Document ID: EPA-HQ-OPP-2005-0536-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-21T04:00Z

Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
1
Interregional
Research
Project
Number
4
(
IR­
4)

PP#
3E6775
PETITION
SUMMARY.
EPA
has
received
a
pesticide
petition
(
3E6775)
from
IR­
4,
681
US
Highway
#
1
South,
North
Brunswick,
NJ
08902
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.535
by
establishing
a
tolerance
for
the
residues
of
fluroxypyr
MHE
and
its
metabolite
fluroxypyr
(
expressed
as
combined
residues
of
total
fluroxypyr)
in
or
on
onion,
dry
bulb
at
0.03
parts
per
million
(
ppm);
garlic,
bulb
at
0.03
ppm
and
shallot,
bulb
at
0.03
ppm.
Dow
AgroSciences,
9330
Zionsville
Road,
Indianapolis,
IN
46268
is
the
manufacturer
and
basic
registrant
of
fluroxypr.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
and
Animal
Metabolism.
The
nature
of
the
residue
in
plants
and
animals
is
adequately
understood
for
the
purpose
of
this
tolerance.
Based
on
the
findings
from
these
studies,
the
residues
of
concern
in
plants
and
animal
commodities
are
the
parent,
fluroxypyr
1­
methylheptly
ester
(
MHE)
and
its
metabolite
fluroxypyr,
free
and
conjugated.
Therefore,
the
tolerance
expression
is
the
combined
residues
of
total
fluroxypyr.

2.
Analytical
Method.
Adequate
enforcement
method
for
the
combined
residues
of
total
fluroxypyr
is
available
to
enforce
the
tolerance
expression
in
or
on
food.
The
analytical
method
uses
capillary
gas
chromatography
and
mass
selective
detection
(
GC­
MSD)
with
limits
of
quantitation
(
LOQ)
of
0.01
ppm.
Fluroxypyr
has
also
been
tested
through
the
Food
and
Drug
Administration
(
FDA),
Multi­
residue
Methodology,
Protocols
C,
D,
and
E.
The
results
have
been
published
in
the
FDA
Pesticide
Analytical
Manual,
Volume
1.

3.
Magnitude
of
Residues.
Geographically
representative
field
trials
with
Vista*,
a
soluble
concentrate
formulation
containing
fluroxypyr
MHE,
was
conducted
to
support
the
proposed
tolerance
for
onion
(
dry
bulb).
The
results
of
the
field
trials
indicate
that
the
residues
will
not
exceed
the
proposed
tolerance
of
0.03
ppm
in
or
on
onion
(
dry
bulb).

B.
Toxicological
Profile
1.
Acute
toxicity.
Fluroxypyr
MHE
has
low
acute
toxicity.
The
rat
oral
LD50
is
>
5000
mg/
kg,
the
rabbit
dermal
LD50
is
>
2000
mg/
kg,
and
the
rat
inhalation
LC50
is
>
1.0
mg/
l
(
1000
mg/
cubic
meter).
In
addition,
fluroxypyr
MHE
is
not
a
skin
sensitizer
in
guinea
pigs,
has
no
dermal
irritation
in
rabbits,
and
shows
mild
ocular
irritation
in
rabbits.
The
end
use
formulation
of
fluroxypyr
MHE
has
a
similar
low
acute
toxicity
profile.
Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
2
2.
Genotoxicty.
Short
term
assays
for
genotoxicity
consisting
of
a
bacterial
reverse
mutation
assay
(
Ames
test),
an
in
vitro
assay
for
cytogenetic
damage
using
the
Chinese
hamster
ovary
cells,
an
in
vitro
chromosomal
aberration
assay
using
rat
lymphocytes,
and
an
in
vivo
cytogenetic
assay
in
the
mouse
bone
marrow
(
micronucleus
test)
have
been
conducted
with
fluroxypyr
MHE.
These
studies
show
a
lack
of
genotoxicity.
In
addition,
short
term
assays
for
genotoxicity
consisting
of
an
Ames
metabolic
activation
test,
possible
induction
of
point
mutations
at
the
HGPRT­
Locus
of
Chinese
hamster
ovary
cells,
in
vivo
and
in
vitro
chromosomal
aberrations
in
the
Chinese
hamster
ovary
cells,
unscheduled
DNA
synthesis
in
human
embryonic
cells,
and
an
assay
in
mouse
lymphoma
cells
have
been
conducted
with
fluroxypyr.
These
studies
also
show
a
lack
of
genotoxicity.

3.
Reproductive
and
Developmental
Toxicity.
Developmental
studies
in
rats
and
rabbits
were
conducted
with
both
fluroxypyr
MHE
and
fluroxypyr.
Studies
with
fluroxypyr
MHE
showed
maternal
and
fetal
NOELs
of
300
mg/
kg/
day
(
rat)
and
500
mg/
kg/
day
(
rabbit).
Studies
with
fluroxypyr
showed
NOAELs
in
the
rat
of
250
mg/
kg/
day
for
maternal
effects
and
500
mg/
kg/
day
for
fetal
effects
and
a
NOEL
in
the
rabbit
of
250
mg/
kg/
day
for
both
maternal
and
fetal
effects.
These
studies
show
that
fluroxypyr
and
fluroxypyr
MHE
are
not
teratogenic
nor
will
they
interfere
with
in
utero
development.
Two
multi­
generation
reproduction
studies
were
conducted
with
fluroxypyr
in
rats.
The
first
in
Wistar
rats
showed
no
effect
on
fertility
or
reproductive
performance
and
had
a
NOAEL
of
500
mg/
kg/
day
(
highest
dose
tested).
The
second
study
in
Sprague­
Dawley
rats
showed
a
parental
NOEL
for
systemic
effects
of
100
mg/
kg/
day
in
male
rats
and
500
mg/
kg/
day
in
female
rats.
The
NOEL
for
reproductive
effects
was
750
mg/
kg/
day
for
males
and
1000
mg/
kg/
day
for
females
(
highest
dose
tested).
The
NOEL
for
neonatal
effects
was
500
mg/
kg/
day.

4.
Subchronic
Toxicity.
Fluroxypyr
MHE
showed
a
NOEL
of
1000
mg/
kg/
day
in
a
90­
day
rat
dietary
study
and
a
21­
day
rabbit
dermal
study.
Ninety­
day
feeding
studies
with
fluroxypyr
showed
NOELs
of
80
mg/
kg/
day
(
Wistar
rats),
700
mg/
kg/
day
(
Fischer
344
rats),
1342
mg/
kg/
day
(
male
mice),
and
1748
mg/
kg/
day
(
female
mice).
In
a
4­
week
dietary,
range
finding
study
with
fluroxypyr
in
dogs
the
NOEL
found
was
>
50
mg/
kg/
day.

5.
Chronic
Toxicity.
Based
on
chronic
testing
with
fluroxypyr
in
the
mouse,
dog,
and
rat
(
two
studies),
a
reference
dose
(
RfD)
of
0.8
mg/
kg/
day
is
proposed
for
fluroxypyr
and
fluroxypyr
MHE.
The
RfD
has
incorporated
a
100­
fold
safety
factor
to
the
NOEL
found
in
the
rat
chronic
test.
NOELs
found
in
the
chronic
dietary
studies
are
as
follows:
150
mg/
kg/
day
(
dog),
300
mg/
kg/
day
(
mouse),
80
mg/
kg/
day
(
Wistar
rats),
100
mg/
kg/
day
(
male
Fischer
344
rats),
and
500
mg/
kg/
day
(
female
Fischer
344
rats).

6.
Animal
Metabolism.
Both
fluroxypyr
and
fluroxypyr
MHE
have
been
evaluated
in
rat
metabolism
studies.
In
summary,
these
studies
show
that
fluroxypyr
MHE
is
rapidly
hydrolyzed
and
the
fate
of
the
hydrolysis
products,
fluroxypyr
and
1­
methylheptanol,
are
independent
of
whether
they
were
given
as
the
ester
or
the
acid.
Fluroxypyr,
per
se,
was
extensively
absorbed
and
rapidly
excreted
principally
unchanged
in
the
urine;
1­
Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
3
methylheptanol
also
was
rapidly
absorbed
and
rapidly
eliminated.
Repeated
administration
of
fluroxypyr
MHE
was
not
associated
with
accumulation
in
tissues.
Also,
the
metabolism
and
pharmacokinetics
of
1­
methylheptanol
are
comparable
to
that
of
the
methylheptyl
portion
of
fluroxypyr
MHE.

7.
Metabolite
Toxicology.
Administration
of
fluroxypyr,
as
the
acid
or
methylheptyl
ester,
in
a
variety
of
toxicological
studies
has
produced
similar
effects.
The
principal
response
to
sufficiently
high
dosages,
whether
administered
over
the
short­
term
or,
in
some
cases,
over
a
lifetime,
was
nephrosis.
Fluroxypyr
is
an
organic
acid
that
is
actively
excreted
into
the
urine
by
the
kidney.
Thus,
the
target
organ
and
dose
response
relationship
for
fluroxypyr
toxicity
is
entirely
consistent
with
the
data
on
the
toxicokinetics
of
fluroxypyr.
Metabolism
studies
have
shown
that
fluroxypyr
MHE
is
rapidly
and
completely
hydrolyzed
to
fluroxypyr
acid
and
methylheptanol.

8.
Endocrine
Disruption.
There
is
no
evidence
to
suggest
that
fluroxypyr
and
fluroxypyr
MHE
have
an
effect
on
any
endocrine
system.

C.
Aggregate
Exposure
1.
Dietary
Exposure.

i.
Food.
Conservative
dietary
risk
assessments
(
Tier
I)
were
conducted
for
acute,
short­
term
and
chronic
exposures.
The
dietary
exposure
assessments
were
based
on
assumptions
that
100%
of
the
crops
were
treated
and
the
residues
were
present
at
the
tolerance
levels
as
established
in
40
CFR
180.535
for
fluroxypyr.
Included
in
these
assessments
are
the
tolerance
of
0.03
ppm
for
onion
(
dry),
as
proposed
in
this
petition,
together
with
other
proposed/
revised
tolerances
for
corn,
sorghum,
milk
and
meat
products
(
Federal
Register/
Vol.
68,
No.
93,
May
14,
2003).
In
conducting
the
assessments,
Dow
AgroSciences
used
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
,
Version
7.87,
Exponent)
software
with
the
food
commodity
intake
database
which
incorporates
food
consumption
data
as
reported
by
respondents
in
the
USDA
1994­
1198
nationwide
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII).

Acute
dietary
risk
was
assessed
using
an
acute
RfD
of
1.25
mg/
kg/
day,
based
on
a
maternal
NOAEL
of
125
mg/
kg/
day
from
a
rat
developmental
toxicity
study
and
an
uncertainty
factor
of
100
(
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variation).
EPA
previously
established
the
maternal
NOAEL
for
this
study
at
125
mg/
kg/
day
and
it
was
used
here
for
a
very
conservative
assessment.
There
was
no
indication
of
increased
susceptibility
in
young
animals
to
pre­
or
postnatal
exposure
to
fluroxypyr
in
the
toxicology
studies.
Therefore,
an
FQPA
additional
safety
factor
for
infants
and
children
was
not
included
in
this
assessment.
Acute
dietary
exposures
at
the
95th
percentile
are
estimated
to
be
0.010433
mg/
kg/
day
for
the
general
U.
S.
population,
0.004741
mg/
kg/
day
for
females
(
13­
50
Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
4
years
old)
and
0.023735
mg/
kg/
day
for
children
(
1­
6
years
old)
which
occupy
0.83%,
0.38%
and
1.9%
of
the
acute
RfD,
respectively.
Adverse
effects
are
not
expected
for
exposures
occupying
less
than
100%
of
the
RfD.
Therefore,
acute
dietary
exposure
and
risk
are
well
within
acceptable
levels.

To
assess
short­
term
dietary
exposure
and
risk,
the
chronic
dietary
estimates
along
with
the
short­
term
oral
NOAEL
were
used.
The
90­
day
dietary
study
in
rat
with
a
NOAEL
of
80
mg/
kg/
day
was
chosen
for
establishing
a
short­
term
oral
toxicity
endpoint
since
this
study
provided
the
lowest
NOAEL
of
the
90­
day
studies
conducted
with
fluroxypyr
MHE.
The
short­
term
margin
of
exposure
(
MOE)
was
calculated
by
dividing
the
short­
term
oral
NOAEL
(
80
mg/
kg/
day)
by
the
estimated
chronic
dietary
exposure
(
DEEM
analysis).
The
estimated
dietary
exposures
were
0.003122
mg/
kg/
day
for
the
U.
S.
population
and
0.010629
mg/
kg/
day
for
children
1­
6
years
old.
The
resulting
MOEs
of
25,625
for
U.
S.
population
and
7,527
for
children
1­
6
years
old
were
substantially
greater
than
100,
therefore,
the
short­
term
risk
is
well
within
the
acceptable
levels.

Chronic
dietary
risk
was
assessed
using
a
chronic
RfD
of
0.80
mg/
kg/
day,
based
on
a
NOAEL
of
80
mg/
kg/
day
from
a
combined
chronic
toxicity
and
carcinogenicity
study
in
rats
and
an
uncertainty
factor
of
100
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation).
The
chronic
dietary
exposure
was
estimated
to
be
0.003122
mg/
kg/
day
for
the
general
U.
S.
population
which
occupies
0.4%
of
the
chronic
RfD.
Children
1­
2
years
old,
the
population
subgroup
with
the
highest
potential
exposure,
were
estimated
to
have
a
chronic
dietary
exposure
of
0.013539
mg/
kg/
day
which
utilizes
1.7%
of
the
chronic
RfD.
Adverse
effects
are
not
expected
for
exposures
utilizing
less
than
100%
of
the
RfD,
therefore,
chronic
dietary
exposure
and
risk
for
the
general
U.
S.
population
and
children
are
well
within
the
acceptable
levels.

ii.
Drinking
Water.
There
are
no
established
Maximum
Contaminant
Levels
for
residues
of
fluroxypyr
in
drinking
water
and
health
advisory
levels
for
fluroxypyr
in
drinking
water
have
not
been
established.

Guidance
from
EPA
has
indicated
that
Tier
1
screening
level
models,
such
as
GENEEC
and
SCI­
GROW,
maybe
used
to
estimate
upper­
bound
pesticide
residues
in
surface
water
and
ground
water
when
assessing
potential
exposure
through
drinking
water.
Estimated
environmental
concentrations
(
EEC)
of
pesticide
in
surface
water
or
ground
water
are
then
compared
to
a
drinking
water
level
of
comparison
(
DWLOC).
DWLOC
is
not
a
regulatory
standard
for
drinking
water
but
a
theoretical
upper
limit
on
a
pesticide's
concentration
in
drinking
water
in
light
of
total
aggregate
exposure
to
a
pesticide
in
food
and
from
residential
uses.
DWLOC
determines
how
much
of
the
acceptable
exposure
(
PAD)
is
available
for
exposure
through
drinking
water.
In
calculating
DWLOC,
default
values
for
body
weights
and
water
consumption
were
used:
2L/
70
kg
adult
male,
2L/
60
kg
adult
female
and
Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
5
1L/
10
kg
child.

EPA
has
indicated
that
peak
concentrations
of
pesticide
in
surface
water
should
be
used
in
an
acute
assessment
for
comparison
with
DWLOC
values.
The
estimated
peak
concentration
of
fluroxypyr
in
surface
water
using
GENEEC
is
20.88
µ
g/
L.
For
ground
water,
the
estimated
concentration
by
SCI­
GROW
is
0.16
µ
g/
L.
As
shown
below
the
EECs
in
surface
water
and
ground
water
are
substantially
below
the
acute
DWLOC,
therefore,
aggregate
acute
exposure
is
not
expected
to
exceed
100%
of
the
aPAD.

Population
Subgroup
aPAD
(
mg/
kg/
d
ay)
Dietary
Exposure
(
mg/
kg
bw/
day)
Surface
Water
(
µ
g/
L)
Ground
Water
(
µ
g/
L)
DWLOC
(
µ
g/
L)

U.
S.
Population
(
general)
1.25
0.010433
20.88a
0.16
43385
Females
(
13­
50
yrs
old)
1.25
0.004741
20.88a
0.16
37358
Children
(
1­
6
yrs
old)
1.25
0.023735
20.88a
0.16
12263
a
Estimated
peak
concentration
EPA
has
indicated
that
the
56­
day
value
from
GENEEC
should
be
divided
by
3
for
comparison
to
the
chronic
DWLOC
values.
The
estimated
56­
day
day
concentration
of
fluroxypyr
is
7.08
µ
g/
L
by
GENEEC,
therefore,
the
surface
water
concentration
used
in
this
assessment
is
2.36
µ
g/
L.
For
ground
water,
the
estimated
concentration
by
SCI­
GROW
is
0.16
µ
g/
L.
As
shown
below
the
EECs
in
surface
water
and
ground
water
are
substantially
below
the
chronic
DWLOC,
therefore,
aggregate
chronic
exposure
is
not
expected
to
exceed
100%
of
the
cPAD.

Population
Subgroup
cPAD
(
mg/
kg/
d
ay)
Dietary
Exposure
(
mg/
kg
bw/
day)
Surface
Water
(
µ
g/
L)
Ground
Water
(
µ
g/
L)
DWLOC
(
µ
g/
L)

U.
S.
Population
(
adults)
0.80
0.003122
2.36a
0.16
27891
Females
(
13­
50
yrs
old)
0.80
0.001872
2.36a
0.16
23944
Children
(
1­
2
yrs
old)
0.80
0.013539
2.36a
0.16
7865
Children
(
1­
6
yrs
old)
0.80
0.010629
2.36a
0.16
7894
a
Concentration
at
56­
day
(
7.08
µ
g/
L)
divided
by
3.

For
short­
term
exposure,
potential
residential
exposure
resulting
from
fluroxypyr
use
on
turf
was
included
when
calculating
DWLOC
values
for
adults
and
children
(
1­
6
years
old).
The
food
and
residential
aggregated
results
indicated
MOEs
of
6443
and
5021
for
the
general
U.
S.
population
and
children
(
1­
6
years),
respectively.
These
aggregate
MOEs
do
not
exceed
the
Agency's
level
of
concern
for
aggregate
Fluroxypyr
Notice
of
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EMB/
09/
2003
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6
exposure
to
food
and
residential
uses.
In
addition,
the
EECs
in
surface
water
and
ground
water
are
substantially
below
the
short­
and
intermediate­
term
DWLOCs
as
shown
below.

Population
Subgroup
Aggregate
MOEa
Aggregate
Level
of
Concern
Surface
Water
(
µ
g/
L)
Ground
Water
(
µ
g/
L)
DWLOC
(
µ
g/
L)

U.
S.
Population
(
general)
6443
100
2.36
0.16
27450
Children
(
1­
6
yrs
old)
5021
100
2.36
0.16
7843
a
Aggregate
MOE
(
Food
+
Residential)

2.
Non­
Dietary
Exposure.
Non­
occupational,
Non­
Dietary
(
Residential)
Exposure
and
Risk.
The
proposed
use
of
fluroxypyr
on
residential
turf
presents
the
potential
for
nonoccupational
non­
dietary
(
or
residential)
exposure.
Transferable
foliar
residue
data
from
a
fluroxypyr
study
on
turf
was
used
instead
of
default
residue
values.

Post­
application
dermal
exposure
for
adults
and
toddlers
was
estimated
for
the
day
of
application
(
day
0)
since
the
exposure
potential
is
greatest
at
this
time.
Transferable
residue
of
fluroxypyr
from
turf
was
found
to
range
from
0.03
to
0.74%
(
used
as
a
high
end
estimate)
of
the
fluroxypyr
applied
and
to
dissipate
with
a
half­
life
ranging
from
1.4
to
2.5
days.

Homeowners
may
be
exposed
to
fluroxypyr
during
application
to
turf
and
also
may
have
dermal
exposure
due
to
post­
application
activity
on
the
treated
turf.
Homeowner
exposure
during
the
application
of
fluroxypyr
to
turf
includes
both
dermal
and
inhalation
exposure.
Surrogate
dermal
and
inhalation
exposure
data
from
Pesticide
Handlers
Exposure
Database
(
PHED
V1.1)
was
used
in
estimating
applicator
exposure.
The
PHED
surrogate
data
used
to
estimate
exposure
assumes
residential
applicator
attire
to
include
short
pants,
shortsleeve
shirt,
and
no
gloves.
The
applicator
exposure
estimate
was
based
on
a
broadcast
application
using
a
garden
hose
end
sprayer.
Applicator
dermal
and
inhalation
exposure
was
estimated
to
be
0.0986
mg/
kg/
day
and
0.00003
mg/
kg/
day,
respectively.

Adult
post­
application
dermal
exposure
from
treated
turf
on
the
day
of
application
was
estimated
to
be
0.0172
mg/
kg/
day.
The
combined
dermal
exposure
from
application
along
with
post­
application
activity
is
0.1158
mg/
kg/
day
(
0.0986
mg/
kg/
day
+
0.0172
mg/
kg/
day).
Oral
post­
application
exposure
is
not
expected
for
adults
and
was
not
included
in
this
assessment.
The
MOEs
for
dermal
exposure
is
8635
and
for
inhalation
exposure
2666667.
These
MOEs
are
substantially
greater
than
100,
indicating
that
risk
from
these
potential
exposures
is
well
within
an
acceptable
level.
Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
7
Consistent
with
the
scenario
described
above
for
the
general
adult
population,
female
adult
homeowners
may
experience
exposure
to
fluroxypyr
during
application
to
turf
as
well
as
from
post­
application
exposure.
Female
applicator
dermal
and
inhalation
exposure
was
estimated
to
be
0.115
mg/
kg/
day
and
0.00004
mg/
kg/
day,
respectively.
Additionally,
female
adults
may
also
experience
post­
application
dermal
exposure
from
treated
turf
on
the
day
of
application.
Post­
application
dermal
exposure
for
females
was
estimated
to
be
0.0201
mg/
kg/
day.
Since
dermal
absorption
is
assumed
to
be
100%
and
since
both
dermal
and
inhalation
exposure
are
being
evaluated
against
the
same
toxicity
endpoint,
total
potential
exposure
from
fluroxypyr
use
on
turf
can
be
estimated
by
simply
adding
the
dermal
and
inhalation
exposure.
The
combined
exposure
is
0.13514
mg/
kg/
day
(
0.115
mg/
kg/
day
+
0.00004
mg/
kg/
day
+
0.0201
mg/
kg/
day).
Using
a
NOEL
of
125
mg/
kg/
day,
the
MOE
is
calculated
to
be
925
(
125
mg/
kg/
day
/
0.13514
mg/
kg/
day).
The
MOE
for
female
adults,
as
a
result
of
potential
dermal
and
inhalation
exposure
from
residential
use
of
fluroxypyr
on
turf
is
well
above
100,
indicating
that
the
risk
is
within
acceptable
levels.

Golfers
may
have
dermal
exposure
to
fluroxypyr
due
to
post­
application
activity
on
the
treated
turf.
Dermal
exposure
for
adult
golfers
was
estimated
on
the
day
of
treatment
(
day
0)
to
provide
a
high­
end
estimate
of
exposure.
Exposure
was
estimated
based
on
a
transfer
coefficient
of
500
cm2/
hr
(
1)
and
an
exposure
time
of
4
hours.
Exposure
was
estimated
to
be
0.001186
mg/
kg/
day.
A
MOE
of
843,170
was
calculated
based
on
an
assumption
of
100%
dermal
absorption
and
a
NOEL
of
1000
mg/
kg/
day.
Given
a
MOE
of
three
orders
of
magnitude
greater
than
100,
risk
is
well
within
acceptable
levels.

Potential
exposure
for
female
golfers
was
estimated
to
be
0.001383
mg/
kg/
day.
A
MOE
of
90,383
was
calculated
based
on
an
assumption
of
100%
dermal
absorption
and
a
NOEL
of
125
mg/
kg/
day.
The
MOE
is
substantially
greater
than
100,
indicating
that
risk
is
well
within
acceptable
levels.

Toddlers
may
have
exposure
to
due
to
post­
application
activity
on
treated
turf.
When
a
pesticide
in
liquid
formulation
is
applied
to
turfgrass,
toddlers
may
experience
postapplication
exposure
through
dermal
exposure
and
also
through
oral
exposure
due
to
handto
mouth
transfer
of
pesticide
residue,
ingestion
of
treated
turfgrass
and
incidental
ingestion
of
soil
from
treated
areas.

Toddler
post­
application
dermal
exposure
from
treated
turf
on
the
day
of
application
was
estimated
to
be
0.0288
mg/
kg/
day.
Oral
exposure
due
to
hand­
to­
mouth
transfer
of
residues
was
estimated
to
be
0.0011
mg/
kg/
day.
Oral
exposure
due
to
ingestion
of
treated
grass
was
estimated
to
be
0.0019
mg/
kg/
day.
Combined
oral
exposure
from
hand­
to­
mouth
transfer
of
residues
and
ingestion
of
treated
grass
is
0.0030
mg/
kg/
day
(
0.0011
mg/
kg/
day
+
0.0019
mg/
kg/
day).
The
MOE
for
dermal
exposure
is
34,722
and
oral
exposure
is
26,667,
both
of
them
well
above
100,
indicating
that
risk
is
well
within
acceptable
levels.

Use
of
fluroxypyr
on
turf
results
in
potential
short­
term
residential
exposure
for
adults
and
children.
Potential
short­
term
dietary
and
residential
exposures
were
combined
into
Fluroxypyr
Notice
of
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EMB/
09/
2003
Page
8
aggregate
Margin
of
Exposure
(
MOE)
values.
Potential
exposure
through
drinking
water
was
not
included
in
the
aggregate
MOEs,
but
was
evaluated
in
aggregate
through
use
of
a
DWLOC
calculated
for
short­
term
exposure.
The
aggregate
MOEs
for
adults
and
toddlers
ranged
from
906
to
29,335,
but
all
were
well
above
100,
indicating
an
adequate
margin
of
safety.
Additionally,
the
short­
term
DWLOCs
for
toddlers
and
adults
were
over
3,000­
fold
greater
than
potential
fluroxypyr
residues
in
drinking
water
predicted
by
conservative
screening
level
models.
Therefore,
aggregate
short­
term
exposure
and
risk
for
children
and
adults
are
expected
to
be
well
within
acceptable
levels.

D.
Cumulative
Effects
The
potential
for
cumulative
effects
of
fluroxypyr
MHE
and
fluroxypyr
and
other
substances
that
have
a
common
mechanism
of
toxicity
is
also
considered.
There
is
no
reliable
information
to
indicate
that
toxic
effects
produced
by
fluroxypyr
MHE
and
fluroxypyr
would
be
cumulative
with
those
of
any
other
pesticide
chemical.
Thus,
it
is
appropriate
to
consider
only
the
potential
risks
of
fluroxypyr
MHE
and
fluroxypyr
in
an
aggregate
exposure
assessment.

E.
Safety
Determination
1.
U.
S.
Population.
Acute
dietary
exposure
for
the
general
U.
S.
population
and
females
(
13­
50
years
old)
to
residues
of
fluroxypyr
from
current
and
proposed
uses
were
estimated
to
occupy,
respectively,
0.83
and
0.38%
of
the
acute
PAD.
Additionally,
the
acute
DWLOC
was
calculated
to
be
over
1,700
fold
greater
than
potential
fluroxypyr
residue
in
drinking
water
predicted
by
conservative
screening
level
models.
Thus,
the
aggregated
acute
exposure
to
fluroxypyr
resulting
from
current
and
proposed
uses
is
well
within
the
acceptable
levels
of
risk.

Chronic
dietary
exposure
for
the
general
U.
S.
population
and
females
(
13­
50
years
old)
to
residues
of
fluroxypyr
from
current
and
proposed
uses
were
estimated
to
occupy,
respectively,
0.4%
and
0.2%
of
the
chronic
PAD.
Furthermore,
the
chronic
DWLOC
was
calculated
to
be
over
10,000
fold
greater
than
potential
fluroxypyr
residue
in
drinking
water
predicted
by
conservative
screening
level
models.
Thus,
the
aggregated
acute
exposure
to
fluroxypyr
resulting
from
current
and
proposed
uses
is
well
within
the
acceptable
levels
of
risk.

Use
of
fluroxypyr
on
turf
results
in
potential
short­
and
intermediate­
term
exposures.
Potential
dietary
and
residential
exposures
were
combined
into
an
aggregate
MOE
value,
which
was
calculated
to
be
6,423
for
adult
U.
S.
population.
The
aggregate
MOE
is
well
above
100,
indicating
risk
is
well
within
acceptable
levels.

Thus,
based
on
the
completeness
and
reliability
of
the
toxicity
data
and
the
conservative
exposure
assessment,
it
is
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
U.
S.
population
from
acute
aggregate,
short­
and
intermediate­
term
or
Fluroxypyr
Notice
of
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EMB/
09/
2003
Page
9
chronic
aggregate
exposures
to
fluroxypyr
residues
from
current
and
proposed
uses.

2.
Infants
and
Children.
FFDCA
Section
408
provides
that
EPA
may
apply
an
additional
safety
factor
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
preand
post­
natal
toxicity
and
the
completeness
of
the
database.
Based
on
the
current
toxicological
data
requirements,
the
database
for
fluroxypyr
MHE
relative
to
pre­
and
post­
natal
effects
for
children
is
complete.
There
were
no
indications
of
neurotoxicity
and
developmental
toxicity
was
not
observed
in
the
absence
of
maternal
toxicity.
It
is
concluded
that
there
is
no
indication
of
increased
sensitivity
of
infants
and
children
relative
to
adults
and
that
an
additional
FQPA
safety
factor
is
not
required.

Acute
dietary
exposure
for
children
(
1­
6
years
old)
to
residues
of
fluroxypyr
from
current
and
proposed
uses
were
estimated
to
occupy
1.9%
of
the
acute
PAD.
Also,
the
acute
DWLOC
was
calculated
to
be
over
500
fold
greater
than
the
potential
residue
of
fluroxypyr
in
drinking
water
predicted
by
conservative
screening
level
models.
Thus,
the
aggregated
acute
exposure
to
fluroxypyr
resulting
from
current
and
proposed
uses
is
well
within
the
acceptable
levels
of
risk.

Chronic
dietary
exposure
to
residues
of
fluroxypyr
from
current
and
proposed
uses
was
estimated
to
occupy
only
1.7%
of
the
chronic
PAD
for
children
1­
2
years
old,
the
population
subgroup
predicted
to
be
most
highly
exposed.
Moreover,
the
DWLOC
was
calculated
to
be
over
3,000
fold
greater
than
potential
fluroxypyr
residue
in
drinking
water
predicted
by
conservative
screening
level
models.

Children
(
1­
6
years
old)
may
experience
short­
term
dermal
and
oral
exposure
to
fluroxypyr
as
a
result
of
post­
application
activities
on
treated
residential
turf.
Additionally,
there
is
the
potential
for
exposure
to
fluroxypyr
through
residue
in
food
and
drinking
water.
Tier
I
assessments
were
conducted
to
develop
very
conservative
estimates
of
potential
exposure
through
residential,
dietary
and
drinking
water
pathways.
Potential
dietary
and
residential
exposures
were
combined
into
an
aggregate
MOE
value.
The
aggregate
MOE
was
5021,
well
above
100,
indicating
risk
is
well
within
acceptable
levels.

Thus,
based
on
the
completeness
and
reliability
of
the
toxicity
data
and
the
conservative
exposure
assessment,
it
is
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
acute
dietary,
short
term
and
chronic
aggregate
exposures
to
fluroxypyr
residues
from
current
and
proposed
uses.

F.
International
Tolerances
There
are
no
Codex
maximum
residue
levels
established
for
residues
of
fluroxypyr
MHE
and
fluroxypyr
on
any
food
or
feed
crop.
Fluroxypyr
Notice
of
Filing
EMB/
09/
2003
Page
10