Document ID: EPA-HQ-OPPT-2003-0067-0025
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-11-17T05:00Z

PAGE
INTENTIONALLY
LEFT
BLANK
William
C.
Herz
Director
of
Scientific
Programs
M
E
M
O
R
A
N
D
U
M
TO:
Product
Testing
Recipient
FROM:
William
C.
Herz,
Director,
Scientific
Programs
SUBJECT:
Urea
Product
Testing
Dossier
DATE:
March
15,
2003
It
is
with
great
pleasure
that
The
Fertilizer
Institute
(
TFI)
announces
the
completion
and
distribution
of
the
final
product
testing
dossier
for
Urea
(
CAS
#
57­
13­
6).

As
you
are
aware,
TFI
sponsored
this
four
 
year
program
to
develop
and
summarize
screeninglevel
hazard
information
for
high
production
volume
(
HPV)
chemicals.
The
data
elements
generated
represent
a
broad
overview
of
human
health
and
ecological
parameters.
These
include
a
physical
­
chemical
characterization,
environmental
fate,
mammalian
toxicity
and
ecotoxicity.
A
health
and
environmental
safety
data
summary
dossier
was
prepared
for
each
of
the
23
materials.
It
summarizes
the
available
literature
data,
new
testing
data,
category
description
and
read
across
data
as
well
as
provides
a
conclusion
regarding
the
inherent
hazards
of
the
material.

Upon
receipt
of
this
data
a
90
calendar
day
regulatory
trigger
starts
within
which
you
must
update
your
material
safety
data
sheets
(
MS­
DS).
Upon
first
product
shipment
you
must
also
notify
your
distributors
and
employers
once
the
MS­
DS
has
been
updated.
These
regulatory
requirements
are
detailed
in
29
CFR
1910.1200(
g)(
5)
and
29
CFR
1910.1200(
g)(
6)(
i).
The
requirements
are
found
in
the
Occupational
Safety
and
Health
Administration
"
Hazard
Communication
Standard"
(
29
CFR
1910.1200).

Please
note
that
by
receipt
of
this
data;
you
agree
not
to
distribute
or
sell
this
data
beyond
your
own
company.
PAGE
INTENTIONALLY
LEFT
BLANK
HEALTH
&
ENVIRONMENTAL
SAFETY
DATA
SUMMARY
DOCUMENT
UREA
CAS
#
57­
13­
6
Prepared
for
THE
FERTILIZER
INSTITUTE
January
27,
2003
THE
WEINBERG
GROUP
INC.
1220
Nineteenth
St,
NW,
Suite
300
Washington,
DC
20036­
2400
e­
mail
science@
weinberggroup.
com
WASHINGTON
NEW
YORK
SAN
FRANCISCO
BRUSSELS
PARIS
PAGE
INTENTIONALLY
LEFT
BLANK
TABLE
OF
CONTENTS
Page
EXECUTIVE
OVERVIEW...............................................................................................................
1
SIDS
DATA
PROFILE......................................................................................................................
3
SIDS
SUMMARY..............................................................................................................................
4
1.
GENERAL
INFORMATION
...............................................................................................
7
2.
PHYSICAL­
CHEMICAL
DATA
.........................................................................................
16
3.
ENVIRONMENTAL
FATE
AND
PATHWAYS.................................................................
23
4.
ECOTOXICITY....................................................................................................................
27
5.
TOXICITY............................................................................................................................
36
6.
REFERENCES......................................................................................................................
59
1
Urea
(
CAS
#
57­
13­
6)
EXECUTIVE
OVERVIEW
The
Fertilizer
Institute,
on
behalf
of
its
member
companies,
initiated
a
Product
Testing
Project
to
collect,
review,
summarize,
and
where
necessary
develop
additional
health
and
environmental
safety
data
for
23
of
its
high
production
volume
inorganic
fertilizer
materials.
These
data
and
summaries
provide
valuable
information
that
can
be
used
to
update
Material
Safety
Data
Sheets,
answer
customers'
questions,
and
support
product
stewardship
efforts.
The
chemical
industry
is
also
participating
in
a
voluntary
program
of
comparable
scope
for
high
production
volume
organic
chemicals.
1
The
23
fertilizer
materials
were
divided
into
five
categories
(
i.
e.,
ammonia
compounds,
nitrate
compounds,
phosphate
compounds,
salts
and
acids)
based
on
their
primary
constituents
as
shown
in
Table
1.
The
use
of
categories
is
a
recognized
and
accepted
method
that
allows
health
and
environmental
safety
data
from
one
chemical
in
the
category
to
be
used
to
represent
one
or
more
other
related
chemicals
in
the
category.
The
key
is
to
find
similar,
or
at
least
predictable,
patterns
and
trends
among
the
chemicals
in
a
category.
In
this
way,
data
can
be
pooled,
resources
are
optimized,
and
fewer
animals
are
used
in
testing,
all
without
losing
the
ability
to
evaluate
the
hazards
and
safety
of
the
individual
chemicals.
Note
that
some
of
the
materials
fall
into
more
than
one
category
(
e.
g.,
urea
is
in
both
the
nitrate
and
ammonia
categories).

Searches
were
conducted
using
on­
line
databases,
standard
scientific
data
compendia,
and
other
published
sources
for
toxicity,
ecotoxicity,
environmental
fate,
and
physical­
chemical
properties.
The
collected
data
were
reviewed
for
quality
and
acceptability
and
then
summarized
according
to
the
Organization
for
Economic
Cooperation
and
Development
(
OECD)
Screening
Information
Data
Set
(
SIDS)
dossier
format.
The
OECD
countries
(
including
the
United
States)
have
agreed
on
a
set
of
tests
and
on
types
of
data
that
are
generally
necessary
to
characterize
the
chemical
behavior
and
potential
hazards
of
chemicals
released
into
the
environment.
The
OECD
SIDS
dossier
was
chosen
as
a
standard
format
for
the
TFI
Product
Testing
Project
in
order
that
it
would
be
scientifically
defensive,
broadly
applicable
and
easily
understandable
to
a
wide
range
of
stakeholders.

Urea
is
unique
among
the
23
fertilizer
materials
in
that
an
OECD
SIDS
dossier
is
already
available2.
Finland
sponsored
development
of
the
dossier
which
was
published
by
OECD
in
1994.
A
brief
exposure
and
risk
evaluation
was
prepared
in
addition
to
the
health
and
environmental
data
summary.
It
concluded
that
there
was
no
indication
for
concern
for
human
health
and
the
environment
and
that
no
further
testing
was
needed
for
urea.

The
following
pages
provide
the
health
and
environmental
data
from
the
urea
dossier
in
the
same
format
as
the
other
22
fertilizer
materials
and,
in
some
cases,
translated
from
the
original
data
sheets
in
German.
No
additional
searching
for
data
was
conducted.

1
HPV
Chemical
Challenge
Program;
USEPA
1999
(
http://
www.
epa.
gov/
opptintr/
chemrtk/
volchall.
htm)
2
OECD
SIDS
Dossier
 
Urea
(
CAS
#
57­
13­
6)
­
4.5.1994.
60
pages
2
Urea
(
CAS
#
57­
13­
6)
TABLE
1:
CATEGORIES
FOR
PRODUCT
TESTING
PROJECT
CATEGORY
COMPOUND
CAS
NUMBER
Ammonia
Compounds
Anhydrous
ammonia
Aqua
ammonia
Ammonium
nitrate
Ammonium
sulfate
Ammonium
thiosulfate
Nitrogen
solutions
(
UAN)
Ammonium
phosphate
sulfate
Diammonium
phosphate
(
DAP)
Monoammonium
phosphate
(
MAP)
Urea
7664­
41­
7
1336­
21­
6
6484­
52­
2
7783­
20­
2
7783­
18­
8
15978­
77­
5
12593­
60­
1
7783­
28­
0
7722­
76­
1
57­
13­
6
Nitrate
Compounds
Sodium
nitrate
Ammonium
nitrate
Potassium
nitrate
Potassium
sodium
nitrate
Nitrogen
solutions
(
UAN)
7631­
99­
4
6484­
52­
2
7757­
79­
1
7757­
79­
1/
7631­
99­
4
15978­
77­
5
Phosphate
Compounds
Diammonium
phosphate
(
DAP)
Monoammonium
phosphate
(
MAP)
Liquid
polyphosphate
Single
superphosphate**
Granular
triple
superphosphate**
7783­
28­
0
7722­
76­
1
­­
8011­
76­
5
65996­
95­
4
Salts
Potassium
chloride
Potassium
magnesium
sulfate
Potassium
nitrate
Potassium
sodium
nitrate
Potassium
sulfate
Calcium
sulfate
7447­
40­
7
14168­
73­
1
7757­
79­
1
7757­
79­
1/
7631­
99­
4
7778­
80­
5
7778­
18­
9
Acids
Phosphoric
acid
Nitric
acid
Sulfuric
acid
7664­
38­
2
7697­
37­
2
7664­
93­
9
*
=
Nitrogen
solutions
are
represented
largely
by
Urea­
Ammonia­
Nitrogen
(
UAN;
15978­
77­
5)
**
=
Single
superphosphate
and
granular
triple
superphosphate
are
combined
into
a
single
dossier.
­­
=
No
CAS
number
readily
available
3
Urea
(
CAS
#
57­
13­
6)
SIDS
DATA
PROFILE
Date:
April
5,
1994
1.01
A.
CAS
No.
57­
13­
6
1.01
C.
CHEMICAL
NAME
(
OECD
NAME)
Urea
1.01
D
CAS
DESCRIPTOR
Urea
1.01
G
STRUCTURAL
FORMULA
CH4N2O
OTHER
CHEMICAL
IDENTITY
INFORMATION
N/
A
1.5
QUANTITY
World
production
 
41­
60
million
tons
during
1985­
1989
1.7
USE
PATTERN
In
US
 
fertilizer
(
solid
and
solutions)
73%
export
13%
urea
 
formaldehyde
resins
and
adhesives
5%
other
e.
g.,
animal
feeds,
melamine,
consumer
products
9%
1.9
SOURCES
AND
LEVELS
OF
EXPOSURE
Some
manufacturing
and
use
(
e.
g.,
fertilizer
application)
occupational
exposure
possible.
Some
release
to
the
environment
is
likely
during
use.
Maximum
concentration
in
consumer
products
is
generally
1%.
Urea
is
the
end
by
product
of
biochemical
protein
decomposition
and
the
main
solid
component
of
urine.
ISSUES
FOR
DISCUSSION
(
IDENTIFY,
IF
ANY)
No
additional
testing
needed.
4
Urea
(
CAS
#
57­
13­
6)
SIDS
SUMMARY
Date:
April
5,
1994
CAS
No:
57­
13­
6
SPECIES
PROTOCOL
RESULTS
PHYSICAL­
CHEMICAL
DATA
Melting
Point
133oC
Boiling
Point
135oC
(
at
101
kPa)
(
decomposes)
Density
750
kg/
m3
Vapour
Pressure
Calculated
80
Pa
at
20oC
Partition
Coefficient
(
log
Kow)
­
1.59
at
20­
25oC
Water
Solubility
1,193
g/
l
at
25oC
pH
7.2
(
100
g/
l)
Oxidation:
Reduction
potential
­­­
ENVIRONMENTAL
FATE
and
PATHWAY
Photodegradation
­­­
Stability
in
Water
Calculated
T1/
2
>
1
year
Monitoring
Data
­­­
Transport
and
Distribution
Calculated
(
Fugacity
Level
1
type)
In
Air
0.16%
In
Water
99.84%

Biodegradation
OECD
TG
302
B
SCAS
24
hr.
Ultimately
biodegradable
93­
98%
ECOTOXICITY
Acute
toxicity
to
Fish
Barillius
barna
LC50
(
96
hr)
>
9,100
mg/
l
Acute
toxicity
to
Daphnia
Daphnia
magna
DIN
38412
Tell
11
(
modified)
EC50
(
24
hr)
>
10,000
mg/
l
Toxicity
to
Algae
Scenedesmus
quadricauda
Cell
multiplication
inhibition
test
TT
(
192
hr)
>
10,000
mg/
l
Toxicity
to
Soil
Dwelling
Organisms
Applications
of
nitrogenous
fertilizers
to
grassland
for
long
period
may
have
deleterious
effects
on
earthworms
in
the
absence
of
liming.
Toxicity
to
Terrestrial
Plants
Glycine
max
(
L.)
Merr.
Max.
concentration
at
which
no
effect
was
observed
during
the
test
period:
<
0.01
w­
%
urea
of
dry
weight
of
leafs
(=
9
mg/
leaf,
a
7­
day
study)
Toxicity
to
Birds
Pigeon
LDLO
=
16,000
mg/
kg
subcutaneous
TOXICITY
Acute
Oral
Rat
Mouse
Cattle
LD50
=
14,300­
15,000
mg/
kg
LD50
 
11,500­
13,000
mg/
kg
LD50
=
510
mg/
kg
5
Urea
(
CAS
#
57­
13­
6)
CAS
No:
57­
13­
6
SPECIES
PROTOCOL
RESULTS
Acute
Inhalation
­­­
Acute
Dermal
­­­
Mouse
12­
mo
carcinogenicity
screening
NOAEL
=
6750
mg/
kg
Repeated
Dose
Rat
12­
mo
carcinogenicity
screening
NOAEL
=
2250
mg/
kg
Genetic
Toxicity
in
vitro
.
Gene
mutation
Salmonella
Ames
test
­
(
with
metabolic
activation)
­
(
without
metabolic
activation)

Chinese
hamster
fibroblast
Chromosomal
aberration
test
+
at
216
mM
(
without
metabolic
activation)(
very
high
dose)
Mouse
lymphoma
L5178Y/
Tk
+/­
Mouse
lymphoma
TK
locus
assay
+
at
530­
662
mM
+/­
at
265­
379
mM
­
at
132
mM
(
without
metabolic
activation)
.
Chromosomal
aberrations
Mouse
lymphoma
L5178Y/
Tk
+/­
Analysis
of
DNA
singlestrand
breaks
+
at
628­
718
mM
­
at
359­
539
mM
(
without
metabolic
activation)
Genetic
Toxicity
in
vivo
Mouse
Bone
marrow
cytogenetic
test
+
7­
fold
rate
of
aberrations
compared
to
controls;
mice
were
fed
with
urea
500
mg
per
animal
per
day
for
5
days
(
extremely
high
dose)
Mouse
Long
term
Not
carcinogenic
Carcinogenicity
Rat
dietary
studies
Not
carcinogenic
Mouse
12­
month
carcinogenicty
screening
No
toxic
effects
in
gonads
reported
at
dose
levels
up
to
6750
mg/
kg/
d
Reproduction
Toxicity
Rat
12­
month
carcinogenicity
screening
No
toxic
effects
in
gonads
reported
at
dose
levels
up
to
2250
mg/
kg/
d
Development/
Teratogenicity
Rat
Urea
(
50
g/
kg/
d)
was
given
in
2
doses
12
h
apart
by
gavage
for
an
average
of
14
days
No
outstanding
(
external)
teratogenicity
was
noted,
the
mean
birthweight
was
lower
but
the
litter
size
was
greater
Skin
Irritation
Human
Experience
May
be
irritating
at
>
10%
concentration;
not
a
skin
sensitizer
6
Urea
(
CAS
#
57­
13­
6)
CAS
No:
57­
13­
6
SPECIES
PROTOCOL
RESULTS
Human
Experience
Despite
extensive,
long
term
use
in
dermatology,
no
contact
allergy
or
marked
side
effects
have
been
reported.
Human
SLADH
patients
receiving
urea
orally
(
30
g/
d)
up
to
5
years
did
not
exhibit
side
effects
7
Urea
(
CAS
#
57­
13­
6)
1.
GENERAL
INFORMATION
1.01
SUBSTANCE
INFORMATION
*
A.
CAS
number
57­
13­
6
B.
Name
(
IUPAC
name)
Urea
*
C.
Name
(
OECD
name)
Urea
*
D.
CAS
Descriptor
(
where
applicable
for
complex
chemicals)

E.
EINECS
Number
200­
315­
5
F.
Molecular
Formula
CH4N2O
*
G.
Structural
Formula
H2N\
C=
O
H2N/

H.
Substance
Group
<
text
begins
here>
(
If
possible,
only
for
petroleum
products,
see
HEDSET
explanatory
note)

I.
Substance
Remark
<
text
begins
here>
(
Indicate
the
substance
remark
as
prescribed
in
the
EINECS
Inventory,
if
possible)

J.
Molecular
Weight
60.06
1.02
OECD
INFORMATION
A.
Sponsor
Country
Finland
B.
Lead
Organization
Name
of
Lead
Organization:
National
Board
of
Waters
and
the
Environment
Contact
Person:
Mr.
Jukka
Malm
Address/
Phones:
P.
O.
B.
250
SF­
00101
Helsinki
FINLAND
Tel:
+
358­
0­
69­
51­
388
Fax:
+
358­
0­
69­
51­
381
8
Urea
(
CAS
#
57­
13­
6)
C.
Name
of
Responder
(
Information
on
a
responder
should
be
provided
when
companies
respond
to
Lead
Organization
or
SIDS
Contact
Points.)

Name:
Mr.
Jukka
Malm
Address/
Phones:
P.
O.
B.
250
SF­
00101
Helsinki
FINLAND
Tel:
+
358­
0­
69­
51­
388
Fax:
+
358­
0­
69­
51­
381
1.1
GENERAL
SUBSTANCE
INFORMATION
A.
Type
of
Substance
element
[
];
inorganic
[
X];
natural
substance
[
X];
organic
[
];
organometallic
[
];
petroleum
product
[
]
Urea
is
considered
an
organic
compound
by
some
regulatory
agencies.

B.
Physical
State
(
at
20
°
C
and
1.013
hPa)

gaseous
[
];
liquid
[
];
solid
[
X]

C.
Purity
98­
99
wt
%
(
Indicate
the
percentage
by
weight/
weight)

1.2
SYNONYMS
Carbamide
Carbonyl
diamide
1.3
IMPURITIES
[
Indicate
CAS
No.,
chemical
name
(
IUPAC
is
preferable),
percentage,
if
possible
EINECS
number.]

CAS
No.:
EINECS
No.:
Name:
Biuret
Value:
0.3
 
2
wt
%
Remarks:
Kirk­
Othmer
Encyclopedia
Name:
Methylenediurea
Value:
1.3­
2.2%
Remarks:
Testing
results
indicate
that
inclusion
of
these
materials
does
not
adversely
affect
toxicity.
9
Urea
(
CAS
#
57­
13­
6)
1.4
ADDITIVES
[
e.
g.
stabilizing
agents,
inhibitors
etc.
Indicate
CAS
No.,
chemical
name
(
IUPAC
name
is
preferable),
percentage,
if
possible
EINECS
number,
the
component
of
the
UVCB
substance
with
no
defined
composition)
should
be
indicated
here.]

CAS
No.:
EINECS
No.:
Name:
Urea­
formaldehyde
binder
can
be
used
in
some
prilling
processes
Value:
<
text>
Remarks:
<
text>

*
1.5
QUANTITY
[
Information
on
production
or
import
levels
should
be
provided
in
figures
or
ranges
(
e.
g.
1,000­
5,000;
5,000­
10,000
tonnes,
etc.;
see
SIDS
Manual)
per
responder
or
country
and
the
date
for
which
those
ranges
apply
should
be
given.
For
EU
Member
states,
only
indicate
the
EU
import
figure.
Give
an
estimation
of
the
global
production
quantity
in
the
remarks
field.
Information
on
the
number
of
producers
in
the
country
and
the
source
of
information
should
also
be
given
in
the
remarks
field.)

Remarks:
Production
figures
(
1985­
1989)
in
metric
tons
N
USA
1,470,000
 
2,350,000
Total
NA
3,140,000
 
6,278,000
Total
SA
644,000
 
949,000
Total
Asia
8,063,500
 
12,185,000
Total
Europe
7,144,900
 
8,321,000
World
Total
19,062,400
 
27,963,000
(
as
urea)
41,440,000
 
60,789,000
(
urea
N
 
46%)
References:
FAO
Yearbook,
Fertilizer,
1990
1.6
LABELING
AND
CLASSIFICATION
(
If
possible,
enter
information
on
labeling
and
classification,
such
as
labeling
and
classification
system,
existence
of
specific
limit,
symbols,
nota,
R­
Phrases
and
S­
Phrases
of
EC
Directive
67/
548/
EEC.
See
HEDSET
Explanatory
Note.)

Labeling
Type:
<
text>
Specific
limits:
None
Symbols:
<
text>
Nota:
<
text>
R­
phrases:
None
S­
phrases:
None
Text
of
S­
phrases:
<
text>
Remarks:
<
text>

Classification
Type:
<
text>
10
Urea
(
CAS
#
57­
13­
6)
Category
of
danger:
<
text>
R­
phrases:
<
text>
Remarks:
<
text>

Recommended
precautions
and
summary
of
safety
data
sheets
Main
hazardous
properties:
Pure,
uncontaminated
urea
is
a
stable,
safe
product
to
handle.
It
does
not
pose
a
toxicity,
fire
or
explosion
problem
and
is
not
generally
considered
hazardous
when
exposed
to
open
flame.
It
does
not
polymerize.
However,
instability
can
result
with
exposure
to
hypochlorites.
An
unstable
explosive
compound
(
nitrogen
trichloride)
can
result.

Incompatibilities
with
gallium
perchlorate,
permanganate,
dichromate,
nitrate
and
chlorine
exist.
Avoid
contact
with
caustics
and
alkalies.
Urea
may
form
cyanuric
acid,
HOCNC(
OH)
NC(
OH)
N2H2O,
in
aqueous
solutions
at
elevated
temperatures.
In
the
presence
of
strong
alkalies
at
elevated
temperatures,
urea
can
form
metal
cyanates
that,
if
swallowed,
can
be
metabolized
in
the
body
to
form
toxic
cyanides.

Fire:
Urea
has
no
fire
or
explosion
hazards
unless
it
is
heated
to
the
point
of
decomposition
whereby
flammable
gas
can
be
given
off.
The
compound
is
not
generally
considered
hazardous
if
exposed
to
open
flame.
Urea
dust
clouds
have
been
reported
to
withstand
a
temperature
of
900oC
(
1650
F)
without
igniting.

Human
health:
Urea
is
not
considered
toxic
to
humans
or
animals,
although
certain
individuals
experience
skin
sensitivity.
It
is
a
diuretic
and
a
topical
keratolytic
and
antiseptic.
The
major
health
hazard
is
the
possibility
of
skin
burns
on
contact
with
molten
urea
during
processing
or
in
case
of
fire.

Excessive
inhalation
of
dust
may
cause
irritation,
coughing
and
labored
breathing
(
especially
workers
with
asthma).
Urea
is
irritant
to
the
eyes
and
mucous
membranes.
Prolonged
skin
contact
may
cause
mild
irritation
and
redness.
Ingestion
can
cause
nausea,
gastric
irritation,
diarrhea
and
stomach
pain.
Individuals
with
kidney
impairment
or
asthmatic
condition
should
have
physician's
approval
before
working
with
urea
dust.

Environment:
Large
spills
can
contaminate
soil,
surface
and
ground
water.

Storage:
The
problems
associated
with
urea
bulk
storage
are
primarily
related
to
incompatibility
with
other
fertilizer
products.
Urea
itself
is
hygroscopic
when
humidity
is
over
75
percent,
picking
up
water
readily
from
humid
atmospheres.
When
urea
becomes
contaminated
with
other
fertilizer
materials,
particularly
with
ammonium
nitrate
or
phosphate
fertilizers,
its
hygroscopicity
is
sharply
increased,
presently
serious
pile
setting
and
caking
problems.

Handling
precautions:
Use
good
housekeeping
techniques
that
will
facilitate
keeping
airborne
particulates
and
dust
deposits
at
a
minimum.
Avoid
breathing
urea
dust.
Avoid
prolonged
or
repeated
skin
contact.
Practice
good
personal
hygiene
daily
to
minimize
industrial
dermatitis
11
Urea
(
CAS
#
57­
13­
6)
and/
or
irritation.
(
Remove
work
clothes
and
shower
before
going
home
daily).
Keep
urea
away
from
food
and
beverage.

When
hopper
cars
or
bulk
trucks
loaded
with
liquid
or
solid
urea
are
opened,
ammonia
vapor
and
carbon
dioxide
may
accumulate
above
the
product.
Enter
hoppers
or
vessels
only
after
removing
any
vapor
accumulations
by
proper
ventilation.

Personal
protection:
Use
protective
gloves
or
skin
barrier
cream
to
avoid
skin
rash
or
irritation.
High
concentrations
of
dust
call
for
the
use
of
protective
dust
respiratory
devices.
When
work
is
performed
around
urea­
processing
areas,
hot
liquid
or
airborn
dust
particles
may
escape;
therefore,
use
appropriate
personal
protective
equipment.
Workers
should
use
a
face
shield
or
chemical
goggles,
rubber
elbow­
length
gloves
and
a
rubber
rain
suit
in
such
environments.
Workers
should
wear
rubber
footwear
since
urea
solutions
are
very
corrosive
to
leather.

First
aid:
Skin
burns:
If
molten
urea
is
spilled
on
the
skin,
flush
with
water
to
remove
the
heat
from
the
urea,
which
would
otherwise
continue
to
produce
skin
burns
until
cooled.
Then
wash
gently
with
mild
soap
and
water.
Send
victim
to
physician
to
have
burned
area
examined.

Eye
contact:
Hold
eyes
open
and
flush
thoroughly
with
running
water
for
15­
20
minutes.
If
any
irritation
or
redness
persists,
see
a
physician
or
ophthalmologist.

Skin
contact:
Wash
affected
area
thoroughly
with
soap
and
water.
Remove
all
contaminated
clothing.
If
serious
conditions
persist,
see
physician
or
dermatologist.

Inhalation:
Remove
victim
to
fresh
air
to
restore
or
support
breathing.
Administer
oxygen
is
breathing
is
still
labored.
For
persisting
conditions,
consult
a
physician.

Ingestion:
Have
victim
drink
2
L
of
water
or
saline
solution
to
dilute
stomach
contents.
Seek
medical
help
for
further
treatment,
observation
and
support
after
first
aid.

Extinguishing:
Fire
fighters
should
wear
self
contained
breathing
apparatus
in
fires
where
urea
is
being
stored.
Thermal
and
oxidative
degradation
products
can
include
ammonia,
cyanuric
acid,
biuret
and
carbon
dioxide.

Spillage
and
disposal
procedure:
Spill
and
leak
procedures
for
urea
are
as
follows:
Sweep
up
or
scoop
up
spilled
material
for
recovery
or
disposal.
Using
a
dedusting
agent
(
sweeping
compound,
moist
sand,
etc.)
and
ventilating
the
area
are
recommended
to
keep
dust
levels
low.
Avoid
contamination
of
spilled
urea
with
oxidizing
agents
or
nitrates.
Flush
residue
with
copious
water.
Treat
airborne
urea
dust
by
using
a
fine
water
spray
and
local
ventilation.

Small
leaks
and
spills
of
urea
to
aqueous
environments
are
generally
handled
by
diluting
the
urea­
water
mix
and
discharging
into
the
waste
stream.

Large
leaks
or
spills
to
aqueous
environments
entail
recycling
and
reprocessing
the
ureacontaminated
water
to
regenerate
the
spilled
urea.
(
Once
again,
note
and
avoid
incompatibilities.)
12
Urea
(
CAS
#
57­
13­
6)
Dispose
of
urea
wastes
and
spills
by
burial
in
an
approved
landfill
or
possibly
spread
on
farmland
as
fertilizer
(
provided
other
contaminants
allow
this
use).
Incineration
is
another
option.
Use
a
licensed
waste
hauler,
documenting
all
procedures,
destinations,
etc.
Make
sure
the
urea
waste
is
disposed
of
in
accordance
with
federal,
state
or
local
regulations,
following
the
strict
regulations.
Reference:
National
Safety
Council,
UREA:
Safe
Use
and
Handling,
Data
Sheet
I
 
691
Rev.
90.

*
1.7
USE
PATTERN
A.
General
[
Data
on
use
pattern
have
to
be
given
by
assigning
main
types
according
to
their
exposure
relevance
(
i.
e.
non­
dispersive
use,
use
in
closed
systems,
use
resulting
in
inclusion
into
or
onto
matrix
and
wide
dispersive
use),
industrial
categories
(
e.
g.
basic
chemical
industry,
chemical
industry,
agricultural
industry,
personal
and
domestic
use)
and
use
categories
such
as
coloring
agents,
intermediates,
solvents,
adhesives,
cleaning/
washing
agents,
fertilizers,
impregnation
agents,
surface­
active,
etc.
If
available,
give
an
estimation
of
different
uses
in
percentage
terms.
See
SIDS
Manual
for
guidance.]

Type
of
Use:
Category:

(
a)
main
nitrogenous
fertilizer
industrial
use
(
b)
main
animal
feed
supplement
at
approximately
1%
of
ration
industrial
use
Remarks:
(
a)
Manufacturing
and
use
in
industry:
In
modern
synthetic
processes,
urea
is
made
by
reacting
ammonia
and
carbon
dioxide
at
high
pressure
and
high
temperature
to
form
ammonium
carbamate
and
simultaneously
dehydrating
the
ammonium
carbamate
to
urea
and
water.
Produced
urea
is
purified
by
crystallization.

Occupational
and
environmental
exposure
during
production
is
possible
due
to
accidental
process
breakdowns
and
disorders
in
reactor
operations,
pumping
cycles,
evaporation
and
crystallization
processes,
in
maintenance,
loading
and
unloading
operations.
Potential
occupational
exposure
occurs
via
inhalation
of
aerosols
from
urea
melt
and
hot
saturated
solutions,
or
splashes
to
skin
or
eyes,
or
inhalation
of
dust.

Consumption
patterns
in
USA:
13
Urea
(
CAS
#
57­
13­
6)
Fertilizer,
solid
42%
fertilizer
solutions
31%;
exports
13%;
ureaformaldehyde
resins
and
adhesive
5%;
other,
including
animal
feeds
and
melamine
9%.

(
b)
<
text>

Reference:
Vershueren,
K.
Handbook
of
Environmental
Data
on
Organic
Chemicals,
2nd
Edition.
Van
Nostrand
Reinhold,
1983.
p.
1178.
Altman,
P.
L.
and
Dittmar,
D.
S.
1974.
Biology
Data
Book,
Vol.
III,
2nd
Ed.
Federation
of
American
Societies
for
Experimental
Biology.
p.
1494.

B.
Uses
in
Consumer
Products
[
If
the
chemical
is
present
in
consumer
products
as
marketed,
give
details
of
products'
function
(
e.
g.
detergent,
etc.),
and
percentage
in
product
and
physical
state
of
product
as
marketed
(
e.
g.
aerosol,
powder
or
liquid)]

Function
Amount
present
Physical
State
Cleaning
products,
Up
to
1%
Varies
cosmetics,
foods
Remarks:
Urea
is
used
in
liquid
soaps,
detergents
and
household
cleaning
products.
It
is
also
used
in
cosmetics
products
as
creams,
shampoos,
hair
conditioners,
hair
dyes
and
dye
removers,
in
ammoniated
dentifrices
etc.
Maximum
urea
concentration
is
commonly
1%.
Urea
peroxide
(
10­
15%)
preparations
for
tooth
bleaching
yield
urea
(
6.4­
9.6%
of
weight).

Urea
is
a
natural
constituent
of
many
common
foodstuffs.
Oats
may
contain
4.5
percent
of
their
total
nitrogen
content
as
urea
and
oil
seed
meals
about
0.25
percent.
Up
to
15
percent
of
the
total
nitrogen
of
young
plants
and
about
5
percent
of
the
mature
plants
is
nonproteinaceous
and
much
is
in
the
form
of
urea.
Urea
is
a
normal
constituent
of
animal
tissues
and
fluids
and
is
ingested
in
small
amounts
when
meat
is
consumed.
References:
Svensson,
Kaj
and
Yhdistys,
Suomen
Teknokemian
(
Cosmetics
and
Detergent
Association
in
Finland),
May
1992.
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.
Fasanaro,
T.
S.
1992.
Bleaching
teeth:
History,
chemicals
and
methods
used
for
common
tooth
discolorations.
J
Esthet
Dent.
4:
71­
78.
14
Urea
(
CAS
#
57­
13­
6)
1.8
OCCUPATIONAL
EXPOSURE
LIMIT
VALUE
(
Indicate
the
type
of
occupational
exposure
limit
value
including
short­
term
exposure
limit
value.
If
a
value
does
not
exist,
give
the
hygiene
standard
of
the
producer
company
if
available.
See
also
5.11.)

OSHA
permissible
exposure
levels:
15
mg/
m3
total
dust
5
mg/
m3
respirable
dust
Exposure
limit
value
Type:
OSHA
PEL
Value:
15
mg/
m3
total
dust;
5
mg/
m3
respirable
fraction
Remark:
No
specific
limit
has
been
set
for
urea,
however,
the
federal
OSHA
PEL
for
particulates
not
otherwise
regulated
applies
to
all
fertilizer
dusts.
In
addition,
AIHA
established
of
Workplace
Environmental
Exposure
Limit
(
WEEL)
of
10
mg/
m3
as
a
nonregulatory
guidance
number.
Regulated
limits
may
vary
in
local
jurisdictions.

Short
term
exposure
limit
value
Value:
Not
hazardous;
however,
the
general
guidance
(
EH40
UK
Health
and
Safety
Executive)
is
that
personal
exposure
to
dust
should
be
controlled
to
<
10
mg/
m3
(
8
hr
TWA)
for
inhalable
dust
and
<
5
mg/
m3
(
8
hr
TWA)
for
respirable
dust.
Length
of
exposure
period:
<
text>
Frequency:
<
text>
Remarks:
<
text>
Reference:
EFMA
Website.
Booklet
No.
5
of
8:
Production
of
Urea.
7.
Occupational
Health
and
Safety.
Vershueren,
K.
1983.
Handbook
of
Environmental
Data
on
Organic
Chemicals,
2nd
ed.
Van
Nostrand
Reinhold,
New
York.
p.
1178.

*
1.9
SOURCES
OF
EXPOSURE
Describe
sources
of
potential
human
[
other
than
concentration
of
chemicals
in
the
workplace
and
indoor
environment
(
see
5.11)],
or
environmental
exposure,
including
emission
data
(
e.
g.
quantities
per
media
with
information
such
as
time
dimensions
of
release,
indication
of
type
of
release
(
e.
g.
point
source
or
diffuse),
type
of
estimating
(
e.
g.
average
or
worst
case,
uncertainties
in
estimation),
for
all
phases
of
the
life
cycle
of
the
chemical
if
available,
including
manufacturing
and
user
areas.

For
environmental
exposure,
indicate
the
production
process
briefly,
number
the
sites
of
manufacture
and,
the
basis
for
concluding
that
the
process
is
"
closed"
if
applicable.

Also
an
indication
of
measured
exposure
levels
(
expressed
in
an
appropriate
form,
e.
g.
geometric
mean
and
standard
deviation)
can
be
mentioned
here.
Any
information
that
15
Urea
(
CAS
#
57­
13­
6)
will
help
focus
the
assessment
of
exposure
(
either
qualitative
or
quantitative
in
nature)
can
be
mentioned,
if
available).

Source:
Media
of
release:
<
text
here>
Probable
human
exposure:
The
National
Occupational
Hazard
Survey
conducted
by
NIOSH
estimated
that
in
the
USA
855
894
workers
may
be
exposed
to
urea;
7%
from
actual
observed
use,
31%
from
observed
use
of
a
treadename
product
known
to
contain
this
chemical,
and
62%
from
observed
use
of
product
in
some
type
of
general
use
which
leads
NIOSH
to
suspect
that
chemical
may
be
contained
in
the
product.
[
NIOSH
National
Hazard
Exposure
Survey
(
1972­
1974);
as
cited
in
HSDB
1991].
Remarks:
Exposure
in
farming:
The
use
of
highly
concentrated
fertilizers
in
agriculture
practice
and
in
gardens
can
lead
to
human,
livestock
and
pet
exposure.
Sources
of
exposure
may
be
accidental
inclusions
of
highly
concentrated
fertilizers
in
rations,
application
of
fertilizers
to
fields
with
livestock,
or
washing
of
recently
applied
fertilizers
by
rain
into
water
supplies
of
livestock.
In
some
instances
granular
or
liquid
fertilizers
may
be
accidentally
spilled
on
land
or
into
ponds,
and
in
other
instances
fertilizer
containers
may
be
used
for
watering
livestock
without
thorough
cleaning
and
removal
of
residual
fertilizers.

Environmental
exposure:
Various
species
of
wild
animals
are
exposed
to
urea
when
urea
fertilizers
are
spread
directly
on
the
field
and
in
the
forests.
Aquatic
organisms
are
exposed
to
urea
when
recently
applied
fertilizers
are
washed
by
rain
into
rivers,
lakes
and
seas.

Emission
to
soil:
About
80%
of
produced
urea
is
used
as
a
fertilizer.
Urea
production
capacities
are
expected
to
increase
rapidly
after
1992.

Emission
to
air:
Urea
is
essentially
non­
volatile.
References:
Oehme,
F.
W.
and
Barrel,
D.
S.
1986.
Veterinary
Gastrointestinal
Toxicology,
Chapter
17
in
Rozman,
K.
and
Hänninen,
O.
(
eds.),
Gastrointestinal
Toxicology,
Elsevier
Science
Publishers,
Amsterdam.
p.
489­
490.
Informations
Chimie
No.
315,
Mars
1990.
p.
179­
201.
Environmental
Canada:
Tech
Info
for
Problem
Spills:
Urea.
1985.
p.
21
as
cited
in
HSDB
1991.

1.10
ADDITIONAL
REMARKS
16
Urea
(
CAS
#
57­
13­
6)
A.
Options
for
disposal
[
Mode
of
disposal
(
e.
g.
incineration,
release
to
sewage
system,
etc.)
for
each
category
and
type
of
use,
if
appropriate;
recycling
possibility.]

Remarks:
Small
leaks
and
spills
of
urea
to
aqueous
environments
are
generally
handled
by
diluting
the
urea­
water
mix
and
discharging
into
the
waste
stream.
Large
leaks
or
spills
to
aqueous
environment
entail
recycling
and
reprocessing
the
urea­
contaminated
water
to
regenerate
the
spilled
urea.
(
Note
and
avoid
incompatibilities.)

Water
Spill:
Contain
by
damming,
water
diversion
or
natural
barriers.
Remove
and
treat
contaminated
liquids.
Absorb
small
amounts
of
liquid
spill
with
natural
or
synthetic
sorbents,
shovel
into
containers
and
cover.

Landfill:
Waste
may
be
buried
in
an
approved
landfill
or
spread
on
farmland
as
fertilizer
(
if
other
contaminants
will
allow
this
use).
Incineration
is
another
option.
Use
a
licensed
waste
hauler,
documenting
all
procudures,
destinations,
etc.
Make
sure
the
urea
waste
is
disposed
of
in
accordance
with
federal,
state
or
local
regulations
following
the
strictest
regulations.
References:
National
Safety
Council,
UREA:
Safe
Use
and
Handling.
Data
Sheet
I­
691
Rev.
90.
Environment
Canada.
1985.
Tech
Info
for
Problem
Spills:
Urea.
p.
2;
as
cited
in
HSDB
1991.
United
Nations,
Treatment
and
Disposal
Methods
for
Waste
Chemicals
(
IRPTC
File),
Date
Profile
Series
No.
5.
Geneva,
Switzerland:
United
Nations
Environmental
Programme,
Dec.
1985,
p.
295;
as
cited
in
HSDB
1991.

B.
Other
remarks
Remarks:
<
text
here>
References:
<
text
here>

2.
PHYSICAL­
CHEMICAL
DATA
*
2.1
MELTING
POINT
(
If
more
than
one,
identify
the
recommended
value.)

Value:
132.7
°
C;
133oC
Decomposition:
Yes
[
X]
No
[
]
Ambiguous
[
]
Sublimation:
Yes
[
]
No
[
X]
Ambiguous
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Not
mentioned
17
Urea
(
CAS
#
57­
13­
6)
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
On
further
heating
decomposes
to
biuret,
NH3
and
cyanuric
acid.
On
standing
or
on
heating
decomposes
to
NH3
and
CO2.
References:
The
Merck
Index,
11th
ed.,
Rahway,
NJ.,
USA,
Merck
&
Co.,
Inc.
1989.
#
9781.
BASF
AG,
AIDA,
Grunddatensatz
aus
urea.
1991.
Unpublished.
KEMIRA
B.
V.,
Technical
Information
Data
Sheet.
1998.
Unpublished.
Osol,
A.,
Hoover,
J.
E.,
et
al.
(
eds.)
Remington's
Pharmaceutical
Sciences,
15th
ed.,
Easton,
Pennsylvania,
Mack
Publishing
Co.
1975.
p.
864;
as
cited
in
HSDB
1991.

*
2.2
BOILING
POINT
(
If
more
than
one,
identify
the
recommended
value.)

Value:
135
°
C
Pressure:
at
101kPa
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Not
mentioned
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
Urea
decomposes
before
boiling
References:
BASF
AG,
AIDA,
Grunddatensatz
aus
urea.
1991.
Unpublished
Environment
Canada.
1985.
Tech
info
for
problem
spills:
urea.

*
2.3
DENSITY
(
Relative
Density)
(
Where
applicable,
indicate
the
relative
density
of
the
substance.)

Type:
Bulk
density
[
X];
Density
[
];
Relative
Density
[
]
Value:
750
kg/
m3
Temperature:
°
C
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Not
mentioned
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
Specific
gravity
1323
kg/
m3
at
20­
24oC
Density
of
water
solution
1057
kg/
m3
10%
(
w/
w)
References:
Weast,
R.
C.
(
ed.).
1979.
Handbook
of
Chemistry
and
Physics.
60th
ed.
Boca
Raton,
Florida:
CRC
Press,
Inc.
p.
c­
536;
as
cited
in
HSDB
1991.
The
Merck
Index,
11th
ed.
1989.
Rahway,
N.
J.,
USA,
Merck
&
Co.,
Inc.
#
9781.
18
Urea
(
CAS
#
57­
13­
6)
*
2.4
VAPOUR
PRESSURE
(
If
more
than
one,
identify
the
recommended
value)

(
a)
Value:
80
Pa
Temperature:
20
°
C
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Calculated
[
X];
measured
[
]
Calculated
according
to
Lyman
et
al.
1990.
Handbook
of
Chemical
Property
Estimation
Methods.
American
Chemical
Society,
Washington.
GLP:
Yes
[
]
No
[
X]
?
[
]
Remarks:
<
text>
References:
National
Board
of
Waters
and
the
Environments.
1993.
Unpublished
data.

(
b)
Value:
1.73
KPa,
5.33
KPa
Temperature:
20
and
40
°
C
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Calculated
[
];
measured
[
]
Not
known;
saturated
water
solutions
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
The
values
are
graphically
evaluated
from
the
vapour
pressure
density
diagram
of
urea
water
solutions
presented
in
the
reference.
References:
Environment
Canada.
1985.
Tech.
info.
for
problem
spills:
Urea.
p.
4
as
cited
in
HSDB
1991.
Kemira,
B.
V.
1988.
Technical
Information
Data
Sheet.
p.
9
(
Unpublished).

*
2.5
PARTITION
COEFFICIENT
logPow
(
If
more
than
one,
identify
the
recommended
value)

(
a)
Log
Pow:
­
1.59
Temperature:
20­
25
°
C
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Calculated
[
];
measured
[
X]
OECD
Test
Guideline
107,
Flask­
shaking
method.
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
The
value
of
log
Pow
is
given
as
reference
substance
value
in
OECD
Test
Guideline
Method
107.
19
Urea
(
CAS
#
57­
13­
6)
References:
OECD
Test
Guideline
for
Testing
Materials.
1981.
Method
107,
Paris.

(
b)
Log
Pow:
­
2.97/­
2.26
­
2.59
Temperature:
°
C
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Calculated
[
X];
measured
[
]
Increment
method
von
Rekker
with
computer
program
of
Compudrug
Ltd.
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
e.
g.,
is
the
compound
surface
active
or
dissociative?
References:
Vershueren,
K.
1983.
Handbook
of
Environmental
Data
on
Organic
Chemicals,
2nd
ed.
Van
Nostrand
Reinhoild,
NY.
p.
1178.
BASF
AG,
AIDA,
Grunddatensatz
aus
urea,
1991,
p.
2.
Unpublished.

*
2.6
WATER
SOLUBILITY
(
If
more
than
one,
identify
the
recommended
value)

A.
Solubility
Value:
780,000;
1,080,000;
1,193,000;
7,330,000
mg/
L
Temperature:
5
°
C;
20oC;
25oC;
100oC
Description:
Miscible
[
];
Of
very
high
solubility
[
];
Of
high
solubility
[
X];
Soluble
[
];
Slightly
soluble
[
]
Of
low
solubility
[
];
Of
very
low
solubility
[
];
Not
soluble
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Not
mentioned
GLP:
Yes
[
]
No
[
]
?
[
X]
Remarks:
<
text>
References:
BASF
AG
AIDA.
1991.
Grunddatensatz
aus
urea.
p.
2
Unpublished.
Vershueren,
K.
1983.
Handbook
of
Environmental
Data
on
Organic
Chemicals,
2nd
ed.,
Van
Nostrand
Reinhold,
NY.
p.
1178.
Weast,
R.
C.
(
ed.).
1979.
Handbook
of
Chemistry
and
Physics.
60th
ed.
Boca
Raton,
Florida:
CRC
Press
Inc.,
1979,
p.
c­
536;
as
cited
in
HSDB
1991.

B.
pH
Value,
pKa
Value
pH
Value:
7.2
and
9.5
Concentration:
100,000
mg/
L
(
water)
200,000
mg/
L
(
water)
20
Urea
(
CAS
#
57­
13­
6)
Temperature:
°
C
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Not
mentioned
GLP:
Yes
[
]
No
[
]
?
[
X]
(
Where
applicable,
enter
values
for
the
dissociation
constant(
s)
and
the
conditions
under
which
they
were
measured.)
pKa
value
<
text>
at
25
°
C
Remarks:
<
text>
References:
The
Merck
Index,
11th
ed.,
Rahway,
NJ,
USA.
1989.
#
9781.
KEMIRA
B.
V.,
Technical
Information
Data
Sheet.
1988.
Unpublished.

2.7
FLASH
POINT
(
liquids)

Value:
°
C
Type
of
test:
Closed
cup
[
];
Open
cup
[
];
Other
[
]
Method:
(
with
the
year
of
publication
or
updated
of
the
method
used)
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Remarks:
<
text>
References:
<
text>

2.8
AUTO
FLAMMABILITY
(
solid/
gases)

Value:
°
C
Pressure:
<
text>
hPa
Method:
(
with
the
year
of
publication
or
updated
of
the
method
used)
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Remarks:
Non­
flammable
and
non­
combustible
References:
Hawley,
G.
G.
1977.
The
Condensed
Chemical
Dictionary,
9th
ed.,
New
York,
Van
Nostrand
Reinhold
Co.
p.
905.

2.9
FLAMMABILITY
Results:
Extremely
flammable
[
];
Extremely
flammable
 
liquified
gas
[
];
Highly
flammable
[
];
Flammable
[
];
Non
flammable
[
X];
Spontaneously
flammable
in
air
[
];
Contact
with
water
liberates
highly
flammable
gases
[
];
Other
[
]
21
Urea
(
CAS
#
57­
13­
6)
Method:
(
with
the
year
of
publication
or
updated
of
the
method
used)
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Remarks:
<
text>
References:
Hawley,
G.
G.
The
Condensed
Chemical
Dictionary,
9th
ed.
New
York,
Van
Nostrand
Reinhold
Co.
1977.
p.
905.

2.10
EXPLOSIVE
PROPERTIES
Results:
Explosive
under
influence
of
a
flame
[
];
More
sensitive
to
friction
than
m­
dinitrobenzene
[
];
More
sensitive
to
shock
than
m­
dinitrobenzene
[
];
Not
explosive
[
X];
Other
[
]
Method:
(
with
the
year
of
publication
or
updated
of
the
method
used)
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Remarks:
<
text>
References:
National
Safety
Council,
Urea:
Safe
Use
and
Handling,
Data
Sheet
I­
691.
Rev.
90.

2.11
OXIDIZING
PROPERTIES
Results:
Maximum
burning
rate
equal
or
higher
than
reference
mixture
[
];
Vigorous
reaction
in
preliminary
test
[
];
No
oxidizing
properties
[
];
Other
[
]
Method:
(
with
the
year
of
publication
or
updated
of
the
method
used)
<
text>
GLP:
Yes
[
]
No
[
]
?[
]
Remarks:
<
text>
References:
<
text>

*
2.12
OXIDATION:
REDUCTION
POTENTIAL
(
Where
applicable,
indicate
the
redox
potential
and
the
conditions
under
which
it
was
measured.)

Value:
<
text>
mV
Method:
(
with
the
year
of
publication
or
updated
of
the
method
used)
<
text>
GLP:
Yes
[
]
No
[
]
?[
]
Remarks:
<
text>
References:
<
text>
22
Urea
(
CAS
#
57­
13­
6)
2.13
ADDITIONAL
DATA
A.
Partition
co­
efficient
between
soil/
sediment
and
water
(
Kd)

Value:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?[
]
Remarks:
<
text>
References:
<
text>
23
Urea
(
CAS
#
57­
13­
6)
B.
Other
data
[
e.
g.
Henry's
Law
constant,
fat
solubility,
surface
tension
(
of
aqueous
solution),
adsorption/
desorption
on
soil,
particle
size
distribution,
etc.]

Results
<
text>
Remarks:
<
text>
References:
<
text>

3.
ENVIRONMENTAL
FATE
AND
PATHWAYS
[
Reporting
of
studies
should
give
the
test
method,
test
conditions,
(
laboratory
versus
field
studies),
test
results
(
e.
g.
%
degradation
in
specified
time
period)
and
reference.
Information
on
breakdown
products
(
transient
and
stable)
should
be
provided
when
available.]

3.1
STABILITY
*
3.1.1
PHOTODEGRADATION
Type:
Air
[
];
Water
[
];
Soil
[
];
Other
[
]
Light
source:
Sunlight
[
];
Xenon
lamp
[
];
Other
[
]
Light
spectrum:
<
text>
nm
Relative
intensity:
<
text>
(
based
on
intensity
of
sunlight)
Spectrum
of
substance:
[
e.
g.
lambda
(
max.)
(>
295
nm)
and
epsilon
(
max.)
or
epsilon
(
295nm)]
<
text>
nm
Concentration
of
substance:
<
text>
Temperature:
°
C
Direct
photolysis:
Half
life:
<
text>
Degradation:
<
text>
%
(
weight/
weight)
after
<
text>
(
exposure
time)
Quantum
yield:
<
text>
Indirect
photolysis:
Type
of
sensitizer:
<
text>
Concentration
of
sensitizer:
<
text>
Rate
constant
(
radical):
<
text>
cm3/
molecule*
sec
Degradation:
<
text>
Method:
calculated
[
];
measured
[
]
[
e.
g.
OECD,
other(
with
the
year
of
publication
or
updating
of
the
method
used)]
GLP:
Yes
[
]
No
[
]
?[
]
Test
substance:
>
text>,
purity:
<
text>
Remarks:
<
text>
References:
<
text>
24
Urea
(
CAS
#
57­
13­
6)
*
3.1.2
STABILITY
IN
WATER
Type:
Abiotic
(
hydrolysis)
[
X];
biotic
(
sediment)
[
]
Half
life:
>
1
yr
at
pH
<
text>
at
<
text>
°
C
<
text>
at
pH
<
text>
at
<
text>
°
C
after
<
text>
(
exposure
time)
Method:
PCHYDRO­
model
estimation
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
(
e.
g.
CAS
number,
name
and
percentage
of
degradation
products)
Extremely
slow
References:
National
Board
of
Water
and
the
Environment,
Finland.
1994.
Unpublished.

3.1.3
STABILITY
IN
SOIL
Type:
Field
trial
[
];
Laboratory
[
];
Other
[
]
Radiolabel:
Yes
[
]
No
[
]
?
[
]
Concentration:
<
text>
Soil
temperature:
<
text>
°
C
Soil
humidity:
<
text>
Soil
classification:
DIN
19863
[
];
NF
X31­
107
[
];
USDA
[
];
Other
[
]
Year:
<
text>
Contents
of
clay
etc.:
Clay
<
text>
%,
Silt
<
text>
%,
Sand
<
text>
%
Organic
carbon:
<
text>
Soil
pH:
<
text>
Cation
exchange
capacity:
<
text>
Microbial
biomass:
<
text>
Dissipation
time:
DT
50:
<
text>
DT
90:
<
text>
Dissipation:
<
text>
%
after
<
text>
(
time)
Method:
[
e.
g.
OECD,
others
(
with
the
year
of
publication
or
updating
of
the
method
used)]
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
<
text>
References:
<
text>

*
3.2
MONITORING
DATA
(
ENVIRONMENTAL)
Note
that
data
on
biological
effects
monitoring,
including
biomagnification,
and
biotransformation
and
kinetics
in
environmental
species
are
to
be
reported
in
section
4.7
and
4.8
respectively.
Nonetheless,
concentration
in
various
biota
should
be
reported
here.
Data
on
concentration
in
the
workplace
or
indoor
environment
should
be
reported
under
5.11.

Type
of
measurement:
Background
[
];
At
contaminated
site
[
];
Other
[
]
25
Urea
(
CAS
#
57­
13­
6)
Media:
<
text>
Results:
<
text>
Remarks:
<
text>
References:
<
text>

3.3
TRANSPORT
AND
DISTRIBUTION
BETWEEN
ENVIRONMENTAL
COMPARTMENTS
INCLUDING
ESTIMATED
ENVIRONMENTAL
CONCENTRATIONS
AND
DISTRIBUTION
PATHWAYS
(
e.
g.
during
the
chemical
life­
cycle.
The
information
should
indicate
whether
the
calculation
is
on
a
global
basis
or
is
site­
specific,
and
whether
it
is
based
on
laboratory
measurements
or
field
observations.)

*
3.3.1
TRANSPORT
Type
of
measurement:
Adsorption
[
];
Desorption
[
];
Volatility
[
];
Other
[
]
Media:
<
text>
Method:
<
text>
Results:
<
text>
Remarks:
<
text>
References:
<
text>

*
3.3.2
THEORETICAL
DISTRIBUTION
(
FUGACITY
CALCULATION)

Media:
air­
biota
[
];
Air­
biota­
sediment­
soil­
water
[
];
Soilbiota
[
];
Water­
air
[
];
Water­
biota
[
];
Water­
soil
[
];
Other
[
]
Method:
Fugacity
level
I
[
];
Fugacity
level
II
[
];
Fugacity
level
III
[
];
Fugacity
level
IV
[
];
Other
(
calculation)
[
];
Other
(
measurement)
[
]
Results:
<
text>
Remarks:
<
text>
References:
<
text>

3.4
IDENTIFICATION
OF
MAIN
MODE
OF
DEGRADABILITY
IN
ACTUAL
USE
Results:
<
text>
Remarks:
<
text>
References:
<
text>

*
3.5
BIODEGRADATION
Type:
Aerobic
[
X];
Anaerobic
[
]
Inoculum:
Adapted
[
X];
Non­
adapted
[
];
from
sewage
treatment
activated
sludge
26
Urea
(
CAS
#
57­
13­
6)
Concentration
of
the
chemical:
400
mg/
L
related
to
COD
[
];
DOC
[
];
Text
substance
[
X]
Medium:
Water
[
];
Water­
sediment
[
];
Soil
[
];
Sewage
treatment
[
X]
Degradation:
(
percentage
reduction/
exposure
time)
3,52,60,85
and
96%
decomposed
after
3
hr.,
7,10,14,16
days,
respectively
Results:
(
see
OECD
guideline)
Readily
biodeg.
[
];
Inherently
biodeg.
[
X];
Under
test
condition
no
biodegradation
observed
[
];
Other
[
]
Kinetics:
(
e.
g.
Zahn­
Wellens­
Test)
<
text>
%
in
<
text>
(
time)
Method:
Inherent
Biodegradability:
OECD
Guideline
302
B
(
1981)
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea,
purity:
<
text>
Remarks:
[
in
case
of
poorly
soluble
chemicals,
treatment
given
(
nature,
concentration,
CAS
number,
name
and
percentage
of
degradation
products
etc.)]
Main
mode
of
degradations
is
enzymatic
mineralization
References:
BASF
AG,
Labor
Oekologie,
internal
study
(
Proj.
1/
91/
0452
(
10/
1).

3.6
BOD5,
COD
OR
RATIO
BOD5/
COD
BOD5
Method:
[
e.
g.
OECD,
other(
with
the
year
of
publication
or
updating
of
the
method
used)]
Concentration:
<
text>
related
to
COD
[
];
DOC
[
];
Test
substance
[
]
Value:
<
text>
mg
O2/
L
GLP:
Yes
[
]
No
[
]
?
[
]

COD
Method:
<
text>
Value:
<
text>
mg
O2/
L
GLP:
Yes
[
]
No
[
]
?
[
]

Ratio
BOD5/
COD:
<
text>
Remarks:
<
text>
References:
<
text>

3.7
BIOACCUMULATION
Species:
<
text>
Exposure
period:
<
text>
Temperature:
°
C
Concentration:
<
text>
27
Urea
(
CAS
#
57­
13­
6)
BCF:
<
text>
Elimination:
Yes
[
]
No
[
]
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
Type
of
test:
Calculated
[
];
Measured
[
]
Static
[
];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
Due
to
the
low
log
Pow
value,
urea
is
not
at
all
likely
to
undergo
bioaccumulation.
Urea
is
readily
excreted
from
the
body.
References:
<
text>

3.8
ADDITIONAL
REMARKS
A.
Sewage
treatment
(
Information
on
treatability
of
the
substance)

Type:
Semi
continuous
activated
sludge
(
SCAS)
Degradation:
93­
98%
mean
disappearance
of
urea
in
24­
hour
cycle
(
as
determined
by
colorimetric
analysis)
Results:
<
text>
Remarks:
<
text>
References:
EPA,
Doc
878211481.
1983.
Biodegradation
testing
of
Santomelt
9909
CR
and
Ucar
Runway
de­
icer
fluids,
Monsanto
Co.,
Analytical
Chemistry
Special
Study
71­
8.
Job
No.
14499006.

B.
Other
information
[
Information
that
will
help
to
focus
the
exposure
assessment
(
either
qualitative
or
quantitative)]

Results:
<
text>
Remarks:
<
text>
References:
<
text>

4.
ECOTOXICITY
*
4.1
ACUTE/
PROLONGED
TOXICITY
TO
FISH
(
a)
Type
of
test:
Static
[
X];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Barilius
barna
28
Urea
(
CAS
#
57­
13­
6)
Exposure
period:
96
hr.
Results:
LC50
(
96
hr):
>
9,100
mg/
l
NOEC
=
<
text>
mg/
L
LOEC
=
<
text>
mg/
L
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Dodriyal
A.
K.
and
Bahuguna
A.
K.
1988.
Himalayan
Chem.
Bull.
5,
pp.
15­
16.

(
b)
Type
of
test:
Static
[
X];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Leuciscus
idus
melanotus
Exposure
period:
48
hr
Results:
LC50
(
48h)
>
10,000
mg/
l
NOEC
=
<
text>
mg/
L
LOEC
=
<
text>
mg/
L
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
<
text>
References:
Juhnke,
I.,
Lüdemann,
D.
1978.
Ergebnisse
der
Untersushung
200
chemischen
Verbindungen
auf
akute
Fischtoxicität
mit
dem
Goldorfentest.
Zeitschrift
Wasser
Abwasserforschung
11,5.

(
c)
Type
of
test:
Static
[
];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Tilapia
mossambica
Exposure
period:
96
hr
Results:
LC50
(
96hr)
=
22,500
mg/
L
NOEC
=
<
text>
mg/
L
LOEC
=
<
text>
mg/
L
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
29
Urea
(
CAS
#
57­
13­
6)
Remarks:
No
mortality
(
NOEC)
at
20,000
mg/
L;
100%
mortality
at
25,000
mg/
L
References:
<
text>

(
d)
Type
of
test:
Static
[
];
Semi­
static
[
X];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Colisa
fasciatus
(
young
tropical
fresh
water
teleost)
Exposure
period:
96
hr.
Results:
LC50
(
96h)
=
5.0
mg/
L
LC50
(
48h)
=
8.0
mg/
L
LC50
(
24h)
=
9.0
mg/
L
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Not
specified.
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
Study
is
partly
inadequately
reported.
Results
differ
significantly
from
other
acute
toxicity
results.
Not
a
valid
study.
References:
Pandey,
K.
and
Shukla,
J.
P.
1983.
Acta
Hydrochim.
et.
Hydrobiol.
11,1.
pp.
145­
190.

4.2
ACUTE
TOXICITY
TO
AQUATIC
INVERTEBRATES
*
A.
Daphnia
Type
of
test:
Static
[
];
Semi­
static
[
];
flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Daphnia
magna
Exposure
period:
48
hrs.
Results:
EC50
(
24h)
>
10,000
mg/
l
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
DIN
38412
Teil
11
(
modified)
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Bringmann,
G.
und
Kuhn,
R.
Zeitschrift
für
Wasser,
und
Abwasser.
1982.
Forschung
15(
1)
pp.
1­
6.
30
Urea
(
CAS
#
57­
13­
6)
*
B.
Other
aquatic
organisms
(
a)
Type
of
test:
Static
[
X];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Aedes
aegypti
larvae
(
mosquito)
Exposure
period:
4
hr.
Results:
LC50
(
4
hr)
60,000
mg/
l
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
<
text>
References:
Kramer,
V.
C.,
Schnell,
D.
J.,
and
Nickerson,
K.
W.
1983.
Journal
of
Invertebrate
Pathology
42:
285­
287.

(
b)
Type
of
test:
Static
[
X];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Entosiphon
sulcatum
(
protozoa
flagellate)
Exposure
period:
72
hr
Results:
Toxicity
Threshold
(
TT)
(
72
hr):
29
mg/
l
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Cell
multiplication
inhibition
test
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
In
some
extent
urea
exhibited
selective
toxic
action
on
Entosiphon
sulcatum.
For
example
toxicity
threshold
for
chloroform
was
>
6560
mg/
l.
References:
Bringmann,
G.
and
Kühn,
R.
1980.
Water
Research
14,
pp.
231­
241.

(
c)
Type
of
test:
Static
[
X];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Helisoma
trivolvis
(
freshwater
snail)
Exposure
period:
24
hr
Results:
LC50
(
24
hr)
14,241
mg/
1
Helisoma
trivolvis
egg
LC50
(
24
hr)
18,255
mg/
1
Helisoma
trivolvis
juveniles
LC50
(
24
hr)
30,060
mg/
1
Helisoma
trivolvis
adults
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
31
Urea
(
CAS
#
57­
13­
6)
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Tchounwou,
P.
B.,
Englande,
A.
J.,
and
Malek,
E.
A.
1991.
Arch.
of
Environmental
Contamination
and
Toxicology
21
pp.
359­
364.

*
4.3
TOXICITY
TO
AQUATIC
PLANTS,
e.
g.
algae
Species:
Scenedesmus
quadrigauda
green
algae
Endpoint:
Biomass
[
];
Growth
rate
[
];
Other
[
X]
Exposure
period:
72
hr
Results:
Toxicity
threshold
(
TT)
(
192
hr):
>
10,000
mg/
l.
EC50
(
h)
=
<
text>
mg/
L
NOEC
=
<
text>
mg/
L
LOEC
=
<
text>
mg/
L
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Cell
multiplication
inhibition
test
Open­
system
[
];
Closed­
system
[
]
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Bringmann,
G.
und
Kühn,
R.
1978.
Vom
Waser
50.
pp.
45­
60.

4.4
TOXICITY
TO
BACTERIA
(
Single
species
test
and
tests
on
overall
processes
such
as
nitrification
or
soil
respiration
are
included
in
this
item.)

(
a)
Type:
Aquatic
[
];
Field
[
];
Soil
[
];
Other
[
]
Species:
Pseudomonas
putida
Exposure
period:
16
hr
Results:
Toxicity
Threshold
(
TT)
16
hr:
>
10,000
mg/
l
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Bringmann,
G.
and
Kühn,
R.
1980.
Water
Research
14,
pp.
231­
241.

(
b)
Type:
Aquatic
[
X];
Field
[
];
Soil
[
];
Other
[
]
32
Urea
(
CAS
#
57­
13­
6)
Species:
Microcystis
aeruginosa
(
blue­
green
algae)
Exposure
period:
192
hr
Results:
Toxicity
Threshold
(
TT)
192
hr:
47
mg/
l
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Cell
multiplication
inhibition
test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Bringmann,
G.
and
Kühn,
R.
1978.
Vom
Wasser
50,
pp.
45­
60.

(
c)
Type:
Aquatic
[
];
Field
[
];
Soil
[
];
Other
[
X]
Species:
Photobacterium
luminescence
Exposure
period:
5
minutes
Results:
EC50
(
5
min):
24,000
mg/
l
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Microtox
assay
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
Bulich,
A.
A.,
Greene,
M.
W.,
and
Isenberg,
D.
L.
Reliability
of
bacterial
luminescence
assay
for
determination
of
the
toxicity
of
pure
compounds
and
complex
effluents.
pp.
338­
347;
in
Branson
&
Dickson
(
eds.)
Aquatic
Toxicology
and
Hazard
Assessment:
4th
conference,
ASTM
STP
737;
Philadelphia.

4.5
CHRONIC
TOXICITY
TO
AQUATIC
ORGANISMS
4.5.1
CHRONIC
TOXICITY
TO
FISH
(
Effects
on
reproduction,
embryo/
larva,
etc.)

Type
of
test:
Static
[
];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
Talapia
mossambica
Endpoint:
Length
of
fish
[
];
Weight
of
fish
[
];
Reproduction
rate
[
];
Other
[
X]
feeding
and
growth
Exposure
period:
25
days
Results:
See
remarks
EC50
(
d)
=
<
text>
mg/
L
Not
reported
NOEC
=
<
text>
mg/
L
Not
reported
LOEC
=
<
text>
mg/
L
Not
reported
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
33
Urea
(
CAS
#
57­
13­
6)
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
purity:
<
text>
Remarks:
decrease
in
feeding
and
growth
rates
with
increasing
concentration
(
5,000­
10,000,
­
15,000­
20,000
mg/
L)
References:
Planichamy,
S.,
Wilram,
S.,
and
Arunachalam,
S.
1985.
Sublethal
effects
of
urea
on
food
intake,
growth
and
conversion
in
Tilapia
mossambica.
Environment
and
Ecology,
Vol.
3,
No.
2,
pp
157­
161.

(*)
4.5.2
CHRONIC
TOXICITY
TO
AQUATIC
INVERTEBRATES
(
e.
g.
Daphnia
reproduction.
The
need
to
conduct
tests
for
this
endpoint
will
depend
inter
alia
upon
possible
concern
for
long
term
effects.)

Type
of
test:
Static
[
];
Semi­
static
[
];
Flow­
through
[
];
Other
(
e.
g.
field
test)
[
]
Open­
system
[
];
Closed­
system
[
]
Species:
<
text>
Endpoint:
Mortality
[
];
Reproduction
rate
[
];
Other
[
]
Exposure
period:
<
text>
Results:
<
text>
EC50
(
d)
=
<
text>
mg/
L
NOEC
=
<
text>
mg/
L
LOEC
=
<
text>
mg/
L
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
<
text>
References:
<
text>

4.6
TOXICITY
TO
TERRESTRIAL
ORGANISMS
4.6.1
TOXICITY
TO
SOIL
DWELLING
ORGANISMS
Type
of
test:
Artificial
Soil
[
];
Filter
Paper
[
];
Other
[
X]
Sandy
loam
soil
Species:
Grassland
earthworms
(
Oligochaeta,
Lumbricidae)
Endpoint:
Mortality
[
];
Weight
[
];
Other
[
X]
Numbers
and
biomass
Exposure
period:
<
text>
Results:
LC50
(
at
7
and
14
days
for
earthworms)
34
Urea
(
CAS
#
57­
13­
6)
Application
of
nitrogenous
fertilizers
to
grassland
for
long
period
may
have
a
deletrious
effect
on
earthworms
in
the
absence
of
liming.
Analytical
monitoring:
Yes
[
];
No
[
];
?
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Sandy
loam
soil.
Organic
matter
6.2
 
6.7%.
Fertilizer
was
organic
coated
urea,
the
organic
coating
being
based
on
soybean­
oil
at
annual
rate
60,
120
and
180
kg
N/
ha.
Soil
was
treated
annually
for
20
years.
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
<
text>
References:
Wei­
Chun
Ma,
L.,
Brussaard,
L.,
and
DeRidder,
J.
A.
1990.
Agriculture
and
Environment
30,
pp.
71­
80.

4.6.2
TOXICITY
TO
TERRESTRIAL
PLANTS
Species:
Glycine
max
(
L.)
Merr,
soybean
Endpoint:
Emergence
[
];
Growth
[
];
Other
[
X]
Exposure
period:
7
days
Results:
Leaf­
tip
necrosis
observed
after
foliar
fertilization
of
soybeans
with
urea
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
Exposure
to
9
mg
urea/
leaf
GLP:
Yes
[
]
No
[
X]
?[
]
Test
substance:
Urea
Remarks:
It
was
concluded
in
this
study
that
necrosis
resulted
from
accumulation
of
toxic
amounts
of
urea
rather
than
from
formation
of
toxic
amounts
of
ammonia.
References:
Krogmeir,
J.
M.,
McCarthy,
G.
W.,
and
Bremner,
J.
M.
1989.
Proc.
Natl.
Acad.
Sci.
USA
Vol.
86.
pp.
8189­
8191.

4.6.3
TOXICITY
TO
OTHER
NON
MAMMALIAN
TERRESTRIAL
SPECIES
(
INCLUDING
AVIAN)

Species:
Pigeon
Endpoint:
Mortality
[
];
Reproduction
rate
[
];
Weight
[
];
Other
[
]
Exposure
period:
<
text>
Results:
LDLO:
16,000
mg/
kg
subcutaneous
LD50
(
acute),
LC50
(
subacute)
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updated
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
35
Urea
(
CAS
#
57­
13­
6)
Remarks:
<
text>
References:
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.

4.7
BIOLOGICAL
EFFECTS
MONITORING
(
INCLUDING
BIOMAGNIFICATION)
[
Studies
on
variation
of
predominant
species
in
certain
ecosystems
(
e.
g.
mesocosm)
and
monitoring
of
biological
effects
are
included.]

Results:
Substance:
Nitrogenous
fertilizers
Species
or
ecosystem
studied:
Soil
properties
after
long
term
fertilization
with
urea
Effects
monitored:
Soil
pH
and
micronutrients
availabilities
Results:
20
years
of
urea
fertilization
reduced
soil
pH
significantly,
compared
with
the
control
area.
The
soil
acidification
occurs
due
to
nitrification
NH4+
which
is
decomposition
product
of
urea.
Urea
fertilization
caused
also
an
increase
in
micronutrients
(
Fe,
Cu,
Mn)
and
a
decrease
in
available
P
and
exchangeable
bases
(
Ca,
Mg,
Na).
Chemical
analysis:
mg/
kg
Fe
Cu
Mn
Ca
Mg
Na
metres
0.06­
0.1
urea
75.7
2.12
51.2
2566
478
15
no
urea
52.8
1.63
14.8
2949
548
25
metres
0.21­
0.29
urea
45.4
1.99
15.6
3666
719
42
no
urea
44.7
1.94
8.9
3893
822
71
Remarks:
[
Information
on
environmental
conditions
(
e.
g.
water
characteristics;
suspended
matter,
pH,
temperature,
hardness;
soil/
sediment
characteristics:
%
organic
matter,
clay
content.]
Soil
acidification
occurred
also
on
areas
treated
with
ammonia,
NH4NO3
and
urea­
NH4NO3
mixture.
The
annual
rate
of
N/
ha
was
105
­
224
kg
and
corn
(
Zea
mays
L.),
grain
sorghum
(
Sorghum
bicolor),
winter
wheat
(
Triticum
aestivum
L.)
and
soybean
(
Glycine
max
L.)
were
planted.
References:
Darusman,
L.
R.,
et
al.
1991.
Soil
Sci.
Soc.
Am.
J.
55:
pp.
1097­
1100.

4.8
BIOTRANSFORMATION
AND
KINETICS
(
Under
this
item,
studies
on
absorption,
distribution,
metabolism
and
excretion
etc.
should
be
given.)
36
Urea
(
CAS
#
57­
13­
6)
Type:
Animal
[
];
Aquatic
[
];
Plant
[
];
Terrestrial
[
];
Other
[
]
Results:
<
text>
Remarks:
Ammonia
is
toxic
to
all
vertebrates.
It
can
be
converted
to
the
less
toxic
urea,
but
this
is
a
metabolically
expensive
process
found
only
in
terrestrial
vertebrates
that
cannot
readily
excrete
ammonia
and
marine
fish
that
use
urea
as
osmotic
filler.
Freshwater
fish
mostly
excrete
ammonia
with
only
a
small
quantity
of
urea.
Urea
is
the
end
product
of
biochemical
protein
decomposition
and
the
main
component
of
mammalian
urine.
References:
Randall,
D.
J.,
Wood,
C.
M.,
Perry,
S.
F.,
Bergman,
H.,
Maloiy,
G.
M.
O.,
Mommsen,
T.
P.,
and
Wright,
P.
A.
1989.
Urea
excretion
as
a
strategy
for
survival
in
a
fish
living
in
a
very
alkaline
environment.
Nature
337
(
12)
pp.
165­
166.
Harper,
H.
A.
and
Rodwell,
V.
W.
1977.
Review
of
Physiological
Chemistry,
16th
ed.,
Lange
Medical
Publications,
Los
Altos
California.
p.
625.

4.9
ADDITIONAL
REMARKS
Results:
<
text>
Remarks:
<
text>
References:
<
text>

5.
TOXICITY
(
Where
observations
on
humans
are
available,
these
should
be
entered
in
the
appropriate
"
comments"
section
or
under
section
5.11.)

*
5.1
ACUTE
TOXICITY
5.1.1
ACUTE
ORAL
TOXICITY
(
a)
Type:
LD0
[
];
LD100
[
];
LD50
[
];
LDL0
[
];
Other
[
]
Species/
strain:
Rat/
strain
not
mentioned
Mouse/
strain
not
mentioned
Value:
LD50
or
other
measure
of
acute
toxicity
(
e.
g.,
in
case
fixed
dose
test):
1.
LD50:
14,300
mg/
kg
orl­
rat­
male
2.
LD50:
15,000
mg/
kg
orl­
rat­
female
1.
LD50:
11,500
mg/
kg
orl­
mouse­
male
2.
LD50:
13,000
mg/
kg
orl­
mouse­
female
37
Urea
(
CAS
#
57­
13­
6)
Other
data:
LD50
values
to
mammals
in
non­
oral
exposure:
1.
LD50:
9,400
mg/
kg
scu­
rat­
male
1.
LD50:
8,200
mg/
kg
scu­
rat­
female
2.
LD50:
9,200
mg/
kg
scu­
mouse­
male
2.
LD50:
10,700
mg/
kg
scu­
mouse­
female
1.
LD50:
5,400
mg/
kg
ivn­
rat­
male
1.
LD50:
5,300
mg/
kg
ivn­
rat­
female
2.
LD50:
4,600
mg/
kg
ivn­
mouse­
male
2.
LD50:
5,200
mg/
kg
ivn­
mouse­
female
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Not
known
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
The
general
symptoms
consisting
mainly
of
sedation,
loss
of
righting
reflex
and
staggering
gait
were
noted
in
both
rats
and
mice.
References:
Sato,
N.
et
al.,
OY­
Yakari
(
Pharmacometrics
Tokyo)
13.
1978.
pp.
749­
772.

(
b)
Type:
LD0
[
];
LD100
[
];
LD50
[
];
LDL0
[
];
Other
[
]
Species/
strain:
1.
Cattle
(
cow)/
strain
not
mentioned
2.
Sheep/
strain
not
mentioned
3.
Pony/
strain
not
mentioned
4.
Rabbit/
strain
not
mentioned
5.
Dog/
strain
not
mentioned
6.
Frog/
strain
not
mentioned
7.
Pigeon/
strain
not
mentioned
8.
Guinea
pig/
strain
not
mentioned
Value:
LD50
or
other
measure
of
acute
toxicity
(
e.
g.,
in
case
fixed­
dose
test):
1.
LD50:
510mg/
kg
orl­
cattle
1.
LD50:
600­
1,080
mg/
kg
orl­
cattle
1.
LDLO:
116
mg/
kg
orl­
cattle
2.
LD50:
510
mg/
kg
orl­
sheep
2.
LDLO:
160
mg/
kg
orl­
sheep
3.
LDLO:
3,310­
3,610
mg/
kg
orl­
pony
4.
LDLO:
5,000
mg/
kg
orl­
rabbit
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Detailed
information
of
the
test
methods
was
not
available
at
time
of
the
evaluation.
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
References:
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.
38
Urea
(
CAS
#
57­
13­
6)
(
c)
Type:
LD0
[
];
LD100
[
];
LD50
[
];
LDL0
[
];
Other
[
]
Species/
strain:
Ruminants
Value:
LD50
or
other
measure
of
acute
toxicity
(
e.
g.,
in
case
fixed­
dose
test):
Urea
can
cause
clinical
signs
of
toxicosis
in
ruminants
at
300
­
500
mg/
kg
body
wt
and
death
at
1000
­
1500
mg/
kg
body
wt.
Horses
are
less
susceptible,
urea
being
lethal
at
approximately
4000
mg/
kg
body
wt.
Monogastric
animals,
such
as
swine
and
baby
calves,
are
not
affected
by
urea
or
biuret
except
for
a
mild
diuretic
action.
Discriminating
dose:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Not
specified
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
References:
Oehme,
F.
W.
and
Barrel,
D.
S.
1986.
Veterinary
Gastrointestinal
Toxicology,
Chapter
17;
in
Rozman
K.
and
Hänninen
O.
(
eds.).
Gastrointestinal
Toxicology,
Elsevier
Science
Publishers,
Amsterdam.
pp.
489­
490.

(
d)
Type:
LD
0
[
];
LD100
[
];
LD50
[
];
LDL0
[
];
Other
[
]
Species/
strain:
Young
pigs
(
3)
Value:
LDLO:
>
16,000
mg/
kg
oral­
pig
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea,
purity:
<
text>
Remarks:
Ten
percent
(
m/
m)
urea
in
pig
food
over
a
period
of
5
days
was
without
apparent
deleterious
effects.
References:
Button,
J.
P.
et
al.
1982.
Journal
of
the
South
African
Veterinary
Association,
53
No.
1,
pp.
67­
68.

5.1.2
ACUTE
INHALATION
TOXICITY
Type:
LC0
[
];
LC100
[
];
LC50
[
];
LCL0
[
];
Other
[
]
Species/
strain:
Not
specified
Exposure
period:
<
text>
Value:
22
mg/
m3
dermal
and
respiratory/
mucous
membrane
­
mild
irritation
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
dust
Remarks:
<
text>
39
Urea
(
CAS
#
57­
13­
6)
References:
National
Safety
Council.
UREA:
Safe
Use
and
Handling.
Data
Sheet
1­
691,
Rev.
90.

5.1.3
ACUTE
DERMAL
TOXICITY
Type:
LD0
[
];
LD100
[
];
LD50
[
];
LDL0
[
];
Other
[
]
Species/
strain:
<
text>
Value:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
<
text>
References:
<
text>

5.1.4
ACUTE
TOXICITY
BY
OTHER
ROUTES
OF
ADMINISTRATION
(
e.
g.
subcutaneous,
intravenous,
etc.)

Type:
LC0
[
];
LC100
[
];
LC50
[
];
LCL0
[
];
LD0
[
];
LD100
[
];
LD50
[
];
LDL0
[
];
Other
[
]
Species/
strain:
<
text>
Route
of
Administration:
i.
m.
[
];
i.
p.
[
];
i.
v.
[
];
Infusion
[
];
s.
c.
[
];
Other
[
]
Exposure
period:
<
text>
Value:
<
text>
mg/
kg
b.
w.
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
<
text>
References:
<
text>

5.2
CORROSIVENESS/
IRRITATION
5.2.1
SKIN
IRRITATION/
CORROSION
(
a)
Species/
strain:
Human
skin
Results:
Highly
corrosive
[
];
Corrosive
[
];
Highly
irritating
[
];
Irritating
[
];
Moderately
irritating
[
];
Slightly
irritating
[
];
Not
irritating
[
]
Test
results:
give
maximum
scores
after
72
hrs.
for
scarified
human
skin:
7.5%
urea
(
in
water)
 
slight
irritancy
30%
urea
(
in
water)
 
marked
irritancy
40
Urea
(
CAS
#
57­
13­
6)
Aquacare
HP­
10%
urea
 
slight
irritancy
Classification:
(
if
possible,
according
to
EC
Directive
67/
548/
EEC)
Highly
corrosive
(
causes
severe
burns)
[
];
Corrosive
(
causes
burns)
[
];
Irritating
[
];
Not
irritating
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Chamber­
Scarification
Test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea;
7.5%,
30%
solutions
in
water
Aquacare
HP
­
10%
urea
(
Allergan)
Remarks:
Other
data:
Comparison
between
hypo­
and
hyperreactive
individuals
with
30%
urea
in
water
after
48
hrs:
Individual
type
Scarified
skin
Normal
Skin
Hyporeactors
0.8
=
slight
0
=
no
irritancy
Hyperreactors
2.4
=
moderate
0
=
no
irritancy
References:
Frosch,
P.
J.
and
Kligman,
A.
M.
1977.
The
Chamber­
Scarification
Test
for
Assessing
Irritancy
to
Topically
Applied
Substances;
in
Drill,
V.
A.
and
Lazar,
P.,
(
eds.)
Cutaneous
Toxicity,
Academic
Press
Inc.,
New
York.
pp.
127­
153.

(
b)
Species/
strain:
Human
skin
Results:
Highly
corrosive
[
];
Corrosive
[
];
Highly
irritating
[
];
Irritating
[
];
Moderately
irritating
[
];
Slightly
irritating
[
];
Not
irritating
[
X]
Classification:
(
if
possible,
according
to
EC
Directive
67/
548/
EEC)
Highly
corrosive
(
causes
severe
burns)
[
];
Corrosive
(
causes
burns)
[
];
Irritating
[
];
Not
irritating
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Not
specified
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
10%
water
solution
Remarks:
24
hour
exposure
References:
Alchangian,
L.
V.,
et
at.
1986.
Vestn.
Dermatol.
Venerol.
9,
pp.
26­
29.

(
c)
Species/
strain:
Male
nude
mouse/
MF1
h
Results:
Highly
corrosive
[
];
Corrosive
[
];
Highly
irritating
[
];
Irritating
[
];
Moderately
irritating
[
];
Slightly
irritating
[
];
Not
irritating
[
X]
Classification:
(
if
possible,
according
to
EC
Directive
67/
548/
EEC)
Highly
corrosive
(
causes
severe
burns)
[
];
Corrosive
(
causes
burns)
[
];
Irritating
[
];
Not
irritating
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Others
GLP:
Yes
[
]
No
[
]
?
[
X]
41
Urea
(
CAS
#
57­
13­
6)
Test
substance:
Urea,
10%
water
solution
Remarks:
10%
urea
induced
no
discernible
change
in
the
histological
appearance
of
the
skin.
References:
Lashmar,
U.
T.,
et
al.
1989.
J.
Pharm.
Pharmacol.
41:
118­
121.

(
d)
Species/
strain:
Rabbit/
strain
not
mentioned
Results:
Highly
corrosive
[
];
Corrosive
[
];
Highly
irritating
[
];
Irritating
[
];
Moderately
irritating
[
];
Slightly
irritating
[
];
Not
irritating
[
X]
Classification:
(
if
possible,
according
to
EC
Directive
67/
548/
EEC)
Highly
corrosive
(
causes
severe
burns)
[
];
Corrosive
(
causes
burns)
[
];
Irritating
[
];
Not
irritating
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
20
hrs.
semiocclusive
application
of
50%
urea
water
solution
on
the
back
and
ear
skin
of
rabbit.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
50%
water
solution
Remarks:
The
original
report
of
the
study
was
not
available
for
the
Finnish
expert
group
at
the
time
of
the
evaluation.
References:
BASF
AG,
Abteilung
Toxikologie,
internal
study
(
I/
140),
unpublished;
as
cited
in
BASF
AG,
AIDA.

5.2.2
EYE
IRRITATION/
CORROSION
Species/
strain:
Rabbit/
strain
not
mentioned
Results:
Highly
corrosive
[
];
Corrosive
[
];
Highly
irritating
[
];
Irritating
[
];
Moderately
irritating
[
];
Slightly
irritating
[
];
Not
irritating
[
X]
Classification:
(
if
possible,
according
to
EC
Directive
67/
548/
EEC)
Irritating
[
];
Not
irritating
[
];
Risk
of
serious
damage
to
eyes
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
OECD
405
GLP:
Yes
[
X]
No
[
]
?
[
]
Test
substance:
Urea
Remarks:
The
original
report
of
the
study
was
not
available
for
the
Finnish
scientific
expert
group
at
the
time
of
the
evaluation.
References:
BASF
AG,
Abteilung
Toxikologie,
internal
study
(
88/
207),
unpublished;
as
cited
in
BASF
AG,
AIDA.

5.3
SKIN
SENSITIZATION
Type:
<
text>
Species/
strain:
Human
skin
42
Urea
(
CAS
#
57­
13­
6)
Results:
Sensitizing
[
];
Not
sensitizing
[
X];
Ambiguous
[
]
Classification:
(
if
possible,
according
to
EC
Directive
67/
548/
EEC)
Sensitizing
[
];
Not
sensitizing
[
X]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Not
specified
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
10%
water
solution
Remarks:
<
text>
References:
Alchangian,
L.
V.,
et
al.
1986.
Vestn.
Dermatol.
Venerol
9:
26­
29.

*
5.4
REPEATED
DOSE
TOXICITY
(
a)
Species/
strain:
Rat/
Wistar
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
X]
Route
of
Administration:
Dermal
Exposure
period:
4
weeks
Frequency
of
treatment:
<
text>
Post
exposure
observation
period:
<
text>
Dose:
10%,
20%
and
40%
in
ointment
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL:
<
text>
LOEL:
<
text>
Results:
No
dose­
dependent
toxicity
was
observed.
There
were
no
consistent
treatment­
related
effects
on
standard
haematological
parameters,
clinical
chemistry,
organ
weights
or
organ
histopathology,
including
the
testicles,
prostate,
seminal
vesicles,
ovaries
and
the
uterus.
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Substance
was
applied
to
the
back
skin
(
20
cm2)
during
4
weeks.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
References:
Sato,
N.
et
al.
1977.
Toxicological
studies
of
urea.
Acute,
subacute
and
chronic
test
in
rats
and
mice.
Oyo­
Yakuri
(
Pharmacometrics
Tokyo)
13:
749­
772.

(
b)
Species/
strain:
Rat/
Wistar
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
X]
Route
of
Administration:
Dermal
Exposure
period:
24
weeks
Frequency
of
treatment:
<
text>
Post
exposure
observation
period:
<
text>
43
Urea
(
CAS
#
57­
13­
6)
Dose:
10%,
20%
and
40%
in
ointment
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL:
<
text>
LOEL:
<
text>
Results:
There
were
no
consistent
treatment­
related
effects
on
standard
haematological
parameters,
clinical
chemistry
or
different
organs.
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
The
substance
was
applied
to
the
back
skin
(
20
cm)
during
24
weeks.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
References:
Sato,
N.
et
al.
1977.
Toxicological
studies
of
urea.
Acute,
subacute
and
chronic
test
in
rats
and
mice.
Oyo­
Yakuri
(
Pharmacometrics
Tokyo)
13:
749­
772.

(
c)
Species/
strain:
Rat/
not
known
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
X]
Route
of
Administration:
Oral
Exposure
period:
190
days
Frequency
of
treatment:
<
text>
Post
exposure
observation
period:
<
text>
Dose:
2000­
25,000
mg/
kg/
day
in
fodder
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL:
<
text>
LOEL:
<
text>
Results:
250,000
ppm
and
200,000
ppm
were
lethal
in
12
days
and
20­
76
days,
respectively.
There
was
weight
loss
and
suppression
of
sexual
function
at
lower
doses.
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Repeated
dosing
for
190
days,
20,000­
250,000
ppm
(
about
2000­
25000
mg/
kg/
day)
in
fodder.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
purity
not
known
Remarks:
The
validity
of
the
study
is
limited
by
the
small
number
of
animals
used
(
often
1
to
3
per
group)
and
failure
to
report
actual
food
intake.
Extreme
weight
loss
of
the
rats
suggests
that
inanition
was
likely.
References:
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.

(
d)
Species/
strain:
Dog/
not
known
44
Urea
(
CAS
#
57­
13­
6)
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
X]
Route
of
Administration:
Subcutaneous
Exposure
period:
45
days
Frequency
of
treatment:
Every
8
hours
Post
exposure
observation
period:
<
text>
Dose:
3,000
to
4,000
mg/
kg
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL:
<
text>
LOEL:
<
text>
Results:
Plasma
urea
levels
were
200
to
700
mg/
100
ml.
The
treatment
caused
mild
drowsiness
and
increased
diuresis
in
animals
but
did
not
affect
hematocrit,
platelet
counts
nor
EEG.
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Urea
was
injected
subcutaneously
every
8
hours
into
12
unilaterally
nephrectomized
dogs
for
45
days.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
<
text>
References:
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.

*
5.5
GENETIC
TOXICITY
IN
VITRO
A.
Bacterial
Test
(
a)
Type:
(
e.
g.
Bacterial
reverse
mutation
assay,
Bacterial
gene
mutation
study,
Cytogenetic
Assay
etc.)
Bacterial
gene
mutation
study
System
of
testing:
Ames
assay
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
];
With
and
Without
[
X];
No
Data
[
]
Results:
Cytotoxicity
conc:
<
text>
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
X]
Without
metabolic
activation:
[
]
[
]
[
X]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Ames
test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
purity
unknown
Remarks:
<
text>
45
Urea
(
CAS
#
57­
13­
6)
References:
Ishidate,
M.,
Sofuni,
T.,
and
Yoshikawa,
K.
1981.
Chromosomal
aberration
tests
in
vitro
as
a
primary
screening
tool
for
environmental
mutagens
and/
or
carcinogens.
GANN
Monograph
on
Cancer
Research
27:
95­
108.

(
b)
Type:
(
e.
g.
Bacterial
reverse
mutation
assay,
Bacterial
gene
mutation
study,
Cytogenetic
Assay
etc.)
Bacterial
gene
mutation
study
System
of
testing:
Ames
assay
Concentration:
5­
5,000
 g/
plate
Metabolic
activation:
With
[
];
Without
[
];
With
and
Without
[
X];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
X]
Without
metabolic
activation:
[
]
[
]
[
X]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Ames
test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
99%
pure,
dissolved
in
water
Remarks:
Negative
results
at
a
dose
range
of
5­
5000
µ
g/
plate.
References:
Shimizu,
H.,
Suzuki,
Y.,
Takemura,
N.,
Goto,
S.,
and
Matsushita,
H.
1985.
The
results
of
microbial
mutation
test
for
forty­
three
industrial
chemicals.
Jpn.
J.
Ind.
Health
27:
400­
419.

(
c)
Type:
(
e.
g.
Bacterial
reverse
mutation
assay,
Bacterial
gene
mutation
study,
Cytogenetic
Assay
etc.)
Bacterial
gene
mutation
study
System
of
testing:
Ames
assay
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
];
With
and
Without
[
X];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
X]
Without
metabolic
activation:
[
]
[
]
[
X]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Ames
test
GLP:
Yes
[
]
No
[
]
?
[
X]
46
Urea
(
CAS
#
57­
13­
6)
Test
substance:
Urea,
99%
pure,
dissolved
in
DMSO
Remarks:
Negative
results
at
a
dose
range
of
100­
10000
ug/
plate
with
and
without
metabolic
activation
with
rat
liver
and
hamster
liver
S9
mix.
References:
Mortelmans,
K.,
Haworth,
S.,
Lawler,
T.,
Speck,
W.,
Tainer,
B.,
and
Zeiger,
E.
1986.
Salmonella
mutagenicity
tests:
II.
Results
from
the
testing
of
270
chemicals.
Env.
Mutag.
8,
Suppl.
7,
pp.
1­
119.

B.
Non­
bacterial
in
vitro
test
(
a)
Type:
(
e.
g.
mammalian
cell
gene
mutation
assay,
cytogenetic
assay
etc.)
Cytogenetic
Assay
System
of
testing:
Chinese
hamster
fibroblast
(
CHL)
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
X];
With
and
Without
[
];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
]
Without
metabolic
activation:
[
X]
[
]
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Chromosomal
aberration
test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
purity
unknown,
dissolved
in
physiological
saline
Remarks:
Aberrations
in
37%
of
metaphases
at
24
h
(
chromosomal
gaps,
chromatid
or
chromosomal
breaks,
translocations,
fragmentation).
The
maximally
effective
concentration
was
266
mM,
a
very
high
concentration
suggesting
a
low
clastogenic
potential.
References:
Ishidate,
M.
and
Odashima,
S.
1977.
Chromosome
test
with
134
compounds
on
Chinese
hamster
cells
in
vitro
­
a
screening
for
chemical
carcinogens.
Mut.
Res.
48:
337­
354.

(
b)
Type:
(
e.
g.
mammalian
cell
gene
mutation
assay,
cytogenetic
assay
etc.)
Cytogenetic
Assay
System
of
testing:
Chinese
hamster
fibroblast
(
CHL)
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
X];
With
and
Without
[
];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
47
Urea
(
CAS
#
57­
13­
6)
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
]
Without
metabolic
activation:
[
X]
[
]
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Chromosomal
aberration
test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
purity
unknown
Remarks:
Chromosomal
aberrations
detected
in
20%
of
metaphases
at
urea
concentration
of
13
g/
l
(
216
mM),
indicating
a
low
clastogenic
potential.
References:
Ishidate,
M.,
Sofuni,
T.,
and
Yoshikawa,
K.
1981.
Chromosomal
aberration
tests
in
vitro
as
a
primary
screening
tool
for
environmental
mutagens
and/
or
carcinogens.
GANN
Monograph
on
Cancer
Research.
27:
95­
108.

(
c)
Type:
(
e.
g.
mammalian
cell
gene
mutation
assay,
cytogenetic
assay
etc.)
Mammalian
cell
gene
mutation
assay
System
of
testing:
Mouse
lymphoma
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
X];
With
and
Without
[
];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
]
Without
metabolic
activation:
[
X]
[
]
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Mouse
lymphoma
TK
locus
assay
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
laboratory
grade
Remarks:
Weakly
positive
at
very
high
urea
concentrations
530­
662
mM,
negative
at
132
mM,
equivocal
at
265­
397
mM.
Authors
discuss
the
possibility
that
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.
References:
Wangenheim,
J.
and
Bolcsfoldi,
G.
1988.
Mouse
lymphoma
L5178Y
thymidine
kinase
locus
assay
of
50
compounds.
Mutagenesis
3:
193­
205.
48
Urea
(
CAS
#
57­
13­
6)
(
d)
Type:
(
e.
g.
mammalian
cell
gene
mutation
assay,
cytogenetic
assay
etc.)
Cytogenetic
Assay
System
of
testing:
Rat
hepatocytes
Concentration:
<
text>
Metabolic
activation:
With
[
X];
Without
[
];
With
and
Without
[
];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
X]
Without
metabolic
activation:
[
]
[
]
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Analysis
for
DNA
singlestrand
breaks
by
alkaline
elution.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
laboratory
grade,
dissolved
in
water
Remarks:
Negative
(
0.3­
3mM)
References:
Sina,
J.
F.,
Bean,
C.
L.,
et
al.
1984.
Evaluation
of
the
alkaline
elution/
rat
hepatocyte
assay
as
a
predictor
of
carcinogenic/
mutagenic
potential.
Mut.
Res.
1132:
357­
391.

(
e)
Type:
(
e.
g.
mammalian
cell
gene
mutation
assay,
cytogenetic
assay
etc.)
Mammalian
cell
gene
mutation
assay
System
of
testing:
Mouse
lymphoma
L5178Y/
TK+/­
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
X];
With
and
Without
[
];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
]
Without
metabolic
activation:
[
X]
[
]
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Analysis
for
DNA
signlestrand
breaks
by
unwinding
and
hydroxyapatite
elution
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
laboratory
grade
Remarks:
Positive
at
very
high
concentrations
628
and
718
mM
with
relative
fractions
of
ssDNA
of
9.2
and
17.3%,
respectively.
Although
a
dose­
response
was
found,
49
Urea
(
CAS
#
57­
13­
6)
lower
urea
concentrations
(
359­
539
mM)
did
not
yield
responses
classified
as
positive.
References:
Garberg,
P.,
Åkerblom,
E­
L.,
and
Bolcsfoldi,
G.
1988.
Evaluation
of
genotoxicity
test
measuring
DNA­
strand
breaks
in
mouse
lymphoma
cells
by
alkaline
unwinding
and
hydroxyapatite
elution.
Mut.
Res.
203:
155­
176.

*
5.6
GENETIC
TOXICITY
IN
VIVO
(
a)
Type:
(
e.
g.
mammalian
cell
gene
mutation
assay,
cytogenetic
assay
etc.)
Cytogenetic
Assay
System
of
testing:
Mouse/
Swiss
albino
Concentration:
<
text>
Metabolic
activation:
With
[
];
Without
[
];
With
and
Without
[
];
No
Data
[
]
Results:
Cytotoxicity
conc:
With
metabolic
activation:
<
text>
Without
metabolic
activation:
<
text>
Precipitation
conc:
<
text>
Genotoxic
effects:
+
?
­
With
metabolic
activation:
[
]
[
]
[
]
Without
metabolic
activation:
[
X]
[
]
[
]
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Bone
marrow
cytogenetic
test
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea,
purity
unknown
Remarks:
Bone
marrow
cell
metaphases
from
mice
fed
with
urea
500
mg
per
animal
per
day
in
food
for
5
days
(
dosage
approaching
an
acutely
lethal
dose)
exhibited
chromosome
breaks,
acentric
fragments,
translocations,
gaps
and
constrictions
at
a
7­
fold
rate
compared
to
controls.
The
interpretation
of
this
clastogenic
effect
is
limited
by
the
usage
of
a
single
extremely
high
dose
level.
References:
Chaurasia,
O.
P.
and
Sinna,
S.
P.
1987.
Effects
of
urea
on
mitotic
chromosomes
of
mice
and
onion.
Cytologia
52:
877­
882.

5.7
CARCINOGENICITY
(
a)
Species/
strain:
Mouse/
C57B1/
6
Sex:
Female
[
];
Male
[
];
Male/
Female
[
X];
No
Data
[
]
Route
of
Administration:
diet
Exposure
period:
>
12
months
50
Urea
(
CAS
#
57­
13­
6)
Frequency
of
treatment:
<
text>
Post
exposure
observation
period:
4
months
Doses:
0.45%,
0.9%,
4.5%
in
diet
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
Results:
Not
carcinogenic
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Chronic
toxicity
and
carcinogenicity
screening
study
over
12
months
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
Five
animals
per
sex
from
all
dose
groups
were
necropsied
at
the
end
of
the
treatment
period,
and
the
gonads
were
histologically
examined.
No
pathology
was
reported.
After
further
4
months
of
follow
up,
all
survivors
were
killed,
necropsied
and
the
tissues
were
fixed.
However,
concerning
the
reproductive
organs
histological
tumor
data
on
the
ovary
and
the
uterus
only
were
given.
Other
sex
organs
may
not
have
been
histologically
studied.
References:
Fleischman,
R.
W.,
et
al.
1980.
J.
Environmental
Pathology
&
Toxicology
3,
(
5/
6),
pp.
149­
170.

(
b)
Species/
strain:
Rat/
Fischer
344
Sex:
Female
[
];
Male
[
];
Male/
Female
[
X];
No
Data
[
]
Route
of
Administration:
Diet
Exposure
period:
>
12
months
Frequency
of
treatment:
<
text>
Post
exposure
observation
period:
4
months
Doses:
0.45%,
0.9%,
4.5%
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
Results:
Not
carcinogenic
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Chronic
toxicity
and
carcinogenicity
screening
study
over
12
months
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
Five
animals
per
sex
from
all
dose
groups
were
necropsied
at
the
end
of
the
treatment
period,
and
the
gonads
were
histologically
examined.
No
pathology
was
reported.
After
further
4
months
of
follow
up
all
survivors
were
killed,
necropsied
and
the
tissues
were
fixed.
The
testes,
prostate
and
uterus
were
histologically
examined
for
the
occurrence
of
tumors.
Although
there
was
a
statistically
increased
incidence
of
interstitial
cell
51
Urea
(
CAS
#
57­
13­
6)
adenomas
of
the
testis
in
the
high
dose
group,
its
biological
significance
was
deemed
questionable,
since
the
lesion
may
occur
in
100%
of
controls.
References:
Fleischman,
R.
W.,
et
al.
1980.
J.
Environmental
Pathology
&
Toxicology
3,
(
5/
6),
pp.
149­
170.

5.8
TOXICITY
TO
REPRODUCTION
Type:
Fertility
[
];
One­
generation
study
[
];
Two­
generation
study
[
];
Other
[
X]
Species/
strain:
<
text>
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
]
Route
of
Administration:
<
text>
Exposure
period:
<
text>
Frequency
of
treatment:
<
text>
Post
exposure
observation
period:
<
text>
Duration
of
the
test
<
text>
Doses:
<
text>
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL
Parental:
<
text>
NOEL
F1
Offspring:
<
text>
NOEL
F2
Offspring:
<
text>
Results:
<
text>
General
parental
toxicity:
<
text>
Toxicity
to
offspring:
(
weights
of
litter,
postnatal
growth,
viability,
etc.)
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
<
text>
GLP:
Yes
[
]
No
[
]
?
[
]
Test
substance:
<
text>,
purity:
<
text>
Remarks:
Based
on
the
carcinogenicity
screening
studies
with
mice
and
rats
and
repeated
dose
toxicity
studies
by
dermal
route
with
rats,
where
no
toxic
effects
were
observed
in
the
gonads,
even
after
histopathological
examination,
and
the
lack
of
evidence
for
developmental
toxicity
in
limited
mouse
and
rat
studies,
urea
would
not
be
expected
to
display
significant
potential
for
reproductive
toxicity.
References:
<
text>

*
5.9
DEVELOPMENTAL
TOXICITY/
TERATOGENICITY
(
a)
Species/
strain:
Mouse/
ICR
52
Urea
(
CAS
#
57­
13­
6)
Sex:
Female
[
X];
Male
[
];
Male/
Female
[
];
No
Data
[
]
Route
of
Administration:
Oral
Duration
of
the
test:
<
text>
Exposure
period:
Single
dose
Frequency
of
treatment:
<
text>
Doses:
2,000
mg/
kg
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL
Maternal
Toxicity:
<
text>
NOEL
teratogenicity:
<
text>
Results:
Not
teratogenic
Maternal
general
toxicity:
not
toxic
Pregnancy/
litter
data:
<
text>
Fetal
data:
No
effects
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
A
single
oral
dose
study
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
A
single
dose,
2000
mg/
kg
was
administered
orally
to
10
pregnant
mice
on
day
10
of
pregnancy.
Not
an
adequate
teratogenicity
study.
References:
Teramoto,
et
al.
1981.
Teratology
23:
335­
342.

(
b)
Species/
strain:
Rat/
Wistar
Sex:
Female
[
X];
Male
[
];
Male/
Female
[
];
No
Data
[
]
Route
of
Administration:
Oral
Duration
of
the
test:
<
text>
Exposure
period:
Single
oral
dose
Frequency
of
treatment:
<
text>
Doses:
2,000
mg/
kg
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL
Maternal
Toxicity:
<
text>
NOEL
teratogenicity:
<
text>
Results:
Not
teratogenic
Maternal
general
toxicity:
Not
toxic
Pregnancy/
litter
data:
<
text>
Fetal
data:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
A
single
oral
dose
study
GLP:
Yes
[
]
No
[
X]
?
[
]
Test
substance:
Urea
Remarks:
A
single
dose,
2000
mg/
kg
was
administered
orally
only
to
4
pregnant
rats
on
day
12
of
pregnancy.
Not
an
adequate
teratogenicity
study.
References:
Teramoto,
et
al.
1981.
Teratology
23:
335­
342.
53
Urea
(
CAS
#
57­
13­
6)
(
c)
Species/
strain:
Rat/
Wistar
Sex:
Female
[
X];
Male
[
];
Male/
Female
[
];
No
Data
[
]
Route
of
Administration:
Gavage
Duration
of
the
test:
<
text>
Exposure
period:
14
days
Frequency
of
treatment:
2
dose,
12
hours
aparat
Doses:
50
g/
kg/
day
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL
Maternal
Toxicity:
<
text>
NOEL
teratogenicity:
<
text>
Results:
Blood
urea
levels
ranged
from
about
1000
mg/
100
ml
at
one
hour
after
administration
to
100
mg/
100
ml
before
the
next
dose
(
12
h
later).
No
hypertrophy
or
other
kidney
changes
were
detected
nor
were
any
teratogenic
effects
noted.
Maternal
general
toxicity:
<
text>
Pregnancy/
litter
data:
<
text>
Fetal
data:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Urea
in
water
was
given
in
2
doses
12
h
apart
by
gavage
to
6
rats
during
pregnancy
for
an
average
of
14
days
and
the
dams
were
allowed
to
deliver.
Within
48
hours
the
pups
were
killed
and
the
kidneys
examined.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
Not
a
full­
range
teratogenicity
study.
References:
Seipelt,
H.,
Zoellner,
K.,
Hilgenfeld,
E.,
and
Grossman,
H.
1969.
Untersuchungen
an
Niereg
neugeborener
Ratten
nach
chronischer
Harnstoffapplikation
beim
Muttertier.
Zschr
Urol
62:
623­
627.

(
d)
Species/
strain:
Chick
embryo
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
]
Route
of
Administration:
Injection
Duration
of
the
test:
<
text>
Exposure
period:
7th
 
20th
hour
of
incubation
Frequency
of
treatment:
Once
Doses:
50­
900
mg
Control
group:
Yes
[
];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL
Maternal
Toxicity:
<
text>
NOEL
teratogenicity:
<
text>
Results:
Among
132
embryos
78
showed
neural,
vascular
or
cardiac
abnormalities.
54
Urea
(
CAS
#
57­
13­
6)
Maternal
general
toxicity:
<
text>
Pregnancy/
litter
data:
<
text>
Fetal
data:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Fifty
to
900
mg
urea
dissolved
in
egg
albumin
was
injected
into
eggs
between
7th
and
20th
hour
of
incubation.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
Remarks:
The
results
indicate
that
urea
was
teratogenic
in
chick
embryo.
References:
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.

(
e)
Species/
strain:
Chick
embryo
Sex:
Female
[
];
Male
[
];
Male/
Female
[
];
No
Data
[
]
Route
of
Administration:
Injection
Duration
of
the
test:
<
text>
Exposure
period:
<
text>
Frequency
of
treatment:
Once
Doses:
200,
400,
800
and
1,200
mg/
kg
Control
group:
Yes
[
X];
No
[
];
No
Data
[
]
Concurrent
no
treatment
[
];
Concurrent
vehicle
[
];
Historical
[
]
NOEL
Maternal
Toxicity:
<
text>
NOEL
teratogenicity:
<
text>
Results:
Mortality
of
the
embryos
varied
8.8­
38.9%
dose
­
dependently.
The
mortality
in
the
control
group
was
6.1%.
In
the
treated
embryos,
the
plasma
T3
level
increased
and
T4
level
decreased.
Electron
microscopy
revealed
cytoplasmic
oedema,
mitochondrial
swelling
and
membrane
damage
in
thyroid
cells.
Maternal
general
toxicity:
<
text>
Pregnancy/
litter
data:
<
text>
Fetal
data:
<
text>
Method:
[
e.
g.
OECD,
other
(
with
the
year
of
publication
or
updating
of
the
method
used)]
Urea
was
injected
in
a
volume
of
0.05
ml
distilled
water
into
the
air
sack
of
the
egg
on
day
16,
17
and
18,
respectively,
of
incubation.
GLP:
Yes
[
]
No
[
]
?
[
X]
Test
substance:
Urea
of
p.
a.
grade
Remarks:
The
results
indicate
that
urea
was
foetotoxic
to
the
chicken.
References:
Mora,
S.,
Simon,
F.,
and
Kapp,
P.
1991.
Toxicological
model
investigation
on
chicken
embryo.
Acta
Vet
Scand.
Suppl.
87:
197­
198.
55
Urea
(
CAS
#
57­
13­
6)
5.10
OTHER
RELEVANT
INFORMATION
A.
Specific
toxicities
Type:
(
e.
g.
neurotoxicity,
immunotoxicity,
etc.)
Oncogenic
transformation
<
text>
Results:
<
text>
Remarks:
In
a
BALB/
c­
3T3
cell
transformation
assay,
urea
gave
a
negative
result
at
a
dose
range
2.5­
20
mg/
ml.
Reference:
Rundell,
J.
O.,
Guntakatta,
M.,
and
Matthews,
E.
J.
1983.
Criterion
development
for
the
application
of
BALB/
c­
3T3
cells
to
routine
Environ.
Sci.
Res.
27:
309­
324.

B.
Toxicodynamics,
toxicokinetics
Type:
(
e.
g.
neurotoxicity,
immunotoxicity,
etc.)
<
text>
Results:
Ruminants
Urea
is
generally
regarded
a
safe
and
efficient
feed
additive
(
substitute
for
natural
proteins)
for
ruminants.
The
toxicity
on
urea
depends
on
the
formation
of
ammonia.
Problems
occur
when
ingested
urea
releases
more
ammonia
than
the
rumen
microorganisms
can
fully
utilize
to
sythetize
amino
acids
and
protein.
Urea
can
cause
clinical
toxicosis
in
ruminants
at
0.3­
0.5
g/
kg
body
weight
and
death
at
1­
1.5
g/
kg.
Horses
are
less
susceptible.
Monogastic
animals,
such
as
swine
and
baby
calves,
are
not
affected
by
urea
except
for
a
mild
diuretic
action.
Humans
Urea
penetrates
rapidly
into
the
human
stratum
corneum;
penetration
is
enhanced
at
higher
urea
concentrations
and
with
time.
However,
transport
to
systemic
circulation
is
slow
and
limited.
About
5.9%
of
urea
applied
to
human
skin
was
recovered
in
the
urine.
Urea
is
extremely
soluble
in
water
and
is
adsorbed
and
distributed
rapidly
after
oral
doses.
In
man,
the
peak
concentration
in
blood
is
attained
in
30
to
90
minutes
after
a
peroral
dose.
The
dose
30
g
of
urea
(
about
0.5
g/
kg)
doubles
serum
urea
levels
in
20
min
and
a
maximum
level
of
94.6
mg/
100
ml
is
achieved
in
90
minutes
(
mean
control
36
mg/
100
ml).
Urea
is
an
endogenous
product
of
protein
and
aminoacid
catabolism
in
mammals.
The
physiological
concentration
of
urea
in
human
blood
is
3.3
­
6.7
mmol/
l
(
200­
400
mg/
l)
and
the
diurnal
excretion
in
urine
of
humans
is
20­
35
g.
56
Urea
(
CAS
#
57­
13­
6)
Rats
Subcutaneous
ingestion
of
urea
to
pregnant
rats
showed
that
the
substance
readily
penetrated
the
placenta
and
raised
fetal
urea
concentrations.
The
development
of
urea
cycle
enzymes
occurs
at
a
later
period
in
the
rat
fetus.
Remarks:
Oehme,
F.
W.
and
Barrett,
D.
S.
1986.
Veterinary
gastrointestinal
toxicology
In:
Gastrointestinal
Toxicology.
K.
Rozman
and
O.
Hänninen,
editors.
Elsevier
Science
Publishers
pp.
464­
513.
Wohlrab,
W.
and
Hassler,
N.
1981.
Penetrationskinetik
von
Harnstoff
in
die
menschliche
Haut.
Dermatol.
Mon.
Schr.
167:
277­
283.
Wohlrab,
W.
1988.
Welche
harnstoffkonzentration
is
für
die
externe
Therapie
notwendiz?
Dermatol.
Mon.
Schr.
174:
94­
98.
Harper,
H.
A.
and
Rodwell,
V.
W.
1977.
Review
of
Physiological
Chemistry,
16th
ed.,
Lange
Medical
Publications,
Los
Altos,
California
p.
625
Altman,
P.
L.
and
Dittmer,
D.
S.
1974.
Biology
Data
Book,
Vol.
III,
2nd
ed.
Federation
of
American
Societies
for
Experimental
Biology
pp.
1494
&
1501.
FDA,
PB­
288673.
1978.
Evaluation
of
the
Health
Aspects
of
Urea
as
a
Food
Ingredient.
Wohlrab,
W.
and
Schiemann,
S.
1976.
Untersuchungen
zum
Mechanisms
der
Harnstoffwirkung
auf
die
Haut.
Arch.
Derm.
Res.
255:
23­
30.
Feldman,
R.
and
Maibach,
H.
I.
1970.
Absorption
of
some
organic
compounds
through
the
skin
in
man.
J.
Invest.
Dermatol.
54:
399­
404.

*
5.11
EXPERIENCE
WITH
HUMAN
EXPOSURE
[
Describe
information
on
workplace
exposure
such
as
concentration
of
chemicals
in
the
workplace
or
indoor
environment
(
manufacturing,
maintenance
and
professional
use),
number
of
workers
(
in
ranges
for
each
situation),
frequency
and
duration
of
exposure,
if
available.
In
addition,
enter
details
of
effects
of
accidental
or
occupational
exposure,
epidemiological
and
clinical
studies,
case
reports,
etc.]

Results:
Remarks:
Urea
is
widely
used
at
10%
and
lower
concentrations
in
clinical
dermatology
as
a
keratolytic
agent;
it
hydrates
the
skin,
inhibits
epidermal
proliferation
and
possesses
antipruritic
and
antibacterial
properties.
At
higher
than
10%
concentration
urea
may
be
irritating
to
the
skin.
Urea
has
been
extensively
used
during
the
last
two
decades
in
the
treatment
of
dry
skin,
both
clinically
and
in
cosmetic
products.
No
long­
term
side
effects
have
been
found.
No
reports
of
contact
allergy
were
located
and,
in
spite
of
common
use
for
many
years,
no
epidermal
or
dermal
atrophy
has
been
reported.
57
Urea
(
CAS
#
57­
13­
6)
Intra­
amniotic
infusion
of
hypertonic
(
e.
g.,
30%)
urea
solution
has
been
clinically
used
for
the
termination
of
midtrimester
pregnancy.
Urea
is
used
in
therapeutic
ointments
and
creams.
Urea
concentration
range
is
40­
120
mg/
g
in
medical
products
marketed
in
Finland.
Urea
has
been
used
intravenously
as
an
osmotic
diuretic
in
treatment
of
oliguria
following
burns,
surgery
or
trauma;
in
promoting
diuresis
following
prostatectomy.
It
has
also
shown
to
be
effective
in
status
epilecticus
(
usual
intravenous
infusion,
100
mg
to
1
g/
kg
daily,
as
35%
solution
in
dextrose
injection
rate
not
exceeding
4
ml/
min).
Other
dose
information:
It
is
usually
administered
orally
as
a
single
dose
of
20
g
taken
2­
5
times
daily.
A
female
patient
with
an
idiopathic
syndrome
of
inappropriate
secretion
of
antidiuretic
hormone
(
SIADH)
was
successfully
treated
for
more
than
5
years
without
any
side
effects
with
oral
urea
(
30
g/
day)
allowing
her
a
normal
fluid
intake
(
1­
1.5
1/
day).
Urea
is
used
less
commonly
than
other
osmotic
agents
to
reduce
intraocular
pressure
and
vitreous
volume
prior
to
iridectomy
and
other
ocular
surgical
procedures.
Helicobacter
pylori
(
H.
pylori)
is
currently
known
as
an
important
cause
of
chronic
active
gastritis
and
peptic
ulceration.
H.
pylori
has
an
extremely
high
urease
activity.
Ammonia
generated
by
hydrolysis
of
urea
is
deleterious
to
the
gastric
mucosa.
Reference:
Müller,
K.
H.
1979.
Pflugshaupt
Ch.
Harnstoff
in
der
Dermatologie
I
(
Review).
Zbl.
Haut
142:
157­
168.
Greenhalf,
J.
O.
and
Diggory,
P.
L.
C.
1971.
Induction
of
therapeutic
abortion
by
intra­
amniotic
injection
of
urea.
Br.
Med.
J.
1:
28­
29.
Greenhalft,
J.
O.
1972.
Termination
of
pregnancy
during
mid­
trimester
by
intra­
amniotic
injection
of
urea.
Br.
J.
Clin.
Pract.
26:
24­
26.
Anteby,
S.
O.,
Segal,
S.,
and
Polishuk,
W.
Z.
1974.
Termination
of
midtrimester
pregnancy
by
intraamniotic
injection
of
urea.
Obstet.
Gynecol.
43:
765­
768.
Burkman,
R.
T.,
Bell,
W.
R.,
Atienza,
M.
F.
and
King,
T.
M.
1977.
Coagulopathy
with
midtrimester
induced
abortion:
Association
with
hyperosmolar
urea
administration.
Am.
J.
Obstet.
Gynecol.
127:
533­
536.
Registry
of
the
Medical
Products
Marketed
in
Finland,
National
Agency
for
Welfare
and
Health,
May
1992.
Osol,
A.,
Hoover,
J.
E.,
et
al.
(
eds.).
1975.
Remington's
Pharmaceutical
Sciences,
15th
ed.
Easton
Pennsylvania:
Mark
Publishing
Co.
p.
864,
as
cited
in
HSDB
1991.
American
Medical
Association,
AMA
Department
of
Drugs,
AMA
Drug
Evaluations,
3rd
ed.
1977.
Littleton,
58
Urea
(
CAS
#
57­
13­
6)
Massachusetts:
PSG
Publishing
Co.
Inc.
p.
936;
as
cited
in
HSDB
1991.
Swanbeck,
G.
1992.
Urea
in
treatment
of
dry
skin.
Acta
Derm
Venereal
(
Stockh)
Suppl.
177:
7­
8.
Stüttgen,
G.
1992.
Ergebnisse
und
Konsequenzen
eirer
langfristigen
Harnstofftherapie
für
die
medizinische
Praxis.
Hautarzt,
Suppl.
11:
9­
12.
Decaux
G.,
Prospect,
F.,
Penninckx,
R.,
Namias,
B.,
and
Soupart,
A.
1993.
5­
Year
treatment
of
the
chronic
syndrome
of
inappropriate
secretion
of
ADH
with
oral
urea.
Nephron
63:
468­
470.
Saita,
H.,
et
al.
1992.
Helicobacter
pylori
has
an
ulcerogenic
action
in
the
ischemic
stomach
of
rats.
J.
Clin.
Gastroenterol
14
(
Suppl.
1):
S122­
S126.
59
Urea
(
CAS
#
57­
13­
6)
6.
REFERENCES
Alchangian,
L.
V.,
et
at.
1986.
Vestn.
Dermatol.
Venerol.
9,
pp.
26­
29.

Altman,
P.
L.
and
Dittmar,
D.
S.
1974.
Biology
Data
Book,
Vol.
III,
2nd
Ed.
Federation
of
American
Societies
for
Experimental
Biology.
p.
1494.

American
Medical
Association,
AMA
Department
of
Drugs,
AMA
Drug
Evaluations,
3rd
ed.
1977.
Littleton,
Massachusetts:
PSG
Publishing
Co.
Inc.
p.
936;
as
cited
in
HSDB
1991.

Anteby,
S.
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