June
28,
2002
Donald
R.
Lynam
Vice
President,
Air
Conservation
Ethyl
Corporation
330
South
Fourth
Street
Richmond,
VA
23219­
4304
Dear
Dr.
Lynam,

On
June
12,
2002,
you
submitted
to
Joe
Sopata
of
my
staff
a
request
for
amendments
to
the
protocol
developed
by
the
Chemical
Industry
Institute
of
Toxicology
(
CIIT)
entitled,
"
Pharmacokinetics
of
inhaled
manganese
sulfate
in
pregnant
and
lactating
CD
rats",
Protocol
01003.
As
you
know,
the
MMT
Alternative
Tier
2
Health
Effects
Testing
Requirements
require
Agency
approval
of
amendments
to
a
previously
approved
protocol.
This
protocol
was
approved
by
the
Agency
on
October
26,
2001.

In
your
request
for
amendments
to
this
protocol
you
said
CIIT
observed
a
significant
number
of
animals
with
calculi
in
the
urinary
tract
but
that
the
incidences
of
calculi­
associated
lesions
were
similar
for
controls
and
for
the
manganese
exposure
groups.
You
also
noted
that
a
CIIT
background
document
stated
that
the
presence
of
calculi
is
not
manganese
treatment
related
and
has
been
observed
by
other
investigations
using
the
diet
specified
in
the
protocol.
CIIT
requested
an
amendment
to
the
protocol
to
allow
for
replacement
animals
to
be
included
in
the
studies
to
account
for
animals
which
had
to
be
removed
from
the
study
due
to
these
urinary
tract
problems.
The
inclusion
of
replacement
animals
would
help
to
maintain
adequate
group
sample
sizes.
CIIT
also
requested
amendments
to
the
protocol
to
include
additional
testing
facilities
and
studies
related
to
evaluation
of
calculi
found
in
the
urinary
tract
of
control
and
manganese
exposed
animals.
Finally,
you
requested
minor
changes
in
the
description
of
protocol
methods
to
more
accurately
describe
the
exposure
system
used
in
the
protocol.

This
letter
conveys
the
Agency's
approval
of
your
requested
amendments
to
CIIT
Protocol
01003,
so
long
as
any
replacement
animals
receive
their
full
scheduled
exposures
and
records
are
maintained
and
reported
regarding
the
experimental
conditions
and
history
of
any
original
and
replacement
animals.
­
2­

If
you
have
any
questions,
please
contact
Joe
Sopata
of
my
staff
at
(
202)
564­
9034.

Sincerely,

/
s/

Robert
E.
Larson,
Acting
Director
Transportation
and
Regional
Programs
Division
cc:
Monica
Alvarez,
ORD/
OSP
Tim
Backstrom,
OGC
Kevin
Fast,
Hunton
&
Williams
