Document ID: EPA-HQ-OPP-2006-0103-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-15T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
28­
JAN­
2005
SUBJECT:
ID#
04TX20.
Section
18
Specific
Exemption
for
the
Use
of
Triflumizole
on
Parsley,
Dandelion,
Swiss
chard,
Collards,
Kale,
Kohlrabi,
Mustard
Greens,
Napa
cabbage,
Broccoli
and
Cilantro
in
Texas.
DP#:
306463.
Chemical
#:
128879.
Trade
Name:
Procure
®
50WS.
40
CFR
§
180.476.
EPA
Reg#:
400­
431.

FROM:
Jennifer
R.
Tyler,
Chemist
Mark
I.
Dow,
Ph.
D.,
Biologist
Robert
Mitkus,
Toxicologist
Registration
Action
Branch
1
(
RAB
1)
Health
Effects
Division
(
HED)
(
7509C)

THRU
PV
Shah,
Branch
Senior
Scientist
HED/
RAB1
(
7509C)

TO:
Libby
Pemberton/
Robert
Forrest,
PM
Team
05
Registration
Division
(
RD)
(
7505C)

INTRODUCTION
In
accordance
with
40
CFR
166.20,
the
Texas
Department
of
Agriculture
(
TDA)
proposes
a
Section
18
Specific
Emergency
Exemption
for
the
use
of
triflumizole
on
parsley,
dandelion,
Swiss
chard,
collards,
kale,
kohlrabi,
mustard
greens,
Napa
cabbage,
broccoli
and
cilantro
to
control
Powdery
Mildew.
This
is
the
first
year
TDA
has
requested
this
Emergency
Exemption.
The
proposed
program
will
entail
the
application
of
63,000
oz.
of
Procure
50WS
[
1,969
pounds
active
ingredient
(
a.
i.)]
on
a
total
of
5,250
acres
of
turnip
greens
(
200
acres),
broccoli
(
1000
acres),
mustard
greens
(
1800
acres),
parsley
(
600
acres),
dandelion
(
150
acres),
Swiss
chard
(
250
acres),
kohlrabi
(
300
acres),
Napa
cabbage
(
150
acres),
kale
(
500
acres),
and
cilantro
(
300
acres)
starting
October
1,
2003.

NOTE:
HED
recently
completed
a
Section
3
risk
assessment
for
the
use
of
triflumizole
on
strawberries,
cucurbit
vegetables,
cherries
and
hazelnuts
(
Memo,
J.
Tyler,
et
al.
4/
25/
02;
D280864).
This
document
contains
only
those
aspects
of
the
risk
assessment
which
are
affected
by
the
addition
of
this
new
use
of
triflumizole
on
parsley,
dandelion,
Swiss
chard,
collards,
kale,
2
kohlrabi,
mustard
greens,
Napa
cabbage,
broccoli
and
cilantro.
Dietary,
occupational
and
aggregate
risk
were
re­
evaluated
based
on
the
addition
of
the
aforementioned
crops
to
the
triflumizole
use
pattern.

SUMMARY
Triflumizole
is
an
imidazole
fungicide
that
inhibits
ergosterol
biosynthesis
in
fungi.
Ergosterol
is
a
sterol
which
is
thought
to
function
as
a
stabilizer
for
the
membranes
that
make
up
the
cell
wall
of
fungi.
Triflumizole
is
currently
registered
for
use
on
apples,
cherries,
grapes,
pears,
strawberries,
cucurbit
vegetables
and
filberts
as
well
as
ornamentals
in
greenhouses,
shadehouses,
nurseries
(
including
Christmas
tree/
conifer
plantations),
and
interiorscapes.
There
are
currently
no
registered
or
proposed
homeowner
applicator
uses.
The
proposed
residential
applications
of
triflumizole
will
be
made
by
commercial
applicators
only.

RECOMMENDATIONS
Provided
the
label
is
amended
as
specified
on
page
10,
the
toxicology,
chemistry
and
occupational/
residential
exposure
databases
are
adequate
to
support
a
time­
limited
tolerance
of
7.0
ppm
for
the
combined
residues
of
triflumizole
and
its
metabolites
containing
the
4­
chloro­
2­
trifluoromethylaniline
moiety,
calculated
as
the
parent
compound,
in/
on
the
following
RACs:
parsley,
leaves
at
9.0
ppm;
dandelion,
leaves
at
7.0
ppm;
Swiss
chard
at
7.0
ppm;
collards
at
9.0
ppm;
kale
at
9.0
ppm;
kohlrabi
at
9.0
ppm;
mustard
greens
at
9.0
ppm;
Napa
cabbage
at
9.0
ppm;
broccoli
at
1.0
ppm;
and
cilantro
at
9.0
ppm.

HAZARD
CHARACTERIZATION
In
HED's
most
recent
human
health
risk
assessment,
the
following
toxicity
studies
were
determined
to
be
data
gaps:
a
28­
day
rat
inhalation
study
(
GLN
870.3465),
acute
rat
neurotoxicity
study
(
GLN
870.6200),
and
subchronic
rat
neurotoxicity
study
(
GLN
870.6200).
The
acute
and
sub­
chronic
neurotoxicity
studies
have
been
submitted,
reviewed
by
HED
and
determined
to
be
acceptable
(
R.
Fricke,
TXR#
0052656).
As
a
result
the
following
has
changed:
1)
selection
of
an
acute
endpoint
for
the
general
U.
S.
population
(
including
infants
and
children);
and
2)
the
removal
of
the
3x
database
uncertainty
factor
(
UF
DB
).
All
other
aspects
of
the
most
recent
risk
assessment
remain
unchanged.
Updated
toxicity
profile
and
dose
and
endpoint
selection
tables
can
be
found
as
Attachment
1.

Food
Quality
Protection
Act
(
FQPA)
Considerations
The
2/
17/
02
HED
hazard
identification
assessment
review
committee
(
HIARC)
meeting
for
triflumizole
took
place
before
the
current
10x
FQPA
Policy
[
Determination
of
the
Appropriate
FQPA
Safety
Factor(
s)
in
Tolerance
Assessment;
2/
28/
02]
had
been
implemented
by
HED
in
assessing
the
risks
to
infants
and
children.
On
3/
4/
02,
the
FQPA
Safety
Factor
Committee
(
SFC)
reviewed
the
recommendations
of
the
presenting
chemical
team
from
RAB1
to
apply
a
3x
UF
DB
to
the
acute
and
chronic
reference
doses
(
RfDs)
for
an
incomplete
database.
The
HIARC
recommended
that
an
acute
neurotoxicity
study
and
a
subchronic
neurotoxicity
study
be
submitted
in
order
to
better
characterize
the
neurological
effects
seen
in
the
rat
and
mouse
acute
oral,
the
rat
acute
inhalation
and
the
rat
chronic
studies.
The
FQPA
SFC
recommended
a
UFDB
3
of
3x
be
applied
to
the
acute
and
chronic
RfDs
in
order
to
account
for
any
uncertainty
due
to
the
lack
of
these
two
neurotoxicity
studies
(
Memo,
D.
Nixon,
3/
17/
02;
TXR
NO.
0050571).
Acceptable
acute
and
subchronic
rat
neurotoxicity
and
subchronic
rat
neurotoxicity
study
(
GLN
870.6200).
As
acceptable
acute
and
sub­
chronic
neurotoxicity
studies
have
been
submitted,
the
risk
assessment
team
has
determined
that
the
3x
UF
DB
should
be
removed
from
the
acute
and
chronic
RfDs.
In
addition,
the
FQPA
SFC
recommended
a
special
FQPA
SF
be
reduced
to
1x.
The
risk
assessment
team
has
re­
evaluated
the
quality
of
the
exposure
and
hazard
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
remain
at
1x.
The
recommendation
is
based
on
the
following:

°
The
toxicity
database
is
complete
for
FQPA
assessment.
°
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
rabbit
fetuses
following
in
utero
exposure
or
the
rat
following
pre­
and
post­
natal
exposure
in
the
rat
reproduction
study.
°
There
was
evidence
of
qualitative
susceptibility
in
the
developmental
rat
study,
however,
there
are
no
residual
uncertainties,
and
the
use
of
the
developmental
No­
Observed­
Adverse­
Effect­
Level
(
NOAEL)
and
the
endpoint
for
the
acute
RfD
for
females
13­
50
would
be
protective
of
the
pre­
natal
toxicity
following
an
acute
dietary
exposure.
°
There
is
no
evidence
of
increased
quantitative
or
qualitative
susceptibility
in
the
rat
developmental
neurotoxicity
study.
°
The
acute
dietary
food
exposure
assessment
utilizes
existing
and
proposed
tolerance
level
residues
and
100%
CT
information
for
all
commodities.
By
using
these
screening­
level
assessments,
actual
exposures/
risks
will
not
be
underestimated.
°
The
chronic
dietary
food
exposure
assessment
utilizes
anticipate
residues
(
ARs)
and
percent
crop
treated
(%
CT)
data
verified
by
Biological
and
Economics
Analysis
Division
(
BEAD)
for
several
existing
uses.
For
all
proposed
use,
tolerance­
level
residue
and
100%
CT
is
assumed.
The
chronic
assessment
is
somewhat
refined
and
based
on
reliable
data
and
will
not
underestimate
exposure/
risk.
°
The
dietary
drinking
water
assessment
utilizes
water
concentration
values
generated
by
model
and
associated
modeling
parameters
which
are
designed
to
provide
conservative,
health
protective,
high­
end
estimates
of
water
concentrations
which
will
not
likely
be
exceeded.
°
There
are
no
registered
or
proposed
uses
of
triflumizole
that
would
result
in
residential
exposure.

Dose­
Response
Assessment
Acute
Dietary
Endpoint
(
General
U.
S.
Population):
The
rat
acute
neurotoxicity
study
was
chosen
to
select
the
endpoint
for
establishing
the
acute
RfD
of
0.25
mg/
kg
for
the
general
U.
S.
population,
including
infants
and
children.
The
NOAEL
of
25
mg/
kg/
day
was
based
on
FOB
findings
(
neuromuscular
impairment)
and
decreased
locomotor
activity
observed
at
the
LOAEL
of
100
mg/
kg/
day.
A
100­
fold
UF
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation)
was
incorporated
in
the
acute
RfD.
The
risk
assessment
team
has
evaluated
the
quality
of
the
exposure
and
hazard
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
remain
at
1x.
Thus,
the
acute
population
adjusted
dose
(
aPAD)
is
0.25
mg/
kg/
day
for
the
general
U.
S
population,
including
infants
and
children.

Acute
Dietary
Endpoint
(
Females
13­
49
Years
Old):
The
rat
developmental
studies
were
chosen
to
select
the
endpoint
for
establishing
the
acute
RfD
of
0.1
mg/
kg
for
the
subpopulation
females
13­
50
years
old.
The
developmental
NOAEL
of
10
mg/
kg/
day
was
based
on
decreased
numbers
of
viable
fetuses,
increased
dead
or
resorbed
fetuses,
increased
numbers
of
late
resorptions,
decreased
fetal
body
weight,
and
increased
incidences
of
cervical
ribs
observed
at
the
LOAEL
of
35
mg/
kg/
day.
A
100­
fold
UF
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation)
was
incorporated
in
the
acute
RfD.
The
FQPA
SFC
determined
that
a
special
FQPA
safety
factor
of
1x
is
applicable
for
acute
dietary
risk
assessment
(
females
13­
49
years
old).
The
risk
assessment
team
has
re­
evaluated
the
quality
of
the
exposure
and
hazard
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
remain
at
1x.
Thus,
the
aPAD
is
0.1
mg/
kg/
day.

Chronic
Dietary
Endpoint:
The
rat
reproduction
study
was
used
to
select
the
endpoint
for
establishing
the
chronic
RfD
of
0.015
mg/
kg/
day.
The
NOAEL
of
1.5
mg/
kg/
day
was
based
on
4
increased
gestation
length
in
the
dams
of
the
F
3a
interval
at
the
LOAEL
of
3.5
mg/
kg/
day.
A
100­
fold
UF
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation)
was
incorporated
into
the
chronic
RfD.
The
FQPA
SFC
determined
that
a
special
FQPA
safety
factor
of
1x
is
applicable
for
chronic
dietary
risk
assessment.
The
risk
assessment
team
has
reevaluated
the
quality
of
the
exposure
and
hazard
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
remain
at
1x.
Thus,
the
chronic
population
adjusted
dose
(
cPAD)
is
0.015
mg/
kg/
day.

EXPOSURES
AND
RISKS
In
examining
aggregate
exposure,
FQPA
directs
EPA
to
consider
available
information
concerning
exposures
from
pesticide
residues
in
food
and
all
other
non­
dietary,
non­
occupational
exposures
(
i.
e.,
residential).
The
primary
non­
food
sources
of
non­
occupational
exposure
is
drinking
water
(
from
both
groundwater
and
surface
water).
There
are
no
uses
that
would
result
in
residential
exposure
to
children.
In
evaluating
food
exposures,
EPA
takes
into
account
varying
consumption
patterns
of
major
identifiable
subgroups
of
consumers,
including
infants
and
children.

Dietary
Risks
from
Food
A
triflumizole
acute
[
separate
assessment
for
general
U.
S.
population
(
including
infants
and
children)
and
females
13­
49
years
old]
and
chronic
dietary
exposure
(
general
U.
S.
population
and
all
population
subgroups)
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
­
Food
Commodity
Intake
Database
 
(
DEEM­
FCID
 
;
ver.
2.03)
program
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998
(
Memo,
J.
Tyler,
D312453,
1/
28/
05).
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
nonconsecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.

For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(
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
body
weight/
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
(
Tier
1
or
Tier
2)
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(
Tier
3/
4)
assessment.
The
resulting
5
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.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
Tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.

HED's
level
of
concern
is
when
the
exposure
is
greater
than
100%
of
the
PAD.
That
is,
estimated
exposures
above
this
level
are
of
concern,
while
estimated
exposures
at
or
below
this
level
are
not
of
concern.
The
DEEM­
FCID
 
analysis
estimates
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table
1
are
for
the
U.
S.
Population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
females
13­
49,
males
20­
49,
and
adults
50+
years.

Acute
Dietary
Exposure
Estimates:
Acute
dietary
exposure
assessments
were
conducted
for
the
general
U.
S.
population
(
including
infants
and
children)
and
females
13­
49
years
old
using
tolerance
level
residues
and
100%
CT
information
for
all
registered
and
proposed
uses).
These
assessments
conclude
that
the
acute
dietary
exposure
estimates
are
below
HED's
level
of
concern
(<
100%
aPAD)
for
the
general
U.
S.
population
(
including
infants
and
children;
#
21%
aPAD)
and
females
13­
49
years
old
(
9%
aPAD).

Chronic
Dietary
Exposure
Estimates:
A
refined,
chronic
dietary
exposure
assessment
was
performed
for
the
general
U.
S.
population
and
various
population
subgroups
using
anticipated
residues
(
ARs)
from
average
field
trial
residues
for
apple,
grape,
pear,
cherry,
cucurbit,
strawberry,
and
milk
commodities;
registered
and
proposed
tolerance
for
all
other
commodities;
%
CT
information
for
apples,
grapes
and
pear
commodities;
and
100%
CT
information
for
all
other
uses).
This
assessment
concludes
that
the
chronic
dietary
exposure
estimates
are
below
HED's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
(
5%
cPAD)
and
all
population
subgroups.
The
most
highly
exposed
population
subgroup
is
Children
1­
2
years
old
at
13%
cPAD.

Table
1.
Summary
of
Dietary
Exposure
and
Risk
for
Triflumizole.

Population
Subgroup
Acute
Dietary
1
Chronic
Dietary
2
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
(
total)
0.013798
6
0.000788
5
All
Infants
(<
1
year
old)
0.028361
11
0.000637
4
Children
1­
2
years
old
0.052241
21
0.001967
13
Children
3­
5
years
old
0.035753
14
0.001768
12
Children
6­
12
years
old
0.016749
7
0.001019
7
Youth
13­
19
years
old
0.008281
3
0.000749
5
Table
1.
Summary
of
Dietary
Exposure
and
Risk
for
Triflumizole.

Population
Subgroup
Acute
Dietary
1
Chronic
Dietary
2
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
(
total)
0.013798
6
0.000788
5
6
Adults
20­
49
years
old
0.008492
3
0.000599
4
Adults
50+
years
old
0.009758
4
0.000725
5
Females
13­
49
years
old
0.009380
9
0.000593
4
1.
Acute
dietary
endpoints
of
0.25
mg/
kg/
day
and
0.1
mg/
kg/
day
applies
to
the
general
U.
S.
population
(
including
infants
and
children)
and
females
13­
49
years
old,
respectively.
2.
Chronic
dietary
endpoint
of
0.015
mg/
kg/
day
applies
to
the
general
U.
S.
population
and
all
population
subgroups.

Dietary
Risks
From
Drinking
Water
The
Environmental
Fate
and
Effects
Division
(
EFED)
provided
revised
Tier
1
drinking
water
EECs
to
include
the
degradates
containing
the
4­
chloro­
2­
trifluoromethylaniline
moiety
(
Memo,
S.
Ramasamy,
3/
13/
02).
The
EECs
derived
for
total
residues,
namely
parent
and
degradates
containing
the
4­
chloro­
2­
trifluoromethyl
aniline
moiety,
as
Metabolism
Assessment
Review
Committee
(
MARC)
suggested,
are
based
on
certain
assumptions
in
the
absence
of
some
fate
studies
for
degradates
(
i.
e.,
mobility
studies)
and
may
be
associated
with
uncertainties
in
the
water
assessment.
Tier
I
models
Screening
Concentration
in
Ground
Water
(
SCI­
GROW)
and
FQPA
Index
Reservoir
Screening
Tool
(
FIRST)
were
used
to
derive
the
surface
water
and
ground
water
EECs,
respectively.
Application
to
cherries
provided
the
highest
exposure
scenario
(
0.5
lb
ai/
A/
application
×
6
applications/
year
=
3.0
lb
ai/
A/
year);
therefore,
the
drinking
water
EECs
were
derived
for
cherries.
The
ground
water
EEC
was
0.12
ppb.
The
acute
and
chronic
surface
water
EECs
were
191
and
40
ppb,
respectively.

Aggregate
Risks
Aggregate
risk
assessments
were
performed
for
acute
and
chronic
aggregate
exposure
(
food
+
drinking
water).
Short­,
intermediate­
and
long­
term
aggregate
risk
assessments
were
not
performed
because,
there
are
no
registered
or
proposed
residential
uses
for
triflumizole.
A
cancer
aggregate
risk
assessment
was
not
performed
because
triflumizole
is
not
carcinogenic.
All
potential
exposure
pathways
were
assessed
in
the
aggregate
risk
assessment.

Since
HED
does
not
have
ground
and
surface
water
monitoring
data
to
calculate
a
quantitative
aggregate
exposure,
drinking
water
levels
of
comparison
(
DWLOCs)
were
calculated.
A
DWLOC
is
a
theoretical
upper
limit
on
a
pesticide's
concentration
in
drinking
water
in
light
of
total
aggregate
exposure
to
a
pesticide
through
food,
drinking
water,
and
residential
uses.
A
DWLOC
will
vary
depending
on
the
toxicity
endpoint,
drinking
water
consumption,
body
weights,
and
pesticide
uses.
Different
populations
will
have
different
DWLOCs.
HED
uses
DWLOCs
in
the
risk
assessment
process
to
assess
potential
concern
for
exposure
associated
with
pesticides
in
drinking
water.
DWLOC
values
are
not
regulatory
standards
for
drinking
water.

To
calculate
DWLOCs,
the
dietary
food
estimates
(
from
DEEM­
FCID
 
)
were
subtracted
from
7
the
PAD
value
to
obtain
the
maximum
water
exposure
level.
DWLOCs
were
then
calculated
using
the
standard
body
weights
and
drinking
water
consumption
figures:
70kg/
2L
(
adult
male
and
U.
S.
population),
60
kg/
2L
(
adult
female
and
youth),
and
10kg/
1L
(
infants
and
children).

Acute
Aggregate
Risk
Assessment
(
Food
and
Drinking
Water):
The
acute
aggregate
risk
assessment
considered
exposure
from
food
and
water.
The
acute
dietary
exposure
estimates
are
below
HED's
level
of
concern
(<
100%
aPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(
see
Table
1).
The
EECs
generated
by
EFED
are
less
than
HED's
DWLOCs.
Acute
aggregate
risk
to
triflumizole,
as
a
result
of
all
registered
and
proposed
uses,
is
less
than
HED's
level
of
concern.
Table
2
summarizes
the
acute
aggregate
risk
to
triflumizole.

Table
2.
Acute
Aggregate
Risk
to
Triflumizole
Population
aPAD
(
mg/
kg/
day)
Acute
Food
Exposure
(
mg/
kg/
day)
Max
Acute
Water
Exposure1
(
mg/
kg/
day)
Ground
Water
EEC2
(
ppb)
Surface
Water
EEC2
(
ppb)
Acute
DWLOC3
(
ppb)

General
U.
S.
Population
0.25
0.013798
0.237202
0.12
191
8300
All
Infants
(<
1
year
old)
0.028361
0.221639
2200
Children
1­
2
years
old
0.052241
0.197759
2000
Children
3­
5
years
old
0.035753
0.214247
2100
Children
6­
12
years
old
0.016749
0.237251
2400
Youth
13­
19
years
old
0.008281
0.241719
7300
Adults
20­
49
years
old
0.008492
0.241508
8500
Adults
50+
years
old
0.009758
0.240242
8400
Females
13­
49
years
old
0.1
0.009380
0.090620
0.12
191
2700
1.
maximum
acute
water
exposure
(
mg/
kg/
day)
=
aPAD
(
mg/
kg/
day)
­
acute
food
exposure
from
DEEM
(
mg/
kg/
day);
no
res.
exp.
2.
FIRST
and
SCI­
GROW
modeling
EECs
(
Tier
1);
cherry
application
used
(
3.0
lb
ai/
A/
year)
3.
DWLOC(
µ
g/
L)
=
(
allowable
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)
x
1000
µ
g/
mg)
÷
(
water
consumption
(
liters))

Chronic
Aggregate
Risk
Assessment
(
Food
and
Drinking
Water):
The
chronic
aggregate
risk
assessment
considered
exposure
from
food
and
water.
The
chronic
dietary
exposure
estimates
are
below
HED's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(
see
Table
1).
The
EECs
generated
by
EFED
are
less
than
HED's
DWLOCs.
Chronic
aggregate
risk
to
triflumizole,
as
a
result
of
all
registered
and
proposed
uses,
is
less
than
HED's
level
of
concern.
Table
3
summarizes
the
chronic
aggregate
risk
to
triflumizole.
8
Table
3.
Chronic
Aggregate
Risk
to
Triflumizole
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
0.015
0.000788
0.014212
0.12
40
500
All
Infants
(<
1
year
old)
0.000637
0.014363
140
Children
1­
2
years
old
0.001967
0.013033
130
Children
3­
5
years
old
0.001768
0.013232
130
Children
6­
12
years
old
0.001019
0.013981
140
Youth
13­
19
years
old
0.000749
0.014251
430
Adults
20­
49
years
old
0.000599
0.014401
500
Females
13­
49
years
old
0.000593
0.014407
430
Adults
50+
years
old
0.000725
0.014275
500
1
maximum
chronic
water
exposure
(
mg/
kg/
day)
=
cPAD
(
mg/
kg/
day)
­
chronic
food
exposure
from
DEEM
(
mg/
kg/
day);
no
res.
exp.
2
FIRST
and
SCI­
GROW
modeling
EECs
(
Tier
1);
cherry
application
used
(
3.0
lb
ai/
A)
3
DWLOC(
µ
g/
L)
=
(
allowable
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)
x
1000
µ
g/
mg)
÷
(
water
consumption
(
liters))

Occupational
Exposure
and
Risk
Assessment
See
Attachment
2
for
a
summary
of
the
proposed
use
pattern.
The
label
requires
applicators
and
other
handlers
to
wear
long­
sleeved
shirt,
long
pants,
shoes
plus
socks
and
chemical
resistant
gloves
made
of
any
waterproof
material.

Occupational
Handler
Exposure:
In
this
case,
the
most
highly
exposed
occupational
pesticide
handlers
are
likely
to
be
a
mixer
loader
using
open
pour
of
wettable
powder,
an
applicator
using
open
cab
ground
boom
equipment
and
an
aerial
applicator.
Based
upon
the
proposed
use
pattern,
HED
believes
occupational
pesticide
handlers
(
i.
e.,
mixers,
loaders,
applicators)
will
be
exposed
to
short­
term
(
1
­
30
days)
duration
exposures.
Intermediate­
term
exposures
(
1
­
6
months)
are
not
expected.
Treatment
blocks
are
expected
to
be
small
in
comparison
to
typical
field
crops
such
as
corn,
wheat,
cotton
or
soybeans.
Although
multiple
applications
are
possible,
they
are
separated
by
10
­
14
days.
It
is
expected
that
private
(
i.
e.,
grower)
applicators
will
apply
the
majority
of
acres
treated.

Private
(
i.
e.,
grower)
applicators
may
perform
all
functions,
that
is,
mix,
load
and
apply
the
material.
The
HED
Science
Advisory
Council
for
Exposure
(
ExpoSAC)
Policy
12
(
29
March
2000)
directs
that
although
the
same
individual
may
perform
all
those
tasks,
they
shall
be
assessed
separately.
"
By
separating
the
two
job
functions,
(
i.
e.,
mixing/
loading
from
application)
HED
determines
the
most
appropriate
levels
of
personal
protection
equipment
(
PPE)
for
each
aspect
of
the
job
without
requiring
an
applicator
to
wear
unnecessary
PPE
that
may
be
required
for
mixer/
loaders
(
e.
g.,
chemical
resistant
gloves
may
only
be
necessary
during
the
pouring
of
a
liquid
formulation)."

Chemical
specific
data
were
not
available
with
which
to
assess
pesticide
handler
exposure.
Therefore,
surrogate
data
from
studies
in
the
Pesticide
Handler
Exposure
Database
(
PHED,
Version
1.1,
August
1998)
were
used
to
estimate
mixer/
loader
and
applicator
exposure.

It
is
HED
policy
to
assess
handler
exposure
and
risk
using
"
baseline"
PPE
which
is
comprised
of
long
9
sleeved
shirt,
long
pants,
and
shoes
plus
socks
and
if
necessary
to
assess
"
baseline"
plus
the
use
of
protective
gloves
or
other
PPE
as
might
be
necessary
or
appropriate.
The
Procure
®
50
WS
label
directs
pesticide
handlers
to
wear
a
long
sleeved
shirt,
long
pants,
chemical
resistant,
water
proof
gloves
and
shoes
plus
socks.
See
Table
4
for
a
summary
of
estimated
exposures
and
risks
to
occupational
pesticide
handlers.

Table
4.
Estimated
Handler
Exposure
and
Risk
from
the
Use
of
Triflumizole
on
Broccoli
and
Vegetable
Greens.

Unit
Exposure1
mg
a.
i./
lb
handled
Applic.
Rate2
(
lb
ai/
A)
Units
Treated3
Per
Day
(
Acres)
Average
Daily
Dose4
(
mg
a.
i./
kg
bw/
day)
NOAEL5
(
mg
a.
i./
kg
bw/
day)
MOE6
Mixer/
Loader
­
Wettable
Powder
­
Open­
pour
Dermal:
No
Glove
3.7
LC
With
Glove
0.17
MC
Inhal.
0.043
MC
0.1875
lb
a.
i./
A
350A
Dermal:
No
Glove
0.014
W
Glove
0.0065
Inhal
0.047
8.5
No
Glove
140
W
Glove
160
Applicator
­
Ground­
boom
­
Open
Cab
Dermal:
No
Glove
0.014
HC
With
Glove
0.014
MC
Inhal
0.00074
HC
0.1875
lb
a.
i./
A
200
A
Dermal:
No
Glove
0.00031
W
Glove
0.00031
Inhal
0.00046
8.5
No
Glove
11,000
W
Glove
11,000
Aerial
Applicator
(
pilots
not
required
to
wear
gloves)

Dermal:
No
Glove
0.0022
MC
Inhal.
0.000068
MC
0.1875
lb
a.
i./
A
350A
Dermal:
No
Glove
0.000084
Inhal
0.000074
8.5
No
Glove
53,000
1.
Unit
Exposures
are
taken
from
"
PHED
SURROGATE
EXPOSURE
GUIDE",
Estimates
of
Worker
Exposure
from
The
Pesticide
Handler
Exposure
Database
Version
1.1,
August
1998.
Dermal
=
Single
Layer
Work
Clothing
No
Gloves;
Single
Layer
Work
Clothing
With
Gloves;
Inhal.
=
Inhalation.
Units
=
mg
a.
i./
pound
of
active
ingredient
handled.
Data
Confidence:
LC
=
Low
Confidence,
MC
=
Medium
Confidence,
HC
=
High
Confidence.
2.
Applic.
Rate.
=
Taken
from
the
Texas
Section
18
request.
3.
Units
Treated
are
taken
from
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture";
SOP
No.
9.1.
Science
Advisory
Council
for
Exposure;
Revised
5
July
2000;
4.
Average
Daily
Dose
=
Unit
Exposure
*
Applic.
Rate
*
Units
Treated
*
absorption
factor
(
3.5
%
dermal;
100
%
inhalation
÷
Body
Weight
(
60
kg
since
NOAELs
are
identified
from
a
developmental
study
with
fetal
effects).
5.
NOAEL
=
No
Observable
Adverse
Effect
Level
(
8.5
mg
a.
i./
kg
bw/
day
for
short­
term
dermal
and
short­
term
inhalation)
6.
MOE
=
Margin
of
Exposure
=
No
Observable
Adverse
Effect
Level
(
NOAEL)
÷
ADD.
Short­
term
dermal
and
short­
term
inhalation
exposures
are
summed
and
divided
into
the
NOAEL.
The
dermal
and
inhalation
endpoints
are
the
same
and
identified
from
the
same
study
and
have
the
same
NOAELs.

A
MOE
of
100
is
adequate
to
protect
occupational
pesticide
handlers
from
short­
term
exposures
to
triflumizole;
therefore,
these
exposures
do
not
exceed
HED's
level
of
concern.

Post­
Application
Exposure
to
Agricultural
Workers:
There
is
a
potential
for
agricultural
workers
to
experience
post­
applications
exposures
to
pesticides
during
the
course
of
typical
agricultural
activities.
HED
in
conjunction
with
the
Agricultural
Re­
entry
Task
Force
(
ARTF)
has
identified
a
number
of
postapplication
agricultural
activities
that
may
occur.
HED
has
also
identified
Transfer
Coefficients
(
TCs)
expressed
as
cm
²
/
hr
which
help
describe
the
amount
of
foliar
dislodgeable
pesticide
residue
that
is
available
to
be
transferred
to
agricultural
workers
during
the
course
of
post­
application
agricultural
activities.

There
were
no
chemical
specific
data
with
which
to
estimate
post­
application
exposures
of
agricultural
workers
to
dislodgeable
residues
of
triflumizole.
Therefore,
theoretical
estimates
of
exposure,
based
on
10
surrogate
studies,
have
been
conducted.
The
ExpoSAC
[
Standard
Operating
Procedure
(
SOP)
003.1,
Rev.
7
Aug.
2000,
Regarding
Agricultural
Transfer
Coefficients;
Amended
ExpoSAC
Meeting
notes
­
13
Sept
01]
lists
a
number
of
possible
post­
application
agricultural
activities
relative
to
field
corn
that
result
in
pesticide
exposure
to
agricultural
workers.
TCs
expressed
as
cm
²
/
hr
are
identified
for
each
of
the
post­
application,
agricultural
activities.
The
TCs
are
derived
from
data
in
surrogate
exposure
studies
conducted
during
the
various
activities
listed.

The
highest
(
i.
e.,
most
conservative)
TC
relative
to
the
subject
crops
is
5,000
cm
²
/
hr
for
hand
harvest,
thinning
or
irrigation
activities
in
broccoli.
A
TC
of
2,500
cm
²
/
hr
is
identified
for
hand
harvest
or
thinning
of
collards,
leafy
greens,
kale
and
parsley.
For
this
assessment,
HED
uses
the
5,000
cm
²
/
hr
TC
as
a
Tier
I,
screening
level
figure.

The
transfer
coefficients
used
in
this
assessment
are
from
an
interim
transfer
coefficient
procedure
developed
by
HED's
Science
Advisory
Council
for
Exposure
using
proprietary
data
from
the
ARTF
database
(
SOP#
3.1).
It
is
the
intention
of
HED's
ExpSAC
that
this
procedure
will
be
periodically
updated
to
incorporate
additional
information
about
agricultural
practices
in
crops
and
new
data
on
transfer
coefficients.
Much
of
this
information
will
originate
from
exposure
studies
currently
being
conducted
by
the
ARTF,
from
further
analysis
of
studies
already
submitted
to
the
Agency,
and
from
studies
in
the
published
scientific
literature.

Post­
application
worker
exposure
is
estimated
using
HED
procedure
that
assumes
20%
of
the
application
rate
is
available
as
dislodgeable
foliar
residue
on
the
day
of
treatment.
HED
expects
postapplication
agricultural
exposures
to
scouts
(
i.
e.,
crop
advisors)
or
workers
involved
in
irrigation
would
typically
be
short­
term.
The
total
number
of
acres
treated
per
day
is
comparatively
small
and
treatment
is
not
expected
to
be
necessary
at
the
same
time
for
all
acres
on
a
given
farm,
therefore
scouting
after
treatment
will
occur
in
short­
term
periods
of
time.

PDR
t
=
DFR
t
*
CF1
*
Tc
*
ET
where:
PDR
t
=
potential
dose
rate
on
day
"
t"
(
mg/
day)
DFR
t
=
dislodgeable
foliar
residue
on
day
"
t"
(
µ
g/
cm2)
CF1
=
weight
unit
conversion
factor
to
convert
µ
g
units
in
DFR
value
to
mg
for
the
daily
dose
(
0.001
mg/
µ
g)
TC
=
transfer
coefficient
(
cm2/
hr)
(
In
this
case
5,000
cm2/
hr;
ExpoSAC
SOP
003.1
Rev.
7
Aug.
2000;
amended
13
Sept
01
ExpoSAC
meeting
Notes).
ET
=
Exposure
Time
(
hrs)
(
8)

and
DFR
t
=
AR
*
F
*
(
1­
D)
t
*
CF2
*
CF3
where:

AR
=
Application
rate
(
lb
a.
i./
A)
(
0.1875
lb
a.
i./
A)
F
=
fraction
of
a.
i.
retained
on
foliage
(
unitless)
D
=
fraction
of
residue
that
dissipates
daily
(
unitless)
t
=
postapplication
day
on
which
exposure
is
being
assessed
CF2
=
weight
unit
conversion
factor
to
convert
the
lbs
a.
i.
in
the
application
rate
to
µ
g
for
the
DFR
value
(
4.54
x
108
µ
g/
lb)
CF3
=
Area
unit
conversion
factor
to
convert
the
surface
area
units
(
ft2)
in
the
application
rate
to
cm2
for
the
DFR
value
(
1.08
x
10­
3
ft2/
cm2
or
2.47
x
10­
8
acre/
cm2
if
the
application
rate
is
per
acre).

 
DFR
=
0.1875
lb
a.
i./
A
*
0.20
*
(
1­
0)
0
*
4.54
x
108
µ
g
a.
i./
lb
*
2.47
x
10­
8A/
cm2
=
0.42
µ
g/
cm2
PDR
=
042
µ
g/
cm2
*
0.001
mg/
µ
g
*
5,000
cm2/
hr
*
8
hr/
day
=
16.8
mg
a.
i./
day
*
3.5
%
dermal
absorption
÷
60
kg
bw
=
0.0098
mg
a.
i./
kg
bw/
day
Margin
of
Exposure
(
MOE)
=
NOAEL
÷
PDR
 
8.5
mg
a.
i./
kg
bw/
day
÷
0.0098
mg
a.
i./
kg
bw/
day
=
870.

An
MOE
of
100
is
adequate
to
protect
agricultural
workers
from
post­
application
exposure
to
triflumizole.
The
calculated
MOEs
>
100
therefore
this
use
does
not
exceed
HED's
level
of
concern.
11
OTHER
CONSIDERATIONS
Residue
Chemistry
Triflumizole
is
an
imidazole
fungicide
that
inhibits
ergosterol
biosynthesis
in
fungi.
Ergosterol
is
a
sterol
which
is
thought
to
function
as
a
stabilizer
for
the
membranes
that
make
up
the
cell
wall
of
fungi.
Permanent
tolerances
are
established
under
40
CFR
§
180.476(
a)
for
the
combined
residues
of
triflumizole
and
its
metabolites
containing
the
4­
chloro­
2­
trifluoromethylaniline
moiety,
calculated
as
the
parent
compound,
in/
on
apples,
cherries,
grapes,
pears,
strawberries,
and
cucurbit
vegetables.
In
addition
permanent
tolerances
for
livestock
commodities
have
been
established
under
40
CFR
§
180.476(
b)
for
the
combined
residues
of
triflumizole,
the
metabolite
4­
chloro­
2­
hydroxy­
6­
trifluoromethylaniline
sulfate,
and
other
metabolites
containing
the
4­
chloro­
2­
trifluoromethylaniline
moiety,
calculated
as
the
parent
compound,
in/
on
milk;
eggs;
meat,
fat,
and
meat
byproducts
(
mbyp)
of
cattle,
goats,
hogs,
horses,
and
sheep;
and
in/
on
meat,
and
mbyp
of
poultry.
A
time­
limited
tolerance
in
conjunction
with
an
Section
18
Emergency
Exemption
has
been
established
under
40
CFR
§
180.476(
a)
for
the
combined
residues
of
triflumizole
and
its
metabolites
containing
the
4­
chloro­
2­
trifluoromethylaniline
moiety,
calculated
as
the
parent
compound,
in/
on
filberts.

Summary
of
Proposed
Use:
See
Attachment
2
for
a
summary
of
the
proposed
use
pattern.
A
rotational
crop
restriction
is
not
included
on
the
label.
The
label
should
be
amended
to
include
the
following
plantback
intervals
(
PBIs)
for
rotational
crops:
30
days
for
leafy
vegetables,
and
60
days
for
root
vegetables.
Rotation
to
all
other
crops
is
prohibited.
Provided
these
amendments
are
made,
the
application
scenario
is
adequately
described.

Nature
of
the
Residue
­
Plants
and
Livestock:
The
nature
of
the
residue
in
fruit
is
adequately
understood
based
on
acceptable
metabolism
data
on
apples,
cucumbers,
grapes,
and
pears.
The
results
of
metabolism
studies
were
extensively
discussed
in
connection
with
PP#
5G3232
(
Memo,
N.
Dodd,
7/
3/
85).
HED
concluded
that
the
residues
of
concern
in/
on
apples,
pears,
cucumbers
and
grapes
include
the
parent
compound,
triflumizole
and
its
metabolites
(
free
and
conjugates)
containing
the
4­
chloro­
2­
trifluormethyaniline
moiety
(
calculated
as
triflumizole).
In
a
meeting
on
2/
26/
02,
HED
MARC
concluded
that
there
was
no
need
to
revisit
the
residues
of
concern
in
primary
crops
(
Memo,
J.
Tyler,
3/
13/
02;
D280869).
The
MARC
concurred
with
the
current
tolerance
expression
for
plants
as
stated
in
40
CFR
§
180.476.

There
are
no
livestock
feed
items
associated
with
the
proposed
uses;
therefore,
a
discussion
of
potential
transfer
of
secondary
residues
to
livestock
commodities
is
not
relevant
to
this
petition.

Storage
Stability:
No
storage
stability
data
were
submitted
to
support
the
current
action.
Previously
reviewed
data
indicate
that
triflumizole
is
stable
for
up
to
10
months
in
frozen
cucurbits
vegetables
(
MRID
449713­
01
thru
­
03;
Memo,
J.
Tyler,
3/
11/
02;
D271003)
and
strawberries
(
MRID
45375406;
J.
Tyler,
3/
11/
02;
D274589)
and
up
to
­
12
months
in
frozen
cherries
(
MRID
44438401;
Memo,
J.
Tyler,
4/
30/
01;
D242429)
and
apples
and
grapes
(
MRID
41131203;
Memo,
S.
Malak,
1/
25/
90,
DEB#
s
5479
&
5480).
These
data
support
the
submitted
residue
studies
on
turnips,
leaf
lettuce
and
broccoli
in
which
the
samples
were
analyzed
within
66,
125,
and
65
days
of
sampling,
respectively.

Magnitude
of
the
Residue
­
Plants:
TDA
cited
the
results
of
crop
field
trial
studies
performed
on
turnip
leaves,
leaf
lettuce
and
broccoli
in
Texas
in
2003
(
Region
6;
one
field
trial
per
study).
These
12
studies
have
been
submitted
to
the
Agency,
and
HED
has
completed
a
preliminary
review
of
these
studies.

Turnip
Leaves
(
MRID#
46212401):
Residues
of
triflumizole
were
4.30
ppm,
8.87
ppm,
and
8.11
ppm
(
average
7.09
ppm)
in
turnip
leaf
samples
collected
1
day
following
the
last
of
5
applications
of
Procure
®
50WS
at
0.25
lb
a.
i./
A
[
total
application
rate
of
2.5
lb.
a.
i./
A;
7­
day
retreatment
interval
(
RTI);
ground
airblast
applications].

Leaf
Lettuce
(
MRID#
46212402):
Residues
of
triflumizole
were
4.76
ppm,
5.84
ppm,
and
6.25
ppm
(
average
5.62
ppm)
in
leaf
lettuce
samples
collected
1
day
following
the
last
of
5
applications
of
Procure
®
50WS
at
0.25
lb
a.
i./
A
(
total
application
rate
of
2.5
lb.
a.
i./
A;
7­
day
RTI;
ground
airblast
applications).

Broccoli
(
MRID#
46212403):
Residues
of
triflumizole
were
0.323
ppm,
0.864
ppm,
and
0.926
ppm
(
average
0.704
ppm)
in
broccoli
samples
collected
1
day
following
the
last
of
5
applications
of
Procure
®

50WS
at
0.25
lb
a.
i./
A
(
total
application
rate
of
2.5
lb.
a.
i./
A;
7­
day
RTI;
ground
airblast
applications).

The
available
residue
data
show
that
residues
of
triflumizole
are
#
8.87
ppm
in
turnip
leaves,
leaf
lettuce
and
broccoli
when
treated
with
a
total
of
1.25
lb
a.
i./
A/
year
(
5
applications
of
0.25
lb.
a.
i./
A/
application)
with
a
RTI
of
7
days
and
preharvest
inteveral
(
PHI)
of
1
day.
Although
the
application
rates
made
at
5x
the
proposed
application
rate,
the
submitted
data
are
adequate
and
support
time­
limited
tolerances
for
the
combined
residues
of
triflumizole
and
its
metabolites
containing
the
4­
chloro­
2­
trifluoromethylaniline
moiety,
calculated
as
the
parent
compound,
in/
on
the
following
RACs:
parsley,
leaves
at
9.0
ppm;
dandelion,
leaves
at
7.0
ppm;
Swiss
chard
at
7.0
ppm;
collards
at
9.0
ppm;
kale
at
9.0
ppm;
kohlrabi
at
9.0
ppm;
mustard
greens
at
9.0
ppm;
Napa
cabbage
at
9.0
ppm;
broccoli
at
1.0
ppm;
and
cilantro
at
9.0
ppm.

Magnitude
of
the
Residue
­
Livestock:
As
there
are
no
livestock
feed
items
associated
with
the
proposed
uses,
data
on
residues
of
triflumizole
in
livestock
tissues,
milk
and
eggs
are
not
required
to
support
the
current
action.

Residues
in
Rotational
Crops:
Results
of
confined
and
limited
field
rotational
crop
studies
were
reviewed
in
the
HED
memoranda
dated
3/
11/
02
(
Memo,
J.
Tyler;
D274589).
HED
concluded
that
the
following
PBIs
are
appropriate:
30
days
for
leafy
vegetables,
and
60
days
for
root
vegetables.
Because
quantifiable
residues
were
found
in
wheat
commodities
at
the
longest
adequate
PBI
tested
(
120
days),
rotation
to
wheat
and
all
other
crops
is
not
permitted.
The
petitioner
should
submit
adequate
limited
field
rotational
crop
data
on
wheat
at
PBIs
longer
than
120
days.
Alternatively,
the
petitioner
has
the
option
of
submitting
a
full
set
of
residue
field
trials
on
all
intended
rotational
crops
other
than
leafy
and
root
vegetables.
The
petitioner
should
amend
the
proposed
Section
B
to
specify
the
aforementioned
rotational
crop
restrictions.

Analytical
Enforcement
Method
­
Plants
and
Livestock:
The
methods
used
in
the
crop
field
trials
are
suitable
for
data
gathering
purposes.
The
gas
chromatography/
mass
selective
detector
(
GC/
MSD)
method
(
Morse
Method
METH­
115,
Revision
#
3)
used
in
the
turnip,
leaf
lettuce,
and
broccoli
crop
field
trials
has
a
validated
limit
of
quantitation
(
LOQ)
of
0.05
ppm.
Morse
Method
METH­
115,
Revision
#
3
converts
residues
of
triflumizole
and
its
aniline­
containing
metabolites
to
4­
chloro­
2­
13
trifluoromethylaniline
(
FA­
1­
1)
which
is
then
quantified
as
triflumizole
equivalents.
A
similar
GC/
NPD
method
has
been
deemed
acceptable
as
a
tolerance
enforcement
method
in
conjunction
with
a
petition
for
use
on
apples,
grapes,
and
pears,
and
has
been
forwarded
to
FDA
for
inclusion
in
the
Pesticide
Analytical
Manual
(
PAM),
Volume
II
as
Method
I
(
G.
Kramer,
12/
16/
94).
For
the
purposes
of
this
petition,
HED
concludes
that
the
current
enforcement
method
is
appropriate
for
enforcement
of
the
tolerance
associated
with
this
petition.

There
are
no
livestock
feed
items
associated
with
the
proposed
uses;
therefore,
data
collection
and
tolerance
enforcement
methods
for
livestock
commodities
are
not
required
for
the
establishment
of
a
tolerance
for
triflumizole
residues
in/
on
the
proposes
uses.
However,
adequate
methods
are
available
for
determining
residues
of
triflumizole,
its
sulfate
metabolite,
and
other
metabolites
containing
the
4­
chloro­
2­
trifluromethylaniline
moiety
in
livestock
commodities.
These
methods
are
listed
as
Methods
II
and
III
in
PAM­
II.

Multiresidue
Methods:
The
Food
and
Drug
Administration
(
FDA)
PESTDATA
database
(
PAM
Volume
I,
Appendix
I,
3rd
edition,
1994)
indicates
that
triflumizole
is
completely
recovered
(>
80%)
by
Multiresidue
Protocol
D
(
PAM
I
Sections
232.4).

cc:
J.
Tyler
(
RAB1),
R.
Mitkus
(
RAB1),
M.
Dow
(
RAB1)
Branch
(
12/
15/
04),
PV
Shah
(
1/
28/
05)
J.
Tyler:
809B:
CM#
2:
(
703)
305­
5564:
7509C:
RAB1
14
Attachment
1.
Updated
Toxicology
Tables.

Toxicity
Profile
of
Triflumizole
Technical.

Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
rodents
(
rat)
45498001
(
1980)
Acceptable/
guideline
0,
20,
200,
2000
ppm
M:
0,
1.4,
15.3,
or
176.5
mg/
kg/
day
F:
0,
1.8,
17.2,
or
217.9
mg/
kg/
day
NOAEL
=
Males:
15.3
mg/
kg/
day;
Females:
17.2
mg/
kg/
day
LOAEL
=
Males:
176.5
mg/
kg/
day;
Females:
217.9
mg/
kg/
day
based
on
increased
kidney
and
liver
weights
and
the
accumulation
of
fat
droplets
in
the
liver.

870.3100
90­
Day
oral
toxicity
rodents
(
mouse)
45498002
(
1980)
Acceptable/
guideline
0,
20,
200,
2000
ppm
M:
0,
3.2,
33.1,
or
380.7
mg/
kg/
day
F:
0,
4.2,
42.6,
or
466.2
mg/
kg/
day
NOAEL
=
Males:
33.1
mg/
kg/
day;
Females:
42.6
mg/
kg/
day
LOAEL
=
Males:
380.7
mg/
kg/
day;
Females
466.2
mg/
kg/
day
based
on
reduced
growth.

870.3150
90­
Day
oral
toxicity
in
nonrodents
NA
NA
870.3200
21/
28­
Day
dermal
toxicity
(
rat)
41706601
(
1990)
Acceptable/
guideline
0,
10,
100,
or
1000
mg/
kg/
day
6
hr/
day,
7
d/
week
NOAEL
$
1000
mg/
kg/
day
LOAEL
=
not
identified
870.3250
90­
Day
dermal
toxicity
NA
NA
870.3465
90­
Day
inhalation
toxicity
NA
NA;
28­
day
inhalation
toxicity
is
data
gap
870.3700a
Prenatal
developmental
in
rodents
(
rat)
45458001
(
1983)
Acceptable/
guideline
when
considered
with
MRIDs
00157075
and
00164384
F:
0,
10,
35,
or
120
mg/
kg/
day
Maternal
NOAEL
=
10
mg/
kg/
day
LOAEL
=
35
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption,
and
increased
placental,
spleen
and
liver
weights.
Developmental
NOAEL
=
10
mg/
kg/
day
LOAEL
=
35
mg/
kg/
day
based
on
decreased
numbers
of
viable
fetuses,
increased
dead
or
resorbed
fetuses,
increased
numbers
of
late
resorptions,
decreased
fetal
body
weight,
and
increased
incidences
of
cervical
ribs.

870.3700a
Prenatal
developmental
in
rodents
(
rat)
00157075
(
1986)
Acceptable/
non­
guideline
(
complimentary)
F:
0
or
3
mg/
kg/
day
Must
be
considered
with
MRID
45458001
LOAELs/
NOAELs
not
assigned
870.3700a
Prenatal
developmental
in
rodents
(
rat)
00164384
(
1986)
Acceptable/
non­
guideline
(
repeat)
F:
0,
3,
7,
or
35
mg/
kg/
day
Must
be
considered
with
MRID
45458001
LOAELs/
NOAELs
not
assigned
870.3700b
Prenatal
developmental
in
nonrodents
(
rabbit)
00156546
(
1985)
Acceptable/
guideline
F:
0,
50,
100,
or
200
mg/
kg/
day
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
100
mg/
kg/
day
based
on
decreased
body
weight
gains,
food
consumption,
and
placental
weights.
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
100
mg/
kg/
day
based
on
decreased
24­
hour
survival,
decreased
placental
weights,
and
increased
fetal
and
litter
incidences
of
lumbar
ribs.

870.3700b
Prenatal
developmental
in
nonrodents
(
rabbit)
40752003
(
1988)
Unacceptable/
guideline
F:
0,
5,
25,
or
50
mg/
kg/
day
Must
be
considered
with
MRID
00156546
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
not
identified
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
not
identified
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
15
870.3800
Reproduction
and
fertility
effects
(
rat)
00156547
(
1984)
Unacceptable/
guideline
0,
70,
170,
or
420
ppm
P:
0,
3.5,
8.5,
or
21
mg/
kg/
day
Must
be
considered
with
MRID
00162176
a
Parental/
Systemic
NOAEL
=
8.5
mg/
kg/
day
LOAEL
=
21
mg/
kg/
day
based
on
decreased
body
weight
and
overall
body
weight
gain,
increased
relative
liver
weights,
and
increased
mortality
in
females.
Reproductive
NOAEL
=
not
identified
LOAEL
=
3.5
mg/
kg/
day
based
on
based
on
increased
gestation
length
in
P.
Offspring
NOAEL
=
8.5
mg/
kg/
day
LOAEL
=
21
mg/
kg/
day
based
on
decreased
pup
body
weight,
survival
indices,
and
litter
sizes
and
a
slight
increased
incidence
of
hydronephrosis
in
F
1a
pups.

870.3800
Reproduction
and
fertility
effects
(
rat)
00162176
(
1986)
00156548
(
1984)
40301602
(
1987)
Acceptable/
guideline
with
MRID
00156547
0,
30,
70,
or
170
ppm
P:
0,
1.5,
3.5,
or
8.5
mg/
kg/
day
Parental/
Systemic
NOAEL
=
8.5
mg/
kg/
day
LOAEL
=
not
established
Reproductive
NOAEL
=
1.5
mg/
kg/
day
LOAEL
=
3.5
mg/
kg/
day
based
on
based
on
increased
gestation
length
in
dams
of
the
F
3a
interval.
Offspring
NOAEL
=
3.5
mg/
kg/
day
LOAEL
=
8.5
mg/
kg/
day
based
on
decreased
pup
weights,
survival
indices,
and
litter
sizes
in
both
F
3
litters,
reduced
litter
size
in
the
F
1a
litter,
increased
total­
litter
mortality
in
the
F
3a
litter,
and
developmental
effects
in
the
F
1b
and
F
2b
progeny.

870.4100a
Chronic
toxicity
rodents
NA;
see
870.4300
NA
870.4100b
Chronic
toxicity
nonrodents
(
dog)
00149848
(
1984)
Acceptable/
guideline
0,
100,
300,
or
1000
ppm
M:
0,
3.33,
10.00,
or
34.10
mg/
kg/
day
F:
0,
3.27,
10.69,
or
35.17
mg/
kg/
day
NOAEL
=
Males:
10.00
mg/
kg/
day;
Females:
10.69
mg/
kg/
day
LOAEL
=
Males:
34.10
mg/
kg/
day;
Females:
35.17
mg/
kg/
day
based
on
increased
alkaline
phosphatase
activity
and
a
mild,
macrocytic
anemia
in
males,
increased
absolute
and
relative
liver
weights
in
both
sexes,
and
on
macroscopic
findings
in
the
liver
of
both
sexes.

870.4200a
Carcinogenicity
(
rat)
NA;
see
870.4300
NA
870.4200b
Carcinogenicity
(
mouse)
00156544
(
1984)
Acceptable/
guideline
0,
100,
400,
or
1600
ppm
M:
0,
16.2,
67.4,
or
296.1
mg/
kg/
day
F:
0,
21.7,
86.1,
or
362.2
mg/
kg/
day
NOAEL
=
Males:
16.2
mg/
kg/
day;
Females:
21.7
mg/
kg/
day
LOAEL
=
Males:
67.4
mg/
kg/
day;
Females:
86.1
mg/
kg/
day
based
on
microscopic
lesions
of
the
liver.
No
evidence
of
carcinogenicity
870.4300
Combined
Chronic/
oncogenicity
(
rat)
00156545
(
1984)
40301604
(
1987)
Acceptable/
guideline
0,
100,
400,
or
1600
ppm
M:
0,
3.5­
3.7,
14.1­
15.1,
or
59.4­
62.0
mg/
kg/
day
F:
0,
4.5­
4.6,
18.0­
18.1,
or
77.0­
78.0
mg/
kg/
day
NOAEL
=
Males:
<
3.5­
3.7
mg/
kg/
day;
Females:
<
4.5­
4.6
mg/
kg/
day
LOAEL
=
Males:
3.5­
3.7
mg/
kg/
day;
Females:
4.5­
4.6
mg/
kg/
day
based
on
liver
toxicity
(
eosinophilic
foci
in
male
rats
and
fatty
vacuolation
and
inflammation
and
necrosis
in
female
rats).
No
evidence
of
carcinogenicity.

870.5100
Bacterial
reverse
mutation
40494409
(
1987)
Acceptable
seven
concentrations
ranging
from
5
to
5000
:
g/
plate
Negative
with
or
without
S9
activation
at
5000
:
g/
plate
and
less.

870.5100
Bacterial
reverse
mutation
45502203
(
1983)
Acceptable
concentrations
ranging
from
8
to
8000
:
g/
plate
Negative
with
or
without
S9
activation
at
8000
:
g/
plate
and
less.

870.5375
In
vitro
mammalian
chromosome
abberation
(
CHL)
40494408
(
1987,
1988)
Acceptable
5
to
40
:
g/
mL
Negative
with
or
without
S9.

870.5395
In
vitro
mammalian
cytogenetics
(
mouse
bone
marrow)
00160620
(
1986)
Acceptable
M&
F:
160,
533
and
1600
mg/
kg
(
single
oral
dose)
Negative.
Not
clastogenic
for
the
production
of
micronuclei
in
bone
marrow
polychromatic
erythrocytes
in
mice
at
single
oral
doses
up
to
1600
mg/
kg.
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
16
870.5500
DNA
damage/
repair
REC
assay
45502204
(
1983)
Unacceptable
concentrations
range
from
24
to
24,000
mg/
disk
Negative.
No
evidence
of
DNA
damage
up
to
24,000
mg/
disk.
Study
is
unacceptable
because
a
metabolic
activation
system
was
not
used.

870.5550
UDS
in
primary
rat
hepatocytes
45502205
(
1984)
Acceptable
12.5
to
30
:
g/
mL
Negative.
No
evidence
of
unscheduled
DNA
synthesis
up
to
cytotoxic
concentrations.

870.6200a
Acute
neurotoxicity
screening
battery
46202501
(
2003)
Acceptable
M:
0,
25,
100,
400
mg/
kg/
day
F:
0,
25,
100,
200
mg/
kg/
day
NOAEL
=
25
mg/
kg/
day
LOAEL
=
100
mg/
kg
bw/
day,
based
on
FOB
findings
(
neuromuscular
impairment)
and
decreased
locomotor
activity
870.6200b
Subchronic
neurotoxicity
screening
battery
46202502
(
2004)
Unacceptable
M:
0,
4.10,
40.9
or
117.3
mg/
kg/
day
F:
0,
4.88,
47.8
or
133.3
mg/
kg/
day
NOAEL
=
117.3/
133.3
(
M/
F)
mg/
kg/
day
LOAEL
=
not
established
Study
is
unacceptable
because
of
lack
of
positive
control
data
870.6300
Developmental
neurotoxicity
NA
NA
870.7485
Metabolism
and
pharmacokinetics
(
rat)
40789101
(
1988)
Acceptable/
guideline
with
41606201
and
41606202
M&
F:
10
mg/
kg
as
single
oral
dose
Following
oral
treatment
of
rats
with
[
phenyl­
U­
14C]­
NF­
114,
no
sex­
related
differences
were
observed
in
absorption,
metabolism,
distribution
or
excretion.
Maximum
concentrations
of
radioactivity
in
plasma
were
attained
within
1
hour
of
dosing
in
both
sexes.
Low
levels
of
radioactivity
were
detectable
in
all
tissue,
organ,
and
blood
samples.
Radioactivity
in
urine
accounted
for
69.5­
74.4%
of
the
dose
and
feces
accounted
for
21.7­
21.9%
of
the
dose.
Based
on
the
metabolite
profile,
the
metabolism
in
rats
primarily
involves
oxidation
to
FM­
8­
1
and
FA­
1­
5,
followed
by
sulfation
and
glucuronidation.

870.7485
Metabolism
and
pharmacokinetics
(
rat)
41606201
(
1983)
41606202
(
1984)
Acceptable/
guideline
with
40789101
M&
F:
10
or
300
mg/
kg
as
single
oral
dose
Following
oral
treatment
of
rats
with
[
phenyl­
U­
14C]­
NF­
114,
approximately
93.8­
100.6%
of
the
administered
dose
was
recovered.
Urine
was
the
major
route
of
excretion.
Low
levels
of
radioactivity
were
detectable
in
all
tissue,
organ,
and
blood
samples
collected
2
days
(
10
mg/
kg
group)
or
4
days
(
300
mg/
kg
group)
post­
dose
with
tissue
concentrations
generally
higher
in
males
than
females.
The
metabolite
profile
in
the
excreta
was
quantitatively
and
qualitatively
similar
between
the
sexes
and
dose
groups.
Based
on
the
metabolite
profile,
the
biotransformation
of
NF­
114
in
rats
primarily
involved
oxidation
of
parent
to
FM­
8­
1
and
FA­
1­
5,
followed
by
conjugation
yielding
sulfate
and
glucuronic
acid
conjugates.

870.7600
Dermal
penetration
NA
NA
Special
studies
Hepatic
enzyme
induction
40830401
(
1988)
Acceptable/
nonguideline
M&
F:
0
or
200
mg/
kg/
day
as
oral
dose
for
five
consecutive
days
The
study
provides
evidence
that
triflumizole
induces
hepatic
microsomal
enzymes
when
administered
orally.
However,
no
correlation
between
the
increased
enzyme
activities
and
hepatic
lesions
observed
following
chronic
administration
was
made
since
no
histopathology
was
performed.

Summary
of
Toxicological
Dose
and
Endpoints
for
Triflumizole
for
Use
in
Human
Risk
Assessment1.
17
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
females
13­
50
years
of
age
NOAEL
=
10
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.1
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
0.1
mg/
kg/
day
Developmental
Toxicity
Study
­
Rat
Developmental
LOAEL
=
35
mg/
kg/
day
based
on
decreased
numbers
of
viable
fetuses,
increased
dead
or
resorbed
fetuses,
increased
numbers
of
late
resorptions,
decreased
fetal
body
weight,
and
increased
incidences
of
cervical
ribs.

Acute
Dietary
general
U.
S.
population
(
including
infant
and
children)
NOAEL
=
25
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.25
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
0.03
mg/
kg/
day
Acute
Neurotoxicity
Study
­
Rat
LOAEL
=
100
mg/
kg/
day
based
on
FOB
findings
(
neuromuscular
impairment)
and
decreased
locomotor
activity
.

Chronic
Dietary
all
populations
NOAEL=
1.5
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.015
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.015
mg/
kg/
day
Multi­
generation
Reproduction
Study
­
Rat
Reproductive
LOAEL
=
3.5
mg/
kg/
day
based
on
increased
gestation
length
in
dams
of
the
F3a
interval.

Short­
Term
Oral
(
1­
30
days)

(
Residential)
oral
NOAEL=
8.5
mg/
kg/
day
LOC
for
MOE
=
100
(
Residential,
includes
the
FQPA
SF)
Multi­
generation
Reproduction
Study
­
Rat
LOAEL
=
21
mg/
kg/
day,
based
on
decreased
body
weight
gain
in
pups
during
lactation.

Intermediate­
Term
Oral
(
1­
6
months)

(
Residential)
oral
NOAEL=
8.5
mg/
kg/
day
LOC
for
MOE
=
100
(
Residential,
includes
the
FQPA
SF)
Multi­
generation
Reproduction
Study
­
Rat
LOAEL
=
21
mg/
kg/
day,
based
on
decreased
body
weight
gain
in
pups
during
lactation
and
decreased
body
weight
and
body
weight
gain
in
parental
animals.

Short­
Term
Dermal
(
1­
30
days)

(
Occupational/
Residential)
oral
NOAEL=
8.5
mg/
kg/
day
(
dermal
absorption
rate
=
3.5%)
LOC
for
MOE
=
100
(
Occupational)

LOC
for
MOE
=
100
(
Residential,
includes
the
FQPA
SF)
Multi­
generation
Reproduction
Study
­
Rat
LOAEL
=
21
mg/
kg/
day,
based
on
decreased
body
weight
gain
in
pups
during
lactation.

Intermediate­
and
Long­
Term
Dermal
(
1­
6
months
and
6
month
or
longer)

(
Occupational/
Residential)
oral
NOAEL=
1.5
mg/
kg/
day
(
dermal
absorption
rate
=
3.5%)
LOC
for
MOE
=
100
(
Occupational)

LOC
for
MOE
=
100
(
Residential,
includes
the
FQPA
SF)
Multi­
generation
Reproduction
Study
­
Rat
LOAEL
=
3.5
mg/
kg/
day
based
on
increased
gestation
length
in
the
dams
of
the
F3a
interval.
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
18
Short­
Term
Inhalation
(
1­
30
days)

(
Occupational/
Residential)
oral
NOAEL=
8.5
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
LOC
for
MOE
=
100
(
Occupational)

LOC
for
MOE
=
100
(
Residential,
includes
the
FQPA
SF)
Multi­
generation
Reproduction
Study
­
Rat
LOAEL
=
21
mg/
kg/
day,
based
on
decreased
body
weight
gain
in
pups
during
lactation.

Intermediate­
and
Long­
Term
Inhalation
(
1­
6
months
and
6
month
or
longer)

(
Occupational/
Residential)
oral
NOAEL=
1.5
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
LOC
for
MOE
=
100
(
Occupational)

LOC
for
MOE
=
100
(
Residential,
includes
the
FQPA
SF)
Multi­
generation
Reproduction
Study
­
Rat
LOAEL
=
3.5
mg/
kg/
day
based
on
increased
gestation
length
in
the
dams
of
the
F3a
interval.

Cancer
(
oral,
dermal,
inhalation)
evidence
for
noncarcinogenicity
for
humans
Not
applicable
Combined
Chronic
Toxicity/
Carcinogenicity
Study
­
Rat
Carcinogenicity
Study
­
Mouse
No
evidence
of
carcinogenicity
in
rats
and
mice.

1
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern.
19
Attachment
2.
Summary
of
Proposed
Use
Pattern.

Crop
Site
broccoli,
cilantro,
collards,
dandelion,
kale,
kohlrabi,
mustard
greens,
Napa
cabbage,
parsley,
Swiss
chard
in
Texas
Pest
powdery
mildew
A.
I.
triflumizole
[
1­[
1­((
4­
chloro­
2­(
trifluoromethyl)
phenyl)
imino)
­
2­
propoxyethyl]­
1Himidazole

Formulation
Procure
®
50
WS
Fungicide,
EPA
Reg.
No.
400
­
431,
50
%
a.
i.
powder.

Application
Method
groundboom,
aerial
Application
Rate
0.1875
lb
a.
i./
A
Application
Number
not
specified
Application
Maximum
0.5
lb
a.
i./
A/
yr.

Application
Interval
10
­
14
days
(
do
not
apply
more
than
2
sequential
applications)

PHI
1
days
Maximum
acres
treated
3,000
possible
Maximum
a.
i.
used
1,125
lb
active
ingredient
if
all
acres
are
treated
2
times
at
the
maximum
rate
Manufacturer
Gowan
Company
Rotational
Crop
Restrictions
Not
specified
Restrictions
°
No
more
than
two
sequential
applications
without
at
least
one
intervening
application
of
an
alternative
registered
fungicide
for
powdery
mildew
control
is
allowed.
°
Applications
through
any
type
of
irrigation
system
is
prohibited.