Document ID: EPA-HQ-OPP-2005-0487-0011
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-01-25T05:00Z

Page
1
of
16
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
Documents
for
(
1)
fatty
acids
derived
from
soybean
oil,
(
2)
various
salts
of
various
fatty
acids,
(
3)
ascorbic
acid
and
ascorbyl
palmitate,
and
(
4)
isopropyl
myristate.
The
nine
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
(
4)
Page
2
of
16
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
ascorbic
acid
and
ascorbyl
palmitate.
Based
on
the
available
information
on
ascorbic
acid,
also
known
as
Vitamin
C,
and
its
role
as
an
essential
nutrient
and
its
use
as
a
food
additive,
a
qualitative
assessment
was
performed.
Based
on
the
available
information
on
ascorbyl
palmitate,
its
long
history
of
safe
use
in
cosmetics
as
an
antioxidant,
and
the
Food
and
Drug
Administration
(
FDA)
determination
of
Generally
Recognized
as
Safe
(
21
CFR
182.3149),
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
ascorbic
acid
and
ascorbyl
palmitate
from
their
uses
as
inert
ingredients
in
pesticide
products.
The
ascorbic
acid
exemption
from
the
requirement
of
a
tolerance
as
established
in
40
CFR
180.1001
(
c)
is
reassessed.
Based
on
its
lack
of
toxicity
and
its
role
as
an
essential
human
nutrient,
the
List
classification
of
ascorbic
acid
as
List
4A
is
confirmed.
The
ascorbyl
palmitate
exemptions
from
the
requirement
of
a
tolerance
as
established
in
40
CFR
180.1001
(
c)
and
(
e)
are
reassessed.
Based
on
its
overall
low
toxicity
including
its
acute
toxicity
profile
and
its
ready
biodegradation,
ascorbyl
palmitate
is
reclassified
to
List
4A
Page
3
of
16
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
25,
2003
Memorandum
Subject:
Ascorbic
Acid
and
Ascorbyl
Palmitate:
Antimicrobials
Division
Science
Assessment
Document
for
Tolerance
Reassessment.

CAS
No.:
50­
81­
7
(
Ascorbic
acid)
137­
66­
6
(
Ascorbyl
palmitate)

PC
Code.:
900395
(
Ascorbic
acid);
800155
(
Ascorbyl
palmitate)

Chemical
Class:
Ascorbic
acid
and
its
fatty
acid
ester
From:
Deborah
Smegal,
Risk
Assessor
Risk
Assessment
and
Science
Support
Branch
(
RASSB)
Antimicrobials
Division
(
7510C)

Through:
Norm
Cook,
Branch
Chief
Risk
Assessment
and
Science
Support
Branch
(
RASSB)
Antimicrobials
Division
(
7510C)

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
ascorbic
acid
and
ascorbyl
palmitate.
The
purpose
of
this
review
is
a
reassessment
of
the
exemption
from
the
requirement
of
a
tolerance.
This
assessment
summarizes
available
information
on
the
use,
physical/
chemical
properties,
toxicological
effects,
exposure
profile,
and
Page
4
of
16
environmental
fate
and
ecotoxicity
of
these
compounds.
In
performing
this
assessment,
EPA
has
utilized
reviews
previously
performed
by
EPA
and
relied
on
peer­
reviewed
evaluations
performed
by
the
Food
and
Drug
Administration
(
FDA),
Food
and
Agriculture
Organization
of
the
World
Health
Organization
(
FAO/
WHO),
and
the
Cosmetic
Ingredient
Review
(
CIR)
expert
panel.

I.
Executive
Summary:

Ascorbic
acid,
commonly
known
as
Vitamin
C,
is
a
naturally
occurring,
essential
nutrient
present
in
many
fruits
and
vegetables.
Ascorbyl
palmitate
is
an
ester
of
ascorbic
acid
with
a
long
chain
fatty
acid
(
palmitic
acid).
Ascorbic
palmitate
is
readily
metabolized
to
ascorbic
acid
in
the
human
body,
where
it
becomes
active
as
vitamin
C.
Other
significant
sources
of
exposure
include
the
many
FDA­
approved
uses
as
food
additives,
in
dietary
supplements
(
as
a
source
of
Vitamin
C),
and
cosmetic
products.
Ascorbyl
palmitate
is
a
common
ingredient
of
over
500
cosmetic
formulations,
where
is
serves
as
an
antioxidant.
Both
ascorbyl
palmitate
and
ascorbic
acid
are
classified
by
FDA
as
generally
recognized
as
safe
(
GRAS)
substances
for
the
preservation
of
foods
(
21
CFR
182.3149,
182.3013,
182.5013).

Both
ascorbyl
palmitate
and
ascorbic
acid
have
a
low
order
of
oral
and
dermal
toxicity.
Ascorbic
acid
did
not
produce
adverse
developmental,
reproductive
or
carcinogenic
effects
in
animals.
Both
compounds
have
numerous
beneficial
effects,
and
a
deficiency
in
ascorbic
acid
causes
scurvy.

Ascorbic
acid
is
naturally
present
in
all
aquatic
and
biotic
systems;
it
is
essential
to
animal
life
and
is
naturally
synthesized
by
most
plants,
but
not
invertebrates,
or
fish.
It
is
essential
for
normal
growth
and
development,
and
thus
is
present
in
the
majority
of
living
organisms.
Ascorbic
acid
is
widely
used
as
a
dietary
supplement
in
fish
and
chicken
reared
for
food
production.
The
available
ecotoxicity
data
for
ascorbyl
palmitate
indicate
that
it
may
be
more
toxic
than
ascorbic
acid.
However,
based
on
its
physical/
chemical
properties,
ascorbyl
palmitate
has
low
water
solubility
and
is
expected
to
have
moderate
to
strong
sorption
to
soils
and
sediments,
fairly
rapid
microbial
degradation,
and
negligible
migration
to
surface
water
and
groundwater.
Thus,
it
is
unlikely
to
result
in
significant
risk.

Based
on
available
information
on
ascorbic
acid
and
ascorbyl
palmitate,
their
expected
use
patterns,
their
safe
history
of
use
a
food
additives,
their
extensive
use
in
commercially­
available
cosmetics
and
their
low
toxicity,
the
Lower
Toxicity
Pesticide
Chemical
Focus
Group
has
determined
that
a
quantitative
risk
assessment
is
not
required
for
these
compounds.

II.
Use
Information:

The
tolerance
exemptions
being
reassessed
in
this
document,
the
associated
40
CFR
location,
and
the
use
pattern
as
an
inert
ingredient
are
listed
in
Table
1.
Page
5
of
16
Table
1
Tolerance
Exemptions
Being
Reassessed
in
this
Document
Tolerance
Exemption
Expression
Inert
PC
Code
Cas
No.
40
CFR
180.1001
List
Classification
Use
Pattern
(
Pesticidal)

ascorbic
acid
900395
50­
81­
7
(
c)
4A
stabilizer,
preservative
ascorbyl
palmitate
800155
137­
66­
6
(
c)
3
preservative
in
formulations
applied
to
growing
crops
(
e)
preservative
in
formulations
applied
to
animals
Ascorbic
acid
(
Vitamin
C):
Ascorbic
acid
is
classified
as
a
GRAS
substance
by
FDA
as
a
food
additive
permitted
for
direct
addition
to
food
for
human
consumption
when
used
as
a
preservative
and
nutrient
and/
or
dietary
supplement
(
vitamin
C
supplement)
(
21
CFR
182.3013
and
182.5013,
respectively).
Ascorbic
acid
is
also
approved
as
a
dough
conditioner
in
cereal
flours
(
tolerance
200
ppm),
breads
and
other
bakery
products
(
21
CFR
136
and
137);
as
an
acidulant
in
frozen
desserts
(
21
CFR
135);
as
a
preservative
in
artificially
sweetened
fruit
jellies
and
preserves
(
21
CFR
150);
and
as
an
optional
ingredient
in
canned
artichokes
and
mushrooms
(
21
CFR
155.200).
It
is
an
inhibitor
of
enzymatic
browning
or
as
preservatives
(
antioxidants)
in
a
variety
of
foods
and
beverages
including
concentrated
milk
products,
certain
meat
products,
pickling
brine
for
pork
and
beef
cuts,
baked
goods,
soft
and
hard
candies,
fats,
and
oils,
gravies,
breakfast
cereals
and
processed
fruits
and
vegetables
(
FDA
1979).

Ascorbic
acid
is
also
approved
by
the
U.
S.
Department
of
Agriculture
(
USDA)
as
curing
accelerators
for
pork
and
beef
and
comminuted
meat
products
(
9CFR
318.7
(
c)
(
4))
(
FDA
1979).
It
is
also
used
as
a
dietary
supplement
in
animal
feed
(
SIDS
2003).

Acorbic
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
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
rightto
know
about
the
potential
hazards
of
chemicals
found
in
their
environment,
their
homes,
their
workplace,
and
in
consumer
products.

Ascorbyl
palmitate:
Ascorbyl
palmitate
is
also
classified
as
a
GRAS
substance
by
FDA
as
a
food
preservative
(
21
CFR
182.3149).
It
is
a
natural
and
synthetic
food
antioxidant
that
prevents
rancidity
and
the
browning
of
cut
apples.
In
addition
to
its
use
as
a
food
preservative,
it
Page
6
of
16
is
an
antioxidant
in
pharmaceuticals,
a
source
of
vitamin
C,
a
stabilizer
and
emulsifier,
and
is
used
in
medications
(
Toxnet
2003).
Ascorbyl
palmitate
is
a
common
ingredient
of
over
500
cosmetic
formulations,
where
it
serves
as
an
antioxidant.
It
is
used
at
concentrations
between
0.01
and
0.2%
in
these
products
(
CIR
1997).

Table
2:
Use
Pattern
(
FDA
GRAS)

Chemical
GRAS
Citation
GRAS
Uses
ascorbyl
palmitate
21
CFR
182.3149
preservative
in
foods
ascorbic
acid
21
CFR
182.3013
preservative
in
foods
ascorbic
acid
21
CFR
182.5013
nutrient
and/
or
dietary
supplement
III.
Physical/
Chemical
Properties:

The
physical/
chemical
properties
of
ascorbic
acid
and
ascorbyl
palmitate
are
shown
on
Table
3.

Table
3
Physical/
Chemical
Properties
Parameter
Ascorbic
Acid
Ascorbyl
Palmitate
Molecular
formula
C6H8O6
C22H38O7
Melting
point
190­
192
C
116
C
Solubility
in
water
(
mg/
L)
0.33;
freely
soluble
at
20oC
0.06;
slightly
soluble
Molecular
Weight
176.12
414.54
Physical
state
colorless
crystals
or
white
or
yellowish
white
crystalline
powder
white
or
yellowish
white
powder
Log
Kow
­
1.85,
experimental
6,
experimental
Vapor
pressure
(
mmHg)
1.79E­
10
4.5E­
17,
experimental
(
25o
C)

Henry's
Law
constant
(
atmm3
mole)
4.07E­
08
4.3E­
17,
experimental
Koc
10
247
(
25o
C)

LogBCF
0.5
2.73,
estimated
Page
7
of
16
Ascorbic
Acid
Ascorbyl
Palmitate
IV.
Hazard
Assessment:

The
key
toxicological
data
in
the
following
sections
were
obtained
from
ToxNet
(
www.
toxnet.
nlm.
nih.
gov)
and
other
websites,
such
as
FirstGov
(
www.
firstgov.
gov),
as
well
as
from
the
Cosmetic
Ingredient
Review
(
CIR)
safety
assessment,
FDA
GRAS
assessments,
Food
and
Agriculture
Organization
of
the
World
Health
Organization
(
FAO/
WHO)
evaluations,
and
Structure­
Activity
Relationship
(
SAR)
assessments.

Ascorbic
palmitate
is
an
ester
of
ascorbic
acid,
having
greater
fat
solubility
because
of
the
long
chain
fatty
acid
(
palmitic
acid).
It
is
readily
metabolized
to
ascorbic
acid
in
the
gastrointestinal
tract,
where
it
becomes
active
as
Vitamin
C
(
FDA
1979).
The
FDA
concluded
that
ascorbyl
palmitate
has
vitamin
C
activity
that
is
nearly
equivalent
to
that
of
L­
ascorbic
acid,
the
most
potent
of
four
ascorbic
acid
stereoisomers
(
FDA
1979).

In
the
sections
below,
the
available
toxicological
data
for
ascorbyl
palmitate
and
ascorbic
acid
via
the
oral,
dermal
and/
or
inhalation
routes
of
exposure
are
summarized.

A.
Toxicological
data
available
for
ascorbyl
palmitate:

As
noted
previously,
ascorbyl
palmitate
is
classified
by
FDA
as
a
GRAS
substance
as
a
preservative
in
foods
(
21
CFR
182.3149).
It
also
has
extensive
use
in
cosmetics.
A
Cosmetic
Ingredient
Review
(
CIR)
safety
assessment
of
ascorbyl
palmitate
reviewed
acute
oral,
dermal,
skin
irritation,
chronic,
carcinogenicity,
and
mutagenicity
studies.
This
expert
panel
concluded
that
it
is
"
safe
for
use
as
cosmetic
ingredients
in
the
present
practices
of
use."
The
use
concentration
of
the
ascorbyl
palmitate
in
cosmetic
products
varies
from
0.01
to
0.2
percent
(
CIR
1997).
1
There
are
differences
in
dose
estimates
for
this
study.
EPA
has
estimated
0.05%,
0.25%
and
5%
to
be
equivalent
to
doses
of
71,
357
and
7142
mg/
kg/
day,
respectively
based
on
the
following
equation:
mg/
kg
food*
kg
food/
day
*
1/
body
wt
(
kg)
=
mg/
kg/
day
where
0.25%
=
2500
mg/
kg,
and
kg
food/
day
=
0.05
and
body
weight
for
rats=
0.35
kg.
WHO
1974
estimated
that
0.25%
was
equivalent
to
125
mg/
kg/
day.
CIR
1997
estimated
0.05%
and
0.25%
were
equivalent
to
424
and
1060
mg/
kg/
day.
FDA
1979
estimated
that
0.25%
ascorbyl
palmitate
is
equivalent
to
about
53
mg/
kg
ascorbic
acid.

Page
8
of
16
The
FDA
evaluated
the
toxicological
data
for
ascorbic
acid
and
ascorbyl
palmitate
(
FDA
1979)
and
concluded
"
there
is
no
evidence
in
the
available
information
on
L­
ascorbic
acid,
sodium
L­
ascorbate,
calcium
L­
ascorbate,
ascorbyl
palmitate
(
palmitoyl
L­
ascorbate),
...
that
demonstrates,
or
suggests
reasonable
grounds
to
suspect,
a
hazard
to
the
public
when
they
are
used
as
food
ingredients
at
levels
that
are
now
current
or
that
might
reasonably
be
expected
in
the
future."

The
Joint
FAO/
WHO
Expert
Committee
on
food
additives
(
1974)
has
evaluated
ascorbyl
palmitate
and
estimated
an
acceptable
daily
intake
(
ADI)
for
man
of
between
0­
1.25
mg/
kg.
The
ADI
was
based
on
an
evaluation
of
several
animal
toxicity
studies,
and
a
no­
observed
adverse
effect
level
of
2500
ppm
(
0.25%
diet).

Ascorbyl
palmitate
has
a
low
order
of
acute
oral
and
dermal
toxicity
in
animal
studies.
In
rats,
the
lowest
acute
effect
level
was
2500
mg/
kg/
day,
which
caused
a
decrease
in
body
weight
(
FDA
1995
as
cited
in
CIR
1997).
The
acute
oral
LD
50
for
a
33%
suspension
of
ascorbyl
palmitate
in
mice
is
2
g/
kg.
The
acute
dermal
LD
50
in
guinea
pigs
was
>
3
g/
kg
(
SCC
1993
as
cited
in
CIR
1997).
Ascorbyl
palmitate
(
10%)
was
not
irritating
to
the
intact
skin
of
albino
rabbits,
nor
did
it
not
cause
eye
irritation
in
albino
rabbits
(
CIR
1997).
In
clinical
studies
to
assess
cosmetic
safety,
ascorbyl
palmitate
did
not
cause
dermal
irritation
or
sensitization
(
CIR
1997).

Ascorbyl
palmitate
penetrates
the
skin
readily.
When
applied
topically
to
guinea
pigs,
ascorbyl
palmitate
penetrated
the
skin
barrier
so
that
ascorbic
acid
content
in
skin,
liver
and
blood
increased
by
8­,
7­
and
4­
fold,
respectively
compared
to
controls
(
Koroleva
et
al.
1981
as
cited
in
CIR
1997).

There
are
a
few
longer­
term
animal
toxicological
studies
available
for
ascorbyl
palmitate.
In
a
nine­
month
and
two­
year
study
conducted
by
the
same
researchers,
rats
(
n=
10/
group)
were
fed
heat­
treated
lard
containing
dietary
concentrations
of
2
or
5%
L­
ascorbyl
palmitate
(
0.05%
or
0.25%
of
the
total
diet)
1.
In
the
nine­
month
study,
growth
rate
was
significantly
retarded
at
the
5%
level,
and
two
of
the
ten
rats
had
numerous
bladder
stones
and
hyperplasia
of
the
bladder
epithelium.
Another
rat
in
this
group
had
an
inflammatory
condition
in
the
kidney.
There
was
a
slight
retardation
of
growth
in
the
2%
dietary
group,
but
there
were
no
significant
differences
for
mortality
or
histopathology
(
Fitzhugh
and
Nelson
1946
as
cited
in
FAO/
WHO
1974).
In
the
two
year
study,
however,
no
adverse
effects
were
noted
for
growth
rate,
mortality,
and
pathological
examination
(
Fitzhugh
and
Nelson
1946
as
cited
in
FAO/
WHO
1974
and
FDA
1979,
SCC
1993
as
cited
in
CIR
1997).
The
Joint
FAO/
WHO
Expert
Committee
concluded
that
the
bladder
stone
formation
noted
in
this
study
is
not
relevant
for
humans.
Page
9
of
16
In
a
study
to
evaluate
the
carcinogenic
potential
of
ascorbyl
palmitate,
mice
were
given
dietary
concentrations
of
0
or
2%
ascorbyl
palmitate
for
two
weeks,
and
then
given
azoxymethanol
(
which
induces
the
formation
of
focal
areas
of
dysplasia
(
FAD))
or
saline.
Ascorbyl
palmitate
did
not
produce
signs
of
toxicity
or
effect
body
weight.
No
focal
areas
of
dysplasia
were
observed
in
control
mice
or
those
fed
ascorbyl
palmitate
(
Huang
et
al.
1992
as
cited
in
CIR
1997).

Ascorbyl
palmitate
was
not
mutagenic
in
the
Ames
assay
using
S.
typhimurium
(
Ames
test)
and
E.
Coli.
(
tryptophan
reversion
assay
)
(
Prival
et
al.
1991
as
cited
in
CIR
1997).

Beneficial
Effects:
Ascorbyl
palmitate
has
been
reported
to
have
beneficial
pharmacological
effects.
It
appeared
to
prevent
liver
damage
induced
by
acetaminophen
in
mice,
by
removing
the
reactive
acetaminophen
metabolite
and
by
having
a
sparing
action
on
reduced
hepatic
glutathione
(
Jonker
et
al.
1988
as
cited
in
CIR
1997).
Small
topical
doses
of
ascorbyl
palmitate
inhibited
by
91%
of
tumors
in
previously
initiated
mice,
It
also
inhibited
12­
Otetradecanoylphorbol
13­
acetate
(
TPA)­
induced
ornithine
decarboxylase
activity,
tumor
production
and
DNA
synthesis
in
mouse
epithelial
cells
(
Smart
et
al.
1987
as
cited
in
CIR
1997).

B.
Ascorbic
Acid
Ascorbic
acid,
or
vitamin
C,
is
a
naturally
occurring,
essential
nutrient
present
in
many
edible
plants,
especially
rapidly
growing
leafy
vegetables,
fruits,
tomatoes
and
potatoes
(
FDA
1979).
It
is
synthesized
in
most
plants
and
by
many
animals,
but
not
by
man,
primates,
and
certain
species
such
as
the
fruit
bat
and
guinea
pig.
Species
that
do
not
naturally
synthesize
ascorbic
acid
must
obtain
it
from
the
diet
(
SIDS
2003).
The
average
per
capita
consumption
in
the
U.
S.
has
been
estimated
to
be
213
mg/
day
for
individuals
2
years
of
age
and
older
(
FDA
1979).
The
total
body
store
of
ascorbic
acid
in
a
healthy
human
adult
is
estimated
to
be
about
1.5
g
(
or
approximately
21
mg/
kg
for
a
70
kg
individual).
The
U.
S.
Recommended
Daily
Allowance
(
RDA)
is
60
mg/
day
for
adults
and
children
>
4
years
of
age
(
Rumack
2003
as
cited
in
Toxnet
2003).
Some
scientists
have
concluded
that
oral
doses
up
to
10
g/
day
ascorbic
acid
do
not
constitute
a
health
risk
(
Counsell
and
Hornig
1981
as
cited
in
SIDS
2003).
Three
individuals
administered
a
1
g
daily
supplement
of
ascorbic
acid
for
3
months
did
not
experience
harmful
effects
(
Lowry
et
al.
1952
as
cited
in
FDA
1979).
Individuals
occupationally
exposed
to
up
to
10
mg/
m3
ascorbic
acid
(
8
hour
time­
weighted
average)
did
not
exhibit
any
adverse
health
effects
(
SIDS
2003).

Ascorbic
acid
is
essential
for
the
proper
functioning
of
all
cellular
units
in
higher
plants
and
animals,
and
in
the
synthesis
of
collagen.
A
severe
deficiency
of
ascorbic
acid
causes
scurvy
(
when
the
body
reservoir
falls
below
300
mg).
This
is
characterized
by
lassitude,
joint
tenderness,
swollen
and
inflamed
gums,
anemia,
capillary
hemorrhages,
failure
of
wounds
to
heal,
and
failure
of
the
cartilage,
bone,
and
dentine
to
develop
normally.
It
has
several
biochemical
roles,
including
acting
as
a
reducing
agent,
promoting
iron
absorption,
and
breaking
down
cholesterol
to
bile
acids
(
FDA
1979).
Page
10
of
16
As
noted
previously,
ascorbic
acid
is
classified
by
the
FDA
as
a
GRAS
substance.
It
has
a
history
of
safe
use
as
natural
components
of
many
foods,
as
direct
food
additives,
and
as
cosmetic
ingredients.
The
FDA
evaluated
the
toxicological
data
for
ascorbic
acid
and
ascorbyl
palmitate
(
FDA
1979)
and
concluded
"
there
is
no
evidence
in
the
available
information
on
L­
ascorbic
acid,
sodium
L­
ascorbate,
calcium
L­
ascorbate,
ascorbyl
palmitate
(
palmitoyl
L­
ascorbate),
...
that
demonstrates,
or
suggests
reasonable
grounds
to
suspect,
a
hazard
to
the
public
when
they
are
used
as
food
ingredients
at
levels
that
are
now
current
or
that
might
reasonably
be
expected
in
the
future."

Ascorbic
acid
is
practically
non­
toxic
based
on
acute
oral
toxicity
studies
in
rats,
mice,
guinea
pigs,
and
dogs
(
LD
50
>
5
g/
kg)
(
FDA
1979,
SIDS
2003).
Subchronic
oral
toxicity
data
for
several
different
animal
species
also
indicate
its
low
toxicity;
the
mouse
10­
day
LD
50
is
8021
mg/
kg,
the
rat
6­
day
LD
50
is
>
6500
mg/
kg,
the
guinea
pig
6­
day
LD
50
is
>
8900
mg/
kg,
and
the
dog
7­
day
LD
50
is
100
mg/
kg
(
FDA
1979).
L­
Ascorbic
acid
did
not
cause
dermal
irritation
in
rabbits
when
applied
to
the
intact
and
abraded
skin
under
semi­
occlusive
conditions
for
4
hours.
It
is
non­
irritating
to
the
rabbit
eye
(
Roche
Research
Report
as
cited
in
SIDS
2003).
Ascorbic
acid
(
30%
aqueous
solution)
did
not
produce
dermal
sensitization
in
guinea
pigs
(
SCC
1993
as
cited
in
CIR
1997).

No
harmful
effects
were
noted
in
rats
following
the
oral
administration
of
6.5
g/
kg
over
a
10
week
period.
However,
daily
doses
of
27.3
g/
kg
were
toxic;
the
mortality
rate
rose
to
77%
within
4
weeks.
The
investigators
concluded
that
the
maximum
nontoxic
dose
in
the
rat
is
10
g/
kg
(
FDA
1979).
In
another
short­
term
study,
weight
gain
in
young
rats
was
reduced
as
doses
above
1
g/
kg
ascorbic
acid.
A
laxative
effect
was
noted
in
rats
that
received
10
g/
kg,
and
two
of
six
rats
in
this
group
died.

In
a
developmental
study,
pregnant
rats
(
n=
19­
27)
were
given
150,
250,
500
and
1000
mg/
kg/
day
ascorbic
acid
from
gestational
days
6­
15
in
the
first
trial
and
from
postconception
days
0­
21
for
the
second
trial.
Mice
(
n=
19­
27)
also
received
oral
daily
doses
of
250,
500,
or
1000
mg/
kg
ascorbic
acid
from
days
6­
15
of
pregnancy.
There
were
no
indications
of
parental
toxicity,
or
teratogenic
or
fetotoxic
effects.
There
was
no
apparent
effect
on
the
embryonic
and
postpartum
development
of
the
young
or
on
breeding
behavior,
pregnancy,
parturition,
and
lactation
capacity
of
the
dams
(
Frohberg
et
al.
1973
as
cited
in
FDA
1979
and
SIDS
2003).
In
other
developmental
studies,
ascorbic
acid
was
given
at
doses
up
to
520
mg/
kg
to
pregnant
mice
and
up
to
550
mg/
kg
to
pregnant
rats
for
10
consecutive
days
starting
on
day
6.
No
discernable
effects
were
noted
on
maternal
or
fetal
survival,
or
soft
tissue
or
skeletal
abnormalities
(
Food
and
Drug
Research
Laboratories
1975
as
cited
in
FDA
1979).

In
a
reproductive
study
with
guinea
pigs,
initiation
and
maintenance
of
pregnancy
was
less
successful
in
animals
given
4
mg/
kg
ascorbic
acid
compared
to
those
given
10
and
100
mg/
kg.
The
offspring
of
the
parent
animals
given
100
mg/
kg
had
a
reduced
survival
rate
(
Steel
1969,
as
cited
in
FDA
1979).
In
another
study,
diets
up
to
500
mg/
kg
ascorbic
acid
fed
to
guinea
pigs
did
not
adversely
affect
the
number
and
size
of
the
litters
or
any
other
aspect
of
fertility
(
Korner
and
2Estimated
doses
based
on
the
following:
mg/
kg
food*
kg
food/
day
*
1/
body
wt
(
kg)
=
mg/
kg/
day
where
2.5%
=
25,000
mg/
kg,
and
kg
food/
day
=
0.05
(
rats)
and
0.13
(
mice)
and
body
weight
of
0.35
kg
(
rats)
and
0.03
kg
(
mice).

Page
11
of
16
Weber
1972
as
cited
in
FDA
1979).
In
a
third
reproductive
study,
guinea
pigs
were
fed
1.5,
4
or
100
mg
ascorbic
acid
for
three
generations.
The
high
dose
group
had
the
most
litters
and
fewest
abortions,
but
there
were
no
differences
among
the
groups
in
the
number
of
newborns
or
viable
young
(
Rivers
1974
as
cited
in
FDA
1979).

In
a
10
month
rat
study,
20
g/
kg
L­
ascorbic
acid
increased
urinary
oxalate,
calcium
and
iron,
but
had
no
significant
effect
on
calcification
in
the
kidneys
nor
did
it
affect
the
kidney
calcium
concentration.
There
were
no
other
adverse
effects
reported
(
Keith
et
al.
1974
as
cited
in
SIDS
2003).

In
a
2
year
chronic
study,
groups
of
26/
sex
rats
were
fed
doses
of
0,
1,
1.5
or
2
g/
kg/
day
ascorbic
acid.
There
were
no
treatment­
related
effects
for
body
weight,
mortality,
general
physical
condition,
blood
and
urine
chemistry,
liver
and
kidney
function
tests,
or
macro­
and
micropathological
appearance
of
the
various
organs
and
tissues
examined
(
FDA
1979).

In
a
more
recent
2­
year
chronic
study,
rats
and
mice
(
n=
50/
sex/
dose)
fed
dietary
concentrations
of
2.5
and
5%
(
equivalent
to
approximately
3.6
and
7.1
g/
kg/
day
for
rats,
and
108
and
217
g/
kg/
day
for
mice,
respectively)
2
did
not
exhibit
treatment
related
clinical
signs
other
than
slight
lowering
of
mean
body
weight
in
female
mice
and
rats.
There
was
no
evidence
of
carcinogenicity
(
Douglas
et
al.
1984
as
cited
in
SIDS
2003).

The
weight
of
evidence
indicates
that
L­
ascorbic
acid
does
not
produce
gene
mutation
in
Samonella
typhimurium
or
Saccharomyces
cerevisiae,
nor
in
mammalian
cells
using
the
mouse
lymphoma
assay
(
L5178Y
TK
+/­
cell).
L­
Ascorbic
acid
has
no
structural
alerts
for
alkylation.
Positive
results
were
consistently
obtained
in
vitro
assays
for
sister
chromatid
exchange
(
SCE)
and
unscheduled
DNA
synthesis
(
UDS)
induction
with
and
without
metabolic
activation,
indicating
the
ability
to
produce
DNA
damage
under
certain
conditions.
However,
negative
results
were
obtained
in
in
vivo
assays,
using
high
dose
levels,
for
the
induction
of
micronclei
and
SCEs
in
bone
marrow
chinese
hamsters.
Although
activity
was
seen
in
in
vitro
assays
for
genotoxicity
(
UDS
and
SCEs)
the
mechanism
involved
would
suggest
that
activity
was
unlikely
to
be
seen
in
vivo.
It
has
been
postulated
that
the
mammalian
organism
is
protected
against
damage
by
peroxide
radicals
or
that
such
radicals
are
not
formed
by
L­
ascorbic
acid
in
body
fluid.
Thus,
L­
ascorbic
acid
is
not
an
in
vivo
mutagen
(
SIDS
2003).

In
animals,
such
as
guinea
pigs
and
rats,
the
major
product
of
metabolism
is
carbon
dioxide,
which
is
excreted
in
the
lungs.
Urinary
and
fecal
excretion
contribute
only
a
minor
part.
The
metabolism
of
L­
ascorbic
acid
in
the
monkey
and
man
are
similar.
Half­
lives
are
substantially
prolonged
when
lower
amounts
of
L­
ascorbic
acid
are
ingested.
The
percentage
of
unmetabolized
L­
ascorbic
acid
excreted
in
urine
increases
with
the
dietary
intake.
In
the
monkey
Page
12
of
16
and
man,
L­
ascorbic
acid
is
not
primarily
converted
to
carbon
dioxide,
but
rather
is
excreted
as
ascorbate
and
oxalate
in
the
urine
(
SIDS
2003).

Beneficial
Effects:
Many
studies
suggest
that
substantial
intakes
of
ascorbic
acid
generally
diminish
the
toxicity
of
(
i.
e.,
provide
protection
against)
the
excesses
of
several
heavy
metals,
including
lead,
mercury,
vanadium
and
cadmium
(
FDA
1979).
Ascorbic
acid
has
also
been
shown
to
promote
the
absorption
of
iron
in
individuals
(
FDA
1979).
In
addition,
topical
application
of
10%
vitamin
C
to
pigs
protected
the
skin
against
ultraviolet
B
(
UVB)
damage
(
CIR
1997).
It
has
been
suggested
that
ascorbic
acid
is
useful
in
the
prevention
and
treatment
of
the
common
cold
and
other
disorders
(
FDA
1979).

D.
Special
Considerations
for
Infants
and
Children
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.

V.
Exposure
Assessment:

The
most
significant
source
of
exposure
to
ascorbic
acid
is
the
diet.
L­
Ascorbic
acid
is
naturally
occurring
in
many
foodstuffs
at
levels
ranging
from
40
mg/
kg
in
apples
to
20,000
mg/
kg
in
acerola
cherries.
Parsley,
green
peppers,
lemons,
oranges,
tomatoes,
potatoes
and
mushrooms
are
other
sources
of
L­
ascorbic
acid.
Other
significant
sources
of
exposure
include
the
many
FDA­
approved
uses
as
food
additives,
in
dietary
supplements
(
as
a
source
of
Vitamin
C),
and
cosmetic
products.
As
noted
previously,
ascorbyl
palmitate
is
a
common
ingredient
of
over
500
cosmetic
formulations,
where
is
serves
as
an
antioxidant.
It
is
used
at
concentrations
between
0.01
and
0.2%
in
these
products
(
CIR
1997).
For
example,
it
is
present
at
0.02%
in
body
cleansers,
0.02%
in
cologne,
at
0.01%
in
body
oil,
and
at
0.2%
in
eye
cream.

The
total
body
store
of
ascorbic
acid
in
a
healthy
human
adult
is
estimated
to
be
about
1.5
g
(
or
approximately
21
mg/
kg
for
a
70
kg
individual).
The
U.
S.
RDA
is
60
mg/
day
for
adults
and
children
>
4
years
of
age
(
Rumack
2003
as
cited
in
Toxnet
2003).

Residues
from
the
pesticide
uses
of
ascorbic
acid
and
ascorbyl
palmitate
are
not
likely
to
exceed
the
naturally
occurring
levels
of
ascorbic
acid
in
commonly
eaten
foods.
In
addition,
the
use
of
these
compounds
in
pesticide
products
is
expected
to
result
in
much
lower
exposure
than
the
FDA­
regulated
use
of
these
compounds,
as
well
as
lower
exposure
than
the
use
in
cosmetics.
For
example,
cosmetic
products
containing
ascorbyl
palmitate
may
be
used
from
once
a
week
up
to
several
times
a
day,
and
may
remain
in
contact
with
body
surfaces
for
a
few
minutes
(
hair
bleachers,
cleansing
creams)
to
as
long
as
a
few
days
(
moisturizing
creams)
(
CIR
1997).
Both
ascorbic
and
ascorbyl
palmitate
are
of
low
toxicity
to
humans,
and
there
is
no
reason
to
expect
that
reasonable
use
will
constitute
any
significant
hazard.
Therefore,
a
quantitative
screeninglevel
exposure
assessment
has
not
been
conducted.
Page
13
of
16
VI.
Risk
Characterization:

Ascorbyl
palmitate
is
readily
metabolized
to
ascorbic
acid
in
the
human
body,
and
ascorbic
acid,
is
a
significant
part
of
the
normal
daily
diet.
As
previously
discussed
in
this
document,
there
are
many
FDA
approved
uses.
Residues
from
the
pesticide
uses
of
ascorbyl
palmitate
and
ascorbic
acid
are
not
likely
to
exceed
the
naturally
occurring
levels
in
commonly
eaten
foods,
or
the
current
exposures
from
FDA­
approved
uses.

Taking
into
consideration
all
available
information
on
ascorbyl
palmitate
and
ascorbic
acid,
including
their
low
acute
toxicity
via
oral
and
dermal
routes,
FDA's
designation
of
both
compounds
as
GRAS,
their
presence
in
food
products,
food
additives,
and
cosmetics,
as
well
as
the
significant
contribution
of
ascorbic
acid
(
vitamin
C)
in
the
diet,
the
uses
of
these
compounds
as
inert
ingredients
in
pesticide
products
are
unlikely
to
pose
a
significant
hazard
to
the
general
public
or
any
population
subgroup.
Exposures
from
the
aforementioned
uses
are
expected
to
result
in
human
exposure
below
any
dose
level
that
could
possibly
produce
an
adverse
effect.
As
a
result,
AD
is
conducting
a
qualitative
approach
to
assessing
human
health
risks
from
exposure
to
ascorbyl
palmitate
and
ascorbic
acid.

As
noted
previously,
ascorbic
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
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.
Based
on
the
available
toxicity
data
for
ascorbic
acid,
the
Agency
feels
confident
in
proceeding
with
this
tolerance
reassessment
decision.
Any
submission
of
data
for
ascorbic
acid
as
part
of
the
HPV
Challenge
Program
may,
in
the
future,
be
used
by
OPP
to
revise
or
update
their
tolerance
reassessment
decision
for
ascorbic
acid
as
deemed
necessary
and
appropriate.

VII.
Environmental
Fate/
Ecotoxicity/
Drinking
Water
Considerations:

Environmental
Fate
Characterization
Ascorbyl
Palmitate.
Based
on
its
physical/
chemical
properties,
ascorbyl
palmitate
is
slightly
soluble
in
water
and
is
expected
to
have
moderate
to
strong
sorption
to
soils
and
sediments.
Therefore,
there
is
limited
potential
to
reach
surface
water
by
dissolved
runoff
and/
or
leach
to
ground
water
(
EPA
1995).
Volatilization
from
soils
and
water
is
not
likely
to
be
an
important
transport
process
in
the
environment
based
on
ascorbyl
palmitate's
low
vapor
pressure
and
Henry's
law
constant.
Although
there
is
potential
to
bioaccumulate
(
log
Kow
6),
bioavailability
is
offset
by
rapid
primary
biodegradation
(
hours
to
days).
Page
14
of
16
Ascorbic
Acid.
Ascorbic
acid
is
freely
soluble
in
water.
L­
Ascorbic
acid
degraded
11%
after
7
days
and
50%
after
28
days.
Degradation
was
more
rapid
in
the
presence
of
activated
sludge,
where
L­
ascorbic
acid
(
733
mg/
L)
biodegraded
by
97%
after
5
days
and
completely
after
15
days.
There
is
no
evidence
that
ascorbic
acid
bioaccumulates
in
animals
or
man.
There
was
no
bioaccumulation
in
guinea
pigs
fed
86
g/
kg
ascorbic
acid
for
275
days
(
SIDS
2003).

Ecotoxicity
and
Ecological
Risk
Characterization
Ascorbyl
Palmitate.
The
limited
ecotoxicity
data
show
that
ascorbyl
palmitate
is
moderately
to
fish
(
96­
hour
LC
50
=
0.45­
1.2
ppm),
and
highly
toxic
to
Daphnia
magna
(
48­
hour
EC
50
=
0.07­
0.36
ppm),
and
green
algae
(
96­
hr
EC
50
=
0.04
ppm)
(
EPA
2002,
EFED
memo).
The
chronic
toxicity
estimate
for
fish
is
0.003
ppm.
However,
the
water
solubility
of
0.06
ppm
is
less
than
the
fish
96­
hr
LC
50
.
Considering
this
factor
and
in
combination
with
the
very
low
mobility
and
bioavailability,
there
is
less
potential
for
acute
risk
to
fish
than
for
the
free
acid
groups.
Aquatic
invertebrates
will
be
at
a
greater
acute
risk
than
fish,
nevertheless
the
greatly
reduced
bioavailability
and
fairly
rapid
microbial
degradation 
approximately
4
days
for
primary
degradation 
will
not
likely
result
in
significant
risk
(
EPA
2002,
EFED
memo).

A
Structure
Activity
Relationship
(
SAR)
assessment
for
ascorbyl
palmitate
predicted
that
this
compound
may
be
more
toxic
than
ascorbic
acid.
However,
based
on
its
physical/
chemical
properties,
ascorbyl
palmitate
is
expected
to
have
moderate
to
strong
sorption
to
soils
and
sediments,
and
negligible
migration
to
groundwater
(
EPA
1995,
EPA
2002,
EFED
memo).

Ascorbic
Acid.
L­
Ascorbic
acid
is
naturally
present
in
all
aquatic
and
biotic
systems;
it
is
essential
to
animal
life
and
is
naturally
synthesized
by
most
plants,
but
not
invertebrates,
or
fish.
It
is
essential
for
normal
growth
and
development,
and
thus
is
present
in
the
majority
of
living
organisms.
L­
Ascorbic
acid
levels
in
plants
are
typically
in
the
range
of
200­
500
mg/
kg
(
SIDS
2003).
L­
ascorbic
acid
is
widely
used
as
a
dietary
supplement
in
fish
and
chicken
reared
for
food
production.
No
adverse
effects
were
noted
in
developing
hatchlings
of
trout
(
n=
300)
and
catfish
(
n=
60)
fed
dietary
levels
as
high
as
10
g/
kg
and
5
g/
kg
for
16
and
21
weeks,
respectively
(
Lann
et
al.
1985,
Mayer
et
al.
1978,
respectively
as
cited
in
SIDS
2003).
These
concentrations
are
approximately
100
times
the
normal
requirement
for
healthy
growth
and
wound
healing
in
trout
and
catfish,
which
are
100
mg/
kg
and
60
mg/
kg,
respectively
(
Vitamin
Tolerance
of
Animals,
National
Academy
Press
1987
as
cited
in
SIDS
2003).
In
chickens,
dietary
concentrations
up
to
3.3
g/
kg
for
up
to
30
weeks
had
no
adverse
effects
(
Chen
and
Nockels
1973
as
cited
in
SIDS
2003).

L­
Ascorbic
acid
has
low
toxicity
to
rainbow
trout.
In
a
96
hour
acute
toxicity
study,
rainbow
trout
(
n=
10/
group)
were
exposed
to
L­
ascorbic
acid
concentrations
of
0,
400,
600,
800,
1,000
and
1,200
mg/
L
at
natural
pH.
In
a
separate
study,
the
same
concentrations
(
except
1,200
mg/
L)
were
tested
and
the
pH
was
adjusted
to
7.5
±
0.5
using
sodium
hydroxide.
The
LC
50
was
1,020
mg/
L
at
natural
pH;
there
were
no
deaths
at
800
mg/
L
and
10/
10
deaths
at
1,200
mg/
L.
At
pH
of
7.5
±
0.5,
there
were
no
deaths
at
1,000
mg/
L
(
Schlienger
and
Groner
as
cited
in
SIDS
2003).
Page
15
of
16
Drinking
Water
Considerations:

There
are
no
federal
drinking
water
standards
for
ascorbic
acid
or
ascorbyl
palmitate.

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
ascorbic
acid
and
ascorbyl
palmitate
assessed
in
this
document
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
ascorbic
acid
and
ascorbyl
palmitate
and
any
other
substances
and
ascorbic
acid
and
ascorbyl
palmitate
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
ascorbic
acid
and
ascorbyl
palmitate
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.
These
numbers
were
not
available
at
the
time
of
document
signature.
No
other
changes
were
made
to
the
document.)

Cosmetic
Ingredient
Review
(
CIR).
1997.
Final
Report
of
the
Safety
Assessment
of
Ascorbyl
palmitate,
ascorbyl
dipalmitate,
ascorbyl
stearate,
erythorbic
acid
and
sodium
erythorbate.
Washington
DC.
April.
(
Also
published
in
the
International
Journal
of
Toxicology,
Vol
18(
3),
1999).

FAO/
WHO
1974.
Seventeenth
Report
of
the
Joint
FAO/
WHO
Expert
Committee
on
Food
Additives.
Ascorbyl
Palmitate
and
Stearate.
World
Health
Organization
Technical
Report
Ser.
No.
539;
FAO
Nutrition
meetings
Report
Series
No.
53.

Food
and
Drug
Administration
(
FDA).
1979.
Evaluation
of
the
Health
Aspects
of
Ascorbic
Acid,
Sodium
Ascorbate,
Calcium
Ascorbate,
Erythorbic
Acid,
Sodium
Erythorbate,
and
Ascorbyl
Palmitate
as
Food
Ingredients.
Bureau
of
Foods,
FDA,
Department
of
Health,
Education
and
Welfare.
Washington,
D.
C.
Prepared
by
Life
Sciences
Research
Office,
Page
16
of
16
Federation
of
American
Societies
for
Experimental
Biology.
Bethesda
MD.
(
MRID
No.
46069101)

SIDS
Data
Set
on
L­
Ascorbic
Acid
(
Vitamin
C).
2003.
http://
irptc.
unep.
ch/
irptc/
sids/
volume4/
part1/
ascorbic/
sidsdata.
html.

TOXNET
2003.
Hazardous
Substances
Databank
(
HSDB).
On­
line
Scientific
Search
Engine,
National
Library
of
Medicine,
National
Institute
of
Health.
Http://
www.
toxnet.
nlm.
nih.
gov.
Search
term:
Ascorbyl
Palmitate
U.
S.
Environmental
Protection
Agency
(
EPA).
Structure
Activity
Relationship
(
SAR).
1995.
Structure
Activity
Team
Report.
OPPT.
Ascorbyl
palmitate.

U.
S.
Environmental
Protection
Agency
(
EPA).
2002.
"
Tolerance
Review
of
Compounds
Known
as
Fatty
Acids,
Fatty
Acid
Salts,
and
Fatty
Acid
Esters,
and
Fatty
Acid
Derivatives
Classified
as
Inert
Ingredients
in
Terrestrial
and/
or
Aquatic
Agricultural
and
Non­
Agricultural
Uses".
Memorandum
from
S.
C.
Terms/
H.
Craven,
Environmental
Fate
and
Effects
Division
(
EFED)
to
M.
Perry,
Special
Review
and
Reregistration
Division
(
SRRD).
May
15,
2002.