Document ID: EPA-HQ-OPP-2004-0202-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-07-29T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
DATE:
October
31,
2001
SUBJECT:
Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
Held
on
10/
04/
01
to
discuss
PCNB
technical
materials
from
Uniroyal
and
Amvac
(
10/
4/
01).
Chemical
056502.

FROM:
Sheila
Piper,
Chemist
Diana
Locke,
Toxicologist
Health
Effects
Division
(
7509C)

THROUGH:
Francis
B.
Suhre,
Branch
Senior
Scientist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C)
and
Christine
Olinger,
Chair
of
HED
MARC
Reregistration
Branch
I
Health
Effects
Division
(
7509C)

TO:
Yan
W.
Donovan,
Chemist,
RAB1/
HED
(
7509C)
MARC
Executive
Secretary
Material
Reviewed
The
Metabolism
Assessment
Review
Committee
(
MARC)
met
on
October
4,
2001
to
determine
if
the
variability
in
the
level
of
active
ingredient
of
PCNB
and
its
contaminants
in
the
Uniroyal
and
Amvac
test
materials
used
for
toxicity
studies
is
significant
enough
to
call
into
question
current
registrations
for
the
Uniroyal
and
Amvac's
PCNB
technical
grade
of
active
ingredients.
The
Committee
also
discussed
the
concern
that
some
of
the
contaminants
or
combinations
of
contaminants
found
in
the
Uniroyal
and
Amvac's
PCNB
TGAIs
that
may
be
of
toxicological
concern
and
would
trigger
additional
risk
assessments
and/
or
data
requirements.
Page
­
2­
The
MARC
conducted
a
side­
by­
side
comparison
of
the
Uniroyal
and
Amvac
submitted
toxicity
data
with
data
on
the
impurities
by
using
the
following
approach.
The
registrants
had
submitted
batch
numbers
and
formulation
information,
including
the
trace
amount
(
relative
weight
basis)
of
manufacturing
impurities
that
are
of
toxicological
concern.
A
literature
search
was
conducted
for
toxicity
data
on
the
impurities
and
therefore,
the
MARC
had
some
information
about
the
toxic
effects
induced
by
the
impurities
and
the
levels
(
LOAELs)
at
which
these
effects
were
seen.
With
the
submitted
batch
information,
the
MARC
was
able
to
calculate
the
amount
of
each
impurity
that
was
administered
in
the
toxicity
studies,
along
with
the
PCNB.
Both
the
toxic
effects
and
the
effective
doses
of
the
impurities
were
compared
with
the
effects
observed
in
the
PCNB
studies
and
the
administered
doses
of
the
impurities.
It
should
be
noted
that
in
1994,
the
Agency
informed
Uniroyal
and
Amvac
of
the
need
to
reduce
the
relative
amount
of
HCB
in
their
technical
formulations
to
0.05
%
and
the
amount
of
pentachlorobenzene
(
PCB)
to
0.01
%
(
Letter.
Jack
Housenger.
October
4,
1994).

The
formulations
of
the
materials
used
for
the
toxicity
tests,
Amvac's
and
Uniroyal's,
contain
more
than
0.01
%
HCB
(
most
were
greater
than
the
0.05%).
It
would
stand
to
reason
then,
that
by
using
the
submitted
toxicity
data
for
endpoint
selection,
the
Agency
would
be
conservative
in
its
health
protective
approach
and
would
not
be
underestimating
the
potential
risks.
In
addition,
in
a
written
communication
from
the
Agency's
Office
of
General
Counsel
(
OGC),
the
Health
Effects
Division
(
HED)
was
informed
that
HED
science
reviewers
may
review
studies
submitted
by
one
registrant
in
connection
with
an
EPA
registration/
reregistration
action
for
another
registrant
[
Communication.
Mark
Dyner
(
OGC)
to
Beth
Doyle
(
HED).
November
1,
2000].
It
went
on
to
say
that
EPA
scientists
can
and
should
look
at
all
relevant
data
in
the
Agency's
files
when
making
decisions.

MARC
Conclusions
The
MARC
can
find
no
evidence
that
the
chemical
composition
(
i.
e.
impurity
levels)
differences
among
the
formulations
tested
in
the
toxicity
studies
affected
the
NOAELS/
LOAELS
and
endpoints
found.
Other
factors
likely
were
greater
contributors
to
the
differences
in
the
side­
by­
side
toxicity
studies
submitted
by
the
two
registrants.
Furthermore,
it
is
the
MARC's
opinion
that
the
contaminants
at
the
level
found
in
the
tested
batches
and
the
Page
­
3­
Cl
Cl
Cl
Cl
Cl
NO
2
Cl
Cl
Cl
Cl
Cl
Cl
levels
mandated
by
the
Agency
in
the
12/
94
letter
will
not
bias
the
results
of
the
toxicity
studies.

Individuals
in
Attendance
1.
MARC
Members
Alberto
Protzel,
Christine
Olinger,
Rick
Loranger,
Leung
Cheng,
John
Doherty,
Yan
Donovan,
Abdallah
Khasawinah,
David
Nixon,
Thuy
Ngnyen
and
Sheila
Piper.

2.
Scientists
(
non­
MARC
members)

Francis
Suhre(
CEB),
Mike
Ioannou(
TOX1),
Lucy
Shanaman(
EFED),
Ken
Dockter
(
RRB1)
and
Diana
Locke
(
RRB1).

cc:
SF,
RF,
List
B
File,
S.
Piper,
D.
Locke
(
RRB1)
RDI:
C.
Olinger:
10/
17/
01;
F.
B.
Suhre:
10/
18/
01
7509C:
CEB1:
CM­
2:
Room
810F:
308­
2717:
PCNB
Table
1:
Structures
of
PCNB
and
metabolites
Chemical
Name/
Structure
Pentachloronitrobenzene
(
PCNB)
Hexachlorobenzene
(
HCB)
Page
­
4­
Cl
Cl
Cl
Cl
Cl
C
H
3
N
H
O
CH
3
NO
2
Cl
4
Cl
Cl
Cl
Cl
Cl
NH
2
Pentachlorobenzene
(
PCB)
N,
N­
dimethylformamide
Tetrachoronitrobenzene
(
TCNB)
Pentachloroaniline
(
PCA)