Document ID: EPA-HQ-OPP-2005-0200-0014
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-22T05:00Z

1,2­
Benzisothiazolin­
3­
one
(
BIT)
Risk
Assessment
Antimicrobials
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
1921
Jefferson
Davis
Highway
Arlington,
VA
22202
September
8,
2005
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
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1
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
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9
2.1
Chemical
Identification
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9
2.2
Physical/
Chemical
Properties
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9
3.0
ENVIRONMENTAL
FATE
ASSESSMENT
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10
4.0
HAZARD
CHARACTERIZATION
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10
4.1
Hazard
Profile
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10
4.2
FQPA
Considerations
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15
4.3
Dose­
Response
Assessment
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16
4.4
Endocrine
Disruption
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17
5.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
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18
5.1
Summary
of
Registered
Uses
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18
5.2
Dietary
Exposure/
Risk
for
Active
Ingredient
Uses
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18
5.2.1
Residue
Profile
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19
5.2.2
Acute
Dietary
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19
5.2.3
Chronic
Dietary
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19
5.2.4
Cancer,
Dietary
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20
5.3
Dietary
Exposure/
Risk
for
Inert
Ingredient
Uses
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20
5.4
Drinking
Water
Exposures
and
Risks
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23
5.5
Residential
Exposure/
Risks
for
Active
Ingredient
Uses
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24
5.5.1
Residential
Handler
Scenarios
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24
5.5.1.1
Paint
Exposures
and
Risks
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24
5.5.1.2
Cleaning
Product
Exposures
and
Risks
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25
5.5.2
Residential
Post­
application
Exposure
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26
5.6
Residential
Exposure
and
Risks
From
Inert
Ingredient
Uses
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31
6.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS
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36
6.1
Acute
and
Chronic
Risk
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37
6.2
Short­
and
Intermediate­
Term
Aggregate
Exposures
and
Risks
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38
7.0
CUMULATIVE
RISK
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42
8.0
OCCUPATIONAL
EXPOSURE
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43
8.1
Occupational
Handler
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43
8.2
Occupational
Post­
application
Exposure
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46
9.0
ECOTOXICOLOGY
ASSESSMENT
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47
10.0
DATA
NEEDS
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50
11.0
INCIDENT
REPORT
ASSESSMENT
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50
REFERENCES
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51
1
1.0
EXECUTIVE
SUMMARY
1,2­
benzisothiazolin­
3­
one
(
BIT)
is
an
antimicrobial
that
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,
laundry
detergents,
fabric
softeners,
stain
removers,
inks,
photographic
processing
solutions,
paints
and
stains,
titanium
dioxide
slurries,
oil
in
water
emulsions,
latices,
metalworking
fluids,
casein/
rosin
dispersions,
textile
spin­
finish
solutions,
pesticide
formulations,
tape
joint
compound,
leather
processing
solutions,
preservation
of
fresh
animal
hides
and
skins,
and
for
offshore
and
terrestrial
gas/
oil
drilling
muds
and
packer
fluids
preservation.
The
specific
antimicrobial
use
categories
include
the
following
general
use
patterns:
material
preservatives
(
indoor
food
and
indoor/
outdoor
non­
food),
industrial
processes
and
water
systems
(
indoor
nonfood),
and
indoor
and
outdoor
residential
uses.
1,2­
benzisothiazolin­
3­
one
is
also
used
as
an
inert
ingredient
in
a
variety
of
products
as
a
materials
preservative.
Residential
and
occupational
exposures
and
risks
from
the
use
of
products
containing
1,2­
benzisothiazolin­
3­
one
as
both
the
active
and
inert
ingredients
are
assessed
in
this
risk
assessment.

Environmental
Fate:
The
environmental
fate
assessment
for
1,2­
benzisothiazolin­
3­
one
is
based
on
limited
information;
data
are
only
available
for
hydrolysis,
aerobic
soil
metabolism,
and
adsorption/
desorption.
These
data
indicate
that
1,2­
benzisothiazolin­
3­
one
is
hydrolytically
stable
(
half­
life
>
30
days),
but
breaks
down
fairly
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
1,2­
benzisothiazolin­
3­
one
shows
moderate
binding
to
soils,
with
adsorption
K
d
values
estimated
to
be
between
1.24
to
9.56.
If
used
outdoors,
1,2­
benzisothiazolin­
3­
one
may
possibly
move
with
soil
during
rainfall
events
and
potentially
reach
surface
waters.
However,
with
a
K
ow
value
of
20
at
25
o
C,
1,2­
benzisothiazolin­
3­
one
is
unlikely
to
bioaccumulate
in
aquatic
organisms.

Hazard:
Acute
toxicity
data
show
that
1,2­
benzisothiazolin­
3­
one
is
moderately
toxic
by
the
oral
and
dermal
routes
(
Toxicity
Category
III
for
both
studies),
but
also
show
that
this
chemical
is
a
severe
eye
irritant
(
Toxicity
Category
I).
Data
from
acute
dermal
irritation
studies
indicate
only
mild
skin
irritation
(
Toxicity
Category
IV),
but
repeated
dermal
application
indicates
a
more
significant
skin
irritation
response.
This
response
could
be
related
to
the
ability
of
this
chemical
to
cause
a
moderate
skin
sensitization.

Subchronic
oral
toxicity
studies
conducted
in
both
rats
and
dogs
show
systemic
effects
after
repeated
oral
administration.
In
rats,
decreased
body
weight
was
observed
in
males
at
weeks
2,
3,
and
13
as
well
as
an
increased
incidence
of
forestomach
hyperplasia
at
a
dose
of
69
mg/
kg/
day.
In
a
second
subchronic
oral
study,
in
which
rats
received
gavage
doses
of
1,2­
benzisothiazolin­
3­
one,
stomach
lesions
were
observed
at
doses
of
30
mg/
kg
and
higher.
A
90
day
dermal
toxicity
study
in
rats
was
conducted;
however,
although
this
study
was
classified
as
acceptable,
a
NOAEL
was
not
obtained
based
on
the
presence
of
stomach
lesions,
suggestive
of
oral
exposure
to
the
compound,
at
all
doses
tested
(
100,
300
and
1000
mg/
kg).
In
dogs,
the
2
effects
of
repeated
oral
dosing
of
1,2­
benzisothiazolin­
3­
one
occur
at
lower
doses
than
in
rats,
and
include
alterations
in
blood
chemistry
(
decreased
plasma
albumin,
total
protein,
and
alanine
aminotransferase)
and
increased
absolute
liver
weight
at
a
dose
of
20
mg/
kg/
day.

Two
developmental
toxicity
studies
were
conducted
in
rats
with
1,2­
benzisothizolin­
3­
one.
One
study
was
conducted
with
test
material
of
73.4%
purity,
and
maternal
effects
included
decreased
body
weight
gain
during
dosing
and
decreased
food
consumption
at
a
dose
of
100
mg/
kg/
day.
The
other
study
was
conducted
with
test
material
of
100%
purity,
and
maternal
effects
in
this
study
consisted
of
clinical
toxicity
signs
(
audible
breathing,
haircoat
staining
of
the
anogenital
region,
dry
brown
material
around
the
nasal
area)
as
well
as
increased
mortality
at
a
dose
of
30
mg/
kg/
day.
In
both
studies,
however,
reported
developmental
effects
are
similar
although
occurring
at
different
effect
levels,
and
consist
of
increases
in
skeletal
abnormalities
(
extra
sites
of
ossification
of
skull
bones,
unossified
sternebra)
but
not
external
or
visceral
abnormalities.
Despite
the
differences
in
purity
of
the
test
material
in
the
two
studies,
the
effect
levels
at
which
fetal
effects
occur
are
similar
in
both
studies
(
90
and
100
mg/
kg/
day).
The
maternal
effects
were
however,
substantially
different
(
increased
mortality
at
30
mg/
kg/
day
and
body
weight
changes
at
100
mg/
kg/
day).

In
a
two
generation
reproduction
study
in
rats,
there
is
no
indication
of
increased
sensitivity
to
offspring,
as
the
observed
effects
in
offspring
(
delayed
balanopreputial
separation,
impaired
growth
and
reduced
pup
survival)
occurred
at
doses
that
were
in
excess
of
the
dose
of
1,2­
benzisothiazolin­
3­
one
associated
with
parental
toxicity.

A
dermal
penetration
study
was
conducted
in
rats
which
demonstrated
that
when
1,2­
benzisothiazolin­
3­
one
is
applied
dermally,
a
maximum
of
40.6%
(
41%)
of
the
labeled
material
is
absorbed
after
72
hours.

Mutagenicity
studies
assessing
point
mutations
(
Ames
test
and
mouse
lymphoma
test),
micronucleus
formation,
and
unscheduled
DNA
synthesis
were
also
conducted
for
1,2­
benzisothiazolin­
3­
one.
All
of
these
studies
show
a
negative
mutagenic
response
for
this
chemical.

Toxicity
Endpoints:
The
toxicity
endpoints
used
in
this
document
to
assess
potential
risks
include
acute
and
chronic
dietary
reference
doses
(
RfDs),
and
short­,
intermediate­
and/
or
long­
term
incidental
oral,
dermal,
and
inhalation
doses.
The
endpoints
selected
were
reviewed
by
the
Antimicrobial
Division's
Toxicology
Endpoint
Selection
Committee
(
ADTC)
in
2002
and
2005.

Dietary
Endpoints:
The
acute
and
chronic
RfDs
are
0.017
mg/
kg/
day.
These
endpoints
are
based
on
a
subchronic
toxicity
study
in
dogs
with
a
reported
NOAEL
of
5
mg/
kg/
day
and
which
indicated
increased
incidences
of
emesis
and
clinical
chemistry
alterations
at
the
LOAEL
of
20
mg/
kg/
day.
An
uncertainty
factor
of
300
(
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variability,
and
3x
for
database
uncertainty)
was
applied
to
the
NOAEL
to
obtain
the
3
acute
and
chronic
RfDs.
The
data
base
uncertainty
factor
of
3x
is
applied
to
account
for
oral
data
base
concerns
based
on
the
lack
of
reliable
developmental
toxicity
data
with
respect
to
maternal
toxicity.

Oral
Endpoints:
The
short­
and
intermediate­
term
oral
endpoint
is
5
mg/
kg/
day
and
is
based
on
increased
incidence
of
emesis
and
clinical
chemistry
alterations
at
20
mg/
kg/
day
in
a
subchronic
toxicity
study
in
dogs.
The
target
margin
of
exposure
(
MOE)
is
300.

Dermal
Endpoints:
The
short­,
intermediate­,
and
chronic­
term
dermal
endpoint
is
5
mg/
kg/
day
and
is
based
on
increased
incidence
of
emesis
and
clinical
chemistry
alterations
at
20
mg/
kg/
day
in
an
oral
subchronic
toxicity
study
in
dogs.
The
target
MOE
is
100
for
residential
and
occupational
exposure.
A
41%
dermal
absorption
value
is
used
for
an
oral
to
dermal
route
extrapolation.

Inhalation
Endpoints:
The
short­,
intermediate­,
and
chronic­
term
inhalation
endpoint
is
5
mg/
kg/
day
and
is
based
on
increased
incidence
of
emesis
and
clinical
chemistry
alterations
at
20
mg/
kg/
day
in
a
subchronic
toxicity
study
in
dogs.
The
target
MOE
is
100
for
occupational
and
residential
exposure;
however
if
the
resulting
MOE
is
not
at
least
1000,
the
Agency
can
request
a
repeat
dose
inhalation
study
of
at
least
28
days
in
duration.
(
The
MOE
of
1000
is
based
on
the
application
of
a
10X
uncertainty
factor
for
interspecies
extrapolation,
a
10X
uncertainty
for
intraspecies
variability
and
a
10X
for
the
lack
of
an
inhalation
study).

FQPA
Safety
Factor:
Initially,
on
August
28,
2002
the
ADTC
reviewed
the
available
toxicology
data
for
1,2­
benzisothiazolin­
3­
one
and
recommended
that
the
special
hazard­
based
FQPA
safety
factor
of
10x
be
retained.
This
conclusion
is
based
on
the
lack
of
a
reproduction
toxicity
study,
which
is
a
required
study
for
food­
contact
uses,
the
lack
of
a
developmental
toxicity
study
in
a
non­
rodent
species,
concerns
for
the
discrepancies
in
maternal
effect
levels
between
the
two
developmental
toxicity
studies
in
rats,
the
expected
daily
dietary
exposure
to
this
chemical
from
the
indirect
food
contact
uses,
and
the
gastrointestinal
irritancy
of
this
chemical
as
observed
in
the
submitted
database.
The
initial
retention
of
the
10x
factor
to
address
FQPA
concerns
is
intended
to
account
for
both
the
database
deficiencies
as
well
as
potential
sensitivity
issues,
and
is
consistent
with
the
Antimicrobials
Division's
interim
working
policy
on
indirect
food
uses
of
antimicrobial
pesticides.

The
ADTC
revisited
their
decision
on
February
9,
2005,
after
receiving
additional
data
which
included
a
multi­
generational
reproduction
study,
a
dermal
penetration
study
and
a
90
oral
gavage
study.
At
this
meeting
the
10x
factor
was
reduced
to
1X.
While
sensitivity
issues
were
addressed
by
the
new
data,
there
were
still
data
base
deficiencies
relative
to
the
maternal
toxicity
in
the
developmental
toxicity
studies;
thus
a
3X
database
uncertainty
factor
was
applied
to
the
oral
route
of
exposure.

Based
on
Agency
policy,
a
RfD
modified
by
a
FQPA
safety
factor
is
a
population
adjusted
dose
(
PAD).
The
Agency
calculated
an
acute
PAD
and
a
chronic
PAD,
and
used
this
value
to
4
estimate
acute
and
chronic
dietary
risk.
The
acute
PAD
is
the
acute
RfD
divided
by
the
FQPA
safety
factor.
The
chronic
PAD
is
the
chronic
RfD
divided
by
the
FQPA
safety
factor.

Dietary
Exposure:
The
Agency
has
conducted
a
dietary
exposure
and
risk
assessment
for
use
of
1,2­
benzisothiazolin­
3­
one
as
a
pulp
and
paper
mill
slimicide,
and
a
preservative
in
paper
coatings
and
paper
adhesives,
all
of
which
may
end
in
indirect
food
contact
scenarios.
For
both
the
acute
and
chronic
dietary
exposure,
the
risk
is
highest
for
children
(
21.8%
of
the
acute
and
chronic
PAD).
For
an
adult,
the
acute
and
chronic
dietary
exposure
is
9.4%
of
the
acute
and
chronic
PAD.
All
dietary
exposures
calculated
are
below
the
Agency's
level
of
concern
(
100%
of
aPAD
or
cPAD).
Furthermore,
given
the
conservative
nature
of
the
assumptions
used
in
the
inert
dietary
exposure
and
risk
assessment,
risks
of
concern
from
food
are
not
likely
from
the
use
of
1,2­
benzisothiazolin­
3­
one
as
inert
ingredients
in
pesticide
products.

Water
Exposure
and
Risk:
Based
on
environmental
fate
data,
1,2­
benzisothiazolin­
3­
one
binds
moderately
with
soil
and
may
potentially
move
with
the
soil
during
rainfall
events
and
reach
surface
waters.
Although,
1,2­
benzisothiazolin­
3­
one
has
been
shown
to
be
hydrolytically
stable
with
a
half
life
of
>
30
days,
it
breaks
down
fairly
quickly
in
aerobic
soils.
Outdoor
use
patterns
of
1,2­
benzisothiazolin­
3­
one
which
may
lead
to
contact
with
soil
and/
or
surface
water
include:
1)
the
application
of
agricultural
pesticides
that
contain
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient,
and
2)
the
application
of
paints
that
contain
1,2­
benzisothiazolin­
3­
one.
Considering
1,2­
benzisothiazolin­
3­
one
readily
biodegrades
and
the
small
amount
(
0.02
lbs.
per
acre)
that
may
be
applied
to
crops
via
the
inert
use
and
the
small
amount
likely
to
come
into
contact
with
soils/
surface
waters
via
the
paint
use,
1,2­
benzisothiazolin­
3­
one
is
not
likely
to
be
present
in
food
or
drinking
water
sources
at
substantial
concentrations.

Residential
Exposure
and
Risk:
1,2­
benzisothiazolin­
3­
one
may
be
added
to
residential
household
cleaning
and
paint
products
to
control
bacteria
and
fungi.
The
residential
handler
scenarios
evaluated,
which
are
considered
to
be
representative
of
all
possible
exposure
scenarios,
include:
1)
dermal
and
inhalation
exposure
during
handling
of
BIT­
containing
paint
through
brush/
roller
and
airless
spray
application
methods,
and
2)
dermal
and
inhalation
exposure
during
handling
of
BIT­
containing
cleaning
products
through
wiping
and
mopping
application
methods.
The
scenarios
were
evaluated
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs),
product
label
maximum
application
rates,
related
used
information,
Agency
standard
assumptions,
Pesticide
Handlers
Exposure
Database
(
PHED)
unit
exposure
data,
and
Chemical
Manufacturing
Association
(
CMA)
unit
exposure
data.
None
of
the
residential
handler
exposure
scenarios
exceeded
the
Agency's
level
of
concern
(
i.
e.,
dermal
and
inhalation
MOEs
are
greater
than
the
target
MOE
of
100).

Short­
and
intermediate­
term
residential
postapplication
exposures
considered
in
this
assessment
include
exposure
to
residues
from
hard
surfaces
(
floors)
that
have
been
mopped
with
BIT­
containing
products
and
exposure
to
clothing
laundered
with
1,2­
benzisothiazolin­
3­
one
preserved
detergents.
None
of
the
dermal
or
incidental
oral
scenarios
exceeded
the
Agency's
level
of
concern.
5
1,2­
benzisothiazolin­
3­
one
is
also
used
as
a
materials
preservative
inert
ingredient
in
various
types
of
products
including
turf
insecticides,
fungicides
and
herbicides;
garden
and
ornamental
insecticides;
flea
and
tick
control
products
for
pets;
indoor
crack
and
crevice
insecticides;
paints;
and
household
cleaners.
A
representative
subset
of
these
products
was
assessed
for
the
potential
exposure
to
BIT­
residues
when
used
as
an
inert
ingredient.
These
exposure
scenarios
included
residential
handlers
of
turf,
garden,
and
pet
products
as
well
as,
toddler
post­
application
exposure
to
residues
from
use
of
turf
and
pet
products.
The
scenarios
were
evaluated
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs),
product
label
maximum
application
rates,
related
used
information,
Agency
standard
assumptions,
and
the
Agency's
inert
screening
level
model
PiRat.
None
of
the
residential
handler
exposure
scenarios
exceeded
the
Agency's
level
of
concern.
Although
most
of
the
postapplication
exposures
did
not
exceed
the
Agency's
level
of
concern,
the
toddler
post­
application
dermal
exposure
scenario
to
residues
remaining
on
pets
resulted
in
a
MOE
of
33
which
is
lower
than
the
target
MOE
of
100.
Therefore,
this
scenario
results
in
risks
of
concern
and
requires
further
refinement
and/
or
mitigation.
The
registrant
indicated
that
there
is
the
potential
to
reduce
the
amount
of
BIT
in
pet
products.
If
the
amount
of
BIT
is
reduced
from
0.1
percent
to
0.032
percent
there
would
be
no
risks
of
concern.

Aggregate
Exposure
and
Risk:
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
Since
1,2
benzisothiazolin­
3­
one
has
one
inert
ingredient
exemption
from
the
requirement
of
a
tolerance
for
residues
under
40
CFR
part
180.920
for
growing
crops
and
the
Agency
currently
has
a
petition
for
BIT
as
an
inert
ingredient,
exemptions
from
the
requirement
of
a
tolerance
for
residues
under
40CFR
part
180.930
for
livestock
animals,
the
standards
of
FQPA
must
still
be
met,
including
"
that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).
Aggregate
risk
assessments
were
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
6
months
to
lifetime)
exposures.

The
acute
and
chronic
aggregate
risk
assessments
generally
include
only
dietary
and
drinking
water
exposures.
Since
drinking
water
exposure
is
not
expected
from
any
of
the
indoor
or
outdoor
uses
of
1,2­
benzisothiazolin­
3­
one,
as
either
an
inert
or
active
ingredient,
the
acute
and
chronic
aggregate
assessments
only
included
dietary
exposures
from
the
active
indirect
food
uses
(
i.
e.,
use
in
food­
contact
packaging)
and
inert
dietary
exposures
from
agricultural
pesticide
uses.
The
acute
and
chronic
aggregate
risk
estimates
associated
with
1,2­
benzisothiazolin­
3­
one
are
well
below
the
Agency's
level
of
concern
where,
the
adult's
risks
were
17.1%
of
the
aPAD
and
12.2%
of
the
cPAD,
and
the
children's
risks
were
44.1%
of
the
aPAD
and
31.8%
of
the
cPAD.
6
The
short­
and
intermediate­
term
aggregate
assessments
were
conducted
for
adults
and
children.
The
following
representative
scenarios
were
included
in
the
aggregate
assessments:

Short­
term,
Adults:
°
dietary,
inert
and
active
°
handling
cleaning
products
via
wiping
°
handling
cleaning
products
via
mopping
°
wearing
clothing
washed
in
detergent
preserved
with
BIT
Short­
term,
Children:
°
dietary,
inert
and
active
°
post­
application
exposure
to
cleaning
product
residues
via
mopping
°
wearing
clothing
washed
in
detergent
preserved
with
BIT
Intermediate­
term,
Adults:
°
dietary,
inert
and
active
°
wearing
clothing
washed
in
detergent
preserved
with
BIT
Intermediate­
term,
Children:
°
dietary,
inert
and
active
°
post­
application
exposure
to
cleaning
product
residues
via
mopping
°
wearing
clothing
washed
in
detergent
preserved
with
BIT
Since
the
toxicity
endpoints
for
all
of
the
routes
of
exposure
(
oral,
dermal
and
inhalation)
are
based
on
the
same
study
and
same
toxic
effect,
all
routes
are
aggregated
together.
However,
the
aggregate
risk
index
(
ARI)
method
was
utilized
in
the
assessment.
This
method
was
used
because
the
oral,
dermal
and
inhalation
endpoints
have
different
uncertainty
factors
that
need
to
be
applied.
For
1,2­
benzisothiazolin­
3­
one,
all
endpoints
for
exposure
were
derived
from
a
subchronic
oral
study
in
dogs
however,
the
uncertainty
factors
(
i.
e.,
target
MOEs)
for
oral,
dermal
and
inhalation
routes
are
300,
100
and
100,
respectively.
A
risk
index
$
1
indicates
no
risk
of
concern.
The
short­
term
ARIs
for
adults
and
children
were
6.8
and
1.9,
respectively,
while
the
intermediate­
term
ARIs
for
adults
and
children
were
7.5
and
1.9,
respectively.
These
ARIs
indicate
that
there
is
reasonable
certainty
of
no
harm
from
using
1,2­
benzisothiazolin­
3­
onecontaining
products.

Occupational
Exposure
and
Risk:
The
Agency
has
determined
that
there
is
potential
for
worker
exposure
to
1,2­
benzisothiazolin­
3­
one
through
mixing,
loading,
application,
and
handling
activities.
Dermal
and
inhalation
exposures
from
contact
with
1,2­
benzisothiazolin­
3­
one
were
assessed
for
the
following
scenarios:

Formulated
Product
Handlers
°
Pouring
the
liquid
biocide
preservative
into
industrial
process
intermediate
materials
(
dispersions,
slurries,
emulsions,
solutions,
etc.)
°
Pouring
the
liquid
biocide
preservative
into
industrial
process
water
for
leather
and
photo
processing
systems
7
°
Pouring
the
biocide
into
metalworking
fluid
°
Pouring
the
biocide
during
oil
field
activities
Materials
Preservative
Handlers
°
Handling
BIT­
containing
paint
through
brush/
roller
and
airless
sprayer
application
methods
°
Handling
BIT­
containing
cleaning
products
through
low
pressure
spray,
wipe,
and
mopping
application
methods
°
Handling
BIT­
containing
metalworking
fluids
during
machinist
activities
Materials
preservative
handler
scenarios
were
not
assessed
for
the
application
of
building
materials
because
based
on
end­
use
product
application
methods
and
use
amounts,
the
Agency
assumes
that
exposures
while
applying
paints
will
be
equal
to
or
greater
than
exposures
while
applying
building
materials.

The
inhalation
exposures
are
not
of
concern
for
the
any
of
the
handler
scenarios
assessed.
However,
for
handlers
using
BIT­
treated
paint
via
an
airless
sprayer,
the
dermal
MOE
of
90
indicates
a
risk
of
concern
(
i.
e.,
MOEs
<
100).
However,
these
risk
estimates
are
based
on
a
number
of
conservative
assumptions.
For
example,
the
unit
exposure
values
used
in
the
assessment
do
not
consider
the
use
of
personal
protection
equipment
such
as
gloves
or
respirators,
which
are
often
recommend
by
paint
manufacturers,
especially
for
airless
spray
equipment
applications.
Moreover,
100
percent
dermal
bioavailability
was
assumed
for
BIT
contained
in
a
paint
matrix,
which
is
believed
to
be
an
overestimate.

Occupational
by­
stander/
post­
application
dermal
and
inhalation
exposures
are
limited
to
mists,
steams,
or
vapors
resulting
from
manufacturing
process
operations.
The
dermal
exposures
are
likely
to
be
minimal
because
of
the
dilution
during
processing
or
compared
to
the
metal
working
fluid
machinist.
Inhalation
exposures
are
also
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
1,2­
benzisothiazolin­
3­
one
is
very
low.

Ecological
Hazard
and
Risk:
The
available
ecological
effects
data
for
1,2­
benzisothiazolin­
3­
one
are
somewhat
limited.
Based
on
acute
toxicity
information,
1,2­
benzisothiazolin­
3­
one
displays
low
to
moderate
toxicity
to
birds
and
mammals.
It
is
moderately
toxic
to
freshwater
fish
and
invertebrates,
slightly
toxic
to
marine/
estuarine
fish,
and
highly
toxic
to
marine/
estuarine
invertebrates.

The
indoor
uses
of
BIT
considered
in
this
RED
make
it
unlikely
that
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms
would
occur.
Facilities
using
BIT
for
indoor
industrial
applications
are
required
to
have
NPDES
permits
before
discharging
effluents
into
receiving
waters.
The
potential
exposure
to
terrestrial
and
aquatic
species
from
the
oil
recovery
uses
of
BIT
cannot
be
estimated
at
this
time,
as
there
is
currently
no
validated
model
available
for
such
a
purpose.
The
high
toxicity
of
BIT
to
green
algae
and
invertebrate
species
suggests
that
potential
adverse
acute
effects
could
occur
to
some
species
if
environmental
contamination
from
BIT­
treated
oil
recovery
fluids
occurs.
8
1,2­
benzisothiazolin­
3­
one
is
used
as
an
inert
ingredient
in
pesticide
products
but
the
allowable
amount
that
can
be
applied
is
small
(
not
more
than
0.1%
formulation
and
0.02
lbs.
per
acre).
Data
indicate
that
1,2­
benzisothiazolin­
3­
one
breaks
down
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
1,2­
benzisothiazolin­
3­
one's
ready
biodegradation
in
soil
and
small
application
amount
greatly
reduce
the
exposure
potential
for
terrestrial
and
aquatic
organisms.
Run­
off
into
surface
water
from
pesticidal
uses
is
likely
to
be
low
and
it
is
not
likely
to
be
present
in
water
sources
at
substantial
concentrations.
Therefore,
risk
to
nontarget
organisms
is
not
anticipated
from
the
inert
uses
of
1,2­
benzisothiazolin­
3­
one.

Listed
Species:
The
indoor
uses
of
BIT
addressed
in
this
document
are
unlikely
to
result
in
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms,
and
thus
have
a
low
risk
potential
for
Listed
Species.
The
potential
exposure
to
terrestrial
and
aquatic
species
from
the
oil
recovery
uses
of
BIT
cannot
be
estimated
at
this
time,
as
there
is
currently
no
validated
model
available
for
such
a
purpose.
The
high
toxicity
of
BIT
to
green
algae
and
invertebrate
species
suggests
that
potential
adverse
acute
effects
could
occur
to
some
species
if
environmental
contamination
from
BIT­
treated
oil
recovery
fluids
occurs.
1,2­
benzisothiazolin­
3­
one
is
used
as
an
inert
ingredient
in
pesticide
products
but
the
allowable
amount
that
can
be
applied
is
small
(
not
more
than
0.1%
formulation
and
0.02
lbs.
per
acre).
Data
indicate
that
1,2­
benzisothiazolin­
3­
one
breaks
down
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
1,2­
benzisothiazolin­
3­
one's
ready
biodegradation
in
soil
and
small
application
amount
greatly
reduce
the
exposure
potential
for
terrestrial
and
aquatic
organisms.
Run­
off
into
surface
water
from
pesticidal
uses
is
likely
to
be
low
and
it
is
not
likely
to
be
present
in
water
sources
at
substantial
concentrations.
Therefore,
risk
to
Federally
listed
species
and
critical
habitats
is
not
likely
to
occur
from
the
inert
ingredient
uses
of
1,2­
benzisothiazolin­
3­
one.

Incident
Reports:
The
incident
reports
for
1,2­
benzisothiazolin­
3­
one
do
not
contain
information
that
would
be
of
concern.

Data
Gaps:
An
acute
inhalation
study
is
required
for
the
technical
grade
active
ingredient
based
on
new
waiver
criteria
and
advances
in
inhalation
technology
which
nullified
the
previous
waiver.
An
additional
developmental
study
may
be
required
to
remove
the
3X
database
uncertainty
factor
applied
to
oral
exposure
scenarios.

EPA
requires
that
the
registrant
submit
carcinogenicity
data
for
BIT
to
support
the
metal
working
fluid
use.
The
registrant
may
claim
that
a
carcinogenicity
study
would
not
be
required
for
the
metalworking
fluid
use
if
the
use
is
for
"
enclosed
metalworking
systems".
Under
this
scenario,
it
has
been
determined
that
certain
toxicology
data
requirements
including
carcinogenicity
testing
would
be
held
in
reserve
pending
review
of
worker
exposure
in
such
enclosed
systems.
9
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
2.1
Chemical
Identification
Chemical
identification
parameters,
including
chemical
and
common/
trade
names,
chemical
family,
CAS
Number,
and
molecular
formula
are
provided
in
Table
1.

Table
1.
Chemical
Identification
Parameter
Value
Chemical
Name
1,2­
benzisothiazolin­
3­
one
Common/
Trade
Names
IPX,
Proxan,
Proxel,
XBINX
®
,
Acticide
®
BIT
Chemical
Family
Isothiazolines
CAS
Number
2634­
33­
5
Molecular
Formula
C7H5NOS
2.2
Physical/
Chemical
Properties
The
physical
and
chemical
properties
of
the
Technical
Grade
Active
Ingredient
(
TGAI)
of
1,2­
benzisothiazolin­
3­
one
are
shown
in
Table
2.

Table
2.
Physical/
Chemical
Properties
Parameter
Value
Molecular
Weight
151.9
Color
Off
white
to
brown
Physical
State
solid
Specific
gravity
1.45
at
20oC
Dissociation
Constant
9.12
x
10­
8
pH
4.8
at
23oC
Stability
Stable
with
respect
to
sunlight
and
normal
or
elevated
temperatures;
not
stable
with
respect
to
copper
metal
and
iron
(
III)
ions
Melting
point
159.5­
160oC
Water
Solubility
Three
separate
solubilities
provided
by
different
registrants:
1118
ppm
at
20oC,
1380
ppm
at
24oC,
and
EPA
database
(
EPI
Suite)
lists
2.1
g/
L
at
25oC
Table
2.
Physical/
Chemical
Properties
Parameter
Value
10
Solubility
in
organic
solvents
°
methanol:
67,000
ppm
at
23oC
°
acetone:
42,000
ppm
at
24oC
°
dichloromethane:
31,000
ppm
at
23oC
°
toluene:
5,000
ppm
at
24oC
°
ethyl
acetate:
23,000
ppm
at
23oC
°
n­
hexane:
100
ppm
at
23oC
°
acetonitrile:
13,000
ppm
at
23oC
°
heptane:
135
ppm
at
20oC
Octanol­
water
Partition
Coefficient
20.0
at
25
°
C
Vapor
Pressurea
°
4.4
x
10­
7mm
Hg
at
20
°
C
°
9.8
x
10­
7mm
Hg
at
25
°
C
°
2.78
x
10­
6mm
Hg
at
25
°
C
Henry's
Law
Constant
°
2.38
x
10­
10
atm­
m3/
mole
Persistence
in
Air
Half­
life:
7.8
hours
a
Note:
a
number
of
registants
have
reported
various
values
for
the
vapor
pressure.
Since
these
values
are
within
experimental
errors,
the
Agency
does
not
consider
them
to
be
different
from
each
other
3.0
ENVIRONMENTAL
FATE
ASSESSMENT
The
environmental
fate
assessment
for
1,2­
benzisothiazolin­
3­
one
was
based
on
limited
information;
data
were
only
available
for
hydrolysis,
aerobic
soil
metabolism,
and
adsorption/
desorption.
These
data
indicate
that
1,2­
benzisothiazolin­
3­
one
is
hydrolytically
stable
(
half­
life
>
30
days),
but
breaks
down
fairly
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
1,2­
benzisothiazolin­
3­
one
shows
moderate
to
strong
binding
to
soils,
with
adsorption
K
d
values
estimated
to
be
between
1.24
to
9.56.
If
used
outdoors,
1,2­
benzisothiazolin­
3­
one
may
possibly
move
with
soil
during
rainfall
events
and
potentially
reach
surface
waters.
However,
it
breaks
down
aerobically
on
the
surface
soils.
Since
it
has
a
moderate
binding
potential
to
soils,
it
is
not
likely
to
migrate
into
the
ground
and
there
is
low
potential
for
ground
water
contamination.
Furthermore,
with
a
K
ow
value
of
20
at
25
o
C,
1,2­
benzisothiazolin­
3­
one
is
unlikely
to
bioaccumulate
in
aquatic
organisms.

4.0
HAZARD
CHARACTERIZATION
4.1
Hazard
Profile
A
detailed
hazard
assessment
for
1,2­
benzisothiazolin­
3­
one
is
presented
in
the
attached
appendix.

Acute
Toxicity.
Acute
toxicity
data
show
that
1,2­
benzisothiazolin­
3­
one
is
moderately
toxic
by
the
oral
and
dermal
routes
(
Toxicity
Category
III
for
both
studies),
but
that
this
chemical
is
a
severe
eye
irritant
(
Toxicity
Category
I).
Irritation
to
the
skin
from
acute
data
show
only
mild
11
skin
irritation
(
Toxicity
Category
IV),
but
repeated
dermal
application
indicated
a
more
significant
skin
irritation
response.
Table
3
presents
the
acute
toxicity
data
for
1,2­
benzisothiazolin­
3­
one
and
Table
4
highlights
the
key
toxicological
studies
for
1,2­
benzisothiazolin­
3­
one.

Subchronic
Toxicity.
Subchronic
oral
toxicity
studies
conducted
in
both
rats
and
dogs
showed
systemic
effects
after
repeated
oral
administration.
In
rats,
decreased
body
weight
was
observed
in
males
at
weeks
2,
3,
and
13
at
a
dose
of
69
mg/
kg/
day.
An
increased
incidence
of
forestomach
hyperplasia
was
also
observed
at
this
dose
level.
In
a
second
oral
gavage
study
in
rats,
non­
glandular
stomach
lesions
were
reported
in
both
sexes
at
doses
of
30
mg/
kg/
day
and
higher.
In
dogs,
the
effects
of
repeated
oral
dosing
of
1,2­
benzisothiazolin­
3­
one
occurred
at
lower
doses
than
in
rats,
and
included
alterations
in
blood
chemistry
(
decreased
plasma
albumin,
total
protein,
and
alanine
aminotransferase)
and
increased
absolute
liver
weight
at
a
dose
of
20
mg/
kg/
day.
A
90
day
dermal
toxicity
was
conducted
in
rats
and
although
the
study
was
classified
as
acceptable,
a
NOAEL
was
not
obtained
based
on
the
presence
of
stomach
lesions,
suggestive
of
oral
exposure
to
the
compound,
at
all
doses
tested
(
100,
300
and
1000
mg/
kg/
day).

Developmental
Toxicity.
Developmental
toxicity
studies
were
conducted
in
rats
with
1,2­
benzisothiazolin­
3­
one.
One
study
was
conducted
with
test
material
of
73.4%
purity,
and
maternal
effects
included
decreased
body
weight
gain
during
dosing
and
decreased
food
consumption,
both
occurring
at
a
dose
of
100
mg/
kg/
day.
The
other
study
was
conducted
with
test
material
of
100%
purity,
and
maternal
effects
in
this
study
consisted
of
clinical
toxicity
signs
(
audible
breathing,
haircoat
staining
of
the
anogenital
region,
dry
brown
material
around
the
nasal
area)
as
well
as
increased
mortality
at
a
dose
of
30
mg/
kg/
day.
In
both
studies,
however,
developmental
effects
were
similar
although
occurring
at
different
effect
levels,
and
consisted
of
increases
in
skeletal
abnormalities
(
extra
sites
of
ossification
of
skull
bones,
unossified
sternebra)
but
not
external
or
visceral
abnormalities.
Despite
the
differences
in
purity
of
the
test
material
in
the
two
studies,
the
effect
levels
at
which
fetal
effects
occurred
were
similar
in
both
studies
(
100mg/
kg
and
90g/
kg
for
the
first
and
second
studies,
respectively).

Reproductive
Toxicity.
A
two­
generation
reproduction
study
was
conducted
in
which
1,2­
benzisothiazolin­
3­
one
was
administered
in
the
diet
at
concentrations
of
0,
250,
500
or
1000
ppm.
Parental
toxicity
was
observed
at
500
ppm
and
was
characterized
by
lesions
in
the
stomach.
In
pups,
toxic
effects
were
reported
at
1000
ppm
and
consisted
of
preputial
separation
in
males
and
impaired
growth
and
survival
in
both
sexes.
The
reproduction
study
did
not
show
evidence
of
increased
susceptibility
of
offspring
to
the
effects
of
1,2­
benzisothiazolin­
3­
one.

Dermal
Penetration.
A
dermal
penetration
study
was
conducted
in
rats
in
which
a
10
mg/
kg
dermal
dose
of
1,2­
benzisothiazolin­
3­
one
was
applied
to
the
skin
for
durations
of
4,
8,
24,
48
or
72
hours.
At
72
hours
a
maximum
dermal
penetration
of
40.6%
was
achieved.

Mutagenicity.
Acceptable
mutagenicity
studies
were
conducted
with
1,2­
benzisothiazolin­
3­
one
which
evaluated
both
point
mutations
(
mouse
lymphoma
test),
micronucleus
formation,
and
unscheduled
DNA
synthesis.
All
acceptable
studies
conducted
showed
a
negative
mutagenic
response
for
this
chemical.
In
an
unacceptable
Ames
test,
one
strain
of
bacteria
(
TA102)
had
a
positive
mutagenic
response,
with
mammalian
metabolic
activation,
in
12
three
separate
experiments.
The
test
was
deemed
unacceptable
due
to
failure
to
report
test
material
purity.

Metabolism.
Metabolism
studies
show
that
91%
of
the
test
material
was
excreted
in
the
urine.
Accumulation
was
not
reported
in
the
abdominal
fat
and
#
0.22
ppm
1,2­
benzisothiazolin­
3­
one
was
recovered
from
the
liver
tissue
samples.
There
were
no
metabolites
of
toxicological
concern.

Neurotoxicity.
The
ADTC
concluded
that
there
is
not
a
concern
for
neurotoxicity
resulting
from
exposure
to
1,2­
benzisothiazolin­
3­
one.
The
neurotoxicity
observed
in
the
rat
acute
oral
toxicity
study
(
piloerection
and
upward
curvature
of
the
spine
at
300
mg/
kg
and
above;
decreased
activity,
prostration,
decreased
abdominal
muscle
tone,
reduced
righting
reflex,
and
decreased
rate
and
depth
of
breathing
at
900
mg/
kg)
and
the
acute
dermal
toxicity
study
(
upward
curvature
of
the
spine
was
observed
in
increased
incidence,
but
this
was
absent
after
day
5
postdose
at
a
dose
of
2000
mg/
kg)
were
felt
to
be
at
exposures
in
excess
of
those
expected
from
the
use
pattern
of
this
pesticide
and
that
such
effects
would
not
be
observed
at
estimated
exposure
doses.

Table
3.
Acute
Toxicity
of
1,2­
benzisothiazolin­
3­
one
Guideline
No.
Study
Type
MRID
#(
s)
Results
Toxicity
Category
870.1100
Acute
Oral
41022101;
42858101
LD50
=
670
mg/
kg
(
M);
784
mg/
kg
(
F)
III
870.1200
Acute
Dermal
41022102;
42858102
LD50
>
2000
mg/
kg
III
870.1300
Acute
Inhalation
waiver
granted
870.2400
Primary
Eye
Irritation
42905102
severe
eye
irritant
I
870.2500
Primary
Skin
Irritation
42905101
slight
irritant
IV
870.2600
Dermal
Sensitization
41750001;
42858103
moderate
dermal
sensitizer
Not
Applicable
Table
4.
Toxicity
Profile
of
1,2­
benzisothiazolin­
3­
one
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
870.3100
90­
Day
oral
toxicity
rodents
41910401
(
1990)
satisfies
guideline
0,
200,
900,
4000
ppm
M:
0,
15.3,
69.0,
322
mg/
kg/
d
F:
0,
17.6,
78.3,
356
mg/
kg/
d
NOAEL
=
15.3
(
male)
and
78
mg/
kg/
day
(
female)
LOAEL
=
69
(
male)
and
356
mg/
kg/
day
(
female)
based
on
decreased
body
weights
in
both
males
and
females
and
increased
incidence
of
gross
non­
neoplastic
lesions
in
females.
Table
4.
Toxicity
Profile
of
1,2­
benzisothiazolin­
3­
one
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
13
870.3100
90­
Day
oral
toxicity
rodents
46346201
(
2002)
satisfies
guideline
0,10,30,
75
mg/
kg/
d
NOAEL
=
10
mg/
kg/
d
LOAEL
=
30
mg/
kg/
d
based
on
gross
and
microscopic
lesions
in
the
stomach
of
both
sexes
870.3150
90­
Day
oral
toxicity
in
nonrodents
42205701
(
1991)
0,
5,
20,
and
50
mg/
kg/
day
NOAEL
=
5
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
the
incidence
of
emesis
and
clinical
chemistry
alterations.

870.3250
90­
Day
dermal
toxicity
45184601
(
1998)
acceptable/
guideline
0,
100,
300,
1000
mg/
kg
Systemic
NOAEL
$
1000
mg/
kg/
day
Non­
systemic
LOAEL
<
100
mg/
kg/
day
based
on
stomach
pathology,
indicative
of
irritation.

870.3700a
Prenatal
developmental
in
rodents
43663008
(
1994)
0,
10,
30,
and
90
mg/
kg/
day
40961201/
42858104
(
1988/
1993)
0,
10,
40,
and
100
mg/
kg/
day
Maternal
NOAEL
=
10
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day
based
on
mortality,
clinical
signs
of
toxicity,
and
gross
pathology
findings.
Developmental
NOAEL
=
30
mg/
kg/
day
LOAEL
=
90
mg/
kg/
day
based
on
treatment­
related
increase
in
litter
and
fetal
incidence
of
extra
sites
of
ossification
of
the
skull
bones
and
unossified
sternebra.

Maternal
NOAEL
=
40
mg/
kg/
day
LOAEL
=
100
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption.
Developmental
NOAEL
=
40
mg/
kg/
day
LOAEL
=
100
mg/
kg/
day
based
on
decreased
fetal
body
weight
and
increased
incidence
of
delays
in
skeletal
ossification..

870.3800
Reproductive
toxicity
Rodents
46097101
(
2002)
0,
250,
500,
1000
ppm
M:
24,
48,
98
mg/
kg/
day
(
approximate
dose)
Parental
NOAEL=
250
ppm
Parental
LOAEL
=
500
ppm
based
on
hyperplasia
of
the
limiting
ridge
of
the
stomach
Offspring
NOAEL
=
500
ppm
Offspring
LOAEL
=
1000ppm
based
on
preputial
separation
in
F1
males
and
impaired
growth
and
survival
of
pups
in
both
sexes.

870.7600
Dermal
Penetration
Rodents
46237901
(
1999)
dermal
dose
:
10
mg/
kg
acceptable/
non­
guideline
Approximately
41%
dermal
penetration
(
maximum)
was
reported
after
72
hours
Table
4.
Toxicity
Profile
of
1,2­
benzisothiazolin­
3­
one
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification/
Doses
Results
14
Gene
Mutation
870.5100
Microbial
gene
mutation
assay
870.5300
In
vitro
mammalian
cell
gene
mutation
test
45534603
(
1996)
classification:
unacceptable­
guideline
0.07,
0.33,
1.64,
8.2,
and
41
µ
g/
plate,
±
S9,
first
test
0.07,
0.33,
1.64,
8.2,
and
41
µ
g/
plate
­
S9,
and
0.41,
0.82,
4.1,
8.2,
20.5,
and
57.4
µ
g/
plate
+
S9,
second
test
41022103/
42858105
(
1988/
1993)
classification:
coreacceptable
0.03
to
2.00
µ
g/
mL
(­
S9)
1
to
64
µ
g/
mL
(+
S9)
In
strain
TA102,
there
was
evidence
of
a
positive
mutagenic
response,
+
S9,
in
three
separate
experiments.
No
other
strains
showed
evidence
of
positive
mutagenicity
in
this
assay.

No
biologically
significant
increase
in
mutation
frequency
was
noted
at
the
thymidine
kinase
locus
either
with
or
without
metabolic
activation
at
any
of
the
concentrations
tested.

Cytogenetics
870.5393
Mouse
micronucleus
assay
41022104/
42858106
(
1988/
1993)
classification:
coreacceptable
245
or
392
mg/
kg
(
males),
331
or
529
mg/
kg
(
females)
No
significant
increases
in
the
frequency
of
micronucleated
polychromatic
erythrocytes
were
noted
in
the
bone
marrow
at
any
of
the
times
tested.

Other
Genotoxicity
870.870.5550
unscheduled
DNA
synthesis
assay
in
primary
rat
hepatocytes
41022105/
42858107
(
1988/
1993)
classification:
acceptable
10­
8
to
10­
5
M
The
test
compound
did
not
induce
unscheduled
DNA
synthesis
in
primary
cultures
of
rat
hepatocytes.

870.7485
Metabolism
and
pharmacokinetics
45124901
(
1972)
acceptable/
guideline
single
20
mg/
kg
dose
or
2,3,
or
4
daily
doses
of
10
mg/
kg
The
results
reported
were
based
on
the
analysis
of
urine
and
fecal
samples
collected
from
the
rats
in
Group
1
and
abdominal
fat
and
liver
samples
from
the
rats
in
Group
2.
The
estimated
percentage
of
radioactivity
in
the
excreta
was
reported
for
individual
animals
every
24
hours
for
3
days
(
feces)
or
5
days
(
urine).
The
authors
report
that
in
Group
1,
91%
of
the
radioactivity
was
excreted
in
the
urine
within
5
days
post
exposure
and
5%
was
excreted
in
the
feces.
In
the
Group
2
rats,
accumulation
was
not
reported
in
the
abdominal
fat
and
#
0.22
ppm
BIT
was
recovered
from
the
liver
tissue
samples.
15
4.2
FQPA
Considerations
Under
the
Food
Quality
Protection
Act
(
FQPA),
P.
L.
104­
170,
which
was
promulgated
in
1996
as
an
amendment
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
was
directed
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children"
from
aggregate
exposure
to
a
pesticide
chemical
residue.
The
law
further
states
that
in
the
case
of
threshold
effects,
for
purposes
of
providing
this
reasonable
certainty
of
no
harm,
"
an
additional
tenfold
margin
of
safety
for
the
pesticide
chemical
residue
and
other
sources
of
exposure
shall
be
applied
for
infants
and
children
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
data
with
respect
to
exposure
and
toxicity
to
infants
and
children.
Notwithstanding
such
requirement
for
an
additional
margin
of
safety,
the
Administrator
may
use
a
different
margin
of
safety
for
the
pesticide
residue
only
if,
on
the
basis
of
reliable
data,
such
margin
will
be
safe
for
infants
and
children."

On
August
28,
2002
the
Antimicrobials
Division's
Toxicology
Endpoint
Selection
Committee
(
ADTC)
reviewed
the
available
toxicology
data
for
1,2­
benzisothiazolin­
3­
one
(
BIT)
with
regard
to
the
acute
and
chronic
Reference
Doses
(
RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
1,2­
benzisothiazolin­
3­
one
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.
On
February
8,
2005,
the
ADTC
met
again
to
consider
additional
data
submitted
by
the
registrant
in
response
to
the
conclusions
reached
from
the
first
meeting
and
as
discussed
in
the
September
2002
ADTC
memo.
The
ADTC
recommended
that
the
special
hazard­
based
FQPA
safety
factor
of
10x
be
reduced
to
1x.
The
reduction
of
the
safety
factor
from
10x
to
1x
is
based
on
submission
of
the
2­
generation
reproduction
toxicity
study
which
was
previously
cited
as
a
data
gap
and
the
lack
of
evidence
for
susceptibility
in
this
study.
Taken
together
with
the
already
reviewed
developmental
toxicity
data
that
showed
no
evidence
of
susceptibility,
the
ADTC
concluded
the
special
FQPA
hazard­
based
factor
could
be
reduced
to
1x.
Also,
use
of
NOAEL
values
from
the
subchronic
toxicity
studies
in
the
dog
and
rat
for
the
dietary
endpoints
are
protective
as
these
values
(
5
mg/
kg/
day
and
8.42
mg/
kg/
day)
are
lower
than
the
NOAEL
values
from
the
developmental
studies
(
10
and
40
mg/
kg/
day
respectively).
However
a
3X
database
uncertainty
factor
was
retained
for
use
in
oral
exposure
scenarios
based
on
uncertainties
in
the
existing
developmental
toxicity
database
(
specifically
in
the
maternal
toxicity)
and
the
lack
of
developmental
toxicity
data
in
non­
rodents.
16
4.3
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
by
ADTC
for
various
exposure
scenarios
are
summarized
in
Table
5
below.

Table
5.
Summary
of
Toxicology
Endpoints
Selected
for
1,2­
benzisothiazolin­
3­
one
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOE,
UF,
Special
FQPA
SF,
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
General
population,
including
infants
and
children
NOAEL=
5
mg/
kg/
day
UF
=
100
(
10x
inter­
species
extrapolation,
10x
intra­
species
variation)
FQPA
SF=
1
DB
UF
=
3
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
non­
glandular
and
glandular
regions
of
the
stomach.

Chronic
Dietary
All
populations
NOAEL=
5
mg/
kg/
day
UF
=
100
(
10x
inter­
species
extrapolation,
10x
intra­
species
variation)
FQPA
SF=
1
DB
UF
=
3
Chronic
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
non­
glandular
and
glandular
regions
of
the
stomach.

Non­
Dietary
Risk
Assessments
Incidental
Oral
(
short
and
intermediate
term
NOAEL=
5
mg/
kg/
day
MOE
=
300
(
10x
interspecies
extrapolation,
10x
intraspecies
variation)
FQPA
SF=
1
DB
UF=
3
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
non­
glandular
and
glandular
regions
of
the
stomach.
Table
5.
Summary
of
Toxicology
Endpoints
Selected
for
1,2­
benzisothiazolin­
3­
one
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOE,
UF,
Special
FQPA
SF,
for
Risk
Assessment
Study
and
Toxicological
Effects
17
Dermal
All
time
periods
(
occupational
and
residential)
NOAEL=
5
mg/
kg/
day
MOE
=
100
(
10x
interspecies
extrapolation,
10x
intraspecies
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
non­
glandular
and
glandular
regions
of
the
stomach.

Inhalation
All
time
periods
(
occupational
and
residential)
NOAEL=
5
mg/
kg/
day
MOE
=
100
(
10x
inter­
species
extrapolation,
10x
intraspecies
variation)

An
additional
10x
route­
toroute
extrapolation
is
used
to
determine
if
an
inhalation
toxicity
study
is
warranted.
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
non­
glandular
and
glandular
regions
of
the
stomach.

Cancer
No
cancer
data
available
for
1,2­
benzisothiazolin­
3­
one
Notes:
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
DB
UF
=
data
base
uncertainty
factor,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
LOC
=
level
of
concern,
MOE
=
margin
of
exposure
4.4
Endocrine
Disruption
The
Food
Quality
Protection
Act
(
FQPA;
1996)
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticides
and
inerts)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect...."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).
18
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
1,2­
benzisothiazolin­
3­
one
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
5.1
Summary
of
Registered
Uses
1,2­
benzisothiazolin­
3­
one,
a
member
of
the
Isothiazoline
class,
is
an
industrial
preservative
that
is
recommended
to
inhibit
the
control
the
growth
of
microorganisms
in
the
preserved
product.
1,2­
benzisothiazolin­
3­
one
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,
metalworking
fluids,
casein/
rosin
dispersions,
textile
spin­
finish
solutions,
laundry
detergents,
pesticide
formulations,
tape
joint
compound,
leather
processing
solutions,
preservation
of
fresh
animal
hides
and
skins,
and
for
offshore
and
terrestrial
gas/
oil
drilling
muds
and
packer
fluids
preservation.
Furthermore,
1,2­
benzisothiazolin­
3­
one
is
used
as
an
inert
ingredient
in
over
900
different
products
primarily
as
a
materials
preservative.
The
specific
antimicrobial
use
categories
include
the
following
general
use
patterns:
material
preservatives
(
indoor
food
and
indoor/
outdoor
non­
food),
industrial
processes
and
water
systems
(
indoor
nonfood),
and
indoor
and
outdoor
residential
uses.

5.2
Dietary
Exposure
for
Active
Ingredient
Uses
The
Agency
has
carried
out
the
dietary
exposure
and
risk
assessment
for
use
of
1,2­
benzisothiazolin­
3­
one
as
a
pulp
and
paper
slimicide,
and
a
preservative
in
paper
coatings
and
paper
adhesives,
all
of
which
may
result
in
indirect
food
contact
exposures.
No
residue
chemistry
data
were
submitted
by
the
registrants,
nor
were
any
asked
for
by
the
Agency.
The
Agency
has
used
the
US
FDA
methodology
to
estimate
1,2­
benzisothiazolin­
3­
one
residues
on
food
due
to
migration
of
this
chemical
from
food­
contact
paper
to
food
(
US
FDA,
2002).
The
FDA
methodology
makes
the
following
basic
assumptions
to
calculate
the
Estimated
Daily
Intake
(
EDI):

°
Food
contact
surface
could
be
a
one
time
use/
day
or
repeat
use
material/
day;
°
The
amount
of
food
that
comes
into
contact
with
the
treated
paper
is
based
on
an
FDA
default
value;
and
°
All
of
the
active
material
present
in
the
paper
migrates
into
the
food.

Additionally,
based
on
the
Label
67071­
24
(
Acticide
BW10),
the
amount
of
1,2­
benzisothiazolin­
3­
one
used
as
a
slimicide
and
as
a
preservative
in
paper
coating
and
paper
adhesive
is
5
lbs
of
product
per
1,000
pounds
of
material
being
preserved.
The
concentration
of
1,2­
benzisothiazolin­
3­
one
in
Acticide
BW10
is
10%.
19
5.2.1
Residue
Profile
There
are
no
known
residues
of
concern
for
1,2­
benzisothiazolin­
3­
one.

5.2.2
Acute
Dietary
The
acute
dietary
risks
for
adults
and
children
are
discussed
in
5.2.3.

5.2.3
Chronic
Dietary
The
acute
and
chronic
dietary
risks
for
adult
and
children
from
exposure
to
treated
paper
are
shown
in
Table
6.
For
adults,
the
cumulative
acute
and
chronic
dietary
exposure
is
9.4%
of
the
acute
PAD
and
chronic
PAD.
For
children,
the
cumulative
acute
and
chronic
dietary
exposure
is
21.8%
of
the
acute
PAD
and
chronic
PAD.
The
highest
exposure
is
for
the
children.

Table
6.
Summary
of
Dietary
Exposure
and
Risk
for
1,2­
Benzisothiazolin­
3­
one
Population
Subgroup
EDI
(:
g/
person/
day)
Acute
and
Chronic
Dietary
Dietary
Exposurea
(
mg/
kg/
day)
%
aPAD
and
%
cPAD
b
Slimicide
Adult
14.1
0.0002
1.2
Child
7.05
0.00047
2.8
Paper
Adhesive
Preservative
Adult
21.0
0.0003
1.8
Child
10.5
0.0007
4.1
Paper
Coating
Preservative
Adult
75.0
0.0011
6.5
Child
37.5
0.0025
14.7
Cumulative
Adult
110.1
0.0016
9.4
Child
55.1
0.0037
21.8
a­­
For
adults,
acute
and
chronic
exposure
analysis
is
based
on
a
body
weight
of
70
kg.
For
children,
exposure
is
based
on
a
body
weight
of
15
kg.
b­­%
PAD
=
dietary
exposure
(
mg/
kg/
day)
*
100
/
aPAD
or
cPAD,
where
aPAD
and
cPAD
for
adults
and
children
=
0.017
mg/
kg/
day
20
5.2.4
Cancer
Dietary
There
are
no
dietary
cancer
risks
identified
for
1,2­
benzisothiazolin­
3­
one.

5.3
Dietary
Exposure
for
Inert
Ingredient
Uses
Included
in
this
RA
is
the
reassessment
of
1,2­
benzisothiazolin­
3­
one
when
used
as
an
inert
ingredient
in
pesticide
products.
1,2­
benzisothiazolin­
3­
one
is
used
as
a
preservative/
stabilizer
in
a
wide
variety
of
residential
use
and
agricultural
pesticide
products,
including
outdoor
yard,
garden,
and
turf
products,
and
agricultural
crop
products.
1,2­
benzisothiazolin­
3­
one
currently
has
one
inert
ingredient
exemption
from
the
requirement
of
a
tolerance
for
residues
as
required
under
the
Food
Quality
Protection
Act
(
FQPA)
section
408.
The
existing
exemption
is
for
use
on
growing
crops
under
40
CFR
part
180.920.
In
addition,
the
Agency
has
received
a
petition
to
establish
an
exemption
from
the
requirement
for
a
tolerance
for
the
use
of
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient
in
pesticides
applied
to
animals
under
40
CFR
part
180.930.
The
existing
exemption
from
the
requirement
of
a
tolerance
as
well
as
the
proposed
exemption
are
summarized
in
Table
7.

Table
7.
Tolerance
Exemptions
Tolerance
Exemption
Expression
CAS
Number
40
CFR
§
Limits
Use
1,2­
benzisothiazolin­
3­
one
(
Also
known
as
"
BIT")
2634­
33­
5
180.9201
180.9302
Not
more
than
0.1%
of
formulation.
Not
more
than
0.02
lbs.
to
be
applied
per
acre.
preservative/
stabilizer
1.
Residues
listed
in
40
CFR
§
180.920
are
exempted
from
the
requirement
of
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
when
applied
to
growing
crops
only.

2.
Residues
listed
in
40
CFR
§
180.930
are
exempted
from
the
requirement
of
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
when
applied
to
animals
only.

Inert
Dietary
Exposure
Assumptions
A
dietary
exposure
analysis
for
the
inert
ingredient
use
of
1,2­
benzisothiazolin­
3­
one
was
conducted
using
the
generic
screening
model
for
estimating
inert
ingredient
dietary
exposure
as
a
basis
for
estimating
1,2­
benzisothiazolin­
3­
one
dietary
exposure.
The
generic
model's
output
was
adjusted
to
reflect
the
tolerance
exemption
limitation
given
in
40
CFR
§
180.920
which
states
that
1,2­
benzisothiazolin­
3­
one
cannot
be
applied
at
more
than
0.02
lbs
per
acre.
The
generic
screening
model
does
not
specifically
include
an
application
rate
input,
rather
it
is
based
on
tolerances
for
pesticide
active
ingredients
with
application
rates
generally
ranging
from
1
to
5
lb
21
ai/
acre.
Therefore,
to
more
accurately
estimate
residues
resulting
from
the
lower
application
rate
limitation
of
0.02
lbs/
acre
of
1,2­
benzisothiazolin­
3­
one,
the
results
from
the
generic
model
were
adjusted
by
a
factor
of
50
(
using
the
ratio
of
1
lb.
per
acre
÷
0.02
lbs
per
acre)
and
250
(
using
the
ratio
of
5
lbs.
per
acre
÷
0.02
lbs/
acre)
to
reflect
residue
levels
resulting
from
the
specified
maximum
application
rate
of
1,2­
benzisothiazolin­
3­
one.

The
dietary
assessment
is
unrefined
and
extremely
conservative
in
nature
because
the
screening
model
assumes
that
the
inert
ingredient
is
used
on
all
commodities,
and
that
100
percent
of
crops
are
treated
with
the
inert
ingredient.
Further,
the
model
assumes
residues
will
be
present
for
every
consumed
commodity
(
including
meat,
milk,
poultry
and
eggs)
that
is
included
in
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
)
.
Additionally,
in
the
case
of
1,2­
benzisothiazolin­
3­
one,
the
choice
of
an
adjustment
factor
based
on
maximum
application
rate
is
conservative
in
nature,
because
the
use
of
an
adjustment
factor
based
on
concentration
in
formulation
results
in
exposures
less
than
half
of
the
lowest
values
for
the
U.
S.
population
and
all
population
subgroups
reported
in
Tables
8
and
9.

Inert
Dietary
Risk
from
Food
The
tables
below
provide
a
summary
of
the
results
of
the
acute
and
chronic
dietary
risk
estimates
for
1,2­
benzisothiazolin­
3­
one.
Only
one
population
subgroup
had
an
estimated
exposure
over
100
%
of
either
PADs
at
the
95th
percentile
of
exposure
 
"
Children
(
1­
2
years)"
had
112%
of
the
aPAD
but
this
was
only
at
the
high
end
of
exposure.
Considering
the
unrefined
and
extremely
conservative
nature
of
this
screening
level
model
(
e.
g.,
inclusion
of
all
commodities;
100%
of
commodities
are
treated;
adjustment
factor
for
application
rate),
the
results
for
all
population
subgroups
are
considered
not
to
be
of
concern.

It
should
be
noted
that
while
the
results
from
the
screening
level
model
do
not
raise
a
dietary
concern,
the
modeling
results
would
be
even
lower
if
an
alternate
adjustment
factor
had
been
used.
As
described
in
the
"
Exposure
Assumptions"
section
above,
1,2­
benzisothiazolin­
3­
one's
maximum
application
rate
of
0.02
lbs/
acre
was
adjusted
by
50
and
250
in
the
generic
model.
Instead
of
adjusting
for
application
rate,
the
model
could
have
been
adjusted
for
the
concentration
of
1,2­
benzisothiazolin­
3­
one
in
the
pesticide
formulation,
which
is
limited
to
a
maximum
of
0.1%
under
40
CFR
§
180.920
(
the
proposed
tolerance
exemption
for
use
on
animals
under
180.930
has
the
same
limitation).
Adjusting
the
model
for
the
concentration
in
the
formulation
would
mean
using
a
factor
of
500.

The
adjustment
factor
using
formulation
concentration
is
500,
which
is
calculated
using
1,2­
benzisothiazolin­
3­
one's
maximum
concentration
(
0.1%)
and
a
value
used
in
the
screen
level
model
of
50%,
which
represents
a
group
of
active
ingredients
that
are
typically
found
in
agricultural
food
use
products
at
concentrations
>
50%.
Using
the
adjustment
factor
of
500
(
50%
÷
0.1%)
to
account
for
the
effect
of
the
limitation
of
0.1%
of
1,2­
benzisothiazolin­
3­
one
in
pesticide
formulations
on
residue
levels
would
certainly
lower
the
model
results
even
further
that
what
are
presented
in
the
Tables
8
and
9,
below.
22
This
dietary
assessment
includes
the
existing
use
of
1,2­
benzisothiazolin­
3­
one
as
a
pesticide
inert
ingredient
used
on
growing
crops
under
40
CFR
part
180.920.
In
addition,
the
Agency
has
received
a
petition
to
establish
an
exemption
from
the
requirement
for
a
tolerance
for
the
use
of
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient
in
pesticides
applied
to
animals
under
40
CFR
part
180.930
with
the
same
limitations
as
currently
exist
under
180.920.
This
dietary
assessment
also
includes
animals
as
a
commodity.
Therefore,
the
results
of
this
assessment
cover
all
existing
and
currently
proposed
inert
ingredient
uses
of
1,2­
benzisothiazolin­
3­
one.
Dietary
exposures
of
concern
from
food
are
not
likely
from
the
use
of
1,2­
benzisothiazolin­
3­
one
as
inert
ingredients
in
pesticide
products.

Table
8.
Estimated
Acute
Dietary
(
Food)
Risk
Estimates
for
1,2­
benzisothiazolin­
3­
one
Population
Subgroup
95th
Percentile
of
Exposure
BIT
Estimated
Exposure,
mg/
kg/
day
%
aPAD1/

U.
S.
Population
(
total)
0.0013
­
0.007
8%
­
40%

All
infants
(<
1
year)
0.0028
­
0.014
17%
­
84%

Children
(
1­
2
years)
0.0038
­
0.019
22%
­
112%

Children
(
3­
5
years)
0.0027
­
0.014
16%
­
82%

Children
(
6­
12
years)
0.0016
­
0.008
9%
­
47%

Youth
(
13­
19
years)
0.0010
­
0.005
6%
­
29%

Adults
(
20­
49
years)
0.00080
­
0.004
5%
­
24%

Adults
(
50+
years)
0.00076
­
0.004
5%
­
23%

Females
(
13­
49
years)
0.00079
­
0.004
5%
­
24%

1/
aPAD=
0.017
mg/
kg/
day
23
Table
9.
Chronic
Dietary
(
Food)
Risk
Estimates
for
1,2­
benzisothiazolin­
3­
one
Population
Subgroup
BIT
Estimated
Exposure,
mg/
kg/
day
%
cPAD2/

U.
S.
Population
(
total)
0.00048
­
0.0024
3%
­
14%

All
infants
(<
1
year)
0.0010
­
0.0049
6%
­
29%

Children
(
1­
2
years)
0.0017
­
0.0084
10%
­
51%

Children
(
3­
5
years)
0.0012
­
0.0062
7%
­
37%

Children
(
6­
12
years)
0.00070
­
0.0035
4%
­
21%

Youth
(
13­
19
years)
0.00040
­
0.0020
2%
­
12%

Adults
(
20­
49
years)
0.00035
­
0.0017
2%
­
10%

Adults
(
50+
years)
0.00034
­
0.0017
2%
­
10%

Females
(
13­
49
years)
0.00035
­
0.0017
2%
­
10%

2/
cPAD=
0.017
mg/
kg/
day
5.4
Drinking
Water
Exposures
and
Risks
Based
on
environmental
fate
data,
1,2­
benzisothiazolin­
3­
one
binds
moderately
with
soil
and
may
potentially
move
with
the
soil
during
rainfall
events
and
reach
surface
waters.
Although,
1,2­
benzisothiazolin­
3­
one
has
been
shown
to
be
hydrolytically
stable
with
a
half
life
of
>
30
days,
it
breaks
down
fairly
quickly
in
aerobic
soils.
Outdoor
use
patterns
of
1,2­
benzisothiazolin­
3­
one
which
may
lead
to
contact
with
soil
and/
or
surface
water
include:
1)
the
application
of
agricultural
pesticides
that
contain
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient,
and
2)
the
application
of
paints
that
contain
1,2­
benzisothiazolin­
3­
one.
Considering
1,2­
benzisothiazolin­
3­
one's
ready
biodegradation
and
the
small
amount
of
(
0.02
lbs.
per
acre)
that
may
be
applied
to
crops
via
the
inert
use
and
the
small
amount
likely
to
come
into
contact
with
soils/
surface
waters
via
the
paint
use,
1,2­
benzisothiazolin­
3­
one
is
not
likely
to
be
present
in
food
or
drinking
water
sources
at
substantial
concentrations.
Therefore
a
quantitative
drinking
water
assessment
was
not
conducted.
24
5.5
Residential
Exposures
and
Risks
for
Active
Ingredient
Uses
A
detailed
human
exposure
risk
assessment
for
1,2­
benzisothiazolin­
3­
one
is
provided
in
the
attached
Appendix.
The
summary
of
the
exposures
and
risks
to
the
residential
population
are
presented
below.

5.5.1
Residential
Handler
Scenarios
1,2­
benzisothiazolin­
3­
one
may
be
added
to
residential­
use
products
used
to
control
bacteria
and
fungi,
including
as
a
preservative
for
paint
(
e.
g.,
EPA
Reg.
No.
72674­
15)
and
household
cleaning
products.
The
residential
handler
scenarios
evaluated
including
handling
BITcontaining
paint
through
brush/
roller
and
airless
spray
application
methods
and
handling
BITcontaining
cleaning
products
through
low­
pressure
spray,
wiping,
and
mopping
application
methods.
Where
the
data
were
available,
residential
assessment
assumed
that
the
handlers
would
be
wearing
short­
pants
and
short­
sleeved
shirts.
For
example,
the
data
available
in
the
Pesticide
Handlers
Exposure
Database
(
PHED)
provides
unit
exposures
for
both
a
short
pant/
sleeve
scenario
as
well
as
a
long
pant/
sleeve
scenario
(
explaining
the
difference
between
the
residential
unit
exposures
and
the
occupational
unit
exposures
for
painters).

5.5.1.1
Paint
Exposures
and
Risks
There
are
no
chemical­
specific
exposure
data
to
assess
paint
applications.
Therefore,
dermal
and
inhalation
exposures
were
assessed
for
brush
and
airless
sprayer
applications
using
surrogate
data.
Specifically,
PHED
Version
1.1
values
found
in
the
Residential
Exposure
SOPs
(
U.
S.
EPA,
1997a)
were
used
(
short
pants,
short­
sleeved
shirts).
The
surrogate
exposure
data
in
PHED
are
based
on
test
subjects
painting
a
bathroom
with
a
paint
brush
and
staining
the
outside
of
a
house
with
an
airless
sprayer.
The
dermal
and
inhalation
exposures
from
these
techniques
have
been
normalized
by
the
amount
of
active
ingredient
handled
and
reported
as
unit
exposures
(
UE)
expressed
as
mg/
lb
ai
handled.
In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
residential
handler
exposures.
Specifically,
it
was
assumed
that
residential
handlers
will
use
2
gallon/
day
(
20
lbs/
day)
of
paint
for
brush
applications
and
15
gallons/
day
(
150
lbs/
day)
of
paint
for
airless
sprayer
applications.
Additionally,
based
on
the
label
for
EPA
Registration
No.
67071­
24,
5
lbs
of
the
formulated
material
preservative
(
10%
a.
i.)
are
used
per
1,000
lb
of
paint.
Therefore,
the
use
amount
for
paint
brush
applications
is
0.01
lb
ai/
day
(
20
lbs
paint/
day
x
(
5
lb
product/
1000
lb
paint)
x
10%
ai)
and
the
use
amount
for
airless
sprayer
applications
is
0.075
lb
ai/
day
(
150
lbs
paint/
day
x
(
5
lb
product/
1000
lb
paint)
x
10%
ai).
All
homeowner
painting
scenarios
are
believed
to
be
best
represented
by
the
short­
term
exposure
duration.

The
non­
cancer
risk
estimates
are
expressed
in
terms
of
margin
of
exposure
(
MOE).
MOEs
greater
than
100
for
inhalation
and
dermal
exposures
do
not
exceed
the
Agency's
level
of
concern
for
residents
(
i.
e.,
"
target"
MOEs).
For
the
paint
scenarios,
the
short­
term
dermal
MOE
for
the
paint
brush/
roller
use
is
370
and
for
the
airless
sprayer
140.
Thus,
the
dermal
MOEs
are
not
of
concern
for
painting.
The
short­
term
inhalation
MOE
is
130,000
and
5,600
for
the
brush/
roller
and
airless
sprayer,
respectively.
Therefore,
the
inhalation
exposure
indicates
that
the
25
risks
do
not
exceed
the
Agency's
level
of
concern.
The
total
risk
(
inhalation
+
dermal)
is
also
presented
because
both
toxicological
endpoints
are
from
the
same
study
(
and
same
toxicological
effect).
The
total
MOEs
for
the
brush/
roller
and
airless
sprayer
are
370
and
140,
respectively.
The
dose
and
MOEs
are
summarized
in
Table
10.

5.5.1.2
Cleaning
Product
Exposures
and
Risks
The
following
two
scenarios
were
considered
for
residential
handlers
of
BIT­
containing
cleaning
products:

°
Use
of
cleaner
as
a
wipe
on
hard
non­
porous
surfaces,
and
°
Use
of
cleaner
for
mopping
hard
non­
porous
surfaces
such
as
floors.

These
potential
exposures
from
a
general
purpose
cleaner
are
expected
to
be
best
represented
by
the
short­
term
duration.
The
short­
term
dermal
and
inhalation
exposures
were
assessed
for
wipe
and
mopping
application
methods
using
surrogate
data.
Specifically,
values
from
the
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
study
(
U.
S.
EPA,
1999)
were
used.
The
dermal
and
inhalation
exposures
from
these
techniques
have
been
normalized
by
the
amount
of
active
ingredient
handled
and
reported
as
unit
exposures
(
UE)
expressed
as
mg/
lb
ai
handled.
In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
residential
handler
exposures.
Specifically,
it
was
assumed
that
residential
handlers
will
use
0.5
liters
of
cleaning
solution
wiping
and
1
gallon
of
cleaning
solution
for
mopping.
Additionally,
based
on
the
label
for
EPA
Registration
No.
67071­
22,
it
is
assumed
that
0.000033
lb
ai
are
used
for
wiping
(
i.
e.,
0.13
gal
solution
x
8.3
lb/
gal
density
x
0.15
lb/
1000
lb
cleaning
solution
x
20%
ai
=
0.000033
lb
ai).
The
amount
of
1,2­
benzisothiazolin­
3­
one
used
for
mopping
is
assumed
to
be
0.00025
lb
ai
(
i.
e.,
8.3
lb
cleaning
solution/
gal
x
0.15
lb/
1000
lb
cleaning
solution
x
20%
ai).

The
results
of
the
short­
term
risk
assessment
for
cleaning
products
are
presented
in
Table
10.
Using
the
assumptions
discussed
above,
the
calculated
short­
term
dermal
MOEs
are
9,000
and
48,000
for
the
wipe
and
mop
scenarios,
respectively.
The
short­
term
inhalation
MOEs
are
160,000
(
wipe)
and
590,000
(
mop).
The
total
risks
(
inhalation
+
dermal)
are
represented
by
the
total
MOE
of
8,500
and
44,000
for
wiping
and
mopping,
respectively.
Therefore,
for
the
cleaning
solutions
containing
1,2­
benzisothiazolin­
3­
one,
the
risks
do
not
exceed
the
Agency's
level
of
concern.
26
Table
10.
Estimates
of
Short­
term
Exposures
and
Risks
to
Residential
Handlers
of
1,2­
benzisothiazolin­
3­
one
Product
Scenario
Absorbed
Dermal
Dosea
(
mg/
kg/
day)
Inhalation
Dosea
(
mg/
kg/
day)
Dermal
MOEb
(
Target
MOE=
100)
Inhalation
MOEc
(
Target
MOE
=
100)
Total
MOEd
(
Target
MOE
=
100)

Paint
Paint
brush/
roller
0.013
4E­
05
370
130,000
370
Airless
sprayer
0.035
0.00089
140
5,600
140
Cleaning
Wiping
0.00055
3.2E­
05
9,000
160,000
8,500
Mopping
0.00010
8.5E­
06
48,000
590,000
44,000
a
Inhalation/
Absorbed
Dermal
Dose
(
mg/
kg/
day)
=
(
Application
Rate
(
lb
ai)
*
Inhalation/
Dermal
Unit
Exposure
(
mg/
lb
ai)
)/
Body
Weight
(
70
kg),
where
dermal
absorption
is
41
percent.
b
Dermal
MOE=
Dermal
NOAEL
(
5
mg/
kg/
day)/
Absorbed
Dermal
Dose
(
mg/
kg/
day).
c
Inhalation
MOE=
Inhalation
NOAEL
(
5
mg/
kg/
day)/
Inhalation
Dose
(
mg/
kg/
day).
d
Total
MOE
=
NOAEL
5
mg/
kg/
day
/
(
abs
dermal
dose
mg/
kg/
day
+
inhalation
dose).

5.5.2
Residential
Post­
application
Exposure
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
to
treated
surfaces
and
while
occupying
areas
where
pesticide
end­
use
products
have
recently
been
applied.
The
residential
post­
application
scenarios
considered
in
this
assessment
are
exposure
to
residues
from
hard
surfaces
(
i.
e.,
floors)
that
have
been
mopped
with
a
product
containing
1,2­
benzisothiazolin­
3­
one
and
the
use
of
laundry
detergents
containing
1,2­
benzisothiazolin­
3­
one
where
residues
could
remain
on
clothing
articles
after
laundering.
Although
residential
floors
are
believed
to
be
washed/
mopped
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
(
for
1,2­
benzisothiazolin­
3­
one,
the
dermal
and
incidental
oral
endpoints
and
uncertainty
factors
are
the
same
values
for
short­
and
intermediate­
term
durations).

Floor
Cleaner
Dermal
Exposure:

There
is
the
potential
for
dermal
exposure
to
toddlers
crawling
on
the
floor.
To
determine
toddler
exposure
to
residues
on
treated
floor,
the
following
equation
was
used:

PDD
FR
x
SA
BW
=

where
27
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%
1,2­
benzisothiazolin­
3­
one
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
1,2­
benzisothiazolin­
3­
one
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
absorbed
dermal
dose
and
the
dermal
MOE
are
presented
in
Table
11.
The
dermal
MOE
is
estimated
to
be
9,200
which
is
above
the
target
MOE
of
100,
and
therefore
not
of
concern.

Table
11.
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
Hard
Surfaces
(
floors)
0.657
m2
Median
surface
area
of
toddler
Body
Weight
15
kg
Median
body
weight
of
toddler
Table
11.
Short­
and
Intermediate­
term
Risks
Associated
with
Postapplication
Dermal
Exposure
on
Treated
Floors.

Parameter
Value
Rationale
28
Absorbed
Dermal
Dose
0.00055
mg/
kg/
day
TR
*
SA*
41%
dermal
Abs/
BW
Dermal
NOAEL
5
mg/
kg/
day
Dermal
MOE
9,200
(
Dermal
NOAEL)
/
(
Daily
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
1,2­
benzisothiazolin­
3­
one
via
incidental
oral
exposure.
To
calculate
incidental
ingestion
exposure
to
1,2­
benzisothiazolin­
3­
one
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
1,2­
benzisothiazolin­
3­
one
from
toddlers
crawling
on
treated
floors.
The
assumptions
above
in
the
dermal
assessment
(
Table
11)
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
to­
mouth
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
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
29
oral
exposure
is
not
of
concern
(
i.
e.,
above
the
target
MOE
of
300).

The
ARI
methodology
is
used
to
determine
the
total
risk
from
children
playing
on
BITtreated
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
[
ARI
=
1/((
target
dermal
MOE/
dermal
MOE)
+
(
target
oral
MOE/
oral
MOE))].
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
F1
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
=
water
mass
left
after
spin
cycle
(
kg)
/
total
water
mass
initially
present
(
kg),
FD
=
fabric
density
for
mixed
cotton
and
synthetics
(
10
mg/
cm2)
(
HERA
2003),
WI
=
total
weight
of
fabric
estimate
(
1E+
6
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),
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
Oral
Exposure
(
mg/
kg/
day)
=
[((
M
x
F1
x
FD)/
WI)
x
F1
x
Fm
x
SE]/
BW
where
M
=
amount
of
undiluted
product
used
(
e.
g.,
laundry
detergent),
150,000
mg
(
HERA
2003)
F1
=
water
mass
left
after
spin
cycle
(
kg)
/
total
water
mass
initially
present
(
kg),
FD
=
fabric
density
for
mixed
cotton
and
synthetics
(
10
mg/
cm2)
(
HERA
2003),
WI
=
total
weight
of
fabric
estimate
(
1E+
6
mg)
(
HERA
2003),
F1
=
weight
fraction
of
ai
applied
(
EPA
Reg
67071­
23,
0.15%
product
by
weight
x
20%
ai
=
30
0.03%
or
0.0003),
Fm
=
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
dermal
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.
However,
at
this
time,
F1
is
assumed
to
be
=
1,
when
in
reality
a
value
closer
to
0.01
is
more
probable.
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.

The
calculation
of
the
short­
and
intermediate­
term
oral
and
dermal
doses
and
MOEs
are
presented
in
Table
12.
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).

The
ARI
methodology
is
used
to
determine
the
total
risk
to
children
wearing
clothing
31
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].

Table
12.
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.

5.6
Residential
Exposures
and
Risks
from
Inert
Ingredient
Uses
1,2­
benzisothiazolin­
3­
one
is
an
inert
ingredient
in
over
900
different
products
and
is
used
primarily
as
a
materials
preservative.
The
types
of
products
that
contain
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient
include
turf
insecticides,
fungicides
and
herbicides;
garden
and
ornamental
insecticides;
flea
and
tick
control
products
for
pets;
indoor
crack
and
crevice
insecticides;
paints;
and
household
cleaners.
Since
1,2­
benzisothiazolin­
3­
one
is
also
used
as
an
active
ingredient
in
paints
and
household
cleaners
at
a
higher
percent
formulation
32
than
the
inert,
the
inert
exposure
assessment
did
not
include
an
analysis
of
the
paint
and
cleaning
products.
The
residential
exposure
assessment
(
section
4.3)
addresses
these
exposures
and
shows
that
the
MOEs
are
above
the
Agency's
level
of
concern.
Furthermore,
the
inert
assessment
did
not
specifically
evaluate
indoor
crack
and
crevice
uses
since
it
was
anticipated
the
applicator
exposures
resulting
from
the
outdoor
lawn
products
(
where
1,2­
benzisothiazolin­
3­
one
is
an
inert
ingredient)
would
result
in
higher
exposures
based
on
the
amount
used
per
day.
Additionally,
it
was
anticipated
the
post­
application
exposures
resulting
from
the
use
of
indoor
residential
cleaners
(
where
1,2­
benzisothiazolin­
3­
one
is
an
active
ingredient)
would
result
in
higher
exposures
when
considering
the
fact
that
exposure
to
residues
from
a
floor
cleaner
are
much
more
accessible
than
residues
applied
in
cracks/
crevices
and
along
baseboards.
An
inert
exposure
assessment
was
conducted
for
several
representative
residential
products
such
as
various
formulations
of
turf
and
garden
products
as
well
as,
flea
and
tick
pet
spray
products.

U.
S.
EPA's
Pesticide
Inert
Risk
Assessment
Tool
(
PiRat)
was
used
to
estimate
applicator
and
post­
application
exposure
and
risk
from
the
use
of
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient
in
representative
residential
products.
Background
information
and
the
downloadable
executable
file
for
PiRat
can
be
found
at
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
pirat.
htm.
All
of
PiRat's
default
values
were
used
in
each
run.
The
percent
formulation
of
0.1%
was
used
in
all
of
the
model
simulations.
This
value
was
based
on
the
tolerance
exemption
limitation
as
specified
in
40
CFR
180.920
and
a
review
of
several
Confidential
Statement
of
Formula
(
CSFs)
for
various
types
of
products.
As
previously
discussed,
since
1,2­
benzisothiazolin­
3­
one
is
used
in
numerous
types
of
products,
only
exposures
from
representative
high­
end
scenarios
were
estimated
using
PiRat.
These
scenarios
include
applicator
dermal
exposures
to
RTU,
EC,
and
granular
turf
products
and
toddler
dermal
and
incidental
ingestion
exposures
to
liquid
turf
products.
Again,
it
is
expected
that
the
indoor
crack
and
crevice
applicator
exposure
scenarios
would
result
in
lower
exposures
and
higher
MOEs.
The
applicator
exposures
and
risks
are
presented
in
Table
13
while
the
post­
application
exposures
and
risks
are
presented
in
Table
14.

Table
13.
Applicator
Short­
term
Exposures
and
MOEs
for
1,2­
benzisothiazolin­
3­
one
used
as
an
Inert
Ingredient
in
Outdoor
Products
Product
Use
Application
Method
Dermal
Exposure
mg/
kg/
day
Inhalation
Exposure
mg/
kg/
day
Dermal
MOE1
Inhalation
MOE1
Total
MOE2
Emulsifiable
Concentrate
Turf3
hose
end
sprayer;
MLAP
5.27
x
10­
4
4.07
x
10­
7
9,500
12,000,000
9,500
Granular
Turf3
push­
type
spreader;
LA
5.27
x
10­
5
2.70
x
10­
7
95,000
19,000,000
94,000
Ready
to
Use
Liquid
Turf
spot/
gardens
pump­
trigger;
APP
1.03
x
10­
2
2.74
x
10­
4
490
18,000
470
1
MOEs
=
NOAEL
/
exposure
where
dermal
and
inhalation
NOAELs
=
5.0
mg/
kg/
day.
Target
MOEs
$
100
33
2
Total
MOEs
were
estimated
since
dermal
and
inhalation
toxicological
effects
are
the
same.
Total
MOE
=
1
/
[(
1/
MOEdermal)
+
(
1/
MOEinhalation)]
3
an
application
rate
of
0.00015
lb
product/
ft2
was
assumed
for
all
scenarios
Table
14.
Toddler
Short­
term
Post­
Application
Exposures
and
MOEs
for
1,2­
benzisothiazolin­
3­
one
used
as
an
inert
in
outdoor
products
Product
Use
Route
of
Exposure
Exposure
mg/
kg/
day
MOE
Emulsifiable
Concentrate
Turf
Dermal
7.00
x
10­
3
710
Emulsifiable
Concentrate
Turf
Incidental
ingestion:
hand
to
mouth
9.81
x
10­
5
51,000
ARI
6.9
1
MOEs
=
NOAEL
/
exposure
where
dermal
and
inhalation
NOAELs
=
5.0
mg/
kg/
day.
Target
Dermal
MOE
$
100
and
Target
Oral
MOE
$
300
2
Aggregate
Risk
Index
(
ARI)
was
estimated
since
dermal
and
oral
toxicological
effects
are
the
same
but
the
target
MOEs
are
different.
Note:
ARI
$
1
are
not
of
concern.
ARI
=
1
/
[(
Target
MOEdermal/
MOEdermal)
+
(
Target
MOEoral/
MOEoral)]

1,2­
benzisothiazolin­
3­
one
is
also
used
in
several
pet
flea
and
tick
products.
Therefore,
applicator
dermal
and
inhalation
exposures
as
well
as
toddler
incidental
oral
and
dermal
postapplication
exposures
were
evaluated.
Although
PiRat
has
a
module
that
can
estimate
exposures
to
pet
products,
it
was
not
used
since
HED's
screening
level
methodologies
have
changed
since
the
development
of
PiRat.
Therefore,
the
most
recent
methodologies
were
utilized
to
assess
exposure
to
1,2­
benzisothiazolin­
3­
one
used
as
an
inert
ingredient
in
pet
products.

The
following
equation
and
assumptions
were
used
to
estimate
dermal
and
inhalation
residential
applicator
exposures
to
pet
product
residues:

Exposure
=
UE
x
AR
x
N
/
BW
where,
AR
=
Application
rate
(
lb
ai/
can)
UE
=
Unit
exposure
(
mg/
lb
ai)
N
=
Number
of
cans
(
cans/
day)
BW
=
Body
weight
(
kg)

All
of
the
input
parameters
are
defaults
provided
in
HEDs
Residential
SOPs
(
US
EPA,
1997
and
2001).
The
percent
formulation
of
0.1%
used
in
this
assessment
was
based
on
the
tolerance
exemption
limitation
as
specified
in
40
CFR
180.920
and
a
review
of
several
Confidential
Statements
of
Formula
(
CSFs)
for
the
various
types
of
products.
Table
15
provides
the
input
parameters
and
resulting
exposures
and
MOEs.
34
Table
15.
Applicator
Short­
term
Exposures
and
MOEs
for
1,2­
benzisothiazolin­
3­
one
used
as
an
Inert
Ingredient
in
Aerosol
Pet
Flea
and
Tick
Products
Exposure
=
UE
x
AR
x
N
/
BW
Dermal
Inhalation
Unit
Exposure
(
mg
/
lb
ai)
1
UE
220
2.4
Application
Rate
(
lb
ai/
can)
2
AR
0.0004
0.0004
Number
of
cans/
day
1
N
0.5
0.5
Percent
Absorption
41%
100%
Body
weight
(
kg)
1
BW
70
70
Daily
Dose
(
mg/
kg/
day)
2.52E­
04
6.70E­
06
Oral
NOAEL
(
mg/
kg/
day)
5
5
Target
MOE
100
100
MOE3
20,000
750,000
Total
MOE4
19,000
1
US
EPA,
1997
and
2001
(
HED's
Residential
SOPs)
2
6
oz/
can
x
0.1%
ai
x
1gal/
128oz
x
8.34lb/
gal
(
assuming
density
of
water)
3
MOEs
=
NOAEL
/
exposure
4
Total
MOEs
were
estimated
since
dermal
and
inhalation
toxicological
effects
are
the
same.
Total
MOE
=
1
/
[(
1/
MOEdermal)
+
(
1/
MOEinhalation)]

The
following
equation
and
assumptions
were
used
to
estimate
toddler
dermal
residential
post­
application
exposure
to
pet
product
residues:

Exposure
=
AR
x
T
x
SA
x
DA
/
BW
where,

AR
=
Application
rate
(
mg/
cm2
animal)
T
=
Transfer
fraction
from
treated
pet
(%)
SA
=
Surface
area
of
a
child
hug
(
cm2/
day)
DA
=
Dermal
absorption
(%)
BW
=
Body
weight
(
kg)

All
of
the
input
parameters
are
defaults
provided
in
HEDs
Residential
SOPs
(
US
EPA,
1997
and
2001).
The
percent
formulations
of
0.033%
and
0.1%
were
used
in
this
assessment.
Table
16
provides
the
input
parameters
and
resulting
exposures
and
MOEs.

Table
16.
Toddler
Short­
term
Post­
application
Dermal
Exposure
and
MOE
for
1,2­
benzisothiazolin­
3­
one
used
as
an
Inert
Ingredient
in
Aerosol
Pet
Flea
and
Tick
Products
35
Exposure
=
AR
x
T
x
SA
x
DA
/
BW
0.1%
formulation
0.033%
formulation
Application
Rate
(
mg/
cm2
of
animal)
1
AR
0.015
0.005
Transferable
Fraction2
T
20%
20%
Surface
area
of
a
child
hug
(
cm2)
2
SA
1,875
1,875
Dermal
Absorption
DA
41%
41%
Body
weight
(
kg)
2
BW
15
15
Daily
Dose
(
mg/
kg/
day)
0.15
0.05
Oral
NOAEL
(
mg/
kg/
day)
5
5
Target
MOE
100
100
MOE3
33
100
1
3
oz
x
%
formulation
/
6000cm2
x
1gal/
128oz
x
8.34lb/
gal
x
1kg/
2.2lb
x
1000g/
kg
x
1000mg/
g
where
it
was
assumed
that
½
of
6
oz
spray
container
is
applied
to
a
30
lb
animal
having
a
surface
area
of
6000cm2
2
US
EPA,
1997
and
2001
(
HED's
Residential
SOPs)
3
MOE
=
NOAEL
/
exposure
The
following
equation
and
assumptions
were
used
to
estimate
toddler
incidental
oral
residential
post­
application
exposure
to
pet
product
residues:

Exposure
=
AR
x
T
x
SA
x
SE
x
FQ
/
BW
where,
AR
=
Application
rate
(
mg/
cm2
animal)
T
=
Transfer
fraction
from
treated
pet
(%)
SA
=
Surface
area
of
a
child's
hands
(
cm2/
event)
SE
=
Saliva
extraction
(%)
FQ
=
Frequency
of
contact
(
event/
day)
BW
=
Body
weight
(
kg)

All
of
the
input
parameters
are
defaults
provided
in
HEDs
Residential
SOPs
(
US
EPA,
1997
and
2001).
The
percent
formulation
of
0.1%
was
used
in
this
assessment.
Table
17
provides
the
input
parameters
and
resulting
exposures
and
MOEs.

Table
17.
Toddler
Short­
term
Post­
application
Incidental
Oral
Exposure
and
MOE
for
1,2­
benzisothiazolin­
3­
one
used
as
an
Inert
Ingredient
in
Aerosol
Flea
and
Tick
Pet
Products
Exposure
=
AR
x
T
x
SA
x
SE
x
FQ
/
BW
36
Application
Rate
(
mg/
cm2
of
animal)
1
AR
0.015
Transferable
Fraction2
T
20%
Surface
area
of
a
child's
hand
(
cm2)
2
SA
20
Dermal
Absorption
SE
50%
Frequency
(
events/
day)
3
FQ
1
Body
weight
(
kg)
2
BW
15
Daily
Dose
(
mg/
kg/
day)
0.0020
Oral
NOAEL
(
mg/
kg/
day)
5
Target
MOE
300
MOE4
2,500
1
3
oz
x
0.1%
ai/
6000cm2
x
1gal/
128oz
x
8.34lb/
gal
x
1kg/
2.2lb
x
1000g/
kg
x
1000mg/
g
where
it
was
assumed
that
½
of
6
oz
spray
container
is
applied
to
a
30
lb
animal
having
a
surface
area
of
6000cm2
2
US
EPA,
1997
and
2001
(
HED's
Residential
SOPs)
3
frequency
was
modified
to
reflect
transferable
residue
assumptions
which
is
based
on
a
5
minute
heavy
rubbing/
petting
technique
that
would
lead
to
significantly
higher
hand
concentrations
than
would
result
from
a
single
contact
4
MOE
=
NOAEL
/
exposure
Because
the
dermal
and
oral
toxicological
effects
are
the
same
but
the
target
MOEs
differ,
an
aggregate
risk
index
(
ARI)
is
assessed
for
the
total
toddler
exposure
to
the
pet
product
residues.
The
resulting
total
risk
(
ARI)
for
toddlers
exposed
to
1,2­
benzisothiazolin­
3­
one
residues
in
pet
products
are
of
concern
at
the
0.1%
formulation
(
1/((
100/
33)
+
(
300/
2500))
=
ARI
=
32).
Reducing
the
formulation
to
0.033%,
the
ARI
is
0.89
(
note:
at
0.03%
the
ARI
is
0.97).
It
should
be
noted
that
these
exposures
are
based
on
very
conservative
models
and
default
input
parameters.
The
"
transferable
fraction"
parameter
is
a
value
that
could
be
further
refined
with
chemical
specific
data.
However
at
this
time,
the
percent
transfer
factor
from
pet
fur
to
skin
is
considered
a
data
gap
and
is
necessary
to
appropriately
refine
this
dermal
exposure.

The
results
from
the
exposure
and
risk
assessment
for
1,2­
benzisothiazolin­
3­
one
used
as
an
inert
ingredient
in
other
residential
products
(
i.
e.,
turf,
garden,
indoor
crack
and
crevice,
paint,
and
cleaning
products)
show
that
all
of
the
individual
MOEs,
total
MOEs
and
ARIs
are
above
the
Agency's
level
of
concern.

6.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
Consequently,
even
though
no
pesticide
tolerances
have
been
established
for
1,2­
benzisothiazolin­
3­
one
the
standards
of
FQPA
must
still
be
met,
including
"
that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
37
other
exposures
for
which
there
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).
Aggregate
risk
assessment
were
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
several
months
to
lifetime)
exposures.

In
performing
aggregate
exposure
and
risk
assessments,
the
Office
of
Pesticide
Programs
has
published
guidance
outlining
the
necessary
steps
to
perform
such
assessments
(
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments,
November
28,
2001;
available
at
http://
www.
epa.
gov/
pesticides/
trac/
science/
aggregate.
pdf
).
Steps
for
deciding
whether
to
perform
aggregate
exposure
and
risk
assessments
are
listed,
which
include:
identification
of
toxicological
endpoints
for
each
exposure
route
and
duration;
identification
of
potential
exposures
for
each
pathway
(
food,
water,
and/
or
residential);
reconciliation
of
durations
and
pathways
of
exposure
with
durations
and
pathways
of
health
effects;
determination
of
which
possible
residential
exposure
scenarios
are
likely
to
occur
together
within
a
given
time
frame;
determination
of
magnitude
and
duration
of
exposure
for
all
exposure
combinations;
determination
of
the
appropriate
technique
(
deterministic
or
probabilistic)
for
exposure
assessment;
and
determination
of
the
appropriate
risk
metric
to
estimate
aggregate
risk
6.1
Acute
and
Chronic
Aggregate
Risks
The
acute
and
chronic
aggregate
risk
assessments
generally
include
only
dietary
and
drinking
water
exposures.
Drinking
water
exposure
is
not
expected
from
any
of
the
indoor
or
outdoor
uses
of
1,2­
benzisothiazolin­
3­
one
used
as
either
an
inert
or
active
ingredient.
Cumulative
acute
and
chronic
dietary
risk
estimates
from
indirect
food
uses
(
i.
e.,
use
in
foodcontact
packaging)
were
calculated
and
presented
in
Section
5.2,
while
the
dietary
exposures
from
the
inert
uses
were
presented
in
Section
5.3.
Table
18
presents
a
summary
of
these
exposures,
as
well
as
the
aggregate
risks.
The
acute
and
chronic
aggregate
risk
estimates
associated
with
1,2­
benzisothiazolin­
3­
one
are
well
below
the
Agency's
level
of
concern.
It
should
be
noted
that
the
acute
and
chronic
dietary
exposures
from
the
inert
uses
were
selected
from
the
low
range
values
as
presented
in
Tables
8
and
9.
It
is
reasonable
to
use
the
low
range
values
in
the
aggregate
assessment
given
number
of
conservative
assumptions
that
were
the
basis
for
the
inert
dietary
assessment.

Table
18.
Acute
and
Chronic
Aggregate
Dietary
Exposures
and
Risks
Acute
Chronic
Dietary
Exposure
Dietary
Exposure
(
mg/
kg/
day)
(
mg/
kg/
day)
38
Active
Inert
Aggregate
Active
Inert
Aggregate
Adults
1.6E­
03
1.3E­
03
2.9E­
03
1.6E­
03
4.8E­
04
2.1E­
03
Children
3.7E­
03
3.8E­
03
7.5E­
03
3.7E­
03
1.7E­
03
5.4E­
03
Adults
%
a
or
cPAD
9.4%
7.6%
17.1%
9.4%
2.8%
12.2%
Children
%
a
or
cPAD
21.1%
22.4%
44.1%
21.8%
10.0%
31.8%

6.2
Short­
and
Intermediate­
Term
Aggregate
Exposures
and
Risks
Short­
and
intermediate­
term
aggregate
exposures
and
risks
were
assessed
for
adults
and
children
that
could
be
exposed
to
1,2­
benzisothiazolin­
3­
one
residues
from
the
use
of
products
in
non­
occupational
environments.
This
includes
products
that
contain
1,2­
benzisothiazolin­
3­
one
as
either
the
active
or
inert
ingredient.
The
following
lists
summarizes
all
of
the
potential
sources
of
1,2­
benzisothiazolin­
3­
one
exposures
for
adults
and
children:

Adult
1,2­
benzisothiazolin­
3­
one
exposures
sources:
°
Handling
of
paint
containing
BIT
as
an
active
or
inert
ingredient
via
brush
°
Handling
of
paint
containing
BIT
as
an
active
or
inert
ingredient
via
sprayer
°
Handling
of
cleaning
products
containing
BIT
as
an
active
or
inert
ingredient
during
wiping
activities
°
Handling
of
cleaning
products
containing
BIT
as
an
active
or
inert
ingredient
during
mopping
activities
°
Wearing
BIT­
treated
clothing
°
Eating
food
having
BIT
residues
from
indirect
food
contact
via
the
active
ingredient
paper
packaging
use
°
Eating
food
having
BIT
residues
from
the
inert
ingredient
pesticide
use
°
Handling
of
EC,
granular
or
RTU
turf
and
garden
products
containing
BIT
as
an
inert
ingredient
°
Handling
of
pet
flea
control
products
containing
BIT
as
an
inert
ingredient
Child
1,2­
benzisothiazolin­
3­
one
exposures
sources:
°
Post­
application
exposures
to
cleaning
product
residues
containing
BIT
as
an
active
or
inert
ingredient
used
on
hard
surfaces
(
i.
e.,
floors)
°
Wearing
BIT­
treated
clothing
°
Eating
food
having
BIT
residues
from
indirect
food
contact
via
the
active
ingredient
paper
packaging
use
°
Eating
food
having
BIT
residues
from
the
inert
ingredient
pesticide
use
°
Post­
application
exposures
to
turf
residues
containing
BIT
as
an
active
or
inert
ingredient
°
Post­
application
exposures
to
pet
flea
control
product
residues
containing
BIT
as
an
inert
ingredient
The
use
patterns
of
the
products
and
probability
of
co­
occurrence
must
be
considered
when
selecting
scenarios
for
incorporation
in
the
aggregate
assessment.
In
the
case
of
1,2­
benzisothiazolin­
3­
one,
homeowner
painting
activities
occur
only
once
or
twice
a
year,
while
the
use
of
turf/
garden
and
pet
products
occurs
on
an
intermittent
basis.
Therefore
the
probability
39
of
co­
occurrence
and
the
potential
for
exposure
to
residues
from
these
products
on
the
same
day
is
highly
unlikely.
However,
it
is
likely
that
someone
could
clean
the
kitchen
(
mopping
and
wiping
activities)
as
well
as,
wear
clothing
treated
with
1,2­
benzisothiazolin­
3­
one
during
the
same
day.
Table
19
summarizes
the
scenarios
included
in
the
short­
and
intermediate­
term
aggregate
assessments.

Table
19
Exposure
Scenarios
Included
in
the
Aggregate
Assessments
Short­
term
Aggregate
Intermediate­
Term
Aggregate
Adults
°
chronic
dietary
­
inert
°
chronic
dietary
­
active
°
handling
cleaning
products
­
wiping
°
handling
cleaning
products
­
mopping
°
treated
clothing
°
chronic
dietary
­
inert
°
chronic
dietary
­
active
°
treated
clothing
Children
°
chronic
dietary
­
inert
°
chronic
dietary
­
active
°
post­
app
to
cleaning
product
­
mopping
°
treated
clothing
°
chronic
dietary
­
inert
°
chronic
dietary
­
active
°
post­
app
to
cleaning
product
­
mopping
°
treated
clothing
The
chronic
dietary
exposures
were
used
in
both
the
short­
and
intermediate­
term
aggregate
assessment
because
chronic
dietary
exposures
occur
nearly
every
day
(
as
opposed
to
acute
dietary
exposures
occurring
on
a
one­
time
basis).
Therefore,
short­
or
intermediate­
term
non­
dietary
exposures
have
a
much
higher
probability
to
cooccur
with
the
chronic
dietary
intake
rather
than
the
acute
dietary
intake.

Cleaning
activities
in
a
residential
setting
occur
on
a
short­
term
basis.
However,
the
BITcontaining
cleaning
products
are
also
labeled
for
use
in
institutional
settings
such
as
day
care
facilities
where
cleaning
activities
can
occur
on
an
intermediate­
term
basis.
Therefore,
children
could
have
exposure
to
cleaning
product
residues
on
a
more
continuous
basis
in
a
day
care
facility
thus,
these
post­
application
scenarios
were
included
in
the
intermediate­
term
aggregate
assessment.

Since
the
toxicity
endpoints
for
all
of
the
routes
of
exposure
(
oral,
dermal
and
inhalation)
are
based
on
the
same
study
and
same
toxic
effect,
all
routes
are
aggregated
together.
However,
the
aggregate
risk
index
(
ARI)
method
outlined
in
OPP
guidance
for
aggregate
risk
assessment
(
September
1,
2000,
Standard
Operating
Procedure
(
SOP)
for
Incorporating
Screening
Level
Estimates
of
Drinking
Water
Exposure
into
Aggregate
Risk
Assessments)
was
utilized
in
the
assessment.
This
method
was
used
because
the
oral,
dermal
and
inhalation
endpoints
have
different
uncertainty
factors
that
need
to
be
applied.
For
1,2­
benzisothiazolin­
3­
one,
all
endpoints
for
exposure
were
derived
from
a
subchronic
oral
study
in
dogs
however,
the
uncertainty
factors
1It
should
be
noted
that
the
inhalation
target
MOE
of
1,000
is
used
to
determine
whether
an
additional
inhalation
study
is
warranted.
However,
the
inhalation
target
MOE
used
in
the
aggregate
assessment
is
100.

40
(
i.
e.,
target
MOEs)
for
oral,
dermal
and
inhalation
routes
are
300,
100
and
1001,
respectively.
A
risk
index
$
1
indicates
a
risk
of
no
concern.
Tables
20
and
21
present
the
short­
and
intermediate­
term
exposures
used
in
the
aggregate
assessment,
respectively,
while
Tables
22
and
23
present
the
resulting
ARIs
for
the
short­
and
intermediate
term
aggregate
assessments,
respectively.

Table
20.
Exposures
for
Short­
term
Aggregate
Assessment
Dietary
Clothing
Hard
Surface
Cleaning
Exposure
Routes
(
mg/
kg/
day)
(
mg/
kg/
day)
(
mg/
kg/
day)
Active
Inert
Total
Post­
App
Applicator
Post­
App
Wipe
Mop
Mop
Adults
Oral
Ingestion
1.6E­
03
4.8E­
04
2.1E­
03
NA
NA
NA
NA
Inhalation
NA
NA
NA
NA
3.2E­
05
8.5E­
06
NA
Dermal
NA
NA
NA
4.5E­
04
5.5E­
04
1.0E­
04
NA
Toddlers
Oral
Ingestion
3.7E­
03
1.7E­
03
5.4E­
03
3.0E­
03
NA
NA
1.6E­
04
Inhalation
NA
NA
NA
NA
NA
NA
NA
Dermal
NA
NA
NA
7.0E­
04
NA
NA
5.5E­
04
Table
21.
Exposures
for
Intermediate­
term
Aggregate
Assessment
Dietary
Clothing
Hard
Surface
Exposure
Routes
(
mg/
kg/
day)
(
mg/
kg/
day)
(
mg/
kg/
day)
Active
Inert
Total
Post­
App
Post­
App
Mop
Adults
Oral
Ingestion
1.6E­
03
4.8E­
04
2.1E­
03
NA
NA
Inhalation
NA
NA
NA
NA
NA
Dermal
NA
NA
NA
4.5E­
04
NA
Toddlers
Oral
Ingestion
3.7E­
03
1.7E­
03
5.4E­
03
3.0E­
03
1.6E­
04
Inhalation
NA
NA
NA
NA
NA
Dermal
NA
NA
NA
7.4E­
04
5.5E­
04
41
Table
22
Short­
term
Aggregate
Risks
Dietary
Clothing
Hard
Surface
Cleaning
Exposure
Routes
Active
Inert
Total
Post­
App
Applicator
Post­
App
Total
ARI
Wipe
Mop
Adults
Oral
Ingestion
MOEs
3,100
10,000
2,400
NA
NA
NA
NA
NA
Inhalation
MOEs
NA
NA
NA
NA
160,000
590,000
NA
120,000
Dermal
MOEs
NA
NA
NA
11,000
9,100
50,000
NA
7,700
Total
MOE
8,600
46,000
NA
7,200
6.8
Toddlers
Oral
Ingestion
MOEs
1,400
2,900
930
1,700
NA
NA
31,000
31,000
Inhalation
MOEs
NA
NA
NA
NA
NA
NA
NA
NA
Dermal
MOEs
NA
NA
NA
7,100
NA
NA
9,100
9,100
ARI
5.2
48.5
48.5
1.9
MOE
=
NOAEL/
exposure
ARI
=
1/((
target
MOEoral/
MOEoral)
+
(
target
MOEdermal/
MOEdermal)
+
(
target
MOEinhalation/
MOEinhalation)

All
NOAELs
=
5
mg/
kg/
day
Target
MOE
oral
=
300
Target
MOE
dermal
=
100
Target
MOE
inhalation
=
100
42
Table
23
Intermediate­
term
Aggregate
Risks
Dietary
Clothing
Hard
Surface
Cleaning
Exposure
Routes
Active
Inert
Total
Post­
App
Post­
App
ARI
Mop
Adults
Oral
Ingestion
MOEs
3,100
10,000
2,400
NA
NA
Inhalation
MOEs
NA
NA
NA
NA
NA
Dermal
MOEs
NA
NA
NA
11,000
NA
7.5
Toddlers
Oral
Ingestion
MOEs
1,400
2,900
930
1,700
31,000
Inhalation
MOEs
NA
NA
NA
NA
NA
Dermal
MOEs
NA
NA
NA
7,100
9,100
ARI
5.2
48.5
1.9
MOE
=
NOAEL/
exposure
ARI
=
1/((
target
MOEoral/
MOEoral)
+
(
target
MOEdermal/
MOEdermal)
+
(
target
MOEinhalation/
MOEinhalation)
All
NOAELs
=
5
mg/
kg/
day
Target
MOE
oral
=
300
Target
MOE
dermal
=
100
Target
MOE
inhalation
=
100
The
short­
term
ARIs
for
adults
and
children
were
6.8
and
1.9,
respectively,
while
the
intermediate­
term
ARIs
for
adults
and
children
were
7.5
and
1.9,
respectively.
These
ARIs
indicate
that
there
is
reasonable
certainty
of
no
harm
from
using
BIT­
containing
products.
Taking
into
consideration
all
available
information
on
the
current
and
proposed
use
of
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient
in
pesticide
products,
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
when
considering
dietary
exposure
and
all
other
non­
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
it
is
concluded
that
the
exemption
from
the
requirement
of
a
tolerance
established
for
residues
of
1,2­
benzisothiazolin­
3­
one
in/
on
raw
agricultural
commodities
can
be
considered
reassessed
as
safe
under
section
408(
q)
of
the
FFDCA,
and
that
the
proposed
exemption
for
use
on
animals
can
be
established
and
considered
safe
as
part
of
this
408
finding.

7.0
CUMULATIVE
RISK
Section
408
of
the
FFDCA
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
43
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
Although
1,2­
benzisothiazolin­
3­
one
is
classifies
as
a
member
of
the
isothiazoline
class
of
compounds,
the
Agency
does
not
have,
at
this
time,
available
data
to
determine
whether
1,2­
benzisothiazolin­
3­
one
has
a
common
mechanism
of
toxicity
with
other
substances.

Guidance
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity
has
recently
been
finalized.
This
guidance
is
available
from
the
OPP
website
(
http://
www.
epa.
gov/
pesticides).

8.0
OCCUPATIONAL
EXPOSURE
A
detailed
human
exposure
risk
assessment
for
1,2­
benzisothiazolin­
3­
one
is
provided
in
the
attached
Appendix.
The
summary
of
the
exposures
and
risks
to
occupational
workers
are
presented
below.

8.1
Occupational
Handler
Formulated
Product
Handlers:

EPA
has
assessed
the
exposure
to
handlers
mixing/
loading/
applying
products
containing
the
active
ingredient.
The
following
handler
exposure
scenarios
which
involve
handling
the
formulated
product
were
assessed
for
1,2­
benzisothiazolin­
3­
one
to
represent
the
high
end
of
industrial
uses
of
the
formulated
product.

°
Pouring
the
BIT­
containing
liquid
biocide
preservative
into
industrial
process
intermediate
materials
(
dispersions,
slurries,
emulsions,
solutions,
etc.)
°
Pouring
the
BIT­
containing
liquid
biocide
preservative
into
industrial
process
water
for
leather
and
photo
processing
systems
°
Pouring
the
BIT­
containing
liquid
biocide
preservative
into
metalworking
fluid
°
Pouring
the
BIT­
containing
liquid
biocide
preservative
during
oil
field
activities
There
are
no
chemical­
specific
exposure
data
to
assess
primary
handler
applications.
Therefore,
dermal
and
inhalation
exposures
were
assessed
using
CMA
surrogate
exposure
data.
Specifically,
the
liquid
pour
for
preservative
data
from
CMA
were
used
as
surrogate
data
for
the
scenarios
involving
the
pouring
of
liquid
preservatives
into
industrial
process
intermediate
materials,
leather
and
photo
processing
systems,
and
oil
fields;
the
liquid
pour
for
metal
working
fluid
data
from
CMA
were
used
as
surrogate
data
for
the
liquid
pouring
of
preservatives
into
metalworking
fluid;
the
liquid
pump
for
preservative
data
from
CMA
were
used
as
surrogate
data
for
the
liquid
pumping
of
preservatives
into
oil
fields.
In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
44
residential
handler
exposures.

The
results
of
the
MOE
analysis
are
presented
in
Table
24.
The
calculated
short­
and
intermediate­
term
inhalation
and
dermal
MOEs
are
greater
than
the
target
MOEs,
and
therefore,
are
not
of
concern
(
Note:
the
dermal
MOE
for
commercial
painting
with
an
airless
sprayer
is
90).
In
addition,
the
total
MOEs
(
inhalation
+
dermal)
have
been
presented.
The
total
MOEs
are
all
greater
than
100,
indicating
no
risks
of
concern,
except
for
the
commercial
painting
with
an
airless
sprayer
where
the
total
MOE
=
85.

Material
Preservative
Handlers:

EPA
has
assessed
the
exposure
to
handlers
mixing/
loading/
applying
products
containing
the
active
ingredient
as
a
material
preservative,
not
the
formulated
product
(
previously
defined
as
"
secondary"
handlers).
For
example,
those
individuals
exposed
to
the
active
ingredient
as
a
direct
result
of
its
incorporation
into
an
end
use
product
(
e.
g.,
individuals
using
caulk
or
paint
that
in
itself
is
not
a
registered
product).
The
scenarios
assessed
have
been
selected
to
represent
the
high
end
of
exposure
to
these
types
of
products
such
as
application
of
stains,
water­
based
adhesives,
caulks,
sealants,
grouts,
spackling,
ready­
mixed
cements,
and
ready­
mixed
wallboard
compounds.
Based
on
end­
use
product
application
methods,
it
is
assumed
that
exposures
while
applying
paints
will
be
equal
to
or
greater
than
exposures
while
applying
building
materials.
(
Note:
metal
working
fluids
for
machinists
are
assessed
separately
below.)
The
following
material
uses
were
assessed
to
represent
the
high
end
of
exposure
to
1,2­
benzisothiazolin­
3­
one:

°
Handling
BIT­
containing
paint
through
brush/
roller
and
airless
sprayer
application
methods.
°
Handling
BIT­
containing
cleaning
products
through
wiping
and
mopping
application
methods.

These
handler
exposure
scenarios
were
assessed
using
surrogate
unit
exposure
data
from
PHED
Version
1.1
for
the
painting
scenarios
and
using
surrogate
unit
exposure
from
CMA
for
the
cleaning
product
scenarios.
For
the
painting
scenarios,
it
was
assumed
that
commercial
painters
apply
5
gallons
(
50
lbs)
of
paint
through
brush/
roller
application
methods
and
50
gallons
(
500
lbs)
of
paint
through
airless
sprayer
application
methods.
For
the
cleaning
product
scenarios,
it
was
assumed
that
occupational
handlers
(
i.
e.,
janitors)
use
1
liter
for
wiping
and
2
gallons
for
mopping.

The
results
of
the
MOE
analysis
for
the
occupational
handlers
are
also
presented
in
Table
24.
The
calculated
short­
and
intermediate­
term
inhalation
and
dermal
MOEs
are
greater
than
the
target
MOE,
and
therefore,
are
not
of
concern.
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
inhalation
MOE
is
830.
Because
this
risk
is
believed
to
be
an
overestimate
based
on
the
extrapolation
error
to
large
volumes
handled,
the
inhalation
MOE
of
830
will
not
trigger
a
45
confirmatory
inhalation
toxicity
study.
Moreover,
in
the
painting
scenarios
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.
Therefore,
the
dermal
MOE
of
90
for
the
airless
sprayer
may
be
an
overestimate
of
risk.

Table
24.
Estimates
of
Short­
and
Intermediate­
term
Risks
to
Occupational
Handlers
of
1,2­
benzisothiazolin­
3­
one
Scenarios
Use
Site
Category
Inhalation
MOEb
(
Target
MOE
=
100)
Dermal
MOEc
(
Target
MOE
=
100)
Total
MOE
(
Target
=
100)

Occupational/
Industrial
Handler
(
Formulated
Products)

Mixing/
loading/
applying
BITcontaining
biocides
using
liquid
open
pour
methods
for
preservation
of
industrial
process
intermediate
materials.
(
Gloves)
Material
Preservatives
20,000
1,300
1,200
Mixing/
loading/
applying
BITcontaining
biocides
using
liquid
open
pour
methods
for
industrial
process
and
water
system
use.
(
Gloves)
Industrial
Processes
and
Water
Systems
25,000
1,600
1,500
Mixing/
loading/
applying
BITcontaining
biocides
using
liquid
open
pour
methods
for
preservation
of
metalworking
fluids
(
Gloves)
Material
Preservatives
51,000
5,700
5,100
Mixing/
loading/
applying
BITcontaining
biocides
using
liquid
open
pour
methods
for
preservative
products
(
Gloves)
Oil/
gas
Drilling
fluids
7E+
06
4.5E+
05
4.2E+
05
Mixing/
loading/
applying
BITcontaining
biocides
using
liquid
pump
methods
for
preservative
products
(
Gloves)
Oil
Secondary
Recovery
830
130
110
Occupational
Material
Preservative
Handlers
(
In­
can
Preservatives)

Handling
BIT­
containing
cleaning
solutions
through
wiping
application
methods
(
No
gloves)
Material
Preservatives
79,000
4,500
4,300
Handling
BIT­
containing
cleaning
solutions
through
mopping
application
methods
(
No
gloves)
Material
Preservatives
290,000
24,000
22,000
Handling
BIT­
containing
paint
through
paint
brush/
roller
application
methods
(
No
gloves)
Material
Preservatives
50,000
190
190
Handling
BIT­
containing
paint
through
airless
sprayer
application
methods
(
No
gloves)
Material
Preservatives
1,700
90
85
a
Dermal
MOE
is
based
on
the
short­
and
intermediate­
term
NOAEL
of
5
mg/
kg/
day.
Target
MOE=
100
b
Inhalation
MOE
is
based
on
the
ST
and
IT
inhalation
NOAEL
of
5
mg/
kg/
day.
Target
MOE=
1000.
46
c
Total
MOE
=
NOAEL
of
5
mg/
kg/
day
/
(
abs
dermal
dose
+
inhalation
dose).
Target
MOE
=
100.

Metal
Working
Fluids:

Potential
inhalation
and
dermal
exposures
may
exist
when
using
treated
metal
working
fluids.
A
screening­
level
long­
term
inhalation
exposure
estimate
for
treated
metal
working
fluids
has
been
developed
using
the
OSHA
PEL
for
oil
mist.
The
Agency
conducted
the
screening
level
assessment
for
metal
working
fluids
using
the
USEPA/
OPPTS
Chemical
Engineering
Branch
(
CEB)
model
(
U.
S.
EPA,
1991).
The
CEB
model
uses
measured
and/
or
assumed
airborne
oil
mist
concentrations
for
metal
working
operations.
Since
no
measured
concentrations
are
available
for
1,2­
benzisothiazolin­
3­
one,
the
high­
end
oil
mist
concentration
is
based
on
the
OSHA's
Permissible
Exposure
Limit
(
PEL)
of
5
mg/
m3
(
NIOSH,
1998).
EPA
Reg.
No.
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
1,2­
benzisothiazolin­
3­
one
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.
Additionally,
the
following
assumption
were
made
in
the
assessment:
the
inhalation
rate
for
adults
is
1.25
m3
/
hr;
the
exposure
duration
is
8
hours;
and
body
weight
is
70
kg.
Using
these
assumptions,
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.
Therefore,
the
calculated
MOE
indicates
that
the
inhalation
risks
do
not
exceed
the
Agency's
level
of
concern
for
machinist
exposures
to
metal
working
fluid
(
i.
e.,
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
1,2­
benzisothiazolin­
3­
one
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
long­
term
dermal
MOE
is
200
(
i.
e.,
oral
NOAEL
of
5
mg/
kg/
day
/
absorbed
dermal
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.

8.2
Occupational
Post­
application
Exposure
Postapplication
exposures
may
occur
in
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
1,2­
benzisothiazolin­
3­
one
are
likely
to
be
minimal
when
compared
to
handler
exposure
because
of
dilution
during
processing
or
when
compared
to
machinists
using
the
MWF.
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
47
expected
and
the
vapor
pressure
of
1,2­
benzisothiazolin­
3­
one
is
low.

9.0
ECOTOXICOLOGY
ASSESSMENT
Environmental
Modeling/
Exposure
Environmental
exposure
modeling
was
not
conducted
for
the
indoor
uses
of
BIT
considered
in
this
RED.
Modeling
was
not
conducted
for
the
outdoor
oil
recovery
uses
of
BIT,
as
no
validated
methodology
is
currently
available
to
estimate
environmental
exposure
from
these
uses.
The
potential
exposure
to
terrestrial
and
aquatic
species
from
the
oil
recovery
uses
of
BIT
cannot
be
estimated
at
this
time,
as
there
is
currently
no
validated
model
available
for
such
a
purpose.
1,2­
benzisothiazolin­
3­
one
is
also
used
as
an
inert
ingredient
in
agricultural
pesticide
formulations,
which
do
result
in
outdoor
exposure.
However,
considering
BIT's
ready
biodegradation,
and
the
small
amount
(
0.02
lbs.
per
acre)
that
may
be
applied
to
crops,
BIT
is
not
likely
to
be
present
in
surface
or
ground
water
sources
at
substantial
concentrations
as
a
result
of
their
use
as
inert
ingredients
in
pesticide
products
and
therefore
it
was
not
necessary
to
conduct
any
modeling
activities
for
the
inert
uses.

Ecological
Hazard
and
Risk
The
available
ecological
effects
data
for
1,2­
benzisothiazolin­
3­
one
are
somewhat
limited.
Based
on
acute
toxicity
information,
1,2­
benzisothiazolin­
3­
one
displays
low
to
moderate
toxicity
to
birds
and
mammals.
It
is
moderately
toxic
to
freshwater
fish
and
invertebrates,
slightly
toxic
to
marine/
estuarine
fish,
and
highly
toxic
to
marine/
estuarine
invertebrates.
A
submitted
rat
developmental
study
provided
a
NOAEL
of
40
mg/
kg/
day.
There
was
no
aquatic
organism
chronic
toxicity
information
available
for
1,2­
benzisothiazolin­
3­
one.
Phytotoxicity
data
were
particularly
scant,
with
one
algae
acute
study
found
in
published
scientific
literature,
which
indicates
that
1,2­
benzisothiazolin­
3­
one
is
highly
toxic
to
green
algae.
Acute
oral
toxicity
data
for
1,2­
benzisothiazolin­
3­
one
are
shown
in
Table
25,
acute
ecotoxicity
data
are
shown
in
Table
26,
and
other
ecotoxicity
data
(
subacute
dietary,
dermal,
and
developmental)
are
shown
in
Table
27.

Table
25.
Acute
Oral
Toxicity
of
1,2­
benzisothiazolin­
3­
one
Species
LD50/
LC50
(
mg/
kg)
NOAEL/
NOAEC
Toxicity
Category
Bird
Bobwhite
quail
(
Colinus
virginianus)
453
NA
Moderately
toxic
Mammal
Rat
650
­
males
784
­
females
­­­
 
48
Table
26.
Acute
Ecotoxicity
of
1,2­
benzisothiazolin­
3­
one
Species
LD50/
LC50
(
mg/
kg)
NOAEL/
NOAEC
Toxicity
Category
Freshwater
Fish
Rainbow
Trout
(
Oncorhynchus
mykiss)
1.3
0.74
Moderately
toxic
Rainbow
Trout
(
Oncorhynchus
mykiss)
1.6
­­­
Moderately
toxic
Freshwater
Invertebrate
Waterflea
(
Daphnia
magna)
1.5
0.7
Moderately
toxic
Waterflea
(
Daphnia
magna)
3.3
1.4
Moderately
toxic
Estuarine/
Marine
Fish
Sheepshead
minnow
(
Cyprinodon
variegatus)
12.2
3.3
Slightly
toxic
Estuarine/
Marine
Invertebrates
Mysid
shrimp
(
Mysidopsis
bahia)
0.99
0.25
Highly
toxic
Pacific
oyster
(
Crassostrea
gigas)
0.047
0.024
Very
highly
toxic
Aquatic
Algae
Green
algae,
species
not
indicated
0.15
(
72­
hour
EC50)
­­­
­­­

Table
27.
Other
Toxicity
Studies
of
1,2­
benzisothiazolin­
3­
one
Species
LD50/
LC50
(
mg/
kg)
NOAEL/
NOAEC
LOAEL/
LOAEL
Toxicity
Category
Subacute
Dietary
Toxicity
of
1,2­
benzisothiazolin­
3­
one
to
Birds
Bobwhite
quail
(
Colinus
virginianus)
>
5620
­­­
­­­
Practically
non­
toxic
Acute
Dermal
Toxicity
of
1,2­
benzisothiazolin­
3­
one
to
Rats
Rats
>
2000
­­­
­­­
­­­

Developmental
Toxicity
of
1,2­
benzisothiazolin­
3­
one
to
Rats
Rats
­­­
40
100
 
49
The
indoor
uses
of
BIT
considered
in
this
RED
make
it
unlikely
that
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms
would
occur.
Facilities
using
BIT
for
indoor
industrial
applications
are
required
to
have
NPDES
permits
before
discharging
effluents
into
receiving
waters.
The
potential
exposure
to
terrestrial
and
aquatic
species
from
the
oil
recovery
uses
of
BIT
cannot
be
estimated
at
this
time,
as
there
is
currently
no
validated
model
available
for
such
a
purpose.

1,2­
benzisothiazolin­
3­
one
is
used
as
an
inert
ingredient
in
pesticide
products
but
the
allowable
amount
that
can
be
applied
is
small
(
not
more
than
0.1%
formulation
and
0.02
lbs.
per
acre).
Data
indicate
that
1,2­
benzisothiazolin­
3­
one
breaks
down
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
1,2­
benzisothiazolin­
3­
one's
ready
biodegradation
in
soil
and
small
application
amount
greatly
reduce
the
exposure
potential
for
terrestrial
and
aquatic
organisms.
Run­
off
into
surface
water
from
pesticidal
uses
is
likely
to
be
low
and
it
is
not
likely
to
be
present
in
water
sources
at
substantial
concentrations.
Therefore,
risk
to
non­
target
organisms
is
not
anticipated
from
the
use
of
1,2­
benzisothiazolin­
3­
one.

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

The
indoor
uses
of
BIT
addressed
in
this
document
are
unlikely
to
result
in
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms,
and
thus
have
a
low
risk
potential
for
Listed
Species.
The
potential
exposure
to
terrestrial
and
aquatic
species
from
the
oil
recovery
uses
of
BIT
cannot
be
estimated
at
this
time,
as
there
is
currently
no
validated
model
available
for
such
a
purpose.
The
high
toxicity
of
BIT
to
green
algae
and
invertebrate
species
suggests
that
potential
adverse
acute
effects
could
occur
to
some
species
if
environmental
contamination
from
BIT­
treated
oil
recovery
fluids
occurs.

1,2­
benzisothiazolin­
3­
one
is
used
as
an
inert
ingredient
in
pesticide
products
but
the
allowable
amount
that
can
be
applied
is
small
(
not
more
than
0.1%
formulation
and
0.02
lbs.
per
acre).
Data
indicate
that
1,2­
benzisothiazolin­
3­
one
breaks
down
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
1,2­
benzisothiazolin­
3­
one's
ready
biodegradation
in
soil
and
small
application
amount
greatly
reduce
the
exposure
potential
for
terrestrial
and
aquatic
organisms.
Run­
off
into
surface
water
from
pesticidal
uses
is
likely
to
be
low
and
it
is
not
likely
50
to
be
present
in
water
sources
at
substantial
concentrations.
Therefore,
risk
to
Federal
listed
species
and
critical
habitats
is
not
likely
to
occur
from
the
inert
ingredient
uses
of
1,2­
benzisothiazolin­
3­
one.

10.0
DATA
NEEDS
An
acute
inhalation
study
is
required
for
the
technical
grade
active
ingredient
based
on
new
waiver
criteria
and
advances
in
inhalation
technology
which
nullified
the
previous
waiver.

The
chemical
structure
of
BIT
is
not
believed
to
be
so
closely
related
to
CMIT/
MIT
that
an
argument
can
be
made
to
bridge
carcinogenicity
data
for
CMIT/
MIT
to
BIT.
Therefore,
EPA
requires
that
the
registrant
submit
carcinogenicity
data
for
BIT
to
support
the
metal
working
fluid
use.
Conversely,
the
registrant
may
claim
that
a
carcinogenicity
study
would
not
be
required
for
the
metalworking
fluid
use
if
the
use
is
for
"
enclosed
metalworking
systems".
Under
this
scenario,
it
has
been
determined
that
certain
toxicology
data
requirements
including
carcinogenicity
testing
would
be
held
in
reserve
pending
review
of
worker
exposure
in
such
enclosed
systems
(
July
5,
2005
memorandum
from
Norm
Cook,
Chief,
Risk
Assessment
and
Science
Support
Branch,
Antimicrobials
Division
to
Marshall
Swindell,
PM
33,
Regulatory
Management
Branch
I,
Antimicrobials
Division).

To
support
the
oil
recovery
uses
of
BIT,
the
following
ecological
effects
data
are
needed:

°
850.1075
(
Old
72­
1)
Freshwater
fish
acute
toxicity
test
with
a
warmwater
species,
preferably
Bluegill
sunfish,
using
TGAI
°
850.1075
(
old
72­
3)
Marine/
estuarine
fish
acute
toxicity
test,
preferably
with
Sheepshead
minnow,
using
TGAI
11.0
INCIDENT
REPORT
ASSESSMENT
Based
on
the
information
gathered
from
incident
data
reports,
there
were
no
adverse
findings
of
significance
for
1,2­
benzisothizolin­
3­
one.
51
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