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Numbe r EPA-HQ-OPP-2006-011 5 www.regulations.go v



## Triflumizol e

Propose d Interi m Registratio n Revie w Decisio n

Cas e Numbe r 700

3

Septembe r 201 4

Approve d by : 

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Richar d P

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Pesticid e Re-evaluatio n Divisio n

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### 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 Conclu sions for Non-Listed Species .......................... 10

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

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

IV. Proposed Interim Registrati on Review Decision ............................................................... 13

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

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

B. Implementation of Mitig ation 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 .............................................. 173 

### I. Introduction

This document is the Environmental Prot ection 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, F ungicide, and Rodenticide Act (FIF RA). The Agency may issue, when it determines it to be appropriate, an Interim Registration Review Decision before completing a registration review. Among other th ings, the Interim Regist ration Review Decision may: 1) require new risk mitigation measures; 2) impose interim risk mitigation measures; 3) identify data or information required to comp lete 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

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FIFRA, as amended by the Food Quality Pr otection Act (FQPA) of 1996, mandated the continuous review of existing pest icides. All pesticides distributed or sold in the United States generally must be registered by the EPA based on sc ientific 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 intende d to make sure that, as the ability to assess and reduce risk evolves and as polic ies and practices change, all regi stered pesticides continue to meet the statutory standard of no unreasonable a dverse effects. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pes ticides 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/

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In 2006, the Agency implemented the regist ration 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 FIFR A 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. Re gistered application methods for triflumizole include broadcast, foliar spray, root dip, soil drench, chemigation, and seed piece treatment. A Reregistration Eligibility Deci sion document (RED) for triflumizole was not completed because it wa s registered after 1984.

Pursuant to 40 CFR section 155.50, EPA forma lly initiated registration review for triflumizole (case 7003). The following highlight s significant events that have occurred during the registration review of triflumizole:

 March 28, 2007 – Publica tion of triflumizole Summary Document for a 60-day public comment period. The Summary Document incl uded the Preliminary Work Plan (PWP) and was accompanied by the scoping document and problem formulation.4  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 Determ ination 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 Bene fits of Triflumizole and Other Demethylation Inhibiting Fungicides Used on Cherry, Apple, Ha zelnut, Grape, Strawberry and Cucurbits ). This

assessment was conducted to better examine the char acteristics and uses of triflumizole and to qualitatively assess its benef its and overall use patterns. As described in that document,

t riflumizole is a Group 3 DMI fungicide, sometimes referred to as sterol biosynthesis inhibitor (SBI). Triflumizole is register ed for use on a variety of agri cultural crops, including cherry, hazelnut, apple, grape, strawberry, cucurbit, haze lnut, leafy greens, hops, and papaya. It is also registered for use on a number of non-food crops in cluding ornamentals in greenhouses/shade houses, interior scapes, and Christmas trees/coni fers on nurseries and pl antations. 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 (20 04-2011) show triflumizole is primarily used, in terms of pounds and/or acres treated, on cherry, hazelnut, a pple, 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 i ngredient (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 triflumi zole can be found in the triflumizole registration review docke t (EPA-HQ-OPP-2006-0115) at www.regulations.gov

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DMI fungicides, including triflumizole, are classified by the Fungicide Resistance Action Committee as Group 3 fungicides. Group 3 fungicides in general are reported ly one of the most important group of fungicides because of thei r 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 al l of the Group 3 fungicides. Triflumizole is used in disease management programs that altern ate triflumizole with ap plications of other nonDMI fungicides in support of standard stewardshi p 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, triflu mizole was found to be used at a relatively higher percent crop treated. The higher cost and highe r percent crop treated suggests be nefits specific to the use of triflumizole. DMI fungicides in general have be en shown to provide pa rticular value in the control of major diseases such as powdery m ildew 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.6 

### III. Scientific Assessments

A. Human Health

A summary of the Agency’s human health ri sk assessment is presented below. The Agency used the HED scoping document, its supporting documents, and the most updated Agency science policies and risk assessment me thodologies 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 a nd drinking water), resi dential (handler and post-application), aggregate, and occupational (handler and post-app lication) exposure assessments. Risk estimates were below the Agency's level of concern (L OC) 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/

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1. Risk Conclusions

Risk estimates for triflumizole were above the Agency's level of concern (LOC) for the following two occupational scenarios using curr ently required persona l protective equipment (PPE): long-sleeved shirt, l ong 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 harv esting 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 risk s of concern the technical re gistrant, Chemtura Corp., has agreed to amend its registrations and labels to in corporate 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 (revise d MOEs = 400). To address post-application worker risks for mechanically harvesting hops, th e REI should be 3 days (revised MOEs = 330). However, to address identified eco logical risks of concern for hops, the registrant has agreed to increase the Post-Harvest Interval (PHI) to 7 da ys. Because the PHI of 7 days (for hops) is greater than a 3-day REI, the PH I will provide sufficient protec tion for re-entry by occupational workers and therefore a 3-day RE I for hops is not required.7 2. Tolerances

Tolerances are currently established for resi dues 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

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The following tolerance amendments are ne eded for triflumizole: (1) the residue definition for the tolerance expression for triflumi zole should be modified in accordance with the current policy on tolerance definitions (descr ibed on pg. 3-4 of the Human Health Risk Assessment); and (2) the tolerance levels for cert ain commodities (listed below) should reflect recommendations made in a previous review but are not currently re flected 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 “co riander, leaves.” Also, the following tolerances will be deleted from 180.476(a)(2): cattle, m eat; egg; goat, meat; hog, fat; hog, meat; hog, meat byproducts; horse, meat; milk; poultry, fat; poultr y, meat; poultry, meat byproducts; and sheep, meat. Tolerance levels for the following commod ities will be lowered from 0.5 to 0.10 ppm: fat of cattle, sheep, goat, and horse. Tolerance le vels for the following commodities should be lowered from 0.5 to 0.20 ppm: meat byproduc ts of cattle, sheep, goat, and horse.

3. Human Incidents

A small number of minor human health inci dents 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 Inci dent Database System. These incidents were

classified as moderate severi ty. A query of SENSOR-Pesticides 2006-2010 identifies a total of 23 cases (2 moderate severity and 21 low se verity). 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 sugges t 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 Hu man 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 a nd 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 Determ ination of Triflumizole and Refinements to the Triflumizole Preliminary Risk Assessment in Support of Registration Review dated May 8, 2014 available in8 the public docket EPA-HQ-OPP-20 06-0115, which can be accessed at http://www.regulations.gov/

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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, fr eshwater fish and estuarine/marine invertebrates. The Agency is currently working with its fe deral counterparts and other stake holders to implement an interim approach for assessing potential risk to listed spec ies and their designated cr itical habitats. Once the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats are finalized, th e Agency will complete its endangered species assessment for triflumizole. As such, only scre ening-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 so ils with low organic matt er). Triflumizole’s moderate adsorption characteristi cs suggests that triflumizole has a low potential to reach groundwater. Triflumizole will r each surface water in both the di ssolved form and sorbed onto soils and organic material for se veral weeks following application.

The major pathways of triflumizole degrad ation are hydrolysis unde r acidic and alkaline conditions, anaerobic aquatic metabolism, and to a lesser extent aerobic soil metabolism. Halflives varied depending on environment c onditions 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 quo tients (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 ev aluates the potential for a risk of concern to that category. Risk characterization provides further inform ation 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 ris k, and the nature of the effects observed.

6. Overview of Ecological Risk Conclusions

Conservative assumptions were made in the eco logical 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 triflu mizole. For all other non-listed taxa, RQs were below target LOCs for all uses and there are no risks of concern.9 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. Howeve r, 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 reprodu ction 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 a ssessment ranged from 0.1 (leafy greens) to 74.42 (ornamentals).

Chronic Mammalian Risk Char acterization & Mitigation

Conservative assumptions in the screening le vel risk assessment include the use of (1) maximum labeled rates; (2) upper bound Kenaga values (95 th percentile) to estimate environmental concentrations (EECs) for ma mmals; and (3) 100% of a mammalian diet is assumed to come from one food type (on a treated field). To better characte rize chronic risks to non-listed mammals, the following refinements were made to the risk assessment:

(1) Incorporated average Kenaga EECs (50 th 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 maximu m labeled rates as a conservative screen. Alternative application scenarios were a ssessed using estimated average maximum application rates, average num ber of applications, and aver age application intervals.

Based on available use and extension inform ation, 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 typi cal rates are used, the RQs are decreased significantly. For cherries RQs decreased from 58.54 to 20.54. For a pples/pears the RQs

decreased from 41.16 to 14.58.

For more information regarding the revi sions and additional characterization of

mammalian risk see the Refinements to the Triflumizole Pr eliminary Risk Assessment in Support of Registration Review

.10 Birds, Terrestrial Plants, Terrestrial Invertebrates

There are no acute or chronic risks of con cern 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 or ganisms is potential runoff and spray drift from labeled applications of triflumizole. Acut e and chronic risk estimat es were below the LOC

for non-listed freshwater and estuarine/marine fi sh (surrogates for aquatic-phase amphibians), freshwater and estuarine/marine invertebrates, an d aquatic vascular and n on-vascular plants for all uses of triflumizole. Therefore, no risk s of concern are anticipat ed for non-listed aquatic organisms based on the registered uses of triflumizole.

9. Ecological Incidents

A review of the ecological incident inform ation system (EIIS) and the avian monitoring information system (AIMS), which is mainta ined 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 Conc lusions 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 sc reening level risk assessment range from 0.1 to 74.42). To mitigate the identified risks, Chemtu ra (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. Thes e 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. Am ended 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 expect ed 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 ch anges (mitigation) to the various maximum applications rates, RTIs, and to tal number of annual applications represent significant reductions to the chronic mammalian risk picture; and (3 ) in addition, the Agency conducted a qualitative11 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 contro lling 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 obligati ons under both the Endangered Species Act (ESA) and FIFRA. While the risk assessment supporti ng this Proposed Interim Registration Review Decision evaluates risks to species that are not subj ect to the ESA, EPA is still in the process of conducting a risk assessment for endangered and th reatened (listed) species and their designated

critical habitats for triflumizole. In this Proposed Interim Regist ration Review Decision, therefore, EPA has not completed effects determin ations 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 Servi ces), and the U.S. Department of Agriculture (USDA) released a summary of th eir 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 Appro aches), 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 th at EPA and the Services must conduct in connection with their obligations under the Endangered Sp ecies Act (ESA) and FIFRA.

The joint Interim Approaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, the EPA presen ted the joint Interim Approaches at the December 2013 Pesticide Program Dialogue Co mmittee (PPDC) and State-FIFRA Issues Research and Evaluation Group ( SFIREG) meetings, and held a stakeholder workshop in April 2014, allowing additional opportunities for stakeholde rs to comment on the Interim Approaches. As part of a phased, iterative process for deve loping the Interim Approaches, the agencies will also consider public comments on the Interim Appr oaches 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 de velop and work toward implementation of the Interim Approaches to assess the potential risk s 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 crit ical 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 th at listed species and designated12 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 fo r this particular registration review case. Once the agencies have fully developed and implemente d 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 subseq uent analyses for triflumizole as part of completing this registration review.

D. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA review s numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute,

subchronic and chronic toxici ty, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or syst emic toxicity. These studies include endpoints which may be susceptible to endocrine influenc e, including effects on endocrine target organ histopathology, organ weights, es trus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard asse ssments, EPA evaluates

acute tests and chronic studies that assess growth, developmen tal and reproductive effects in different taxonomic groups. As part of its most recent registration decision for triflumizole, EPA

reviewed these data and select ed 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 th e Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredie nts) may have an effect in hu mans or wildlife similar to an effect produced by a “naturally occurring estr ogen, 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 intera ct with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go thro ugh Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to th e next stage of the EDSP where EPA will determine which, if any, of the Ti er 2 tests are necessary based on the available data. Tier 2 testing is designe d to identify any adverse endocr ine-related effects caused by the substance, and establish a dose-re sponse relationship between the dos e 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 pest icide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening, which included triflumizole, was published on June 14,

2013 1 and includes some pesticides scheduled fo r 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 batt ery, please visit our

website. 2

In this Proposed Interim Registration Revi ew Decision, EPA is making no human health or environmental safety findings associated with the EDSP screening of triflumizole. Before completing this Registration Review, the Agen cy 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 Decisi on. Except for the EDSP and Endangered Species Act (ESA) components of the triflumizole regist ration review case, the Agency has made the following proposed interim decision: (1) changes are required to triflumizole products (reduction of maximum number of applications; reducti on 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, cucu rbits, brassica leafy greens, head & stem brassica, leafy greens (e.g. spinach), filb ert/hazelnut, hops, papaya, mango, pineapple (dip application) a nd ornamentals; and (2) the following changes are required to mitigate risks to occupational handlers and post-a pplication: (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 pr oduct registrant for triflumizole, Chemtura Corporation, who has volunt arily agreed to revise all affected labels accordingly.

In the interim, EPA is making no human h ealth or environmental safety findings associated with the EDSP screening of triflumizole. Before completing this Registration Review, the Agency will make an EDSP FFDCA s ection 408(p) determination. Likewise, before completing this Registration Review, the Agency will conduct an ecological risk assessment to address the Agency’s obligati ons under both the Endangered Sp ecies Act (ESA) and FIFRA. While the risk assessment supporting this Pr oposed 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 th reatened (listed) species and their designated

critical habitats for triflumizole. In this Proposed Interim Regist ration Review Decision, therefore, EPA has not completed effects determin ations for listed species associated with the registered uses of triflumizole. The Agency is issuing a Proposed Inte rim 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). Howe ver, 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 Ag ency for review and approval proposed amended labels. The mitigation measures and required la bel amendments are described in Appendices A

and B below.Docket Number EPA-HQ-OPP-2006-0115www.regulations.gov16Appendix A: Summary of Actions Taken for TriflumizoleRegistration Review Case#: 7003PC Code: 128879Trinexapac-ethyl Type: Systemic broad spectrum fungicideTrinexapac-ethyl Family: Imidazole (group 3) fungicideMode of Action:Ergosterol biosynthesisinhibitor in fungiAffected Population(s)Source of ExposureRoute of ExposureDuration ofExposureRisk of ConcernAction(s) TakenNon-listed mammalsDirectapplicationSpray driftRunoffIngestionChronicDirectSee Appendix COccupational handlersDirectapplication tocropDermalShort-/Intermediate-termDirectIn addition to current labeled PPErequirements, chemical resistanthat during open cab air blastapplications to grapes, apples,pear, and cherries.Occupational postapplication workersResidues onsite oftreatmentDermalShort-termDirectIncrease REI to 3 days formechanically harvesting hops and1 day for girdling grapes (table andraisin).Pre-harvest interval (PHI) of 7days for hops supersedes 3 dayREI.All other labeled uses shouldmaintain REI of 12 hours.17Appendix B: Triflumizole Label Table 1, Proposed Rate and RTI Label MitigationProcure CropsMax. Rate Procure480SC perApplication(lbs.ai./A)Max.no. ofAppls./ Crop/ Yr.Max. Appl. RateProcure 480SCper Acre perYear (lbs.ai./A/yr.)Min.RTI(days)Label Mitigation CommentsPome Fruit Crop Group 11-10(Apple, pear)16 fl.ozs. (0.5) 4 64 fl.ozs. (2.0) 7Current Label Scenario16 fl.ozs. (0.5)456 fl.ozs. (1.75)14/21/14Cherry 16 fl.ozs. (0.5) 6 96 fl.ozs. (3.0) 7Current Label Scenario16 fl.ozs. (0.5)456 fl.ozs. (1.75)14/21/14Curcurbits 8 fl.ozs. (0.25) 5 40 fl.ozs. (1.25) 7Current Label Scenario6-8 fl.ozs. (0.1875-0.25)3-424 fl.ozs. (0.75)73 applications @ 8 fl.ozs. (0.25 lbs. ai.)/A or 4 applications@ 6 fl.ozs. (0.1875 lbs.ai.)/ABrassica Leafy Greens 8 fl.ozs. (0.25) 2.25 18 fl.ozs. (0.563) 14Current Label Scenario8 fl.ozs. (0.25)216 fl.ozs. (0.5)142 applications @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 daysHead & Stem Brassica 8 fl.ozs. (0.25) 2.25 18 fl.ozs. (0.563) 14Current Label Scenario8 fl.ozs. (0.25)216 fl.ozs. (0.5)142 applications @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 daysLeafy Greens (ex. spinach) 8 fl.ozs. (0.25) 2.2518 fl.ozs. (0.563) 14 Current Label Scenario8 fl.ozs. (0.25)216 fl.ozs. (0.5)142 applications @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 daysFilbert / Hazelnut 6 fl ozs. (0.1875) 4 24 fl.ozs. (0.75) 10 Current Label Scenario6 fl ozs. (0.1875)212 fl.ozs. (0.375)102 applications @ 6 fl.ozs. (01875 lbs.ai.)/A @ 10 daysHops 12 fl ozs. (0.375) 3 36 fl. ozs. (1.125) 14 Current Label Scenario12 fl ozs. (0.375)224 fl.ozs. (0.75)142 applications @ 12 fl.ozs. (0.375 lbs.ai.)/A @ 14 daysPapaya, Mango + 10 fl.ozs. (0.3125) 2.4 24 fl.ozs. (0.75) 14 Current Label Scenario8 fl.ozs. (0.25)18 fl.ozs. (0.25)NAOrnamentals (Tguard SC) 64 fl.ozs. (2.0) NS> 96 fl.ozs. (3.0) 7 Current Label Scenario8-16 fl.ozs. (0.5)2-432 fl.ozs. (1.0)142 applications @ 16 fl.ozs. (0.5 lbs.ai.)/A @ 14 days or 4appls. @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 daysOrnamentals (Tguard SC/LS) 32 fl.ozs. (1.0) NS96 fl.ozs. (3.0) 7 Current Label Scenario8-16 fl.ozs. (0.5)2-432 fl.ozs. (1.0)142 applications @ 16 fl.ozs. (0.5 lbs.ai.)/A @ 14 days or 4appls. @ 8 fl.ozs. (0.25 lbs.ai.)/A @ 14 daysDenotes proposed labelmitigation17Appendix C: Triflumizole Label Table 2, Occupational exposureTriflumizole LabeledCropsCurrent PPENew Proposed PPECurrentREINew Proposed REIPome Fruit Crop Group11-10(Apple, pear)Long-sleeved shirt & long pants;chemical resistant gloves made ofany waterproof materials; shoesplus socksIn addition to current PPE require:“chemical resistant hat forapplicators using open cab air blastequipment”12 hoursNo change to REICherry Long-sleeved shirt & long pants;chemical resistant gloves made ofany waterproof materials; shoesplus socksIn addition to current PPE require:“chemical resistant hat forapplicators using open cab air blastequipment”12 hoursNo change to REIGrape Long-sleeved shirt & long pants;chemical resistant gloves made ofany waterproof materials; shoesplus socksNo change to PPE12 hoursMaintain 12 hours forwine grapesw/addition of:“1 day REI forgirdling of table andraisin grapes”Hops Long-sleeved shirt & long pants;chemical resistant gloves made ofany waterproof materials; shoesplus socksNo change to PPE12 hoursPre-harvest interval(PHI) of 7 days forhops supersedes 3 dayREI.