Document ID: EPA-HQ-OPPT-2002-0059-0017
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-05-07T04:00Z

MEMORANDUM
SUBJECT:
Transmittal
of
the
Meeting
Minutes
of
the
Endocrine
Disruptor
Methods
Validation
Subcommittee
under
the
National
Advisory
Council
for
Environmental
Policy
and
Technology
(
NACEPT),
held
December
4,
2002.

TO:
Dorothy
Bowers,
Chair
National
Advisory
Council
for
Environmental
Policy
and
Technology
Office
of
Cooperation
and
Environmental
Management
And
Gwen
Whitt,
Designated
Federal
Official
National
Advisory
Council
for
Environmental
Policy
and
Technology
Office
of
Cooperation
and
Environmental
Management
FROM:
Jane
Scott
Smith,
Designated
Federal
Official
/
s/
NACEPT
Endocrine
Disruptor
Methods
Validation
Subcommittee
Office
of
Science
Coordination
and
Policy/
OPPTS
THRU:
Joseph
Merenda,
Director
/
s/
Chair
of
Endocrine
Disruptor
Methods
Validation
Subcommittee
Office
of
Science
Coordination
and
Policy/
OPPTS
Please
find
attached
the
minutes
of
the
NACEPT
Endocrine
Disruptor
Methods
Validation
Subcommittee
sixth
open
meeting
that
was
conducted
as
the
second
teleconference
and
held
in
Washington,
D.
C.
December
4,
2002.
The
focus
of
this
meeting
was
a
Detailed
Review
Paper
(
DRP),
on
the
Fish
Lifecycle
Assay.

Information
about
NACEPT
EDMVS
meetings
and
activities
can
be
obtained
from
the
website
at
http://
www.
epa.
gov/
scipoly/
oscpendo,
the
OPPT
Docket,
[
OPPT
2002­
0059]
at
(
202)
566­
0280,
or
by
going
to
www.
epa.
gov/
epahome/
dockets.
htm
and
searching
for
OPPT­
2002­
0059.
Interested
persons
are
invited
to
contact
Jane
Smith,
EDMVS
Designated
Federal
Official
(
DFO),
via
e­
mail
at
smith.
jane­
scott@
epa.
gov.
cc:

Sonia
Altieri
Charles
Auer
Daiva
Balkus
Dennis
Deziel
Susan
Hazen
Stephen
Johnson
James
Jones
William
Jordan
Marcia
Mulkey
Margaret
Schneider
Adam
Sharp
OPPT
Docket
2002­
0059
MEETING
MINUTES
OF
ENDOCRINE
DISRUPTOR
METHODS
VALIDATION
SUBCOMMITTEE
A
Subcommittee
of
The
National
Advisory
Council
for
Environmental
Policy
and
Technology
TELECONFERENCE
ON
DECEMBER
4,
2002
AT
RESOLVE,
1255
23RD
STREET,
N.
W.
SUITE
275
WASHINGTON,
D.
C.

The
Topic
of
this
meeting
was
Presentation
and
Discussion
of
the
Fish
Lifecycle
Detailed
Review
Paper
(
DRP).

____________/
s/__
________________
/
s/________________________

Jane
Scott
Smith,
DFO
Joseph
Merenda,
Chair
Endocrine
Disruptor
Methods
Validation
Endocrine
Disruptor
Methods
Validation
Subcommittee
under
the
National
Subcommittee
under
the
National
Advisory
Council
for
Environmental
Advisory
Council
for
Environmental
Policy
and
Technology
Policy
and
Technology
Date:
______
2/
6/
2003_______
Date:
2/
13/
2003______
_
____

i
TABLE
OF
CONTENTS
Page
Official
Signatures......................................................................
i
Attendees...................................................................................
2
Presenters
.................................................................................
3
Public
Commenters
....................................................................
3
Notice.........................................................................................
4
Meeting
Agenda..........................................................................
5
Meeting
Introduction
and
Summary............................................
7
Attachment
A
                     
15
2
EDMVS
Members
in
Attendance
at
the
December
2002
Teleconference
Attended
in
Person
at
RESOLVE
Joseph
Merenda,
Chair
William
Benson,
Ph.
D.,
Co­
Chair
U.
S.
EPA
U.
S.
EPA
William
Stokes,
D.
V.
M.
NIEHS
Attended
Via
Telephone
Theodora
Colborn,
Ph.
D
Ron
Miller,
Ph.
D
World
Wildlife
Fund
The
Dow
Chemical
Company
Robert
Combs
,
Ph.
D.
Susan
C.
Nagel,
Ph.
D.
Fund
for
Replacement
of
Animals
University
of
Missouri­
Columbia
In
Medical
Experiments
James
W.
"
Willie"
Owens,
Ph.
D.
Rodger
D.
Curren,
Ph.
D.
The
Procter
&
Gamble
Company
Institute
for
In
Vitro
Sciences,
Inc
(
on
temporary
detail
to
OECD)

J.
Charles
Eldridge,
Ph.
D.
Thomas
L.
Potter,
Ph.
D.
Wake
Forest
University
USDA­
Agriculture
Research
Service
Robert
J.
Kavlock,
Ph.
D.
Theodore
H.
Schettler
M.
D.,
MPH
U.
S.
EPA
Science
&
Environ.
Health
Network
William
Kelce,
Ph.
D.
Shane
A.
Snyder,
Ph.
D.
Pharmacia
Corporation
Southern
NV
Water
Authorilty
Nancy
K.
Kim,
Ph.
D.
James
T.
Stevens.
Ph.
D.
NY
State
Department
of
Health
Wake
Forest
University
Timothy
Kubiak,
M.
P.
H.
Glen
Van
Der
Kraak,
Ph.
D.
U.
S.
Fish
and
Wildlife
Service
University
of
Guelph
Gerald
A.
LeBlanc,
Ph.
D.
James
D.
Yager,
Jr.,
Ph.
D.
North
Carolina
State
University
Johns
Hopkins
University
Facilitator
Designated
Federal
Official
Paul
De
Morgan
Jane
Scott
Smith
RESOLVE
Office
of
Science
Policy
and
Coordination
3
Presenter
Presenter
Les
Touart
EPA,
OSCP
Public
Oral
Commenters
Public
Commenters
Rick
Becker
ACC
Troy
Seidle
PETA
4
NOTICE
This
meeting
summary
has
been
written
as
part
of
the
activities
of
the
National
Advisory
Council
on
Environmental
Policy
and
Technology
(
NACEPT),
Endocrine
Disruptor
Methods
Validation
Subcommittee
(
EDMVS).
This
meeting
summary
has
not
been
reviewed
for
approval
by
the
United
States
Environmental
Protection
Agency
(
Agency)
and,
hence,
the
contents
of
the
meeting
summary
do
not
necessarily
represent
the
views
and
policies
of
the
Agency,
nor
of
other
agencies
in
the
Executive
Branch
of
the
Federal
government,
nor
does
mention
of
trade
names
or
commercial
products
constitute
a
recommendation
for
use.

The
NACEPT
EDMVS
was
established
in
partial
fulfillment
of
a
Congressional
statute.
When
Congress
amended
the
Federal
Food
Drug
and
Cosmetics
Act
(
FFDCA)
in
the
Food
Quality
Protection
Act
(
FQPA)
of
1996,
it
directed
the
U.
S.
Environmental
Protection
Agency
(
EPA)
to
develop
a
screening
program
to
determine
whether
certain
substances
may
have
hormonal
effects
in
humans.
To
ensure
that
EPA
has
the
best
and
most
up­
to­
date
advice
available
regarding
the
validation
of
the
screens
and
tests
in
the
EDSP,
EPA
established
the
Endocrine
Disruptor
Methods
Validation
Subcommittee
(
EDMVS)
under
the
NACEPT.
The
EDMVS
provides
independent
advice
and
counsel
to
the
Agency
through
NACEPT
on
scientific
and
technical
issues
related
to
validation
of
the
EDSP
Tier
I
and
Tier
II
assays,
including
advice
on
methods
for
reducing
animal
use,
refining
procedures
involving
animals
to
make
them
less
stressful,
and
replacing
animals
where
scientifically
appropriate.
The
EDMVS
held
their
first
meeting
in
October
of
2001,
their
second
meeting
in
December
2001,
and
their
third
meeting
in
March
2002.
The
fourth
meeting
of
the
EDMVS
was
conducted
as
an
international
teleconference
in
June
2002.
The
fifth
meeting
was
in
July
of
2002
and
sixth
was
conducted
as
an
international
teleconference
in
December
of
2002.

The
December
4,
2002
open
meeting
(
teleconference)
of
the
EDMVS
was
announced
in
the
Federal
Register
on
November
14,
2002
(
Volume
67,
Number
220).
Further
information
about
NACEPT
EDMVS
meetings
and
activities
can
be
obtained
from
its
website
at
http://
www.
epa.
gov/
scipoly/
oscpendo
or
the
OPPT
Docket
at
(
202)
566­
0280.
INTERESTED
PERSONS
ARE
INVITED
TO
CONTACT
Jane
Smith,
EDMVS
Designated
Federal
Official
(
DFO),
via
e­
mail
at
smith.
jane­
scott@
epa.
gov.
5
National
Advisory
Council
for
Environmental
Policy
and
Technology
(
NACEPT)

Endocrine
Disruptor
Methods
Validation
Subcommittee
(
EDMVS)

Meeting
by
Conference
Call
December
4,
2002
10:
00
a.
m.
 
12:
00
noon
EST
Proposed
Agenda
Members
of
the
public
may
join
this
conference
call
in
person
at
the
conference
room
in
the
RESOLVE
offices
at
1255
23rd
St.
NW,
Suite
275,
Washington,
DC.
To
register
to
participate
by
phone,
please
contact
Jane
Smith,
designated
federal
official
for
the
EDMVS,
at
smith.
janescott
epa.
gov
or
(
202)
564­
8476.
Also
note
that
members
of
the
public
who
would
like
to
make
comments
during
the
conference
call
need
to
contact
Ms.
Smith
prior
to
the
meeting.

Meeting
Objective:
 
Provide
comments
and
advice
on
the
Fish
Lifecycle
DRP
(
Tier
II).

10:
00
 
10:
05
Phoning
in
10:
05
­
10:
10
Welcome
and
Opening
Comments
o
Roll
Call
o
Overview
of
FACA
Requirements
10:
10
 
10:
30
Fish
Lifecycle
DRP
(
Tier
II)
Presentation
Dr.
Les
Touart,
Office
of
Science
Coordination
and
Policy
(
OSCP),
EPA
10:
30
 
11:
40
Discussion
on
Fish
Lifecycle
DRP
The
purpose
of
this
DRP
is
to
define
the
basis
and
purpose
of
the
proposed
two
generation
test
for
evaluating
endocrine
effects.
The
DRP
summarizes,
explains,
and
documents
decisions
regarding
the
relevant
principles,
methods,
and
techniques
recommended
for
an
initial
protocol
with
four
candidate
species
of
fish
(
fathead
minnow,
zebrafish,
medaka,
and
sheepshead
minnow),
and
identifies
issues
that
might
require
prevalidation
studies
to
adequately
address
information
gaps.
Please
use
the
following
questions
as
a
guide
for
your
feedback
to
EDSP:

1.
Does
the
EDMVS
agree
that
the
two­
generation
method
recommended
and
applicable
to
four
species
of
fish
is
appropriate?

2.
Does
the
EDMVS
agree
that
prevalidation
should
evaluate
the
increased
sensitivity
of
a
two­
generation
design
over
the
existing
fish
full
life­
cycle
standard
practice?

3.
Does
the
EDMVS
agree
that
prevalidation
should
demonstrate
the
sensitivity
and
reproducibility
for
each
species
in
the
recommended
protocol?
6
4.
Does
the
EDMVS
have
suggestions
to
improve
the
DRP?

11:
40
 
11:
55
Public
Comment
Members
of
the
public
who
would
like
to
make
comments
during
the
conference
call
must
contact
Jane
Smith,
designated
federal
official
for
the
EDMVS,
at
smith.
jane­
scott@
epa.
gov
or
(
202)
564­
8476.
Members
of
the
public
are
requested
to
focus
their
comments
on
issues
related
to
the
Fish
Lifecycle
DRP
to
the
extent
possible.

11:
55
 
12:
00
Next
Steps
12:
00
Adjourn
7
Introduction
The
Office
of
Science
Coordination
and
Policy's
Endocrine
Disruptor
Screening
program
established
the
Endocrine
Disruptor
Methods
Validation
Subcommittee
(
EDMVA)
under
The
National
Advisory
Council
for
Environmental
Policy
and
Technology
(
NACEPT).
All
of
the
subcommittee
meetings
are
held
in
accordance
with
the
Federal
Advisory
Committee
Act
and
are
always
open
to
the
public
with
time
available
for
public
comment.
The
first
EDMVS
meeting
was
held
in
October
2001.
That
initial
meeting
brought
the
members
together
to
review
the
mission
statement,
the
operating
procedures
and
discuss
subcommittee
roles
and
responsibilities.
The
second
meeting,
held
in
December
2001,
was
the
first
time
the
subcommittee
members
were
presented
with
specific
questions
regarding
assay
protocols.
The
third
meeting,
held
March
2002,
continued
discussions
on
protocols
as
well
as
some
discussions
on
the
validation
process,
Core
Chemicals,
`
low
dose'
and
means
of
assessing
human
health
effects.
The
fourth
meeting,
held
as
a
teleconference,
was
wholly
concerned
with
the
Steroidogenesis
assay.
The
fifth
meeting
continued
discussions
on
protocols
as
well
as
some
discussions
on
the
EDMVS
work
plan,
the
criteria
for
screens
and
general
dose
setting
issues.

Endocrine
Disruptor
Methods
Validation
Subcommittee
(
EDMVS)
Meeting
by
Conference
Call
December
4,
2002
Meeting
Summary
­
Final
­

On
December
4,
2002,
the
U.
S.
Environmental
Protection
Agency
(
EPA)
convened
a
meeting
of
the
Endocrine
Disruptor
Methods
Validation
Subcommittee
(
EDMVS)
by
conference
call.
The
objective
of
the
meeting
was
to
provide
comments
and
advice
on
the
Draft
Detailed
Review
Paper
on
a
Fish
Two­
Generation
Toxicity
Test.
The
meeting
took
place
in
Washington,
DC;
however,
many
of
the
EDMVS
members,
as
well
as
some
members
of
the
public,
participated
by
phone.

Copies
of
presentation
slides
and
other
materials
distributed
at
the
meeting
may
be
obtained
by
contacting
Jane
Smith,
the
designated
federal
official
for
EDMVS,
at
smith.
jane­
scott@
epa.
gov
or
202/
564­
8476.
The
materials
also
are
available
on
the
EPA
website
at
http://
www.
epa.
gov/
scipoly/
oscpendo/
edmvs.
htm.
EPA
has
established
an
administrative
record
for
this
meeting
under
docket
control
number
OPPT­
2002­
0059.
The
docket
is
available
for
public
viewing
at
the
EPA
Docket
Center,
Rm.
B102
 
Reading
Room,
EPA
West,
1301
Constitution
Ave.,
NW.,
Washington,
DC.
The
center
is
open
from
8:
30
a.
m.
to
4:
30
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
8
The
center's
phone
number
is
(
202)
566­
1744
and
the
telephone
number
for
the
OPPT
Docket,
which
is
located
in
the
EPA
Docket
Center,
is
(
202)
566­
0280.

I.
Opening
Comments,
Roll
Call,
and
Agenda
Review
Paul
De
Morgan,
senior
mediator
with
RESOLVE,
welcomed
EDMVS
members
and
other
participants
to
the
meeting
and
thanked
them
for
attending
by
phone
or
in
person.
He
introduced
Joe
Merenda,
Director
of
the
Office
of
Science
Coordination
and
Policy
(
OSCP)
and
new
chair
of
the
EDMVS.
Mr.
Merenda
highlighted
the
Endocrine
Disruptor
Screening
Program
(
EDSP)
as
one
of
the
most
visible
and
critical
of
that
office's
functions,
and
he
expressed
his
enthusiasm
for
being
involved
with
the
subcommittee
and
learning
more
about
the
issues.

Jane
Smith,
designated
federal
official
for
the
EDMVS,
explained
that
the
meeting
was
being
held
in
accordance
with
the
Federal
Advisory
Committees
Act
(
FACA)
and
all
materials
distributed
would
be
available
through
the
docket
and
on
the
website.
She
invited
anyone
experiencing
problems
with
the
website
or
other
concerns
to
contact
her.
She
asked
participants
to
send
her
the
comments.
All
written
comments
will
be
posted
on
the
EDSP
website
at
the
address
noted
above.

Mr.
De
Morgan
did
a
roll
call
of
EDMVS
members
and
public
participants
who
had
registered
and
asked
other
participants
to
announce
their
names.
(
Please
see
attachment
A
for
a
list
non­
member
meeting
attendees.)
He
asked
subcommittee
members
to
let
him
know
at
the
end
of
the
conference
call
if
the
two­
hour
time
period
for
the
discussion
was
insufficient
to
address
all
topics.
He
encouraged
participants
to
submit
written
comments
to
Ms.
Smith
if
they
were
unable
to
raise
them
on
the
call.
He
then
reviewed
the
meeting
agenda.

II.
Fish
Two­
Generation
Toxicity
Test
DRP
Les
Touart,
OSCP,
gave
a
slide
presentation
on
A
Fish
Two­
Generation
Toxicity
Test
Detailed
Review
Paper
(
DRP).
He
noted
the
methods
used
in
the
DRP
analysis,
including
an
online
literature
search,
interviews
with
experts,
and
an
external/
internal
peer
review.
He
explained
existing
fish
lifecycle
tests
do
not
address
relevant
biochemical,
morphological,
and
behavioral
endpoints.
Further,
transgenerational
endocrine
effects
are
not
assessed
in
current
tests.
For
these
reasons,
EPA
recommends
replacing
existing
lifecycle
tests
with
a
two­
generation
test
that
addresses
these
factors.
Dr.
Touart
covered
characteristics
and
strengths
and
weaknesses
of
the
fathead
minnow
(
Pimephales
promelas),
medaka
(
Oryzias
latipes),
zebrafish
(
Danio
rerio),
and
the
sheepshead
minnow
(
Cyprinodon
variegates)
test
species.
Other
presentation
comments
included
the
following:

For
candidate
replacement
tests,
the
principal
route
of
administration
of
chemical
9
exposure
is
aqueous,
other
optional
routes
include
dietary,
intravascular,
and
intraperitoneal
injection.

Measurement
endpoints
include
morphological
alterations,
reproductive
performance,
and
biochemical
measures
including
vitellogenin
induction.

Vitellogenin
is
measured
using
direct
and
indirect
quantification
of
vitellogenin
protein,
quantification
of
vitellogenin
mRNA,
and
mass
spectrometry.

Candidate
protocols
include
partial
life­
cycle,
full
life­
cycle,
multigeneration,
and
two­
generation
tests,
and
the
DRP
recommends
moving
forward
with
the
proposed
two­
generation
protocol.

This
test
exposes
the
adult
P,
full
F1
generation,
and
measures
F2
viability,
measuring
biological
endpoints
for
the
adults
and
both
subsequent
generations.

Dr.
Touart
noted
the
significant
data
gaps
that
exist
but
commented
that
information
is
improving
quickly.
He
also
outlined
implementation
considerations,
including
prevalidation
studies
and
validation
of
the
study
design
through
interlaboratory
comparisons.

Following
his
presentation,
Dr.
Touart
answered
questions
of
clarification
from
EDMVS
members.
He
explained
that
the
concept
of
the
partial
lifecycle
test
is
similar
to
the
short
term
reproduction
test
that
uses
breeding
groups
and
exposure
information
to
guide
the
selection
of
spawning
groups
for
exposure
and
helps
to
reduce
variability.

The
purpose
of
the
protocol,
as
a
tier
2
test,
is
defined
as
definitively
evaluating
endocrine
potential
and
adverse
effects
of
a
compound
on
the
lifecycle,
including
survival,
ability
to
reproduce,
and
growth.
Further,
transgenerational
factors
such
as
the
viability
of
offspring
are
intended
to
be
tested.
This
protocol
will
address
endpoints
relevant
for
predicting
population
effects,
which
are
an
important
component
for
ecological
risk
assessments.
The
protocol
would
be
triggered
for
a
compound
when
the
tier
1
screen
or
other
available
information
indicate
a
potential
for
interfering
with
hormone
activity.

A
member
asked
whether
there
are
differences
between
EPA's
approach
and
that
of
OECD,
in
that
OECD
has
a
3­
tier
approach
with
a
step
between
mechanistic
screens
and
two­
generation
tests.
Dr.
Touart
explained
there
is
not
discordance,
as
OECD
has
not
established
an
official
tiered
framework.
While
endpoints
used
at
the
screening
level
are
still
under
discussion,
any
indication
that
a
compound
will
impact
the
endocrine
system
of
a
fish
species
will
trigger
a
further
evaluation
of
that
compound.
He
agreed
that
additional
information
may
sometimes
be
needed
before
beginning
a
twogeneration
test,
and
an
intermediate
tier
could
help
with
range­
finding.
However,
a
compound
found
to
act
on
the
endocrine
system
will
require
a
definitive
test
such
as
the
two­
generation
test,
regardless
of
whether
a
partial
lifecycle
test
or
other
intermediate
level
test
is
run
first.
The
member
disagreed
that
a
two­
generation
test
would
be
necessary
in
all
cases.
10
III.
EDMVS
Member
Discussion
of
the
Fish
Lifecycle
DRP
Mr.
De
Morgan
referred
members
to
the
discussion
questions
listed
in
the
agenda
and
asked
for
their
input,
noting
that
the
first
was
a
two­
part
question
(
as
shown
below).
Because
of
interrelated
nature
of
the
questions,
EDMVS
members
touched
on
all
four
questions
throughout
the
course
of
the
conference
call.
Thus,
the
comments
summarized
under
each
of
the
questions
below
may
overlap
across
questions.

1a.
Does
the
EDMVS
agree
that
the
two­
generation
method
recommended
in
the
DRP
is
appropriate
and
an
improvement
over
the
previous
fathead
minnow
tests?

A
member
emphasized
the
importance
of
assessing
egg
or
embryo
exposure
to
the
chemical
and
expressed
a
concern
that
14­
21
days
of
exposure
would
not
be
sufficient
to
establish
steady
state
for
more
lipophilic
chemicals,
and
therefore
would
not
expose
the
egg
or
embryo.
He
noted
that
the
multigeneration
test
would
better
handle
egg/
embryo
exposure.
Alternatively,
the
two­
generation
test
could
forego
the
F2
generation
and
instead
lengthen
parental
exposure
and
then
take
the
F1
generation
to
full
reproductive
maturity.
Another
member
noted
that
the
multigeneration
test
has
the
advantage
of
exposing
all
lifecycle
stages.

A
member
suggested
comparing
the
two­
generation
test
with
existing
protocols
to
better
understand
the
unique
benefits
of
the
proposed
test.
Dr.
Touart
responded
that
EPA
is
already
considering
doing
an
evaluation
of
the
two­
generation
and
full
lifecycle
test.
He
also
said
they
could
consider
conducting
additional
comparisons.

One
member
commented
that
since
fish
are
not
covered
by
the
Animal
Welfare
Act,
these
validation
studies
should
be
conducted
in
accordance
with
the
Public
Health
Service
Policy
on
the
Humane
Care
and
Use
of
Laboratory
Animals,
which
is
applicable
to
all
vertebrate
species.
He
added
that
this
would
ensure
that
all
animal
care
and
use
was
reviewed
and
overseen
by
an
animal
care
and
use
committee,
and
that
such
care
and
use
was
accomplished
in
accordance
with
the
National
Research
Council
Guide
for
the
Care
and
Use
of
Laboratory
Animals.

1b.
Are
the
four
species
(
fathead
minnow,
medaka,
zebrafish,
and
sheepshead
minnow)
appropriate
candidates
for
this
test?

A
member
asked
why
it
is
necessary
to
use
four
species
of
fish,
and,
if
all
four
were
used,
how
data
would
be
interpreted.
Another
member
pointed
out
that
there
are
international
species
preferences,
and
the
prevalidation
stage
is
the
time
to
determine
how
the
different
species
compare.
Dr.
Touart
explained
that
the
medaka
and
zebrafish
were
included
as
candidates
because
of
their
favor
in
other
countries.
The
sheepshead
minnow
was
added
for
practicality,
as
this
species
has
a
historical
context
and
brings
in
the
ecological
context
of
estuarine/
marine
effects.
Dr.
Touart
highlighted
the
importance
of
maintaining
cross­
species
comparisons
and
extrapolations.
These
species
are
advantageous
both
in
EPA's
familiarity
with
them
as
well
as
their
potential
to
be
11
accepted
and
compared
internationally.
He
noted
that
existing
methodologies
are
somewhat
limited
in
their
international
applicability.
A
member
added
that
testing
the
protocol
with
all
four
species
early
on
will
result
in
more
information
and,
hopefully,
fewer
animals
would
be
needed
once
the
test
is
validated
and
part
of
the
battery.

A
member
suggested
conducting
a
retrospective
review
of
existing
data
to
determine
what
is
known
about
comparative
sensitivity
between
species.
A
pilot
study
could
also
help
determine
differences
in
sensitivity
for
effects
at
low
concentrations
for
weak
acting
chemicals
and
could
save
many
animals
in
later
testing.
A
member
agreed
that
governments
should
be
able
to
detect
whether
there
are
species­
specific
effects,
and
another
EDMVS
member
highlighted
the
importance
of
ensuring
that
data
collected
will
have
mutual
acceptance
in
the
international
community.

One
member
said
that
EPA
should
consider
using
species
for
tier
2
tests
for
which
data
has
been
collected
in
tier
1
screens,
especially
if
the
sensitivity
of
all
four
species
is
comparable.
Gary
Ankley,
EPA,
said
that
there
is
no
reason
to
suspect
the
species
would
differ
greatly
with
respect
to
sensitivity,
especially
when
tested
in
conserved
systems.
Differences
in
sensitivity
would
likely
be
related
to
experimental
design
rather
than
innate
differences
in
the
species.
Dr.
Ankley
shared
that
the
decision
depends
mostly
on
practicality
and
geopolitical
preferences
for
particular
species.

2.
Does
the
EDMVS
agree
that
prevalidation
should
evaluate
the
increased
sensitivity
of
a
two­
generation
design
over
the
existing
fish
full
lifecycle
standard
practice?

A
member
suggested
that
the
partial
lifecycle
test
be
considered
along
with
the
twogeneration
design.
Another
member
commented
that
the
partial
lifecycle
test
does
not
have
full
exposure
for
maternal
uptake
and
exposure
to
offspring.
Dr.
Touart
referenced
the
previous
suggestion
to
investigate
the
multigeneration
test
as
well.
Another
member
agreed
that
the
multigeneration
test
should
be
evaluated
along
with
the
two­
generation
test,
as
it
reflects
co­
exposure
to
other
types
of
information
such
as
salinity
levels
in
the
aqueous
environment.

A
member
supported
using
the
historical
database
for
the
partial
and
full
lifecycle
test,
noting
that
there
is
prevalidation
information
available
for
full
lifecycle
tests
in
the
fathead
and
sheepshead
minnows.
Rather
than
proposing
new
compounds,
he
asked
EDMVS
members
to
share
their
thoughts
about
using
the
existing
database
of
compounds
to
conduct
multigeneration
or
two­
generation
tests.
One
member
encouraged
this
plan,
adding
that
results
should
be
compared
to
those
of
early
life
stage
test
results
to
determine
the
added
value
of
the
two­
generation
test.
Another
member
raised
the
issue
that
previous
evaluations,
such
as
early
life
stage
studies,
did
not
include
endocrine
endpoints.

Members
asked
about
the
contents
of
the
database,
conclusions
that
can
be
drawn
from
it,
and
the
general
practicality
of
using
these
data.
Dr.
Touart
explained
that
the
data
reviews
are
secondary
information
within
EPA's
files,
but
the
actual
studies
would
have
to
be
released
from
the
companies
involved.
He
added
that
there
have
been
12
previous
reviews
of
EPA's
fish
lifecycle
data
set
in
combination
with
other
data
sets,
and
those
discussions
and
conclusions
could
be
made
available
to
the
subcommittee.
Dr.
Touart
also
called
the
subcommittee's
attention
to
EPA's
draft
proposal
to
OECD
on
the
fish
two­
generation
guideline,
which
highlights
EPA's
plan
to
make
ample
use
of
international
resources
and
depend
as
much
as
is
feasible
on
retrospective
analyses.

3.
Does
the
EDMVS
agree
that
prevalidation
should
demonstrate
the
sensitivity
and
reproducibility
for
each
species
in
the
recommended
protocol?

The
group
began
by
discussing
routes
of
exposure.
Members
commenting
on
route
of
exposure
indicated
support
for
aqueous
exposure
as
the
most
relevant
and
practical
route,
especially
considering
that
the
preponderance
of
data
available
is
based
on
this
route
of
exposure.
Regarding
other
routes
considered
by
EPA
(
dietary
and
direct
injection
techniques),
Dr.
Touart
indicated
that
these
exposures
would
be
used
only
in
a
special
case.
He
agreed
that,
in
general,
aqueous
exposure
would
be
the
most
ecologically
relevant
route.

A
member
asked
whether
the
fate
of
chemicals
would
be
tested
to
determine
whether
they
are
detectable
in
water
or
food.
Dr.
Touart
responded
that
if
a
compound
has
no
strong
exposure
potential,
it
is
unlikely
that
it
would
move
into
tier
2.
He
reiterated
that
EPA
would
focus
on
the
aqueous
route
of
administration
in
prevalidation
because
the
majority
of
compounds
would
act
through
that
route.
A
member
suggested
that
using
dietary
exposure
would
require
a
validation
or
prevalidation
study
separate
from
tests
using
aqueous
administration.

Some
members
revisited
the
issue
of
steady
state,
pointing
out
that
for
chemicals
with
special
characteristics,
such
as
lipophilic
compounds,
the
route
and
length
of
exposure
requires
unique
consideration.
One
member
suggested
that
EPA
consult
the
literature
on
this
matter.

Mr.
De
Morgan
summarized
members'
suggestions,
noting
that
EPA
should
be
explicit
about
steady
state
and
its
relevance
to
routes
of
exposure
when
completing
protocols.
A
member
added
that
EPA
should
be
aware
of
any
variability
related
to
whether
test
subjects
reach
steady
state
and
thus
the
comparability
of
endpoints.

4.
Does
the
EDMVS
have
suggestions
to
improve
the
DRP?

Members
asked
EPA
to
include
comparisons
with
database
information
relevant
to
the
protocol
in
the
DRP,
as
these
comparisons
would
be
helpful
in
getting
a
sense
of
the
variability
in
endpoints.
One
member
noted
that
some
existing
data
are
reflected
in
the
DRP,
and
these
references
should
be
included.
Dr.
Touart
explained
that
some
data
were
from
EPA
studies
and
can
be
shared.
EPA
can
also
share
their
reviews
of
data
from
secondary
research,
but
the
actual
studies
would
have
to
be
released
by
registrants.
Before
proceeding,
EPA
would
need
to
determine
the
relevance
of
existing
data
to
this
test.
13
A
member
suggested
that
bringing
closure
to
the
discussion
of
different
protocols
would
improve
the
DRP.
He
added
that
some
of
the
vitellogenin
techniques
seem
time
consuming
and
asked
whether
a
more
rapid
method
was
available
for
tests.
Dr.
Touart
agreed
that
the
DRP
could
do
a
more
thorough
job
of
drawing
conclusions.
Regarding
vitellogenin,
Dr.
Touart
explained
that
there
is
ongoing
research
to
compare
methods.

In
response
to
a
question
on
steroid
receptors,
Dr.
Touart
encouraged
members
to
send
comments.
These
and
any
other
comments
from
the
EDMVS
or
the
public
would
be
most
helpful
if
received
by
the
first
week
of
January.

IV.
Public
Comment
Rick
Becker,
American
Chemistry
Council
Dr.
Becker
commented
that
geopolitical
realities
need
to
be
addressed,
and
EPA
should
take
a
leadership
role
with
OECD
in
discussing
comparability.
He
stressed
that
mutual
acceptance
of
data
is
critical,
and
EPA
should
plan
for
it
up
front.
A
comparison
of
the
protocols
is
needed
and
must
determine
the
value
added
of
the
longer,
more
expensive
studies.
Dr.
Becker
asked
EPA
to
consider
both
type
1
(
false­
positive)
and
type
2
(
falsenegative
errors.
EPA
also
should
clarify
the
objective
of
the
study
as
this
will
affect
the
measurement
of
successful
validation.

Troy
Seidle,
People
for
the
Ethical
Treatment
of
Animals
In
regard
to
question
1,
Mr.
Seidle
commented
that,
in
principle,
EPA
should
evaluate
the
sensitivity
of
a
two­
generation
design
over
the
existing
standard
practice.
EPA
must
be
able
to
demonstrate
a
significant
need
as
well
as
"
value
added"
before
a
new
test
or
endpoint
is
considered
as
a
regulatory
requirement.
That
being
said,
EPA's
current
requirement
for
a
multiplicity
of
animal
tests
for
the
same
or
similar
endpoints
is
redundant
and
unacceptable.
As
a
matter
of
policy,
EPA
program
offices
must
better
coordinate
their
chemical
assessment
efforts
in
order
to
prevent
duplication.
Mr.
Seidle
said
that
in
regard
to
question
2,
from
a
strictly
scientific
perspective,
the
answer
is
yes,
because
it
would
be
unwise
to
assume
that
data
from
one
species
are
generalizable
to
another.
On
a
policy
level,
however,
it
would
be
inappropriate
for
EPA
to
proceed
into
prevalidation
of
a
test
of
this
magnitude
with
four
species;
a
single
species
is
more
than
enough.
In
conclusion
Mr.
Seidle
asked
that
immediate
consideration
be
given
to
reducing
the
scope
of
Tier
2
to
the
single
most
sensitive
species,
and
discontinuing
efforts
to
develop
and
validate
multigenerational
studies
in
others.

V
.
Next
Steps
Dr.
Touart
summarized
some
of
the
comments
he
heard
from
the
EDMVS
members:

EPA
should
evaluate
whether
the
two­
generation
protocol
is
sufficient
and
should
consider
multigenerational
protocol
in
order
to
cover
exposure
potential
for
eggs
and
embryos.

Species
comparisons
within
the
two­
generation
method
would
be
useful,
as
would
comparisons
to
show
the
advantages
of
this
protocol
over
lifecycle,
partial
lifecycle,
and
multigeneration
tests.
14

EPA
should
consider
geopolitical
preferences
in
choosing
a
test
species.
A
comparison
across
species
would
be
valuable.

The
aqueous
exposure
route
seems
most
relevant.
The
DRP
should
include
a
discussion
of
the
circumstances
under
which
other
exposure
routes
might
be
used.

Mr.
De
Morgan
thanked
Dr.
Touart
for
his
presentation
and
others
for
their
comments
and
discussion.
Mr.
Merenda
also
thanked
the
members
for
the
productive
discussion.
Noting
that
Ms.
Smith
was
about
to
present
the
proposed
meeting
schedule,
he
asked
members
to
remember
that
EPA
is
striving
to
balance
the
desire
for
momentum
with
the
reality
of
needing
to
have
information
ready
for
each
meeting
in
order
to
use
members'
time
as
efficiently
as
possible.

Mr.
De
Morgan
asked
members
whether
they
felt
the
call
had
given
them
adequate
time
to
discuss
the
DRP.
Several
members
noted
they
had
additional
comments
and
could
have
used
more
time
for
the
discussion.
Some
said
they
would
submit
written
comments
to
Ms.
Smith.
Dr.
Touart
noted
that
comments
would
be
most
useful
if
they
were
received
by
January
10,
2003.
Mr.
De
Morgan
suggested
that
EPA
should
review
the
comments
and
then
consider
whether
it
would
be
beneficial
to
hold
a
second
conference
call
or
include
further
discussion
of
this
DRP
on
the
agenda
of
a
future
inperson
meeting.

Proposed
Future
Meeting
Schedule
Ms.
Smith
presented
the
following
proposed
meeting
schedule
and
asked
members
to
reserve
the
dates,
noting
that
the
topics
for
each
meeting
are
still
tentative.

June
4­
5,
2003
(
2
full
days)
o
June
4
­
Mammalian
2­
generation
(
Tier
II):
One
generation
extension
study
results;
Avian
Two
Generation
Assay
(
Tier
II)
Detailed
Review
Paper
o
June
5
 
Steroidogenesis
Assay
(
Tier
I):
The
Results
of
the
Optimization
of
the
Protocol
using
sliced
testes
;
Aromatase:
The
results
of
the
optimization
and
performance
comparison
of
the
assay
using
placental
tissues
(
porcine,
human,
bovine)
and
human
recombinant
receptor

August
19­
21,
2003
(
2
1/
2
days)
o
Aug
19
(
half
day)
­
Fish
Short
Term
Reproduction
Assay
(
Tier
I):
Evaluation
of
Vitellogenin
Methods
in
Zebrafish
&
Medaka
study
results;
Fish
Reproductive:
Evaluation
of
Vitellogenin
Methods
in
Fathead
Minnow
study
results
o
Aug
20
­
Fish
Short
Term
Reproduction
Assay
(
Tier
I):
Comparative
Evaluation
of
the
Fathead
Minnow
Assays
study
results
o
Aug
21
­
Pubertals
male
and
female:
Multi­
dose
demonstration
study
results;
Pubertals
male
and
female:
Multi­
chemical
Array
study
results
The
meeting
was
adjourned
at
noon.
15
Attachment
A
Non­
Members
Who
Joined
by
Phone
Gary
Ankley,
EPA
Karin
Bentley,
DuPont
Crop
Protection
Ron
Biever,
SpringbornSmithers
Laboratories
Michael
Blanton,
Battelle
Karen
Bredam
Scott
Brown,
National
Water
Research
Institute
Kristen
Brugger,
Crop
Life
of
America
Ralph
Cooper,
EPA
Paul
De
Morgan,
RESOLVE
Norma
Domey,
Environment
Canada
Beth
Doyle,
EPA
Reinhart
Fischer,
Bayer
Crop
Science
Jerry
Goldman,
EPA
Tilghman
Hall,
Bayer
Corporation
Charles
Harper
Kevin
Henry
Gary
Henshaw
Dave
Houchens,
Battelle
Jerry
Johnson,
Battelle
Susan
Laws,
EPA
Ellen
Mahaich,
Rhodia
Miriam
Medina­
Vera,
EPA
Claudia
Olivieri,
BASF
Troy
Seidle,
People
for
the
Ethical
Treatment
of
Animals
Ann
Skillman,
Battelle
Tim
Springer,
Wildlife
International
Tammy
Stoker,
EPA
Non­
Members
Who
Joined
the
Meeting
at
the
RESOLVE
Conference
Room,
Washington,
DC
Elaine
Francis,
EPA
Rick
Becker,
American
Chemistry
Council
Sue
Euling,
EPA
Sally
Grady,
EPA
Jim
Kariya,
EPA
Sara
Litke,
RESOLVE
Rich
Liroff,
World
Wildlife
Fund
Joe
Nash,
EPA
Kazuhiko
Nishroka,
Japan
External
Trade
Organization
Jennifer
Peyser,
RESOLVE
Greg
Schweer,
EPA
16
Jane
Smith,
EPA
Kris
Thayer,
Environmental
Working
Group
Gary
Timm,
EPA
Les
Touart,
EPA
Phil
Zahodiakin,
CRC
Press,
Pesticide
and
Toxic
Chemical
News