OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
DATE:
April
25,
2002
SUBJECT:
Hexazinone.
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
for
Water.
PC
code
107201;
Rereg.
Case
0266;
DP
Barcode:
D282111;
TXR
No.
0050425.

FROM:
Sherrie
L.
Kinard,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(7509C)

THROUGH:
Al
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(7509C)

TO:
Christine
Olinger,
Chair
Metabolism
Assessment
Review
Committee
(MARC)
Health
Effects
Division
(7509C)

MATERIAL
REVIEWED
The
MARC
met
on
January
29,
2002
and
then
again
on
March
12,
2002
to
consider
residues
of
hexazinone
[3­
cyclohexyl­
6­(
dimethylamino)­
1­
methyl­
1,3,5­
triazine­
2,4(
1H,
3H)­
dione]
and
metabolites
in/
on
plant
and
animal
comodities
and
in
water.
Specifically,
MARC
determined
which
metabolites
should
be
included
in
the
tolerance
expression
and
risk
assessment.

MARC
CONCLUSIONS
The
Committee
concluded
that
hexazinone
plus
metabolites
A,
B,
C,
D,
and
E
(calculated
as
hexazinone)
are
the
residues
of
concern
to
be
included
in
tolerance
expression
and
risk
assessment
for
plants
and
rotational
crops.
The
residues
of
concern
to
be
included
in
the
tolerance
expression
for
ruminants
are
hexazinone
plus
metabolites
B,
C,
C­
2,
and
F
in
milk,
and
hexazinone
plus
metabolites
B
and
F
in
tissue.
For
purposes
of
risk
assessment,
the
residues
of
concern
in/
on
ruminants
are
hexazinone
plus
metabolites
B,
C,
C­
1,
C­
2,
and
F.
The
Agency
has
previously
determined
that
tolerances
in
poultry
commodities
and
a
poultry
feeding
study
are
not
required
for
reregistration
based
on
results
of
reviewed
poultry
metabolism
data.

For
water,
the
Committee
concluded
that
for
risk
assessment
purposes,
hexazinone,
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings
should
be
included.
Hexazinone
HED
MARC
Meeting
Summary
Chart:
Chemical:
Hexazinone
Date:
29­
Jan­
2002
Residues
of
Concern
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Plants
Parent,
metabolites
A,
B,
C,
D,
and
E
Parent,
metabolites
A,
B,
C,
D,
and
E
Rotational
crop
Parent,
metabolites
A,
B,
C,
D,
and
E
Parent,
metabolites
A,
B,
C,
D,
and
E
Poultry
Not
Required
Not
Required
Ruminant
Parent,
metabolites
B,
C,
C­
1,
C­
2,
and
F
For
milk:
Parent,
B,
C,
C­
2
and
F
For
tissue:
Parent,
B,
and
F
Water
Not
discussed
N/
A
Chemical:
Hexazinone
Date:
12­
March­
2002
Residues
of
Concern
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Water
Parent,
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings.
N/
A
RATIONALE
Plant:
Hexazinone
and
metabolites
A,
B,
C,
D,
and
E
are
detected
in
plant
metabolism
studies.
Toxicity
data
are
not
available
for
these
metabolites,
and
MARC
assumed
they
have
potentially
similar
toxicity
to
the
parent
due
to
the
similarities
in
structure.
These
metabolites
are
also
measured
by
the
enforcement
method;
in
addition,
metabolites
A­
D
and
F
were
observed
in
the
rat
metabolism
study.
MARC
concluded
that
for
risk
assessment
and
tolerance
expression,
hexazinone
plus
metabolites
A,
B,
C,
D,
and
E
are
the
residues
of
concern.

Rotational
crop:
Hexazinone
and
metabolites
F,
G,
H,
G3170,
G3170­
NG,
A­
1,
1,
and
C­
1
were
also
found
in
field
rotational
crop
studies,
in
addition
to
the
parent,
A,
B,
C,
D,
and
E;
however,
metabolites
F,
G,
H,
G3170,
G3170­
NG,
A­
1,
1,
and
C­
1
were
below
the
LOQ
in
the
field
studies.
The
MARC
concluded
that
these
low
level
metabolites
are
not
likely
to
be
significantly
more
toxic
than
the
parent
and
can
therefore
be
excluded.

Ruminant:
Metabolites
B,
C­
1,
C­
2,
and
F
are
the
major
metabolites
(>
10%
TRR)
found
in
milk
and
tissue
in
the
goat
metabolism
study;
therefore,
the
MARC
concluded
that
hexazinone
plus
these
metabolites
need
to
be
included
in
the
risk
assessment.
Since
the
enforcement
method
detects
only
parent,
B,
C,
C­
2,
and
F
in
milk,
and
parent,
B,
and
F
in
tissues,
MARC
recommended
that
for
milk
tolerance
expression,
the
residues
of
concern
are
hexazinone
plus
metabolites
B,
C,
C­
2,
and
F,
and
for
livestock
tissues
tolerance
expression,
the
residues
of
concern
are
hexazinone
plus
metabolites
B,
and
F.
Although
the
Committee
previously
(5/
19/
94)
recommended
inclusion
of
metabolites
A,
D
and
E
in
animal
commodities,
these
moieties
each
represented
<1
to
4%
of
the
total
residues
in
goat
milk
and
tissues.

Poultry:
No
decision
is
needed
at
this
time
(40CFR180.6(
a)
(3)).

Water:
Environmental
fate
data
suggest
that
the
parent
and
degradates
are
likely
to
be
persistent
and
mobile
in
the
environment.
Leaching
and
runoff
are
expected
to
be
primary
dissipation
routes.
Metabolites
A,
B,
D,
1
(JS472),
and
2
(JT677)
are
major
metabolites
(>
10%
TRR)
found
in
soil/
aquatic
studies.
Metabolites
A­
1,
C
and
G3170
are
detected
in
ground
water
analysis.
Due
to
lack
of
toxicity
data
for
these
metabolites,
MARC
assumes
they
have
similar
toxicity
as
the
parent
because
of
the
structure
similarities
(except
G3170).
G3170
was
detected
at
the
highest
level
in
the
California
prospective
groundwater
study
(PGW)
and
there
are
no
toxicity
information
available
to
indicated
that
it
is
of
less
toxicological
concern
than
the
parent.
Therefore,
MARC
concludes
that
parent,
G3170,
and
all
degradates
with
conjoined
cyclohexyl
and
triazine
rings
(specifically,
A,
A­
1,
B,
C,
D,
1
(JS472),
and
2
(JT677))
are
residues
of
concern
for
risk
assessment
in
water.

ATTENDEES
Members
in
Attendance
(January
29,
2002):
Abdallah
Khasawinah,
Yan
Donovan,
David
Nixon,
Rick
Loranger,
Leung
Cheng,
John
Doherty,
Sheila
Piper,
Bill
Wassell,
William
Dykstra
(alternate).

Members
Not
Present:
Alberto
Protzel,
Christine
Olinger,
Norman
Birchfield.

Non­
Members
in
Attendance:
David
Anderson,
Sherrie
Kinard,
Diana
Locke,
Dirk
Helder,
Pauline
Wagner,
Larry
Liu.

Members
in
Attendance
(March
12,
2002):
Abdallah
Khasawinah,
Christine
Olinger,
Norman
Birchfield,
Yan
Donovan,
David
Nixon,
Rick
Loranger,
Leung
Cheng,
John
Doherty,
Sheila
Piper.

Members
Not
Present:
Bill
Wassell,
Alberto
Protzel,
Leonard
Keifer.

Non­
Members
in
Attendance:
Dirk
Helder,
Sherrie
Kinard,
Larry
Liu.

cc:
SF,
RF,
List
A
File,
S.
Kinard
(RRB2),
D.
Anderson
(RRB2),
Diana
Locke
(RRB2),
L.
Liu
(EFED)
RDI:
C.
Olinger:
04/
25/
02;
A.
Nielson:
04/
25/
02.

7509C:
RRB2:
S.
Kinard:
CM#
2:
Rm
722B:
703­
305­
0563:
04/
25/
02.
