Document ID: EPA-HQ-OPP-2005-0200-0013
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-22T05:00Z

United
States
Office
of
Prevention,
Pesticides
739­
R­
05­
007
Environmental
Protection
and
Toxic
Substances
September
2005
Agency
(
7510C)

Reregistration
Eligibility
Decision
for
1,2­
Benzisothiazolin­
3­
one
(
BIT)
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
CERTIFIED
MAIL
Dear
Registrant:

This
is
to
inform
you
that
the
Environmental
Protection
Agency
(
hereafter
referred
to
as
EPA
or
the
Agency)
has
completed
its
review
of
the
available
data
and
public
comments
received
related
to
the
preliminary
risk
assessments
for
the
antimicrobial
1,2­
benzisothiazolin­
3­
one
(
hereafter
referred
to
as
BIT).
The
enclosed
Reregistration
Eligibility
Decision
(
RED)
document
was
approved
on
September
29,
2005.
Public
comments
and
additional
data
received
were
considered
in
this
decision.

Based
on
its
review,
EPA
is
now
publishing
its
Reregistration
Eligibility
Decision
(
RED)
and
risk
management
decision
for
BIT
and
its
associated
human
health
and
environmental
risks.
A
Notice
of
Availability
will
be
published
in
the
Federal
Register
announcing
the
publication
of
the
RED.

The
RED
and
supporting
risk
assessments
for
BIT
are
available
to
the
public
in
EPA's
Pesticide
Docket
OPP­
2005­
0200
at:
http://
www.
epa.
gov/
edocket.

The
BIT
RED
was
developed
through
EPA's
public
participation
process,
published
in
the
Federal
Register
on
July
20,
2005,
which
provides
opportunities
for
public
involvement
in
the
Agency's
pesticide
tolerance
reassessment
and
reregistration
programs.
Developed
with
input
from
EPA's
advisory
committees
and
others,
the
public
participation
process
encourages
robust
public
involvement
starting
early
and
continuing
throughout
the
pesticide
risk
assessment
and
risk
mitigation
decision
making
process.
The
public
participation
process
encompasses
full,
modified,
and
streamlined
versions
that
enable
the
Agency
to
tailor
the
level
of
review
to
the
level
of
refinement
of
the
risk
assessments,
as
well
as
to
the
amount
of
use,
risk,
public
concern,
and
complexity
associated
with
each
pesticide.
Using
the
public
participation
process,
EPA
is
attaining
its
strong
commitment
to
both
involve
the
public
and
meet
statutory
deadlines.

Please
note
that
the
BIT
risk
assessment
and
the
attached
RED
document
concern
only
this
particular
pesticide.
This
RED
presents
the
Agency's
conclusions
on
the
dietary,
drinking
water,
occupational
and
ecological
risks
posed
by
exposure
to
BIT
alone.
This
document
also
contains
both
generic
and
product­
specific
data
that
the
Agency
intends
to
require
in
Data
Call­
Ins
(
DCIs).
Note
that
DCIs,
with
all
pertinent
instructions,
will
be
sent
to
registrants
at
a
later
date.
Additionally,
for
product­
specific
DCIs,
the
first
set
of
required
responses
will
be
due
90
days
from
the
receipt
of
the
DCI
letter.
The
second
set
of
required
responses
will
be
due
eight
months
from
the
receipt
of
the
DCI
letter.

As
part
of
the
RED,
the
Agency
has
determined
that
BIT
will
be
eligible
for
reregistration
provided
that
all
the
conditions
identified
in
this
document
are
satisfied,
including
implementation
of
the
risk
mitigation
measures
outlined
in
Section
IV
of
the
document.
Sections
IV
and
V
of
this
RED
document
describe
labeling
amendments
for
end­
use
products
and
data
requirements
necessary
to
implement
these
mitigation
measures.
Instructions
for
registrants
on
submitting
the
revised
labeling
can
be
found
in
the
set
of
instructions
for
product­
specific
data
that
accompanies
this
document.

Should
a
registrant
fail
to
implement
any
of
the
risk
mitigation
measures
outlined
in
this
document,
the
Agency
will
continue
to
have
concerns
about
the
risks
posed
by
BIT.
Where
the
Agency
has
identified
any
unreasonable
adverse
effect
to
human
health
and
the
environment,
the
Agency
may
at
any
time
initiate
appropriate
regulatory
action
to
address
this
concern.
At
that
time,
any
affected
person(
s)
may
challenge
the
Agency's
action.

If
you
have
questions
on
this
document
or
the
label
changes
necessary
for
reregistration,
please
contact
the
Chemical
Review
Manager,
Rebecca
M.
Miller,
at
(
703)
305­
0012.

Sincerely,

Frank
T.
Sanders
Director,
Antimicrobials
Division
REREGISTRATION
ELIGIBILITY
DECISION
for
1,2­
Benzisothiazolin­
3­
one
(
BIT)
List
C
CASE
3026
Approved
By:

Frank
T.
Sanders
Director,
Antimicrobials
Division
Attachment
Table
of
Contents
BIT
Reregistration
Team                       
i
Glossary
of
Terms
and
Abbreviations                 ...
ii
Executive
Summary                        .....
iv
I.
Introduction                           ..
1
II.
Chemical
Overview                       .
3
A.
Regulatory
History                    ..
3
B.
Chemical
Identification
                  ...
4
C.
Use
Profile                        ...
5
III.
Summary
of
BIT
Risk
Assessments                 
6
A.
Human
Health
Risk
Assessment               ...
6
1.
Toxicity
of
BIT                    .
6
2.
FQPA
Safety
                     
9
3.
Population
Adjusted
Dose
(
PAD)            ...
10
a.
Acute
PAD                   
10
b.
Chronic
PAD                 
10
4.
Dietary
Exposure
Assumptions             ..
10
5.
Dietary
(
Food)
Risk
Assessment             .
11
a.
Acute
and
Chronic
Dietary
Risk          
11
b.
Dietary
Exposure
for
Inert
Ingredient
Uses     .
12
c.
Dietary
Risk
from
Drinking
Water         
15
6.
Residential
Risk
for
Active
Ingredient
Uses        .
15
a.
Toxicity                    .
16
b.
Residential
Handler
Scenarios .         ..
17
i.
Exposure
Scenarios,
Data
and
Assumptions  ..
17
ii.
Residential
Handler
Risk
Estimates     ..
18
c.
Residential
Post­
Application
Exposure       .
19
i.
Exposure
Scenarios,
Data
and
Assumptions  ..
19
ii.
Residential
Post­
Application
Risk
Estimates  
19
7.
Residential
Risk
for
Inert
Ingredient
Uses.        ...
20
8.
Aggregate
Risk                    .
22
a.
Acute
and
Chronic
Aggregate
Risks        ..
22
b.
Short­
and
Intermediate­
Term
Aggregates
Exposures
and
Risks               .  .  
23
9.
Occupational
Risk    .              ..
26
a.
Occupational
Toxicity              .
26
b.
Occupational
Handler
Exposure          
27
c.
Occupational
Handler
Risk
Summary       ...
28
d.
Occupational
Post­
Application
Exposure      .
29
B.
Environmental
Risk
Assessment               ...
30
1.
Environmental
Fate
and
Transport           ...
30
2.
Ecological
Risk                    .
30
3.
Listed
Species
Consideration              ..
32
IV.
Risk
Management,
Reregistration,
and
Tolerance
Reassessment
Decision 
34
A.
Determination
of
Reregistration
Eligibility           .
34
B.
Public
Comments
and
Responses               .
34
C.
Regulatory
Position                     
35
1.
Food
Quality
Protection
Act
Findings          ...
35
a.
"
Risk
Cup"
Determination            .
35
b.
Determination
of
Safety
to
U.
S.
Population     ..
35
c.
Determination
of
Safety
to
Infants
and
Children   .
35
d.
Cumulative
Risks
            ..   ..
36
e.
Endocrine
Disruptor
Effects..           .
36
2.
Tolerance
Summary                  
37
a.
Tolerances
Currently
or
Proposed
to
be
Listed    
37
b.
Codex
Harmonization              .
37
D.
Regulatory
Rationale                    ..
38
1.
Human
Health
Risk
Management            .
38
a.
Dietary
(
Food)
Risk
Mitigation          ..
38
b.
Drinking
Water
Risk
Mitigation          
38
c.
Residential
Risk
Mitigation            
38
d.
Occupational
Risk
Mitigation           
39
i.
Handler
Exposure             .
39
ii.
Post­
Application
Risk
Mitigation      ..
39
2.
Environmental
Risk
Management            .
39
3.
Listed
Species
Considerations              
39
a.
The
Endangered
Species
Program         .
39
b.
General
Risk
Mitigation             .
40
V.
What
Registrants
Need
to
Do                    
41
A.
Manufacturing
Use
Products                 .
43
1.
Additional
Generic
Data
Requirements          
43
2.
Labeling
for
Technical
and
Manufacturing
Use
Products  ..
43
B.
End­
Use
Products                     ...
44
1.
Additional
Product­
Specific
Data
Requirements      .
44
2.
Labeling
for
End­
Use
Products             ..
45
VI.
Appendices                           .
46
A.
Table
of
Use
Patterns
for
BIT                ...
47
B.
Table
of
Generic
Data
Requirements
and
Studies
Used
to
Make
the
Reregistration
Decision                   ..
62
C.
Technical
Support
Documents                ..
67
D.
Bibliography
Citations                   ...
68
E.
Generic
Data
Call­
In                    ..
143
F.
Product
Specific
Data
Call­
In                 
144
G.
Batching
of
End­
Use
Products                ..
145
H.
List
of
All
Registrants
Sent
the
Data
Call­
In          ...
150
I.
List
of
Available
Forms                   ...
151
i
BIT
Reregistration
Team
Health
Effects
Risk
Assessment
Melba
Morrow
Cassi
Walls
Tim
McMahon
Michelle
Centra
Timothy
Leighton
Environmental
Fate
and
Ecological
Assessment
Najm
Shamim
Kathryn
Montague
Use
Analysis
Rebecca
Miller
Risk
Management
Rebecca
Miller
Registration
Support
Karen
Angulo
GLOSSARY
OF
TERMS
AND
ABBREVIATIONS
a.
i.
Active
Ingredient
aPAD
Acute
Population
Adjusted
Dose
APHIS
Animal
and
Plant
Health
Inspection
Service
ARTF
Agricultural
Re­
entry
Task
Force
BCF
Bioconcentration
Factor
CDC
Centers
for
Disease
Control
CDPR
California
Department
of
Pesticide
Regulation
CFR
Code
of
Federal
Regulations
ChEI
Cholinesterase
Inhibition
CMBS
Carbamate
Market
Basket
Survey
cPAD
Chronic
Population
Adjusted
Dose
CSFII
USDA
Continuing
Surveys
for
Food
Intake
by
Individuals
CWS
Community
Water
System
DCI
Data
Call­
In
DEEM
Dietary
Exposure
Evaluation
Model
DL
Double
layer
clothing
{
i.
e.,
coveralls
over
SL}
DWLOC
Drinking
Water
Level
of
Comparison
EC
Emulsifiable
Concentrate
Formulation
EDSP
Endocrine
Disruptor
Screening
Program
EDSTAC
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
EEC
Estimated
Environmental
Concentration.
The
estimated
pesticide
concentration
in
an
environment,
such
as
a
terrestrial
ecosystem.
EP
End­
Use
Product
EPA
U.
S.
Environmental
Protection
Agency
EXAMS
Tier
II
Surface
Water
Computer
Model
FDA
Food
and
Drug
Administration
FFDCA
Federal
Food,
Drug,
and
Cosmetic
Act
FIFRA
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
FOB
Functional
Observation
Battery
FQPA
Food
Quality
Protection
Act
FR
Federal
Register
GL
With
gloves
GPS
Global
Positioning
System
HIARC
Hazard
Identification
Assessment
Review
Committee
IDFS
Incident
Data
System
IGR
Insect
Growth
Regulator
IPM
Integrated
Pest
Management
RED
Reregistration
Eligibility
Decision
LADD
Lifetime
Average
Daily
Dose
LC50
Median
Lethal
Concentration.
Statistically
derived
concentration
of
a
substance
expected
to
cause
death
in
50%
of
test
animals,
usually
expressed
as
the
weight
of
substance
per
weight
or
volume
of
water,
air
or
feed,
e.
g.,
mg/
l,
mg/
kg
or
ppm.
LCO
Lawn
Care
Operator
LD50
Median
Lethal
Dose.
Statistically
derived
single
dose
causing
death
in
50%
of
the
test
animals
when
administered
by
the
route
indicated
(
oral,
dermal,
inhalation),
expressed
as
a
weight
of
substance
per
unit
weight
of
animal,
e.
g.,
mg/
kg.
LOAEC
Lowest
Observed
Adverse
Effect
Concentration
LOAEL
Lowest
Observed
Adverse
Effect
Level
LOC
Level
of
Concern
LOEC
Lowest
Observed
Effect
Concentration
mg/
kg/
day
Milligram
Per
Kilogram
Per
Day
MOE
Margin
of
Exposure
MP
Manufacturing­
Use
Product
MRID
Master
Record
Identification
(
number).
EPA's
system
of
recording
and
tracking
studies
submitted.
MRL
Maximum
Residue
Level
iii
N/
A
Not
Applicable
NASS
National
Agricultural
Statistical
Service
NAWQA
USGS
National
Water
Quality
Assessment
NG
No
Gloves
NMFS
National
Marine
Fisheries
Service
NOAEC
No
Observed
Adverse
Effect
Concentration
NOAEL
No
Observed
Adverse
Effect
Level
NPIC
National
Pesticide
Information
Center
NR
No
respirator
OP
Organophosphorus
OPP
EPA
Office
of
Pesticide
Programs
ORETF
Outdoor
Residential
Exposure
Task
Force
PAD
Population
Adjusted
Dose
PCA
Percent
Crop
Area
PDCI
Product
Specific
Data
Call­
In
PDP
USDA
Pesticide
Data
Program
PF10
Protections
factor
10
respirator
PF5
Protection
factor
5
respirator
PHED
Pesticide
Handler's
Exposure
Data
PHI
Pre­
harvest
Interval
ppb
Parts
Per
Billion
PPE
Personal
Protective
Equipment
PRZM
Pesticide
Root
Zone
Model
RBC
Red
Blood
Cell
RED
Reregistration
Eligibility
Decision
REI
Restricted
Entry
Interval
RfD
Reference
Dose
RPA
Reasonable
and
Prudent
Alternatives
RPM
Reasonable
and
Prudent
Measures
RQ
Risk
Quotient
RTU
(
Ready­
to­
use)
RUP
Restricted
Use
Pesticide
SCI­
GROW
Tier
I
Ground
Water
Computer
Model
SF
Safety
Factor
SL
Single
layer
clothing
SLN
Special
Local
Need
(
Registrations
Under
Section
24C
of
FIFRA)
STORET
Storage
and
Retrieval
TEP
Typical
End­
Use
Product
TGAI
Technical
Grade
Active
Ingredient
TRAC
Tolerance
Reassessment
Advisory
Committee
TTRS
Transferable
Turf
Residues
UF
Uncertainty
Factor
USDA
United
States
Department
of
Agriculture
USFWS
United
States
Fish
and
Wildlife
Service
USGS
United
States
Geological
Survey
WPS
Worker
Protection
Standard
EXECUTIVE
SUMMARY
The
Environmental
Protection
Agency
(
hereafter
referred
to
as
EPA
or
the
Agency)
has
completed
its
review
of
public
comments
on
the
human
health
and
environmental
risk
assessments
for
1,2­
benzisothiazolin­
3­
one
(
hereafter
referred
to
as
BIT)
and
is
issuing
its
risk
management
decision.
The
Agency
has
decided
BIT
is
eligible
for
reregistration
provided
all
measures
outlined
in
this
document
are
implemented.
BIT
is
an
antimicrobial
that
is
used
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.
1,2­
Benzisothiazolin­
3­
one
is
also
used
as
an
inert
ingredient
in
a
variety
of
products
as
a
materials
preservative.
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
reregistration
eligibility
decision
(
RED).
End­
use
products
are
formulated
as
either
a
soluble,
ready­
to­
use,
or
flowable
concentrates
(
all
of
which
are
considered
to
be
liquids).

Overall
Risk
Summary
The
Agency's
human
health
risk
assessment
indicates
few
risks
of
concern.
Acute
and
chronic
dietary
exposure
is
below
the
agency's
level
of
concern
for
general
U.
S.
populations
and
all
population
subgroups.
Likewise,
it
was
concluded
that
risk
from
exposure
of
BIT
in
drinking
water
would
also
not
represent
a
risk
of
concern
because
it
is
not
likely
to
be
in
drinking
water
sources
at
substantial
concentrations.
This
is
based
on
the
fact
that
BIT
readily
biodegrades,
is
applied
to
crops
via
inert
use
in
small
amounts
and
is
only
likely
to
come
into
contact
with
soil/
surface
water
via
paint
uses
in
small
amounts.
The
acute
and
chronic
aggregate
dietary
risk
assessment
estimates
associated
with
the
use
of
BIT
as
an
inert
or
active
ingredient
are
below
the
Agency's
level
of
concern.

Short
and
intermediate
term
residential
post­
application
and
handler
exposures
(
dermal,
inhalation
or
incidental
oral)
from
hard
surface
residues
did
not
exceed
the
Agency's
level
of
concern.
For
residential
exposure
and
risk,
the
toddler
post­
application
dermal
exposure
scenario
from
residues
remaining
on
pets
from
the
inert
use,
the
margin
of
exposure
(
MOE)
is
below
the
targeted
MOE,
indicating
that
this
scenario
is
a
risk
of
concern.

For
aggregate
exposure,
the
risk
estimates
associated
with
BIT
are
below
the
Agency's
level
of
concern.
In
cases
where
an
aggregate
risk
index
(
ARI)
was
used
to
assess
risk
because
of
the
different
uncertainty
factors
for
oral,
dermal
and
inhalation
exposure
scenarios,
the
risk
indices
suggested
that
there
is
reasonable
certainty
of
no
harm
from
using
products
containing
BIT.
Based
on
the
information
provided,
inhalation
exposures
were
not
considered
to
be
of
concern
with
regard
to
inhalation
risk
from
occupational
handler
scenarios;
however
the
dermal
MOE
indicated
that
the
dermal
risk
for
occupational
handlers
was
below
the
target
MOE
for
one
v
scenario,
handlers
of
BIT­
containing
paint
using
an
airless
sprayer.
While
the
inhalation
risk
may
be
an
underestimation
based
on
extrapolation
from
an
oral
study,
the
dermal
risk
is
based
on
a
number
of
conservative
assumptions
and
are
not
of
concern.
Dermal
and
inhalation
exposures
to
bystanders
from
the
occupational
use
of
BIT
are
also
expected
to
be
minimal.

The
indoor
uses
of
BIT
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.

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.
The
ecological
risks
from
the
use
of
BIT
suggest
that
because
of
the
high
toxicity
of
BIT
to
green
algae
and
invertebrate
species,
adverse
effects
to
the
environment
could
result
from
contamination
from
BIT­
treated
oil
recovery
fluids.

Dietary
Risk
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)
for
non­
cancer
risk.
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.
A
dietary
cancer
risk
assessment
could
not
be
performed
as
there
are
no
carcinogenicity
data
for
1,2­
benzisothiazolin­
3­
one.

Drinking
Water
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
drinking
water
sources
at
substantial
concentrations.
Residential
Risk
To
address
residential
exposure
dermal,
inhalation
and
incidental
oral
risks
were
assessed
for
the
active
and
inert
ingredient
uses
of
BIT.
The
residential
handler
scenarios
evaluated
are
considered
to
be
representative
of
all
possible
exposure
scenarios.
None
of
the
residential
handler
exposure
scenarios
or
post­
application
exposure
scenarios
exceeded
the
Agency's
level
of
concern.

For
the
inert
uses
of
BIT,
none
of
the
residential
handler
exposure
scenarios
exceeded
the
Agency's
level
of
concern.
Although
most
of
the
post­
application
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
resulting
in
risks
of
concern.

Aggregate
Risk
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
used
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.

The
short­
and
intermediate­
term
aggregate
assessments
were
conducted
for
adults
and
children.
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.
Therefore,
short­
and
intermediate­
term
aggregate
calculated
risks
are
below
the
Agency's
level
of
concern.
Please
note
that
the
inert
use
in
pet
products
is
considered
to
result
in
intermittent
exposures
and,
as
such,
were
not
included
in
the
aggregate
assessment.

Occupational
Risk
To
address
occupational
exposure,
short­
term
inhalation,
and
intermediate­
term
combined
dermal
and
inhalation
risks
were
assessed.
The
inhalation
exposures
are
not
of
concern
for
the
any
of
the
handler
scenarios
assessed
(
i.
e.,
MOEs
$
1,000).
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).
vii
Postapplication
exposures
may
occur
in
industrial
settings
around
the
water
systems
via
inhalation,
and
dermal
exposures
may
occur
while
maintaining
industrial
equipment.
However,
occupational
post­
application
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
metal
working
fluid.
Inhalation
exposures
are
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
1,2­
benzisothiazolin­
3­
one
is
low.

Ecological
Risk
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.

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
(
halflife
<
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
For
certain
use
categories,
the
Agency
assumes
there
will
be
minimal
environmental
exposure,
and
only
a
minimal
toxicity
data
set
is
required
(
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
1/
23/
04,
Appendix
A,
Section
IIB,
pg.
81).
Chemicals
in
these
categories
therefore
do
not
undergo
a
full
screening­
level
risk
assessment,
and
are
considered
to
fall
under
a
A
no
effect
@

determination.
The
active
ingredient
uses
of
1,2­
benzisothiazolin­
3­
one
fall
into
this
category.

The
inert
uses
of
1,2­
benzisothiazolin­
3­
one
are
also
considered
to
fall
under
a
"
no
effect"
determination,
for
the
following
reasons:
1.
The
allowable
amount
that
can
be
applied
is
small
(
not
more
than
0.1%
formulation
and
0.02
lbs.
per
acre).
2.
Data
indicate
that
1,2­
benzisothiazolin­
3­
one
breaks
down
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
3.
1,2­
Benzisothiazolin­
3­
one
=

s
ready
biodegradation
in
soil
and
small
application
result
in
minimal
to
no
terrestrial
or
aquatic
organism
exposure.

Regulatory
Decision
The
Agency
has
completed
its
review
and
has
determined
that
the
data
are
sufficient
to
support
reregistration
of
all
supported
products
containing
BIT.
The
Agency
is
issuing
this
RED
for
BIT,
as
announced
in
a
Notice
of
Availability
published
in
the
Federal
Register.

Summary
of
Mitigation
Measures
The
Agency
has
determined
that
BIT
is
eligible
for
reregistration
provided
the
mitigation
measures
described
in
this
document
are
implemented.

Residential
Risk
The
Agency
has
concluded
that
to
have
an
acceptable
MOE
for
toddler
dermal
postapplication
dermal
scenarios,
the
maximum
percent
BIT
as
an
inert
in
flea
and
tick
pet
products
is
0.033%.
The
Agency
target
MOE
for
this
exposure
scenario
is
100,
while
the
Agency
calculated
toddler
dermal
post­
application
MOE
is
33;
a
value
that
indicates
a
risk
of
concern.
All
pet
products
containing
BIT
as
an
inert
ingredient
must
contain
a
maximum
of
0.033%
BIT
in
order
mitigate
the
current
risk
that
the
flea
and
tick
pet
products
pose.

Data
Requirements
Additional
confirmatory
data
is
required
to
complete
the
reregistration
of
BIT.
A
complete
list
of
data
gaps
is
presented
Section
V
and
Appendix
B
(
Table
of
Generic
Data
Requirements).
In
addition,
product­
specific
data
is
required
for
all
products
containing
BIT
as
described
in
Section
V
of
this
document.
1
I.
Introduction
The
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
was
amended
in
1988
to
accelerate
the
reregistration
of
products
with
active
ingredients
registered
prior
to
November
1,
1984
and
amended
again
by
the
Pesticide
Registration
Improvement
Act
of
2003
to
set
time
frames
for
the
issuance
of
Reregistration
Eligibility
Decisions.
The
amended
Act
calls
for
the
development
and
submission
of
data
to
support
the
reregistration
of
an
active
ingredient,
as
well
as
a
review
of
all
submitted
data
by
the
U.
S.
Environmental
Protection
Agency
(
EPA
or
the
Agency).
Reregistration
involves
a
thorough
review
of
the
scientific
database
underlying
a
pesticide's
registration.
The
purpose
of
the
Agency's
review
is
to
reassess
the
potential
hazards
arising
from
the
currently
registered
uses
of
the
pesticide;
to
determine
the
need
for
additional
data
on
health
and
environmental
effects;
and
to
determine
whether
or
not
the
pesticide
meets
the
"
no
unreasonable
adverse
effects"
criteria
of
FIFRA.

On
August
3,
1996,
the
Food
Quality
Protection
Act
of
1996
(
FQPA)
was
signed
into
law.
This
Act
amends
FIFRA
to
require
tolerance
reassessment.
The
Agency
has
decided
that,
for
those
chemicals
that
have
tolerances
and
are
undergoing
reregistration,
the
tolerance
reassessment
will
be
initiated
through
this
reregistration
process.
The
Act
also
requires
that
by
2006,
EPA
must
review
all
tolerances
in
effect
on
the
day
before
the
date
of
the
enactment
of
the
FQPA.
FQPA
also
amends
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA)
to
require
a
safety
finding
in
tolerance
reassessment
based
on
factors
including
consideration
of
cumulative
effects
of
chemicals
with
a
common
mechanism
of
toxicity.
This
document
presents
the
Agency's
revised
human
health
and
ecological
risk
assessments;
and
the
Reregistration
Eligibility
Decision
(
RED)
for
1,2­
benzisothiazolin­
3­
one
(
BIT).

BIT
is
an
antimicrobial
that
is
used
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.
Exposures
and
risks
from
the
use
of
products
containing
1,2­
benzisothiazolin­
3­
one
as
both
the
active
and
inert
ingredients
were
assessed.

The
Agency
has
concluded
that
the
FQPA
Safety
Factor
for
1,2­
benzisothiazolin­
3­
one
should
be
removed
(
equivalent
to
1X)
based
on
(
1)
the
lack
of
evidence
of
increased
susceptibility
in
the
2­
generation
reproduction
toxicity
study
and
the
available
developmental
toxicity
data;
and
(
2)
the
risk
assessment
does
not
underestimate
the
potential
risk
for
infants
and
children.
Risks
summarized
in
this
document
are
those
that
result
only
from
the
use
of
the
active
ingredient
1,2­
benzisothiazolin­
3­
one.
The
Food
Quality
Protection
Act
(
FQPA)
requires
that
the
Agency
consider
available
information
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
toxic
mechanism
could
lead
to
the
same
adverse
health
effect
that
would
occur
at
a
higher
level
of
exposure
to
any
of
the
substances
individually.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
for
1,2­
benzisothiazolin­
3­
one
and
any
other
substances.
1,2­
benzisothiazolin­
3­
one
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
action,
therefore,
EPA
has
not
assumed
that
1,2­
benzisothiazolin­
3­
one
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative.

This
document
presents
the
Agency's
decision
regarding
the
reregistration
eligibility
of
the
registered
uses
of
BIT.
In
an
effort
to
simplify
the
RED,
the
information
presented
herein
is
summarized
from
more
detailed
information
that
can
be
found
in
the
technical
supporting
documents
for
BIT
referenced
in
this
RED.
The
revised
risk
assessments
and
related
addenda
are
not
included
in
this
document,
but
are
available
in
the
Public
Docket
at
http://
www.
epa.
gov/
edocket.

This
document
consists
of
six
sections.
Section
I
is
the
introduction.
Section
II
provides
a
chemical
overview,
a
profile
of
the
use
and
usage
of
BIT,
and
its
regulatory
history.
Section
III,
Summary
of
BIT
Risk
Assessment,
gives
an
overview
of
the
human
health
and
environmental
assessments,
based
on
the
data
available
to
the
Agency.
Section
IV,
Risk
Management,
Reregistration,
and
Tolerance
Reassessment
Decision,
presents
the
reregistration
eligibility
and
risk
management
decisions.
Section
V,
What
Registrants
Need
to
Do,
summarizes
the
necessary
label
changes
based
on
the
risk
mitigation
measures
outlined
in
Section
IV.
Finally,
the
Appendices
list
all
use
patterns
eligible
for
reregistration,
bibliographic
information,
related
documents
and
how
to
access
them,
and
Data
Call­
In
(
DCI)
information.
3
II.
Chemical
Overview
A.
Regulatory
History
There
are
43
active
products
containing
1,2­
benzisothiazolin­
3­
one
as
an
active
ingredient,
3
of
which
are
technical
products,
registered
under
Section
3
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA).
There
are
hundreds
of
products
that
have
inert
uses
for
1,2­
benzisothiazolin­
3­
one.
The
first
product
containing
1,2­
benzisothiazolin­
3­
one
was
registered
on
April
4,
1973.

B.
Chemical
Identification
­
Technical
BIT
S
NH
O
Common
name:
BIT
Chemical
name:
1,2­
Benzisothiazolin­
3­
one
Chemical
Family:
Isothiazolines
Empirical
formula:
C7H5NOS
CAS
Registry
No.:
2634­
33­
5
Case
number:
3026
OPP
Chemical
Code:
098901
Molecular
weight:
151.9
Trade
name(
s):
IPX,
Proxan,
Proxel,
Nipacide
BIT,
Mergal
BIT
Basic
manufacturer:
PromChem,
Arch
Chemicals,
ISP,
Clariant
Corp.,
and
Troy
Corp.

Technical
BIT
is
in
the
form
of
a
solid
paste
and
is
off­
white
to
brown
in
color.
BIT
has
a
melting
point
of
159.5­
160oC.
Three
separate
water
solubilities
were
provided
by
different
registrants:
1118
ppm
at
20oC,
1380
ppm
at
24oC,
EPA
database
(
EPI
Suite)
lists
the
solubility
of
2.1
g/
L
at
25
o
C.
BIT
has
a
vapor
pressure
of
4.4
x
10­
7mm
Hg
at
20oC,
9.8
x
10­
7mm
Hg
at
25oC,
and
2.78
x
10­
6
mm
Hg
at
25oC
C.
Use
Profile
The
following
is
information
on
the
currently
registered
uses
of
BIT
products
and
an
overview
of
use
sites
and
application
methods.
A
detailed
table
of
the
uses
of
BIT
eligible
for
reregistration
is
contained
in
Appendix
A.

Type
of
Pesticide:
Fungicide/
Fungistat
Bacteriostat
Microbicide/
Microbistat
Disinfectant
(
Bacteriocide/
Germicide)

Summary
of
Use:

Food:
BIT
is
used
as
an
inert
ingredient
on
many
crops
including
Caneberries,
Blackberries,
Blueberries,
Cranberries,
Strawberries,
Citrus,
Almond,
Apples,
Pears,
Apricots,
Cherries,
Nectarines,
Peaches,
Plums,
Prunes,
Cantaloupes,
Casaba
Melons,
Crenshaw
Melons,
Honeydew
Melons,
Muskmelons,
Watermelons,
Tomatoes,
Broccoli,
Brussel
Sprouts,
Cabbage,
Cauliflower,
Collards,
Kale,
Endive,
Spinach,
Lettuce,
Carrots,
Onions,
Radishes,
Rutabagas,
Guar,
Ginseng,
Beets,
and
Mustard.

Non­
Food:
BIT
is
also
used
as
an
inert
ingredient
on
Conifer
Plantings,
Ornamental
Flowering
Plants,
Ornamental
Lawns,
Ornamental
Woody
Shrubs,
Roses,
English
Ivy,
Ornamental
Trees,
Weeping
Fig,
Elm,
Oak,
Palm,
Arizona
Cypress,
and
Irish
Moss.

Residential:
BIT
is
used
as
an
active
ingredient
for
Nonagricultural
Buildings,
Perimeter
Soil
Treatment,
Domestic
Dwellings
(
Outdoor),
and
Hard
Nonporous
Surfaces.

Industrial:
BIT
is
used
as
an
active
ingredient
for
Pulp
and
Paper
Mill
Systems,
Secondary
Oil
Recovery
Injection
Water,
and
Heat
Exchanger
Water.

Materials
Preservatives:
BIT
is
used
as
an
active
ingredient
for
Adhesives,
Preservative
Incorporation,
Adhesives
(
Gums,
Joint
Cements,
Latex,
Tape
Muds,
Protein
based,
Starch
based,
Synthetic),
Caulking
Compounds,
Grouts,
Starch,
Wallboard
Joint
Compounds,
Mastics,
Sealants,
Coatings
(
Aqueous,
Lacquer,
Rosin,
Wood,
Protein
and
Starch
based),
Films,
Coatings
(
Paper,
Paper
Products
and
Paperboard),
Hides
and
Leather
Products,
Leather
Processing
Liquors
(
Preservative
Incorporation),
Metalworking
Cutting
Fluids
(
Preservative
Incorporation),
Oil
Recovery
Drill
Muds
and
Packer
Fluids
(
Preservative
Incorporation),
Paints
(
Acrylic,
Emulsion
and
Latex),
Synthetic
Polymers,
Latex
and
Latex
Emulsions,
Resin
Emulsions,
Cleansers,
Photographic
Solution,
Polishes,
Soap,
Wax,
Inks,
Liquid
Detergents,
Dyes,
Powdered
Detergents,
Floor
Wax,
Fabric
Softeners,
Tarnish
Agents,
Air
Fresheners,
Carpet
Shampoos,
Canvas,
Cordage,
rope,
twine,
Fabrics,
Casein,
5
Clay
Slurries,
Starch
Solutions,
Printing
Pastes,
Stains
(
preservative
incorporation),
Water
Based
Paints,
and
Concrete
Mixtures.

Target
Pests:
Staphylococcus
aureus,
pseudomonas
aeruginosa,
rhizopus
stolonifer,
aspergillus
pencilloides,
aspergillus
niger,
alternaria
radicina,
tricophyton
mentagrophytes,
salmonella
typhosa,
klebsiella
pneumoniae,
bacillus
subtilis,
bacillus
megaterium,
eschericha
coli,
proteus
vulagris.

Formulation
Types:
Granular
powder,
flowable
concentrate,
soluble
concentrate,
ready
to
use
solution.

Method
and
Rates
of
Application:
All
products
containing
BIT
as
an
active
ingredient,
including
ready­
to­
use
solutions,
are
used
in
manufacturing
processes
only.
For
laundry
detergents,
household
cleaning
products,
and
car
care
products,
0.10%
to
0.30%
of
BIT
is
added
by
weight.
When
used
as
a
materials
preservative,
0.05%
to
1%
of
BIT
is
added
by
weight.
Please
refer
to
Appendix
A
for
more
detailed
application
rates.
III.
Summary
of
BIT
Risk
Assessments
The
purpose
of
this
summary
is
to
assist
the
reader
by
identifying
the
key
features
and
findings
of
these
risk
assessments,
and
to
help
the
reader
better
understand
the
conclusions
reached
in
the
assessments.
The
human
health
and
ecological
risk
assessment
documents
and
supporting
information
listed
in
Appendix
C
were
used
to
formulate
the
safety
finding
and
regulatory
decision
for
BIT.
While
the
risk
assessments
and
related
addenda
are
not
included
in
this
document,
they
are
available
from
the
OPP
Public
Docket
and
may
also
be
accessed
on
the
Agency's
website
at
http://
epa.
gov/
docket.
Hard
copies
of
these
documents
may
be
found
in
the
OPP
public
docket
under
docket
number
OPP­
2004­
0200.
The
OPP
public
docket
is
located
in
Room
119,
Crystal
Mall
II,
1801
Bell
Street,
Arlington,
VA,
and
is
open
Monday
through
Friday,
excluding
Federal
holidays,
from
8:
30
a.
m.
to
4:
00
p.
m.

A.
Human
Health
Risk
Assessment
1.
Toxicity
of
BIT
A
brief
overview
of
the
toxicity
studies
used
for
determining
endpoints
in
the
human
health
dietary
risk
assessments
are
outlined
in
Table
2.
Further
details
on
the
toxicity
of
BIT
can
be
found
in
the
documents
"
Human
Exposure
Assessment
for
a
Reregistration
Submission
for
1,2­
Benzisothiazolin­
3­
one
(
BIT),"
dated
July
11,
2005;
"
Dietary
Risk
Assessment
of
1,2­
Benzisothiazolin­
3­
one
(
BIT)
for
Reregistration
Eligibility
Decision
(
RED)
Document,"
dated
July
12,
2005;
and
"
1,2­
Benzisothizolin­
3­
one
(
BIT)­
Revised
Report
of
the
Antimicrobials
Division's
Toxicology
Endpoint
Selection
Committee
(
ADTC),"
dated
April
22,
2005.
These
documents
are
available
on
Agency's
website
in
the
EPA
Docket
at
http://
www/
epa.
gov/
edocket.

The
Agency
has
reviewed
all
toxicity
studies
submitted
for
BIT
and
has
determined
that
the
toxicological
database
is
sufficient
for
reregistration.
The
studies
have
been
submitted
to
support
guideline
requirements.
Major
features
of
the
toxicology
profile
are
presented
below.
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
skin
irritation
(
Toxicity
Category
IV),
but
repeated
dermal
application
indicated
a
more
significant
skin
irritation
response.

Table
1.
Acute
Toxicity
of
1,2­
Benzisothiazolin­
3­
one
Technical
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
7
Guideline
No.
Study
Type
MRID
#(
s)
Results
Toxicity
Category
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
The
doses
and
toxicological
endpoints
selected
for
the
dietary
exposure
scenarios
are
summarized
in
Table
2
below.

Table
2.
Toxicological
Endpoints
for
BIT
(
Dietary)

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
intraspecies
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
nonglandular
and
glandular
regions
of
the
stomach.

Chronic
Dietary
All
populations
NOAEL=
5
mg/
kg/
day
UF
=
100
(
10x
inter­
species
extrapolation,
10x
intraspecies
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
nonglandular
and
glandular
regions
of
the
stomach.

Cancer:
No
cancer
data
available
for
1,2­
benzisothiazolin­
3­
one
UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose,
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
N/
A
=
Not
Applicable
Developmental
toxicity
studies
were
conducted
in
rats
with
maternal
effects
including
decreased
body
weight
gain,
decreased
food
consumption,
and
clinical
toxicity
signs
(
audible
breathing,
haircoat
staining
of
the
anogenital
region,
dry
brown
material
around
the
nasal
area)
as
well
as
increased
mortality.
Developmental
effects
consisted
of
increases
in
skeletal
abnormalities
(
extra
sites
of
ossification
of
skull
bones,
unossified
sternebra)
but
not
external
or
visceral
abnormalities.

In
a
two­
generation
reproduction
study,
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.

General
Toxicity
Observations
Subchronic
oral
toxicity
studies
showed
systemic
effects
after
repeated
oral
administration
including
decreased
body
weight,
increased
incidence
of
forestomach
hyperplasia,
and
non­
glandular
stomach
lesions
in
rats.
In
dogs,
the
effects
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.

The
Agency
has
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
post­
dose
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.

Dietary:
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
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.

Incidental
Oral:
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:
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
a
subchronic
toxicity
study
in
dogs.
The
target
MOE
is
100
for
residential
and
occupational
exposure.
9
Inhalation:
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).

Dermal
Penetration:
A
dermal
penetration
study
was
conducted
in
rats
in
which
a
10mg/
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:
All
acceptable
mutagenicity
studies
showed
a
negative
mutagenic
response
for
this
chemical.

Carcinogenicity:
Carcinogenicity
data
are
not
available
for
1,2­
benzisothiazolin­
3­
one.
These
data
are
required
to
support
the
metalworking
fluid
use.

Endocrine
Disruption
Potential:
EPA
is
required
under
the
Federal
Food
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
Endocrine
Disrupting
Screening
Program
(
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.

2.
FQPA
Safety
Factor
The
FQPA
Safety
Factor
(
as
required
by
the
Food
Quality
Protection
Act
of
1996)
is
intended
to
provide
an
additional
10­
fold
safety
factor
(
10X),
to
protect
for
special
sensitivity
in
infants
and
children
to
specific
pesticide
residues
in
food,
drinking
water,
or
residential
exposures,
or
to
compensate
for
an
incomplete
database.
The
FQPA
Safety
Factor
has
been
removed
(
i.
e.,
reduced
to
1X)
for
1,2­
benzisothiazolin­
3­
one
based
on
(
1)
the
lack
of
evidence
of
increased
susceptibility
in
the
2­
generation
reproduction
toxicity
study
and
the
available
developmental
toxicity
data;
and
(
2)
the
risk
assessment
does
not
underestimate
the
potential
risk
for
infants
and
children.
The
FQPA
Safety
Factor
assumes
that
the
exposure
databases
(
food,
drinking
water,
and
residential)
are
complete,
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern,
and
does
not
underestimate
the
potential
risk
for
infants
and
children.
These
criteria
have
been
met
for
1,2­
benzisothiazolin­
3­
one.
Based
on
the
analysis
of
submitted
developmental
toxicity
studies,
the
Agency
determined
that
no
special
FQPA
Safety
Factor
was
needed
since
there
were
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity.
3.
Population
Adjusted
Dose
(
PAD)

Dietary
risk
is
characterized
in
terms
of
the
Population
Adjusted
Dose
(
PAD),
which
reflects
the
reference
dose
(
RfD),
either
acute
or
chronic,
that
has
been
adjusted
to
account
for
the
FQPA
Safety
Factor
(
SF).
This
calculation
is
performed
for
each
population
subgroup.
A
risk
estimate
that
is
less
than
100%
of
the
acute
or
chronic
PAD
is
not
of
concern.

a.
Acute
PAD
Acute
dietary
risk
for
BIT
is
assessed
by
comparing
acute
dietary
exposure
estimates
(
in
mg/
kg/
day)
to
the
acute
Population
Adjusted
Dose
(
aPAD).
Acute
dietary
risk
is
expressed
as
a
percent
of
the
aPAD.
The
aPAD
is
the
acute
reference
dose
(
0.017
mg/
kg/
day)
modified
by
the
FQPA
safety
factor.
The
acute
reference
dose
was
derived
from
a
subchronic
toxicity
study
in
dogs
in
which
both
the
NOAEL
(
5.0
mg/
kg/
day)
and
the
LOAEL
(
20.0
mg/
kg/
day)
were
determined
based
on
the
incidence
of
emesis
and
clinical
chemistry
alterations
in
both
sexes.
This
study
was
further
supported
by
a
subchronic
toxicity
study
in
rats
in
which
both
the
NOAEL
(
8.42
mg
ai/
kg/
day)
and
the
LOAEL
(
25.26
mg
ai/
kg/
day)
were
determined
based
on
the
incidence
of
macroscopic
and
microscopic
lesions
in
both
sexes.
The
BIT
aPAD
is
0.017
mg/
kg/
day
based
on
a
reference
dose
of
0.017
mg/
kg/
day,
and
incorporating
the
FQPA
safety
factor
of
1X
for
the
overall
U.
S.
population
or
any
population
subgroups.

b.
Chronic
PAD
Chronic
dietary
risk
for
BIT
is
assessed
by
comparing
chronic
dietary
exposure
estimates
(
in
mg/
kg/
day)
to
the
chronic
Population
Adjusted
Dose
(
cPAD).
Chronic
dietary
risk
is
expressed
as
a
percent
of
the
cPAD.
The
cPAD
is
the
chronic
reference
dose
(
0.017
mg/
kg/
day)
modified
by
the
FQPA
safety
factor.
The
cPAD
was
derived
from
a
subchronic
toxicity
study
in
dogs
in
which
both
the
NOAEL
(
5.0
mg/
kg/
day)
and
the
LOAEL
(
20.0
mg/
kg/
day)
were
determined
based
on
the
incidence
of
emesis
and
clinical
chemistry
alterations
in
both
sexes.
This
study
was
further
supported
by
a
subchronic
toxicity
study
in
rats
in
which
both
the
NOAEL
(
8.42
mg
ai/
kg/
day)
and
the
LOAEL
(
25.26
mg
ai/
kg/
day)
were
determined
based
on
the
incidence
of
macroscopic
and
microscopic
lesions
in
both
sexes.
The
BIT
cPAD
is
0.017
mg/
kg/
day
based
on
a
reference
dose
of
0.017
mg/
kg/
day,
which
includes
the
incorporation
of
the
FQPA
safety
factor
(
1X)
for
the
overall
U.
S.
population
or
any
population
subgroups.

4.
Dietary
Exposure
Assumptions
Dietary
exposure
to
BIT
residues
occurs
primarily
from
the
antimicrobial
paper
uses
which
include:
slimicide
use
in
paper/
pulp
manufacturing,
paper
coatings
preservative,
and
paper
adhesive
preservatives.
Acute
and
chronic
dietary
exposure
assessments
were
conducted
using
FDA's
Center
for
Food
Safety
&
Applied
Nutrition's
(
CFSAN)
screening­
level
approach
as
presented
in
"
Preparation
of
Food
Contact
Notifications
and
Food
Additive
Petitions
for
Food
Contact
Substances:
Chemistry
Recommendations"
dated
April
2002.
Using
the
maximum
application
rates
and
US
FDA's
default
assumptions,
"
worst­
case"
dietary
concentration
values
were
calculated
by
the
Agency.
11
FDA's
method
utilizes
a
number
of
general
assumptions
for
calculating
the
amount
of
BIT
in
food
from
contacting
treated
paper
surfaces.
These
assumptions
include
the
following:
1)
the
food
contact
can
result
from
a
one
time
use
or
a
repeat
use
of
the
paper;
2)
the
consumption
factor
(
CF
or
fraction
of
food
that
contacts
the
packaging
surface)
represents
a
ratio
of
the
actual
weight
of
food
that
comes
into
contact
with
the
paper
packaging
to
the
total
weight
of
the
food
packaged
with
the
paper;
3)
the
CF
varies
based
on
type
of
packaging;
and
4)
100%
of
the
antimicrobial
present
in
the
packaging
migrates
into
the
food
commodities.

5.
Dietary
(
Food)
Risk
Assessment
a.
Acute
and
Chronic
Dietary
Risk
Generally,
a
dietary
risk
estimate
that
is
less
than
100%
of
the
acute
or
chronic
PAD
does
not
exceed
the
Agency's
risk
concerns.
Since
the
PADs
for
acute
and
chronic
exposures
are
identical,
the
dietary
risk
estimates
are
the
same
for
both
durations
of
exposure
in
this
case.
A
summary
of
acute
and
chronic
risk
estimates
are
shown
in
Table
3.

Risk
estimates
are
below
the
Agency's
level
of
concern.
For
adults,
the
combined
acute
and
chronic
dietary
risk
estimate
is
9.4%
of
the
acute
PAD
and
chronic
PAD.
For
children,
the
most
highly
exposed
population
subgroup,
the
combined
acute
and
chronic
dietary
risk
estimate
is
21.8%
of
the
acute
PAD
and
chronic
PAD.
Therefore,
acute
and
chronic
dietary
risk
estimates
are
below
the
Agency's
level
of
concern
for
all
population
subgroups.

Table
3.
Summary
of
Dietary
Exposure
and
Risk
for
1,2­
Benzisothiazolin­
3­
one
Acute
and
Chronic
Dietary
Population
Subgroup
EDI
(:
g/
person/
day)
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
Acute
and
Chronic
Dietary
Population
Subgroup
EDI
(:
g/
person/
day)
Dietary
Exposurea
(
mg/
kg/
day)
%
aPAD
and
%
cPAD
b
Combined
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
b.
Dietary
Exposure
for
Inert
Ingredient
Uses
Included
in
this
RED
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.

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
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.
13
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
4
and
5,
below.

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
4.
Estimated
Acute
Dietary
(
Food)
Risk
Estimates
for
Inert
Uses
of
BIT
95th
Percentile
of
Exposure
Population
Subgroup
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
Table
5.
Chronic
Dietary
(
Food)
Risk
Estimates
for
Inert
Uses
of
BIT
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%
15
Population
Subgroup
BIT
Estimated
Exposure,
mg/
kg/
day
%
cPAD2/

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
c.
Dietary
Risk
from
Drinking
Water
Drinking
water
exposure
to
pesticides
can
occur
through
ground
and
surface
water
contamination.
In
assessing
drinking
water
risks,
EPA
considers
acute
(
one
day),
chronic
(
longterm
and,
if
applicable,
cancer
(
overall)
exposure,
and
uses
either
modeling
or
monitoring
data,
if
available,
to
estimate
those
risks.
To
determine
the
maximum
contribution
from
water
allowed
in
the
diet,
EPA
first
looks
at
how
much
of
the
overall
allowable
risk
is
contributed
by
food
and
then
calculates
a
"
drinking
water
level
of
comparison"
(
DWLOC)
to
determine
whether
modeled
or
monitored
exposure
estimates
exceed
the
allowable
risk
level.
Estimated
drinking
water
concentrations
(
EDWCs)
that
are
above
the
corresponding
DWLOC
exceed
the
Agency's
level
of
concern.

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
drinking
water
sources
at
substantial
concentrations.
Therefore
a
quantitative
drinking
water
assessment
was
not
conducted.

6.
Residential
Risk
for
Active
Ingredient
Uses
Residential
exposure
assessment
considers
all
potential
pesticide
exposure,
other
than
exposure
due
to
residues
in
food
and
drinking
water.
Exposure
may
occur
during
and
after
application
methods
including
painting
via
brush/
roller
and
airless
sprayer;
handling
BITcontaining
cleaning
products
through
low­
pressure
spray,
wiping,
and
mopping;
and
the
washing
of
clothing/
textiles
with
BIT­
containing
laundry
detergents.
Each
route
of
exposure
(
oral,
dermal,
inhalation)
is
assessed,
where
appropriate,
and
risk
is
expressed
as
a
Margin
of
Exposure
(
MOE),
which
is
the
ratio
of
estimated
exposure
to
an
appropriate
No
Observed
Effect
Level
(
NOAEL)
does.
Based
on
the
application
methods,
BIT
has
been
assessed
for
the
residential
mixing/
loading/
applicator
(
or
"
handler")
exposure
and
for
children's
post­
application
exposure
that
may
occur
from
clothing/
textile
and
via
floor­
cleaning
products.

a.
Toxicity
The
toxicological
endpoints
and
associated
uncertainty
factors
used
for
assessing
the
nondietary
risks
for
BIT
are
listed
in
Table
6.

A
MOE
greater
than
or
equal
to
100
is
considered
adequately
protective
for
the
residential
exposure
assessment
for
the
dermal,
incidental
oral
and
inhalation
routes
of
exposure.
The
MOE
of
100
includes
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variation.

Table
6.
Toxicity
Endpoints
Selected
for
Assessing
Occupational
and
Residential
Risk
for
BIT
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOE,
UF,
Special
FQPA
SF,
for
Risk
Assessment
Study
and
Toxicological
Effects
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.

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.
17
Exposure
Scenario
Dose
Used
in
Risk
Assessment
(
mg/
kg/
day)
Target
MOE,
UF,
Special
FQPA
SF,
for
Risk
Assessment
Study
and
Toxicological
Effects
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
to­
route
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,
LOC
=
level
of
concern,
MOE
=
margin
of
exposure
b.
Residential
Handler
Scenarios
i.
Exposure
Scenarios,
Data
and
Assumptions
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
BIT­
containing
paint
through
brush/
roller
and
airless
spray
application
methods
and
handling
BIT­
containing
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
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).
All
homeowner
painting
scenarios
are
believed
to
be
best
represented
by
the
short­
term
exposure
duration.

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.

ii.
Residential
Handler
Risk
Estimates
Based
on
toxicological
criteria
and
potential
for
exposure,
the
Agency
has
conducted
dermal
and
inhalation
exposure
assessments.
A
MOE
greater
than
or
equal
to
100
is
considered
adequately
protective
for
the
residential
exposure
assessment
for
the
dermal,
incidental
oral
and
inhalation
routes
of
exposure.
The
MOE
of
100
includes
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variation.

A
summary
of
the
residential
handler
exposures
and
risk
are
presented
on
Table
7.
The
combined
risks
from
dermal
and
inhalation
exposures
for
all
scenarios
are
below
the
Agency's
level
of
concern.

Table
7.
Estimates
of
Short­
term
Exposures
and
Risks
to
Residential
Handlers
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
brush/
roller
0.013
4E­
05
370
130,000
370
Paint
Airless
sprayer
0.035
0.00089
140
5,600
140
Wiping
0.00055
3.2E­
05
9,000
160,000
8,500
Cleaning
Mopping
0.00010
8.5E­
06
48,000
590,000
44,000
19
c.
Residential
Post­
Application
Exposure
i.
Exposure
Scenarios,
Data
and
Assumptions
Residential
postapplication
exposures
result
when
bystanders
(
adults
and
children)
come
in
contact
with
BIT
in
areas
where
pesticide
end­
use
products
have
recently
been
applied
(
e.
g.,
treated
hard
surfaces/
floors),
or
when
children
incidentally
ingest
the
pesticide
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
hand­
to­
mouth
or
object­
to­
mouth
contact).
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.

There
is
the
potential
for
dermal
exposure
to
toddlers
crawling
on
the
floor.
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
EPA's
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments
were
used.

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
the
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.

ii.
Residential
Post­
Application
Risk
Estimates
Based
on
toxicological
criteria
and
potential
for
exposure,
the
Agency
has
conducted
dermal
and
incidental
oral
exposure
assessments.
A
MOE
greater
than
or
equal
to
100
is
considered
adequately
protective
for
the
residential
exposure
assessment
for
the
dermal,
incidental
oral
and
inhalation
routes
of
exposure.
The
MOE
of
100
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation.

A
summary
of
the
residential
handler
exposures
and
risk
are
presented
on
Table
8.
The
risks
from
dermal
and
incidental
oral
exposures
for
all
scenarios
are
below
the
Agency's
level
of
concern.
Table
8.
Summary
of
Short­
and
Intermediate­
Term
Residential
Postapplication
Exposures
and
Risks
for
BIT
Scenario
Dose
(
mg/
kg/
day)
MOE
(
Target
MOE>
100
for
dermal;
>
300
for
oral)
Dermal
Exposure
Treated
Floors
Residential
Setting
(
Children)
0.00055
9,200
Adults
0.00045
11,000
Treated
clothing
Children
0.00070
7,200
Incidental
Oral
Exposure
Treated
Floors
Residential
Setting
(
Children)
0.00016
(
ST)
7.7E­
5
(
lT)
31,000
(
ST)
65,000
(
IT)

Treated
clothing
Children
0.003
1,700
7.
Residential
Risk
for
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
than
the
inert,
the
inert
exposure
assessment
did
not
include
an
analysis
of
the
paint
and
cleaning
products.
The
residential
exposure
assessment
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.

All
of
the
input
parameters
used
in
this
assessment
are
defaults
provided
in
the
Agency's
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.
21
Tables
9­
11
provide
the
input
parameters
and
resulting
exposures
and
MOEs
for
the
inert
uses.

Table
9.
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)
UE
220
2.4
Application
Rate
(
lb
ai/
can)
AR
0.0004
0.0004
Number
of
cans/
day
N
0.5
0.5
Percent
Absorption
41%
100%
Body
weight
(
kg)
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
MOE
20,000
750,000
Total
MOE
19,000
Table
10.
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
Exposure
=
AR
x
T
x
SA
x
DA
/
BW
Application
Rate
(
mg/
cm2
of
animal)
AR
0.015
Transferable
Fraction
T
20%

Surface
area
of
a
child
hug
(
cm2)
SA
1,875
Dermal
Absorption
DA
41%

Body
weight
(
kg)
BW
15
Daily
Dose
(
mg/
kg/
day)
0.15
Oral
NOAEL
(
mg/
kg/
day)
5
Target
MOE
100
MOE
33
Table
11.
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
Application
Rate
(
mg/
cm2
of
animal)
AR
0.015
Transferable
Fraction
T
20%
Surface
area
of
a
child's
hand
(
cm2)
SA
20
Saliva
Extraction
SE
50%
Frequency
(
events/
day)
FQ
1
Body
weight
(
kg)
BW
15
Daily
Dose
(
mg/
kg/
day)
0.0020
Oral
NOAEL
(
mg/
kg/
day)
5
Target
MOE
300
MOE
2,500
Because
the
dermal
and
oral
toxicological
effects
are
the
same
but
the
target
MOEs
differ,
it
typically
would
be
necessary
to
estimate
an
ARI
for
the
total
toddler
exposure
to
the
pet
product
residues.
However,
since
the
dermal
MOE
is
less
than
the
target
MOE
of
100,
it
was
not
necessary
to
estimate
an
ARI
because
it
would
result
in
a
value
less
than
1.
Therefore,
the
dermal
risk
and
resulting
total
risk
(
ARI)
for
toddlers
exposed
to
1,2­
benzisothiazolin­
3­
one
residues
in
pet
products
are
of
concern.
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.

8.
Aggregate
Risk
The
Food
Quality
Protection
Act
amendments
to
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA,
Section
408(
b)(
2)(
A)(
ii))
require
"
that
there
is
a
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
will
typically
include
exposures
from
food,
drinking
water,
residential
uses
of
a
pesticide,
and
other
non­
occupational
sources
of
exposure.

a.
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.
Table
12
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
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
14
and
15.
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.
23
Table
12.
Acute
and
Chronic
Aggregate
Dietary
Exposures
and
Risks
(
mg/
kg/
day)
(
mg/
kg/
day)
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%

b.
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
list
summarizes
all
of
the
potential
sources
of
1,2­
benzisothiazolin­
3­
one
exposures
for
adults
and
children:

Adult
1,2­
benzisothiazolin­
3­
one
exposure
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
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
13
summarizes
the
scenarios
included
in
the
short­
and
intermediate­
term
aggregate
assessments.

Table
13.
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
concur
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.
A
risk
index
$
1
indicates
a
risk
of
no
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.
Therefore
shortterm
and
intermediate­
term
aggregate
risks
are
below
the
Agency's
level
of
concern.
25
Tables
14
and
15
present
the
resulting
ARIs
for
the
short­
and
intermediate
term
aggregate
assessments,
respectively.

Table
14.
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
590,00
0
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
Table
15.
Intermediate­
term
Aggregate
Risks
Dietary
Clothing
Hard
Surface
Cleaning
Exposure
Routes
Active
Inert
Total
Post­
App
Post­
App
ARI
Mop
Adults
Oral
Ingestion
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
9.
Occupational
Risk
Workers
can
be
exposed
to
a
pesticide
through
mixing,
loading,
and/
or
applying
a
pesticide,
or
re­
entering
treated
sites.
Occupational
handlers
of
BIT
include
formulated
product
handlers,
material
preservative
handlers,
and
metal
working
fluids
handlers.
Occupational
risk
for
all
of
these
potentially
exposed
populations
is
measured
by
a
Margin
of
Exposure
(
MOE)
which
determines
how
close
the
occupational
exposure
comes
to
a
No
Observed
Adverse
Effect
Level
(
NOAEL)
from
toxicological
studies.
In
the
case
of
BIT,
MOEs
greater
than
100
are
not
of
concern
to
the
Agency.
This
MOE
includes
the
standard
safety
factors
of
10X
for
intraspecies
variability
(
i.
e.,
differences
among
humans)
and
10X
for
interspecies
variability
(
differences
between
humans
and
animals).

Occupational
risk
is
assessed
for
exposure
at
the
time
of
application
(
termed
"
handler"
exposure)
and
is
assessed
for
exposure
following
application,
or
post­
application
exposure.
Application
parameters
are
generally
defined
by
the
physical
nature
of
the
formulation
(
e.
g.,
formula
and
packaging),
by
the
equipment
required
to
deliver
the
chemical
to
the
use
site,
and
by
the
application
rate
required
to
achieve
an
efficacious
dose.

For
more
information
on
the
assumptions
and
calculations
of
potential
risk
of
BIT
to
workers,
see
the
Occupational
Exposure
Assessment
section
in
the
"
Human
Health
Risk
Assessment
(
Revised),"
dated
July
11,
2005.

a.
Occupational
Toxicity
Please
see
Table
4
as
it
provides
a
listing
of
the
toxicological
endpoints
used
in
the
occupational
risk
assessment
for
BIT.
27
b.
Occupational
Handler
Exposure
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
exposures.

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).
This
includes
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.

Metal
Working
Fluids
Handlers:

The
potential
inhalation
and
dermal
exposure
may
exist
when
using
treated
metal
working
fluid.
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
assumptions
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.

A
screening­
level
long­
term
dermal
exposure
estimate
was
derived
from
the
2­
Hand
Dermal
Immersion
in
Liquid
Model
in
ChemSTEER
(
EPA/
OPPT).
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.

c.
Occupational
Handler
Risk
Summary
The
results
of
the
MOE
analysis
are
presented
in
Table
16.
The
calculated
short­
and
intermediate­
term
dermal
MOEs
are
greater
than
the
target
MOEs,
and
therefore,
are
not
of
concern
with
the
exception
of
the
dermal
MOE
for
commercial
painting
with
an
airless
sprayer
which
is
90.
However,
it
is
believed
that
the
paint
matrix
has
the
potential
to
reduce
the
dermal
exposure.
Moreover,
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
chemicalspecific
data.
Therefore,
the
dermal
MOE
of
90
for
the
airless
sprayer
may
be
an
overestimate
of
risk.
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.
As
mentioned
above,
the
Agency
believes
that
actual
29
dermal
exposures
resulting
from
this
scenario
are
likely
to
result
in
risks
that
do
not
exceed
the
Agency's
level
of
concern.

Table
16.
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
BIT­
containing
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
BIT­
containing
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
BIT­
containing
biocides
using
liquid
open
pour
methods
for
preservation
of
metalworking
fluids
(
Gloves)
Material
Preservatives
51,000
5,700
5,100
Mixing/
loading/
applying
BIT­
containing
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
BIT­
containing
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
d.
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
post­
application
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
metal
working
fluid.
No
postapplication
exposure
data
have
been
submitted
to
the
agency
to
determine
the
extent
of
postapplication
exposures
in
the
industrial
settings.
Inhalation
exposures
are
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
1,2­
benzisothiazolin­
3­
one
is
low.

B.
Environmental
Risk
Assessment
A
summary
of
the
Agency's
environmental
risk
assessment
is
presented
below.
The
following
risk
characterization
is
intended
to
describe
the
magnitude
of
the
estimated
environmental
risks
for
BIT
use
sites
and
any
associated
uncertainties.

For
detailed
discussions
of
all
aspects
of
the
environmental
risk
assessment,
see
the
document
"
Environmental
Risk
Assessment
and
Characterization
­
1,2­
Benzisothiazolin­
3­
one
(
BIT)",
dated
July
7,
2005.

1.
Environmental
Fate
and
Transport
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
Kd
values
estimated
to
be
between
1.24
and
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
Kow
value
of
20
at
25
o
C,
1,2­
benzisothiazolin­
3­
one
is
unlikely
to
bioaccumulate
in
aquatic
organisms.

2.
Ecological
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
are
limited,
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
17,
acute
ecotoxicity
data
are
shown
in
Table
18,
and
other
ecotoxicity
data
(
subacute
dietary,
dermal,
and
developmental)
are
shown
in
Table
19.
31
Table
17.
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
­­­
­­­

Table
18.
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
19.
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
­­­

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
(
halflife
<
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.

3.
Listed
Species
Consideration
Section
7
of
the
Endangered
Species
Act,
16
U.
S.
C.
Section
1536(
a)(
2),
requires
all
federal
agencies
to
consult
with
the
National
Marine
Fisheries
Service
(
NMFS)
for
marine
and
anadromous
listed
species,
or
the
United
States
Fish
and
Wildlife
Services
(
FWS)
for
listed
wildlife
and
freshwater
organisms,
if
they
are
proposing
an
"
action"
that
may
affect
listed
species
or
their
designated
habitat.
Each
federal
agency
is
required
under
the
Act
to
insure
that
any
action
they
authorize,
fund,
or
carry
out
is
not
likely
to
jeopardize
the
continued
existence
of
a
listed
species
or
result
in
the
destruction
or
adverse
modification
of
designated
critical
habitat.
To
jeopardize
the
continued
existence
of
a
listed
species
means
"
to
engage
in
an
action
that
reasonably
would
be
expected,
directly
or
indirectly,
to
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
the
species."
50
C.
F.
R.
'
402.02.
33
To
facilitate
compliance
with
the
requirements
of
the
Endangered
Species
Act
subsection
(
a)(
2)
the
Environmental
Protection
Agency,
Office
of
Pesticide
Programs
has
established
procedures
to
evaluate
whether
a
proposed
registration
action
may
directly
or
indirectly
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
any
listed
species
(
U.
S.
EPA
2004).
After
the
Agency=
s
screening­
level
risk
assessment
is
performed,
if
any
of
the
Agency=
s
Listed
Species
LOC
Criteria
are
exceeded
for
either
direct
or
indirect
effects,
a
determination
is
made
to
identify
if
any
listed
or
candidate
species
may
co­
occur
in
the
area
of
the
proposed
pesticide
use.
If
determined
that
listed
or
candidate
species
may
be
present
in
the
proposed
use
areas,
further
biological
assessment
is
undertaken.
The
extent
to
which
listed
species
may
be
at
risk
then
determines
the
need
for
the
development
of
a
more
comprehensive
consultation
package
as
required
by
the
Endangered
Species
Act.

For
certain
use
categories,
the
Agency
assumes
there
will
be
minimal
environmental
exposure,
and
only
a
minimal
toxicity
data
set
is
required
(
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
1/
23/
04,
Appendix
A,
Section
IIB,
pg.
81).
Chemicals
in
these
categories
therefore
do
not
undergo
a
full
screening­
level
risk
assessment,
and
are
considered
to
fall
under
a
Ano
effect@
determination.
The
active
ingredient
uses
of
1,2­
benzisothiazolin­
3­
one
fall
into
this
category.

The
inert
uses
of
1,2­
benzisothiazolin­
3­
one
are
also
considered
to
fall
under
a
"
no
effect"
determination,
for
the
following
reasons:

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
(
halflife
<
24
hours
in
sandy
loam
soil).

1,2­
Benzisothiazolin­
3­
one=
s
ready
biodegradation
in
soil
and
small
application
result
in
minimal
to
no
terrestrial
or
aquatic
organism
exposure.
IV.
Risk
Management,
Reregistration,
and
Tolerance
Reassessment
Decision
A.
Determination
of
Reregistration
Eligibility
Section
4(
g)(
2)(
A)
of
FIFRA
calls
for
the
Agency
to
determine,
after
submission
of
relevant
data
concerning
an
active
ingredient,
whether
or
not
products
containing
the
active
ingredient
are
eligible
for
reregistration.
The
Agency
has
previously
identified
and
required
the
submission
of
the
generic
(
i.
e.,
active
ingredient­
specific)
data
required
to
support
reregistration
of
products
containing
BIT
as
an
active
ingredient.
The
Agency
has
completed
its
review
of
these
generic
data,
and
has
determined
that
the
data
are
sufficient
to
support
reregistration
of
all
supported
products
containing
BIT.

The
Agency
has
completed
its
assessment
of
the
dietary,
occupational,
drinking
water,
and
ecological
risks
associated
with
the
use
of
pesticide
products
containing
the
active
ingredient
BIT.
The
Agency
has
determined
that
BIT
containing
products
are
eligible
for
reregistration
provided
that:
(
i)
current
data
gaps
and
confirmatory
data
needs
are
addressed;
(
ii)
the
risk
mitigation
measures
outlined
in
this
document
are
adopted;
and
(
iii)
label
amendments
are
made
to
reflect
these
measures
where
necessary.
Appendix
A
summarizes
the
uses
of
BIT
that
are
eligible
for
reregistration.
Appendix
B
identifies
the
generic
data
requirements
that
the
Agency
reviewed
as
part
of
its
determination
of
reregistration
eligibility
of
BIT
and
lists
the
submitted
studies
that
the
Agency
found
acceptable.
Data
gaps
are
identified
as
generic
data
requirements
that
have
not
been
satisfied
with
acceptable
data.

Based
on
its
evaluation
of
BIT,
the
Agency
has
determined
that
BIT
products,
unless
formulated
and
used
as
specified
in
this
document,
would
present
risks
inconsistent
with
FIFRA.
Accordingly,
should
a
registrant
fail
to
implement
any
of
the
risk
mitigation
measures
identified
in
this
document,
the
Agency
may
take
regulatory
action
to
address
the
risk
concerns
from
the
use
of
BIT.
If
all
changes
outlined
in
this
document
are
incorporated
into
the
product
formulations,
then
all
current
risks
for
BIT
will
be
substantially
mitigated
for
the
purposes
of
this
determination.

B.
Public
Comments
and
Responses
Through
the
Agency's
public
participation
process,
EPA
worked
with
stakeholders
and
the
public
to
reach
the
regulatory
decisions
for
BIT.
During
the
public
comment
period
on
the
risk
assessments,
which
closed
on
September
19,
2005,
the
Agency
received
comments
from
Acti­
Chem
Specialties,
Inc.;
Arch
Chemicals,
Inc.,
Clariant
Corporation;
International
Specialty
Products,
Rohm
&
Haas
Company,
and
Troy
Corporation
in
response
to
EPA's
draft
risk
assessment
(
RA)
for
BIT.
The
comments
submitted
by
these
registrants
include
areas
of
toxicology,
exposure,
and
risks.
The
Agency's
responses
to
these
comments
are
incorporated
into
the
risk
assessment
and
revised
chapters,
which
are
available
in
the
public
docket
at
www.
epa.
gov/
edocket,
docket
#
OPP­
2005­
0200.
35
C.
Regulatory
Position
1.
Food
Quality
Protection
Act
Findings
a.
"
Risk
Cup"
Determination
As
part
of
the
FQPA
tolerance
reassessment
process,
EPA
assessed
the
risks
associated
with
BIT.
The
Agency
has
concluded
that
the
tolerance
exemption
for
the
use
of
BIT
as
an
inert
ingredient
meets
the
FQPA
safety
standards
and
that
the
risk
from
dietary
(
food
sources
only)
exposure
is
within
the
"
risk
cup."
An
aggregate
assessment
was
conducted
for
exposures
through
food
and
residential
exposure.
The
Agency
has
determined
that
the
human
health
risks
from
these
combined
exposures
are
within
acceptable
levels.
In
reaching
this
determination,
EPA
has
considered
the
available
information
on
the
special
sensitivity
of
infants
and
children,
as
well
as
aggregate
exposure
from
food
and
water.

b.
Determination
of
Safety
to
U.
S.
Population
As
part
of
the
FQPA
tolerance
reassessment
process,
EPA
assessed
the
risks
associated
with
BIT.
The
Agency
has
determined
that
the
established
tolerance
exemption
for
BIT
meets
the
safety
standards
under
the
FQPA
amendments
to
section
408(
b)(
2)(
D)
of
the
FFDCA,
and
that
there
is
a
reasonable
certainty
no
harm
will
result
to
the
general
population
or
any
subgroup
from
the
use
of
BIT.
In
reaching
this
conclusion,
the
Agency
has
considered
all
available
information
on
the
toxicity,
use
practices
and
exposure
scenarios,
and
the
environmental
behavior
of
BIT.

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
used
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.

The
short­
and
intermediate­
term
aggregate
assessments
were
conducted
for
adults
and
children.
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.
The
aggregate
risk
index
(
ARI)
method
was
utilized
in
the
assessment.
Short­
and
intermediateterm
aggregate
calculated
risks
are
below
the
Agency's
level
of
concern.

c.
Determination
of
Safety
to
Infants
and
Children
EPA
has
determined
that
the
established
tolerance
exemption
for
1,2­
benzisothiazolin­
3­
one,
with
amendments
and
changes
as
specified
in
this
document,
meet
the
safety
standards
under
the
FQPA
amendments
to
section
408(
b)(
2)(
C)
of
the
FFDCA,
that
there
is
a
reasonable
certainty
of
no
harm
for
infants
and
children.
The
safety
determination
for
infants
and
children
considers
factors
of
the
toxicity,
use
practices,
and
environmental
behavior
noted
above
for
the
general
population,
but
also
takes
into
account
the
possibility
of
increased
dietary
exposure
due
to
the
specific
consumption
patterns
of
infants
and
children,
as
well
as
the
possibility
of
increased
susceptibility
to
the
toxic
effects
of
BIT
residues
in
this
population
subgroup.

No
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children.
In
determining
whether
or
not
infants
and
children
are
particularly
susceptible
to
toxic
effects
from
BIT
residues,
the
Agency
considered
the
completeness
of
the
database
for
developmental
and
reproductive
effects,
the
nature
of
the
effects
observed,
and
other
information.
The
FQPA
Safety
Factor
has
been
removed
(
i.
e.,
reduced
to
1X)
for
BIT
based
on:
(
1)
the
lack
of
evidence
of
increased
susceptibility
in
the
2­
generation
reproduction
toxicity
study
and
the
available
developmental
toxicity
data;
and
(
2)
the
risk
assessment
does
not
underestimate
the
potential
risk
for
infants
and
children.

d.
Cumulative
Risks
Risks
summarized
in
this
document
are
those
that
result
only
from
the
use
of
1,2­
benzisothiazolin­
3­
one.
The
Food
Quality
Protection
Act
(
FQPA)
requires
that
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
toxic
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
substances
individually.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
for
1,2­
benzisothiazolin­
3­
one.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

e.
Endocrine
Disruptor
Effects
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
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
as
the
Administrator
may
designate."
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).
37
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.

2.
Tolerance
Summary
No
pesticide
tolerances
have
been
established
for
BIT.
BIT
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
and
is
considered
reassessed.
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
risk
assessments
in
this
document
took
into
consideration
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.

The
existing
exemption
from
the
requirement
of
a
tolerance,
as
well
as
the
proposed
exemption,
are
summarized
in
Table
20.

a.
Tolerances
Currently
or
Proposed
To
Be
Listed
Under
40
CFR
§
180.920
Table
20.
Tolerance
Reassessment
Summary
for
BIT
Tolerance
Exemption
Expression
CAS
Number
40
CFR
§
Current
Limits
Reassessed
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.
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
(
pending).

b.
Codex
Harmonization
Currently
there
are
no
Codex
MRLs
established
for
BIT.
D.
Regulatory
Rationale
The
Agency
has
determined
that
BIT
is
eligible
for
reregistration
provided
that
additional
required
data
confirm
this
decision
and
that
the
risk
mitigation
measures
outlined
in
this
document
are
adopted,
and
label
amendments
are
made
to
reflect
these
measures.

The
following
is
a
summary
of
the
rationale
for
managing
risks
associated
with
the
use
of
BIT.
Where
labeling
revisions
are
warranted,
specific
language
is
set
forth
in
the
summary
tables
of
Section
V
of
this
document.

1.
Human
Health
Risk
Management
a.
Dietary
(
Food)
Risk
Mitigation
The
acute
and
chronic
dietary
exposure
estimates
for
the
active
ingredient
uses
are
below
the
Agency's
level
of
concern.
While
the
acute
risk
estimates
for
the
inert
uses
exceed
100%
of
the
aPAD
for
children,
considering
the
unrefined
and
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.
Therefore,
no
risk
mitigation
measures
are
required
to
address
exposure
to
BIT
residues
in
food.

b.
Drinking
Water
Risk
Mitigation
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
drinking
water
sources
at
substantial
concentrations.
Therefore
a
quantitative
drinking
water
assessment
was
not
conducted
and
no
risk
mitigation
measures
are
required.

c.
Residential
Risk
Mitigation
Residential
risk
estimates
for
the
uses
of
BIT
as
an
active
ingredient
are
below
the
Agency's
level
of
concern.
Therefore,
no
risk
mitigation
measures
are
required
to
address
exposure
to
BIT
from
these
uses.
However,
residential
risk
estimates
regarding
the
use
of
1,2­
benzisothiazolin­
3­
one
as
an
inert
ingredient
in
pet
flea
and
tick
products
exceed
the
Agency's
level
of
concern
for
children.

In
evaluating
the
inert
uses
in
pet
products,
the
percent
formulation
of
0.1%
was
used
in
the
assessment
based
on
the
tolerance
exemption
limitation
as
specified
in
40
CFR
180.920
and
a
review
of
the
formulations
of
various
products.
The
Agency
has
determined
that
in
a
percent
formulation
of
0.033%
BIT
would
result
in
the
target
MOE
of
100
for
the
scenario
of
toddler
post­
application
dermal
exposure,
which
will
adequately
address
the
Agency's
risk
concerns.
All
pet
products
containing
BIT
as
an
inert
ingredient
must
contain
a
maximum
of
0.033%
BIT
in
order
to
be
eligible
for
reregistration.
39
d.
Occupational
Risk
Mitigation
i.
Handler
Exposure
The
calculated
short­
and
intermediate­
term
dermal
MOEs
are
greater
than
the
target
MOEs,
and
therefore,
are
not
of
concern
with
the
exception
of
the
dermal
MOE
for
commercial
painting
with
an
airless
sprayer
which
is
90.
However,
it
is
believed
that
the
paint
matrix
has
the
potential
to
reduce
the
dermal
exposure.
Moreover,
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.
Therefore,
the
dermal
MOE
of
90
for
the
airless
sprayer
may
be
an
overestimate
of
risk.
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.
As
mentioned
above,
the
Agency
believes
that
actual
dermal
exposures
resulting
from
this
scenario
are
likely
to
result
in
risks
that
do
not
exceed
the
Agency's
level
of
concern.

ii.
Post­
Application
Risk
Mitigation
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
metal
working
fluid.
Inhalation
exposures
are
expected
to
be
minimal
because
aerosol
generation
is
not
expected
and
the
vapor
pressure
of
1,2­
benzisothiazolin­
3­
one
is
low,
therefore
no
risk
mitigation
measures
are
required.

2.
Environmental
Risk
Management
The
indoor
uses
of
BIT
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.
Therefore,
no
risk
mitigation
measures
are
required
When
used
as
an
inert
ingredient
in
pesticide
products
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,
no
risk
mitigation
measures
are
required.

3.
Listed
Species
Considerations
a.
The
Endangered
Species
Program
Section
7
of
the
Endangered
Species
Act,
16
U.
S.
C.
Section
1536(
a)(
2),
requires
all
federal
agencies
to
consult
with
the
National
Marine
Fisheries
Service
(
NMFS)
for
marine
and
anadromous
listed
species,
or
the
United
States
Fish
and
Wildlife
Services
(
FWS)
for
listed
wildlife
and
freshwater
organisms,
if
they
are
proposing
an
"
action"
that
may
affect
listed
species
or
their
designated
habitat.
Each
federal
agency
is
required
under
the
Act
to
insure
that
any
action
they
authorize,
fund,
or
carry
out
is
not
likely
to
jeopardize
the
continued
existence
of
a
listed
species
or
result
in
the
destruction
or
adverse
modification
of
designated
critical
habitat.
To
jeopardize
the
continued
existence
of
a
listed
species
means
"
to
engage
in
an
action
that
reasonably
would
be
expected,
directly
or
indirectly,
to
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
the
species."
50
C.
F.
R.
'
402.02.

To
facilitate
compliance
with
the
requirements
of
the
Endangered
Species
Act
subsection
(
a)(
2)
the
Environmental
Protection
Agency,
Office
of
Pesticide
Programs
has
established
procedures
to
evaluate
whether
a
proposed
registration
action
may
directly
or
indirectly
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
any
listed
species
(
U.
S.
EPA
2004).
After
the
Agency=
s
screening­
level
risk
assessment
is
performed,
if
any
of
the
Agency=
s
Listed
Species
LOC
Criteria
are
exceeded
for
either
direct
or
indirect
effects,
a
determination
is
made
to
identify
if
any
listed
or
candidate
species
may
co­
occur
in
the
area
of
the
proposed
pesticide
use.
If
determined
that
listed
or
candidate
species
may
be
present
in
the
proposed
use
areas,
further
biological
assessment
is
undertaken.
The
extent
to
which
listed
species
may
be
at
risk
then
determines
the
need
for
the
development
of
a
more
comprehensive
consultation
package
as
required
by
the
Endangered
Species
Act.

For
certain
use
categories,
the
Agency
assumes
there
will
be
minimal
environmental
exposure,
and
only
a
minimal
toxicity
data
set
is
required
(
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
1/
23/
04,
Appendix
A,
Section
IIB,
pg.
81).
Chemicals
in
these
categories
therefore
do
not
undergo
a
full
screening­
level
risk
assessment,
and
are
considered
to
fall
under
a
Ano
effect@
determination.
The
active
ingredient
uses
of
1,2­
benzisothiazolin­
3­
one
fall
into
this
category.

The
inert
uses
of
1,2­
benzisothiazolin­
3­
one
are
also
considered
to
fall
under
a
"
no
effect"
determination,
for
the
following
reasons:

1.
The
allowable
amount
that
can
be
applied
is
small
(
not
more
than
0.1%
formulation
and
0.02
lbs.
per
acre).
2.
Data
indicate
that
1,2­
benzisothiazolin­
3­
one
breaks
down
quickly
in
aerobic
soils
(
half­
life
<
24
hours
in
sandy
loam
soil).
3.
1,2­
Benzisothiazolin­
3­
one=
s
ready
biodegradation
in
soil
and
small
application
result
in
minimal
to
no
terrestrial
or
aquatic
organism
exposure.

b.
General
Risk
Mitigation
BIT
end­
use
products
(
EPs)
may
also
contain
other
registered
pesticides.
Although
the
Agency
is
not
proposing
any
mitigation
measures
for
products
containing
BIT
specific
to
federally
listed
species,
the
Agency
needs
to
address
potential
risks
from
other
end­
use
products.
Therefore,
the
Agency
requires
that
users
adopt
all
listed
species
risk
mitigation
measures
for
all
active
ingredients
in
the
product.
If
a
product
contains
multiple
active
ingredients
with
41
conflicting
listed
species
risk
mitigation
measures,
the
more
stringent
measure(
s)
should
be
adopted.

V.
What
Registrants
Need
to
Do
The
Agency
has
determined
that
BIT
is
eligible
for
reregistration
provided
that:
(
i)
additional
data
that
the
Agency
intends
to
require
confirm
this
decision;
and
(
ii)
the
risk
mitigation
measures
outlined
in
this
document
are
adopted,
and
(
iii)
label
amendments
are
made
to
reflect
these
measures.
The
additional
data
requirements
that
the
Agency
intends
to
obtain
will
include,
among
other
things,
submission
of
the
following:

For
BIT
technical
grade
active
ingredient
products,
the
registrant
needs
to
submit
the
following
items:

Within
90
days
from
receipt
of
the
generic
data
call
in
(
DCI):

1.
completed
response
forms
to
the
generic
DCI
(
i.
e.,
DCI
response
form
and
requirements
status
and
registrant's
response
form);
and
2.
submit
any
time
extension
and/
or
waiver
requests
with
a
full
written
justification.

Within
the
time
limit
specified
in
the
generic
DCI:

1.
cite
any
existing
generic
data
which
address
data
requirements
or
submit
new
generic
data
responding
to
the
DCI.

Please
contact
Rebecca
M.
Miller
at
(
703)
305­
0012
with
questions
regarding
generic
reregistration.

By
US
mail:
By
express
or
courier
service:
Document
Processing
Desk
(
DCI/
AD)
Document
Processing
Desk
(
DCI/
AD)
Rebecca
M.
Miller
Rebecca
M.
Miller
US
EPA
(
7510C)
Office
of
Pesticide
Programs
(
7510C)
1200
Pennsylvania
Ave.,
NW
Room
266A,
Crystal
Mall
2
Washington,
DC
20460
1801
S.
Bell
Street
Arlington,
VA
22202
For
end
use
products
containing
the
active
ingredient
BIT,
the
registrant
needs
to
submit
the
following
items
for
each
product.

Within
90
days
from
the
receipt
of
the
product­
specific
data
call­
in
(
PDCI):

1.
completed
response
forms
to
the
PDCI
(
i.
e.,
PDCI
response
form
and
requirements
status
and
registrant's
response
form);
and
2.
submit
any
time
extension
or
waiver
requests
with
a
full
written
justification.

Within
eight
months
from
the
receipt
of
the
PDCI:

1.
two
copies
of
the
confidential
statement
of
formula
(
EPA
Form
8570­
4);

2.
a
completed
original
application
for
reregistration
(
EPA
Form
8570­
1).
Indicate
on
the
form
that
it
is
an
"
application
for
reregistration";

3.
five
copies
of
the
draft
label
incorporating
all
label
amendments
outlined
in
Table
23
of
this
document;

4.
a
completed
form
certifying
compliance
with
data
compensation
requirements
(
EPA
Form
8570­
34);
and
5.
if
applicable,
a
completed
form
certifying
compliance
with
cost
share
offer
requirements
(
EPA
Form
8570­
32);
and
6.
the
product­
specific
data
responding
to
the
PDCI.

Please
contact
Marshall
Swindell
at
(
703)
308­
8045
with
questions
regarding
product
reregistration
and/
or
the
PDCI.
All
materials
submitted
in
response
to
the
PDCI
should
be
addressed
as
follows:

By
US
mail:
By
express
or
courier
service:
Document
Processing
Desk
(
PDCI/
PRB)
Document
Processing
Desk
(
PDCI/
PRB)
Marshall
Swindell
Marshall
Swindell
US
EPA
(
7508C)
Office
of
Pesticide
Programs
(
7508C)
1200
Pennsylvania
Ave.,
NW
Room
266A,
Crystal
Mall
2
Washington,
DC
20460
1801
South
Bell
Street
Arlington,
VA
22202
43
A.
Manufacturing
Use
Products
1.
Additional
Generic
Data
Requirements
The
generic
database
supporting
the
reregistration
of
BIT
has
been
reviewed
and
determined
to
be
substantially
complete.
However,
the
following
additional
data
requirements
have
been
identified
by
the
Agency
as
confirmatory
data
requirements.
A
generic
data
call­
will
be
issued
at
a
later
date.

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.

The
Agency
has
established
an
interim
two­
tiered
system
for
toxicology
testing
requirements.
Tier
I
toxicology
data
requirements
would
apply
to
all
indirect
food
additives
that
result
in
residue
concentrations
ranging
from
0­
200ppb
which
applied
to
BIT.
The
requirements
would
consist
of
an
acute
toxicity
testing
battery,
subchronic
toxicity
study
in
the
rodent,
a
developmental
toxicity
study
in
the
rat,
and
a
mutagenicity
testing
battery.
Each
of
these
data
requirements
has
been
fulfilled
for
BIT.
The
Agency
also
conducts
a
literature
search
and
can
also
conduct
a
Structural
Activity
Review
(
SAR)
if
appropriate.
The
Agency
also
will
hold
in
reserve
a
two­
generation
reproduction
toxicity
study
in
the
rat
and
a
subchronic
toxicity
studies
in
a
non­
rodent
which
would
become
data
requirements
if
the
Agency's
evaluation
of
the
Tier
1
data
warranted.
A
2­
generation
reproduction
study
is
being
held
in
reserve
for
BIT.
A
subchronic
toxicity
study
in
a
non­
rodent
species
is
available
for
BIT.

Tier
II
studies
would
be
triggered
by
the
presence
of
significant
(
i.
e.
>
200ppb)
residues
in
food
or
evidence
of
significant
toxicity
from
the
Tier
I
data
set,
which
may
include
developmental
/
reproductive,
or
other
systemic
toxicity
such
as
presence
of
neoplastic
growth
or
significant
target
organ
toxicity.
In
such
cases,
chronic
toxicity
and
carcinogenicity
testing
would
be
required.

The
risk
assessment
noted
deficiencies
in
the
surrogate
dermal
and
inhalation
exposure
data
available
from
the
Chemical
Manufacturers
Association
(
CMA)
data
base.
Therefore,
the
Agency
is
requiring
confirmatory
data
to
support
the
uses
assessed
with
the
CMA
exposure
data
within
this
risk
assessment.
The
risk
assessment
also
noted
that
many
of
the
use
parameters
(
e.
g.,
amount
handled
and
duration
of
use)
were
based
on
professional
judgments.
Therefore,
descriptions
of
human
activities
associated
with
the
uses
assessed
are
required
as
confirmatory.

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
Table
21.
Confirmatory
Data
Requirements
for
Reregistration
Guideline
Study
Name
New
OPPTS
Guideline
No.
Old
Guideline
No.

Acute
Inhalation
Toxicity,
using
TGAI
870.1300
81­
3
Estuarine/
Marine
Fish
Acute
Toxicity,
preferably
with
Sheepshead
minnow,
using
TGAI
850.1075
72­
3
Freshwater
Fish
Acute
Toxicity
with
a
warmwater
species,
preferably
Bluegill
sunfish,
using
TGAI
850.1075
72­
1
Indoor
Inhalation
Exposure
and
Applicator
Exposure
Monitoring
Data
Reporting
875.1400
and
875.1600
234
and
236
Indoor
Dermal
Exposure
and
Applicator
Exposure
Monitoring
Data
Reporting
875.1200
and
875.1600
233
and
236
Descriptions
of
Human
Activity
875.2800
133­
1
Carcinogenicity
870.4200
83­
2
Studies
Held
in
Reserve
2­
Generation
Reproduction
870.3800
83­
4
2.
Labeling
for
Technical
and
Manufacturing
Use
Products
To
ensure
compliance
with
FIFRA,
technical
and
manufacturing
use
product
(
MP)
labeling
should
be
revised
to
comply
with
all
current
EPA
regulations,
PR
Notices
and
applicable
policies.

B.
End­
Use
Products
1.
Additional
Product­
Specific
Data
Requirements
Section
4(
g)(
2)(
B)
of
FIFRA
calls
for
the
Agency
to
obtain
any
needed
product­
specific
data
regarding
the
pesticide
after
a
determination
of
eligibility
has
been
made.
The
Registrant
must
review
previous
data
submissions
to
ensure
that
they
meet
current
EPA
acceptance
criteria
and
if
not,
commit
to
conduct
new
studies.
If
a
registrant
believes
that
previously
submitted
data
meet
current
testing
standards,
then
the
study
MRID
numbers
should
be
cited
according
to
the
instructions
in
the
Requirement
Status
and
Registrants
Response
Form
provided
for
each
product.

A
product­
specific
data
call­
in
will
be
issued
at
a
later
date.
45
2.
Labeling
for
End­
Use
Products
No
specific
labeling
changes
are
necessary
to
implement
measures
outlined
in
Section
IV
above.
However,
to
ensure
compliance
with
FIFRA
end
use
product
(
MP)
labeling
should
be
revised
to
comply
with
all
current
EPA
regulations,
PR
Notices
and
applicable
policies.