TABLE OF CONTENTS 

 Page # 

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

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

 

III. Ecological Risk Assessment Problem Formulation......10 

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

V. Glossary of Terms and Abbreviations......................32 

2
I. PRELIMINARY WORK PLAN 

Urea Sulfate 

Introduction

The Food Quality Protection Act of 1996 amendments to the Federal Fungicide 

Insecticide and Rodenticide Act (FIFRA) mandated a new program: registration review. 

All pesticides distributed or sold in the United States generally must be registered by the 

United States Environmental Protection Agency (the Agency) based on scientific data 

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

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

program is intended to make sure that, as the ability to assess and reduce risk evolves and 

as policies and practices change, all registered pesticides continue to meet the statutory 

standard of no unreasonable adverse effects. Changes in science, public policy, and 

pesticide use practices will occur over time. Through the new registration review 

program, the Agency periodically reevaluates pesticides to make sure that as change 

occurs, products in the marketplace 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 years to determine whether it continues to meet 

the FIFRA standard for registration. The public phase of registration review begins when 

the initial docket is opened for each case. The docket is the Agency’s opportunity to state 

clearly 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. 

Anticipated Risk Assessment and Data Needs

The Agency anticipates conducting a comprehensive ecological risk assessment which 

will include an endangered species risk assessment. The Agency does not expect to 

conduct an additional human health risk assessment. At this time, the Agency does not 

anticipate that additional data will be needed. 

 Ecological Risk 

• A screening level ecological risk assessment 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 and 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 shallow 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 

3
risk assessment. The Agency will also consider the 1989 U.S. Fish and Wildlife 

Service Biological Opinion which discusses the use of urea sulfate on several 

vegetables, fruits, and 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, the 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 any additional ecological 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 Agency uses the ECOTOX database as its 

mechanism for searching the open literature for ecological effects information. 

ECOTOX integrates three previously independent databases – AQUIRE, 

PHYTOTOX, and TERRETOX – into a system which includes toxicity data 

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

terrestrial plants, and terrestrial wildlife.

 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. 

 

4
Timeline

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 3rd Quarter 2009 

Close Public Comment Period 4th Quarter 2009 

Phase 3: Registration Review Decision 

Open Public Comment Period for Proposed Reg. Review Decision 1st Quarter 2010 

Close Public Comment Period 2nd Quarter 2010 

Final Decision and Begin Post-Decision Follow-up 2010 

Total (years) 3 

Guidance for Commenters

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

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

information or data provided prior to issuing a final work plan for the urea sulfate case. 

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

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

Growers and other stakeholders are asked to comment on any trade irritant issues 

resulting from lack of Maximum Residue Levels (MRLs) or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible 

regarding the nature of the concern. Urea sulfate 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 90th percentile reported use rates (lbs. a.i./acre) from usage 

data—national, state, and county. 

4. Application timing (date of first application and application intervals) 

by use—national, state, and county. 

5
5. Typical application interval (days). 

6. Usage/use information for non-agricultural uses (e.g., golf course, 

athletic fields, ornamentals). 

7. Directly acquired county-level usage 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 90th percentile number of applications—county 

 d. total pounds per year—county 

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

area 

f. the years in which the pesticide was applied in the county/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 mortalities) 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 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 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 Data 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. 

6
II. 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—ethephon and glyphosate). 

• First product registered in 1987. 

• Not subject to reregistration; thus, no Reregistration 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 sulfuric 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 has been designated as GRAS for some 

uses when present in low concentrations. 

• Special Review and Reregistration Division (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 the urea sulfate docket.) 

• Urea sulfate can be used as an herbicide, desiccant, and harvest-aid on various 

crops and non-crops including: 

o Crops: Alfalfa, apples, barley, berries, 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 control, conservation reserve program, 

forestry site preparation, rights of way, ornamentals, nursery stock, 

Christmas tree plantings, pastures, fallow and reduced tillage systems. 

• Approximately 3,080,000 pounds of urea sulfate 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, shielded applicator, 

and aircraft. 

Recent Actions

• A TRED was completed June 14, 2005 and reassessed 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 accepted in February 2007. Entek was the 

technical registrant until the company was purchased by Griffin LLC. DuPont 

owns Griffin LLC. The revised technical label has DuPont as the sole technical 

registrant. 

Ecological Risk Assessment Status: Please refer to Section III of this document, 

Ecological Risk Assessment Problem Formulation, 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 pose a significant ecological risk. 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 directly 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 invertebrate toxicity. 

However, because of its fate properties, 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, freshwater 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 ecotoxicological effects of sulfuric acid. In 

addition, there are two sulfuric acid studies 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 shallow 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: 

8
Dietary (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 requirement 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 established 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 

9
III. ECOLOGICAL RISK ASSESSMENT 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 Effects Division’s (EFED) preliminary problem 

formulation for the ecological risk assessment to be conducted as a part of the 

Registration Review of the agricultural uses of urea sulfate as a desiccant and an active 

ingredient in herbicides. 

10
REGISTRATION REVIEW

ECOLOGICAL RISK ASSESSMENT

PRELIMINARY PROBLEM FORMULATION FOR: 

UREA SULFATE

PREPARED BY: 

Fred Jenkins, MS, Biologist 

Ibrahim Abdel-Saheb, Ph.D., Environmental Scientist 

Environmental Risk Branch 2 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

APPROVED BY: 

Dana Spatz, Acting Chief 

Environmental Risk Branch 2 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

11
STRESSOR SOURCE AND DISTRIBUTION

Urea sulfate (CAS Number 21351-39-3) is an active ingredient in herbicides and is used 

as a desiccant on agricultural crops. According to the Office of Pesticide Programs 

Information Network (OPPIN) two products are currently registered with urea sulfate as 

an active ingredient. These products are 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 herbicide 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 Office of Pesticde Programs Biological and 

Economic Analysis Division (BEAD). This analysis was based on data from the US 

Department of Agriculture’s National Agricultural Statistics Service (NASS). This 

analysis indicates that although urea sulfate is registered for use on a multitude of 

different crops, the actual usage of this 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 apparently acts via the 

catalyzation of hydrolysis of cellulose which results in the dissolution of the vegetative 

tissue. Urea sulfate readily dissociates to urea and sulfuric acid. Therefore, this 

preliminary problem formulation will evaluate the potential ecological effects of urea, 

and sulfuric acid individually. Both urea and sulfuric acid 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 Pesticide Programs Information Network): 

12
Table 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, Cherry, Nectarine, Olive, Peach, 

Pear, Plum, Plumcot, and Prune 

Tree Nuts Almond, Beechnut, Brazil Nut, Butternut, Cashew, 

Chestnut, Filbert, Hickory 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 (All), Broccoli (All), Brussels 

Sprouts, Cabbage (All), Chinese Cabbage, 

Cantalope, Cauliflower, Casaba Melon, Celery, 

Chard Swiss, Collard, Crenshaw 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 Estimates 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 < 1indicates less than 2.5 percent of crop and 1 percent of crop respectively is 

treated. 

 

13
INTEGRATION OF AVAILABLE INFORMATION

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 Decision (RED) document for Mineral Acids 

(The mineral acids include four different active ingredients including sulfuric 

acid, the herbicidal active ingredient of urea sulfate. Each of the active 

ingredients was evaluated independently 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 

ECOLOGICAL EFFECTS

TOXICITY STUDIES

Registrant Submitted Studies for Urea Sulfate 

The registrant submitted studies include one fish acute toxicity study, an acute oral rat 

toxicity test, two avian acute dietary studies, one aquatic plant toxicity study, and three 

terrestrial plant toxicity studies including 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 testing fish, birds, and mammals demonstrated that urea sulfate 

is slightly to practically 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 EC50 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 study 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 anymore than 14% among any of the species 

tested. The algal toxicity study demonstrated a Selenastrum capricornutum EC50 of 11.5 

ppm. The results of the avian simulated field study demonstrated that birds exposed to 

14
spray applications of urea sulfate displayed significant eye and foot damage that may be 

pronounced for birds exposed to direct applications of undiluted urea sulfate. The results 

also concluded that diluted 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 invertebrates based on the 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 invertebrates. 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 (see below, Registrant Submitted Studies for Urea) and 2) sulfuric acid is 

expected to readily dissociate into sulfate ions which are innately nontoxic. 

Registrant Submitted Studies for Urea 

There are four registrant submitted ecotoxicity studies for urea. These include two 

freshwater fish acute toxicity studies, one freshwater invertebrate study, and one avian 

acute dietary toxicity study. These studies indicate that urea is practically nontoxic to 

freshwater fish, freshwater invertebrates, and birds (birds practically 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 ingredient. 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). Furthermore, the available registrant submitted studies 

testing urea sulfate contained 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 demonstrated by the studies evaluated thus far and the 

available registrant submitted studies testing urea sulfate, EFED does not believe it 

necessary to require additional toxicity data for sulfuric acid. 

15
Table 4. Results Preliminary ECOTOX Database Search 

Species 

(Common name) 

Test 

Duration 

(Days) 

LC50 (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) 

LC50 (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 

INCIDENT REPORTS

According to Office of Pesticides Program Ecological Incident Information System 

(EIIS), there is one incident in Kern County California reportedly 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 nitrate, manganese nitrate. The Lorsban tank 

mix was applied to a tangelo crop on April 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 other ingredients in the tank mixture caused the 

ridging. 

16
EXPOSURE CHARACTERISTICS

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 reviews may be found below. 

Biodegradation is expected to be the major fate process in the aquatic ecosystem. Various 

screening studies have demonstrated that urea can biodegrade readily with the release of 

CO2 and ammonia. The rate of biodegradation generally decreases with decreasing 

temperatures; under cold winter-like conditions, biodegradation may be relatively slow 

(0-6% per day). The presence of naturally-occurring phytoplankton increases the 

degradation rate because phytoplankton uses urea as a nitrogen source and because urea 

is decomposed by phytoplankton via photosynthesis. 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 0C, indicates urea will exist 

in both the vapor and particulate phases in the ambient 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 hydrolysis 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 CO2 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 irradiation 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 adsorption was measurable in five of the soils; 

in the sixth soil (36.5% organic carbon), a KOC of 8 can be determined from the measured 

Freundlich isotherm. 

BCF values of 1 and <10 suggest bioconcentration 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 (DWLOCs) were not calculated for urea 

(http://www.epa.gov/pesticides/reregistration/REDs/urea_tred.htm). 

In conclusion, available data from literature reviews show that urea degrades rapidly in 

most soils. Soil adsorption studies have demonstrated that urea adsorbs very weakly to 

17
soil; however, because urea degrades rapidly, leaching to groundwater in appreciable 

amounts is not expected. Ultimate urea degradation produces ammonia and CO2 .

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 submitted, one being a simulated ephemeral pond study, 

consisting of 5 gallon buckets, 6 inches of soil (8 various types) 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 difference between the ponds treated with the 50 

gal/A, and the ponds (buckets) treated with 100 gal/A. All treated buckets plummeted to a 

pH of approximately 2.5 within the first day of treatment. One soil indicated that the pH 

did not go higher than 5 until 21 days postapplication. 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 inches 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 concentrations of urea sulfate, urea or sulfuric acid 

in surface or groundwater. 

CHARACTERISTICS OF ECOSYSTEMS POTENTIALLY AT RISK

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 ions 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 occurrences in the environment. 

For urea sulfate and pesticides in general, the ecosystems at greatest risk are those in 

close proximity to the use areas. These would include agricultural fields 

(surrounding non-agricultural terrestrial 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 column, sediments, and pore water are all 

compartments of concern. 

18
Organisms 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 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. 

ASSESSMENT ENDPOINTS

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

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

identifying the valued attributes of the environment that are considered to be at risk; and 

2) operationally defining the assessment endpoint in terms of an ecological entity (i.e., a 

community of fish and aquatic invertebrates) and its attributes (i.e., survival and 

reproduction). Therefore, selection of the assessment endpoints is based on valued 

entities (i.e., ecological receptors), the ecosystems potentially at risk, the migration 

pathways of pesticides, and the routes by which ecological receptors are exposed to 

pesticide-related contamination. The selection of clearly defined assessment endpoints is 

important because they provide direction and boundaries in the risk assessment for 

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

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

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

such as urea sulfate. 

The most sensitive toxicity endpoints are used from surrogate test species to estimate 

treatment-related direct effects on acute mortality and chronic reproductive, growth and 

survival assessment endpoints. Toxicity tests are intended to determine effects of 

pesticide exposure on birds, mammals, fish, terrestrial and aquatic invertebrates, and 

plants. These tests include short-term acute, sub-acute, and reproduction studies and are 

typically arranged in a hierarchical or tiered system that progresses from basic laboratory 

tests to applied field studies. The toxicity studies are used to evaluate the potential of a 

pesticide to cause adverse effects, to determine whether further testing is required, and to 

determine the need for precautionary label statements to minimize the potential adverse 

effects to non-target animals and plants. The following is a summarization of the most 

sensitive endpoints from the available ecotoxicity data. 

Urea Sulfate Most Sensitive Endpoints

Birds 

The acute toxicity studies demonstrated that urea sulfate is practically non-toxic to birds. 

(studies demonstrated no mortalities to test birds). Thus, there are no acute toxicity 

endpoints for birds. 

19
Mammals 

The most sensitive mammalian acute oral toxicity endpoint was a rat acute oral LD50 of > 

5000 mg/kg. 

Fish 

The most sensitive fish acute toxicity endpoint for urea sulfate is a Three spine 

Stickleback LC50 of 80 ppm (ACC072861). 

Aquatic Invertebrates 

Urea sulfate toxicity endpoints have not been determined for aquatic invertebrates. 

Aquatic plants 

The most sensitive algal toxicity endpoint for urea sulfate is a Selenastrum 

capricornutum EC50 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 EC50 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 seed germination and seedling emergence 

studies demonstrated that urea sulfate had 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 invertebrates, or birds because 

urea is practically nontoxic to all these organisms (LC50 and EC50 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 ecotoxicological effects of sulfuric acid. 

CONCEPTUAL MODEL

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

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

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

ecological exposure pathway to be complete, it must have a source, a release mechanism, 

20
an environmental transport medium, a point of exposure for ecological receptors, and a 

feasible route of exposure. 

The conceptual model (Figure 1) depicts the potential pathways for ecological risk 

associated with urea sulfate, urea and sulfuric acid. The conceptual model provides an 

overview of the expected exposure routes for organisms within the urea sulfate action 

area. For terrestrial organisms, the major route of exposure considered is the dietary 

route; consumption of food items such as plant leaves or insects that have urea sulfate 

residues as a result of spraying, drift, and volatilization. For aquatic animal species, the 

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

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

terrestrial and wetland (riparian) plants, while aquatic plants may be exposed via direct 

uptake and adsorption. Estimated exposure concentrations for all organisms are obtained 

through the use of several Agency exposure models. 

RISK HYPOTHESIS

Based on an examination of the physical/chemical properties of urea sulfate, the fate and 

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

developed that represents the possible relationships between the stressor, ecological 

receptors, and the assessment endpoints. EFED predicts that once urea 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 primary 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 concentration, be subject to changes in pH. The 

change in pH could potentially pose an adverse threat to the inhabitants of these water 

bodies. Secondly, EFED predicts terrestrial organisms that come in direct contact with 

the sulfuric acid may be at risk of experiencing the corrosive effects this chemical can 

have on tissue. 

21
FIGURE 1. ECOLOGICAL CONCEPTUAL DIAGRAM FOR UREA 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 

22
ANALYSIS PLAN OPTIONS

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 Assessment Process in the Office of Pesticide 

Programs, U.S. Environmental Protection Agency” (“Overview Document”) (January 

2004), and will address obligations under Section 7 of the Endangered Species Act. 

A screening level ecological risk assessment has never been conducted for urea sulfate. 

The only type of ecological assessments that the Agency has conducted for the 

agricultural use of urea sulfate are “hazard assessments.” These types of assessments 

were conducted prior to the Agency’s policy implementing that “ecological risk 

assessments” be conducted to assess the potential 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-target organisms. The focus of an ecological risk assessment 

is on both the toxic effects of a pesticide to non-target organisms and the potential routes 

of the pesticide’s exposure to non-target organisms. In addition to addressing a 

pesticide’s toxic effects and potential routes of exposure, an ecological risk assessment 

addresses the uncertainties 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 these assessments as a resource for 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 and Expansion of Geographic Areas from Previous Label 

U.S. EPA Ecological Effects Branch, September 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 could lower the pH of very small and shallow 

water bodies with low buffering capacity, 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 

23
document may be useful, other portions could be outdated and no longer applicable due 

to changes in labels, use patterns, etc. 

ANTICIPATED DATA NEEDS

Although the guideline ecotoxicity data set is not complete for urea sulfate and sulfuric 

acid, the Agency does not foresee requiring any additional ecological effects or 

environmental fate studies prior to conducting the planned assessments (see Table 5). 

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

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

for searching the open literature for ecological effects information. ECOTOX integrates 

three previously independent databases – AQUIRE, PHYTOTOX, and TERRETOX – 

into a system which includes toxicity data derived predominately from the peer-reviewed 

literature, for aquatic life, terrestrial plants, and terrestrial wildlife, respectively.

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 toxic concern to aquatic 

invertebrates based on the 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 invertebrates. 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 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). 

Furthermore, the available registrant submitted 

studies testing urea sulfate contained up to 49% 

sulfuric acid, and these studies showed no 

concerns for acute avian toxicity. 

24
OTHER INFORMATION NEEDS

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

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

much interested in obtaining the following information: 

1. 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, application intervals, and maximum number of 

applications per season 

f. geographic limitations on use 

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

relevant crops) 

3. use history 

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

national, state, and county 

5. application timing (date of first application and application intervals) by 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 data (not derived from state level data) 

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

b. percent crop treated – county 

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

d. total pounds per year – county 

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

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

9. typical interval (days) 

10. state or local use restrictions 

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

and mammalian mortalities) not already reported to the Agency 

12. monitoring data 

The analysis plan will be revisited and potentially revised depending upon the data 

available in the open literature and the information submitted by the public in response to 

the opening of the Registration Review docket. 

25
IV. 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: Registration 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 Reregistration Division (7508P) 

Attached is the human health scoping/problem formulation document to support the registration 

review of the herbicide and desiccant, 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 sulfate and determined whether changes in 

science policy or deficiencies 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 quantities during normal metabolism. Urea has been 

26
designated by FDA as Generally Recognized 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 GRAS 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 adduct currently has an exemption from the 

requirement of a tolerance when used as an herbicide 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, Nectarine, 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), Pummelo, Tangelo, Tangerine, Tangors 

Vegetables: Asparagus, Beans (All), Broccoli (All), Brussels Sprouts, Cabbage (All), 

Cabbage (Chinese), Cantaloupe, Cauliflower, 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), Pepper (All), Persian Melon, Potato, 

Pumpkin, Rape Greens, Rhubarb, Spinach (All), Squash (Summer and 

Winter), Sugarbeet, Tomatillo, Tomato, Watermelon 

Vines: Grapes 

Tropical Fruits: Avocado, Banana, Coffee, Dates, 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; Conservation 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 desiccant (each current label actually lists this 

active ingredient as 1-aminomethanamide dihydrogen tetraoxosulfate). This active 

ingredient was first registered in 1987. 

27
The Agency has determined that urea sulfate readily degrades to urea and sulfuric acid 

and/or sulfate ions in the environment 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 since the last human health risk assessment was 

completed for the TRED in 2005. A comprehensive search of the open literature was 

not done primarily because a screening Google search (Google Scholar) and a Science 

Direct search indicated little new information relevant to the human health risk 

assessment has been published on this herbicide that had not already been considered in 

previous assessments. 

The data requirements for the higher tier toxicity studies have all been waived by the 

Agency, and there are no repeated dose toxicity studies available for urea sulfate. 

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

28
Table 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 with 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 adverse effects that would be expected in 

infants and children for urea sulfate. For urea, animal studies provide no evidence of 

developmental or teratogenic effects. In an aqueous 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 unnecessary, 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 REDs and TREDs for these constituent products, 

the Agency has determined that only a qualitative 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 sulfate (or at least for the consumption of 

products containing urea sulfate as the sole active ingredient). 

29
Section 4. Aggregate and Cumulative Exposure 

There are no residential uses for urea sulfate. No aggregate exposure assessment is 

needed, given the lack of human health concerns associated with exposure to urea sulfate, 

as well as its constituent products (urea and sulfuric acid and/or sulfate ions). 

EPA does not have, at this time, available data 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 mechanism of toxicity, 

EPA has not made a common mechanism of toxicity finding as to urea sulfate and any 

other substances, and urea sulfate does not appear to produce a toxic metabolite produced 

by other substances. 

Section 5. Occupational Exposure 

As mentioned above, the Agency has determined that urea sulfate readily breaks down 

into urea and sulfuric acid and/or sulfate ion in the environment and in the human body. 

Assessments performed on both these compounds 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 containing urea sulfate would 

not present a human health hazard to occupational workers or the general public. 

Section 6. Anticipated Data Needs 

The Agency does not expect to require any additional data for urea sulfate. There are 

several unreviewed product chemistry studies which will be reviewed later in the process. 

Section 7. Tolerances/Exemptions from 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

30
Section 8. Overall Conclusions 

The qualitative risk assessments for dietary and occupational exposure 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 Reassessment Eligibility Decision: Urea Sulfate 

31
V. 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 Surveys 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 

LC50 Median Lethal Concentration. A statistically derived concentration 

of a substance that can be expected to cause death in 50% of test 

animals. It is usually expressed as the weight of substance per 

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

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

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

administered by the route indicated (oral, dermal, inhalation). It is 

expressed as a weight of substance per unit weight of animal, e.g., 

mg/kg. 

LOC Level of Concern 

LOAEL Lowest Observed Adverse Effect Level 

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 Identification (number). EPA’s system of 

recording and tracking submitted studies. 

MUP Manufacturing-Use Product 

NA Not Applicable 

NAWQA USGS National Ambient Water Quality Assessment 

32
NPDES 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, Pesticides 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 

Q1* 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 (Registrations 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