Page
1
of
12
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
February
17,
2004
MEMORANDUM
SUBJECT:
Tolerance
Reassessment
Decisions
Completed
by
the
Lower
Toxicity
Pesticide
Chemical
Focus
Group
FROM:
Betty
Shackleford,
Associate
Director
Registration
Division
TO:
Peter
Caulkins,
Associate
Director
Special
Review
and
Reregistration
Division
Please
find
attached
the
Focus
Group
Decision
Document
for
vanillin.
The
tolerance
exemption
for
vanillin
in
40
CFR
180.1001(
d)
is
reassessed.
The
List
classification
of
vanillin
is
confirmed
as
List
4A.

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

Attachment
(
1)
Page
2
of
12
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
February
17,
2004
MEMORANDUM
FROM:
Kathryn
Boyle,
Chair
Lower
Toxicity
Pesticide
Chemical
Focus
Group
Registration
Division
TO:
Betty
Shackleford,
Associate
Director
Registration
Division
SUBJECT:
Recommendation
for
Tolerance
Reassessment
The
attached
science
assessment
reviews
the
available
information
on
vanillin.
Vanillin
assessments
were
previously
performed
by
the
World
Health
Organization
(
WHO)
in
1967
and
the
1996
SIDS
(
Screening
Information
Data
Set)
Report
issued
by
the
Organization
for
Economic
Cooperation
and
Development
(
OECD).
Neither
of
these
assessments
directly
addressed
the
use
of
vanillin
as
an
inert
ingredient
in
pesticide
products.
However,
the
amount
of
information
on
vanillin
is
extensive.

Vanillin
(
or
vanilla)
has
been
widely­
used
for
many
years
as
evidenced
by
a
metabolism
study
that
was
reported
in
1880.
It
is
used
as
a
flavoring
in
foods
and
beverages,
and
as
a
fragrance
in
cosmetics,
personal­
care
products,
and
perfumes.
Vanillin
is
GRAS
(
generally
recognized
as
safe)
under
21
CFR
182.90
and
21
CFR
182.60.

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
vanillin
when
used
as
an
inert
ingredient
in
pesticide
products.
The
tolerance
exemption
in
40
CFR
180.1001(
d)
is
reassessed.
The
classification
as
List
4A
is
confirmed.
Page
3
of
12
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
January
29,
2004
Memorandum
Subject:
Vanillin:
Science
Assessment
Document
for
Tolerance
Reassessment.

CAS
No.:
121­
33­
5
Chemical
Class:
substituted
benzaldehyde
40
CFR:
180.1001
(
d)

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

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

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

Background:

Attached
is
the
Lower
Risk
Pesticide
Chemical
Focus
Group's
science
assessment
for
vanillin.
This
assessment
summarizes
available
information
on
the
uses,
physical/
chemical
properties,
toxicological
effects,
exposure
profile,
and
environmental
fate
and
ecotoxicity
for
this
inert
ingredient
substance.
In
performing
this
assessment,
EPA
has
relied
on
a
peer­
reviewed
evaluation
performed
by
a
committee
of
the
Food
and
Agriculture
Organization
of
the
World
Health
Organization
(
WHO)
and
an
Organization
for
Economic
Cooperation
and
Development
(
OECD)
Screening
Information
Data
Set
(
SIDS)
assessment,
as
well
as
TOXNET
data
and
the
results
of
ECOSAR
modeling
for
the
environmental
fate
and
effects
aspects
of
the
assessment.
Page
4
of
12
I.
Executive
Summary:

Vanillin
is
a
substituted
benzaldehyde.
It
has
been
classified
by
the
U.
S.
Food
and
Drug
Administration
as
Generally
Recognized
As
Safe
(
GRAS)
for
its
use
as
a
substance
migrating
to
food
from
paper
and
paperboard
products
used
in
food
packaging,
as
well
as
when
used
as
a
synthetic
flavoring
substance
and
adjuvant.
An
OECD
SIDS
assessment
(
1996)
concluded
that
"
almost
every
human
globally
is
exposed
to
minute
amounts
of
vanillin
by
ingestion."

Open
literature
studies
and
information
from
various
assessments
show
that
there
are
a
number
of
toxicological
studies
with
vanillin,
and
these
data
indicate
that
vanillin
does
not
pose
any
serious
health
effects.
Vanillin
is
rapidly
metabolized,
with
its
conjugated
products
readily
excreted
in
the
urine.

A
WHO
Joint
Expert
Committee
on
Food
Additives
Committee
summary
report
(
1967)
concluded
that
for
vanillin,
"
the
metabolic
fate
of
this
flavouring
is
well
established
in
man
and
animals,"
and
that
the
"
estimate
of
acceptable
daily
intake
for
man
is
10
mg/
kg
body­
weight."

Vanillin
is
soluble
in
water,
and
will
remain
in
solution,
since
it
is
not
likely
to
sorb
to
particulate
matter
or
sediments.
Vanillin
is
not
likely
to
volatilize
from
water
or
from
moist
or
dry
soils.
It
has
been
found
to
be
biodegraded
in
both
aerobic
and
anaerobic
conditions,
and
vanillin
has
been
found
to
be
relatively
non­
toxic
to
aquatic
plant
and
animal
species.

Based
on
available
information
on
vanillin,
its
expected
use
patterns,
with
its
GRAS
status
and
safe,
long­
term
history
of
use
in
food
packaging
and
as
synthetic
flavoring
substance
and
adjuvant,
its
use
in
commercially­
available,
over­
the­
counter
foods,
and
its
use
as
a
fragrance
in
perfumes,
as
well
as
its
rapid
metabolism
and
low
degree
of
observed
toxicity
in
humans
and
animals,
the
Lower
Risk
Pesticide
Chemical
Focus
Group
has
determined
that
a
screening
level
quantitative
risk
assessment
is
not
required
for
vanillin.

II.
Use
Information:

The
pesticidal
and
non­
pesticidal
uses
of
vanillin
are
summarized
briefly
below.

Table
1.
Use
Pattern
(
pesticidal
inert
ingredient)

Chemical
Name
PC
Code
40
CFR
Use
Pattern
(
Pesticidal)
Current
Inert
List
vanillin
800738
180.1001
(
d)
Attractant
4A
Vanillin
also
has
an
active
ingredient
PC
Code,
115801,
but
there
are
no
current
end­
use
products
registered
at
this
time.
Page
5
of
12
Use
Pattern
(
non­
pesticidal):

Vanillin
is
generally
recognized
as
safe
(
GRAS)
by
the
U.
S.
FDA
when
used
as
a
substance
migrating
to
food
from
paper
and
paperboard
products
used
in
food
packaging
(
21
CFR
182.90),
as
well
as
GRAS
when
used
as
a
synthetic
flavoring
substance
and
adjuvant
(
21
CFR
182.60).
Vanillin
has
the
following
uses:
as
an
additive
(
flavoring
agent)
for
food
and
beverages,
as
a
fragrance
(
in
perfumes),
and
for
intermediates
for
pharmaceuticals.
According
to
the
OECD
SIDS
assessment
(
1996),
"
Minor
amounts
[
of
vanillin]
are
applied
as
skin
care
products,
perfumes
etc.
The
global
use
of
vanillin
in
food
and
beverages
imply
[
sic]
that
almost
every
human
globally
is
exposed
to
minute
amounts
of
vanillin
by
ingestion."

Vanillin
is
also
known
as
vanillic
aldehyde
and
vanilla.
It
is
a
substituted
benzaldehyde,
and
its
recognized
chemical
name
is
4­
hydroxy­
3­
methoxy­
benzaldehyde.
Vanillin
is
produced
naturally
in
vanilla
beans;
and
synthetically
primarily
from
the
waste
(
lignin)
from
the
wood
pulp
industry,
and
also
from
eugenol
or
guaiacol,
as
well
as
from
safrole.
Vanillin
is
mainly
utilized
as
an
additive
to
food
and
beverages
(
more
than
60%),
but
considerable
amounts
are
used
for
fragrances
in
perfumes
(
20­
25%),
while
5­
10%
is
used
for
intermediates
in
pharmaceuticals.

Figure
1.
Chemical
Structure
of
Vanillin
(
Source:
ChemIDPlus;
http://
toxnet.
nlm.
nih.
gov/)

Table
2.
Physical/
Chemical
Properties
of
Vanillin
(
from
OECD
SIDS
assessment
(
1996))

Molecular
formula
C8H8O3
Molecular
weight
152.15
Melting
point
80­
81
°
C
Solubility
in
water
11,000
mg/
L
at
30
°
C
pH
4.3
(
5%
aqueous
solution
[
saturated
solution])

Density/
Specific
Gravity
1.056
g/
mL
@
19
°
C
/
4
°
C
Vapor
Density
5.2
Estimated
Octanol/
Water
Partition
Coefficient
log
Kow
=
1.23
­
1.37
Physical
state
white
or
slightly
yellow
needles
Page
6
of
12
Dissociation
Constant
pKa
=
7.38
@
25
°
C
Vapor
Pressure
1.2
x
10­
4
mm
Hg
@
25
°
C;
0.33
Pa
Estimated
Henry's
Law
constant
2.1
x
10­
9
atm­
m3/
mole
Estimated
Soil
Sorption
Coefficient
Koc
=
130
Bioconcentration
Factor
6.0
UV
Absorption
Spectrum
absorbs
light
at
wavelengths
of
308
and
278
nm
IV.
Hazard
Assessment:

Toxicological
Profile:

Table
3.
Summary
of
Acute
Toxicity
Data
on
Vanillin.

Test
Species
Results
Oral
LD50
rat
1580
mg/
kg
­
4200
mg/
kg
(
7
different
studies)

guinea
pig
1400
mg/
kg
rabbit
3000
mg/
kg
Dermal
LD50
rat
>
2000
mg/
kg
rabbit
>
5010
mg/
kg
Eye
Irritation
rabbit
slightly
irritating,
improving
from
48­
120
hrs,
and
no
effects
seen
at
168
hrs
Dermal
Irritation
rabbit
no
irritation
guinea
pig
no
signs
of
irritation
Dermal
Sensitization
guinea
pig
Buehler
Closed
patch
repeat
exposure
test:
no
signs
of
sensitization
or
allergy
guinea
pig
Maximization
test:
Freunds
complete
adjuvance:
positive
allergic
response
guinea
pig
Freunds
complete
adjuvance
with
10%
acetone:
weak
sensitizer
mouse
Mouse
ear
swelling
test:
50%
vanillin
in
ethanol:
no
sensitization
Vanillin
is
moderately
toxic
in
acute
oral
toxicity
studies,
but
essentially
non­
toxic
in
the
acute
dermal
toxicity
study
in
the
rat
(
Table
3).
While
vanillin
is
slightly
irritating
to
the
eye,
it
is
non­
irritating
in
dermal
exposure
tests.
Dermal
sensitization
studies
have
shown
both
allergic
and
weak
sensitizing
results
with
vanillin,
as
well
as
results
which
were
negative.

The
OECD
SIDS
assessment
(
1996)
reported
results
from
dermal
exposures
with
human
volunteers.
In
primary
irritation
studies
and
in
patch
tests,
no
signs
of
irritation
or
sensitization
Page
7
of
12
were
observed.
In
maximization
tests,
human
volunteers
were
exposed
first
to
sodium
lauryl
sulfate,
then
to
repeated
48
hour
exposures
to
vanillin
(
at
2­
5%
in
petrolatum),
and
vanillin
was
negative,
so
it
was
"
concluded
to
be
non­
sensitizing
in
humans."
However,
in
humans
already
sensitized
to
balsam
of
Peru,
positive
reactions
were
exhibited
to
vanillin,
so
the
OECD
SIDS
assessment
(
1996)
concluded
that
vanillin
was
"
considered
to
be
a
secondary
allergen."

There
are
no
concerns
for
mutagenicity
for
vanillin.
The
mutagenicity
studies
cited
in
the
OECD
SIDS
assessment
(
1996)
include
both
in
vivo
and
in
vitro
assays.
All
of
the
in
vivo
assays
produced
negative
results
for
genetic
toxicity
as
did
the
majority
of
the
in
vitro
assays.
Additionally,
a
two
year
oral
feeding
study
in
rats
was
negative
for
carcinogenicity,
as
well
as
any
toxic
effects,
and
repeated
dose
studies
where
reproductive
parameters
were
measured
also
produced
negative
results.

The
World
Health
Organization
(
WHO)
Joint
Expert
Committee
on
Food
Additives
(
JECFA)
summary
report
(
1967)
reported
that
vanillin
is
converted
to
vanillic
acid,
mainly
excreted
(
in
the
urine)
as
free
acid
or
the
conjugated
ethereal
sulfate
or
glucurovanillic
acid.
Its
metabolism
is
by
the
following
pathway:
vanillin
first
undergoes
rapid
conjugation,
then
slow
oxidation
to
conjugated
vanillic
acid,
some
of
which
then
becomes
demethylated
to
conjugated
protocatechuic
acid,
which
is
then
further
decarboxylated
to
conjugated
catechol,
with
further
complete
oxidation
then
occurring
by
the
opening
of
the
aromatic
ring
between
the
C
3
and
C
4
carbons.
In
another
study
in
the
rabbit,
conjugated
vanillic
acid
and
conjugated
protocatechuic
acid
were
in
equilibrium
with
the
corresponding
free
acids,
with
all
appearing
in
the
urine,
but
there
being
no
free
vanillin
excreted
in
the
urine.

The
JECFA
summary
report
(
WHO
1967)
also
described
results
from
four
short­
term
oral
or
feeding
studies
in
the
rat,
and
in
general,
no
deleterious
effects
were
reported.
In
addition,
results
were
reported
from
a
long­
term
study
in
which
groups
of
rats
were
fed
0,
0.5,
1.0,
or
2.0%
(
0,
5000,
10,000,
or
20,000
ppm,
respectively)
vanillin
in
their
diets
for
2
years
without
any
deleterious
effects
being
observed.
On
the
basis
of
these
studies,
the
JECFA
summary
report
(
WHO
1967)
concluded
the
following:

"
The
metabolic
fate
of
this
flavouring
is
well
established
in
man
and
animals.
The
shortterm
studies
give
conflicting
results,
but
the
long­
term
study
is
used
for
evaluation.
Evaluation:
Level
causing
no
toxicological
effect:
Rat.
2
per
cent
(=
20,000
ppm)
in
the
diet,
equivalent
to
1000
mg/
kg
body­
weight/
day.
Estimate
of
acceptable
daily
intake
for
man:
Unconditional
acceptance:
0­
10
mg/
kg
body­
weight."

In
the
more
recent
OECD
SIDS
assessment
(
1996),
various
other
repeated­
dose
oral
toxicity
studies
were
also
reviewed,
with
only
no
adverse
effects
levels
(
NOAELs)
having
been
reported
in
most
studies,
except
for
one,
unpublished
study.
On
the
basis
of
these
various
studies,
the
OECD
SIDS
assessment
(
1996)
utilized
an
NOAEL
of
50,000
ppm
(
2500
mg/
kg/
day)
from
the
1
year
study.

Table
4.
Results
of
Repeated­
Dose
Feeding
Studies
Reported
in
OECD
SIDS
assessment
(
1996)
Page
8
of
12
Species
Duration
Dosing
Levels
Results
Reported
rat
27
weeks
1000
ppm
(
50
mg/
kg/
day)
no
adverse
effects
were
observed
rat
16
weeks
10,000
ppm
(
500
mg/
kg/
day)
no
adverse
effects
were
observed
male
rats
1
year
20,000
or
50,000
ppm
(
1000
or
2500
mg/
kg/
day,
respectively)
no
adverse
effects
were
observed
male
rats
26
weeks
1000,
5000
or
10,000
ppm
(
50,
250,
or
500
mg/
kg/
day,
respectively)
no
adverse
effects
were
observed
rats
91
days
3000,
10,000,
or
50,000
ppm
(
150,
500,
or
2500
mg/
kg/
day)
NOAEL:
3,000
ppm
(
150
mg/
kg/
day);
LOAEL:
10,000
ppm
(
500
mg/
kg/
day).
1
dogs
26­
27
weeks
0,
25,
or
100
mg/
kg/
day
in
caps
no
particular
toxicity
was
observed
1
Included
in
this
table
because
the
data
were
cited
in
the
OECD
SIDS
assessment
(
1996);
however,
that
assessment
stated
that
"
this
study
is
unpublished,
but
the
information
has
been
taken
from
a
citation
in
1963.
The
design
and
the
details
of
the
study
are
unknown,
thus,
the
other
studies
seem
more
reliable."

Special
Considerations
for
Infants
and
Children:
At
this
time,
there
is
no
concern
for
vanillin
to
have
potential
sensitivity
to
infants
and
children.
Although
no
developmental
or
reproductive
studies
were
identified,
the
Agency
does
not
believe
there
are
concerns
for
adverse
effects
in
infants
or
children,
given
the
widespread
historical
use
of
vanillin
in
food
products
to
which
pregnant
women
and
children
have
been
exposed
without
adverse
effects.
Thus,
a
safety
factor
analysis
has
not
been
used
to
assess
the
risk.
For
the
same
reasons,
the
additional
tenfold
safety
factor
is
unnecessary,
and
has
been
removed.

V.
Exposure
Assessment:

Exposure
to
vanillin
may
occur
through
its
FDA­
approved
GRAS
uses
in
food
packaging
and
as
a
food
additive,
when
used
as
a
synthetic
flavoring
substance
and
adjuvant,
as
well
as
its
use
as
a
fragrance
in
cosmetics.
Vanillin
has
been
used
as
a
food
additive
for
many
years;
in
fact,
one
of
the
first
scientific
studies
on
vanillin
was
concerning
its
metabolism,
having
been
reported
in
the
19th
century,
in
1880
(
Preusse,
1880,
as
cited
in
the
OECD
SIDS
assessment
(
1996)).
In
addition,
the
production
volume
of
vanillin
is
sufficiently
high
that
the
Agency
considers
it
to
be
a
High
Production
Volume
(
HPV)
chemical.
Based
on
the
extensive
and
long­
standing
use
of
vanillin
in
many
types
of
foods
(
approved
FDA
uses),
the
potential
exposures
to
the
substance
as
a
result
of
use
in
pesticide
products
are
expected
to
be
minimal.
Therefore,
a
screening
level
quantitative
exposure
assessment
has
not
been
conducted.

VI.
Risk
Characterization:
Page
9
of
12
Taking
into
consideration
all
available
information
on
vanillin,
including
its
designations
by
FDA
as
GRAS,
the
information
compiled
in
a
WHO
summary
report,
and
an
OECD
SIDS
assessment,
as
well
as
its
long­
term
use
as
a
flavoring
agent
in
foods
and
as
a
fragrance
in
perfumes,
it
is
concluded
that
the
use
of
vanillin
as
an
inert
ingredient
in
pesticide
products
is
unlikely
to
pose
a
significant
hazard
to
the
general
public
or
any
population
subgroup.
Vanillin
is
readily
metabolized,
and
in
long­
term
feeding
studies,
it
showed
no
adverse
effects
and
produced
no
evidence
of
carcinogenic
potential,
with
no
toxicological
effects
observed
in
the
rat
at
20,000
ppm
(
2%)
in
the
diet
(
equivalent
to
1000
mg/
kg
bw/
day),
so
the
WHO
summary
report
estimate
of
the
acceptable
daily
intake
in
humans
was
10
mg/
kg
bw.
As
a
result,
OPP
is
recommending
a
qualitative
approach
to
assessing
human
health
risks
from
exposure
to
vanillin.

VII.
Environmental
Fate/
Ecotoxicity/
Drinking
Water
Considerations:

HSDB
in
TOXNET
discusses
the
environmental
fate
of
vanillin.
This
information
from
HSDB
has
been
supplemented
with
predictive
modeling,
based
on
structure
activity
relationships
(
Meylan
and
Howard,
1998).

Based
on
its
moderate
K
oc
(
130
L/
g)
and
low
K
ow
(
1.37)
values,
vanillin
is
classified
as
highly
mobile
in
soil
(
McCall
et
al.
[
undated]).
It
has
the
potential
to
slowly
volatilize
from
dry
soil
surfaces,
based
on
its
vapor
pressure
of
about
1.2
x
10­
4
mm
Hg.
Vanillin
has
been
observed
to
be
completely
degraded
from
pasture
soil
in
12.5
days,
but
with
an
initial
lag
period
of
4
days.
Overall
half­
lives
in
acclimated
systems
would
range
from
days
for
primary
degradation
to
weeks
for
ultimate
degradation
(
mineralization),
based
on
the
ready
biodegradability
model
(
Meylan
and
Howard,
2000).
Due
to
the
lack
of
hydrolyzable
functional
groups,
abiotic
degradation
of
vanillin
in
the
soil
would
not
be
expected
to
be
an
important
fate
process.

Vanillin
is
very
soluble
in
water
(
11,000
mg/
L).
Based
on
its
K
oc
and
K
ow
values,
vanillin
would
not
be
expected
to
adsorb
to
suspended
solids
or
sediments
in
water.
Volatilization
from
water
would
not
be
expected
to
be
an
major
fate
process
for
vanillin,
based
on
its
Henry's
Law
constant
(
2.1
x
10­
9
atm­
m3).
The
dissociation
constant
for
vanillin
(
pKa:
7.4)
suggests
that
in
waters
in
the
range
of
environmentally
relevant
pHs,
it
would
exist
partly
in
an
ionized
form.
Based
on
its
low
K
ow
and
low
estimated
Bioconcentration
Factor
(
6),
there
is
a
low
potential
for
bioconcentration
in
aquatic
animals.
The
rapid
biodegradation
of
vanillin
in
soil
under
aerobic
conditions
suggests
that
aerobic
biodegradation
in
water
would
be
an
important
fate
process.
Under
anaerobic
test
conditions,
vanillin
was
72%
degraded
in
42
days,
with
a
lag
time
of
12
days,
in
a
closed
bottle
serum
test
using
settled
domestic
sewage
seed.
Vanillin
is
not
expected
to
undergo
hydrolysis
in
the
environment
due
to
the
lack
of
hydrolyzable
functional
groups.

If
any
vanillin
should
enter
the
atmospheric
compartment
of
the
environment,
its
vapor
pressure
being
1.2
x
10­
4
mm
Hg,
it
is
expected
to
exist
solely
as
a
vapor.
Vapor­
phase
vanillin
would
be
degraded
in
the
atmosphere
by
reactions
with
photochemically­
produced
hydroxyl
radicals,
with
estimated
half­
life
values
on
the
order
of
14
hours.
Vanillin
also
has
a
potential
to
photolyze
directly,
but
the
kinetics
of
the
potential
photolysis
are
unknown.
Page
10
of
12
Vanillin
is
relatively
non­
toxic
in
tests
with
various
aquatic
species,
based
on
the
data
in
the
OECD
SIDS
assessment
(
1996)
(
Table
5).
The
LC
50
values
to
the
fathead
minnows
indicate
that
vanillin
is
relatively
non­
toxic
in
short­
term
acute
tests,
but
there
were
no
data
available
for
chronic
toxicity
to
fish.
Results
were
reported
for
longer­
term
exposures
with
Daphnia;
after
13
days
exposure
to
100
mg/
L,
all
the
Daphnia
became
immobilized,
with
the
immobilization
EC
50
for
the
period
from
13
to
21
days
estimated
to
be
75
mg/
L.

Table
5.
Summary
of
Ecotoxicity
Data
(
Source:
OECD
SIDS
assessment
(
1996))

Organism
(
Species
name)
Toxicity
data
(
LC50,
unless
indicated)
at
respective
time
period:

Fathead
minnow
(
Pimephales
promelas)
1
hr:
173
­
370
mg/
L
24
hr:
100
­
131
mg/
L
48
hr:
68.3
­
123
mg/
L
72
hr:
57
­
123
mg/
L
96
hr:
57
­
123
mg/
L
Water
flea
(
Daphnia
sp.)
24
hr
EC50:
180
mg/
L
21
day
reproduction
study:
EC50
for
reproduction:
16
mg/
L
measured
(
24
mg/
L
nominal)
NOEC
for
reproduction:
5.9
mg/
L
measured
(
10
mg/
L
nominal)
LOEC
for
reproduction:
10
mg/
L
measured
(
18
mg/
L
nominal)

Green
algae
(
Scenedesmus
obliquus)
(
Chlorella
variegata)
only
1
test
concentration,
2
mg/
L:
reduced
growth
after
3
days,
but
no
effect
was
observed
after
7,
14,
and
21
days
exposure
(
identical
results
reported
for
both
species
of
green
algae).

Diatoms
(
Gomphonema
parvulum)

(
Nitzschia
palea)
with
both
species,
only
1
test
concentration,
2
mg/
L:
No
growth
after
3
days,
and
reduced
growth
after
7,
14,
and
21
days.

Unaffected
at
3
days,
reduced
growth
at
7
days,
and
growth
was
normalized
again
after
14
and
21
days.

Blue­
green
algae
(
Cylinderospermum
licheneniforme)
(
Mycrocystis
aeruginosa)
only
1
test
concentration,
2
mg/
L:
"
no
effect
was
seen"
after
3,
7,
14,
and
21
days
exposure
(
identical
results
reported
for
both
species
of
blue­
green
algae).

Green
algae
(
Chlorella
vulgaris)
after
80
hr
exposure
to
152
mg/
L,
50%
growth
reduction;
after
160
hr
exposure
to
152
mg/
L,
growth
inhibition
was
30%;
no
effects
were
observed
at
15
mg/
L
or
1.5
mg/
L.

earthworm
(
Eisenia
foetida)
soil
concentrations
of
0,
0.1,
1,
4,
and
8%
for
42
day
exposure
period:
4%
was
lowest
concentration
which
significantly
reduced
growth
rate,
and
cause
death
of
80%
of
worms;
thus,
NOEC
value
reported
to
be
10
g/
kg
soil
dry
weight
(=
1%),
and
LOEC
was
40
g/
mg
soil
dry
weight
(=
4%),
at
which
concentration,
the
mortality
of
worms
was
80%.

VIII.
Cumulative
Exposure:
Page
11
of
12
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
vanillin
has
a
common
mechanism
of
toxicity
with
other
substances.
Unlike
other
pesticide
substances
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
vanillin
and
any
other
substances,
and
vanillin
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
vanillin
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

References:

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

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

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

Organization
for
Economic
Cooperation
and
Development
(
OECD)
Screening
Information
Data
Sets
(
SIDS)
for
High
Production
Volume
Chemicals.
Processed
by
United
Nations
Environment
Programme
(
UNEP)
Chemicals
as
a
contribution
to
the
Inter­
Organization
Programme
for
the
Sound
Management
for
Chemicals
(
IOMC).
Volume
5,
Part
2.
Introduction.
4
pp.
Available
at
http://
www.
inchem.
org/
documents/
sids/
sids/
sids5b01.
htm.
(
MRID
No.
461082­
01).
VANILLIN.
SIDS
INITIAL
ASSESSMENT
PROFILE.
Dated
20.08.96
[
August
20,
1996].
OECD
Screening
Information
Data
Sets
(
SIDS).
117
pp.
Available
at
http://
www.
inchem.
org/
documents/
sids/
sids/
sids5b06.
htm.
(
MRID
No.
461082­
02).

TOXNET.
Department
of
Health
and
Human
Services,
National
Institutes
of
Health,
U.
S.
Page
12
of
12
National
Library
of
Medicine,
Specialized
Information
Services.
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Hazardous
Substances
Data
Bank
(
HSDB)
and
Chemical
Carcinogenesis
Research
Information
System
(
CCRIS)
and
Genetic
Toxicology
(
Mutagenicity)
(
GENE­
TOX).
Vanillin
(
CAS
Registry
Number
121­
33­
5).
Available
at
http://
www.
toxnet.
nlm.
nih.
gov.

World
Health
Organization
(
WHO).
1967.
Toxicological
Evaluation
of
Some
Flavouring
Substances
and
Non­
Nutritive
Sweetening
Agents.
125.
Vanillin.
International
Programme
on
Chemical
Safety,
Food
and
Agriculture
Organization
Nutrition
Meetings
Report
Series
No.
44A.
4
pp.
Available
at
http://
www.
inchem.
org/
documents/
jecfa/
jecmono/
v44aje34.
htm.
(
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461081­
01).
