Document ID: EPA-HQ-OPP-2002-0309-0013
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-12-03T05:00Z

1
See
memo
­
Deriving
Q
1
*
s
Using
the
Unified
Interspecies
Scaling
Factor,
P.
A.
Fenner­
Crisp,
Director,
HED,
7/
1/
94.
HED
DOC.
NO.
014450
MEMORANDUM
January
23,
2001
SUBJECT:
REVISED
Oxadiazon
Quantitative
Risk
Assessment
(
Q
1
*)
Based
On
ICR­
JCL
Mouse
and
SPF
Wistar
Rat
Dietary
Studies
With
3/
4'
s
Interspecies
Scaling
Factor
P.
C.
Code
109001
TO:
Nancy
McCarroll,
Geneticist
Toxicology
Branch
Health
Effects
Division
(
7509C)

FROM:
Lori
L.
Brunsman,
Statistician
Science
Information
Management
Branch
Health
Effects
Division
(
7509C)

THROUGH:
Jess
Rowland,
Branch
Chief
Science
Information
Management
Branch
Health
Effects
Division
(
7509C)

Conclusion
The
most
potent
unit
risk,
Q
1
*(
mg/
kg/
day)­
1,
of
those
calculated
for
Oxadiazon
is
that
for
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
at
5.52
x
10­
2
in
human
equivalents.
The
dose
levels
used
from
the
98­
week
dietary
study
were
0,
3,
10,
100,
and
1000
ppm
of
Oxadiazon.
The
corresponding
tumor
rates
were
3/
51,
1/
55,
4/
57,
11/
58,
and
29/
55,
respectively.

Background
On
September
3,
1986,
the
Toxicology
Branch
Peer
Review
Committee
classified
Oxadiazon
as
a
Group
B2
­
probable
human
carcinogen,
and
recommended
that,
for
the
purpose
of
risk
characterization,
a
low
dose
extrapolation
model
be
applied
to
the
experimental
animal
tumor
data
for
quantification
of
human
risk
(
Q
1
*).
A
Q1*
based
upon
male
liver
(
carcinoma
and/
or
adenoma)
tumor
rates
was
generated
using
mg/
kg
b.
w.^
2/
3'
s/
day
cross
species
scaling
factor
(
Oxadiazon
hand­
written
memo,
B.
Fisher,
3/
16/
87).

This
revised
memo
has
been
generated
in
response
to
new,
more
appropriate
chronic/
oncogenicity
studies
submitted
to
the
Agency
and
to
reflect
the
Agency
policy
change
from
use
of
the
2/
3'
s
to
the
3/
4'
s
scaling
factor
in
1994
1.
Quantifications
of
risk
have
subsequently
2
been
estimated
for
these
new
studies.
The
most
potent
unit
risk
will
be
used
for
the
purpose
of
lifetime
cancer
risk
assessment
by
the
Agency.
In
this
case,
the
most
potent
unit
risk,
Q
1
*,
is
that
for
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
at
5.52
x
10­
2
in
human
equivalents.

All
unit
risks
have
been
converted
from
animals
to
humans
by
use
of
the
3/
4'
s
scaling
factor
(
Tox_
Risk
program,
Version
3.5,
K.
Crump,
1994)
1.
For
the
conversion
to
human
equivalents,
weights
of
0.03
kg
for
the
mouse,
0.35
kg
for
the
rat,
70
kg
for
humans,
the
use
of
98
weeks
for
the
mouse
life­
span
default
and
104
weeks
for
the
rat
lifespan
default
were
used.

It
is
to
be
noted
that
the
Q
1
*
(
mg/
kg/
day)­
1
is
an
estimate
of
the
upper
bound
on
risk
and
that,
as
stated
in
the
EPA
Risk
Assessment
Guidelines,
the
true
value
of
the
risk
is
unknown,
and
may
be
as
low
as
zero.

Dose­
Response
Analysis
There
were
no
significant
incremental
changes
in
mortality
with
increasing
doses
of
Oxadiazon
in
male
or
female
mice
or
rats
reported
in
the
studies.
The
unit
risks,
Q
1
*`
s,
were
obtained
by
the
application
of
the
Multi­
Stage
model
(
Tox_
Risk
program,
Version
3.5,
K.
Crump,
1994).

Male
mice
had
a
significant
increasing
trend
at
p
<
0.01,
and
significant
differences
in
the
pair­
wise
comparisons
of
the
100
(
p
<
0.05)
and
1000
(
p
<
0.01)
ppm
dose
groups
with
the
controls,
for
liver
adenomas
and/
or
carcinomas
combined.

Female
mice
had
a
significant
increasing
trend
at
p
<
0.01,
and
a
significant
difference
in
the
pair­
wise
comparison
of
the
1000
ppm
dose
group
with
the
controls
at
p
<
0.05,
for
liver
adenomas
and/
or
carcinomas
combined.
There
was
also
a
significant
difference
in
the
pair­
wise
comparison
of
the
1000
ppm
dose
group
with
the
controls
for
malignant
lymphomas
at
p
<
0.05.

Male
rats
had
a
significant
increasing
trend
at
p
<
0.01,
and
significant
differences
in
the
pair­
wise
comparisons
of
the
100
(
p
<
0.05)
and
1000
(
p
<
0.01)
ppm
dose
groups
with
the
controls,
for
liver
adenomas
and/
or
carcinomas
combined.

There
were
no
significant
trends
or
pair­
wise
comparisons
for
the
liver
tumors
of
female
rats.

Additional
Q
1
*
Calculations
The
unit
risk,
Q
1
*(
mg/
kg/
day)­
1,
of
Oxadiazon
based
upon
female
mouse
malignant
lymphoma
tumor
rates
is
2.89
x
10­
2
in
human
equivalents.
The
dose
levels
used
from
the
98­
week
dietary
study
were
0,
3,
10,
100,
and
1000
ppm
of
Oxadiazon.
The
corresponding
tumor
rates
were
16/
52,
25/
53,
19/
46,
21/
48,
and
27/
51,
respectively.
3
The
unit
risk,
Q
1
*(
mg/
kg/
day)­
1,
of
Oxadiazon
based
upon
female
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
is
1.31
x
10­
2
in
human
equivalents.
The
dose
levels
used
from
the
98­
week
dietary
study
were
0,
3,
10,
100,
and
1000
ppm
of
Oxadiazon.
The
corresponding
tumor
rates
were
1/
52,
0/
53,
0/
46,
1/
48,
and
7/
51,
respectively.

The
unit
risk,
Q
1
*(
mg/
kg/
day)­
1,
of
Oxadiazon
based
upon
male
rat
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
is
3.34
x
10­
2
in
human
equivalents.
The
dose
levels
used
from
the
104­
week
dietary
study
were
0,
3,
10,
100,
and
1000
ppm
of
Oxadiazon.
The
corresponding
tumor
rates
were
0/
53,
1/
55,
1/
54,
5/
54,
and
12/
52,
respectively.

The
unit
risk,
Q
1
*(
mg/
kg/
day)­
1,
of
Oxadiazon
based
upon
female
rat
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
is
8.16
x
10­
3
in
human
equivalents.
The
dose
levels
used
from
the
104­
week
dietary
study
were
0,
3,
10,
100,
and
1000
ppm
of
Oxadiazon.
The
corresponding
tumor
rates
were
1/
52,
1/
52,
1/
55,
1/
53,
and
3/
55,
respectively.
4
SignOff
Date:
1/
23/
01
DP
Barcode:
D000000
HED
DOC
Number:
014450
Toxicology
Branch:
SAB