MEMORANDUM
10­
August­
2001
SUBJECT:
Diuron.
Results
of
the
Health
Effects
Division
(
HED)
Metabolism
Assessment
Review
Committee
(
MARC)
Meeting
Held
on
03­
JULY­
2001.

Reregistration
Case
No.:
0046
PC
Code:
035505
DP
Barcode
No.:
D275688
FROM:
John
S.
Punzi,
Ph.
D.,
Chemist
Reregistration
Branch
II
Health
Effects
Division
[
7509C]

THROUGH:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
[
7509C]

Christine
Olinger,
MARC
Chair
Health
Effects
Division
[
7509C]

TO:
Yan
W.
Donovan,
MARC
Executive
Secretary
Health
Effects
Division
[
7509C]

1.
Attendance
MARC
Members:

Alberto
Protzel,
Richard
Loranger,
Yan
Donovan,
Sheila
Piper,
Abdallah
Khasawinah,
Christine
Olinger,
David
Nixon.

Non
members
attended:

Rich
Griffin,
Ibrahim
Abdel­
Saheb,
James
Jim
Breithaupt,
Sherrie
Kinard,
Carol
Christensen,
Diana
Locke,
John
Punzi.
2
MARC
Members
Absent:

William
Wassell.

MARC
Members
Absent
but
providing
comments:

John
Doherty
2.
Summary
of
Deliberations
The
metabolism
of
diuron
in
plants
and
animals
from
results
of
wheat,
corn,
orange,
ruminant,
and
poultry
studies
together
with
the
environmental
fate
studies
conducted
for
diuron
was
presented
to
the
HED
MARC
on
03/
July/
2001.

The
14C­
containing
residues
that
were
identified
in
oranges
were:
diuron,
3,4­
dichlorophenylurea
(
DCPU),
and
3­(
3,4­
dichlorophenyl)­
1­
methylurea
(
DCPMU)
(
Figure
1).
These
compounds
were
detected
only
in
trace
quantities
(<
0.01­
0.03
ppm)
in
pulp
and
peels.
No
other
dichloroanilinecontaining
metabolites
were
identified.
The
majority
of
radioactivity
in
the
aqueous/
organic
fractions
was
characterized
as
polar
unknowns.

The
14C­
containing
residues
that
were
identified
in
corn
plants
were:
Following
postemergence
treatment,
diuron
was
found
at
13.2­
95.2%
of
TRR
(
0.62­
1.21
ppm)
in
whole
plants,
4.1­
13.1%
of
TRR
(
0.20­
0.37
ppm)
in
foliage,
and
57.1­
70.4%
of
TRR
(
0.04­
0.22
ppm)
in
cobs;
very
minor
amounts
of
diuron
were
observed
in
kernels
(
2.4%
of
TRR,
<
0.01
ppm).
Following
preemergence
treatment,
diuron
was
detected
at
22.0­
48.4%
of
TRR
(
0.22­
1.15
ppm)
in
whole
plants
and
at
11%
of
TRR
(
0.35
ppm)
in
foliage;
diuron
was
not
detected
in
corn
cobs
or
kernels.
Other
residues
identified
in
corn
matrices
were
DCPMU
at
1.4­
46.4%
of
TRR
(<
0.01­
1.60
ppm)
and
DCPU
at
2.1­
50.0%
of
TRR
(
0.02­
2.22
ppm)
from
both
types
of
treatments.
No
other
metabolites
were
identified.
Polar
unknowns
accounting
for
0.5­
23.6%
of
TRR
(
0.01­
1.44
ppm)
in
whole
plants,
foliage,
cobs,
and
kernels
from
both
treatments
were
observed.

The
14C­
containing
residues
that
were
identified
in
wheat
were:
diuron,
at
34.2­
98.5%
TRR
(
0.12­
80.79
ppm)
in
wheat
forage
harvested
0­
71
days
posttreatment,
and
at
11.2%
TRR
(
0.002
ppm)
and
5.2%
TRR
(
0.051
ppm)
in
mature
wheat
grain
and
straw,
respectively.
The
diuron
metabolite
DCPMU
was
identified
at
7.7­
25.6%
TRR
(
0.002­
0.24
ppm)
in
all
wheat
commodities
except
forage
harvested
on
the
day
of
treatment,
and
DCPU
was
identified
at
1.2­
34.5%
TRR
(
0.02­
1.01
ppm)
in
all
wheat
commodities
except
mature
grain.
No
other
metabolites
were
identified.
Two
polar
unknowns
accounting
for
2.4­
34.9%
TRR
(
0.007­
0.023
ppm)
were
detected
in
wheat
forage
harvested
71
days
posttreatment
and
in
mature
grain
and
straw.
3
NH
N
O
Cl
Cl
CH
3
CH
3
NH
NH
O
Cl
Cl
CH
3
NH
NH
2
O
Cl
Cl
Diuron:
3­(
3,4­
dichlorophenyl)­
1,1­
dimethylurea
DCPMU;
IN­
15654:
3­(
3,4­
dichlorophenyl)­
1­
methylurea
DCPU;
IN­
R915:
3,4­
dichlorophenylurea
Figure
1.

Livestock
Commodities:

The
14C­
containing
residues
that
were
identified
in
lactating
goats
were:
The
principal
residue
identified
was
DCPU
which
comprised
10%
of
TRR
in
milk,
27%
of
TRR
in
fat,
35%
of
TRR
in
kidney,
23%
of
TRR
in
liver,
and
22%
of
TRR
in
muscle.
The
parent
and
other
dichloroaniline­
containing
metabolites
(
i.
e.,
3,4­
DCA
and
DCPMU)
were
detected
in
trace
quantities
(
#
0.01
ppm
each)
except
in
liver
(
0.12
ppm).
Four
minor
(
each
#
6%
of
TRR)
hydroxylated
metabolites
(
2­
OH­
DCA;
2­
OH­
DCPU;
2­
OHDCPMU
and
N­
acetyl­
2­
OH­
DCA)
were
also
detected;
these
metabolites
were
not
observed
in
plants
and
would
not
be
determined
by
the
enforcement
method.

The
major
portion
of
radioactive
residues
in
milk
was
comprised
of
several
conjugated
polar
components
which
collectively
accounted
for
56%
of
TRR.
These
polar
components
also
accounted
for
substantial
portions
of
the
total
radioactivity
in
liver
(
collectively
25%
of
TRR
)
and
kidney
(
collectively
23%
of
TRR).
Attempts
to
further
elucidate
the
nature
of
these
polar
materials
using
various
techniques
(
e.
g.,
enzyme
digestions,
heat
treatment)
were
not
successful.

Poultry:

The
14C­
containing
residues
that
were
identified
in
laying
hens
were:
DCPU,
which
comprised
-
45%
of
TRR
in
liver,
-
67­
75%
of
TRR
in
muscle,
-
47%
of
TRR
in
skin
with
fat,
-
57%
of
TRR
in
egg
yolk,
and
-
54%
of
TRR
in
egg
white.
The
parent,
other
dichloroaniline­
containing
metabolites
(
i.
e.,
DCPMU),
and
hydroxylated
metabolites
(
2­
OH­
diuron,
2­
OH­
DCA,
2­
OH­
DCPU,
2­
OHDCPMU
and
N­
acetyl­
2­
OH­
DCA)
were
identified
only
in
trace
quantities
(
mostly
at
#
0.01
ppm
each).

Adequate
radiovalidation
data
were
submitted
for
the
proposed
enforcement
method
for
animal
commodities.
The
GC
method
recovered
-
86
to
>
100%
of
the
TRR
in
liver,
kidney,
and
muscle;
however,
the
method
recovered
only
10%
of
the
TRR
in
milk
and
25%
of
the
TRR
in
fat.
The
low
4
recovery
in
milk
was
previously
addressed
(
DP
Barcodes
D195058
and
D195068,
11/
30/
93,
R.
Perfetti).
It
was
concluded
that
because
the
major
portion
of
radioactive
residues
in
milk
appear
to
be
hydroxy
metabolites
which
cannot
be
converted
to
DCA
and
do
need
not
be
quantitated,
a
new
method
would
not
be
required
for
milk.
Instead,
it
was
determined
that
the
levels
of
diuron
residues
in
milk
identified
in
the
ruminant
feeding
study
would
be
multiplied
by
10
to
account
for
all
of
the
exposure
in
the
risk
assessment.
The
low
recovery
in
fat
was
most
likely
due
to
the
low
residue
levels
present
in
fat.
In
a
separate
radiovalidation
study,
the
GC
method
recovered
-
62
to
77%
of
the
TRR
in
poultry
liver
and
muscle,
and
58
to
65%
of
the
TRR
in
egg
whites
and
yolks.

Dietary
Water
The
environmental
data
base
is
complete,
diuron
is
persistent
in
the
environment
and
has
potential
for
leaching
to
ground
and
surface
water.
The
metabolism
studies
of
diuron
in
a
variety
of
environmental
conditions
demonstrate
that
monochlorinated
methylphenyl
urea
(
MCMPU)
and
monochlorinated
dimethylphenyl
urea
(
MCDMPU)
can
be
formed
under
some
conditions
and
that
MCDMPU
is
a
major
degredate
in
aquatic
aeobic
and
anerobic
studies.
DCPMU
was
identified
as
a
major
degradate
in
several
studies
and
3,4­
DCA,
DCMU,
PDMU
were
identified
as
minor
metabolites.

The
MARC
raised
concerns
for
MCPDMU
based
on
an
analogous
compound,
monuron.
With
the
exception
of
the
position
of
the
chlorine,
the
structures
are
identical.
There
are
cancer
concerns
for
monuron
but
the
target
organs
are
different
than
those
effected
by
diuron.
The
MARC
recommended
that
a
separate
cancer
assessment
be
conducted
for
MCPDMU..

MARC
Decisions
&
Rationale
Plants:
The
MARC
concluded
that
for
tolerance
expression
and
risk
assessment
purposes,
the
residues
of
concern
in/
on
plants
are
diuron
and
its
metabolites
convertible
to
3,4­
dichloroaniline.
This
decision
was
based
on
the
assumption
that
the
metabolites
DCPMU,
and
DCPU
would
not
be
any
more
or
less
toxic
than
the
parent
and
in
consideration
of
the
analytical
methods
used
to
collect
field
trial
data
which
are
not
capable
of
measuring
each
metabolite
individually.
3,4­
Dichloroaniline
is
not
of
toxicological
concern
for
the
endpoints
regulated
for
diuron,
but
methods
specific
for
diuron,
DCPMU,
and
DCPU
are
not
widely
employed.
.
Livestock
Commodities:

The
MARC
concluded
that
for
the
tolerance
expression
and
risk
assessment
purposes,
the
residues
of
concern
in/
on
livestock
and
poultry
are
diuron
and
its
metabolites
convertible
to
3,
4­
dichloroaniline.
This
decision
was
based
on
the
5
assumption
that
the
metabolites
DCPMU
and
DCPU
would
not
be
any
more
or
less
toxic
than
the
parent
and
in
consideration
the
analytical
methods
used
to
collect
field
trial
data
which
are
not
capable
of
measuring
each
metabolite
individually.
To
account
for
the
poor
recovery
of
hydroxylated
metabolites
from
milk,
it
was
determined
that
the
levels
of
diuron
residues
in
milk
identified
in
the
ruminant
feeding
study
would
be
multiplied
by
10
to
account
for
all
of
the
exposure
to
diuron­
related
residues
in
the
risk
assessment.

Drinking
Water:
The
MARC
concluded
that
for
risk
assessment
purposes,
the
residues
of
concern
in
drinking
water
are
parent,
DCPMU,
and
MCPDMU.
Based
on
a
structural
analogy
to
monuron,
the
MARC
recommended
that
a
separate
cancer
assessment
be
conducted
for
MCPDMU.

cc:
JSPunzi
(
RRB2),
D.
Locke
(
RRB2),
Diuron
Reg.
Std.
File,
Diuron
SF,
RF,
LAN.
RD/
I:
RRB2
Chem
Review
Team
(
07/
11/
2001),
Alan
Nielsen
(
08/
31/
2001),
MARC
Chair
(
07/
11/
2001).
John
S.
Punzi:
7509C:
RRB2:
CM2:
Rm
712M:
703­
305­
7727:
07/
11/
2001.
