Page
1
of
5
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
JULY
29­
JULY
30,
2004
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2004­
0173
THURSDAY,
JULY
29,
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
AM
Introduction
and
Identification
of
Panel
Members
­
Stephen
M.
Roberts,
Ph.
D.
(
FIFRA
SAP
Chair)


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

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


8:
50
AM
Opening
Remarks
­
Mr.
Jim
Jones
(
Director,
Office
of
Pesticide
Programs,
EPA)


8:
55
AM
Opening
Remarks
­
Margaret
Stasikowski/
Randolph
Perfetti,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


9:
00
AM
PMRA/
EPA
Joint
Dimethoate
Risk
Assessment
­
Ms.
Cheryl
Chaffey
(
Pest
Management
Regulatory
Agency,
Canada)


9:
10
AM
Purpose:
Dimethoate
Issues
Related
to
Hazard
and
Dose
Response
Assessment
­
Kathleen
Raffaele,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


9:
20
AM
Developmental
Neurotoxicity
Study
Related
Issues
­
Kathleen
Raffaele,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


9:
45
AM
BREAK

10:
00
AM
Developmental
Neurotoxicity
Study
Related
Issues
(
continued)


11:
00
AM
Dermal
Penetration
Factor
­
Byong­
Han
(
Paul)
Chin,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA)


11:
40
AM
Summary
and
Questions
to
the
Panel
­
Kathleen
Raffaele,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA),
Byong­
Han
(
Paul)
Chin,
Ph.
D.
(
Health
Effects
Division,
Office
of
Pesticide
Programs,
EPA),
and
Ms.
Cheryl
Chaffey
(
Pest
Management
Regulatory
Agency,
Canada)


12:
00
PM
LUNCH

1:
00
PM
Public
Comments

2:
30
PM
BREAK

2:
45
PM
Public
Comments
(
continued)
Page
2
of
5

5:
00
PM
ADJOURNMENT
Page
3
of
5
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
JULY
29­
JULY
30,
2004
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2004­
0173
FRIDAY,
JULY
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
AM
Introduction
and
Identification
of
Panel
Members
­
Stephen
M.
Roberts,
Ph.
D.
(
FIFRA
SAP
Chair)


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

8:
45
AM
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
AM
Questions
to
the
Panel
Issue
1.
Interpretation
of
the
results
from
the
developmental
neurotoxicity
(
DNT)
and
related
comparative
ChE
inhibition
and
cross­
fostering
studies
Question
1.1
In
2001,
EPA
was
notified
of
unanticipated
adverse
effects
in
the
DNT
study.
The
adverse
effects
observed
were
a
potential
increase
in
the
number
of
deaths
in
young
pups
when
dams
were
exposed
orally
to
dimethoate
during
gestation
and
lactation.
Following
a
detailed
review
of
this
study,
both
EPA
and
PMRA
have
determined
that
there
is
a
doserelated
increase
in
pup
mortality.
Typically
in
developmental
and
reproductive
toxicity
studies,
the
litter
is
considered
the
appropriate
unit
of
analysis.
As
part
of
the
review
of
the
dimethoate
DNT
study,
the
individual
pup
has
been
treated
both
qualitatively
and
statistically
as
the
appropriate
unit
of
analysis.
This
evaluation
has
included
pups
which
died
and
whole
litters
which
were
humanely
sacrificed
and
includes,
for
example,
mortality
of
15
pups
which
was
limited
to
a
litter
from
a
single
dam
at
0.5
mg/
kg/
day.

Please
comment
on
the
biological
and
statistical
considerations
important
in
evaluating
the
dose­
response
data
such
as
the
pup
mortality
incidence
reported
in
the
DNT.
Page
4
of
5
Question
1.2
Section
II.
D
of
the
issue
paper
describes
the
total
weight
of
the
evidence
used
by
EPA
and
PMRA
to
reach
their
conclusions
regarding
the
pup
mortality
observed
in
the
main
DNT
study.

Please
comment
on
the
clarity
and
completeness
of
this
discussion.

Question
1.3
The
underlying
cause
of
the
pup
mortality
is
unclear.
The
study
design
for
the
DNT
study
includes
both
pre­
and
post­
natal
exposures;
the
impact
of
in
utero
exposure
on
pup
mortality
cannot
be
distinguished
from
post­
natal
exposures
(
either
through
lactation
or
direct
dosing)
in
this
study.
In
order
to
further
characterize
the
cause
of
pup
mortality,
and
specifically,
the
influence
of
maternal
neglect,
the
pesticide
registrant
designed
and
performed
a
cross­
fostering
study
where
untreated
dams
reared
pups
exposed
in
utero;
treated
dams
reared
pups
not
exposed
in
utero;
and
treated
dams
reared
their
own
litters.
EPA
and
PMRA
have
reviewed
the
pup
mortality
reported
in
the
cross­
fostering
study
along
with
observations
specifically
targeted
to
evaluate
maternal
neglect
(
e.
g.,
maternal
restlessness,
scattering
of
pups,
absence
of
milk
in
the
stomach).
These
data
have
been
evaluated
in
context
with
observations
from
the
main
DNT
study
and
related
comparative
ChE
and
range­
finding
studies.

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
impact
of
maternal
neglect
on
pup
mortality.


10:
30
AM
BREAK

10:
45
AM
Questions
to
the
Panel
(
continued)

Issue
2.
Determination
of
a
dermal
penetration
factor
for
dimethoate
Question
2.1
Three
different
studies
evaluating
dermal
penetration
are
available.
These
include:
an
in
vitro
study
with
rat
and
human
tissue;
an
in
vivo
study
conducted
with
dimethoate
prepared
in
aqueous
carboxymethyl
cellulose
suspension;
and
an
in
vivo
study
conducted
with
dimethoate
prepared
in
commercial
formulations.
Although
each
study
has
scientific
merit,
there
are
uncertainties
associated
with
each
study:
namely,
effects
of
different
vehicle/
solvent
used
in
the
in
vivo
studies
and
lack
of
accuracy
of
estimating
in
vivo
dermal
absorption
by
in
vitro
procedure
in
the
rat.

Please
comment
on
the
utility
of
these
studies
for
purposes
of
estimating
a
dermal
absorption
factor
for
dimethoate.
Page
5
of
5

12:
15
PM
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
