HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
REPORT
OF
THE
FQPA
SAFETY
FACTOR
COMMITTEE
­
5/
15/
02
DuPONT
COMMENTS
I.
HAZARD
IDENTIFICATION
3.
Degree
of
Concern
and
Residual
Uncertainties
For
setting
the
acute
reference
dose
(ARfD)
for
females
of
childbearing
age,
the
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
UFdb
factor
of
10x
rather
than
3x
was
used
because,
based
on
extrapolation
to
the
rabbit
pilot
NOEL
of
50
mg/
kg
in
the
previous
study,
it
was
concluded
the
difference
between
rabbits
and
rats
may
be
greater
than
3x.

Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont­
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOAEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOAEL
was
125
mg/
kg/
day
based
on
weight
effects,
which
were
only
slight
in
the
fetus.
A
higher
dose,
175
mg/
kg/
day
produced
severe
maternal
toxicity.

Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
