Document ID: EPA-HQ-OPP-2002-0188-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-09-16T04:00Z

HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
HED
CHAPTER
–
6/
5/
02
DuPONT
COMMENTS
1.0
Executive
Summary
The
most
significant
recommendation,
in
our
view,
contained
in
the
draft
documents
pertains
to
the
revocation
tolerances
and
associated
use
of
hexazinone
on
grass.
We
acknowledge
that
guidelines
and
interpretations
regarding
the
practicality
of
grower
control
over
cattle
grazing
intervals
have
changed
since
data
supporting
this
use
pattern
were
last
submitted.
However,
as
indicated
in
your
review,
this
is
a
rather
minor
use
and
our
information
indicates
that
the
current
label
restrictions
regarding
cutting
and
grazing
are
being
complied
with.
Therefore,
the
tolerances
supporting
the
use
are
sufficient.
Given
the
above,
we
request
that
the
existing
tolerances
and
use
pattern
be
maintained
while
we
conduct
new
residue
work
to
support
EPA's
interpretation
regarding
a
zero
day
grazing
interval.

We
understand
that
our
recently
submitted
Rabbit
Developmental
Toxicity
Study
(DuPont­
7405,
MRID
45677801)
was
not
reviewed
in
time
to
be
included
in
the
Draft
TRED.
In
view
of
the
pivotal
importance
of
study
to
the
overall
conclusions
of
the
final
TRED
(specifically,
the
current
proposal
to
declare
a
significant
gap
in
the
toxicology
data
base,
the
selection
of
appropriate
end
points
for
regulatory
purposes
and
the
imposition
an
additional
10X
safety
factor
due
to
an
incomplete
data
base),
we
respectfully
request
that
this
study
be
reviewed
as
quickly
as
possible
to
be
included
in
the
final
TRED.

We
also
note
in
the
toxicology
review
that
"Gene
mutation
–
bacterial"
is
listed
as
an
unsatisfied
requirement.
have
recently
submitted
(June
28,
2002,
no
MRID
yet
assigned)
a
new
Ames
assay
with
the
75
DF
formulation
which
we
believe
will
satisfy
this
requirement.

Finally,
we
do
not
believe
a
28­
day
inhalation
study
should
be
required
until
the
existing
and
submitted
21­
day
inhalation
study
(MRID
00063972)
has
been
reviewed.

3.0
Hazard
Characterization
3.1
Hazard
Profile
Table
1:
Acute
Toxicity:
For
Inhalation
LC50>
3.94
mg/
L
(4
hour),
add
(25%
formulation)

Table
2:
Toxicity
Profile:

870.3465,
"A
28­
day
inhalation
study
is
required."

As
noted
in
the
HIARC
document,
an
unreviewed
21­
day
inhalation
study
is
available
(MRID
00063972)
which
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risks
and
that
no
further
inhalation
testing
should
be
required.
The
Registrant
requests
that
existing
data
be
reviewed
before
additional
testing
is
required.

870.3700b
Prenatal
Developmental
Toxicity
Unacceptable/
Upgradeable.
The
registrant
has
submitted
a
new
rabbit
developmental
study
(DuPONT­
7405,
MRID
45677801)
which
addressed
the
deficiencies
and
supports
the
conclusions
of
the
original
study
870.5100
Reverse
mutation
in
Samonella
Strains
Unacceptable:
DuPont
has
conduct
a
Ames
assay
for
the
75DF
formulation
in
both
Salmonella
and
E.
Coli
at
up
to
5000
ug/
plate
(=
3750
ug/
plate
a.
i.)
that
can
be
submitted,
if
needed,
to
satisfy
this
requirement.
The
results
were
negative
for
gene
mutations
in
both
species.

870.5385
In
vivo
Rat
Bone
Marrow
Cytogenetics
Assay
Unacceptable.
Add,
"However
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."

3.2
FQPA
Considerations
and
3.3
Dose
Response
Assessment:
Acute
Reference
Dose
Females
13­
50
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
new
rabbit
developmental
study
(DuPont­
7405,
MRID
45677801)
to
the
Agency
which
addresses
the
deficiencies
and
supports
the
previous
study.
Once
the
new
rabbit
study
is
reviewed,
the
registrant
believes
the
extra
10x
uncertainty
factor
should
be
removed.

5.1
Acute
Aggregate
Risk
Assessment
The
headings
for
the
last
three
columns
for
Table
11
(page
42)
should
specify
ug/
l
rather
than
g/
l.