interim Registration Review Decision pending completion of the ESA 

and EDSP assessments, as well as an assessment of non-target exposure to pollinators. As the 

Agency works toward implementing its Guidance for Assessing Pesticide Risks to Bees

http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance, additional data 

may be required for flutolanil to assess non-target exposure to bees.

V. Next Steps and Timeline 

A. Registration Review Decision 

A final decision on the flutolanil registration review case will occur after an ESA and 

EDSP FFDCA section 408(p) determination have been made.

B. Implementation of Mitigation Measures

Registrants will need to submit proposed amended labels that include the agreed-upon end 

use product risk mitigation and submit them to the Agency within 60 days of issuance of the 

Interim Registration Review Decision. The mitigation measures and label amendments are 

described in Appendix A and B.

17
Appendix A: Summary of Proposed Actions Taken for Flutolanil

Registration Review Case#: 7010

PC Code: 128975

Chemical Type: Fungicide

Chemical 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(s) Taken Comments

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

Dermal absorption

Acute

Chronic

Acute Toxicity

Chronic toxicity ‐ growth Buffer

Specify Medium or 

larger droplet size

Restrict number of 

applications

Buffer on Turf 

uses for estuary

and marine 

habitats.

Medium‐large 

droplet size to 

reduce spray 

drift to aquatic 

habitats on turf, 

ornamental, 

and aerial 

peanut 

applications.

Restrict 

applications per 

year to 

ornamental 

plantings.

Aquatic Invertebrates

estuarine/marine

Water (direct contact, non‐dietary) Ingestion

Dermal absorption

Acute

Chronic

Acute Toxicity

Chronic toxicity ‐

reproduction

18
Appendix B: Flutolanil Label Table

Summary of Proposed Labeling Changes for Flutolanil Uses

Description Labeling Language for Flutolanil Turf and Ornamental End Use Products Placement on Label

Use Restrictions –

Products labeled for turf 

and ornamentals

“For use rates over 3 oz. per 1000 sq ft, do not apply within 100 feet of any estuary or marine habitat or within 100 feet 

of any ditches, drainage tiles, or other waterways that drain directly into (within 1⁄2 mile) estuaries and marine habitats. 

“Apply no more than a combined total of 6 oz. per 1000 square feet as a broadcast application during a single growing 

season” or similar statement 

Use 

Restrictions 

section 

following 

Directions for use 

section

Directions for UseProducts labeled for turf 

and ornamentals

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

After General

Information on 

Greenhouse/Saran 

and shade

house/Outdoor

Container/Field 

Grown Ornamental 

Nursery Stock

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

have more stringent regulations, they must be observed. Avoiding spray drift is the responsibility of the applicator or 

grower. To reduce the potential for drift, the application equipment must be set to apply Medium or larger droplets (i.e. 

ASABE Standard 572) with corresponding spray pressure. Use high flow rate nozzles to apply the highest practical 

spray volume, using the appropriate droplet size to ensure adequate canopy distribution, coverage, and penetration. 

With most nozzle types, narrow spray angles produce larger droplets. Follow the nozzle manufacturer’s directions on 

pressure, orientation, spray volume, etc., in order to minimize drift and optimize coverage and control.”

Directions for Use

Description Labeling Language for Flutolanil End Use Peanut Products with aerial application

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

have more stringent regulations, they must be observed. Avoiding spray drift is the responsibility of the applicator or 

grower. To reduce the potential for drift, the application equipment must be set to apply Medium or larger droplets (i.e. 

ASABE Standard 572) with corresponding spray pressure. Use high flow rate nozzles to apply the highest practical 

spray volume, using the appropriate droplet size to ensure adequate canopy distribution, coverage, and penetration. With 

most nozzle types, narrow spray angles produce larger droplets. Follow the nozzle manufacturer’s directions on 

pressure, orientation, spray volume, etc., in order to minimize drift and optimize coverage and control.”

Directions for Use 

19
Appendix C: Risk Quotient Ranges

FW fish FW

invertebrates

E/M Fish3 E/M

invertebrates

FW benthic 

invertebrates

E/M benthic 

invertebrates

Birds Mammals Terrestrial 

plants

Nonvascular 

aquatic 

plants

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

Chronic RQ

Listed Acute

Non-listed

Acute

Non-Listed

Acute

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

>1.04-

1.45

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

1.09-

2.71

1.01

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

<1.04-

3.10

1.09-

2.72

1.01 >2.88-

5.86

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 chronic fish study

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 with a nondefinitive acute toxicity endpoint.

20