Docket Number EPA-HQ-OPP-2006-0115 

www.regulations.gov 

Triflumizole 

Proposed Interim Registration Review Decision 

Case Number 7003 

September 2014 

Approved by: Gl^-^a^d- P ^LCJUTU ^ , "^Ip 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 

Date: 9' n-.^c^'-f 
2 

Table of Contents 

Contents

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

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

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

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

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

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

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

B. Ecological ............................................................................................................................. 7

4. Environmental Fate and Exposure ................................................................................ 8

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

6. Overview of Ecological Risk Conclusions ................................................................... 8

7. Effects on Terrestrial Organisms .................................................................................. 9

8. Effects on Aquatic Organisms .................................................................................... 10

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

10. Ecological Risk Management Conclusions for Non-Listed Species .......................... 10

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

 D. Endocrine Disruptor Screening Program .............................................................................. 12

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

V. Next Steps and Timeline ....................................................................................................... 14

 A. Interim Registration Review Decision .................................................................................. 14

 B. Implementation of Mitigation Measures ............................................................................... 14

Appendix A: Summary of Actions Taken for Triflumizole ......................................................... 15

Appendix B: Triflumizole Label Table 1, Proposed Rate and RTI Label Mitigation ................. 16

Appendix C: Triflumizole Label Table 2, Occupational exposure .............................................. 17
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I. Introduction 

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

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 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: 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 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. 

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, non-agricultural crops, and as a pre-plant seed treatment. 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 is now publishing the Triflumizole Proposed Interim 

Registration Review Decision, dated September 2014 in docket number EPA-HQ-OPP2006-0115 for a 60-day public comment period.

Additional information on triflumizole can be found in EPA’s public docket, EPA-HQ-OPP2006-0115, accessed at www.regulations.gov. 
5 

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 

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 were above the Agency's level of concern (LOC) for the 

following two occupational scenarios using currently required personal protective equipment 

(PPE): long-sleeved 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 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. 

For occupational post-application 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 harvesting hops, the REI should be 3 days (revised MOEs = 330). 

However, to address identified ecological risks of concern for hops, the registrant has agreed to 

increase the Post-Harvest Interval (PHI) to 7 days. Because the PHI of 7 days (for hops) 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) the residue 

definition for the tolerance expression for triflumizole should be modified in accordance with the 

current policy on tolerance definitions (described on pg. 3-4 of the Human Health Risk 

Assessment); and (2) the tolerance levels for certain commodities (listed below) should reflect 

recommendations made in 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 should 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 suggest concern from 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. Ecological 

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

used the most updated Agency science policies and risk assessment methodologies to prepare a 

risk assessment in support of the registration review of triflumizole. For detailed discussions of 

all aspects of the environmental risk assessment see Registration Review – Ecological Risk 

Assessment and Effects Determination of Triflumizole and Refinements to the Triflumizole 

Preliminary Risk Assessment in Support of Registration Review dated May 8, 2014 available in 
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the public docket EPA-HQ-OPP-2006-0115, which can be accessed at 

http://www.regulations.gov/. 

The Agency also completed a screening-level endangered and threatened (listed) species 

assessment for triflumizole and identified potential risks to several taxa: mammals, birds, 

reptiles, land-phase amphibians, freshwater fish and estuarine/marine invertebrates. The Agency 

is currently working with its federal counterparts and other stakeholders to implement an interim 

approach for assessing potential risk to listed species and their designated critical habitats. Once 

the scientific methods necessary to complete risk assessments for listed species and their 

designated critical habitats are finalized, the Agency will complete its endangered species 

assessment for triflumizole. As such, only screening-level risks to listed species will be 

described here. Risks to listed species will not be characterized herein. 

4. 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. 

5. 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. 

6. 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 were above 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. 
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7. 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). 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 & Mitigation 

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. 
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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. 

8. 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. 

9. Ecological Incidents 

A review of the ecological incident information system (EIIS) and the avian monitoring 

information system (AIMS), which is maintained by the American Bird Conservancy, was 

conducted on May 2, 2012 for triflumizole. Neither the EIIS nor the AIMS database identified 

any ecological incidents associated with the use of triflumizole. 

10. Ecological Risk Management Conclusions for Non-Listed Species 

The draft 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 proposed 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 
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benefits assessment (as described in the “Use and Usage Section” of this Proposed Interim 

Decision) and determined that triflumizole plays an important role in fungicide resistance 

management practices for controlling major disease pressure. 

C. Endangered Species Assessment 

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

assessment to address the Agency’s obligations under both the Endangered Species Act (ESA) 

and FIFRA. While the risk assessment supporting this Proposed Interim Registration Review 

Decision evaluates risks to species that are not subject to the ESA, EPA is still in the process of 

conducting a risk assessment for endangered and threatened (listed) species and their designated 

critical habitats for triflumizole. In this Proposed Interim Registration Review Decision, 

therefore, EPA has not completed effects determinations for listed species associated with the 

registered uses of triflumizole. 

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

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

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

to listed species from pesticides. The “Interim Approaches for National-Level Pesticide 

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

of Sciences April 2013 Report” (Interim Approaches), dated November 1, 2013, were developed 

jointly by the agencies in response to the National Academy of Sciences’ (NAS) 

recommendations and reflect a common approach to risk assessment shared by the agencies as a 

way of addressing scientific differences between the EPA and the Services. The NAS report

outlines recommendations on specific scientific and technical issues related to the development 

of pesticide risk assessments that EPA and the Services must conduct in connection with their 

obligations under the Endangered Species Act (ESA) and FIFRA. 

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

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

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

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

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

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

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

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

contained in the Interim Approaches white paper. 

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

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

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

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

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

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

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

wildlife and plants that assumes for the sake of the assessment that listed species and designated 
12 

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

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

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

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

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

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

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

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

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

completing this registration review. 

D. 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 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 

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, 

20131

 and includes some pesticides scheduled for Registration Review and chemicals found in 

 

1

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

chemicals. 
13 

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

 

In this Proposed 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. Proposed Interim Registration Review Decision 

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

Proposed Interim Registration Review Decision. Except for the EDSP and Endangered Species 

Act (ESA) components of the triflumizole registration review case, the Agency has made the 

following proposed interim decision: (1) changes are required to triflumizole products (reduction 

of maximum number of applications; reduction in maximum application rate; increase retreatment 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: (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 and increase the REI to 3 days for mechanical harvesting of hops. 

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 Endangered Species Act (ESA) and FIFRA. 

While the risk assessment supporting this Proposed Interim Registration Review Decision 

evaluates risks to species that are not subject to the ESA, EPA is still in the process of 

conducting a risk assessment for endangered and threatened (listed) species and their designated 

critical habitats for triflumizole. In this Proposed Interim Registration Review Decision, 

therefore, EPA has not completed effects determinations for listed species associated with the 

registered uses of triflumizole. The Agency is issuing a Proposed Interim Registration Review 

Decision pending completion of the ESA and EDSP assessments. 

 

2 http://www.epa.gov/endo/
14 

V. Next Steps and Timeline 

A. Interim Registration Review Decision 

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

Registration Review Decision for triflumizole and allow a 60-day comment period. If there are 

no significant comments or additional information submitted to the docket during the comment 

period that leads the Agency to change its decision, EPA may issue an Interim Registration 

Review Decision for triflumizole (case 7003). However, a final decision for triflumizole may be 

issued without issuing an interim decision. A final decision on the triflumizole registration 

review case will occur after ESA and EDSP FFDCA section 408(p) determinations have been 

made. 

B. Implementation of Mitigation Measures 

Within 60 days following issuance of the final Interim Registration Review Decision, 

registrants will be required to submit to the Agency for review and approval proposed amended 

labels. The mitigation measures and required label amendments are described in Appendices A 

and B below.
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 Trinexapac-ethyl Type: Systemic broad spectrum fungicide Trinexapac-ethyl 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 Acti

 Non-listed mammals 

 Direct 

application 

 Spray drift 

 Runoff 

 Ingestion 

 Chronic 

 Direct 

 See Append

 Occupational handlers 

 Direct 

application to crop 

 Dermal 

 Short-

/Intermediate-term 

 Direct 

 In addition 

requirementhat during oapplications pear, and ch

 Occupational postapplication workers 

 Residues on 

site of treatment 

 Dermal 

 Short-term

 Direct 

 Increase RE

mechanicall1 day for giraisin). 

 Pre-harvest 

days for hopREI. 

 All other lab

maintain RE
Appendix B: Triflumizole Label Table 1, Proposed Rate and RTI 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 

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 

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 

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

Brassica Leafy Greens 8 fl.ozs. (0.25) 2.25 18 fl.ozs. (0.563) 14 Current Label Scenario 

8 fl.ozs. (0.25) 2 16 fl.ozs. (0.5) 14 2 applications @ 8 fl.ozs. (0.25 

Head & Stem Brassica 8 fl.ozs. (0.25) 2.25 18 fl.ozs. (0.563) 14 Current Label Scenario 

8 fl.ozs. (0.25) 2 16 fl.ozs. (0.5) 14 2 applications @ 8 fl.ozs. (0.25 

Leafy Greens (ex. spinach) 8 fl.ozs. (0.25) 2.25 18 fl.ozs. (0.563) 14 Current Label Scenario 

8 fl.ozs. (0.25) 2 16 fl.ozs. (0.5) 14 2 applications @ 8 fl.ozs. (0.25 

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. (0187

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. (0.3

Papaya, Mango + 10 fl.ozs. (0.3125) 2.4 24 fl.ozs. (0.75) 14 Current Label Scenario 

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 

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

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 

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

Denotes proposed label mitigation 
Appendix C: Triflumizole Label Table 2, Occupational exposure 

Triflumizole Labeled Crops Current PPE New Proposed PPE Current 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 

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 

Grape Long-sleeved shirt & long pants; 

chemical resistant gloves made of 

any waterproof materials; shoes 

plus socks 

No change to PPE 

12 hours 

Hops Long-sleeved shirt & long pants; 

chemical resistant gloves made of 

any waterproof materials; shoes 

plus socks 

No change to PPE 12 hours