Document ID: EPA-HQ-OPP-2004-0402-0032
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-03-18T05:00Z

Page
1
of
22
TOXICOLOGY
AND
HUMAN
RISK
CHARACTERIZATION
An
Evaluation
of
Hazards
and
Risks
from
Exposure
to
Dioxin/
Furan
Contaminants
in
Pentachlorophenol­
treated
Wood
The
United
States
Environmental
Protection
Agency
(
U.
S.
EPA)

Office
of
Prevention,
Pesticides
and
Toxic
Substances
Office
of
Pesticide
Programs
Antimicrobials
Division
Risk
Assessment
and
Science
Support
Branch
3/
4/
05
Page
2
of
22
TABLE
OF
CONTENTS
1.0
BACKGROUND......................................................................................................................
3
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION....................................
3
2.1
Potential
Sources
of
CDD/
CDFs.................................................................................
4
2.2
Physical
Property
of
CDD/
CDFs
.................................................................................
4
3.0
HAZARD
CHARACTERIZATION......................................................................................
5
3.1
Non­
Carcinogenic
Effects............................................................................................
6
3.2
Mutagenicity
and
Carcinogenicity
..............................................................................
8
3.3
Toxic
Equivalency
Factors
(
TEFs)
and
Toxic
Equivalency
Quotient
(
TEQ)
.......
10
3.4
FQPA
Considerations................................................................................................
11
4.0
EXPOSURE
ASSESSMENT
.................................................................................................
14
4.1
Identification
of
Potential
Receptor
Populations.....................................................
14
4.1.1
Occupational
Handlers
...................................................................................
14
Primary
Occupational
Handlers.......................................................
14
Occupational
Postapplication
Exposure..........................................
15
4.1.2
Residential
Receptors
.....................................................................................
16
5.0
RISK
CHARACTERIZATION
............................................................................................
17
6.0
UNCERTAINTY
ANALYSIS...............................................................................................
17
7.0
REFERENCES .................................................................................................................
20
Page
3
of
22
1.0
BACKGROUND
The
purpose
of
the
risk
characterization
is
to
quantify
the
potential
health
risks
to
the
potential
receptors
associated
with
exposure
to
the
chemicals
of
concern.
As
part
of
the
pentachlorophenol
(
PCP)
Reregistration
Eligibility
Decision
(
RED)
Document
prepared
by
the
US
EPA,
presented
herein
is
the
risk
characterization
risk
characterization
of
Occupational
and
Residential
Exposure
to
the
Dioxin/
Furan
microcontaminants
(
CDDs/
CDFs)
contained
in
Pentachlorophenol
(
PCP).

2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
Polychlorinated
dibenzo­
p­
dioxins
(
CDDs)
and
polychlorinated
dibenzofurans
(
CDFs)
are
members
of
a
family
of
polychlorinated
isomers
of
"
dioxin­
like"
compounds.
CDD
congeners
may
contain
from
1
to
8
chlorine
atoms
at
various
sites
on
the
aromatic
rings
of
the
molecule.
Physical
and
chemical
properties
and
toxicity
vary
with
the
degree
of
chlorination.
The
most
toxic
congener
of
the
family
is
2,3,7,8­
tetrachlorodibenzo­

pdioxin
(
2,3,7,8­
TCDD).
The
toxicity
of
other
CDD/
CDF
isomers
as
well
as
coplanar
polychlorinated
biphenyls
(
PCBs)
have
been
characterized
in
relation
to
2,3,7,8­
TCDD
(
WHO,

1998).

The
U.
S.
EPA
Office
of
Research
and
Development,
beginning
in
1991,
undertook
a
comprehensive
scientific
assessment
of
the
health
risks
from
exposure
to
2,3,7,8
TCDD
and
chemically
similar
compounds
in
collaboration
with
scientists
from
inside
and
outside
the
Federal
government.
The
most
recent
draft
of
this
document
is
posted
at
http://
cfpub.
epa.
gov/
ncea/
cfm/
recordisplay.
cfm?
deid=
55264.
It
should
be
noted
that
this
document
is
a
draft
for
review
purposes
only
and
does
not
constitute
U.
S.
Environmental
Protection
Agency
policy.
While
this
draft
assessment
contains
a
comprehensive
review
of
the
hazards
and
exposures
associated
with
dioxin
and
dioxin­
like
family
of
compounds
from
all
sources
of
exposure,
the
present
assessment
from
the
Antimicrobials
Division
covers
only
those
exposures
and
risks
associated
with
exposure
to
the
dioxin
and
furan
contaminants
of
pentachlorophenol
as
a
wood
preservative
chemical.
Page
4
of
22
2.1
Potential
Sources
of
CDDs/
CDFs
CDDs/
CDFs
are
not
intentionally
manufactured
but
are
formed
as
impurities
from
a
variety
of
processes.
Sources
include
combustion
(
including
waste
incineration,
burning
of
various
fuels,

forest
fires,
and
open
burning
of
wastes),
chemical
manufacturing
(
as
by­
products
from
manufacture
of
chlorine
bleached
wood
pulp,
chlorinated
phenols,
and
phenoxy
herbicides),

biochemical
and
photochemical
processes
(
composting),
and
reservoir
sources
(
such
as
soils,

sediment,
and
water
,
where
previously
formed
CDDs/
CDFs
or
dioxin­
like
PCBs
have
the
potential
for
redistribution
and
circulation
into
the
environment).
Environmental
release
of
CDDs/
CDFs
occur
from
all
of
these
sources,
but
of
all
sources,
air
release
from
combustion
is
the
dominant
source.
It
has
been
stated
that
quantifiable
emissions
of
dioxins
from
combustion
sources
are
more
than
an
order
of
magnitude
greater
than
quantifiable
emissions
from
all
other
categories
combined
(
USEPA,
2000).
(
ATSDR
1989;
NATO
1988a
and
1988b;
USEPA
1980).

Air
emissions
of
CDDs/
CDFs
from
combustion
processes
may
result
in
transport
of
these
compounds
over
long
distances
before
deposition
on
land
or
in
water.
During
transport,
the
compounds
are
either
adsorbed
to
particulate
matter
or
present
in
the
vapor
phase
and
can,
during
the
course
of
time,
undergo
association
with
aerosols
as
they
are
transported
(
Broman
et
al.

1991).
In
the
case
of
the
accidental
release
of
TCDD
at
Seveso,
Italy,
it
has
been
estimated
that
dispersion
of
this
compound
from
air
to
soil
followed
an
exponential
decay
pattern
along
the
downwind
direction.

2.2
Physical
Property
of
CDDs/
CDFs
CDDs/
CDFs
are
generally
expected
to
be
relatively
immobile
in
the
soil/
groundwater
system
due
to
strong
sorption
properties;
surface­
applied
contamination
is
expected
to
be
confined
to
the
uppermost
6­
12
inches
of
soil.
However,
releases
of
CDD
and
CDF
contaminants
from
soil
via
erosion
and
runoff
may
be
significant
(
USEPA,
2000).
Vapor
phase
diffusion
and
subsequent
volatilization
from
surface
soils
may
be
significant
in
the
absence
of
other
transport
processes;

translocation
of
adsorbed
CDDs/
CDFs
with
soil
particles
may
also
be
important.
In
general,

persistence
studies
indicate
that
levels
of
CDDs/
CDFs
in
soil
diminish
sharply
within
the
first
6­
15
months,
followed
by
negligible
changes;
the
initial
decrease
is
attributed
to
photodecomposition
and
heat­
promoted
volatilization
at
the
surface.
Several
studies
have
reported
that
photolysis
is
the
major
route
of
TCDD
disappearance.
In
laboratory
experiments,
photodegradation
of
polychlorinated
dibenzo­
p­
dioxins
occurred
by
preferential
dechlorination
at
the
2,3,7,8­
positions;
Page
5
of
22
continued
irradiation
resulted
in
some
decomposition
of
the
dibenzo­
p­
dioxin
structure.

Polychlorinated
dibenzo­
p­
dioxins
exhibit
relatively
strong
resistance
to
microbial
degradation
in
soils.
The
primary
pathway
of
concern
in
soil/
groundwater
systems
is
the
migration
to
groundwater
drinking
water
supplies
via
colloidal
transport.
In
surface
waters,
CDD/
CDFs
are
expected
to
remain
strongly
adsorbed
and
persist
in
the
suspended
sediment
or
bottom
sediment.

The
entrance
of
dioxins
into
water
via
erosion
and/
or
runoff
of
contaminated
soil
leads
to
bioaccumulation
in
fish
through
contact
with
water,
sediment,
and
ingestion
of
aquatic
organisms.

3.0
HAZARD
CHARACTERIZATION
In
mammals,
CDD/
CDFs
are
readily
absorbed
through
the
gastrointestinal
tract.
Absorption
through
intact
skin
has
also
been
reported
but
is
considered
limited.
Absorption
may
decrease
dramatically
if
CDD/
CDFs
are
adsorbed
to
particulate
matter
such
as
activated
carbon
or
soil.

After
absorption,
CDD/
CDFs
are
distributed
to
tissues
high
in
lipid
content
and
to
liver
where
they
are
slowly
metabolized
by
the
cytochrome
P­
450
monooxygenase
system.
The
high
lipophilicity
of
the
CDDs/
CDFs
can
result
in
significant
half­
lives
of
elimination.
Metabolites
of
CDDs/
CDFs
may
be
excreted
in
the
urine
and
feces.
Unmetabolized
CDDs/
CDFs
can
be
eliminated
in
the
feces
and
in
milk.
There
is
ample
experimental
evidence
that
the
toxic
response
to
the
CDDs/
CDFs
is
mediated
through
cytosolic
Ah­
receptor
site
binding.
Differences
in
the
magnitude
of
the
toxic
response
may
be
related
to
the
affinity
of
binding
and/
or
magnitude
of
the
biochemical
response
following
binding
(
USEPA
1986).

The
primary
routes
of
human
dietary
exposure
to
CDDs/
CDFs
have
been
determined
to
be
through
ingestion
of
animal
products
which
have
ingested
plant
material
concentrated
with
dioxins
through
atmospheric
deposition
to
soil,
and
through
ingestion
of
aquatic
organisms
that
have
bioaccumulated
dioxins
through
runoff
from
soil
in
to
water.
Elevated
levels
of
dioxin
have
also
been
observed
in
cattle
that
have
come
into
contact
with
pentachlorophenol­
treated
wood
(
USEPA,
2000).
As
a
result
of
such
exposures,
the
average
tissue
level
of
CDD/
CDF/
PCBs
in
the
adult
human
population
has
been
estimated
at
25
parts
per
trillion
lipid
(
USEPA,
2000).

If
2,3,7,8­
TCDD
is
ingested
in
drinking
water,
fatty
or
oily
foods,
other
foods,
paper,
dust,

sludge,
or
soil,
>
50%
of
the
oral
dose
is
expected
to
be
bioavailable.
It
may
be
assumed
that,
due
to
their
high
lipophilicity,
there
would
be
100%
absorption
of
TCDD
or
TCDF
vapors
entering
Page
6
of
22
the
respiratory
tract.
Following
dermal
exposure
to
2,3,7,8­
TCDD
in
soil,
approximately
1%
of
the
TCDD
was
found
in
the
liver.
When
TCDDs
or
TCDFs
were
applied
to
the
skin
in
an
organic
solvent
(
acetone),
up
to
40%
of
the
TCDDs
and
48%
of
the
TCDFs
were
absorbed
by
72
hours
(
USEPA
1990).
In
contrast,
uptake
of
2,3,7,8­
TCDD
by
crops
from
soils
is
not
significant
(
IRP
1989;
USEPA
1990).

3.1
Non­
Carcinogenic
Effects
The
major
toxic
effects
produced
by
CDDs/
CDFs
include
lethality,
chloracne,
liver
damage,

cancer,
immunosuppression
(
including
thymic
involution),
developmental
toxicity,
endocrine
disruption,
and
reproductive
toxicity.
Chloracne
is
usually
only
observed
after
substantial
exposure
to
2,3,7,8
TCDD
(
USEPA,
2000).

Acute
effects
among
experimental
animals
include
general
weight
loss,
liver
pathology,
skin
lesions,
liver,
thymus,
splenic,
and
pancreatic
atrophy
and
dysfunction,
as
well
as
central
nervous
system
abnormalities.
The
lethal
potency
of
TCDD
varies
greatly
among
species
and
the
toxicity
of
different
CDD
isomers
also
varies
greatly.
Guinea
pigs
are
among
the
most
sensitive
species,

where
TCDD
LD50
values
range
from
0.6
to
19
µ
g/
kg.
Hamsters
are
among
the
least
sensitive
species
tested,
with
LD50
values
for
TCDD
ranging
from
1,157
to
5,051
µ
g/
kg.
(
USEPA
1985).

Many
of
the
effects
of
2,3,7,8­
TCDD
are
associated
with
relatively
high
doses,
but
several
significant
adverse
effects
such
as
effects
on
the
developing
immune,
nervous,
and
reproductive
systems
are
observed
at
maternal
body
burdens
which
are
close
to
those
present
in
the
background
human
population
(
Birnbaum
and
Tuomisto,
2000).
Further,
as
noted
by
Steenland
et
al.
(
2004),
dose­
response
assessments
conducted
for
TCDD
and
cancer
indicate
that
TCDD
exposure
levels
close
to
those
in
the
general
population
may
be
carcinogenic
as
well.
Therefore,

at
doses
close
to
those
of
background,
TCDD
has
been
implicated
in
both
carcinogenic
and
non
­

carcinogenic
effects.

The
limited
data
for
other
CDDs
indicate
that
these
chemicals
produce
the
same
acute
effects
as
TCDD
in
a
given
species,
but
the
required
doses
are
higher.
Humans
have
been
exposed
to
herbicides
and
other
chlorinated
chemicals
containing
TCDD
as
a
contaminant.
The
symptoms
of
toxicity
in
many
cases
are
similar
to
those
observed
in
animals,
with
exposure
leading
to
altered
liver
function
and
lipid
metabolism,
porphyria
cutanea
tarda,
neurotoxicity,
pathologic
changes
in
hematologic
parameters,
and
skin
lesions.
Although
some
signs
of
toxicity
such
as
chloracne
are
Page
7
of
22
attributed
to
the
CDDs,
other
signs
may
arise,
at
least
in
part,
from
the
other
chemicals
in
which
CDDs
are
minor
contaminants.
Chloracne,
which
is
characterized
by
comedones
(
blackheads),

keratin
cysts,
pustules,
papules,
and
abscesses,
is
a
classical
sign
of
high
dose
2,3,7,8­
TCDD
exposure
in
humans.
Chloracne
can
be
caused
by
ingestion,
inhalation,
or
skin
contact
with
CDDs
(
USEPA
1980).
In
1991,
Greenlee
et
al.
(
as
cited
in
Schmidt
1992)
identified
two
dioxinresponsive
genes
in
human
skin
cells
that
may
be
involved
in
dioxin­
induced
chloracne.

Treatment
of
monkeys
or
hairless
mice
with
2,3,7,8­
TCDD
produced
lesions
on
the
face
that
were
similar
to
chloracne
lesions
seen
in
humans
(
ATSDR
1989).

A
full
spectrum
of
developmental
toxicity
is
observed
in
experimental
animals
exposed
to
TCDD,

including
reduced
prenatal
and
post­
natal
viability,
alterations
in
development
of
reproductive
organs,
delay
in
onset
of
puberty
in
the
male
rat,
and
altered
sexual
differentiation
in
the
female
rat
(
USEPA,
2000).
Many
of
these
effects
result
from
only
a
single
low
dose
exposure
at
a
discrete
time
point
during
fetal
development.

In
adult
animals,
developmental
and
reproductive
toxicity
is
also
observed,
and
includes
decreased
fertility,
decreased
litter
size,
and
inability
to
maintain
pregnancy
in
female
rats,
and
decreased
testis
and
accessory
sex
organ
weights,
abnormal
testicular
morphology,
decreased
spermatogenesis,
and
reduced
fertility
in
male
rats
(
USEPA,
2000).
Studies
in
rats
have
indicated
that
a
no­
observable­
adverse­
effect
level
(
NOAEL)
for
reproductive
effects
may
be
as
low
as
0.001
µ
g/
kg/
day.
Reproductive
effects
in
rabbits,
including
increases
in
abortions
and
resorptions,

have
been
observed
at
the
0.25
µ
g/
kg/
day
level.
Spontaneous
abortions
occurred
in
two­
thirds
of
monkeys
fed
2,3,7,8­
TCDD
at
levels
of
0.0015
or
0.01
µ
g/
kg/
day
for
7
months.
In
a
3­

generation
reproductive
toxicity
study
in
rats,
the
lowest
dietary
dose
(
0.001
µ
g/
kg/
day)
produced
dilated
renal
pelvis,
decreased
fetal
weight,
and
changes
in
the
gestational
index
(
ATSDR
1989).

The
developmental
effects
observed
in
experimental
animals
are
indicative
of
the
potential
for
developmental
and
reproductive
toxicity
in
humans,
based
on
the
phylogenetic
conservation
of
the
Ah
receptor
among
species
including
humans,
and
the
incorporation
of
this
tenet
into
the
EPA's
risk
assessment
guidelines
for
developmental
toxicity
(
USEPA,
1991b).

3.2
Mutagenicity
and
Carcinogenicity
Page
8
of
22
Mutagenicity
studies
with
TCDD
have
shown
that
the
chemical
is
not
a
direct
acting
genotoxic
agent
(
USEPA,
2000).
TCDD
has
been
shown
to
be
negative
in
the
Ames
Salmonella
assay
and
does
not
form
DNA
adducts
in
vivo
or
in
vitro.
The
National
Toxicology
Program
(
1984)

declared
TCDD
to
be
a
non­
mutagen
using
their
standard
battery
of
mutagenicity
assays.
In
human
populations
exposed
accidentally
or
occupationally
to
TCDD,
there
is
no
consistent
evidence
for
increased
frequencies
of
chromosomal
aberrations
(
USEPA,
2000).
Therefore,

TCDD
is
designated
as
nongenotoxic
based
upon
the
negative
results
from
assays
measuring
potential
DNA
damage,
and
the
significant
tumor
promoting
but
not
initiating
potential
of
TCDD.

Although
classified
as
a
nonmutagen,
TCDD,
and
by
inference
other
dioxin­
like
compounds
including
coplanar
PCBs,
are
described
as
potential
multisite
carcinogens
in
the
more
highly
exposed
human
populations
that
have
been
studied,
consisting
primarily
of
adult
males.
There
is
adequate
evidence
that
2,3,7,8­
TCDD
is
a
carcinogen
in
laboratory
animals
based
on
long­
term
bioassays
conducted
in
both
sexes
of
rats
and
mice.
All
studies
have
produced
positive
results,

leading
to
conclusions
that
TCDD
is
a
multistage
carcinogen
increasing
the
incidence
of
tumors
at
sites
distant
from
the
site
of
treatment
(
USEPA,
2000).
While
several
mechanisms
have
been
proposed
to
explain
the
carcinogenic
action
of
TCDD,
further
research
is
necessary
to
elucidate
a
detailed
mechanistic
model
for
any
particular
carcinogenic
response
in
animals
or
in
humans
(
USEPA,
2000).

In
1985,
EPA
classified
2,3,7,8­
TCDD
and
related
compounds
as
"
probable"
human
carcinogens
based
on
the
available
data.
Since
that
time,
the
database
relating
to
the
carcinogenicity
of
dioxin
and
related
compounds
has
grown
and
strengthened
considerably.
As
noted
by
the
International
Agency
for
Research
on
Cancer
(
IARC,
1997),
although
the
epidemiologic
data
for
2,3,7,8­
TCDD
was
limited
with
respect
to
supporting
a
causal
association
between
exposure
to
2,3,7,8­
TCDD
and
cancer,
the
overall
weight
of
the
evidence
including
human,
animal,
and
mechanistic
data
was
sufficient
to
characterize
2,3,7,8­
TCDD
as
a
"
known"

human
carcinogen.
A
similar
conclusion
has
also
been
stated
in
the
addendum
to
the
ninth
report
on
carcinogens
issued
by
the
National
Toxicology
Program
(
NTP,
2001).
Other
dioxin­
like
compounds
are
characterized
as
"
likely"
human
carcinogens
primarily
on
the
basis
of
the
inference
that,
based
on
toxic
equivalency,
that
they
would
behave
in
humans
as
2,3,7,8­
TCDD
does.

At
this
time,
the
knowledge
of
the
mechanism
of
action
of
dioxin,
receptor
theory,
and
the
Page
9
of
22
available
dose­
response
data
do
not
firmly
establish
a
scientific
basis
for
replacing
a
linear
procedure
for
estimating
cancer
potency.
Therefore,
for
purposes
of
cancer
risk
assessment,
the
Agency
is
using
the
currently
published
slope
factor
of
1.56
E+
5
(
mg/
kg/
day)­
1
for
the
2,3,7,8
congener
(
USEPA,
1985).

In
addition
to
the
2,3,7,8
TCDD
isomer,
two
hexachloro
CDD
isomers
(
1,2,3,6,7,8­
and
1,2,3,7,8,9­
hexachlorodibenzo­
p­
dioxin)
were
tested
in
Osborne­
Mendel
rats
and
B6C3F1
mice
by
the
National
Toxicology
Program
(
NTP,
1980).
Fifty
rats
and
50
mice
of
each
sex
were
administered
the
HxCDD
isomers
suspended
in
a
vehicle
of
9:
1
corn
oil­
acetate
2
days
per
week
for
104
weeks
at
doses
of
1.25,
2.5,
or
5
µ
g/
kg/
wk
for
rats
and
male
mice
and
2.5,
5,
or
10
µ
g/
kg/
wk
for
female
mice.
Under
the
conditions
of
this
bioassay,
the
HxCDD
isomer
mixture
administered
by
gavage
was
carcinogenic,
causing
increased
incidences
of
hepatocellular
carcinomas
or
neoplastic
nodules
in
female
Osborne­
Mendel
rats
and
inducing
hepatocellular
carcinomas
and
adenomas
in
male
and
female
B6C3F1
mice.
HCDD
was
not
demonstrated
to
be
carcinogenic
for
male
rats.
However,
when
administered
by
the
dermal
route
to
Swiss
Webster
mice
(
0.01
µ
g
suspended
in
0.1
ml
acetone
applied
to
the
backs
of
30
mice
of
each
sex
3
days
per
week
for
104
weeks)
there
was
no
evidence
of
carcinogenicity
(
NTP,
1982
a,
b).
Administration
of
1,2,3,4,6,7,8
heptachlorodibenzo­
p­
dioxin
to
female
rats
by
gavage
was
shown
to
result
in
increased
incidence
of
lung
tumors
(
Rozman,
2000).
A
recent
study
also
conducted
by
NTP
(
NTP,
2004)
examined
toxicity
and
carcinogenicity
of
2,3,4,7,8­
pentachlorodibenzofuran
(
PeCDF)
in
female
Sprague­
Dawley
rats.
Groups
of
81
rats
were
administered
PeCDF
in
corn
oil:
acetone
at
doses
of
6,
20,
44,
92,
and
200
ng/
kg
PeCDF
for
up
to
104
weeks.
Up
to
10
rats/
group
were
evaluated
at
14,
31,
and
53
weeks.
At
14
and
53
weeks,
hepatocyte
proliferation
indices
were
significantly
higher
at
the
200
ng/
kg
dose
vs.
time­
matched
controls.
Increased
incidence
of
hepatocellular
adenoma
and
cholangiocarcinoma
were
observed
at
2
years
at
the
200
ng/
kg
dose,
as
was
increased
incidence
of
gingival
squamous
cell
carcinoma
of
the
oral
mucosa.

A
study
of
the
health
records
of
5172
workers
exposed
to
2,3,7,8­
TCDD
at
a
dozen
chemical
plants
indicated
that
workers
were
15%
more
likely
to
die
of
cancer
than
the
general
population.

Records
on
1520
workers
whose
exposures
began
at
greater
than
30
years
ago
­
when
plant
dioxin
levels
were
typically
much
higher
than
today
­
showed
9
times
the
normal
rate
for
one
particular
cancer,
soft­
tissue
sarcoma
(
Fingerhut
et
al.
1991,
as
cited
in
Schmidt
1992).
A
similar
study
in
1583
pesticide
workers
showed
that,
compared
with
the
general
population,
2,3,7,8­

TCDD­
exposed
workers
experienced
a
24%
higher
rate
of
death
from
all
cancers.
Among
Page
10
of
22
workers
with
more
than
20
years'
exposure,
the
cancer
death
rate
increased
to
87%
above
normal
(
Manz
et
al.
1991,
as
cited
in
Schmidt
1992).
Other
studies
have
found
inadequate
or
equivocal
evidence
for
the
carcinogenicity
of
2,3,7,8­
TCDD
in
humans
(
NTP
1989;
Schmidt
1992).

3.3
Toxic
Equivalency
Factors
(
TEFs)
and
Toxic
Equivalency
(
TEQ)

CDDs/
CDFs
present
in
PCP
present
a
unique
case
for
purposes
of
risk
characterization
that
differs
from
the
Office
of
Pesticide
Programs'
usual
approach.
The
17
CDD/
CDF
congeners
are
produced
as
contaminants
in
the
manufacture
of
technical
grade
PCP.
All
of
these
congeners
have
chlorine
substitution
in
at
least
the
2,3,7,
and
8
positions,
thus
imparting
these
contaminants
with
"
dioxin
like"
activity.
Thus,
all
must
be
considered
in
the
risk
assessment
for
the
contaminants
of
PCP.

The
concept
of
toxic
equivalency
factors
(
TEFs)
has
been
developed
to
facilitate
risk
assessment
of
exposure
to
chemical
mixtures
of
CDDs/
CDFs.
In
this
procedure,
individual
TEFs
are
assigned
to
the
17
CDDs/
CDFs.
These
values
have
been
published
by
both
the
USEPA
and
the
World
Health
Organization
(
Van
den
Berg
et
al.,
1998,
1998;
U.
S.
EPA,
1989)
and
are
based
on
assigning
relative
values
in
relation
to
the
most
studied
and
one
of
the
most
toxic
congeners,
2,3,7,8­
TCDD,
which
is
assigned
a
TEF
value
of
1.0.
Multiplying
the
exposure
concentration
of
individual
congeners
by
their
respective
TEFs
yields
a
toxic
equivalent
TEQ
for
each
congener,
which,
when
summed
for
all
the
congeners
of
the
mixture,
gives
the
TEQ
concentration
for
that
mixture.

In
the
case
of
PCP,
the
TEQ
concentration
is
defined
as
the
2,3,7,8­
TCDD
equivalent
concentration
of
CDDs/
CDFs.
It
is
estimated
by
multiplying
the
mass
concentrations
of
2,3,7,8­
CDDs/
CDFs
by
the
corresponding
TEFs
established
by
the
World
Health
Organization
(
WHO)
in
1998
(
Van
den
Berg
et
al.,
1998).
A
CDD/
CDF
TEQ
value
of
0.616
mg
TEQ/
kg
for
technical
PCP
was
used
in
this
assessment.
This
value
represents
the
weighted
combined
average
dioxin
and
furan
concentrations
in
PCP
manufactured
from
January
2000
to
April
2004
for
the
two
industrial
facilities
in
the
United
States
manufacturing
technical
grade
PCP.
This
TEQ
was
developed
using
the
WHO­
TEF
weighting
scheme.
The
development
of
the
TEQ
is
discussed
in­
depth
in
the
addendum
to
the
CDD/
CDF
Product
Chemistry
Chapter
for
the
PCP
RED.
The
calculate
TEQ
factor
of
0.616
mg/
kg
was
then
applied
to
the
PCP
absorbed
doses
to
develop
CDDs/
CDFs
exposure
doses
for
the
handler
and
Page
11
of
22
postapplication
cancer
risk
assessments.
This
method
assumes
that
CDDs/
CDFs
in
PCP
are
absorbed
at
the
same
rate
as
PCP.

For
CDDs/
CDFs,
the
body
burden
approach
appears
to
be
the
most
practical
dosimetric
for
expressing
the
effects
of
CDDs/
CDFs
across
species
(
DeVito
and
Birnbaum,
1995;
Birnbaum
and
Tuomisto,
2000).
This
approach
takes
into
account
the
large
differences
in
half­
life
of
these
chemicals
between
animal
species
and
humans.
While
it
is
recognized
that
both
carcinogenic
and
non­
carcinogenic
effects
can
occur
from
exposure
to
CDDs/
CDFs
at
background
levels
(
Birnbaum
and
Tuomisto,
2000;
Steenland
et
al.,
2004),
because
of
the
expression
of
the
carcinogenic
potency
of
CDDs/
CDFs
as
a
linear
term,
this
would
by
default
be
the
risk
of
most
concern
from
exposure
to
CDDs/
CDFs,
still
recognizing
that
non­
carcinogenic
effects
could
occur
at
similar
exposure
levels.

3.4
FQPA
Considerations
Under
the
Food
Quality
Protection
Act
(
FQPA),
P.
L.
104­
170,
which
was
promulgated
in
1996
as
an
amendment
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
was
directed
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children"
from
aggregate
exposure
to
a
pesticide
chemical
residue.
The
law
further
states
that
in
the
case
of
threshold
effects,
for
purposes
of
providing
this
reasonable
certainty
of
no
harm,
"
an
additional
tenfold
margin
of
safety
for
the
pesticide
chemical
residue
and
other
sources
of
exposure
shall
be
applied
for
infants
and
children
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
data
with
respect
to
exposure
and
toxicity
to
infants
and
children.
Notwithstanding
such
requirement
for
an
additional
margin
of
safety,
the
Administrator
may
use
a
different
margin
of
safety
for
the
pesticide
residue
only
if,
on
the
basis
of
reliable
data,
such
margin
will
be
safe
for
infants
and
children."

It
is
recognized
that
infants
and
children
are
an
important
sensitive
population
in
risk
assessment
because
they
may
be
more
highly
exposed
than
adults
given
their
lower
body
weights.
That
is,
for
a
given
level
of
exposure,
children
will
have
a
higher
exposure
on
a
per
kg
body
weight
basis
than
an
adult.
However,
uses
of
pentachlorophenol
involving
potential
contact
with
food
or
feed
were
Page
12
of
22
restricted
in
the
1980'
s
(
USEPA,
1984)
such
that
the
chemical
was
not
allowed
for
such
uses
subsequent
to
this
restriction.
Therefore,
dietary
exposure
to
the
dioxin/
furan
contaminants
from
PCP­
treated
wood
is
not
expected
and
FQPA
considerations
will
not
apply
in
this
case.
However,

any
issues
with
respect
to
sensitivity
as
applied
to
the
wood
preservative
uses
of
PCP
will
be
taken
into
consideration
in
estimation
of
risk.

TABLE
1
Page
13
of
22
TOXICITY
EQUIVALENCY
FACTORS
FOR
DIOXIN­
LIKE
COMPOUNDS
a
CDD
congener
TEF
CDF
Congener
TEF
2,3,7,8­
TCDD
1.0
2,3,7,8­
TCDF
0.1
1,2,3,7,8­
PeCDD
1.0
1,2,3,7,8­
PeCDF
0.05
1,2,3,4,7,8­
HxCDD
0.1
2,3,4,7,8­
PeCDF
0.5
1,2,3,6,7,8­
HxCDD
0.1
1,2,3,4,7,8­
HxCDF
0.1
1,2,3,7,8,9
­
HxCDD
0.01
1,2,3,6,7,8­
HxCDF
0.1
1,2,3,4,6,7,8,9­
OCDD
0.0001
1,2,3,7,8,9­
HxCDF
0.1
2,3,4,6,7,8­
HxCDF
0.1
1,2,3,4,6,7,8­
HpCDF
0.01
1,2,3,4,7,8,9­
HpCDF
0.01
1,2,3,4,6,7,8,9­

OCDF
0.0001
Note:

(
a).
The
TEF
values
are
taken
from
the
World
Health
Organization's
(
WHO)
revised
list
for
TEFs,
published
in
1998
(
Van
den
Berg
et
al.,
1998).
Page
14
of
22
4.0
EXPOSURE
ASSESSMENT
The
purpose
of
the
exposure
assessment
is
to
estimate
the
magnitude
of
potential
chemical
intake
for
various
receptors.
Detailed
Exposure
to
the
CDD
and
CDF
contaminants
in
PCP
is
addressed
in
detail
in
a
separate
document
(
Aviado,
2004).
Here,
only
summary
information
from
that
document
is
provided
for
clarity
in
the
risk
assessment.

4.1
Identification
of
Potential
Receptor
Populations
The
exposure
scenarios
developed
for
this
RED
Chapter
are
representative
of
potential
occupational
exposures
to
the
chemicals
of
concern
over
a
long­
term
(
>
6
months)
exposure
duration
and
is
focused
primarily
on
cancer
risk.
EPA
has
determined
that
there
are
potential
exposures
to
CDDs/
CDFs
for
mixers,
loaders,
applicators,
and
other
handlers
during
typical
pressure
treatment
use­
patterns
associated
with
the
restricted
use
of
PCP
by
certified
applicators
in
industrial
settings.
Summary
results
are
presented
here.

4.1.1
Occupational
Handlers
Primary
Occupational
Handlers
Handler
exposure
to
PCP
wood
preservatives,
as
product
concentrates
and
treatment
solutions,

results
in
potential
exposure
to
CDDs/
CDFs
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
submitted
by
the
Pentachlorophenol
Task
Force
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.

The
LADDs
for
the
CDDs/
CDFs
cancer
risk
assessment
are
derived
from
the
absorbed
long­
term
doses
for
PCP
adjusted
by
the
0.616
mg
TEQ/
kg
factor
to
yield
absorbed
long­
term
doses
for
CDDs/
CDFs
which
are
then
amortized
over
a
lifetime.
Exposure
frequency
is
assumed
to
be
250
working
days
per
year
(
i.
e.,
five
days
per
week,
50
days
per
year).
This
is
a
standard
Agency
Page
15
of
22
assumption
for
days
worked
per
year.
Exposure
duration
was
assumed
to
be
40
years
and
is
a
conservative
standard
value
used
by
OPP
to
represent
a
working
lifetime.
Lifetime
is
assumed
to
be
75
years.
This
is
the
recommended
value
for
the
U.
S.
population,
as
cited
in
EPA's
Exposure
Factors
Handbook
(
U.
S.
EPA,
1997)
and
typically
used
in
OPP
assessments
as
a
standard
value.

Cancer
risk
was
calculated
by
multiplying
the
CDDs/
CDFs
LADD
by
the
cancer
slope
factor
of
1.56E+
05
(
mg/
kg/
day)
­
1
A
cancer
risk
greater
than
E­
6
is
of
concern
to
be
mitigated
and
risks
greater
than
E­
4
are
generally
considered
unacceptable.
All
of
the
assessed
occupational
handler
scenarios
are
in
the
range
of
E­
4
for
the
pressure
treatment
operator
handling
the
crystalline
product
(
1.1E­
4)
and
the
liquid
formulation
(
2.3E­
4),
and
the
pressure
treatment
assistant
handling
the
crystalline
product
(
4.2E­
4)
and
the
liquid
formulation
(
6.7E­
4).
The
Agency
will
seek
ways
to
mitigate
the
risks,
to
the
extent
that
it
is
practical
and
economically
feasible,
to
lower
the
risks
to
E­
6
or
less.

Occupational
Postapplication
Exposure
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
freshlytreated
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
(
PTF,
1999)

further
detailed
in
the
PCP
RED
Human
Exposure
Chapter:

(
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
inservice
poles.
Biomonitoring
data
from
a
worker
exposure
study
on
utility
linemen
entitled
Occupational
Exposure
of
Electrical
Utility
Linemen
to
Pentachlorophenol.
(
Thind
et
al.,
1991)
were
used
to
characterize
chronic
or
long­
term
exposure
from
absorbed
doses
of
CDDs/
CDFs
in
PCP
based
on
measured
PCP
residue
levels
in
monitored
worker
urine
samples.
As
noted
in
this
Page
16
of
22
published
study,
the
work
activities
of
the
linemen
include
frequent
climbing
of
new
or
in­
service
PCP­
treated
poles,
which
require
significant
skin
contact
to
PCP­
containing
oils
which
run
down
the
surface
of
the
telephone
poles.
The
following
postapplication
exposure
scenario
represents
electrical
utility
workers:

(
4)
Pole
Installers
(
Electrical
Utility
Linemen).

For
both
postapplication
pressure
treatment
and
electrical
utility
linemen
scenarios,
the
lifetime
average
daily
doses
(
LADDs)
for
the
cancer
risk
assessment
are
based
on
the
absorbed
doses
derived
from
the
data
on
PCP
residues
in
worker
urine
samples
from
both
biomonitoring
studies
detailed
in
the
PCP
RED
Human
Exposure
Chapter
(
PTF,
1999
and
Thind
et
al.,
1991).
The
dose
and
risk
calculations
for
the
cancer
assessment
were
conducted
as
described
in
the
occupational
exposure
chapter.

None
of
the
assessed
occupational
postapplication
scenarios
exceeded
the
Agency's
level
of
concern
(
i.
e.,
E­
4)
for
cancer
risks.
Cancer
risks
are
as
follows:
the
pressure
treatment
loader
operator
(
9.5E­
5),
pressure
treatment
test
borer
(
8.4E­
5),
general
helpers
(
4.9E­
5)
and
electrical
utility
linemen
(
3.4E­
5).
The
Agency
will
seek
ways
to
mitigate
the
risks,
to
the
extent
that
it
is
practical
and
economically
feasible,
to
lower
the
risks
to
E­
6
or
less.

4.1.2
Residential
Receptors
Residential
postapplication
exposure
to
CDD/
CDF
contaminants
of
PCP
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
CDD/
CDF
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
Page
17
of
22
around
these
pole
structures
would
not
normally
occur
and
any
incidental
exposure
would
therefore
be
negligible.

5.0
RISK
CHARACTERIZATION
As
noted
above,
carcinogenic
risks
have
been
assessed
using
the
published
cancer
slope
factor
for
TCDD.
As
noted
above
in
this
document,
at
doses
close
to
those
of
background,
TCDD
has
been
implicated
in
both
carcinogenic
and
non
­
carcinogenic
effects.
Non­
cancer
risks
have
not
been
separately
addressed
since
the
expression
of
carcinogenic
potency
of
CDDs/
CDFs
as
a
linear
term
would
be,
by
default,
the
risk
of
most
concern
and
anticipated
to
be
protective
of
non­
cancer
risks.

Occupational
Cancer
Risks
from
Absorbed
Doses
of
CDD/
CDF
Impurities
in
PCP
For
primary
occupational
handlers,
the
assessed
exposure
scenarios
were
in
the
range
of
E­
4
for
the
pressure
treatment
operator
handling
the
crystalline
product
(
1.1E­
4)
and
the
liquid
formulation
(
2.3E­
4),
and
the
pressure
treatment
assistant
handling
the
crystalline
product
(
4.2E­

4)
and
the
liquid
formulation
(
6.7E­
4).

None
of
the
assessed
occupational
postapplication
scenarios
exceeded
the
Agency's
level
of
concern
(
i.
e.,
E­
4)
for
cancer
risks.
Cancer
risks
are
in
the
E­
5
range
for
all
scenarios:
the
pressure
treatment
loader
operator
(
9.5E­
5),
pressure
treatment
test
borer
(
8.4E­
5),
general
helpers
(
4.9E­
5)
and
electrical
utility
linemen
(
3.4E­
5).

6.0
UNCERTAINTY
ANALYSIS
When
assessing
risks
from
exposure
to
the
dioxins
and
dioxin­
like
compounds,
"
knowing
the
increment
[
exposure]
relative
to
background
may
help
to
understand
the
impact
of
the
incremental
exposure"
(
USEPA,
2000).
In
this
sense,
then,
in
order
to
properly
assess
risk,
one
should
have
an
adequate
characterization
of
"
background"
dioxin
exposures,
a
discussion
of
the
percent
Page
18
of
22
increase
over
background
for
the
exposure
of
interest,
and
a
policy
statement
that
describes
at
what
point
the
increases
over
background
become
significant
in
terms
of
risk.
Risk
from
exposure
to
dioxins
in
pentachlorophenol­
treated
wood
should
be
considered
in
the
context
of
all
sources
to
which
a
person
may
be
exposed
to
dioxins.
According
to
the
most
current
data,
intake
levels
of
dioxin
from
food
sources
are
estimated
at
approximately
1
pg
TEQ/
kg
/
day,
but
this
is
an
average
value
and
may
not
be
inclusive
of
all
subpopulations
(
USEPA,
2000),
where
additional
exposures
may
occur
as
a
result
of
contamination
incidents
or
exposures
from
discrete
sources.

While
the
current
assessment
has
estimated
occupational
exposures
to
dioxins
and
dioxin­
like
contaminants
from
contact
with
pentachlorophenol­
treated
wood,
the
ORD
reassessment
only
addresses
PCP
in
treated
wood
as
a
reservoir
source
that
could
contribute
to
overall
background
exposures
through
possible
release
of
CDDs/
CDFs
from
the
wood
while
it
is
still
in
service.
The
ORD
reassessment
does
not
explicitly
quantify
occupational
exposures
(
except
in
the
context
of
the
evaluation
of
epidemiological
studies
where
significant
occupational
exposures
are
known
to
have
occurred
in
the
past),
but
the
results
in
this
assessment
suggest
that
the
potential
exposures
faced
by
individuals
in
occupations
associated
with
treating
wood
and
PCP,
and
then
putting
this
treated
wood
in
service,
could
face
dioxin
exposures
comparable
to
background
exposures
for
this
important
class
of
compounds
(
USEPA,
2000).

From
the
analysis
of
occupational
exposure
to
the
"
dioxin
like"
CDD
and
CDF
contaminants
of
PCP,
it
is
apparent
that
the
most
significant
exposures
occur
within
the
occupational
setting,

particularly
for
those
individuals
involved
in
handling
treated
lumber
in
the
workplace.
However,

exposures
identified
in
the
occupational
setting
in
the
present
assessment
need
to
be
considered
within
the
context
of
the
assumptions
made.

The
data
used
to
develop
the
occupational
scenarios
and
estimates
of
exposure
to
CDDs/
CDFs
in
PCP
were
from
limited
available
study
data
on
PCP.
The
handler/
postapplication
assessments
for
pressure
treatment
plant
workers
were
based
on
data
for
PCP
in
the
study
entitled
Inhalation
Dosimetry
and
Biomonitoring
of
Worker
Exposure
to
Pentachlorophenol
During
Pressure­

Treatment
of
Lumber
(
PTF,
1999).
The
postapplication
assessment
for
pole
installers
utilized
published
biomonitoring
data
in
the
industrial
hygiene
study
entitled
Occupational
Exposure
of
Electrical
Utility
Linemen
to
Pentachlorophenol
(
Thind
et
al.,
1991)
to
estimate
potential
worker
dermal
exposure.
Specific
limitations
related
to
these
studies
are
noted
in
the
PCP
RED
Human
Exposure
Chapter.

Occupational
postapplication
scenarios
were
developed
for
workers
engaged
in
post­
treatment
Page
19
of
22
handling
of
wood
in
a
pressure
treatment
plant,
and
for
electrical
utility
linemen
involved
in
utility
pole
installation.
Other
PCP
exposures
not
addressed
in
this
study
include
postapplication
exposure
to
workers
engaged
in
construction
fabrication
of
PCP­
treated
timbers/
lumber.

Activities
involving
cutting
and
sanding
of
PCP­
treated
wood
may
cause
dermal,
inhalation
or
oral
ingestion
exposure
concerns
for
CDDs/
CDFs
in
PCP.

An
additional
area
of
uncertainty
involves
the
selection
of
the
TEQ
factor
of
0.616
mg
TEQ/
kg
for
the
occupational
assessment,
as
derived
from
the
analyses
conducted
on
EPA
industry
monitoring
data
from
KMG­
Bernuth
and
Vulcan
Chemicals
for
manufactured
technical
PCP
in
production
years
2000­
2004.
The
TEQ
factor
was
calculated
based
on
both
measured
and
predicted
values
for
certain
congener
concentrations
using
linear
regression
analysis.
As
per
the
CDDs/
CDFs
Product
Chemistry
Chapter
addendum
(
Shamim,
2005)
a
linear
regression
analysis
of
KMG
HpCDD
on
OCDCC
and
HpCDF
on
OCDF,
to
calculate
the
concentrations
of
octa
congeners
of
Vulcan
resulted
in
a
very
poor
linear
relationship
(
R2
=
0.22
for
dioxins
and
R2
=
0.46
for
the
furan
congeners)
yielding
a
high
degree
of
uncertainty
built
into
the
total
TEQ
calculations.

The
current
occupational
assessment
presents
only
potential
cancer
risks.
A
limitation
is
that
non­
cancer
exposure
risks
have
not
been
separately
addressed.
The
expression
of
carcinogenic
potency
of
CDDs/
CDFs
as
a
linear
term
would
be,
by
default,
the
risk
of
most
concern
and
anticipated
to
be
protective
of
non­
cancer
risks.
Page
20
of
22
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