2 

### Daminozide Interim Decision

- Table of Contents

**Contents**
I. INTRODUCTION

................................ ................................ ................................ ..................... 4

II. USE AND USAGE

................................ ................................ ................................ ................... 6

III. SCIENTIFIC ASSESSMENTS

................................ ................................ ................................ 6
A. Human Health

................................ ................................ ................................ ......................... 6
1. Risk Conclusions

................................ ................................ ................................ ........... 6
2. Human Incidents

................................ ................................ ................................ ............ 8
3. Tolerances

................................ ................................ ................................ ...................... 8

B. Ecological

................................ ................................ ................................ .............................. 8
1. Risk Conclusions

................................ ................................ ................................ ........... 9
2. Pollinator Studies and Assessment

................................ ................................ .............. 10
3. Ecological Incidents

................................ ................................ ................................ .... 11
C. Benefits

................................ ................................ ................................ ................................ 11 D. Endangered Species Assessment

................................ ................................ ........................ 1 1 E. Endocrine Disruptor Screening Program

................................ ................................ ............. 1 2

IV. INTERIM REGISTRATION REVIEW DECISION

................................ .............................. 1 3

A. Risk Mitigation and Regulatory Rationale

................................ ................................ .......... 1 4

B . Endangered Species

................................ ................................ ................................ ............. 1 4

V. NEXT STEPS

................................ ................................ ................................ .......................... 153 References: This Interim Decision summarizes the Environmental Protection Agency's current position based on the following documents:

1. Preliminary Ecological Risk Assessment for the Registration Review of Daminozide

. Christine Hartless and James Lin. 4 December 2014

.

2. Daminozide (Alar). Draft Human Health Risk Assessment for Registration Review . Douglas A. Dotson, Linnea Hansen, and Zaida Figueroa. 8 December 2014.

3. Updated Review of Daminozide (Alar) Incident Reports

. Monica Hawkins and Jessie Cordova

. 30 January 2009.

4. Qualitative Assessment of Daminozide Use in Ornamental Plant Production (DP# 426348) (PC Code 035101). Sunil Ratnayake and Stephen Smearman. 18 May 2015.

5. Daminozide Proposed Interim Registration Review Decision . 22 June 2015.

These and other supporting documents for the daminozide registration review case may be found in the docket EPA

- HQ

- OPP

- 2009

- 0242 at http://w ww.regulations.gov

.4 

### I. INTRODUCTION

This document is the Environmental Protection Agency’s (EPA or the Agency) Interim Registration Review Decision for daminozide (case 0032 , PC 035101 ) and is being issued pursuant to 40 CFR sections 155.56 and 155.58

. A registration review decision is the Agency's determination whether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it determines it to be app ropriate, a n I nterim R egistration R eview D ecision before completing a registration review. Among other things, the I nterim R egistration R eview D ecision may : 1) require new risk mitigation measures ; 2) impose interim risk mitigation measures ; 3) identify ad ditional data or other information required to complete the review ; and 4) include schedules for submitting the required data, conducting the new risk assessment and completing the registration review. For further information on daminozide , additional docu ments can be found in EPA’s public docket (EPA

- HQ

- OPP

- 2009

- 0242 ) at www.regulations.gov

. FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the continuous review of existing pesticides. All pesticides distributed or sold in the United States generally must be registered by the EPA based on scientific data showing tha t they will not cause unreasonable risks to human health or to the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess and reduce risk evolves and as policies and pr actices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects. Changes in science, public
p olicy, and pesticide use practices will occur over time. Through the registration review program, the Agency p eriodically re

- evaluates pesticides to make sure that as these changes occur, products in the marketplace can continue to be used safely. Information on this program is provided at http://www2.epa.gov/pesticide

- reevaluation/registration

- review

- process

. In 2006, the Agency implemented the registration review program pursuant to FIFRA section 3(g) and will review each registered pesticide every 15 years to determine whethe r it continues to meet the FIFRA standard for registration.

EPA is issuing an interim registration review for daminozide so that it can (1) move forward with aspects of the registration review that are complete and (2) implement interim risk mitigation. The Agency is currently working with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service to develop methodologies for conducting national endangered species assessments for pesticides. Therefore, although EPA has not yet fully ev aluated risks to threatened and endangered species, the Agency will complete its endangered species assessment and any necessary consultation with the S ervices for daminozide prior to completing the daminozide registration review. Likewise, the Agency wil l complete endocrine screening for daminozide , pursuant to the Federal Food

, Drug

, and Cosmetic Act (FFDCA) section 408(p), before completing this registration review. Last, EPA will determine whether additional pollinator exposure and effects data are ne cessary to make a final registration review decision for daminozide and issue a data call

- in (DCI) to obtain any such data prior to completing the daminozide registration review.

Daminozide is a systemic plant growth regulator (PGR) used to control the development of commercially grown container plants by changing their growth habit

, usually by making a plant sho rter and more densely packed. It is registered for use in nurseries, shadehouses, and5 greenhouses, applied as a foliage sp ray that is systemically distributed throughout the plant. Daminozide has no registered food uses . Additionally, t her e are no registered residential approved for daminozide. The Reregistration Eligibility Decision document (RED) for daminozide was comple ted in September 1993

. This document is organized in five sections: the Introduction, which includes this summary and a summary of public comments and EPA’s response; Use and Usage, which describes how and why sulfentrazone is used and summarizes data on its use; Scientific Assessments, which summarizes EPA’s risk assessment, any revisions, and risk conclusions; Interim Registration Review Decision, which describes the mitigation measures proposed to address risks of concern and the regulatory rationale fo r EPA’s registration review decision; and, last, the Next Steps and Timeline for completion of this registration review.

Pursuant to 40 CFR section 155.50, EPA formally initiated registration review for daminozide (case 0032 )

. The following summary highlights significant events that have occurred during the registration review of daminozide and can be found in EPA’s public docket

, EPA

- HQ

- OPP

2009

- 0242 , accessed at www.regulations.gov

.

• Jun e 24, 2009

– Public ation of d aminozide Preliminary Work Plan (PWP) for a 60

- day public comment period . The P reliminary W ork P lan (PWP) was accompanied by the scoping document and problem formulation.

• Dec ember 3, 2009

– A Final Work Plan (FWP) for d aminozide was issued . N o public comments were received during the 60

- day comment period for the daminozide PWP. Therefore, the FWP did not modify the PWP.

• Sep tember 22, 2010

– Generic Data Call

- In ( GDCI

- 035101

- 915 ) for daminozide was issued.

• December 24, 2014

– The Agency publ ished the Preliminary Ecological Risk Assessment for the Registration Review of Daminozide and Daminozide (Alar). Draft Human Health Risk Assessment for Registration Review

. Two comments were received during the comment period.

• June 22, 2015

– The Agency publish ed the Daminozide Proposed Interim Registration Review Decision for a 60

- day public comment period.

o EPA also publish ed the following use/usage and benefits document regarding daminozide: Qualitative Assessment of Daminozide Use in Ornamental Plant P roduction (DP# 426348) (PC Code 035101). 18 May 2015.

o No comments were received during the 60

- day comment period for the Daminozide Proposed Interim Registration Review Decision

.

• November 2015

– The Agency is now publishing the Daminozide Interim Registration Review Decision in docket number EPA

- HQ

- OPP

- 2009

- 0242.6 

### II

. USE AND USAGE

Daminozide is a PGR registered for use in control ling the development of commercially grown container plants by changing their growth habit; usually by making a plant sho rter and more densely packed. It is u sed in nurseries, shadehouses, and greenhouses, applied as a foliage spray that is systemically distr ibuted throughout the plant. Daminozide has no registered food uses

. Generally, daminozide is applied inside of greenhouses, so there is little or no potential for off

site drift. For additional details regarding use and usage information for daminozide , see the document, Qualitative Assessment of Daminozide Use in Ornamental Plant Production (DP# 426348) (PC Code 035101) , available in EPA’s public docket

, EPA

- HQ

- OPP

- 2009

- 0242

, access ible a t www.regulations.gov

.


### III. SCIENTIFIC ASSESSMENTS

A. Human Health

A summary of the Agency’s human health risk assessment is presented below. The Agency used the most recent Agency science policies and risk assessment methodologies to prepare a qua nti tative risk ass essment in support of the registration review of daminozide. For a detailed discussion of the human health assessment for daminozide

, please refer to Daminozide (Alar). Draft Human Health Risk Assessment for Registration Review dated December 8, 2014 , whi ch is

a vailable i n the public docket EPA

- HQ

- OPP

- 2009

- 0242 and is accessible via http://www.regulations.gov/

.

1. Risk Conclusions

Dietary Assessment As there are no registered uses expected to result in dietary exposure, and there is no expectation that residues will be present in ground or surface water sources of drinking water, dietary risk is not expected from currently registered uses of daminozide.

Residential Assessment There are no registered residential uses or commercial uses at residential sites associated with daminozide, and the current uses are not expected to result in spray drift. The Agency considered post

- application risk from treatments to commercial ornamentals that may be purchased and used in residential settings, but exposure from this scenario was determined to be negligible and not of concern. As there is no residential exposure expected from currently registered uses of daminozide, residential risk is not anticipated.

Aggreg ate Assessment As there are no registered uses that result in dietary or residential exposures, an aggregate risk assessment was not conducted. Aggregate risk is not expected

.

Cumulative Assessment7 Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to daminozide and any other substances

. D aminozide does not appear to produce a toxic metabolite produced by other substances , so a cumulative risk assessment has not been conducted.

Non

- Cancer Occupational Assessment No target organs for non

- cancer effects were identified in subchronic or chronic dietary studies on daminozide. Therefore, no non

- cancer endpoints were selected for r isk assessment. Daminozide is poorly absorbed in mammals following oral or dermal exposure; exhibits low toxicity via oral, dermal, and inhalation routes of exposure; does not show evidence of either immunotoxicity or neurotoxicity; and is not irritating to the skin, nor is it an eye irritant or a skin sensitizer. No incidents or pre

- natal susceptibility effects were identified.

Occupational non

- cancer, occupational handler, and post

- application risk estimates were not quantitatively assessed because no dermal or inhalation non

- cancer toxicological endpoints of concern were identified. While occupational handler and post

- app lication exposure is possible,
t he Worker Protection Standard for Agricultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) (restrictions associated with pesticide applications)]. These requirements are considered to be protective of any p otential low

- level

non

- cancer post

- application inhalation exposure that could result from these types of applications . However, in the case of daminozide, there is no non

- cancer risk associated with these applications due to the lack of toxicity via the d ermal and inhalation routes of exposure.

Cancer Risk Daminozide is classified as a B2, probable human carcinogen. A cancer potency factor (Q1*) of 0.0087 (mg/kg /day)

- 1 ) was calculated for daminozide based on an increased incidence of lung tumors in mice. Registered daminozide use scenarios were assessed f or their potential cancer risk. At the maximum single application rate for daminozide of 0.063 lb ai/gal, the cancer risk estimate calculated is 4x10

- 5 for occupational workers conducting handler activit ies. At the lowest labeled single application rate for daminozide of 0.0084 lb ai/gal, the cancer risk estimate for occupational workers conducting handler activities is 6x10

- 6 . These values represent the range of the occupational cancer risk estimate for daminozide when applied in either a nursery or shadehouse using a mechanically pressurized handgun, assuming that the same commercial applicator would use daminozide up to 30 days per year (with a retreatment interval of every 1

- 2 weeks) for 35 years out of a 78 year lifespan, and applying a total of 1,000 gallons of product per day

. The PPE required on daminozide labels includes a single layer of clothing and no respirator. Because daminozide applications using a mechanically pressurized handgun are tho se with the highest cancer risk estimate s , this use scenario is protective of cancer risk for daminozide uses applied via a backpack sprayer or manually

- pressurized handwand.

A ll daminozide registrations approved for use on ornamental plants include label language advising different ranges for the concentration of mixed solution to use when appl ying daminozide to different species of plants. In certain cases, d ifferent application concentrations are also suggested for multiple uses ty pes on the same target plant; for example, daminozide uses

on cut vers u s potted chrysanthemums

. Due to the wide range of application rates for8 daminozide, it is unlikel y that applicators will be applying daminozide solely at the maximum single application rate for the full length of a theo retical 35

- year exposure period . Therefore, the Agency is not identifying cancer risks of concern for daminozide in this interim decision

. The daminozide degradation product

, unsymmetrical dimethyl hydrazine (UDMH)

, is also classified as a B2, pro bable human carcinogen, and has a cancer potency factor of 0.46 (mg/kg/day)

- 1 based on an increased incidence of hemangiosarcomas in mice

. In view of the potential formation of UDMH during storage of tank mix, all end

- use prod ucts have a restriction statement on their labels that reads: “Solutions prepared should not be held for more than 24 hours.” Total occupational exposure to UDMH is expected to be very low because of the low levels of UDMH present (up to 0.1%) in the tank mix at 24 hrs (the label

- directed limit of storage time). This incremental increase also represents a small percentage of the total internal exposure to UDMH from metabolism of daminozide, estimated at 1% of the dose. Therefore, the cancer risk from exposu re to UDMH is not of concern.

2. Human Incidents As reported in the 2009 document, Updated Review of Daminozide (Alar) Incident Reports

, no human health incidents were found occurring in the United States from 2002 to 2009 for the single chemical daminozide. Additionally, the Agency’s 2014 report Daminozide (Alar). Draft Human Health Risk Assessment for Registration Review reports that updated incident analyses of the Main and Aggregate IDS from January 1, 2009 to December 2, 2014, as well as the National Institute of Occupational Safety and Health Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR

- Pesticides) from 1998 to 2010, found only one incident. The case was of low severity and involved multiple chemicals, one of which was daminozide. Based on the continued low frequency and severity of incident cases reported for daminozide, there does not appear to be a concern at this time that would warrant further investigation.

3. Tolerances As there are no food uses for daminozide

, there are no established food tolerances for this chemical.

B. Ecological

A summary of the Agency’s ecological risk assessment is presented below. The Agency used the most updated Agency science policies and risk assessment methodologies to prepare a
q ua nt itative risk assessment in support of the registration review of daminozide

. For a detailed discussion of the ecological assessment for daminozi de see the Preliminary Ecological Risk Assessment for the Registration Review of Daminozide dated December 4, 2014

, which is available i n the public docket EPA

- HQ

- OPP

- 2009

- 0242 and is accessible via http://www.re gulations.gov/

. The Agency also completed a screening

- level endangered and threatened (listed) species assessment for daminozide and made a No Effects (NE) determination for daminozide to listed species of fish, aquatic

- phase amphibians (that do not have terrestrial

- phases), aquatic invertebrates, aquatic plants, terrestrial invertebrates, monocots (in terrestrial and wetland9 habitats), and dicots (in terrestrial and wetland habitats) that do not rely upon birds, terrestrial

phase amphibians, reptiles, and/or mammals (for food or shelter) . The Agency is currently working with its federal counterparts and other stakeholders to implement an interim approach for assessing potential risk to listed species and their designated critical habitats. Once the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats are finalized, the Agen cy will complete its endangered species assessment for daminozide

. A t currently labeled rates

, r isk due to use of daminozide cannot be precluded for listed and non

- listed non

- target birds, reptiles, terrestrial

- phase amphibians and mammals without further analysis. A final decision on the daminozide registration review case will occur after EDSP FFDCA section 408(p), complete pollinator, and ESA determinations have been made.

1. Risk Conclusions For indoor uses ( i.e ., enclosed greenhouse) of daminozide , dir ect adverse effects are unexpected for all non

- target plant and animal species

. For outdoor uses ( i.e., unenclosed nurseries and shadehouses) of daminozide, currently labeled rates of daminozide pose a potential risk to non

target terrestrial animals, including birds, reptiles, terrestrial

- phase amphibians and mammals. E cological risk finding s f o r daminozide are summarized as follows:

Mammals Definitive toxicity endpoints could not be determined for acute or chronic rat studies. Using dose

based intak e estimates, acute exposure is less than the highest tested acute toxicity level and no effects were observed in the toxicity study; acute risk to mammals from currently labeled use rates of daminozide is low

. However, since the potential exposure is higher than the highest tested dose, chronic risk to mammals eating on treated sites cannot be precluded.

Birds Definitive toxicity endpoints could not be determined for acute bird studies , and no mortality was observed

. As a pplication rates on labels ar e higher than exposure levels evaluated in the avian toxicity tests, acute risk potential cannot be precluded. Daminozide may pose chronic risk concerns for birds feeding on short grass, tall grass, broadleaf plants, and arthropods feeding at the treated sites

. Aquatic Animals and P lants Acute risk is not expected for fish as the most conservative acute endpoint yielded a risk quotient that does not exceed the level of concern. Acute risks to invertebrates and non

- vascular plants are presumed low as the estimated environmental concentration (EEC) was approximately 1000 times less than the highest test concentrations. Daminozide is not expected to bioaccumulate in fish . A risk quotient was not determined for chronic risk to fish due to a lack of toxicity data, but effects to growth and reproduction are not expected because the chr onic toxicity of daminozide would have to be at least 8

, 600 times greater than the acute toxicity.

T erre strial Invertebrates and P lants D aminozide is practically non

- toxic to honey bees on an acute exposure basis. No definitive toxicity endpoints were available for honeybees; however, due to low toxicity

, the potential for adverse effects f r o m contact exposure to daminozide residues on plants is expected to be low. All calculated10 risk quotients for terrestrial pl ants were less than the level of concern ; therefore, off

- field drift risks
to non

- target plants is presumed to be low.

2. Pollinator Studies and Assessment

When initially scoping the registration review for daminozide, EPA did not identify the need for
any additional studies to evaluate potential effects on pollinators. However, since the issuance of the June 2014 Guidance for Assessing Pesticide Risks to Bees [1]

, EPA has begun to require these data where applicable. EPA is currently determining whether add itional pollinator data are needed for active ingredients in registration review whose dockets opened prior to June 2014. For those active ingredients where EPA determines that additional pollinator exposure and effects data are necessary to help make a fi nal registration review decision, EPA intends to issue a DCI to obtain these data. In the near future, EPA will provide further information and guidance on this effort. The pollinator studies that could be required are included in Table 1 below. The Agenc y will require data it believes are needed to help inform the pollinator risk
assessment.

Table 1. Potential Pollinator Data Requirements

Guideline # Study
850.3020* Acute contact toxicity study with adult honey bees
850.3030* Honey bee toxicity of residues on foliage
850.3040** Field testing for pollinators
Non

- Guideline* (OECD 213) Honey bee adult acute oral toxicity

Non

- Guideline* (OECD 237) Honey bee larvae acute oral toxicity

Non

- Guideline* Honey bee adult chronic oral toxicity
Non

- Guideline* Honey bee larvae chronic oral toxicity
Non

Guideline** Residues in pollen and nectar/field residue analysis

Non

Guideline** (OECD 75) Semi

- field testing for pollinators (tunnel or colony feeding studies)

*Tier 1 (Laboratory

- based studies) **Tier 2 and 3 (Semi

- field and full field colony

- level studies) The need for a higher tier test for pollinators will be determined based upon lower

- tiered tests and/or other lines of data and the need for a refined pollinator risk assessment.

[1] http://www2.epa.gov/sites/production/files/2014

- 06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf11 3. Ecologic al Incidents

The Ecological Incident Information System (EIIS), the Avian Incident Monitoring System (AIMS) and aggregate incident databases were searched for incident reports on April 30, 2014. No ecological incidents were reported in any of the evaluate d databases.

C. Benefits

Daminozide is a systemic plant growth regulator (PGR) registered for use in control ling the development of commercially grown container plants by chang ing their growth habit. Damino z i de reduce s the internode length of ornamental plants by inhibiting the synthesis of gibberellic acid, resulting in a n ornamental plant that is shorter and more densely packed. Controlling plant size is an important aspect of greenhouse plant production. Reduction o f plant size maximizes production of ornamental plants per unit area of a greenhouse. Also, it improves the efficiency of certain greenhouse activities such as irrigation, fertilization, and handling. In addition, the reduction of interrnodal length minimi zes plant damage during shipping and handling and helps to produce more visually pleasing compact plants with deeper green coloration.

Compared to the many other plant growth regulators, daminozide has a fairly short residual effect, typically lasting one to four weeks depending on the application rate and the environmental conditions. This short duration of residual activity m ay be desirable for young plant production, since the growth inhibition may not be desirable after transplanting. For additional d etails regarding use and usage information for daminozide, see the document, Qualitative Assessment of Daminozide Use in Ornamental Plant Production (DP# 426348) (PC Code 035101) , available in EPA’s public docket, EPA

- HQ

- OPP

- 2009

- 0242, accessible at www.regulations.gov

.

D. Endangered Species Assessment

In November 2013, the EPA, along with the Services and the USDA, released a summary of their joint Interim Approaches for assessing risks to endangered and threate ned (listed) species from pesticides. The Interim Approaches were developed jointly by the agencies in response to the National Academy of Sciences’ (NAS) recommendations and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. The NAS report 1 outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA.

The joint Interim Approache s were released prior to a stakeholder workshop held on November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and State

- FIFRA Issues Research and Evaluation Group ( S FIREG) meetings

. The agencies also held stakeholder workshop s in April and October 2014, allowing additional opportunities for stakeholders to comment on the Interim

1 http://www.nap.edu/catalog.php?record_id=1834412 Approaches. Additional workshops are planned to enhance stakeholder involvement. As par t of a phased, iterative process for developing the Interim Approaches, the agencies will also consider public comments on the Interim Approaches in connection with the development of upcoming Registration Review decisions. The details of the joint Interi m Approaches are contained in the white paper “ Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report” 2 , dated November 1, 2013.

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, the ecological risk assessment supporting this Interim Decision for daminozide does not contain a complete ESA analysis that includes effects determinations for specific listed species or designated critical habitat. Although EPA has not yet completed effects determinations for specific species or habitats, for this preliminary assessment EPA conducted a screening

- level assessment for all taxa of non

- target wildlife and plants that assumes for the sake of the assessment that listed species and designated critical habitats may be present in the vicinity of the applicat ion of daminozide . This screening level assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific methods being developed by the agencies have been fully vetted. While the agencies continue to develop a common method for ESA analysis, the regulatory section of the Interim Registration Review Decision document will describe the level of ESA analysis completed for this particular registration review case. Once the agencies h ave fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses for daminozide as part of completing this regi stration review.

E

. 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 tox icity, 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, developmen tal and reproductive effects in different taxonomic groups. As part of its most recent registration decision for daminozide , 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), daminozide is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

2 http://www.epa.gov/espp/2013/nas.html13 EPA has developed the EDSP to determine whether certain substances (including pesticide

ac tive 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 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 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 ingred ients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 3 and includes some pesticides 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. 4

In this interim decision , EPA is making no human health or environmental safety findings associ ated with the EDSP screening of daminozide . Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.



### I V

. INTERIM REGISTRATION REVI EW DECISION

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Interim Registration Review Decision. Except for the EDSP

, ESA , and pollinator components of this case, the Agency has made the following Interim Registration Review Decision: (1) no additional data are required at this time; and (2 ) changes to the affected registrations and their labeling are not needed at this time. No changes we re made to the Agency’s decision for daminozide since the publication of the Daminozide Proposed Interim Registration Review Decision

. In this interim registration review decision, EPA is making no human health or environmental safety findings associated with the EDSP screening of daminozide, nor is it making a complete endangered species finding. The Agency’s final registration review decision for daminozide will depend upon both the result of an ESA Section 7 consultation with the Services, and an EDSP FFDCA section 408(p) determination.

3 See http://w ww.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

4 http://www.epa.gov/endo/14 A. Risk Mitigation and Regulatory Rationale

The Agency is not proposing any human health mitigation measures for daminoz ide at this time. Current label language, such as the restriction of a 24

- hour storage limit for t ank mixes containing daminoz i de, is adequate to mitigate occupational risk from exposure to daminozide and its degradate, UDMH

.

D aminozide does not raise significant concern for ecological risks. Daminozide is applied by a drench/foliar spray applicatio n method to ornamentals in nurseries, shadehouses, and greenhouses, a use pattern which greatly minimizes the potential for spray drift. Furthermore

, d aminozide is most efficacious when applied under still conditions , and it is the Agency’s understanding t hat it is a standard practice to time daminozide applications to take place under still, humid conditions, which further reduces the pote ntial for spray drift. Finally, the two end

use product labels that allow for uses outside of enclosed greenhouses bo th restrict use in production areas not under cover to containerized ornamental plant s , which are unlikely to be a major food source for non

- target organisms such as birds

.
As described in the 2014 daminozide ecological risk assessment, no chronic or reproductive effects were observed in a 2

- generation rat reproduction toxicity study up to the limit dose. Because the highest dose tested was lower than the highest screening

- level EEC, the assessment says “risk cannot be precluded” and it does not reach a “no

- effect” finding for listed mammals. However, because no effects were observed in the reproductive toxicity test, and off

- site exposure via spray drift is not anticipated, the Agency is not at this time requiring further ecological risk mitigation me asures for mammals.

Finally, a s noted in the 2014 human health risk assessment for daminozide , the daminozide restricted entry interval (REI) specified on the registered labels of 24 hours is based on a dislodgeable foliar residue (DFR) study. To reflec t that there is no longer a non

- cancer dermal toxicological endpoint of concern, the REI may be lowered to 12 hours based on the current acute toxicity of the active ingredient. Any changes to the REI must be processed through the Registration Division.

B. Endangered Species

As noted above in Section III

. D

. , this Interim Registration Review Decision for daminozide does not contain a comple te ESA analysis. However, the A gency has completed a partial ESA analysis and is making a “ no effect ” determination under the ESA for direct and indirect adverse effects to listed species of fish, aquatic

- phase amphibians (that do not have terrestrial

- phases), aquatic invertebrates, aquatic plants, terrestrial invertebrates, monocots (in terrestrial and

w etland habitats), and dicots (in terrestrial and wetland habitats) that do not rely upon birds, terrestrial

- phase amphibians, reptiles, and/or mammals (for food or shelter) , and their designated critical habitat. See the Preliminary Ecological Risk Assess ment for the Registration Review of Daminozide and Daminozide (Alar ) for additional details on this determination.15 

### V. NEXT STEPS

A Federal Register Notice will announce the availability of this Interim Registration Review Decision . The Interim Decision will be publish ed in the daminozide registration review docket (EPA

- HQ

- OPP

- 2009

- 0242). As indicated above, this Interim Registration Review Decision for daminozide concludes that no additional data are required at this time and tha t lowering the 24 hour REI on current labels to 12 hours can be done voluntarily by non

- PRIA amendment. A final decision on the daminozide registration review case will occur after EDSP FFDCA section 408(p), complete pollinator, and ESA determinations ha ve been made.