Propionaldehyde
WEEL
Document
September
12,
2000
1
Workplace
Environmental
Exposure
Level
­
Propionaldehyde
I.
IDENTIFICATION
Chemical
Name:
Propionaldehyde
Synonyms:
1­
Propanal,
methylacetaldehyde,
propylaldehyde
CAS
Number:
123­
38­
6
Molecular
Formula:
C3H6O
Structural
Formula:
CH3­
CH2­
CH=
O
II.
PHYSICAL
AND
CHEMICAL
PROPERTIES
(
1,2,3,4,5)

Physical
State
and
Appearance:
Colorless
liquid
Odor
Description:
Suffocating,
pungent,
irritating,
unpleasant
Odor
Thresholds:
Absolute
perception
limit:
0.009
ppm
50%
recognition
limit:
0.040
ppm
100%
recognition
limit:
0.080
ppm
Molecular
Weight:
58.1
Conversion
Factors:
1
ppm
=
2.38
mg/
m
3
1
mg/
m
3
=
0.42
ppm
Melting
Point:
­
81
º
C
at
760
mm
Hg
Boiling
Point:
49
º
C
at
760
mm
Hg
Vapor
Pressure:
235
mm
Hg
at
20
º
C
317
mm
Hg
at
25
º
C
687
mm
Hg
at
45
º
C
Flash
Point:
<
20
º
F
(<
­
7
º
C)
(
Open
Cup)
Specific
Gravity:
0.807
(
Water
=
1)
Vapor
Density:
2.0
Solubility:
Propionaldehyde
is
miscible
with
alcohol,
chloroform,
and
ether;
20
g
soluble
in
100
g
water.
Its
solubility
in
water
is
approximately
20%
by
weight.
Reactivity
and
Incompatibilities:
Reacts
vigorously
with
oxidizers;
polymerization
may
occur
in
the
presence
of
acids
or
caustics.
Contamination
with
basic
materials,
mineral
acids
or
iron
oxides
can
result
in
a
rapid
exothermic
reaction.
Oxidation
can
cause
formation
of
hazardous
peroxides
or
peracids.(
6)

III.
USES(
3)

Propionaldehyde
is
used
primarily
as
a
reactive
intermediate
in
the
manufacture
of
propanol,
propionic
acid,
rubber
chemicals,
polyvinyls
and
other
plastics,
fragrances,
and
fungicides.
Production
and
conversion
to
other
chemicals
necessarily
take
place
in
closed
systems
because
of
the
volatile
and
flammable
nature
of
this
chemical.
Propionaldehyde
is
transported
between
site
locations
by
pipeline
or
bulk
carrier;
these
practices
minimize
workplace
exposure.
Propionaldehyde,
as
a
reactive
intermediate,
is
not
directly
contained
in
products
reaching
the
consumer.
Propionaldehyde
WEEL
Document
September
12,
2000
2
Propionaldehyde
occurs
naturally
in
apple
aroma
and
has
been
identified
as
a
volatile
emission
of
arboreous
plants.
It
is
found
in
the
essential
oils
of
camphor,
Rosa
centrifolia,
Clary
sage,
Pinus
excelsa,
Pinus
silvestris,
and
other
plants.

III.
ANIMAL
TOXICOLOGY
DATA
A.
Acute
Toxicity
and
Irritancy
1.
Oral
Toxicity
Rats:
LD50
=
1410
mg/
kg
(
males)
(
7,8)

LD50
=
1690
mg/
kg
(
females)
(
9)

2.
Eye
Toxicity
Rabbits:
A
volume
of
0.1
ml
propionaldehyde
instilled
into
the
corneal
sac
resulted
in
minor
transient
corneal
injury
and
iritis.
Moderate
to
severe
conjuctival
irritation
was
observed
within
1
to
48
hr.
At
24
to
72
hr,
hemorrhages
were
apparent
on
the
nictitating
membranes.
Within
7
days,
only
minor
conjuctival
redness
remained;
all
eyes
were
normal
at
10
and
14
days
after
exposure.
Instillation
of
a
lesser
volume
(
0.01
ml)
had
similar
results
but
more
rapid
recovery;
all
eyes
were
normal
within
7
days
after
exposure.
(
9)

3.
Skin
Absorption
Rabbits:
LD50
=
2460
mg/
kg
(
females);
2000
mg/
kg
killed
1
of
3
males
(
8)

LD50
=
5.0
ml/
kg
(
4035
mg/
kg)
(
males)
(
7,8)

4.
Skin
Irritation
Rabbits:
Application
of
0.5
ml
to
covered
rabbit
skin
for
a
4
hr
contact
period
produced
minor
to
moderate
redness
and
moderate
edema.
Superficial
necrosis
and
desquamation
developed
within
7­
14
days.
At
14
days,
there
was
no
edema
or
redness;
fissuring,
scabs,
or
alopecia
were
apparent
on
a
few
animals.(
9)

5.
Skin
Sensitization
No
animal
data
is
available.

6.
Inhalation
Toxicity
Rats
exposed
to
16,000
ppm
died
within
2.25
hr,
8000
ppm
killed
5/
6
rats
within
4
hr.
There
was
no
mortality
among
rats
exposed
to
4000
ppm
for
4
hr.
Substantially
saturated
vapor
dynamically
generated
at
room
temperature
(
approximately
300,000
ppm)
killed
6/
6
rats
in
10
min,
2/
6
in
5
min,
and
0/
5
in
2
min.(
8)
Propionaldehyde
WEEL
Document
September
12,
2000
3
The
vapor
concentration
of
propionaldehyde
capable
of
causing
a
50%
reduction
in
respiratory
rate
(
RD50)
during
a
10­
minute,
whole
body
exposure
was
2070
ppm
(
95%
confidence
interval
1803
to
2402)
in
B6C3F1
male
mice,
and
2052
ppm
(
95%
confidence
interval
1625­
3040)
in
male
Swiss­
Webster
mice.(
10)
The
RD50
in
Fischer
F344
rats
was
6789
ppm.(
11)

7.
intraperitoneal
Toxicity
Mice:
LD50
=
960
mg/
kg(
12)

B.
Subacute
Toxicity
Propionaldehyde
was
administered
by
inhalation
to
male
and
female
Alderley
Park
SPF
rats
6
hr/
day
for
6
consecutive
days
at
1300
ppm.
There
were
no
deaths;
animals
did
not
gain
weight
during
the
exposure
interval.
Upon
necropsy,
organs
appeared
normal.
Microscopic
examination
of
tissues
revealed
cell
vacuolization
of
the
liver.(
13)

Male
and
female
Alderley
Park
SPF
rats
were
exposed
to
90
ppm
for
6
hr/
day,
5
days/
week,
for
4
weeks
(
20
exposures).
There
were
no
deaths
and
animals
did
not
exhibit
signs
of
toxicity
during
the
exposure
interval.
Urinalysis
and
hematology
tests
were
normal.
Upon
necropsy,
organs
appeared
normal.
Microscopic
examination
of
tissues
revealed
no
pathology.(
13)

C.
Subchronic
Toxicity
Groups
of
male
and
female
CD
rats
were
exposed
to
propionaldehyde
vapor
at
concentrations
of
0,
150,
750,
or
1500
ppm
for
6
hr/
day,
7
days/
week.
Males
were
exposed
for
52
days;
females
were
exposed
for
48
days
and
then
held
for
a
6­
day
recovery
interval
before
sacrifice.
Animals
did
not
display
overt
signs
of
toxicity
at
any
time
during
the
study.
Body
weight
gains
and
food
consumption,
however,
were
decreased
in
females
in
the
750
and
1500
ppm
groups
during
the
first
week
of
exposure.
Microscopic
examination
revealed
treatment­
related
effects
on
the
nasal
epithelium
in
the
anterior
two
sections
of
the
nasal
cavity
in
both
sexes
in
all
propionaldehyde­
exposed
groups.
Vacuolization
of
the
nasal
epithelium
was
primarily
evident
in
the
low
and
intermediate
exposure
groups;
atrophy
was
observed
in
the
intermediate
and
high
exposure
groups.
The
injury
appeared
to
be
diminished
in
females,
possibly
as
a
result
of
the
6­
day
recovery
interval.
(
14)

No
data
available.

D.
Chronic
Toxicity/
Carcinogenicity
No
data
available.
Propionaldehyde
WEEL
Document
September
12,
2000
4
E.
Reproductive/
Developmental
Toxicity
1.
One­
Generation
Inhalation
Study
(
Rat)

Male
and
female
rats
were
exposed
to
propionaldehyde
by
inhalation
for
6
hr
per
day,
7
days
per
week,
at
concentrations
of
0,
150,
750,
or
1500
ppm.
Males
received
52
consecutive
daily
exposures;
females
were
exposed
through
gestation
day
20,
for
a
maximum
of
48
days.
Females
were
allowed
to
litter.
Pup
body
weight,
viability,
and
survival
were
monitored
from
birth
until
post­
natal
day
4,
when
both
females
and
their
offspring
were
sacrificed
and
subjected
to
necropsy.
No
significant
effects
of
exposure
were
noted
on
any
reproductive
parameter
assessed.
Mating
index
and
fertility
index
for
males
and
females,
and
the
gestation
index
for
females,
were
not
affected.
Litter
size
and
viability
were
similar
among
all
groups;
pup
body
weights
were
not
affected
by
exposure,
although
the
body
weight
gain
of
pups
from
the
1500
ppm
group
were
slightly
depressed.(
14)

2.
Intraamniotic
Injection
Developmental
Study
(
Rat)

Timed­
pregnant
female
Sprague­
Dawley
rats
were
laparotomized
under
anesthesia
on
gestation
day
13.
Embryos
in
one
uterine
horn
received
an
intraamniotic
injection
of
propionaldehyde
at
doses
of
10,
100,
or
1000
ug/
embryo.
Females
were
killed
on
gestation
day
20.
Uterine
horns
were
removed
and
the
number
of
dead
or
resorbed
fetuses
were
determined.
Live
fetuses
were
examined
for
external
malformations.
Propionaldehyde
treatment
resulted
in
a
dose­
dependent
increase
in
embryo
mortality.
The
increase
in
embryolethality
was
significant
at
the
highest
dose
of
1000
ug/
embryo
when
compared
to
saline­
injected
controls.
There
was
no
increase
in
fetal
malformations
up
to
the
highest
concentration
tested,
1000
ug/
embryo.(
15)

D.
Genotoxicity/
Mutagenicity
1.
In
Vitro
Studies
Propionaldehyde
was
negative
in
seven
strains
of
Salmonella
typhimurium
at
concentrations
up
to
10,000
ug/
plate,
in
the
presence
and
absence
of
rat,
mouse,
or
hamster
S­
9
metabolic
activation.(
16­
19)
Propionaldehyde
induced
a
dose­
dependent
increase
in
mutation
frequency
in
Chinese
hamster
V79
cells
in
the
absence
of
metabolic
activation.(
20)
Chinese
hamster
ovary
(
CHO)
cells
exposed
to
propionaldehyde
displayed
a
weak
increase
in
the
incidence
of
lagging
chromosomes
when
compared
to
untreated
controls.
There
was,
however,
no
difference
between
control
and
treated
cell
cultures
in
the
frequency
of
chromatin
bridges
or
lagging
fragments.(
21)
Propionaldehyde
WEEL
Document
September
12,
2000
5
1.
In
Vivo
Studies
Propionaldehyde
was
administered
to
groups
of
male
and
female
Swiss­
Webster
mice
as
a
single
intraperitoneal
injection
at
doses
of
240,
480,
or
768
mg/
kg
(
25%,
50%
or
80%
of
the
LD50,
respectively).
Animals
were
sacrificed
at
12,
24,
and
48
hr
after
treatment;
bone
marrow
was
collected
and
a
minimum
of
1000
polychromatic
erythrocytes
were
examined
for
the
presence
of
micronuclei.
Although
the
high
dose
males
had
a
higher
incidence
of
micronuclei
than
vehicle
controls,
the
overall
incidences
of
micronuclei
and
the
distribution
of
micronuclei
were
within
normal
ranges.
Propionaldehyde
was
not
considered
to
be
an
inducer
of
micronuclei
under
the
conditions
of
this
in
vivo
test.(
22)

D.
Metabolism/
Pharmacokinetics
Propionaldehyde
is
a
reactive
molecule
and
readily
oxidizes
to
propionic
acid
via
aldehyde
dehydrogenase
(
ALDH);
propionaldehyde
has
been
demonstrated
to
be
a
substrate
for
ALDH.
Propionaldehyde
dehydrogenase
activity
has
been
identified
in
tissue
preparations
from
mice(
23)
,
rats(
24,25),
and
humans(
26).

Retention
of
propionaldehyde
in
the
respiratory
tract
of
anesthetized
dogs
was
75
to
80%
of
the
inhaled
dose
at
concentrations
between
250
and
1000
mg/
m
3
(
100
to
400
ppm).
Similar
retentions
were
also
measured
in
dogs
at
tidal
volumes
ranging
from
approximately
100
to
200
ml.(
27)
Propionaldehyde
acted
as
a
vasopressor
agent
when
injected
into
anesthetized
dogs(
28)
and
rats(
29).

V.
HUMAN
USE
AND
EXPERIENCE
Propionaldehyde
is
a
food
flavoring
agent
and
is
a
naturally
occurring
coffee
and
apple
aroma
constituent.
Propionaldehyde
is
a
product
of
wood,
gasoline,
diesel
and
polyethylene
combustion.
Average
concentrations
detected
in
the
gaseous
phase
among
atmospheric
emissions
during
combustion
of
four
gasoline
fuels
were
2.4,
2.8,
4.9,
and
3.3
ug/
km
traveled.
Propionaldehyde
was
emitted
at
a
rate
of
0.002
g/
min
from
smoldering
green
ash
wood.
Red
oak
wood
used
as
wood
stove
fuel
emitted
propionaldehyde
at
a
rate
of
0.050
and
0.009
g/
min
for
the
first
2
minutes
of
the
burn,
and
thereafter,
respectively.(
3)

According
to
the
National
Ambient
Volatile
Organic
Compounds
(
VOCs)
Database,
the
median
urban
concentration
of
propionaldehyde
was
17.2
ppb
for
22
samples.
Concentrations
in
Jones
State
Forest,
TX
ranged
from
1.8
to
39.9
ppb,
with
an
average
of
18.8
ppb
for
5
samples.
The
median
remote
atmospheric
concentration
of
propionaldehyde
was
0.993
ppb
for
3
samples.(
3)

Office
workers
for
the
USEPA
at
65
locations
in
3
headquarter
buildings
were
exposed
to
average
concentrations
of
0.91
ug/
m
3
(
0.373
ppb)
propionaldehyde.(
30)

Minimal
occupational
exposure
is
likely
to
occur
at
sites
where
propionaldehyde
is
produced
or
used
as
a
chemical
intermediate.
In
the
17­
year
period
between
1975
and
1992,
a
total
of
73
personnel
samples
had
been
taken
within
the
Propionaldehyde
WEEL
Document
September
12,
2000
6
"
Oxo"
production
unit
of
Union
Carbide.
Of
these,
62
(>
85%)
were
below
the
detection
limit
of
0.01
ppm.
The
maximum
TWA
measured
over
this
interval
was
26
ppm
and
the
geometric
mean
for
all
73
TWA
determinations
was
0.02
ppm.
In
the
same
timeframe,
16
TWA
determinations
were
made
within
the
In­
Plant
Distribution
Department.
Of
these,
8
(
50%)
were
below
the
detection
limit
of
0.01
ppm.
In
one
or
two
instances,
excursions
in
the
range
of
100
ppm
were
determined,
but
the
geometric
mean
for
all
16
samples
was
still
in
the
range
of
1
ppm.(
31)

At
one
facility,
propionaldehyde
was
charged
from
drums
to
a
reactor
in
a
chemical
synthesis
batch
process
that
is
run
intermittently.
Workers
wear
fullface
supplied­
air
respirators
and
protective
clothing
during
transfer
operations.
Air
sampling
was
conducted
during
the
30­
minute
task;
the
average
concentration
on
one
occasion
was
8.4
ppm,
while
51
ppm
was
obtained
on
another
occasion.
After
one
operation
was
completed,
air
sampling
revealed
that
propionaldehyde
levels
were
less
than
0.2
ppm,
however,
a
lingering
offensive
odor
was
noted
throughout
the
area.(
32)

VI.
RATIONALE
As
with
other
aldehydes,
propionaldehyde
is
an
irritant
to
the
eyes,
skin,
and
upper
respiratory
tract.
Toxicological
data
indicate
that
adverse
acute
and
chronic
effects
occur
only
at
fairly
high
dosages,
and
overall
toxicity
is
moderate.
Propionaldehyde
is
not
a
reproductive
or
developmental
toxicant
and
does
not
produce
systemic
toxicity
in
subchronic
inhalation
studies.

Propionaldehyde
is
anticipated
to
be
metabolized
and
is
not
expected
to
accumulate
in
humans.
The
low
acute
lethality
potential
and
lack
of
systemic
effects
suggest
that
the
WEEL
can
be
based
on
ocular
and
upper
respiratory
tract
irritancy.
Using
the
correlation
between
RD50
measurements
and
exposure
limits(
33),
a
WEEL
between
15
and
50
ppm
would
be
indicated.
This
range
is
within
the
TWA
range
recommended
by
Steinhagen
and
Barrows(
10),
and
less
than
TWA
recommended
by
Alarie(
34).
However,
in
a
subchronic
study,
rhinitis,
and
atrophy
and
vacuolization
of
the
olfactory
epithelium
were
observed
in
rats
exposed
to
750
ppm.
Minimal
to
mild
vacuolization
of
the
olfactory
epithelium
was
noted
in
rats
exposed
to
150
ppm.
These
data
suggest
that
a
WEEL
guide
of
15
ppm
should
be
recommended
to
prevent
irritation
and
possible
minimal
changes
in
the
nasal
cavity.

It
must
be
noted
that
obligate
nose
breathing
in
rodents
results
in
a
higher
delivered
dose
to
the
nasal
epithelium
than
in
man;
rats
and
mice
therefore
exhibit
a
greater
susceptibility
to
nasal
lesions
than
humans.
The
WEEL
value
proposed
is
extremely
conservative
in
terms
of
being
protective
of
worker
health.

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