UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
DATE:
May
27th,
2003
SUBJECT:
Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
Held
on
April
16th,
2003
to
discuss
residues
of
concern
in
risk
assessment
and
tolerance
expression
of
Pentachloronitrobenzene
(
PCNB).
Chemical
056502.

FROM:
Mohsen
Sahafeyan,
Chemist,
Reregistration
Branch
2
Laurence
Chitlik,
Toxicologist,
Toxicology
Branch
Health
Effects
Division
(
7509C)

THROUGH:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
2
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
cc:
Diana
Locke,
HED/
RRB2
Individuals
in
Attendance
Members
attended:
Christine
Olinger,
Alberto
Protzel,
Richard
Loranger,
Leung
Cheng,
William
Wassell,
John
Doherty,
Leonard
Keifer,
P.
V.
Shah,
Norman
Birchfield.

Members
in
Absentia:
Yan
Donovan,
Sheila
Piper
Non
Members:
Cheryl
Sutton,
Diana
Locke,
Mohsen
Sahafeyan,
Elizabeth
Doyle,
David
Soderberg,
Laurence
Chitlik
(
conference
call),
George
Kramer
Page
­
2­
Material
Reviewed
The
Metabolism
Assessment
Review
Committee
(
MARC)
met
on
April
16th,
2003
to
determine
the
residues
of
concern
and
the
tolerance
expression
for
plants
and
livestock,
as
well
as
degradates
of
concern
in
water.
The
MARC
reviewed
the
major
and
minor
metabolites
of
pentachloronitrobenzene
(
PCNB)
identified
in
three
plant
metabolism
studies
(
peanuts,
potatoes,
and
cabbage),
livestock
(
ruminant
and
poultry)
metabolism
study,
rotational
crop
studies
(
lettuce,
turnip
roots
and
tops,
and
wheat),
available
field
trial
data,
and
information
on
environmental
persistence
and
degradation
of
PCNB.
The
MARC
also
reviewed
the
available
rat
metabolism
studies.

Plants
and
Rotational
Crops
:
For
the
primary
crops,
plant
metabolism
studies
on
peanuts,
potato,
and
cabbage
[
study
deemed
unacceptable]
indicated
that
the
major
identified
radioactive
residues
(
i.
e.

10%
total
radioactive
residue
or
TRR)
were
PCNB,
S­
(
pentachlorophenyl)
malonycysteine
(
PCP­
MalCys),
N­
malonyl­
S­(
tetrachloroaminophenyl)­
cysteine,
tetrachlorophenyl
methyl
sulfoxide
(
TCPM
sulfoxide),
and
tetrachlorophenyl
methyl
sulfone
(
TCPM
sulfone).
Other
residues
comprising

10%
of
the
TRR
were
not
identified
or
characterized
in
the
cabbage
study.
However,
for
peanut
five
metabolites
and
for
potato
thirty­
six
metabolite
residues
were
identified.
As
all
of
the
identified
plant
metabolites
of
PCNB
in
primary
crops
are
poly­
chlorinated
phenyl
compounds,
all
of
these
compounds
(
including
minor
metabolites)
are
of
concern.

For
rotational
crops,
numerous
metabolites
were
identified
in
just
about
all
crop
parts
studied
in
the
confined
rotational
crop
study.
The
crop
parts
studied
included:
turnip
root
and
tops
from
365
days
after
soil
treatment
(
DAT),
lettuce
(
30,
120,
and
365
DAT),
wheat
forage
(
30
and
120
DAT),
wheat
grain
(
30,
120,
and
365
DAT),
and
wheat
straw
(
120
DAT).
As
all
of
the
identified
metabolites
in
rotational
crops
are
poly­
chlorinated
phenyl
compounds,
all
of
these
compounds
(
including
minor
metabolites)
are
of
concern.

The
residues
of
concern
for
tolerance
setting
purposes
in
primary
and
rotational
crops
are
PCNB,
pentachloraniline
(
PCA),
and
pentachlorothioisole
(
PCTA)
as
all
of
these
compounds
are
recoverable
by
the
multiresidue
methods
of
PAM
I.
The
residues
of
concern
for
risk
assessment
for
primary
and
rotational
crops
are
PCNB
and
all
identified
metabolites
(
including
minor
metabolites).
The
MARC
further
recommends
that
the
review
team
determine
the
ratio
of
total
identified
residues
to
parent
plus
PCA
and
PCTA
and
apply
this
factor
to
the
residue
data
to
estimate
the
levels
for
risk
assessment.
The
team
should
determine
whether
there
are
adequate
metabolism
and/
or
confined
rotational
crop
data
to
determine
such
ratio.
If
adequate
data
are
not
available
for
this
task,
then
the
review
team
may
need
to
request
additional
metabolism
data.
This
may
be
the
case
for
cabbage­
like
crops
since
the
cabbage
metabolism
study
did
not
adequately
identify
the
metabolites.
A
rotational
crop
study
of
turnip
root
after
365
days
(
the
only
time­
interval
studied)
also
may
not
be
the
primary
substitute
for
metabolites
that
were
not
identified
in
cabbage
study
since
the
elapsed
time
between
application
and
planting
(
365
days)
is
Page
­
3­
too
long.
As
an
alternative,
the
Total
Radioactive
Residue
from
cabbage
metabolism
study
(
18
ppm)
can
be
used
as
the
total
concentration
of
residues
of
concern
in
cabbage­
like
crops
taking
into
account
the
similarity
of
use
pattern.
This
method
would
not
underestimate
the
residues.

Livestock
­
ruminants
and
poultry:
Studies
concerning
the
metabolism
of
PCNB
in
lactating
goats
and
poultry
were
submitted.
The
major
identified
metabolites
in
ruminant
tissues
included
PCA,
pentachlorothiophenol
(
PCTP),
tetrachlorothioanisole
(
TCTA),
N­(
pentachloroaniline)
glucuronide
(
PCA­
Gluc),
and
glucuronide
of
N­
hydroxypentachloroaniline
(
NOHPCA­
Gluc).
The
major
identified
metabolites
in
poultry
tissues
included
PCNB,
PCA,
pentachlorothiophenol
(
PCTA),
pentachlorothioanisole
sulfoxide
(
PCTA
sulfoxide),
TCA
sulfoxide,
tetrachlorophenyl
methyl
sulfone
(
TCP
methyl
sulfone)
and
tetrachloroaniline
methyl
sulfoxide
(
TCA
sulfoxide
isomers).
As
all
of
the
identified
metabolites
are
poly­
chlorinated
phenyl
compounds,
all
of
these
compounds
(
including
minor
metabolites)
are
of
concern.

The
residues
of
concern
for
tolerance
setting
purposes
in
livestock
are
PCNB,
PCA,
and
PCTA.
The
residues
of
concern
for
risk
assessment
for
livestock
are
PCNB
and
all
identified
metabolites.
The
MARC
further
recommends
that
the
review
team
determine
the
ratio
of
total
identified
residues
to
parent
plus
PCA
and
PCTA.
The
team
should
determine
whether
there
are
adequate
metabolism
data
to
determine
such
ratio.
If
adequate
data
are
not
available
for
this
task,
then
the
review
team
may
need
to
request
additional
metabolism
data.

Water:
Environmental
fate
data
suggest
that
PCNB
is
persistent
and
slightly
mobile
to
immobile
in
most
soils.
The
major
degradates
identified
in
the
fate
studies
are
PCA,
PCTA,
and
pentachlorobenzene
(
PCB),
but
only
PCA
was
present
at
>
10%
of
the
applied
radioactivity.
Pentachlorophenyl
(
PCP)
was
identified
under
anaerobic
conditions
in
one
of
the
studies.
PCP
is
a
B2
carcinogen
(
Q1
*
=
0.12
(
mg/
kg/
day)­
1
The
residues
of
concern
in
drinking
water
are
PCNB,
PCA,
and
PCP
as
PCA
was
the
only
identified
metabolite
which
comprised
>
10%
of
the
applied
radioactivity
and
PCP
is
of
known
toxicity.
If
the
review
team
are
unable
to
model
for
PCP
then
the
team
should
characterize
the
available
data
for
PCP
and
determine
the
level
at
which
it
is
of
concern
for
cancer.

Summary
of
MARC
Decision
As
all
the
metabolites
of
PCNB
are
poly­
chlorinated
phenyl
compounds
and
thus
of
toxicological
concern,
the
MARC
decision
was
that
PCNB
and
all
its
metabolites
(
including
minor
metabolites)
are
of
concern
in
plants
and
animal
commodities.
Because
of
lack
of
monitoring
data
as
well
as
field
trial
data
on
every
metabolite
of
PCNB
in
plants
and
animals,
MARC
members
suggested
using
metabolism
studies
in
plants
and
animals
to
derive
a
ratio
of
all
residues
of
concern
to
those
residues
in
tolerance
expression
(
PCNB,
PCA,
PCTA)
which
are
recovered
by
a
multi­
residue
method
and
using
that
ratio
to
estimate
the
concentration
of
residues
of
concern
from
field
trial
or
monitoring
data.
The
following
Table
summarizes
the
MARC
decisions
for
residues
of
concern
and
tolerance
expression
of
PCNB.
Page
­
4­
Chemical:
PCNB
(
pentachloronitrobenzene)

Date:
16­
April­
2003
Residues
of
Concern
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Plants
­
Primary
crops
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Plants
­
Rotational
crops
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Livestock
­
Ruminant
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Livestock­
Poultry
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Water
Parent,
PCA,
and
PCP
N/
A
PCA
=
pentachloraniline.
PCTA
=
pentachlorothioisole
or
methyl
pentachlorophenyl
sulfide.
PCP
=
pentachlorophenol
cc:
SF,
RF,
List
A
File,
Mohsen
Sahafeyan,
D.
Locke
(
RRB2)
RDI:
C.
Olinger:
5/
27/
03;
A.
Nielsen
5/
27/
03
7509C:
RRB2:
CM­
2:
Room
712D:
305­
6872:
PCNB
