Page
1
of
33
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
DC
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
July
11,
2005
MEMORANDUM:

Subject:
Occupational
and
Residential
Exposure
Chapter
for
Azadioxabicyclooctane
To:
Tom
Luminello,
Chemical
Review
Manager
Antimicrobials
Division
From:
Talia
Milano,
Chemist
Risk
Assessment
and
Science
Support
Branch
(
RASSB)
Antimicrobials
Division
(
7510C)

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

Case
No.:
3023
Chemical
Name:
PC
Codes:
CAS
Registry
No.

(
5­
Hydroxymethoxymethyl­
1­
aza­
3,
107001
59720­
42­
2
7
dioxabicyclo(
3.3.0)
octane
(
5­
Hydroxymethyl­
1­
aza­
3,
107002
6542­
37­
6
7­
dioxabicyclo(
3.3.0)
octane
(
5­
Hydroxypoly(
methylene­
oxy)*
methyl­
1­
aza­
3,
7­
dioxabicyclo(
3.3.0)
octane
107003
56709­
13­
8
*(
74%
C
2
,
21%
C
3
,
4%
C
4
,
1%
C
5
)
Page
2
of
33
Azadioxabicyclooctane
Occupational/
Residential
Exposure
Assessment
CASE
3023
PC
CODES
107001,
107002,
107003
July
7,
2005
Office
of
Pesticide
Programs
Antimicrobials
Division
U.
S.
Environmental
Protection
Agency
1200
Pennsylvania
Avenue,
NW
Washington,
DC
20460
Page
3
of
33
TABLE
OF
CONTENTS
Title
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Executive
Summary
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1.0
INTRODUCTION
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1.1
Purpose
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1.2
Criteria
for
Conducting
Exposure
Assessments
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1.3
Chemical
Identification
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1.4
Physical/
Chemical
Properties
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2.0
USE
INFORMATION
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2.1
Formulation
Types
and
Percent
Active
Ingredient
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2.2
Summary
of
Use
Pattern
and
Formulations
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3.0
SUMMARY
OF
TOXICITY
CONCERNS
RELATING
TO
EXPOSURE
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3.1
Acute
Toxicity
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3.2
Summary
of
Toxicity
Concerns
Relating
to
Exposure
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3.3
FQPA
Considerations
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4.0
RESIDENTIAL
EXPOSURE
ASSESSMENT
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4.1
Summary
of
Registered
Uses
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4.2
Dietary
Exposure/
Risk
Pathway
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4.3
Drinking
Water
Exposure/
Risk
Pathway
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4.4
Residential
Exposure/
Risk
Pathway
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4.4.1
Residential
Handler
Exposure
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4.4.1.1
Painter
Exposure
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4.4.2
Postapplication
Exposure
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4.5
Data
Uncertainty
and
Limitations
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5.0
RESIDENTIAL
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
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6.0
OCCUPATIONAL
EXPOSURE
AND
RISK
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6.1
Occupational
Handlers
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6.1.1
Occupational
Worker
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6.1.1.1
Occupational
Handler
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6.2
Occupational
Post
application
Exposure
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6.2.1
Occupational
Worker
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6.2.2
Metal
Working
Fluid
Machinist
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6.3
Data
Uncertainty
and
Limitations
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7.0
REFERENCES
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Page
4
of
33
EXECUTIVE
SUMMARY:

This
document
contains
the
Occupational
and
Residential
Exposure
Chapter
of
the
Azadioxabicyclooctane
Reregistration
Eligibility
Decision
Document
(
RED).
This
addresses
the
potential
exposures
and
risks
to
humans
that
may
occur
when
a
person
is
exposed
to
azadioxabicyclooctane
in
"
occupational
settings"
or
in
"
residential
settings."
This
RED
Chapter
estimates
exposures
and
risks
to:
(
1)
handlers
(
mixers,
loaders,
applicators)
of
azadioxabicyclooctane
products;
and
(
2)
individuals
who
are
involved
in
post
application
activities
or
occupy
areas
where
azadioxabicyclooctane­
containing
products
have
been
recently
applied.

Azadioxabicyclooctane,
a
microbiocide/
microbiostat
that
controls
slime
forming
bacteria
and
fungi,
is
registered
for
use
as
a
materials
preservative
per
label
number
1529­
28,
in
latex
paints,
latex
emulsions,
pigment
dispersions,
inks,
adhesives,
construction
materials,
metalworking
fluids,
textile
fiber
finish
(
only
for
use
on
fibers
that
don't
come
into
direct
contact
with
skin),
pulp
and
paper
(
treated
paper
and
paper
board),
general
use
in
petroleum
production
and
recovery,
and
wax
emulsions.
The
use
of
azadioxabicyclooctane
in
"
pulp
and
paper"
mill
suggests
that
it
is
used
as
a
slimicide.
This
is
not
consistent
with
the
use
level
summary
table,
which
only
addresses
the
use
rates
for
paper
coatings.
If
the
registrant
decides
to
support
the
slimicide
use,
this
information
needs
to
be
provided.
The
use
sites
are
listed
on
label
#
1529­
28
to
be,
"...
pulp
and
paper
(
treated
paper
and
paper
and
paper
board
intended
for
producing
manufacturing,
packaging,
processing,
treating
or
preparing
food
products
must
be
limited
to
contact
with
dry
food)..."
Also,
on
the
label
it
states,
"
the
maximum
level
permitted
for
all
other
applications
listed
[
other
than
metal
working
fluids]
is
0.5%."
The
application
rate
on
the
label
is
in
reference
to
the
amount
of
product
to
use
by
weight
of
the
material
to
be
treated.
The
active
ingredient
(
a.
i.)
comprises
50%
of
the
product
formulation.
The
label
also
includes
a
use
specific
recommended
maximum
and
minimum
use
level
for
each
specific
use
site.
In
certain
parts
of
this
assessment,
the
minimum
use
level
was
also
assessed.
This
is
because
in
some
cases,
the
maximum
application
of
0.5%
(
0.25%
a.
i.)
by
weight
of
the
material
treated
generates
an
MOE
of
concern.
However,
when
the
recommended
minimum
level
is
assessed,
the
MOE
does
not
exceed
the
Agency's
level
of
concern.

The
residential
setting
exposure
scenarios
that
were
identified
result
from
a
painter
applying
paint
that
has
been
preserved
with
azadioxabicyclooctane
through
either
airless
spraying
or
brush/
roller
painting.
Both
of
these
applications
are
performed
ungloved.
The
residential
dermal
and
inhalation
exposures
assessed
in
this
document
represent
short
term
(<
30
days)
durations.
There
is
no
intermediate
(
1­
3
months)
or
long
term
(>
3
month)
exposure
risks
to
assess
because
of
the
frequency
that
a
residential
painter
is
assumed
to
come
into
contact
with
azadioxabicyclooctane
treated
paint.
In
addition,
postapplication
residential
dermal
exposures
are
not
assessed
for
contact
with
wet
paint
because
the
paint
is
expected
to
dry
within
a
day,
so
any
potential
exposure
is
expected
to
be
negligible.
The
potential
postapplication
inhalation
exposure
is
also
expected
to
be
minimal
because
azadioxabicyclooctane
has
a
low
vapor
pressure
(
i.
e.
<
2.1x10­
5
mmHg
@
20oC)
and
is,
therefore
not
likely
to
generate
sufficient
vapor
to
cause
an
inhalation
concern
to
the
residential
populations
performing
post
application
tasks,
or
occupying
Page
5
of
33
treated
areas.
Thus,
there
are
no
risk
concerns
and
inhalation
postapplication
exposures
were
also
not
quantitatively
evaluated.

If
a
residential
painter
is
handling
paint
treated
at
the
maximum
permissible
level
of
0.5%
product
by
weight
of
material
being
treated,
the
dermal
MOE
for
the
brush/
roller
application
is
greater
than
the
target
short
term
MOE
of
300.
However,
the
dermal
MOE
for
the
individual
that
applies
the
paint
through
airless
spraying,
is
236,
which
is
less
than
the
target
MOE
of
300.
There
is
also
concern
with
the
risks
associated
with
inhalation
exposure
for
the
airless
spay
application.
The
target
inhalation
MOE
is
3,000,
and
for
the
brush/
roller
application,
the
MOE
is
53,000
which
is
not
a
concern,
but
for
the
airless
sprayer
application,
the
inhalation
MOE
is
2,400,
and
this
is
less
than
3,000.
Because
of
the
issues
with
the
scenario
of
a
residential
painter
applying
paint
(
treated
at
0.5%
product
by
weight
of
the
material
treated)
via
airless
spraying,
the
minimum
rate
of
0.1%
(
0.05%
a.
i.)
product
by
weight
of
the
paint
treated
(
as
stated
on
label
1529­
28)
was
assessed
as
well.
As
a
result,
the
inhalation
MOE
calculated
for
exposure
to
paint
treated
at
this
minimum
rate
is
12,000
which
is
well
above
the
target
inhalation
MOE
of
3,000.
This
is
further
discussed
in
Section
4.4.1.1,
Painter
Exposure.

There
are
several
occupational
uses
of
azadioxabicyclooctane
that
have
been
identified
(
both
handler
and
postapplication).
The
occupational
risks
result
from
the
following
scenarios:
the
worker
introducing
azadioxabicyclooctane
as
a
materials
preservative
into
the
label
specified
materials
through
liquid
pour
or
pump
(
manufacturing),
a
professional
painter
applying
"
already
preserved
paint"
via
brush/
roller
or
airless
spraying,
or
a
machinist
who
may
handle
"
already
preserved"
metal
working
fluids
(
MWF).
The
application
rate
of
0.5%
(
0.25%
a.
i.)
product
by
weight
of
material
being
treated
was
used
for
assessing
all
of
the
liquid
pour
and
liquid
pump
applications
of
the
chemical
as
a
materials
preservative
and
for
the
professional
painter
scenarios.
However,
there
was
one
exception
as
specified
on
the
label.
The
maximum
rate
allowed
for
MWFs
is
0.3%
(
0.15%
a.
i.)
product
by
weight
of
MWF
treated.

The
scenarios
for
the
preservation
of
paints,
brush/
roller
painting,
metalworking
fluids,
and
paper
coatings
were
all
acceptable
for
short
term
and
intermediate
term
exposures
because
the
dermal
and
inhalation
MOEs
were
above
the
target
MOEs.
However,
when
a
professional
painter
applies
paint
that
has
already
been
treated
at
an
application
rate
of
0.5%
(
0.25%
a.
i.)
product
by
weight
of
paint
treated
via
airless
spraying,
the
inhalation
MOE
is
720,
which
is
less
than
the
target
inhalation
MOE
of
3,000.
If
painter
is
handling
paint
that
has
been
pre­
treated
at
the
minimum
application
rate
of
0.1%
(
0.05%
a.
i.)
product
by
weight
of
the
paint
treated,
the
inhalation
MOE
is
3,600,
which
is
not
of
concern.

Post
application
handler
exposure
to
pre­
treated
MWF
was
also
assessed,
but
only
for
long­
term
(
LT)
exposure.
There
are
no
inhalation
risks
because
the
inhalation
MOE
is
well
above
the
target
MOE
of
3,000.
Dermal
risks
were
also
assessed
assuming
that
the
worker
fully
immerses
both
hands
into
the
already
treated
fluid,
and
the
MOEs
were
compared
to
the
target
LT
MOE
of
1,000.
If
the
worker
handles
MWF
that
has
been
treated
at
an
application
rate
of
0.3%
(
0.15%
a.
i.)
product
by
weight
of
MWF
treated,
the
dermal
MOE
is
540,
which
is
less
than
Page
6
of
33
the
target
dermal
MOE
of
1,000.
However,
if
the
machinist
is
handling
MWF
that
has
been
pretreated
at
the
minimum
application
rate
of
0.1%
(
0.05%
a.
i.)
product
by
weight
of
the
fluid
treated,
the
dermal
MOE
is
1,600,
which
is
not
of
concern.

All
of
the
occupational
scenarios
are
further
discussed
in
Section
6.0,
Occupational
Exposure.

The
following
list
provides
a
summary
of
the
limited
or
lacking
data
that
were
used
in
this
assessment.
Each
of
these
scenarios
is
addressed
in
more
detail
in
the
body
of
this
document.

°
Unit
exposure
data
for
each
of
the
worker
scenarios
assessed,
°
Chemical
metering
exposure
data
for
secondary
recovery
operations
in
oil­
fields.

The
scenarios
represented
in
the
risk
assessment
are
provided
in
Table
E1.
These
scenarios
have
been
selected
based
on
examination
of
the
product
label
(
Reg
#
1529­
28,
Nuosept
95
Preservatives),
which
indicates
the
use
sites
for
this
chemical
as
a
preservative.
Page
7
of
33
Table
E1:
Summary
of
Handler
Exposure
Scenarios
and
Risks
for
Azadioxabicyclooctane
AD
Use
Category
Exposure
Scenario
Occupational
Exposures
Material
Preservatives
Worker
pouring
or
pumping
azadioxabicyclooctane
as
a
preservative
into
adhesives
(
natural­
based
or
synthetic),
caulks,
latex
emulsions,
wax
emulsions,
latex
paint,
inks,
pigment
dispersion,
pigment
slurry,
sealants,
and
textile
fiber
finishes.

Worker
pouring
or
pumping
azadioxabicyclooctane
as
a
preservative
into
paper
coatings.
a
Worker
pouring
or
pumping
azadioxabicyclooctane
as
a
preservative
into
metalworking
fluids.

Machinist
handling
already
treated
metalworking
fluid
Professional
end­
use
of
already
azadioxabicyclooctane
treated
drilling
muds
and
flooding
fluids
for
gas/
oil
recovery
systems.

Professional
application
of
paint
treated
with
azadioxabicyclooctane
using
an
airless
spraying
application
method.

Professional
application
of
paint
treated
with
azadioxabicyclooctane
using
a
paint
brush.

Residential
Exposures
Material
Preservatives
Applying
paint
treated
with
azadioxabicyclooctane
using
an
airless
spraying
application
method.

Applying
paint
treated
with
azadioxabicyclooctane
using
a
paint
brush.

a:
The
discrepancy
on
label
1529­
28
needs
to
be
clarified
as
to
whether
or
not
azadioxabicyclooctane
is
used
for
pulp
and
paper
or
for
paper
coatings
because
both
of
these
uses
are
on
the
label,
but
a
rate
is
only
provided
for
the
paper
coating
use.
Page
8
of
33
1.0
INTRODUCTION
1.1
Purpose
This
document
contains
the
Occupational
and
Residential
Exposure
Chapter
of
the
Azadioxabicyclooctane
Re­
registration
Eligibility
Decision
Document
(
RED)
and
addresses
potential
exposures
and
risks
to
humans
who
may
be
exposed
to
azadioxabicyclooctane
in
"
occupational
settings"
or
in
"
residential
settings."

1.2
Criteria
for
Conducting
Exposure
Assessments
In
this
specific
chapter,
handler
exposures
are
calculated
and
presented
to
assess
dermal
and
inhalation
risks
associated
with
antimicrobial
uses
of
azadioxabicyclooctane.
Handlers
are
defined
by
the
U.
S.
Environmental
Protection
Agency
(
EPA)
as
those
individuals
who
are
exposed
to
the
formulated
product
(
e.
g.,
adding
azadioxabicyclooctane
as
a
preservative)
along
with
those
individuals
that
are
exposed
to
the
active
ingredient
as
a
direct
result
of
its
incorporation
into
an
end
use
product
(
e.
g.,
individuals
using
the
paint
that
in
itself
is
not
a
registered
product).
Handler
exposure
occurs
in
both
the
occupational
and
residential
settings.

Inhalation
and
dermal
risks
to
handlers
are
determined
by
calculating
the
Margin
of
Exposure
(
MOE)
for
each
scenario
considered.
An
MOE
represents
how
close
the
risk
associated
with
a
chemical
exposure
is
to
being
a
concern.
Specifically,
an
MOE
is
a
ratio
of
the
toxicological
endpoint
of
concern
(
i.
e.,
NOAEL
or
LOAEL)
to
the
body
burden
(
i.
e.,
daily
dose).
Daily
dose
values
are
determined
by
combining
scenario
specific
unit
exposure
levels
and
use
rates,
which
are
then
normalized
by
body
weight.
The
equations
used
in
order
to
calculate
the
MOEs
are
presented
below,
and
are
referenced
to
throughout
the
document.

°
Daily
Exposure
Daily
exposure
is
the
amount
of
active
ingredient
(
i.
e.,
azadioxabicyclooctane)
an
individual
is
exposed
to
per
day
by
inhalation
or
dermal
routes
of
exposure.

°
Unit
Exposure
Unit
exposures
are
the
exposures
to
the
handler
(
mg
a.
i.)
normalized
by
the
amount
handled
(
lb
a.
i.)
for
the
chemical.
As
chemical
specific
unit
exposures
were
not
available
for
azadioaxabicyclooctane,
surrogate
unit
exposure
data
were
used
to
determine
daily
exposure.
The
surrogate
unit
exposure
data
used
are
from
the
Equation
1
­
Daily
Exposure
Daily
Exposure
(
mg
a.
i./
day)
=
Unit
Exposure
(
mg
a.
i./
lb
a.
i.)
x
Use
Rate
(
lb
a.
i./
day)
Page
9
of
33
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study
(
CMA,
1999),
as
reported
in
EPA's
Evaluation
of
the
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study
(
Amended
on
December
8,
1999)
(
U.
S.
EPA,
1999)
along
with
the
PHED
Handlers
Exposure
Database
(
PHED
V1.1),
as
reported
in
the
PHED
Surrogate
Exposure
Guide
(
PHED,
1997).

°
Use
Rate
Use
rates
are
the
amount
of
active
ingredient
(
i.
e.,
azadioxabicyclooctane)
handled,
which
are
determined
using
the
percent
of
the
active
ingredient
in
the
chemical,
application
rates,
and
the
amount
of
the
substrate
which
is
treated
with
the
chemical
daily
(
or
the
amount
of
treated
substrate
handled
daily).

°
Daily
Dose
Daily
dose
is
the
amount
active
ingredient
received
from
exposure
to
a
chemical
in
a
given
scenario
per
day,
normalized
by
the
weight
of
the
individual
who
is
exposed.

°
Daily
Exposure
Daily
exposure
is
the
amount
of
active
ingredient
(
i.
e.,
azadioaxabicyclootane)
an
individual
is
exposed
to
per
day
by
inhalation
or
dermal
routes
of
exposure
(
See
Equation
1).

°
Absorption
Factor
(
if
applicable)
The
absorption
factor
is
a
measure
of
the
flux
or
amount
of
chemical
that
crosses
a
biological
boundary
such
as
the
skin
(
i.
e.,
percentage
of
the
total
available
absorbed).
This
is
not
used
in
the
calculations
for
this
specific
chemical
because
the
study
that
was
used
to
derive
the
dermal
LOAEL
is
a
21­
day
dermal
study,
and
not
an
oral
study.
If
an
oral
study
was
used
to
derive
the
LOAEL,
then
this
chemical
specific
absorption
factor
would
be
incorporated
to
make
the
oral
LOAEL
representative
of
dermal
exposure.
In
addition,
for
inhalation,
it
was
assumed
that
absorption
was
100%
by
oral
absorption,
because
an
oral
study
was
used
to
assess
inhalation
exposures.

°
Body
Weight
The
body
weight
represents
the
population
of
interest
in
a
risk
assessment.
For
this
Equation
2
­
Daily
Dose
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Daily
Exposure
(
mg
a.
i./
day)
x
Absorption
Factor
(%)
Body
Weight
(
kg)
Page
10
of
33
risk
assessment,
the
population
of
interest
for
handlers
is
male
and
female
adults.
As
such,
a
body
weight
of
70
kg
is
used
in
all
calculations.

°
MOE
The
MOE
(
margin
of
exposure)
value
represents
risk
or
how
close
a
chemical
exposure
is
to
being
a
concern.

°
Toxicity
Endpoint
The
toxicity
endpoint
is
the
dose
level
used
in
a
toxicity
study.
It
can
either
be
the
no
observed
adverse
effects
level
(
NOAEL)
or
the
lowest
observed
adverse
effects
level
(
LOAEL).
As
shown
in
Table
3,
dermal
exposures
are
assessed
using
a
LOAEL
of
100
mg/
kg/
day
(
from
a
dermal
toxicity
study)
and
inhalation
exposures
are
assessed
using
a
NOAEL
of
10.6
mg/
kg/
day
(
from
an
oral
toxicity
study).

°
Daily
Dose
Daily
dose
is
the
amount
active
ingredient
(
i.
e.,
azadioxabicyclooctane)
received
from
exposure
to
a
chemical
in
a
given
scenario
per
day,
normalized
by
the
weight
of
the
individual
that
is
exposed.

1.3
Chemical
Identification
Product
Name:
hydroxypoly
(
methyleneoxy)
bicyclic
oxazolidine
Common
Name:
Nuosept
95,
Azadioxabicyclooctane
CAS
Number:
56709­
13­
8
Active
Ingredients:
(
a)
5­(
Hydroxymethoxy)
methyl­
1­
aza­
3,
7­
dioxabiyclo
[
3.3.0]
octane
(
b)
5­
Hydroxymethyl­
1­
aza­
3,
7­
dioxabicyclo
[
3.3.0]
octane
(
c)
5­(
Hydroxypoly[
methyleneoxy
(
74%
C
2
,
21%
C
3
,
4%
C
4
,
1%
C
5
)])
methyl­
1­
aza­
3,
7­
dioxabicyclo
[
3.3.0]
octane
1.4
Physical/
Chemical
Properties
Physical
and
chemical
properties
for
the
product
Nuosept
95
are
provided
in
MRID
#
416716­
03.
This
product
includes
three
active
ingredients,
which
need
to
be
at
equilibrium
in
the
appropriate
proportions
for
the
product
to
be
used
successfully.
This
is
why
the
Equation
3
­
Margin
of
Exposure
MOE
=
Toxicity
Endpoint
(
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)
Page
11
of
33
chemical
properties
below
are
not
chemical
specific,
they
are
product
specific:

Color:
Pale
Yellow
Physical
State:
Clear
liquid
Odor:
Mild
characteristic
odor
Stability
to
Sunlight,
Normal
and
Elevated
Temperatures,
Metals/
Metal
Ions:
Stable
pH
of
Water
Solutions
or
Suspensions:
@
25OC,
pH
=
6.33
Boiling
Point
(
BP)/
Boiling
Range:
@
760mm
Hg,
BP
=
104.7OC
Density/
Relative
Density/
Bulk
Density:
@
25OC,
the
specific
gravity
is
1.444g/
mL
(
9.55
lb/
gal)
a
Dissociation
Constant
in
Water:
4.5
0.5
±
Partition
Coefficient
(
n­
Octanol/
H
2
O):
<
10
Vapor
Pressure
(
VP):
@
20OC,
VP
=
<
2.1x10­
5
mm
Hg
a:
1.144g/
mL
x
(
1000mL/
1
Liter)
x
(
1
Liter/
0.26417
gal)
x
(
0.00220
lb/
g)
=
9.55
lb/
gal
2.0
USE
INFORMATION:

2.1
Formulation
Types
and
Percent
Active
Ingredient
Azadioxabicyclooctane
is
formulated
as
a
soluble
liquid
and
contains
approximately
50
percent
active
ingredient.
The
active
ingredient
is
an
equilibrium
mixture
of
the
following
three
azadioaxabicyclootanes:
5­
Hydroxymethl­
1­
aza­
3,
7­
dioxabicyclo
(
3.3.0)
octane
(
16.0%
of
the
product
formulation),
5­
Hydroxymethoxymethyl­
1­
aza­
3,
7­
dioxabicyclo
(
3.3.0)
octane
(
28.8%
of
the
product
formulation),
and
5­(
Hydroxypoly[
methyleneoxy
(
74%
C
2
,
21%
C
3
,
4%
C
4
,
1%
C
5
)])­
1­
aza­
3,
7­
dioxabicyclo
(
3.3.0)
octane
(
5.2%
of
the
product).
Removal
of
any
one
component
will
shift
the
equilibrium
to
replace
the
missing
component,
resulting
in
a
different
chemical
with
different
properties.
As
such,
it
is
impossible
to
separate
the
components
and
test
each
individually.
There
is
only
one
EPA
registered
product
with
the
active
ingredient
azadioxabicyclooctane
(
Nuosept
95
Preservative,
EPA
Registration
No.
1529­
28).

2.2
Summary
of
Use
Pattern
and
Formulations
The
Agency
has
determined
the
potential
exposures
of
azadioxabicyclooctane
to
occupational
and
residential
handlers
by
identifying
exposure
scenarios
based
on
plausible
application
methods
given
the
label
uses.
The
occupational
and
residential
use
patterns
of
azadioxabicyclooctane
identified
by
EPA
are
listed
in
Table
1
below.
The
application
rates
presented
in
Table
1
are
the
maximum
application
rates
for
each
use
that
is
listed
on
label
1529­
28.
Page
12
of
33
Table
1:
Exposure
Scenarios
and
Use
Patterns
for
Azadioxabicyclooctane
Uses
Method
of
application
Application
Rate
in
%
product
(%
a.
i.)
by
weight
of
material
treateda
Material
Preservatives
Adhesives
(
synthetic
and
naturalbased

Liquid
Pour
Liquid
Pump
0.5
(
0.25)
Caulks
Drilling
muds/
Flooding
fluids
Latex
emulsions
Wax
Emulsions
Inks
Paper
Coatingsb
Pigment
dispersions
Pigment
Slurry
Sealants
Textile
Fiber
Finish
Latex
Paint
Airless
Spray
Brush/
Roller
Liquid
Pour
Liquid
Pump
Metal
working
fluids
Liquid
Pour
Liquid
Pump
0.3
(
0.15)

a:
The
maximum
rate
is
what
is
presented,
because
label
1529­
28
states,
"
the
maximum
level
permitted
for
all
other
applications
listed
[
other
than
metal
working
fluids]
is
0.5%
[
product
by
weight
of
material
to
be
treated]."
The
application
rate
on
the
label
is
in
reference
to
the
amount
of
product
to
use
by
weight
of
the
material
to
be
treated.
It
is
important
to
note
that
50%
of
the
product
is
the
active
ingredient
(
a.
i.),
and
this
is
what
is
reflected
in
the
table
in
parenthesis
as
well
as
throughout
the
assessment.
b:
The
label
presents
pulp
and
paper
as
a
use.
However,
on
the
use
rate
table,
the
paper
coating
use
is
listed.
These
are
two
different
uses
and
this
needs
to
be
clarified
so
that
the
correct
use
scenario
can
be
identified.
Page
13
of
33
3.0
SUMMARY
OF
TOXICITY
CONCERNS
RELATING
TO
EXPOSURE
3.1
Acute
Toxicity
3.2
Summary
of
Toxicity
Concerns
Relating
to
Exposure
Toxicological
endpoints
and
associated
uncertainty
factors
used
in
assessing
the
risks
of
azadioxabicyclooctane
are
presented
in
Table
3.

Table
3.1
Toxicological
Endpoints
for
Assessing
Occupational
and
Residential
Exposures/
Risks
of
Azadioxabicyclooctane
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Dietary
Risk
Assessments
Acute
Dietary
(
general
population)
NOAEL
=
10.6
mg/
kg/
day
UF
=
100
FQPA
SF
=
10x
aPAD
=
acute
RfD
FQPA
SF
=
0.01
mg/
kg/
day
90
day
oral
toxicity
in
rats
LOAEL
=
10.6
mg/
kg/
day
based
on
decreased
water
consumption
at
56.5
mg/
kg/
day
in
males.

Acute
Dietary
(
females
13
and
over)
NOAEL
=
10.6
mg/
kg/
day
UF
=
100
FQPA
SF
=
10x
aPAD
=
acute
RfD
DB
UF
=
0.01
mg/
kg/
day
90
day
oral
toxicity
in
rats
LOAEL
=
10.6
mg/
kg/
day
based
on
decreased
water
consumption
at
56.5
mg/
kg/
day
in
males.

Chronic
Dietary
(
all
population)
NOAEL
=
10.6
mg/
kg/
day
UF
=
300
FQPA
SF
=
10x
cPAD
=
chronic
RfD
FQPA
SF
=
0.003
mg/
kg/
day
90
day
oral
toxicity
in
rats
LOAEL
=
10.6
mg/
kg/
day
based
on
decrease
water
consumption
at
56.5
mg/
kg/
day
in
males.

Short­
Term
(
1
to
30
days)
Intermediate­
Term
Incidental
Oral
(
1
to
6
months)
No
endpoints
required
Non­
Dietary
Risk
Assessments
Dermal
(
all
durations)
a
Dermal
LOAEL
=
100
mg/
kg/
day
Short­
Term
and
Intermediate­
Term
=
300
Occupational
Long­
Term
MOE
=
1,000
Co­
critical
studies;

21­
day
dermal
toxicity
in
rats
LOAEL=
100
mg/
kg/
day
(
severe
dermal
effects)

developmental
toxicity
in
rats
LOAEL
=
100
mg/
kg/
day
(
severe
dermal
effects
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
14
of
33
Inhalation
(
all
durations)
b
90­
day
oral
study
NOAEL
=
10.6
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
MOE
=
3000
90
day
oral
toxicity
in
rats
LOAEL
=
10.6
mg/
kg/
day
based
on
decreased
water
consumption
at
56.5
mg/
kg/
day
in
males.

Cancer
(
oral,
dermal,
inhalation)
No
cancer
data
available
Notes:
UF
=
uncertainty
factor;
FQPA
SF
=
Special
FQPA
safety
factor;
NOAEL
=
no
observed
adverse
effect
level,;
LOAEL
=
lowest
observed
adverse
effect
level;
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic);
RfD
=
reference
dose;
MOE
=
margin
of
exposure
Dermal
absorption
factors
were
not
needed.
Inhalation
absorption
factors
were
not
provided;
therefore
a
conservative
assumption
of
100%
absorption
was
assumed.

*
The
Special
FQPA
Safety
Factor
recommended
by
the
ADTC
assumes
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degredates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.
(
April
26,
2005)

a:
For
the
dermal
MOE
(
ST
and
IT),
the
value
of
300
is
derived
from
10x
interspecies
variation,
10x
intraspecies
extrapolation,
and
3x
for
the
use
of
a
LOAEL
for
both
occupational
and
residential
exposure.
For
the
Occupational
Long
Term
assessment,
the
target
MOE
of
1,000
is
derived
from
the
10x
interspecies
variation,
10x
intraspecies
extrapolation,
and
3
x
for
the
use
of
a
LOAEL,
and
3x
for
extrapolating
a
short­
term
study
to
a
chronic
scenario
for
both
occupational
and
residential
exposure.
b:
For
the
inhalation
MOE
of
3,000
for
all
durations,
the
value
was
dervived
from
a
10x
interspecies
variation,
10x
intraspecies
extrapolatioin,
and
3x
for
database
for
both
occupational
and
residential
exposure;
an
additional
10x
route­
to­
route
extrapolation
is
used
to
determine
if
an
inhalation
toxicity
study
is
warranted.

Table
3.2
Acute
Toxicity
of
Azadioxabicyclooctane
Guideline
No.
Study
Type
MRID
#(
S)
Results
Toxicity
Category
81­
1
Acute
Oral
41641601
LD50
=
1940
mg/
kg
III
81­
2
Acute
Dermal
41671801
LD50
>
2,000
mg/
kg
III
81­
3
Acute
Inhalation
42650901
LC50
=
>
0.441
mg/
L
II
81­
4
Primary
Eye
Irritation
41641602
severe
irritant
I
81­
5
Primary
Skin
Irritation
41641603
moderate
irritant
III
81­
6
Dermal
Sensitization
assumed
sensitizer
no
data
available
3.3
FQPA
Considerations
The
ADTC
(
Antimicrobial
Division
Toxicology
Committee)
recommended
that
the
special
10x
hazard­
based
safety
factor
under
the
FQPA
be
retained
(
10x)
for
azadioxabicyclooctane.
There
is
only
one
prenatal
dermal
developmental
toxicity
study
available
for
azadioxabicyclooctane
and
there
is
no
reproductive
toxicity
information
or
studies.
While
the
developmental
study
showed
no
evidence
of
susceptibility
of
offspring
to
this
chemical,
the
route
of
administration
is
not
a
good
indicator
of
potential
effects
from
oral
exposures.
In
addition,
as
Page
15
of
33
noted
above,
information
on
the
test
article
characterization
is
not
resolved
at
this
time.
The
retention
of
the
10x
FQPA
hazard­
based
factor
is
consistent
with
the
Agency's
published
guidance
(
http://
www.
epa.
gov/
oppfead1/
trac/
science/
determ.
pdf)

4.0
RESIDENTIAL
EXPOSURE
ASSESSMENT
4.1
Summary
of
Registered
Uses
The
exposure
scenarios
identified
for
residential
handlers
are
airless
spraying
and
brush
painting,
both
of
which
arise
as
a
result
of
the
chemical
being
incorporated
as
a
material
preservative
into
paints.
The
application
rates
for
the
potential
uses
of
azadioxabicyclooctane
and
the
quantity
handled
are
presented
in
Table
4.1.
The
rates
that
are
provided
in
the
table
are
the
%
product
by
weight
of
material
treated,
along
with
the
%
a.
i.
by
weight
of
material
treated
in
parentheses.
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
that
may
occur
when
an
individual
uses
any
of
the
other
end
use
products
on
label
1529­
28
(
i.
e:
caulks,
inks,
sealants).
Therefore,
residential
handler
exposures
were
assessed
for
the
application
of
paint,
as
this
scenario
represents
maximum
possible
exposure
to
the
chemical.
Also,
it
is
important
to
note
that
label
1529­
28
restricts
the
textile
fiber
finish
use
of
azadioxabicyclooctane
to
fibers
that
are
not
in
direct
contact
with
the
skin,
and
for
this
reason,
the
textile
exposure
was
not
assessed
for
the
residential
setting.

Table
4.1.
Use
Rates
for
Handler
Exposures
for
Azadioxabicyclooctane
Use
Method
of
Application
Substrate
Treated/
Handled
through
Exposure
Scenario
Application
Rate
%
product
by
weight
of
material
treated
(%
a.
i.
)

Maxa
Recommended
Mina
Materials
Preservative
Airless
spraying
Latex
Paint
0.5
(
0.25)
0.1
(
0.05)

Brush
Painting
Latex
Paint
0.5
(
0.25)
0.1
(
0.05)

a:
The
recommended
maximum
and
minimum
use
levels
are
assessed
because
in
some
cases,
the
application
rate
of
0.25%
a.
i.
by
weight
of
material
treated
generates
an
MOE
of
concern,
whereas
using
materials
treated
at
the
minimum
application
rate
of
0.05%
a.
i.,
an
MOE
that
is
not
of
concern
is
generated.

4.2
Dietary
Exposure/
Risk
Pathway
4.3
Drinking
Water
Exposure/
Risk
Pathway
4.4
Residential
Exposure/
Risk
Pathway
4.4.1
Residential
Handler
Exposure
Through
using
Equations
1­
3
in
section
1.2
(
Criteria
for
Conducting
Exposure
Assessment),
the
daily
dose
(
dermal
and
inhalation),
and
MOEs
for
short­
term
were
Page
16
of
33
calculated.
These
are
presented
in
Table
4.2.
Page
17
of
33
Table
4.2:
Short
Exposures
and
MOEs
for
Residential
Uses
of
Azadioxabicyclooctane
Exposure
Scenario
Method
of
Application
Unit
Exposure
Application
rate
(%
a.
i.
by
weight
of
material
being
treated
)
Quantity
of
treated
material
handled
per
day
(
lbs)
Daily
Dose
(
mg
a.
i./
kg
per
day)
g
MOE
h
Dermal
Unit
Exposure
(
mg/
lb
a.
i.)
Inhalation
Unit
Exposure
(
mg/
lb
a.
i.)
Dermal
Dose
Inhalation
Dose
Dermal
(
target
=
300)
Inhalation
(
target
=
3000)

Paints
Brush/
Roller
230a
0.280c
0.25%
(
max)
20e
(
2
gallons)
0.1643
0.0002
609
53,000
Airless
Sprayer
79b
0.83d
0.25%
(
max)
150
f
(
15
gallons)
0.4232
0.004446
236
2.400
Airless
Sprayer
79b
0.83d
0.05%
(
min)
i
150
f
(
15
gallons)
0.0846
0.000889
1,181
12,000
a,
c:
The
Unit
Exposures
for
the
brush/
roller
scenario
are
from
the
Residential
SOP's
for
paintbrush
application.

b,
d:
The
Unit
Exposures
for
the
airless
sprayer
scenario
are
from
the
Residential
SOP's
for
the
airless
spraying
application.

e:
This
value
is
from
the
AD
SOP
section
titled
Residential
Handlers
in
which
the
quantity
used
for
the
paintbrush/
roller
application
is
assumed
to
be
2
gallons
(
90th
percentile
value
of
8
gallons
of
latex
paint
used
per
year
divided
by
the
mean
frequency
of
4
painting
events/
year).
As
a
result,
2
gallons
paint
preserved/
day
x
10
lb/
gal
paint
(
density
of
paint)
=
20
lbs
of
treated
paint
handled.

f:
This
value
is
from
the
AD
SOP
section
titled
Residential
Handlers
in
which
the
quantity
used
for
the
airless
spraying
application
is
assumed
to
be
15
gallons
(
based
on
coverage
of
200ft2/
gal
and
house
size
of
40
x
30
x
20
ft
(
surface
area
of
2,800ft2)).
The
density
of
paint
is
assumed
to
be
10
lb/
gal,
so
that
15
gallons
x
10
lb/
gal
=
150
lbs
of
treated
paint
handled.

g:
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Unit
Exposure
(
mg/
lb
a.
i.)
x
rate
x
amount
handled
x
(
1/
body
weight
(
kg))

h:.
MOE
=
Toxicity
Endpoint
(
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day);
where
dermal
NOAEL
=
100
mg/
kg/
day
and
the
inhalation
LOAEL
=
10.6
mg/
kg/
day
i:
The
minimum
application
rate
of
0.1
%
product
by
weight
of
the
latex
paint
treated
was
assessed
because
the
inhalation
MOE
for
the
airless
sprayer
application
was
of
concern
for
a
painter
using
the
paint
that
has
been
treated
at
the
maximum
allowable
rate.
Page
18
of
33
4.4.1.1
Painter
Exposure
The
target
dermal
MOE's
that
are
used
in
this
assessment
are
300
for
short
term/
intermediate
term
exposures
(
ST/
IT)
and
for
inhalation
exposures,
the
target
MOE
for
all
durations
is
3000.
These
target
MOEs
are
compared
to
those
calculated
in
Table
4.2.

°
Brush/
Roller:
The
dermal
and
inhalation
unit
exposures
for
this
application
method
were
obtained
from
1197
HED
Residential
SOPs.
The
dermal
unit
exposure,
230
mg/
lb
a.
i.
is
representative
of
the
handler
a
t­
shirt
and
shorts
while
applying
the
paint
with
a
brush,
and
without
gloves
because
this
is
a
residential
use
site.
The
inhalation
unit
exposure,
0.280
mg/
lb
a.
i.,
is
representative
of
a
painter
applying
paint
with
a
brush.
The
maximum
application
rate,
as
stated
on
the
label
(#
1529­
28)
is
0.5%
product
by
weight
of
material
being
treated.
The
application
rates
on
the
label
do
not
account
for
the
product
containing
only
50%
a.
i.,
so
the
maximum
application
results
in
exposure
to
0.25%
a.
i.
by
weight
of
the
material
treated.

For
this
scenario,
the
painter
is
expected
to
handle
2
gallons
of
paint
per
day.
This
is
from
the
AD
Residential
SOPs
(
1997
&
2001)
in
which
this
value
is
the
90th
percentile
value
of
8
gallons
of
latex
paint
used
per
year
divided
by
the
mean
frequency
of
4
painting
events
per
year.
The
density
of
paint
is
assumed
to
be
10
lb/
gallons,
so
that
the
value
of
2
gallons
is
equivalent
to
20
lbs
of
paint.
The
daily
doses
are
calculated
with
Equation
2
and
using
a
body
weight
of
70
kg.
The
daily
doses
and
toxicity
endpoints
(
Table
3.1)
were
used
to
calculate
the
MOEs
(
Equation
3).

When
a
painter
uses
paint
that
is
treated
at
the
maximum
application
rate
of
0.25%
a.
i.
by
weight,
the
dermal
MOE
is
609.
There
is
no
concern
with
short
term
exposure
because
this
is
greater
than
the
target
MOE
of
300.
There
is
also
no
concern
with
the
inhalation
exposure
to
paint
treated
that
has
been
treated
at
the
maximum
allowable
rate
of
0.5%
product
(
0.25%
a.
i.)
by
weight
of
the
paint
treated.
The
target
inhalation
MOE
is
3000,
and
the
calculated
MOE
is
53,000.

°
Airless
Sprayer:
The
dermal
and
inhalation
unit
exposures
for
this
application
method
were
obtained
from
the
1997
HED
Residential
SOPs.
The
dermal
unit
exposure,
79
mg/
lb
a.
i.
is
representative
of
the
handler
wearing
a
t­
shirt
and
shorts
while
performing
an
ungloved
airless
spray
application.
The
inhalation
unit
exposure,
0.83
mg/
lb
a.
i.,
is
representative
of
a
painter
applying
a
material
with
an
airless
sprayer.
The
maximum
application
rate,
as
stated
on
the
label
is
0.5%
product
by
weight
of
material
being
treated,
and
the
minimum
is
0.1
%
product
by
weight
of
material
being
treated.
These
application
rates
do
not
account
for
the
product
containing
only
50%
a.
i.,
so
the
maximum
application
results
in
exposure
to
0.25%
a.
i.
by
weight
of
material
treated
and
the
minimum
application
results
in
0.05%
a.
i.
by
weight
of
material
treated.

For
this
scenario,
the
painter
is
expected
to
handle
15
gallons
of
paint
per
day.
This
is
from
the
AD
SOP's
in
which
this
value
is
based
on
coverage
of
200ft2/
gal
and
a
house
size
being
40'
x
30'
x
20'
(
surface
area
of
2,800ft2).
The
density
of
paint
is
assumed
to
be
Page
19
of
33
10
lb/
gallons,
so
that
the
value
of
15
gallons
is
equivalent
to
150
lbs
of
paint.
The
daily
doses
are
calculated
with
Equation
2
using
a
body
weight
of
70
kg.
The
daily
doses
and
toxicity
endpoints
(
Table
3)
were
used
to
calculate
the
MOEs
(
Equation
3).

When
a
painter
uses
paint
that
is
treated
at
the
maximum
application
rate
of
0.25%
a.
i.
by
weight,
there
is
concern
with
both
dermal
and
inhalation
exposures.
The
dermal
MOE
is
236,
which
is
less
than
300.
The
target
inhalation
MOE
is
3000,
and
when
a
painter
uses
paint
that
is
treated
at
this
rate,
the
inhalation
MOE
is
2,400.
As
a
result,
the
risk
associated
with
a
painter
using
paint
treated
at
the
minimum
application
rate
of
0.1%
product
(
0.05%
a.
i.)
by
weight
of
the
paint
treated
was
assessed.
The
dermal
MOE
for
this
minium
rate
is
1,181,
which
is
greater
than
the
target
MOE
of
300,
and
likewise,
the
inhalation
MOE
is
12,000,
which
is
greater
than
3,000.

The
method
of
airless
spraying
will
not
present
any
dermal
or
inhalation
concern
if
the
paint
that
is
used
has
been
treated
at
the
rate
of
0.1%
product
(
0.05%
a.
i.)
by
weight
of
paint
treated.

4.4.2
Residential
Post
Application
Exposure
Residential
post
application
exposures
occur
when
bystanders
contact
areas
in
which
the
antimicrobial
end
use
product
has
recently
been
applied.
For
azadioxabicyclooctane
there
are
no
potential
dermal
post
application
exposures
to
assess.
As
for
inhalation
post
application
exposures,
these
are
expected
to
be
minimal
because
the
paint
is
dry
and
the
vapor
pressure
of
azadioxabicyclooctane
is
negligible.

4.5
Data
Limitations/
Uncertainties
Currently,
azadioxabicyclooctane
chemical­
specific
handler
or
postapplication
exposure
studies
that
meet
Agency
guidelines
have
not
been
identified.
Surrogate
dermal
and
inhalation
data
from
the
PHED
database
were
used
to
assess
residential
handler
exposure.

The
following
factors
concerning
PHED
and
the
AD
residential
SOPs
should
also
be
noted:

C
The
job
functions
where
pesticides
are
commonly
used
may
be
different
from
those
job
functions
where
antimicrobial
chemicals
are
used
(
i.
e.,
representativeness
issue).

C
The
basic
assumption
underlying
the
PHED
database
is
that
exposure
to
pesticide
handlers
is
primarily
a
function
of
the
physical
parameters
associated
with
handling
and
applying
of
the
product
rather
than
the
chemical
properties
of
the
individual
active
ingredients.
Therefore
it
is
important
to
recognize
the
potential
effects
the
chemical
properties
of
azadioxabicyclooctane
may
have
on
exposure
rates.
Page
20
of
33
°
No
information
regarding
the
amount
end
use
product
handled
daily
was
provided
by
the
registrant.
The
AD
SOP
was
used
for
developing
a
value
to
use
in
the
assessment.

°
Any
changes
to
the
toxicological
endpoints
will
need
to
be
incorporated
into
this
review.

5.0
RESIDENTIAL
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
There
is
no
need
for
a
residential
aggregate
risk
assessment/
characterization
for
azadioxabicyclooctane.

6.0
OCCUPATIONAL
EXPOSURE
AND
RISK
6.1
Occupational
Handlers
The
exposure
scenarios
identified
for
occupational
workers
are
the
liquid
pour
and
liquid
pump
applications
of
this
chemical
when
it
is
used
as
a
preservative
for
the
label­
specified
materials.
There
are
also
occupational
painter
scenarios
(
which
result
from
the
chemical
being
incorporated
as
a
preservative
into
paints)
that
involve
the
methods
of
applications
of
airless
spraying
and
brush
painting.
The
use
rates
(
maximum
and
minimum)
for
all
potential
uses
of
azadioaxabicyclooctane,
and
the
assumptions
used
to
calculate
them,
are
presented
in
Table
6.1.
The
rates
that
are
provided
in
the
table
are
the
%
product
by
weight
of
material
treated,
along
with
the
%
a.
i.
by
weight
of
material
treated
in
parentheses.
Page
21
of
33
Table
6.1.
Representative
Exposure
Scenarios
Associated
with
Occupational
Exposure
to
Azadioxabicyclooctane
Assessed
in
this
Document
Uses
Method
of
application
Application
Rate
%
product
by
weight
of
material
treated
(%
a.
i.
)

Maximum
a
Minimum
b
Material
Preservatives
Adhesives
(
synthetic
and
naturalbased

Liquid
Pour
Liquid
Pump
0.5
(
0.25)
0.1
(
0.05)
d
Caulks
0.5
(
0.25)
0.1
(
0.05)

Drilling
muds
0.5
(
0.25)
0.05
(
0.025)

Flooding
fluids
0.5
(
0.25)
0.01
(
0.005)

Latex
emulsions
0.5
(
0.25)
0.5
(
0.025)

Ink
dispersions
0.5
(
0.25)
0.1
(
0.05)

Paper
coatingsc
0.5
(
0.25)
0.1
(
0.05)

Pigment
dispersions
0.5
(
0.25)
0.1
(
0.05)

Pigment
slurry
0.5
(
0.25)
0.05
(
0.025)

Wax
emulsions
0.5
(
0.25)
0.05
(
0.025)

Textilese
0.5
(
0.25)
0.05
(
0.025)

Sealants
0.5
(
0.25)
0.1
(
0.05)

Metal
working
fluids
Liquid
Pour
Liquid
Pump
0.3
(
0.15)
0.1
(
0.05)

Latex
Paint
Liquid
Pour
Liquid
Pump
Airless
Spray
Brush/
Roller
Application
0.5
(
0.25)
0.1
(
0.05)

a:
Maximum
makes
reference
to
the
label,
which
states,
"
the
maximum
level
permitted
for
all
other
applications
listed
[
other
than
metal
working
fluids]
is
0.5%
[
product
by
weight
of
material
to
be
treated]."
The
product
contains
50%
a.
i,
and
the
rates
in
parentheses
reflect
the
%
a.
i.
by
weight
of
the
material
to
be
treated.

b:
The
minimum
use
rate
is
also
included,
because
in
some
cases,
the
recommended
maximum
rate
generates
an
MOE
of
concern
as
well.

c:
The
discrepancy
on
label
1529­
28
needs
to
be
clarified
as
to
whether
or
not
azadioxabicyclooctane
is
used
for
pulp
and
paper
or
for
paper
coatings
because
both
of
these
uses
are
on
the
label,
but
a
rate
is
only
provided
for
the
paper
coating
use.

d:
The
natural
based
adhesives
have
a
minimum
use
rate
of
0.2%,
and
the
synthetic
adhesives,
0.1%.
The
synthetic
adhesive
minimum
rate
is
used
as
the
representative
rate.

e:
The
label,
Reg
#
1529­
28,
indicates
that
the
textile
use
is
only
permitted
for
fibers
that
do
not
come
into
direct
contact
with
the
skin
Page
22
of
33
6.1.1
Occupational
Worker:

The
representative
scenarios
derived
from
Table
6.1
have
been
assessed
by
using
equations
1­
3
from
Section
1.2,
titled
"
Criteria
For
Conducting
Exposure
Assessment."
From
this,
the
daily
dose
(
dermal
and
inhalation),
and
MOEs
for
short­
term
and
intermediate
term
were
all
calculated.
The
exposures
and
MOEs
are
presented
in
Table
6.2.
Per
label
discretion,
it
is
required
that
the
user
wears
gloves
when
handling
this
chemical
and
the
unit
exposures
applied
in
this
occupational
assessment
reflect
this.
It
is
assumed
that
exposures
while
treating
latex
paints
will
be
equal
to
or
greater
than
exposures
that
may
occur
when
an
individual
uses
NUOSEPT
for
treatment
of
adhesives,
caulks,
ink
dispersions,
pigment
dispersions,
pigment
slurry,
wax
emulsions,
and
sealants
because
the
application
rate,
unit
exposures,
and
quantity
handled
will
be
the
same
as
that
for
latex
paints.
In
addition,
the
preservation
of
paper
coatings
and
metalworking
fluids
were
assessed
separately
because
of
the
difference
in
application
rate,
unit
exposures,
and
quantity
handled.
The
density
of
azadioxabicyclooctane
is
9.55
lb/
gal
as
discussed
in
Section
1.4,
Physical/
Chemical
Properties.
In
the
sections
throughout
the
table
where
it
is
indicated
that
the
product
is
used
in
the
manufacturing
process,
this
density
was
used
to
convert
from
gallons
to
pounds
in
the
column
labeled
"
Quantity
Handled/
Treated
per
day".
However,
for
the
uses
where
it
is
indicated
that
exposure
to
azadioxabicyclooctane
results
from
either
airless
spraying
or
brush/
roller
application
of
paint,
the
density
of
paint
was
used,
which
is
10
lb/
gallon.
Page
23
of
33
Table
6.2:
Short
and
Intermediate
Term
Azadioxabicyclooctane
Exposures
and
MOE's
Associated
with
Occupational
Handlers
a
Substrate
Treated/
Handled
through
Exposure
Scenario
Method
of
Application
Application
rate
(%

a.
i.
by
weight
of
material
being
treated)
Unit
Exposure
Quantity
Handled/
Trea
ted
per
day
(
unit
as
indicated)
p
Daily
Dose
(
mg
a.
i./
kg
per
day)
q
MOEr
Dermal
Unit
Exposure
(
mg/
lb
a.
i.)
Inhalation
Unit
Exposure
(
mg/
lb
a.
i.)
Dermal
Dose
Inhalation
Dose
Dermal
(
target
ST/
IT
MOE
=
300)
Inhalation
(
target
MOE
=

3,000)

Latex
Paint
(
Latex
Emulsions)
s
Liquid
Pour
(
preservation)
0.25
(
max)
0.135b
0.00346c
19,100
lbs
(
2,000
gallons)
0.0921
0.00236
1,100
4,500
Liquid
Pump
(
preservation)
0.25
(
max)
0.00629d
0.000403e
191,000
lbs
(
20,000
gallons)
0.0429
0.00275
2,300
3,800
Airless
spraying
(
end
user)
0.25
(
max)
14f
0.83g
500
lbs
(
50
gallons)
0.25
0.0148
400
720
Airless
spraying
(
end
user)
0.05
(
min)
14f
0.83g
500
lbs
(
50
gallons)
0.05
0.00296
2,000
3,600
Brush
Painting
(
end
user)
0.25
(
max)
24h
0.28i
50
lbs
(
5
gallons)
0.0429
0.0005
2,300
21,000
Metalworking
cutting
fluids
(
preservation)
Liquid
Pour
0.15
(
max)
0.184j
0.00854k
2,865
lbs
(
300
gallons)
0.0113
0.000524
8,900
20,000
Liquid
Pump
0.15
(
max)
0.312l
0.00348m
2,865
lbs
(
300
gallons)
0.0192
0.000214
5,200
50,000
Paper
Coating
(
preservation)
Liquid
Pump
0.25
(
max)
0.00454n
0.000265o
9,550
lbs
(
1000
gallons)
0.0015
0.000090
65,000
120,000
Substrate
Treated/
Handled
through
Exposure
Scenario
Method
of
Application
Application
rate
a.
i.
by
weight
of
material
being
treated)
Unit
Exposure
Quantity
Handled/
Trea
ted
per
day
(
unit
as
indicated)
p
Daily
Dose
(
m
day)
q
Dermal
Unit
Exposure
(
mg/
lb
a.
i.)
Inhalation
Unit
Exposure
(
mg/
lb
a.
i.)
Dermal
Dose
Inhalation
Dose
Page
24
of
33
Drilling
Muds
(
end
user)

Flooding
Fluids
(
end
user)
Liquid
Pourt
0.25
(
max)
0.135b
0.00346c
46.7
lbs
(
5.6
gal
(
ST))
0.0002
0.00
23.3
lbs
(
2.8
gal
(
IT))
0.0001
0.00
a:
The
maximum
application
rate
of
0.5%
product
(
0.25%
a.
i).
by
weight
of
material
treated
generates
an
MOE
of
concern,
whereas
using
materials
treated
at
the
minimum
application
rates
specified
in
the
table,
an
MOE
that
is
not
of
concern
is
generated.
All
of
these
uses
in
Table
6.2
were
assessed
at
this
rate,
except
for
metalworking
fluids.
This
treatment
was
label
specified
to
be
0.3
%
product
(
0.15%
a.
i.)
by
weight
of
the
fluid
treated.

b,
c
:
CMA
preservative
liquid
pour,
gloved
values
for
dermal
and
inhalation
are
0.135
mg/
lb
a.
i.
and
0.00346
mg/
lb
a.
i.,
respectively.

d,
e
:
CMA
preservative
liquid
pump,
gloved
values
for
dermal
and
inhalation
are
0.00629
mg/
lb
a.
i.
and
0.000403
mg/
lb
a.
i.,
respectively.

f,
g
:
PHED
unit
exposure
values
for
a
handler
wearing
gloves
and
applying
paint
using
an
airless
sprayer
were
used,
so
that
the
dermal
and
inhalation
values
were
14
mg/
lb
a.
i.
and
0.830
mg/
lb
a.
i.,
respectively.

h,
i
:
PHED
paintbrush
application
scenario,
gloved
values
for
dermal
and
inhalation
are
24
mg/
lb
a.
i.
and
0.28
mg/
lb
a.
i.,
respectively.

j,
k
:
CMA
MWF
liquid
pour,
gloved
values
for
dermal
and
inhalation
are
0.184
mg/
lb
a.
i.
and
0.00854
mg/
lb
a.
i.,
respectively
l,
m
:
CMA
MWF
liquid
pump,
gloved
values
for
dermal
and
inhalation
are
0.312
mg/
lb
a.
i.
and
0.00348
mg/
lb
a.
i.,
respectively
n,
o
:
CMA
liquid
pump
for
pulp
and
paper,
gloved
values
for
dermal
and
inhalation
are
0.0045
mg/
lb
a.
i.
and
0.00027
mg/
lb
a.
i.,
respectively.

p:
For
the
quantity
handled,
it
is
explained
in
the
MOE
discussion
following,
which
addresses
each
scenario
individually
q:
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Unit
Exposure
(
mg/
lb
a.
i.)
x
rate
x
amount
handled
x
(
1/
body
weight
(
kg))

r:
MOE
=
Toxicity
Endpoint
(
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day);
where
dermal
NOAEL
=
100
mg/
kg/
day
and
the
inhalation
LOAEL
=
10.6
mg/
kg/
day
s:
Latex
paints
are
representative
for
adhesives,
caulks,
ink
dispersions,
pigment
dispersions,
pigment
slurries,
wax
emulsions,

textiles,
and
sealants.

t:
There
is
a
chemical
metering
application
(
i.
e.
liquid
pump)
for
drilling
muds
and
flooding
fluid
uses.
However,
this
was
not
assessed
because
appropriate
unit
exposure
values
are
not
available.
This
is
further
discussed
in
the
End
User
discussion
later
in
the
document.
Page
25
of
33
The
target
dermal
MOEs
that
are
used
in
this
assessment
are
300
for
both
short
term
and
intermediate
term
exposures
(
ST/
IT).
As
for
inhalation,
the
target
MOE
for
all
durations
of
exposures
is
3000.
These
target
MOEs
are
compared
to
those
calculated
in
Table
6.2
for
each
individual
exposure
scenario.

6.1.1.1
Occupational
Handler
For
all
the
use
scenarios,
the
label
(#
1529­
28)
requires
that
gloves
are
to
be
worn
when
using
handling
this
preservative.

Painter
The
painter
can
come
into
contact
with
paints
that
have
been
treated
with
azadioxabicyclooctane.
This
is
either
through
applying
the
paint
by
airless
spraying
or
brush/
roller
painting.

°
The
daily
amount
of
paint
handled
for
an
airless
sprayer
application
that
was
used
in
this
assessment
was
based
on
the
AD
residential
SOPs
for
commercial
painters
that
apply
the
already
treated
paint
through
airless
spraying.
The
amount
in
the
SOP
is
50
gallons.
Based
on
these
estimates,
1.25
lbs
of
a.
i.
is
handled
per
day
if
the
painter
is
applying
the
paint
using
a
spray
application
(
i.
e.,
50
gal
paint/
day
x
0.5%
product
x
10
lb/
gal
(
density
of
paint)
paint
x
50%
ai
in
product).

Chemical­
specific
exposure
data
were
not
submitted
to
support
the
airless
spraying
use.
Therefore,
the
AD
has
developed
a
screening­
level
assessment
using
surrogate
data
to
determine
the
potential
risks
associated
with
this
method
of
application.
The
most
representative
data
available
for
open
pouring
and
airless
spraying
are
the
Pesticide
Handlers
Exposure
Database
(
PHED).
The
airless
spraying
dermal
UE
is
14
mg/
lb
a.
i.,
where
test
subjects
were
wearing
a
single
layer
of
clothing
and
gloves.
The
inhalation
UEs
for
airless
spraying
is
0.83
mg/
lb
a.
i..

The
dermal
MOE
for
the
airless
spraying
at
the
application
rate
of
0.5%
product
(
0.25%
a.
i.)
by
weight
of
material
treated
is
400.
This
is
not
of
concern
for
ST/
IT
exposure,
since
it
is
greater
than
the
target
MOE
of
300.

The
inhalation
MOE
at
the
application
rate
of
0.5%
product
(
0.25%
a.
i.)
by
weight
of
material
treated
is
720,
which
is
of
concern
because
it
is
less
than
3,000.
The
label
indicates
a
minimum
application
rate
of
0.1%
product
(
0.05%
a.
i.)
by
weight
of
the
material
treated,
and
the
MOE
was
calculated
for
a
painter
using
paint
treated
at
this
minimum
rate,
which
is
3,600.
This
is
not
of
concern
for
inhalation
exposure.
The
method
of
airless
spraying
will
not
pose
any
concerns,
dermal
or
inhalation
if
the
paint
that
is
used
has
been
treated
at
the
rate
of
0.1%
product
(
0.05%
a.
i.)
by
weight
of
paint
treated.
Page
26
of
33
°
The
daily
amount
of
paint
handled
for
a
brush/
roller
application
that
was
used
in
this
assessment
was
based
on
the
AD
residential
SOPs
use
table
for
commercial
painters
that
apply
the
already
treated
paint
through
a
brush/
rolling
application.
The
amount
in
the
SOP
is
5
gallons.
Based
on
these
estimates,
0.125
lbs
of
a.
i.
is
handled
per
day
(
i.
e.,
5
gal
paint/
day
x
0.5%
product
x
10
lb/
gal
(
density
of
paint)
x
50%
a.
i.
in
product).

Chemical­
specific
exposure
data
were
not
submitted
to
support
the
brush
painting/
roller
use.
Therefore,
the
AD
has
developed
a
screening­
level
assessment
using
surrogate
data
to
determine
the
potential
risks
associated
with
this
method
of
application.
The
most
representative
data
available
for
this
application
is
the
Pesticide
Handlers
Exposure
Database
(
PHED).
The
brush
painting
dermal
UE
is
24
mg/
lb
a.
i.,
where
test
subjects
were
wearing
a
single
layer
of
clothing
and
gloves.
The
inhalation
UE
for
brush
painting
is
0.28
mg/
lb
a.
i..

The
dermal
MOE
for
the
brush/
roller
application
at
the
treated
rate
of
0.5%
product
is
2,300.
This
is
not
of
concern
for
ST/
IT
or
LT
exposure,
since
it
is
greater
than
the
target
MOEs
of
300
and
1,000.
The
inhalation
MOE
is
21,000,
which
is
well
above
3,000
and
is
not
of
concern.

Manufacturer/
Materials
Preservative
Handler:

°
The
worker
can
come
into
contact
with
the
preservative
when
it
is
being
incorporated
into
the
latex
paint
during
manufacturing
(
pour
or
pump).
The
volume
of
preservative
handled
can
greatly
vary
depending
on
the
manufacturers'
size
and
sophistication.
The
high­
volume
manufacturer
could
produce
two
10,000
gallon
batches
in
an
8­
hour
day
where
the
liquid
materials
such
as
the
biocide
would
be
automatically
pumped
into
the
batch.
Therefore,
a
high­
volume
manufacturer
could
produce
approximately
20,000
gallons
of
product
(
i.
e.
paints)
in
one
day.
The
lower­
volume
manufacturer
could
make
four
500
gallon
batches
in
an
8­
hour
day
where
the
liquid
materials
such
as
the
biocide
could
be
hand
metered
in
or
put
in
via
5
gallon
buckets.
Therefore,
a
lower­
volume
manufacturer
could
produce
approximately
2,000
gallons
of
product
(
i.
e.,
protective
colloids,
emulsion
resins,
water­
thinned
paints,
etc.)
in
one
day.
Based
on
these
estimates,
47.75
lb
a.
i./
day
could
be
handled
by
workers
utilizing
open
pour
techniques
(
i.
e.,
2,000
gal
coating
preserved/
day
x
0.5%
product
x
9.55
lb/
gal
(
product
density)
x
50%
a.
i.
in
product),
while
477.5
lb
ai/
day
could
be
handled
by
workers
utilizing
chemical
metering
techniques
(
i.
e.,
20,000
gal
coating
preserved/
day
x
0.5%
product
x
9.55
lb/
gal
(
product
density)
x
50%
a.
i.
in
product).
The
density
value
of
9.55
lb/
gal
is
the
density
of
the
product,
NUOSEPT,
per
label
1529­
28.

The
potential
for
occupational
exposure
is
based
on
the
loading
of
the
product
by
open
pouring
or
connecting/
disconnecting
the
chemical
metering
pump.
Chemicalspecific
exposure
data
were
not
submitted
to
support
the
materials
preservative
use.
Therefore,
the
AD
has
developed
a
screening­
level
assessment
using
surrogate
data
to
determine
the
potential
risks
associated
with
the
materials
Page
27
of
33
preservative
use.
The
most
representative
data
available
for
open
pouring
and
chemical
metering
pump
for
industrial
uses
are
the
monitoring
data
from
the
CMA
Antimicrobial
Exposure
Assessment
Study.
The
liquid
open
pour
and
liquid
pump
data
from
the
preservative
loading
are
used
to
develop
the
screening­
level
assessment.
The
dermal
UEs
of
0.135
mg/
lb
a.
i.
for
liquid
open
pour
and
0.00629
mg/
lb
a.
i.
for
liquid
pump
are
both
based
on
only
2
replicates
where
the
test
subjects
were
wearing
a
single
layer
of
clothing
and
chemical
resistant
gloves
(
UE
are
not
available
for
the
"
no
glove"
scenarios).
The
inhalation
UEs
are
based
on
the
same
2
replicates.
The
inhalation
UE
for
open
pour
is
0.00346
mg/
lb
a.
i.
and
the
UE
for
liquid
pump
is
0.000403
mg/
lb
a.
i..
Although
these
exposure
scenarios
are
based
on
minimal
replicates,
the
exposure
values
are
similar
to
those
found
in
PHED
for
similar
scenarios.

The
dermal
MOEs
for
both
methods
of
application,
liquid
pour
and
pump,
are
not
of
concern.
They
are
1,100
and
2,300
respectively.
Both
of
these
values
are
greater
than
the
target
MOE
of
300.
In
addition,
the
inhalation
MOEs
for
both
methods
of
applications
do
not
pose
a
concern.
They
are
4,500
(
pour)
and
3,800
(
pump),
both
of
which
are
greater
than
the
inhalation
target
MOE
of
3,000.

°
For
paper
coatings
it
was
conservatively
assumed
based
on
AD's
communication
with
experts
in
the
industry
that
1,000
gallons
of
paper
making
chemicals
could
be
preserved
each
day.
Thus,
for
the
use
of
azadioxabicyclooctane
in
paper
making
chemicals,
the
amount
of
ai
handled
through
chemical
metering
pump
use
on
a
daily
basis,
23.87
lb
a.
i./
day
was
estimated
(
i.
e.,
1000
gal
preserved/
day
x
0.5%
product
x
9.55
lb/
gal
(
product
density)
x
50
%
a.
i.
in
product)

The
potential
for
occupational
exposure
was
based
on
the
loading
of
the
product
by
connecting/
disconnecting
a
chemical
metering
pump
from
a
tote.
Chemicalspecific
exposure
data
were
not
submitted
to
support
the
pulp
and
paper
manufacturing.
Therefore,
AD
developed
a
screening­
level
assessment
using
surrogate
data
to
determine
the
potential
risks
associated
with
pulp
and
paper
manufacturing.
The
most
representative
data
available
for
connecting
a
chemical
metering
pump
to
a
tote
in
industrial
facilities
are
the
monitoring
data
from
the
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study
(
CMA).
The
liquid
pump
data
from
the
pulp
and
paper
preservative
loading
were
used
to
develop
this
screening­
level
assessment.
The
dermal
unit
exposure
(
UE)
of
0.00454
mg/
lb
a.
i.
for
the
liquid
pump
was
based
on
7
replicates
where
the
test
subjects
were
wearing
a
single
layer
of
clothing
and
chemical
resistant
gloves.
The
inhalation
UE
of
0.000265
mg/
lb
a.
i.
was
based
on
the
same
7
replicates.

The
dermal
MOE
for
the
liquid
pump
application
is
not
of
concern
because
it
is
65,000
which
is
greater
than
the
target
MOE
of
300.
In
addition,
the
inhalation
MOE
does
not
pose
a
concern,
because
it
is
120,000,
which
is
greater
than
the
inhalation
target
MOE
of
3,000.

°
For
metal
working
fluids
the
daily
amount
of
cutting
fluid
handled
used
in
this
Page
28
of
33
assessment
was
based
on
information
provided
in
EPA's
document
entitled
"
The
Use
of
Models
for
Estimating
Exposure
and
Risk
of
Antimicrobials
in
Metalworking
Fluids"
(
Dang,
1997).
This
handler
assessment
addresses
the
worker
pouring
the
preservative
into
the
metal
working
fluid
to
be
treated.
The
high
end
assumption
of
the
amount
of
cutting
fluid
handled
daily
was
300
gallons.
Therefore,
4.29
lbs
a.
i./
day
could
be
handled
by
workers
utilizing
open
pour
and
chemical
metering
pump
techniques
(
i.
e.,
300
gal
cutting
fluid
preserved/
day
x
0.3%
product
x
9.55
lb/
gal
x
50%
ai).
The
0.3%
application
rate
of
the
product
by
weight
of
the
material
treated
is
the
maximum
application
rate
allowed
for
metal
working
fluids.

The
potential
for
occupational
exposure
is
based
on
the
loading
of
the
product
by
open
pouring
or
connecting/
disconnecting
the
chemical
metering
pump.
Chemicalspecific
exposure
data
were
not
submitted
to
support
the
cutting
fluids
use.
Therefore,
AD
has
developed
a
screening­
level
assessment
using
surrogate
data
to
determine
the
potential
risks
associated
with
the
cutting
fluid/
oils
use.
The
most
representative
data
available
for
open
pouring
and
chemical
metering
pump
for
industrial
uses
are
the
monitoring
data
from
the
CMA
Antimicrobial
Exposure
Assessment
Study.
The
liquid
open
pour
and
liquid
pump
data
for
the
metal
fluid
loading
were
used
to
develop
the
screening­
level
assessment.
The
dermal
UE
of
0.184
mg/
lb
a.
i.
for
liquid
open
pour
is
based
on
8
replicates
with
the
test
subjects
wearing
a
single
layer
of
clothing
and
chemical
resistant
gloves
(
UEs
are
not
available
for
the
"
no
glove"
scenarios).
The
dermal
UE
of
0.312
mg/
lb
a.
i.
for
liquid
pump
is
based
on
only
2
replicates
with
the
test
subjects
wearing
a
single
layer
of
clothing
and
chemical
resistant
gloves
(
UEs
are
not
available
for
the
"
no
glove"
scenarios).
The
inhalation
UEs
are
based
on
the
same
replicates
specific
to
the
method
of
application,
as
previously
described.
The
inhalation
UE
for
open
pour
is
0.00854
mg/
lb
a.
i.
and
the
UE
for
liquid
pump
is
0.00348
mg/
lb
a.
i..

The
dermal
MOEs
for
both
methods
of
application,
liquid
pour
and
pump,
are
not
of
concern.
They
are
8,900
and
5,200
respectively.
Both
of
these
values
are
greater
than
the
target
MOE
for
ST/
IT
which
is
300.
In
addition,
the
inhalation
MOEs
for
both
methods
of
application
do
not
pose
a
concern.
They
are
20,000
(
pour)
and
50,000
(
pump),
both
of
which
are
greater
than
the
target
inhalation
MOE
of
3,000.

End
User
°
For
the
drilling
muds
and
flooding
fluids,
communication
between
AD
and
experts
in
the
industry
was
used
to
estimate
the
amount
of
a.
i.
handled
per
day
during
the
oil­
ell
activities.
Biocide
is
typically
added
directly
to
drilling
rig
mud
tanks
via
open
pouring.
Over
a
3­
6
week
period,
while
a
13,000
ft
well
is
being
drilled,
1
to
2
drums
(
1
drum
=
42
gallons)
of
biocide
may
be
used
if
microbiological
problems
are
encountered.
Therefore
the
short­
term
exposure
assessment
used
5.6
gallons
for
the
amount
of
biocide
handled
per
day
by
the
drilling
rig
worker
[
i.
e.,
(
2
drums
x
42
gal/
drum)/
5
days/
week
x
3
weeks)
=
5.6
gal/
day)].
The
intermediate
term
exposure
assessment
used
2.8
gallons
for
the
amount
of
biocide
handled
per
day
by
Page
29
of
33
the
drilling
rig
worker
[
i.
e.,
(
2
drums
x
42
gal/
drum)
/
(
5
days/
week
x
6
weeks)
=
2.8
gal/
day].
For
the
secondary
recovery
application,
the
biocide
is
meter
pumped
into
the
produced
water
before
it
is
reinjected
into
the
formation
ro
well.
Since
the
biocide
is
used
as
a
short
slug
treatment
(
not
a
continuous
treatment)
via
metering
pump
in
the
secondary
recovery
systems,
the
drilling
rig
worker
handling
the
biocide
via
open
pouring
is
expected
to
have
a
higher
exposure
than
the
secondary
recovery
worker.
Therefore
the
drilling
rig
worker
exposure
was
chosen
as
the
representative
high­
end
worker
for
all
the
oil
well
uses.
Based
on
these
use
estimates,
0.117
lb
a.
i./
day
(
ST)
and
0.0584
lb
a.
i./
day
(
IT)
could
be
handled
via
pouring
by
workers
(
i.
e.,
5.6
(
ST)
or
2.8
(
IT/
LT)
gal
product
handled/
day
x
8.34
lbs/
gal
(
assume
the
density
of
water)
x
50%
a.
i.
x
0.5%
product).

The
potential
for
occupational
exposure
is
based
on
the
loading
of
the
product
by
open
pouring
or
connecting/
disconnecting
the
chemical
metering
pump.
Chemicalspecific
exposure
data
were
not
submitted
to
support
the
materials
preservatives
use.
Therefore,
AD
has
developed
a
screening­
level
assessment
using
surrogate
data
to
determine
the
potential
risks
associated
with
the
materials
preservatives
uses.
The
most
representative
data
available
for
open
pouring
are
the
monitoring
data
from
the
CMA
Antimicrobial
Exposure
Assessment
Study.
The
liquid
open
pour
from
the
preservative
loading
are
used
to
develop
the
screening­
level
assessment.
The
dermal
UE
of
0.135
mg/
lb
a.
i.
for
liquid
open
pour
is
based
on
only
2
replicates
where
th
test
subjects
were
wearing
a
single
layer
of
clothing
and
chemical
resistant
gloves
(
UEs
are
not
available
for
the
"
no
glove"
scenario).
The
inhalation
UE
is
based
on
the
same
2
replicates
and
is
0.00346mg/
lb
a.
i
.
For
open
pour.
Although
this
explore
scenario
is
based
on
minimal
replicates,
the
exposure
values
are
similar
to
those
found
in
PHED
for
similar
scenarios.

The
liquid
pour
application
for
the
uses
sites
of
drilling
muds
and
flooding
fluids
were
both
assessed
with
the
same
values
because
the
application
rate
for
both
are
0.5%
product
(
0.25%
a.
i.)
by
weight
of
the
material
treated.
The
short
term
dermal
MOE
was
440,000
and
the
inhalation
MOE
was
1.8
x
10E6,
which
are
both
well
above
their
respective
target
MOEs.
The
intermediate
term
dermal
MOE
was
890,000
and
the
inhalationMOE
is
3.7
x
10E6,
which
again
are
well
above
the
target
MOEs
and
are
not
of
concern.

There
are
no
representative
unit
exposures
data
for
chemical
metering
(
i.
e.
liquid
pump)
into
secondary
recovery
oil
operations.
Since
the
volume
of
water
being
treated
in
secondary
recovery
operations
is
so
large,
the
available
CMA
data
con
not
be
reliably
extrapolated.
This
is
because
CMA
data
are
based
on
activities
that
handle
much
lower
volumes
and
possibly
different
techniques.
Therefore,
it
was
assumed
that
if
the
open
pour
handling
activities
for
the
other
oil
well
operations
resulted
in
MOEs
that
are
not
of
concern
(
in
this
assessment,
the
MOEs
are
not
of
concern),
then
the
MOEs
for
the
closed
system
chemical
metering
into
secondary
recovery
operations
would
also
not
be
of
concern.
AD
requests
that
confirmatory
data
(
monitoring
unit
exposure
data)
be
conducted
to
show
that
this
assumption
is
accurate.
Page
30
of
33
6.2
Occupational
Postapplication
Exposure
6.2.1
Occupational
Workers:

Occupational
painter
post­
application
exposures
result
when
bystanders
contact
areas
in
which
the
antimicrobial
end­
use
product
has
been
recently
applied.
For
azadioaxabicyclooctane,
these
exposures
are
expected
to
be
minimal.

6.2.2
Metalworking
Fluids,
Machinist:

There
is
a
potential
for
dermal
and
inhalation
exposure
when
a
worker
handles
treated
metalworking
fluids.
This
route
of
exposure
occurs
after
the
chemical
has
been
incorporated
into
the
metal
working
fluid
and
a
machinist
is
using/
handling
this
treated
end­
product.
The
exposure
is
assessed
and
the
MOEs
are
in
Table
6.3,
with
explanations
and
the
appropriate
equations.
A
screening­
level
long­
term
dermal
exposure
estimate
was
derived
through
using
the
2­
hand
imersion
model
from
ChemSTEER.
The
model
is
available
at
www.
epa.
gov/
opptintr/
exposure/
docs/
chemsteer.
htm.
The
2­
hand
immersion
model
is
as
follows:

Dermal
Dose
=
840cm2(
hand
surface
area)
x
%
a.
i.
x
10.3
mg/
cm2
(
film
thickness)
x
1
frequency/
day
Body
weight
(
kg)

The
value
of
the
film
thickness,
10.3
mg/
cm2
is
from
the
document
titled,
"
A
Laboratory
Method
to
Determine
the
Retention
of
Liquids
on
the
Surface
of
Hands."
A
screening­
level
long­
term
inhalation
exposure
estimate
for
treated
metal
working
fluids
has
been
developed
using
the
OSHA
PEL
for
oil
mist,
and
the
high­
end
oil
mist
concentration
is
based
on
the
OSHA's
Permissible
Exposure
Limit
(
PEL)
of
5
mg/
m3
(
NIOSH,
1998).
The
equation
used
for
calculating
the
inhalation
dose
is:

Inhalation
Dose
=
5
mg/
m3
x
1.25
m3
/
hr
x
%
a.
i.
x
8
hours/
day
70
kg
Table
6.3:
MOEs
for
Long
Term
Machinist
Post
Application
Exposure
to
Azadioxabicyclooctane
Treated
MWF
Substrate
Treated/
Handled
through
Exposure
Scenario
Application
Rate
(%
a.
i.
by
weight
of
material
treated)
a
Daily
Dose
(
mg
a.
i./
kg
per
day)
b
Long
Term
MOE
c
Dermal
Dosed
Inhalation
Dosee
Dermal
(
Target
=
1,000)
Inhalation
(
Target
=
3,000)

Metalworking
cutting
fluids
0.15
0.1854
0.00107
540
9,900
0.05
0.0618
0.000357
1,600
30,000
a:
The
maximum
application
rate
of
0.3%
product
(
0.15%
a.
i).
by
weight
of
material
treated
generates
an
MOE
of
concern,
whereas
using
materials
treated
at
the
minimum
application
rates
specified
in
the
table
(
0.1%
product,
0.05%
a.
i.),
an
MOE
that
Page
31
of
33
is
not
of
concern
is
generated.
b:
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Unit
Exposure
(
mg/
lb
a.
i.)
x
rate
x
amount
handled
x
(
1/
body
weight
(
kg))
c:
MOE
=
Toxicity
Endpoint
(
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day);
where
dermal
NOAEL
=
100
mg/
kg/
day
and
the
inhalation
LOAEL
=
10.6
mg/
kg/
day
d:
Dermal
Dose
=
840cm2(
hand
surface
area)
x
%
a.
i.
x
10.3
mg/
cm2
(
film
thickness)
x
1
frequency/
day
Body
weight
(
kg)
The
factor
of
10.3
mg/
cm2
is
representative
of
the
film
thickness,
assuming
that
the
worker
is
exposed
to
the
fluid
through
a
complete
double
dip
in
which
both
hands
are
immersed,
and
the
toxicology
claims
the
chemical
to
be
a
dermal
irritant
(
September
0992).
In
addition,
it
is
assumed
that
the
body
weight
is
70
kg,
and
the
worker
works
8
hrs/
day
for
five
out
of
seven
days
per
week.

e:
Inhalation
Dose
=
5
mg/
m3
x
1.25
m3
/
hr
x
%
a.
i.
x
8
hours/
day
70
kg
The
Agency
conducted
the
screening
level
assessment
using
the
Chemical
Engineering
Branch
(
CEB)
model
(
U.
S.
EPA,
1991).
Exposure
assumptions
used
in
the
model
are
presented
in
Dang,
1997.
The
CEB
model
uses
measured
and/
or
assumed
airborne
oil
mist
concentrations
for
metal
working
operations.
Since
no
measured
concentrations
are
available
for
azadioxabicyclooctane,
the
high­
end
oil
mist
concentration
is
based
on
the
OSHA's
Permissible
Exposure
Limit
(
PEL)
of
5
mg/
m3
(
NIOSH,
1998).
The
inhalation
rate
for
adults
is
1.25
m3
/
hr;
the
exposure
duration
is
8
hours
per
day;
and
body
weight
is
70
kg.

At
the
maximum
application
rate
(
0.3%
product
by
weight
of
material
to
be
treated,
0.15%
a.
i.)
on
the
label
(
1529­
28),
there
is
concern
with
the
dermal
exposure
to
the
worker.
The
target
dermal
MOE
for
LT
exposure
is
1,000,
and
at
the
maximum
rate,
the
MOE
is
540.
However,
when
the
worker
comes
into
contact
with
fluid
that
has
been
treated
at
the
minimum
application
rate
(
0.1%
product
by
weight
of
material
to
be
treated,
0.05%
a.
i.),
the
MOE
is
1,600
which
is
not
of
concern
since
it
is
greater
than
1,000.
Post
application
exposure
to
MWF
will
not
present
any
dermal
concern
if
the
fluid
the
worker
is
exposed
to
has
been
treated
at
the
rate
of
0.1%
product
by
weight
of
MWF
treated.
The
calculated
inhalation
MOEs
for
both
application
rates
were
well
over
the
target
inhalation
MOE
of
3,000.
They
were
9,900
(
maximum
application
rate),
and
30,000
(
minimum
application
rate).
These
indicate
that
the
inhalation
risks
do
not
exceed
the
Agency's
level
of
concern
for
machinist
exposures
to
metal
working
fluid.

6.3
Data
Limitations/
Uncertainties
Currently,
azadioxabicyclooctane
chemical­
specific
handler
or
postapplication
exposure
studies
that
meet
Agency
guidelines
have
not
been
identified.
Surrogate
dermal
and
inhalation
data
from
Chemical
Manufacturers
Association
(
CMA)
and
PHED
databases
were
used
to
assess
handler
exposure.
Typically
CMA
and
PHED
databases
are
based
on
central
tendency
estimates.
PHED
is
based
on
the
geometric
mean
unit
exposures
and
CMA
is
based
on
the
arithmetic
mean
exposures.
Note
that
CMA
surrogate
data
have
the
following
deficiencies:

C
The
inhalation
concentrations
were
typically
below
the
detection
limits,
and
the
unit
exposures
for
the
inhalation
exposure
route
could
not
be
accurately
calculated.

C
The
CMA
Unit
exposure
data
was
used
for
each
of
the
worker
scenarios
assessed.
These
data
are
of
poor
quality
because
they
are
based
on
limited
number
of
replicates
(
i.
e.,
2)
which
does
not
meet
the
Agency's
standard
of
15.
AD
requests
that
exposure
confirmatory
data
be
collected
to
show
that
the
exposures
assessed
in
this
memo
using
the
CMA
data
are
valid.
Page
32
of
33
C
There
are
no
representative
unit
exposures
data
for
chemical
metering
into
secondary
recovery
oil
operations.
Since
the
volume
of
water
being
treated
in
secondary
recovery
operations
is
so
large,
the
available
CMA
Data
con
not
be
reliably
extrapolated
because
they
are
based
on
activities
that
handle
much
lower
volumes
and
possibly
different
techniques.
Therefore,
ti
was
assumed
that
if
the
open
pour
handling
activities
for
the
other
oil
well
operations
resulted
in
MOEs
that
are
not
of
concern,
then
the
MOEs
for
the
close
system
chemical
metering
into
secondary
recovery
operations
would
also
not
be
of
concern.
AD
requests
that
confirmatory
data
be
conducted
to
show
that
this
is
accurate.

The
following
factors
concerning
PHED
and
the
residential
SOPs
should
also
be
noted:

C
The
job
functions
where
pesticides
are
commonly
used
may
be
different
from
those
job
functions
where
antimicrobial
chemicals
are
used
(
i.
e.,
representativeness
issue).

C
The
basic
assumption
underlying
the
PHED
database
is
that
exposure
to
pesticide
handlers
is
primarily
a
function
of
the
physical
parameters
associated
with
handling
and
applying
of
the
product
rather
than
the
chemical
properties
of
the
individual
active
ingredients.
Therefore,
it
is
important
to
recognize
the
potential
effects
the
chemical
properties
of
azadioxabicyclooctane
may
have
on
the
exposure
rates.

°
No
information
regarding
the
amount
of
end
use
product
handled
daily
was
provided
by
the
registrant.
The
AD
SOP
was
used
for
developing
a
value
to
use
in
this
assessment.

°
Any
changes
to
the
toxicological
endpoints
will
need
to
be
incorporated
into
this
review
Page
33
of
33
7.0
REFERENCES
Antimicrobials
Division
Standard
Operating
Procedure.
Summary
of
Antimicrobial
Standard
Operating
Procedure
(
SOP)
Assumptions
for
Residential
and
Occupational
Exposure
Assessments,
January
2005.

Chemical
Engineering
Branch:
Economics,
Exposure,
and
Technology
Division.
"
Options
for
Revising
CEB's
Model
for
Screening
Level
Estimates
of
Dermal
Exposure."
June
2000.

Cinalli,
Christina,
et
al.
A
Laboratory
Method
to
Determine
the
Retention
of
Liquids
on
the
Surface
of
Hands.
Exposure
Evaluation
Division.
September
1992.

Dang,
W.
1997.
"
The
Use
of
Models
for
Estimating
Exposure
and
Risk
of
Antimicrobials
in
Metalworking
Fluids"

PHED
Surrogate
Exposure
Guide.
1997.
Estimates
of
Worker
Exposure
from
the
Pesticide
Handler
Exposure
Database
Version
1.1.
May
1997.

U.
S.
EPA.
1999.
Evaluation
of
the
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study
(
Amended
on
December
8,
1992).
Memorandum
from
Siroos
Mostaghimi,
Ph.
D.,
Environmental
Engineer
to
Julie
Fairfax,
PM
#
36.
November
4,
1999.

U.
S.
EPA
Residential
Standard
Operating
Procedures.
1997
&
2001.
