2 

### Hydrogen Cyanamide Proposed Interim Decision

- Table of Contents

**Contents**

I. INTRODUCTION

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

II. USE AND USAGE

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

III. S CIENTIFIC ASSESSMENTS

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

A. Human Health

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

1. Risk Conclusions and Characterization

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

................................ ................................ ................................ .................. 7

Residential Assessment

................................ ................................ ................................ ............ 7

Cumulative Assessment

................................ ................................ ................................ ............ 8
Occupati onal 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 I nvertebrates

................................ ................................ ................................ ............ 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. Pro posed Interim Registration Review Decision

................................ ............................ 18

V. NEXT STEPS AND TIMELINE

................................ ................................ ........................... 18

A. Interim Registration Review Decision

................................ ................................ ............ 18

B. Implementation of Mitigation Measures

................................ ................................ ......... 183 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. Februa ry 27, 2014

.

2. Hydrogen Cya namide: Prelimin ary Ri sk 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

.4 

### I. INTRODUCTION

This document is the Environmental Protection Agency’s (EPA or the Agency) Proposed Interim Registration Review Decision for hydrogen cyanamide, hereafter ref erred 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 F ederal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it determines it to be appropriate, a n I nterim R egistration
R eview D ecision before completing a registration review. Among other things, the I nterim
R egistration R eview D ecision may : 1) require new risk mitigation measures ; 2) impose interim risk mitigation measures ; 3) identify data or information required to complete the review ; and 4) include schedules for submitting the required data, conducting the new risk assessmen t 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 Fo od 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

unrea sonable 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 registe red 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 pe sticides 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_rev iew/

.

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.

C yanamide 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 P reliminary W ork P lan (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; how ever, this5 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. T wo comments were received during the commen t 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 c omments regarding the EPA’s obligations under the Endangered Species Act (ESA) for the reg istration 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 continui ng to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and th eir designated critical habitat. T he ecological risk assessment supporting this Proposed Interim Decision for cyanam ide does not contain a complete ESA analysis that includes effects determinations for specific listed species or designated critical habita t, but does include a screening

- level assessment for all taxa of non

target wildlife and plants . Once the agencies h ave fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses for cyanamide as part of completing this regis tration review. For additional information on this effort, please refer to
section IIID of this document.6 

### II

. USE AND USAGE

C yanamide 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 produ ction. 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

- us e 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

, a re: 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 t ime 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 i s 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
Scre ening

- 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

qua nti tative risk assessment in support of the registration review of cyanamide

. For a detailed
discussion of the human health assessment for cyanamide

, see Hydrogen Cya namide:
Prelimin ary Ri sk Assessment for Registration Review and Hydrogen Cyanamide

– Factors Affecting Hydrogen Cyanamide Risk Assessment: Response to Draft Risk Assessment for Registration Review available i n 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 D epartment of P esticide R egulation (CDPR); USDA

NASS and EPA proprietary private market research.7 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 a cute probabilistic dietar y assessment for cyanamide in drinking water results in an estimated risk of ≤110% of the acute reference dose (aRfD) at the
99.9 th percentile of exposure, 13% of the aRfD at the 99 th percentile, and <1% of the aRfD at the
95 th 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 99 th percentile , which the Agency believes is the appropriate regulatory threshold for cy anamid e. T he 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 run

off. Given the 900

- foot buffer for aquatic areas currently on cyanamide labels, the 99.9 th percentile is an overly conservative regulatory threshold for this particular case. Chronic and cancer dietary risk is not of concern for cyanamide at the 99.9 th percentile

.

Residential Assessment

There are no res idential 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, dri nking 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 yield ed MOEs < 1000 fo r many of the groundboom and all of the airblast scenarios.8 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% ba sed on revised selection of the most appropriate dose for determination of the DAF (from 800 μg/cm 2 to 80 μg/cm 2 respectively).

With the revised DAF, fewer MOEs < 1000 for the groundboom and airblast scenarios were estimated than in the previous calculations . Labels currently recommend co a rse 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 scena ros is
200 feet. The type of foliage present during the application also bears on the risk estimate s 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 vine yard 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).

Cumu lative 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 Appli cation 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 i ntermed itate

- 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 th at 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, o ne of the cyanamide registrants

pr ovided additional considerations for refinement of the cyanamide risk assessment following
the 60

- day comment period on the draft risk assessments. The Agency considered the9 registrant’s submission, and made the following determinations th at resulted in r evised risk
estim ates:

• 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/cm 2 to 80 μg/cm 2 respectively).

• The point

- of departure (P OD ) 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 eng ineering controls scenarios (closed mixing loading systems for mixers/loaders, and en closed cab s for applicators)

.

Occupational Cancer Exposure and Risk As cyanamide is classified as a Group C chemical, a possible human carcinogen, a Q 1 * of 6.64 x
10

- 2 (m g/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 highes t 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 t his 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 v ia 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 ris k estimates of concern except for one scenario (applying at the 6.6 lb ai/A to 20 acres).10 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 cance r 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 Exposu re and Risk Quantitative post

- application assessments were not peformed. T here 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)

. H owever, 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 dorman cy where plants exhibit little or no foliage growth, and the only likely post

- application activity, p r uning, 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
includ es reports of alleged human health incidents from various so urces, including mandatory
Federal I n sec ticide

, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports from registrants, other federal and sta t e health and environmen t al agencies, and individual consumers. From January 1

, 2008 to April 2, 2015, there were no incidents reported in volving cyanam ide.
The SENSOR

- Pesticides database covers 12 states from 1998

- 2011, and for this period, a total of
four cases were identified. Al l 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 t he 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 cyana mide. 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
qua nt itative 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 dated11 February 2014, vailable i n 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 Ag ency 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

a ssessments 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 r ate as an input to the Agency’s terrestrial model (T

- REX) was a major factor in the estimation of risk in the assessment (usi ng 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 exte nd 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 d ata such as the aerobic soil metabolism study also indicate a half

- life of less than a day, suggest ing 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 prolong ed 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 p oses 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 likeli hood 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 bird s is non

- definitive (>5000 ppm ; no mortality was identified in any
of the avian studies )

. . This valuewas used to calculate an upper bound for potenti al risk, and while acute risk to birds remains an uncertainty, the potential for acute

- dose based exceedances12 of the RQ were identified

. The Agency’s calculations based on the terrestrial model T

- REX indicated greater potential chronic risks of concern. Ho wever, a s suggested above with re g ard 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 I nvertebrates 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 z one

.

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 s uch 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 condi tions that strongly favor spray drift.

Aquatic Assessment

Fish and Invertebrates

Acute r isk 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 c urrent 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

R isk estimates are below the Agency’s levels of concer n for all modeled scenarios for aquatic plants. As discussed previously EECs are primarily driven by the modeled run

- off, which
assumes no buffer betwee n 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 Bees 2 , EPA has begun to require these data where applicable. EP A 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
effect s 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

Non

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

Non

Guideline** (OECD 75) Semi

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

* Tier 1 (Laboratory

- based studies)

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

- 06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf14 **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 (EII S) 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
wh en 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

- produ cing 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 producin g the Ruston Red variety do not receive the minimum number of chilling days, which would be a significant
economic loss. W ith up to 30 % of the kiwi crop treated annually with hydrogen cyanamide, it can be considered a critical use for kiwi growers in Cali fornia. 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 Qu alitative Assessment of the Benefits of Hydrogen Cyanamide (014002), av ailable i n the public docket EPA

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, 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 report 3 outline s 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 workshop s 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 p hased, 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 Approa ches 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 agencie s 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
Decisi on 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 applica tion 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 ag encies 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 th is registration review.

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

4 http://www.epa.gov/espp/2013/nas.html16 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
chr onic 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 or gan 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, develo pmental 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 haza rd 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 estr ogen, 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 ef fect.

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 iner t ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 5 and includes some pesticides scheduled for Registration Review and chemicals found in water. Neither of these
lists should be construed as a list of k nown 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

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- 0074 for the final second list of
chemicals.

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

### I V

. 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 lan guage on the cyanamide labels are proposed
to be u p dated because t he 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 buffer s are a ppropriate 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 protec tive of estimated bystander risk

.

The Agency propose s that labels require that nozzles that produce a co a rse droplet spect rum are to be used for groundboom applications, rather than “ recommended ” as worded currently on end

use product labels , as risks associated with drift were identified for applications using fine and medium droplet size.

Appendix A of this document summar izes 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 III C of this document,

c yanamide is the only registered plant growth regulator available to ind uce 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 beli e ves that the extent to which ecological risk mitigation (e.g., 900

- foot buffer for aquatic areas, spray drift language) is already on current labe ls, and due to the limited temporal and geographic use of this chemical , there are appropriate measures currently in place

to miti gate some of the ecological risks associated with the use of cyanamide

. Additionally, the proposed requirement of coarse dro plet 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 applicat ion 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 fur ther evaluated in order to determine whether
terrestrial p lants, 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 thi s P roposed
I nterim R egistration R eview D ecision. 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

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- 1014 ) for public comment for 60 days. A Federal Register N otice will announce the availability of this P roposed I nterim R egistration R eview D ecision 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 I nterim R egistration R eview D ecision for Hydrogen Cyanamide (case 7004 ).

B. Implementation of Mitigation Measures19 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 S tandard 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. M aternal toxicity
in the rat d eve lopm e nt a l study: decreased body we i ght ga in

, decreased food co n s ump t i o n and hypoactivity in one third of the

tr ea t ed an im a l s. 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 thyroid

parathyroid 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 S572.1 7 are requiredDocket Number EPA

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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 condition s 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 noz zle 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 person s making the use r e commendation, the applicator, and the

grower. ” Directions for Use under Spray Drift Management

Replace the first paragraph under Spray Drift Management

Use Restriction ( this

remove s 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 ≥ mi l s, or Neoprene Rubber ≥ 14 mils, or Polyvinyl Chloride (PVC) ≥ 14 mils, or Viton ≥ 14
mils

• protective eyewear

A ll handlers cleaning equipment must wear :

• chemical

- resistant gloves such as Barrier Laminate, or Butyl rubber ≥ 14 mils, or Nitrile Rubber ≥ mi l s, or Neoprene Rubber ≥ 14 mils, or Polyvinyl Chloride (PVC) ≥ 14 mils, or Viton ≥ 14
mils

• chemical resistant footwear plus socks

• p rotective eyewear

• c hemical

- 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 n umber prefix TC

- 21C. Personal Protective Equipment

Replaces the current PPE list2 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

- approvedp owers air purifying respirator with an HE filter with NIOSH approval number prefix TC

- 21C.

A pplicators 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 ≥ mi l s, or Neoprene Rubber ≥ 14 mils, or Polyvinyl Chloride (PVC) ≥ 14 mils, or Viton ≥ 14
mils

• chemical resistant footwear plus socks

• p rotective eyewear .”