Document ID: EPA-HQ-OPP-2005-0487-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-01-25T05:00Z

Page
1
of
17
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
August
29,
2003
MEMORANDUM
SUBJECT:
Tolerance
Reassessment
Decisions
Completed
by
the
Lower
Toxicity
Pesticide
Chemical
Focus
Group
FROM:
Peter
Caulkins,
Associate
Director
Registration
Division
TO:
Richard
Keigwin,
Acting
Associate
Director
Special
Review
and
Reregistration
Division
Please
find
attached
the
Focus
Group
Decision
Document
for
benzoic
acid
and
its
sodium
salt.
The
four
tolerance
exemptions
for
these
chemicals
in
40
CFR
180.1001
are
reassessed.

If
you
have
any
comments
or
questions,
please
contact
Kathryn
Boyle
at
703­
305­
6304.

Attachments
(
1)
Page
2
of
17
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
benzoic
acid
and
its
sodium,
potassium,
calcium,
ammonium,
and
magnesium
salts.
Based
on
the
rapid
metabolism
and
excretion
of
these
chemicals,
and
the
existing
assessments,
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
benzoic
acid
and
its
sodium,
potassium,
calcium,
ammonium,
and
magnesium
salts
from
their
uses
as
inert
ingredients
in
pesticide
products.
The
benzoic
acid
exemptions
from
the
requirement
of
a
tolerance
as
established
in
40
CFR
180.1001
(
c)
and
(
e)
and
the
sodium
benzoate
exemptions
from
the
requirement
of
a
tolerance
as
established
in
40
CFR
180.1001
(
c)
and
(
e)
are
reassessed.
Based
on
their
rapid
metabolism
and
excretion
and
the
available
information
on
acute
toxicity,
sodium,
potassium,
calcium,
ammonium,
and
magnesium
benzoate
are
reclassified
as
List
4A.
Benzoic
acid
is
classified
as
List
4B
based
on
severe
eye
irritation
(
Toxicity
Category
I).
Page
3
of
17
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
25,
2003
Memorandum
Subject:
Benzoic
Acid
and
Benzoate
salts:
Health
Effects
Division
Science
Assessment
Document
for
Tolerance
Reassessment.

CAS
No.:
65­
85­
0
(
benzoic
acid)
532­
32­
1
(
sodium
benzoate)
582­
25­
2
(
potassium
benzoate)
2090­
05­
3
(
calcium
benzoate)
1863­
63­
4
(
ammonium
benzoate)
563­
70­
8
(
magnesium
benzoate)

Chemical
Class:
benzoates
From:
Elissa
Reaves,
Toxicologist
Reregistration
Branch
2
Health
Effects
Division
(
7509C)

Through:
Pauline
Wagner,
Branch
Chief
Reregistration
Branch
2
Health
Effects
Division
(
7509C)

To:
Lower
Toxicity
Pesticide
Chemical
Focus
Group
Kathryn
Boyle,
Chair
Registration
Division
(
7505C)
Page
4
of
17
Background:

Attached
is
the
Lower
Toxicity
Pesticide
Chemicals
Focus
Group's
science
assessment
for
benzoic
acid,
sodium
benzoate,
and
other
salts
of
benzoic
acid.
This
assessment
summarizes
available
information
on
the
use,
physical/
chemical
properties,
toxicological
effects,
and
exposure
profile
of
these
benzoate
salts.
In
performing
this
assessment,
EPA
has
utilized
reviews
previously
performed
by
EPA
and
FDA
and
relied
on
peer­
reviewed
evaluations
performed
by
the
Cosmetic
Ingredient
Review
(
CIR)
and
FAO/
WHO.

I.
Executive
Summary:

Benzoic
acid,
also
called
benzenecarboxylic
acid,
occurs
naturally
in
certain
foods
such
as
raspberries,
cranberries,
prunes,
cinnamon,
ripe
cloves,
plums,
tea,
anise,
and
oil
of
lovage;
with
most
berries
containing
about
0.05
percent.
Benzoic
acid
and
sodium
benzoate
have
been
used
for
decades
in
pharmaceuticals,
as
a
pH
adjustor
and/
or
preservative
in
cosmetics,
bath
and
beauty
products,
and
as
preservatives/
antimicrobial
agents
in
foods
and
beverages.
Less
is
known
about
the
other
salt
forms
of
benzoic
acid
(
ammonium,
calcium,
magnesium,
and
potassium).
However,
it
was
considered
that
data
gaps
for
one
benzoate
salt
could
be
adequately
addressed
by
the
existing
data
for
the
other
benzoate
compounds.
Benzoic
acid
and
its
salts
are
rapidly
absorbed
by
mammals,
conjugated
with
glycine,
and
rapidly
excreted
in
the
urine
as
hippuric
acid.
There
is
no
reported
accumulation
of
benzoate
in
the
body.
However,
the
ability
to
conjugate
benzoic
acid
depends
upon
adequate
liver
function
and
nutritional
supply
of
glycine.

Toxicological
effects
from
exposure
to
benzoate
solids
documented
in
various
websites
and
from
open
literature
studies
include
irritation
to
the
nose
and
throat,
slight
to
moderate
irritation
to
the
skin,
and
irritation
to
the
eyes.
The
benzoates
were
recognized
to
produce
nonimmunologic
contact
reaction,
but
it
was
not
determined
whether
the
reactions
were
histamine
or
prostaglandin
mediated.
Dermal
sensitization,
photo
toxicity,
and
photosensitization
studies
were
negative.

The
available
ecotoxicity
data
for
benzoic
acid
and
the
benzoate
salts
indicate
that
these
compounds
are
expected
to
be
readily
biodegradable
in
the
environment,
are
of
low
toxicity
to
fish
and
other
aquatic
organisms,
mammals,
and
birds.
EPA
believes
that
benzoic
and
the
benzoate
salts
will
not
cause
unreasonable
adverse
effects
on
the
environment.

Based
on
available
information
on
benzoic
acid
and
benzoate
salts,
their
natural
occurrence
in
berries,
their
expected
use
patterns,
their
safe
history
of
use
as
food
additives,
their
extensive
use
in
cosmetics
and
bath
products,
and
their
low
toxicity,
the
Health
Effects
Division
(
HED)
has
determined
that
a
quantitative
risk
assessment
is
not
warranted
for
these
compounds.

II.
Use
Information:

The
tolerance
exemptions
being
reassessed
in
this
document,
the
40
CFR
location
of
the
established
tolerance
exemption,
and
the
use
pattern
as
an
inert
or
active
ingredient
are
listed
in
Page
5
of
17
Table
1.

Table
1.
Use
Pattern
(
pesticidal­
inert
ingredient)

Chemical
Name
PC
Code
40
CFR
180.1001

Inert
Use
Pattern
(
Pesticidal)
Current
Inert
List*

Benzoic
Acid
809101
(
c)
(
e)
preservative
for
formulations
4B
Sodium
Benzoate
809103
(
c)
(
e)
anticaking
agent,
stabilizer,
preservative
4B
Potassium
Benzoate
709103
non­
food
only
­­

Calcium
Benzoate
900653
non­
food
only
3
Ammonium
Benzoate
809099
non­
food
only
3
Magnesium
Benzoate
900323
non­
food
only
3

Residues
listed
in
section
(
c)
of
40
CFR
180.1001
are
exempted
from
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
when
applied
to
growing
crops
or
to
raw
agricultural
commodities
after
harvest;
residues
listed
in
section
(
e)
of
40
CFR
180.1001
are
exempted
from
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
applied
to
animals.
*
Inert
ingredients
are
categorized
into
four
lists
as
described
in
the
52
FR
13305,
Inert
Ingredients
in
Pesticide
Products
Policy
Statement.
List
3
includes
inert
ingredients
of
unknown
toxicity.
Inert
ingredients
on
this
list
have
not
yet
been
determined
to
be
of
minimal
concern.
List
4
are
inert
ingredients
of
minimal
concern
and
are
subdivided
into
4A
(
minimal
risk
inert
ingredients)
and
4B
(
inert
ingredients
with
sufficient
data
to
substantiate
safe
use
in
pesticide
products).
NA
Not
available
According
to
the
OPPIN
database,
both
benzoic
acid
and
sodium
benzoate
also
have
active
ingredient
PC
Codes,
009101
and
009103,
respectively.
There
are
no
active
or
pending
registrations
for
benzoic
acid
as
an
active
ingredient,
and
only
one
active
registration
for
sodium
benzoate.

Use
Pattern
(
non­
pesticidal):

Benzoic
Acid:
Benzoic
acid
is
generally
recognized
as
safe
(
GRAS)
by
the
U.
S.
FDA
when
used
as
an
antimicrobial
and
flavoring
agent
and
adjuvant
(
21
CFR
184.1021).
The
ingredient
is
used
in
food
levels
not
to
exceed
good
manufacturing
practice
with
a
maximum
usage
level
of
0.1%
in
food.
Benzoic
acid
and
sodium
benzoate
are
also
used
as
a
preservative
in
cosmetic
formulations
with
the
majority
of
both
ingredients
used
at
<
1%
(
Anderson
2001).
Benzoic
acid
and
sodium
benzoate
are
both
also
used
as
a
pH
adjustor
and/
or
preservative
in
bath
and
body
products,
and
in
pharmaceuticals.
The
major
outlet
(
75%)
for
the
production
of
benzoic
acid
is
as
a
chemical
intermediate
in
the
production
of
phenol.
Other
uses
of
benzoic
acid
not
specifically
regulated
includes
the
use
in
paints,
varnishes,
solvents,
cleaning
and
washing
agents,
photo
chemicals
and
antifreeze
agents.

The
Agency
notes
that
benzoic
acid
is
included
on
the
Agency's
list
of
chemicals
included
in
the
High
Production
Volume
(
HPV)
Challenge
Program.
HPV
chemicals
are
those
that
are
Page
6
of
17
manufactured
or
imported
into
the
United
States
in
volumes
greater
than
one
million
pounds
per
year.
There
are
approximately
3,000
HPV
chemicals
that
are
produced
or
imported
into
the
United
States.
The
HPV
Challenge
Program
is
a
voluntary
partnership
between
industry,
environmental
groups,
and
the
EPA
which
invites
chemical
manufacturers
and
importers
to
provide
basic
hazard
data
on
the
HPV
chemicals
they
produce/
import.
The
goal
of
this
program
is
to
facilitate
the
public's
right­
to­
know
about
the
potential
hazards
of
chemicals
found
in
their
environment,
their
homes,
their
workplace,
and
in
consumer
products.

Sodium
Benzoate:
Sodium
benzoate
is
generally
recognized
as
safe
by
the
U.
S.
FDA
when
used
as
an
antimicrobial
and
flavoring
agent
and
adjuvant
(
21
CFR
184.1733).
The
ingredient
is
used
in
food
at
levels
not
to
exceed
good
manufacturing
practice
with
a
maximum
usage
level
of
0.1%
in
food.
The
Cosmetic
Ingredient
Review
(
CIR)
Expert
Panel
concluded
that
benzoic
acid
and
sodium
benzoate
could
be
used
safely
in
cosmetic
formulations
at
concentrations
up
to
5%
(
Anderson
2001).
Sodium
benzoate
is
mainly
produced
for
use
as
a
preservative
in
food
and
beverages
(
60%)
and
is
also
important
for
use
in
cooling
liquids
(
10%).
The
use
of
sodium
benzoate
in
paint
strippers
is
limited
to
uses
in
industrial
settings.
Other
uses
of
sodium
benzoate
may
include
the
use
in
paints,
varnishes,
solvents,
cleaning
and
washing
agents,
photo
chemicals,
and
antifreeze
agents.
The
Agency
notes
that
sodium
benzoate
is
included
on
the
HPV
Challenge
Program.

Ammonium
Benzoate
(
Benzoic
Acid
NH4+):
Ammonium
benzoate
is
regulated
by
the
U.
S.
FDA
as
an
indirect
food
additive
for
the
limited
use
as
a
preservative
component
of
adhesives
(
21
CFR
175.105).
Ammonium
benzoate
is
also
reported
as
an
industrial
preservative
for
paper
wrappers
and
as
an
agent
for
reducing
curing
time
in
vulcanization
of
rubber.
Ammonium
benzoate
is
not
currently
being
sponsored;
however,
it
is
within
the
scope
of
the
HPV
Challenge
Program
and
is
currently
available
for
sponsorship.

III.
Physical/
Chemical
Properties:

Table
2.
Physical/
Chemical
Properties.

Benzoic
Acid
Sodium
Benzoate*
Benzoic
Acid
NH4+

Physical
State
white
solid
white
solid
white
solid
Molecular
Formula
C
6
H
5
COOH
C
6
H
5
COONa+
C
6
H
5
COONH
4+

Molecular
Weight
(
Da)
122.12
144.11
139.16
Melting
Point
°
C
122.4
330.6
198
Water
Solubility
insoluble
soluble
soluble
Density
(
g/
cm3)
1.2659
1.44
1.260
*
Data
for
magnesium
benzoate,
potassium
benzoate
or
calcium
benzoate
are
expected
to
be
similar
to
sodium
Page
7
of
17
benzoate.

IV.
Hazard
Assessment
Table
3.
Summary
of
Acute
Toxicity
Data
on
Benzoic
Acid
and
Sodium
Benzoate.

Benzoic
Acid
Sodium
Benzoate
Test
Species
Results
Category
Species
Results
Category
Oral
LD50
rat
2565
mg/
kg
III
rat
3140
mg/
kg
III
Dermal
LD50
rabbit
>
2000
mg/
kg
III
no
data
Inhalation
LC50
rat
>
12.2
mg/
l/
4h.
IV
no
data
Eye
Irritation
rabbit
severe
irritation
I
rabbit
slightly
irritating
III
Dermal
Irritation
rabbit
non
to
slightly
irritating
III
rabbit
non­
irritating
IV
Dermal
Sensitization
guinea
pig
not
sensitizing
Not
applicable
human
nonimmunologic
contact
urticaria
Not
applicable
A.
Toxicological
Profile:
The
general
effects
of
exposure
to
benzoic
acid
and
sodium
benzoate
or
its
salts
include
nose
and
throat
irritation
if
inhaled,
as
well
as
slight
skin
and
severe
eye
irritation.
Benzoic
acid
and
the
benzoate
salts
are
rapidly
metabolized
and
excreted,
do
not
bioaccumulate,
and
have
low
toxicity
after
acute
and
repeated
exposures.
Early
human
consumption
studies
indicated
no
externally
visible
effects
from
ingesting
0.5
to
1.0
g/
day
of
benzoic
acid
for
44
consecutive
days
or
for
82/
86
or
88/
92
days
(
Gerlach
1909;
as
cited
in
USEPA
IRIS).
Assuming
a
human
body
weight
of
70
kg,
this
corresponds
to
a
dose
of
14
mg/
kg/
day
of
benzoic
acid.
In
another
early
study
(
1909),
men
who
drank
from
1
to
2.5
liters
of
apple
juice
containing
0.1
percent
sodium
benzoate
complained
of
burning
taste,
headache,
nausea
and
vomiting,
itching
of
the
skin,
sweating,
constipation
and
albuminuria.
However,
massive
doses
of
sodium
benzoate
(
25­
60
g
per
day)
were
given
to
rheumatic
patients
Page
8
of
17
without
producing
any
harmful
effects
(
FDA
1973).
Adverse
effects
in
humans
given
an
oral
bolus
dose
of
less
than
or
equal
to
1.75
g/
day
of
benzoic
acid
over
a
20­
day
period
include
observed
irritation,
discomfort,
weakness,
and
malaise
(
Wiley
and
Bigelow
1908;
as
cited
in
USEPA
IRIS).

The
oral
LD50
for
benzoic
acid
is
1,520
mg
for
the
rabbit
and
2,000
mg
for
the
cat
and
dog.
The
lethal
dose
for
benzoic
acid
in
sheep
is
estimated
to
be
1,000
mg/
kg
(
FDA
1973).

A
chronic
oral
dose
of
40
mg/
kg/
day
of
benzoic
acid
for
17
months
was
associated
with
decreased
resistance
to
stress
in
mice
and
possibly
with
reduced
food
and
water
intake
in
rats
after
18
months.
However,
another
study
reported
by
the
same
laboratory
indicated
80
mg/
kg/
day
in
rats
for
18
months
was
not
associated
with
adverse
effects
on
body
weight,
survival,
or
gross
or
microscopic
pathology
(
Shtenberg
and
Ignat'er
1970;
Ignat'er
1965;
as
cited
in
USEPA
IRIS).
Other
long­
term
dietary
studies
showed
decreased
food
intake
and
body
weight
in
rats
fed
1.5%
benzoic
acid
(
750
mg/
kg/
day).
A
reduced
dose
of
1.0%
benzoic
acid
in
the
diet
(
50
mg/
kg/
day)
did
not
produce
signs
of
toxicity
or
adverse
reproductive
effects
(
Marquardt
1960;
as
cited
in
USEPA
IRIS).

No
positive
results
have
been
reported
for
benzoic
acid
or
sodium
benzoate
when
tested
for
mutagenicity
or
genotoxicity
in
prokaryotes,
eukaryotes,
and
several
mammalian
test
systems
(
McCann
et
al.,
1975;
Litton
Bionetics,
Inc.,
1975
and
1975;
Oikawa
et
al.,
1980;
as
cited
in
USEPA
IRIS).

B.
Cations:
Ammonium,
Calcium,
Magnesium,
Potassium,
and
Sodium:

Calcium:
The
human
body
burden
of
calcium
is
approximately
1
kg
for
a
70
kg
adult;
thus,
1/
70th
of
our
weight
is
calcium.
The
calcium
cation
is
necessary
for
bone
and
teeth
formation.
It
is
also
important
to
the
proper
functioning
of
nerves,
enzymes,
and
muscles,
and
plays
a
role
in
blood
clotting
and
the
maintenance
of
cell
membranes.
The
recommended
daily
allowances
(
RDAs)
for
calcium
are
1000
mg/
day
for
adults
aged
19
to
50
years,
and
1200
mg/
day
for
individuals
older
than
50
years.

Magnesium:
The
human
body
burden
of
magnesium
is
approximately
20
g
for
a
70
kg
adult.
The
magnesium
cation
is
also
used
in
building
bones.
It
plays
a
role
in
releasing
energy
from
muscles
and
regulating
body
temperature.
The
RDA
is
310
to
320
mg/
day
for
adult
females,
and
400
to
420
mg/
day
for
adult
males,
with
the
RDA
increasing
with
increasing
age.

Potassium:
The
human
body
burden
of
potassium
is
approximately
140
g
for
a
70
kg
adult.
The
potassium
cation
is
important
in
regulating
blood
pressure,
regulating
cellular
water
content,
maintaining
proper
pH
balance,
and
transmission
of
nerve
impulses.
It
helps
to
regulate
the
electrical
activity
of
the
heart
and
muscles.
The
potassium
RDA
is
900
mg/
day.

Sodium:
The
human
body
burden
of
sodium
is
approximately
20
g
for
a
70
kg
adult.
The
sodium
cation
is
necessary
for
the
nerves
and
muscles
to
function
properly.
It
is
the
principal
Page
9
of
17
cation
of
extracellular
fluid,
and
helps
to
maintain
the
body's
water
balance.
These
electrolytes,
the
electrically
charged
ions
in
the
body
fluids,
consist
to
a
great
extent
of
sodium
and
potassium.
There
is
no
Recommended
Daily
Allowance
(
RDA)
for
sodium.

C.
Ammonium
Salt:

Ammonium
salts
dissociate
to
the
negatively
charged
anion
and
the
positively
charged
ammonium
cation
(
NH
4
+).
Humans
cannot
convert
atmospheric
nitrogen
to
any
form
that
can
be
used
as
part
of
any
of
the
various
metabolic
cycles.
Therefore,
reduced
nitrogen
(
NH
4
+)
has
to
enter
the
body
from
an
outside
source.
These
sources
are
the
nitrogen­
containing
amino
acids
in
protein
which
are
consumed
daily
as
part
of
the
diet.
Although
the
human
body
can
produce
some
amino
acids,
ten
amino
acids
are
considered
"
essential"
amino
acids,
i.
e.,
they
must
be
consumed
in
the
diet.

Generally
the
body
works
to
maintain
a
balance
of
nitrogen
intake
and
nitrogen
excretion.
The
estimated
daily
ammonia
intake
through
food
and
drinking
water
is
18
mg.
In
contrast,
4000
mg
of
ammonia
per
day
are
produced
endogenously
in
the
human
intestine.

Ammonia
and
the
ammonium
ion
are
integral
components
of
normal
human
metabolic
processes.
Ammonia
is
released
following
deamination
that
occurs
when
protein
is
used
by
the
body
for
energy
production.
The
liver
converts
ammonia
via
the
urea
cycle
into
urea.
According
to
FDA
in
the
"
Evaluation
of
the
Health
Aspects
of
Certain
Ammonium
Salts
as
Food
Ingredients"
(
1974),
"
the
normal
liver
so
readily
detoxifies
ammonium
ion
from
alimentary
sources
that
blood
concentrations
of
ammonium
salts
do
not
rise
to
the
levels
necessary
to
evoke
toxic
response."
Approximately
80%
of
the
body's
excess
nitrogen
is
eliminated
through
the
kidneys
as
urea,
approximately
25
to
30
grams
per
day.

D.
Special
Considerations
for
Infants
and
Children
Given
the
wide
spread
occurrence
of
benzoates
in
the
food
supply,
the
amount
of
benzoates
that
can
be
applied
to
food
as
a
result
of
its
use
in
a
pesticide
product
should
not
significantly
increase
the
existing
amounts
in
the
food
supply.
Oral
doses
of
sodium
benzoate
appeared
to
have
no
maternal
toxicity,
fetal
toxicity,
or
teratogenicity
in
mice,
rats,
hamsters,
or
rabbits
with
the
highest
doses
tested
being
175.0
mg/
kg/
day
in
mice
and
rats,
300.0
mg/
kg/
day
in
hamsters,
and
250.0
mg/
kg/
day
in
rabbits
(
FDRL
1972;
as
cited
in
USEPA
IRIS).

However,
there
is
some
concern
that
low
birth
weight
or
premature
infants
with
immature
livers
can
experience
adverse
effects
when
administered
benzoic
acid
or
benzoate
salts.
Infants
with
immature
livers
may
not
be
capable
of
metabolizing
benzoate.
It
was
suggested
that
a
combination
of
sodium
benzoate
and
sodium
phenylacetate
not
be
administered
to
low
birth
weight
infants
unless
the
benefits
outweigh
the
risks
(
AMA
1991;
USP
DI
1992,
as
cited
in
TOXNET).
Page
10
of
17
EPA
believes
there
would
be
a
very
low
exposure
of
premature
or
very
young
infants
to
benzoates.
First,
premature
or
very
young
infants
ingest
only
formula
or
breast
milk.
(
It
is
generally
recommended
that
infants
not
consume
solid
food
until
4
to
6
months
of
age.)
Regulation
of
infant
formulas
is
under
the
purview
of
the
FDA.
(
www.
fda.
gov/
fdac/
features/
596_
baby.
html).

Benzoic
acid
and
sodium
benzoate
are
generally
recognized
as
safe
(
GRAS)
under
21
CFR
184.1021
and
184.1733,
respectively.
Therefore,
infants
consuming
only
infant
formula
or
breast
milk
would
be
exposed
to
very
low
amounts
of
benzoates.
Second,
even
if
a
young
infant
were
to
be
fed
some
solid
food,
given
the
characteristics
of
benzoic
acid
and
benzoate
salts,
residues
are
not
likely
to
be
present
above
naturally
occurring
concentrations.
As
discussed
below
(
section
7)
the
benzoates
are
readily
biodegradable.
It
is
not
likely
to
be
taken
up
by
plants.

Once
past
this
several
month
time­
period,
there
is
no
longer
a
concern
for
potential
sensitivity
to
infants
and
children.
Older
infants,
like
adults,
process
benzoates
through
well
understood
metabolic
pathways.
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
Benzoic
acid
and
sodium
benzoate
have
been
used
for
decades
in
pharmaceuticals,
cosmetics
and/
or
in
food
as
preservatives
and
flavoring/
fragrance
agents.
According
to
information
in
Product
Registers
the
substances
are
also
used
in
different
kinds
of
products,
such
as
in
paints,
varnishes,
solvents,
cleaning
and
washing
agents,
photo
chemicals,
and
antifreeze
agents.
Benzoic
acid
and
sodium
benzoate
both
have
the
status
"
generally
recognized
as
safe"
(
GRAS)
by
the
U.
S.
FDA.
An
estimated
daily
food
input
of
benzoate
by
the
U.
S.
EPA
was
278
mg
as
sodium
benzoate
and
34
mg
as
benzoic
acid.
(
USEPA
1987;
as
cited
in
USEPA
IRIS).
In
1983,
the
Joint
Expert
Committee
on
Food
Additives
(
JEFCA)
of
the
World
Health
Organization
(
WHO)
established
a
group
acceptable
daily
intake
(
ADI)
for
benzoic
acid
and
its
salt
of
5
mg/
kg
body
weight.
This
group
ADI
is
based
on
the
structural
similarity
and
common
metabolic
fate
of
these
chemicals
(
WHO
1997).

The
National
Research
Council
subcommittee
also
provided
a
possible
daily
human
intake
of
benzoic
acid
and
sodium
benzoate
in
the
total
diet
based
on
a
comprehensive
survey.
The
following
table
summarizes
the
possible
daily
intake
for
individuals
in
various
age
groups
(
FDA
1973).

Table
4.
Possible
daily
intake
Total
Intake
mg
mg/
kilogram
of
body
weight*

Benzoic
Acid
Sodium
Benzoate
Benzoic
Acid
Sodium
Benzoate
Age
group
Avg.
Max.
Avg.
Max
Avg.
Max.
Avg.
Max.

0­
5
mos.
0.6
1
10
21
.1
.2
2
4
6­
11
mos.
6
21
111
313
.8
2.6
14
39
Page
11
of
17
12­
23
mos.
16
46
188
404
1.4
4.2
17
37
2­
65+
yrs.
34
87
328
669
0.6
1.4
5.5
11
*
Calculations
based
on
an
average
weight
of
60
kg
for
an
adult
and
the
following
estimated
weights
of
infants
by
age
groups:
0­
5
mos.,
5
kg;
6­
11
mos.,
8
kg;
and
12­
23
mos.,
11
kg.

It
should
also
be
noted
that
the
NRC
subcommittee
stated
the
calculations
of
benzoate
intakes
are
likely
over
stated,
possibly
by
considerable
margins.
The
Select
Committee
regarded
the
figures
given
in
the
table
as
levels
that
would
unlikely
be
consumed
by
any
of
the
age
groups.
Figures
in
the
table
were
considered
to
be
generous
overestimates
of
the
benzoic
acid
and
sodium
benzoate
content
of
the
human
diet
(
FDA
1973).

The
worldwide
production
capacity
for
benzoic
acid
is
estimated
at
700
kt.
The
major
outlet
(
75%
or
525
kt)
for
benzoic
acid
is
for
the
production
of
phenol,
which
in
turn
is
mainly
used
to
produce
caprolactam.
The
next
biggest
outlet
is
as
a
feedstock
for
sodium
benzoate
(
10%
or
70
kt)
and
chemical
synthesis
of
plasticizers
(
5%
or
35
kt).
So,
benzoic
acid
is
mainly
used
in
controlled
industrial
settings.

The
worldwide
production
of
sodium
benzoate
is
estimated
at
100
kt.
The
major
use
for
sodium
benzoate
is
as
a
preservative
in
food
and
beverages
(
60%
or
60
kt).
The
second
most
important
market
for
sodium
benzoate
is
for
cooling
liquids
(
10%
or
10
kt).
Like
sodium
benzoate,
potassium
benzoate
is
used
mainly
as
a
preservative
in
nonalcoholic
beverages
with
an
estimated
worldwide
production
capacity
of
only
7
kt.
Ammonium
benzoate
is
approved
only
as
an
indirect
food
additive
for
use
only
as
component
of
adhesives
(
21
CFR
175.105).
No
production
estimates
could
be
determined
for
ammonium
benzoate
or
any
of
the
other
benzoate
salts.

The
use
of
benzoic
acid
and
sodium
benzoate
in
pesticide
products
as
inert
ingredients
is
expected
to
result
in
much
lower
exposure
than
the
FDA­
regulated
use
of
these
compounds,
as
well
as
lower
exposure
than
in
the
average
daily
intake
of
benzoates.
Therefore,
a
quantitative
screening­
level
exposure
assessment
has
not
been
conducted.

VI.
Risk
Characterization
Benzoic
acid
is
a
naturally
occurring
compound
found
in
berries
and
other
foods.
As
previously
discussed
in
this
document,
there
are
many
FDA
approved
uses
for
benzoic
acid
and
the
benzoate
salts.
Residues
from
the
pesticide
uses
of
the
benzoates
are
not
likely
to
greatly
contribute
to
the
levels
already
approximated
as
the
average
daily
intake.

As
noted
previously,
three
of
the
benzoates
assessed
in
this
document,
benzoic
acid,
sodium
benzoate,
and
ammonium
benzoate,
are
included
on
the
Agency's
list
of
chemicals
included
in
the
High
Production
Volume
(
HPV)
Challenge
Program.
HPV
chemicals
are
those
that
are
manufactured
or
imported
into
the
United
States
in
volumes
greater
than
one
million
pounds
per
year.
There
are
approximately
3,000
HPV
chemicals
that
are
produced
or
imported
Page
12
of
17
into
the
United
States.
The
HPV
Challenge
Program
is
a
voluntary
partnership
between
industry,
environmental
groups,
and
the
EPA
which
invites
chemical
manufacturers
and
importers
to
provide
basic
hazard
data
on
the
HPV
chemicals
they
produce/
import.
The
goal
of
this
program
is
to
facilitate
the
public's
right­
to­
know
about
the
potential
hazards
of
chemicals
found
in
their
environment,
their
homes,
their
workplace,
and
in
consumer
products.
Based
on
the
available
toxicity
data
for
the
benzoates,
the
Agency
feels
confident
in
proceeding
with
this
tolerance
reassessment
decision.
Any
submission
of
data
by
sponsors
of
benzoic
acid,
sodium
benzoate,
and
ammonium
benzoate
as
part
of
the
HPV
Challenge
Program
may,
in
the
future,
be
used
by
OPP
to
revise
or
update
their
tolerance
reassessment
decision
for
these
benzoates
as
deemed
necessary
and
appropriate.

Taking
into
consideration
all
available
information
on
benzoic
acid,
sodium
benzoate,
and
the
other
salts
of
benzoate,
including
the
FDA's
designation
of
GRAS
for
benzoic
acid
and
sodium
benzoate,
as
preservatives/
antimicrobial
agents
in
foods
and
beverages,
the
historical
use
of
benzoic
acid
and
sodium
benzoate
in
pharmaceuticals,
cosmetics,
as
well
as
the
natural
presence
of
benzoic
acid
in
berries,
the
use
of
ammonium
benzoate
as
a
preservative
in
adhesive
components
in
foods,
the
use
of
benzoic
acid
and
the
benzoate
salts
as
inert
ingredients
in
pesticide
formulations
are
unlikely
to
pose
a
significant
hazard
to
the
general
public
or
any
population
subgroup.
Therefore,
HED
is
conducting
a
qualitative
approach
to
assessing
human
health
risks
from
exposure
to
benzoates.

VII.
Environmental
Fate/
Ecotoxicity/
Drinking
Water
Considerations:

The
environmental
fate
and
occurrence
of
benzoic
acid
has
been
well
studied.
The
Hazardous
Substances
Database
(
HSDB)
(
www.
toxnet.
nlm.
nih.
gov)
contains
extensive
summaries
of
the
environmental
fate
of
benzoic
acid.
In
addition,
HSDB
information
has
been
supplemented
with
predictive
modeling
based
on
structure
activity
relationships.
For
this
analysis,
sodium,
potassium
calcium,
and
magnesium
salts
were
considered
equivalent
with
respect
to
their
environmental
fate
and
ecotoxicity.
Slight
differences
in
physical­
chemical
properties
were
observed,
but
are
not
expected
to
impact
their
behavior
or
toxicity
in
the
environment.
Benzoic
acid
and
the
ammonium
salt
of
benzoic
acid
were
addressed
separately.

Table
1
provides
key
fate
and
chemical
properties
for
benzoic
acid
and
representative
molecules
of
the
salts.
With
a
pKa
of
4.204,
benzoic
acid
will
dissociate
to
form
an
anion
at
environmental
pH
up
to
the
limits
of
its
solubility.
The
benzoate
salts
are
highly
water
soluble
and
readily
dissociate
into
the
anion
(
benzoic
acid)
and
cation
(
sodium,
potassium,
calcium,
magnesium
and
ammonium
ion).
Thus,
the
environmental
fate
and
effects
of
the
benzoic
acid
salts
are
closely
related
to
that
of
benzoic
acid,
and
the
free
cation.

Table
1.
Properties
and
Environmental
Fate
of
Benzoic
Acid
and
Selected
Salts
Property
Benzoic
Acid
Sodium
Benzoate
Benzoic
Acid,
Ammonium
Salt
Page
13
of
17
Water
Solubility
(
mg/
L)
@
25C
3400
(
M)
5.56E05
(
M)
>
1.0E06
(
E)

Vapor
Pressure
mm
Hg
@
25C
7E­
04
(
M)
3.67E­
09
(
E)
2.65E­
07
(
E)

Henry's
Law
Coefficient
(
atm­
m3/
mole)
3.8E­
08
(
M)
1.09E­
07
(
E)
5.2E­
16
(
E)

Biodegradation
Primary:
hours­
days
Ultimate:
days­
weeks
Primary:
hours­
days
Ultimate:
days­
weeks
Primary:
hours­
days
Ultimate:
days­
weeks
Log
Kow
1.87
(
M)
­
2.27
(
E)
­
1.33
(
E)

Koc
(
ml/
g)
14
(
E)
14
(
E)
99
Hydrolysis
Half­
life
@
pH
7
(
days)
No
hydrolizable
functional
groups
No
hydrolizable
functional
groups
52
days
M:
Measured;
E:
Estimated
Based
on
low
K
oc
s
and
log
K
ow
s,
benzoic
acid
and
its
salt
are
classified
as
highly
mobile
in
soil
(
McCall).
Volatilization
from
water
would
be
minimal,
based
on
both
benzoic
acid
and
the
salts'
low
Henry's
Law
constant.
All
compounds
have
a
low
potential
to
volatilize
from
soil
surfaces,
based
on
vapor
pressures
of
less
than
1
x
10­
4
mm
Hg.

The
biodegradability
of
benzoic
acid
has
been
extensively
studied
and
are
expected
to
be
readily
biodegradable
in
the
environment.
Using
both
unacclimated
and
acclimated
sludge
inoculums,
benzoic
acid
degraded
with
half­
lives
of
less
than
approximately
5
days.
In
most
all
cases,
near
complete
mineralization
occurred
in
under
10
days.
In
soil
inoculums,
benzoic
acid
exhibited
a
half­
life
for
mineralization
of
4.5
hours.
In
a
second
study,
complete
mineralization
occurred
in
one
day.
Benzoic
acid
degraded
in
a
polluted
river
water
in
0.85
days
and
in
reservoir
water
in
3.6
days.
Degradation
appears
to
be
concentration
dependent,
with
low
concentrations,
less
than
1
ppb,
mineralizing
in
eutrophic
and
oligotrophic
lake
water
in
under
7
days.
Overall
half­
lives
in
unacclimated
and
acclimated
systems
ranges
from
hours
to
days
for
primary
degradation
and
hours
to
weeks
for
ultimate
(
mineralization)
degradation.

In
an
acidic
soil,
benzoic
acid
mineralized
up
to
80
percent
in
less
than
12
weeks.
The
same
experiment
in
a
neutral
soil
resulted
in
approximately
70
percent
mineralized
in
12
weeks.
Anaerobically,
more
than
75
percent
of
benzoic
acid
mineralizes
when
incubated
for
8
weeks
using
sludge
from
a
secondary
digester.
In
several
other
experiments
using
sewage
sludge
inoculums,
benzoic
acid
mineralized
>
90
percent
in
as
little
as
7
to
18
days.
In
a
study
using
anoxic
sediment
from
a
hypereutrophic
lake
in
Kalamazoo,
MI,
benzoic
acid
degraded
completely
(
methane
and
CO
2
)
in
one
week.

Due
to
the
lack
of
hydrolyzable
functional
groups,
abiotic
degradation
of
benzoic
acid
and
the
salts
of
benzoate
would
not
be
expected
to
be
an
important
fate
process.
However,
the
ammonium
salt
would
hydrolyze
in
neutral
to
alkaline
environments
from
5
days
at
pH
8
to
52
Page
14
of
17
days
at
pH
7.
Benzoic
acid
is
expected
to
photolyze
based
on
UV
adsorption
at
310nm.
Available
data
indicate
that
10.2
percent
photolyzes
in
approximately
17
hours.

If
any
of
these
compounds
were
to
enter
the
atmosphere,
it
is
expected
to
exist
solely
as
a
vapor.
Vapor­
phase
benzoic
acid
would
be
readily
degraded
in
the
atmosphere
by
reaction
with
photochemically­
produced
hydroxyl
radicles
with
an
estimated
half­
life
of
8
days.

Estimated
toxicity
(
Meylan,
1998)
indicates
benzoic
acid
is
the
most
toxic
of
the
substances
reviewed
in
this
assessment.
Table
2
lists
the
estimated
toxicity
for
several
species.
Green
algae
and
fish
are
among
the
most
sensitive
species
based
on
predictive
modeling
for
acute
and
chronic
endpoints
for
all
compounds.
Based
on
the
environmental
fate
profile
of
benzoic
acid
and
its
salts,
exposures
from
labels
uses
are
unlikely
to
reach
concentrations
necessary
to
elicit
effects
in
aquatic
organisms.
Using
laboratory
rat
data
as
a
surrogate
for
terrestrial
wild
mammals
and
birds,
benzoic
acid
and
its
salts
do
not
appear
to
be
very
toxic
and
adverse
effects
from
labeled
uses
is
not
expected.

Table
2.
Ecotoxicity
of
Benzoic
Acid
and
Selected
Salts
Property
Benzoic
Acid
Sodium
Benzoate
Benzoic
Acid,
Ammonium
Salt
Fish
(
96­
h
LC50;
mg/
L)
1200
>
1.0E06
1.4E05
Daphnid
(
48­
h
LC50;
mg/
L)
1274
8.8E05
1.2E05
Green
Algae
(
96­
h
EC50;
mg/
L)
790
4.3E05
61172
Fish
(
30­
day
Chronic;
mg/
L)
151
71380
10486
Fish
(
SW)
(
96­
h
LC50;
mg/
L)
258
32047
6374
Mysid
Shrimp
(
96­
h
LC50;
mg/
L)
380
>
1.0E06
4.3E05
Green
Algae
(
96­
h
Chronic;
mg/
L)
73
3646
893
Earthworm
(
14­
day
LC50;
mg/
Kg
dry
wt.)
8238
18317
9081
Detections
of
benzoic
acid
in
surface
water
have
been
extensively
reported,
but
not
quantified.
In
ground
water,
concentrations
of
<
0.1
ppb
have
been
reported
for
areas
without
known
sources
of
potential
contamination
such
as
landfills,
wood
preserving
facilities,
and
petroleum
operations.
Benzoic
acid
has
been
detected
in
the
particulate
fraction
of
rain
and
snow.
In
drinking
water,
concentrations
of
up
to
15
ppm
in
the
tap
water
of
Otumwa,
IA
was
reported,
but
was
not
detected
in
water
from
utilities
in
Seattle,
Philadelphia,
or
Cincinnati.
Benzoic
acid
has
been
detected,
but
not
quantified,
in
other
drinking
water
monitoring
studies,
domestically
and
internationally.
Overall,
and
with
few
exceptions,
concentrations
of
benzoic
acid
in
ambient
and
drinking
water
is
expected
to
be
in
the
low
ppb
range.
Page
15
of
17
VIII.
Cumulative
Exposure:

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
benzoic
acid
or
the
benzoate
salts
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
benzoic
acid
or
the
benzoate
salts
and
any
other
substances
and
benzoic
acid
or
the
benzoate
salts
do
no
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
benzoic
acid
or
the
benzoate
salts
have
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:

(
Note
to
the
Reader:
MRID
(
Master
Record
Identification)
Numbers
were
added
to
the
references
on
October
17,
2003
and
November
21,
2003.
These
numbers
were
not
available
at
the
time
of
document
signature.
No
other
changes
were
made
to
the
document.)

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