FILE
NAME:
NOF
Fruiting
Veg
3­
19­
04.
wpd
EPA
Registration
Division
contact:
Joanne
Miller
703­
305­
6224
PP
Number:

Summary
of
Petition
EPA
has
received
a
pesticide
petition
(
insert
petition
number)
from
The
Interregional
Research
Project
No.
4,
North
Brunswick,
N.
J.,
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
180.432
by
establishing
a
tolerance
for
residues
of
the
herbicide
lactofen,
1­(
carboethoxy)
ethyl
5­[
2­
chloro­
4­(
trifluoromethyl)
phenoxy]­
2­
nitrobenzoate,
in
or
on
the
raw
agricultural
commodity
crop
group,
vegetable,
fruiting,
Crop
Group
8
and
okra
at
0.01
ppm.
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
metabolism.
The
nature
of
the
residue
in
plants
is
adequately
understood
based
on
plant
metabolism
studies
conducted
on
cotton,
peanut,
soybean,
and
tomato.
The
regulated
residue
of
concern
is
parent,
lactofen.
2.
Analytical
method.
Adequate
analytical
methodology
is
available
for
detecting
and
measuring
levels
of
lactofen
in
or
on
raw
agricultural
commodities
with
a
limit
of
detection
that
allows
monitoring
of
food
with
residues
at
or
above
the
level
of
the
proposed
tolerances.
The
method,
RM­
28D,
has
been
successfully
radiovalidated
in
conjunction
with
a
tomato
metabolism
study,
has
undergone
a
successful
independent
laboratory
validation
trial,
and
was
successfully
validated
by
the
EPA
Analytical
Chemistry
Laboratory
using
peanut
nutmeats
and
cottonseed.
In
general,
the
analytical
method
has
a
limit
of
detection
of
0.005
ppm
and
a
limit
of
quantitation
of
0.01
ppm
in
crops.
3.
Magnitude
of
residues.
An
adequate
number
of
field
trials
has
been
conducted
on
tomatoes
and
peppers
to
determine
lactofen
residues
resulting
from
the
application
of
lactofen
at
the
maximum
proposed
use
rate.
i.
Tomato:
In
five
(
5)
residue
trials
conducted
in
Florida,
residues
of
lactofen
were
each
<
0.01
ppm
in/
on
tomatoes
harvested
30
days
following
2­
3
applications
of
lactofen
at
0.5
pounds
active
ingredient
per
acre
(
lbs.
a.
i./
A).
All
applications
were
made
either
pre­
transplant
or
via
a
shielded
ground
spray
to
tomato
row
middles
at
14­
67
day
intervals.
In
a
single
residue
trial
conducted
in
Florida,
residues
of
lactofen
were
<
0.01
in/
on
tomatoes
harvested
30
days
following
2
applications
of
lactofen
at
2.5
lbs.
a.
i./
A
(
5x
rate).
Since
no
residues
of
lactofen
were
detected
in
samples
treated
at
the
5x
rate,
a
tomato
processing
study
was
not
conducted.
ii.
Peppers:
In
three
(
3)
residue
trials
conducted
in
Florida
(
2
bell
and
1
non­
bell),
residues
of
lactofen
were
each
<
0.01
ppm
in/
on
peppers
harvested
30
days
following
2
applications
of
lactofen
at
0.5
lbs.
a.
i./
A.
All
applications
were
made
either
pre­
transplant
or
via
a
shielded
ground
spray
to
pepper
row
middles
at
46­
67
day
intervals.
All
these
data
support
the
proposed
tolerance
for
lactofen
in/
on
vegetable,
fruiting,
Crop
Group
8
and
okra
at
0.01
ppm.
No
separate
tolerances
are
needed
for
tomato
processed
commodities.
The
number
of
field
trials
conducted
(
5
tomato,
3
pepper)
and
the
location
of
the
trials
(
northern
Florida)
support
a
product
registration
that
is
geographically
limited
to
the
states
of
Alabama,
Arkansas,
Florida,
Georgia,
Mississippi,
North
Carolina,
South
Carolina,
Tennessee,
and
Virginia.

B.
Toxicological
Profile
1.
Acute
toxicity.
Lactofen
has
very
low
acute
toxicity.
The
acute
oral
LD
50
is
5.96
g/
kg
b.
w.
(
Tox
Category
IV),
the
acute
dermal
LD
50
is
>
2.0
g/
kg
b.
w.
(
Tox
Category
III)
and
the
acute
inhalation
LD
50
is
>
6.3
mg/
L
(
Tox
Category
IV).
Lactofen
is
not
a
skin
sensitizer
but
is
a
very
slight
dermal
irritant.
2.
Genotoxicty.
Lactofen
has
very
little
mutagenic
or
genotoxic
activity.
While
a
positive
mutagenic
response
was
reported
in
one
trial
of
a
Salmonella
typhimurium/
mammalian
microsome
mutagenicity
assay,
this
response
was
not
observed
in
a
repeat
assay.
In
addition,
lactofen
did
not
induce
chromosomal
aberrations,
unscheduled
DNA
synthesis
or
inhibit
DNA
repair.
3.
Reproductive
and
developmental
toxicity.
Reproduction
and
teratology
studies
indicate
that
adverse
effects,
including
embryotoxicity,
occur
only
at
doses
that
are
also
maternally
toxic.
Since
lactofen
causes
effects
only
at
levels
which
also
produce
systemic
toxicity,
the
compound
is
not
a
reproductive
hazard.
i.
Rat
Reproduction:
In
a
2­
generation
reproduction
study
in
rats,
decreased
pup
weight
and
decreased
absolute
and
relative
weights
of
the
spleen
were
first
reported
at
approximately
26.2
mg/
kg/
day
(
based
on
dose
administered
to
the
parental
group).
The
same
dose
level
elicited
mortality
and
decreased
male
fertility
in
the
parental
groups.
The
NOEL
for
both
systemic
and
reproductive
toxicity
in
this
study
was
2.6
mg/
kg/
day.
ii.
Rat
Developmental:
In
the
developmental
toxicity
study
in
rats,
effects
were
observed
at
the
150
mg/
kg/
day
dose
level
consisting
of
decreases
in
fetal
weight
as
well
as
skeletal
abnormalities.
This
dose
level
also
elicited
signs
of
toxicity
in
the
parental
group.
The
NOEL
for
this
study
was
50
mg/
kg/
day.
iii.
Rabbit
Developmental:
Two
developmental
toxicity
studies
were
conducted
in
rabbits.
In
the
first
study,
pregnant
rabbits
were
administered
oral
doses
of
0,
5,
15
or
50
mg/
kg
bw/
day
lactofen
technical
on
days
6­
18
of
gestation.
Maternal
toxicity
(
clinical
signs
and
reduced
weight
gain)
and
developmental
effects
(
increased
embryonic
death,
decreased
litter
size
and
increased
post­
implantation
loss)
were
reported
at
15
and
50
mg/
kg.
The
Agency
concluded
that
the
data
were
insufficient
to
establish
a
clear
NOEL.
A
second
rabbit
developmental
toxicity
study
was
therefore
conducted
in
which
pregnant
rabbits
were
exposed
to
0,
1,
4
or
20
mg/
kg
bw/
day
oral
doses
on
days
6­
18
of
gestation.
Maternal
toxicity
(
reduced
food
consumption)
was
observed
at
20
mg/
kg
bw/
day,
but
no
developmental
effects
were
observed
at
any
dose.
Therefore,
the
maternal
NOEL
was
4
mg/
kg
bw/
day
and
the
developmental
NOEL
was
greater
than
20
mg/
kg
bw/
day.
4.
Subchronic
toxicity.
i.
Rats
4­
Week:
Male
and
female
rats
were
fed
diets
containing
lactofen
technical
at
concentrations
of
0,
200,
1,000,
5,000,
and
10,000
ppm
for
four
weeks.
A
slight
increase
in
spleen
weight
was
the
basis
for
a
LOEL
of
200
ppm
(
lowest
dose
tested).
At
doses
of
1,000
ppm
or
higher,
the
following
findings
were
reported:
clinical
signs
of
toxicity;
decreased
RBC,
hemoglobin,
hematocrit,
and
increased
WBC;
increased
relative
liver
and
spleen
weights;
and
necrosis
and
pigmentation
of
hepatocytes.
At
10,000
ppm,
severe
toxic
signs
were
observed
by
day
7
and
all
animals
were
dead
or
killed
in
extremis
by
day
11.
Hypocellularity
of
the
spleen,
thymus
and
bone
marrow
was
also
observed
in
animals
exposed
to
10,000
ppm.
ii.
Rats
3­
Month:
lactofen
technical
was
fed
to
male
and
female
rats
at
dietary
concentrations
of
0,
40,
200,
and
1,000
ppm
for
13
weeks.
Histopathological
changes
in
the
liver
and
significant
changes
in
clinical
chemistry
associated
with
the
liver
were
observed
in
rats
exposed
to
1,000
ppm
dosage.
Decreased
RBC,
hemoglobin
and
hematocrit
values
were
also
observed
at
1,000
ppm.
The
NOEL
in
this
study
was
200
ppm
(
14.1
mg/
kg/
day).
iii.
Dogs
4­
week:
In
a
range
finding
study,
lactofen
technical
was
fed
in
the
diet
of
dogs
at
0,
1,000,
3,000,
and
10,000
ppm
for
four
weeks.
Toxic
effects
noted
in
dogs
fed
10,000
ppm
included
decreased
RBC
count
and
hemocrit
and
increased
BUN
and
SGPT.
Food
palatability
problems
led
to
greatly
decreased
feed
consumption
at
higher
dosages.
The
NOEL
was
1,000
ppm
(
0.79
mg/
kg/
day).
iv.
Mice
3­
Month:
Groups
of
male
and
female
mice
were
fed
diets
containing
lactofen
technical
at
concentrations
of
0,
40,
200,
1,000,
5,000,
and
10,000
for
13
weeks.
At
week
five,
the
dosage
of
the
40
ppm
groups
was
increased
to
2,000
ppm.
Treatment
related
mortality
occurred
at
dosages
above
1,000
ppm.
The
LOEL
was
200
ppm
(
28.6
mg/
kg/
day)
based
on:
increased
WBC;
decreased
hematocrit,
hemoglobin
and
RBC;
increased
alkaline
phosphatase,
SGOT,
SGPT,
cholesterol
and
total
serum
protein
levels;
increased
weights
or
enlargement
of
the
spleen,
liver,
adrenals,
heart
and
kidney;
histopathological
changes
of
the
liver,
kidney,
thymus,
spleen,
ovaries
and
testes.
In
general,
effects
were
slight
in
the
200
ppm
groups,
and
moderate
to
severe
in
the
1,000
ppm
groups.
5.
Chronic
toxicity.
Lactofen
causes
adverse
health
effects
when
administered
to
animals
for
extended
periods
of
time.
These
effects
include
proliferative
changes
in
the
liver,
spleen,
and
kidney;
hematological
changes;
and
blood
biochemistry
changes.
i.
Mouse
18­
Month:
In
a
dietary
18­
month
oncogenicity
study
in
mice
at
dosages
of
10,
50
and
250
ppm
lactofen
technical,
an
increase
in
liver
adenomas
and
carcinomas,
cataracts
and
liver
pigmentation
was
observed
at
250
ppm,
a
dose
that
clearly
exceeded
the
MTD.
The
lowest
dose,
10
ppm
(
1.4
mg/
kg/
day),
was
the
LOEL
based
on
increased
liver
weight
and
hepatocytomegaly.
ii.
Rat
24­
Month:
In
a
2­
year
chronic
feeding/
oncogenicity
study
of
lactofen
technical
in
rats
at
dosages
of
0,
500,
1,000
and
2,000
ppm
in
the
diet,
an
increase
in
liver
neoplastic
nodules
and
foci
of
cellular
alteration
was
observed
in
both
sexes
at
2,000
ppm.
The
NOEL
for
systemic
toxicity
is
500
ppm
(
2
mg/
kg/
day)
based
on
kidney
and
liver
pigmentation.
iii.
Dog
12­
Month:
In
a
1­
year
study
in
dogs
exposed
to
40,
200,
and
1,000
(
week
1­
17)
or
3,000
ppm
(
week
18­
52)
lactofen
technical
in
their
diet,
the
NOEL
was
determined
to
be
200
ppm
(
0.79
mg/
kg/
day)
based
on
renal
dysfunction
and
decreased
RBC,
hemoglobin
hematocrit
and
cholesterol
observed
at
1,000/
3,000
ppm.
iv.
Carcinogenicity:
EPA's
Cancer
Assessment
Review
Committee
(
CARC)
has
recently
revised
the
cancer
classification
of
lactofen
based
on
several
mechanistic
studies
showing
that
lactofen
oncogenicity
occurs
via
a
peroxisome
proliferation
mechanism
[
Tolerance
Reassessment
and
Risk
Management
Decision
(
TRED)
for
Lactofen;
Federal
Register
of
January
28,
2004
(
69
FR
4129)
(
OPP­
2003­
0294;
FRL­
7336­
9)].
Lactofen
is
now
classified
under
EPA's
1999
Cancer
Risk
Assessment
Guidelines
as
"
likely
to
be
carcinogenic
to
humans
at
high
enough
doses
to
cause
these
biochemical
and
histopathological
effects
(
peroxisome
proliferation)
in
the
livers
of
rodents
but
unlikely
to
be
carcinogenic
at
doses
below
those
causing
these
changes".
Lactofen
is
a
threshold
carcinogen
with
the
Margin
of
Exposure
(
MOE)
calculated
using
the
NOAEL
of
2
ppm
(
0.3
mg/
kg/
day)
from
a
special
7­
week
rodent
study
which
evaluated
peroxisome
proliferation
in
the
livers
of
rats
and
mice.
In
this
study,
mice
were
exposed
to
lactofen
at
0,
2,
10,
50,
or
250
ppm.
After
7
weeks
of
treatment,
the
mice
were
sacrificed
and
the
livers
examined
biochemically
and
pathologically.
Dose­
dependent
increases
were
observed
in
relative
liver
weights,
in
two
liver
peroxisomal
enzymes,
catalase
and
acyl
CoA
oxidase,
and
in
carnitine
acetyltransferase.
Histological
evaluations
also
revealed
dose­
dependent
increases
in
nuclear
enlargement,
cytoplasmic
eosinophilia,
hypertrophy
and
peroxisomal
staining
in
livers.
These
results
not
only
show
dose­
dependent
increases
in
the
parameters
measured,
but
more
importantly,
a
non­
linear
doseresponse
curve
with
a
NOAEL.
The
NOAEL
of
2
ppm
(
0.3
mg/
kg/
day)
was
based
on
increase
in
relative
liver
weight,
carnitine
acetyl
transferase,
and
palmitoyl
CoA
oxidate
at
a
LOAEL
of
10
ppm
(
1.5
mg/
kg/
day).
Similar
effects
were
seen
in
rats,
exposed
to
lactofen
at
2000
ppm
for
8
weeks.
No
endpoints
were
selected
since
the
rats
were
exposed
at
only
one
high
dose
level.
6.
Animal
metabolism.
In
a
rat
metabolism
study,
lactofen
was
shown
to
metabolize
to
acifluorfen,
5­[
2­
chloro­
4­(
trifluoromethyl)
phenoxy]­
2­
nitrobenzoate,
which
was
eliminated
via
both
urine
and
feces.
While
lactofen
was
the
primary
compound
found
in
the
feces,
acifluorfen
accounted
for
>
90%
of
the
radioactivity
in
the
urine.
Negligible
amounts
of
the
administered
radioactivity
were
found
in
any
tissue
with
less
than
0.8%
of
the
administered
radioactivity
being
found
in
the
liver
(
one
of
the
main
target
organs).
7.
Metabolite
toxicology.
Acifluorfen
is
also
a
hydrolytic
metabolite
of
lactofen.
The
sodium
salt
of
this
benzoic
acid
is
the
registered
herbicide,
sodium
acifluorfen.
The
chronic
population
adjusted
dose
(
c­
PAD)
for
acifluorfen
is
0.004
mg/
kg/
day
for
infants,
children
and
females
13­
50
years
old
and
0.013
mg/
kg/
day
for
other
population
subgroups.
EPA's
Cancer
Assessment
Review
Committee
(
CARC)
has
recently
revised
the
cancer
classification
of
acifluorfen
based
on
mechanistic
studies
showing
that
acifluorfen
oncogenicity
occurs
via
a
peroxisome
proliferation
mechanism
[
Reregistration
Eligibility
Decision
(
RED)
for
the
pesticide
active
ingredient
sodium
acifluorfen;
Federal
Register
of
January
28,
2004
(
69
FR
4136)
(
OPP­
2003­
0293;
FRL­
7337­
1)].
Acifluorfen
is
now
classified
under
EPA's
1999
Cancer
Risk
Assessment
Guidelines
as
"
likely
to
be
carcinogenic
to
humans
at
high
enough
doses
to
cause
these
biochemical
and
histopathological
effects
(
peroxisome
proliferation)
in
the
livers
of
rodents
but
unlikely
to
be
carcinogenic
at
doses
below
those
causing
these
changes".
The
CARC
further
recommended
using
a
MOE
approach
for
estimating
human
cancer
risk
from
exposure
to
acifluorfen.
A
NOAEL
of
25
ppm
(
1.25
mg/
kg/
day)
was
recommended
for
calculating
the
MOE.
Because
lactofen
and
its
metabolites
are
not
retained
in
the
body,
the
potential
for
acute
toxicity
from
in
situ
formed
metabolites
is
low.
The
potential
for
chronic
toxicity
of
lactofen
metabolites
has
been
adequately
addressed
by
an
extensive
battery
of
lactofen
chronic
toxicity
testing.
8.
Endocrine
Disruption:
No
special
studies
to
investigate
the
potential
for
estrogenic
or
other
endocrine
effects
of
lactofen
have
been
performed.
However,
a
large
and
detailed
toxicology
database
exists
for
the
compound
including
studies
acceptable
to
the
Agency
in
all
required
categories.
These
studies
include
evaluations
of
reproduction
and
reproductive
toxicity
and
detailed
pathology
and
histology
of
endocrine
organs
following
repeated
or
longterm
exposure.
These
studies
are
considered
capable
of
revealing
endocrine
effects
and
no
such
effects
were
observed.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Acute
and
chronic
dietary
analyses
were
conducted
to
estimate
exposure
to
potential
lactofen
residues
in/
on
the
following
crops:
soybeans
and
snap
beans
(
existing
tolerances);
cotton
and
peanuts
(
tolerances
pending);
and
fruiting
vegetables
(
tolerances
proposed
in
the
current
petition).
The
Cumulative
and
Aggregate
Risk
Evaluation
System
(
CARES)
Version
2.0
was
used
to
conduct
this
assessment.
This
analysis
utilized
tolerance
level
residues,
consumption
data
from
USDA's
Continuing
Survey
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996,
1998
(
USDA,
2000),
and
the
latest
USEPA
guidance
(
USEPA,
1999
and
USEPA,
2000).
The
reported
dietary
exposure
values
are
based
on
100%
crop
treated.
i.
Food.
a.
Acute­
No
endpoint
has
been
established
to
assess
the
acute
risk
of
exposure
to
lactofen
for
the
general
U.
S.
population.
An
acute
Population
Adjusted
Dose
(
a­
PAD)
has,
however,
been
established
for
females
of
child­
bearing
age
(
13­
50
years
old).
This
a­
PAD
was
calculated
to
be
0.17
mg/
kg/
day
using
the
NOEL
from
the
rat
developmental
study,
50
mg/
kg/
day,
an
uncertainty
factor
of
100
to
account
for
inter­
species
extrapolation
(
10x)
and
intra­
species
variation
(
10x)
and
an
additional
FQPA
safety
factor
of
3.
The
potential
acute
exposure
from
food
to
females
13­
50
years
old
was
calculated
to
be
0.07%
of
the
a­
PAD.
b.
Chronic­
The
NOEL
from
the
chronic
oral
toxicity
study
in
dogs,
0.79
mg/
kg/
day,
was
selected
as
the
chronic
oral
toxicity
endpoint.
Based
on
this
NOEL
and
an
uncertainty
factor
of
100,
the
Chronic
Population
Adjusted
Dose
(
c­
PAD)
for
lactofen
has
been
set
at
0.008
mg/
kg/
day.
The
chronic
dietary
exposure
estimate
of
lactofen
residues
in
food
at
the
100th
percentile
was
calculated
to
be,
at
most,
0.68%
of
the
c­
PAD
with
a
MOE
of
14,469.
The
population
subgroup
with
the
highest
exposure
was
children
1­
2
years
old.
c.
Cancer­
Cancer
margins
of
exposure,
calculated
using
the
0.3
mg/
kg/
day
endpoint
from
the
7­
week
rodent
study
which
evaluated
peroxisome
proliferation
in
the
liver
of
rats
and
mice,
exceed
5,400
for
all
population
subgroups.
The
0.3
mg/
kg/
day
endpoint
is
considered
to
be
protective
of
cancer
effects
because
the
changes
in
liver
enzymes
and
histopathology
are
believed
to
precede
liver
tumor
formation
for
a
peroxisome
proliferation
mode
of
action.
The
Agency,
therefore,
has
no
concern
for
cancer
risks
associated
with
exposure
to
lactofen
in
food.
ii.
Drinking
water.
Lactofen
has
a
low
probability
to
contaminate
drinking
water
because
it
has
a
short
half­
life
(
three
days
or
less)
and
high
binding
potential
(
K
oc
>
1000).
The
HED
Metabolism
Assessment
Review
Committee
(
MARC)
has
concluded
that
the
residues
of
concern
in
drinking
water
are
the
degradates
acifluorfen
and
amino
acifluorfen.
Insufficient
information
is
available
to
estimate
the
amino
acifluorfen
concentration
in
water,
but
it
is
likely
to
be
less
than
that
of
acifluorfen.
Laboratory
studies
have
shown
that
acifluorfen
reaches
its
maximum
concentration
of
53.3%
of
applied
lactofen
at
7
days
following
application
and
it
is
most
likely
to
form
under
the
soil
surface.
Thus,
the
formed
acifluorfen
is
not
subject
to
drift,
erosion,
or
runoff
forces
that
contribute
to
surface
water
contamination.
Surface
water,
however,
could
be
contaminated
with
acifluorfen
from
lactofen
applications
via
spray
drift.
The
registrant
also
has
conducted
two
prospective
groundwater
studies
which
showed
that
neither
lactofen
nor
acifluorfen
(
from
lactofen
applications)
contaminate
groundwater.

To
assess
the
acute,
chronic,
and
cancer
risks
associated
with
exposure
to
lactofen
and
acifluorfen
(
from
applications
of
lactofen)
in
surface
water,
OPP
has
calculated
drinking
water
levels
of
comparison
(
DWLOCs)
and
Estimated
Drinking
Water
Concentrations
(
EDWCs)
[
Tolerance
Reassessment
of
Risk
Management
Decision
(
TRED)
for
Lactofen;
Federal
Register
of
January
28,
2004
(
69
FR
4129)
(
OPP­
2003­
0294;
FRL­
7336­
9)].
EDWCs
that
are
above
the
corresponding
DWLOC
exceed
the
Agency's
level
of
concern.

Dietary
Exposure
and
Risk
to
Lactofen
from
Drinking
Water
Exposure
EDWC
(
ppb)
DWLOC
(
ppb)
Surface
Water
Groundwater
Acute
0.39
0.006
5100
Chronic
(
non­
cancer)
0.008
0.006
80
Cancer
0.007
0.006
105
Dietary
Exposure
and
Risk
to
Acifluorfen
from
Drinking
Water
Exposure
EDWC
(
ppb)
DWLOC
(
ppb)
Surface
Water
Groundwater
Acute
10
3.7
600
Chronic
(
non­
cancer)
2.4
3.7
40
Cancer
1.3
3.7
455
The
EDWC
values
for
all
exposures
are
less
than
the
corresponding
DWLOC
values;
therefore,
the
Agency
has
no
concern
for
the
aggregate
risk
of
lactofen
and
acifluorfen
from
lactofen
in
drinking
water.
2.
Non­
dietary
exposure.
Lactofen
is
proposed
only
for
agricultural
uses
and
no
homeowner
or
turf
uses.
Thus,
no
non­
dietary
risk
assessment
is
needed.

D.
Cumulative
Effects
Section
408(
b)(
2)(
D)(
v)
requires
that
the
Agency
must
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
Available
information
in
this
context
include
not
only
toxicity,
chemistry,
and
exposure
data,
but
also
scientific
policies
and
methodologies
for
understanding
common
mechanisms
of
toxicity
and
conducting
cumulative
risk
assessments.
For
most
pesticides,
although
the
Agency
has
some
information
in
its
files
that
may
turn
out
to
be
helpful
in
eventually
determining
whether
a
pesticide
shares
a
common
mechanism
of
toxicity
with
any
other
substances,
EPA
does
not
at
this
time
have
the
methodologies
to
resolve
the
complex
scientific
issues
concerning
common
mechanism
of
toxicity
in
a
meaningful
way.
There
are
other
pesticidal
compounds
that
are
structurally
related
to
lactofen
and
have
similar
effects
on
animals.
In
consideration
of
potential
cumulative
effects
of
lactofen
and
other
substances
that
may
have
a
common
mechanism
of
toxicity,
there
are
currently
no
available
data
or
other
reliable
information
indicating
that
any
toxic
effects
produced
by
lactofen
would
be
cumulative
with
those
of
other
chemical
compounds.
Thus,
only
the
potential
risks
of
lactofen
have
been
considered
in
this
assessment
of
aggregate
exposure
and
effects.
Valent
will
submit
information
for
EPA
to
consider
concerning
potential
cumulative
effects
of
lactofen
consistent
with
the
schedule
established
by
EPA
at
62
Federal
Register
42020
(
Aug.
4,
1997)
and
other
subsequent
EPA
publications
pursuant
to
the
Food
Quality
Protection
Act.

E.
Safety
Determination
Water
is
not
expected
to
be
a
significant
source
of
exposure
for
lactofen,
as
it
degrades
quickly
in
the
environment
to
numerous
degradates,
including
acifluorfen.
Estimated
drinking
water
concentrations
(
EDWCs)
for
lactofen
and
acifluorfen
are
well
below
the
Drinking
Water
Levels
of
Comparison
(
DWLOCs)
for
chronic,
acute,
and
cancer
risk.
Therefore,
the
only
significant
source
of
human
exposure
to
lactofen
is
in
food.
1.
U.
S.
population.
i.
Acute
Risk.
No
endpoint
has
been
established
to
assess
the
acute
risk
of
exposure
to
lactofen
for
the
general
U.
S.
population.
An
a­
PAD
has,
however,
been
established
for
females
of
child­
bearing
age
(
13­
50
years
old)
and
it
has
been
estimated
that
the
potential
acute
exposure
from
food
to
this
population
subgroup
will
the
utilize
0.07%
of
the
a­
PAD.
The
Agency
has
no
cause
for
concern
if
total
acute
residue
contribution
is
less
than
100%
of
the
a­
PAD.
Therefore,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
this
subpopulation
from
aggregate,
acute
exposure
to
lactofen
residues.
ii.
Chronic
Risk.
The
potential
chronic
exposure
from
food
to
the
U.
S.
Population
and
various
non­
child/
infant
population
subgroups
will
utilize
at
most
0.66%
of
the
c­
PAD.
The
Agency
has
no
cause
for
concern
if
total
chronic
residue
contribution
is
less
than
100%
of
the
c­
PAD.
Therefore,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
overall
U.
S.
Population
from
aggregate,
chronic
exposure
to
lactofen
residues.
iii.
Cancer
Risk.
Cancer
margins
of
exposure,
calculated
using
the
0.3
mg/
kg/
day
endpoint
from
the
7­
week
rodent
study
which
evaluated
peroxisome
proliferation
in
the
liver
of
rats
and
mice,
exceed
5,600
for
all
non­
child/
infant
population
subgroups.
The
Agency,
therefore,
has
no
concern
for
cancer
risks
associated
with
exposure
of
the
general
population
to
lactofen
in
food.
2.
Infants
and
children.
i.
Safety
Factor
for
Infants
and
Children.
Reproduction
and
developmental
effects
have
been
found
in
toxicology
studies
for
lactofen
but
only
at
levels
that
were
also
maternally
toxic.
This
indicates
that
developing
animals
are
not
more
sensitive
than
adults.
ii.
Chronic
Risk.
The
potential
chronic
exposure
from
food
to
children
1­
2
years
old
(
the
most
highly
exposed
child/
infant
subgroup)
will
utilize
0.68%
of
the
c­
PAD.
Therefore,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate,
chronic
exposure
to
flumioxazin
residues.
iii.
Cancer
Risk.
Cancer
margins
of
exposure,
calculated
using
the
0.3
mg/
kg/
day
endpoint
from
the
7­
week
rodent
study
which
evaluated
peroxisome
proliferation
in
the
liver
of
rats
and
mice,
exceed
5,400
for
all
child/
infant
population
subgroups.
The
Agency,
therefore,
has
no
concern
for
cancer
risks
associated
with
exposure
of
infants
and
children
to
lactofen
in
food.

F.
International
Tolerances.
There
are
no
Codex
Maximum
Residue
Limits
(
MRLs)
established
for
lactofen
on
fruiting
vegetable
commodities,
so
there
is
no
conflict
between
this
proposed
action
and
international
residue
limits.
