Document ID: EPA-HQ-OPP-2004-0147-0023
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-03-09T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
September
30,
2004
SUBJECT:
Zinc
Pyrithione
(
Zinc
Omadine
®
)
:
AD
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
Chemical
No.
088002.
Case
No.
2480.
DP
Barcode:
D308704
FROM:
Deborah
Smegal,
MPH,
Toxicologist/
Risk
Assessor
Timothy
F.
McMahon,
Ph.
D.,
Senior
Toxicologist
Doreen
Aviado,
Biologist
Kathryn
Montague,
M.
S.
Biologist
Najm
Shamim,
Ph.
D.
Chemist
Siroos
Mostaghimi,
Ph.
D.
Environmental
Engineer
Antimicrobials
Division
(
7510C)

THRU:
Norm
Cook,
Chief
Risk
Assessment
and
Science
Support
Branch
Antimicrobials
Division
(
7510C)

TO:
Tony
Kish
Regulatory
Management
Branch
I/
Team
33
Antimicrobials
Division
(
7510C)

Attached
is
RASSB's
Risk
Assessment
for
Zinc
Pyrithione
(
Zinc
Omadine
®
)
for
the
purpose
of
issuing
a
Reregistration
Eligibility
Decision
(
RED).
The
disciplinary
science
chapters
and
other
supporting
documents
for
the
zinc
omadine
RED
are
also
included
as
attachments
as
follows:
Zinc
Omadine:
Revised
Toxicology
Endpoint
Selection
Report
from
the
Antimicrobials
Divisions's
Toxicology
Endpoint
Selection
Committee
(
ADTC),
September
2004
Toxicology
Science
Chapter
for
the
Reregistration
Eligibility
Decision
Document,
From
T.
McMahon
to
D.
Smegal,
April
2004
D301369
Occupational
and
Residential
Exposure
Assessment
for
the
RED
Document.
From
D.
Aviado/
D.
Smegal
to
B.
Chambliss.
September
2004,
D308705
Residue
Chemistry
Science
Chapter
for
Zinc
2­
pyridinethiol­
1­
oxide.
From
A.
N.
Shamim
to
J.
Fairfax.
D251938
Environmental
Fate
Science
Chapter
for
Zinc
Omadine
for
Reregistration
Eligibility
Document
(
RED).
From
A.
N.
Shamim
to
D.
Smegal.
April
2004,
D301372
Predicted
Environmental
Concentration
(
PEC)
for
Zinc
Omadine
and
Tributyl
Tin
(
TBT).
From
S.
Mostaghimi
to
D.
Smegal.
April
2004,
D301373
Ecological
Hazard
and
Environmental
Risk
Assessment
for
Zinc
Omadine.
From
K.
Montague.
September
2004,
D309561
1.0
EXECUTIVE
SUMMARY
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1
2.0.
PHYSICAL
AND
CHEMICAL
PROPERTIES
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3.0
HAZARD
CHARACTERIZATION
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3.1
Hazard
Profile
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3.2
FQPA
Considerations
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17
3.3
Dose­
Response
Assessment
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18
3.4
Endocrine
Disruption
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19
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
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20
4.1
Summary
of
Registered
Uses
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20
4.2
Dietary
Exposure
and
Risk
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21
4.3
Drinking
Water
Exposure
and
Risk
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22
4.4
Residential
Exposure/
Risk
Pathway
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23
4.4.1
Residential
Handler
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23
4.4.2.
Anti­
Dandruff
Shampoo
Exposure
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26
4.4.3.
Postapplication
Residential
Exposure
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27
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
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29
5.1
Acute
Aggregate
Risk
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30
5.2
Short­
and
Intermediate­
Term
Aggregate
Risk
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32
5.3
Chronic
(
non­
cancer)
Aggregate
Risk
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34
6.0
CUMULATIVE
EXPOSURE
AND
RISK
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35
7.0
OCCUPATIONAL
EXPOSURE
AND
RISK
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36
8.0
INCIDENTS
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40
9.0
ENVIRONMENTAL
RISK
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40
10.0
DEFICIENCIES/
DATA
NEEDS
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47
11.0
REFERENCES
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48
1
1.0
EXECUTIVE
SUMMARY
Zinc
pyrithione
(
zinc
omadine
®
)
is
used
as
an
industrial
preservative
to
prevent
microbial
deterioration
and
to
maintain
the
integrity
of
manufacturing
precursor
materials
and
finished
manufactured
articles.
It
is
a
bacteriostat,
fungicide,
and
microbiocide/
microbiostat
registered
for
incorporation
into
food
packaging
adhesives
(
indoor
food),
incorporation
into
articles
made
from
or
coated
with
FDA
approved
food
contact
polymers
such
as
food
processing
equipment,
conveyor
belts,
utensils,
and
storage
containers
(
indoor
food),
paint
preservation
(
indoor/
outdoor
nonfood),
control
of
bacterial
growth
on
laundered
products
(
indoor
nonfood),
and
preservation
of
adhesives,
caulks,
patching
compounds,
sealants,
grouts,
latex
paints,
coatings,
dry
wall,
gypsum,
pearlite,
plaster
(
indoor
nonfood)
and
ductwork
(
HVAC
use).
Zinc
pyrithione
is
also
used
for
the
control
of
mildew
in
nonfood
contact
polymers
and
control
of
mildew
and
bacteria
in
styrene
butadiene
rubber
and
thermoplastic
resins
(
e.
g.
carpets
and
other
floor
coverings,
textiles,
home
furnishings,
housewares,
sports
equipment,
automotive/
public
transport
systems,
mattress
liners,
air
ducts,
etc).
In
addition,
it
is
conditionally
registered
as
an
antifouling
agent
for
boat
paints
to
control
the
growth
of
slime,
algae,
and
marine
fouling
organism
(
eg.,
barnacles,
tubeworms,
etc.)
below
the
water
line
of
recreational
and
commercial
boat
hulls
in
fresh,
salt,
or
brackish
water.
The
registrant,
Arch
Chemicals,
is
conducting
a
study
to
assess
exposures
of
workers
performing
painting
of
commercial
vessels
with
antifoulant
paints
containing
zinc
pyrithione.
This
study
is
expected
to
be
completed
and
submitted
in
2006,
and
will
be
used
to
assess
the
conditional
registrations
for
the
antifoulant
paint
use.
Ecological
risks
associated
with
antifoulant
paint
use
are
not
included
in
this
risk
assessment
because
of
pending
data,
and
will
be
assessed
upon
submission
of
the
requested
ecotoxicity
studies.
Residential
exposures,
however,
for
handlers
that
could
use
zinc
pyrithione­
containing
paint
on
recreational
boats
or
other
locations
are
assessed,
and
are
also
incorporated
into
the
aggregate
assessment.

In
addition
to
its
pesticidal
uses,
zinc
pyrithione
is
approved
by
the
Food
and
Drug
Administration
(
FDA)
for
use
in
anti­
dandruff
shampoos.
It
is
considered
to
be
safe
and
effective
(
considered
generally
recognized
as
safe
(
GRAS)
and
generally
recognized
as
effective
(
GRAE)
by
the
FDA
as
an
over
the
counter
drug)
for
the
treatment
of
dandruff
and
seborrheic
dermatitis
with
a
history
of
over
40
years
of
human
use.

Hazard:
The
toxicology
database
for
zinc
pyrithione
is
adequate
for
the
registered
uses,
but
uncertainty
factors
were
applied
for
lack
of
adequate
characterization
of
neurotoxicity
of
zinc
pyrithione.
Neurotoxicity
studies
are
requested
as
confirmatory
data
to
properly
characterize
the
dose­
response
relationship
that
exists
for
this
aspect
of
zinc
pyrithione
toxicity.

The
toxicology
database
for
zinc
pyrithione
indicates
that
by
the
oral
route,
zinc
pyrithione
is
moderately
toxic
(
LD
50
is
267
mg/
kg;
Toxicity
Category
II)
but
that
acute
toxicity
by
the
dermal
route
is
not
as
significant
(
LD
50
>
2000
mg/
kg;
Toxicity
Category
III).
Acute
toxicity
by
the
inhalation
route
is
also
relatively
low
(
LC
50>
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).
Zinc
pyrithione
does
not
demonstrate
dermal
sensitization
2
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
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
symptoms
similar
to
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.

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.
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
September
2003.

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
dose­
response
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
1
PAD
=
Population
Adjusted
Dose
=
Acute
or
Chronic
RfD
FQPA
Safety
Factor
3
effect
levels
as
other
adverse
responses,
the
doses
and
endpoints
selected
for
dietary
and
nondietary
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:
Because
zinc
pyrithione
causes
adverse
developmental
effects,
there
are
two
dermal
endpoints,
one
for
females
of
child
bearing
age
(
13­
50
years)
and
one
for
the
children.
The
short­
term,
intermediate­
term,
and
long­
term
dermal
endpoints
are
identical
for
these
two
population
subgroups.
The
dermal
endpoint
for
females
(
13­
50
years)
is
0.5
mg/
kg/
day
(
NOAEL)
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
dermal
endpoint
for
children
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.
A
3%
dermal
absorption
factor
is
used
for
the
dermal
endpoint
for
females
of
child
bearing
age.

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.

FQPA
Safety
Factor.
The
ADTC
committee
concluded
that
the
hazard
based
FQPA
safety
factor
can
be
reduced
to
1x
since
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)
1.
The
Agency
calculated
an
acute
PAD
and
a
chronic
PAD,
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
chronic
PAD
is
the
chronic
RfD
divided
by
the
FQPA
safety
factor.
4
Dietary
Exposure
and
Risk:
AD
considered
potential
dietary
exposure
to
zinc
pyrithione
residues
in
food
and
water.
When
assessing
acute
and
chronic
(
non­
cancer)
dietary
risk,
AD
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.
AD
expresses
dietary
risk
estimates
as
a
percentage
of
the
aPAD
or
chronic
PAD.
Dietary
exposures
that
are
less
than
100%
of
the
aPAD
or
cPAD
are
below
the
Agency's
level
of
concern.

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.
AD
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.

Chronic
Dietary
Risk.
In
the
present
submission,
without
further
data,
screening
level
estimates
used
for
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.

Water
Exposure
and
Risk:
AD
has
considered
the
conditionally
registered
use
of
zinc
pyrithione
in
antifoulant
paints
and
chemical­
specific
information
on
degradation,
mobility
and
leaching
rates
from
antifoulant
paint.
Uses
in
antifouling
paints
for
recreational
boats
are
expected
to
impact
surface
water
resources
(
i.
e.,
rivers,
lakes
and
marinas).
To
assess
drinking
water
impact,
the
Agency
estimated
predicted
environmental
concentrations
(
PEC)
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
(
100%
market
share
and
default
marina
values).
Because
of
lack
of
data
for
fresh
water,
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,
AD
considers
the
estimate
of
aggregate
risk
to
exceed
the
Agency's
level
of
concern.

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
objects,
rubber
gloves,
carpet
fibers,
synthetic
floor
coverings,
plastic
furniture,
mattress
liners/
ticking/
covers,
paints,
sealants
and
caulks.
The
Agency
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.
The
Agency
also
evaluated
potential
postapplication
exposures
to
consumer
products
that
contain
zinc
5
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
plastic
objects
(
i.
e.,
object
to
mouth),
and
incidental
ingestion
of
residues
on
hands
(
i.
e.,
hand
to
mouth)
from
contact
with
treated
plastic/
objects.
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
plastic
objects
via
object­
to­
mouth,
and
hand­
to­
mouth
exposures.
Residential
handler
exposure
scenarios
with
risk
estimates
that
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOEs
<
300)
are:

°
residential
handlers
that
paint
using
an
airless
sprayer:
(
antifoulant
paint
use:
dermal
MOEs=
15­
78,
inhalation
MOEs=
6­
33;
material
preservative
use
in
paints:
dermal
MOE=
117,
and
inhalation
MOE=
15;
°
residential
handlers
that
paint
using
a
brush:
(
antifoulant
paint
use
for
all
boat
sizes:
dermal
MOE=
3.2­
117;
inhalation
MOE=
18­
97
using
PHED
and
inhalation
MOE=
5­
140
using
Health
and
Safety
Executive
(
HSE)
data
(
Garrod
et
al.
2000);
material
preservative
use
in
paints
(
Dermal
MOE=
44);
and
°
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
the
dermal
risks
are
based
on
an
oral
developmental
study
and
a
3%
dermal
absorption
factor.
There
is
likely
reduced
bioavailability
of
zinc
pyrithione
from
dermal
contact
as
a
result
of
entrapment
in
a
paint
matrix.

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
long­
term
dermal
MOE
is
500,
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
6
shampoo
application
containing
radiolabeled
zinc
pyrithione.

Aggregate
Exposure
and
Risk:
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
Consequently,
even
though
no
pesticide
tolerances
have
been
established
for
zinc
pyrithione,
the
standards
of
FQPA
must
still
be
met.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
zinc
pyrithione.

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.
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.

Short
and
Intermediate
Term.
Short­
and
intermediate­
term
aggregate
risks
are
considered
together
since
the
exposure
and
toxicity
endpoints
are
identical
for
incidental
oral
residential
exposures
for
both
durations.
The
short­
and
intermediate­
term
aggregate
assessment
includes
average
dietary
exposure
(
food
and
water)
and
estimated
incidental
oral
exposures
from
residential
uses
such
as
plastic
objects
for
children.
For
adult
females,
the
aggregate
assessment
includes
dietary
(
oral)
and
residential
dermal
exposures
during
painting
since
there
is
concern
for
potential
developmental
effects
for
zinc
pyrithione.
Inhalation
residential
exposures
(
i.
e.,
residential
handler
during
painting
activities)
were
not
aggregated
with
the
oral
exposures
due
to
different
toxicological
endpoints
for
oral
(
increased
salivation/
developmental),
and
inhalation
(
clinical
signs
of
toxicity
and
lung
effects).

The
adult
aggregate
assessment
assumed
that
a
resident
would
apply
paint
containing
zinc
pyrithione
(
as
a
material
preservative)
via
an
aerosol
can
(
dermal
exposure),
in
addition
to
receiving
potential
oral
exposures
via
dietary
and
drinking
water
exposure.
As
noted
previously,
dermal
risks
are
already
of
concern
for
residents
that
could
apply
antifoulant
paint
to
their
boats
(
dermal
MOEs
range
from
3.2­
17
for
a
paintbrush,
and
15­
78
for
an
airless
sprayer),
or
use
a
paintbrush
or
an
airless
sprayer
to
apply
products
when
zinc
pyrithione
is
used
as
a
material
preservative
(
dermal
MOEs
are
44
and
17,
respectively).
Thus,
these
scenarios
were
not
considered
in
the
aggregate
risk
assessment,
because
inclusion
of
this
use
in
the
aggregate
would
also
contribute
to
dermal
aggregate
risks
of
concern.
7
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.

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).
For
adult
females,
this
assessment
includes
chronic
food
and
drinking
water
exposures,
in
addition
to
long­
term
residential
exposures
through
the
dermal
route
of
exposure
(
i.
e.,
anti­
dandruff
shampoo
use,
or
shoe
liner
exposure),
to
be
protective
of
potential
developmental
effects
of
zinc
pyrithione.
However,
for
children,
only
chronic
dietary
and
drinking
water
exposures
were
aggregated
because
the
developmental
effects
are
not
appropriate
for
assessing
children's
risk,
and
the
oral
and
dermal
endpoints
for
this
population
are
different.
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,
indicating
that
aggregate
food,
drinking
water
and
residential
(
as
appropriate)
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.

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
EPAregistered
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
a
time­
limited
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.

The
exposure
and
risk
assessment
for
primary
and
secondary
occupational
handlers
was
conducted
using
product
label
maximum
application
rates,
related
use
information
from
the
registrant
(
Arch
Chemicals,
Inc),
Agency
standard
values
for
industrial
practices,
and
unit
8
exposure
data
from
the
Chemical
Manufacturers
Association
(
CMA)
the
Pesticide
Handlers
Exposure
Database
(
PHED),
and
the
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
(
i.
e.,
target
MOEs

100)
below
the
Agency's
level
of
concern
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
of
concern
(
i.
e.,
MOEs
<
100):

°
mixing/
loading/
applying
powders
and
liquids
for
general
preservative
use
patterns
using
open
pour
methods
(
inhalation
MOE=
53
for
liquid
formulations;
inhalation
MOE=
15
for
powder
formulation;
dermal
MOE=
42
for
powder
formulation);
°
mixing/
loading/
applying
powders
and
liquids
for
paint
preservation
using
open
pour
methods
(
inhalation
MOE=
53
for
liquid
formulations;
inhalation
MOE=
15
for
powder
formulation;
dermal
MOE=
42
for
powder
formulation);
°
handling
zinc
pyrithione­
containing
paint
products
(
as
a
material
preservative)
using
an
airless
sprayer
application
method
(
inhalation
MOEs=
4.4
without
PPE,
and
44
with
the
use
of
an
organic
vapor
respirator
as
PPE,
and
dermal
MOE=
11
without
the
use
of
gloves
as
PPE,
and
MOE=
29
with
gloves),
and
°
handling
zinc
pyrithione­
containing
paint
products
(
as
a
material
preservative)
using
a
paintbrush
(
dermal
MOE=
22
without
gloves).

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
as
PPE
recommended
by
paint
manufacturers
for
spray
equipment
applications.
The
Agency
may
consider
requiring
risk
mitigation
steps,
such
as
closed
delivery
systems
or
use
of
a
respirator
during
open
pouring.
Although
the
dermal
MOE
for
a
paintbrush
scenario
is
of
concern
(
MOE=
22)
without
gloves,
the
MOE
is
not
of
concern
(
MOE=
167)
when
gloves
are
worn
as
protective
equipment.
It
is
assumed
that
in
real­
use
situations
the
occupational
handlers
will
have
adequate
dermal
protection
by
wearing
gloves
as
may
be
recommended
by
paint
manufacturers.
Dermal
and
inhalation
MOEs
obtained
for
the
painting
scenario
involving
use
of
an
aerosol
spray
can
application
method
is
not
of
risk
concern.

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.

Other
Food
Quality
Protection
Act
(
FQPA)
Considerations
9
Cumulative
Effects.
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
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.
Zinc
pyrithione
caused
impacts
on
growth
and
reproduction
to
several
species
of
aquatic
organisms
in
laboratory
studies,
at
levels
slightly
below
the
LC
50.
These
types
of
effects
suggest
that
zinc
pyrithione
may
possibly
have
endocrine
disruption
potential.
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
and
validated,
zinc
pyrithione
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

Environmental
Risk
Environmental
Fate.
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
hydrolytic
half­
lives
were
99,
120
and
123
days
at
pHs
5,
7
and
9,
respectively.
In
simulated
sea
water,
the
extrapolated
half
life
was
96
days.
Photolytic
measurements
showed
that
zinc
pyrithione
rapidly
degrades
with
a
half
life
of
13
minutes
in
buffered
medium
and
in
about
17
minutes
in
simulated
sea
water.
In
a
study
on
aerobic
10
aquatic
system,
zinc
pyrithione
degradation
follows
a
biphasic
process
and
in
the
first
phase
it
degrades
rapidly
with
a
half
life
of
0.065
hours
in
salt
water
and
in
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.
It
may
not
pose
a
concern
for
surface
water
run­
off.

There
are
multiple
degradation
pathways
for
zinc
pyrithione.
Under
aerobic
conditions,
zinc
pyrithione
degradation
half
life
is
0.6
hours
in
aqueous
system
and
0.89
days
in
sediment.
Similarly
zinc
pyrithione
shows
a
tendency
of
degrading
anaerobically
in
water
within
0.5
hours
and
in
about
19
hours
in
sediments.
It
may
not
be
a
concern
for
ground
water
contamination.

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.
There
may
be
a
short­
lived
water/
sediment
partitioning
issue.
There
could
be
an
acute
adverse
impact
on
benthic
aquatic
organisms.
However,
since
it
degrades
fairly
quickly
in
freshwater
and
saltwater
soils
and
sediments
(
half
lives
0.89
days
to
19
hours),
the
acute
adverse
impact
may
be
very
shortlived
It
is
not
likely
to
persist
in
water
and
microbial
soils
and
sediments.
Sediment
toxicity
studies
with
both
freshwater
and
marine
organisms
are
currently
in
progress
by
the
registrant.
The
results
of
these
studies
will
provide
additional
clarification
as
to
the
chemical
behavior
and
toxicity
of
zinc
pyrithione
in
water/
sediment
systems.

The
reported
Octanol/
Water
Partition
coefficient
K
OW
is
<
10
(
Log
Kow
is
0.97),
and
therefore
zinc
pyrithione
is
not
likely
to
bioaccumulate
in
aquatic
organisms
(
fish
etc.),
although
because
of
moderately
high
K
d
s
with
salt
water
sediments
it
may
partition
in
water
and
become
available
to
benthic
organisms.

Ecological
Hazard
and
Risk.
The
ecological
effects
database
for
zinc
pyrithione
is
adequate
to
support
the
indoor
uses
considered
in
this
report.
As
noted
previously,
the
antifoulant
paint
use
is
a
time­
limited
registration,
which
is
not
considered
in
this
document
for
ecological
risks,
but
will
be
re­
evaluated
upon
review
of
recently
submitted
ecotoxicity
studies.
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).
Zinc
pyrithione
is
very
highly
toxic
on
an
acute
basis
to
freshwater
and
marine
fish
and
invertebrates,
as
well
as
to
some
aquatic
plant
species.
It
also
caused
impacts
on
growth
and
reproduction
to
several
species
of
aquatic
organisms
in
laboratory
studies,
at
levels
slightly
below
the
LC
50.
These
types
of
effects
suggest
that
zinc
pyrithione
may
possibly
have
endocrine
disruption
potential
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
with
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
11
N+
O
S
N+
S
O
Zn
2­
and
invertebrates
and
aquatic
plants.

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.
The
ecological
risks
from
the
time­
limited
antifoulant
paint
use
will
be
evaluated
later,
following
a
review
of
the
recently
submitted
ecotoxicity
studies.

2.0.
PHYSICAL
AND
CHEMICAL
PROPERTIES
Identification
of
Active
Ingredients
Chemical
Name:
Zinc
pyrithione
Chemical
Name:
zinc
2­
pyridinethiol­
1­
oxide
Common
Name:
Zinc
Omadine
®
P.
C.
Code:
088002
CAS
Registry
Number:
13463­
41­
7
Empirical
Formula:
C
10
H
8
N
2
O
2
S
2
Zn
Molecular
Weight:
317.68
Vapor
Pressure:
1.87x10­
9
mmHg
Log
Kow
0.97
at
25o
C
Log
Koc
2.9­
4
Solubility
6
mg/
L
Structural
Formula:

Zinc
Pyrithione
appears
hydrolytically
stable
in
abiotic,
buffered
and
simulated
water
systems
with
an
extrapolated
half
life
between
99
and
123
days
in
buffered
medium
and
96
days
(
extrapolated)
in
simulated
sea
water.
Photolytically,
however,
it
rapidly
degrades
with
a
half
life
of
13
minutes
in
buffered
aqueous
medium
and
17
minutes
in
simulated
sea
water.
It
may
not
pose
a
concern
for
surface
water
runoff

There
are
multiple
degradation
pathways
for
zinc
pyrithione.
Under
aerobic
conditions,
zinc
pyrithione
degradation
half
life
is
0.6
hours
in
aqueous
system
and
0.89
days
in
sediment.
12
Similarly
zinc
pyrithione
shows
a
tendency
of
degrading
anaerobically
in
water
within
0.5
hours
and
in
about
19
hours
in
sediments.
It
may
not
be
a
concern
for
ground
water
contamination.

Zinc
pyrithione
shows
a
strong
tendency
(
large
K
d)
to
bind
with
fresh
water
and
salt
water
sediments.
It
is,
therefore,
not
a
mobile
pesticide
in
soils
and
sediments.
The
octanol/
water
partition
coefficient
is
less
than
10
(
Log
Kow
is
0.97),
which
makes
it
unlikely
to
bioaccumulate.

3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
A
detailed
hazard
assessment
for
zinc
pyrithione
is
presented
in
the
attached
memorandum
(
memo
from
T.
McMahon
to
N.
Cook,
April
2004).
The
acute
toxicity
of
zinc
pyrithione
is
low
for
dermal
toxicity
(
Toxicity
Category
III),
inhalation
toxicity
(
Toxicity
Category
III)
and
primary
dermal
irritation
(
Toxicity
Category
IV),
but
shows
higher
toxicity
for
acute
oral
toxicity
(
Toxicity
Category
II)
and
primary
eye
irritation
(
Toxicity
Category
I).
No
dermal
sensitization
was
observed
with
the
technical
test
material.
Table
1
presents
the
acute
toxicity
data
for
zinc
pyrithione.
Table
2
highlights
key
toxicological
studies
for
zinc
pyrithione
and
sodium
pyrithione.

Subchronic
Toxicity.
Subchronic
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
a
90­
day
whole­
body
inhalation
study,
rats
exhibited
clinical
signs
(
labored
breathing,
rales,
increased
salivation,
decreased
activity),
dry
red­
brown
stain
around
the
nose,
increased
absolute
and
relative
lung
weights
and
death
of
undetermined
cause
at
0.0025
mg/
L
(
0.65
mg/
kg/
day).
The
no­
observed­
adverse
effect
level
(
NOAEL)
was
0.0005
mg/
L
(
0.13
mg/
kg/
day).

Developmental
Toxicity.
In
both
oral
developmental
studies
in
rats
and
rabbits,
there
was
no
quantitative
evidence
of
increased
susceptibility
[
i.
e.,
maternal
and
developmental
noobserved
adverse
effect
levels
(
NOAELs)
were
the
same].
There
was
however,
qualitative
evidence
of
increased
susceptibility
(
i.
e.,
fetal
effects
were
considered
to
be
more
severe
in
the
presence
of
minimal
maternal
toxicity).
Neurotoxicity
in
maternal
animals
is
also
manifest
in
the
rat
developmental
study.
Data
on
neurotoxicity
in
developing
animals
are
lacking.

In
a
rat
developmental
study
(
MRID
42827904),
maternal
toxicity
was
evident
as
increased
salivation
at
3
mg/
kg/
day,
and
significant
decreases
in
body
weight
gains
and
food
consumption,
and
dilated
pupils
at
higher
doses.
Developmental
toxicity
was
characterized
by
a
dose
related
increase
in
postimplantation
loss
at
the
mid
and
high
doses,
which
was
statistically
significant
at
15
mg/
kg/
day.
This
correlated
with
an
increase
in
early
resorptions
with
whole
litter
13
resorption
occurring
in
3
high
dose
dams.
There
was
also
a
significant
reduction
in
the
number
of
live
fetuses
per
litter,
mean
fetal
weights,
and
gravid
uterine
weights
in
the
15
mg/
kg/
day
group.
A
significantly
greater
number
of
litters
in
the
15
mg/
kg/
day
group
contained
fetuses
with
external,
visceral,
or
skeletal
malformations/
variations.
The
most
common
were
digit
anomalies,
dilated
renal
pelvis,
which
is
considered
indicative
of
hydronephrosis,
a
vertebral/
rib
anomaly
and
sternal,
rib,
and
limb
(
radius
or
ulna
absent)
malformations.
Dose­
related
fused
ribs
were
observed
in
the
mid
and
high­
dose
groups
with
a
statistically
significant
linear
trend
and
exceedance
of
the
historical
control
values.
The
maternal
and
developmental
toxicity
NOAEL
is
0.75
mg/
kg/
day,
and
the
maternal
and
developmental
toxicity
LOAEL
is
3.0
mg/
kg/
day,
based
upon
excessive
salivation
in
dams
during
the
dosing
period
and
increased
incidences
of
fused
ribs.

In
a
developmental
toxicity
study
in
rabbits
(
MRID
#
42827905)
one
doe
had
total
litter
resorption
at
1.5
mg/
kg/
day,
while
at
3
mg/
kg/
day
one
high­
dose
doe
aborted
on
gestation
day
(
GD)
27,
and
five
others
had
total
resorptions.
Dose­
related
early
resorptions
were
seen
in
the
mid
and
high­
dose
does.
These
findings
corresponded
with
a
dose­
related
increase
in
postimplantation
loss
(
early
resorption)
and
a
decrease
in
viable
fetuses.
It
is
not
clear
whether
the
resorptions
were
due
to
maternal
or
developmental
toxicity.
No
statistically
significant
differences
were
seen
in
the
incidence
of
external,
visceral,
or
skeletal
anomalies
in
the
treated
groups
as
compared
to
controls.
Three
fetuses
from
two
high­
dose
litters
contained
multiple
cephalic
and
limb
malformations.
The
Maternal/
Developmental
NOAEL
is
0.5
mg/
kg/
day.
The
LOAEL
is
1.5
mg/
kg/
day,
based
on
increased
postimplantation
loss
and
decreased
number
of
viable
fetuses
(
it
is
not
clear
whether
the
resorptions
were
due
to
maternal
or
developmental
toxicity).

Reproductive
Toxicity.
Data
are
available
for
sodium
pyrithione
that
will
satisfy
the
data
requirement
for
zinc
pyrithione.
In
a
two
generation
reproduction
study
(
MRID
#
41097201)
conducted
with
40%
sodium
pyrithione,
parental/
systemic
toxicity
was
evidenced
as
skeletal
muscle
atrophy,
and
excessive
salivation
in
both
sexes
and
generations
of
parental
rats
at
the
1.5
and
3.5
mg/
kg/
day
dose
levels
and
decreased
body
weight
at
3.5
mg/
kg/
day.
Reproductive
toxicity
was
observed
at
the
3.5
mg/
kg/
day
dose
level
in
the
F0
parents
and
the
F1
offspring,
characterized
as
significantly
reduced
mating
and
fertility
index
in
males,
and
increased
number
of
estrous
cycles
per
mating
in
F0
females
at
3.5
mg/
kg/
day.
Mean
pup
body
weight
was
decreased
slightly
on
post­
natal
day
1
but
this
decrease
was
not
significant.
There
was
delayed
pup
development
at
3.5
mg/
kg/
day
as
indicated
by
decreases
in
developmental
landmarks
(
percentage
of
pups
with
ears
open
on
lactation
day
3
and
percentage
of
pups
with
eyes
open
on
lactation
day
15).
Mean
percentage
of
pups
with
startle
response
on
lactation
day
15
was
decreased
significantly
by
10%.
In
the
F1
parents
and
the
F2
offspring,
mating
and
fertility
indices
were
reduced
at
all
dose
levels
relative
to
control,
but
it
is
likely
that
atrophy
of
hindlimb
muscles
in
males
could
impact
mating
success
and
therefore
would
explain
the
decrease
in
mating
and
fertility
indices.
Mean
percentage
of
pups
with
startle
response
on
lactation
day
15
and
mean
percentage
of
pups
with
eyes
open
on
lactation
day
15
was
decreased
by
13%
and
14%
respectively,
but
this
was
not
statistically
significant.
14
Based
on
the
results
of
this
study,
the
systemic
NOAEL
and
LOAEL
are
0.5
mg/
kg/
day,
and
1.5
mg/
kg/
day,
respectively
based
on
increased
incidence
of
histological
alterations
of
the
hindlimb
skeletal
muscle
in
F0
males
and
F1
males
and
females.
The
reproductive
toxicity
NOAEL
and
LOAEL
are
1.5
mg/
kg/
day,
and
3.5
mg/
kg/
day,
respectively
based
on
slightly
decreased
number
of
pups
per
litter
in
both
generations,
delayed
development
in
pups
from
both
generations,
and
decreased
pup
body
weight
in
both
generations.

Chronic
Toxicity
and
Carcinogenicity.
Studies
with
zinc
pyrithione
were
not
available
to
satisfy
the
data
requirements
for
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
(
Tox
Record
003933,
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.

Genotoxicity.
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
positive
effect.
Therefore,
the
data
indicate
that
zinc
pyrithione
is
negative
for
mutagenic
effects.

Metabolism.
Disposition
and
metabolism
of
zinc
pyrithione
has
been
examined
in
older
studies
which
provide
incomplete
data.
Studies
from
the
published
literature
were
summarized,
but
not
reviewed
by
the
Agency.
In
Yorkshire
pigs
administered
an
intravenous
5
mg/
kg
dose
of
zinc
pyrithione,
plasma
elimination
was
described
as
biphasic,
with
a
t
½
alpha
of
2.0­
2.9
hr,
and
a
t
½
beta
of
26.6­
36.3
hr
(
Adams
et
al.
1976).
There
were
apparent
differences
in
urinary
elimination
of
14C
derived
radioactivity
from
administration
of
sodium
pyrithione
(
95%)
vs.
Zinc
pyrithione
(
45­
65%).
In
rabbits
administered
a
40
mg/
kg
oral
dose
of
zinc
pyrithione,
75%
of
the
administered
radioactivity
(
14C)
was
eliminated
in
urine
by
6
hours
post­
dose,
but
only
0.05%
of
zinc
was
eliminated
in
urine
(
Klaassen
1976).
Pharmacokinetic
studies
in
rats
showed
74­
84%
of
administered
oral
doses
of
0.5,
1.25,
and
12.5
mg/
kg
eliminated
in
urine
by
96
hours
post­
dose
(
Wedig
1978).
There
were
apparent
sex
differences
in
pharmacokinetics.
Klaasan
(
1976)
utilized
14C­
zinc
pyrithione
and
isotopic65­
zinc
pyrithione
to
study
zinc
pyrithione.
The
author's
conclusion
indicate
that
zinc
and
pyrithione
go
to
different
locations
in
the
body
and
are
eliminated
at
different
rates
and
different
routes.
The
data
do
suggest
less
in
vivo
dissociation
of
zinc
pyrithione
vs.
sodium
pyrithione
and
greater
retention
of
zinc
in
tissues
vs.
the
pyrithione
moiety.
15
Table
1.
Acute
Toxicity
of
Zinc
Pyrithione
Technical
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
870.1100
Acute
Oral­
Rats
42827901
LD50
=
267
mg/
kg
II
870.1200
Acute
Dermal­
Rats
42146701
LD50
>
2000
mg/
kg
III
870.1300
Acute
Inhalation­
Rats
42146703
LC50
>
0.61
mg/
L
III
870.2400
Primary
Eye
Irritation­
Rabbits
42146702
severe
irritant
I
870.2500
Primary
Skin
Irritation­
Rabbits
42146704
slight
erythema
and
edema
IV
870.2600
Dermal
Sensitization­
Guinea
pigs
43950201
no
sensitization
observed
using
Buehler
method
N/
A
870.6200
Neurotoxicity
screening
battery
non­
guideline
study
available 
progressive
hindlimb
weakness
and
muscle
atrophy
at
12.5
mg/
kg/
day
NA
Table
2.
Toxicity
Profile
of
Zinc
Pyrithione
Technical
Guideline
No./
Study
Type
Results
870.3250
90­
Day
dermal
toxicity
 
rat
Acceptable
Guideline
NOAEL
=
100
mg/
kg/
day
in
females
and
1000
mg/
kg/
day
in
males
LOAEL
=
1000
mg/
kg/
day
in
females
based
on
decreased
body
weight
gain,
food
consumption
and
food
efficiency.

870.3465
90­
Day
inhalation
toxicity
 
rat
Acceptable
Guideline
NOAEL
=
0.13
mg/
kg/
day
(
0.0005
mg/
L/
day)
LOAEL
=
0.65
mg/
kg/
day
(
0.0025
mg/
L/
day)
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.

870.3700a
Prenatal
developmental
in
rodents
 
rat
Acceptable
Guideline
Maternal
NOAEL
=
0.75
mg/
kg/
day
LOAEL
=
3
mg/
kg/
day
based
on
excessive
salivation
during
the
dosing
period.
Developmental
NOAEL
=
0.75
mg/
kg/
day
LOAEL
=
3
mg/
kg/
day
based
on
increased
incidences
of
fused
ribs.
Table
2.
Toxicity
Profile
of
Zinc
Pyrithione
Technical
Guideline
No./
Study
Type
Results
16
870.3700b
Prenatal
developmental
in
nonrodents
 
rabbit
Acceptable
Guideline
Maternal
NOAEL
=
0.5
mg/
kg/
day
LOAEL
=
1.5
mg/
kg/
day
based
on
increased
postimplantation
loss
and
decreased
number
of
viable
fetuses
(
it
is
unclear
whether
resorptions
were
due
to
maternal
or
developmental
toxicity)
Developmental
NOAEL
=
0.5
mg/
kg/
day
LOAEL
=
1.5
mg/
kg/
day
based
on
increased
postimplantation
loss
and
decreased
number
of
viable
fetuses.

870.3800
2­
Generation
Reproduction
and
fertility
effects
 
rat
Sodium
Pyrithione
Acceptable
Guideline
Parental/
Systemic
NOAEL
=
0.5
mg/
kg/
day
LOAEL
=
1.5
mg/
kg/
day
based
on
increased
incidence
of
histological
alterations
of
hindlimb
skeletal
muscle
in
F0
males
and
F1
males
and
females.
Reproductive
NOAEL
=
1.5
mg/
kg/
day
LOAEL
=
3.5
mg/
kg/
day
based
on
slightly
decreased
number
of
pups
per
litter
in
both
generations
Offspring
NOAEL
=
1.5
mg/
kg/
day
LOAEL
=
3.5
mg/
kg/
day
based
on
delayed
development
and
decreased
pup
body
weight
in
both
generations.

870.4300
Combined
Chronic
Toxicity/
Carcinogenicity
 
rat
(
gavage)
Sodium
Pyrithione
Acceptable
Guideline
NOAEL
=
0.5
mg/
kg/
day
LOAEL
=
1.5
mg/
kg/
day
based
on
increased
incidence
of
degeneration
of
skeletal
muscle
of
hindlimb
of
both
sexes.

Neurotoxicity.
No
recent
guideline
studies
have
been
submitted
to
the
Agency
with
respect
to
the
neurotoxicity
of
zinc
pyrithione.
In
a
non­
guideline
toxicity
study,
CD
male
rats,
150­
250g,
were
divided
into
63
pairs.
Technical
grade
zinc
pyrithione
(
97.0%)
was
administered
to
one
rat
of
each
pair
at
a
dose
of
250
ppm
for
either
9
or
14
days.
Gastrocnemius
and
soleus
muscles
were
examined
in
five
treated
and
five
pair­
fed
controls.
Eighteen
treated
and
18
pair­
fed
controls
were
used
for
ultrastructural
evaluation
of
nervous
tissue.
Nerve
conduction
velocity
of
the
sural
nerve
was
determined
in
a
total
of
74
treated
and
pair­
fed
controls.
In
vitro
recording
of
nerve
conduction
velocity
was
also
made
using
the
sciatic
nerve.
Histologic
morphology
of
all
examined
muscles
was
normal.
Sciatic,
sural,
and
spinal
nerve
roots
were
not
altered
after
14
days
of
treatment.
Myelinated
sural
nerve
axons
in
rats
recovered
for
2
weeks
showed
accumulation
of
dense
granular
axoplasmic
deposits.
The
most
prominent
changes
were
observed
in
intramuscular
lumbrical
fibers,
where
axons
were
enlarged
and
contained
abundant
mitochondria
and
electron
dense
granules.
Sensory
nerve
conduction
velocities
measured
in
vivo
showed
no
significant
difference
between
treated
and
control
rats.
However,
peak­
to­
peak
sensory
potential
amplitudes
were
significantly
different
between
treated
and
control
rats.
At
2
and
4
weeks
after
treatment,
clinical
signs
were
absent
in
treated
rats,
but
sensory
nerve
evoked
potential
amplitudes
remained
significantly
different
after
2
weeks
recovery.
The
results
of
this
study
suggest
a
primary
toxic
17
effect
of
zinc
pyrithione
on
muscle
fibers,
and
a
toxic
effect
on
nerve
fibers
consistent
with
random
axonal
loss
by
Wallerian
degeneration
or
inactivation.
i.
e.
approximately
5
mg/
kg
and
above.

Several
studies
published
in
the
open
scientific
literature
have
also
noted
neurotoxic
effects
from
exposure
to
zinc
pyrithione.
Ross
and
Lawhorn
(
1990)
observed
reduction
in
forelimb
and
hindlimb
grip
strength
and
electrophysiological
changes
after
administration
of
zinc
pyrithione
in
the
diet
at
50
ppm
(
2.5
mg/
kg/
day)
indicative
of
neurotoxicity
at
the
neuromuscular
junction.
Snyder
et
al.
(
1979)
observed
progressive
hind­
limb
weakness,
motor
incoordination,
and
reduced
sensory
and
mixed
sensory/
motor
nerve­
evoked
potential
amplitude
(
but
no
reduction
in
conduction
velocity)
in
male
rats
administered
250
ppm
(
12.5
mg/
kg/
day)
zinc
pyrithione
in
the
diet
for
9
or
14
days
with
a
4
week
recovery
period.
Although
clinical
signs
abated
during
the
recovery
period,
decreases
in
nerve­
evoked
potential
amplitude
remained
decreased.
Administration
of
zinc
pyrithione
to
dogs
has
produced
blindness
and
retinal
detachment
(
Grant,
1993).

3.2
FQPA
Considerations
Under
the
Food
Quality
Protection
Act
(
FQPA),
P.
L.
104­
170,
which
was
promulgated
in
1996
as
an
amendment
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
was
directed
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children"
from
aggregate
exposure
to
a
pesticide
chemical
residue.
The
law
further
states
that
in
the
case
of
threshold
effects,
for
purposes
of
providing
this
reasonable
certainty
of
no
harm,
"
an
additional
tenfold
margin
of
safety
for
the
pesticide
chemical
residue
and
other
sources
of
exposure
shall
be
applied
for
infants
and
children
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
data
with
respect
to
exposure
and
toxicity
to
infants
and
children.
Notwithstanding
such
requirement
for
an
additional
margin
of
safety,
the
Administrator
may
use
a
different
margin
of
safety
for
the
pesticide
residue
only
if,
on
the
basis
of
reliable
data,
such
margin
will
be
safe
for
infants
and
children."

The
HIARC
in
1999
recommended
retention
of
the
10x
safety
factor
for
the
protection
of
infants
and
children
based
on
qualitative
evidence
of
increased
susceptibility
in
the
rat
and
rabbit
prenatal
developmental
toxicity
studies,
the
lack
of
reproductive
toxicity
study
for
zinc
pyrithione
and
evidence
of
neurotoxicity
from
submitted
data
in
experimental
animals.
Since
that
time,
updated
guidance
on
interpretation
of
the
FQPA
safety
factor
http://
www.
epa.
gov/
oppfead1/
trac/
science/
determ.
pdf
)
has
been
published.
Based
on
this
updated
guidance
and
the
Antimicrobials
Division's
Toxicology
Endpoint
(
ADTC)
Selection
Committee,
reduced
the
special
hazard­
based
FQPA
safety
factor
to
1x.
This
reduction
was
based
on
the
following:

(
1)
the
developmental
toxicity
database
for
zinc
pyrithione
shows
effects
in
offspring
at
similar
dose
levels
as
effects
in
adults,
while
the
reproductive
toxicity
database
18
for
sodium
pyrithione
(
a
structurally
related
chemical)
shows
effects
in
offspring
at
doses
above
those
occurring
in
parental
animals.
(
2)
effects
observed
in
offspring
from
developmental
toxicity
studies
have
been
selected
for
use
in
dietary
risk
assessments,
thus
being
protective
of
infants
and
children.

Therefore
the
hazard
based
FQPA
safety
factor
can
be
reduced
to
1x
since
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.

3.3
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
below.

Table
3.
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
19
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,
Intermediateand
Long­
Term
Dermal
Adults
(
including
Females
13
­
50
years)
NOAEL
=
0.5
mg/
kg/
day
3%
dermal
absorption
Target
MOE
=
300
(
residential)
100
(
occupational)
Developmental
Toxicity
Study
in
Rabbits
LOAEL
=
1.5
mg/
kg/
day,
based
on
increased
post­
implantation
loss
and
decreased
viable
fetuses
Children
(
1­
6
yrs)
Dermal
NOAEL
=
100
mg/
kg/
day
dermal
absorption
factor
not
required
Target
MOE
=
300
(
residential)
90­
Day
Subchronic
Dermal
Toxicity
in
Rats
LOAEL
=
1000
mg/
kg/
day,
based
on
decreased
body
weight
gain,
food
consumption,
and
food
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.

Database
Uncertainty
Factor.
Based
on
the
need
for
additional
neurotoxicity
testing
and
evidence
of
neurotoxicity
in
the
open
scientific
literature
(
Ross
and
Lawhorn,
1990;
Snyder
et
al.,
1979;
Grant,
1993),
a
database
uncertainty
factor
of
3x
is
applied
to
non­
occupational
risk
assessments
for
zinc
pyrithione,
due
to
the
lack
of
characterization
of
neurotoxic
dose­
response
relationships
for
zinc
pyrithione.
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.

3.4
Endocrine
Disruption
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
20
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.

4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
Dietary
exposure
to
zinc
pyrithione
can
occur
from
use
in
food
packaging
adhesives,
food
packaging
materials,
conveyor
belts,
and
repeat
use
polymeric
food
contact
materials.
Residential
exposure
to
zinc
pyrithione
can
occur
from
zinc
pyrithione­
containing
products,
such
as
paint
(
as
a
materials
preservative),
or
caulk,
or
from
the
conditionally
registered
antifoulant
paint
use
on
recreational
boats.
Postapplication
exposure
can
occur
in
adults
and
children
from
dermal
contact
with
zinc
pyrithione­
treated
rubber/
plastic
articles,
as
well
as
in
children
from
object­
to­
mouth,
and
hand­
to­
mouth
incidental
oral
exposure.
Occupational
exposure
to
zinc
pyrithione
can
occur
from
mixing/
loading/
application
activities
in
the
industrial
setting,
including
manufacturing
antifoulant
paints
or
other
paint
products
and
from
subsequent
use
of
treated
paints,
coatings,
and
building
materials.

4.1
Summary
of
Registered
Uses
Zinc
pyrithione
(
Zinc
Omadine
®
,
or
Zinc
2­
pyridinethiol­
1­
oxide)
is
used
as
an
industrial
preservative
to
prevent
microbial
deterioration
and
to
maintain
the
integrity
of
manufacturing
precursor
materials
and
finished
manufactured
articles.
It
is
a
bacteriostat,
fungicide,
and
microbiocide/
microbiostat
registered
for
incorporation
into
food
packaging
adhesives
(
indoor
food),
incorporation
into
articles
made
from
or
coated
with
FDA
approved
food
contact
polymers
such
as
food
processing
equipment,
conveyor
belts,
utensils,
and
storage
containers
(
indoor
food),
paint
preservation
(
indoor/
outdoor
nonfood),
control
of
bacterial
growth
on
laundered
products
(
indoor
nonfood),
and
preservation
of
adhesives,
caulks,
patching
compounds,
sealants,
grouts,
latex
paints,
coatings,
dry
wall,
gypsum,
pearlite,
plaster
(
indoor
nonfood)
and
ductwork
(
HVAC
use).
Zinc
pyrithione
is
also
used
for
the
control
of
mildew
in
nonfood
contact
polymers
and
control
of
mildew
and
bacteria
in
styrene
butadiene
rubber
and
thermoplastic
resins
(
e.
g.
carpets
and
other
floor
coverings,
textiles,
home
furnishings,
housewares,
sports
equipment,
21
automotive/
public
transport
systems,
mattress
liners,
air
ducts,
etc.).
In
addition,
it
is
conditionally
registered
as
an
antifouling
agent
for
boat
paints
to
control
the
growth
of
slime,
algae,
and
marine
fouling
organism
(
eg.,
barnacles,
tubeworms,
etc.)
growth
below
the
water
line
of
recreational
and
commercial
boat
hulls
in
fresh,
salt,
or
brackish
water.

In
addition
to
its
pesticidal
uses,
zinc
pyrithione
is
approved
by
the
Food
and
Drug
Administration
(
FDA)
for
use
in
anti­
dandruff
shampoos.
It
is
considered
to
be
safe
and
effective
(
considered
generally
recognized
as
safe
(
GRAS)
and
generally
recognized
as
effective
(
GRAE)
by
the
FDA
as
an
over
the
counter
drug)
for
the
treatment
of
dandruff
and
seborrheic
dermatitis,
with
a
history
of
over
40
years
of
human
use.

4.2
Dietary
Exposure
and
Risk
Estimates
of
dietary
risk
are
based
upon
the
detailed
analysis
in
the
residue
chemistry
chapter
(
memo
from
N.
Shamim
to
J.
Fairfax,
D251938)
and
are
summarized
here
for
completeness.
FDA
has
approved
the
use
of
zinc
pyrithione
as
an
indirect
food
additive,
for
use
in
food
packaging
adhesives.
AD
used
the
FDA
recommended
migration
study
for
zinc
pyrithione
(
MRID#:
441086­
02)
to
determine
the
residues
in
food
and
to
calculate
acute
and
chronic
dietary
exposure
estimates.

The
label
provided
lists
the
following
repeat­
use
polymeric
food
contact
materials
for
zinc
pyrithione:
food
processing
equipment,
conveyer
belts,
utensils,
storage
containers
to
which
zinc
pyrithione
is
applied
to
control
the
growth
of
fungus.
AD
evaluated
conveyer
belts
as
representing
the
`
worst
case
scenario',
based
on
repeatability
of
use,
high
frequency
of
use
and
a
short
life
at
the
use
level.
Zinc
pyrithione
is
permitted
to
be
used
up
to
1000
ppm
in
food
packaging
and
polymeric
contact
surfaces
(
such
as
a
conveyor
belt).
The
Agency
has
estimated
that
approximately
0.7
ppm
zinc
pyrithione
migrates
in
food
simulating
solvents
(
50%
alcohol/
water),
and
that
0.6733
ppb/
day
migrates
from
the
conveyor
belt
to
food.
This
represents
the
maximum
leaching
observed
in
a
study,
and
was
considered
to
be
a
good
representative
of
all
food
packing/
containers.
Using
these
assumptions,
and
food
ingestion
rates
of
3000
g/
day
for
adults
and
1000
g/
day
for
children,
AD
estimated
daily
intakes
of
0.002
mg/
person/
day,
and
0.000673
mg/
person/
day
for
adults
and
children,
respectively.
These
daily
estimates
were
conservatively
used
to
assess
both
acute
and
chronic
dietary
risks,
which
are
shown
below
in
Table
4
The
risk
analysis
assumes
exposure
from
contact
with
polymeric
treated
articles
that
come
into
contact
with
food.
Food
storage
containers
are
not
included
in
the
chronic
dietary
exposure
analysis
as
migration
data
have
shown
that
maximum
migration
from
food
storage
containers
occurs
only
in
the
first
5
days,
which
constitutes
an
acute
but
not
chronic
dietary
exposure
scenario.
22
Table
4.
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
4.3
Drinking
Water
Exposure
and
Risk
AD
has
considered
the
conditionally
registered
use
of
zinc
pyrithione
in
antifoulant
paints
and
chemical­
specific
information
on
degradation,
mobility
and
leaching
rates
from
antifoulant
paint.
The
Agency
currently
lacks
sufficient
water­
related
exposure
data
from
monitoring
to
complete
a
quantitative
drinking
water
exposure
analysis
and
risk
assessment
for
zinc
pyrithione.
Therefore,
the
Agency
is
presently
relying
on
computer­
modeled
predicted
environmental
concentrations
(
PECs)
of
pesticides
in
water
to
estimate
drinking
water
exposures
to
zinc
pyrithione.
Details
of
the
water
exposure
estimates
are
present
in
the
attached
memorandum
(
memo
from
S.
Mostaghimi
to
D.
Smegal,
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,
April
2004).

Uses
in
antifouling
boat
paints
for
recreational
use
are
expected
to
impact
surface
water
resources
(
i.
e.,
lakes,
and
rivers)
that
could
serve
as
drinking
water
sources.
The
Agency
estimated
PECs
that
range
from
0.0144
to
0.101
ppb
zinc
pyrithione,
using
conservative
assumptions
and
the
Marine
Antifoulant
Model­
Predicted
Environmental
Concentration
(
MAMPEC
model
(
100%
market
share
and
default
marina
values).
MAM­
PEC
has
been
adopted
by
OECD,
and
predicts
total
concentrations
as
maximum,
95%,
average,
median
and
minimum
in
a
harbor.
A
range
of
average
PECs
were
estimated
based
on
three
different
leaching
rates
[
1.2
(
low),
4.8
(
average)
and
8.4
(
high)

g/
cm2/
day].
Because
of
the
lack
of
real
data
for
fresh
water,
the
PECs
estimated
by
MAM­
PEC
were
used
to
assess
potential
drinking
water
exposures
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.
The
primary
use
of
this
model
by
the
Agency
at
23
this
stage
is
to
provide
a
coarse
screen
for
assessing
whether
a
pesticide
is
likely
to
be
present
in
drinking
water
at
concentrations
that
would
exceed
the
human
health
levels
of
concern.

A
drinking
water
level
of
comparison
(
DWLOC)
is
the
concentration
of
a
pesticide
in
drinking
water
that
would
result
in
risk
estimates
below
AD's
level
of
concern,
when
considering
total
aggregate
exposure
to
that
pesticide
from
food,
water,
and
residential
uses.
AD
uses
DWLOCs
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
associated
with
pesticide
exposure
through
drinking
water.
DWLOC
values
are
not
regulatory
standards
for
drinking
water,
however,
they
do
have
an
indirect
regulatory
impact
through
aggregate
exposure
and
risk
assessment.
In
the
absences
of
monitoring
data
for
a
pesticide,
the
DWLOC
is
used
as
a
point
of
comparison
against
the
conservative
PEC
provided
by
computer
modeling.
A
DWLOC
may
vary
with
drinking
water
consumption
patterns
and
body
weight
for
specific
subpopulations.

AD
back­
calculates
DWLOCs
by
a
two­
step
process:
exposure
[
food
+
(
if
applicable)
residential
exposure]
is
subtracted
from
the
PAD
to
obtain
the
maximum
exposure
allowed
in
drinking
water;
DWLOCs
are
then
calculated
using
that
value
and
default
body
weight
and
drinking
water
consumption
figures.
In
assessing
human
health
risk,
DWLOCs
are
compared
to
the
PEC.
When
the
PEC
is
greater
than
the
DWLOCs,
AD
considers
the
aggregate
risk
[
from
food
+
water
(
if
applicable)
residential
exposure]
to
exceed
the
Agency's
level
of
concern.

4.4
Residential
Exposure/
Risk
Pathway
Details
of
the
residential
exposure
assessment
can
be
found
within
the
companion
memorandum
(
memorandum
from
D.
Aviado/
D.
Smegal,
April
2004).
A
summary
of
the
residential
assessment
is
presented
below.

4.4.1
Residential
Handler
Exposure
Scenarios
Zinc
Pyrithione
is
an
antifouling
agent
used
to
control
slime
and
algae
growth
below
the
water
line
of
recreational
and
commercial
boat
hulls
in
fresh,
salt,
or
brackish
water.
Recreational
boat
owners
have
several
techniques
they
can
use
to
paint
their
hulls
including
paint
brush,
roller,
and
airless
sprayer.
Residential
handler
exposures
could
also
occur
through
the
application
of
treated
paints
and
coatings,
and
building
materials
such
as
caulks,
adhesives,
spackling,
groutings,
sealants,
stucco
and
joint
cements.
The
following
residential
handler
scenarios
were
evaluated:

Antifoulant
Use:
(
1)
handling
zinc
pyrithione­
containing
antifoulant
paints
using
a
paint
brush.
(
2)
handling
zinc
pyrithione­
containing
antifoulant
paints
using
an
airless
sprayer.
Materials
Preservative
Use:
(
3,4,5)
handling
zinc
pyrithione­
containing
end­
products
using
paint
brush,
airless
sprayer,
and
aerosol
spray
can
application
methods.
24
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,
caulk
or
sealants.
Therefore,
residential
handler
exposures
were
assessed
for
the
application
of
paint,
as
this
scenario
represents
maximum
possible
exposure
to
the
chemical.

Exposure
Data
and
Assumptions
There
are
no
chemical­
specific
exposure
data
to
assess
paint
applications
with
a
brush,
roller,
airless
sprayer
or
aerosol
can.
However,
surrogate
data
are
available
for
painting
with
a
brush,
an
airless
sprayer
and
aerosol
can.
Dermal
and
inhalation
exposures
were
assessed
for
brush,
airless
sprayer,
and
aerosol
application
methods
using
PHED
Version
1.1
values
found
in
the
Residential
Exposure
SOPs
(
U.
S.
EPA,
1997a,
2001).
The
surrogate
exposure
data
in
PHED
are
based
on
test
subjects
painting
a
bathroom
with
a
paint
brush
and
staining
the
outside
of
a
house
with
an
airless
sprayer.
The
dermal
and
inhalation
exposures
from
these
techniques
have
been
normalized
by
the
amount
of
active
ingredient
handled
and
reported
as
unit
exposures
(
UE)
expressed
as
mg/
lb
ai
handled.
Although
the
exposures
while
painting
a
boat
hull
may
differ
slightly,
the
data
are
judged
to
be
representative
of
painting
and
are
used
in
this
assessment.
The
data
from
Garrod
et
al.
(
2000),
which
evaluated
amateur
(
consumer)
applicators
applying
antifoulant
paint
using
a
paint
brush
and
roller
to
boat
hulls
of
recreational
craft
stored
on
sling/
cradle/
trailers,
were
also
used
as
a
comparison
to
PHED.
The
Garrod
(
2000)
study
design
is
more
representative
of
the
use
(
i.
e.,
painting
boat
hulls
using
an
antifoulant
paint).
The
air
concentration
data
from
Garrod
et
al.
(
2000)
are
used
to
present
the
inhalation
route­
specific
risks
in
normalized
units
of
mg/
m3.
The
dermal
portion
of
the
study
monitored
mostly
exposure
on
the
outside
of
clothing
and
only
one
patch
was
used
underneath
clothing,
and
thus
these
data
are
not
of
sufficient
quality
for
a
dermal
risk
assessment.
In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
residential
handler
exposures.

Risk
Characterization
A
summary
of
the
residential
handler
exposures
and
risk
are
presented
on
Table
5.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
MOEs

300
do
not
exceed
the
Agency's
level
of
concern
for
residents.
MOEs
from
residential
use
of
zinc
pyrithione­
containing
antifoulant
boat
paint
on
recreational
boats
showed
that
dermal
and
inhalation
MOEs
were
of
concern
(
i.
e.
<
300)
for
all
boat
sizes
when
using
a
paint
brush
and
airless
sprayer.
It
is
important
to
note
that
the
inhalation
risk
estimates
are
conservative
because
the
toxicity
endpoint
is
based
on
a
whole­
body
rat
90­
day
inhalation
study.

For
residential
handlers
that
handle
products
containing
zinc
pyrithione
as
a
materials
preservative,
short­
term,
intermediate­
term,
and
long­
term
MOEs
exceed
the
Agency's
level
of
concern
(
MOEs
<
300)
for
the
following
scenarios:

°
handling
zinc
pyrithione­
containing
paint
products
using
an
airless
sprayer
25
application
method
(
Dermal
MOE=
17
and
inhalation
MOE=
15);
°
handling
zinc
pyrithione­
containing
paint
products
using
a
paintbrush
(
Dermal
MOE=
44);
and
°
handling
zinc
pyrithione­
containing
paint
products
using
an
aerosol
spray
can
application
method
(
inhalation
MOE=
271).

Dermal
MOEs
were
not
of
concern
for
the
painting
scenarios
involving
use
of
an
aerosol
spray
can
for
the
materials
preservative
use
of
zinc
pyrithione.

Table
5
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
MOEd
Acceptable
MOE

300
Inhalation
MOEe
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
assuming
dilution
to
5.8%
ai)]
All
Estimates
Based
on
3
Coats
of
Paint
in
One
Day
(
1a)
Brush
f
(
PHED)
0.03­
0.16
0.0071­
0.0013
3.2­
17
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
0.033­
0.0063
0.021­
0.004
15­
78
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
0.0115
4.0E­
4
44
325
(
4)
Handling
zinc
pyrithione­
containing
paint
end
products
using
an
airless
sprayer
application
method
0.0296
8.89E­
3
17
15
(
5)
Handling
zinc
pyrithione­
containing
paint
end
products
using
an
aerosol
spray
can
application
method
0.0015
4.80E­
4
325
271
Footnotes:
a
Scenarios
based
on
use
patterns
described
on
labels
and
LUIS
report.
Residential
handlers
include
homeowners
who
apply
products
containing
zinc
pyrithione
incorporated
as
a
general
preservative
(
e.
g.,
floor
tile
adhesives,
caulks/
sealants,
grout/
patching
materials,
and
rubber/
thermoplastic
resin/
polymericbased
products),
and
homeowners
who
apply
latex
paint,
architectural
coating,
and
dry
wall
and
building
materials
that
contain
zinc
pyrithione.
26
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)*
0.03
(
dermal
absorption
factor)]
/
Body
Weight
(
kg).
*
Use
of
gloves
as
PPE
assumes
a
90%
protection
factor.
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
NOAEL
is
0.5
mg/
kg/
day
from
the
rabbit
developmental
study.
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.

4.4.2.
Anti­
Dandruff
Shampoo
Exposure
Zinc
pyrithione
is
approved
by
the
Food
and
Drug
Administration
(
FDA)
for
use
in
antidandruff
shampoos.
It
is
considered
to
be
safe
and
effective
[
considered
generally
recognized
as
safe
(
GRAS)
and
generally
recognized
as
effective
(
GRAE)
by
the
FDA
as
an
over
the
counter
drug]
for
the
treatment
of
dandruff
and
seborrheic
dermatitis
with
a
history
of
over
40
years
of
human
use.
It
can
be
purchased
as
an
over­
the­
counter
product
that
does
not
require
a
prescription.
It
is
present
at
concentrations
ranging
from
0.3
to
2
percent
when
formulated
to
be
applied
and
then
washed
off
after
brief
exposures,
and
from
0.1
to
0.25
percent
when
formulated
to
be
applied
and
then
left
on
the
skin
or
scalp
(
21
CFR
§
358.710).

Percutaneous
absorption
of
zinc
pyrithione
was
assessed
for
anti­
dandruff
shampoo
use
for
adults.
It
was
assumed
that
infants
and
small
children
do
not
use
anti­
dandruff
shampoo
on
a
regular
basis.
Information
on
the
absorption
of
zinc
pyrithione
from
the
use
of
anti­
dandruff
shampoos
was
obtained
from
the
FDA's
docket
supporting
formal
rulemaking
leading
to
a
monograph
establishing
conditions
under
which
over­
the­
counter
drug
products
for
the
control
of
dandruff,
seborrheic
dermatitis
and
psoriasis
are
generally
recognized
as
safe
and
effective.
In
a
study
involving
30
human
subjects,
a
shampoo
containing
radio
labeled
zinc
pyrithione
(
14C
in
the
2­
and
6­
positions)
was
applied
in
both
a
sink
shampoo
procedure
(
head
exposure
only)
and
a
shower
shampoo
(
total
body
exposure)
(
Barker
and
Winrow
1979).
All
wash
water
and
towels,
etc.
were
retained
and
biological
samples
of
skin,
hair,
blood
and
urine
collected
for
a
period
of
ten
days
following
application.
Recovery
of
radio
label
was
essentially
100%.
In
this
study,
the
maximum
amount
of
zinc
pyrithione
in
the
urine
was
50

g,
which
is
equivalent
to
an
average
upper
systemic
load
(
absorbed
dose)
of
0.001
mg/
kg/
day
zinc
pyrithione.
In
this
study,
absorption
was
greatest
for
subjects
with
seborrheic
dermatitis,
and
the
absorbed
material
was
derived
from
solid
zinc
pyrithione
deposited
on
the
head.

In
this
assessment,
is
was
conservatively
assumed
that
a
50
kg
person,
has
chronic
27
seborrheic
dermatitis
and
uses
an
anti­
dandruff
shampoo
every
day,
absorbing
the
maximum
dose
of
the
active
ingredient.
Table
6
presents
a
summary
of
the
exposure
and
risks
(
MOEs)
for
the
anti­
dandruff
shampoo.

Table
6:
Summary
of
Long­
Term
Exposure
and
Risk
for
Anti­
Dandruff
Shampoo
Scenario
Receptor
Use
Potential
Absorbed
Dosea
(
mg/
kg/
day)
Dermal
MOEb
Target
MOE

300
Dermal
Contact
(
percutaneous
absorption)
Adult
Treatment
of
dandruff
and
seborrheic
dermatitis
0.001
500
a
An
absorbed
dose
of
0.001
mg/
kg/
day.
b
MOE=
NOAEL
(
mg/
kg/
day)
/
PDR
(
mg/
kg/
day).
NOAEL
is
0.5
mg/
kg/
day
for
developmental
effects
from
an
oral
developmental
toxicity
study.
The
dermal
absorption
of
zinc
pyrithione
is
approximately
3%,
however,
no
adjustment
for
dermal
absorption
is
necessary
because
the
exposure
estimate
is
an
"
absorbed
dose"
based
on
urinary
excretion
of
zinc
pyrithione.

4.4.3.
Postapplication
Residential
Exposure
Residential
postapplication
exposures
result
when
bystanders
(
adults
and
children)
come
in
contact
with
zinc
pyrithione
in
areas
where
pesticide­
treated
end­
use
products
have
recently
been
applied
(
e.
g.,
freshly
painted
walls
or
boat
hulls
of
recreational
craft),
or
when
children
incidentally
ingest
the
pesticide
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
handto
mouth
or
object­
to­
mouth
contact).

Zinc
pyrithione
is
used
as
a
microbiostat
and
mildewcide
to
control
bacterial
and
mildew
growth
in
articles
used
as
components
of
heating
ventilation
and
air
conditioning
(
HVAC)
systems.
Zinc
pyrithione
is
impregnated
into
thermoplastic
resins
at
concentrations
up
to
4000
ppm.
These
thermoplastic
resins
can
be
incorporated
into
air
filters,
air
filtration
components,
air
filtration
media,
and
duct
work.
These
end
use
products
are
intended
for
industrial,
hospital,
residential
and
commercial
HVAC
systems.

Although
EPA­
registered
zinc
pyrithione
pesticide
product
concentrates
are
not
used
in
residential
areas,
the
manufactured
consumer
end­
products
containing
zinc
pyrithione
are
used
extensively
in
and
around
the
home.
Based
on
the
use
patterns,
EPA
has
identified
exposure
scenarios
for
assessing
residential
postapplication
exposures
including:

°
Dermal
exposures
to
consumers
from
products
made
of
polymeric
materials
containing
zinc
pyrithione,
such
as
shoe
sole
liners;
28
°
Non­
dietary
ingestion
exposures
to
children
associated
with
object­
to­
mouth
contact
with
zinc
pyrithione­
treated
polymeric
products
(
i.
e.,
plastic
objects);
and
°
Non­
dietary
ingestion
exposures
to
children
associated
with
hand­
to­
mouth
contact
with
zinc
pyrithione­
treated
polymeric
products
(
i.
e.,
plastic
objects).

A
summary
of
the
residential
postapplication
exposures
and
risk
are
presented
on
Table
7.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
MOEs

300
do
not
exceed
the
Agency's
level
of
concern
for
residents.
Dermal
exposures
to
plastic
treated
with
zinc
pyrithione,
such
as
shoe
liners,
were
evaluated
and
determined
not
to
be
of
concern
(
MOEs
range
from
4,500­
7,700).
In
addition,
non­
dietary
incidental
ingestion
exposures
of
children
via
objectto
mouth
and
hand­
to­
mouth
activities
did
not
exceed
the
Agency's
level
of
concern
(
MOE
>
300).
Aggregate
postapplication
residential
exposures
for
a
young
child
were
also
greater
than
the
target
MOE
of
300,
and
are
not
of
concern.
As
noted
previously,
dermal
and
incidental
oral
exposures
and
risks
are
not
aggregated
because
the
toxicological
endpoints
are
different
for
dermal
(
decreased
body
weight
gain,
food
consumption
and
food
efficiency)
and
oral
(
increased
salivation)
exposures.

Postapplication
residential
dermal
exposures
are
expected
to
be
of
minimal
concern
for
treated
articles
used
in
HVAC
systems
since
these
components
are
not
readily
available
for
dermal
contact.
Dermal
contact
with
wet
paint
was
not
assessed
because
the
paint
is
expected
to
dry
within
a
day,
so
any
potential
exposure
is
expected
to
be
negligible.
The
potential
postapplication
inhalation
exposure
from
zinc
pyrithione
treated
articles,
such
as
air
duct
surfaces
in
HVAC
systems,
is
expected
to
be
minimal
based
on
bounding
estimates
of
saturation
concentrations
and/
or
dry
aerosols
from
particles
degraded
from
air
duct
surfaces.
Zinc
pyrithione
has
a
low
vapor
pressure
(
i.
e.,
1.87x10­
9
mmHg
@
25

C)
and
is,
therefore,
not
likely
to
generate
sufficient
vapor
to
cause
an
inhalation
concern
to
residential
populations
performing
postapplication
tasks,
or
occupying
recently
treated
areas,
or
from
bystander
contact
with
treated
articles.
Thus,
there
are
no
risk
concerns
and
inhalation
postapplication
exposures
were
not
quantitatively
evaluated.

Table
7.
Summary
of
Short­,
and
Intermediate­
Term
Residential
Postapplication
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)
4.06E­
4
1,231
NA
Toddlers
2.2E­
2
4,500
NA
Non­
Dietary
Ingestion
Object­
to­
Mouth
Infants
Rubber/
Plastic
0.0004
NA
2,000
Table
7.
Summary
of
Short­,
and
Intermediate­
Term
Residential
Postapplication
Exposure
and
Risks
(
c)

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

300
Oral
MOEb
Target
MOE

300
29
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
4.06E­
4
(
dermal)
1,231
NA
NA
=
Not
applicable.
a
Potential
dose
calculations
for
each
scenario
above
are
outlined
in
the
attached
Occupational/
Residential
Assessment
(
memo
from
D.
Aviado/
D.
Smegal,
September
2004).
b
MOE=
NOAEL
(
mg/
kg/
day)
/
PDR
(
mg/
kg/
day).
Dermal
NOAEL
is
100
mg/
kg/
day
for
children
and
0.5
mg/
kg/
day
for
adults
to
be
protective
of
potential
developmental
effects;
oral
NOAEL
is
0.75
mg/
kg/
day
for
children.
c
Dermal
risks
are
also
for
long­
term
exposures.

5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
Consequently,
even
though
no
pesticide
tolerances
have
been
established
for
zinc
pyrithione,
the
standards
of
FQPA
must
still
be
met,
including
"
that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).
Aggregate
risk
assessment
were
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
several
months
to
lifetime)
exposures.
As
noted
previously,
dermal
and
oral
exposures
were
only
combined
in
the
aggregate
assessment
for
adult
females
to
be
protective
of
potential
developmental
effects
of
zinc
pyrithione.
However,
for
children,
oral
and
dermal
exposures
were
not
combined
because
of
different
30
toxicological
endpoints
for
children.

In
performing
aggregate
exposure
and
risk
assessments,
the
Office
of
Pesticide
Programs
has
published
guidance
outlining
the
necessary
steps
to
perform
such
assessments
(
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments,
November
28,
2001;
available
at
http://
www.
epa.
gov/
pesticides/
trac/
science/
aggregate.
pdf
).
Steps
for
deciding
whether
to
perform
aggregate
exposure
and
risk
assessments
are
listed,
which
include:
identification
of
toxicological
endpoints
for
each
exposure
route
and
duration;
identification
of
potential
exposures
for
each
pathway
(
food,
water,
and/
or
residential);
reconciliation
of
durations
and
pathways
of
exposure
with
durations
and
pathways
of
health
effects;
determination
of
which
possible
residential
exposure
scenarios
are
likely
to
occur
together
within
a
given
time
frame;
determination
of
magnitude
and
duration
of
exposure
for
all
exposure
combinations;
determination
of
the
appropriate
technique
(
deterministic
or
probabilistic)
for
exposure
assessment;
and
determination
of
the
appropriate
risk
metric
to
estimate
aggregate
risk.
Aggregate
short
and
intermediate
term
risk
assessments
are
designed
to
provide
estimates
of
risk
likely
to
result
from
exposures
to
the
pesticide
or
pesticide
residues
in
food,
water,
and
from
residential
(
or
other
non­
occupational)
pesticide
uses.
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
nondietary
exposures.

5.1
Acute
Aggregate
Risk
5.1.1
Acute
Aggregate
Risk
Assessment
The
acute
aggregate
assessment
includes
both
dietary
and
drinking
water
exposures.
The
acute
dietary
risk
estimates
from
indirect
food
uses
(
i.
e.
use
in
food­
contact
packaging
and
treated
articles)
range
from
1.1­
2.7%
of
the
aPAD,
with
infants/
children
being
the
highest
exposed
population
subgroup.
Thus,
the
acute
dietary
(
food)
risk
estimate
associated
with
zinc
pyrithione
is
below
the
Agency's
level
of
concern.
Drinking
water
exposure
is
not
expected
from
the
indoor
uses
of
zinc
pyrithione,
but
could
occur
from
the
conditionally
registered
antifoulant
paint
use.
Drinking
water
monitoring
data
are
not
available,
therefore,
AD
calculated
drinking
water
level
of
comparisons
(
DWLOCs),
which
are
discussed
below
to
account
for
potential
drinking
water
exposures.

5.1.2
Acute
DWLOC
Calculations
A
drinking
water
level
of
comparison
(
DWLOC)
is
the
concentration
of
a
pesticide
in
drinking
water
that
would
result
in
risk
estimates
below
AD's
level
of
concern,
when
considering
total
aggregate
exposure
to
that
pesticide
from
food,
drinking
water,
and
residential
uses.
AD
uses
the
DWLOCs
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
associated
with
pesticide
exposure
through
drinking
water.
In
the
absence
of
monitoring
data
for
a
pesticide,
the
DWLOC
is
used
as
a
point
of
comparison
against
the
conservative
predicted
31
environmental
concentrations
(
PECs)
provided
by
computer
modeling.

AD
back­
calculates
the
acute
DWLOCs
by
a
two­
step
process:
exposure
[
food+
(
if
applicable)
residential
exposure]
is
subtracted
from
the
acute
PAD
to
obtain
the
maximum
exposure
allowed
in
drinking
water;
DWLOCs
are
then
calculated
using
that
value
and
default
body
weight
and
drinking
water
consumption
values.
A
DWLOC
may
vary
depending
on
the
toxic
endpoint,
drinking
water
consumption
patterns,
and
body
weights
for
specific
subpopulations.
In
assessing
human
health
risk,
the
acute
DWLOCs
are
compared
to
the
(
maximum)
PECs.
When
PECs
are
greater
than
DWLOCs
AD
considers
the
aggregate
risk
estimates
[
from
food
+
water
+
(
if
applicable)
residential
exposures]
to
exceed
the
Agency's
level
of
concern
(
HED
SOP
99.5
"
Standard
Operating
Procedures
for
Incorporating
Estimates
of
Drinking
Water
Exposure
into
Aggregate
Risk
Assessment,
August
1,
1999).

Table
8
presents
the
total
acute
dietary
exposure
estimate
for
zinc
pyrithione,
and
the
acute
DWLOCs.
For
each
population
subgroup
listed,
the
acute
PAD
and
the
acute
dietary
(
food)
exposure
(
from
Table
4)
for
that
subgroup
were
used
to
calculate
the
acute
DWLOC,
using
the
formulas
in
the
footnotes
of
Table
8.

Using
a
conservative
screening­
level
model,
the
range
of
average
PECs
for
zinc
pyrithione
in
a
marina
is
0.0144
to
0.101
ppb.
As
shown
on
Table
8,
the
acute
DWLOCs
are
greater
than
the
range
of
PECs,
indicating
that
aggregate
food
and
drinking
water
exposure
do
not
exceed
the
Agency's
level
of
concern.

Table
8.
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
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)]
[
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?
32
5.2
Short­
and
Intermediate­
Term
Aggregate
Risk
Short­
and
intermediate­
term
aggregate
risks
are
considered
together
since
the
exposure
and
toxicity
endpoints
are
identical
for
incidental
oral
residential
exposures
for
both
durations.
The
short­
and
intermediate­
term
aggregate
assessment
includes
average
dietary
exposure
(
food
and
water)
and
estimated
incidental
oral
exposures
from
residential
uses
such
as
plastic
objects
for
children.
For
adult
females,
the
aggregate
assessment
includes
dietary
(
oral)
and
residential
dermal
exposures
during
painting
since
there
is
concern
for
potential
developmental
effects
for
zinc
pyrithione.
Inhalation
residential
exposures
(
i.
e.,
residential
handler
during
painting
activities)
were
not
aggregated
with
the
oral
exposures
due
to
different
toxicological
endpoints
for
oral
(
increased
salivation/
developmental),
and
inhalation
(
clinical
signs
of
toxicity
and
lung
effects).

Aggregate
risks
were
calculated
using
the
total
MOE
approach
outlined
in
OPP
guidance
for
aggregate
risk
assessment
(
August
1,
1999,
Updated
"
Interim
Guidance
for
Incorporating
Drinking
Water
Exposure
into
Aggregate
Risk
Assessments").
The
assumptions
and
equations
are
presented
in
the
footnotes
on
Table
9.

Table
9
presents
a
summary
of
the
short­
and
intermediate­
term
aggregate
risk
and
DWLOCs.
The
DWLOCs
are
greater
than
the
PECs
for
adult
females
and
children,
indicating
that
aggregate
risks
do
not
exceed
the
Agency's
level
of
concern
for
these
subpopulation
groups.
It
should
be
noted
that
several
conservative
assumptions
were
used
in
this
assessment.

The
adult
aggregate
assessment
assumed
that
a
resident
would
apply
paint
containing
zinc
pyrithione
(
as
a
material
preservative)
via
an
aerosol
can
(
dermal
exposure),
in
addition
to
receiving
potential
oral
exposures
via
dietary
and
drinking
water
exposure.
As
noted
previously
(
and
shown
on
Table
5),
dermal
risks
are
already
of
concern
for
residents
that
could
apply
antifoulant
paint
to
their
boats
(
dermal
MOEs
range
from
3.2­
17
for
a
paintbrush,
and
15­
78
for
an
airless
sprayer),
or
use
a
paintbrush
or
an
airless
sprayer
to
apply
products
when
zinc
pyrithione
is
used
as
a
material
preservative
(
dermal
MOEs
are
44
and
17,
respectively).
Thus,
these
scenarios
were
not
considered
in
the
aggregate
risk
assessment,
because
inclusion
of
this
use
in
the
aggregate
would
also
contribute
to
dermal
aggregate
risks
of
concern.

Inhalation
Aggregate
Risk
Results.
An
inhalation
aggregate
assessment
was
not
conducted.
However,
as
shown
previously
on
Table
5,
short­
and
intermediate
inhalation
MOEs
for
residential
handlers
that
could
apply
antifoulant
paint
to
their
boats,
or
apply
products
containing
zinc
pyrithione
as
a
material
preservative
using
an
airless
sprayer
and
aerosol
can
exceed
the
Agency's
level
of
concern
(
inhalation
MOEs
range
from
6­
271
for
a
paintbrush,
airless
sprayer,
and
aerosol
can).
However,
it
is
important
to
note
that
these
risk
estimates
are
conservative
because
the
toxicity
endpoint
is
based
on
a
whole­
body
rat
90­
day
inhalation
study.
33
Table
9
Summary
of
Short­
and
Intermediate­
Term
(
ST/
IT)
Aggregate
Exposure
and
DWLOC
Calculations
Population
Subgroup
ST/
IT
NOAEL
(
mg/
kg/
day)/

Target
MOE
Chronic
Food
Exp
mg/
kg/
day/

(
MOE)
ST/
IT
Residential
Exposure
(
mg/
kg/
day)/

(
MOE)
5
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
Adults
(
Females
13­
50
years)
0.75/
300
0.000033/

(
22727)
0.0015
/(
500)

(
dermal)
775
0.00096
0.0144­
0.101
29
No
Infants/
Children
0.000067/

(
11195)
0.0007/

(
1100)
(
oral)
428
0.0017
17
No
ST=
short­
term;
IT=
intermediate
term
1
MOE
water
=
1
/
[
1/
MOE
target
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
60
kg
and
10
kg
for
adult
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
Residential
exposure
based
on
total
oral
exposure
for
infants/
children
on
Table
7
for
zinc
pyrithione
treated
objects.
Adult
exposure
based
on
dermal
exposure
from
painting
using
an
aerosol
can
on
Table
5.

6
Short­
term
oral
NOAEL
(
0.75
mg/
kg/
day)
/
MOE
water.
34
5.3
Chronic
(
non­
cancer)
Aggregate
Risk
5.3.1
Aggregate
Chronic
(
non­
cancer)
Risk
Assessment
The
chronic
aggregate
assessment
for
adult
females
includes
dietary,
residential
and
drinking
water
exposures.
The
chronic
dietary
risk
estimates
from
indirect
food
uses
(
i.
e.
use
in
food­
contact
packaging
and
treated
articles)
range
from
1.8­
4.2%
of
the
cPAD,
with
infants/
children
being
the
highest
exposed
population
subgroup.
Thus,
the
chronic
dietary
(
food)
risk
estimate
associated
with
zinc
pyrithione
is
below
the
Agency's
level
of
concern.
Drinking
water
exposure
is
not
expected
from
the
indoor
uses
of
zinc
pyrithione,
but
could
occur
from
the
antifoulant
paint
use.
Drinking
water
monitoring
data
are
not
available,
therefore,
AD
calculated
DWLOCs,
which
are
discussed
below
to
account
for
potential
drinking
water
exposures.

The
chronic
aggregate
risk
estimate
for
adult
females
considers
the
long­
term
dermal
residential
exposures
(
i.
e.,
contact
with
shoe
liners,
and
anti­
dandruff
shampoo),
in
order
to
be
protective
of
potential
developmental
effects
that
could
occur
via
oral
and
dermal
exposures.
However,
for
children,
it
is
not
appropriate
to
aggregate
dermal
exposures
from
a
shoe
liner
with
oral
exposures
because
of
different
toxicological
endpoints
via
the
dermal
and
oral
routes
of
exposure
for
children.
The
developmental
effects
used
to
assess
aggregate
risks
for
adult
females
are
not
appropriate
for
children.

5.3.2
Chronic
(
non­
cancer)
DWLOC
Calculations
As
noted
previously,
a
DWLOC
is
the
concentration
of
a
pesticide
in
drinking
water
that
would
result
in
risk
estimates
below
AD's
level
of
concern,
when
considering
total
aggregate
exposure
to
that
pesticide
from
food,
drinking
water,
and
residential
uses.
AD
uses
the
DWLOCs
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
associated
with
pesticide
exposure
through
drinking
water.
In
the
absence
of
monitoring
data
for
a
pesticide,
the
DWLOC
is
used
as
a
point
of
comparison
against
the
conservative
PECs
provided
by
computer
modeling.

AD
back­
calculates
the
chronic
DWLOCs
by
a
two­
step
process:
exposure
[
food+
(
if
applicable)
residential
exposure]
is
subtracted
from
the
chronic
PAD
to
obtain
the
maximum
exposure
allowed
in
drinking
water;
DWLOCs
are
then
calculated
using
that
value
and
default
body
weight
and
drinking
water
consumption
values.
In
assessing
human
health
risk,
the
chronic
DWLOCs
are
compared
to
the
PECs.
When
PECs
are
greater
than
DWLOCs
AD
considers
the
aggregate
risk
estimates
[
from
food
+
water
+
(
if
applicable)
residential
exposures]
to
exceed
the
Agency's
level
of
concern
(
HED
SOP
99.5
"
Standard
Operating
Procedures
for
Incorporating
Estimates
of
Drinking
Water
Exposure
into
Aggregate
Risk
Assessment,
August
1,
1999).

Table
10
presents
the
total
chronic
dietary
and
residential
exposure
estimates
for
zinc
pyrithione,
and
the
chronic
DWLOCs.
For
each
population
subgroup
listed,
the
chronic
PAD
and
35
the
chronic
dietary
(
food)
exposure
(
from
Table
4)
for
that
subgroup
were
used
to
calculate
the
chronic
DWLOC,
using
the
formulas
in
the
footnotes
of
Table
10.

Using
a
conservative
screening­
level
model,
the
range
of
PECs
for
zinc
pyrithione
in
a
marina
is
0.0144
to
0.101
ppb,
which
in
the
absence
of
additional
data
was
also
used
to
assess
chronic
exposures.
As
shown
on
Table
10,
the
chronic
DWLOCs
are
greater
than
the
PEC
for
adults
and
children,
indicating
that
aggregate
food,
residential
and
drinking
water
exposure
do
not
exceed
the
Agency's
level
of
concern.
The
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.

Table
10
DWLOCs
for
Chronic
Aggregate
Exposure
Population
Subgroup
Chronic
Scenario
cPAD
mg/
kg/
day
Chronic
Food
Exp
mg/
kg/
day
Chronic
Residential
Exposure
mg/
kg/
day5
Max
Chronic
Water
Exp
mg/
kg/
day1
Surface
Water
PEC
(
ppb)
2
Chronic
DWLOC
(

g/
L)
3
Potential
Risk
Concern4
Adults
(
Females
13­
50
years)
0.0016
0.000033
0.0014
0.00156
0.0144­
0.101
5
No
Infants/
Children
0.000067
NA
0.00153
15
No
NA=
Not
applicable.
For
children,
it
is
not
appropriate
to
aggregate
potential
chronic
dermal
exposures
from
a
shoe
liner
exposure
with
oral
exposures
because
of
different
toxicological
endpoints
via
the
dermal
and
oral
routes
of
exposure
for
children.
The
developmental
effects
used
to
assess
aggregate
risks
for
adult
females
are
not
appropriate
for
children.
1
Maximum
chronic
water
exposure
(
mg/
kg/
day)
=
[(
chronic
PAD
(
mg/
kg/
day)
­
(
chronic
food
exposure+
chronic
residential
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
60
kg
and
10
kg
for
adult
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?
5
Chronic
residential
exposure
consists
of
shampoo
exposure
(
0.001
mg/
kg/
day
based
on
absorbed
dermal
dose
estimate)
and
dermal
exposure
to
a
plastic
shoe
liner
(
4.06E­
4
mg/
kg/
day
absorbed
dose
estimate).
Dermal
exposures
are
aggregated
with
oral
exposure
for
adult
females
to
be
protective
of
potential
developmental
effects.

6.0
CUMULATIVE
EXPOSURE
AND
RISK
Another
standard
of
section
408
of
the
FFDCA
which
must
be
considered
in
making
an
unreasonable
adverse
effects
determination
is
that
the
Agency
consider
"
available
information"
36
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

Zinc
and
sodium
pyrithione
are
two
pesticide
active
ingredients
that
might
be
considered
together
in
a
common
mechanism
of
toxicity
assessment.
It
is
apparent
that
there
is
structural
similarity
between
these
two
chemicals
(
Step
1).
However,
the
zinc
pyrithione
pesticide
contains
two
pyrithione
moieties
whereas
the
sodium
pyrithione
pesticide
contains
only
one
pyrithione
moiety.
It
is
apparent
also
that
both
cause
neurotoxic
effects
at
similar
dose
levels
(
Step
2).
It
is
not
known
with
certainty,
however,
that
both
cause
this
effect
by
a
common
toxic
mechanism
(
Step
3).
In
addition,
the
hazard
data
suggest
pharmacokinetic
differences
in
the
behavior
of
the
two
pesticides.
There
are
also
differences
with
respect
to
use
sites.
Sodium
pyrithione
is
primarily
used
in
metalworking
and
cutting
fluids.
Zinc
pyrithione
is
not
registered
for
this
use.
The
sodium
omadine
®
(
sodium
pyrithione)
Reregistration
Eligibility
Document
(
RED)
also
states
that
"
the
amount
of
sodium
omadine
®
in
products
that
may
enter
the
home
or
occupational
setting
such
as
laundry
rinse
additives,
detergents,
carpet
cleaners,
emulsions
and
jet
printer
inks
would
be
very
low
due
to
dilution."
According
to
the
cumulative
risk
guidance,
"
a
particular
pathway
for
a
specific
chemical
...
should
be
removed
if
it
is
likely
to
contribute
only
a
very
small
percentage
of
the
total
exposure..."
Therefore,
it
is
unlikely
that
exposures
to
sodium
omadine
®
(
sodium
pyrithione)
will
occur
concomitant
with
any
exposures
to
zinc
pyrithione,
and,
for
those
that
may
occur
together,
the
contribution
of
sodium
pyrithione
to
the
total
exposure
would
be
very
low
and
would
not
be
included
in
a
cumulative
risk
assessment
at
this
time.

For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
zinc
pyrithione
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

7.0
OCCUPATIONAL
EXPOSURE
AND
RISK
AD
has
assessed
the
exposures
and
risks
to
occupational
workers
that
handle
zinc
pyrithione
(
memorandum
from
D.
Aviado/
D.
Smegal,
September
2004).
This
section
will
summarize
the
results
of
the
occupational
exposure
assessment.

Occupational
Handlers.
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.
An
exposure/
risk
assessment
for
occupational
antifoulant
boat
paint
use
is
not
included
in
this
document.
The
occupational
antifoulant
paint
use,
which
is
a
conditional,
time­
limited
registration,
will
be
assessed
in
the
future,
pending
the
submission
and
review
of
a
study
that
will
assess
exposure
of
workers
performing
painting
of
commercial
vessels
with
antifoulant
paints
containing
zinc
37
pyrithione.
This
study
is
expected
to
be
completed
in
2006.
The
occupational
exposure
scenarios,
and
estimated
risks
are
presented
on
Table
11.

Based
on
the
EPA­
registered
use
patterns,
appropriate
primary
and
secondary
handler
exposure
scenarios
were
identified
for
zinc
pyrithione.
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.

Primary
Occupational
Handlers.
The
exposure
and
risk
assessment
for
primary
occupational
handlers
was
conducted
using
product
label
maximum
application
rates,
related
use
information
from
Arch
Chemicals,
Inc.,
Agency
standard
values
for
industrial
practices,
and
CMA
unit
exposure
data.
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)
not
exceeding
the
Agency's
level
of
concern
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
liquids
for
all
the
scenarios
assessed.
Also,
the
dermal
and
inhalation
MOEs
for
the
laundered
fabrics
scenarios
were
not
of
concern.
However,
MOEs
from
exposures
exceed
the
Agency's
level
of
concern
(
i.
e.,
MOEs
<
100)
for
short­
term,
intermediate­
term,
and
long­
term
exposure
scenarios
during:

°
mixing/
loading/
applying
powders
and
liquids
for
general
preservative
use
patterns
using
open
pour
methods
(
inhalation
MOE=
53
for
liquid
formulations;
inhalation
MOE=
15
for
powder
formulation,
dermal
MOE=
42
for
powder
formulation);
and
°
mixing/
loading/
applying
powders
and
liquids
for
paint
preservation
using
open
pour
methods
(
inhalation
MOE=
53
for
liquid
formulations;
inhalation
MOE=
15
for
powder
formulation,
dermal
MOE=
42
for
powder
formulation).

The
Agency
may
consider
requiring
risk
mitigation
steps,
such
as
closed
delivery
systems
or
use
of
a
respirator
during
open
pouring.

Secondary
Occupational
Handlers.
Secondary
occupational
handler
exposures
could
occur
through
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
using
PHED
Version
1.1
data.

Using
product
label
maximum
application
rates,
related
use
information,
Agency
standard
38
values,
and
PHED
unit
exposure
data,
the
secondary
handler
potential
short­
term,
intermediateterm
and
long­
term
MOEs
exceed
the
Agency's
level
of
concern
(
MOEs
<
100)
for:

°
handling
zinc
pyrithione­
containing
paint
products
using
an
airless
sprayer
application
method
(
inhalation
MOEs=
4.4
without
PPE
and
44
with
the
use
of
a
respirator
as
PPE,
and
dermal
MOE=
11
without
PPE
and
MOE=
29
with
the
use
of
gloves
as
PPE),
and
°
handling
zinc
pyrithione­
containing
paint
products
using
a
paintbrush
(
Dermal
MOE=
22
without
gloves,
but
risks
are
not
of
concern
with
gloves).

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
as
PPE
recommended
by
paint
manufacturers
for
spray
equipment
applications.
Although
the
dermal
MOE
for
a
paintbrush
scenario
is
of
concern
(
MOE=
22)
without
gloves,
the
MOE
is
not
of
concern
(
MOE=
167)
when
gloves
are
worn
as
protective
equipment.
It
is
assumed
that
in
real­
use
situations
the
occupational
handlers
will
have
adequate
dermal
protection
by
wearing
gloves
as
may
be
recommended
by
paint
manufacturers.
Dermal
and
inhalation
MOEs
obtained
for
the
painting
scenario
involving
use
of
an
aerosol
spray
can
application
method
is
not
of
risk
concern.

Postapplication
Exposure
and
Risk.
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.
Thus,
postapplication
occupational
exposures
were
not
quantitatively
evaluated
in
this
report.

Table
11.
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
147
53
(
1b)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
metering
equipment
(
pump
liquid)
5
lb
ai/
1,000
lb
10,000
lb/
day
3,125
452
(
1c)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
open
pour
methods
5
lb
ai/
1,000
lb
10,000
lb/
day
42
15
Table
11.
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
39
(
1d)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
metering
equipment
(
automatic­
dispensing
techniques)
5
lb
ai/
1,000
lb
10,000
lb/
day
3,125
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
147
53
(
2b)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
metering
equipment
(
pump
liquid)
3,125
452
(
2c)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
open
pour
methods
42
15
(
2d)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
metering
equipment
(
automatic­
dispensing
techniques)
3,125
452
Primary
Occupational
Handler:
Fabrics/
Textiles:
Laundering
Treatment
for
Material
Preservation
(
3a)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
open
pour
methods
0.54
lb
ai/
1,000
lb
10,000
lb
1,370
487
(
3b)
Mixing/
loading/
applying
liquid
pesticide
concentrates
using
metering
equipment
(
pump
liquid)
29,412
4,180
(
3c)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
open
pour
methods
397
142
(
3d)
Mixing/
loading/
applying
powder
pesticide
concentrates
using
metering
equipment
(
automatic­
dispensing
techniques)
29,412
4,180
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
22
130
167
(
PPE)
(
f)
not
necessary
(
4b)
Handling
zinc
pyrithionecontaining
paint
end
products
using
an
airless
sprayer
application
method
5
lb
ai/
100
gal
50
gal/
day
11
4.4
29
(
PPE)
(
f)
44
(
PPE)(
f)
Table
11.
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
40
(
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)
376
500
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
NOAEL
is
0.5
mg/
kg/
day
from
the
rabbit
developmental
study.
A
3%
dermal
absorption
factor
was
used.
(
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.
Use
of
gloves
as
PPE
assumes
90%
protection
factor
on
hands.

8.0
INCIDENTS
There
are
no
reported
epidemiological
data
or
incident
information
for
zinc
pyrithione.

9.0
ENVIRONMENTAL
RISK
A
detailed
ecological
hazard
and
environmental
risk
assessment
for
zinc
pyrithione
is
presented
in
the
attached
memorandum
(
memo
from
K.
Montague
2004),
while
the
detailed
information
on
environmental
fate
is
presented
in
the
attached
memo
from
N.
Shamim
(
2004).
A
brief
summary
is
presented
below.

Environmental
Fate.
Zinc­
pyrithione
is
a
complex
(
coordination)
compound
formed
through
a
chemical
reaction
between
the
inorganic
zinc
ion
and
organic
moiety
pyrithione.

A.
Abiotic:

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
hydrolytic
half­
lives
were
99,
120
and
123
days
at
pHs
5,
7
and
9,
respectively.
In
simulated
sea
water,
the
extrapolated
half
life
was
96
41
days.
Photolytic
measurements
showed
that
zinc
pyrithione
rapidly
degrades
with
a
half
life
of
13
minutes
in
buffered
medium
and
in
about
17
minutes
in
simulated
sea
water.

B.
Biotic:

In
a
study
on
aerobic
aquatic
system,
zinc
pyrithione
degradation
follows
a
biphasic
process
and
in
the
first
phase
it
degrades
rapidly
with
a
half
life
of
0.065
hours
in
salt
water
and
in
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.
It
may
not
pose
a
concern
for
surface
water
runoff

A
second
aerobic
aquatic
degradation
study
was
conducted
on
a
salt
water
harbor
used
as
a
boat
maintenance
site.
Degradation
data
were
obtained
on
zinc
and
copper
pyrithiones.
In
water
samples,
and
in
the
presence
of
pyrithione
thiosulfate
(
OTS,
which
may
be
formed
as
a
degradate
or
may
be
present
in
the
sample),
the
half
life
was
0.60
hours.
Degradation
half
life
in
the
sediment
samples,
in
the
presence
of
OTS,
was
0.89
days,
(
OTS
may
be
initially
present
or
may
be
formed
due
to
degradation
process).
Kinetic
pathway
in
the
sediment
samples
was
non­
linear.
In
the
absence
of
OTS,
and
through
non­
linear
pathway,
the
degradation
half
life
decreased
to
0.03
days.
The
sediment
in
this
study
was
characterized
as
sand
(%
sand
=
90,
silt:
4%
and
clay:
6%)

In
anaerobic
aquatic
samples
from
fresh
and
salt
water,
zinc
pyrithione
degraded
through
biphasic
process.
Anaerobically
fresh
water
and
salt
water
samples
of
zinc
pyrithione
degraded
rapidly
in
the
first
phase
with
a
half
life
of
about
2
hours.
In
the
second
phase,
the
degradation
half
life
in
fresh
and
salt
water
samples
increased
to
25.5
hours.
Fresh
water
and
salt
sediment
samples,
zinc
pyrithione
degradation
half
was
measured
at
13.1
hours.

In
a
second
study,
water
and
sediment
samples
were
collected
from
a
salt
marina
(
Little
Harbor,
MarbleHead,
MA).
A
two
compartment
model
was
used
to
analyze
the
kinetic
data:
zinc
pyrithione
degraded
in
0.50
hours
in
water
sample
and
in
18.9
hours
in
the
sediment
sample.
The
sediment
of
this
marina
was
characterized
as
sand
(
%
sand
=
86,
silt:
6%,
and
clay:
8%).
pH
of
the
sediment
was
basic
(
7.9)
and
%
organic
C
=
2.3.

A
soil
column
leaching
study
conducted
on
four
soil
samples:
sand,
sandy
loam,
loam
and
clay
(
unaged)
and
on
sandy
loam
(
aged)
indicated
that
zinc
pyrithione
is
immobile
in
these
systems.

An
absorption/
desorption
study
conducted
on
Marblehead
salt
water
soil,
Marblehead
salt
water
sediment,
Portland
freshwater
soil
and
Portland
freshwater
sediment
(
all
from
MA),
showed
that
zinc
pyrithione
binds
moderately
strongly
with
Marble
saltwater
soil
and
sediment
(
K
d=
50
and
99
respectively)
and
less
strongly
with
Portland
freshwater
soil
and
sediment
(
K
d
=
11
and
48).
Marblehead
salt
water
soil
and
sediment
were
characterized
as
sandy
loam
and
Portland
freshwater
soil
and
sediment
as
loamy
or
silt
loam.
42
For
use
of
zinc
pyrithione
as
an
antifoulant
paint
on
small
boat
and
ship
bottoms
a
special
study
called
Aqueous
Availability
study
which
measures
the
rate
of
leaching
when
boats
and
ships
painted
with
the
antifoulant
paint
navigate
in
fresh
or
salt
water
bodies
(
marinas,
or
lakes
or
sea)
,
a
number
of
aqueous
availability
studies
were
conducted
on
a
number
formulations
containing
zinc
pyrithione
and
in
some
cases
zinc
pyrithione
and
another
biocide.
The
percent
of
zinc
pyrithione
in
the
formulations
varied
from
2.0
to
4.7
and
the
average
leach
rate/
day
ranged
from
1.2
µ
g/
cm2/
day
to
8.4
µ
g/
cm2/
day.
These
were
non­
guideline
studies
and
aqueous
availability
studies
were
carried
by
using
the
EPA
approved
ASTM
Method
D
5108­
90.

The
Octanol/
Water
Partition
Coefficient
(
K
OW)
of
zinc
pyrithione
is
reported
to
be
less
than
10
(
Log
Kow
is
0.97)
which
makes
it
less
likely
to
bioaccummulate
in
aquatic
organisms,
although
because
of
moderately
high
K
d
s
with
salt
water
sediments
it
may
and
partition
in
water
and
become
available
to
benthic
organisms.

Coordination
or
complex
substances
like
zinc
pyrithione
have
a
tendency
to
transmetallate
with
other
metals
present
in
aquatic
media
(
copper,
mercury,
cadmium
and
other
metal
ions).
Copper
pyrithione
is
shown
to
be
more
stable
than
zinc
pyrithione.
However,
it
also
degrades
with
comparable
rates
as
zinc
pyrithione
in
the
aerobic
and
environmental
media
of
water
and
sediments.

The
registrant
recently
submitted
as
outdoor
microcosm
study
(
MRID
45876501),
which
is
not
required
by
environmental
fate
requirements.
This
study
was
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.

Environmental
Modeling/
Exposure.
The
limited
environmental
exposure
resulting
from
indoor
uses
of
zinc
pyrithione
is
not
anticipated
to
cause
adverse
effects
to
terrestrial
or
aquatic
organisms.

Ecological
Hazard
and
Risk.
The
ecological
effects
database
for
zinc
pyrithione
is
adequate
to
support
the
indoor
uses
considered
in
this
risk
assessment.
The
ecological
risks
associated
with
the
outdoor
antifoulant
boat
use,
which
is
conditionally
registered
until
June
2005,
are
not
included
in
this
report,
but
will
be
evaluated
upon
review
of
recently
submitted
ecotoxicity
studies.
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
moderately
toxic
to
mammals
via
oral
ingestion
(
Toxicity
Category
II).
Zinc
pyrithione
is
very
highly
toxic
on
an
acute
basis
to
freshwater
and
marine
fish
and
invertebrates,
as
well
as
to
aquatic
plant
species.
Zinc
pyrithione
caused
impacts
on
growth
and
reproduction
to
several
species
of
aquatic
organisms
in
laboratory
studies,
at
levels
slightly
below
the
LC50.
These
types
of
effects
suggest
that
zinc
pyrithione
may
43
possibly
have
endocrine
disruption
potential.
The
acute
toxicity
data
for
zinc
pyrithione
are
summarized
on
Table
12.
Plant
toxicity
data
are
presented
on
Table
13,
while
chronic
ecotoxicity
data
are
presented
on
Table
14.

Table
12
Acute
Toxicity
of
Zinc
Pyrithione
Species
LD50/
LC50
(
95
%
c.
i)
NOAEL/
NOAEC
Toxicity
category
Birds
Northern
bobwhite
(
Colinus
virginianus)
60
mg/
kg
(
44
­
81)
<
31.2
ppm
moderately
toxic
Northern
bobwhite
(
Colinus
virginianus)
1063
mg/
kg
(
789
­
1412)
<
253
ppm
slightly
toxic
Mallard
(
Anas
platyrhynchos)
>
5000
mg/
kg
(
NA)
<
275
ppm
practically
non­
toxic
Mammals
Laboratory
rat
(
Rattus
norvegicus)
267
mg/
kg
NA
moderately
toxic
Freshwater
Fish
Rainbow
trout
(
Oncorhynchus
mykiss)
3.6
ppb
(
3.07
­
4.33)
1.6
ppb
very
highly
toxic
Fathead
minnow
(
Pimephales
promelas)
2.68
ppb
(
2.10
­
3.27)
1.1
ppb
very
highly
toxic
Freshwater
Invertebrate
Waterflea
(
Daphnia
magna)
8.25
ppb
(
5.24
­
25.82)
<
1.1
ppb
very
highly
toxic
Freshwater
amphipod
(
Hyalella
azteca)
136
ppb
NA
highly
toxic
Table
12
Acute
Toxicity
of
Zinc
Pyrithione
Species
LD50/
LC50
(
95
%
c.
i)
NOAEL/
NOAEC
Toxicity
category
44
Estuarine/
Marine
Fish
Sheepshead
minnow
(
Cyprinodon
variegatus)
400
ppb
(
200­
590)
200
ppb
highly
toxic
Estuarine/
Marine
Invertebrates
Eastern
oyster
(
Crassostrea
virginica)
shell
deposition
22.0
ppb
(
18.9
­
27.3)
7.1
ppb
very
highly
toxic
Mysid
(
Mysidopsis
bahia)
4.7
ppb
(
4.04­
5.53)
1.6
ppb
very
highly
toxic
NA
=
not
available
NOAEC=
No­
observable
adverse
effect
concentration
Table
13
Plant
Toxicity
Data
for
Zinc
Pyrithione
Species
LD50/
LC50
(
ppb)
(
95
%
c.
i)
NOEC
(
ppb)
MRID
Alga
and
Aquatic
Plants
Freshwater
green
alga
(
Selenastrum
capricornutum)
28.0
(
24.3­
33.0)
7.8
43864609
Blue­
green
alga
(
Anabaena
flos­
aquae)
7.1
3.8
45564901
Freshwater
diatom
(
Navicula
pelliculosa)
2.6
2.4
45565001
Aquatic
vascular
plant,
duckweed
(
Lemna
gibba)
8.87
4.0
45204104
NOEC=
No­
observable
effect
concentration
45
Table
14
Chronic
Ecotoxicity
Data
for
Zinc
Pyrithione
Species
NOAEL/
LOAEC
(
ppb)
Toxicity
category
or
Endpoint
Affected
Freshwater
Fish
Early
Life­
Stage
Toxicity
Data
Fathead
minnow
(
Pimephales
promelas)
1.22/
2.82
Survival,
sublethal
effects
(
bent
spinal
columns)
and
length
Freshwater
Invertebrate
Life­
Cycle
Toxicity
Data
Waterflea
(
Daphnia
magna)
2.7
/
5.8
Reproduction
length
Estuarine/
Marine
Invertebrates
Mysid
(
Mysidopsis
bahia)
growth:
2.28;
repro:
4.2
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally­
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
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
effects
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.

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
various
degradates
in
aquatic
systems,
aquatic
organism
acute
toxicity
tests
with
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;
these
degradates
are
not
expected
to
cause
adverse
acute
or
chronic
effects
to
terrestrial
or
aquatic
organisms.
Toxicity
data
for
the
degradates
of
zinc
pyrithione
are
presented
on
Table
15.
46
Table
15
Ecotoxicity
Data
for
zinc
pyrithione
degradates
Species
LC50
(
ppb
ai)
(
95%
c.
i.)
NOAEC
(
ppb
ai)
Toxicity
Category
Pyridine­
2­
sulfonic
acid
Rainbow
trout
(
Oncorhynchus
mykiss)
57100
(
48300
­
69800)
46900
slightly
toxic
Fathead
minnow
(
Pimephales
promelas)
68500
(
55200
­
85000)
55200
slightly
toxic
Waterflea
(
Daphnia
magna)
>
122000
122000
practically
non
toxic
Sheepshead
minnow
(
Cyprinodon
variegatus)
>
127000
127000
practically
nontoxic
Eastern
oyster
(
Crassostrea
virginica)
shell
deposition
85600
(
73300
­
102500)
51100
slightly
toxic
Mysid
(
Mysidopsis
bahia)
71000
(
62800­
81100)
51900
slightly
toxic
Freshwater
green
alga
(
Selenastrum
capricornutum)
28900
(
23000
­
46200)
5460
slightly
toxic
Freshwater
Fish
Early
Life­
Stage:
Fathead
minnow
(
Pimephales
promelas)
NA
10
NA
Pyrithione
sulfonic
acid
Rainbow
trout
(
Oncorhynchus
mykiss)
92300
(
73600
­
124000)
73600
slightly
toxic
Fathead
minnow
(
Pimephales
promelas)
58800
(
48700
­
71000)
48700
slightly
toxic
Waterflea
(
Daphnia
magna)
>
127000
32800
practically
nontoxic
Sheepshead
minnow
(
Cyprinodon
variegatus)
>
137000
137000
practically
nontoxic
Eastern
oyster
(
Crassostrea
virginica)
shell
deposition
96200
(
89313
­
104560)
21900
slightly
toxic
Mysid
(
Mysidopsis
bahia)
70300
(
61600­
81600)
19400
slightly
toxic
Table
15
Ecotoxicity
Data
for
zinc
pyrithione
degradates
Species
LC50
(
ppb
ai)
(
95%
c.
i.)
NOAEC
(
ppb
ai)
Toxicity
Category
47
Freshwater
green
alga
(
Selenastrum
capricornutum)
28200
(
26000
­
30800)
11800
slightly
toxic
NOAEC=
No­
observable
adverse
effect
concentration
NA=
Not
applicable
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
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
described
in
Section
IV
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.

10.0
DEFICIENCIES/
DATA
NEEDS
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
required
as
confirmatory
data
for
this
chemical
in
order
to
characterize
this
type
of
toxicity.
The
developmental
neurotoxicity
study
is
in
"
reserve"
pending
the
results
of
the
48
acute
and
subchronic
neurotoxicity
studies.

In
addition,
five
ecotoxicity
studies
were
recently
submitted
to
the
Agency.
These
studies
include:
two
terrestrial
plant
toxicity
studies
(
OPPTS
guidelines
850.4225
and
850.4250),
a
study
on
the
influence
on
growth
and
growth
rate
of
the
marine
diatom,
Skeletonema
coatatum
(
Guideline
123­
2),
and
two
sediment
toxicity
tests
(
for
freshwater
amphipod,
Hyalella
azteca,
Guideline
OPPTS
850.1735,
and
marine
amphipod,
Leptocheirus
plumulosu,
Guideline
OPPTS
850.1735).

A
worker
study
is
currently
under
development
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
during
outdoor
painting
of
ship
hulls
with
intersmooth
360
or
460
Ecoloflex
SPC
Antifouling
(
Guidelines
875.1100
and
875.1300).

Confirmatory
worker
exposure
data
are
necessary,
due
to
the
significant
limitations
of
the
existing
exposure
data
used
in
this
assessment.
The
Agency
is
requesting
six
worker
exposure
studies
that
evaluate
both
dermal
(
Guideline
875.1100)
and
inhalation
(
Guideline
875.1300)
exposure
for
the
following
scenarios:
(
1)
open
pour
of
liquids;
(
2)
metering
pump
for
liquids
(
closed
loading
system);
(
3)
open
pour
of
powder;
(
4)
automatic­
dispensing
systems
for
powders;
(
5)
painting
with
a
brush/
roller/
airless
sprayer;
and
(
6)
aerosol
can
spray.

11.0
REFERENCES
Adams,
Wedig,
et
al.
1976.
Urinary
Excretion
and
Metabolism
of
Salts
of
2­
Pyridinethiol­
1­
oxide
following
intravenous
administration
to
female
Yorkshire
pigs.
Toxicology
and
Applied
Pharmacology.
36:
523­
531.

Garrod
ANI,
Guiver
R,
Rimmer
DA.
2000.
Potential
Exposure
of
Amateurs
(
Consumers)
through
Painting
Wood
Preservative
and
Antifoulant
Preparations.
Ann.
Occup.
Hyg.,
Vol.
44,
No.
6,
pp.
421­
426.

Grant
1993
W.
M.
Toxicology
of
the
Eye.
3rd
ed.
Springfield,
IL.
Charles
C.
Thomas,
Pub
Klaassen,
C
(
1976):
Absorption,
Distribution,
and
Excretion
of
Zinc
Pyridinethione
in
Rabbits.
Toxicol.
Appl.
Pharmacol.
35:
581­
587.

Larson,
P.
S.
1958.
Toxicologia
Observation
on
the
Effect
of
Adding
Zn
Pyridinethiene
to
the
Diet
of
Rats
for
a
period
of
two
years.
(
August
18,
1958).
P.
S.
Larson,
Professor
of
Pharmacology,
Medical
College
of
VA.
TOX
Record
No.
003933.

Ross,
J.
F.
and
Lawhorn,
G.
T.
(
1990):
ZPT­
related
Distal
Axonopathy:
behavioral
and
electrophysiologic
correlates
in
rats.
Neurotoxicol.
Teratol
12(
2):
153­
159,
1990
49
Snyder,
D.
R.,
deJesus,
C.
P.
V.,
Towfighi,
J.,
Jacoby,
R.
O.,
Wedig,
J.
H.
(
1979):
Neurological,
Microscopic,
and
Enzyme­
Histochemical
Assessment
of
Zinc
Pyrithione
Toxicity.
Food
Cosmet.
Toxicol.
17(
6),
651­
660,
1979.

Wedig,
J.
H.,
et
al.
(
1978):
Disposition
of
Zinc
Pyrithione
in
the
Rat.
Fd.
Cosmet.
Toxicol.
16:
553­
561.