### TABLE OF CONTENTS

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

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

III. ECOLOGICAL RISK ASSESS MENT PROBLEM FORMULATION ............ 10

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

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

Page 2 of 51I. PRELIMINARY WORK PLAN

Introduction:

The Food Quality Protection Act of 1996 manda ted a new program: registration review. All pesticides distributed or sold in the United Stat es 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 pr oduct labeling. The new registration review program is intended to make sure that, as the ab ility to assess risk evolves and as policies and practices change, all registered pesticides co ntinue to meet the st atutory standard of no unreasonable adverse effects. Changes in science, public policy, and pesticide use practices will occur over time. Through the new registrati on 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/oppsrr d1/registration_review/

.

The Agency has begun to implement the new registration review program, and will review each registered pesticide every 15 years to determine wh ether it continues to m eet the FIFRA standard for registration. The public phase of registration review begins wh en the initial docket is opened for each case. The docket is the Agency’s opportun ity 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. Afte r reviewing and responding to co mments and data received in the docket during this in itial comment period, the Agency will develop and commit to a final work plan and schedule for the regist ration review of hydrogen cyanamide.

Hydrogen cyanamide is a plant grow th regulator used to promote uniform bud break in fruit trees and vines. Hydrogen cyanamide was first register ed 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 comprehe nsive human health and ecological risk assessments, including an endangered species as sessment for all uses of hydrogen cyanamide.

Ecological Risk:

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

There is also concern for indir ect effects on listed species.

• Preliminary review of Tier I pl ant toxicity studies indicate insufficient data on terrestrial plant toxicity for completion of the ecologi cal assessment, so the Agency anticipates requiring Tier II vegetative vigor and seedling emergence studies.

• The Agency does not anticipate addi tional 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 lis ted threatened or endangered species (listed species) or their desi gnated critical habitat. If the screening level assessment indicates that hydrogen cyan amide “may affect” a listed species or its

Page 3 of 51designated 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 habi tat. 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-f ood use chemical, so dietary exposure from food is not expected although th ere is the potential for expos ure from drinking water. Therefore, the Agency plans to comple te a drinking water assessment for hydrogen cyanamide.

• The inhalation endpoint and dermal absorpti on 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 timelin e 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 subm ission 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 51Guidance for Commenters: The public is invited to comme nt on EPA’s preliminary regist ration review work plan and rationale. The Agency will carefully consid er 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 Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade irritant issues resulting from lack of Maximum Residue Levels (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the na ture of the concern. There are no U.S. tolerances for hydrogen cyan amide, 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 O PP’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 qua ntitatively or qualitatively in pesticide risk

assessments.

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to hydrogen cyan amide, 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 prov ide information and data that will assist the Agency in refining the human health and ecolo gical 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 relate d to mass per unit area of treatment zone

e. frequency of application, applicati on 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 513. Use history.

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

5. Application timing (date of firs t 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 90 th percentile number of applications – county

d. total pounds per year – county

e. the year the pesticide was last us ed 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, rept ilian, amphibian and mammalian mortalities) not al ready reported to the Agency.

12. Monitoring data.

Next Steps: After the comment period closes, the Agency w ill review the comments received, and then issue a Final Work Plan for this pesticide.

Page 6 of 51II. FACT SHEET

Background Information :

• Hydrogen cyanamide Registrati on Review Case Number: 7005

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

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

Trees and Plants LLC

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

• No food uses or tolerances.

• Special Review and Reregist ration Division (SRRD), Chemi cal 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 regula tor used to promote uniform bud break in

fruit trees and vines.

• Based on the rapid metabolism of this chemical , residues are not expect ed at harvest. The Agency determined in 2000, all registered uses can be considered non-food uses.

• Hydrogen cyanamide is currently register ed 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 (Calif ornia only), peaches, and nectarines.

• Hydrogen cyanamide is formulated as a sol uble concentrate and ma y be applied using airblast or backpack sprayers.

• Hydrogen cyanamide is not registered for residential use.

Recent Actions:

• The most recent and comprehensive human h ealth 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) regist rations that added uses including apple, blueberry, cherry, peach, and nectarine.

• Duomax, EPA Reg. No. 84374-R, is a pendi ng end-use product, submitted in 2007. If approved, the registration would allow use on a pples, 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, th e risks of concern are primarily related to direct effects on aquatic species and non-target terrestrial plan ts. There is also concern

for indirect effect s on listed species.

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

invertebrates.

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

concentrations.

• The Agency does not foresee requiring any additi onal environmental fate studies listed in CFR Part 158 prior to conducti ng the planned assessments.

• Preliminary review of Tier I pl ant toxicity studies indicate insufficient data on terrestrial plant toxicity for completion of the ecologi cal 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 specifi c use information as well as monitoring data.

These needs are outlined in S ection 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 anticip ated risk assessment needs for human health. The following is a summary of those anticipated needs:

• The toxicological database for hydrogen cy anamide 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 wate r exposure and risk a ssessment for existing outdoor uses of hydrogen cyanamide. As the Ag ency 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 reside ntial uses of hydrogen cyanamid e; therefore, no residential

risk assessment is needed.

Occupational :

• The inhalation endpoint and the dermal absorpti on factor need to be re-evaluated, thus, the MOEs in the previous occupational risk assessment may no longer be adequate. A revised occupational risk a ssessment using newly selected endpoints is needed.

• The Agency anticipates revising the human health assessment.

Page 8 of 51Incidents:

• The Agency received two ecological incident reports for cyanamide, both citing damage to crops. Defoliation of lemon trees was re ported in 1993 in conjunction with spray drift that had allegedly resulted from an applica tion to grapes made dur ing stormy weather. Kiwi vine damage was reported in 2001, alle gedly 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 Ameri can Association of Poison Control Center (AAPCC) data or the OPP Inci dent 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 a nd 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 51III. ECOLOGICAL RISK ASSESS MENT PROBLEM FORMULATION

Page 10 of 51

### Registration Review

Ecological Risk Assessment
Problem Formulation for:

Cyanamide

H 2 

### N-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 51STRESSOR SOURCE AN D 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 th e following crops: blackberries in Georgia (GA03000600), figs in California (CA0400020 0) and grapes in Hawaii (HI03000300). Hydrogen cyanamide is applied as a single airb last or backpack spray to the plant buds approximately 30 days before bud break to synchronize blossoming a nd/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 51INTEGRATION 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 EC 50 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 (est uarine invertebrate) exposed to hydrogen cyanamide was 6.3 ppm ai, which classifies this compound as mode rately toxic to Mysidops is 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 fre shwater fish) the 96-hour LC50 is 46 ppm ai (MRID 073728). These results classify cy anamide as slightly toxic to fish.

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

indicated an LC50 of 1.93 millimol ar, or 81.25 ppm ai, which classifies cyanamide as slightly toxic to fish. The European Food Safety Ag ency (EFSA, 2006) has al so 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 51Aquatic Toxicty, Chronic

.

Guideline data (MRID 44076702) indicate that Cyan amide (50% ai) is highly toxic to daphnid growth and reproduction of young. The most sens itive 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 emerge nce, 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 reproducti on, NOEC:<0.507 ppm for growth effects and 2.03 ppm for reproduction. Parameters affected incl uded weight, length, days to hatch, days to swimup, hatch survival. This study was rate d 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 de termined 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 greate r 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 F ood 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 51A two-generation rate reproduc tion study established a NOEL of 25 ppm or 1.25 mg/kg/day. The endpoints affected were decreases in ma ternal body weight gain and decreased food consumption.

Terrestrial Invertebrates

An acute contact toxicity st udy (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 re sults are expressed as EC50 (50% effective concentration). Under USEPA guidelines, the re sults 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 seedli ng emergence endpoint. Allium cepa (onion) was the most sensitive plant, with an EC 50 value of 0.79 lb ai/acre for cyanamide applied directly to

the soil.

Page 16 of 51Table 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 EC 50 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 appl ication of cyanamide to grapes made during stormy weather allegedly resulted in spray drift that caused defo liation of lemon trees in several nearby groves (I000423-001). In 20 01, 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 adve rse field effects to animals that have been attributed to the use of cyanamide. The Agen cy 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 51EXPOSURE CHARACTERISTICS

The available environmental fate data for hydrogen cy anamide 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 degradati on processes (hydrolysis and phot olysis) 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, gua nylurea, 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 atmm 3 /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 Aqueousphotolysis halflife 29 days in pH 5 and pH 7 buffers

at 25 o 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 ECOSYS TEMS POTENTIALLY AT RISK

For cyanamide and pesticides in general, the ecosy stems at risk are those in close proximity to the use areas. These would include agricultural fi elds (orchards and vineyards in this case), surrounding terrestrial hab itats, and water bodies directly adja cent to treated fields that may

receive chemical residues via drift, volatilizat ion, or runoff. Within water bodies, the water column, sediment, and pore water are all compar tments of concern, however, given cyanamide’s solubility it is most likely to be found in the water column.

Page 18 of 51Table 5 gives estimates of the national-level usage of cyanamide. More than half of the usage was on grapes, followed by cherries, blueberries, ki wifruit, apples, figs, and prunes/plums. All reported use for figs and kiwifruit was from Calif ornia; these crops are re gistered 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 cont inental 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 reflec t population sustainabi lity 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 regi stered uses for Cyanamide but no usage has been observed in our usage databases.

Page 19 of 51Figure 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 51Blackberries, 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 51Tame blueberries ha rvested, 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 51Cherries, 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 51Figs, 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 51Grapes, 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 51Kiwifruit, 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 51Nectarines, total acres, 1997

Legend

(acres)

1.0-3.0

3.0-9.0

9.0-30.0

30.0-116.0

Page 27 of 51Peaches, 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 51ASSESSMENT ENDPOINTS

Assessment endpoints are defined as “explicit expressions of the actual envir onmental value that is to be protected.” Defining an assessment e ndpoint involves two steps: 1) identifying the

valued attributes of th e 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 attr ibutes (i.e., survival and reproduc tion). Therefore, selection of the assessment endpoints is based on valued entit ies (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 cont amination. The selection of clearly defined assessment endpoints is important because they provide direction and bou ndaries in the risk assessment for addressing risk management issues of concern. Changes to assessment endpoints are typically estimated from the available toxici ty studies, which are used as the measures of effects to characterize potential ec ological risks associated with e xposure to a pesticide, such as cyanamide.

To estimate exposure concentra tions, the ecological risk as sessment considers a single application at the maximum application rate to fields that have vulnerable soils. The most sensitive toxicity endpoints are used from surroga te 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 invertebrate s, and plants. These te sts include short-term acute, sub-acute, and reproduction st udies 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 pesticid e to cause adverse effect s, to determine whether further testing is required, and to determine th e need for precautionary label statements to minimize the potential adverse effect s to non-target animals and plants.

Data on the toxicity of cyanamide to aquatic a nd terrestrial plants has been submitted to the Agency, but has not yet been reviewed for valid ity. However, given the registered use of cyanamide as a plant growth regulator, and warni ngs on the label regarding leaf loss and blossom loss in adjacent crops, adverse eff ects on terrestrial plants are expect ed to be a major focus of the

risk assessment.

In terms of direct effects to terrestrial plants, bo th 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 s hoot dry weight, as measured during a seedling emergence test, as the most sensitive endpoint (NOEC = 0.092 lbs. a.i./A, EC 25 = 2.80 lbs. a.i./A). Onion was the most sensitive monocot, with an EC 50 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 expos ure occur, listed spec ies in all taxa may potentially be affected indirectly due to alterations in their hab itat (e.g., food sources, shelter, and areas to reproduce).

Page 29 of 51Because 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). Le af loss has been noted in lemon trees exposed to cyanamide. A spray drift buffer to prevent adverse effects in plants wi ll need to be calculated.

Based on a preliminary analysis of exposure, ther e may be a concern for di rect, acute and chronic effects in freshwater invertebrates. This may in turn have indirect effects on consumers of invertebrates such as fish and amphibian s 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 c oncentrations. An exposure pathway is the means by which a pesticide

moves in the environment from a source to an ecological receptor. Fo r 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 r eceptors, 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 hydrog en cyanamide action area. For terrestrial organisms, the major route of exposure consider ed 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 a nd dermal exposure may also be important exposure routes, as cyanamide is known to be irritating to the eyes, sk in, and respiratory tract. For aquatic animal species, the major routes of exposure are considered to be via the respirat ory surface (gills) or the integument. Direct contact and/ or root uptake is the major rout e of exposure for terrestrial and wetland (riparian) plants, while aquatic plants ma y be exposed via direct uptake and adsorption. Estimated exposure concentrations for all orga nisms 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 conceptu al model was developed that represents the possible relationships betw een the stressor, ecological receptors, and the assessment endpoints. The major transport path ways for hydrogen cyanamide are spray drift and run-off, resulting in exposure to various terr estrial and aquatic receptors. The Agency has received only two ecological incide nt reports for cyanamide. Both incidents involved damage to crops. The Agency has received no report of any adverse field effe cts to animals that have been attributed to the use of cyanamide. The Agen cy also has received no incident report from pesticide registrants concerning cyanamide cont amination 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 plan ts. Additionally, there is concern for indirect effects on listed species.

Page 30 of 51Figure 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”) (Janua ry 2004), and will be done in

accordance with Section 7 of the Endangered Species Act.

Previously completed screening level risk asse ssments 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 base d on effects to aquatic ecosystems, but need to

be revisited based on effects data for both aquatic species and terr estrial plants, and quantitative exposure estimates. Finally, analysis of potentia l indirect effects on lis ted species is required.

The Agency wishes to better understand the pot ential 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 pr evious assessments were based on different

Page 31 of 51assumptions that may affect the re sulting RQ values. In addition to refining the terrestrial plant risk assessment, other uncertainties and pot ential 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 require d. 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 emergen ce 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 EC 50 . It is EFED policy to eval uate risks to plants using

the NOAEL/NOAEC and the EC 25. The raw data from the Tier II study would be needed in order to calculate the ap propriate endpoint (EC 25 ). 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: Vegetati ve Vigor Limit Test: Final Report: Lab Project Number: 7042087: 851-002. Unpublis hed study prepared by Institut fur Biologische Analytik und Consultin g 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 un d Consulting IBACON GmbH. 89 p. {OPPTS 850.4100}

y 45382201 Hertl, J. (2000) Toxicity of SK W Cyanamide L 500 to Anabaena flosaquae in an Algal Growth Inhibition Test: Final Report: Lab Project Number: 6677210. Unpublished study prepared by Instit ut fur Biologische Analytik und Consulting IBACON GmbH. 78 p.

y 45382202 Volkl, S. (2000) (Carbon 14)-Cyanami de 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 capri cornutum) 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 Te st: Final Report: Lab Project Number: 6679240. Unpublished study prepared by Instit ut fur Biologische Analytik und Consulting IBACON GmbH. 76 p. {OPPTS 850.4400}

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

and chronic risk to invertebrates. Tier two modeling (PRZM/EXMS) will be conducted to refine the aquatic expected envi ronmental concentrations (EECs).

y Cyanamide is mobile and not expected to be pers istent in water. Ther efore, chronic exposure

to organisms that inhabit the water column would require repeat ed 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 trou t (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 stat istically determined and the study should therefore fulfill the guideline. After consideration of the i ssue by the EFED Aquatic Biology Technical Team, a NOEAC value was estima ted and accepted by EFED (Memo, October 8, 1999). A NOAEC of 0.8 ppm for ra inbow trout will be used to evaluate the effects of chronic exposure to freshwater fish. The re sults of a long-term exposure study with the midge were included in the EFSA (2006) re port 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 an imals will be assumed to be as sensitivite to cyanamide as freshwater species. It is possi ble that this assumption will underestimate risk and this uncertainty can only be allievated by ch ronic toxicity data for saltwater species. There are very few chemical compounds with a si milar structure or mode of action. In some cases, EFED uses toxicity data from similar co mpounds to estimate the relative sensitivity of freshwater and saltwater species. Because ther e 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 i ndicating 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 be tween the edge of the application area and any water bodies to protect w ildlife and plants. Using tier II models, PRZM/EXMS, AgDrift, and AgDisp, this buffer will be re-evaluate d. Organisms of concern include aquatic invertebrates and plants. The appropriate buffer to protect each of these taxa will be calculated separately.

Page 33 of 51If the planned ecological risk as sessment indicates that cyanamid e may potentially impact, either directly or indirectly, lis ted species or critical habitat, and therefore does not support a “not likely to adversely affect” determination, further re finements will be made. This will involve determining whether use of cyanamide “may affect” a particular listed spec ies, and if so, whether it is “likely to adversely affect” the species, or in the case of critical habi tat, whether use of the pesticide may destroy or advers ely 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 woul d support a determinati on that cyanamide use will have no effect on the species or critical habi tat. 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 terrest rial plants, the next step for EPA and the Services would be to identify whic h listed species and critical hab itat are potentially implicated. Analytically, the identification of such species and critical hab itat can occur in either of two ways. First, the agencies could determine whethe r the action area overlaps critical habitat or the occupied range of any listed sp ecies. If so, EPA would examine whether cyanamide’s potential impacts on non-endangered species would affect the lis ted species indirectly or directly affect a

constituent element of the critical habitat. Alternatively, the agencies could determine which listed species depend on biological re sources, or have constituent elements that fall into, the taxa that may be directly or indire ctly impacted by cyanamide. Th en 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 additi onal environmental fate studies listed in 40 CFR Part 158 prior to conducting the planned as sessments. However, there is currently insufficient data on terrestrial plant toxicity to co mplete 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 estu arine 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 th at all best available science is utilized. The Agency uses the ECOTOX database as its mechanism for searching the open literature for ecological effects inform ation. ECOTOX integrat es three previously independent databases - AQUI RE, 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 51Terrestrial 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 pres umed. The raw data from the Tier II plant study presented in the EFSA assessment woul d greatly reduce this uncertainty.

Other Information Needs

There is specific information that will assist the Agency in refini ng the ecological risk assessment, including any species-specific effect s determinations. The Agency is very much interested in obtaining the following information:

1. use or potential use distributi on (e.g., acreage and geographica l distribution of relevant crops)

2. use history

3. median and 90 th 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 da ta (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 90 th percentile number of applications – county

d. total pounds per year – county

e. the year the pesticide was last us ed 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 alr eady reported to the Agency

8. monitoring data

The analysis plan will be revi sited and may be revised dependi ng 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 51Table 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 51Crop 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 51IV. HUMAN HEALTH EFFECTS SCOPING DOCUMENT

Page 38 of 51OSHA’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 base d on human data, and that the sensitive population was worker who consume ethanol, therefore, the target MOE fo r inhalation was set at 1. Cyanamide was classified as a Group C ch emical–a possible human carcinogen, based upon female mouse ovarian granulosa-theca tumor ra tes. 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 base d on human data, and that the sensitive population subgroup was workers who consume et hanol, 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 ra tes. 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 engi neering control level (target MOE ≥ 300). The cancer risk

was calculated at 1.4E-04 at th e engineering control level.

HED’s scoping conclusions are: 1) the toxicity da ta 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 ri sk from drinking water exposure. For dermal endpoints, although the endpoints are ad equate, 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/m 3 ) TLV is not based on human toxicity da ta 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 (t etramethylthiuram disulfide). Since a TLV-TWA of 1.0 mg/m 3 was recommended for thiram by ACGIH, therefore, ACGIH recommended a 2 mg/m 3 for cyanamide. Based on the cyanamide ra t 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/m 3 for cyanamide (= 0.23 mg/kg/day assuming 8 hour per day at the breathing rate of 1.0 m 3 /hour), and therefore, the 2 mg/m 3 is less protective. A re-selection of the inhalation endpoint is needed for the Regi stration Review of cyan amide; 2) depending on future drinking water assessment from EFED, acute and chronic dietary assessments for drinking water exposure may be needed; 3) no resident ial 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 fa ctor as discussed above, the MOEs in the previous occupational risk assessment are no l onger adequate. A revi sed occupational risk assessment using newly selected endpoints is ne eded for the Registration Review of cyanamide.

Page 40 of 51Introduction

HED has evaluated the status of the human h ealth 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 consid ered 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 da tabase, and Google online search.

Hydrogen cyanamide is a plant growth regulato r used to promote uniform bud break in fruit trees. Hydrogen cyanamide currently has a Sect ion 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/acr e, and apples, cherries, kiwis at 34.4 lb ai/acre (Dormex TM , EPA Reg. No. 54555-2). It has been de termined 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 co mbustible and deliquescent. The formulated product is the material tested in all toxicity studies.

Table 1. Cyanamide Nomenclature

Chemical structure 

### NH 2 

### N

Common name Cyanamide Empirical formula CH 2 N 2 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 patte rn, 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 th e corrosive nature of cyanamide.

Effects observed in subchronic and chronic t oxicities include decrea sed body weight gain, tremors, salivation, decreased T 4 , increased relative thyroid-pa rathyroid weights, and urinary bladder and kidney lesions. Deve lopmental effects were observed in rats (increased resorptions, decreased fetal body weight, increase in diaphragma tic hernias, and wavy/bent ribs) and rabbits (increased early resorptions and dead fetuses, de crease in fetal weight and size, an increase in

Page 41 of 51small 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 cau sed maternal effects. There are no reproductive toxicity concerns as the reproductive NOAEL is 12-fo ld greater than the parental NOAEL. Hydrogen cyanamide was classified as a Group C chemical–a possible human carcinogen, based upon female mouse ovarian gr anulosa-theca tumor rates in a 104-week drinking water study. The unit risk, Q 1 * 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 tremor s 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, includ ing miosis, excessive salivation, tearing, and twitching, is mentioned in the literature. The only suggestions of

endocrine effects in the da ta base were decreased T 4 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) Th reshold Limit Value (TLV). The HIARC chose to adopt the TLV–currently 0.002 mg/L–for calculatin g worker inhalation risk because HIARC considered it being prot ective of hydrogen cyanam ide’s irritancy and

Antabuse-effect. The HIARC believed that th e 0.002 mg/L TLV concen tration is based on human data, and that the sensit ive population is known–workers that consume ethanol–and the TLV protects workers from the Antabuse-effect, ther efore, the target MOE for inhalation was set

at 1.

A summary of the toxicological endpoint decisions from the mo st 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 curren t policies. The scoping team concluded that the toxicity data base is complete. Howeve r, the endpoint selections may not be adequate

. No dietary endpoints were selected before. Depending on a futu re 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 fact or was based on 10 mg dosing (or 800 μ g/cm 2 ) which is very high dosing level compared to expected human exposure levels based on maximum label use rate (roughly 1.44 μg/cm 2 ), there fore, the 11% dermal ab sorption previously selected is overly conservative, as cyanamide is a strong de rmal 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 i nhalation endpoint, the 0.002 mg/L (=2 mg/m 3 ) 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 disulf ide). Since a TLV-TWA of 1.0 mg/m 3 was recommended for

Page 42 of 51Thiram by ACGIH (based on relative potential to cause irritation when compared with other irritants), therefore, ACGIH recommended a 2 mg/m 3 for cyanamide. Based on the cited rabbit study, if the uncertainty factor of 1000 is a dded 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 th e ACGIH recommended TLV of 2 mg/m 3 for cyanamide (= 0.23 mg/kg/day assuming 8 hour per da y at the breathing rate of 1.0 m 3 /hour), and therefore, the 2 mg/m 3 is more protective. However, if the rat developmental study was considered, the dose for regulation based on developmental eff ects is 0.017 mg/kg/day which is lower than 0.23 mg/kg/day (= TLV of 2 mg/m 3 ). A re-selection of the inhalation endpoint is needed for the Registration Review of cyanamide. HED’s re gistration review scoping team concurs with previous decision on cancer cl assification where hydrogen cyanam ide 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, Q 1 * is 6.64 x 10 -2 (mg/kg/day) -1
in human equivalents.

Exposures

Food and water HED has determined previously that the cyan amide uses can be considered non- food use because: 1) the long history of this compound bei ng used as a fertilizer (likely conversion to ammonia and carbon dioxide) at much higher rate s and much later in the season and, 2) the anticipated total metabolism of the compound and assimilation into com ponents 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 expos ure 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 dr inking water exposure may be needed.

Residential No residential assessment was conducted previously.

Conclusions: HED registration review scoping te am 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 resident ial exposure is expected. HED concluded that no

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

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

under directions for use.

Aggregate

No aggregate risk assessment was conducted before.

Page 43 of 51Conclusions: 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 exp ected to result in the highest exposure are mixer/loader a nd airblast applicator.

In the most recent comprehensive risk a ssessment (06/12/2001), occupational handler assessments were based primarily on surrogate unit exposures from the Pesticide Handler Exposure Database (PHED) as presented in th e 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 cal culated at three levels of mitigation: baseline (long pants, a long-sleeved shirt, no chemi cal-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 respir ators). The handler scenarios assessed are mixer/loader and airblast app licator. Inhalation doses/NOAELs were obtained by converting the ACGIH TWA TLV of 0.002 mg/L into mg/kg/da y assuming that the breathing rate for

mixer/loaders is 1.0 m 3 /hour, while the breathing rate for the applicator is 0.5 m 3 /hour. An exposure duration of 8 hour/day is assumed.

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

the two scenarios. Short-term dermal MOEs cal culated 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 en gineering control level. A summery of previously calcula ted MOEs is in Appendix B.

No major postapplication activities are anticipate d. No post application assessment is needed.

Page 44 of 51Conclusions: HED’s scoping team concluded that due to the need for reevaluating the inhalation endpoint and the dermal absorption factor (see ha zard conclusion above), previously calculated MOEs are no longer adequate. A revised occu pational risk assessment using the new endpoints is needed for Registration Review of cyanamide.

In 2006, the registrant (Degussa Ag) submitted pet itions 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 enclos ed 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 su it is equivalent in protection to closed cab. HED calculated MOEs and cancer risk s 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 resu lts in approximately 4X less exposure to the applicator than open cabs an d chemical-resistant suits. Results from the biomonitoring studies indicated that closed cab and chemical-resistan t suits also resulted in less exposure to the applicator than open cabs and chem ical-resistant suits; ho wever, the increase in protection was very minimal in some cases, whil e in other cases the le vel of added protection was significantly increased. Resu lts 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 effectiven ess of using chemical re sistant suits and closed or open cabs. The overall review of the data i ndicated 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 reque st to remove the requirement fo r 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 resulti ng from the use of airblast app lication of hydrogen cyanamide to grapes and other fruits. The Regi strant provided a survey of Do rmex users to determine a more accurate appraisal of the exposur e scenarios (i.e. maximum applic ation 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 ex posure, use of an 80 - 95% clothing protection

factor versus HED’s default clothi ng protection factor of 50%, a nd the use of a different dermal endpoint for risk assessment. In response, HE D refined applicator MOEs and cancer risk by reducing the number of acres tr eated, 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 incor porating geometric mean values in the place of arithmetic means for estimati ng 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 51developmental study is a LOAEL. Therefor e, the LOC for applicators using hydrogen cyanamide is a margin of exposure greater th an 300. Despite incor poration of the above mentioned refinements to applicator scenario s 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 con cern (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 cyanamid e is calcium cyanamide which is rapidly and quantitatively converted to hydrogen cyanam ide at the low pH found in the gut.

Conclusions/Future Actions Needed

In conclusion, a reevaluation of the inhalation en dpoint and dermal absorption factor is needed for the Registration Review of cyanamide. A re vised occupational risk assessment using the new endpoints is needed for Regist ration 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 Va lues and Biological Exposure Indices, 6 th Edition. ACGIH. Publication 0206. [MRID No. 45315601].

Page 46 of 51Appendix A

Summary of Previously Selected to xicological 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/cm 2 ).

At low- and mid-dose rates of 0.1 and 1.0 mg (8 and 80 μg/cm 2 ) the dermal absorption rate is 1.79 and 2.84%, respectively. Assuming a body surface area of 18,150 cm 2
(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 th e skin would be approximately 1.44 μg/cm 2

. Yes

Inhalation, (All Exposure Durations) TLV = 0.002 mg a.i./L ACGIH 8-hour TWA TLV Yes

Page 47 of 51Page 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 calcula ting dermal risk, the dermal absorption factor used in a route extrapolation s hould be selected based on sim ilar rat and human dermal doses:

Rat Dermal Dose ( μ g/cm 2 ) Rat Dermal Absorption Factor

8 1.79%

80 2.84%

800 11.1%Page 49 of 51Appendix BOccupational Handler's Non-cancer and Cancer Risk Summary(From HED memo of 5/23/01, S. Weiss, D275076)BaselinePPEEngineering ControlsNon-Cancer Risk (MOEs)Non-Cancer Risk (MOEs)Non-Cancer Risk (MOEs)DermalInhalationDermalInhalationDermalInhalationExposureScenarioApplicationRate(lb ai/acre)ShorttermIntermediateterm(alldurations)CancerRiskShorttermIntermediateterm(alldurations)CancerRiskShorttermIntermediateterm(alldurations)CancerRiskMixer/Loader12.91.80.46266.4e-03310782604.0e-056201503762.1e-0517.21.40.34208.6e-03230581955.3e-054601202822.8e-05Mixing/LoadingLiquids forAirblastApplication34.40.70.17101.7e-0212029981.1e-04230581415.5e-05Applicator12.915438.9e-04246345.0e-0428070345.1e-0517.211331.2e-03185266.6e-0421052266.8e-05AirblastApplication34.46112.4e-0392131.3e-0310026131.4e-04Exposure 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 tractorcabs and closed mixing/loading/transfer systems, and no respiratorsTarget Dermal MOE≥300Target Inhalation MOE≥1Target Cancer Risk≤1.0E-6Page 50 of 51 V. GLOSSARY OF TERMS AND ABBREVIATIONS

ai Active Ingredient

ACGIH American Conference of G overnmental 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.

EC 50 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

LC 50 Median Lethal Concentration. A st atistically 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.

LD 50 Median Lethal Dose. A statisti cally derived single dose that can be expected to cause death in 50% of th e test animals when administered by the route indicated (oral, dermal, inhalati on). It is expresse d 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 LiterPage 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, Pe sticides 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 Q 1 * 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 (Registrat ions 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