### TABLE OF CONTENTS

Page #

I. Preliminary Work Plan (PWP)..............................3

II. Fact Sheet.........................................................7

III. Ecological Risk Assessment Pr oblem Formulation......10

IV. Human Health Effects Scoping Document.................26

V. Glossary of Terms and A bbreviations......................32

2I. PRELIMINARY WORK PLAN
Urea Sulfate

Introduction The Food Quality Protection Act of 1996 amendments to the Federal Fungicide Insecticide and Rodenticide Act (FIFRA) manda ted a new program: re gistration review. All pesticides distributed or sold in the United States ge nerally must be registered by the United States Environmental Protection Agency (the Agency) based on scientific data showing that they will not cause unreasonabl e 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 ability to assess and reduce risk evolves and as policies and practices change , all registered pesticides co ntinue to meet the statutory
standard of no unreasonable adverse effects. Changes in science, public policy, and pesticide use practices will occur over ti me. Through the new registration review program, the Agency periodically reevaluates pe sticides to make sure that as change occurs, products in the market place can continue to 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 plans to review each registered pesticide every 15 year s 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 clearly what it knows about the pesticide and wh at additional risk analyses and data or
information it believes are needed to ma ke a registration review decision.

Anticipated Risk Assessment and Data Needs

The Agency anticipates conducting a compre hensive ecological risk assessment which will include an endangered species risk asse ssment. The Agency does not expect to
conduct an additional human health risk assessm ent. At this time, the Agency does not anticipate that additional da ta will be needed.

Ecological Risk

• A screening level ecological risk assessm ent has not been conducted for urea sulfate. Only “hazard assessments” on the agricultural uses of urea sulfate have been completed (1989).

• Urea sulfate rapidly dissociates to urea a nd sulfuric acid and/or sulfate ions. Sulfate ions were not evaluated because they are not expected to pose a significant ecological risk.

• Based on the previously conducted hazard assessments, sulfuric acid resulting from the use of urea sulfate may pose a risk to terrestrial wildlife and also could lower the pH of very small and sha llow water bodies with a low buffering capacity, and therefore may harm aquatic organisms. These issues will be explored further in Registration Review.

• The Environmental Fate and Effects Division (EFED) will use the hazard assessments and the supporting data as a resource for completing an ecological

3risk assessment. The Agency will also consider the 1989 U.S. Fish and Wildlife Service Biological Opinion which discu sses the use of urea sulfate on several vegetables, fruits, a nd nut tree crops.

• The planned ecological risk assessment will allow the Agency to determine
whether urea sulfate’s use has "no effect" or "may affect" federally listed threatened or endangered species (listed species) or their designated critical
habitat. If the assessment indicates that urea sulfate "may affect" a listed species or its designated critical habitat, th e assessment will be refined. The refined assessment will allow the Agency to determine whether use of urea sulfate is “likely to adversely affect” the species or critical habitat or "not 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 National Marine Fisheries Service (the Services), as appropriate.

• The Agency does not foresee requiring a ny additional ecolog ical effects or environmental fate studies prior to conducting the planned assessments. The Agency will however conduct a search of the open literature to ensure that all best available science is utilized. The Agen cy uses the ECOTOX database as its mechanism for searching the open literatur e for ecological effects information. ECOTOX integrates three previously independent databases – AQUIRE, PHYTOTOX, and TERRETOX – into a syst em which includes toxicity data derived predominately from the peer-rev iewed literature, for aquatic life, terrestrial plants, and terrestrial wildlife.

Human Health Risk

• The Agency does not anticipate the need for new dietary and occupational risk
assessments because the risks do not exceed the Agency’s level of concern.

• The Agency does not expect to require additional data for urea sulfate.

• Several product chemistry studies have not been reviewed and will be evaluated later in the process.

4Timeline

EPA has created the following estimated timeline for the completion of the urea sulfate registration review.

Activities Estimated Completion Phase 1: Opening the docket
Open Public Comment Period for Urea Sulfate Docket Aug. 2007

Close Public Comment Period Nov. 2007 Phase 2: Case Development
Develop Final Work Plan (FWP) Jan. 2008 Open Public Comment Period for Preliminary Risk Assessments 3 rd Quarter 2009

Close Public Comment Period 4 th Quarter 2009
Phase 3: Registration Review Decision
Open Public Comment Period for Proposed Reg. Review Decision 1 st Quarter 2010

Close Public Comment Period 2 nd Quarter 2010 Final Decision and Begin Post-Decision Follow-up 2010 Total (years) 3

Guidance for Commenters The public is invited to comme nt on EPA’s preliminary regi stration 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 urea sulfate case.

Through the registration review process, th e 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 Le vels (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. Urea su lfate is exempt from the requirement of a tolerance, and there are no Codex MRLs; so trade irritants are not expected for urea
sulfate.

Stakeholders are also specifically asked to provide information and data in the following

areas: 1. Use or potential use distribution ( e.g. , acreage and geographical distribution of relevant uses). 2. Use history.
3. Median and 90 th percentile reported use rates (lbs. a.i. /acre) from usage data—national, state, and county. 4. Application timing (date of first a pplication and applic ation intervals) by use—national, state, and county.

55. Typical applicati on interval (days). 6. Usage/use information for non-agricultural uses ( e.g. , golf course, athletic fields, ornamentals). 7. Directly acquired county-level usag e data (not derived from state level data). a. maximum reported use rate (lbs. a.i./acre) from usage data—
country 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 used in the county/sub-county

area f. the years in which the pestic ide was applied in the county/subcounty area 8. Sub-county crop location data.
9. State or local restrictions. 10. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mort alities) not already reported to the Agency. 11. Monitoring data.
12. Urea Sulfate is not identified as a cause of impairment for any water bodies listed as impaired under sec tion 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 chemical. 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 Da ta in OPP’s Registration Review Risk Assessment and Management Process” information provided at http://www.epa.gov/oppsrrd1/registration_review/water_quality.htm ., in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Next Steps After the comment period closes, the Agency will prepare a Final Work Plan for this pesticide.

6II. FACT SHEET Background Information

• Urea Sulfate Registration Review Case Number: 7213

• Urea Sulfate PC Code: 128961, CAS#: 21351-39-3

• Technical Registrant: DuPont

• One technical product, and two end-use products (end-use products contain other active ingredients—et hephon and glyphosate).

• First product registered in 1987.

• Not subject to reregistration; thus, no Re registration Eligibility Decision (RED) is
available.

• Tolerances were reassessed as per FQPA in the Tolerance Reassessment Decision (TRED) completed in June 2005.

• Urea sulfate rapidly dissociates to urea and su lfuric acid and/or sulfate ions. Urea has been designated by FDA as Generally Recognized as Safe (GRAS), see 21 CFR 184.1923. In addition, sulfuric acid ha s been designated as GRAS for some uses when present in low concentrations.

• Special Review and Reregistration Divi sion (SRRD), Chemical Review Manager (CRM): Andrea Carone, carone.andrea@epa.gov

• Registration Division (RD), Product Manager (PM): Jim Tompkins, tompkins.jim@epa.gov

Use & Usage Information (For additional details, please refer to the BEAD Appendix A document in th e urea sulfate docket.)

• Urea sulfate can be used as an herbicid e, desiccant, and ha rvest-aid on various crops and non-crops including:

o Crops: Alfalfa, apples, barley, berrie s, citrus, corn, cotton, grass seed, oats, peanut, peppermint, potatoes, rice, tomatoes, tree fruit, tropical fruit, soybean, spearmint, vegetables, and wheat.

o Non-crops: Farmstead weed contro l, conservation reserve program, forestry site preparation, rights of way, ornamentals, nursery stock, Christmas tree plantings, pastures, fa llow and reduced tillage systems.

• Approximately 3,080,000 pounds of urea su lfate are used annually. The highest usage is on cotton, potatoes, tomatoes, and apples. Less than 1% of the crop of apples, potatoes, and tomatoes are treated.

• Currently there are no residential uses.

• Urea sulfate is formulated as a soluble concentrate/liquid.

• Urea sulfate may be applied by boom sprayer, high volume ground sprayer, low volume sprayer, hand held sprayer, wiper application, sh ielded applicator,
and aircraft.

Recent Actions

• A TRED was completed June 14, 2005 and r eassessed the tolerance exemption in or on all raw agricultural commodities when the product is used as an herbicide or
a desiccant (40 CFR 180.1084).

7• On July 18, 2006 three products were cancelled—SuperQuik, WilThin Blossom Thinner, and Enquik. This included one special local needs product.

• A new label for the technical was accep ted in February 2007. Entek was the technical registrant until the company was purchased by Griffin LLC. DuPont
owns Griffin LLC. The revi sed technical label has DuP ont as the sole technical registrant.

Ecological Risk Assessment Status : Please refer to Section III of this document, Ecological Risk Assessment Problem Form ulation, for a detailed discussion of the anticipated ecological risk assessment needs. Since urea sulfate rapidly dissociates to
urea and sulfuric acid and/or sulfate ions, EFED looked at the assessments of the constituent products—urea and sulfuric acid. Sulfate ions were not evaluated because they are not expected to pos e a significant ecological ris k. Below is a summary of the findings:

Urea Sulfate

• Urea sulfate is slightly to practically non-toxic to birds and fish.

• In a simulated avian field study birds dire ctly exposed to spray applications of urea sulfate showed eye and foot damage.

• There are no registrant-submitted studies for urea sulfate that address chronic mammalian toxicity, chronic fish toxicity, or chronic aquatic inve rtebrate toxicity. However, because of its fate properti es, chronic exposure is not expected. Nevertheless, an open literature search is planned.

• There are also no acute aquatic invertebrate or macrophyte toxicity data for urea
sulfate. A literature search is planned.

Urea

• Urea is practically non-toxic to freshwater fish, freshw ater invertebrates, and
birds.

• There are no registrant-submitted studies for urea that address environmental fate. However, available data illustrates that urea degrades rapidly in most soils, and therefore is not expected to leach into groundwater. Sulfuric Acid

• The Agency will use open literature data and information gleaned from studies
with urea sulfate to assess the ecotoxico logical effects of sulfuric acid. In addition, there are two sulfuric acid studi es pending review by the Agency: 1) a simulated ephemeral pond study, and 2) an irrigation water study, where the systems were titrated with urea dihydrogen sulfate.

• Based on the previously conducted hazard assessments, sulfuric acid resulting from the use of urea sulfate may pose a risk to terrestrial wildlife and also could lower the pH of very small and sha llow water bodies with a low buffering capacity, and therefore may harm aquatic organisms.

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. Below is a summary of the findings:

8Dietary (Food and Water):

• There are no dietary risks that exceed the Agency’s level of concern (LOC).

Residential

• There are no residential uses for urea sulfate.

Occupational

• Assessments completed on urea and sulfuric acid and/or sulfate ion indicate that occupational scenarios did not result in risks of concern.

Data Call-In (DCI) Status

• No outstanding DCIs.

Tolerances

• Urea sulfate is exempt from the requi rement of a tolerance in or on raw agricultural commodities when used as an herbicide or desiccant (40 CFR 180.1084).

• No MRLs for urea sulfate have been es tablished or proposed by Codex for any agricultural commodities.

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/pestlab1/ppls.home

.

Urea Sulfate Registrations

Registration Number Product Name Company Active Ingredient

352-673 Urea Sulfate-MP Dupont Urea Sulfate 352-674 (68891-7) ETK-2201 Dupont Urea Sulfate and Ethephon 352-675 (68891-8) ETK-2301 Dupont Urea Sulfate and Glyphosate

9III. ECOLOGICAL RISK ASSESS MENT PROBLEM FORMULATION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460

PC Code: 128961
DP Barcode: D337144 Date: July 20, 2007

MEMORANDUM

Subject: Registration Review Preliminary Problem Formulation for the Ecological
Risk Assessment of Urea Sulfate

To: Andrea Carone, Risk Manager
Mail Code: 7508P Special Review and Reregistration Division Office of Pesticide Programs

From: Fred Jenkins, MS, Biologist Ibrahim Abdel-Saheb, Ph.D., Environmental Scientist
Environmental Risk Branch 2
Environmental Fate and Effects Division Office of Pesticide Programs

Through: Dana Spatz, Acting Chief
Environmental Risk Branch 2
Environmental Fate and Effects Division Office of Pesticide Programs

Attached is the Environmental Fate and E ffects Division’s (EFED) preliminary problem formulation for the ecological risk assessm ent to be conducted as a part of the Registration Review of the agricultural uses of urea sulfate as a desi ccant and an active ingredient in herbicides.

10R EGISTRATION R EVIEW



## E COLOGICAL 

## R ISK 

## A SSESSMENT 

## P RELIMINARY PROBLEM FORMULATION FOR 

## :



## U REA 

## S ULFATE

P REPARED B Y :

Fred Jenkins, MS, Biologist Ibrahim Abdel-Saheb, Ph.D., Environmental Scientist
Environmental Risk Branch 2
Environmental Fate and Effects Division Office of Pesticide Programs

A PPROVED B Y :

Dana Spatz, Acting Chief
Environmental Risk Branch 2
Environmental Fate and Effects Division Office of Pesticide Programs

11S TRESSOR S OURCE AND D ISTRIBUTION

Urea sulfate (CAS Number 21351-39-3 ) is an active ingredient in herbicides and is used as a desiccant on agricultural crops. Acco rding to the Office of Pesticide Programs Information Network (OPPIN) two products are currently registered with urea sulfate as an active ingredient. These products ar e ETK-2301 and ETK-2201. Table 1 displays further details regarding both of these products. ETK-2201 is used as a cotton harvest
aid/defoliant and ETK-2301 is used as an herb icide on a large variety of crops listed in Table 2. Table 3 displays the screening level estimates of the 1999 thru 2005 agricultural uses of Urea Sulfate conducted by the Offi ce of Pesticde Programs Biological and Economic Analysis Division (BEAD). This analysis was based on data from the US Department of Agriculture’s National Agricu ltural Statistics Service (NASS). This analysis indicates that although urea sulfat e is registered for use on a multitude of different crops, the actual usage of th is chemical during recent years has been predominantly limited to apples, cotton, potatoes, and tomatoes.

Based on the conclusions of the Ecological Effects Branch Hazard Assessment dated 1984, EFED currently surmises that the sulfuric acid acts as the primary herbicidal active ingredient for the urea sulfate products. The sulfuric acid appa rently acts via the catalyzation of hydrolysis of cellulose which results in the dissolu tion of the vegetative tissue. Urea sulfate readily dissociates to urea and sulfuric acid. Therefore, this preliminary problem formulation will evaluate the potential ecologi cal effects of urea,
and sulfuric acid individuall y. Both urea and sulfuric aci d are registered pesticides.

Table 1. Registered Products of Urea Sulfate (according to OPPIN 1 )

Reg.
Number Product
Name Percent
Urea
Sulfate Other Active Ingredients Formulation Type Specific Use Date first registered

68891-7 ETK-2201 58.6 18.3% ethephon Soluble concentrate Cotton harvest
aid/defoliant only Feb. 1996

68891-8 ETK-2301 71.1 9.6% glyphosate Soluble concentrate Herbicide on a variety of

crops Dec. 1996

1 Note: OPPIN (Office of Pesticid e Programs Information Network) :

12Table 2. ETK-2301 Use Crops Type Crops Crops Row Crops Corn, Cotton, Peanuts, and Soybeans

Forage Legumes Alfalfa, Peanuts, and Soybeans

Cereal Grains Barley, Oats, Millets, Rice, Rye, Triticale, and Wheat (All)

Tree Fruits Apple, Apricot, Ch erry, Nectarine, Olive, Peach, Pear, Plum, Plumcot, and Prune

Tree Nuts Almond, Beechnut, Brazil Nut, Butternut, Cashew, Chestnut, Filbert, Hickor y Nuts, Macadamia Nut, Pecan, Pistachio, and Walnut Vine Crops Grapes Tropical Crops Avocado, Banana, Coffee, Dates, Figs, Guava, Papaya, Passion Fruit, Persimmon, Pineapple, Plantain, Vegetables Asparagus, Beans (A ll), Broccoli (All), Brussels Sprouts, Cabbage (All), Chinese Cabbage, Cantalope, Cauliflower, Casaba Melon, Celery, Chard Swiss, Collard, Cren shaw Melon, Cucumber, Eggplant, Endive, Garlic, Gourds, Honeydew Melon, Honey Melon, Kale, Kohlrabi, Leek, Lettuce, Mango Melon, Melons (All) Muskmelon, Mustard Greens, Onion (All ), Parsley, Peas (All), Pepper (All), Persian Melon, Potato, Pumpkin, Rape Greens, Rhubarb, Spinach (All), Squash (Winter, Summer), Sugarbeet, Tomatillo, Tomato, and
Watermelon.

Table 3. Screening Level Estimate s of Agricultural Uses of Urea Sulfate (BEAD, October 2006 )

Percent Crop Treated * Crop Lbs. A.I.

Avg. Max.

Apples 10,000 <1 <2.5

Cotton 2,900,000 5 10

Potatoes 90,000 < 1 < 2.5

Tomatoes 80,000 <1 <2.5

Notes:
* All numbers rounded. '<2.5' and < 1i ndicates less than 2.5 percent of crop a nd 1 percent of crop respectively is

treated.

13I NTEGRATION OF A VAILABLE I NFORMATION

The following Agency risk assessment documents available in the Office of Pesticides Program Regulatory Docket serve as the basis for this preliminary problem formulation:

U.S. EPA, June 2005 Tolerance Reassessment Eligibility Decision (TRED)
Document for Urea Sulfate

U.S. EPA Pesticide Registration Deci sion (RED) document for Mineral Acids (The mineral acids include four differe nt active ingredients including sulfuric acid, the herbicidal active ingredient of urea sulfat e. Each of the active ingredients was evaluated independen tly within the RED document. The
evaluation of sulfuric acid in the Mineral Acids RED will be used as a resource for this preliminary problem formulation).

U.S. EPA Ecological Effects Branch , September 1989. Risk Assessment for Terrestrial Organisms Exposed to Enquik

Ecological Effects Branch, February 21, 1989. Urea Sulfate - Review of Proposed Registration of New Crops and Expansion of Geographic Areas from
Previous Label

E COLOGICAL E FFECTS

T OXICITY S TUDIES

Registrant Submitted Studies for Urea Sulfate

The registrant submitted studies include one fi sh acute toxicity study, an acute oral rat toxicity test, two avian acut e dietary studies, one aquatic pl ant toxicity st udy, and three terrestrial plant toxicity studies includi ng a vegetative vigor study, a seedling emergence study, and a seed germination study. Also, one simulated avian field study has been submitted by the registrant.

The acute toxicity studies test ing fish, birds, and mammals de monstrated that urea sulfate is slightly to practic ally nontoxic to these organisms. The results of the plant toxicity studies were as follows. The vegetative vigor results demonstrated that the tomato was the most sensitive species with an EC 50 of 12 lb a.i. /acre for fresh and dry weights. The most sensitive NOECs for these parameters were 1.2 and 4.7 lbs. a.i. /acre for tomato and radish respectively. The seed germination st udy demonstrated that seed germination was not inhibited by more than 9.7% in any of 10 plant species tested. The NOEAC of this study was > 37.5 lb a.i./acre. The results of the seedling emergence study showed that seedling emergence was not inhibited anym ore than 14% among any of the species tested. The algal toxi city study demonstrated a Selenastrum capricornutum EC 50 of 11.5 ppm. The results of the avian simulated fiel d study demonstrated that birds exposed to

14spray applications of urea sulfate displayed significant eye and foot damage that may be pronounced for birds exposed to direct applicat ions of undiluted urea sulfate. The results
also concluded that dilu ted urea sulfate causes some, but much less, damage.

Data demonstrating the toxicity of urea sulfate to aquatic invertebrates have not been submitted. However, the Agency presumes that urea sulfate will not pose a significant toxic concern to aquatic inve rtebrates based on the following rationale. The available registrant submitted toxicity data demonstrat e that urea sulfate has low acute toxicity (only slightly to practically nontoxic) to birds, mammals, and fish. Since urea sulfate has demonstrated low toxicity to all animals test ed, it is expected to also demonstrate low toxicity to aquatic invertebrate s. In addition, urea sulfate degrades rapidly into urea and sulfuric acid, neither of which is expected to pose a significant risk to aquatic invertebrates because; 1) urea has been s hown to be practically nontoxic to aquatic invertebrates (see below, Registrant Submitted Studies for Urea ) and 2) sulfuric acid is expected to readily dissoc iate into sulfate ions wh ich are innately nontoxic.

Registrant Submitted Studies for Urea

There are four registrant submitted ecotoxicity studies for urea. These include two
freshwater fish acute toxic ity studies, one freshwater i nvertebrate study, and one avian acute dietary toxicity study. These studies i ndicate that urea is practically nontoxic to freshwater fish, freshwater invertebrates, a nd birds (birds practica lly nontoxic on an acute dietary basis).

Registrant Submitted Studies for Sulfuric Acid

The registrant has not submitted any data to evaluate the ecotoxicological effects of sulfuric acid independently as an active ingr edient. However, because sulfuric acid is expected to readily dissociate into innately non-toxic sulfate ions, EFED does not expect sulfuric acid to pose a significant toxicological hazard to nontarget organisms. Additionally, available aquatic toxicity data based on a preliminary search of the EPA
ECOTOX database indicates that sulfuric acid is only slightly acutely toxic to fish and aquatic invertebrates (Table 4). Furthermor e, the available registrant submitted studies testing urea sulfate contai ned up to 49% sulfuric acid, and these studies also demonstrated low toxicity to terrestrial and aquatic animals. Therefore, because of the low toxicity of sulfuric acid as demonstrat ed by the studies evaluated thus far and the available registrant submitted studies testi ng urea sulfate, EFED does not believe it necessary to require additional toxi city data for sulfuric acid.

15Table 4. Results Preliminary ECOTOX Database Search Species (Common name) Test
Duration

(Days) LC 50 (ppm) Test Type ECOTOX
Reference

Carcinus

maenas (Green or Europeon shore crab) 2 70-80 (slightly toxic) Saltwater lab 906

Crangon

crangon (Common shrimp, sand shrimp 2 70-80 (slightly toxic) Saltwater lab 906

Pandalus (Aesop shrimp montagui) 2 42.5 (slightly toxic) Saltwater lab 906

Daphnia magna (Water flea) 7 20 (slightly toxic) Freshwater 916

Cerastoderma
edule (Cockle) 2 200-500 (slightly toxic) Saltwater 906

Fish Species (Common name) Test
Duration

(Days) LC 50 (ppm) Test Type ECOTOX
Reference

Agonus cataphractus
Hooknose 2 80-90 (slightly toxic) Saltwater Lab 906

Gambusia
affinis Western mosquitofish 4 42 (slightly toxic) Freshwater Lab 508

Platichthys flesus (Starry,

european flounder) 2 100-330 (slightly toxic) Saltwater Lab 906

I NCIDENT R EPORTS

According to Office of Pesticides Program Ecological Incident Information System (EIIS), there is one incident in Kern County California report edly classified as a possible incident resulting from use of a Lorsban pesticide tank mix which included urea and sulfate as ingredients. The total ingredients in the Lorsban tank mix included zinc sulfate, manganese sulfate, urea, potassium n itrate, manganese nitrate. The Lorsban tank mix was applied to a tangelo crop on Apr il 4, 2001. The tangelos began exhibiting ridging symptoms. The ridging lowered the grade of the fruit which consequently lowered the potential economic gains of the crop. Insufficient evidence was available to
determine if urea sulfate or one of the othe r ingredients in the tank mixture caused the ridging.

16E XPOSURE C HARACTERISTICS

Urea

EFED has no registrant submitted fate data for urea. Information on the environmental fate, as summarized in the Hazardous Substances Data Bank (http://toxnet.nlm.nih.gov/) and cited in previous EFED re views may be found below.

Biodegradation is expected to be the major fate process in the aquatic ecosystem. Various screening studies have demonstrated that ur ea can biodegrade readily with the release of

CO 2 and ammonia. The rate of biodegradat ion generally decreases with decreasing temperatures; under cold winter-like conditions , biodegradation may be relatively slow (0-6% per day). The presence of natura lly-occurring phytoplankton increases the degradation rate because phytoplankton uses ur ea as a nitrogen source and because urea is decomposed by phytoplankton via photosynthe sis. In phytoplankton-rich waters, degradation occurs much faster in sunlight than in the dark.

If released to air, a vapor pressure of 1.20x10 -5 mm Hg at 25 0 C, indicates urea will exist in both the vapor and partic ulate phases in the ambien t atmosphere. Vapor-phase urea will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 9.6 hrs. Particulate-phase

urea will be removed from the atmosphere by wet and dry deposition.

In various soils, the hydrolysi s may near completion within 24 hours. Abiotic hydrolysis of urea occurs very slowly in relation to biotic hydrolysis. Abiotic hydrolysis yields ammonium carbamate which decomposes to form CO 2 and ammonia; the enzyme urease catalyzes urea hydrolysis.

In one photodegradation study using a silica gel adsorbent, only 0.2% of applied urea photomineralized after a 17-hr irra diation with a UV lamp (>290 nm).

The adsorption of urea was measured in six different British soils with organic carbon contents ranging from 1.76 to 36.5%; no adsorpti on was measurable in five of the soils; in the sixth soil (36.5% organic carbon), a K OC of 8 can be determined from the measured
Freundlich isotherm

.

BCF values of 1 and <10 suggest bioconcen tration in aquatic organisms is low.

There appears to be no drinking water concerns for urea. Because of the low toxicity of urea and the subsequent lack of toxicity endpoints for use in risk assessment, drinking water levels of comparison (DWLOC s) were not calculated for urea (http://www.epa.gov/pestic ides/reregistration/REDs/urea_tred.htm).

In conclusion, available data from literature reviews show that urea degrades rapidly in most soils. Soil adsorption studies have dem onstrated that urea adsorbs very weakly to

17soil; however, because urea degrades rapidly, leaching to groundwater in appreciable amounts is not expected. Ultimate urea degradation produces ammonia and CO 2 .

Sulfuric Acid

The mineral acids generally dissociate and release hydrogen ions in the environment; thus increasing the pH of soil and water. Sulfuric acid will ultimately react with calcium and magnesium in water to form sulfate salts.

Two studies had been previously submitte d, one being a simulated ephemeral pond study, consisting of 5 gallon buckets, 6 inches of soil (8 various type s) and 6 inches of distilled water. Enquik had been sprayed at a rate of 50 gal/A and 100 gal/A.

The data indicated that there was little diffe rence between the ponds treated with the 50 gal/A, and the ponds (buckets) tr eated with 100 gal/A. All treated buckets plummeted to a pH of approximately 2.5 within the first day of treatment. One soil i ndicated that the pH did not go higher than 5 until 21 days postappl ication. In a second study, 12 irrigation waters, collected from California and Arizona irrigation systems, were titrated with Urea dihydrogen sulfate (N-TAC DESSICANT) to a pH of 4.5. The data indicate that an average of 33 gallons of N-TAC/A in 6 inch es of water will lower the pH to 4.5. The actual values ranged from 11 gallons to 42 gallons of N-TAC/A in 6 inches water were required to lower the pH to 4.5.

It is important to note that these studies were conducted in only 6 inches of water. The studies are pending review by EFED.

Monitoring Data:

EFED has no monitoring data on the concentrati ons of urea sulfate, ur ea or sulfuric acid in surface or groundwater.

C HARACTERISTICS OF E COSYSTEMS P OTENTIALLY AT R ISK

As previously mentioned, urea sulfate readily dissociates to urea and sulfuric acid and/or sulfate ions in the environment. Therefore, this preliminary problem formulation will
evaluate urea and sulfuric acid. The sulfate io ns will not be evaluated because they aren’t expected to pose significant ecological risk, due to their innately non-toxic nature and their naturally abundant occurr ences in the environment.

For urea sulfate and pesticides in general, th e ecosystems at greatest risk are those in close proximity to the use areas. These would include agricultural fields (surrounding non-agricultural terr estrial habitats) and water bodies directly adjacent to treated fields that may receive chemical residues via drift, volatilization, and/or runoff. Within water bodies, the water co lumn, sediments, and pore water are all compartments of concern.

18Organisms of concern include birds, mammals, reptiles, fish, and terrestrial and aquatic invertebrates, plants, and amphibians. The assessment endpoints are intended to reflect population sustainability and community struct ure 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.

A SSESSMENT E NDPOINTS

Assessment endpoints are defined as “explicit expressions of the ac tual environmental value that is to be protected.” Defining an assessment endpoint involves two steps: 1) identifying the valued attributes of the envir onment that are considered to be at risk; and 2) operationally defining the assessment endpoint in terms of an ecolo gical entity (i.e., a community of fish and aquatic invertebrate s) and its attributes (i.e., survival and reproduction). Therefore, selection of th e assessment endpoints is based on valued entities (i.e., ecological recep tors), the ecosystems potential ly at risk, the migration pathways of pesticides, and the routes by which ecological receptors are exposed to pesticide-related contamination. The selecti on of clearly defined assessment endpoints is important because they provide direction a nd boundaries in the ri sk assessment for addressing risk management issues of c oncern. Changes to assessment endpoints are typically estimated from the available toxicity studies, which are used as the measures of effects to characterize potentia l ecological risks associated w ith exposure to a pesticide,
such as urea sulfate.

The most sensitive toxicity endpoints are used from surrogate test species to estimate
treatment-related direct eff ects on acute mortality and chr onic reproductive, growth and survival assessment endpoints. Toxicity te sts are intended to determine effects of pesticide exposure on birds, mammals, fish, te rrestrial and aquatic invertebrates, and plants. These tests include short-term acu te, sub-acute, and repr oduction studies and are typically arranged in a hierarchical or tiered system that progresse s from basic laboratory tests to applied field studies. The toxicity st udies are used to evaluate the potential of a pesticide to cause adverse effects, to determ ine whether further tes ting is required, and to determine the need for precautionary label st atements to minimize the potential adverse effects to non-target animals and plants. Th e following is a summarization of the most sensitive endpoints from the av ailable ecotoxicity data.

Urea Sulfate Most Sensitive Endpoints

Birds

The acute toxicity studies demonstrated that urea sulfate is practica lly non-toxic to birds. (studies demonstrated no mort alities to test birds). Thus, there are no acute toxicity endpoints for birds.

19Mammals

The most sensitive mammalian acute oral toxicity endpoint was a rat acute oral LD 50 of > 5000 mg/kg.

Fish

The most sensitive fish acute toxicity endpoint for urea sulfate is a Three spine
Stickleback LC 50 of 80 ppm (ACC072861).

Aquatic Invertebrates

Urea sulfate toxicity endpoint s have not been determined for aquatic invertebrates.

Aquatic plants

The most sensitive algal toxicity endpoint for urea sulfate is a Selenastrum capricornutum EC 50 of 11.5 ppm (MRID 433681-01).

Terrestrial Plant Toxicity

The vegetative vigor results demonstrated that the tomato was the most sensitive species.
The tomato demonstrated an EC 50 of 12 lb a.i./acre for fresh and dry weights. The most sensitive NOECs for these parameters were 1.2 and 4.7 lbs. a.i. /acre for tomato and radish respectively (MRID 433681-03). The se ed germination and seedling emergence
studies demonstrated that urea sulfate ha d insignificant toxic effects on the endpoint parameter measured in these studies (MRID 433755-02).

Urea Most Sensitive Endpoints

There are no urea endpoints for freshwater fish, freshwater invertebra tes, or birds because urea is practically nontoxic to all these organisms (LC 50 and EC 50 values were higher than the highest values tested in any of the studies for these organisms).

Most Sensitive Endpoints for Sulfuric Acid

The Agency will use open literature data and information gleaned from studies with urea sulfate to assess the ecotoxicologi cal effects of sulfuric acid.

C ONCEPTUAL M ODEL

In order for a chemical to pose an ecologica l risk, it must reach ecological receptors in biologically significant concen trations. 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,

20an environmental transport medium, a point of exposure for ecologi cal receptors, and a feasible route of exposure.

The conceptual model ( Figure 1 ) depicts the potential path ways for ecological risk associated with urea sulfate, urea and sulfur ic acid. The conceptual model provides an overview of the expected exposure routes fo r organisms within th e urea sulfate action area. For terrestrial organisms, the major route of exposure considered is the dietary route; consumption of food items such as plan t leaves or insects th at have urea sulfate residues as a result of spraying, drift, and vol atilization. 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 con centrations for all organisms are obtained through the use of several Agency exposure models.

R ISK H YPOTHESIS

Based on an examination of the physical/chemica l properties of urea su lfate, the fate and disposition in the environm ent, and mode of applica tion, a conceptual model was developed that represents the possible rela tionships between the stressor, ecological receptors, and the assessment endpoints. EFED predicts that once ur ea sulfate enters the environment it will readily dissociate into urea and sulfuric acid. EFED also predicts that the sulfuric acid may pose at least two primar y environmental threats. Firstly, sulfuric acid may contaminate surface waters in close proximity to the urea sulfate use sites by way of spray drift. Once the water bodies are contaminated with sulfuric acid, they could potentially, depending upon volume and concentrat ion, be subject to changes in pH. The change in pH could potentially pose an advers e threat to the inhabitants of these water bodies. Secondly, EFED predicts terrestrial organisms that co me in direct contact with the sulfuric acid may be at risk of experien cing the corrosive effects this chemical can
have on tissue.

21F IGURE 1. E COLOGICAL CONCEPTUAL DIAGRAM FOR U REA SULFATE

Application of urea sulfate formulated products, ETK-2201 and ETK-2301 to Row Crops, Forage Legume Crops, Cereal Grains, Tree Fruits and Nuts, Vine Crops, Tropical Crops, and Vegetables Stressor

Source: Transport Pathway Direct Ground Deposition Spray Drift Volatilization Wind Suspension Runoff/

Erosion Leaching

Source: Exposure

Media (Media

Contamination by Urea

and Sulfuric acid Terrestrial Food Residues (foliage, fruit, Insects;) Upland Soil And Foliage Riparian/Wetland Foliage/Soil Surface Water

Sediment Groundwater

Exposure Point Direct Contact And Ingestion Direct Contact/ Root Uptake Uptake/Adsorption Gill/Integument Uptake

Receptors Terrestrial Vertebrates and

Invertebrates Terrestrial Upland

Plants Riparian/Wetland

Plants Aquatic Plants Aquatic Invert and Vertebrates

Direct Effects Terrestrial Animal •Lethality •Reproductive/ developmental

Effects

•Other adverse

sublethal effects ie. Corrosivity effects Non-Target Plants •Plant growth abnormalities •Lethality •Developmental/reproductive

effects Plant Population Reduced Population growth Aquatic Animals and Plants •Effects to survival, growth, and Reproduction •Reproduction in cell density/biomass in aquatic plants

• Other adverse sublethal effects

Indirect

Effects Altered Terrestrial Community Assemblages or habitat: Reduced food supply and edge habitat availability Altered Aquatic Community Assemblages or habit: Effects to habitats ie potential changes to pH of aquatic

habitat

22A NALYSIS P LAN O PTIONS

In Registration Review, pesticide ecological risk assessments will follow the Agency’s Guidelines for Ecological Risk Assessment and will be in compliance with the paper titled “Overview of the Ecological Risk Asse ssment Process in the Office of Pesticide Programs, U.S. Environmental Protection Ag ency” (“Overview Document”) (January 2004), and will address obligations under Sect ion 7 of the Endangered Species Act.

A screening level ecological risk assessment has never been conducte d for urea sulfate. The only type of ecological assessments that the Agency has conducted for the agricultural use of urea sulfate are “hazard a ssessments.” These types of assessments were conducted prior to the Agency’s po licy implementing that “ecological risk assessments” be conducted to assess the potentia l ecological harm of pesticides. Hazard assessments evaluated the ecological effects of a pesticide by focusing only on the toxic effects of a pesticide to non-targ et organisms. The focus of an ecological risk assessment
is on both the toxic effects of a pesticide to non-target organi sms and the potential routes of the pesticide’s exposure to non-target organisms. In addition to addressing a pesticide’s toxic effects and pot ential routes of exposure, an ecological risk assessment
addresses the uncertainti es associated with a pesticide’ s risk to non-target organisms.

EFED will utilize the Agency’s most recently conducted hazard assessments and all the data that support th ese assessments as a resource fo r conducting the ecological risk assessment for the registration review process. These hazard assessments include the following:

Ecological Effects Branch, February 21, 1989. Urea Sulfate - Review of Proposed Registration of New Crops a nd Expansion of Geographic Areas from Previous Label

U.S. EPA Ecological Effects Branch, Septem ber 1989. Risk Assessment for Terrestrial Organisms Exposed to Enquik

The conclusions of these documents were as follows:

• Urea Sulfate usage may pose a risk to terrestrial wildlife. This risk is primarily
attributed to the corrosive nature of urea sulfate which can potentially cause damage to the terrestrial animal’s exposed body parts.

• Urea Sulfate usage may introduce sulfuric acid to water bodies in close proximity
to the use sites. The sulfuric acid coul d lower the pH of very small and shallow water bodies with low buffering capacit y, and therefore may harm aquatic organisms.

Additionally, EFED notes there was a US Fish and Wildlife Service (USFWS) 1989 Biological Opinion regarding the nation wide use of urea sulfate on a variety of vegetables, fruit, and nut tree crops. While some of the information available in this

23document may be useful, other portions coul d be outdated and no longer applicable due to changes in labels, use patterns, etc.

A NTICIPATED D ATA N EEDS

Although the guideline ecotoxicity data set is not complete for urea sulfate and sulfuric acid, the Agency does not foresee requiri ng any additional ecol ogical effects or environmental fate studies prior to conducti ng the planned assessments (see Table 5). The Agency will however conduct a search of th e 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 databa ses – 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.

Table 5. Evaluation of the need for additional effects data on urea sulfate, urea, and sulfuric acid Guideline study title Chemical Projected status of data gap Basis for decision

Gdln. 72-2(a): Freshwater Aquatic Invertebrate Toxicity Study (TGAI) Urea Sulfate Study not requested

at this time The Agency presumes that urea sulfate will not pose a significant toxi c concern to aquatic
invertebrates based on th e following rationale. The available registrant submitted toxicity data
demonstrate that urea sulfate has low acute toxicity (only slightly to practically nontoxic) to birds, mammals, and fish. Since urea sulfate has demonstrated low toxicity to all animals tested, it is expected to also demonstrate low toxicity to aquatic invert ebrates. In addition, urea sulfate degrades rapidly into urea and sulfuric acid, neither of which is expected to pose a significant risk to aquatic invertebrates because; 1) urea has been shown to be practically nontoxic to aquatic invertebrates, and 2) sulfuric acid is expected to readily dissociate into sulfate ions which are innately nontoxic and naturally and abundantly occur in
the environment.

71-1(a): acute avian oral, (TGAI) Sulfuric

acid Study not requested

at this time Because sulfuric acid is expected to readily dissociate into innately non-toxic sulfate ions, EFED does not expect su lfuric acid to pose a significant toxi cological hazard to nontarget organisms. Additionally, available aquatic toxicity data based on a preliminary search of
the EPA ECOTOX database indicates that sulfuric acid is only slightly acutely toxic to fish and aquatic invertebrates (Table 4). Furthermore, the availabl e registrant submitted studies testing urea sulfate contained up to 49% sulfuric acid, and these studies showed no concerns for acute avian toxicity.

24O THER I NFORMATION N EEDS

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

e. frequency of application, applicati on intervals, and maximum number of applications per season
f. geographic limitations on use

2. use or potential use distri bution (e.g., acreage and geogr aphical distribution of relevant crops)

3. 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 first applica tion and application intervals) by crop – national, state, and county

6. sub-county crop location data

7. usage/use information for non-agricultural uses (e.g., forestry, residential, rightsof-way)

8. 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

9. typical interval (days)

10. state or local use restrictions

11. ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

12. monitoring data

The analysis plan will be revisited and potenti ally revised depending upon the data available in the open literature and the info rmation submitted by the public in response to the opening of the Registration Review docket.

25IV. HUMAN HEALTH EFFECTS SCOPING DOCUMENT

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES AND
TOXIC SUBSTANCES

MEMORANDUM

May 10, 2007

SUBJECT: Urea-sulfuric acid adduct: Registra tion Review Scoping Document for Human Health Assessments; PC Code 128961; DP Barcode D337871.

FROM: Ray Kent, Chief Sue Hummel, Chemist Reregistration Branch 4 Health Effects Division (7509P)

TO: Andrea Carone Special Review Branch 1 Special Review and Rere gistration Division (7508P)

Attached is the human health scoping/problem formulation document to support the registration
review of the herbicide and de siccant, urea-sulfate adduct.

Introduction

The HED Urea Sulfate Registration Review Team has evaluated the status of the human health assessments for the herbicide, desiccant, and harvest aid, urea sulfate to determine the scope of work necessary to support registration review. The team looked at the hazard and exposure databases for urea sulf ate and determined whether changes in science policy or deficien cies in the databases materially affected the overall risk picture

The Agency has determined that urea sulfate rapidly degrades to urea and sulfuric acid

and/or sulfate ions in the human body and the environment. Urea is a natural product, which humans synthesize in large quantitie s during normal metabolis m. Urea has been

26designated by FDA as Generally Recogni zed as Safe (GRAS) (see 21 CFR 184.1923). Sulfuric acid produces sulfate salts in the environment, many of which are designated as GRAS, and sulfuric acid is designated as GR AS for some uses in low concentrations.

Urea-sulfuric acid adduct is currently registered (on the technical label) for use on numerous raw agricultural commodities, as an herbicide, desiccant, or harvest aid, as
shown in Table 1. Urea-sulfuric acid a dduct currently has an exemption from the requirement of a tolerance when used as an he rbicide or desiccant in all raw agricultural commodities (40 CFR 180.1084). There are currently no residential uses for urea sulfate.

Table 1

. Urea Sulfate Use Pattern

Row Crops: Alfalfa, Clover, Corn (All), Cotton, Peanuts, Soybeans Cereal Grains: Barley, Millet, Oats, Rice, Rye, Triticale, Wheat (All) Tree Fruits: Apple, Apricot, Cherry, Nect arine, Olive, Peach, Pear, Plum, Plumcot,

Prune Tree Nuts: Almond, Beechnut, Brazil Nut, Butternut, Cashew, Chesnut, Filbert (Hazelnut), Hickory Nut, Macadamia Nut, Pecan, Pistachio, Walnut Citrus: Calamondin, Chironja, Citron, Grapefruit, Kumquat, Lemon, Lime, Mandarin Orange, Orange (All), Pu mmelo, Tangelo, Tangerine, Tangors Vegetables: Asparagus, Beans (All), Broccoli (All), Brussels Sprouts, Cabbage (All), Cabbage (Chinese), Cantaloupe, Cau liflower, Casaba Melon, Celery, Chard (Swiss), Collards, Crenshaw Melon, Cucumber, Eggplant, Endive, Garlic, Gourds, Honeydew Melon, Honeyball Melon, Kale, Kohlrabi, Leek, Lettuce, Mango Melon, Melons (All), Muskmelon, Mustard Greens, Onion (All), Parsley, Peas (All), Pepp er (All), Persian Melon, Potato, Pumpkin, Rape Greens, Rhubarb, Spin ach (All), Squash (Summer and Winter), Sugarbeet, Tomatillo, Tomato, Watermelon Vines: Grapes Tropical Fruits: Avocado, Banana, Coffee, Da tes, Figs, Guava, Papaya, Passion Fruit, Persimmon, Pineapple, Plantain Berries: Blackberry, Blueberry, Boysenberry , Cranberry, Elderberry, Huckleberry, Raspberry Other Crops: Grass Seed, Peppermint Spearmint Noncrop Uses: Farmstead Weed Control; Cons ervation Reserve Program (CRP); Forestry Site Preparation, Rights of Way; Ornamentals, Nursery Stock, Christmas Tree Plantings, Pastures, Fallow and Reduced Tillage Systems

The last comprehensive review of urea sulfate was the Tolerance Reassessment Eligibility Decision (TRED), completed June 2005. In the TRED, the existing exemption from the requirement for a tolerance for urea sulfate was reassessed per FQPA. Urea
sulfate is used both as an herbicide and desi ccant (each current label actually lists this active ingredient as 1-aminomethanamide dihydrogen tetraoxosulfate). This active ingredient was first registered in 1987.

27The Agency has determined that urea sulfate readily degrades to urea and sulfuric acid
and/or sulfate ions in the envi ronment and in the human body.

Section 1. Chemical Identity

Table 1.1 Chemical Identity

Common Name Urea-sulfuric acid adduct Monocarbamide dihydrogen sulfate

IUPAC name 1 -aminomethanamide dihydrogen tetraoxosulfate

CAS name Urea, sulfate (1:1)

PC Code 128961 CAS registry number 21351-39-3 Registration Review

Case No. 7213

Chemical Structure

Section 2. Toxicology

No toxicity studies have been received sin ce the last human health risk assessment was completed for the TRED in 2005. A compre hensive search of the open literature was not done primarily because a screening G oogle search (Google Scholar) and a Science
Direct search indicated little new inform ation relevant to the human health risk assessment has been published on this herbicid e that had not already been considered in previous assessments.

The data requirements for the higher tier toxi city studies have all been waived by the Agency, and there are no repeated dose toxic ity studies available fo r urea sulfate.

The acute toxicity prof ile of urea sulfate is presented in Table 2.

28Table 2. Acute Toxicity Profile for Urea Sulfate

Study Type Species Results Toxicity Category Reference

Acute Oral Rat 1,200 mg/kg (male) 350 mg/kg (female) II

Acute Dermal Rabbit >2 g/kg Study terminated at 48 hrs because of extreme
caustic action and dermal necrosis. Not
determined

Acute
Inhalation Rat >10.8 mg/L III

Primary Eye

Irritation Rabbit Severe corneal involvement, grade 4 chemosis of conjunctivae at 24 hrs. I

Primary Skin

Irritation Rabbit Caustic on intact and abraded skin at 24 hours. Study was terminated at 24 hours after similar results
were obtained with 1:4 v/v dilution with water I EPA Pesticide
Fact Sheet

(1987)

Data from repeated dosing toxicity studies w ith animals does not exist for urea sulfate. However, urea sulfate readily degrades to urea and sulfuric acid and/ or the sulfate ion in the body. Based on the toxicity data reviewed (urea and sulfuric acid and its salts documents) for the 2005 TRED, there are no adve rse effects that would be expected in
infants and children for urea sulfate. For ur ea, animal studies provide no evidence of developmental or teratogenic effects. In an aque ous environment, sulfuric acid rapidly
ionizes to sulfate ions which are of no toxicological concern to infants and children. For these reasons, a safety factor analysis has not been used to assess the risks resulting from the use of urea sulfate; therefore, an additional tenfold safety factor for the protection of
infants and children is unnecessa ry, and can be reduced to 1x.

Section 3. Current Dietary Assessments

Based on the dissociation of urea sulfate in the human body to urea and sulfuric acid and/or sulfate ion, and the results of the RE Ds and TREDs for these constituent products, the Agency has determined that only a qua litative dietary assessment is needed. The Agency has determined that there are no dietary risk concerns, whether from the ingestion of food or water or both, for urea su lfate (or at least for the consumption of products containing urea sulfate as the sole active ingredient).

29Section 4. Aggregate and Cumulative Exposure

There are no residential uses for urea sulf ate. No aggregate exposure assessment is needed, given the lack of human health concer ns associated with exposure to urea sulfate, as well as its constituent products (urea a nd sulfuric acid and/or sulfate ions).

EPA does not have, at this time, available da ta to determine whether urea sulfate has a common mechanism of toxicity with other substances. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mech anism of toxicity,
EPA has not made a common mechanism of toxi city finding as to urea sulfate and any other substances, and urea sulf ate does not appear to produc e a toxic metabolite produced by other substances.

Section 5. Occupational Exposure

As mentioned above, the Agency has determin ed that urea sulfate readily breaks down
into urea and sulfuric acid and/or sulfate i on in the environment and in the human body. Assessments performed on both these compound s indicate no reasonable certainty of
harm to human health from either the EPA -registered uses or the FDA-GRAS uses. Therefore, it has been determined that the use of products containi ng urea sulfate would not present a human health hazard to occupa tional workers or the general public.

Section 6. Anticipated Data Needs

The Agency does not expect to require any ad ditional data for urea sulfate. There are several unreviewed product chemistry studies which will be reviewed later in the process.

Section 7. Tolerances/Exemptions fr om the Requirement of a Tolerance

The following table lists the current U.S. exemptions from the requirement of a tolerance for urea sulfate (40 CFR 180.1084).

Table 7.1. Exemption from the Requirement for a Tolerance Being Reassessed for Urea Sulfate

Tolerance Exemption Expression CAS No. 40 CFR PC Code Use Pattern

Active Ingredient

“monocarbamide dihydrogen sulfate” 21351-39-3 180.1084 128961 as an herbicide or desiccant

30Section 8. Overall Conclusions

The qualitative risk assessments for dietary and occupational exposur e to urea sulfate are up to current standards.

Section 9. Reference Memoranda

Table 9.1. HED Memoranda Relevant to Registration Review

Author Barcode Date Title

SRRD
-- 6/14/2005 Tolerance Reassessmen t Eligibility Decision: Urea Sulfate

31V. GLOSSARY OF TERMS AND ABBREVIATIONS

ai Active Ingredient AR Anticipated Residue CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formula CSFII USDA Continuing Survey s for Food Intake by Individuals
DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison
EC Emusifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration
EEC Estimated Environmental Concentration EPA Environmental Protection Agency
EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model
IR Index Reservoir

LC 50 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 expresse d 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 statistica lly derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (o ral, dermal, inhalation). It is expressed as a weight of substan ce per unit weight of animal, e.g., mg/kg.

LOC Level of Concern

LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Microgram Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter

MOE Margin of Exposure

MRID Master Record Identificati on (number). EPA’s system of recording and tracking submitted studies. MUP Manufacturing-Use Product

NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment

32NPDES National Pollutant Discharge Elimination System

NR Not Required

NOAEL No Observed Adverse Effect Level

OPP EPA Office of Pesticide Programs

OPPTS EPA Office of Prevention, Pe sticides and Toxic Substances PAD Population Adjusted Dose
PCA Percent Crop Area

PDP USDA Pesticide Data Program

PHED Pesticide Handler’s Exposure Data
PHI Preharvest Interval ppb Parts Per Billion

PPE Personal Protective Equipment ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the
EPA’s Cancer Risk Model

RAC Raw Agricultural Commodity

RED Reregistration Eligibility Document

REI Restricted Entry Interval
Rfd Reference Dose RQ Risk Quotient SCI-GROW Tier I Ground Water Computer Model

SAP Science Advisory Panel SF Safety Factor
SLN Special Local Need (Registrat ions Under Section 24c) of FIFRA

TGAI Technical Grade Active Ingredient

TRED Tolerance Reassessment and Risk Management Decision

USDA United States Department of Agriculture UF Uncertainty Factor
WPS Worker Protection Standard

33