E' ph-#4.-Q)cpr_ :~,oDs ..rs 63 

UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Submission 

For Fulfilment of Data Requirements 

for Urea, Reaction Products with Formaldehyde 

Under TSCA Section 4 

1. Chemical Name: Urea, reaction products with formaldehyde 

2. CAS Number: 68611-64-3 

3. Industry Sponsor: The Fertilizer Institute 

William Herz 

820 First Street NE, Union Ctr Plaza Ste 430 

Washington, DC 20002 

Tel : (202) 515-2706 

I 9. Date of Submission: July 2007; Revised March 2008 

10. Comments: Urea, reaction products with formaldehyde is not manufactured 

or processed for distribution in commerce as chemical substance 

per se and, relative to the fertilizer industry, has no commercial 

purpose separate from the substance mixture or article of which 

it may be a part (40 CFR § 710.4(d)) . 

Urea, reaction products with formaldehyde (UF) is primarily 

methylene diurea (MDU, CAS No 13547-17-6) and relies on 

data presented for Urea (CAS 57-13-6; Screening Information 

Data Set (SIDS) of OECD High Production Volume Chemicals 

Programme (1994; see attached documents). Both UF, including 

MDU and Urea are enzymatically hydrolyzed to ammonia and 

carbon dioxide in the environment and in mammalian systems. 

Isopropyl methvlenediurea (CAS No. 6104-30-9; chemical name 

1,1'-(2-methvluropane-1,1-divl)diurea) is considered to be an 

analog of MDU. The only difference between them is the 

substitution of isopropyl for H on the methylene carbon . 

p. .1 

trau.~"~n 

T~1 r7l 

0 

c.~ 

CONTAINS NO CBI 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

CONTENTS 

1 IDENTITY . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 5 

1 .1 Identification of the Substance . . . . . . .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 5 

1 .2 Physico-Chemicalproperties . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .I - 

2 GENERAL INFORMATION ON EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6 

2 .1 Environmental Exposure and Fate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 7 

2.1 .1 Sources of Environmental Exposure . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . .7 

2.1 .2 Photodegradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 7 

2.1 .3 StabilityinWater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . , . 

2 .1 .4 Stability in Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . .~-

2.1 .5 Transport between Environmental Compartments . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .~ 

2.1 .6 Biodegradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . .8 

3 HUMAN HEALTH HAZARDS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . .-9 

3.1 Effects on Human Health . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . 9, 

- 3 .1 .1 Toxicokinetics, Metabolism and Distribution . ... . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

3 .1 .2 Acute Toxicity.. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ~ _. 

3 .1 .3 Repeated Dose Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . 9 

3 .1 .4 Mutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . ... . 1~1 

3 .1 .5 Toxicity for Reproduction . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . I), 

4 HAZARDS TO THE ENVIRONMENT . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . ~ 

4.1 Aquatic Effects . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . " 

5 RECOMMENDATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .12 

6 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . .. . . . . . . . . .13 

-FDeleted - . 6 

- Dele,betl :7 

Deleted: 7 

Deleted: 7 

"l 

Deleted: 8 

Deleted: 8 

Deleted: 8 

Deleted. 8 

Deleted: to 

Deleted: 11 

, DeleEed:ll 

, DeleEed:ll 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Tables 

Table 1 Summary of physico-chemical properties: MDU . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .6 

Table 2 Summary of acute toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. .. . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . 9 

Table 3 Summary of repeated dose toxicity . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . " . .. - -. - Delebed : 10 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Submission 

for Fulfilment of Data Requirements for 

Urea, Reaction Products with Formaldehyde 

Under TSCA Section 4 

1 IDENTITY 

1.1 Identification of the Substance 

CAS Number: 68611-64-3 

Primary component: Methylene diurea (MDU) 13547-17-6 

Molecular Formula: Unknown, Variable, Complex, Biological (UVCB) 

CH4N20.CH20 

W99 

(MDU = C3H8N4O2) 

Structural Formula: 

NH, 

NH: 

Primary component, MDU 

Molecular Weight: NA 

(MDU = 132.12) 

Synonyms : Formaldehyde, urea adduct 

UF 

1.2 Physico-Chemical properties 

Urea, Reaction Products with Formaldehyde (UF) is an Unknown, Variable, Complex, Biological 

substance. The physical chemical properties of this mixture have not been determined. The physical 

chemical properties of the major component of UF are provided. 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Table 1 Summary of physico-chemical properties : 1VII)U 

Property Value Reference 

Physical state solid 

Melting point 212-214°C Hays and Haden (1966) 

Boiling point Not applicable 

Relative density No data 

Vapour pressure Not applicable 

Water solubility 25 g/i Hays and Haden (1966) 

Partition coefficient noctanoUwater (log value) 

-3 .01 Epiwin, v3.20 

2 GENERAL INFORMATION ON EXPOSURE 

Urea, reaction products with formaldehyde (UF) is not a commercial product for the members of 

The Fertilizer Institute (TFI). Typically, during production, 95% of the domestic urea producers, 

condition urea with a formaldehyde-based additive . In the urea production process, formaldehydebased additives (FBA) are injected into molten urea or a hot urea solution. At process temperatures 

(- 280°F), formaldehyde reacts to form methylenediurea (MDU, 13547-17-6) and water. MDU is 

used as a conditioning agent, which reduces solids caking during storage and urea dust formation 

during transport and handling (TFI, 2007). The final product (fertilizer) contains unreacted urea, 

methylenediurea, methylenetriurea and longer chain polymers . Free formaldehyde is generally not 

present in UF Table 2). Recent analysis of urea fertilizers indicate that of the ca 19. 8 million short 

tons of urea fertilizer produced and imported in the US nearly 99 percent (ca 19. 6 million short 

tons) has been shown to contain 0-0.5 npm free formaldehyde . Only solid urea fertilizer has been 

shown to contain free formaldehyde, at a range of 0-18 . 7 pam MDU is the principle compound 

formed when the formaldehyde additive reacts with hot urea (USEPA, no date specified; Murray et al ., 1982). Current levels of MDU in fertilizer grade urea are 1.3-2 .7%. 

Table 2 Types of Urea and Free Formaldehyde Levels (Fertilizer Year Endine June 30 

2_006) 

-Analv ~ 

Type of Urea US Production Free Formaldehyde, Explanation 

Fertilizer and import 

volume, 

Million short 

tons 

Dam 

Urea Ammonium 10 .1 M Q Urea in liauid form does not have 

Nitrate (UAN 

Solutions 

formaldehyde or FBA added 

Urea, solid (prill or - 0.2 M * Variati d 

granular) 0-18.7 on appears to epend on 

manufacturing process and starting 

compound 

Urea, solid (nrill or -V 8 M Va i ti 

granular) 0-0.5 r a on annears to depend on 

manufacturing process and starting 

comnound 

Technical Grade Urea 1 .45 M o Technical erade urea also does not 

a!1 o. ., .. ED A ... 

_ 

have FBA added 

ethod 8315A with a detection limit of! ppm. 

- - - Fonnatted Table 

Fonnatbed: Normal, Space Before: 

6 pt 

JtFormatl:ed: Normal, Space Before : 

6 pt 

6 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

~ 

,Some 

urea fertilizer manufactures r~orted the manufacture and import of biuret and urea reaction_ 

products associated with the manufacture and import of urea fertilizer in TSCA Inventory Update 

Rule (IUR) Form U submissions including the 2002 reports for activities in 2001- EPA Form 

Numbers 6511017 and 65011017. In 2003, TFI petitioned EPA for a partial reporting exemption for 

fertilizers and certain fertilizer materials including biuret and urea reaction products from inventory 

update reporting requirements proposed for 2006 and beyond. In November 2003 and December 

2004, EPA issued letters to TFI concluding that biuret and urea reaction products with 

formaldehyde are "impurities" as defined in 40 CFR. § 720.3 and therefore were not subject to 2006 

IUR reporting. The applicable provision of the now final regulation is § 710.50(c) which defines 

manufacturing a chemical substance "in a manner described in § 720.30(g) or (h)" of the regulations 

as an activity for which reporting is not required. 

A similar regulation, § 710.30(c), applies to 2002 IUR reporting. Some of the urea fertilizer 

manufacturers 2002 IUR reports included chemical substances for which it is now clear, based on 

EPA's November 2003 and December 2004 interpretation letters, that reporting was not required . 

These urea fertilizer manufacturers revised and resubmitted 2002 Form U Reports removing biuret 

(CAS No. 108-19-0) and urea reaction products with formaldehyde (CAS No. 68611-64-3). 

MDU is the largest component of the methyleneurea polymers found in ureafotm fertilizers and is 

used as a structural analogue to represent the smaller percentage of larger polymeric methyleneurea 

polymers as described by CAS No 68611-64-3. In addition, MDU (and other UFs) is degraded in 

the environment to urea, ammonia and carbon dioxide (Jahns and Kaltswasser, 2000; Kaempffe and 

Lunt, 1967). For example, MDU degrades ca. 90% in 14 days (Katz and Fassbender, 1966). 

Biode~4radation data for 1,1'2-(2-methylpropane-l .l-diyl)diurea (CAS No 6104-30-9), an analog of 

MDU, are available throuQli the MITI database (2002) . The results indicate the analoa biodegrades 

78 - 100%, by indirect and direct analysis . respectively, over -1 weeks. ,From the biodegradation _ 

pen-,pective, the analog is . similar but in theorv might be slower to degrade than MDU_piven its -_, 

.- - - --- ---- .. .._ 

substitution (of isopropyl for H) on the methvlene carbon. Data - were not located regarding the 

degradation of UF in the mammalian gut; structure activity analysis in combination with 

information regarding degradation by microorganisms suggests UF will readily degrade to urea (and 

then to ammonia and carbon dioxide) . Data from urea UNEP Publications, date not specified) are 

used to provide additional information for UF. As stated in the UNEP document, "urea is an 

important endogenous product of mammalian metabolism. Urea appears to cause little or no toxicity 

to most mammalian species (ruminants are an exception) and humans at reasonable dose levels. 

Further, the EPA has indicated that urea poses no risk concerns within the limits of the existing 

tolerance exemptions (_http ://www .epa.eov/onnsrrdl/rereQistration/urea/) , urea is approved for 

several human therapeutic uses (httn://216 .239 .51.104/search?q=cache:n1264Z8FFIJ:www.fda.eov/cder/o¢d/rid/12154s24.ndf+FDA+cateeorv+C+urea&h1=en&ct=clnk&cd 

=1&gl--us ) and is considered "Generally Recognized As Safe" (GRAS) as affirmed by the U. S. 

Food and Drug Administration for use in food (21 C.F.R. § 184.1923 Urea. Title 21 - Food and 

Drugs). 

2.1 Environmental Exposure and Fate 

2.1 .1 Sources of Environmental Exposure 

2.1 .2 Photodegradation 

The overall OH Rate Constant was = 1 .97 E-12 cm3/molecule-sec with a half-life = 0.5 days 

(Epiwin, v3 .20, RL=2). 

- Delebed: y J 
UREA, REACTION PRODUCTS WITH FORMAI.DEHYDE 

2.1 .3 Stability in Water 

Hydrolysis studies were not available. Modeling indicates that the hydrolysis rate will be extremely 

slow (tl/2 > 1 year) (Epiwin, v3 .20, RL=2). 

2.1 .4 Stability in Soil 

The rates of nitrification of methylenediureas were investigated in soil (Hays and Haden, 1966). 

Urea reached 80% conversion to nitrate after 12 days, MDU nitrification was slower (about 30% in 

12 days; 90% in 14 days) and dimethylene diurea (DDU) nitrification was slower still (about 15% 

in 12 days; 50% in 14 days). In a second experiment, water was added to the soil 10 days before 

the addition of the test substances to allow the build-up of nitrifying bacteria . The induction period 

was nearly eliminated for urea (100% in 8 days), while MDU and DDU required 8 or 9 days to 

begin production of significant amounts of nitrate (after 16 days about 90% for MDU and about 

30% for DDU). Similar results were reported in which 85% nitrification of MDU and DDU was 

observed in three weeks; 68% of trimethylene tetraurea and <5% tetramethylene pentaurea was 

observed in the same period (Kaempffe and Lunt, 1967; Long and Winsor, 1960). 

2.1 .5 Transport between Environmental Compartments 

Ureaforms such as MDU and DDU have decreased rates of leaching compared to urea (Hays and 

Haden, 1966). About 90% of the applied ureaform was retained in soil; about 10% of the applied 

urea was retained in soil . With the more drastic leaching procedure (procedure 2) the retention of 

ureafonn nitrogen was reduced to 76%, due to low solubility . 

The EQC Level III Fugacity model (Epiwin, v3 .20, RL=2) was used to evaluate the fate, transport 

and distribution of MDU between environmental matrices . Level III fugacity modelling, using 

loading rates of 1000 kg/h each for air, soil and water, shows the following percent distribution 

when it is released simultaneously to all three compartments : Air = 4.12E-11%; Soil = 60.9 ; Water 

= 39%; Sediment = 0.713%. 

2.1 .6 Biodegradation 

Nitrogen content was made the limiting factor in the test media in a modified Warburg test in which 

MDU, Dimethylentriurea, Trimethylenetetraurea, and the low, intermediate, high and total 

combined molecular weight fractions of ureaform were tested (Katz and Fassbender, 1966, RL=2). 

Increases in chain length decrease biodegradability ; MDU was ca. 80 and 90% degraded in 8 and 14 

days, respectively. Dimethylenediurea was degraded ca. 70% degradation in 8 and 14 days. 

Trimethylenetetraurea degraded ca. 40 and 60% in 8 and 14 days, respectively. The low MW 

fraction degraded 100% in 11 days; the intermediate MW fraction degraded 70% in 11 or after 14 

days, the high MW fraction degraded <10% in 11 days and ca . 10% after 14 days and the combined 

MW fractions degraded ca . 66% after 14 days. In garden soil, the microbial degradation of 7.5mM 

MDU as the sole source of fixed nitrogen was followed at 26C (Jahns and Kaltswasser, 2000, 

RL=2). 100% of the MDU was degraded by 4 days. Epiwin modeling indicates MDU is likely to 

be biodegradable (Epiwin, v3.20, RL=2). In a modified MITI test (OECD 301C), 1,1'2-(2-

methylpropane-l,l-diyl)diurea (CAS No 6104-30-9), an analog of MDU, biodegradation rates of 

78% and 90% to 100°/o were achieved by indirect (BOD: NH3) and direct analysis (TOC and 

HPLC), resaectively, over 4 weeks. From the biodeeradation perspective, the analog is similar but 

in theorv might be slower to degrade than MDU given its substitution (of isopropyl for H) on the 

methyl _ene_ carbon . 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Urea is ultimately biodegradable in inherent biodegradability test (OECD TG 302 B). In semicontinuous activated sludge (SCAS) urea is biodegraded on the average of 93-98% in 24-hour 

cycle. The main mode of degradation is enzymatic mineralization. In soil and water urea is expected 

to biodegrade fairly rapidly to ammonia and bicarbonate if temperature is not too low. Ammonia is 

a volatile gas in alkaline solutions. In natural waters, most ammonia appears in the form of 

ammonium, from which nitrogen is oxidized IRPTC Data Profile Identifiers, Physical and Chemical 

properties 3 as the result of bacterial action, forming nitrite and nitrate. According to US-EPA 

PCGEMS-model hydrolysis of urea is expected to be extremely slow (TI/2 > I years) (UNEP, date 

and RL not specified) . 

3 HUMAN HEALTH HAZARDS 

Data from urea (UNEP Publications, date not specified) are used to provide human health hazard 

information for UF. 

3.1 Effects on Human Health 

3.1 .1 Toxicokinetics, Metabolism and Distribution 

Data were not located regarding the degradation of UF in the mammalian gut; structure activity 

analysis in combination with information regarding degradation by microorganisms suggests UF 

degrades to urea (and then to ammonia and carbon dioxide) . These hydrolysis products can then be 

used to synthesize amino acids. The complete hydrolysis and deamination of protein involves 

numerous enzymes. 

Urea is extremely soluble in water and oral doses are rapidly absorbed and distributed in humans. 

Urea is a normal human body constituent and is constantly being produced through amino acid and 

protein metabolism where urea is formed through a cyclic mechanism. 

3.1 .2 Acute Toxicity 

The acute toxicity of UF has not been studied. 

The acute toxicity by urea is well delineated by the oral route. Toxicity is low in mammals other 

than ruminants, especially cattle, and sheep, in which the rumen micro-organisms contain urease 

activity and metabolize urea to ammonia at a high rate . In mice and rats, urea is of low toxicity even 

by the subcutaneous and intravenous route (UNEP, date and RL not specified) . Examples of 

specific toxicity values published for urea are provided for comparison in Table 2. 

Table 2 Summary of acute toxicity : Urea 

Species Value (mg/kg bw) RUReference 

Urea 

Sheep Oral LD50 = 510 Not specified/FDA, 1978 

Rat Oral LD50 =14300 

(M); = 15000 (F) 

Not specified/Sato et al., 1978 

3.1 .3 Repeated Dose Toxicity 

Repeated dose toxicity studies with UF have not been conducted. 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Repeated dose studies were located for urea which was not presented in the UNEP document. Five 

groups of steers were fed a high-roughage, low-concentrate wintering ration in dry lot for 84 days 

(Berry et al ., 1956; RL=2). The basal ration was made up of 36.5% Atlas silage (hay basis), 24% 

cottonseed hulls, 6% alfalfa leaf meal, 11% blackstrap molasses, and from 13% to 20% milo grain 

and 1% minerals (bonemeal and salt). The crude protein supplements used were 7.5% cottonseed 

meal (Group 1), 1% feed-urea (Group 2), 1% crude biuret (Group 3), 1 .5% a mixture of crude biuret 

and feed-urea (Group 4), and 1 .25% of a urea-fatty acid complex (Group 5) . The total intake of 

each group was adjusted to that of the lowest consuming group. This was accomplished by hand 

feeding. Each ration was calculated to supply equal amounts of dry matter, total digestible 

nutrients, and except for Group 4, protein equivalent. Group 4 was 1 .4% higher in crude protein 

equivalent. The urea-fatty acid complex was 75% urea and 25% cottonseed foots. Animals were 

observed for signs of toxicity and average weight gain was calculated at study termination. The 

average gains made by the control group and the urea group (Group 2) were not significantly 

different. However, when the urea was replaced with the crude biuret (Group 3), a significantly 

lower gain resulted . This group also consumed the least feed and therefore, restricted the intake of 

the other groups . When additional urea was included with the crude biuret (Group 4), the average 

gain was statistically significantly. Thus, simply adding urea overcame the adverse effects of 

biuret. Although Group 4 gained slightly more than the group fed urea alone (Group 2), the 

difference was not significant. The increase in daily gain may suggest that contrary to the results 

obtained with Group 3, the biuret nitrogen was utilized to some extent by the rumen bacteria. The 

group fed urea-fatty acid complex (Group 5) gained essentially the same as the urea fed group 

(Group 2) . Based on this single study it appears that urea fed as a urea-fatty acid complex is 

efficiently utilized . 

No well-conducted repeated dose toxicity studies on urea were located (UNEP, date and RL not 

specified) . Chronic toxicity and carcinogenicity screening studies in mice and rats fed with 4500, 

9000 or 45000 ppm in diet (up to about 6750 mg/kg body weight/day for mice and about 2250 

mg/kg body weight/day for rats) did not uncover any treatment-related toxic syndromes in the 

various organs studied (Fleischman et al ., 1980, RL not specified). Neither was any weight 

depression noted at terminal necropsy for animals of either sex or species at any dose levels. Thus 

the NOAELs were about 6750 mg/kg body weight/day for mice and about 2250 mg/kg body 

weight/day for rats . 

Repeated dose toxicity studies with rats by skin application over 4 weeks and 25 weeks were 

conducted using urea ointment at 10%, 20% and 40% concentrations, and no consistent treatmentrelated toxic effects were found. The ointments were applied on a 20 cm2 area of the back skin but, 

unfortunately, the quantities of urea applied were not given. Therefore no value for NOAEL by 

dermal route can be determined. It can be concluded, however, that the repeated dose toxicity of 

urea by dermal route was low (UNEP, date and RL not specified) . 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Table 3 Summary of repeated dose toxicity: Urea* 

Study Design Result RL/Reference 

Pullets; diet: 0, 1 % urea, 1 % biuret, or soybean oil - NOAEL = 1 % urea 2/ Berry et al., 1956 

exposure time not specified 

Lambs; diet: 7.5% cottonseed meal (Group 1), 1% NOAEL =1% urea 2/ Berry et al ., 1956 

cottonseed meal plus 1% urea feed-urea (Group 2), 

1% cottonseed plus 1% crude biuret (Group 3) - 84 d 

Steers ; diet: 7 .5% cottonseed meal (Group 1), 1% NOAEL =1 %urea 2/ Berry et al ., 1956 

feed-urea (Group 2), 1% crude biuret (Group 3), 1 .5% 

a mixture of crude biuret and feed-urea (Group 4), 

and 1 .25% of a urea-fatty acid complex (Group 5) - 

84 days 

Rat or mouse; diet : 4500, 9000 or 45000 ppm - 12 m NOAEL (mouse) ca. = Not 

6750 mg/kg bw/day; (rat) specified/Fleischman 

ca . = 250 mg/kg bw/day et al., 1980 

Rat ; dermal : 10%, 20% and 40% - 4 or 25 w NOAEL not identified . Not specified/ Not 

Repeated dose toxicity specified; UNEP, date 

"low" not specified 

(*) The Berry et al ., 1956 studies presented in Table 2 were not included in the SIDS documents for Urea. 

3.1 .4 Mutagenicity 

Mutagenicity studies were not located for UF. Urea has been tested for mutagenicity in vitro and in 

vivo . The mechanism of genotoxicity of urea is probably non-specific (e.g . difference in osmotic 

pressure across the cell membrane) (UNEP, no date specified) . Similar effects are expected for UF. 

In vivo Studies 

Urea was clastogenic for mammalian cells in vivo but the interpretation of this clastogenic effect is 

limited by the usage of a single extremely high dose level (Chaurasia and Sinha, 1987, RL not 

specified) . 

In vitro Studies 

Urea has been negative in several appropriately conducted bacterial mutagenicity tests (Ishdate, et 

al, 1981; Shimizu et al ., 1985; Mortelmans et al ., 1986, RL not specified) . Urea caused DNA single 

strand breaks in mammalian cells in mouse lymphoma cells (Garberg et al ., 1988, RL not specified) 

but not rat hepatocytes (Sina et al., 1984, RLnot specified) . Urea was clastogenic in a Mouse 

Lymphoma TK Locus Assay; but only at concentrations much beyond the physiological range 

(about 50-100 higher concentrations than found in human blood) (Wangenhaim. and Bolcsfoldi, 

1988, RL not specified) . The positive genotoxic findings may depend on secondary cellular effects 

(e .g . difference in osmotic pressure across the cell membrane) at high concentration which might 

not take place under in vivo conditions. The maximally effective concentration or production of 

chromosome aberrations in Chinese hamster fibroblast cells was 266 mmolar, a very high 

concentration suggesting a low clastogenic potential (Ishidate and Odashima, 1977, RL not 

specified) . Chromosomal aberrations were detected in 20% of metaphases of Chinese hamster 

fibroblast cells at urea concentration of 13 g/L (216 mmolar) indicate a low clastogenic potential 

(Ishdate et al . 1981, RL not specified) . The mechanism of genotoxicity is probably non-specific 

(e.g . difference in osmotic pressure across the cell membrane). 

I1 
UREA, REACTION PRODUCTS WTTH FORMALDEHYDE 

3.1.5 Toxicity for Reproduction 

Standard reproductive toxicity studies have not been conducted with UF or urea. Urea is an 

important endogenous product of mammalian metabolism. This may partly explain why it has not 

been rigorously studied with toxicological tests. Nevertheless, urea appears to cause little or no 

toxicity to most manunalian species (ruminants are an exception) and humans at reasonable dose 

levels (UNEP, no date specified) . 

Effects on Fertility 

The studies cited under repeated dose toxicity for urea did not indicate any toxic effects on the 

reproductive organs of mice and rats. No NOAEL can be given for the reproductive/developmental 

toxicity of urea because appropriate studies are lacking (UNEP, no date specified) . 

Developmental Toxicity 

No adequate teratogenicity/developmental toxicity studies of urea with mammals were located. 

According to one rat study, 50 g/kg body weight/day administered by gavage in two doses 12 hours 

apart for an average of 14 days did not cause outstanding (external) teratogenicity ; the mean birth 

weight of the newborn was lower but the litter size greater. Injection of urea into the air sack of 

eggs shows that urea is toxic to the development of chick embryo (UNEP, no date specified) . 

4 HAZARDS TO THE ENVIRONMENT 

4.1 Aquatic Effects 

Acute aquatic toxicity studies were not located for UF; data on urea is expected to be representative 

of UF based on its degradation to urea, carbon dioxide and ammonia. Urea has generally low acute 

ecotoxicity to organisms. The degradation product of urea, ammonia, is known to be toxic to all 

vertebrates. In neutral and acidic conditions, however, ammonia exists in the form of ammonium. 

Instead of toxic effects, more emphasis should be put on the indirect influence of urea to the 

environment via eutrophication and the pollution risk of urea to groundwater, when urea is used as a 

fertilizer and a deicer agent in airports . Also the long-term influence of urea use e.g . soil 

acidification after the long-term fertilization and ammonia emissions to air can have influence to the 

whole ecosystem and should be considered (UNEP, no date specified) . 

Acute Toxicity Test Results 

Urea is not acutely toxic to fish, algae or aquatic invertebrates . Examples of published data include 

an LC50 for 96 hours > 9100 mg/L for Barilius barna (Dodriyal and Bahuguna, 1988, RL not 

specified) ; a toxicity threshold for 192 hours > 10000 mg/L for Scenedesmus quadricauda 

(Bringmann and Kuhn, 1978, RL not specified) and an EC50 for 24 hours > 10000 mg/L for 

Daphnia magna (Bringmann and Kuhn, 1982, RL not specified) . 

5 RECOMMENDATIONS 

Additional testing is not required for UF. The existing or modelled data for UF in combination with 

published data on urea provides a complete profile for this substance. 

12 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

6 REFERENCES 

Berry, W.T., Riggs, J.K., and Kunkel, H.O. (1956) The lack of toxicity of biuret to animals. Journal 

of Animal Sciences 15:225 . 

Bringmann, G. and Kuhn, R. (1978) Vom Wasser, 50, 45-60, (1978) as cited in OECD/SIDS. 

Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, 

(1994) 

Bringmann, G. and Kuhn, R. (1982) Zeitschrift fuer Wasser und Abwasser Forschung, 15(1), 1-6, 

(1982) as cited in OECD/SIDS. Screening Information Data Set (SIDS) of OECD High Production 

Volume Chemicals Programme, (1994) 

Chaurasia, O. P. and Sinha, S. P. (1987) Cytologia, 52, 877-882, (1987) as cited in OECD/SIDS. 

Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, 

(1994) 

Dodriyal, A. K. and Bahuguna, A. K. Himalayan (1988) Chemical Pharma. Bulletin, 5, 15-16, 

(1988) as cited in OECD/SIDS. Screening Information Data Set (SIDS) of OECD High Production 

Volume Chemicals Programme, (1994) 

The Fertilizer Institute (2007) Personal Communication with William Herz, Vice President, 

Scientific Programs, TFI, Washington, DC. 

Fleischman, R. W. et al. Journal of Environmental Pathology and Toxicology, 3(5/6), 149-170, 

(1980) as cited in OECD/SIDS Screening Information Data Set (SIDS) of OECD High Production 

Volume Chemicals Programme, (1994) 

Fonnesbeck, P.V., Kearl, L.C . and Harris, L.E . (1975) Feed Grade Biuret as a Protein Replacement 

for Ruminants. Journal of Animal Science, vol 40, no. 6, pp. 1150-1184. 

FDA (US-Food and Drug Admin.) (1978) Health Hazard Evaluation Determination Report, PB288673, (1978) as cited in OECD/SIDS Screening Information Data Set (SIDS) of OECD High 

Production Volume Chemicals Programme, (1994) 

Garberg, P. et al . (1988) Mutation Research, 203, 155-176, (1988) as cited in OECD/SIDS 

Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, 

(1994) 

Hays JT and Haden WW (1966) Soluble fraction of ureaform - nitrification, leaching and burning. J 

Ag Food Chem Vol 14 No 4 pp 339-341 . 

Ishidate, M. and Odashima, S. (1977) Mutation Research, 48, 337-354, (1977) as cited in 

OECD/SIDS Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals 

Programme, (1994) . 

Ishidate, M. et al. (1981) GANN Monograph on Cancer Research, 27, 95-108, (1981)as cited in 

OECD/SIDS Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals 

Programme, (1994). 

13 
UREA, REACTION PRODUCTS WITH FORMALDEHYDE 

Jahns, T and Kaltswasser, H (2000) Mechanism of Microbial Degradation of Slow Release 

Fertilizers, Journal of Polymers and the Environment V 8 No 1, pp 11-16. 

Kaempffe GC and Lunt OR (1967) Availability of various fractions of urea-formaldehyde. J Agr 

Food Chem V 15 No 6 pp 967-971 . 

Katz, SE and Fassbender, CA (1966) Biodegradability of Ureaformaldehydes and Related 

Compounds. J Agr and Food Chemistry V 14, No 4 pp 336-339. 

Long and Winsor (1960) as cited in Kaempffe and Lunt (1967). 

Mortelmans, K. et al . (1986) Environmental Mutagenesis, 8 Suppl. 7, 1-119, (1986) as cited in 

OECD/SIDS Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals 

Programme, (1994). 

Murray, T.P ., Austin, E.R., Howard, R.G., and Horn R.C. Anal. Chem., vol 54, 1505, 1982. 

Sato, N. et al . Oyo Yakuri (1978) (Pharmacometrics), 13, 749-772, (1978) as cited in OECD/SIDS 

Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, 

(1994). 

Shimizu, H. et al. (1985) Japanese Journal of Industrial Health, 27, 400-419, (1985) as cited in 

OECD/SIDS Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals 

Programme, (1994) . 

Sina, J. F. et al . (1984) Mutation Research, 113, 357-391, (1984) as cited in OECD/SIDS Screening 

Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, (1994). 

USEPA (no date specified) AP 42, Fifth Edition, Volume I Chapter 8: Inorganic Chemical Industry 

http ://www epa gov/ttn/chief/ap42/ch08/final/c08s02 .ndf. 

UNEP Publications (date not specifed) OECD SIDS, Urea. 

Wangenhaim, J. and Bolcsfoldi, G. Mutagenesis, 3, 193-205, (1988) as cited in OECD/SIDS 

Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, 

(1994) . 
IU CLID 

Data Set 

Existing Chemical : ID: 68611-643 

CAS No. : 68611-64-3 

EINECS Name : Urea, reaction products with formaldehyde 

EC No. : 271-898-1 

Producer related part 

Company : Epona Associates, LLC 

Creation date : 28.06.2007 

Substance related part , 

Company : Epona Associates, LLC 

Creation date : 28.06.2007 

Status . 

Memo : TFI 

Printing date : 29.02.2008 

Revision date . 

Date of last update : 29.02.2008 

Number of pages : 32 

Chapter (profile) : Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10 

Reliability (profile) : Reliability: without reliability, 1, 2, 3, 4 Flags (profile) : Flags: without flag, confidential, non confidential, WGK (DE), TA-Luft (DE), Material Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDS 
p. 1 

1 . General Information 

1 .0 .1 APPLICANT AND COMPANY INFORMATION 

1 .0 .2 LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR 

1 .0 .3 IDENTITY OF RECIPIENTS 

1 .0 .4 DETAILS ON CATEGORY/TEM PLATE 

Id 68611-64-3 

Date 29.02.2008 

Comment : Urea, reaction products with formaldehyde is represented by methylene 

diurea 

Remark 

28.06.2007 

In summary, although this is a complex and variable mixture, 

enough is known about its chemistry and overall composition 

to derive a well-informed hazard characterization based on 

adequate studies of components and degradation products. 

MDU is the primary component of CAS No 68611-64-3 and was 

selected, using scientific rationale, as the most 

representative material with sufficient data that would be 

an adequate surrogate to represent this variable mixture. 

Slow-release, or ureaform, fertilizers are produced from the 

reaction of urea, formaldehyde, sodium hydroxide and water. 

Ureaform reaction is initiated by the addition of acid, 

forming a wide distribution of methyleneurea polymers, the 

lowest member of the polymers is methylenediurea (MDU; CAS 

No 13547-17-6). MDU, the smallest member of the 

methyleneurea polymers series, is used as a structural 

analogue to represent the population of larger polymeric 

methyleneurea polymers as described by CAS No 68611-64-3 . 

In addition, MDU is the largest component of the 

methyleneurea polymers found in ureaform fertlizers . 

Comment : Urea, reaction products with formaldehyde is represented by methylene 

diurea 

Remark : MDU is the principle compound formed when the formaldehyde 

additive reacts with hot urea . 

10.07.2007 (13) (19) 

Comment : Urea, reaction products with formaldehyde is represented by methylene 

diurea 

Remark 

29.02.2008 

Isopropyl methylenediurea (CAS No. 6104-30-9; chemical name 1,1'-(2-

methylpropane-1,1-diyl)diurea) is considered to-b~ :an3a~log_of MDU. The 

only difference between them is the substitutioiiofi isop~~opjrl for H on the 

methylene carbon . 

1 .1 .0 SUBSTANCE IDENTIFICATION 

IUPAC Name . Urea, reaction products with formaldehyde 

Smiles Code . 

Molecular formula . Unknown, Variable, Complex, Biological 

2/32 
p. 16 

1 . General Information 

Molecular weight 

Petrol class 

Id 68611-64-3 

Date 29.02.2008 

Remark : Urea, reaction products with formaldehyde (CAS NO 

68611-64-3) is an indeterminate mixture of variable 

composition derived as a byproduct from a chemical process . 

To understand how this material relates to other chemicals 

that have relevant data and to appreciate the potential 

range of various components, it is useful to comprehend the 

process and process variables that contribute to the 

production of this byproduct mixture. 

28.06.2007 

1.1 .1 GENERAL SUBSTANCE INFORMATION 

Purity type : typical for marketed substance 

Substance type . 

Physical status . 

Purity . 

Colour . 

Odour . 

Remark : CAS 68611-64-3 is not manufactured or processed for 

28.06.2007 

distribution in commerce as chemical substances per se and, 

relative to the fertilizer industry, have no commercial 

purpose separate from the substance mixture or article of 

which they may be a part (40 CFR § 710.4(d). 

Fertilizer grade ureaform is composed primarily of a mixture 

of straight chain polymers of urea and formadlehyde 

containing as many as 6 urea residues . 

Slow-release, or ureaform, fertilizers are produced from the 

reaction of urea, formaldehyde, sodium hydroxide and water. 

Ureaform reaction is initiated by the addition of acid, 

forming a wide distribution of methyleneurea polymers, the 

lowest member is methylenediurea . The final product contains 

unreacted urea, methylenediurea, methylenetriurea and longer 

chain polymers. 

Purity type : typical for marketed substance 

Substance type . 

Physical status . 

Purity . 

Colour . 

Odour . 

Remark : Fertilizer grade ureaform is composed primarily of a mixture 

28.06.2007 

1 .1 .2 SPECTRA 

of straight chain polymers of urea and formaldehyde 

containing as many as 6 urea residues . 

1 .2 SYNONYMS AND TRADENAMES 

(7) (14) 

(3) (9) 

3/32 
p. 17 

1 . General Information 

1 .3 IMPURITIES 

1 .4 ADDITIVES 

1.5 TOTAL QUANTITY 

Quantity 

Remark 

09.07.2007 

1 .6.1 LABELLING 

1 .6 .2 CLASSIFICATION 

1 .6.3 PACKAGING 

1.7 USE PATTERN 

0 - tonnes in 2005 

Id 68611-643 

Date 29.02.2008 

Urea, reaction products with formaldehyde, as represented by 

MDU, is considered an impurity of urea with no commercial 

purpose for reporting under TSCA Section 8 Inventory Update 

Reporting (IUR), is not manufactured or processed for 

distribution in commerce as a chemical substances per se 

and, relative to the fertilizer industry, has no commercial 

purpose separate from the substance mixture or article of 

which they may be a part (40 CFR § 710.4(d). MDU is not a 

commercial product; it is produced incidentally during the 

production of urea fertilizers and as such is not reportable 

under the Inventory reporting Rule. The members of The 

Fertilizer Institute are not Tier 1 producers of MDU 

Type of use ; use 

Category 

Remark : Urea Reaction r d t M, f 

10.07.2007 

, p o uc s wi ormaldehyde, as represented by MDU is produced incidentally in the production of urea 

fertilizers ; it is not produced commercially by the members of The Fertilizer Institute. 

Type of use : use 

Category 

Remark On April 15, 2002, the Environmental Protection Agency (EPA) issued its tolerance reassessment decision for the frost 

protectant pesticide urea, and is inviting public comment 

until May 15, 2002. EPA finds that urea poses no risk 

concerns within the limits of the existing tolerance 

exemptions . Therefore, no additional risk mitigation is 

needed, and no changes will be made to the 78 urea tolerance 

exemptions as a result of this reassessment decision . EPA regards the 78 exemptions as completed tolerance 

(15) 

(15) 

4/32 
p. 18 

1 . General Information Id 68611-643 

Date 29.02.2008 

reassessments, contributing toward the Agency's goal of 

completing 66% of all required tolerance reassessment 

decisions by August 3, 2002. 

A naturally occurring compound in humans, urea is approved 

for several human therapeutic uses. In addition, urea is 

considered "Generally Recognized As Safe" (GRAS) as affirmed 

by the U. S. Food and Drug Administration for use in food. 

Urea is an active ingredient in only one registered 

pesticide product, Enfrost, which is registered for 

commercial application to a wide variety of field crops, 

vegetables, fruit trees, and ornamentals to reduce frost 

formation by ice-nucleating bacteria naturally present on 

leaf surfaces. Urea also is an inert ingredient included in 

pesticide products as a stabilizer, inhibitor, or 

intensifier. Outside the pesticide realm, urea is included 

in fertilizer, used as an animal feed supplement, and used 

in the manufacture of dyes, fire retardant paints, 

plasticizers, and stabilizers for explosives . 

The Federal Register notice is available on EPA's website at 

http ://www .epa .gov/fedrgstr. Risk assessments and related 

documents for urea also are available at 

http ://www .epa .gov/oppsrrd 1 /reregistration/urea/. 

Test substance : Urea 

09.07 .2007 (17) 

Type of use : use 

Category . 

Remark : 21 C.F .R . § 184.1923 Urea. 

Title 21 - Food and Drugs 

Title 21 : Food and Drugs 

PART 184-DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY 

RECOGNIZED AS SAFE 

Subpart B-Listing of Specific Substances Affirmed as GRAS 

Browse Previous I Browse Next 

§ 184.1923 Urea . 

(a) Urea (CO(NH2)2, CAS Reg. No. 57-13-6) is the diamide of 

carbonic acid and is also known as carbamide. It is a white, 

odorless solid and is commonly produced from C02 by 

ammonolysis or from cyanamide by hydrolysis . (b) FDA is developing food-grade specifications for urea in 

cooperation with the National Academy of Sciences. In the 

interim, this ingredient must be of a purity suitable for 

its intended use. 

(c) In accordance with §184.1(bx1), the ingredient is used 

in food with no limitation other than current good 

manufacturing practice . The affirmation of this ingredient 

as generally recognized as safe as a direct human food 

ingredient is based upon the following current good 

manufacturing practice conditions of use: 

(1) The ingredient is used as a formulation aid as defined 

in §170.3(o)(14) of this chapter and as a fermentation aid. 

(2) The ingredient is used in yeast-raised bakery products; 

in alcoholic beverages as defined in §170.3(n)(2) of this 

chapter; and in gelatin products. 

(d) Prior sanctions for this ingredient different from the 

uses established in this section do not exist or have been 

waived. 

[48 FR 51616, Nov. 10, 1983, as amended at 49 FR 19816, May 

10,1984] 

Test substance : Urea 

5/32 
p. 19 

1 . General Information Id 68611-643 

Date 29.02 .2008 

09.07.2007 (16) 

Type of use : use 

Category . 

Remark : Urea is approved for several therapeutic uses in humans with 

relatively few toxicities . Urea is used primarily as an 

osmotic agent for inducing diuresis and reducing 

intraoccular and intracranial pressure. Urea has also been 

used as a topical anesthetic for the treatment of mouth and 

throat inflammation (10-15% urea gel, liquid or solution), 

to debride necrotic and infected tissues, i .e. fingernails 

and toenails . It is also used in the treatment of sicklecell anemia and to ammoniate dentrifices as well as a basic 

ingredient in the synthesis of medically important compounds 

such as barbiturates and urethanes. 

http ://www .epa .gov/oppsrrd1/REDs/urea tred .htm ; 

http ://216 .239 .51 .104/search?q=cache:p-1264Z8FFIJ:www.fda .go 

vcder/ogd/rld/12154s24 .pdf+FDA+category+C+urea&hl=en&ct=clnk 

&d=1 &gl=us 

Test substance : Urea 

09.07.2007 

1 .7.'1 DfTAfLED -USE PATTERN 

1.7.2 METHODS OF MANUFACTURE 

Origin of substance : Polymer 

Type : Production 

Remark Slow-release, or ureaform, fertilizers are produced from the 

reaction of urea, formaldehyde, sodium hydroxide and water. 

Ureaform reaction is initiated by the addition of acid, 

forming a wide distribution of methyleneurea polymers, the 

lowest member of the polymers is methylenediurea (MDU; CAS 

No 13547-17-6). MDU, the smallest member of the 

methyleneurea polymers series, is used as a structural anlog 

to represent the population of larger polymeric 

methyleneurea polymers as described by CAS No 68611-64-3 . 

In addition, MDU is the largest component of the 

methyleneurea polymers found in ureaform fertlizers. 

Urea reaction products are formed when formaldehyde-based 

additives (FBA) are added to the hot urea (apx. 280o F) 

process at low concentration . FBA immediately and 

essentially irreversibly reacts to form methyleneureas, at 

which point the formaldehyde loses its chemical identity. 

The principal reaction product in the resulting urea product 

is methylenediurea (MDU). 

In the presence of strong acids, the reaction does not stop 

at MDU, but rather forms methyleneurea polymers. 

Methyleneureas are condensation products of urea and 

formaldehyde of different molecular mass and solubility; 

they are used in large amounts both as resins, binders, and 

insulating materials for industrial applications, as well as 

a slow-release nitrogen fertilizer for greens, lawns, or in 

bioremediation processes. While this discussion will focus 

primarily on MDU, additional data are presented for other 

methyleneurea polymers . 

(18) 

6/32 
p. 20 

1 . General Information Id 68611-64-3 

Date 29.02.2008 

Urea, reaction products with formaldehyde (CAS NO 

68611-64-3) is an indeterminate mixture of variable 

composition derived as a byproduct from a chemical process . 

To understand how this material relates to other chemicals 

that have relevant data and to appreciate the potential 

range of various components, it is useful to comprehend the 

process and process variables that contribute to the 

production of this byproduct mixture. 

28.06.2007 

1 .8 REGULATORY MEASURES 

Remark Fertilizers, fertilizer materials, and their manufacturing 

facilities are highly regulated at the federal and state 

level . At the federal level, standards are in place to 

govem: (I) air emissions from fertilizer and 

fertilizer material manufacturing facilities [These 

regulations are found at : (1) 40 C.F.R. Part 60, Subpart G 

(standards of performance for nitric acid 

plants); (2) 40 C.F .R . Part 60, Subpart H (standards of 

performance for sulfuric acid plants); (3) 40 C.F .R. Part 

60, Subpart T (standards of performance for wet process 

phosphoric acid plants); (4) 40 C.F .R. Part 60, Subpart U 

(standards of performance for superphosphoric acid plants); 

(5) 40 C.F .R. Part 60, Subpart V (standards of 

performance for diammonium phosphate plants); (6) 40 C.F .R . 

Part 60, Subpart W (standards of performance for 

triple superphosphate plants); (7) 40 C.F .R . Part 60, 

Subpart X (standards of performance for granular triple 

supetphosphate storage facilities) ; (8) 40 C.F .R . Part 60, 

Subpart NN (standards of performance for phosphate rock 

plants); (9) 40 C.F .R. Part 60, Subpart PP (standards of 

performance for ammonium sulfate plants); (10) 40 C.F .R. 

Part 61, Subpart R (national emission standards for radon 

emissions ftom phosphogypsum stacks); (11) 40 C.F .R.] ; (2) 

solid and hazardous waste generation, storage, 

transportation, and disposal [40 C.F .R. §§ 260-299.] ; (3) 

water discharges [40 C.F .R . Part 122.]; (4) accident 

prevention and mitijation [40 C.F .R . Part 68 and 29 C.F .R. § 

1910.119.] ; (5) release reporting [40 C.F .R. §§ 302 .4, 

355.40 and 40 C.F .R. Part 372. ] ; (6) worker exposure [29 

C.F .R . §§ 1910.1000 and 1910.1020.] ; (7) hazard 

communication [29 C.F.R. § 1910.1200]; and 

(8) transportation [49 C.F.R.SubchapterC] . These 

regulations provide a comprehensive federal program to 

regulate fertilizers and fertilizer materials . In addition, 

and without conceding any arguments that could 

be made to the contrary, TSCA § 6 provides EPA with the 

authority to either prohibit or limit the manufacture of a 

chemical substance upon a finding that its manufacture, 

processing, distribution in commerce, use, or disposal 

"presents or will present an unreasonable risk of injury to 

health or the environment." Also, under TSCA § 7, the Agency 

has the authority to take certain actions in 

response to an "imminently hazardous chemical substance or 

mixture." In addition to federal regulations, the states 

regulate fertilizers and fertilizer materials. As noted 

in the attached document, entitled Summary of State 

Fertilizer Laws, 48 states have laws and 

7/32 
p. 21 

1 . General Information 

09.07.2007 

Id 68611-643 

Date 29.02.2008 

regulations in place to regulate fertilizers and fertilizers 

materials . Many of these states have an 

"adulteration" clause in their laws that enable the 

responsible state agency to stop the sale of 

fertilizers and fertilizer materials that are dangerous to 

human health . Notably, five states have adopted 

comprehensive regulations to limit the amounts of 

nonnutritive elements in fertilizers . These states are 

Washington, California, Oregon, Florida and 

Texas. EPA, in response to a congressional inquiry, endorsed 

these programs. Other states are developing similar 

regulations fostered by the work of the Association 

of American Plant Food Control Officials (AAPFCO). 

1.8 .1 OCCUPATIONAL EXPOSURE LIMIT VALUES 

1 .8 .2 ACCEPTABLE RESIDUES LEVELS 

1 .8.3 WATER POLLUTION 

1.8.4 ACCH)ENT ' HAZARDS 

1 .8 .5 AIR POLLUTION 

1 .8.6 LISTINGS E.G. CHEMICAL INVENTORIES 

1 .9.1 DEGRADATION/TRANSFORMATION PRODUCTS 

1 .9.2 COMPONENTS 

1 .10 SOURCE OF EXPOSURE 

1 .11 ADDITIONAL REMARKS 

1 .12 LAST LITERATURE SEARCH 

1 .13 REVIEWS 

8/32 
p. 22 

2. Physico-Chemical Data 

2.1 MELTING POINT 

Value . 212 - 214 °C 

Sublimation . 

Method : other: melting point block 

Year : 1966 

GLP : no 

Test substance : other TS: MDU 

Id 68611-64-3 

Date 29.02.2008 

Method : The crude product was slurried with methanol, cooled to 40 C 

and filtered warm. The filtrate was held at OC for 16 hours 

and the crytalline product filtered off (MP = 213C). Because 

of the heat sensitivity of MDU and Dimethyleneurea (DMU) the 

sample had to be droppped on a melting point block heated to 

within about 5C of the final melting point to get complete 

melting. The melting points quoted were taken in this 

manner. The extraction procedure was rpeated until the 

melting point began to increase. In this way, 70% of crude 

product was isolated as sharp melting crystals (212-214 C). 

Reliability : (2) valid with restrictions 

Published information 

28.06.2007 

2.2 BOILING POINT 

Decomposition 

Method 

Year 

GLP 

Test substance 

2007 

no 

as prescribed by 1 .1 - 1 .4 

Remark : The substance is a solid; BP is not appropriate 

Reliability : (2) valid with restrictions 

Technical discussion regarding physical properties 

28.06.2007 

2.3 DENSITY 

2.3.1 GRANULOMETRY 

2A VAPOUR PRESSURE 

Decomposition 

Method 

Year 

GLP 

Test substance 

Remark 

Reliability 

28.06.2007 

2007 

no 

as prescribed by 1 .1 - 1 .4 

The substance is a solid ; VP is not appropriate 

(2) valid with restrictions 

Technical discussion regarding physical properties 

(5) 

9/32 
p. 23 

2. Physico-Chemical Data 

2.5 PARTITION COEFFICIENT 

Partition coefficient : octanol-water 

Log pow . -3 .01 at °C 

pH value . 

Method : other (calculated) 

Year : 2007 

GLP : no 

Test substance : other TS: MDU 

Method : KOWWIN Program (v1 .67) : 

------------------------------- ------------------------------- 

SMILES : 0=C(NCNC(=0)N)N 

CHEM : Urea, N,N"-methylenebisMOL FOR: C3 H8 N4 02 

MOL WT : 132.12 

Id 68611-64-3 

Date 29.02.2008 

Physical Property Inputs: 

Water Solubility (mg/L): 25000 

Vapor Pressure (mm Hg) : ------

Henry LC (atm-m3/mole) : -----

Log Kow (octanol-water): ------

Boiling Point (deg C) : ------

Melting Point (deg C) : 212.00 

Remark : CAS 68611-64-3 is UCVB ; modeling is not appropriate 

Result : KOWWIN Program (v1 .67) Results : 

------------------------------- ------------------------------- 

Log Kow(version 1 .67 estimate) : -3.01 

----+---------+------- 

TYPE I NUM I LOGKOW FRAGMENT DESCRIPTION 

COEFF I VALUE 

-------+-----+---------------------------------------+-

-------+------- 

Frag ~ 1 1 -CH2- [aliphatic carbon] 

0.4911 1 0.4911 

Frag ~ 2 1 -NH2 [aliphatic attach] 

1-1 .4148 1-2.8296 

Frag 1 2 1 -NH- [aliphatic attach] 

1-1 .4962 1-2 .9924 

Frag 1 2 1 -NC(=0)N- [urea] 

1 .0453 ~ 2.0906 

Const ~ I Equation Constant 

1 0.2290 

-------+-----+----------------------------------------+-

-------+-------- 

Log 

Kow = -3 .0113 

Reliability : (2) valid with restrictions 

Modeled data 

28.06.2007 (4) 

2.6 .1 SOLUBILITY IN DIFFERENT MEDIA 

Solubility in : Water 

Value . 25 g/I at 25 °C 

pH value . 

10/32 
p. 24 

2. Physico-Chemical Data 

concentration . at °C 

Temperature effects . 

Examine different pol . . 

pKa : at 25 °C 

Description . 

Stable . 

Deg. product . 

Method : other 

Year : 1966 

GLP : no 

Test substance : other TS : MDU 

Id 68611-64-3 

Date 29.02.2008 

Remark : The water solubility of dimethylenetriurea at 25C was 1 g/L . 

Result : 70 g/L at 50C 

Reliability : (2) valid with restrictions 

Published information 

28.06 .2007 

2.6 .2 SURFACE TENSION 

2.7 FLASH POINT 

2.8 AUTO FLAMMABILITY 

2.9 FLAMMABILITY 

2.10 EXPLOSIVE PROPERTIES 

2.11 OXIDIZING PROPERTIES 

2.12 DISSOCIATION CONSTANT 

2.13 VISCOSITY 

2.14 ADDITIONAL REMARKS 

(5) 

11/32 
p. 25 

3. Environmental Fate and Pathways 

3.1 .1 PHOTODEGRADATION 

Type 

Light source 

Light spectrum 

Relative intensity 

INDIRECT PHOTOLYSIS 

Sensitizer 

Conc. of sensitizer 

Rate constant 

Degradation 

Deg. product 

Method 

Year 

GLP 

Test substance 

Method 

Remark 

Result 

. air 

: Sun light 

. nm 

. based on intensity of sunlight 

: OH 

: 5000 molecule/cm' 

. .00000000000197 cm'/(molecule*sec) 

. 50 % after .5 day(s) 

other (calculated) 

2007 

no 

other TS : MDU 

Id 68611-64-3 

Date 29.02.2008 

AOP Program (v1 .92) 

SMILES : 0=C(NCNC(=0)N)N 

CHEM : Urea, N,N"-methylenebisMOL FOR: C3 H8 N4 02 

MOL WT : 132.12 

CAS 68611-64-3 is UCVB; modeling is not appropriate 

AOP Program (v1 .92) Results: 

--------------------------- ---------------------------

--- SUMMARY (AOP v1 .92): HYDROXYL RADICALS 

Hydrogen Abstraction = 15.7005 E-12 cm3/molecule-sec 

**Reaction with N, S and -OH = 4.0000 E-12 

cm3/molecule-sec 

Addition to Triple Bonds = 0.0000 E-12 cm3/molecule-sec 

Addition to Olefinic Bonds= 0.0000 E-12 cm3/molecule-sec 

Addition to Aromatic Rings= 0.0000 E-12 cm3/molecule-sec 

Addition to Fused Rings = 0.0000 E-12 cm3/molecule-sec 

OVERALL OH Rate Constant = 19.7005 E-12 cm3/molecule-sec 

HALF-LIFE= 0.543 Days (12-hr day; 1 .5E6 OH/cm3) 

HALF-LIFE = 6.515 Hrs 

. . . . . . . . . . . . . . . . . . . . . . . . ** Designates Estimation(s) Using 

ASSUMED Value(s) 

------------------ SUMMARY (AOP v1 .91) : OZONE REACTION 

****** NO OZONE REACTION ESTIMATION ****** 

(ONLY Olefins and Acetylenes are Estimated) 

Reliability 

28.06.2007 

Experimental Database: NO Structure Matches 

Fraction sorbed to airborne particulates (phi): 0.00474 

(Junge,Mackay) 

Note: the sorbed fraction may be resistant to 

atmospheric oxidation 

: (2) valid with restrictions 

Modeled data 

(4) 

12/32 
p. 26 

3. Environmental Fate and Pathways 

3.1 .2 STABILITY IN WATER 

Type : abiotic 

t1/2 pH4 . at °C 

t1/2 pH7 . at °C 

t1/2 pH9 . at °C 

Degradation . 50 % after 1 year at pH and °C 

Deg. product . 

Method : other (calculated) 

Year : 2007 

GLP : no 

Test substance : other TS: MDU 

Method 

Remark 

Result 

Id 68611-64-3 

Date 29.02.2008 

HYDROWIN Program (v1 .67) 

SMILES : 0=C(NCNC(=0)N)N 

CHEM : Urea, N,N"-methylenebisMOL FOR: C3 H8 N4 02 

MOL WT : 132.12 

Physical Property Inputs: 

Water Solubility (mg/L): 25000 

Vapor Pressure (mm Hg) : ------

Henry LC (atm-m3/mole) : ------

Log Kow (octanol-water): ------

Boiling Point (deg C) : ------

Melting Point (deg C) : 212 .00 

CAS 68611-64-3 is UCVB; modeling is not appropriate 

HYDROWIN Program (v1 .67) Results: 

-------------------------------- --------------------------------

------- HYD ROW I N v1 .67 Results ------------------------- 

UREA: -N-C(=0)-NCompound has a urea group; C=0 located at SMILES atom #: 2 

Hydrolysis Rate Extremely Slow or t1/2 > 1 Year 

***** CALCULATION NOT PERFORMED ***** 

UREA: -N-C(=0)-NCompound has a urea group; C=0 located at SMILES atom #: 6 

Hydrolysis Rate Extremely Slow or t1/2 > 1 Year 

***** CALCULATION NOT PERFORMED 

Reliability : (2) valid with restrictions 

Modeled data 

***** 

09.07.2007 (4) 

3.1 .3 STABILITY IN SOIL 

Type : laboratory 

Radiolabel : no 

Concentration . 

Soil temperature . °C 

Soil humidity . 

Soil classification . 

Year . 

Deg. product . 

Method : other 

Year : 1966 

GLP : no 

13/32 
p. 27 

3. Environmental Fate and Pathways 

Test substance : other TS: MDU, DDU 

Id 68611-64-3 

Date 29.02 .2008 

Method : Procedure described in Clark, KG, Yee, JT, Lundstrom, FO, 

Lamont, TG. (1959) J Assoc Offic Agr Chemists 42, 596and in 

Hays JT, Haden, WW and Anderson, LE (1965) J Agr Food 

Chemists, 13, 176. 

Result : Negligible nitrification occurred in the first eight days on 

reference soil . Urea reached 80% conversion to nitrate 

after 12 days, MDU nitrification was slower (about 30% in 12 

days; 90% in 14 days) and dimethylene dinitriurea (DDU) 

nitrification was slower still (about 15% in 12 days; 50% in 

14 days). 

In a second experiment, water was added to the soil 10 days 

before the addition of the test substances to allow the 

build-up of nitrifying bacteria . The induction period was 

nearly eliminated for urea (100% in 8 days), while MDU and 

DDU required 8 or 9 days to begin production of significant 

amounts (after 16 days about 90% for MDU and about 30% for 

DDU) of nitrate. 

Conclusion : The rates of nitrification of the methyleneureas are clearly 

slower than urea; there appears to be about a week delay 

before nitrification of the nonurea, soluble ureaform 

components begin, and the subsequent rate is dependent on 

molecular weight. 

Reliability : (2) valid with restrictions 

Published information 

10 .07.2007 

Type : laboratory 

Radiolabel . 

Concentration . 

Soil temperature . °C 

Soil humidity . 

Soil classification . 

Year . 

Deg . product . 

Method : other 

Year : 1960 

GLP : no 

Test substance : other TS: MDU and DDU 

(5) 

Result : 85% nitrification of MDU and DDU was observed in three 

weeks; 68% of trimethylene tetraurea and <5% tetramethylene 

pentaurea was observed in the same period . 

Reliability : (4) not assignable 

Original article not reviewed 

10.07.2007 (9) (11) 

Type : laboratory 

Radiolabel . 

Concentration . 

Soil temperature . °C 

Soil humidity . 

Soil classification . 

Year . 

Deg. product . 

Method : other 

Year : 1967 

GLP : no 

Test substance : other TS: MDU, other polymers 

14/32 
p. 28 

3. Environmental Fate and Pathways Id 68611-64-3 

Date 29.02.2008 

Method : To determine if the soluble forms in ureaforms are directly 

available to the plant, grass was grown and established . 

Nutrient solutions in which No3, urea, MDU, dimethylene 

triurea or trimethylene tetraurea were used as sole sources 

of nitrogen (5, 10, 25, 50 and 100 mM concentrations of 

nitrogen) in an otherwise nitrogen free solution . Growth 

responses were measured. 

Result : A delay of one week or more was required for response by 

methylene ureas. Then a rapid oincrease of growth took 

place, followed by the development of toxic effects and in 

severe cases, death. 

Reliability 

10 .07.2007 

3.2 .1 MONITORING DATA 

3.2.2 FIELD STUDIES 

The response suggests no direct utilization by the plant of 

the ureaforms or methylenureas as there was a substantial 

time delay in achieving a normal growth rate . Breakdown of 

the condensates by internal cleavage of methylene linkages 

and release of free urea, or exposure and cleavage of 

internal amino groups resulting in NH4 absorption are 

suggested mechanisms for utilization of these materials by 

plants . Solution anlaysis indicates that the observed 

toxicity effects were probably due to cleavage to urea 

molecules and subsequent hydrolysis to ammonia. The 

relatively high levels of ammonia at the pH levels (pH 4.5 

to 5.5) produced the toxicity. 

(2) valid with restrictions 

Published information 

3.3.1 TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS 

Type : other: leaching 

Media : water - soil 

Air . % (Fugacity Model Level I) 

Water . % (Fugacity Model Level I) 

Soil . % (Fugacity Model Level I) 

Biota . % (Fugacity Model Level II/III) 

Soil . % (Fugacity Model Level II/III) 

Method : other 

Year : 1966 

Method : Procedure 1 : 

A soil fertilizer mixture was added to a column filled with 

wetted soil . An aspirator was used to draw filtrate through 

the column, and total nitrigen determined. 

Procedure 2: Followed the same procedure as 1 above, except 

the soil was wetted after addition of the fertilizer. 

Result : Procedure 1 : About 90% of the applied ureaform was retained 

in soil ; about 10% of the applied urea was retained in soil . 

With the more drastic leaching procedure (procedure 2) the 

retention of ureaform nitrogen was reduced to 76%, due to 

low solubility. 

Conclusion : Ureaforms such as MDU and DDU have decreased rates of 

nitrification and leaching compared to urea. 

(9) 

15/32 
p. 29 

3. Environmental Fate and Pathways 

Reliability : (2) valid with restrictions 

Published information 

10.07.2007 

Type 

Media 

Air 

Water 

Soil 

Biota 

Soil 

Method 

Year 

Method 

Remark 

Result 

fugacity model level III 

% (Fugacity Model Level I) 

% (Fugacity Model Level I) 

% (Fugacity Model Level I) 

% (Fugacity Model Level II/III) 

% (Fugacity Model Level II/III) 

other 

2007 

Id 68611-64-3 

Date 29.02.2008 

Level III Fugacity Model (Full-Output): 

--------------------------------------- --------------------------------------- 

Chem Name : Urea, N,N"-methylenebisMolecular Wt: 132.12 

Henry's LC : 1 .74e-018 atm-m3/mole (Henrywin program) 

Vapor Press : 2.82e-006 mm Hg (Mpbpwin program) 

Liquid VP : 0.000199 mm Hg (super-cooled) 

Melting Pt : 212 deg C (user-entered) 

Log Kow :-3.01 (Kowwin program) 

Soil Koc : 0.000401 (calc by model) 

CAS 68611-64-3 is UCVB ; modeling is not appropriate 

Level III Fugacity Model (Full-Output): 

--------------------------------------- --------------------------------------- 

Mass Amount Half-Life Emissions 

(percent) (hr) (kg/hr) 

Air 4.12e-011 13 1000 

Water 39 360 1000 

Soil 60.9 720 1000 

Sediment 0.0713 3.24e+003 0 

Fugacity Reaction Advection Reaction 

Advection 

(atm) (kg/hr) (kg/hr) (percent) 

(percent) 

Air 1 .32e-021 3.8e-008 7.15e-009 1 .27e-009 

2.38e-010 

Water 4.46e-023 1 .3e+003 677 43.5 

22.6 

Soil 2.58e-021 1 .02e+003 0 33.9 

0 

Sediment 4.08e-023 0.265 0.0248 0 .00883 

0.000826 

Persistence Time: 579 hr 

Reaction Time: 748 hr 

Advection Time: 2.56e+003 hr 

Percent Reacted: 77 .4 

Percent Advected: 22.6 

Half-Lives (hr), (based upon Biowin (Ultimate) and 

Aopwin): 

Air: 13.03 

Water: 360 

Soil : 720 

Sediment: 3240 

Biowin estimate: 2.907 (weeks ) 

(5) 

16/32 
p. 30 

3. Environmental Fate and Pathways Id 68611-64-3 

Date 29.02.2008 

Advection Times (hr) : 

Air: 100 

Water: 1000 

Sediment: 5e+004 

Reliability : (2) valid with restrictions 

Modeled data 

28.06.2007 (4) 

3.3.2 DISTRIBUTION 

3.4 MODE OF DEGRADATION IN ACTUAL USE 

3.5 BIODEGRADATION 

Type : aerobic 

trt6eaulum : activated sludge 

Concentration : 100 mg/I related to Test substance 

related to 

Contact time . 

Degradation . = 78 -100 (t) 0/6 after 1 month 

Result : readily biodegradable 

Deg; product . 

Method : OECD Guide-line 301 C "Ready Biodegradability: Modified MITI Test (I)" 

Year : 2002 

GLP : no data 

Test substance : other TS 

Method : Modified MITI test for biodegradation: 

Test equipment : standard type 

Test period : 4 weeks 

Chemical concentration: 100 mg/L 

Concentration "of activated sludge: 30 mg/L 

Result : Indireo Analysis: 

BOD(tVH3) = 78°l0 

Direct Analysis : 

TOC = 90% 

HPLC =100%a 

Test substance : 1,1'-(2-methylpropane-1,1-diyl)diurea ('CAS No. 61{)4=30-9; twllTI No. 2-

1742) (also known as 1,1-DiurbidoFsobutar;+s) :'This chemical is considered 

to be a valid analog for MDU. From the N `radation perspective, it is 

similar but in theory might, be slowrsr to degratf6°gisren its substitution (of 

isopr~yl ; fc~~ ~1) on the methylene carbon. 

Reliabllity : (Z) valid with restrictions' 

MITI Database is known to be a reliable source. 

29;01242-008 (12) 

Type : aerobic 

Inoculum : other: domestic sewage sludge, adapted seed cultures 

Concentration : 500 mg/I related to Test substance 

related to 

Contact time : 7 day(s) 

Degradation . (t) % after 

Result . 

Deg. product . 

Method : other: modifed Warburg 

Year : 1966 

17/32 
p. 31 

3. Environmental Fate and Pathways 

GLP : no 

Test substance : other TS: MDU's 

Id 68611-64-3 

Date 29.02.2008 

Method : Based upon the principles of the BOD test; nitrogen content 

was made the limiting factor in the test media 

Result : Methylenediurea : ca. 80% degradation in 8 days, ca. 90% 

degradation in 14 days. Dimethylenediurea: ca. 70 % 

degradation in 8 and 14 days. Trimethylenetetraurea : 40% 

degradation in 8 days, ca. 60% degradation in 14 days. 

Low MW fraction degraded 100% in 11 days 

Intermediate MW fraction degraded 70% in 11 or after 14 days 

High MW fraction degraded <10% in 11 days and ca. 10% after 

14 days 

Combined MW fractions degraded ca. 66% after 14 days 

Test substance : Methylenediurea, Dimethylentriurea, Trimethylenetetraurea . 

Also, the low, intermediate, high and total combined 

molecular weight fractions of ureaform were tested . 

Conclusion : Increases in chain length decrease biodegradability 

Reliability : (2) valid with restrictions 

Provides basic data ; uses standard method 

29.02.2008 (10) 

Type : aerobic 

Inoculum : other: Ralstonia paulcula (garden soil) 

Contact time . 

Degradation . (t) % after 

Result : readily biodegradable 

Deg. product : yes 

Method . 

Year : 2000 

GLP : no data 

Test substance : other TS:MDU and other UF polymers 

Deg. products . 

124-38-9 204-696-9 carbon dioxide 

57-13-6 200-315-5 urea 

Method : Microbial degradation of 7.5mM MDU as the sole source of 

fixed nitrogen was followed at 26C. 

Result : Nitrogen was enzymatically released from the degradation of 

methlyenediurea as ammonia and urea, and the formaldehyde 

released immediately oxidized via formiate to carbon 

dioxide. The enzyme is methylenediurease . 100% of the MDUwas 

degraded by 4 days. 

Methylenediurea may also be degraded by fungus via the 

formation of organic acids, thus leading to nonenzymatic 

degradation of methyleneureas, which are unstable under 

acidic conditions. 100% MDU was degraded at 3 days in the 

presence of Penicillium notatum. 

Reliability : (2) valid with restrictions 

Published information 

29.02.2008 

Contact time . 

Degradation . - (t) % after 

Result : other: likely to biodegrade 

Deg. product . 

Method . 

Year : 2007 

GLP : no 

Test substance : other TS: MDU 

(7) 

18/32 
3. Environmental Fate and Pathways Id 68611-64-3 

Date 29.02.2008 

Method : BIOWIN (v4.10) Program 

------------------------------ ------------------------------

SMILES : 0=C(NCNC(=0)N)N 

CHEM : Urea, N,N"-methylenebisMOL FOR: C3 H8 N4 02 

MOL WT : 132.12 

Remark : CAS 68611-64-3 is UCVB; modeling is not appropriate 

Result : BIOWIN (v4.10) Program Results: 

----------------------- BIOWIN v4.10 Results 

p. 32 

Biowin1 (Linear Model Prediction) : Biodegrades Fast 

Biowin2 (Non-Linear Model Prediction): Biodegrades Fast 

Biowin3 (Ultimate Biodegradation Timeframe) : Weeks 

Biowin4 (Primary Biodegradation Timeframe) : Days-Weeks 

Biowin5 (MITI Linear Model Prediction) : Does Not 

Biodegrade Fast 

Biowin6 (MITI Non-Linear Model Prediction): Does Not 

Biodegrade Fast 

Biowin7 (Anaerobic Model Prediction): Biodegrades Fast 

Ready Biodegradability Prediction : NO 

------+----+-----------------------------------------+--

------+-------- 

TYPE INUM I Biowin1 FRAGMENT DESCRIPTION 

COEFF I VALUE 

------+----+-------------------------------------------+-- 

------+--------

MoIWtj " I Molecular Weight Parameter 

1-0 .0629 

Constj " I Equation Constant 

1 0.7475 

RESULT I Biowin1 (Linear Biodeg Probability) 

( 0.6846 

------+-----+-----------------------------------------+--

------+-------- 

TYPE INUM I Biowin2 FRAGMENT DESCRIPTION 

COEFF I VALUE 

------+----+----------------------------------------+--

------+-------- 

MoIWtj * I Molecular Weight Parameter 

1-1 .8761 

----------__+-_---------------__------------------------- ---------- ----------------- ------------------------- 

RESULT I Biowin2 (Non-Linear Biodeg Probability) 

/ 0.7563 

A Probability Greater Than or Equal to 0.5 indicates --> 

Biodegrades Fast 

19/32 
p. 33 

3. Environmental Fate and Pathways Id 68611-64-3 

Date 29.02.2008 

A Probability Less Than 0.5 indicates --> Does NOT 

Biodegrade Fast 

------+-----+-------------------------------------+--

------+-------- 

TYPE INUM I Biowin3 FRAGMENT DESCRIPTION 

COEFF I VALUE 

------+-----+--------------------------------------------+--

------+--------- 

MoIWtj * I Molecular Weight Parameter 

1-0.2920 

Constj * I Equation Constant 

1 3.1992 

RESULT I Biowin3 (Survey Model -Ultimate Biodeg) I 

1 2.9072 

------+----+----------------------------------------+--

------+-------- 

TYPE INUM I Biowin4 FRAGMENT DESCRIPTION 

COEFF I VALUE 

------+----+----------------------------------------+--

------+-------- 

MoIWtj * I Molecular Weight Parameter 

1-0.1906 

Constj * I Equation Constant 

1 3.8477 

------------+-_----__-----------______-------__---------- ------------ ------ ----------- ------- ----------

RESULT I Biowin4 (Survey Model -Primary Biodeg) I 

1 3.6571 

------------+_________________-----------__-------------- ------------ ----------- -------------- 

Result Classification : 5.00 -> hours 4.00 -> days 

3.00 -> weeks 

(Primary & Ultimate) 2.00 -> months 1 .00 -> longer 

------+----+----------------------------------------+--

------+--------- 

TYPE INUM I Biowin5 FRAGMENT DESCRIPTION 

COEFF I VALUE 

------+-----+------------------------------------------+--

------+--------- 

Frag 1 1 1 -CH2- [linear] 

0.0494 1 0.0494 

MoIWtj * I Molecular Weight Parameter 

1-0 .3931 

Constj * I Equation Constant 

1 0.7121 

------------+-_------------------__--------___----__----- ------------ -------------------- -------- ---- -----

RESULT I Biowin5 (MITI Linear Biodeg Probability) I 

1 0.3685 

20/32 
p. 34 

3. Environmental Fate and Pathways 

Reliability 

Id 68611-64-3 

Date 29.02.2008 

------+----+-----------------------------------------+--

------+-------- 

TYPE INUM I Biowin6 FRAGMENT DESCRIPTION 

COEFF I VALUE 

-----+-----+---------------------------------------+--

------+-------- 

Frag I 1 I -CH2- [linear] 

0.4295 1 0.4295 

MoIWtj * I Molecular Weight Parameter 

1-3.8142 

RESULT jBiowin6 (MITI Non-Linear Biodeg Probability)l 

1 0 .2975 

------------ ---- 

A Probability Greater Than or Equal to 0.5 indicates --> 

Readily Degradable 

A Probability Less Than 0.5 indicates -> NOT Readily 

Degradable 

------+----+----------------------------------------+--

------+-------- 

TYPE INUM I Biowin7 FRAGMENT DESCRIPTION 

COEFF I VALUE 

------+----+----------------------------------------+--

------+-------- 

Frag 1 1 1 -CH2- [linear] 

0.0260 ~ 0.0260 

Constj * I Equation Constant 

~ 0.8361 

------------+_____________------___--------__-----__----- ------------ ------ -------- ----- ----- 

RESULT I Biowin7 (Anaerobic Linear Biodeg Prob) 

1 0 .8621 

A Probability Greater Than or Equal to 0.5 indicates --> 

Biodegrades Fast 

A Probability Less Than 0.5 indicates -> Does NOT 

Biodegrade Fast 

: (2) valid with restrictions 

Modeled data 

29.02 .2008 (4) 

3.6 13005, COD OR BOD5/COD RATIO 

21/32 
p. 35 

3. Environmental Fate and Pathways 

3.7 BIOACCUMULATION 

3.8 ADDITIONAL REMARKS 

Memo : Mineralization and nitrification 

Id 68611-64-3 

Date 29.02.2008 

Method : Three ureaform fertilizers with varying amounts of MDU and 

free urea were studied for 35 days for mineralization and 

nitrification in two soil types using 15N and HPLC 

techniques. Soils were preincubated for 1 month to allow 

microbial populations to stabilize . 

Result : Free urea and pure urea hydrolyzed completely in 7 days. 

Nitrification was complete by the end of three weeks. The 

presence of MDU or DMTU had no inhibitory or stimulatory 

effect on this hydrolysis. The mineralization of MDU 

proceeded rapidly to completion with only a 2 day lag period 

at a rate similar to that of urea. The initation of 

hydrolysis of DMTU was delayed ten days; posibly due to a 

lack of microbial populations capable of attacking this N 

product. After this lag period, the majority of the DMTU 

mineralized in 25 days. In the second soil type, DMTU 

minearlized 85% in 35 days. 

Test substance . Test % % % 

substance Urea MDU DMTU 

UF6 80.2 12.1 3.7 

UF12 60.7 20.1 7.5 

UF15 52.3 20.2 8.3 

Pure urea 100 --- --- 

Conclusion : Only triuret and DMTU components showed any slow release 

character. Since these fractions made up only a small 

percentage of each material tested the ureaforms probably 

have limited value as slow release sources. 

Reliability : (2) valid with restrictions 

Peer reviewed data; no data on GLP 

10 .07.2007 (2) 

22/32 
p. 36 

4. Ecotoxicity 

4.1 ACUTE/PROLONGED TOXICITY TO FISH 

4.2 ACUTE TOXICITY TO AQUATIC INVERTEBRATES 

4.3 TOXICITY TO AQUATIC PLANTS E.G. ALGAE 

4.4 TOXICITY TO MICROORGANISMS E.G. BACTERIA 

4.5.1 CHRONIC TOXICITY TO FISH 

4.5.2 CHRONIC TOXICITY TO AQUATIC INVERTEBRATES 

4.6.1 TOXICITY TO SEDIMENT DWELLING ORGANISMS 

4.6.2 TOXICITY TO TERRESTRIAL PLANTS 

4.6 .3 TOXICITY TO SOIL DWELLING ORGANISMS 

4.6.4 TOX. TO OTHER NON MAMM. TERR. SPECIES 

4.7 BIOLOGICAL EFFECTS MONITORING 

4.8 BIOTRANSFORMATION AND KINETICS 

Type : other 

Dog. product . 

Id 68611-64-3 

Date 29.02.2008 

Remark : The methylenediurea is hydrolysed and decarboxylated to give 

an aminated methylurea, which then spontaneously hydrolyses 

to hydroxymethylurea . The enzyme from Ochrobactrum anthropi 

also hydrolyses dimethylenetriurea and trimethylenetetraurea 

as well as ureidoglycolate, which is hydrolysed to urea and 

glyoxylate, and allantoate, which is hydrolysed to 

ureidoglycolate, ammonia and carbon dioxide. 

Reliability : (4) not assignable 

Original article not reviewed 

19.07.2007 

Type : other 

Deg. product . 

(1)(8) 

Remark : The distinguishing characteristics of methylene urea 

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- -.r . w . 4. Ecotoxicity Id 68611-64-3 

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products versus all other nitrogen fertilizers is their 

availability through the action of soil microorganisms . 

The shorter-chained water-soluble polymers are readily 

digestible by soil microorganisms and release nitrogen to 

the soil as ammonium in a relatively short period of time. 

The longer-chain polymers contain water-insoluble nitrogen, 

which is more slowly digested by soil microorganisms . 

Nitrogen from methylene urea and ureaform is converted 

directly back to the ammonium form gradually throughout the 

growing season. 

Reliability : (4) not assignable 

Product data sheet 

10.07.2007 

4.9 ADDITIONAL REMARKS 

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p. 37 

(6) 
p. 38 

5. Toxicity 

5.0 TOXICOKINETICS, METABOLISM AND DISTRIBUTION 

5.1 .1 ACUTE ORAL TOXICITY 

5.1 .2 ACUTE INHALATION TOXICITY 

5.1 .3 ACUTE DERMAL TOXICITY 

5.1 .4 ACUTE TOXICITY, OTHER ROUTES 

5.2 .1 SKIN IRRITATION 

5.2.2 EYE IRRITATION 

5.3 SENSITIZATION 

5.4 REPEATED DOSE TOXICITY 

5.5 GENETIC TOXICITY'IN VITRO' 

5.6 GENETIC TOXICITY'IN VIVO' 

5.7 CARCINOGENICITY 

5.8.1 TOXICITY TO FERTILITY 

5.8 .2 DEVELOPMENTAL TOXICITYITERATOGENICITY 

5.8 .3 TOXICITY TO REPRODUCTION, OTHER STUDIES 

5.9 SPECIFIC INVESTIGATIONS 

5.10 EXPOSURE EXPERIENCE 

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5. Toxicity 

5.11 ADDITIONAL REMARKS 

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6. Analyt. Meth . for Detection and Identification 

6.1 ANALYTICAL METHODS 

6.2 DETECTION AND IDENTIFICATION 

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p. 41 

7. Eff. Against Target Org. and Intended Uses 

7.1 FUNCTION 

7.2 EFFECTS ON ORGANISMS TO BE CONTROLLED 

7.3 ORGANISMS TO BE PROTECTED 

7.4 USER 

7.5 RESISTANCE 

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8. Meas. Nec. to Prot. Man, Animals, Environment 

8.1 METHODS F1A14DLlWG AND STOtt1ING 

8.2 FIRE GUIDANCE 

8.3 EMERGENCY MEASL4:;NES 

8.4 POSSHL OF ,RENDER11CG SU6ST. HMMILESs 

8.5 WASTE MANAGEMENT 

8.6 SIDE-EFFECTS DETECTION 

8.7 SUBSTANCE RBMT]BRED AS DANGERetJS FOR _9 

8.8 REACTfVfJTY To1VA%RMCEK'fPd"ERAI1TEMA . 

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p. 43 

8. Meas . Nec. to Prot. Man, Animals, Environment 

8.1 METHODS HANDLING AND STORING 

8.2 FIRE GUIDANCE 

8.3 EMERGENCY MEASURES 

8.4 POSSFB. OF RENDERING SUBST~ HARMLESS 

8.5 WASTE MANAGEMENT 

8.6 SIDE-EFFECTS DETECTION 

8.7 SUBSTANCE REGISTERED AS DANGEROUS- FOR GROUND~WATER 

8.8 REACTIVITY TOWARDS CONTAINER MATERIAL 

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p. 44 

9. References Id 68611-64-3 

Date 29.02.2008 

(1) Can. J. Microbiol. 43 (1997) 1111-1117. 

http ://www.orenza.u-psud.fr/query_by_ec.php?EC number--EC%203 

. .3 .21 

(2) Christianson, CB, Carter, MF and Holt, LS (1988) 

Mineralization and Nitrifcation of Ureaform Fertilizers. 

Fertilizer Research, 17: 85-95 

(3) DeJong and DeJonge (1953) as cited in Kaempffe GC and Lunt 

OR (1967) 

(4) Epiwin v3.20 

(5) Hays JT and Haden WW (1966) Soluble fraction of ureaform -

nitrification, leaching and burning. J Ag Food Chem Vol 14 

No 4 pp 339-341 

(6) http ://www.howardfertilizer.com/nugro types.htm 

(7) Jahns, T and Kaltswasser, H (2000) Mechanism ofMicrobial 

Degradation of Slow Release Fertilizers, Journal of Polymers 

and the Environment V 8 No 1, pp 11-16 

(8) Jahns, T., Schepp, R., Kaltwasser, H. Purification and 

characterisation of an enzyme from a strain of Ochrobactrum 

anthropi that degrades condensation products of urea and 

formaldehyde (ureaform). 

(9) Kaempffe GC and Lunt OR (1967) Availability of various 

fractions of urea-formaidehyde. J Agr Food Chem V 15 No 6 pp 

967-971 

(10) Katz, SE and Fassbender, CA (1966) Biodegradability of 

Ureaformaldehydes and Related Compounds. J Agr and Food 

Chemistry V 14, No 4 pp 336-339. 

(11) Long and Winsor (1960) as cited in Kaempffe and Lunt (1967) 

(12) MITI database (2002) (http://www .safe.nite.go.jp/english/db .html) Study published 

2002/11/8 . 

(13) Murray, T.P ., Austin, E.R., Howard, R.G., and Horn R.C. 

Anal. Chem ., vol 54, 1505, 1982. 

(14) The Fertilizer Institute (1983) Formaldehyde Task Group: 

Formaldehyde Use in Urea Based Fertilizers 

(15) The Fertilizer Institute (2007) Personal Communication with 

William Herz, VP, Scientific Affairs, TFI, Washington, DC 

(16) USEPA (1983) 21 C.F .R. § 184.1923 Urea. Title 21 - Food 

and Drugs 

(17) USEPA (2002) http ://www .epa .gov/fedrgstr 

(18) USEPA (2002) http ://www .epa .gov/oppsrrd1/REDs/urea tred .htm 

http://216 .239.51 .104/search?q=cache:p-1264Z8FFIJ:www.fda .go 

vcder/ogd/rld/12154s24.pdf+FDA+category+C+urea&hl=en&ct=clnk 

&d=1 &gl=us 

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p. 45 

9. References 

(19) USEPA (no date specified) AP 42, Fifth Edition, and Volume I 

Chapter 8: Inorganic Chemical Industry 

http ://www.epa.gov/ttn/chief/ap42/ch08/final/c08s02 .pdf 

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10 . Summary and Evaluation 

10.1 END POINT SUMMARY 

10.2 HAZARD SUMMARY 

10.3 RISK ASSESSMENT 

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