Document ID: EPA-HQ-OPP-2005-0200-0016
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-22T05:00Z

Human
Exposure
Assessment
for
a
Reregistration
Submission
for
1,2­
Benzisothiazolin­
3­
one
(
BIT)

Antimicrobials
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
1921
Jefferson
Davis
Highway
Arlington,
VA
22202
September
1,
2005
2
EXECUTIVE
SUMMARY
1,2­
Benzisothiazolin­
3­
one
(
BIT)
is
an
industrial
preservative
that
is
recommended
to
control
the
growth
of
microorganisms
in
the
preserved
product.
BIT
is
recommended
for
use
as
an
industrial
preservative
for
the
protection
of
water­
based
adhesives,
caulks,
sealants,
grouts,
spackling,
readymixed
cements,
ready­
mixed
wallboard
compounds,
aqueous
compositions
such
as
emulsion
paints,
aqueous
slurries,
home
cleaning
and
car
care
products,
inks,
photographic
processing
solutions,
paints
and
stains,
titanium
dioxide
slurries,
oil
in
water
emulsions,
latices,
gas/
oil
drilling
fluids,
metalworking
fluids,
casein/
rosin
dispersions,
textile
spin­
finish
solutions,
laundry
detergent,
pesticide
formulations,
tape
joint
compound,
leather
processing
solutions,
and
for
preservation
of
fresh
animal
hides
and
skins.

The
application
rates
used
in
this
assessment
are
intended
to
reflect
the
upper
range
of
the
labeled
rates.
A
wide
range
of
registered
labels
(
approximately
33)
were
available
for
review.
Table
4
presents
the
conversion
the
maximum
labeled
rates
to
pounds
of
active
ingredient
(
ai)
handled.

The
Occupational
and
Residential
Exposure
Chapter
of
the
BIT
Reregistration
Eligibility
Decision
Document
(
RED)
addresses
potential
exposures
and
risks
to
humans
who
may
be
exposed
to
BIT
in
"
occupational
settings"
and
the
general
population
in
"
residential
settings."
This
occupational
and
residential
exposure
assessment
provides
estimates
of
exposures
and
risks
to:
(
1)
handlers
(
mixers,
loaders,
applicators)
of
BIT
products;
and
(
2)
individuals
who
are
involved
in
postapplication
activities
or
occupy
areas
where
BIT­
containing
products
have
been
recently
applied.

Toxicity
endpoints
for
dermal,
inhalation
and
incidental
ingestion
for
all
time
periods
are
extrapolated
from
the
systemic
subchronic
oral
NOAEL
of
5
mg/
kg/
day
based
on
emesis
and
clinical
chemistry
alterations
of
both
male
and
female
dogs
at
the
LOAEL
of
20
mg/
kg/
day.
The
Revised
Report
of
the
Antimicrobials
Division's
Toxicology
Endpoint
Selection
Committee
(
ADTC),
dated
April
22,
2005,
recommended
the
use
of
the
selected
oral
endpoints
for
the
dermal
and
oral
routes
of
exposure,
assuming
100
percent
absorption
by
the
inhalation
route
and
41
percent
by
the
dermal
route.

An
uncertainty
factor
or
"
target"
margin
of
exposure
(
MOE)
of
100
is
based
on
10x
for
differences
among
humans
(
intra
species
variability)
and
10x
for
differences
between
the
test
animals
and
humans
(
inter
species
extrapolation)
for
dermal
endpoints.
Thus
MOEs
of
greater
than
100
do
not
exceed
the
Agency's
level
of
concern
for
dermal
occupational
or
residential
uses
(
all
exposure
durations).
The
target
MOE
for
incidental
short­
and
intermediate­
term
exposures
is
300.
For
inhalation
exposures
the
target
MOE
is
100
for
all
durations.
However,
an
additional
10x
uncertainty
factor
for
inhalation
is
needed
to
account
for
the
route­
to­
route
extrapolation
from
an
oral
endpoint
to
determine
if
a
repeat
inhalation
toxicity
study
is
warranted
(
Note:
Inhalation
toxicity
study
is
not
warranted).
This
chemical
was
classified
as
Group
D
carcinogen,
meaning
it
is
not
classifiable
as
to
human
carcinogenicity.
Group
D
is
used
for
agents
with
inadequate
human
and
animal
evidence
of
carcinogenicity
or
for
which
data
are
not
available.
3
At
present,
the
Agency
does
not
have
available
chemical­
specific
residential
and
occupational
handler
or
postapplication
exposure
studies
for
BIT.
Therefore,
exposures
were
estimated
using
surrogate
data
from
Chemical
Manufacturers
Association
(
CMA);
surrogate
data
from
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1;
U.
S.
EPA's
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs);
application
rates
from
EPA­
registered
product
labels;
EPA
estimates
of
daily
amounts
of
product
handled;
and
ChemSTEER
model
for
metal
working
fluids.
The
exposure
scenarios
risks
are
summarized
as
outlined
below.

Occupational
Handlers.
In
order
to
estimate
handler
exposures,
PHED
data
were
used
to
evaluate
paint
brush
and
airless
sprayer
painting
scenarios
while,
CMA
data
were
used
to
evaluate
occupational
handlers
involved
in
mixing/
loading
liquids
for
general
preservatives
used
in
industrial
processes
and
water
systems
and
metalworking
fluids.
The
exposure
and
risk
assessments
for
occupational
handlers
were
conducted
using
product
label
application
rates,
use
information,
CMA
and
PHED
unit­
exposure
data,
and
the
ChemSTEER
model.
The
dermal
MOEs
were
greater
than
100
(
commercial
painting
MOE
=
90
for
airless
sprayer)
and
the
inhalation
MOEs
were
greater
than
1,000;
therefore,
they
do
not
exceed
the
Agency's
level
of
concern.
For
each
job
function,
the
total
MOE
was
used
to
present
total
risk
resulting
from
dermal
and
inhalation
exposures.
All
total
MOEs
for
BIT
are
greater
than
100,
except
for
commercial
use
of
the
airless
sprayer
(
total
MOE
=
85).

Residential
Handlers.
The
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs)
(
U.
S.
EPA,
1997a)
were
used
to
estimate
exposures
for
residential
handler
scenarios.
The
residential
handler
scenarios
are
similar
to
those
developed
for
occupational
handlers;
only
the
amounts
handled
and
clothing/
glove
scenarios
are
somewhat
different.
MOEs
were
greater
than
100
for
dermal
and
100/
1,000
for
inhalation
exposures
in
all
of
the
scenarios
listed.
For
each
job
function,
the
total
MOE
was
used
to
present
total
risk
resulting
from
dermal
and
inhalation
exposures.
All
total
MOEs
for
BIT
are
greater
than
100,
and
therefore,
not
of
concern.

Occupational
Postapplication
Exposure.
Postapplication
inhalation
exposures
may
occur
in
the
industrial
settings
around
the
water
systems
via
inhalation,
and
dermal
exposures
may
occur
while
maintaining
industrial
equipment.
However,
occupational
postapplication
dermal
and
inhalation
exposures
to
BIT
are
likely
to
be
minimal
compared
to
handler
exposure
because
of
dilution
during
processing.
No
postapplication
exposure
data
have
been
submitted
to
the
agency
to
determine
the
extent
of
postapplication
exposures
in
the
industrial
settings.
Inhalation
exposures
are
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
BIT
is
low.

Residential
Postapplication
Exposure.
Residential
exposures
result
when
children
contact
areas
in
which
the
pesticide
end­
use
product
has
been
recently
applied.
The
residential
postapplication
scenario
considered
representative
of
high
end
exposure
in
this
assessment
is
based
on
toddler
exposure
to
residues
from
hard
surfaces
(
i.
e.,
floors)
that
have
been
mopped
with
a
product
containing
BIT.
The
toddler
dermal
MOE
was
above
the
target
of
100
and
incidental
oral
MOEs
were
above
the
target
of
300,
and
therefore,
are
not
of
concern.
The
Aggregate
Risk
Index
(
ARI)
method
was
used
to
present
the
total
risk
(
incidental
oral
+
dermal
exposure)
because
the
target
4
MOEs
were
different
for
the
dermal
and
incidental
oral
routes.
ARIs
greater
than
1.0
do
not
exceed
the
Agency's
level
of
concern.
The
ARI
for
children
playing
on
a
BIT­
treated
floor
is
48,
and
therefore,
not
of
concern.

BIT
labels
also
include
a
microbiocide
use
in
laundry
detergents,
fabric
softeners,
and
stain
removers.
The
incidental
oral
MOE
as
a
result
of
mouthing
treated
fabric
is
1,700
and
is
not
of
concern.
The
dermal
MOEs
calculated
for
both
toddler
and
adult
scenarios
are
also
not
of
concern
(
MOEs
=
7,200
and
11,000
for
toddlers
and
adults,
respectively).
Finally,
t
he
ARI
is
5.2,
and
therefore,
not
of
concern
(
i.
e.,
an
ARI
greater
than
1
is
not
of
concern).

Data
Gaps,
Uncertainties,
and
Limitations
Chemical­
specific
data
are
not
available
to
assess
exposure
for
BIT.
At
present,
surrogate
data
are
the
only
option
to
assess
postapplication
exposures
for
BIT.
Specific
data
gaps
and
limitations
with
the
surrogate
data
and
the
assumptions
are
presented
in
Section
4.0.
5
1.0
BACKGROUND
Purpose
This
document,
which
is
for
use
in
EPA's
development
of
the
1,2­
Benzisothiazolin­
3­
one
(
BIT)
Reregistration
Eligibility
Decision
Document
(
RED),
presents
EPA's
results
of
its
review
of
the
potential
human
health
effects
of
occupational
and
residential
exposure
to
BIT.

Criteria
for
Conducting
Exposure
Assessments
An
occupational
and/
or
residential
exposure
risk
assessment
is
required
for
an
active
ingredient
if
(
1)
certain
toxicological
criteria
are
triggered
and
(
2)
there
is
potential
exposure
to
handlers
(
mixers,
loaders,
applicators,
etc.)
during
use
or
to
persons
entering
treated
sites
after
application
is
complete.
For
BIT,
both
criterion
are
met.

1.1
Summary
of
Toxicity
Concerns
Relating
to
Occupational
Exposures
Acute
Toxicology
Categories
Table
1
presents
the
acute
toxicity
categories
as
outlined
in
the
1,2­
Benzisothiazolin­
3­
one
­
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
dated
September
25,
2002.

Table
1.
Acute
Toxicity
Categories
for
BIT
Guideline
No.
Study
Type
MRID#(
s)
Results
Toxicity
Category
870.
1100
Acute
Oral
Toxicity
41022101
42858101
LD50
=
670
mg/
kg
(
M)

LD50
=
784
mg/
kg
(
F)
III
870.
1200
Acute
Dermal
Toxicity
41022102
42858102
LD50>
2000
mg/
kg
III
81­
3
Acute
Inhalation
Toxicity
waiver
granted
81­
4
Primary
Eye
Irritation
42905102
severe
eye
irritant
I
81­
5
Primary
Skin
Irritation
42905101
slight
irritant
IV
81­
6
Dermal
Sensitization
41750001
42858103
moderate
dermal
sensitizer
­
6
Summary
of
Toxicological
Endpoint
Selection
The
1,2­
Benzisothiazolin­
3­
one
­
Revised
Report
of
the
Antimicrobials
Division's
Toxicology
Endpoint
Selection
Committee
(
ADTC),
dated
April
22,
2005,
indicates
that
there
are
toxicological
endpoints
of
concern
for
BIT
(
USEPA
2005).
The
endpoints,
and
associated
uncertainty
factors,
used
in
assessing
the
risks
for
1,2­
Benzisothiazolin­
3­
one
are
presented
in
Table
2.

Table
2.
Toxicological
Endpoints
for
Assessing
Occupational
and
Residential
Exposures/
Risks
Exposure
Scenario
Dose
Used
In
Risk
Assessment
(
mg/
kg/
day)
Target
MOE
or
UF
Study
and
Toxicological
Effects
Dietary
Risk
Assessments
Incidental
Oral
(
Short­
and
intermediate
­
term
NOAEL
=
5
UF
=
300
(
10x
interspecies
extrapolation,
10x
intra­
species
variation,
FQPA
SF
of
1,
and
data
base
UF
of
3x)

Acute
RfD
=
0.017
mg/
kg/
day
Co­
Critical
studies:

Subchronic
toxicity
,
dog
,
NOAEL
=
5
mg/
kg/
day
based
on
increased
incidence
of
emesis
and
clinical
chemistry
alterations
at
20
mg/
kg/
day.

and
Subchronic
toxicity
,
rats
,
NOAEL
=
8.42
mg/
kg/
day
based
on
macroscopic
and
microscopic
lesions
in
the
nonglandular
and
glandular
regions
of
the
stomach
Non­
Dietary
Risk
Assessments
Dermal
All
Time
Periods
(
occupational
and
residential)
NOAEL
=
5a
MOE
=
100
(
10x
inter­
species
extrapolation,
10x
intra­
species
variation)
Co­
Critical
studies:

Subchronic
toxicity
,
dog
,
NOAEL
=
5
mg/
kg/
day
based
on
increased
incidence
of
emesis
and
clinical
chemistry
alterations
at
20
mg/
kg/
day.

and
Subchronic
toxicity
,
rats
,
NOAEL
=
8.42
mg/
kg/
day
based
on
macroscopic
and
microscopic
lesions
in
the
nonglandular
and
glandular
regions
of
the
stomach
Inhalation
All
Time
Periods
(
occupational
and
residential)
NOAEL
=
5
MOE
=
100
(
10x
inter­
species
extrapolation,
10x
intra­
species
variation)

An
additional
10x
route­
to­
route
extrapolation
is
used
to
determine
if
an
inhalation
toxicity
study
is
warranted.

Cancer
No
cancer
data
available
for
1,2­
benzisothiaolzin­
3­
one
a
The
dermal
absorption
is
41
percent.
7
1.2
Summary
of
Use
Pattern
and
Formulations
Type
of
Pesticide/
Targeted
Pest/
Use
Sites
BIT
is
used
as
a
material
preservatives
in
several
types
occupational
and
residential
products.
BIT
is
an
industrial
preservative
that
is
recommended
to
control
the
growth
of
microorganisms
in
the
preserved
product.
BIT
is
recommended
for
use
as
an
industrial
preservative
for
the
protection
of
water­
based
adhesives,
caulks,
sealants,
grouts,
spackling,
ready­
mixed
cements,
ready­
mixed
wallboard
compounds,
aqueous
compositions
such
as
emulsion
paints,
aqueous
slurries,
home
cleaning
and
car
care
products,
inks,
photographic
processing
solutions,
paints
and
stains,
titanium
dioxide
slurries,
oil
in
water
emulsions,
latices,
gas/
oil
drilling
fluids,
metalworking
fluids,
casein/
rosin
dispersions,
textile
spin­
finish
solutions,
laundry
detergent,
pesticide
formulations,
tape
joint
compound,
leather
processing
solutions,
and
for
preservation
of
fresh
animal
hides
and
skins.

Formulation
Types
and
Percent
Active
Ingredient
BIT
is
a
water
soluble,
liquid
organic
biocide
(
also
called
an
antimicrobial
or
in­
can
preservative).
BIT
is
formulated
as
a
soluble
liquid
and
is
available
in
formulations
containing
between
0.9
percent
to
84
percent
active
ingredient.

1.3
Method
and
Types
of
Equipment
Used
for
Mixing/
Loading/
Applying
The
Agency
determines
potential
exposures
to
pesticides
handlers
by
identifying
exposure
scenarios
from
the
various
application
equipment­
types
that
are
plausible,
given
the
label
uses.
The
occupational
and
residential
use
patterns
of
BIT
are
identified
in
Table
3.
The
exposure
scenarios
1­
5
are
based
on
CMA
data
and
scenarios
6­
7
are
based
on
PHED
data.

Table
3.
Exposure
Scenarios
for
Occupational
and
Residential
Handlers
Exposure
Scenarios
Use
Site
Category
Scenario
Descriptions
Data
Source
Liquid
Pour
for
Preservatives
Material
Preservatives
Scenario
involves
adding
an
in­
can
preservative
to
paints,
adhesives,
slurries,
oil/
gas
drilling
fluids,
etc.
Exposure
occurs
when
pouring
the
biocide
into
the
slurry.
CMA
gloved
data
for
liquid
pour
of
preservatives
are
used
(
U.
S.
EPA
1999).
*

Liquid
Pump
for
Preservatives
Material
Preservatives
For
large
oil/
gas
drilling
fluid
secondary
recovery
operations
the
preservative
is
added
via
a
closed
loading
system
CMA
gloved
data
for
liquid
pump
preservatives
are
used
(
U.
S.
EPA
1999).*

Liquid
Pour
for
Metal
Working
Fluids
Material
Preservatives
Exposure
occurs
either
via
loading
and
filling
bulk
tanks
or
machine
sumps,
direct
dermal
or
inhalation
contact
of
cutting
oils,
or
setup/
maintenance
of
the
automatic
metering
systems.
CMA
gloved
data
for
liquid
pour
and
pump
of
metalworking
fluids
are
used
(
U.
S.
EPA
1999).*
Table
3.
Exposure
Scenarios
for
Occupational
and
Residential
Handlers
Exposure
Scenarios
Use
Site
Category
Scenario
Descriptions
Data
Source
8
Daily
Dermal
Exposure
Dermal
Unit
Exposure
mg
ai
lb
ai
x
Use
Rate
lb
ai
=
 

 
 
 

 
 

(
)
Wiping
for
Disinfectants
Material
Preservatives
Janitorial
&
residential
use
of
cleaning
products
containing
BIT.
CMA
ungloved
data
for
wiping
are
used
(
U.
S.
EPA
1999).

Mopping
for
Disinfectants
Material
Preservatives
Janitorial
and
residential
use
of
cleaning
products
containing
BIT.
CMA
ungloved
data
for
mopping
are
used
(
U.
S.
EPA
1999).

Painting
(
brush/
roller)
Material
Preservatives
Scenario
involves
painting
with
a
paint
brush
(
representative
of
painting
with
a
roller).
PHED,
1997
for
painting
Commercial
painters
based
on
long
pants,
long
sleeved
shirts,
and
no
gloves
Residential
painters
based
on
short­
pants,
short­
sleeved
shirts,
and
no
gloves
Airless
Painting
Material
Preservatives
Scenario
involves
painting
with
an
airless
sprayer.
PHED,
1997
for
airless
spraying
Commercial
painters
based
on
long
pants,
long
sleeved
shirts,
and
no
gloves
Residential
painters
based
on
short­
pants,
short­
sleeved
shirts,
and
no
gloves
*
Pump
liquid
is
not
assessed
because
target
MOE
for
pouring
is
not
exceeded.

2.0
Handler
Exposures
AD
assessed
the
risks
to
the
occupational
and
residential
handlers
using
the
dermal
and
inhalation
exposure
data
for
loading
liquid
formulations
using
the
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
(
DP
Barcode:
D247642)
and
PHED
Handlers
Exposure
Database
(
PHED
V1.1).
Table
3
also
presents
the
exposure
scenarios
for
occupational/
residential
handlers
presenting
the
AD
use
site
category
and
the
associated
data
source
used
to
develop
the
exposure
dose.
These
exposure
scenarios
were
used
to
assess
the
handler
risks
to
BIT's
antimicrobial
uses.

Potential
daily
inhalation
and
dermal
exposures
were
calculated
using
the
following
formulae:
9
ARI
IncidentalOralT
etMOE
OralMOE
DermalT
etMOE
DermalMOE
=
 

 
 
 

 
 

+
 

 
 
 

 
 
1
arg
arg
Daily
Inhalation
Exposure
InhalationUnit
Exposure
mg
ai
lb
ai
x
Use
Rate
lb
ai
=
 

 
 
 

 
 

(
)

The
potential
daily
inhalation
and
dermal
exposures
to
BIT
for
handlers
were
used
to
calculate
the
potential
doses
by
dividing
by
the
body
weight
of
70
kg.
The
Margin
of
Exposure
(
MOE)
was
calculated
by
dividing
the
NOAEL
by
the
inhalation
or
dermal
daily
dose
using
the
following
formula:

MOE
NOAEL
mg
kg
day
Daily
Dose
mg
kg
day
=
(
/
/
)

(
/
/
)

Since
the
dermal
and
inhalation
toxicological
endpoints
have
the
same
effect,
the
total
risk
from
both
routes
of
exposure
must
be
evaluated.
The
total
risk
(
inhalation
dose
+
dermal
dose)
was
evaluated
for
the
handler
scenarios
using
the
"
total"
MOE
approach
because
the
uncertainty
factors
are
the
same.
The
incidental
oral
route
and
dermal
route
for
children
are
also
based
on
the
same
effect,
however,
the
incidental
oral
route
has
an
additional
3x
data
base
uncertainty
factor.
Therefore,
the
Aggregate
Risk
Index
(
ARI)
method
was
used
because
the
target
MOEs
were
different
for
the
dermal
and
oral
routes.
ARIs
greater
than
1.0
do
not
exceed
the
Agency's
level
of
concern.
ARIs
were
calculated
using
the
following
formula:

The
assumptions
used
for
calculating
the
exposures
and
risks
in
this
assessment
are
provided
in
Table
4.
The
results
of
the
MOE
and
ARI
analyses
are
presented
in
Table
5.
All
inhalation
and
dermal
MOEs
were
greater
than100,
respectively,
and
do
not
exceed
the
Agency's
level
of
concern
for
occupational
and
residential
uses
(
Note:
commercial
painting
with
an
airless
sprayer
has
a
dermal
MOE
of
90).
For
each
job
function,
the
total
MOE
was
used
to
estimate
total
risk
resulting
from
dermal
and
inhalation
exposures.
All
of
the
scenarios
indicate
no
risks
of
concern
(
Note:
commercial
painting
with
an
airless
sprayer
where
the
total
MOE
=
85).
10
Table
4.
Exposure
Estimates/
Assumption
for
the
Daily
Amount
of
Preservative
Handled
Exposure
Scenarios
Use
Site
Category
Pounds
Active
Ingredient
(
ai)
Used
Liquid
Pour
for
Preservatives
Material
Preservatives
This
use
category
includes
industrial
process
intermediate
materials
(
dispersions,
slurries,
emulsions,
solutions,
etc.)
and
resulting
products
including
paints,
coatings,
adhesives,
textiles,
paper,
etc.
The
Agency
typically
assumes
10,000
lb
of
slurry
are
treated
per
day.
EPA
Reg
67071­
24
indicates
that
1­
5
lb
(
10%
ai)
of
material
preservative
are
used
per
1,000
lbs
of
slurry.
The
maximum
amount
of
active
ingredient
handled
is
5
lb
ai.
Equation
is
as
follows:
5
lb/
1,000
lb
slurry
x
10,000
lb
slurry
x
10%
ai=
5
lb
ai.

Industrial
Processes
and
Water
Systems
This
use
category
includes
industrial
process
water
from
leather
and
photo
processing
uses.
The
Agency
typically
assumes
10,000
lb
of
slurry
are
treated
per
day.
EPA
Reg
67071­
22
indicates
that
0.25­
2
lb
(
20%
ai)
of
product
are
used
per
1,000
lb
of
slurry.
The
maximum
amount
of
active
ingredient
handled
is
4
lb
ai.
Equation
is
as
follows:
2
lb/
1,000
lb
slurry
x
10,000
lb
slurry
x
20%
ai
=
4
lb
ai.

Oil/
gas
Drilling
Fluids
Biocides
are
typically
added
directly
to
drilling
rig
mud
tanks
via
open
pouring.
Over
a
3
to
6
week
period
a
13,000
ft
well
will
require
1
to
2
drums
(
1
drum
=
42
gallons)
of
biocide
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].
Note:
A
separate
intermediate­
term
assessment
was
not
performed
because
the
endpoint
is
the
same
for
all
durations
and
the
exposures
are
expected
to
be
less
because
the
amount
handled
would
be
less
than
the
high­
end
assumed
for
short­
term.

Since
the
amount
handled
are
in
terms
of
gallons,
it
is
necessary
to
convert
these
values
into
terms
of
pounds
by
using
water
density
of
8.34
lb/
gal.
Thus,
for
the
water­
based
drilling
fluid
scenario,
the
amount
of
biocide
handled
per
day
is
46.7
lbs
(
where
5.6
gal
x
8.34
lb/
gal)
for
the
short­
term
duration.
EPA
Reg
67071­
23
indicates
the
20%
ai
product
be
applied
at
0.05
to
0.15
percent
per
1000
lbs
treated.
The
maximum
amount
of
active
ingredient
handled
is
0.014
lb
ai.
Equation
is
as
follows:
0.15%
product
x
20%
ai
x
46.7
lbs
=
0.014
lb
ai.

Liquid
Pump
for
Preservatives
Oil/
gas
Drilling
Fluids,
Secondary
Recovery
For
large
secondary
recovery
operations
the
amount
of
produced
water
treated
via
metering
pump
can
exceed
420,000
gallons/
day.
For
the
secondary
recovery
scenario,
the
amount
of
water
treated
per
day
is
3,502,800
lbs
(
where
3,502,800
lbs
=
420,000
gal
x
8.34
lb/
gal).
The
maximum
amount
of
active
ingredient
handled
is
1050
lb
ai.
Equation
is
as
follows:
0.15%
product
x
20%
ai
x
3,502,800
lbs
=
1050
lb
ai.

Liquid
Pour
for
Metal
Fluids
Material
Preservatives
This
use
category
includes
metal
working
fluids.
The
Agency
typically
assumes
300
gallons
(
where
density
is
assumed
to
be
8.3
lb/
gal;
2,490
lb)
of
metalworking
fluids
are
use
per
day.
EPA
Reg
49403­
26
indicates
that
treated
metalworking
fluid
should
consist
of
0.08­
0.36%
of
the
formulated
preservative
(
9%
ai).
The
maximum
amount
of
ingredient
handled
is
0.81
lb
ai.
Equation
is
as
follows:
2,490
lb
metal
working
fluid
x
0.36%
preservative
x
9%
ai
=
0.81
lb
ai.
Table
4.
Exposure
Estimates/
Assumption
for
the
Daily
Amount
of
Preservative
Handled
Exposure
Scenarios
Use
Site
Category
Pounds
Active
Ingredient
(
ai)
Used
11
Wiping
for
Cleaning
Products
Material
Preservatives
Scenario
involves
wiping
with
cleaning
products
containing
the
biocide.
The
Agency
typically
assumes
1liter
or
0.26
gallons
(
where
density
is
assumed
to
be
8.3
lb/
gal;
2.2
lbs)
of
liquid
are
used
by
commercial
handlers.
EPA
Reg
67071­
22
indicates
that
0.15
lb
(
20%
ai)
are
added
to
1,000
lb
of
cleaning
solution.
The
maximum
amount
ingredient
handled
is
0.000066
lb
ai.
Equation
is
as
follows:
2.2
lb
cleaning
solution
x
0.15
lb/
1000
lb
cleaning
solution
x
20%
ai
=
0.000066
lb
ai.

The
Agency
typically
assumes
0.5liter
or
0.13
gallons
(
where
density
is
assumed
to
be
8.3
lb/
gal
1.1
lbs)
of
liquid
are
used
by
residential
handlers.
The
maximum
amount
ingredient
handled
is
0.000033
lb
ai.
Equation
is
as
follows:
1.1
lb
cleaning
solution
x
0.15
lb/
1000
lb
cleaning
solution
x
20%
ai
=
0.000033
lb
ai.

Mopping
for
Cleaning
Products
Material
Preservatives
Scenario
involves
mopping
home
cleaning
products
containing
the
biocide.
The
Agency
typically
assumes
2
gallons
(
where
density
is
assumed
to
be
8.3
lb/
gal;
16.6
lbs)
of
liquid
are
used
by
commercial
handlers.
EPA
Reg
67071­
22
indicates
that
0.15
lb
(
20%
ai)
are
added
to
1,000
lb
of
cleaning
solution.
The
maximum
amount
ingredient
handled
is
0.0005
lb
ai.
Equation
is
as
follows:
16.6
lb
cleaning
solution
x
0.15
lb/
1000
lb
cleaning
solution
x
20%
a
i=
0.0005
lb
ai.

The
Agency
typically
assumes
1
gallon
(
where
density
is
assumed
to
be
8.3
lb/
gal;
8.3
lbs)
of
liquid
are
used
by
residential
handlers.
The
maximum
amount
ingredient
handled
is
0.00025
lb
ai.
Equation
is
as
follows:
8.3
lb
cleaning
solution
x
0.15
lb/
1000
lb
cleaning
solution
x
20%
a
i=
0.00025
lb
ai.

Painting
(
brush/
roller)
Material
Preservatives
Scenario
involves
using
biocide
in
paint.
The
Agency
typically
assumes
5
gallons
with
a
brush/
roller
for
commercial
painters
(
where
paint
density
is
assumed
to
be
10lb/
gal;
50
lbs).
EPA
Reg
67071­
24
indicates
that
1­
5
lb
(
10%
ai)
of
material
preservative
are
used
per
1,000
lb
of
paint.
The
maximum
amount
for
commercial
handlers
is
0.025
lb
ai.
Equation
is
as
follows:
50
lb
paint
x
5
lb/
1,000
lb
paint
x
10%
ai
=
0.025
lb
ai.

The
Agency
typically
assumes
2
gallons
of
paint
for
residential
painters
(
where
paint
density
is
assumed
to
be
10lb/
gal;
20
lbs).
The
maximum
amount
for
residential
handlers
is
0.01
lb
ai.
Equation
is
as
follows
for
residential
handler:
20
lb
paint
x
5
lb/
1,000
lb
of
paint
x
10%
ai
=
0.01
lb
ai.

Airless
Sprayer
Painting
Material
Preservatives
Scenario
involves
using
biocide
in
paint
as
an
in­
can
preservative.
The
Agency
typically
assumes
50
gallons
of
paint
sprayed
by
commercial
painters
(
where
paint
density
is
assumed
to
be
10lb/
gal;
500
lbs).
EPA
Reg
67071­
24
indicates
that
1­
5
lb
(
10%
ai)
of
material
preservative
are
used
per
1,000
lb
of
paint.
The
maximum
amount
for
commercial
painter
is
0.25
lb
ai.
Equation
is
as
follows:
500
lb
paint
x
5
lb/
1,000
lb
paint
x
10%
ai
=
0.25
lb
ai.

The
Agency
typically
assumes
15
gallons
of
paint
sprayed
by
homeowner
(
where
paint
density
is
assumed
to
be
10lb/
gal;
150
lbs).
The
maximum
amount
for
residential
handlers
is
0.075
lb
ai.
Equation
is
as
follows:
150
lb
paint
x
5
lb/
1,000
lb
paint
x
10%
ai
=
0.075
lb
ai.
12
Table
5:
Summary
of
Short­
and
Intermediate­
term
Occupational
and
Residential
Exposures
and
MOEs
Scenarios
Use
Site
Category
Use
Rate
(
lbs
ai/
day)
a
Inhalation
Unit
Exposureb
(
mg/
lb
ai)
Dermal
Unit
Exposureb
(
mg/
lb
ai)
Short­
term
and
Intermediateterm
Inhalation
Dosec
(
mg/
kg/
day)
Short­
term
and
Intermediateterm
Absorbed
Dermal
Dosec
(
mg/
kg/
day)
Short­
and
Intermediateterm
Inhalation
MOEd
Short­
and
Intermediateterm
Dermal
MOEe
Total
MOEf
Occupational
Liquid
Pour
for
Preservatives
Material
Preservatives
5.00
0.00346
0.135
0.00025
0.0040
20,000
1,300
1,200
Industrial
Processes
4.00
0.00346
0.135
0.00020
0.0032
25,000
1,600
1,500
and
Water
Systems
Oil/
gas
Drilling
Fluids
0.01
0.00346
0.135
7E­
7
1E­
5
7E+
6
4.5E+
5
4.2E+
5
Liquid
Pump
Oil/
gas
Drilling
Fluids,

Secondary
Recovery
0.01
0.000403
0.00629
6E­
3
0.039
830
130
110
Liquid
Pour
for
Material
Preservatives
0.81
0.00854
0.184
0.00010
0.00087
51,000
5,700
5,100
Metalworking
Fluids
Wiping
for
Janitorial
Products
Material
Preservatives
0.000066
67.3
2870
6.3E­
05
0.0011
79,000
4,500
4,300
Mopping
for
Material
Preservatives
0.0005
2.38
71.6
1.7E­
05
0.00021
290,000
24,000
22,000
Janitorial
Products
Painting
Material
Preservatives
0.025
0.28
180
0.00010
0.026
50,000
190
190
Airless
Painting
Material
Preservatives
0.25
0.83
38
0.0030
0.056
1,700
90
85
Residential
Wiping
for
Material
Preservatives
3.3E­
05
67.3
2870
3.2E­
05
0.00055
160,000
9,000
8,500
Cleaning
Products
Mopping
for
Material
Preservatives
0.00025
2.38
71.6
8.5E­
06
0.00010
590,000
48,000
44,000
Cleaning
Products
Painting/
brush
Material
Preservatives
0.010
0.28
230
4.0E­
05
0.013
130,000
370
370
Airless
Painting
Material
Preservatives
0.075
0.83
79
0.00089
0.035
5,600
140
140
a
Use
Rate
based
on
label
information
and
assumptions
on
daily
amounts
handled
(
see
Table
4).

b
Unit
exposures
based
on
CMA
and
PHED
data
for
inhalation
and
dermal.
Occupational
PPE
for
the
liquid
pour
includes
long
pants
(
LP),
long
sleeved
shirts(
LS),
and
gloves
(
G),
all
other
scenarios
are
based
on
LP,
SL,
and
no
gloves,
except
for
residential
painting
which
assumes
short­
pants,
short­
sleeved
shirt,
no
gloves.
13
c
Short­
term
and
Intermediate­
term
Inhalation
and/
or
Dermal
Dose
(
mg/
kg/
day)=
Unit
Exposure
(
mg/
lb
ai)
*
Application
Rate
(
lb
ai)/
Body
Weight
(
70
kg).
Note:
41
percent
dermal
absorption
is
used
to
estimate
the
absorbed
dermal
dose.

d
Short­
term
and
Intermediate­
term
Inhalation
MOE=
Inhalation
NOAEL
(
5
mg/
kg/
day)/
Short
and
Intermediate­
term
Inhalation
Dose
(
mg/
kg/
day).
Target
MOE=
1000.

e
Short­
term
and
Intermediate­
term
Dermal
MOE=
Dermal
NOAEL
(
5
mg/
kg/
day)/
Short
and
Intermediate­
term
Abs.
Dermal
Dose
(
mg/
kg/
day).
Target
MOE=
100.

f
Total
MOE
=
NOAEL
5
mg/
kg/
day
/
(
absorbed
dermal
dose
+
inhalation
dose);
where
the
total
target
MOE
=
100.
14
Metal
Working
Fluids
(
Machinists):

The
USEPA/
OPPTS
Chemical
Engineering
Branch
(
CEB)
model
was
used
to
perform
screening­
level
assessments
for
chemicals
in
occupational
settings
(
U.
S.
EPA,
1991).
This
is
the
approach
recommended
by
the
Antimicrobial
Division
(
AD).
The
CEB
model
uses
measured
and/
or
assumed
airborne
oil
mist
concentrations
for
metal
working
operations.
Since
no
measured
concentrations
are
available
for
BIT
the
high­
end
oil
mist
concentration
is
based
on
the
OSHA's
Permissible
Exposure
Limit
(
PEL)
of
5
mg/
m3
(
NIOSH,
1998).
EPA
Reg
72674­
15
indicates
that
0.25%
(
i.
e.,
0.0025)
of
the
label
product
is
added
to
metal
working
fluids
and
of
that,
only
19.3%
is
the
active
ingredient
(
1,2­
benzisothiazolin­
3­
one).
Therefore,
the
upper
bound
air
concentration
of
BIT
that
a
worker
is
exposed
to
is
5
mg/
m3
x
0.0025
x
0.09
or
an
air
concentration
of
0.0011
mg/
m3.
Potential
dose
rates
for
inhalation
were
calculated
as
follows:

ADR
pot
=(
C
x
IR
x
ED
)
/
(
BW)

where:

ADR
pot
=
Acute
potential
dose
rate
(
mg/
kg­
day);

C
=
Concentration
(
mg/
m3);

IR
=
Inhalation
rate
(
m3/
hr);

ED
=
Exposure
duration
(
hrs);

BW
=
Body
weight
(
kg);
and,

The
following
assumptions
were
made:
inhalation
rate
for
adults
­
1.25
m3
/
hr;
exposure
duration
­
8
hours;
and
body
weight
­
70
kg.
Using
this
exposure
algorithm,
the
long­
term
inhalation
dose
was
calculated
to
be
1.6E­
4
mg/
kg/
day,
resulting
in
a
long­
term
inhalation
MOE
of
31,000
which
is
larger
than
the
inhalation
target
MOE
(
1,000).

A
screening­
level
long­
term
dermal
exposure
estimate
was
derived
from
the
2­
Hand
Dermal
Immersion
in
Liquid
Model
in
ChemSTEER
(
EPA/
OPPT).
The
model
is
available
at
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
chemsteer.
htm.
The
weight
fraction
of
BIT
in
metal
working
fluids
is
0.00048
(
0.0025
formulated
product
added
to
oil
x
0.193
ai
in
formulated
product
=
0.00048),
calculated
from
EPA
Reg.
No.
72674­
15.
Based
on
the
model
for
emersion
of
hands
in
metal
working
fluids,
the
long­
term
absorbed
dermal
dose
is
estimated
at
0.025
mg/
kg/
day.
The
longterm
dermal
MOE
is
200
(
i.
e.,
oral
NOAEL
of
5
mg/
kg/
day
/
potential
dose
of
0.025
mg/
kg/
day).
The
dermal
MOE
is
above
the
target
MOE
of
100,
and
therefore,
not
of
concern.
The
total
risk
(
NOAEL
/(
inhalation
dose
+
absorbed
dermal
dose))
for
the
machinist
is
also
presented.
The
total
MOE
for
machinists
is
200,
and
therefore,
not
of
concern.

3.0
Postapplication
Exposures
Postapplication
exposures
refer
to
those
potential
exposures
which
may
occur
to
handlers
while
involved
in
postapplication
or
reentry
activities
following
application
of
the
pesticide
concentrate
or
formulated
end­
use
product.
Postapplication
exposures
to
individuals
can
also
occur
from
contact
15
to
treated
surfaces
and
while
occupying
areas
where
pesticide
end­
use
products
have
recently
been
applied.

Occupational
Postapplication
Exposure
Postapplication
inhalation
exposures
may
occur
in
the
industrial
settings
around
the
water
systems
via
inhalation,
and
dermal
exposures
may
occur
while
maintaining
industrial
equipment.
However,
occupational
postapplication
dermal
and
inhalation
exposures
to
BIT
are
likely
to
be
minimal
compared
to
handler
exposure
because
of
dilution
during
processing
or
during
the
use
of
MWFs
by
machinists.
No
postapplication
exposure
data
have
been
submitted
to
the
agency
to
determine
the
extent
of
postapplication
exposures
in
the
industrial
settings.
Inhalation
exposures
are
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
BIT
is
low.

Residential
Postapplication
Exposure
The
Food
Quality
Protection
Act
(
1996)
sets
an
explicit
standard
for
assessing
risks
from
potential
exposures
to
children.
EPA
must
determine
whether
exposures
to
pesticides
are
safe
for
children
and
includes
an
additional
safety
factor
for
children,
consider
special
sensitivities
and
exposures
to
pesticide
chemicals.
Specifically,
FQPA
requires
EPA
to
give
special
consideration
to
exposure
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
the
pesticide
chemical
residue..."

Postapplication
exposures
to
individuals
can
occur
from
contact
to
treated
surfaces
where
pesticide
end­
use
products
have
recently
been
applied.
The
residential
post­
application
scenarios
considered
in
this
assessment
are
exposure
to
residue
from
hard
surfaces
(
i.
e.,
floors)
that
have
been
mopped
with
a
product
containing
BIT
and
the
residues
from
laundry
additives
(
liquid
laundry
detergents,
fabric
softeners
and
conditioner,
and
stain
removers).
Although
residential
floors
are
believed
to
be
washed/
moped
on
an
intermittent
basis
(
perhaps
weekly),
facilities
such
as
day
care
centers
may
clean
the
floors
more
often.
Therefore,
both
the
short­
and
intermediate­
term
exposure
durations
have
been
presented.

Floor
Cleaner
Dermal
Exposure
There
is
the
potential
for
dermal
exposure
to
toddlers
crawling
on
the
floor.
Although
residential
floors
are
believed
to
be
washed/
moped
on
an
intermittent
basis,
facilities
such
as
day
care
centers
may
clean
the
floors
more
often.
Therefore,
both
the
short­
and
intermediate­
term
exposure
durations
are
assessed.
To
determine
toddler
exposure
to
residues
on
treated
floor,
the
following
equation
was
used:

PDD
FR
x
SA
BW
=
16
where
PDD
=
Potential
daily
dose
FR
=
Flux
rate
of
chemical
from
material
(
mg/
m2/
day)

SA
=
Surface
area
of
the
body
which
is
in
contact
with
floor
(
m2)

BW
=
Body
weight
(
kg)

The
following
conservative
assumptions
were
made
in
calculating
the
exposures/
risks
due
to
limited
data:

°
Toddlers
(
3
years
old)
are
used
to
represent
the
1
to
6
year
old
age
group
and
are
assumed
to
weigh
15
kg,
the
median
for
male
and
female
toddlers
(
USEPA,
2000b).
A
body
surface
area
of
0.657
m2
has
been
assumed,
which
is
the
median
value.

°
Based
on
EPA
Reg
67071­
22
label,
0.15
lb
of
preservative
that
contains
20%
BIT
is
added
to
1000
lb
of
cleaner
(
weight
fraction
=
0.15
lb
product
x
0.2
ai/
1000
lb
cleaner
=
0.00003
or
0.003
percent).
It
was
assumed
that
the
density
of
the
cleaner
is
8.3
lbs/
gal.
Therefore,
the
use
amount
for
the
application
of
treated
cleaning
products
is
0.00025
lb
ai/
gallon
(
weight
fraction
0.00003
x
8.3
lb/
gal
density).
It
was
assumed
that
the
resulting
solution
is
applied
at
a
rate
of
1
gallon
per
1000
sq.
ft.

°
No
data
could
be
found
regarding
the
quantity
of
solution
residue
left
on
the
floor
after
treatment.
It
has
been
assumed
that
25%
of
the
cleaner
remains
after
the
final
mopping.

°
No
transferable
residue
data
were
available
that
could
be
used
to
estimate
the
skin
transfer
of
BIT
from
the
floor.
Therefore,
Residential
SOPs
estimate
of
10%
of
the
amount
on
the
hard
surface
is
available
for
dermal
transfer.

The
calculations
of
the
dermal
dose
and
the
dermal
MOE
are
presented
in
Table
6.
The
dermal
MOE
is
estimated
to
be
9,100
which
is
above
the
target
MOE
of
100,
and
therefore
not
of
concern.

Table
6.
Short­
and
Intermediate­
term
Risks
Associated
with
Postapplication
Dermal
Exposure
on
Treated
Floors.

Parameter
Value
Rationale
Application
Rate
1000
ft2/
gallon
of
solution
USEPA
Assumption
Cleaning
Solution
0.00025
lb
ai/
gallon
Maximum
rate
listed
on
label
(
EPA
Reg.
No.
67071­
22)

Transferable
Residues
(
TR)
0.030
mg/
m2/
day
((
0.00025
lb
ai/
gal)/(
1000ft2/
gal))
*
(
25%
remaining)*
(
10%
transfer)
*
(
Conversion
Factors)

Surface
Area
of
Body
in
Contact
with
Carpet
0.657
m2
Median
surface
area
of
toddler
Parameter
Value
Rationale
17
Body
Weight
15
kg
Median
body
weight
of
toddler
Absorbed
Dermal
Dose
0.00055
mg/
kg/
day
TR
*
SA
*
41%
dermal
abs/
BW
Dermal
NOAEL
5
mg/
kg/
day
Dermal
MOE
9,100
(
Dermal.
NOAEL)
/
(
Abs
Dermal.
Dose).
Target
MOE
=
100.

TR
=
[((
0.00025
lb
ai/
gal
/
1000ft2/
gal)
x
(
454
g/
lb)
x
(
1000
mg/
g)
x
(
1
ft2
/
0.093
m2))
x
(
0.25
remaining)
x
(
0.1
transferable)]

Incidental
Ingestion
In
addition
to
dermal
exposure,
infants
crawling
on
treated
floors
will
also
be
exposed
to
BIT
via
incidental
oral
exposure.
To
calculate
incidental
ingestion
exposure
to
BIT
due
to
hand­
to­
mouth
transfer,
the
scenarios
established
in
the
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments
were
used.
These
scenarios
use
assumptions
that
are
similar
to
those
used
in
calculating
exposures
due
to
dermal
contact
of
BIT
from
toddlers
crawling
on
treated
floors.
The
assumptions
above
in
the
dermal
assessment
(
Table
6)
estimates
the
transferable
residues
as
0.0030
:
g/
cm2
(
equivalent
to
0.030
mg/
m2).
The
estimated
potential
ingestion
dose
rate
immediately
after
application
would
be
calculated
as
follows:

PDR
norm
=
ISR
t
x
SA
x
FQ
x
SE
x
ET
x
0.001
mg/:
g
BW
where:

PDR
norm
=
Potential
dose
rate
(
mg/
kg/
day);

ISR
t
=
Indoor
Surface
Residue
(:
g/
cm2)
at
time
0;

SA
=
Surface
area
of
the
hands
that
contact
both
the
treated
area,
and
the
individuals
mouth
(
cm2/
event);

FQ
=
Frequency
of
hand­
to­
mouth
events
(
events/
hr);

SE
=
Saliva
extraction
efficiency
of
50%;

ET
=
Exposure
Time
(
4
hrs/
day);
and
BW
=
Body
weight
(
15
kg)

Based
on
the
data
provided
in
EPA's
Residential
SOPs,
the
surface
area
used
for
each
hand­
tomouth
event
is
20
cm2.
It
is
assumed
that
there
are
20
hand­
to­
mouth
exposure
events
per
hour
(
90th
percentile)
for
short­
term
exposure
duration
and
9.5
events
per
hour
(
mean)
for
the
intermediate­
term
duration.
The
short­
and
intermediate­
term
incidental
oral
NOAEL
of
5
mg/
kg/
day
(
target
MOE
=
300)
should
be
used
as
the
toxicity
endpoint
for
this
scenario
because
of
the
intermittent
nature
of
cleaning
the
floor.
The
potential
dose
rate
(
PDR)
using
this
equation
is
18
0.00016
mg/
kg/
day
for
short­
term
and
7.7E­
5
mg/
kg/
day
for
the
intermediate­
term
duration
resulting
in
a
hand­
to­
mouth
MOEs
for
toddlers
of
31,000
(
ST)
and
65,000
(
IT).
The
incidental
oral
exposure
is
of
not
concern
(
i.
e.,
above
the
target
MOE
of
300).

The
ARI
methodology
is
used
to
determine
the
total
risk
to
children
playing
on
BIT­
treated
floors
(
i.
e.,
incidental
oral
+
dermal
exposure).
The
short­
term
dermal
MOE
reported
above
is
9,100
(
target
MOE
is
100)
and
the
short­
term
incidental
oral
MOE
is
31,000
(
target
MOE
is
300).
The
ARI
is
48,
and
therefore,
not
of
concern
[
1/((
target
dermal
MOE/
dermal
MOE)
+
(
target
oral
MOE/
oral
MOE)),
ARI
greater
than
1
is
not
of
concern].
Note:
the
intermediate­
term
MOE
is
greater
than
the
short­
term
MOE
because
of
the
frequency
of
hand­
to­
mouth
activities
is
less
over
time
(
90th
percentile
used
for
short­
term
and
mean
used
to
represent
intermediate­
term)
but
the
toxicological
endpoints
are
the
same
for
both
time
periods.

Clothing/
Textile
BIT
labels
also
include
a
microbiocide
use
in
laundry
detergents,
fabric
softeners,
and
stain
removers
(
EPA
Reg.
No.
67071­
23).
To
determine
dermal
and
incidental
oral
exposure
to
treated
clothing,
the
guidance
provided
in
Human
and
Environmental
Risk
Assessment
(
HERA)
Guidance
Document
(
2003)
was
used
for
indirect
skin
contact
from
wearing
clothes
and
oral
exposure
from
mouthing
or
sucking
on
treated
fabric.
HERA
(
2003)
provides
the
following
basic
equations.

Dermal
Exposure
Dermal
Exposure
(
mg/
kg/
day)
=
[((
M
x
F1
x
FD)/
WI)
x
S
der
x
F2
x
F3
x
F4]/
BW
where
M
=
amount
of
undiluted
product
used
(
e.
g.,
laundry
detergent),
150,000
mg
(
HERA
2003)

F1
=
weight
fraction
of
ai
applied
(
EPA
Reg
67071­
23,
0.15%
product
by
weight
x
20%
ai
=
0.03%
or
0.0003),

FD
=
fabric
density
for
mixed
cotton
and
synthetics
(
10
mg/
cm2)
(
HERA
2003),

WI
=
total
weight
of
fabric
estimate
(
1E+
6
mg)
(
HERA
2003),

Sder
=
Surface
area
of
the
body
which
is
in
contact
with
clothing
(
5670
cm2
child
and
16,900
cm2
adult),

F2
=
weight
fraction
transferred
from
clothing
to
skin
(
0.01
or
1%)
(
HERA
2003),

F3
=
weight
fraction
remaining
on
skin
(
1
or
100%)
(
HERA
2003),

F4
=
dermal
absorption
of
BIT
(
0.41
or
41%),
and
BW
=
Body
weight
(
kg)

Ingestion/
Mouthing
19
Oral
Exposure
(
mg/
kg/
day)
=
[((
M
x
F1
x
FD)/
WI)
x
Fm
x
SE]/
BW
where
M
=
amount
of
undiluted
product
used
(
e.
g.,
laundry
detergent),
150,000
mg
(
HERA
2003)

F1
=
weight
fraction
of
ai
applied
(
EPA
Reg
67071­
23,
0.15%
product
by
weight
x
20%
ai
=
0.03%
or
0.0003),

FD
=
fabric
density
for
mixed
cotton
and
synthetics
(
10
mg/
cm2)
(
HERA
2003),

WI
=
total
weight
of
fabric
estimate
(
1E+
6
mg)
(
HERA
2003),

Sder
=
fabric
area
mouthed
(
100
cm2)
(
HERA
2003),

SE
=
saliva
extraction
efficiency
(
1
or
100%)
(
HERA
2003),
and
BW
=
Body
weight
(
15
kg)

Data
on
which
these
calculations
could
be
based
were
generally
unavailable;
therefore,
a
number
of
conservative
assumptions
have
been
made:

(
1)
Toddlers
(
3
years
old)
are
used
to
represent
the
1
to
6
year
old
age
group
and
are
assumed
to
weigh
15
kg,
the
median
for
male
and
female
toddlers
(
USEPA,
2000b).
The
median
surface
area
for
a
3
year
old,
minus
the
head,
is
0.567
m2.
Median
values
for
body
weights
and
surface
areas
for
adults
have
been
used
(
70
kg
and
1.69
m2,
not
including
head
surface
area).

(
2)
No
leaching
data
were
available
that
could
be
used
to
estimate
a
flux
rate
of
the
chemical
from
clothing.
Therefore,
HERA's
assumption
of
1%
transfer
was
used.

(
3)
No
dissipation
data
were
available,
therefore,
the
amount
of
BIT
remaining
on
the
skin
is
assumed
to
be
100
percent.

(
4)
No
information
is
available
to
estimate
the
amount
of
product
remaining
after
a
wash
rinse
cycle.
The
HERC
document
provides
an
estimate
for
this
variable
as
"
the
water
mass
left
after
spin
cycle
(
kg)
/
total
water
mass
initially
present
(
kg)".
This
variable
could
be
estimated
using
default
assumptions
if
risks
were
identified
in
the
future.
Moreover,
the
registrant
indicated
in
the
public
comments
that
"
washing
is
normally
carried
out
at
high
pH,
around
10,
rinsing
is
usually
pH
7
and
softening
at
the
end
of
the
wash
may
be
slightly
acidic,
pH
6
 
7.
Under
all
these
pH
conditions,
BIT
will
not
have
a
positive
charge.
All
of
the
common
fibers
used
for
clothing
have
either
a
negative
charge,
or
are
not
charged.
These
fibers
will
have
no
ionic
attraction
for
BIT.
There
will
not
be
any
significant
hydrogen
bonding
and
BIT
does
not
have
the
extended
planar
aromatic
structure
required
by
dyestuffs
for
substantivity
to
cotton
(
usually
3
or
more
aromatic
rings)
thus
BIT
will
not
be
able
to
"
dye"
the
anionic
or
neutral
fibers.
Under
laundry
conditions,
BIT
will
not
adsorb
onto
any
of
these
fibres.
From
the
above,
BIT
remains
in
the
wash
water
and
the
vast
majority
is
discharged
to
drain
after
draining/
spinning.
Only
a
small
amount
of
BIT
will
be
present
in
the
residual
entrained
wash
water
and
this
will
be
readily
removed
in
any
rinse
cycle.
Since
all
textile
washing
incorporates
some
element
of
rinsing,
it
is
likely
that
the
potential
for
deposited
residues
of
BIT
on
textiles
is
very
low."
Therefore,
the
estimates
provided
below
are
considered
to
be
screening­
level
and
an
overestimate
of
the
true
risks.
20
The
calculation
of
the
short­
and
intermediate­
term
oral
and
dermal
doses
and
MOEs
are
presented
in
Table
7.
The
incidental
oral
MOE
as
a
result
of
mouthing
treated
fabric
is
1,700
and
is
not
of
concern.
The
dermal
MOEs
calculated
for
both
toddler
and
adult
scenarios
are
also
not
of
concern
(
MOEs
=
7,200
and
11,000
for
toddlers
and
adults,
respectively).
However,
the
percent
transfer
of
residues
from
clothing
to
skin
is
considered
a
data
gap
and
is
necessary
to
appropriately
confirm
these
dermal
exposures.

The
ARI
methodology
is
used
to
determine
the
total
risk
to
children
wearing
clothing
treated
with
BIT
(
i.
e.,
incidental
oral
+
dermal
exposure).
The
ARI
is
5.2,
and
therefore,
not
of
concern
[
i.
e.,
1/((
target
dermal
MOE/
dermal
MOE)
+
(
target
oral
MOE/
oral
MOE)),
ARI
greater
than
1
is
not
of
concern].
21
Table
7.
Short­
and
Intermediate­
term
Risks
Associated
with
Postapplication
Exposure
to
Laundered
Clothing
Parameter
3­
yr
old
Toddler
Adult
Rationale
Body
Weight
15
kg
70
kg
Median
body
weight
Surface
area,
minus
head
5,670
cm2
16,900
cm2
Median
surface
area
Surface
area
of
cloth
mouthed
100
cm2
NA
HERA
2003
Concentration
on
clothing
4.5E­
4
mg/
cm2
(
150,000
mg
product
x
0.03%
ai
x
10
mg/
cm2
cloth
density)/
1E+
6
mg
weight
of
fabric.
EPA
Reg.
No.
67071­
23.
Note:
Some
fraction
of
the
chemical
is
lost
due
to
the
rinse
cycle
in
the
wash
but
there
are
no
data
at
this
time
to
estimate
the
amount.

Daily
Dermal
Dose
0.00070
mg/
kg/
day
0.00045
mg/
kg/
day
(
concentration
on
clothing
mg/
cm2
x
surface
area
cm2
x
transfer
efficiency
1%
to
skin
and
100%
to
mouth)
*
(
41%
dermal
absorption
or
100%
oral
absorption)
/
Body
Weight
Incidental
Oral
Ingestion
(
mouthing)
0.003
mg/
kg/
day
NA
(
Qty.
a.
i.)
/
(
Body
Weight)

Dermal
NOAEL
5
mg/
kg/
day
Oral
endpoint
selected
Oral
NOAEL
5
mg/
kg/
day
Oral
endpoint
selected
Dermal
MOE
7,200
11,000
(
NOAEL)
/
(
Dose).
Target
MOE
=
100.

Incidental
Oral
MOE
(
mouthing)
1,700
NA
(
NOAEL)
/
(
Dose).
Target
MOE
=
300.

4.0
Summary
of
Data
Gaps
and
Uncertainties
Toxicology
°
For
inhalation,
the
uncertainty
factor
or
"
target"
margin
of
exposure
(
MOE)
of
100
is
based
on
10x
for
differences
among
humans
(
intra
species
variability)
and
10x
for
differences
between
the
test
animals
and
humans
(
inter
species
extrapolation).
Because
of
the
need
for
route­
to­
route
extrapolation,
an
additional
10x
uncertainty
factor
is
applied
to
determine
if
a
route­
specific
inhalation
toxicological
study
is
warranted
(
i.
e.,
if
estimated
inhalation
MOEs
are
greater
than
1000,
an
inhalationspecific
toxicological
study
will
not
be
needed).
22
°
For
dermal,
the
uncertainty
factor
or
"
target"
margin
of
exposure
(
MOE)
of
100
is
based
on
10x
for
differences
among
humans
(
intra
species
variability)
and
10x
for
differences
between
the
test
animals
and
humans
(
inter
species
extrapolation).

°
For
oral,
the
uncertainty
factor
or
"
target"
margin
of
exposure
(
MOE)
of
300
is
based
on
10x
for
differences
among
humans
(
intra
species
variability)
and
10x
for
differences
between
the
test
animals
and
humans
(
inter
species
extrapolation),
and
3x
for
data
base
uncertainty
factor.

°
The
dermal
absorption
factor
of
41
percent
was
not
adjusted
to
account
for
the
potential
reduction
of
the
bioavailability
of
BIT
in
paint
because
of
a
lack
of
chemical­
specific
data.
It
is
believed
that
the
paint
matrix
has
the
potential
to
reduce
the
dermal
exposure.

Handler
Exposure
Estimates
°
The
maximum
use
amounts
provided
by
labels
were
used
to
assess
the
overall
amount
of
preservative
handled.

°
The
dermal
exposure/
risks
for
the
residential
clothing
scenario
utilized
HERA's
assumption
of
1%
residue
transferred
from
clothing.
However,
based
on
the
conservative
assumptions
in
this
scenario
(
i.
e.,
BIT
does
not
adsorb
to
clothing
and
the
assessment
does
not
account
for
the
residues
lost
during
a
washing
rinse
cycle),
confirmatory
data
on
residue
transfer
is
not
necessary
to
support
this
percent
transfer
parameter.

°
For
screening
assessments,
the
Agency
typically
may
have
to
make
professional
judgements
on
the
amount
of
substance
that
is
used
by
a
handlers
in
a
work
day
for
a
particular
antimicrobial
use
unless
the
registrants
have
provided
information
in
meetings
with
the
Agency
or
have
expressed
assumptions
in
written
memos
or
documentation
provided
to
the
Agency.
The
Agency
typically
makes
professional
judgement
assumptions
that
are
assumed
to
be
upper
bound
estimates.

°
There
are
no
representative
unit
exposure
data
for
chemical
metering
into
secondary
recovery
oil
operations.
Because
the
volume
of
water
being
treated
in
secondary
recovery
operations
is
so
large,
the
available
CMA
data
can
not
be
reliably
extrapolated
without
the
potential
to
overestimate
the
exposure.
However,
for
BIT,
even
when
the
exposures
are
extrapolated
to
the
large
volumes
in
the
secondary
recovery
oil
operation,
the
MOEs
are
not
of
concern.

Chemical
Manufacturers
Association
(
CMA)
Data
No
chemical­
specific
handler
or
postapplication
exposure
data
are
available.
Surrogate
dermal
and
inhalation
data
from
Chemical
Manufacturers
Association
(
CMA)
and
PHED
databases,
were
used
to
assess
handler
exposure.
Note
that
CMA
surrogate
data
have
the
following
deficiencies:

°
The
inhalation
concentrations
were
typically
below
the
detection
limits,
so
the
unit
exposures
for
the
inhalation
exposure
route
could
not
be
accurately
calculated.
23
°
The
quality
of
the
CMA
data
may
have
QA/
QC
problems
including
lack
of
either/
or
field
fortification,
laboratory
recoveries,
and
storage
stability
information
and
the
insufficient
amount
of
replicates.

Post­
Application
Scenarios
°
Since
no
measured
use
concentrations
are
available
for
BIT,
the
high­
end
oil
mist
concentration
is
based
on
the
OSHA's
Permissible
Exposure
Limit
(
PEL)
of
5
mg/
m3.
The
upper
bound
air
concentration
of
BIT
that
a
worker
is
exposed
to
is
5
mg/
m3
times
0.36%
times
9%
or
an
air
concentration
of
0.00162
mg/
m3.

5.0
REFERENCES
HERA,
2003.
Human
and
Environmental
Risk
Assessment,
Guidance
Document
Methodology,
April
22,
2002
(
http://
www.
heraproject.
com/
files/
Guidancedocument.
pdf).

NIOSH,
1998.
NIOSH
Pocket
Guide
to
Chemical
Hazard.
U.
S
Department
of
Health
and
Human
Services.
Centers
for
Disease
Control.
www.
cdc.
gov/
niosh/
npg/
npgd0472.
html.

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

U.
S.
EPA.
1991.
Chemical
Engineering
Branch
Manual
for
the
Preparation
of
Engineering
Assessments.
Prepared
for
the
OPPT
by
IT
Environmental
Programs,
Inc.

U.
S.
EPA,
1997a.
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments.
Prepared
for
the
Office
of
Pesticide
Programs,
Health
Effects
Division.
Contract
No.
68­
W6­
0030.

U.
S.
EPA,
1997b.
Exposure
Factors
Handbook.
Volume
I­
II.
Office
of
Research
and
Development.
Washington,
D.
C.
EPA/
600/
P­
95/
002Fa.

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.
2000.
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments.
Office
of
Pesticide
Programs,
Health
Effects
Division.
April
2000.
24
U.
S.
EPA,
2005.
1,2­
Benzisothiazolin­
3­
one
­
Revised
Report
of
the
Antimicrobials
Division's
Toxicology
Endpoint
Selection
Committee
(
ADTC),
dated
April
22,
2005.