Document ID: EPA-HQ-RCRA-2004-0010-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-07-28T04:00Z

Lead
and
compounds
(
inorganic)
(
CASRN
7439­
92­
1)

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Reference
Dose
for
Chronic
Oral
Exposure
(
RfD)

0277
Lead
and
compounds
(
inorganic);
CASRN
7439­
92­
1
Human
health
assessment
information
on
a
chemical
substance
is
included
in
IRIS
only
after
a
comprehensive
review
of
chronic
toxicity
data
by
U.
S.
EPA
health
scientists
from
several
program
offices,
regional
offices,
and
the
Office
of
Research
and
Development.
Sections
I
(
Chronic
Health
Hazard
Assessments
for
Noncarcinogenic
Effects)
and
II
(
Carcinogenicity
Assessment
for
Lifetime
Exposure)
present
the
positions
that
were
reached
during
the
review
process.
Supporting
information
and
explanations
of
the
methods
used
to
derive
the
values
given
in
IRIS
are
provided
in
the
guidance
documents
located
on
the
IRIS
website
at
http://
www.
epa.
gov/
iriswebp/
iris/
backgr­
d.
htm.

STATUS
OF
DATA
FOR
Lead
and
compounds
(
inorganic)

File
First
On­
Line
03/
01/
1988
Category
(
section)
Status
Last
Revised
Oral
RfD
Assessment
(
I.
A.)
discussion
07/
08/
2004
Inhalation
RfC
Assessment
(
I.
B.)
no
data
Carcinogenicity
Assessment
(
II.)
on­
line
11/
01/
1993
_
I.
Chronic
Health
Hazard
Assessments
for
Noncarcinogenic
Effects
_
I.
A.
Reference
Dose
for
Chronic
Oral
Exposure
(
RfD)

Substance
Name
­­
Lead
and
compounds
(
inorganic)
CASRN
­­
7439­
92­
1
Section
I.
A.
Last
Revised
­­
07/
08/
2004
I
n
general,
the
oral
Reference
Dose
(
RfD)
is
an
estimate
(
with
uncertainty
spanning
perhaps
an
order
of
magnitude)
of
a
daily
exposure
to
the
human
population
(
including
sensitive
subgroups)
that
is
likely
to
Chronic
Health
Hazards
for
Non­
Carcinogenic
Effects
Reference
Dose
for
Chronic
Oral
Exposure
(
RfD)

­
Oral
RfD
Summary
­
Principal
and
Supporting
Studies
­
Uncertainty
and
Modifying
Factors
­
Additional
Studies/
Comments
­
Confidence
in
the
Oral
RfD
­
EPA
Documentation
and
Review
Reference
Concentration
for
Chronic
Inhalation
Exposure
(
RfC)

­
Inhalation
RfC
Summary
­
Principal
and
Supporting
Studies
­
Uncertainty
and
Modifying
Factors
­
Additional
Studies/
Comments
­
Confidence
in
the
Inhalation
RfC
­
EPA
Documentation
and
Review
Carcinogenicity
Assessment
for
Lifetime
Exposure
Evidence
for
Human
Carcinogenicity
­
Weight­
of­
Evidence
Characterization
­
Human
Carcinogenicity
Data
­
Animal
Carcinogenicity
Data
be
without
an
appreciable
risk
of
deleterious
effects
during
a
lifetime.
The
RfD
is
based
on
the
assumption
that
thresholds
exist
for
certain
toxic
effects
such
as
cellular
necrosis
and
is
expressed
in
units
of
mg/
kg­
day.
Please
refer
to
the
guidance
documents
at
http://
www.
epa.
gov/
iriswebp/
iris/
backgr­
d.
htm
for
an
elaboration
of
these
concepts.
Since
RfDs
can
be
derived
for
the
noncarcinogenic
health
effects
of
substances
that
are
also
carcinogens,
it
is
essential
to
refer
to
other
sources
of
information
concerning
the
carcinogenicity
of
this
chemical
substance.
If
the
U.
S.
EPA
has
evaluated
this
substance
for
potential
human
carcinogenicity,
a
summary
of
that
evaluation
will
be
contained
in
Section
II
of
this
file.

__
I.
A.
1.
Oral
RfD
Summary
Health
effects
associated
with
exposure
to
inorganic
lead
and
compounds
include,
but
are
not
limited
to,
neurotoxicity,
developmental
delays,
hypertension,
impaired
hearing
acuity,
impaired
hemoglobin
synthesis,
and
male
reproductive
impairment.
Importantly,
many
of
lead's
health
effects
may
occur
without
overt
signs
of
toxicity.
Lead
has
particularly
significant
effects
in
children,
well
before
the
usual
term
of
chronic
exposure
can
take
place.
Children
under
6
years
old
have
a
high
risk
of
exposure
because
of
their
more
frequent
hand­
to­
mouth
behavior
(
Centers
for
Disease
Control
and
Prevention
(
CDC),
1991:
http://
www.
cdc.
gov/
nceh/
lead/
publications/
books/
plpyc/
contents.
htm
).

EPA
considered
providing
an
RfD
for
inorganic
lead
in
1985,
and
concluded
that
it
was
inappropriate
to
develop
an
RfD,
as
documented
online
in
the
following
statement
in
1988:

A
great
deal
of
information
on
the
health
effects
of
lead
has
been
obtained
through
decades
of
medical
observation
and
scientific
research.
This
information
has
been
assessed
in
the
development
of
air
and
water
quality
criteria
by
the
Agency's
Office
of
Health
and
Environmental
Assessment
(
OHEA)
in
support
of
regulatory
decision­
making
by
the
Office
of
Air
Quality
Planning
and
Standards
(
OAQPS)
and
by
the
Office
of
Drinking
Water
(
ODW).
By
comparison
to
most
other
environmental
toxicants,
the
degree
of
uncertainty
about
the
health
effects
of
lead
is
quite
low.
It
appears
that
some
of
these
effects,
particularly
changes
in
the
levels
of
certain
blood
enzymes
and
in
aspects
of
children's
neurobehavioral
development,
may
occur
at
blood
lead
levels
so
low
as
to
be
essentially
without
a
threshold.
The
Agency's
RfD
Work
Group
discussed
inorganic
lead
(
and
lead
compounds)
at
two
meetings
(
07/
08/
1985
and
07/
22/
1985)
and
considered
it
inappropriate
to
develop
an
RfD
for
inorganic
lead.

EPA
is
not
providing
a
review
of
current
literature
concerning
the
health
effects
of
lead
at
this
time
(
June,
2004),
given
the
ongoing
effort
of
the
CDC
to
re­
evaluate
the
blood
lead
level
of
concern
(
CDC,
2004:
http://
www.
cdc.
gov/
nceh/
lead/
spotLights/
changeBLL.
htm
).
A
screening­
level
review
of
the
more
recent
toxicology
literature
pertinent
to
noncancer
effects
associated
with
oral
exposure
to
Lead
and
compounds
(
inorganic)
was
conducted
by
an
EPA
contractor
in
September
2002,
and
identified
one
or
more
significant
new
studies
since
the
1985
assessment.
IRIS
users
may
request
the
references
for
those
­
Supporting
Data
for
Carcinogenicity
Quantitative
Estimate
of
Carcinogenic
Risk
from
Oral
Exposure
­
Summary
of
Risk
Estimates
­
Dose­
Response
Data
­
Additional
Comments
­
Discussion
of
Confidence
Quantitative
Estimate
of
Carcinogenic
Risk
from
Inhalation
Exposure
­
Summary
of
Risk
Estimates
­
Dose­
Response
Data
­
Additional
Comments
­
Discussion
of
Confidence
EPA
Documentation,
Review
and,
Contacts
 
Bibliography
 
Revision
History
 
Synonyms
studies
from
the
IRIS
Hotline
at
hotline.
iris@
epa.
gov
or
(
202)
566­
1676.

Current
knowledge
of
lead
pharmacokinetics
indicates
that
risk
values
derived
by
standard
procedures
would
not
truly
indicate
the
potential
risk,
because
of
the
difficulty
in
accounting
for
pre­
existing
body
burdens
of
lead.
Lead
bioaccumulates
in
the
body,
primarily
in
the
skeleton.
Lead
body
burdens
vary
significantly
with
age,
health
status,
nutritional
state,
maternal
body
burden
during
gestation
and
lactation,
etc.
For
this
reason,
and
because
of
the
continued
apparent
lack
of
threshold
(
CDC,
2004:
http://
www.
cdc.
gov/
nceh/
lead/
spotLights/
changeBLL.
htm
),
it
is
still
inappropriate
to
develop
reference
values
for
lead.

The
purpose
of
this
2004
update
is
to
assist
IRIS
users
in
finding
relevant
risk
information
and
risk
assessment
methods
that
have
been
developed
within
EPA
for
media­
specific
applications.
Most
of
these
methods
focus
on
blood
lead
levels,
through
the
development
of
several
media­
specific
lead
exposure
levels
for
risk
management
and
regulatory
purposes.
Further
information
on
these
lead
risk
assessment
methods
and
tools
is
described
in
Section
1.
A.
4.

__
I.
A.
2.
Principal
and
Supporting
Studies
(
Oral
RfD)

Not
applicable.

__
I.
A.
3.
Uncertainty
and
Modifying
Factors
(
Oral
RfD)

Not
applicable.

__
I.
A.
4.
Additional
Studies/
Comments
(
Oral
RfD)

As
noted
above,
EPA
is
not
providing
a
review
of
current
literature
at
this
time.
In
addition
to
information
developed
by
CDC
and
the
Agency
for
Toxic
Substances
and
Disease
Registry
(
ATSDR),
described
below,
EPA
has
developed
a
number
of
lead
exposure
limits
in
support
of
regulatory
decision­
making,
and
has
developed
methods
to
assess
risk
from
lead
in
situations
not
covered
by
these
limits,
also
described
below.

The
CDC
identified
10
µ
g/
dL
as
the
blood
lead
level
of
concern
in
children
in
their
1991
report
"
Preventing
Lead
Poisoning
in
Young
Children"
(
http://
www.
cdc.
gov/
nceh/
lead/
publications/
books/
plpyc/
contents.
htm
),
and
provided
risk
management
options
for
categories
of
blood
lead
levels
higher
than
10
µ
g/
dL.
In
view
of
the
fact
that
health
effects
were
and
continue
to
be
identified
below
the
level
of
concern,
the
CDC
convened
an
Advisory
Committee
on
Childhood
Lead
Poisoning
Prevention
to
consider
whether
the
level
of
concern
should
be
changed.
The
Advisory
Committee's
progress
reports
can
be
found
at
http://
www.
cdc.
gov/
nceh/
lead/
ACCLPP/
acclpp_
main.
htm
.
At
this
time,
CDC
has
not
changed
the
blood
lead
level
of
concern
for
three
reasons
(
March
23,
2004,
http://
www.
cdc.
gov/
nceh/
lead/
spotLights/
changeBLL.
htm
):
 
'
No
effective
clinical
interventions
are
known
to
lower
blood
lead
levels
for
children
with
levels
less
than
10
µ
g/
dL
or
to
reduce
the
risks
for
adverse
developmental
effects.'
`
 
Children
cannot
be
accurately
classified
as
having
blood
lead
levels
above
or
below
10
µ
g/
dL
because
of
the
inaccuracy
inherent
in
laboratory
testing.'
`
 
Finally,
there
is
no
evidence
of
a
threshold
below
which
adverse
effects
are
not
experienced.
Thus,
any
decision
to
establish
a
new
level
of
concern
would
be
arbitrary
and
provide
uncertain
benefits.'

In
addition
to
the
ongoing
CDC
effort,
the
ATSDR
is
mandated
by
Congress
under
CERCLA
(
1980)
and
SARA
(
1986)
to
develop
toxicological
profiles
for
all
hazardous
waste
sites
on
the
National
Priorities
List
(
NPL)
(
PB/
99/
166704,
NTIS
PB­
99­
66704;
http://
www.
atsdr.
cdc.
gov/
toxprofiles/
tp13.
html
).
Lead
is
the
most
common
toxic
metal
at
these
sites.
The
ATSDR
Toxicological
Profile
for
Lead
was
last
updated
in
1999.

EPA
has
developed
a
number
of
lead
exposure
levels
in
support
of
regulatory
decision­
making,
which
limit
the
amount
of
lead
that
can
be
present
in
various
environmental
media.
Under
the
National
Primary
Drinking
Water
Regulations,
EPA
established
a
Maximum
Contaminant
Level
(
MCL)
for
lead
in
drinking
water
due
to
any
source.
Under
the
Toxic
Substances
Control
Act
(
TSCA)
as
amended
by
the
Residential
Lead­
Based
Paint
Hazard
Reduction
Act,
EPA
established
standards
for
lead
in
paint,
house
dust,
and
outdoor
soil.
The
following
links
provide
more
information:

Action
level
for
lead
in
drinking
water:
http://
www.
epa.
gov/
safewater/
mcl.
html#
mcls
Regulation
for
lead
in
paint
housedust,
and
outdoor
soil:
http://
www.
epa.
gov/
oppt/
lead/
pubs/
leadhaz.
htm
National
ambient
air
quality
standard:
http://
www.
epa.
gov/
ttn/
naaqs/

Note
that
additional
relevant
information
will
be
found
by
following
links
provided
at
these
websites,
such
as
dose­
response
relationships
relating
blood
lead
levels
to
changes
in
IQ
(
children)
and
hypertension
(
men).

Due
to
the
likelihood
of
simultaneous
exposure
to
various
sources
of
lead,
EPA
recommends
a
case­
by­
case
evaluation
of
the
relative
contributions
of
relevant
lead
exposures
in
a
particular
setting.
The
Superfund
Program
has
guidelines
for
identifying
lead­
contaminated
soil
(
http://
www.
epa.
gov/
superfund/
programs/
lead/
products.
htm),
and
facilitates
site­
specific
risk
assessments
at
contaminated
waste
sites
on
the
National
Priority
List,
where
the
major
sources
of
soil
contamination
are
activities
such
as
disposal
of
mining
and
manufacturing
wastes
contaminated
with
lead
and
deposition
of
lead
from
air,
rather
than
presence
of
lead­
based
paint
in
residences
(
see:
http://
www.
epa.
gov/
superfund/
programs/
lead/
trwhome.
htm).
The
Superfund
Program
uses
the
Integrated
Exposure
Uptake
Biokinetic
(
IEUBK)
Model
for
Lead
in
Children.
The
IEUBK
Model
provides
estimates
of
the
risk
of
elevated
blood
lead
associated
with
particular
combinations
of
relevant
sources
of
lead
exposure.
This
interactive
model
is
described
in
more
detail
and
provided
for
downloading
at
http://
www.
epa.
gov/
superfund/
programs/
lead/
products.
htm.
Note
that
the
IEUBK
model
was
used
in
direct
support
of
the
lead­
based
paint
regulation
cited
above.

The
Superfund
Program
has
also
developed
an
Adult
Lead
Model,
for
use
when
lead
exposures
to
adults,
especially
pregnant
women,
are
of
greater
concern.
This
model
is
described
and
provided
for
downloading
at
http://
www.
epa.
gov/
superfund/
programs/
lead/
adult.
htm.

EPA
maintains
a
lead
resources
page
(
http://
www.
epa.
gov/
opptintr/
lead/
pubs/
resources.
htm).
Links
are
provided
to
many
other
EPA
offices,
government
agencies,
and
other
organizations
involved
in
efforts
to
reduce
exposure
to
lead
in
the
environment.

__
I.
A.
5.
Confidence
in
Risk
Values
Not
applicable.

__
I.
A.
6.
EPA
Documentation
and
Review
of
the
Oral
RfD
Agency
Completion
Date
 
05/
26/
2004
__
I.
A.
7.
EPA
Contacts
(
Oral
RfD)

Please
contact
the
IRIS
Hotline
for
all
questions
concerning
this
assessment
or
IRIS,
in
general,
at
(
202)
566­
1676
(
phone),
(
202)
566­
1749
(
fax),
or
hotline.
iris@
epa.
gov
(
email
address).

Back
to
top
_
I.
B.
Reference
Concentration
for
Chronic
Inhalation
Exposure
(
RfC)

Substance
Name
­­
Lead
and
compounds
(
inorganic)
CASRN
 
7439­
92­
1
In
general,
the
Reference
Concentration
(
RfC)
is
an
estimate
(
with
uncertainty
spanning
perhaps
an
order
of
magnitude)
of
a
daily
inhalation
exposure
of
the
human
population
(
including
sensitive
subgroups)
that
is
likely
to
be
without
an
appreciable
risk
of
deleterious
effects
during
a
lifetime.
The
RfC
considers
toxic
effects
for
both
the
respiratory
system
(
portal­
of­
entry)
and
for
effects
peripheral
to
the
respiratory
system
(
extrarespiratory
effects).
The
inhalation
RfC
(
generally
expressed
in
units
of
mg/
m3)
is
analogous
to
the
oral
RfD
and
is
likewise
based
on
the
assumption
that
thresholds
exist
for
certain
toxic
effects
such
as
cellular
necrosis.
Inhalation
RfCs
are
derived
according
to
the
Interim
Methods
for
Development
of
Inhalation
Reference
Doses
(
EPA/
600/
8­
88/
066F,
1989)
and
subsequently,
according
to
Methods
for
Derivation
of
Inhalation
Reference
Concentrations
and
Application
of
Inhalation
Dosimetry
(
EPA/
600/
8­
90/
066F,
1994).
Since
RfCs
can
also
be
derived
for
the
noncarcinogenic
health
effects
of
substances
that
are
carcinogens,
it
is
essential
to
refer
to
other
sources
of
information
concerning
the
carcinogenicity
of
this
chemical
substance.
If
the
U.
S.
EPA
has
evaluated
this
substance
for
potential
human
carcinogenicity,
a
summary
of
that
evaluation
will
be
contained
in
Section
II
of
this
file.

__
I.
B.
1.
Inhalation
RfC
Summary
No
RfC
is
available.
See
Section
I.
A.
for
additional
information.

__
I.
B.
2.
Principal
and
Supporting
Studies
(
Inhalation
RfC)

Not
applicable.

__
I.
B.
3.
Uncertainty
and
Modifying
Factors
(
Inhalation
RfC)

Not
applicable.

__
I.
B.
4.
Additional
Studies/
Comments
(
Inhalation
RfC)

Not
applicable.

__
I.
B.
5.
Confidence
in
the
Inhalation
RfC
Not
applicable.

__
I.
B.
6.
EPA
Documentation
and
Review
of
the
Inhalation
RfC
Agency
Completion
Date
­­
Not
applicable.

__
I.
B.
7.
EPA
Contacts
(
Inhalation
RfC)

Please
contact
the
IRIS
Hotline
for
all
questions
concerning
this
assessment
or
IRIS,
in
general,
at
(
202)
566­
1676
(
phone),
(
202)
566­
1749
(
fax),
or
hotline.
iris@
epa.
gov
(
email
address).

Back
to
top
_
II.
Carcinogenicity
Assessment
for
Lifetime
Exposure
Substance
Name
­­
Lead
and
compounds
(
inorganic)
CASRN
­­
7439­
92­
1
Section
II
Last
Revised
­­
II.
A.
introductory
paragraph
revised
07/
08/
2004.
II.
A.
1
­
II.
D.
last
revised
11/
01/
1993
Section
II
provides
information
on
three
aspects
of
the
carcinogenic
assessment
for
the
substance
in
question;
the
weight­
of­
evidence
judgment
of
the
likelihood
that
the
substance
is
a
human
carcinogen,
and
quantitative
estimates
of
risk
from
oral
exposure
and
from
inhalation
exposure.
The
quantitative
risk
estimates
are
presented
in
three
ways.
The
slope
factor
is
the
result
of
application
of
a
low­
dose
extrapolation
procedure
and
is
presented
as
the
risk
per
(
mg/
kg)/
day.
The
unit
risk
is
the
quantitative
estimate
in
terms
of
either
risk
per
µ
g/
L
drinking
water
or
risk
per
µ
g/
cu.
m
air
breathed.
The
third
form
in
which
risk
is
presented
is
a
concentration
of
the
chemical
in
drinking
water
or
air
associated
with
cancer
risks
of
1
in
10,000,
1
in
100,000,
or
1
in
1,000,000.
The
rationale
and
methods
used
to
develop
the
carcinogenicity
information
in
IRIS
are
described
in
the
Risk
Assessment
Guidelines
of
1986
(
EPA/
600/
8­
87/
045)
and
in
the
IRIS
Background
Document.
IRIS
summaries
developed
since
the
publication
of
EPA's
more
recent
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
also
utilize
those
Guidelines
where
indicated
(
Federal
Register
61(
79):
17960­
18011,
April
23,
1996).
Users
are
referred
to
Section
I
of
this
IRIS
file
for
information
on
longterm
toxic
effects
other
than
carcinogenicity.

_
II.
A.
Evidence
for
Human
Carcinogenicity
Note
that
the
National
Toxicology
Program's
Report
on
Carcinogens
Review
Committee
has
recommended
that
lead
and
lead
compounds
be
considered
"
reasonably
anticipated
to
be
human
carcinogens"
(
http://
ntpserver
niehs.
nih.
gov/
NewHomeRoc/
roc11Bkgrnd2003.
html
;
July
2003).
Also,
the
International
Agency
for
Research
on
Cancer
(
IARC)
has
undertaken
a
reevaluation
of
lead's
carcinogenicity
(
http://
monographs.
iarc.
fr/
ENG/
Meetings/
vol87.
php
).

__
II.
A.
1.
Weight­
of­
Evidence
Characterization
Classification
­­
B2;
probable
human
carcinogen
Basis
­­
Sufficient
animal
evidence.
Ten
rat
bioassays
and
one
mouse
assay
have
shown
statistically
significant
increases
in
renal
tumors
with
dietary
and
subcutaneous
exposure
to
several
soluble
lead
salts.
Animal
assays
provide
reproducible
results
in
several
laboratories,
in
multiple
rat
strains
with
some
evidence
of
multiple
tumor
sites.
Short
term
studies
show
that
lead
affects
gene
expression.
Human
evidence
is
inadequate.

__
II.
A.
2.
Human
Carcinogenicity
Data
Inadequate.
There
are
four
epidemiologic
studies
of
occupational
cohorts
exposed
to
lead
and
lead
compounds.
Two
studies
(
Dingwall­
Fordyce
and
Lane,
1963;
Nelson
et
al.,
1982)
did
not
find
any
association
between
exposure
and
cancer
mortality.
Selevan
et
al.
(
1985),
in
their
retrospective
cohort
mortality
study
of
primary
lead
smelter
workers,
found
a
slight
decrease
in
the
total
cancer
mortality
(
SMR=
95).
Apparent
excesses
were
observed
for
respiratory
cancer
(
SMR=
111,
obs=
41,
p>
0.05)
and
kidney
cancer
(
SMR=
204,
obs=
6,
p>
0.05).
Cooper
and
Gaffey
(
1975)
and
Cooper
(
1985
update)
performed
a
cohort
mortality
study
of
battery
plant
workers
and
lead
smelter
workers.
They
found
statistically
significant
excesses
for
total
cancer
mortality
(
SMR=
113,
obs=
344),
stomach
cancer
(
SMR=
168,
obs=
34),
and
lung
cancer
(
SMR=
124,
obs=
109)
in
the
battery
plant
workers.
Although
similar
excesses
were
observed
in
the
smelter
workers,
they
were
not
statistically
significant.
Cooper
and
Gaffey
(
1975)
felt
it
was
possible
that
individual
subjects
were
monitored
primarily
on
the
basis
of
obvious
signs
of
lead
exposure,
while
others
who
showed
no
symptoms
of
lead
poisoning
were
not
monitored.

All
of
the
available
studies
lacked
quantitative
exposure
information,
as
well
as
information
on
the
possible
contribution
from
smoking.
All
studies
also
included
exposures
to
other
metals
such
as
arsenic,
cadmium,
and
zinc
for
which
no
adjustment
was
done.
The
cancer
excesses
observed
in
the
lung
and
stomach
were
relatively
small
(<
200).
There
was
no
consistency
of
site
among
the
various
studies,
and
no
study
showed
any
dose­
response
relationship.
Thus,
the
available
human
evidence
is
considered
to
be
inadequate
to
refute
or
demonstrate
any
potential
carcinogenicity
for
humans
from
lead
exposure.

__
II.
A.
3.
Animal
Carcinogenicity
Data
Sufficient.
The
carcinogenic
potential
of
lead
salts
(
primarily
phosphates
and
acetates)
administered
via
the
oral
route
or
by
injection
has
been
demonstrated
in
rats
and
mice
by
more
than
10
investigators.
The
most
characteristic
cancer
response
is
bilateral
renal
carcinoma.
Rats
given
lead
acetate
or
subacetate
orally
have
developed
gliomas,
and
lead
subacetate
also
produced
lung
adenomas
in
mice
after
i.
p.
administration.
Most
of
these
investigations
found
a
carcinogenic
response
only
at
the
highest
dose.
The
lead
compounds
tested
in
animals
are
almost
all
soluble
salts.
Metallic
lead,
lead
oxide
and
lead
tetraalkyls
have
not
been
tested
adequately.
Studies
of
inhalation
exposure
have
not
been
located
in
the
literature.

Azar
et
al.
(
1973)
administered
10,
50,
100,
and
500
ppm
lead
as
lead
acetate
in
dietary
concentrations
to
50
rats/
sex/
group
for
2
years.
Control
rats
(
100/
sex)
received
the
basal
laboratory
diet.
In
a
second
2­
year
feeding
study,
20
rats/
group
were
given
diets
containing
0,
1000,
and
2000
ppm
lead
as
lead
acetate.
No
renal
tumors
were
reported
in
the
control
groups
or
in
treated
animals
of
either
sex
receiving
10
to100
ppm.
Male
rats
fed
500,
1000,
and
2000
ppm
lead
acetate
had
an
increased
renal
tumor
incidence
of
5/
50,
10/
20,
and
16/
20,
while
7/
20
females
in
the
2000
ppm
group
developed
renal
tumors.

The
Azar
et
al.
(
1973)
study
is
limited
by
the
lack
of
experimental
detail.
The
possibility
of
environmental
contamination
from
lead
in
the
air
or
drinking
water
was
not
mentioned.
The
strain
of
rats
used
was
not
specified
in
the
study,
but
the
Health
Effects
Assessment
for
Lead
(
U.
S.
EPA,
1984)
indicates
the
rats
were
Wistar
strain.
The
weight
gain
at
1000
and
2000
ppm
was
reported
to
be
depressed,
but
details
were
not
given.

Kasprzak
et
al.
(
1985),
in
investigating
the
interaction
of
dietary
calcium
on
lead
carcinogenicity,
fed
1%
lead
subacetate
(
8500
ppm
Pb)
to
male
Sprague­
Dawley
rats
in
the
diet
for
79
weeks.
Of
the
rats
surviving
(
29/
30)
in
this
treatment
group
beyond
58
weeks,
44.8%
had
renal
tumors.
Four
rats
had
adenocarcinomas;
the
remaining
nine
had
adenomas.
Bilateral
tumors
were
noted.
No
renal
tumors
were
noted
among
the
controls.

As
part
of
a
study
to
determine
interactions
between
sodium
nitrite,
ethyl
urea
and
lead,
male
Sprague­
Dawley
rats
were
given
lead
acetate
in
their
drinking
water
for
76
weeks
(
Koller
et
al.,
1986).
The
concentration
of
lead
was
2600
ppm.
No
kidney
tumors
were
detected
among
the
10
control
rats.
Thirteen
of
16
(
81%)
lead­
treated
rats
had
renal
tubular
carcinoma;
three
tumors
were
detected
at
72
weeks
and
the
remainder
detected
at
the
termination
of
the
study.

Van
Esch
and
Kroes
(
1969)
fed
basic
lead
acetate
at
0,
0.1%,
and
1.0%
in
the
diet
to
25
Swiss
mice/
sex/
group
for
2
years.
No
renal
tumors
developed
in
the
control
group,
but
6/
25
male
mice
of
0.1%
basic
lead
acetate
group
had
renal
tumors
(
adenomas
and
carcinomas
combined).
In
the
1.0%
group,
one
female
had
a
renal
tumor.
The
authors
thought
that
the
low
incidence
in
the
1.0%
group
was
due
to
early
mortality.

Hamsters
given
lead
subacetate
at
0.5%
and
1%
in
the
diet
had
no
significant
renal
tumor
response
(
Van
Esch
and
Kroes,
1969).

__
II.
A.
4.
Supporting
Data
for
Carcinogenicity
Lead
acetate
induces
cell
transformation
in
Syrian
hamster
embryo
cells
(
DiPaolo
et
al.,
1978)
and
also
enhances
the
incidence
of
simian
adenovirus
induction.
Lead
oxide
showed
similar
enhanced
adenovirus
induction
(
Casto
et
al.,
1979).

Under
certain
conditions
lead
compounds
are
capable
of
inducing
chromosomal
aberrations
in
vivo
and
in
tissue
cultures.
Grandjean
et
al.
(
1983)
showed
a
relationship
between
sister
chromatid
exchange
and
lead
exposure
in
exposed
workers.
Lead
has
been
shown,
in
a
number
of
DNA
structure
and
function
assays,
to
affect
the
molecular
processes
associated
with
the
regulation
of
gene
expression
(
U.
S.
EPA,
1986b).

Back
to
top
_
II.
B.
Quantitative
Estimate
of
Carcinogenic
Risk
from
Oral
Exposure
Not
available.

Quantifying
lead's
cancer
risk
involves
many
uncertainties,
some
of
which
may
be
unique
to
lead.
Age,
health,
nutritional
state,
body
burden,
and
exposure
duration
influence
the
absorption,
release,
and
excretion
of
lead.
In
addition,
current
knowledge
of
lead
pharmacokinetics
indicates
that
an
estimate
derived
by
standard
procedures
would
not
truly
describe
the
potential
risk.
Thus,
the
Carcinogen
Assessment
Group
recommends
that
a
numerical
estimate
not
be
used.

Back
to
top
_
II.
C.
Quantitative
Estimate
of
Carcinogenic
Risk
from
Inhalation
Exposure
Not
available.

Back
to
top
_
II.
D.
EPA
Documentation,
Review,
and
Contacts
(
Carcinogenicity
Assessment)

__
II.
D.
1.
EPA
Documentation
Source
Document
­­
U.
S.
EPA,
1984,
1986,
1989
U.
S.
EPA,
1989
has
received
OHEA
and
SAB
review.

The
1986
Air
Quality
Criteria
Document
for
Lead
has
received
Agency
and
External
Review.

__
II.
D.
2.
EPA
Review
(
Carcinogenicity
Assessment)

Verification
Date
­­
05/
04/
1988
Screening­
Level
Literature
Review
Findings
­­
A
screening­
level
review
of
the
more
recent
toxicology
literature
pertinent
to
the
cancer
assessment
for
Lead
and
compounds
(
inorganic),
conducted
by
an
EPA
contractor
in
September
2002,
did
not
identify
any
critical
new
studies.
IRIS
users
who
know
of
important
new
studies
may
provide
that
information
to
the
IRIS
Hotline
at
hotline.
iris@
epa.
gov
or
(
202)
566­
1676.

__
II.
D.
3.
EPA
Contacts
(
Carcinogenicity
Assessment
Please
contact
the
IRIS
Hotline
for
all
questions
concerning
this
assessment
or
IRIS,
in
general,
at
(
202)
566­
1676
(
phone),
(
202)
566­
1749
(
fax),
or
hotline.
iris@
epa.
gov
(
email
address).

Back
to
top
_
III.
[
reserved]
_
IV.
[
reserved]
_
V.
[
reserved]

_
VI.
Bibliography
Substance
Name
­­
Lead
and
compounds
(
inorganic)
CASRN
­­
7439­
92­
1
Section
V.
I.
Last
Revised
­­
07/
08/
2004
_
VI.
A.
Oral
RfD
References
None.

Back
to
top
_
VI.
B.
Inhalation
RfC
References
None.

Back
to
top
_
VI.
C.
Carcinogenicity
Assessment
References
Anderson,
E.
L.,
and
CAG
(
Carcinogenic
Assessment
Group).
1983.
Quantitative
approaches
in
use
to
assess
cancer
risk.
Risk
Analysis.
3:
277­
295.

Azar,
A.,
H.
J.
Trochimowicz
and
M.
E.
Maxfield.
1973.
Review
of
lead
studies
in
animals
carried
out
at
Haskell
Laboratory
­
Two
year
feeding
study
and
response
to
hemorrhage
study.
In:
Barth
D.,
A.
Berlin,
R.
Engel,
P.
Recht
and
J.
Smeets,
Ed.
Environmental
health
aspects
of
lead:
Proceedings
International
Symposium;
October
1972;
Amsterdam,
The
Netherlands.
Commission
of
the
European
Communities,
Luxemberg.
p.
199­
208.

Casto,
B.
C.,
J.
Meyers
and
J.
A.
DiPaolo.
1979.
Enhancement
of
viral
transformation
for
evaluation
of
the
carcinogenic
or
mutagenic
potential
of
inorganic
metal
salts.
Cancer
Res.
39:
193­
198.

Cooper,
W.
C.
1985.
Mortality
among
employees
of
lead
battery
plants
and
lead
producing
plants,
1947­
1980.
Scand.
J.
Work
Environ.
Health.
11:
331­
345.

Cooper,
W.
C.
and
W.
R.
Gaffey.
1975.
Mortality
of
lead
workers.
In:
Proceedings
of
the
1974
Conference
on
Standards
of
Occupational
Lead
Exposure,
J.
F.
Cole,
Ed.,
February,
1974.
Washington,
DC.
J.
Occup.
Med.
17:
100­
107.

Dingwall­
Fordyce,
I.
and
R.
E.
Lane.
1963.
A
follow­
up
study
of
lead
workers.
Br.
J.
Ind.
Med.
20:
313­
315.

DiPaolo,
J.
A.,
R.
L.
Nelson
and
B.
C.
Casto.
1978.
In
vitro
neoplastic
transformation
of
Syrian
hamster
cells
by
lead
acetate
and
its
relevance
to
environmental
carcinogenesis.
Br.
J.
Cancer.
38:
452­
455.

Grandjean,
P.,
H.
C.
Wulf
and
E.
Niebuhr.
1983.
Sister
chromatid
exchange
in
response
to
variations
in
occupational
lead
exposure.
Environ.
Res.
32:
199­
204.

Kasprzak,
K.
S.,
K.
L.
Hoover
and
L.
A.
Poirier.
1985.
Effects
of
dietary
calcium
acetate
on
lead
subacetate
carcinogenicity
in
kidneys
of
male
Sprague­
Dawley
rats.
Carcinogenesis.
6(
2):
279­
282.

Koller,
L.
D.,
N.
I.
Kerkvliet
and
J.
H.
Exon.
1986.
Neoplasia
induced
in
male
rats
fed
lead
acetate,
ethyl
urea
and
sodium
nitrate.
Toxicol.
Pathol.
13:
50­
57.

Nelson,
D.
J.,
L.
Kiremidjian­
Schumacher
and
G.
Stotzky.
1982.
Effects
of
cadmium,
lead,
and
zinc
on
macrophage­
mediated
cytotoxicity
toward
tumor
cells.
Environ.
Res.
28:
154­
163.

Selevan,
S.
G.,
P.
J.
Landrigan,
F.
B.
Stern
and
J.
H.
Jones.
1985.
Mortality
of
lead
smelter
workers.
Am.
J.
Epidemiol.
122:
673­
683.

U.
S.
EPA.
1984.
Health
Effects
Assessment
for
Lead.
Prepared
by
the
Office
of
Health
and
Environmental
Assessment,
Environmental
Criteria
and
Assessment
Office,
Cincinnati,
OH,
for
the
Office
of
Emergency
and
Remedial
Response,
Washington,
DC.
EPA/
540/
1­
86/
055.
NTIS
PB85­
163996/
AS.

U.
S.
EPA.
1986a.
Guidelines
for
Carcinogen
Risk
Assessment.
Environmental
Protection
Agency,
Washington,
DC.
51
FR
33992­
34003.

U.
S.
EPA.
1986b.
Air
Quality
Criteria
Document
for
Lead.
Volumes
III,
IV.
Prepared
by
the
Office
of
Health
and
Environmental
Assessment,
Environmental
Criteria
and
Assessment
Office,
Research
Triangle
Park,
NC,
for
the
Office
of
Air
Quality
Planning
and
Standards.
EPA­
600/
8­
83/
028dF.

U.
S.
EPA.
1989.
Evaluation
of
the
potential
carcinogenicity
of
lead
and
lead
compounds:
In
support
of
reportable
quantity
adjustments
pursuant
to
CERCLA
Section
102.
Prepared
by
the
Office
of
Health
and
Environmental
Assessment,
Washington,
DC.
EPA/
600/
8­
89/
045A.
(
External
Review
Draft).

Van
Esch,
G.
J.
and
R.
Kroes.
1969.
The
induction
of
renal
tumors
by
feeding
of
basic
lead
acetate
to
mice
and
hamsters.
Br.
J.
Cancer.
23:
265­
271.

Back
to
top
_
VII.
Revision
History
Substance
Name
­­
Lead
and
compounds
(
inorganic)
CASRN
­­
7439­
92­
1
File
First
On­
Line
03/
01/
1988
Date
Section
Description
09/
26/
1988
II.
Carcinogen
summary
on­
line
02/
01/
1989
IV.
B.
1.
Effect
level
corrected
in
discussion
06/
01/
1989
II.
D.
3.
Primary
contact
changed
06/
01/
1989
IV.
A.
1.
Reference
corrected
­
changed
number
for
part
in
CFR
12/
01/
1989
II.
A.
3.
Last
paragraph
­
Correct
Van
Esch
1969
citation
12/
01/
1989
VI.
Bibliography
on­
line
07/
01/
1990
I.
A.
Changed
contact
J.
Cohen's
office
and
telephone
number
07/
01/
1990
IV.
F.
1.
EPA
contact
changed
02/
01/
1991
I.
A.
Message
revised
to
include
new
EPA
document
02/
01/
1991
I.
A.
EPA
contacts
changed
05/
01/
1991
II.
A.
Text
edited
01/
01/
1992
IV.
Regulatory
actions
updated
06/
01/
1992
IV.
B.
2.
MCL
monitoring
reqs.
and
BAT
corrected
07/
01/
1993
II.
D.
3.
Secondary
contact's
phone
number
changed
07/
01/
1993
VI.
C.
References
alphabetized
correctly
11/
01/
1993
II.
D.
1.
U.
S.
EPA
1987
replaced
with
1989;
rev.
state.
revised
11/
01/
1993
VI.
C.
U.
S.
EPA
1987
deleted;
U.
S.
EPA
1989
added
04/
01/
1997
III.,
IV.,
V.
Drinking
Water
Health
Advisories,
EPA
Regulatory
Actions,
and
Supplementary
Data
were
removed
from
IRIS
on
or
before
April
1997.
IRIS
users
were
directed
to
the
appropriate
EPA
Program
Offices
for
this
information.
12/
03/
2002
I.
A.,
II.
D.
2.
Screening­
Level
Literature
Review
Findings
message
has
been
added.
07/
08/
2004
I.
A.,
I.
B.,
II.
Previous
reference
value
discussions
replaced
with
links
to
EPA
websites
containing
regulatory
information
and
other
websites
with
risk
assessment
information;
cancer
discussion
retained,
added
links
to
agencies
conducting
reviews
of
lead
carcinogenicity.

Back
to
top
_
VIII.
Synonyms
Substance
Name
­­
Lead
and
compounds
(
inorganic)
CASRN
­­
7439­
92­
1
Last
Revised
­­
07/
08/
2004
7439­
92­
1
Lead
Lead
and
compounds
plumbum
Back
to
top
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