1
Hexachlorobenze
Risk
Characterization
3/
4/
05
Introduction
Hexachlorobenzene
(
HCB)
is
a
recognized
contaminant
of
several
agricultural
pesticides,
as
well
as
the
wood
preservative
pesticide
pentachlorophenol.
Several
non­
pesticidal
sources
of
HCB
also
exist,
including
HCB
as
a
by­
product
or
waste
material
in
the
production
of
several
chlorinated
solvents
such
as
carbon
tetrachloride
and
trichloroethylene.

As
a
result
of
an
agreement
between
the
chemical
manufacturers
of
pentachlorophenol
and
the
EPA,
manufacturers
agreed
to
reduce
hexachlorobenzene
contamination
of
pentachlorophenol
to
no
more
than
75
parts
per
million.
Surveillance
monitoring
of
PCP
samples
have
detected
HCB
at
levels
generally
less
than
50
ppm
(
ATSDR,
2002).

The
Office
of
Pesticide
Programs
(
OPP)
has
published
RED
documents
for
both
Chlorothalonil
and
Dimethyl
tetrachloroerephthalate,
in
which
risks
associated
with
potential
exposure
to
HCB
were
assessed.
While
the
level
of
risk
for
dietary
and
drinking
water
exposure
to
HCB
contained
within
both
chlorothalonil
and
and
DCPA
was
below
the
Agency's
level
of
concern,
areas
of
concern
were
identified
for
both
occupational
and
residential
exposure
to
HCB.
In
response
to
these
concerns,
the
Agency
took
specific
measures
to
ensure
that
the
level
of
risk
would
be
made
acceptable,
either
through
the
requirement
of
use
of
protective
equipment
in
the
occupational
setting,
or
through
cancellation
of
residential
uses
for
these
two
pesticide
chemicals.
The
risk
assessment
for
HCB
in
PCP
will
focus
primarily
upon
the
use
of
PCP
as
a
wood
preservative
pesticide
and
the
potential
exposure
to
HCB
through
this
use.
This
risk
assessment
includes
only
occupational
and
residential
exposures,
as
there
are
no
dietary
or
drinking
water
concerns
for
PCP
as
a
wood
preservative
antimicrobial
pesticide.

The
OPP
has
not
requested
specific
toxicology
studies
on
hexachlorobenzene
as
this
chemical
is
not
under
the
regulatory
authority
of
OPP,
but
there
are
available
scientific
data
in
the
peer
reviewed
literature
which
appear
to
adequately
characterize
the
toxicity
of
hexachlorobenzene,
especially
a
recent
publication
by
the
Agency
for
Toxic
Substances
and
Disease
Registry
on
hexachlorobenzene
(
ATSDR,
2002).
In
addition,
the
USEPA
Office
of
Water
(
OW)
has
published
a
health
advisory
document
on
hexachlorobenzene
which
contains
numerous
references
to
the
scientific
literature
and
which
have
been
peer
reviewed
by
OW
prior
to
inclusion
in
the
Health
Advisory.
Thus,
hazard
characterization
will
rely
primarily
upon
previous
work
conducted
by
both
the
OPP's
Health
Effects
Division
as
well
as
work
by
ATSDR
and
OW.

Hazard
Characterization
The
toxicology
of
hexachlorobenzene
is
discussed
in
detail
within
the
1988
Drinking
Water
Criteria
Document
for
Hexachlorobenzene,
prepared
by
the
U.
S.
EPA's
Office
of
Health
and
Environmental
Assessment,
and
the
ATSDR
Toxicological
Profile
for
Hexachlorobenzene,
dated
February
2001
Both
assessments
characterize
the
acute
toxicity
of
HCB
as
low,
with
oral
LD50
values
in
the
range
of
3500­
10,000
mg/
kg
in
rats,
1700
mg/
kg
in
rats,
2600
mg/
kg
in
rabbits,
and
4000
mg/
kg
in
mice.

Short­
term
administration
of
hexachlorobenzene
to
rats
(
1000
mg/
kg/
day
for
7
days)
produced
liver
histopathology
and
altered
histochemistry
(
decreased
porphyrin
carboxylase
activity)
[
Kleiman
de
Pisarev
et
al.,
1990].
Other
liver
enzymes
(
delata­
aminolevulinate,
ornithine
decarboxylase)
have
also
been
shown
to
be
significantly
elevated
and/
or
decreased
at
similar
dose
levels
over
a
short
time
franme
(
3­
5
days)
[
Rajamanickam
and
Padmanaban,
1974].
Feeding
of
hexachlorobenzene
at
500
mg/
kg/
day
in
the
diet
for
5
days
produced
increased
liver
weight
as
well
as
increases
in
microsomal
protein,
RNA,
1
phospholipid
content
and
NADPH­
cytochrome
c
reductase
activity
[
Rajamanickam
and
Padmanaban,
1974].

Subchronic
administration
of
HCB
to
rats
at
doses
from
0.5
mg/
kg/
day
to
50
mg/
kg/
day
resulted
in
increased
liver
weight
and
increased
porphyrin
levels
in
liver,
kidney,
and
spleen.
Increased
mortality
as
well
as
neurologic
symptoms
(
tremors
and
ataxia)
was
observed
at
doses
of
32
mg/
kg/
day
and
above.
Female
rats
have
ben
shown
to
be
more
susceptible
to
the
toxic
effects
of
HCB
than
male
rats,
the
difference
being
related
to
the
faster
biotransformation
of
HCB
in
females
vs.
males.

Hexachlorobenzene
has
also
been
shown
to
produce
immunotoxic
effects
in
several
species
of
experimental
animals.
Administration
of
HCB
via
the
diet
at
0,
50,
or
150
mg/
kg/
day
to
pregnant
Wistar
rats
and
continuation
of
pups
on
HCB
diets
until
5
weeks
of
age
showed
increases
in
serum
IgM
and
IgG
concentrations.
Proliferation
of
high­
endothelial
venules
in
lymph
nodes
and
lymphoid
hyperplasia
of
the
splenic
white
pulp
was
observed
in
rats
given
HCB
at
25
and
100
mg/
kg/
day
for
3
weeks
[
Vos
et
al.,
1979].
Increased
levels
of
highly
carboxylated
porphyrins
in
the
spleen
of
female
Wistar
rats
administered
50
mg/
kg
HCB
and
increased
porphyrins
in
the
spleen
of
female
Charles
River
rats
administered
8
mg/
kg/
day
for
15
weeks
was
observed
[
Kuiper­
Goodman
et
al.,
1977;
Kennedy
and
Wigfield,
1990].
Decreased
resistance
to
infection
with
Listeria
monocytogenes
and
Trichinella
spiralis
was
also
noted
in
the
pregnant
rats
receiving
HCB.
Alterations
in
cellular
and
humoral
immunity
have
also
been
noted
(
Vos
et
al.,
1979a;
Lose
et
al.,
1978
a,
b).

Studies
of
HCB
reproductive
and
developmental
toxicity
demonstrate
that
HCB
crosses
the
placenta
and
is
present
in
milk
of
nursing
dams.
In
a
4­
generation
reproduction
toxicity
study
(
Grant
et
al.,
1977),
doses
of
16
and
32
mg/
kg
produced
increased
mortality
in
maternal
rats
prior
to
weaning,
reduced
fertility
index
and
decreased
average
litter
size.
All
pups
born
alive
at
these
2
dose
levels
died
within
5
days
of
birth.
The
NOAEL
in
this
study
was
reported
as
1
mg/
kg
HCB.
In
another
reproduction
study
(
Kitchin
et
al.,
1982),
female
Spreague­
Dawley
rats
were
fed
diets
containing
0,
3,
4,
5,
6
or
7
mg/
kg
HCB
and
mated
after
96
days
to
produce
the
first
litter,
and
then
bred
12
days
after
weaning
of
the
first
litter.
Increased
mortality
was
observed
in
both
litters
at
21­
days
post­
partum
at
all
dose
levels
for
both
generations.
Maternal
toxicity
was
observed
in
the
form
of
increased
numbers
of
intraalveolar
foamy
histiocytes
and
hypertrophy
and
proliferation
of
the
endothelial
cells
of
pulmonary
venules.
There
did
not
appear
to
be
a
NOAEL
established
in
this
study.
In
a
study
by
Mendoza
et
al.
(
1978),
a
significant
increase
in
liver
weight
was
observed
in
pups
nursed
by
dams
who
had
been
exposed
to
HCB
in
the
diet
at
4
mg/
kg
for
2
weeks.
This
effect
was
reversible
after
transfer
of
the
pups
to
control
nursing
dams.
Bailey
et
al.
(
1980)
examined
the
transfer
of
HCB
to
3
nursing
infant
Rhesus
monkeys
from
3
mothers
who
had
received
HCB
by
gavage
for
60
days
at
64
mg/
kg/
day.
Concentration
of
HCB
in
mothers'
milk
ranged
from
7.51­
186
ppm
during
dosing.
The
results
of
this
study
showed
blood
levels
of
HCB
in
the
infant
monkeys
(
0.42­
49.44ppm)
that
exceeded
those
of
the
mothers
(
0.41­
16.16ppm),
and
clinical
signs
of
toxicity
in
infants
while
mothers
were
asymptomatic.
In
contrast
to
these
results,
there
were
no
apparent
effects
of
HCB
on
fetal
development
when
HCB
was
administered
to
either
pregnant
rats
at
5,
10,
20,
40,
or
80
mg/
kg
on
gestation
days
6­
16
or
to
rabbits
at
0.1,
1.0,
or
10
mg/
kg
on
days
1­
27
of
gestation.
In
a
study
designed
to
examine
the
contribution
of
hexachlorobenzene
to
fetal
malformations
observed
2
from
administration
of
pentachlorobenzene,
100
mg/
kg/
day
was
administered
by
gavage
to
10
pregnant
CD­
1
mice
(
Courtney
et
al.,
1976).
The
abnormalities
observed
in
fetuses
from
this
study
(
cleft
palate,
small
kidneys,
enlarged
renal
pelvis)
were
concluded
to
be
the
result
of
HCB
exposure.

More
recent
investigations
into
the
developmental
and
reproductive
effects
of
HCB
reveal
effects
at
the
cellular
level
at
lower
doses
of
HCB
than
previously
reported.
For
example,
in
a
study
by
Bourque
et
al.
(
1995),
twenty
6­
13
year
old
female
monkeys
were
randomly
assigned
to
one
of
5
treatment
groups
and
received
0,
0.01,
0.1,
1.0,
or
10.0
mg/
kg
HCB
administered
by
gelatin
capsule
for
13
weeks
to
examine
changes
in
ovarian
ultrastructural
histology.
The
results
of
this
study
demonstrated
that
HCB
in
doses
as
low
as
0.01
mg/
kg
caused
histological
changes
to
primary
ovarian
follicles
in
monkeys.
In
a
second
study
by
Jarrell
et
al.
(
1993),
sixteen
sexually
mature
female
cynomolgus
monkeys
(
4/
group)
were
administered
gelatin
capsules
orally
once/
day
in
doses
of
either
0.0,
0.1,
1.0,
or
10.0
mg
hexachlorobenzene
(
HCB)/
kg/
day
for
90
days.
The
results
of
examination
of
ovaries
showed
a
decline
in
the
total
number
of
oocytes
and
primordial
follicles
but
no
change
in
the
number
of
antral
and
preantral
follicles
and
corpea
lutea.
At
increased
dose
levels
the
nuclear
and
nucleolar
membranes
became
less
distinct
and
oocyte
nuclei
became
increasingly
dense,
granular,
and
misshapen.
Vacuole
cytoplamic
increase
and
aggregated
lysosomes
were
observed.
All
the
above
histological
observations
were
perceptible
in
lose
dose
animals
(
0.1
mg/
kg/
day)
but
increased
in
severity
in
a
dose­
dependant
fashion.

Significant
neurotoxicity
has
also
been
observed
in
animal
studies
with
hexachlorobenzene,
and
neurotoxicity
has
been
reported
in
adult
animals
without
evidence
of
porphyrin
accumulation
or
histological
alterations.
Electrophysiological
alterations
were
observed
in
dogs
which
received
HCB
at
approximately
50
mg/
kg/
day
for
21
days
[
Sundlof
et
al.,
1981].
Reduced
nerve
conduction
in
the
sciatic
nerve
as
well
as
fibrillations
and
repetitive
or
pseudomyotonic
discharges
were
observed
in
rats
administered
40
mg/
kg/
day
HCB
for
20
weeks
[
Sufit
et
al.,
1986].

In
a
study
by
Lilienthal
et
al.
(
1996),
52
female
Wistar
rats
were
divided
into
4
groups
and
administered
diets
containing
0,
4,
8,
or
16
mg/
kg
hexachlorobenzene
(
HCB)
for
90
days.
Following
the
90
days'
treatment,
10
females
per
dose
level
were
mated
to
untreated
males,
and
exposure
of
mated
females
continued
until
PND
21
at
which
time
the
mothers
were
sacrificed.
The
offspring
were
then
continued
on
the
same
dose
levels
as
maternal
rats
until
PND
150,
at
which
time
all
rats
were
given
control
diet.
Testing
of
male
offspring
was
conducted
on
PN
days
21
(
open
field
testing),
PN
90
(
active
avoidance
learning),
and
PN
150
(
operant
conditioning).
The
results
of
behavioral
testing
showed
no
effect
of
HCB
exposure
on
open
field
activity
in
pups
at
any
dose,
but
a
dose­
related
decrease
in
the
post­
reinforcement
pause
was
observed
on
PN
day
150,
and
was
statistically
significant
at
both
the
8
and
16
mg/
kg
dose
levels.
The
results
of
these
studies
suggest
that
HCB
induces
increases
in
activity
levels
and/
or
affects
learned
responses
in
early
post­
natal
development
in
the
absence
of
any
overt
signs
of
toxicity
in
maternal
animals.
In
a
study
by
Goldey
and
Taylor
(
1992),
3
groups
of
10
virgin
female
rats
were
administered
HCB
in
corn
oil
by
oral
gavage
at
0.0,
2.5,
or
25.0
mg/
kg
body
weight
Two
weeks
following
dosing,
treated
females
were
mated
with
non­
treated
males
and,
at
birth
the
litters
were
culled
to
8
pups
(
4
males
and
4
females
when
possible).
Pups
were
weighed
at
PND
1,3,6,9,12,14,
and
28
and
weaned
at
PND
21.
The
following
variables
were
studied
in
all
pups:
negative
geotaxis
reflex
at
PND
6,
8,
and
10,
olfactory
3
homing
at
PND
9,
10,
and
11,
and
motor
activity
via
home
cage
locomotor
movement
from
PND
15­
20.
The
acoustic
startle
reflex
was
measured
in
2
male
and
2
female
pups
per
litter
at
PND
23
and
again
in
the
same
pups
at
PND
90.
Visual
discrimination
learning
was
assessed
on
PND
40.
Motor
activity
of
mature
offspring
was
assessed
at
PND
60.
Litters
exposed
maternally
to
HCB
had
significantly
increased
exploratory
activity
in
home
cage
motor
assessment
when
compared
to
control
animals
at
PND
19
and
20.
Acoustic
startle
reflex
was
significantly
reduced
in
the
higher
HCB
group
than
in
the
lower
HCB
and
control
groups.
When
acoustic
startle
reflex
was
reassessed
at
PND
90,
males
maternally
exposed
to
100
mg/
kg
had
an
elevated
response
when
compared
to
the
10
mg/
kg
group
and
the
control
group;
the
10
mg/
kg
group
also
exhibited
a
significantly
elevated
response
when
compared
to
the
control
group.
In
females,
only
those
maternally
exposed
to
100
mg/
kg
exhibited
a
significantly
higher
response
rate.
Maternal
exposure
to
HCB
had
no
effect
on
PND
60
motor
activity
or
visual
discrimination.
Tissue
concentrations
of
HCB
in
rat
pups
were
observed
to
peak
around
PND
4,
with
a
decline
observed
thereafter
to
levels
approximately
50%
of
peak
values
by
PND
14.
The
results
of
this
study
indicates
that
maternal
exposure
to
HCB
induces
hyperactivity
in
post­
natal
rats
in
the
absence
of
any
other
overt
signs
of
toxicity
in
maternal
animals.

Mutagenicity
data
on
HCB
do
not
show
a
direct
interaction
with
DNA.
HCB
was
found
to
be
negative
for
reverse
mutation
activity
in
Salmonella
typhimurium
strains
TA100
and
TA98
[
Siekel
et
al.,
1991],
and
was
also
negative
in
a
DNA
repair
assay
using
E.
coli
[
Siekel
et
al.,
1991].
Despite
the
lack
of
direct
genotoxic
activity
of
HCB,
this
chemical
has
been
shown
to
produce
increased
incidence
of
hepatomas,
hemangioendotheliomas,
and
thyroid
tumors
in
mice,
hamsters,
and
rats
(
Smith
and
Cabral,
1980;
Cabral
et
al.,
1979).

Dose­
Response
Assessment
Existing
toxicology
end
points
for
characterization
of
risk
from
exposure
to
HCB
consist
of
a
chronic
Reference
Dose
value
of
0.0008
mg/
kg/
day
and
a
published
Q1*
of
1.7
(
USEPA,
1991).
The
Agency
has
classified
HCB
as
a
B2
(
probable
human)
carcinogen,
based
on
induction
of
tumors
of
the
thyroid,
liver,
and
kidney
in
three
rodent
species
(
USEPA
IRIS,
1996).
The
published
Q1*
value
of
1.7
was
originally
calculated
using
a
2/
3
animal
to
human
scaling
factor,
and
the
Agency
has
recently
switched
to
use
of
a
3/
4
animal­
to­
human
scaling
factor.
Therefore,
the
existing
value
of
1.7
is
adjusted
using
the
3/
4
scaling
factor
to
give
a
value
of
1.02
(
mg/
kg/
day)­
1.
(
HED
memorandum
from
William
Burnam
dated
June
21,
1995)
For
purposes
of
risk
characterization
from
exposure
to
treated
wood,
non­
cancer
endpoints
are
needed
in
order
to
characterize
risk
from
dermal,
incidental
oral,
and
inhalation
exposures
to
HCB,
similar
to
what
has
been
done
for
pentachlorophenol.
The
Antimicrobials
Division,
Office
of
Pesticide
Programs,
has
selected
toxicity
endpoints
for
HCB
for
use
in
exposure
and
risk
assessments.
These
endpoints
were
selected
using
the
available
scientific
literature
on
HCB.
A
summary
of
these
endpoints
is
shown
in
the
following
table.
4
Toxicity
Endpoints
for
Hexachlorobenzene
Endpoint
Dose/
UF
Effect
identified
Study
Selected
Incidental
Oral,
Short­
Term
NOAEL
=
40
mg/
kg/
day
body
weight
loss,
hyperesthesia,
tremors,
convulsions
in
maternal
rats
at
60
mg/
kg/
day.
Developmental
toxicity
­
rat
(
Khera,
1974)

Incidental
Oral,
Intermediate­
term
NOAEL
=
0.5
mg/
kg/
day
increased
incidence
of
liver
porphyrin
levels
in
female
rats
at
2
mg/
kg/
day
15
Week
Oral
Toxicity
­
Rat
(
Kuiper­
Goodman
et
al,
1977)

Short­
Term
(
Dermal)
NOEL=
40
mg/
kg/
day
body
weight
loss,
hyperesthesia,
tremors,
convulsions
in
maternal
rats
at
60
mg/
kg/
day.
Developmental
Toxicity
­
Rat
(
Khera,
1974)

Intermediate­
Term
(
Dermal)
NOEL=
0.5
mg/
kg/
day
increased
incidence
of
liver
porphyrin
levels
in
female
rats
at
2
mg/
kg/
day
15
Week
Oral
Toxicity
­
Rat
(
Kuiper­
Goodman
et
al,
1977)

Long­
Term
(
Dermal)
NOAEL
=
0.08
mg/
kg/
day
hepatic
centrilobular
basophilic
chromogenesis
at
0.29
mg/
kg/
day
Chronic
Toxicity­
Rat
(
Arnold
et
al.,
1985)

Inhalation
No
route­
specific
inhalation
data
were
available
for
hexachloropbenzene.
Therefore,
in
accordance
with
Agency
policy,
oral
endpoints
and
route
extrapolation
were
performed
to
assess
inhalation
risks
as
needed.

Oral
Cancer
Slope
Factor
Q*=
1.02
(
mg/
kg/
day)­
1
(
Extrapolated
using
a
Q*
of
1.7
mg/
kg/
day
derived
from
a
linearized
multistage
model
to
which
a
3/
4
scaling
factor
was
applied:
1.7
x
0.6
=
1.02)
B2
(
probable
human
carcinogen)
based
on
data
showing
significant
increases
in
liver
and
renal
tumor
incidences
in
hamsters
and
rats
Sourced
to
EPA
REDs
for
DCPA,
November
1998,
and
Chlorothalonil,
April
1999
and
EPA's
IRIS
Database.
The
Agency
typically
will
not
allow
non­
dietary
risks
to
exceed
10
­
4.

Since
oral
endpoints
were
selected
for
HCB
risk
assessments,
and
the
occupational
exposures
are
attributed
primarily
to
the
dermal
route,
a
dermal
absorption
value
of
26.0
%
was
recommended
for
use
in
route­
to­
route
extrapolations.
Note
that
derived
HCB
doses
used
in
the
assessment
are
conservatively
assumed
to
represent
dermal
exposure.
A
back
calculation
was
performed
to
convert
absorbed
doses
of
PCP
into
equivalent
HCB
dermal
doses:
Absorbed
short­,
intermediate­,
and
long­
term
PCP
doses
were
multiplied
by
the
ratio
of
HCB
per
batch
of
PCP
(
75
ppm)
then
adjusted
by
multiplying
by
the
difference
in
dermal
absorption
between
PCP
(
i.
e.,
40%)(
U.
S.
EPA,
1997a)
and
HCB
(
i.
e.,
26%)
(
i.
e.,
.26/.
40
=.
65).
5
Exposure
Assessment
The
occupational
exposure
assessment
for
HCB
as
a
contaminant
in
pentachlorophenol­
treated
wood
has
been
assessed
in
detail
in
the
companion
human
exposure
chapter
by
Doreen
Aviado.
Tables
3
and
5
of
the
exposure
chapter
present
details
of
the
exposure
doses
and
risks.
Here,
summary
information
is
provided.

Occupational
Handler
Margins
of
Exposure
and
Risk
Handler
exposure
to
PCP
wood
preservatives,
as
product
concentrates
and
treatment
solutions,
results
in
potential
exposure
to
the
HCB
microcontaminant
during
handler
operations
in
pressure
treatment
plants.
The
following
handler
scenarios
for
pressure
treatment
uses
have
been
identified
from
the
PCP
biomonitoring
and
inhalation
study
entitled
Inhalation
Dosimetry
and
Biomonitoring
Assessment
of
Worker
Exposure
to
Pentachlorophenol
During
Pressure­
Treatment
of
Lumber
(
PTF,
1999)
further
detailed
in
the
PCP
RED
Human
Exposure
Chapter:

(
1a)
Applying
crystalline
technical
grade
product­
Pressure
Treatment
Operator;
(
1b)
Applying
liquid
formulation­
Pressure
Treatment
Operator;
(
2a)
Applying
crystalline
technical
grade
product­
Pressure
Treatment
Assistant;
and
(
2b)
Applying
liquid
formulation­
Pressure
Treatment
Assistant
Derived
HCB
doses
used
in
the
assessment
were
assumed
to
represent
dermal
exposure.
Thus,
a
back
calculation
was
performed
to
convert
absorbed
doses
of
PCP
from
the
biomonitoring
study
into
equivalent
HCB
dermal
doses.
Absorbed
short­,
intermediate­,
and
long­
term
PCP
doses
were
multiplied
by
the
ratio
of
HCB
per
batch
of
PCP
(
75
ppm)
then
adjusted
by
multiplying
by
the
difference
in
dermal
absorption
between
PCP
(
i.
e.,
40%)
and
HCB
(
i.
e.,
26%)
(
i.
e.,
.26/.
40
=.
65).

As
shown
in
the
exposure
assessment,
there
were
no
identified
non­
cancer
risks
of
concern
for
short­,
intermediate­,
or
long­
term
occupational
exposures
to
HCB,
i.
e.
calculated
MOEs
were
>
100.
There
were
also
no
identified
cancer
risks
of
concern
for
occupational
handlers
(
risks
were
in
the
range
of
E­
7
to
E­
8).

Occupational
Postapplication
Margins
of
Exposure
and
Risk
In
the
pressure
treatment
industry,
postapplication
exposure
may
result
from
typical
work
tasks
associated
with
removing
wet
treated
wood
from
treatment
cylinders,
reentry
activities
in
treatment
areas
including
maintenance
of
treatment
equipment
and
cleanup,
handling
freshly­
treated
wood
to
bore
test
core
samples,
stacking/
loading
wet
wood
onto
drip
pads,
and
handling
dry
wood
for
storage
or
transport.
The
following
postapplication
exposure
scenarios
for
pressure
treatment
uses
have
been
identified
from
the
PCP
biomonitoring
and
inhalation
study
entitled
Inhalation
Dosimetry
and
Biomonitoring
Assessment
of
Worker
Exposure
to
Pentachlorophenol
During
Pressure­
Treatment
of
Lumber
(
PTF,
1999)
further
detailed
in
the
PCP
RED
Human
Exposure
Chapter:
6
(
1)
Pressure
Treatment
Loader
Operator;
(
2)
Pressure
Treatment
Test
Borer;
and,
(
3)
Pressure
Treatment
General
Helpers.

In
addition,
potential
occupational
postapplication
exposures
exist
for
electrical
utility
linemen
in
dermal
contact
with
PCP­
treated
utility
poles
during
installation
and/
or
while
working
on
in­
service
poles
The
Agency
has
determined
that
Margins
of
Exposure
(
MOEs)
of
100
or
greater
are
acceptable
for
assessment
of
non­
cancer
risk
from
short­,
intermediate­
and
long­
term
exposure
to
HCB.
MOEs
for
all
scenarios
evaluated
showed
no
risks
of
concern
for
any
of
the
occupational
postapplication
scenarios
assessed
(
i.
e.
calculated
MOEs
were
all
in
excess
of
100).
In
addition,
for
carcinogenic
risk,
none
of
the
occupational
postapplication
scenarios
assessed
exceeded
the
Agency's
level
of
concern
(
i.
e.,
E­
4)
for
cancer
aggregate
risks
and
were
within
the
E­
8
range.

Residential
Margins
of
Exposure
and
Risk
Residential
postapplication
exposure
to
the
HCB
microcontaminant
is
unlikely
to
occur
to
adult
and
child
populations
as
a
result
of
contact
with
PCP­
treated
wood
products
or
through
child
contact
with
PCP­
contaminated
soil
via
the
dermal
and
oral
route
(
i.
e.,
incidental
ingestion
of
HCB
microcontaminant
residues
through
hand­
to­
mouth
contact
and
direct
soil
ingestion).
The
Agency
has
not
conducted
an
exposure
and
risk
assessment
for
residential
populations
due
to
the
following
consideration:

°
The
opportunity
for
residential
consumer
contact
is
limited
since
PCP­
treated
wood
is
not
sold
to
the
general
public.
Rather
it
is
predominantly
marketed
for
commercial
installations
as
utility
poles.
Where
utility
poles
are
installed
on
home/
school
or
other
residential
sites,
child
contact
via
the
dermal
or
oral
routes
is
not
anticipated
since
play
activities
with
or
around
these
pole
structures
would
not
normally
occur
and
any
incidental
exposure
would
therefore
be
negligible.

Risk
Characterization
In
two
previous
RED
documents
issued
by
the
EPA,
risks
from
exposure
to
HCB
in
the
agricultural
pesticides
chlorothalonil
and
DCPA
were
assessed.
In
the
DCPA
RED
document,
chronic
dietary
and
chronic
drinking
water
risk
from
HCB
exposure
were
assessed,
as
well
as
carcinogenic
risk
from
occupational
and
residential
exposures.
As
an
impurity
in
DCPA,
the
worst
case
chronic
dietary
risk
showed
between
3­
5%
of
the
Reference
Dose
for
HCB
occupied
by
dietary
sources
of
exposure.
Carcinogenic
dietary
risk
from
HCB
exposure
was
calculated
as
7
x
10­
7,
using
a
Q*
of
1.02
mg/
kg/
day­
1.
Occupational
carcinogenic
risk
for
commercial
mixer/
loaders
using
a
wettable
powder
formulation
of
DCPA
was
calculated
as
1.9
x
10­
4
for
HCB.

For
chlorothalonil,
chronic
dietary
and
drinking
water
non­
cancer
risks
were
calculated
for
exposure
to
HCB
present
in
chlorothalonil.
Also,
carcinogenic
drinking
water
risk
was
also
calculated.
Aggregate
risks
for
HCB
were
included
for
chronic
non
­
cancer
risk
as
well
as
chronic
cancer
risk.
For
HCB
in
chlorothalonil,
chronic
dietary
risk
was
calculated
to
occupy
0.05%
of
the
RfD
for
HCB
in
the
highest
exposed
population
(
children
ages
1­
6).
Chronic
carcinogenic
risk
was
calculated
as
2.4
x
10­
7
for
the
U.
S.
population.
Chronic
non
­
cancer
risk
for
HCB
in
drinking
water
was
shown
to
occupy
less
than
1%
of
the
RfD
for
HCB,
while
aggregate
chronic
no
­
cancer
risk
was
also
shown
to
occupy
less
than
1%
of
the
RfD
for
HCB.
Aggregate
cancer
risk
for
HCB
in
chlorothalonil
was
calculated
as
2.4
x
10­
7
7
mg/
kg/
day­
1.
Occupational
cancer
risk
from
HCB
exposure
was
calculated
as
2.8
x
10­
5,
which
is
below
the
Agency's
level
of
concern.

Dietary
Risk
Use
of
pentachlorophenol
as
a
wood
preservative
is
restricted
to
non­
food
uses.
Therefore,
from
use
of
pentachlorophenol
as
a
wood
preservative,
it
is
not
expected
that
HCB
will
contribute
to
dietary
risk.

Drinking
Water
Risk
Behavior
of
HCB
in
surface
and
ground
water
is
expected
to
be
the
same
as
that
previously
described
in
the
chlorothalonil
RED,
i.
e.
contamination
of
groundwater
is
unlikely
due
to
the
high
binding
potential
of
HCB
to
soil
and
sediment.
This
can
also
be
expected
from
wood
preservative
use
of
PCP
where
the
treated
wood
may
come
into
contact
with
soil.
Therefore,
as
for
PCP,
there
is
not
expected
to
be
any
significant
contribution
to
drinking
water
risk
from
HCB
present
in
PCP,
as
it
has
not
been
previously
been
of
concern
from
HCB
present
in
the
food­
use
pesticides
chlorothalonil
and
DCPA,
and
the
incremental
contribution
to
the
environment
of
HCB
present
in
PCP­
treated
lumber
is
not
expected
to
add
to
the
risk
already
calculated
for
HCB.

Short­,
Intermediate­,
and
Chronic
Aggregate
Risk
Similar
to
that
of
pentachlorophenol,
as
there
is
no
significant
contribution
through
the
diet
or
drinking
water
from
the
wood
preservative
use,
an
aggregate
assessment
is
not
necessary
for
HCB.

Cumulative
Risk
Section
408
of
the
FFDCA
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
nonoccupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
Hexachlorobenzene
is
a
known
porphyrinogenic
agent,
which
is
characterized
by
increased
activity
of
ALA­
synthase
and
decreased
activity
of
uroporphyrinogen
decarboxylase
(
ATSDR,
2002).
The
exact
mechanism
of
porphyria
induction
is
not
known
with
certainty,
although
some
data
suggest
that
the
severity
of
induced
porphyria
is
increased
by
co­
administration
of
HCB
with
the
major
metabolites
pentachlorophenol
and
tetrachlorohydroquinone
(
ATSDR,
2002).
With
regard
to
carcinogenicity,
it
has
been
suggested
that
accumulation
of
iron
in
the
liver
may
potentiate
development
of
hepatic
tumors
by
HCB
(
ATSDR,
2002).
Further
research
is
needed
to
determine
whether
hexachlorbenzene
has
a
common
mechanism
of
toxicity
with
other
substances.
8
Endocrine
Disruption
The
Food
Quality
Protection
Act
(
FQPA;
1996)
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticides
and
inerts)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect...."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

Hexachlorobenzene
is
known
to
cause
multiple
adverse
effects
on
the
endocrine
system
(
ATSDR,
2002).
These
changes
include
decreased
serum
thyroxine,
increased
serum
parathyroid
hormone,
decreased
release
of
corticosterone
from
the
adrenal
gland,
and
changes
in
estradiol/
progesterone
levels
in
females.
Effects
on
ovarian
and
adrenal
hormones
have
been
hypothesized
to
reflect
alterations
in
steroidogenesis
in
these
tissues,
possibly
as
a
result
of
lipid
peroxidation
of
mitochondrial
membranes
(
ATSDR,
2002).
9
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