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Hydrogen Cyanamide Proposed 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 and Characterization.........................................................................7

Dietary Assessment ..................................................................................................................7

Residential Assessment ............................................................................................................7

Cumulative Assessment............................................................................................................8

Occupational Assessment.........................................................................................................8

2. Human Incidents..........................................................................................................10

B. Ecological............................................................................................................................10

1. Risk Conclusions and Characterization.......................................................................11

Terrestrial Assessment...........................................................................................................11

Mammals................................................................................................................................11

Birds.......................................................................................................................................11

Plants......................................................................................................................................12

Aquatic Assessment................................................................................................................12

Fish and Invertebrates............................................................................................................12

Plants......................................................................................................................................13

2. Pollinator Studies and Assessment..............................................................................13

3. Ecological Incidents ....................................................................................................14

C. Benefits.................................................................................................................................14

D. Endangered Species Assessment ..........................................................................................15

E. Endocrine Disruptor Screening Program...............................................................................16

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION ....................................17

A. Risk Mitigation and Regulatory Rationale......................................................................17

B. Endangered Species.........................................................................................................18

C. Proposed Interim Registration Review Decision ............................................................18

V. NEXT STEPS AND TIMELINE...........................................................................................18

A. Interim Registration Review Decision ............................................................................18

B. Implementation of Mitigation Measures.........................................................................18
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Appendix A: Hydrogen Cyanamide (PC Code 014002) Label Table ............................................1

References:

This Preliminary Interim Decsion summarizes the Environmental Protection Agency's current 

position based on the following documents:

1. Registration Review – Ecological Risk, Environmental Fate, and Endangered Species 

Assessments for Hydrogen Cyanamide Riley, E., and I. Abdel-Saheb. February 27, 2014.

2. Hydrogen Cyanamide: Preliminary Risk Assessment for Registration Review. Khasawinah, 

A., J. Kidwell., and I. Nieves. March 12, 2014.

3. Hydrogen Cyanamide – Factors Affecting Hydrogen Cyanamide Risk Assessment: 

Response to Draft Risk Assessment for Registration Review. Khasawinah, A., J. Kidwell., 

and I. Nieves. July 14, 2015.

4. Cyanamide: Tier I Update Review of Human Incidents/Epidemiology for Draft Risk 

Assessment. Recore, S. and E. Evans. April 21, 2015.

5. Qualitative Assessment of the Benefits of Hydrogen Cyanamide (014002). Ratnayake, S., 

and S. Smearman. August 18, 2015. 

These and other supporting documents for the hydrogen cyanamide registration review case may 

be found in the docket EPA-HQ-OPP-2007-1014 at http://www.regulations.gov.
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I. INTRODUCTION

This document is the Environmental Protection Agency’s (EPA or the Agency) Proposed Interim 

Registration Review Decision for hydrogen cyanamide, hereafter referred to as cyanamide (case 

7005, PC 014002) 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 data or 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 cyanamide, additional documents 

can be found in EPA’s public docket (EPA-HQ-OPP-2007-1014) 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 as www.epa.gov/oppsrrd1/registration_review/.

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.

Cyanamide is a plant growth regulator (PGR) registered for use to promote uniform bud break in 

fruit trees and vines. It is registered for use on bearing fruit trees and vines before bud break, and 

is not registered for residential use. Cyanamide was first registered in 1984 and was not subject 

to reregistration.

Pursuant to 40 CFR section 155.50, EPA formally initiated registration review for cyanamide

(case 7005). The following summary highlights significant events that have occurred during the 

registration review of cyanamide and can be found in EPA’s public docket, EPA-HQ-OPP-2007-

1014, accessed at www.regulations.gov:

• March 18, 2008 – Publication of cyanamide 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.

• May 14, 2008 - Final Work Plan (FWP) for cyanamide was issued -- one public comment 

was received during the 60-day comment period for the cyanamide PWP; however, this 
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comment did not change the risk assessment or data needs identified in the PWP. 

Therefore, the FWP did not modify the PWP

• January 6, 2010 – Generic Data Call-In (GDCI) for cyanamide was issued.

• March 28, 2014 – The Agency published the Preliminary/Draft Ecological Risk 

Assessment for the Registration Review of Cyanamide and the Registration Review 

Preliminary/Draft Human Health Risk Assessment for Cyanamide for a 60-day public 

comment period. Two comments were received during the comment period

o Following the 60-day comment period, one of the cyanamide registrants, 

AlzChem, submitted a document requesting additional consideration of key 

factors in the Agency’s risk assessment. 

o A more detailed summary of these comments is included in the discussion of 

human health risk in Section III A I of this document.

• September 2015 – The Agency is now publishing the Hydrogen Cyanamide Proposed 

Interim Registration Review Decision, in docket number EPA-HQ-OPP-2007-1014 for a 

60-day public comment period. 

A. Public Comments

Two public comments were received during the 60-day comment period for the 

Preliminary/Draft Ecological Risk Assessment for the Registration Review of Cyanamide and the

Registration Review Preliminary/Draft Human Health Risk Assessment for Cyanamide. An 

anonymous public comment was received, but was not directly related to the cyanamide 

registration review case or related risk assessments. The Center for Biological Diversity (CBD) 

provided comments regarding the EPA’s obligations under the Endangered Species Act (ESA) 

for the registration review of cyanamide (EPA-HQ-OPP-2007-1014-0014). 

The Agency appreciates the comment from CBD. The EPA, along with the Services and the 

USDA, 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 Proposed Interim Decision for cyanamide does not 

contain a complete ESA analysis that includes effects determinations for specific listed species 

or designated critical habitat, but does include a screening-level assessment for all taxa of nontarget wildlife and plants. 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 cyanamide as part of 

completing this registration review. For additional information on this effort, please refer to 

section IIID of this document.
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II. USE AND USAGE

Cyanamide is a PGR and it is mainly used to induce a uniform bud break in fruits and berries in 

areas of the country where winter temperatures are not cold enough to induce it naturally. It is 

the only registered PGR available to induce uniform bud break in U.S. fruit production. Uneven 

bud break can significantly reduce fruit production, and lead to a lack of uniformity in fruit 

development, which hampers production practices, including pest management and harvest.

There are three Section 3 registrations, and all are end-use products formulated as soluble 

concentrates applied by airblast and groundspray.

Data on the use of PGRs in fruit and berry production is limited. According to available data, the 

top three use sites of hydrogen cyanamide, by amount of chemical used, are: grapes, cherries, 

and kiwifruit grown in California.1 Other sites with use include apples, blueberries, peaches and 

plums. Apples, blueberries, cherries, grapes, and kiwifruit had consistent usage of cyanamide 

from year to year over the 2004 to 2012 time period. Nearly 30% of the kiwifruit crop grown in 

California is treated annually, with 20,000 pounds (lbs) of active ingredient (AI) being used per 

year on average. Grapes and cherries are treated annually with 100,000 lbs AI each on average, 

which is equivalent to 5% of the grape and cherry crops grown in California. 

Additional information on use and usage of cyanamide is included in the Hydrogen Cyanamide 

Screening-Level Usage Analysis (SLUA) and Qualitative Assessment of the Benefits of Hydrogen 

Cyanamide (014002), both of which are available in the public docket EPA-HQ-OPP-2007-

1014, which can be accessed at http://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 cyanamide. For a detailed 

discussion of the human health assessment for cyanamide, see Hydrogen Cyanamide: 

Preliminary Risk Assessment for Registration Review and Hydrogen Cyanamide – Factors 

Affecting Hydrogen Cyanamide Risk Assessment: Response to Draft Risk Assessment for 

Registration Review available in the public docket EPA-HQ-OPP-2007-1014, which can be 

accessed at http://www.regulations.gov/.

 1 The data time period was 2004-2012. Data sources include California Department of Pesticide Regulation (CDPR); USDA 

NASS and EPA proprietary private market research.
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1. Risk Conclusions and Characterization

Dietary Assessment

Cyanamide is considered a non-food/non-feed use pesticide given its use as a PGR applied to 

fruiting trees and vines before budbreak. Therefore, the dietary risk assessment accounts for 

exposure through drinking water only. The acute probabilistic dietary assessment for cyanamide 

in drinking water results in an estimated risk of ≤110% of the acute reference dose (aRfD) at the 

99.9th percentile of exposure, 13% of the aRfD at the 99th percentile, and <1% of the aRfD at the 

95th percentile for all population subgroups. The chronic dietary exposure from hydrogen 

cyanamide in drinking water results in the estimated risk of ≤9.1% of the chronic reference dose. 

As cyanamide has been classified as as a Group C chemical, a possible human carcinogen, a 

cancer dietary risk assessment was also conducted. The cancer risk from cyanamide in drinking 

water is 9.32 x 10-7. 

Acute dietary risk is not of concern at the 99th percentile, which the Agency believes is the 

appropriate regulatory threshold for cyanamide. The dietary assessment includes drinking water 

only, and a probabilistic assessment was used to estimate ground and surface water 

concentrations In general, while drinking water can be refined to be included in probabilistic 

evaluations, there is more uncertainty around these estimates as compared to the utilization of 

monitoring data. Monitoring data are not available for cyanamide. In addition, for surface water 

assessments, the model used for Tier 2 drinking water assessments (PRZM-EXAMS) can

account for the reduction of exposure from a buffer zone associated with spray drift but not runoff. Given the 900-foot buffer for aquatic areas currently on cyanamide labels, the 99.9th

percentile is an overly conservative regulatory threshold for this particular case. Chronic and 

cancer dietary risk is not of concern for cyanamide at the 99.9th percentile.

Residential Assessment

There are no residential uses of cyanamide, so residential exposure is not expected. A residential 

risk assessment was not conducted, and residential risk is not expected.

Aggregate Assessment

An aggregate risk assessment takes single-chemical exposure into account from multiple 

pathways: food, drinking water, and residential exposure. Drinking water is the only anticipated 

route of dietary exposure for cyanamide since it is considered a non-food/non-feed use pesticide. 

Since there are no residential uses of cyanamide, an aggregate risk assessment was not 

conducted, and aggregate risk is not of concern. 

Spray Drift

Off-site movement of pesticides (spray drift) was incorporated into the risk assessment by 

assessing exposures for children (1 to <2 years old) and adults who have contact with turf where 

residues are assumed to have deposited. Dermal and incidental oral risk estimates were 

combined because the toxicity endpoint for each route of exposure is the same. The total 

applicable level of concern is 1000 and estimates yielded MOEs < 1000 for many of the 

groundboom and all of the airblast scenarios.
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Following publication of the human health risk assessment, one of the cyanamide registrants 

(AlzChem) provided additional considerations for refinement of the cyanamide risk estimates. 

The Agency considered the registrant’s submission, and made the following determination that 

resulted in revised estimates for spray drift:

• The dermal absorpotion factor (DAF) used in the calculation of occupational risk 

should be reduced from 11% to 2.84% based on revised selection of the most 

appropriate dose for determination of the DAF (from 800 μg/cm2 to 80 μg/cm2

respectively).

With the revised DAF, fewer MOEs < 1000 for the groundboom and airblast scenarios were

estimated than in the previous calculations. Labels currently recommend coarse spray for 

groundboom applications, and these scenarios present less risk concerns than for fine spray 

nozzles. The maximum distance for which the MOEs are below the LOC for these scenaros is 

200 feet. The type of foliage present during the application also bears on the risk estimates for 

drift for airblast scenarios; more drift is expected when there is less foliage. Since cyanamide is 

applied prior to budbreak, the Agency expects that only sparse foliage and vineyard scenarios 

would be relevant for this chemical. The maximum distance for which the MOEs are below the 

LOC for these scenarios is 125 feet (e.g., 17.6 lbs ai/A (maximum rate) applications to apples, 

cherries, or figs).

Cumulative Assessment

The Agency has not made a common mechanism of toxicity finding as to cyanamide and any 

other substances and this chemical does not appear to produce a toxic metabolite produced by 

other substances. The Agency has not assumed that it has a common mechanism of toxicity with 

other substances for the purpose of the registration review risk assessment, and cyanamide has 

not been included in a cumulative risk assessment. 

Occupational Assessment

Occupational Application Exposure and Risk

In the March 2014 cyanamide human health risk assessment, a No Observed Adverse Effects 

Level (NOAEL) of 2.0 mg/kg/day was selected as the point of departure (POD) for both dermal 

and inhalation routes of exposure, for short- and intermeditate-term exposure scenarios. As this 

chemical may only be used once per season, long-term exposure is not anticipated. The target 

Level of Concern (LOC) of 1000 is based on a 10X for intraspecies variation, 10X for 

interspecies extrapolation and a 10X database uncertainty factor (for the lack of acute and 

subchronic neurotoxicity, 28-day inhalation, subchronic dermal, and immunotoxicity studies). 

Based on the anticipated use patterns and current labeling, and types of equipment and 

techniques that can potentially be used, a range of occupational handler exposure scenarios were 

assessed. All scenarios presented risk estimates of concern (MOEs < 1000). 

As indicated previously in the discussion of spray drift, one of the cyanamide registrants 

provided additional considerations for refinement of the cyanamide risk assessment following 

the 60-day comment period on the draft risk assessments. The Agency considered the 
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registrant’s submission, and made the following determinations that resulted in revised risk 

estimates:

• The dermal absorpotion factor (DAF) used in the calculation of occupational risk 

should be reduced from 11% to 2.84% based on revised selection of the most 

appropriate dose for determination of the DAF (from 800 μg/cm2 to 80 μg/cm2

respectively).

• The point-of departure (POD) for assessing risks from short- and intermediate-term 

exposures should be revised to the NOAEL at 5 mg/kg/day from the maternal toxicity 

in the rat development study rather than the subchronic/chronic dog study (2.0 

mg/kg/day).

While the majority of the airblast scenarios still do not reach the LOC of 1000 for the dermal 

route of exposure (i.e., single layer, no gloves; double layer gloves), all scenarios exceed the 

LOC for both dermal and inhalation for the engineering controls scenarios (closed mixing 

loading systems for mixers/loaders, and enclosed cabs for applicators).

Occupational Cancer Exposure and Risk

As cyanamide is classified as a Group C chemical, a possible human carcinogen, a Q1* of 6.64 x 

10-2 (mg/kg/day)-1 has been calculated for this chemical, and an occupational cancer assessment 

was conducted. Estimated occupational handler cancer risks for airblast and groundboom 

equipment ranged from 1.4x10-6 to 1.7x10-4

. The range of values represent scenarios from 

baseline personal protective equipment (PPE = single layer, no gloves) to more protective 

engineering controls (i.e., closed cabs) for both exposure routes (dermal and inhalation), from the 

lowest application rate (6.6 lb ai/A) to the highest application rate (17.6 lb ai/A), assuming the 

same applicator applying cyanamide over a 35-year career and a 78-year lifespan at 10 

applications per year. The cancer risk estimate for scenarios with closed mixing/loading systems 

range from 7.3 x10-6 to 1.4x10-6 ; enclosed cabs range from 1.7x10-6 to 6.4x10-5. 

Comparison of Risk Estimates Using Standard Assumptions Versus Passive Dosimetry and 

Biomonitoring Data

The Agency previously completed an assessment comparing passive dosimetry and 

biomonitoring data against the Agency’s default assumptions found in the Pesticide Handler 

Exposure Database (PHED) following a registrant requested label change. The result of this 

comparison showed that the overall exposures to handlers were still of concern for most 

scenarios. For the purposes of registration review, the Agency updated this assessment to reflect 

current assumptions and default values. 

Risks were identified for nearly all scenarios for applicators without engineering controls for 

both dermal and inhalation pathways (MOEs <1000). Using engineering controls (i.e., closed 

cab), passive dosimetry data resulted in risk estimates of concern via the dermal route of 

exposure, and no risk estimates of concern via the inhalation route of exposure, except for one 

scenario (i.e., applicator using 17.6 lb ai/A over 40 acres of crop). All scenarios assessed with 

the biomonitoring data resulted in risk estimates of concern except for one scenario (applying at 

the 6.6 lb ai/A to 20 acres). 
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Cancer risk estimates using the passive dosimetry for closed cab airblast equipment ranged from 

2x10-6 to 5x10-6, and for open cab with coveralls resulted in cancer risk estimates that ranged from 

1.4x10- 5 to 7.6x10-5

. Exposure data from the biomonitoring studies resulted in cancer risk 

estimates ranging from 1.4x10-6 to 2.8x10-5 for applicators using chemical-resistant suits.

Occupational Post-Application Exposure and Risk

Quantitative post-application assessments were not peformed. There are potential sources of 

post-application inhalation and dermal exposure to individuals performing postapplication 

activities in previously treated fields (e.g., volatilization of pesticides and resuspension of dusts 

and/or particulates that contain pesticides). However, the Agency does not expect significant 

post-application risk due to the expectation of low exposure. At the time of application, crops 

are in a state of dormancy where plants exhibit little or no foliage growth, and the only likely 

post-application activity, pruning, must be completed before cyanamide application per the 

product labels. According to the Worker Protection Standard guidelines the minimum REI for 

cyanamide should be 24 hours based on cyanamide’s acute toxicity profile (category II), 

therefore, the 72-hour REI on the registered labels is protective.

2. Human Incidents

EPA reviewed the Incident Data System (IDS) and the SENSOR-Pesticides database. IDS

includes reports of alleged human health incidents from various sources, including mandatory 

Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports from 

registrants, other federal and state health and environmental agencies, and individual consumers. 

From January 1, 2008 to April 2, 2015, there were no incidents reported involving cyanamide. 

The SENSOR-Pesticides database covers 12 states from 1998-2011, and for this period, a total of 

four cases were identified. All four cases were work-related; three cases were agricultural 

workers including two fieldworkers and one handler who became ill while making the pesticide 

application. All were low in severity.

Based on the low frequency and low severity of incident cases reported for cyanamide in both 

databases, there does not appear to be a concern at this time.

3. Tolerances

Currently registered uses are considered non-food/non-feed uses and no tolerances have been 

established for residues of hydrogen cyanamide. No Codex, Canadian, or Mexican maximum 

residue levels (MRLs) have been established for hydrogen cyanamide.

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 cyanamide. For a detailed 

discussion of the ecological assessment for cyanamide, see Registration Review – Ecological 

Risk, Environmental Fate, and Endangered Species Assessments for Hydrogen Cyanamide dated 
11

February 2014, vailable in the public docket EPA-HQ-OPP-2007-1014, which can be accessed at

http://www.regulations.gov/. 

The Agency also completed a preliminary endangered and threatened (listed) species assessment 

for cyanamide and identified potential risks to terrestrial and semi-aquatic plants, mammals, 

birds and reptiles. 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 cyanamide. 

1. Risk Conclusions and Characterization

Terrestrial Assessment

Mammals

Acute and chronic risk was assessed for all uses of cyanamide for mammals, and risk estimates 

exceeded the Agency’s LOC for most scenarios. The application rate as an input to the Agency’s 

terrestrial model (T-REX) was a major factor in the estimation of risk in the assessment (using 

the maximum labeled rate of 17.6 lbs ai/A). While there are acute-dose based exceedances of the 

risk quotient (RQ), the models indicate greater potential chronic risks concern. The magnitude of 

the acute RQs indicates that potential risk would not extend far beyond the treated field itself.

The vapor pressure of cyanamide is such that it is likely to volatilize while in the air, or from dry 

surfaces, such as a plant. Other environmental fate data such as the aerobic soil metabolism 

study also indicate a half-life of less than a day, suggesting that the foliar dissipation half-life for 

hydrogen cyanamide is less than the 35 days assumed in T-REX. The use of the default value of 

35 days may lead to an overly conservative risk estimate as without prolonged esposure, chronic 

risks to mammals may be considerably reduced.

In addition, since cyanamide is only applied in orchards, once per year, typically between 

December and March, this limited geographic and temporal limitation of hydrogen cyanamide 

use poses an uncertainty in the extent of both acute and chronic exposure. It is also possible that 

given the timing of application, and the quick degradation of cyanamide, that exposure may not 

occur duing the mating season of many mammals, reducing the likelihood of reproductive effects 

seen in chronic toxicity studies.

Birds

Acute and chronic risk was assessed for all uses of cyanamide for birds, and risk estimates 

exceeded the Agency’s LOC for most scenarios. As indicated ealier for mammals, the 

application rate was major driver in the risk estimates calculated. 

Acute dietary endpoint for birds is non-definitive (>5000 ppm; no mortality was identified in any 

of the avian studies).. This valuewas used to calculate an upper bound for potential risk, and 

while acute risk to birds remains an uncertainty, the potential for acute-dose based exceedances 
12

of the RQ were identified. The Agency’s calculations based on the terrestrial model T-REX 

indicated greater potential chronic risks of concern. However, as suggested above with regard to 

mammals, available data for cyanamide indicate that this chemical degrades rapidly in the 

environment. Without prolonged exposure, chronic risks to birds may be considerably reduced, 

and since there is a geographic and temporal limitation of hydrogen cyanamide use, these factors 

further reduce the extent of potential exposure.

Terrestrial Invertebrates

The acute honeybee acute contact toxicity study did not yield a definitive toxicity 

endpoint.While the available data demonstrate that cyanamide is essentially non-toxic to the 

honey bee, the high application rates used may pose risks to bees as a result of high field 

residues. Additional pollinator data would reduce uncertainties associated with risks to 

beneficial insects.

Terrestrial Plants

Hydrogen cyanamide is a plant growth regulator, and as expected it has the potential to affect 

non-target plants. Risk quotients based on seedling emergence studies indicate that cyanamide 

can pose a risk to non-target plants in adjacent fields through drift and runoff. However, because 

effects to seedling emergence were seen at the lowest exposure tested for the most sensitive 

species (lettuce), it is not clear how low an exposure might elicit adverse effects of concern.In 

addition, because there is a 900-foot buffer from water bodies risk from exposure to semi-aquatic 

plants through runoff remains an uncertainty since the Agency’s terrestrial plant model 

(TerrPlant) cannot account for the effect of a buffer zone.

The Agency was able to refine potential exposure of plants to cyanamide from drift off of the 

field. Based on this analysis, airblast applications for the orchard uses and ground spray for the 

other uses limit the potential for exposure from drift such that most of the assessed species would 

not be expected to be at risk beyond the edge of the field. As indicated in the Ecological Incident 

section below, though, non-target plants away from the field could be impacted if applications 

occur under conditions that strongly favor spray drift.

Aquatic Assessment

Fish and Invertebrates

Acute risk estimates are below the Agency’s levels of concern for all modeled scenarios for both 

fish and aquatic invertebrates. Chronic risk estimates were not calculated due to a non-definitive 

endpoint for freshwater fish, and inability to calculate an acute-to-chronic ratio (ACR) for 

estuarine-marine fish given the non-definitive endpoint for freshwater fish. Chronic risk is

expected to be low for freshwater invertebrates. An ACR was applied for marine/estuarine 

invertebrates, and risk estimates indicate chronic risks to crustaseans are not likely, but cannot be 

precluded for mollusks. However, the Agency’s current aquatic models (PRZM/EXAMS) 

cannot account for the impact of the 900ft buffer from water bodies that already exists on labels. 
13

Since the estimated environmental concentrations (EECs) that are used to calculate risk estimates 

are in-part, driven by the modeled run-off, risk may be overestimated.

Aquatic Plants

Risk estimates are below the Agency’s levels of concern for all modeled scenarios for aquatic 

plants. As discussed previously EECs are primarily driven by the modeled run-off, which 

assumes no buffer between the site of application and the water body, so these risk estimates 

may also be overestimated.

2. Pollinator Studies and Assessment

When initially scoping the registration review for cyanamide, 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 Bees2, 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 make a final registration review decision, EPA intends to issue a 

DCI to obtain these data. In the near future, EPA will provide additional information and 

guidance on this effort. The pollinator studies that could be required are included in Table 1 

below. The required data will inform the pollinator risk assessment.

Table 1. Proposed Pollinator Data Requirements

Guideline # Study

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)

 2 http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf
14

**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.

3. Ecological Incidents

A review of the Ecological Incident InformationSystem (EIIS) database for incidents involving 

hydrogen cyanamide was conducted on for this registration review. Two incidents for hydrogen 

cyanamide are reported in the database. The first incident resulted from an accidental misuse of 

cyanamide on grape vineyards. The incident report indicates that hydrogen cyanamide applied 

during stormy weather using a high pressure sprayer resulted in defoliation of several groves of 

nearby lemon trees. Label language requires use of a low pressure sprayer and application only 

when weather conditions do not favor drift. In the second incident, the California Department of 

Pesticide Regulations reported 380 acres of kiwifruits were damaged after cyanamide 

application. No reported cyanamide incidents were found in the Avian Incident Monitoring 

System (AIMS).

Reported incidents are consistent with the Agency’s risk assessment which indicates that direct 

effects to terrestrial plant species are expected from the currently registered use of this pesticide.

C. Benefits

Given the possible ecological risks identified in the ecological risk assessment, the Agency 

considered the benefits of cyanamide, consistent with its regulatory authority under FIFRA. The 

economic benefits of using cyanamide are significant in fruit-producing areas where the critical 

number of chilling hours needed for bud break does not occur or is not consistent. As noted in 

Section II of this document, uneven bud break can significantly reduce fruit production and lead 

to a lack of uniformity in fruit development, which hampers production practices, including pest 

management and harvest.

Growers can incur substantial yield losses if minimum chilling hours do not occur. For example, 

a yield loss of up to 25% could occur if Alabama peach growers producing the Ruston Red 

variety do not receive the minimum number of chilling days, which would be a significant 

economic loss. With up to 30% of the kiwi crop treated annually with hydrogen cyanamide, it 

can be considered a critical use for kiwi growers in California. For fruit crops with a much 

larger number of acres in production nationally than kiwi, such as cherries and grapes, yield and 

quality losses on these crops can also result in significant gross revenue impacts for growers. 

Fertilizer-based compounds such as calcium ammonium nitrate have been recognized in the 

literature, and by agricultural extensions, as potential tools for enhancing bud break. However

they are not registered as plant growth regulators in the U.S and have been found less effective 

for this purpose as compared to cyanamide. Cyanamide is the only registered plant growth 

regulator available to induce uniform bud break in U.S. fruit production. 

For a detailed discussion of the benefits identified for cyanamide, see Qualitative Assessment of 

the Benefits of Hydrogen Cyanamide (014002), available in the public docket EPA-HQ-OPP2007-1014, which can be accessed at http://www.regulations.gov/. 
15

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 report3 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 

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”4

, 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 Proposed Interim 

Decision for cyanamide 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 cyanamide. 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 Proposed 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 cyanamide as part of completing this registration review.

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

4 http://www.epa.gov/espp/2013/nas.html
16

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 cyanamide, 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), cyanamide is

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

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

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

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

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

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

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

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20135

 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.6

 

In this proposed interim decision, EPA is making no human health or environmental safety 

findings associated with the EDSP screening of cyanamide. Before completing this Registration 

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

 5 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

6 http://www.epa.gov/endo/
17

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION

A. Risk Mitigation and Regulatory Rationale

As discussed in Section III, there are occupational risks of concern for cyanamide. However, 

they are mitigated through label requirements which require closed systems for mixing and 

loading, and enclosed cabs for application. While these requirements are currently on each of 

the three end-use labels, the handgun application are proposed to be removed from labels. In 

addition, current personal protective equipment language on the cyanamide labels are proposed 

to be updated because the use of chemical-resistant suits by applicators while in an enclosed cab 

is inconsistent with federal regulations (40 CFR Section 170.240 d.5.iv). 

Bystander risks from spray drift were identified for cyanamide. The calculations for spray drift 

(incorporating the revised DAF) indicate buffers are appropriate tools to mitigate risk concerns. 

As the current cyanamide labels include a restriction that prohibits persons not involved in the 

application/mixing/loading of cyanamide within 100 yards (300 feet) of the application area, this 

mitigation is sufficiently protective of estimated bystander risk.

 

The Agency proposes that labels require that nozzles that produce a coarse droplet spectrum are 

to be used for groundboom applications, rather than “recommended” as worded currently on enduse product labels, as risks associated with drift were identified for applications using fine and 

medium droplet size.

Appendix A of this document summarizes these label actions taken for cyanamide. Appendix B

of this document outlines the amended labeling language. The EPA has discussed the proposed 

mitigation with each of the cyanamide registrants.

As is appropriate under FIFRA, the Agency considered the benefits of cyanamide with the risks 

of use, use in making it’s determination. As discussed in Section IIIC of this document, 

cyanamide is the only registered plant growth regulator available to induce uniform bud break in 

U.S. fruit production, and economic benefits of using cyanamide are significant in fruit 

producing areas where the critical number of chilling hours needed for bud break does not occur 

or is not consistent. 

While ecological risks of concern were identified, additional mitigation is not being proposed at 

this time. The Agency believes that the extent to which ecological risk mitigation (e.g., 900-foot 

buffer for aquatic areas, spray drift language) is already on current labels, and due to the limited 

temporal and geographic use of this chemical, there are appropriate measures currently in place 

to mitigate some of the ecological risks associated with the use of cyanamide. Additionally, the 

proposed requirement of coarse droplet nozzles will limit drift, and further reduce risk. 
18

B. Endangered Species

As noted above in Section IIID , this Proposed Interim Registration Review Decision for 

cyanamide does not contain a complete ESA analysis. A screening level risk assessment was 

completed for cyanamide, and risk is identified as possible for listed, non-target species. Given 

the possibility of risk to some listed terrestrial terrestrial plants, mammals, birds, and reptiles, the 

Agency is not able to make an endangered species determination. Several uncertainties remain 

regarding potential exposure of these species to cyanamide including the impact of the 900-foot 

vegetative buffer strip on reducing runoff, and the impact of cyanamide application timing and 

geographic limitations on exposure to listed species. To address these uncertainties, further 

refinement of Agency models to account for the impact of vegetative buffers is needed. In 

addition, the life history of listed species must be further evaluated in order to determine whether 

terrestrial plants, mammals, birds, and reptiles co-occur with cyanamide use sites.

C. Proposed Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed 

Interim Registration Review Decision. Except for the EDSP and ESA components of this case, 

the Agency has made the following Proposed Interim Registration Review Decision: (1) no 

additional data are required at this time; and (2) changes to the affected registrations and their 

labeling are being proposed.

In this proposed interim registration review decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of cyanamide, nor is it 

making a complete endangered species finding. The Agency’s final registration review decision 

for cyanamide will depend upon both the result of an ESA Section 7 consultation with the 

Services, and an EDSP FFDCA section 408(p) determination.

V. NEXT STEPS AND TIMELINE

A. Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed 

Interim Registration Review Decision, and placing it in the cyanamide registration review docket 

(EPA-HQ-OPP-2007-1014) for public comment for 60 days. A Federal Register Notice will 

announce the availability of this Proposed Interim Registration Review Decision for Hydrogen 

Cyanamide and initiate a 60-day comment period. If there are no significant comments or 

additional information submitted to the docket during the comment period that leads the Agency 

to change its proposed decision, EPA will issue an Interim Registration Review Decision for 

Hydrogen Cyanamide (case 7004). 

B. Implementation of Mitigation Measures
19

Once the Interim Registration Review Decision is issued in final form, registrants are to submit 

amended labels that include the label changes summarized in Appendix A to the Agency for 

approval within 60 days following issuance of the Interim Registration Review Decision in final 

form. 
20

 7 Standard developed by the American Society of Agricultural and Biological Engineers. See 

http://cdn2.hubspot.net/hub/95784/file-32015844-

pdf/docs/asabe_s572.1_droplet_size_classification.pdf.

Appendix A: Summary of Proposed Actions for Hydrogen Cyanamide

Registration Review Case#: 7005

PC Code: 014002

Chemical Type: Plant Growth Regulator

Chemical Family: Not applicable

Mode of Action: Not determined

Affected 

Population(s)

Source of 

Exposure

Route of 

Exposure

Duration of 

Exposure

Toxicological Endpoint used for Risk 

Assessment

Action(s) Taken

Occupational 

application

workers

Air

Equipment

Dermal

Inhalation

Short-term

Intermediate-term

MRID 41288806. Maternal toxicity 

in the rat developmental

study: decreased body weight gain, 

decreased food consumption and

hypoactivity in one third of the 

treated animals.

Handgun application 

use must be removed 

from labels and 

prohibited

Clarify PPE that are to 

be worn while 

mixing/loading and 

applying, and what 

PPE must be 

available for 

emergencies.

Bystanders Drift (Turf) Dermal

Incidental Oral

Short-term MRIDs 41288802 & 41390501

Chronic Dog: NOAEL= 1 mg/kg/day.

LOAEL = 5 mg/kg/day from the 

chronic dog based on increased 

incidences of rough haircoat, 

desquamation of the skin, tremors, 

and salivation; decreased body 

weight gain; decreased T4 in males;

increased relative thyroidparathyroid weights brown 

pigment in liver Kupffer cells; 

thymic atrophy; testicular

inflammation; and 

aspermatogenesis, and

hypospermatogenesis.

Nozzles that product 

a Coarse droplet 

spectrum, as defined 

by the ASABE S572.17

are required
Docket Number EPA-HQ-OPP-2007-1014

www.regulations.gov

Appendix B: Hydrogen Cyanamide (PC Code 014002) Label Table

Summary of Proposed Labeling Changes for Hydrogen Cyanamide Uses

Description Proposed Labeling Language for Hydrogen Cyanamide Use Products Placement on Label

End Use Products

Spray Drift Management

(changes to specify 

coarse droplet size only)

“Avoid spraying under conditions of a temperature inversion when drift hazard is increased. Coarse 

sprays must be used in PRODUCT NAME applications. Do use nozzles or nozzle configurations which 

generate fine spray droplets. Do not increase spray volume by increasing nozzle pressure because this 

will the number of fine droplets in the spray. It is important to understand the the responsibility for 

control of spray drift is with the persons making the use recommendation, the applicator, and the 

grower.”

Directions for Use under Spray 

Drift Management

Replace the first paragraph under 

Spray Drift Management

Use Restriction (this 

removes the reference to

handgun use)

Remove the last two sentences starting/ending with “If handgun spray...through the tree.”

“Spray according to the anticipated budbreak timing of the earliest variety within an interplanted orchard, 

unless each variety can be sprayed separately without significant drift of overspray contacting previously 

sprayed varieties or nontarget varieties.”

Directions for Use under Crops

under Peaches/Nectarines

Revise the second paragraph 

under Peaches/Nectarines

Personal Protective 

Equipment Clarification

“Mixers and loaders using the required closed system must wear:

• long-sleeved shirt and long pants

• shoes plus socks

• chemical-resistant apron

• chemical-resistant gloves such as Barrier Laminate, or Butyl rubber ≥ 14 mils, or Nitrile Rubber 

≥ mils, or Neoprene Rubber ≥ 14 mils, or Polyvinyl Chloride (PVC) ≥ 14 mils, or Viton ≥ 14 

mils

• protective eyewear

All handlers cleaning equipment must wear:

• chemical-resistant gloves such as Barrier Laminate, or Butyl rubber ≥ 14 mils, or Nitrile Rubber 

≥ mils, or Neoprene Rubber ≥ 14 mils, or Polyvinyl Chloride (PVC) ≥ 14 mils, or Viton ≥ 14 

mils

• chemical resistant footwear plus socks

• protective eyewear

• chemical-resistant protective suit

• a NIOSH approved particulate resipirator with any N, R, or P filter, NIOSH approval number 

prefix TC-84A; or a NIOSH-approvedpowers air purifying respirator with an HE filter with 

NIOSH approval number prefix TC-21C.

Personal Protective Equipment

Replaces the current PPE list
2

Applicators using the required enclosed cabs must wear:

• long-sleeved shirt and long pants

• shoes plus socks

• a NIOSH approved particulate resipirator with any N, R, or P filter, NIOSH approval number 

prefix TC-84A; or a NIOSH-approvedpowers air purifying respirator with an HE filter with 

NIOSH approval number prefix TC-21C.

Applicators using the required enclosed cabs must have the following equipment immediately available 

and stored in a chemical-resistant container, such as a plastic bag. The following must be worn if it is 

necessary to exit the cab and contact pesticide treated surfaces in the treated area, and must be removed 

and stored in a chemical-resistant containter before reentering the cab:

• Chemical-resistant protective suit

• chemical-resistant gloves such as Barrier Laminate, or Butyl rubber ≥ 14 mils, or Nitrile Rubber 

≥ mils, or Neoprene Rubber ≥ 14 mils, or Polyvinyl Chloride (PVC) ≥ 14 mils, or Viton ≥ 14 

mils

• chemical resistant footwear plus socks

• protective eyewear.”