Document ID: EPA-HQ-OPP-2005-0525-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-05T04:00Z

Page
1
of
24
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
03­
NOV­
2005
SUBJECT:
PP#:
4E6834.
Novaluron
in/
on
Brassica,
head
and
stem,
subgroup
5A.
Health
Effects
Division
(
HED)
Risk
Assessment.
DP#:
313322.
PC
Code:
124002.
Decision#:
353816.

FROM:
Sarah
J.
Levy,
M.
S.,
Chemist
Mary
Clock­
Rust,
Biologist
Pramod
Terse,
Ph.
D.,
Toxicologist
Registration
Action
Branch
1
(
RAB1)/
HED
(
7509C)

THROUGH:
P.
V.
Shah,
Ph.
D.,
Branch
Senior
Scientist
RAB1/
HED
(
7509C)

TO:
Dan
Kenny
(
PM
Team
01)
Registration
Division
(
RD;
7505C)

The
HED
of
the
Office
of
Pesticide
Programs
(
OPP)
is
charged
with
estimating
the
risk
to
human
health
from
exposure
to
pesticides.
The
RD
of
OPP
has
requested
that
HED
evaluate
hazard
and
exposure
data
and
conduct
dietary,
occupational,
residential,
and
aggregate
exposure
assessments,
as
needed,
to
estimate
the
risk
to
human
health
that
will
result
from
all
registered
and
proposed
uses
of
novaluron
(
N [[[
3­
chloro­
4­[
1,1,2­
trifluoro­
2­(
trifluoromethoxy)
ethoxy]
phenyl]
amino]
carbonyl]­
2,6­
difluorobenzamide).
A
summary
of
the
findings
and
an
assessment
of
human
risk
resulting
from
the
registered
and
proposed
tolerances
for
novaluron
is
provided
in
this
document.
The
risk
assessment,
residue
chemistry
data
review,
and
dietary
risk
assessment
were
provided
by
Sarah
Levy
(
RAB1),
the
hazard
characterization
by
Pramod
Terse
(
RAB1),
the
occupational/
residential
exposure
assessment
by
Mary
Clock­
Rust
(
RAB1),
and
the
drinking
water
assessment
by
James
Hetrick
of
the
Environmental
Fate
and
Effects
Division
(
EFED).

NOTE:
HED
completed
a
Section
3
risk
assessment
for
the
use
of
novaluron
in/
on
cotton,
pome
fruit
and
potato
(
Memo,
M.
Clock­
Rust,
et
al.,
25­
MAR­
2004;
DP#
295824).
This
document
contains
only
those
aspects
of
the
risk
assessment
which
are
affected
by
the
addition
of
the
proposed
novaluron
use.
Page
2
of
24
Recommendation
for
Tolerances
and
Registration
The
HED
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
requested
a
28­
day
inhalation
toxicity
study
as
a
condition
of
registration.
However,
based
on
the
low
volatility
and
low
inhalation
toxicity
(
Category
IV)
of
novaluron
and
inhalation
margins
of
exposure
(
MOEs)
>
1000
for
the
proposed
uses
in
this
risk
assessment,
novaluron
qualifies
for
a
waiver
of
the
28­
day
inhalation
toxicity
study
for
the
proposed
uses
[
HED
Standard
Operating
Procedure
(
SOP)
2002.01:
Guidance:
Waiver
Criteria
for
Multiple­
Exposure
Inhalation
Toxicity
Studies,
15­
AUG­
2002].
The
requirement
for
the
28­
day
inhalation
toxicity
study
is
waived
for
this
action
only.
If
in
the
future,
requests
for
new
uses
or
formulations
are
submitted
that
may
result
in
a
significant
change
in
either
the
toxicity
profile
or
exposure
scenarios,
HED
will
reconsider
this
data
requirement.

Provided
Sections
B
and
F
are
submitted,
HED
concludes
that
the
toxicological
and
residue
chemistry
databases,
as
well
as
the
aggregate
risk
assessments,
support
conditional
registration
of
the
requested
new
uses
and
establishment
of
the
following
permanent
tolerance
for
residues
of
novaluron
per
se
as
follows:

Brassica,
head
and
stem,
subgroup
5A
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
0.50
ppm
HED
recommends
that
conversion
of
conditional
registration
to
unconditional
registration
may
be
considered
upon
submission
of
the
following
residue
chemistry
data:

°
Radiovalidation
of
the
gas
chromatography
(
GC)/
electron­
capture
detection
(
ECD)
plant
analytical
method,
using
radiolabeled
samples
from
the
metabolism
studies,
in
order
to
determine
whether
the
method
adequately
extract
aged
(
weathered)
residues
of
novaluron.

°
An
interference
study
is
also
required
to
determine
whether
other
pesticides
registered
on
the
same
commodities
interfere
with
the
determination
of
novaluron;
an
interference
study
may
be
waived
if
a
specific
single
analyte
confirmatory
method
is
submitted.
Page
3
of
24
Table
of
Contents
1.0
EXECUTIVE
SUMMARY
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2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
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3.0
HAZARD
CHARACTERIZATION
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3.1
Endocrine
Disruption
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4.0
EXPOSURE
ASSESSMENT
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23
4.1
Summary
of
Proposed
Uses
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4.2
Dietary
Exposure/
Risk
Pathway
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13
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23
4.3
Water
Exposure
and
Risk
Pathway
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Page
16
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23
4.4
Dietary­
Exposure
Analysis
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17
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4.5
Residential
Exposure
and
Risk
Pathway
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18
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23
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
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18
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6.0
CUMULATIVE
RISK
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7.0
OCCUPATIONAL
EXPOSURE
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7.1
Occupational
Handler
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7.2
Occupational
Postapplication
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7.3
Incident
Data
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22
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8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
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8.1
Toxicology
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8.2
Residue
Chemistry
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8.3
Occupational/
Residential
Exposure
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Page
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23
Page
4
of
24
1.0
EXECUTIVE
SUMMARY
Under
Section
3
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(
FIFRA),
as
amended,
Makhteshim­
Agan
of
North
America
(
MANA),
Inc.
has
applied
for
registration
of
the
active
insecticidal
ingredient
novaluron
for
use
on
Brassica,
head
and
stem,
subgroup
5A.
Novaluron
is
currently
registered
for
use
on
cotton;
pome
fruit;
Vegetables,
tuberous
and
corm,
group
1C;
and
greenhouse/
shadehouse
grown
ornamental
plants.
Novaluron
tolerances
have
been
established
in
40
CFR
§
180.598
for
plant
and
livestock
commodities
and
are
expressed
in
terms
of
novaluron
per
se.
All
uses
for
novaluron,
either
proposed
or
existing,
are
agricultural
or
commercial
in
nature.
No
residential
uses
are
proposed,
nor
are
any
of
the
uses
expected
to
result
in
recreational
exposure.

Novaluron,
a
benzoylphenyl
urea
compound,
is
a
pesticide
chemical
belonging
to
the
class
of
insecticides
called
insect
growth
regulators.
Novaluron
slowly
kills
the
insects
over
a
period
of
a
few
days
by
disrupting
cuticle
formation
and
deposition
causing
insect
mortality
during
molting.
This
memorandum
serves
as
HED's
estimate
of
exposure
and
risk
resulting
from
the
proposed
uses.

Hazard
Characterization
The
toxicological
database
for
novaluron
is
adequate
to
support
Section
3
registration
and
permanent
tolerances.

Novaluron
has
low
acute
toxicity
via
the
oral
(
Toxicity
Category
IV),
dermal
(
Toxicity
Category
III)
and
inhalation
routes
(
Toxicity
Category
IV).
No
ocular
(
Toxicity
Category
IV)
or
dermal
irritation
(
Toxicity
Category
IV)
was
noted.
Novaluron
is
not
a
dermal
sensitizer.

In
subchronic
and
chronic
toxicity
studies,
novaluron
primarily
produced
hematotoxic
effects
such
as
methemoglobinemia,
decreased
hemoglobin,
decreased
hematocrit,
decreased
red
blood
corpuscles
(
RBCs
or
erythrocytes)
associated
with
increased
erythropoiesis.

The
rat
and
rabbit
developmental
toxicity
studies
were
tested
up
to
the
limit
doses
that
produced
no
maternal
and/
or
developmental
toxicity.
In
the
two­
generation
reproductive
toxicity
study,
both
maternal
and
offspring
toxicity
were
evidenced
by
spleenomegaly,
whereas
reproductive
toxicity
was
observed
only
in
males
as
evidenced
by
decreases
in
epididymal
sperm
counts
and
increased
age
at
preputial
separation
in
the
F
1
generation.

Acute/
subchronic
neurotoxicity
screening
batteries
were
performed
using
novaluron
in
rats.
Neurotoxic
effects
of
novaluron
were
evidenced
by
clinical
signs
(
piloerection,
fast/
irregular
breathing),
functional
observation
battery
(
FOB)
parameters
(
head
swaying,
abnormal
gait)
and
neuropathology
(
sciatic
and
tibial
nerve
degeneration
only
at
limit
dose
(
2000
mg/
kg/
day).
No
signs
of
neurotoxicity
or
neuropathology
were
observed
in
the
subchronic
neurotoxicity
study
in
rats
at
doses
up
to
1752
mg/
kg/
day
in
males
and
2000
mg/
kg/
day
in
females.
Therefore,
HED's
Page
5
of
24
HIARC
concluded
that
there
is
not
a
concern
for
neurotoxicity
resulting
from
exposure
to
novaluron.

There
was
no
concern
for
mutagenic
activity
as
indicated
by
several
mutagenicity
studies
such
as
a
bacterial
(
Salmonella,
E.
coli)
reverse
mutation
assay,
an
in
vitro
mammalian
chromosomal
aberration
assay,
an
in
vivo
mouse
bone­
marrow
micronucleus
assay
and
bacterial
DNA
damage
or
repair
assay.
There
was
no
evidence
of
carcinogenic
potential
in
either
the
rat
or
mouse
carcinogenicity
studies.
Therefore,
novaluron
was
classified
as
"
not
likely
to
be
carcinogenic
to
humans."

Dose
Response
and
Endpoint
Selection
The
oral
acute
reference
dose
(
aRfD)
for
the
general
population,
including
infants
and
children,
was
not
established
since
an
endpoint
of
concern
attributable
to
a
single
dose
was
not
identified.
The
chronic
reference
dose
(
cRfD)
of
0.011
mg/
kg/
day
was
determined
on
the
basis
of
the
chronic
carcinogenicity
study
in
rat.
An
uncertainty
factor
(
UF)
of
100
(
10­
fold
for
interspecies
extrapolation
and
10­
fold
for
intraspecies
variability)
was
applied
to
the
no­
observed­
adverseeffect
level
(
NOAEL)
of
1.1
mg/
kg/
day
to
derive
the
cRfD.
The
lowest­
observed­
adverse­
effectlevel
(
LOAEL)
of
30.6
mg/
kg/
day
was
based
on
evidence
of
RBC
damage
and
turnover
resulting
in
a
regenerative
anemia.
The
Food
Quality
Protection
Act
(
FQPA)
Safety
Factor
(
SF)
of
1X
is
applicable
for
chronic
dietary
risk
assessment.
Therefore,
the
cPAD
is
0.011
mg/
kg/
day.

In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(
JUL­
1999),
novaluron
is
classified
as
"
not
likely
to
be
carcinogenic
to
humans"
based
on
the
lack
of
evidence
for
carcinogenicity
in
mice
and
rats.

The
HIARC
concluded
that
no
special
FQPA
SF
is
needed
(
i.
e.,
1X)
since
there
are
no
residual
uncertainties
for
pre­
and/
or
post­
natal
toxicity.
The
decision
was
based
on
a
lack
of
increased
susceptibility
in
the
rat
and/
or
rabbit
developmental
toxicity
studies
at
levels
up
to
the
limit
dose.
Also,
no
increased
qualitative
and/
or
quantitative
evidence
of
increased
susceptibility
was
found
following
pre/
post­
natal
exposure
in
a
2­
generation
reproduction
study
in
rats.

HIARC
met
on
16­
DEC­
2003
to
select
endpoints
for
risk
assessment
and
to
evaluate
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
novaluron
according
to
the
FEB­
2002
OPP
10X
guidance
document.
This
was
a
re­
evaluation
of
the
toxicology
database
subsequent
to
the
initial
evaluation
by
the
HIARC
on
07­
JUN­
2001
(
TXR#
014682).
The
special
FQPA
SF
was
reduced
to
1X
based
on
toxicological
considerations
by
the
HIARC
(
16­
DEC­
2003;
TXR
#
0052361),
the
conservative
residue
assumptions
used
in
the
dietary
and
residential
exposure
risk
assessments,
and
the
completeness
of
the
residue
chemistry
and
conservative
drinking
water
assessment
evaluated
by
the
risk
assessment
team.
Page
6
of
24
A
10%
dermal­
absorption
factor
was
based
on
an
acceptable
dermal­
absorption
study
in
rats
in
which
the
maximum
total
absorbed
dose
(
expressed
as
percent
of
administered
dose)
ranged
from
approximately
0.5%
to
10%
of
the
applied
dose.
The
level
of
concern
(
LOC)
for
residential
dermal
exposures
and
occupational
dermal
and
inhalation
exposures
are
for
MOEs
<
100.
Endpoints
applicable
to
risk
assessments
performed
for
novaluron
in
this
document
are
summarized
in
the
table
below.

Exposure
Scenario
Dose
Endpoint
Study/
Effect
Chronic
dietary
NOAEL
=
1.1
mg/
kg/
day
cRfD
and
cPAD
=
0.011
mg/
kg/
day
Combined
chronic
toxicity/
carcinogenicity
feeding
study­
rat­
Erythrocyte
damage
and
turnover
resulting
in
a
regenerative
anemia
at
the
LOAEL
of
30.6
mg/
kg/
day.

Intermediate­
term
dermal
(
10%
absorption
rate)
NOAEL
=
4.38
mg/
kg/
day
Target
MOE
=
100
(
residential
and
occupational)
90­
day
feeding
study­
rat­
clinical
chemistry
and
histopathology
at
the
LOAEL
of
8.64
mg/
kg/
day
Short­
term
inhalation
Intermediate­
term
inhalation
Residues
of
Concern
The
HED
Metabolism
Assessment
and
Review
Committee
(
MARC)
concluded
that
for
tolerance
and
risk
assessment
purposes,
novaluron
per
se
is
the
only
residue
of
concern
in
plant
and
livestock
matrices,
and
rotational
crops.
In
drinking
water,
the
MARC
concluded
that
parent
and
degradates
chlorophenyl
urea
(
1­[
3­
chloro­
4­(
1,1,2­
trifluoro­
2­
trifluoromethoxyethoxy)
phenyl]
urea)
and
chloroaniline
(
3­
chloro­
4­(
1,1,2­
trifluoro­
2­
trifluoromethoxyethoxy)
aniline)
are
the
residues
of
concern
for
risk
assessment
purposes.

Chronic
Dietary
Exposure
Estimates
A
chronic
dietary
risk
assessment
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
2.03).
The
chronic
dietary
assessment
conducted,
was
an
update
of
the
previous
dietary
assessment
conducted
in
2004;
i.
e.,
the
current
commodities
associated
with
this
petition
were
added
at
the
HED­
recommended
tolerance
level
to
the
last
dietary
assessment.
Estimated
drinking
water
concentrations
(
EDWCs),
provided
by
EFED,
were
included
in
this
assessment
as
well.
In
the
last
dietary
assessment,
the
chronic
analysis
assumed
100%
crop
treated
for
all
commodities;
incorporated
average
field
trial
residues;
empirical
processing
factors
for
apple
juice
(
translated
to
pear
juice);
and
DEEM
 
(
ver
7.76)
default
processing
factors
for
the
remaining
processed
commodities.
Furthermore,
anticipated
residues
(
ARs)
were
calculated
for
meat
and
milk
commodities
and
HED­
recommended
tolerances
were
used
for
poultry
commodities
(
partially
refined,
Tier
2
analysis).
For
this
action,
the
resulting
food
exposure
estimates
were
less
than
HED's
level
of
concern
(#
71%
cPAD);
children
1­
2
years
old
were
the
most
highly
exposed
population
subgroup.
The
chronic
analysis
could
be
further
refined
through
the
following:
use
of
anticipated
market
share
data
for
the
proposed
commodities,
%
crop
treated
data
for
registered
Page
7
of
24
commodities;
preparation/
cooking
factors;
and/
or
ARs
for
poultry
commodities
and
commodities
associated
with
Brassica,
head
and
stem,
subgroup
5A.

Drinking
Water
Estimates
Concentrations
of
novaluron
and
its
chlorophenyl
urea
and
chloroaniline
degradates
in
surface
water
and
ground
water
were
estimated
by
EFED
using
modeling.
Tier
2
Pesticide
Root
Zone
Model/
Exposure
Analysis
Modeling
System
(
PRZM/
EXAMS)
modeling
was
performed
to
estimate
drinking
water
concentrations
for
novaluron
(
parent)
in
surface
water.
Tier
1
modeling
(
FQPA
Index
Reservoir
Screening
Tool
(
FIRST))
was
used
to
estimate
concentrations
of
the
chlorophenyl
urea
and
chloroaniline
degradates
in
surface
water.
For
groundwater,
the
Screening
Concentration
in
Ground
Water
(
SCI­
GROW)
model
was
used
to
predict
groundwater
concentrations
for
novaluron
and
the
chlorophenyl
urea
and
chloroaniline
degradates.

Drinking
water
estimates
from
EFED
are
meant
to
represent
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
and
groundwater
based
upon
existing
and
proposed
uses.
Chronic
estimates
for
the
terminal
degradate,
chloroaniline,
are
the
highest
(
2.61
ppb).
This
is
consistent
with
the
expected
degradation
pattern
for
novaluron.
Therefore,
the
EDWC
value
for
chloroaniline
was
used
to
assess
chronic
aggregate
risk.

Aggregate
Exposure
Scenarios
and
Risk
Conclusions
Including
all
existing
and
proposed
uses,
human­
health
risk
assessments
have
been
conducted
for
the
following
exposure
scenario
only:
chronic
dietary
exposures
(
food
+
water).
The
chronic
aggregate
exposure
and
risk
estimate
is
below
HED's
level
of
concern.
Because
there
are
no
uses
of
novaluron
that
could
result
in
residential
exposures,
this
aggregate
risk
assessment
takes
into
consideration
dietary
food
+
water
exposure
only.

Occupational
Exposure
Estimates
Handler:
Based
on
the
proposed
use
patterns,
HED
expects
the
most
highly­
exposed
occupational
pesticide
handlers
are
likely
to
be
mixer/
loaders
using
open­
pour
of
liquids
for
aerial
and
groundboom
application
and
applicators
using
open­
cab
groundboom
or
aerial
spray
equipment.
HED
performed
an
assessment
of
these
exposure
scenarios.
All
occupational
handler
risk
estimates
are
below
HED's
level
of
concern
(
MOE>
100)
provided
workers
wear
protective
gloves
when
handling
novaluron.

Post­
Application:
There
is
a
potential
for
post­
application
exposure
to
workers
from
pesticides
during
the
course
of
typical
agricultural
activities.
For
the
current
action,
intermediate­
term
postapplication
dermal
exposure
was
assessed
using
conservative
assumptions
for
the
proposed
uses.
Post­
application
inhalation
exposure
is
considered
to
be
negligible.
Page
8
of
24
To
make
a
conservative
estimate
of
post­
application
exposure
based
on
the
proposed
crop
uses,
HED
chose
hand
harvesting
Brassica
with
a
transfer
coefficient
(
TC)
of
5,000
cm2/
hr.
The
resulting
intermediate­
term
dermal
MOE
of
440
does
not
exceed
HED's
level
of
concern.

Restricted­
Entry
Interval
(
REI):
The
proposed
Diamond
0.83
(
head
and
stem
Brassica)
label
carries
a
12­
hour
REI.
Novaluron
falls
into
Category
IV
for
acute
dermal
toxicity,
primary
eye
irritation
and
primary
skin
irritation.
Therefore,
an
interim
worker
protection
standard
(
WPS)
REI
of
12
hours
is
adequate
to
protect
agricultural
workers
from
post­
application
exposures
to
novaluron.

Recommendation
for
Tolerances
and
Registration
The
HED
HIARC
requested
a
28­
day
inhalation
toxicity
study
as
a
condition
of
registration.
However,
based
on
the
low
volatility
and
low
inhalation
toxicity
(
Category
IV)
of
novaluron
and
inhalation
MOEs
>
1000
for
the
proposed
uses
in
this
risk
assessment,
novaluron
qualifies
for
a
waiver
of
the
28­
day
inhalation
toxicity
study
for
the
proposed
uses
[
HED
SOP
2002.01:
Guidance:
Waiver
Criteria
for
Multiple­
Exposure
Inhalation
Toxicity
Studies,
15­
AUG­
2002].
The
requirement
for
the
28­
day
inhalation
toxicity
study
is
waived
for
this
action
only.
If
in
the
future,
requests
for
new
uses
or
formulations
are
submitted
that
may
result
in
a
significant
change
in
either
the
toxicity
profile
or
exposure
scenarios,
HED
will
reconsider
this
data
requirement.

Provided
Sections
B
and
F
are
submitted,
HED
concludes
that
the
toxicological
and
residue
chemistry
databases,
as
well
as
the
aggregate
risk
assessments,
support
conditional
registration
of
the
requested
new
uses
and
establishment
of
the
following
permanent
tolerance
for
residues
of
novaluron
per
se
as
follows:

Brassica,
head
and
stem,
subgroup
5A
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
0.50
ppm
HED
recommends
that
conversion
of
conditional
registration
to
unconditional
registration
may
be
considered
upon
submission
of
the
following
residue
chemistry
data:

°
Radiovalidation
of
the
GC/
ECD
plant
analytical
method,
using
radiolabeled
samples
from
the
metabolism
studies,
in
order
to
determine
whether
the
method
adequately
extract
aged
(
weathered)
residues
of
novaluron.

°
An
interference
study
is
also
required
to
determine
whether
other
pesticides
registered
on
the
same
commodities
interfere
with
the
determination
of
novaluron;
an
interference
study
may
be
waived
if
a
specific
single
analyte
confirmatory
method
is
submitted.
Page
9
of
24
O
N
H
N
H
O
F
F
Cl
O
O
CF
3
F
F
F
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
The
review
of
product
chemistry
data
associated
with
this
petition
is
under
the
purview
of
RD.
All
applicable
product
chemistry
data
requirements
must
be
met
for
a
Section
3
registration
of
the
proposed
use
of
novaluron
on
Brassica,
head
and
stem,
subgroup
5A.

Table
1.
Novaluron
Nomenclature.

Compound
Chemical
Structure
Common
name
Novaluron
Trade
name
RimOn
Technical
IUPAC
name
1­[
3­
chloro­
4­(
1,1,2­
trifluoro­
2­
trifluoromethoxyethoxy)
phenyl]­
3­[
2,6­
difluorobenzoyl]
urea
CAS
name
N­[[[
3­
chloro­
4­[
1,1,2­
trifluoro­
2­(
trifluoromethoxy)
ethoxy]
phenyl]
amino]
carbonyl]­
2,6­
difluorobenzamide
CAS
#
116714­
46­
6
End­
use
product/
EP1
RimOn
7.5
WG
Insecticide
(
EPA
Reg.
No.
66222­
57)
RimOn
0.83
EC
Insecticide
(
EPA
Reg.
No.
66222­
35)
Diamond
0.83
EC
Insecticide
(
EPA
Reg.
No.
66222­
35)

1
Note
to
RD:
The
novaluron
labels
RimOn
0.83
EC
and
Diamond
0.83
EC
have
different
trade
names,
but
the
same
registration
numbers.

Table
2.
Physicochemical
Properties
of
the
Technical
Grade
of
Novaluron.

Parameter
Value
Reference
(
MRID)

Melting
point/
range
176.5
­
178.0
°
C
44961006
pH
6.5
44961005
Density
1.56
g/
cm3
at
22
°
C
44961006
Water
solubility
3
:
g/
L
at
20
°
C
44961005
44961006
Solvent
solubility
(
at
25
°
C)
8.39
mg/
L
in
n­
heptane
1.88
g/
L
in
xylene
14.5
g/
L
in
methanol
198
g/
L
in
acetone
113
g/
L
in
ethyl
acetate
0.98
g/
L
in
n­
octanol
Vapor
pressure
(
mm
Hg)
1.2
x
10­
7
44961006
Dissociation
constant,
pKa
Not
determined
due
to
low
water
solubility
44961006
Octanol/
water
partition
coefficient,
Log(
KOW)
4.3
at
25
°
C
44961006
Table
2.
Physicochemical
Properties
of
the
Technical
Grade
of
Novaluron.

Parameter
Value
Reference
(
MRID)

Page
10
of
24
UV/
visible
absorption
spectrum
Molar
absorption
coefficients
of
at
3
maximum
absorbances:
15,400
L/
mol
C
cm
at
253
µ
m
(
neutral)
9,780
L/
mol
C
cm
at
253
µ
m
(
acidic)
20,500
L/
mol
C
cm
at
263
µ
m
(
basic)
44961006
3.0
HAZARD
CHARACTERIZATION
A
detailed
hazard
characterization
for
novaluron
is
presented
in
HED's
previous
risk
assessment
(
Memo,
M.
Clock­
Rust,
et
al.,
25­
MAR­
2004
;
DP
#
295824).
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
applicable
to
this
risk
assessment
are
summarized
in
Table
3.

Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Novaluron.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
(
LOC)
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
Not
applicable
None
An
endpoint
of
concern
attributable
to
a
single
dose
was
not
identified.
An
acute
RfD
was
not
established.

Chronic
Dietary
(
all
populations)
NOAEL=
1.1
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.011
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.011
mg/
kg/
day
Combined
chronic
toxicity/
carcinogenicity
feeding
in
rat
LOAEL
=
30.6
mg/
kg/
day
based
on
erythrocyte
damage
and
turnover
resulting
in
a
regenerative
anemia.

Short­
Term
Incidental
Oral
(
1­
30
days)
NOAEL=
4.38
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
90­
day
feeding
study
in
rat
LOAEL
=
8.64
mg/
kg/
day
based
on
clinical
chemistry
(
decreased
hemoglobin,
hematocrit
and
RBC
counts)
and
histopathology
(
increased
hematopoiesis
and
hemosiderosis
in
spleen
and
liver).

Intermediate­
Term
Incidental
Oral
(
1­
6
months)
NOAEL=
4.38
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
90­
day
feeding
study
in
rat
LOAEL
=
8.64
mg/
kg/
day
based
on
clinical
chemistry
(
decreased
hemoglobin,
hematocrit
and
RBC
counts)
and
histopathology
(
increased
hematopoiesis
and
hemosiderosis
in
spleen
and
liver).
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Novaluron.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
(
LOC)
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
11
of
24
Short­
Term
Dermal
(
1­
30
days)
Not
applicable
None
No
toxicity
observed
at
the
limit
dose
in
dermal
study
and
there
were
no
developmental
toxicity
concerns
at
the
limit­
dose;
therefore,
quantification
of
short­
term
dermal
risk
is
not
necessary.

Intermediate­
Term
Dermal
(
1­
6
months)
Oral
NOAEL
=
4.38
mg/
kg/
day
(
dermal­
absorption
rate
=
10%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
90­
day
feeding
study
in
rat
LOAEL
=
8.64
mg/
kg/
day
based
on
clinical
chemistry
(
decreased
hemoglobin,
hematocrit
and
RBC
counts)
and
histopathology
(
increased
hematopoiesis
and
hemosiderosis
in
spleen
and
liver).

Long­
Term
Dermal
(>
6
months)
Oral
NOAEL=
1.1
mg/
kg/
day
(
dermal­
absorption
rate
=
10
%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Combined
chronic
toxicity/
carcinogenicity
feeding
in
rat
LOAEL
=
30.6
mg/
kg/
day
based
on
erythrocyte
damage
and
turnover
resulting
in
a
regenerative
anemia.

Short­
Term
Inhalation
(
1­
30
days)
Oral
NOAEL
=
4.38
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
90­
day
feeding
study
in
rat
LOAEL
=
8.64
mg/
kg/
day
based
on
clinical
chemistry
(
decreased
hemoglobin,
hematocrit
and
RBC
counts)
and
histopathology
(
increased
hematopoiesis
and
hemosiderosis
in
spleen
and
liver).

Intermediate­
Term
Inhalation
(
1­
6
months)
Oral
NOAEL
=
4.38
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
90­
day
feeding
study
in
rat
LOAEL
=
8.64
mg/
kg/
day
based
on
clinical
chemistry
(
decreased
hemoglobin,
hematocrit
and
RBC
counts)
and
histopathology
(
increased
hematopoiesis
and
hemosiderosis
in
spleen
and
liver).

Long­
Term
Inhalation
(>
6
months)
Oral
NOAEL=
1.1
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Combined
chronic
toxicity/
carcinogenicity
feeding
in
rat
LOAEL
=
30.6
mg/
kg/
day
based
on
erythrocyte
damage
and
turnover
resulting
in
a
regenerative
anemia.

Cancer
Not
likely
to
be
carcinogenic
to
humans
Page
12
of
24
UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no­
observed
adverse­
effect
level,
LOAEL
=
lowest­
observed
adverse­
effect
level,
PAD
=
population­
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
Page
13
of
24
3.1
Endocrine
Disruption
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."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
has
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
Agency's
EDSP
have
been
developed,
novaluron
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
EXPOSURE
ASSESSMENT
References:
residue
chemistry
summary
­
Memo,
S.
Levy,
03­
NOV­
2005;
DP#
322978
dietary
exposure
analysis
­
Memo,
S.
Levy,
03­
NOV­
2005;
DP#
322553
drinking
water
summary
­
Memo,
I.
Maher,
11­
FEB­
2004;
no
DP
Barcode
and
electronic
correspondence,
J.
Hetrick
to
M.
Rust,
03­
OCT­
2005
4.1
Summary
of
Proposed
Uses
The
petitioner
provided
a
copy
of
the
product
label
Diamond
EC
Insecticide
formulation(
0.83
lb
ai/
gal,
EPA
Reg.
No.
66222­
35);
see
Table
4
below.
(
Note
to
RD:
The
novaluron
labels
RimOn
0.83
EC
(
0.83
lb
ai/
gal,
EPA
File
Symbol
66222­
35)
and
Diamond
0.83
EC
have
different
trade
names,
but
the
same
registration
numbers.)
A
summary
of
the
proposed
uses
of
novaluron
on
head
and
stem
Brassica
vegetables
is
presented
in
Table
4.
Page
14
of
24
Table
4.
Summary
of
Novaluron
End­
Use
Products
Associated
with
the
Subject
Petitions.

Trade
Name
Reg.
No.
ai
(%
of
formulation)
Formulation
Type
Target
Crops
Target
Pests
Label
Version
Diamond
0.83
EC1
(
Novaluron
10
EC2)
66222­
35
10%
(
0.83
lb/
gal)
EC
Head
and
Stem
Brassica
Vegetables
Foliar
feeding
insects
such
as
alfalfa
and
cabbage
loopers,
armyworm,
cabbage
webworm,
corn
earworm,
cucumber
beetles,
cutworm
species,
diamondback
moth,
imported
cabbageworm,
lepidopterian
and
dipteran
leafminer,
leafhopper
species,
lygus
bugs,
flea
beetles,
onion
thrips,
southern
cabbageworm,
stink
bugs,
thrips,
vegetable
weevil,
whitefly
Label
copyright
date
of
2004
1
Crompton
Corporation
(
alternate
brand
name)
2
MANA
Table
5.
Summary
of
Directions
for
Proposed
Uses
of
Novaluron.

Trade
Name
Applic.
Timing,
Type,
and
Equip.
Applic.
Rate
(
lb
ai/
A)
Max.
No.
Applic.
per
Season
Max.
Seasonal
Applic.
Rate
(
lb
ai/
A)
PHI1
(
days)
Use
Directions
and
Limitations
Head
and
Stem
Brassica
Vegetables
Diamond
0.83
EC
(
Novaluron
10
EC)
Application
should
be
made
when
majority
of
population
is
at
egg
hatch
to
second
instar.

Ground
and
air
application
0.06­
0.078
3
0.15
7
Applications
may
be
made
using
ground
equipment
(
minimum
of
10
gal/
A)
or
aerial
(
minimum
of
2
gal/
A)
with
a
7­
to
14­
day
retreatment
interval
(
RTI).

1
PHI=
pre­
harvest
interval
4.2
Dietary
Exposure/
Risk
Pathway
Nature
of
the
Residue
­
Plants:
Adequate
metabolism
studies
for
novaluron
are
available
on
apples,
cabbage,
cotton,
and
potatoes.
These
studies
indicate
that
novaluron
is
not
extensively
metabolized
in
these
crops.
The
parent
compound,
novaluron,
was
either
the
only
residue
component
identified
or
was
the
predominant
residue
component
in
all
analyzed
plant
matrices.
The
reviewed
studies
also
indicate
novaluron,
when
foliarly
applied
during
the
vegetative
growth
stage,
is
not
readily
translocated
to
mature
apple
fruit,
potato
tubers
or
cottonseed
(
Memo,
G.
Kramer,
22­
MAR­
2004;
DP#
285474).
Based
on
these
studies,
the
MARC
determined
that
the
residue
of
concern
in
crops
for
purposes
of
tolerance
enforcement
and
risk
assessment
is
novaluron
per
se
(
Memo,
G.
Kramer
et
al.,
03­
FEB­
2004;
DP#
297646).
Page
15
of
24
Nature
of
the
Residue
­
Livestock:
HED
also
previously
concluded
that
the
nature
of
the
residue
in
livestock
is
adequately
understood
based
on
the
submitted
goat
and
poultry
metabolism
studies
(
Memo,
G.
Kramer,
22­
MAR­
2004;
DP#
285474).
The
HED
MARC
determined
that
the
residue
of
concern
in
livestock
for
purposes
of
tolerance
enforcement
and
risk
assessment
is
novaluron
per
se
(
Memo,
G.
Kramer
et
al.,
03­
FEB­
2004;
DP#
297646).

Residue
Analytical
Enforcement
Method
­
Plant:
MANA
previously
submitted
a
GC/
ECD
residue
analytical
method
for
the
analysis
of
novaluron
residues
in/
on
pome
fruit,
cabbage,
and
potato
commodities;
HED
concluded
that
the
method
was
adequate
for
gathering
data
on
novaluron.
The
method
was
adequately
validated
by
the
petitioner
and
by
an
independent
laboratory.
HED
also
concluded
that
the
method
may
be
used
for
tolerance
enforcement
pending
completion
of
a
successful
petition
method
validation
(
PMV)
by
the
Analytical
Chemistry
Branch
(
ACB)/
Biological
and
Economics
Analysis
Division
(
BEAD)
and
provided
radiovalidation
and
interference
studies
are
submitted
by
the
petitioner
(
Memo,
G.
Kramer,
22­
MAR­
2004;
DP#
285474).

ACB
concluded
that
based
upon
review
of
the
submitted
method
validation
data,
without
laboratory
validation,
the
GC/
ECD
residue
analytical
method
appears
to
be
suitable
for
food
tolerance
enforcement
in
plants
(
apples,
cabbage,
potatoes).
ACB
recommended
that
the
analytical
method
met
the
general
requirements
of
the
Residue
Chemistry
Test
Guidelines,
860.1340
for
residue
analytical
methods
to
enforce
tolerances.
Furthermore,
based
on
ACB's
review
of
the
data,
without
EPA
laboratory
validation,
the
petitioner
has
provided
evidence
of
successful
ILVs
for
the
method.
Since
the
petitioner
has
provided
adequate
method
validation
data
and
the
independent
laboratories
found
no
significant
method
deficiencies
during
the
ILVs,
ACB
recommended
that
the
analytical
methods
do
not
need
to
be
laboratory
validated
by
EPA
(
Memo,
S.
Levy,
15­
SEP­
2004;
DP#
306998).
This
method
was
sent
to
the
Food
and
Drug
Administration
(
FDA)
to
be
published
in
the
Pesticide
Analytical
Manual,
volume
II
(
PAM
II)
as
a
Letter
Method
(
Memo,
S.
Levy,
15­
SEP­
2004;
DP#
307595).
Radiovalidation
of
the
GC/
ECD
method
is
still
required,
using
radiolabeled
samples
from
the
metabolism
studies,
in
order
to
determine
whether
the
method
adequately
extract
aged
(
weathered)
residues
of
novaluron.
An
interference
study
is
still
required
to
determine
whether
other
pesticides
registered
on
the
same
commodities
interfere
with
the
determination
of
novaluron;
an
interference
study
may
be
waived
if
a
specific
single
analyte
confirmatory
method
is
submitted.

Magnitude
of
the
Residue
­
Plants:
The
following
paragraphs
are
summaries
of
the
residue
data
submitted
in
support
of
this
request.

Head
and
Stem
Brassica:
MANA
and
Crompton
Corporation
have
submitted
field
trial
data
depicting
the
magnitude
of
the
residue
of
novaluron
in/
on
head/
stem
Brassica
vegetables
(
cabbage
and
broccoli).
Twelve
field
trials
were
conducted,
six
each
for
cabbage
and
broccoli,
in
the
United
States
during
the
2002
growing
season.
Cabbage
trials
were
located
in
EPA
Regions
1
(
PA),
2
(
GA),
3
(
FL),
5
(
IL),
6
(
TX),
and
10
(
CA).
Broccoli
trials
were
located
in
EPA
Regions
Page
16
of
24
6
(
TX),
10
(
CA,
4
trials),
and
12
(
OR).
The
number
and
locations
of
field
trials
are
in
accordance
with
OPPTS
Guideline
860.1500.
At
each
trial
location,
Novaluron
10
EC
(
0.834
lb
ai/
gallon)
formulation
was
applied
three
times
to
cabbage
and
broccoli
plants
using
ground
spray
application
equipment.
The
RTI
was
5­
8
days,
beginning
at
19
to
22
days
prior
to
normal
harvest
and
ending
7
to
8
days
prior
to
normal
harvest.
The
application
rates
were
0.048­
0.052
lb
ai/
A
(
for
cabbage)
and
0.049
to
0.052
lb
a.
i./
A
(
for
broccoli)
applied
in
30­
37
GPA.
An
adjuvant
(
crop­
oil
concentrate
(
COC))
was
added
to
the
spray
mixture
for
all
applications
at
a
nominal
rate
of
1%
v/
v.

The
results
from
these
trials
show
that
the
maximum
novaluron
residues
in/
on
cabbage
with
wrapper
leaves
and
without
wrapper
leaves
were
0.481
and
<
0.051
ppm,
from
samples
treated
at
0.149
to
0.154
lb
a.
i./
A/
season
(­
1x
application
rate),
and
with
6­
8
day
RTIs
and
7­
8
day
PHIs.
The
results
from
the
broccoli
trials
show
that
the
maximum
residues
of
novaluron
in/
on
broccoli
were
0.379
ppm
from
samples
treated
at
0.149
to
0.153
lb
a.
i./
A/
season
(­
1x
application
rate),
and
with
5­
7
days
RTIs
and
7­
8
day
PHIs.
Residue
decline
data
from
cabbage
and
broccoli
show
that
novaluron
residues
decline
slightly
with
increasing
PHIs.
HED
concludes
that
the
cabbage
and
broccoli
data
support
the
proposed
use
on
Brassica,
head
and
stem,
subgroup
5A
and
a
tolerance
level
of
0.50
ppm.

Processed
Food
and
Feed:
There
are
no
processed
food/
feed
items
associated
with
head
and
stem
Brassica
vegetables;
therefore,
a
discussion
of
processed
food/
feed
is
not
germane
to
this
petition.

Confined/
Field
Accumulation
in
Rotational
Crops:
HED
previously
concluded
that
the
appropriate
plant­
back
interval
(
PBI)
for
all
non­
labeled
crops
is
30
days.
Furthermore,
the
petitioner
was
requested
to
submit
a
revised
Section
B
indicating
that
only
registered
crops
may
be
rotated
to
a
treated
field
within
30
days
of
the
final
application
(
Memo,
G.
Kramer,
22­
MAR­
2004;
DP#
285474).
This
requirement
was
not
included
on
the
Diamond
EC
label;
this
is
a
deficiency.
A
field
accumulation
study
in
rotational
crops
has
not
been
submitted.
Provided
the
petitioner
submits
a
revised
Section
B
for
the
Diamond
EC
label
indicating
that
only
registered
crops
may
be
rotated
to
a
treated
field
within
30
days
of
the
final
application,
a
field
accumulation
study
was
not
be
required
for
this
petition.

Tolerance
Summary:
Permanent
tolerances
for
novaluron
have
been
established
for
a
variety
of
commodities
under
40
CFR
§
180.598.
There
are
currently
no
established
Codex,
Canadian,
or
Mexican
maximum
residue
limits
(
MRLs)
for
novaluron.
The
appropriate
tolerance
level
was
calculated
using
the
methodology
formulated
by
the
NAFTA
MRL/
Tolerance
Harmonization
Workgroup
for
calculating
statistically­
based
pesticide
tolerances
for
plant
commodities
based
on
field
trial
residue
data.
Below
in
Table
6
is
the
proposed
and
HED­
recommended
tolerance
summary
for
novaluron.
Page
17
of
24
Table
6.
Tolerance
Summary
for
Novaluron.

Commodity
Proposed
Tolerance
(
ppm)
HED­
Recommended
Tolerance
(
ppm)
Comments
(
correct
commodity
definition)

Brassica,
head
and
stem,
subgroup
5A
0.5
0.5
Brassica,
head
and
stem,
subgroup
5A
4.3
Water
Exposure
and
Risk
Pathway
The
following
information
concerning
the
environmental
fate
and
drinking
water
assessment
of
novaluron
was
provided
by
EFED
(
Memo,
M.
Janson,
et
al.,
06­
MAY­
2005;
DP#
307166
and
electronic
correspondence,
J.
Hetrick
to
M.
Rust,
03­
OCT­
2005).
At
the
present
time,
surface
and
ground
water
monitoring
data
are
not
available
for
novaluron.

The
HED
MARC
concluded
that
parent
and
the
chlorophenyl
urea
and
chloroaniline
degradates
are
residues
of
potential
concern
to
be
included
in
the
drinking
water
assessment.

Modeling
and
Drinking
Water
Estimates
Monitoring
data
for
novaluron,
chlorophenyl
urea
and
chloroaniline
in
surface
water
and
ground
water
were
not
found.
Novaluron
is
not
included
in
the
USGS
National
Water­
Quality
Assessment
(
NAWQA)
Program,
the
Pesticides
in
Ground
Water
Database
(
USEPA,
1992),
and
it
was
not
an
analyte
in
the
National
Pesticide
Survey
(
USEPA,
1990).
Monitoring
data
are
not
available
for
novaluron
or
its
chlorophenyl
urea
and
chloroaniline
degradates,
in
surface
water
or
ground
water.
Concentrations
in
surface
water
and
ground
water
were
estimated
using
modeling.

Tier
2
PRZM/
EXAMS
modeling
was
performed
to
estimate
drinking
water
concentrations
for
surface
water
for
novaluron
per
se.
The
scenarios
were
selected
to
provide
high­
end
drinking
water
concentrations
for
each
crop
and
represent
the
geographic
locations
where
the
specific
crops
are
grown
in
large
quantities.

The
most­
conservative
estimates
were
obtained
for
airblast
applications
to
Pennsylvania
apples
at
the
maximum
annual
application
rate
of
0.96
lb
a.
i./
acre,
applied
three
times
at
0.32
lb
a.
i./
acre
with
an
interval
between
applications
of
ten
days.

For
surface
water,
the
1­
in­
10
year
annual
mean
EDWC
for
the
parent
novaluron
is
1.8
:
g/
L
(
ppb).

A
Tier
I
drinking
water
analysis
was
performed
for
the
chlorophenyl
urea
and
chloroaniline
degradates.
The
FIRST
model
was
used
to
obtain
surface
water
estimates.
As
a
conservative
assumption,
the
model
assumed
chlorophenyl
urea
was
directly
applied,
i.
e.,
as
granular,
to
the
field,
assuming
no
spray
drift
and
no
foliar
interception.
The
FIRST
model
estimates
a
peak
and
an
annual
average
value
based
on
the
Index
Reservoir
scenario.
Page
18
of
24
For
surface
water,
the
annual
average
EDWC
for
chlorophenyl
urea
is
0.86
:
g/
L
(
ppb)
and
the
annual
average
EDWC
for
chloroaniline
is
2.6
:
g/
L
(
ppb).
Both
of
these
estimates
are
based
upon
the
maximum
application
rate
in
apples.

For
groundwater,
the
SCI­
GROW
model
was
used
to
predict
a
groundwater
concentration
for
novaluron
at
the
annual
application
rate
of
0.96
lb
a.
i./
acre
(
i.
e.,
three
applications
of
0.32
lb
a.
i./
acre).
The
estimate
for
the
parent
novaluron
is
5.5
x
10­
3
:
g/
L
in
drinking
water
from
shallow
ground
water
sources.
For
the
chlorophenyl
urea
degradate,
the
predicted
ground
water
concentration
is
4.5
x
10­
3
:
g/
L,
and
for
the
chloroaniline
degradate
the
concentration
is
9.0
x
10­
3
:
g/
L.
These
concentrations
were
estimated
with
the
same
assumptions
used
for
surface
water
modeling,
and
may
be
considered
as
both
the
peak
and
annual
average
upper
bound
exposures.

These
EDWC
values
are
meant
to
represent
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
and
groundwater
based
upon
existing
and
proposed
uses.
Of
the
three
EDWC
values,
chronic
estimates
for
the
terminal
metabolite,
chloroaniline
are
the
highest
(
100%
conversion
from
parent
to
aniline
was
assumed).
This
is
consistent
with
the
expected
degradation
pattern
for
novaluron.
Therefore,
the
EDWC
value
for
the
chloroaniline
degradate
(
2.6
ppb)
was
used
to
assess
chronic
aggregate
risk.

4.4
Dietary­
Exposure
Analysis
A
chronic
dietary
risk
assessment
was
conducted
using
the
DEEM­
FCID
 
(
ver.
2.03)
model
which
uses
food
consumption
data
from
the
USDA's
CSFII
from
1994­
1996
and
1998.
An
acute
dietary
assessment
was
not
conducted
for
novaluron
because
an
endpoint
of
concern
attributable
to
a
single
dose
was
not
identified.
A
cancer
dietary
assessment
was
not
conducted
because
novaluron
was
classified
as
"
not
likely
to
be
carcinogenic
to
humans."

The
current
chronic
dietary
assessment
is
an
update
of
the
previous
dietary
assessment
conducted
in
2004
(
i.
e.,
the
current
commodities
associated
with
this
petition
were
added
at
the
HEDrecommended
tolerance
level
to
the
last
dietary
assessment.)
Furthermore,
drinking
water
was
incorporated
directly
in
the
dietary
assessment
using
the
average
annual
concentration.
In
the
last
dietary
assessment,
the
chronic
analysis
assumed
100%
crop
treated
for
all
commodities;
incorporated
average
field
trial
residues;
empirical
processing
factors
for
apple
juice
(
translated
to
pear
juice);
and
DEEM
 
(
ver
7.76)
default
processing
factors
for
the
remaining
processed
commodities.
Furthermore,
ARs
were
calculated
for
meat
and
milk
commodities
and
recommended
tolerances
were
used
for
poultry
commodities
(
partially
refined,
Tier
2
analysis).
The
resulting
chronic
dietary
risk
estimate
(
food
+
water)
was
less
than
HED's
levels
of
concern
(<
100%
cPAD;
see
Table
7).
Page
19
of
24
Table
7.
Summary
of
Dietary
Exposure
and
Risk
for
Novaluron.

Population
Subgroup
Chronic
Dietary
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.002158
20
All
Infants
(<
1
year
old)
0.003662
33
Children
1­
2
years
old
0.007778
71
Children
3­
5
years
old
0.005948
54
Children
6­
12
years
old
0.003577
33
Youth
13­
19
years
old
0.001866
17
Females
13­
49
years
old
0.001418
13
Adults
20­
49
years
old
0.001516
14
Adults
50+
years
old
0.001348
12
4.5
Residential
Exposure
and
Risk
Pathway
All
uses
for
novaluron,
either
proposed
or
existing,
are
agricultural
or
commercial
in
nature.
No
residential
uses
are
proposed,
nor
are
any
of
the
uses
expected
to
result
in
recreational
exposure.
Therefore,
a
residential
exposure
assessment
was
not
performed
for
this
action.

5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
Including
all
existing
and
proposed
uses,
human­
health
risk
assessments
have
been
conducted
for
the
following
exposure
scenario:
chronic
dietary
exposures
(
food
+
water
only).
The
chronic
dietary
exposure
and
risk
estimate
is
below
HED's
level
of
concern.
An
acute
dietary
assessment
was
not
conducted
for
novaluron
because
an
endpoint
of
concern
attributable
to
a
single
dose
was
not
identified.
A
cancer
dietary
assessment
was
not
conducted
because
novaluron
was
classified
as
"
not
likely
to
be
carcinogenic
to
humans."

Because
there
are
no
uses
of
novaluron
that
could
result
in
residential
exposures,
this
aggregate
risk
assessment
takes
into
consideration
dietary
food
+
water
exposure
only;
therefore,
the
chronic
aggregate
estimates
would
be
the
same
as
the
chronic
dietary
exposure
results
shown
in
Table
7.
Page
20
of
24
6.0
CUMULATIVE
RISK
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
as
to
novaluron
and
any
other
substances
and
novaluron
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
novaluron
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/.

7.0
OCCUPATIONAL
EXPOSURE
Reference:
occupational
and
residential
exposure/
risk
assessment
­
Memo,
M.
Clock­
Rust.
DP#
315780.

Occupational
exposure
and
risks
were
assessed
based
on
the
proposed
uses
on
Brassica.
Aerial
and
ground
application
of
liquids
are
the
proposed
methods
of
application.

An
appropriate
endpoint
for
quantification
of
short­
term
dermal
risk
assessment
was
not
identified
by
HIARC
since
no
adverse
effects
were
observed
at
the
limit
dose
in
a
21­
day
dermal
toxicity
study
in
rats,
and
there
were
no
developmental
toxicity
concerns
at
the
limit­
dose.
Therefore,
a
corresponding
short­
term
dermal
risk
assessment
for
this
duration
is
not
required.
For
handlers,
short­
and
intermediate­
term
inhalation
risk
was
assessed,
as
was
intermediate­
term
dermal
risk.
For
post­
application
workers,
intermediate­
term
dermal
risk
was
assessed
(
post­
application
inhalation
exposure
is
considered
to
be
negligible).

7.1
Occupational
Handler
Based
on
the
proposed
use
patterns,
HED
expects
the
most
highly­
exposed
occupational
pesticide
handlers
are
likely
to
be:

1)
mixer­
loaders
using
open­
pour
loading
of
an
EC
(
liquid);
2)
applicators
using
open­
cab
groundboom
equipment;
3)
applicators
using
open­
cab
air­
blast
equipment.

Aerial
applicators
were
not
assessed
since
exposure
data
indicate
they
are
exposed
to
far
less
pesticide
residue
than
applicators
using
open­
cab
ground
equipment
(
airblast
or
groundboom).

For
some
of
the
application
methods,
the
same
individual
might
perform
multiple
activities.
The
HED
Science
Advisory
Council
for
Exposure
(
ExpoSAC)
draft
SOP
(
29­
MAR­
2000)
directs
that
although
the
same
individual
may
perform
all
tasks
in
some
cases,
they
shall
be
assessed
separately.
Page
21
of
24
The
available
exposure
data
for
combined
mixer/
loader/
applicator
scenarios
are
limited
in
comparison
to
the
data
available
for
monitoring
of
these
two
activities
separately.
These
exposure
scenarios
are
outlined
in
the
Pesticide
Handler
Exposure
Database
(
PHED)
Surrogate
Exposure
Guide
(
AUG­
1998).
HED
has
adopted
a
methodology
to
present
the
exposure
and
risk
estimates
separately
for
the
job
functions
in
some
scenarios
and
to
present
them
as
combined
in
other
cases.
Most
exposure
scenarios
for
hand­
held
equipment
(
such
as
hand
wands,
backpack
sprayers,
and
push­
type
granular
spreaders)
are
assessed
as
a
combined
job
function.
With
these
types
of
hand
held
operations,
all
handling
activities
are
assumed
to
be
conducted
by
the
same
individual.
The
available
monitoring
data
support
this
and
HED
presents
them
in
this
way.
Conversely,
for
equipment
types
such
as
fixed­
wing
aircraft,
groundboom
tractors,
or
air­
blast
sprayers,
the
applicator
exposures
are
assessed
and
presented
separately
from
those
of
the
mixers
and
loaders.
By
separating
the
two
job
functions,
HED
determines
the
most
appropriate
levels
of
personal
protective
equipment
(
PPE)
for
each
aspect
of
the
job
without
requiring
an
applicator
to
wear
unnecessary
PPE
that
might
be
required
for
a
mixer/
loader
(
i.
e.,
chemical
resistant
gloves
may
only
be
necessary
during
the
pouring
of
a
liquid
formulation).

No
chemical­
specific
data
were
available
with
which
to
assess
potential
exposure
to
pesticide
handlers.
There
are
three
basic
risk
mitigation
approaches
considered
appropriate
for
controlling
occupational
exposures.
These
include
administrative
controls,
the
use
of
PPE,
and
the
use
of
engineering
controls.
Occupational
handler
exposure
assessments
were
completed
by
HED
using
baseline,
PPE,
and
engineering
controls.
(
Note:
Administrative
controls
available
generally
involve
altering
application
rates
for
handler
exposure
scenarios.
These
are
typically
not
utilized
for
completing
handler
exposure
assessments.)
The
baseline
clothing/
PPE
level
scenario
for
occupational
exposure
scenarios
is
generally
an
individual
wearing
long
pants,
a
long­
sleeved
shirt,
no
chemical­
resistant
gloves,
and
no
respirator.
The
first
level
of
mitigation
generally
applied
is
PPE.
As
reflected
in
the
calculations
included
herein,
PPE
may
involve
the
use
of
an
additional
layer
of
clothing,
chemical­
resistant
gloves,
and
a
respirator.
The
next
level
of
mitigation
considered
in
the
risk
assessment
process
is
the
use
of
appropriate
engineering
controls
which,
by
design,
attempt
to
eliminate
the
possibility
of
human
exposure.
Examples
of
commonly
used
engineering
controls
include
closed
tractor
cabs,
closed
mixing/
loading/
transfer
systems,
and
water­
soluble
packets.

Aerial
application
results
in
the
highest
occupational
exposure
estimates
for
mixer/
loaders
due
to
the
assumption
of
a
larger
area
treated
(
1200
acres).

For
a
summary
of
estimated
exposures
and
risks,
see
Table
8
below.
Page
22
of
24
Table
8.
Estimated
Handler
Exposure
and
Risk
from
the
Use
of
Novaluron
on
Head
and
Stem
Brassica.

Unit
Exposure1
mg
a.
i./
lb
handled
Application
Rate2
Units
Treated3
Per
Day
Average
Daily
Dose4
mg
a.
i./
kg
bw/
day
MOE5
ST
Inhal.
IT
Combined
Mixer/
Loader
­
Liquid
­
Open
Pour
­
Supporting
Aerial
Operations
for
Head
and
Stem
Brassica
Dermal:
SLNG
2.9
HC
SLWG
0.023
HC
Inhal
0.0012
HC
0.078
lb
a.
i./
A
1200
A
Dermal:
SLNG
0.39
SLWG
0.0031
Inhal
0.0016
2,700
NG
11
WG
930
Applicator
­
Groundboom
­
Open
Cab
for
Head
and
Stem
Brassica
Dermal:
SLNG
0.014
HC
SLWG
0.014
MC
Inhal
0.00074
HC
0.078
lb
a.
i./
A
200
A
Dermal:
SLNG/
WG
0.00031
Inhal
0.00016
2,700
NG/
WG
9,300
1.
Unit
Exposures
are
taken
from
"
PHED
SURROGATE
EXPOSURE
GUIDE",
Estimates
of
Worker
Exposure
from
PHED
Version
1.1,
August
1998.
Inhalation.
Unit
Exposures
=
mg
a.
i./
pound
of
active
ingredient
handled.
Data
Confidence:
HC
=
High
Confidence.
2.
Applic.
Rate.
=
Taken
from
proposed
RimOn
®
labels
for
10
%
EC
and
7.5%
WG.
3.
Units
Treated
are
taken
from
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture";
SOP
No.
9.1.
ExpoSAC;
Revised
5
July
2000;
4.
Average
Daily
Dose
(
ADD)
=
Unit
Exposure
*
Applic.
Rate
*
Units
Treated
*
absorption
factor
÷
Body
Weight
(
70
kg).
(
Assumes
10
%
dermal
absorption
and
100
%
inhalation
absorption.)
5.
MOE
=
NOAEL
÷
ADD.
No
short­
term
dermal
endpoint
was
identified
therefore
only
short­
term
inhalation
risk
is
presented
(
NOAEL
=
4.38
mg
a.
i./
kg
bw/
day).
The
intermediate­
term
dermal
and
inhalation
endpoints
are
the
same
(
NOAELs
=
4.38
mg
a.
i./
kg
bw/
day
respectively)
and
are
identified
from
the
same
study.
Therefore,
dermal
exposure
is
summed
with
inhalation
exposure
and
risk
is
presented
for
"
baseline"
work
clothing
and
NO
gloves
(
NG)
as
well
as
"
baseline"
work
clothing
WITH
the
use
of
protective
gloves
(
WG).

All
occupational
risk
estimates
are
below
HED's
level
of
concern
(
MOE>
100)
provided
workers
wear
protective
gloves
when
handling
novaluron.

7.2
Occupational
Postapplication
There
is
a
potential
for
post­
application
exposure
to
workers
from
pesticides
during
the
course
of
typical
agricultural
activities.

The
HIARC
determined
that
there
were
no
signs
of
systemic
toxicity
at
the
limit
dose
of
1,000
mg/
kg/
day
in
a
4­
week
dermal
toxicity
study
in
rats.
As
a
result,
HIARC
did
not
identify
an
endpoint
for
the
quantification
of
short­
term
dermal
risk
assessment,
and
a
corresponding
risk
assessment
for
this
duration
is
not
required.
Dermal
postapplication
exposure
over
the
intermediate­
term
duration
(
more
than
30
consecutive
days)
is
not
typically
expected
to
occur
based
on
the
use
pattern
(
7­
14
day
application
interval).

However,
for
the
last
risk
assessment
(
Memo,
M.
Clock­
Rust,
et
al.,
25­
MAR­
2004;
DP#
295824),
HED's
Risk
Assessment
Review
Committee
(
RARC)
recommended
that
postapplication
exposure
be
assessed
for
the
intermediate­
term
duration
as
a
conservative
measure.
Likewise,
for
the
current
action,
intermediate­
term
post­
application
was
assessed
using
Page
23
of
24
conservative
assumptions
for
the
proposed
uses.

HED
in
conjunction
with
the
Agricultural
Re­
entry
Task
Force
(
ARTF)
has
identified
a
number
of
post­
application
agricultural
activities
that
may
occur.
HED
has
also
identified
TCs
(
expressed
as
cm
²
/
hr)
relative
to
the
various
activities.
To
make
a
conservative
estimate
of
post­
application
exposure
based
on
the
proposed
crop
uses,
HED
chose
hand
harvesting
Brassica
with
a
TC
of
5,000
cm2/
hr
(
central
value
from
ARF012­
TCs
ranging
from
2862
to
7584
cm2/
hr).
Lacking
compound­
specific
data,
HED
assumed
20%
of
the
application
rate
is
available
as
foliar
dislodgeable
residue
on
day
zero
after
application.
This
and
the
TC
estimate
for
irrigation
are
adapted
from
the
ExpoSAC
SOP
No.
003
(
07­
MAY­
1998
­
Revised
07­
AUG­
2000).
The
following
convention
may
be
used
to
estimate
post­
application
exposure.

Surrogate
Dislodgeable
Foliar
Residue
(
DFR):
DFR
=
application
rate
*
20%
available
as
dislodgeable
residue
*
(
1­
D)
t
*
4.54
x
108
µ
g/
lb
*
2.47
x
10­
8
A/
cm2
and,

Average
Daily
Dose
(
ADD)
=
DFR
µ
g/
cm2
*
TC
cm2/
hr
*
hr/
day
*
0.001
mg/
µ
g
*
1/
70
kg
bw
therefore,
0.078
lb
a.
i./
A
*
0.20
*
(
1­
0)
0
*
4.54
x
108
µ
g/
lb
*
2.47
x10­
8
A/
cm
²
=
0.18
µ
g/
cm2
 
0.18
µ
g/
cm2
*
5,000
cm2/
hr
*
8
hr/
day
*
0.001
mg/
µ
g
*
0.10
dermal
absorption
*
1/
70
kg
bw
=
0.010
mg/
kg
bw/
day
Since
MOE
=
NOAEL
÷
ADD
then
4.38
mg/
kg
bw/
day
÷
0.010
mg/
kg
bw/
day
=
440
A
MOE
of
100
is
adequate
to
protect
agricultural
workers
from
post­
application
exposures
to
novaluron.
The
estimated
MOE
is
based
upon
conservative
assumptions
and
is
>
100;
therefore,
estimated
risks
from
post­
application
exposures
do
not
exceed
HED's
level
of
concern.

7.3
Incident
Data
OPP's
Incident
Data
System
(
IDS)
(
29­
DEC­
2003)
indicates
"
no
incident
data"
are
recorded
for
novaluron.
Page
24
of
24
8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
8.1
Toxicology
°
The
HED
HIARC
requested
a
28­
day
inhalation
toxicity
study
as
a
condition
of
registration.
However,
based
on
the
low
volatility
and
low
inhalation
toxicity
(
Category
IV)
of
novaluron
and
inhalation
MOEs
>
1000
for
the
proposed
uses
in
this
risk
assessment,
novaluron
qualifies
for
a
waiver
of
the
28­
day
inhalation
toxicity
study
for
the
proposed
uses
[
HED
SOP
2002.01:
Guidance:
Waiver
Criteria
for
Multiple­
Exposure
Inhalation
Toxicity
Studies,
15­
AUG­
2002].
The
requirement
for
the
28­
day
inhalation
toxicity
study
is
waived
for
this
action
only.
If
in
the
future,
requests
for
new
uses
or
formulations
are
submitted
that
may
result
in
a
significant
change
in
either
the
toxicity
profile
or
exposure
scenarios,
HED
will
reconsider
this
data
requirement.

8.2
Residue
Chemistry
°
Revised
Section
B.
°
Revised
Section
F.
°
Radiovalidation
of
the
GC/
ECD
plant
analytical
method,
using
radiolabeled
samples
from
the
metabolism
studies,
in
order
to
determine
whether
the
method
adequately
extract
aged
(
weathered)
residues
of
novaluron.
°
An
interference
study
to
determine
whether
other
pesticides
registered
on
the
same
commodities
interfere
with
the
determination
of
novaluron;
an
interference
study
may
be
waived
if
a
specific
single
analyte
confirmatory
method
is
submitted.

8.3
Occupational/
Residential
Exposure
°
None.

cc:
S.
Levy
(
RAB1),
P.
Terse
(
RAB1),
M.
Clock­
Rust
(
RAB1)
RDI:
RAB1
Branch
(
02­
NOV­
2005),
P.
V.
Shah
(
03­
NOV­
2005)
S.
Levy:
806T:
CM#
2:
(
703)
305­
0783:
7509C:
RAB1