Document ID: EPA-HQ-OPP-2002-0280-0011
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-10-02T04:00Z

Page
1
of
15
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
April
8,
2002
MEMORANDUM
FROM:
Kathryn
Boyle,
CoChair
IIFG
and
Kerry
Leifer,
CoChair
IIFG
TO:
Robert
Forrest,
Chief
Minor
Use,
Inerts,
and
Emergency
Response
Branch
SUBJECT:
January
8,
2002
Meeting
of
the
IIFG
Decision
Memo
Please
find
attached
the
Inert
Ingredient
Focus
Group
recommendations
for
the
inert
ingredients
associated
with
the
"plant
and
animal
byproducts"
grouping.
Page
2
of
15
INERT
INGREDIENT
FOCUS
GROUP
DECISION
DOCUMENT
for
the
Plant
and
Animal
By­
Product
Grouping
Chemical
Name:
Several,
see
below.

Category:
Plant
and
Animal
Byproducts
CAS
Reg.
No.:
Several,
see
below.

Introduction:

The
meeting
of
the
Inert
Ingredient
Focus
Group
(IIFG)
to
discuss
the
"plant
and
animal
byproducts"
grouping
was
held
on
January
8,
2002.
Focus
Group
members
in
attendance
were:
Kathryn
Boyle
(RD),
Kerry
Leifer
(RD),
Robert
Forrest
(RD),
Jeanie
McAndrews
(RD),
Steve
Schaible
(RD),
HarryCraven
(EFED),
Diana
Locke
(HED),
Michael
Doherty(
HED),
Melba
Morrow
(AD),
Tom
Brennan
(HED),
Mark
Perry
(SRRD),
and
Larry
Schnaubelt
(SRRD).
The
presenters
were:
Mark
Perry
and
Larry
Schnaubelt
(SRRD).
The
Executive
Secretaries
for
the
meeting
were
Jeanie
McAndrews
and
Steve
Schaible
(RD).
Also
in
attendance
at
the
meeting
were
Marianne
Lewis,
Judy
Loranger,
and
Ben
Gregg,
all
of
SRRD.

At
this
meeting,
the
available
information
on
twenty­
five
different
plant
and
animal
byproduct
substances
was
discussed
to
determine
if
sufficient
information
was
available
to
make
tolerance
reassessment
decisions
on
the
various
materials
and
to
make
the
determination
as
to
whether
the
various
materials
should
be
classified
as
List
4A
or
List
4B
substances.
The
25
substances
discussed
do
not
represent
the
universe
of
plant
and
animal
byproduct
inert
ingredients,
but
instead
are
a
subset
which
have
existing
tolerance
exemptions
listed
in
40
CFR
Part
180
and
can
therefore
be
counted
towards
tolerance
reassessment.
The
available
information
consisted
of
information
retrieved
from
various
websites
such
as
TOXNET,
FirstGov,
and
NTP,
as
specified
in
the
methodology
for
lower
toxicity
chemicals.
General
Internet
searches
on
the
substance
names
and
their
toxicity
were
also
used.

Information
handed
out
at
this
meeting
included:
(1)
a
short
summary
dividing
the
substances
into
25
groups
for
discussion
purposes;
(2)
an
animal
toxicity
data
summary
for
linseed
oil;
and
(3)
a
summary
of
developmental,
reproductive,
and
chronic
toxicity
studies
for
gum
arabic.
Page
3
of
15
For
purposes
of
evaluation
in
accordance
with
the
newly
developed
inert
ingredient
methodology,
manyinert
substances
undergoing
tolerance
or
tolerance
exemption
reassessment
have
been
placed
into
groups
based
on
possible
common
characteristics
or
potential
similarity
based
on
the
fact
that
they
are
derived
from
materials
that
may
generally
be
considered
similar
to
each
other.
The
term"
plant
and
animal
byproducts"
is
used
by
the
Agency
to
describe
a
group
of
chemical
substances
that
are
derived
fromplant
and
animal
sources.
Some
of
the
substances
in
this
group,
such
as
walnut
shells
or
coconut
shells,
are
only
minimally
processed
from
the
direct
plant
material.
This
is
usually
a
change
only
in
the
physical
formof
the
substance,
and
is
accomplished
by
activities
such
as
grinding
or
chopping.
Some,
however,
require
more
significant
processing
in
order
to
generate
the
endproduct
such
as
lecithin
from
oil,
or
glue
from
animal
collagen.
The
plant
and
animal
byproduct
substances
considered
by
the
IIFG
are
used
for
a
variety
of
purposes
as
inert
ingredients.
In
pesticide
products,
these
substances
are
used
as
surfactants,
thickeners,
carriers,
emulsifiers,
adhesive,
dispersing
agents,
and
many
other
uses.

Ecological
Effects:

The
substances
in
this
group
are
derived
fromnaturally
occurring
plant
and
animal
materials
and
no
adverse
ecological
effects
were
reported
in
the
available
literature.
However,
it
was
considered
that
three
compounds
(guar
gum,
sodiumalginate,
and
soap
bark,
which
act
as
a
foaming
agent,
foam
stabilizer,
and
stabilizer/
thickener,
respectively)
could
have
ecological
impacts.
After
consultation
with
OPPT
and
using
Structural
Activity
Relationships
(SARs),
the
IIFG
believes
that
these
compounds
are
of
low
concern
for
ecotoxicity.
The
IIFG
believes
that
no
significant
adverse
ecological
effects
are
anticipated
from
exposure
to
any
of
these
substances.

Discussion
Abrief
summation
of
the
available
information
was
given
for
each
of
the
chemical
substances.
If
available,
the
CAS
RegistryNumber
is
given
in
parenthesis.
Comments
made
during
the
discussion
or
after
the
meeting
that
pertained
only
to
a
specific
group
are
in
italics
below.
Current
List
classification
is
also
in
italics.

1.
Animal
Glue:

S
manufactured
from
collagen
derived
from
animal
hides
S
glue
may
be
slightly
allergenic
to
individuals
with
sensit
ivity
to
certain
proteins;
allergic
reactions
are
reversible.

Animal
glue
is
a
protein,
and
alien
proteins
may
cause
allergic
reactions.
However,
these
contact
(dermally­
induced)
reactions
are
reversible
and
are
generally
not
life
threatening.

2.
Coconut
Shells,
Douglas
Fir
Bark
(List
4A),
Walnut
Shells
(List
4A):

S
coconut
shells
used
to
make
activated
charcoal
(carbon)

S
Douglas
fir
bark
commonly
used
as
a
landscaping
mulch
Page
4
of
15
These
compounds
are
minimally
processed
from
their
natural
forms,
in
most
cases
being
only
ground
or
shredded
more
finely.
As
these
substances
are
in
effect
naturally
occurring,
it
is
not
expected
that
pesticidal
use
of
these
substances
will
result
in
adverse
exposure
to
humans
or
the
environment.

3.
Coffee
Grounds:
(CAS:
68916­
18­
7)
(List
4A)

As
the
extract
from
ground
coffee
beans
is
widely
consumed,
it
is
unlikely
that
use
of
coffee
grounds
as
an
inert
ingredient
in
a
pesticide
formulation
will
result
in
unacceptable
risk
to
humans.

3.
Licorice
Root:
(CAS:
68916­
18­
7)
(List
3­
"licorice
extract")

S
contains
glycyrrhizinic
acid
which
exhibits
actions
similar
to
natural
mineralocorticoids
of
the
adrenal
cortex
S
licorice
root
is
one
of
the
most
commonly
used
herbs
in
the
world;
licorice
extracts
are
used
as
a
food
additive
flavoring
agent
in
mouthwash,
root
beer,
chewing
gum,
candy,
ice
cream,
baked
goods,
and
as
a
pharmaceutical
additive
S
licorice
and
licorice
derivatives
are
on
FDA's
list
of
direct
food
substances
affirmed
as
generally
recognized
as
safe
(GRAS)
(21
CFR
184.1408);
maximumlevels
permitted
in
food
are
specified
S
according
to
ToxNet,
licorice
extract
is
characterized
as
being
"slightly
toxic"
by
the
oral
route;
toxicity
endpoints
are
as
follows:
LD50
rat
oral
=
14,200
mg/
kg,
LD50
rat
inter­
peritoneal
=
1420
mg/
kg,
LD50
rat
subcutaneous
=
4200
mg/
kg,
LD50
mouse
inter­
peritoneal
=
1500
mg/
kg.

S
cases
of
poisonings
are
mostly
chronic
in
nature,
not
acute;
chronic
exposure
longer
than
4­
6
weeks
may
cause
hypokalemia
(low
potassium
levels),
hypernatremia
(high
sodium
levels),
hypertension,
myopathy,
and
cardiac
problems
S
"licorice
extract"
(CAS:
97676­
23­
8)
is
classified
as
List
3;
this
CAS
Number
actually
refers
to
"oils,
licorice"

S
no
serious
adverse
reactions
have
been
published
about
licorice
root;
single
chemical
extracts
have
caused
serious
adverse
reactions
on
occasion
when
used
in
medicine
or
candy,
but
the
whole
root
does
not
cause
these
serious
reactions.

Exposure
to
licorice
root
from
use
as
an
inert
ingredient
in
pesticidal
products
will
be
well
below
those
levels
of
licorice
extract
already
considered
safe
by
other
federal
agencies.

4.
Sperm
Oil:
(CAS:
8002­
24­
2)

S
liquid
wax
derived
from
sperm
whale
blubber.

S
used
as
a
lubricant
for
watches
and
other
delicate
instruments,
in
leather
treatment
products
and
soap
making
S
sperm
oil
is
a
food
additive
permitted
for
direct
application
to
food
for
human
consumption
(21
CFR
172.210)
as
well
as
an
indirect
food
additive
in
adhesives,
paper
and
paperboard
components,
and
polymers
(21
CFR
Parts
175,
176,
and
177)
Page
5
of
15
Barring
incidence
data
on
adverse
effects
after
exposure
to
spermoil,
this
chemical
should
be
added
to
List
4A.
According
to
Jerome
Blondell
(HED)
and
Norman
Spurling,
there
are
no
records
for
sperm
oil
in
the
Incidence
Data
System
database.

5.
Wood
Flour
(Wood
Dust):.

S
according
to
health
and
safety
guidelines
put
out
by
the
Occupational
Safety
and
Health
Administration
(OSHA),
acute
exposure
to
red
cedar
dust
may
result
in
irritation
of
the
eyes,
skin
and
respiratory
tract.
Chronic
occupational
exposure
may
result
in
dermatitis
reactions,
asthma,
pneumonitis,
bronchitis
and
nasal
cancer.

S
it
is
believed
that
toxicity
is
dependant
on
wood
type,
with
nasal
cancer
and
more
severe
respiratory
effects
being
associated
with
exposure
to
dust
from
hardwoods
such
as
beech,
walnut,
and
oak
S
OSHA
permissible
exposure
limit
(PEL)
for
red
cedar
dust
is
15
mg/
m
3
for
total
dust,
and
5
mg/
m
3
for
respirable
fractions
(nuisance
dust)

S
National
Institute
of
Occupational
Safety
and
Health
(NIOSH)
recommended
exposure
limit
(REL)
is
1
mg/
m
3
(as
a
time­
weighted
average
(TWA)
for
up
to
10
hour
workday
and
a
40
hour
work
week),
based
on
pulmonary
dysfunction
and
other
respiratory
effects
Exposure
to
wood
dust
or
wood
flour
in
a
formulated
pesticide
product
is
likely
to
be
well
below
the
levels
which
result
in
chronic
effects
fromdaily
occupational
inhalation
exposure
to
rawwood
dust.

6.
Camphor:
(CAS:
76­
22­
2)
(List
3)

S
derived
from
the
camphor
tree,
Cinnamomum
camphora
S
Japanese
white
camphor
oil
(CAS:
8008­
51­
3)
and
d­
camphor
(CAS:
464­
49­
3)
permitted
as
a
food
additive
permitted
for
direct
addition
to
food
for
human
consumption
(21
CFR
172.510
and
172.515,
respectively)

S
reported
uses
include
as
an
ingredient
in
non­
alcoholic
beverages,
baked
goods,
condiments,
and
in
over­
the­
counter
medications
to
relieve
muscle
aches,
nasal
congestion
and
cold
sores;
also
used
in
the
manufacture
of
plastics,
lacquers/
varnishes,
pyrotechnics
and
embalming
fluid
S
currently
present
in
approximately
950
non­
pesticidal
products
S
ingredient
in
insecticides
and
moth
and
mildew
preventatives
S
OSHA
PEL:
TWA
2
mg/
m
3
S
NIOSH
REL:
TWA
2
mg/
m
3
S
tolerance
exemption
specifies
that
camphor
not
compose
more
than
5%
(w/
w)
of
pesticide
formulation.

Camphor
is
rapidly
absorbed
through
the
skin,
respiratory
and
GI
tracts.
Camphor
readily
crosses
the
placenta
and
cases
of
fetal
death
after
ingestion
by
mother
have
been
reported.
Ingestion
of
0.7
to
1.
0
g
has
proven
fatal
in
children.
Human
fatalities
have
also
been
reported
as
a
result
of
dermal
and
respiratory
exposure.
A
Poisindex
review
of
camphor
ingestions
(estimated
to
exceed
2
mg/
kg)
showed
that
90%
of
patients
remained
asymptomatic,
4%
developed
minor
symptoms
and
6%
developed
major
symptoms.
Humans
are
considered
more
susceptible
to
the
effects
of
camphor
than
other
species.
Camphor
is
irritating
to
skin,
upper
respiratory
tract,
and
the
gastrointestinal
Page
6
of
15
tract.
It
is
toxic
and
reacts
rapidly;
exposure
may
result
in
dizziness,
tension,
hallucinations
and
mental
confusion.
Chronic
camphor
poisoning
is
uncommon
due
to
its
high
toxicity
and
rapid
action.

A
developmental
toxicity
study
in
rabbits
(with
d­
camphor)
showed
no
fetal
or
maternal
toxicity
at
400
mg/
kg/
day,
yet
an
associated
range
finding
study
found
60%
maternal
mortalityat
500
mg/
kg/
day.
Another
developmental
toxicity
study
in
rats
(d­
camphor)
demonstrated
that
camphor
does
not
affect
fetal
growth,
viability
or
morphological
development
at
doses
which
caused
only
minor
maternal
toxicity
(800
mg/
kg/
day).

Camphor
will
be
further
evaluated
using
a
more
formal
(Tier
2)
assessment
process.

7.
Mixed
Phytosterols
(plant
sterols):

S
phytosterols
(e.
g.,
campesterol,
sitosterol,
and
stigmasterol)
are
ubiquitous
compounds
in
plant
s
similar
to
animal
sterols
but
having
an
extra
methyl
or
ethyl
substituent
in
the
side
chain;
plant
sterols
are
found
in
plant
cell
walls
and
in
plant
oils;
the
content
of
sterols
in
plant
oilsrange
fromhundredsofmg
per100
g
tolessthan10
mg
S
the
tolerance
exemption
expression
in
40
CFR180.1001(
d)
is
for
use
in
pesticide
products
of
"mixed
phytosterols
(consisting
of
campest
erol,
sitosterol,
and
stigmasterol,
with
minor
amounts
of
associated
plant
sterols)
derived
from
edible
vegetable
oils"
as
a
surfactant
S
most
information
describes
potential
benefits
derived
from
dietary
consumption­
mixed
phytosterols
and
phytosterol
esters
lower
total
blood
cholesterol
and
LDL­
C;
it
is
believed
that
phytosterols
interfere
with
dietary
and
endogenous
(biliary)
cholesterol
absorption
8.
Soapbark
(Quillaja
Saponin):
(CAS:
1393­
03­
9)
(List
3)

S
derived
from
soapbark
tree
S
contains
saponins
which
are
natural
detergents/
surfactants
that
have
been
used
to
make
soap
and
used
as
a
foaming
agent
in
certain
beverages
(like
root
beer)

S
permitted
as
a
food
additive
permitted
for
direct
addition
to
food
for
human
consumption
(21
CFR
172.510)

S
liquid
solutions
and
dusts
reported
to
cause
reversible
eye
irritation
and
respiratory
sensitization
S
no
adverse
effect
on
death
rate
or
incidence
of
histopathological
findings
(including
tumors)
were
observed
in
mice
(both
sexes)
fed
quillaja
extract
for
84
weeks;
at
high
dose
there
was
decreased
body
weight
gain
and
differences
in
hematological
examinations
and
in
some
absolute
and
relative
organ
weights
of
both
sexes
Soap
bark
may
be
associated
with
formulations
of
fire
retardants
which
may
have
ecological
impacts.
After
consultation
with
OPPT
and
using
Structural
Activity
Relationships
(SARs)
the
IIFG
believes
that
these
compounds
are
of
low
concern
for
ecotoxicity.
Therefore,
the
IIFG
believes
that
no
significant
adverse
ecological
effects
are
anticipated
from
exposure
to
soapbark.

9.
Wool
Fat
(anhydrous
lanolin):
(CAS:
8006­
54­
0)
(List
4A­
lanolin)

S
lanolin
is
a
greasy,
yellow
substance
extracted
fromsheep
wool;
a
mixture
of
cholesterol
and
Page
7
of
15
the
esters
of
several
fatty
acids
S
anhydrous
lanolin
refers
to
lanolin
which
contains
less
than
0.
25%
water
S
used
as
an
ointment
base
in
cosmetics
and
pharmaceuticals,
as
a
lubricant,
and
in
finishing
and
preserving
leather;
also
a
constituent
of
some
varnishes
and
paint
S
lanolin
is
regulated
by
FDAas
a
food
additive
permitted
for
direct
addition
to
food
for
human
consumption
(21
CFR
172.615),
as
well
as
an
indirect
food
additive
(21
CFR
Parts
175­
178)

S
dermal
sensitivity
to
lanolin
has
been
reported,
with
a
high
incidence
of
lanolin
allergy
amongst
eczema
patients;
ToxNet
reports
that
lanolin
should
not
be
used
in
ointments
intended
for
use
by
sensitive
individuals
S
lanolin
is
considered
practically
non­
toxic
by
the
oral
route,
according
to
ToxNet.

S
pesticidal
uses
of
lanolin
as
an
active
ingredient
were
canceled
in
1998
as
there
were
no
active
product
registrations
containing
the
substance
S
"lanolin"
(CAS:
8020­
84­
6)
is
classified
as
List
4A
The
focus
group
believes
that
this
substance
is
not
an
allergen,
but
that
there
was
individual
sensitivity
to
the
substance.

10.
Castor
oil:
(CAS:
8001­
79­
4)
(List
4B)

S
a
natural
oil
obtained
from
the
seed
of
the
castor
bean;
after
the
hulls
are
removed
the
seeds
are
cold
pressed
S
medicinal
castor
oil
is
prepared
from
the
yield
of
the
first
pressing;
this
is
used
as
a
purgative
and
laxative;
oil
from
the
second
pressing
is
used
as
a
lubricant
for
machinery,
as
a
softening
agent
in
making
artificial
leather,
in
the
dressing
of
genuine
leather,
in
brake
fluids,
and
in
paints
and
plastic
materials
S
FDA
direct
food
additive
permitted
in
food
for
human
consumption,
as
a
releasing
and
antisticking
agent,
not
to
exceed
500
ppmin
hard
candy
(21
CFR
172.876);
as
a
natural
flavoring
substance
or
substance
used
in
conjunction
with
flavors
(172.510);
and
as
an
indirect
food
additive
(numerous
citations
in
21
CFR
Parts
175­
178);
also
used
in
cosmetics
and
pharmaceuticals
S
EPA
FIFRA
25b
active
ingredient
S
Irritating
to
rabbit
skin;
slightly
toxic
by
oral
route.
Another
source
considers
castor
oil
to
be
"moderately
toxic"
by
ingestion.
Contraindicated
for
pregnant
women;
overdose
has
caused
stillbirth
and
kidney
damage.

As
referenced
on
National
Toxicology
Program's
(NTP)
web
site,
animal
feeding
studies
(up
to
10%
in
diet
for
13
wks.)
in
rats
and
mice
resulted
in
no
significant
adverse
effects.
Genotoxicity
studies
were
negative
for
mutation
induction
in
Salmonella
typhimurium,
for
induction
of
sister
chromatid
exchanges
and
for
induction
of
micro
nuclei
in
mice
peripheral
blood
erythrocytes.

Dietary
exposure
to
residues
of
castor
oil
from
pesticidal
use
as
an
inert
ingredient
will
not
approach
levels
regulated
by
FDA
as
a
direct
or
indirect
food
additive
or
ingredient
in
cosmetics.

11.
Hydrogenated
Castor
Oil:
(CAS:
8001­
78­
3)
(List
3)
Page
8
of
15
S
manufactured
by
hydrogenation
of
castor
oil
in
the
presence
of
nickel
catalyst
with
pressure
and
temperature;
a
hard,
brittle
wax
that
is
extremely
insoluble
and
is
well
suited
for
products
needing
resistance
to
water,
oils,
petroleum,
and
petroleum
derivatives
S
mainly
used
in
manufacturing
greases,
but
also
used
in
paper
coatings
for
food
packaging
The
tolerance
exemption
in
40
CFR
180.1036
for
hydrogenated
castor
oil
reads
as
follows:

"The
adhesive
hydrogenated
castor
oil
is
exempt
from
the
requirement
of
a
tolerance
for
residues
in
or
on
the
raw
agricultural
commodity
cottonseed
when
used
as
an
inert
adhesive
for
formulations
of
the
attractant
gossyplure
to
disrupt
the
mating
of
the
pink
bollworm."

12.
Boiled
Linseed
Oil:
(CAS:
8001­
26­
1)
(List
4A­
linseed
oil)

S
an
amber­
colored,
fatty
oil
extracted
from
the
cotyledons
and
inner
coats
of
the
linseed,
the
seed
of
the
flax
plant
(Linum
usitatissimum);
also
known
as
flaxseed
oil
S
raw
oil
is
pale
in
color
and
practically
odorless
and
t
asteless;
boiled
oil
is
darker
and
has
a
bitter
taste
and
unpleasant
odor
S
used
as
a
drying
agent
in
paints,
varnishes,
adhesives,
inks
and
resins
S
linseed
oil
(not
boiled)
is
an
EPA
FIFRA
25b
active
ingredient
S
linseed
oil
(not
boiled)
is
an
FDA
prior
sanctioned
food
ingredient;
"substances
classified
as
drying
oils,
when
migrating
fromfood­
packaging
material
(as
components
of
finished
resins)
shall
include...
linseed
oil"
(21
CFR
181.26)

S
according
to
ToxNet,
boiled
linseed
oil
should
not
be
taken
internally,
due
to
the
addition
of
lead
and
other
toxic
element;
the
boiled
oil
may
cause
skin,
eye
and
respiratory
tract
irritation
through
the
inhalation
route.
Consumption
of
boiled
linseed
oil
is
contraindicated
since
lead,
manganese
and/
or
cobalt
is
often
added
S
rats
fed
boiled
linseed
oil
during
lactation
and
gestation
had
most
offspring
die
within
3
days
of
birth:
6­
month
old
Wistar
rats
were
fed
boiled
linseed
oil
during
gestation
and
lactation
(compared
to
a
control
group
fed
fresh
linseed
oil
or
peanut
oil);
mortality
in
the
young
was
higher
than
normal,
it
was
assumed
cyclic
monomers
det
ect
ed
in
the
liver
fatty
acids
were
responsible
for
toxicity
in
the
boiled
oil
S
the
fresh
oil
does
not
have
the
toxicity
concerns
that
are
associated
with
the
boiled
oil
The
tolerance
exemption
in
40
CFR
180.1056
for
boiled
linseed
oil
reads
as
follows:

"Boiled
linseed
oil
(containing
no
more
than
0.33
percent
manganese
naphthenate
and
no
more
than
0.33
percent
cobalt
naphthenate)
is
exempt
from
the
requirement
of
a
tolerance
when
used
as
a
coating
agent
for
S
ethyl
hexahydro­
1H­
azepine­
1­
carbothioate.
No
more
than
15
percent
of
the
pesticide
formulation
may
consist
of
`boiled
linseed
oil.
'
This
exemption
is
limited
to
use
on
rice
before
edible
parts
form."

13.
Carrageenan:
(CAS:
9000­
07­
1)
(List
4A)

S
derived
from
red
algae
S
used
as
a
thickener/
stabilizer
in
foods
such
as
chocolate,
milk,
ice
cream,
pudding,
yogurt,
Page
9
of
15
frostings
and
cream
soups
S
FDA
direct
food
additive
(21
CFR
172.620)
and
a
substance
generally
recognized
as
safe
by
FDA
(21
CFR
182.7255)

S
natural
carrageenan,
which
has
a
molecular
weight
between
100,000
and
1,
000,000
can
be
chemically
altered
to
form
degraded
carrageenan;
degraded
carrageenan
has
a
molecular
weight
between
20,000
and
30,000,
and
has
demonstrated
significantly
higher
toxicity
in
animal
studies,
including
malignancies
in
the
gastrointestinal
tract;
degradation
may
occur
in
the
human
body
S
considered
to
be
a
"water
absorbing
polymer"

S
algin
gum
(CAS:
9049­
05­
2),
or
calcium
carrageenan,
is
included
on
List
3
Carrageenan
will
be
further
evaluated
using
a
more
formal
(Tier
2)
assessment
process.

14.
Dextrin:
(CAS:
9004­
53­
9)
(List
4A),
Corn
Dextrin
S
natural
polymer
used
clinically
as
a
peritoneal
dialysis
solution
and
as
a
controlled
drug
delivery
formulation;
also
used
in
distilleries,
breweries,
and
the
manufacture
of
cotton
goods,
rayon,
paper
products,
adhesives,
explosives
and
steel
S
acute
toxicity
includes
skin
irritation,
as
well
as
inhalation
and
ingestion
hazard
(large
amounts
may
cause
gastro­
intestinal
upset).
Another
source
reported
no
adverse
health
effects
expected
from
inhalation
or
skin
contact­
however,
dust
may
cause
eye
irritation
(mechanical).
Negative
in
a
series
of
10
mutagenicity
studies
(1992)
which
tested
"indigestible
dextrin".

S
direct
food
additive
affirmed
as
GRAS
(21
CFR
184.1277)

15.
Furcelleran:
(CAS:
9000­
21­
9)

S
extracted
fromFurcellaria
fastigiata
(red
seaweed)
and
used
as
an
emulsifier,
stabilizer,
and
thickener
in
foods
S
FDA
direct
food
additive
(21
CFR
172.655)

S
a
potential
"water
absorbing
polymer"

Furcelleran
will
be
further
evaluated
using
a
more
formal
(Tier
2)
assessment
process
due
to
its
relationship
to
carrageenan.

16.
Guar
Gum:
(CAS:
9000­
30­
0)
(List
4A)

S
used
as
a
surfactant
and
related
adjuvant
of
surfactant;
also
used
as
a
stabilizer/
thickener
in
foods,
as
a
binding
and
disintegrating
agent
in
tablets,
and
in
suspensions,
emulsions,
lotions,
creams,
and
toothpaste
S
a
direct
food
additive
affirmed
as
GRAS
by
FDA,
with
maximum
permitted
usage
levels
in
foods
(21
CFR
184.1339)

S
acute
toxicity:
LD
50
(oral)
rat
­
6770
mg/
kg,
mouse
­
8100
mg/
kg,
rabbit
­
7000
mg/
kg,
hamster
­
6000
mg/
kg
S
guar
dust
may
cause
respiratory
tract
irritation
and
sensitization;
and
that
some
individuals
may
develop
a
respiratory
allergic
response,
or
persons
with
a
history
of
respiratory
allergies
Page
10
of
15
may
have
those
conditions
aggravated,
by
exposure
to
guar
dust.
Negative
in
a
series
of
15
mutagenicity
studies
(1992),
as
well
as
four
1982
studies,
and
one
pre­
1980
study.
Negative
in
rat
(F344)
and
mouse
(B6C3F1
)
in
a
National
Cancer
Institute
(NCI)
carcinogenesis
bioassay
S
considered
to
be
a
"water
absorbing
polymer"

S
FDAhas
reportedly
banned
the
use
of
guar
gumas
an
active
ingredient
in
drugs.
Because
this
complex
carbohydrate
swells
when
wet
it
had
been
used
in
weight­
loss
products
to
produce
a
feeling
of
fullness.
One
brand
resulted
in
hospitalization
of
10
patients
and
one
death
from
a
blood
clot
after
surgery
to
remove
a
throat
blockage.
Guar
gum
can
cause
diarrhea,
vomiting,
bloating,
and
intestinal
blockages.

17.
Gum
Arabic
(Acacia):
(CAS:
9000­
01­
5)
(List
4A)

S
A
neutral,
or
slightly
acidic,
salt
of
a
complex
polysaccharide;
derived
from
acacia
tree
sap
S
used
in
pharmaceuticals,
adhesives,
inks,
textile
printing,
cosmetics,
and
as
a
thickening
agent
and
colloidal
in
stabilizer
in
confectionary
and
food
products;
also
used
extensively
in
flavor
emulsions
S
a
direct
food
additive
affirmed
as
GRAS
by
FDA
(21
CFR
184.1330)

S
gum
arabic
is
considered
to
have
low
oral
toxicity
with
LD50
values
reported
as
follows:
oral
­
>16
g/
kg
­
rat;
>16
g/
kg
­
mouse;
8
g/
kg
­
rabbit;
and
>
18
g/
kg
­
hamster.
Estimates
of
the
probable
oral
lethal
dose
for
humans
are
>
15,000
mg/
kg
S
gum
arabic
has
been
shown
to
be
a
severe
allergen
in
the
workplace
and
has
led
to
skin
lesions
and
sever
asthmatic
attacks
in
humans
upon
exposure
to
the
dust
S
a
1971
study
of
37
German
printing
workers
exposed
to
gum
arabic
mist
reported
allergic
reactions
["
Printer's
Asthma"],
as
well
as
well­
defined
radiological
findings
in
the
lungs,
with
occasional
chronic
bronchitis
and
pulmonary
congestion;
hypersensitivity
reactions
upon
dermal
exposure
to
the
dust
have
also
been
observed
S
two
MSDS's
reported
eye
irritation,
one
as
severe
with
redness
and
pain
S
a
potential
"water
absorbing
polymer"

In
a
subchronic
13­
week
oral
mouse
study
no
compound­
related
effects
were
observed.
In
a
13­
week
oral
rat
study
no
compound­
related
effects
were
observed
except
for
a
reduction
in
feed
consumption
at
the
two
highest
dose
in
males
and
all
doses
in
females,
as
compared
with
the
control
animals.
The
author
reported
NOAELs
of
5,
200
mg/
kg/
day
and
13,800
mg/
kg/
day,
respectively,
for
male
and
female
rats.
The
date
of
this
study
was
reported
as
1982.

In
an
NTP
cancer
study,
there
were
no
statistically
significant
differences
obtained
from
oral
administration
of
gumarabic
when
control
rates
were
compared
to
those
observed
in
treated
groups.

The
IIFG
believes
that
while
there
are
no
concerns
for
exposure
via
the
oral
route,
there
could
be
a
contact
or
a
mist
problem
for
occupational
exposure,
based
on
the
presented
information.

18.
Lecithin:
(CAS:
8002­
43­
5)
(List
4A)

S
a
naturally
occurring
mixture
of
the
phosphatides
of
choline,
ethanolamine,
and
inositol;
Page
11
of
15
isolated
as
a
gum
following
hydration
of
solvent
extracted
soy,
safflower,
or
corn
oils.

S
widely
used
in
food
and
industrial
applications;
affirmed
by
FDA
as
GRAS,
and
used
in
foods
with
no
limitations
other
than
current
good
manufacturing
practice
(21
CFR
184.1400)

S
in
many
products,
lecithin
is
derived
from
soybean
S
acute
toxicity:
may
cause
transient
eye
irritation.
Also,
a
2­
day
study
of
mice
exposed
to
aerosolized
lecithin
reported
lungs
showing
focal
endothelial
cell
swelling
and
interstitial
edema
Many
products
containing
lecithin
are
derived
from
soy.
While
soybeans
are
considered
to
be
allergens,
the
information
available
to
the
Agency
indicates
that
the
allergen
invoking
compound
is
not
carried
over
in
the
extraction
process
that
produces
highly
refined
soybean
oil.
Therefore
there
are
no
allergen
concerns
associated
with
lecithin
even
though
it
is
processed
from
soybeans.
Studies
support
that
most
soy­
allergic
individuals
can
safely
eat
products
containing
soy
lecithin
without
experiencing
any
allergic
reaction.

Tolerance
reassessment
and
list
classification
decisions
will
also
apply
to
"lecithins,
soya"
(CAS:
8030­
76­
0).

19.
Sodium
Alginate:
(CAS:
9005­
38­
3)

S
the
sodiumsalt
of
alginic
acid;
produced
from
brown
algae
(Phaeophyceae)
by
processing
to
form
alginic
acid,
then
reacted
with
sodium
hydroxide
S
a
combustible,
colorless
or
yellowish
granular
or
powdery
solid;
insoluble
in
alcohol
and
ether;
forms
a
viscous
colloid
in
water
S
affirmed
as
GRAS
by
FDA,
with
maximum
permitted
usage
levels
in
foods
(21
CFR
184.1724)

S
used
as
a
foamstabilizer
in
brewing,
a
thickener
and
suspending
agent
in
soft
drinks,
a
binding
agent
in
pharmaceutical
tablets,
and
as
a
stabilizer
in
numerous
food
items
S
other
than
minor
irritation
of
eyes
and
skin
in
some
individuals,
no
other
health
effects
are
known
to
exist
S
according
to
ToxNet,
practically
non­
toxic
S
considered
to
be
a
"water
absorbing
polymer"

20.
Xanthan
Gum:
(CAS:
11138­
66­
2)
(List
4A)

S
a
water
soluble,
polysaccharide
gum
derived
from
Xanthomonas
campestris;
molecular
weight
between
five
and
ten
million
S
used
in
salad
dressings
and
other
products,
and
as
a
carrier
for
controlled
release
drugs
S
FDA
direct
food
additive
(21
CFR
172.695)

S
a
probable
"water
absorbing
polymer",
based
on
similar
properties
to
the
other
gums
in
this
group
21.
Locust
Bean
Gum:
(CAS:
9000­
40­
2)
(List
4B)

S
also
known
as
carob
gum;
derived
from
the
carob
seed
S
affirmed
GRAS
by
FDA
(21
CFR
184.1343)
Page
12
of
15
S
used
as
a
stabilizer,
thickener,
and
binder
in
foods
and
cosmetics;
a
pharmaceutic
agent;
and
in
paints,
textiles
and
paper
manufacturing
S
acute
oral
LD50
values
were
reported
as
follows:
13
gm/
kg
in
rats
and
mice;
9100
mg/
kg
in
rabbits;
and
10
gm/
kg
in
hamsters.
When
heated
to
decomposition
this
compound
emits
acrid
smoke
and
fumes.
Reported
negative
for
both
sexes
of
rats
and
mice
in
a
NTP
Carcinogenesis
Bioassay.
No
further
toxicity/
hazard
information
was
reported.

S
considered
to
be
a
"water
absorbing
polymer"

Discussion
Tolerance
reassessment
decisions
for
camphor,
carrageenan,
and
furcelleran
have
been
deferred
until
these
substances
can
be
further
evaluated.
For
the
remaining
substances,
there
are
no
concerns
for
ecotoxicity,
or
for
most
dietary
or
dermal
human
exposures.
Tolerance
exemptions
can
be
reassessed
for
these
25
substances.

While
there
is
the
potential
for
adverse
effects
to
wood
flour
or
wood
dust
fromthe
inhalation
route,
individuals
are
not
likely
to
be
exposed
at
the
levels
described
by
OSHA
from
pesticidal
application
of
products
containing
wood
dust
or
wood
flour
as
an
inert
ingredient.
OSHA
PELs
reflect
full
time
jobs,
that
may
lead
to
daily
exposures
(often
indoors)
over
the
course
of
many
years;
it
is
likely
that
these
worker
activities
will
create
the
possibility
of
respirable
sized
particles
as
a
result
of
routine
operations.
By
contrast,
mixing/
loading
and
applying
granular
or
dust
pesticide
products
that
have
these
same
wood
dust
will
not
have
the
same
level
or
types
of
exposures.
The
first
major
difference
is
the
time
and
duration
of
exposure.
For
most
cases
the
applicators
will
not
be
exposed
on
a
daily
basis.
In
fact,
it
is
much
more
likely
that
pesticide
handlers,
both
professional
and
homeowners,
will
only
have
short­
term
exposures
(from
1day/
month
to
1day/
year).
Additionally,
the
exposure
to
the
substance
as
an
inert
ingredient
is
likely
to
be
significantly
less
than
levels
experienced
through
occupational
exposure.

Several
of
the
plant
products
used
as
thickeners
have
been
identified
as
being
water
absorbing
polymers.
This
termrefers
to
substances
which
are
able
to
absorb
their
weight
in
water,
such
as
guar
gum,
sodiumalginate,
and
locust
bean
gum.
Other
related
substances
such
as
xanthan
gum
and
gum
arabic
are
also
likely
to
have
this
property
based
on
similar
characteristics.
These
chemicals
have
been
identified
as
posing
moderate
concern
for
human
health
through
the
inhalation
route
if
the
particle
size
is
sufficiently
small
to
be
inhaled
into
deep
lungs
(<
10
microns),
and
if
the
substance
is
sufficiently
present
in
the
formulation.
However,
in
their
use
as
thickeners
in
pesticide
formulations,
they
will
have
already
absorbed
water
and
"swelled"
to
a
larger
particle
size,
and
will
therefore
not
be
of
toxicological
concern
through
an
inhalation
route.

The
CAS
Registry
Number
on
List
3
for
"licorice
extract"
is
97676­
23­
8.
The
CAS
Number
for
"licorice
extract"
referenced
in
both
ToxNet
and
by
FDA
is
68916­
18­
7.
Using
the
National
Institutes
of
Health,
National
Library
of
Medicine's,
ChemIDplus
Locator
webpage,
the
CAS
Number
97676­
23­
8
refers
to
the
term"
licorice
oils"
and
the
proper
CAS
Number
for
licorice
extract
Page
13
of
15
is
68916­
18­
7.
Confusion
around
these
terms
will
be
cleared
up
by
expanding
the
List
classification
term
to
include
licorice
and
its
derivatives.

Currently,
boiled
linseed
oil
is
not
included
on
any
of
the
inert
ingredient
Lists,
but
has
specific
tolerance
exemption
language
included
in
180.1056;
"linseed
oil"
(presumably
unboiled)
is
included
in
List
4A.
It
appears
that
the
CAS
number
is
the
same
regardless
of
whether
the
substance
is
boiled
or
unboiled.

IIFG
Determinations
By
consensus
there
were
no
objections
to
the
following:

All
existing
tolerance
exemptions
for
the
plant
and
animal
byproduct
substances
listed
below
can
be
reassessed.
In
40
CFR180.1001(
c):
animal
glue;
coconut
shells;
coffee
grounds;
corn
dextrin;
dextrin;
guar
gum;
gum
arabic
(acacia);
lecithin;
licorice
root;
sodium
alginate;
sperm
oil;
walnut
shells;
wood
flour;
and
xanthan
gum.
In
40
CFR
180.1001(
d):
Douglas
fir
bark,
ground;
locust
bean
gum;
mixed
phytosterols
(consisting
of
campesterol,
sitosterol,
and
stigmasterol,
with
minor
amounts
of
plant
sterols)
derived
from
edible
vegetable
oils;
soapbark
(quillaja);
and
wool
fat
(anhydrous
lanolin).
In
180.1001(
e):
castor
oil,
U.
S.
P.;
dextrin;
sodiumalginate;
and
xanthan
gum.
In
180.1036
and
180.1056,
hydrogenated
castor
oil
and
boiled
linseed
oil,
respectively.

Terms
to
be
expanded
or
consolidated
as
part
of
the
tolerance
reassessment
decision
are
as
follows:

1.
"Wool
fat
(anhydrous
lanolin)"
in
180.1001(
d)
shall
become
"lanolin
(including
anhydrous
lanolin)"

2.
"Dextrin"
and
"corn
dextrin"
in
180.1001(
c)
(both
terms)
and
180.1001(
e)
(dextrin
only)
will
be
combined
into
the
term
"dextrin
(including
corn
dextrin)"
and
listed
in
both
paragraphs.

3.
The
tolerance
reassessment
decision
for
"lecithin"
will
also
apply
to
"lecithins,
soya"
and
a
tolerance
exemption
for
this
substance
can
be
established.

By
consensus
the
following
List
classifications
have
been
determined:

1.
Animal
glue:
Add
to
List
4A;
contact
allergenic
reactions
are
likely
to
be
reversible
and
the
exposure
levels
and
durations
likely
fromuse
as
an
inert
ingredient
in
pesticidal
formulations
do
not
justify
classifying
this
substance
as
List
4B.

2.
Coconut
shells,
walnut
shells,
and
Douglas
fir
bark:
List
4A
based
on
the
fact
that
these
substances
are
naturally
occurring
and
processing
fromtheir
natural
formis
minimal
for
their
use
as
inert
ingredients.
Page
14
of
15
3.
Coffee
grounds:
List
4A,
no
concern
expected
to
humans
or
the
environment.

4.
Licorice
root:
Reclassify
"licorice
extract"
from
List
3
to
List
4B,
and
change
the
List
classification
term
to
"Licorice
and
licorice
derivatives"
such
that
licorice
root,
licorice
oils,
and
licorice
extract
are
all
reflected.
CAS
numbers
for
both
licorice
extract
and
licorice
oils
should
be
listed.
Licorice
is
widely
used
in
foods
and
pharmaceuticals;
toxicity
data
for
licorice
extract
suggests
some
chronic
effects
at
high
doses
(doses
not
likelyto
be
experienced
through
inert
ingredient
use
in
pesticide
formulations).

5.
Spermoil:
Classify
as
List
4A;
derived
from
whale
blubber,
no
incidence
data
exist
in
OPP's
Incident
Data
System
database
for
this
substance.

6.
Wood
flour:
Classify
as
List
4A;
literature
suggests
potential
chronic
exposure
concerns
for
wood
dust
frominhalation
route
in
occupational
setting.
These
exposure
durations
and
levels
will
not
be
realized
from
use
of
wood
dust
in
a
pesticide
formulated
product.

7.
Mixed
phytosterols:
Classify
as
List
4A
based
on
the
fact
that
no
concerns
were
identified.

8.
Soapbark
(Quillaja
Saponin):
Reclassify
from
List
3
to
List
4A;
based
on
SAR,
low
concern
for
ecotoxicity,
no
concerns
for
human
health.

9.
Wool
fat
(anhydrous
lanolin):
Currently
the
term
"lanolin"
is
included
on
List
4A­
it
should
remain
on
list
4A
but
the
term
should
be
expanded
to
"lanolin
(including
anhydrous
lanolin)"
and
list
both
CAS
numbers.
There
is
no
toxicologically
significant
difference
between
the
two
substances.

10.
Castor
oil:
Reclassify
from
List
4B
to
List
4A.

11.
Hydrogenated
castor
oil:
Reclassify
from
List
3
to
List
4B.

12.
Boiled
linseed
oil:
"Linseed
oil,
boiled"
should
be
classified
as
List
4B.
The
existing
"linseed
oil"
term
in
List
4A
should
remain
on
List
4A
but
be
changed
to
specify
"unboiled".

13.
Dextrin
and
corn
dextrin:
Currently
only
dextrin
in
included
in
List
4A.
Both
should
be
reflected
on
List
4A
under
the
term
"dextrin
(including
corn
dextrin)".

14.
Guar
gum:
Keep
on
List
4A.

15.
Gumarabic
(Acacia):
Reclassify
fromList
4Ato
List
4B,
based
on
contact
exposure
concerns
and
occupational
concerns
with
gum
arabic
mist.

16.
Lecithin:
Keep
at
List
4A;
the
pesticidal
use
of
this
substance
is
not
expected
to
result
in
exposures
near
that
from
existing
use
of
lecithin
as
a
dietary
supplement.
"Lecithins,
soya"
Page
15
of
15
(CAS:
8030­
76­
0)
should
be
added
to
List
4A.

17.
Sodium
Alginate:
Add
to
List
4A;
while
this
substance
may
be
applied
to
water
through
use
in
fire
retardant
products,
SARanalysis
suggests
that
no
significant
adverse
ecological
effects
are
anticipated
from
exposure
to
this
substance.

18.
Xanthan
gum:
Keep
on
List
4A.

19.
Locust
Bean
Gum:
This
substance
is
currently
on
List
4B,
yet
is
added
to
all
types
of
food.
The
group
recommended
that
this
compound
be
moved
to
List
4A.