TABLE OF CONTENTS 

I. PRELIMINARY WORK PLAN................................................................................. 3

II. FACT SHEET ............................................................................................................. 7

III. ECOLOGICAL RISK ASSESSMENT PROBLEM FORMULATION............ 10

IV. HUMAN HEALTH EFFECTS SCOPING DOCUMENT .................................. 38

V. GLOSSARY OF TERMS AND ABBREVIATIONS............................................. 50

Page 2 of 51 
I. PRELIMINARY WORK PLAN 

Introduction:

The Food Quality Protection Act of 1996 mandated a new program: registration review. All 

pesticides distributed or sold in the United States generally must be registered by EPA, based on 

scientific data showing that they will not cause unreasonable risks to human health, workers, or 

the environment when used as directed on product labeling. The new registration review 

program is intended to make sure that, as the ability to assess 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 new registration review program, the Agency periodically 

reevaluates pesticides to make sure that as change occurs, products in the marketplace can be 

used safely. Information on this program is provided at: 

http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency has begun to implement the new registration review program, and will review each 

registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard 

for registration. The public phase of registration review begins when the initial docket is opened 

for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide 

and what additional risk analyses and data or information it believes are needed to make a 

registration review decision. After reviewing and responding to comments and data received in 

the docket during this initial comment period, the Agency will develop and commit to a final 

work plan and schedule for the registration review of hydrogen cyanamide. 

Hydrogen cyanamide is a plant growth regulator used to promote uniform bud break in fruit trees 

and vines. Hydrogen cyanamide was first registered for use in 1984. It is registered for use on 

bearing fruit trees and vines before bud break, and does not have any residential uses. 

Anticipated Risk Assessment and Data Needs:

The Agency anticipates conducting comprehensive human health and ecological risk 

assessments, including an endangered species assessment for all uses of hydrogen cyanamide. 

Ecological Risk: 

 

• The risks of concern are primarily for aquatic species and non-target terrestrial plants. 

There is also concern for indirect effects on listed species. 

• Preliminary review of Tier I plant toxicity studies indicate insufficient data on terrestrial 

plant toxicity for completion of the ecological assessment, so the Agency anticipates 

requiring Tier II vegetative vigor and seedling emergence studies. 

• The Agency does not anticipate additional fate data will be needed. 

• The planned ecological risk assessment will allow the Agency to determine whether 

hydrogen cyanamide use has “no effect” or “may affect” federally listed threatened or 

endangered species (listed species) or their designated critical habitat. If the screening 

level assessment indicates that hydrogen cyanamide “may affect” a listed species or its 

Page 3 of 51 
designated critical habitat, the assessment will be refined. The refined assessment will 

allow the Agency to determine whether the use of hydrogen cyanamide is “likely to 

adversely affect” the species or critical habitat. When an assessment concludes that a 

pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency 

will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries 

Service (Services), as appropriate. 

Human Health Risk: 

• Hydrogen cyanamide is registered as a non-food use chemical, so dietary exposure from 

food is not expected although there is the potential for exposure from drinking water. 

Therefore, the Agency plans to complete a drinking water assessment for hydrogen 

cyanamide. 

• The inhalation endpoint and dermal absorption factor for occupational risk must be 

reevaluated and margins of exposure (MOEs) will be calculated for all occupational 

exposure scenarios. A revised occupational risk assessment using the new endpoints is 

needed. 

• The Agency does not anticipate additional human health data will be needed prior to 

conducting the planned assessments. 

Timeline:

EPA has created the following estimated timeline for the completion of the hydrogen cyanamide 

registration review. 

Activities Estimated 

Year/Month 

Phase 1: Opening the docket 

Open Public Comment Period for Hydrogen Cyanamide 2007 - Dec. 

Close Public Comment Period 2008 - March 

Phase 2: Case Development 

Final Work Plan (FWP) 2008 – Apr. - June 

Issue DCI 2009 – Jan. - March 

Data Submission 2010 – Jan. - March 

Preliminary Risk Assessment and Public Comment 2011 – July - Sept. 

Close Public Comment Period 2011 – Oct. - Dec. 

Phase 3: Registration Review Decision 

Proposed Registration Review Decision 2012 – Jan. - March 

Public Comment Period 2012 – Apr. - June 

Final Registration Review Decision 

and Begin Post-Decision Follow-up 

2012 – July – Sept. 

Total (years) 5 

* Note: Only one year is required for data submission because the Tier II vegetative vigor and seedling 

emergence studies have already been conducted and submitted to the European Food Safety Authority 

(EFSA). 

Page 4 of 51 
Guidance for Commenters:

The public is invited to comment on EPA’s preliminary registration review work plan and 

rationale. The Agency will carefully consider all comments as well as any additional 

information or data provided prior to issuing a final work plan for the hydrogen cyanamide case. 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Levels (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern. 

There are no U.S. tolerances for hydrogen cyanamide, nor are there Codex MRLs; so trade 

irritants are not expected for hydrogen cyanamide. 

Hydrogen cyanamide is not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act, based on information provided at 

http://oaspub.epa.gov/tmdl/waters_list.impairments?p_impid=3. The Agency invites submission 

of water quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the “OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process” (see: http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-

sop.pdf), in order to ensure they can be used quantitatively or qualitatively in pesticide risk 

assessments. 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to hydrogen cyanamide, compared to the general population. 

Please comment if you are aware of any sub-populations that may have atypical or unusually 

high exposure compared to the general population. 

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the human health and ecological risk assessments, including any speciesspecific effects determinations. The Agency is interested in the following information: 

1. Confirmation on the following label information. 

a. sites of application 

b. formulations 

c. application methods and equipment 

d. maximum application rates in units related to mass per unit area of treatment zone 

e. frequency of application, application intervals, and maximum number of 

applications per season 

f. geographic limitations on use. 

2. Use or potential use distribution (e.g., acreage and geographical distribution of relevant 

uses). 

Page 5 of 51 
3. Use history. 

4. Median and 90th percentile reported use rates (lbs. a.i./acre) from usage data – national, 

state, and county. 

5. Application timing (date of first application and application intervals) by use – national, 

state, and county. 

6. Sub-county crop location data. 

7. Usage/use information for non-agricultural uses (e.g., golf courses, athletic fields, 

ornamentals). 

8. Directly acquired county-level usage data (not derived from state level data). 

a. maximum reported use rate (lbs. a.i./acre) from usage data – county 

b. percent crop treated – county 

c. median and 90th percentile number of applications – county 

d. total pounds per year – county 

e. the year the pesticide was last used in the county/sub-county area 

f. the years in which the pesticide was applied in the county/sub-county area 

9. Typical application interval (days). 

10. State or local use restrictions. 

11. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency. 

12. Monitoring data. 

Next Steps:

After the comment period closes, the Agency will review the comments received, and then issue 

a Final Work Plan for this pesticide. 

Page 6 of 51 
II. FACT SHEET

 

Background Information:

• Hydrogen cyanamide Registration Review Case Number: 7005 

• Hydrogen cyanamide PC Code: 014002 CAS#: 420-04-2 

• Registrants: Alzchem Trostberg GMBH, Zhejiang Tide Cropscience Co., LTD., Green 

Trees and Plants LLC 

• First product registered in 1984, therefore not subject to reregistration. 

• No food uses or tolerances. 

• Special Review and Reregistration Division (SRRD), Chemical Review Manager (CRM) 

Dana L. Friedman. friedman.dana@epa.gov 

• Registration Division (RD) Contacts: John Bazuin: bazuin.john@epa.gov 

Use & Usage Information: 

For additional details, please refer to the BEAD Appendix A document located in the hydrogen 

cyanamide docket. 

• Hydrogen cyanamide is a plant growth regulator used to promote uniform bud break in 

fruit trees and vines. 

• Based on the rapid metabolism of this chemical, residues are not expected at harvest. The 

Agency determined in 2000, all registered uses can be considered non-food uses. 

• Hydrogen cyanamide is currently registered for use under FIFRA Section 3 on the 

following bearing fruit trees and vines prior to bud-break: apples, blueberries, cherries, 

grapes (wine and raisin; kiwi fruit (California only), peaches, and nectarines. 

• Hydrogen cyanamide is formulated as a soluble concentrate and may be applied using 

airblast or backpack sprayers. 

• Hydrogen cyanamide is not registered for residential use. 

Recent Actions:

• The most recent and comprehensive human health risk assessment was conducted in 

2001, where occupational handler risks were assessed.

• In 2001 and 2003 a number of environmental fate and effects studies were submitted to 

support FIFRA Section 24(c) registrations that added uses including apple, blueberry, 

cherry, peach, and nectarine.

• Duomax, EPA Reg. No. 84374-R, is a pending end-use product, submitted in 2007. If 

approved, the registration would allow use on apples, blueberries, cherries, grapes, kiwi 

fruit, peaches, and nectarines, which are already approved uses for Reg. No. 54555-2. A 

registration decision to approve or deny this registration is expected while this comment 

period is open. 

Ecological Risk Assessment Status: 

Please refer to Section III, Ecological Risk Assessment Problem Formulation, for a detailed 

discussion of the anticipated ecological risk assessment needs. The following ecological 

outcomes and anticipated data needs are based on the limited data and risk assessments currently 

available: 

Page 7 of 51 
• Based upon the information gathered to date, the risks of concern are primarily related to 

direct effects on aquatic species and non-target terrestrial plants. There is also concern 

for indirect effects on listed species. 

• Results of Tier I aquatic modeling indicate a potential for acute and chronic risks to 

invertebrates. 

• Tier two modeling will be conducted to refine the aquatic expected environmental 

concentrations. 

• The Agency does not foresee requiring any additional environmental fate studies listed in 

CFR Part 158 prior to conducting the planned assessments. 

• Preliminary review of Tier I plant toxicity studies indicate insufficient data on terrestrial 

plant toxicity for completion of the ecological assessment, so the Agency anticipates 

requiring Tier II vegetative vigor and seedling emergence studies. The Agency is aware 

that these studies have already been submitted to the EFSA. One year will be allotted for 

submission of this data. 

• The Agency is interested in obtaining specific use information as well as monitoring data. 

These needs are outlined in Section III of this document. 

Human Health Risk Assessment Status:

Please refer to Section IV of this document, Human Health Effects Scoping Document, for a 

detailed discussion of the anticipated risk assessment needs for human health. The following is a 

summary of those anticipated needs: 

• The toxicological database for hydrogen cyanamide is adequate for the purpose of 

registration review. 

• The Agency does not foresee requiring any additional human health data prior to 

conducting the planned risk assessments. 

Dietary (Food and Water): 

• The Agency plans to conduct a drinking water exposure and risk assessment for existing 

outdoor uses of hydrogen cyanamide. As the Agency determined that all registered uses 

of hydrogen cyanamide are to be considered non-food uses, the dietary risk assessment 

will include exposures from drinking water only. 

Residential: 

• There are no registered residential uses of hydrogen cyanamide; therefore, no residential 

risk assessment is needed.

Occupational: 

• The inhalation endpoint and the dermal absorption factor need to be re-evaluated, thus, 

the MOEs in the previous occupational risk assessment may no longer be adequate. A 

revised occupational risk assessment using newly selected endpoints is needed. 

• The Agency anticipates revising the human health assessment. 

Page 8 of 51 
Incidents:

• The Agency received two ecological incident reports for cyanamide, both citing damage 

to crops. Defoliation of lemon trees was reported in 1993 in conjunction with spray drift 

that had allegedly resulted from an application to grapes made during stormy weather. 

Kiwi vine damage was reported in 2001, allegedly from direct application of hydrogen 

cyanamide. 

• There was one human health-related incident reported for hydrogen cyanamide in the 

National Institute of Occupational Safety and Health Sentinel Event Notification System 

for Occupational Risks (NIOSH/SENSOR). A 40-year old male reported symptoms of 

muscle weakness, malaise, and coughing after exposure to drift from a field. 

• There were no incidents cited in the American Association of Poison Control Center 

(AAPCC) data or the OPP Incident Data System (IDS). 

 

Data Call-In Status:

No Data Call-In has been issued for hydrogen cyanamide. 

Tolerances: 

Currently no U.S. tolerances or Mexican, Canadian, or CODEX MRLs exist for hydrogen 

cyanamide. 

Labels: 

A list of registration numbers is included below and the labels can be obtained from the Pesticide 

Product Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home. 

Hydrogen Cyanamide Registration Numbers:

Registration # Product name Company Name Active Ingredient 

54555-2 Dormex Alzchem Trostberg GMBH Hydrogen Cyanamide 

80679-6 Krop-Max Zhejiang Tide Cropscience 

Co., LTD. Hydrogen Cyanamide 

84374-R Duomax Green Trees and Plants 

LLC Hydrogen Cyanamide 

CA040002 Dormex Alzchem Trostberg GMBH Hydrogen Cyanamide 

GA030006 Dormex Alzchem Trostberg GMBH Hydrogen Cyanamide 

HI030003 Dormex Maui’s Winery/Tedeschi 

Vineyards Hydrogen Cyanamide 

Page 9 of 51 
 

III. ECOLOGICAL RISK ASSESSMENT PROBLEM FORMULATION 

Page 10 of 51 

Registration Review 

Ecological Risk Assessment 

Problem Formulation for: 

Cyanamide 

H2N-C≡N 

Prepared By: 

William P. Eckel, Ph.D., Senior Scientist 

Carolyn Hammer, Environmental Scientist 

Environmental Risk Branch 2 

Approved By: 

Dana Spatz, Acting Chief 

Environmental Risk Branch 2 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

Page 12 of 51 
STRESSOR SOURCE AND DISTRIBUTION 

Hydrogen cyanamide, (Dormex, EPA Reg. No. 54555-2) is a restricted use plant growth 

regulator currently registered (under Section 3 of FIFRA) for use on apples, blueberries, cherries, 

grapes (wine and raisin; desert; non-desert) kiwi fruit (California only), peaches and nectarines. 

It is registered under FIFRA section 24c on the following crops: blackberries in Georgia 

(GA03000600), figs in California (CA04000200) and grapes in Hawaii (HI03000300). 

Hydrogen cyanamide is applied as a single airblast or backpack spray to the plant buds 

approximately 30 days before bud break to synchronize blossoming and/or produce a more 

uniform bud break in plants that have received less than their full chill hour requirement. The 

maximum label rates are presented in Table 1. 

Table 1. Maximum label rates for cyanamide 

Use Site Max. 

Rate 

per App 

 Max. 

Rate 

Unit/Ar

ea 

*UG 

Form Max.#

Apps 

cc & 

yr 

Max. 

App 

Rate/ 

cc & yr 

 Min. 

App 

 Interval 

 (days) 

 Application 

Equipment 

 //Type 

(Reg # Code) 

FOOD/FEED 

USES 

apple 34.4 lb A SC/L NS NS NS Sprayer 

//Spray (a) 

blackberry 12.9~ lb A SC/L NS NS NS Sprayer 

//Spray (a) 

blueberry 12.9 lb A SC/L NS NS NS Sprayer 

//Spray (a) 

cherry 34.4 lb A SC/L NS NS NS Sprayer 

//Spray (a) 

fig 34.4~ lb A SC/L 1/cc NS NS Sprayer 

//Spray (a) 

grapes 34.4~ lb A SC/L NS NS NS Sprayer 

//Spray (a) 

kiwi fruit 34.4 lb A SC/L NS NS NS Sprayer 

//Spray (a) 

nectarine 12.9 lb A SC/L NS NS NS Sprayer 

//Spray (a) 

peach 12.9 lb A SC/L NS NS NS Sprayer 

//Spray (a) 

Page 13 of 51 
INTEGRATION OF AVAILABLE INFORMATION 

The risk assessments available in the docket, and which serve as the basis for this problem 

formulation, include the following: 

y August 26, 1993 Hydrogen cyanamide. Memo of Understanding Concerning the 

classification of the Use of Hydrogen Cyanamide as a Plant Growth Regulator on Dormant 

Grape Vines as a Non- Food Use 

y December 3, 1993 Hydrogen Cyanamide Risk Characterization Document, California 

Department of Pesticide Regulation. 

ECOLOGICAL EFFECTS 

Toxicity Studies 

Aquatic Toxicity, Acute. 

The acute toxicity (48-hour EC50) of cyanamide to the freshwater invertebrate Daphnia magna is 

3.3 ppm ai, which classifies it as highly toxic (Acc. No. 073728). 

A shell deposition test (MRID 448047-04) indicated a 96-hour EC50 of 2.3 ppm ai, classifying 

hydrogen cyanamide as moderately toxic to the Eastern oyster. The NOEC was 0.56 ppm. 

The 96-hour LC50 for mysids (estuarine invertebrate) exposed to hydrogen cyanamide was 6.3 

ppm ai, which classifies this compound as moderately toxic to Mysidopsis bahia. The NOEC 

was 1.4 ppm ai (MRID 448047-03). 

For the sheepshead minnow (estuarine fish), the 96-hour LC50 was determined to be 58 ppm ai, 

which classifies hydrogen cyanamide as slightly toxic. The NOEC was determined to be 26 ppm 

ai (MRID 448047-02). 

For the bluegill sunfish (warm freshwater fish), the 96-hour LC50 was determined to be 88 ppm 

ai (Acc. No. 073728). For rainbow trout (cold freshwater fish) the 96-hour LC50 is 46 ppm ai 

(MRID 073728). These results classify cyanamide as slightly toxic to fish. 

A literature study (Ecotox ref. 18390) of acute toxicity in rainbow trout (cold freshwater fish) 

indicated an LC50 of 1.93 millimolar, or 81.25 ppm ai, which classifies cyanamide as slightly 

toxic to fish. The European Food Safety Agency (EFSA, 2006) has also reported the 96-hour 

LC50 for rainbow trout as “less than” 64.8 ppm, and the 21-day LC50 to be 11.8 ppm, with a 

NOEC of 7.5 ppm. 

EFSA (2006) reported the LC50 for the carp (Cyprinus carpio) to be 80.9 mg/L, with a NOEC of 

29.9 mg/L. 

Page 14 of 51 
Aquatic Toxicty, Chronic. 

Guideline data (MRID 44076702) indicate that Cyanamide (50% ai) is highly toxic to daphnid 

growth and reproduction of young. The most sensitive endpoint was adult length after 21 days 

of exposure (LOEC=210 ppb and NOEC = 100 ppb). Numbers of young produced per female 

per reproduction day was affected at a concentration of 410 ppb. 

EFSA (2006) reports a 28-day study on the emergence, growth and development of the midge, 

Chironomus riparius. The lowest effect levels were for development: NOEC = 6.6 mg ai/L and 

LOEC = 11.2 mg ai/L. 

An Early Life Stage test in rainbow trout (MRID 44076701) indicated a LOEC :<0.507 ppm for 

growth effects and <4.03 ppm for reproduction, NOEC:<0.507 ppm for growth effects and 2.03 

ppm for reproduction. Parameters affected included weight, length, days to hatch, days to 

swimup, hatch survival. This study was rated supplemental because a true NOEC was not 

established. 

Aquatic Plant toxicity 

EFSA (2006) has reported the 90.5-hour EC50 for growth inhibition in the alga Selenastrum 

capriconutum to be 13.5 ppm, with a NOEC of 1.0 ppm. The 96-hour EC50 for growth (cell 

density) in Pseudokirchneriella subcapitata was reported to be 6.7 ppm, with a NOEC of 2.6 

ppm. For Anabaena flos aquae, the 72-hour EC50 for biomass was 0.67 ppm (NOEC 0.05 ppm), 

and the EC50 for growth rate was 0.65 ppm (NOEC 0.11 ppm). 

EFSA (2006) reported the 7-day EC50 for duckweed (Lemna gibba) to be 2.33 mg ai/L (based 

on biomass endpoint), with a NOEC of 0.5 mg ai/L. 

Terrestrial Animals: Birds

The oral LD50 for the bobwhite quail was determined to be 173 mg/kg (Acc. No. 073728), 

classifying it as moderately toxic. The 8-day dietary LC50 for both mallard duck and bobwhite 

quail was determined to be greater than 5000 ppm (MRID 42178401, 42178402), which 

categorizes cyanamide as practically non-toxic on a sub-acute dietary basis. 

A reproductive study reported by the European Food Safety Agency (2006) showed no adverse 

effects in bobwhite quail up to 300 ppm in the feed. 

Terrestrial Animals: Mammals

The acute oral LD50 for the laboratory rat is 300 mg/kg (Acc. No. 073726), which classifies 

cyanamide as moderately toxic. 

Page 15 of 51 
A two-generation rate reproduction study established a NOEL of 25 ppm or 1.25 mg/kg/day. 

The endpoints affected were decreases in maternal body weight gain and decreased food 

consumption. 

Terrestrial Invertebrates

An acute contact toxicity study (MRID 438669- 02) showed that cyanamide is essentially nontoxic to the honey bee (LD50 >36.2 μg ai/bee, and NOEL approximately 12 μg ai/bee.) 

Terrestrial Plants

EFSA (2006) reports the results of Tier 2 Seedling Emergence and Vegetative Vigor studies for 

Cyanamide L 500 (51.1% ai). The results, adjusted for percent active ingredient, and converted 

to pounds per acre, are given below. The results are expressed as EC50 (50% effective 

concentration). Under USEPA guidelines, the results of such tests are reported as EC25. 

Table 2. Tier 2 Seedling Emergence results 

Plant Genus, species NOEL, 

 lb ai/acre 

EC50, 

lb ai/acre 

Most Sensitive 

Parameter 

Monocots 

Corn Zea mays > 14.7 > 14.7 Shoot dry 

weight, height 

Oat Avena Sativa > 14.7 > 14.7 Shoot dry 

weight, height 

Onion Allium cepa 0.031 0.79 

Perennial 

ryegrass 

Lolium perenne 36.6 > 14.7 Shoot dry weight 

Dicots 

Cabbage Brassica oleracea 0.092 2.80 Shoot dry weight 

Carrot Daucus carota 9.33 440 Shoot height 

Cucumber Cucumis sativus 6.66 35.4 Shoot height 

Lettuce Lactuca sativa 35.1 35.1 Shoot dry weight 

Tomato Lycopersicon 

esculentum 

2.34 8.47 Shoot dry weight 

Shoot dry weight was the most sensitive seedling emergence endpoint. Allium cepa (onion) was 

the most sensitive plant, with an EC50 value of 0.79 lb ai/acre for cyanamide applied directly to 

the soil. 

Page 16 of 51 
Table 3. Tier 2 Vegetative Vigor results 

Plant 

Genus 

(species) 

NOEL 

lbs 

ai/acre 

EC50 

lbs 

ai/acre Endpoint 

EC50 

lbs 

ai/acre Endpoint 

Monocots 

Corn Zea mays 7.1 26.8 

shoot dry 

weight >28.6 

shoot 

height 

Onion Allium cepa 7.1 70.5 

shoot dry 

weight 1527.5 

shoot 

height 

Dicots 

Cabbage 

Brassica 

oleracea 14.3 26.3 

shoot dry 

weight >28.6 

shoot 

height 

Cucumber 

Cucumis 

sativus 1.8 9.8 

shoot dry 

weight 14.0 

shoot 

height 

Lettuce Lactuca sativa 3.6 13.4 

shoot dry 

weight >14.3 

shoot 

height 

Soybean Glycine max 7.1 15.6 

shoot dry 

weight >28.6 

shoot 

height 

Tomato 

Lycopersicon 

esculentum <0.89 3.1 

shoot dry 

weight 14.8 

shoot 

height 

The most sensitive vegetative vigor endpoint was an EC50 of 3.1 lb/acre for shoot dry weight in 

the tomato. 

Incident Reports 

The Agency has received only two ecological incident reports for cyanamide. Both incidents 

involved damage to crops. In 1993, a spray application of cyanamide to grapes made during 

stormy weather allegedly resulted in spray drift that caused defoliation of lemon trees in several 

nearby groves (I000423-001). In 2001, damage allegedly occurred to kiwi vines following direct 

treatment during winter months with cyanamide and an aliphatic petroleum solvent (I016036-

022). The Agency has received no report of any adverse field effects to animals that have been 

attributed to the use of cyanamide. The Agency also has received no incident report from 

pesticide registrants concerning cyanamide contamination of ground or surface water. 

A lack of reported incidents does not necessarily mean that such incidents have not occurred. In 

addition, incident reports for non-target plants and animals typically provide information on 

mortality events only. Reports for other adverse effects, such as reduced growth or impaired 

reproduction, are rarely received. 

Page 17 of 51 
EXPOSURE CHARACTERISTICS 

The available environmental fate data for hydrogen cyanamide indicate that it is not persistent in 

soil or water, and is not expected to partition into air except by spray drift at the time of 

application. Abiotic degradation processes (hydrolysis and photolysis) are not important, as 

metabolism is much quicker. Cyanamide is completely miscible with water, and in batch 

equilibrium experiments less than 2% of the mass adsorbed to sandy and silt loam soil. Thus, it 

is expected to be very mobile in soil-water systems. The degradates of cyanamide include 

simple nitrogen compounds (dicyanodiamide, guanylurea, guanidine, and urea) which are readily 

utilized as plant nutrients. 

Table 4. Fate Properties of Cyanamide 

Property Value Source 

Aqueous 

solubility 

Completely 

miscible 

Vapor Pressure 0.005 mmHg 

Henry’s Law 

constant 

6.15E-06 atmm3

/mol 

EFGWB oneliner database 

3/24/1993 

Hydrolysis halflife pH 5: 237 days 

pH 7: 66 years 

pH 9: 105 days 

EFGWB oneliner database 

3/24/1993 

Aqueous 

photolysis halflife 

29 days in pH 5 

and pH 7 buffers 

at 25o

C 

MRID 42178409 

Aerobic soil 

metabolism 

Less than 10 

days in moist 

soil; 12 hours in 

sandy loam soil 

MRID 42178410 

Soil partitioning <2% adsorption 

in sandy, sandy 

loam, and silt 

loam soils 

MRID 

42178415, 

42178414 

Anaerobic Soil 

Metabolism 

35-day half life in 

sandy loam soil 

MRID 42178412 

Aerobic Aquatic 

Metabolism 

Data review 

pending 

CHARACTERISTICS OF ECOSYSTEMS POTENTIALLY AT RISK 

For cyanamide and pesticides in general, the ecosystems at risk are those in close proximity to 

the use areas. These would include agricultural fields (orchards and vineyards in this case), 

surrounding terrestrial habitats, and water bodies directly adjacent to treated fields that may 

receive chemical residues via drift, volatilization, or runoff. Within water bodies, the water 

column, sediment, and pore water are all compartments of concern, however, given cyanamide’s 

solubility it is most likely to be found in the water column. 

Page 18 of 51 
Table 5 gives estimates of the national-level usage of cyanamide. More than half of the usage 

was on grapes, followed by cherries, blueberries, kiwifruit, apples, figs, and prunes/plums. All 

reported use for figs and kiwifruit was from California; these crops are registered under special 

local needs labels (FIFRA section 24c labels) in that state. The maps in Figure 1 show where the 

registered crops were grown in 1997 in the continental U.S. Taken together, the usage and crop 

locations give an indication of which environments are potentially at risk from cyanamide use. 

Organisms of concern include birds, mammals, reptiles, fish, and terrestrial and aquatic 

invertebrates, plants, and amphibians. Based on the known effects of cyanamide, terrestrial 

plants may be the primary concern. 

The assessment endpoints are intended to reflect population sustainability and community 

structure within ecosystems and hence relate back to ecosystems at risk. If risks are expected for 

given species/taxa based on the screening-level assessment, then risks might be expected to 

translate to higher levels of biological organization. 

 

Table 5 

Screening Level Estimates of Agricultural Uses of Cyanamide 014002 

Sorted Alphabetically 

(4-25-07) 

Crop Lbs. A.I Percent Crop Treated. 

 

 Avg. Max. 

 1 Apples 4,000 <1 <2.5 

 2 Blueberries 20,000 10 10 

 3 Cherries 30,000 5 10 

 4 Figs * 2,000 N/C N/C 

 5 Grapes 100,000 <1 <2.5 

 6 Kiwifruit * 10,000 N/C N/C 

 7 Prunes & Plums <500 N/C N/C 

All numbers rounded. 

'<500' indicates less than 500 pounds of active ingredient. 

'<2.5' indicates less than 2.5 percent of crop is treated. 

'<1' indicates less than 1 percent of crop is treated. 

* CA data only, but 95% or more of U.S. acres are in California 

N/C: Not Calculated 

Note: 

OPPIN does not include “Prunes & Plums” as registered uses for Cyanamide. 

OPPIN does include “Nectarines” and “Peaches” as registered uses for Cyanamide but no usage 

has been observed in our usage databases. 

Page 19 of 51 
Figure 1. Major Growing Areas in the U.S. Source: USDA Economic Research Service, 

http://maps.ers.usda.gov/AgResources/, accessed July 31, 2007. 

Apples, Total Acres, 1997 

Legend

(acres) 

1.0-6.0 

6.0-18.0 

18.0-44.0 

44.0-156.0 

156.0-75,264. 

Page 20 of 51 
Blackberries, pounds Harvested, acres, 1997 

Legend

(acres) 

1.0-1.0 

1.0-3.0 

3.0-5.0 

5.0-11.0 

11.0-2,935 

Page 21 of 51 
Tame blueberries harvested, acres, 1997 

Legend

(acres) 

1.0-4.0 

4.0-8.0 

8.0-19.0 

19.0-51.0 

51.0-6,635 

Page 22 of 51 
Cherries, total acres, 1997 

Legend

(acres) 

1.0-1.0 

1.0-3.0 

3.0-9.0 

9.0-66.0 

66.0-13,456 

Page 23 of 51 
Figs, total acres, 1997 

Legend

(acres) 

1.0-1.0 

1.0-1.0 

1.0-3.0 

3.0-9.0 

9.0-12,396 

Page 24 of 51 
Grapes, fresh weight, total acres, 1997 

Legend

(acres) 

1.0-1.0 

1.0-4.0 

4.0-11.0 

11.0-50.0 

50.0-265,544 

Page 25 of 51 
Kiwifruit, total acres, 1997 

Legend

(acres) 

2.0-4.0 

4.0-13.0 

13.0-37.0 

37.0-104.0 

104.0-1,533 

Page 26 of 51 
Nectarines, total acres, 1997 

Legend

(acres) 

1.0-3.0 

3.0-9.0 

9.0-30.0 

30.0-116.0 

Page 27 of 51 
Peaches, total acres, 1997 

Legend

(acres) 

1.0-3.0 

3.0-10.0 

10.0-25.0 

25.0-73.0 

73.0-15,885. 

Page 28 of 51 
ASSESSMENT ENDPOINTS 

Assessment endpoints are defined as “explicit expressions of the actual environmental value that 

is to be protected.” Defining an assessment endpoint involves two steps: 1) identifying the 

valued attributes of the environment that are considered to be at risk; and 2) operationally 

defining the assessment endpoint in terms of an ecological entity (i.e., a community of fish and 

aquatic invertebrates) and its attributes (i.e., survival and reproduction). Therefore, selection of 

the assessment endpoints is based on valued entities (i.e., ecological receptors), the ecosystems 

potentially at risk, the migration pathways of pesticides, and the routes by which ecological 

receptors are exposed to pesticide-related contamination. The selection of clearly defined 

assessment endpoints is important because they provide direction and boundaries in the risk 

assessment for addressing risk management issues of concern. Changes to assessment endpoints 

are typically estimated from the available toxicity studies, which are used as the measures of 

effects to characterize potential ecological risks associated with exposure to a pesticide, such as 

cyanamide. 

To estimate exposure concentrations, the ecological risk assessment considers a single 

application at the maximum application rate to fields that have vulnerable soils. The most 

sensitive toxicity endpoints are used from surrogate test species to estimate treatment-related 

direct effects on acute mortality and chronic reproductive, growth and survival assessment 

endpoints. Toxicity tests are intended to determine effects of pesticide exposure on birds, 

mammals, fish, terrestrial and aquatic invertebrates, and plants. These tests include short-term 

acute, sub-acute, and reproduction studies and are typically arranged in a hierarchical or tiered 

system that progresses from basic laboratory tests to applied field studies. The toxicity studies 

are used to evaluate the potential of a pesticide to cause adverse effects, to determine whether 

further testing is required, and to determine the need for precautionary label statements to 

minimize the potential adverse effects to non-target animals and plants. 

Data on the toxicity of cyanamide to aquatic and terrestrial plants has been submitted to the 

Agency, but has not yet been reviewed for validity. However, given the registered use of 

cyanamide as a plant growth regulator, and warnings on the label regarding leaf loss and blossom 

loss in adjacent crops, adverse effects on terrestrial plants are expected to be a major focus of the 

risk assessment. 

In terms of direct effects to terrestrial plants, both dicots and monocots are sensitive to 

cyanamide. Tests performed using the hydrogen cyanamide indicated that cabbage was the most 

sensitive dicot to hydrogen cyanamide , with shoot dry weight, as measured during a seedling 

emergence test, as the most sensitive endpoint (NOEC = 0.092 lbs. a.i./A, EC25 = 2.80 lbs. 

a.i./A). Onion was the most sensitive monocot, with an EC50 of 0.79 lbs. a.i./A and an NOAEL 

of 0.031 lbs. a.i./A in seedling emergence tests. 

Because of the potential risk to listed and non-listed plants, unicellular algae, aquatic 

invertebrates, birds, and mammals, should exposure occur, listed species in all taxa may 

potentially be affected indirectly due to alterations in their habitat (e.g., food sources, shelter, and 

areas to reproduce). 

Page 29 of 51 
Because of the application timing for cyanamide (30 days before bud break), applications will 

occur in the winter and early spring. Thus, toxic effects are expected to occur mostly in 

evergreen plants (e.g., citrus). Leaf loss has been noted in lemon trees exposed to cyanamide. A 

spray drift buffer to prevent adverse effects in plants will need to be calculated. 

Based on a preliminary analysis of exposure, there may be a concern for direct, acute and chronic 

effects in freshwater invertebrates. This may in turn have indirect effects on consumers of 

invertebrates such as fish and amphibians via a reduction in available food items. 

CONCEPTUAL MODEL 

In order for a chemical to pose an ecological risk, it must reach ecological receptors in 

biologically significant concentrations. An exposure pathway is the means by which a pesticide 

moves in the environment from a source to an ecological receptor. For an ecological exposure 

pathway to be complete, it must have a source, a release mechanism, an environmental transport 

medium, a point of exposure for ecological receptors, and a feasible route of exposure. 

The conceptual model (Figure 2) depicts the potential pathways for ecological risk associated 

with hydrogen cyanamide use. The conceptual model provides an overview of the expected 

exposure routes for organisms within the hydrogen cyanamide action area. For terrestrial 

organisms, the major route of exposure considered is the dietary route; consumption of food 

items such as plant leaves or insects that have cyanamide residues as a result of spraying, drift, 

and volatilization. Inhalation and dermal exposure may also be important exposure routes, as 

cyanamide is known to be irritating to the eyes, skin, and respiratory tract. For aquatic animal 

species, the major routes of exposure are considered to be via the respiratory surface (gills) or the 

integument. Direct contact and/or root uptake is the major route of exposure for terrestrial and 

wetland (riparian) plants, while aquatic plants may be exposed via direct uptake and adsorption. 

Estimated exposure concentrations for all organisms are obtained through the use of several 

Agency exposure models. 

Risk Hypothesis 

Based on an examination of the physical/chemical properties of hydrogen cyanamide, the fate 

and disposition in the environment, and mode of application, a conceptual model was developed 

that represents the possible relationships between the stressor, ecological receptors, and the 

assessment endpoints. The major transport pathways for hydrogen cyanamide are spray drift and 

run-off, resulting in exposure to various terrestrial and aquatic receptors. The Agency has 

received only two ecological incident reports for cyanamide. Both incidents involved damage to 

crops. The Agency has received no report of any adverse field effects to animals that have been 

attributed to the use of cyanamide. The Agency also has received no incident report from 

pesticide registrants concerning cyanamide contamination of ground or surface water. Based 

upon the information gathered to date, the risks of concern are primarily related to direct effects 

on aquatic species and non-target terrestrial plants. Additionally, there is concern for indirect 

effects on listed species. 

Page 30 of 51 
Figure 2. Ecological conceptual diagram for Hydrogen Cyanamide 

Hydrogen Cyanamide Applied to Fruit Trees, Bushes or Vineyards STRESSOR

Volatilization/ 

Wind Suspension

Spray Drift Runoff/ Erosion Leaching (Infiltration)/ 

Percolation

Direct Deposition SOURCE/ 

TRANSPORT 

PATHWAYS

Terrestrial Food 

Residues (foliage, 

food, insects)

Upland 

Foliage/ Soil

Riparian/ 

Wetland 

Foliage/ Soil

Receiving 

Water Body/ 

Sediment

Groundwater

Terrestrial 

Upland 

Plants

Riparian/ 

Wetland 

Plants

Terrestrial Vertebrates 

(Birds, Mammals, 

Reptiles, Terrestrial 

Phase Amphibians)

Aquatic 

Plants

Aquatic 

Invert. & 

Vertebrates

Plant 

Population 

Reduced 

Population 

Growth

Individual Animals 

Reduced Survival, 

Growth, Reproduction, 

Individual 

Invertebrates, 

Vertebrates 

Reduced Survival, 

Growth, 

Reproduction

Individual Plants 

Reduced Seedling 

Emergence, 

Vegetative Vigor

Ingestion 

Inhalation

Dermal Direct Contact Root 

Uptake

Uptake/ 

Adsorption

Gill/ 

Integument 

Uptake

Direct Contact/ 

Root Uptake

SOURCE/ 

EXPOSURE MEDIA

EXPOSURE ROUTE

RECEPTORS

ATTRIBUTE 

CHANGE

ANALYSIS PLAN OPTIONS

In Registration Review, pesticide ecological risk assessments will follow the Agency’s 

Guidelines for Ecological Risk Assessment, will be in compliance with the paper titled 

“Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. 

Environmental Protection Agency” (“Overview Document”) (January 2004), and will be done in 

accordance with Section 7 of the Endangered Species Act. 

Previously completed screening level risk assessments and exceedences of Agency levels of 

concern indicate a need to further examine and refine acute risk to terrestrial and aquatic plants. 

Spray drift buffers (300 yards) are currently based on effects to aquatic ecosystems, but need to 

be revisited based on effects data for both aquatic species and terrestrial plants, and quantitative 

exposure estimates. Finally, analysis of potential indirect effects on listed species is required. 

The Agency wishes to better understand the potential for adverse effects via dermal and 

inhalation exposure routes, since cyanamide is known to be irritating via these routes. 

Table 4 shows the current status of risk assessments for registered uses of hydrogen cyanamide. 

The inputs for aquatic exposure modeling in previous assessments were based on different 

Page 31 of 51 
assumptions that may affect the resulting RQ values. In addition to refining the terrestrial plant 

risk assessment, other uncertainties and potential paths forward are described below. 

y A series of terrestrial (tier one) and aquatic plant toxicity studies were submitted and are 

under review. Upon initial screening, the results of the terrestrial plant toxicity studies 

indicate that a Tier II analysis will be required. The Tier I studies are the same that are 

referenced in the EFSA (2006) assessment. The EFSA assessment also includes the results 

of Tier II vegetative vigor and seedling emergence studies by the same authors as the Tier I 

studies. In the EFSA assessment, the toxicity endpoints reported in each of the terrestrial 

plant studies are the NOAEL and EC50. It is EFED policy to evaluate risks to plants using 

the NOAEL/NOAEC and the EC25. The raw data from the Tier II study would be needed in 

order to calculate the appropriate endpoint (EC25). Risk to plants will be assessed using the 

TerrPlant model. The following studies have been submitted to fulfill these guideline 

requirements and are currently under review: 

y 45380701 Meister, A. (2000) Effects of Cyanamide L 500 on the Vegetative 

Nontarget Plant Species: Tier I: Vegetative Vigor Limit Test: Final Report: Lab 

Project Number: 7042087: 851-002. Unpublished study prepared by Institut fur 

Biologische Analytik und Consulting IBACON GmbH. 64 p. {OPPTS 850.4150} 

y 45380702 Meister, A. (2000) Effects of Cyanamide L 500 on the Seedling 

Emergence of Nontarget Plant Species: Tier I: Seedling Emergence Limit Test: Final 

Report: Lab Project Number: 7041086: 851-001. Unpublished study prepared by 

Institut fur Biologische Analytik und Consulting IBACON GmbH. 89 p. {OPPTS 

850.4100} 

y 45382201 Hertl, J. (2000) Toxicity of SKW Cyanamide L 500 to Anabaena flosaquae in an Algal Growth Inhibition Test: Final Report: Lab Project Number: 

6677210. Unpublished study prepared by Institut fur Biologische Analytik und 

Consulting IBACON GmbH. 78 p. 

y 45382202 Volkl, S. (2000) (Carbon 14)-Cyanamide Route and Rate of Degradation 

in Aerobic Aquatic Systems: Lab Project Number: 744952. Unpublished study 

prepared by RCC, Ltd. 177 p. 

y 45406601 Seyfried, B. (2000) Toxicity of Cyanamide L 500 to Pseudokirchneriella 

subcapitata (Formerly Selenastrum capricornutum) in a 96-Hour Algal Growth 

Inhibition Test: Lab Project Number: 744963. Unpublished study prepared by RCC 

Ltd. 76 p. {OPPTS 850.5400} 

y 45406602 Hertl, J. (2000) Toxicity of SKW Cyanamide L 500 to the Aquatic Plant 

Lemna gibba in a Growth Inhibition Test: Final Report: Lab Project Number: 

6679240. Unpublished study prepared by Institut fur Biologische Analytik und 

Consulting IBACON GmbH. 76 p. {OPPTS 850.4400} 

Page 32 of 51 
y Results of Tier one aquatic exposure modeling (GENEEC) indicate the potential for acute 

and chronic risk to invertebrates. Tier two modeling (PRZM/EXMS) will be conducted to 

refine the aquatic expected environmental concentrations (EECs). 

y Cyanamide is mobile and not expected to be persistent in water. Therefore, chronic exposure 

to organisms that inhabit the water column would require repeated applications of 

cyanamide. Because only one application per crop cycle is allowed, it is unlikely that 

chronic aquatic exposure will occur. 

An early life stage test in rainbow trout (MRID 44076701) was submitted. While the study 

was scientifically sound, it was classified as supplemental because effects were observed at 

all concentrations tested, and therefore a true NOEC could not be established. The authors of 

the study responded that a NOEAC could be statistically determined and the study should 

therefore fulfill the guideline. After consideration of the issue by the EFED Aquatic Biology 

Technical Team, a NOEAC value was estimated and accepted by EFED (Memo, October 8, 

1999). A NOAEC of 0.8 ppm for rainbow trout will be used to evaluate the effects of 

chronic exposure to freshwater fish. The results of a long-term exposure study with the 

midge were included in the EFSA (2006) report and will be considered in the risk 

characterization. There are no chronic effects data for estuarine/marine fish or invertebrates. 

In the absence of this data, estuarine/marine animals will be assumed to be as sensitivite to 

cyanamide as freshwater species. It is possible that this assumption will underestimate risk 

and this uncertainty can only be allievated by chronic toxicity data for saltwater species. 

There are very few chemical compounds with a similar structure or mode of action. In some 

cases, EFED uses toxicity data from similar compounds to estimate the relative sensitivity of 

freshwater and saltwater species. Because there are so few chemicals, which have limited 

data sets, this method will not be used. 

y Cyanamide is classified as practically non-toxic to birds on an acute oral basis. However, as 

discussed in the 1993 assessment, high application rates (6.45 to 34 lbs ai/A) resulted in LOC 

exceedances, indicating the potential for risk to birds. At the time of the previous 

assessment, no avian reproductive toxicity data had been submitted. Reproductive effects are 

expected based on the magnitude of acute LOC exeedances. A recently submitted study of 

bobwhite quail reproductive effects is currently under review and this study will help to 

clarify the potential for reproductive effects to birds. 

y Cyanamide is classified as moderately toxic to mammals on an acute basis, but like birds, the 

high application rates result in LOC exeedances indicating the potential for risk to mammals. 

Risks to birds, mammals and insects will be evaluated using TREX. Additionally, indirect 

effects to birds and mammals due to effects on plant species will be considered. 

y The product label specifies a buffer of 300 yards between the edge of the application area and 

any water bodies to protect wildlife and plants. Using tier II models, PRZM/EXMS, AgDrift, 

and AgDisp, this buffer will be re-evaluated. Organisms of concern include aquatic 

invertebrates and plants. The appropriate buffer to protect each of these taxa will be 

calculated separately. 

Page 33 of 51 
If the planned ecological risk assessment indicates that cyanamide may potentially impact, either 

directly or indirectly, listed species or critical habitat, and therefore does not support a “not likely 

to adversely affect” determination, further refinements will be made. This will involve 

determining whether use of cyanamide “may affect” a particular listed species, and if so, whether 

it is “likely to adversely affect” the species, or in the case of critical habitat, whether use of the 

pesticide may destroy or adversely modify any principle constituent elements for the critical 

habitat, and if so, whether the expected impacts are “likely to adversely affect” the critical 

habitat. The first step in the process is to improve the exposure estimates based on refining the 

geographic proximity of cyanamide’s use and the listed species and/or critical habitat. If there is 

no geographic proximity, this information would support a determination that cyanamide use 

will have no effect on the species or critical habitat. If after conducting the first step of this 

analysis the Agency determines that geographic proximity exists, both potential direct effects 

and any potential indirect effects of the pesticide use will be examined. This process is 

consistent with the Agency's Overview Document. The Agency will consult as necessary with 

the U.S. Fish and Wildlife Service and National Marine Fisheries Service (Services), consistent 

with the Services' regulations. 

If the screening level risk assessment identifies potential concerns for indirect effects on listed 

species for those organisms dependent upon terrestrial plants, the next step for EPA and the 

Services would be to identify which listed species and critical habitat are potentially implicated. 

Analytically, the identification of such species and critical habitat can occur in either of two 

ways. First, the agencies could determine whether the action area overlaps critical habitat or the 

occupied range of any listed species. If so, EPA would examine whether cyanamide’s potential 

impacts on non-endangered species would affect the listed species indirectly or directly affect a 

constituent element of the critical habitat. Alternatively, the agencies could determine which 

listed species depend on biological resources, or have constituent elements that fall into, the taxa 

that may be directly or indirectly impacted by cyanamide. Then EPA would determine whether 

the use of cyanamide overlaps the critical habitat or the occupied range of those listed species. 

Anticipated Data Needs 

The Agency does not foresee requiring any additional environmental fate studies listed in 40 

CFR Part 158 prior to conducting the planned assessments. However, there is currently 

insufficient data on terrestrial plant toxicity to complete this assessment. Tier II vegetative vigor 

and seedling emergence studies are a data gap. There are no submitted studies of the 

reproductive effects of chronic exposure to estuarine organisms. Submission of these studies 

will reduce uncertainty. In the absence of chronic estuarine/marine toxicity data, effects to salt 

water organisms will be assumed equivalent to effects on freshwater species.

The Agency will also conduct a search of the open literature to ensure that all best available 

science is utilized. The Agency uses the ECOTOX database as its mechanism for searching the 

open literature for ecological effects information. ECOTOX integrates three previously 

independent databases - AQUIRE, PHYTOTOX, and TERRETOX - into a system which 

includes toxicity data derived predominately from the peer-reviewed literature, for aquatic life, 

terrestrial plants, and terrestrial wildlife, respectively. 

Page 34 of 51 
Terrestrial Toxicity 

y Plants, Tier II; we have received the Tier I vegetative vigor and seedling emergence 

studies, however, the data do not provide enough information to determine that there is no 

risk to plants, and therefore risk will be presumed. The raw data from the Tier II plant study 

presented in the EFSA assessment would greatly reduce this uncertainty. 

Other Information Needs 

There is specific information that will assist the Agency in refining the ecological risk 

assessment, including any species-specific effects determinations. The Agency is very much 

interested in obtaining the following information: 

1. use or potential use distribution (e.g., acreage and geographical distribution of relevant 

crops) 

2. use history 

3. median and 90th percentile reported use rates (lbs. a.i./acre) from usage data – national, 

state, and county 

4. sub-county crop location data 

5. directly acquired county-level usage data (not derived from state level data) 

a. maximum reported use rate (lbs. a.i./acre) from usage data – county 

b. percent crop treated – county 

c. median and 90th percentile number of applications – county 

d. total pounds per year – county 

e. the year the pesticide was last used in the county/sub-county area 

f. the years in which the pesticide was applied in the county/sub-county area 

6. state or local use restrictions 

7. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency 

8. monitoring data 

The analysis plan will be revisited and may be revised depending upon the data available in the 

open literature and the information submitted by the public in response to the opening of the 

Registration Review docket. 

Page 35 of 51 
Table 4 

Current Status of Ecological Risk Assessment 

For Registered Uses of Hydrogen Cyanamide 

(crop and use information provided by BEAD) 

Crop Form Application 

rate 

Previously

Assessed 

(lbs. a.i./A) 

Included in 

Previous EFED 

Screening Risk 

Assessment? 

LOC’s Exceeded in Tier I Screening 

Risk Assessment 

(?: not determined) 

RQ is in parenthesis

apple SC/L 34.4 Yes Birds: acute (0.3 to 23.86) 

Mammals: acute (0.26 to 26.14), chronic 

(20.64 to 330) 

Terrestrial Plants: ? 

 Freshwater Fish: none 

Freshwater Invertebrates: chronic (1.32) 

Estuarine/Marine Fish: ? 

E-M Invertebrates: ? 

Aquatic Plants: 

blackberry SC/L 13.2~ Yes Birds: 

Mammals: 

Terrestrial Plants: 

Freshwater Fish: none 

Freshwater Invertebrates: chronic (1.32) 

Estuarine/Marine Fish: 

E-M Invertebrates: 

Aquatic Plants: 

blueberry SC/L 6.45 Yes Birds: acute (0.06 to 4.47) 

Mammals: acute (0.05 to 4.90), chronic 

(3.88 to 61.92) 

Terrestrial Plants: ? 

Freshwater Fish: none 

Freshwater Invertebrates: none 

Estuarine/Marine Fish: ? 

E-M Invertebrates: ? 

Aquatic Plants:? 

cherry SC/L 34.4 Yes Birds: acute (0.3 to 23.86) 

Mammals: acute (0.26 to 26.14), chronic 

20.64 to 330.24) 

Terrestrial Plants: ? 

Freshwater Fish: none 

Freshwater Invertebrates: chronic (1.32) 

Estuarine/Marine Fish: ? 

E-M Invertebrates: ? 

Aquatic Plants:? 

nectarine SC/L 12.9 Yes Birds: acute (0.11 to 8.95) 

Mammals: acute 0.1 to 9.8), chronic 7.76 

to 123.84) 

Terrestrial Plants: ? 

Freshwater Fish: none 

Freshwater Invertebrates: none 

Estuarine/Marine Fish: ? 

E-M Invertebrates: ? 

Aquatic Plants: ? 

Page 36 of 51 
Crop Form Application 

rate 

Previously

Assessed 

(lbs. a.i./A) 

Included in 

Previous EFED 

Screening Risk 

Assessment? 

LOC’s Exceeded in Tier I Screening 

Risk Assessment 

(?: not determined) 

RQ is in parenthesis

peach SC/L 12.9 Yes Birds: acute (0.11 to 8.95) 

Mammals: acute (0.1 to 9.8), chronic 

(7.76 to 123.84) 

Terrestrial Plants: ? 

Freshwater Fish: none 

Freshwater Invertebrates: none 

Estuarine/Marine Fish: ? 

E-M Invertebrates:? 

Aquatic Plants: ? 

fig SC/L 17.6~ No Birds: 

Mammals: 

Terrestrial Plants: 

Freshwater Fish: 

Freshwater Invertebrates: 

Estuarine/Marine Fish: 

E-M Invertebrates: 

Aquatic Plants: 

grapes SC/L 17.6~ No Birds: 

Mammals: 

 Terrestrial Plants: 

Freshwater Fish: 

Freshwater Invertebrates: 

Estuarine/Marine Fish: 

E-M Invertebrates: 

Aquatic Plants: 

kiwi fruit SC/L 17.6 No Birds: 

Mammals: 

Terrestrial Plants: 

Freshwater Fish: 

Freshwater Invertebrates: 

Estuarine/Marine Fish: 

E-M Invertebrates: 

Aquatic Plants: 

Page 37 of 51 
IV. HUMAN HEALTH EFFECTS SCOPING DOCUMENT 

Page 38 of 51 

OSHA’s 8-hour Time Weighted Average (TWA) Threshold Limit Value (TLV) of 0.002 mg/L. 

It was believed that the 0.002 mg/L is based on human data, and that the sensitive population 

was worker who consume ethanol, therefore, the target MOE for inhalation was set at 1. 

Cyanamide was classified as a Group C chemical–a possible human carcinogen, based upon 

female mouse ovarian granulosa-theca tumor rates. Using surrogate unit exposures from the 

Pesticide Handler Exposure Database (PHED) and the maximum application rate, the estimated 

short- and intermediate- term dermal MOEs for applicators (the highest exposure scenario) are 

OSHA’s 8-hour Time Weighted Average (TWA) Threshold Limit Value (TLV) of 0.002 mg/L. 

It was believed that the 0.002 mg/L is based on human data, and that the sensitive population 

subgroup was workers who consume ethanol, therefore, the target MOE for inhalation was set at 

1. Cyanamide was classified as a Group C chemical–a possible human carcinogen, based upon 

female mouse ovarian granulosa-theca tumor rates. Using surrogate unit exposures from the 

Pesticide Handler Exposure Database (PHED) and the maximum application rate, the estimated 

short- and intermediate- term dermal MOEs for applicators (the highest exposure scenario) are 

26 and 100, respectively, at the engineering control level (target MOE ≥ 300). The cancer risk 

was calculated at 1.4E-04 at the engineering control level. 

HED’s scoping conclusions are: 1) the toxicity data base is complete. However, the endpoint 

selections may not be adequate. Depending on future drinking water assessment from EFED, 

acute and chronic dietary endpoints may be needed to assess risk from drinking water exposure. 

For dermal endpoints, although the endpoints are adequate, the dermal absorption rate is overly 

conservative. A reevaluation of the dermal absorption factor is needed. For inhalation endpoint, 

the 0.002 mg/L (=2 mg/m3) TLV is not based on human toxicity data for cyanamide, instead, it 

was recommended by ACGIH based on a rabbit study where the Antabuse- effect for cyanamide 

was found at about one-sixth that of thiram (tetramethylthiuram disulfide). Since a TLV-TWA 

of 1.0 mg/m3 was recommended for thiram by ACGIH, therefore, ACGIH recommended a 2 

mg/m3 for cyanamide. Based on the cyanamide rat developmental study, the dose for regulation 

based on developmental effects is 0.017 mg/kg/day which is lower than the ACGIH 

recommended TLV of 2 mg/m3 for cyanamide (= 0.23 mg/kg/day assuming 8 hour per day at the 

breathing rate of 1.0 m3

 /hour), and therefore, the 2 mg/m3 is less protective. A re-selection of 

the inhalation endpoint is needed for the Registration Review of cyanamide; 2) depending on 

future drinking water assessment from EFED, acute and chronic dietary assessments for drinking 

water exposure may be needed; 3) no residential assessment is needed for the Registration 

Review of cyanamide. HED recommends that a statement such as “Do not use in residential 

settings” be put on the current label under directions for use; 3) due to the need to reevaluate the 

inhalation endpoint and the dermal absorption factor as discussed above, the MOEs in the 

previous occupational risk assessment are no longer adequate. A revised occupational risk 

assessment using newly selected endpoints is needed for the Registration Review of cyanamide.

Page 40 of 51 
Introduction 

HED has evaluated the status of the human health assessments for cyanamide to determine 

whether sufficient data are available and whether a new human health risk assessment is needed 

to support Registration Review. HED has considered the most recent risk assessments for 

cyanamide (HED memo of 5/23/01, S. Weiss, D275076; HED memo of 06/12/01, J. Whalan, 

D271362; HED memo of 03/10/06, M. Collantes, D306179; and HED memo of 02/09/07, M. 

Collantes, D333780), HED database, OPPIN database, and Google online search. 

Hydrogen cyanamide is a plant growth regulator used to promote uniform bud break in fruit 

trees. Hydrogen cyanamide currently has a Section 3 registration for application on dormant 

grapes (desert and non-desert) and blueberries at a maximum application rate of 17.2 lb ai per 

acre, peaches and nectarines at 12.9 lb ai/acre, and apples, cherries, kiwis at 34.4 lb ai/acre 

(Dormex TM , EPA Reg. No. 54555-2). It has been determined that all registered uses can be 

considered non-food uses (HED memo of 3/27/00, J. Herndon, D234173 and D240030). 

Dormex TM is a liquid water soluble concentrate that contains 50% of the active ingredient 

hydrogen cyanamide (4.3 lbs ai per gallon of product). The current Dormex TM label requires the 

use of both a full-body chemical-resistant suit and that applicators use an enclosed cab. 

Chemical Identity 

As a crystalline solid, hydrogen cyanamide is combustible and deliquescent. The formulated 

product is the material tested in all toxicity studies. 

Table 1. Cyanamide Nomenclature

Chemical structure 

2NH N

Common name Cyanamide 

Empirical formula CH2N2

Molecular weight 42.04 

PC Code 014002 

IUPAC name Hydrogen cyanamide 

CAS name Hydrogen cyanamide 

CAS registry number 420-04-2 

 

Hazard Identification/Toxicology 

Based on hydrogen cyanamide’s “non-food” use pattern, the HIARC has previously determined 

that there are no toxicology data gaps. The acute toxicity categories are I for skin irritation and 

inhalation, and II for oral toxicity, dermal toxicity, and eye irritation. There are no dermal or 

inhalation toxicity studies but none are required due to the corrosive nature of cyanamide. 

Effects observed in subchronic and chronic toxicities include decreased body weight gain, 

tremors, salivation, decreased T4, increased relative thyroid-parathyroid weights, and urinary 

bladder and kidney lesions. Developmental effects were observed in rats (increased resorptions, 

decreased fetal body weight, increase in diaphragmatic hernias, and wavy/bent ribs) and rabbits 

(increased early resorptions and dead fetuses, decrease in fetal weight and size, an increase in 

Page 41 of 51 
small meningeal hemorrhages and/or hemorrhages of the olfactory bulb, and disintegration of 

liver structure), but at doses equal to or in excess of those that caused maternal effects. There are 

no reproductive toxicity concerns as the reproductive NOAEL is 12-fold greater than the parental 

NOAEL. Hydrogen cyanamide was classified as a Group C chemical–a possible human 

carcinogen, based upon female mouse ovarian granulosa-theca tumor rates in a 104-week 

drinking water study. The unit risk, Q1

*

 is 6.64 x 10-2 (mg/kg/day)-1 in human equivalents. There 

was no evidence of carcinogenicity in rats, mice, or dogs in other long-term studies. 

The only suggestion of neurotoxicity in the data base was tremors and excessive salivation in a 

chronic dog toxicity study at the LOAEL of 5 mg a.i./kg/day. These signs were not observed in 

a subchronic dog toxicity study. Parasympathetic overactivity, including miosis, excessive 

salivation, tearing, and twitching, is mentioned in the literature. The only suggestions of 

endocrine effects in the data base were decreased T4 and increased relative thyroid-parathyroid 

weights. 

Dermal endpoints were based on developmental effects such as decreased body weights, and 

reproductive effects such as decreased F1 and F2 pup viability, using an estimated dermal 

absorption factor of 11%. A 3X uncertainty factor was applied for the use of a LOAEL for 

NOAEL. The inhalation endpoint was based on an American Conference of Governmental 

Industrial Hygienists (ACGIH) Time Weighted Average (TWA) Threshold Limit Value (TLV). 

The HIARC chose to adopt the TLV–currently 0.002 mg/L–for calculating worker inhalation 

risk because HIARC considered it being protective of hydrogen cyanamide’s irritancy and 

Antabuse-effect. The HIARC believed that the 0.002 mg/L TLV concentration is based on 

human data, and that the sensitive population is known–workers that consume ethanol–and the 

TLV protects workers from the Antabuse-effect, therefore, the target MOE for inhalation was set 

at 1. 

A summary of the toxicological endpoint decisions from the most recent human health risk 

assessment of cyanamide is given in Appendix A. 

Conclusions: HED registration review scoping team has re-evaluated the above toxicity 

endpoints and dose response according to the current policies. The scoping team concluded that 

the toxicity data base is complete. However, the endpoint selections may not be adequate. No 

dietary endpoints were selected before. Depending on a future drinking water assessment from 

EFED, acute and chronic dietary endpoints may be needed to assess risk from drinking water 

only. For dermal endpoints, although the short -and intermediate- term dermal endpoints are 

adequate, the dermal absorption factor was based on 10 mg dosing (or 800 μg/cm2

) which is 

very high dosing level compared to expected human exposure levels based on maximum label 

use rate (roughly 1.44 μg/cm2

), there fore, the 11% dermal absorption previously selected is 

overly conservative, as cyanamide is a strong dermal sensitizer and skin irritant, the dermal 

absorption rates increase with the dosing levels as indicated in dermal absorption studies in rats. 

A reevaluation of the dermal absorption factor is needed. For inhalation endpoint, the 0.002 

mg/L (=2 mg/m3

) TLV is not based on human toxicity data for cyanamide, instead, it was 

recommended by ACGIH based on a rabbit study (Hald, Jacobsen, and Larsen, 1952) where 

Antabuse- effect for cyanamide (LOAEL = 460mg/kg/day) was found at about one-sixth that of 

Thiram (tetramethylthiuram disulfide). Since a TLV-TWA of 1.0 mg/m3 was recommended for 

Page 42 of 51 
Thiram by ACGIH (based on relative potential to cause irritation when compared with other 

irritants), therefore, ACGIH recommended a 2 mg/m3 for cyanamide. Based on the cited rabbit 

study, if the uncertainty factor of 1000 is added to account for interspecies sensitivity, 

intraspecies sensitivity, and LOAEL to NOAEL, the dose for this Antabuse-effects will be 0.46 

mg/kg/day, which is higher than the ACGIH recommended TLV of 2 mg/m3 for cyanamide (= 

0.23 mg/kg/day assuming 8 hour per day at the breathing rate of 1.0 m3 /hour), and therefore, 

the 2 mg/m3 is more protective. However, if the rat developmental study was considered, the 

dose for regulation based on developmental effects is 0.017 mg/kg/day which is lower than 0.23 

mg/kg/day (= TLV of 2 mg/m3 ). A re-selection of the inhalation endpoint is needed for the 

Registration Review of cyanamide. HED’s registration review scoping team concurs with 

previous decision on cancer classification where hydrogen cyanamide was classified as a Group 

C chemical–a possible human carcinogen, based upon female mouse ovarian granulosa-theca 

tumor rates in a 104-week drinking water study. The unit risk, Q1

*

 is 6.64 x 10-2 (mg/kg/day)-1

in human equivalents. 

Exposures 

Food and water

HED has determined previously that the cyanamide uses can be considered non- food use 

because: 1) the long history of this compound being used as a fertilizer (likely conversion to 

ammonia and carbon dioxide) at much higher rates and much later in the season and, 2) the 

anticipated total metabolism of the compound and assimilation into components of the general 

carbon pool as demonstrated by metabolism studies. However, if foliar uses are sought in the 

future, the situation will be re-evaluated. Therefore, no dietary assessment was conducted 

previously. No drinking water exposure assessment was conducted either. 

Conclusions: HED registration review scoping team determined that since this is a non food use 

chemical, no dietary exposure from food is expected. However, depending on future drinking 

water assessment from EFED, dietary exposure from water may be possible. As a result, acute 

and chronic dietary assessment for drinking water exposure may be needed. 

Residential 

No residential assessment was conducted previously. 

Conclusions: HED registration review scoping team concluded that, although the Dormex TM 

label does not specify that this is for agriculture use only, based on the purpose of this use (which 

is to promote uniform bud breaks in fruit trees), it is very unlikely that this product will be used 

in residential settings. Therefore, no residential exposure is expected. HED concluded that no 

residential assessment is needed for the Registration Review of cyanamide. HED recommends 

that a statement such as “Do not use in residential settings” be put on the current label 

under directions for use. 

Aggregate 

No aggregate risk assessment was conducted before. 

Page 43 of 51 
Conclusions: HED’s scoping team concurs with previous decision that an aggregate risk 

assessment is not needed for Registration Review of cyanamide. 

Incident Report 

An updated incident report is being prepared by HED. 

Conclusions: HED’s scoping team recommends that an updated incident report is available and 

no further action is needed. 

Occupational Exposure and Risk

Summary of Occupational Use Patterns, Formulations, and Application Rates for 

Hydrogen Cyanamide. 

Formulation Type Application 

Equipment 

Use Sites Maximum 

application rates

(lbs ai/A)

Maximum 

Spray dilution 

(lbs ai/gallon)

Liquid Concentrate Airblast 

Ground boom Orchards 34.4 0.17 

Based on the label uses, the major handler scenarios that are expected to result in the highest 

exposure are mixer/loader and airblast applicator. 

In the most recent comprehensive risk assessment (06/12/2001), occupational handler 

assessments were based primarily on surrogate unit exposures from the Pesticide Handler 

Exposure Database (PHED) as presented in the PHED Surrogate Exposure Guide. The risk 

calculations were based on the maximum application rates and assuming treating 40 acres per 

day. Handler's exposure and risk were calculated at three levels of mitigation: baseline (long 

pants, a long-sleeved shirt, no chemical-resistant gloves, and no respirator), personal protective 

equipment (baseline clothing, additional layer of clothing, chemical resistant gloves and a 

respirator), and engineering controls (baseline clothing, closed tractor cabs and closed 

mixing/loading/transfer systems, and no respirators). The handler scenarios assessed are 

mixer/loader and airblast applicator. Inhalation doses/NOAELs were obtained by converting the 

ACGIH TWA TLV of 0.002 mg/L into mg/kg/day assuming that the breathing rate for 

mixer/loaders is 1.0 m3

/hour, while the breathing rate for the applicator is 0.5 m3/hour. An 

exposure duration of 8 hour/day is assumed. 

For the PPE and engineering control level, the applicator has the higher calculated exposure of 

the two scenarios. Short-term dermal MOEs calculated for handlers ranged from 0.7 to 15 at the 

baseline level, 9 to 310 at the PPE level, and from 100 to 620 at the engineering control level 

(target MOE ≥ 300). Intermediate-term dermal MOEs calculated for handlers ranged from 0.17 

to 4 at the baseline level, 2 to 78 at the PPE level, and from 26 to 150 at the engineering level 

(target MOE ≥ 300). The cancer risk was calculated at 1.4E-04 at the engineering control level. 

A summery of previously calculated MOEs is in Appendix B. 

No major postapplication activities are anticipated. No post application assessment is needed. 

Page 44 of 51 
Conclusions: HED’s scoping team concluded that due to the need for reevaluating the inhalation 

endpoint and the dermal absorption factor (see hazard conclusion above), previously calculated 

MOEs are no longer adequate. A revised occupational risk assessment using the new endpoints 

is needed for Registration Review of cyanamide. 

 

In 2006, the registrant (Degussa Ag) submitted petitions to remove the requirement of closed 

cabs on the Dormex TM label, because the current Dormex TM label requires the use of both a 

full-body chemical-resistant suit and that applicators use an enclosed cab, which is inconsistent 

with the Agency regulation practices. In accordance with 40 CFR Section 170.240 d.5.iv, 

“Persons occupying an enclosed cab shall have all labeling-specified personal protective 

equipment (PPE) immediately available and stored in a chemical -resistant container, such 

as a plastic bag. They shall wear PPE if it is necessary to exit the cab and contact pesticide 

treated surfaces in the treated area. Once PPE is worn in a treated area, it must be removed 

before re-entering the cab”. The registrant had submitted passive dosimetry and urine

biomonitoring data to provide evidence that full-body chemical-resistant suit is equivalent in 

protection to closed cab. HED calculated MOEs and cancer risks using the passive dosimetry 

data, biomonitoring data, and PHED data. Results from the dosimetry study indicate that the use 

of chemical-resistant suits in addition to closed cabs consistently results in approximately 4X 

less exposure to the applicator than open cabs and chemical-resistant suits. Results from the 

biomonitoring studies indicated that closed cab and chemical-resistant suits also resulted in less 

exposure to the applicator than open cabs and chemical-resistant suits; however, the increase in 

protection was very minimal in some cases, while in other cases the level of added protection 

was significantly increased. Results from PHED data indicated that closed cab and chemicalresistant suits also resulted in less exposure to the applicator than open cabs. It was noted that 

there are limitations in the studies and PHED data, which result in these inconsistent study 

results, and difficulty in comparing the effectiveness of using chemical resistant suits and closed 

or open cabs. The overall review of the data indicated that there were risks of concern for the 

applicator. Risk of exposure is lessened by the use of closed-cab, and therefore, HED did not

concur with the registrant’s request to remove the requirement for closed cabs on the label. (HED 

memo of 03/10/06, M. Collantes, D306179). 

The Registrant later submitted additional data and comments for HED to re-evaluate handlers’ 

exposure and cancer risk resulting from the use of airblast application of hydrogen cyanamide to 

grapes and other fruits. The Registrant provided a survey of Dormex users to determine a more 

accurate appraisal of the exposure scenarios (i.e. maximum application rates typically used by 

growers; number of acres typically treated, days of use per year). The registrant also suggested 

the use of central tendency statistics for unit exposure, use of an 80 - 95% clothing protection 

factor versus HED’s default clothing protection factor of 50%, and the use of a different dermal 

endpoint for risk assessment. In response, HED refined applicator MOEs and cancer risk by 

reducing the number of acres treated, reducing the application rate for orchard crops to a 

maximum rate of 17.2 pounds of active ingredient per acre; reducing the number of days 

applicators treat crops per year to 10 for cancer risk, and by incorporating geometric mean values 

in the place of arithmetic means for estimating exposure. HED does not concur with the 

registrant’s request to consider incorporating the use of an 80 to 95 percent clothing protection 

factor. In addition, HED continues to conclude that the 5 mg/kg/day dose level from the rat 

Page 45 of 51 
developmental study is a LOAEL. Therefore, the LOC for applicators using hydrogen 

cyanamide is a margin of exposure greater than 300. Despite incorporation of the above 

mentioned refinements to applicator scenarios using open and closed cabs with personal 

protective clothing, the majority of margins of exposure and cancer risk using open cabs still 

resulted in MOEs of concern (i.e., MOE <300) and cancer risks greater than 1 x10-4 (HED memo 

of 02/09/07, M. Collantes, D333780). 

Cumulative 

The only chemical related to hydrogen cyanamide is calcium cyanamide which is rapidly and 

quantitatively converted to hydrogen cyanamide at the low pH found in the gut. 

Conclusions/Future Actions Needed 

In conclusion, a reevaluation of the inhalation endpoint and dermal absorption factor is needed 

for the Registration Review of cyanamide. A revised occupational risk assessment using the new 

endpoints is needed for Registration Review of cyanamide. 

Data Requirements 

HED recommends that a statement such as “Do not use in residential settings” be put on the 

current label under directions for use. 

References 

1) Bibliography for Cyanamide (OPPIN database); 

2) HED memo of 5/23/01, S. Weiss, D275076; 

3) HED memo of 06/12/01, J. Whalan, D271362; 

4) HED memo of 03/10/06, M. Collantes, D306179; 

5) HED memo of 02/09/07, M. Collantes, D333780; 

6) HED memo of 04/27/01, J. Blondell, D274472; 

7) HED memo of 3/27/00, J. Herndon, D234173 and D240030; 

8) HED memo of 9/2/93; G.Herndon; D185533; 

9) Acta pharmacol. Et toxicol. 1952, 8, 329-337. “The Antabuse effects of some Compunds 

Related to antabuse and Cyanamide”, by J. Hald, E. Jacobsen, and V. Larsen; 

10) Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th Edition. 

ACGIH. Publication 0206. [MRID No. 45315601]. 

Page 46 of 51 
Appendix A 

Summary of Previously Selected toxicological Endpoints for Hydrogen 

Cyanamide (From HED memo of 06/12/01, J. Whalan, D271362). 

Reevaluation 

Needed 

EXPOSURE 

SCENARIO 

DOSE 

(mg a.i./kg/day) 

STUDY and ENDPOINT 

Acute Dietary 

Chronic Dietary 

Acute and chronic Reference Doses (RfDs) are not 

required based on current and anticipated use patterns. 

No 

Incidental Oral, 

Short-Term 

Incidental Oral, 

Intermediate-Term 

Incidental oral endpoints are not required based on 

current and anticipated use patterns. 

No 

Dermal, 

Short-Term 

LOAEL = 5 Developmental toxicity in rats -

Decreased dam body weight gain. 

Target MOE = 300 a

No 

Dermal, 

Intermediate-Long 

term 

LOAEL = 1.25 Reproductive toxicity in rats -

Decreased F1 and F2 pup 

viability. 

Target MOE = 300

No 

Dermal, 

Absorption rate 

11% a The 11% value is based on the 

high-dose of 10 mg (800μg/cm2). 

At low- and mid-dose rates of 0.1 

and 1.0 mg (8 and 80 μg/cm2) the 

dermal absorption rate is 1.79 and 

2.84%, respectively. Assuming a 

body surface area of 18,150 cm2

(mean surface area of adult 

males/females) and daily exposure 

of 26.1 mg ai (based on airblast 

applicator using engineering 

controls at 34.4 lb ai/acre), the 

applied dose to the skin would be 

approximately 1.44 μg/cm2

. 

Yes 

Inhalation, 

(All Exposure 

Durations) 

TLV = 0.002 

mg a.i./L 

ACGIH 8-hour TWA TLV Yes 

Page 47 of 51 
Page 48 of 51 

Cancer Risk Drinking water carcinogenicity in 

mice 

Group C - Possible Human 

Carcinogen based on ovarian 

tumors in CD-1 mice. 

Q1* = 6.64 x 10-2 (mg/kg/day) -1

in human equivalents using a 

mg/kg body weight3⁄4/day 

interspecies scaling factor. 

No 

a

 Since an oral LOAEL was identified for calculating dermal risk, the dermal absorption factor 

used in a route extrapolation should be selected based on similar rat and human dermal doses: 

Rat Dermal Dose (μg/cm2

) Rat Dermal Absorption Factor 

8 1.79% 

80 2.84% 

800 11.1% 
Page 49 of 51 

Appendix B 

 Occupational Handler's Non-cancer and Cancer Risk Summary (From HED memo of 5/23/01, S. Weiss, D

Baseline PPE E

Non-Cancer Risk (MOEs) Non-Cancer Risk (MOEs) Non-Can

Dermal Inhalation Dermal Inhalation Derma

Exposure Scenario 

Application 

Rate 

(lb ai/acre) 

Shortterm Interm ediateterm (all durations) 

Cancer 

Risk 

Shortterm Interm ediateterm (all durations) 

Cancer 

Risk 

Shortterm I

e

Mixer/Loader 

12.9 1.8 0.46 26 6.4e-03 310 78 260 4.0e-05 620 17.2 1.4 0.34 20 8.6e-03 230 58 195 5.3e-05 460 

Mixing/ Loading Liquids for Airblast Application 34.4 0.7 0.17 10 1.7e-02 120 29 98 1.1e-04 230 

Applicator 

12.9 15 4 3 8.9e-04 24 6 34 5.0e-04 280 17.2 11 3 3 1.2e-03 18 5 26 6.6e-04 210 

Airblast Application 

34.4 6 1 1 2.4e-03 9 2 13 1.3e-03 100 

Exposure Levels: Baseline = long pants, a long-sleeved shirt, no chemical-resistant gloves, and no respirator. PPE = Baseline clothing plus an additional layer of clothing, chemical-resistant gloves, and a respirator. Engineering controls = Baseline clothing, closed tractor cabs and closed mixing/loading/transfer systems, and nTarget Dermal MOE ≥ 300 Target Inhalation MOE ≥ 1 Target Cancer Risk ≤ 1.0E-6 
Page 50 of 51 

V. GLOSSARY OF TERMS AND ABBREVIATIONS 

ai Active Ingredient 

ACGIH American Conference of Governmental Industrial Hygienists 

aPAD Acute Population Adjusted Dose 

AR Anticipated Residue 

CFR Code of Federal Regulations 

cPAD Chronic Population Adjusted Dose 

CSF Confidential Statement of Formula 

DCI Data Call-In 

DFR Dislodgeable Foliar Residue 

DWLOC Drinking Water Level of Comparison. 

EC50 50% Effect Concentration 

ECOTOX An EPA database for locating chemical toxicity data for aquatic life, 

terrestrial plants and wildlife

EDWC Estimated Drinking Water Concentration 

EEC Estimated Environmental Concentration 

EFSA European Food Safety Authority 

EPA Environmental Protection Agency 

EUP End-Use Product 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FQPA Food Quality Protection Act 

FOB Functional Observation Battery 

FWP Final Work Plan 

GENEEC Tier I Surface Water Computer Model 

GLN Guideline Number 

HIARC Hazard Identification Assessment Review Committee

IR Index Reservoir 

LC50 Median Lethal Concentration. A statistically derived concentration of a 

substance that can be expected to cause death in 50% of test animals. It is 

usually expressed as the weight of substance per weight or volume of 

water, air or feed, e.g., mg/l, mg/kg or ppm. 

LD50 Median Lethal Dose. A statistically derived single dose that can be 

expected to cause death in 50% of the test animals when administered by 

the route indicated (oral, dermal, inhalation). It is expressed as a weight of 

substance per unit weight of animal, e.g., mg/kg. 

LOC Level of Concern 

LOAEL Lowest Observed Adverse Effect Level 

LOEC Lowest Observed Effect Concentration 

mg/kg/day Milligram Per Kilogram Per Day 

mg/L Milligrams Per Liter 
Page 51 of 51 

MOE Margin of Exposure 

MRID Master Record Identification (number). EPA's system of recording and 

tracking studies submitted. 

MRL Maximum Residue Level 

MUP Manufacturing-Use Product 

NA Not Applicable 

NPDES National Pollutant Discharge Elimination System 

NR Not Required 

NOAEC No Observed Adverse Effect Concentration 

NOAEL No Observed Adverse Effect Level 

NOEC No Observed Effect Concentration 

OPP EPA Office of Pesticide Programs 

OPPTS EPA Office of Prevention, Pesticides and Toxic Substances 

OSHA Occupational Safety and Health Administration 

PAD Population Adjusted Dose 

PCA Percent Crop Area 

PDP USDA Pesticide Data Program 

PHED Pesticide Handler's Exposure Data 

ppb Parts Per Billion 

PPE Personal Protective Equipment 

ppm Parts Per Million 

PRZM/EXAMS Tier II Surface Water Computer Model 

PWP Preliminary Work Plan 

Q1* The Carcinogenic Potential of a Compound, Quantified by the EPA's 

Cancer Risk Model 

REI Restricted Entry Interval 

RfD Reference Dose 

RQ Risk Quotient 

SAP Science Advisory Panel 

SF Safety Factor 

SLN Special Local Need (Registrations under Section 24(c) of FIFRA) 

TGAI Technical Grade Active Ingredient 

TLV Threshold Limit Value 

TREX Terrestrial Residue EXposure model 

TWA Time Weighted Average 

USDA United States Department of Agriculture 

UF Uncertainty Factor 

WPS Worker Protection Standard