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 Environmental Protection Agency's current position 

based on the following documents: 

1. Registration Review: Problem Formulation for the Environmental Fate, Ecological Risk, 

Endangered Species, and Drinking Water Exposure Assessment for Prohexadione Calcium. 

Anita Ullagaddi, Stephen Wente. November 20, 2012. 

2. Prohexadione Calcium: Human-Health Assessment Scoping Document in Support of 

Registration Review. George F. Kramer, Anwar Y. Dunbar, 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 prohexadione calcium registration 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 EPA-HQ-OPP-2012-0870). Prohexadione calcium is a 

plant growth regulator that is registered for use to control vegetative growth in agricultural and 

non-agricultural use sites. Prohexadione calcium is registered for use on apples, sweet cherries, 

peanuts, pears, grasses grown for seed, commercial and residential lawns, golf courses, 

recreational fields, cemeteries, and sod farms. This Preliminary Work Plan (PWP) document 

explains what EPA's Office of Pesticide Programs knows about prohexadione calcium, 

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 prohexadione calcium’s review. 

 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about prohexadione calcium and what types of new 

data or other information would be helpful for the Agency to receive as it moves toward a 

decision on prohexadione calcium. 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 process 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 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 regulatory 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 discussion of some areas that are considered 

generally in Registration Review along with some additional chemical case-specific information. 

 
4

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for prohexadione calcium. For additional 

discussion of the anticipated data needs, see the Registration Review: Problem Formulation for 

the Environmental Fate, Ecological Risk, Endangered Species, and Drinking 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 required 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 Immunotoxicity1 TGAI Due 12/31/2013 

835.6100 Terrestrial Field Dissipation2 TGAI Due 12/31/2013 

TGAI = technical grade active ingredient; 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 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 website3

. 

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 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 registered after November 1984; 

therefore, is not subject to reregistration. 

Tolerance Reassessment 

Decision (TRED) 

Not applicable 

Cumulative group Not applicable 

40 CFR Citation Tolerances for prohexadione are established in 40 CFR 180.547. 

Dual-use Conventional pesticidal uses only. 

Non-pesticidal uses No non-pesticidal 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 information for prohexadione. Please see the BEAD 

Chemical Profile for Registration 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 vegetative growth by inhibiting 

the biosynthesis of gibberellins, 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 growth, which can aid mechanical 

harvesting in grasses grown for seed and peanuts. 

Use Sites Agricultural: apples, sweet cherries, peanuts, pears, and grasses 

grown for seed. 

Non-agricultural: Sod farms, commercial and residential 

ornamentals and lawns, recreational fields and golf courses. 

Summary of Usage Between 2006 and 2010, an average of 13,000 pounds active 

ingredient was applied on an average 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 and ground spray, including airblast, 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 

products4. 

Restricted Use No 

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular 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 

 

4

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

(http://oaspub.epa.gov/pestlabl/ppls.home). 
7

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 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county 

 Application timing (date of first application and application intervals) – 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 technical prohexadione calcium 

to the US market 

RECENT ACTIONS

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

ANTICIPATED RISK ASSESSMENTS 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 assessment 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 Environmental Fate, Ecological Risk, 

Endangered Species, and Drinking Water Exposure Assessment for Prohexadione Calcium and 

Prohexadione Calcium: Human-Health Assessment Scoping Document in Support of 

Registration Review. 

During registration review, the Agency anticipates the need to conduct a comprehensive 

ecological risk assessment, including an endangered species assessment, for all uses of 

prohexadione calcium. For human health, EPA anticipates the need to conduct revised 

residential, and occupational risk assessments during registration reviews. If toxicological 

endpoints or points of departure are 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 registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document. 
8

Table 4: Anticipated Risk Assessments 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 during registration review. 

The dietary assessment may needed to be updated in 

the future if toxicological 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 water concentration estimates were 

provided in the most recent EFED assessment. The 

estimated surface water concentrations were based on 

applications to turf at the 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 handler 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 residue 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 changes, or other new data 

received by the Agency that impact exposure 

estimates. 

Post-application Y A residential post-application assessment may be 

conducted based on the revised Residential SOPs, 

toxicological endpoint changes, 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 anticipated as a result of the 

revised 2012 Residential SOPs. These refinement of 

exposure estimates are anticipated 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) during 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 warrant further investigation. 

The Agency will continue to monitor the incident 

information and if a concern 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 already reported to the Agency. 

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

TIMELINE

EPA has created the following estimated timeline for the completion of prohexadione calcium’s 

registration review in Table 5 below. 
10

Table 5: Registration Review for Prohexadione 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 Draft Risk Assessments 2016 – July – Sept 

Registration Review Decision 

60-day Public Comment Period for 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 issue a Final Work Plan for the registration 

review of prohexadione calcium. 

 
11

Appendix – Additional Areas Considered 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 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 of MRLs 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: 

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 Act5

. In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for prohexadione calcium6. More information on impaired 

water bodies and TMDLs can be found at the Agency’s website7. 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 OPP’s Registration Review 

Risk Assessment and Management Process8 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 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.htm
12

ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been 

conducted for prohexadione calcium. The ecological risk assessment planned during registration 

review will allow the Agency to determine whether prohexadione calcium’s use 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. 

ENDOCRINE DISRUPTOR SCREENING PROGRAM: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for prohexadione calcium,

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), 

prohexadione calcium 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 with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 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 registration review, EPA will issue future EDSP 

orders/data call-ins, requiring the submission of EDSP screening assays for prohexadione 

calcium. For further information on the status of the EDSP, the policies and procedures, the list 
13

of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website9. 

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, 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 applicable 

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. 

 

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