Document ID: EPA-HQ-OPP-2002-0346-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-12-03T05:00Z

Page
1
of
8
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
April
8,
2002
MEMORANDUM
FROM:
Kathryn
Boyle,
CoChair
IIFG
and
Kerry
Leifer,
CoChair
IIFG
TO:
Robert
Forrest,
Chief
Minor
Use,
Inerts,
and
Emergency
Response
Branch
SUBJECT:
November
27,
2001,
Meeting
of
the
IIFG
Decision
Memo
Please
find
attached
the
Inert
Ingredient
Focus
Group
recommendations
for
the
inert
and
active
ingredient
propionic
acid
and
its
calcium
and
sodium
salts.
Page
2
of
8
INERT
INGREDIENT
FOCUS
GROUP
DECISION
DOCUMENT
for
Propionic
Acid
and
its
Calcium
and
Sodium
Salts
Petition
No.:
6F4770
Tolerance
Reassessments?:
yes
Chemical
Name(
s):
propionic
acid
propionic
acid,
sodium
salt
propionic
acid,
calcium
salt
CAS
Index
Name:
propanoic
acid
Chemical
Category/
Group:
organic
acid
and
salts
CAS
Reg.
No.:
propionic
acid
(
79­
09­
4)
propionic
acid,
sodium
salt
(
137­
40­
6)
propionic
acid,
calcium
salt
(
4075­
81­
9)

PC
Code:
propionic
acid
(
active:
077702,
inert:
900316)
propionic
acid,
sodium
salt
(
877703)
propionic
acid,
calcium
salt
(
877701)

HPV
Chemical:
yes
(
acid
and
calcium
salt)
Data
Posted:
no
Use
Pattern
(
pesticidal):
As
an
active
ingredient,
propionic
acid
is
used
to
control
fungi
and
bacteria
in
stored
grains,
hay,
grain
storage
areas,
poultry
litter,
and
drinking
water
for
livestock
and
poultry.
Propionic
acid
is
also
used
in
food­
contact
surface
sanitizing
solutions.
The
current
petition
is
requesting
use
on
sugarbeets,
potatoes,
and
sweet
potatoes.

Use
Pattern
(
non­
pesticidal):
Propionic
acid
and
its
sodium
and
calcium
salts
are
affirmed
GRAS
direct
food
additives
(
21
CFR
184.1081,
184.1221,
184.1784)
used
as
food
and
feed
preservatives.

Introduction:
Page
3
of
8
The
meeting
of
the
Inert
Ingredient
Focus
Group
to
discuss
propionic
acid
was
held
on
November
27,
2001.
Focus
Group
members
in
attendance
were:
Kathryn
Boyle
(
RD),
Kerry
Leifer
(
RD),
Robert
Forrest
(
RD),
Mark
Perry
(
SRRD),
Pauline
Wagner
(
HED),
Tom
Brennan
(
HED)
and
Sid
Abel
(
EFED).
The
presenters
were:
Michele
Mahoney
(
EFED)
and
Christina
Jarvis
(
HED).
The
Executive
Secretaries
were
Steve
Schaible
(
RD)
and
Jeanie
McAndrew
(
RD).
Also
in
attendance
was
Stephen
Dapson
(
HED).
This
meeting
addressed
the
available
human
health
effects
and
ecological
information
on
propionic
acid
(
and
its
calcium
and
sodium
salts),
considering
both
active
and
inert
uses,
to
determine
if
the
tolerance
exemptions
established
prior
to
the
passage
of
FQPA
could
continue
to
be
supported
[
refer
to
40CFR
180.1001(
c)
and
180.1023].
The
List
classification
of
propionic
acid
and
its
salts
was
also
discussed.

Calcium
and
sodium
propionate
are
not
currently
registered
pesticide
active
ingredients,
and
tolerance
exemptions
that
were
established
for
calcium
and
sodium
propionate
[
40
CFR
180.2(
a)
and
40
CFR
180.1015]
have
been
revoked.
For
the
purposes
of
this
evaluation
however,
these
sodium
and
calcium
salts
are
considered
representative
of
the
acid
form.
Propionic
acid
occurs
naturally
in
animal
and
dairy
products,
such
as
butter
and
cheese.
Propionic
acid
and
its
salts
are
also
consumed
as
added
ingredients
in
jams,
jellies,
and
jelly­
filled
baked
goods,
and
as
antimicrobial
agents
in
cheese
and
bread.
Propionic
acid,
calcium
propionate,
and
sodium
propionate
have
been
affirmed
as
Generally­
Recognized­
As­
Safe
(
GRAS)
by
the
Food
and
Drug
Administration
(
FDA)
for
use
as
a
direct
food
additive.
This
GRAS
finding
specifies
that
"
The
ingredient
is
used
in
food
with
no
limitation
other
than
current
good
manufacturing
practice."

As
indicated
above,
data
from
the
HPV
Challenge
Program
is
available
for
propionic
acid
and
its
sodium/
calcium
salts.
HPV
data
for
propionic
acid
include
acute
toxicity,
mutagenicity,
ecotoxicity,
and
environmental
fate.
For
the
sodium
salt,
acute
toxicity,
mutagenicity,
and
ecotoxicity
data
are
available;
and
for
the
calcium
salt,
acute
toxicity,
developmental/
reproductive
toxicity,
and
mutagenicity
data
have
been
provided.
HPV
data
on
two
propionic
acid
derivatives
were
also
considered
in
this
evaluation.
Additional
data
received
through
the
HPV
Challenge
Program
on
propionic
acid
and
its
sodium
and
calcium
salts
may
have
potential
impacts
on
the
Agency's
tolerance
reassessment
decision
for
these
chemicals.
The
Agency
may
revise
or
update
their
tolerance
decision
for
propionic
acid
and
its
sodium
and
calcium
salts
as
considered
appropriate
by
any
incoming
data
generated
as
part
of
this
program.

1.
Physical/
Chemical
Properties:

Propionic
Acid
Parameter
Test
Results
physical
form:
liquid
molecular
weight:
74.08
solubility
(
water):
determined
to
be
completely
soluble
Page
4
of
8
vapor
pressure:
3
mm
Hg
@
20
oC
melting
point:
­
21.5
oC
boiling
point:
140.7
oC
2.
Toxicological
Profile:

The
toxicological
database
for
propionic
acid
was
determined
to
be
adequate
for
reregistration
eligibility
at
the
time
the
RED
was
completed
(
9/
91).
A
comprehensive
search
of
the
open
literature
from
1991
forward
and
a
search
for
in­
house
toxicological
data,
failed
to
reveal
new
information
on
propionic
acid
which
would
compromise
the
toxicological
findings
in
the
RED
document.
Therefore,
the
toxicological
findings/
data
from
the
propionic
acid
RED
(
which
also
addresses
the
calcium
and
sodium
salts)
have
been
used
for
the
current
evaluation.

Acute
Toxicity:
Technical
propionic
acid
is
of
moderate
to
low
acute
toxicity
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
(
toxicity
category
of
III),
and
is
not
a
skin
sensitizer.
However,
propionic
acid
is
acutely
toxic
in
eye
and
dermal
irritation
tests
(
toxicity
category
1).

Subchronic
Toxicity:
No
subchronic
toxicity
data
are
available
on
propionic
acid
itself,
however,
data
on
calcium
and
sodium
propionate
can
be
used
to
assess
subchronic
toxicity.
Rats
fed
calcium
or
sodium
propionate
at
one
percent
of
the
diet
(
equivalent
to
750
mg/
kg/
day
of
propionic
acid)
for
four
weeks
followed
by
three
percent
(
equivalent
to
1200
mg/
kg/
day
of
propionic
acid)
for
three
weeks
showed
no
changes
in
weight
gain
compared
to
the
controls.
Rats
fed
five
percent
propionic
acid
in
the
diet
(
approximately
5000
mg/
kg
body
weight)
for
110
days
developed
lesions
of
the
forestomach.

Propionic
acid
was
given
in
the
feed
to
dogs
at
220,
735,
or
2066
mg/
kg/
day
for
90
days.
The
high
dose
dogs
showed
reduced
food
consumption,
increased
incidence
of
epithelial
hyperplasia
in
the
esophagus,
and
increased
nitrite
in
the
urine.
These
effects
were
no
longer
present
in
dogs
held
for
a
six
week
recovery
period.
A
limited
study
with
calcium
propionate
in
dogs
for
90
days
showed
vomiting
and
diarrhea
in
animals
fed
2523
mg/
kg/
day.
A
human
adult
male
was
fed
6.0
grams
sodium
propionate
a
day,
with
slightly
alkaline
urine
as
the
only
effect.

Chronic
Toxicity:
Twenty
male
rats
per
group
were
fed
four
percent
propionic
acid
in
the
diet
for
two
years.
The
highest
dose
animals
had
hyperplasia
and
hyperplastic
ulcers
in
the
forestomach.
Available
data
on
calcium
and
sodium
propionate
indicate
the
following:

Rats
fed
bread
containing
sodium
propionate
(
4000
mg/
kg/
day)
for
a
year
showed
no
adverse
effects,
nor
did
rats
fed
a
similar
diet
for
32
weeks,
other
than
an
initial
depression
of
growth.

Reproduction,
and
Teratology:
Page
5
of
8
No
maternal
or
fetal
effects
were
seen
upon
feeding
calcium
propionate
to
pregnant
animals
at
rates
up
to
300
mg/
kg/
day
for
rats
and
mice,
or
up
to
400
mg/
kg/
day
for
hamsters
and
rabbits.

No
teratogenicity
was
found
in
developing
chick
embryos
when
up
to
100
mg/
kg
calcium
propionate
was
injected
into
the
yolk
or
air
cell,
although
there
was
increased
mortality
at
5
and
10
mg/
kg.

Mutagenicity:
Propionic
acid
gave
negative
results
in
mutagencity
assays
in
five
strains
of
S.
typhimurium
and
one
strain
of
S.
cerevisiae,
with
and
without
activation.

Additional
data
on
calcium
and
sodium
propionate
indicated
that
both
tested
negative
for
mutagenicity
in
S.
typhimurium
and
S.
cerevisiae.

Metabolism:
Propionic
acid
is
rapidly
absorbed
from
the
mammalian
gastrointestinal
tract.
Propionic
acid
is
a
normal
intermediary
metabolite
in
the
body.
It
is
utilized
by
most
organs
and
tissues,
and
can
be
metabolized
to
glucose,
carbohydrates,
amino
acids,
and
lipids.
It
is
produced
in
large
quantities
in
ruminants,
and
is
one
of
the
metabolic
products
from
the
breakdown
of
several
amino
acids
in
nonruminants.
Propionic
acid
is
formed
in
the
oxidation
of
fatty
acids
and
from
the
side
chain
of
cholesterol.

1.
Hazard
Characterization:

Propionic
acid,
calcium
propionate
and
sodium
propionate
have
FDA
affirmed
GRAS
status
as
a
direct
food
additive.
Neither
propionic
acid
nor
its
salts
are
expected
to
result
in
any
adverse
health
effects
via
the
food,
drinking
water,
or
residential
exposure
pathways.

2.
Type
of
risk
assessment:
qualitative
3.
Sensitivity
of
Infants
and
Children:

These
chemicals
have
low
toxic
potential.
In
addition,
humans
of
all
ages
are
highly
exposed
to
them
from
natural
sources.
At
this
time,
there
is
no
concern
for
potential
sensitivity
to
infants
and
children.
A
safety
factor
analysis
has
not
been
used
to
assess
the
risk.
For
the
same
reasons
the
additional
tenfold
safety
factor
is
unnecessary.

4.
Fate
Assessment:

Biodegradation
of
propionic
acid
is
expected
to
be
the
most
important
degradation
pathway
in
aerobic
soil
and
water.
Data
indicate
that
propionic
acid
degrades
in
an
anaerobic
aquatic
system
with
a
half­
life
of
21
days.
Although
data
are
not
available,
EFED
expects
that
the
half­
life
in
aerobic
environments
will
be
much
lower
than
21
days
since
biodegradation
of
propionic
acid
occurs
rapidly
under
aerobic
conditions.
Based
on
an
estimated
K
oc
value
of
1.2
(
Syracuse
Research
Corporation,
SRC,
structure
estimation
method
using
molecular
connectivity
indices),
propionic
acid
is
expected
to
be
highly
mobile
in
soil.
Page
6
of
8
5.
Ecotoxicity
Assessment:

Aquatic
Organisms:
The
toxicity
data
indicate
that
propionic
acid
is
slightly
toxic
to
aquatic
organisms.
Toxicity
data
are
not
available
to
assess
chronic
risk
to
freshwater
organisms
or
acute
and
chronic
risks
to
estuarine/
marine
organisms.

Acute
Toxicity
of
Propionic
Acid
to
Freshwater
Aquatic
Organisms
(
based
on
application
rate
of
1
lb
ai/
A)

Organism
Exposure
Type
Most
Sensitive
Species
Toxicity
(
ppm)
EEC
(
ppm)
1
Risk
Quotient
(
EEC/
Toxicity)

Freshwater
Fish
Acute
Rainbow
trout
LC50=
51
0.06
<
0.05
Freshwater
Invertebrates
Acute
Daphnia
magna
EC50=
22.7
0.06
<
0.05
1
Maximum
EEC
generated
using
the
GENEEC
2.0
model.

Terrestrial
Organisms:
The
toxicity
data
indicate
that
propionic
acid
is
practically
non­
toxic
to
birds
and
mammals.
EFED
does
not
expect
risk
to
birds
and
mammals
on
an
acute
basis
at
application
rates

20.7
and

5.7
lb
ai/
A,
respectively.
Chronic
risks
to
terrestrial
organisms
could
not
be
determined
because
toxicity
data
are
not
available.

Acute
Toxicity
of
Propionic
Acid
to
Terrestrial
Wildlife
Animal
Group
Exposure
Type
Most
Sensitive
Species
Toxicity
(
mg/
kg)
EEC
(
ppm)
1
Risk
Quotient
Birds
Acute
Mallard
LD
50
>
10000
240
<
0.1
Mammals
Acute
Rat2
LD
50
=
2600
240
<
0.1
1
The
highest
terrestrial
residue
anticipated.
RQs
were
calculated
using
ELLFate
2
Accession
No.
091024
6.
Exposure
Assessments
Presentation
of
Dietary
(
food)
Exposure
Assessment:
Dietary
exposure
and
dietary
risk
to
propionic
acid
is
extremely
low.
A
dietary
risk
assessment
has
not
been
conducted
and
is
not
required.

Presentation
of
Drinking
Water
Exposure
Assessment:
As
with
most
acids,
propionic
acid
would
be
expected
to
be
mobile.
Biodegradation
should
be
rapid
under
aerobic
conditions.
Modeling
was
performed
to
estimate
the
possible
water
concentrations.
Page
7
of
8
Assumptions:
1
lb/
Acre
Modeling
Used:
FIRST,
SCIGROW
2
FIRST
TIER
I
Concentration
(
ppb)
of
propionic
acid
in
surface
water
Method
of
Application
Application
Rate
(
lbs
ai/
A)
Peak
(
Acute)
(
ppb)
Annual
Average
(
Chronic)
(
ppb)

Aerial
1
92
6
Groundwater
Screening
Concentrations
for
Propionic
Acid
using
SCIGROW
2
Application
Rate
(
lbs
ai/
A)
Groundwater
Screening
Concentration
(
ppb)
a
1
1.3
a
These
concentrations
are
the
screening
concentrations
for
acute,
chronic,
and
cancer
risks.

Given
the
lower
toxicity
profile
of
propionic
acid,
no
adverse
effects
as
a
result
of
exposure
through
drinking
water
are
expected
from
either
the
active
or
inert
ingredient
uses.
A
drinking
water
risk
assessment
is
not
required.

Currently
there
are
no
active
ingredient
registrations
for
residential
uses.
However,
the
potential
for
use
in
residential
products
as
an
inert
ingredient
does
exist.
Given
the
lower
toxicity
of
propionic
acid,
and
that
its
uses
generally
are
related
to
agricultural
and
dietary
(
food)
uses,
adverse
effects
as
a
result
of
any
residential
uses
are
not
expected.

7.
Cumulative
Exposure:

Section
408(
b)(
2)(
D)(
v)
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
EPA
does
not
have,
at
this
time,
data
available
to
determine
whether
propionic
acid
and
its
salts
have
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
this
pesticide
in
a
cumulative
risk
assessment.

8.
Summary
of
Exposure/
Risk
Characterization:

Based
on
its
low
toxicity,
and
affirmation
as
a
GRAS
chemical
when
used
as
a
direct
food
additive,
propionic
acid
is
not
expected
to
result
in
any
adverse
health
effects
via
the
food,
drinking
water,
or
residential
exposure
pathways.
Page
8
of
8
9.
Qualitative
Evaluation
of
Worker
Risks:

The
possibility
of
eye
and
skin
irritation
to
occupational
handlers
is
addressed
on
a
product­
specific
basis.

10.
IIFG
Recommendations:
By
consensus
there
were
no
objections
to
the
following:

°
The
petition
may
be
granted.
The
inert
and
active
uses
should
be
harmonized.

°
The
tolerance
exemptions
for
propionic
acid
under
40CFR
180.1001(
c)
and
180.1023
are
reassessed.

°
The
tolerance
exemption
for
sodium
propionate
under
40CFR
180.1001(
c)
is
reassessed.

°
A
tolerance
exemption
for
calcium
propionate
may
be
established.

°
Propionic
acid,
sodium
propionate
and
calcium
propionate
are
to
be
reclassified
as
List
4B.

Attachments:

(
1)
EFED
review
(
2)
HED
review