TXR
NO.
0051049
August
08,
2002
MEMORANDUM
SUBJECT:
HEXAZINONE
­
2
nd
Report
of
the
FQPA
Safety
Factor
Committee.

NOTE:
THIS
REPORT
REPLACES
THE
PREVIOUS
REPORT
OF
THE
FQPA
SAFETY
FACTOR
COMMITTEE
DATED
MAY
15,
2002
(HED
DOC.
NO.
0050750).

FROM:
Brenda
Tarplee,
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)

THROUGH:
Ed
Zager,
Chairman
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)

TO:
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(7509C)

PC
Code:
107201
The
Health
Effects
Division
(HED)
FQPA
Safety
Factor
Committee
(SFC)
met
on
August
5,
2002
to
reevaluate
the
hazard
and
exposure
data
for
Hexazinone
with
regard
to
making
a
decision
on
the
additional
safety
factor
for
the
protection
of
infants
and
children.
The
SFC
concluded
that,
based
on
reliable
data,
no
additional
safety
factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Hexazinone
exposures
and
risks.
This
report
replaces
the
previous
report
of
the
FQPA
Safety
Factor
Committee
dated
May
15,
2002
(HED
Doc.
No.
107201).
2
I.
HAZARD
ASSESSMENT
On
July
30,
2002,
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reevaluated
the
toxicity
endpoints
selected
for
Hexazinone
risk
assessment
as
well
as
the
FQPA
assessment
in
light
of
newly
reviewed
data:
rabbit
developmental
toxicity
study.
The
following
summarizes
the
conclusions
of
the
committee
at
this
meeting.

1.
Adequacy
of
the
Toxicology
Database
On
July
30,
2002,
the
HIARC
concluded
that
the
toxicology
data
base
for
Hexazinone
contains
acceptable
guideline
prenatal
developmental
toxicity
studies
in
the
rat
and
the
rabbit
as
well
as
an
acceptable
guideline
2­
generation
reproduction
study
conducted
in
rats.
In
addition,
the
HIARC
concluded
that
a
developmental
neurotoxicity
study
with
Hexazinone
is
not
required.

2.
Determination
of
Susceptibility
The
data
provided
no
indication
of
increased
susceptibility
of
rats
or
rabbits
to
in
utero
and/
or
postnatal
exposure
to
Hexazinone.
The
recently
submitted
rabbit
developmental
study
showed
fetal
weight
decrement
at
the
same
dose
as
maternal
weight
decrement.

3.
Degree
of
Concern
and
Residual
Uncertainties
The
HIARC
concluded
that
there
are
no
residual
uncertainties
for
pre­
and/
or
post­
natal
toxicity
in
any
of
the
available
studies
with
Hexazinone.

II.
EXPOSURE
ASSESSMENT
No
changes
were
made
in
the
exposure
assessment
since
the
last
review
for
Hexazinone.

1.
Dietary
(Food)
Exposure
Considerations
(Correspondence:
C.
Christensen
to
B.
Tarplee
dated
April
3,
2002
and
May
1,
2002;
dietary
food
responses
provided
by
S.
Kinard
and
J.
Punzi)

Hexazinone
is
a
contact
and
residual
herbicide
used
to
control
many
annual,
biennial
and
perennial
weeds
and
woody
plants.
Tolerances
are
currently
established
for
combined
residues
of
Hexazinone
and
its
metabolites
in
or
on
alfalfa,
pasture
and
range
grasses,
blueberries,
pineapple,
sugarcane,
molasses,
milk
and
meat
(40
CFR§
180.396).

On
January
29,
2002
and
March
12,
2002,
the
HED
Metabolism
Assessment
Review
Committee
(MARC)
met
to
determine
which
metabolites
should
be
included
in
the
tolerance
expression
and
risk
assessment
for
Hexazinone.
The
MARC
concluded
that:
parent
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.
Additionally,
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
3
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
(April
3,
2002;
Draft
memo
provided
to
FQPA
SFC).

The
HED
Dietary
Exposure
Evaluation
Model
(DEEM)
is
used
to
assess
the
risk
from
dietary
exposure
to
Hexazinone
residues
in
food.
These
are
currently
Tier
1
analyses
based
on
tolerance
level
residues
and
assuming
that
100%
of
crops
are
treated
with
Hexazinone.

Since
there
are
data
gaps
for
the
magnitude
of
the
residues
of
Hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
pasture
and
range
grass
(forage
and
hay),
tolerances
established
for
these
feed
items
and
for
secondary
residues
in/
on
milk
and
meat,
cannot
be
reassessed.
Therefore,
HED
is
recommending
that
the
use
on
pasture
and
range
grasses
be
discontinued
and
that
tolerances
resulting
from
these
uses
be
revoked.
The
FQPA
SFC
based
its
safety
factor
recommendation
on
the
assumption
that
the
use
of
Hexazinone
on
pasture
and
range
grasses
is
withdrawn
and
all
established
tolerances
associated
with
this
use
are
revoked.

2.
Dietary
(Drinking
Water)
Exposure
Considerations
(Correspondence:
C.
Christensen
to
B.
Tarplee
dated
April
3,
2002;
dietary
water
responses
provided
by
J.
Melendez
and
L.
Liu)

The
environmental
fate
database
is
adequate
and
indicate
that
Hexazinone
is
persistent
and
mobile
in
soil
and
aquatic
environments.
The
mobility
of
Hexazinone
was
demonstrated
in
batch
equilibrium
data
and
confirmed
in
field
and
forestry
dissipation
data.
The
batch
equilibrium
data
also
suggest
that
its
degradates
are
very
mobile.
Therefore,
Hexazinone
and
its
degradates
may
be
of
concern
for
surface
water
and
groundwater
contamination.

On
January
29,
2002
and
March
12,
2002,
the
HED
Metabolism
Assessment
Review
Committee
(MARC)
concluded
that
Hexazinone,
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings
should
be
included
in
the
drinking
water
risk
assessment
for
Hexazinone.
The
following
degradates
were
detected
in
the
laboratory
fate
studies
and/
or
monitored
in
the
field
dissipation
and
the
groundwater
study:
A,
A­
1,
C,
D,
1,
2,
and
G3170.

The
registrant
submitted
a
small­
scale
prospective
groundwater
monitoring
study
for
Hexazinone.
The
study
was
conducted
in
a
field
of
alfalfa
underlain
with
sandy
soil
in
Merced
County,
California.
The
site
is
located
within
the
recharge
area
for
a
shallow
unconfined
aquifer.
The
organic
matter
content
of
the
soil
was
#
0.7%,
the
pH
was
7.5­
8.9
in
the
upper
1.5
feet,
and
there
were
no
continuous
impeding
layers.
Results
indicated
that
Hexazinone
and
its
degradates
are
very
mobile
and
persistent.
The
maximum
total
residue
detected
in
the
groundwater
study
is
used
in
the
risk
assessment
and
is
supported
by
modeling
output.
4
The
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
in
the
State
of
Maine
conducted
a
statewide
assessment
to
determine
the
impact
of
highly
leachable
pesticides
(including
Hexazinone,
a
herbicide
used
in
the
production
of
blueberries)
on
surface
water
and
ground
waters
in
Maine.
Although
the
total
amounts
of
Hexazinone
used
on
blueberries
in
Maine
is
very
low
(only
approximately
1%
of
the
total
sale
in
the
U.
S.),
the
chemical
was
detected
in
groundwater
and
surface
water
at
very
high
frequency.
Degradate
B
was
also
detected
in
surface
water
and
groundwater;
however,
no
detailed
information
was
provided.

Tier
I
modeling
was
used
to
estimate
the
maximum
concentrations
of
Hexazinone
likely
to
be
found
in
surface
(FIRST)
and
ground
(SCIGROW)
waters.
The
models
used
take
into
consideration
the
percent
area
crop
and
the
index
reservoir.
Because
of
the
high
mobility
of
Hexazinone,
and
its
high
solubility,
it
appears
that
the
chemical
may
be
preferentially
dissolved
in
the
ponds,
rivers
and
reservoirs
(as
opposed
to
adsorbed
to
sediments).
It
is
noted
that
the
SCIGROW
result
obtained
is
of
the
same
order
of
magnitude
than
the
results
obtained
in
the
prospective
groundwater
study.

3.
Residential
Exposure
Considerations
(Correspondence:
C.
Christensen
to
B.
Tarplee
dated
April
3,
2002)

There
are
currently
no
registered
residential
uses
of
Hexazinone.

III.
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
1.
FQPA
Safety
Factor
Recommendations
The
FQPA
SFC
recommends
that
OPP
depart
from
the
default
10X
additional
safety
factor
and
instead
use
a
different
additional
safety
factor
of
1X.
This
recommendation
is
based
on
reliable
data
supporting
the
findings
set
forth
below.

A.
Traditional
Additional
Safety
Factor
(Addressing
Data
Deficiencies)

On
July
30,
2002,
the
HIARC
found
no
data
deficiencies
and
hence
concluded
that
no
additional
traditional
safety
factors
were
needed
with
regard
to
the
completeness
of
the
Hexazinone
toxicity
database
(See
Section
I.
1.).

B.
Special
FQPA
Safety
Factors
The
FQPA
SFC
recommended,
that
no
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Hexazinone
exposure
and
risks.

2.
Rationale
and
Findings
Regarding
Recommendation
on
Special
FQPA
Safety
Factor
The
Committee
concluded
that
no
Special
FQPA
safety
factor
was
needed
because:
5
The
toxicology
database
for
Hexazinone
contains
acceptable
guideline
developmental
and
reproduction
studies
and
these
studies
demonstrate
that
there
is
no
concern
for
quantitative
or
qualitative
increased
susceptibility
of
the
young.
The
HIARC
concluded
that
a
developmental
neurotoxicity
study
with
Hexazinone
is
not
required.

There
are
no
residual
uncertainties
identified
in
the
exposure
databases.
The
dietary
food
exposure
assessment
is
Tier
1,
screening
level,
which
is
based
on
tolerance
level
residues
and
assumes
100%
of
all
crops
are
treated
with
Hexazinone.
The
dietary
drinking
water
assessment
uses
monitoring
data
(ground
water)
and
modeling
results
(surface
water)
based
on
chemical­
specific
data
and
include
extrapolated
estimates
for
all
degradates
of
concern.
These
assessments
will
not
underestimate
the
exposure
and
risks
posed
by
Hexazinone.

NOTE:
This
safety
factor
recommendation
is
based
on
the
assumption
that
the
use
of
Hexazinone
on
pasture
and
range
grasses
is
withdrawn
(due
to
the
lack
of
field
trial
residue
data
for
forage
and
hay)
and
that
all
established
tolerances
associated
with
this
use
are
revoked.

3.
Application
of
the
FQPA
Safety
Factors
(Population
Subgroups
/
Risk
Assessment
Scenarios)

The
FQPA
SFC
recommends
that
no
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Hexazinone
exposure
and
risks.
This
recommendation
is
applicable
to
all
population
subgroups
for
all
exposure
routes
and
durations.
No
other
FQPA
safety
factor
would
be
appropriate
for
Hexazinone.
6
4.
Summary
of
FQPA
Safety
Factors
Summary
of
FQPA
Safety
Factors
for
Hexazinone
LOAEL
to
NOAEL
(UFL)
Subchronic
to
Chronic
(UFS)
Incomplete
Database
(UFDB)
Special
FQPA
Safety
Factor
(Hazard
and
Exposure)

Magnitude
of
Factor
1X
1X
1X
1X
Rationale
for
the
Factor
No
LOAEL
to
NOAEL
extrapolations
performed
No
subchronic
to
Chronic
extrapolations
performed
Database
is
sufficiently
complete
to
assess
risks
to
infants
and
children.
No
residual
concerns
regarding
pre
or
post­
natal
toxicity
or
completeness
of
the
toxicity
or
exposure
databases
Endpoints
to
which
the
Factor
is
Applied
Not
Applicable
Not
Applicable
Not
Applicable
Not
Applicable
