Page
1
of
3
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
November
30
­
December
1,
2004
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2004­
0320
TUESDAY,
NOVEMBER
30,
2004
Holiday
Inn
Rosslyn
at
Key
Bridge
1900
North
Fort
Myer
Drive
Arlington,
VA
22209
(
703)
807­
2000
DIMETHOATE:
ISSUES
RELATED
TO
HAZARD
AND
DOSE
RESPONSE
ASSESSMENT

8:
30
A.
M.
Introduction
and
Identification
of
Panel
Members
­
Stephen
M.
Roberts,
Ph.
D.
(
FIFRA
SAP
Chair)


8:
40
A.
M.
Administrative
Procedures
by
Designated
Federal
Official
­
Ms.
Myrta
R.
Christian

8:
45
A.
M.
Welcome
­
Mr.
Joseph
J.
Merenda,
Jr.
(
Director,
Office
of
Science
Coordination
and
Policy,
EPA)


8:
50
A.
M.
Opening
Remarks
­
Randolph
Perfetti,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


8:
55
A.
M.
Introduction
and
Background
­
Diana
Locke,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


9:
05
A.
M.
PMRA/
EPA
Collaboration
­
Ms.
Cheryl
Chaffey
(
Pest
Management
Regulatory
Agency,
Canada)


9:
15
A.
M.
Hazard
Characterization:
Pup
Mortality
and
Cholinesterase
Inhibition
Results
­
Kathleen
Raffaele,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


10:
00
A.
M.
BREAK

10:
15
A.
M.
Benchmark
Dose
Analyses
­
Mr.
Philip
Villanueva
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


10:
45
A.
M.
Integration
of
Hazard
and
Dose
Response
Analyses
­
Kathleen
Raffaele,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


12:
00
P.
M.
LUNCH

1:
00
P.
M.
Public
Comments

3:
00
P.
M.
BREAK

3:
15
P.
M.
Public
Comments
(
continued)


5:
00
P.
M.
ADJOURNMENT
Page
2
of
3
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
November
30
­
December
1,
2004
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2004­
0320
WEDNESDAY,
DECEMBER
1,
2004
Holiday
Inn
Rosslyn
at
Key
Bridge
1900
North
Fort
Myer
Drive
Arlington,
VA
22209
(
703)
807­
2000
DIMETHOATE:
ISSUES
RELATED
TO
HAZARD
AND
DOSE
RESPONSE
ASSESSMENT

8:
30
A.
M.
Introduction
and
Identification
of
Panel
Members
­
Stephen
M.
Roberts,
Ph.
D.
(
FIFRA
SAP
Chair)


8:
40
A.
M.
Administrative
Procedures
by
Designated
Federal
Official
­
Ms.
Myrta
R.
Christian

8:
45
A.
M.
Follow­
up
from
Previous
Day's
Discussion
­
Kathleen
Raffaele,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)
­
Ms.
Cheryl
Chaffey
(
Pest
Management
Regulatory
Agency,
Canada)


9:
00
A.
M.
Questions
to
the
Panel
Interpretation
of
the
cholinesterase
activity
and
pup
mortality
results
from
the
dimethoate
developmental
neurotoxicity
(
DNT)
study
and
related
studies.

Question
1.1
Please
comment
on
the
information
available
for
dimethoate
which
characterizes
the
underlying
cause(
s)
of
the
pup
mortality
in
the
dimethoate
DNT
study
and
the
degree
to
which
this
information
can
be
used
to
determine
the
impact
of
maternal
neglect/
maternal
toxicity
on
pup
mortality.
[
Section
II
B
and
Sections
II
C
2,
3,
5b­
d]


10:
00
A.
M.
BREAK

10:
15
A.
M.
Questions
to
the
Panel
(
continued)

Question
1.2
The
results
of
the
cross
fostering
study
suggest
that
the
pup
mortality
observed
at
lower
doses
in
the
main
DNT
study
may
not
be
attributable
to
a
single
dimethoate
exposure.
Please
comment
on
the
evidence
that
supports
or
refutes
this
analysis.
[
Section
II
B
2
and
II
C
5
d]
Page
3
of
3
Question
1.3
After
considering
the
results
of
the
BMD
analyses
for
brain
ChE
inhibition
and
for
pup
mortality,
it
is
proposed
that
brain
ChE
inhibition
be
used
as
the
endpoint
for
the
dimethoate
risk
assessment
for
all
durations
of
exposure
(
e.
g.,
acute,
chronic).
This
would
also
be
protective
for
the
pup
mortality
endpoint,
because
available
data
indicate
that
brain
ChE
inhibition
occurs
at
doses
similar
to
or
lower
than
those
causing
increases
in
pup
mortality.
A
number
of
factors
were
considered
in
developing
this
proposal:


Brain
ChE
inhibition
occurs
at
doses
similar
to
or
lower
than
those
causing
ChE
inhibition
in
other
compartments;


BMD
analyses
results
indicate
a
very
robust
dose­
response
curve
for
brain
ChE
inhibition,
with
similar
BMD
10
values
from
studies
with
varying
modes
of
administration
(
dietary
or
gavage)
and
durations
(
short
term
for
DNT
studies
and
longer
term
for
reproduction
studies);


BMD
analyses
results
indicate
similar
dose­
response
curves
at
all
ages,
with
no
difference
in
BMD
10
values
for
different
age
groups
following
similar
exposure
durations;


Comparison
of
BMR
dose
levels
for
brain
ChE
inhibition
and
pup
mortality
following
repeated
dosing
indicates
that
ChE
inhibition
occurs
at
doses
similar
to
those
associated
with
increases
in
pup
mortality;


Evaluation
of
pup
mortality
data
from
the
cross­
fostering
study
reveals
clear
increases
in
mortality
only
at
the
highest
dose
following
short­
term
exposure,
indicating
that
increased
mortality
at
lower
doses
occurs
only
with
repeated
dosing;


Comparison
of
the
NOAEL
for
increased
pup
mortality
from
limited
dosing
with
the
BMD
10
for
brain
ChE
inhibition
following
a
single
dose
indicates
that
brain
ChE
inhibition
occurs
at
doses
below
those
causing
a
clear
increase
in
pup
mortality.

Please
comment
on
the
evidence
that
supports
or
refutes
this
proposal
(
Sections
IIB
4,
and
II
C).


12:
30
P.
M.
ADJOURNMENT
Please
be
advised
that
agenda
times
are
approximate.
For
further
information,
please
contact
the
Designated
Federal
Official
for
this
meeting,
Ms.
Myrta
Christian,
via
telephone:
(
202)
564­
8450;
fax:
(
202)
564­
8382;
or
email:
christian.
myrta@
epa.
gov
