Docket Number: EPA-HQ-OPP-2011-0482 www.regulations.gov



## Ancymidol Final Work Plan Registration Review
December 20113 ANCYMIDOL FINAL WORK PLAN

Introduction :

This is the Environmental Protection Agency’s (EPA’s) Final Work Plan for the registration review of ancymidol. This wo rk plan includes the expected registration review timeline. The work plan also addre sses public comments received concerning the Preliminary Work Plan (PWP) in the Summary Document , which was posted in the ancymidol registration review docke t (EPA-HQ-OPP-2011-0482), and any other comments concerning the ini tial docket postings. The Summary Document provided information on what EPA knows about the pest icide and what additional risk analyses and data or information the Agency believes are needed to make a registration review

decision.

The Agency is implementing the registra tion review program and will review each registered pesticide every 15 years to determin e whether it continues to meet the Federal Insecticide, Fungicide, and R odenticide Act (FIFRA) standard for registration. Changes in science, public policy, and pesticide use practices will occur over time. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and pract ices change, all registered pe sticides continue to meet the statutory standard. The public phase of registration review begins when the initial docket is opened for each case. Inform ation on this program is provided at: http://www.epa.gov/oppsrr d1/registration_review/

.

Ancymidol (Case 3017) is a plant growth re gulator registered fo r treating containergrown herbaceous plants, ornamental w oody shrubs, and bedding plants grown in greenhouses and other plant bedding areas for commercial production. There are no food/feed or residential uses of products containing this active ingredient. Growth regulator effects produced by ancymidol are the result of inhibition of gibberellin biosynthesis. Since gibberellin promotes growth, treatment with ancymidol induces a more compact growth form by suppressing growth between nodes. Ancymidol was the subject of a Reregistration E ligibility Decision (RED), which was completed in June
1995.

Available data suggest use of ancymidol is minimal. For the primary use, inside nurseries/greenhouses, less than 20 pounds we re used per year in 1999, 2002, 2004, and
2006. To better understand the e xposure potential for ancymidol, given the current uses and application rates, the Agency has devel oped an estimate of environmental exposure (see “Equivalent outdoor” per-ac re application rates for ancymidol used on containergrown greenhouse transplants , dated November 28, 2011). The Agency is in the process of determining how these estimates may cha nge the current ecological risk assessment approach and the associated data requirements. If the Agency alters its risk assessment approach or data needs for the ancymidol registration review, it will document these changes in an amended final work plan that will be announced through a Federal Register notice.4 Comments Received on Preliminary Work Plan :

The ancymidol registration review docket was open for a 60-day comment period beginning on June 29, 2011. The Agency received one comment during the public comment period. There are no changes to the ri sk assessment, data needs or the timeline detailed in the ancymidol PWP. EPA al so solicited comments, through the PWP, on three specific topics: environm ental justice, water body impairment, and trade irritants.
No comments or information were receive d during the comment period concerning these issues. Further, this document makes final th e work plan for the ancymidol registration review process.

Physicians Committee for Responsible Medicine (PCRM) Comments :

PCRM supports three measures which they suggest may reduce the number of test animals needed for two separate studies wh ich the Agency will require for ancymidol.

 PCRM supports a revised OECD test gui deline (TG223) for avian acute oral toxicity testing for passerine and waterfowl or upland game species.

 PCRM supports use of a “limit test” appr oach for the acute toxicity study for both freshwater and estuarine/marine species.

 PCRM encourages the use of quantit ative structure–activity relationship
( (Q)SAR) data either in place of, or in addition to, the fish experimental data.

EPA Response:

OECD test guideline :

The Agency recently completed its review of the OECD validation report to determine if the TG223 effects endpoints and dose/response information adequately address the purposes of the avian acute oral data require ment as described in 40 CFR Part 158 and 40 CFR Part 161. The Agency determined that a study conducted using TG223 may be classified as ‘acceptable’ if it is scientif ically valid; is c onducted using the ‘LD 50 - slope test’ or ‘limit dose test' guidelines (the LD 50 - only test is not adequate for fulfilling data requirements); and meets all of the following criteria:

 The study is conducted using bobwhite quail (other test species may be acceptable if they have low background mortality in the laboratory and do not regurgitate during the study). The background mortalit y data for the species in question should be available from the submitting laboratory at the time of the Agency
review.5  The chemical being tested doe s not cause delayed effects.

 For a ‘limit dose test,’ the study is to be conducted at 2,000 mg a.i./kg-bw or the environmentally-relevant concentr ation (whichever is greater).

 For the ‘LD 50 - slope test,’ the raw data and results are to be submitted electronically using the SEquential DE sign Calculator (SEDEC) (the Excel calculator that determines the placement of doses during testing and is used to

estimate the LD 50 , slope and confidence limits for TG223 studies).

 The study meets the same validity requirements as Guideline 850.2100 (e.g.

, a study should be invalidated if > 10% of the controls die).

 Control birds are not added dur ing the course of the study.

Studies that deviate from th e above criteria may be clas sified as ‘acceptable’ or ‘supplemental’ if they are considered adequate for use in risk asse ssment or ‘invalid’ if they are not scientifically sound; however, any TG223 study th at deviates from the above
criteria will need additional evaluati on by the Agency to confirm the study’s

classification.

Agency use of ‘limit tests’ :

Limit tests may be acceptable if no mortality occu rs at test concentra tions that are 20-fold higher than peak estimated environmental concen trations. A factor of 20 is used because the endangered species level of concern is 0.05, which represen ts a value that is 20-fold
lower than the LC 50

.

Agency use of (Q)SAR data :

EPA considers SAR/QSAR (Structure Activity Relationship/Quantitative SAR) predicted estimates to address data requirements on a case-by-case basis. Uncertainty in those predicted estimates may be higher than thos e from empirical data. Although (Q)SAR estimates may be considered in a weight-of-evidence analysis, confirmatory tests are generally required when risks cannot be c onfidently dismissed based solely on the (Q)SAR estimates.

Risk Assessment and Data Needs :

The Agency will conduct a comprehensive ec ological risk assessment, including an endangered species assessment for all uses of ancymidol. The Agency will require data in order to conduct the planne d ecological risk assessment. Below is a summary of the ecological and human health i ssues relevant to the regist ration review of ancymidol:6 Ecological Risk:

 The most recent ecological risk assessment for ancymidol was completed in 1995 in support of the RED.

 As noted earlier, available data suggest use of ancymidol is minimal. The Agency is in the process of ev aluating the environmental exposure potential for ancymidol, given the current uses and app lication rates. Depending on the results of this evaluation, the current risk asse ssment approach and the associated data requirements may change.

 EPA may conduct an ecological risk asse ssment for the indoor and outdoor uses of ancymidol during registration review . The Agency is evaluating whether indoor uses (i.e., greenhouse plants transpla nted into ornamental beds) may result in sufficient environmental exposure to n ecessitate an ecological risk assessment.

 The planned assessment will incorpor ate the most up-to-date modeling methodologies, updated assessment endpoi nts, and data submitted under the registration review data call-in.

 The Agency has not conducted an ecol ogical risk assessment that supports a complete endangered species determinati on for ancymidol. The ecological risk assessment planned during registration revi ew will allow the Agency to determine whether ancymidol’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 (FWS) a nd/or National Marine Fisheries Service (NMFS) (the Services), as appropriate.

 Data gaps exist in the environmental fate and toxicity databases for ancymidol. In the ecological risk assessment comp leted for the 1995 RED, the Agency concluded that, because of the limited treated acreage, minor use sites (e.g., ornamental flowers and shrubs), and low toxicity cited in the submitted studies, adverse effects to birds, mammals, aquatic organisms and non-target plants were expected to be minimal. Accordingly, no additional ecological data were required
at that time. Based on current environm ental fate and ecological risk assessment standards, data are needed for the regist ration review assessment of ancymidol. However, depending on the results of the Agency’s evaluation of the environmental exposure potential for an cymidol given the current uses and application rates, the data requirements may change.

 Current formulations with labeled outdoor uses for spray, drench, and chemigation applications do not specif y maximum application rates per plant type. Maximum annual application rates per pot size or appl ication rates per growing season, where appropriate, on a chemical-weight basis need to be7 specified; also a maximum number of seque ntial applications per plant type need to be defined. In the absence of this occurring, the Agency will employ conservative assumptions in the e ndangered species risk assessment.

 The Agency will require the following environmental fate and environmental effects data during registra tion review for use in ecological assessment, including an endangered species assessment of ancymidol:

o Guideline (GLN) No. 835. 2240 – Photodegradation in Water

o GLN No. 835.2410 – Photodegradation in Soil

o GLN No. 835.4100 – Aerobi c Soil Metabolism

o GLN No. 835.4200 – Anaerobic Soil Metabolism

o GLN No. 835.4300 – Aerobic Aquatic Metabolism

o GLN No. 835.4400 – Anaerobic Aquatic Metabolism

o GLN No. 835.6100 – Terrestrial Field Dissipation

o GLN No. 835.6200 – Environmental Chem istry Analytical Methods for
Residues in Water and Sediment and Independent Laborat ory Validation

o GLN No. 850.2100 – Avian Oral Toxicity (passerine and waterfowl or upland game)

o GLN No. 850.2200 – Avian Dietary T oxicity Test (waterfowl)

o GLN No. 850.2300 – Avian Reproducti on Test (waterfowl and upland game species)

o GLN No. 850.1025 – Oyster Ac ute Toxicity Test

o GLN No. 850.1035 – Mysid Acute Toxicity Test

o GLN No. 850.1045 – Penaeid Ac ute Toxicity Test

o GLN No. 850.1055 – Bivalve Ac ute Toxicity Test

o GLN No. 850.1075 – Fish Acute T oxicity Test (Freshwater)

o GLN No. 850.1075 – Fish Acute Toxici ty Test (Estuarine/Marine)

o GLN No. 850.1300 – Daphnid Chr onic Toxicity Test

o GLN No. 850.1400 – Fish Early-Life St age Toxicity Test (Freshwater)

o GLN No. 850.4100 – Nontarget Area P hytotoxicity Tier II, Seedling Emergence

o GLN No. 850.4150 – Nontarget Area P hytotoxicity Tier II, Vegetative Vigor

o GLN No. 850.5400 – Nontarget Area Phyt otoxicity Tier II, Aquatic Plant Growth (Algal Plants)

 Please refer to Registration Review – Preliminary Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Ancymidol , dated March 28, 2011, located in the docket, for a detailed discussion of thes e anticipated risk assessment and data

needs.8 Human Health Risk :

 The most recent human health risk a ssessment was completed in 1995 in support
of the RED. This assessment evalua ted occupational exposures only, as no
food/feed or residential uses are registered for ancymidol.

 The Agency has evaluated the status of the human health assessments for ancymidol and determined that no additional human health exposure or hazard information are required to support the registration review of ancymidol.

 Please refer to the Ancymidol. Human Health Assessment Scoping Document in Support of Registration Review , dated June 7, 2011, located in the docket, for a detailed discussion of the anticipated ri sk assessment and data needs for human

health.

Endocrine Disruptor Screening Program :

As required by FFDCA section 408(p), ancymidol is subject to the endocrine screening part of the Endocrine Disrupt or Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingred ients) may have an effect in humans or wildlife similar to an effect produced by a “natur ally occurring estrogen, or othe r such endocrine effects as the Administrator may designate.” The ED SP 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 substa nce 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 inte ract with E, A, or T hormonal systems will proceed to the next stage of the EDSP wher e EPA will determine which, if any, of the Tier 2 tests are necessary based on the availa ble data. Tier 2 te sting is designed to identify any adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between th e 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. Ancymidol is not among the group of 58 pesticid e 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 ancymidol. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, futu re lists, the test guide lines and the Tier 1 screening battery, plea se visit our website: http://www.epa.gov/endo/

.9 Timeline :

EPA has created the following timeline for completion of the registration review for ancymidol.

Registration Review for Ancymido l – Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and Public Co mment Period 2011 – June Close Public Comment 2011 – August Case Development

Final Work Plan 2011 – December Issue DCI 2012 – July – Sept. Data Submission 2014 – July – Sept. Open Public Comment Period for Draft Risk Assessments 2016 – Jan. – March Close Public Comment Period 2016 – April – June Registration Review Decision Open Public Comment Period for Proposed Registration Review

Decision 2016 – July – Sept.

Close Public Comment Period 2016 – Oct. – Dec. Registration Review Decision and Begin Post-Decision Follow-up 2017 Total (years) 6

Next Steps :

The Agency plans to develop a Data Call-In No tice for this pesticide and plans to issue it
in mid-2012. This new information will be used to conduct risk assessments for ancymidol uses.10 Summary of Data Gaps – Ancymidol :

The table below summarizes the data requirements for ancymidol. The Agency will require the following environmental fa te and environmental effects data during registration review to support an ecological assessment of ancymidol. Please refer to Registration Review – Preliminary Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Dr inking Water Exposur e Assessments for Ancymidol for a detailed discussion of these upcoming risk assessment and data needs.

Guideline

Number Study Title Test
Material Estimated

Timeframe

835.2240 Photodegradation in Water TGAI 1 12 835.2410 Photodegradation in Soil TGAI 12

835.4100 Aerobic Soil Metabolism TGAI 24

835.4200 Anaerobic Soil Metabolism TGAI 24 835.4300 Aerobic Aquatic Metabolism TGAI 24 835.4400 Anaerobic Aquatic Metabolism TGAI 24 835.6100 Terrestrial Field Dissipation TGAI 24

835.6200 Aquatic Field Dissipation 2 TGAI 12

850.2100 Avian Oral Toxicity (p asserine and waterfowl or upland game) TGAI 12

850.2200 Avian Dietary Toxicity Test (waterfowl) TGAI 12

850.2300 Avian Reproduction Test (waterfowl and upland game species) TGAI 24

850.1025 Acute Toxicity Estuarine/Marine Organisms (Oyster) TGAI 12

850.1035 Mysid Acute Toxicity Test TGAI 12

850.1045 Penaeid Acute Toxicity Test TGAI 12 850.1055 Bivalve Acute Toxicity Test TGAI 12

850.1075 Fish Acute Toxicity Te st (Estuarine/Marine) TGAI 12

850.1075 Fish Acute Toxicity Test (Freshwater) TGAI 12

850.1300 Daphnid Chronic Toxicity Test TGAI 12

850.1400 Fish Early-Life Stage Toxicity Test (Freshwater) TGAI 12

1 Technical Grade Active Ingredient (TGAI).

2 Only the Environmental Chemistry Methods and In dependent Laboratory Validation portions of the study are needed.11 Guideline

Number Study Title Test
Material Estimated

Timeframe

850.4100 Nontarget Area Phytotoxic ity Tier II, Seedling Emergence 3 TEP 4 12

850.4150 Nontarget Area Phytotoxicity Tier II, Vegetative Vigor 3 TEP 12

850.5400 Nontarget Area Phytotoxic ity Tier II, Aquatic Plant Growth (Algal Plants) 3 TEP 12

3 A Tier II study is expected to be required. The DC I expected to be issued will provide that a Tier I plant study may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I study would necessitate conduct and submission of a Tier II study as well.

4 Typical End-use Product (TEP).