Document ID: EPA-HQ-OPP-2004-0147-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-06-18T04:00Z

1
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
April
28,
2004
SUBJECT:
Zinc
Pyrithione
(
Zinc
Omadine):
AD
Response
to
Registrants
"
Error
Correction"
Comments
Chemical
No.
088002.
Case
No.
2480.
DP
Barcode:
D301374
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
Team
34,
Reregistration
Antimicrobials
Division
(
7510C)

General
All
error
comments
were
corrected
and
many
of
the
other
registrant
comments
were
also
addressed.
For
example,
the
Agency
has
refined
its
environmental
modeling
using
the
Marine
Antifoulant
Model­
Predicted
Environmental
Concentration
(
MAM­
PEC)
model.
The
revised
2
PECs
range
from
0.0144
to
0.101
ppb,
compared
to
the
previous
value
of
21.66
ppb.
In
addition,
the
ecological
hazard
and
environmental
risk
assessment
was
revised
to
remove
all
discussion
of
the
risks
from
the
antifouling
use,
pending
the
submission
of
five
ecological
effects
studies,
which
are
required
to
support
the
antifouling
use.
The
ecological
risk
assessment
for
the
antifouling
use
will
be
revised
upon
submission
of
these
ecotoxicity
studies.

Registrant
Comment:
A.
Executive
Summary,
page
1,
2nd
paragraph
reads
" 
for
use
in
dandruff
shampoos."

Should
read
" 
for
use
in
Anti­
dandruff
shampoos."

Further,
the
following
statement
would
provide
a
complete
description
of
its
use
in
this
FDA
approved
application:
"
It
is
considered
safe
ands
effective
(
considered
both
GRAS
and
GRAE
and
Category
I
by
USFDA)
for
the
treatment
of
dandruff
and
seborrheic
dermatitis
with
a
history
of
over
40
years
of
human
use."

EPA
Response:
The
term
dandruff
shampoo
was
changed
to
"
anti­
dandruff
shampoo"
throughout
the
document.
The
suggested
language
was
adopted.

Registrant
Comment:

B.
Hazard,
page
1,
2nd
paragraph,
1st
sentence
states:
"
The
oral
LD
50
range
from
460­
630
mg/
kg"

Should
read:
The
combined
oral
LD50
in
rats
is
269
mg/
kg
ranging
from
221
 
302
mg/
kg.

EPA
Response:
The
oral
rat
LD50
was
changed
to
267
mg/
kg,
based
on
an
acceptable
study
conducted
with
95%
ai
technical
zinc
omadine
(
Tox
record
003933).

Registrant
Comment:

C.
Hazard,
page
1,
2nd
paragraph,
2nd
sentence:
"
Acute
Toxicity
by
the
inhalation
route
is
also
relatively
low
(
0.61
mg/
L;
Toxicity
Category
III)."

Should
read:
" 
relatively
low
(>
0.61
mg/
L; "
needs
insertion
of
a
"
greater
than"
symbol.

Comment:
Acute
Inhalation
LC50
for
zinc
pyrithione
a.
i.
100%
powder
is
>
0.61
mg/
L
(
only
1
out
of
10
deaths
at
0.24
mg/
L
and
3
out
of
10
deaths
at
0.61
mg/
L,
but
in
the
interest
in
saving
animals
no
further
doses
were
tested
and
the
Toxicity
Category
III
classification
for
inhalation
was
accepted)
and
recent
testing
of
the
48%
zinc
OMADINE

aqueous
dispersion
the
acute
inhalation
LC50
was
5.08
mg/
L
for
the
dispersion
following
a
4­
hr.
nose­
only
exposure.
3
EPA
Response:
The
suggested
change
was
made.

Registrant
Comment:

D.
Hazard,
page
1,
last
paragraph,
last
sentence,
"
Developmental
toxicity
using
the
oral
route
of
administration
show
zinc
OMADINE

to
produce
significant
developmental
effects
which
are
greater
in
severity
(
of
developmental
toxicity)
at
doses
of
1.5
and
3.0
mg/
kg/
day
than
toxicity
observed
in
maternal
animals
at
these
same
dose
levels".

Should
read:
"
Developmental
toxicity
studies
using
the
oral
route,
produced
developmental
toxicity
at
doses
that
produced
significant
maternal
toxicity
during
sensitive
times
of
development."

Comment:
Based
on
the
Data
Evaluation
Report
(
DER);
EPA
Reviewer
John
E.
Whalen
in
1996,
"
A
decrease
in
body
weight
gain
(
p 
0.01)
during
the
dosing
period
for
the
mid
(
1.5
mg/
kg/
day)
and
high­
dosed
(
3.0
mg/
kg/
day)
(
41%
and
99%,
respectively)
cannot
be
considered
to
be
biologically
significant
since
the
absolute
body
weight
changes
were
only
~
4%
and
~
6%..."

The
reference
of
4
and
6%
relates
to
the
changes
in
absolute
body
weight
over
the
entire
gestation
period
days
0­
29
and
the
41%
and
99%
decrease
in
body
weight
gains
were
observed
over
gestation
days
0­
19,
dosing
ceased
on
gestation
day
19
and
yes
there
was
a
rebound
in
body
weight
after
cessation
of
treatment.
In
addition,
the
DER
stated
that
there
was
no
corresponding
decrease
in
food
consumption.
However,
in
the
same
DER
report
of
the
zinc
OMADINE

Developmental
Toxicity
Study
in
the
Rabbit
Table
3.0
Food
Consumption
shows
a
statistically
significant
decrease
in
food
consumption
for
gestation
days
6­
19.
Body
weight
gains
from
gestation
days
6­
19
achieved
statistical
significance
of
p
 
0.01
that
corresponded
precisely
to
a
decrease
in
food
consumption
of
16%
(
mid­
dose,
1.5
mg/
kg/
day)
and
23%
(
high­
dose,
3.0
mg/
kg/
day).
Therefore
it
should
be
concluded
that
severe
maternal
toxicity
was
observed
in
the
mid
and
high­
dosed
animals
during
a
very
sensitive
time
for
development.
The
NOEL
for
maternal
and
developmental
effects
was
0.5
mg/
kg/
day
based
on
severe
maternal
toxicity
at
1.5
and
3.0
mg/
kg/
day.

EPA
Response:

The
following
language
was
added
to
replace
the
language
in
question.
"
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).
"

This
language
reflects
both
the
rat
and
rabbit
developmental
studies,
and
is
consistent
with
language
in
the
ADTC
2004
and
HIARC
1999
memos,
which
were
reviewed
by
between
10
and
4
12
senior
toxicologists.
Maternal
toxicity
was
minimal
in
the
rat
developmental
study,
as
salivation
was
noted
in
27%
of
the
animals
at
3
mg/
kg/
day.

Registrant
Comment:

E.
Hazard,
page
2,
1st
paragraph,
2nd
&
3rd
sentences,
"
Intravenous
administration
of
5mg/
kg
zinc
OMADINE

to
female
Yorkshire
pigs
produced
cholinergic
effects
lasting
for
30­
60
minutes
post­
dose
(
HED
document
003933).
Increased
salivation
was
reported
immediately
after
dosing
in
the
rat
developmental
toxicity
study
at
a
dose
of
3
mg/
kg/
day
(
MRID#
4287904)".

Should
read:
"
Intravenous
administration
of
5mg/
kg
zinc
OMADINE

to
female
Yorkshire
pigs
produced
symptoms
similar
to
cholinergic
effects
lasting
for
30­
60
minutes
post­
dose.
Increased
salivation
was
reported
immediately
after
dosing
in
the
rat
developmental
toxicity
study
at
a
dose
of
3
mg/
kg/
day
(
MRID#
4287904)
(
possibly
due
to
the
fact
that
zinc
pyrithione
causes
significant
irritation
to
mucosal
membranes
and
it
is
not
uncommon
to
observe
increased
salivation
following
oral
administration
from
such
compounds)."

Comment:
Another
explanation
for
the
observation
of
an
increase
in
salivation
could
be
the
fact
that
zinc
OMADINE

is
severely
irritating
to
mucosal
membranes
and
it
is
not
uncommon
to
observe
increased
salivation
following
oral
gavage
of
such
compounds.
Reference
to
hindlimb
weakness
in
the
same
paragraph
seems
suggestive
that
such
an
effect
possibly
is
indicative
of
cholinergic
effects.
We
would
like
to
reiterate
the
fact
that
hindlimb
weakness
has
only
been
observed
in
rats
and
rabbits
and
has
never
been
observed
in
dogs
or
primates
when
tested
at
much
higher
concentrations
for
up
to
one
year
of
exposure.

EPA
Response:
No
change
was
made.
The
existing
language
is
consistent
with
the
EPA
Data
Evaluation
Report
(
DER)
for
this
study.

Registrant
Comment:

F.
Toxicity
Endpoints,
page
2,
1st
sentence
reads
" 
to
assessment
potential
risks "

Should
read
" 
to
assess
potential
risks "

EPA
Response:
The
suggested
change
was
made.

Registrant
Comment:

G.
Water
Exposure
&
Risk,
page
4,
1st
sentence
"
AD
has
considered
the
registered
uses
of
zinc
OMADINE

and
the
available
data
on
persistence
and
mobility"
5
Should
read:
"
AD
has
considered
the
registered
uses
of
zinc
OMADINE

and
used
the
available
data
on
only
abiotic
hydrolysis
conducted
in
the
dark
with
sterile
water"

Comment:
Regarding
mobility
and
potential
impact
on
surface
and
ground
water
resources,
it
does
not
appear
that
the
Agency
has
considered
the
available
data
on
mobility
(
Abs/
Des,
Soil
Column
Leaching
MRID#'
s
44010402
&
45565201).
Zinc
OMADINE

is
classified
as
immobile
in
sediments
and
soils
and
is
not
likely
to
get
into
ground
water.
Since
recreational
boating
in
seawater
will
not
impact
drinking
water,
only
the
implication
of
surface
freshwater
should
be
considered
as
it
pertains
to
untreated
drinking
water.
Arch
disagrees
with
the
statements
made
in
the
Water
Exposure
and
risk
section
and
further
comments
follow.

EPA
Response:
The
language
was
modified
to
be
consistent
with
the
revised
Environmental
Fate
Chapter.

Registrant
Comment:

H.
Water
Exposure
and
Risk,
page
4,
3rd
sentence
" 
PEC
of
21.66
ppb
zinc
OMADINE

was
estimated
using
the
Luttik
Johnson
model".

Should
read
" .
PEC
of
21.66
ppb
zinc
OMADINE

was
estimated
by
using
the
Luttik
Johnson
model
that
used
a
leach
rate
input
of
12.5
µ
g/
cm2/
day
and
abiotic
hydrolysis
(
conducted
in
the
dark
with
sterile
water)
half
life
of
123
days.
Other
models
that
allow
use
of
relevant
environmental
parameters
provide
a
PEC
value
of
0.12
ppb
(
EXAMS).
Luttik­
Johnson
model
using
a
composite
degradation
rate
from
multiple
degradation
pathways
gives
a
PEC
value
of
0.16
ppb
"

Comment:
Arch
strongly
disagrees
with
agency's
approach
to
calculation
of
the
predicted
environmental
concentration
(
PEC)
of
21.66
ppb
using
the
Luttik
Johnson
model.
It
is
clear
from
the
PEC
calculation
that
the
agency
has
not
considered
all
available
data
on
degradation
and
persistence.
For
assessing
persistence,
only
hydrolysis
in
dark,
sterile
fresh
water
was
considered
by
the
agency.
Accepted
guideline
studies
on
photolysis
and
aerobic
and
anaerobic
metabolism
(
MRIDs
44011501,
44010401,
44850002)
show
that
zinc
pyrithione
has
a
short
half­
life
in
the
environment
and
these
studies
are
more
relevant
to
environmental
fate
than
abiotic
hydrolysis.
(
On
page
11
of
the
RED
document,
the
Agency
does
take
these
studies
into
account
and
states
that
zinc
OMADINE

has
a
"
fairly
short
half­
life,
ranging
from
hours
to
days").
Because
incorrect
parameters
were
used
in
the
modeling,
the
resulting
PEC
of
21.66
ppb
is
ten­
fold
higher
than
the
highest
measured
concentration
reported
for
a
persistent
co­
biocide
(
the
highest
measured
concentrations
are
1.7
 
2.1
µ
g/
L
for
Irgarol,
MRID#
46101101).
Since
zinc
pyrithone
is
short­
lived,
logic
dictates
that
its
measured
concentrations
will
be
even
lower.
Although
there
have
6
been
attempts
to
measure
zinc
OMADINE

in
the
environment,
it
has
not
been
detected
yet
(
detection
limit
=
0.02
µ
g/
L;
MRID#
46101101).

The
Luttik­
Johnson
model
used
is
inadequate
for
generating
environmentally
relevant
PECs.
Refinement
of
modeling
by
the
Agency
is
suggested
as
other
International
Government
Agencies
are
using
models
(
MAM­
PEC,
EXAMS,
REMA)
that
are
better
predictors
of
realistic
PECs.
Some
of
the
shortcomings
of
the
Luttik­
Johnson
model
are:

a)
No
hydrodynamic
water
exchange
component
b)
No
consideration
for
effects
of
temp,
salinity,
pH
c)
Only
one
degradation
pathway
is
input
The
key
parameters
that
impact
the
PEC
are
the
leach
rate
and
the
degradation
rate.
Arch
has
evaluated
all
the
widely
used
models
for
risk
assessment
for
antifoulant
biocides
and
submitted
a
comprehensive
document
for
agency
to
review
(
MRID
46101101).
That
document
has
not
been
reviewed
for
the
RED.
(
see
Calculation
of
Predicted
Environmental
Concentrations
of
Zinc
Pyrithione
in
Antifouling
Applications
(
MRID
46101101).
The
input
value
of
12.5
µ
g/
cm2/
day
for
the
leach
rate
in
the
Luttik­
Johnson
model
is
an
abnormal
value
based
on
one
paint
that
is
not
a
commercial
paint.
Subsequent
MRID
submissions
show
actual
data
on
commercial
paints
(
see
range
in
following
Table
1).
MAM­
PEC
which
is
a
widely
recognized
model
used
for
risk
assessment
of
antifoulant
paints
uses
2.5
µ
g/
cm2/
day
for
different
biocides
in
assessing
risk.
The
2.5
µ
g/
cm2/
day
is
based
on
mass
balance
and
coating
lifetime
calculations.
The
leach
rate
of
12.5
µ
g/
cm2/
day
would
mean
a
coating
lifetime
of
20%
of
that
guaranteed
by
the
paint
company
(
normally
5
yrs)
 
and
therefore
an
impossibly
high
leach
rate.
The
risks
are
directly
proportional
to
the
environmental
concentrations,
which
are
in
turn
directly
proportional
to
biocide
release
rates
and
inversely
proportional
to
biocide
degradation
and
environmental
transport
rates.

Also
the
PEC
derived
from
Luttik­
Johnson
model
should
not
be
used
for
comparison
to
drinking
water
level
of
comparison
(
DWLOC)
as
the
model
only
relates
to
a
marina
or
a
harbor.
Given
the
fast
degradation
through
multiple
pathways,
it
is
unlikely
that
the
PEC
of
21.66
ppb
could
be
a
valid
number
for
DWLOC.
It
is
not
realistic
to
assume
that
water
from
the
marina
can
be
used
as
potable
water
without
treatment.

Because
of
the
limitations
of
the
Luttik­
Johnson
model,
European
regulatory
bodies
have
used
more
appropriate
models
like
MAM­
PEC,
EXAMS
or
REMA
which
all
give
lower
PEC
values
for
zinc
OMADINE

in
a
marine
paint
application
(<
0.1
ppb)

With
a
realistic
PEC,
which
should
be
100­
1000
times
lower,
there
is
no
risk.
The
leach
rate
of
12.5
µ
g/
cm2/
day
is
an
impossibly
high
leach
rate
for
commercial
AF
paints
leading
to
an
improbable
PEC
of
21.66
ppb
and
it
is
simply
incorrect
to
call
this
a
"
conservative"
leach
rate
or
call
the
PEC
a
"
conservative"
PEC.
7
The
use
of
refined
PEC
values
was
discussed
in
July
2003
at
a
meeting
between
Arch
and
EPA
personnel.
At
that
meeting,
EPA's
Antimicrobial
Division
environmental
and
regulatory
reviewers
suggested
that
Arch
submit
a
discussion,
explanation
and
rationale
for
the
refined
PEC
values
and
a
justification
for
not
relying
on
the
ASTM
release
rate
and
for
not
using
the
present
PEC
values
in
the
assessment
of
zinc
pyrithione.
Arch
believes
that
this
report
(
MRID
46101101)
fully
satisfies
that
request
and
provides
a
definitive
basis
for
use
of
a
redefined
PEC
value.

Additionally,
in
an
outdoor
Microcosm
Study
(
2003,
MRID
45876501)
it
was
shown
that
ZPT
degraded
rapidly
with
a
half­
life
of
36
minutes.
This
is
similar
to
the
half­
life
seen
in
photolysis
study
(
half­
life
of
13
­
17
minutes
at
250C).
At
4hr.,
no
ZPT
was
detected
in
the
water
(
det.
limit
=
0.02
ppb).
In
the
sediment,
ZPT
reached
a
maximum
of
0.46%
at
day
1
and
was
not
detected
at
and
after
day
7.
The
amount
of
bound
residues
was
5.6
­
6.9%
at
the
end
of
the
study.
In
a
dark
microcosm
study,
ZPT
decreased
to
4%
of
the
starting
dose
at
day
1
and
was
not
detectable
by
day
7.
The
half­
life
in
this
dark
study
is
estimated
to
be
20
hr.
In
the
sediment,
ZPT
was
not
detectable
at
day
7.
The
only
significant
degradation
product
after
30
days
was
2­
pyridine
sulfonic
acid
accounting
for
69­
76%
of
the
total
radioactivity.
Amount
of
bound
residues
ranged
from
5­
7%
of
the
total
radioactivity
in
the
end
of
the
study.
This
outdoor
study
simulating
environmental
conditions
provides
multiple
environmental
degradation
pathways
that
show
that
zinc
OMADINE

rapidly
degrades
in
the
environment.

Whereas
the
Agency
assumed
a
release
rate
of
12.5
µ
g/
cm2/
day,
Arch
used
a
value
of
2.5
µ
g/
cm2/
day
which
is
in
the
range
of
leach
rates
obtained
from
commercially
registered
paint
leach
rate
studies.
The
Agency
release
rate
appears
to
be
biased
by
the
ASTM
release
rate
of
an
early,
experimental
paint
that
was
never
commercialized
and
is
not
representative
of
commercial
antifouling
paints
containing
zinc
pyrithione.

For
the
degradation
rate
of
zinc
pyrithione,
the
Agency
used
a
half­
life
of
123
days,
which
is
extrapolated
from
a
30
day
hydrolysis
study
carried
out
in
sterile,
synthetic
seawater
in
the
absence
of
light.
The
corresponding
rate
constant
was
entered
into
the
Luttik­
Johnson
emission
model
to
obtain
the
PEC.
In
comparison,
Arch
input
rate
data
from
several
environmental
fate
studies
 
hydrolysis,
photolysis,
aerobic
and
anaerobic
aquatic
metabolism,
die­
away,
adsorption/
desorption
 
into
chemical
fate
models
capable
of
integrating
multiple
degradation
processes
(
including
the
Luttik­
Johnson
model)
to
give
an
overall
degradation
rate
for
a
particular
environmental
scenario
(
see
Table
2).
Because
pyrithione
undergoes
biolysis,
photolysis
and
sediment­
catalyzed
degradations,
it
is
necessary
to
use
multi­
fate
exposure
models
such
as
EXAMS
and
MAM­
PEC.
EXAMS,
with
its
extensive
photolysis
algorithms,
was
found
to
be
the
most
suitable
modeling
program
for
zinc
pyrithione.
EXAMS
calculates
a
half­
life
of
<
12
hours
for
the
EPA
scenario.
Arch,
using
the
same
environmental
scenario
as
the
agency
uses,
but
with
more
current
data
on
release
rates
and
degradation
rates
as
input
in
different
exposure
models,
calculated
a
PEC
of
8
0.12ppb
for
zinc
pyrithione
vs.
the
agency
value
of
21.66
ppb.
When
appropriate
release
rates
and
degradation
rates
are
input
into
the
Luttik­
Johnson
model,
it
gives
a
PEC
of
0.16
ppb
,
which
is
orders
of
magnitude
lower
than
the
21.66
ppb.

Arch
requests
that
RASSB
of
the
AD
refine
the
PEC
calculations
using
models
that
allow
incorporation
of
relevant
multiple
environmental
parameters
(
e.
g.
EXAMS,
MAM­
PEC).
Arch
modelers
have
done
this
exercise
and
the
data
are
presented
below
(
Table
3)
for
consideration.

Validation
of
exposure
modeling
may
only
be
done
by
comparison
of
PEC
values
with
measured
environmental
concentrations.
Despite
some
monitoring
activity,
zinc
pyrithione
has
not
been
detected
in
the
environment.
For
this
reason,
methods
used
to
calculate
the
PEC
of
zinc
pyrithione
cannot
be
corroborated
by
measured
concentrations.
As
an
alternative,
Arch
has
applied
the
zinc
pyrithione
modeling
approach
to
calculate
the
PEC
of
a
widely
used,
persistent
antifouling
biocide
Irgaol),
for
which
extensive
monitoring
data
is
available.
Using
MAM­
PEC
and
EXAMS,
PEC
values
for
Irgarol
1051
were
calculated
to
be
1.3
and
3.4
µ
g/
L,
respectively.
These
are
in
agreement
with
the
highest
measured
Irgarol
concentrations
of
2.1
µ
g/
L
(
Danish
marinas).
We
are
therefore
confident
that
our
modeling
approach
provides
realistic
PEC
values.

The
Agency
PEC
value
of
21.66
µ
g/
L
for
zinc
pyrithione
is
10­
fold
higher
than
the
highest
measured
environmental
concentration
(
2.1
µ
g/
L)
of
Irgarol
in
a
real
worstcase
marina.
It
is
difficult
to
rationalize
a
scenario
where
the
concentration
of
a
biocide
with
a
short
half­
life
could
exceed
the
concentration
of
a
persistent
biocide
having
comparable
market
share.
Arch's
method
not
only
generates
PEC
values
that
are
more
consistent
with
the
relative
persistence
of
Irgarol
and
pyrithione,
but
it
is
also
consistent
with
measured
environmental
concentrations
of
Irgarol.

Therefore,
Arch
requests
the
Agency
to
refine
or
redefine
its
modeling
approach
and
PEC
calculations
for
zinc
pyrithione
recognizing
that
 
in
the
absence
of
validated
laboratory
methods
(
since
the
ASTM
leach
rate
method
over­
estimates
the
leach
rates),
release
rates
can
be
calculated
from
mass
balance/
service
life
data
for
current,
commercial
paints
 
biocides
like
other
chemicals
undergo
abiotic
and
biotic
transformations
in
the
environment
­
biodegradation
and
photolysis
data
from
guideline
studies
that
have
been
reviewed
and
accepted
should
be
considered.
 
more
sophisticated
multi­
fate
models
such
as
EXAMS,
MAM­
PEC
or
REMA
are
more
appropriate
for
modeling
biocides
that
degrade
by
multiple
pathways.
 
calculated
PEC
values
should
be
compared
with
measured
environmental
concentrations
as
a
reality
check,
using
a
surrogate
antifoulant
if
necessary.
If
the
PEC
values
are
significantly
higher
than
actual
environmental
concentrations,
it
should
be
realized
that
there
is
a
strong
bias
in
the
modeling
approach
and
the
resulting
PEC
should
not
be
used
to
carry
out
risk
assessments
of
either
persistent
or
non­
persistent
antifouling
biocides.
9
The
significance
of
using
the
appropriate
leach
rate
and
appropriate
degradation
rate
are
highlighted
in
the
tables
below.

Significance
of
Leach
rate
data
Table
1.
ASTM
laboratory
leach
rates
from
paints
formulated
with
zinc
pyrithione
(
from
MRID
45821001,
Table
VII,
p.
56)

Paint
Leach
Rate
(
µ
g/
cm2/
day)
Period
%
ZnPT
MRID
Ecoloflex
BEA369
Self­
polishing
cuprous
oxide
based
large
vessel
6.5
±
0.9
5.1
days
21­
49
day
49
3.8
44877104
Ecoloflex
BEA468
Self­
polishing
cuprous
oxide
based
large
vessel
5.4
±
0.8
3.9
days
21­
49
day
49
3.8
44877105
Ecoloflex
BEA469
­
Selfpolishing
cuprous
oxide
based
large
vessel
4.3
±
0.7
3.2
days
21­
49
day
49
3.8
44877106
Ecoloflex
BEA368
Self­
polishing
cuprous
oxide
based
paint
for
large
vessels
7.2
±
1.1
5.9
days
21­
49
day
49
3.8
44877103
Ablative
zinc
oxide
based
resin/
wood
rosin
paint
for
aluminum
hulls
7.2
±
1.1
5.4
days
21­
45
day
45
2.4
43864603
Long­
life
cuprous
oxide
based
paint,
Vinyl
Red
naval
formula
121
2.3
±
0.5
1.9
days
21­
45
day
45
5.9
43864603
E.
Paint
SN­
1
Ablative
zinc
oxide
solventbased
paint
1.24
±
0.23
1.01
days
22­
49
day
49
2
44833310
E.
Paint
EP2000
Ablative
zinc
oxide
waterbased
paint
2.02
±
0.72
1.12
days
22­
49
day
49
4.7
44833310
10
Table
2.
Environmental
rate
constants
for
zinc
pyrithione
MRID
45821001
Degradation
Pathway
Rate
Constant
day­
1
Half­
life
Guideline
MRID
Statusa
Abiotic
Hydrolysis
<
0.0072
>
90
d
161­
1
43864602
A
Photolysis
Indoor
Outdoor
57.0
 
76.8
266
­
561
13
 
17.5
min
1.8
 
3.8
min
161­
2
supplemental
44011501
45821001
A
NR
Biotic
Water
column
biolysis
0.17
 
2.3
7.2
 
96
hr
supplemental
45821001
NR
Sediment­
catalyzed
deg
28
­
33
0.5
 
0.6
hr
162­
3
162­
3
44850003
44850004
A
A
Sediment­
sorbed
deg
0.17
­
0.87
18
 
96
hr
162­
3
162­
4
448500014
4850002
A
A
Microcosm
Dark­
dosed
Light­
dosed
>
1.4
28
<
12
hr
0.6
hr
supplemental
supplemental
45876501
45876501
NR
NR
a.
A
is
accepted;
NR
is
not
reviewed
Table
3.
PECs
for
EPA
marina
scenario
calculated
by
4
aquatic
exposure
models
for
zinc
pyrithione
and
Irgarol
1051
vs.
monitored
concentrations,
MRID
45821001
Predicted
environmental
concentrations,
µ
g/
L
Monitored,
µ
g/
L
concentrations,
ug/
L
Co­
biocide
EXAMS
MAMPEC
Luttik­
Johnson
Tidal
Prism
Highest
reported
Country
Zinc
Pyrithione
0.12
0.12
0.11
0.16
0.16
0.099
<
0.020
nd
U.
K.
a
<
2.0
nd
Japanb
Irgarol
1051
3.4
1.3
3.7
3.7
2.1
Denmarkc
1.42
U.
K.
a
1.7
Franced
0.64
Francee
a
Thomas
et
al,
2001;
Appendix
A
in
MRID
45821001;
b
Yasuba,
2000;
Morita,
2001;
c
Århus
A.,
1997;
d
Readman
et
al,
1993;
e
Tolosa
et
al,
1996
11
Arch
has
also
supplied
PEC
values
using
either
EXAMS
or
MAM­
PEC
to
various
international
regulatory
bodies
and
registrations
have
been
approved
for
several
countries.
The
modeling
approach
in
Table
4
used
realistic
environmental
scenarios
and
lab
leach
rate
data
generated
from
several
commercial
antifoulant
paints
and
the
PEC
values
(
0.001
to
0.06
ppb)
generated
from
such
realistic
scenarios
are
orders
of
magnitude
lower
than
21.66
ppb.

Zinc
OMADINE

is
now
registered
for
antifoulant
use
in
UK,
Malta,
Ireland,
Hong
Kong,
Australia,
New
Zealand,
Sweden,
Switzerland,
Finland,
Holland,
Belgium,
Japan,
S.
Korea,
and
China.

Table
4.
Arch
submission
to
other
Regulatory
Bodies:
Calculated
PECs
(
µ
g/
L;
ppb)
using
EXAMS
or
MAM­
PEC
Agency
Scenario
PEC,
(
µ
g/
L;
ppb)

Finland
 
SYKE
Spring,
Summer,
Fall
Typical
Finnish
Marina
0.045
Typical
Finnish
Harbor
0.0002
Worst
Case
Harbor
0.011
Sweden
 
KemI
June­
July
0.001
Fiskebackskil
marina
0.021,
0.061
Australia
Harbor
0.007
Lake
Geneva
0.001
Switzerland
Feb,
­
Nov.
Swiss
Marina
0.027
Netherlands
 
CTB
Fiskebackskil
parameters
0.06
EPA
Response:

EPA
has
now
incorporated
the
antifoulant
leaching
studies
into
the
Environmental
Fate
Chapter
(
N.
Shamim
April
2004),
and
used
these
data
to
revise
the
predicted
environmental
concentrations
(
PECs).
The
leaching
studies
submitted
by
the
registrant
have
been
reviewed
and
accepted
by
AD,
and
Data
evaluation
records
(
DERs)
have
been
written.
The
revised
PECs
range
from
0.0144
to
0.101
ppb
based
on
the
MAM­
PEC
model.

The
microcosm
study
was
reviewed
and
added
to
the
Environmental
fate
chapter.
Below
is
a
brief
summary
of
the
Agency's
review
of
the
Zinc
Pyrithione
Outdoor
Microcosm
Study
(
MRID
45876501):

This
was
submitted
by
the
registrants
and
reviewed
by
the
Agency,
although
it
was
not
a
required
study.
The
study
report
states
that
it
was
conducted
using
OPPTS
Guideline
835.3180
as
guidance;
however,
the
study
does
not
fully
meet
the
Guideline
requirements.
OPP
is
retaining
the
study
as
supplemental
information
on
the
degradation
of
zinc
pyrithione
under
simulated
12
natural
conditions.
The
results
of
the
study
indicate
that
pyrithione,
added
to
seawater
in
a
manner
to
simulate
leaching
from
treated
vessels,
degrades
rapidly
and
essentially
completely
within
24
hours,
regardless
of
the
time
of
day
or
night
that
leaching
occurs.
The
half­
life
of
zinc
pyrithione
in
the
light­
dosed
tank
was
36
minutes,
while
the
half­
life
in
the
dark­
dosed
tank
was
estimated
to
be
approximately
20
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.
The
results
of
those
studies
will
be
incorporated
into
the
revised
modeling
for
the
antifoulant
use
during
the
reassessment
of
the
conditional
registration
of
antifouling
products.

Although
the
study
was
conducted
as
a
microcosm
study,
it
does
not
address
the
ecological
effects
parameters
which
would
typically
be
addressed
in
OPPTS
Guideline
850.1950,
Field
Testing
for
Aquatic
Organisms
(
e.
g.,
actual
toxic
effects
on
aquatic
organisms
of
various
taxa,
usually
conducted
as
a
microcosm
or
mesocosm
study).
Such
field
testing
is
not
presently
required
for
zinc
pyrithione.

Registrant
Comment:

I.
Residential
(
Non­
Occupational)
Exposure
&
Risk,
page
5,
2nd
bullet
states
"
residential
handlers
that
paint
using
a
brush
(
antifoulant
paint
use
for
all
boat
sizes:
Dermal
MOE
=
22­
120)."

This
statement
should
be
stricken
and
the
following
should
be
considered.

Comment:
Since
1994,
the
Health
and
Safety
Executive
(
HSE)
of
the
UK
has
gathered
information
on
human
exposure
to
antifouling
products
in
the
professional
and
amateur
(
residential;
non­
occupational)
sectors 
the
surveys
and
studies
were
as
follows:

9
surveys
applying
copper­
based
antifoulant
to
ships
(
40
exposure
data;
1994)
5
surveys
applying
tin­
based
antifoulants
to
ships
(
20
exposure
data;
1996)
4
surveys
applying
various
antifoulant
to
ships
(
10
exposure
data;
IOM
1996)
8
surveys
applying
various
antifoulant
to
leisure
craft
(
9
exposure
data;
1997­
99)

This
information
was
utilized
in
providing
exposure
data
for
HSE
to
conduct
a
risk
assessment
that
covered
professional
and
amateur
applicators
of
antifoulant
paint
that
contained
zinc
OMADINE

.
The
assumptions
that
were
used
were:
4%
active
substance
in
the
product;
1%
dermal
penetration
value;
and
4%
or
1%
clothing
penetration.

Based
on
this
assessment,
HSE
came
up
with
a
central
tendency
and
worst
case
exposure
for
each
application
i.
e.,
professional
application
with
brush/
roller
and
amateur
application
with
brush/
roller.
The
HSE
uses
Toxicity
Exposure
Ratios
(
TERs)
which
are
analogous
to
USEPAs
MOEs.
For
amateur
application
using
a
13
brush/
roller
the
central
tendency
for
systemic
exposure
(
excluding
inhalation)
was
500
and
for
inhalation
the
TER
was
17500.
The
worst
case
exposure
for
amateur
using
brush/
roller
for
systemic
exposure
was
TER
of
6.
However,
the
central
tendency
represents
the
mean
exposures
and
is
based
on
actual
field
data
for
applying
antifoulant
paints
and
may
prove
useful
for
the
USEPA.
Especially,
since
the
USEPA
has
indicated
that
data
was
extrapolated
from
the
PHED
database
and
has
indicated
that
the
confidence
in
the
PHED
data
is
C
and
is
not
based
on
actual
application
of
antifoulant
paints.
Reference
for
some
of
the
HSE
Surveys:
Garrod,
A.
N.
I.,
Guiver,
R.,
and
Rimmer,
D.
A.
Potential
Exposure
of
Amateurs
(
Consumers)
Through
Painting
Wood
Preservative
and
Antifoulant
Preparations.
Am.
Occup.
Hyg.
Vol
44,
No.
6:
421­
426,
(
2000)

EPA
Response:
The
Agency
has
reviewed
the
Garrod
et
al.
2000
study,
and
concluded
that
only
the
inhalation
exposure
data
are
of
sufficient
quality
for
inclusion
into
the
risk
assessment.
A
Data
Evaluation
Record
(
DER)
for
this
study
has
been
prepared,
see
memo
from
T.
Leighton,
D301375,
April
2004.
The
data
from
this
study
were
used
to
supplement
the
current
exposure
and
risk
estimates
from
PHED.
Based
on
this
study,
the
Agency
estimated
a
mean
inhalation
unit
exposure
(
UE)
of
0.00087
mg/
m3/%
ai
and
MOEs
ranging
from
5­
140,
depending
on
the
boat
size,
duration
of
painting
time
(
2,4
or
6
hours),
and
percent
ai,
where
both
EPA
Reg.
No.
2693­
194
(
47
percent
ai)
and
EPA
Reg.
No.
64684­
4
(
4.8
percent
ai)
were
evaluated.

Registrant
Comment:

J.
Residential
(
Non­
Occupational)
Exposure
&
Risk,
page
5,
last
sentence
before
"
Aggregate
Exposure
and
Risk",
states,
"
The
estimated
dermal
MOE
is
3,300
based
on
conservative
assumptions,
and
the
results
of
a
study
that
measured
concentrations
of
zinc
OMADINE

in
the
urine
for
5
days
following
a
single
shampoo
application.

Should
read,
"
The
estimated
dermal
MOE
is
3,300
based
on
conservative
assumptions,
and
the
results
of
a
study
that
measured
radioactivity
associated
with
metabolized
zinc
OMADINE

in
the
urine
for
5
days
following
a
single
shampoo
application
containing
radiolabelled
zinc
OMADINE

.

Comment:
Radioactivity
was
measured,
not
the
zinc
OMADINE

.
The
radioactivity
was
from
metabolized
zinc
OMADINE

.

EPA
Response:
The
suggested
change
was
made.

Registrant
Comment:

K.
Aggregate
Exposure
&
Risk,
Acute,
Page
5,
last
sentence
" 
acute
PEC
of
21.66
ppb":

Should
read
" 
acute
PEC
of
0.12
ppb "
14
Comment:
See
discussion
under
"
H"
above.

EPA
Response:
The
PEC
was
revised
based
on
the
MAM­
PEC
model.
The
Agency
estimated
a
range
of
PECs
of
0.0144
to
0.101
ppb,
based
on
a
range
of
leaching
rates.

Registrant
Comment:

L.
Aggregate
Exposure
&
Risk,
Oral,
Page
6,
states
"
The
short­
and
intermediate­
term
oral
aggregate
risk
for
adult
males
and
females
do
not
exceed
the
Agency's
level
of
concern.
However,
the
DWLOC
for
infants/
children
of
17
ppb
is
slightly
less
than
the
PEC
of
21.66
ppb,
indicating
a
potential
for
adverse
risks
of
concern ".

Should
read
"
The
short­
and
intermediate­
term
oral
aggregate
risks
for
all
population
groups
do
not
exceed
the
Agency's
level
of
concern
with
a
lower
PEC
of
0.12
ppb."

Comment:
See
discussion
under
"
H"
above.

EPA
Response:
The
conclusions
were
modified
based
on
the
revised
PEC
for
zinc
omadine.
All
aggregate
risks
via
the
oral
route
of
exposure
are
below
the
Agency's
level
of
concern.

Registrant
Comment:

M.
Aggregate
Exposure
&
Risk,
Dermal
&
Inhalation,
Page
6,
in
both
of
the
Dermal
and
Inhalation
sections
the
author
indicates
that
due
to
the
fact
that
the
dosing
for
the
Dermal
90­
day
study
were
log
doses
and
the
MOEs
exceeded
the
level
of
concern
(
LOC)
and
these
MOEs
were
based
on
subchronic
toxicity
and
doses
were
based
on
whole
body
exposures
and
a
large
gap
between
the
NOEL
and
LOEL
existed
for
the
Dermal
study
indicated
that
the
evaluation
was
very
conservative.

Guidance
requested:
This
verbiage
suggested
the
need
for
shorter
exposures
etc.
e.
g.
5­
day
dermal
study
with
evaluation
of
doses
between
100
and
1000
mg/
kg/
day
and
the
same
for
Inhalation
toxicity
looking
at
higher
doses
for
a
nose­
only
5­
day
exposure
period
instead
of
a
90­
day
whole
body
subchronic
exposure.
We
request
verification
that
conducting
5­
day
dermal
and
5­
day
inhalation
studies
would
be
useful
for
assessing
the
hazard
for
paints.

EPA
Response:
No
change
necessary.
No
additional
toxicity
studies
are
requested
at
this
time.
This
language
was
provided
as
part
of
risk
characterization.

Registrant
Comment:

N.
Aggregate
Exposure
&
Risk,
Chronic,
Page
7,
3nd
sentence
"
However
for
infants/
children,
the
DWLOC
of
15
ppb
is
slightly
less
than
the
PEC
of
21.66
ppb,
indicating
the
potential
for
aggregate
chronic
risks
of
concern"
15
Should
be
stricken
or
modified
to
have
no
potential
for
concern
because
the
acute
PEC
is
0.12
ppb "

Comment:
See
discussion
under
"
H"
above.

EPA
Response:
The
conclusions
were
modified
based
on
the
revised
PEC
for
zinc
omadine.
All
aggregate
risks
via
the
oral
route
of
exposure
are
below
the
Agency's
level
of
concern.

Registrant
Comment:

O.
Occupational
Exposure
and
Risk,
page
8,
third
bullet
reads,
"
handling
zinc
OMADINE

­
containing
paint
products
using
an
airless
sprayer
application
method
(
inhalation
MOEs
=
4.4
and
44
with
and
without
the
use
of
a
respirator
as
PPE,
respectively,
and
dermal
MOE
=
74
without
the
use
of
gloves
as
PPE)."

Should
read:
"
handling
zinc
OMADINE

­
containing
paint
products
using
an
airless
sprayer
application
method
(
inhalation
MOEs
=
44
and
4.4
with
and
without
the
use
of
a
dust
mask
as
PPE,
respectively,
and
dermal
MOE
=
74
without
the
use
of
gloves
as
PPE)."

Comment:
For
professional
applicators,
use
of
NIOSH/
MSHA
approved
respirator
(
half
or
full
face)
commonly
provide
50
to
100%
reduction
in
exposures.

EPA
Response:
No
change
was
made.
The
Agency
assumes
that
the
use
of
an
organic­
vapor
respirator
provides
approximately
a
90%
protection
factor,
which
was
used
in
the
risk
assessment.
The
Agency
assumes
that
a
dusk
mask
would
provide
approximately
80%
protection
factor.
Risks
would
still
be
of
concern
for
a
dust
mask
.

Registrant
Comment:

P.
Environmental
Risk,
Environmental
Fate
page
9,
3rd
sentence,
"
Half­
lives
in
buffered
water
were
measured
at
99,
120
and
123
days
at
pHs
5,7,
and
9
respectively.
In
sea
water,
the
half
life
was
96
days"

Should
read:
"
Half­
lives
in
buffered
water
were
extrapolated
from
30
day
studies
to
give
99,
120
and
123
days
at
pHs
5,7,
and
9
respectively.
In
sea
water,
the
extrapolated
half
life
was
96
days".

EPA
Response:
The
language
was
revised
to
address
this
comment.
16
Registrant
Comment:

Q.
Environmental
Risk,
Environmental
Fate,
page
9,
4th
sentence,
"
These
half­
lives
indicate
that
zinc
OMADINE

can
be
persistent
in
water
under
conditions
of
low
microbial
activity."

This
sentence
should
be
omitted
since
it
incorrectly
implies
that
the
degradation
of
zinc
pyrithione
is
solely
dependent
upon
microbial
activity.
Degradation
also
occurs
by
photolysis
and
sediment­
catalyzed
chemical
reactions.

EPA
Response:
The
language
was
revised
to
address
this
comment.
The
environmental
fate
chapter
has
been
revised
based
on
additional
studies
submitted
by
the
registrant.
Accordingly,
the
environmental
fate
assessment
section
had
been
rewritten.

Registrant
Comment:

R.
Environmental
Risk,
Environmental
Fate
page
9,
7th
and
8th
sentence,
"
In
aerobic
aquatic
media,
the
half­
lives
of
zinc
OMADINE

were
12.4
and
15
days
for
fresh
water
and
sea
water
respectively.
In
the
same
media,
the
half­
lives
under
anaerobic
conditions
are
25
and
13.3
hours,
respectively".

Should
read,
"
In
aerobic
aquatic
media,
degradation
was
biphasic
with
t
½
 
=
30­
90
min
for
freshwater
and
seawater
and
t
½
 
=
4­
15
days
for
seawater
and
15
days
for
freshwater.
In
the
same
media,
degradation
under
anaerobic
conditions
was
also
biphasic
with
t
½
 
=
30
min
for
freshwater
and
seawater
and
t
½
 
=
25
hours
for
fresh
water
and
13.3­
19
hours
for
seawater."

Comment:
Data
from
accepted
guideline
studies
was
omitted
so
that
range
of
half­
lives
is
not
accurate
(
MRID#
s
44850002,
44010401).
The
half­
life
values
given
are
from
aerobic
and
anaerobic
aquatic
metabolism
studies
done
in
water/
sediment
at
3­
ppm
(
MRID#
44010403).
These
studies
showed
degradation
in
two
distinct
phases:
an
initial
rapid
rate
of
decline,
during
which
~
50%
(
aerobic)
to
~
80%
(
anaerobic)
of
the
pyrithione
degraded
over
a
period
of
1­
2
hours,
followed
by
a
slower
rate
of
decline
in
the
sediment.
Only
the
longer
second
phase
half­
lives
are
cited.
However,
the
second
phase
half­
lives
were
shown
to
be
largely
the
result
of
the
conversion
of
zinc
pyrithione
to
copper
pyrithione
by
reaction
with
copper
in
the
sediment.
Degradation
of
the
sequestered
copper
pyrithione,
which
is
soluble
only
to
the
extent
of
0.1
ppm,
is
inhibited
by
its
precipitation
from
solution
at
the
high
dose
level.

It
is
therefore
not
appropriate
to
use
the
second­
phase
half
lives
from
these
studies.

Subsequent
aerobic
and
anaerobic
studies
done
with
zinc
pyrithione
and
copper
pyrithione
at
lower
concentrations
have
been
submitted
and
accepted
by
the
agency
17
(
MRID#
s
44850002).
These
studies
were
conducted
at
a
concentration
of
50
ppb
(
this
concentration
was
chosen
to
allow
detection
of
pyrithione
with
the
existing
analytical
methods;
even
though
the
expected
environmental
concentrations
are
still
orders
of
magnitude
lower),
which
is
below
the
solubility
of
copper
pyrithione.
Degradation
was
biphasic
in
these
studies
as
well;
however,
the
second
phase
of
decline
was
much
faster.
The
biphasic
degradation
at
the
lower
concentration
is
attributed
to
the
high
affinity
of
pyrithione
for
sediment.
In
the
aerobic
system,
the
half
lives
for
removal
of
pyrithione
from
water
and
from
sediment
was
0.024
days
and
4.0
days,
respectively.
In
the
anaerobic
system,
the
corresponding
values
were
0.020
days
and
0.79
days.
For
the
water
and
sediment
combined,
dissipation
times
were
0.89
days
for
50%
and
34
days
for
90%
in
the
aerobic
system
and
0.02
days
for
50%
and
0.79
days
for
90%
in
the
aerobic
system.
The
degradation
of
zinc
pyrithione
and
copper
pyrithione,
as
well
as
the
formation
and
decline
of
the
metabolites,
is
identical.
Based
on
the
more
recent
studies
done
at
50
ppb,
the
half
lives
for
pyrithione
is
1­
2
hours
in
water
and
1­
4
days
in
sediment.

EPA
Response:
The
Environmental
fate
chapter
has
been
rewritten
and
changes
have
been
incorporated
into
the
revised
risk
assessment.

Registrant
Comment:

S.
Environmental
Risk,
page
9,
6th
sentence,
"
Photolytic
measurements
showed
that
zinc
OMADINE

dissociates
in
13
minutes
in
buffered
medium "

Should
read,
"
Photolytic
measurements
showed
that
zinc
OMADINE

degrades
in
13
minutes
in
buffered
medium "

EPA
Response:
This
change
has
been
made
in
the
environmental
fate
chapter
and
risk
assessment.

Registrant
Comment:

T.
Environmental
Risk,
page
9,
2nd
paragraph,
2nd
sentence,
"
The
octanol/
water
partition
coefficient
is
less
than
1000,
which
makes
it
unlikely
to
bioaccumulate,
although
with
its
high
Kds
for
sediments
and
a
long
hydrolytic
half­
life,
it
can
be
persistent
in
soils
and
sediments
containing
little
or
no
microbial
population".

Should
read
"
The
octanol/
water
partition
coefficient
is
less
than
1000
(
log
Kow
=
0.97,
which
makes
it
unlikely
to
bioaccumulate."

The
remainder
of
the
sentence
referring
to
persistence
in
soils
and
sediments
containing
little
or
no
microbial
population
is
not
correct
and
should
be
omitted.
18
EPA
Response:
The
text
was
revised
to
address
this
comment.

Registrant
Comment:

U.
Environmental
modeling/
Exposure,
page
10
states
"
The
boat
antifoulant
use,
however,
is
expected
to
produce
significant
exposure
to
aquatic
organisms,
and
environmental
modeling
was
conducted
to
assess
the
exposure
and
risk
from
this
use"

Should
read:
"
The
boat
antifoulant
use,
however,
is
expected
to
produce
low
exposure
to
aquatic
organisms,
and
appropriate
and
refined
environmental
modeling
should
be
conducted
to
assess
the
exposure
and
risk
from
this
use"

Comment:
Refer
to
the
previous
discussion
in
section
H
of
the
refined
modeling
that
includes
more
accurate
leach
rate
data
and
multiple
degradation
rates
that
clearly
demonstrates
significantly
lower
PEC
values
than
what
AD
generated
using
the
Luttik­
Johnson
model.

EPA
Response:
The
predicted
environmental
concentrations
(
PECs)
for
the
antifoulant
paint
use
have
been
revised
based
on
previous
comments
and
using
the
MAM­
PEC
model.
The
ecological
risks
associated
with
the
conditionally
registered
antifoulant
paint
use
have
been
removed
from
this
risk
assessment
and
will
be
evaluated
upon
submission
of
the
requested
ecotoxicity
studies.

Registrant
Comment:

V.
Ecological
Hazard
and
Risk,
page
10,
1st
paragraph
states
"
The
antifoulant
use
of
zinc
OMADINE

is
likely
to
result
in
adverse
acute
and
chronic
effects
to
fish
and
aquatic
invertebrates,
including
endangered
species.
It
also
causes
adverse
impacts
on
freshwater
and
marine
invertebrate
reproduction
and
growth
at
very
low
levels.
These
reproductive
impacts
indicate
that
zinc
OMADINE

is
a
potential
endocrine
disruptor."

Arch
respectfully
disagrees
with
these
statements.
and
recommends
that
they
be
and
be
replaced
with
.
"
The
anitfoulant
use
of
zinc
OMADINE

is
unlikely
to
result
in
adverse
effects
to
fish
and
aquatic
invertebrates
based
on
the
refined
PEC
values
of
0.12
ppb.
Zinc
OMADINE

at
near
lethal
concentrations
(
i.
e.
at
or
near
the
LC50
values
reported
for
fish
and
invertebrates)
was
observed
to
produce
limited
effects
to
reproduction
and
minor
effects
to
growth
thus
diminishing
the
concern
for
potential
endocrine
disruption."

Comment:
a)
If
the
phrase
`
likely
to
result'
is
based
on
a
PEC
of
21.66
ppb,
then
it
should
be
recognized
that
this
number
came
from
a
preliminary
risk
assessment
that
needs
further
refinement,
particularly
since
it
is
ten­
fold
higher
than
measured
concentrations
of
widely
used
antifouling
biocides
that
are
persistent
as
discussed
in
19
earlier
comments
(
in
section
H).
Efforts
to
detect
zinc
pyrithione
in
marinas
have
been
unsuccessful
to
date
(
MRID#
45821001;
Table
3).
The
detectabilities
of
the
monitoring
methods
were
well
below
aquatic
toxicity
levels.
Therefore
the
above
conclusion
of
"
likely
to
result
in
adverse
acute
and
chronic
effects"
would
appear
to
be
based
on
a
hazard
assessment
from
erroneous
data
rather
than
a
refined
risk
assessment.

Comment
b):
The
results
from
testing
zinc
OMADINE

in
the
Early
Life
Stage
Study
of
the
fathead
minnow
resulted
in
a
NOEC
of
1.22
µ
g/
L
following
32­
days
of
exposure
with
a
LOEC
of
2.82
µ
g/
L.
The
sensitive
toxic
endpoints
were
survival
and
sublethal
effects
at
hatch
and
days
7,
14,
21,
and
28
post
hatch.
There
was
no
apparent
effect
on
reproduction
but
in
the
AD
Preliminary
Risk
Assessment
there
is
mention
of
developmental
effects
to
the
fish
i.
e.
bent
bodies.
This
effect
only
was
observed
at
concentrations
above
1.22
µ
g/
L
( 
2.82
µ
g/
L)
and
only
became
visible
on
days
5­
10
and
again
on
days
17­
32
post
hatching,
strongly
suggesting
that
repeated
exposures
to
near
lethal
concentrations
of
zinc
OMADINE

was
responsible
for
this
effect
and
not
developmental
toxicity.
NOTE:
The
Acute
LC50
in
fathead
minnow
for
zinc
Omadine
®
is
2.68
µ
g/
L
(
see
table
13
page
42
of
the
AD
Preliminary
Risk
Assessment).
The
results
from
testing
zinc
OMADINE

in
the
Chronic
Toxicity
to
the
Daphnid,
Daphnia
magna
with
Zinc
OMADINE

demonstrated
that
the
NOEC
is
2.7
µ
g/
L
and
the
LOEC
is
5.8
µ
g/
L.
Doses
tested
were
0,
2.7,
5.8,
12,
22,
and
49
µ
g/
L.
The
LC50
for
Daphnid
reported
in
the
AD
Preliminary
Risk
Assessment
is
8.25
µ
g/
L.
The
mean
day
to
the
first
brood
was
delayed
at
22
and
49
µ
g/
L,
concentrations
that
clearly
produce
significant
toxicity
to
the
Daphnid.
At
concentrations
of
12
and
22
µ
g/
L
lengths
were
affected
(
however,
differences
in
length
never
achieved
statistical
significance;
no
animals
survived
to
day
32
at
49
µ
g/
L),
again
concentrations
of
zinc
OMADINE

causing
an
effect
to
length
also
are
producing
significant
toxicity
i.
e.
LC50
8.25
µ
g/
L
(
significant
mortality
was
observed
at
49
µ
g/
L
starting
on
day
2
with
near
100%
mortality
by
day
6).

The
Chronic
Toxicity
of
Zinc
OMADINE

to
the
Mysid,
Americamysis
bahia
resulted
in
a
NOEC
of
2.28
µ
g/
L
and
a
LOEC
of
4.20
µ
g/
L.
The
LC50
for
Mysid
is
4.7
µ
g/
L
as
reported
in
the
AD
Preliminary
Risk
Assessment.
At
concentrations
of
zinc
OMADINE

that
allowed
survival
equal
or
similar
to
control
values,
no
reproductive
effects
were
observed.
Zinc
OMADINE

appears
to
be
more
of
an
acute
hazard
over
a
chronic
hazard,
based
on
review
of
the
acute
LC50/
NOEC
and
chronic
LOEC/
NOEC
values.
The
chronic
NOEC
values
are
in
every
case
similar
to
the
acute
NOEC
values.
The
fact
that
only
doses
of
zinc
OMADINE

that
were
near
or
greater
than
the
corresponding
LC50
were
resulting
in
effects
in
reproduction
etc.
strongly
argues
against
any
chronic
hazard
and
definitely
confounds
any
interpretation
of
possible
endocrine
disruption.

We
agree
that
as
the
agency
states,
"
when
appropriate
screening
methods
have
been
developed,
ZPT
will
be
tested
against
those
protocols".
20
EPA
Response:
The
ecological
risks
associated
with
the
conditionally
registered
antifoulant
paint
use
have
been
removed
from
this
risk
assessment
and
will
be
evaluated
upon
submission
of
the
requested
ecotoxicity
studies.

Registrant
Comment:

W.
Ecological
Hazard
and
Risk,
page
10,
3rd
paragraph,
entire
paragraph
 
acute
and
chronic
LOCs
have
been
exceeded"

This
paragraph
should
be
stricken
because
this
is
an
incorrect
conclusion
based
on
an
incorrect
PEC
calculation
(
see
section
H).

Comment:
As
discussed
previously
in
section
H,
the
exposure
modeling
was
a
preliminary
risk
assessment
that
needs
further
refinement,
particularly
since
it
is
tenfold
higher
than
measured
concentrations
of
widely­
used
antifouling
biocide,
e.
g.
Irgarol,
that
is
persistent.
If
the
modeling
is
refined
using
the
proper
parameters
for
leach
rate
and
degradation
(
see
section
H,
Table
3
and
4),
the
PEC
will
be
a
factor
of
10
to
a
1000
less
than
the
NOEC
of
the
most
sensitive
aquatic
organisms.
These
refined
PECs
will
not
exceed
the
LOCs.

EPA
Response:
The
ecological
risks
associated
with
the
conditionally
registered
antifoulant
paint
use
have
been
removed
from
this
risk
assessment
and
will
be
evaluated
upon
submission
of
the
requested
ecotoxicity
studies.

Registrant
Comment:

X.
Section
2.0,
Physical
&
Chemical
Properties,
page
11
listing
of
properties,
"
Kow
0.97
@
25
deg.
C":
Should
read
"
log
Kow
0.97"
"
Koc
2000­
3500"
Should
read
"
log
Koc
2.9­
4.0"

EPA
Response:
This
suggested
change
was
made.

Registrant
Comment:

Y.
Section
2.0,
Physical
&
Chemical
Properties,
page
11,
2nd
sentence,
"
However,
it
is
fairly
stable
in
fresh
water
and
sea
water
under
conditions
of
low
microbial
activity."

Should
read,
"
However,
it
is
fairly
stable
in
filtered
sterile
fresh
water
and
sterile
sea
water
in
the
absence
of
light."
21
Comment:
There
are
no
instances
of
marinas
and
harbors
that
we
are
aware
of
that
have
little
to
no
microbial
activity
.
The
marinas
and
harbors
are
very
rich
in
microbial
populations
that
would
readily
degrade
any
leached
zinc
OMADINE

.

EPA
Response:
The
Environmental
Fate
chapter
has
been
rewritten
based
on
additional
studies/
data
provided
by
the
registrant.
The
risk
assessment
was
also
revised
to
reflect
this
change.

Registrant
Comment:

Z.
Section
2.0,
Physical
&
Chemical
Properties,
page
11,
last
sentence,
" 
it
can
be
persistent
in
soils
and
sediments
containing
little
or
no
microbial
population."

Should
read:
" 
it
is
not
persistent
in
soils
containing
little
or
no
microbial
population,
since
it
is
degraded
by
sediment
as
well
as
by
redox
pathways"

Comment:
The
Agency
makes
an
incorrect
conclusion
about
degradation
depending
solely
on
the
presence
of
microbes.
The
aerobic
and
anaerobic
aquatic
metabolism
studies
both
showed
biphasic
degradation
with
a
sediment­
catalyzed
term
that
has
a
30
minute
half­
life,
consistent
with
a
chemical
reaction
and
inconsistent
with
microbial
degradation.
The
N­
oxide
of
zinc
pyrithione
is
cleaved
by
reducing
agents
(
anaerobic
sediment).
Also
the
thiol
group
is
readily
oxidized
by
trace
metals.
It
should
also
be
noted
that
extensive
degradation
was
observed
in
other
guideline
studies
with
sediment
and
soil
(
ads/
des,
soil
leach).
These
studies
were
all
conducted
in
the
absence
of
light.
If
light
is
present,
photolysis
becomes
an
additional
important
degradation
pathway.

EPA
Response:
The
Environmental
Fate
chapter
has
been
revised
to
reflect
the
incorporation
of
additional
data.
The
risk
assessment
has
also
been
revised.

Registrant
Comment:

AA.
Section
3.0,
Hazard
Characterization,
Developmental
Toxicity,
page
12,
1st
paragraph,
"
Developmental
toxicity
studies
using
the
oral
route
of
administration
show
zinc
OMADINE

to
produce
significant
developmental
effect
in
rabbits
which
are
greater
in
severity
at
doses
of
1.5
and
3.0
mg/
kg/
day
than
toxicity
observed
in
maternal
animals
at
these
same
dose
levels."

Should
read:
"
No
developmental
effects
were
observed
at
concentrations
below
1.5
mg/
kg/
day
and
severe
maternal
toxicity
was
observed
at
1.5
and
3.0
mg/
kg/
day
22
Comment:
In
section
3.0
Hazard
Characterization
the
reference
to
endocrine
disruption
is
associated
with
the
agencies
concern
for
the
potential
of
zinc
OMADINE

to
cause
developmental
effects
based
on
the
Developmental
Toxicity
study
carried
out
in
Rabbits
with
zinc
OMADINE

.
As
mentioned
under
number
2.0
comment,
the
DER
for
the
rabbit
study
indicates
that
the
significant
decrease
in
body
weight
gain
in
the
does
at
the
mid
and
high
dose
levels
(
44%
and
99%)
was
not
biologically
relevant
as
the
evaluation
of
the
absolute
body
weights
demonstrated
only
a
modest
~
4%
and
~
6%
change
in
body
weight
over
the
entire
gestation
period
days
0­
29.
In
addition,
the
DER
stated
that
there
was
no
corresponding
decrease
in
food
consumption.
However,
in
the
same
DER
report
of
the
zinc
OMADINE

Developmental
Toxicity
Study
in
the
Rabbit
Table
3.0
Food
Consumption
shows
a
statistically
significant
decrease
in
food
consumption
for
gestation
days
6­
19.
Body
weight
gains
from
gestation
days
6­
19
achieved
statistical
significance
of
p
 
0.01
that
corresponded
to
a
decrease
in
food
consumption
of
16%
(
mid­
dose,
1.5
mg/
kg/
day)
and
23%
(
high­
dose,
3.0
mg/
kg/
day).

This
clearly
indicates
that
severe
maternal
toxicity
was
present
at
the
mid­
and
highdosed
levels
and
the
developmental
toxicity
observed
in
this
study
was
a
result
of
the
significant
maternal
toxicity
and
significant
decrease
in
food
consumption.

EPA
Response:

The
following
language
was
added
to
replace
the
language
in
question.
"
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).
"

This
language
reflects
both
the
rat
and
rabbit
developmental
studies,
and
is
consistent
with
language
in
the
ADTC
2004
and
HIARC
1999
memos,
which
were
reviewed
by
between
10
and
12
senior
toxicologists.
Maternal
toxicity
was
minimal
in
the
rat
developmental
study,
as
salivation
was
noted
in
27%
of
the
animals
at
3
mg/
kg/
day.

Registrant
Comment:

BB.
Section
3.0,
Hazard
Characterization,
Developmental
Toxicity,
page
13,
2nd
paragraph
reference
to
Developmental
Toxicity
See
Comment
in
section
AA
EPA
Response:
See
Response
in
section
AA.
23
Registrant
Comment:

CC.
Section
3.0,
Hazard
Characterization,
Chronic
Toxicity
and
Carcinogenicity,
page
14,
"
Data
on
the
carcinogenic
potential
of
sodium
OMADINE

showed
no
evidence
of
carcinogenicity,
but
one
study
was
not
tested
to
an
adequate
dose."

Should
read:
"
The
only
study
available
to
evaluate
the
carcinogenicity
of
zinc
OMADINE

was
a
non­
guideline
dietary
oncogenicity
study
carried
out
with
zinc
OMADINE

that
showed
no
evidence
of
carcinogenicity.
Data
from
two
guideline
studies
evaluating
the
potential
of
sodium
OMADINE

showed
no
evidence
of
carcinogenicity,
with
one
study
failing
to
achieve
significant
toxicity
at
the
high
dose,
other
than
irritation
at
the
site
of
administration
(
study
considered
unacceptable,
but
useful
for
risk
assessment)".

Comment:
The
Agency's
comment
is
misleading
and
suggests
that
only
one
study
was
carried
out
with
sodium
OMADINE

when
in
fact
two
cancer
studies
were
carried
out,
one
Chronic
Carcinogenicity
study
in
the
rat
via
oral
gavage
and
one
Carcinogenicity
study
in
the
mouse
via
dermal
exposure.
The
Chronic
carcinogenicity
study
was
accepted
as
core
but
the
dermal
carcinogenicity
study
in
the
mouse
was
considered
inadequate
due
to
not
achieving
a
maximally
tolerated
dose.
In
addition,
a
two­
year
dietary
carcinogenicity
study
in
rats
was
carried
out
with
zinc
OMADINE

,
this
study
was
carried
out
in
the
late
1950'
s
and
would
not
be
considered
acceptable
under
today's
standards.
However,
this
study
was
negative
for
any
increase
in
tumors
over
control
animals.
This
study
along
with
the
two
sodium
OMADINE

studies
provide
additional
confidence
that
the
pyrithione's
are
not
carcinogenic.

EPA
Response:
The
zinc
pyrithione
cancer
study
will
be
mentioned
in
the
text,
along
with
the
deficiencies.
The
two
year
rat
study
for
zinc
pyrithione
from
the
1950'
s
(
TOX
Record
003933,
Larson
1958)
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.

The
text
will
be
clarified
to
acknowledge
the
oral
and
dermal
cancer
studies
for
sodium
omadine.

Registrant
Comment:

DD.
Section
3.0
Hazard
Characterization,
Metabolism,
page
14,
last
two
sentences
"
The
above
data
do
not
adequately
characterize
the
disposition
of
zinc
OMADINE

,
as
no
dual
labeled
test
material
was
studied
.
The
data
do
suggest
less
in
vivo
dissociation
of
zinc
OMADINE

vs.
sodium
OMADINE

and
greater
retention
of
zinc
in
tissues
vs.
the
pyrithione
moiety.
24
Remove
both
sentences,
based
on
comments
below
Should
read:
"
Klaasan
utilized
14C­
ZPT
and
isotopic
65­
zinc­
PT
to
study
zinc
OMADINE

.
Klaasan's
conclusions
indicate
that
zinc
and
pyrithione
go
to
different
locations
in
the
body
and
are
eliminated
at
different
rates
and
different
routes,"

Comment:
The
work
by
Klaassan
demonstrates
that
when
zinc
pyrithione
is
administered
via
oral,
dermal,
or
intravenous
routes,
the
pyrithione
moiety
separates
from
zinc
and
distributes
differently
in
the
body.
In
fact
when
it
is
administered
orally,
a
majority
of
the
zinc
is
excreted
in
the
feces
(
Klaassan,
C.
D.
(
1976).
Absorption,
distribution,
and
excretion
of
zinc
pyridinethione
in
rabbits.
Toxicology
and
Applied
Pharmacology,
35,
pp.
581­
587.

Following
oral
gavage
of
14C­
or
65Zn­
ZPT,
the
percentage
of
administered
dose
in
each
of
the
tissues
analyzed
was
about
one­
tenth
of
those
concentrations
seen
following
i.
v.
administration.
The
concentration
of
14C
was
observed
to
be
higher
than
65Zn
levels
in
liver,
kidney,
spleen,
heart,
lung,
pancreas,
intestine,
stomach,
and
spinal
cord
but
only
by
a
small
percentage
in
most
cases.
The
concentration
of
65Zn
was
observed
to
be
higher
in
blood
and
plasma,
as
well
as
in
eye
and
muscle.
Six
hours
after
oral
administration
of
ZPT
1.35%
of
the
14C
and
4.4%
of
the
65Zn
was
found
in
the
major
organs.
The
14C
levels
in
the
blood
were
observed
to
decrease
between
2
and
6
hours
where
levels
of
65Zn
were
observed
to
be
on
the
increase.
Urinary
excretion
data
showed
that
the
14C
portion
was
excreted
in
the
urine
from
5%
at
1
hr.
to
50%
at
6
hours
with
less
than
1%
of
the
65Zn
portion
being
excreted
in
the
urine
over
6
hours.

Klaassan
concluded
that
based
on
the
results
from
these
experiments,
it
is
apparent
that
the
inorganic
(
zinc)
and
organic
(
pyrithione)
portion
of
zinc
pyrithione
separate.
He
points
to
two
facts
that
strongly
demonstrate
this
point
and
they
are
the
differences
in
zinc
and
pyrithione
distribution
in
the
major
organs
and
the
differences
in
their
excretion
profiles.

EPA
Response:
The
text
was
revised
to
partially
adopt
some
of
the
suggested
changes.
The
language
now
states:
"
There
were
apparent
sex
differences
in
pharmacokinetics.
Klaasan
(
1976)
utilized
14C­
zinc
pyrithione
and
isotopic65­
zinc
pyrithione
to
study
zinc
omadine.
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
omadine
vs.
sodium
omadine
and
greater
retention
of
zinc
in
tissues
vs.
the
pyrithione
moiety.
"

Registrant
Comment:

EE.
Section
3.2
FQPA
Considerations,
page
17,
last
sentence
to
page
18,
1st
sentence
" 
the
developmental
toxicity
database
for
zinc
OMADINE

shows
effects
in
offspring
at
similar
dose
levels
as
effects
in
adults,
 ..".
25
Should
say:
"
No
developmental
effects
were
observed
at
concentrations
below
1.5
mg/
kg/
day
and
severe
maternal
toxicity
was
observed
at
1.5
and
3.0
mg/
kg/
day
for
zinc
OMADINE

,
 ."

See
comments
under
section
AA
EPA
Response:
No
change
was
made.
The
NOAELs
for
developmental
and
maternal
toxicity
are
identical.
See
response
under
section
AA.

Registrant
Comment:

FF.
Section
3.3
Dose­
Response
Assessment
Table
3
Toxicological
end­
points
top
of
page
19
row
Incidental
oral 
under
column
referring
to
toxicological
effects"

Correction:
Study
reference
should
be
for
"
Rats"
and
not
Rabbits
EPA
Response:
This
suggested
change
was
made.

Registrant
Comment:

GG.
Dietary
Exposure
and
Risk
4.2,
pg.
21,
Table
4.

Correction:
Table
4,
3rd
column
value
should
be
2.1
instead
of
1.3
Comment:
Footnote
b
does
not
include
the
aPAD
values
for
females
listed
in
Table
3,
0.0016
mg/
kg/
day,
and
this
value
was
not
used
in
the
calculation,
where
the
%
aPAD
for
females
would
be
2.1
if
the
lower
aPAD
is
used.

This
error
has
a
ripple
effect
into
the
DWLOC
calculation
for
females
and
the
aggregate
risk
calculations.
The
respective
corrections
would
be
in
Section
5.1,
Table
8
where
the
aPAD
for
females
would
be
0.00016,
the
Max
Acute
Water
Exposure
for
Females
would
be
0.000157
mg/
kg/
day
and
the
resulting
DWLOC
would
be
47
µ
g/
l
EPA
Response:
This
suggested
change
was
made.

Registrant
Comment:
HH.
Section
4.3
Drinking
Water
Exposure
and
Risk,
page
22,
1st
paragraph
"
Therefore,
the
Agency
is
presently
relying
on
computer
models
(
PECs)
of
pesticides
in
surface
water
to
estimate
drinking
water
exposure
to
zinc
OMADINE

"

This
statement
should
be
stricken.

Comment:
Does
the
Agency
mean
that
an
individual
may
drink
untreated
surface
water
from
a
freshwater
marina
as
opposed
to
the
untreated
water
from
a
freshwater
marina
26
being
an
individual's
main
source
of
drinking
water?
In
our
experience
all
surface
waters
are
treated
prior
to
being
used
for
drinking
water.

EPA
Response:
It
is
current
policy
to
use
computer
models
as
a
screening
tool
to
estimate
potential
concentrations
of
pesticides
in
surface
water
that
could
be
used
for
drinking
water.
The
Agency
has
refined
the
PECs
for
zinc
pyrithione
using
the
MAM­
PEC
model,
and
a
number
of
conservative
assumptions.
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
primary
use
of
this
model
by
the
Agency
at
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.
Based
on
the
refined
modeling,
there
are
no
oral
aggregate
risks
of
concern
for
food
and
water
exposures
to
zinc
pyrithione.

Registrant
Comment:

II.
Section
4.3
Drinking
Water
Exposure
and
Risk,
page
22,
2nd
paragraph,
" ..
(
PEC)
is
21.66
ppb
zinc
OMADINE

based
on
Luttik­
Johnson
Model."

Should
read
" 
acute
PEC
of
0.12
ppb "

Comment:
The
Agency
calculated
PEC
value
is
erroneous.
See
discussion
under
"
H"
above.
Refined
modeling
with
appropriate
parameters
is
suggested
to
obtain
realistic
PECs
EPA
Response:
The
Agency
has
revised
the
Environmental
modeling
chapter,
and
estimated
new
predicted
environmental
concentrations
(
PECs).

Registrant
Comment:

JJ.
Section
4.3
Drinking
Water
Exposure
and
Risk,
page
22,
2nd
paragraph,
5th
sentence,
"
The
primary
use
of
this
model
by
the
agency
at
this
stage
is
to
provide
a
course
screen "

Should
read,
"
The
primary
use
of
this
model
by
the
agency
at
this
stage
is
to
provide
a
coarse
screen "

EPA
Response:
The
text
was
modified
as
suggested.

Registrant
Comment:

KK.
Section
4.3
Drinking
Water
Exposure
and
Risk,
page
22,
3rd
paragraph,
last
sentence,
"
A
DWLOC
may
vary
with
drinking
water
consumption
patterns
ane
body
weight "
27
Should
read,
"
A
DWLOC
may
vary
with
drinking
water
consumption
patterns
and
body
weight "

EPA
Response:
The
suggested
change
was
made.

Registrant
Comment:

LL.
Section
4.4.2,
Dandruff
Shampoo
Exposure,
page
25
and
top
of
page
26,
all
references
to
"
Dandruff"
shampoo
should
be
"
Anti­
Dandruff"
shampoo.

Typographical
error
in
last
line
of
2nd
paragraph
referring
to
"
zine
OMADINE

"
,
should
be
"
zinc
OMADINE

"
.

EPA
Response:
This
suggested
change
was
made.

Registrant
Comment:

MM.
Section
4.4.2,
Dandruff
Shampoo
Exposure,
page
25,
2nd
paragraph
last
sentence " .
rather
than
from
soluble
zinc
OMADINE

complexed
with
detergent
in
the
commercial
shampoo"

This
part
should
be
stricken
because
the
zinc
OMADINE

does
not
complex
with
detergent
in
the
shampoo.

EPA
Response:
This
change
was
made.

Registrant
Comment:

NN.
Section
5.1.1.
Acute
Aggregate
Risk
Assessment
page
29,
3rd
sentence
"
Drinking
water...
could
occur
from
the
antifoulant
paint
use"

This
statement
is
incorrect.
See
comments
under
section
H
and
HH.

EPA
Response:
See
response
under
Section
HH.

Registrant
Comment:

OO.
Section
5.1.2
Acute
DWLOC
Calculations,
page
30,
2nd
full
paragraph
"
Using
a
conservative
screening­
level
model,
the
acute
(
maximum)
PEC
for
zinc
OMADINE

in
sea
water
is
21.66
ppb"

Should
read:
".. 
acute
PEC
of
0.12ppb.
28
Also
Table
8
on
page
30,
Table
9
on
page
33
and
Table
11
on
page
36
contain
erroneous
PEC
and
should
be
replaced
with
0.12
ppb
Comment:
See
discussion
on
PEC
under
H
above
EPA
Response:
The
Agency
has
revised
the
Environmental
modeling
chapter
and
estimated
new
predicted
environmental
concentrations
(
PECs).

Registrant
Comment:

PP.
Section
5.2
Short­
and
Intermediate­
Term
Aggregate
Risk,
Oral
Aggregate
Risk
Results,
full
paragraph
2
"
However,
the
DWLOC
for
infants/
children
of
17
µ
g/
L
is
slightly
less
than
the
PEC
of
21.66
µ
g/
L"

This
statement
is
incorrect
when
one
considers
a
PEC
of
0.12
ppb.
In
addition
to
the
fact
that
surface
water
are
routinely
treated
prior
to
use
as
drinking
water.

Comments:
See
H
and
HH
sections.

EPA
Response:
The
Agency
has
revised
the
Environmental
modeling
chapter
and
estimated
new
predicted
environmental
concentrations
(
PECs).
All
oral
aggregate
risks
are
below
the
Agency's
level
of
concern.

Registrant
Comment:

QQ.
Section
5.3.2,
Chronic
(
non­
Cancer)
DWLOC
Calculations,
page
35,
last
paragraph,
"
PEC
for
Zinc
OMADINE

in
sea
water
is
21.66
ppb"

Should
read
" 
acute
PEC
of
0.12
ppb "

Comment:
The
erroneous
PEC
value
should
be
replaced.
See
discussion
on
PEC
under
"
H"
above
and
DWLOC
discussion
under
"
HH"
above
.

EPA
Response:
The
Agency
has
revised
the
Environmental
modeling
chapter
and
estimated
new
predicted
environmental
concentrations
(
PECs).
All
oral
aggregate
risks
are
below
the
Agency's
level
of
concern.

Registrant
Comment:

RR.
Section
9,
Environmental
Risk,
Environmental
Fate,
page
41,
1st
paragraph,
6th
sentence,
"
Photolytic
measurements
showed
that
zinc
OMADINE

dissociates
in
13
minutes "
29
Should
read
"
Photolytic
measurements
showed
that
zinc
OMADINE

degrades
in
13
minutes "

EPA
Response:
The
suggested
change
has
been
incorporated.

Registrant
Comment:

SS.
Section
9,
Environmental
Risk,
Ecological
Hazard
and
Risk,
page
42,
1st
paragraph,
"
Zinc
OMADINE

is
very
highly
toxic
on
an
acute
basis
to
freshwater
and
marine
fish
and
invertebrates,
as
well
as
to
aquatic
plant
species".

Comment:
Request
that
a
sentence
following
the
above
sentence
describing
the
conditions
and
measures
taken
to
meet
guidelines
in
maintaining
test
substance
concentrations
throughout
the
aquatic
toxicity
tests.
The
results
are
highly
conservative
based
on
the
fact
that
under
normal
lighting
in
a
laboratory
greatly
diminishes
the
concentration
of
zinc
OMADINE

(
through
photolysis)
and
consequently
would
reduce
the
"
real­
life"
toxicity
to
fish
and
aquatic
plants.

Even
though
Zinc
OMADINE

LC50
values
for
fish
and
aquatic
plants
are
less
than
1.0
mg/
L
and
in
many
cases
goes
down
to
single
digits
of
the
µ
g/
L;
we
want
to
point
out
that
these
values
are
highly
conservative
as
in
all
of
the
fish
and
most
of
the
aquatic
plant
studies
light
intensity
was
reduced
by
75%
and
the
use
of
filters
to
block
the
350­
355
nm
wavelength
(
sensitive
wavelength
of
zinc
OMADINE

)
were
utilized
and
the
diluters
were
run
at
maximal
capacity
in
an
attempt
to
maintain
test
article
concentration
throughout
the
test
period.
Without
these
measures
pyrithione
levels
drop
dramatically
and
constant
levels
of
zinc
OMADINE

cannot
be
maintained
over
6
hours
let
alone
the
usual
96­
120
hours
for
acute
toxicity
tests.

EPA
Response:
The
ecological
hazard
section
of
the
document
provides
the
data
and
endpoints
used
in
the
risk
assessment.
When
an
acute
study
is
reviewed,
the
LC50
or
EC50
endpoint
is
used
to
determine
a
toxicity,
or
"
hazard"
classification
for
the
chemical,
as
outlined
in
OPP
Standard
Evaluation
Procedures.
Circumstances
which
may
affect
chemical
behavior
and,
thereby,
exposure
and
resulting
risk
in
the
natural
environment,
will
be
discussed
in
the
risk
assessment/
risk
characterization.
Since
the
antifouling
use
is
being
removed
from
the
risk
assessment
in
this
RED,
a
discussion
of
photolytic
breakdown
of
zinc
pyrithione
as
it
pertains
to
risk
will
not
be
included
in
this
document,
but
will
instead
be
included
in
the
reassessment
of
the
conditionally
registered
antifouling
products
after
submission
of
the
requested
ecotoxicity
studies.

Registrant
Comment:

TT.
In
section
9.0
Environmental
Risk
subsection
Ecological
Hazard
and
Risk,
page
42,
a
statement
indicating
that
"..
zinc
OMADINE

causes
adverse
impacts
on
freshwater
and
marine
invertebrate
reproduction
and
growth
at
very
low
levels.
Thus,
these
30
reproductive
impacts
indicate
that
zinc
OMADINE

is
a
potential
endocrine
disruptor."

Should
read:
"
Zinc
OMADINE

at
near
lethal
concentrations
i.
e.
at
or
near
the
LC50
values
reported
for
fish
and
invertebrates
was
observed
to
produce
limited
effects
to
reproduction
and
minor
effects
to
growth.
However,
at
doses
at
or
near
the
NOEC
for
zinc
OMADINE

no
effects
to
reproduction
or
growth
was
observed
in
any
aquatic
species
tested,
fish
or
invertebrate
thus
diminishing
any
concern
for
the
potential
of
endocrine
disruption."

Comment:
Ecological
Toxicity:
The
results
from
testing
zinc
OMADINE

in
the
Early
Life
Stage
Study
of
the
fathead
minnow
resulted
in
a
NOEC
of
1.22
µ
g/
L
following
32­
days
of
exposure
with
a
LOEC
of
2.82
µ
g/
L.
The
sensitive
toxic
endpoints
were
survival
and
sublethal
effects
at
hatch
and
days
7,
14,
21,
and
28
post
hatch.
There
was
no
apparent
effect
on
reproduction
but
in
the
AD
Preliminary
Risk
Assessment
there
is
mention
of
developmental
effects
to
the
fish
i.
e.
bent
bodies.
This
effect
only
was
observed
at
concentrations
above
1.22
µ
g/
L
( 
2.82
µ
g/
L)
and
only
became
visible
on
days
5­
10
and
again
on
days
17­
32
post
hatching,
strongly
suggesting
that
repeated
exposures
to
near
lethal
concentrations
of
zinc
Omadine
®
was
responsible
for
this
effect
and
not
developmental
toxicity.
NOTE:
The
Acute
LC50
in
fathead
minnow
for
zinc
OMADINE

is
2.68
µ
g/
L
(
see
table
13
page
42
of
the
AD
Preliminary
Risk
Assessment).

The
results
from
testing
zinc
OMADINE

in
the
Chronic
Toxicity
to
the
Daphnid,
Daphnia
magna
with
Zinc
OMADINE

demonstrated
that
the
NOEC
is
2.7
µ
g/
L
and
the
LOEC
is
5.8
µ
g/
L.
Doses
tested
were
0,
2.7,
5.8,
12,
22,
and
49
µ
g/
L.
The
LC50
for
Daphnid
reported
in
the
AD
Preliminary
Risk
Assessment
is
8.25
µ
g/
L.
The
mean
day
to
the
first
brood
was
delayed
at
22
and
49
µ
g/
L,
concentrations
that
clearly
produce
significant
toxicity
to
the
Daphnid.
At
concentrations
of
12
and
22
µ
g/
L
lengths
were
affected
(
however,
differences
in
length
never
achieved
statistical
significance;
no
animals
survived
to
day
32
at
49
µ
g/
L),
again
concentrations
of
zinc
OMADINE

causing
an
effect
to
length
also
are
producing
significant
toxicity
i.
e.
LC50
8.25
µ
g/
L
(
significant
mortality
was
observed
at
49
µ
g/
L
starting
on
day
2
with
near
100%
mortality
by
day
6).
The
Chronic
Toxicity
of
Zinc
OMADINE

to
the
Mysid,
Americamysis
bahia
resulted
in
a
NOEC
of
2.28
µ
g/
L
and
a
LOEC
of
4.20
µ
g/
L.
The
LC50
for
Mysid
is
4.7
µ
g/
L
as
reported
in
the
AD
Preliminary
Risk
Assessment.
At
concentrations
of
zinc
OMADINE

that
allowed
survival
equal
or
similar
to
control
values,
no
reproductive
effects
were
observed.

Conclusion:
Zinc
OMADINE

appears
to
be
more
of
an
acute
hazard
over
a
chronic
hazard,
based
on
review
of
the
acute
LC50/
NOEC
and
chronic
LOEC/
NOEC
values.
The
chronic
NOEC
values
are
in
every
case
similar
to
the
acute
NOEC
values.
The
fact
that
only
doses
of
zinc
Omadine
®
that
were
near
or
greater
than
the
31
corresponding
LC50
were
resulting
in
effects
in
reproduction
etc.
strongly
argues
against
any
chronic
hazard
and
definitely
confounds
any
interpretation
of
possible
endocrine
disruption.

EPA
Response:
This
comment
is
beyond
what
is
considered
"
error
correction."

Registrant
Comment:

UU.
Section
9.0,
page
42,
Table
13,

Corrections
to
Table.
Waterflea
LC50
should
be
34
ppb
and
95%
confidence
intervals
should
read
28
 
41
(
MRID
44921801).
NOAEC
should
be
13
ppb.

EPA
Response:
The
MRID
number
(
44921801)
and
values
reported
refer
to
an
acute
study
with
Hyalella
azteca,
not
the
waterflea
(
Daphnia
magna).
The
Hyalella
study
was
originally
submitted
toward
fulfillment
of
acute
sediment
toxicity
data
requirements,
as
Hyalella
is
a
sediment­
dwelling/
utilizing
organism.
However,
the
study
was
actually
conducted
as
a
water
column
toxicity
study,
and
was
therefore
inappropriate
to
use
to
evaluate
sediment
toxicity.
It
was
reviewed
and
classified
as
supplemental
information,
but
was
not
included
in
the
RED
as
it
does
not
meet
the
requirements
for
either
an
acute
freshwater
invertebrate
study
or
a
freshwater
sediment
toxicity
study.
It
will
be
added
to
the
ecological
hazard
chapter
and
preliminary
risk
assessment
as
additional
information,
indicating
that
zinc
pyrithione
is
highly
toxic
to
freshwater
invertebrates.

Registrant
Comment:

VV.
Section
9.0,
page
43,
Table
13,

Corrections
to
Table.
Algae
and
aquatic
plants.
Freshwater
algae
NOAEC
should
be
7.8
ppb
(
MRID#
43864609);
Anabaena
NOAEC
should
be
3.8
ppb
(
MRID#
45564901);
Navicula
NOAEC
should
be
2.4
ppb
(
MRID#
45565001);
Lemna
gibba
NOAEC
should
be
4.0
ppb
(
MRID#
45204104).

EPA
Response:
This
table
was
revised
to
include
these
comments.

Registrant
Comment:

WW.
Section
9.0,
page
43,
Table
14,
Freshwater
fish
early
life
stage
toxicity
data
Correction
to
Table.
Fathead
minnow
EC50
should
be
1.9
ppb
(
MRID#
44591204);
NOAEC
should
be
1.22
ppb
and
the
LOAEC
is
2.82
ppb
(
Table
indicated
282
ppb
for
NOAEC)
32
EPA
Response:
We
have
no
record
of
any
zinc
omadine
study
with
an
MRID
#
of
44591204.
The
acute
fathead
minnow
study
we
have
is
MRID
#
438646­
06,
which
provided
and
LC50
of
2.68
ug
ai/
L
and
a
NOEC
of
1.1
ug
ai/
L.
The
chronic,
MRID
#
452041­
02,
provided
a
NOEC
of
1.22
ppb,
and
a
LOEC
of
2.82
ppb.
This
latter
study
appears
to
be
the
study
referred
to
in
the
registrants'
comments.
The
incorrect
value
of
282
ppb
appears
to
be
a
typographical
error
in
the
summary
tables
which
was
corrected.

Registrant
Comment:

XX.
Section
9.0,
page
44,
Table
14
Freshwater
Invertebrate
Life
Cycle
Toxicity
Data
Correction
to
Table
Waterflea
EC50
should
be
29
ppb
(
MRID#
44535401);
and
NOAEC
should
be
2.7
ppb
and
the
LOAEC
should
be
5.8
ppb.;
Mysid
EC50
should
be
5.2
ppb
and
NOAEC
should
be
2.3
ppb;
LOAEC
should
be
4.2
ppb.

EPA
Response
While
the
EC50
values
listed
in
the
registrant
comment
are
correct
(
except
the
Mysid
EC50
is
4.7
ppb),
they
are
from
chronic
testing,
and
were
therefore
not
included
in
the
table
14.
Fish
early
life­
stage
and
aquatic
invertebrate
life­
cycle
studies
provide
two
endpoints
used
to
calculate
chronic
risk
quotients:
the
NOAEC
and
the
LOAEC.
While
the
LC50/
EC50
values
from
chronic
studies
may
be
considered
when
assessing
the
study
for
scientific
validity
and
in
the
risk
characterization,
they
are
not
included
in
the
tables
in
order
to
avoid
any
confusion
with
the
acute
values.
The
LC50
or
EC50
from
acute
studies
are
used
to
calculate
risk
quotients
in
the
assessment
of
acute
risk,
and
are
listed
in
a
separate
table.
Table
14
will
be
modified
to
list
only
acute
values,
with
the
chronic
endpoints
placed
in
a
new
table
15
that
does
not
have
a
LC50
column.

Registrant
Comment:

YY.
Section
9.0,
page
46,
1st
paragraph
"
Environmental  .
invertebrates.
The
antifoulant
use
of
zinc
OMADINE

is
likely
to
result
in
adverse
effects
to
fish,
aquatic
plants
and
aquatic
invertebrates,
including
endangered
species.

This
paragraph
should
be
stricken
because
this
is
an
incorrect
conclusion
based
on
an
incorrect
PEC
calculation
(
see
section
H).

Comment:
As
discussed
previously
in
section
H,
the
exposure
modeling
was
a
preliminary
risk
assessment
that
needs
further
refinement,
particularly
since
it
is
tenfold
higher
than
measured
concentrations
of
widely­
used
antifouling
biocide,
e.
g.
Irgarol,
that
is
persistent.
If
the
modeling
is
refined
using
the
proper
parameters
for
leach
rate
and
degradation
(
see
section
H,
Table
3
and
4),
the
PEC
will
be
a
factor
of
33
10
to
a
1000
less
than
the
NOEC
of
the
most
sensitive
aquatic
organisms.
These
refined
PECs
will
not
exceed
the
LOCs.

EPA
Response:
The
antifouling
use
of
zinc
Omadine
is
being
removed
from
the
risk
assessment
in
this
RED
for
assessing
ecological
risks,
and
will
be
considered
during
the
reassessment
of
the
conditionally
registered
antifouling
products.

Registrant
Comment:

ZZ.
Section
10.0,
page
46
Data
Deficiencies
/
Data
Needs:

Comment:
We
have
generated
data
on
aquatic
plants
and
whole
sediment
toxicity
study
to
support
our
antifoulant
use
of
zinc
OMADINE

.

EPA
Response:
The
ecological
hazard
chapter
and
preliminary
risk
assessment
will
be
updated
to
include
any
data
which
have
been
submitted
and
accepted
since
the
chapter
was
originally
drafted.
This
will
not
include
studies
that
are
still
in
progress,
however.
Data
from
any
in­
process
studies
will
be
reviewed
and
utilized
in
the
revised
risk
assessment
for
the
conditionally
registered
antifouling
products.