1
of
52
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
7/
20/
06
SUBJECT:
Azoxystrobin.
Human
Health
Risk
Assessment
for
New
Uses
on
Foliage
of
Legume
Vegetables,
Group
7;
Fruiting
Vegetables,
Group
8
(
Except
Tomato);
Pea
and
Bean,
Succulent
and
Dried
Shelled
(
Except
Soybeans),
Subgroups
6B
and
6C;
Nongrass
Animal
Feeds,
Group
18;
and
Citrus;
and
Section
18
Requests
for
Groups
6
and
7
to
Control
Soybean
Rust.

Petition
#
5E6916
05FL11
05TN11
Chemical
#:
128810
DP
Num:
317291
317331
317333
Class:
Fungicide
40
CFR:
§
180.507
Trade
Name:
Amistar
 
,
Quadris
®
Flowable,
Abound
®
Fungicide,
Heritage
®
Fungicide,
Quilt
 
Fungicide
EPA
Reg.
#:
100­
1164,
100­
1098,
10182­
415,
100­
1093,
110­
1178
FROM:
W.
Cutchin,
Chemist
Alternative
Risk
Integration
Assessment
Team
(
ARIA)
Registration
Division
(
7505P)

THRU:
B.
O'Keefe,
Branch
Senior
Scientist
Registration
Action
Branch
3
Health
Effects
Division
(
7509P)

TO:
D.
Rosenblatt/
B.
Madden
PM­
05
Registration
Division
(
7505P)
2
of
52
1.0
EXECUTIVE
SUMMARY.................................................................................................
3
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION.............................
11
3.0
HAZARD
CHARACTERIZATION
...............................................................................
13
3.1
Hazard
Profile
..............................................................................................................
13
3.2
FQPA
Considerations
..................................................................................................
13
3.3
Dose­
Response
Assessment
..........................................................................................
14
3.4
Endocrine
Disruption...................................................................................................
16
4.0
EXPOSURE
ASSESSMENT...........................................................................................
16
4.1
Summary
of
Proposed
Uses
..........................................................................................
16
4.2
Dietary
Exposure/
Risk
Pathway..................................................................................
22
4.2.1
Residue
Profile.......................................................................................................
22
4.2.2
Dietary
Analysis.....................................................................................................
28
4.2.2.1
Acute
Dietary
..................................................................................................
28
4.2.2.2
Chronic
Dietary
..............................................................................................
30
4.2.2.3
Cancer
Dietary................................................................................................
30
4.3
Water
Exposure/
Risk
Pathway....................................................................................
30
4.4
Residential
Exposure/
Risk
Pathway............................................................................
31
4.4.1
Home
Uses..............................................................................................................
32
4.4.2
Residential
Handler
Exposure
and
Risk...............................................................
32
4.4.3
Residential
Postapplication
Exposure
and
Risk...................................................
35
4.4.4
Recreational
Postapplication
Exposure
and
Risk
................................................
39
4.4.5
Off
Target
Non­
Occupational
Exposure...............................................................
39
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION.............
39
5.1
Acute
Aggregate
Risk...................................................................................................
39
5.2
Short­
Term
Aggregate
Risk.........................................................................................
39
5.3
Intermediate­
Term
Aggregate
Risk.............................................................................
41
5.4
Chronic
Aggregate
Risk...............................................................................................
41
5.5
Cancer
Aggregate
Risk
................................................................................................
42
6.0
CUMULATIVE
RISK
.....................................................................................................
42
7.0
OCCUPATIONAL
EXPOSURE.....................................................................................
42
7.1
Occupational
Handler
..................................................................................................
42
7.2
Occupational
Postapplication
Exposure
and
Risk
.....................................................
51
8.0
DATA
NEEDS..................................................................................................................
51
8.1
Toxicology.....................................................................................................................
51
8.2
Residue
Chemistry
.......................................................................................................
52
8.3
Occupational/
Residential................................................................................................
52
References
................................................................................................................................
52
3
of
52
1.0
EXECUTIVE
SUMMARY
Background
In
petition
PP#
5E6916,
the
Interregional
Research
Project
No.
4
(
IR­
4)
is
proposing
the
use
of
azoxystrobin
on
citrus;
foliage
of
legume
vegetables,
Group
7;
vegetables,
fruiting,
Group
8
(
except
tomato);
pea
and
bean,
succulent
and
dried
(
except
soybean),
Subgroups
6B
and
6C;
and
nongrass
animal
feeds,
Group
18.
In
05FL11
and
05TN11,
the
states
of
Florida
and
Tennessee
are
requesting
quarantine
exemption
Section
18
registrations
for
the
use
of
multiple
formulations,
one
of
which
includes
azoxystrobin,
for
the
treatment
of
soybean
rust
on
specialty
legumes
in
Group
6
(
excluding
soybeans)
and
Group
7.
Assessments
of
human
exposures
and
risks
were
conducted
for
acute
and
chronic
dietary
risk;
exposure
and
risk
to
azoxystrobin
residues
in
water;
residential
exposure
and
risk;
aggregate
risk;
and
exposure
and
risk
to
workers.

Azoxystrobin
is
a
broad
spectrum
fungicide
for
control
of
many
plant
diseases.
It
has
the
same
biochemical
mode
of
action
as
the
naturally
occurring
strobilurins
and
is
structurally
related
to
them.
Azoxystrobin
is
a
 ­
methoxyacrylate.
It
is
in
the
same
chemical
class
as
trifloxystrobin.
Azoxystrobin
acts
by
inhibiting
electron
transport.
There
are
numerous
tolerances
established
for
azoxystrobin
ranging
from
0.02
ppm
on
cottonseed
to
the
Herb
Subgroup
19A,
dried,
except
chive
at
260
ppm.

Proposed
Uses
For
petition
PP#
5E6916,
the
proposed
uses
are
for
four
applications
of
azoxystrobin
at
0.1­
0.25
lb
ai/
A,
up
to
1.0
lb
ai/
A/
season
at
0­
day
preharvest
interval
(
PHI)
on
the
foliage
of
legume
vegetables,
Group
7;
vegetables,
fruiting,
Group
8
(
except
tomato);
pea
and
bean,
succulent
and
dried
(
except
soybean),
Subgroups
6B
and
6C;
and
nongrass
animal
feeds,
Group
18.
The
petitioner
has
also
proposed
a
postharvest
use
on
citrus
for
two
applications
using
water,
wax/
oil
emulsion,
or
aqueous
dilution
of
wax/
oil
emulsion
at
0.53­
1.06
lb
ai/
250,000
lbs
of
fruit
up
to
1.5
lb
ai/
250,000
lbs
of
fruit
following
the
previously
established
use
for
four
applications
at
0.20­
0.25
lb
ai/
A,
up
to
1
lb
ai/
A/
season
at
0­
day
PHI.

For
05FL11
and
05TN11,
axozystrobin
as
formulated
in
Quilt
 
Fungicide
(
EPA
REG.
No.
110­
1178)
will
be
applied
twice
at
0.014
lb
ai/
A,
up
to
0.028
lb
ai/
A/
season
with
a
0­
day
PHI
on
Group
6
(
except
soybeans)
and
Group
7.
The
use
is
requested
in
response
to
the
threat
of
soybean
rust
on
specialty
legumes.

Toxicology
and
Dose­
Response
The
toxicology
database
is
complete
and
there
are
no
data
gaps.
Endpoints
were
chosen
for
acute
and
chronic
dietary,
short­
and
intermediate­
term
incidental
oral
and
inhalation
but
not
for
short­,
intermediate­
or
long­
term
dermal
exposure
assessment.
No
short­,
intermediate­
or
long­
term
dermal
endpoints
were
chosen
because
no
dermal
or
systemic
toxicity
was
seen
at
the
limit
dose
(
1000
mg/
kg/
day)
in
a
repeated­
dose
21­
day
dermal
toxicity
study
in
rats.
4
of
52
The
acute
dietary
reference
dose
(
RfD)
is
based
on
the
results
of
an
acute
neurotoxicity
study
in
which
rats
had
diarrhea
at
the
lowest­
observed
adverse
effects
level
(
LOAEL)
of
200
mg/
kg/
day.
The
acute
RfD
and
the
acute
population­
adjusted
dose
(
aPAD)
are
0.7
mg/
kg/
day
(
uncertainty
factor
or
UF=
300).
The
chronic
dietary
RfD
is
based
on
the
results
of
a
combined
chronic
toxicity/
carcinogenicity
study
in
which
male
rats
had
reduced
body
weights,
food
consumption
and
food
efficiency,
and
bile
duct
lesions
at
the
LOAEL
of
34
mg/
kg/
day
and
the
LOAEL
for
females
is
117
mg/
kg/
day
based
on
reduced
body
weights.
The
no­
observed
adverse
effects
level
(
NOAEL)
in
males
is
18.2
mg/
kg/
day
and
the
NOAEL
for
females
is
22.3
mg/
kg/
day.
The
chronic
RfD
and
the
chronic
population­
adjusted
dose
(
cPAD)
are
0.18
mg/
kg/
day
(
UF=
100).

The
short­
term
incidental
oral
NOAEL
is
from
a
prenatal
developmental
oral
study
in
rats,
based
on
increased
maternal
diarrhea
and
other
effects
observed
at
the
LOAEL
of
100
mg/
kg/
day).
The
NOAEL
is
25
mg/
kg/
day
(
UF=
100).
The
intermediate­
term
incidental
oral
NOAEL
is
from
a
90­
day
feeding
study
in
rats,
based
on
decreased
body
weight
gain
and
clinical
signs
observed
at
the
LOAEL
of
211/
223
mg/
kg/
day
for
males
and
females,
respectively.
The
NOAEL
is
21
mg/
kg/
day
(
UF=
100).
No
short­,
intermediate­
or
long­
term
dermal
endpoints
were
chosen
because
no
dermal
or
systemic
toxicity
was
seen
at
the
limit
dose
(
1000
mg/
kg/
day)
in
a
repeated­
dose
21­
day
dermal
toxicity
study
in
rats.
The
short­
term
inhalation
NOAEL
is
the
same
as
that
selected
for
short­
term
incidental
oral
exposure.
Similarly,
the
intermediate­
term
inhalation
NOAEL
is
the
same
as
that
selected
for
intermediate­
term
incidental
oral.
A
longterm
inhalation
endpoint
was
not
chosen
because
the
risk
assessment
is
not
applicable
to
the
current
use
pattern
for
azoxystrobin.

The
FQPA
Safety
Factor
Committee
recommended
that
the
10­
fold
safety
factor
for
increased
susceptibility
of
infants
and
children
be
removed
(
i.
e.,
reduced
to
1x)
in
assessing
the
risk
posed
by
this
chemical.

There
is
no
evidence
for
mutagenicity
or
carcinogenicity.
Azoxystrobin
has
been
classified
as
"
not
likely
to
be
carcinogenic
in
humans"
by
Hazard
Identification
Assessment
Review
Committee
(
HIARC,
11/
7/
96);
therefore,
no
carcinogenic
risk
analyses
were
performed.

Dietary
Risk
from
Drinking
Water
Sources
Although
moderately
persistent
in
soils
and
stable
to
hydrolysis,
the
likelihood
of
azoxystrobin
moving
into
ground
and
surface
water
is
low
due
to
high
soil/
water
partitioning
coefficients
and
low
single
application
rates.
The
HED
Metabolism
Assessment
Review
Committee
(
MARC)
determined
that
the
residue
of
concern
in
water
is
azoxystrobin
only,
because
the
parent
compound
is
the
most
likely
residue
to
be
found
in
surface
water.

Monitoring
data
are
not
available
to
perform
a
quantitative
drinking
water
risk
assessment
for
azoxystrobin
at
this
time.
EFED
provided
estimated
environmental
concentrations
(
EDWCs)
for
azoxystrobin
based
upon
the
crop
with
the
highest
application
rate
(
turf).
Tier
1
surface
and
ground
water
EECs
were
generated
using
EFED's
FIFRA
Index
Reservoir
Screening
Tool
(
FIRST)
and
Screening
Concentration
in
Ground
Water
(
SCI­
GROW)
5
of
52
models,
respectively.
As
the
use
of
azoxystrobin
on
turf
has
the
highest
yearly
application
rate
(
5
lb/
A/
year),
this
application
rate
was
used
in
the
FIRST
and
SCI­
GROW
models
to
estimate
the
concentrations
of
this
chemical
in
surface
and
ground
water,
respectively.
Should
the
yearly
application
rate
on
non­
cropland
change,
or
should
a
use
of
azoxystrobin
with
a
higher
use
rate
be
added,
EFED
may
have
to
revise
the
EDWCs
accordingly.

Based
on
the
SCI­
GROW
screening
model
and
the
highest
use
rate
(
turf
use,
9
applications
per
year,
10­
day
interval,
and
0.55
lb
ai/
A/
application),
the
upper­
bound
concentration
of
azoxystrobin
in
ground
water
was
estimated
at
3.1
ppb.
This
value
can
be
used
for
both
acute
and
chronic
risk
assessments.
This
value
represents
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
ground
water
which
result
from
the
use
of
azoxystrobin
on
turf.
Based
on
the
FIRST
Tier
1
modeling
results,
azoxystrobin
EECs
in
surface
water
are
not
likely
to
exceed
170
ppb
for
the
acute
(
peak)
concentration
or
33
ppb
for
the
chronic
(
annual
average)
concentration.
These
values
represent
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
which
result
from
the
use
of
azoxystrobin
on
turf.

Dietary
Risk
Residue
Chemistry
Adequate
plant
metabolism
studies
on
azoxystrobin
have
been
previously
conducted
using
grapes,
peanuts,
and
wheat.
Azoxystrobin
undergoes
photochemical
isomerization
to
produce
the
Z­
isomer
and
is
extensively
metabolized
in
plants.
Adequate
livestock
metabolism
studies
for
azoxystrobin
have
also
been
submitted.
The
HED
MARC
has
determined
that
the
residues
of
concern
in/
on
plants
for
the
tolerance
expression
and
risk
assessment
are
azoxystrobin
[
methyl
(
E)­
2­(
2­(
6­(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy)
phenyl)­
3­
methoxyacrylate]
and
the
Z­
isomer
of
azoxystrobin,
[
methyl
(
Z)­
2­(
2­(
6­
(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy)
phenyl)­
3
methoxyacrylate].
The
MARC
also
determined
that
the
residue
of
concern
in/
on
livestock
for
the
tolerance
expression
and
risk
assessment
is
azoxystrobin
only.

Adequate
methodology
is
available
for
enforcement
of
the
established
tolerances
on
plants.
The
gas
chromatography
with
nitrogen
phosphorus
detector
GC/
NPD
method
(
RAM
243/
04)
has
undergone
a
method
validation
by
the
EPA
analytical
laboratory.
EPA
comments
have
been
incorporated
and
the
revised
method
(
designated
RAM
243,
dated
5/
15/
98;
MRID
44595105)
has
been
submitted
to
FDA
for
inclusion
in
the
Pesticide
Analytical
Manual
Volume
II
(
PAM
II)
as
an
enforcement
method.
Adequate
methodology
is
available
for
enforcement
of
the
established
tolerances
on
livestock.
The
GC
method
255/
01
has
been
validated
by
the
EPA
analytical
laboratory
for
the
analysis
of
milk
and
livestock
tissues.
The
EPA
laboratory's
written
report
with
an
EPA
addendum
to
accompany
the
method,
and
the
method,
will
be
submitted
to
FDA
for
inclusion
in
PAM,
Vol.
II.
Citrus
samples
were
analyzed
for
residues
of
azoxystrobin
and
its
Z­
isomer
using
Zeneca
Report
Number
RAM
243/
04,
via
GC/
NPD
with
minor
modifications.
Limit
of
detection
(
LOD)
for
azoxystrobin
and
Z­
isomer
were
established
at
0.0092
ppm
and
0.0065
ppm
in
grapefruit,
0.011
ppm
and
0.0074
ppm
in
orange,
and
0.0077
ppm
and
0.0056
ppm
in
lemon.
Limit
of
quantitation
(
LOQ)
for
azoxystrobin
and
Z­
isomer
were
established
at
0.028
ppm
and
0.020
ppm
in
grapefruit,
0.034
ppm
and
0.022
ppm
in
orange,
and
0.023
ppm
and
0.017
ppm
in
lemon.
Data
pertaining
to
the
multiresidue
methods
testing
of
azoxystrobin
in
conjunction
with
the
grape
tolerance
petition
have
previously
been
submitted.
6
of
52
The
data
indicate
that
azoxystrobin
could
not
be
recovered
through
application
of
the
multiresidue
protocols.
These
data
have
been
forwarded
to
FDA.

No
new
residue
field
trial
data
were
submitted
for
the
foliage
of
legume
vegetables,
Crop
Group
7;
vegetable,
fruiting,
Group
8
(
except
tomato);
pea
and
bean,
succulent
and
dried,
except
soybean,
Subgroups
6B
and
6C;
or
nongrass
animal
feeds,
Group
18.
The
representative
commodities
for
Group
7
are
foliar
portions
of
any
cultivar
of
bean,
field
pea,
and
soybean.
RAB2
previously
stated
that
as
long
as
the
use
pattern
is
similar
and
the
proposed
field
trial
residue
data
supporting
a
tolerance
for
Group
4
are
submitted
and
deemed
adequate,
it
will
be
appropriate
to
request
a
tolerance
for
Group
7
at
the
same
level
as
Group
4.
The
requirements
set
forth
by
RAB2
for
the
establishment
of
an
azoxystrobin
tolerance
on
the
foliage
of
legume
vegetables,
Group
7
have
been
satisfied.
TRB
recommends
for
the
establishment
of
a
tolerance
at
30.0
ppm
for
the
residues
of
azoxystrobin
on
vegetables,
foliage
of
legume,
Group
7.
Since
the
proposed
tolerance
on
Group
7
will
include
a
soybean
hay
and
forage,
the
existing
tolerances
on
those
commodities
should
be
removed.

There
are
tolerances
established
for
members
of
Group
8:
peppers,
okra,
and
eggplant
at
2.0
ppm,
and
tomato
at
0.2
ppm
(
CFR
§
180.507).
Although
all
the
existing
residue
data
on
the
Group
8
representative
commodities
were
determined
to
be
sufficient
to
establish
a
crop
group
tolerance,
risk
cup
issues
at
the
time
precluded
increasing
the
tomato
tolerance
and
separate
tolerances
were
requested
on
okra
and
eggplant.
Since
the
existing
data
were
determined
to
be
adequate
for
a
crop
group
tolerance,
there
is
sufficient
data
to
support
the
petition
for
the
requested
subgroup.
However,
the
commodity
definition
presented
by
the
petitioner
is
incorrect.
A
new
Section
F
should
be
submitted
requesting
a
tolerance
for
the
residues
of
azoxystrobin
at
2.0
ppm
on
vegetables,
fruiting,
Group
8
(
except
tomato).
The
existing
separate
tolerances
on
pepper,
okra,
and
eggplant
should
be
removed.

The
existing
tolerance
commodity
definitions
are:
pea
and
bean,
dried
shelled,
except
soybean,
subgroup,
except
cowpea,
and
field
pea;
and
pea
and
bean,
succulent
shelled,
subgroup,
except
cowpea.
The
subgroup
tolerances
excluded
cowpea
and
field
pea
because
there
was
no
residue
field
data
for
forage,
hay,
and/
or
silage
as
livestock
feeds.
In
order
to
satisfy
the
data
requirements,
RAB3
previously
indicated
that
residue
data
on
the
representative
crops
of
Group
7
were
required.
However,
as
stated
above,
the
requirements
set
forth
by
RAB2
for
the
establishment
of
an
azoxystrobin
tolerance
on
vegetables,
foliage
of
legume,
Group
7
have
been
satisfied.
Therefore,
no
further
residue
field
trial
data
is
required.
TRB
recommends
for
the
establishment
of
tolerances
at
0.5
ppm
for
the
residues
of
azoxystrobin
on
pea
and
bean,
succulent
shelled,
Subgroup
6B;
and
pea
and
bean,
dried
shelled,
except
soybean,
Subgroup
6C.

IR­
4
requested
that
the
Agency
use
data
supporting
the
tolerances
for
vegetable,
leafy,
except
Brassica,
Group
4
at
30.0
ppm,
Brassica,
leafy
greens,
Subgroup
5B
at
25
ppm,
and
soybean,
hay
at
55.0
ppm
to
support
the
establishment
of
tolerances
for
animal
feed,
nongrass,
Group
18,
forage
at
30.0
ppm
and
animal
feed,
nongrass,
Group
18,
hay
at
55.0
ppm.
ChemSAC
has
determined
that
the
existing
data
cited
by
the
petitioner
is
not
sufficient
to
support
the
requested
tolerance.
TRB
recommends
against
the
proposed
tolerances
on
animal
feed,
nongrass,
Group
18,
forage
and
hay.
However,
TRB
concluded,
based
on
the
existing
use
on
7
of
52
soybeans,
which
has
the
same
use
pattern
as
that
proposed
for
animal
feed,
nongrass,
Group
18,
a
reduced
number
of
residue
field
trials
would
be
appropriate.
Six
residue
field
trials
each
with
the
appropriate
geographic
distribution
on
the
two
representative
crops
for
animal
feed,
nongrass,
Group
18,
alfalfa
and
clover
are
required
to
support
a
proposed
azoxystrobin
tolerance.

There
is
an
existing
use
for
azoxystrobin
on
citrus
fruit
with
an
established
tolerance
of
2.0
ppm.
The
citrus
field
trials
were
conducted
to
demonstrate
the
residues
of
azoxystrobin
in
fruit
which
were
treated
by
simulated
postharvest
applications
following
normal
preharvest
use.
The
petitioner
first
treated
the
fruit
according
to
the
existing
preharvest
use
and
showed
that
quantifiable
residues
were
found
similar
to
those
previously
found
from
the
use.
Those
fruit
were
then
treated
with
azoxystrobin
using
six
different
postharvest
methods.
The
highest
azoxystrobin
residues
were
detected
in
grapefruit,
orange
and
lemon
samples
that
received
preharvest
as
well
as
postharvest
dip
treatments
ranging
from
1.18
to
5.43
ppm,
1.213
4.00
ppm,
and
1.47
to
9.18
ppm,
respectively.
The
results
of
the
residue
chemistry
field
trials
indicate
that
the
residues
of
azoxystrobin
following
both
preharvest
and
postharvest
uses
are
not
likely
to
exceed
the
proposed
tolerance
on
citrus
fruit.

Previous
uses
on
legumes,
except
soybeans,
included
four
applications
of
up
to
0.25
lb
ai/
A
with
a
seasonal
maximum
of
1.0
lb
ai/
A.
Residues
of
azoxystrobin
from
the
established
use
pattern
did
not
exceed
0.5
ppm,
which
is
the
recommended
tolerance
on
pea
and
bean,
succulent
shelled,
Subgroup
6B;
and
pea
and
bean,
dried
shelled,
except
soybean,
Subgroup
6C.
The
requested
Section
18
uses
will
not
exceed
the
established
tolerances;
therefore
TRB
recommends
for
the
requested
use.

There
are
no
processed
commodities
associated
with
the
uses
of
azoxystrobin
on
foliage
of
legume
vegetables,
Group
7;
vegetables,
fruiting,
Group
8
(
except
tomato);
and
pea
and
bean,
succulent
and
dried
shelled,
except
soybean,
Subgroups
6B
and
6C.
The
livestock
feed
items
of
regulatory
interest
for
the
current
action
are
cowpea
seed
at
0.05
ppm,
cowpea
hay
and
forage
at
30.0
ppm;
and
soybean,
forage
and
hay,
for
which
the
tolerance
will
be
raised
to
30
ppm.
Since
the
worst
case
cattle
and
swine
diets
using
existing
and
proposed
tolerances
will
not
exceed
the
level
of
the
ruminant
feeding
study
used
to
establish
the
current
tolerances,
no
increase
in
tolerances
for
ruminant
and
swine
commodities
are
required.
None
of
the
commodities
for
which
tolerances
are
proposed
have
poultry
feed
items
of
regulatory
interest,
therefore
no
change
in
azoxystrobin
poultry
tolerances
is
required.

No
new
processing
studies
were
submitted
for
azoxystrobin
on
citrus
fruit.
Based
on
the
Highest
Average
Field
Trial
(
HAFT)
residue
for
citrus
fruit
of
8.7
ppm
from
the
current
field
trials
and
the
average
concentration
factors
from
the
previously
submitted
processing
studies
of
2.1x
for
pulp,
and
4.6x
for
oil,
the
petitioner's
requests
for
proposed
tolerances
are
adequate.

The
proposed
uses
will
have
no
impact
on
the
established
tolerances
of
animal
commodities.
The
feed
items
associated
with
the
proposed
uses,
citrus
dried
pulp
and
canola
meal,
have
already
been
considered
and
found
to
have
no
effect
on
the
maximum
theoretical
dietary
burden
(
MTDB)
of
azoxystrobin
for
livestock.
The
addition
of
the
only
other
livestock
8
of
52
feed
item
associated
with
these
actions,
sunflower
meal,
will
also
have
no
effect
on
the
MTDB
to
livestock.
Accordingly,
the
current
tolerances
for
animal
commodities
are
adequate.

Adequate
confined
and
field
rotational
crop
studies
are
available
to
support
rotational
crop
restrictions.

Dietary
Exposure
Analysis
The
acute
dietary
exposure
analysis
for
azoxystrobin
is
a
Tier
1
assessment
because
no
additional
data
were
used
to
refine
the
analysis.
One
hundred
percent
of
proposed
and
registered
crops
are
assumed
treated
with
azoxystrobin
(
100%
CT)
and
tolerancelevel
residues
were
used
in
the
analysis.
The
acute
dietary
endpoint
applies
to
all
population
subgroups
including
infants
and
children.
The
highest
estimate
for
acute
drinking
water
exposure,
170
ppb,
was
used
in
the
analysis.
The
dietary
exposure
estimates
for
the
U.
S.
population
at
27%
of
the
aPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
at
74%
of
the
aPAD,
do
not
exceed
HED's
level
of
concern.

The
chronic
dietary
exposure
analysis
for
azoxystrobin
is
a
Tier
2
assessment
using
some
percent
crop
treated
(%
CT)
information
for
selected
crops.
Tolerance­
level
residues
were
used
in
the
analysis.
The
chronic
dietary
endpoint
applies
to
all
population
subgroups
including
infants
and
children.
The
highest
estimate
for
chronic
drinking
water
exposure,
33
ppb,
was
used
in
the
analysis.
The
dietary
exposure
estimate
for
the
U.
S.
population
was
8%
of
the
cPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
was
19%
of
the
cPAD.
Risk
estimates
for
all
population
subgroups
are
below
HED's
level
of
concern
(
100%
of
the
cPAD).

Residential
Risk
Azoxystrobin
is
currently
registered
for
use
on
residential
turfgrass
and
ornamentals,
as
well
as
indoor
surfaces.
Short­
term
exposures
may
occur
during
adult
residential
handling
activities.
HED's
Draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments,
and
Recommended
Revisions
(
ExpoSAC
Policy
Number
12,
revised
2/
22/
01),
were
used
as
the
basis
for
all
residential
handler
exposure
calculations.
Some
of
the
handler
exposure
data
used
in
this
assessment
are
from
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF;
the
risk
manager
is
encouraged
to
pursue
data
compensation
in
the
event
the
registrant
is
not
a
member
of
the
task
force).
Non­
occupational
handler
inhalation
margins
of
exposure
(
MOE)
were
1,700,000
for
mixing,
loading
and
applying
the
WDG
formulation
to
indoor
surfaces,
and
2,700,000
and
230,000
for
mixing,
loading
and
applying
liquid
formulation
to
turf,
for
spot
application
with
a
low­
pressure
handwand
and
for
broadcasting
with
a
garden
hose­
end
sprayer
to
turf,
respectively.
These
MOEs
are
well
above
the
level
of
concern
(
LOC)
for
nonoccupational
handler
scenarios.

Short­
and
intermediate­
term
exposures
may
occur
during
postapplication
activities
for
adults
and
children
(
however,
adult
postapplication
is
not
assessed
because
no
dermal
hazard
was
identified).
Toddlers
may
experience
short­
and
intermediate­
term
exposure
to
azoxystrobin
via
incidental
(
non­
dietary)
ingestion
during
postapplication
activities
on
treated
turf
(
i.
e.,
hand­
tomouth
object­
to­
mouth
[
turfgrass],
and
soil
ingestion)
and
during
postapplication
activities
on
treated
indoor
surfaces
(
i.
e.,
hand­
to­
mouth).
The
postapplication
risk
assessment
is
based
on
9
of
52
generic
assumptions
as
specified
by
the
Recommended
Revisions
to
the
Residential
SOPs
and
recommended
approaches
by
HED's
ExpoSAC.
Postapplication
non­
dietary
ingestion
MOEs
ranged
from
280
to
530,000
for
short­
term
exposure
from
hand­
to­
mouth
activities
on
treated
indoor
surfaces
and
soil
ingestion
on
treated
turf,
respectively.
All
calculated
non­
occupational
postapplication
MOEs
are
greater
than
100
on
the
day
of
application,
and
do
not
exceed
HED's
level
of
concern.

Aggregate
Risk
Acute,
short­
term,
intermediate­
term,
and
chronic
aggregate
risk
estimates
resulting
from
aggregate
exposure
to
azoxystrobin
from
food,
drinking
water,
and
residential
uses
are
below
HED's
level
of
concern.

For
the
acute
aggregate
risk
scenario,
food
and
drinking
water
exposures
were
taken
into
account
in
the
dietary
exposure
assessment.
The
estimated
dietary
exposures
(
food
and
water)
for
the
U.
S.
population
at
27%
of
the
aPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
at
74%
of
the
aPAD
does
not
exceed
HED's
level
of
concern.

For
the
short­
term
aggregate
risk
scenario,
food,
drinking
water
and
residential
exposures
are
taken
into
account.
No
endpoint
has
been
selected
for
short­
term
dermal
exposure
to
azoxystrobin;
therefore,
this
assessment
will
combine
dietary/
incidental
oral
exposure
with
inhalation
exposure.
The
chronic
dietary
exposure
estimate
to
the
U.
S.
population
was
8%
of
the
cPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
was
19%
of
the
cPAD.
The
aggregate
short­
term
MOEs,
combining
food,
drinking
water
and
residential
exposures
ranged
from
200
for
children
1­
2
yrs
old
to
2150
for
females
13­
49
yrs
old.
Risk
estimates
for
all
population
subgroups
are
below
HED's
level
of
concern
(
MOEs
of
100
or
less).

For
the
intermediate­
term
aggregate
risk
scenario,
food,
drinking
water
and
residential
exposures
are
taken
into
account.
No
endpoint
has
been
selected
for
intermediate­
term
dermal
exposure
to
azoxystrobin;
therefore,
this
assessment
will
combine
dietary/
incidental
oral
exposure
with
inhalation
exposure.
An
intermediate­
term
risk
assessment
is
not
required
for
adults
because
intermediate­
term
residential
handler
scenarios
are
not
expected
to
occur.
However,
an
intermediate­
term
risk
assessment
is
required
for
infants
and
children
because
there
is
a
residential
post­
application
oral
exposure
scenario.
The
chronic
dietary
exposure
estimate
to
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
was
19%
of
the
cPAD.
The
aggregate
intermediate­
term
MOE,
combining
food,
drinking
water
and
residential
exposures
for
the
most
highly
exposed
subgroup
was
260
for
children
1­
2
yrs
old.
Risk
estimates
for
all
population
subgroups
are
below
HED's
level
of
concern
(
MOEs
of
100
or
less).

For
the
chronic
aggregate
risk
scenario,
food,
drinking
water,
and
residential
exposures
were
taken
into
account.
In
this
case,
chronic
exposure
in
residential
settings
is
not
expected
and
the
aggregate
chronic
assessment
included
food
and
drinking
water
only.
Since
the
dietary
exposure
assessment
already
includes
the
highest
chronic
exposure
from
the
drinking
water
modeling
data,
no
further
calculations
are
necessary.
The
dietary
exposure
estimate
to
the
U.
S.
population
was
8%
of
the
cPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
was
10
of
52
19%
of
the
cPAD.
Risk
estimates
for
all
population
subgroups
are
below
HED's
level
of
concern
(
100%
of
the
cPAD).
Therefore,
chronic
aggregate
risk
is
below
HED's
level
of
concern.

Occupational
Exposure
and
Risk
No
chemical­
specific
handler
exposure
data
were
submitted
in
support
of
this
Section
3
registration.
It
is
the
policy
of
the
HED
to
use
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1
as
presented
in
PHED
Surrogate
Exposure
Guide
(
8/
98)
to
assess
handler
exposures
for
regulatory
actions
when
chemical­
specific
monitoring
data
are
not
available
(
HED
Science
Advisory
Council
for
Exposure
[
ExpoSAC]
Draft
Policy
#
7,
dated
1/
28/
99).

Occupational
handlers'
inhalation
margins
of
exposure
(
MOEs)
range
from
17,000
for
intermediate­
term
exposure
from
mixing
and
loading
liquid
formulations
for
aerial
application
and
chemigation
to
6,300,000
for
short­
term
mixing,
loading
liquids
for
high
pressure
handwand
application.
These
MOEs
are
well
above
the
level
of
concern
(
LOC)
for
occupational
scenarios,
which
is
an
MOE
of
100
or
below.

Although
occupational
postapplication
dermal
exposure
is
possible
following
treatment
of
use
sites
with
azoxystrobin,
because
no
dermal
endpoints
were
identified
for
this
exposure
potential
(
and
inhalation
exposure
is
expected
to
be
negligible
for
reentry
activities)
a
postapplication
risk
assessment
was
not
conducted.
Nevertheless,
per
the
Worker
Protection
Standard
(
WPS),
a
12­
hour
restricted
entry
interval
(
REI)
is
required
for
chemicals
classified
under
Toxicity
Category
III
or
IV,
which
are
the
Toxicity
Categories
azoxystrobin
is
classified
under
(
Toxicity
Category
III
for
acute
dermal
and
primary
eye
irritation,
and
Toxicity
Category
IV
for
primary
skin
irritation).
Even
though
a
12­
hour
REI
is
the
shortest
waiting
period
permitted
under
the
WPS,
REIs
may
be
further
reduced
from
12
hours
if
certain
criteria
are
met
for
both
the
technical
material
and
the
different
end­
use
products
(
EUPs).
Previously,
HED
determined
that
the
criteria
for
the
technical
material
had
been
met
for
azoxystrobin,
and
RD
had
determined
the
criteria
for
the
EUPs
Abound,
Amistar
and
Heritage
had
been
met
for
those
formulations,
and
therefore,
that
a
4­
hour
REI
is
acceptable
for
those
formulations.
Azoxystrobin
formulation
A12910C
contains
cyproconazole
as
well,
which
does
not
meet
all
the
criteria
for
a
reduced
REI.

Recommendation
for
Tolerances
Provided
a
revised
Section
F
is
received,
the
Agency
recommends
establishing
permanent
tolerances
for
the
combined
residues
of
azoxystrobin,
[
methyl(
E)­
2­(
2­(
6­(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy)
phenyl)
­
3­
methoxyacrylate]
and
the
Z­
isomer
of
azoxystrobin,
[
methyl(
Z)­
2­(
2­(
6­(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy)
phenyl)­
3
methoxyacrylate],
in/
on
the
following
commodities
be
established:
11
of
52
Commodity
Tolerance
(
ppm)

vegetables,
foliage
of
legume,
Group
7
30.0
vegetables,
fruiting,
Group
8
(
except
tomato)
2.0
pea
and
bean,
succulent
shelled,
Subgroup
6B
0.5
pea
and
bean,
dried
shelled,
except
soybean,
Subgroup
6C
0.5
citrus,
dried
pulp
20.0
citrus,
oil
40.0
fruit,
citrus,
Group
10
10.0
TRB
recommends
against
the
requested
tolerance
on
animal
feed,
nongrass,
Group
18
forage
and
hay.
The
residue
chemistry
database
is
not
adequate
to
support
the
requested
use,
and
additional
residue
field
trial
data
is
required.

The
requested
Section
18
uses
on
speciality
legumes
will
not
exceed
the
established
azoxystrobin
tolerances;
therefore
TRB
recommends
for
the
requested
uses.

Note
to
PM:
The
existing
tolerances
on
soybean
hay
and
forage,
pepper,
okra,
and
eggplant
should
be
removed.

The
restricted­
entry
interval
(
REI)
on
the
Quilt
label
is
24
hours,
but
the
REI
is
not
indicated
on
the
Section
18
label
addendum.

2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
Azoxystrobin
is
a
broad
spectrum
fungicide
for
control
of
many
plant
diseases.
It
has
the
same
biochemical
mode
of
action
as
the
naturally
occurring
strobilurins
and
is
structurally
related
to
them.
Azoxystrobin
is
a
 ­
methoxyacrylate.
It
is
in
the
same
chemical
class
as
trifloxystrobin.
Azoxystrobin
acts
by
inhibiting
electron
transport.

TABLE
2.0.1
Test
Compound
Nomenclature
Compound
Chemical
Structure
12
of
52
Common
name
azoxystrobin
Company
experimental
name
ICIA5504
IUPAC
name
methyl
(
E)­
2­{
2­[
6­(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy]
phenyl}­
3­
methoxyacrylate
CAS
name
methyl
(
E)­
2­[[
6­(
2­
cyanophenoxy)­
4­
pyrimidinyl]
oxy]­
 
­
(
methoxymethylene)­
benzeneacetate
CAS
#
131860­
33­
8
End­
use
product/
EP
Amistar
 
(
EPA
Reg.
No.:
100­
1164),
Quadris
®
Flowable
(
EPA
Reg.
No.:
100­
1098),
Abound
®
Fungicide
(
EPA
Reg.
No.:
10182­
415),
Heritage
®
Fungicide
(
EPA
Reg.
No.:
100­
1093),
Quilt
 
Fungicide
(
EPA
Reg.
No.:
110­
1178)

TABLE
2.0.2
Physicochemical
Properties
Parameter
Value
Melting
point/
range
114­
116
°
C
pH
6.4
Density
1.25
g/
cm3
Water
solubility
(
mg/
L
at
20
°
C)
solvent
solubility
water,
pH
5.2
6.7
mg/
L
water,
pH
7
6.7
mg/
L
water,
pH
9.2
5.9
mg/
L
Solvent
solubility
(
mg/
L
at
20
°
C)
solvent
solubility
n­
hexane
0.057
mg/
mL
methanol
20
mg/
mL
ethyl
acetate
130
mg/
mL
toluene
55
mg/
mL
acetone
86
mg/
mL
dichloromethane
400
mg/
mL
Vapor
pressure
at
25
°
C
1.1
x
10­
13
kPa
=
8.2
x
10­
13
mg
Hg
Dissociation
constant
(
pKa)
Not
dissociable
Octanol/
water
partition
coefficient
Log(
KOW)
log
POW
=
2.5
UV/
visible
absorption
spectrum
Not
available
13
of
52
3.0
HAZARD
CHARACTERIZATION
All
toxicological
data
requirements
for
azoxystrobin
technical
have
been
satisfied.
HED
has
a
high
degree
of
confidence
in
the
toxicology
database.
Acute
data
requirements
for
all
enduse
products
have
been
satisfied.

3.1
Hazard
Profile
The
acute
toxicity
findings
for
azoxystrobin
are
presented
below
in
Table
3.
The
scientific
and
regulatory
quality
of
the
azoxystrobin
database
is
high,
and
so
is
the
confidence
in
hazard
assessments
based
on
these
data.

TABLE
3.
1
Acute
Toxicity
Data
on
Azoxystrobin
Technical
Guideline
No.
Study
Type
MRID
#
Results
Toxicity
Category
870.1100
Acute
Oral
­
Rat
43678122
LD50
>
5000
mg/
kg
(
Limit
Test)
in
Males
&
Females
IV
870.1200
Acute
Dermal
­
Rat
43678124
LD50
>
2000
mg/
kg
(
Limit
Test)
in
Males
&
Females
III
870.1300
Acute
Inhalation
­
Rat
43678126
LC50
Males
=
0.962
mg/
L
(
95%
C.
I.
=
0.674)
Females
=
0.698
mg/
L
(
95%
C.
I.
=
0.509,
2.425)
The
combined
LC50
was
not
calculated
due
to
mortality
pattern.
III
870.2400
Primary
Eye
Irritation
­
Rabbit
43678128
Slight
to
moderate
erythema
and
slight
chemosis
in
all
rabbits
within
one
hour,
but
effects
resolved
within
48
hours
of
treatment.
III
870.2500
Primary
Skin
Irritation
­
Rabbit
43678130
Very
slight
erythema
and
edema
that
persisted
for
three
days
on
one
rabbit
and
for
one
hour
on
another.
IV
870.2600
Dermal
Sensitization
­
Guinea
Pig
43678132
No
erythema
or
edema
were
found
38
or
48
hrs
after
challenge
with
test
material.
Not
a
dermal
sensitizer
3.2
FQPA
Considerations
On
August
15,
2000,
the
HIARC
reaffirmed
the
FQPA
Safety
Factor
Committee's
conclusions
that
the
available
studies
indicated
no
increased
susceptibility
of
rats
or
rabbits
to
in
utero
and/
or
postnatal
exposure
to
azoxystrobin
(
HED
Document
No.
013102,
dated
12/
10/
96).
The
FQPA
Safety
Factor
Committee
considered
the
available
toxicology
data
base
adequate
for
an
FQPA
assessment
and
recommended
that
the
10­
fold
safety
factor
for
increased
susceptibility
of
infants
and
children
(
as
required
by
Food
Quality
Protection
Act
of
August
3,
1996)
be
14
of
52
removed
(
i.
e.,
reduced
to
1x).
The
azoxystrobin
risk
assessment
team
evaluated
the
quality
of
the
exposure
data
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
be
reduced
to
1x.
The
recommendation
is
based
upon
the
following:

·
The
toxicology
data
base
is
complete;
·
The
developmental
and
reproductive
toxicity
data
did
not
indicate
increased
susceptibility
of
rats
or
rabbits
to
in
utero
and/
or
postnatal
exposure;
·
The
acute
and
chronic
dietary
food
exposure
assessments
utilize
existing
and
proposed
tolerance
level
residues
and
100%
crop
treated
information
for
all
commodities
(
NOTE:
The
chronic
dietary
exposure
analysis
for
azoxystrobin
is
a
Tier
2
assessment
using
some
percent
crop
treated
(%
CT)
information
for
selected
crops).
By
using
these
screeninglevel
assessments,
actual
exposures/
risks
will
not
be
underestimated;
·
The
exposure
assessments
will
not
underestimate
the
potential
dietary
(
food
and
drinking
water)
or
non­
dietary
exposures
for
infants
and
children
from
the
use
of
azoxystrobin;
·
The
dietary
drinking
water
assessment
utilizes
water
concentration
values
generated
by
model
and
associated
modeling
parameters
which
are
designed
to
provide
conservative,
health
protective,
high­
end
estimates
of
water
concentrations
which
are
not
likely
to
be
exceeded;
and
·
The
residential
postapplication
assessment
is
based
upon
the
residential
SOPs.
The
assessment
is
based
upon
surrogate
study
data.
These
data
are
reliable
and
are
not
expected
to
underestimate
risk
to
adults
or
children.
The
residential
SOPs
are
based
upon
reasonable
"
worst­
case"
assumptions
and
are
not
expected
to
underestimate
risk.

3.3
Dose­
Response
Assessment
A
summary
of
the
dose
levels
and
endpoints
for
use
in
risk
assessment
are
presented
in
Table
4
below.

TABLE
3.3
Summary
of
Toxicological
Doses
and
Endpoints
for
Azoxystrobin
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
general
population
including
infants
and
children
NOAEL
<
200
mg/
kg/
day
UF
=
300
Acute
RfD
=
0.67
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
0.67
mg/
kg/
day
Acute
Neurotoxicity
­
Rat
LOAEL
=
200
mg/
kg
based
on
diarrhea
at
two­
hours
post
dose
at
all
dose
levels
up
to
and
including
the
LOAEL.

Chronic
Dietary
all
populations
NOAEL=
18
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.18
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.18
mg/
kg/
day
Combined
Chronic
Toxicity/
Carcinogenicity
Feeding
study
­
Rat
LOAEL
in
males/
females
=
34/
117
mg/
kg/
day
based
on
reduced
body
weights
in
both
sexes
and
bile
duct
lesions
in
males.
Page
15
of
52
TABLE
3.3
Summary
of
Toxicological
Doses
and
Endpoints
for
Azoxystrobin
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Short­
Term
(
1­
30
days)
Incidental
Oral
(
Residential)
NOAEL=
25
mg/
kg/
day
UF
=
100
FQPA
SF
=
1X
Prenatal
Developmental
Oral
Toxicity
­
Rat
LOAEL
=
100
mg/
kg/
day
based
on
increased
maternal
diarrhea,
urinary
incontinence,
and
salivation.

Intermediate­
Term
(
1
week
to
6months)
Incidental
Oral
(
Residential)
NOAEL=
20
mg/
kg/
day
UF
=
100
FQPA
SF
=
1X
90­
Day
Feeding
­
Rat
LOAEL
=
211/
223
mg/
kg/
day
in
males/
females
based
on
decreased
body
weight
gain
in
both
sexes
and
clinical
signs
indicative
of
reduced
nutrition.

Short­,
Intermediate­,
and
Long­
Term
Dermal
(
Occupational/
Residential)
none
No
dermal
or
systemic
toxicity
was
seen
at
the
limit
dose
(
1000
mg/
kg/
day).
This
risk
assessment
is
not
required.
21­
Day
Repeated
Dose
Dermal
­
Rat
Short­
Term
(
1­
30
days)
Inhalation
(
Occupational/
Residential)
Oral
NOAEL=
25
mg/
kg/
day
Use
route­
to­
route
extrapolation
(
inhalation
absorption
rate
=
100%).
LOC
for
MOE
=
100
(
Occupational/
Residential)
Prenatal
Developmental
Oral
Toxicity
­
Rat
LOAEL
=
100
mg/
kg/
day
based
on
increased
maternal
diarrhea,
urinary
incontinence,
and
salivation.

Intermediate­
Term
(
1
week
to
6months)
Inhalation
(
Occupational/
Residential)
Oral
NOAEL=
20
mg/
kg/
day
Use
route­
to­
route
extrapolation
(
inhalation
absorption
rate
=
100%).
LOC
for
MOE
=
100
(
Occupational/
Residential)
90­
Day
Feeding
­
Rat
LOAEL
=
211/
223
mg/
kg/
day
in
males/
females
based
on
decreased
body
weight
gain
in
both
sexes
and
clinical
signs
indicative
of
reduced
nutrition.

Long­
Term
(>
180
days)
Inhalation
NOAEL
=
N/
A
This
risk
assessment
is
not
applicable
to
the
use
scenario
for
azoxystrobin.

Cancer
"
Not
Likely"
NA
HED
RfD/
Peer
Review
Committee,
11/
7/
96
NOAEL
=
no
observable
adverse
effect
level;
LOAEL
=
lowest
observable
adverse
effect
level;
UF
=
uncertainty
factor;
MOE
=
margin
of
exposure;
LOC
=
level
of
concern;
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic);
RfD
=
reference
dose;
NA
=
not
applicable.

The
HED
RfD/
Peer
Review
Committee,
in
its
meeting
of
November
7,
1996,
determined
that
azoxystrobin
should
be
classified
as
"
not
likely
to
be
a
human
carcinogen"
according
to
the
Page
16
of
52
revised
Cancer
Guidelines,
based
on
lack
of
evidence
of
carcinogenicity
in
the
long­
term
rat
and
mouse
feeding
studies
(
HED
Document
No.
012133,
1/
14/
97).
Therefore,
cancer
risk
assessments
were
not
performed.

The
HIARC
recommended
the
following
for
aggregation
of
exposures
from
azoxystrobin:

°
For
acute
aggregate
exposure
risk
assessment,
combine
the
high­
end
exposure
values
from
food
+
water
and
compare
it
to
the
acute
RfD
(
0.67
mg/
kg)
established
for
the
general
population.
°
For
chronic
aggregate
exposure
risk
assessment,
combine
the
average
exposure
values
from
food
+
water
and
compare
it
to
the
chronic
RfD
(
0.18
mg/
kg/
day).
°
For
short­
and
intermediate­
term
aggregate
exposure
risk
assessment,
the
short­
term
and
intermediate­
term
inhalation
exposures
should
be
converted
to
oral
equivalent
doses
(
using
100%
inhalation
absorption
rate),
and
should
be
added
to
the
oral
exposures
(
from
food
+
water)
and
compared
to
the
respective
oral
NOAELs.
°
No
long­
term
aggregate
risk
is
required
due
to
the
lack
of
long­
term
exposure.

3.4
Endocrine
Disruption
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
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
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

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

4.0
EXPOSURE
ASSESSMENT
4.1
Summary
of
Proposed
Uses
Details
for
the
uses
of
azoxystrobin
in
PP#
5E6916,
05FL11,
and
05TN11
are
presented
in
Table
5.
Page
17
of
52
Table
4.
Summary
of
Directions
for
Use
of
Azoxystrobin.

Application
Equipment
Formul.
tn
[
EPA
Reg.
No.]
Applic.
Rate
(
lb
ai/
A)
Max.
#

Appl.
per
Season
Max.
Seasonal
Appl.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Citrus
Fruit
(
Calamondin,
Citron,
Citrus
hybrids,
Grapefruit,
Kumquat,
Lemon,
Lime,
Mandarin,
Orange
[
sour
and
sweet],
Pummelo,
Salsuma
mandarin,
Tangerine,

including
all
cultivars
and/
or
hybrids
of
these)

Abound
®

Flowable
Fungicide
[
100­
1098]
For
high­
volume:

0.0052
 
0.042
lb
ai/
gal
solution
For
low
volume:

0.021
 
0.15
lb
ai/
gal
soln
For
dip:

0.0052
 
0.010
lb
ai/
gal
soln
Not
specified
For
highvolume
(
dilute)
applications:

T­
Jet,
Flooders
or
similar
systems
For
low
volume
(
concentrate)

applications:

use
a
controlleddroplet
type
of
applicator
or
similar
system
For
dip
applications:

use
containers
that
hold
100
gal
+
Amistar
®
Fungicide
[
100­
1164]
For
high­
volume:

0.013
 
0.10
lb
ai/
gal
solution
For
low
volume:

0.051
 
0.37
lb
ai/
gal
soln
For
dip:

0.013
 
0.026
lb
ai/
gal
soln
2
(
postharvest
specificall
y)
Not
specified
0
 
REI
=
4
hours
 
Use
as
a
dip,
drench,
flood
or
spray
 
For
high
volume
applications:
mix
32
 
64
fl
oz
of
Abound/
Amistar
in
25
 
100
gal
of
an
appropriate
water,

wax/
oil
emulsion
or
aqueous
dilution
of
a
wax/
oil
emulsion
for
crop
being
treated
 
For
low
volume
applications:
mix
32
 
64
fl
oz
of
Abound/
Amistar
in
7
 
25
gal
of
water,
wax/
oil
emulsion,
or
aqueous
dilution
of
wax/
oil
emulsion
for
the
crop
being
treated;
Apply
to
250,000
lb
of
fruit
 
For
dip
applications:
mix
32
 
64
fl
oz
of
Abound/
Amistar
in
100
gal
of
water,
wax/
oil
emulsion,

or
aqueous
dilution
of
wax/
oil
emulsion;
dip
for
approximately
30
sec
and
allow
fruit
to
drain
 
For
maximum
decay
control,
treat
citrus
fruit
once
before
storage
and
once
after
storage,
just
prior
to
marketing
*
For
dip
application
the
label
instructs
the
user
to
use
fl
oz
of
Amistar
 
the
label
should
be
amended
to
refer
to
Amistar
in
oz,
since
it
is
a
WDG
formulation.
Page
18
of
52
Table
4.
Summary
of
Directions
for
Use
of
Azoxystrobin.

Application
Equipment
Formul.
tn
[
EPA
Reg.
No.]
Applic.
Rate
(
lb
ai/
A)
Max.
#

Appl.
per
Season
Max.
Seasonal
Appl.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Peppers
and
other
Fruiting
Vegetables
(
except
cucurbits
and
tomatoes)

(
Bell
Pepper,
Non­
Bell
Pepper,
Eggplant,
Groundcherry,
Okra,
Pepino,
Tomatillo)

Abound
®

Flowable
Fungicide
[
100­
1098]
0.10
­
0.25
(
6.2
 
15.4
fl
oz
product/
A)

0.28
 
0.57
(
0.4
 
0.8
fl
oz
product/
1000
row
feet
 
for
soilborne
diseases)
1.0
(
1.92
quarts
per
acre
per
season)

Ground,

Aerial
and
Chemigation
Equipment
Amistar
®
Fungicide
0.10
 
0.25
(
2
­
5
oz
product/
A)

0.27
 
0.54
(
0.125
 
0.25
fl
oz
product/
1000
row
feet
 
for
soilborne
diseases)
Not
specified
1.0
(
1.25
lbs
product
per
acre
per
season)
0
 
REI
=
4
hours
 
Abound/
Amistar
should
be
integrated
into
an
overall
disease
management
strategy
that
includes
selection
of
varieties
with
tolerance
to
disease
and
removal
of
plant
debris
in
which
inoculum
overwinters
 
Do
not
make
more
than
one
application
of
Abound/
Amistar
or
any
other
strobilurin
fungicide
before
alternating
to
a
fungicide
with
a
different
mode
of
action
 
Abound/
Amistar
applications
should
begin
prior
to
disease
development
and
continue
throughout
the
season
on
a
7
 
14
day
schedule,
following
the
resistance
management
guidelines
Page
19
of
52
Table
4.
Summary
of
Directions
for
Use
of
Azoxystrobin.

Application
Equipment
Formul.
tn
[
EPA
Reg.
No.]
Applic.
Rate
(
lb
ai/
A)
Max.
#

Appl.
per
Season
Max.
Seasonal
Appl.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Foliage
of
Legume
Vegetables
(
Any
cultivar
of
bean
[
Phaseolus
spp.]
and
field
pea
[
Pisum
spp])

Abound
®

Flowable
Fungicide
[
100­
1098]
0.10
­
0.25
(
6.2
 
15.4
oz
product/
A)
1.5
(
2.88
quarts
product/
A/
season)

Ground,

Aerial
and
Chemigation
Equipment
Amistar
®
Fungicide
[
100­
1164]
0.10
­
0.25
(
6.2
 
15.4
oz
product/
A)
Not
specified
1.5
(
2.88
quarts
product/
A/
season)
0
 
REI
=
4
hours
 
Abound/
Amistar
should
be
integrated
into
an
overall
disease
management
stragety
that
includes
selection
of
varieties
with
disease
tolerance,
proper
timing
an
dplacement
of
irrigation,
crop
rotation
and
crop
residue
management
 
Do
not
apply
more
than
two
sequential
applications
of
Abound/
Amistar
or
other
Group
11
fungicides
before
alternation
with
a
fungicide
that
has
a
different
mode
of
action
 
Abound/
Amistar
applications
should
begin
prior
to
disease
development
and
continue
throughout
the
season
every
7­
14
days
following
the
resistance
management
guidelines
 
Use
the
higher
rates
under
severe
disease
pressure
*
For
the
Amistar
®
label,
the
application
rate
given
in
oz
product/
A
do
not
match
lb
ai/
A
­
the
label
should
be
amended,
and
read
2
 
5
oz
product/
A;
for
the
max
appl
rate,
the
oz/
product/
A
should
be
amended
to
read
30
oz
product/
A/
season
Page
20
of
52
Table
4.
Summary
of
Directions
for
Use
of
Azoxystrobin.

Application
Equipment
Formul.
tn
[
EPA
Reg.
No.]
Applic.
Rate
(
lb
ai/
A)
Max.
#

Appl.
per
Season
Max.
Seasonal
Appl.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Legume
Vegetables,
dry
and
succulent
(
grain,
sweet,
white
and
white
sweet
lupin;
adzuki,
asparagus,
broad
(
fava),
field,
kidney,
lablab
(
hyacinth),
lima,
moth,
mung,
navy,
pinto,
rice,
runner,
snap,

sword,
tepary,
urd,
wax
and
yardlong
beans;
blackeyed,
cow,
catjang,
Crowder,
dwarf,
edible­
pod,
English,
garden,
green,
field,
pigeon,
snow,
sugar
snap,

southern
peas;
Chinise
longbean;
chickpea
(
garbanzo
bean);
guar;
jackbean;
and
lentils)

Abound
®

Flowable
Fungicide
[
100­
1098]
0.10
 
0.25
(
6.2
 
15.4
fl
oz/
product/
A)

0.28
 
0.57
(
0.40
 
0.80
fl
oz
product/
1000
row
feet
 
for
soilborne
diseases)
1.5
(
2.88
quarts
product/
A/
season)

Ground,

Aerial
and
Chemigation
Equipment
Amistar
®
Fungicide
[
100­
1164]
0.10
 
0.25
(
2
 
5
oz
product/
A)

0.27
 
0.54
(
0.125
 
0.25
fl
oz
product/
1000
row
feet
 
for
soilborne/
seedling
disease
control)
Not
specified
1.5
(
1.88
lbs
product/
A/
season)
0
 
REI
=
4
hours
 
Abound/
Amistar
should
be
integrated
into
an
overall
disease
management
strategy
that
includes
selection
of
varieties
with
disease
tolerance,
proper
timing
and
placement
of
irrigation,
crop
rotation
and
crop
residue
management
 
Do
not
apply
more
than
two
sequential
applications
of
Abound/
Amistar
or
other
Group
11
fungicides
before
alternation
with
a
fungicide
that
has
a
different
mode
of
action
 
Abound/
Amistar
applications
should
begin
prior
to
disease
development
and
continue
throughout
the
season
every
7
 
14
days
following
the
resistance
management
guidelines
 
Use
the
higher
rates
under
severe
disease
pressure
Page
21
of
52
Table
4.
Summary
of
Directions
for
Use
of
Azoxystrobin.

Application
Equipment
Formul.
tn
[
EPA
Reg.
No.]
Applic.
Rate
(
lb
ai/
A)
Max.
#

Appl.
per
Season
Max.
Seasonal
Appl.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Forage,
Fodder,
Straw
and
Hay
Grass
and
Nongrass
(
alfafa,
bean,
velvet,
clover,
kudzu,
lespedeza,
lupin,
sainfoin,
trefoil,
vetch,
and
crown
and
milk
vetch)

Abound
®

Flowable
Fungicide
[
100­
1098]
0.10
­
0.25
(
6.2
 
15.4
oz
product/
A)
For
pure
stands
of
nongrass
forage:
1.5
(
2.88
quarts
product/
A/
season)

For
mixed
grass
and
nongrass
stands:

0.75
(
1.44
quarts
product/
A/
season)

Ground,

Aerial
and
Chemigation
Equipment
Amistar
®
Fungicide
[
100­
1164]
0.10
­
0.25
(
2
­
5
oz
product/
A)
Not
specified
For
pure
stands
of
nongrass
forage:
1.5
(
1.88
lbs
product/
A/
season)

For
mixed
grass
and
nongrass
stands:

0.75
(
0.93
lbs
product/
A/
season)
For
pure
stands
of
nongrass
forage:

0
For
mixed
grass
and
nongrass
stands:

8
 
REI
=
4
hours
 
Abound/
Amistar
should
be
integrated
into
an
overall
disease
management
strategy
that
includes
selection
of
varieties
with
disease
tolerance,
proper
timing
and
placement
of
irrigation,
crop
rotation
and
crop
residue
management
 
Do
not
apply
more
than
two
sequential
applications
of
Abound/
Amistar
or
other
Group
11
fungicides
before
alternation
with
a
fungicide
that
has
a
different
mode
of
action
 
For
management
of
Asian
soybean/
bean
rust,

Abound/
Amistar
applications
should
begin
prior
to
disease
developmentand
continue
throughout
the
season
every
7
 
14
days
following
the
resistance
management
guidelines
 
Use
the
higher
rates
under
severe
disease
pressure
 
For
management
of
outbreaks
of
Asian
rust
on
alternate
host
species
such
as
kudzu,
llespedeza,
trefoil
and
vetch,
apply
Abound/
Amistar
to
forages
grown
in
the
vicinity
of
soybeans
and
other
legume
crops
(
beans
and
peas)
as
part
of
an
Asian
rust
disease
management
strategy
 
Not
for
use
on
rangeland
Page
22
of
52
Residential
uses
are
not
proposed
in
this
petition.
However,
azoxystrobin
is
currently
registered
for
use
on
residential
turfgrass
and
ornamentals,
as
well
as
indoor
surfaces.
Other
proposed
uses
of
azoxystrobin
also
include
applications
to
tobacco,
greenhouse
roses,
and
indoor
carpets/
other
surfaces.
Short­
term
exposures
may
occur
during
adult
residential
handling
activities.
Non­
occupational
handler
exposure
may
occur
from
mixing,
loading
and
applying
to
turf,
for
spot
application
with
a
low­
pressure
handwand,
for
broadcasting
with
a
garden
hose­
end
sprayer
to
turf,
and
to
indoor
surfaces.
Short­
and
intermediate­
term
exposures
may
occur
during
postapplication
activities
for
adults
and
children
(
however,
adult
postapplication
exposure
was
not
assessed
because
no
dermal
hazard
endpoint
was
identified).
Toddlers
may
experience
shortand
intermediate­
term
exposure
to
azoxystrobin
via
incidental
oral
(
non­
dietary)
ingestion
during
postapplication
activities
on
treated
turf
(
i.
e.,
hand­
to­
mouth,
object­
to­
mouth
[
turfgrass],
and
soil
ingestion)
and
during
postapplication
activities
on
treated
indoor
surfaces
(
i.
e.,
hand­
tomouth
Details
of
residential
use
and
resulting
exposure
estimates
are
presented
later
in
this
document.

4.2
Dietary
Exposure/
Risk
Pathway
4.2.1
Residue
Profile
Metabolism
in
Plants
and
Livestock
Adequate
metabolism
studies
on
grapes,
peanuts,
and
wheat
were
submitted
in
conjunction
with
earlier
petitions.
Azoxystrobin
(
methyl
(
E)­
2­(
2­(
6­(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy)
phenyl)­
3­
methoxyacrylate)
undergoes
photochemical
isomerization
to
produce
the
Z­
isomer
(
methyl
(
Z)­
2­(
2­(
6­(
2­
cyanophenoxy)
pyrimidin­
4­
yloxy)
phenyl)­
3
methoxyacrylate)
and
is
extensively
metabolized
in
plants.
The
parent
compound
undergoes
cleavage
of
the
ether
linkages
between
the
phenylacrylate
and
pyrimidinyl
rings
and
the
cyanophenyl
and
pyrimidinyl
rings,
with
subsequent
oxidation,
hydrolysis,
and/
or
reduction
of
the
primary
metabolites
to
form
numerous
secondary
metabolites.
Azoxystrobin
was
found
to
be
systemic.
The
HED
MARC
has
determined
that
the
residues
of
concern
in/
on
plants
for
the
tolerance
expression
and
risk
assessment
purposes
are
azoxystrobin
and
its
Z­
isomer.

Adequate
ruminant
and
poultry
metabolism
studies
were
submitted
in
conjunction
with
earlier
petitions.
The
HED
MARC
has
determined
that
the
residue
of
concern
in
livestock
is
parent
azoxystrobin
only.

Analytical
Method
for
Plants
and
Livestock
Method
RAM
243/
04
has
undergone
method
validation
by
the
Analytical
Chemistry
Branch
(
ACB),
BEAD.
BEAD
comments
have
been
incorporated
and
the
revised
method
designated
RAM
243,
"
Residue
Analytical
Method
for
the
Analysis
of
ICIA5504
and
R230310
in
Grain
and
Grapes
for
EPA
Confirmation,"
dated
5/
15/
98;
MRID
44595105,
has
been
submitted
to
FDA
for
inclusion
in
PAM
II.
Adequate
methodology
is
available
for
enforcement
Page
23
of
52
of
the
established
tolerances
on
livestock.
The
GC
method
255/
01
has
been
validated
by
the
EPA
analytical
laboratory
for
the
analysis
of
milk
and
livestock
tissues.
The
EPA
laboratory's
written
report
with
an
EPA
addendum
to
accompany
the
method,
and
the
method,
will
be
submitted
to
FDA
for
inclusion
in
PAM,
Vol.
II.

Citrus
samples
were
analyzed
for
residues
of
azoxystrobin
and
its
Z­
isomer
using
Zeneca
Report
Number
RAM
243/
04,
via
GC/
NPD
with
minor
modifications.
LOD
for
azoxystrobin
and
Z­
isomer
were
established
at
0.0092
ppm
and
0.0065
ppm
in
grapefruit,
0.011
ppm
and
0.0074
ppm
in
orange,
and
0.0077
ppm
and
0.0056
ppm
in
lemon.
LOQ
for
azoxystrobin
and
Zisomer
were
established
at
0.028
ppm
and
0.020
ppm
in
grapefruit,
0.034
ppm
and
0.022
ppm
in
orange,
and
0.023
ppm
and
0.017
ppm
in
lemon.

Multiresidue
Methods
Data
have
previously
been
submitted
pertaining
to
the
multiresidue
methods
testing
of
azoxystrobin
in
conjunction
with
the
grape
tolerance
petition.
The
data
indicate
that
azoxystrobin
could
not
be
recovered
through
application
of
the
multiresidue
protocols.
These
data
have
been
forwarded
to
FDA.

Storage
Stability
Data
Previously
submitted
storage
stability
data
indicate
that
residues
of
azoxystrobin
and
the
Z­
isomer
are
stable
in
oil
seed
rape,
soybean
meal,
corn
grits,
carrot
root,
leaf
lettuce,
and
wheat
forage
for
at
least
two
years
under
frozen
storage.
The
information
is
adequate
for
the
purpose
of
supporting
the
proposed
tolerances.

Citrus
samples
were
stored
frozen
for
up
to
411
days
between
sampling
and
extraction.
Previously
submitted
storage
stability
data
indicates
that
residues
of
azoxystrobin
and
the
Zisomer
are
stable
in
orange
oil,
orange
juice,
and
orange
pulp
for
at
least
two
years
under
frozen
storage.
The
information
is
adequate
for
the
purpose
of
supporting
the
azoxystrobin
and
the
Zisomer
residue
data
on
citrus.

Magnitude
of
the
Residue
Foliage
of
Legume
Vegetables,
Group
7
No
new
residue
field
trial
data
were
submitted
for
the
foliage
of
legume
vegetables,
Group
7.
The
representative
commodities
for
Group
7
are
foliar
portions
of
any
cultivar
of
bean,
field
pea,
and
soybean.
RAB2
previously
stated
that
as
long
as
the
use
pattern
is
similar
and
the
proposed
field
trial
residue
data
supporting
a
tolerance
for
Group
4
are
submitted
and
deemed
adequate,
it
will
be
appropriate
to
request
a
tolerance
for
Group
7
at
the
same
level
as
Group
4.
The
requirements
set
forth
by
RAB2
for
the
establishment
of
an
azoxystrobin
tolerance
on
the
foliage
of
legume
vegetables,
Group
7
have
been
satisfied.
TRB
recommends
for
the
establishment
of
a
tolerance
at
30.0
ppm
for
the
residues
of
azoxystrobin
on
vegetables,
foliage
of
legume,
Group
7.
Since
the
proposed
tolerance
on
Group
7
will
include
a
soybean
hay
and
forage,
the
existing
tolerances
on
those
commodities
should
be
removed.
Page
24
of
52
Fruiting
Vegetables,
Group
8
(
Except
Tomato)

No
new
residue
field
trial
data
were
submitted
for
the
vegetable,
fruiting,
Group
8
(
except
tomato).
There
are
tolerances
established
for
members
of
Group
8:
peppers,
okra,
and
eggplant
at
2.0
ppm,
and
tomato
at
0.2
ppm
(
CFR
§
180.507).
Although
all
the
existing
residue
data
on
the
Group
8
representative
commodities
were
determined
to
be
sufficient
to
establish
a
crop
group
tolerance,
risk
cup
issues
at
the
time
precluded
increasing
the
tomato
tolerance
and
separate
tolerances
were
requested
on
okra
and
eggplant.
Since
the
existing
data
were
determined
to
be
adequate
for
a
crop
group
tolerance,
there
is
sufficient
data
to
support
the
petition
for
the
requested
subgroup.
However,
the
commodity
definition
presented
by
the
petitioner
is
incorrect.
A
new
Section
F
should
be
submitted
requesting
a
tolerance
for
the
residues
of
azoxystrobin
at
2.0
ppm
on
vegetables,
fruiting,
Group
8
(
except
tomato).
The
existing
separate
tolerances
on
pepper,
okra,
and
eggplant
should
be
removed.

Pea
and
Bean,
Succulent
and
Dried
Shelled
(
Except
Soybeans),
Subgroups
6B
and
6C
No
new
residue
field
trial
data
were
submitted
for
the
pea
and
bean,
succulent
shelled,
Subgroup
6B;
and
pea
and
bean,
dried
shelled,
except
soybean,
Subgroup
6C.
The
existing
tolerance
commodity
definitions
are:
pea
and
bean,
dried
shelled,
except
soybean,
subgroup,
except
cowpea,
and
field
pea;
and
pea
and
bean,
succulent
shelled,
subgroup,
except
cowpea.
The
subgroup
tolerances
excluded
cowpea
and
field
pea
because
there
was
no
residue
field
data
for
forage,
hay,
and/
or
silage
as
livestock
feeds.
In
order
to
satisfy
the
data
requirements,
RAB3
previously
indicated
that
residue
data
on
the
representative
crops
of
Group
7
were
required.
However,
as
stated
above,
the
requirements
set
forth
by
RAB2
for
the
establishment
of
an
azoxystrobin
tolerance
on
vegetables,
foliage
of
legume,
Group
7
have
been
satisfied.
Therefore,
no
further
residue
field
trial
data
is
required.
TRB
recommends
for
the
establishment
of
tolerances
at
0.5
ppm
for
the
residues
of
azoxystrobin
on
pea
and
bean,
succulent
shelled,
Subgroup
6B;
and
pea
and
bean,
dried
shelled,
except
soybean,
Subgroup
6C.

Nongrass
Animal
Feeds,
Group
18
No
new
residue
field
trial
data
were
submitted
for
the
animal
feed,
nongrass,
Group
18.
IR­
4
requested
that
the
Agency
use
data
supporting
the
tolerances
for
vegetable,
leafy,
except
Brassica,
Group
4
at
30.0
ppm,
Brassica,
leafy
greens,
Subgroup
5B
at
25
ppm,
and
soybean,
hay
at
55.0
ppm
to
support
the
establishment
of
tolerances
for
animal
feed,
nongrass,
Group
18,
forage
at
30.0
ppm
and
animal
feed,
nongrass,
Group
18,
hay
at
55.0
ppm.
ChemSAC
has
determined
that
the
existing
data
cited
by
the
petitioner
is
not
sufficient
to
support
the
requested
tolerance.
TRB
recommends
against
the
proposed
tolerances
on
animal
feed,
nongrass,
Group
18,
forage
and
hay.
However,
TRB
concluded,
based
on
the
existing
use
on
soybeans,
which
has
the
same
use
pattern
as
that
proposed
for
animal
feed,
nongrass,
Group
18,
a
reduced
number
of
residue
field
trials
would
be
appropriate.
Six
residue
field
trials
each
with
the
appropriate
geographic
distribution
on
the
two
representative
crops
for
animal
feed,
nongrass,
Group
18,
alfalfa
and
clover
are
required
to
support
a
proposed
azoxystrobin
tolerance.
Page
25
of
52
Citrus
IR­
4
has
submitted
residue
data
for
azoxystrobin
and
its
Z­
isomer
on
citrus
treated
with
both
preharvest
and
postharvest
applications.
The
submitted
data
were
obtained
from
trials
conducted
in
Florida
(
1
trial),
Texas
(
1
trial),
and
California
(
4
trials)
(
EPA
Region
III,
VI,
and
X,
respectively).
Each
of
the
field
site
consisted
of
one
untreated
control
plot
and
one
treated
plot.
The
total
numbers
of
citrus
trials,
as
well
as
the
number
of
trials
per
site,
are
not
in
compliance
with
the
recommended
numbers
in
the
EPA
Residue
Chemistry
Test
Guidelines,
OPPTS
860.1500­
Crop
Field
Trials.
However,
since
the
study
was
conducted
to
obtain
data
for
the
post­
harvest
use,
only,
the
number
and
location
of
the
trials
are
adequate.

At
each
test
location,
azoxystrobin
was
applied
as
Azoxystrobin
80WG,
which
is
a
water
dispersible
granule
formulation
containing
80%
azoxystrobin.
Each
treated
plot
received
two
foliar
applications
at
the
single
application
rate
of
~
0.25
lb
ai/
A
with
6
to
8
days
between
applications.
Mature
citrus
fruits
were
collected
on
the
day
of
the
final
application.
Adequate
amounts
of
treated
fruit
were
collected
from
each
site
for
separate
post­
harvest
treatments.
Additional
oranges
from
a
California
trial
were
collected
to
generate
control
peel
and
flesh
samples
as
well
as
post­
harvest
dip
without
storage
wax
treatment
samples.

Six
different
types
of
post­
harvest
treatment
were
tested
in
the
study:
1)
dip
with
Decco
202
storage
wax;
2)
packing­
line
spray
with
storage
wax;
3)
dip
without
wax;
4)
packing­
line
spray
without
wax
followed
by
application
of
Decco
400
shipping
wax;
5)
dip
with
storage
wax
followed
by
dip
without
storage
wax;
and,
6)
packing­
line
spray
with
storage
wax,
followed
by
wash
with
Decco
cleaner,
followed
by
packing­
line
spray
without
storage
wax,
followed
by
application
of
shipping
wax.
All
post­
harvest
test
solutions
contained
Azoxystrobin
80WG
and
were
applied
at
1.0
lb
ai/
100
gal
water
(
dip)
and
1.0
lb
ai/
250,000
lb
fruits
(
packing­
line
spray).

Samples
were
analyzed
for
residues
of
azoxystrobin
and
its
Z­
isomer
via
GC/
NPD.
Extraction
and
analysis
of
all
samples
for
azoxystrobin
and
Z­
isomer
were
conducted
using
Zeneca
Report
Number
RAM
243/
04,
with
minor
modifications.
LOD
for
azoxystrobin
and
Zisomer
were
established
at
0.0092
ppm
and
0.0065
ppm
in
grapefruit,
0.011
ppm
and
0.0074
ppm
in
orange,
and
0.0077
ppm
and
0.0056
ppm
in
lemon.
LOQ
for
azoxystrobin
and
Z­
isomer
were
established
at
0.028
ppm
and
0.020
ppm
in
grapefruit,
0.034
ppm
and
0.022
ppm
in
orange,
and
0.023
ppm
and
0.017
ppm
in
lemon.
Azoxystrobin
residues
found
in
grapefruit,
orange,
and
lemon
samples
that
were
only
treated
in
the
field
ranged
from
0.098
to
0.29
ppm,
0.075
to
1.98
ppm,
and
0.29
to
0.69
ppm,
respectively.
Azoxystrobin
residues
detected
in
grapefruit,
orange
and
lemon
samples
that
received
preharvest
as
well
as
postharvest
dip
treatments
ranged
from
1.19
to
5.43
ppm,
1.21
to
3.99
ppm,
and
1.47
to
9.18
ppm,
respectively.
Azoxystrobin
residues
detected
in
grapefruit,
orange,
and
lemon
samples
that
received
preharvest
as
well
as
packingline
spray
postharvest
treatments
ranged
from
0.41
to
0.92
ppm,
0.37
to
1.08
ppm,
and
0.72
to
1.57
ppm.
Finally,
residues
in
the
orange
peel
and
flesh
samples
ranged
from
4.69
to
5.52
ppm
and
0.53
to
0.75
ppm,
respectively.
No
Z­
isomer
residues
above
the
lower
limit
of
method
validation
(
LLMV)
of
0.02
ppm
were
observed
in
any
sample.
Page
26
of
52
TABLE
4.2.1
Summary
of
Residue
Data
from
Citrus
Field
Trials
with
Azoxystrobin.

Total
Application
Rate
1
Residue
Levels
(
ppm)
Analyte
Preharvest
Rate
(
lb
ai/
A)
Post­
harvest
dip
(
lb
ai/
100
gal.)
Post­
harvest
spray
(
lb
ai/
250,000
lbs.
fruit)
PHI
(
days)

n
Min.
Max.
HAFT
2
Median
(
STMdR)
Mean
(
STMR)
Std.
Dev.

1
0
36
1.19
9.18
8.67
2.09
2.87
1.95
Azoxystrobin
0.500
­
0.503
1
0
18
0.37
1.57
1.37
0.79
0.79
0.30
1
0
36
<
0.02
<
0.02
<
0.02
N/
A3
N/
A
N/
A
Z­
isomer
0.500
­
0.503
1
0
18
<
0.02
<
0.02
<
0.02
N/
A
N/
A
N/
A
1
­
Total
Application
Rate
for
Azoxystrobin
and
Z­
isomer
together.
2
­
HAFT
=
Highest
Average
Field
Trial.
3
­
N/
A
­
Not
applicable
The
study
was
conducted
to
demonstrate
the
residues
of
azoxystrobin
in
fruit,
which
were
treated
by
simulated
post­
harvest
applications
following
normal
pre­
harvest
use.
For
this
purpose,
the
number
and
location
of
the
trials
are
adequate.
There
is
an
existing
use
for
azoxystrobin
on
citrus
fruit
with
an
established
tolerance
of
2.0
ppm.
The
petitioner
first
treated
the
fruit
according
to
the
existing
preharvest
use
and
showed
that
quantifiable
residues
were
found
similar
to
those
previously
found
from
the
use.
Those
fruit
were
then
treated
with
azoxystrobin
using
six
different
postharvest
methods.
The
highest
azoxystrobin
residues
were
detected
in
grapefruit,
orange
and
lemon
samples
that
received
preharvest
as
well
as
postharvest
dip
treatments
ranging
from
1.19
to
5.43
ppm,
1.21
to
3.99
ppm,
and
1.47
to
9.18
ppm,
respectively.
The
results
of
the
residue
chemistry
field
trials
indicate
that
the
residues
of
azoxystrobin
following
both
preharvest
and
postharvest
uses
are
not
likely
to
exceed
the
proposed
tolerance
on
citrus
fruit.
Therefore,
TRB
recommends
for
the
increase
in
the
tolerance
on
Citrus
Fruit
to
10.0
ppm,
in
order
to
cover
both
pre­
and
postharvest
uses.

Section
18s
­
Specialty
Legumes
For
05FL11
and
05TN11,
axozystrobin
as
formulated
in
Quilt
 
Fungicide
(
EPA
REG.
No.
110­
1178)
will
be
applied
twice
at
0.014
lb
ai/
A,
up
to
0.028
lb
ai/
A/
season
with
a
0­
day
PHI
on
Group
6
(
except
soybeans)
and
Group
7.
The
use
is
requested
in
response
to
the
threat
of
soybean
rust
on
specialty
legumes.
The
use
will
entail
applications
to
86,502
acres
with
18922.4
gal
of
formulation
(
1173.2
lb
ai
azoxystrobin).
Previous
uses
on
legumes,
except
soybeans,
included
four
applications
of
up
to
0.25
lb
ai/
A
with
a
seasonal
maximum
of
1.0
lb
ai/
A.
Residues
of
azoxystrobin
from
the
established
use
pattern
did
not
exceed
0.5
ppm.
The
requested
the
Section
18
uses
will
not
exceed
the
established
azoxystrobin
tolerances;
therefore
TRB
recommends
for
the
requested
use.
The
product,
Quilt
 
Fungicide
(
EPA
REG.
No.
110­
1178),
also
contains
propiconazole
(
PC
Code:
122101).
The
use
of
this
chemical
on
Group
6
(
except
soybeans)
and
Group
7
commodities
is
not
under
review
here.
Page
27
of
52
Processed
Food
and
Feed
There
are
no
processed
commodities
associated
with
the
uses
of
azoxystrobin
on
foliage
of
legume
vegetables,
Group
7;
vegetables,
fruiting,
Group
8
(
except
tomato);
and
pea
and
bean,
succulent
and
dried
shelled,
except
soybean,
Subgroups
6B
and
6C.

Citrus
No
new
citrus
processing
study
was
submitted
with
this
action.
A
citrus
processing
study
has
been
previously
reviewed.
Total
residues
of
azoxystrobin
and
its
Z­
isomer
did
not
concentrate
in
juice
processed
from
oranges
bearing
detectable
residues.
Total
residues
of
azoxystrobin
and
its
Z
isomer
may
concentrate
1.9­
2.3x
in
dried
pulp
(
avg.
2.1x)
and
4.4­
4.7x
in
oil
(
avg.
4.6x)
processed
from
oranges
bearing
detectable
residues.

The
HAFT
residue
for
citrus
fruit
(
grapefruit,
lemons,
and
oranges)
treated
at
1x
the
maximum
seasonal
rate
from
the
submitted
citrus
field
trials
was
8.67
ppm
(
total
residues
of
azoxystrobin
and
its
Z
isomer).
Based
on
the
HAFT
and
an
average
concentration
factor
of
2.1x,
the
highest
expected
residues
in
dried
citrus
pulp
would
be
18.2
ppm
and
based
on
an
average
concentration
factor
of
4.6x,
the
highest
expected
residues
in
citrus
oil
would
be
39.9
ppm.

Based
on
the
HAFT
residue
for
citrus
fruit
of
8.7
ppm
(
total
residues
of
azoxystrobin
and
its
Z
isomer)
and
the
average
concentration
factors
from
the
previously
submitted
processing
studies
of
2.1x
for
pulp
and
4.6x
for
oil,
the
petitioner's
requests
for
proposed
tolerances
are
adequate.
Therefore,
TRB
recommends
for
azoxystrobin
tolerances
of
20.0
ppm
for
citrus,
dried
pulp
and
40.0
ppm
for
citrus,
oil.

Meat,
Milk,
Poultry
and
Eggs
The
livestock
feed
items
of
regulatory
interest
for
foliage
of
legume
vegetables,
Group
7;
vegetables,
fruiting,
Group
8
(
except
tomato);
and
pea
and
bean,
succulent
and
dried
shelled,
except
soybean,
Subgroups
6B
and
6C
are
cowpea
seed
at
0.05
ppm,
cowpea
hay
and
forage
at
30.0
ppm;
and
soybean,
forage
and
hay,
for
which
the
tolerance
will
be
raised
to
30
ppm.
Since
the
worst
case
cattle
and
swine
diets
using
existing
and
proposed
tolerances
will
not
exceed
the
level
of
the
ruminant
feeding
study
used
to
establish
the
current
tolerances,
no
increase
in
tolerances
for
ruminant
and
swine
commodities
are
required.
None
of
the
commodities
for
which
tolerances
are
proposed
have
poultry
feed
items
of
regulatory
interest,
therefore
no
change
in
azoxystrobin
poultry
tolerances
is
required.

The
citrus
feed
item,
citrus
dried
pulp,
has
already
been
considered
and
found
to
have
no
effect
on
the
MTDB
of
azoxystrobin
for
livestock.
Therefore,
the
currently
established
tolerances
for
secondary
residues
of
azoxystrobin
remain
adequate.

Confined/
Field
Accumulation
in
Rotational
Crops
Adequate
confined
studies
have
previously
been
reviewed.
Several
conjugated
metabolites
of
primary
crop
metabolites
were
identified,
indicating
that
azoxystrobin
is
more
Page
28
of
52
extensively
metabolized
in
rotational
crops
than
in
primary
crops.
The
residues
of
concern
in
rotational
crops
are
parent
and
the
Z­
isomer.

Limited
field
rotational
crop
studies
were
previously
reviewed.
The
limited
field
accumulation
study
is
adequate
to
indicate
that
residues
of
azoxystrobin
and
Z­
isomer
will
not
occur
in
mustard
greens,
turnip
roots,
turnip
tops,
and
wheat
grain
planted
36
days
after
application
of
azoxystrobin.
This
study
also
indicates
that
small
residues
of
azoxystrobin
per
se
may
occur
in
wheat
matrices
other
than
grain
at
a
plantback
interval
of
approximately
60
days
after
treatment.
No
residues
of
Z­
isomer
were
found
in
any
matrix
at
any
plantback
interval.
The
label
indicates
that
only
crops
with
registered
uses
may
be
planted
within
12
months
of
application.
This
plantback
interval
is
adequate.

4.2.2
Dietary
Analysis
Acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEMFCID
 
,
Version
2.03),
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
1994­
96,
and
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
For
chronic
exposure
assessment,
consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups,
but
for
acute
exposure
assessment
are
retained
as
individual
consumption
events.
Based
on
analysis
of
the
1994­
96,
and
98
CSFII
consumption
data,
which
took
into
account
dietary
patterns
and
survey
respondents,
HED
concluded
that
it
is
most
appropriate
to
report
risk
for
the
following
population
subgroups:
the
general
U.
S.
population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
adults
20­
49,
females
13­
49,
and
adults
50+
years
old.

Established
and
recommended
tolerances
were
used
in
acute
and
chronic
dietary
assessments.
Percent
crop
treated
data
were
not
applied.
DEEM
 
default
concentration
factors
were
used
except
for
tomato
juice,
puree,
paste
and
catsup.
Processing
data
show
no
concentration
in
these
fractions;
the
values
were
set
at
one.

4.2.2.1
Acute
Dietary
The
acute
dietary
exposure
analysis
for
azoxystrobin
is
a
Tier
1
assessment
because
no
additional
data
were
used
to
refine
the
analysis.
One
hundred
percent
of
proposed
and
registered
crops
are
assumed
treated
with
azoxystrobin
(
100%
CT)
and
tolerance­
level
residues
were
used
in
the
analysis.
The
acute
dietary
endpoint
applies
to
all
population
subgroups
including
infants
and
children.
The
highest
estimate
for
acute
drinking
water
exposure,
170
ppb,
was
used
in
the
analysis
(
see
Section
4.3,
below).
The
dietary
exposure
estimates
for
the
U.
S.
population
at
27%
of
the
aPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
at
74%
of
the
aPAD,
do
not
exceed
HED's
level
of
concern.
Page
29
of
52
TABLE
4.2.2.1
Results
of
Acute
Dietary
Exposure
Analysis
95th
Percentile
Population
Subgroup
aPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
aPAD
General
U.
S.
Population
0.67
0.183066
27
All
Infants
(<
1
year
old)
0.67
0.157206
24
Children
1­
2
years
old
0.67
0.496490
74
Children
3­
5
years
old
0.67
0.373851
56
Children
6­
12
years
old
0.67
0.241694
36
Youth
13­
19
years
old
0.67
0.185218
28
Adults
20­
49
years
old
0.67
0.151215
23
Adults
50+
years
old
0.67
0.138010
21
Females
13­
49
years
old
0.67
0.159688
24
Page
30
of
52
4.2.2.2
Chronic
Dietary
The
chronic
dietary
exposure
analysis
for
azoxystrobin
is
a
Tier
2
analysis:
tolerancelevel
residues
and
some
%
CT
were
used
in
the
analysis.
The
chronic
dietary
endpoint
applies
to
all
population
subgroups
including
infants
and
children.
The
highest
estimate
for
chronic
drinking
water
exposure,
33
ppb,
was
used
in
the
analysis
(
see
Section
4.3,
below).

The
dietary
exposure
estimate
for
the
U.
S.
population
was
8%
of
the
cPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
was
21%
of
the
cPAD.
Risk
estimates
for
all
population
subgroups
are
below
HED's
level
of
concern
(
100%
of
the
cPAD).

Table
4.2.2.2
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.18
0.013570
8
All
Infants
(<
1
year
old)
0.18
0.010552
6
Children
1­
2
years
old
0.18
0.034658
19
Children
3­
5
years
old
0.18
0.027564
15
Children
6­
12
years
old
0.18
0.017825
10
Youth
13­
19
years
old
0.18
0.011536
6
Adults
20­
49
years
old
0.18
0.011228
6
Adults
50+
years
old
0.18
0.011754
7
Females
13­
49
years
old
0.18
0.011497
6
4.2.2.3
Cancer
Dietary
The
HED
RfD/
Peer
Review
Committee,
in
its
meeting
of
November
7,
1996,
determined
that
azoxystrobin
should
be
classified
as
"
not
likely
to
be
a
human
carcinogen."
Due
to
the
classification,
no
cancer
risk
assessment
was
performed.

4.3
Water
Exposure/
Risk
Pathway
Although
moderately
persistent
in
soils
and
stable
to
hydrolysis,
the
likelihood
of
azoxystrobin
moving
into
ground
and
surface
water
is
low
due
to
high
soil/
water
partitioning
coefficients
and
low
single
application
rates.
The
HED
MARC
determined
that
the
residue
of
Page
31
of
52
concern
in
water
is
azoxystrobin
only
because
the
parent
compound
is
the
most
likely
residue
to
be
found
in
surface
water.

Monitoring
data
are
not
available
to
perform
a
quantitative
drinking
water
risk
assessment
for
azoxystrobin
at
this
time.
EFED
provided
EECs
for
azoxystrobin
based
upon
the
crop
with
the
highest
application
rate
(
turf).
Tier
1
surface
and
ground
water
EECs
were
generated
using
EFED's
FIRST
and
SCI­
GROW
models,
respectively.
As
the
use
of
azoxystrobin
on
turf
has
the
highest
single
and
yearly
application
rate
at
0.55
lb
ai/
A
and
5
lb
ai
/
A/
year,
respectively,
this
application
rate
was
used
in
the
FIRST
and
SCI­
GROW
models
to
estimate
the
concentrations
of
this
chemical
in
surface
and
ground
water,
respectively.
Should
the
yearly
application
rate
on
non­
cropland
change,
or
should
a
use
of
azoxystrobin
with
a
higher
use
rate
be
added,
EFED
may
have
to
revise
the
EECs
accordingly.

Ground
Water
The
SCI­
GROW
screening
model
developed
in
EFED
estimates
potential
ground
water
concentrations
under
hydrologically
vulnerable
conditions.
Based
on
the
highest
use
rate
(
turf
use,
9
applications
per
year,
10­
day
interval,
and
0.55
lb
ai/
A/
application),
the
upper­
bound
concentration
of
azoxystrobin
was
estimated
at
3.1
ppb.
This
value
can
be
used
for
both
acute
and
chronic
risk
assessments.
This
value
represents
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
ground
water
which
result
from
the
use
of
azoxystrobin
on
turf.

Surface
Water
Based
on
the
Tier
I
modeling
results,
azoxystrobin
EECs
in
surface
water
are
not
likely
to
exceed
170
ppb
for
the
acute
(
peak)
concentration
or
33
ppb
for
the
chronic
(
annual
average)
concentration.
These
values
represent
upper­
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
which
result
from
the
use
of
azoxystrobin
on
turf.

4.4
Residential
Exposure/
Risk
Pathway
Azoxystrobin
is
currently
registered
for
use
on
residential
turfgrass
and
ornamentals,
as
well
as
indoor
surfaces.
Short­
term
exposures
may
occur
during
adult
residential
handling
activities.
HED's
Draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments,
and
Recommended
Revisions
(
ExpoSAC
Policy
Number
12,
revised
2/
22/
01),
were
used
as
the
basis
for
all
residential
handler
exposure
calculations.
Some
of
the
handler
exposure
data
used
in
this
assessment
are
from
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF;
the
risk
manager
is
encouraged
to
pursue
data
compensation
in
the
event
the
registrant
is
not
a
member
of
the
task
force).
Non­
occupational
handler
inhalation
MOEs
were
1,700,000
for
mixing,
loading
and
applying
WDG
formulation
to
indoor
surfaces,
and
2,700,000
and
230,000
for
mixing,
loading
and
applying
liquid
formulation
to
turf,
for
spot
application
with
a
low­
pressure
handwand
and
for
broadcasting
with
a
garden
hose­
end
sprayer
to
turf,
respectively.
These
MOEs
are
well
above
the
LOC
for
non­
occupational
handler
scenarios,
and
therefore,
are
not
of
concern.
Page
32
of
52
4.4.1
Home
Uses
Products
containing
azoxystrobin
are
registered
for
application
to
turf,
ornamentals,
and
indoor
carpets/
other
surfaces.
These
products
may
be
applied
to
turf
at
rates
up
to
0.95
lb
ai
per
acre,
5
times
per
year
(
not
to
exceed
5
lb
ai/
A/
yr),
to
ornamentals
at
rates
up
to
0.75
lb
ai
per
acre,
every
7
to
14
days
(
not
to
exceed
5
lb
ai/
A/
yr),
and
indoors
to
carpets/
other
surfaces
at
rates
up
to
3.3E­
5
lb
ai/
ft2,
every
3
months
as
needed
(
not
to
exceed
4
times
per
year).

Residential
handlers
may
receive
short­
term
dermal
and
inhalation
exposure
to
azoxystrobin
when
mixing,
loading
and
applying
the
formulations.
Adults
and
children
may
be
exposed
to
azoxystrobin
residues
from
dermal
contact
with
foliage/
surfaces
during
postapplication
activities.
Toddlers
may
receive
short­
and
intermediate­
term
oral
exposure
from
incidental
ingestion
during
postapplication
activities.

As
no
dermal
endpoint
was
selected
by
the
HIARC,
a
dermal
exposure
and
risk
assessment
was
not
conducted
for
residential
handlers
or
postapplication
activities.
NOAELs
of
25
mg/
kg/
day
and
20
mg/
kg/
day
from
oral
toxicity
studies
were
selected
by
the
HIARC
for
assessing
the
risk
from
short­
and
intermediate­
term
incidental
oral
exposures,
respectively.
These
same
NOAELs
were
selected
by
the
HIARC
for
assessing
the
risks
from
short­
and
intermediate­
term
inhalation
exposures,
assuming
a
100%
absorption
factor.
The
HED
FQPA
Safety
Factor
Committee
met
on
August
24,
1998,
and
decided
to
reduce
the
10X
safety
factor
to
1X
for
the
U.
S.
population
and
all
population
subgroups
and
for
all
exposure
scenarios.
Thus,
the
LOC
for
risk
assessment
purposes
are
MOEs
of
100
or
less.

No
chemical­
specific
exposure
or
residue
dissipation
data
for
handler
or
postapplication
activities
were
submitted
to
HED
in
support
of
the
registered
lawn
uses
or
indoor
carpet/
other
surfaces
uses.
HED's
Draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments,
and
Recommended
Revisions
(
HED
Policy
Number
12,
revised
2/
22/
01),
were
used
as
the
basis
for
all
residential
handler
exposure
calculations.
Some
of
the
handler
exposure
data
used
in
this
assessment
are
from
the
ORETF
(
the
risk
manager
is
encouraged
to
pursue
data
compensation
in
the
event
the
registrant
is
not
a
member
of
the
task
force).
The
ORETF
data
were
designed
to
replace
the
present
PHED
data
with
higher­
confidence,
higher
quality
data
that
contain
more
replicates
than
the
PHED
data
for
those
scenarios.

4.4.2
Residential
Handler
Exposure
and
Risk
Indoor
Carpet
and
Other
Surfaces
Although
the
currently
registered
label
for
use
on
indoor
carpets/
other
surfaces
prohibits
non­
commercial
applicators
from
mixing,
loading
and
applying
azoxystrobin,
the
label
amendment
for
the
Heritage
®
Fungicide
label
does
not.
Furthermore,
the
currently
registered
label
for
use
on
indoor
carpets/
other
surfaces
specifies
use
restrictions,
whereas
the
Heritage
®
Fungicide
label
does
not.
Therefore,
inhalation
daily
doses
for
residential
handlers
were
calculated
for
the
WDG
formulation
using
data
for
mixing,
loading
and
applying
a
liquid.
Based
Page
33
of
52
on
PHED
unit
exposure
values
from
other
handler
scenarios
with
these
formulation
types,
the
exposure
from
a
WDG
is
expected
to
be
less
than
that
of
handling
a
liquid.
The
open
mixing,
loading,
and
applying
liquid
using
a
low
pressure
handwand
(
PHED)
handler
scenario
was
evaluated.

The
following
assumptions
(
which
include
HED
standard
values)
were
used
to
calculate
inhalation
exposures:

*
The
maximum
application
rate
from
Heritage
®
Fungicide
(
EPA
Reg
No
100­
1093)
of
3.4E­
5
lb
ai/
ft2:

0.5
lb
ai
x
8.34
lb
product
x
1
gal
product
x
0.26
fl.
oz
x
1
gal
tank
mix
lb
product
gal
product
128
fl.
oz.
product
gal
tank
mix
250
ft2
[
assume
density
of
water]

*
Handlers
were
assumed
to
be
using
a
low­
pressure
handwand
for
spot
or
broadcast
treatments
to
1,000
ft2
areas
indoors,
once
per
day.
*
The
inhalation
unit
exposure
for
the
low­
pressure
handwand
is
30

g/
lb
ai
handled
(
from
Appendix
B
of
the
1997
Draft
SOPs
for
Residential
Exposure
Assessments).
*
Residential
handler
body
weight
is
70
kg.
*
The
overall
estimate
of
inhalation
exposure
represents
a
central
to
high­
end
value.

As
shown
in
Table
4.4.2,
the
inhalation
MOE
for
residential
handlers
applying
azoxystrobin
indoors
is
well
above
the
LOC
of
an
MOE
of
100
or
less.

TABLE
4.4.2.
a
Handler
Exposure
and
Risk
Estimates
for
Residential
Indoor
Surface
Applicators
Handler
Scenario
Rate
(
lb
ai/
ft2)
Area
Treated
(
ft2/
day)
PHED
Unit
Exposure1
(
mg/
lb
ai)
Short­
term
Daily
Inh.
Dose
2
(
mg/
kg/
day)
Short­
term
Inhalation
MOE
3
Open
Mixing,
Loading,
and
Applying
Liquid
using
a
Low
Pressure
Handwand
3.4E­
5
1000
0.03
1.5E­
5
1,700,000
1
Data
Confidence
for
inhalation
unit
exposures:
low­
pressure
handwand:
80
replicates,
ABC
grade,
medium
confidence
2
Daily
Dose
=
[
Rate
(
lb
ai/
ft2)
x
Area
Treated
(
ft2/
day)
x
Unit
Exposure#
(
mg/
lb
ai
handled)]
/
Body
Weight
(
70
Kg)
3
MOE
=
NOAEL
(
25
mg/
kg/
day)
/
Daily
Inhalation
Dose
(
mg/
kg/
day)

Although
there
is
a
potential
for
residential
bystander
exposure,
the
exposure
scenario
is
not
assessed
for
the
following
reasons:
the
label
specifically
restricts
humans
(
other
than
the
applicator)
and
domestic
animals
from
being
present
while
applications
are
being
made,
until
after
the
application
has
dried;
and
bystander
exposure
is
expected
to
be
less
than
applicator
exposure,
and
the
MOEs
for
the
applicator
exposure
scenario
are
high,
indicating
bystanders
would
be
subject
to
even
less
exposure
and
risk.
Page
34
of
52
Turf
and
Ornamentals
The
currently
registered
labels
for
turf
and
ornamentals
do
not
prohibit
non­
commercial
applicators
from
mixing,
loading
and
applying
either
the
liquid
or
the
WDG
formulations.
The
residential
exposure
and
risk
assessment
for
turf
and
ornamentals
was
conducted
using
the
application
rate
for
turf
because
it
is
the
highest
use
rate.
Inhalation
daily
doses
for
residential
handlers
were
calculated
for
the
flowable
concentrate
formulation
using
data
for
mixing,
loading
and
applying
a
liquid.
Appropriate
data
are
not
available
for
handling
the
WDG
formulation
for
this
use,
however,
based
on
PHED
unit
exposure
values
from
other
handler
scenarios
with
these
formulation
types,
the
exposure
is
expected
to
be
less
than
that
of
handling
a
liquid.
The
following
handler
scenarios
were
evaluated:

1.
mix,
load
and
spot
application
of
liquid
formulation
(
low­
pressure
hand
sprayer),
and
2.
mix,
load
and
broadcast
application
of
liquid
formulation
(
garden
hose­
end
sprayer)

The
following
assumptions
(
which
include
HED
standard
values)
were
used
to
calculate
inhalation
exposures:

*
The
maximum
application
rate
from
Abound
®
Flowable
(
EPA
Reg
No.
10182­
415)
of
1.35
fluid
ounces
of
product
(@
2.08
lb
ai/
Gal)
per
1,000
square
feet
or
0.95
lb
ai
per
acre
was
assumed.
*
Handlers
were
assumed
to
be
using
a
low­
pressure
hand
sprayer
for
spot
treatments
to
1,000
ft2
areas,
or
a
garden
hose­
end
sprayer
for
broadcast
to
a
0.5
acre
lawn.
*
The
inhalation
unit
exposure
for
the
low­
pressure
hand
sprayer
is
30
Fg/
lb
ai
handled
(
from
Appendix
B
of
the
1997
Draft
SOPs
for
Residential
Exposure
Assessments),
and
for
and
garden
hose­
end
sprayer
is
16
Fg/
lb
ai
handled
(
from
ORETF
data).
*
Residential
handler
body
weight
is
70
kg.
*
The
overall
estimate
of
inhalation
exposure
represents
a
central
to
high­
end
value.

As
shown
in
Table
4.2.2.
b,
the
inhalation
MOEs
for
residential
handlers
are
well
above
the
LOC
of
an
MOE
of
100
or
below.

TABLE
4.4.2.
b
Handler
Exposure
and
Risk
Estimates
for
Residential
Lawn
Applicators
Handler
Scenario
Rate
(
lb
ai/
acre)
Acres
Treated
(
acres/
day)
PHED/
ORETF
Unit
Exposure1
(
mg/
lb
ai)
Short­
term
Daily
Inh.
Dose
2
(
mg/
kg/
day)
Short­
term
Inhalation
MOE
3
1.
mix/
load
and
spot
application
of
liquid
formulation
(
low­
pressure
hand
sprayer)
0.95
0.023
0.030
9.4E­
06
2,700,000
2.
mix/
load
and
broadcast
application
of
liquid
formulation
(
garden
hose­
end
sprayer)
0.95
0.5
0.016
1.1E­
04
230,000
Page
35
of
52
1
Data
Confidence
for
inhalation
unit
exposures:
low­
pressure
hand
sprayer:
80
replicates,
ABC
grade,
medium
confidence
garden
hose­
end
sprayer:
30
replicates,
A
grade,
high
confidence
2
Daily
Dose
=
[
Rate
(
lb
ai/
A)
x
Acres
Treated
(
A/
day)
x
Unit
Exposure#
(
mg/
lb
ai
handled)]
/
Body
Weight
(
70
kg)
3
MOE
=
NOAEL
(
25
mg/
kg/
day)
/
Daily
Inhalation
Dose
(
mg/
kg/
day)

4.4.3
Residential
Postapplication
Exposure
and
Risk
Indoor
Carpet
and
Other
Surfaces
Commercial
and
residential
applicators
(
when
formulation
and
application
rates
are
the
same)
deposit
the
same
amount
of
residue
on
the
treated
site.
The
residential
postapplication
scenario
for
use
of
azoxystrobin
on
indoor
carpets
and
other
surfaces
has
been
recently
assessed
in
an
Antimicrobial
Division
(
AD)
memorandum
(
DP
Num:
299065,
D.
Aviado,
7/
2/
04).
Both
the
Heritage
®
Fungicide
label
and
the
formulation
assessed
in
the
AD
memorandum
(
2.08
SC)
call
for
a
liquid
spray
to
indoor
surfaces,
and
both
have
similar
application
rates
(
2.08
SC:
3.3E­
5
lb
ai/
ft2;
Heritage
®
:
3.4E­
5
lb
ai/
ft2).
Considered
together,
the
potential
for
postapplication
exposure
following
application
of
Heritage
is
expected
to
be
quantitatively
and
qualitatively
similar
to
postapplication
exposure
following
application
of
the
2.08
SC
formulation.
However,
because
the
restrictions
on
the
labels
differ,
and
because
AD
and
HED
sometimes
employ
different
assumptions
in
their
exposure
algorithms,
the
residential
postapplication
exposure
scenario
assessment
is
being
conducted
again
in
this
document.

The
following
postapplication
exposure
scenarios
resulting
from
indoor
surface
treatment
were
assessed:

(
1)
toddlers'
incidental
ingestion
of
pesticide
residues
on
hard
indoor
surfaces
from
hand­
to­
mouth
transfer,
and
(
2)
toddlers'
incidental
ingestion
of
pesticide
residues
on
carpet/
textile
indoor
surfaces
from
hand­
to­
mouth
transfer.

The
exposure
and
risk
estimates
for
the
residential
exposure
scenarios
are
assessed
for
the
day
of
application
(
day
"
0")
because
it
is
assumed
that
toddlers
could
contact
the
indoor
surface
immediately
after
the
application
has
dried.
Both
short­
and
intermediate­
term
exposure
is
expected.
The
equation
used
for
the
exposure
calculations
are
presented
below
and
the
results
are
presented
in
Table
4.4.3.
a.

PDRt
for
hand­
to­
mouth
=
ISR
*
SA
*
EX
*
FQ
*
ET
Where:

PDRt
=
potential
dose
rate
on
day
"
t"
(
mg/
day)
ISR
=
AR
*
F
*
(
1­
D)
t
*
CF1
*
CF2
(
mg/
cm2)

and:
AR
=
application
rate
(
lb
ai/
ft2);
3.4E­
5
lb
ai/
ft2
Page
36
of
52
F
=
fraction
of
ai
available
on
vinyl/
hard
surfaces
or
carpet/
textile
surfaces
(
unitless);
10%
and
5%,
respectively
D
=
fraction
of
residue
that
dissipates
daily
(
unitless)
­
not
employed
in
this
assessment
t
=
postapplication
day
on
which
exposure
is
being
assessed
­
assumed
to
be
day
"
0"
in
this
assessment
CF1
=
conversion
factor
(
4.54E+
5
mg/
lb)
CF2
=
conversion
factor
(
1.08E­
3
ft2/
cm2
)

SA
=
surface
area
of
the
hands
(
cm2/
event);
use
palmar
surface
area
of
3
fingers;
20
cm2
EX
=
extraction
from
the
hand
by
saliva
=
50%
FQ
=
frequency
of
hand­
to­
mouth
activity
(
events/
hr);
20
events/
hr
for
short­
term,
9.5
events/
hr
for
intermediate­
term
ET
=
exposure
time
(
hr/
day);
4
hrs/
day
for
vinyl/
hard
surfaces;
8
hrs/
day
for
carpet/
textile
surfaces
and:
PDRt­
norm
=
PDRt
/
BW
(
15
kg);
potential
dose
rate,
normalized
to
body
weight,
on
day
"
t"
(
mg/
kg/
day)
MOE
=
NOAEL
/
PDRt­
norm;
(
NOAELoral
=
25
mg/
kg/
day
(
short­
term),
20
mg/
kg/
day
(
intermediate­
term)

TABLE
4.4.3.
a
Short­
and
Intermediate­
Term
Incidental
Ingestion
Exposure
and
Risk
from
Treated
Indoor
Surfaces
Scenarios
ISR
(
mg/
cm2)
Short­
Term
PDR0­
norm
(
mg/
kg/
day)
Int­
Term
PDR0­
norm
(
mg/
kg/
day)
Short­
Term
MOE
Int­
term
MOE*

(
1)
Hand­
to­
Mouth
(
vinyl/
hard
surfaces)
1.7E­
3
0.089
0.042
280
480
(
2)
Hand­
to­
Mouth
(
carpet/
textile
surfaces)
8.34E­
4
0.089
0.042
280
480
*
Although
the
intermediate­
term
MOEs
are
higher
than
the
short­
term
MOEs,
one
should
not
assume
that
it
is
safer
to
be
exposed
for
a
longer
duration.
It
is
an
artifact
of
dose
spacing
in
toxicity
studies,
and
conservative
exposure
assumptions.

These
exposure
and
risk
estimates
are
considered
conservative
because
they
are
based
on
the
residue
available
on
day
"
0",
upper
percentile
values
(
exposure
duration,
S­
T
hand­
to­
mouth
events/
hr)
and
conservative
assumptions
(
total
replenishment
after
each
hand­
to­
mouth
event,
surface
area
mouthed,
and
%
application
rate
available
as
residue).
Although
the
turf
postapplication
scenario
(
assessed
previously
and
reported
below)
involves
three
exposure
pathways,
even
when
they
are
combined,
they
pose
less
risk
than
via
the
indoor
surfaces
Page
37
of
52
postapplication
pathway.
Outdoor
and
indoor
postapplication
exposure
estimates
are
not
combined,
because
co­
occurrence
is
considered
unlikely,
and
would
compound
already
conservative
assumptions.

Turf
and
Ornamentals
The
following
postapplication
exposure
scenarios
resulting
from
lawn
treatment
were
assessed:

(
1)
toddlers'
incidental
ingestion
of
pesticide
residues
on
lawns
from
hand­
to­
mouth
transfer,
(
2)
object­
to­
mouth
transfer
from
mouthing
of
pesticide­
treated
turfgrass,
and
(
3)
incidental
ingestion
of
soil
from
pesticide­
treated
residential
areas.

Postapplication
exposures
from
various
activities
following
lawn
treatment
are
considered
to
be
the
most
common
and
significant
in
residential
settings.
The
exposure
via
incidental
ingestion
of
other
plant
material
may
occur
but
is
considered
negligible.
The
exposure
and
risk
estimates
for
the
residential
exposure
scenarios
are
assessed
for
the
day
of
application
(
day
"
0")
because
it
is
assumed
that
toddlers
could
contact
the
lawn
immediately
after
application.
The
equations
used
for
the
exposure
calculations
are
presented
below
and
the
results
are
presented
in
Table
4.3.3.
b.

PDRt
for
hand­
to­
mouth
=
TTRt
*
SA
*
EX
*
FQ
*
ET
*
CF1
PDRt
for
object­
to­
mouth
(
turfgrass)
=
GRt
*
IgR1
*
CF1
PDRt
for
soil
ingestion
=
SRt
*
IgR2
*
CF1
Where:
PDRt
=
potential
dose
rate
on
day
"
t"
(
mg/
day)
TTRt
=
AR
*
F
*
(
1­
D)
t
*
CF2
*
CF3
GRt
=
AR
*
F
*
(
1­
D)
t
*
CF2
*
CF3
SRt
=
AR
*
F
*
(
1­
D)
t
*
CF2
*
CF3
*
CF4
Where:
TTRt
=
turf
transferrable
residue
on
day
"
t"
(
µ
g
/
cm2
turf)
SA
=
surface
area
of
the
hands
(
cm2/
event);
use
palmar
surface
area
of
3
fingers;
20
cm2
EX
=
extraction
from
the
hand
by
saliva
=
50%
FQ
=
frequency
of
hand­
to­
mouth
activity
(
events/
hr);
20
events/
hr
for
shortterm
9.5
events/
hr
for
intermediate­
term
ET
=
exposure
time
(
hr/
day);
2
hrs/
day
CF1
=
conversion
factor
(
0.001
mg/
µ
g
for
the
TTR
or
GR
equation,
or
1E­
6
g/
µ
g
in
the
SR
equation)
GRt
=
grass
(
and
plant
matter)
residue
on
day
"
t"
(
µ
g
/
cm2)
IgR1
=
mouthing
rate
of
grass
(
cm2/
day);
25
cm2/
day
SRt
=
soil
residue
on
day
"
t"
(
µ
g
/
g)
Page
38
of
52
IgR2
=
ingestion
rate
of
soil
(
mg/
day);
100
mg/
day
AR
=
application
rate
(
lb
ai/
acre);
0.95
lb
ai/
acre
F
=
fraction
of
ai
available
on
turf/
grass
or
in
uppermost
cm
of
soil
(
unitless);
5%
and
20%
on
turf/
grass
for
hand­
to­
mouth
and
object­
to­
mouth,
respectively,
and
100%
in
uppermost
1
cm
of
soil
D
=
fraction
of
residue
that
dissipates
daily
(
unitless);
10%
t
=
postapplication
day
on
which
exposure
is
being
assessed
CF2
=
conversion
factor
(
4.54E+
8
µ
g
/
lb)
CF3
=
conversion
factor
(
2.47E­
8
acre/
cm2
)
CF4
=
conversion
factor
(
0.67
cm3/
g
soil)
and
PDRt­
norm
=
PDRt
/
BW
MOE
=
NOAEL
/
PDRt­
norm
Where:
PDRt­
norm
=
potential
dose
rate,
normalized
to
body
weight,
on
day
"
t"
(
mg/
kg/
day)
BW
=
body
weight
(
kg);
15
kg
NOAELoral
=
25
mg/
kg/
day
(
short­
term),
20
mg/
kg/
day
(
intermediate­
term)

TABLE
4.4.3.
b.
Short­
and
Intermediate­
Term
Incidental
Ingestion
Exposure
and
Risk
from
Treated
Turf
Scenarios
TTR/
GR/
SR0
(
µ
g
/
cm2
or
g)
Short­
Term
PDR0­
norm
(
mg/
kg/
day)
Int­
Term
PDR0­
norm
(
mg/
kg/
day)
Short­
Term
MOE
Int­
term
MOE*

(
1)
Hand­
to­
Mouth
0.53
0.014
0.0067
1,800
3,000
(
2)
Mouthing
Grass
2.13
0.0035
0.0035
7,000
5,600
(
3)
Soil
Ingestion
7.1
0.000048
0.000048
530,000
420,000
Combined
N/
A
0.018
0.010
1,400
1,900
*
Although
the
intermediate­
term
MOEs
are
higher
than
the
short­
term
MOEs,
one
should
not
assume
that
it
is
safer
to
be
exposed
for
a
longer
duration.
It
is
an
artifact
of
dose
spacing
in
toxicity
studies,
and
conservative
exposure
assumptions.

Both
short­
term
and
intermediate­
term
MOEs
for
each
scenario,
and
the
combined
MOE
resulting
from
all
three
exposures,
are
above
the
LOC.

The
exposure
estimates
generated
above
are
based
on
some
upper­
percentile
(
i.
e.,
maximum
application
rate,
initial
amount
of
transferrable
residue
and
duration
of
exposure)
and
some
central
tendency
(
i.
e.,
surface
area,
hand­
to­
mouth
activity,
and
body
weight)
assumptions
and
are
considered
to
be
representative
of
high­
end
exposures.
The
uncertainties
associated
with
this
assessment
stem
from
the
use
of
an
assumed
amount
of
pesticide
available
from
turf,
and
assumptions
regarding
transfer
of
chemical
residues
and
hand­
to
mouth
activity.
The
estimated
exposures
are
believed
to
be
reasonable
high­
end
estimates
based
on
observations
from
chemical­
specific
field
studies
and
professional
judgement.
Page
39
of
52
4.4.4
Recreational
Postapplication
Exposure
and
Risk
Recreational
exposures
to
turf
and
indoor
surfaces
are
expected
to
be
similar
to,
or
in
many
cases
less
than,
those
evaluated
in
section
4.4.3
Residential
Postapplication
Exposure
and
Risk;
therefore,
a
separate
recreational
exposure
assessment
was
not
included.
Although
azoxystrobin
may
be
applied
to
golf
courses,
a
risk
assessment
for
the
golfing
scenario
is
not
required
because
no
dermal
endpoint
was
selected
by
the
HIARC.

4.4.5
Off
Target
Non­
Occupational
Exposure
Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
the
ground
application
method
employed
for
azoxystrobin.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
database
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.

Please
note
that
as
indicated
in
this
assessment,
azoxystrobin
is
directly
applied
to
residential
turf
and
does
not
result
in
exposures
of
concern.
It
is
unlikely
that
the
potential
for
risk
of
exposure
to
spray
drift
from
agricultural
uses
would
be
higher
than
that
estimated
for
the
turf
use
of
this
chemical.

5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
5.1
Acute
Aggregate
Risk
(
food
+
drinking
water)

The
aggregate
acute
risk
estimates
include
exposure
to
residues
of
azoxystrobin
in
food
and
water,
and
does
not
include
dermal,
inhalation
or
incidental
oral
exposure.
Since
the
dietary
exposure
assessment
already
includes
the
highest
acute
exposure
from
the
drinking
water
modeling
data,
no
further
calculations
are
necessary.
The
acute
risk
estimate
for
the
U.
S.
population
and
all
other
population
subgroups,
resulting
from
aggregate
exposure
to
azoxystrobin
in
food
and
drinking
water
is
below
HED's
level
of
concern.
The
food
and
water
exposure
estimates
for
the
U.
S.
population
is
27%
of
the
aPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
is
74%
of
the
aPAD.

5.2
Short­
Term
Aggregate
Risk
(
food
+
drinking
water
+
residential)
Page
40
of
52
The
short­
term
aggregate
risk
assessment
estimates
risks
likely
to
result
from
1­
to
30­
day
exposure
to
azoxystrobin
residues
from
food,
drinking
water,
and
residential
pesticide
uses.
High­
end
estimates
of
residential
exposure
are
used
in
the
short­
term
assessment,
while
average
values
are
used
for
food
and
drinking
water
exposure
(
i.
e.
chronic
exposures).

No
endpoint
has
been
selected
for
short­
term
dermal
exposure
to
azoxystrobin;
therefore
it
will
not
be
included
in
this
assessment.
The
same
endpoints
were
identified
by
HIARC
for
short­
term
incidental
oral
and
inhalation
risk
assessment
(
based
on
increased
maternal
diarrhea,
urinary
incontinence,
and
salivation).
Therefore,
this
assessment
will
combine
dietary/
incidental
oral
exposure
with
inhalation
exposure.

A
short­
term
risk
assessment
is
required
for
adults
because
there
is
a
residential
handler
inhalation
exposure
scenario.
In
addition,
a
short­
term
risk
assessment
is
required
for
infants
and
children
because
there
is
a
residential
post­
application
oral
exposure
scenario.
Average
food
and
drinking
water
exposures
are
already
included
in
the
chronic
dietary
exposure
assessment
in
Table
4.2.2.2,
above.
Adult
inhalation
risks
are
summarized
for
indoor
and
outdoor
uses
in
Tables
4.3.3.
a
and
4.3.3.
b,
above.
Toddlers'
incidental
oral
exposure
is
assumed
to
include
hand­
to­
mouth
exposure,
object­
to­
mouth
exposure
and
exposure
through
incidental
ingestion
of
soil.
Incidental
oral
risks
for
children
are
summarized
for
indoor
and
outdoor
uses
in
Tables
4.4.3.
a
and
4.4.3.
b,
above.

TABLE
5.2.
Short­
Term
Aggregate
Risk
(
Food,
Water
and
Incidental
Oral
Exposure)

Short­
Term
Scenario
Population
NOAEL
mg/
kg/
day
LOC
MOE1
Average
Food
+
Water
Exposure
mg/
kg/
day
Residential
Exposure2
mg/
kg/
day
Aggregate
MOE
(
food
and
residential)
3
US
Population
0.013570
0.00011
1800
Youth
(
13­
19
years)
0.011536
0.00011
2150
All
Infants
(<
1
year)
0.010552
0.089
250
Children
(
1­
2
years)
0.034658
0.089
200
Females
(
13­
49
years
old)
25
100
0.011497
0.00011
2150
1
The
level
of
concern
(
LOC)
MOE
is
100,
based
on
inter­
and
intra­
species
safety
factors
totaling
100.
2
Residential
Exposure
=
[
Incidental
Oral
exposure
from
all
possible
sources
or
Inhalation
exposure].
No
residential
oral
exposure
is
expected
for
adults.
3
Aggregate
MOE
=
[
NOAEL
(
25
mg/
kg/
day)
÷
(
Avg
Food
Exposure
+
Residential
Exposure)].
Page
41
of
52
As
shown
above
in
Table
5.2,
the
aggregate
short­
term
MOEs
for
the
US
population
at
1800
and
children
1­
2
years
old
at
250
do
not
exceed
HED's
level
of
concern,
a
MOE
of
100.
TRB
does
not
consider
short­
term
aggregate
risk
for
adults
and
children
to
be
a
concern.

5.3
Intermediate­
Term
Aggregate
Risk
The
intermediate­
term
aggregate
risk
assessment
estimates
risks
likely
to
result
from
one
to
six
months
of
exposure
to
azoxystrobin
residues
from
food,
drinking
water,
and
residential
pesticide
uses.
High­
end
estimates
of
residential
exposure
are
used
in
the
intermediate­
term
assessment,
while
average
values
are
used
for
food
and
drinking
water
exposure
(
i.
e.
chronic
exposures).

No
endpoint
has
been
selected
for
intermediate­
term
dermal
exposure
to
azoxystrobin;
therefore
it
will
not
be
included
in
this
assessment.
The
same
endpoints
were
identified
by
HIARC
for
intermediate­
term
incidental
oral
and
inhalation
risk
assessment
(
based
on
decreased
body
weight
gain
in
both
sexes
and
clinical
signs
indicative
of
reduced
nutrition.
the
basis
for
the
oral
endpoint
is
increased
maternal
diarrhea,
urinary
incontinence,
and
salivation).
Therefore,
this
assessment
will
combine
dietary/
incidental
oral
exposure
with
inhalation
exposure.

An
intermediate­
term
risk
assessment
is
not
required
for
adults
because
intermediate­
term
residential
handler
scenarios
are
not
expected
to
occur.
However,
an
intermediate­
term
risk
assessment
is
required
for
infants
and
children
because
there
is
a
residential
post­
application
oral
exposure
scenario.

TABLE
5.3
Intermediate­
Term
Aggregate
Risk
(
Food,
Water
and
Incidental
Oral
Exposure)

Intermediate­
Term
Scenario
Population
NOAEL
mg/
kg/
day
LOC
MOE1
Average
Food
+
Water
Exposure
mg/
kg/
day
Residential
Exposure2
mg/
kg/
day
Aggregate
MOE
(
food
and
residential)
3
Children
(
1­
2
years)
20
100
0.034658
0.042
260
1
The
level
of
concern
(
LOC)
MOE
is
100,
based
on
inter­
and
intra­
species
safety
factors
totaling
100.
2
Residential
Exposure
=
[
Incidental
Oral
exposure
from
all
possible
sources
+
Inhalation
exposure].
No
residential
oral
exposure
is
expected
for
adults.
3
Aggregate
MOE
=
[
NOAEL
(
20
mg/
kg/
day)
÷
(
Avg
Food
Exposure
+
Residential
Exposure)].

As
shown
above
in
Table
5.3,
the
aggregate
intermediate­
term
MOEs
for
children
1­
2
years
old,
which
is
the
population
subgroup
with
the
highest
exposure,
at
260
do
not
exceed
HED's
level
of
concern,
a
MOE
of
100.
TRB
does
not
consider
intermediate­
term
aggregate
risk
for
adults
and
children
to
be
a
concern.

5.4
Chronic
Aggregate
Risk
The
aggregate
chronic
risk
assessment
takes
into
account
average
exposure
estimates
from
dietary
consumption
of
azoxystrobin
(
food
and
drinking
water)
and
residential
uses.
Since
the
exposure
from
all
the
residential
uses
is
considered
short­
term,
the
aggregate
chronic
assessment
included
food
Page
42
of
52
and
drinking
water
only.
Since
the
dietary
exposure
assessment
already
includes
the
highest
chronic
exposure
from
the
drinking
water
modeling
data,
no
further
calculations
are
necessary.
The
general
U.
S.
population
and
all
population
subgroups
have
exposure
and
risk
estimates
which
are
below
HED's
level
of
concern
(
i.
e.,
the
percentages
of
the
chronic
population
adjusted
doses
(
cPADs)
are
all
below
100%).
The
exposure
to
the
U.
S.
population
was
8%
of
the
cPAD
and
the
most
highly
exposed
subgroup,
children
1­
2
yrs
old,
at
19%
of
the
cPAD.
Therefore,
chronic
risk
estimates
resulting
from
aggregate
exposure
to
azoxystrobin
in
food
and
drinking
water
are
below
HED's
level
of
concern
from
all
population
subgroups.

5.5
Cancer
Aggregate
Risk
The
HED
RfD/
Peer
Review
Committee,
in
its
meeting
of
November
7,
1996,
determined
that
azoxystrobin
should
be
classified
as
"
not
likely
to
be
a
human
carcinogen."
Due
to
the
classification,
no
cancer
risk
assessment
was
performed.

6.0
CUMULATIVE
RISK
The
Food
Quality
Protection
Act
(
1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
tolerance
action
for
azoxystrobin,
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
azoxystrobin.
For
purposes
of
this
tolerance
action,
EPA
has
assumed
that
azoxystrobin
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.

7.0
OCCUPATIONAL
EXPOSURE
Workers
may
be
exposed
to
azoxystrobin
during
mixing,
loading,
application,
and
postapplication
activities.
Based
on
the
proposed
use
pattern,
short­,
and
intermediate­
term
exposures
may
occur.
Chronic
exposures
(
more
than
6
months
of
continuous
exposure)
are
not
expected.

7.1
Occupational
Handler
Handlers
are
assumed
to
have
potential
short­
(
1­
30
consecutive
days)
and
intermediate­
term
(
31­
180
consecutive
days)
dermal
and
inhalation
exposure
to
azoxystrobin.
However,
potential
Page
43
of
52
intermediate­
term
exposure
is
less
likely
due
to
the
use
directions
for
azoxystrobin
formulations
(
which
involve
restrictions
on
sequential
azoxystrobin/
strobilurin­
fungicide
formulation
applications,
specific
inter­
application
intervals,
and
number
of
applications
per
season).
Long­
term
handler
exposure
is
not
expected
via
any
route.

As
previously
stated,
there
is
no
hazard
via
the
dermal
route,
therefore,
only
risk
via
the
inhalation
route
is
considered
in
this
document.
The
short­
term
inhalation
toxicity
endpoint
is
based
on
increased
maternal
diarrhea,
urinary
incontinence,
and
salivation
seen
in
the
rat
prenatal
developmental
oral
toxicity
study
at
the
LOAEL
of
100
mg/
kg/
day
(
NOAEL
=
25
mg/
kg/
day).
The
intermediate­
term
inhalation
toxicity
endpoint
is
based
on
decreased
body
weight
gain
in
both
sexes
and
clinical
signs
indicative
of
reduced
nutrition
in
the
rat
90­
day
feeding
study
at
the
LOAEL
of
211/
223
mg/
kg/
day
in
males/
females
(
LOAEL
=
20
mg/
kg/
day).
Daily
doses
were
calculated
assuming
a
70
kg
body
weight
for
adults
(
because
the
toxicity
endpoints
are
not
gender­
specific)
and
a
100%
inhalation
absorption
factor.

No
chemical­
specific
handler
exposure
data
were
submitted
in
support
of
this
action
to
inform
daily
dose
calculations.
It
is
the
policy
of
HED
to
use
data
from
PHED
Version
1.1
as
presented
in
the
PHED
Surrogate
Exposure
Guide
(
8/
98)
to
assess
handler
exposures
for
regulatory
actions
when
chemical­
specific
monitoring
data
are
not
available
(
HED
Science
Advisory
Council
for
Exposure
[
ExpoSAC]
Draft
Policy
#
7,
dated
1/
28/
99).
Proprietary
data
from
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
have
also
been
used
in
this
assessment.
The
ORETF
data
were
designed
to
replace
the
present
PHED
data
with
higher­
confidence,
higher
quality
data
that
contain
more
replicates
than
the
PHED
data
for
particular
scenarios
(
the
risk
manager
is
encouraged
to
pursue
data
compensation
in
the
event
the
registrant
is
not
a
member
of
the
task
force).
Additionally,
typical
HED
standard
values
were
used
for
the
amount
treated
per
day
(
ExpoSAC
Policy
#
9,
dated
7/
5/
00).

The
daily
doses
presented
in
this
assessment
are
characterized
as
mid­
to
high­
end
exposure
estimates
because
both
conservative
and
average
values
were
used
in
the
calculations:
the
unit
exposure
values
from
PHED
are
considered
to
be
central
tendency;
the
areas
treated
per
day
values
are
considered
typical­
to­
high­
end;
the
application
rates
and
other
treatment
variables
used
in
this
assessment
are
upper
percentile
values;
and
the
inhalation
absorption
factor
and
body
weight
values
are
considered
conservative.

Agricultural
Crops
For
the
proposed
uses
on
agricultural
crops,
the
scenarios
assessed
in
this
document
are
the
following
(
the
source
of
the
unit
exposure
values
used
for
each
scenario
is
in
parenthesis):

(
1)
Open
Mixing/
Loading
Liquids
for
Aerial
Application
and
Chemigation
(
PHED)
(
2)
Open
Mixing/
Loading
Liquids
for
Groundboom
(
PHED)
(
3)
Open
Mixing/
Loading
Dry
Flowable
for
Aerial
Application
and
Chemigation
(
PHED)
(
4)
Open
Mixing/
Loading
Dry
Flowable
for
Groundboom
(
PHED)
(
5)
Application
of
Liquid
using
Aerial­
Fixed
Wing,
Enclosed
Cockpit
(
PHED)
(
6)
Flagging
for
Aerial
Liquid
Application
(
PHED)
Page
44
of
52
(
7)
Application
of
Liquid
using
Groundboom
(
PHED)
dd
Greenhouse
Roses
For
greenhouse
roses,
the
scenarios
assessed
in
this
document
are
the
following
(
the
source
of
the
unit
exposure
values
used
for
each
scenario
is
in
parenthesis):
(
1)
Open
Mixing/
Loading
Liquid
for
a
High
Pressure
Handwand
(
PHED)
(
2)
Application
of
Liquid
using
a
High
Pressure
Handwand
(
PHED)
(
3)
Open
Mixing/
Loading
Liquid
for,
and
Applying
Liquid
using,
a
Backpack
Sprayer
(
PHED)
(
4)
Open
Mixing/
Loading
Liquid
for,
and
Applying
Liquid
using,
a
Low
Pressure
Handwand
(
PHED)
(
5)
Open
Mixing/
Loading
Liquid
for,
and
Applying
Liquid
using,
a
High
Pressure
Handwand
(
PHED)
(
6)
Open
Mixing/
Loading
Emulsifiable
Concentrate
for,
and
Applying
Liquid
using,
a
Low
Pressure
Handwand
(
ORETF,
HO,
garden/
ornamental,
MRID
445185­
01,
ExpoSAC
Memorandum,
dated
3/
5/
03)

The
azoxystrobin
formulation
proposed
for
use
on
greenhouse
roses
also
contains
the
ai
cyproconazole.
Exposure
to
cyproconazole
resulting
from
use
of
A12910C
on
greenhouse
roses
was
assessed
in
an
HED
memorandum
(
DP
Num:
313833,
M.
Dow,
8/
25/
05),
in
which
scenarios
1
through
4
listed
above
were
used
to
assess
handler
exposure.
This
document
focuses
on
azoxystrobin.
Scenarios
5
and
6
were
included
in
this
document
to
further
characterize
the
greenhouse
roses
use,
and
to
provide
more
refined
exposure
estimates,
using
data
of
higher
quality.

The
A12910C
Fungicide
label
indicates
"
all
types
of
spray
equipment
[
can
be]
used
for
making
greenhouse
applications."
When
handlers
are
using
low
pressure
handwands
and
backpack
sprayers,
HED
typically
assumes
40
gal/
day
are
used;
and
when
handlers
are
using
high
pressure
handwands,
HED
typically
assumes
1000
gal/
day
are
used.
However,
the
A12910C
label
does
not
specify
the
desired
concentration
of
the
tank
mix,
which
makes
it
difficult
to
employ
the
gal/
day
standard
values.
For
handgun
sprayers,
HED
typically
assumes
five
acres
[
A]/
day
are
treated,
a
value
more
easily
employed
with
the
fl
oz./
A
application
rate
provided
in
the
A12910C
Fungicide
label.
Therefore,
all
greenhouse
roses
handler
scenarios
(
using
different
spray
equipment)
assume
five
A/
day
are
treated.

It
should
be
noted
that
the
cyproconazole
HED
memorandum
assumed
two
A/
day
were
treated
in
the
assessment
of
A12910C
Fungicide
on
greenhouse
roses.
The
memorandum
cited
a
journal
article
(
J.
Stamper
et
al.,
(
1989)
Pesticide
Exposure
to
Greenhouse
Handgunners.
Arch.
Environm.
Contam.
Toxicol.
18:
515­
529)
that
found
occupational
pesticide
handlers
can
treat
up
to
approximately
two
acres
of
greenhouse
area,
and
the
reviewer
noted
that
even
if
greenhouses
are
larger
than
two
acres,
it
is
unlikely
that
all
acres
in
a
greenhouse
operation
would
require
any
given
pesticide
treatment
at
the
same
time
due
to
different
"
crops"
and
"
cultivars"
requiring
different
treatments
at
different
times
in
the
greenhouse.

In
this
assessment
five
A/
day
is
employed
in
calculating
daily
doses
because
ExpoSAC
Policy
#
9,
dated
7/
5/
00
assumes
five
A/
day
for
handgun
sprayers
(
which
the
reviewer
believes
is
an
adequate
proxy
for
other
handheld
spray
equipment),
and
the
9/
15/
05
ExpoSAC
Meeting
Minutes
state
that
the
Page
45
of
52
ExpoSAC
recommends
a
value
of
five
A/
day
for
short­
term
exposure
scenarios
for
nursery
crops.
This
is
be
a
conservative
assumption.

Unlike
for
agricultural
crops,
HED
believes
only
short­
term
exposure
(
1
­
30
days)
would
be
experienced
by
occupational
handlers
for
the
greenhouse
roses
scenarios
related
to
the
use
of
A12910C
because
of
label
restrictions:
only
one
application
may
be
made
without
"
rotating"
to
another
class
of
fungicide.
That
restriction,
coupled
with
azoxystrobin's
low
vapor
pressure,
makes
it
unlikely
that
intermediate­
term
duration
(
1
­
6
months)
exposures
could
occur
(
even
if
pesticide
treatments
are
made
in
different
parts
of
the
operation
at
different
times
depending
on
disease
pressure/
outbreak).

Indoor
Carpet
and
Other
Surfaces
The
Heritage
®
Fungicide
label
amendment
submitted
by
Syngenta
requests
an
indoor
use
on
carpets
by
commercial
applicators
and/
or
residential
applicators
(
communication
between
M.
Schulz
[
Syngenta]
and
B.
O'Keefe/
J.
Bazuin
[
EPA]
10/
10/
05).
The
commercial
applicator
scenario
has
been
recently
assessed
for
Azoxystrobin
Mold
Retardant
2.08
SC
in
the
AD
memorandum:
Proposed
Registration
for
AZOXYSTROBIN
MOLD
RETARDANT
2.08
SC
End­
Use
Product
as
a
New
Indoor,
Non­
Agricultural
Use
Pattern
for
the
Azoxystrobin
Active
Ingredient:
Non­
Dietary
Occupational/
Residential
Exposure
Considerations
(
DP
Num:
299065,
D.
Aviado,
7/
2/
04).

The
AD
memorandum
considers
a
liquid
formulation,
whereas
this
document
considers
a
WDG
formulation.
Appropriate
data
are
not
available
for
handling
the
WDG
formulation
for
this
use
(
mixing,
loading
and
applying
handheld
spray
equipment),
however,
based
on
PHED
unit
exposure
values
from
other
handler
scenarios
with
these
formulation
types,
the
exposure
is
expected
to
be
less
than
that
of
handling
a
liquid.
Other
parameters
that
factor
into
the
daily
dose
calculation,
such
as
use
patterns
(
equipment
types,
area
treated,
etc.)
and
application
rates
(
2.08
SC:
3.3E­
5
lb
ai/
ft2;
Heritage
®
:
3.4E­
5
lb
ai/
ft2)
for
the
two
products
are
similar.
Considered
together,
in
addition
to
the
conservative
nature
of
the
AD
assessment,
estimated
daily
doses
for
commercial
applicators
using
Heritage
are
expected
to
be
quantitatively
and
qualitatively
similar
to
daily
doses
for
commercial
applicators
using
the
2.08
SC
formulation,
and
therefore
the
AD
commercial
applicator
assessment
serves
as
a
surrogate/
proxy
assessment
for
this
label
amendment
(
the
result
of
the
worst
case
scenario
is
reported
in
Table
20).

Section
18
Uses
The
states
of
Florida
and
Tennessee
have
requested
an
emergency
exemption
for
the
use
of
azoxystrobin
(
formulated
with
propiconazole
in
the
emulsifiable
concentrate
[
EC,
liquid]
formulation
QUILT
®
)
on
Crop
Group
6
(
legume
vegetables,
excluding
soybeans)
and
Crop
Group
7
(
foliage
of
legume
vegetables)
to
control
Phakospora
pachyrizi
(
more
commonly
known
as
Asian
Soybean
Rust
or
Australasian
Soybean
Rust).
This
action
is
part
of
a
larger
action
involving
9
end­
use
products
and
5
active
ingredients
(
ai)
aimed
to
provide
protection
to
legume
vegetables
in
the
event
of
a
soybean
rust
outbreak.
The
fungicides
proposed
for
use
on
legumes
in
the
event
of
a
soybean
rust
outbreak
are
tebuconazole,
myclobutanil,
propiconazole,
trifloxystrobin,
and
azoxystrobin.
Although
the
states
of
Florida
and
Tennessee
are
the
only
applicants
in
this
Section
18
request,
they
expect
other
states
will
apply
to
obtain
exemptions,
citing
their
application.
Page
46
of
52
Directions
provided
as
part
of
the
larger
Section
18
action,
propose
a
maximum
of
three
collective
applications
of
approved
Section
18
fungicides,
and
no
more
than
two
applications
are
proposed
for
any
one
given
ai.
The
total
acreage
of
Crop
Group
6
(
excluding
soybeans)
and
7
is
60,002
acres
in
Florida,
26,500
acres
in
Tennessee,
and
6,026,018
acres
in
the
United
States
(
based
on
45
states
that
responded
to
the
applicant's
survey).
It
is
unlikely
that
the
total
acreage
of
these
crops
would
have
to
be
treated,
and
therefore,
these
are
maximum
estimates
of
potential
acreage
treated.

For
azoxystrobin
in
particular,
the
applicants
submitted
a
label
that
proposed
a
maximum
application
rate
of
14
fluid
ounces
(
fl
oz)
of
QUILT
®
(
0.182
lbs.
ai
[
azoxystrobin
and
propiconazole],
0.0678
lbs.
azoxystrobin)
per
acre
(
A),
applied
at
a
maximum
of
3
times
per
season,
with
interapplication
intervals
ranging
from
14
to
21
days
depending
on
disease
pressure
(
maximum
seasonal
application
rate
42
fl
oz.
QUILT
®
)
.
Note
that
this
conflicts
with
the
general
use
directions
provided
for
the
entire
Section
18
application,
which
indicated
a
maximum
of
2
applications
would
be
permitted
with
any
one
active
ingredient.
The
applicants
estimated,
based
on
the
use
of
up
to
two
applications
of
QUILT
®
,
that
362,500
lbs
of
propiconazole
and
azoxystrobin
would
be
used
per
1
million
acres
treated.
Note
again
that
the
estimated
use
of
up
to
2
applications
of
Quilt
®
conflicts
with
the
proposed
3
applications
(
on
the
specific
Section
18
label
addendum),
and
maximum
seasonal
application
rate
of
42
fl
oz/
A;
which
is
equivalent
to
3
applications
at
the
maximum
application
rate
of
14
fl
oz./
A
(
however,
it
corresponds
with
the
general
use
directions
for
the
entire
Section
18).
This
Section
18
addresses
the
active
ingredient
azoxystrobin
only,
propiconazole
(
and
the
other
active
ingredients)
will
be
considered
in
separate
documents.

Summary
Handlers
are
assumed
to
have
potential
short­
(
1­
30
consecutive
days)
and
intermediate­
term
(
31­
180
consecutive
days)
dermal
and
inhalation
exposure
to
azoxystrobin.
However,
potential
intermediateterm
exposure
is
less
likely
due
to
the
use
directions
for
azoxystrobin
formulations
(
which
involve
restrictions
on
sequential
azoxystrobin/
strobilurin­
fungicide
formulation
applications
and
specific
interapplication
intervals).
Long­
term
handler
exposure
is
not
expected
via
any
route.

As
previously
stated,
there
is
no
hazard
via
the
dermal
route,
therefore,
only
risk
via
the
inhalation
route
is
considered
in
this
document.
The
short­
term
inhalation
toxicity
endpoint
is
based
on
increased
maternal
diarrhea,
urinary
incontinence,
and
salivation
seen
in
the
rat
prenatal
developmental
oral
toxicity
study
at
the
LOAEL
of
100
mg/
kg/
day
(
NOAEL
=
25
mg/
kg/
day).
The
intermediate­
term
inhalation
toxicity
endpoint
is
based
on
decreased
body
weight
gain
in
both
sexes
and
clinical
signs
indicative
of
reduced
nutrition
in
the
rat
90­
day
feeding
study
at
the
LOAEL
of
211/
223
mg/
kg/
day
in
males/
females
(
NOAEL
=
20
mg/
kg/
day).
Daily
doses
were
calculated
assuming
a
70
kg
body
weight
for
adults
(
because
the
toxicity
endpoints
are
not
gender­
specific)
and
a
100%
inhalation
absorption
factor.

No
chemical­
specific
handler
exposure
data
were
submitted
in
support
of
this
action
to
inform
daily
dose
calculations.
It
is
the
policy
of
HED
to
use
data
from
PHED
Version
1.1
as
presented
in
the
PHED
Surrogate
Exposure
Guide
(
8/
98)
to
assess
handler
exposures
for
regulatory
actions
when
chemicalspecific
monitoring
data
are
not
available
(
HED
Science
Advisory
Council
for
Exposure
[
ExpoSAC]
Page
47
of
52
Draft
Policy
#
7,
dated
1/
28/
99).
Additionally,
typical
HED
standard
values
were
used
for
the
amount
treated
per
day
(
ExpoSAC
Policy
#
9,
dated
7/
5/
00).

The
daily
doses
presented
in
this
assessment
are
characterized
as
mid­
to
high­
end
exposure
estimates
because
both
conservative
and
average
values
were
used
in
the
calculations:
the
unit
exposure
values
from
PHED
are
considered
to
be
central
tendency;
the
areas
treated
per
day
values
are
considered
typical­
to­
high­
end;
the
application
rates
and
other
treatment
variables
used
in
this
assessment
are
upper
percentile
values;
and
the
inhalation
absorption
factor
and
body
weight
values
are
considered
conservative.

For
the
proposed
uses
on
agricultural
crops,
the
scenarios
assessed
in
this
document
are
the
following
(
the
source
of
the
unit
exposure
values
used
for
each
scenario
is
in
parenthesis):

Typical
Agricultural
Handler
Scenarios:
1.
Open
Mixing/
Loading
Liquids
for
Aerial
Application
and
Chemigation
(
PHED)
2.
Open
Mixing/
Loading
Liquids
for
Groundboom
(
PHED)
3.
Open
Mixing/
Loading
Dry
Flowable
for
Aerial
Application
and
Chemigation
(
PHED)
4.
Open
Mixing/
Loading
Dry
Flowable
for
Groundboom
(
PHED)
5.
Application
of
Liquid
using
Aerial­
Fixed
Wing,
Enclosed
Cockpit
(
PHED)
6.
Flagging
for
Aerial
Liquid
Application
(
PHED)
7.
Application
of
Liquid
using
Groundboom
(
PHED)

Post­
harvest
Handler
Scenarios:
8.
Open
Mixing/
Loading
Liquids
for
post­
harvest
Commodity
Treatment
(
PHED)
a.
High
volume
(
dilute)
applications
b.
Low
volume
(
concentrated)
applications
c.
Dip
applications
9.
Open
Mixing/
Loading
Dry
Flowable
for
post­
harvest
Commodity
Treatment
(
PHED)
a.
High
volume
(
dilute)
applications
b.
Low
volume
(
concentrated)
applications
c.
Dip
applications
The
following
lays
out
the
methodology
employed
by
HED
to
assess
exposure
resulting
from
the
postharvest
citrus
handler
scenario.
HED
determined
that
during
citrus
waxing
and
packing
operations,
the
amount
handled
per
day
can
be
calculated
as
follows:
a
large
operation
can
process
up
to
2,000
boxes
per
hour,
each
weighing
90
lbs;
while
there
are
some
differences
between
products,
a
typical
product
is
applied
at
a
rate
of
212
grams
of
a
98.5
percent
product
in
192.5
gal
of
waxing
solution
(~
0.0024
lb
ai/
gal
of
soln
[
in
this
assessment,
label
specific
solution
concentrations
are
used
in
the
calculations]);
the
material
is
then
applied
at
a
rate
of
1
gallon
per
8,000­
10,000
pounds
of
fruit
(
this
assumption,
as
well
as
label­
specific
information
is
used
in
the
calculations).
If
fresh
solution
is
used
without
recycling,
the
amount
of
material
handled
at
a
facility
would
be:

Amount
mixed
(
lb
ai/
hr)
=
2,000
(
boxes/
hr)
x
90
(
lbs/
box)
x
1/
8,000
(
gal/
lbs
fruit)
x
soln
conc
(
lb
ai/
gal)
 
Solution
concentrations
are
label
specific
in
this
assessment
(
labels
indicate
concentrations
ranging
from
0.0052
 
0.149
lb
ai/
gal
[
Abound]
and
0.013
 
0.37
lb
ai/
gal
[
Amistar])
 
The
number
of
gallons
of
solution
used
per
amount
fruit
treated
(
gal/
lbs
fruit)
are
both
label­
specific
(
when
available,
i.
e.,
for
the
low
volume
[
concentrated]
applications,
which
Page
48
of
52
specifies
250,000
lbs
of
fruit
can
be
treated
per
batch
of
7
to
25
gallons
of
solution
[
1
gal
soln/
36,000
lbs
fruit
was
used
in
the
exposure
estimate
calculations
for
this
exposure
scenario]);
for
the
other
scenarios
(
high
volume
[
dilute]
applications
and
dipping
applications,
1
gal/
8,000
lbs
of
fruit
is
assumed.

Other
assumptions
are
as
follows:
 
A
work
shift
is
assumed
to
be
8
hours/
day
 
An
average
worker
weighs
70
kg
 
The
respiration
rate
during
these
activities
is
1.0
m
³
per
hour
(
light
activity,
NAFTA
Recommendations).
Under
these
conditions
respiratory
exposure
can
usually
be
considered
negligible
(
although
are
calculated
here
to
ensure
HED
is
protective).
 
Dermal
exposure
is
not
considered
because
there
is
no
hazard
via
the
dermal
route.
Respiratory
exposures
were
obtained
from
the
PHED
Surrogate
Guide.
The
inhalation
unit
exposure
estimates
for
mixer/
loaders
wearing
a
single
layer
of
clothing
with
no
gloves
are
0.0012
mg/
lb
ai
(
liquid)
and
0.00077
mg/
lb
ai
(
flowable)
for
the
respiratory
routes.

Respiratory
Exposure
(
mg/
kg/
day)
=
unit
exposure
(
mg/
lb
ai)
x
amount
mixed
(
lb
ai/
hr)
x
8
(
hrs/
day)/
70
kg
The
estimates
of
exposure
resulting
from
these
calculations
should
be
considered
to
be
conservative
for
the
following
reasons;
(
1)
workers
are
not
assumed
to
wear
any
protective
clothing
while
mixing/
loading
the
material
for
post­
harvest
treatments
(
e.
g.,
respirators);
(
2)
the
material
is
not
assumed
to
be
recycled,
in
practice
some
chemicals
are
recycled
3­
5
times
before
new
formulation
is
mixed;
(
3)
the
estimates
are
derived
from
citrus
data,
other
commodities
may
not
have
the
throughput
associated
with
a
large
citrus
packing
plant.

It
should
be
noted
that
this
methodology
was
not
derived
for
dip
application,
a
scenario
for
which
HED
has
no
data;
however,
because
there
is
no
dermal
hazard,
the
post­
harvest
treatment
scenario
is
considered
an
adequate
surrogate
to
assess
inhalation
exposure
for
the
dip
application
scenario.

A
summary
of
the
exposure
and
risk
estimates
for
all
occupational
handlers
is
included
in
Table
5.
All
handler
scenarios
have
MOEs
that
are
well
above
the
LOC
(
which
is
an
MOE
of
less
than
100)
and
therefore,
are
not
of
concern.

Per
the
Worker
Protection
Standard
(
WPS),
the
minimum
level
of
personal
protective
equipment
and
clothing
for
handlers
is
based
on
the
acute
toxicity
of
the
end­
use
product.
RD
is
responsible
for
ensuring
that
PPE
listed
on
the
label
is
in
compliance
with
WPS.
Page
49
of
52
Table
5.
Occupational
Handler
Short­
and
Intermediate­
term
(
S­
and
I­
T)
Inhalation
Exposure
and
Risk
Estimates
Agricultural
Crops
Activity/
Exposure
Scenario1
Max.
Appl.
Rate2
(
lb
ai/
A)
Amount
Treated
per
Day
(
A)/
Crop
Unit
Exposure3
(
mg/
lb
ai)
Data
Confidence
S­
and
I­
T
Daily
Dose4
(
mg/
kg/
day)
S­
T
MOE
5
I­
T
MOE
5
0.25
1200
/
forage,
fodder,

straw
and
hay
grass
and
nongrass
0.0051
4,900
3,900
(
1)
Open
Mixing/
Loading
Liquids
for
Aerial
Application
and
Chemigation*
0.57
350
/
fruiting
vegetables,

legume
vegetables
&

foliage
of
legume
vegetables
0.0034
7,400
5,900
0.25
200
/
forage,
fodder,

straw
and
hay
grass
and
nongrass
0.00086
29,000
23,000
(
2)
Open
Mixing/
Loading
Liquids
for
Groundboom
0.57
80
/
fruiting
vegetables,

legume
vegetables
&

foliage
of
legume
vegetables
0.0012
High
0.00078
32,000
26,000
0.25
1200
/
forage,
fodder,

straw
and
hay
grass
and
nongrass
0.0033
7,600
6,100
(
3)
Open
Mixing/
Loading
Dry
Flowable
for
Aerial
Application
and
Chemigation*
0.54
350
/
fruiting
vegetables,

legume
vegetables
&

foliage
of
legume
vegetables
0.0021
12,000
9,500
0.25
200
/
forage,
fodder,

straw
and
hay
grass
and
nongrass
0.00055
45,000
36,000
(
4)
Open
Mixing/
Loading
Dry
Flowable
for
Groundboom
0.54
80
/
fruiting
vegetables,

legume
vegetables
&

foliage
of
legume
vegetables
0.00077
High
0.00048
52,000
42,000
0.25
1200
/
forage,
fodder,

straw
and
hay
grass
and
nongrass
0.00029
86,000
69,000
(
5)
Application
of
Liquid
using
Aerial­
Fixed
Wing,
Enclosed
Cockpit
0.57
350
/
fruiting
vegetables,

legume
vegetables
&

foliage
of
legume
vegetables
0.000068
Medium
0.00019
130,000
110,000
Page
50
of
52
Table
5.
Occupational
Handler
Short­
and
Intermediate­
term
(
S­
and
I­
T)
Inhalation
Exposure
and
Risk
Estimates
(
6)
Flagging
for
Aerial
Liquid
Application
0.57
350
/
all
crops
0.00035
High
0.0010
25,000
20,000
0.25
200
/
forage,
fodder,

straw
and
hay
grass
and
nongrass
0.00053
47,000
38,000
(
7)
Application
of
Liquid
using
Groundboom
0.57
80
/
fruiting
vegetables,

legume
vegetables
&

foliage
of
legume
vegetables
0.00074
High
0.00048
52,000
42,000
Citrus
post­
harvest
Activity/
Exposure
Scenario1
Solution
Concentration2
(
lb
ai/
gal
soln)
Amount
Treated
per
Day
(
1
gal/
lbs
fruit)
Unit
Exposure3
(
mg/
lb
ai)
Data
Confidence
S­
and
I­
T
Daily
Dose4
(
mg/
kg/
day)
S­
T
MOE5
I­
T
MOE5
(
8a)
Open
Mixing/
Loading
Liquid
for
high
volume
(
dilute)
applications
0.042
1/
8,000
0.0012
High
0.00013
190,000
150,000
(
8b)
Open
Mixing/
Loading
Liquid
for
low
volume
(
concentrated)
applications
0.15
1/
36,000
0.0012
High
0.00010
250,000
200,000
(
8c)
Open
Mixing/
Loading
Liquid
for
dip
applications
0.010
1/
8,000
0.0012
High
0.000031
810,000
650,000
(
9a)
Open
Mixing/
Loading
Dry
Flowable
for
high
volume
(
dilute)
applications
0.10
1/
8,000
0.00077
High
0.00020
130,000
100,000
(
9b)
Open
Mixing/
Loading
Dry
Flowable
for
low
volume
(
concentrated)
applications
0.37
1/
36,000
0.00077
High
0.00016
160,000
120,000
(
9c)
Open
Mixing/
Loading
Dry
Flowable
for
dip
applications
0.026
1/
8,000
0.00077
High
0.000051
490,000
390,000
1
Dry
Flowable
formulation
=
WDG
=
Amistar;
Flowable
formulation
=
Liquid
formulation
=
Abound
2
PHED
unit
exposure
values:
Baseline
(
i.
e.,
no
respirators).

3
Maximum
application
rates
are
used.
All
crops
are
grouped
in
the
amount
of
acres
that
might
be
treated
in
a
day
 
for
foliage
of
legume
vegetables,
the
maximum
application
rate
on
the
label
is
0.25
lb
ai/
A,
however,
because
the
crop
is
grouped
with
fruiting
vegetables
and
legume
vegetables
(
which
have
maximum
application
rates
of
0.57
specified
on
the
labels),
the
highest
rate
is
used,
which
results
in
a
protective
exposure
for
all
crops
considered
in
the
grouping.

4
Daily
Dose
=
[
Application
Rate
(
lb
ai/
acre)
x
Amount
Treated
(
acre)
x
Unit
Exposure
(
mg/
lb
ai
handled)
x
Inhalation
Absorption
Factor
(
100
%)
]/
Body
Weight
(
70kg).
For
agricultural
crops,
both
Sand
I­
term
daily
dose
estimates
are
equivalent
because
exposure
assumptions
and
inputs
are
screening
level/
unrefined;
the
quantitative
hazard
estimates
they
are
compared
to
incorporate
duration,
and
inform
the
S­
and
I­
T
MOEs.
For
citrus
post­
harvest
treatment,
the
following
equation
was
used:
Daily
Dose
=
[
2000
(
boxes/
hr)
x
90
(
lbs/
box)
x
1/
8,000
(
gal/
lbs
fruit)
[
for
low
volume,
label
specifies
36,000
lbs
fruit
treated
per
gal]
x
soln
conc
(
lb
ai/
gal
soln)
x
8
(
hr/
day)
x
Unit
Exposure
(
mg/
lb
ai
handled)]/
Body
Weight
(
70
kg)

5
MOE
=
NOAEL/
Inhalation
Daily
Dose
(
S­
T
inhalation
NOAEL
=
25
mg/
kg/
day
and
I­
T
inhalation
NOAEL
=
20
mg/
kg/
day)

*
Chemigation
is
assumed
to
have
a
similar
acreage
as
aerial
M/
L
for
typical
field
crops
(
even
if
the
crops
are
high
acreage);
this
is
also
based
on
average
crop
circle
acreage
of
approximately
100­
120
acres/
circle
with
3
circles
being
treated.
Page
51
of
52
7.2
Occupational
Postapplication
Exposure
and
Risk
The
proposed
occupational
uses
for
azoxystrobin
addressed
in
this
document
involve
foliar
applications.
Therefore,
there
is
a
potential
for
postapplication
exposure
to
scouts,
harvesters
and
other
field
workers.
However,
because
no
appropriate
dermal
endpoints
were
identified
for
this
exposure
potential,
and
postapplication
inhalation
exposure
is
expected
to
be
negligible,
an
occupational
postapplication
risk
assessment
was
not
conducted.
A
dislodgeable
foliar
residue
(
DFR)
study
for
the
use
of
azoxystrobin
on
grapes
was
submitted
to
the
Agency
previously,
but
has
not
been
employed
in
past
assessments
and
is
not
employed
in
this
assessment
because
HED
determined
there
is
no
hazard
via
the
dermal
route
(
Review
of
Acceptability
of
Data
Submitted
to
Support
the
Registration
of
New
Uses
of
Azoxystrobin,
DP
Num:
228739,
J.
Arthur,
12/
18/
96).
Non­
occupational
postapplication
risk
in
residential
settings
is
covered
in
Section
5.2
The
azoxystrobin
technical
material
has
been
classified
in
Toxicity
Category
III
for
acute
dermal
and
primary
eye
irritation,
and
Toxicity
Category
IV
for
primary
skin
irritation.
Per
the
WPS,
a
12­
hr
restricted
entry
interval
(
REI)
is
required
for
chemicals
classified
under
Toxicity
Category
III
or
IV,
which
is
the
shortest
waiting
period
permitted
under
the
WPS.
However,
per
Pesticide
Regulation
Notice
95­
3
(
6/
7/
95,
http://
www.
epa.
gov/
opppmsd1/
PR_
Notices/
pr95­
3.
html),
REIs
may
be
further
reduced
from
12
hours
if
certain
criteria
are
met
for
both
the
technical
material
and
the
different
EUPs.
In
a
previous
HED
memorandum
(
10182­
408,
10182­
415.
Response
to
Exposure
SAC
Review
of
Request
to
Add
Residential
Turf
to
Azoxystrobin
Labels
and
to
Reduce
the
Re­
Entry
Interval
to
Four
Hours,
DP
Num:
250401,
P.
Hurley,
10/
28/
98)
HED
determined
that
the
criteria
established
by
Pesticide
Regulation
Notice
95­
3
for
technical
materials
have
been
met
for
technical
azoxystrobin.
Furthermore,
RD
determined
that
the
criteria
for
the
EUPs
Abound,
Heritage
and
most
recently
Amistar
(
Azoxystrobin
80WG
EPA
File
Symbol
100­
RAU,
T.
Keigwin,
2/
27/
03,
D286344
and
Azoxystrobin
80WG
EPA
File
Symbol
100­
RAU,
T.
Keigwin,
6/
17/
03,
D288826)
have
been
met
for
these
azoxystrobin
formulations.
Therefore,
a
4­
hour
REI
is
acceptable
for
those
formulations.
The
only
other
azoxystrobin
formulation
considered
in
this
document,
A12910C,
contains
the
active
iingredient
cyproconazole
as
well.
Because
cyproconazole
does
not
meet
all
the
criteria
for
a
reduced
REI,
A12910C
does
not
meet
the
reduced
REI
criteria
either.

8.0
DATA
NEEDS
8.1
Toxicology
The
HIARC
determined
that
a
28­
day
inhalation
toxicity
study
(
nose­
only)
is
required
due
to
concern
for
occupational/
residential
exposure
via
this
route
based
on
the
current
use
pattern
(
the
90­
day
protocol
should
be
followed
with
an
exposure
duration
of
28­
days).
Page
52
of
52
8.2
Residue
Chemistry
A
new
Section
F
should
be
submitted
requesting
a
tolerance
for
the
residues
of
azoxystrobin
at
2.0
ppm
on
vegetables,
fruiting,
Group
8
(
except
tomato).

8.3
Occupational/
Residential
Label
Requirements
Heritage
®
Fungicide
­
Residential
Settings
Label
Amendment
1.
The
draft
label
specifies
a
solution
concentration,
but
no
definitive
application
rate
is
given.
The
label
should
specify
the
maximum
application
rate
(
amount
ai/
unit
area).

2.
The
draft
label
directs
the
user
to
mix
0.26
fl.
oz.
(
2
tablespoons)
of
product
with
1
gallon
of
water;
however,
1
fl.
oz.
is
equivalent
to
2
tablespoons,
therefore,
it
would
follow
that
0.26
fl.
oz.
would
be
approximately
0.5
tablespoons
(
or
1.5
teaspoons).
The
label
should
be
modified
to
eliminate
this
discrepancy.

3.
The
azoxystrobin
label
that
is
currently
registered
for
use
indoors
in
residential
settings
(
Azoxystrobin
Mold
Retardant
2.08
SC)
includes
on
the
label
use
restrictions
(
maximum
application
rate
up
to
3.3E­
5
lb
ai/
ft2,
every
3
months
as
needed,
but
not
to
exceed
4
times
per
year).
However,
unlike
the
currently
registered
label,
the
Heritage
label
amendment
specifies
no
use
restrictions;
the
label
states,
"
apply
as
needed,
when
regrowth
or
odors
are
observed
or
as
a
part
of
your
cleaning
routine."
The
Heritage
label
should
be
amended
so
it
has
use
restrictions
similar
to
the
use
restrictions
on
the
Azoxystrobin
Mold
Retardant
label.

References:
HIARC,
HED
Document
No.
013102,
12/
10/
96.
HED
RfD/
Peer
Review
Committee,
HED
Document
No.
012133,
1/
14/
97.
MARC,
DP
Num:
251683,
W.
Wassell,
12/
30/
98.
46509101CFT.
der.
wpd,
W.
Cutchin,
8/
28/
05.
PP#
5E6916,
DP
Num:
328984,
W.
Cutchin,
6/
19/
06
PP#
5E6916,
DP
Num:
328982,
W.
Cutchin,
6/
19/
06
PP#
9F06058,
DP
Num:
260134,
MRID#
s
44915206
thru
44915232
&
44983101,
M.
Nelson,
9/
06/
00.
DP
Num:
313839,
S.
Winfield,
11/
8/
05.
DP
Num:
317293,
S.
Winfield,
07/
06/
06.
PP#
s
3E6637,
3E6749,
4E6823,
&
5E6916,
DP
Num:
312949,
312951,
312953,
&
317291,
W.
Cutchin,
1/
23/
06
cc:
HED/
RAB3,
B.
Okeefe
(
HED/
RAB3),
C.
Giles­
Parker
(
RD/
FB)
