Document ID: EPA-HQ-OAR-2003-0118-0028
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-08-23T04:00Z

August
1,
2003
1
ATTACHMENT
1.

RECOMMENDATION
FOR
A
SHORT
TERM
EXPOSURE
LIMIT
(
STEL)
FOR
OCTAFLUOROPROPANE
(
R­
218)

The
STEL
for
octafluoropropane
(
R­
218)
was
determined
from
information
in
the
Background
Document
(
EPA,
1994).
Propane
was
used
as
a
surrogate
compound
in
determining
the
AEL
for
R­
218
to
be
1000
ppm.
Therefore,
the
STEL
was
set
at
3000
ppm,
which
is
three
times
the
AEL
set
by
the
Background
Document.
This
was
a
conservative
calculation
based
on
the
relative
low
toxicity
of
octafluoropropane.
A
summary
of
the
available
toxicity
studies
was
presented
in
the
ISCEON
89
®
SNAP
submission
and
detailed
below.

As
reported
by
the
submitter,
two
acute
inhalation
studies
in
the
rat
were
performed
by
McHale
(
1974)
and
3M
(
1993a)
and
one
in
the
mouse
by
Huntington
Research
Centre
(
1992)
(
ISCEON
®
89,
2003).
A
cardiac
sensitization
study
was
performed
in
the
dog
and
was
described
in
correspondence
between
the
submitter
and
3M
(
ISCEON
®
89,
2003).
A
repeat
exposure
test
of
10
days
duration
was
performed
using
rats
and
guinea
pigs
as
performed
by
McHale
(
1974)
(
ISCEON
89,
2003).
Genetic
toxicity
tests
(
reverse
mutagenicity
assay
in
bacteria
and
mouse
micronucleus
assay)
were
performed
by
Huntingdon
Research
Centre
(
1991)
(
ISCEON
®
89,
2003).
The
results
of
these
tests
are
described
below
as
summarized
by
the
submitter;
however,
the
raw
data
were
not
provided.

McHale
(
1974)
exposed
10
rats
(
sex
not
specified)
for
one
hour
to
800,000
ppm
octafluoropropane
in
20%
oxygen.
No
mortality
was
observed.
Exposed
rats
appeared
hyperactive
initially,
then
appeared
hypoactive,
with
hyperemia
and
closed
eyes.
Growth
curves,
as
measured
by
body
weight
gain,
of
the
exposed
animals
were
comparable
to
the
controls
during
the
14­
day
post­
exposure
observation
period.

Rhône­
Poulenc,
the
submitter,
corresponded
with
3M
Corporation
(
1993a)
and
received
acute
inhalation
toxicity
data
on
the
rat.
Ten
Sprague­
Dawley
rats
(
5
males
and
females
each)
were
exposed
to
110,000
ppm
octafluoropropane
for
4
hours.
No
mortality
was
observed.
Body
weight
gains
were
reduced
in
the
females
as
compared
to
controls
(
significance
was
not
reported).
Food
consumption
was
reportedly
reduced
the
day
after
exposure.
Lung
congestion
was
reported
in
one
of
the
rats
(
sex
and
time
of
necropsy
not
reported).
The
study
authors
concluded
that
octafluoropropane
is
a
simple
asphyxiant.

A
micronucleus
study
was
performed
(
Huntingdon
Research
Centre
1991)
in
which
30
mice
were
exposed
to
800,000
ppm
octafluoropropane
(
in
20%
oxygen)
for
6
hours.
No
mortality
was
observed.
An
initial
onset
of
hyperactivity
was
observed.
Five
animals
of
each
sex
were
sacrificed
at
24,
48,
and
72
hours.
The
lungs,
liver,
and
kidneys
from
animals
sacrificed
at
72
hours
were
preserved
and
no
abnormalities
were
noted.
No
increases
in
the
number
of
micronucleated
polychromatic
or
normochromatic
erythrocytes
were
observed.
August
1,
2003
2
Rhône­
Poulenc,
the
submitter,
again
corresponded
with
3M
Corporation
(
1993b)
and
received
data
on
a
cardiac
sensitization
study
in
the
dog.
Dogs
were
exposed
by
inhalation
to
50,000,
100,000,
200,000,
300,000,
and
400,000
ppm
octafluoropropane
followed
by
an
injection
of
adrenaline
(
concentration
unspecified).
Oxygen
was
maintained
above
22%
(>
100,000
ppm
oxygen
was
added
to
the
exposure
chamber).
Eight
dogs
were
exposed
to
the
highest
dose,
but
6
dogs
were
exposed
to
the
remaining
doses.
One
positive
(
multiple
and
multifocal
ectopic
beats)
and
one
questionable
response
were
observed
in
the
400,000­
ppm
exposure
group.
The
NOAEL
was
300,000
ppm
and
the
LOAEL
was
400,000
ppm
due
to
an
increase
in
cardiac
effects
in
2/
8
dogs.

The
repeat
exposure
test
utilized
rats
(
10/
sex)
and
guinea
pigs
that
were
exposed
to
113,000
ppm
octafluoropropane
continuously
via
inhalation
(
McHale
1974).
No
signs
of
toxicity,
or
changes
in
hematological
or
histopathological
endpoints
due
to
octafluorpropane
exposure
were
observed.

Intraocular
injection
of
0.4
mL
of
octafluoropropane
into
rabbit's
eyes
caused
temporary
haziness
of
the
vitreous
humor
that
cleared
in
an
average
of
28
days
(
Lincoff
and
Kreissig
1981).
No
cellular
damage
or
membrane
damage
was
observed.

Reverse
mutation
tests
in
Salmonella
strains
TA98,
TA100,
TA1535,
and
TA1537
were
negative
at
doses
up
to
800,000
ppm
in
air
(
Huntingdon
Research
Centre
1991;
3M
1993c).
E.
coli
(
strains
unreported)
exposed
to
octafluoropropane
(
exposure
was
via
bubbling
of
the
gas
through
the
bacterial
culture
at
an
unreported
concentration)
exhibited
a
change
in
mannitol
fermentation,
causing
the
investigators
to
conclude
that
the
compound
had
affected
gene
expression
by
mutating
the
bacterial
DNA
(
Fuerst
and
Laundry
1966;
Laundry
and
Fuerst
1967).

No
subchronic,
chronic,
carcinogenic,
developmental,
or
reproductive
studies
were
identified
in
any
animal
model
using
octafluoropropane.
Further,
no
exposure
studies
in
humans
have
been
performed
(
an
exception
may
be
the
NASA
information
referred
to
below,
but
it
does
not
appear
that
they
have
actually
done
studies
on
their
astronauts).
The
submitter
has
established
an
internal
8­
hour
TWA
Occupational
Exposure
Limit
of
1000
ppm
(
7690
mg/
m3).
Perfluoropropane
(
octafluoropropane)
is
used
by
the
Russians
in
their
space
program
with
a
maximum
limit
of
19.51
ppm
(
150
mg/
m3).
The
National
Aeronautics
and
Space
Administration
has
set
a
Spacecraft
Maximum
Allowable
Concentration
for
a
1­
hour
exposure
of
11,000
ppm
based
on
the
McHale
(
1974)
study
NOAEL
of
113,000
ppm
with
an
uncertainty
factor
of
10
for
interspecies
extrapolation
and
intraspecies
variations
(
NRC
2000).
August
1,
2003
3
REFERENCES
3M
1993.
3M
Correspondence
with
Rhône­
Poulenc
on
May
13,
1993a;
July
7,
1993b;
September
3,
1993c.

Fuerst
R
and
MM
Laundry
1966.
Gases
affecting
bacterial
survival.
Develop
Ind
Microbiol.
8:
305­
312.

Huntingdon
Research
Centre
1992.
Unpublished
data.

Huntingdon
Research
Centre
1991.
Unpublished
data.

ISCEON
®
89,
2003.
Application
to
SNAP
for
approval
of
ISCEON
®
89
submitted
by
Fluorinated
Consumer
Products.

Landry
MM
and
R
Fuerst.
1967.
Gas
ecology
of
bacteria.
Develop
Ind
Microbiol.
9:
370­
380.

Lincoff
A
and
I
Kreissig
1981.
Intravitreal
behavior
of
perflourocarbons.
Dev
Ophthalmol.
2:
17­
23.

McHale
ET.
1974.
Life
support
without
combustion
hazard.
Fire
Technology.
10:
15­
24.

National
Research
Council.
2000.
Spacecraft
Maximum
Allowable
Concentration
for
Selected
Airborne
Contaminants.
Volume
1.
National
Academy
of
Sciences,
Washington,
DC.
pp
148.