540186055
United States
Environmental Protection
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
HEALTH EFFECTS ASSESSMENT
FOR LEAD
Do not remove. This document
should be retained in the EPA
Region 5 Library Collection.
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EPA/540/1-86-055
September 1984
HEALTH EFFECTS ASSESSMENT
FOR LEAD
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
U S Environmental Protection Agency
Kesion V, Library
230 South Dearborn Street .^
Chicago, Illinois 60604
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with lead. All
estimates of acceptable Intakes and carcinogenic potency presented 1n this
document should be considered as preliminary and reflect limited resources
allocated to this project. Pertinent toxlcologlc and environmental data
were located through on-line literature searches of the Chemical Abstracts,
TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases. The basic
literature searched supporting this document 1s current up to September,
1984. Secondary sources of Information have also been relied upon In the
preparation of this report and represent large-scale health assessment
efforts that entail extensive peer and Agency review. The following Office
of Health and Environmental Assessment (OHEA) sources have been extensively
utilized:
U.S. EPA. 1977. A1r Quality Criteria for Lead. U.S. EPA, ORD,
Washington, DC. EPA 600/8-77-017.
U.S. EPA. 1980b. Ambient Water Quality Criteria for Lead.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-057. NTIS PB 81-117681.
U.S. EPA. 1983a. Reportable Quantity for Lead (and compounds).
Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency
Response, Washington, DC.
U.S. EPA. 1984. A1r Quality Criteria for Lead. Environmental
Criteria and Assessment Office, Research Triangle Park, NC, OHEA.
EPA 600/8-83-028B. NTIS PB 85-163996.
The Intent In these assessments Is to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer Is not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, Is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants In ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, 1s similar 1n concept to the ADI
(acceptable dally Intake). It Is an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980a) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes 1s Insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development Is explained In U.S. EPA (1983b).
For compounds for which there 1s sufficient evidence of carclnogenlclty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer 1s a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation In proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Lead 1s an extremely well studied compound. Despite the Immense volume
of data, or perhaps because of H, there Is still uncertainty concerning
"safe" exposure levels. As methods become Increasingly sophisticated,
effects are detected at lower levels. An underlying premise of the current
air standard and ambient water quality criterion Is that children are the
most sensitive segment of the population and 1f blood lead levels 1n the
majority of children are maintained <30 pg/da, an adequate margin of
safety for adverse effects will be achieved. However, the target level of
30 vg/da 1s currently being reviewed. New guidelines may potentially be
developed.
Another major problem associated with lead exposure Is the ubiquitous
nature of the compound. Unlike most other contaminants where exposure may
be related to a specific route or situation, substantial "background" lead
exposure occurs, primarily through food. This background exposure must be
considered when guidelines for Individual media or exposure routes are
suggested.
The approach taken 1n the present document was to make use of the
current air standard (1.5 vg/m3) and Information In the water quality
criterion derivation (50 yg/8,) as the best available estimates at the
present time. For reasons discussed 1n the text, AIC values In units of
mg/day have not been estimated. A CS of 35 has been calculated for lead
based on reduced survival of offspring 1n mice treated by Inhalation.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was the Project
Officer. The final documents 1n this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
ENVIRONMENTAL CHEMISTRY AND FATE • ,
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . . .
2.1.
2.2.
ORAL
INHALATION ,
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS ,
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral ,
3.1.2. Inhalation ,
CHRONIC ,
3.2.1. Oral ,
3.2.2. Inhalation ,
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
Page
1
5
. . . 5
6
. . . 7
, . . 9
. . . 9
. . . 12
. . . 12
. . . 12
. . . 14
. . . 14
. . . 14
. . . 17
. . . 17
, , 19
. . . 19
, . . 19
. . . 19
. . . 19
, . . 19
, , 20
. . . 20
, . . 20
. . . 21
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 22
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 22
6.1.1. Oral 22
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 22
6.2.1. Oral 24
6.2.2. Inhalation 24
6.3. CARCINOGENIC POTENCY (q-)*) 25
7. REFERENCES 26
APPENDIX: Summary Table for Lead 43
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LIST OF TABLES
No. Title Page
1-1 Selected Physical Properties of a Few Lead Compounds 2
3-1 Summary of Lowest Blood Lead Levels Associated with
Observed Biological Effects 1n Various Population Groups. . . 10
3-2 Subchronlc Oral Toxldty of Lead In Experimental Animals. . . 11
3-3 Chronic Oral Toxldty of Lead 1n Experimental Animals .... 13
3-4 Summary of Blood Inhalation Slopes (B) 15
3-5 Statistics on the Effect of Lead on Pregnancy 18
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
ADP Adenoslne 5'-d1phosphate
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
ALA 6-am1nolevul1n1c add
ALAO 5-am1nolevul1n1c acid dehydrase
bw Body weight
CAS Chemical Abstract Service
CNS Central nervous system
CP Coproporphyrln
CS Composite score
FEP Forced expiratory pressure
GI ' Gastrointestinal
LOAEL Lowest-observed-adverse-effect level
LOEL Lowest-observed-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
PEL Permlssable exposure limit
RQ Reportable quantity
RV(j Dose-rating value
RVe Effect-rating value
STEL Short-term exposure limit
TLV Threshold limit value
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Lead 1s a metal in Group IVB of the periodic table. Elemental lead has
a CAS Registry number of 7439-92-1. The Inorganic chemistry of lead Is
dominated by compounds 1n the +2 valence state. The primary examples of
lead in the 0 valence state are metal and alloys and the +4 valence state 1s
dominated by organolead compounds. The most Important organolead compounds
are tetramethyl lead and tetraethyl lead. Selected physical properties of a
few environmentally significant lead compounds are given In Table 1-1.
The environmental fate of lead has been extensively reviewed by U.S. EPA
(1977) and Boggess and Wlxson (1977). In this report, the environmental
fate of lead will be discussed only briefly. In the atmosphere, lead is
present primarily as particulate matter from exhaust of Internal combustion
engines using leaded fuel, coal or fuel oil combustion, from lead mining and
refining operation and from welding of certain coated or uncoated steel
(U.S. EPA, 1977; NIOSH, 1972). Small amounts of organic lead vapors (mainly
tetramethyl lead vapors) have been reported 1n the vicinity of gasoline
stations, garages and heavy traffic areas (U.S. EPA, 1977). These organic
vapors are expected to undergo photodecomposHlon to form particulate
matter, or the vapor may remain adsorbed on dust particles in the air (U.S.
EPA, 1977).
Lead from different stationary and mobile sources is emitted as differ-
ent chemical species 1n the atmosphere. Vehicular exhausts produce primar-
ily emissions of PbBrCl (Boggess and Wlxson, 1977). Emission from coal or
fuel combustion consists primarily of PbO and PbSO.. Smelting, mining and
refining processes produce primarily PbS, PbSO. and elemental Pb (Boggess
and Wlxson, 1977); however, the major lead-containing atmospheric species
-1-
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TABLE 1-1
Selected Physical Properties of a Few Lead Compounds3
Element/
Compound
Lead
Lead
chloride
Lead
bromide
Lead
oxide
Lead
sulflde
Lead
sulfate
Lead
tetramethyl
Lead
tetraethyl
Formula
Pb
PbCl2
PbBr2
PbO
PbS
PbS04
Pb(CH3)4
Pb(C2H5)4
Atomic
Molecular/
Weight
207.19
278.10
367.01
223.19
239.19
303.25
267.33
323.44
Water Solubility
Insoluble
0.99 g/100 ma
at 20°C
0.844 g/100 ma
at 20°C
1.7xlO"3 g/100
mt at 20°C
8.6xlO~5 g/100
ma at 25°C
4.25xlO~3 g/100
ma at 25°C
15 mg/a (Pb)b
0.8 mg/a at 20°C
Vapor Pressure
1 mm at 973°C
1 mm at 547°C
1 mm at 513°C
1 mm at 943°C
1 mm at 852°C
NA
22.5 mm at 20°C
0.15 mm at 20°C
aSource: Weast, 1980; Verschueren, 1983
^Temperature not specified
NA = Not available
-2-
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are PbBrC1-NH4Cl, PbS04 and PbCOg (Boggess and Wlxson, 1977).
Although little 1s known about the atmospheric Interactions of lead species,
1t 1s obvious that some Intractlons must be responsible for the formation of
prevalent lead-containing species 1n the atmosphere.
Chemical reactions of lead species 1n the atmosphere may cause transfor-
mation of one species to another, but these reactions do not remove lead
from the atmosphere. Similarly, photochemical decomposition of tetramethyl
lead and tetraethyl lead (U.S. EPA, 1977) may convert these species Into the
elemental form that may subsequently be oxidized to PbSO. or PbCO,, 1n
the presence'of SO- and C0_ 1n the atmosphere. This process, however,
does not remove lead from the atmosphere. A more likely fate of atmospheric
lead alkyls 1s sorptlon onto the surface of atmospheric partlculates and
subsequent conversion Into Inorganic lead compounds (Boggess and Wlxson,
1977).
Lead 1s removed from the atmosphere through wet and- dry deposition.
Removal through rainfall (washout, the Incorporation of a particle Into
precipitation below the cloud base) probably Is Insignificant compared to
the ralnout process which occurs within a cloud (Boggess and Wlxson, 1977).
Therefore, both the dry deposition and In-cloud ralnout processes are prin-
cipally responsible for the removal of lead from the atmosphere.
The atmospheric residence time for lead before Its final removal through
ralnout and dry deposition 1s dependent predominantly on the particle size.
It Is estimated that 75% of the partlculate lead emitted from automobiles 1s
removed from the atmosphere In the Immediate vicinity of traffic sources.
Smaller particles from mobile sources and emission from tall stacks will
remain airborne longer and be transported over greater distances. Submlcron
(<1 ym diameter) particles may remain In the atmosphere for >1 week (U.S.
EPA, 1977).
-3-
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Lead 1n aquatic media is primarily removed to bed sediments by two pro-
cesses, precipitation as PbCCL, PbS, PbS04 or adsorption onto organic
materials, hydrous iron or manganese oxides. In some bodies of water, pre-
cipitation may be the most Important process, but under most circumstances
sorption may predominate. Biomethylation of lead by benthic microbes may
cause some remobilization of lead from bed sediments. It should be empha-
sized that the removal of lead from aquatic media may be strongly pH depen-
dent. In acidic pH ranges, lead may be more mobile than In alkaline pH
ranges because of Inherent higher solubility of predpHable lead salts and
lower sorption characteristics of lead 1n solution (Callahan et al., 1979).
Lead 1n soil 1s expected to undergo spedation to more Insoluble
PbSO., PbJPO.),, PbS and PbO salts (U.S. EPA, 1977). Lead does not
*r 0 H t
usually move downward in soil because of the relative Insolubility of lead
salts and the binding capacity of organic fractions that may be present in
soils (Boggess and Wixson, 1977). Under certain circumstances, however,
lead may be solubilized through complexatlon with organlcs present in soils
(U.S. EPA, 1977). In the absence of suitable sorbents, the complexed lead
may move downward in the soil. Page (1981) detected lead (1 yg/8. mean
concentration) 1n groundwater samples In New Jersey at a frequency of -100%.
Lead is bioconcentrated by aquatic organisms. The estimated bloconcen-
tration factor for lead in edible bivalve molluscs may vary from 17.5-2570,
whereas its value for edible fish may be -42-45 (U.S. EPA, 1980b).
-4-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
It has been estimated that, 1n man, -8% of the lead ingested dally 1s
absorbed (Kehoe, 1961a; Rablnowltz et al., 1974). Absorption of lead con-
sumed after a 6-hour fast was Increased up to 8-fold as compared with lead
consumed with food (Wetherlll et al., 1974). Garber and We1 (1974) observed
similar effects of dietary status 1n mice at a dose of 3 yg Pb/kg bw, but
not at much higher doses (2000 yg Pb/kg bw).
Age also has a major Influence on the extent of lead absorption from the
GI tract. Forbes and Relna (1974) and Kostlal et al. (1971) have observed
that GI absorption of lead 1n Infant rats was considerably greater than 1n
adults. Similar results have been observed 1n humans. Alexander et al.
(1973) and Zlegler et al. (1978) reported that -50% of the dietary lead was
absorbed by young children (3 months to 8.5 years old; majority <2 years
old).
Numerous dietary factors Influence the absorption of lead from the GI
tract. Lead absorption has been demonstrated to be enhanced by low dietary
Ca or Fe high dietary fat or low or high dietary protein (Sobel et al.,
1938; Six and Goyer, 1970, 1972; Barltrop and Khoo, 1975). Absorption 1s
decreased 1n animals receiving high mineral diets (Barltrop and Khoo,
1975). Zlegler et al. (1978) found an Inverse relationship between dietary
lead absorption and the Ca content of the diets of Infants.
The GI absorption of lead 1s also Influenced by the chemical nature of
the lead consumed. Barltrop and Meek (1975) Investigated the absorption of
a wide variety of lead compounds by mature rats. They found that lead
phthalate and lead carbonate were absorbed somewhat better than lead ace-
tate. Lead naphthenate, lead octoate and lead sulflde were absorbed -66% as
-5-
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well as lead acetate; 180-250 ym diameter elemental lead particles were
absorbed only 14% as well. Incorporation Into paint films results In up to
a 50% reduction In lead absorption (Gage and LHchfleld, 1969; Knelp et al.,
1974).
2.2. INHALATION
Randall et al. (1975) exposed four baboons to lead aerosols (P&304)
of varying particle size for 4 weeks. Absorption was faster for coarse
particles (1.6 urn) than for fine particles (0.8 ym). High lead levels
result 1n a reduction In the number of lung macrophages, resulting In pro-
longed residence times and Increased absorption (Blngham et al., 1968; Beck
et al., 1973; Bruch et al., 1973a,b). Pott and Brockhaus (1971) found that
large doses of Intratracheally administered lead bromide or lead oxide were
retained as completely as were Intravenous doses, but smaller doses were
retained to a significantly smaller extent.
Kehoe. (1961b,c,d) studied the deposition of combusted tetraethyl lead
(Pb9OJ 1n volunteers. Thirty-six percent of particles with an average
& w
diameter of 0.26 ym and 46% of the particles with an average diameter of
2.9 jim were deposited. Nozakl (1966) reported Inverse relationships
between respiration rate, particle size and lung deposition. Chamberlain et
al. (1975) reported a 35% deposition rate for lead from Inhaled automobile
exhaust at a respiration rate of !5/m1nute. For adult humans, the deposi-
tion rate of partlculate airborne lead Is -30-50%. It also appears that
essentially all of the lead deposited 1n the lower respiratory tract 1s
absorbed so that the overall absorption rate 1s 30-50% (U.S. EPA, 1984).
Respiratory uptake by children appears to be greater on a body weight basis.
One report has estimated that a 10-year-old child has a deposition rate
1.6- to 2.7-fold higher than the adult on a weight basis (U.S. EPA, 1984).
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
Considerable data exist on the effects of lead exposure In humans, but
these data are based on blood lead levels. In most cases, no estimate of
exposure or the contribution of various routes of exposure are available.
The available evidence suggests that effects of lead on the formation of
hemoglobin and other nemo-proteins are detectable at lower levels of lead
exposure than are effects on any other organ or system. The threshold for
decreased hemoglobin levels 1s -0.4 yg/ml blood 1n children {Betts et
al., 1973; Pueschel et al., 1972) and 0.5 yg/ma, blood In adults (Tola et
al., 1973). Altered biochemical parameters, as Indicated by Increased
urinary y-am1nolevu!1n1c add levels, are detectable at blood lead levels
of 0.4 yg/m«, In men and children and at somewhat lower levels In women
(Selander and Cramer, 1970; Haeger-Aronsen et al., 1974; NAS, 1972; Roels et
al., 1975).
Neurological effects In children appear to be another sensitive Indica-
tor of lead toxlclty. Subtle neurobehavloral effects that do not result 1n
clinical encephalopathy have been reported In children exposed to lead
levels. U.S. EPA (1984) has summarized the evidence for health effects at
low blood lead levels In non-overtly lead Intoxicated children as follows:
Among the most Important and controversial of these effects are
neuropsychologlcal and electrophyslologlcal effects evaluated as
being associated with low-level lead exposures In non-overtly lead
Intoxicated children. Indications of peripheral nerve dysfunction,
Indexed by slowed nerve conduction velocities (NCV), have been
shown In children down to blood lead levels as low as 30 yg/di.
As for CNS effects, none of the available studies on the subject,
Individually, can be said to prove conclusively that significant
cognitive (IQ) or behavioral effects occur In children at blood-Pb
levels <30 yg/dl. Rather, the collective neurobehavloral
studies of CNS cognitive (IQ) effects can probably now be most
reasonably Interpreted as being clearly Indicative of likely
associations between neuropsychologlc deficits and low-level lead
-7-
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exposures 1n young children resulting 1n blood-Pb levels ranging to
as low as 30-50 yg/dt. The magnitude of average observed IQ
deficits appears to be approximately 5 points at mean blood lead
levels of 50-70 yg/dj. and about 4 points at mean blood lead
levels of 30-50 yg/dl.
Certain additional recent studies have obtained results at
blood lead values mainly In the 15-30 yg/di range Interpreted
by some Investigators as being Indicative of small, but not
unimportant, effects of lead on cognitive functioning, the ability
to focus attention, appropriate social behavior, and other types of
behavioral performance. However, due to specific methodological
problems with each of these various studies, much caution 1s
warranted that precludes conclusive acceptance of the observed
effects being due to lead rather than other (at times uncontrolled
for) potentially confounding variables. This caution 1s particu-
larly warranted In view of other well-conducted studies now begin-
ning to appear 1n the literature which did not find statistically
significant associations between lead and similar effects at blood
lead levels below 30 yg/dl. Still, because such latter studies
found 1-2 point IQ deficits remaining after correction for con-
founding factors, lead cannot be totally ruled out as a possible
etlologlcal factor contributing to the Induction of such effects In
the 15-30 yg/dft. range, based on existing published studies.
Also of considerable Importance are studies which provide
evidence of changes 1n EEG brain wave patterns and CNs evoked
potential responses In non-overtly lead Intoxicated children. The
work of Burchflel et al. (1980) indicates significant associations
between IQ decrements, EEG pattern changes, and lead exposures
among children with average blood lead levels falling 1n a range of
30-50 yg/dit. Research results provided by Otto et al. (1981,
1982, 1983) also demonstrate clear, statistically significant
associations between electrophyslologlcal (SW voltage) changes and
blood-Pb levels 1n the range of 30-55 yg/dft. and analogous
associations at blood-Pb levels below 30 yg/dl (with no evident
threshold down to 15 yg/da. or somewhat lower). In this case,
the presence of electrophyslologlcal changes observed upon follow-
up of some of the same children 2 years and 5 years later suggests
persistence of such effects even 1n the face of later declines 1n
blood-Pb levels and, therefore, possible long-term persistence of
the observed electrophyslologlcal CNS changes. However, the
reported electrophyslologlcal effects 1n this case were not found
to be significantly associated with IQ decrements.
The precise medical or health significance of the neuropsycho-
loglcal and electrophyslologlcal effects found by the above studies
to be associated with low-level lead exposures 1s difficult to
state with confidence at this time. The IQ deficits and other
behavioral changes detected at blood lead levels above 30
yg/dft, although statistically significant, are generally rela-
tively small 1n magnitude as detected by the reviewed studies, but
nevertheless may still Impact the Intellectual development, school
-8-
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performance, and social development of the affected children suffi-
ciently so as to be regarded as adverse. This would be especially
true 1f such Impaired Intellectual development or school perform-
ance and disrupted social development were reflective of persist-
ing, long-term effects of low-level lead exposure In early child-
hood. The Issue of persistence of such lead effects, however,
remains to be more clearly resolved, with some study results
mentioned above suggesting relatively short-lived or markedly
decreasing lead effects on neuropsychologlcal functions over a few
years from early to later childhood and other studies suggesting
that significant low-level lead-Induced neurobehavloral and EE6
effects may, 1n fact, persist Into later childhood. At levels
below 30 jig/da, observed IQ and other neuropsychologlc effects
are typically of even smaller magnitude, lead's etlologlcal role 1n
producing them Is less clearly established, and their likely medi-
cal significant unclear (as 1s the case for electrophyslologlcal
changes observed at levels below 30
Threshold blood lead levels for various endpolnts In children and adults are
presented 1n Table 3-1.
3.1. SUBCHRONIC
3.1.1. Oral. The effects of subchronlc oral exposure of experimental
animals to lead are summarized In Table 3-2. Six reproduction studies were
located In which the effects of subchronlc oral exposures could be evalu-
ated. Three of these, Schroeder and MHchener (1971), Schroeder et al.
(1970) and Stowe and Goyer (1971) did not use doses sufficiently low enough
to establish a threshold for effects.
In one study described In three separate reports (Klmmel et al., 1980;
Grant et al., 1980; Fowler et al., 1980), groups of 60-90 21-day-old female
CD rats were administered a semlpurlf led, nutritionally adequate, virtually
lead-free diet. Lead acetate was administered 1n delonlzed drinking water
at concentrations of 0, 0.5, 5, 50 or 250 mg Pb/J. H20. The treated
females were mated with untreated males after 6-7 weeks and were continued
on treatment throughout gestation and lactation. The pups were continued on
the same treatment as the dams from weaning through 6-9 months of age.
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TABLE 3-1
Summary of Lowest Blood Lead Levels Associated with Observed
Biological Effects 1n Various Population Groups*
LOEL
Pb/100 ml
Blood)
Effect
Population Group
10
15-20
10-15
10-30
25-30
40
40
40-100
80-100
80
70
40-50
30-40
40
40
40
50
50-60
80-100
100-120
ALA-D Inhibition
erythrocyte protoporphyrln elevation
CNS electrophyslologlcal deficits
vitamin D metabolism Interference
erythrocyte protoporphyrln elevation
Increased urinary ALA excretion
reduced hemoglobin production
chronic nephropathy
chronic nephropathy
frank anemia
frank anemia
altered testlcular function
slowed nerve conduction
slowed nerve conduction
coproporphyrln elevation
cognitive (CNS) deficits
reduced hemoglobin production
peripheral neuropathies
encephalopathlc symptoms
encephalopathlc symptoms
children and adults
women and children
children
children
adult males
children and adults
children
adults
children
adults
children
adults
children
adults
adults and children
children
adults
adults and children
children
adults
*Source: U.S. EPA, 1984
-10-
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TABLE 3-2
Subchronlc Oral Toxlclty of Lead In Experimental Animals
Compound
Species/
Strain/Sex Dose
Duration of
Exposure Effects
Reference
Lead acetate rats/CD/NF
0. 0.5. 5. 50
or 250 mg Pb/l
H20
Unspecified rats/NR/Mf
soluble salt mlce/NR/HF
Lead acetate rats/Sprague-
Dawley/HF
25 mg/l H20
10 g/kg diet
6-7 weeks pre-
breedlng until
609 months post-
partum
3 generations
2 generations
Decreased maternal body weight at 50 and
250 «g Pb/i. Delayed sexual maturation of
female offspring at 50 and 250 mg Pb/l and
to a smaller extent at 25 mg Pb/l. No
teratogenlc. fetotoxlc or reproductive effects
were observed. Delayed reflex maturation at
50 and 250 mg Pb/t. Delayed locomotor devel-
opment at 250 mg Pb/l. Dose-related Incidences
of poor fur condition, tall-tip necrosis and
slalodacryoadenltls. Hlstologlcal changes In
the kidneys at >5 mg/l.
Delayed birth. Hunting and excessive mortality
among offspring before weaning. Decrease In
male/female ratio. Decrease In number of
pregnancies and litter sizes. The effects
were more pronounced In mice than In rats.
Decreased pup weights. Decreased pups/litter.
Klmmel et al.. 1980.
Grant et al.. 1980;
Fowler et al.. 1980
Schroeder and
Kitchener 1971;
Schroeder
et al.. 1970
Stowe and Goyer.
1971
NR = Not reported
-------
There were no treatment-related differences In food or water consumption
between the various treatment groups; however, body weights were depressed
at the two highest doses. Sexual maturation, as measured by the time of
vaginal opening, was delayed 1n a dose-dependent manner, with effects
observed at a concentration >25 mg Pb/8.. No fetotoxlc, teratogenlc or
reproductive effects were noted, although the mean body length of the female
pups at 1 day of age was significantly decreased In the high dose groups.
The most sensitive Indication of lead toxlclty In the offspring was hlsto-
loglcal changes In the kidney. Cytokaryomegaly of the tubular epithelial
cells of the Inner cortex was observed In males at concentrations as low as
5 mg/a, and 1n both sexes at water concentrations of >25 mg/a. Assuming
that rats consume 35 mi of water each day and weigh 0.35 kg, the LOAEL of
5 mg/a corresponds to a dose of 0.5 mg/kg bw/day.
No effects were reported 1n humans which could be unequivocally attri-
buted to subchronlc exposures.
3.1.2. Inhalation. Data regarding the effects of subchronlc 1'nhalatlon
exposure to lead could not be located 1n the available literature.
3.2. CHRONIC
3.2.1. Oral. The chronic oral toxldty of lead 1n experimental animals
1s summarized 1n Table 3-3. Kopp et al. (1980a,b) reported that administra-
tion of lead acetate (5 mg Pb/a H_0) to female Long-Evans rats for 20
months produced slight effects on conduction tissue excitability, systolic
blood pressure and cardiac ATP concentrations. This represents the lowest
concentration at which chronic exposure to lead In the drinking water or
diet has been demonstrated to produce adverse effects. Assuming that rats
consume 35 ml of water each day and weigh 0.35 kg, this corresponds to a
dose of 0.5 mg/kg bw/day.
-12-
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TABLE 3-3
Chronic Oral Toxlctty of Lead In Experimental Animals
Compound
Species/Strain/Sex
Dose
Duration of
Exposure
Effects
Reference
Lead nitrate
NR
Lead acetate
rats/Long-Evans/
male
rats/NR/NR
rats/Long-Evans/
female
u
i
Lead arsenate rats/NR/NF
Lead carbonate
Calcium
arsenate
Lead arsenate
rats/Wlstar/NF
25 mg Pb/l h^O lifetime Decreased fasting blood glucose levels.
Increased Incidence of glycosurea, weight
loss and poor hair coats
25 mg Pb/l H?0 lifetime Same as above, except diet not supplemented
with chromium, decreased survival and longevity.
5 mg Pb/l HpO 20 months Slight -depression of conduction tissue excit-
ability, sporadic slight Increases In systolic
blood pressure, decreased cardiac ATP concen-
trations and ATP/ADP ratios
597 mg PB/kg 2 years The authors concluded that some of the effects
diet of lead arsenate on the kidney were attributable
to the lead moiety, and hemoslderln deposition In
the spleen was due to the arsenate moiety. Lead
arsenate was slightly more toxic than lead
carbonate but slightly less toxic than calcium
arsenate.
0. 276 or 1104 29 months Decreased food consumption and body weight In
mg Pb/kg diet high-dose group, decreased blood hemoglobin
concentration and packed cell volumes In high
dose males; enlargement of bile duct with
dilatation and abscesses, marked bile-duct
proliferation, perlcholangltls, cholanglo-
Mbrosls and Intranuclear eoslnophlllc
Inclusions In the kidneys; no effects In the
low dose group
Schroeder et al.,
1970
Schroeder et al.,
1965
Kopp et al.,
1980a.b
Falrhall and Killer,
1941
Kroes et al.. 1974
NR = Not reported
-------
U.S. EPA (1984) has reviewed the literature relating blood lead levels
to lead exposure from food, water and dust/soil. They concluded that for
adults, the best slope estimate for dietary Intake In adults 1s 0.02
yg/da per yg Ingested. For children, the best slope estimate Is
higher, 0.16 yg/da per yg Ingested. For water, a slope estimate of
0.06 yg/da per yg/a 1s suggested. This estimate applies to water
levels <100 yg/a. In children, the Increment of Increase 1n lead levels
1n blood resulting from lead In dust and soil was estimated as 0.6-6.8
yg/da per 1000 yg/g lead 1n dust.
3.2.2. Inhalation. Pertinent data regarding the chronic Inhalation
toxldty of lead In experimental animals could not be located In the avail-
able literature. From the many available studies addressing the relation-
ship between lead Inhalation exposure and blood lead levels, U.S. EPA (1984)
has Identified those most relevant to ambient exposures. These studies are
shown In Table 3-4 which 1s adapted from U.S. EPA (1984). The median slope
from the three population studies evaluating children Is 1.92 yg/da/
yg/m3. U.S. EPA (1984) points out that the slope 1s not linear, but
Increases more rapidly In the upper range of air lead concentrations and
that the slope estimate at lower air lead concentrations may not wholly
reflect uncertainty about the shape of the curve at higher concentrations.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlc effect of orally
administered lead could be located In the available literature; however,
postnatal developmental delays have been reported In pups from rats that
received 50-250 mg lead/a drinking water throughout gestation {Klmmel et
al., 1976; Relter et a!., 1975). Other Investigators reported decreased
fertility and fetotoxlc effects 1n a variety of species following higher
-14-
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TABLE 3-4
Summary of Blood Inhalation Slopes (8)
per ug/ma)
Population Study Type
Children population
population
population
i
in
i
Adult male population
experiment
experiment
experiment
N
1074
148
879
149
43
6
5
Slope
1.92
2.46
1.52
1.32
1.75
1.25
2.14
Model Sensitivity8
of Slope
O.40-4.40)b'c»d
(1.55-2.46)b»c
n.07-1.52)b'c'd
(1.08-1.59)c*d
(1.52-3.38)e
(1.25-1.55)b
(2.14-3.51)f
Study
Angle and Hclntlre,
1979
Roels et al., 1980
Yankel et al.. 1977;
Walter et al.. 1980
Azar et al., 1975
Griffin et al.. 1975
Gross, 1979
Rablnowltz et al.,
1973, 1976, 1977
aSelected from among the most plausible statistically equivalent models; for nonlinear models, slope at
1.0 ng/ma
"Sensitive to choice of other correlated predictors such as dust and soil lead
cSens1t1ve to linear vs. nonlinear at low air lead
^Sensitive to age as a covaHate
eSens1t1ve to baseline changes In controls
^Sensitive to assumed air lead exposure
-------
oral doses of lead (Hllderbrand et al., 1973; Vermande van-Eck and Melgs,
1960; Hubermont et al., 1976; Malsin et al., 1975; Jacquet et al., 1975;
Cole and Bachhuber, 1914; Weller, 1915; Oer et al., 1976; Verma et al.,
1974). Schroeder et al. (1970) reported a reduction 1n the number of off-
spring from rats and mice exposed to 25 mg Pb/8, drinking water, but only
In animals receiving a chromium deficient diet.
Schroeder and MHchener (1971) obtained marked effects on reproductive
parameters 1n rats and mice 1n a 3-generat1on study with 25 ppm lead (from
an unspecified soluble lead salt) In the drinking water. The sem1-pur1f led
diet used was restricted In Its content of trace metals (particularly chrom-
ium), and the animals environment was designed to minimize exposure to trace
metals; these conditions may have contributed to the toxldty of lead
(Schroeder et al., 1970). Rats and mice of both sexes (five palrs/spedes)
were given 25 ppm lead In their drinking water from weaning and were allowed
to produce Utters through 6 months (mice) or 9 months (rats) of age. .Pairs
were selected randomly from F, Utters and were allowed to produce an Fp
generation, and a similar procedure was followed for the production of an
F_ generation. F, and F5 pairs were continued on the same treatments
O I c
as their parents had received. In rats, results of lead treatment Included
a delay 1n birth of the first Utter to the original parents, runting and
excessive mortality (p<0.05) among the offspring before weaning, a decrease
1n the male/female ratio of the F, generation, and a decrease In pregnan-
cies and Utter size by the third generation. In mice, the effects were
similar but more severe; by the second generation, the number of offspring
was Insufficient to continue the experiment.
-16-
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3.3.2. Inhalation. The only data available on the teratogenldty of
Inhaled lead are derived from ep1dem1olog1cal studies. In most cases,
reliable estimates of exposure are lacking. In high doses, lead compounds
have been used to Induce abortions (Tansslg, 1936). Oliver (1911) found
that the miscarriage rate was elevated among British women occupatlonally
exposed to lead (Table 3-5). Other Investigators have related lead expo-
sure, both before and during pregnancy, with Increases In spontaneous abor-
tions, premature delivery and early membrane rupture (Lane, 1949; Nozakl,
1958; Fahlm et al., 1975; Rom, 1976).
3.4. TOXICANT INTERACTIONS
A large number of dietary factors have been demonstrated to alter the GI
absorption, and thus presumably the toxldty, of orally administered lead
(see Section 2.1.). The Interrelationships between lead toxlclty and the
nutritional status of other metals 1s complex and has not been studied com-
pletely. High mineral diets Inhibit the absorption of lead (Barltrop and
Khoo, 1975) and diets low In calcium or Iron enhance absorption (Sobel et
al., 1938; Six and Goyer, 1970, 1972).
-17-
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TABLE 3-5
Statistics on the Effect of Lead on Pregnancy*
Sample
Number of
Abortions and
Stillbirths/
1000 Females
Number of
Neonatal Deaths
(first year)/
1000 Females
Housewives
Female workers (mill work)
Females exposed to lead premarltally
Females exposed to lead after marriage
43.2
47.6
86.0
133.5
150
214
157
271
*Source: Oliver, 1911
-18-
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Data pertinent to the oral carcinogenic potential of lead
to humans could not be located 1n the available literature.
4.1.2. Inhalation. The causes of death among people exposed to lead have
been Investigated In three ep1dem1olog1cal studies (Dlngwall-Fordyce and
Lane, 1963; Nelson et al., 1973; Cooper and Gaffey, 1975; Cooper, 1976,
1978). No association between lead exposure and cancer mortality was found
1n the two earlier studies, but In the study by Cooper and Gaffey (1975), a
statistically significant elevation 1n deaths due to "all malignant neo-
plasms" and cancer of "other sites" was reported. Using different statisti-
cal tests, Kang et al. (1980) reanalyzed these data and calculated a statis-
tically significant Increase 1n deaths due to cancer of the digestive organs
and cancer of the respiratory system for both lead smelter workers and
battery plant workers. Deaths due to all malignant neoplasms were Increased
among lead smelter workers only.
4.2. BIOASSAYS
4.2.1. Oral. Several studies have associated specific lead salts with
tumor formation 1n experimental animals. Dietary lead acetate at concentra-
tions of 3-4 mg/day (Zawlrska and Medras, 1968, 1972), 500-2000 mg/kg diet
(Azar et al., 1973) or 1% 1n the diet (Boyland et al., 1962) have produced
renal tumors 1n Wlstar rats. Lead subacetate has produced renal carcinomas
or adenomas 1n Swiss mice (Van Esch and Kroes, 1969) and In several strains
of rats (Van Esch et al., 1962; Oyasu et al., 1970; Mao and Molnar, 1967;
Shakerin and Paloucek, 1965; ShakeMn et al., 1965; Mass et al., 1967; Ito
et al., 1971; Ito, 1973), but not 1n golden hamsters (Van Esch and Kroes,
1969). Gliomas were also observed In many of these studies.
-19-
-------
4.2.2. Inhalation. Data pertinent to the carclnogenldty of Inhaled lead
could not be located 1n the available literature.
4.3. OTHER RELEVANT DATA
Data pertinent to the mutagenlclty of lead could not be located 1n the
available literature.
4.4. WEIGHT OF EVIDENCE
IARC (1980, 1982) considered the evidence for carclnogenldty to humans
to be "Inadequate," the evidence for carclnogenldty to animals to be "suf-
ficient for some salts" and evidence for activity 1n short-term tests to be
"Inadequate." Since humans are not environmentally exposed to the lead
salts associated with tumors 1n animals, lead and lead compounds are most
appropriately classified as Group 3-Poss1ble Human Carcinogens, using the
criteria for weight of evidence proposed by the Carcinogen Assessment Group
of the U.S. EPA (Federal Register, 1984). Those lead salts for which suffi-
cient evidence of carclnogenldty 1n animals exists are most appropriately
classified 1n Group B2-Probable Human Carcinogens.
-20-
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5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1980) has established a TLV of 0.15 mg/m3 and a STEL of
0.45 mg/m3 for "Inorganic compounds, dust and fume, as Pb." Separate TLVs
were established for lead arsenate [0.15 mg/m3 as Pb3 (Aj-OJp] and
lead chromate (0.05 mg/m3 as Cr).
The Occupational Safety and Health Administration (Code of Federal
Regulations, 1981) has defined an "action level" of 30 yg/m3 and a PEL
of 50 yg/m3, averaged over an 8-hour period. For work periods of >8
hours, the maximum permissible limit 1s defined as 400 yg/m3 * hours
worked 1n the day.
The U.S. EPA (1980b) recommended an ambient water quality criterion for
lead of 50 yg/i. The ACGIH (1980) reported limits of 0.01 mg/m3
established by the USSR, 0.02 mg/m3 established by Hungary, 0.05 mg/m3
established by Czechoslovakia and Poland, 0.1 mg/m3 established by
Romania, Sweden and West Germany and 0.15 mg/m3 established by East
Germany, Finland and Yugoslavia.
-21-
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. No data regarding the effects of subchronlc oral exposure
of humans to lead were found In the available literature. One study In rats
was located which could be used for the derivation of an AIS (Klmmel et al.,
1980; Grant et al., 1980; Fowler et al., 1980). For the most sensitive
parameter measured In this study, hlstologlcal changes In the kidneys, the
LOAEL was 5 mg Pb/2 H20 and the NOAEL was 0.5 mg Pb/a H20. Assuming
that rats consume 35 ma of water each day weigh 0.35 kg, the corresponding
doses are 0.5 and 0.05 mg/kg bw/day. The LOAEL will be used as the basis of
the risk assessment. Applying uncertainty factors of 10 to convert from a
LOAEL to a NOAEL, 10 for Interspedes conversion and 10 to afford Increased
protection for more sensitive members of the population, results 1n an AIS
of 0.5 yg/kg bw/day or 35 yg/day for a 70 kg man. This value 1s lower
than estimates for chronic human exposure and therefore Is not judged to be
an appropriate estimate-.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
Lead Is a ubiquitous compound and, therefore, It would be Inappropriate
to suggest route specific exposure levels that do not reflect the contribu-
tion of other routes. Baseline exposures to lead In adults are primarily a
function of food Intake with food > water > dust > Inhaled air. Lead In the
diet 1s the result of atmospheric dust, lead solder from cans, metals used
In grinding, crushing and sieving, and lead 1n water (U.S. EPA, 1984). In
children, the greatest exposure occurs through food and dust. Consequently,
control of air lead levels as the primary contamination route for food
(except canned food) and surface dust would be a major factor In controlling
overall lead exposure levels.
-22-
-------
Previous estimates of acceptable lead exposure which were based on
target blood lead levels of 30 yg/da, are currently being reevaluated.
U.S. EPA (1984) presents a comprehensive and critical evaluation of 'recent
data which suggest effects, especially In children, at blood lead levels
below 30 yg/da. If this target blood lead level Is decreased, parallel
decreases will be required In guidelines and standards delineating maximum
lead levels 1n environmental media.
Until the uncertainty concerning target blood lead levels 1s resolved,
It 1s suggested that the current air standard be used as a guideline for
Inhalation exposure (1.5 yg/m3). Although the relationship between
Inhaled lead and blood lead has been established, 1t 1s suggested that
estimation of absorbed dose 1n mg/day based on this air level would be
Inappropriate as a result of the substantial contribution of atmospheric
lead to the food and dust exposure components.
In addition, 1t Is proposed that water levels (water being the second
major exposure category In adults) be targeted at the proposed criterion
level (50 mg/fc).
Development of AIC values would be Inappropriate since these values
Implicitly assume zero exposure by other routes. With many chemicals this
1s a reasonable assumption. In the case of lead, the general population Is
already accruing unavoidable background exposures through food, water and
dust. As a result of substantial background exposure levels and because of
uncertainty concerning "safe" exposure levels, any significant Increase
above present lead levels 1n air, water and soil represents a cause for
concern In terms of human health endpolnts.
-23-
-------
6.2.1. Oral. As discussed In Section 6.2., an oral AIC for lead 1s not
suggested at the present time. A criterion level for water of 50 yg/8,
1s suggested based on U.S. EPA (1980b). This level should be reevaluated
when a consensus 1s reached concerning target blood lead levels. This water
level, In conjunction with the current air standard should limit oral lead
Intake levels, assuming lead 1s not directly Introduced Into soils (as
opposed to atmospheric deposition) used for agriculture.
An RQ for the decreased survival of offspring of mice In a 3-generatlon
reproduction study treated with an unspecified soluble lead salt at 25 ppm
lead 1n the drinking water (Schroeder and Mltchener, 1971) was calculated.
The animal dose, 4.25 mg/kg/day, was calculated by assuming mice Ingest
water equivalent to 17% of their body weight/day. Multiplication of the
animal dose by the cube root of the ratio of the body weight of mice
(assumed: 0.03 kg) to that of humans (assumed: 70 kg) resulted In a human
MED of 0.32 mg/kg/day or 22.4 mg/day for a 70 kg man. This human MED cor-
responds to an RV. of 3.5. Decreased survival of offspring was assigned
an RV of 10. A CS of 35, calculated as the product of RV. and RV ,
v U C
resulted.
6.2.2. Inhalation. As discussed 1n Section 6.2., an Inhalation AIC 1s
not suggested at the present time. The current air standard of 1.5
yg/m3 1s suggested as a maximum air level to limit Inhalation, dietary
and dust exposures. This level Is currently being reviewed. The reader 1s
referred to U.S. EPA (1984) for a detailed discussion.
-24-
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6.3. CARCINOGENIC POTENCY (q.,*)
The potential role of lead In the etiology of human cancer 1s Impossible
to assess at this time. In their summary U.S. EPA (1984) states:
"...at relatively high concentrations, lead displays some carcino-
genic activity 1n experimental animals (e.g., the rat)...It Is hard
to draw clear conclusions concerning what role lead may play 1n the
Induction of human neoplasla. Ep1dem1olog1cal studies of lead-
exposed workers provide no definitive findings...Also, since lead
acetate can produce renal tumors In some experimental animals, 1t
may be prudent to assume that at least that lead compound may be
carcinogenic in humans."
This statement 1s qualified, however, by noting that lead has been observed
to Increase tumorlgenesls rates 1n animals only at relatively high concen-
trations, and therefore does not appear to be an extremely potent carcinogen.
Additional data are needed concerning the potential role of lead In
human cardnogenesls and available data need to be carefully assessed by an
expert group.
-25-
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7. REFERENCES
AC6IH (American Conference of Governmental Industrial Hyg1en1sts). 1980.
Documentation of the Threshold Limit Values, 4th ed. (Includes Supplemental
Documentation for 1981, 1982, 1983). Cincinnati, OH. p. 243-246.
Alexander, F.W., H.T. Delves and B.E. Clayton. 1973. The uptake and
excretion by children of lead and other contaminants. In: Aspects of Lead,
Proc. Int. Symp. Environ. Health Amsterdam, October 26, 1972. Comm. Eur.
Commun., Luxembourg, p. 319-327. (Cited In U.S. EPA, 1980b)
Angle, C.R. and M.S. Mclntlre. 1979. Environmental lead and children: The
Omaha study. J. Toxlcol. Environ. Health. 5: 855-870.
Azar, A., H.J. Trochlmowlcz and M.E. Maxfleld. 1973. Review of Lead
Studies 1n Animals Carried out at Haskell Laboratory — Two-year Feeding
Study and Response to Hemorrhage Study. In.: Aspects of Lead, Proc. Int.
Symp. Environ. Health, Amsterdam, October 2-6, 1972. Comm. Eur. Commun.,
Luxembourg, p. 199-210.
Azar, A., et al. 1975. An ep1dem1olog1cal approach to community air lead
exposure using personal air samplers. Environ. Qua!. Safe. Suppl. II: Lead.
p. 254. (Cited In U.S. EPA, 1980b)
Barltrop, D. and H.E. Khoo. 1975. The Influence of nutritional factors on
lead absorption. Postgrad. Med. J. 51: 795-800. (Cited 1n U.S. EPA, 1980b)
-26-
-------
Barltrop, D. and F. Meek. 1975. Absorption of different lead compounds.
Postgrad. Med. J. 51: 805-809. (Cited 1n U.S. EPA, 1980b)
Beck, E.G., N. Manojlovlc and A.B. Fisher. 1973. Die Zytotoxlzltat von
Ble1 (1n English). In: Proc. Int. Symp. Environ. Health, Aspects of Lead,
Amsterdam, October 2-6. Comm. Eur. Commtm., Luxembourg. (CHed In U.S.
EPA, 1977)
Betts, P.R., R. Astley and R.N. Ralne. 1973. Lead Intoxication In children
1n Birmingham. Br. Med. J. 1: 402-406. (CHed In U.S. EPA, 1980b)
Blngham, E., E.A. Pfltzer, W. Barkley and E.P. Radford. 1968. Alveolar
macrophages: Reduced number In rats after prolonged Inhalation of lead
sesquloxlde. Science. 162: 1297-1299. (CHed 1n U.S. EPA, 1977)
Boggess, W.R. and B.6. Wlxson. 1977. Lead In the Environment. Report
prepared for the National Science Foundation. Report No. NSF/RA-770214,
Washington, DC.
Boyland, E., C.E. Dukes, P.L. Grover and B.C.V. MHchley. 1962. The
Induction of renal tumors by feeding lead acetate to rats. Br. J. Cancer.
16: 283-288. (CHed 1n U.S. EPA, 1983c)
Bruch, J., A. Brockhaus and W. Dehnen. 1973a. Electron-mlckroskoplsche
Beobachtungen an Rattenlungen nach. Exposition m1t Partlkel Formlgem Blel.
In: Proc. Int. Symp. Environ. Health, Effects of Lead, Amsterdam, October
2-6, 1972. Comm. Eur. Commun., Luxembourg, p. 221-229. (CHed In U.S.
EPA, 1977)
-27-
-------
Bruch, J., A. Brockhaus and W. Dehnen. 1973b. Local effects of Inhaled
lead compounds on the lung. In: Recent Advances In the Assessment of the
Health Effects of Environmental Pollution, Proc. CEC-DPA-WHO Int. Symp.,
Paris, June 24-28, 1974. Comm. Eur. Commun., Luxembourg, p. 781-793.
BurchHel, J.L., F.H. Duffy, P.H. Bartels and H.L. Needleman. 1980. The
combined discriminating power of quantitative electroencephalography and
neuropsychologlc measures 1n evaluating central nervous system effects of
lead at low levels. In.: Low-level Lead Exposure: The Clinical Implications
of Current Research, H.L. Needleman, Ed. Raven Press, New York, NY.
p. 75-89. (Cited 1n U.S. EPA, 1984)
Callahan, M.A., M.W. SUmak, N.W. Gabel, et al. 1979. Water-Related
Environmental Fate of 129 Priority Pollutants, Vol. II. U.S. EPA, Office of
Water Planning and Standards, Office of Water and Waste Management, Washing-
ton, DC. EPA 440/4-79-029.
Chamberlain, A.C., W.S. Clough, M.3. Heard, D. Newton, A.N.B. Stoth and A.C.
Wells. 1975. Uptake of lead by Inhalation of motor exhaust. Proc. Roy.
Soc. London. B. 192: 77-110. (Cited 1n U.S. EPA, 1977)
Code of Federal Regulations. 1981. OSHA Safety and Health Standards.
Lead. 29 CFR 1910.10000.
Cole, L.J. and L.J. Bachhuber. 1914. Effects of lead on the germ cells of
the male rabbit and fowl as Indicated by their progeny. Proc. Soc. Exp.
B1ol. Med. 12: 24. (Cited 1n U.S. EPA, 1977)
-28-
-------
Cooper, W.C. 1976. Cancer mortality patterns In the lead industry. Ann.
NY. Acad. Sci. 271: 250. (Cited 1n U.S. EPA, 1980b)
Cooper, W.C. 1978. Mortality 1n workers 1n lead production facilities and
lead battery plants during the period 1971-1975. A report to the Int. Lead
Z1nc Research Organization, Inc. and Equitable Environmental Health under
Contract LH-157. (CUed 1n U.S. EPA, 1980b)
Cooper, W.C. and W.R. Gaffey. 1975. Mortality of lead workers. J. Occup.
Med. 17: 100-107. (Cited In U.S. EPA, 1980b)
Der, R., Z. Fahlm, M. Yousef and M. Fahim. 1976. Environmental Interaction
of lead and cadmium on reproduction and metabolism of male rats. Res. Comm.
Chem. Pathol. Pharmacol, 14: 689-713. (Cited 1n U.S. EPA, 1977)
Olngwall-Fordyce, I. and R.E. Lane. 1963. A follow-up study of lead
workers. Br. 3. Ind. Med. 30: 313-315. (Cited 1n U.S. EPA, 1980b)
Fahlm, M.S., Z. Fahlm and D.6. Hall. 1975. Effects of subtoxlc lead levels
on pregnant women 1n the state of Missouri. Int. Conf. on Heavy Metals In
the Environment. Toronto, Ontario. October 27-31. (Cited 1n U.S. EPA,
1977)
Falrhall, L.T. and J.W. MUler. 1941. A study of the relative toxldty of
the molecular components of lead arsenate. Publ. Health Rep., Washington,
DC. 56: 1610-1625. (Cited In U.S. EPA, 1977; IARC, 1980)
-29-
-------
Federal Register. 1984. Environmental Protection Agency. Proposed Guide-
lines for Carcinogenic Risk Assessment. 49FR46294-46299.
Forbes, G.B. and J.C. Relna. 1974. Effect of age on gastrointestinal
absorption (Fe, Sr, Pb) 1n the rat. J. Nutr. 102: 647-652. (Cited In U.S.
EPA, 1980b)
Fowler, B.A., C.A. Klmmel, J.S. Woods, E.E. McConnell and L.D. Grant. 1980.
Chronic low-level lead toxldty 1n the rat. III. An Integrated assessment
of long-term toxldty with special reference to the kidney. Toxlcol. Appl.
Pharmacol. 56: 59-77. (Cited 1n U.S. EPA, 1984; IARC, 1980)
Gage, J.C. and M.H. LHchfleld. 1969. The migration of lead from paint
films In the rat gastrointestinal tract. J. 011. Col. Chem. Assoc. 52:
236-243. (Cited 1n U.S. EPA, 1980b)
Garber, B.T. and E. Wei. 1974. Influence of dietary factors on the gastro-
intestinal absorption of lead. Toxlcol. Appl. Pharmacol. 27: 685-691.
(Cited 1n U.S. EPA, 1980b)
Grant, L.D., C.A. Klmmel, G.L. West, C.M. Martinez-Vargas and J.L. Howard.
1980. Chronic low-level lead toxlclty 1n the rat. II. Effects on postnatal
physical and behavioral development. Toxlcol. Appl. Pharmacol. 56: 42-58.
(Cited In U.S. EPA, 1984)
-30-
-------
Griffin, T.B., F. Coulston, H. Willis, J.C. Russell and J.H. Knelson. 1975.
Clinical studies of men continuously exposed to airborne partlculate lead.
In: Lead, T.B. Griffin and J.H. Knelson, Ed. Academic Press, New York, NY.
p. 221-240.
Gross, S.B. 1979. Oral and Inhalation lead exposures 1n human studies
(Kehoe balance experiments). Lead Industries Assoc., New York, NY.
Haeger-Aronsen, B., M. Abdulla and B.I. FMstedt. 1974. Effect of lead on
gamma-am1nolevul1n1c acid dehydratase activity 1n red blood cells. I.
Regeneration of enzyme after cessation of lead exposure. Arch. Environ.
Health. 29: 150-153. (CHed In U.S. EPA, 1980b)
Hass, G.M., J.H. McDonald, R. Oyasu, H.A. Battlfora and J.T. Paloucek.
1967. Renal neoplasla Induced by combinations of dietary lead subacetate
and N-2-fluorenylacetam1de. |n.: Renal Neoplasla, J.S. King, Jr., Ed.
Little-Brown Company, Boston, MA. p. 377-412. (CHed 1n IARC, 1980)
HUderbrand, D., R. Der, W. Griffin and M. Fahlm. 1973. Effect of lead
acetate on reproduction. Am. J. Obst. Gynec. 155: 1058-1065. (CHed 1n
U.S. EPA, 1977)
Hubermont, G., J.P. Buchet, H.A. Roels and R.R. Lauwerys. 1976. Effect of
short-term administration of lead to pregnant rats. Toxlcolology. 5: 379.
(CHed 1n U.S. EPA, 1977)
-31-
-------
IARC (International Agency for Research on Cancer). 1980. Lead and Lead
Compounds. Ijn: Some Metals and Metallic Compounds. IARC Monographs on the
Evaluation of the Carcinogen Risk of Chemicals to Humans. WHO, IARC, Lyon,
France. Vol. 23, p. 325-415.
IARC (International Agency for Research on Cancer). 1982. Results and
conclusions. In.: Chemicals, Industrial Processes and Industries Associated
with Cancer 1n Humans. IARC Monographs on the Evaluation of the Carcino-
genic Risk of Chemicals to Humans. WHO, IARC, Lyon, France. Vol. 1-29
(Suppl 4).
Ito, N. 1973. Experimental studies on tumors of the urinary system of rats
Induced by chemical carcinogens. Acta Pathol. (Jap.) 23: 87-109. (Cited
In IARC, 1980)
Ito, N., Y. H1asa, Y. Kamamoto, et al. 1971. H1stopatholog1cal analysis of
kidney tumors 1n rats Induced by chemical carcinogens. Gann. 62: 435-444.
(Cited In IARC, 1980)
Jacquet, P., A. Leonard and G.B. Gerber. 1975. Progress report on studies
Into the toxic action of lead 1n biochemistry of the developing brain and on
cytogenetlcs of post melotlc germ cells. Economic Community of Europe,
Contract No. 037-038/74-7. Env. B. Brussels, Belgium: ECE. (Cited In U.S.
EPA, 1977)
Kang, H.K., et al. 1980. Occupational lead exposure and cancer. Letter to
the editor. Science. 207: 935. (Cited 1n U.S. EPA, 1980b)
-32-
-------
' ' Kehoe, R.A. 1961a. The Harben Lectures, 1960. The metabolism of lead In
man In health and disease. J. Roy. Inst. Pub. Health Hyg. 34: 1-81.
(Cited In U.S. EPA, 1980b)
Kehoe, R.A. 1961b. The metabolism of lead 1n man 1n health and disease.
I. The normal metabolism of lead. R. Inst. Public Health Hyg. 3. 24:
81-97. (Cited 1n U.S. EPA, 1977)
Kehoe, R.A. 1961c. The metabolism of lead 1n man 1n health and disease.
II. The metabolism of lead under abnormal conditions. R. Inst. Public
Health Hyg. J. 24: 129-143. (Cited 1n U.S. EPA, 1977}
Kehoe, R.A. 1961d. The metabolism of lead 1n man 1n health and disease.
III. Present hygienic problems relating to the absorption of lead. R. Inst.
Public Health Hyg. J. 24: 177-203. (Cited In U.S. EPA, 1977)
Klmmel, C.A., L.D. Grant and C.S. Sloan. 1976. Chronic lead exposure:
Assessment of development toxlclty. Teratology. 13: 27A. (CHed In U.S.
EPA, 1977)
Klmmel, C.A., L.D. Grant, C.S. Sloan and B.C. Gladen. 1980. Chronic
lowlevel lead toxlclty 1n the rat. I. Maternal toxldty and perinatal
effects. Toxlcol. Appl. Pharmacol. 56: 28-41. (CHed In U.S. EPA, 1984)
-33-
-------
Knelp, T.J.. D.H. Goldstein and N. Cohen. 1974. Lead toxlclty studies In
Infant baboons: A toxlcologlcal modes for childhood lead poisoning. Insti-
tute of Environmental Medicine; New York University Medical Center. Final
report to the Consumer Product Safety Commission, Contract CPSC-C-74-153.
(Cited In U.S. EPA, 1980b)
Kopp, S.J., T. Glonek, M. Erlanger, E.F. Perry, M. Barany and H.M. Perry,
Jr. 1980a. Altered metabolism and function of rat heart following chronic
low level cadmium/lead feeding. J. Mol. Cell. Cardlol. 12: 1407-1425.
(Cited 1n U.S. EPA, 1984)
Kopp, S.J., H.M. Perry, Jr., T. Glonek, et al. 1980b. Cardiac physiologic-
metabolic changes after chronic low-level heavy metal feeding. Am. J.
Physlol. 239: H22-H30. (Cited In U.S. EPA, 1984}
Kostlal, K., I. Slmonovlc anc M. P1son1c. 1971. Lead absorption from the
Intestine In newborn rats. Nature. 233: 564. (Cited In U.S. EPA, 1980b)
Kroes, R., M.J. Van Logten, J.M. Berkvlns, I. deVrles and G.J. van Esch.
1974. Study on the carclnogenldty of lead arsenate and sodium arsenate and
on the possible synerglstlc effect of d1ethyln1trosam1ne. Food Cosmet.
Toxlcol. 12: 671-679. (Cited 1n U.S. EPA, 1984)
Lane, R.E. 1949. The care of the lead worker. Br. J. Ind. Med. 6:
125-143. (Cited 1n U.S. EPA, 1977)
-34-
-------
' ' Malsln, J.R., J.M. Jade, M. Lamb1et-Coll1er. 1975. Progress report on
morphological studies of the toxic effects of lead on the reproductive
organs and the embryos. Economic Community of Europe Contract No. 080-74-7.
Env. B. Brussels, Belgium: ECE. (Cited In U.S. EPA, 1977)
Mao, P. and J.J. Molnar. 1967. The fine structure and hlstochemlstry of
lead-Induced renal tumors In rats. Am. J. Pathol. 50: 571-581. (Cited 1n
U.S. EPA, 1980b)
NAS (National Academy of Sciences). 1972. Airborne lead 1n perspective.
Washington, DC. (Cited In U.S. EPA, 1980b)
Nelson, W.C., M.H. Lyklns, 3. Mackey, V.A. Newlll, J.F. Flnklea and D.I.
Hammer. 1973. Mortality among orchard workers reposed to lead arsenate
spray: A cohort study. J. Chron. DIs. 26: 105-118. (Cited 1n U.S. EPA,
1980b)
NIOSH (National Institute for Occupational Safety and Health). 1972.
Criteria for a Recommended Standard.. .Occupational Exposure to Inorganic
Lead. U.S. DHEW, PHS, CDC, Rockvllle, MD. NTIS PB-214265.
Nozakl, K. 1958. On action of lead on body of lead refinery workers:
Particularly conception, pregnancy and parturition 1n case of females and
their newborn. Excerp. Med. XVII. 4: 2176. (Cited 1n U.S. EPA, 1977)
Nozakl, K. 1966. Method for studies on Inhaled particles In human respira-
tory system and retention of lead fume. Ind. Health. (Jap.) 4: 118-128.
(Cited In U.S. EPA, 1977)
-35-
-------
Oliver, T. 1911. Lead poisoning and the race. Br. Med. J. 1: 1096-1098.
(Cited In U.S. EPA, 1977)
Otto, 0., V. Benlgnus, K.E. Muller, et al. 1982. Effects of low to
moderate lead exposure on slow cortical potentials 1n young children: Two
year follow-up study. Neurobehav. Toxlcol. Teratol. 4: 733-737.
Oyasu, R., H.A. Battlfora, R.A. Clasen, J.H. McDonald and 6.M. Hass. 1970.
Induction of cerebral gllomas 1n rats with dietary lead subacetate and
2-acetylam1nofluorene. Cancer Res. 30: 1248-1261. (Cited 1n U.S. EPA,
1980b)
Page, G.W. 1981. Comparison of groundwater and surface water for patterns
and levels of contamination by toxic substances. Environ. Scl. Techno!.
15: 1475-1481.
Pott, F. and A. Brockhaus. 1971. Verglelch der Enteralen und Pulmonalen
Resorptlonsquote von Blelverblndungen. Zentrabl. Bakt. Hyg. J. Or1g. B.
155: 1-17. (Cited In U.S. EPA, 1977)
Pueschel, S.M., L. KopHo and H. Schwachman. 1972. Children with an
Increased lead burden. A screening and follow up study. J. Am. Med.
Assoc. 222: 462-466. (Cited In U.S. EPA, 1980b)
RablnowHz, M.B., G.W. Wetherlll and J.D. Kopple. 1973. Lead metabolism 1n
the normal human: Stable Isotope studies. Science (London). 182: 725-727.
-36-
-------
Rablnowitz, M.B., G.W. Wetherlll and J.D. Kopple. 1974. Studies of human
lead metabolism by use of stable Isotype tracers. Environ. Health Perspect.
Exp. Issue. 7: 145-153. (Cited In U.S. EPA, 1980b)
Rablnowitz, M.B., G.W. Wetherlll and J.D. Kopple. 1976. Kinetic analysis
of lead metabolism 1n healthy humans. J. Cl1n. Invest. 58: 260-270.
Rablnowitz, M.B., G.W. Wetherlll and J.D. Kopple. 1977. Magnitude of lead
Intake from respiration 1n normal man. J. Lab. Clln. Med. 90: 238-248.
Randall, R.E.G., P. Bally and C.L. Soskolne. 1975. The effect of particle
size on absorption of Inhaled lead. J. Am. Ind. Hyg. Assoc. 36(3):
207-213. (Cited In U.S. EPA, 1977)
Relter, L.W., G.E. Anderson, J.W. Laskey and D.F. CahUl. .1975. Develop-
ment and behavioral changes 1n the rat during chronic exposure to lead.
Environ. Health Perspect. 12: 119-123. (Cited 1n U.S. EPA, 1977)
Roels, H.A., R.R. Lauwerys, J.P. Buchet and M.-Th. Vrelust. 1975. Response
of free erythrocyte porphyMn and urinary a-am1nolevu!1n1c add In men and
women moderately exposed to lead. Int. Arch. Arbeltsmed. 34: 97-108.
(Cited 1n U.S. EPA, 1980b)
Roels, H.A., J.-P. Buchet, R.R. Lauwerys, et al. 1980. Exposure to lead by
the oral and the pulmonary routes of children living in the vicinity of a
primary lead smelter. Environ. Res. 22: 81-94.
-37-
-------
Rom, W.N. 1976. Effects of lead on the female and reproduction: A review.
Ht. Sinai J. Med. 43: 542-552. (Cited 1n U.S. EPA, 1977)
Schroeder, H.A. and M. Mltchener. 1971. Toxic effects of trace elements on
reproduction of mice and rats. Arch. Environ. Health. 23: 102-106. (Cited
1n U.S. EPA, 1977, 1984; IARC, 1980)
Schroeder, H.A., J.J. Balassa and W.H. Vlnton, Jr. 1965. Chromium, cadmium
and lead In rats: Effects on life span, tumors and tissue levels. J. Nutr.
86: 51-66. (Cited In Schroeder et al., 1970; U.S. EPA, 1984)
Schroeder, H.A., M. Mltchener and A.P. Nason. 1970. Zirconium, niobium,
tin, vanadium and lead 1n rats: Llfeterm studies. J. Nutr. 100: 59-68.
(Cited 1n U.S. EPA, 1977, 1984; IARC, 1980)
Selander, S. and K. Cramer. 1970. Interrelationships between lead In
blood, lead In urine, and ALA 1n urine during lead work. Br. J. Ind. Med.
27: 28. (Cited 1n U.S. EPA, 1980b)
Shakerln, M. and J. Paloucek. 1965. Intranuclear Inclusions and renal
tumors In rats fed lead subacetate. Lab. Invest. 14: 592. (Cited 1n IARC,
1980)
Shakerln, M., J. Paloucek, R. Oyasu and G.M. Mass. 1965. Cardnogenesls 1n
rats due to dietary 2AAF and lead subacetate. Fed. Proc. 24: 684. (Cited
1n IARC, 1980)
-38-
-------
Six, K.M. and R.A. Goyer. 1970. Experimental enhancement of lead toxlclty
by low dietary calcium. J. Lab. CUn. Med. 76: 933-942. (Cited 1n U.S.
EPA, 1980b)
Six, K.M. and R.A. Goyer. 1972. The Influence of Iron deficiency on tissue
content and toxlclty of Ingested lead 1n the rat. J. Lab. din. Med. 79:
128-136. (Cited 1n U.S. EPA, 1980b)
Sobel, A.E., I.B. Wexler, D.D. Petrovsky and B. Kramer. 1938. Influence of
dietary calcium and phosphorus upon action of vitamin D 1n experimental lead
poisoning. Proc. Soc. Exp. Biol. Med. 38: 435-437. (Cited In U.S. EPA,
1980b)
Stowe, H.D. and R.A. Goyer. 1971. The reproductive ability and progeny of
FI lead-toxic rats. Fertll. SterH. 22: 755-760. (Cited 1n U.S. EPA,
1980b, 1984; IARC, 1980)
Tansslg, F.J. 1936. Abortion, spontaneous and Induced. St. Louis, Mosby.
Ill: 354. (Cited In U.S. EPA, 1977)
Tola, S., S. Hernberg, S. Asp and J. Nlkkanen. 1973. Parameters Indicative
of absorption and biological effect In new lead exposure: A prospective
study. Br. J. Ind. Med. 30: 134. (Cited In U.S. EPA, 1980b)
U.S. EPA. 1977. A1r Quality Criteria for Lead. U.S. EPA, ORD, Washington,
DC. EPA 600/8-77-017.
-39-
-------
U.S. EPA. 1980a. Guidelines and Methodology Used In the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45:79347-79357.
U.S. EPA. 1980b. Ambient Water Quality Criteria for Lead. Environmental
Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-057. NTIS PB
81-117681.
U.S. EPA. 1983a. Reportable Quantity for Lead (and compounds). Prepared
by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA
for the Office of Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1983b. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxldty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
U.S. EPA. 1983c. Review of lexicological Data 1n Support of Evaluation for
Carcinogenic Potential of: Lead Acetate. Prepared by the Carcinogen Assess-
ment Group, OHEA, Washington, DC, for the Office of Solid Waste and Emer-
gency Response, Washington, DC.
U.S. EPA. 1984. A1r Quality for Lead. Environmental Criteria and Assess-
ment Office, Research Triangle Park, NC. EPA 600/8-83-028B. NTIS PB
85-163996.
-40-
-------
Van Esch, 6.J. and R. Kroes. 1969. The Induction of renal tumours by
feeding basic lead acetate to mice and hamsters. Br. J. Cancer. 23:
765-771. (Cited 1n U.S. EPA, 1980b)
Van Esch, G.J., H. Van Genderen and H.H. V1nk. 1962. The Induction of
renal tumors by feeding basic lead acetate to rats. Br. J. Cancer. 16:
289. (Cited 1n U.S. EPA, 1980b)
Verma, M.M., S.R. Joshl and A.O. Adeyeml. 1974. MutagenlcHy and Infertil-
ity following administration of lead sub-acetate to Swiss male mice.
Exper1ent1a. 30(5): 486-487. (Cited In U.S. EPA, 1977)
Vermande-van Eck, G.J. and J.W. Melgs. 1960. Changes 1n the ovary of the
rhesus monkey after chronic lead Intoxication. FertH. Steril. 11:
-223-234. (Cited In U.S. EPA, 1977)
Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals,
2nd ed. Van Nostrand Relnhold Co., NY. p. 1085 and 1091.
Walter, S.O., A.J. Yankel and I.H. von Llndern. 1980. Age specific risk
factors for lead absorption 1n children. Arch. Environ. Health. 35: 53-58.
Weast, R.t Ed. 1980. CRC Handbook of Chemistry and Physics, 61st ed. CRC
Press, Boca Raton, FL. p. B110-B113.
Weller, C.V. 1915. The blastrophthorlc effect of chronic lead poisoning.
J. Med. Res. 33: 271. (Cited In U.S. EPA, 1977)
-41-
-------
* Wetherm, G.W., M. RablnowHz and J.D. Kopple. 1974. Sources and metabo-
lic pathways of lead 1n normal humans. Proc. Int. Symp. Environment and
Health, CDC, EPA, WHO, Paris, France, June. (Cited In U.S. EPA, 1980b)
WHO (World Health Organization). 1977. Environmental Health Criteria 3.
Lead. Geneva. (Cited 1n U.S. EPA, 1980b)
Yankel, A.J., I.H. von Llndern and S.O. Walter. 1977. The Silver Valley
lead study: The relationship of childhood lead poisoning and environmental
exposure. J. A1r Pollut. Control Assoc. 27: 763-767.
Zawlrska, B. and K. Medras. 1968. Tumours and disorders of porphyrln
metabolism 1n rats with chronic lead Intoxication. Zbl. Allg. Path. Ill:
1-12. (Ger.) (Cited 1n IARC, 1980; U.S. EPA, 1984)
Zawlrska, B. and K. Medras. 1972. The role of the kidneys 1n disorders of
porphyrln metabolism during cardnogenesls Induced with lead acetate. Arch.
Immunol. Ther. Exp. 20: 257-272. (Cited In U.S. EPA, 1983c)
Zlegler, E.E., et al. 1978. Absorption and retention of lead by Infants.
Pedlatr. Res. 12: 29. (Cited 1n U.S. EPA, 1980b)
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CO
I
r
APPENDIX *
Summary Table for Lead8
Experimental
Species Dose/Exposure
Inhalation
AIS NA NA
AIC human
Maximum mice 25 ppm In
composite drinking water,
score 4.25 mg/kg/day
(RVd=3.5)
Oral
AIS NA NA
AIC human NA
Acceptable Intake
Effect (AIS or AIC) Reference
NA ND NA
decreased 1.5 yg/mab U.S. EPA, 1984
hemoglobin
decreased survival 35 Schroeder and
of offspring MHchener, 1971
(RVe=10)
NA ND NA
decreased 50 vq/lc U.S. EPA, 1980b
hemoglobin
a429 yg/day has been estimated as a tolerable dally Intake for an adult from all sources combined
(WHO, 1977)
^Current air standard
cSuggested drinking water criterion level
NA = Not applicable; ND = not derived
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