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 ........................................................................................11

E. Endocrine Disruptor Screening Program.............................................................................12

IV. INTERIM REGISTRATION REVIEW DECISION..............................................................13

A. Risk Mitigation and Regulatory Rationale..........................................................................14

B. Endangered Species.............................................................................................................14

V. NEXT STEPS..........................................................................................................................15
3

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://www.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 appropriate, an Interim Registration Review Decision before completing a 

registration review. Among other things, the Interim Registration Review Decision may: 1)

require new risk mitigation measures; 2) impose interim risk mitigation measures; 3) identify 

additional 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 documents 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 that 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 practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the Agency periodically 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 whether 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 evaluated risks to 

threatened and endangered species, the Agency will complete its endangered species assessment 

and any necessary consultation with the Services for daminozide prior to completing the 

daminozide registration review. Likewise, the Agency will 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 necessary 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 

shorter and more densely packed. It is registered for use in nurseries, shadehouses, and 
5

greenhouses, applied as a foliage spray that is systemically distributed throughout the plant. 

Daminozide has no registered food uses. Additionally, there are no registered residential 

approved for daminozide. The Reregistration Eligibility Decision document (RED) for 

daminozide was completed 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 for 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-OPP2009-0242, accessed at www.regulations.gov.

• June 24, 2009 – Publication of daminozide Preliminary Work Plan (PWP) for a 60-day 

public comment period. The Preliminary Work Plan (PWP) was accompanied by the 

scoping document and problem formulation.

• December 3, 2009 – A Final Work Plan (FWP) for daminozide was issued. No public 

comments were received during the 60-day comment period for the daminozide PWP. 

Therefore, the FWP did not modify the PWP.

• September 22, 2010 – Generic Data Call-In (GDCI-035101-915) for daminozide was 

issued.

• December 24, 2014 – The Agency published 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 published the Daminozide Proposed Interim Registration 

Review Decision for a 60-day public comment period.

o EPA also published the following use/usage and benefits document regarding 

daminozide: Qualitative Assessment of Daminozide Use in Ornamental Plant 

Production (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 controlling the development of commercially grown 

container plants by changing their growth habit; usually by making a plant shorter and more 

densely packed. It is used in nurseries, shadehouses, and greenhouses, applied as a foliage spray 

that is systemically distributed throughout the plant. Daminozide has no registered food uses. 

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

accessible at 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 

quantitative risk assessment 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, which is 

available in 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.

Aggregate 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 Assessment
7

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. Daminozide 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 risk 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-application exposure is possible, 

the 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 potential 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 dermal 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 for 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 activities. 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 those 

with the highest cancer risk estimates, this use scenario is protective of cancer risk for 

daminozide uses applied via a backpack sprayer or manually-pressurized handwand.

All daminozide registrations approved for use on ornamental plants include label language 

advising different ranges for the concentration of mixed solution to use when applying 

daminozide to different species of plants. In certain cases, different application concentrations 

are also suggested for multiple uses types on the same target plant; for example, daminozide uses 

on cut versus potted chrysanthemums. Due to the wide range of application rates for 
8

daminozide, it is unlikely that applicators will be applying daminozide solely at the maximum 

single application rate for the full length of a theoretical 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, probable 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 products 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 exposure 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 

quantitative risk assessment in support of the registration review of daminozide. For a detailed 

discussion of the ecological assessment for daminozide see the Preliminary Ecological Risk 

Assessment for the Registration Review of Daminozide dated December 4, 2014, which is 

available in the public docket EPA-HQ-OPP-2009-0242 and is accessible via

http://www.regulations.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 wetland 
9

habitats), and dicots (in terrestrial and wetland habitats) that do not rely upon birds, terrestrialphase 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 Agency will complete its endangered species assessment for 

daminozide. At currently labeled rates, risk 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, direct 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 nontarget terrestrial animals, including birds, reptiles, terrestrial-phase amphibians and mammals.

Ecological risk findings for daminozide are summarized as follows:

Mammals

Definitive toxicity endpoints could not be determined for acute or chronic rat studies. Using dosebased intake 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 application rates on labels are 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 Plants

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 chronic toxicity of daminozide would have to 

be at least 8,600 times greater than the acute toxicity.

Terrestrial Invertebrates and Plants

Daminozide 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 from contact exposure to daminozide residues on plants is expected to be low. All calculated 
10

risk quotients for terrestrial plants 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 additional 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 final 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 Agency 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

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

NonGuideline** 

(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.pdf
11

3. Ecological 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 evaluated databases.

C. Benefits

Daminozide is a systemic plant growth regulator (PGR) registered for use in controlling the 

development of commercially grown container plants by changing their growth habit. 

Daminozide reduces the internode length of ornamental plants by inhibiting the synthesis of 

gibberellic acid, resulting in an ornamental plant that is shorter and more densely packed. 

Controlling plant size is an important aspect of greenhouse plant production. Reduction of 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 minimizes 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 may be desirable for young 

plant production, since the growth inhibition may not be desirable after transplanting. 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, 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 threatened (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 report1 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 Approaches 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 (SFIREG) meetings. The agencies also held stakeholder workshops in April 

and October 2014, allowing additional opportunities for stakeholders to comment on the Interim 

 1 http://www.nap.edu/catalog.php?record_id=18344
12

Approaches. Additional workshops are planned to enhance stakeholder involvement. As part 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 Interim 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 application 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 have 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 registration 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 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 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.html
13

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. A second list 

of chemicals identified for EDSP screening was published on June 14, 20133 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 

associated with the EDSP screening of daminozide. Before completing this Registration Review, 

the Agency will make an EDSP FFDCA section 408(p) determination.

IV. INTERIM REGISTRATION REVIEW 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 were 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://www.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 daminozide at this time. 

Current label language, such as the restriction of a 24-hour storage limit for tank mixes 

containing daminozide, is adequate to mitigate occupational risk from exposure to daminozide 

and its degradate, UDMH.

Daminozide does not raise significant concern for ecological risks. Daminozide is applied by a 

drench/foliar spray application method to ornamentals in nurseries, shadehouses, and 

greenhouses, a use pattern which greatly minimizes the potential for spray drift. Furthermore, 

daminozide is most efficacious when applied under still conditions, and it is the Agency’s 

understanding that it is a standard practice to time daminozide applications to take place under 

still, humid conditions, which further reduces the potential for spray drift. Finally, the two enduse product labels that allow for uses outside of enclosed greenhouses both restrict use in 

production areas not under cover to containerized ornamental plants, 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 measures for mammals.

Finally, as 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 reflect 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 complete ESA analysis. However, the Agency 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 

wetland 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 Assessment 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 published 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 that 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 have been made.