Document ID: EPA-HQ-OPP-2006-0297-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-21T04:00Z

FILE
NAME:
company.
wpt
(
7/
1/
2003)
(
xml)

COMPANY
FEDERAL
REGISTER
DOCUMENT
SUBMISSION
TEMPLATE
(
7/
1/
2003)

EPA
Registration
Division
contact:
[
James
Tompkins,
703­
305­
5697]

Summary
of
Petitions
The
petitioner
summary
of
the
pesticide
petitions
is
printed
below
as
required
by
FFDCA
section
408
(
d)
(
3).
The
summary
of
the
petitions
is
prepared
by
the
petitioner
and
represents
the
view
of
the
petitioner.
The
petition
summary
announces
the
availability
of
the
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues
or
an
explanation
of
why
no
such
method
is
needed.

[
Interregional
Research
Project
Number
4
(
IR­
4)]

[
PP#
5E
xxx
(
Garden
Beets
and
Spinach)
­
to
be
assigned]

EPA
has
received
pesticide
petition
([
5E
xxxx)
from
[
IR­
4],
[
681
Highway
1
South,
North
Brunswick,
NJ
08902­
3390]
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
180.353
by
establishing
tolerances
for
residues
of
[
the
herbicide
desmedipham
(
ethyl­
m­
hydroxycarbanilate
carbanilate)
in
or
on
the
raw
agricultural
commodities:
[
beets,
garden,
tops
at
1
.0
ppm,
beets,
garden,
roots
at
0.05
ppm,
and
spinach
at
6
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.
This
notice
includes
a
summary
of
the
petitions
prepared
by
Bayer
CropScience,
P.
O.
Box
12014,
2
T.
W.
Alexander
Drive,
Research
Triangle
Park,
NC
27709.

A.
Residue
Chemistry
1.
Plant
and
Animal
metabolism.
[
The
metabolism
of
desmedipham
in
plants
is
adequately
understood.
Studies
have
been
conducted
extensively
in
sugar
beets.
The
major
terminal
residues
consist
of
desmedipham
and
its
hydrolysis
product,
ethyl
3­
hydroxyphenylcarbamate
(
EHPC).
The
residue
of
concern
for
tolerances
setting
purposes
is
desmedipham.
The
nature
of
desmedipham
residues
in
livestock
is
well
understood
in
ruminants
and
hens.
A
dairy
cow
was
administered
[
14C]­
desmedipham
for
four
consecutive
days
at
a
rate
approximately
700
times
the
maximum
expected
daily
intake.
No
parent
compound
was
identified
in
milk,
liver
and
kidney.
Ethyl­
N­
3­
hydroxyphenylcarbamate
(
EHPC)
was
identified
as
a
major
component
and
3­
acetamidophenol
and
3­
aminophenol
(
liver
only)
as
minor
components.
Trace
levels
of
desmedipham,
EHPC
and
3­
2
acetamidophenol
were
detected
in
fat.
Laying
hens
were
administered
[
14C]­
desmedipham
for
ten
consecutive
days
at
a
dose
equivalent
to
approximately
12,500
times
the
maximum
estimated
daily
intake.
Excretion
of
the
dose
was
rapid
and
residues
were
very
low
in
all
tissues.
The
major
metabolites
identified
in
were
3­
aminophenol
and
EHPC
in
egg
yolk
with
trace
amounts
of
3­
acetamidophenol
and
desmedipham.
In
liver,
EHPC
was
the
only
metabolite
identified.
Desmedipham
residues
at
the
maximum
expected
1x
dietary
burden
for
animals
are
predicted
to
be
low
(<
0.01
ppm)
that
no
tolerances
are
required
for
meat,
milk,
poultry
and
eggs.]

2.
Analytical
method.
[
Analytical
methods
have
been
developed
and
validated
for
the
determination
of
desmedipham
in
or
on
sugar
beet.
The
method
employed
is
the
same
as
Method
I
in
Pesticide
Analytical
Manual
(
PAM)
Vol.
II.
Desmedipham
is
treated
with
alkali
and
the
hydrolysate
is
steam
distilled,
extracted
and
brominated
in
aqueous
acid.
The
resulting
brominated
compound
is
analyzed
by
gas
chromatography
equipped
with
an
electron
capture
detector
(
GC­
ECD).
The
method
limit
of
quantitation
is
0.1
ppm.
In
addition,
compound
specific
methods
that
extracted
desmedipham
from
sugar
beets,
cleaned­
up
with
florisil
and
C18
cartridge,
and
quantified
by
HPLCUV
detector
have
also
been
developed
and
validated.
Recently,
compound
specific
methods
that
extracted
and
quantified
desmedipham
from
sugar
beets
with
LC­
MS/
MS
detector
have
been
developed
and
validated.
The
method
(
LC­
MS/
MS)
limit
of
quantitation
is
0.05
ppm.
Therefore,
adequate
analytical
methodology
is
available
for
enforcement
purpose
and
it
allows
detection
of
residues
at
or
above
the
proposed
tolerances.
Enforcement
analytical
methods
for
residues
in
animal
commodities
are
not
needed
because
tolerances
for
animal
commodities
are
not
required.]

3.
Magnitude
of
residues
[
Beets,
Garden
 
IR
4
received
requests
from
the
states
of
Arkansas,
California,
Florida,
Michigan,
Massachusetts,
New
York,
North
Dakota,
Ohio,
Oregon,
Washington,
and
Wisconsin
for
the
use
of
desmedipham
on
garden
beets.
In
support
of
the
requests,
six
crop
field
trials
were
conducted
in
New
York,
Michigan,
Wisconsin,
Texas,
Oregon
and
Washington
that
encompassing
four
NAFTA
Regions.
Samples
were
analyzed
for
desmedipham
residues
using
an
HPLC/
UV
method
that
was
adequate
for
data
collection
purposes.
The
lowest
level
of
method
validation
(
LLMV)
for
desmedipham
in/
on
beet
top
and
root
was
0.05
ppm
each.
In
treated
beet
samples,
the
maximum
desmedipham
residues
in/
or
ten
garden
beet
tops
were
0.866
ppm
and
the
residues
from
all
treated
beet
roots
were
<
0.05
ppm
(<
LLMV).
The
data
support
the
proposed
tolerances
for
the
beet
tops
(
1
ppm)
and
beet
roots
(
0.0
5
ppm).

[
Spinach
 
IR
4
received
requests
from
the
states
of
Georgia
and
Delaware
for
the
use
of
desmedipham
on
spinach.
In
support
of
the
requests,
eight
crop
field
trials
were
conducted
in
New
York,
Georgia,
South
Carolina,
Texas,
and
California
that
encompassing
four
NAFTA
Regions.
Residues
of
desmedipham
in/
on
spinach
leaves
were
quantified
using
an
HPLC/
UV
analytical
method
that
was
adequate
for
data
collection
purposes.
The
lowest
level
of
method
validation
(
LLMV)
for
desmedipham
in/
on
spinach
leaves
was
0.05
ppm.
In
treated
samples
of
spinach,
residues
ranged
from
below
0.05
ppm
(<
LLMV)
to
5.0
ppm,
the
highest
residue
level.
The
data
support
the
proposed
6.0
ppm
tolerance
for
spinach.]

B.
Toxicological
Profile
3
1.
Acute
toxicity.
[
Desmedipham
is
of
low
acute
toxicity
placing
the
active
ingredient
in
Toxicity
Category
III
and
IV.
Desmedipham
is
non­
irritating
to
the
skin
and
is
not
a
skin
sensitizer.]

2.
Genotoxicty.
[
Desmedipham
has
been
evaluated
through
a
full
battery
of
mutagenicity
assays.
Desmedipham
was
not
mutagenic
or
genotoxic
in
most
of
the
assays
(
mouse
micronucleus
assay,
in
vitro
human
lymphocytes
assay,
bacterial
reverse
mutation
assay)
in
either
the
presence
or
absence
of
metabolic
activation.]

3.
Reproductive
and
developmental
toxicity.

[
i.
Teratology
­
Rat
Groups
of
24
time
mated
female
rats
received
desmedipham
by
oral
gavage
either
0,
10,
100
or
500
mg/
kg/
day
for
gestation
days
6
through
15.
Maternal
toxicity
was
manifested
as
a
reduction
in
body
weight
gain
during
the
dosing
period.
The
maternal
toxicity
NOEL
is
10
mg/
kg
day
based
on
hematological
findings
(
Heinz
body
formation).
The
developmental
toxicity
NOEL
is
100
mg/
kg/
day
based
on
the
increase
in
fetal
incidence
of
skeletal
anomalies.

ii.
Teratology
­
Rabbit
Desmedipham
was
administered
to
groups
of
16
time­
mated
chinchilla
hybrid
rabbits
by
oral
gavage
from
day
six
to
day
27
of
gestation
at
dose
levels
of
0,
50,
150
and
450
mg/
kg/
day.
The
maternal
toxicity
NOEL
is
150
mg/
kg/
day
based
on
decreased
body
weight
gain.
The
developmental
toxicity
NOEL
is
150
mg/
kg/
day
based
on
increased
incidence
of
skeletal
anomalies
and
reduced
fetal
body
weights.

iii.
Two­
Generation
Reproduction
­
Rat
Desmedipham
was
administered
continuously
at
dietary
concentrations
of
0,
50,
250
and
1250
ppm
(
approximately
0,
4,
20,
or
110
mg/
kg/
day,
respectively)
through
two
successive
generations
of
Wistar
rats.
Parental
animals
(
30
per
sex
and
dose
in
the
F
0
and
26
in
the
F
1
generations)
received
the
test
diets
through
a
pre­
mating
period
of
at
least
80
days,
during
mating,
gestation
and
lactation.
Significant
reductions
in
parental
body
weights
at
the
highdose
level
and
hemolytic
anemia
accompanied
by
significant
increases
in
splenic
weights
and
compensatory
functioning
of
the
thyroid
at
the
mid­
and
high­
dose
levels
were
observed.
The
NOEL
for
parental
systemic
toxicity
is
4
mg/
kg/
day.
No
specific
reproductive
toxicity
was
noted;
however,
developmental
toxicity
was
noted
as
reductions
in
lactational
body
weights
of
pups
at
the
high
dose
level.
The
developmental/
offspring
systemic
toxicity
NOEL
is
20
mg/
kg/
day
and
the
NOEL
for
reproductive
toxicity
is
equal
to
or
greater
than
110
mg/
kg/
day.]

4.
Subchronic
Toxicity
[
i.
90
Day
Dietary
­
Rat
Wistar
rats
(
groups
of
25
males
and
25
females)
were
treated
with
dietary
levels
of
0,
6,
30,
60
and
300
ppm
desmedipham.
Hematology
revealed
slight
increases
in
methemoglobin
values,
minimally
increased
reticulocyte
counts
and
slightly
lower
T4
values
at
300
ppm.
4
The
NOEL
corresponded
to
60
ppm
(
5.6
mg/
kg/
day
for
males
and
5.2
mg/
kg/
day
for
females)
based
on
the
hematological
changes.

ii.
90
Day
Dietary
­
Dog
Groups
of
four
male
and
four
female
Beagle
dogs
received
desmedipham
at
dietary
concentrations
of
0,
1,
5
or
150
ppm
for
90
days.
Methemoglobinemia
was
noted
at
150
ppm
although
no
other
effect
relating
to
the
formation,
function
or
destruction
of
erythrocytes
was
detected.
No
other
treatment­
related
effects
occurred
at
any
dose
level.
NOEL:
5
ppm,
(
0.18
mg/
kg
/
day),
based
on
the
induction
of
methemoglobinemia..

iii.
21
Day
Dermal
Toxicity
­
Rabbit
In
a
21­
day
dermal
toxicity
study,
Betanex
(
16%
desmedipham)
was
applied
to
the
shaved
skin
of
four
groups
of
10
male
and
10
female
rabbits
each
for
6
hours
per
day
for
21
days
at
dosages
of
either
0,
60,
180,
or
540
mg/
kg
body
weight.
The
findings
on
gross
necropsy
and
histopathology
involved
dermal
lesions.
Microscopically,
there
was
a
dose­
related
incidence
of
acanthosis,
hyperkeratosis,
dermal
inflammatory
cell
infiltrates
and
epidermal
ulceration
(
highest
group
only).
The
systemic
toxicity
NOEL
is
60
mg/
kg/
day.]

5.
Chronic
Toxicity
/
Oncogenicity
[
i
Chronic
Toxicity
­
Dog
In
a
12­
month
oral
feeding
study,
desmedipham
was
administered
to
beagle
dogs
for
1
year
at
dietary
levels
of
0,
300,
1500,
and
5000
ppm
(
equal
to
0,
9.6,
52.5,
and
167.7
mg/
kg/
day
for
males
and
0,
10.4,
57.4,
and
200.7
mg/
kg/
day
for
females,
respectively).
For
the
first
28
days,
the
highdose
level
was
7500
ppm
and
this
was
reduced
to
5000
ppm
because
of
weight
loss
and
marked
toxicity.
There
was
a
dose­
related
increase
in
methemoglobin
in
males
and
females
which
was
significant
(
p<
0.01)
in
mid­
and
high­
dose
groups
and
an
increase
in
Heinz
bodies
in
the
high
dose
group.
There
was
a
decrease
in
serum
triiodothyronine
(
T3)
in
dosed
dogs
and
a
decrease
in
thyroxine
(
T4)
in
mid­
and
high­
dose
females.
This
was
accompanied
by
an
increase
in
thyroid
weights.
There
were
increases
in
hematopoiesis
in
the
spleen
in
high­
dose
dogs
and
accompanying
increases
in
spleen
weights.
The
system
toxicity
NOEL
is
less
than
9.6
mg/
kg/
day
for
males
and
less
than
10.4
mg/
kg/
day
for
females.
Based
on
the
results
from
a
special
follow­
up
study
in
dogs
identified
the
threshold
NOEL
to
be
150
ppm
(
equal
to
5.1
and
4.3
mg/
kg/
day
for
males
and
females,
respectively).

ii.
Combined
Chronic
Toxicity/
Oncogenicity
­
Rat
Groups
of
70
male
and
70
female
Wistar
rats
received
dietary
concentrations
of
0,
60,
300
or
1500
ppm
desmedipham
for
two
years.
Treatment
had
no
effect
on
survival,
clinical
signs
or
food
intakes.
From
three
months
onwards,
hematological
investigations
revealed
methemoglobinaemia,
Heinz
body
formation,
slight
changes
in
erythrocyte
count
and
other
erythrocytic
morphology
(
polychromatophilia,
anisocytosis
and
poikilocytosis),
slight
alteration
in
hemoglobin
parameters
and
a
compensatory
erythropoietic
response
at
300
and
1500
ppm.
Histopathology
revealed
a
dose­
related
extramedullary
hemopoiesis
and
hemosiderosis
in
the
spleen
of
all
treated
groups.
In
addition,
an
increase
in
thyroid
follicular
cell
hypertrophy
was
noted
in
all
treated
groups
at
one
year
5
and
at
300
and
1500
ppm
after
two
years.
There
was
no
evidence
of
a
tumorigenic
effect
at
any
dose
level.
NOEL:
60
ppm
(
corresponding
to
3.9
for
males
or
3.2
mg/
kg/
day
for
females,
respectively)
based
on
the
hematological
changes
occurring
at
300
ppm.

iii.
Oncogenicity
­
Mouse
Desmedipham
was
administered
to
groups
of
60
male
and
60
female
NMRI
mice
at
dietary
concentrations
of
0,
30,
150
or
750
ppm
for
two
years.
Body
weight
gain
was
reduced
in
the
high
dose
males.
At
termination,
no
treatment­
related
organ
weight
differences
were
recorded.
Histopathology
revealed
no
evidence
of
treatment­
related
changes.
NOEL:
150
ppm,
corresponding
to
22
and
31
mg/
kg/
day
for
males
and
females,
respectively,
based
on
the
hematological
changes
at
750
ppm.]

6.
Neurotoxicity
Evaluation
[
Desmedipham
has
not
shown
any
evidence
of
neurotoxic
potential
in
any
of
the
toxicity
studies
performed.
Consequently,
no
special
studies
designed
to
investigate
neurotoxicity
have
been
undertaken.]

7.
Animal
Metabolism.
[
Desmedipham,
orally
administered
to
rats,
was
rapidly
and
well
absorbed,
completely
metabolized
and
largely
excreted
within
96
hours.
Furthermore,
tissue
residues
were
generally
low.
The
major
metabolite,
ethyl­
N­
3­
hydroxyphenylcarbamate
is
the
same
in
plants
and
other
animals.]

8.
Metabolite
toxicology.
["
NA­
Remove".]

9.
Endocrine
disruption.
[
There
is
no
evidence
to
suggest
that
desmedipham
has
an
effect
on
any
endocrine
system.]

C.
Aggregate
Exposure
1.
Dietary
exposure.

I.
Food.
Tier
1
dietary
risk
assessments
were
conducted
for
acute
and
chronic
exposures.
Dietary
exposure
estimates
were
based
on
tolerances
that
have
been
established
[
40
CFR
180.353
(
a)
and
(
b)]
for
desmedipham
in
or
on
sugar
beets,
garden
beets
(
under
the
Section
18
emergency
exemptions),
and
the
new
proposed
tolerance
for
spinach
at
6.0
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
in
these
assessments.
Dietary
exposure
estimates
were
calculated
using
the
Dietary
Exposure
Evaluation
Model
software
(
DEEMFCID
 
,
Exponent,
Inc.,
formerly
Novigen
Sciences,
Inc.,
Version
2.02)
and
the
1994­
1996
and
1998
USDA
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII)
consumption
data
base.
An
acute
reference
dose
(
RfD)
of
0.1
mg/
kg/
day
was
used
for
the
acute
dietary
assessment
and
was
based
on
the
results
from
a
developmental
toxicity
study
in
rats
(
NOEL
10
mg/
kg/
day)
and
an
uncertainty
factor
of
100
(
10X
for
interspecies
extrapolation
and
10X
for
6
intraspecies
variation).
The
U.
S.
population
was
estimated
to
have
an
acute
dietary
exposure
of
0.000166
mg/
kg/
day
(
95th
percentile)
which
occupies
0.17%
of
the
acute
RfD.
The
most
highly
exposed
subpopulation
was
non­
nursing
infants
at
0.84%
(
0.0.000840
mg/
kg/
day)
of
the
acute
RfD.
Chronic
dietary
exposure
was
evaluated
using
a
reference
dose
(
RfD)
of
0.04
mg/
kg/
day,
based
on
a
2­
generation
reproduction
study
in
rats
(
NOAEL
of
4.0
mg/
kg/
day)
and
an
uncertainty
factor
of
100
(
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variation).
Chronic
dietary
exposure
for
the
U.
S.
population
was
estimated
to
be
0.000247
mg/
kg/
day
which
occupies
0.6%
of
the
chronic
reference
dose.
The
most
highly
exposed
subpopulation
was
non­
nursing
infants
at
2.8%
(
0.001123
mg/
kg/
day)
of
the
chronic
reference
dose.
There
is
no
concern
for
exposures
occupying
100%
or
less
of
the
RfD.
Therefore,
the
acute
and
chronic
dietary
exposures
for
both
the
U.
S.
population
and
infants
and
children
are
well
within
acceptable
levels.
ii.
Drinking
water.
US
EPA's
Standard
Operating
Procedure
(
SOP)
for
Drinking
Water
Exposure
and
Risk
Assessments
was
used
to
perform
the
drinking
water
assessment.
This
SOP
uses
a
variety
of
tools
to
conduct
drinking
water
assessments.
These
tools
include
water
models
such
as
SCI­
GROW,
FIRST,
PRZMS/
EXAMS,
and
monitoring
data.
When
monitoring
data
is
not
available,
the
models
are
used
to
predict
potential
residues
in
surface
and
ground
water
and
the
highest
value
is
assumed
to
be
the
drinking
water
residue.
In
the
case
of
desmedipham,
SCI­
GROW
and
FIRST
models
were
used
to
estimate
a
water
residue.
The
estimated
concentrations
of
the
pesticide
in
surface
water
or
ground
water
were
calculated
and
then
compared
to
the
drinking
water
level
of
comparison
(
DWLOC)
.
The
DWLOC
is
the
concentration
of
a
pesticide
in
drinking
water
that
would
be
acceptable
as
an
upper
limit.
These
drinking
water
levels
of
comparison
estimates
are
based
on
conservative
dietary
(
food)
exposures
and
are
expected
to
be
much
higher
in
real
world
situations.
For
adults,
the
chronic
DWLOC
was
1,391
ppb
and
the
acute
DWLOC
was
3494
ppb.
The
chronic
and
acute
DWLOCs
for
non­
nursing
infants
were
389
ppb
and
992
ppb,
respectively.
The
estimated
environmental
concentration
(
EEC)
for
the
worst
case
chronic
scenario
was
71
ppb
(
FIRST)
and
the
acute
EEC
(
FIRST)
was
130
ppb.
The
DWLOCs
are
substantially
greater
than
the
high­
end
estimated
exposure
from
the
surface
water
models
indicating
risk
from
potential
drinking
water
exposure
to
desmedipham
is
well
within
acceptable
levels.

2.
Non­
dietary
exposure.

Desmedipham
products
are
not
labeled
for
residential
uses
(
food
or
non­
dietary),
thereby
eliminating
the
potential
for
residential
exposure
or
non­
occupational
exposure.

D.
Cumulative
Effects
[
Desmedipham
(
ethyl
m­
hydroxy­
carbanilate
carbanilate)
is
a
member
of
the
phenyl
carbamate
family
of
herbicides.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
to
desmedipham
and
any
other
substances.

E.
Safety
Determination
7
1.
U.
S.
population
Using
the
conservative
exposure
assumptions
described
above
and
based
on
completeness
of
the
toxicity
data,
it
can
be
concluded
that
aggregate
exposure
to
residues
of
desmedipham
present
a
reasonable
certainty
of
no
harm.
Exposure
from
residues
is
crops
utilize
0.2%
of
the
acute
PAD
and
0.6%
of
the
chronic
PAD.
EPA
generally
has
no
concerns
for
exposures
below
100%
of
the
PAD.
DWLOC
are
well
above
the
estimated
drinking
water
concentrations
as
calculated
by
conservative
models.
There
are
no
residential
uses
so
aggregate
exposure
consists
of
food
and
drinking
water
exposures.
The
conservative
Tier
1
assessments
demonstrate
a
reasonable
certainty
of
no
harm
will
result
from
uses
of
desmedipham
for
the
U.
S.
population.

2.
Infants
and
children.
Using
the
conservative
exposure
assumptions
described
above
and
based
on
completeness
of
the
toxicity
data,
it
can
be
concluded
that
aggregate
exposure
to
residues
of
desmedipham
present
a
reasonable
certainty
of
no
harm.
Exposure
from
residues
is
crops
utilize
0.8%
of
the
acute
PAD
and
2.8%
of
the
chronic
PAD.
EPA
generally
has
no
concerns
for
exposures
below
100%
of
the
PAD.
DWLOC
are
well
above
the
estimated
drinking
water
concentrations
as
calculated
by
conservative
models.
There
are
no
residential
uses
so
aggregate
exposure
consists
of
food
and
drinking
water
exposures.
The
conservative
Tier
1
assessments
demonstrate
a
reasonable
certainty
of
no
harm
will
result
from
uses
of
desmedipham
for
infants
and
children.

F.
International
Tolerances
[
There
is
no
CODEX
Maximum
Residue
Levels
(
MRL)
established
for
desmedipham.
There
is
an
European
Union
(
EU)
MRL
of
0.1
ppm
for
sugar
beet
root
and
a
temporary
EU
MRL
of
0.05
ppm
for
spinach.]