United
States
Office
of
Prevention,
Pesticides
EPA
739­
R­
05­
010
Environmental
Protection
and
Toxic
Substances
September
2005
Agency
(
7510C)

Reregistration
Eligibility
Decision
for
Azadioxabicyclooctane
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
preservative
referred
to
as
azadioxabicyclooctane.
The
enclosed
Reregistration
Eligibility
Decision
(
RED)
document
was
approved
on
September
30,
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
azadioxabicyclooctane
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
azadioxabicyclooctane
are
available
to
the
public
in
EPA's
Pesticide
Docket
OPP­
2005­
0186
at:
http://
www.
epa.
gov/
edockets.

The
azadioxabicyclooctane
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
reassessment
and
reregistration
programs.
Developed
in
partnership
with
USDA
and
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
azadioxabicyclooctane
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
azadioxabicyclooctane
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
azadioxabicyclooctane
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
azadioxabicyclooctane.
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,
Tom
Luminello,
at
(
703)
308­
8075.
For
questions
about
product
reregistration
and/
or
the
Product
Specific
DCI
that
accompanies
this
document,
please
contact
Marshall
Swindell
at
(
703)
308­
6341.

Sincerely,

Frank
T.
Sanders
Director,
Antimicrobials
Division
REREGISTRATION
ELIGIBILITY
DECISION
for
AZADIOXABICYCLOOCTANE
List
C
CASE
3023
Approved
By:

Frank
T.
Sanders
Director,
Antimicrobials
Division
Date
Attachment
Table
of
Contents
Azadioxabicyclooctane
Reregistration
Team                     
i
Glossary
of
Terms
and
Abbreviations                 
ii
Executive
Summary                        ....
v
I.
Introduction                           ..
1
II.
Chemical
Overview                       .
3
A.
Regulatory
History                    ..
3
B.
Chemical
Identification
                 
3
1.
Technical
Azadioxabicyclooctane            
4
C.
Use
Profile                        ..
4
D.
Estimated
Usage
of
Pesticide                 
III.
Summary
of
Azadioxabicyclooctane
Risk
Assessments         
5
A.
Human
Health
Risk
Assessment              
5
1.
Toxicity
of
Azadioxabicyclooctane                   
5
2.
FQPA
Safety
                     
8
3.
Population
Adjusted
Dose
(
PAD)            ...
8
a.
Acute
PAD                   
8
b.
Chronic
PAD                
9
4.
Exposure
Assumptions                 
9
5.
Dietary
(
Food)
Risk
Assessment             .
10
a.
Acute
Dietary
Risk               .
10
b.
Chronic
(
Non­
Cancer)
Dietary
Risk        ..
10
c.
Dietary
Risks
from
Drinking
Water        ..
10
6.
Residential
                     ..
11
a.
Toxicity       .            .
11
b.
Residential
Handler      ..       ..
12
c.
Residential
Application             ..
14
7.
Aggregate
Risk                    
14
a.
Short­
Term
Aggregate
Risk           .
14
8.
Occupational
Risk                  ...
14
a.
Occupational
Toxicity              .
15
b.
Occupational
Handler
Exposure          
15
c.
Occupational
Handler
Risk
Summary       ...
15
d.
Occupational
Post­
Application
Risk
Summary    
17
B.
Environmental
Risk
Assessment               ..
17
1.
Environmental
Fate
and
Transport           ...
17
2.
Ecological
Risk                   ..
18
3.
Listed
Species
Consideration              ..
21
IV.
Risk
Management,
Reregistration,
and
Tolerance
Reassessment
Decision 
23
A.
Determination
of
Reregistration
Eligibility           
23
B.
Public
Comments
and
Responses               .
23
C.
Regulatory
Position                     
24
1.
Food
Quality
Protection
Act
Findings          ...
24
a.
"
Risk
Cup"
Determination            .
24
b.
Determination
of
Safety
to
U.
S.
Population     .
24
c.
Determination
of
Safety
to
Infants
and
Children   
24
d.
Endocrine
Disruptor
Effects           ..
25
e.
Cumulative
Risks                .
25
D.
Regulatory
Rationale                    ..
26
1.
Human
Health
Risk
Management            .
26
a.
Dietary
(
Food)
Risk
Mitigation          .
26
b.
Drinking
Water
Risk
Mitigation         ..
26
c.
Residential
Risk
Mitigation            
26
d.
Occupational
Risk
Mitigation           
26
i.
Handler
Exposure             .
27
ii.
Post­
Application
Risk
Mitigation      .
27
2.
Environmental
Risk
Management          ..
27
3.
Other
Labeling
Requirements              
27
4.
Threatened
and
Endangered
Species
Considerations    ..
27
a.
The
Endangered
Species
Program         .
27
b.
General
Risk
Mitigation            ..
28
V.
What
Registrants
Need
to
Do                   
29
A.
Manufacturing
Use­
Products                 
31
1.
Additional
Generic
Data
Requirements         
31
2.
Labeling
for
Technical
and
Manufacturing­
Use
Products  ..
32
B.
End­
Use
Products                   
32
1.
Additional
Product
Specific
Data
Requirements    ..........
32
2.
Labeling
for
End­
Use
Products             ..
32
a.
Label
Changes
Summary
Table          .
34
VI.
Appendices                           .
36
A.
Table
of
Use
Patterns
for
Azadioxabicyclooctane        ..
37
B.
Table
of
Generic
Data
Requirements
and
Studies
Use
to
Make
the
Reregistration
Decision                 
39
C.
Technical
Support
Documents               ..
45
D.
Bibliography
Citations                   
47
E.
Generic
Data
Call­
In                    
53
F.
Product
Specific
Data
Call­
In                ..
54
G.
Batching
of
End­
Use
Products                
55
H.
List
of
All
Registrants
Sent
the
Data
Call­
In          
56
I.
List
of
Available
Forms                   
57
i
Azadioxabicyclooctane
Reregistration
Team
Health
Effects
Risk
Assessment
Timothy
Leighton
Timothy
McMahon
Talia
Milano
Bob
Quick
Cassi
Walls
Ecological
Risk
Assessment
Kathryn
Montague
Product
Chemistry
Najm
Shamim
Risk
Management
Ben
Chambliss
Tom
Luminello
ii
GLOSSARY
OF
TERMS
AND
ABBREVIATIONS
a.
i.
Active
Ingredient
aPAD
Acute
Population
Adjusted
Dose
ADTC
Antimicrobials
Division
Toxicology
Endpoint
Selection
Committee
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
iii
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
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
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)
iv
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
v
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
azadioxabicyclooctane
and
is
issuing
its
risk
management
decision.
The
Agency
has
decided
that
azadioxabicyclooctane
is
eligible
for
reregistration
provided
all
measures
outlined
in
this
document
are
implemented.
Azadioxabicyclooctane
consists
of
an
equilibrium
mixture
of
three
chemicals
(
I:
5­
hydroxymethoxymethyl­
1­
aza­
3,7­
dioxabicyclo(
3,3,0)
octane;
II:
5­
hydroxymethyl­
1­
aza­
3,7­
dioxabicyclo(
3,3,0)
octane;
III:
5­
hydroxypoly(
methyleneoxy
methyl­
1­
aza­
3,7­
dioxabicyclo(
3,3,0)
octane).
These
chemicals
cannot
be
divided
into
components
for
individual
testing
and
the
three
of
them
will
be
referred
to
as
azadioxabicyclooctane
in
this
Reregistration
Eligibilty
Decision.
This
mixture
is
registered
as
a
preservative
for
antimicrobial
control
in
the
following
use
sites:
oil
recovery
drilling
muds
and
flooding
fluids;
industrial
adhesives
and
coatings
(
natural
based
and
synthetic);
latex
and
polymer
emulsions;
metalworking
cutting
fluids;
latex
paints;
paper
coatings;
caulks
and
sealants;
inks;
pigment
dispersion
and
pigment
slurry;
and
textile
fiber
finishes
that
are
not
intended
as
clothing.
Azadioxabicyclooctane
has
been
cleared
by
the
US
Food
and
Drug
Administration
(
US
FDA)
for
use
as
an
antibacterial
preservative
in
paper
and
paperboard
products
that
are
limited
to
dry
food
contact
only
in
21CFR
176.180
as
well
as
a
component
in
paper
adhesives
in
21CFR
175.105.

Overall
Risk
Summary
The
Agency's
human
heath
risk
assessment
indicates
no
risks
of
concern
for
dietary
or
drinking
water
exposures.
Acute
and
chronic
dietary
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
general
U.
S.
population
and
all
population
subgroups.

Azadioxabicyclooctane
is
not
likely
to
contaminate
surface
and
ground
waters
based
on
its
use
patterns.
Thus,
a
drinking
water
assessment
was
not
conducted.

Residential
risks
for
handlers
were
calculated
for
short­
and
intermediate­
term
dermal
and
inhalation
exposures.
All
exposure
and
risk
estimates
for
residential
handler
scenarios
are
below
the
Agency's
level
of
concern
with
the
exception
of
the
risks
associated
with
application
of
paint
using
an
airless
sprayer
at
the
maximum
application
rate.
Based
on
the
use
patterns
of
azadioxabicyclooctane
there
are
no
potential
dermal
post
application
exposures
to
assess.
Inhalation
post
application
exposures
are
expected
to
be
minimal
because
the
paint
is
dry
and
the
vapor
pressure
of
azadioxabicyclooctane
is
negligible.

For
the
occupational
handler
dermal
and
inhalation
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
were
above
target
MOEs
for
all
scenarios.
Post­
application
exposure
is
expected
to
be
minimal
based
on
the
use
patterns
of
this
chemical
with
the
exception
of
metal
working
fluids.
Occupational
risks
from
post­
application
exposure
were
calculated
for
long­
term
dermal
and
inhalation
exposures
to
machinists
resulting
from
metal
working
fluid
use.
Risks
of
concern
were
identified
for
this
use
pattern
at
the
maximum
application
rate
of
0.3%
product
by
weight
of
material
treated.
vi
The
indoor
uses
of
azadioxabicyclooctane
are
not
likely
to
pose
risk
to
fish,
wildlife
or
plants
due
to
the
low
likelihood
of
exposure
and
the
low
toxicity
of
the
compound.
The
offshore
oil
production
use
drilling
fluid
treatment
and
flooding
fluid
treatment
is
considered
unlikely
to
adversely
affect
aquatic
organisms
due
to
the
low
toxicity
and
large
dilution
factor.
The
Agency
assumes
that
the
waste
streams
occurring
from
terrestrial
oil
production
are
actively
managed
under
local
environmental
regulations
to
prevent
adverse
ecological
effects.

Dietary
Risk
The
Agency
has
conducted
a
dietary
exposure
and
risk
assessment
for
use
of
azadioxabicyclooctane
as
a
preservative
in
paper
coatings
and
paper
adhesives
each
of
which
may
end
in
indirect
food
contact
scenarios.
For
both
the
acute
and
chronic
dietary
exposure,
the
risk
is
highest
for
children
(
12%
of
the
acute
PAD
and
39.6%
chronic
PAD).
For
an
adult,
the
acute
and
chronic
dietary
exposures
are
5.1%
and
17%
of
the
acute
and
chronic
PADs
respectively.
All
dietary
exposures
calculated
are
below
the
Agency's
level
of
concern
(
100%
of
aPAD
or
cPAD)
for
non­
cancer
risk.
A
dietary
cancer
risk
assessment
could
not
be
performed
as
there
are
no
carcinogenicity
data
for
azadioxabicyclooctane.

Drinking
Water
Risk
None
of
the
uses
associated
with
azadioxabicyclooctane
are
expected
to
impact
either
surface
or
ground
water
resources.
Therefore,
no
drinking
water
assessment
was
performed.

Residential
Handler
Risk
Residential
risks
for
handlers
were
calculated
for
short­
and
intermediate­
term
dermal
and
inhalation
exposures.
All
exposure
and
risk
estimates
for
residential
handler
scenarios
are
below
the
Agency's
level
of
concern
with
the
exception
of
the
risks
associated
with
application
of
paint
using
an
airless
sprayer
at
the
maximum
application
rate.

Aggregate
Risk
The
aggregate
short­
term
risk
assessment
is
designed
to
provide
estimates
of
risk
likely
to
result
from
exposures
to
the
pesticide
or
pesticide
residues
in
food,
water,
and
from
residential
(
or
other
non­
occupation)
pesticide
uses.
For
adults,
the
aggregate
assessment
includes
dietary
(
oral)
and
residential
inhalation
exposures
from
painting.
An
assessment
was
not
conducted
for
children
since
there
are
no
residential
exposures
expected
for
this
subgroup.

Since
exposures
to
residential
handlers
for
the
paint
scenario
are
of
concern
at
the
highest
application
rate,
short­
term
aggregate
risks
are
also
of
concern.

Occupational
Risk
The
short­
and
intermediate­
term
exposure
scenarios
identified
for
occupational
workers
are
the
liquid
pour
and
liquid
pump
applications
of
this
chemical
when
it
is
used
as
a
preservative
for
the
label­
specified
materials.
There
are
also
occupational
painter
scenarios
(
which
result
from
the
chemical
being
incorporated
as
a
preservative
into
paints)
that
involve
the
vii
methods
of
applications
of
airless
painting
and
brush
painting.
All
exposure
and
risk
estimates
for
occupational
handler
scenarios
are
below
the
Agency's
level
of
concern.
Therefore,
no
risk
mitigation
measures
are
required
for
these
handler
scenarios.

For
azadioaxabicyclootane,
exposures
are
expected
to
be
minimal
except
for
the
metal
working
fluid
scenario.
Occupational
risks
from
post­
application
exposure
were
calculated
for
long­
term
dermal
and
inhalation
exposures
to
machinists
resulting
from
metal
working
fluid
use.
Risks
of
concern
were
identified
for
this
use
pattern
at
the
maximum
application
rate
of
0.3%
product
by
weight
of
material
treated.

Ecological
Risk
The
indoor
uses
of
azadioxabicyclooctane
are
not
likely
to
pose
risk
to
fish,
wildlife
or
plants
due
to
the
low
likelihood
of
exposure
and
the
low
toxicity
of
the
compound.
Most
uses
of
azadioxabicyclooctane
are
indoor
uses,
with
little
chance
of
exposure
to
the
environment.
The
oil
production
uses
do
occur
outdoors;
however,
the
Agency
does
not
have
an
available
model
for
estimating
exposure
from
those
uses.
The
risk
from
offshore
oil
drilling
uses
of
azadioxabicyclooctane
was
previously
addressed
(
Agency
review
July
14,
1983),
and
the
application
of
500­
2000
ppm
drilling
fluid
treatment
or
100­
1000
ppm
flooding
fluid
treatment
was
considered
A
unlikely
to
adversely
affect
aquatic
organisms
due
to
the
low
toxicity
and
large
dilution
factor.@
Discharge
of
waste
streams
occurring
from
terrestrial
oil
recovery
operations
would
be
regulated
at
the
local
level
in
order
to
prevent
undue
environmental
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
azadioxabicyclooctane.
The
Agency
is
issuing
this
RED
for
azadioxabicyclooctane,
as
announced
in
a
Notice
of
Availability
published
in
the
Federal
Register.
This
RED
document
includes
guidance
and
time
frames
for
making
any
necessary
label
changes
for
products
containing
azadioxabicyclooctane.

Summary
of
Mitigation
Measures
The
Agency
has
determined
that
azadioxabicyclooctane
is
eligible
for
reregistration
provided
the
mitigation
measures
described
in
this
document
and
the
label
changes
included
in
Table
13
in
Section
V
of
the
RED
are
implemented.

Residential:

To
reduce
residential
exposure,
the
Agency
has
determined
that
the
following
mitigation
and
label
changes
for
specific
scenarios
are
appropriate
and
required
for
reregistration
eligibility:

 
Reduce
the
maximum
application
rate
for
paint
uses
to
0.4%
product
by
weight
of
material
treated.
viii
Occupational:

To
reduce
post­
application
exposure,
the
Agency
has
determined
that
the
following
mitigation
and
label
changes
for
specific
scenarios
are
appropriate
and
required
for
reregistration
eligibility:

 
Reduce
the
maximum
application
rate
for
paint
uses
to
0.2%
product
by
weight
of
material
treated.

Data
Requirements
Confirmatory
data
is
required
to
complete
the
reregistration
of
azadioxabicyclooctane
as
outlined
in
Section
V
of
this
document.
A
complete
list
of
data
gaps
is
presented
in
Appendix
B
(
Table
of
Generic
Data
Requirements)
as
well
as
in
Appendix
E
(
the
Generic
Data
Call­
In)
at
the
end
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
azadioxabicyclooctane.

Azadioxabicyclooctane
is
a
materials
preservative
registered
for
use
on
oil
recovery
drilling
muds
and
flooding
fluids;
industrial
adhesives
and
coatings
(
natural
based
and
synthetic);
latex
and
polymer
emulsions;
metalworking
cutting
fluids;
latex
paints;
paper
coatings;
caulks
and
sealants;
inks;
pigment
dispersion
and
pigment
slurry;
and
textile
fiber
finishes
that
are
not
intended
as
clothing.

The
Agency
has
concluded
that
the
FQPA
safety
factor
should
be
retained
at
10X.
The
toxicology
database
is
not
complete
with
respect
to
assessing
the
increased
susceptibility
to
infants
and
children
as
required
by
FQPA
for
azadioxabicyclooctane.
There
is
an
absence
of
adequate
developmental
toxicity
data
and
an
absence
of
reproductive
toxicity
data
for
this
chemical.
There
is
one
prenatal
dermal
developmental
toxicity
study
available
for
azadioxabicyclooctane.
While
the
developmental
study
showed
no
evidence
of
susceptibility
of
offspring,
the
dermal
route
of
administration
is
not
a
good
indicator
of
potential
effects
from
oral
exposures
and
the
available
data
do
not
examine
potential
reproductive
effects
of
the
chemical.

Risks
summarized
in
this
document
are
those
that
result
only
from
the
use
of
the
active
ingredient
azadioxabicyclooctane.
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
2
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
azadioxabicyclooctane
and
any
other
substances.
Azadioxabicyclooctane
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
action,
therefore,
EPA
has
not
assumed
that
azadioxabicyclooctane
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
azadioxabicyclooctane.
In
an
effort
to
simplify
the
RED,
the
information
presented
herein
is
summarized
from
more
detailed
information
which
can
be
found
in
the
technical
supporting
documents
for
azadioxabicyclooctane
referenced
in
this
RED.
The
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
azadioxabicyclooctane,
and
its
regulatory
history.
Section
III,
Summary
of
azadioxabicyclooctane
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
Azadioxabicyclooctane
has
been
registered
since
October
30,
1975.
The
registration
and
all
data
to
support
reregistration
were
transferred
from
Tenneco
Chemicals
on
December
22,
1982
to
Nuodex
Inc.
The
Nuosept
95
product
was
purchased
by
International
Specialty
Products
on
March
26,
2002.
There
are
currently
two
products
registered
with
azadioxabicyclooctane
as
the
active
ingredient
(
one
technical
product
and
one
end­
use­
product).

B.
Chemical
Identification
1.
Technical
Azadioxabicyclooctane
5
9
7
2
0
­
4
2
2
O
N
O
O
OH
6
5
4
2
­
3
7
­
6
N
O
O
OH
Azadioxabicyclooctane
is
an
equilibrium
reaction
mixture
of
three
Azadioxabicyclooctanes
in
a
50%
aqueous
solution.

Common
name:
Azadioxabicyclooctane
Chemical
names:
5­
Hydroxymethoxymethyl­
1­
aza­
3,7­
dioxabicyclo(
3,3,0)
octane;
5­
Hydroxymethyl­
1­
aza­
3,7­
dioxabicyclo(
3,3,0)
octane;
5­
Hydroxypoly(
methylene­
oxy)*
methyl­
1­
aza­
3,
7­
dioxabicyclo(
3.3.0)
octane
*(
74%
C2,
21%
C3,
4%
C4,
1%
C5)
4
CAS
Registry
No.:
107001:
59720­
42­
2
107002:
6542­
37­
6
107003:
56709­
13­
8
OPP
Chemical
Code:
107001,
107002,
107003
Case
Number:
3023
Chemical
Family:
Bicyclic
Oxazolidine
Empirical
formula:
C7H13O4N
Molecular
weight:
170.5
Trade
name:
Nuosept
95
Preservative
Basic
manufacturer:
International
Specialty
Products
Technical
azadioxabicyclooctane
is
in
the
form
of
a
liquid
and
is
clear
yellow
in
color.
The
solubility
of
azadioxabicyclooctane
in
organic
solvents
range
from
0.2
g/
100
g
at
25oC
(
Hexane)
to
28.0
g/
100
g
at
25oC
(
Ethyl
ether).
Azadioxabicyclooctane
has
a
vapor
pressure
of
20.44
mm
Hg
at
90
oC
and
<
2.1
x
10­
5
mm
Hg
at
20oC.

C.
Use
Profile
The
following
is
information
on
the
currently
registered
uses
of
azadioxabicyclooctane
and
an
overview
of
use
sites
and
application
methods.
A
detailed
table
of
the
uses
of
azadioxabicyclooctane
eligible
for
reregistration
is
contained
in
Appendix
A.

Type
of
Pesticide:
Preservative
Summary
of
Use:

Food:
Paper
coatings
and
paper
adhesives.

Non­
Food:
Adhesives
(
natural
and
synthetic),
caulks,
metalworking
fluids,
drilling
muds
and
flooding
fluids,
paper
coatings,
latex
emulsions,
wax
emulsions.
Latex
paint,
inks,
pigment
dispersion,
pigment
slurry,
sealants,
textile
fiber
finishes.

Residential:
Paints
and
caulks.

Target
Pests:
Used
to
control
slime
forming
bacteria
and
fungi.

Formulation
Types:
The
end­
use
product
is
a
liquid.

Method
and
Rates
of
Application:
5
Equipment:
Open
pour,
liquid
pump.

Application
Rates:
0.05
to
0.5
percent
by
weight.

Timing:
Added
to
water
phase
or
post
addition
during
manufacturing
process.
6
III.
Summary
of
Azadioxabicyclooctane
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
azadioxabicyclooctane.
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/
dockets.
Hard
copies
of
these
documents
may
be
found
in
the
OPP
public
docket
under
docket
number
OPP­
2005­
0186.
The
OPP
public
docket
is
located
in
Room
119,
Crystal
Mall
II,
1801
S.
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
Azadioxabicyclooctane
A
brief
overview
of
the
toxicity
studies
used
for
determining
endpoints
in
the
dietary
risk
assessments
are
outlined
in
Table
2.
Further
details
on
the
toxicity
of
azadioxabicyclooctane
can
be
found
in
the
azadioxabicyclooctane
docket
and
include,
"
AD
Preliminary
Risk
Assessment
for
the
Reregistration
Eligibility
Decision"
dated
September
28,
2005;
and
"
Report
of
the
Antimicrobials
Division
Toxicology
Endpoint
Selection
Committee",
dated
April
20,
2005.
These
documents
are
available
on
the
Agency's
website
in
the
EPA
Docket
at
http://
www/
epa.
gov/
edockets.

The
Agency
has
reviewed
all
toxicity
studies
submitted
for
azadioxabicyclooctane
and
has
determined
that
the
toxicological
database
is
sufficient
for
reregistration.
Major
features
of
the
toxicology
profile
are
presented
below.
The
acute
oral
and
dermal
toxicities
of
azadioxabicyclooctane
are
low.
The
acute
inhalation
toxicity
showed
a
median
lethal
dose
range
of
between
0.441
mg/
L
and
0.819
mg/
L
in
males,
and
between
0.819
mg/
L
and
1.397
mg/
L
in
females,
with
epistaxis,
labored
breathing,
rales,
and
rhinorrhea
in
all
dose
groups.
Corneal
opacity
was
observed
in
the
primary
eye
irritation
study
resulting
in
a
Toxicity
Category
I
classification.
Moderate
dermal
irritation
effects
were
noted
in
the
primary
dermal
irritation
study,
leading
to
a
Toxicity
category
III
classification.

Table
1.
Acute
Toxicity
Profile
for
Azadioxabicyclooctane
Guideline
Number
Study
Type/
Test
substance
(%
a.
i.)
MRID
Number/
Citation
Results
Toxicity
Category
870.1100
(
§
81­
1)
Acute
Oral­
Rat
Nuosept
®
95
(
50%
a.
i.)
MRID
41641601
LD50
=
1940
mg/
kg/
day
III
870.1200
(
§
81­
2)
Acute
Dermal­
Rabbit
Nuosept
®
95
(
50%
a.
i.)
MRID
41671801
LD50
>
2000
mg
/
kg
III
870.1300
(
§
81­
3)
Acute
Inhalation­
Rat
Nuosept
®
95
(
50%
a.
i.)
MRID
42650901
Combined
LC50
 
>
0.441
mg/
L<
0.819
mg/
L
II
7
Guideline
Number
Study
Type/
Test
substance
(%
a.
i.)
MRID
Number/
Citation
Results
Toxicity
Category
870.2400
(
§
81­
4)
Primary
Eye
Irritation­
Rabbit
Nuosept
®
95
(
50%
a.
i.)
MRID
41641602
Corrosive
I
870.2500
(
§
81­
5)
Primary
Dermal
Irritation­
Rabbit
Nuosept
®
95
(
50%
a.
i.)
MRID
41641603
Moderate
irritant
III
870.2600
(
§
81­
6)
Dermal
Sensitization
NA
Assumed
Sensitizer
no
data
available
The
doses
and
toxicological
endpoints
selected
for
the
dietary
exposure
scenarios
are
summarized
in
Table
2.

Table
2.
Toxicological
Endpoints
for
Azadioxabicyclooctane
(
Dietary)

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
gen.
pop.)
NOAEL
=
10.6
mg/
kg/
day
UF
=
100
FQPA
SF
=
10x
aPAD
=
acute
RfD
FQPA
SF
=
0.01
mg/
kg/
day
90
day
oral
toxicity
in
rats
NOAEL
=
10.6
mg/
kg/
day
based
on
decreased
water
consumption
at
56.5
mg/
kg/
day
in
males.

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

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

Cancer
(
oral)
No
cancer
data
available
Notes:
UF
=
uncertainty
factor,
FQPA
SF
=
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,
LOC
=
level
of
concern
8
From
the
available
repeat
dose
toxicity
studies,
there
was
no
evidence
of
neurotoxicity
of
azadioxabicyclooctane.
There
are
no
reproductive
toxicity
data
available
for
azadioxabicyclooctane.

In
a
dermal
developmental
toxicity
study
there
was
clear
evidence
of
maternal
dermal
effects
(
e.
g.
erythema,
scabbing,
edema)
in
all
treatment
groups.
The
LOAEL
for
maternal
dermal
toxicity
is
100
mg/
kg/
day
(
based
on
severe
dermal
irritation);
a
NOAEL
could
not
be
established.
The
systemic
maternal
toxicity
NOAEL
is
greater
than
or
equal
to
1000
mg/
kg/
day.
There
were
no
other
embryotoxic
or
fetotoxic
effects
observed
in
this
study.
The
developmental
NOAEL
is
greater
than
or
equal
to
1000
mg/
kg/
day.

Carcinogenicity
Classification
There
are
no
lifetime
carcinogenicity
studies
available
for
azadioxabicyclooctane.

Mutagenicity
Azadioxabicyclooctane
has
been
tested
for
mutagenic
activity
in
several
assays.
Although
the
data
suggest
largely
negative
responses,
the
lack
of
test
article
characterization
(
especially
in
light
of
positive
responses
observed
in
two
studies)
points
to
the
need
for
proper
test
article
characterization
before
an
adequate
conclusion
can
be
made
about
the
mutagenicity
of
azadioxabicyclooctane.

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,
azadioxabicyclooctane
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
for
certain
exposure
pathways.
The
FQPA
Safety
Factor
has
been
retained
(
i.
e.,
remains
10X)
for
azadioxabicyclooctane
based
on
the
very
limited
developmental
and
reproductive
toxicity
databases.

The
toxicology
database
for
azadioxabicyclooctane
with
respect
to
assessing
sensitivity
of
infants
and
children
is
not
complete.
There
is
only
one
study,
a
developmental
toxicity
study
in
rats
conducted
by
the
dermal
route,
available
for
this
chemical.
While
the
developmental
study
showed
no
evidence
of
susceptibility
of
offspring
to
this
chemical,
the
route
of
administration
is
not
a
good
indicator
of
potential
effects
from
oral
exposures.
9
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
azadioxacyclooctane
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
(
0.1
mg/
kg/
day)
modified
by
the
FQPA
safety
factor.
The
acute
reference
dose
was
derived
from
a
90­
day
oral
toxicity
study
in
rats
in
which
both
the
NOAEL
(
10.6
mg/
kg/
day)
and
the
LOAEL
(
56.5
mg/
kg/
day)
were
determined.
The
azadioxacyclooctane
aPAD
is
0.01
mg/
kg/
day
based
on
a
reference
dose
of
0.1
mg/
kg/
day,
and
incorporating
the
FQPA
safety
factor
of
10X
for
the
overall
U.
S.
population
or
any
population
subgroups.

b.
Chronic
PAD
Chronic
dietary
risk
for
azadioxacyclooctane
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
(
0.03
mg/
kg/
day)
modified
by
the
FQPA
safety
factor.
The
cPAD
was
derived
from
a
90­
day
oral
toxicity
study
in
rats
in
which
both
the
NOAEL
(
10.6
mg/
kg/
day)
and
the
LOAEL
(
56.5
mg/
kg/
day)
were
determined.
However,
no
chronic
studies
were
available
necessitating
the
use
of
an
additional
3X
uncertainty
factor.
The
azadioxacyclooctane
cPAD
is
0.003
mg/
kg/
day
based
on
a
reference
dose
of
0.03
mg/
kg/
day,
which
includes
the
incorporation
of
the
FQPA
safety
factor
(
10X)
for
the
overall
U.
S.
population
or
any
population
subgroups.

4.
Exposure
Assumptions
The
use
of
antimicrobial
chemicals
on
paper
coatings
and
paper
adhesives
may
result
in
pesticide
residues
in
human
food.
The
Agency
must
determine
the
risk
to
human
health
that
may
occur
from
exposure
to
these
chemicals.

Potential
dietary
exposures
to
the
active
ingredient,
azadioxabicyclooctane,
from
its
uses
as
paper
coating
and
paper
adhesive
preservatives
were
assessed.
Azadioxabicyclooctane
has
been
cleared
by
the
US
Food
and
Drug
Administration
(
US
FDA)
for
use
as
an
antibacterial
preservative
in
paper
and
paperboard
products
contacting
dry
food
only
in
21CFR176.180
as
well
as,
a
component
in
paper
adhesives
in
21CFR175.105.

US
FDA
has
estimated
a
Cumulative
Dietary
Concentration
of
12
ppb
and
a
Cumulative
Dietary
Exposure
Intake
(
CEDI)
of
0.006
mg/
kg/
day
for
azadioxabicyclooctane
(
http://
www.
cfsan.
fda.
gov/~
dms/
opa­
tedi.
html)
however,
the
Agency
does
not
have
the
specific
details
(
i.
e.,
application
rates
or
residue
migration
potential)
used
by
US
FDA
in
their
review
of
this
petition.
Furthermore,
no
residue
data
have
been
submitted
to
the
Agency
in
support
of
the
10
azadioxabicyclooctane
indirect
food
contact
uses.
Therefore,
a
screening­
level
assessment
has
been
conducted
using
the
US
FDA's
Center
for
Food
Safety
&
Applied
Nutrition's
(
CFSAN)
approach
as
presented
in
"
Preparation
of
Food
Contact
Notifications
and
Food
Additive
Petitions
for
Food
Contact
Substances:
Chemistry
Recommendations"
dated
April
2002.
The
Agency
calculated
"
worst­
case"
dietary
concentration
values
using
the
labeled
maximum
application
rate
for
the
paper
coating
preservative
use
(
0.25%
or
2500
ppm
of
the
paper
coating)
(
EPA
Reg.
No.
1529­
28),
US
FDA's
default
assumptions
for
preservation
of
paper
adhesives,
and
EPA's
standard
values
for
body
weights.

Since
azadioxabicyclooctane
can
be
used
as
a
preservative
in
paper
coatings
and
adhesives,
the
dietary
exposures
resulting
from
both
uses
must
be
added
together
because
both
the
coatings
and
adhesives
could
be
used
together
within
one
paper
product.

5.
Dietary
(
Food)
Risk
Assessment
Generally,
a
dietary
risk
estimate
that
is
less
than
100%
of
the
acute
or
chronic
PAD
does
not
exceed
the
Agency's
risk
concerns.
A
summary
of
acute
and
chronic
risk
estimates
are
shown
in
Table
3.

a.
Acute
Dietary
Risk
An
acute
dietary
risk
assessment
was
conducted
for
azadioxabicyclooctane
food
uses.
The
result
of
the
combined
assessment
for
coatings
and
adhesives
showed
the
risk
estimates
to
be
<
12.0%
of
the
aPAD
for
all
population
subgroups
and
therefore
are
not
of
concern.

b.
Chronic
(
Non­
cancer)
Dietary
Risk
A
chronic
dietary
risk
assessment
was
conducted
for
azadioxabicyclooctane
food
uses.
The
risk
analysis
assumes
daily
exposure
from
paper
coatings
and
adhesives.
The
result
of
the
combined
assessment
for
coatings
and
adhesives
showed
the
risk
estimates
to
be
<
39.6%
of
the
cPAD
for
all
population
subgroups
and
therefore
are
not
of
concern.

Table
3:
Acute
and
Chronic
Dietary
Exposure
and
Risk
Use
Daily
Dietary
Dose
(
mg/
kg
bw/
day)
%
aPAD
%
cPAD
Paper
Coating
Preservative
0.00021
(
adult)
0.0005
(
child)
2.1%
(
adult)
5%
(
child)
7.0%
(
adult)
16.6%
(
child)
Paper
Adhesive
Preservative
0.00030
(
adult)
0.00070
(
child)
3%
(
adult)
7%
(
child)
10%
(
adult)
23%
(
child)
Combined
0.00051
(
adult)
0.0012
(
child)
5.1%
(
adult)
12%
(
child)
17%
(
adult)
39.6%
(
child)
11
c.
Dietary
Risk
from
Drinking
Water
Azadioxabicyclooctane
is
not
likely
to
contaminate
surface
and
ground
waters
based
on
its
use
patterns.
Therefore,
a
drinking
water
assessment
was
not
conducted.

6.
Residential
Exposure
Residential
exposure
assessment
considers
all
potential
pesticide
exposure,
other
than
exposure
due
to
residues
in
food
or
in
drinking
water.
Exposure
may
occur
during
painting
or
caulking.
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
NOAEL.
Based
on
its
use
patterns,
azadioxabicyclooctane
has
been
assessed
for
the
residential
mixing/
loading/
applicator
(
or
"
handler")
exposure
for
applications
by
homeowners
painting.
For
azadioxabicyclooctane
there
are
no
potential
dermal
post
application
exposures
to
assess.
As
for
inhalation
post
application
exposures,
these
are
expected
to
be
minimal
because
the
paint
is
dry
and
the
vapor
pressure
of
azadioxabicyclooctane
is
negligible.

a.
Toxicity
The
toxicological
endpoints
and
associated
uncertainty
factors
used
for
assessing
the
nondietary
risks
for
azadioxabicyclooctane
are
listed
in
Table
4.

A
MOE
greater
than
or
equal
to
3,000
is
considered
adequately
protective
for
the
residential
exposure
assessment
for
the
inhalation
route
of
exposure.
The
MOE
of
3,000
includes
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variation,
3x
for
a
lack
of
histopathology
data
and
the
10x
FQPA
factor.
The
FQPA
10x
hazard
based
safety
factor
was
retained
based
on
the
lack
of
developmental
and
reproductive
toxicity
data
for
azadioxabicyclooctane,
but
was
not
applied
to
children's
risk
assessments
for
residential
exposure
as
residential
exposures
to
children
are
not
expected
from
the
uses.

For
the
dermal
route
of
exposure,
a
MOE
greater
than
or
equal
to
300
is
considered
adequately
protective
for
the
residential
exposure
assessment.
The
MOE
of
300
includes
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variation
and
3x
for
lack
of
a
NOAEL.

A
MOE
greater
than
or
equal
to
3,000
is
considered
adequately
protective
for
the
longterm
occupational
exposure
assessment
for
the
dermal
route
of
exposure.
The
MOE
of
3000
includes
10x
for
interspecies
extrapolation,
10x
for
intraspecies
variation
and
3x
for
lack
of
a
NOAEL
and
3x
for
the
lack
of
a
chronic
endpoint.

Table
4:
Toxicity
Endpoints
Selected
for
Assessing
Occupational
and
Residential
Risk
for
Azadioxabicyclooctane
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Dermal
(
all
Dermal
LOAEL
=
Occupational
MOE
=
Co­
critical
studies:
12
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
durations)
100
mg/
kg/
day
300
(
ST
and
IT)
=
3000
(
LT)

Residential
MOE
=

300
(
ST
and
IT)
21­
day
dermal
toxicity
in
rabbits
LOAEL
=
100
mg/
kg/
day
(
severe
dermal
effects)

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

Inhalation
(
all
durations
)
NOAEL=
10.6
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Occupational
MOE
=
300
Residential
MOE
=
3000
90
day
oral
toxicity
in
rats
NOAEL
=
10.6
mg/
kg/
day
based
on
decreased
water
consumption
at
56.5
mg/
kg/
day
in
males.

Cancer
No
cancer
data
available
Notes:
ST=
short­
term,
IT
=
intermediate 
term,
LT=
long­
term
b.
Residential
Handler
i.
Exposure
Scenarios,
Data
and
Assumptions
Residential
exposure
may
occur
for
azadioxabicyclooctane
during
application
as
a
paint
or
caulk.
A
number
of
assumptions,
or
estimates,
such
as
adult
body
weight
and
area
treated
per
application,
are
made
by
the
Agency
for
residential
risk
assessment.
Also,
note
that
residential
handlers
are
sometimes
addressed
somewhat
differently
than
occupational
handlers
in
that
homeowners
are
assumed
to
complete
all
elements
of
an
application
(
mix/
load/
apply)
without
the
use
of
personal
protective
equipment.

The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
these
scenarios:

(
1)
painting
using
a
brush
or
roller,
(
2)
painting
using
an
airless
sprayer
Based
on
end­
use
product
application
methods
and
use
amounts,
it
is
assumed
that
exposures
while
applying
paints
will
be
equal
to
or
greater
than
exposures
that
may
occur
when
an
individual
uses
any
of
the
other
end
use
products
(
i.
e.,
caulks,
inks,
sealants).
Therefore,
residential
handler
exposures
were
assessed
for
the
application
of
paint,
as
this
scenario
represents
maximum
possible
exposure
to
the
chemical.

Brush/
Roller
The
dermal
and
inhalation
unit
exposures
for
this
application
method
were
obtained
from
13
the
Agency's
Residential
SOPs.
The
dermal
unit
exposure
is
representative
of
the
handler
a
teeshirt
and
shorts
while
applying
the
paint
with
a
brush
and
without
gloves
because
this
is
a
residential
use
site.
The
inhalation
unit
exposure
is
representative
of
a
painter
applying
paint
with
a
brush.
The
maximum
application
rate
is
0.5%
product
by
weight
of
material
being
treated.
The
application
rates
on
the
label
do
not
account
for
the
product
containing
only
50%
a.
i.,
so
the
maximum
application
results
in
exposure
to
0.25%
a.
i.
by
weight
of
the
material
treated.

For
this
scenario,
the
painter
is
expected
to
handle
2
gallons
of
paint
per
day.
This
is
from
the
AD
Residential
SOPs
(
1997
&
2001)
in
which
this
value
is
the
90th
percentile
value
of
8
gallons
of
latex
paint
used
per
year
divided
by
the
mean
frequency
of
4
painting
events
per
year.
The
density
of
paint
is
assumed
to
be
10
lb/
gallon,
so
that
the
value
of
2
gallons
is
equivalent
to
20
pounds
of
paint.

Airless
Sprayer
The
dermal
and
inhalation
unit
exposures
for
this
application
method
were
obtained
from
the
Agency's
Residential
SOPs.
The
dermal
unit
exposure
is
representative
of
the
handler
wearing
a
tee­
shirt
and
shorts
while
performing
an
ungloved
airless
spray
application.
The
inhalation
unit
exposure
is
representative
of
a
painter
applying
a
material
with
an
airless
sprayer.
For
this
scenario,
the
painter
is
expected
to
handle
15
gallons
of
paint
per
day.
This
is
from
the
Agency's
SOP's
in
which
this
value
is
based
on
coverage
of
200ft2/
gal
and
a
house
size
being
40'
x
30'
x
20'
(
surface
area
of
2,800ft2).
The
density
of
paint
is
assumed
to
be
10
lbs/
gallon,
so
that
the
value
of
15
gallons
is
equivalent
to
150
lbs
of
paint.

ii.
Residential
Handler
Risk
Estimates
Based
on
toxicological
criteria
and
potential
for
exposure,
the
Agency
has
conducted
dermal
and
inhalation
exposure
assessments.
As
noted
previously,
MOEs
greater
than
or
equal
to
3,000
for
the
inhalation
route
of
exposure
and
300
for
dermal
exposure
are
considered
adequately
protective
for
the
residential
exposure
assessment.

A
summary
of
the
residential
handler
exposures
and
risk
are
presented
on
Table
5.
For
residential
handlers
that
handle
products
containing
azadioxabicyclooctane,
short­
term,
and
intermediate­
term
MOEs
were
below
the
target
MOEs
for
painting
using
an
airless
sprayer
at
the
maximum
application
rate
and
thus
are
of
concern.
MOEs
do
not
exceed
the
Agency's
level
of
concern
for
the
painting
using
a
brush
or
roller
or
for
painting
using
an
airless
sprayer
at
the
minimum
application
rate.
14
Table
5:
Estimates
of
Exposures
and
Risks
to
Residential
Handlers
of
Azadioxabicyclooctane
(
Short
­
Term
Duration)

Daily
Dose
(
mg
a.
i./
kg
per
day)
MOE
Exposure
Scenario
Method
of
Application
Application
rate
(%
a.
i.
by
weight
of
material
being
treated
=
%
product
by
weight
of
material
treated
x
50%
a.
i.)
Dermal
Dose
Inhalation
Dose
Dermal
(
target
=
300)
Inhalation
(
target
=
3000)

Brush/
Roller
0.25%
(
max)
0.1643
0.0002
609
53,000
Airless
Sprayer
0.25%
(
max)
0.4232
0.004446
236
2.400
Paints
Airless
Sprayer
0.05%
(
min)
i
0.0846
0.000889
1,181
12,000
c.
Residential
Post­
Application
Residential
post
application
exposures
occur
when
bystanders
contact
areas
in
which
the
antimicrobial
end
use
product
has
recently
been
applied.
For
azadioxabicyclooctane
there
are
no
potential
dermal
post
application
exposures
to
assess.
As
for
inhalation
post
application
exposures,
these
are
expected
to
be
minimal
because
the
paint
is
dry
and
the
vapor
pressure
of
azadioxabicyclooctane
is
negligible.

6.
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.
Since
no
drinking
water
estimates
were
developed
for
azadioxabicyclooctane,
aggregate
assessments
include
exposure
to
food
and
as
a
result
of
residential
uses
only.

Typically,
aggregate
risk
assessments
are
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
6
months
to
lifetime)
exposures.
However,
acute
and
chronic
aggregate
assessments
were
not
conducted
because
there
are
no
significant
impacts
to
drinking
water
sources,
nor
are
there
long­
term
residential
uses.
Thus,
only
short­
and
intermediate­
term
aggregate
assessments
were
conducted.
Oral
and
inhalation
exposure
and
risk
estimates
were
combined
for
the
aggregate
risk
assessment
because
these
endpoints
are
based
on
the
same
toxicity
study
and
effects
of
concern.
Dermal
exposures
were
not
aggregated
with
the
oral
or
inhalation
exposures
due
to
different
toxicological
endpoints
for
oral
and
dermal
exposures.

a.
Short­
Term
Aggregate
Risk
The
aggregate
short­
term
risk
assessment
is
designed
to
provide
estimates
of
risk
likely
to
result
from
exposures
to
the
pesticide
or
pesticide
residues
in
food,
water,
and
from
residential
15
(
or
other
non­
occupation)
pesticide
uses.
For
adults,
the
aggregate
assessment
includes
dietary
(
oral)
and
residential
inhalation
exposures
from
painting.
An
assessment
was
not
conducted
for
children
since
there
are
no
residential
exposures
expected
for
this
subgroup.

Since
exposures
to
residential
handlers
for
the
paint
scenario
are
of
concern
at
the
highest
application
rate
short­
term
aggregate
risks
are
also
of
concern.

7.
Occupational
Exposure
and
Risk
Workers
can
be
exposed
to
a
pesticide
through
mixing,
loading,
and/
or
applying
a
pesticide,
or
re­
entering
treated
sites.
Occupational
handlers
of
azadioxabicyclooctane
include
workers
in
a
variety
of
occupational
settings.
Additionally,
postapplication
exposures
are
likely
to
occur
in
these
settings.
The
representative
scenarios
selected
for
assessment
were
evaluated
using
maximum
application
rates
as
recommended
on
the
product
labels
for
azadioxabicyclooctane.

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.

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
for
azadioxabicyclooctane,
MOEs
greater
than
300
for
dermal
and
inhalation
exposures
are
not
of
concern
to
the
Agency
for
short­
and
intermediate­
term
exposures.
MOEs
greater
than
1000
for
dermal
and
inhalation
exposures
are
not
of
concern
to
the
Agency
for
long­
term
exposures.
For
workers
entering
a
treated
site,
MOEs
are
calculated
for
each
day
after
application
to
determine
the
minimum
length
of
time
required
before
workers
can
safely
re­
enter.

a.
Occupational
Toxicity
Table
4
provides
a
listing
of
the
toxicological
endpoints
used
in
the
occupational
risk
assessment
for
azadioxabicyclooctane.

b.
Occupational
Handler
Exposure
The
Agency
has
determined
that
there
is
potential
for
dermal
and
inhalation
worker
exposure
to
azadioxabicyclooctane
at
various
use
sites
when
used
as
a
preservative
consistent
with
existing
labeling.
There
are
also
occupational
painter
scenarios
associated
with
its
use
as
a
preservative
in
paints.
Painting
methods
evaluated
include
application
with
an
airless
sprayer
and
a
brush.
To
assess
handler
risks,
the
Agency
used
surrogate
unit
exposure
data
from
both
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
proprietary
data
from
the
Chemical
Manufacturers
(
CMA)
antimicrobial
exposure
study.
16
c.
Occupational
Handler
Risk
Summary
For
the
occupational
handler
dermal
and
inhalation
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
were
above
the
target
MOEs
for
all
scenarios
(
i.
e.,
dermal
and
inhalation
>
300).
However,
the
inhalation
MOE
for
the
airless
sprayer
paint
scenario
falls
below
the
MOE
of
1,000,
when
the
additional
10X
route­
to­
route
extrapolation
uncertainty
factor
is
applied.
In
such
cases,
an
inhalation
study
would
be
required
to
confirm
these
findings.
A
summary
of
the
results
of
the
occupational
handler
assessment
is
provided
in
Table
6.
17
Table
6:
Short
and
Intermediate
Term
Azadioxabicyclooctane
Exposures
and
MOEs
Associated
with
Occupational
Handlers
a:
The
maximum
application
rate
of
0.5%
product
(
0.25%
a.
i).
by
weight
of
material
treated
generates
an
MOE
of
concern,
whereas
using
materials
treated
at
the
minimum
application
rates
specified
in
the
table,
an
MOE
that
is
not
of
concern
is
generated.
All
of
these
uses
in
Table
6.2
were
assessed
at
this
rate,
except
for
metalworking
fluids.
This
treatment
was
label
specified
to
be
0.3
%
product
(
0.15%
a.
i.)
by
weight
of
the
fluid
treated.

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

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

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

and
0.830
mg/
lb
a.
i.,
respectively.

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

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

Daily
Dose
(
mg
a.
i./
kg
per
day)
MOEr
Substrate
Treated/
Handled
through
Exposure
Scenario
Method
of
Application
Application
rate
(%
a.
i.
by
weight
of
material
being
treated)
Quantity
Handled/
Treated
per
day
(
unit
as
indicated)
Dermal
Dose
Inhalation
Dose
Dermal
(
target
ST/
IT
MOE
=
300)
Inhalation
(
target
MOE
=
300)

Liquid
Pour
(
preservation)
0.25
(
max)
19,100
lbs
(
2,000
gallons)
0.0921
0.00236
1,100
4,500
Liquid
Pump
(
preservation)
0.25
(
max)
191,000
lbs
(
20,000
gallons)
0.0429
0.00275
2,300
3,800
Airless
spraying
(
end
user)
0.25
(
max)
500
lbs
(
50
gallons)
0.25
0.0148
400
720
Airless
spraying
(
end
user)
0.05
(
min)
500
lbs
(
50
gallons)
0.05
0.00296
2,000
3,600
Latex
Paint
(
Latex
Emulsions)
s
Brush
Painting
(
end
user)
0.25
(
max)
50
lbs
(
5
gallons)
0.0429
0.0005
2,300
21,000
Liquid
Pour
0.15
(
max)
2,865
lbs
(
300
gallons)
0.0113
0.000524
8,900
20,000
Metalworking
cutting
fluids
(
preservation)
Liquid
Pump
0.15
(
max)
2,865
lbs(
300
gallons)
0.0192
0.000214
5,200
50,000
Paper
Coating
(
preservation)
Liquid
Pump
0.25
(
max)
9,550
lbs
(
1000
gallons)
0.0015
0.000090
65,000
120,000
Drilling
Muds
(
end
user)
Liquid
Pour
0.25
(
max)
46.7
lbs(
5.6
gal
(
ST))
0.0002
0.000006
440,000
1.8
x
106
Flooding
Fluids
(
end­
user)
23.3
lbs(
2.8
gal
(
IT))
0.0001
0.000003
890,000
3.7
x
106
18
p:
For
the
quantity
handled,
it
is
explained
in
the
MOE
discussion
following,
which
addresses
each
scenario
individually
q:
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Daily
Dose
(
mg
a.
i./
kg
per
day)
=
Unit
Exposure
(
mg/
lb
a.
i.)
x
rate
x
amount
handled
x
(
1/
body
weight
(
kg))

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

t:
There
is
a
chemical
metering
application
(
i.
e.
liquid
pump)
for
drilling
muds
and
flooding
fluid
uses.
However,
this
was
not
assessed
because
appropriate
unit
exposure
values
are
not
available.
This
is
further
discussed
in
the
End
User
discussion
later
in
the
document.
19
d.
Occupational
Post­
application
Occupational
painter
post­
application
exposures
result
when
bystanders
contact
areas
in
which
the
antimicrobial
end­
use
product
has
been
recently
applied.
For
azadioxabicyclooctane,
exposures
are
expected
to
be
minimal
except
for
the
metal
working
fluid
scenario.

Metalworking
Fluids:

There
is
a
potential
for
dermal
and
inhalation
exposure
when
a
worker
handles
treated
metalworking
fluids.
This
route
of
exposure
occurs
after
the
chemical
has
been
incorporated
into
the
metal
working
fluid
and
a
machinist
is
using/
handling
this
treated
end­
product.
The
MOEs
are
in
Table
7
for
this
exposure
scenario.
A
screening­
level
long­
term
dermal
exposure
estimate
was
derived
using
the
2­
hand
immersion
model
from
ChemSTEER.
The
model
is
available
at
www.
epa.
gov/
opptintr/
exposure/
docs/
chemsteer.
htm
Table
7.
Post
Application
Risks
to
Machinists
from
Metal
Working
Fluid
Use
Daily
Dose
Long
Term
MOE
Substrate
Treated/
Handled
through
Exposure
Scenario
Method
of
Application
Application
Rate
(%
a.
i.
by
weight
of
material
being
treated)
Dermal
Dose
Inhalation
Dose
Dermal
Inhalation
Liquid
Pour
Liquid
Pump
0.15
0.1854
0.00107
540
9900
Metalworking
cutting
fluids
Liquid
Pour
Liquid
Pump
0.05
0.0618
0.000357
1,600
30,000
At
the
maximum
application
rate
(
0.3%
product
by
weight
of
material
to
be
treated,
0.15%
a.
i.)
permitted
for
metalworking
fluids
(
MWF),
there
is
concern
with
the
dermal
exposure
to
the
worker.
The
target
MOE
for
long­
term
exposure
is
1,000,
and
at
the
maximum
rate,
the
MOE
is
540,
which
is
a
concern.
However,
when
the
worker
comes
into
contact
with
fluid
that
has
been
treated
at
the
minimum
application
rate
(
0.1%
product
by
weight
of
material
to
be
treated,
0.05%
a.
i.),
the
MOE
is
1,600
which
is
not
of
concern
since
it
is
greater
than
1,000.

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
azadioxabicyclooctane
use
sites
and
any
associated
uncertainties.

1.
Environmental
Fate
and
Transport
The
environmental
fate
assessment
for
azadioxabicyclooctane
is
based
on
U.
S.
EPA=
s
Estimation
Programs
Interface
(
EPI)
Suite.
EPI
Suite
provides
estimations
of
physical/
chemical
20
properties
and
environmental
fate
properties.
Azadioxabicyclooctane
is
a
mixture
of
three
acetals
(
components
a,
b
and
c).
EPI
Suite
lacks
estimation
of
the
third
of
the
three
isomers
(
component
C).

Under
abiotic
conditions,
the
mixture
of
these
acetals
is
hydrolytically
unstable
with
halflives
of
0.347
days
at
pH
5,
1.74
days
at
pH
7
and
approximately
15
days
at
pH
9.
It
is,
therefore,
not
likely
to
be
persistent
in
water.

Components
A
and
B
of
the
mixture
are
likely
to
volatilize
into
the
atmosphere
as
their
vapor
pressures
vary
between
0.0004
to
0.003
mm
Hg.
Component
C
is
likely
to
have
less
volatility
as
the
side
chain
of
CH2O
groups
are
added
into
the
structure.
Estimated
half
lives
in
the
atmosphere
for
components
A
and
B
are
1.2
and
1.4
hours.
Hence,
these
two
chemicals
are
not
likely
to
persist
in
the
atmosphere.

Estimated
log
Kows
of
components
A
and
B
respectively
are
­
2.23
and
­
1.55
(
very
highly
miscible
in
water
and
show
no
tendency
for
dissolving
organic
solvents);
therefore,
the
mixture
is
not
likely
to
bioaccumulate
in
aquatic
organisms.

MITI
linear
biodegradability
(
modified
linear
biodegradation
method)
for
components
A
and
B
indicates
a
fast
biodegradation
is
highly
probable
in
soils
and
water.
These
compounds
do
not
likely
pose
a
concern
for
surface
and
ground
water
contamination.

2.
Ecological
Risk
Azadioxabicyclooctane
demonstrates
low
toxicity
to
birds
and
mammals
and
slight
toxicity
to
freshwater
aquatic
organisms.
All
submitted
ecological
toxicity
studies
were
conducted
with
the
formulated
product
Nuosept7
95.
Although
conducted
using
a
formulated
product
and
not
the
TGAI,
the
submitted
studies
for
avian
acute,
avian
subacute,
freshwater
invertebrates
and
estuarine/
marine
organisms
are
considered
adequate
to
support
the
registered
uses
of
azadioxabicyclooctane,
as
Nuosept7
95
is
the
only
end­
use
product.
A
summary
of
submitted
data
is
provided
below.

The
indoor
uses
of
azadioxabicyclooctane
are
not
likely
to
pose
risk
to
fish,
wildlife
or
plants
due
to
the
low
likelihood
of
exposure
and
the
low
toxicity
of
the
compound.
Most
uses
of
azadioxabicyclooctane
are
indoor
uses,
with
little
chance
of
exposure
to
the
environment.
The
oil
production
uses
do
occur
outdoors;
however,
the
Agency
does
not
have
an
available
model
for
estimating
exposure
from
those
uses.
The
risk
from
offshore
oil
drilling
uses
of
azadioxabicyclooctane
was
previously
addressed
(
Agency
review
July
14,
1983),
and
the
application
of
500­
2000
ppm
drilling
fluid
treatment
or
100­
1000
ppm
flooding
fluid
treatment
was
considered
Aunlikely
to
adversely
affect
aquatic
organisms
due
to
the
low
toxicity
and
large
dilution
factor.@
Discharge
of
waste
streams
occurring
from
terrestrial
oil
recovery
operations
would
be
regulated
at
the
local
level
in
order
to
prevent
undue
environmental
exposure.
21
Table
8.
Acute
Oral
Toxicity
of
Nuosept7
95
to
Birds
Species
%
Active
Ingredient
(
ai)
Endpoint
(
mg
/
kg
product)
Toxicity
Category
Reference
Mallard
duck
(
Anas
platyrhynchos)
107001
24.5%
107002
17.7%
107003
7.8%
LD50
>
2,510
NOEL
=
2510
(
mortality)
Practically
non­
toxic
Beavers,
1983
(
ACC
#
250533)

Table
9.
Subacute
Dietary
Toxicity
of
Nuosept7
95
to
Birds
Species
%
Active
Ingredient
(
ai)
Endpoint
(
ppm)
Toxicity
Category
Reference
Bobwhite
quail
(
Colinus
virginianus)
50%
LC50
>
5,200
a.
i.
(>
10,400
product)
NOEC
1541
ppm
a.
i.
(
3082
ppm
product)
Practically
non­
toxic
Hakin
et
al.,
1990
(
MRID
416848­
01)

Bobwhite
quail
(
Colinus
virginianus)
not
reported
LC50
>
10,000
ppm
product
NOEC
10,000
ppm
Practically
non­
toxic
Truslow
Farms,
1974.
(
ACC#
24878)

Mallard
duck
(
Anas
platyrhynchos)
not
reported
LC50
>
10,000
ppm
product
NOEC
10,000
ppm
Practically
non­
toxic
Truslow
Farms,
1974.
(
ACC#
24878)

NOAEC=
No­
observable
adverse
effect
concentration
22
Table
10.
Acute
Toxicity
of
Nuosept7
95
to
Fish
Species
%
Active
Ingredient
(
a.
i.)
Endpoints
(
ppm
product)
Toxicity
Category
Reference
Rainbow
trout
(
Oncorhynchus
mykiss)
not
reported
LC50
=
240
NOEC
=
87
practically
non­
toxic
Bentley
and
Sleight,
1974
(
ACC
#
247878;
MRID
930500­
15)

Bluegill
(
Lepomis
macrochirus)
not
reported
LC50
=
163
NOEC
=
87
practically
non­
toxic
Bently
and
Bevier,
1974
(
ACC#
247878;
MRID
930500­
15)

Sheepshead
minnow
(
Cyprinodon
variegatus)
PC
code
%
107001
24.5%
107002
17.7%
107003
7.8%
LC50
=
440
ppm
NOEC
=
250
ppm
practically
non­
toxic
Ward,
1983.
(
ACC#
250533)

Table
11.
Acute
Toxicity
of
Nuosept7
95
to
Invertebrates
Species
%
Active
Ingredient
(
ai)
Endpoints
(
ppm
product)
Toxicity
Category
Reference
Eastern
oyster
(
Crassostrea
virginica)
PC
Code
%
107001
24.5%
107002
17.7%
107003
7.8%
EC50
=
42
NOEC
=
25
slightly
toxic
Ward,
1983.
(
ACC#
250533)

Mysid
(
Americamysis
bahia)
107001
24.5%
107002
17.7%
107003
7.8%
LC50
=
88
ppm
NOEC
<
50
ppm\
slightly
toxic
Ward,
1983.
ACC#
250533
Water
flea
(
Daphnia
magna)
107001
24.5%
107002
17.7%
107003
7.8%
EC50
=
77
NOEC
=
7.7
slightly
toxic
Suprenant,
1983
(
ACC#
250533/
MRID
#
930500­
16)
23
3.
Listed
Species
Consideration
a.
The
Endangered
Species
Act
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
II
B,
pg.
81).
Chemicals
in
these
categories
therefore
do
not
undergo
a
full
screening­
level
risk
assessment,
and
are
considered
to
fall
under
a
"
no
effect"
determination.
Due
to
the
low
likelihood
of
exposure
and
low
toxicity
of
azadioxabicyclooctane,
the
indoor
uses
of
the
compound
are
not
likely
to
adversely
affect
listed
species.
Likewise,
offshore
oil
production
use
of
azadioxabicyclooctane
is
considered
unlikely
to
adversely
affect
listed
species
due
to
the
low
toxicity
of
the
compound
and
the
large
dilution
factor
in
offshore
operations.
Therefore,
the
Agency
expects
no
effects
to
listed
species
or
critical
habitat
and
therefore
makes
a
"
No
Effect"
determination
for
this
chemical.

b.
General
Risk
Mitigation
Azadioxabicyclooctane
end­
use
products
(
EPs)
may
also
contain
other
registered
pesticides.
Although
the
Agency
is
not
proposing
any
mitigation
measures
for
products
24
containing
azadioxabicyclooctane
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
conflicting
listed
species
risk
mitigation
measures,
the
more
stringent
measure(
s)
should
be
adopted.
25
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
azadioxabicyclooctane
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
azadioxabicyclooctane.

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
azadioxabicyclooctane.
Based
on
a
review
of
these
data
and
on
public
comments
on
the
Agency's
assessments
for
the
active
ingredient
azadioxabicyclooctane,
the
Agency
has
sufficient
information
on
the
human
health
and
ecological
effects
of
azadioxabicyclooctane
to
make
decisions
as
part
of
the
tolerance
reassessment
process
under
FFDCA
and
reregistration
process
under
FIFRA,
as
amended
by
FQPA.
The
Agency
has
determined
that
all
azadioxabicyclooctane
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.
Label
changes
are
described
in
Section
V.
Appendix
A
summarizes
the
uses
of
azadioxabicyclooctane
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
azadioxabicyclooctane,
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
azadioxabicyclooctane,
the
Agency
has
determined
that
azadioxabicyclooctane
products,
unless
labeled
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
azadioxabicyclooctane.
If
all
changes
outlined
in
this
document
are
incorporated
into
the
product
labels,
then
all
current
risks
for
azadioxabicyclooctane
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
azadioxabicyclooctane.
During
the
public
comment
period
on
the
risk
assessments,
which
closed
on
September
19,
2005,
the
Agency
received
comments
from
the
registrant,
International
Speciality
Products.
These
comments
in
their
entirety
are
available
in
the
public
docket,
http://
docket.
epa.
gov/
edkpub/
index.
jsp,
(
OPP­
2005­
0186).
These
comment
have
been
considered
in
the
writing
of
this
RED.
26
The
registrant
also
submitted
comments
to
the
Agency
during
Phase
1,
the
error
only
comment
period.
The
Agency's
responses
to
these
comments
are
incorporated
into
the
revised
chapters
and
are
available
in
the
public
docket.

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
azadioxabicyclooctane.
An
aggregate
assessment
was
conducted
for
exposures
through
food,
drinking
water
and
residential
use.
The
Agency
has
determined
that
the
human
health
risks
from
these
combined
exposures
are
within
acceptable
levels
with
the
mitigation
contained
in
this
document.
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,
water
and
residential
use.

b.
Determination
of
Safety
to
U.
S.
Population
As
part
of
the
FQPA
tolerance
reassessment
process,
EPA
assessed
the
risks
associated
with
azadioxabicyclooctane.
The
Agency
has
determined
that
there
is
a
reasonable
certainty
no
harm
will
result
to
the
general
population
or
any
subgroup
from
the
use
of
azadioxabicyclooctane
with
amendments
and
changes
as
specified
in
this
document.
In
reaching
this
conclusion,
the
Agency
has
considered
all
available
information
on
the
toxicity,
use
practices
and
exposure
scenarios,
and
the
environmental
behavior
of
azadioxabicyclooctane.
Both
the
acute
dietary
(
food
alone)
and
chronic
dietary
risks
from
azadioxabicyclooctane
are
not
of
concern.
Azadioxabicyclooctane
is
not
likely
to
contaminate
surface
and
ground
waters
based
on
its
use
patterns.
Thus,
a
drinking
water
assessment
was
not
conducted.

Because
the
Agency
has
concerns
for
residential
handler
risks
for
the
paint
scenario
short­
and
intermediate­
term
aggregate
risk
assessments
were
not
conducted
for
azadioxabicyclooctane
since
this
use
alone
exceeds
the
Agency's
level
of
concern.

c.
Determination
of
Safety
to
Infants
and
Children
EPA
has
determined
that
the
established
tolerances
for
azadioxabicyclooctane,
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
azadioxabicyclooctane
residues
in
this
population
subgroup.

A
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
27
from
azadioxabicyclooctane
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
retained
(
i.
e.,
remains
10X)
for
azadioxabicyclooctane
based
on
the
very
limited
developmental
and
reproductive
toxicity
databases.
d.
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
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
endocrine
effects
as
the
Administrator
may
designate."
Following
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
EPA
include
evaluations
of
potential
effects
in
wildlife.
For
pesticides,
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).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
EDSP
have
been
developed,
azadioxabicyclooctane
may
be
subject
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

e.
Cumulative
Risks
Risks
summarized
in
this
document
are
those
that
result
only
from
the
use
of
azadioxabicyclooctane.
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
azadioxabicyclooctane.
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/.
28
D.
Regulatory
Rationale
The
Agency
has
determined
that
azadioxabicyclooctane
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
azadioxabicyclooctane.
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
For
all
supported
uses,
the
acute
and
chronic
dietary
exposure
estimates
are
below
the
Agency's
level
of
concern.
Therefore,
no
risk
mitigation
measures
are
required
to
address
exposure
to
azadioxabicyclooctane
residues
in
food.

b.
Drinking
Water
Risk
Mitigation
Azadioxabicyclooctane
is
not
likely
to
contaminate
surface
and
ground
waters
based
on
its
use
patterns.
Thus,
a
drinking
water
assessment
was
not
conducted.
Therefore,
no
risk
mitigation
measures
are
required
to
address
azadioxabicyclooctane
exposure
from
drinking
water.

c.
Residential
Risk
Mitigation
Residential
risks
for
handlers
were
calculated
for
short­
and
intermediate­
term
dermal
and
inhalation
exposures.
Risks
of
concern
were
identified
for
the
application
of
paints
using
an
airless
sprayer
at
the
maximum
application
rate
of
0.5%
product
by
weight
of
material
treated.
All
other
exposure
and
risk
estimates
for
residential
handler
scenarios
are
below
the
Agency's
level
of
concern.

To
reduce
residential
exposure,
the
Agency
has
determined
that
the
following
mitigation
and
label
change
for
specific
scenarios
is
appropriate
and
required
for
reregistration
eligibility:

 
Reduce
the
maximum
application
rate
for
paint
uses
to
0.4%
product
by
weight
of
material
treated.

d.
Occupational
Risk
Mitigation
i.
Handler
Exposure
Occupational
risks
from
handler
and
applicator
exposures
were
calculated
for
short­
term
and
intermediate­
term
dermal
and
inhalation
exposures.
All
exposure
and
risk
estimates
for
29
occupational
handler
scenarios
are
below
the
Agency's
level
of
concern.
Therefore,
no
risk
mitigation
measures
are
required
for
these
handler
scenarios.

ii.
Post­
Application
Risk
Mitigation
Occupational
risks
from
post­
application
exposure
were
calculated
for
long­
term
dermal
and
inhalation
exposures
to
machinists
resulting
from
metal
working
fluid
use.
Risks
of
concern
were
identified
for
this
use
pattern
at
the
maximum
application
rate
of
0.3%
product
by
weight
of
material
treated.

To
reduce
post­
application
exposure,
the
Agency
has
determined
that
the
following
mitigation
and
label
change
for
specific
scenarios
is
appropriate
and
required
for
reregistration
eligibility:

 
Reduce
the
maximum
application
rate
for
paint
uses
to
0.2%
product
by
weight
of
material
treated
2.
Environmental
Risk
Management
As
the
uses
of
azadioxabicyclooctane
considered
in
this
RED
make
it
unlikely
that
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms
would
occur,
no
risk
mitigation
measures
are
required
to
address
environmental
exposure
to
azadioxabicyclooctane.

3.
Other
Labeling
Requirements
In
order
to
be
eligible
for
reregistration,
various
use
and
safety
information
will
be
included
in
the
labeling
of
all
end­
use
products
containing
azadioxabicyclooctane.
For
the
specific
labeling
statements
and
a
list
of
outstanding
data,
refer
to
Section
V
of
this
RED
document.

4.
Threatened
and
Endangered
Species
Considerations
a.
The
Endangered
Species
Program
The
Agency
has
developed
the
Endangered
Species
Protection
Program
to
identify
pesticides
whose
use
may
cause
adverse
impacts
on
endangered
and
threatened
species,
and
to
implement
mitigation
measures
that
address
these
impacts.
The
Endangered
Species
Act
requires
federal
agencies
to
ensure
that
their
actions
are
not
likely
to
jeopardize
listed
species
or
adversely
modify
designated
critical
habitat.
To
analyze
the
potential
of
registered
pesticide
uses
to
affect
any
particular
species,
EPA
puts
basic
toxicity
and
exposure
data
developed
for
risk
assessments
into
context
for
individual
listed
species
and
their
locations
by
evaluating
important
ecological
parameters,
pesticide
use
information,
the
geographic
relationship
between
specific
pesticide
uses
and
species
locations,
and
biological
requirements
and
behavioral
aspects
of
the
particular
species.
A
determination
that
there
is
a
likelihood
of
potential
impact
to
a
listed
species
may
result
in
limitations
on
use
of
the
pesticide,
other
measures
to
mitigate
any
potential
impact,
or
consultations
with
the
Fish
and
Wildlife
Service
and/
or
the
National
Marine
Fisheries
Service
as
necessary.
30
Due
to
the
low
likelihood
of
exposure
and
low
toxicity
of
azadioxabicyclooctane,
the
indoor
uses
of
the
compound
are
not
likely
to
adversely
affect
listed
species.
Likewise,
offshore
oil
production
use
of
azadioxabicyclooctane
is
considered
unlikely
to
adversely
affect
listed
species
due
to
the
low
toxicity
of
the
compound
and
the
large
dilution
factor
in
offshore
operations.
Therefore,
the
Agency
expects
no
effects
to
listed
species
or
critical
habitat
and
therefore
makes
a
"
No
Effect"
determination
for
this
chemical.

b.
General
Risk
Mitigation
Azadioxabicyclooctane
end
use
products
(
EPs)
may
also
contain
other
registered
pesticides.
Although
the
Agency
is
not
proposing
any
mitigation
measures
for
products
containing
azadioxabicyclooctane
specific
to
federally
listed
threatened
and
endangered
species,
the
Agency
needs
to
address
potential
risks
from
other
end­
use
products.
Therefore,
the
Agency
requires
that
users
adopt
all
threatened
and
endangered
species
risk
mitigation
measures
for
all
active
ingredients
in
the
product.
If
a
product
contains
multiple
active
ingredients
with
conflicting
threatened
and
endangered
species
risk
mitigation
measures,
the
more
stringent
measure(
s)
should
be
adopted.
31
V.
What
Registrants
Need
to
Do
The
Agency
has
determined
that
azadioxabicyclooctane
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.
To
implement
the
risk
mitigation
measures,
the
registrants
must
amend
their
product
labeling
to
incorporate
the
label
statements
set
forth
in
the
Label
Changes
Summary
Table
in
Section
B
below
(
Table
13).
The
additional
data
requirements
that
the
Agency
intends
to
obtain
will
include,
among
other
things,
submission
of
the
following:

For
azadioxabicyclooctane
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
Tom
Luminello
at
(
703)
308­
8075
with
questions
regarding
generic
reregistration.

By
US
mail:
By
express
or
courier
service:
Document
Processing
Desk
(
DCI/
AD)
Document
Processing
Desk
(
DCI/
AD)
Tom
Luminello
Tom
Luminello
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
32
For
end
use
products
containing
the
active
ingredient
azadioxabicyclooctane,
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
(
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
(
CSF)
(
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
13
of
this
document;

4.
A
completed
form
certifying
compliance
with
data
compensation
requirements
(
EPA
Form
8570­
34);

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
6341
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
(
PM­
31)
Document
Processing
Desk
(
PM­
31)
Marshall
Swindell
Marshall
Swindell
US
EPA
(
7510C)
Office
of
Pesticide
Programs
(
7510C)
1200
Pennsylvania
Ave.,
NW
Room
266A,
Crystal
Mall
2
Washington,
DC
20460
1801
South
Bell
Street
Arlington,
VA
22202
33
A.
Manufacturing
Use
Products
1.
Additional
Generic
Data
Requirements
The
generic
database
supporting
the
reregistration
of
azadioxabicyclooctane
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
in
will
be
issued
at
a
later
date.
The
90­
day
inhalation
study
is
being
required
to
confirm
the
Agency's
conclusions
on
residential
risks.

EPA
requires
that
the
registrant
submit
carcinogenicity
data
for
azadioxabicyclooctane
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
azadioxabicyclooctane.
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.
The
Agency
also
conducts
a
literature
search
and
can
also
conduct
a
Structural
Activity
Relationship
analysis
(
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
and
a
subchronic
toxicity
study
in
a
non­
rodent
species
are
being
held
in
reserve
for
azadioxabicyclooctane.

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.
34
Table
12.
Confirmatory
Data
Requirements
for
Reregistration
Guideline
Study
Name
New
OPPTS
Guideline
No.
Old
Guideline
No.

Skin
Sensitization
870.2600
81­
6
90­
Day
Inhalation
Toxicity
Study­
Rat
870.3465
82­
4
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
90­
Day
Oral
Toxicity
in
Non­
Rodents
870.3150
82­
1
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.
The
Technical
and
MP
labeling
should
bear
the
labeling
contained
in
Table
13,
Label
Changes
Summary
Table.

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,
outlining
specific
data
requirements,
will
follow
this
RED
at
a
later
date.

2.
Labeling
for
End­
Use
Products
Labeling
changes
are
necessary
to
implement
measures
outlined
in
Section
IV
above.
Specific
language
to
incorporate
these
changes
is
specified
in
Table
13.

Registrants
may
generally
distribute
and
sell
products
bearing
old
labels/
labeling
for
26
months
from
the
date
of
the
issuance
of
this
Reregistration
Eligibility
Decision
document.
35
Persons
other
than
the
registrant
may
generally
distribute
or
sell
such
products
for
52
months
from
the
approval
of
labels
reflecting
the
mitigation
described
in
this
RED.
However,
existing
stocks
time
frames
will
be
established
case­
by­
case,
depending
on
the
number
of
products
involved,
the
number
of
label
changes,
and
other
factors.
Refer
to
"
Existing
Stocks
of
Pesticide
Products;
Statement
of
Policy,"
Federal
Register,
Volume
56,
No.
123,
June
26,
1991.

a.
Label
Changes
Summary
Table
In
order
to
be
eligible
for
reregistration,
amend
all
product
labels
to
incorporate
the
risk
mitigation
measures
outlined
in
Section
IV.
The
following
table
describes
how
language
on
the
labels
should
be
amended.
36
Table
13.
Labeling
Changes
Summary
Table
Summary
of
Labeling
Changes
for
Azadioxabicyclooctane
Description
Amended
Labeling
Language
Placement
on
Label
Reduce
rate
for
paint
applications
Maximum
rate
for
paint
applications
is
0.4%
product
by
weight
of
material
treated
Directions
for
Use
Reduce
rate
for
metal
working
fluids
applications
Maximum
rate
for
metal
working
fluids
applications
is
0.2%
product
by
weight
of
material
treated
Directions
for
Use
37
38
VI.
APPENDICES
39
Appendix
A.
Table
of
Use
Patterns
for
Azadioxabicyclooctane
Use
Site
Formulation
Method
of
Application
Application
Rate
(
Range)
a
Use
Limitations
Industrial
and
Manufacturing
Facilities
Adhesives
(
natural­
based)
1529­
28
Open
pour
0.2
 
0.5
%
by
weight
of
formulation
Add
to
water
phase
or
post
addition.

Adhesives
(
synthetic)
1529­
28
Open
pour
0.1
 
0.5
%
by
weight
of
formulation
Add
to
water
phase
or
post
addition.

Caulks
1529­
28
Open
pour
0.1
 
0.5
%
by
weight
of
formulation
Add
to
water
phase
during
manufacture.

Drilling
Muds
1529­
28
Open
pour
0.05
 
0.2
%
by
weight
of
formulation
Add
to
water
phase
or
post
addition.

Flooding
Fluids
1529­
28
Open
pour
0.01
 
0.1
%
by
weight
of
formulation
Post
addition.

Latex
Emulsion
1529­
28
Open
pour
0.05
 
0.3
%
by
weight
of
formulation
Post
addition.

Wax
Emulsion
1529­
28
Open
pour
0.05
 
0.3
%
by
weight
of
formulation
Post
addition.

Latex
Paint
1529­
28
Open
pour
0.1
 
0.5
%
by
weight
of
formulation
Add
at
any
point
during
manufacture.

a
The
optimum
amount
of
Nuosept
95
Preservative
required
for
adequate
preservation
is
best
determined
by
conducting
a
series
of
test
loadings
and
making
adjustments.
The
maximum
level
permitted
for
metal­
working
fluids
is
0.3%.
The
maximum
level
permitted
for
all
other
applications
is
0.5%
40
Use
Site
Formulation
Method
of
Application
Application
Rate
(
Range)
a
Use
Limitations
Inks
1529­
28
Open
pour
0.1
 
0.5
%
by
weight
of
formulation
Post
addition.

Paper
Coatings
1529­
28
Open
pour
0.1
 
0.5
%
by
weight
of
formulation
Must
be
limited
to
contact
with
dry
food.

Add
to
water
phase
or
post
addition.

Pigment
Dispersion
1529­
28
Open
pour
0.1
 
0.3
%
by
weight
of
formulation
Add
at
any
point
during
manufacture.

Pigment
Slurry
1529­
28
Open
pour
0.05
 
0.1
%
by
weight
of
formulation
Add
to
water
phase
or
post
addition.

Sealants
1529­
28
Open
pour
0.1
 
0.5
%
by
weight
of
formulation
Add
to
water
phase
during
manufacture.

Metalworking
Fluids
1529­
28
Open
pour
0.1
 
0.3
%
by
weight
of
formulation
Add
to
water
phase
during
manufacture
and
service.

Textile
Fiber
Finish
1529­
28
Open
pour
0.05
 
0.1
%
by
weight
of
formulation
For
use
on
fibers
that
are
not
in
direct
contact
with
skin.

Add
at
any
point
during
manufacture.

a
The
optimum
amount
of
Nuosept
95
Preservative
required
for
adequate
preservation
is
best
determined
by
conducting
a
series
of
test
loadings
and
making
adjustments.
The
maximum
level
permitted
for
metal­
working
fluids
is
0.3%.
The
maximum
level
permitted
for
all
other
applications
is
0.5%.
41
APPENDIX
B:
Azadioxabicyclooctane
(
Case
3023)

Appendix
B
lists
the
generic
(
not
product
specific)
data
requirements
which
support
the
re­
registration
of
azadioxabicyclooctane.

These
requirements
apply
to
azadioxabicyclooctane
in
all
products,
including
data
requirements
for
which
a
technical
grade
active
ingredient
is
the
test
substance.
The
data
table
is
organized
in
the
following
formats:

1.
Data
Requirement
(
Columns
1
and
2).
The
data
requirements
are
listed
by
Guideline
Number.
The
first
column
lists
the
new
Part
158
Guideline
numbers,
and
the
second
column
lists
the
old
Part
158
Guideline
numbers.
Each
Guideline
Number
has
an
associated
test
protocol
set
forth
in
the
Pesticide
Assessment
Guidance,
which
are
available
on
the
EPA
website.

2.
Guideline
Description
(
Column
3).
Identifies
the
guideline
type.

3.
Use
Pattern
(
Column
4).
This
column
indicates
the
standard
Antimicrobial
Division
use
patterns
categories
for
which
the
generic
(
not
product
specific)
data
requirements
apply.
The
number
designations
are
used
in
Appendix
B.

(
1)
Agricultural
premises
and
equipment
(
2)
Food
handling/
storage
establishments
premises
and
equipment
(
3)
Commercial,
institutional
and
industrial
premises
and
equipment
(
4)
Residential
and
public
access
premises
(
5)
Medical
premises
and
equipment
(
6)
Human
water
systems
(
7)
Materials
preservatives
(
8)
Industrial
processes
and
water
systems
(
9)
Antifouling
coatings
(
10)
Wood
preservatives
(
11)
Swimming
pools
(
12)
Aquatic
areas
3.
Bibliographic
Citation
(
Column
5).
If
the
Agency
has
data
in
its
files
to
support
a
specific
generic
Guideline
requirement,
this
column
will
identity
each
study
by
a
"
Master
Record
Identification
(
MRID)
number.
The
listed
studies
are
considered
"
valid"
and
acceptable
for
satisfying
the
Guideline
requirement.
Refer
to
the
Bibliography
appendix
for
a
complete
citation
of
each
study.
42
DATA
REQUIREMENT
CITATION(
S)

New
Guideline
Number
Old
Guideline
Number
Study
Title
Use
Pattern
MRID
Number
PRODUCT
CHEMISTRY
830.1550
61­
1
Product
Identity
and
Composition
All
42734301,
41671601,
41671602,41671603
830.1600
830.1620
830.1650
61­
2a
Starting
Materials
and
Manufacturing
Process
All
42734301,
41671601,
41671602,41671603
830.1670
61­
2b
Formation
of
Impurities
All
42734301,
41671601,
41671602,41671603
830.1700
62­
1
Preliminary
Analysis
All
42734301,
41671601,
41671602,41671603
830.1750
62­
2
Certification
of
Limits
All
42740801,
41671601,
41671602,41671603
830.1800
62­
3
Analytical
Method
All
42740801,
41671601,
41671602,41671603
830.6302
63­
2
Color
All
42734301,
41671601,
41671602,41671603
830.6303
63­
3
Physical
State
All
42734301,
41671601,
41671602,41671603
830.6304
63­
4
Odor
All
42734301,
41671601,
41671602,41671603
830.7050
None
UV/
Visible
Absorption
All
42734301,
41671601,
41671602,41671603
830.7200
63­
5
Melting
Point
All
42734301,
41671601,
41671602,41671603
830.7220
63­
6
Boiling
Point
All
42734301,
41671601,
41671602,41671603
830.7300
63­
7
Density
All
42734301,
41671601,
41671602,41671603
830.7840
830.7860
63­
8
Solubility
All
42734301,
41671601,
41671602,41671603
830.7950
63­
9
Vapor
Pressure
All
42734301,
41671601,
41671602,41671603
830.7370
63­
10
Dissociation
Constant
in
Water
All
42734301,
41671601,
41671602,41671603
43
DATA
REQUIREMENT
CITATION(
S)

New
Guideline
Number
Old
Guideline
Number
Study
Title
Use
Pattern
MRID
Number
830.7550
830.7560
830.7570
63­
11
Partition
Coefficient
(
Octanol/
Water)
All
42734301,
41671601,
41671602,41671603
830.7000
63­
12
pH
All
42734301,
41671601,
41671602,41671603
830.6313
63­
13
Stability
All
42734301,
41671601,
41671602,41671603
830.6314
63­
14
Oxidizing/
Reducing
Action
All
42734301,
41671601,
41671602,41671603
830.6315
63­
15
Flammability
All
42734301,
41671601,
41671602,41671603
830.6316
63­
16
Explodability
All
42734301,
41671601,
41671602,41671603
830.6317
63­
17
Storage
Stability
All
42734301,
41671601,
41671602,41671603
830.7100
63­
18
Viscosity
All
42734301,
41671601,
41671602,41671603
830.6319
63­
19
Miscibility
All
42734301,
41671601,
41671602,41671603
830.6320
63­
20
Corrosion
Characteristics
All
42734301,
41671601,
41671602,41671603
ECOLOGICAL
EFFECTS
850.2100
71­
1
Avian
Acute
Oral
Toxicity
Test
(
Mallard
Duck)
All
129008
850.2200
71­
2
Avian
Dietary
Toxicity
(
Bobwhite
Quail)
4164801,112791
850.2200
71­
2b
Avian
Dietary
Toxicity
(
Mallard
Duck)
112792
850.1075
72­
1a
Fish
Acute
Toxicity
 
Freshwater
(
Blue
Gill)
All
109246
850.1075
72­
1c
Fish
Acute
Toxicity
 
Freshwater
(
Rainbow
Trout)
109246
850.1010
72­
2
Acute
Aquatic
Invertebrate
Toxicity
(
Daphnid)
129009
850.1025
72­
3B
Estuarine/
Marine
Toxicity
­
Mollusk
129012
TOXICOLOGY
44
DATA
REQUIREMENT
CITATION(
S)

New
Guideline
Number
Old
Guideline
Number
Study
Title
Use
Pattern
MRID
Number
870.1100
81­
1
Acute
Oral
­
Rat
All
41641601
870.1200
81­
2
Acute
Dermal
­
Rabbit
All
41671801
870.1300
81­
3
Acute
Inhalation
­
Rat
All
42650901
870.2400
81­
4
Primary
Eye
Irritation
­
Rabbit
All
41641602
870.2500
81­
5
Primary
Dermal
Irritation
­
Rabbit
All
41641603
870.2600
81­
6
Dermal
Sensitization
All
41641604
870.3100
82­
1a
90­
Day
Feeding­
Rodent
All
41641606
870.3200
82­
2
21/
28­
Day
Dermal
Toxicity
­
Rat
All
41641605
870.3250
82­
3
90­
day
Dermal
Toxicity
­
Rodent
All
870.3465
82­
4
28/
90­
Day
Inhalation
­
Rat
All
DG
870.4200
83­
2
Carcinogenicty
DG
870.3700
83­
3
Developmental
Toxicity
­
Rat
All
41537501
870.3700a
83­
3a
Prenatal
Developmental
in
Rodents
All
41699001
870.3700b
83­
3b
Developmental
Toxicity
­
Rabbit
870.5265
84­
2
Bacterial
Reverse
Mutation
Assay
All
870.5395
84­
2
Micronucleus
Assay
All
870.5450
84­
2
Dominant
Lethal
Rat
870.5500
84­
2
Bacterial
DNA
Damager
or
Repair
93050019
870.5550
84­
2
Unscheduled
DNA
Synthesis
Assay
42711001
Reserved
Studies
45
DATA
REQUIREMENT
CITATION(
S)

New
Guideline
Number
Old
Guideline
Number
Study
Title
Use
Pattern
MRID
Number
870.3800
83­
4
2
Generation
Repro
DG,
reserved
study
870.3150
82­
1b
90­
Day
Oral
Subchronic
in
Non­
Rodent
DG,
reserved
study
Other
Genotoxic
Studies
Non­
Guideline
84­
4
In
Vitro
Cell
Transformation
Assay
93050022,
93050024,
93050025
OCCUPATIONAL/
RESIDENTIAL
EXPOSURE
875.2800
133­
1
Descriptions
of
Human
Activity
All
DG
875.1200
875.1600
233/
236
Dermal
Indoor
Exposure
All
DG
875.1400
875.1600
234/
236
Inhalation
Indoor
Exposure
All
DG
ENVIRONMENTAL
FATE
835.2120
161­
1
Hydrolysis
All
43067001
OTHER
DATA
REQUIREMENTS
46
47
Appendix
C.
Technical
Support
Documents
Additional
documentation
in
support
of
this
RED
is
maintained
in
the
OPP
docket,
located
in
room
119,
Crystal
Mall
#
2,
1801
S.
Bell
St.,
Arlington,
VA
22202.
It
is
open
Monday
through
Friday,
excluding
legal
holidays,
from
8:
30
AM
to
4:
00
PM.

The
docket
initially
contained
preliminary
risk
assessments
and
related
documents
as
of
July
20,
2005.
Sixty
days
later
the
first
public
comment
period
closed.
The
EPA
then
considered
comments
and
revised
the
risk
assessments.

All
documents,
in
hard
copy
form,
may
be
viewed
in
the
OPP
docket
room
or
downloaded
or
viewed
via
the
Internet
at
the
following
site:
http://
www.
epa.
gov/
edockets
These
documents
include:

1.
Azadioxabicyclooctane:
AD
Preliminary
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
Document,
July12,
2005
2.
Azadioxabicyclooctane:
Dietary
Exposures
and
Risks
from
Antimicrobial
Indirect
Food
Contact
Uses,
July
7,
2005
3.
Azadioxabicyclooctane:
Occupational
and
Residential
Exposure
Chapter
for
RED,
July,
7,
2005
4.
Azadioxabicyclooctane:
Environmental
Fate
Assessment
of
Nuosept
95
for
RED,
March
1,
2005
5.
Azadioxabicyclooctane:
Product
Chemistry
Science
Chapter
for
RED,
April
6,
2005
6.
Azadioxabicyclooctane:
Report
of
the
Antimicrobials
Division
Toxicology
Endpoint
Selection
Committee,
May
25,
2005
7.
Azadioxabicyclooctane:
Ecological
Hazard
and
Environmental
Risk
Assessment
for
5­
hydroxymethoxymethyl­
1­
aza­
3,
7­
dioxabicyclooctanes
(
Aza),
May
17,
2005
8.
Epidemiology
Assessment
based
on
Incident
Reports,
May
19,
2005
9.
Hazard
Characterization
48
49
Appendix
D:
Generic
Data
Requirements
and
Studies
Used
to
Make
the
Reregistration
Decision
(
Bibliography)

1.
MRID
Studies
MRID#
Citation
109246
Bentley,
R.
(
1974)
Acute
Toxicity
of
Nuosept
95
to
Bluegill
(
Lepomis
macrochirus)
and
Rainbow
Trout
(
Salmo
gairdneri).
(
Unpublished
study
received
Jul
19,
1982
under
92­
35;
prepared
by
Bionomics
EG
&
G,
Inc.,
submitted
by
Tenneco
Chemical,
Inc.,
Piscataway,
N.
J.;
CDL:
247878­
A)

112791
Fink,
R.
(
1974)
Final
Report:
Eight­
day
Dietary
LC50­­
Bobwhite
Quail:
Nuosept
95:
Project
No.
122­
101.
(
Unpublished
study
received
Jul
19,
1982
under
92­
35;
prepared
by
Truslow
Farms,
Inc.,
submitted
by
Tenneco
Chemical,
Inc.,
Piscataway,
NJ;
CDL:
247878­
B)

112792
Fink,
R.
(
1974)
Final
Report:
Eight­
day
Dietary
LC50­­
Mallard
Ducks:
Nuosept
95:
Project
No.
122­
102.
(
Unpublished
study
received
Jul
19,
1982
under
92­
35;
prepared
by
Truslow
Farms,
Inc.,
submitted
by
Tenneco
Chemical,
Inc.,
Piscataway,
NJ;
CDL:
247878­
C)

129008
Beavers,
J.;
Jaber,
M.;
Joiner,
G.;
et
al.
(
1983)
Acute
Oral
LD50­­
Mallard
Duck:
Nuosept
95:
Project
No.
122­
105.
Final
rept.
(
Unpublished
study
received
Jun
23,
1983
under
1100­
82;
prepared
by
Wildlife
International
Ltd.,
submitted
by
Nuodex,
Inc.,
Piscataway,
NJ;
CDL:
250533­
A)

129009
LeBlanc,
G.;
Surprenant,
D.
(
1983)
Acute
Toxicity
of
Nuosept
95
to
the
Water
Flea
...:
Report
#
BW­
83­
2­
1366.
(
Unpublished
study
received
Jun
23,
1983
under
1100­
82;
prepared
by
EG
&
G
Bionomics,
submitted
by
Nuodex,
Inc.,
Piscataway,
NJ;
CDL:
250533­
B)

129010
Ward,
G.;
Hodgson,
J.
(
1983)
Acute
Toxicity
of
Nuosept
95
to
Sheepshead
Minnows
...:
Report
No.
BP­
83­
5­
56.
(
Unpublished
study
received
Jun
23,
1983
under
1100­
82;
prepared
by
EG
&
G
Bionomics,
submitted
by
Nuodex,
Inc.,
Piscataway,
NJ;
CDL:
250533­
C)

129011
Ward,
G.;
Hodgson,
J.
(
1983)
Acute
Toxicity
of
Nuosept
95
to
Mysid
Shrimp
...:
Report
No.
BP­
83­
3­
41.
(
Unpublished
study
received
Jun
23,
1983
under
1100­
82;
prepared
by
EG
&
G
Bionomics,
submitted
by
Nuodex,
Inc.,
Piscataway,
NJ,
CDL:
250533­
D)
50
129012
Ward,
G.;
Hodgson,
J.
(
1983)
Acute
Toxicity
of
Nuosept
95
to
Embryos­
larvae
of
Eastern
Oysters
...:
Report
No.
BP­
83­
6­
64.
(
Unpublished
study
received
Jun
23,
1983
under
1100­
82;
prepared
by
EG
&
G
Bionomics,
submitted
by
Nuodex,
Inc.,
Piscataway,
NJ;
CDL:
250533­
E)

41537501
Smith,
J.;
Masters,
R.;
John,
D.;
et
al.
(
1990)
A
Study
of
the
Effect
of
Nuosept
95
on
Pregnancy
of
the
Rat:
Report
No.
NDX
3/
88962.
Unpublished
study
prepared
by
Huntingdon
Research
Centre
Ltd.
122
p.

41641601
Dilley,
J.
(
1990)
Acute
Oral
Toxicity
of
Nuosept
95
in
Rats:
Interim
Progress
Report:
Lab
Project
Number:
LSC­
8470.
Unpublished
study
prepared
by
SRI
International.
11
p.

41641602
Hershman,
R.
(
1984)
Summary
of
Results
of
a
Primary
Eye
Irritation
Study,
Rabbit:
Lab
Project
Number:
84­
3988A.
Unpublished
study
prepared
by
Biosearch
Inc.
9
p.

41641603
Unwin,
S.
(
1983)
Primary
Dermal
Irritation
Test
on
Nuosept
95
in
New
Zealand
White
Albino
Rabbits:
Final
Report:
Lab
Project
Number:
7808­
E/
1.
Unpublished
study
prepared
by
Midwest
Research
Institute.
11
p.

41641605
Elliot,
P.;
Street,
A.;
Gibson,
W.;
et
al.
(
1985)
Twenty­
One
Day
Dermal
Toxicity
Study
in
Rabbits
with
Nuosept
95/
Nuosept
C:
Lab
Project
Number:
NDX
1­
84955­
SB.
Unpublished
study
prepared
by
Huntingdon
Research
Centre.
103
p.

41641606
Sasmore,
D.;
Tyson,
C.
(
1980)
Effect
of
Nuosept
95
in
Rats:
90­
Day
Toxicity
Study­
Contains
Dose
Range
Study
for
Dominant
Lethal
Study:
Final
Report:
Lab
Project
Number:
LSC­
8654.
Unpublished
study
prepared
by
SRI
Int.
72
p.

41671801
Liggett,
M.;
McRae,
L.
(
1990)
Acute
Dermal
Toxicity
to
Rabbits
of
Nuosept
95:
Final
Report:
Lab
Project
Number:
90591D/
NDX
8/
AC.
Unpublished
study
prepared
by
Huntingdon
Research
Centre
Ltd.
14
p.

41684801
Hakin,
B.;
Rodgers,
M.;
Anderson,
A.;
et
al.
(
1990)
Nuosept
95:
LC­
50
to
Bobwhite
Quail:
Lab
Project
Number:
NDX9/
901288.
Unpublished
study
prepared
by
Huntingdon
Research
Centre
Ltd.
30
p.

41699001
Hodgson,
J.
(
1988)
A
Study
of
the
Effect
of
Nuosept
95
on
Pregnancy
of
the
Rat:
Lab
Project
Number:
HRC
NDX
3/
88962.
Unpublished
study
prepared
by
Huntingdon
Research
Centre,
Ltd.
122
p.

41728601
O'Loughlin,
K.
(
1990)
Measurement
of
Micronuclei
in
Bone
Marrow
Erythrocytes
of
Swiss­
Webster
Mice
Following
Two
Treatments
with
Nuosept
95:
Lab
Project
Number:
1556­
C01­
90.
Unpublished
study
prepared
by
SRI
International.
36
p.
51
42587501
Popendorf,
W.;
Selim,
M.;
Kross,
B.
(
1992)
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study:
Second
Replacement
to
MRID
41761201:
Lab
Project
Number:
Q626.
Unpublished
study
prepared
by
The
University
of
Iowa.
316
p.

42650901
Cholakis,
J.;
Sprinz,
H.
(
1983)
Acute
Inhalation
Toxicity
of
Nuosept
95
in
Sprague­
Dewley
Rats:
Lab
Project
Number:
7808­
E(
1).
Unpublished
study
prepared
by
Midwest
Research
Institute.
25
p.

42711001
Hamilton,
C.
(
1993)
Measurement
of
Unscheduled
DNA
Synthesis
in
Male
Fischer­
344
Rat
Hepatocytes
Following
In­
Vivo
Treatment
with
Nuosept
95:
Lab
Project
Number:
LSC
4084­
U01­
92.
Unpublished
study
prepared
by
SRI
International.
24
p.

42720801
Rush,
D.
(
1993)
Efficacy/
Phytotoxicity
Studies
Performed
with
Monocarbamide
Dihydrogensulfate:
Lab
Project
Number:
RE­
P­
GA­
10:
RE­
P­
GA­
4:
RE­
FC­
GA­
2.
Unpublished
study
prepared
by
Unocal
Agriproducts.
123
p.

42734301
Mahoney,
D.
(
1993)
Product
Identity
(
Confidential
Statement
of
Formula):
Nuosept
95
Preservative:
Upgrade
to
MRID
41671601.
Unpublished
study
prepared
by
Huls
America,
Inc.
6
p.

42740801
Mahoney,
D.
(
1993)
Nuosept
95:
Certification
of
Limits
(
Gas
Chromatogram):
Final
Report.
Unpublished
study
prepared
by
Huls
America,
Inc.
7
p.

43060701
Hauswirth,
J.;
Davis,
C.
(
1993)
Primary
Dermal
Irritation
of
M­
Pede
Insecticide
in
Rabbits.
Unpublished
study
prepared
by
Mycogen
Corp.
6
p.

43067001
Cross,
J.
(
1993)
Aqueous
Hydrolysis
of
Nuosept
95:
Lab
Project
Number:
211S01.
Unpublished
study
prepared
by
EPL
Bio­
Analytical
Services,
Inc.
120
p.

93050015
Bentley,
R.;
Sleight,
B.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00109246.
Acute
Toxicity
of
Nuosept
95
Preservative
to
Bluegill
and
Rainbow
Trout.
Prepared
by
EG&
G,
Inc.
13
p.

93050016
LeBlanc,
G.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00129009.
Acute
Toxicity
of
NUOSEPT
95
to
the
Water
Flea
(
Daphnia
magna):
Project
No.
BW­
83­
2­
1366.
Prepared
by
EG&
G,
Bionomics.
18
p.

93050017
Haworth,
S.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088956.
Salmonella/
Mammalian­
Microsome
Plate
Incorporation
Mutagenesis
Assay:
Project
No.
601­
257­
1.
Prepared
by
EG&
G
Mason
Research
Institute.
20
p.

93050018
Lee,
C.;
Van
Goethem,
D.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
52
00088974.
Mutagenicity
Studies
on
NUOSEPT
95
Salmonella/
Microsome
Test:
Project
No.
4754­
B.
Prepared
by
Midwest
Research
Institute.
14
p.

93050019
Haworth,
S.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088957.
Bacterial
DNA
Damage/
Repair
Suspension
Assay:
Project
No.
026­
601­
257­
6.
Prepared
by
EG&
G
Mason
Research
Institute.
17
p.

93050020
Metz,
F.;
Van
Goethem,
D.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088958.
Bacterial
DNA
Repair
Assay
of
NUOSEPT
95:
Project
No.
4822­
B.
Prepared
by
Midwest
Research
Institute.
13
p.

93050021
Myhr,
B.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088959.
Evaluation
of
NUOSEPT
95
in
the
Primary
Rat
Hepatocyte
Unscheduled
DNA
Synthesis
Assay:
Project
No.
20991.
Prepared
by
Litton
Bionetics.
21
p.

93050022
Thilager,
A.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088960.
An
Evaluation
of
Carcinogenic
Potential
of
NUOSEPT
95
Employing
the
C3H/
10T
1/
2
Cell
Transformation
Assay:
Project
No.
601­
257­
8.
Prepared
by
EG&
G
Mason
Research
Institute.
23
p.

93050023
Schechtman,
L.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088961.
Activity
of
T
1597
in
an
vitro
Mammalian
Cell
Transformation
Assay
in
the
Absence
of
Exogenous
Metabolic
Activation:
Project
No.
T
1597.122.
Prepared
by
Microbiological
Associates.
22
p.

93050024
Thilager,
A.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088962.
An
Evaluation
of
Carcinogenic
Potential
of
R­
1162
(
NUOSEPT
95)
Employing
C3H/
1OT
1/
2
Cell
Transformation
System:
Project
No.
026­
205­
435­
8.
Prepared
by
EG&
G
Mason
Research
Institute.
24
p.

93050025
Thilagar,
A.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088963.
An
Evaluation
of
Carcinogenic
Potential
of
R­
1143
(
NUOSEPT
95)
Employing
C3H/
10T
1/
2
Cell
Transformation
System:
Project
No.
026­
205­
437­
8.
Prepared
by
EG&
G
Mason
Research
Institute.
24
p.

93050026
Jorgenson,
T.
(
1990)
Huls
America,
Inc.
Phase
3
Reformat
of
MRID
00088953.
Dominant
Lethal
Study
of
NUOSEPT
95:
Project
No.
LSC­
8654.
Prepared
by
SRI
International.
81
p.

2.
Open
Literature
PHED
Surrogate
Exposure
Guide.
1997.
Estimates
of
Worker
Exposure
from
the
Pesticide
Handler
Exposure
Database
Version
1.1.
May
1997.
53
3.
Website
References
Environmental
Protection
Agency
(
EPA),
2002.
ECOTOX
User
Guide:
ECOTOXicology
Database
System.
Version
3.0.
http://
www.
epa.
gov/
ecotox/.

Environmental
Protection
Agency
(
EPA),
2004.
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
Appendix
A,
Section
IIB,
pg.
81.
US
Environmental
Protection
Agency.
January
24,
2004.
http://
www.
epa.
gov/
oppfead1/
endanger/
consultation/
ecorisk­
overview.
pdf.

Environmental
Protection
Agency
(
EPA),
2005a.
Chemical
Screening
Tool
for
Exposures
and
Environmental
Releases.
February
2005.
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
chemsteer.
htm.

Environmental
Protection
Agency
(
EPA),
2005b.
Estimation
Program
Interface
(
EPI)
Suite.
US
Environmental
Protection
Agency.
http://
www.
epa.
gov/
oppt/
exposure/
docs/
episuite.
htm.

Food
and
Drug
Administration
(
US
FDA),
Center
for
Food
Safety
&
Applied
Nutrition
(
CFSAN).
2002.
Preparation
of
Food
Contact
Notifications
and
Food
Additive
Petitions
for
Food
Contact
Substances:
Chemistry
Recommendations.
April
2002.
http://
www.
cfsan.
fda.
gov/~
dms/
opa2pmnc.
html.

Food
and
Drug
Administration
(
US
FDA),
Center
for
Food
Safety
&
Applied
Nutrition
(
CFSAN).
2005.
CEDI/
ADI
Table:
Publicly
Available
Database
of
Cumulative
Estimated
Daily
Intakes
and
Acceptable
Daily
Intakes.
May
2005.
http://
www.
cfsan.
fda.
gov/~
dms/
opa­
tedi.
html.

4.
Supporting
Documents
Cinalli,
Christina,
et
al.,
1992.
A
Laboratory
Method
to
Determine
the
Retention
of
Liquids
on
the
Surface
of
Hands.
Prepared
for
Environmental
Protection
Agency,
Office
of
Pollution
Prevention
and
Toxics.
EPA
Contract
No.
68­
02­
4254.
September
1992.

Environmental
Protection
Agency
(
EPA),
1997a.
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments.
Health
Effects
Division,
Office
of
Pesticide
Programs.

Environmental
Protection
Agency
(
EPA),
1997b.
The
Use
of
Models
for
Estimating
Exposure
and
Risk
of
Antimicrobials
in
Metalworking
Fluids.
Memorandum
from
Winston
Dang.

Environmental
Protection
Agency
(
EPA),
1999.
Evaluation
of
the
Chemical
Manufacturers
Association
Antimicrobial
Exposure
Assessment
Study
(
Amended
on
December
8,
1992).
Memorandum
from
Siroos
Mostaghimi,
Ph.
D.,
Environmental
Engineer
to
Julie
Fairfax,
PM
#
36.
November
4,
1999.
54
Environmental
Protection
Agency
(
EPA),
2000.
Options
for
Revising
CEB's
Model
for
Screening
Level
Estimates
of
Dermal
Exposure.
Chemical
Engineering
Branch:
Economics,
Exposure,
and
Technology
Division,
Office
of
Pollution
Prevention
and
Toxics.
June
2000.

Environmental
Protection
Agency
(
EPA),
2001.
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments.
Office
of
Pesticide
Programs.

Environmental
Protection
Agency,
2005.
Summary
of
Antimicrobial
Standard
Operating
Procedure
(
SOP)
Assumptions
for
Residential
and
Occupational
Exposure
Assessments,
January
2005.
55
Appendix
E.
Generic
Data
Call­
In
56
Appendix
F.
Product
Specific
Data
Call­
In
57
Appendix
G.
Batching
of
Azadioxabicyclooctane
Products
for
Meeting
Acute
Toxicity
Data
Requirements
for
Reregistration
In
an
effort
to
reduce
the
time,
resources
and
number
of
animals
needed
to
fulfill
the
acute
toxicity
data
requirements
for
reregistration
of
products
containing
azadioxabicyclooctane
as
the
active
ingredient,
the
Agency
has
batched
products
which
can
be
considered
similar
for
purposes
of
acute
toxicity.
Factors
considered
in
the
sorting
process
include
each
product's
active
and
inert
ingredients
(
identity,
percent
composition
and
biological
activity),
type
of
formulation
(
e.
g.,
emulsifiable
concentrate,
aerosol,
wettable
powder,
granular,
etc.),
and
labeling
(
e.
g.,
signal
word,
use
classification,
precautionary
labeling,
etc.).
Note
that
the
Agency
is
not
describing
batched
products
as
"
substantially
similar"
since
some
products
within
a
batch
may
not
be
considered
chemically
similar
or
have
identical
use
patterns.

Using
available
information,
batching
has
been
accomplished
by
the
process
described
in
the
preceding
paragraph.
Not
with­
standing
the
batching
process,
the
Agency
reserves
the
right
to
require,
at
any
time,
acute
toxicity
data
for
an
individual
product
should
the
need
arise.

Registrants
of
products
within
a
batch
may
choose
to
cooperatively
generate,
submit
or
cite
a
single
battery
of
six
acute
toxicological
studies
to
represent
all
the
products
within
that
batch.
It
is
the
registrants'
option
to
participate
in
the
process
with
all
other
registrants,
only
some
of
the
other
registrants,
or
only
their
own
products
within
a
batch,
or
to
generate
all
the
required
acute
toxicological
studies
for
each
of
their
own
products.
If
a
registrant
chooses
to
generate
the
data
for
a
batch,
he/
she
must
use
one
of
the
products
within
the
batch
as
the
test
material.
If
a
registrant
chooses
to
rely
upon
previously
submitted
acute
toxicity
data,
he/
she
may
do
so
provided
that
the
data
base
is
complete
and
valid
by
today's
standards
(
see
acceptance
criteria
attached),
the
formulation
tested
is
considered
by
EPA
to
be
similar
for
acute
toxicity,
and
the
formulation
has
not
been
significantly
altered
since
submission
and
acceptance
of
the
acute
toxicity
data.
Regardless
of
whether
new
data
is
generated
or
existing
data
is
referenced,
registrants
must
clearly
identify
the
test
material
by
EPA
Registration
Number.
If
more
than
one
confidential
statement
of
formula
(
CSF)
exists
for
a
product,
the
registrant
must
indicate
the
formulation
actually
tested
by
identifying
the
corresponding
CSF.

In
deciding
how
to
meet
the
product
specific
data
requirements,
registrants
must
follow
the
directions
given
in
the
Data
Call­
In
Notice
and
its
attachments
appended
to
the
RED.
The
DCI
Notice
contains
two
response
forms
which
are
to
be
completed
and
submitted
to
the
Agency
within
90
days
of
receipt.
The
first
form,
"
Data
Call­
In
Response,"
asks
whether
the
registrant
will
meet
the
data
requirements
for
each
product.
The
second
form,
"
Requirements
Status
and
Registrant's
Response,"
lists
the
product
specific
data
required
for
each
product,
including
the
standard
six
acute
toxicity
tests.
A
registrant
who
wishes
to
participate
in
a
batch
must
decide
whether
he/
she
will
provide
the
data
or
depend
on
someone
else
to
do
so.
If
a
registrant
supplies
the
data
to
support
a
batch
of
products,
he/
she
must
select
one
of
the
following
options:
Developing
Data
(
Option
1),
Submitting
an
Existing
Study
(
Option
4),
Upgrading
an
Existing
Study
(
Option
5)
or
Citing
an
Existing
Study
(
Option
6).
If
a
registrant
depends
on
another's
data,
he/
she
must
choose
among:
Cost
Sharing
(
Option
2),
Offers
to
Cost
Share
(
Option
3)
or
58
Citing
an
Existing
Study
(
Option
6).
If
a
registrant
does
not
want
to
participate
in
a
batch,
the
choices
are
Options
1,
4,
5
or
6.
However,
a
registrant
should
know
that
choosing
not
to
participate
in
a
batch
does
not
preclude
other
registrants
in
the
batch
from
citing
his/
her
studies
and
offering
to
cost
share
(
Option
3)
those
studies.

Two
products
were
found
which
contain
azadioxabicyclooctane
as
the
active
ingredient.
These
products
have
been
placed
into
one
batch
in
accordance
with
the
active
and
inert
ingredients
and
type
of
formulation.

NOTE:
The
technical
acute
toxicity
values
included
in
this
document
are
for
informational
purposes
only.
The
data
supporting
these
values
may
or
may
not
meet
the
current
acceptance
criteria.

Batch
1
EPA
Registration
Number
Percentage
Active
Ingredient
1528­
28
50.0
1528­
49
50.0
59
Appendix
H.
List
of
All
Registrants
Sent
the
Data
Call­
In
International
Specialty
Products
60
Appendix
I.
List
of
Available
Related
Documents
and
Electronically
Available
Forms
Pesticide
Registration
Forms
are
available
at
the
following
EPA
internet
site:
http://
www.
epa.
gov/
opprd001/
forms/
.

Pesticide
Registration
Forms
(
These
forms
are
in
PDF
format
and
require
the
Acrobat
reader)

Instructions
1.
Print
out
and
complete
the
forms.
(
Note:
Form
numbers
that
are
bolded
can
be
filled
out
on
your
computer
then
printed.)

2.
The
completed
form(
s)
should
be
submitted
in
hardcopy
in
accord
with
the
existing
policy.

3.
Mail
the
forms,
along
with
any
additional
documents
necessary
to
comply
with
EPA
regulations
covering
your
request,
to
the
address
below
for
the
Document
Processing
Desk.

DO
NOT
fax
or
e­
mail
any
form
containing
`
Confidential
Business
Information'
or
`
Sensitive
Information.'

If
you
have
any
problems
accessing
these
forms,
please
contact
Nicole
Williams
at
(
703)
308­
5551
or
by
e­
mail
at
williams.
nicole@
epamail.
epa.
gov.

The
following
Agency
Pesticide
Registration
Forms
are
currently
available
via
the
internet
at
the
following
locations:
8570­
1
Application
for
Pesticide
Registration/
Amendment
http://
www.
epa.
gov/
opprd001/
forms/
8570­
1.
pdf
8570­
4
Confidential
Statement
of
Formula
http://
www.
epa.
gov/
opprd001/
forms/
8570­
4.
pdf
8570­
5
Notice
of
Supplemental
Registration
of
Distribution
of
a
Registered
Pesticide
Product
http://
www.
epa.
gov/
opprd001/
forms/
8570­
5.
pdf
8570­
17
Application
for
an
Experimental
Use
Permit
http://
www.
epa.
gov/
opprd001/
forms/
8570­
17.
pdf
8570­
25
Application
for/
Notification
of
State
Registration
of
a
Pesticide
To
Meet
a
Special
Local
Need
http://
www.
epa.
gov/
opprd001/
forms/
8570­
25.
pdf
8570­
27
Formulator's
Exemption
Statement
http://
www.
epa.
gov/
opprd001/
forms/
8570­
27.
pdf
8570­
28
Certification
of
Compliance
with
Data
Gap
Procedures
http://
www.
epa.
gov/
opprd001/
forms/
8570­
28.
pdf
8570­
30
Pesticide
Registration
Maintenance
Fee
Filing
http://
www.
epa.
gov/
opprd001/
forms/
8570­
30.
pdf
8570­
32
Certification
of
Attempt
to
Enter
into
an
Agreement
with
other
Registrants
for
Development
of
Data
http://
www.
epa.
gov/
opprd001/
forms/
8570­
32.
pdf
8570­
34
Certification
with
Respect
to
Citations
of
Data
(
in
PR
Notice
98­
5)
http://
www.
epa.
gov/
opppmsd1/
PR_
Notices/
pr98­
5.
pdf
8570­
35
Data
Matrix
(
in
PR
Notice
98­
5)
http://
www.
epa.
gov/
opppmsd1/
PR_
Notices/
pr98­
5.
pdf
8570­
36
Summary
of
the
Physical/
Chemical
Properties
(
in
PR
Notice
98­
1)
http://
www.
epa.
gov/
opppmsd1/
PR_
Notices/
pr98­
1.
pdf
8570­
37
Self­
Certification
Statement
for
the
Physical/
Chemical
Properties
(
in
PR
Notice
98­
1)
http://
www.
epa.
gov/
opppmsd1/
PR_
Notices/
pr98­
1.
pdf
61
Pesticide
Registration
Kit
www.
epa.
gov/
pesticides/
registrationkit/.

Dear
Registrant:

For
your
convenience,
we
have
assembled
an
online
registration
kit
that
contains
the
following
pertinent
forms
and
information
needed
to
register
a
pesticide
product
with
the
U.
S.
Environmental
Protection
Agency's
Office
of
Pesticide
Programs
(
OPP):

1.
The
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA)
as
Amended
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.

2.
Pesticide
Registration
(
PR)
Notices
a.
83­
3
Label
Improvement
Program 
Storage
and
Disposal
Statements
b.
84­
1
Clarification
of
Label
Improvement
Program
c.
86­
5
Standard
Format
for
Data
Submitted
under
FIFRA
d.
87­
1
Label
Improvement
Program
for
Pesticides
Applied
through
Irrigation
Systems
(
Chemigation)

e.
87­
6
Inert
Ingredients
in
Pesticide
Products
Policy
Statement
f.
90­
1
Inert
Ingredients
in
Pesticide
Products;
Revised
Policy
Statement
g.
95­
2
Notifications,
Non­
notifications,
and
Minor
Formulation
Amendments
h.
98­
1
Self
Certification
of
Product
Chemistry
Data
with
Attachments.
(
This
document
is
in
PDF
format
and
requires
the
Acrobat
reader.)

Other
PR
Notices
can
be
found
at
http://
www.
epa.
gov/
opppmsd1/
PR_
Notices.

3.
Pesticide
Product
Registration
Application
Forms
(
These
forms
are
in
PDF
format
and
will
require
the
Acrobat
reader.)

a.
EPA
Form
No.
8570­
1,
Application
for
Pesticide
Registration/
Amendment
b.
EPA
Form
No.
8570­
4,
Confidential
Statement
of
Formula
c.
EPA
Form
No.
8570­
27,
Formulator's
Exemption
Statement
d.
EPA
Form
No.
8570­
34,
Certification
with
Respect
to
Citations
of
Data
e.
EPA
Form
No.
8570­
35,
Data
Matrix
62
4.
General
Pesticide
Information
(
Some
of
these
forms
are
in
PDF
format
and
will
require
the
Acrobat
reader.)

a.
Registration
Division
Personnel
Contact
List
b.
Biopesticides
and
Pollution
Prevention
Division
(
BPPD)
Contacts
c.
Antimicrobials
Division
Organizational
Structure/
Contact
List
d.
53
F.
R.
5952,
Pesticide
Registration
Procedures;
Pesticide
Data
Requirements
(
PDF
format)

e.
40
CFR
Part
156,
Labeling
Requirements
for
Pesticides
and
Devices
(
PDF
format)

f.
40
CFR
Part
158,
Data
Requirements
for
Registration
(
PDF
format)

g.
50
F.
R.
48833,
Disclosure
of
Reviews
of
Pesticide
Data
(
November
27,
1985)

Before
submitting
your
application
for
registration,
you
may
wish
to
consult
some
additional
sources
of
information.
These
include:

1.
The
Office
of
Pesticide
Programs'
Web
Site.

2.
The
booklet
"
General
Information
on
Applying
for
Registration
of
Pesticides
in
the
United
States",
PB92­
221811,
available
through
the
National
Technical
Information
Service
(
NTIS)
at
the
following
address:

National
Technical
Information
Service
(
NTIS)
5285
Port
Royal
Road
Springfield,
VA.
22161
The
telephone
number
for
NTIS
is
(
703)
605­
6000.
Please
note
that
EPA
is
currently
in
the
process
of
updating
this
booklet
to
reflect
the
changes
in
the
registration
program
resulting
from
the
passage
of
the
FQPA
and
the
reorganization
of
the
Office
of
Pesticide
Programs.
We
anticipate
that
this
publication
will
become
available
during
the
Fall
of
1998.
Their
Web
site
is
www.
NTIS.
gov.

3.
The
National
Pesticide
Information
Retrieval
System
(
NPIRS)
of
Purdue
University's
Center
for
Environmental
and
Regulatory
Information
Systems.
This
service
does
charge
a
fee
for
subscriptions
and
custom
searches.
You
can
contact
NPIRS
by
telephone
at
(
765)
494­
6614
or
through
their
Web
site.

4.
The
National
Pesticide
Telecommunications
Network
(
NPTN)
can
provide
information
on
active
ingredients,
uses,
toxicology,
and
chemistry
of
pesticides.
You
can
contact
NPTN
by
telephone
at
(
800)
858­
7378
or
through
their
Web
site:
ace.
orst.
edu/
info/
nptn.
63
The
Agency
will
return
a
notice
of
receipt
of
an
application
for
registration
or
amended
registration,
experimental
use
permit,
or
amendment
to
a
petition
if
the
applicant
or
petitioner
encloses
with
his
submission
a
stamped,
self­
addressed
postcard.
The
postcard
must
contain
the
following
entries
to
be
completed
by
OPP:

Date
of
receipt
EPA
identifying
number
Product
Manager
assignment
Other
identifying
information
may
be
included
by
the
applicant
to
link
the
acknowledgment
of
receipt
to
the
specific
application
submitted.
EPA
will
stamp
the
date
of
receipt
and
provide
the
EPA
identifying
File
Symbol
or
petition
number
for
the
new
submission.
The
identifying
number
should
be
used
whenever
you
contact
the
Agency
concerning
an
application
for
registration,
experimental
use
permit,
or
tolerance
petition.
To
assist
us
in
ensuring
that
all
data
you
have
submitted
for
the
chemical
are
properly
coded
and
assigned
to
your
company,
please
include
a
list
of
all
synonyms,
common
and
trade
names,
company
experimental
codes,
and
other
names
which
identify
the
chemical
(
including
"
blind"
codes
used
when
a
sample
was
submitted
for
testing
by
commercial
or
academic
facilities).
Please
provide
a
CAS
number
if
one
has
been
assigned.
64
