Document ID: EPA-HQ-OPP-2006-0216-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-05-03T04:00Z

1
of
17
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
January
24,
2006
MEMORANDUM:

Subject:
ID#
05OR11
­
Section
18
Exemption
for
the
use
of
Dimethenamid­
P
on
Winter
Squash
in
Oregon.

DP
Barcode:
D314487
Decision
Number:
354475
PC
Code:
129051
Trade
Name:
Outlook
®
Class:
Herbicide
40
CFR:
§
180.464(
a)
and
(
b)
EPA
Reg.
Number:
4969­
156.

From:
Christina
Swartz,
Chemist
Shih­
Chi
Wang,
Biologist
Registration
Action
Branch
2
Health
Effects
Division
(
7509C)

Through:
Michael
Doherty,
Chemist
Registration
Action
Branch
2
Health
Effects
Division
(
7509C)

Through:
Richard
Loranger,
Branch
Senior
Scientist
Registration
Action
Branch
2
Health
Effects
Division
(
7509C)

To:
Andrew
Ertman/
Robert
Forrest,
PM
Team
5
Minor
Use,
Inerts,
and
Emergency
Response
Branch
Registration
Division
(
7505C)
2
of
17
Introduction
The
State
of
Oregon
Department
of
Agriculture
has
requested
an
emergency
exemption
for
the
use
of
dimethenamid­
P
on
winter
squash
grown
in
Oregon
for
control
of
nightshade
(
Solanum
spp.)
and
other
summer
weeds.
The
request
entails
application
of
1,920
lbs
of
the
active
ingredient
(
ai)
to
3,000
acres
of
land
between
April
1,
2005
and
August
1,
2005.

Agency
Memoranda
Used
to
Support
this
Section
18
Exemption
Risk
Assessment
Dimethenamid
/
Dimethenamid­
P.
Human
Health
Risk
Assessment
[
in
support
of
the
TRED].
Memo
dated
8/
12/
2004,
R.
Griffin,
DP
Barcode
No.
D304790.

EFED
Water
Memo:
EFED
Environmental
Risk
Assessment
for
Section
18
emergency
exemption
for
the
use
of
Dimethenamid­
P
(
Outlook
®
Herbicide)
Use
on
"
Golden
Delicious"
winter
squash
grown
in
western
Oregon.
D314488,
J.
Wolf,
4/
18/
05.

Dimethenamid­
P:
Acute
and
Chronic
Dietary
Exposure
Assessment
for
the
Section
18
Emergency
Exemption
Request
for
the
use
on
Winter
Squash
in
Oregon,
C.
Swartz,
1/
24/
06,
DP
Barcode
No.
D316226.

Dimethenamid
and
dimethenamid­
P
are
selective,
pre­
emergence,
chloroacetamide
herbicides
with
existing
tolerances
for
corn,
sorghum,
peanuts,
dry
beans,
and
soybean.
Tolerances
are
established
for
residues
of
dimethenamid,
(
RS)­
2­
chloro­
N­[(
1­
methyl­
2­
methoxy)
ethyl]­
N­(
2,4­
dimethylthien­
3­
yl)
acetamide
under
40
CFR
§
180.464(
a)
and
(
b).
As
the
tolerance
expression
includes
both
the
R
and
S
isomers,
these
tolerances
also
cover
the
registered
uses
of
dimethenamid­
P.
With
the
exception
of
the
time­
limited
tolerances
on
sugar
beet
molasses
and
dried
pulp
at
0.05
ppm,
tolerances
for
all
other
plant
commodities
are
set
at
0.01
ppm,
which
is
the
enforcement
method
limit
of
quantitation
(
LOQ).

In
conjunction
with
the
TRED
completed
in
8/
2004,
HED
recommended
in
favor
of
establishing
tolerances
for
residues
in
dry
bulb
onions,
garlic,
dry
bulb
shallots,
tuberous/
corm
vegetables,
sugar
and
garden
beets,
and
horseradish.

In
target
crops
and
rotational
crops,
parent
dimethenamid
is
the
only
residue
of
concern
for
both
tolerance
enforcement
and
risk
assessment.
Residues
in
livestock
commodities
have
been
classified
under
40
CFR
§
180.6(
a)(
3),
i.
e.,
there
is
no
reasonable
expectation
of
finite
residues;
therefore,
no
tolerances
are
needed
for
livestock
commodities.
In
drinking
water,
parent
dimethenamid
is
the
only
residue
of
concern
for
risk
assessment.

The
most
recent
risk
assessment
for
dimethenamid
was
completed
in
8/
04;
no
new
toxicity
data
have
been
received
since
that
time,
and
there
have
been
no
changes
to
the
toxicological
endpoints
selected
for
risk
assessment.
Therefore,
reference
may
be
made
to
the
8/
04
risk
assessment
for
information
pertaining
to
the
toxicological
and
residue
chemistry
databases.
3
of
17
Proposed
Use
The
submission
from
the
OR
Dept.
of
Agriculture
includes
the
Section
18
use
for
control
of
nightshade
(
Solanum
spp.)
and
other
summer
annual
weeds
on
only
the
"
Golden
Delicious"
variety
of
winter
squash.
The
proposed
maximum
single
season
application
rate
for
winter
squash
is
0.84
lb
a.
i./
acre.
The
product
formulation
is
an
emulsifiable
concentrate
containing
63.9%
ai
dimethenamid­
P.
The
method
of
application
is
ground
broadcast,
after
planting
and
prior
to
emergence
of
the
crop.
The
proposed
label
also
states
that
0.5
inches
of
irrigation
water
must
be
added
after
application
to
incorporated
(
water­
in)
the
herbicide
in
the
soil.
The
proposed
use
does
not
include
aerial
application
or
application
through
irrigation.

The
counties
where
is
product
is
to
be
used
in
this
exemption
include
Benton,
Clackamas,
Douglas,
Jackson,
Josephine,
Lane,
Linn,
Marion,
Polk,
Washington,
and
Yamhill.
The
petitioner
estimates
that
herbicide
will
be
required
to
treat
a
maximum
of
3,000
acres
of
winter
squash.

Toxicology
The
toxicology
database
is
adequate
to
characterize
the
toxicity
of
dimethenamid
and
to
assess
risk.
HED
has
previously
concluded
that
for
the
purpose
of
human
health
risk
assessment,
the
toxicity
database
for
dimethenamid
adequately
addresses
potential
toxicity
of
dimethenamid­
P.
The
LD
50
study
with
[
S]­
dimethenamid­
P
shows
a
category
II
for
acute
oral
toxicity,
but
category
III
for
acute
dermal
and
category
IV
for
inhalation.
It
is
a
mild
eye
and
skin
irritant
and
causes
slight
skin
sensitization.
Pre­
and
post­
natal
studies
showed
no
increased
offspring
susceptibility.
In
the
21­
day
dermal
rabbit
study,
serum
inorganic
phosphorus
decreases
were
noted
in
males
and
females
at
the
mid­
dose
and
male
body
weight
decrement
at
the
top
dose,
but
only
mild
skin
irritation
was
noted.
Chronic
studies
in
the
rat,
mouse
and
dog
with
[
RS]­
dimethenamid
showed
body
weight
decrement
and
food
efficiency
decrement
at
the
lowest
effect
level
and
at
higher
dose
levels
liver
pathology,
stomach
hyperplasia,
and
some
indication
of
kidney
effects.
In
some
of
the
studies
liver
enzymes
and
cholesterol
levels
were
increased
at
doses
resulting
in
liver
pathology.

Peer
Reviews
classified
[
RS]­
dimethenamid
as
a
group
"
C"
(
possible
human
carcinogen),
and
recommended
that
for
human
risk
assessment
the
reference
dose
(
cPAD)
approach
should
be
used.
A
battery
of
mutagenicity
studies
with
[
S]­
dimethenamid­
P
were
universally
negative
for
genetic
mutations
including
unscheduled
DNA
synthesis.

Toxicological
endpoints
and
doses
for
risk
assessment
selected
for
dimethenamid­
P
are
shown
below;
since
the
10X
FQPA
safety
factor
was
removed
for
dimethenamid,
combined
uncertainty
factors
(
UFs)
of
100X
apply
to
all
of
the
exposure
scenarios,
with
the
exception
of
the
short­
term
dermal
and
inhalation
scenarios,
for
which
an
additional
3X
factor
was
retained
to
account
for
the
lack
of
a
maternal
NOAEL
in
the
developmental
rat
study.
For
dermal
assessments,
a
30%
dermal
absorption
factor
was
used,
while
100%
absorption
was
assumed
for
the
inhalation
route:
4
of
17
Exposure
Scenario
Dose
(
NOAEL)
Study/
LOAEL
[
Tox.
Effects]
Acute
Dietary,
Females
13­
49
7.5
mg/
kg/
day
Dev.
Rabbit/
150
mg/
kg/
day
[
abortions/
postimplantation
loss]
Chronic
Dietary
5
mg/
kg/
day
Combined
chronic/
carcinogenic,
rat/
35/
49
mg/
kg/
day
(
M/
F)
[
body
weight
effects;
microscopic
hepatic
lesions]
Short­
term
dermal/
inhal.
25
mg/
kg/
day
Dev.
Rat/
25
mg/
kg/
day
[
maternal
body
weight
decrement]
Intermediate/
long­
term
dermal/
inhal
5
mg/
kg/
day
Combined
chronic/
carcinogenic,
rat/
35/
49
mg/
kg/
day
(
M/
F)
[
body
weight
effects;
microscopic
hepatic
lesions]

Occupational
Exposure
Two
handler
scenarios
were
assessed
in
conjunction
with
the
proposed
use:

C
Mixing/
Loading
Liquids
for
Ground
Applications
C
Applying
Sprays
with
Groundboom
Equipment
The
maximum
application
rate
listed
on
the
proposed
label
provided
by
the
Registration
Division
was
used
for
all
exposure
assessments
(
0.84
lb
ai/
A).
Standard
assumptions
were
used
with
respect
to
the
acres
treated
per
day
(
80),
body
weight
(
60
kg
to
reflect
the
use
of
a
developmental
endpoint
for
short­
term
exposure),
the
number
of
exposure
days
per
year
(
1
to
30
days
for
shortterm
exposure),
and
the
use
of
unit
exposure
values
from
the
Pesticide
Handlers
Exposure
Database
(
PHED).

The
calculated
margins
of
exposure
(
MOEs)
for
the
mixers/
loaders
are
8.2
at
the
baseline
level
and
890
at
the
minimum
PPE
level
(
single
layer
+
gloves).
The
MOE
for
Applicators
is
1,500
at
the
baseline
level.
The
MOEs
of
890
and
1,500
are
above
HED's
level
of
concern
(
MOE
=
300).

Dietary
Exposure
Acute
and
chronic
dietary
(
food
+
water)
exposure
analyses
were
based
on
tolerance
level
residues
and
100%
crop
treated
assumptions
for
food
commodities;
potential
exposure
from
residues
in
water
was
also
considered
(
see
below).
The
general
U.
S.
population
and
all
population
subgroups
had
risk
estimates
that
were
below
HED's
level
of
concern
(
i.
e.,
<
100%
of
the
population
adjusted
dose
(
PAD)).
The
aPAD
value
for
females
13­
49
is
less
than
1%.
For
chronic
exposure,
the
most
highly
exposed
population
subgroup
is
infants
<
1
year
old,
with
a
cPAD
of
approximately
1%.
All
other
population
subgroups
had
lower
chronic
exposure
and
risk.

Drinking
Water
Exposure
Estimates
EFED
provided
estimated
drinking
water
concentrations
(
EDWCs)
for
the
use
of
dimethenamid
on
winter
squash.
Surface
water
estimates
for
acute
and
chronic
dietary
exposure
are
21.78
ppb
and
4.49
ppb,
respectively.
The
ground
water
EDWC
generated
using
SCI­
GROW
was
much
5
of
17
lower,
at
0.24
ppb.
These
estimates
provide
upper­
bound
estimates
of
dimethenamid
concentrations
in
drinking
water
as
a
result
of
the
proposed
Section
18
use
on
winter
squash.
However,
since
the
EDWCs
incorporated
into
the
risk
assessment
completed
for
reregistration
are
higher,
they
were
used
in
this
assessment,
instead
of
those
generated
for
just
winter
squash.

For
acute
dietary
exposure
assessment,
the
surface
water
residue
estimate
of
49
ppb
was
used;
for
chronic
dietary
assessment,
the
surface
water
EDWC
of
7.9
ppb
was
used.
The
ground
water
estimate
based
on
existing
uses
is
0.42
ppb,
but
it
is
still
significantly
lower
than
surface
water
residues;
therefore,
surface
water
residue
estimates
were
incorporated
directly
into
the
DEEMFCID
 
analysis.

Non­
Dietary,
Non­
Occupational
Exposure
There
are
no
non­
agricultural
(
or
residential)
uses
of
dimethenamid.
Therefore,
no
non­
dietary
residential
exposures
are
expected.

Aggregate
Risk
Since
there
are
no
residential
uses
of
dimethenamid,
and
since
acute
and
chronic
water
residues
were
incorporated
into
the
dietary
exposure
analyses,
the
reported
acute
and
chronic
dietary
exposures
are
aggregate
food
+
water
risks
associated
with
the
proposed
Section
18
use
and
the
existing
registered
uses.

Cumulative
Risk
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
dimethenamid
and
any
other
substances.
Also,
dimethenamid
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
Section
18
tolerance
action,
therefore,
EPA
has
not
assumed
that
dimethenamid
has
a
common
mechanism
of
toxicity
with
other
substances.

Tolerance
Harmonization
There
are
no
CODEX
or
Canadian
maximum
residue
limits
(
MRLs)
established
for
dimethenamid
or
dimethenamid­
P.
Therefore,
tolerance
harmonization
is
not
germane
to
the
current
Section
18
proposed
use.

Conclusions
For
the
proposed
use
of
dimethenamid­
P
on
winter
squash
in
Oregon,
aggregate
(
food
+
water)
risk
estimates
are
below
HED's
level
of
concern.
The
estimated
occupational
exposures
are
below
HED's
level
of
concern.
HED
has
no
concerns
that
would
preclude
the
establishment
of
a
time­
limited
tolerance
for
this
Section
18
exemption
of
0.1
ppm
for
residues
of
dimethenamid­
P
in/
on
winter
squash.
6
of
17
Toxicological
Considerations
The
acute
oral
toxicity
LD50
study
with
[
S]­
dimethenamid­
P
shows
a
category
II.
It
is
category
III
for
acute
dermal
and
inhalation,
is
a
mild
eye
and
skin
irritant,
and
causes
slight
skin
sensitization.
The
acute
oral
toxicity
LD50
with
[
RS]­
dimethenamid
is
category
III
and
the
remaining
categories
are
the
same
as
[
S]­
Dimethenamid­
P.

Pre­
and
post­
natal
studies
showed
no
increased
offspring
susceptibility.
The
developmental
toxicity
studies
show
increased
post­
implantation
loss
and
minor
skeletal
variations
in
the
rat
and
late
resorptions
and
minor
skeletal
variations
in
the
rabbit
at
the
highest
dose
tested,
but
no
increased
quantitative
sensitivity
in
the
conceptus.
In
the
rabbit,
the
developmental
effects
occurred
at
the
same
dose
as
maternal
toxicity
whereas
in
the
rat,
the
developmental
toxicity
occurred
at
much
higher
doses
than
in
the
mothers.
The
reproduction
study
showed
pup
weight
decrements
and
parental
weight
decrements
at
the
same
dose
levels.
The
only
other
effects
noted
were
liver
weight
increases
in
both
parental
sexes.

In
the
21­
day
dermal
rabbit
study,
serum
inorganic
phosphorus
decreases
were
noted
in
males
and
females
at
the
mid­
dose
and
male
body
weight
decrement
at
the
top
dose,
but
only
mild
skin
irritation
was
noted.
Chronic
studies
in
the
rat,
mouse
and
dog
with
[
RS]­
dimethenamid
showed
body
weight
decrement
and
food
efficiency
decrement
at
the
lowest
effect
level
and
at
higher
dose
levels
liver
pathology,
stomach
hyperplasia,
and
some
indication
of
(
unconfirmed)
kidney
effects.
In
some
of
the
studies
liver
enzymes
and
cholesterol
levels
were
increased
at
doses
resulting
in
liver
pathology.
Longer
studies
show
toxicity
at
lower
doses.
The
rat
was
the
most
sensitive
species
to
the
toxic
effects
of
[
RS]­
dimethenamid.

Peer
Reviews
classified
[
RS]­
dimethenamid
as
a
group
"
C"(
possible
human
carcinogen),
and
recommended
that
for
human
risk
assessment
the
reference
dose
(
cPAD)
approach
should
be
used.
An
increasing
trend
for
liver
adenomas
was
seen
in
males
in
the
rat
chronic
study.
No
dose­
related
tumors
were
seen
in
the
mouse
carcinogenicity
study.

A
battery
of
mutagenicity
studies
with
[
S]­
dimethenamid­
P
were
universally
negative
for
genetic
mutations
including
unscheduled
DNA
synthesis.
However,
mutagenicity
studies
with
[
RS]­
dimethenamid
showed
positive
results
for
unscheduled
DNA
synthesis
and
there
were
equivocal
results
in
two
dominant
lethal
studies.

The
toxicity
data
base
for
the
[
RS]
mixture
is
complete
and
the
bridging
studies
to
the
[
RS]­
dimethenamid
toxicity
data
are
complete;
these
bridging
studies
consist
of
the
6
acute
studies,
a
subchronic
study
in
rats,
a
developmental
toxicity
study
in
rats
and
a
battery
of
mutagenicity
studies.
There
are
minor
inconsistencies
between
the
two
sets
of
data.
In
the
developmental
toxicity
studies
in
the
rat
with
[
S]­
dimethenamid­
P,
maternal
weight
decrement
was
shown
at
1/
8
the
LOAEL
for
mothers
dosed
with
[
RS]­
dimethenamid.
Since
the
toxicity
in
90­
day
feeding
studies
in
rats
with
[
S]­
dimethenamid­
P
and
[
RS]­
dimethenamid
were
very
similar,
the
finding
of
increased
toxicity
in
pregnant
dams
may
suggest
that
[
S]­
dimethenamid­
P
is
more
toxic
to
pregnant
rats.
This
difference
in
doses
resulting
in
body
weight
decrement
may
be
due
to
strain
drift
in
the
Sprague
Dawley
rats
used,
since
the
studies
were
conducted
9
years
apart.
7
of
17
Metabolism
studies
with
[
RS]­
dimethenamid
showed
extensive
metabolism
(>
30
metabolites).
Thirty­
one
metabolites
were
identified
and
quantified.
The
initial
metabolite
formed
was
the
glutathione
conjugate
of
the
parent
at
the
active
chlorine
"
to
the
carbonyl
group,
with
subsequent
metabolism
at
the
glutathione
residue.
The
parent
was
extensively
metabolized,
being
essentially
complete
within
3
days
and
over
90%
being
excreted
in
the
urine,
feces
and
bile
within
7
days.
No
significant
differences
in
metabolism/
excretion
were
seen
between
males
and
females
including
biliary
excretion.
Up
to
45
putative
metabolites
were
reported
in
the
urine
and
up
to
50
were
reported
in
the
feces.
Of
the
unidentified
metabolites
none
exceeded
3
%
and
most
were
less
than
1%
of
the
administered
dose.
Saturation
of
the
metabolic
system
was
seen
at
the
1,000
mg/
kg
dose.

The
[
RS]­
dimethenamid
and
[
S]­
dimethenamid­
P
show
similar
toxicity.
Both
products
show
similar
toxicity
and
endpoints
in
the
90­
day
subchronic
studies,
the
acute
studies
and
the
mutagenicity
studies.
Both
products
are
likely
to
be
extensively
metabolized
to
the
similar
quantifiable
metabolites
(
about
30)
and
to
the
approximately
70
metabolites
too
low
to
be
quantified.
The
initial
reaction
in
the
rat
is
conjugation
with
glutathione
with
most
subsequent
metabolic
modification
occurring
at
the
glutathione
conjugate.
The
glutathione
conjugation
does
not
involve
the
asymmetric
[
RS]­
carbon
of
the
pesticide
structure,
and
thus
there
is
good
reason
to
expect
similar
toxicities
for
both
products.

However,
[
S]­
dimethenamid­
P
apparently
showed
slight
maternal
weight
gain
decrement
at
a
lower
dose
than
[
RS]­
dimethenamid
in
developmental
toxicity
studies
in
the
rat.
This
may
suggest
that
[
S]­
dimethenamid­
P
is
more
toxic
to
the
pregnant
rat.
This
apparent
difference
in
toxicity
of
the
two
products
is
difficult
to
compare
because
the
two
studies
were
conducted
9
years
apart
and
the
dose
selection
in
the
two
developmental
studies
with
the
two
products
were
different.
In
addition,
a
range­
finding
study
conducted
with
[
S]­
dimethenamid­
P
showed
maternal
body
weight
decrement
comparable
with
the
dose
found
for
the
[
RS]
product,
suggesting
that
the
slight
maternal
body
weight
gain
decrement
at
the
lowest
dose
tested
in
the
definitive
study
could
be
incidental.

It
should
be
noted
that
the
slight
body
weight
gain
decrement
with
an
extra
uncertainty
factor
(
in
addition
to
the
usual
uncertainty
factor
of
100x)
was
selected
as
an
endpoint
in
the
risk
assessment
to
protect
the
potentially
pregnant
female.
8
of
17
Table
1.
Summary
of
Toxicological
Dose
and
Endpoints
for
[
S]­
DIMETHENAMID­
P.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
Females
13­
49
years)

Based
on
[
RS]
data
NOAEL
=
75
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.75
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
0.75
mg/
kg/
day
Developmental
Toxicity
in
rabbits
Maternal;
LOAEL
=
150
mg/
kg/
day
based
on
abortions
and
decreased
body
weight
gain
and
food
consumption.
Developmental;
LOAEL
=
150
mg/
kg/
day
based
on
postimplantation
loss
Acute
Dietary
(
General
US
Pop.)
Not
Applicable
No
studies
identify
an
acute
hazard
(
dose
and
endpoint)
based
on
a
single
oral
exposure
(
dose).

Chronic
Dietary
(
All
populations)

Based
on
[
RS]
data
NOAEL=
5
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.05
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.05
mg/
kg/
day
Chronic/
carcinogenicity
rats
LOAEL
=
M/
F;
36/
49
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain
in
both
sexes,
increased
food
conversion
ratios
in
females,
and
increased
microscopic
hepatic
lesions
in
both
sexes.

Dermal
Absorption
Based
on
[
RS]
data
30%
No
studies
are
available.
Value
estimated
from
the
ratio
of
the
LOAEL
for
maternal
weight
decrement
in
developmental
study
to
LOAEL
for
male
weight
decrement
in
the
21­
day
dermal
study.

Ratio
of
[(
Developmental
rabbit
maternal
LOAEL,
body
weight)/(
21­
day
Dermal
rabbit
LOAEL
for
systemic
toxicity,
body
weight)]
X
100
=
(
150/
500)
x
100
=
30%

Short­
Term
Dermal
(
1
to
30
days)

Based
on
[
S]
data
Oral
LOAEL=
25
mg/
kg/
day
a
DA
=
30%
Occupational
=
LOC
for
MOE
=
300
Developmental
Tox.
Study
in
rats
LOAEL
=
25
mg/
kg/
day
based
on
maternal
body
weight
decrement.

Intermediate
&
Long­
Term
Dermal
(
1­
6
months
&
1
to
>
6
months)
b
Based
on
[
RS]
data
Oral
NOAEL
=
5
mg/
kg/
day
Dermal
absorption
=
30%
Occupational
LOC
for
MOE
=
100
Chronic
study
in
rats
LOAEL
=
M/
F;
36/
49
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain
in
both
sexes,
increased
food
conversion
ratios
in
females,
and
increased
microscopic
hepatic
lesions
in
both
sexes.
Table
1.
Summary
of
Toxicological
Dose
and
Endpoints
for
[
S]­
DIMETHENAMID­
P.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
9
of
17
Short­
Term
Inhalation
(
1
to
30
days)

Based
on
[
S]
data
Oral
study
LOAEL=
25
mg/
kg/
day
a
Assume
100%
absorption
Occupational
LOC
for
MOE
=
300
Developmental
tox.
study
in
rats
LOAEL
=
25
mg/
kg/
day
based
on
maternal
body
weight
decrement
Intermediate
&
Long­
Term
Inhalation
(
1­
6
months
&
1
to
>
6
months)
b
Based
on
[
RS]
data
Oral
NOAEL
=
5
mg/
kg/
day
Assume
100%
absorption
Occupational
LOC
for
MOE
=
100
Chronic
study
in
rats
LOAEL
=
M/
F;
36/
49
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain
in
both
sexes,
increased
food
conversion
ratios
in
females,
and
increased
microscopic
hepatic
lesions
in
both
sexes.

Carcinogenicity
Based
on
[
RS]
data
"
C"
Possible
human
carcinogen.
(
No
Q1*)

a
An
extra
UF
of
3X
was
used
to
account
for
no
NOAEL.
b
Although
this
chronic
rat
study
is
a
long
term
study,
it
shows
a
body
weight
decrement
at
10
weeks
in
rats
with
[
RS]­
dimethenamid
with
a
NOAEL/
LOAEL
of
M/
F:
(
5/
6.8)/(
36/
49)
mg/
kg/
day
and
thus
is
appropriate
for
the
intermediate
and
long
term
endpoint.
[
RS]
data
and
[
S]
data
mean
that
the
study
was
conducted
with
respectively
[
RS]­
dimethenamid
and
[
S]­
dimethenamid­
P.
UF
=
uncertainty
factor,
FQPA
SF
=
Special
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,
NA
=
Not
Applicable
Occupational
Exposure
Considerations
Product
Use
information/
Application
Timing
The
proposed
Section
18
use
pattern
for
dimethenamid­
P
is
summarized
in
Table
2.

Table
2.
Proposed
Use
Patterns
Crop
Product,
Formulation
Treatment
Type
Applications
Per
Season
1
Maximum
Application
Rate2
(
lb
ai/
acre)
PHI3
(
days)
Per
Application
Per
Season
Winter
Squash
Outlook,
liquid
ground
only
1
0.84
0.84
90
1
Maximum
number
of
applications
allowed
on
label.
2
Rate
=
Maximum
application
rates
specified
on
proposed
labels.
3
PHI
=
Pre­
harvest
Interval
10
of
17
Occupational
Handler
Exposure
and
Risk
Equations/
Calculations
The
following
equations
were
used
to
calculate
handler
exposure
and
risk:

Dermal
Dose
(
mg/
kg/
day)
=
Rate
(
lb
ai/
A)
x
UE
(
mg/
lb
ai)
x
DA
x
Acres
Treated
(
A/
day)
BW
(
kg)

Inhalation
Dose
(
mg/
kg/
day)
=
Rate
(
lb
ai/
acre)
x
UE
(
mg/
lb
ai)
x
Acres
Treated
(
A/
day)
BW
(
kg)

Where:
Rate
(
Application
Rate)
=
Maximum
application
rate
on
product
label
(
lb
ai/
acre)
UE
(
Unit
Exposure)
=
Exposure
value
derived
from
August
1998
PHED
Surrogate
Exposure
Table
(
mg/
lb
ai
handled)
DA
(
dermal
absorption
factor)
=
Factor
to
account
for
dermal
absorption
(
30%)
when
endpoint
is
selected
from
an
oral
study.
Acres
Treated
=
Maximum
number
of
acres
treated
per
day
(
acres/
day)
BW
=
Body
weight
(
kg)

Combined
Daily
Dose
(
mg/
kg/
day)
=
Dermal
Dose
(
mg/
kg/
day)+
Inhalation
Dose
(
mg/
kg/
day)

Short­
term
MOE
=
NOAEL
(
8
mg/
kg/
day)
Combined
Daily
Dose
(
mg/
kg/
day)

Intermediate­
term
MOE
=
NOAEL
(
6.8
mg/
kg/
day)
Combined
Daily
Dose
(
mg/
kg/
day)

Exposure
Scenarios
There
are
two
handler
scenarios
that
are
expected
to
result
in
the
highest
exposure
for
the
proposed
use:

C
Mixing/
Loading
Liquids
for
Ground
Applications
(
Scenario
1)

C
Applying
Sprays
with
Groundboom
Equipment
(
Scenario
2)

Application
Rate
The
maximum
application
rates
listed
on
the
proposed
labels
provided
by
the
Registration
Division
were
used
for
all
exposure
assessments.
The
maximum
rate
is
0.84
lb
ai/
A.

Area
Treated
Based
on
HED's
Exposure
Science
Advisory
Council
Policy
Number
9.1,
80
acres
per
day
11
of
17
treated
was
assumed
for
application
using
groundboom
equipment.

Body
Weight
The
female
body
weight
(
60
kg)
was
used
for
both
short­
term
and
intermediate­
term
assessments
because
short­
term
endpoints
were
determined
from
a
developmental
study
and
the
female
NOAEL
(
6.8
mg/
kg/
day)
was
used
in
the
intermediate­
term
MOE
calculations
to
represent
the
worst
case.

Exposure
Frequency
No
data
on
the
number
of
exposure
days
per
year
was
provided.
For
this
risk
assessment,
it
was
assumed
that
handlers
would
be
exposed
for
less
than
30
days
per
year
(
i.
e.
short­
term
in
duration).

Unit
Exposures
In
the
absence
of
chemical­
specific
exposure
data
for
assessing
occupational
handler
exposure
and
risk,
the
unit
exposures
used
in
this
assessments
are
based
on
the
PHED
Version
1.1
as
presented
in
the
August
1998
PHED
Surrogate
Exposure
Guide.
PHED
was
designed
by
a
task
force
of
representatives
from
the
U.
S.
EPA,
Health
Canada,
the
California
Department
of
Pesticide
Regulation,
and
member
companies
of
the
American
Crop
Protection
Association.
PHED
is
a
software
system
consisting
of
two
parts 
a
database
of
measured
exposure
values
for
workers
involved
in
the
handling
of
pesticides
under
actual
field
conditions
and
a
set
of
computer
algorithms
used
to
subset
and
statistically
summarize
the
selected
data.
Currently,
the
database
contains
values
for
over
1,700
monitored
individuals
(
i.
e.,
replicates).

Handlers'
Exposure
and
Risk
The
margins
of
exposure
(
MOEs)
for
the
mixers/
loaders
are
8.2
at
the
baseline
(
single
layer)
clothing
level
and
890
at
the
minimum
PPE
level
(
single
layer
clothing
+
gloves).
The
MOE
for
Applicators
is
1,500
at
the
baseline
level.
The
MOEs
of
890
and
1,500
are
above
the
HED's
level
of
concern
(
MOE
=
300).

Assumptions
and
calculations
of
the
risks
for
handlers
are
presented
in
Table
3.

Post­
application
Exposure
and
Risk
Dimethenamid­
P
formulated
as
Outlook
®
is
a
pre­
emergence
herbicide
and
is
applied
to
the
soil.
An
occupational
post­
application
exposure
and
risk
assessment
was
not
performed
because
exposure
to
dimethenamid­
P
for
workers
performing
post­
application
activities
is
expected
to
be
negligible.

The
technical
material
has
a
Category
III
for
acute
dermal
toxicity/
acute
eye
irritation,
and
a
12
of
17
Category
IV
for
acute
dermal
irritation.
Per
the
Worker
Protection
Standard
(
WPS),
a
12­
hr
restricted
entry
interval
(
REI)
is
required.
Therefore,
the
12
hour
REI
appearing
on
the
label
is
appropriate
for
this
chemical.
13
of
17
Table
3.
Non­
Cancer
Risk
for
Handlers.

Exposure
Scenario
(
Scenario
#)
Mitigation
Levela
Dermal
Unit
Exposureb
(
mg/
lb
ai)
Inhalation
Unit
Exposurec
(
Ug/
lb
ai)
Application
Rate
(
lb
ai/
A)
Amount
Treatedd
(
A/
day)
Daily
Dermal
Dosee
(
mg/
kg/
day)
Daily
Inhalation
Dosef
(
mg/
kg/
day)
Combined
Daily
Doseg
(
mg/
kg/
day)
Short­

Term
MOEi
Mixer/
Loader
Liquids
for
Ground
application
(
1)
Baseline
2.9
1.2
0.84
80
0.9744
0.0013
0.9757
8
PPE
0.023
1.2
0.84
80
0.0077
0.0013
0.0090
890
Applicator
Sprays
with
Groundboom
(
3)
Baseline
0.014
0.74
0.84
80
0.0047
0.00083
0.0055
1,500
a
Baseline
consists
of
long­
sleeve
shirt,
long
pants,
shoes,
and
socks
and
no
respirator.
Min.
PPE
consists
of
long­
sleeve
shirt,
long
pants,
shoes,
socks,
chemical­
resistant
gloves,
and
no
respirator.
Max.
PPE
consists
of
coveralls,
chemical­
resistant
gloves,
and
no
respirator.
Eng.
Cont.
consists
of
closed
mixing/
loading
or
enclosed
cockpit.

b
Baseline
Dermal
Unit
Exposure
represents
long
pants,
long
sleeved
shirt,
no
gloves,
open
mixing/
loading,
and
open
cab
tractors,
as
appropriate.
Min.
PPE
Dermal
Unit
Exposure
represents
long
pants,
long
sleeved
shirt,
chemical­
resistant
gloves,
open
mixing/
loading,
and
open
cab
tractors,
as
appropriate.
Max.
PPE
Dermal
Unit
Exposure
represents
coveralls,
chemical­
resistant
gloves,
open
mixing/
loading,
and
open
cab
tractors,
as
appropriate.
Eng.
Cont.
Dermal
Unit
Exposure
represents
closed
mixing/
loading,
and
open
cab
tractors
or
enclosed
cockpit,
as
appropriate.

c
Baseline
Inhalation
Exposure
represents
no
respiratory
protection,
open
mixing/
loading,
and
open
cab
tractors,
as
appropriate.
Eng.
Cont.
Inhalation
Unit
Exposure
represents
closed
mixing/
loading,
and
open
cab
tractors
or
enclosed
cockpit,
as
appropriate.

d
Daily
acres
treated
values
are
from
EPA
estimates
of
acreage
that
could
be
treated
in
a
single
day
for
each
exposure
scenario
of
concern.

e
Daily
dermal
dose
(
mg/
kg/
d)
=
[
unit
dermal
exposure
(
mg/
lb
ai)
*
dermal
absorption
(
0.3)
*
application
rate
(
lb
ai/
acre)
*
daily
acres
treated
/
body
weight
(
60
kg).

f
Daily
inhalation
dose
(
mg/
kg/
d)
=
(
unit
exposure
(
µ
g/
lb
ai)
*
(
1mg/
1000
µ
g)
conversion
*
appl.
rate
(
lb
ai/
acre)
*
daily
acres
treated
/
body
weight
(
60
kg).

g
Combined
daily
dose
=
daily
dermal
dose
+
daily
inhalation
dose.

h
Short­
term
MOE
=
NOAEL
(
8
mg/
kg/
d)
/
combined
daily
dose.
UF
=
300.

i
Intermediate­
term
MOE
=
NOAEL
(
6.8
mg/
kg/
d)
/
combined
daily
dose.
UF
=
100.
14
of
17
Residue
Chemistry
Considerations
Nature
of
the
Residue
The
nature
of
the
residue
in
plants
is
adequately
understood.
Soybean
and
corn
metabolism
studies
are
available
and
have
been
reviewed
by
the
HED
Metabolism
Committee.
The
metabolism
of
dimethenamid
in
plants
involves
conjugation
with
glutathione,
with
subsequent
transformation
of
the
glutathione
moiety
to
yield
a
variety
of
metabolites.
The
residue
of
concern
for
purposes
of
the
tolerance
expression
(
and
risk
assessment)
was
determined
to
be
dimethenamid
per
se.

In
addition,
a
sugar
beet
metabolism
study
was
reviewed
for
use
of
dimethenamid­
P
on
various
root,
tuber,
corm
and
bulb
vegetables.
The
metabolite
profile
was
similar
for
roots
and
tops,
and
dimethenamid
was
not
detected
in/
on
either
commodity.
For
both
roots
and
tops,
the
majority
of
14C­
residues
were
characterized
as
minor
unknowns
each
present
at
#
8%
of
the
TRR.
One
unknown
polar
fraction
accounted
for
>
10%
of
the
TRR
in
roots,
but
was
present
at
<
0.01
ppm.
The
metabolic
pathway
for
[
14C]
dimethenamid
in
sugar
beets
is
complex,
but
proceeds
via
a
pathway
similar
to
that
observed
in
corn
and
soybeans.
However,
two
metabolites
not
identified
in
corn
or
in
soybean
were
found
in
sugar
beets.
These
are
the
sulfoxide
of
the
cysteine
conjugate
and
the
N­
malonyl
conjugate
of
the
cysteine
conjugate,
and
together
accounted
for
<
6
%
of
the
TRR
in
sugar
beets.

After
considering
the
extensive
metabolism
of
dimethenamid
in
animals,
the
exaggerated
dosing
levels
used
in
the
animal
metabolism
studies,
and
the
expected
low
level
of
dietary
exposure
of
livestock
to
dimethenamid,
the
HED
Metabolism
Assessment
Review
Committee
(
MARC)
concluded
that
tolerances
(
and
risk
assessment)
are
not
required
for
animal
commodities.

Analytical
Methods
An
adequate
enforcement
method
is
available
for
determining
dimethenamid
residues
in
plants
and
soil.
The
GC/
NPD
method
(
AM­
0884­
0193­
1)
has
been
validated
by
the
Agency
and
submitted
for
publication
in
FDA's
Pesticide
Analytical
Manual,
Volume
II..
The
method
does
not
separate
the
R
and
S
isomers
of
dimethenamid
and
the
limit
of
quantitation
(
LOQ)
is
0.01
ppm.

As
tolerances
are
not
required
for
animal
commodities,
no
analytical
methods
for
animal
commodities
are
required.

Magnitude
of
the
Residue
To
support
the
Section
18
Emergency
Exemption,
the
IR­
4
submitted
to
the
Oregon
Department
of
Agriculture
the
results
of
field
trials
conducted
in
OR
(
2)
and
WA
(
1)
in
2002,
in
conjunction
with
proposed
Section
3
use
on
winter
squash.
The
study
contained
the
results
of
field
trials
conducted
with
one
pre­
emergence
broadcast
application
at
0.98
lb
ai/
A
(
1.2X).
Residues
were
determined
using
the
enforcement
method,
and
were
all
less
than
0.01
ppm,
the
method
LOQ.
Relevant
field
trial
information
is
summarized
in
Table
4.
15
of
17
Table
4.
Summary
of
Residue
Chemistry
Considerations.

Parameter
Proposed
Use
Residue
Data
Chemical
Dimethenamid­
P
Dimethenamid­
P
Formulation
Outlook
®
Outlook
®

Crop
Winter
squash
Winter
squash
Type
of
Application
ground,
broadcast
ground,
broadcast
Number
of
Applications
1
1
Timing/
Retreatment
Interval
n/
a
n/
a
Individual
Application
Rate
0.84
lb
ai/
A
0.98
lb
ai/
A
Seasonal
Application
Rate
0.84
lb
ai/
A
0.98
lb
ai/
A
Pre­
harvest
Interval
not
specified
108­
131
days
Maximum
Residue
N/
A
All
<
0.01
ppm
Restrictions
0­
Day
PHI;
14­
day
plantback
interval
(
except
crops
listed
on
label).
N/
A
Residue
Data
Source
N/
A
IR­
4
Performing
Laboratory
N/
A
IR­
4
Processed
Food
and
Feed
There
are
no
relevant
processed
commodities
associated
with
the
Section
18
use
on
winter
squash.

Meat,
Milk,
Poultry,
and
Eggs
No
data
have
been
required
for
residues
in
meat,
milk,
poultry
and
eggs,
based
on
the
finding
that
residues
in
these
commodities
may
be
classified
under
Category
3
of
40
CFR
§
180.6(
a),
i.
e.,
there
is
no
reasonable
expectation
of
finite
residues.

Rotational
Crop
Restrictions
Adequate
confined
rotational
crop
data
were
submitted
and
reviewed
in
conjunction
with
reregistration.
The
study
included
data
on
winter
wheat
planted
141
days
after
treatment
(
DAT),
lettuce
planted
322
DAT
and
carrots
planted
332
DAT.
The
maximum
concentration
of
any
metabolite/
degradate
in
harvested
wheat
was
0.01
ppm
for
the
sulfoxide
of
thiolactic
acid
conjugate.
Based
on
these
data,
HED
concluded
that
a
4­
month
rotational
interval
is
adequate
for
fall­
seeded
cereal
grains
and
other
crops
may
be
planted
the
following
Spring.
The
current
use
directions
specify
that
treated
areas
may
be
replanted
at
any
time
with
crops
which
have
dimethenamid
tolerances.

Dietary
Exposure
Analysis
16
of
17
Acute
and
chronic
dietary
exposure
analyses
was
performed
for
dimethenamid­
P
(
Memo,
D316141,
C.
Swartz,
1/
24/
06).
The
dietary
analyses
are
conservative,
based
on
tolerance­
level
residues
and
100%
crop
treated
assumptions
for
all
commodities.
In
addition,
high­
end
modeled
drinking
water
residues
were
incorporated
into
the
dietary
exposure
assessments.
Results
of
these
analyses
are
summarized
in
Table
5.

Table
5.
Summary
of
Dietary
Exposure
and
Risk
for
Dimethenamid­
P.

Population
Subgroup
Acute
(
Food
+
Water)
Chronic
(
Food
+
Water)
Cancer
Analysis
95th
Percentile
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
N/
A
N/
A
0.000205
0.4
Not
Applicable:
No
cancer
risk
assessment
is
required
All
Infants
(<
1
year
old)
0.000605
1.2
Children
1­
2
years
old
0.000329
0.7
Children
3­
5
years
old
0.000315
0.6
Children
6­
12
years
old
0.000221
0.4
Youth
13­
19
years
old
0.000163
0.3
Adults
20­
49
years
old
0.000187
0.4
Adults
50+
years
old
0.000189
0.4
Females
13­
49
years
old
0.002416
0.32
0.000185
0.4
Drinking
Water
Considerations
Estimated
drinking
water
concentrations
(
EDWCs)
for
the
proposed
Section
18
use
on
winter
squash
were
provided
by
the
Environmental
Fate
and
Effects
Division
(
EFED,
memo,
J.
Wolf,
D314488,
4/
18/
2005).
Modeled
drinking
water
concentrations
were
generated
using
PRZM/
EXAMS
assuming
the
maximum
proposed
pre­
emergence
application
rate
of
0.84
lb
a.
i./
acre
for
winter
squash
grown
in
selected
counties
in
Oregon.
Surface
water
EDWCs
were
adjusted
for
percent
crop
area
by
multiplying
by
the
default
factor
of
0.87,
as
dictated
by
EFED
policy.
Surface
water
estimates
for
acute
and
chronic
dietary
exposure
are
21.78
ppb
and
4.49
ppb,
respectively.
The
ground
water
EDWC
generated
using
SCI­
GROW
was
much
lower,
at
0.24
ppb.
These
estimates
provide
upper­
bound
estimates
of
dimethenamid
concentrations
in
drinking
water
as
a
result
of
the
proposed
Section
18
use
on
winter
squash.
However,
since
the
EDWCs
incorporated
into
the
risk
assessment
completed
for
reregistration
are
higher,
they
were
used
in
this
assessment,
instead
of
those
generated
for
just
winter
squash.

For
acute
dietary
exposure
assessment,
the
surface
water
residue
estimate
of
49
ppb
was
used;
for
chronic
dietary
assessment,
the
surface
water
EDWC
of
7.9
ppb
was
used.
The
ground
water
estimate
based
on
existing
uses
is
0.42
ppb,
but
it
is
still
significantly
lower
than
surface
water
residues;
therefore,
surface
water
residue
estimates
were
incorporated
directly
into
the
DEEMFCID
 
analysis.
17
of
17
Aggregate
Risk
Since
there
are
no
residential
uses
of
dimethenamid,
and
since
acute
and
chronic
water
residues
were
incorporated
into
the
dietary
exposure
analyses,
the
reported
acute
and
chronic
dietary
exposures
are
aggregate
food
+
water
risks
associated
with
the
proposed
Section
18
use
and
the
existing
registered
uses.