Document ID: EPA-HQ-OPPT-2003-0010-0018
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-03-11T05:00Z

Task
Force
February
12,
2003
Mr.
Wardner
C.
Penberthy
Director,
Chemical
Control
Division
U.
S.
EPA
OPPTS
{
7405M]
1200
Pennsylvania
Ave.
N.
W.
WashingtonDC
20460
P.
O.
Box
331,
Mil~
wood,
VA
22646
(
540)
837­
1602
RE:
Consent
Agreement
for
Ethylene
Dichloride
Dear
Mr.
Penberthy:

I
have
initialed
the
correction
on
the
enclosed
page
6
ofthe
ECA
for
ethylene
dichioride
regarding
"
Gargas
et
al.
(
1987;
1988)"
to
DiSouza
et
al.
(
1987;
1988)"
as
requested.
Also,
minor
additions
were
made
to
Appendix
C
of
the
ECA
that
included
a
reaction
diagram
and
a
reference
list.
These
additions
have
been
provided
to
John
Schaeffer.

Enclosure
cc:
John
Schaeffer
(
w/
o
end.)
Rich
Leukroth
(
w/
o
end.)
Caffey
Norman
(
w/
o
end.)
Yours
truly,

Peter
Voytek,
PhD
HAP
Task
Force
Manager
RECEIVED
OPPT
NCIC
2003
MAR11
5:
03PM
OPPT­
2003­
0010­
0018
VI.
DESCRIPTION
OF
THE
TESTING
PROGRAM
The
testing
program
has
four
segments
as
follows:
Tier
I
HAPs
Testing;
Tier
I
Program
Review
Testing;
EPA
Program
Review;
and
Tier
II
Testing.

A.
Tier
I
HAPs
Testing:
This
testing
will
consist
of
the
following
endpoint
testing,
conducted
by
inhalation
exposure,
that
EPA
has
deemed
necessary
to
meet
certain
data
needs
identified
in
the
proposed
HAPs
test
rule,
as
amended:
I)
acute
toxicity
testing
with
BAL
and
histopathology,
and
2)
acute
neurotoxicity
testing.
EPA
will
not
finalize
the
testing
requirements
for
these
Tier
I
HAPs
Testing
endpoints
for
ethylene
dichloride
as
specified
in
the
proposed
HAPs
test
rule,
as
amended,
because
such
testing
will
be
conducted
under
this
ECA.
Furthermore,
EPA
considers
the
existing
study
by
Sherwood
et
at.
(
1987),
adequate
to
fulfill
the
macrophage
function
assay
portion
of
the
acute
toxicity
testing
requirement
(
see
Appendix
E.
1).
In
addition,
EPA
considers
the
existing
studies
by
Rao
et
at.
(
1980)
and
Payan
et
at.
(
1995),
adequate
to
characterize
the
developmental
toxicity
of
ethylene
dichioride
under
the
proposed
HAPs
rulemaking,
as
amended
(
see
Appendix
E.
3).
Thus,
EPA
will
not
finalize
the
testing
requirements
for
the
developmental
toxicity
and
macrophage
function
assay
Tier
I
HAPs
testing
endpoints
for
EDC
as
specified
in
the
HAPs
proposed
rule
as
amended,
because
available
studies
are
acceptable
for
HAPs
purposes.
Tier
1
testing
for
acute
toxicity
and
acute
neurotoxicity
and
the
extant
data
for
macrophage
function
assay
and
developmental
toxicity
testing
are
specified
in
the
`
Tier
I
HAPs
Testing'
segment
of
Table
1
and
described
in
Appendix
B(
1,2)
as
annotated
in
Appendix
D(
1),
and
Appendix
E(
1,3).

B.
Tier
I
Program
Review
Testing:
This
testing,
specified
in
the
"
Tier
I
Program
Review
Testing"
segment
of
Table
1
and
described
in
Appendix
C.
1,
will
develop
PK/
MECH
data
needed
to
inform
about
the
acceptability
of
an
alternate
route
to
inhalation
for
Tier
II
testing.
It
will
also
develop
and
validate
the
dosimetry
model
of
~
a~
gaset
at.
(
1987;
1988)
in
rats
and
verify
the
ability
of
the
model
to
perform
quantitative
route­
to­
route
extrapolations,
as
described
in
Appendix
C(
2­
5)
and
as
will
be
reported
following
guidance
provided
in
Appendix
C.
6.
Data
from
this
testing
will
be
the
subject
of
discussions
at
the
EPA
Program
Review.
While
EPA
believes
that
it
is
best
to
obtain
this
type
of
PK/
MECH
data
in
conjunction
with
the
testing
specified
in
the
Tier
I
HAPs
Testing
(
see
Part
VI.
A.),
these
PKIMECH
data
may
also
be
obtained
independently
from
stand­
alone
studies.
Specifically,
the
PKJMECH
data
will
support:
1)
oral­
to­
inhalation
extrapolation
of
existing
subchronic
toxicity
data
in
rats
administered
ethylene
dichloride
via
corn
oil
gavage
(
Daniel
et
at.,
1994)(
see
Appendix
E.
2);
2)
oral­
toinhalation
extrapolation
of
subchronic
neurotoxicity
data
in
rats
administered
ethylene
dichloride
via
drinking
water
(
see
Tier
H
testing);
and
3)
oral­
to­
inhalation
extrapolation
of
reproductive
toxicity
data
in
rats
administered
ethylene
dichloride
via
drinking
water
(
see
Tier
II
testing)
and
each
dosing
paradigm
of
existing
reproductive
toxicity
studies
by
Alumot
et
al.
(
1976),
Rao
et
at.
(
1980),
and
Lane
et
at.
(
l982)(
see
Appendix
E.
4).
The
PKJMECH
data
will
also
support
model
simulations
to
demonstrate
validation
and
verification
of
PBPK
models
for
route­
to­
route
extrapolation
in
order
to
evaluate
acceptability
of
oral
drinking
water
exposure
in
rats
in
the
Tier
II
testing
for
subchronic
neurotoxicity
and
reproductive
toxicity.

6