Table of Contents

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

II. Use and Usage.............................................................................................5

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

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

1. Risk Conclusions...................................................................................6

2. Tolerances..........................................................................................7

3. Human Incidents...................................................................................7

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

1. Environmental Fate and Exposure...............................................................8 

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

3. Overview of Ecological Risk Conclusions.....................................................8

4. Effects on Aquatic Organisms...................................................................8

5. Effects on Terrestrial Organisms................................................................9

6. Ecological Risk Management Conclusions for Non-listed Species........................10

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

 D. Endocrine Disruptor Screening Program............................................................11

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

V. Next Steps and Timeline..................................................................................13

A. Registration Review Decision........................................................................13

B. Implementation of Mitigation Measures............................................................13

Appendix A: Summary of Actions Taken for Triflumizole...........................................14

Appendix B: Triflumizole Label Table 1, Rate and RTI Label Mitigation..........................15

Appendix C: Triflumizole Label Table 2, Occupational exposure...................................16

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I. Introduction

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

Registration Review Decision for triflumizole (PC Code 128879, Case 7003) and is being issued 

pursuant to 40 CFR sections 155.56 and 155.58. A registration review decision is the Agency's 

determination on 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 final decision. Among other things, the interim registration review decision 

may 1) require new risk mitigation measures; 2) impose interim risk mitigation measures; 3)

identify data or information required to complete the review; and 4) include schedules for 

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

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

public docket (EPA-HQ-OPP-2008-0657) 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 re-evaluates pesticides to make sure that as these changes 

occur and products in the marketplace can continue to be used safely. Information on this 

program is provided at www.epa.gov/oppsrrd1/registration_review/. 

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

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

it continues to meet the FIFRA standard for registration.

This document comprises the interim registration review decision for triflumizole. 

Triflumizole is a broad spectrum, systemic imidazole fungicide (Group 3) that inhibits ergosterol 

biosynthesis in fungi. Triflumizole is registered for use on a variety of agricultural crops, nonagricultural crops, and as a pre-plant seed treatment. Triflumizole is also registered for uses on 

residential/non-commercially grown apples, pears and grapes. Registered application methods 

for triflumizole include broadcast, foliar spray, root dip, soil drench, chemigation, and seed piece 

treatment. A Reregistration Eligibility Decision document (RED) for triflumizole was not 

completed because it was registered after 1984.

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

triflumizole (case 7003). The following highlights significant events that have occurred during 

the registration review of triflumizole:

• March 28, 2007 – Publication of triflumizole 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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• August 22, 2007 - Final Work Plan (FWP) for triflumizole was issued – 3 comments

were received during the 60-day comment period for the triflumizole PWP. These 

comments, which were addressed in the FWP, did not change the work plan or timeline 

set out in the PWP.

• September 26, 2008 – Generic Data Call-In (GDCI) for triflumizole issued.

• June 26, 2013 – The Agency published the Registration Review – Ecological Risk 

Assessment and Effects Determination of Triflumizole and the Triflumizole: Human 

Health Risk Assessment for Registration Review for a 60-day public comment period.

• August 26, 2013 – 60-day public comment period for Preliminary Risk Assessments 

closed. No comments were received.

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

Review Decision for a 60-day public comment period. One comment was received from 

the Center for Biological Diversity regarding the Agency’s obligations under the 

Endangered Species Act (ESA). 

• March 2014 – The Agency is now publishing the Triflumizole Interim Registration 

Review Decision. 

Additional information on triflumizole can be found in EPA’s public docket, EPA-HQ-OPP2006-0115, accessed at www.regulations.gov.

Comments Received from the Center for Biological Diversity

(EPA-HQ-OPP-2006-0115-0040)

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

consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the 

Services) on the registration review of triflumizole in accordance with the 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 

triflumizole on endangered and threatened (listed) species and their designated critical habitat 

for the triflumizole registration review. 

Response: EPA has reviewed the comments from CBD on the Triflumizole Proposed Interim 

Registration Review Decision 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 triflumizole in connection with the development of its final 

registration review decision for this pesticide. See Endangered Species Assessment on page 10 of 

this document for more information.

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II. Use and Usage

The Agency conducted a qualitative benefits assessment for triflumizole and some other 

demethylation inhibiting (DMI) fungicides in June 2014, which is available in the docket

(Qualitative Assessment of Benefits of Triflumizole and Other Demethylation Inhibiting 

Fungicides Used on Cherry, Apple, Hazelnut, Grape, Strawberry and Cucurbits). This 

assessment was conducted to better examine the characteristics and uses of triflumizole and to 

qualitatively assess its benefits and overall use patterns. As described in that document, 

triflumizole is a Group 3 DMI fungicide, sometimes referred to as sterol biosynthesis inhibitor 

(SBI). Triflumizole is registered for use on a variety of agricultural crops, including cherry, 

hazelnut, apple, grape, strawberry, cucurbit, hazelnut, leafy greens, hops, and papaya. It is also 

registered for use on a number of non-food crops including ornamentals in greenhouses/shade 

houses, interior scapes, and Christmas trees/conifers on nurseries and plantations. It is also 

registered for use as a pre-plant seed piece treatment on pineapples.

An updated Screening Level Usage Analysis (SLUA) for triflumizole was conducted in 

January 2013. SLUA usage data (2004-2011) show triflumizole is primarily used, in terms of 

pounds and/or acres treated, on cherry, hazelnut, apple, grape, strawberry, and cucurbits. In 

2011, approximately 93,000 lbs of triflumizole were applied. Apples account for the majority of 

usage, making up approximately 40,000 lbs active ingredient (a.i) annually, then grapes (20,000 

lbs. a.i./year), along with uses on cherries, grapes, and pears (each 10,000 lbs. a.i./year)

representing triflumizole’s other major uses (Triflumizole Screening Level Usage Analysis, 

January 30, 2013). The updated SLUA for triflumizole can be found in the triflumizole 

registration review docket (EPA-HQ-OPP-2006-0115) at www.regulations.gov.

DMI fungicides, including triflumizole, are classified by the Fungicide Resistance Action 

Committee as Group 3 fungicides. Group 3 fungicides in general are reportedly one of the most 

important group of fungicides because of their efficacy against economically significant 

pathogens. They reportedly play an integral role as a component of overall fungicide application 

programs that seek to limit the development of resistance to several different fungicide 

chemistries.

As described in the June 2014 qualitative benefits assessment, for the crops which 

triflumizole is commonly used, there are generally a few other DMI fungicides registered for the 

same uses. Because resistance to this group of fungicides has developed for some important 

diseases, use restrictions are recommended for all of the Group 3 fungicides. Triflumizole is 

used in disease management programs that alternate triflumizole with applications of other nonDMI fungicides in support of standard stewardship practices to assist in fungicide resistance 

management. Although there is a higher cost per acre for certain uses of triflumizole compared 

to other DMI fungicides, triflumizole was found to be used at a relatively higher percent crop 

treated. The higher cost and higher percent crop treated suggests benefits specific to the use of 

triflumizole. DMI fungicides in general have been shown to provide particular value in the 

control of major diseases such as powdery mildew on apple, cherry, grape, strawberry, and 

cucurbits (cantaloupe, squash, and watermelon) as well as in combating Eastern Filbert Blight in 

hazelnut production and apple scab.

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III. Scientific Assessments

A. Human Health Risk 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 risk assessment in 

support of the registration review of triflumizole. The most recent human health risk assessment 

was completed on May 2, 2012, and revised on June 5, 2014, to include updates to restricted 

entry intervals (REI) for grapes and hops. The human health risk assessment consists of updated 

acute and chronic dietary (food and drinking water), residential (handler and post-application), 

aggregate, and occupational (handler and post-application) exposure assessments. Risk estimates 

were below the Agency's level of concern (LOC) for all but two human health scenarios 

(occupational handler and post-application). For a detailed discussion, see the Triflumizole: 

Human Health Risk Assessment for Registration Review, June 5, 2014, in the public docket EPAHQ-OPP-2006-0115, which can be accessed on http://www.regulations.gov/. 

1. Risk Conclusions

Risk estimates for triflumizole exceed the Agency's level of concern (LOC) for the following 

two occupational scenarios using currently required personal protective equipment (PPE): longsleeved shirt, long plants, chemical resistant gloves, shoes, and socks -

• Occupational Handler- Application of sprays with open cab air blast equipment on 

apples, pears, and cherries; dermal margin of exposure (MOE) = 230 (target MOE = 300)

• Occupational Post-Application- Mechanically assisted harvesting for hops and girdling 

for grapes (table and raisin), REI 12 hours, dermal MOE = 200 (grapes, table and raisin), 

MOE = 270 (hops) (target MOE = 300).

To mitigate the identified occupational handler risks of concern, the technical registrant, 

Chemtura Corp., has agreed to amend its registrations and labels to incorporate a chemical 

resistant hat to the existing occupational handler PPE for the open cab air blast spray application 

scenario, which results in a revised MOE of 1,900, and is no longer a risk of concern.

For occupational post-application risks to workers engaged in girdling of grapes (table and 

raisin), Chemtura has agreed to extend the REI from 12 hours to 1 day (revised MOEs = 400). 

To address post-application worker risks for mechanically assisted harvesting of hops, the REI at 

which risks are no longer of concern is 3 days (revised MOEs = 330). However, because the PHI 

of 7 days (for hops) already on the label is greater than a 3-day REI, the PHI will provide 

sufficient protection for re-entry by occupational workers and therefore a 3-day REI for hops is 

not required. 

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2. Tolerances

Tolerances are currently established for residues of triflumizole, including its metabolites 

and degradates, in or on plants and livestock in 40 CFR § 180.476. Codex has not established 

Maximum Residue Limits (MRLs) for residues of triflumizole in/on various raw agricultural and 

processed commodities. Tolerance definitions and tolerance levels are harmonized between 

Canada and the U.S. which can be found in Appendix B of Triflumizole: Human Health Risk 

Assessment for Registration Review.

The following tolerance amendments are needed for triflumizole: (1) modify the residue 

definition for the tolerance expression for triflumizole in accordance with the current policy on 

tolerance definitions (described on pg. 3-4 of the Human Health Risk Assessment); and (2)

modify the tolerance levels for certain commodities (listed below) to reflect conclusions of a 

previous review but are not currently reflected in the 40 CFR 180.476 (D346779, W. Cutchin, 

10/1/08). 

The following tolerances will be deleted from 180.476(a)(1): apple, dry pomace; apple, 

wet pomace; grape, dried pomace; grape, raisin, waste; and grape, wet pomace. The commodity 

listed as “cilantro, leaves” will be changed to “coriander, leaves.” Also, the following tolerances 

will be deleted from 180.476(a)(2): cattle, meat; egg; goat, meat; hog, fat; hog, meat; hog, meat 

byproducts; horse, meat; milk; poultry, fat; poultry, meat; poultry, meat byproducts; and sheep, 

meat. Tolerance levels for the following commodities will be lowered from 0.5 to 0.10 ppm: fat 

of cattle, sheep, goat, and horse. Tolerance levels for the following commodities will be lowered 

from 0.5 to 0.20 ppm: meat byproducts of cattle, sheep, goat, and horse.

3. Human Incidents

A small number of minor human health incidents have been reported to the Agency 

involving triflumizole. From January 1, 2006 to August 5, 2014, there were 3 incidents reported 

to the Office of Pesticide Program’s Main Incident Database System. These incidents were 

classified as moderate severity. A query of SENSOR-Pesticides 2006-2010 identifies a total of 

23 cases (2 moderate severity and 21 low severity). Of these cases, 5 were single active

ingredient cases and all 5 were low severity. Based on the continued low frequency and severity 

of incident cases reported for triflumizole, there does not appear to be a concern with the current 

uses of triflumizole when used as directed by labels. The Agency will continue to monitor the 

incident information and if a concern is triggered, additional analysis will be conducted. For 

more information please refer to Triflumizole: Tier I Review of Human Incidents for Preliminary 

Risk Assessment, August 19, 2014.

B. Environmental Assessment

The risk assessment supporting this Interim Registration Review Decision evaluates risks 

to species that are not subject to the ESA and provides a screening level assessment for potential 

risks to listed species under ESA. A summary of the Agency’s environmental risk assessment

for triflumizole is presented below. For detailed discussions of all aspects of the environmental 

risk assessment, see the Registration Review – Ecological Risk Assessment and Effects 

7
Determination of Triflumizole and Refinements to the Triflumizole Preliminary Risk Assessment 

in Support of Registration Review, published on June 26, 2013 in the public docket EPA-HQOPP-2006-0115-0030, which can be accessed on http://www.regulations.gov/. 

1. Environmental Fate and Exposure

Triflumizole is not likely be persistent under most environmental conditions and is 

unlikely to be very mobile (except for in sandy soils with low organic matter). Triflumizole’s 

moderate adsorption characteristics suggests that triflumizole has a low potential to reach 

groundwater. Triflumizole will reach surface water in both the dissolved form and sorbed onto 

soils and organic material for several weeks following application.

The major pathways of triflumizole degradation are hydrolysis under acidic and alkaline 

conditions, anaerobic aquatic metabolism, and to a lesser extent aerobic soil metabolism. Halflives varied depending on environment conditions at the application site. 

2. Ecological Risk Characterization

To estimate potential ecological risk, EPA integrates the results of exposure and 

ecotoxicity studies using the risk quotient method. Risk quotients (RQs) are calculated by 

dividing acute and chronic EECs by ecotoxicity values for various wildlife and plant species. 

RQs are then compared to levels of concern (LOCs) and when the RQ exceeds the LOC for a 

particular category, the Agency evaluates the potential for a risk of concern to that category. 

Risk characterization provides further information about potential adverse effects and the 

possible impact of those effects by considering the fate of the chemical and its degradates in the 

environment, organisms potentially at risk, and the nature of the effects observed. 

3. Overview of Ecological Risk Conclusions

Conservative assumptions were made in the ecological risk assessment for triflumizole to 

estimate the ecological risks (e.g., risk estimates are based on the maximum application rates and 

number of applications rather than typical rates). For non-listed species, chronic RQs for 

mammals exceeded the LOCs for all registered uses of triflumizole. For all other non-listed taxa, 

RQs were below target LOCs for all uses and there are no risks of concern. 

4. Effects on Aquatic Organisms

The primary route of exposure to aquatic organisms is potential runoff and spray drift 

from labeled applications of triflumizole. Acute and chronic risk estimates were below the LOC 

for non-listed freshwater and estuarine/marine fish (surrogates for aquatic-phase amphibians), 

freshwater and estuarine/marine invertebrates, and aquatic vascular and non-vascular plants for 

all uses of triflumizole. Therefore, no risks of concern are anticipated for non-listed aquatic 

organisms based on the registered uses of triflumizole. 

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5. Effects on Terrestrial Organisms

Mammals

There are no acute risks of concern to non-listed mammals from the registered uses of 

triflumizole based on calculated RQs. However, RQs exceed the target LOCs for non-listed 

mammals on a chronic basis for all uses. The June 4, 2013 Ecological Risk Assessment and 

effects Determination of Triflumizole was conducted using an incorrect mammalian endpoint

(NOEC = < 30 mg/kg diet; NOAEL = <1.5 mg/kg bw). The risk assessment has been updated to 

include the correct chronic mammalian reproduction endpoint (NOEC = 70 mg/kg diet; NOAEL 

= 3.5 mg/kg bw). These updates can be found in Refinements to the Triflumizole Preliminary 

Risk Assessment in Support of Registration Review, May 8, 2014 posted in the docket. The use of 

this revised endpoint decreased the overall RQs but they still exceed the target LOC for chronic 

mammalian exposure. Using the correct mammalian endpoint, the chronic RQs in the screening 

level risk assessment ranged from 0.1 (leafy greens) to 74.42 (ornamentals).

Chronic Mammalian Risk Characterization

Conservative assumptions in the screening level risk assessment include the use of (1) 

maximum labeled rates; (2) upper bound Kenaga values (95th percentile) to estimate 

environmental concentrations (EECs) for mammals; and (3) 100% of a mammalian diet is 

assumed to come from one food type (on a treated field). To better characterize chronic risks to 

non-listed mammals, the following refinements were made to the risk assessment: 

(1) Incorporated average Kenaga EECs (50th percentile), which may more accurately 

capture long-term concentrations that are expected to be found in the environment. In 

addition, the average provides additional information on the frequency, likelihood, and 

magnitude of exposure for varied situations. The Kenaga nomograph is based on a large 

set of field residue data (not triflumizole specific) and is incorporated in to the terrestrial 

residue exposure model (T-REX), which was used to assess chronic mammalian exposure 

to triflumizole.

(2) The screening level assessment used maximum labeled rates as a conservative screen. 

Alternative application scenarios were assessed using estimated average maximum 

application rates, average number of applications, and average application intervals. 

Based on available use and extension information, the Agency estimated average or 

typical use rates which were incorporated and may more accurately represent what is 

generally used by growers. 

When the average Kenaga values and typical rates are used, the RQs are decreased 

significantly. For cherries RQs decreased from 58.54 to 20.54. For apples/pears the RQs 

decreased from 41.16 to 14.58.

For more information regarding the revisions and additional characterization of 

mammalian risk see the Refinements to the Triflumizole Preliminary Risk Assessment in Support 

of Registration Review.

9
Birds, Terrestrial Plants, Terrestrial Invertebrates

There are no acute or chronic risks of concern to non-listed birds (and to reptiles and 

terrestrial phase amphibians for which birds serve as surrogates); terrestrial plants; and terrestrial 

invertebrates from the registered uses of triflumizole based on calculated RQs.

6. Ecological Risk Management Conclusions for Non-Listed Species 

The ecological risk assessment for triflumizole identified RQs that exceed the chronic 

LOCs for non-listed mammals for all uses (RQs in the screening level risk assessment range 

from 0.1 to 74.42). To mitigate the identified risks, Chemtura (the technical registrant) has 

voluntarily agreed to (1) increase the re-treatment interval (RTI) to allow for degradation; (2) 

reduce the maximum number of applications per year; and, (3) reduce the maximum application 

rates for several crops. As a result of these changes RQs are reduced; for example, cherries go 

from an RQ of 58 to 29 with the agreed mitigation. These mitigation measures are in accordance 

with standard fungicide resistance management practices. See table 1 on pg. 17 of this document 

for a detailed description of the agreed upon mitigation. EPA is working with the triflumizole 

technical registrant to amend their labels accordingly. Amended labels for technical and end-use 

products registered must be submitted to the Agency for approval within 60 days of the 

publication of the Interim Registration Review Decision for triflumizole.

The Agency does not believe triflumizole poses an unreasonable risk to mammals. 

Although RQs exceed the chronic mammalian LOCs for many uses, even when the proposed

label changes are made to mitigate risk, the Agency believes that ecological risk from 

triflumizole use is not expected for the following reasons: (1) as is described above, the 

screening level risk assessment is conservative in nature. Refinements to the assessment likely 

capture a more realistic estimate of exposure and significantly reduce the chronic mammalian 

RQ exceedances; (2) the anticipated label changes (mitigation) to the various maximum 

applications rates, RTIs, and total number of annual applications represent significant reductions 

to the chronic mammalian risk picture; and (3) in addition, the Agency conducted a qualitative 

benefits assessment (as described in the “Use and Usage Section” of this Interim Decision) and 

determined that triflumizole plays an important role in fungicide resistance management 

practices for controlling major disease pressure. 

C. 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 

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

Risks to Endangered and Threatened Species from Pesticides. 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. EPA will address concerns specific to triflumizole in 

connection with the development of its final registration review decision for triflumizole. 

1 http://www.nap.edu/catalog.php?record_id=18344

10

 
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. 2

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 triflumizole 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 triflumizole 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 triflumizole as part of completing this registration review.

D. Endocrine Disruption 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 triflumizole, 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), 

triflumizole 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 

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

11

 
the potential of a triflumizole 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, which included triflumizole, was published on June 14, 

20133 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.4 

In this Interim Registration Review Decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of triflumizole. 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 triflumizole. Except for the EDSP and ESA 

components of the triflumizole registration review case, the Agency has made the following 

interim decision: (1) changes are required to triflumizole products (reduction of maximum 

number of applications; reduction in maximum application rate; increase re-treatment intervals)

registered for the following crops to address risk concerns to mammals on a chronic basis: pome 

fruit crop group 11-10, cherry, grape, strawberry, cucurbits, brassica leafy greens, head & stem 

brassica, leafy greens (e.g. spinach), filbert/hazelnut, hops, papaya, mango, pineapple (dip 

application) and ornamentals; and (2) the following changes are required to mitigate risks to 

occupational handlers and post-application workers: (a) the requirement of a chemical resistant 

hat for applications using open cab air blast equipment; and (b) increase the REI for table and 

raisin grapes to 1 day. The Agency has been working with the single technical and end-use 

product registrant for triflumizole, Chemtura Corporation, who has voluntarily agreed to revise 

all affected labels accordingly.

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

associated with the EDSP screening of triflumizole. Before completing this Registration 

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

completing this Registration Review, the Agency will conduct an ecological risk assessment to 

address the Agency’s obligations under both the ESA and FIFRA. While the risk assessment 

supporting this Interim Registration Review Decision evaluates risks to species that are not 

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

chemicals.

4 http://www.epa.gov/endo/

12

 
subject to the ESA, EPA is still in the process of conducting a risk assessment for listed species 

and their designated critical habitats for triflumizole. In this Interim Decision, therefore, EPA 

has not completed effects determinations for listed species associated with the registered uses of 

triflumizole. The Agency is issuing an Interim Registration Review Decision pending 

completion of the ESA and EDSP assessments.

V. Next Steps and Timeline

A. Registration Review Decision

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

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

B. Implementation of Mitigation Measures

EPA is requiring the registrant to submit proposed amended labels that include the 

agreed-upon risk mitigation, described in Appendices A, B and C below, to the Agency for 

approval within 60 days from the date of issuance of this Interim Registration Review Decision.

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Docket Number EPA-HQ-OPP-2006-0115

www.regulations.gov

Appendix A: Summary of Actions Taken for Triflumizole

Registration Review Case#: 7003

PC Code: 128879

Chemical Type: Systemic broad spectrum fungicide

Chemical Family: Imidazole (group 3) fungicide

Mode of Action: Ergosterol biosynthesis inhibitor in fungi

Affected Population(s) Source of 

Exposure

Route of Exposure Duration of 

Exposure

Risk of Concern Action(s) Taken

 Non-listed 

mammals

 Direct 

application

 Spray drift

 Runoff

 Ingestion  Chronic  Direct  See Appendix C

 Occupational 

handlers

 Direct 

application to 

crop

 Dermal  Short-

/Intermediateterm

 Direct  In addition to current labeled 

PPE requirements, chemical 

resistant hat during open cab air 

blast applications to grapes, 

apples, pear, and cherries.

 Occupational postapplication 

workers

 Residues on 

site of 

treatment

 Dermal  Short-term  Direct  Increase REI from 12 hours to 

1 day for girdling grapes (table 

and raisin). 
Appendix B: Triflumizole Label Table 1, Rate and RTI Label Mitigation (grayed rows denote label mitigation)

Procure Crops

Max. Rate Procure 

480SC per 

Application 

(lbs.ai./A)

Max. 

no. of 

Appls. 

/ Crop 

/ Yr.

Max. Appl. Rate 

Procure 480SC 

per Acre per 

Year (lbs. 

ai./A/yr.)

Min. 

RTI 

(days) Label Mitigation Comments

Pome Fruit Crop Group 11-10

(Apple, pear)

16 fl.ozs. (0.5) 4 64 fl.ozs. (2.0) 7 Current Label Scenario 

16 fl.ozs. (0.5) 4 56 fl.ozs. (1.75) 14/21/14 1st app/14 day RTI/2nd app/21 day RTI/3rd app/14 day RTI

Cherry 16 fl.ozs. (0.5) 6 96 fl.ozs. (3.0) 7 Current Label Scenario

16 fl.ozs. (0.5) 4 56 fl.ozs. (1.75) 14/21/14 1st app/14 day RTI/2nd app/21 day RTI/3rd app/14 day RTI

Curcurbits 8 fl.ozs. (0.25) 5 40 fl.ozs. (1.25) 7 Current Label Scenario

6-8 fl.ozs. (0.1875-

0.25)

3-4 24 fl.ozs. (0.75) 7 3 applications @ 8 fl.ozs. (0.25 lbs. ai.)/A or 4 applications 

@ 6 fl.ozs. (0.1875 lbs.ai.)/A

Brassica Leafy Greens 8 fl.ozs. (0.25) 3 18 fl.ozs. (0.563) 14 Current Label Scenario, 3rd app made at reduced rate

8 fl.ozs. (0.25) 2 16 fl.ozs. (0.5) 14 2 applications @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 days

Head & Stem Brassica 8 fl.ozs. (0.25) 3 18 fl.ozs. (0.563) 14 Current Label Scenario, 3rd app made at reduced rate

8 fl.ozs. (0.25) 2 16 fl.ozs. (0.5) 14 2 applications @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 days

Leafy Greens (ex. spinach) 8 fl.ozs. (0.25) 3 18 fl.ozs. (0.563) 14 Current Label Scenario, 3rd app made at reduced rate

8 fl.ozs. (0.25) 2 16 fl.ozs. (0.5) 14 2 applications @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 days

Filbert / Hazelnut 6 fl ozs. (0.1875) 4 24 fl.ozs. (0.75) 10 Current Label Scenario 

6 fl ozs. (0.1875) 2 12 fl.ozs. (0.375) 10 2 applications @ 6 fl.ozs. (0.1875 lbs.ai.)/A @ 10 days

Hops 12 fl ozs. (0.375) 3 36 fl. ozs. (1.125) 14 Current Label Scenario

12 fl ozs. (0.375) 2 24 fl.ozs. (0.75) 14 2 applications @ 12 fl.ozs. (0.375 lbs.ai.)/A @ 14 days

Papaya, Mango 10 fl.ozs. (0.3125) 3 24 fl.ozs. (0.75) 14 Current Label Scenario, 3rd app made at reduced rate

8 fl.ozs. (0.25) 1 8 fl.ozs. (0.25) NA

Ornamentals (Tguard SC) 64 fl.ozs. (2.0) NS > 96 fl.ozs. (3.0) 7 Current Label Scenario

8-16 fl.ozs. (0.5) 2-4 32 fl.ozs. (1.0) 14 2 applications @ 16 fl.ozs. (0.5 lbs.ai.)/A @ 14 days or 4 

appls. @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 days

Ornamentals (Tguard SC/LS) 32 fl.ozs. (1.0) NS 96 fl.ozs. (3.0) 7 Current Label Scenario

8-16 fl.ozs. (0.5) 2-4 32 fl.ozs. (1.0) 14 2 applications @ 16 fl.ozs. (0.5 lbs.ai.)/A @ 14 days or 4 

appls. @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 days

Denotes label mitigation

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Appendix C: Triflumizole Label Table 2, Occupational Exposure

Triflumizole Labeled 

Crops Current PPE New PPE Current REI New REI 

Pome Fruit Crop Group 

11-10

(Apple, pear)

Long-sleeved shirt & long pants; 

chemical resistant gloves made of 

any waterproof materials; shoes 

plus socks

In addition to current PPE require: 

“chemical resistant hat for 

applicators using open cab air blast 

equipment”

12 hours No change to REI

Cherry Long-sleeved shirt & long pants; 

chemical resistant gloves made of 

any waterproof materials; shoes 

plus socks

In addition to current PPE require:

“chemical resistant hat for 

applicators using open cab air blast 

equipment”

12 hours No change to REI

Grape Long-sleeved shirt & long pants; 

chemical resistant gloves made of 

any waterproof materials; shoes 

plus socks

No change to PPE

12 hours

Maintain 12 hours for 

wine grapes 

w/addition of:

“1 day REI for 

girdling of table and 

raisin grapes”

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