Docket Number EPA-HQ-OPP- 20 15-0381 www.regulations.gov



# Thidiazuron Preliminary Work Plan

Registration Review: Initial Docket Case Number 003

Approved by:

Date: 

# June 2015

**CU-d--Y**

**~** Richard P. Keigwin, Jr
. Director Pesticide Re-evaluation Division

**&,f .;)~** 

**/** 

### a ot5

### Thidiazuron Preliminary Work Plan - Table of Contents

OVERVIEW ................................................................................................................................... 3 ANTICIPATED DATA NEEDS ........................................................................... ......................... 4 STATUTORY AND REGULATORY AUTHORITY
. . . . .. . . . . .. . ................ ..... ............ ............. ... . .... 5 CHEMICAL FACTS ...................................................................................................................... 5
USE AND USAGE INFORMATION ............................................................................................ 6 RECENT ACTIONS ........... ..... ............... ............. ............. ..................... . ...... . ... ... . . ... . . . . .... . .. .... . ...... 7 ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 7 TIMELINE ............................................... . .......................................................... . ....... ........ . ... . ....... 9
NEXT STEPS
...... ... . . . ..... ....... . ................. . . . ................ . . . ....................................... .. .. .... . . ... ... . ... .... 10 Appendix

- Additional Areas Considered in the Thidiazuron Registration Review ................ 11
References: This Preliminary Work Plan summarizes the Environmental Protection Agency's current position based on the following documents: 

### 1. Registration Review : A Joint Problem Formulation and Draft Risk Assessment of the Environmental Fate and Ecological Risk ofThidiazuron. Stephen Carey and William Eckel. June 16,2015. 2. 

### Thidiazuron: Human Health Combined Scoping Document and Draft Risk Assessment for Registration Review. Ronnie Bever, Ideliz Negron-Encarnacion , and Alexandra Gavelek
. June 9, 2015. 3. 

### Thidiazuron : Tier I Review of Human Incidents. Shanna Recore and Elizabeth Evans. February 5, 2015. 4. 

### BEAD Chemical Profile (BCP)for Registration Review: Thidiazuron (10301)
. Sunil Ratnayake, Cynthia Doucoure, and Stephen Smearman. January 26, 2015. 5. 

### Thidiazuron Screening Level Usage Analysis (SLUA). September 22, 2014. 6. 

### EFED Master Label Report. September 29, 2014. 7. 

### HED Master Label Report
. September 29, 2014. 8. 

### Thidiazuron : Drinking Water Exposure Assessment Memorandumfor Preliminary Risk Assessment in Support ofThidiazuron Registration Review. Iwona Maher and William Eckel. May 13,2015. These and other supporting documents for the thidiazuron registration review case may be found in the docket EPA-HQ-OPP-2015-038 1 at http: //www.regulations.gov. 2

### OVERVIEW The docket for thidiazuron is now open, initiating the first public comment period for this registration review (docket number EPA-HQ-OPP-2015-0381). Thidiazuron is a phenylurea herbicide registered for use as a pre-harvest defoliant in cotton. Thidiazuron acts to reduce the foliage and immature fruiting structures which contribute to the staining of harvested cotton and also acts to facilitate cotton harvesting. Thidiazuron is not registered for any non-agricultural uses. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about thidiazuron, highlighting anticipated data and assessment needs , identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing the registration review for thidiazuron. This PWP also includes a summary of the draft human health and ecological risk assessments for thidiazuron registration review. The last comprehensive human health and ecological risk assessments for thidiazuron were completed in 2005 in support of the Reregistration Eligibility Decision (RED). Only minor updates to the RED risk assessments were required to meet current risk assessment standards , so EPA developed a combined scoping document/draft human health risk assessment and a combined problem formulation/draft ecological risk assessment. Both draft risk assessments and this PWP are now in the docket and the 60-day public comment period has commenced

. The registration review process was designed to include a public participation component to so licit input from interested stakeholders. The Agency intends , by sharing this information in the docket, to inform the public of what it knows about thidiazuron and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on thidiazuron. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional information that will help the Agency's decision-making proce ss for this chemical. In addition to general areas on which persons may wish to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include: environmental non-profit or interest groups; pesticide manufacturers ; agricultural labor or commodity groups; commercial, institutional , residential , and other users ofpesticides ; or the public at large. The Preliminary Work Plan begins by listing the anticipated data needs for thidiazuron

. Next, it discusses the statutory and regulatory authority for Registration Review

. Then the document provides chemical facts, use and usage information, recent actions, conclusions ofthe completed human health and ecological risk assessments, and a projected registration review timeline for thidiazuron. Finally, the Appendix to this document includes identification and discussion of some areas that are considered generally in Registration Review along with some additional chemical case-specific information.



### 3ANTICIPATED DATA NEED S Table 1 below summarizes anticipated data needs for thidiazuron. For additional discussion of the anticipated data needs, see the 

### Registration Review : A Joint Problem Formulation and Draft Risk Assessment of the Environmental Fate and Ecological Risk ofThidiazuron and 

### Thidiazuron: Human Health Combined Scoping Document and Draft RiskAssessment for Registration Review.
T able 1: A nticipated Data Need s for th e Thidiazuron Registration Review Estimated Guideline Study Title 1 Timeframe Number 1 Test Material (Months from receipt ofDCI)
835.6100 Terrestrial field dissipation (storage stabi lity TEP 12 portion only) 850.2100 Avian acute oral toxicity (passeri ne species) TGA l 12 850.3040 Field testing for po ll inators (tier lll ) 2 TEP 24 850
.6100 Environmental chemistry method for water and TGA I 12 associated independent laboratory va lidation 850
.6100 Environmental chemistry method for soi l and TGAI 12 associated independent laboratory va l i dation 3 Non- Honeybee larval acute oral toxicity (tier f) TEP 12 guideline

Non- Honeybee adult I0-day chronic oral toxicity (tier TEP 12 guideline I)

Non- Honeybee larval chronic oral toxicity (tier 1 )4 TEP 12 guideline

Non- Residues in po ll en and nectar /fie l d r esidue TEP 24 guideline analysis (tier I11 )2

Non- Semi-field toxicity testing for po ll inators (tier ll)2 TEP 24 guideline

Non- Radio-validatio n for to l erance enforcement TEP 12 guideline method TU-002-A06-0I (livestock commodities) TGAI = techmcal grade active mgredient ; TEP =typical end-use product ;

1 On June 27,2012, EPA announced certain revisions in harmonized guideline series 850

- Ecological Effects Tests

- including renumbering and other designations or changes for some guideline studies. See "Final Test Guidelines; OCSPP 850 Series ; Notice of Availability" 77 FR 38282, June 27 ,2012. http ://www .regu lation s.gov/# ! documentDetail; D =EPA-HQ-OPPT-2009-0 154-0028 2 Tier II and tier Ill pollinator studies are required based on results of tier I pollinator studies. 3 An environmental chemistry method for soil has been submitted to EPA, but has not yet been reviewed. EPA will

complete this review during registration review
. 4 It is possible to conduct the larval chronic oral toxicity study in such a way as to derive both an LD 50 (acute

endpoint) and a NOAEC (chronic endpoint). If both an LD 5o and NOAEC can be derived from a single study, then a separate acute larval toxicity study is not needed. 4

### STATUTORY AND REGULATORY AUTHORITY The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling

. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change , all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. 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 change occurs , products in the marketplace can be used safely. Information on this program is provided on EPA ' s website

. 5 The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide , Fungicide, and Rodenticide Act (FIFRA), and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency ' s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision

. After reviewing and responding to comments and data received in the docket during this initial comment period , the Agency will develop a combined Final Work Plan (FWP) and Proposed Interim Registration Review Decision

. 

### CHEMICAL FACTS Table 2 provides a summary of the chemical facts for thidiazuron

. Table 2: Chemical Facts for Thidiazuron PC code 120301 Case Number 003 CAS Number 51707-55

-2 Year first registered 1982 Pesticide Type Plant growth regulator Chemical class Phenylurea Reregistration Eligibility A RED for thidiazuron was completed in September 2005. Decision (RED) Tolerance Reassessment Not app li cable , tolerance reassessment was included in the RED
. Eligibility Decision (TRED)

5 http ://ww w.epa .gov/opp srrd !/registration

_revi ew/ 

### 5

### Table 2: Chemical Facts for Thidiazuron Cumulative group Not applicable. Thidiazuron has not been identified as a member of a cumulative group that shares a common mechanism of toxicity. 40 CFR Citation Tolerances for thidiazuron are established in 40 CFR § 180.403. Dual-use Thidiazuron is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses . Non-pesticidal uses There are no identified non-pesticidal uses of thidiazuron. Pesticide Re-evaluation Khue Nguyen, nguyen.khue @ epa.gov, 703-347-0248 Division , Chemical Review Manager Registration Division, Kathryn Montague , montague.kathryn @epa.gov , 703-305-1243 Product Manager 

### USE AND USAGE INFORMATION Table 3 summarizes the use and usage information for thidiazuron. Please see the BEA D Chemical Profile (BCP)for Registration Review : Thidiazuron (1 0301 ) in the registration review docket for more details. 

### Table 3: Thidiazuron Use and Usage Information Summary of Use Thidiazuron is a phenylurea plant growth regulator registered for use as a cotton defoliant. 

### It is applied as a pre-harvest treatment to reduce the fo liage and immature fruiting structures which contribute to the staining ofharvested cotton
. Use Sites Thidiazuron is only applied to cotton. There are no registered non-agricultural uses. Summary of Usage From 2008-20 12, an average of approximately 250 ,000 lbs of thidiazuron were app lied annually to 3.8 million acres of cotton. The top states with the highest percentage of lbs thidiazuron applied were Georgia, Texas , Mississippi , and Arkansas. Georgia and Texas are the states with the highest use and together they account for nearly half of the cotton acreage treated with thidiazuron. Formulation Type(s) Wettablepowder, suspension or emulsifiable concentrate Application Method(s) Ground or aerial appli cation equipment Technical Registrant(s) Bayer Cropscience LP; Loveland Products , Inc .; Nufarm Limited ; Arysta Lifescience North America, LLC ; and Adama Celsius Property B.V., Amsterdam (NL) No. of Registrations 24 Section 3 products 6 Restricted Use No

6 Section 3 product label s can be obtained from the Pesticide Product L a

bel Sys t em (PPLS) website (http :/I oaspub.epa
.gov/pestlab 1/ppIs
. home). 6Guid ance for Comm enters: Additional areas of 

### use and usage related information requested for this registration review, and ofparticular interest to EPA, are described below.

• Confirmation of the following label information: sites of application; formulations ; application methods and equipment; maximum application rates; frequency of application, application intervals , and maximum number of applications per season; and geographic limitations on use. • Use distribution (e.g., acreage and geographical distribution of relevant use sites). • Median and 90 111 percentile reported use rates (lbs ai/A) from usage data

- national , state, and county. • Typical application timing (date of first application and application intervals)

- national , state, and county. • Typical application interval (days). • State or local use restrictions. • Foreign technical registrants not listed above who supply technical thidiazuron to the US market. 

### RE CENT AC TIONS There are no recent actions for thidiazuron. 

### ANTICIPATED RI SK ASSESSMENTS FOR REGISTRATION REVIEW The most recent comprehensive human health risk assessment for thidiazuron was completed in 2005 in preparation for the RED. The most recent ecological and environmental fate risk assessment was completed in 2005 for the same purpose. Findings and conclusions from these risk assessments are summarized in the 

### Registration Review: A Joint Problem Formulation and Draft Risk Assessment of the Environmental Fate and Ecological Risk ofThidiazuron and 

### Thidiazuron: Human Health Combined Scoping Document and Draft Risk Assessment for Registration Review. During registration review, the Agency anticipates the need to reassess risk for pollinators and complete an endangered species risk assessment for all uses ofthidiazuron. For human health , EPA anticipates the need to assess endocrine disruption risks for thidiazuron during registration review. If toxicological endpoints or points of departure are revised based on the data that are anticipated to be required for registration review , they wi ll be considered in the revised assessments, as well as any changes to the standard operating procedures or default exposure assumptions. Table 4 below summarizes the recently comp leted registration review human health and ecological risk assessments as detai led in the 

### Registration Review: A Joint Problem Formulation and Draft RiskAssessment of the Environmental Fate and Ecological Risk ofThidiazuron and the 

### Thidiazuron: Human Health Combined Scoping Document and Draft RiskAssessment for Registration Review.

7Table 4: Summary of Preliminary Human Health and Ecological Risk Assessments for the Thidiazuron Registration Review Type of Risk Assessment Conducted? Notes Ecological and Environmental Fate Comprehensive ecological 

### y The registration review risk assessment identified risk assessment potential drinking water risk to birds, terrestrial-phase amphibians, and reptiles foraging in treated fields , and risk to terrestrial plants. An endangered species assessment was not completed. The Agency anticipates a more in-depth evaluation in the future to determine the potential co-occurrence of listed species and the areas in which cotton is grown . Incidents Will check for There were 4 reported ecological incidents for updates thidiazuron
. For a discussion of reported ecological incidents , see page 17 of the Problem Formulation
. Human Health Dietary Food 

### y The registration review human health risk assessment Drinking water 

### y did not identify any dietary risks of concern . The highest exposed population subgroup was children 1- 2 years old at 9.3 % ofthe cPAD. Occupational Handlers (mixers , loaders , 

### y The occupational handler assessment did not identify applicators) any risks of concern. MOEs ranged from 30 ,000 to 1 ,500 ,000. Post-application 

### y A qualitative occupational post-application risk assessment was completed since onl y dermal exposure was expected and no dermal hazard was identified for thidiazuron. No post-application risks were identified. Residenti al Handlers N A residential handler assessment was not completed because thidiazuron is not registered for residential use. Post-application 

### y Although thidiazuron is not registered for residential use, potential residential exposure could occur via spray drift
. A residential post-application spray drift assessment was completed and did not identif y any risks of concern. Other Aggregate 

### y Evaluates the combined risk from dietary and residential exposures. The Agency only considered exposure from food and drinking water because thidiazuron is not registered for residential use . No aggregate risks were identified.



### 8Cumulative N Thidiazuron is not currently a member of a cumulative group , therefore, no cumulative risk assessment was completed. Tolerances 

### y The Agency is proposing to modify the tolerance expression for thidiazuron to be in line with current policy

. The Agency is also proposing to modif y tolerances for various cotton commodities based on recent residue data

. Incidents Will check for Only 1 human incident of minor severity was reported updates for thidiazuron

. For a discussion ofreported human incidents for thidiazuron , see page 27 of the 

### Thidiazuron : Human Health Combined Scoping Document and Draft RiskAssessment for Registration Review and the 

### Thidiazuron: Tier I Review of Human Incidents.

TIMELINE EPA has created the following estimated timeline for the completion of the thidiazuron registration review in Table 5 below. Table 5: Projected Thidiazuron Registration Review Timeline Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period for June 20 15--completed Preliminary Work Plan and Draft Risk Assessments 7 Close Public Comment August 2015 Case Development Final Work Plan Not applicable Registration Review Decision 60-day Public Comment Period for Proposed March 2016--May 2016 Registration Review Decision Registration Review Decision and Begin Post-Decision September 2016 Follow-up Issue DCI During post-interim decision followup Data Submission During post-interim decision followup Total (months) 15 months

7 Th e regul ation s go verning Re gistration Review gen erall y require the Agenc y to provide a public comment period of at least 30 calend ar days for draft ri sk as sessments; see 40 CFR Part 155.53 (c). For conventional pesticide s, the Age nc y pl ans to provide a 60 calendar day public comment period generall y for draft risk asses sments. 

### 9

### NEXT STEPS After the 60-day public comment period closes, the Agency will review and respond to any comments received in a timely manner and then issue a Proposed Interim Registration Review Decision for the registration review ofthidiazuron. Subsequently , the Agency will hold a 60-day public comment period on the Proposed Interim Registration Review Decision , review and respond to comments , and issue the Interim Registration Review Decision for thidiazuron . EPA is undertaking a streamlined risk assessment process for the registration review of thidiazuron because of a number of factors: i) thidiazuron is only used on one crop in a geographically limited area of the United States , ii) the use pattern for thidiazuron has not changed since implementation of RED label changes, iii) the human health , ecotoxicology, and environmental fate databases for thidiazuron are mostly complete, iv) the existing honeybee data did not indicate immediate risks to pollinators , and v) only minor updates to the RED risk assessments were required to meet current risk assessment standards
. Because of these reasons , the Agency did not see the need to issue a DCI for thidiazuron prior to risk assessment. The Agency anticipates issuing a DCI during post-Interim Registration Review Decision follow-up
.

10

### Appendix- Additional Areas Considered in the Thidiazuron Registration Review PUBLIC COMMENTS AND FEEDBACK: Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments , data submissions, or reference to sources of additional information could be of particular use . 

### Trade Irritants : Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack ofMRLs or disparities between U.S. tolerances and MRLs in key export markets , providing as much specificity as possible regarding the nature of the concern. 

### Water Quality: Thidiazuron is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 8 In addition, no Total Maximum Daily Loads (TMDL) have been developed for thidiazuron. 9 More information on impaired water bodies and TMDLs can be found at the Agency's website. 10 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A ofthe 

### OPP Standard Operating Procedure : Inclusion of Impaired Water Body and Other Water Quality Data in OPP ' s Registration Review RiskAssessment and Management Process'' in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments. 

### Environmental Justice: EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race , color, national origin, or income, in the development, implementation, and enforcement of environmental laws , regulations, and policies. To help address potential environmental justice issues , the Agency seeks information on any groups or segments of the population who , as a result of their location , cultural practices , or other factors, may have atypical, unusually high exposure to thidiazuron compared to the general population. Please comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to the general population.

8 http ://iasp ub.epa .gov/tmdl waters I0/attai ns nation cy.cause detail 303d?p cause group id= 885 9http ://iaspub.epa.gov/tmdl waters I0/attains nation

.tmdl pollutant detail ?p pollutant group id = 885&p pollutant

group name= PEST IC ID ES 10 http ://www.epa . gov/owow/tmdl/ 1 1 http ://www.epa.gov/oppsrrd I/registration review/water quality sop.htm 

### 11

### ENDANGERED SPEC IES: A risk assessment that supports a complete endangered species determination has not been conducted for thidiazuron. The endangered species risk assessment planned during registration review will allow the Agency to determine whether use of thidiazuron has " no effect" or " may affect" federally listed threatened or endangered species (listed species) or their designated critical habitats
. When an assessment concludes that a pesticide ' s use " may affect" a listed species or its designated critical habitat, the Agency will consult with the U
.S
. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.



### ENDO CRINE 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 reregistration decision for thidiazuron, 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), thidiazuron is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP)
. EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a "naturally occurring estrogen , or other such endocrine effects as the Administrator may designate. " The EDSP employs a two-tiered approach to making the statutorily required determinations
. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen , androgen , or thyroid (E , A , or T) hormonal systems
. Chemicals that go through Tier 1 screening and are found to have the potential to interact withE , A, or T hormonal systems will proceed to the next stage ofthe 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 theE, A , or T effect. Under FFDCA section 408(p) , the Agency must screen all pesticide chemicals
. Between October 2009 and February 2010 , EPA issued test orders/data call-ins for the first group of 67 chemicals , which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14 , 2013 12 and includes some

12 See http: //www .r egul ation s.gov/# !documentD etail ;D=EPA- HQ-OPPT

-2009- 0477

-0074 for the fin al second li st of chemicals
. 12pesticides scheduled for registration review and chemicals found in water
. Neither of these lists should be construed as a list of known or likely endocrine disruptors. 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. 13


### HUMAN STUDIES: 

### Occupational and Residential Past thidiazuron risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was conducted. All applicab le requirements of EPA's Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

13 http ://www .epa .gov/endo/ 13