Document ID: EPA-HQ-OPP-2003-0294-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-09-04T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
WASHINGTON,
D.
C.
20460
MEMORANDUM
DATE:
August
12,
2003
SUBJECT:
Lactofen.
Revisions
to
HED
Tolerance
Reassessment
Risk
Assessment.
DP
Barcode:
D292794
PC
Code:
128888
FROM:
Michael
S.
Metzger,
Chief.
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

THRU:
Whang
Phang,
Ph.
D.,
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

To:
Christina
Scheltema,
Chemical
Review
Manager
Michael
Goodis,
Acting
Branch
Chief
Reregistration
Branch
3
Special
Review
and
Reregistration
Division
(
7508C)

Introduction:

This
memo
updates
the
HED
Chapter
for
the
Reregistration
Eligibility
Decision
Document
for
lactofen
(
D269621,
October
12,
2000).
The
only
changes
to
the
risk
assessment
are
new
cancer
risk
estimates
based
on
the
new
cancer
classifications
of
lactofen
and
its
metabolite
acifluorofen.
As
described
below,
there
are
no
cancer
concerns
from
lactofen
or
acifluorfen
exposure
by
any
route
or
pathway.

The
cancer
classification
for
lactofen
was
changed
after
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(
MTARC)
reviewed
new
data
and
concluded
that
peroxisome
proliferation
was
supported
as
the
mode
of
action
of
lactofen­
induced
liver
tumors
in
rodents.
The
MTARC
(
TXR
014590,
March
12,
2001
report)
evaluated
the
data
according
to
criteria
from
the
International
Life
Sciences
Institute.
The
Cancer
Assessment
Review
Committee
reclassified
lactofen
in
light
of
these
new
data
(
TXR
0050184,
May
21,
2002
report),
and
the
conclusions
of
the
MTARC.
Discussion:

The
previous
cancer
classification
of
lactofen
was
"
Group
B2,
probable
human
carcinogen",
cancer
risk
was
assessed
using
a
Q
1*.

The
present
cancer
classification
is
"
likely
to
be
carcinogenic
to
humans
at
high
enough
doses
to
cause
these
biochemical
and
histopathological
effects
in
livers
of
rodents
but
unlikely
to
be
carcinogenic
at
doses
below
those
causing
these
changes".
Human
cancer
risk
is
now
assessed
by
a
margin
of
exposure
(
MOE)
approach,
using
a
NOAEL
=
0.3
mg/
kgbw/
day
and
margin
of
exposure
of
100.
A
cancer
risk
assessment
is
required
only
for
chronic
or
long
term
exposures.

The
revised
dietary
cancer
risk
estimate
for
the
U.
S.
general
population
for
lactofen
is
summarized
below.
The
exposure
level
used
was
that
previously
employed
for
the
chronic
dietary
risk
assessment
for
lactofen.

Cancer
MOE
=
NOAEL
=
0.3
mg/
kgbw/
day
=
300,000
Exposure
1x10­
6
mg/
kgbw/
day
Since
the
estimated
dietary
cancer
risk
is
well
above
the
target
MOE
=
100,
there
are
no
concerns
for
cancer
risk
from
chronic
exposure
to
lactofen
in
food.

The
following
table
summarizes
drinking
water
cancer
risks
for
lactofen.

Cancer
NOAEL
(
mg/
kgbw/
day)
Target
MOE
Target
exposure
(
mg/
kgbw/
day)
Food
+
residential
exposure
(
mg/
kgbw/
day)
Max
drinking
water
exposure
(
mg/
kgbw/
day)
EEC
­
PRZM/
EXAMS
(
ug/
L)
EEC
­
SCI­
GROW
(
ug/
L)
DWLOC
(
ug/
L)

0.3
100
0.003
1x10­
6
0.003
0.022
0.006
105
Since
the
Estimated
Environmental
Concentrations
(
EECs)
are
well
below
the
Drinking
Water
Level
of
Comparison
(
DWLOC),
cancer
risks
from
lactofen
in
drinking
water
are
not
of
concern.

There
are
no
concerns
from
chronic
residential
or
occupational
exposure
because
chronic
exposure
by
these
pathways
is
not
expected.

Dietary
drinking
water
risks
from
acifluorofen
resulting
from
lactofen
applications
were
discussed
in
the
review
of
Kit
Farwell,
D.
V.
M.
(
7/
14/
03).
The
assessment
considered
the
recent
cancer
reclassification
of
acifluorofen
as
a
peroxisome
proliferator
with
risk
quantification
using
an
MOE
approach.
The
following
was
concluded:

Cancer
risks
from
drinking
water
exposure
were
evaluated
both
from
exposure
to
the
herbicide,
sodium
acifluorfen,
and
from
exposure
to
acifluorfen
as
a
degradate
of
the
herbicide,
lactofen.
There
were
no
concerns
for
cancer
risk
by
exposure
from
either
source
because
the
drinking
water
level
of
comparison
(
DWLOC)
for
chronic
exposure
was
greater
than
estimated
drinking
water
concentrations
(
EDWCs)
for
acifluorfen
from
either
source.
Please
refer
to
that
review
for
further
information
regarding
acifluorofen
resulting
from
lactofen
applications.

Acifluorofen
is
not
considered
a
significant
metabolite
of
lactofen
in
foods,
so
acifluorofen
risks
from
this
source
are
not
expected.

Conclusions:

There
are
no
cancer
concerns
from
lactofen
or
acifluorfen
exposure
by
any
route
or
pathway.
This
risk
assessment
update
can
be
used
to
support
the
Tolerance
Reassessment
decision
as
well
as
the
new
uses
and
tolerances
for
cotton
and
peanuts.
Although
the
assessment
is
based
on
use
of
a
3X
FQPA
safety
factor
for
a
missing
rabbit
developmental
study
(
applied
only
to
the
acute
dietary
assessment
for
females
13­
50),
aggregate
risks
would
still
be
acceptable
even
if
a
10X
factor
were
applied,
since
the
dietary
food
risk
is
<
0.1%
of
the
aPAD,
and
the
acute
DWLOC
is
over
1000­
fold
greater
than
the
highest
EEC.

BIBLIOGRAPHY
Mechanism
of
Toxicity
SARC
Report:
Lactofen
(
PC
Code:
128888).
Robert
F.
Fricke,
March
12,
2001.
TXR
No.
014590.

Cancer
Assessment
Document:
Evaluation
f
the
Carcinogenic
Potential
of
Lactofen
(
Second
Review)
Cancer
Assessment
review
Committee
may
21,
2002.
TXR
No.:
0050184
Lactofen:
Preliminary
Human
Health
Risk
Assessment
for
Tolerance
reassessment
Incorporating
Revised
Cancer
Unit
Risks
Christine
L.
Olinger,
October
12,
2000
Sodium
Acifluorofen.
Revision
to
the
HED
Chapter
for
the
Reregistration
Eligibility
Document
Kit
Farwell,
D.
V.
M.,
July
14,
2003