Document ID: EPA-HQ-OPPT-2002-0059-0015
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-04-20T04:00Z

Comments
on
Proposed
Fish
Comments
on
Proposed
Fish
Two
Two­­
Generation
Toxicity
Test
Generation
Toxicity
Test
Endocrine
Disruptor
Methods
Validation
Subcommittee
Endocrine
Disruptor
Methods
Validation
Subcommittee
December
4,
2002
December
4,
2002
Troy
Troy
Seidle
Seidle
Science
Policy
Advisor
Science
Policy
Advisor
People
for
the
Ethical
Treatment
of
Animals
People
for
the
Ethical
Treatment
of
Animals
OPPT­
2002­
0059­
0015
RECEIVED
OPPT
NCIC
2003
MAR19
2:
49PM
Should
Should
prevalidation
prevalidation
evaluate
the
increased
sensitivity
evaluate
the
increased
sensitivity
of
a
two
of
a
two­
generation
design
over
the
existing
fish
full
generation
design
over
the
existing
fish
full
life
life­
cycle
standard
practice?

cycle
standard
practice?

In
principle,
yes.
EPA
must
be
able
to
demonstrate
a
In
principle,
yes.
EPA
must
be
able
to
demonstrate
a
significant
need
as
well
as
"
value
added"
before
a
new
test
significant
need
as
well
as
"
value
added"
before
a
new
test
and/
or
endpoint
is
considered
as
a
regulatory
requirement.

and/
or
endpoint
is
considered
as
a
regulatory
requirement.

That
being
said,
EPA's
current
requirement
for
a
multiplicity
of
That
being
said,
EPA's
current
requirement
for
a
multiplicity
of
animal
tests
for
the
same
or
similar
endpoint(
s)
is
redundant
animal
tests
for
the
same
or
similar
endpoint(
s)
is
redundant
and
unacceptable
and
unacceptable
e.
g.,
pesticide
AI's
that
have
already
undergone
fish
full
life
e.
g.,
pesticide
AI's
that
have
already
undergone
fish
full
life­
cycle,

cycle,

mammalian
2
mammalian
2­
gen
gen.
studies,
etc.,
and
HPV
chemicals
that
are
currently
.
studies,
etc.,
and
HPV
chemicals
that
are
currently
undergoing
1
undergoing
1­
gen
gen.
repro/
developmental
studies,
potentially
being
.
repro/
developmental
studies,
potentially
being
required
to
undergo
very
similar
studies
under
the
EDSP.

required
to
undergo
very
similar
studies
under
the
EDSP.

Therefore,
as
a
matter
of
policy,
EPA
program
offices
must
Therefore,
as
a
matter
of
policy,
EPA
program
offices
must
better
coordinate
their
chemical
assessment
efforts
in
order
to
better
coordinate
their
chemical
assessment
efforts
in
order
to
prevent
such
obvious
duplication.

prevent
such
obvious
duplication.
Should
Should
prevalidation
prevalidation
demonstrate
the
sensitivity
and
demonstrate
the
sensitivity
and
reproducibility
for
each
species
in
the
recommended
reproducibility
for
each
species
in
the
recommended
protocol?

protocol?

From
a
strictly
scientific
perspective,
yes,
because
it
would
be
From
a
strictly
scientific
perspective,
yes,
because
it
would
be
unwise
to
simply
assume
that
data
from
one
species
are
unwise
to
simply
assume
that
data
from
one
species
are
generalizable
generalizable
to
another.

to
another.

On
a
policy
level,
however,
it
would
be
inappropriate
for
EPA
to
On
a
policy
level,
however,
it
would
be
inappropriate
for
EPA
to
proceed
into
proceed
into
prevalidation
prevalidation
of
a
test
of
this
magnitude
with
four
of
a
test
of
this
magnitude
with
four
species.

species.
A
single
species
is
more
than
enough
A
single
species
is
more
than
enough.
As
the
DRP
.
As
the
DRP
suggests,
"
pre
suggests,
"
pre­
selection
of
one
of
the
four
species 
would
limit
selection
of
one
of
the
four
species 
would
limit
the
number
of
demonstration
trials
for
full
optimization "
(
p.
2
the
number
of
demonstration
trials
for
full
optimization "
(
p.
2)
Issues
of
concern
regarding
the
DRP
Issues
of
concern
regarding
the
DRP
Methodological
limitations
Methodological
limitations
"
full
life
"
full
life­
cycle
exposures 
can
result
in
unexpected
interruptions
in
cycle
exposures 
can
result
in
unexpected
interruptions
in
exposure
as
a
result
of
test
substance
behavior
in
water
or
equi
exposure
as
a
result
of
test
substance
behavior
in
water
or
equipment
pment
malfunction"
(
p.
25)

malfunction"
(
p.
25)

"
continuous
exposure
of
P,
F1
and
juvenile
F2
generations
has
no
"
continuous
exposure
of
P,
F1
and
juvenile
F2
generations
has
not
been
t
been
reported"
(
p.
27;
also
pp.
28
reported"
(
p.
27;
also
pp.
28­
31)

31)

"
methods
of
sexual
differentiation
are
established
for
"
methods
of
sexual
differentiation
are
established
for
zebrafish
zebrafish
and
and
medaka
medaka,
but
are
not
published
for
fathead
minnow
and
,
but
are
not
published
for
fathead
minnow
and
sheepshead
sheepshead
minnow"
(
p.
101)

minnow"
(
p.
101)

Route
of
exposure
Route
of
exposure
Testing
of
poorly
soluble
compounds
in
aquatic
systems
is
highly
Testing
of
poorly
soluble
compounds
in
aquatic
systems
is
highly
questionable.
EPA
itself
has
recommended
against
testing
of
subs
questionable.
EPA
itself
has
recommended
against
testing
of
substances
tances
with
a
log
K
with
a
log
KOW
OW 
4.2
in
fish
because
conditions
of
such
studies
are
both
 
4.2
in
fish
because
conditions
of
such
studies
are
both
biologically
and
toxicologically
irrelevant
(
HPV
Test
Rule,
2000
biologically
and
toxicologically
irrelevant
(
HPV
Test
Rule,
2000,

,
65
Fed
65
Fed
Reg
Reg,
81658
,
81658­
81685)

81685)

Use
of
solvents
to
enhance
exposure
to
hydrophobic
compounds
is
Use
of
solvents
to
enhance
exposure
to
hydrophobic
compounds
is
questionable.

questionable.

Major
identified
confounds
associated
with
oral
exposure
route.

Major
identified
confounds
associated
with
oral
exposure
route.
Issues
of
concern
regarding
the
DRP
Issues
of
concern
regarding
the
DRP
Dose
selection
and
sample
size
Dose
selection
and
sample
size
The
The
DRP's
DRP's
proposed
use
of
"
at
least
five
treatment
levels"
(
p.
30)
is
proposed
use
of
"
at
least
five
treatment
levels"
(
p.
30)
is
excessive
and
should
be
reduced.

excessive
and
should
be
reduced.

The
number
of
replicates
and
control
groups
(
e.
g.,
solvent,
dilu
The
number
of
replicates
and
control
groups
(
e.
g.,
solvent,
dilution
water,

tion
water,

etc.)
should
be
minimized.

etc.)
should
be
minimized.

The
recommended
"
100
embryos
per
replicate"
is
unacceptably
high
The
recommended
"
100
embryos
per
replicate"
is
unacceptably
high
and,

and,

as
the
DRP
acknowledges,
"
twice
the
number
previously
recommende
as
the
DRP
acknowledges,
"
twice
the
number
previously
recommended
by
regulatory
agencies"
(
p.
34).

by
regulatory
agencies"
(
p.
34).
Concluding
thoughts
Concluding
thoughts
EPA's
development
of
two
EPA's
development
of
two­
generation
/
life
generation
/
life­
cycle
toxicity
cycle
toxicity
studies
in
five
separate
taxonomic
groups
is
redundant
and
studies
in
five
separate
taxonomic
groups
is
redundant
and
unnecessary.

unnecessary.

Immediate
consideration
should
be
given
to
reducing
the
Immediate
consideration
should
be
given
to
reducing
the
scope
of
Tier
2
to
the
scope
of
Tier
2
to
the
single
most
sensitive
species
single
most
sensitive
species,
and
,
and
discontinuing
efforts
to
develop
and
validate
multigenerational
discontinuing
efforts
to
develop
and
validate
multigenerational
studies
in
others.

studies
in
others.