Document ID: EPA-HQ-OPP-2002-0280-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-10-02T04:00Z

Page
1
of
16
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
March
28,
2002
MEMORANDUM
FROM:
Kathryn
Boyle,
CoChair
IIFG
and
Kerry
Leifer,
CoChair
IIFG
TO:
Robert
Forrest,
Chief
Minor
Use,
Inerts,
and
Emergency
Response
Branch
SUBJECT:
February
26
Meeting
of
the
IIFG
Decision
Memo
Please
find
attached
the
Inert
Ingredient
Focus
Group
recommendations
for
the
inert
ingredients
associated
with
acetic
acid
and
the
citric
acid
cycle
grouping.
Page
2
of
16
INERT
INGREDIENT
FOCUS
GROUP
DECISION
DOCUMENT
for
Acetic
Acid
and
Salts
Citric
Acid
Cycle
Chemicals
and
Salts
Petition
No.:
no
Tolerance
Reassessments?:
yes
Common
Chemical
Names:
acetic
acid,
sodium
acetate,
citric
acid,
sodium
citrate,
potassium
citrate,
calcium
citrate,
malic
acid,
and
fumaric
acid
Chemical
Category/
Group:
organic
acids
and
their
salts
CAS.
Reg.
No.:
in
tables
HPV
Chemical?
yes
Data
Posted?
yes
Use
Pattern
(pesticidal):
Citric
acid
and
malic
acid
are
FIFRA
25(
b)
active
ingredients.
As
an
active
ingredient,
citric
acid
is
used
as
a
disinfectant,
sanitizer,
fungicide
and
scale
remover
for
use
in
toilets
and
food
processing
equipment.
Both
citric
acid
and
fumaric
acid
are
in
40
CFR
180.2.
Acetic
acid
and
citric
acid
are
used
in
food­
contact
surface
sanitizing
solutions.
As
an
active
ingredient
acetic
acid
is
used
on
rights
of
ways,
golf
courses,
open
spaces,
driveways
and
industrial
sites
at
concentrations
similar
to
that
in
vinegar
to
dessicate
(dry
out)
plants.

Use
Pattern
(non­
pesticidal):
These
are
naturally
occurring
chemicals,
food
acids
that
are
found
in
a
wide
variety
of
unprocessed
foods,
especially
fruits.
FDA
clearances
exist
for
these
chemicals
allowing
their
use
in
candy,
jelly,
ice
cream,
cakes,
cookies,
pies,
soft
drinks,
fruit
drinks,
cheese,
and
animal
drugs
and
feeds.
Malic
acid
is
a
flavoring
agent.
Fumaric
acid
is
an
antioxidant
and
can
be
a
component
of
adhesives.
Citric
acid
can
be
used
in
various
cleaners
and
strippers.
Page
3
of
16
1.
Physical/
Chemical
Properties:

Table
1.
Chemical
Properties
of
Acetic
Acid
and
Salts
Chemical
Property
Acetic
Acid
Acetic
Acid,
Calcium
salt
Acetic
Acid,
Magnesium
salt
Acetic
Acid,
Potassium
salt
Acetic
Acid,
Sodium
salt
Vapor
Pressure
(mmHg)
11.4
@
20
o
C
14.7
@25
o
C
NA
7.
08x10
­7
@25
o
C
7.08x10
­7
@25
o
C
Log
Kow
­0.17
­0.97
NA
­3.72
­3.72
Kd's
(Koc)
0.
65
(228)
Clastic
mud
0.085
(6.5)
muddy
sand
0.046
(27)
carbonate
sand
NA
NA
NA
NA
Water
Solubility
(g/
L)
50
@20
o
C
430
@25
o
C
very
soluble
2530
@25
o
C
365
@20
o
C
pKa
4.
76
@25
o
C
NA
NA
NA
NA
Photodegradation
50%
after
21
days
NA
NA
NA
6.6%
after
17h
Biodegradation
99%
after
7
days
using
AS
*
Readily
biodegrades
NA
NA
100%
after
5
days
using
AS
Fish
Acute
Toxicity
96h
LC50)
75mg/
L
(Lowest
value
­
Bluegill
sunfish)
NA
NA
>6100mg/
L
(rainbow
trout)
100mg/
L
(zebra
fish)

Daphnia
Acute
Toxicity
65mg/
L
48h
EC50)
NA
NA
7170mg/
L
24h
LC50)
>1000mg/
L
(48h­
EC50)

Algae
Toxicity
4000mg/
L
(8­
day
growth
inhibition)
NA
NA
NA
2460mg/
L
after
60­
h
growth
inhibition)

Mammal
Acute
Oral
(LD50)
4960
mg/
kg­
bw
(mouse)
4280mg/
kg
bw
(rat)
8610mg/
kg
bw
(rat)
3250mg/
kg­
bw
(rat)
3530mg/
kg­
bw
(rat)

*
AS:
Activated
Sludge.
Page
4
of
16
Table
2.
Chemical
Properties
of
Citric
Acid
and
Salts
Chemical
Property
Citric
Acid
Citric
Acid,
Sodium
salt
Citric
Acid,
Tripotassium
salt
Citric
Acid,
Trisodium
salt
Vapor
Pressure
(mmHg@
25
o
C)
3.7x10
­9
@25
o
C
NA
NA
2.09x10
­12
@25
o
C
Log
Kow
­1.72
NA
NA
­0.28
Water
Solubility
(g/
L
@25
o
C)
1330
@20
o
C
NA
NA
~425
@25
o
C
pKa
pK1:
3.
13;
pK2:
4.76;
pK3:
6.4
NA
NA
NA
Photodegradation
NA
NA
NA
NA
Biodegradation
98%
after
48­
h
using
domestic
sewage
NA
NA
90%
after
48­
h
using
AS
Fish
Acute
Toxicity
(96h­
LC50)
1516mg/
L
(Bluegill
sunfish)
NA
NA
>18000­
32000mg/
L
(guppy)

Daphnia
Acute
Toxicity
120mg/
L
72h
EC50)
NA
NA
5600­
10000mg/
L
(48h­
EC50)

Algae
Toxicity
640mg/
L
8­
day
growth
inhibition)
NA
NA
>18000­
32000mg/
L
(96h­
EC50)

Mammal
Acute
Oral
5790mg/
kg­
bw
(mouse)
7100mg/
kg­
bw
(mouse)
NA
NA
Table
3.
Chemical
Properties
of
Fumaric
and
Malic
Acid
Chemical
Property
Fumaric
Acid
Malic
Acid
Vapor
Pressure
(mmHg@
25
o
C)
1.54x10
­4
4.6x10
­6
Log
Kow
0.33
@23
o
C
­1.26
Water
Solubility
(g/
L
@25
o
C)
7
592
pKa
pK1:
3.
02;
pK2:
4.46
@18
o
C
pK1:
3.
4;
pK2:
5.
05
Photodegradation
50%
degradation
after
7.3h
50%
degradation
after
2
days
Page
5
of
16
Biodegradation
98%
after
21
days
using
domestic
sewage
readily
biodegrades
Fish
Acute
Toxicity
245mg/
L
(48h­
LC50
­zebra
fish))
NA
Daphnia
Acute
Toxicity
212
mg/
L
(48h­
EC50)
240mg/
L
(48h­
EC50)

Algae
Toxicity
41mg/
L
(72h­
EC50
­
green
algae)
NA
Rat
Acute
Oral
9300mg/
kg­
bw
(female
rat)
1600­
3200mg/
kg­
bw
(mouse,
rat)

2.
Introduction:

Acetic
acid
is
produced
in
biological
tissues
by
fermentation
of
carbohydrates
and
also
by
organic
synthesis.
Vinegar
which
is
a
5
to
8
%
solution
of
acetic
acid,
is
also
a
commonly
consumed
food.

Citric
acid
is
widely
distributed
in
plants
and
animals
and
occurs
naturally
in
foods
such
as
citrus
fruits
and
tomatoes
in
substantial
quantities.
It
is
also
one
of
the
most
widely
used
food
additives.
As
a
dietary
supplement,
calcium
citrate
is
a
source
of
calcium.

Malic
acid
occurs
naturally
as
the
major
acid
in
apples,
apricots,
cherries,
carrots
and
other
foods.
It
is
also
used
as
a
flavor
booster
in
candy,
jelly
fruit
drinks
and
ice
cream.

Fumaric
acid
occurs
in
apples,
beans,
and
carrots.
It
is
commonly
used
to
control
pH
and
produce
light
textures
in
such
foods
as
cake
and
cookies.

The
following
information
was
used
in
performing
this
assessment:
The
available
information
consisted
of
information
retrieved
from
various
websites,
such
as,
°EPA(
www.
epa.
gov),
°NIOSH,(
www.
cdc.
gov/
niosh/
ipcsneng/
neng0000.html)
and
(www.
cdc.
gov/
niosh/
npg/
npg.
html)
°
TOXNET
(
www.
toxnet.
nlm.
nih.
gov.),
°NTP(
ntp­
server.
niehs.
nih.
gov.),

Additional
information
included
the
information
submitted
to
EPA's
High
Production
Volume
Challenge
Program
"Assessment
Plan
and
Robust
Summaries
for
the
Acetic
Acid
and
Salts
Category."
(Submitted
June
28,
2001)
Citric
acid
was
also
previously
evaluated
by
the
Agency
in
1992
in
the
Citric
Acid
RED.
Information
identified
as
MRID
was
submitted
to
the
Agency
in
support
of
citric
acid
as
an
active
ingredient.

Acetic
acid,
calcium
citrate,
citric
acid,
sodium
acetate,
and
sodium
citrate
have
also
been
Page
6
of
16
evaluated
by
the
Food
and
Drug
Administration
(FDA).
They
are
FDA­
affirmed
GRAS
(Generally
Regarded
As
Safe).
Calcium
acetate
is
also
FDA­
affirmed
GRAS
(21
CFR
184.1185).
Fumaric
acid
is
approved
for
use
as
a
direct
and
indirect
food
additive
"at
a
level
not
in
excess
of
the
amount
reasonably
required
to
accomplish
the
intended
effect."

International
Safety
Cards
gave
the
following
information
on
acetic
acid
(aqueous
form):
It
is
a
colorless
liquid
and
a
weak
acid.
The
substance
and
the
vapor
are
corrosive
to
the
eyes,
the
skin
and
the
respiratory
tract.
There
may
be
effects
on
the
gastrointestinal
tract.
The
TLV
(Threshold
Limit
Value)
is
25
mg/
m3
or
10
ppm.
Pure
acetic
acid
is
a
solid
below
62
o
F.
It's
most
concentrated
from
is
known
as
glacial
acetic
acid.

According
to
the
International
Safety
Cards
available
for
the
other
chemicals
discussed
in
this
document,
they
are
all
solids
(granules,
crystalline
powder
or
flakes).
No
TLVs
have
been
established.

3.
The
Citric
Acid
Cycle:

Citric
acid,
malic
acid
and
fumaric
acid
are
produced
during
the
Citric
Acid
Cycle,
which
is
also
known
as
the
Krebs
Cycle.
This
cycle
is
essential
for
the
metabolism
of
glucose
and
other
simple
sugars.
The
cycle
consists
of
a
series
of
enzymatic
chemical
reactions.
These
processes
occur
within
the
cell
and
are
responsible
for
the
final
breakdown
of
food
molecules
to
form
carbon
dioxide,
water,
and
energy.
For
risk
assessment
purposes
an
important
feature
of
this
cycle
is
that
these
acids
are
used
over
and
over
again,
thus
giving
the
body
an
effective
means
of
processing
any
ingested
citric,
fumaric,
or
malic
acid.

4.
Role
of
the
Cation
Generally,
in
dealing
with
any
acid
salt,
dissociation
yields
the
anion
from
the
acid
and
a
cation.
Generally,
concerns
for
human
and
ecological
health
would
stem
from
the
acid
moiety.
Cations
such
as
sodium,
potassium,
magnesium
and
calcium.
are
all
minerals
and
required
for
proper
functioning
of
biological
systems.
For
risk
assessment
purposes
an
important
feature
of
these
minerals
is
that
the
body
does
have
an
effective
means
of
processing
them..

Sodium
is
necessary
for
the
nerves
and
muscles
to
function
properly.
It
is
the
principal
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.

Potassium
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.

Calcium
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
Page
7
of
16
maintenance
of
cell
membranes.

Magnesium
is
also
used
in
building
bones.
It
plays
a
role
in
releasing
energy
from
muscles
and
regulating
body
temperature.
Page
8
of
16
5.

Toxicological
Profile
Table
Table
4a:

Acute
Toxicological
Profile:
acetic
acid
and
sodium
acetate
Chemical
CAS
No.

Acute
Oral
LD
50
Acute
Dermal
LD
50
Acute
Inhalation
LD
50
Skin
Irritation
Eye
irritation
Acetic
acid
64­
19­
7
LD
50
10%

solution::
3530
mg/
kg
(MRID
No.

99320)
LD
50
Rat:

3000mg/
kg
to
3800
mg/
kg
(MRID
No.

33062)
LD
50
Mice:
4400
to
5600mg/
kg
(MRID
No.

33062)
LDLo
Rabbit:
600
mg/
kg
LD
50
:

Rat
1.05mL/
kg
(MRID
No.

99320)
LDLo
Rabbit:
1060
uL/
kg
LCLo:
Rat
16000ppm/

4
hours
LD
50
Mice:
5620
ppm/
1
hour
Human:
50
mg/
24
hours:
Mild
Rabbit:
50
mg/
24
hours:
Mild
Public
literature
indicates
strong
skin
irritation
Human
skin
sensitization
has
occurred
to
concentrated
acetic
acid
Public
literature
indicates
strong
eye
irritation
Sodium
acetate
127­
09­
3
LD
50
Rat:

3500
mg/
kg
LD
50
Mouse:
4960
mg/
kg
Not
available
Not
available
Not
available
Applied
continuously
for
3
hours
to
rabbit
eyes
at
0.
1
M:

No
disturbance
of
the
cornea
Page
9
of
16
Table
4b:

Toxicological
Profile:
acetic
acid
and
sodium
acetate
Chemical
CAS
No.

Subchronic/
Chronic
Toxicity
Developmental/
Reproductive
Toxicity
Genetic
Toxicity
Other
Relevant
Information
Acetic
acid
64­
19­
7
0.

5%

acetic
acid
in
drinking
water
for
2­
4
months
reduced
the
food
intake
of
rats
(MRID
no.

33062)
Grastric
lesions
were
noted
in
rats
fed
4500
mg/
kg
acetic
acid
for
30
days.
(MRID
No..

33062)

Apple
cider
vinegar
(5%
acetic
acid)

was
administered
to
pregnant
mice,
rats,
and
rabbits
up
to
1600
mg/
kg
from
GD
6
15–
mice
and
rats;
GD
6
18–
rabbits.

No
abnormalities
were
observed
(MRID
No..

90747).

Ames
test
(With
and
without
activation;
Strains
TA100,
TA1535,
TA97,
TA98,
TA102;
Zeiger
et
al,

1992):
Negative
NIOSH
has
estimated
that
595,000
workers
are
potentially
exposued
to
acetic
acid
in
the
US
Detected
in
2/

12
human
milk
samples
(Pellizzari
et
al,
1982)
OSHA:
10
ppm
per
8
hr
duration.
NIOSH:
10
ppm
per
8
hr
duration.

15
ppm
per
15
min
duration.

50
ppm
considered
`immediately
dangerous
to
life
or
health'
FDA:

GRAS
(maximum
limits
listed
in
21CFR184.1005)
Sodium
acetate
127­
09­
3
Not
available
1.

In
vitro
studies
suggest
not
teratogenic
(ToxNet;
MRID
No.

33062)
2.

Kavlock
et
al
(1987).
CD1
mice
dosed
via
gavage
at
1000
mg/
kg/
day
from
GD8­
12.

No
adverse
effects
seen.

Sister
chromatid
exchange:
negative
Negative:
Ames
test
(With
and
without
activiation
Strains
TA1535,
TA1537,
TA1538
and
D4,

MRID
no.
33076)

FDA­

affirmed
GRAS:
21
CFR
184.1721
(not
to
exceed
current
good
manufacturing
practice)
Page
10
of
16
Table
5a:

Acute
Toxicological
Profile:
citric
acid
and
salts
Chemical
CAS
No.

Acute
Oral
LD
50
Acute
Dermal
LD
50
Acute
Inhalation
LD
50
Skin
Irritation
Eye
irritation
Citric
acid
77­
92­
9
LD
50
(mouse)
5040
mg/
kg
LDLo
(rabbit)
7000
mg/
kg
Not
available
Not
available
Rabbit:
500
mg/
24
Hours:
Miild
Rabbit:
700
ug/
24
Hours:
Severe
Calcium
citrate
7693­
13­
2
Not
available
Not
available
Not
available
Not
available
Not
available
Potassium
citrate
866­
84­
2
Sodium
citrate
68­
04­
2
(anhydrous)
6132­
04­
3
(dihydrate)
6858­
44­
2
pentahydrate

Not
available
Not
available
Not
available
Not
available
Not
available
Table
5b:

Toxicological
Profile:
citric
acid
and
salts
Chemical
CAS
No.

Subchronic/
Chronic
Toxicity
Developmental/
Reproductive
Toxicity
Genetic
Toxicity
Other
Relevant
Information
Citric
acid
77­
92­
9
Not
available
Not
available
Ames
test
(With
and
without
activation;
Strains
TA100,
TA97,
TA98,

TA104;
Al­
Ani
and
Al­

Lami
et
al,

1988):
Negative
FDA­

affirmed
GRAS:
21
CFR
184.1033
(no
limitation)
Chemical
CAS
No.

Subchronic/
Chronic
Toxicity
Developmental/
Reproductive
Toxicity
Genetic
Toxicity
Other
Relevant
Information
Page
11
of
16
Sodium
citrate
68­
04­
2
(anhydrous)
6132­
04­
3
(dihydrate)
6858­
44­
2
(penta­
hydrate)

Not
available
In
vitro
studies
suggest
not
teratogenic
Negative:
Ames
test
(With
and
without
activiation
Strains
TA97,

TA102)

FDA­

affirmed
GRAS:
21
CFR
184.1751
(no
limitation)
Potassium
citrate
866­
84­
2
Calcium
citrate
7693­
13­
2
Not
available
Not
available
Ames
test
(With
and
without
activation;
Strains
TA97,
TA98TA102
TA104;
Fujita
et
al,

1988):

Negative
FDA­

affirmed
GRAS:
21
CFR
184.1195
(no
limitation)
(may
be
used
in
infant
formula)
Page
12
of
16
Table
6a:

Acute
Toxicological
Profile:
fumaric
acid
Chemical
CAS
No.

Acute
Oral
LD
50
Acute
Dermal
LD
50
Acute
Inhalation
LD
50
Skin
Irritation
Eye
irritation
Fumaric
acid
110­
17­
8
LD
50
Rat:

6800­
10,700
mg/
kg
LD
50
Mouse:
5000
mg/
kg
LDLo
Rabbit:
5000
mg/
kg
Not
available
Not
available
Rabbit:
500
mg/
24
Hours:
Mild
Rabbit:
100
mg/
24
Hours:

Moderate
Table
6b:

Toxicological
Profile:
fumaric
acid
Chemical
CAS
No.

Subchronic/
Chronic
Toxicity
Developmental/
Reproductive
Toxicity
Genetic
Toxicity
Other
Relevant
Information
Fumaric
acid
110­
17­
8
1.

Co­

administration
with
a
naphthyridine
derivative
resulted
in
fewer
stomach
and
lung
tumors.
2.

Co­

injection
with
aflatoxin
B1
reduced
nuclear
degeneration
of
hepatocytes
3.

Tumor
inhibition
study:
1%

in
mouse
diet
for
48WK
following
88
WK
of
thioacetamide
treatment.
Reduced
incidence
In
vitro
studies
suggest
not
teratogenic
1.

Mouse
lymphoma
(with
and
without
activation):
Positive
at
2856­
8000
µg/
ml.
2.

Ames
test
(With
and
without
activiation;
Strains
TA97,
TA98,

TA100,
TA102,

TA1535)

FDA:

Direct
and
indirect
food
additive
"At
a
level
not
in
excess
of
the
amount
reasonably
required
to
accomplish
the
intended
effect."
Page
13
of
16
6.
FDA­
Sponsored
Developmental
Toxicity
Studies
These
studies
were
performed
by
the
Food
and
Drug
Research
Laboratories
in
the
1970's.
They
have
not
been
reviewed
by
the
Agency,
but
were
reported
in
the
HPV
submission.

Acetic
Acid
At
the
highest
dose
tested
(1600
mg/
kg/
day)
in
the
mouse,
the
rat,
and
the
rabbit,
there
were
no
effects
on
nidation
(fertilization),
or
on
maternal
or
fetal
survival.

Malic
Acid
At
the
only
dose
tested
(350
mg/
kg/
day)
in
the
rat,
there
were
no
treatment­
related
fetal
or
maternal
toxic
effects.
No
increases
in
fetal
malformations
were
observed.

At
the
only
dose
tested
(266
mg/
kg/
day)
in
the
mouse,
there
were
no
treatment­
related
fetal
or
maternal
toxic
effects.
No
increases
in
fetal
malformations
were
observed.

Citric
Acid
At
the
only
dose
tested
(241
mg/
kg/
day)
in
the
rat,
there
was
no
indication
of
adverse
effects
on
nidation,
maternal,
or
fetal
survival..

7.
Hazard
Characterization:

There
is
no
available
information
on
any
of
the
chemicals
considered
in
this
document
indicative
of
a
hazard,
significant
adverse
effects,
to
the
general
public
or
any
population
subgroup.
These
chemicals
are
naturally
occurring
and
are
part
of
human
metabolic
activity.

8.
Type
of
risk
assessment:
qualitative
9.
Sensitivity
of
Infants
and
Children:

These
chemicals
have
low
toxic
potential.
In
addition,
humans
of
all
ages
are
highly
exposed
to
them
from
natural
and
anthropogenic
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.

10.
Fate
and
Ecotoxicity
Assessment:
Page
14
of
16
Acetic
Acid
and
Salts
Acetic
acid
and
its
salts
undergo
dissociation
in
aqueous
media
at
pHs
commonly
found
in
the
environment
to
the
acetate
anion
and
the
respective
cations.
The
toxicity
of
each
compound
is
driven
by
the
acetate
anion
with
the
cations
paying
a
minor
role.
Data
suggest
that
acetic
acid
and
its
salts
are
not
persistent
in
the
environment.

The
available
ecotoxicity
data
indicate
that
these
compounds
are
slightly
to
practically
nontoxic
on
an
acute
basis.

Citric
Acid
and
Salts
Similarly,
citric
acid
and
its
salts
also
undergo
dissociation
in
aqueous
media
in
the
environment
to
the
citrate
anion
and
the
respective
cations.
The
toxicity
of
each
compound
is
driven
by
the
citrate
anion
with
the
cations
paying
a
minor
role.
The
available
information
indicate
that
citric
acid
and
its
trisodium
salt
are
readily
biodegraded
and
modeling
predicts
that
any
citric
acid
released
to
the
environment
would
partition
to
water.
Therefore
existing
data
indicates
that
citric
acid
and
its
salts
would
not
be
persistent
in
the
environment.

The
available
ecotoxicity
data
indicate
that
these
compounds
are
practically
nontoxic
on
an
acute
basis.

Fumaric
Acid
Fumaric
acid
is
highly
soluble
in
water
and
has
low
volatility.
Virtually
all
the
fumaric
acid
released
to
the
environment
would
partition
to
water.
Complete
biodegradation
would
take
approximately
21
days.

The
available
ecotoxicity
data
indicate
that
fumaric
acid
is
slightly
to
practically
non­
toxic
on
an
acute
basis.

Malic
Acid
Malic
acid
is
highly
soluble
in
water
and
has
a
low
volatility.
It
is
considered
to
be
readily
biodegradable
in
soil
and
water.
Modeling
predicts
that
any
citric
acid
released
to
the
environment
would
partition
to
water.
Existing
data
indicates
that
malic
acid
salts
would
not
be
persistent
in
the
environment.

Based
on
a
limited
amount
of
data
and
malic
acid's
structural
similarities
to
the
above
chemicals,
malic
acid
is
likely
to
be
practically
non­
toxic
on
an
acute
basis.

11.
Fate
and
Ecotoxicity
Characterization
Page
15
of
16
A
review
of
the
readily
available
information
on
the
chemical
substances
discussed
in
this
document
is
sufficient
to
conduct
a
qualitative
assessment
of
the
potential
exposures
and
risks
associated
with
their
use
as
pesticide
inert
ingredients.
Environmental
loadings
are
attributable
to
natural
(plants
and
animal
materials)
and
anthropogenic
(food
additives,
drugs,
and
related
products)
sources.
Available
data
indicate
that
they
rapidly
dissociate
in
the
aquatic
environment
at
environmentally
relevant
pHs
to
the
corresponding
acid
(anion)
and
its
respective
cation.
Anions
of
the
respective
compounds
undergo
aerobically
mediated
mineralization
in
days
to
weeks;
mineralization
is
complete
degradation
to
CO2
and
water.
Mobility
of
the
anions
is
expected
to
be
high
based
on
adsorption
estimates,
however,
migration
to
ground
water
should
be
substantially
mediated
through
their
rapid
biodegradation,
volatilization,
or
through
their
uptake
and
utilization
within
plant
cells.

12.
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."
The
citric
acid
cycle
chemicals
are
structurally
related;
however,
all
are
low
toxicity
chemicals.
Therefore,
the
resultant
risks
separately
and/
or
combined
should
also
be
low.
EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
these
chemicals
have
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
this
pesticide
in
a
cumulative
risk
assessment.

13.
IIFG
Recommendations:

By
consensus
there
were
no
objections
to
the
following:

The
following
tolerance
exemptions
are
reassessed:
In
40
CFR
180.2
citric
acid
and
fumaric
acid.
In
40
CFR
180.1001
(c)
acetic
acid,
calcium
citrate,
citric
acid,
potassium
citrate,
and
sodium
acetate.
In
40
CFR
180.1001
(d)
sodium
citrate.
In
40
CFR
180.1001
(e)
acetic
acid,
citric
acid,
and
potassium
citrate.

The
tolerance
exemption
for
fumaric
acid
in
40
CFR
180.1001
(d)
was
inadvertently
deleted
and
can
be
re­
established.

Additionally,
tolerance
exemptions
can
be
established
for
the
potassium,
calcium
and
magnesium
salts
of
acetic
acid
and
malic
acid.

The
following
List
reclassifications
are
made:

Acetic
acid:
Reclassified
from
List
4A
to
List
4B.
Glacial
acetic
acid
does
not
meet
the
criteria
of
Page
16
of
16
a
List
4A.
The
original
intent
was
to
establish
List
4A
classification
for
Vinegar.
Vinegar
(maximum
of
8%
acetic
acid
in
solution):
List
4A
Acetic
acid:
sodium,
potassium,
calcium,
magnesium
salts:
List
4A
Citric
acid:
List
4A,
to
harmonize
with
its
use
as
FIFRA
25(
b)
active
ingredient
Citric
acid:
sodium,
potassium,
calcium,
salts:
List
4A
Malic
acid
:
List
4A,
to
harmonize
with
its
use
as
FIFRA
25(
b)
active
ingredient
Fumaric
acid:
List
4A
based
on
its
similarities
to
malic
and
citric
acid
Attachment:

EFED
review
(Abel;
February
28,
2002)