Document ID: EPA-HQ-OPP-2004-0335-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-10-18T04:00Z

Exposure
and
Risk
Assessment
on
Lower
Risk
Pesticide
Chemicals
D­
Limonene
Prepared
by
Special
Review
and
Reregistration
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
1801
South
Bell
Street
Arlington,
VA
22202
1
Background:

This
document
represents
the
Lower
Risk
Pesticide
Chemical
Focus
Group's
(
LRPCFG)
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
on
d­
limonene.
This
assessment
summarizes
the
available
information
on
the
use,
physical/
chemical
properties,
toxicological
effects,
exposure
profiles,
and
environmental
fate
and
ecotoxicity
for
d­
limonene.
In
performing
this
assessment,
EPA
has
utilized
reviews
previously
performed
by
EPA
and
the
World
Health
Organization
(
WHO).
The
Agency
did
not
review
any
data
in
association
with
this
assessment.

In
September
1994,
a
Registration
Eligibility
Decision
(
RED)
document
was
issued
for
d­
limonene
and
a
tolerance
exemption
has
also
been
granted
for
its
use
as
an
inert
ingredient
as
a
solvent
or
a
fragrance
in
pesticide
formulations.
The
purpose
of
this
TRED
document
is
to
reassess
the
exemptions
from
the
requirement
of
a
tolerance
for
residues
of
this
chemical
when
used
as
an
active
ingredient
and
an
inert
ingredient
in
pesticide
formulations.
Because
the
original
d­
limonene
RED
was
issued
in
September
1994,
prior
to
the
development
of
the
Food
Quality
Protection
Act
(
FQPA)
in
August
1996,
tolerances
also
need
to
be
reassessed
to
meet
the
FQPA
standard.
The
Agency
has
considered
any
new
data
generated
after
the
tolerance
exemption
was
issued,
new
Agency
guidance
or
other
federal
regulations,
as
well
as
previously
available
information
in
this
assessment.
The
Agency
was
assisted
in
the
preparation
of
parts
of
this
document
by
its
contractor
Versar.

I.
Executive
Summary:

d­
Limonene
has
a
lemon­
like
flavor
and
smell,
and
occurs
naturally
in
citrus
and
certain
fruits,
vegetables,
meats
and
spices.
d­
Limonene
is
used
as
both
an
active
and
inert
ingredient
in
pesticide
products,
and
as
an
ingredient
in
food
products,
soaps,
and
perfumes.
As
an
active
ingredient,
it
is
used
as
an
insecticide,
insect
repellent,
and
animal
(
dog
and
cat)
repellent.
As
a
pesticide
inert
ingredient
is
used
as
a
solvent
or
fragrance.
It
is
also
found
in
consumer
products
such
as
certain
foods,
soaps,
and
perfumes.
FDA
considers
d­
limonene
to
be
GRAS
as
a
food
additive
when
used
as
a
synthetic
flavoring
substance
and
adjuvant
(
21CFR
182.60).
d­
Limonene
is
not
registered
for
food
or
feed
crop
uses
as
an
active
ingredient,
but
can
be
used
on
compost
and
manure.

In
conducting
risk
assessments,
an
oral
LOAEL
of
400
mg/
kg­
bw/
day
was
used
for
the
short­
term
exposure
scenarios,
while
an
oral
NOAEL
of
150
mg/
kg­
bw/
day
was
used
for
the
long­
term
exposure
scenarios.
Since
the
short­
term
toxicity
endpoint
is
based
on
an
LOAEL,
an
additional
safety
factor
of
3X
was
applied
to
the
Margin
of
Exposure
(
MOE)
of
100.
Thus,
an
MOE
of
300
is
of
concern
for
the
shortterm
exposure
scenarios.
For
long­
term
exposures,
an
additional
safety
factor
was
not
necessary,
so
the
MOE
of
concern
is
100.

For
products
containing
d­
limonene
as
an
active
ingredient,
exposure
scenarios
were
chosen
based
on
the
anticipated
use
patterns
and
current
labeling
for
d­
limonene
pesticide
products.
Application
rates
were
also
estimated
based
on
information
provided
on
the
product
labels.
Calculated
MOEs
ranged
from
a
low
of
81
for
the
application
of
pet
dips
to
a
high
of
7,300
for
the
application
of
liquid
pesticides
with
a
watering
can.
For
products
containing
d­
limonene
as
an
inert
ingredient,
the
Pesticide
Inert
Risk
Assessment
Tool
(
PIRAT,
test
version)
was
used
to
estimate
handler
dermal
and
inhalation
exposure.
It
was
assumed
that
exposure
would
be
to
pressurized
liquid,
ready­
to­
use
liquid,
and
emulsifiable
and
soluble
concentrate
formulations,
all
of
which
may
contain
inert
ingredients
used
as
fragrances.
Calculated
MOEs
ranged
from
a
low
of
420
for
ready­
to­
use
outdoor
paints/
stains
that
are
applied
by
airless
sprayer
to
a
high
of
2
3,300,000
for
emulsifiable
concentrates
applied
using
a
backpack
sprayer.
To
examine
exposure
to
dlimonene
through
the
use
of
products
such
as
general
purpose
cleaners
and
aerosol
spray
cans,
the
Consumer
Exposure
Module
(
CEM)
was
used.

In
this
assessment,
the
only
exposure
scenario
that
exceeded
the
Agency's
level
of
concern
was
the
use
of
pet
dips
with
d­
limonene
as
an
active
ingredient
(
MOE
of
81).
However,
several
factors
need
to
be
considered
when
interpreting
this
MOE,
including:
(
1)
the
uncertainties
associated
with
the
assessment
as
outlined
in
the
OPP
Health
Effects
Division's
Standard
Operating
Procedures
(
SOP)
for
Residential
Exposure
Assessments,
(
2)
a
multi­
day
continuously
dosing
endpoint
was
compared
to
a
pet
dip
scenario
for
which
the
Agency
believes
that
it
is
most
likely
that
there
will
only
be
a
single
event
exposure
for
less
than
an
hour's
duration,
(
3)
the
dermal
absorption
rate
for
this
assessment
is
assumed
to
be
100%
of
the
oral
,
which
may
be
conservative
for
this
particular
chemical,
and
(
4)
on
the
label
in
question,
there
is
a
specific
recommendation
that
users
wear
rubber
gloves
while
performing
the
pet
dip
activity.
The
Agency
does
not
require
personal
protective
equipment
for
residential
use
labels,
but
the
Agency
also
does
not
typically
request
that
registrants
remove
PPE
from
their
existing
labels,
when
the
use
of
such
PPE
is
health
protective
for
users.
Taken
together,
these
factors
make
a
strong
case
that
the
resulting
estimate
significantly
overestimate
exposures
and
risks
for
this
pet
dip
scenario.

For
chronic
dietary
assessments,
a
NOAEL
of
150
mg/
kg­
bw/
d
was
selected,
based
on
an
103­
week
oral
gavage
study
in
the
male
rat.
For
all
populations
addressed,
the
MOEs
for
d­
limonene
were
greater
than
the
MOE
of
concern
of
100.

In
terms
of
environmental
exposures,
studies
have
been
performed
on
both
the
technical
form
of
d­
limonene
and
the
formulated
products
and
have
been
shown
to
be
practically
nontoxic
or
slightly
toxic
to
birds,
fish
and
invertebrates.

II.
Use
Information:

d­
Limonene
occurs
naturally
in
citrus
and
certain
fruits,
vegetables,
meats
and
spices.
It
has
a
lemon­
like
flavor
and
smell,
and
is
used
as
both
an
active
and
inert
ingredient
in
various
products.
As
an
active
ingredient,
it
is
used
as
an
insecticide,
insect
repellent,
and
animal
(
dog
and
cat)
repellent.
As
a
pesticide
inert
ingredient
is
used
as
a
solvent
or
fragrance.
It
is
also
found
in
consumer
products
such
as
certain
foods,
soaps,
and
perfumes.
FDA
considers
d­
limonene
to
be
GRAS
as
a
food
additive
when
used
as
a
synthetic
flavoring
substance
and
adjuvant
(
21CFR
182.60).
d­
Limonene
is
not
registered
for
food
or
feed
crop
uses
as
an
active
ingredient,
but
can
be
used
on
compost
and
manure.

The
tolerance
exemptions
being
reassessed
in
this
document,
with
the
respective
citation
in
the
Code
of
Federal
Regulations
(
CFR),
and
the
use
patterns
as
an
active
and
inert
ingredient
are
listed
in
Table
1.
3
Table
1.
Tolerance
Exemptions
Being
Reassessed
in
this
Document
Tolerance
Exemption
Expression
CAS
No.
40
CFR
PC
Code
Use
Pattern
List
Classification
d­
Limonene
5989­
27­
5
Active
ingredient
180.539
079701
Used
in
insect­
repellent
tablecloths
and
in
insectrepellent
strips
used
in
food
or
feed­
handling
establishments
NA
Inert
Ingredient
180.910
and
180.930
(
formerly
180.1001(
c)
and
(
e))
a,
b
879701
"
Solvent,
fragrance"
4Bc
a
Residues
listed
in
40
CFR
180.910
are
exempt
from
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
applied
to
growing
crops
or
to
raw
agricultural
commodities
after
harvest
and
those
listed
in
40
CFR
180.930
are
exempt
from
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
applied
to
animals.
b
In
both
sections,
the
inert
ingredient
is
listed
as
"
d­
Limonene
(
CAS
Reg.
No.
5989­
27­
5)".
c
Inert
ingredients
are
categorized
into
four
lists
as
described
in
the
1987
and
1989
Policy
Statements.
List
4B
inert
ingredients
are
those
inerts
for
which
EPA
has
sufficient
information
to
reasonably
conclude
that
the
current
use
pattern
in
pesticide
products
will
not
adversely
affect
public
health
or
the
environment.

III.
Regulatory
Background
The
World
Health
Organization
published
a
document
in
1993
summarizing
safety
data
on
select
food
additives
and
naturally
occurring
toxicants
(
including
d­
limonene)
reviewed
by
the
Joint
FAO/
WHO
Expert
Committee
on
Food
Additives
(
JECFA)
(
WHO,
1993).
Based
on
information
from
various
studies,
the
JECFA
utilized
data
on
reduced
body
weights
in
male
rats
to
establish
an
acceptable
daily
intake
of
0­
1.5
mg/
kg
body
weight
for
d­
limonene.
The
committee
concluded,
however,
that
only
a
small
proportion
of
total
intake
would
likely
be
from
direct
additive
use
and
therefore
restricted
food
additive
intake
to
0.075
mg/
kg
body
weight/
day.
Note
that
in
a
subsequent
report
(
WHO,
1998),
a
later
panel
"
withdrew
the
existing
acceptable
daily
intake
...
and
in
its
place
allocated
"
not
specified"."

In
1994,
a
Reregistration
Eligibility
Decision
(
RED)
document
was
issued
by
EPA
to
ensure
that
as
an
active
ingredient
Limonene
can
be
used
without
posing
unreasonable
risks
to
human
health
or
the
environment.
(
Note
that
the
RED
was
written
on
"
Limonene"
and
lists
a
CAS
number
of
138­
86­
3,
which
is
actually
the
CAS
number
for

­
limonene,
although
the
RED
indicates
the
"
Trade
and
Other
Names"
is
dlimonene
Thus,
this
TRED
is
intended
to
be
for
the
CAS
number
5989­
27­
5,
which
is
the
CAS
Registry
No.
actually
assigned
for
d­
limonene.)
Both
human
health
and
environmental
risk
assessments
were
performed.
The
RED
reported
that
dietary
exposure
to
limonene
was
not
a
concern,
and
that
exposure
through
the
use
of
insecticide
sprays
or
animal
repellent
granules
could
result
in
skin
irritation/
sensitization
or
eye
irritation.
The
RED
also
reported
that
there
would
be
minimal
risks
to
birds,
mammals
and
aquatic
species
from
exposure
to
limonene
(
EPA,
1994).

In
1998,
a
Concise
International
Chemical
Assessment
Document
(
CICAD)
on
limonene
(
d­
limonene,
llimonene
and
d/
l­
limonene)
was
prepared
by
the
International
Programme
on
Chemical
Safety
[
a
cooperative
program
of
the
World
Health
Organization
(
WHO),
the
International
Labour
Organization,
and
the
United
Nations
Environment
Programme].
The
CICAD
was
based
primarily
on
a
review
prepared
in
1993
for
the
Nordic
Expert
Group,
as
well
as
a
review
performed
under
the
Nordic
Council
of
Ministers,
a
preliminary,
non
peer­
reviewed
information
source
on
environmental
exposure
and
effects,
and
database
4
searches
covering
the
years
1993­
1995.
Limonene
was
reported
to
be
a
skin
irritant
in
both
animals
and
humans
and
the
liver
was
reported
to
be
the
"
critical
organ"
in
animals,
that
is,
the
primary
target
organ
most
likely
to
show
adverse
effects.
The
report
concluded
that
"
food
is
believed
to
be
the
principal
source
of
exposure
(
96%)
to
limonene;
the
contribution
from
ambient
air
is
approximately
4%.
The
dermal
uptake
of
limonene
has
not
been
estimated."
To
determine
a
tolerable
intake
for
humans,
data
from
a
13­
week
oral­
gavage
study
in
the
male
rat
which
showed
increased
relative
liver
weights
was
utilized,
and
a
guidance
value
for
ingestion
was
calculated
to
be
0.1
mg/
kg
body
weight/
day
(
WHO,
1998).

d­
Limonene
was
included
in
a
report
submitted
to
the
EPA
HPV
Challenge
Program
by
the
Flavor
and
Fragrance
High
Production
Volume
Chemical
Consortia
(
The
Terpene
Consortium,
2002).
HPV
chemicals
are
those
that
are
manufactured
or
imported
into
the
U.
S.
in
production
volumes
greater
than
one
million
pounds
per
year.
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
toknow
about
the
potential
hazards
of
chemicals
found
in
their
environment,
their
homes,
their
workplace,
and
in
consumer
products.

IV.
Physical/
Chemical
Properties:

The
physical
and
chemical
properties
of
d­
limonene
are
provided
in
Table
2.

Table
2.
Physical/
Chemical
Properties
of
d­
Limonene
Structure
References:
NIOSH,
2001;
WHO,
1998
Molecular
formula
C10H16
Molecular
weight
136.2
g/
mole
Physical
state
colorless
liquid,
with
characteristic
mild
citrus
odor
Melting
point
­
75

C
Boiling
point
176

C
Solubility
in
water
13.8
mg/
L
at
25oC
pH
Not
applicable
Density/
Specific
Gravity
0.84
g/
mL
Vapor
Density
Relative
vapor
density
=
4.7
(
air
=
1)

Vapor
Pressure
0.4
kPa
at
14.4oC;
2
mm
Hg
at
20oC
Estimated
Octanol/
Water
Coefficient
log
Kow:
4.2
Dissociation
Constant
Not
applicable
Estimated
Henry's
Law
constant
34.8
kPa
m3/
mol
at
25oC
Estimated
Soil
Sorption
Coefficient
(
likely
to
sorb
based
on
log
P)
5
V.
Hazard
Assessment:

Key
toxicological
data
for
d­
limonene
are
provided
in
Table
3.
These
data
were
obtained
from
published
studies
in
peer
reviewed
journals
summarized
in
two
WHO
documents
(
WHO,
1993;
1998).
Data
cited
in
the
initial
tolerance
exemption
were
previously
reviewed
by
the
Agency
in
the
1994
RED.

Table
3.
Summary
of
Toxicity
Data
for
d­
Limonene
Acute
Toxicity
Test
Species
Route
of
Administration/
Doses
Results
Reference
Oral
LD50
Mouse
Oral
5600
mg/
kg
(
M)

WHO,
1993
6600
mg/
kg
(
F)

Rat
Oral
4400
mg/
kg
(
M)

5100
mg/
kg
(
F)

Dermal
LD50
Rabbit
Dermal
>
5000
mg/
kg
WHO,
1998
Inhalation
LC50
Studies
on
the
acute
inhalation
of
d­
limonene
in
laboratory
animals
have
not
been
identified.

Eye
Irritation
Rabbits
Eye
instillation
Irritation
to
eyes
observed
WHO,
1998
Dermal
Irritation
Guinea
pigs
Dermal
contact
Moderate
(
guinea
pigs)
WHO,
1998
Rabbits
Low
(
rabbits)

Rat
Irritant
at
high
concentrations
RED,
1994
Dermal
Sensitization
Guinea
pigs
May
cause
dermal
sensitization
RED,
1994
Freund's
Complete
Adjuvant
assay
d­
Limonene
in
unoxidized
form
did
not
cause
sensitization,
but
its
air­
oxidized
products
found
to
be
potent
contact
allergens
WHO,
1998
Subchronic
and
Chronic
Toxicity
16­
day
oral
Mice
Oral­
gavage:
0,
413,
825,
1650,
3300,
6600
mg/
kg­
bw/
d
NOAEL:
1650
mg/
kg­
bw/
d
LOAEL:
3300
mg/
kg­
bw/
d
Deaths
at
3300
and
6600
mg/
kg­
bw/
d,
but
no
compound­
related
clinical
signs
observed
in
mice
in
1650
mg/
kg­
bw
dose
group
that
lived
to
end
of
dosing,
plus
no
compound­
related
histopathologic
effects
(
NTP,
1990)
WHO,
1993,
1998
13­
week
oral
Mice
Oral­
gavage:
0,
125,
250,
500,
1000,
2000
mg/
kg­
bw/
d
NOAEL:
500
mg/
kg­
bw/
d
LOAEL:
1000
mg/
kg­
bw/
d
Reduced
body
weights
and
death,
plus
rough
hair
coats
and
decreased
activity
(
NTP,
1990)
WHO,
1993,
1998
Test
Species
Route
of
Administration/
Doses
Results
Reference
6
103­
week
oral
Mice
Oral­
gavage:
Males:
0,
250,
and
500
mg/
kg­
bw/
d;
Females:
0,
500,
1000
mg/
kg­
bw/
d
NOAEL:
250
mg/
kg­
bw/
d
(
male)
500
mg/
kg­
bw/
d
(
female)
LOAEL:
500
mg/
kg­
bw/
d
(
male)
1000
mg/
kg­
bw/
d
(
female)
In
males
dosed
at
500
mg/
kg­
bw/
d,
livers
exhibited
presence
of
cells
with
abnormal
numbers
of
nuclei
and
cytomegaly.
(
In
males
dosed
at
250
mg/
kg­
bw/
day,
lowest
dose
tested,
reduced
survival,
but
not
deemed
by
NTP
to
be
dose­
related.)
In
females,
decreased
survival
and
lower
body
weights
(
5
­
15%)
in
highest
dose
tested,
1000
mg/
kg­
bw,
but
no
treatment
related
clinical
signs
at
any
dose
tested
(
NTP,
1990)
WHO,
1993,
1998
16­
day
oral
Rats
Oral­
gavage:
0,
413,
825,
1650,
3300,
6600
mg/
kg­
bw/
d
NOAEL:
1650
mg/
kg­
bw/
d
LOAEL:
3300
mg/
kg­
bw/
d
Deaths
at
3300
and
6600
mg/
kg­
bw/
d,
but
no
clinical
signs
in
1650
mg/
kg­
bw
dose
group
or
lower,
and
no
compound­
related
histopathological
effects
seen
in
any
rats
(
NTP,
1990)
WHO,
1993,
1998
26­
day
oral
Rats
(
males
only)
Oral­
gavage:
0,
75,
150,
300
mg/
kg­
bw/
d
NOAEL:
undetermined
(
kidney)
150
mg/
kg­
bw/
d
(
liver)
LOAEL:
75
mg/
kg­
bw/
d
(
kidney)
300
mg/
kg­
bw/
d
(
liver)
At
lowest
dose
tested,
effects
on
kidneys
of
male
rats,
even
after
only
6
days;
in
addition,
increased
relative
kidney
and
liver
weights,
even
after
6
days,
measured
in
300
mg/
kg­
bw/
d
dosed
group,
but
not
in
150
mg/
kg­
bw/
d
group;
in
light
microscopy,
kidneys
showed
dose­
related
hyaline
droplet
formation,
as
well
as
granular
casts
in
outer
zone
of
medulla
and
chronic
nephrosis,
but
no
evident
alterations
observed
in
liver
sections,
even
at
highest
dose
tested
(
Kanerva
et
al.,
1987)
WHO,
1993,
1998
30­
day
oral
Rats
(
males
only)
Oral­
gavage:
400
mg/
kg­
bw/
d
LOAEL:
400
mg/
kg­
bw/
d
(
males
only)
At
only
dose
tested,
20­
30%
increase
in
amount
and
activity
of
different
liver
enzymes,
increase
in
relative
liver
weight,
and
decrease
in
cholesterol
levels;
no
histopathological
examinations
conducted
(
Ariyoshi
et
al.,
1975)
WHO,
1998
Test
Species
Route
of
Administration/
Doses
Results
Reference
7
13­
week
oral
Rats
(
males
only)
Oral­
gavage:
0,
2,
5,
10,
30,
75
mg/
kg­
bw/
d
NOAEL:
5
mg/
kg­
bw/
d
(
kidney)
30
mg/
kg­
bw/
d
(
liver)
LOAEL:
30
mg/
kg­
bw/
d
(
kidney)
75
mg/
kg­
bw/
d
(
liver)
For
kidneys,
"
incidence
and
severity
of
these
lesions
increased
slightly
at
10
mg
dlimonene
kg
body
weight
although
...
a
clear
91­
day
lowest­
observable
effect
(
LOEL)
was
produced
at
30
mg
dlimonene
kg
body
weight
(
P
<
0.01)".
For
liver,
no
differences
in
absolute
liver
weights,
and
increase
in
relative
liver
weights
statistically
significant
only
at
75
mg/
kg­
bw/
d,
but
no
histopathological
effects
observed
(
Webb
et
al.,
1989)
WHO,
1993,
1998
13­
week
oral
Rats
Oral­
gavage
0,
150,
300,
600,
1200,
2400
mg/
kg­
bw/
d
NOAEL:
undetermined
in
male
600
mg/
kg­
bw/
d
in
female
LOAEL:
150
mg/
kg­
bw/
d
in
male
1200
mg/
kg­
bw/
d
in
female
In
males,
kidneys
showed
nephropathy
at
all
doses,
with
severity
dose
related.
In
females,
at
1200
mg/
kg­
bw,
rough
hair
coats,
lethargy,
and
excessive
lacrimation
(
NTP,
1990)
WHO,
1993,
1998
103­
week
oral
Rats
Oral­
gavage
Males:
0,
75,
and
150
mg/
kg­
bw/
d;
Females:
0,
300,
600
mg/
kg­
bw/
d
NOAEL:
undetermined
(
male;
kidney)
150
mg/
kg­
bw/
d
(
male;
other
than
kidney,
no
adverse
effects
at
highest
dose
tested)
300
mg/
kg/
bw/
d
in
female
LOAEL:
75
mg/
kg­
bw/
d
(
male:
kidney)
undetermined
(
male;
other
than
kidney,
no
other
adverse
effects
at
highest
dose
tested)
600
mg/
kg­
bw/
d
in
female
In
males,
effects
in
kidneys
included
doserelated
increases
in
incidences
of
mineralization
and
epithelial
hyperplasia,
even
at
lowest
dose
tested;
however,
no
other
significant
adverse
effects
were
observed
by
NTP
in
males
dosed
at
150
mg/
kg­
bw/
d,
other
than
on
kidneys.
In
females,
at
600
mg/
kg­
bw/
d,
reduced
survival,
but
no
adverse
effects
in
low
dose
group,
300
mg/
kg­
bw/
day
(
NTP,
1990)
WHO,
1993,
1998
Toxicity
to
the
Kidney
of
Male
Rats:

Note
that
the
WHO
CICAD
report
(
1998)
listed
a
"
NOEL"
of
5
mg/
kg­
bw/
day,
based
on
pathological
8
formation
of
granular
casts
at
the
outer
zone
of
the
renal
medulla,
from
a
13­
week
oral­
gavage
study
in
the
rat
which
tested
males
only
(
Webb
et
al.,
1989).
This
would
appear
to
represent
the
lowest
NOAEL
for
dlimonene
but
the
authors
of
that
study
(
Webb
et
al.,
1989)
had
indicated
that
"
since
the
syndrome
is
dependent
on
the
presence
of
that
alpha2

­
globulin
[
in
male
rats],
species
such
as
humans,
mice,
dogs,
and
guinea­
pigs
that
do
not
produce
this
renal
protein
will
probably
not
develop
this
specific
toxicity
following
exposure
to
hydrocarbons
like
d­
limonene,"
and
further
that
"
this
toxicity
may
not
be
predictive
of
a
similar
response
in
humans."
The
EPA
Risk
Assessment
Forum
(
1991)
compiled
an
extensive
review
of
the
results
of
many
repeat
dosing
studies
of
various
chemicals
in
the
male
rat,
including
d­
limonene,
and
similarly
concluded
that
"
since
humans
appear
to
be
more
like
other
laboratory
animals
than
the
male
rat,
in
this
special
situation,
the
male
rat
is
not
a
good
model
for
assessing
human
risk."
Thus,
the
risk
assessments
in
this
TRED
will
not
further
consider
the
data
obtained
from
repeat
dosing
studies
causing
effects
in
the
kidney
of
the
male
rat.

Other
Toxic
Effects
in
Oral
Exposure
Studies
with
d­
Limonene,
including
to
the
Liver:

In
addition
to
effects
on
the
kidney
of
male
rats,
Webb
et
al.
(
1989)
reported
effects
on
the
liver.
Data
from
this
91­
day
subchronic
study
showed
increased
relative
liver
weights
and
relative
kidney
weights
to
be
statistically
significantly
at
75
mg/
kg­
bw/
d,
relative
to
total
body
weights,
although
there
were
no
statistically
significant
increases
in
absolute
weights
of
either
the
liver
or
the
kidney.
Based
on
the
information
reviewed
above
by
the
EPA
Risk
Assessment
Forum
(
1991),
the
effects
on
the
kidney
of
the
male
rat
are
not
considered
further.
However,
the
WHO
CICAD
report
(
1998)
did
utilize
the
increase
in
relative
liver
weights
from
the
Webb
et
al.
(
1989)
study
to
calculate
a
tolerable
intake,
but
that
report
utilized
a
NOEL
of
"
10
mg/
kg­
bw/
d"
of
d­
limonene,
and
inferred
that
the
d­
limonene
"
caused
increased
relative
liver
weight
at
30
and
75
mg/
kg
body
weight
per
day."
However,
the
increased
relative
liver
weight
was
not
found
to
be
statistically
significant
at
30
mg/
kg­
bw/
d,
with
the
relative
liver
weights
being
only
4.4%
greater
than
the
control,
while
75
mg/
kg­
bw/
d
was
statistically
significant,
but
still
only
8.3%
greater
than
the
controls.
While
Webb
et
al.
(
1989)
did
not
identify
a
specific
NOEL
or
NOAEL,
their
paper
stressed
that
there
were
no
treatment­
related
changes
during
the
in­
life
91­
day
dosing
period;
moreover,
the
incidence
and
type
of
gross
pathological
lesions
observed
at
necropsy,
and
the
cumulative
body
weight
gains,
feed
consumption,
and
food
efficiency
for
treated
males
did
not
differ
from
control
males.
In
addition,
the
light
microscopic
evaluation
of
liver
tissue
sections
stained
with
haematoxylin
and
eosin
of
the
treated
male
rats
revealed
no
histopathological
changes
despite
the
increased
relative
weights
of
the
liver.
Webb
et
al.
(
1989)
postulated
that
since
the
increased
relative
liver
weights
were
unaccompanied
by
any
changes
that
could
observed
using
light
microscopy,
it
was
likely
that
microsomal
induction
had
occurred,
since
mixed
function
oxidase
activity
was
known
to
increase
in
the
rat
liver
following
exposure
to
many
of
the
volatile
hydrocarbons.

An
earlier
d­
limonene
gavage
dosing
study
in
the
male
rat
was
conducted
over
a
shorter
dosing
period,
26
days,
and
also
achieved
statistical
significance
of
increased
relative
liver
weights,
but
at
a
dose
level
of
300
mg/
kg­
bw/
d,
and
did
not
find
statistically
significant
increases
at
150
mg/
kg­
bw/
d
(
Kanerva
et
al.,
1987).
The
statistically
significant
effects
were
noted
in
relative
liver
weights
after
only
6
days
of
dosing,
with
the
differences
being
even
more
pronounced
after
26
days
of
dosing
in
the
male
rat;
however,
note
that
even
after
26
days
of
dosing,
there
were
no
statistically
significant
differences
between
the
male
rats
dosed
at
150
mg/
kg­
bw/
d
and
the
male
rats
in
the
control.
In
addition,
microscopic
examination
of
liver
sections
revealed
no
differences
between
the
vehicle
control
(
corn
oil)
and
male
rats
which
had
been
dosed
with
dlimonene
at
either
treatment
level,
thus
Kanerva
et
al.
(
1987)
also
concluded
that
the
increased
relative
liver
weights
"
were
considered
to
be
a
probable
reflection
of
microsomal
induction,
since
it
is
known
that
certain
9
volatile
hydrocarbons
will
increase
mixed
function
oxidase
in
the
rat."

While
the
WHO
CICAD
report
(
1998)
utilized
a
"
NOEL"
of
10
mg/
kg­
bw/
d,
based
on
increased
relative
liver
weight
data
from
Webb
et
al.
(
1989),
an
earlier
WHO
report
(
1993)
had
reviewed
the
data
from
that
study,
Ariyoshi
et
al.
(
1975),
Kanerva
et
a.
(
1987),
and
the
NTP
(
1990)
study,
and
WHO
(
1993)
had
not
selected
the
relative
liver
weight
data
from
Webb
et
al.
(
1989)
as
the
key
toxic
endpoint.
Although
the
NTP
(
1990)
did
not
report
data
for
liver
weights,
the
WHO
(
1993)
document
evaluated
the
data
for
the
effects
on
the
liver
in
both
the
rat
and
mouse,
and
discussed
the
clinical
chemistry
data
for
the
liver
effects
reported
by
Ariyoshi
et
al.
(
1975),
and
then
concluded
the
following:
"
although
liver
lesions
were
not
associated
with
the
administration
of
d­
limonene
in
a
2­
year
study
in
rats
(
doses
up
to
150
mg/
kg
bw/
day
for
males;
doses
up
to
600
mg/
kg
bw/
day
for
females),
a
daily
gavage
dose
of
500
mg
d­
limonene/
kg
bw/
day
for
2
years
was
associated
with
an
increased
incidence
of
multinucleated
liver
hepatocytes
and
cytomegaly
in
male
mice.
The
NOEL
for
these
effects
was
250
mg/
kg
bw/
day
administered
by
gavage
to
male
mice
for
2
years."
Note
that
this
NOEL
for
the
male
mouse
cited
in
WHO
(
1993)
is
approximately
25
times
higher
than
the
10
mg/
kg­
bw/
d
based
on
increased
relative
liver
weights
in
the
male
rat
that
was
selected
by
WHO
(
1998)
to
calculate
the
tolerable
intake
for
humans.
Note
also
that
the
NTP
study
did
not
specifically
report
any
other
adverse
effects,
other
that
those
associated
with
the
effects
noted
in
the
kidneys,
and
especially
did
not
identify
any
adverse
effects
to
the
liver,
which
the
WHO
documents
have
identified
as
the
critical
organ,
including
at
150
mg/
kg­
bw/
d,
the
high
dose
tested
in
male
rats
over
the
2­
year
gavage
study.

The
OPP
HED
TOXicology
Science
Advisory
Council
(
TOXSAC)
prepared
a
guidance
document
concerning
hepatocellular
hypertrophy
on
October
21,
2002,
HED
Guidance
Document
#
G0201.
This
document
describes
a
weight­
of­
evidence
approach
to
characterizing
toxicity
to
the
liver
when
results
of
studies
show
an
increase
in
liver
size/
weight,
which
results
from
an
increase
in
the
size
of
liver
parenchymal
cells.
This
is
usually
an
indicator
something
has
changed
in
the
cell,
but
may
not
be
an
adverse
effect,
but
rather
only
that
xenobiotic
exposures
are
causing
an
increased
metabolic
response,
resulting
in
the
induction
of
the
metabolic
enzymes.
From
these
studies,
corroborating
evidence
of
toxicity
is
obtained
from
clinical
chemistry
and
or
histopathology.
"
Therefore,
the
dose
with
only
hepatocellular
hypertrophy
and/
or
liver
size/
weight
changes
should
be
considered
the
study
No­
Observable­
Adverse­
Effect­
Level
(
NOAEL).
The
Lowest­
Observable­
Adverse­
Effect­
Level
(
LOAEL)
for
the
study
should
be
the
dose
which
elicits
actual
hepatotoxicity
characterized
by
toxicologically
significant
changes
in
parameters
such
as
clinical
chemistry
and/
or
histopathology."
Clearly
the
Kanerva
et
al.
(
1987)
and
Webb
et
al.
(
1989)
studies
showed
increased
relative
liver
weights,
although
not
absolute
liver
weights,
but
in
each
study,
microscopic
examination
did
not
reveal
any
histopathological
changes.
While
neither
of
these
studies
evaluated
the
clinical
chemistry
parameters
identified
in
the
HED
Guidance
Document
#
G0201,
the
effects
at
26
days
reported
by
Kanerva
et
al.
(
1987)
for
the
male
rat
were
at
doses
higher
than
those
tested
for
2
years
by
NTP
(
300
vs
150
mg/
kg­
bw/
d,
respectively),
and
the
NTP
study
did
not
report
any
apparent
effects
on
the
liver.
Moreover,
the
increased
relative
liver
weights
reported
by
Webb
et
al.
(
1989)
after
13
weeks
were
statistically
significant
at
75
mg/
kg­
bw/
d,
but
were
only
8.3%
higher
than
those
in
the
controls.
Note
also
that
the
Kanerva
et
al.
(
1987)
study
only
utilized
5
male
rats
per
dose
group,
while
the
Webb
et
al.
(
1989)
utilized
more,
only
10
male
rats
were
tested
for
the
full
91­
day
dosing
period,
whereas
the
NTP
study
(
1990)
utilized
50
rats/
dose
group/
sex,
providing
an
additional
data
quality
aspect
to
this
latter
study.
Note
also
that
while
the
NTP
study
(
1990)
also
reported
adverse
effects
in
the
liver
of
male
mice
at
500
mg/
kg­
bw/
d,
specifically
cells
with
abnormal
numbers
of
nuclei
and
cytomegaly,
the
no
effects
were
noted
in
the
livers
of
female
rats
at
doses
of
600
mg/
kg­
bw/
d,
or
in
the
livers
of
female
mice
at
1000
mg/
kg­
bw/
d.
10
Thus,
the
critical
toxicological
endpoint
for
characterizing
the
effects
of
d­
limonene
would
not
be
the
effects
of
d­
limonene
on
the
kidney
of
the
male
rat.
Instead,
this
assessment
will
focus
on
the
liver,
but
not
on
data
showing
only
increased
relative
liver
weights
from
shorter
term
studies
in
the
male
rat,
in
the
absence
of
any
concomitant
histopathological
or
clinical
chemistry
effects.
Thus,
the
lowest
dose
at
which
an
effect
has
been
observed
suitable
for
use
as
the
short­
term
toxicity
endpoint
of
concern
(
exposure
scenarios
of
up
to
30
days)
is
the
LOAEL
of
400
mg/
kg/
day,
from
the
30­
day,
continuous
dosing
study
in
the
rat,
with
only
males
dosed
(
Ariyoshi
et
al.,
1975,
as
cited
in
WHO
1998).
(
Note
that
this
study
was
not
cited
in
the
WHO
(
1993)
or
RED
(
1994)
documents,
nor
the
HPV
submission.)
The
repeated
dosing
component
of
this
study
was
conducted
at
only
one
dosing
level,
following
single
treatments
at
200,
400,
800,
and
1200
mg/
kg,
to
select
doses
to
evaluate
the
efficacy
of
d­
limonene
to
solubilize
cholesterol
gallstones.
After
15
days
of
dosing
in
male
rats,
no
effects
were
observed
in
the
liver
parameters
measured,
but
after
30
days
of
repeated
dosing,
the
following
effects
were
observed:
relative
liver
weight
and
hepatic
phospholipid
content
had
slightly
increased;
the
liver
and
serum
cholesterol
values
had
decreased
by
49
and
8%,
respectively;
changes
in
the
phospholipid
fatty
acid
content
(
increases
in
palmitic,
lineoleic,
and
arachidonic
acids,
and
decrease
in
stearic
acid);
changes
in
enzyme
activity
(
aminopyrine
demethylase
and
aniline
hydrolase
were
increased
by
26
and
22%,
respectively);
and
changes
in
cytochrome
(
P­
450
and
b5
increased
by
31
and
30%,
respectively).
Thus,
repeated
dosing
at
400
mg/
kg
for
30
days
was
found
to
have
effects
on
various
parameters
in
the
liver
of
the
male
rat.
Note
that
Ariyoshi
et
al.
(
1975)
did
not
report
the
results
of
any
histopathological
examinations,
or
whether
any
were
performed.
(
Note
also
that
Table
3
shows
an
even
lower
effects
level
in
the
liver
of
the
male
rat
from
a
subchronic
study
of
approximately
the
same
duration,
with
a
NOAEL
of
150
mg/
kg­
bw/
d
and
an
LOAEL
of
300
mg/
kg­
bw/
d,
reported
by
Kanerva
et
al.
(
1987)
after
6
and
26
days
of
dosing,
but
as
already
stated,
these
data
are
for
relative
liver
weights
and
histopathological
examinations
of
liver
sections
did
reveal
any
evident
alterations
in
the
liver
of
the
male
rat.)

Toxicokinetics
and
Human
Volunteer
Inhalation
Exposures:

Falk­
Filipsson
et
al.
(
1993)
reported
on
a
study
to
assess
the
toxicokinetics
of
d­
limonene
in
human
volunteers,
exposed
by
inhalation
for
2
hours
each,
in
an
exposure
chamber.
The
exposures
were
at
concentrations
of
approximately
10,
225,
or
450
mg/
m3
d­
limonene.
The
relative
pulmonary
uptake
of
the
d­
limonene
was
high,
about
70%
of
the
amount
supplied.
The
blood
clearance
(
1.1
L/
kg/
hr)
indicates
that
the
d­
limonene
is
readily
metabolized,
although
a
long
half­
timer
in
the
blood
was
observed
during
the
slow
elimination
phase,
suggesting
some
accumulation
in
adipose
tissues.
After
the
end
of
the
exposure,
about
1%
of
the
total
d­
limonene
uptake
was
eliminated
unchanged
in
the
expired
air,
while
0.003%
was
eliminated
in
the
urine.
It
was
observed
that
there
was
a
decrease
in
the
vital
capacity
after
exposure,
in
those
exposed
at
the
highest
dose,
but
that
none
of
the
subjects
experienced
any
irritative
symptoms
nor
any
symptoms
related
to
the
central
nervous
system.

Mutagenicity/
Genotoxicity
and
Carcinogenicity:

The
WHO
documents
(
1993,
1998)
and
the
EPA
RED
(
1994)
report
that
on
the
basis
of
available
data,
there
is
no
evidence
that
d­
limonene
causes
any
genotoxic
or
mutagenic
effects.
In
addition,
those
documents,
which
also
include
the
data
from
the
NTP
1990
study,
cite
only
the
renal
lesions
and
kidney
tumors
in
male
rats
as
being
the
only
reported
incidences
of
carcinogenesis
due
to
d­
limonene;
moreover,
in
the
NTP
(
1990)
report,
the
conclusions
stated
that
the
results
indicated
there
was
"
no
evidence"
of
carcinogenic
activity
of
d­
limonene
in
the
female
rat,
as
well
as
in
either
the
male
or
female
mice.
The
WHO
(
1998)
document
also
reported
that
the
International
Agency
for
Research
on
Cancer
(
IARC)
has
11
classified
d­
limonene
in
"
Group
3
(
not
classifiable
as
to
its
carcinogenicity
to
humans)
based
on
a
lack
of
available
data
on
carcinogenicity
to
humans
and
limited
evidence
for
carcinogenicity
in
experimental
animals."
In
addition,
the
NTP
also
compiles
a
Report
on
Carcinogens
(
RoC),
which
is
the
U.
S.
government's
definitive
listing,
and
the
most
recent
listing,
the
10th
Report
(
December
2002)
did
not
list
dlimonene
(
or
"
limonene").

Reproductive/
Developmental
Effects:

The
1998
WHO
document
indicated
that
there
were
no
studies
of
the
reproductive
toxicity
which
had
been
identified,
but
presented
various
study
data
in
the
rat,
mouse
and
rabbit,
indicating
that
there
was
no
evidence
that
limonene
has
teratogenic
or
embryotoxic
effects
in
the
absence
of
maternal
effects.
In
addition,
a
study
was
reviewed
in
the
RED
(
1994),
and
based
on
the
data
presented,
it
is
concluded
that
dlimonene
is
not
a
developmental
toxicant,
because
in
the
rat
developmental
toxicity
study,
the
NOAEL
was
determined
to
be
250
mg/
kg/
day
for
both
maternal
and
developmental
toxicity.
There
were
small
decrements
in
maternal
body
weight
gain
at
500
mg/
kg/
day,
and
there
were
slight,
but
statistically
significant
and
dose­
dependent
increases
in
the
number
of
litters
and
fetuses
with
14
ribs,
instead
of
13
ribs,
at
500
mg/
kg/
day.
The
RED
considered
these
effects
to
be
variations
in
skeletal
formation,
not
accompanied
by
other
effects,
and
were
secondary
to
the
maternal
toxicity,
so
the
RED
concluded
these
effects
do
not
represent
a
concern
for
the
developmental
toxicity
of
limonene.

Maximum
Acceptable
Daily
Intake
Recommendations
/
Tolerable
Intake
Values:

The
WHO
(
1993)
document
was
the
Joint
Expert
Committee
on
Food
Additives
(
JECFA)
summary
report
concerning
the
use
of
d­
limonene
as
a
food
additive,
and
based
on
statistically
significantly
reduced
body
weights
in
male
rats
(
as
well
as
at
higher
NOAELs
in
female
rats,
male
and
female
mice,
and
female
rabbits),
concluded
the
following:

"
Based
on
the
significant
decreases
in
body
weight
gain
associated
with
administration
of
dlimonene
to
male
and
female
mice
and
rats
and
female
rabbits,
an
ADI
of
0
­
1.5
mg/
kg
bw
was
established
for
this
substance.
The
Committee
considered
the
known
natural
occurrence
and
food
additive
uses
of
d­
limonene,
and
concluded
that
only
a
small
proportion
of
total
intake
is
likely
to
be
derived
from
direct
additive
use.
The
Committee
therefore
recommended
that
food
additive
intake
be
restricted
to
75

g/
kg
bw/
day
[
i.
e.,
0.075
mg/
kg
bw/
day],
which
represents
5%
of
the
maximum
ADI
for
d­
limonene."

It
should
be
noted
that
the
WHO
(
1998)
reported
that
a
subsequent
JECFA
meeting
had
withdrawn
this
1993
ADI
value,
and
in
its
place
allocated
"
not
specified,"
and
"
the
establishment
of
an
acceptable
daily
intake
expressed
in
numerical
form
was
not
deemed
necessary."

Special
Considerations
for
Infants
and
Children
At
this
time,
there
is
no
concern
for
potential
sensitivity
to
infants
and
children.
Based
on
the
data
from
the
study
reviewed
in
the
RED
(
EPA,
1994)
and
the
various
teratogenicity
and
embryotoxicity
studies
reviewed
in
the
WHO
study
(
1998),
it
is
now
again
concluded
that
limonene
is
not
a
developmental
toxicant.
Therefore,
a
safety
factor
analysis
has
not
been
used
to
assess
the
risk.
For
the
same
reason,
the
additional
tenfold
safety
factor
is
unnecessary,
and
has
been
removed.

Toxicity
Endpoint
Selection:
1
NTP
(
1990)
did
report
effects
in
male
rats
at
150
mg/
kg­
bw/
d,
but
the
report
provided
explanations
for
each
effect,
as
follows:
interstitial
cell
tumors
in
the
testis
occurred
with
a
positive
trend,
but
are
a
commonly
occurring
neoplasm
in
aging
male
F344
rats,
and
"
not
considered
to
be
related
to
chemical
exposure;"
mononuclear
cell
leukemia
occurred
in
a
positive
trend,
but
"
were
not
significantly
different
from
that
in
vehicle
controls
and
were
not
considered
to
be
related
to
d­
limonene
administration;"
three
squamous
cell
papillomas
or
carcinomas
occurred
in
high
dose
male
rats,
but
the
incidence
was
not
significantly
different
from
vehicle
controls
and
was
within
the
range
of
historical
incidences
in
NTP
studies,
and
"
thus
these
tumors
were
not
considered
related
to
d­
limonene
administration;"
and
cataracts
were
observed
at
increased
incidences
in
high
dose
group
male
and
female
rats,
but
"
these
changes
are
not
believed
to
be
related
to
the
administration
of
d­
limonene
but
rather
to
the
proximity
of
animal
cages
to
the
light
source
in
the
animal
room."

12
For
this
assessment
of
d­
limonene,
there
are
no
dermal
or
inhalation
toxicological
studies
in
animals
and
no
dermal
absorption
studies
available
in
the
existing
literature.
Therefore,
to
assess
short­
term
dermal
and
inhalation
exposures,
an
oral
LOAEL
was
used.
The
dermal
dose
was
conservatively
converted
to
an
equivalent
oral
dose
using
a
100%
dermal
and
inhalation
absorption
factor.
The
oral
toxicological
LOAEL
endpoint
of
400
mg/
kg­
day
was
used
(
Ariyoshi
et
al.
1975).
This
LOAEL
was
based
on
liver
effects
(
increased
enzymes
and
liver
weights)
observed
in
a
30­
day
rat
oral
(
gavage)
study
(
WHO,
1998).
Since
this
endpoint
is
based
on
a
LOAEL,
an
additional
safety
factor
of
3X
was
applied
to
the
uncertainty
factor
of
100
(
10
for
interspecies
extrapolation
and
10
for
intraspecies
variation).
A
Margin
of
Exposure
(
MOE)
of
300
or
greater
is
protective
for
these
short­
term
risk
assessments.

To
assess
the
long­
term
dermal
and
inhalation
exposures,
an
oral
NOAEL
of
150
mg/
kg­
bw/
d
was
selected
from
a
103­
week
oral
gavage
study
in
the
male
rat
(
NTP,
1990).
At
this
dose,
there
were
pronounced
effects
on
the
kidney,
but
the
EPA
Risk
Assessment
Forum
(
1991)
has
indicated
these
effects
on
the
kidney
of
male
rats
are
not
appropriate
for
risk
characterization.
Because
the
NTP
report
did
not
identify
any
other
adverse
effects
on
the
male
rats
at
this
highest
dose
tested1,
especially
on
the
liver
parameters
evaluated,
this
dose
is
being
utilized
as
the
NOAEL,
with
the
clear
understanding
that
there
were
effects
on
the
kidney
of
the
male
rat,
but
these
renal
effects
would
not
likely
be
observed
in
any
other
species
or
sex.
In
view
of
the
absence
of
significant
effects,
other
than
in
the
kidney,
in
the
male
rats
at
150
mg/
kg­
bw/
d,
this
NOAEL
was
selected
and
deemed
to
be
"
conservative"
(
i.
e.,
health­
protective),
because
the
other
NOAEL
values
from
the
NTP
(
1990)
study
were
even
higher
for
the
other
test
animals,
250
mg/
kg­
bw/
d
for
the
male
mice,
300
mg/
kg­
bw/
d
for
the
female
rats,
and
500
mg/
kg­
bw/
d
for
the
female
mice.
Note
also
that
other
studies
had
reported
effects
at
lower
doses,
but
the
effect
reported
was
increased
relative
liver
weights
(
Kanerva
et
al.,
1987;
Webb
et
al.
1989),
but
these
effects
occurred
in
the
absence
any
histopathological
changes
observed
with
light
microscopy
and
there
were
no
measured
enzyme
induction
changes
reported
for
clinical
chemistry
parameters.
In
addition,
there
were
larger
sample
sizes
in
the
NTP
study,
thus,
based
on
the
weight­
of­
evidence,
the
Agency
believes
that
the
NTP
data
are
more
reliable
for
assigning
an
NOAEL.
Since
this
toxicity
endpoint
selected
for
long­
term
exposures
is
a
NOAEL,
rather
than
the
LOAEL
which
was
selected
for
short­
term
exposures,
an
additional
uncertainty
factor
is
not
necessary.

VI.
Exposure
Assessment
Exposure
to
d­
limonene
may
occur
through
the
use
of
certain
pesticide
products,
including
insect
repellents
and
dog
and
cat
repellents.
In
addition,
exposure
may
occur
naturally
through
different
foods,
or
through
FDA­
approved
GRAS
uses
such
as
in
food
products,
soaps,
and
perfumes.
13
Residential
dermal
exposure
to
d­
limonene
as
an
active
ingredient
in
various
pesticide
products
was
examined
for
this
risk
assessment.
Postapplication
exposure
to
pesticide
products
containing
d­
limonene
as
the
active
ingredient
were
not
examined.
It
was
assumed
that
dermal
exposure
following
application
of
the
pesticide
products
containing
d­
limonene
would
be
minimal
considering
the
high
vapor
pressure
of
dlimonene
(
see
Table
2).
Chemical
residues
would
be
expected
to
dissipate
relatively
soon
after
application,
diminishing
the
possibility
of
potential
exposure
to
persons
after
application.

The
exposure
scenarios
chosen
for
the
active
ingredient
risk
assessment
were
based
on
the
anticipated
use
patterns
and
current
labeling
for
d­
limonene
pesticide
products
(
see
Table
4).
In
addition,
application
rates
were
estimated
based
on
information
provided
on
the
product
labels
and
these
assumptions
are
listed
in
Table
4.
The
average
body
weight
of
an
adult
(
70
kg)
was
assumed.
The
oral
LOAEL
of
400
mg/
kg/
day
was
used
for
short­
term
exposures,
while
an
oral
NOAEL
of
150
mg/
kg/
day
was
used
for
the
long­
term
exposures.
A
margin
of
exposure
(
MOE)
was
calculated
for
each
scenario,
and
when
the
toxicity
endpoint
of
concern
was
a
LOAEL,
the
MOE
of
concern
was
300.

The
short­
term
handler
MOEs
range
from
a
low
of
81
for
the
application
of
pet
dips
to
a
high
of
7,300
for
the
application
of
liquid
pesticides
with
a
watering
can
(
see
Table
4).
The
short­
term
MOEs
for
scenarios
with
the
inert
ingredient
range
from
a
low
of
420
for
painting
to
a
high
of
3,300,000
for
back­
spraying
(
see
Table
5).
The
long­
term
consumer
product
use
MOEs
range
from
a
low
of
200
for
general
purpose
cleaner
inhalation
exposure
to
a
high
of
46,580
for
aerosol
spray
can
inhalation
exposure.
More
detailed
information,
such
as
the
exposure
and
dose
calculations,
are
provided
in
Appendix
A.

For
exposure
to
products
containing
d­
limonene
as
an
inert
ingredient,
the
Pesticide
Inert
Risk
Assessment
Tool
(
PIRAT,
test
version)
was
used
to
estimate
handler
dermal
exposure
(
Versar,
2004).
This
tool
is
based
on
weight
fractions
of
inert
ingredients
in
pesticide
products.
For
this
risk
assessment,
it
was
assumed
that
exposure
would
be
to
the
following
formulations:
pressurized
liquids,
ready­
to­
use
liquids,
and
emulsifiable
and
soluble
concentrates.
All
product
uses
for
these
formulations
were
examined
and
the
90th
percentile
default
weight
fractions
were
assumed.
In
addition,
a
100%
dermal
and
inhalation
absorption
factors
were
used
to
convert
doses
to
equivalent
oral
doses.
Default
application
rates
were
provided
for
several
scenarios
in
PIRAT,
based
on
either
professional
judgement
or
the
Science
Advisory
Council
for
Exposure
Policy
11
(
SAC,
2001).
If
a
default
application
rate
was
not
provided,
it
was
assumed
that
10
lb
of
product
per
acre
(
0.00023
lb/
ft2)
was
applied.

The
scenarios,
application
rates,
areas
treated
or
amounts
used
and
calculated
MOEs
are
provided
in
Table
5.
MOEs
for
inert
uses
ranged
from
a
low
of
420
for
ready­
to­
use
outdoor
paints/
stains
that
are
applied
by
airless
sprayer
to
a
high
of
3,300,000
for
emulsifiable
concentrates
applied
using
a
backpack
sprayer.
Exposure
outputs
from
the
PIRAT
model
are
provided
in
Appendix
B.

In
terms
of
consumer
use
exposure
to
products
containing
d­
limonene,
the
Consumer
Exposure
Module
(
CEM)
(
Versar,
1999)
was
used
to
determine
the
possible
residential
exposure
to
d­
limonene.
The
exposure
scenario
examined
was
the
use
of
a
general
purpose
cleaner
assuming
a
weight
fraction
range
of
12.5%
to
25%.
Table
6
provides
the
CEM
dermal
MOE
estimates.
Exposure
output
information
from
the
CEM
model
is
provided
in
Appendix
C.
Using
the
oral
NOAEL
of
150
mg/
kg­
day
and
assuming
100%
dermal
absorption,
the
MOE
was
calculated
to
be
2,600.

To
assess
inhalation
exposure,
two
scenarios
representing
the
expected
highest
exposures
for
the
overall
use
pattern,
were
evaluated
for
this
assessment:
(
1)
general
purpose
cleaner,
and
(
2)
aerosol
spray
can.
In
14
both
scenarios
it
was
assumed
that
the
use
takes
place
indoors.
Using
the
Consumer
Exposure
Module
of
the
E­
FAST
model,
inhalation
MOEs
of
200
for
the
general
purpose
cleaner,
and
124,200
for
the
aerosol
can
scenario
have
been
calculated.
See
Table
6
for
a
breakdown
of
the
inhalation
MOE
calculation,
and
see
Appendix
C
for
more
details
of
the
model
run.
15
Table
4.
Residential
Handler
Risks
Due
to
Exposure
to
d­
Limonene
as
an
Active
Ingredient
Exposure
Scenario
Assumptions
for
estimating
product
application
rate
Percent
active
ingredient
Calculations
of
product
application
rate
(
AR)
Application
Rate
Area
Treated
or
Amount
Handled
Dailya
Baseline
Dermal
MOEb
Loading/
Applying
Granulars
by
Hand
From
product
label
B
apply
1
lb/
800
ft2
4
AR
=
(
1
lb/
800
ft2)*
0.04
0.00005
lb
ai/
ft2
1000
ft2/
day
1,300
Mixing/
loading/
applying
emulsifiable
concentrates
with
a
watering
can
From
product
label,

max
application
rate
is
8
fl.
oz
and
5.6
lb
ai/
gallon
78.2
AR
=
5.6
lb
ai/
gal
*
1
gal/
128
oz
*
8
oz/
1000
ft2
0.00035
lb
ai/
ft2
1000
ft2/
day
7,300
Applying
RTU
(
Ready
to
Use)
Formulations
via
Pump­
Trigger
Spray
Assume
0.125
gallons
of
product
applied
per
day
and
assume
density
is
1.0
g/
mL
5.8
AR
=
(
1.0
g/
mL
*
0.0022
lb/
g
*

3785
mL/
gal)
*

0.058
0.48
lb
ai/
gallon
0.125
gal/
day
2,100
Applying
RTU
Formulations
via
Shampoo
Average
size
of
shampoo
bottle
is
12
oz;
use
½
bottle
when
shampooing
pet;

assume
density
is
1.0
g/
mL
5
AR
=
(
1.0
g/
mL
*
1000mL/
L
*

1L/
33.8
oz
*

1000
mg/
g
*
6
oz/
day)
*
0.05
8,876
mg
ai/
day
NA
320
Applying
RTU
Formulations
via
Dip
From
product
label
B
use
1.5
oz/
gallon
of
water;
assume
density
is
1.0
g/
mL
78.2
AR
=
(
1.0
g/
mL
*
1000mL/
L
*

1L/
33.8
oz
*

1000
mg/
g
*

1.5
oz/
day)
*

0.782
34,704
mg
ai/
day
NA
81
a
Amount
handled
per
day
values
are
EPA
estimates
of
amount
treated
based
on
revised
Residential
SOPs
(
2/
01).

b
Baseline
Dermal
MOE
=
LOAEL
(
400
mg/
kg/
day)
/
dermal
daily
dose
(
mg/
kg/
day),
where
dermal
dose
=
daily
unit
exposure
(

g/
lb
ai)
x
application
rate
x
amount
handled
per
day
x
conversion
factor
(
if
needed)
/
body
weight
(
70
kg
adult).
16
Table
5.
Residential
Handler
Risks
Due
to
Exposure
to
d­
Limonene
as
an
Inert
Ingredient
Formulation
Type
Application
method
Crop
Treated
Application
Rate
Area
treated
or
Amount
Used
Dermal
MOE
Emulsifiable
Concentrate
Low
pressure
handwand
Turf,
Garden,
Trees,
Outdoor
Perimeter
Treatment
0.00023
lb/
ft2
1000
ft2
170,000
Crack
and
Crevice
0.12
lb/
gal
0.5
gal/
day
660,000
Backpack
Turf,
Garden,
Trees,
Outdoor
Perimeter
Treatment
0.00023
lb/
ft2
1000
ft2
3,300,000
Hose­
end
sprayer
Turf
0.00023
lb/
ft2
20000
ft2
28,000
Garden
and
Trees
1000
ft2
550,000
Pressurized
liquid
Aerosol
Crack
and
Crevice
0.094
gal/
day
NA
56,000
Outdoor
paint
and
stain
0.28
gal/
day
8,100
Ready
to
Use
liquid
Pump­
trigger
Turf
and
Garden
1.0
gal/
day
NA
2,300
Crack
and
Crevice
0.50
gal/
day
NA
10,000
Paintbrush
Trees
and
Outdoor
Paint
and
Stains
1.0
gal/
day
NA
2,200
Airless
sprayer
Outdoor
Paint
and
Stains
15
gal/
day
NA
420
Backpack
5
gal/
day
NA
20,000
Low
pressure
handwand
5
gal/
day
NA
1,000
Crack
and
Crevice
0.50
gal/
day
NA
10,000
Pump­
trigger
Crack
and
Crevice
0.13
gal/
day
NA
18,000
Low
pressure
handwand
0.50
gal/
day
NA
10,000
Soluble
Concentrate
Low
pressure
handwand
Turf
0.00023
lb/
ft2
1000
ft2
410,000
Garden
and
Trees
120,000
Crack
and
Crevice
490,000
Backpack
Turf,
Garden,
Trees
and
Outdoor
Perimeter
Treatment
0.00023
lb/
ft2
1000
ft2
2,400,000
Hose­
end
sprayer
Turf
0.00023
lb/
ft2
20000
ft2
21,000
Garden
and
Trees
1000
ft2
410,000
Low
pressure
handwand
Crack
and
Crevice
0.12
lb/
gal
0.5
gal/
day
490,000
Outdoor
Perimeter
Treatment
0.00023
lb/
ft2
1000
ft2
120,000
17
Table
6.
Summary
of
Consumer
Dermal
and
Inhalation
Exposure
Scenarioa
Weight
Fractions
Dermal
Doseb
(
mg/
kg­
day)
Dermal
MOEc
Inhalation
Doseb
(
mg/
kg­
day)
Inhalation
MOE
General
Purpose
Cleaner
0.125
5.77e­
02
2,600
7.53E­
01
200c
Aerosol
Spray
Can
0.000734
NAe
NA
3.22E­
03
124,200d
a
This
model
run
was
developed
using
the
Office
of
Pollution,
Prevention,
and
Toxics
(
OPPT).
The
general
purpose
cleaner
scenario
was
run
with
Standard
New
Chemicals
Program
assumptions
and
defaults.
While
the
aerosol
spray
can
scenario
was
modified
to
assess
60
days
of
use
over
a
year.
b
Modeled
for
chronic
dose
rates.
c
MOE
=
NOAEL
(
150
mg/
kg­
day)/
Average
Daily
Dose
(
mg/
kg/
day).
d
MOE
=
LOAEL
(
400
mg/
kg­
day)/
Average
Daily
Dose
(
mg/
kg/
day).
e
NA
=
Not
available.
EFAST
Consumer
Exposure
Module
does
not
have
a
dermal
exposure
scenario
for
aerosol
paint.

VII.
Dietary
(
Food)
Exposure
Screening­
level
dietary
modeling
was
performed
to
determine
the
potential
exposure
for
d­
limonene
in
the
food
supply
as
a
result
of
applications
of
a
pesticide
product
containing
d­
limonene
as
an
inert
ingredient.
The
following
assumptions
were
used
for
the
DEEM
modeling:

­
Actual
crop­
specific
residue
data
for
active
ingredients
can
be
utilized
as
surrogate
data
for
inert
ingredient
residue
levels
(
including
secondary
residues
in
meat,
milk,
poultry
and
eggs)
­
Inert
ingredients
are
used
on
all
crops
and
100%
of
all
crops
are
"
treated"
with
inert
ingredients
­
No
adjustment
made
for
%
of
inert
in
formulation,
application
rate,
or
multiple
applications
of
different
active
ingredient
formulations
­
Considers
only
preharvest
applications
Dietary
modeling
was
performed
utilizing
the
highest
established
tolerance
level
residue
for
each
commodity.

Table
7.
Estimated
Chronic
Dietary
Exposurea
and
Riskb
for
a
Generic
Inert
Ingredient
Population
Subgroupc
Estimated
Exposure,
mg/
kg/
day
MOE
U.
S.
Population
(
total)
0.120
1250
All
infants
(<
1
year)
0.245
610
Children
(
1­
2
years)
0.422
360
Children
(
3­
5
years)
0.310
480
Children
(
6­
12
years)
0.174
860
Youth
(
13­
19
years)
0.100
1500
Adults
(
20­
49
years)
0.087
1720
Adults
(
50+
years)
0.086
1740
18
Females
(
13­
49
years)
0.087
1720
a
Exposure
estimates
are
based
on
highest­
tolerance­
level
residues
of
high­
use
active
ingredients
for
all
food
forms,
including
meat,
milk,
poultry,
and
eggs.
b
MOE
=
NOAEL
(
150
mg/
kg/
day)
/
Estimated
Exposure
(
mg/
kg/
day)
c
Only
representative
population
subgroups
are
shown.

For
chronic
dietary
assessments,
a
NOAEL
of
150
mg/
kg­
bw/
d
was
selected,
based
on
an
103­
week
oral
gavage
study
in
the
male
rat.
For
all
populations
addressed,
the
MOEs
for
d­
limonene
were
greater
than
the
MOE
of
concern
of
100.

VIII.
Drinking
Water
Considerations
d­
Limonene
is
only
somewhat
soluble
in
water
(
13.8
mg/
L)
and
has
an
estimated
octanol/
water
partition
coefficient
of
4.2.
d­
Limonene
is
expected
to
rapidly
volatilize
from
water
to
the
atmosphere,
with
an
estimated
half­
life
for
volatilization
from
a
model
river
of
3.4
hr,
although
adsorption
to
sediment
and
suspended
organic
matter
may
attenuate
the
rate
of
this
process.
Based
on
these
data,
it
is
unlikely
that
dlimonene
will
occur
in
drinking
water
sources
resulting
from
any
of
the
registered
and
proposed
uses
as
an
active
ingredient
or
when
used
as
an
inert
ingredient
as
discussed
above.

IX.
Aggregate
Assessment
d­
Limonene
is
naturally­
occurring
in
citrus
and
certain
fruits,
vegetables,
meats
and
spices.
And
dlimonene
is
classified
by
the
US
FDA
as
a
GRAS
food
additive.
It
is
present
in
baked
goods,
ice
cream
products,
gelatins,
puddings
and
chewing
gum
at
levels
ranging
from
68
to
2300
ppm
from
the
direct
food
additive
use.

Given
the
physical/
chemical
properties
of
d­
limonene,
it
is
unlikely
that
d­
limonene
will
occur
in
drinking
water
sources.
However,
the
Agency
has
conducted
screening­
level
exposure
assessments
for
dietary
exposures
as
a
result
of
agricultural
applications,
and
residential
exposures.
Various
screening­
level
models
were
used
to
estimate
some
of
the
existing
levels
of
exposure
that
could
occur.
To
assure
protectiveness,
these
models
create
estimates
that
are
deliberately
intended
to
over­
estimate
exposure.

As
an
inert
ingredient,
d­
limonene
can
be
applied
to
agricultural
crops.
So,
the
Agency's
screening
level
dietary
assessment
was
performed
based
on
a
use
pattern
that
considered
uses
on
all
crops.
The
generic
modeling
was
performed
using
data
derived
from
chemicals
that
are
solids.
But,
for
d­
limonene,
the
vapor
pressure
is
2
mm
Hg,
thus
indicative
of
significant
evaporation.

One
of
the
greatest
uncertainties
of
using
this
generic
dietary
assessment
for
a
volatile
chemical
such
a
dlimonene
is
the
potential
for
d­
limonene
to
enter
the
food
supply
as
a
result
of
agricultural
applications.
Based
on
the
vapor
pressure
(
1)
it
is
unlikely
that
any
significant
amount
of
residues
of
a
volatile
chemical
would
remain
on
the
surface
of
the
plant
or
edible
commodity
and
(
2)
it
is
also
unlikely
that
residues
of
such
a
volatile
chemical
would
be
incorporated
into
the
raw
agricultural
commodity
that
is
eventually
harvested.
While
there
is
a
logic
to
this
rationale,
the
Agency
also
acknowledges
a
great
deal
of
uncertainty
on
this
issue.

Generally,
the
Agency
has
advocated
a
position
that
if
a
pesticide
chemical
is
used
on
a
food
crop,
residues
19
of
that
chemical
substance
are
assumed
to
be
present
unless
there
is
compelling
data
to
the
contrary.
Such
data
could
be
a
radiolabelled
uptake
study
of
sufficient
sensitivity
to
ascertain
whether
or
not
the
residues
exist
in
the
edible
commodity.
The
Agency
is
unaware
of
such
data
for
a
chemical
such
as
d­
limonene.
Therefore,
the
generic
dietary
exposure
estimates
used
in
this
assessment
are
overly
conservative
for
a
chemical
such
as
d­
limonene,
and
the
estimated
MOEs
could
be
even
larger.

To
judge
the
potential
aggregate
exposures
for
d­
limonene
the
Agency
is
performing
an
aggregate
assessment
for
two
residential
scenarios:
use
in
a
cleaning
product,
and
RTU
formulations
via
shampoo.
The
cleaning
product
represents
the
use
of
d­
limonene
as
an
inert
ingredient
in
a
product
that
could
be
used
in
and
around
the
home.
Cleaning
products
also
tend
to
be
used
in
a
repetitive
manner,
and
are
more
of
a
chronic
type
of
scenario.
The
RTU
formulation
represents
the
use
of
d­
limonene
as
an
active
ingredient
in
a
product
that
could
be
used
in
and
around
the
home.
The
RTU
formulation
also
represents
a
very
shortterm
scenario
that
could
be
measured
in
minutes
that
is
of
a
non­
repetitive
nature.

Given
that
these
two
scenarios
bracket
the
inert
and
active
uses,
as
well
as
the
short­
term
and
more
chronic
types
of
scenarios,
and
that
these
two
scenarios
have
the
lowest
residential
MOEs
estimated
for
d­
limonene,
all
other
aggregate
MOEs
should
be
greater
than
the
target
MOE.

Table
8:
Aggregate
MOEs
Scenario
Type
of
Assessment
Exposure
(
dietary
+
residential)
(
mg/
kg/
day)
MOE
RTU
via
shampoo
short­
term
LOAEL
=
400
mg/
kg/
day
target
MOE
is
300
0.12
+
1.25
=
1.37
290
0.06
+
1.25
=
1.31
305
general
cleaner
long­
term
NOAEL
=
150
mg/
kg/
day
target
MOE
is
100
0.12
+
0.753
=
0.873
171
The
MOE
of
290
is
less
than
the
target
MOE
of
300.
However,
as
previously
discussed
the
dietary
exposures
are
considered
to
be
much
over­
estimated
due
to
the
volatile
nature
of
d­
limonene.
If
the
dietary
exposure
is
divided
by
2
(
0.12/
2
=
0.06),
then
the
MOE
is
305.
This
indicates
that
the
driver
for
the
aggregate
exposure
is
not
the
dietary
exposure
that
occurs
as
a
result
of
applications
of
a
pesticide
product,
but
the
residential
exposure,
which
in
and
of
itself
is
considered
to
be
over­
estimated.

X.
Risk
Characterization
d­
Limonene
is
naturally­
occurring
in
food
and
is
classified
by
the
US
FDA
as
a
GRAS
food
additive.
It
is
present
in
baked
goods,
ice
cream
products,
gelatins,
puddings
and
chewing
gum
at
levels
ranging
from
68
to
2300
ppm.
d­
Limonene
is
expected
to
rapidly
volatilize
from
dry
soil,
wet
soil
and
water,
therefore
exposure
through
the
drinking
water
routes
is
considered
very
unlikely.
Exposure
through
the
dietary
route
as
a
result
of
application
of
a
pesticide
product
is
considered
to
be
also
unlikely
due
to
the
volatile
nature
of
d­
limonene.
The
dietary
estimates
presented
are
considered
to
be
over­
estimates
for
a
chemical
such
as
dlimonene
The
driver
for
aggregate
exposure
for
d­
limonene
is
the
residential
exposure.
20
In
this
assessment
forty
nine
exposure
scenarios
were
evaluated.
Of
these
forty
nine
,
and
considering
only
the
residential
exposure
component,
only
one
scenario
(
the
dermal
exposure
pet
dip
scenario)
resulted
in
an
MOE
that
was
less
than
the
target
MOE
of
300.
The
MOE
for
residential
exposures
from
the
use
of
pet
dips
containing
limonene
was
calculated
to
be
81.
While
this
is
less
than
the
target
MOE
of
300,
several
factors
need
to
be
considered
when
interpreting
this
MOE,
including:

°
The
assessment
is
based
on
the
OPP
Health
Effects
Division's
Standard
Operating
Procedures
(
SOP)
for
Residential
Exposure
Assessments.
In
that
pet
dip
SOP,
the
Agency
states:
"
The
uncertainties
associated
with
this
assessment
stem
from
assumptions
regarding
amount
of
chemical
handled
and
the
percentage
of
which
humans
are
exposed.
The
estimated
doses
are
believed
to
be
reasonable
bounding
estimates
based
on
professional
judgement."

°
The
toxicity
endpoint
chosen
for
this
assessment
was
a
30­
day
feeding
study
(
oral­
gavage)
administered
to
rats.
It
was
from
a
1975
study
and
was
the
lowest
(
i.
e.
most
conservative)
of
the
NOAELs
and
LOAELs
in
the
liver
in
oral
studies
conducted
for
30
days
or
less.
There
are
also
16­
day
studies,
both
rat
and
mice,
in
which
there
were
NOAELs
of
1650
mg/
kg/
day.
However,
all
of
these
studies
are
multi­
day
(
continuously
dosing
endpoint)
which
was
then
compared
to
a
pet
dip
scenario
for
which
the
Agency
believes
that
it
is
most
likely
that
there
will
only
be
a
single
event
exposure
for
less
than
an
hour's
duration.

°
The
dermal
absorption
rate
for
this
assessment
is
assumed
to
be
100%,
which
may
be
conservative
for
this
particular
chemical.

°
There
is
only
one
product
currently
registered
with
this
use
pattern,
EPA
Reg.
No.
4758­
144.
On
the
label
in
question,
there
is
a
specific
recommendation
that
users
wear
rubber
gloves
while
performing
the
pet
dip
activity.
The
Agency
does
not
require
personal
protective
equipment
for
residential
use
labels;
however,
the
Agency
also
does
not
typically
request
that
registrants
remove
PPE
from
their
existing
labels,
when
the
use
of
such
PPE
is
protective
for
users.

Taken
together,
these
factors
make
a
strong
case
that
the
resulting
estimate
significantly
overestimate
exposures
and
risks
for
this
pet
dip
scenario.

Several
uncertainties
and
limitations,
in
addition
to
the
ones
mentioned
above
for
the
pet
dip
scenario,
are
associated
with
this
assessment.
For
the
granular,
emulsifiable
concentrate
and
ready­
to­
use
liquid
formulation
scenarios,
uncertainties
exist
from
the
use
of
surrogate
exposure
data
(
PHED
data)
and
from
the
assumptions
regarding
the
amount
of
chemical
that
is
handled.
However,
it
is
believed
that
the
doses
estimated
based
on
these
assumption
are
reasonable
central
tendency
to
high­
end
estimates
based
on
observations
from
chemical­
specific
studies
and
professional
judgement
(
SAC,
2001).

The
Agency
believes
that
these
considerations
are
sufficient
to
determine
that
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
exposure
to
limonene
when
considering
dietary
exposure
and
all
other
non­
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.

XI.
Environmental
Fate/
Ecotoxicity
21
d­
Limonene
is
only
somewhat
soluble
in
water
(
13.8
mg/
L),
and
it
is
somewhat
resistant
to
aerobic
and
anaerobic
biodegradation
in
water
and
soil.
Based
on
its
water
solubility
and
estimated
octanol/
water
partition
coefficient
(
4.2),
its
predicted
soil
adsorption
coefficient
indicates
that
it
will
display
low
mobility
in
soil.
However,
it
is
expected
to
rapidly
volatilize
from
both
dry
and
moist
soil
to
the
atmosphere,
although
adsorption
to
soil
may
attenuate
the
rate
of
this
process.
Once
in
the
atmosphere,
limonene
is
expected
to
rapidly
undergo
gas­
phase
oxidation
reactions
with
photochemically
produced
hydroxyl
radicals,
ozone,
and
at
night
with
nitrate
radicals,
with
calculated
half­
lives
for
these
processes
on
the
order
of
a
two
hours
or
less.

Toxicity
studies
have
been
performed
with
both
the
technical
form
of
d­
limonene
and
its
formulated
products,
as
well
as
products
which
contain
d­
limonene
as
an
inert
ingredient.
Based
on
the
data
from
these
studies,
d­
limonene
has
been
shown
to
be
practically
nontoxic
to
birds
and
slightly
toxic
to
freshwater
species,
both
fish
and
invertebrates.
Studies
on
rats
have
also
shown
d­
limonene
to
be
practically
non­
toxic
to
mammals
(
EPA,
1994).

XII.
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."
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
d­
limonene
and
any
other
substances,
and
d­
limonene
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
d­
limonene
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
the
Agency'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/.

XIII.
References
Ariyoshi
T,
M
Arakaki,
K
Ideguchi,
Y
Ishizuka,
K
Noda,
H
Ide.
1975.
Studies
on
the
metabolism
of
dlimonene
(
p­
mentha­
1,8­
diene).
III.
Effects
of
d­
limonene
on
the
lipids
and
drug­
metabolizing
enzymes
in
rat
livers.
Xenobiotica.
5:
33­
38.

Falk­
Filipsson
A,
A
Löf,
M
Hagberg,
EW
Hjelm,
Z
Wang.
1993.
d­
Limonene
exposure
to
humans
by
inhalation:
Uptake,
distribution,
elimination,
and
effects
on
the
pulmonary
function.
Jour
Toxicol
Environ
Health.
38:
77­
88.

Kanerva
RL,
GM
Ridder,
FR
Lefever,
CL
Alden.
1987.
Comparison
of
short­
term
renal
effects
due
to
oral
administration
of
decalin
or
d­
limonene
in
young
adult
male
Fischer­
344
rats.
Food
Chem
Toxicol.
25:
345­
353.

National
Institute
for
Occupational
Safety
and
Health
(
NIOSH).
2001.
d­
Limonene.
International
Chemical
Safety
Cards
(
ICSC):
0918.
Retrieval
date
03/
17/
04.
22
http://
www.
cdc.
gov/
niosh/
ipcsneng/
neng0918.
html
National
Toxicology
Program
(
NTP).
1990.
Toxicology
and
Carcinogenesis
Studies
of
d­
Limonene
(
CAS
No.
5989­
27­
5)
in
F344/
N
Rats
and
B6C3F1
Mice
(
Gavage
Studies).
NTP
TR
347.
U.
S.
Department
of
Health
and
Human
Services,
Public
Health
Service,
National
Institutes
of
Health.
NIH
Publication
No.
90­
2802.

Report
on
Carcinogens
(
RoC),
Tenth
Edition;
U.
S.
Department
of
Health
and
Human
Services,
Public
Health
Service,
National
Toxicology
Program,
December,
2002.
http://
ehp.
niehs.
nih.
gov/
roc/
toc10.
html
The
Flavor
and
Fragrance
High
Production
Volume
Consortia;
The
Terpene
Consortium.
2002.
Robust
Summaries
and
Test
Plan
for
Monoterpenes.
HPV
Challenge
Program:
AR201­
13756
A
and
B.
Retrieval
date
03/
17/
04.
http://
www.
epa.
gov/
chemrtk/
monoterp/
c13756tc.
htm
Science
Advisory
Council
(
SAC)
for
Exposure
(
2001)
Policy
11:
Revised
Residential
SOP
Assumptions
(
February
22,
2001).

U.
S.
EPA.
Risk
Assessment
Forum.
1991.
Alpha
2u­
Globulin:
Association
with
Chemically
Induced
Renal
Toxicity
and
Neoplasia
in
the
Male
Rat.
EPA/
625/
3­
91/
019F.

U.
S.
EPA.
1994.
Reregistration
Eligibility
Decision
(
RED):
Limonene.
Office
of
Prevention,
Pesticides,
and
Toxic
Substances
(
7508W).
EPA
738­
R­
94­
034.

U.
S.
EPA.
1998.
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.

Versar,
Inc.
1999.
Consumer
Exposure
Module
(
CEM),
Version
1.2.
Prepared
for
the
Economics,
Exposure
and
Technology
Division
of
the
Office
of
Pollution
Prevention
and
Toxic
Substances.
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
efast.
htm
Versar,
Inc.
2004.
Pesticide
Inert
Risk
Assessment
Tool
(
PIRAT),
Test
Version.
Prepared
for
the
Office
of
Pesticide
Programs.
In
review.
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
pirat.
htm
Webb
DR,
GM
Ridder,
CL
Alden.
1989.
Acute
and
subchronic
nephrotoxicity
of
d­
limonene
in
Fischer
344
rats.
Food
Chem
Toxicol.
27:
639­
649.

World
Health
Organization
(
WHO).
1993.
Toxicological
Evaluation
of
Certain
Food
Additives
and
Naturally
Occurring
Toxicants.
International
Programme
on
Chemical
Safety.
39th
Meeting
of
the
Joint
FAO/
WHO
Expert
Committee
on
Food
Additives
(
JECFA).
Retrieval
date
4/
12/
2004.
http://
www.
inchem.
org/
documents/
jecfa/
jecmono/
v30je01.
htm
World
Health
Organization
(
WHO).
1998.
Concise
International
Chemical
Assessment
Document
No.
5:
Limonene.
International
Programme
on
Chemical
Safety.
Prepared
by:
Dr.
A.
Falk
Filipsson,
National
Institute
for
Working
Life;
Mr.
J.
Bard;
Ms.
S.
Karlsson,
National
Chemicals
Inspectorate.
Retrieval
date
4/
12/
2004.
http://
www.
inchem.
org/
documents/
cicads/
cicads/
cicad05.
htm
APPENDIX
A
Active
Ingredient
Residential
Handler
Exposure
24
Exposure
Scenario
Application
Rate
Area
Treated
Daily
Dermal
Unit
Exposure
(
mg/
lb
ai)
Dermal
Exposure
(
mg/
day)
a
Dermal
Dose
(
mg/
kg­
day)
Dermal
MOE
Mixer/
Loader/
Applicator
Mixing/
Loading/
Applying
Emulsifiable
Concentrates
with
a
Watering
Can
0.00035
lb
ai/
ft2
1000
ft2/
day
11
3.9
0.055b
7,300
Loading/
Applying
Granulars
by
Hand
0.00005
lb
ai/
ft2
1000
ft2/
day
430
22
0.31b
1,300
Applying
Ready
to
Use
Formulations
via
Trigger­
Pump
Sprayer
0.48
lb
ai/
gallon
0.125
gal/
day
220
13
0.19b
2,100
Applying
Ready
to
Use
Formulations
via
Shampoo
8876
mg
ai/
day
NA
NA
NA
1.3c
320
Applying
Ready
to
Use
Formulations
via
Dip
34704
mg
ai/
day
NA
NA
NA
5c
81
a
Dermal
Exposure
=
(
Application
rate)*(
Area
treated
daily)*(
Dermal
unit
exposure)
b
Dermal
Dose
=
(
Dermal
exposure)/(
Adult
body
weight)
c
Dermal
Dose
=
(
Application
rate)*(
Fraction
exposed,
0.01)/(
Adult
body
weight)
25
APPENDIX
B
Inert
Ingredient
Residential
Handler
Exposure
26
PiRat
Handler
Report
for
Formulation
Type
Emulsifiable
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.34E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
1
Scenario
#
2
Scenario
#
3
Product
Use:
turf
turf
turf
Application
Method:
low
pressure
handwand;
MLAP
backpack:
MLAP
sprinkling
can;
MLAP
Dermal
PDR
(
mg/
kg/
day):
3.25E­
03
1.23E­
04
7.24E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
100.00
Low
9­
80
reps
5.10
Low
9­
11
reps
30.00
Low
8
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
120000
3300000
550000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
2
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
3
assumed
based
on
hose­
end;
SOPs
*
Modified
by
user
27
PiRat
Handler
Report
for
Formulation
Type
Emulsifiable
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.34E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
4
Scenario
#
5
Scenario
#
6
Product
Use:
turf
garden
garden
Application
Method:
hose
end
sprayer;
MLAP
low
pressure
handwand;
MLAP
backpack:
MLAP
Dermal
PDR
(
mg/
kg/
day):
1.45E­
02
2.41E­
03
1.23E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
30.00
Low
8
reps
100.00
Low
9­
80
reps
5.10
Low
9­
11
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
2.00E+
04
ft2/
day
(
full
broadcast)
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
28000
170000
3300000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
upper
percentile
lawn
size
(
SAC
Policy
11)

Scenario
#
2
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
3
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
*
Modified
by
user
28
PiRat
Handler
Report
for
Formulation
Type
Emulsifiable
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.34E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
7
Scenario
#
8
Scenario
#
9
Product
Use:
garden
garden
trees
Application
Method:
sprinkling
can;
MLAP
hose
end
sprayer;
MLAP
low
pressure
handwand;
MLAP
Dermal
PDR
(
mg/
kg/
day):
7.24E­
04
7.24E­
04
2.41E­
03
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
30.00
Low
8
reps
30.00
Low
8
reps
100.00
Low
9­
80
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
550000
550000
170000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
assumed
based
on
hose­
end;
SOPs
Scenario
#
2
SAC
Policy
11
Scenario
#
3
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
*
Modified
by
user
29
PiRat
Handler
Report
for
Formulation
Type
Emulsifiable
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.34E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
10
Scenario
#
11
Scenario
#
12
Product
Use:
trees
trees
trees
Application
Method:
backpack:
MLAP
sprinkling
can;
MLAP
hose
end
sprayer;
MLAP
Dermal
PDR
(
mg/
kg/
day):
1.23E­
04
7.24E­
04
7.24E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
5.10
Low
9­
11
reps
30.00
Low
8
reps
30.00
Low
8
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
3300000
550000
550000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
2
assumed
based
on
hose­
end;
SOPs
Scenario
#
3
SAC
Policy
11
*
Modified
by
user
30
PiRat
Handler
Report
for
Formulation
Type
Emulsifiable
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.34E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
13
Scenario
#
14
Scenario
#
15
Product
Use:
crack
&
crevice
outdoor
perimeter
treatment
outdoor
perimeter
treatment
Application
Method:
low
pressure
handwand;
MLAP
low
pressure
handwand;
MLAP
backpack:
MLAP
Dermal
PDR
(
mg/
kg/
day):
1.21E­
06
2.41E­
03
1.23E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
100.00
Low
9­
80
reps
100.00
Low
9­
80
reps
5.10
Low
9­
11
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
gal
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
0.50
gal/
day
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
330000000
170000
3300000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
SAC
Policy
11
Scenario
#
2
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
3
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
*
Modified
by
user
31
PiRat
Handler
Report
for
Formulation
Type
Pressurized
Liquid
Functional
Use:
Fragrance
(
deodorant,
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
3.00E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
1
Scenario
#
2
Product
Use:
outdoor
spray
paints/
stains
crack
&
crevice
Application
Method:
aerosol;
APP
aerosol;
APP
Dermal
PDR
(
mg/
kg/
day):
4.93E­
02
7.09E­
03
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
220.00
Medium
15­
30
reps
220.00
Medium
15­
30
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
Application
Rate:
0.28
gal/
day
9.40E­
02
gal/
day
Fraction
Exposed:
N/
A
N/
A
Amount
used:
N/
A
N/
A
Density
(
lb/
gal):
8.00
8.00
MOE:
8100
56000
Exposure
Frequency
(
yrs)
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
LADD
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
D)/
BW
Assumptions:
Scenario
#
1
assumed
to
use
three
12­
oz.
cans
per
event
(
90th
percentile
amount
of
spray
Scenario
#
2
assumed
to
use
one
12
oz.
cans
1
aerosol
cans
per
event;
SAC
Policy
11
*
Modified
by
user
32
PiRat
Handler
Report
for
Formulation
Type
Ready
to
Use
Liquid
Functional
Use:
Fragrance
(
deodorant,
perfume,
odor
masking
agent,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.00E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
1
Scenario
#
2
Scenario
#
3
Product
Use:
turf
garden
trees
Application
Method:
pump­
trigger;
APP
pump­
trigger;
APP
paintbrush;
APP
Dermal
PDR
(
mg/
kg/
day):
0.18
0.18
0.18
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
220.00
Medium
15­
30
reps
220.00
Medium
15­
30
reps
230.00
Medium
14­
15
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
1.00
gal/
day
(
spot)
1.00
gal/
day
(
spot)
1.00
mg/
kg/
day
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
N/
A
N/
A
N/
A
Density
(
lb/
gal):
8.00
8.00
8.00
MOE:
2300
2300
2200
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
D)/
BW
Assumptions:
Scenario
#
1
professional
judgement
Scenario
#
2
professional
judgement
Scenario
#
3
assumed
to
be
highest
amt.
individual
would
brush
on;
SAC
Policy
11
*
Modified
by
user
33
PiRat
Handler
Report
for
Formulation
Type
Ready
to
Use
Liquid
Functional
Use:
Fragrance
(
deodorant,
perfume,
odor
masking
agent,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.00E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
4
Scenario
#
5
Scenario
#
6
Product
Use:
outdoor
paints/
stains
outdoor
paints/
stains
outdoor
paints/
stains
Application
Method:
paintbrush;
APP
airless
sprayer;
APP
backpack;
APP
Dermal
PDR
(
mg/
kg/
day):
0.18
0.95
2.04E­
02
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
230.00
Medium
14­
15
reps
79.00
High
15
reps
5.10
Low
9­
11
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
1.00
gal/
day
15.00
gal/
day
5.00
gal/
day
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
N/
A
N/
A
N/
A
Density
(
lb/
gal):
8.00
8.00
8.00
MOE:
2200
420
20000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
D)/
BW
Assumptions:
Scenario
#
1
assumed
to
use
2
1­
gal.
cans
based
on
90th
percentile
value
of
8
gal.
of
latex
Scenario
#
2
assumed
to
use
three
5­
gal.
cans,
based
on
coverage
rate
of
200
ft2/
gal;
and
a
Scenario
#
3
assumed
value
based
on
idea
that
more
would
be
used
by
this
method
than
by
*
Modified
by
user
34
PiRat
Handler
Report
for
Formulation
Type
Ready
to
Use
Liquid
Functional
Use:
Fragrance
(
deodorant,
perfume,
odor
masking
agent,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
7.00E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
7
Scenario
#
8
Scenario
#
9
Product
Use:
outdoor
paints/
stains
crack
&
crevice
crack
&
crevice
Application
Method:
low
pressure
handwand;
APP
pump­
trigger;
APP
low
pressure
handwand;
APP
Dermal
PDR
(
mg/
kg/
day):
0.40
2.20E­
02
4.00E­
02
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
100.00
Low
9­
80
reps
220.00
Medium
15­
30
reps
100.00
Low
9­
80
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
5.00
gal/
day
0.13
gal/
day
0.50
gal/
day
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
N/
A
N/
A
N/
A
Density
(
lb/
gal):
8.00
8.00
8.00
MOE:
1000
18000
10000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
D)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
D)/
BW
Assumptions:
Scenario
#
1
assumed
value
based
on
idea
that
more
would
be
used
by
this
method
than
by
Scenario
#
2
one
16
oz
bottle;
SAC
Policy
11
Scenario
#
3
based
on
professional
judgement;
SAC
Policy
11
*
Modified
by
user
35
PiRat
Handler
Report
for
Formulation
Type
Soluble
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
9.88E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
1
Scenario
#
2
Scenario
#
3
Product
Use:
turf
turf
turf
Application
Method:
low
pressure
handwand;
MLAP
backpack;
MLAP
sprinkling
can;
MLAP
Dermal
PDR
(
mg/
kg/
day):
9.86E­
04
1.66E­
04
9.74E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
100.00
Low
9­
80
reps
5.10
Low
9­
11
reps
30.00
Low
8
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
410000
2400000
410000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
2
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
3
assumed
based
on
hose­
end;
SOPs
*
Modified
by
user
36
PiRat
Handler
Report
for
Formulation
Type
Soluble
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
9.88E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
4
Scenario
#
5
Scenario
#
6
Product
Use:
turf
garden
garden
Application
Method:
hose
end
sprayer;
MLAP
low
pressure
handwand;
MLAP
backpack;
MLAP
Dermal
PDR
(
mg/
kg/
day):
1.95E­
02
3.25E­
03
1.66E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
30.00
Low
8
reps
100.00
Low
9­
80
reps
5.10
Low
9­
11
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
2.00E+
04
ft2/
day
(
full
broadcast)
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
21000
120000
2400000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
upper
percentile
lawn
size
(
SAC
Policy
11)

Scenario
#
2
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
3
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11;

*
Modified
by
user
37
PiRat
Handler
Report
for
Formulation
Type
Soluble
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
9.88E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
7
Scenario
#
8
Scenario
#
9
Product
Use:
garden
garden
trees
Application
Method:
sprinkling
can,
MLAP
hose
end
sprayer;
MLAP
low
pressure
handwand;
MLAP
Dermal
PDR
(
mg/
kg/
day):
9.74E­
04
9.74E­
04
3.25E­
03
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
30.00
Low
8
reps
30.00
Low
8
reps
100.00
Low
9­
80
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
1000.00
ft2/
day
1000.00
ft2/
day
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
410000
410000
120000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
assumed
based
on
hose­
end;
SOPs
Scenario
#
2
SAC
Policy
11
Scenario
#
3
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
*
Modified
by
user
38
PiRat
Handler
Report
for
Formulation
Type
Soluble
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
9.88E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
10
Scenario
#
11
Scenario
#
12
Product
Use:
trees
trees
trees
Application
Method:
backpack;
MLAP
sprinkling
can;
MLAP
hose
end
sprayer;
MLAP
Dermal
PDR
(
mg/
kg/
day):
1.66E­
04
9.74E­
04
9.74E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
5.10
Low
9­
11
reps
30.00
Low
8
reps
30.00
Low
8
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
1000.00
ft2/
day
Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
2400000
410000
410000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
2
assumed
based
on
hose­
end;
SOPs
Scenario
#
3
SAC
Policy
11
*
Modified
by
user
39
PiRat
Handler
Report
for
Formulation
Type
Soluble
Concentrate
Functional
Use:
Fragrance
(
perfume,
fragrance)
Toxicity
Value:
400
Body
Weight:
70.0
kg
Weight
Fraction:
9.88E­
03
Duration:
Short
Term
Absorption
Value:
100
%

Scenario
#
13
Scenario
#
14
Scenario
#
15
Product
Use:
crack
&
crevice
outdoor
perimeter
treatment
outdoor
perimeter
treatment
Application
Method:
low
pressure
handwand;
MLAP
low
pressure
handwand;
MLAP
backpack;
MLAP
Dermal
PDR
(
mg/
kg/
day):
1.62E­
06
3.25E­
03
1.66E­
04
Inhalation
PDR
(
mg/
kg/
day)
N/
A
N/
A
N/
A
Dermal
Unit
Exposure
(
mg/
lb):
100.00
Low
9­
80
reps
100.00
Low
9­
80
reps
5.10
Low
9­
11
reps
Inhalation
Unit
Exposure
(
mg/
lb):
N/
A
N/
A
N/
A
Application
Rate:
2.30E­
04*
lb/
gal
2.30E­
04*
lb/
ft2
2.30E­
04*
lb/
ft2
Fraction
Exposed:
N/
A
N/
A
N/
A
Amount
used:
0.50
gal/
day
1000.00
ft2/
day
(
spot)
1000.00
ft2/
day
(
spot)

Density
(
lb/
gal):
N/
A
N/
A
N/
A
MOE:
250000000
120000
2400000
Exposure
Frequency
(
yrs)
N/
A
N/
A
N/
A
Exposure
Duration
(
yrs)
N/
A
N/
A
N/
A
Averaging
Time
(
yrs)
N/
A
N/
A
N/
A
LADD
N/
A
N/
A
N/
A
Cancer
Risk
N/
A
N/
A
N/
A
Dose
Calculation:
Scenario
#
1
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
2
PDR=(
UE*
AR*
WF*
A)/
BW
Scenario
#
3
PDR=(
UE*
AR*
WF*
A)/
BW
Assumptions:
Scenario
#
1
SAC
Policy
11
Scenario
#
2
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
Scenario
#
3
1,000
ft2/
day
assumed
to
be
equivalent
to
5
gal/
day;
SAC
Policy
11
*
Modified
by
user
40
APPENDIX
C
Inert
Ingredient
Consumer
Use
Residential
Exposure
41
CEM
Inputs
ID
Number:
Unknown
Product:
d­
limonene
Chemical
Name:
d­
limonene
Scenario:
General
Purpose
Cleaner
Population:
Adult
Molecular
Weight
(
g/
mole):
136.2
Weight
Fraction
­
Median
(
unitless):
0.125
Weight
Fraction
­
90%
(
unitless):
0.25
Dermal
Inputs
Frequency
of
Use
­
Body
(
events/
yr):
300
SA/
BW
­
Body
(
cm2/
kg):
15.6
Amount
Retained
/
Absorbed
to
Skin
(
g/
cm2­
event):
3.6e­
05
Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
2.08e+
04
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
42
CEM
Dermal
Exposure
Estimates
ID
Number:
Unknown
Scenario:
General
Purpose
Cleaner
Population:
Adult
Years
of
Use
(
years):
57
SA/
BW
Body
(
cm2/
kg):
15.6
Frequency
of
Use
(
events/
year):
300
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
4.39e­
02
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
5.77e­
02
2.08e+
04
Acute
ADRpot
(
mg/
kg­
day)
1.40e­
01
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)

Note:
75
years
=
2.738e+
04
days
pot
­
potential
dose
Note:
The
general
Agency
guidance
for
assessing
short­
term,
infrequent
events
(
for
most
chemicals,
an
exposure
of
less
than
24
hours
that
occurs
no
more
frequently
than
monthly)
is
to
treat
such
events
as
independent,
acute
exposures
rather
than
as
chronic
exposure.
Thus,
estimates
of
long­
term
average
exposure
like
ADD
or
ADC
may
not
be
appropriate
for
use
in
assessing
risks
associated
with
this
type
of
exposure
pattern.
(
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.
April
1998
43
CEM
Inputs
ID
Number:
Unknown
Product:
Unknown
Chemical
Name:
d­
Limonene
Scenario:
General
Purpose
Cleaner
Population:
Adult
Molecular
Weight
(
g/
mole):
136.2
Vapor
Pressure
(
torr):
2
Weight
Fraction
­
Median
(
unitless):
0.125
Weight
Fraction
­
90%
(
unitless):
0.125
Inhalation
Inputs
Frequency
of
Use
(
events/
yr):
300
Years
of
Use:
57
Mass
of
Product
Used
per
Event
­
Median
(
g):
61.5
Mass
of
Product
Used
per
Event
­
90%
(
g):
123
Inhalation
Rate
During
Use
(
m3/
hr):
0.55
Duration
of
Use
­
Median
(
hours/
event):
0.667
Inhalation
Rate
After
Use
(
m3/
hr):
0.55
Duration
of
Use
­
90%
(
hours/
event):
1.42
Zone
1
Volume
(
m3):
20
Whole
House
Volume
(
m3):
369
Air
Exchange
Rate
(
air
exchanges/
hr):
0.45
Body
Weight
(
kg):
71.8
Activity
Patterns
User:
1111111221542467422744411
Start
Time:
7
Non­
User:
1111111132442477422744411
Room
of
Use:
2.
Kitchen
Hour:
0
6
12
18
Dermal
Inputs
Frequency
of
Use
­
Body
(
events/
yr):
300
SA/
BW
­
Body
(
cm2/
kg):
15.6
Amount
Retained
/
Absorbed
to
Skin
(
g/
cm2­
event):
3.6e­
05
Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
2.08e+
04
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
CEM
Inhalation
Exposure
Estimates
ID
Number:
Unknown
Scenario:
General
Purpose
Cleaner
Population:
Adult
44
Inhalation
Rate
(
m3/
day):
0.55
Years
of
Use
(
years):
57
Body
Weight
(
kg):
71.8
Frequency
of
Use
(
events/
year):
300
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
5.72e­
01
2.74e+
04
LADCpot
(
mg/
m3)
3.11e+
00
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
7.53e­
01
2.08e+
04
ADCpot
(
mg/
m3)
4.10e+
00
2.08e+
04
Acute
ADRpot
(
mg/
kg­
day)
1.75e+
00
1.00e+
00
Cppot
(
mg/
m3)
1.30e+
02
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)
LADC
­
Lifetime
Average
Daily
Concentration
(
mg/
m3)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)
ADC
­
Average
Daily
Concentration
(
mug/
m3)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)
Cp
­
Peak
Concentration
(
mg/
m3)

Note:
75
years
=
2.738e+
04
days
pot
­
potential
dose
Note:
The
general
Agency
guidance
for
assessing
short­
term,
infrequent
events
(
for
most
chemicals,
an
exposure
of
less
than
24
hours
that
occurs
no
more
frequently
than
monthly)
is
to
treat
such
events
as
independent,
acute
exposures
rather
than
as
chronic
exposure.
Thus,
estimates
of
long­
term
average
exposure
like
ADD
or
ADC
may
not
be
appropriate
for
use
in
assessing
risks
associated
with
this
type
of
exposure
pattern.
(
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.
April
1998
45
CEM
Inputs
ID
Number:
Unknown
Product:
Unknown
Chemical
Name:
None
Scenario:
Aerosol
Paint
Population:
Adult
Molecular
Weight
(
g/
mole):
136.2
Vapor
Pressure
(
torr):
2
Weight
Fraction
­
Median
(
unitless):
0.000734
Weight
Fraction
­
90%
(
unitless):
0.000734
Inhalation
Inputs
Frequency
of
Use
(
events/
yr):
60
Years
of
Use:
11
Mass
of
Product
Used
per
Event
­
Median
(
g):
227
Mass
of
Product
Used
per
Event
­
90%
(
g):
738
Inhalation
Rate
During
Use
(
m3/
hr):
0.55
Duration
of
Use
­
Median
(
hours/
event):
0.333
Inhalation
Rate
After
Use
(
m3/
hr):
0.55
Duration
of
Use
­
90%
(
hours/
event):
1
Zone
1
Volume
(
m3):
20
Whole
House
Volume
(
m3):
369
Air
Exchange
Rate
(
air
exchanges/
hr):
0.45
Body
Weight
(
kg):
71.8
Portion
of
Aerosol
in
Air
(
unitless):
0.01
Activity
Patterns
User:
1
1
1
1
1
1
1
2
3
5
5
4
2
4
6
7
4
2
2
7
4
4
4
1
Start
Time:
9
Non­
User:
1
1
1
1
1
1
1
1
3
2
4
4
2
4
7
7
4
2
2
7
4
4
4
1
Room
of
Use:
5.
Utility
Room
Hour:
0
6
12
18
Dermal
Inputs
There
are
no
Dermal
inputs
for
this
scenario.

Avg.
Time,
LADDpot,
LADCpot
(
days):
2.74e+
04
Avg.
Time,
ADDpot,
ADCpot
(
days):
4.02e+
03
Avg.
Time,
ADRpot,
Cppot
(
days):
1.00e+
00
46
CEM
Inhalation
Exposure
Estimates
ID
Number:
Unknown
Scenario:
Aerosol
Paint
Population:
Adult
Inhalation
Rate
(
m3/
day):
0.55
Years
of
Use
(
years):
11
Body
Weight
(
kg):
71.8
Frequency
of
Use
(
events/
year):
60
Exposure
Units
Result
AT
(
days)

Chronic
Cancer
LADDpot
(
mg/
kg­
day)
4.72e­
04
2.74e+
04
LADCpot
(
mg/
m3)
2.57e­
03
2.74e+
04
Chronic
Non­
Cancer
ADDpot
(
mg/
kg­
day)
3.22e­
03
4.02e+
03
ADCpot
(
mg/
m3)
1.75e­
02
4.02e+
03
Acute
ADRpot
(
mg/
kg­
day)
6.24e­
02
1.00e+
00
Cppot
(
mg/
m3)
5.76e+
00
1.00e+
00
LADD
­
Lifetime
Average
Daily
Dose
(
mg/
kg­
day)
LADC
­
Lifetime
Average
Daily
Concentration
(
mg/
m3)

ADD
­
Average
Daily
Dose
(
mg/
kg­
day)
ADC
­
Average
Daily
Concentration
(
mg/
m3)

ADR
­
Acute
Dose
Rate
(
mg/
kg­
day)
Cp
­
Peak
Concentration
(
mg/
m3)

Note:
75
years
=
2.738e+
04
days
pot
­
potential
dose
Note:
The
general
Agency
guidance
for
assessing
short­
term,
infrequent
events
(
for
most
chemicals,
an
exposure
of
less
than
24
hours
that
occurs
no
more
frequently
than
monthly)
is
to
treat
such
events
as
independent,
acute
exposures
rather
than
as
chronic
exposure.
Thus,
estimates
of
long­
term
average
exposure
like
ADD
or
ADC
may
not
be
appropriate
for
use
in
assessing
risks
associated
with
this
type
of
exposure
pattern.
(
Methods
for
Exposure­
Response
Analysis
for
Acute
Inhalation
Exposure
to
Chemicals
(
External
Review
Draft).
EPA/
600/
R­
98/
051.
April
1998