Document ID: EPA-HQ-OPP-2004-0147-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-06-18T04:00Z

Zinc
Pyrithione
Summary
May
12,
2004
USES
Zinc
Pyrithione
(
also
known
as
Zinc
Omadine
®
or
Zinc
2­
pyridinethiol­
1­
oxide)
is
a
materials
preservative
used
to
prevent
microbial
degradation
and
deterioration
in
a
wide
variety
of
food/
drinking
water
contact,
and
non­
food
contact
finished
manufactured
articles
(
treated
articles),
and
in
their
precursor
materials.
It
is
considered
to
have
bacteriostat,
fungistat,
mildewstat,
and
algaestat
properties.
It
is
conditionally
registered
until
6/
30/
05
for
antifoulant
boat
paints
to
control
the
growth
of
slime,
algae,
and
marine
fouling
organism
(
e.
g.,
barnacles,
tubeworms,
etc.)
below
the
water
line
on
recreational
and
commercial
boat
hulls
in
fresh,
salt,
or
brackish
water.
It
is
also
used
to
control
bacterial
and
fungal
growth
on
laundered
products
in
industrial
settings.

The
largest
use
for
zinc
pyrithione
is
non­
pesticidal
(
i.
e.,
control
of
dandruff,
seborrheic
dermatitis,
and
psoriasis),
and
is
regulated
by
FDA.
It
is
the
active
ingredient
in
many
antidandruff
shampoos.

FORMULATIONS
Zinc
pyrithione
is
added
as
a
liquid,
powder
or
aqueous
dispersion
during
the
manufacturing
process
of
treated
articles
and
their
precursor
materials.
Zinc
pyrithione
is
added
usually
by
metering
pump
if
it
is
a
liquid,
and
by
open
pouring
if
it
is
the
powder
form.
It
is
added
at
a
point
where
thorough
mixing
will
take
place.

PRODUCTION
Total
U.
S.
zinc
pyrithione
annual
production
in
2003
for
pesticidal
purposes
was
about
241,000
pounds,
calculated
as
pure
active
ingredient.
Use
of
zinc
pyrithione
for
nonpesticidal
FDA
regulated
applications
accounted
for
the
vast
majority
of
total
chemical
production.

HEALTH
EFFECTS
Zinc
pyrithione
is
moderately
toxic
via
acute
oral
exposure
(
LD50
is
267
mg/
kg;
Toxicity
Category
II),
and
of
low
toxicity
by
the
dermal
route
(
LD50
>
2000
mg/
kg;
Toxicity
Category
III)
and
inhalation
route
of
exposure
(>
0.61
mg/
L;
Toxicity
Category
III).
Zinc
pyrithione
is
a
severe
eye
irritant
(
Toxicity
category
I)
but
does
not
appear
to
demonstrate
significant
dermal
irritation
(
Toxicity
category
IV),
and
is
not
a
dermal
sensitizer.

Repeated
dose
(
13
weeks)
toxicity
studies
indicate
that
by
the
dermal
route,
zinc
pyrithione
is
relatively
non­
toxic
(
decreased
food
consumption,
decreased
body
weight
gain,
decreased
food
efficiency
at
the
limit
dose
of
1000
mg/
kg/
day).
The
oral
route
toxicity
is
significantly
greater
(
increased
relative
organ
weights,
clinical
toxicity,
and
hindlimb
weakness
at
3.75
mg/
kg/
day).

Page
1
of
5
Page
2
of
5
In
both
oral
developmental
studies
in
rats
and
rabbits,
there
was
no
quantitative
evidence
of
increased
susceptibility
[
i.
e.,
maternal
and
developmental
no­
observed­
adverse
effect
levels
(
NOAELs)
were
the
same].
There
was
however,
qualitative
evidence
of
increased
susceptibility
(
i.
e.,
fetal
effects
such
as
skeletal
effects,
and
a
decreased
number
of
viable
fetuses
were
considered
to
be
more
severe
in
the
presence
of
minimal
maternal
toxicity).

Significant
nervous
system
deficits
following
either
acute
or
subchronic
oral
administration
are
observed
with
zinc
pyrithione,
including
cholinergic
effects,
hindlimb
weakness,
and
peripheral
neuropathy
in
the
form
of
axonal
degeneration.
Neurotoxicity
studies
are
thus
triggered
`
for
cause'
in
order
to
properly
characterize
the
effects
of
zinc
pyrithione
on
nervous
system
structure
and
function
as
well
as
a
more
adequate
identification
of
the
neurotoxic
dose­
response
in
adults.

RISKS
Food
Risk
 
The
acute
and
chronic
dietary
risk
from
food
alone
does
not
exceed
the
Agency's
level
of
concern
for
all
populations.

Drinking
Water
Risk
 
The
acute
and
chronic
dietary
risk
from
drinking
water
alone
does
not
exceed
the
Agency's
level
of
concern.

Residential
(
Non­
Occupational)
Risk
 
Residential
post­
application
exposures
show
that
short­,
intermediate­,
and
long­
term
dermal
risks
do
not
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOEs
>
300.
The
MOEs
are
greater
than
300
for
adult/
child
contact
with
zinc
pyrithione­
treated
rubber/
plastic
articles,
and
short­
and
intermediate­
term
incidental
oral
exposure
scenarios
for
infants/
children
that
could
contact
zinc
pyrithione­
treated
toys
via
toy­
to­
mouth,
and
hand­
to­
mouth
exposures.

The
following
residential
handler
exposure
scenarios
for
application
of
paints
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOE's
<
300),
and
are
therefore,
are
of
concern.

°
Residential
handlers
that
paint
using
an
airless
sprayer:
antifoulant
paint
use:
dermal
MOE
=
100
for
large
boats;
inhalation
MOEs
=
6­
33
material
preservative
use
in
paints:
dermal
MOE
=
118;
inhalation
MOE
=
15
°
Residential
handlers
that
paint
using
a
brush:
antifoulant
paint
use
for
all
boat
sizes:
dermal
MOE
=
22­
120;
inhalation
MOE
=
5­
140.

°
Residential
handlers
that
paint
using
an
aerosol
spray
can
(
inhalation
MOE
=
271).
Page
3
of
5
The
majority
of
the
painting
exposure
is
attributed
to
the
hands,
and
most
of
the
dermal
MOEs
would
not
be
of
concern
if
painters
wore
chemical
resistant
gloves.
However,
it
is
not
current
Agency
policy
to
assume
personal
protective
equipment
(
PPE)
for
residential
handlers.
Requiring
the
general
public
to
wear
gloves
and
respirators
during
application
of
paints
is
neither
feasible,
nor
enforceable.

Aggregate
Risk
 
Aggregate
risk
assessment
for
food,
water,
and
residential
exposures
were
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
several
months
to
lifetime)
exposures.
Dermal
and
oral
exposures
were
not
combined
in
the
aggregate
assessment
because
of
different
toxicological
endpoints.
Short­
and
intermediate­
term
aggregate
risks
are
considered
together
because
the
same
exposure
data
are
used
for
short
and
intermediate­
term
exposures,
and
the
endpoint
of
concern
is
the
same
for
short
as
for
intermediate­
term
non­
dietary
exposures.

The
acute
aggregate
risk
from
indirect
food
contact
and
drinking
water
do
not
exceed
the
Agency's
level
of
concern
for
adults
or
children.

The
short­
and
intermediate­
term
oral
aggregate
risks
for
dietary,
residential
(
incidental
oral)
and
drinking
water
exposure
do
not
exceed
the
Agency's
level
of
concern
for
adult
males
and
females
and
infants/
children.

Dermal
short­
and
intermediate­
term
aggregate
MOEs
for
an
adult
resident
that
could
simultaneously
contact
shoe
liners,
paint
containing
zinc
pyrithione
(
as
a
material
preservative)
via
an
aerosol
can
and
anti­
dandruff
shampoo
do
not
exceed
the
Agency's
level
of
concern.
Dermal
exposures
that
already
exceed
the
Agency's
level
of
concern
were
not
included
in
the
dermal
aggregate
risk
estimates
(
i.
e.,
antifoulant
paint
use,
and
some
materials
preservative
paint
use).

For
residential
paint
applications
using
a
paintbrush,
the
dermal
aggregate
MOEs
are
slightly
less
than
the
target
MOE
of
300
(
270)
and
exceed
the
Agency's
level
of
concern.

The
only
uses
which
pose
inhalation
exposure
are
from
the
residential
handler
applications
of
paint,
which
have
MOEs
that
exceed
the
Agency's
level
of
concern.
These
inhalation
MOEs
range
from
5­
140
for
antifoulant
paint
use,
and
15­
271
for
paint
containing
zinc
pyrithione
as
a
materials
preservative.
However,
these
risk
estimates
are
conservative
because
they
are
based
on
a
whole­
body
rat
90­
day
inhalation
study.

Occupational
(
Worker)
Risks
 
For
mixing/
loading
liquids
and
powders
in
closed
systems
(
i.
e.,
using
a
metered
pump,
or
automatic­
dispensing
techniques),
the
margin
of
exposure
(
MOE)
calculations
indicate
risks
(
i.
e.,
target
MOEs

100)
that
do
not
exceed
the
Agency's
level
of
concern
for
the
dermal
and
inhalation
exposure
scenarios
assessed.
Page
4
of
5
The
dermal
exposure
risks
do
not
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOE

100)
for
potential
short­
term,
intermediate­
term,
and
long­
term
exposures
during
open
mixing/
loading
of
powders
and
liquids,
for
all
the
scenarios
assessed.
Also,
the
dermal
and
inhalation
MOEs
for
the
laundered
fabrics
scenarios
were
not
of
concern.

However,
the
following
short­,
intermediate­,
and
long­
term
exposure
scenarios
have
inhalation
MOEs
which
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOEs
<
100).
Mitigation
measures
which
can
be
used
to
help
reduce
potential
inhalation
exposure
(
e.
g.,
appropriate
PPE,
closed
delivery
systems,
etc.)
will
be
discussed
and
resolved
with
the
registrants.


Mixing/
loading/
applying
powders
and
liquids
for
general
preservative
use
patterns
using
open
pour
methods
(
inhalation
MOE
=
50
for
liquid
formulations;
inhalation
MOE
=
15
for
powder
formulation);


Mixing/
loading/
applying
powders
and
liquids
for
paint
preservation
using
open
pour
methods
(
inhalation
MOE
=
50
for
liquid
formulations;
inhalation
MOE
=
15
for
powder
formulation),
and

Handling
zinc
pyrithione­
containing
paint
products
(
as
a
material
preservative)
using
an
airless
sprayer
application
method
(
inhalation
MOEs
=
44
and
4.4
with
and
without
the
use
of
an
organic
vapor
respirator
as
PPE,
respectively,
and
dermal
MOE
=
74
without
the
use
of
gloves
as
PPE).

ECOLOGICAL
RISKS
Zinc
pyrithione
is
very
highly
toxic
on
an
acute
basis
to
freshwater
and
marine
fish
and
invertebrates,
as
well
as
to
aquatic
plant
species.
Laboratory
tests
show
adverse
chronic
impacts
on
freshwater
and
marine
invertebrate
reproduction
and
growth,
at
very
low
ppb
concentrations.
These
adverse
growth
and
reproductive
effects
also
indicate
that
zinc
pyrithione
may
be
a
potential
endocrine
disrupter.

There
may
be
short­
lived
water/
sediment
partitioning
that
could
produce
adverse
acute
toxicity
exposures
to
the
chemical
for
benthic,
sediment­
dwelling
aquatic
organisms.
However,
since
zinc
pyrithione
degrades
fairly
quickly
in
both
freshwater
and
saltwater
soils
and
sediments,
and
is
expected
to
have
low
surface
water
concentrations,
any
acute
exposures
are
expected
to
be
short­
lived.
It
is
not
expected
to
persist
for
long
periods
in
water
and
microbial
soils
and
sediments,
and
is
therefore
not
expected
to
produce
adverse
chronic
effects.
Page
5
of
5
HOW
THE
RISK
PICTURE
MAY
CHANGE
Changes
and
refinements
to
the
risk
assessment
may
occur
after
consideration
of
the
public
comments.
The
outstanding
confirmatory
ecological
and
worker
exposure
data
for
the
conditional
antifoulant
paint
use
may
trigger
additional
studies.
The
acute
and
subchronic
neurotoxicity
data
could
lead
to
additional
refinements
in
the
risk
assessment.