UNITED
STATES
ENVIRONMENTAL
PROTECTIGN
AGENCY
WASHINGTON,
D.
C.
20460
/­
j/­.
(­
J,
r:
z
JUN
2
6
1997
z/
s
Mv
OFFICE
Of
PREVENTION.
PESTICIDES
AND
TOXK:
SUBSTANCES
Peter
E.
Voytek,
Ph.
D.
Manager,
HAP
Task
Force
2001
L
Street,
NW
Suite
506A
Washington,
DC
20036
Dear
Dr.
Voytek:

EPA
has
reviewed
the
two
alternative
PK
testing
proposals
submitted
by
the
HAP
Task
Force
on
November
22,
1996.
These
proposals
are
entitled
"
Proposal
for
Pharmacokinetics
Study
of
Ethylene
Dichloride"
and
"
Proposal
for
Pharmacokinetics
Study
of
1,1,2­
Trichloroethane."

These
proposals
were
prepared
in
response
to
EPA's
invitation
for
proposals
for
pharmacokinetics
(
PK)
studies
for
the
hazardous
air
pollutants
(
HAPS)
listed
in
the
proposed
test
rule
for
HAPS
(
61
FR
33
178;
June
26,1996).
The
PK
studies
would
be
used
to
inform
the
Agency
about
route­
to­
route
extrapolation
of
toxicity
data
from
routes
other
than
inhalation
when
it
is
scientifically
defensible
in
order
to
empirically
derive
the
inhalation
risk.
The
PK
proposals
could
form
the
basis
for
negotiation
of
enforceable
consent
agreements
(
ECAs)
that
would
provide
for
testing
in
lieu
of
some
or
all
of
the
tests
proposed
in
the
HAPS
rule.

The
following
provides
a
background
to
EPA's
method
of
evaluating
the
proposed
PK
strategies.
As
you
recall,
in
the
preamble
to
the
proposed
test
rule,
EPA
indicated
that,
when
reviewing
PK
proposals,
it
would
use
the
Gerrity
and.
Henry
(
1990)
decision
tree
as
an
element
in
evaluating
the
proposed
PK
studies.
The
Agency
also
indicated
that
it
would
use
mechanistic
data
in
determining
the
appropriateness
of
route­
to­
route
extrapolation
of
the
existing
data
base
as
an
alternative
to
conducting
some
or
all
of
the
testing
required
under
the
proposed
HAPS
test
rule.
Pharmacokinetics
and
mechanistic
data
may
be
used
to
inform
the
Agency
about
route­
to­
route
extrapolation
when
EPA
determines
that
extrapolation
from
existing
studies
may
provide
sufficient
data
to
substitute
for
required
testing
under
the
proposed
rule.
Pharmacokinetics
and
mechanistic
data
alone
may
not
be
used
to
substitute
for
proposed
required
testing
when
studies
by
a
route
other
than
inhalation
do
not
exist
or
are
deemed
by
EPA
to
be
inadequate.
In
such
cases,
however,
pharmacokinetics
and
mechanistic
data
may
be
used
to
support
a
decision
that
required
testing
could
be
conducted
using
routes
other
than
inhalation.

R*
cycled/
Flc
63978884785
100%
Recychd
Paper
(
40%
Poslmnsumer)
RECEIVED
OPPT
NCIC
2003
MAR11
5:
08PM
OPPT­
2003­
0010­
0035
­,
.
.

2
EPA
has
concluded
that
the
strategies
described
in
the
proposals
for
ethylene
dichloride
(
EDC)
and
1
.1,2­
trichloroethane
(
TCE)
offer
sufficient
technical
merit
to
warrant
further
consideration.
The
Agency
invites
the
HAP
Task
Force
to
consider
EPA'S
preliminary
technical
analyses
of
these
proposals,
copies
of
which
are
enclosed
in
this
letter.
Please
note
that
these
analyses,
including
all
discussions
concerning
data
adequacy
and
test
procedures/
methods
pertain
only
to
the
adequacy
of
PK
proposal
for
its
intended
purpose
and
not
to
the
statutory
basis
for
issuing
the
HAPS
rule
under
section
4
of
the
Toxic
Substances
Control
Act
(
TSCA).

If,
after
the
HAP
Task
Force
has
had
the
opportunity
to
review
these
analyses,
you
have
a
continued
interest
in
pursuing
the
ECA
process
for
either
or
both
chemicals
as
an
activity
distinct
from
the
test
rule
process,
please
respond
to
me
in
writing
by
July
3
1,
1997.
Depending
on
the
Panel's
response,
EPA
will
determine
whether
or
not
to
proceed
with
the
ECA
process
for
either
or.
both
chemicals.
(
The
procedures
for
ECA
negotiations
are
described
at
40
CFR
790.22(
b).)
Under
this
process,
EPA
would
publish
a
notice
in
the
Federal
&
g&&
soliciting
interested
parties
to
participate
in
or
monitor
negotiations
for
an
ECA
on
EDC
and
TCE.
The
notice
will
also
announce
a
date
for
a
public
meeting
to
negotiate
the
ECA.
At
these
negotiations
EPA
may
raise
issues,
based
on
the
Agency's
further
review
of
the
proposed
strategy,
that
differ
from
those
contained
in
the
preliminary
technical
analysis.
EPA
notes
that,
as
a
result
of
unexpected
complexities
arising
in
the
review
of
the
proposals
and
contrary
to
the
statement
in
the
preamble
to
the
proposed
HAPS
test
rule,
the
Agency
will
not
be
able
to
conclude
ECAs
within
12
months
of
the
date
of
the
HAPS
proposal.

The
documents
submitted
by
the
HAP
Task
Force
went
beyond
PK
by
including
an
alternate
testing
strategy
for
each
chemical
to
respond
to
the
proposed
testing
identified
in
the
proposed
HAPS
test
rule.
EPA's
evaluations
of
these
proposals
identify
changes
or
additions
that
provide
for
testing
of
EDC
and
TCE
as
an
alternative
to
the
testing
contained
in
the
proposed
HAPS
test
rule.
If
this
testing
is
incorporated
into
ECAs
that
are
successfully
conciuded
between
EPA
and
the
HAP
Task
Force,
and
if
the
data
resulting
from
testing
under
the
ECAs
are
acceptable
to
the
Agency,
such
testing
will
provide
an
alternative
to
some
or
all
of
the
testing
proposed
for
EDC
and
TCE
in
the
HAPS
test
rule.
If
testing
under
these
ECAs
does
not
fulfill
the
Agency's
needs,
EPA
reserves
the
right
to
meet
these
needs
through
rulemaking.

EPA
notes
that
the
HAP
Task
Force
makes
certain
assumptions
regarding
the
interpretation
and
use
of
the
available
toxicological
database
for
chemicals
with
similar
physicochemical
characteristics
as
EDC
and
TCE.
The
testing
requirements
for
EDC
and
TCE
in
the
proposed
HAPS
test
rule
were
identified
by
EPA
for
the
purpose
of
providing
a
database
to
permit
the
assessment
of
residual
risk
following
the
implementation
of
the
maximum
achievable
control
technology
(
MACT)
standards
required
by
the
Clean
Air
Act.
EPA
must
apply
rigorous
standards
to
determine
the
adequacy
of
studies
to
be
used
for
route­
to­
route
extrapolation.
_
Although,
as
stated
earlier
in
this
letter;
EPA
considers
its
current
analysis
of
the
studies
cited
in
the
EDC
and
TCE
PK
Proposals
to
be
preliminary,
the
Agency
will
be
prepared
to
discussall
issues
in
detail
with
the
members
of
the
HAP
Task
Force
if
the
Agency
decides
to
proceed
with
the
ECA
process.
i
,,._

il
3
It
is
important
that
member
companies
of
the
HAP
Task
Force
recognize
the
importance
of.
responding
to
the
request
for
comments
on
the
proposed
HAPS
rule.
The
submission
of
PK
proposals
to
develop
ECAs
to
conduct
testing
alternative
to
that
contained
in
the
HAPS
test
rule
is
no
guarantee
that
EPA
and
the
HAP
TaskForce
will,
in
fact,
conclude
such
agreements.
Therefore,
I
urge
the
companies
to
submit
comments
on
the
proposed
HAPS
rule
as
an
activity
separate
from
the
ECA
process.
Please
submit
three
copies
of
written
comments
on
the
proposed
HAPS
test
rule,
identified
by
document
control
number
(
OPPTS42187A;
FRL­
4869­
1)
to:
U.
S.
Environmental
Protection
Agency,
Office
of
Pollution
Prevention
and
Toxics,
Document
Control
Office
(
7407),
Rm.
G­
099,401
M
St.,
SW,
Washington,
DC
20460.

In
sum,
EPA
would
like
to
thank
the
HAP
Task
Force
for
its
initial
proposal$.
If
you
have
any
technical
questions
about
EPA"
s
comments
on
your
proposals,
please
contact
Annie
Jarabek
at
(
9
19)
541­
4847
(
voice),
(
9
19)
541­
I
8
18
(
fax),
or
jarabek.
annie@
epamail.
epa.
gov
(
e­
mail).
For
questions
about
the
ECA
process,
please
contact
Richard
Leukroth
at
(
202)
260­
032
1
(
voice),
(
202)
260­
8850
(
fax),
or
leukroth.
rich@
epamail.
epa.
gov
(
email).

Sincerely,

Charles
M.
Auer
Director
Chemical
Control
Division
Enclosures
­­
_­­.
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