Document ID: EPA-HQ-OAR-2004-0074-0103
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-01-14T05:00Z

April
29,
2003
Donald
R.
Lynam
Vice
President,
Air
Conservation
Ethyl
Corporation
330
South
Fourth
Street
Richmond,
VA
23219­
4304
Dear
Dr.
Lynam,

On
February
28,
2003,
you
submitted
to
the
Environmental
Protection
Agency
(
EPA),
on
behalf
of
Ethyl
Corporation
(
Ethyl),
a
peer­
reviewed
draft
study
report
entitled:
"
Pharmacokinetics
of
Inhaled
Manganese
Sulfate
in
Pregnant
and
Lactating
CD
Rats,"
(
CIIT
Protocol
01003).
This
pharmacokinetics
(
PK)
study
is
part
of
the
requirements
finalized
in
the
notification
letter
received
by
Ethyl
on
May
25,
2000.
As
you
know,
the
notification
letter
requires
that
EPA
provide
comments
on
peer­
reviewed
draft
study
reports.
Also,
on
April
2,
2003,
on
behalf
of
Ethyl,
you
requested
amendments
to
the
study
protocol
entitled,
"
Pharmacokinetics
of
Manganese
Sulfate
in
Juvenile
Male
Rhesus
Monkeys
following
sub­
chronic
(
13­
week)
Inhalation
Exposure,"
(
CIIT
Protocol
02005).
This
letter
addresses
both
of
these
issues.

Regarding
the
peer­
reviewed
draft
study
report
on
the
PK
study
in
pregnant
and
lactating
rats,
the
conclusions
presented
seem
to
be
supported
by
the
results
of
the
study.
Additionally,
the
study
report
adequately
addresses
the
peer
reviewer
concerns
and
we
have
no
additional
comments.

Regarding
your
April
2,
2003,
letter,
you
requested
two
major
amendments,
as
well
as
four
other
minor
amendments,
for
the
PK
study
in
rhesus
monkeys,
CIIT
Protocol
02005.
First,
you
requested
a
three­
month
extension
to
the
required
schedule
for
submission
to
the
Agency
of
the
draft
final
peer­
reviewed
report
for
this
study.
Since
this
study
is
complex
in
nature,
and
involves
peer­
review
by
the
Technical
Advisory
Panel
(
TAP),
we
believe
your
request
for
a
three­
month
extension
to
the
required
schedule
for
this
study
is
reasonable,
and
is
therefore
granted.
­
2­

Second,
you
requested
an
amendment
to
the
protocol
to
allow
for
the
addition
of
magnetic
resonance
imaging
(
MRI)
to
the
PK
study
in
rhesus
monkeys,
CIIT
Protocol
02005.
The
Agency
supports
these
additional
MRI
evaluations
of
primates
in
this
study,
and
believes
the
inclusion
of
MRI
will
add
substantial
value
to
this
study.

The
four
other
amendments
requested
in
your
April
2,
2003,
letter
include
storage
and
use
of
manganese
sulfate
at
room
temperature
which
would
adhere
to
updated
labeling
and
Material
Safety
Data
Sheet
information;
the
collection
of
additional
drinking
water
samples;
the
measurement
of
body
weights
whenever
possible,
rather
than
as
originally
specified
due
to
problems
in
moving
the
animals
to
transfer
cages;
and
the
addition
of
trachea
and
larynx
tissue
collection
during
necropsy.
We
believe
these
requested
changes
will
not
significantly
impact
the
goals
of
the
study
and
through
this
letter
we
also
approve
these
four
protocol
amendment
requests.

We
look
forward
to
Ethyl's
submission
of
the
final
PK
study
report
in
pregnant
and
lactating
rats,
as
well
as
Ethyl's
completion
of
the
PK
study
in
rhesus
monkeys.
If
you
have
any
questions
concerning
our
review,
please
contact
Joe
Sopata
of
my
staff
at
(
202)
564­
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
Tim
Backstrom,
OGC
Kevin
Fast,
Hunton
&
Williams