Document ID: EPA-HQ-OPP-2002-0188-0025
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-09-16T04:00Z

[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
1
of
9
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
05/
14/
2002
revised
07/
30/
2002
SUBJECT:
Hexazinone
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
TRED.

PC
Code:
107201
DP
Barcode:
D279898
REVIEWER:
John
S.
Punzi,
Ph.
D.,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(7509C)

THROUGH:
Richard
Griffin,
DESAC
Reviewer
Branch/
Health
Effects
Division
(7509C)

Alan
Nielsen,
Branch
Senior
Scientist
Branch/
Health
Effects
Division
(7509C)

TO:
Dirk
Helder,
Chemical
Review
Manager
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7509C)

and
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)

Executive
Summary
The
purpose
of
this
memorandum
is
to
report
the
revised
results
of
a
Tier
1
dietary
exposure
analysis
for
hexazinone.
In
this
analysis
the
acute
and
chronic
dietary
exposure
and
risk
estimates
resulting
from
food
intake
were
determined
for
the
U.
S.
population
and
various
population
subgroups.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
2
of
9
Acute
and
chronic
dietary
exposure
assessments
were
performed
in
order
to
determine
the
exposure
and
risk
estimates
which
result
from
the
use
of
hexazinone
on
the
crops
included
in
the
reregistration
eligibility
decision.
The
document
has
been
revised
to
reflect
a
07/
30/
02
HIARC
revist.

Hexazinone
residues
of
concern
for
plants
are
parent
plus
metabolites
A,
B,
C,
D,
E
(see
D279897,
S.
Kinard,
02/
05/
2002,
for
structures
and
metabolite
discussion).
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
enforcement
analytical
method's
limit
of
quantitation
(LOQ)
and
all
non
detectable
residues
were
found
in
residue
studies
(see
D279899,
J.
Punzi,
05/
15/
2002).
This
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.

Hexazinone
residues
of
concern
in
ruminant
milk
are
hexazinone
plus
metabolites
B,
C,
C­
2,
and
F.
Hexazinone
residues
of
concern
in
ruminant
tissue
are
hexazinone
plus
metabolites
B
and
F.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C­
1,
C­
2,
and
F.
The
livestock
feeding
study
indicates
significant
residues
in
milk
at
all
feeding
levels
and
quantifiable
residues
in
kidney.
When
the
residue
levels
are
corrected
for
exaggerated
rates
the
values
are
less
than
the
sum
of
the
LOQ's
for
the
residues
of
concern.
Based
on
the
analytical
method's
LOQ
the
residue
estimate
for
meats
and
milk
are
0.24
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.

The
chronic
dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
examined.
Exposures,
as
a
percentage
of
the
RfD,
ranged
from
approximately
3%
for
females
aged
13
through
50
years
to
15%
for
children
aged
1
through
6
years.

The
acute
dietary
risk
estimates
are
provided
for
the
population
subgroup
consisting
of
females
aged
13
through
50
years
only.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
this
subgroup.
Exposures
as
a
percentage
of
the
RfD
are
calculated
to
be
less
than
1%
at
the
95
th
percentile.

I.
Introduction
Dietary
risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
For
acute
and
chronic
assessments,
the
risk
is
expressed
as
a
percentage
of
a
maximum
acceptable
dose.
This
dose
is
the
highest
daily
dose
which
HED
has
deemed
will
pose
no
unreasonable
adverse
health
effects
and
is
called
the
population
adjusted
dose
(PAD).
The
PAD
is
equivalent
to
the
Reference
Dose
(RfD)
divided
by
the
FQPA
Safety
Factor.
Dietary
risk
is
expressed
as
a
percentage
of
the
PAD.
HED's
level
of
concern
is
exceeded
when
the
dietary
risk
exceeds
100%
of
the
PAD.
References
which
discuss
the
acute
and
chronic
risk
assessments
in
more
detail
are
available
on
the
EPA/
pesticides
web
site:
"Available
Information
on
Assessing
Exposure
from
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
3
of
9
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
http://
www.
epa.
gov/
fedrgstr/
EPA­
PEST/
2000/
July/
Day­
12/
6061.
pdf
;
or
see
SOP
99.6
(8/
20/
99).

II.
Residue
Information
Hexazinone
tolerances
are
established
under
40
CFR
§180.396
(a)
and
(b).
The
tolerance
for
plant
and
animal
commodities,
is
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).

Tolerances
are
currently
established
for;
alfalfa;
alfalfa
hay;
blueberries;
cattle,
goat,
hog,
and
horse
fat,
meat,
and
meat
by
products;
range
grasses,
pasture
grasses,
milk,
pineapple
and
sugarcane.
Current
tolerances
range
from
0.1
ppm
in/
on
meats
and
milk
to
10
ppm
on
grasses.

Reassessed
tolerances
range
from
0.1
ppm
to
4
ppm.
Tolerances
are
not
currently
needed
for
livestock
fat,
hog
meat,
and
hog
meat
by
products.
HED
is
recommending
that
in
order
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
and
to
compute
a
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock,
uses
on
pasture
and
rangeland
grasses
must
be
revoked.
A
MTDB
could
not
be
calculated
including
grass
and
grass
hay
since
additional
residue
data
are
required
for
use
patterns
in
which
significant
residues
are
expected
in/
on
the
RACs.
HED
recognizes
that
the
estimated
100,000
acres
of
pasture
and
rangeland
treated
with
hexazinone
is
relatively
low.
Since
grass
and
grass
hay
are
considered
major
dietary
components
of
ruminants
(up
to
60%
of
the
diet
per
current
OPPTS
GLN)
a
MTDB
for
livestock
could
not
be
developed
when
grasses
are
included
in
the
registered
uses.
HED
has
determined
that
a
MTDB
could
be
constructed
from
other
potential
feed
items
for
livestock
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.

Hexazinone
residues
of
concern
for
plants
are
parent
plus
metabolites
A,
B,
C,
D,
E
(see
D279897,
S.
Kinard
02/
05/
2002,
for
structures
and
metabolite
discussion).
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
analytical
method's
limit
of
quantitation
(LOQ)
and
all
non
detectable
residues
were
found
in
residue
studies
(see
D279899,
J.
Punzi,
05/
05/
2002).
This
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.

Hexazinone
residues
of
concern
in
ruminant
milk
are
hexazinone
plus
metabolites
B,
C,
C­
2,
and
F.
Hexazinone
residues
of
concern
in
ruminant
tissue
are
hexazinone
plus
metabolites
B
and
F.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C­
1,
C­
2,
and
F.
The
livestock
feeding
study
indicates
significant
residues
in
milk
at
all
feeding
levels
and
quantifiable
residues
in
kidney.
When
the
residue
levels
are
corrected
for
exaggerated
rates
the
values
are
less
than
the
sum
of
the
LOQ's
for
the
residues
of
concern.
Based
on
the
analytical
method's
LOQ
the
reside
estimate
for
meats
and
milk
are
0.24
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
4
of
9
Residue
Data
used
for
Acute
and
Chronic
Assessments:

This
TIER
1
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C­
1,
C­
2,
and
F.
The
same
data
are
being
used
in
both
acute
and
chronic
analysis.

III.
DEEM™
Program
and
Consumption
Information
Hexazinone
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software,
Version
[7.76],
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989­
1992.
The
1989­
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples­
cooked/
canned
or
wheat­
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.

For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(e.
g.,
orange
or
orange­
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
(i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.

HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(e.
g.,
nursing
and
non­
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
5
of
9
subpopulations
were
included
in
representative
populations
having
sufficient
numbers
of
survey
respondents
(e.
g.,
all
infants,
or
females
13­
50
years).

IV.
Toxicological
Information
The
toxicological
endpoint
summary
table
below
reflects
the
HIARC
document
(01/
16/
2002,
TXR#
0050371),
the
FQPA
SF
committee
report
(05/
15/
2002,
TXR#
0050750)
and
an
additional
HIARC
meeting
on
07/
30/
02.

Table
1.
Summary
of
Toxicological
Doses
and
Endpoints
for
[CHEMICAL]
for
Use
in
Dietary
Exposure
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF*
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
[Female
13­
50]
NOAEL
=
[400]
mg/
kg/
day
UF
=
[100]
Acute
RfD
=
[4.0]
mg/
kg/
day
FQPA
SF
=
[1]
aPAD
=[
4.0]
mg/
kg/
day
[Developmental
Toxicity­
Rat]
LOAEL
=
[
900]
mg/
kg/
day
based
on
[decreased
fetal
weight,
malformation
of
kidneys]

Chronic
Dietary
all
populations
NOAEL=
[5]
mg/
kg/
day
UF
=
[100]
Chronic
RfD
=
[0.05]
mg/
kg/
day
FQPA
SF
=
[1]
cPAD
=
[0.05]
mg/
kg/
day
[Chronic
One
Year
Feeding­
Dog]
LOAEL
=
[
~40]
mg/
kg/
day
based
on
[hepatotoxicity]

V.
Results/
Discussion
As
stated
above,
for
acute
and
chronic
assessments,
HED's
level
of
concern
is
exceeded
when
the
dietary
risk
exceeds
100%
of
the
PAD.
The
DEEM
analyses
can
estimate
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table
2
are
for
the
appropriate
subpopulation,
females
aged
13
to
50
years.
The
results
reported
in
Table
3
are
for
the
U.
S.
Population
(total),
all
infants
(<
1
year
old),
children
1­
6,
children
7­
12,
females
13­
50,
males
13­
19,
males
20+,
and
seniors
55+.
The
results
for
the
other
population
subgroups
are
included
in
the
appendices.
They
are
not
included
in
the
tables
because
the
numbers
of
respondents
in
the
other
subgroups
were
not
sufficient;
and
therefore,
the
exposure
estimates
for
these
subgroups
contained
higher
levels
of
uncertainty.
However,
the
respondents
in
these
subgroups
were
also
part
of
larger
subgroups
which
are
listed
in
the
Tables.
For
example,
nursing
and
non­
nursing
infants
are
included
in
all
infants.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
6
of
9
Results
of
Acute
Dietary
Exposure
Analysis
Results
are
reported
at
the
95th
percentile
of
exposure
because
the
assessment
incorporated
100%
CT.
The
acute
dietary
risk
estimates
are
provided
for
the
population
subgroup
consisting
of
females
aged
13
through
50
years
only.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
this
subgroup.
Exposures
as
a
percentage
of
the
RfD
are
calculated
to
be
less
than
1%
at
the
95
th
percentile.

Table
2.
Results
of
Acute
Dietary
Exposure
Analysis
at
the
95
th
Percentile
of
Exposure
Population
Subgroup
aPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
aPAD
Females
13­
50
years
old
4.
0
0.003611
<1
Results
of
Chronic
Dietary
Exposure
Analysis
Table
3.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
(total)
0.
05
0.
002167
4
All
Infants
(<
1
year)
0.
05
0.
003752
7
Children
1­
6
years
0.
05
0.
007449
15
Children
7­
12
years
0.
05
0.
003964
8
Females
13­
50
0.05
0.001308
3
Males
13­
19
0.05
0.002334
5
Males
20+
years
0.
05
0.
001208
2
Seniors
55+
0.05
0.001159
2
The
chronic
dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
examined.
Exposures,
as
a
percentage
of
the
RfD,
ranged
from
approximately
3%
for
females
aged
13
through
50
years
to
15%
for
children
aged
1
through
6
years.
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9
VII.
Conclusions
The
Tier
1
acute
and
chronic
dietary
risk
assessments
were
conducted
for
all
supported
hexazinone
food
uses.
Dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
for
all
supported
registered
commodities,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
at
the
95
th
exposure
percentile
for
the
population
subgroup
consisting
of
females
aged
13
to
50
years.
The
acute
dietary
exposure
estimate
for
this
group
is
<1%
of
the
aPAD.
This
assessment
also
concludes
that
for
all
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
U.
S.
population
(total)
(4%
of
the
cPAD)
and
all
population
subgroups.
The
most
highly
exposed
population
subgroup
is
children
aged
1
to
6
years.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
is
15%
of
the
cPAD.
[Hexazinone]
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9
Appendix
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
HEXAZINONE
(1989­
92
data)
Residue
file
name:
C:\
WINDOWS\
Desktop\
hexazinone\
107201accr.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date
07­
31­
2002/
14:
53:
38
Residue
file
dated:
07­
31­
2002/
14:
52:
49/
8
Reference
dose
(RfD,
Chronic)
=
.05
mg/
kg
bw/
day
===============================================================================
Total
exposure
by
population
subgroup
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

Total
Exposure
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
­­­­­­­­­­­­­
­­­­­­­­­­­­­­

U.
S.
Population
(total)
0.002167
4.3%

U.
S.
Population
(spring
season)
0.002199
4.4%
U.
S.
Population
(summer
season)
0.002113
4.2%
U.
S.
Population
(autumn
season)
0.002263
4.5%
U.
S.
Population
(winter
season)
0.002095
4.2%

Northeast
region
0.002137
4.3%
Midwest
region
0.002400
4.8%
Southern
region
0.001990
4.0%
Western
region
0.002215
4.4%

Hispanics
0.002339
4.7%
Non­
hispanic
whites
0.002172
4.3%
Non­
hispanic
blacks
0.001975
4.0%
Non­
hisp/
non­
white/
non­
black
0.002334
4.7%

All
infants
(<
1
year)
0.003752
7.5%
Nursing
infants
0.001188
2.4%
Non­
nursing
infants
0.004830
9.7%
Children
1­
6
yrs
0.007449
14.9%
Children
7­
12
yrs
0.003964
7.9%

Females
13­
19
(not
preg
or
nursing)
0.001829
3.7%
Females
20+
(not
preg
or
nursing)
0.001143
2.3%
Females
13­
50
yrs
0.001308
2.6%
Females
13+
(preg/
not
nursing)
0.001968
3.9%
Females
13+
(nursing)
0.002252
4.5%

Males
13­
19
yrs
0.002335
4.7%
Males
20+
yrs
0.001208
2.4%
Seniors
55+
0.001160
2.3%
Pacific
Region
0.002206
4.4%

­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
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PC
Code:
[107201]
Page:
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of
9
Attachment
(electronic
file
id
107201accr.
rs7).

cc:
JSPunzi
(RRB2),
Hexazinone
Reg.
Std.
File,
Hexazinone
SF,
RF,
LAN.
7509C:
RRB2:
John
S.
Punzi:
CM2:
Rm
712M:
703­
305­
7727:
05/
15/
2002.
(Revised
07/
31/
02).