Document ID: EPA-HQ-OPP-2004-0147-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-06-18T04:00Z

Page
1
of
27
Overview
Of
The
Zinc
Pyrithione
Preliminary
Risk
Assessment,
June
2,
2004
Introduction
This
document
summarizes
EPA's
preliminary
human
health
and
ecological
risk
findings
and
conclusions
for
the
antimicrobial
pesticide
Zinc
Pyrithione
(
also
referred
to
in
these
assessments
as
Zinc
Omadine
®
or
Zinc
2­
pyridinethiol­
1­
oxide),
as
presented
fully
in
the
following
ten
documents:

1.
Zinc
Pyrithione
(
Zinc
Omadine
®
)
:
AD
Preliminary
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
(
RED)
Document,
Antimicrobials
Division,
D301376,
4/
21/
04,
Deborah
Smegal.

2.
Zinc
Pyrithione
(
Zinc
Omadine
®
)
­
Revised
Toxicology
Endpoint
Selection
Report
 
Revised
to
address
Registrant
Error
Comments,
Antimicrobials
Division,
4/
1/
04,
Timothy
F.
McMahon,
Ph.
D.,
Senior
Toxicologist.

3.
Zinc
Pyrithione
(
Zinc
Omadine
®
)
:
Toxicology
Science
Chapter
For
the
Reregistration
Eligibility
Decision
Document,
PC
Code
088002,
Case
3030,
Barcode:
D301369,
Antimicrobials
Division,
4/
1/
04,
Timothy
F.
McMahon,
Ph.
D.,
Senior
Toxicologist.

4.
Zinc
Pyrithione
(
Zinc
Omadine
®
)
:
Occupational
and
Residential
Exposure
Assessment
for
the
RED
Document.
Chemical
No.
088002.
Case
No.
2480.
DP
Barcode:
D301370,
Antimicrobials
Division
4/
20/
04,
Doreen
Aviado,
Biologist/
Deborah
Smegal,
Toxicologist/
Risk
Assessor.

5.
Residue
Chemistry
Science
Chapter
for
Zinc
2­
pyridinethiol­
1­
oxide,
Antimicrobials
Division
A.
Najm
Shamim,
Ph.
D.,
Chemist,
no
date.

6.
Environmental
Fate
Science
Chapter
on
Zinc
Pyrithione
(
Zinc
Omadine
®
)
For
Reregistration
Eligibility
Document
(
RED),
Antimicrobials
Division,
D301372,
4/
14/
04,
A.
Najm
Shamim,
Ph.
D.,
Chemist.

7.
Revised
Environmental
Modeling
for
Zinc
Omadine
(
Zinc
pyrithione)
Antimicrobials
Division,
D301373,
4/
22/
04,
Siroos
Mostaghimi,
Ph.
D.,
Senior
Scientist.

8.
Zinc
Pyrithione
Ecological
Hazard
and
Environmental
Risk
Characterization
Chapter
for
the
Reregistration
Eligibility
Decision
(
RED)
Document
(
D301371),
Antimicrobials
Division
4/
15/
04,
Kathryn
Montague,
M.
S.,
Biologist.
Page
2
of
27
9.
Zinc
Omadine
 
Report
of
the
Hazard
Identification
Assessment
Review
Committee,
3/
19/
99,
Tim
McMahon.

10.
Zinc
Omadine
 
Report
of
the
FQPA
Safety
Factor
Committee,
8/
7/
01,
Brenda
Tarplee.

The
purpose
of
this
overview
summary
is
to
assist
the
reader
by
identifying
the
key
features
and
findings
of
these
risk
assessments
and
conclusions
reached
in
the
assessments.
This
standard
overview
format
was
developed
in
response
to
comments
and
requests
from
the
public
which
indicated
that
prior
risk
assessments
for
other
chemicals
were
difficult
to
understand
and
too
lengthy,
and
that
it
was
not
easy
to
compare
the
assessments
for
different
chemicals
due
to
the
use
of
different
formats.

Risks
summarized
in
this
document
are
those
that
result
only
from
the
use
of
zinc
pyrithione.
The
Food
Quality
Protection
Act
requires
that
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".
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
Although
it
is
possible
that
zinc
pyrithione
may
express
toxicity
through
a
common
mechanism
with
other
compounds,
at
this
time,
the
Agency
does
not
have
sufficient
reliable
information
to
make
this
determination.
Consequently,
the
risks
summarized
herein
are
only
for
zinc
pyrithione.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
zinc
pyrithione,
aggregate
exposure
assessments
will
be
performed
on
each
chemical,
followed
by
a
cumulative
risk
assessment.

Once
the
risk
assessments
are
available
to
the
public,
there
will
be
an
opportunity
for
the
public
to
view
them
and
to
comment
on
them.
Public
comments
may
be
submitted
to
the
OPP
electronic
docket
at:
www.
epa.
gov/
edocket
under
the
docket
number
OPP­
2004­
0147.
Meetings
with
stakeholders
(
e.
g.,
registrants,
distributors,
etc.)
are
planned
to
discuss
the
identified
risks
and
to
solicit
input
on
risk
mitigation
strategies.
This
feedback
will
be
used
to
complete
the
Reregistration
Eligibility
Decision
(
RED)
document,
which
will
include
the
resultant
risk
management
decisions.
The
Agency
plans
to
conduct
a
closure
conference
call
with
interested
stakeholders
to
discuss
the
final
regulatory
decisions
presented
in
the
RED.

The
Agency
changed
the
reregistration
case
name
for
this
chemical
from
"
Omadine
Salts"
to
"
Zinc
Pyrithione"
to
accurately
reflect
the
sole
active
ingredient
in
this
case.
Previously,
the
Omadine
Salts
case
contained
two
active
ingredients
(
ie.,
Zinc
Omadine
and
tert­
Butylamine
2­
pyridinethiol­
1­
oxide).
The
rationale
for
changing
the
case
name
is
that:
Omadine
is
a
registered
trade
name
and
the
Agency
prefers
not
to
use
trade
names
as
titles
of
documents;
the
plural
"
Salts"
in
the
case
name
indicates
multiple
actives
but
there
is
only
one
chemical
being
considered
(
ie.,
zinc
pyrithione);
harmonize
the
case
name
with
the
sole
active
ingredient;
and
the
second
chemical
previously
listed
in
this
case
(
ie.,
tert­
Butylamine
2­
pyridinethiol­
1­
oxide;
PC
Page
3
of
27
code
088005)
has
no
active
registered
products,
and
is
no
longer
a
registered
active
ingredient.

Use
Profile
!
Antimicrobial:
Zinc
pyrithione
is
used
as
an
industrial
preservative
to
prevent
microbial
degradation
and
deterioration,
and
to
maintain
the
integrity
of
manufacturing
precursor
materials
and
finished
manufactured
articles.
It
is
considered
to
have
bacteriostat,
fungistat,
mildewstat,
and
algaestat
properties.

It
is
registered
for
the
following
indirect
food/
drinking
water
contact
applications:
Incorporation
into
food
packaging
adhesives,
incorporation
into
articles
made
from,
or
coated
with,
FDA
approved
food
contact
polymers
including
food
processing
equipment,
conveyor
belts,
utensils,
and
storage
containers.

It
is
registered
for
the
following
non­
food/
non­
drinking
water
contact
applications:
Dry
film
preservation
of
joint
compounds;
glazing
compounds;
wood
fillers;
flooring
adhesives;
caulks;
sealants;
grouts;
patching
compounds;
paints
and
coatings
for
residential,
architectural,
industrial
and
non­
marine
applications;
dry
wall;
gypsum;
pearlite;
plaster­
like
or
mineral
based
building
materials
used
in
the
manufacture
of
ceilings,
ceiling
tile,
walls,
and
partitions.

Control
of
mildew
and
bacteria
in
styrene
butadiene
rubber
and
thermoplastic
resin
used
in
the
manufacture
of
a
wide
variety
of
products
such
as
carpet
fibers;
carpet
backings;
rubber
or
rubber­
backed
bath
mats;
foam
underlay
for
carpets;
synthetic,
non­
leather
materials;
foam
stuffing
for
cushions
and
mattresses;
wire
and
cable
insulation;
vinyl,
linoleum,
tile
and
other
synthetic
floor
coverings;
wall
coverings;
plastic
furniture;
athletic
flooring
and
mats;
mattress
liners,
covers
or
ticking;
molding;
mats;
gaskets;
weather
stripping;
coated
fabrics
for
furniture
cushions,
boat
covers,
tents;
tarpaulins
and
awnings;
rubber
gloves
(
non­
surgical);
garbage
bags,
cans,
and
other
refuse
containers;
bathtub
appliques;
garden
hose;
pipe
(
non­
potable
water);
ductwork;
air
filters;
air
filtration
components
and
media
for
industrial,
hospital,
residential,
and
commercial
heating
and
cooling;
conveyor
belts;
shower
curtains;
sponge
or
fiber
mops;
household
use
sponges;
toilet
brush
receptacles;
toothbrush
receptacles
(
non­
bristle
contact);
scrub
brushes
(
nonmedical
sink
mats
and
drain
boards;
storage
containers;
soap
dish
holders;
towel
bars;
components
of
uppers
in
footwear.

In­
can
preservation
of
latex
emulsions,
clay,
pigment
and
guar
gum
slurries
used
in
the
manufacture
of
adhesives,
caulks,
patching
compounds,
sealants
and
grouts.

Control
of
mildew
and
other
fungal
growth
in
non­
food
contact
polymer
systems
to
include
incorporation
into
PVC,
polyolefins,
polystyrene,
nylon,
thermoplastic
elastomers,
and
acrylonitrile
butadiene
styrene
used
in
the
manufacture
of
plastic
screens
for
tents,
Page
4
of
27
decks,
porches,
floor
coverings,
vinyl
wall
coverings,
coated
fabrics,
swimming
pool
liners,
shower
curtains,
marine
upholstery,
tarpaulins,
roofing
membranes,
automotive,
pond
and
ditch
liners,
wire
and
cable,
plastisol
coatings
used
to
form
a
liquid
vinyl
material
to
coat
screens
or
mesh
materials
for
enclosures,
refrigerator
gaskets.

Control
of
bacterial
and
fungal
growth
on
laundered
products
in
industrial
settings
(
not
intended
for
residential,
commercial,
or
institutional
settings).

In
addition,
it
is
conditionally
registered
until
6/
30/
05
as
an
antifouling
agent
for
boat
paints
to
control
the
growth
of
slime,
algae,
and
marine
fouling
organism
such
as
barnacles
and
tubeworms
below
the
water
line
of
recreational
and
commercial
boat
hulls
in
fresh,
salt,
or
brackish
water.
This
use
is
conditionally
registered
pending
receipt
of
acceptable
confirmatory
data
listed
in
this
document's
"
Summary
of
Pending
Confirmatory
Data".

The
chemical
is
also
used
as
the
active
ingredient
of
anti­
dandruff
shampoos,
but
this
is
a
non­
pesticidal
use
regulated
by
FDA.

!
Formulations:
Powder,
liquid
or
aqueous
dispersion
for
incorporation
into
treated
articles
and/
or
their
precursor
materials,
and
into
ready­
to­
use
antifoulant
boat
bottom
paints.

!
Method
of
Application:
The
end
use
products
are
added
during
the
manufacturing
process
of
the
treated
articles
and
treated
article
precursor
materials.
Zinc
pyrithione
formulations
are
added
usually
by
metering
pump
if
they
are
liquids,
and
by
open
pouring
if
they
are
the
powder.
They
are
added
at
a
point
where
thorough
mixing
will
take
place.
The
antifoulant
paints
are
applied
by
brush,
roller,
and
by
spraying
(
airless).

!
Use
Rates:
The
dosages
below
are
based
on
using
the
product
containing
95%
active
ingredient
concentration.
End
use
products
with
lower
concentrations
of
active
ingredient
use
higher
product
application
rates
that
produce
the
same
concentration
of
active
ingredient.

Food
contact
clearances/
incorporation
rates
 
(
A)
On
July
18,
1995,
zinc
pyrithione
(
95%)
received
FDA
approval
for
use
in
preservation
of
food
packaging
adhesives,
at
a
maximum
use
concentration
of
1000
ppm,
at
use
temperatures
up
to
120
degrees
Fahrenheit,
and
subject
to
Good
Manufacturing
Practices,
including
the
conditions
specified
in
21
CFR
175.105
(
a)
and
(
b).

(
B)
On
December
16,
1994,
zinc
pyrithione
received
FDA
approval
for
incorporation
into
FDA
approved
polymers
listed
in
21
CFR,
Parts
174
through
186
(
inclusive),
or
in
the
FDA's
"
Food
Contact
Substance
Notification
System."
It
is
restricted
to
use
applications
at
or
below
room
temperature.
It
is
not
approved
for
the
incorporation
into
any
food
Page
5
of
27
N+
O
S
N+
S
O
Zn
2­
contact
substance
other
than
approved
and
listed
FDA
food
contact
polymers
at
750
to
1000
ppm
of
the
95%
product
(
0.75
to
1.0
lb)
per
1000
lbs
of
food
contact
polymer.

Non­
food
contact
incorporation
rates
Incorporation
rates
using
the
95%
zinc
pyrithione
article
product,
range
between
750
­
5000
ppm/
1000
pounds
of
material
to
be
treated
(
i.
e.,
0.75
B
5.0
lb/
1000
lb
material).
Incorporation
rates
using
the
5%
zinc
pyrithione
product,
range
between
10,000
­
44,000
ppm/
1000
pounds
of
material
to
be
treated
(
i.
e.,
10.0
B
44.4
lb/
1000
lb
material).

!
Annual
Poundage:
Total
zinc
pyrithione
production
for
pesticidal
purposes
(
including
antifoulants)
in
the
U.
S.
was
about
241,000
pounds
in
2003,
calculated
as
pure
active
ingredient.
Use
of
zinc
pyrithione
for
non­
pesticidal,
FDA
regulated
applications
(
i.
e.,
control
of
dandruff,
seborrheic
dermatitis,
and
psoriasis)
accounted
for
the
vast
majority
of
total
chemical
production
(>
million
pounds/
year).

!
Technical
Registrant:
Arch
Chemicals,
Inc.

!
Chemical
structural
formula
representation
Hazard
The
toxicology
database
for
zinc
pyrithione
is
adequate
for
the
current
registered
uses,
but
uncertainty
factors
were
applied
for
lack
of
adequate
characterization
of
neurotoxicity
of
zinc
pyrithione.
Acute
and
sub­
chronic
neurotoxicity
data
will
be
requested
as
confirmatory
data
to
properly
characterize
the
dose­
response
relationship
that
exists
for
this
aspect
of
zinc
pyrithione
toxicity.
Developmental
neurotoxicity
data
requirements
are
held
in
"
reserve",
pending
the
results
of
the
requested
acute
and
subchronic
neurotoxicity
studies.

The
toxicology
database
for
zinc
pyrithione
indicates
that
by
the
oral
route,
zinc
pyrithione
is
moderately
toxic
(
LD50
is
267
mg/
kg;
Toxicity
Category
II)
but
that
acute
toxicity
by
the
dermal
route
is
not
as
significant
(
LD50
>
2000
mg/
kg;
Toxicity
Category
III).
Acute
toxicity
by
the
inhalation
route
is
also
relatively
low
(>
0.61
mg/
L;
Toxicity
Category
III).
Zinc
pyrithione
is
Page
6
of
27
a
severe
eye
irritant
(
Toxicity
category
I)
but
does
not
appear
to
demonstrate
significant
dermal
irritation
(
Toxicity
category
IV).
Zinc
pyrithione
does
not
demonstrate
dermal
sensitization
potential.

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),
but
by
the
oral
route,
toxicity
is
significantly
greater
(
increased
relative
organ
weights,
clinical
toxicity,
and
hindlimb
weakness
at
3.75
mg/
kg/
day).

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.
Intravenous
administration
of
5
mg/
kg
zinc
pyrithione
to
female
Yorkshire
pigs
produced
cholinergic
effects
lasting
for
30­
60
minutes
post­
dose
(
HED
document
003933).
Increased
salivation
was
reported
immediately
after
dosing
in
the
rat
developmental
toxicity
study
at
a
dose
of
3
mg/
kg/
day
(
MRID
#
42827904).
Subchronic
administration
of
zinc
pyrithione
at
3.75
mg/
kg/
day
has
been
shown
to
produce
hindlimb
weakness
(
HED
document
no.
003933).
Peripheral
neuropathy
in
the
form
of
axonal
degeneration
has
been
observed.
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.

Studies
with
zinc
pyrithione
were
not
available
to
assess
chronic
toxicity
and
carcinogenicity
for
this
chemical.
One
two
year
rat
study
is
available
from
the
1950'
s
for
zinc
pyrithione,
however,
this
study
had
several
deficiencies
including:
small
sample
size
(
n=
10/
sex/
dose),
inadequate
histopathological
evaluation,
no
dietary
analyses
of
dose
levels
administered,
no
clinical
chemistry
analysis,
no
food
consumption
data,
clinical
signs
were
not
recorded
and
only
3
out
of
10
male
control
rats
survived
(
Larson
1958).
Two
chronic
toxicity
and
carcinogenicity
studies
are
available
for
sodium
pyrithione:
one
oral
rat
gavage
study
and
a
mouse
dermal
study.
These
two
cancer
studies
for
sodium
pyrithione
showed
no
evidence
of
carcinogenicity,
but
the
dermal
study
did
not
achieve
the
maximum
tolerated
dose.
Therefore,
sodium
pyrithione
was
classified
as
a
Group
D
(
not
classifiable
as
to
carcinogenicity)
carcinogen
by
the
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee.

The
available
evidence
for
gene
mutations
using
the
Ames
Salmonella
test
system
suggests
that
zinc
pyrithione
is
negative
for
mutations
in
this
system.
In
a
Chinese
hamster
ovary
forward
gene
mutation
assay,
zinc
pyrithione
failed
to
induce
a
mutagenic
response
at
doses
which
included
cytotoxicity.
In
an
in
vivo
micronucleus
assay
in
mice,
there
was
no
evidence
of
a
Page
7
of
27
positive
effect.
Therefore,
the
data
indicate
that
zinc
pyrithione
is
negative
for
mutagenic
effects.

Human
Health
Risk
Assessment
TOXICITY
ENDPOINTS
The
toxicity
endpoints
used
in
this
document
to
assess
potential
risks
include
acute
and
chronic
dietary
reference
doses
(
RfDs),
and
short­,
intermediate­
and/
or
long­
term
incidental
oral,
dermal
and
inhalation
doses,
are
listed
in
Table
1
below.
The
EPA
Health
Effects
Division's
(
HED)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
selected
these
toxicity
endpoints
in
1999,
which
were
upheld
by
the
Antimicrobials
Division's
endpoint
selection
committee
(
ADTC)
in
2004.

Acute
and
Chronic
RfDs:
Because
zinc
pyrithione
causes
adverse
developmental
effects,
the
HIARC
identified
two
acute
dietary
acute
RfDs,
one
for
females
of
child
bearing
age
(
13­
50
years)
and
one
for
the
general
population.
The
acute
RfDs
are
0.0016
mg/
kg/
day
and
0.0025
mg/
kg/
day
for
females
(
13­
50
years)
and
the
general
population,
respectively.
The
female
(
13­
50
year)
aRfD
is
based
on
adverse
developmental
effects
(
increased
post
implantation
loss
and
decreased
viable
fetuses)
at
1.5
mg/
kg/
day
in
a
rabbit
developmental
study,
while
the
aRfD
for
the
general
population
is
based
on
increased
salivation
in
maternal
rats
at
3
mg/
kg/
day
in
a
rat
developmental
study.

The
chronic
RfD
is
0.0016
mg/
kg/
day
based
on
adverse
developmental
effects
in
the
rabbit
developmental
study.
An
uncertainty
factor
of
300
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variability,
and
3X
for
database
uncertainties)
was
applied
to
the
NOAEL
to
obtain
the
acute
and
chronic
RfDs.
A
database
uncertainty
factor
of
3X
is
applied
to
non­
occupational
risk
assessments
for
zinc
pyrithione,
due
to
the
lack
of
characterization
of
neurotoxic
doseresponse
relationships
for
zinc
pyrithione,
and
the
need
for
additional
neurotoxicity
testing.
A
3X
factor
for
lack
of
neurotoxicity
data
(
as
opposed
to
a
higher
factor
of
10X)
is
adequate
because
neurotoxicity
observed
in
the
available
data
occurs
at
similar
effect
levels
as
other
adverse
responses,
the
doses
and
endpoints
selected
for
dietary
and
non­
dietary
assessments
encompass
the
doses
at
which
neurotoxicity
is
observed,
there
is
no
quantitative
evidence
of
susceptibility
to
the
toxic
effects
of
zinc
pyrithione,
and
traditional
uncertainty
factors
afford
a
degree
of
protection
that
is
considered
conservative.

Incidental
oral
endpoints:
The
short­
term,
and
intermediate­
term
incidental
oral
endpoint
of
0.75
mg/
kg/
day
is
based
on
increased
salivation
in
maternal
rats
at
3
mg/
kg/
day
in
a
rat
developmental
study.

Dermal
endpoints:
The
short­
term,
intermediate­
term,
and
long­
term
dermal
endpoint
is
based
on
body
weight
decrements
observed
at
1000
mg/
kg/
day
in
a
subchronic
dermal
toxicity
study.
The
dermal
no­
observed­
adverse
effect
level
(
NOAEL)
is
100
mg/
kg/
day.
Page
8
of
27
Inhalation
endpoints:
The
short­,
intermediate
and
long­
term
inhalation
endpoint
of
0.13
mg/
kg/
day
(
0.0005
mg/
L,
the
NOAEL)
is
based
on
labored
breathing,
rales,
increased
salivation,
decreased
activity,
dry
red­
brown
material
around
the
nose,
increased
absolute
and
relative
lung
weights,
and
death
of
undetermined
cause
at
0.0025
mg/
L
(
0.65
mg/
kg/
day)
in
a
whole
body
subchronic
rat
inhalation
study.

Table
1.
Toxicological
Endpoints
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
Females
13
­
50
years)
NOAEL
=
0.5
mg/
kg/
day
UF
=
100
DB=
3x
Acute
RfD=
0.0016
mg/
kg/
day
FQPA
SF
=
1x
aPAD=
acute
RfD
FQPA
SF
=
0.0016
mg/
kg/
day
Developmental
Toxicity
Study
in
Rabbits
LOAEL
=
1.5
mg/
kg/
day,
based
on
increased
post­
implantation
loss
and
decreased
viable
fetuses
Acute
Dietary
(
General
population,
including
infants/
children)
NOAEL
=
0.75
mg/
kg/
day
UF
=
100
DB=
3x
Acute
RfD=
0.0025
mg/
kg/
day
FQPA
SF
=
1x
aPAD=
acute
RfD
FQPA
SF
=
0.0025
mg/
kg/
day
Developmental
Toxicity
Study
in
Rats
LOAEL
=
3.0
mg/
kg/
day
based
on
increased
salivation
in
maternal
rats.

Chronic
Dietary
(
all
populations)
NOAEL
=
0.5
mg/
kg/
day
UF
=
100
DB=
3x
Chronic
RfD=
0.0016
mg/
kg/
day
FQPA
SF
=
1x
cPAD=
chronic
RfD
FQPA
SF
=
0.0016
mg/
kg/
day
Developmental
Toxicity
Study
in
Rabbits
LOAEL
=
1.5
mg/
kg/
day,
based
on
increased
post­
implantation
loss
and
decreased
viable
fetuses
Incidental
Oral,
Short­
and
Intermediate­
Term
Maternal
NOAEL=
0.75
mg/
kg/
day
Target
MOE
=
300
(
residential)
Developmental
Toxicity
Study
in
Rats
LOAEL
=
3.0
mg/
kg/
day,
Based
on
increased
salivation
in
maternal
rats.

Short­,
Intermediate­
,
and
Long­
Term
Dermal
Dermal
NOAEL
=
100
mg/
kg/
day
Target
MOE
=
300
(
residential)
100
(
occupational)
90­
Day
Subchronic
Dermal
Toxicity
in
Rats
LOAEL
=
1000
mg/
kg/
day,
based
on
decreased
body
weight
gain,
food
consumption,
and
food
Page
9
of
27
efficiency
in
female
rats.

Short­,
Intermediate­
,
and
Long­
Term
Inhalation
Inhalation
NOAEL
=
0.0005
mg/
L
(
0.13
mg/
kg/
day)
Target
MOE
=
300
(
residential)
100
(
occupational)
90­
Day
Subchronic
Inhalation
Toxicity
Study
in
Rats
LOAEL
=
0.0025
mg/
L
(
0.65
mg/
kg/
day)
based
on
clinical
signs
of
toxicity,
decreased
activity,
and
increased
lung
weights.

FQPA
SAFETY
FACTOR.
In
2003,
the
ADTC
committee
concluded
that
the
hazard
based
FQPA
safety
factor
can
be
reduced
to
1X
because
the
degree
of
concern
is
low
(
i.
e.
a
complete
developmental
and
reproductive
database
is
available
with
clear
NOAELs/
LOAELs
for
parental
and
offspring
toxicity)
and
there
are
no
residual
uncertainties
for
prenatal
toxicity.
The
developmental
toxicity
database
shows
effects
in
offspring
at
similar
dose
levels
as
effects
in
adults,
while
a
reproductive
toxicity
study
for
sodium
pyrithione
(
a
structurally
related
chemical)
shows
effects
in
offspring
at
doses
above
those
occurring
in
parental
animals.
Effects
observed
in
offspring
from
developmental
toxicity
studies
have
been
selected
for
use
in
dietary
risk
assessments,
thus
being
protective
of
infants
and
children.

Based
on
Agency
policy,
a
RfD
modified
by
a
FQPA
safety
factor
is
a
population
adjusted
dose
(
PAD).
The
Agency
calculated
an
acute
PAD
(
aPAD)
and
a
chronic
PAD
(
cPAD),
and
uses
this
value
to
estimate
acute
and
chronic
dietary
risk.
The
acute
PAD
is
the
acute
RfD
divided
by
the
FQPA
safety
factor.
The
cPAD
is
the
chronic
RfD
divided
by
the
FQPA
safety
factor.

DIETARY
(
FOOD)
RISK
ASSESSMENTS
EPA
considered
potential
dietary
exposure
to
zinc
pyrithione
residues
in
food
(
see
Table
2
below)
and
water.
When
assessing
acute
and
chronic
(
non­
cancer)
dietary
risk,
EPA
considered
potential
dietary
exposure
to
the
U.
S.
population
including
infants
and
children
as
well
as
to
females
13­
50
years,
based
on
the
developmental
toxicity
potential
of
this
active
ingredient.
EPA
expresses
dietary
risk
estimates
as
a
percentage
of
the
aPAD
or
cPAD.
Dietary
exposures
that
are
less
than
100%
of
the
aPAD
or
cPAD
are
below
the
Agency's
level
of
concern.
Estimates
of
dietary
risk
are
based
upon
the
detailed
analysis
in
the
residue
chemistry
chapter
(
memo
from
N.
Shamim
to
J.
Fairfax,
D251938).

Acute
Dietary
Risk.
Acute
dietary
risks
were
calculated
from
use
of
zinc
pyrithione
as
an
antimicrobial
pesticide
in
food
packaging
materials
and
repeat
use
of
polymeric
food
contact
materials.
Dietary
exposure
to
zinc
pyrithione
can
result
from
migration
of
the
active
ingredient
from
the
treated
article.
EPA
has
determined
that,
based
on
the
assumptions
and
models
used,
the
acute
dietary
risk
from
exposure
to
zinc
pyrithione
does
not
exceed
the
Agency's
level
of
concern
for
all
subpopulations
examined.
The
highest
dietary
risk
estimate
is
2.7%
of
the
acute
PAD,
for
infants
and
children.
Page
10
of
27
Chronic
Dietary
Risk.
The
acute
dietary
risk
analysis
are
used
to
assess
potential
chronic
dietary
exposure.
The
risk
analysis
assumes
daily
exposure
from
contact
with
polymeric
treated
articles
that
come
into
contact
with
food.
The
chronic
non­
cancer
dietary
analysis
indicates
all
risk
estimates
are
below
the
Agency's
level
of
concern
for
all
population
subgroups.
The
highest
dietary
risk
estimate
is
4.2%
of
the
chronic
PAD,
for
infants
and
children.

Table
2.
Summary
of
Dietary
Exposure
and
Risk
for
Zinc
Pyrithione
Population
Subgroup**
Acute
Dietary
Chronic
Dietary
Dietary
Exposure
(
mg/
kg/
day)
a
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
adult
male
2.8x10­
5
1.1
2.8x10­
5
1.8
females
(
13­
50
years)
3.3x10­
5
2.1
3.3x10­
5
2.1
infants/
children
6.7x10­
5
2.7
6.7x10­
5
4.2
a­­
acute
and
chronic
exposure
analysis
based
on
daily
consumption
of
0.002
mg/
person/
day
for
adults
and
body
weights
of
70
kg
and
60
kg
for
males
and
females,
respectively.
For
infants/
children,
exposure
based
on
daily
consumption
of
0.00067
mg/
person/
day;
and
a
10
kg
body
weight.
b­­
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
aPAD
or
cPAD,
where
aPAD=
0.0025
mg/
kg/
day
for
general
population;
aPAD=
0.0016
for
females
of
child
bearing
age;
and
cPAD=
0.0016
mg/
kg/
day
Drinking
Water
Dietary
Risk.
Certain
surface
waters
destined
for
drinking
water
can
be
exposed
to
zinc
pyrithione
from
the
leaching
from
antifoulant
boat
paints.
To
assess
drinking
water
impact,
the
Agency
estimated
predicted
environmental
concentrations
(
PEC's)
that
range
from
0.0144
to
0.101
ppb
zinc
pyrithione,
using
conservative
assumptions
and
the
Marine
Antifoulant
Model­
Predicted
Environmental
Concentration
(
MAM­
PEC)
model.
Because
there
is
a
lack
of
data
for
zinc
pyrithione
concentrations
in
fresh
waters,
the
PECs
estimated
by
MAMPEC
were
used
to
assess
potential
drinking
water
exposures
the
could
result
from
antifoulant
paint
on
boats
in
fresh
water
such
as
lakes
and
rivers.
The
PECs
were
used
to
assess
both
acute
and
chronic
drinking
water
exposures.
Based
on
current
Agency
policy,
drinking
water
level
of
comparison
(
DWLOCs)
are
compared
to
the
PEC.
When
the
PEC
is
greater
than
the
DWLOC,
EPA
considers
the
estimate
of
aggregate
risk
to
exceed
the
Agency's
level
of
concern
and
would
be
unacceptable.
(
See
Aggregate
Discussion
below
for
results
of
aggregate
dietary,
drinking
water
and
residential
risk).

Details
of
the
water
exposure
estimates
are
present
in
the
memorandum
(
memo
from
S.
Mostaghimi
to
D.
Smegal,
D301373,
April
2004),
while
details
on
chemical­
specific
inputs
into
the
models
are
presented
in
the
Environmental
Fate
Chapter
(
memo
from
N.
Shamim
to
D.
Smegal,
D301372,
April
2004).
Page
11
of
27
Exposure
Risk
Assessment
Residential
(
Non­
Occupational)
Exposure
and
Risk
Zinc
pyrithione
is
incorporated
into
many
substrates
that
can
result
in
non­
dietary
exposure,
such
as
footwear,
shower
curtains,
plastic
toys,
rubber
gloves,
carpet
fibers,
synthetic
floor
coverings,
plastic
furniture,
mattress
liners/
ticking/
covers,
paints,
sealants
and
caulks,
etc.
The
Agency
evaluated
potential
post­
application
exposures
to
these
consumer
products
that
contain
zinc
pyrithione.
Scenarios
evaluated,
which
were
considered
to
be
representative
of
all
possible
exposure
scenarios,
included:
dermal
and
inhalation
exposure
to
residential
handlers
during
painting
activities,
dermal
contact
with
treated
shoe
sole
liners,
incidental
ingestion
of
residues
on
treated
toys
(
i.
e.,
object­
to­
mouth),
and
incidental
ingestion
of
residues
on
hands
(
i.
e.,
hand­
to­
mouth)
from
contact
with
treated
toys/
objects.

The
Agency
also
evaluated
exposures
to
residential
handlers
that
could
use
zinc
pyrithione­
containing
antifoulant
paints
on
recreational
boats,
or
other
paints
or
consumer
products
that
contain
zinc
pyrithione
as
a
material
preservative.
Details
of
the
residential
exposure
assessment
can
be
found
within
the
companion
memorandum
(
memorandum
from
D.
Aviado/
D.
Smegal,
D301370,
April
2004),
and
in
Tables
3
and
4,
below.

Duration
of
exposure
is
short­
term
(
1­
30
days)
for
residential
handler
dermal
and
inhalation
exposure,
and
short­,
and
intermediate­
term
(
1
­
6
months)
for
incidental
oral
postapplication
exposures
to
children.
Dermal
exposures
from
postapplication
contact
were
considered
to
represent
a
long­
term
scenario
(>
6
months).
The
scenarios
were
evaluated
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs),
product
label
maximum
application
rates,
related
use
information,
Agency
standard
assumptions,
and
Pesticide
Handlers
Exposure
Database
(
PHED)
unit
exposure
data
(
for
residential
handlers).

Residential
postapplication
exposures
show
that
short­,
intermediate­,
and
long­
term
dermal
risks
are
not
of
concern
(
i.
e.
MOEs
>
300)
for
adult/
child
contact
with
zinc
pyrithionetreated
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
tomouth
exposures.

Residential
handler
exposure
scenarios
with
risk
estimates
that
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOEs
<
300)
are
related
to
the
use
of
zinc
pyrithione
in
paints:

°
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,
and
inhalation
MOE=
15;

°
Residential
handlers
that
paint
using
a
brush
(
antifoulant
paint
use
for
all
boat
sizes:
dermal
MOE=
22­
120;
inhalation
MOE=
18­
97
using
PHED
and
inhalation
Page
12
of
27
MOE=
5­
140
using
Health
and
Safety
Executive
(
HSE)
data
(
Garrod
et
al.
2000).

°
Residential
handlers
that
paint
using
an
aerosol
spray
can
(
inhalation
MOE=
271).
These
risk
estimates
are
based
on
a
number
of
conservative
assumptions.
For
example,
the
inhalation
endpoint
is
based
on
a
whole
body
rat
90­
day
inhalation
study,
while
there
is
a
full
10­
fold
factor
between
the
dermal
NOAEL
(
100
mg/
kg/
day)
and
the
lowest
observed
adverse
effect
level
(
LOAEL)
(
1000
mg/
kg/
day).

The
Agency
also
assessed
residential
dermal
exposure
from
use
of
zinc
pyrithionecontaining
shampoo.
Although
not
a
registered
use
under
the
EPA's
authority,
non­
dietary
nonpesticidal
use
of
zinc
pyrithione
in
anti­
dandruff
shampoo
was
considered
in
the
aggregate
risk
assessment.
The
Agency
evaluated
a
conservative
screening­
level
scenario
involving
once­
daily
use
of
zinc
pyrithione­
containing
shampoo.
The
estimated
dermal
MOE
is
3,300,
based
on
conservative
assumptions,
and
the
results
of
a
study
that
measured
radioactivity
associated
with
metabolized
zinc
pyrithione
(
zinc
pyrithione)
in
the
urine
for
5
days
following
a
single
shampoo
application
containing
radiolabeled
zinc
pyrithione.

Table
3.
Summary
of
Short­,
and
Intermediate­
Term
Residential
Post­
application
Exposure
and
Risks
(
c)

Scenario
Receptor
Use
Potential
Dosea
(
mg/
kg/
day
)
Dermal
MOEb
Target
MOE

300
Oral
MOEb
Target
MOE

300
Dermal
Contact
to
Rubber/
Plastic
Incorporated
with
Preservative
Adult
Rubber/
Plastic
(
Shoe
Liner)
1.3E­
2
7,700
NA
Toddlers
2.2E­
2
4,500
NA
Non­
Dietary
Ingestion
Toy­
to­
Mouth
Infants
Rubber/
Plastic
0.0004
NA
2,000
Non­
Dietary
Ingestion
Hand­
to­
Mouth
Infants
Rubber/
Plastic
0.0003
NA
2,500
Total
Exposure
and
Risk
Infant
Rubber/
Plastic
0.0007
(
total
oral)
NA
1,100
Toddler
2.2E­
2
(
dermal)
4,500
NA
Adult
1.3E­
2
(
dermal)
7,700
NA
Table
3
footnotes:
Page
13
of
27
NA
=
Not
applicable.
a
PDR
calculations
for
each
scenario
above
are
outlined
in
the
attached
Occupational/
Residential
Assessment
(
memo
from
D.
Aviado/
D.
Smegal,
April
2004
b
MOE=
NOAEL
(
mg/
kg/
day)
/
PDR
(
mg/
kg/
day).
Dermal
NOAEL
is
100
mg/
kg/
day;
oral
NOAEL
general
population
and
children
is
0.75
mg/
kg/
day.
c
Dermal
risks
are
also
for
long­
term
exposures.

Table
4
Estimates
of
Exposures
and
Risks
to
Residential
Handlers
of
Zinc
Pyrithione
Scenarioa
Dermal
Dose
(
mg/
kg/
day)
b
Inhalation
Dose
(
mg/
kg/
day)
c
Dermal
MOE
d
Acceptable
MOE

300
Inhalation
e
MOE
Acceptable
MOE

300
Residential
Handlers:
Do­
it­
Yourself
Boat
Hull
Painters
(
Antifoulant
Use)
[
EPA
Reg
Nos.
64684­
4
(
4.8%
ai)
and
2693­
194
(
47%
ai)]
All
Estimates
Based
on
3
Coats
of
Paint
in
One
Day
(
1a)
Brush
f
(
PHED)
4.5­
0.86
0.0071­
0.0013
22­
120
18­
97
(
1b)
Brush
f
(
Garrod
et
al.
2000)
Not
evaluated
(
exposure
data
of
insufficient
quality)
2­
6
hours
of
painting
Not
evaluated
5­
140
(
2)
Airless
Sprayer
f
0.96­
0.18
0.021­
0.004
100­
550
6­
33
Residential
Handlers:
Paints
Containing
Zinc
Pyrithione
(
Materials
Preservative
Use)

(
3)
Handling
zinc
pyrithione­
containing
paint
end
products
using
a
paint
brush
application
method
0.328
4.0E­
4
304
325
(
4)
Handling
zinc
pyrithione­
containing
paint
end
products
using
an
airless
sprayer
application
method
0.846
8.89E­
3
118
15
(
5)
Handling
zinc
pyrithione­
containing
paint
end
products
using
an
aerosol
spray
can
application
method
0.044
4.80E­
4
2,273
271
Table
4
Footnotes:
a
Scenarios
based
on
use
patterns
described
on
labels
and
LUIS
report.
Secondary
residential
handlers
include
homeowners
who
apply
products
containing
zinc
pyrithione
incorporated
as
a
general
preservative
for
paint.
b
Dermal
Dose
(
mg/
kg/
day)
=
[
Unit
Dermal
Exposure
(
mg/
lb
ai)
*
Use
Rate
(
lb
ai/
lb
product
or
lb
ai/
gal
product)
*
Amount
Handled
per
Day
(
lb
product/
day)]
/
Body
Weight
(
kg).
*
Use
of
gloves
as
PPE
assumes
a
90%
protection
factor.
Page
14
of
27
c
Inhalation
Dose
(
mg/
kg/
day)
=
[
Unit
Inhalation
Exposure
(
mg/
lb
ai)
*
Use
Rate
(
lb
ai/
lb
product
or
lb
ai/
gal
product)
*
Amount
Handled
per
Day
(
lb
product/
day)]
/
Body
Weight
(
kg).**
Use
of
organic
vapor
respirator
as
PPE
assumes
a
90%
protection
factor.
d
Dermal
MOE
=
Dermal
NOAEL
(
mg/
kg/
day)
/
Dermal
Dose
(
mg/
kg/
day).
Where
the
dermal
NOAEL
is
100
mg/
kg/
day.
e
Inhalation
MOE
=
Inhalation
NOAEL
(
mg/
kg/
day)
/
Inhalation
Dose
(
mg/
kg/
day).
Where
the
inhalation
NOAEL
of
0.0005
mg/
L/
day
is
converted
to
0.13
mg/
kg/
day,
or
the
route­
specific
inhalation
MOE
=
(
0.5
mg/
m3
x
6
hrs/
day
animal)
/
[(
paint
air
conc
mg/
3/%
ai
x
%
ai
in
paint
x
hrs
painting)
x
(
1
m3
work
breathing
rate
/
0.4
m3
resting
breathing
rate)].
Note:
The
route­
specific
inhalation
MOEs
do
not
coincide
with
the
route­
extrapolation
inhalation
MOEs
because
of
the
differences
in
methodologies
(
e.
g.,
UE,
dose
vs
air
conc,
estimates
of
hours
painting
versus
amount
of
ai
handled].
f
Dermal
and
Inhalation
doses
and
MOEs
vary
depending
on
boat
size.
Boat
sizes
assessed
are
14ftx5ft,
20
ftx8
ft,
and
30ftx10ft.

Aggregate
Exposure
and
Risk:
The
aggregate
risk
assessment
includes
combined
exposures
from
indirect
food
contact,
drinking
water,
and
non­
dietary
(
residential)
uses.
It
is
inappropriate
to
aggregate
oral,
dermal
and
inhalation
exposures
because
of
different
toxicological
endpoints
for
the
oral
(
salivation
and
developmental
effects),
dermal
(
decreased
body
weight
and
food
consumption)
and
inhalation
(
clinical
signs
of
toxicity,
and
lung
effects)
exposure
routes.

Acute.
The
acute
aggregate
food
(
from
indirect
food
contact)
and
drinking
water
exposure
(
from
antifoulant
paint
use)
do
not
exceed
the
Agency's
level
of
concern
for
adults
or
children
as
indicated
in
Table
5
below.
Percentages
of
the
acute
PAD
occupied
from
food
sources
were
highest
for
infants
and
children
(
2.7%),
and
were
less
for
adult
males
and
females
13­
50
years.
All
of
the
acute
DWLOCs
(
24­
86
ppb)
are
greater
than
the
PECs
of
0.0144
to
0.101
ppb,
indicating
that
aggregate
exposures
are
not
of
concern.

Table
5.
DWLOCs
for
Acute
Aggregate
Dietary
Exposure
Population
Subgroup
Acute
Scenario
aPAD
mg/
kg/
day
Acute
Food
Exp
mg/
kg/
day
Max
Acute
Water
Exp
mg/
kg/
day1
Surface
Water
PEC
(

g/
L)
2
Acute
DWLOC
(

g/
L)
3
Potential
Risk
Concern
4
Males
0.0025
0.000028
0.00247
0.0144­
0.101
86
No
Females
13­
50
years
0.0016
0.000033
0.001567
47
No
Infants/
Children
0.0025
0.000067
0.00243
24
No
Table
5
footnotes;

1
Maximum
acute
water
exposure
(
mg/
kg/
day)
=
[(
acute
PAD
(
mg/
kg/
day)
­
acute
food
exposure
(
mg/
kg/
day)]
2
Based
on
sea
water
for
antifoulant
use
on
recreational
boats.
3
Acute
DWLOC(

g/
L)
=
[
maximum
acute
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
Page
15
of
27
[
water
consumption
(
L/
day)
x
10­
3
mg/

g]
where
body
weight
is
70
kg,
60
kg
and
10
kg
for
adult
males,
females
and
children,
respectively
and
drinking
water
intake
rates
are
2
L/
day
and
1L/
day
for
adults
and
children,
respectively.
4
Does
the
surface
water
PEC
exceed
the
acute
DWLOC?

Short
and
Intermediate
Term.
Short­
and
intermediate­
term
aggregate
risk
assessments
includes
average
dietary
exposures
from
food
and
water,
in
addition
to
residential
exposures
(
if
applicable).
However,
because
the
toxicological
endpoints
are
different
for
oral
(
salivation
and
developmental
effects),
dermal
(
decreased
body
weight
and
food
consumption),
and
inhalation
(
clinical
signs
of
toxicity
and
lung
effects)
exposures,
potential
dietary
(
oral)
exposures
were
not
aggregated
with
potential
dermal
or
inhalation
exposure
from
residential
use.
However,
all
oral
exposures
were
aggregated
in
Table
6
below
(
i.
e.,
food,
drinking
water,
hand­
to­
mouth,
and
toyto
mouth),
while
a
separate
dermal
aggregate
assessment
was
conducted
to
assess
dermal
residential
exposures
(
i.
e.,
shoe
liners,
painting,
and
anti­
dandruff
shampoo).

ORAL.
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.
It
should
be
noted
that
several
conservative
assumptions
were
used
in
this
assessment.

DERMAL.
Two
separate
dermal
aggregate
MOEs
are
presented
because
it
was
assumed
that
a
resident
would
apply
paint
using
either
a
paintbrush
or
an
aerosol
can.
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
antidandruff
shampoo
are
greater
than
the
target
MOE
of
300,
and
thus
do
not
exceed
the
Agency's
level
of
concern.

However,
if
an
adult
resident
applies
paint
using
a
paintbrush
the
dermal
aggregate
MOEs
are
slightly
less
than
the
target
MOE
of
300
(
270)
and
are
of
concern.
In
addition,
it
should
be
noted
that
dermal
risks
are
already
of
concern
for
residents
that
could
apply
antifoulant
paint
to
their
boats
(
dermal
MOEs
range
from
22­
120
for
a
paintbrush,
and
100
for
an
airless
sprayer
for
larger
boats),
or
use
an
airless
sprayer
to
apply
products
when
zinc
pyrithione
is
used
as
a
material
preservative.
Thus,
these
scenarios
were
not
considered
in
the
aggregate
risk
assessment.
A
number
of
conservative
assumptions
were
used
in
calculating
the
dermal
aggregate
risk
estimates.

INHALATION.
The
only
uses
which
pose
inhalation
exposure
are
from
the
residential
handler
uses
of
paint,
which
have
MOEs
that
exceed
the
Agency's
level
of
concern
(
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.
Page
16
of
27
Table
6.
Summary
of
Oral
Short­
and
Intermediate­
Term
(
ST/
IT)
Aggregate
Exposure
and
DWLOC
Calculations
Populatio
n
Subgroup
ST/
IT
NOAEL
(
mg/
kg/
day)/
Target
MOE
Chronic
Food
Exp
mg/
kg/
day/
(
MOE)
ST/
IT
Oral
Residential
Exposure
(
mg/
kg/
day)/
(
MOE)
MOE
Water
Exp1
Allowable
ST/
IT
Water
Exp
(
mg/
kg/
day)
6
Surface
Water
PEC
(

g/
L)
2
ST/
IT
DWLOC
(

g/
L)
3
Potential
Risk
Concern4
Males
0.75/
300
0.000028/
(
26785)
NA
306
0.0024
0.0144­
0.101
86
No
Females
13­
50
years
0.000033/
(
22727)
NA
307
0.0024
73
No
Infants/
Children
0.000067/
(
11195)
0.0007/
(
1100)
5
434
0.0017
17
No
Table
6
footnotes:
ST=
short­
term;
IT=
intermediate
term
NA=
Not
applicable,
no
residential
incidental
oral
exposure
expected.
1
MOE
water
=
1
/
[
1/
MOE
aggregate
­
(
1/
MOE
food
+
1/
MOE
oral
res)]
2
Based
on
sea
water
for
antifoulant
use
on
recreational
boats.
3
ST/
IT
DWLOC(

g/
L)
=
[
maximum
ST/
IT
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
[
water
consumption
(
L/
day)
x
10­
3
mg/

g]
where
body
weight
is
70
kg,
60
kg
and
10
kg
for
adult
males,
females
and
children,
respectively
and
drinking
water
intake
rates
are
2
L/
day
and
1L/
day
for
adults
and
children,
respectively.
4
Does
the
surface
water
PEC
exceed
the
DWLOC?
5
Based
on
total
oral
exposure
for
infants/
children
on
Table
3
for
zinc
pyrithione
treated
toys.
6
Short­
term
oral
NOAEL
(
0.75
mg/
kg/
day)
/
MOE
aggregate.

Chronic.
Chronic
aggregate
risk
determines
the
combined
risk
from
average
daily
exposure
in
the
diet
(
food
+
water)
with
those
exposures
arising
as
a
result
of
residential
uses
(
if
applicable).
This
assessment
includes
chronic
food
and
drinking
water
exposures
because
the
long­
term
residential
exposures
are
through
the
dermal
route
of
exposure
(
i.
e.,
anti­
dandruff
shampoo
use,
or
shoe
liner
exposure),
which
should
not
be
aggregated
with
oral
exposures
due
to
different
toxicological
endpoints.

As
noted
previously,
chronic
dietary
exposures
do
not
exceed
the
Agency's
level
of
concern
(
highest
exposure
represents
4.2%
of
the
cPAD
for
infants
and
children).
The
chronic
DWLOCs
are
greater
than
the
PEC
for
adults
and
infants/
children
(
see
Table
7
below),
indicating
that
aggregate
food
and
drinking
water
exposure
do
not
exceed
the
Agency's
level
of
concern.
These
results
are
based
upon
a
number
of
conservative
assumptions
regarding
dietary
and
water
exposure
and
do
not
necessarily
represent
the
most
refined
drinking
water
assessment.
Page
17
of
27
Table
7.
DWLOCs
for
Chronic
Aggregate
Exposure
Population
Subgroup
Chronic
Scenario
cPAD
mg/
kg/
day
Chronic
Food
Exp
mg/
kg/
day
Max
Chronic
Water
Exp
mg/
kg/
day1
Surface
Water
PEC
(
ppb)
2
Chronic
DWLOC
(

g/
L)
3
Potential
Risk
Concern4
Males
0.0016
0.000028
0.00157
0.0144­
0.101
55
No
Females
13­
50
years
0.000033
0.00156
47
No
Infants/
Children
0.000067
0.00153
15
No
Table
7
footnotes:
1
Maximum
chronic
water
exposure
(
mg/
kg/
day)
=
[(
chronic
PAD
(
mg/
kg/
day)
­
chronic
food
exposure
(
mg/
kg/
day)]
2
Based
on
sea
water
for
antifoulant
use
on
recreational
boats.
3
Chronic
DWLOC(

g/
L)
=
[
maximum
chronic
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
[
water
consumption
(
L/
day)
x
10­
3
mg/

g]
where
body
weight
is
70
kg,
60
kg
and
10
kg
for
adult
males,
females
and
children,
respectively
and
drinking
water
intake
rates
are
2
L/
day
and
1L/
day
for
adults
and
children,
respectively.
4
Does
the
surface
water
PEC
exceed
the
chronic
DWLOC?

OCCUPATIONAL
EXPOSURE
AND
RISK.
The
Agency
has
determined
that
there
is
potential
for
worker
exposure
to
zinc
pyrithione
through
mixing,
loading,
application,
and
handling
activities
associated
with
zinc
pyrithione
pesticide
products.
There
are
potential
exposures
from
use
in
commercial,
and
industrial
settings
via
the
dermal
and
inhalation
routes.
Based
on
the
EPA­
registered
use
patterns,
appropriate
primary
and
secondary
handler
exposure
scenarios
were
identified
for
zinc
pyrithione.
An
exposure/
risk
assessment
for
occupational
antifoulant
boat
paint
use,
which
is
subject
to
a
timelimited
registration,
was
not
included
in
this
assessment
but
will
be
evaluated
later,
following
the
submission
of
relevant
worker
exposure
data
for
this
use.

In
general
terms,
EPA
defines
"
primary"
handler
exposure
as
direct
exposure
to
the
pesticide
formulation
during
mixing/
loading/
applying
operations.
"
Secondary"
handler
exposure
is
defined
as
exposure
to
a
pesticide
active
ingredient
as
a
direct
result
of
its
incorporation
into
an
end
product.
Examples
of
secondary
handler
exposure
include
the
application
of
treated
paints
and
coatings,
and
building
materials
such
as
caulks,
adhesives,
spackling,
groutings,
sealants,
stucco
and
joint
cements.
Based
on
end­
use
product
application
methods
and
use
amounts,
it
is
assumed
that
exposures
while
applying
paints
will
be
equal
to
or
greater
than
exposures
while
applying
building
materials.
Therefore,
occupational
handler
exposures
were
assessed
for
the
application
of
paint,
as
this
scenario
represents
maximum
possible
exposure
to
the
chemical.
Under
this
scenario,
dermal
and
inhalation
exposures
were
assessed
for
brush,
airless
sprayer,
and
aerosol
application
methods.
Page
18
of
27
The
exposure
and
risk
assessment
for
primary
and
secondary
occupational
handlers
(
see
Table
8
below)
was
conducted
using
product
label
maximum
application
rates,
related
use
information
from
the
technical
registrant
(
Arch
Chemicals,
Inc),
Agency
standard
values
for
industrial
practices,
unit
exposure
data
from
the
Chemical
Manufacturers
Association
(
CMA)
and
the
Pesticide
Handlers
Exposure
Database
(
PHED),
and
relevant
scientific
literature.

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
do
not
exceed
the
Agency's
level
of
concern
(
i.
e.,
target
MOEs

100)
for
the
dermal
and
inhalation
exposure
scenarios
assessed.
The
"
dermal"
exposure
risks
are
not
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
MOEs
which
are
of
concern
(
i.
e.,
MOEs
<
100):

°
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).

It
is
assumed
that
in
real­
use
situations
for
airless
sprayer
applications,
the
occupational
handlers
will
have
adequate
respiratory
protection
by
wearing
either
a
dust/
mist
or
organic
vapor
respirator
and
PPE
recommended
by
the
paint
manufacturers
for
spray
equipment
applications.
The
Agency
may
consider
requiring
risk
mitigation
steps,
such
as
closed
delivery
systems
and/
or
use
of
a
respirator
and
additional
PPE
during
open
pouring.
Although
the
dermal
MOE
for
airless
spray
painting
operations
is
of
concern
(
MOE=
74)
without
gloves,
the
MOE
is
not
of
concern
(
MOE
=
200)
when
gloves
are
worn
as
protective
equipment.
It
is
assumed
that
in
real­
use
situations
for
airless
sprayer
applications,
the
occupational
handlers
will
have
adequate
dermal
protection
by
wearing
gloves
as
may
be
recommended
by
paint
manufacturers
during
spray
equipment
applications.
Dermal
and
inhalation
MOEs
obtained
for
the
painting
scenarios
involving
use
of
paint
brush
and
aerosol
spray
can
application
methods
were
found
to
be
of
no
risk
concern.
Page
19
of
27
Primary
occupational
post­
application
dermal
and
inhalation
exposures
are
limited
to
mists,
steams,
or
vapors
resulting
from
manufacturing
process
operations.
These
exposures
are
likely
to
be
minimal
because
of
the
dilution
of
the
pesticide
during
processing
and
the
low
vapor
pressure
of
the
active
ingredient,
and
thus
were
not
quantitatively
evaluated
in
this
report.

Table
8.
Estimates
of
Exposures
and
Risks
to
Occupational
Handlers
of
Zinc
Pyrithione
Application
Scenario(
a)
Use
Rate
(
lb
ai/
1000
lb,
or
lb
ai/
100
gal)(
b)
Amount
Handled
(
lb/
day
or
gal/
day)(
c)
Dermal
MOE(
d)
Target
MOE

100
Inhalation
MOE(
e)
Target
MOE

100
Primary
Occupational
Handler:
General
Preservatives
Uses:
Dry
Film,
In
Can,
and
Material
Preservation
(
1a)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
open
pour
methods
5
lb
ai/
1,000
lb
10,000
lb/
day
1037
50
(
1b)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
metering
equipment
(
pump
liquid)
5
lb
ai/
1,000
lb
10,000
lb/
day
2.23E+
4
452
(
1c)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
open
pour
methods
5
lb
ai/
1,000
lb
10,000
lb/
day
300
15
(
1d)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
metering
equipment
(
automatic­
dispensing
techniques)
5
lb
ai/
1,000
lb
10,000
lb/
day
2.23E+
4
452
Primary
Occupational
Handler:
Paints:
Dry
Film
Preservation
(
2a)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
open
pour
methods
5
lb
ai/
100
gal
1,000
gal
1037
50
(
2b)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
metering
equipment
(
pump
liquid)
5
lb
ai/
100
gal
1,000
gal
2.23E+
4
452
(
2c)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
open
pour
methods
5
lb
ai/
100
gal
1,000
gal
300
15
(
2d)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
metering
equipment
(
automatic­
dispensing
techniques)
5
lb
ai/
100
gal
1,000
gal
2.23E+
4
452
Primary
Occupational
Handler:
Fabrics/
Textiles:
Laundering
Treatment
for
Material
Preservation
(
3a)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
open
pour
methods
0.25
lb
ai/
1,000
gal
1,000
gal
2.07E+
5
1.01E+
4
(
3b)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
metering
equipment
(
pump
liquid)
0.25
lb
ai/
1,000
gal
1,000
gal
4.45E+
6
9.03E+
4
Table
8.
Estimates
of
Exposures
and
Risks
to
Occupational
Handlers
of
Zinc
Pyrithione
Application
Scenario(
a)
Use
Rate
(
lb
ai/
1000
lb,
or
lb
ai/
100
gal)(
b)
Amount
Handled
(
lb/
day
or
gal/
day)(
c)
Dermal
MOE(
d)
Target
MOE

100
Inhalation
MOE(
e)
Target
MOE

100
Page
20
of
27
(
3c)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
open
pour
methods
1
lb
ai/
1,000
gal
1,000
gal
1.5E+
4
728
(
3d)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
metering
equipment
(
automatic­
dispensing
techniques)
1
lb
ai/
1,000
gal
1,000
gal
1.11E+
6
2.26E+
4
Secondary
Occupational
Handler:
Paints
Containing
Zinc
Pyrithione
(
Materials
Preservative)

(
4a)
Handling
zinc
pyrithionecontaining
paint
end
products
using
a
paint
brush
application
method
5
lb
ai/
100
gal
5
gal/
day
156
130
(
4b)
Handling
zinc
pyrithionecontaining
paint
end
products
using
an
airless
sprayer
application
method
5
lb
ai/
100
gal
50
gal/
day
74
4.4
200
(
PPE)
(
f)
44
(
PPE)(
f)

(
4c)
Handling
zinc
pyrithionecontaining
paint
end
products
using
an
aerosol
spray
can
application
method
5
lb
ai/
100
gal
0.28
gal/
day
(
3
12­
oz
cans)
2,632
500
Table
8
Footnotes:
(
a)
Scenarios
based
on
use
patterns
described
on
labels
and
LUIS
report.
Primary
occupational
handlers
include
people
who
add
zinc
pyrithione
as
a
general
preservative
to
products
such
as
food/
non­
food
contact
adhesives;
floor
tile
adhesives;
caulks
and
sealants;
grout
and
patching
compounds;
food/
non­
food
contact
polymeric
materials;
rubber
and
thermoplastic
resins;
preservatives
in
latex
paint;
architectural
coatings;
dry
film
preservative
in
products
such
as
dry
wall
and
building
materials;
and
laundered
fabrics.
(
b)
Represents
the
maximum
use
rates
on
the
registered
zinc
pyrithione
product
labels;
EPA
Registration
Nos.:
1258­
840
and
1258­
841.
(
C)
Standard
EPA
default
assumptions:
10,000
for
caulk;
1,000
for
paint;
and
1,000
for
laundered
fabric.
(
d)
Dermal
MOE
=
Dermal
NOAEL
(
mg/
kg/
day)
/
Dermal
Dose
(
mg/
kg/
day).
Where
the
dermal
NOAEL
is
100
mg/
kg/
day.
(
e)
Inhalation
MOE
=
Inhalation
NOAEL
(
mg/
kg/
day)
/
Inhalation
Dose
(
mg/
kg/
day).
Where
the
inhalation
NOAEL
of
0.0005
mg/
L/
day
is
converted
to
0.13
mg/
kg/
day.
(
f)
PPE
for
inhalation
is
organic
vapor
respirator,
which
provides
approximately
90%
protection.

CUMULATIVE
RISKS
Section
408
of
the
FFDCA
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.

The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
Page
21
of
27
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
zinc
pyrithione
has
a
common
mechanism
of
toxicity
with
other
substances
including
sodium
pyrithione.

Endocrine
Disruption
The
reproductive
and
growth
impacts
to
aquatic
organisms
(
see
Ecological
Risk
section
below)
indicate
that
zinc
pyrithione
is
a
potential
endocrine
disruptor.
The
Food
Quality
Protection
Act
(
FQPA;
1996)
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticides
and
inerts)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect.....".

Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
zinc
pyrithione
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

Ecological
Risk
A
detailed
ecological
hazard
and
environmental
risk
assessment
for
zinc
pyrithione
is
presented
in
the
review
of
K.
Montague
(
D301371,
April
2004),
while
the
detailed
information
on
environmental
fate
is
presented
in
the
review
of
N.
Shamim
(
D301372,
April
2004).
A
brief
summary
is
presented
below.
Because
the
antifoulant
boat
paint
use
is
a
conditional
and
timelimited
approval,
based
on
submission
of
acceptable
data
listed
in
the
section
below
titled
"
Summary
of
Pending
Confirmatory
Data",
this
use
will
be
fully
assessed
after
the
confirmatory
data
is
received.

ENVIRONMENTAL
FATE/
TRANSPORT
Page
22
of
27
Zinc­
pyrithione
is
a
complex
(
coordination)
compound
formed
through
a
chemical
reaction
between
the
inorganic
zinc
ion
and
organic
moiety
pyrithione.
Hydrolytically,
the
chemical
is
stable
in
water
under
abiotic
and
buffered
conditions
(
pH
5,
7
and
9),
as
well
as
in
simulated
sea
water.
The
extrapolated
hydrolyic
half­
lives
were
99,
120
and
123
days
at
a
pH
of
5,
7,
and
9,
respectively.
In
simulated
sea
water,
the
extrapolated
half
life
was
96
days.

Photolytic
measurements
showed
that
zinc
pyrithione
rapidly
degrades
rapidly
with
a
half
life
of
13
minutes
in
buffered
medium,
and
in
about
17
minutes
in
simulated
sea
water.

In
a
study
on
aerobic
aquatic
systems,
zinc
pyrithione
degradation
follows
a
biphasic
(
two
phase)
process.
In
the
first
phase
it
degrades
rapidly
with
a
half
life
of
about
4
minutes
in
salt
water,
and
in
about
1.3
hours
in
fresh
water
samples.
In
a
second
phase,
the
half­
lives
of
zinc
pyrithione
were
12.3
and
15
days
for
fresh
water,
and
sea
water
respectively.

In
a
study
on
anaerobic
aquatic
systems,
zinc
pyrithione
degradation
also
follows
a
biphasic
process.
In
the
first
phase
it
degrades
rapidly
with
a
half
life
of
about
2
hours
in
both
salt
and
fresh
water.
In
the
second
phase,
the
half­
lives
were
25
hours
for
fresh
water
and
sea
water.
In
anaerobic
sediment,
the
half
life
was
about
13
hours.

There
are
multiple
degradation
pathways
which
determine
the
concentration
of
zinc
pyrithione
in
the
environment.
Under
aerobic
conditions,
the
zinc
pyrithione
degradation
half
life
is
about
36
minutes
in
aqueous
systems,
and
is
about
21.3
hours
in
sediment.
Similarly,
zinc
pyrithione
shows
a
tendency
of
degrading
anaerobically
in
water
within
30
minutes,
and
in
about
19
hours
in
sediments.

Arch
Chemicals
submitted
an
outdoor
microcosm
study
(
MRID
45876501),
which
is
not
required
by
environmental
fate
requirements.
This
study
was
reviewed
and
found
deficient
in
many
ways.
However,
the
Agency
considers
this
data
to
be
supplemental.
The
study
indicates
that
zinc
pyrithione
degrades
under
simulated
seawater
conditions,
under
dark
or
in
the
presence
of
light.
The
half­
lives
under
all
conditions
were
less
than
24
hours.
The
study
also
indicates
that
zinc
pyrithione
shows
little
tendency
to
accumulate
in
sediment,
particularly
if
light
is
present.
These
results
provide
additional
support
to
the
findings
of
laboratory
studies
conducted
to
evaluate
the
various
degradation
pathways
for
zinc
pyrithione.

Zinc
pyrithione
shows
a
moderately
strong
tendency
to
bind
with
soils
and
sediments:
With
salt
water
soil
and
sediment,
its
K
d
s
are
50
and
99,
respectively.
Tendency
to
bind
with
freshwater
soils
and
sediments
are
less
strong
and
observed
K
d
s
are
11
and
48,
respectively.

The
reported
Octanol/
Water
Partition
coefficient
K
OW
is
<
1000
(
Log
Kow
is
0.97).
Zinc
pyrithione
is
therefore
not
expected
to
bioaccumulate
in
aquatic
organisms
(
fish
etc.).

ECOLOGICAL
HAZARD
AND
RISK
The
ecological
effects
database
for
zinc
pyrithione
is
adequate
to
support
the
indoor
uses
Page
23
of
27
considered
in
this
RED.
The
antifoulant
paint
use
expires
6/
30/
05
and
will
be
evaluated
upon
submission
of
the
required
confirmatory
ecotoxicity
and
worker
exposure
studies
listed
in
the
section
below
titled
"
Summary
of
Pending
Confirmatory
Data".

Zinc
pyrithione
is
moderately
toxic
to
birds
via
acute
oral
exposure,
and
slightly
toxic
to
practically
non­
toxic
to
birds
via
dietary
exposure.
It
is
also
acutely
toxic
to
mammals
via
oral
ingestion
(
Toxicity
Category
II).
Exposure
to
terrestrial
and
aquatic
organisms
and
plants
is
expected
to
be
minimal
from
the
registered
indoor
uses
of
zinc
pyrithione.
Risk
to
birds,
mammals,
fish,
aquatic
invertebrates,
and
plants,
including
endangered
species,
is
not
anticipated
from
the
indoor
uses
of
zinc
pyrithione.

However,
zinc
pyrithione
is
very
highly
toxic
on
an
acute
basis
at
low
ppb
concentrations
to
freshwater
and
marine
fish
and
invertebrates,
as
well
as
to
aquatic
plant
species
(
see
tables
9­
15
below).
It
has
been
shown
to
cause
adverse
chronic
impacts
on
freshwater
and
marine
invertebrate
reproduction
and
growth
at
very
low
concentrations.
These
adverse
growth
and
reproductive
effects
indicate
that
zinc
pyrithione
may
be
a
potential
human
endocrine
disrupter.

Table
9.
Freshwater
Fish
Acute
Toxicity
of
Zinc
Pyrithione
Species
%
ai
LC50
(
ppb
ai)
(
95
%
c.
i.)
NOAEC
(
ppb
ai)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Rainbow
trout
(
Oncorhynchus
mykiss)
97.8
3.6
(
3.07
­
4.33)
1.6
very
highly
toxic
43864613
Boeri/
1994
core
Fathead
minnow
(
Pimephales
promelas)
97.8
2.68
(
2.10
­
3.27)
1.1
very
highly
toxic
43864606
Boeri/
1994
core
Table
10.
Freshwater
Fish
Early
Life­
Stage
Toxicity
of
Zinc
Omadine
®
(
parent)

Species
%
ai
NOAEC/
LOAEC
(
ppb)
Endpoints
Affected
MRID
No.
Author/
Year
Study
Classification
Fathead
minnow
(
Pimephales
promelas)
98.2
1.22/
2.82
Survival,
sublethal
effects
(
bent
spinal
columns),
and
length
45204102
Boeri/
1999
core
Page
24
of
27
Table
11.
Freshwater
Invertebrate
Acute
Toxicity
of
Zinc
Pyrithione
(
parent)

Species
%
ai
LC50
or
EC50
(
ppb
ai)
(
95%
c.
i.)
NOAEC
(
ppb
ai)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Waterflea
(
Daphnia
magna)
97.8
8.25
(
5.24
­
25.82)
<
1.1
very
highly
toxic
43864604
Boeri/
1994
core
Freshwater
amphipod,
Hyalella
azteca
98.2
136
ppb
highly
toxic
449218­
01
Supplemental
Table
12.
Freshwater
Aquatic
Invertebrate
Life­
Cycle
Toxicity
of
Zinc
Pyrithione
Species
%
ai
NOAEC/
LOAEC
(
ppb)
Endpoints
Affected
MRID
No.
Author/
Year
Study
Classification
Waterflea
(
Daphnia
magna)
98.2
2.7/
5.8
reproduction
length
44535401
Boeri/
1998
core
Table
13
.
Acute
Toxicity
of
Zinc
Pyrithione
(
parent)
to
Estuarine/
Marine
Fish
Species
%
ai
LC50
(
ppb
ai)
(
95%
c.
i.)
NOAEC
(
ppb
ai)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Sheepshead
minnow
(
Cyprinodon
variegatus)
97.8
400
(
200­
590)
200
highly
toxic
43864605
Boeri/
1994
core
Table
14:
Acute
Toxicity
of
Zinc
Pyrithione
(
parent)
to
Estuarine/
Marine
Invertebrates
Species
%
ai.
96­
hour
LC50/
EC50
(
ppb)
(
95%
c.
i.)
NOAEC
(
ppb)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Eastern
oyster
(
Crassostrea
virginica)
shell
deposition
97.8
22.0
(
18.9
­
27.3)
7.1
very
highly
toxic
43864608
Boeri
et
al/
1994
core
Mysid
(
Mysidopsis
bahia)
97.8
4.7
(
4.04­
5.53)
1.6
very
highly
toxic
43864607
Boeri
et
al/
1994
core
Page
25
of
27
Table
15:
Acute
Toxicity
of
Zinc
Pyrithione
(
parent)
to
Alga
and
Aquatic
Plants
Species
%
ai.
96­
hour
LC50/
EC50
(
ppb)
(
95%
c.
i.)
NOEC
(
ppb)
MRID
No.
Author/
Year
Study
Classification
Freshwater
green
alga
(
Selenastrum
capricornutum)
97.8
28.0
(
24.3­
33.0)
7.8
43864609
Ward
et
al/
1994
core
Blue­
green
alga
(
Anabaena
flos­
aquae)
98.3
7.1
3.8
45564901
core
Freshwater
diatom
(
Navicula
pelliculosa)
98.3
2.6
2.4
45565001
core
Aquatic
vascular
plant,
duckweed
(
Lemna
gibba)
98.2
8.87
4.0
45204104
core
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,
because
zinc
pyrithione
degrades
fairly
quickly
in
both
freshwater
and
saltwater
soils
and
sediments,
and
the
predicted
environmental
concentrations
are
low,
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.

Due
to
the
high
toxicity
of
the
parent
compound
to
aquatic
organisms,
coupled
with
the
parent
compound's
tendency
to
break
down
fairly
rapidly
into
more
persistent
degradates
in
aquatic
systems,
aquatic
organism
acute
toxicity
tests
using
two
major
degradates
of
zinc
pyrithione
were
submitted.
These
data
indicate
that
both
pyridine
sulfonic
acid
and
pyrithione
sulfonic
acid
are
only
slightly
toxic
to
practically
non­
toxic
to
freshwater
and
marine/
estuarine
fish
and
invertebrates
and
aquatic
plants.

RISK
TO
ENDANGERED
SPECIES
The
Agency
has
developed
the
Endangered
Species
Protection
Program
to
identify
pesticides
whose
use
may
cause
adverse
impacts
on
endangered
and
threatened
species,
and
to
implement
mitigation
measures
that
address
these
impacts.
The
Endangered
Species
Act
requires
federal
agencies
to
ensure
that
their
actions
are
not
likely
to
jeopardize
listed
species
or
adversely
modify
designated
critical
habitat.
To
analyze
the
potential
of
registered
pesticide
uses
to
affect
any
particular
species,
EPA
puts
basic
toxicity
and
exposure
data
developed
for
risk
assessments
into
context
for
individual
listed
species
and
their
locations
by
evaluating
important
ecological
parameters,
pesticide
use
information,
the
geographic
relationship
between
specific
pesticide
uses
and
species
locations,
and
biological
requirements
and
behavioral
aspects
of
the
particular
species.
A
determination
that
there
is
a
likelihood
of
potential
impact
to
a
listed
species
may
result
in
Page
26
of
27
limitations
on
use
of
the
pesticide,
other
measures
to
mitigate
any
potential
impact,
or
consultations
with
the
Fish
and
Wildlife
Service
and/
or
the
National
Marine
Fisheries
Service
as
necessary.

The
Agency
is
currently
engaged
in
a
Proactive
Conservation
Review
with
USFWS
and
the
National
Marine
Fisheries
Service
under
section
7(
a)(
1)
of
the
Endangered
Species
Act.
The
objective
of
this
review
is
to
clarify
and
develop
consistent
processes
for
endangered
species
risk
assessments
and
consultations.
Subsequent
to
the
completion
of
this
process,
the
Agency
will
reassess
the
potential
effects
of
zinc
pyrithione
use
to
federally
listed
threatened
and
endangered
species.
Until
such
time
as
this
analysis
is
completed,
any
overall
environmental
effects
mitigation
strategy
developed
by
the
Agency
and/
or
any
County
Specific
Pamphlets
which
address
zinc
pyrithione,
or
other
boat
antifoulant
compounds,
will
serve
as
interim
protection
measures
to
reduce
the
likelihood
that
endangered
and
threatened
species
may
be
exposed
to
zinc
pyrithione
at
levels
of
concern.

Summary
of
Pending
Confirmatory
Data
There
is
concern
for
the
neurotoxic
effects
of
zinc
pyrithione
that
have
not
been
completely
characterized
in
the
available
toxicology
data.
Acute
and
subchronic
neurotoxicity
studies
(
870.6200)
are
thus
being
required
as
confirmatory
data
for
this
chemical
in
order
to
characterize
more
fully
this
type
of
toxicity.
Developmental
neurotoxicity
data
is
held
in
"
reserve",
pending
the
results
of
the
required
acute
and
subchronic
neurotoxicity
studies.

In
addition,
the
following
five
confirmatory
ecotoxicity
studies
were
submitted
too
late
to
be
part
of
this
RED.
The
cut­
off
date
for
incorporating
data
into
this
risk
assessment
was
4/
1/
04.

73­
1
Whole
sediment
acute
freshwater
invertebrate
73­
2
Whole
sediment
acute
marine
invertebrate
850.5400
Marine
diatom
Skeletonema
costatum
850.4225
Seedling
emergence
in
rice
850.4250
Vegetative
vigor
dose
response
in
rice
A
confirmatory
worker
exposure
study
is
currently
under
final
design
and
scheduling
to
support
the
conditional
registration
of
the
antifoulant
paint
use.
This
study
is
an
assessment
of
the
potential
inhalation
and
dermal
exposure
to
zinc
pyrithione
antifoulant
paints
during
outdoor
painting
of
large
ship
hulls.
It
is
required
to
be
submitted
by
1/
1/
05
and
must
satisfy
the
following
guideline
studies:

875.1200
Dermal
exposure
­
indoor
875.1400
Inhalation
exposure
­
indoor
875.1100
Dermal
exposure
­
outdoor
875.1300
Inhalation
exposure
­
outdoor
Page
27
of
27
The
following
antifoulant
use
related
data
are
considered
"
reserved"
at
this
time.
They
must
be
submitted
within
twelve
months
of
the
date
of
the
Agency's
written
request
for
these
data.
The
need
for
these
reserved
data
will
be
based
upon
the
results
of
one
or
more
of
the
above
confirmatory
or
base
studies,
as
determined
by
the
Agency.

GLN
72­
5
Fish
Life
Cycle
GLN
72­
7
Simulated
or
actual
field
testing
for
aquatic
organisms
GLN
71­
4
Avian
Reproduction
GLN
73­
3
Acute
Pore
Water
Studies
(
fish
and
invertebrates)
GLN
74­
1
Whole
Sediment
Chronic
Study
(
invertebrates)
Special
Study:
Monitoring
of
Representative
U.
S.
Waters
GLN
162­
1
Aerobic
Soil
Metabolism
GLN
162­
2
Anaerobic
Soil
Metabolism
GLN
164­
2
Aquatic
Field
Study
GLN
165­
5
Accumulation
Study
(
Nontarget
organism)
GLN
(
N/
A)
Monitoring
of
Representative
US
Waters