Document ID: EPA-HQ-OPP-2005-0227-0027
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-29T05:00Z

Page
1
of
5
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
March
8,
2006
MEMORANDUM
SUBJECT:
Phase
4:
Response
to
Public
Comments
for
the
Acetochlor
TRED.
PC
Code:
121601,
DP
Barcode:
D292335.

FROM:
Alberto
Protzel,
Ph.
D.,
Branch
Senior
Scientist
and
Risk
Assessor
Toxicology
Branch
Health
Effects
Division
(
7509C)
AND
Linnea
Hansen,
Ph.
D.,
Toxicologist
Toxicology
Branch
Health
Effects
Division
(
7509C)
AND
Samuel
Ary,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(
7509C)

THROUGH:
Louis
Scarano,
Ph.
D.,
Chief
Toxicology
Branch
Health
Effects
Division
(
7509C)

TO:
Felicia
Fort,
Chemical
Review
Manager
Reregistration
Branch
III
Special
Review
and
Reregistration
Division
(
7508W)

Introduction
The
Health
Effects
Division
(
HED)
of
the
Environmental
Protection
Agency
(
EPA)
has
reviewed
public
comments
submitted
by
the
Acetochlor
Registration
Partnership
(
ARP)
Page
2
of
5
on
the
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document
for
acetochlor.
Public
comments
were
addressed
by
Alberto
Protzel,
Linnea
Hansen,
Samuel
Ary,
Michael
Barrett
and
Ronald
Parker.

The
ARP
comments
were
received
as
four
attachments
covering
specific
areas
of
concern
in
the
Acetochlor
TRED:

Attachment
1:
Analytical
Chemistry
and
Residue
Data
Attachment
2:
Product
Chemistry
Attachment
3:
Toxicology
and
Human
Risk
Assessment
Attachment
4:
Drinking
Water
Exposure
Assessment.

This
document
contains
HED's
responses
to
comments
submitted
by
the
ARP
in
Attachments
1,
2,
and
3.
The
ARP
comments
in
Attachment
4
will
be
addressed
by
the
Environmental
Fate
and
Effects
Division
(
EFED)
in
a
separate
document.

ARP
Comments
and
HED's
Responses
to
the
Comments
Attachment
1.
ARP
Comments
on
Analytical
Chemistry
and
Residue
Data
Comment
1:
In
the
dietary
exposure
assessment
for
the
acetochlor
TRED,
DP
Barcode
D297061,
S.
Ary
suggested
that
an
interim
tolerance
of
2.0
ppm
be
set
for
wheat
hay
based
on
the
maximum
residues
of
0.457
ppm
in
wheat
forage
corrected
for
moisture
content.
The
ARP
respectfully
suggests
that
this
approach
may
be
suitable
for
setting
tolerances
for
wheat
hay,
in
lieu
of
requiring
the
repeat
of
extensive
two
year
trials.

Agency's
Response:
It
has
been
determined
that
a
permanent
tolerance
of
2.0
ppm
be
set
for
wheat
hay
based
on
the
maximum
residues
of
0.457
ppm
in
wheat
forage
corrected
for
moisture
content.
HED,
in
agreement
with
the
ARP,
feels
this
does
represent
a
worst­
case
residue
given
that
the
calculated
hay
tolerance
is
based
on
the
maximum
forage
residue,
and
growth
dilution
is
expected
between
the
forage
and
hay
harvest
stage.
Additionally,
wheat
hay
is
not
considered
a
significant
livestock
feed
item
in
comparison
to
corn
and
therefore
was
not
considered
in
calculating
the
theoretical
livestock
dietary
burden
from
acetochlor.

Comment
2:
The
ARP
respectfully
requests
that
the
pop
corn
use
remain
on
the
acetochlor
labeling
conditioned
on
the
formal
submission
of
a
tolerance
petition
which
would
rely
on
the
existing
data
for
field
corn
with
no
additional
data
supplied
or
required.

Agency's
Response:
Since
this
assessment
is
a
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
and
new
uses
are
not
being
considered,
the
Registration
Division
will
consider
the
request
by
the
ARP
to
establish
a
tolerance
for
pop
corn
using
the
Page
3
of
5
available
field
corn
magnitude
of
residue
data.

Attachment
2.
ARP
Comments
on
Product
Chemistry
Requirements
Comment
1:
The
ARP
notes
that
most
of
these
requirements
have
already
been
met
in
a
report
submitted
previously
and
referenced
in
this
memo.

Agency's
Response:
The
product
chemistry
requirements
have
been
met
for
stability,
oxidation/
reduction,
flammability,
explodability,
miscibility,
and
viscosity
(
OPPTS
830.6313,
6314,
6315,
6316,
6319,
and
7100)
as
submitted
in
MRID
40994402.
HED
will
be
awaiting
the
UV­
Visible
absorption
study
as
required
by
OPPTS
830.7050.

Attachment
3:
ARP
Comments
on
Toxicology
and
Human
Risk
Assessment
Topic
1:
Carcinogenicity
of
Acetochlor:

The
ARP
disagreed
with
the
Agency's
identification
of
treatment­
related
tumors
(
1)
lung
and
(
2)
histiocytic
sarcoma,
(
3)
cancer
classification
and
(
4)
quantification
of
cancer
risk
for
acetochlor.
Comments
on
each
point
of
disagreement
are
summarized
below.
A
review
of
each
of
these
issues
by
the
EPA
Scientific
Advisory
Panel
(
SAP)
was
also
requested.

(
1)
ARP
Comments
on
Lung
tumors
in
mice:
The
ARP
considered
the
lung
tumors
observed
in
mice
to
be
unrelated
to
treatment
with
acetochlor.
Their
conclusion
was
based
on
the
pathology
working
group
(
PWG)
peer
review
reevaluation
of
these
tumors
(
MRID
44496206),
which
concluded
that
the
tumors
were
within
normal
variation.
Because
they
are
common
tumors,
the
ARP
did
not
support
the
use
of
statistical
significance
at
p<
0.05
to
confer
biological
significance.
The
PWG
also
concluded
that
these
tumors
did
not
show
a
linear
dose­
response
and
lacked
tumor
multiplicity
with
increasing
dose.
The
ARP
cited
the
European
Chemical
Bureau
reports
of
1997
and
1998,
which
determined
that
acetochlor
did
not
appear
to
produce
treatment­
related
tumors.
It
was
noted
as
well
that
the
EPA
consulting
pathologist,
Dr.
J.
Pletcher,
did
not
find
fault
with
the
PWG
conclusions,
that
a
positive
dose­
response
was
not
observed
in
males
in
the
two­
year
study
at
the
highest
doses
tested
(
1500
ppm
and
5000
ppm)
and
that
the
tumor
response
in
males
in
the
18­
month
study
was
not
strongly
statistically
significant
(
at
p<
0.05
level).
In
females,
only
a
positive
trend
was
seen
in
the
18­
month
study,
an
increase
that
the
ARP
did
not
consider
to
be
biologically
significant.
Lung
tumor
incidence
was
stated
to
be
comparable
to
historical
control
values,
when
considering
the
relatively
low
concurrent
control
incidence
and
when
considering
the
Agency's
adjusted
tumor
incidence
(
exclusion
of
animals
that
died
before
first
tumor
observation).
Mortality
at
1500
and
5000
ppm
in
females,
the
doses
at
which
the
highest
lung
tumor
incidences
were
observed,
was
noted
to
be
high
(
66%
and
74%,
respectively).
Page
4
of
5
(
2)
ARP
Comments
on
Histiocytic
sarcoma
in
female
mice:
The
ARP
stated
that
they
believe
"...
that
there
is
insufficient
evidence
for
the
Agency
to
conclude
that
the
slightly
increased
incidence
of
histiocytic
sarcomas
in
female
mice
was
definitively
related
to
treatment."
Their
conclusion
was
based
on
an
"
unusually
low"
concurrent
control
value
for
the
2­
year
study
(
0%),
increased
mortality
of
females
at
1500
and
5000
ppm
in
females
(
control
to
high
dose
)
and
common/
variable
occurrence
of
histiocytic
sarcoma
in
older
female
mice.
The
ARP
also
cited
the
PWG
peer
review
of
histiocytic
sarcoma
in
mice
(
MRID
44496204)
and
the
Agency's
consulting
pathologist
(
J.
Pletcher),
which
concluded
that
these
tumors
were
probably
not
treatment­
related,
as
did
the
European
Chemical
Bureau
reports
of
1997
and
1998.

(
3)
ARP
Comments
on
Cancer
classification
of
acetochlor:
Based
on
the
issues
as
outlined
above,
lack
of
data
supporting
a
genotoxic
mode
of
action
and
the
non­
linear
mode
of
action
assigned
to
the
nasal
and
thyroid
tumors,
the
ARP
considered
the
cancer
data
on
acetochlor
to
be
supportive
of
a
cancer
classification
of
"
suggestive
evidence
of
carcinogenic
potential."

(
4)
ARP
Comments
on
Quantitative
Risk
Assessment:
The
ARP
considered
use
of
linear
low­
dose
extrapolation
and
assignment
of
a
Q*
for
cancer
risk
assessment
of
acetochlor
to
be
inappropriate,
due
to
lack
of
apparent
genotoxic
mode
of
action
and
use
of
the
lung
tumors
as
the
basis
for
quantitation
of
risk.

Agency
Response:
The
Agency
has
reviewed
the
comments
provided
by
the
ARP
regarding
carcinogenicity
of
acetochlor.
The
Agency
will
reevaluate
the
carcinogenicity
of
acetochlor,
with
consideration
of
these
comments,
through
the
HED
Cancer
Assessment
Review
Committee
(
CARC).
A
request
for
a
review
by
the
EPA
SAP
will
not
be
submitted
at
this
time.

Topic
2:
Request
for
a
Developmental
Neurotoxicity
Study:

ARP
Comments:
The
ARP
asked
the
Agency
to
reconsider
the
request
for
a
developmental
neurotoxicity
study,
based
on
(
1)
neurotoxic
effects
observed
only
at
high
doses
in
adult
animals,
(
2)
no
evidence
of
neurotoxicity
nor
increased
susceptibility
in
developmental
or
reproductive
toxicity
studies,
(
3)
no
clear
evidence
of
direct
or
specific
neurotoxicity
in
the
acute/
subchronic
neurotoxicity
screening
studies
and
(
4)
unlikely
impact
on
the
risk
assessment.

Agency
Response:
The
HED
RARC
based
the
decision
to
require
this
study
on
findings
of
neurotoxicity
in
two
species
and
frank
neuropathology
with
associated
clinical
effects
in
the
dog.
The
available
developmental
and
reproductive
toxicity
studies,
while
not
indicating
evidence
of
neurotoxicity,
may
not
detect
more
subtle
neurotoxic
effects
on
the
fetus.
The
developmental
neurotoxicity
study
requirement
will
be
retained
to
better
assess
whether
effects
may
occur
during
development.
Page
5
of
5
Topic
3:
Environmental
Degradates
ARP
Comment:
The
ARP
requests
that
the
Agency
establish
chronic
RfDs
for
the
ESA
and
OXA
degradates
of
acetochlor,
as
well
as
for
the
corresponding
ESA
degradate
for
alachlor.
HED
has
concluded
that
there
is
a
substantial
margin
of
exposure
for
all
three
of
these
degradates
and
that
the
low
levels
detected
in
drinking
water
does
not
pose
a
significant
risk
to
human
health
and
is
thus
not
of
concern.
However,
the
Agency
has
not
explicitly
defined
what
level
of
humane
exposure
to
these
should
be
considered
safe.

Agency
Response:
The
Agency
has
reviewed
the
comments
provided
by
the
ARP
regarding
the
establishing
of
chronic
RfDs
for
the
ESA
and
OXA
degradates
of
acetochlor,
as
well
as
for
the
corresponding
ESA
degradate
for
alachlor.
The
Agency
will
address
the
issue
of
establishing
RfDs
for
the
cited
water
degradates,
with
consideration
of
the
ARP
comments,
through
the
HED
RARC
Committee
or
a
similarly
suitable
ad
hoc
committee.

Topic
4.
Presence
of
Acetochlor
in
Breast
Milk:

ARP
Comment:
On
p.
31
of
the
TRED,
the
Agency
stated
that
reduced
pup
weight
"
indicated
that
acetochlor
and/
or
its
metabolites
are
present
in
breast
milk."
The
ARP
noted
that
the
reduced
pup
weight
may
have
been
due
to
other
factors
and
requested
removal
of
the
statement.

Agency
Response:
The
Agency
agreed
with
the
ARP
and
has
removed
the
statement
from
the
TRED.