Page
13
of
30
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Isoxadifen­
Ethyl
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
­
females
13­
50
years
old
NOAEL
=
15
mg/
kg/
day
UF
=
100
aRfD
=
0.15
mg/
kg/
day
FQPA
SF
=
1x
aPAD
=
0.15
mg/
kg/
day
Rat
Developmental
Study.
Bent
scapula
in
rat
fetuses
at
the
LOAEL
of
120
mg/
kg/
day
occurred
in
the
absence
of
maternal
toxicity.

Acute
Dietary
­
general
population
including
infants
and
children
­­
­­
None.
No
appropriate
toxicological
endpoint
attributable
to
a
single
exposure
was
identified
for
this
population
subgroup
in
the
available
toxicology
studies.

Chronic
Dietary
­
all
populations
NOAEL
=
3.3
mg/
kg/
day
UF
=
100
cRfD
=
0.033
mg/
kg/
day
FQPA
SF
=
1x
cPAD
=
0.033
mg/
kg/
day
1­
year
dog
feeding
study,
(
co­
critical)
90­
day
dog
feeding
study.
Kidney
histopathology
in
both
sexes
of
dogs
in
both
studies
at
the
LOAEL
of
6.1
mg/
kg/
day
Short­
Term
Dermal,
Inhalation,
and
Incidental
Oral
(
1­
7
days)
Oral
NOAEL=
13.8
mg/
kg/
day
dermal
absorption
rate
=
14%
inhalation
absorption
rate=
100%
LOC
for
MOE
<
100
(
occupational
and
residential)
90­
day
rat
feeding
study.
Decreased
body
weight
and
weight
gain
at
day
8
in
90­
day
rat
feeding
study
at
LOAEL
of
137.9
mg/
kg/
day
Intermediate­
(
1­
6
months)
and
Long­
Term
(>
6
months)
Dermal
and
Inhalation
and
Intermediate­
term
(
1­
6
months
Incidental
Oral)
Oral
NOAEL=
3.3
mg/
kg/
day
dermal
absorption
rate
=
14%
inhalation
absorption
rate=
100%
LOC
for
MOE
<
100
(
occupational
and
residential)
1­
year
dog
feeding
study,
(
co­
critical)
90­
day
dog
feeding
study.
Kidney
histopathology
in
both
sexes
of
dogs
in
both
studies
at
the
LOAEL
of
6.1
mg/
kg/
day
Cancer
(
oral,
dermal,
inhalation)
Cancer
classification
­
"
not
likely
to
be
a
human
carcinogen"
Risk
Assessment
not
required
No
evidence
of
carcinogenicity
3.4
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(
FIFRA)
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
has
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
isoxadifen­
ethyl
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
Page
14
of
30
4.0
EXPOSURE
ASSESSMENT
4.1
Summary
of
Registered
Uses
Table
4.
Summary
of
Registered
Use
Patterns
for
Isoxadifen­
ethyl
Crops
rice
field
corn
Formulated
product
emulsifiable
concentrate
water
soluble
granule
Use
annual
grassy
weeds
broadleaf
weeds,
annual
and
perennial
grasses
Application
methods
(
min
spray
vol)
aerial
and
groundboom
sprayer
(
10
gal/
acre)
aerial
and
groundboom
sprayer
(
5
gal/
acre)

Maximum
application
rate
0.083
lb.
safener/
acre
0.023­
0.036
lb.
safener/
acre
Maximum
number
of
applications
twice
per
season
twice
per
season
Maximum
seasonal
application
rate
0.15
lb.
safener/
acre
0.073
lb.
safener/
acre
Timing
and
frequency
of
applications
apply
from
1­
leaf
to
early
tillering
(
before
panicle
initiation);
retreatment
interval
(
RTI)
14
days;
preharvest
Interval
(
PHI)
=
65
days
apply
from
emergence
to
V6
growth
stage
(
0­
20
inches
height);
only
by
ground
drop
nozzle
application
from
V6
to
V8
growth
stage
(
20­
36
inches);
PHI
for
corn
grain
=
70
days;
PHI
for
corn
forage
=
45
days
Restrictions
S
water
must
be
drained
from
the
rice
fields
before
application.;
allow
at
least
24
hours
following
application
before
initiation
of
the
paddy
flood
S
do
not
use
in
areas
where
catfish
and
crayfish
are
commercially
cultured;

S
treated
paddy
water
should
not
be
used
to
irrigate
crops
not
registered
for
use
within
14
days
of
the
last
application
of
this
product
S
a
treated
field
may
not
be
rotated
to
any
corp
within
9
months,
after
9
months
only
soybeans
may
be
planted
S
do
not
use
on
sweet
corn,
popcorn,
or
corn
grown
for
seed
4.2
Summary
of
Proposed
Uses
The
proposed
application
directions
for
turf
are
adequate.
Table
5
is
a
summary
of
the
proposed
turf
application
scenario.

Table
5.
Summary
of
Proposed
Turf
Use
Pattern
for
Isoxadifen­
ethyl
Crops
turf
Formulated
product
soluble
concentrate
(
SC)

Use
herbicide
safener
Application
methods
foliar
spray
(
spray
volume
of
30­
60
gallons/
acre)

Maximum
application
rate
0.0069
to
0.04
lb
safener/
acre
Maximum
number
of
applications
twice
per
season
Maximum
seasonal
application
rate
0.085
lb.
safener/
acre
Timing
and
frequency
of
applications
application
in
the
spring
during
transition
from
dormancy
to
activity
Page
15
of
30
Restrictions
restricted
reentry
interval
­
12
hours
­

4.3
Dietary
Exposure/
Risk
Pathway
4.3.1
Residue
Profile
HED
has
previously
reviewed
the
residue
chemistry
data
associated
with
the
application
of
isoxadifen­
ethyl
to
rice
and
field
corn
(
D264135,
W.
Donovan,
16­
Feb­
2001;
D266326,
W.
Donovan,
20­
Feb­
2001).
Several
residue
chemistry
deficiencies
were
noted.
HED
performed
a
risk
assessment
and
concluded
that
time­
limited
tolerances
were
appropriate
(
D272957,
W.
Donovan
et
al.,
24­
Mar­
2001).
The
petitioner
has
subsequently
sent
information,
which
HED
has
reviewed,
addressing
the
residue
chemistry
deficiencies
(
D273751,
W.
Donovan,
11­
Apr­
2001;
D277090,
W.
Donovan,
6­
Sep­
2001;
and
D278331,
W.
Donovan,
25­
Oct­
2001;
D295710,
T.
Bloem,
16­
Oct­
2003).
Based
on
these
additional
data,
the
petitioner
requested
conversion
of
the
currently
established
time­
limited
tolerances
to
permanent
tolerances.

Nature
of
the
Residue
­
Plants:
Metabolism
data
were
submitted
for
rice
and
corn.
The
MARC
determined
that
for
rice
the
residues
of
concern,
for
tolerance
expression
and
risk
assessment
purposes,
are
parent,
AE
F129431,
and
AE
C637375,
and
that
for
corn
the
residues
of
concern,
for
the
tolerance
expression
and
risk
assessment
purposes,
are
parent
and
AE
F129431
(
D271419,
W.
Donovan
and
W.
Dykstra,
10­
Jan­
2001).
The
selection
of
the
residues
of
concern
was
based
on
levels
of
the
metabolites
found
in
the
metabolism
and
magnitude
of
the
residue
studies.

Nature
of
the
Residue
­
Livestock:
Metabolism
data
were
submitted
for
livestock
commodities
derived
from
hens
and
dairy
cows.
The
HED
MARC
determined
that
for
livestock
commodities
the
residues
of
concern,
for
tolerance
expression
and
risk
assessment
purposes,
are
parent
and
AE
F129431
(
D271419,
W.
Donovan
and
W.
Dykstra,
10­
Jan­
2001).
This
decision
was
based
on
the
finding
that
metabolite
AE
F129431
is
the
only
compound
found
in
significant
quantities
in
livestock
commodities.

Residue
Analytical
Methods:
The
analytical
methods
used
in
the
field
trial
and
processing
studies
have
been
adequately
validated
and
are
appropriate
for
data
collection
purposes.
The
petitioner
proposed
a
capillary
gas
chromatography/
mass
selective
detection
(
GC/
MSD)
method
for
enfocement
of
the
rice
and
field
corn
tolerances.
The
Analytical
Chemistry
Branch
(
ACB)
determined
that
the
method
is
suitable
for
enforcement
of
the
rice
and
field
corn
tolerances
(
D293176,
T.
Bloem,
28­
Aug­
2003).
HED
forwarded
the
method
to
the
U.
S.
Food
and
Drug
Administration
for
publication
in
the
Pesticide
Analytical
Manual
II
(
D293179,
T.
Bloem,
28­
Aug­
2003).

Multiresidue
Method
(
MRM):
Isoxadifen­
ethyl
was
adequately
recovered
in/
on
rice
grain
using
Protocol
E
(
Method
303)
and
in/
on
corn
meal
using
Protocol
F
(
Method
304).
Residues
of
AE
F129431
were
recovered
quantitatively
in/
on
rice
grain
using
Protocol
B.
No
data
were
provided
on
the
recovery
of
metabolite
AE
C637375
from
the
FDA
multiresidue
protocols.
MRM
testing
data
for
AE
C637375
are
required.
Upon
submission
of
these
data,
HED
will
forward
to
FDA
the
MRM
testing
results
for
isoxadifen­
ethyl,
AE
F129431,
and
AE
C637375.
Page
16
of
30
Rice
Magnitude
of
the
Residue
Data:
An
adequate
number
of
geographically­
representative
rice
field
trials
were
provided
to
indicate
that
tolerances
for
the
combined
residues
of
isoxadifen­
ethyl,
AE
F129431,
and
AE
C637375
of
0.10
and
0.25
ppm
in/
on
rice
grain
and
straw,
respectively,
are
appropriate.
For
rice
grain,
all
residues
were
less
than
the
limit
of
quantitation
(
LOQ)
of
0.02
ppm
except
for
one
sample
where
AE
C637375
was
detected
at
0.04
ppm.
For
rice
straw,
the
maximum
residue
of
AE
F129431
was
0.15
ppm,
while
all
samples
had
residues
of
isoxadifen­
ethyl
and
AE
C637375

0.05
ppm
(
LOQ).

Corn
Magnitude
of
the
Residue
Data:
An
adequate
number
of
geographically­
representative
corn
field
trials
were
provided
to
indicate
that
tolerances
for
the
combined
residues
of
isoxadifen­
ethyl
and
AE
F129431
of
0.10,
0.10,
and
0.20
ppm
in/
on
corn
grain,
forage,
and
stover,
respectively,
are
appropriate.
For
corn
grain
samples
treated
at
1x
the
maximum
seasonal
rate,
the
maximum
residue
of
AE
F129431
was
0.06
ppm,
while
isoxadifen­
ethyl
residues
were
<
0.02
ppm
(
LOQ).
For
all
corn
forage
samples
treated
at
1x
the
maximum
seasonal
rate,
isoxadifen­
ethyl
and
AE
F129431
residues
were
less
than
the
LOQ
of
0.05
ppm.
For
corn
stover
samples
treated
at
1x
the
maximum
seasonal
rate,
the
maximum
residue
of
AE
F129431
was
0.13
ppm,
while
isoxadifen­
ethyl
residues
were
<
0.05
ppm
(
LOQ).

Processed
Food/
Feed
­
Rice:
The
petitioner
submitted
an
adequate
rice
processing
study
conducted
at
5.1x
the
maximum
seasonal
application
rate.
The
resulting
data
indicate
that
the
combined
residues
of
isoxadifen­
ethyl,
AE
F129431,
and
AE
C637375
are
reduced
in
polished
rice
(
0.54x)
and
in
rice
bran
(
0.87x)
and
concentrate
in
rice
hull
(
4.04x).
Based
on
these
data,
HED
concludes
that
a
tolerance
in/
on
rice
bran
is
not
necessary
and
the
currently
established
rice
bran
tolerance
should
be
eliminated.
Additionally,
based
on
the
highest
average
field
trial
residue
(<
0.08
ppm)
and
the
4.04x
processing
factor
for
rice
hull,
HED
concludes
that
the
currently
established
0.50
ppm
rice
hull
tolerance
is
appropriate
(
0.08
x
4.04
=
0.32).

Processed
Food/
Feed
­
Corn:
The
petitioner
submitted
an
adequate
field
corn
processing
study
conducted
at
4.5x
the
maximum
seasonal
application
rate.
The
resulting
data
indicate
that
the
combined
residues
of
isoxadifen­
ethyl
and
AE
F122006
were
below
the
method
LOQ
(<
0.02
ppm
each)
in/
on
the
unprocessed
field
corn
grain.
Since
residues
were
<
LOQ
in/
on
the
raw
agricultural
commodity
when
treated
at
~
5x
the
maximum
proposed
application
rate,
HED
concluded
that
tolerances
in/
on
field
corn
processed
commodities
are
unnecessary.

Meat,
Milk,
Poultry,
Eggs:
Based
on
the
maximum
theoretical
dietary
burdens
and
available
metabolism
studies
on
hen
and
dairy
cattle,
HED
concludes
that
tolerances
are
unnecessary
for
ruminant
and
poultry
commodities
at
this
time
(
40
CFR
180.6(
a)(
3).

Confined
Accumulation
in
Rotational
Crops:
The
petitioner
submitted
a
confined
rotational
crop
study
conducted
with
[
14C­
phenyl]
isoxadifen­
ethyl
at
0.080
lb
ai/
acre
(
1x
and
0.5x
the
maximum
seasonal
rate
for
corn
and
rice,
respectively).
The
treated
plots
were
planted
30
days
after
application
with
radishes,
wheat,
lettuce,
and
soybean.
Total
radioactive
residues
(
TRRs)
were
all
less
than
0.01
ppm
(
0.003­
0.009
ppm),
with
the
exception
of
wheat
straw
at
0.012
ppm.
Based
on
these
data,
HED
concludes
that
crop
rotation
restrictions
for
isoxadifen­
ethyl
use
with
field
corn
are
unnecessary.
Since
the
application
rate
for
the
confined
study
was
0.5x
the
maximum
rate
for
rice,
the
results
from
this
study
are
not
applicable
to
rice.
The
petitioner
indicated
that
in
order
to
make
the
rice
product
viable,
rotation
to
only
soybeans
with
a
9­
month
plant­
back
interval
is
necessary.
Page
17
of
30
Based
on
the
available
data,
HED
concludes
that
this
rotation
crop
interval
is
appropriate
and
no
tolerances
in/
on
rotational
crops
are
necessary.
If
the
petitioner
would
like
to
allow
rotation
to
crops
other
than
soybeans
following
application
to
a
rice
field
or
established
a
shorter
plant­
back
interval
for
soybeans,
then
the
petitioner
should
conduct,
at
a
minimum,
an
adequate
rotational
crop
study
which
depicts
the
nature
and
magnitude
of
the
residues
in
rotational
crops
relative
to
the
rice
application
rate.

4.3.2
Dietary
Exposure
Analysis
Isoxadifen­
ethyl
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
DEEMFCID
 
(
Ver
1.30),
which
incorporates
consumption
data
from
USDA's
CSFII,
1994­
1996
and
1998.
The
1994­
96,
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
EPAdefined
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.
Based
on
analysis
of
the
1994­
96,
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
years,
children
3­
5
years,
children
6­
12
years,
youth
13­
19
years,
adults
20­
49
years,
females
13­
49
years,
and
adults
50+
years
old.

For
chronic
dietary
exposure
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food­
form
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(
i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
(
i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.

The
acute
and
chronic
analyses
assumed
tolerance
level
residues,
100%
crop
treated,
and
DEEM
(
ver.
7.76)
default
concentration
factors
for
all
commodities
(
D295708,
T.
Bloem,
29­
Oct­
2003).
The
acute
dietary
food
exposure
estimates
to
isoxadifen­
ethyl
were
<
1.0%
aPAD
for
females
13
 
49
years
old
and
are
therefore
less
than
HED's
level
of
concern
(
endpoint
not
identified
for
the
remaining
populations
subgroups).
The
chronic
dietary
exposure
estimates
were

1.5%
cPAD
for
all
population
subgroups
and
are
therefore
less
than
HED's
level
of
concern
(
highest
exposed
population
subgroup
­
children
3­
5
years
old).
Table
6
is
a
summary
of
the
acute
and
chronic
dietary
exposure
estimates.
Page
18
of
30
Table
6.
Summary
of
Dietary
Exposure
and
Risk
for
Isoxadifen­
Ethyl
Population
Subgroup
Acute
Dietary
(
95th
Percentile)
Chronic
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
no
endpoint
identified
0.000216
<
1.0
All
Infants
(<
1
year
old)
0.000339
1
Children
1­
2
years
old
0.000427
1.3
Children
3­
5
years
old
0.000486
1.5
Children
6­
12
years
old
0.000373
1.1
Youth
13­
19
years
old
0.000294
<
1.0
Adults
20­
49
years
old
0.000182
<
1.0
Adults
50+
years
old
0.000099
<
1.0
Females
13­
49
years
old
0.000511
<
1.0
0.000177
<
1.0
4.4
Water
Exposure/
Risk
Pathway
The
following
information
concerning
the
environmental
fate
and
drinking
water
assessment
of
isoxadifen­
ethyl
was
provided
by
EFED
(
D272138,
H.
Craven
and
A.
Clem,
02­
Feb­
2001).

Environmental
Fate
Assessment:
Isoxadifen­
ethyl
breaks
down
rapidly
in
the
environment
to
form
the
corresponding
carboxylic
acid
(
AE
F129431).
Acid
AE
F129431
is
relatively
short­
lived
in
soil
and
water,
with
variable
half­
lives
of
approximately
1­
2
weeks.
The
acid
is
also
highly
mobile,
as
indicated
by
Freundlich
soil
organic
carbon
coefficients
(
Kfoc)
in
four
soils
of
approximately
70,
80,
70,
and
180
Freundlich
units,
where
masses
are
in
grams
and
volumes
in
milliliters
(
median
Kfoc
=
78,
average
Kfoc
=
100;
median
1/
n
=
0.83,
average
1/
n
=
0.83).

In
aerobic
and
anaerobic
aquatic
environments,
the
acid
degrades
to
give
the
nitrile
AE
C637375
and
the
amide
AE
C642961.
In
reported
studies,
the
nitrile
reached
its
highest
concentration
in
an
anaerobic
soil
system
of
approximately
88%
of
the
radiolabeled
dose,
while
in
an
anaerobic
aquatic
system
it
reached
approximately
75%
of
the
dose.
In
aquatic
aerobic
systems,
maximum
nitrile
concentrations
reached
35­
45%
of
the
dose.
The
nitrile
appears
to
have
a
longer
half­
life
in
aquatic
environments
than
the
parent
or
acid,
but
no
values
were
given.
The
amide
had
a
maximum
concentration
of
20­
22%
of
the
radiolabeled
dose
in
the
aerobic
aquatic
studies.
In
the
anaerobic
aquatic
system,
the
maximum
concentration
of
the
amide
was
approximately
10­
11%
of
the
dose.
In
the
anaerobic
soil
study,
the
amide
reached
only
approximately
4%
of
the
dose.
None
of
the
degradates
are
expected
to
bioconcentrate
to
any
significant
extent.
Volatilization
of
parent
and
the
metabolites
is
not
expected
to
be
a
significant
route
of
dissipation.

Ground
and
Surface
Water
EECs:
The
HED
MARC
determined
that
the
residues
of
concern
in
drinking
water
are
isoxadifen­
ethyl,
AE
F129431,
AE
C637375,
and
AE
C642961
(
D271419,
W.
Donovan
and
W.
Dykstra,
10­
Jan­
2001).
Since
ground
or
surface
water
monitoring
data
are
not
avialable,
concentrations
of
the
residues
of
concern
in
surface
and
ground
water
were
made
using
computer
modeling.
The
tier
1
acute
and
chronic
EECs
for
surface
water
from
GENEEC
are
80
and
40
ppb,
respectively.
The
acute
and
chronic
EEC
for
ground
water
from
SCI­
GROW
is
5
ppb.
Both
models
assumed
a
maximum
seasonal
application
rate
of
0.147
lb
ai/
acre
(
rice
application
rate,
highest
registered/
proposed
application
rate).
Page
19
of
30
4.5
Residential/
Non­
Occupational
Exposure
Pathway
Spray
Drift:
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
groundboom
application
methods.
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
data
base
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
offtarget
drift
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.

Exposure
from
Proposed
Turf
Use:
The
proposed
turf
use
is
intended
for
professional
application
to
Bermudagrass
on
golf
courses,
sod
farms,
residential
and
commercial
site
lawns,
parks,
recreational
facilities,
and
similar
sites.
It
is
not
intended
for
use
by
homeowners
or
other
nonprofessional
applications.
Therefore,
residential
mixer/
loader
and
applicator
exposures
are
not
anticipated.
The
following
short­
term
post­
application
residential
exposures
are
anticipated:
adult
(
dermal
­
golf
course
and
residential
lawn),
child
(
dermal
­
residential
lawn),
and
toddler
(
dermal
and
incidental
oral
­
residential
lawn).
Since
a
common
endpoint
has
been
identified
for
short­
term
dermal
and
incidental
oral
endpoints,
these
exposures
were
aggregated.
The
residential
exposure
assessment
was
conducted
using
the
procedures
in
the
HED
Residential
SOPs
and
as
modified
by
SOP
No.
12
(
D295128,
M.
Dow,
22­
Oct­
2003).

Dermal
Exposure:
Short­
term
dermal
exposures
for
golfers
were
not
calculated
as
the
assumptions
made
when
performing
this
assessment
result
in
dermal
exposures
less
than
those
resulting
from
a
residential
lawn
application.
Therefore,
the
following
discussion
refers
only
to
short­
term
dermal
exposure
resulting
form
lawn
application
in
the
residential
setting.

The
default
turf
transferable
residue
(
TTR)
estimate
on
the
day
of
application
is
5%
of
the
application
rate
based
on
the
HED
Residential
SOPs.
Based
on
the
maximum
application
rate
of
0.04
lb
ai/
acre
(
0.00045
mg/
cm2),
the
default
day
0
dislodgeable
foliar
residue
(
DFR)
value
is
0.0000225
mg/
cm2.
SOP
12
has
also
established
turf
transfer
coefficients
of
14,500
cm2/
hr
for
adults
and
5,200
cm2/
hr
for
children.
A
two­
hour
exposure
duration
has
been
established
by
the
Residential
SOPs
and
is
used
in
this
assessment.
The
body
weights
for
adults
and
children
are
70
kg
and
15
kg,
respectively.
Based
on
these
values,
the
daily
dermal
adult
and
child
post
application
lawn
exposure
estimates
are
calculated
as
follows:

adult:
0.0000225
mg/
cm2
x
14,500
cm2/
hr
x
2
hr/
day
÷
70
kg
=
0.0093
mg/
kg
bw/
day
child:
0.0000225
mg/
cm2
x
5,200
cm2/
hr
x
2
hr/
day
÷
15
kg
=
0.016
mg/
kg
bw/
day
Page
20
of
30
Incidental
Oral
Exposure:
Hand
to
mouth
(
HTM),
object
to
mouth
(
OTM),
and
soil
hand
to
mouth
short­
term
incidental
oral
exposures
may
occur
as
a
result
of
the
proposed
turf
use.
Soil
hand
to
mouth
exposure
was
not
assessed
by
the
petitioner.
HED
believes
that
under
current
policy
the
soil
hand
to
mouth
exposure
will
be
negligible
and
will
not
impact
the
current
risk
assessment.
Therefore
the
following
discussion
pertains
only
to
HTM
and
OTM
short­
term
incidental
oral
exposures.

SOP
12
provides
defaults
for
hand
to
mouth
(
HTM)
and
object
to
mouth
(
OTM)
exposure.
HTM
exposure
assumes
the
5%
transfer
from
turf
to
hands
with
a
20
cm2
hand
surface
area
contact
in
the
mouth,
20
insertions
per
hour
during
the
two
hour
exposure
duration,
and
100%
transference
of
residue
from
the
hands
to
mouth.
The
OTM
defaults
assume
20%
transference
of
residue
from
the
turf
to
the
object,
a
total
contact
of
25
cm2/
day,
and
100%
transfer
of
residue
from
the
object
to
the
mouth.
The
20%
residue
of
the
initial
0.00045
mg/
cm2
application
rate
is
0.00009
mg/
cm2.
Based
on
these
defaults
and
the
15
kg
body
weight
the
HTM
and
OTM
exposures
are
as
follows:

HTM:
0.0000225
mg/
cm2
x
20
cm2/
insert
x
20
inserts/
hr
x
2
hr/
day
÷
15
kg
=
0.0012
mg/
kg/
day
OTM:
0.00009
mg/
cm2
x
25
cm2/
day
÷
15
kg
=
0.00015
mg/
kg/
day
Incidental
Oral
and/
or
Dermal
MOEs:
The
total
estimated
adult
exposure
is
0.0093
mg/
kg/
day
and
the
total
estimated
child
exposure
is
the
sum
of
the
dermal,
HTM,
and
OTM
exposures
or
0.0174
mg/
kg/
day.
Based
on
the
NOEL
of
13.8
mg/
kg/
day
the
MOEs
for
an
adult
and
child
following
a
professional
lawn
or
turf
application
are
as
follows:

adult:
13.8
mg/
kg/
day
÷
0.0093
mg/
kg/
day
=
1500
child:
13.8
mg/
kg/
day
÷
0.0174
mg/
kg/
day
=
790
HEDs
LOC
is
for
MOEs
<
100.
Therefore,
the
proposed
turf
use
does
not
exceed
HEDs
level
of
concern.
Page
21
of
30
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
HED
conducts
aggregate
exposure
assessments
by
summing
dietary
(
food
and
water)
and
residential
exposures
(
residential
or
other
non­
occupational
exposures).
Based
on
the
proposed/
registered
uses
for
isoxadifen­
ethyl,
acute,
short­
term,
and
chronic
aggregate
exposure
assessments
were
calculated.
Since
HED
does
not
have
ground
or
surface
water
monitoring
data
to
calculate
quantitative
aggregate
exposure,
DWLOCs
were
calculated.
The
DWLOC
is
the
theoretical
upper
limit
of
a
chemical's
concentration
in
drinking
water
that
will
result
in
aggregate
exposures
less
than
HED's
level
of
concern.
DWLOC
values
are
not
regulatory
standards
for
drinking
water.
DWLOCs
were
calculated
using
the
following
standard
body
weights
and
drinking
water
consumption
figures:
70kg/
2L
(
adult
male
and
US
Population),
60
kg/
2L
(
adult
female
and
youth),
and
10kg/
1L
(
infant
&
children).

5.1
Acute
Aggregate
Risk
The
acute
dietary
exposure
analysis
assumed
tolerance
level
residues,
100%
crop
treated,
and
DEEM
(
ver
7.76)
default
processing
factors
for
all
commodities.
The
EECs
generated
by
EFED
are
less
than
HED's
DWLOCs.
Thus,
acute
aggregate
risk
estimates
are
below
HED's
level
of
concern.
Table
7
summarizes
the
acute
aggregate
exposure
to
isoxadifen­
ethyl.

Table
7.
Acute
Aggregate
Exposure
Population
Subgroup
aPAD
mg/
kg/
day
Food
Exp
mg/
kg/
day
Max
Water
Exp1
mg/
kg/
day
Surface
Water
EEC2
(
ppb)
Ground
Water
EEC2
(
ppb)
DWLOC3
(
ppb)

Females
(
13­
50
years
old)
0.15
0.000511
0.149489
80
5
4500
1
maximum
water
exposure
(
mg/
kg/
day)
=
cPAD
(
mg/
kg/
day)
­
food
exposure
(
mg/
kg/
day)
2
EECs
generated
using
the
GENEEC
and
SCI­
GROW
models
assuming
a
maximum
seasonal
application
rate
of
0.147
lb
ai/
acre
(
registered
rice
application
scenario)
3
DWLOC
=
(
maximum
water
exposure)
x
(
body
weigth)
x
(
1000
µ
g/
mg)
÷
(
liter/
day)
Page
22
of
30
5.2
Short­
Term
Aggregate
Risk
Since
the
proposed
turf
use
is
expected
to
result
in
non­
occupational
exposures
for
adults
(
dermal),
children
(
dermal),
and
infants
(
incidental
oral
and
dermal)
and
since
a
common
endpoint
has
been
identified
for
assessment
of
short­
term
oral
and
dermal
exposures
(
decreased
body
weight
and
decreased
weight
gain),
a
short­
term
aggregate
exposure
assessment
considering
exposure
from
food,
water,
and
non­
occupational
sources
is
necessary.
Short­
term
exposure
has
been
defined
as
from
1­
30
days
and
HED
has
concluded
that
chronic
dietary
exposure
estimates
will
more
accurately
reflect
actual
exposure
over
these
time
periods
than
will
high
end
(
acute)
exposures.
The
residential
lawn
application
of
isoxadifen­
ethyl
is
expected
to
result
in
the
highest
short­
term
dermal
and
incidental
oral
exposures.
Therefore,
the
short­
term
aggregate
exposure
assessment
used
the
chronic
dietary
and
residential
lawn
(
incidental
oral
and/
or
dermal)
exposure
estimates.
Since
the
acceptable
MOE
for
each
route
of
exposure
is
identical
(
MOEs
>
100),
the
short­
term
aggregate
exposure
assessment
was
calculated
using
the
reciprocal
MOE
approach.

The
chronic
dietary
exposure
analysis
assumed
tolerance
level
residues,
100%
crop
treated,
and
DEEM
(
ver
7.76)
default
processing
factors
for
all
commodities.
The
residential
dermal
and
incidental
oral
exposure
estimates
were
calculated
using
the
procedures
in
the
HED
Residential
SOPs
as
modified
by
SOP
No.
12
and
are
considered
screening
level.
The
Tier
1
chronic
EECs
generated
by
EFED
are
less
than
HED's
DWLOC
(
for
all
population
subgroups).
Thus,
short­
term
aggregate
risk
estimates
are
below
HED's
level
of
concern.
Table
8
summarizes
the
short­
term
aggregate
exposure
to
isoxadifen­
ethyl.
Page
23
of
30
Table
8.
Short­
Term
Aggregate
Exposure
Population
Target
Agg
MOE1
MOE
food2
MOE
dermal3
MOE
incidental
oral4
Agg
MOE
(
food
&
res)
5
MOE
water6
Allowable
water
exposure7
(
mg/
kg/
day)
Ground
Water
EEC8
(
ppb)
Surface
Water
EEC8
(
ppb)
DWLOC9
(
ppb)

General
U.
S.
Population
100
63889
1484
­­
1450
107
0.128484
5
40
4500
All
Infants
(<
1
year
old)
40708
863
10222
780
115
0.120311
1200
Children
1­
2
years
old
32319
863
10222
776
115
0.120223
1200
Children
3­
5
years
old
28395
863
10222
774
115
0.120164
1200
Children
6­
12
years
old
36997
863
10222
779
115
0.120277
1200
Youth
13­
19
years
old
46939
1484
­­
1438
107
0.128406
3900
Adults
20­
49
years
old
75824
1484
­­
1455
107
0.128518
4500
Adults
50+
years
old
139394
1484
­­
1468
107
0.128601
4500
Females
13­
49
years
old
77966
1484
­­
1456
107
0.128523
3900
1
total
UFs
for
all
routes
of
exposure
is
100x;
therefore,
the
target
MOE
is
100
2
MOE
food
=
short­
term
incidental
oral
NOAEL
÷
chronic
dietary
exposure
3
MOE
dermal
=
short­
term
dermal
NOAEL
÷
dermal
residential
exposure
(
see
Section
4.5)

4
MOE
incidental
oral
=
short­
term
incidental
oral
NOAEL
÷
incidental
oral
exposure
(
see
Section
4.5)

5
aggregate
MOE
(
food
and
residential)
=
1
÷
(
(
1
÷
MOEfood)
+
(
1
÷
MOEdermal)
+
(
1
÷
MOEincidental
oral))

6
water
MOE
=
1
÷
((
1
÷
Target
Aggregate
MOE)
­
(
1
÷
Aggregate
MOE
(
food
and
residential)))

7
allowable
water
exposure
=
short­
term
oral
NOAEL
÷
MOE
water
8
EECs
generated
using
the
GENEEC
and
SCI­
GROW
models
assuming
a
maximum
seasonal
application
rate
of
0.147
lb
ai/
acre
(
registered
rice
application
scenario)

9
DWLOC(

g/
L)
=
(
allowable
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)
x
1000

g/
mg)
÷
(
water
consumption
(
liters))
Page
24
of
30
5.3
Chronic
Aggregate
Risk
The
chronic
dietary
exposure
analysis
assumed
tolerance
level
residues,
100%
crop
treated,
and
DEEM
(
7.76)
default
processing
factors
for
all
commodities.
The
EECs
generated
by
EFED
are
less
than
HED's
DWLOCs.
Thus,
chronic
aggregate
risk
estimates
are
below
HED's
level
of
concern.
Table
9
summarizes
the
chronic
aggregate
exposure
to
isoxadifen­
ethyl.

Table
9.
Chronic
Aggregate
Exposures
to
Isoxadifen­
ethyl
Residues
Population
cPAD
(
mg/
kg/
day)
Chronic
Food
Exposure
(
mg/
kg/
day)
Max
Chronic
Water
Exposure1
(
mg/
kg/
day)
Ground
Water
EEC2
(
ppb)
Surface
Water
EEC2
(
ppb)
Chronic
DWLOC3
(
ppb)

General
U.
S.
Population
0.033
0.000216
0.032784
5
40
1100
All
Infants
(<
1
year
old)
0.000339
0.032661
330
Children
1­
2
years
old
0.000427
0.032573
330
Children
3­
5
years
old
0.000486
0.032514
320
Children
6­
12
years
old
0.000373
0.032627
330
Youth
13­
19
years
old
0.000294
0.032706
980
Adults
20­
49
years
old
0.000182
0.032818
1100
Adults
50+
years
old
0.000099
0.032901
1200
Females
13­
49
years
old
0.000177
0.032823
980
1
maximum
water
exposure
(
mg/
kg/
day)
=
cPAD
(
mg/
kg/
day)
­
food
exposure
(
mg/
kg/
day)
2
EECs
generated
using
the
GENEEC
and
SCI­
GROW
models
assuming
a
maximum
seasonal
application
rate
of
0.147
lb
ai/
acre
(
registered
rice
application
scenario)
3
DWLOC
=
(
maximum
water
exposure)
x
(
body
weigth)
x
(
1000
µ
g/
mg)
÷
(
liter/
day)
Page
25
of
30
6.0
CUMULATIVE
RISK
Section
408(
b)(
2)(
D)(
v)
of
the
FFDCA
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
isoxadifen­
ethyl
has
a
common
mechanism
of
toxicity
with
other
substances.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
isoxadifen­
ethyl
and
any
other
substances
and
isoxadifen­
ethyl
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
isoxadifen­
ethyl
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

7.0
OCCUPATIONAL
EXPOSURE
HED
has
previously
evaluated
the
occupational
exposures
to
isoxadifen­
ethyl
resulting
from
the
registered
application
scenarios
for
rice
and
corn
(
D273606,
T.
Swackhammer,
26­
Mar­
2001).
The
following
is
a
summary
of
this
review.
Based
on
the
rice
and
corn
use
patterns,
commercial
handlers
are
expected
to
have
short­
and
intermediate­
term
dermal
and
inhalation
exposures.
Growers
are
expected
to
have
short­
term
dermal
and
inhalation
exposures.
Workers
entering
fields
following
applications
are
anticipated
to
have
short­
term
dermal
exposures.
Since
the
dermal
and
inhalation
endpoints
are
from
the
same
toxicological
study,
these
exposures
were
combined.
The
combined
(
dermal
and
inhalation)
short­
term
and
intermediate­
term
MOEs,
with
the
label
required
personal
protective
equipment,
ranged
from
2,100­
21,000
and
510­
5,000,
respectively
(
inhalation
MOEs
ranged
from
7,800­
92,000).
Since
the
calculated
MOEs
are
>
100,
they
do
not
exceed
HED's
level
of
concern.

Based
on
the
proposed
turf
use
pattern
(
see
Table
4),
HED
anticipates
short­
term
dermal
and
inhalation
exposures
to
commercial
mixer/
loaders
supporting
groundboom
operations;
to
groundboom
applicators;
and
to
lawn
care
operators
who
mix,
load,
and
apply
the
material.
Workers
entering
fields
following
applications
are
anticipated
to
have
short­
term
dermal
exposures.
Since
a
common
endpoint
has
been
identified
for
short­
term
dermal
and
inhalation
exposures,
these
exposures
were
aggregated.
The
occupational
exposure
assessment
is
based
on
surrogate
data
from
the
following
sources:
(
1)
PHED,
Version
1.1
(
August,
1998);
(
2)
ORETF,
study
OMA002
"
Exposure
of
Professional
Lawn
Care
Workers
During
the
Mixing
and
Loading
of
Dry
and
Liquid
Formulations
and
the
Liquid
Application
of
Turf
Pesticides
Utilizing
a
Surrogate
Compound"
(
Bayer
CropScience
is
a
member
of
ORETF);
and
(
3)
the
ARTF
study
ARF035
regarding
turf
farm
re­
entry
exposures.
For
a
full
review
of
the
occupational
exposure
assessment
see
D295128
(
M.
Dow,
22­
Page
26
of
30
Oct­
2003).
1
Integrated
Report
for
Evaluation
of
Potential
Exposures
to
Homeowners
and
Professional
Lawn
Care
Operators
Mixing,
Loading,
and
Applying
Granular
and
Liquid
Pesticides
to
Residential
Lawns.
12
March
1999.
MRID
No.
44972201.

Page
27
of
30
7.1
Handler
Exposure
Assumptions
and
Risk
Assessments
Groundboom
Applications:
The
Pesticide
Handlers
Exposure
Database
(
PHED),
jointly
developed
by
Health
Canada,
the
U.
S.
Environmental
Protection
Agency
(
EPA),
and
Crop
Life
America
(
CLA),
was
used
to
estimate
the
dermal
and
inhalation
exposures
resulting
from
the
application
of
isoxadifen­
ethyl
to
sod
farms
and
golf
courses.
The
general
procedure
used
to
develop
quantitative
measures
of
exposure
from
this
database
is
to
create
subsets
of
overall
data
based
on
the
specific
use
pattern.
Several
such
subsets
are
typically
created;
the
most
appropriate
one
is
selected
based
on
amount
and
quality
of
data
and
similarity
to
the
use
pattern
of
interest.

For
initial
assessments
the
PHED
Surrogate
Exposure
Guide
developed
by
the
Agency
(
August
1998)
is
used
to
estimate
the
dermal
and
inhalation
exposure
potentials.
Because
the
formulation
is
a
soluble
concentrate,
Scenario
3:
All
liquids,
open
mixing
and
loading
is
applicable
to
handle
the
mixing
loading
portion
for
the
groundboom
uses.
Scenario
13:
Groundboom
application,
open
cab
is
used
to
address
the
application
exposure.

The
Scenario
3
dermal
exposure
potential
for
a
mixer/
loader
wearing
the
label
required
long­
sleeved
shirt,
long
pants,
and
protective
gloves
is
0.023
mg/
lb
ai
and
the
inhalation
exposure
potential
is
0.0012
mg/
lb
ai.
Because
the
toxicity
endpoint
is
the
same
for
both
routes
of
exposure
and
the
dermal
absorption
is
assumed
to
be
100%
in
the
absence
of
data,
the
combined
dose
is
0.0242
mg/
lb
ai.
The
Scenario
13
dermal
exposure
potential
for
the
groundboom
applicator
wearing
long
pants
and
a
long­
sleeved
shirt
is
0.014
mg/
lb
ai
and
the
inhalation
exposure
potential
is
0.00074
mg/
lb
ai.
The
combined
dose
is
0.0147
mg/
lb
ai.

The
treatment
of
80
acres/
day
requires
3.2
lb
a.
i.
The
daily
dose
for
a
70­
kg
individual
and
the
resultant
MOE
based
on
the
NOEL
of
13.8
mg/
kg/
day
is
calculated
as
follows:

mixer/
loader
groundboom
application
(
80
acres/
day)
dialy
exposure
estimate
=
0.0242
mg/
lb
ai
x
3.2
lb
ai/
day
÷
70
kg
=
0.0011
mg/
kg/
day
MOE
=
13.8
mg/
kg/
day
÷
0.0011
mg/
kg/
day
=
13,000
applicator
groundboom
application
(
80
acres/
day)
daily
exposure
estimate
=
0.0147
mg/
lb
ai
x
3.2
lb
ai/
day
÷
70
kg
=
0.00067
mg/
kg/
day
MOE
=
13.8
mg/
kg/
day
÷
0.00067
mg/
kg/
day
=
21,000
Handspray
Applications:
The
exposure
to
LCOs
and
other
applicators
applying
isoxadifen­
ethyl
to
to
residential
lawns,
park
turf,
golf
course
greens
and
tees,
and
similar
sites
by
hand
held
spray
gun
application
is
based
on
exposure
data
developed
by
the
ORETF.
Aventis
is
a
member
of
the
ORETF.
ORETF
Study
OMA0051
is
an
integrated
report
that
contains
ORETF
Study
OMA002
that
specifically
deals
with
LCO
exposure.
OMA002,
Exposure
of
Professional
Lawn
Care
Workers
During
the
Mixing
and
Loading
of
Dry
and
Liquid
Formulations
and
the
Liquid
Application
of
Turf
Pesticides
Utilising
a
Surrogate
Compound,
has
also
been
submitted
to
the
Agency
by
ORETF.
The
objective
of
the
study
was
to
obtain
an
assessment
of
the
potential
dermal
and
inhalation
exposure
to
professionals
applying
liquid
sprays
to
turf.
2
Determination
of
Dermal
and
Inhalation
Exposure
to
Reentry
Workers
During
Harvesting
in
Sod.
13
June
2001.
MRID
No.
45432303.

Page
28
of
30
Fifteen
replications
of
LCOs
mixing/
loading
and
applying
flowable
liquids
by
hand­
held
spray
guns
were
monitored.
Dermal
exposure
was
monitored
using
whole
body
dosimeters
worn
under
long
pants
and
long­
sleeved
shirts,
hand
washes,
and
face
wipes.
Residues
from
the
inner
whole
body
dosimeters,
the
hands,
and
face
were
quantified
to
estimated
actual
dermal
exposure.
Inhalation
exposure
was
monitored
using
personal
air
sampling
pumps.
Each
replication
consisted
of
the
LCO
handling
approximately
2.3
kg
ai
during
a
work
cycle
that
treated
approximately
2.5
acres.
The
geometric
mean
dermal
and
inhalation
exposures
for
an
LCO
mixing,
loading,
and
applying
a
liquid
formulation
while
wearing
protective
gloves,
long
pants,
and
a
long­
sleeved
shirt
were
0.00511
mg/
kg/
lb
ai
and
0.000018
mg/
kg/
lb
ai,
respectively.
The
geometric
mean
LCO
body
weight
of
the
15
replications
was
82.7
kg.
The
equivalent
dermal
and
inhalation
exposure
in
mg/
lb
ai
is
0.423
mg/
lb
ai
for
dermal
exposure
and
0.0015
mg/
lb
ai.
The
combined
dose
is
0.425
mg/
lb
ai
assuming
100%
dermal
absorption.

The
combined
dermal
and
inhalation
exposure
for
a
professional
handspray
application
that
includes
mixing/
loading
is
0.425
mg/
lb
ai.
The
treatment
of
5
acres/
day
requires
0.2
lb
a.
i.
The
daily
dose
for
a
70­
kg
individual
and
resultant
MOE
based
on
the
NOEL
of
13.8
mg/
kg/
day
is
calculated
as
follows:

mixer/
loader/
applicator
hand
spray
application
(
5
acre/
day)
daily
exposure
estimate
=
0.425
mg/
lb
ai
x
0.2
lb
ai/
day
÷
70
kg
=
0.0012
mg/
kg/
day
MOE
=
13.8
mg/
kg/
day
÷
0.0012
mg/
kg/
day
=
12,000
7.2
Post­
Application
Exposures
and
Assumptions
Sod
Farms:
The
ARTED
Task
Force
study
ARF0352
and
the
resultant
ARTF
database
transfer
coefficients
for
sod
are
used
in
this
assessment.
ARF035
involved
the
application
of
a
pesticide
to
3.3
ha
of
bluegrass
sod.
Work
functions
involved
the
workers
standing
on
the
sod
cutter
beside
the
chute
(
they
worked
in
pairs,
one
on
each
side
of
the
cutter).
As
the
sod
moved
through
the
chute,
the
workers
grabbed
the
sod,
positioned
it
over
the
stack
area,
and
dropped
the
sod
on
the
ground
to
simulate
dropping
it
onto
a
pallet.
Workers
were
monitored
on
the
second,
third,
and
fourth
days
following
the
second
application.
Dermal
exposure
was
monitored
using
whole
body
dosimeters
placed
under
long
pants
and
a
long­
sleeved
shirt.
Face/
neck
wipes
and
hand
washes
were
also
conducted.
Inhalation
exposure
was
monitored
using
personal
air
pumps
drawing
air
at
2.0
litres/
minute.
The
TTRs
were
monitored
using
the
ORETF
SOP
10.
E.
The
dosimeter
was
a
5570
cm2
cotton
cloth.
TTRs
were
collected
14
hours
before
the
first
application,
as
soon
as
possible
after
the
first
and
second
applications
were
dry,
and
on
days
1,
2,
3,
4,
5,
6,
7,
and
14
days
after
the
second
application.
The
three
days
of
reentry
occurred
on
days
2,
3,
and
4
after
the
second
application.

The
day
0
TTRs
after
the
second
application
averaged
0.00087
mg/
cm2.
The
application
rate
was
12.7
kg
ai/
ha
and
the
day
0
TTRs
were
0.69%
of
the
application
rate.
The
TTRs
from
ARF035
is
consistent
with
the
TTRs
established
by
the
ORETF
(
Evaluation
of
Transferable
Turf
Residue
Data
From
Studies
Conducted
or
Purchased
by
the
ORETF,
31­
Oct­
2000).
The
day
0
TTR
value
expressed
as
a
percentage
of
the
application
rate
was
0.62%
based
on
over
100
replications
of
data.
The
ORETF
TTR
data
was
not
used
for
the
post
application
lawn
exposure
assessment
because
the
Jazzercise­
based
TC
of
14,500
cm2/
hr
was
not
determined
concurrently
with
the
turf
TTR
data.
3
Determination
of
Dermal
and
Inhalation
Exposure
to
Reentry
Workers
During
Maintenance
Activities
on
Golf
Courses,
26
Oct
2001.
MRID
No.
4553010.

Page
29
of
30
EPA
has
expressed
concern
that
the
TC
to
TTR
relationship
may
not
be
linear
to
permit
extrapolation
down
to
the
ORETF
TTRs
of
0.62%.
Because
the
sod
TCs
were
determined
concurrently
with
the
TTR
of
0.69%
and
this
TTR
is
similar
to
the
overall
ORETF
TTR
estimate
of
0.62%,
the
ORETF
data
can
be
used
generically
for
isoxadifen­
ethyl
use
as
a
safener
on
sod.
Based
on
the
application
rate
of
45
g
ai/
ha
(
0.45
mg/
cm2)
and
a
day
0
TTR
of
0.62%
of
the
application
rate,
the
day
0
isoxadifen­
ethyl
TTR
estimate
is
0.0000028
mg/
cm2.

The
ARTF
database
was
used
to
obtain
the
TCs
for
use
in
calculating
sod
reentry
exposures.
The
database
was
subset
for
crop
equal
to
sod
and
activity,
foliage
density,
and
crop
height
equal
to
all.
A
total
of
eight
post
application
activities
are
presented.
Four
activities
(
fertilizing,
roll
harvesting,
irrigation,
and
mechanical
weeding)
do
not
require
TCs
and
are
considered
no
contact
activities.
Three
activities
were
clustered
in
cluster
code
DM
and
involved
scouting,
transplanting,
and
hand
weeding.
The
DM
activities
were
derived
from
ARTF
study
ARF
0463.
Despite
the
clustering
of
these
golf
course
activities
in
the
ARTF
database
with
sodfarms
the
work
activities
that
were
monitored
are
not
representative
of
sod
farm
activities.
The
activities
included
the
changing
of
cup
hole
locations
on
greens
by
driving
a
cup
changer
into
the
green
and
drawing
out
a
sod
plug,
removing
the
plastic
cup
from
the
old
hole
and
placing
it
in
the
new
hole,
and
finally
placing
the
sod
plug
in
the
old
hole
and
tamping
it
down
by
hand.
This
activity
is
represented
as
transplanting
in
the
cluster.
Weeding
by
hand
is
represented
by
workers
stooping
or
kneeling
on
the
turf
and
using
a
weeding
tool
to
remove
goose
grass
from
the
turf.
Such
hand
weeding
is
atypical
on
sod
farms.
The
combined
activities
required
five
to
seven
hours.
Because
the
DM
TC
is
derived
from
dermal
exposure
monitored
during
activities
that
do
not
occur
on
sod
farms,
the
TC
of
19,700
cm2/
hr
are
not
considered
valid
for
sod
farm
post
application
exposure
assessment.

The
DH
cluster
activity
of
harvesting
sod
was
obtained
from
the
ARF035
study
and
is
relevant
to
isoxadifen­
ethyl
sod
farm
postapplication
exposure.
A
TC
of
6,180
cm2/
hr
was
established
for
sod
harvesting.
This
harvesting
TC
is
an
upper
bound
estimate
of
TCs
such
as
scouting
and
will
be
used
to
represent
a
full
8­
hour
workday.
Based
on
a
day
0
TTR
of
0.0000028
mg/
cm2,
a
TC
of
6,180
cm2/
hr,
an
8­
hour
duration,
and
a
70­
kg
body
weight,
the
daily
dermal
exposure
from
harvesting
sod
on
day
0
is
calculated
as
follows:

post­
application
exposure
sod
farm
daily
exposure
estimate=
0.0000028
mg/
cm2
x
6,180
cm2/
hr
x
8
hr/
day
÷
70
kg
=
0.00020
mg/
kg/
day
MOE
=
13.8
mg/
kg/
day
÷
0.002
mg/
kg/
day
=
6900
The
MOE
of
6900
supports
a
sod
farm
restricted
entry
interval
of
12
hours
for
harvesting.

Golf
Course:
The
ARTF
database
was
used
to
obtain
the
TCs
for
use
in
calculating
golf
course
reentry
exposures.
The
database
was
subset
for
crop
equal
to
golf
course
and
activity,
foliage
density,
and
crop
height
equal
to
all.
A
total
of
nine
post
application
activities
are
presented.
Five
activities
(
aerating,
fertilizing,
seeding,
irrigation,
and
mechanical
weeding)
do
not
require
TCs
and
are
considered
no
contact
activities.
Four
activities
were
clustered
in
cluster
code
DM
and
involved
maintenance,
scouting,
transplanting,
and
hand
weeding.
The
DM
activities
were
derived
from
ARTF
study
ARF
046.
The
activities
included
the
changing
of
cup
hole
locations
on
greens
by
Page
30
of
30
driving
a
cup
changer
into
the
green
and
drawing
out
a
sod
plug,
removing
the
plastic
cup
from
the
old
hole
and
placing
it
in
the
new
hole,
and
finally
placing
the
sod
plug
in
the
old
hole
and
tamping
it
down
by
hand.
Weeding
by
hand
is
represented
by
workers
stooping
or
kneeling
on
the
turf
and
using
a
weeding
tool
to
remove
goose
grass
from
the
turf.
Finally,
the
workers
were
involved
in
mowing
the
tees,
fairways,
and
greens.
The
combined
activities
required
five
to
seven
hours.
The
DM
TC
is
19,700
cm2/
hr.
Based
on
a
day
0
TTR
of
0.0000028
mg/
cm2,
a
TC
of
19,700
cm2/
hr
and
an
eight­
hour
exposure
duration,
the
daily
exposure
and
resultant
MOE
to
a
70­
kg
golf
course
worker
is
calculated
as
follows:

post­
application
exposure
sod
farm
daily
exposure
estimate
=
0.0000028
mg/
cm2
x
19,700
cm2/
hr
x
8
hr/
day
÷
70
kg
=
0.0063
mg/
kg/
day
MOE
=
13.8
mg/
kg/
day
÷
0.0063
mg/
kg/
day
=
2200
The
MOE
of
2200
supports
a
non­
WPS
reentry
statement
permitting
maintenance
activities
after
sprays
have
dried.

7.3
Restricted
Entry
Intervals
(
REIs)

A
12­
hour
REI
is
appropriate
for
isoxadifen­
ethyl.

7.4
Incidents
A
search
of
OPP's
REFS
Incident
Data
Reporting
System
revealed
no
recorded
incidents
for
isoxadifen­
ethyl.

8.0
TOXICOLOGICAL,
RESIDUE
CHEMISTRY,
and
OCCUPATIONAL/
RESIDENTIAL
DATA
DEFICIENCIES
8.1
Toxicology
°
The
lack
of
a
28­
day
inhalation
toxicity
study
has
been
identified
by
HIARC
as
a
data
gap
for
isoxadifen­
ethyl.
Based
upon
the
low
acute
inhalation
toxicity
(
acute
inhalation
toxicity
category
IV),
low
vapor
pressure
(
1.65
x
10
­
8
mm
Hg),
and
since
the
inhalation
MOEs
resulting
from
the
proposed
turf
use
and
the
registered
corn
and
rice
uses
were
>
1000
(
7,800­
3,300,000;
i.
e.
>
10x
the
LOC),
HED
will
not
require
the
submission
of
the
28­
day
inhalation
study
in
support
of
the
turf
or
rice/
corn
petitions
(
TXR
No
0052240,
M.
Dow,
18­
Nov­
2003).

8.2
Residue
Chemistry
°
multiresidue
testing
of
AE
C637375
8.3
Occupational
Exposure
°
none
cc:
T.
Bloem,
PV
Shah,
Mark
Dow
RDI:
RAB1
(
12­
Nov­
2003)
T.
Bloem:
806R:
CM#
2:(
703)
605­
0217:
7509C:
RAB1
