2 

### Prohexadione Calcium 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 Prohexadione Ca Registration Review 11

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Registration Review: Problem Formulation for the Environm ental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposu re Assessment for Prohexadione Calcium

. Anita Ullagaddi, Stephen We nte. November 20, 2012.

2. Prohexadione Calcium: Human-Health Assessment Scoping Document in Support of Registration Review. George F. Kramer, Anwar Y. D unbar, Kelly M. Lowe. November 27, 2012.

3. BEAD Chemical Profile for Registration Review: Prohexadione Calcium. Monisha Kaul, Rafael Prieto, John Faulkner. June 7, 2012.

4. Prohexadione calcium: Review of Human Incidents . Shanna Recore. August 30, 2012.

These and other supporting documents for the pr ohexadione calcium regi stration review case may be found in the docket EPA-HQ-OPP-2012-0870 at http://www.regulations.gov

.3 OVERVIEW

The docket for prohexadione calcium is now open, initiating the first public comment period for this registration review (docket number EP A-HQ-OPP-2012-0870). Prohexa dione calcium is a plant growth regulator that is re gistered for use to control vegeta tive growth in agricultural and non-agricultural use sites. Prohexa dione calcium is registered fo r use on apples, sweet cherries, peanuts, pears, grasses grown for seed, comme rcial and residential lawns, golf courses, recreational fields, cemeteries, and sod farms. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticid e Programs knows about prohexadione calcium, highlighting anticipated data and assessment need s, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing prohexadione calcium’s review.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows ab out prohexadione calcium and what types of new data or other information would be helpful fo r the Agency to receiv e as it moves toward a decision on prohexadione calcium. The Agency encour ages all interested stakeholders to review the PWP and Appendix and to provide comments and additional information that will help the Agency’s decision-making process for this chem ical. In addition to general areas on which persons may wish to comment, there are some ar eas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include: environmental non-profit or interest gro ups; pesticide manufactur ers; agricultural labor or commodity groups; commercial, institutional, resi dential, and other users of pesticides; or the public at large.

The PWP begins by listing the anticipated data needs for prohexadione calcium. Next, it discusses the statutory and regul atory authority for Registration Review. Then the document provides prohexadione calcium chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review timeline. Finally, the Appendix

to this document includes identification and di scussion of some areas that are considered generally in Registration Review along with some additional chem ical case-specific information.4 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data n eeds for prohexadione calc ium. For additional discussion of the anticipat ed data needs, see the Registration Review: Pr oblem Formulation for the Environmental Fate, Ecological Risk, E ndangered Species, and Dr inking Water Exposure Assessment for Prohexadione Calcium and Prohexadione Calcium: Human-Health Assessment Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs for Prohexadione Calcium Registration Review

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

850.1300 Aquatic invertebrate life cycle (freshwater) (daphnid) TGAI 12

850.1400 Fish early life stage toxicity test (freshwater) (bluegill or rainbow trout) TGAI 12

850.2100 Avian oral toxicity (passerine species) TGAI 12 850.4100 Seedling Emergence and Seedling Growth TEP 12
850.4150 Vegetative Vigor TEP 12 875.2100 Dislodgeable foliar residue TEP 12
The studies listed below were previously require d as conditional data requirements for product registrations, and are still outstanding. These studies are listed in this document as background; they

will NOT be included in the anticipated Registration Review DCI because they have already been required by OPP’s Registration Division.

870.7800 Immunotoxicity 1 TGAI Due 12/31/2013 835.6100 Terrestrial Field Dissipation 2 TGAI Due 12/31/2013
TGAI = technical grade active ingredie nt; TEP = typical end-use product;

1 The Immunotoxicity study has been required for new registration actions on prohexadione calcium products.

2 The Terrestrial Field Dissipation study has been required for prohexadione calcium products with turf use sites.5 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 Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website 3

.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration 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 docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of prohexadione calcium.

Table 2 provides a summary of the current regulatory status of prohexadione calcium.

Table 2: PROHEXADIONE CALCIUM CHEMICAL FACTS

PC code 112600

Case Number 7030

CAS Number 127277-53-6 Year first registered 2000 Pesticide Type Plant growth regulator Chemical class None assigned Reregistration Eligibility Decision (RED) Prohexadione calcium was regi stered after November 1984; therefore, is not subj ect to reregistration.

Tolerance Reassessment Decision (TRED) Not applicable

Cumulative group Not applicable 40 CFR Citation Tolerances for prohexadi one are established in 40 CFR 180.547. Dual-use Conventional pe sticidal uses only. Non-pesticidal uses No non-pesticid al uses of prohexadione calcium.

3 http://www.epa.gov/oppsrrd1/registration_review/6 Pesticide Re-evaluation Division, Chemical Review Manager Katie Weyrauch, weyrauch.katie@epa.gov , (703) 308-0166

Registration Division, Product Manager Tony Kish, kish.tony@epa.gov , (703) 308-9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage info rmation for prohexadione. Please see the BEAD Chemical Profile for Registrati on Review: Prohexadione Calcium in the registration review

docket for more details.

Table 3: USE AND USAGE INFORMATION Summary of Use Plant growth regulator that reduces ve getative growth by inhibiting the biosynthesis of gi bberellins, resulting in a decrease in cell elongation and a slowing of cell growth. Use of prohexadione calcium on tree crops, decreases the amount of required pruning. It also decreases vegetative grow th, which can aid mechanical harvesting in grasses grown for seed and peanuts. Use Sites Agricultural: apples, sweet ch erries, peanuts, pears, and grasses grown for seed. Non-agricultural: Sod farms, commercial and residential ornamentals and lawns, recreati onal fields and golf courses. Summary of Usage Between 2006 and 2010, an average of 13,000 pounds active ingredient was applied on an av erage of 51,000 acres of land. The average application rate was 0.25 pounds active ingredient per acre. Usage was only reported on apples . No usage was reported on peanuts, pears, grasses grown for seed, lawns, or turf. Washington state and Michigan reported the highest usage of prohexadione

calcium. Formulation Type Dry flowable Application Methods Aerial a nd ground spray, including airb last, pressurized handwands, back pack, hose-end sprayer and sprinkler can. Technical Registrant BASF Corporation No. of Registrations 4 Section 3 product registrations; 1 technical and 3 end-use products 4

. Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 Confirmation of the following label information: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of

4 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).7 application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

 Use distribution ( e.g. , acreage and geographical distri bution of relevant use sites)

 Median and 90 th percentile reported use rates (lbs a i/A) from usage data – national, state, and county

 Application timing (date of firs t application and application in tervals) – national, state, and county

 Usage/use information for non-agricultural use sites

 Typical application interval (days)

 State or local use restrictions

 Foreign technical registrants not listed above who supply te chnical prohexadione calcium

to the US market

RECENT ACTIONS

A new use on sweet cherries was regi stered on November 18, 2011 (FRL 9326-4).

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for prohexadione calcium was completed on October 13, 2011 for a registration related new use request. The most recent ecological and environmental fate risk assessm ent was completed April 11, 2011 for the same purpose. Findings and conclusions from these risk assessments are summarized in the Registration Review: Problem Formulation for the Environm ental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposu re Assessment for Prohexadione Calcium and Prohexadione Calcium: Human-Health Assessment Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of prohexadione calcium. For human health, EP A anticipates the need to conduct revised residential, and occupational risk assessments during registration review s. If toxicological endpoints or points of departure ar e revised based on the data that are anticipated to be required for registration review, they will be considered in the new assessments, as well as any changes to the standard operating procedures or default exposure assumptions.

Table 4 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.8 Table 4: Anticipated Risk Assess ments for Prohexadione Calcium’s Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms), including endangered species Y -

Incidents N For a discussion of prohexadione calcium’s reported ecological incidents, see page 11 of the Problem

Formulation.

Human Health Dietary

Food N Previous risk assessments indicate low risks of concern for chronic dietary exposure for the general U.S. population and all population subgroups. Therefore, a new dietary assessment is not anticipated for prohexadione calcium duri ng registration review. The dietary assessment may needed to be updated in the future if toxicologi cal endpoints change, new consumption data is used or if a new version of DEEM is used. However, it is not anticipated that the changes will affect risk conclusions. Drinking water N Tier 2 surface wa ter concentration estimates were provided in the most recent EFED assessment. The

estimated surface water concentrations were based on applications to turf at th e highest registered/proposed use rate. Therefore, it is not anticipated that changes in future drinking water assessments will affect risk. However, if the estimated drinking water concentration numbers are updated, then a new drinking water assessment may be conducted. Occupational Handlers (mixers, loaders, applicators) Y Updated occupational handl er exposure assessments may be required based upon revisions to the Agency’s revised scenario-specific surrogate handler exposure

data. Post-application Y An occupational post-application assessment may be conducted based upon an anticipated new requirement for dislodgeable foliar resi due study. Additionally, a new assessment may be conducted if toxicological endpoints change, or other new data received by the Agency impacts exposure assessments.9 Residential

Handlers Y A residential handler assessment may be conducted based on revisions to the Residential SOPs, toxicological endpoint cha nges, or other new data received by the Agency that impact exposure

estimates. Post-application Y A residential pos t-application asse ssment may be conducted based on the revised Residential SOPs, toxicological endpoint cha nges, or other new data received by the Agency that impact exposure

estimates.

Other Aggregate Y Evaluates the combined risk from dietary and residential exposures. Refinements to the residential exposure estimates are anticip ated as a result of the

revised 2012 Residential SOPs. These refinement of exposure estimates are antic ipated to impact the
aggregate assessment.
Cumulative N EPA has not made a common mechanism of toxicity finding for prohexadione calcium and any other substances; and prohexadione calcium does not appear to produce a toxic metabolite produced by other substances. Therefore, no cumulative assessment is planned for prohexadione calcium. Tolerances Y EPA may examine and harmonize prohexadione

calcium’s U.S. tolerances and Canadian maximum residue levels (MRLs) du ring registration review.

Incidents N Because no incident cases for prohexadione calcium were reported in either the Main or Aggregate Incident Data System (IDS), there does not appear to

be a concern that would warra nt further investigation. The Agency will continue to monitor the incident

information and if a con cern is raised, additional analysis will be included in a risk assessment. For a more information, see page 1 of Prohexadione calcium: Review of Human Incidents

.

Guidance for Commenters: Additional ecological information requested for this registration review, and of particular interest to EPA, is described below.

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).

TIMELINE

EPA has created the following estimated timelin e for the completion of prohexadione calcium’s registration review in Table 5 below.10 Table 5: Registration Review for Prohexadio ne Calcium – Projected Registration Review
Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2012 – December Close Public Comment 2013 – February Case Development Final Work Plan 2013 – May

Issue DCI 2014 – Jan – March

Data Submission 2015 – Jan – March Open 30-day Public Comment Period for Dr aft Risk Assessments 2016 – July – Sept Registration Review Decision 60-day Public Comment Period fo r Proposed Registration Review

Decision 2017 – Jan – March

Registration Review Decision and Begin Post-Decision Follow-up 2017 Total (years) 5

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 i ssue a Final Work Plan for the registration review of prohexadione calcium.11 

### Appendix – Additional Areas Consid ered in Prohexadione Calcium’s Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, 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 of MRLs or disparities between U.S. tolerances and MRLs in key export markets, provi ding as much specificity as possible regarding

the nature of the concern.

Water Quality:

Prohexadione calcium is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 5 . In addition, no Total Maximum Daily Loads (TMDL) have been deve loped for prohexadione calcium 6 . More information on impaired

water bodies and TMDLs can be found at the Agency’s website 7

. 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 of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in O PP’s Registration Review Risk Assessment and Management Process 8 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposur e to prohexadione calcium 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.

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

7 http://www.epa.gov/owow/tmdl/

8 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for prohexadione calcium. The ecological risk assessment pla nned during registration review will allow the Agency to determine wh ether prohexadione calcium’s use has “no effect” or “may affect” federally listed threatened or endangered species (lis ted 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 Fisher ies Service (the Services), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent registration decision for prohexadione calcium,

EPA reviewed these data and selected the most sensitive endpoints for re levant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), prohexadione calcium is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 pest icide active ingredients and 9 inert ingredients. Prohexadione calcium is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of regi stration review, EPA will issue future EDSP orders/data call-ins, requiring the su bmission of EDSP screening assays for prohexadione

calcium. For further information on the status of th e EDSP, the policies a nd procedures, the list13 of 67 chemicals, future lists, th e test guidelines and th e Tier 1 screening ba ttery, please visit our

website 9

.

HUMAN STUDIES:

Occupational and Residential

Past prohexadione calcium 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, invo lving 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 e ither fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the tim e the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Huma n Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to cont inued reliance on these studies.

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