Document ID: EPA-HQ-OPP-2005-0163-0038
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-05-17T04:00Z

Page
1
of
12
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
August
11,
2005
MEMORANDUM
SUBJECT:
Aldicarb.
List
A
Reregistration
Case
No.
0140/
Chemical
ID
No.
098301.
HED's
Response
to
Bayer
CropScience
"
Error
Only"
Comments.
DP
Barcode
No.
D320377.

FROM:
Felecia
Fort,
Chemist
Linda
L.
Taylor,
Ph.
D.,
Toxicologist
Jeff
Dawson,
Chemist
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

and
Jonathan
Angier,
Ph.
D
Environmental
Risk
Branch
2
Environmenatl
Fate
and
Effects
Division
(
7507C)

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

TO:
Mika
Hunter,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(
7508W)

Attached
is
the
Agency's
response
to
Phase
1
error
correction
comments
provided
by
the
registrant,
Bayer
CropScience
on
the
preliminary
human
health
risk
assessment
(
D299876/
June
20,
2005).
The
intent
of
this
document
is
to
illustrate
how
the
comments
were
considered
in
the
revisions
to
the
risk
assessment.
Each
comment
is
summarized
below
along
with
the
Agency
response
and
any
associated
changes
in
the
risk
assessment.
Page
2
of
12
Comments
to
the
"
HED
Preliminary
Human
Health
Risk
Assessment
for
the
Reregistration
Eligibility
Document"
dated
June
20,2005
Page
10
Paragraph
5
Lines
5­
7
EPA
Comment:
"
Short­
term
inhalation
MOEs
for
aldicarb
from
the
use
of
tobacco
are
estimated
to
be
80
for
females
and
90
for
males;
these
MOEs
are
greater
than
the
target
MOE
of
30,
.
.
."

Bayer
response:
The
MOEs
and
acceptable
MOE
target
of
30
are
inconsistent
with
the
risk
assessment
presented
on
page
36,
paragraph
5.
The
MOEs
for
females
and
males
are
presented
as
400
and
467
with
a
target
MOE
of
300.

Agency
response:
HED
concurs
and
will
make
the
changes
to
the
document.

Page:
18
Table
2
Row
5
EPA
Comment:
"
Acute
oral
study
(
human)
Inveresk",
"
42373001
(
1992)",
"
NOAEL
=
not
determined
for
females,
LOAEL
=
0.0
1
mg/
kg"

Bayer
response:
(
1):
Bayer
points
out
that
there
are
two
MRID
numbers
for
this
study
[
original
42373001;
supplementary
report
46131001].

Agency
response:
The
second
MRID
number
will
be
added
to
the
table.

Bayer
response:
(
2):
Bayer
disagrees
with
the
EPA
conclusion
that
a
NOAEL
was
not
determined
for
females
in
the
human
study;
the
LOAEL
is
listed
as
0.01
mg/
kg.

Agency
Reponse:
In
the
human
study
(
Inveresk)
study,
females
were
not
tested
at
the
lowest
dose
(
0.01
mg/
kg),
and
females
exhibited
more
plasma
and
RBC
cholinesterase
inhibition
than
the
males
at
the
two
common
dose
levels
[
0.025
mg/
kg
and
0.05
mg/
kg].
The
lack
of
dose­
response
information
for
females
at
the
low
dose
(
0.01
mg/
kg)
provides
uncertainty
for
this
study.
Bayer
is
correct
that
in
the
original
review
of
this
human
study
in
1992,
the
NOEL
was
determined
to
be
0.01
mg/
kg.
The
NOAEL
for
males
for
RBC
and
plasma
ChEI
and
clinical
signs
is
0.01
mg/
kg,
based
on
sweating
and
plasma
[
36%]
and
RBC
[
12%]
ChEI
at
0.025
mg/
kg.
Females
were
not
tested
at
0.01
mg/
kg,
and
the
magnitude
of
the
plasma
ChEI
[
at
0.025
mg/
kg
(
50%)]
and
RBC
ChEI
[
at
0.025
mg/
kg
(
20%)]
was
greater
in
females
than
males
at
the
two
common
dose
levels.
Because
of
this
uncertainty,
the
lowest
dose
tested
[
0.01
mg/
kg]
is
not
considered
an
overall
NOAEL
for
the
study.
Page
3
of
12
As
part
of
the
2005
human
health
risk
assessment
of
aldicarb,
a
re­
evaluation
of
the
full
database
of
toxicity
studies
on
aldicarb
was
performed,
which
included
the
human
study
referenced
above.
The
strengths
and
weaknesses
of
the
human
and
animal
toxicity
studies
were
compared,
which
included
an
assessment
of
whether
the
human
data
are
consistent
with
the
animal
data
in
terms
of
types
of
effects
and
effect
levels,
and
whether
there
are
notable
differences
between
animals
and
humans.

Page
32
Paragraph
5
EPA
Comment:
"
Surface
water
monitoring
data
for
aldicarb
and
its
metabolites
are
limited,
.
.
.
"

Bayer
response:
While
the
basis
of
the
surface
water
assessment
is
beyond
the
scope
of
error
corrections,
the
absence
of
any
mention
of
the
registrants
monitoring
program
of
drinking
water
from
surface
water
is
an
error.
Interim
results
of
this
study
were
presented
to
EPA
in
September
2001.
The
final
report
was
submitted
in
February
2005
and
was
assigned
MRID
Number
46466401.

Agency
response:
The
cited
document
(
MRID
#
46466401)
is
currently
being
reviewed
by
the
Environmental
Fate
and
Effects
Division
(
EFED).
Any
relevant
information
obtained
from
review
of
this
study
will
be
incorporated
into
subsequent
assessments/
corrections
(
where
applicable).

Page
34
Paragraph
2
Lines:
10­
11
EPA
Comment:
"
The
registrant
does
not
market
aldicarb
for
use
in
Northeastern
states."

Bayer
response:
Whether
or
not
to
sell
TEMIK
®
brand
Aldicarb
Pesticide
in
the
Northeastern
states
is
not
a
marketing
decision.
TEMIK
®
labels
prohibit
use
in
the
Northeastern
states
and
all
risk
assessments
should
accurately
reflect
this
fact.

Agency
response:
HED
concurs
and
will
make
the
appropriate
changes
to
the
document.

Page
35
Paragraph
1
Lines:
3­
6
EPA
Comment:
"
A
summary
of
the
suggested
ground
water
concentrations
for
use
in
the
drinking
water
exposure
assessment
has
been
taken
directly
from
the
EFED
RED
chapter,
and
is
presented
in
Table
6."

Bayer
response:
Although
Table
6
did
appear
in
the
preliminary
EFED
RED
chapter
dated
Page
4
of
12
June
2001,
this
table
is
not
in
the
EFED
Risk
Assessment
published
on
June
22,
2005.

Agency
response:
HED
concurs
and
will
make
the
appropriate
changes
to
the
document.

Page:
35
Table
6
EPA
Comment:
"
Table
6:
Suggested
Ground
Water
Concentrations
for
Use
in
the
Drinking
Water
Assessment."

Bayer
response:
If
EPA
is
going
to
include
a
table
to
represent
aldicarb
residues
in
ground
water,
it
should
either
cite
current
ground
water
residue
levels
or
thoroughly
explain
the
biases
included
in
the
table
(
i.
e.,
Table
6).
The
aldicarb
residue
concentrations
chosen
by
EPA
for
many
of
the
regions
are
not
appropriate.
Region
A:
This
was
an
analysis
from
a
bioassay
not
confmed
by
chemical
analysis.
Region
B:
This
was
a
detection
which
was
not
confirmed
in
follow­
up
sampling.
According
to
California
DPR,
follow­
up
sampling
showed
no
detectable
residues
for
all
four
of
the
detections
reported
to
them
by
the
California
Department
of
Health
Services
since
1992.
Region
C:
Residues
are
from
an
application
made
prior
to
the
1989
TEMIK
®
label
amendments
and
do
not
reflect
current
use.
Region
E:
As
TEMIK
®
cannot
be
used
in
Wisconsin,
the
residue
does
not
reflect
current
use.
The
selection
is
also
not
appropriate
for
other
states
in
the
regions,
because
in
addition
to
substantial
differences
in
soil
properties,
TEMIK
®
can
no
longer
be
applied
to
potatoes
in
this
region.
Region
F:
TEMIK
®
cannot
be
applied
in
any
state
in
thls
region
and,
with
the
exception
of
Long
Island,
residues
are
no
longer
present
in
ground
water.
Region
G:
The
detection
resulted
from
application
to
potatoes,
a
use
no
longer
permitted
in
Alabama.
The
principal
contributor
to
the
residue
was
an
improperly
sealed
well
with
open
space
between
the
casing
and
the
soil.
Region
H:
The
application
from
which
these
results
were
obtained
was
made
prior
to
the
Florida
best
management
practices
adopted
in
1994.

Agency
response
Region
A:
This
was
an
analysis
from
a
bioassay
not
confirmed
by
chemical
analysis.

Agency
response:
This
should
not
negate
the
validity
of
this
analysis.

Region
B:
This
was
a
detection
which
was
not
confirmed
in
follow­
up
sampling.
According
to
California
DPR,
follow­
up
sampling
showed
no
detectable
residues
for
all
four
of
the
detections
reported
to
them
by
the
California
Department
of
Health
Services
since
1992.

Agency
response:
It
is
not
uncommon
for
detections
to
occur
in
ground
water
at
one
time
and
not
occur
in
the
same
well
at
other
times.
Ground
water
is
not
static;
Page
5
of
12
although
it
typically
moves
much
more
slowly
than
surface
water,
the
chemical
characteristics
will
change
over
time
in
response
to
application
times,
rain
events,
irrigation,
etc.
Failure
to
detect
in
subsequent
samplings
does
not
invalidate
results
from
earlier
samples.

Region
C:
Residues
are
from
an
application
made
prior
to
the
1989
TEMIK
®
label
amendments
and
do
not
reflect
current
use.

Agency
response:
Specific
evidence
should
be
submitted
to
verify
that
this
detection
is
indeed
from
pre­
1989
usage
and
not
the
result
of
more
recent
use.
The
Agency
will
also
review
all
available
pertinent
monitoring
data
to
establish
whether
detects
result
from
pre­
1989
usage.

Region
E:
As
TEMIK
®
cannot
be
used
in
Wisconsin,
the
residue
does
not
reflect
current
use.
The
selection
is
also
not
appropriate
for
other
states
in
the
regions,
because
in
addition
to
substantial
differences
in
soil
properties,
TEMIK
®
can
no
longer
be
applied
to
potatoes
in
this
region.

Agency
response:
No
residues
are
expected
in
WI
because
aldicarb
is
no
longer
used.
Nevertheless,
although
it
is
banned
in
Wisconsin,
results
from
this
area
are
expected
to
reflect
the
impact
of
comparable
usage
in
other
areas
that
present
similar
soil/
aquifer
properties,
hydrologic
conditions,
and
climate.

Region
F:
TEMIK
®
cannot
be
applied
in
any
state
in
thls
region
and,
with
the
exception
of
Long
Island,
residues
are
no
longer
present
in
ground
water.

Agency
response:
No
residues
are
expected
in
this
region
because
aldicarb
is
no
longer
used,
however,
these
results
should
reflect
the
potential
long­
term
impact
of
comparable
usage
in
other
areas
that
present
similar
soil/
aquifer
properties,
hydrologic
conditions,
and
climate.

Region
G:
The
detection
resulted
from
application
to
potatoes,
a
use
no
longer
permitted
in
Alabama.
The
principal
contributor
to
the
residue
was
an
improperly
sealed
well
with
open
space
between
the
casing
and
the
soil.

Agency
response:
The
Agency
needs
certification
that
this
detection
resulted
from
potato
application.
Additionally,
need
additional
information
to
verify
that
the
putative
"...
improperly
sealed
well
with
open
space
between
the
casing
and
the
soil"
was
in
fact
the
primary
culprit
i.
e.,
how
was
this
determined?
The
Agency
will
also
review
currently
available
monitoring
information
to
assess
whether
origin
of
residues
can
be
determined.
Page
6
of
12
Region
H:
The
application
from
which
these
results
were
obtained
was
made
prior
to
the
Florida
best
management
practices
adopted
in
1994.

Agency
response:
The
Agency
concurs
that
there
are
more
recent
detects
from
post­
1994.
There
was
detection
in
Madison
County
in
1996
with
a
concentration
of
9.3
ppb.
This
value
will
be
used
for
this
Region
in
subsequent
drinking
water
assessments
later
in
the
public
participation
process.
However,
it
is
not
known
whether
the
seemingly
lower
concentrations
obtained
post­
1994
result
from
implementation
of
BMPs
or
the
installation
of
carbon
filters
on
ground
water
drinking
water
sources
that
had
previously
shown
detections.
There
are
shortcomings
to
the
body
of
monitoring
data
which
prevent
the
Agency
from
concluding
with
reasonable
certainty
that
label
changes
have
resulted
in
mitigations
that
lower
aldicarb
residues
to
concentrations
that
do
not
result
in
exposures
of
concern.
The
Agency
will
consider
any
studies
that
the
registrant
may
want
to
submit
to
quantitatively
support
mitigation
effects.

Page:
38
Table
7
Footnote
2
EPA
Comment:
"
Acute
Aggregate
Risk
=
%
of
the
aPAD,
or
0.0033mg/
kg/
day
=
[(
Total
Exposure/
0.00033
mg/
kg/
day)
x
100"

Bayer
response:
The
aPAD
is
inconsistent
with
that
quoted
in
the
text.
Additionally,
a
Footnote
5
is
referred
to
in
the
body
of
Table
7
but
not
found
in
the
footnote
section.

Agency
response:
HED
concurs
and
will
make
the
changes
to
the
document.

Page:
38
Table
8
EPA
Comment:
"
Table
8.
Aldicarb
Acute
Water
Exposure
and
Risk
for
Select
Population
Subgroups
at
the
95th
%
ile
of
Exposure."

Bayer
response:
The
title
of
Table
8
should
be,
"
Aldicarb
Acute
Water
Exposure
and
Risk
for
Select
Population
Subgroups
at
the
99.9"
%
ile
of
Exposure."

Agency
response:
HED
concurs
and
will
make
the
changes
to
the
document.

Page:
43
Paragraph
1:
Lines:
5­
6
EPA
Comment:
"
HED
has
recommended
that
labels
specify
the
default
Worker
Protection
Standard
re­
entry
(
REI),
which
is
determined
based
on
the
acute
toxicity
of
the
active
ingredient."
Page
7
of
12
Bayer
response:
TEMIK
®
labels
do
specify
an
RE1
of
48
hours,
which
is
based
on
the
dermal
acute
toxicity
of
the
active
ingredient.
As
per
the
Worker
Protection
Standard,
the
labels
also
contain
an
exception
to
the
RE1
for
noncontact
activities
following
soil
incorporation.
The
wording
in
the
preliminary
risk
assessment
suggests
that
TEMIK
®

labels
do
not
currently
have
the
48­
hour
REI.
A
sentence
should
be
added
stating
that
the
HED
recommendation
is
consistent
with
current
labeling.

Agency
response:
HED
concurs
and
will
make
the
changes
to
the
document.

Error
Corrections
to
the
Document:
"
Revised
Anticipated
Residues
and
Dietary
Exposure
Analyses"
Dated
June
20,2005,
196
pages
Page:
7
Paragraph:
6
Lines:
1­
2
EPA
Comment:
"
The
HED
selected
doses
and
endpoints
for
the
human
health
risk
assessment
for
aldicarb
(
L.
Taylor,
5//
05,
TXR
No.
xxxxx)."

Bayer
response:
The
appropriate
date
and
reference
number
for
this
document
should
be
filled
in.

Agency
response:
HED
concurs
and
will
make
the
changes
to
the
document.
The
referenced
document
is
"
Weight
of
Evidence
Comparison
of
Human
and
Animal
Toxicology
Studies
and
Endpoints
for
ALDICARB
[
PC
Code
098301;
DP
Barcode:
D299876]"
is
dated
June
28,
2005
[
TXR#
0053495].

Page:
12
Paragraph:
2
Lines:
1­
2
EPA
Comment:
"
Overviews
of
the
PDP
(
1994­
1998)
and
FDA
data
(
1992­
1998)
for
aldicarb
are
shown
in
Tables
3
and
4,
respectively."

Bayer
response:
The
overviews
"
are
shown
in
Tables
4
and
5,
respectively."

Agency
response:
HED
concurs
and
will
make
the
changes
to
the
document.

Page:
97
Lines:
43­
50
EPA
Comment:
In
the
residue
file,
Adj.
Factor
#
1
for
Grapefruit,
juice
is
entered
as
0.014.

Bayer
response:
The
correct
Grapehit
juice
Adj.
Factor
#
1
is
0.14.
Page
8
of
12
Agency
response:
HED
concurs
with
the
registrant.
Revising
the
dietary
assessment
results
in
negligible
changes
to
the
exposure
and
risk
estimates
(<
0.5%);
therefore,
HED
will
not
make
the
corrections
at
this
time.
The
changes
will
be
made
during
Phase
4
of
the
reregistration
process.

Error
Corrections
to
the
Document:
"
Revised
Occupational
and
Residential
Exposure
and
Risk
Assessment"
Dated
January
11,
2005,
33
pages
General
Agency
response:
The
Occupational
and
Residential
Exposure
Assessment
for
the
Aldicarb
Reregistration
Eligibility
Decision
was
completed
prior
to
the
preliminary
Human
Health
Assessment.
Although
the
Human
Health
Assessment
was
updated
with
new
endpoints,
the
ORE
chapter
has
not
been
updated,
nor
will
it
be
at
this
time.
The
risk
estimates
do
not
correspond
to
the
current
endpoints;
however,
the
exposure
scenarios
and
exposure
levels
represented
in
the
chapter
are
accurate.
The
errors
noted
by
the
registrant,
Bayer
CropScience,
if
appropriate,
will
be
corrected
at
a
later
point
in
the
public
participation
process.

General
Comment
EPA
Comment:
At
various
points,
the
occupational
risk
assessment
discusses
or
uses
the
term
"
mixer/
loaders".

Bayer
response:
Because
TEMIK
®
is
a
granular
product
there
is
no
mixing
involved
in
handling.
The
assessment
should
refer
to
"
loaders"
rather
than
"
mixer/
loaders"
as
the
more
correct
term.
The
Agency
assessment
does
use
the
term
"
loader"
in
addition
to
"
mixer/
loader.
This
correction
would
also
provide
consistency.

Agency
response:
HED
concurs
with
the
registrant
.

Page:
5
Paragraph
4:
Line:
8
EPA
Comment:
".
.
.
observed
at
the
LOAEL
(
0.25
mg/
kg/
day)."

Bayer
response:
The
human
study
had
a
dose
level
of
0.025
mg/
kg/
day,
not
0.25
mg/
kg/
day.
Page
9
of
12
Agency
response:
The
registrant
is
correct
in
that
the
dose
level
in
the
human
study
is
0.025
mg/
kg/
day
and
not
0.25
mg/
kg/
day.
However,
the
referenced
document
[
dated
1/
11/
2005]
was
completed
prior
to
the
completion
of
the
2005
Weight
of
Evidence
Comparison,
in
which
it
was
determined
that
the
dose
level
of
0.01
mg/
kg
is
the
LOAEL
since,
as
noted
above,
the
latter
dose
level
was
not
tested
in
females.
The
Revised
ORE
document
was
not
further
revised
after
January,
2005
to
include
this
change.

Page:
9
Paragraph
3
Bullet:
1
Lines:
3­
4
EPA
Comment:
".
.
.
(
FL
specifies
use
of
5
lb
ai/
acre
to
apply
between
January
1
and
April
30
only,
no
limit
to
number
of
applications
is
specified)."

Bayer
response:
The
assessment
appears
to
address
EPA
SLN
No.
FL­
880003.
This
label
refers
the
user
to
the
Federal
TEMIK
®
brand
15G
label
for
further
instructions
and
information.
The
TEMIK
®
15G
label
states,
"
Do
not
exceed
33
pounds
per
acre
for
all
applications
to
citrus."
Therefore,
the
EPA
comment
regarding
no
limit
to
the
number
of
applications
to
citrus
in
Florida
in
incorrect.

Agency
response:
The
wording
in
the
assessment
will
be
changed
later
in
public
participation
process.

Page:
9
Paragraph
3
Bullet:
2
Lines:
1­
3
EPA
Comment:
"
Field,
Forage,
and
Fiber
Crops:
Application
rates
range
from
1
to
5
lb
ai
per
acre
once
per
year.
.
."

Bayer
response:
The
minimum
application
rate
of
1
lb
ai/
A
(
6.7
lb
formulation/
acre)
is
incorrect.
There
are
a
variety
of
recommended
application
rates
on
the
TEMIK
®
label
that
are
less
than
1
lb
ai/
A.
The
lowest
recommended
rate
is
0.3
lb
ai/
A
(
2
lb
formulatiodacre)
for
aphids
and
thnps
control
on
cotton
in
Texas,
Oklahoma,
and
New
Mexico.
A
rate
of
0.525
lb
ai/
A
(
3.5
lb
formulatiodacre)
is
provided
on
the
label
for
aphids
and
thrips
control
in
other
states.

Agency
response:
The
wording
in
the
assessment
will
be
changed
later
in
public
participation
process.

Page:
12
Bullet:
1
Lines:
1­
2
EPA
Comment:
"
Average
body
weight
of
an
adult
handler
is
70
kg
because
the
LOAEL
used
for
the
.
.
."
Page
10
of
12
Bayer
response:
LOAEL
should
be
NOAEL.
This
is
consistent
with
Table
1,
Endpoints
for
Assessing
Occupational
Risks
for
Aldicarb.

Agency
response:
The
wording
in
the
assessment
will
be
changed
later
in
public
participation
process.
.

Error
Corrections
to
the
Document:"
Toxicology
Chapter
for
Aldicarb"
Dated
August
20,2002,
38
pages
General
Agency
response:
The
Toxicology
Chapter
on
Aldicarb
was
completed
in
2002,
and
no
revision
was
generated
to
incorporate
the
2005
deliberations
and
revised
risk
assessment.
The
procedures
in
effect
currently
in
the
risk
assessment
process
do
not
include
a
revision
to
the
toxicology
chapter.
Currently,
no
separate
Toxicology
Chapter
is
generated;
the
Hazard
Characterization/
Assessment
section
of
the
Risk
Assessment
Document
replaces
the
toxicology
chapter
and
HIARC
document.
All
toxicological
aspects
are
incorporated
directly
into
the
risk
assessment
document.
The
2002
Toxicology
Chapter
should
be
considered
as
background
information,
and
the
4.0
Hazard
Characterization/
Assessment
section
of
the
Risk
Assessment
Document
provides
the
revised
toxicology
analysis
for
aldicarb.

Page
8
870.3150
90­
day
Oral
Toxicity
­
Dog
EPA
conclusions:
Executive
Summary
of
study
Bayer
response:
"
According
to
the
study
report,
a
NOEL
based
on
erythrocyte
cholinesterase
was
established
at
2
ppm
(
equal
to
0.06
mg/
kg
bw/
day)
and
the
NOEL
for
any
symptoms
including
plasma
cholinesterase
depression
was
0.7
ppm
(
equal
to
0.02
mg/
kg
bw/
day)."

Agency
response:
In
it's
review
of
this
study,
HED
concluded
that
the
NOAEL
for
plasma
and
RBC
cholinesterase
inhibition
was
0.02
mg/
kg/
day,
and
the
LOAEL
was
0.06
mg/
kg/
day.
It
is
to
be
noted
that
this
5­
week
study
was
conducted
to
establish
an
NOAEL
for
blood
cholinesterase
inhibition
since
a
NOAEL
had
not
been
determined
in
the
chronic
dog
study.
The
data
were
consistent
with
the
finding
of
similar
response
for
cholinesterase
inhibition
in
the
rat
and
human
[
effect
level
of
0.05
mg/
kg/
day].
Page
11
of
12
Page
11
870.400b
Chronic
Toxicity
­
Dog
EPA
conclusions:
Executive
Summary
of
study
Bayer
response:
Aldicarb
at
up
to
20
ppm
(
equal
to
0.241
mg/
kg
bw/
day)
caused
no
observable
effects
other
than
inhibition
of
cholinesterase
activity.
Inhibition
of
erythrocyte
and
brain
cholinesterase
activity
was
restricted
to
dogs
receiving
5
or
10
ppm.
The
NOEL
for
plasma
cholinesterase
inhibition
was
1
ppm,
equl
to
0.027
mg/
kg
bw/
day.
The
NOEL
for
erythrocyte
cholinesterase
inhibition
was
2
ppm,
equal
to
0.054
mg/
kg
bw/
day.

Agency
response:
As
described
above,
a
NOAEL
was
not
determined
in
the
dog
chronic
study,
based
on
the
finding
of
a
significant
plasma
cholinesterase
inhibition
in
males
[
21%­
28%]
at
the
lowest
dose
[
0.028
mg/
kg/
day].
It
is
to
be
noted
that
a
dose
of
0.025
mg/
kg
tested
in
the
human
study
was
also
an
effect
level
and
is
similar
to
0.028
mg/
kg/
day.

Page
14
870.3700
Prenatal
Developmental
Toxicity
Study
­
Rat
EPA
Comment:
Developmental
NOAEL
=
0.125
mg/
kg/
day."

Bayer
response:
The
NOEL
was
0.125
mg/
kg
bw/
day
for
maternal
toxicity
and
0.25
mg/
kg
bw/
day
for
embryo
fetal
toxicity
and
teratogenicity.

Agency
response:
The
basis
for
the
selection
of
0.125
mg/
kg/
day
as
the
NOAEL
was
the
incidence
of
ecchymosis
of
the
trunk
(
small
blood
stained
areas
under
the
skin)
at
the
0.25
mg/
kg/
day
dose
level,
which
was
considered
an
effect.

Pages
16
and
17
870.6200
Acute
Neurotoxicity
Screening
Battery
EPA
Comment:
"
The
NOAEL
is
<
0.05
mg/
kg.
The
LOAEL
is
0.05
mg/
kg,
based
on
decreased
whole
blood
and
plasma
ChEI.
The
NOAEL
for
brain
ChEI
is
0.05
mg/
kg,
and
the
LOAEL
for
brain
ChEI
is
0.1
mg/
kg.

Bayer
response:
The
NOEL
for
the
FOB
and
motor
activity
evaluations
was
0.1
mg/
kg
for
both
sexes.
The
NOEL
for
periphral
cholinesterase
measurements
was
0.05
mg/
kg.
The
NOEL
for
brain
cholinesterase
was
0.1
mg/
kg.
The
observed
NOEL
for
neuropathology
findings
was
0.5
mg/
kg,
the
highest
dose
tested
in
the
study.

Agency
response:
The
NOEL
for
neuropathology
[
0.5
mg/
kg]
is
consistent
with
the
HED
conclusion
that
no
neuropathological
changes
were
observed.
Although
not
statistically
significant,
the
magnitude
of
the
brain
cholinesterase
inhibition
at
0.1
mg/
kg
[
females
16%]
was
considered
treatment­
related.
Additionally,
especially
for
females,
the
magnitude
of
the
cholinesterase
inhibition
observed
at
0.05
mg/
kg
leads
to
the
conclusion
that
this
dose
level
is
the
LOAEL.
This
2002
determination
was
confirmed
in
the
2005
weight
of
evidence
assessment.
Page
12
of
12
Page
36
Table
8.2
column
2
Rows
2­
3
EPA
Comment:
"
Acute
RfD
=
0.00005
mg/
kg/
day"
and
"
Chronic
RfD
=
0.00005
mg/
kg/
day"
and
"
UF
=
1000"

Bayer
response:
The
RfDs
and
UF
of
1000
are
not
consistent
with
the
RfDs
and
UF
stated
"
in
other
parts
of
the
document
(
including
the
executive
summary)".
In
additiion,
this
error
occurs
in
several
places
in
Table
8.2.

Agency
response:
It
is
reiterated
that
the
Toxicology
Chapter
was
finalized
in
2002
and,
as
discussed
above,
it
was
not
revised.
These
cited
RfDs
and
UF
reflect
the
HED
assessment
of
the
data
at
that
time
[
2002].
It
is
not
clear
what
document
is
being
referred
to:
not
consistent
with
the
RfDs
and
UF
stated
"
in
other
parts
of
the
document
(
including
the
executive
summary)".
If
the
document
is
the
HED
Preliminary
Human
Health
Risk
Assessment
of
the
RED,
then
the
above
explanation
addresses
this
comment.