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ATTACHMENT
1
Issues
for
February,
2005
FIFRA
Scientific
Advisory
Panel
Meeting
Similar
to
the
scientific
peer
process
followed
for
the
Cumulative
Risk
Assessment
(
CRA)
for
the
Organophosphorus
Pesticides
(
OPs),
OPP
plans
to
consult
with
the
FIFRA
Science
Advisory
Panel
(
SAP)
to
seek
expert
review,
advice,
and
recommendations
at
each
major
step
in
development
of
the
CRA
for
the
N­
methyl
carbamates.
The
following
text
describes
the
general
framework
being
considered
by
EPA
as
it
develops
its
CRA
for
the
N­
methyl
carbamate
pesticides
focusing
on
the
SAP
meeting
scheduled
for
mid­
February.
This
framework
is
meant
to
provide
the
SAP
members
along
with
the
public
with
an
overview
of
the
various
aspects
of
the
assessment.

February
15­
18,
2005:
FIFRA
SAP
Meeting:
N­
methyl
carbamate
pesticide
cumulative
risk
assessment:
Pilot
Cumulative
Analysis
At
the
February
2005
SAP
meeting,
EPA
plans
to
discuss
key
issues
related
to
hazard
assessment,
PBPK/
PD
modeling
of
carbaryl,
drinking
water
exposure
assessment,
and
the
integration
of
hazard
and
exposure.

Hazard
assessment:

EPA
acknowledges
that
there
are
toxicological
characteristics
unique
to
the
N­
methyl
carbamates
which
need
to
be
considered
in
a
cumulative
risk
assessment
for
this
group.
Specifically,
the
mechanism
of
action
for
this
group
of
pesticides
is
carbamylation
of
the
AChE
active
site
leading
to
rapid
recovery
of
inhibition.
OPP
is
collaborating
with
laboratory
scientists
and
statisticians
from
EPA's
National
Health
and
Environmental
Effects
Research
Laboratory
(
NHEERL)
to
evaluate
biological
and
empirical
aspects
of
recovery.
EPA
expects
to
solicit
comment
on
specific
issues
related
to
dose­
response
modeling
of
AChE
data,
empirical
estimation
of
time
to
recovery,
and
the
impact
of
the
laboratory
method
used
to
measure
AChE
inhibition
on
estimates
of
relative
potency.

PBPK/
PD
Modeling
for
Carbaryl:

OPP
is
collaborating
with
scientists
from
EPA's
National
Exposure
Research
Laboratory
(
NERL)
to
develop
a
PBPK/
PD
model
for
carbaryl
within
the
Exposure
Related
Dose
Estimating
Model
(
ERDEM)
Platform
(
Blancato
et
al.,
2002;
Okino
et
al.
2004).
The
carbaryl
model
will
form
the
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basic
structure
of
a
generalized
model
for
the
N­
methyl
carbamates.
A
Quantitative
Structure
Activity
Relationship
(
QSAR)
database
of
physicochemical
descriptors
and
provisional
PK
and
PD
parameter
values
has
been
assembled
for
selected
N­
methyl
carbamates.
The
completeness
and
representativeness
of
the
QSAR
database
will
influence
the
application
of
the
PBPK/
PD
model
for
use
in
the
cumulative
risk
assessment
of
the
N­
methyl
carbamates.
EPA
will
solicit
comment
on
specific
aspects
of
the
appropriate
use
of
ERDEM
for
this
Risk
Assessment.

Drinking
water
exposure
assessment:

Unlike
the
OP
CRA
where
the
only
anticipated
exposure
to
OP
pesticides
in
drinking
water
was
expected
to
be
from
surface
water
sources,
OPP
must
consider
both
surface­
and
ground­
water
sources
of
drinking
water
for
the
N­
methyl
carbamates.
OPP
will
solicit
comment
from
the
SAP
on
the
use
of
one
or
more
existing
ground­
water
models
to
provide
a
pilot
ground­
water
exposure
assessment
for
the
carbamates.
OPP
also
expects
to
request
feedback
from
the
panel
on
approaches
for
refining
regional
drinking
water
exposures
in
the
event
that
such
exposure
from
surface
and/
or
ground­
water
sources
contributes
substantially
to
the
cumulative
exposure
in
one
or
more
regions.

Integration
of
hazard
and
exposure
assessment:

EPA
will
present
a
pilot
cumulative
analysis
of
food,
water,
and
residential
exposure.
This
analysis
will
be
presented
using
three
different
exposure
models:
LifeLine,
CARES,
and
Calendex.
This
presentation
will
also
include
a
discussion
of
the
unique
challenges
related
to
rapid
recovery
of
AChE
inhibition
posed
by
this
group
of
pesticides
and
different
approaches
for
considering
these
characteristics
in
the
quantitative
estimates
of
cumulative
risk.
EPA
expects
to
request
the
panel
to
provide
comment
on
potential
approaches
for
integrating
hazard
and
exposure
for
this
group
and
specifically
characterizing
recovery
in
risk
estimates.
