Document ID: EPA-HQ-OAR-2004-0074-0132
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-01-14T05:00Z

June
4,
2004
Jerry
M.
Roper,
Ph.
D.
Director,
Air
Conservation
Ethyl
Corporation
330
South
Fourth
Street
P.
O.
Box
2189
Richmond,
VA
23218­
2189
Dear
Dr.
Lynam,

On
March
30,
2004,
you
submitted
to
the
Environmental
Protection
Agency
(
EPA),
on
behalf
of
Ethyl
Corporation
(
Ethyl),
a
draft
peer­
reviewed
final
report
entitled:
"
Pharmacokinetics
of
Manganese
Sulfate
in
Juvenile
Rhesus
Monkeys
Following
Subchronic
(
13­
week)
Inhalation
Exposure."
This
study
addresses,
in
part,
the
requirements
of
the
Alternative
Tier
2
Testing
notification
received
by
Ethyl
on
May
25,
2000
("
the
notification").
This
letter
provides
EPA's
comments
on
this
submission.

EPA
has
found
that
the
pharmacokinetic
(
PK)
study
was
conducted
in
a
manner
consistent
with
the
testing
requirements
required
by
the
notification.
In
addition,
the
peer
review,
conducted
by
the
Technical
Advisory
Panel
(
TAP),
was
very
useful
and
Ethyl's
responses
adequately
addressed
the
peer
review
comments.
The
data
generated
in
this
study
fulfill
the
notification's
requirements
on
primate
PK
studies
and
should
allow
for
development
and
evaluation
of
a
physiologically­
based
PK
model
for
manganese
inhalation,
one
of
the
goals
of
the
testing
required
by
the
notification.

Additionally,
Ethyl
and
EPA
mutually
agreed
to
add
three
additional
measurements
to
the
study
protocols
even
though
they
were
not
required
by
the
notification.
These
included
(
1)
biochemical
assays
of
brain
tissues
from
exposed
animals,
(
2)
T1
magnetic
resonance
imaging
of
the
head
of
selected
animals,
and
(
3)
steady
state
dopamine
concentrations
from
animals
exposed
for
13
weeks.
We
would
be
interested
in
receiving
the
results
of
these
studies
when
they
are
available.
­
2­

We
look
forward
to
Ethyl's
submission
of
the
final
primate
PK
study
report,
as
well
as
the
results
of
the
additional
studies
mentioned
above
when
they
are
available.
If
you
have
any
questions,
please
contact
Joe
Sopata
of
my
staff
at
(
202)
343­
9034.

Sincerely,

/
s/

Suzanne
Rudzinski
Director
Transportation
and
Regional
Programs
Division
cc:
Monica
Alvarez,
ORD/
OSP
J.
Michael
Davis,
ORD/
NCEA
Stan
Durkee,
ORD/
OSP
Hal
Zenick,
ORD/
NHEERL
William
Russo,
ORD/
NHEERL
Steve
Silverman,
OGC
Kevin
Fast,
Hunton
&
Williams