Document ID: EPA-HQ-OPP-2005-0487-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-01-25T05:00Z

Page
1
of
14
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
27,
2003
MEMORANDUM
FROM:
Kathryn
Boyle,
Chair
Lower
Toxicity
Pesticide
Chemical
Focus
Group
Registration
Division
TO:
Susan
Lewis,
Acting
Chief
Minor
Use,
Inerts,
and
Emergency
Response
Branch
Registration
Division
SUBJECT:
Recommendation
for
Tolerance
Reassessment
The
attached
science
assessment
discusses
the
toxicity
of
sorbic
acid
and
potassium
sorbate.
Based
on
their
long
history
of
use
as
a
food
additive
(
mold
inhibitor),
the
evaluations
by
the
Food
and
Drug
Administration
which
resulted
in
unlimited
GRAS
(
generally
recognized
as
safe)
determinations,
and
their
ready
metabolism,
a
qualitative
assessment
was
performed.

Based
on
its
review
and
evaluation
of
the
available
information,
EPA
concludes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
general
population,
and
to
infants
and
children
from
aggregate
exposure
to
residues
of
potassium
sorbate
and
sorbic
acid
from
their
uses
as
inert
ingredients
in
pesticide
products.
The
sorbic
acid
(
and
potassium
salt)
exemption
from
the
requirement
of
a
tolerance
as
established
in
40
CFR
180.1001
(
c)
is
reassessed.
The
entry
in
40
CFR180.2
(
which
counts
as
two
tolerance
exemptions)
is
also
reassessed.
Based
on
severe
dermal
irritation,
the
classification
of
sorbic
acid
as
List
4B
is
confirmed.
Based
on
its
use
in
FIFRA
25(
b)
deregulated
products
as
an
active
ingredient,
potassium
sorbate
is
reclassified
as
List
4A
for
harmonization.
Page
2
of
14
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
24,
2003
Memorandum
Subject:
Sorbic
Acid
and
Its
Potassium
Salt:
Science
Assessment
Document
for
Tolerance
Reassessment.

CAS
No.:
Sorbic
Acid:
110­
44­
1
Potassium
Sorbate:
590­
00­
1;
24634­
61­
5
Chemical
Class:
unsaturated
aliphatic
acid
and
its
potassium
salt
40
CFR:
180.1001
(
c)

From:
Bentley
C.
Gregg,
Risk
Assessor
Product
Reregistration
Branch
Special
Review
and
Reregistration
Division
(
7508C)

Through:
Linda
Propst,
Branch
Chief
Mark
Perry,
Team
Leader
Product
Reregistration
Branch
Special
Review
and
Reregistration
Division
(
7508C)

To:
Lower
Toxicity
Pesticide
Chemical
Focus
Group
Kathryn
Boyle,
Chair
Registration
Division
(
7505C)

Background:

Attached
is
the
Lower
Toxicity
Pesticide
Chemical
Focus
Group's
science
assessment
for
sorbic
acid
and
its
potassium
salt.
This
assessment
summarizes
available
information
on
the
uses,
physical/
chemical
properties,
toxicological
effects,
exposure
profile,
and
environmental
fate
and
ecotoxicity
of
these
substances.
In
performing
this
assessment,
EPA
has
relied
on
peer­
reviewed
evaluations
performed
by
the
Food
and
Drug
Administration
(
FDA),
and
the
Food
and
Page
3
of
14
Agriculture
Organization
of
the
World
Health
Organization
(
FAO/
WHO).

I.
Executive
Summary:

Sorbic
acid
is
an
unsaturated
aliphatic
acid,
a
straight
chain
of
6
carbons
with
double
bonds
at
the
2
and
4
positions
and
a
terminal
carboxylic
acid
group
(
i.
e.,
at
the
1
position).
The
potassium
salt
is
formed
by
mixing
sorbic
acid
with
potassium
hydroxide
to
form
the
potassium
sorbate.
Both
sorbic
acid
and
potassium
sorbate
have
been
classified
by
the
U.
S.
Food
and
Drug
Administration
(
FDA,
1975)
as
Generally
Recognized
as
Safe
(
GRAS).
Innumerable
tons
of
foodstuffs
are
saved
from
perishing
each
year
because
of
the
use
of
sorbic
acid
and/
or
potassium
sorbate
as
a
preservative
method.
They
protect
the
food
products
from
attack
by
mold,
yeast
and
bacteria.
They
inhibit
mold
from
growing,
although
they
do
not
kill
already
established
mold.

Potassium
sorbate
is
highly
water
soluble,
and
although
sorbic
acid
is
soluble
in
fats,
oils,
and
some
solvents,
the
acid
has
a
water
solubility
of
about
2000
mg/
L,
so
it
is
soluble
in
water
at
the
concentrations
likely
to
enter
water,
and
it
will
exist
in
its
dissociated
state
within
the
range
of
environmentally
relevant
pHs.
Both
sorbic
acid
and
potassium
sorbate
are
readily
biodegraded
and
are
predicted
to
be
relatively
non­
toxic
to
aquatic
species.

Open
literature
studies
and
information
from
various
internet
websites
show
that
there
are
a
number
of
toxicological
studies
with
sorbic
acid,
and
some
with
potassium
sorbate,
with
the
data
indicating
that
these
two
substances
do
not
pose
serious
health
effects
from
exposure.
Sorbic
acid
is
rapidly
metabolized,
with
85%
of
the
radiolabeled
dose
found
in
the
expired
CO
2
in
both
the
rat
and
mouse.

A
WHO
Joint
Expert
Committee
on
Food
Additives
Committee
has
concluded
that
both
sorbic
acid
and
potassium
sorbate
are
readily
metabolized
and
that
both
rats
and
humans
appear
to
utilize
identical
metabolic
mechanisms;
that
they
did
not
cause
tumors
when
administered
orally
and
produced
no
evidence
of
carcinogenic
potential;
that
the
level
causing
no
toxicological
effect
in
the
rat
was
50,000
ppm
(
5%)
in
the
diet,
which
is
equivalent
to
2500
mg/
kg
bw/
day;
and
the
estimate
of
acceptable
daily
intake
in
humans
was
0
to
25
mg/
kg
bw,
expressed
in
units
as
the
sum
of
sorbic
acid
and
potassium
sorbate,
as
well
as
the
calcium
and
potassium
sorbates
(
with
the
salts
calculated
as
sorbic
acid).

Based
on
available
information
on
sorbic
acid
and
its
potassium
salt,
their
expected
use
patterns,
their
GRAS
status
and
safe
history
of
use
as
food
additives,
and
extensive
uses
as
preservatives
in
commercially­
available,
over­
the­
counter
foods,
the
Lower
Toxicity
Pesticide
Chemical
Focus
Group
has
determined
that
a
screening
level
quantitative
risk
assessment
is
not
required
for
these
substances.

II.
Use
Information:

The
pesticidal
and
non­
pesticidal
uses
of
sorbic
acid
and
its
potassium
salt
are
summarized
Page
4
of
14
briefly
below.

Table
1.
Use
Pattern
(
pesticidal
ingredient)

Chemical
Name
PC
Code
40
CFR
Use
Pattern
(
Pesticidal)
Current
Inert
List
"
Sorbic
acid
(
and
potassium
salt)"
acid:
875901
salt:
875902
180.1001
(
c)
Preservative
for
formulations
acid:
4B
salt:
4B
Potassium
sorbate
075902
180.2
­­­
­­­

Sorbic
acid
also
has
an
active
ingredient
PC
Codes:
075901.

Use
Pattern
(
non­
pesticidal):

Sorbic
acid
is
generally
recognized
as
safe
(
GRAS)
by
the
U.
S.
FDA
when
used
in
accordance
with
good
manufacturing
practice
(
21
CFR
182.3089);
therefore,
the
only
limitation
on
its
use
is
that
the
quantity
not
exceed
the
amount
reasonably
required
to
accomplish
the
desired
preservative
function.
Sorbic
acid
is
used
for
the
following:
as
a
mold
and
yeast
inhibitor;
as
a
fungistatic
agent
for
foods,
especially
cheeses;
to
improve
the
characteristics
of
drying
oils;
in
alkyd
type
coatings
to
improve
gloss;
and
to
improve
the
milling
characteristics
of
cold
rubber.

Potassium
sorbate
is
also
generally
recognized
as
safe
by
FDA
when
used
in
accordance
with
good
manufacturing
practice,
without
any
other
specified
limitation
(
21
CFR
182.3640),
and
is
also
listed
as
GRAS
when
migrating
to
food
from
paper
and
paperboard
products
used
in
food
packaging
(
21
CFR
182.90).
Potassium
sorbate
is
used
as
a
mold
and
yeast
inhibitor.
It
is
also
used
as
a
chemical
preservative
food
additive
and
an
antioxidant
in
food.

Innumerable
tons
of
foodstuffs
are
saved
from
perishing
each
year
because
of
the
use
of
sorbic
acid
and/
or
potassium
sorbate
as
a
preservative
method.
They
protect
the
food
products
from
attack
by
mold,
yeast
and
bacteria.
They
inhibit
mold
from
growing,
although
they
do
not
kill
already
established
mold.

III.
Physical/
Chemical
Properties:

The
actual
chemical
name
for
the
substance
known
by
the
common
name
Sorbic
Acid
is
trans,
trans­
2,4­
hexadienoic
acid
(
or
E,
E­
2,4­
hexadienoic
acid).
It
is
a
straight
chain
(
aliphatic),
unsaturated
(
double
bonds
at
the
2
and
4
positions)
acid,
with
both
the
double
bonds
being
in
the
trans
configuration,
and
a
terminal
(
at
the
1­
position)
carboxylic
acid.
Sorbic
acid
is
produced
by
the
trimerization
of
acetaldehyde
and
the
catalytic
air
oxidation
of
the
resulting
2,4­
hexadienal.

Potassium
sorbate
is
the
potassium
salt
of
sorbic
acid.
It
is
produced
by
mixing
equimolar
Page
5
of
14
amounts
of
sorbic
acid
and
potassium
hydroxide.

Sorbic
acid
has
been
characterized
as
an
unsaturated
fatty
acid
which
has
two
double
bonds
in
conjugation
(
that
is,
two
double
bonds
separated
only
by
one
single
bond).
Potassium
sorbate
is
highly
water
soluble.
Sorbic
acid
is
highly
soluble
in
fats,
oils,
and
some
solvents,
and
is
soluble
in
water
at
1900
mg/
L,
so
it
is
soluble
at
most
concentrations
likely
to
enter
water.
The
acid
it
will
exist
in
its
dissociated
state
within
the
range
of
environmentally
relevant
pHs
Table
2.
Physical/
Chemical
Properties
(
from
HSDB,
unless
specified).

Sorbic
acid
Potassium
sorbate
Molecular
formula
C
6
H
8
O
2
C
6
H
7
O
2
°
K
Molecular
weight
112.13
150.22
Melting
point
134.5
°
C
270
°
C
Solubility
in
water
1,910
mg/
L
at
30
°
C
585,000
mg/
L
at
25
°
C
pH
­­
­­

Density/
Specific
Gravity
1.204
@
19
°
C
/
4
°
C
1.363
@
25
°
C
/
20
°
C
Vapor
Density
3.87
­­

Octanol/
Water
Partition
Coefficient
log
K
ow
=
1.33
­­

Physical
state
colorless
needles
or
white
powder
White
crystals
or
powder
Dissociation
Constant
1.73
x
10­
5
@
25
°
C;
pKa
=
4.76
Estimated
Vapor
Pressure
9.9
x
10­
3
mm
Hg
@
25
°
C;
50
mm
Hg
@
143
°
C
­­

Henry's
Law
constant
5.0
x
10­
8
atm­
m3/
mole
­­

Soil
Sorption
Coefficient
K
oc
=
130
­­

Bioconcentration
Factor
6.0
­­

Environmental
Biodegradation
as
a
simple
unsaturated
fatty
acid,
sorbic
acid
should
be
readily
biodegraded
in
the
environment
(
similar
to
the
acid)
Page
6
of
14
Environmental
Abiotic
Degradation
sorbic
acid
is
not
expected
to
undergo
hydrolysis
in
the
environment
due
to
a
lack
of
hydrolyzable
functional
groups,
but
will
directly
photolyze
rapidly
due
to
reaction
with
hydroxyl
radicles
and
ozone
in
the
atmosphere
(
similar
to
the
acid)

IV.
Hazard
Assessment:

Toxicological
Profile:

Table
3.
Summary
of
Acute
Toxicity
Data
on
Sorbic
Acid
and
Potassium
Sorbate.

Sorbic
Acid
Potassium
Sorbate
Test
Species
Results
Category
Species
Results
Category
Oral
LD50
rat
7360­
10,500
mg/
kg
IV
rat
4340
­
4920
mg/
kg
III
Dermal
LD50
rabbit
>
10,000
mg/
kg
IV
no
data
Inhalation
LC50
no
data
no
data
Eye
Irritation
rabbit
no
data
humans
"
can
cause
irritation"
NA
Dermal
Irritation
rabbit
severe
I
humans
"
contact
dermatitis"
NA
Dermal
Sensitization
no
data
no
data
Sorbic
Acid.
The
acute
oral
LD
50
values
for
sorbic
acid
in
the
rat
have
been
reported
to
be
7360,
7400,
and
10,500
mg/
kg,
and
3200
mg/
kg
in
the
mouse.
The
acute
dermal
toxicity
to
the
rabbit
has
been
reported
as
>
1000
mg/
kg,
from
a
limit
dose
test.
Sorbic
acid
has
exhibited
severe
irritation
when
administered
to
the
skin
of
humans
(
150
mg
for
1
hour)
and
severe
irritation
when
administered
to
the
skin
of
the
rabbit
(
1
mg).
In
another
study,
sorbic
acid
was
reported
to
be
a
primary
irritant
to
human
skin
when
applied
at
0.15%
concentration
in
water
under
conditions
of
a
closed
patch
test,
while,
in
another
study,
sorbic
acid
did
not
show
any
primary
irritation
or
sensitization
of
guinea
pig
skin
when
two
samples
were
applied
at
0.1
molar
concentration.
In
mutagenicity
testing,
sorbic
acid
was
found
to
be
negative
in
sister
chromatid
exchange
studies
with
Chinese
hamster
cells
from
the
lung,
tested
at
doses
up
to
1050
µ
g/
mL
(
mg/
L).
Page
7
of
14
The
World
Health
Organization
(
WHO)
Joint
Expert
Committee
on
Food
Additives
monograph
(
1967)
reported
results
from
a
study
in
which
radiolabeled
sorbic
acid
was
administered
to
the
rat
and
its
subsequent
metabolism
was
evaluated
(
Fingerhut
et
al.
1962,
as
cited
in
WHO
1967).
The
monograph
reported
that
85%
of
the
labeled
carbon
activity
was
found
in
the
expired
CO
2
,
while
0.4%
was
found
in
the
feces,
2%
in
the
urine
as
urea
and
CO
2
,
3%
in
internal
organs,
3%
in
the
skeletal
muscles,
and
6.6%
in
the
other
parts
of
the
carcass.
No
glycogen
was
formed
from
the
sorbic
acid.
Most
of
the
radiolabeled
activity
was
found
in
the
subcutaneous
fat
deposits
and
in
the
lipids
of
the
organs.
There
was
a
linear
relationship
between
dose
and
oxidation
rate;
the
half­
life
of
the
oxidation
was
reported
to
be
40­
110
minutes
in
the
dose
range
from
60­
1200
mg/
kg
body­
weight.
The
WHO
monograph
also
reported
a
similar
experiment
on
mice,
also
using
radiolabeled
sorbic
acid
(
Westöö,
1964,
as
cited
in
WHO
1967),
and
the
results
in
the
rat
were
confirmed
in
the
mouse;
in
these
mouse,
81%
±
10%
of
the
sorbic
acid
was
oxidized
to
CO
2
,
with
the
dose
given
ranging
from
40­
3000
mg/
kg
body­
weight.
About
7%
of
the
activity
was
excreted
as
sorbic
acid,
and
0.4%
as
trans,
trans­
muconic
acid.

The
WHO
monograph
(
1967)
also
described
results
from
a
long­
term
feeding
experiment
in
which
groups
of
100
rats
(
50
males
and
50
females)
were
given
0
and
5%
sorbic
acid
for
the
entire
life­
span
of
the
first
generation.
The
average
life­
span
of
the
group
fed
sorbic
acid
was
811
days
for
the
males
and
789
days
for
the
females,
while
the
life­
span
of
the
control
group
males
was
709
days
and
804
days
for
the
females,
with
the
monograph
indicating
"
possibly
suggesting
protection
by
sorbic
acid
against
lung
infection."
Autopsies
were
performed
on
all
the
rats
of
the
first
generation
that
died
during
the
experiment,
and
there
were
no
differences
in
the
organ
weight
of
the
individual
groups
nor
in
the
distribution
of
the
causes
of
death.
In
each
group
(
5%
sorbic
acid
and
controls),
only
2
tumors
were
found.
Animals
of
the
second
generation
were
sacrificed
after
250
days
of
feeding
sorbic
acid,
and
examination
of
liver,
kidney,
heart,
and
testes
showed
no
abnormalities.

A
subsequent
WHO
monograph
(
1974)
reported
that
sorbic
acid
did
not
act
as
an
antimetabolite
for
the
essential
fatty
acids
in
the
rat,
and
the
incorporation
of
sorbic
acid
in
the
diet
of
the
rats
did
not
cause
a
decrease
in
the
efficiency
of
their
utilization
of
calories.
The
sorbic
acid
was
utilized
as
a
source
of
calories,
and
was
reported
to
be
metabolized
similarly
to
caproic
acid.
The
monograph
also
reported
the
results
of
a
multi­
generation
feeding
study
in
the
rat.
Both
male
and
female
rats
were
fed
a
diet
containing
either
0%
or
10%
sorbic
acid
for
120
days,
and
after
60
days,
rats
in
each
group
were
mated,
and
each
group
produced
similar
numbers
of
offspring.
Then
rats
in
the
next
generation
(
F1)
were
fed
control
diet
or
that
containing
10%
sorbic
acid,
and
mated
after
70
days,
and
again,
similar
numbers
of
offspring
were
produced
(
the
F2
generation).
It
was
reported
that
the
females
in
the
10%
sorbic
acid
group
exhibited
normal
liver
weights,
relative
to
the
controls,
but
that
the
males
exhibited
reduced
growth.

In
another
study
reviewed
in
the
WHO
(
1974)
monograph,
groups
of
male
and
female
mice
were
dosed
by
oral
intubation,
receiving
40
mg/
kg/
day
of
sorbic
acid
for
two
months.
There
were
no
differences
observed
in
survival,
weight
gain,
or
food
consumption
between
the
treatment
and
control
groups.
At
the
end
of
this
dosing
period,
food
was
restricted
by
50%
for
5
days,
and
in
the
group
previously
dosed
with
sorbic
acid,
the
mortality
and
weight
loss
were
less
than
in
the
Page
8
of
14
control
group.
In
a
similar
oral
intubation
study
at
80
mg/
kg/
day
for
three
months,
the
growth
in
the
sorbic
acid
dosed
group
was
somewhat
lower
than
the
control
group.
The
subsequent
food
restriction
period
in
this
part
of
the
study
was
90%
food
restriction
for
18
days,
with
no
difference
in
mortality
of
the
mice
between
the
controls
and
the
group
previously
dosed
with
sorbic
acid.

The
later
WHO
monograph
(
1974)
also
described
various
short­
term
feeding
studies.
In
one
study,
rats
fed
sorbic
acid
in
the
diet
at
1%
or
2%
for
80
days
were
found
to
have
no
adverse
effects
of
growth
nor
any
histological
abnormalities
in
any
of
the
internal
organs
examined,
although
the
livers
were
slightly
larger
than
in
the
control
group.
In
another
study,
rats
were
fed
1%
or
10%
sorbic
acid
in
the
diet
for
four
months,
and
the
1%
group
showed
no
effect
on
blood
cholesterol
levels,
while
there
was
an
increase
in
cholesterol
in
the
10%
group,
as
well
as
fat
deposition
in
the
internal
organs.
In
addition,
there
was
a
decrease
in
the
number
of
leucocytes
and
some
impairment
of
cholinesterase
activity
after
two
months.
Groups
of
male
and
female
rats
were
administered
diets
of
0%
or
10%
sorbic
acid
for
120
days,
and
gross
appearance,
behavior,
and
food
consumption
were
similar
between
groups,
but
some
of
the
10%
sorbic
acid
dosed
rats
exhibited
increased
liver
to
body
weight
ratios.
In
another
study,
tests
were
conducted
in
two
different
laboratories
with
two
different
strains
of
rats
fed
diets
containing
4%
or
8%
sorbic
acid
for
90
days,
and
there
were
no
effects
on
the
rate
of
weight
gain,
and
the
rats
in
the
4%
group
showed
no
abnormalities
in
renal,
hepatic
or
other
tissues.
However,
the
rats
in
the
8%
group
showed
a
slight
but
statistically
significant
increase
in
relative
liver
weights,
while
the
histopathological
appearances
of
the
livers
were
normal.
In
another
feeding
study,
in
the
rabbit,
a
dosage
of
3.3
g/
kg
bw/
day
of
sorbic
acid
was
tolerated
without
any
adverse
effects.
In
another
study,
groups
of
dogs
received
a
diet
of
50%
cheddar
cheese
for
3
months,
with
one
group
receiving
cheese
with
4%
sorbic
acid
added,
a
second
group
with
4%
caproic
acid
added,
and
the
control
group
without
added
preservative;
the
responses
observed
were
similar
among
all
three
groups,
and
there
were
no
histopathological
differences
observed
in
the
tissues
among
any
of
the
three
groups
of
dogs.

Sorbic
acid
was
administered
to
rats
in
the
drinking
water
at
"
10
mg/
100
mL"
(
i.
e.,
100
mg/
L)
for
64
weeks,
and
the
rats
observed
for
tumors,
and
the
WHO
monograph
(
1973)
reported
the
dosing
failed
to
produce
any
tumors.
In
another
study,
groups
of
male
and
female
mice
were
administered
40
mg/
kg/
day
of
sorbic
acid
in
the
diet
(
total
dosing
period
not
reported),
and
there
were
no
tumors
observed
in
either
the
dosed
or
control
group.
In
addition,
the
general
condition,
behavior,
weight
gain,
and
survival
were
similar
among
the
mice
in
the
dosed
and
control
group,
but
the
sorbic
acid­
dosed
group
exhibited
lower
relative
weights
for
the
liver,
kidney,
and
testes.

The
WHO
monograph
(
1973)
also
reported
the
results
of
long­
term
dosing
studies.
Male
and
female
rats
received
a
diet
containing
sorbic
acid
at
40
mg/
kg/
day
for
18
months.
At
the
end
of
this
dosing
period,
food
was
completely
withheld
from
the
rats
for
13
days,
and
the
test
group
showed
higher
survival
than
the
control
group.
The
blood
pH,
C­
reactive
protein
levels,
and
blood
morphology
were
similar
between
the
test
group
and
the
controls,
and
there
were
no
significant
differences
in
either
the
serum
ceruloplasmin,
serum
complement,
or
phagocytic
activity
of
the
leucocytes.
The
WHO
monograph
reported
that
weight
gain
was
not
measured
during
the
18­
month
dosing
period,
nor
were
any
results
reported
for
tumors.
In
another
study
Page
9
of
14
reviewed,
sorbic
acid
was
fed
to
rats
at
5%
in
the
diet
for
1000
days,
over
two
generations,
with
no
adverse
effects
of
weight
gain
or
reproduction,
and
"
no
ill
effects
were
observed,"
and
no
sorbic
acid
was
found
in
the
urine
of
the
dosed
rats.
Based
on
these
various
studies,
the
WHO
Committee
(
1973)
concluded
the
following:
sorbic
acid
is
readily
metabolized;
both
rats
and
humans
appear
to
utilize
identical
metabolic
mechanisms
for
the
oxidation
of
sorbate;
sorbic
acid
did
no
cause
tumors
when
administered
orally
and
produced
no
evidence
of
carcinogenic
potential;
the
level
causing
no
toxicological
effect
in
the
rat
was
50,000
ppm
(
5%)
in
the
diet,
which
is
equivalent
to
2500
mg/
kg
bw/
day;
and
the
estimate
of
the
acceptable
daily
intake
in
humans
was
0
to
25
mg/
kg
bw.

Additional
more­
recent
information
is
also
presented
in
the
HSDB
of
TOXNET
regarding
the
studies
to
assess
the
effects
of
sorbic
acid.
Daily
doses
to
the
rat
of
about
50
mg/
kg
in
food
for
30
days
were
reported
to
have
"
caused
some
reduced
growth"
(
only
information
reported
in
HSDB).
No
adverse
effects
were
reported
in
the
blood
or
internal
organs
of
rats,
guinea
pigs,
rabbits
or
dogs
after
"
prolonged
feeding"
at
1
to
500
times
the
mount
of
sorbic
acid
used
in
foods.
Sorbic
acid
fed
to
male
and
female
mice
at
dietary
levels
of
0,
1,
5,
or
10%
for
80
weeks,
and
fed
to
male
and
female
rats
at
0,
1,
5,
or
10%
for
2
years,
were
reported
to
have
caused
no
increases
in
the
numbers
of
deaths
or
in
the
incidence
of
spontaneous
histological
lesions,
including
tumors.
In
another
study,
tumors
were
not
observed
in
male
or
female
rats
fed
a
diet
containing
sorbic
acid
at
40
mg/
kg/
day
for
18
months,
or
in
male
or
female
mice
also
administered
40
mg/
kg/
day
for
17
months.
It
was
also
reported
that
in
rats,
the
metabolism
of
sorbic
acid
is
identical
with
that
of
normally
occurring
fatty
acids,
and
that
under
normal
conditions
of
ingestion,
sorbic
acid
is
completely
oxidized
to
carbon
dioxide
and
water.
This
metabolism
of
sorbic
acid
is
by
the
betaoxidation
route
to
carbon
dioxide,
but
that
traces
(
0.1%
of
the
dose)
are
converted
into
trans,
trans­
muconic
acid.

In
another
study
reviewed
in
TOXNET,
mice
were
fed
a
diet
containing
15%
sorbic
acid
for
88
weeks,
and
developed
a
high
incidence
of
hepatoma.
The
glutathione
levels
in
the
livers
of
the
mice
administered
at
15%
were
found
to
be
decreased
to
40%
of
the
amount
reported
in
the
controls
after
a
3­
month
feeding
period,
with
the
decreased
level
continuing
until
the
end
of
the
experiment
after
12
months,
with
a
close
correlation
observed
between
the
extent
of
the
depletion
of
the
glutathione
levels
in
the
livers
and
the
concentrations
of
sorbic
acid
in
the
diet.
It
was
also
reported
that
in
this
same
strain
of
mice
fed
a
diet
containing
15%
sorbic
acid
for
up
to
6
months,
the
acidic
fraction
of
an
ether
extract
was
found
to
exhibit
a
slight
mutagenic
activity
in
an
Ames
test
(
with
Salmonella
typhimurium
TA
98
in
the
presence
of
a
liver
9000­
g
supernatant);
therefore,
it
had
been
inferred
that
the
hepatomas
which
developed
in
the
mice
dosed
at
15%
may
have
been
induced
by
both
the
chronic
depletion
of
the
hepatic
glutathione
and
by
the
gradual
production
of
these
promutagens
in
the
mice
intestine
which
were
then
absorbed
and
metabolically
activated
by
the
liver.
(
Since
its
use
in
food
is
as
a
preservative,
sorbic
acid
at
15%
of
the
total
diet
would
appear
to
represent
an
unusually
elevated
level
for
human
dietary
ingestion,
since
TOXNET
indicates
that
the
highest
level
of
potassium
sorbate
is
in
regular
cheese,
at
0.3%,
except
for
the
single
exception
of
dipping
the
sausage
casings
in
a
2.5%
solution,
before
stuffing
with
meat.)
Page
10
of
14
Potassium
Sorbate.
The
acute
oral
LD
50
values
for
potassium
sorbate
have
been
reported
to
be
4340
mg/
kg
and
4920
mg/
kg
in
the
rat,
and
3800
mg/
kg
in
the
mouse.
Potassium
sorbate
has
been
reported
to
cause
aged,
contact
dermatitis
and
can
cause
eye
irritation.
Two
mutagenicity
tests
have
been
reported
with
potassium
sorbate;
it
did
induce
chromosomal
aberrations
in
cultured
Chinese
hamster
fibroblast
cells
(
at
doses
up
to
4
g/
L
for
48
hours),
but
the
results
from
sister
chromatid
exchange
studies
with
Chinese
hamster
cells
from
the
lung
were
found
to
be
not
conclusive
(
at
doses
up
to
10
g/
L).

The
World
Health
Organization
(
WHO)
Joint
Expert
Committee
on
Food
Additives
monograph
(
1967)
reported
results
from
a
feeding
study
in
which
groups
of
male
and
female
rats
were
fed
potassium
sorbate
(
solid
or
mixed
isomers)
at
levels
of
0,
1,
2,
5,
or
10%
in
the
diet
for
3
months.
The
body
weight
gain
in
the
group
fed
10%
potassium
sorbate
was
initially
depressed,
and
was
also
to
a
lesser
degree
in
the
group
fed
5%;
however,
there
were
no
data
reported
for
food
consumption
during
this
initial
feeding
period.
At
the
conclusion
of
the
entire
3­
month
dosing
period,
the
overall
body
weights
of
the
rats
receiving
this
highest
dose
of
potassium
sorbate
(
10%)
were
"
slightly
depressed,"
but
data
also
indicated
that
food
consumption
was
lower
in
this
group;
thus,
it
was
also
observed
that
food
efficiency
(
reported
as
weight
gain
per
gram
of
food
ingested)
for
this
10%
group
was
similar
to
that
in
the
controls.
The
relative
liver
weights
were
the
same
in
all
dosing
groups,
but
the
kidney
weights
were
greater
in
the
10%
group,
and
to
a
lesser
extent
in
the
5%
group,
which
was
"
probably
due
to
the
high
potassium
load."
Gross
pathological
examinations
revealed
no
abnormalities,
even
in
the
highest
dose
group.

The
WHO
monograph
(
1967)
also
reported
a
study
in
which
dogs
were
administered
1
or
2%
potassium
sorbate
(
as
solid
or
mixed
isomers)
in
the
diet
for
3
months.
There
were
no
differences
between
either
of
the
dosed
groups
and
the
controls
for
weight
gain,
and
gross
examination
on
autopsy
showed
no
indications
of
any
deleterious
effects
attributable
to
the
sorbates.
Based
on
these
results,
the
WHO
Committee
concluded
that
10%
potassium
sorbate,
and
even
somewhat
lower
levels,
result
in
a
very
high
intake
of
potassium,
with
the
consumption
of
food
at
15
grams/
rat/
day
resulting
in
a
daily
intake
of
12
meq
of
potassium
for
the
10%
dose
group,
whereas
the
normal
daily
intake
of
potassium
for
the
mature
rat
is
1.5
meq
of
potassium.
The
WHO
Committee
report
concluded
with
an
Evaluation
that
the
level
causing
no
toxicological
effect
in
the
rat
was
50,000
ppm
in
the
diet,
which
is
equivalent
2,500
mg/
kg
body­
weight/
day,
and
that
the
Estimate
of
acceptable
daily
intakes
for
man
would
be
as
follows:
Unconditional
Acceptance:
0
to
12.5
mg/
kg
body­
weight;
and
Conditional
Acceptance:
12.5
to
25
mg/
kg
bodyweight
in
units
as
the
sum
of
sorbic
acid
and
potassium
sorbate,
as
well
as
the
calcium
and
potassium
sorbates
(
calculated
as
sorbic
acid).

In
a
subsequent
WHO
monograph
(
1973),
results
were
reported
concerning
a
study
in
which
potassium
sorbate
was
administered
in
either
the
drinking
water,
at
0.3%,
or
in
the
diet,
at
0.1%,
for
100
weeks.
Survival
and
general
conditions
of
the
rats
were
satisfactory.
No
special
features
were
seen
at
65
weeks
in
laparotomy
(
surgical
incision
into
the
abdominal
wall),
nor
at
100
weeks,
when
all
the
animals
had
died.
In
the
carcinogenicity
aspect
of
this
study,
it
was
reported
that
these
dosing
regimes
failed
to
produce
any
tumors.
Based
on
these
various
studies,
the
WHO
Committee
(
1973)
concluded
the
following:
sorbic
acid
is
readily
metabolized;
both
rats
Page
11
of
14
and
humans
appear
to
utilize
identical
metabolic
mechanisms
for
the
oxidation
of
sorbate;
longterm
feeding
studies
suggest
that
the
same
no­
effect
level
applies
to
the
salts
as
to
the
free
acid;
potassium
sorbate
did
no
cause
tumors
when
administered
orally
and
produced
no
evidence
of
carcinogenic
potential;
the
level
causing
no
toxicological
effect
in
the
rat
was
50,000
ppm
(
5%)
in
the
diet,
which
is
equivalent
to
2500
mg/
kg
bw/
day;
and
the
estimate
of
acceptable
daily
intake
in
humans
was
0
to
25
mg/
kg
bw,
reported
in
units
as
the
sum
of
sorbic
acid
and
potassium
sorbate,
as
well
as
calcium
and
sodium
sorbate
(
these
salts
expressed
as
sorbic
acid).

Risk
Characterization:
Taking
into
consideration
all
available
information
on
sorbic
acid
and
its
potassium
salt,
including
their
designations
by
FDA
as
GRAS,
the
information
compiled
on
them
in
WHO/
FAO
monographs
and
TOXNET,
as
well
as
their
presence
as
preservatives
in
foods,
it
is
concluded
that
the
uses
of
sorbic
acid
and
potassium
sorbate
as
inert
ingredients
in
pesticide
products
are
unlikely
to
pose
a
significant
hazard
to
the
general
public
or
any
population
subgroup.
Sorbic
acid
and
potassium
sorbate
are
readily
metabolized,
and
in
long­
term
feeding
studies,
showed
no
adverse
effects
and
produced
no
evidence
of
carcinogenic
potential,
with
no
toxicological
effects
observed
in
the
rat
at
50,000
ppm
(
5%)
in
the
diet,
which
is
equivalent
to
2500
mg/
kg
bw/
day,
so
the
WHO
estimate
of
acceptable
daily
intake
in
humans
was
0
to
25
mg/
kg
bw,
reported
in
units
as
the
sum
of
sorbic
acid
and
potassium
sorbate,
as
well
as
calcium
and
sodium
sorbate
(
these
salts
expressed
as
sorbic
acid).
As
a
result,
OPP
is
recommending
a
qualitative
approach
to
assessing
human
health
risks
from
exposure
to
sorbic
acid
and
its
potassium
salt.

Special
Considerations
for
Infants
and
Children:
At
this
time,
there
is
no
concern
for
sorbic
acid
or
potassium
sorbate
to
have
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.

V.
Exposure
Assessment:

Exposure
to
both
sorbic
acid
and
its
potassium
salt,
potassium
sorbate,
may
occur
through
their
FDA­
approved
GRAS
uses
as
food
additives
for
preservative
purposes.
Based
on
the
extensive
use
of
sorbic
acid
and
potassium
sorbate
in
many
types
of
foods
(
approved
FDA
uses),
the
potential
exposures
to
these
substances
as
a
result
of
use
in
pesticide
products
are
expected
to
be
minimal.
Therefore,
a
screening
level
quantitative
exposure
assessment
has
not
been
conducted.

VI.
Environmental
Fate/
Ecotoxicity/
Drinking
Water
Considerations:

HSDB
in
TOXNET
discusses
the
environmental
fate
of
sorbic
acid.
In
addition,
information
from
HSDB
has
been
supplemented
with
predictive
modeling,
based
on
structure
activity
relationships.
Potassium
sorbate
is
highly
water
soluble,
and
thus
readily
dissociates
into
its
anion
(
the
dissociated
sorbic
acid)
and
its
cation
(
the
potassium
ion).
Thus,
the
environmental
Page
12
of
14
fate
and
effects
of
potassium
sorbate
are
closely
related
to
sorbic
acid
and
the
free
potassium
ion.

Based
on
their
low
K
oc
(
i.
e.,
less
than
10
L/
g)
and
low
K
ow
(
i.
e.,
about
1.3
for
sorbic
acid
and
2.2
for
the
sorbate
salts)
values,
sorbic
acid
and
its
salts
are
classified
as
highly
mobile
in
soil
(
McCall
et
al.
[
undated]).
Volatilization
from
moist
soil
surfaces
would
not
be
expected
to
be
an
important
fate
process,
based
on
the
low
Henry's
Law
constant
values
for
both
the
acid
and
its
salts,
but
sorbic
acid
has
the
potential
to
volatilize
from
dry
soil
surfaces,
based
on
its
vapor
pressure
of
about
1
x
10­
2
mm
Hg,
but
the
volatility
of
the
dissociated
acid
(
anion)
would
be
minimal.
As
a
simple
unsaturated
aliphatic
(
fatty)
acid,
sorbic
acid
would
be
expected
to
be
readily
biodegraded
in
the
environment,
and
has
been
observed
to
degrade
in
soil
suspension.
Overall
half­
lives
in
acclimated
systems
would
range
from
hours
to
days
for
primary
degradation,
and
days
to
weeks
for
ultimate
degradation
(
mineralization),
based
on
the
ready
biodegradability
model
(
Meylan
and
Howard,
2000).
Due
to
the
lack
of
hydrolyzable
functional
groups,
abiotic
degradation
of
sorbic
acid
in
the
soil
would
not
be
expected
to
be
an
important
fate
process.

Sorbic
acid
is
soluble
in
water
at
about
2000
mg/
L,
and
its
anion
(
dissociated
acid)
and
the
potassium
ion
are
miscible
in
water.
Based
on
their
K
oc
and
K
ow
values,
sorbic
acid
and
the
sorbate
salts
would
not
be
expected
to
adsorb
to
suspended
solids
or
sediments
in
water.
Volatilization
from
water
would
not
be
expected
to
be
an
major
fate
process
for
sorbic
acid,
based
on
its
Henry's
Law
constant.
The
dissociation
constant
for
sorbic
acid
(
pKa
of
4.76)
suggests
that
in
the
range
of
environmentally
relevant
pHs,
it
would
exist
in
a
dissociated
state
(
as
its
cation
[
the
hydrogen
ion]
and
its
anion
[
the
negatively­
charged,
dissociated
sorbate
moiety]).
Based
on
its
low
K
ow
and
low
estimated
Bioconcentration
Factor
values,
there
is
a
low
potential
for
bioconcentration
in
aquatic
animals.
Sorbic
acid
in
water
is
expected
to
be
very
readily
biodegraded,
by
both
aerobic
and
anaerobic
bacteria,
while
its
abiotic
degradation
in
water
would
be
a
very
minor
pathway
of
breakdown.

If
any
sorbic
acid
should
enter
the
atmospheric
compartment
of
the
environment,
it
is
expected
to
exist
solely
as
a
vapor.
Vapor­
phase
sorbic
acid
would
be
readily
degraded
in
the
atmosphere
by
reactions
with
either
or
both
photochemically­
produced
hydroxyl
radicles
and
ozone,
with
estimated
half­
life
values
on
the
order
of
hours,
both
with
hydroxyl
radicles
and
with
the
vapor­
phase
reaction
between
sorbic
acid
and
ozone.

Sorbic
acid
is
relatively
non­
toxic
in
tests
with
various
aquatic
species
(
TOXNET,
HSDB).
The
LC
50
values
to
the
golden
orfe
(
Lueciscus
idus)
range
from
1,000
to
1,500
mg/
L.
The
estimated
toxicity
from
the
ECOSAR
model
(
Meylan
and
Howard,
1998)
indicates
acute
toxicity
to
fish
is
likely
above
the
solubility
of
sorbic
acid
and
as
the
anion,
at
concentrations
approaching
kilo­
grams
per
liter.
Daphnia
magna
and
green
algae
are
among
the
most
sensitive
species
based
on
predictive
modeling
for
chronic
endpoints,
with
the
estimated
adverse
effects
concentrations
ranging
from
an
estimated
80
to
90
mg/
L
for
sorbic
acid
to
low
grams/
liter
for
sorbic
acid
as
a
anion.

VII.
Cumulative
Exposure:
Page
13
of
14
Section
408(
b)(
2)(
D)(
v)
of
the
FFDCA
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,
available
data
to
determine
whether
sorbic
acid
or
its
potassium
salt
have
a
common
mechanism
of
toxicity
with
other
substances.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
sorbic
acid
or
its
potassium
salt
and
any
other
substances,
and
sorbic
acid
or
its
potassium
salt
do
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
sorbic
acid
or
its
potassium
salt
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

References:

Food
and
Drug
Administration
(
FDA).
1975.
Evaluation
of
the
Health
Aspects
of
Sorbic
Acid
And
Its
Salts
As
Food
Ingredients.
Bureau
of
Foods,
U.
S.
FDA,
Department
of
Health,
Education
and
Welfare.
Washington,
D.
C.
Prepared
by
Life
Sciences
Research
Office,
Federation
of
American
Societies
for
Experimental
Biology.
Bethesda
MD.
Performing
Organization
Report
No.
SCOGS­
57.
17
pp.

McCall,
P.
J.,
D.
A.
Laskowski,
R.
L.
Swann,
and
H.
J.
Dishburger.
[
Undated.]
"
Measurements
of
Sorption
Coefficients
of
Organic
Chemicals
on
their
use
in
Environmental
Fate
Analysis."
Agricultural
Products
Department,
Dow
AgroChemicals
USA,
Midland,
MI.
P104
(
89­
109).

Meylan,
W.
and
P.
Howard.
1998.
ECOSAR
Class
Program,
Version
0.99d.
Syracuse
Research
Corporation,
Syracuse,
N.
Y.
For:
U.
S.
Environmental
Protection
Agency,
Office
of
Pollution
Prevention
and
Toxics,
Washington,
D.
C.

Meylan,
W.
and
P.
Howard.
2000.
Estimation
Program
Interface,
Version
3.10.
Syracuse
Research
Corporation,
Syracuse,
N.
Y.
For:
U.
S.
Environmental
Protection
Agency,
Office
of
Pollution
Prevention
and
Toxics,
Washington,
D.
C.

TOXNET.
Department
of
Health
and
Human
Services,
National
Institutes
of
Health,
U.
S.
National
Library
of
Medicine,
Specialized
Information
Services.
Databases:
Hazardous
Substances
Data
Bank
(
HSDB)
and
Chemical
Carcinogenesis
Research
Information
System
(
CCRIS).
Sorbic
Acid
(
CAS
Registry
Number
110­
44­
1).
Available
at
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14
of
14
http://
www.
toxnet.
nlm.
nih.
gov.

TOXNET.
Department
of
Health
and
Human
Services,
National
Institutes
of
Health,
U.
S.
National
Library
of
Medicine,
Specialized
Information
Services.
Databases:
Hazardous
Substances
Data
Bank
(
HSDB).
Potassium
Sorbate
(
CAS
Registry
Number
590­
00­
1).
Available
at
http://
www.
toxnet.
nlm.
nih.
gov.

World
Health
Organization
(
WHO).
1967.
Toxicological
Evaluation
of
Some
Antimicrobials,
Antioxidants,
Emulsifiers,
Stabilizers,
Flour­
Treatment
Agents,
Acids
and
Bases.
034.
Sorbic
Acid.
International
Programme
on
Chemical
Safety,
Food
and
Agriculture
Organization
Nutrition
Meetings
Report
Series
No.
40A,
B,
C.
3
pp.
Available
at
http://
www.
inchem.
org/
documents/
jecfa/
jecmono/
40abcj14.
htm
World
Health
Organization
(
WHO).
1967.
Toxicological
Evaluation
of
Some
Antimicrobials,
Antioxidants,
Emulsifiers,
Stabilizers,
Flour­
Treatment
Agents,
Acids
and
Bases.
036.
Sorbate,
Potassium.
International
Programme
on
Chemical
Safety,
Food
and
Agriculture
Organization
Nutrition
Meetings
Report
Series
No.
40A,
B,
C.
4
pp.
Available
at
http://
www.
inchem.
org/
documents/
jecfa/
jecmono/
40abcj15.
htm
World
Health
Organization
(
WHO).
1973.
Toxicological
Evaluation
of
Some
Food
Additives
Including
Anticaking
Agents,
Antimicrobials,
Antioxidants,
Emulsifiers,
Stabilizers,
and
Thickening
Agents.
274.
Sorbic
Acid
and
its
Calcium,
Potassium
and
Sodium
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International
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on
Chemical
Safety,
Food
and
Agriculture
Organization
(
FAO)
and
WHO.
WHO
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5.
7
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Available
at
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inchem.
org/
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jecmono/
v05je18.
htm