United States
Environmental Protection
Agency
Environmental Criteria and
Assessment Office
Research Triangle Park NC 27711
EPA-600/8-83-028A
October 1983
External Review Draft
Research and Development
xvEPA
Air Quality
for Lead
Volume I of IV
Review
Draft
(Do Not
Cite or Quote)
NOTICE
This document is a preliminary draft. It has not been formally
released by EPA and should not at this stage be construed to
represent Agency policy. It is being circulated for comment on its
technical accuracy and policy implications.
-------
EPA-600/8-83-028A
October 1983
Draft External Review Draft
Do Not Quote or Cite
Air Quality Criteria
for Lead
Volume I
NOTICE
This document is a preliminary draft. It has not been formally released by EPA and should not at this stage
be construed to represent Agency policy. It is being circulated for comment on its technical accuracy and
policy implications.
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, N.C. 27711
-------
NOTICE
Mention of trade names or commercial products does not constitute
endorsement or recommendation for use.
1i
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ABSTRACT
The document evaluates and assesses scientific information on the health
and welfare effects associated with exposure to various concentrations of lead
in ambient air. The literature through 1983 has been reviewed thoroughly for
information relevant to air quality criteria, although the document is not
intended as a complete and detailed review of all literature pertaining to
lead. An attempt has been made to identify the major discrepancies in our
current knowledge and understanding of the effects of these pollutants.
Although this document is principally concerned with the health and
welfare effects of lead, other scientific data are presented and evaluated in
order to provide a better understanding of this pollutant in the environment.
To this end, the document includes chapters that discuss the chemistry and
physics of the pollutant; analytical techniques; sources, and types of
emissions; environmental concentrations and exposure levels; atmospheric
chemistry and dispersion modeling; effects on vegetation; and respiratory,
physiological, toxicological, clinical, and epidemiological aspects of human
exposure.
iii
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PRELIMINARY DRAFT
CONTENTS
VOLUME I
Chapter 1.
VOLUME II
Chapter 2.
Chapter 3.
Chapter 4.
Chapter 5.
Chapter 6.
Chapter 7.
Chapter 8.
VOLUME III
Chapter 9.
Chapter 10.
Chapter 11.
Executive Summary and Conclusions
Introduction
Chemical and Physical Properties
Sampling and Analytical Methods for Environmental Lead
Sources and Emissions
Transport and Transformation
Environmental Concentrations and Potential Pathways to Human Exposure
Effects of Lead on Ecosystems
Quantitative Evaluation of Lead and Biochemical Indices of Lead
Exposure in Physiological Media
Metaboli sm of Lead
Assessment of Lead Exposures and Absorption in Human Populations
Volume IV
Chapter 12. Biological Effects of Lead Exposure
Chapter 13. Evaluation of Human Health Risk Associated with Exposure to Lead
and Its Compounds
1-1
2-1
3-1
4-1
5-1
6-1
7-1
8-1
9-1
10-1
11-1
12-1
13-1
iv
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PRELIMINARY DRAFT
TABLE OF CONTENTS
CHAPTER 1
EXECUTIVE SUMMARY AND CONCLUSIONS
LIST OF FIGURES v
LIST OF TABLES vi
1. EXECUTIVE SUMMARY AND CONCLUSIONS 1-1
1.1 INTRODUCTION 1-1
1.2 ORGANIZATION OF DOCUMENT 1-3
1.3 CHEMICAL AND PHYSICAL PROPERTIES OF LEAD 1-4
1.4 SAMPLING AND ANALYTICAL METHODS FOR ENVIRONMENTAL LEAD 1-6
1.4.1 Sampling Techniques 1-7
1.4.2 Analytical Procedures 1-10
1.5 SOURCES AND EMISSIONS 1-13
1.6 TRANSPORT AND TRANSFORMATION 1-22
1.7 ENVIRONMENTAL CONCENTRATIONS AND POTENTIAL PATHWAYS
TO HUMAN EXPOSURE 1-34
1.7.1 Lead in Air 1-34
1.7.2 Lead in Soil and Dust 1-37
1.7.3 Lead in Food 1-38
1.7.4 Lead in Water 1-39
1.7.5 Baseline Exposures to Lead 1-40
1.7.6 Additional Exposures 1-45
Urban atmospheres 1-45
Houses with interior lead paint 1-47
Family gardens 1-47
Houses with lead plumbing 1-47
Residences near smelters and refineries 1-48
Occupational exposures 1-48
Secondary occupati onal exposure 1-49
Special habits or activities 1-49
1.8 EFFECTS OF LEAD ON ECOSYSTEMS 1-52
1.8.1 Effects on Plants 1-57
1.8.2 Effects of Animals 1-61
1.8.3 Effects on Microorganisms 1-63
1.8.4 Effects on Ecosystems 1-64
1.8.5 Summary 1-66
1.9 QUANTITATIVE EVALUATION OF LEAD AND BIOCHEMICAL INDICES OF LEAD
EXPOSURE IN PHYSIOLOGICAL MEDIA . 1-67
1.9.1 Determinations of Lead in Biological Media 1-67
Measurements of 1 ead i n bl ood 1-68
Lead i n pi asma 1-69
Lead in teeth 1-69
Lead in hair 1-69
Lead i n uri ne 1-70
Lead i n other ti ssues 1-70
Quality assurance procedures in lead analyses 1-70
1.9.2 Determination of Erythrocyte Porphyrin (Free Erythrocyte
Protoporphyrin, Zi.nc Protoporphyrin) 1-71
1.9.3 Measurement of Urinary Coproporphyrin 1-72
v
CHP1D/B 9/30/83
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PRELIMINARY DRAFT
TABLE OF CONTENTS (continued).
Page
1.9.4 Measurement of Delta-Aminolevulinic Acid Dehydrase Activity 1-72
1.9.5 Measurement of Delta-Aminolevulinic Acid in Urine and
Other Media 1-73
1.9.6 Measurement of Pyrimidine-5'-Nucleotidase Activity 1-74
1.10 METABOLISM OF LEAD 1-74
1.10.1 Lead Absorption in Humans and Animals 1-75
Respi ratory absorpti on of 1 ead 1-75
Gastrointestinal absorption of lead 1-75
Percutaneous absorption of lead 1-76
Transplacental transfer of lead 1-76
1.10.2 Distribution of Lead in Humans and Animals 1-77
1.10.2.1 Lead in Blood 1-77
1.10.2.2 Lead Levels in Tissues 1-77
Soft ti ssues 1-78
Mineralizing tissue 1-78
Chelatable lead 1-79
Animal studies 1-79
1.10.3 Lead Excretion and Retention in Humans and Animals 1-80
Human studi es 1-80
Animal studies 1-81
1.10.4 Interactions of Lead with Essential Metals and Other Factors 1-81
Human studies 1-81
Animal studies 1-82
1.10.5 Interrelationships of Lead Exposure with Exposure Indicators
and Ti ssue Lead Burdens 1-82
Temporal charactersitics of internal indicators
of 1 ead exposure 1-83
Biological aspects of external exposure-
internal indicator relationships 1-83
Internal indicator-tissue lead relationships 1-83
1.10.6 Metabolism of Lead Alkyls 1-84
Absorption of lead alkyls in humans and animals 1-84
Biotransformation and tissue distribution of lead alkyls 1-85
Excretion of lead alkyls .' 1-85
1.11 ASSESSMENT OF LEAD EXPOSURES AND ABSORPTION IN HUMAN POPULATIONS 1-85
1.11.1 Levels of Lead and Demographic Covariates
in U.S. Populations 1-86
1.11.2 Blood Lead vs. Inhaled Air Lead Relationships 1-92
1.11.3 Dietary Lead Exposures Including Water 1-96
1.11.4 Studies Relating Lead in Soil and Dust to Blood Lead 1-97
1.11.5 Pai nt Lead Exposures 1-98
1.11.6 Specific Source Studies 1-99
1.11.7 Primary Smelters Populations 1-102
1.11.8 Secondary Exposure of Chi 1dren 1-105
1.12 BIOLOGICAL EFFECTS OF LEAD EXPOSURE 1-106
1.12.1 Introduction 1-106,
1.12.2 Subcellular Effects of Lead 1-106
1.12.3 Effects of Lead on Heme Biosynthesis, Erythropoiesis, and
Erythrocyte Physiology in Humans and Animals 1-109>
1.12.4 Neurotoxic Effects of Lead
1.12.5 Effects of Lead on the Kidney ,
CHP1D/B 9/30/84
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PRELIMINARY DRAFT
TABLE OF CONTENTS (continued).
Page
1.12.6 Effects of Lead on Reproduction and Development 1-121
1.12.7 Genotoxic and Carcinogenic Effects of Lead 1-122
1.12.8 Effects of Lead on the Immune System 1-123
1.12.9 Effects of Lead on Other Organ Systems 1-123
1.13 EVALUATION OF HUMAN HEALTH RISKS ASSOCIATED WITH EXPOSURE TO LEAD AND
ITS COMPOUNDS 1-123
1.13.1 Introduction 1-123
1.13.2 Exposure Aspects 1-124
1.13.3 Lead Metabolism: Key Issues for Human Health Risk Evaluation 1-130
1.13.4 Biological Effects of Lead Relevant to the General Human Population . 1-136
1.13.5 Dose-Response Relationships for Lead Effects in Human Populations ... 1-145
1.13.6 Populations at Risk 1-148
1.13.7 Summary and Conclusions 1-151
vii
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PRELIMINARY DRAFT
LIST OF TABLES
Table Page
1-1 Estimated atmospheric lead emissions for the United States, 1981 and
the worl d 1-17
1-2 Summary of surrogate and vegetation surface deposition of lead 1-30
1-3 Estimated global deposition of atmospheric lead 1-31
1-4 Atmospheric lead in urban, rural, and remote areas of the world 1-35
1-5 Background lead in basic food crops and meats 1-39
1-6 Summary of environmental concentrations of lead 1-41
1-7 Summary by age and sex of estimated average levels of lead ingested
from mi 1 k and foods 1-43
1-8 Summary of baseline human exposures to lead 1-46
1-9 Weighted geometric mean blood lead levels from NHANES II survey by
degree of urbanization of place of residence in the U.S. by age
and race, United States 1976-80 1-89
1-10 Summary of pooled geometric standard deviations and estimated
analytic errors 1-93
1-11 Summary of blood inhalation slopes pg/dl per (jg/m? 1-94
1-12 Estimated contribution of leaded gasoline to blood lead by inhalation
and non-inhalation pathways 1-101
1-13 Summary of basel ine human exposures to 1 ead 1-126
1-14 Relative baseline human lead exposures expressed per kilogram body weight 1-127
1-15 Summary of potential additive exposures to lead 1-128
1-16 Direct contributions of air lead to blood lead (PbB) in adults at fixed
i nputs of water and food 1 ead 1-135
1-17 Direct contributions of air lead to blood lead in children at fixed inputs
of water and food 1 ead 1-135
1-18 Contributions of dust/soil lead to blood lead in children at fixed inputs
of air, food, and water lead 1-135
1-19 Summary of lowest observed effect levels for key lead-induced health effects
in adults 1-139
1-20 Summary of lowest observed effect levels for key lead-induced health effects
in children 1-141
1-21 EPA-estimated percentage of subjects with ala-u exceeding limits for
various blood lead levels 1-147
1-22 Provisional estimate of the number of individuals in urban and rural
population segments at greatest potential risk to lead exposure 1-151
viii
CHP1D/B 9/30/83
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PRELIMINARY DRAFT
LIST OF FIGURES
Figure Page
1-1 Pathways of lead exposure from the environment to man 1-2
1-2 Metal complexes of lead 1-5
1-3 Softness parameters of metals 1-6
1-4 Chronological record of the relative increase of lead in snow strata,
pond and lake sediments, marine sediments, and tree rings. The data
are expressed as a ratio of the latest year of the record and should
not be interpreted to extend back in time to natural or uncontaminated
levels of lead concentration 1-14
1-5 The global lead production has changed historically in response to
major economic and political events. Increases in lead production
(note log scale) correspond approximately to historical increases
in lead emissions shown in Figure 1-4 1-15
1-6 Locations of major lead operations in the United States 1-18
1-7 Trend in lead content of U.S. gasolines, 1975-1982 1-20
1-8 Relationship between lead consumed in gasoline and composite
maximum quarterly average lead levels, 1975-1980 1-21 ,
1-9 Profile of lead concentrations in the central northeast Pacific. Values
below 1000 m are an order magnitude lower than reported by Tatsumoto and
Patterson (1963) and Chow and Patterson (1966) 1-26
1-10 Lead concentration profile in snow strata of northern Greenland 1-27
1-11 Variation of lead saturation capacity with cation exchange capacity in
soi 1 at selected pH val ues 1-32
1-12 This figure depicts cycling process within major components of a terrestrial
ecosystem, i.e. primary producers, grazers, and decomposers. Nutrient and
non-nutrient elements are stored in reservoirs within these components.
Processes that take place within reservoirs regulate the flow of elements
between reservoirs along established pathways. The rate of flow is in
part a function of the concentration in the preceding reservoir. Lead
accumulates in decomposer reservoirs which have a high binding capacity
for this metal. It is likely that the rate of flow away from these
reservoirs has increased in past decades and will continue to increase
for some time until the decomposer reservoirs are in equilibrium with the
entire ecosystem. Inputs to and outputs from the ecosystems as a whole
are not shown 1-54
1-13 Geometric mean blood lead levels by race and age for younger children in the
NHANES II study, and the Kellogg/Silver Valley and New York childhood
screening studies 1-87
1-14 Average blood lead levels of U.S. population 6 months - 74 years. United
States, February 1976 - February 1980, based on dates of examination of
NHANES II examinees with blood lead determinations 1-90
1-15 Time dependence of blood lead for blacks, aged 24 to 35 months, in New York
City and Chicago 1-91
1-16 Change in 2t?*Pb/5t>7Pb ratios in petrol, airborne particulate and
blood from 1974 to 1981 1-100
1-17 Geometric mean blood lead levels of New York City children (aged 25-36
months) by ethnic group, and ambient air lead concentration vs.
quarterly sampling period, 1970-1976 1-103
1-18 Geometric mean blood lead levels of New York City children (aged 25-36
months) by ethnic group, and estimated amount of lead present in gasoline
sold in New York, New Jersey, and Connecticut vs. quarterly sampling
period, 1970-1976 1-104
ix
CHP1D/B 9/30/83
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PRELIMINARY DRAFT
LIST Of FIGURES (continued).
Mgure Page
1-19 Dose-response for elevation of EP as a function of blood lead level using
probit analysis 1-146
1-20 Dose-response curve for FEP as a function of blood lead level: in sub-
populations 1-146
1-21 EPA calculated dose-response for ALA-U 1-147
CHP1D/B 9/30/83
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AUTHORS AND CONTRIBUTORS
Chapter 1: Executive Summary
Principal Author
Dr. Lester D. Grant
Director
Environmental Criteria and Assessment Office
Environmental Protection Agency
MD-52
Research Triangle Park, NC 27711
Contributing Authors:
Dr. J. Michael Davis
Environmental Criteria and
Assessment Office
MD-52
Research Triangle Park, NC 27711
Dr. Vic Hasselblad
Biometry Division
Health Effects Research Laboratory
MD-55
Research Triangle Park, NC 27711
Dr. Paul Mushak
Department of Pathology
School of Medicine
University of North Carolina
Chapel Hill, NC 27514
Dr. Robert W. Eli as
Environmental Criteria and
Assessment Office
MD-52
Research Triangle Park, NC 27711
Dr. Dennis J. Kotchmar
Environmental Criteria and
Assessment Office
MD-52
Research Triangle Park, NC 27711
Dr. David E. Weil
Environmental Criteria and
and Assessment Office
MD-52
Research Triangle Park, NC 27711
XI
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PRELIMINARY DRAFT
LIST OF ABBREVIATIONS
AAS
Ach
ACTH
ADCC
ADP/0 ratio
AIDS
AIHA
All
ALA
ALA-D
ALA-S
ALA-U
APDC
APHA
ASTM
ASV
ATP
B-cells
Ba
BAL
BAP
BSA
BUN
BW
C.V.
CaBP
CaEDTA
CBD
Cd
CDC
CEC
CEH
CFR
CMP
CNS
CO
COHb
CP-U
cBah
D.F.
DA
DCMU
DDP
DNA
DTH
EEC
EEC
EMC
EP
EPA
Atomic absorption spectrometry
Acetylcholine
Adrenocoticotrophic hormone
Antibody-dependent cell-mediated cytotoxicity
Adenosine diphosphate/oxygen ratio
Acquired immune deficiency syndrome
American Industrial Hygiene Association
Angiotensin II
Aminolevulinic acid
Aminolevulinic acid dehydrase
Aminolevulinic acid synthetase
Aminolevulinic acid in urine
Ammonium pyrrolidine-dithiocarbamate
American Public Health Association
Amercian Society for Testing and Materials
Anodic stripping voltammetry
Adenosine triphosphate
Bone marrow-derived lymphocytes
Barium
British anti-Lewisite (AKA dimercaprol)
benzo(a)pyrene
Bovine serum albumin
Blood urea nitrogen
Body weight
Coefficient of variation
Calcium binding protein
Calcium ethylenediaminetetraacetate
Central business district
Cadmium
Centers for Disease Control
Cation exchange capacity
Center for Environmental Health
reference method
Cytidine monophosphate
Central nervous system
Carbon monoxide
Carboxyhemoglobin
Urinary coproporphyrin
plasma clearance of p-aminohippuric acid
Copper
Degrees of freedom
Dopamine
[3-(3,4-dichlorophenyl)-l,l-dimethylurea
Differential pulse polarography
Deoxyribonucleic acid
Delayed-type hypersensitivity
European Economic Community
Electroencephalogram
Encephalomyocarditis
Erythrocyte protoporphyrin
U.S. Environmental Protection Agency
TCPBA/D
xii
9/20/83
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PRELIMINARY DRAFT
LIST OF ABBREVIATIONS (continued).
FA Fulvic acid
FDA Food and Drug Administration
Fe Iron
FEP Free erythrocyte protoporphyrin
FY Fiscal year
G.M. Grand mean
G-6-PD Glucose-6-phosphate dehydrogenase
GABA Gamma-aminobutyric acid
GALT Gut-associated lymphoid tissue
GC Gas chromatography
GFR Glomerular filtration rate
HA Humic acid
Hg Mercury
hi-vol High-volume air sampler
HPLC High-performance liquid chromatography
i.m. Intramuscular (method of injection)
i.p. Intraperitoneally (method of injection)
i.v. Intravenously (method of injection)
IAA Indol-3-ylacetic acid
IARC International Agency for Research on Cancer
ICD International classification of diseases
ICP Inductively coupled plasma
IDMS Isotope dilution mass spectrometry
IF Interferon
ILE Isotopic Lead Experiment (Italy)
IRPC International Radiological Protection Commission
K Potassium
LAI Leaf area index
LDH-X Lactate dehydrogenase isoenzyme x
LC,-n Lethyl concentration (50 percent)
LDcQ Lethal dose (50 percent)
LH Luteinizing hormone
LIPO Laboratory Improvement Program Office
In National logarithm
LPS Lipopolysaccharide
LRT Long range transport
mRNA Messenger ribonucleic acid
ME Mercaptoethanol
MEPP Miniature end-plate potential
MES Maximal electroshock seizure
MeV Mega-electron volts
MLC Mixed lymphocyte culture
HMD Mass median diameter
MMED Mass median equivalent diameter
Mn Manganese
MND Motor neuron disease
MSV Moloney sarcoma virus
MTD Maximum tolerated dose
n Number of subjects
N/A Not Available
xiii
TCPBA/D 9/20/83
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PRELIMINARY DRAFT
LIST OF ABBREVIATIONS
NA
NAAQS
NADB
NAMS
MAS
NASN
NBS
NE
NFAN
NFR-82
NHANES II
Ni
OSHA
P
P
PAH
Pb
PBA
Pb(Ac)?
PbB *
PbBrCl
PBG
PFC
PH
PHA
PHZ
PIXE
PMN
PND
PNS
ppm
PRA
PRS
PWM
Py-5-N
RBC
RBF
RCR
redox
RES
RLV
RNA
S-HT
SA-7
scm
S.D.
SDS
S.E.M.
SES
SCOT
Not Applicable
National ambient air quality standards
National Aerometric Data Bank
National Air Monitoring Station
National Academy of Sciences
National Air Surveillance Network
National Bureau of Standards
Norepinephrine
National Filter Analysis Network
Nutrition Foundation Report of 1982
National Health Assessment and Nutritional Evaluation Survey II
Nickel
Occupational Safety and Health Administration
Potassium
Significance symbol
Para-aminohippuric acid
Lead
Air lead
Lead acetate
concentration of lead in blood
Lead (II) bromochloride
Porphobilinogen
Plaque-forming cells
Measure of acidity
Phytohemaggluti ni n
Polyacrylamide-hydrous-zirconia
Proton-induced X-ray emissions
Polymorphonuclear leukocytes
Post-natal day
Peripheral nervous system
Parts per million
Plasma renin activity
Plasma renin substrate
Pokeweed mitogen
Pyrimide-B'-nucleotidase
Red blood cell; erythrocyte
Renal blood flow
Respiratory control ratios/rates
Oxidation-reduction potential
Reticuloendothelial system
Rauscher leukemia virus
Ribonucleic acid
Serotonin
Simian adenovirus
Standard cubic meter
Standard deviation
Sodium dodecyl sulfate
Standard error of the mean
Socioeconomic status
Serum glutamic oxaloacetic transaminase
xiv
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PRELIMINARY DRAFT
LIST OF ABBREVIATIONS (continued).
SLAMS
SMR
Sr
SRBC
SRMs
STEL
SW voltage
T-cells
t-tests
TBL
TEA
TEL
TIBC
TML
TMLC
TSH
TSP
U.K.
UMP
USPHS
VA
VE*R
WHO
XRF
}T
Zn
2PP
Surface immunoglobulin
State and local air monitoring stations
Standardized mortality ratio
Strontium
Sheep red blood cells
Standard reference materials
Short-term exposure limit
Slow-wave voltage
Thymus-derived lymphocytes
Tests of significance
Tri-n-butyl lead
Tetraethyl-ammonium
Tetraethyllead
Total iron binding capacity
Tetramethyllead
Tetramethyllead chloride
Thyroid-stimulating hormone
Total suspended particulate
United Kingdom
Uridine monophosphate
U.S. Public Health Service
Veterans Administration
Deposition velocity
Visual evoked response
World Health Organization
X-Ray fluorescence
Chi squared
Zinc
Erythrocyte zinc protoporphyrin
MEASUREMENT ABBREVIATIONS
dl
ft
g
g/gal
g/ha-mo
km/hr
1/min
mg/km
mm
(jmol
ng/cm2
nm
nM
sec
deciliter
feet
gram
gram/gallon
gram/hectare-month
kilometer/hour
liter/minute
mi 11i gram/ki1ometer
mjcrogram/cubic meter
millimeter
micrometer
nanograms/square centimeter
namometer
nanomole
second
xv
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PRELIMINARY DRAFT
1. EXECUTIVE SUMMARY AND CONCLUSIONS
1.1 INTRODUCTION
This criteria document evaluates and assesses scientific information on the health and
welfare effects associated with exposure to various concentrations of lead in ambient air.
According to Section 108 of the Clean Air Act of 1970, as amended in June 1974, a cri-
teria document for a specific pollutant or class of pollutants shall:
. . . accurately reflect the latest scientific knowledge useful in indicating
the kind and extent of all identifiable effects on public health or welfare which
may be expected from the presence of such pollutant in the ambient air, in varying
quantities.
Air quality criteria are of necessity based on presently available scientific data, which
in turn reflect the sophistication of the technology used in obtaining those data as well as
the magnitude of the experimental efforts expended. Thus air quality criteria for atmospheric
pollutants are a scientific expression of current knowledge and uncertainties. Specifically
air quality criteria are expressions of the scientific knowledge of the relationships between
various concentrations--averaged over a suitable time period--of pollutants in the same atmos-
phere and their adverse effects upon public health and the environment. Criteria are issued
as a basis for making decisions about the need for control of a pollutant and as a basis for
development of air quality standards governing the pollutant. Air quality criteria are
descriptive; that is, they describe the effects that have been observed to occur as a result
of external exposure at specific levels of a pollutant. In contrast, air quality standards
are prescriptive; that is, they prescribe what a political jurisdiction has determined to be
the maximum permissible exposure for a given time in a specified geographic area.
This criteria document is a revision of the previous Air Quality Criteria Document for
Lead (EPA-600/8-77-017) published in December, 1977. This revision is mandated by the Clean.
Air Act (Sect. 108 and 109), as amended UVS.C. §§7408 and 7409. The criteria document sets
forth what is known about the effects of lead contamination in the environment on human health
and welfare. This requires that the relationship between levels of exposure to lead, via all
routes and averaged over a suitable time period, and the biological responses to those levels
be carefully assessed. Assessment of exposure must take into consideration the temporal and
spatial distribution of lead and its various forms in the environment. Thus, the literature
through June, 1983, has been reviewed thoroughly for information relevant to air quality cri-
teria, for lead, but the document is not intended as a complete and detailed review of all
literature pertaining to lead. Also, efforts are made to identify major discrepancies in our
current knowledge and understanding of the effects of lead compounds.
SUMPB/D 1-1 9/30/83
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PRELIMINARY DRAFT
Lead is a naturally occurring element that may be found in the earth's crust and in all
components of the biosphere. It may be found in water, soil, plants, animals, and humans.
Because lead also occurs in ore bodies that have been mined for centuries by man, this metal
has also been distributed throughout the biosphere by the industrial activities of man. Of
particular importance to the human environment are emissions of lead to'the atmosphere. The
sources of these emissions and the pathways of lead through the environment to man are shown
in Figure 1-1. This figure shows natural inputs to soil by crustal weathering and
anthropogenic inputs to the atmosphere from automobile emissions and stationary industrial
sources. Natural emissions of lead to the atmosphere from volcanoes and windblown soil are of
minor importance.
SUMPB/D
LIVER*
KIDNEY
x\
FECES URINE
Figure 1-1. Pathways of lead exposure from the environment to man.
1-2
9/30/83
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PRELIMINARY DRAFT
From these emission sources, lead moves through the atmosphere to various components of
the human environment. Lead is deposited on soil and plants and in animals, becoming incor-
porated into the food chain of man. Atmospheric lead is a major component of household and
street dust; lead is also inhaled directly from the atmosphere.
1.2 ORGANIZATION OF DOCUMENT
This document focuses primarily on lead as found in its various forms in the ambient
atmosphere; in order to assess its effects on human health, however, the distribution and bio-
logical availability of lead in other environmental media have been considered. The rationale
for structuring the document was based primarily on the two major questions of exposure and
response. The first portion of the do'cument is devoted to lead in the environment—its physi-
cal and chemical properties; the monitoring of lead in various media; sources, emissions, and
concentrations of lead; and the transport and transformation of lead within environmental
media. The latter portion is devoted to biological responses and effects on human health and
ecosystems.
In order to facilitate printing, distribution, and review of the present draft materials,
this First External Review Draft of the revised EPA Air Quality Criteria Document for Lead is
being released in four volumes. The first volume (Volume I) contains this executive summary
and conclusions chapter (Chapter 1) for the entire document. Volume II contains Chapters 2-8,
which include: the introduction for the document (Chapter 2); discussions of the above listed
topics concerning lead in the environment (Chapters 3-7); and evaluation of lead effects on
ecosystems (Chapter 8). The remaining two volumes contain Chapters 9-13, which deal with the
extensive available literature relevant to assessment of health effects associated with lead
exposure.
An effort has been made to limit the document to a highly critical assessment of the sci-
entific data base. The scientific literature has been reviewed through June 1983. The refer-
ences cited do not constitute an exhaustive bibliography of all available lead-related litera-
ture but they are thought to be sufficient to reflect the current state of knowledge on those
issues most relevant to the review of the air quality standard for lead.
The status of control technology for lead is not discussed in this document. For informa-
tion on the subject, the reader is referred to appropriate control technology documentation
published by the Office of Air Quality Planning and Standards (OAQPS), EPA. The subject of
"adequate margin of safety" stipulated in Section 108 of the Clean Air Act also is not expli-
citly addressed here; this topic will be considered in depth by EPA's Office of Air Quality
Planning and Standards in documentation prepared as a part of the process of revising the Na-
tional Ambient Air Quality Standard (NAAQS) for Lead.
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1.3 CHEMICAL AND PHYSICAL PROPERTIES OF LEAD
Lead is a gray-white metal of bright luster that, because of its easy isolation and low
melting point, was among the first of the metals to be extensively utilized by man. Lead was
used as early as 2000 B.C. by the Phoenicians. The most abundant ore is galena, from which
metallic lead is readily smelted. The metal is soft, malleable, and ductile, a poor
electrical conductor, and highly impervious to corrosion. This unique combination of physical
properties has led to its use in piping and roofing, and in containers for corrosive liquids.
The metal and the dioxide are used in storage batteries, and organolead compounds are used in
gasoline additives to boost octane levels. Since lead occurs in highly concentrated ores from
which it is readily separated, the availability of lead is far greater than its natural abun-
dance would suggest. The great environmental significance of lead is the result both of its
utility and of its availability.
The properties of organolead compounds (i.e., compounds containing bonds between lead and
carbon) are entirely different from those of the inorganic compounds of lead. Because of their
use as antiknock agents in gasoline and other fuels, the most important organolead compounds
have been the tetraalkyl compounds tetraethyllead (TEL) and tetramethyllead (TML). These lead
compounds are removed from internal combustion engines by a process called lead scavenging, in
which they react in the combustion chamber with halogenated hydrocarbon additives (notably
ethylene dibromide and ethylene dichloride) to form lead halides, usually bromochlorolead(II).
The donor atoms in a metal complex could be almost any basic atom or molecule; the only
requirement is that a donor, usually called a ligand, must have a pair of electrons available
for bond formation. In general, the metal atom occupies a central position in the complex, as
exemplified by the lead atom in tetramethyllead (Figure l-2a) which is tetrahedrally sur-
rounded by four methyl groups. In these simple organolead compounds, the lead is usually pre-
sent as Pb(IV), and the complexes are relatively inert. These simple ligands, which bind to
metal at only a single site, are called monodentate ligands. Some ligands, however, can bind
to the metal atom by more than one donor atom, so as to form a heterocyclic ring structure.
Rings of this general type are called chelate rings, and the donor molecules which form them
are called polydentate ligands or chelating agents. In the chemistry of lead, chelation nor-
mally involves Pb(II). A wide variety of biologically significant chelates with ligands
such as amino acids, peptides, and nucleotides are known. The simplest structure of this
type occurs with the amino acid glycine, as represented in Figure l-2b for a 1:2
(metal:ligand) complex. The importance of chelating agents in the present context is their
widespread use in the treatment of lead and other metal poisoning.
SUMPB/D 1-4 9/30/83
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H3C
CH3
Pb'
H3C CH3
(a)
NH2
CH,
H2O
Pb
H2O
(b)
(MM,
CH2
^C
Figure 1-2. Metal complexes of lead.
Metals are often classified according to some combination of their electronegativity,
ionic radius, and formal charge. These parameters are used to construct empirical classifi-
cation schemes of relative hardness or softness. In these schemes, "hard" metals form strong
bonds with "hard" anions and, likewise, "soft" metals bond with "soft" anions. Some metals
are borderline, having both soft and hard character. Pb(II), although borderline, demon-
strates primarily soft character (Figure 1-3). The term Class A may also be used to refer to
hard metals, and Class B to soft metals. Since Pb(II) is a relatively soft (or class B) metal
ion, it forms strong bonds to soft donor atoms like the sulfur atoms in the cysteine residues
of proteins and enzymes. In living systems, lead atoms bind to these peptide residues in pro-
teins, thereby changing the tertiary structure of the protein or blocking a substrate's
approach to the active site of an enzyme. This prevents the proteins from carrying out their
functions. As has been demonstrated in several studies (Jones and Vaughn, 1978; Williams and
Turner, 1981; Williams et al., 1982), there is an inverse correlation between the LD5Q values
of metal complexes and the chemical softness parameter. Lead(II) has a higher softness para-
meter than either cadmium(II) or mercury(II), so lead(II) compounds would not be expected to
be as toxic as their cadmium or mercury analogues.
The role of the chelating agents is to compete with the peptides for the metal by forming
stable chelate complexes that can be transported from the protein and eventually be excreted
by the body. For simple thermodynamic reasons, chelate complexes are much more stable than
monodentate metal complexes, and it is this enhanced stability that is the basis for their
ability to compete favorably with proteins and other ligands for the metal ions.
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CLASS B OR COVALENT INDEX, X*mr
9.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
ft t *
• i i i i i i i i " r / 1
t Au-
t .
• Ag- Pd'' 2> 3 ^
_ • ' PbllV)
• Ti- Hg2'
• Ti2-
_$Cu- CLASS B
•Pb" •Sb(.ll)
— Sn"0 mr,.>-
^F *->u AsMII )
• Co'' In2' * 0
_ Fe"« •Ni" • •Fe,. Sn(IV) —
CrJ-
Ti" t^m Zn"
— Mn' • v' Ga' * BORDERLINE —
_ Gd" Lu' —
Mg> 9 • »Sc' «
Cs- Ba2' • • y!. AC
J»K' •••Ca- ^ -
^Na' SrJ •
• Be'
~~ L' CLASS A
I I I I I I i I ,,l ,J
024 6 8 10 12 14 16 20 23
CLASS A OR IONIC INDEX, Z'/r
Figure 1-3. Softness parameters of metals.
Source: Nieboer and Richardson (1980).
It should be noted that both the stoichiometry and structures of metal chelates depend
upon pH, and that structures different from those manifest in solution may occur in crystals.
It will suffice to state, however, that several ligands can be found that are capable of suf-
ficiently strong chelation with lead present in the body under physiological conditions to
permit their use in the effective treatment of lead poisoning.
1.4 SAMPLING AND ANALYTICAL METHODS FOR ENVIRONMENTAL LEAD
Lead, like all criteria pollutants, has a designated Reference Method for monitoring and
analysis as required in State Implementation Plans for determining compliance with the lead
National Ambient Air Quality Standard. The Reference Method uses a high volume sampler (hi-
vol) for sample collection and atomic absorption spectrometry (AAS) for analysis.
For a rigorous quality assurance program, it is essential that investigators recognize
all sources of contamination and use every precaution to eliminate them. Contamination occurs
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on the surfaces of collection containers and devices, on the hands and clothing of the inves-
tigator, in the chemical reagents, in the laboratory atmosphere, and on the labware and tools
used to prepare the sample for analysis.
1.4.1 Sampling Techniques
Sampling strategy encompasses site selection, choice of instrument used to obtain repre-
sentative samples, and choice of method used to preserve sample integrity. In the United States,
some sampling stations for air pollutants have been operated since the early 1950's. These
early stations were a part of the National Air Surveillance Network (NASN), which has now
become the National Filter Analysis Network (NFAN). Two other types of networks have been
established to meet specific data requirements. State and Local Air Monitoring Stations
(SLAMS) provide data from specific areas where pollutant concentrations and population densi-
ties are the greatest and where monitoring of compliance to standards is critical. The Na-
tional Air Monitoring Station (NAMS) network is designed to serve national monitoring needs,
including assessment of national ambient trends. SLAMS and NAMS stations are maintained by
state and local agencies and the air samples are analyzed in their laboratories. Stations in
the NFAN network are maintained by state and local agencies, but the samples are analyzed by
laboratories in the U.S. Environmental Protection Agency, where quality control procedures are
rigorously maintained.
Data from all three networks are combined into one data base, the National Aerometric
Data Bank (NADB). These data may be individual chemical analyses of a 24-hour sampling period
arithmetically averaged over a calendar period, or chemical composites of several filters used
to determine a quarterly composite. Data are occasionally not available for a given location
because they do not conform to strict statistical requirements.
In September, 1981, EPA promulgated regulations establishing ambient air monitoring and
data reporting requirements for lead comparable to those already established in May of 1979
for the other criteria pollutants. Whereas sampling for lead is accomplished when sampling
for total suspended particulate (TSP), the designs of lead and TSP monitoring stations must be
complimentary to insure compliance with the NAMS criteria for each pollutant.
There must be at least two SLAMS sites for lead in any area that has a population greater
than 500,000 and any area where lead concentration currently exceeds the ambient lead standard
(1.5 pg/m3) or has exceeded it since January 1, 1974.
To clarify the relationship between monitoring objectives and the actual siting of a mon-
itor, the concept of a spatial scale of representativeness was developed. The spatial scales
are discribed in terms of the physical dimensions of the air space surrounding the monitor
throughout which pollutant concentrations are fairly similar.
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The time scale may also be an important factor. Siting criteria must include sampling
times sufficiently long to include average windspeed and direction, or a sufficient number of
samples must be collected over short sampling periods to provide an average value consistent
with a 24-hour exposure.
Airborne lead is primarily inorganic particulate matter but may occur in the form of or-
ganic gases. Devices used for collecting samples of ambient atmospheric lead include the
standard hi-vol sampler and a variety of other collectors employing filters, impactors,
impingegers, or scrubbers, either separately or in combination, that measure lead in ug/m3.
2
Some samplers measure lead deposition expressed in ug/cm ; some instruments separate parti-
cles by size. As a general rule, particles smaller in aerodynamic diameter than 2.5 urn are
classified as "fine", and those larger than 2.5 (jm as "coarse."
The present SLAMS and NAMS employ the standard hi-vol sampler (U.S. Environmental Protec-
tion Agency, 1971) as part of their sampling networks. As a Federal Reference Method Sampler,
the hi-vol operates with a specific flow rate of 1600 to 2500 m3 of air per day
When sampling ambient lead with systems employing filters, it is likely that vapor-phase
organolead compounds will pass through the filter media. The use of bubblers downstream from
the filter containing a suitable reagent or absorber for collection of these compounds has
been shown to be effective. Organolead may be collected on iodine crystals, adsorbed on acti-
vated charcoal, or absorbed in an iodine monochloride solution. In one experiment, Purdue et
al. (1973) operated two bubblers in series containing iodine monochloride solution. One hun-
dred percent of the lead was recovered in the first bubbler.
Sampling of stationary sources for lead requires the use of a sequence of samplers in the
smokestack. Since lead in stack emissions may be present in a variety of physical and chemical
forms, source sampling trains must be designed to trap and retain both gaseous and particulate
lead.
Three principal procedures have been used to obtain samples of auto exhaust aerosols for
subsequent analysis for lead compounds: a horizontal dilution tunnel, plastic sample collec-
tion bags, and a low residence time proportional sampler. In each procedure, samples are air
diluted to simulate roadside exposure conditions. In the most commonly used procedure, the
air dilution tube segregates fine combustion-derived particles from larger lead particles.
Such tunnels of varying lengths have been limited by exhaust temperatures to total flows above
approximately 11 nrVmin. Similar tunnels have a centrifugal fan located upstream, rather than
a positive displacement pump located downstream. This geometry produces a slight positive
pressure in the tunnel and expedites transfer of the aerosol to holding chambers for studies
of aerosol growth. However, turbulence from the fan may affect the sampling efficiency.
Since the total exhaust plus dilution airflow is not held constant in this system, potential
errors can be reduced by maintaining a very high dilution air/exhaust flow ratio.
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In the bag technique, auto emissions produced during simulated driving cycles are air-
diluted and collected in a large plastic bag. The aerosol sample is passed through a filtra-
tion or impaction sampler prior to lead analysis. This technique may result in errors of
aerosol size analysis because of condensation of low vapor pressure organic substances onto
the lead particles.
To minimize condensation problems, a third technique, a low residence time proportional
sampling system, has been used. It is based on proportional sampling of raw exhaust, again
diluted with ambient air followed by filtration or impaction. Since the sample flow must be a
constant proportion of the total exhaust flow, this technique may be limited by the response
time of the equipment to operating cycle phases that cause relatively small transients in the
exhaust flow rate.
Other primary environmental media that may be affected by airborne lead include precipi-
tation, surface water, soil, vegetation, and foodstuffs. The sampling plans and the sampling
methodologies used in dealing with these media depend on the purpose of the experiments, the
types of measurements to be carried out, and the analytical technique to be used.
Lead at the start of a rain event is higher in concentration than at the end, and rain
striking the canopy of a forest may rinse dry deposition particles from the leaf surfaces.
Rain collection systems should be designed to collect precipitation on an event basis and to
collect sequential samples during the event.
Two automated systems have recently been used. The Sangamo Precipitation Collector,
Type A, collects rain in a single bucket exposed at the beginning of the rain event (Samant
and Vaidya, 1982). A second sampler, described by Coscio et al. (1982), also remains covered
between rain events; it can collect a sequence of eight samples during the period of rain and
may be fitted with a refrigeration unit for sample cooling.
Because the physicochemical form of lead often influences environmental effects, there is
a need to differentiate among the various chemical forms. Complete differentiation among all
such forms is a complex task that has not yet been fully accomplished. The most commonly used
approach is to distinguish between dissolved and suspended forms of lead. All lead passing
through a 0.45 urn membrane filter is operationally defined as dissolved, while that retained
on the filter is defined as suspended (Kopp and McKee, 1979).
Containers used for sample collection and storage should be fabricated from essentially
fik
lead-free plastic or glass, e.g., conventional polyethylene, Teflon , or quartz. These con-
tainers must be leached with hot acid for several days to ensure minimum lead contamination
(Patterson and Settle, 1976).
The distance from emission sources and depth gradients associated with lead in soil must
be considered in designing the sampling plan. Vegetation, litter, and large objects such as
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stones should not be included in the sample. Depth samples should be collected at not greater
than 2 cm intervals to preserve vertical integrity.
Because most soil lead is in chemical forms unavailable to plants, and because lead is
not easily transported by plants, roots typically contain very little lead and shoots even
less. Before analysis, a decision must be made as to whether or not the plant leaf material
should be washed to remove surface contamination from dry deposition and soil particles. If
the plants are sampled for total lead content (e.g., if they serve as animal food sources),
they cannot be washed; if the effect of lead on internal plant processes is being studied, the
plant samples should be washed. In either case, the decision must be made at the time of sam-
pling, as washing cannot be effective after the plant materials have dried.
In sampling for airborne lead, air is drawn through filter materials such as glass fiber,
cellulose acetate, or porous plastic. These materials often include contaminant lead that can
interfere with the subsequent analysis. Procedures for cleaning filters to reduce the lead
blank rely on washing with acids or complexing agents. The type of filter and the analytical
method to be used often determines the ashing technique. In some methods, e.g., X-ray fluo-
rescence, analysis can be performed directly on the filter if the filter material is suitable.
Skogerboe (1974) provided a general review of filter materials.
The main advantages of glass fiber filters are low pressure drop and high particle col-
lection efficiency at high flow rates. The main disadvantage is variability in the lead blank,
which makes their use inadvisable in many cases. This has placed a high priority on the stan-
dardization of a suitable filter for hi-vol samples. Other investigations have indicated,
however, that glass fiber filters are now available that do not present a lead interference
A
problem (Scott et al., 1976b). Teflon filters have been used since 1975 by Dzubay et al.
(1982) and Stevens et al. (1978), who have shown these filters to have very low lead blanks
(<2 ng/cm2). The collection efficiencies of filters, and also of impactors, have been shown
to be dominant factors in the quality of the derived data.
1.4.2 Analytical Procedures
The choice of analytical method depends on the nature of the data required, the type of
sample being analyzed, the skill of the analyst, and the equipment available. For general
determination of elemental lead, atomic absorption spectroscopy (AAS) is widely used and re-
commended (C.F.R., 1982 40: § 50). Optical emission spectrometry and X-ray fluorescence
(XRF) are rapid and inexpensive methods for multielemental analyses. X-ray fluorescence can
measure lead concentrations reliably to 1 ng/m3 using samples collected with commercial
dichotomous samplers. Other analytical methods have specific advantages appropriate for
special studies,
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With respect to measuring lead without contamination during sampling or from the labora-
tory, several investigators have shown that the magnitude of the problem is quite large. It
appears that the problem may be caused by failure to control the blank or by failure to stan-
dardize instrument operation (Patterson, 1983; Skogerboe, 1982). The laboratory atmosphere,
collecting containers, and the labware used may be primary contributors to the lead blank
problem (Patterson, 1983; Skogerboe, 1982). Failure to recognize these and other sources of
contamination such as reagents and hand contact is very likely to result in the generation of
artificially high analytical results. Samples with less than 100 ng lead should be analyzed
in a clean laboratory especially designed for the elimination of lead contamination. Moody
(1982) has described the construction and application of such a laboratory at the National
Bureau of Standards.
For AAS, the lead atoms in the sample must be vaporized either in a precisely controlled
flame or in a furnace. Furnace systems in AAS offer high sensitivity as well as the ability
to analyze small samples. These enhanced capabilities are offset in part by greater dif-
ficulty in analytical calibration and by loss of analytical precision.
Particles may also be collected on cellulose acetate filters. Disks (0.5 cm2) are
punched from these filters and analyzed by insertion of nichrome cups containing the disks
into a flame. Another application involves the use of graphite cups as particle filters with
the subsequent analysis of the cups directly in the furnace system. These two procedures
offer the ability to determine particulate lead directly with minimal sample handling.
In an analysis using AAS and hi-vol samplers, atmospheric concentrations of lead were
found to be 0.076 ng/m3 at the South Pole (Maenhaut et al., 1979). Lead analyses of 995 par-
ticulate samples from the NASN were accomplished by AAS with an indicated precision of 11 per-
cent (Scott et al., 1976a). More specialized AAS methods for the determination of tetraalkyl
lead compounds in water and fish tissue have been described by Chau et al. (1979) and in air
by Birnie and Noden (1980) and Rohbock et al. (1980).
Techniques for AAS are still evolving. An alternative to the graphite furnace, evaluated
by Jin and Taga (1982), uses a heated quartz tube through which the metal ion in gaseous
hydride form flows continuously. Sensitivities were 1 to 3 ng/g for lead. The technique is
similar to the hydride generators used for mercury, arsenic, and selenium. Other nonflame
atomization systems, electrodeless discharge lamps, and other equipment refinements and tech-
nique developments have been reported (Horlick, 1982).
Optical emission spectroscopy is based on the measurement of the light emitted by
elements when they are excited in an appropriate energy medium. The technique has been used
to determine the lead content of soils, rocks, and minerals at the 5 to 10 ug/g level with a
relative standard deviation of 5 to 10 percent; this method has also been applied to the ana-
lysis of a large number of air samples (Sugimae and Skogerboe, 1978). The primary advantage
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of this method is that it allows simultaneous measurement of a large number of elements in a
small sample. In a study of environmental contamination by automotive lead, sampling times
were shortened by using a sampling technique in which lead-free porous graphite was used both
as the filter medium and as the electrode in the spectrometer. Lead concentrations of 1 to
10 ug/m3 were detected after a half-hour flow at 800 to 1200 ml/min through the filter.
More recent activities have focused attention on the inductively coupled plasma (ICP)
system as a valuable means of excitation and analysis (Garbarino and Taylor, 1979). The ICP
system offers a higher degree of sensitivity with less analytical interference than is typical
of many of the other emission spectroscopic systems. Optical emission methods are inefficient
when used for analysis of a single element, since the equipment is expensive and a high level
of operator training is required. This problem is largely offset when analysis for several
elements is required, as is often the case for atmospheric aerosols. X-ray fluorescence (XF)
allows simultaneous identification of several elements, including lead, using a high-energy
irradiation source. With the X-ray tubes coupled with fluorescers, very little energy is
transmitted to the sample; thus sample degradation is kept to a minimum. Electron beams and
radioactive isotope sources have been used extensively as energy sources for XRF analysis.
X-ray emission induced by charged-particle excitation (proton-induced X-ray emission or
PIXE) offers an attractive alternative to the more common techniques. The excellent capabi-
lity of accelerator beams for X-ray emission analysis is partially due to the relatively low
background radiation associated with the excitation.
X-radiation is the basis of the electron microprobe method of analysis. When an intense
electron beam is incident on a sample, it produces several forms of radiation, including
X-rays, whose wavelengths depend on the elements present in the material and whose intensities
depend on the relative quantities of these elements. The method is unique in providing com-
positional information on individual lead particles, thus permitting the study of dynamic che-
mical changes and perhaps allowing improved source identification.
Isotope dilution mass spectrometry (IDMS) is the most accurate measurement technique
known at the present time. No other techniques serve more reliably as a comparative refer-
ence; it has been used for analyses of subnanogram concentrations of lead in a variety of sam-
ple types (Chow et al., 1969, 1974; Facchetti and Geiss, 1982; Hirao and Patterson, 1974;
Murozumi et al., 1969; Patterson et al., 1976; Rabinowitz et al., 1973). The isotopic compo-
sition of lead peculiar to various ore bodies and crustal sources may also be used as a means
of tracing the origin of anthropogenic lead.
Colorimetric or spectrophotometric analysis for lead using dithizone (diphenylthiocarba-
zone) as the reagent has been used for many years. It was the primary method recommended by a
National Academy of Sciences (1972) report on lead, and the basis for the tentative method of
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testing for lead in the atmosphere by the American Society for Testing Materials (1975b).
Prior to the development of the IDMS method, colorimetric analysis served as the reference by
which other methods were tested.
Analytical methods based on electrochemical phenomena are found in a variety of forms.
They are characterized by a high degree of sensitivity, selectivity, and accuracy derived from
the relationship between current, charge, potential, and time for electrolytic reactions in
solutions. Anodic stripping voltammetry (ASV) is a two step process in which the lead is pre-
concentrated onto a mercury electrode by an extended but selected period of reduction. After
the reduction step, the potential is scanned either linearly or by differential pulse to oxi-
dize the lead and allow measurement of the oxidation (stripping) current.
The majority of analytical methods are restricted to measurement of total lead and cannot
directly identify the various compounds of lead. Gas chromatography (GC) using the electron
capture detector has been demonstrated to be useful for organolead compounds. The use of
atomic absorption as the GC detector for organolead compounds has been described by De Jonghe
et al. (1981), while a plasma emission detector has been used by Estes et al. (1981). In ad-
dition, Messman and Rains (1981) have used liquid chromatography with an atomic absorption
detector to measure organolead compounds. Mass spectrometry may also be used with gas chroma-
tography (Mykytiuk et al., 1980).
1.5 SOURCES AND EMISSIONS
The history of global lead emissions has been assembled from chronological records of de-
position in polar snow strata, marine and freshwater sediments, and the annual rings of trees.
These records aid in establishing natural background levels of lead in air, soils, plants,
animals, and humans, and they document the sudden increase in atmospheric lead at the time of
the industrial revolution, with a later burst during the 1920's when lead-alkyls were first
added to gasoline. Pond sediment analyses have shown a 20-fold increase in lead deposition
during the last 150 years (Figure 1-4), documenting not only the increasing use of lead since
the beginning of the industrial revolution in western United States, but also the relative
fraction of natural vs. anthropogenic lead inputs. Other studies have shown the same magni-
tude of increasing deposition in freshwater marine sediments. The pond and marine sediments
also document the shift in isotopic composition of atmospheric caused by increased commercial
use of the New Lead Belt in Missouri, where the ore body has an isotopic composition substan-
tially different from other ore bodies of the world.
Perhaps the best chronological record is that of the polar ice strata of Murozumi et al.
(1969), which extends nearly three thousand years back in time (Figure 1-4). At the South
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1750
1775
1950
1975
Figure 1-4. Chronological record of the relative increase of lead in snow strata, pond
and lake sediments, marine sediments, and tree rings. The data are expressed as a
ratio of the latest year of the record and should not be interpreted to extend back in
time to natural or uncontaminated levels of lead concentration.
Source: Adapted from Murozumi et al. (1969) (O), Shirahata et al. (1980) (D), Edgington
and Robbins (1976) (A), Ng and Patterson (1982) ( A), and Rolfe (1974) (• ).
Pole, Boutron (1982) observed a 4-fold Increase of lead in snow from 1957 to 1977 but saw no
Increase during the period 1927 to 1957. The author suggested the extensive atmospheric lead
pollution which began in the 1920's did not reach the South Pole until the mid-1950's. This
interpretation agrees with that of Maenhaut et al. (1979), who found atmospheric concentra-
tions of lead of 0.000076 M9/n>3 at the same location. This concentration is about 3-fold
higher than the 0.000024 ug/m3 estimated by Patterson (1980) and Servant (1982) to be the
natural lead concentration in the atmosphere. In summary, it is likely that atmospheric lead
emissions have increased 2000-fold since the pre-Roman era, that even at this early time the
atmosphere may have been contaminated by a factor of three over natural levels (Murozumi et
al. 1969), and that global atmospheric concentrations have increased dramatically since the
1920's.
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The history of global emissions may also be inferred from total production of lead.
The historical picture of lead production has been pieced together from many sources by Settle
and Patterson (1980) (Figure 1-5). Until the industrial revolution, lead production was
determined largely by the ability or desire to mine lead for its silver content. Since that
time, lead has been used as an industrial product in its own right, and efforts to improve
smelter efficiency, including control of stack emissions and fugitive dusts, have made lead
production more economical. This improved efficiency is not reflected in the chronological
record because of atmospheric emissions of lead from many other anthropogenic sources,
especially gasoline combustion (see Section 5.3.3). From this knowledge of the chronological
record, it is possible to sort out contemporary anthropogenic emissions from natural sources
of atmospheric lead.
8
c
OL
10*
10'
111
a
i 10*
Q
ec
o
z 10'
o
10'
10°
I I I I
SPANISH PRODUCTION
OF SILVER
IN NEW WORLD
EXHAUSTION
OF ROMAN
LEAD MINES
INDUSTRIAL
REVOLUTION
SILVER
PRODUCTION
IN GERMANY
DISCOVERY OF
CUPELLATION
I
INTRODUCTION
OF COINAGE
RISE AND FALL
OF ATHENS
ROMAN REPUBLIC
AND EMPIRE
\
I I
I
5500 5000 4500 4000 3500 3000 2500 2000 1500 1000 500 0
YEARS BEFORE PRESENT
Figure 1-5. The global lead production has changed historically in response to
major economic and political events. Increases in lead production (note log
scale) correspond approximately to historical increases in lead emissions shown
in Figure 5-1.
Source: Adapted from Settle and Patterson (1980).
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Lead enters the biosphere from lead-bearing minerals in the lithosphere through both
natural and man-made processes. Measurements of soil materials taken at 20-cm depths in the
continental United States show a median lead concentration of 15 to 16 |jg Pb/g soil. In
natural processes, lead is first incorporated in soil in the active root zone, from which it
may be absorbed by plants, leached into surface waters, or eroded into windborne dusts.
Calculations of natural contributions using geochemical information indicate that natural
sources contribute a relatively small amount of lead to the atmosphere. It has been estimated
from geochemical evidence that the natural particulate lead level is less than 0.0005 ug/m3
(National Academy of Sciences, 1980), and probably lower than the 0.000076 ug/m3 measured at
the South Pole (Maenhaut et al., 1979). In contrast, average lead concentrations in urban
suspended particulate matter range as high as 6 ug/m3 (U.S. Environmental Protection Agency,
1979, 1978). Evidently, most of this urban particulate lead originates from man-made sources.
Lead occupies an important position in the U.S. economy, ranking fifth among all metals
in tonnage used. Approximately 85 percent of the primary lead produced in this country is
from native mines, although often associated with minor amounts of zinc, cadmium, copper,
bismuth, gold, silver, and other minerals (U.S. Bureau of Mines, 1972-1982). Missouri lead
ore deposits account for approximately 80 to 90 percent of the domestic production. Total
utilization averaged approximately 1.36x10 t/yr over the 10-year period, with storage bat-
teries and gasoline additives accounting for ~70 percent of total use. Certain products,
especially batteries, cables, plumbing, weights, and ballast, contain lead that is
economically recoverable as secondary lead. Lead in pigments, gasoline additives, ammunition,
foil, solder, and steel products is widely dispersed and therefore is largely unrecoverable.
Approximately 40-50 percent of annual lead production is recovered and eventually recycled.
Lead or its compounds may enter the environment at any point during mining, smelting,
processing, use, recycling, or disposal. Estimates of the dispersal of lead emissions into
the environment by principal sources indicate that the atmosphere is the major initial
recipient. Estimated lead emissions to the atmosphere are shown in Table 1-1. Mobile and
stationary sources of lead emissions, although found throughout the nation, tend to be con-
centrated in areas of high population density, and near smelters. Figure 1-6 shows the ap-
proximate locations of major lead mines, primary and secondary smelters and refineries, and
alkyl lead paints (International Lead Zinc Research Organization, 1982).
The majority of lead compounds found in the atmosphere result from leaded gasoline com-
bustion. Several reports indicate that transportation sources contribute over 80 percent of
the total atmospheric lead. Other mobile sources, including aviation use of leaded gasoline
and diesel and jet fuel combustion, contribute insignificant lead emissions to the atmosphere.
Automotive lead emissions occur as PbBrCl in fresh exhaust particles. The fate of emit-
ted lead particles depends upon particle size. Particles initially formed by condensation of
SUMPB/0 1-16 9/30/83
-------
PRELIMINARY DRAFT
TABLE 1-1. ESTIMATED ATMOSPHERIC LEAD EMISSIONS FOR THE
UNITED STATES, 1981 AND THE WORLD
Source Category
Gasoline combustion
Waste oil combustion
Solid waste disposal
Coal combustion
Oil combustion
Wood combustion
Gray iron production
Iron and steel production
Secondary lead smelting
Primary copper smelting
Ore crushing and grinding
Primary lead smelting
Other metallurgical
Zn smelting
Ni smelting
Lead alkyl manufacture
Type metal
Portland cement production
Miscellaneous
Total
Annual
U.S.
Emissions
(t/yr)
35,000
830
319
950
226
--
295
533
631
30
326
921
54
245
85
71
233
40,739a
Percentage of
U.S. Total
Emissions
85.9
2.0
0.8
2.3
0.6
--
0.7V
1.3
1.5
0.1
0.8
2.3
0.1
0.6
0.2
0.2
0.5
100%
Annual
Global
Emissions
(t/yr)
273,000
8,900
14,000
6,000
4,500
50,000
770
27,000
8,200
31,000
16,000
2,500
7,400
5,900
449,170
Inventory does not include emissions from exhausting workroom air, burning of lead-painted
surfaces, welding of lead-painted steel structures, or weathering of painted surfaces.
Source: For U.S. emissions, Battye (1983); for global emissions, Nriagu (1979).
lead compounds in the combustion gases are quite small (well under 0.1 urn in diameter). Parti-
cles in this size category are subject to growth by coagulation and, when airborne, can remain
suspended in the atmosphere for 7 to 30 days and travel thousands of miles from their original
source. Larger particles are formed as the result of agglomeration of smaller condensation
particles and have limited atmospheric lifetimes.
During the lifetime of the vehicle, approximately 35 percent of the lead contained in the
gasoline burned by the vehicle will be emitted as small particles [<0.25 um mass median
equivalent diameter (MMED)], and approximately 40 percent will be emitted as larger particles
SUMPB/D
1-17
9/30/83
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I
I—•
oo
-o
73
MINES
A SMELTERS AND REFINERIES (7) '~
O SECONDARY SMELTERS AND REFINERIES (56)
• LEAD ALKYL PLANTS (4)
Figure 1-6. Locations of major lead operations in the United States.
Source: International Lead Zinc Research Organization (1982).
-------
PRELIMINARY DRAFT
(>10 |jm MMED) (Ter Haar et al., 1972). The remainder of the lead consumed in gasoline combus-
tion is deposited in the engine and exhaust system.
Although the majority (>90 percent on a mass basis) of vehicular lead compounds are emit-
ted as inorganic particles (e.g., PbBrCl), some organolead vapors (e.g., lead alkyls) are also
emitted. The largest volume of organolead vapors arises from the manufacture, transport, and
handling of leaded gasoline. Such vapors are photoreactive, and their presence in local atmo-
spheres is transitory. Organolead vapors are most likely to occur in occupational settings
and have been found to contribute less than 10 percent of the total lead present in the atmo-
sphere.
The use of lead additives in gasoline, which increased in volume for many years, is now
decreasing as automobiles designed to use unleaded fuel constitute the major portion of the
automotive population. The decline in the use of leaded fuel is the result of two regulations
promulgated by the U.S. Environmental Protection Agency (F.R., 1973 December 6). The first
required the availability of unleaded fuel for use in automobiles designed to meet federal
emission standards with lead-sensitive emission control devices (e.g., catalytic converters);
the second required a reduction or phase-down of the lead content in leaded gasoline. Compli-
ance with the phase-down of lead in gasoline has recently been the subject of proposed rule-
makings. The final action (F.R., 1982 October 29) replaced the present 0.5 g/gal standard for
the average lead content of all gasoline with a two-tiered standard for the lead content of
leaded gasoline. Under this proposed rule, refineries would be required to meet a standard of
1.10 g/gal for leaded gasoline while maintaining an average 0.5 g/gal for all gasoline.
The trend in lead content for U.S. gasolines is shown in Figure 1-7. Of the total gas-
oline pool, which includes both leaded and unleaded fuels, the average lead content has
decreased 63 percent, from an average of 1.62 g/gal in 1975 to 0.60 g/gal in 1981.
Data describing the lead consumed in gasoline and average ambient lead levels (composite
of maximum quarterly values) versus calendar year are plotted in Figure 1-8. The linear cor-
relation between lead consumed in gasoline and the composite maximum average quarterly ambient
average lead level is very good. Between 1975 and 1980, the lead consumed in gasoline
decreased 52 percent (from 165,577 metric tons to 78,679 metric tons) while the corresponding
composite maximum quarterly average of ambient lead decreased 51 percent (from 1.23 ug/m3 to
0.60 ug/m3). This indicates that control of lead in gasoline over the past several years has
effected a direct decrease in peak ambient lead concentrations.
Furthermore, the equation in Figure 1-8 implies that the complete elimination of lead
from gasoline might reduce the composite average of the maximum quarterly lead concentrations
at these stations to 0.05 ug/m3, a level typical of concentrations reported for nonurban sta-
tions in the U.S.
SUMPB/D 1-19 9/30/83
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PRELIMINARY DRAFT
2.40
2.00
s.
o>
1.50
(9
(0
3
o
111
OC
LU
1.00
0.50
0.00
LEADED FUEL
SALES WEIGHTED TOTAL
GASOLINE POOL
(LEADED AND UNLEADED
"AVERAGE")
UNLEADED FUEL
t t t' t t t
1975 1976 1977 1978 1979 1980 1981 1982*
CALENDAR YEAR
Figure 1-7. Trend in lead content of U.S. gasolines, 1975-1982. (DuPont, 1982).
•1982 DATA ARE FORECASTS.
SUMPB/D
1-20
9/30/83
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PRELIMINARY DRAFT
180
160
140
M
o
5 100
8
S 80
M
O
60
40
20
I
AVERAGE Pb - 6.93 x 106 (Pb CONSUMED) + 0.05
r2 = 0.99
1976
1977 (
'•1975
H978
19791
,•1980
1982*
I
I
I
I
I
I
0.20 0.40 0.60 0.80 1.00 1.20
COMPOSITE MAXIMUM QUARTERLY AVERAGE LEAD LEVELS, pglm3
Figure 1-8. Relationship between lead consumed in gasoline and composite maximum
quarterly average lead levels, 1975-1980.
•1981 AND 1982 DATA ARE ESTIMATES.
SUMPB/D
1-21
9/30/83
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PRELIMINARY DRAFT
Solid waste incineration and combustion of waste oil are principal contributors of lead
emissions from stationary sources. The manufacture of consumer products such as lead glass,
storage batteries, and lead additives for gasoline also contributes significantly to station-
ary source lead emissions. Since 1970, the quantity of lead emitted from the metallurgical
industry has decreased somewhat because of the application of control equipment and the clos-
ing of several plants, particularly in the zinc and pyrometallurgical industries.
A new locus for lead emissions emerged in the mid-1960s with the opening of the "Viburnum
Trend" or "New Lead Belt" in southeastern Missouri. The presence of ten mines and three ac-
companying lead smelters in this area makes it the largest lead-producing district in the
world.
There is no doubt that atmospheric lead has been a component of the human environment
since the earliest written record of civilization. Atmospheric emissions are recorded in
glacial ice strata and pond and lake sediments. The history of global emissions seems
closely tied to production of lead by industrially oriented civilizations. Although the
amount of lead to the atmosphere emitted from natural sources is a subject of controversy,
even the most liberal estimate (25 x 103 t/year) is dwarfed by the global emissions from
anthropogenic soujrces (450 X 103 t/year). The contribution of gasoline lead to total atmo-
spheric emissions has remained high, at 85 percent, as emissions from stationary sources have
decreased at the same pace as from mobile sources. The decrease in stationary source emis-
sions is due primarily to control of stack emissions, whereas the decrease in mobile source
emissions is a result of switchover to unleaded gasolines. Production of lead in the
United States has remained steady at about 1.2 X 106 t/year for the past decade. The gasoline
additive share of this market has dropped from 18 to 9.5 percent during the period 1971 to
1981. The decreasing use of lead in gasoline is projected to continue through 1990.
1.6 TRANSPORT AND TRANSFORMATION
At any particular location and time, the concentration of lead found in the atmosphere
depends on the proximity to the source, the amount of lead emitted from sources, and the de-
gree of mixing provided by the motion of the atmosphere. At the source, lead emissions are
typically around'10,000 ug/m3, while lead values in city air are usually between 0.1 and 10
ug/m3. These reduced concentrations are the result of dilution of effluent gas with clean air
and the removal of particles by wet or dry deposition. Characteristically, lead concentra-
tions are highest in confined areas close to sources and are progressively reduced by dilution
or deposition in districts more removed from sources. In parking garages or tunnels, atmo-
spheric lead concentrations can be ten to a thousand times greater than values measured near
roadways or in urban areas. In turn, atmospheric lead concentrations are usually about 2^
SUMPB/D 1-22 9/30/83
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PRELIMINARY DRAFT
times greater in the central city than in residential suburbs. Rural areas have even lower
concentrations. Particle size distribution stabilizes within a few hundred kilometers of the
sources, although atmospheric concentration continues to decrease with distance. Ambient
organolead concentrations decrease more rapidly than inorganic lead, suggesting conversion
from the organic to the inorganic phase during transport. Inorganic lead appears to convert
from lead halides and oxides to lead sulfates.
Lead is removed from the atmosphere by wet or dry deposition. The mechanisms of dry de-
position have been incorporated into models that estimate the flux of atmospheric lead to the
earth's surface. Of particular interest is deposition on vegetation surfaces, since this lead
may be incorporated into food chains. Between wet and dry deposition, it is possible to cal-
culate an atmospheric lead budget that balances the emission inputs with deposition outputs.
Particles in air streams are subject to the same principles of fluid mechanics as par-
ticles in flowing water. The first principle is that of diffusion along a concentration gra-
dient. If the airflow is steady and free of turbulence, the rate of mixing is determined by
the diffusivity of the pollutant. By making generalizations of windspeed, stability, and sur-
face roughness, it is possible to construct models using a variable transport factor called
eddy diffusivity (K), in which K varies in each direction, including vertically. There is a
family of K-theory models that describe the dispersion of particulate pollutants. The sim-
plest K-theory model produces a Gaussian plume, called such because the concentration of the
pollutant decreases according to a normal or Gaussian distribution in both the vertical and
horizontal directions. These models have some utility and are the basis for most of the air
quality simulations performed to date (Benarie, 1980). Another family of models is based on
the conservative volume element approach, where volumes of air are seen as discrete parcels
having conservative meteorological properties, (Benarie, 1980). The effect of pollutants on
these parcels is expressed as a mixing ratio. These parcels of air may be considered to move
along a trajectory that follows the advective wind direction. None of the models have been
tested for lead. All of the models require sampling periods of two hours or less in order for
the sample to conform to a well-defined set of meteorological conditions. In most cases, such
a sample would be below the detection limits for lead. The common pollutant used to test
models is SOp which can be measured over very short, nearly instantaneous, time periods. The
question of whether gaseous S02 can be used as a surrogate for particulate lead in these
models remains to be answered.
Dispersion not influenced by complex terrain features depends on emission rates and the
volume of clean air available for mixing. These factors are relatively easy to estimate and
some effort has been made to describe ambient lead concentrations which can result under
selected conditions. On an urban scale, the routes of transport can be inferred from an iso-
pleth, i.e., a plot connecting points of identical ambient concentrations. These plots always
show that lead concentrations are maximum where traffic density is highest.
SUMPB/D 1-23 9/30/83
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PRELIMINARY DRAFT
Dispersion beyond cities to regional and remote locations is complicated by the fact that
there are no monitoring network data from which to construct isopleths, that removal by
deposition plays a more important role with time and distance, and that emissions from many
different geographic locations sources converge. Dispersion from point sources such as
smelters and refineries is described with isopleths in the manner of urban dispersion,
although the available data are notably less abundant.
Trijonis et al. (1980) reported lead concentrations for seven sites in St. Louis,
Missouri. Values around the CBD are typically two to three times greater than those found in
the outlying suburbs in St. Louis County to the west of the city. The general picture is one
of peak concentrations within congested commercial districts which gradually decline in out-
lying areas. However, concentration gradients are not steep, and the whole urban area has
levels of lead above 0.5 (jg/m3. Lead in the air decreases 2Js-fold from maximum values in
center city areas to well populated suburbs, with a further 2-fold decrease in the outlying
areas. These modeling estimates are generally confirmed by measurement.
The 15 mines and 7 primary smelters and refineries shown in Figure 1-6 are not located in
urban areas. Most of the 56 secondary smelters and refineries are likewise non-urban. Con-
sequently, dispersion from these point sources should be considered separately, but in a man-
ner similar to the treatment of urban regions. In addition to lead concentrations in air,
concentrations in soil and on vegetation surfaces are often used to determine the extent of
dispersion away from smelters and refineries.
Beyond the immediate vicinity of urban areas and smelter sites, lead in air declines
rapidly to concentrations of 0.1 to 0.5 ug/m?. Two mechanisms responsible for this change are
dilution with clean air and removal by deposition.
Source reconciliation is based on the concept that each type of natural or anthropogenic
emission has a unique combination of elemental concentrations. Measurements of ambient air,
properly weighted during multivariate regression analysis, should reflect the relative amount
of pollutant derived from each of several sources (Stolzenberg et al., 1982). Sievering et
al. (1980) used the method of Stolzenberg et al. (1982) to analyze the transport of urban air
from Chicago over Lake Michigan. They found that 95 percent of the lead in Lake Michigan air
could be attributed to various anthropogenic sources, namely coal, fly ash, cement manufacture,
iron and steel manufacture, agricultural soil dust, construction soil dust, and incineration
emissions. Cass and McRae (1983) used source reconciliation in the Los Angeles Basin to
interpret 1976 NFAN data based on emission profiles from several sources. Their chemical ele-
ment balance model showed that 20 to 22 percent of the total suspended particle mass could be
attributed to highway sources.
Harrison and Williams (1982) determined air concentrations, particle size distributions,
and total deposition flux at one urban and two rural sites in England. The urban site, which
SUMPB/D 1-24 9/30/83
-------
PRELIMINARY DRAFT
had no apparent industrial, commercial or municipal emission sources, had an air lead concen-
tration of 3.8 ug/m3, whereas the two rural sites were about 0.15 ug/m3. The average particle
size became smaller toward the rural sites, as the MMED shifted downward from 0.5 urn to 0.1
urn.
Knowledge of lead concentrations in the oceans and glaciers provides some insight into
the degrees of atmospheric mixing and long range transport. Patterson and co-workers have
measured dissolved lead concentrations in sea water off the coast of California, in the
Central North Atlantic (near Bermuda), and in the Mediterranean. The profile obtained by
Schaule and Patterson (1980) is shown in Figure 1-9. Surface concentrations in the Pacific
(14 ng/kg) were found to be higher than those of the Mediterranean or the Atlantic, decreasing
abruptly with depth to a relatively constant level of 1 to 2 ng/kg. The vertical gradient was
found to be much less in the Atlantic. Below the mixing layer, there appears to be no differ-
ence between lead concentrations in the Atlantic and Pacific. These investigators calculated
that industrial lead currently is being added to the oceans at about 10 times the rate of in-
troduction by natural weathering, with significant amounts being removed from the atmosphere
by wet and dry deposition directly into the ocean. Their data suggest considerable contamina-
tion of surface waters near shore, diminishing toward the open ocean.
Investigations of trace metal concentrations (including lead) in the atmosphere in remote
northern and southern hemispheric sites have revealed that the natural sources for such atmos-
pheric trace metals include the oceans and the weathering of the earth's crust, while the
major anthropogenic source is particulate air pollution. Enrichment factors for concentra-
tions relative to standard values for the oceans and the crust were calculated; ninety percent
of the particulate pollutants in the global troposphere are injected in the northern hemi-
sphere (Robinson and Robbins, 1971). Since the residence times for particles in the tropo-
sphere are much less than the interhemispheric mixing time, it is unlikely that significant
amounts of particulate pollutants can migrate from the northern to the southern hemisphere via
the troposphere.
Murozumi et al. (1969) have shown that long range transport of lead particles emitted
from automobiles has significantly polluted the polar glaciers. They collected samples of
snow and ice from Greenland and the Antarctic (Figure 1-10). The authors attribute the gra-
dient increase after 1750 to the Industrial Revolution and the accelerated increase after 1940
to the increased use of lead alkyls in gasoline. The most recent levels found in the
Antarctic snows were, however, less than those found in Greenland by a factor of 10 or more.
Evidence from remote areas of the world suggests that lead and other fine particle com-
ponents are transported substantial distances, up to thousands of kilometers, by general
weather systems. The degree of surface contamination of remote areas with lead depends both
on weather influences and on the degree of air contamination. However, even in remote areas,
man's primitive activities can play an important role in atmospheric lead levels.
SUMPB/D 1-25 9/30/83
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PRELIMINARY DRAFT
I I I I I
1000
• DISSOLVED Pb
D PARTICULATE Pb
2 2000
$
I
i
Q 3000
4000
'/I
I I I I I I
5000
0 2 4 6 8 10 12 14 16 0
CONCENTRATION, ng Pb/kg
Figure 1-9. Profile of lead concentrations in the
central northeast Pacific. Values below 1000 m are
an order of magnitude tower than reported by
Tatsumoto and Patterson (1963) and Chow and
Patterson (1966).
Source: Schaule and Patterson (1980).
SUMPB/D
1-26
9/30/83
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PRELIMINARY DRAFT
0.20
0.18
0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
. . . I . . i . I . . . . I . . . . I .
800
k-B.c.-*+«-
1750
1800 1850
A. D.
1900
1950
AGE OF SAMPLES
Figure 1-10. Lead concentration profile in snow
strata of Northern Greenland.
Source: Murozumi et al. (1969).
Whitby et al. (1975) placed atmospheric particles into three different size regimes: the
nuclei mode (<0.1 urn), the accumulation mode (0.1 to 2 urn), and the large particle mode (>2
urn). At the source, lead particles are generally in the nuclei and large particle modes.
Large particles are removed by deposition close to the source and particles in the nuclei mode
diffuse to surfaces or agglomerate while airborne to form larger particles of the accumulation
mode. Thus it is in the accumulation mode that particles are dispersed great distances.
A number of studies have used gas absorbers behind filters to trap vapor-phase lead com-
pounds. Because it is not clear that all the lead captured in the backup traps is, in fact,
in the vapor phase in the atmosphere, "organic" or "vapor phase" lead is an operational
definition in these studies. Purdue et al. (1973) measured both particulate and organic lead
in atmospheric samples. They found that the vapor phase lead was about 5 percent of the total
lead in most samples. It is noteworthy, however, that in an underground garage, total lead
concentrations were approximately five times those in ambient urban atmospheres, and the
organic lead increased to approximately 17 percent.
Lead is emitted into the air from automobiles as lead halides and as double salts with
ammonium halides (e.g., PbBrCl • 2NH4C1). From mines and smelters, PbS04> PbO-PbS04, and PbS
appear to be the dominant species. In the atmosphere, lead is present mainly as the sulfate
SUMPB/D
1-27
9/30/83
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PRELIMINARY DRAFT
with minor amounts of halides. It is not completely clear just how the chemical composition
changes in transport.
The ratio of Br to Pb is often cited as an indication of automotive emissions. From the
mixtures commonly used in gasoline additives, the mass Br/Pb ratio should be about 0.386 if
there has been no fractionation of either element (Harrison and Sturges, 1983). However
several authors have reported loss of halide, preferentially bromine, from lead salts in atmo-
spheric transport. Both photochemical decomposition and acidic gas displacement have been
postulated as mechanisms. The Br/Pb ratios maybe only crude estimates of automobile emissions;
this ratio would decrease with distance from the highway from 0.39 to 0.35 at less proximate
sites and 0.25 in suburban residential areas. Habibi et al. (1970) studied the composition of
auto exhaust particles as a function of particle size. Their main conclusions follow:
1. Chemical composition of emitted exhaust particles is related to particle size.
2. There is considerably more soot and carbonaceous material associated with fine-
mode particles than with coarse-mode particles. Particulate matter emitted
under typical driving conditions is rich in carbonaceous material.
3. Only small quantities of 2PbBrCl-NH4Cl were found in samples collected at the
tailpipe from the hot exhaust gas. Lead-halogen molar ratios in particles of
less than 10 |jm MMED indicate that much more halogen is associated with these
solids than the amount expected from the presence of 2PbBrCl-NH^Cl.
Lead sulfide is the main constituent of samples associated with ore handling and fugitive
dust from open mounds of ore concentrate. The major constituents from sintering and blast
furnace operations appeared to be PbSO. and PbO-PbSO., respectively.
Before atmospheric lead can have any effect on organisms or ecosystems, it must be trans-
ferred from the air to a surface. For natural ground surfaces and vegetation, this process
may be either dry or wet deposition. Transfer by dry deposition requires that the particle
move from the main airstream through the boundary layer to a surface. The boundary layer is
defined as the region of minimal air flow immediately adjacent to that surface. The thickness
of the boundary layer depends mostly on the windspeed and roughness of the surface. Airborne
particles do not follow a smooth, straight path in the airstream. On the contrary, the path
of a particle may be affected by micro-turbulent air currents, gravitation, or its own iner-
tia. There are several mechanisms which alter the particle path sufficient to cause transfer
to a surface. These mechanisms are a function of particle size, windspeed, and surface char-
acteristics. Transfer from the main airstream to the boundary layer is usually by sedimenta-
tion or wind eddy diffusion. From the boundary layer to the surface, transfer may be by any
of the six mechanisms, although those which are independent of windspeed (sedimentation, in-
terception, Brownian diffusion) are more likely.
SUMPB/D 1-28 9/30/83
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PRELIMINARY DRAFT
Particles transported to a surface by any mechanism are said to have an effective de-
position velocity (V .) which is measured not by rate of particle movement but by accumulation
on a surface as a function of air concentration. Several recent models of dry deposition have
evolved from the theoretical discussion of Fuchs (1964) and the wind tunnel experiments of
Chamberlain (1966). The models of Slinn (1982) and Davidson et al. (19"82) are particularly
useful for lead deposition. SI inn's model considers a multitude of vegetation parameters to
find several approximate solutions for particles in the size range of 0.1 to 1.0 ^m, estima-
ting deposition velocities of 0.01 to 0.1 cm/sec. The model of Davidson et al. (1982) is
based on detailed vegetation measurements and wind data to predict a V. of 0.05 to 1.0 cm/sec.
Deposition velocities are specific for each vegetation type. Both models show a decrease in
deposition velocity as particle size decrease down to about 0.1 to 0.2 urn; as diameter
decreases further from 0.1 to 0.001 urn, deposition velocity increases (see Figure 6-1).
Several investigators have used surrogate surface devices to measure dry deposition
rates. The few studies available on deposition to vegetation surfaces show deposition rates
comparable to those of surrogate surfaces and deposition velocities in the range predicted by
the models discussed above (Table 1-2). These data show that global emissions are in approxi-
mate balance with global deposition.
Andren et al. (1975) evaluated the contribution of wet and dry deposition of lead in a
study of the Walker Branch Watershed in Oak Ridge, Tennessee, during the period June, 1973 -
July, 1974. The mean precipitation in the area is approximately 130 cm/yr. Wet deposition
contributed approximately 67 percent of the total deposition for the period.
The geochemical mass balance of lead in the atmosphere may be determined from quantita-
tive estimates of inputs and outputs. Inputs amount to 450,000 - 475,000 metric tons an-
nually (Table 1-1). The amount of lead removed by wet deposition is approximately 208,000
t/yr (Table 1-3).
The deposition flux for each vegetation type shown on Table 1-3 totals 202,000. The
combined wet and dry deposition is 410,000 metric tons, which compares favorably with the es-
timated 450,000 - 475,000 metric tons of emissions.
Soils have both a liquid and solid phase, and trace metals are normally distributed be-
tween these two phases. In the liquid phase, metals may exist as free ions or as soluble com-
plexes with organic or inorganic ligands. Organic ligands are typically humic substances such
as fulvic or humic acid, and the inorganic ligands may be iron or manganese hydrous oxides.
Since lead rarely occurs as a free ion in the liquid phase (Camerlynck and Kiekens, 1982), its
mobility in the soil solution depends on the availability of organic or inorganic ligands.
The liquid phase of soil often exists as a thin film of moisture in intimate contact with the
solid phase. The availability of metals to plants depends on the equilibrium between the
liquid and solid phase. In the solid phase, metals may be incorporated into crystalline
SUMPB/D 1-29 9/30/83
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PRELIMINARY DRAFT
TABLE 1-2. SUMMARY OF SURROGATE AND VEGETATION SURFACE DEPOSITION OF LEAD
Depositional Surface
Tree leaves (Paris)
Tree leaves (Tennessee)
Plastic disk (remote
California)
Plastic plates
Flux
ng Pb/cnvVday
0.38
0.29-1.2
0.02-0.08
0.29-1.5
Air Cone
ng/m?
—
—
13-31
110
Deposition Velocity
cm/sec
0.086
—
0.05-0.4
0.05-0.06
Reference
1
2
3
4
(Tennessee)
Tree leaves (Tennessee)
Snow (Greenland)
Grass (Pennsylvania)
Coniferous forest (Sweden)
—
0.004
—
0.74
110
0.1-0.2
590
21
0.005
0.1
0.2-1.1
0.41
4
5
6
7
1. Servant, 1975
2. Lindberg et al., 1982
3. Elias and Davidson, 1980
4. Lindberg and Harriss, 1981
5. Davidson et al., 1981C
6. Davidson et al., 1982
7. Lannefors et al., 1983
minerals of parent rock material and secondary clay minerals or precipitated as insoluble
organic or inorganic complexes. They may also be adsorbed onto the surfaces of any of these
solid forms. Of these categories, the most mobile form is in soil moisture, where lead can
move freely into plant roots or soil microorganisms with dissolved nutrients. The least
mobile is parent rock material, where lead may be bound within crystalline structures over
geologic periods of time; intermediate are the lead complexes and precipitates. Trans-
formation from one form to another depends on the chemical environment of the soil. The water
soluble and exchangeable forms of metals are generally considered available for plant uptake
(Camerlynck and Kiekens, 1982). These authors demonstrated that in normal soils, only a small
fraction of the total lead is in exchangeable form (about 1 |jg/g) and none exists as free lead
ions. Of the exchangeable lead, 30 percent existed as stable complexes, 70 percent as labile
complexes.
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TABLE 1-3. ESTIMATED GLOBAL DEPOSITION OF ATMOSPHERIC LEAD
Deposition from Atmosphere
Mass Concentration Deposition
1017 kg/yr 10-* g/kg 10? kg/yr
Wet
To oceans
To continents
Dry
4.1
1.1
Area
10l!f km?
To oceans, ice caps, deserts 405
Grassland, agricultural
0.4
0.4
Deposition rate
10-? g/mVyr
0.2
164
44
Deposition
106 kg/yr
89
areas, and tundra 46 0.71
Forests 59 1.5
Total dry:
Total wet:
Global:
33
80
202
208
410
Source: This report.
Atmospheric lead may enter the soil system by wet or dry deposition mechanisms. Lead
could be immobilized by precipitation as less soluble compounds [PbCO,, Pb(P04)23, by ion ex-
change with hydrous oxides or clays, or by chelation with humic and fulvic acids. Lead im-
mobilization is more strongly correlated with organic chelation than with iron and managanese
oxide formation (Zimdahl and Skogerboe, 1977). If organic chelation is the correct model of
lead immobilization in soil, then several features of this model merit further discussion.
First, the total capacity of soil to immobilize lead can be predicted from the linear rela-
tionship developed by Zimdahl and Skogerboe (1977) (Figure 1-11) based on the equation:
N = 2.8 x 10"6 (A)
1.1 x 10"5 (B) - 4.9 x 10"5
where N is the saturation capacity of the soil expressed in moles/g soil, A is the cation ex-
change capacity of the soil in meq/100 g soil, and B is the pH.
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The soil humus model also facilitates the calculation of lead in soil moisture using
values available in the literature for conditional stability constants (K) with fulvic acid.
The values reported for log K are linear in the pH range of 3 to 6 so that interpolations in
the critical range of pH 4 to 5.5 are possible (Figure 1-11). Thus, at pH 4.5, the ratio of
complexed lead to ionic lead is expected to be 3.8 x 103. For soils of 100 ug/g, the ionic
lead in soil moisture solution would be 0.03 ug/g.
5.0
x
in
_
o
E
z
o
c
1
pH = 8
pH = 6
pH = 4
< 2.0 -
50 75
CEC, meq/100 g
100
12S
Figure 1-11. Variation of lead saturation capacity with cation exchange
capacity in soil at selected pH values.
Source: Data from Zimdahl and Skogerboe (1977).
It is also important to consider the stability constant of the Pb-FA complex relative to
other metals. Schnitzer and Hansen (1970) showed that at pH 3, Fe3 is the most stable in
the sequence Fe3* > Al3* > Cu2* > Ni 2* > Co2* > Pb2* > Ca2* > Zn2* > Mn2* > Mg2*. At PH
5, this sequence becomes Ni2* = Co2* > Pb2* > Cu2* > Zn2* = Mn2* > Ca2* > Mg2*. This
means that at normal soil pH levels of 4.5 to 8, lead is bound to FA + HA in preference to
many other metals that are known plant nutrients (Zn, Mn, Ca, and Mg).
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Lead does not pass easily to ground or surface water. Any lead dissolved from primary
lead sulfide ore tends to combine with carbonate or sulfate ions to form insoluble lead car-
bonate or lead sulfate, or be absorbed by ferric hydroxide. An outstanding characteristic of
lead is its tendency to form compounds of low solubility with the major anions of natural
water. The hydroxide, carbonate, sulfide, and more rarely the sulfate may act as solubility
controls in precipitating lead from water. The amount of lead that can remain in solution is
a function of the pH of the water and the dissolved salt content. A significant fraction of
the lead carried by river water may be in an undissolved state. This insoluble lead can con-
sist of colloidal particles in suspension or larger undissolved particles of lead carbonate,
-oxide, -hydroxide, or other lead compounds incorporated in other components of particulate
lead from runoff; it may occur either as sorbed ions or surface coatings on sediment mineral
particles or be carried as a part of suspended living or nonliving organic matter.
The bulk of organic compounds in surface waters originates from natural sources.
(Neubecker and Allen, 1983). The humic and fulvic acids that are primary complexing agents in
soils are also found in surface waters at concentrations from 1 to 5 mg/1, occasionally ex-
ceeding 10 mg/1. The presence of fulvic acid in water has been shown to increase the rate of
solution of lead sulfide 10 to 60 times over that of a water solution at the same pH that did
not contain fulvic acid. At pH values near 7, soluble lead-fulvic acid complexes are present
in solution.
The transformation of inorganic lead, especially in sediment, to tetramethyllead (TML)
has been observed and biomethylation has been postulated. However, Reisinger et al. (1981)
have reported extensive studies of the methylation of lead in the presence of numerous
bacterial species known to alkylate mercury and other heavy metals. In these experiments no
biological methylation of lead was found under any condition.
Lead occurs in riverine and estuarial waters and alluvial deposits. Concentrations of
lead in ground water appear to decrease logarithmically with distance from a roadway. Rain-
water runoff has been found to be an important transport mechanism in the removal of lead from
a roadway surface in a number of studies. Apparently, only a light rainfall, 2 to 3 mm, is
sufficient to remove 90 percent of the lead from the road surface to surrounding soil and to
waterways. The lead concentrations in off-shore sediments often show a marked increase
corresponding to anthropogenic activity in the region. An average anthropogenic flux of 72
mg/m2-yr, of which 27 mg/m2»yr could be attributed to direct atmospheric deposition. Prior to
1650, the total flux was 12 mg/m2-yr, so there has been a 6-fold increase since that time. Ng
and Patterson (1982) found prehistoric fluxes of 1 to 7 mg Pb/m2-yr to three offshore basins
in southern California, which have now increased 3 to 9-fold to 11 to 21 mg/m2-yr. Much of
this lead is deposited directly from sewage outfalls, although at least 25 percent probably
comes from the atmosphere.
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The deposition of lead on the leaf surfaces of plants where the particles are often re-
tained for a long time can be important. Several studies have shown that plants near roadways
exhibit considerably higher levels of lead than those farther away. Rainfall does not gene-
rally remove the deposited particles. Animals or humans consuming the leafy portions of such
plants can be exposed to higher than normal levels of lead. The particle deposition on leaves
has led some investigators to stipulate that lead may enter plants through the leaves. Arvik
and Zimdahl (1974) have shown that entry of ionic lead through plant leaves is of minimal
importance. Using the leaf cuticles of several types of plants essentially as dialysing mem-
branes, they found that even high concentrations of lead ions would not pass through the cuti-
cles into distilled water on the opposite side.
1.7 ENVIRONMENTAL CONCENTRATIONS AND POTENTIAL PATHWAYS TO HUMAN EXPOSURE
In general, typical levels of human lead exposure may be attributed to four components of
the human environment: inhaled air, dusts of various types, food and drinking water. A base-
line level of potential human exposure is determined for a normal adult eating a typical diet
and living in a non-urban community. This baseline exposure is deemed to be unavoidable by
any reasonable means. Beyond this level, additive exposure factors can be determined for
other environments (urban, occupational, smelter communities), for certain habits and activi-
ties (smoking, drinking, pica, and hobbies), and for variations due to age, sex, or socio-
economic status.
1.7.1 Lead in Air
Ambient airborne lead concentrations may influence human exposure through direct inhala-
tion of lead-containing particles and through ingestion of lead which has been deposited from
the air onto surfaces. Our understanding of the pathways to human exposure is far from com-
plete because most ambient measurements were not taken in conduction with studies of the con-
centrations of lead in man or in components of his food chain.
The most complete set of data on ambient air concentrations may be extracted from the
National Filter Analysis Network (NFAN) and its predecessors. In remote regions of the world,
air concentrations are two or three orders of magnitude lower than in urban areas, lending
credence to estimates of the concentrations of natural lead in the atmosphere. In the context
of this data base, the conditions which modify ambient air, as measured by the monitoring net-
works, to air inhaled by humans cause changes in particle size distributions, changes with
vertical distance above ground', and differences between indoor and outdoor concentrations.
The wide range of concentration is apparent from Table 1-4, which summarizes data ob-
tained from numerous independent measurements. Concentrations vary from 0.000076 ug/m3 in
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PRELIMINARY DRAFT
TABLE 1-4. ATMOSPHERIC LEAD IN URBAN, RURAL, AND REMOTE AREAS OF THE WORLD
Location Sampl
Urban
Miami
New York
Boston
St. Louis
Houston
Chicago
Salt Lake City
Los Angeles
Ottowa
Toronto
Montreal
Berlin
Vienna
Zurich
Brussels
Turin
Rome
Paris
Rio de Janeiro
Rural
New York Bight
Framingham, MA
Chadron, NE
United Kingdom
Italy
Belgium
Remote
White Mtn. , CA
High Sierra, CA
Olympic Nat. Park, WA
Antarctica
South Pole
Thule, Greenland
Thule, Greenland
Prins Christian-
sund, Greenland
Dye 3, Greenland
Eniwetok, Pacific Ocean
Kumjung, Nepal
Bermuda
Spitsbergen
ing Period
1974
1978-79
1978-79
1973
1978-79
1979
1974
1978-79
1975
1975
1975
1966-67
1970
1970
1978
1974-79
1972-73
1964
1972-73
1974
1972
1973-74
1972
1976-80
1978
1969-70
1976-77
1980
1971
1974
1965
1978-79
1978-79
1979
1979
1979
1973-75
1973-74
Lead cone, (pg/m3)
1.3
1.1
0.8
1.1
0.9
0.8
0.89
1.4
1.3
1.3
2.0
3.8
2.9
3.8
0.5
4.5
4.5
4.6
0.8
0.13
0.9
0.045
0.13
0.33
0.37
0.008
0.021
0.0022
0.0004
0.000076
0.0005
0.008
0.018
0.00015
0.00017
0.00086
0.0041
0.0058
Reference
HASL, 1975
see Table 7-3
see Table 7-3
see Table 7-3
see Table 7-3
see Table 7-3
HASL, 1975
see Table 7-3
NAPS, 1975
NAPS, 1975
NAPS, 1975
Blokker, 1972
Hartl and Resch, 1973
HSgger, 1973
Roels et al., 1980
Facchetti and Geiss, 1982
Colacino and Lavagnini, 1974
Blokker, 1972
Branquinho and Robinson, 1976
Duce et al. , 1975
O'Brien et al., 1975
Struempler, 1975
Cawse, 1974
Facchetti and Geiss , 1982
Roels et al. 1980
Chow et al . , 1972
Eli as and Davidson, 1980
Davidson et al. , 1982
Duce, 1972
Maenhaut et al . , 1979
Murozumi et al . , 1969
He id am, 1981
He i dam, 1981
Davidson et al. , 1981c
Settle and Patterson, 1982
Davidson et al., 1981b
Duce et al . , 1976
Larssen, 1977
JA11 references listed as cited in Nriagu (1978b).
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remote areas to over 10 ug/m3 near sources such as smelters. Many of the remote areas are far
from human habitation and therefore do not reflect human exposure. However, a few of the
regions characterized by small lead concentrations are populated by individuals with primitive
lifestyles; these data provide baseline airborne lead data to which modern American lead expo-
sures can be compared.
The remote area concentrations reported in Table 1-4 do not necessarily reflect natural,
preindustrial lead. Murozumi et al. (1969) and Ng and Patterson (1981) have measured a 200-
fold increase in the lead content of Greenland snow over the past 3000 years. The authors
state that this lead originates in populated mid-latitude regions, and is transported over
thousands of kilometers through the atmosphere to the Arctic. All of the concentrations in
Table 1-4, including values for remote areas, have been influenced by anthropogenic lead emis-
sions.
The data from the Air Filter networks show both the maximum quarterly average to reflect
compliance of the station to the ambient airborne standard (1.5 ug/m3), and quarterly aver-
ages to show trends at a particular location. The number of stations complying with the stan-
dard has increased, the quarterly averages have decreased, and the maximum 24-hour values ap-
pear to be smaller since 1977.
It seems likely that the concentration of natural lead in the atmosphere is between
0.00002 and 0.00007 ug/m3. A value of 0.00005 will be used for calculations regarding the
contribution of natural air lead to total human uptake.
The effect of the 1978 National Ambient Air Quality Standard for Lead has been to reduce
the air concentration of lead in major urban areas. Similar trends may also be seen in urban
areas of smaller population density. There are many factors which can cause differences
between the concentration of lead measured at a monitoring station and the actual inhalation
of air by humans. Air lead concentrations usually decrease with vertical and horizontal dis-
tance from emission sources, and are generally lower indoors than outdoors.
New guidelines for placing ambient air lead monitors went into effect in July, 1981
(F.R., 1981 September 3). "Microscale" sites, placed between 5 and 15 meters from thorough-
fares and 2 to 7 meters above the ground, are prescribed, but until now few monitors have been
located that close to heavily travelled roadways. Many of these microscale sites might be ex-
pected to show higher lead concentrations than measured at nearby middlescale urban sites, due
complex. Our understanding of the complex factors affecting the vertical distribution of air-
borne lead is extremely limited, but the data indicate that air lead concentrations are pri-
marily a function of distance from the source, whether vertical or horizontal.
Because people spend much of their time indoors, ambient air data may not accurately
indicate actual exposure to airborne lead. Some studies show smaller indoor/outdoor ratios
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during the winter, when windows and doors are tightly closed. Overall, the data suggest
indoor/outdoor ratios of 0.6-0.8 are typical for airborne lead in houses without air con-
ditioning. Ratios in air conditioned houses are expected to be in the range of 0.3-0.5
(Yocum, 1982). Even detailed knowledge of indoor and outdoor airborne lead concentrations at
fixed locations may still be insufficient to assess human exposure to airborne lead. The
study of Tosteson et al. (1982) included measurement of airborne lead concentrations using
personal exposure monitors, carried by individuals going about their day-to-day activities.
In contrast to the lead concentrations of 0.092 and 0.12 pg/m3 at fixed locations, the average
personal exposure was 0.16 pg/rn3. The authors suggest the inadequacy of using fixed monitors
at either indoor or outdoor locations to assess exposure.
Much of the lead in the atmosphere is transferred to terrestrial surfaces where it is
eventually passed to the upper layer of the soil surface. Crustal lead concentrations in soil
range from less than 10 to greater than 70 ug/g. The range of values probably represent
natural levels of lead in soil, although there may have been some contamination with anthro-
pogenic lead during collection and handling.
1.7.2 Lead in Soil and Dust
Studies have determined that atmospheric lead is retained in the upper two centimeters of
undisturbed soil, especially soils with at least 5 percent organic matter and a pH of 5 or
above. There has been no general survey of this upper 2 cm of the soil surface in the United
States, but several studies of lead in soil near roadsides and smelters and a few studies of
lead in soil near old houses with lead-based paint can provide the backgound information for
determining potential human exposures to lead from soil. Because lead is immobilized by the
organic component of soil, the concentration of anthropogenic lead in the upper 2 cm is deter-
mined by the flux of atmospheric lead to the soil surface. Near roadsides, this flux is
largely by dry deposition and the rate depends on particle size and concentration. In gen-
eral, deposition flux drops off abruptly with increasing distance from the roadway. This
effect is demonstrated in studies which show surface soil lead decreases exponentially up to
25 m from the edge of the road. Roadside soils may contain atmospheric lead from 30 to 2000
mg/g in excess of natural levels within 25 meters of the roadbed, all in the upper layer of
the soil profile.
Near primary and secondary smelters, lead in soil decreases exponentially within a 5-10
km zone around the smelter complex. Soil lead contamination varies with the smelter emission
rate, length of time the smelter has been in operation, prevailing windspeed and direction,
regional climatic conditions, and local topography.
Urban soils may be contaminated from a variety of atmospheric and non-atmospheric
sources. The major sources of soil lead seem to be paint chips from older houses and deposi-
tion from nearby highways. Lead in soil adjacent to a house decreases with distance; this may
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be due to paint chips or to dust of atmospheric origin washing from the rooftop (Wheeler and
Rolfe, 1979).
A definitive study which describes the source of soil lead was reported by Gulson et al.
(1981) for soils in the vicinity of Adelaide, South Australia. In an urban to rural transect,
stable lead isotopes were measured in the top 10 cm of soils over a 50 km distance. By their
isotopic compositions, three sources of lead were identified: natural, non-automotive in-
dustrial lead from Australia, and tetraethyl lead manufactured in the United States. The re-
sults indicated most of the soil surface lead originated from leaded gasoline. Lead may be
found in inorganic primary minerals, on humic substances, complexed with Fe-Mn oxide films, on
secondary minerals or in soil moisture. All of the lead in primary minerals is natural and is
bound tightly within the crystalline structure of the minerals. The lead on the surface of
these minerals is leached slowly into the soil moisture. Atmospheric lead forms complexes
with humic substances or on oxide films, that are in equilibrium with soil moisture, although
the equilibrium strongly favors the complexing agents. Except near roadsides and smelters,
only a few ug of atmospheric lead have been added to each gram of soil. Several studies in-
dicate that this lead is available to plants and that even with small amounts of atmospheric
lead, about 75 percent of the lead in soil moisture is of atmospheric origin.
Lead on the surfaces of vegetation may be of atmospheric origin. In internal tissues,
lead maybe a combination of atmospheric and soil origin. As with soils, lead on vegetation
surfaces decreases exponentially with distance away from roadsides and smelters. This de-
posited lead is persistent. It is neither washed off by rain nor taken up through the leaf
surface. Lead on the surface of leaves and bark is proportional to air lead concentrations
and particle size distributions. Lead in internal plant tissues is directly related to lead
in soil.
1.7.3 Lead in Food
In a study to determine the background concentrations of lead and other metals in agri-
cultural crops, the Food and Drug Administration (Wolnik et al., 1983), in cooperation with
the U.S. Department of Agriculture and the U.S. Environmental Protection Agency, analyzed over
1500 samples of "the most common crops taken from a cross section of geographic locations.
.Collection sites were remote from mobile or stationary sources of lead. Soil lead concentra-
tions were within the normal range (8-25 ug/g) of U.S. soils. The concentrations of lead in
crops are shown as "Total" concentrations on Table 1-5. The total concentration data should
probably be seen as representing the lowest concentrations of lead in food available to
Americans. The data on these ten crops suggest that root vegetables have lead concentrations
between 0.0046 and 0.009 ug/g, all soil lead. Aboveground parts not exposed to significant
amounts of atmospheric deposition (sweet corn and tomatoes) have less lead internally. If it
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PRELIMINARY DRAFT
is assumed that this same concentration is the internal concentration for aboveground parts
for other plants, it is apparent that five crops have direct atmospheric deposition in pro-
portion to surface area and estimated duration of exposure. The deposition rate of 0.04
ng/cm2-day in rural environments could account for these amounts of direct atmospheric lead.
TABLE 1-5. BACKGROUND LEAD IN BASIC FOOD CROPS AND MEATS
(ug/g fresh weight)
Crop
Wheat
Potatoes
Field corn
Sweet corn
Soybeans
Peanuts
Onions
Rice
Carrots
Tomatoes
Spinach
Lettuce
Beef (muscle)
Pork (muscle)
Natural
Pb
0.0015
0.0045
0.0015
0.0015
0.021'
0.050
0.0023
0.0015
0.0045
0.001
0.0015
0.0015
0. 0002
0.0002
Indirect
Atmospheric
0.0015
0.0045
0.0015
0.0015
0.021
0.050
0.0023
0.0015
0.0045
0.001
0.0015
0.0015
0.002
0.002
Direct
Atmospheric
0.034
—
0.019
—
--
—
—
0.004
—
—
0.042
0.010
0.02
0.06
Total f
0.037
0.009
0.022*
0.003
0.042
0.10Q
0.0046*
0.007*
0.009*
0.002*
0.045*
0.013
0.02**
0.06**
'except as indicated, data are from Wolnick et al. (1983)
*preliminary data provided by the Elemental Analysis Research Center, Food and Drug
Administration, Cincinnati, OH
**data from Penumarthy et al. (1980)
Lead in food crops varies according to exposure to the atmosphere and in proportion to the ef-
fort taken to separate husks, chaff, and hulls from edible parts during processing for human
or animal consumption. Root parts and protected aboveground parts contain natural lead and
indirect atmospheric lead, both derived from the soil. For exposed aboveground parts, any
lead in excess of the average of unexposed aboveground parts is considered to have been
directly deposited from the atmosphere.
1.7.4 Lead in Water
Lead occurs in untreated water in either dissolved or particulate form. Dissolved lead is
operationally defined as that which passes through a 0.45 urn membrane filter. Because atmos-
pheric lead in rain or snow is retained by soil, there is little correlation between lead in
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precipitation and lead in streams that drain terrestrial watersheds. Rather, the important
factors seem to be the chemistry of the stream (pH and hardness) and the volume of the stream
flow. For groundwater, chemistry is also important, as is the geochemical composition of the
water-bearing bedrock.
Streams and lakes are influenced by their water chemistry and the lead content of their
sediments. At neutral pH, lead moves from the dissolved to particulate form and the particles
eventually pass to sediments. At low pH, the reverse pathway is generally the case. Hard-
ness, which is a combination of the Ca and Mg concentration, can also influence lead concen-
trations. At higher concentrations of Ca and Mg, the solubility of lead decreases. Municipal
and private wells typically have a neutral pH and somewhat higher than average hardness. Lead
concentrations are not influenced by acid rain, surface runoff or atmospheric deposition.
Rather, the primary determinant of lead concentration is the geochemical makeup of the bedrock
that is the source of the water supply. Ground water typically ranges from 1 to 100 ug Pb/1
(National Academy of Sciences, 1980).
Whether from surface or ground water supplies, municipal waters undergo extensive chem-
ical treatment prior to release to the distribution system. Although there is no direct ef-
fort to remove lead from the water supply, some treatments, such as flocculation and sedimen-
tation, may inadvertently remove lead along with other undesirable substances. On the other
hand, chemical treatment to soften water increases the solubility of lead and enhances the
possibility that lead1 will be added to' water as it passes through the distribution system.
For samples taken at the household tap, lead concentrations are usually higher in the initial
volume (first daily flush) than after the tap has been running for some time. Water $tanding
in the pipes for several hours is intermediate between these two concentrations. (Sharrett et
al., 1982; Worth et al.. 1981).
1.7.5 Baseline Exposures to Lead
Lead concentrations in environmental media that are in the pathway to human consumption
are summarized on Table 1-6. Because natural lead is generally three to four orders of magni-
tude lower than anthropogenic lead in ambient rural or urban air, all atmospheric contri-
butions of lead are considered to be of anthropogenic origin. Natural soil lead typically
ranges from 10 to 30 ug/g, but much of this is tightly bound within the crystalline matrix of
soil minerals at normal soil pHs of 4 to 8. Lead in the organic fraction of soil is part
natural and part atmospheric. The fraction derived from fertilizer is considered to be
minimal. In undisturbed rural and remote soils, the ratio of natural to atmospheric lead is
about 1:1, perhaps as high as 1:3. This ratio persists through soil moisture and into in-
ternal plant tissues.
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TABLE 1-6. SUMMARY OF ENVIRONMENTAL CONCENTRATIONS OF LEAD
Medium
Air urban (ug/m3)
rural (ug/n»3)
Soil Total (ug/g)
Food Crops (H9/g)
Surface water (ug/g)
Ground water (ug/g)
Natural
Lead
0.00005
0.00005
8-25
0.0025
0.00002
0.003
Atmospheric
Lead
0.8
0.2
3.0
0.027
0.005
—
Total
Lead
0.8
0.2
15.0
0.03
0.005
0.003
In tracking air lead through pathways to human exposure, it is necessary to distinguish
between atmospheric lead that has passed through the soil, called indirect atmospheric here,
and atmospheric lead that has deposited directly on crops or water. Because indirect atmos-
pheric lead will remain in the soil for many decades, this source is insensitive to projected
changes in atmospheric lead concentrations.
Initially, a current baseline exposure scenario is described for an individual with a
minimum amount of daily lead consumption. This person would live and work in a nonurban en-
vironment, eat a normal diet of food taken from a typical grocery shelf, and would have no
habits or activities that would tend to increase lead exposure. Lead exposure at the baseline
level is considered unavoidable without further reductions of lead in the atmosphere or in
canned foods. Most of the baseline lead is of anthropogenic origin.
To arrive at a minimum or baseline exposure for humans, it is necessary to begin with the
environmental components, air, soil, food crops and water, that are the major sources of lead
consumed by humans (Table 1-6). These components are measured frequently, even monitored
routinely in the case of air, so that much data are available on their concentrations. But
there are several factors which modify these components prior to actual human exposure: We do
not breathe air as monitored at an atmospheric sampling station; we may be closer to or
farther from the source of lead than is the monitor; we may be inside a building, with or
without filtered air; water we drink does not come directly from a stream or river, but often
has passed through a chemical treatment plant and a distribution system. A similar type of
processing has modified the lead levels present in our food.
Besides the atmospheric lead in environmental components, there are two other industrial
components which contribute to this baseline of human exposure: paint pigments and lead
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solder. Solder contributes directly to the human diet through canned food and copper water
distribution systems. Paint and solder are also a source of lead-bearing dusts. The most
common dusts in the baseline human environment are street dusts and household dusts. They
originate as emissions from mobile or stationary sources, as the oxidation products of surface
exposure, or as products of frictional grinding processes. Dusts are different from soil in
that soil derives from crustal rock and typically has a lead concentration of 10 to 30 pg/g,
whereas dusts come from both natural and anthropogenic sources and vary from 1000 to 10,000
The route by which many people receive the largest portion of their daily lead intake is
via foods. Several studies have reported average dietary lead intakes in the range 100 to 500
ug/day for adults, with individual diets covering a much greater range (Nutrition Foundation,
1982). The sources of lead in plants and animals are air, soil, and untreated waters (Figure
1-13). Food crops and livestock contain lead in varying proportions from the atmosphere and
natural sources. From the farm to the dinner table, lead is added to food as it is harvested,
transported, processed, packaged, and prepared. The sources of this lead are dusts of atmos-
pheric and industrial origin, metals used in grinding, crushing, and sieving, solder used in
packaging, and water used in cooking. Pennington (1983) has identified 234 typical food cate-
gories for Americans grouped into eight age/sex groups. These basic diets are the foundation
for the Food and Drug Administration's revised Total Diet Study, often called the "Market
Basket Study", beginning in April, 1982. The diets used for this discussion include food,
beverages, and drinking water for the 2-year-old child, the adult female 25 to 30 years of
age, and the adult male 25 to 30 years of age.
Milk and foods are treated separately from water and beverages because solder and atmos-
pheric lead contribute significantly to each of these later dietary components (Figure 1-1).
Between the field and the food processor, lead is added to food crops. It is assumed
that this lead is all of direct atmospheric origin. Direct atmospheric lead can be deposited
directly on food materials by dry deposition, or it can be lead on dust which has collected on
other surfaces, then transferred to foods. For the purposes of this discussion, it is not
necessary to distinguish between these two forms, as both are a function of air concentration.
For some of the food items, data are available on lead concentrations just prior to fil-
ling of cans. In the case where the food product has not undergone extensive modification
(e.g. cooking or added ingredients), the added lead was most likely derived from the atmos-
phere or from the machinery used to handle the product.
From the "time a product is packaged in bottles, cans, or plastic containers until it is
opened in the kitchen, it may be assumed that no food item receives atmospheric lead. Most of
the lead which is added during this stage comes from the solder used to seal some types of
SUMPB/D 1-42 9/30/83
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PRELIMINARY DRAFT
TABLE 1-7. SUMMARY BY AGE AND SEX OF ESTIMATED AVERAGE LEVELS
OF LEAD INGESTED FROM MILK AND FOODS
Dietary consumption
(g/day)
2-yr-old
A. Dairy
B. Meat
C. Food crops
D. Canned food
Total
Child
381
113
260
58
812
Adult
Female
237
169
350
68
824
Adult
Male
344
288
505
82
1219
Lead consumption
ug/day
2-yr-old Adult
ug Pb/g*
0.013
0.036
0.022
0.24
Child
5.0
4.1
5.7
13.9
28.7
Female
3.1
6.1
7.7
16.3
33.2
Adult
Male
4.5
10.4
11.1
19.7
45.6
*Weighted average lead concentration in foods from Table 7-15 in Chapter 7 of this document.
cans. Estimates by the Food and Drug Administration, prepared in cooperation with the
National Food Processors Association, suggest that lead in solder contributes more than 66
percent of the lead in canned foods where a lead solder side seam was used. This lead is
thought to represent a contribution of 20 percent to the total lead consumption in foods.
The contribution of the canning process to overall lead levels in albacore tuna has been
reported by Settle and Patterson (1980). The study showed that lead concentrations in canned
tuna are elevated above levels in fresh tuna by a factor of 4000. Nearly all of the increase
results from leaching of the lead from the soldered seam of the can; tuna from an unsoldered
can is elevated by a factor of only 20 compared with tuna fresh from the sea.
It is assumed that no further lead is added to food packaged in plastic or paper con-
tainers, although there are no data to support or reject this assumption.
Studies that reflect contributions of lead added during kitchen preparation showed that
lead in acidic foods stored refrigerated in open cans can increase by a factor of 2 to 8 in
five days if the cans have a lead-soldered side seam not protected by an interior lacquer
coating (Capar, 1978). Comparable products in cans with the lacquer coating or in glass jars
showed little or no increase.
As a part of its program to reduce the total lead intake by children (0-5 years) to less
than 100 ug/day by 1988, the Food and Drug Administration estimated lead intakes for individ-
ual children in a large-scale food consumption survey (Beloian and McDowell, 1981). Between
1973 and 1978, intensive efforts were made by the food industry to remove sources lead from
infant food items. By 1980, there had been a 47 percent reduction in the age group 0-5 months
and a 7 percent reduction for 6-23 months. Most of this reduction was accomplished by the
removal of soldered cans used for infant formula.
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PRELIMINARY DRAFT
Because the Food and Drug Administration is actively pursuing programs to remove lead
from adult foods, it is probable that there will be a decrease in total dietary lead consump-
tion over the next decade independent of projected decreases in atmospheric lead concentra-
tion. With both sources of lead minimized, the lowest reasonable estimated dietary lead con-
sumption would be 10-15 ug/day for adults and children. This estimate assumes about 90 per-
cent of the direct atmospheric, solder lead and lead of undetermined origin would be removed
from the diet, leaving 8 ug from these sources and 3 (jg of natural and indirect atmospheric
lead.
There have been several studies in North America and Europe of the sources of lead in
drinking water. The baseline concentration of water across the whole United States is taken
to be 10 (jg/1, although 6-8 pg/1 are often cited in the literature for specific locations. A
recent study in Seattle, WA by Sharrett et al. (1982) showed that the age of the house and the
type of plumbing determined the lead concentration in tap water. Standing water from houses
newer than five years (copper pipes) averaged 31 ug/1, while houses less than 18 months old
averaged about 70 ug/1. Houses older than five years and houses with galvanized pipe averaged
less than 6 ug/1. The source of the water supply, the length of the pipe, and the use of
plastic pipes in the service line had little or no effect on the lead concentrations. It ap-
pears certain that the source of lead in new homes with copper pipes is the solder used to
join these pipes, and that this lead is eventually worn away with age.
Ingestion, rather than inhalation, of dust particles appears to be the greater problem in
the baseline environment, especially ingestion during meals and playtime activity by small
children. Although dusts are of complex origin, they may be conveniently placed into a few
categories relating to human exposure. Generally, the most convenient categories are house-
hold dusts, soil dust, street dusts, and occupational dusts. It is a characteristic of dust
particles that they accumulate on exposed surfaces and are trapped in the fibers of clothing
and carpets. Two other features of dusts are important. First, they must be described in
both concentration and amount; the concentration of lead in street dust may be the same in a
rural and urban environment, but the amount of dust may differ by a wide margin. Secondly,
each category represents some combination of sources. Household dusts contain some atmospher-
ic lead, some paint lead, and some soil lead; street dusts contain atmospheric, soil, and oc-
casionally paint lead. For the baseline human exposure, it is assumed that workers are not
exposed to occupational dusts, nor do they live in houses with interior leaded paints. Street
dust, soil dust, and some household dust are the primary sources for baseline potential human
exposure.
In considering the impact of street dust on the human environment, the obvious question
arises as to whether lead in street dust varies with traffic density. It appears that in non-
SUMPB/D 1-44 9/30/83
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PRELIMINARY DRAFT
urban environments, street dust ranges from 80 to 130 M9/9. whereas urban street dusts range
from 1,000 to 20,000 ng/g. For the purpose of estimating potential human exposure, an average
value of 90 pg/g in street dust is assumed for baseline exposure and 1500 pg/g in tne discuss-
ions of urban environments.
Household dust is also a normal component of the home environment. It accumulates on all
exposed surfaces, especially furniture, rugs, and windows!11s. In some households of workers
exposed occupationally to lead dusts, the worker may carry dust home in amounts too small for
efficient removal but containing lead concentrations much higher than normal baseline values.
Most of the dust values for nonurban household environments fall in the range of 50 to
500 ug/g. A value of 300 ug/g is assumed. The only natural lead in dust would be some frac-
tion of that derived from soil lead. A value of 10 ug/g seems reasonable, since some of the
soil lead is of atmospheric origin. Children ingest about 5 times as much dust as adults,
most of the excess being street dusts from sidewalks and playgrounds. Exposure to occupation-
al lead by children would be through clothing brought home by parents.
The values derived or assumed in the proceeding sections are summarized on Table 1-8.
These values represent only consumption, not absorption of lead by the human body.
1.7.6 Additional Exposures
There are many conditions, even in nonurban environments, where an individual may in-
crease his lead exposure by choice, habit, or unavoidable circumstance. These conditions are
discussed as separate exposures to be added as appropriate to the baseline of human exposure
described above. Most of these additive effects clearly derive from air or dust, few from
water or food. Ambient air lead concentrations are typically higher in an urban than a rural
environment. This factor alone can contribute significantly to the potential lead exposure of
Americans, through increases in inhaled air and consumed dust. Produce from urban gardens may
also increase the daily consumption of lead. Some environments may not be related only to
urban living, such as houses with interior lead paint or lead plumbing, residences near
smelters or refineries, or family gardens grown on high-lead soils. Occupational exposures
may also be in an urban or rural setting. These exposures, whether primarily in the occupa-
tional environment or secondarily in the home of the worker, would be in addition to other ex-
posures in an urban location or from the special cases of lead-based paint or plumbing.
Urban atmospheres. The fact that urban atmospheres have more airborne lead than nonurban
contributes not only to lead consumed by inhalation but also to increased amounts of lead in
dust. Typical urban atmospheres contain 0.5-1.0 ug Pb/m3. Other variable are the amount of
indoor filtered air breathed by urban residents, the amount of time spent indoors, and the
amount of time spent on freeways. Dusts vary from 500 to 3000 ug/g in urban environments.
SUMPB/D 1-45 9/30/83
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TABLE 1-8. SUMMARY OF BASELINE HUMAN EXPOSURES TO LEAD
Units are in rag/day
Soil
Source
Child-2 yr old
Inhaled Air
Food
Water & beverages
Dust
Total
Percent
Adult female
Inhaled air
Food
Water & beverages
Dust
Total
Percent
Adult male
Inhaled air
Food
Water & beverages
Dust
Total
Percent
Total
Lead
Consumed
0.5
28.7
11.5
21.0
61.4
100%
1.0
33.2
17.9
4.5
56.6
100%
1.0
45.7
25.1
4.5
76.3
100%
Natural
Lead
Consumed
0.001
0.9
0.01
0.6
1.5
2.4%
0.002
1.0
0.01
0.2
1.2
2.1%
0.002
1.4
0.1
0.2
1.7
2.2%
Indirect
Atmospheric
Lead*
-
0.9
2.1
-
3.0
4.9%
-
1.0
3.4
-
4.4
7.8%
-
1.4
4.7
-
6.1
8.0%
Direct
Atmospheric
Lead*
0.5
10.9
1.2
19.0
31.6
51.5%
1.0
12.6
2.0
2.9
18.5
32.7%
1.0
17.4
2.8
2.9
24.1
31.6%
Lead from
Solder or
Other Metals
-
10.3
7.8
-
18.1
29.5%
-
11.9
12.5
-
24.4
43.1%
-
16.4
17.5
-
33.9
44.4%
Lead of
Undetermi ned
Origin
-
17.6
-
1.4
19.0
22.6%
-
21.6
-
1.4
23.0
26.8%
-
31.5
-
1.4
32.9
27.1%
*Indirect atmospheric lead has been previously incorporated into soil, and will probably remain in the soil
for decades or longer. Direct atmospheric lead has been deposited on the surfaces of vegetation and living
areas or incorporated during food processing shortly before human consumption.
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PRELIMINARY DRAFT
Houses with interior lead paint. In 1974, the Consumer Product Safety Commission col-
lected household paint samples and analyzed them for lead content (National Academy of
Sciences, National Research Council, 1976).
Flaking paint can cause elevated lead concentrations in nearby soil. For example, Hardy
et al. (1971) measured soil lead levels of 2000 ug/g next to a barn in rural Massachusetts. A
steady decrease in lead level with increasing distance from the barn was shown, reaching 60
ug/g at fifty feet from the barn. Ter Haar and Arnow (1974) reported elevated soil lead
levels in Detroit near eighteen old wood frame houses painted with lead-based paint. The
average soil lead level within two feet of a house was just over 2000 ug/g; the average con-
centration at ten feet was slightly more than 400 ug/g. The same author reported smaller soil
lead elevations in the vicinity of eighteen brick veneer houses in Detroit. Soil lead levels
near painted barns located in rural areas were similar to urban soil lead concentrations near
painted houses, suggesting the importance of leaded paint at both urban and rural locations.
The baseline lead concentration for household dust of 300 ug/g was increased to 2000 H9/9 for
houses with interior lead based paints. The additional 1700 ug/g would add 85 ug Pb/day to
the potential exposure of a child. This increase would occur in an urban or nonurban environ-
ment and would be in addition to the urban residential increase if the lead-based painted
house were in an urban environment.
Family gardens. Several studies have shown potentially higher lead exposure through the
consumption of home-grown produce from family gardens grown on high lead soils or near sources
of atmospheric lead. In family gardens, lead may reach the edible portions of vegetables by
deposition of atmospheric lead directly onto aboveground plant parts or onto soil, or by tue
flaking of lead-containing paint chips from houses. Air concentrations and particle size dis-
tributions are the important determinants of deposition to soil or vegetation surfaces. Even
at relatively high air concentrations (1.5 ug/m3) and deposition velocity (0.5 cm/sec), it is
unlikely that surface deposition alone can account for more than 2-5 ug/g lead on the surface
of lettuce during a 21-day growing period. It appears that a significant fraction of the lead
in both leafy and root vegetables derives from the soil.
Houses with lead plumbing. The Glasgow Duplicate Diet Study (United Kingdom Directorate
on Environmental Pollution, 1982) reports that children approximately 13 weeks old living in
lead-plumbed houses consume 6-480 ug Pb/day. Water lead levels in the 131 homes studied
ranged from less than 50 to over 500 ug/1. Those children and mothers living in the homes
containing high water lead levels generally had greater total lead consumption and higher
blood lead levels, according to the study. Breast-fed infants were exposed to much less lead
than bottle-fed infants. The results of the study suggest that infants living in lead-plumbed
homes may have exposure to considerable amounts of lead. This conclusion was also demonstrat-
ed by Sherlock et al. (1982) in a duplicate diet study in Ayr, Scotland.
SUMPB/D 1-47 9/30/83
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PRELIMINARY DRAFT
Residences near smelters and refineries. Air concentrations within 2 km of lead smelters
and refineries average 5-15 |jg/m3. Between inhaled air and dust, a child in this circumstance
would be exposed to 1300 ug Pb/day above background levels. Exposures to adults would be much
less, since they consume only 20 percent of the dusts children consume.
Occupational exposures. The highest and most prolonged exposures to lead are found among
workers in the lead smelting, refining, and manufacturing industries (World Health Organiza-
tion, 1977). In all work areas, the major route of lead exposure is by inhalation and inges-
tion of lead-bearing dusts and fumes. Airborne dusts settle out of the air onto food, water,
the workers' clothing, and other objects, and may be subsequently transferred to the mouth.
Therefore, good housekeeping and good ventilation have a major impact on exposure. Even tiny
amounts (10 mg) of 100,000 ug/g dust can account for 1,000 ng/day exposure.
The greatest potential for high-level occupational exposure exists in the process of lead
smelting and refining. The most hazardous operations are those in which molten lead and lead
alloys are brought to high temperatures, resulting in the vaporization of lead, because con-
densed lead vapor or fume has, to a substantial degree, a small (respirable) particle size
range.
When metals that contain lead or are protected with a lead-containing coating are heated
in the process of welding or cutting, copious quantities of lead in the respirable size range
may be emitted. Under conditions of poor ventilation, electric arc welding of zinc silicate-
coated steel (containing 29 mg Pb/in2 of coating) produces breathing-zone concentrations of
lead reaching 15,000 ug/m3, far in excess of 450 ug/m3, the current occupational short-term
exposure limit in the United States. In a study of salvage workers using oxy-acetylene cut-
ting torches on lead-painted structural steel under conditions of good ventilation, breathing-
zone concentrations of lead averaged 1200 ug/m3 and ranged as high as 2400 ug/m3.
At all stages in battery manufacture except for final assembly and finishing, workers are
exposed to high air lead concentrations, particularly lead oxide dust. Excessive concentra-
tions, as great as 5400 ug/m3, have been quoted by the World Health Organization (1977). The
hazard in plate casting, which is a molten-metal operation, is from the spillage of molten
waste products, resulting in dusty floors.
Workers involved in the manufacture of both tetraethyl lead and tetramethyl lead, two
alkyl lead compounds, are exposed to both inorganic and alkyl lead. The major potential
hazard in the manufacture of tetraethyl lead and tetramethyl lead is from skin absorption, but
this is guarded against by the use of protective clothing.
In both the rubber products industry and the plastics industry there are potentially high
exposures to lead. The potential hazard of the use of lead stearate as a stabilizer in the
manufacture of polyvinyl chloride was noted in the 1971 United Kingdom Department of Employ-
ment, Chief Inspector of Factories (1972). The source of this problem is the dust that is
SUMPB/D 1-48 9/30/83
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PRELIMINARY DRAFT
generated when the lead stearate is milled and mixed with the polyvinyl chloride and the plas-
ticizer. An encapsulated stabilizer that greatly reduces the occupational hazard is reported
by Fischbein et al. (1982). Sakurai et al. (1974), in a study of bioindicators of lead expo-
sure, found ambient air concentrations averaging 58 ug/m3 in the lead-covering department of a
rubber hose manufacturing plant.
The manufacture of cans with leaded seams may expose workers to elevated environmental
lead levels. Bishop (1980) reports airborne lead concentrations of 25 to 800 ng/m3 in several
can manufacturing plants in the United Kingdom. Between 23 percent and 54 percent of the air-
borne lead was associated with respirable particles. Firing ranges may be characterized by
high airborne lead concentrations, hence instructors who spend considerable amounts of time in
such areas may be exposed to lead. Anderson et al. (1977) discuss plumbism in a 17-year-old
male employee of a New York City firing range, where airborne lead concentrations as great as
1000 ug/m3 were measured during sweeping operations. Removal of leaded paint from walls and
other surfaces in old houses may pose a health hazard. Feldman (1978) reports an airborne
lead concentration of 510 ug/m3, after 22 minutes of sanding an outdoor post coated with paint
containing 2.5 mg Pb/cm2. After only five minutes of sanding an indoor window sill containing
0.8-0.9 mg Pb/cm2, the air contained 550 ug/m3. Garage mechanics may be exposed to excessive
lead concentrations. Clausen and Rastogi (1977) report airborne lead levels of 0.2-35.5 ug/m3
in ten garages in Denmark; the greatest concentration was measured in a paint workshop. Used
motor oils were found to contain 1500-3500 ug Pb/g, while one brand of gear oil, unused, con-
tained 9280 ug Pb/g. The authors state that absorption through damaged skin could be an
important exposure pathway. Other occupations involving risk of lead exposure include stained
glass manufacturing and repair, arts and crafts, and soldering and splicing.
Secondary occupational exposure. The amount of lead contained in pieces of cloth 1 in2
cut from bottoms of trousers worn by lead workers ranged from 700 to 19,000 ug, with a median
of 2,640 ug. In all cases, the trousers were worn under coveralls. Dust samples from 25
households of smelter workers ranged from 120 to 26,000 ug/g, with a median of 2,400 ug/g.
Special habits or activities. The quantity of food consumed per body weight varies
greatly with age and somewhat with sex. A two-year-old child weighing 14 kg eats and drinks
1.5 kg food and water per day. This is 110 g/kg, or 3 times the consumption of an 80 kg adult
male, who eats 39 g/kg.
Children place their mouths on dust collecting surfaces and lick non-food items with
their tongues. This fingersucking and mouthing activity are natural forms of behavior for
young children which expose them to some of the highest concentrations of lead in their envi-
ronment. A single gram of dust may contain ten times more lead than the total diet of the
child.
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PRELIMINARY DRAFT
Lead is also present in tobacco. The World Health Association (1977) estimates a lead
content of 2.5-12.2 yg per cigarette; roughly two to six percent of this lead may be inhaled
by the smoker. The National Academy of Sciences (1980) has used these data to conclude that a
typical urban resident who smokes 30 cigarettes per day may inhale roughly equal amounts of
lead from smoking and from breathing urban air. The average adult consumption of table wine
in the U.S. is about 12 g. Even at 0.1 M9/9. which is ten times higher than drinking water,
wine does not appear to represent a significant potential exposure. At one liter/day,
however, lead consumption would be greater than the total baseline consumption. McDonald
(1981) points out that older wines with lead foil caps may represent a hazard, especially if
they have been damaged or corroded. Wai et al. (1979) found the lead content of wine rose
from 200 to 1200 |jg/liter when the wine was allowed to pass over the thin ring of residue left
by the corroded lead foil cap. Newer wines (1971 and later) use other means of sealing.
Pica is the compulsive, habitual consumption of non-food items. In the case of paint
chips and soil, this habit can present a significant lead exposure to the afflicted person.
There are very little data on the amounts of paint or soil eaten by children with varying de-
grees of pica. Exposure can only be expressed on a unit basis. Billick and Gray (1978) re-
port lead concentrations of 1000-5000 ug/cm2 in lead-based paint pigments. A single chip of
paint can represent greater exposure than any other source of lead. A gram of urban soil may
have 150-2000 pg lead.
Beyond the baseline level of human exposure, additional amounts of lead consumption are
largely a matter of individual choice or circumstance. Most of these additional exposures a-
rise directly or indirectly from atmospheric lead, and in one or more ways probably affect 90
percent of the American population. In some cases, the additive exposure can be fully quan-
tified and the amount of lead consumed can be added to the baseline consumption. These may be
continuous (urban residence), or seasonal (family gardening) exposures. Some factors can be
quantified on a unit basis because of wide ranges in exposure duration or concentration. For
example, factors affecting occupational exposure are air lead concentrations (10-4000 M9/m3),
use and efficiency of respirators, length of time of exposure, dust control techniques, and
worker training in occupational hygiene.
Ambient airborne lead concentrations showed no marked trend from 1965 to 1977. Over the
past five years, however, distinct decreases occurred. Mean urban air concentration has
dropped from 0.91 (jg/m 1977 to 0.32 pg/m in 1980. These decreases reflect the smaller lead
emissions from mobile sources in recent years. Airborne size distribution data indicate that
most of the airborne lead mass is found in submicron particles. Atmospheric lead is deposited
on vegetation and soil surfaces, entering the human food chain through contamination of grains
and leafy vegetables, of pasture lands, and of soil moisture taken up by all crops. Lead con-
tamination of drinking water supplies appears to originate mostly from within the distribution
system.
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PRELIMINARY DRAFT
Most people receive the largest portion of their lead intake through foods. Unprocessed
foods such as fresh fruits and vegetables receive lead by atmospheric deposition as well as
uptake from soil; crops grown near heavily traveled roads generally have greater lead levels
than those grown at greater distances from traffic. For many crops the edible internal por-
tions of the plant (e.g., kernels of corn and wheat) have considerably less lead than the
outer, more exposed parts such as stems, leaves, and husks. Atmospheric lead accounts for
about 30 percent of the total adult lead exposure, and 50 percent of the exposure for chil-
dren. Processed foods have greater lead concentrations than unprocessed foods, due to lead
inadvertently added during processing. Foods packaged in soldered cans have much greater lead
levels than foods packaged in other types of containers. About 45 percent of the baseline
adult exposure to lead results from the use of solder lead in packaging food and distributing
drinking water.
Significant amounts of lead in drinking water can result from contamination at the water
source and from the use of lead solder in the water distribution system. Atmospheric deposi-
tion has been shown to increase lead in rivers, reservoirs, and other sources of drinking
water; in some areas, however, lead pipes pose a more serious problem. Soft, acidic water in
homes with lead plumbing may have excessive lead concentrations. Besides direct consumption
of the water, exposure may occur when vegetables and other foods are cooked in water con-
taining lead.
All.of the categories of potential lead exposure discussed above may influence or be in-
fluenced by dust and soil. For example, lead in street dust is derived primarily from
vehicular emissions, while leaded house dust may originate from nearby stationary or mobile
sources. Food and water may include lead adsorbed from soil as well as deposited atmospheric
material. Flaking leadbased paint has been shown to increase soil lead levels. Natural con-
centrations of lead in soil average approximately 15 ug/g; this natural lead, in addition to
anthropogenic lead emissions, influences human exposure.
Americans living in rural areas away from sources of atmospheric lead consume 50 to 75 pg
Pb/day from all sources. Circumstances which can increase this exposure are: urban residence
(25 to 100 ug/day), family garden on high lead soil (800 to 2000 pg/day), houses with interior
lead-based paint (20 to 85 ug/day), and residence near a smelter (400 to 1300 ug/day). Occu-
pational settings, smoking and wine consumption also can increase consumption of lead accord-
ing to the degree of exposure.
A number of manmade materials are known to contain lead, the most important being paint
and plastics. Lead-based paints, although no longer used, are a major problem in older homes.
Small children who ingest paint flakes can receive excessive lead exposure. Incineration of
plastics may emit large amounts of lead into the atmosphere. Because of the increasing use of
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PRELIMINARY DRAFT
plastics, this source is likely to become more important. Other manmade materials containing
lead include colored dyes, cosmetic products, candle wicks, and products made of pewter and
silver.
The greatest occupational exposures are found in the lead smelting and refining indus-
tries. Excessive airborne lead concentrations and dust lead levels are occasionally found in
primary and secondary smelters; smaller exposures are associated with mining and processing of
the lead ores. Welding and cutting of metal surfaces coated with lead-based paint may also
result in excessive exposure. Other occupations with potentially high exposures to lead in-
clude the manufacture of lead storage batteries, printing equipment, alkyl lead, rubber pro-
ducts, plastics, and cans; individuals removing lead paint from walls and those who work in
indoor firing ranges may also be exposed to lead.
Environmental contamination by lead should be measured in terms of the total amount of
lead emitted to the biosphere. American industry contributes several hundred thousand tons of
lead to the environment each year: 35,000 tons from petroleum additives, 50,000 tons from am-
munition, 45,000 tons in glass and ceramic products, 16,000 tons in paint pigments, 8,000 tons
in food can solder, and untold thousands of tons of captured wastes during smelting, refining,
and coal combustion. These are uses of lead which are generally not recoverable, thus they
represent a permanent contamination of the human or natural environment. Although much of
this lead is confined to municipal and industrial waste dumps, a large amount is emitted to
the atmosphere, waterways, and soil, to become a part of the biosphere.
Potential human exposure can be expressed as the concentrations of lead in those environ-
mental components (air, dust, food, and water) that interface with man. It appears that, with
the exception of extraordinary cases of exposure, about 100 mg of lead are consumed daily by
each American. This amounts to only 8 tons, or less than 0.01 percent of the total environ-
mental contamination.
1.8 EFFECTS OF LEAD ON ECOSYSTEMS
The principle sources of lead entering an ecosystem are: the atmosphere (from automotive
emissions), paint chips, spent ammunition, the application of fertilizers and pesticides, and
the careless disposal of lead-acid batteries or other industrial products. Atmospheric lead
is deposited on the surfaces of vegetation as well as on ground and water surfaces. In ter-
restrial ecosystems, this lead is transferred to the upper layers of the soil surface, where
it may be retained for a period of several years. The movement of lead within ecosystems is
influenced by the chemical and physical properties of lead and by the biogeochemical pro-
perties of the ecosystem. Lead is non-degradable, but in the appropriate chemical' environ-
ment, may undergo transformations which affect its solubility (e.g., formation of lead sulfate
SUMPB/D 1-52 9/30/83
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PRELIMINARY DRAFT
in soils), its bioavailability (e.g., chelation with humic substances), or its toxicity (e.g.,
chemical methylation). Although the situation is extremely complex, it is reasonable to state
that most plants cannot survive in soil containing 10,000 pg lead/g dry weight if the pH is
below 4.5 and the organic content is below 5 percent.
There is wide variation in the mass transfer of lead from the atmosphere to terrestrial
ecosystems. Smith and Siccama (1981) report 270 g/ha-yr in the Hubbard Brook forest of New
Hampshire, Lindberg and Harriss (1981) found 50 g/ha-yr in the Walker Branch watershed of
Tennessee; and Elias et al. (1976) found 15 g/ha-yr in a remote subalpine ecosystem of
California. Jackson and Watson (1977) found 1,000,000 g/ha-yr near a smelter in southeastern
Missouri. Getz et al. (1979) estimated 240 g/ha-yr by wet precipitation alone in a rural eco-
system largely cultivated, and 770 g/ha-yr in an urban ecosystem.
One factor causing great variation is remoteness from source, which translates to lower
air concentrations, smaller particles, and greater dependence on wind as a mechanism of depo-
sition. Another factor is type of vegetation cover. Deciduous leaves may, by the nature of
their surface and orientation in the wind stream, be more suitable deposition surfaces than
conifer needles.
There are three known conditions under which lead may perturb ecosystem processes (see
Figured 1-12). At soil concentrations of 1000 ug/g or higher, delayed decomposition may
result from the elimination of a single population of decomposer microorganisms. Secondly, at
concentrations of 500-1000 ug/g, populations of plants, microorganisms, and invertebrates may
shift toward lead tolerant populations of the same or different species. Finally, the normal
biogeochemical process which purifies and repurifies calcium in grazing and decomposer food
chains may be circumvented by the addition of lead to vegetation and animal surfaces. This
third effect can be measured at all ambient atmospheric concentrations of lead.
Some additional effects may occur due to the uneven distribution of lead in ecosystems.
It is known that lead accumulates in soil, especially soil with high organic content.
Although no firm documentation exists, it is reasonable to assume from the known chemistry of
lead in soil that: (1) other metals may be displaced from binding sites on the organic
matter; (2) the chemical breakdown of inorganic soil fragments may be retarded by interference
of lead with the action of fulvic acid on iron bearing crystals; and (3) lead in soil may be
in equilibrium with moisture films surrounding soil particles and thus available for uptake by
plants.
Two principles govern ecosystem functions: (1) energy flows through an ecosystem; and
(2) nutrients cycle within an ecosystem. Energy usually enters the ecosystem in the form of
sunlight and leaves as heat of respiration. Unlike energy, nutrient and non-nutrient elements
are recycled by the ecosystem and transferred from reservoir to reservoir in a pattern usually
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GRAZERS
PRIMARY
PRODUCERS
INORGANIC
NUTRIENTS
Figure 1-12. This figure depicts cycling processes within the major components of a
terrestrial ecosystem, i.e. primary producers, grazers and decomposers. Nutrient and
non-nutrient elements are stored in reservoirs within these components. Processes
that take place within reservoirs regulate the flow of elements between reservoirs
along established pathways. The rate of flow is in part a function of the concentra-
tion in the preceding reservoir. Lead accumulates in decomposer reservoirs which
have a high binding capacity for this metal. It is likely that the rate of flow away
from these reservoirs has increased in past decades and will continue to increase for
some time until the decomposer reservoirs are in equilibrium with the entire
ecosystem. Inputs to and outputs from the ecosystem as a whole are not shown.
Source: Adapted from Swift et al. (1979).
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referred to as a biogeochemical cycle (Brewer, 1979, p. 139). The reservoirs correspond ap-
proximately to the food webs of energy flow. Although elements may enter (e.g., weathering of
soil) or leave the ecosystem (e.g., stream runoff), the greater fraction of the available mass
of the element is usually cycled within the ecosystem.
Ecosystems have boundaries. These boundaries may be as distinct as the border of a pond
or as arbitrary as an imaginary circle drawn on a map. Many trace metal studies are conducted
in watersheds where some of the boundaries are determined by topography. For atmospheric in-
puts to terrestrial ecosystems, the boundary is usually defined as the surface of vegetation,
exposed rock or soil. Non-nutrient elements differ little from nutrient elements in their
biogeochemical cycles. Quite often, the cycling patterns are similar to those of a major
nutrient. In the case of lead, the reservoirs and pathways are very similar to those of
calcium.
Naturally occurring lead from the earth's crust is commonly found in soils and the atmos-
phere. Lead may enter an ecosystem by weathering of parent rock or by deposition of atmos-
pheric particles. This lead becomes a part of the nutrient medium of plants and the diet of
animals. All ecosystems receive lead from the atmosphere.
In prehistoric times, the contribution of lead from weathering of soil was probably about
4g Pb/ha-yr and from atmospheric deposition about 0.02 g Pb/ha-yr. Weathering rates are pre-
sumed to have remained the same, but atmospheric inputs are believed to have increased to
180 g/ha-yr in natural and some cultivated ecosystems, and 3000 g/ha-yr in urban ecosystems
and along roadways. In every terrestrial ecosystem of the Northern Hemisphere, atmospheric
lead deposition now exceeds weathering by a factor of at least 10, sometimes by as much as
1000.
Many of the effects of lead on plants, microorganisms, and ecosystems arise from the fact
that lead from atmospheric and weathering inputs is retained by soil. Geochemical studies
show that less than 3 percent of the inputs to a watershed leave by stream runoff. Lead in
natural soils now accumulates on the surface at an annual rate of 5-10 percent of the natural
lead. One effect of cultivation is that atmospheric lead is mixed to a greater depth than the
0-3 cm of natural soils.
Most of the effects on grazing vertebrates stem from the deposition of atmospheric par-
ticles on vegetation surfaces. Atmospheric deposition may occur by either of two mechanisms.
Wet deposition (precipitation scavenging through rainout or washout) generally transfers lead
directly to the soil. Dry deposition transfers particles to all exposed surfaces. Large par-
ticles (>4 urn) are transferred by gravitational mechanisms, small particles (<0.5 urn) are also
deposited by wind-related mechanisms.
If the air concentration is known, ecosystem inputs from the atmosphere can be predicted
over time and under normal conditions. These inputs and those from the weathering of soil
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determine the concentration of lead in the nutrient media of plants, animals, and micro-
organisms. It follows that the concentration of lead in the nutrient medium determines the
concentration of lead in the organism and this in turn determines the effects of lead on the
organism. The fundamental nutrient medium of a terrestrial ecosystem is the soil moisture
film which surrounds organic and inorganic soil particles. This film of water is in equi-
librium with other soil components and provides dissolved inorganic nutrients to plants.
Studies have shown the lead content of leafy vegetation to be 90 percent anthropogenic,
even in remote areas (Crump and Barlow, 1980; Elias et al., 1976, 1978). The natural lead
content of nuts and fruits may be somewhat higher than leafy vegetation, based on internal
lead concentrations of modern samples (Elias et al. 1982).
Because lead in soil is the source of most effects on plants, microorganisms, and eco-
systems, it is important to understand the processes that control the accumulation of lead in
soil. Major components of soil are: (1) fragments of inorganic parent rock material-
(2) secondary inorganic minerals; (3) organic constituents, primarily humic substances, which
are residues of decomposition or products of decomposer organisms; (4) Fe-Mn oxide films
which coat the surfaces of all soil particles and have a high binding capacity for metals;
(5) soil microorganisms, most commonly bacteria and fungi, although protozoa and soil algae may
also be found; and (6) soil moisture, the thin film of water surrounding soil particles which
is the nutrient medium of plants.
The concentration of lead ranges from 5 to 30 ug/g in the top 5 cm of most soils not
adjacent to sources of industrial lead, although 5 percent of the soils contain as much .as
800 ug/g. Aside from surface deposition of atmospheric particles, plants in North America
average about 0.5-1 ug/g dw (Peterson, 1978) and animals roughly 2 ug/g (Forbes and Sanderson,
1978). Thus, soils contain the greater part of total ecosystem lead. In soils, lead in
parent rock fragments is tightly bound within the crystalline structures of the inorganic soil
minerals. It is released to the ecosystem only by surface contact with soil moisture films.
Hutchinson (1980) has reviewed the effects of acid precipitation on the ability of soils
to retain cations. Excess calcium and other metals are leached from the A horizon of soils by
rain with a pH more acidic than 4.5. Most soils in the eastern United States are normally
acidic (pH 3.5-5.2) and the leaching process is a part of the complex equilibrium maintained
in the soil system. By increasing the leaching rate, acid rain can reduce the availability of
nutrient metals to organisms dependent on the top layer of soil. It appears that acidifica-
tion of soil may increase the rate of removal of lead from the soil, but not before several
major nutrients are removed first. The effect of acid rain on the retention of lead by soil
moisture is not known.
Atmospheric lead may enter aquatic ecosystems by wet or dry deposition or by the
erosional transport of soil particles. In waters not polluted by industrial, agricultural, or
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municipal effluents, the lead concentration is usually less than 1 ug/1. Of this amount,
approximately 0.02 ug/1 is natural lead and the rest is anthropogenic lead, probably of atmos-
pheric origin (Patterson, 1980). Surface waters mixed with urban effluents may frequently
reach lead concentrations of 50 ug/1, and occasionally higher. In still water, lead is
removed from the water column by the settling of lead-containing particulate matter, by the
formation of insoluble complexes, or by the adsorption of lead onto suspended organic
particles. The rate of sedimentation is determined by temperature, pH, oxidation-reduction
potential, ionic competition, the chemical form of lead in water, and certain biological acti-
vities (Jenne and Luoma, 1977). McNurney et al. (1977) found 14 ug Pb/g in stream sediments
draining cultivated areas and 400 ug/g in sediments associated with urban ecosystems.
1.8.1 Effects on Plants
Some physiological and biochemical effects of lead on vascular plants have been detected
under laboratory conditions at concentrations higher than normally found in the environment.
The commonly reported effects are the inhibition of photosynthesis, respiration or cell elon-
gation, all of which reduce the growth of the plant (Koeppe, 1981). Lead may also induce pre-
mature senescence, which may affect the long-term survival of the plant or the ecological suc-
cess of the plant population. Most of the lead in or on a plant occurs on the surfaces of
leaves and the trunk or stem. The surface concentration of lead in trees, shrubs, and grasses
exceeds the internal concentration by a factor of at least five (Elias et al, 1978). There is
little or no evidence of lead uptake through leaves or bark. Foliar uptake, if it does occur,
cannot account for more than 1 percent of the uptake by roots, and passage of lead through
bark tissue has not been detected (Arvik and Zimdahl, 1974; reviewed by Koeppe, 1981; Zimdahl,
1976). The major effect of surface lead at ambient concentrations seems to be on subsequent
components of the grazing food chain and on the decomposer food chain following litterfall
(Elias et al., 1982).
Uptake by roots is the only major pathway for lead into plants. The amount of lead that
enters plants by this route is determined by the availability of lead in soil, with apparent
variations according to plant species. Soil cation exchange capacity, a major factor, is de-
termined by the relative size of the clay and organic fractions, soil pH, and the amount of
Fe-Mn oxide films present (Nriagu, 1978). Of these, organic humus and high soil pH are the
dominant factors in immobilizing lead. Under natural conditions, most of the total lead in
soil would be tightly bound within the crystalline structure of inorganic soil fragments, un-
available to soil moisture. Available lead, bound on clays, organic colloids, and Fe-Mn
films, would be controlled by the slow release of bound lead from inorganic rock sources. Be-
cause lead is strongly immobilized by humic substances, only a small fraction (perhaps 0.01 -
percent in soils with 20 percent organic matter, pH 5.5) is released to soil moisture.
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Two defensive mechanims appear to exist in the roots of plants for removing lead from the
stream of nutrients flowing to the above-ground portions of plants. Lead may be deposited
with cell wall material exterior to the individual root cells, or may be sequestered in organ-
elles within the root cells. Any lead not captured by these mechanisms would likely move with
nutrient metals cell-to-cell through the symplast and into the vascular system. Uptake of
lead by plants may be enhanced by symbiotic associations with mycorrhizal fungi. The three
primary factors that control the uptake of nutrients by plants are the surface area of the
roots, the ability of the root to absorb particular ions, and the transfer of ions through the
soil. The symbiotic relationship between mycorrhizal fungi and the roots of higher plants can
increase the uptake of nutrients by enhancing all three of these factors.
The translocation of lead to aboveground portions of the plant is not clearly understood.
Lead may follow the same pathway and be subject to the same controls as a nutrient metal such
as calcium. There may be several mechanisms that prevent the translocation of lead to other
plant parts. The primary mechanisms may be storage in cell organelles or adsorption on cell
walls. Some lead passes into the vascular tissue, along with water and dissolved nutrients
and is carried to physiologically active tissue of the plant. Evidence that lead in contami-
nated soils can enter the vascular system of plants and be transported to aboveground parts
may be found in the analysis of tree rings. These chronological records confirm that lead can
be translocated in proportion to the concentrations of lead in soil.
Because most of the physiologically active tissue of plants is involved in growth, main-
tenance, and photosynthesis, it is expected that lead might interfere with one or more of
these processes. Indeed, such interferences have been observed in laboratory experiments at
lead concentrations greater than those normally found in the field, except near smelters or
mines (Koeppe, 1981). Inhibition of photosynthesis by lead may be by direct interference with
the light reaction or the indirect interference with carbohydrate synthesis. Miles et al.
(1972) demonstrated substantial inhibition of photosystem II near the site of water splitting,
a biochemical process believed to require manganese. Devi Prasad and Devi Prasad (1982) found
10 percent inhibition of pigment production in three species of green algae at 1 ug/g, in-
creasing to 50 percent inhibition at 3 ug/g. Bazzaz et al. (1974, 1975) observed reduced net
photosynthesis which may have been caused indirectly by inhibition of carbohydrate synthesis.
The stunting of plant growth may be by the inhibition of the growth hormone IAA (indole-
3-ylacetic acid). Lane et al. (1978) found a 25 percent reduction in elongation at 10 pg/g
lead as lead nitrate in the nutrient medium of wheat coleoptiles. Lead may also interfere
with plant growth by reducing respiration or inhibiting cell division. Miller and Koeppe
(1971) and Miller et al. (1975) showed succinate oxidation inhibition in isolated mitochondria
as well as stimulation of exogenous NADH oxidation with related mitochondrial swelling.
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Hassett et al. (1976), Koeppe (1977), and Malone et al. (1978) described significant inhibi-
tion of lateral root initiation in corn. The interaction of lead with calcium has been shown
by several authors, most recently by Garland and Wilkins (1981), who demonstrated that barley
seedlings (Hordeum vulgare), which were growth inhibited at 2 jjg Pb/g sol. with no added
calcium, grew at about half the control rate with 17 ug Ca/g sol. This relation persisted up
to 25 (jg Pb/g sol. and 500 |jg Ca/g sol.
These studies of the physiological effects of lead on plants all show some effect at con-
centrations from 2 to 10 ug/g in the nutrient medium of hydroponically-grown agricultural
plants. It is certain that no effects would have been observed at these concentrations had
the lead solutions been added to normal soil, where the lead would have been bound by humic
substances. There is no firm relationship between soil lead and soil moisture lead, because
each soil type has a unique capacity to retain lead and to release that lead to the soil
moisture film surrounding the soil particle. Once in soil moisture, lead seems to pass freely
to the plant root according to the capacity of the plant root to absorb water and dissolved
substances.
It seems reasonable that there may be a direct correlation between lead in hydroponic
media and lead in soil moisture. Hydroponic media typically have an excess of essential
nutrients, including calcium and phosphorus, so that movement of lead from hydroponic media to
plant root would be equal to or slower than movement from soil moisture to plant root.
Even .under the best of conditions where soil has the highest capacity to retain lead,
most plants would experience reduced growth rate (inhibition of photosynthesis, respiration,
or cell elongation) in soils containing 10,000 pg Pb/g or greater. Concentrations approaching
this value typically occur around smelters and near major highways. These conclusions pertain
to soil with the ideal composition and pH to retain the maximum amount of lead. Acid soils or
soils lacking organic matter would inhibit plants at much lower lead concentrations.
The rate at which atmospheric lead accumulates in soil varies from 1.1 mg/m2-yr average
global deposition to 3000 mg/m2'yr near a smelter. Assuming an average density of 1.5 g/cm3,
undisturbed soil to a depth of 2 cm (20,000 cm3/m2) would incur an increase in lead concen-
tration at a rate of 0.04 to 100 ug/g soil-yr. This means remote or rural area soils may
never reach the 10,000 M9/9 threshold but that undisturbed soils closer to major sources may
be within range in the next 50 years.
Some plant species have developed populations tolerant to high lead soils. Using popu-
lations taken from mine waste and uncontaminated control areas, some authors have quantified
the degree of tolerance of Agrostis tenuis (Karataglis, 1982) and Festuca rubra (Wong, 1982)
under controlled laboratory conditions. Root elongation was used as the index of tolerance.
At 36 (jg Pb/g nutrient solution, all populations of A. tenuis were completely inhibited. At
12 M9 pb/9. tne control populations from low lead soils were completely inhibited, but the
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populations from mine soils achieved 30 percent of their normal growth (growth at no lead in
nutrient solution). At 6 H9/9. the control populations achieved 10 percent of their normal
growth, tolerant populations achieved 42 percent. There were no measurements below 6 ug/g.
These studies support the conclusion that inhibition of plant growth begins at a lead concen-
tration of less than 1 |jg/g soil moisture and becomes completely inhibitory at a level between
3 and 10 ug/g. Plant populations that are genetically adapted to high lead soils may achieve
50 percent of their normal root growth at lead concentrations above 3 H9/9-
When soil conditions allow lead concentrations in soil moisture to exceed 2-10 pg/g, most
plants experience reduced growth due to the inhibition of one or more physiological processes.
Excess calcium or phosphorus may reverse the effect. Plants that absorb nutrients from deeper
soil layers may receive less lead. Acid rain is not likely to release more lead until after
major nutrients have been depleted from the soil. A few species of plants have the genetic
capability to adapt to high lead soils.
Tyler (1972) explained three ways in which lead might interfere with the normal decompo-
sition processes in a terrestrial ecosystem. Lead may be toxic to specific groups of decom-
posers, it may deactivate enzymes excreted by decomposers to break down organic matter, or it
may bind with the organic matter to render it resistant to the action of decomposers. Because
lead in litter may selectively inhibit decomposition by soil bacteria at 2000-5000 ug/g,
forest floor nutrient cycling processes may be seriously disturbed near lead smelters. This
is especially important because approximately 70 percent of plant biomass enters the de-
composer food chain. If decomposition of the, biomass is inhibited, then much of the energy
and nutrients remain unavailable to subsequent components of the food chain. There is also
the possibility that the ability of soil to retain lead would be reduced, as humic substances
are byproducts of bacterial decomposition. Because they are interdependent, the absence of
one decomposer group in the decomposition food chain seriously affects the success of sub-
sequent groups, as well as the rate at which plant tissue decomposes. Each group may be
affected in a different way and at different lead concentrations. Lead concentrations toxic
to decomposer microbes may be as low as 1 to 5 ug/g or as high as 5000 ug/g. Under conditions
of mild contamination, the loss of one sensitive bacterial population may result in its
replacement by a more lead-tolerant strain. Delayed decomposition has been reported near
smelters, mine waste dumps, and roadsides. This delay is generally in the breakdown of litter
from the first stage (0,) to the second (02), with intact plant leaves and twigs accumulating
at the soil surface. The substrate concentrations at which lead inhibits decomposition appear
to be very low.
The conversion of ammonia to nitrate in soil is a two-step process mediated by two genera
of bacteria, Nitrosomonas and Nitrobacter. Nitrate is required by all plants, although some
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maintain a symbiotic relationship with nitrogen-fixing bacteria as an alternate source of ni-
trogen. Those which do not would be affected by a loss of free-living nitrifying bacteria,
and it is known that many trace metals inhibit this nitrifying process. Lead is the least of
these, inhibiting nitrification 14 percent at concentrations of 1000 ug/g soil. Even a 14
percent inhibition of nitrification can reduce the potential success of a plant population, as
nitrate is usually the limiting nutrient in terrestrial ecosystems.
It appears that microorganisms are more sensitive than plants to soil lead pollution and
that changes in the composition of bacterial populations may be an early indication of lead
effects. Delayed decomposition may occur at 750 ug Pb/g soil and nitrification inhibition at
1000 ug/g.
1.8.2 Effects on Animals
Forbes and Sanderson (1978) have reviewed reports of lead toxicity in domestic and wild
animals. Lethal toxicity can usually be traced to consumption of lead battery casings, lead-
based paints, oil wastes, putty, linoleum, pesticides, lead shot, or forage near smelters.
Awareness of the routes of uptake is important in interpreting the exposure and accumulation
in vertebrates. Inhalation rarely accounts for more than 10 to 15 percent of the daily intake
of lead (National Academy of Sciences, 1980). Food is the largest contributor of lead to ani-
mals. The type of food an herbivore eats determines the rate of lead ingestion. More than 90
percent of the total lead in leaves and bark may be surface deposition, but relatively little
surface deposition may be found on some fruits, berries, and seeds which have short exposure
times. Roots intrinsically have no surface deposition. Similarly, ingestion of lead by a
carnivore depends mostly on deposition on herbivore fur and somewhat less on lead in herbivore
tissue.
The type of food eaten is a major determinant of lead body burdens in small mammals.
Goldsmith and Scanlon (1977) and Scanlon (1979) measured higher lead concentrations in insec-
tivorous species than in herbivorous, confirming the earlier work of Quarles et al. (1974)
which showed body burdens of granivores
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Hematological and neurological responses are the most commonly reported effects of
extended lead exposures in aquatic vertebrates. Hematological effects include the disabling
and destruction of mature red blood cells and the inhibition of the enzyme ALA-D required for
hemoglobin synthesis. At low exposures, fish compensate by forming additional red blood
cells. These red blood cells often do not reach maturity. At higher exposures, the fish
become anemic. Symptoms of neurological responses are difficult to detect at low exposure
but higher exposure can induce neuromuscular distortion, anorexia, and muscle tremors. Spinal
curvature eventually occurs with time or increased concentration.
Insects have lead concentrations that correspond to those found in their habitat and
diet. Herbivorous invertebrates have lower concentrations than do predatory types. Among the
herbivorous groups, sucking insects have lower lead concentrations than chewing insects
especially in regions near roadsides, where more lead is found on vegetation surfaces.
Williamson and Evans (1972) found that gradients away from roadsides are not the same as with
vertebrates, in that invertebrate lead decreases more slowly than vertebrate lead relative to
decreases in soil lead. In Cepaea hortensis. a terrestrial snail, Williamson (1979) found
most of the lead in the digestive gland and gonadal tissue. A continuation of the study
(Williamson, 1980) showed that body weight, age, and daylength influenced the lead concentra-
tions in soft tissues. Beeby and Eaves (1983) addressed the question of whether uptake of
lead in the garden snail, Helix aspersa, is related to the nutrient requirement for calcium
during shell formation and reproductive activity. They found both metals were strongly cor-
related with changes in dry weight and little evidence for correlation of lead with calcium
independent of weight gain or lo^s.
Gish and Christensen (1973) found lead in whole earthworms to be correlated with soil
lead, with little rejection of lead by earthworms. Consequently, animals feeding on earth-
worms from high lead soils might receive toxic amounts of lead in their diets, although there
was no evidence of toxic effects on the earthworms. Ash and Lee (1980) cleared the digestive
tracts of earthworms and still found direct correlation of lead in earthworms with soil lead-
in this case, soil lead was inferred from fecal analyses. Ireland and Richards (1977) also
found some localization of lead in subcellular organelles of chloragogue and intestinal
tissue. In view of the fact that chloragocytes are believed to be involved with waste storage
and glycogen synthesis, the authors concluded that this tissue is used to sequester lead in
the manner of vertebrate livers.
Borgmann et al. (1978) found increased mortality in a freshwater snail, Lymnaea p_alutris
associated with stream water with a lead content as low as 19 ug/1. Full life cycles were
studied to estimate population productivity. Although individual growth rates were not
affected, increased mortality, especially at the egg hatching stage, effectively reduced total
biomass production at the population level. Production was 50 percent at 36 pg/1 and 0 per-
cent at 48 H9 Pb/1-
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While it is impossible to establish a safe limit of daily lead consumption, it is reason-
able to generalize that a regular diet of 2 to 8 mg Pb/kg-day body weight over an extended
period of time (Botts, 1977) will cause death in most animals. Animals of the grazing food
chain are affected most directly by the accumulation of aerosol particles on vegetation sur-
faces, and somewhat indirectly by the uptake of lead through plant roots. Many of f.hese
animals consume more than 1 mg Pb/kg«day in habitats near smelters and roadsides, but no toxic
effects have been documented. Animals of the decomposer food chain are affected indirectly by
lead in soil which can eliminate populations of microorganisms preceeding animals in the food
chain or occupying the digestive tract of animals and aiding in the breakdown of organic mat-
ter. Invertebrates may also accumultate lead at levels toxic to their predators.
Aquatic animals are affected by lead at water concentrations lower than previously con-
sidered safe (50 ug Pb/1) for wildlife. These concentrations occur commonly, but the contri-
bution of atmospheric lead to specific sites of high aquatic lead is not clear.
1.8.3 Effects on Microogam'sms
Recent studies have shown three areas of concern where the effects of lead on ecosystems
may be extremely sensitive. First, decomposition is delayed by lead, as some decomposer
microorganisms and invertebrates are inhibited by soil lead. Secondly, the natural processes
of calcium biopurification are circumvented by the accumulation of lead on the surfaces of
vegetation and in the soil reservoir. Thirdly, some ecosystems experience subtle shifts
toward lead tolerant plant populations. These problems all arise because lead in ecosystems
is deposited on vegetation surfaces, accumulates in the soil reservoir, and is not remover
with the surface and ground water passing out of the ecosystem.
Terrestrial ecosystems, especially forests, accumulate a tremendous amount of cellulose
as woody tissue of trees. Few animals can digest cellulose and most of these require
symbiotic associations with specialized bacteria. It is no surprise then, that most of this
cellulose must eventually pass through the decomposer food chain. Because 80 percent or more
of net primary production passes through the decomposing food chain, the energy of this litter
is vital to the rest of the plant community and the inorganic nutrients are vital to plants.
The amount of lead that causes litter to be resistant to decomposition is not known.
Doelman and Haanstra (1979a) demonstrated the effects of soil lead content on delayed decom-
position: sandy soils lacking organic complexing compounds showed a 30 percent inhibition of
decomposition at 750 ug/g, including the complete loss of major bacterial species, whereas the
effect was reduced in clay soils and non-existent in peat soils. Organic matter maintains the
cation exchange capacity of soils. A reduction in decomposition rate was observed by Doelman
and Haanstra (1979a) even at the lowest experimental concentration of lead, leading to the
conclusion that some effect might have occurred at even lower concentrations.
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1.8.4 Effects on Ecosystems
When decomposition is delayed, nutrients may be limiting to plants. In tropical regions
or areas with sandy soils, rapid turnover of nutrients is essential for the success of the
forest community. Even in a mixed deciduous forest, a significant portion of the nutrients
especially nitrogen and sulfur, may be found in the litter reservoir (Likens et al. 1977)
Annual litter inputs of calcium and nitrogen to the soil account for about 60 percent of root
uptake. With delayed decomposition, plants must rely on precipitation and soil weathering for
the bulk of their nutrients. Furthermore, the organic content of soil may decrease, reducing
the cation exchange capacity of soil.
Biopurification is a process that regulates the relative concentrations of nutrient to
non-nutrient elements in biological components of a food chain. In the absence of absolute
knowledge of natural lead concentrations, biopurification can be a convenient method for esti-
mating the degree of contamination. It is now believed that members of grazing and decomposer
food chains are contaminated by factors of 30-500, i.e., that 97-99.9 percent of the lead in
organisms is of anthropogenic origin. Burnett and Patterson (1980) have shown a similar pat-
tern for a marine food chain.
It has been observed that plant communities near smelter sites are composed mostly of
lead tolerant plant populations. In some cases, these populations appear to have adapted to
high lead soils, since populations of the same species from low lead soils often do not thrive
on high lead soils. In some situations, it is clear that soil lead concentration has become
the dominant factor in determining the success of plant populations and the stability of the
ecological community.
Inputs of natural lead to ecosystems, approximately 90 percent from rock weathering and
10 percent from atmospheric sources, account for slightly more than the hydrologic lead out-
puts in most watersheds. The difference is small and accumulation in the ecosystem is sig-
nificant only over a period of several thousand years. In modern ecosystems, with atmospheric
inputs exceeding weathering by factors of 10-1000, greater accumulation occurs in soils and
this reservoir must be treated as lacking a steady state condition. Odum and Drifmeyer (1978)
describe the role of detrital particles in retaining a wide variety of pollutant substances,
and this role may be extended to include non-nutrient substances.
It appears that plant communities have a built-in mechanism for purifying their own
nutrient medium. As a plant community matures through successional stages, the soil profile
develops a stratified arrangement which retains a layer of organic material near the surface.
This organic layer becomes a natural site for the accumulation of lead and other non-nutrient
metals which might otherwise interfere with the uptake and utilization of nutrient metals.
But the rate of accumulation of lead in this reservoir may eventually exceed the capacity of
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the reservoir. Johnson et al. (1982a) have established a baseline of 80 stations in forests
of the northeast United States. In the litter component of the forest floor, they measured an
average lead concentration of 150 ug/g. Near a smelter, they measured 700 ug/g and near a
highway, 440 ug/g. They presented some evidence from buried litter that predevelopment con-
centrations were 24 ug/g.
Lead in the detrital reservoir is determined by the continued input of atmospheric lead
from the litter layer, the passage of detritus through the decomposer food chain, and the rate
of leaching into soil moisture. There is strong evidence that soil has a finite capacity to
retain lead. Harrison et al. (1981) observed that most of the lead in roadside soils above
200 H9/9 1S found on Fe-Mn oxide films or as soluble lead carbonate. Lead is removed from the
detrital reservoir by the digestion of organic particles in the detrital food chain and by the
release of lead to soil moisture. Both mechanisms result in a redistribution of lead among
all of the reservoirs of the ecosystem at a very slow rate.
Fulvic acid plays an important role in the development of the soil profile. This organic
acid has the ability to remove iron from the lattice structures of inorganic minerals, result-
ing in the decomposition of these minerals as a part of the weathering process. This break-
down releases nutrients for uptake by pla.nt roots. If all binding sites on fulvic acid are
occupied by lead, the role of fulvic acid in providing nutrients to plants will be circum-
vented. While it is reasonably certain that such a process is possible, there is no informa-
tion about the soil lead concentrations that would cause such an effect.
Ecosystem inputs of lead by the atmospheric route have established new pathways and
widened old ones. Insignificant amounts of lead are removed by surface runoff or ground water
seepage. It is likely that the ultimate fate of atmospheric lead will be a gradual elevation
in lead concentration of all reservoirs in the system, with most of the lead accumulating in
the detrital reservoir.
Because there is no protection from industrial lead once it enters the atmosphere, it is
important to fully understand the effects of industrial lead emissions. Of the 450,000 tons
emitted annually on a global basis, 115,000 tons of lead fall on terrestrial ecosystems.
Evenly distributed, this would amount to 0.1 g/ha-yr, which is much lower than the range of 15
to 1,000,000 g/ha-yr reported in ecosystem studies in the United States. Lead has permeated
these ecosystems and accumulated in the soil reservoir where it will remain for decades. With-
in 20 meters of every major highway, up to 10,000 ug Pb have been added to each gram of sur-
face soil since 1930 (Getz et al., 1979). Near smelters, mines, and in urban areas, as much
as 130,000 ug/g have been observed in the upper 2.5 cm of soil (Jennett et al., 1977). At
increasing distances up to 5 kilometers away from sources, the gradient of lead added since
1930 drops to less than 10 ug/g (Page and Ganje, 1970), and 1 to 5 ug/g have been added in
regions more distant than 5 kilometers (Nriagu, 1978). In undisturbed ecosystems, atmospheric
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lead is retained by soil organic matter in the upper layer of soil surface. In cultivated
soils, this lead is mixed with soil to a depth of 25 cm.
Because of the special nature of the soil reservoir, it must not be regarded as an infi-
nite sink for lead. On the contrary, atmospheric lead which is already bound to soil will
continue to pass into the grazing and detrital food chains until equilibrium is reached,
whereupon the lead in all reservoirs will be elevated proportionately higher than natural
background levels. This conclusion applies also to cultivated soils, where lead bound within
the upper 25 cm is still within the root zone.
Few plants can survive at soil concentrations in excess of 10,000 ug/g, even under opti-
mum conditions. Some key populations of soil microorganisms and invertebrates die off at 1000
ug/g. Herbivores, in addition to a normal diet from plant tissues, receive lead from the sur-
faces of vegetation in amounts that may be 10 times greater than from internal plant tissue.
A diet of 2 to 8 mg/daykg body weight seems to initiate physiological dysfunction in many
vertebrates.
1.8.5 Summary
Some of the known effects, which are documented in detail in the appropriate sections,
are summarized here:
(1) Plants. The basic effect of lead on plants is to stunt growth. This may be through a
.reduction of photosynthetic rate, inhibition of respiration, cell elongation, or root develop-
ment, or premature senescence. Some genetic effects have been reported. All of these effects
have been observed in isolated cells or in hydroponically-grown plants in solutions comparable
to 1-2 mg lead/g soil moisture. These concentrations are well above those normally found in
any ecosystem except near smelters or roadsides. Terrestrial plants take up lead from the
soil moisture and most of this lead is retained by the roots. There is no evidence for foliar
uptake of lead and little evidence that lead can be translocated freely to the upper portions
of the plant. Soil applications of calcium and phosphorus may reduce the uptake of lead by
roots.
(2) Animals. Lead affects the central nervous system of animals and their ability to synthe-
size red blood cells. Blood concentrations above 0.4 mg/g (40 ug/dl) can cause observable
clinical symptoms in domestic animals. Calcium and phosphorus can reduce the intestinal
absorption of lead.
(3) Microorganisms. There is evidence that lead at environmental concentrations occasionally
found near roadsides and smelters (10,000-40,000 mg/g dw) can eliminate populations of bac-
teria and fungi on leaf surfaces and in soil. Many of those microorganisms play key roles in
the decomposition food chain. It is likely that the microbial populations are replaced by
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others of the same or different species, perhaps less efficient at decomposing organic matter.
There is also evidence that microorganisms can mobilize lead by making it more pheric parti-
cles. This lead becomes a part of the nutrient medium of plants and the diet of animals. All
ecosystems receive lead from the atmosphere.
Perhaps the most subtle effect of lead is on ecosystems. The normal flow of energy
through the decomposer food chain may be interrupted, the composition of communities may shift
toward more lead-tolerant populations, and new biogeochemical pathways may be opened, as lead
flows into and throughout the ecosystem. The ability of an ecosystem to compensate for atmos-
pheric lead inputs, especially in the presence of other pollutants such as acid precipita-
tion, depends not so much on factors of ecosystem recovery, but on undiscovered factors of ec-
osystem stability. Recovery implies that inputs of the perturbing pollutant have ceased and
that the pollutant is being removed from the ecosystem. In case of lead, the pollutant is not
being eliminated from the system nor are the inputs ceasing. Terrestrial ecosystems will
never return to their original, pristine levels of lead concentrations.
1.9 QUANTITATIVE EVALUATION OF LEAD AND BIOCHEMICAL INDICES OF LEAD EXPOSURE IN PHYSIOLOGICAL
MEDIA
The sine qua non of a complete understanding of a toxic agent's effects on an organism,
e.g., dose-effect relationships, is quantitative measurement of either that agent in some bio-
logical medium or a physiological parameter associated with exposure to the agent. Quantita-
tive analysis involves a number of discrete steps, all of which contribute to the overall re-
liability of the final analytical result: sample collection and shipment, laboratory han-
dling, instrumental analysis, and criteria for internal and external quality control.
From a historical perspective, it is clear that the definition of "satisfactory analyt-
ical method" for lead has been steadily changing as new and more sophisticated equipment be-
comes available and understanding of the hazards of pervasive contamination along the analyti-
cal course increases. The best example of this is the use of the definitive method for lead
analysis, isotope-dilution mass spectrometry in tandem with "ultra-clean" facilities and sam-
pling methods, to demonstrate conclusively not only the true extent of anthropogenic input of
lead to the environment over the years but also the relative limitations of most of the meth-
ods for lead measurement used today.
1.9.1 Determinations of Lead in Biological Media
The low levels of lead in biological media, even in the face of excessive exposure, and
the fact that sampling of such media must be done against a backdrop of pervasive lead contam-
ination, necessitates that samples be carefully collected and handled. Blood lead sampling is
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best done by venous puncture and collection into low-lead tubes after careful cleaning of the
puncture site. The use of finger puncture as an alternative metnod of sampling should be
avoided, if feasible, given the risk of contamination associated with the practice in indus-
trialized areas. While collection of blood onto filter paper enjoyed some popularity in the
past, paper deposition of blood requires special correction for hematrocrit/hemoglobin level.
Urine sample collection requires the use of lead-free containers as well as addition of a
bacteriocide. If feasible, 24-hour sampling is preferred to spot collection. Deciduous teeth
vary in lead content both within and across type of dentition. Thus a specific tooth type
should be uniformly obtained for all study subjects and, if possible, more than a single sam-
ple should be obtained from each subject.
Measurements of lead in blood. Many reports over the years have purported to offer sat-
isfactory analysis of lead in blood and other biological media, often with severe inherent
limitations on accuracy and precision, meager adherence to criteria for accuracy and preci-
sion, and a limited utility across a spectrum of analytical applications. Therefore, it is
only useful to discuss "definitive" and, comparatively speaking, "reference" methods presently
used.
In the case of lead in biological media, the definitive method is isotope-dilution mass
spectrometry (IDMS). The accuracy and unique precision of IDMS arise from the fact that all
manipulations are on a weight basis involving simple procedures, and measurements entail only
lead isotope ratios and not the absolute determinations of the isotopes involved, greatly re-
ducing instrumental corrections and errors. Reproducible results to a precision of one part
in 10 -10 are routine with appropriately designed and competently operated instrumentation.
Although this methodology is still not recognized in many laboratories, it was the first
breakthrough, in tandem with "ultra-clean" procedures and facilities, to definitive methods
for indexing the progressive increase in lead contamination of the environment over the centu-
ries. Given the expense, required level of operator expertise, and time and effort involved
for measurements by IDMS, this methodology mainly serves for analyses that either require
extreme accuracy and precision, e.g., geochronometry, or for the establishment of analytical
reference material for general testing purposes or the validation of other methodologies.
While the term "reference method" for lead in biological media cannot be rigorously ap-
plied to any procedures in popular use, the technique of atomic absorption spectrometry in its
various configurations or the electrochemical method, anodic stripping voltammetry, come clos-
est to meriting the designation. Other methods that are generally applied in metal analyses
are either limited in sensitivity or are not feasible for use on theoretical grounds for lead
analysis.
Atomic absorption spectrometry (AAS) as applied to analysis of whole blood generally in-
volves flame or flameless micromethods. One macromethod, the Hessel procedure, still enjoys
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some popularity. Flame microanalysis, the Delves cup procedure, applied to blood lead appears
to have an operational sensitivity of about 10 (jg Pb/dl blood and a relative precision of
approximately 5 percent in the range of blood lead seen in populations in industrialized
areas. The flameless, or electrothermal, method of AAS enhances sensitivity about 10-fold,
but precision can be more problematical because of chemical and spectral interferences.
The most widely used and sensitive electrochemical method for lead in blood is anodic
stripping voltammetry (ASV). For most accurate results, chemical wet ashing of samples must
be carried out, although this process is time-consuming and requires the use of lead-free rea-
gents. The use of metal exchange reagents has been employed in lieu of the ashing step to li-
berate lead from binding sites, although this substitution is associated with less precision.
For the ashing method, relative precision is approximately 5 percent. In terms of accuracy
and sensitivity, it appears that there are problems at low levels, e.g., 5 pg/dl or below,
particularly if samples contain elevated copper levels.
Lead in plasma. Since lead in whole blood is virtually all confined to the erythrocyte,
plasma levels are quite low and it appears that extreme care must be employed to reliably
measure plasma levels. The best method for such measurement is IDMS, in tandem with ultra-
clean facility use. Atomic absorption spectrometry is satisfactory for comparative analyses
across a range of relatively high whole blood values.
Lead in teeth. Lead measurement in teeth has involved either whole tooth sampling or
analysis of specific regions, such as primary or circumpulpal dentine. In either case, sam-
ples must be solublized after careful surface cleaning to remove contamination; solubilization
is usually accompanied by either wet ashing directly or ashing subsequent to a dry ashing
step.
Atomic absorption spectrometry and anodic stripping have been employed more frequently
for such determinations than any other method. With AAS, the high mineral content of teeth
argues for preliminary isolation of lead via chelation-extraction. The relative precision of
analysis for within-run measurement is around 5-7 percent, with the main determinant of var-
iance in regional assay being the initial isolation step. One change from the usual methods
for such measurement is the ijn situ measurement of lead by X-ray fluorescence spectrometry in
children. Lead measured in this fashion allows observation of en-going lead accumulation, ra-
ther than waiting for exfoliation.
Lead in hair. Hair as an exposure indicator for lead offers the advantages of being non-
invasive and a medium of indefinite stability. However, there is still the crucial problem of
external surface contamination, which is such that it is still not possible to state that any
cleaning protocol reliably differentiates between external and internally deposited lead.
Studies that demonstrate a correlation between increasing hair lead and increasing sever-
ity of a measured effect probably support arguments for hair being an external indicator of
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exposure. It is probably also the case, then, that such measurement, using cleaning protocols
that have not been independently validated, will overstate the relative accumulation of "in-
ternal" hair lead in terms of some endpoint and will also underestimate the relative sensitiv-
ity of changes in internal lead content with exposure. One consequence of this would be, for
example, an apparent threshold for a given effect in terms of hair lead which is significantly
above the actual threshold. Because of these concerns, hair is best used with the simultane-
ous measurement of blood lead.
Lead in urine. Analysis of lead in urine is complicated by the relatively low levels of
the element in this medium as well as the complex mixture of mineral elements present. Urine
lead levels are most useful and also somewhat easier to determine in cases of chelation mobil-
ization or chelation therapy, where levels are high enough to permit good precision and dilu-
tion of matrix interference.
Samples are probably best analyzed by prior chemical wet ashing, using the usual mixture
of acids. Both anodic stripping voltammetry and atomic absorption spectrometry have been ap-
plied to urine analysis, with the latter more routinely used and usually with a chelation/
extraction step.
Lead in other tissues. Bone samples require cleaning procedures for removal of muscle
and connective tissue and chemical solubilization prior to analysis. Methods of analysis are
comparatively limited and it appears that fTameless atomic absorption spectrometry is the
technique of choice.
Lead measurements in bone, iji vivo, have been reported with lead workers, using x-ray
fluorescence analysis and a radioisotopic source for excitation. One problem with this
approach with moderate lead exposure is the detection limit, approximately 20 ppm. Soft organ
analysis poses a problem in terms of heterogeneity of lead distribution within an organ, e.g.
brain and kidney. In such cases, regional sampling or homogenization must be carried out.
Both flame and flameless atomic absorption spectrometry appear to be satisfactory for soft
tissue analysis and are the most widely used.
Quality assurance procedures in lead analyses. In terms of available information, the
major focus in establishing quality control protocols for lead has involved whole blood meas-
urements. Translated into practice, quality control revolves around steps employed within the
laboratory, using a variety of internal checks, and the further reliance on external checks,
such as a formal continuing multi-laboratory proficiency testing program.
Within the laboratory, quality assurance protocols can be divided into start-up and rou-
tine procedures, the former involving establishment of detection limits, within-run and
between-run precision, analytical recovery, and comparison with some reference technique
within or outside the laboratory. The reference method is assumed to be accurate for the par-
ticular level of lead in some matrix at a particular point in time. Correlation with such a
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method at a satisfactory level, however, may simply indicate that both methods are equally
inaccurate but performing with the same level of precision proficiency. More preferable is
the use of certified samples having lead at a level established by the definitive method.
For blood lead, the Centers for Disease Control periodically survey overall accuracy and
precision of methods used by reporting laboratories. In terms of overall accuracy and preci-
sion, one such survey found that anodic stripping voltammetry as well as the Delves cup and
extraction variations of atomic absorption spectrometry performed better than other proce-
dures. These results do not mean that a given laboratory cannot perform better with a partic-
ular technique; rather, such data are of assistance for new facilities choosing among methods.
Of particular value to laboratories carrying out blood lead analysis are the external
quality assurance programs at both the state and federal levels. The most comprehensive pro-
ficiency testing program is that carried out by the Centers for Disease Control, USPHS. This
program actually consists of two subprograms, one directed at facilities involved in lead poi-
soning prevention and screening (Center for Environmental Health) and the other concerned with
laboratories seeking certification under the Clinical Laboratories Improvement Act of 1967 as
well as under regulations of the Occupational Safety and Health Administration's (OSHA) Labor-
atory Improvement Program Office. Overall, the proficiency testing programs have served their
purpose well, judging from the relative overall improvements in reporting laboratories over
the years of the programs' existence. In this regard, OSHA criteria for laboratory certifica-
tion require 8 of 9 samples be correctly analyzed for the previous quarter. This level of
required proficiency reflects the ability of a number of laboratories to actually perform at
this level.
1.9.2 Determination of Erythrocyte Porphyrin (Free Erythrocyte Protoporphyrin. Zinc
Protoporphyrin)
With lead exposure, there is an accumulation of erythrocyte protoporphyrin IX, owing to
impaired placement of divalent iron to form heme. Divalent zinc occupies the place of the na-
tive iron. Depending upon the method of analysis, either metal-free erythrocyte porphyrin or
zinc protoporphyrin (ZPP) is measured, the former arising from loss of zinc in the chemical
manipulation. Virtually all methods now in use for EP analysis exploit the ability of the
porphyrin to undergo intense fluorescence when excited by ultraviolet light. Such fluoro-
metric methods can be further classified as wet chemical micromethods or direct measuring
fluorometry using the hematof1uorometer. Owing to the high sensitivity of such measurement,
relatively small blood samples are required, with liquid samples or blood collected on filter
paper.
The most common laboratory or wet chemical procedures now in us,e represent variations of
several common chemical procedures: (1) treatment of blood samples with a mixture of ethyl
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acetate/acetic acid followed by a repartitioning into an inorganic acid medium, or (2) solu-
bilization of a blood sample directly into a detergent/buffer solution at a high dilution.
Quantification has been done using protoporphyrin, coproporphyrin, or zinc protoporphyrin IX
plus pure zinc ion. The levels of precision for these laboratory techniques vary somewhat
with the specifics of analysis. The Piomelli method has a coefficient of variation of 5
percent, while the direct ZPP method using buffered detergent solution is higher and more
variable.
The recent development of the hematofluorometer has made it possible to carry out EP mea-
surements in high numbers, thereby making population screening feasible. Absolute calibration
is necessary and requires periodic adjustment of the system using known concentrations of EP
in reference blood samples. Since these units are designed for oxygenated blood, i.e.,
capillary blood, use of venous blood requires an oxygenation step, usually a moderate shaking
for several minutes. Measurement of low or moderate levels of EP can be affected by inter-
ference with bilirubin. Competently employed, the hematofluorometer appears to be reasonably
precise, showing a total coefficient of variation of 4.11-11.5 percent. While the comparative
accuracy of the unit has been reported to be good relative to the reference wet chemical
technique, a very recent study has shown that commercial units carry with them a significant
negative bias, which may lead to false negatives in subjects having only moderate EP
elevation. Such a bias in accuracy has been difficult to detect in existing EP proficiency
testing programs. It appears that, by comparision to wet methods, the hematofluorometer
should be restricted to field use rather than becoming a substitute in the laboratory fof
chemical measurement, and field use should involve periodic split-sample comparison testing
with the wet method.
1.9.3 Measurement of Urinary Coproporphyrin
Although EP measurement has largely supplanted the use of urinary coproporphyrin analysis
(CP-U) to monitor excessive lead exposure in humans, this measurement is still of value in
that it reflects active intoxication. The standard analysis is a fluorometric technique
whereby urine samples are treated with buffer, and an oxidant (iodine) is added to generate CP
from its precursor. The CP-U is then partitioned into ethyl acetate and re-extracted with
dilute hydrochloric acid. The working curve is linear below 5 pg CP/dl urine.
1.9.4 Measurement of Delta-Ami no!evulim'c Acid Dehydrase Activity
Inhibition of the activity of the erythrocyte enzyme, delta-aminolevulinic acid dehydrase
(ALA-D), by lead is the basis for using such activity in screening for excessive lead expo-
sure. A number of sampling and sample handling precautions attend such analysis. Since zinc
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(II) ion will offset the degree of activity inhibition by lead, blood collecting tubes must
have extremely low zinc content. This essentially rules out the use of rubber-stoppered blood
tubes. Enzyme stability is such that the/ activity measurement is best carried out within 24
hours of blood collection. Porphobilinogen, the product of enzyme action, is light-labile and
requires the assay be done in restricted light. Various procedures for ALA-D measurement are
based on measurement of the level of the chromophoric pyrrole (approximately 555 nm) formed by
condensation of the porphobilinogen with p-dimethylaminobenzaldehyde.
In the European Standardized Method for ALA-D activity determination, blood samples are
hemolyzed with water, ALA solution added, followed by incubation at 37°C, and the reaction
terminated by a solution of mercury (II) in trichloroacetic acid. Filtrates are treated with
modified Ehrlich's reagent (p-dimethylaminobenzaldehyde) in trichloroacetic/perchloroacetic
acid mixture. Activity is quantified in terms of micromoles ALA/min/liter erythrocytes.
One variation in the above procedure is the initial use of a thiol agent, such as dithio-
threotol, to reactivate the enzyme, giving a measure of the full native activity of the
enzyme. The ratio of activated/unactivated activity vs. blood lead levels accomodates genetic
differences between individuals.
1.9.5 Measurement of Delta-Ami no!evulinic Acid in Urine and Other Media
Levels of delta-aminolevulinic acid (6-ALA) in urine and plasma increase with elevated
lead exposure. Thus, measurement of this metabolite, generally in urine, provides an index of
the level of lead exposure. ALA content of urine samples (ALA-U) is stable for about two
weeks or more with sample acidification and refrigeration. Levels of ALA-U are adjusted for
urine density or expressed per unit creatinine. If feasible, 24-hour collection is more
desirable than spot sampling.
Virtually all the various procedures for ALA-U measurement employ preliminary isolation
of ALA from the balance of urine constituents. In one method, further separation of ALA from
the metabolite aminoacetone is done. Aminoacetone can interfere with colorimetric measure-
ment. ALA is recovered, condensed with a beta-dicarbonyl compound, e.g., acetyl acetone, to
yield a pyrrole intermediate. This intermediate is then reacted with p-dimethylaminobenzalde-
hyde in perchloric/acetic acid, followed by colorimetric reading at 553 nm. In one variation
of the basic methodology, ALA is condensed with ethyl acetoacetate directly and the resulting
pyrrole extracted with ethyl acetate. Ehrlich's reagent is then added as in other procedures
and the resulting chromophore measured spectrophotometrically.
Measurement of ALA in plasma is much more difficult than in urine, since plasma ALA is at
nanogram/ni Hiter levels. In one gas-liquid chromatographic procedure, ALA is isolated from
plasma, reacted with acetyl acetone and partitioned into a solvent that also serves for pyro-
lytic methylation of the involatile pyrrole in the injector port of the chromatograph, making
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the derivative more volatile. For quantification, an interval standard, 6-amino-5-oxohexanoic
acid, is used. While the method is more involved, it is more specific than the older colori-
metric technique.
1.9.6 Measurement of Pyrimidine-5'-Nuc1eotidase Activity
Erythrocyte pyrimidine-5'-nucleotidase (Py5N) activity is inhibited with lead exposure.
Presently two different methods are used for assaying the activity of this enzyme. The older
method is quite laborious in time and effort, whereas the more recent approach is shorter but
uses radioisotopes and radiometric measurement.
In the older method, heparinized venous blood is filtered through cellulose to separate
erythrocytes from platelets and leukocytes. Cells are then freeze-fractured and the hemoly-
sates dialyzed to remove nucleotides and other phosphates. This dialysate is then Incubated
in the presence of a nucleoside monophosphate and cofactors, the enzyme reaction being termi-
nated by treatment with trichloroacetic acid. The inorganic phosphate isolated from added
substrate is measured colorimetrically as the phosphomolybdic acid complex.
In the radiometric assay, hemolysates obtained as before are incubated with pure C-CMP.
By addition of a barium hydroxide/zinc sulfate solution, proteins and unreacted nucleotide are
precipitated, leaving labeled cytidine in the supernatant. Aliquots are measured for C ac-
tivity in a liquid scintillation counter. This method shows a good correlation with the ear-
lier technique.
1.10 METABOLISM OF LEAD
Toxicokinetic parameters of lead absorption, distribution, retention, and excretion con-
necting external environmental lead exposure to various adverse effects are discussed in this
section. Also considered are various influences on these parameters, e.g., nutritional
status, age, and stage of development.
A number of specific issues in lead metabolism by animals and humans merit special focus
and these include:
1. How does the developing organism from gestation to maturity differ from the
adult in toxicokinetic response to lead intake?
2. What do these differences in lead metabolism portend for relative risk for
adverse effects?
3. What are the factors, that significantly change the toxicokinetic parameters in
ways relevant to assessing health risk?
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4. How do the various interrelationships among body compartments for lead trans-
late to assessment of internal exposure and changes in internal exposure?
1.10.1 Lead Absorption in Humans and Animals
The amounts of lead entering the bloodstream via various routes of absorption are influ-
enced not only by the levels of the element in a given medium but also by various physical and
chemical parameters and specific host factors, such as age and nutritional status.
Respiratory absorption of lead. The movement of lead from ambient air to the blood-
stream is a two-part process: deposition of some fraction of inhaled air lead in the deeper
part of the respiratory tract and absorption of the deposited fraction. For adult humans, the
deposition rate of particulate airborne lead as likely encountered by the general population
is around 30-50 percent, with these rates being modified by such factors as particle size and
ventilation rates. It also appears that essentially all of the lead deposited in the lower
respiratory tract is absorbed, so that the overall absorption rate is governed by the deposi-
tion rate, i.e., approximately 30-50 percent. Autopsy results showing no lead accumulation in
the lung indicate quantitative absorption of deposited lead.
All of the available data for lead uptake via the respiratory tract in humans have been
obtained with adults. Respiratory uptake of lead in children, while not fully quantifiable,
appears to be comparatively greater on a body weight basis, compared to adults. A second fac-
tor influencing the relative deposition rate in children has to do with airway dimensions.
One report has estimated that the 10-year-old child has a deposition rate 1.6- to 2.7-fold
higher than the adult on a weight basis.
It appears that the chemical form of the lead compound inhaled is not a major determinant
of the extent of alveolar absorption of lead. While experimental animal data for quantitative
assessment of lead deposition and absorption for the lung and upper respiratory tract are lim-
ited, available information from the rat, rabbit, dog, and nonhuman primate support the find-
ings that respired lead in humans is extensively and rapidly absorbed.
Gastrointestinal absorption of lead. Gastrointestinal absorption of lead mainly involves
lead uptake from food and beverages as well as lead deposited in the upper respiratory tract,
which is eventually swallowed. It also includes ingestion of non-food material, primarily in
children via normal mouthing activity and pica. Two issues of concern with lead uptake from
the gut are the comparative rates of such absorption in developing vs. adult organisms,
including humans, and how the relative bioavailability of lead affects such uptake.
By use of metabolic balance and isotopic (radioisotope or stable isotope) studies, var-
ious laboratories have provided estimates of lead absorption in the human adult on the order
of 10-15 percent. This rate can be significantly increased under fasting conditions to 45
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percent, compared to lead ingested with food. The latter figure also suggests that beverage
lead is absorbed to a greater degree since much beverage ingestion occurs between meals
The relationship of the chemical/biochemical form of lead in the gut to absorption rate
has been studied, although interpretation is complicated by the relatively small amounts given
and the presence of various components in food already present in the gut. In general, how-
ever, chemical forms of lead or their incorporation into biological matrices seems to have a
minimal impact on lead absorption in the human gut. Several studies have focused on the ques-
tion of differences in gastrointestinal absorption rates for lead between children and adults
It would appear that such rates for children are considerably higher than for adults: 10-15
percent for adults vs. approximately 50 percent for children. Available data for the absorp-
tion of lead from non-food items such as dust and dirt on hands are limited, but one study has
estimated a figure of 30 percent. For paint chips, a value of about 17 percent has been esti-
mated.
Experimental animal studies show that, like humans, the adult absorbs much less lead from
the gut than the developing animal. Adult rats maintained on ordinary rat chow absorb 1 per-
cent or less of the dietary lead. Various animal species studies make it clear that the new-
born absorbs a much greater amount of lead than the adult, supporting studies showing this age
dependency in humans. Compared to an absorption rate of approximately 1 percent in adult
rats, the rat pup has a rate 40-50 times greater. Part, but not most, of the difference can
be ascribed to a difference in dietary composition. In nonhuman primates, infant monkeys
absorb 65-85 percent of lead from the gut, compared to 4 percent for the adults.
The bioavailability of lead in the gastrointestinal (GI) tract as a factor in its absorp-
tion has been the focus of a number of experimental studies. These data show that: (l) lead
in a number of forms is absorbed about equally, except for the sulfide; (2) lead in dirt and
dust and as different chemical forms is absorbed at about the same rate as pure lead salts
added to the diet; (3) lead in paint chips undergoes significant uptake from the gut; and
4) in some cases, physical size of particulate lead can affect the rate of GI absorption
Percutaneous absorption of lead. Absorption of inorganic lead compounds through the skin
is of much less significance than through the respiratory and gastrointestinal routes. This
is in contrast to the case with lead alkyls (See Section 1.10.6). One recent study usina
human volunteers and Pb-labeled lead acetate showed that under normal conditions, absorp-
tion approaches 0.06 percent.
Transplacental transfer of lead. Lead uptake by the human and animal fetus readily
occurs, such transfer going on by the 12th week of gestation in humans, with increasing fetal
uptake throughout development. Cord blood contains significant amounts of lead, correlating
with but somewhat lower than maternal blood lead levels. Evidence for such transfer, besides
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lead content of cord blood, includes fetal tissue analyses and reduction in maternal blood
lead during pregnancy. There also appears to be a seasonal effect on the fetus, summer-born
children showing a trend toward higher blood lead levels than those born in the spring.
1.10.2 Distribution of Lead in Humans and Animals
In this subsection, the distributional characteristics of lead in various portions of the
body—blood, soft tissue, calcified tissue, and the "chelatable" or potentially toxic body
burden—are discussed as a function of such variables as exposure history and age.
1.10.2.1 Lead in Blood. More than 99 percent of blood lead is associated with the erythro-
cyte in humans under steady-state conditions, but it is the very small fraction transported in
plasma and extracellular fluid that provides lead to the various body organs. Most (~ 50 per-
cent) of erythrocyte lead is bound within the cell, primarily associated with hemoglobin (par-
ticularly HbA2), with approximately 5 percent bound to a 10,000-dalton fraction, 20 percent to
a heavier molecule, and 25 percent to lower weight species.
Whole blood lead in daily equilibrium with other compartments in adult humans appears to
have a biological half-time of 25-28 days and comprises about 1.9 mg in total lead content.
Human blood lead responds rather quickly to abrupt changes in exposure. With increased lead
intake, blood lead achieves a new value in approximately 40-60 days, while a decrease in expo-
sure may be associated with variable new blood values, depending upon the exposure history.
This dependence presumably reflects lead resorption from bone. With age, furthermore, there
appears to be little change in blood lead during adulthood. Levels of lead in blood of chil-
dren tend to show a peaking trend at 2-3 years of age, probably due to mouthing activity, fol-
lowed by a decline. In older children and adults, levels of lead are sex-related, females
showing lower levels than men even at comparable levels of exposure.
In plasma, lead is virtually all bound to albumin and only trace amounts to high weight
globulins. It is not possible to state which binding form constitutes an "active" fraction
for movement to tissues. The most recent studies of the erythrocyte-plasma relationship in
humans indicate that there is an equilibrium between these blood compartments, such that
levels in plasma rise with levels in whole blood.
1.10.2.2 Lead Levels in Tissues. Of necessity, various relationships of tissue lead to expo-
sure and toxicity in humans must generally be obtained from autopsy samples. Limitations on
such data include questions of how samples represent lead behavior in the living population,
particularly with reference to prolonged illness and disease states. The adequate characteri-
zation of exposure for victims of fatal accidents is a problem, as is the fact that such stud-
ies are cross-sectional in nature, with different age groups assumed to have had similar ex-
posure in the past.
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Soft tissues. After age 20, most soft tissues in humans do not show age-related changes
in contrast to bone. Kidney cortex shows increase in lead with age which may be associated
with formation of nuclear inclusion bodies. Absence of lead accumulation in most soft tissues
is due to a turnover rate for lead which is similar to that in blood.
Based on several autopsy studies, it appears that soft tissue lead content for individ-
uals not occupationally exposed is generally below 0.5 ng/g wet weight, with higher values for
aorta and kidney cortex. Brain tissue lead level is generally below 0.2 ppm wet weight with
no change with increasing age, although the cross-sectional nature of these data would make
changes in low brain lead levels difficult to discern. Autopsy data for both children and
adults indicate that lead is selectively accumulated in the hippocampus, a finding that is
also consistent with the reginal distribution in experimental animals.
Comparisons of lead levels in soft tissue autopsy samples from children with results from
adults indicate that such values are lower in infants than in older children, while children
aged 1-16 years had levels comparable to adult women. In one study, lead content of brain re-
gions did not materially differ for infants and older children compared to adults. Complicat-
ing these data somewhat are changes in tissue mass with age, although such changes are less
than for the skeletal system.
Subcellular distribution of lead in soft tissue is not uniform, with high amounts of lead
being sequestered in the mitochondria and nucleus. Nuclear accumulation is consistent with
the existence of lead-containing nuclear inclusions in various species and a large body of
data demonstrating the sensitivity of mitochondria to injury by lead.
Mineralizing tissue. Lead becomes localized and accumulates in human calcified tissues,
i.e., bones and teeth. This accumulation in humans begins with fetal development and contin-
ues to approximately 60 years of age. The extent of lead accumulation in bone ranges up to
200 mg in men ages 60-70 years, while in women lower values have been measured. Based upon
various studies, approximately 95 percent of total body lead is lodged in the bones of human
adults, with uptake distributed over trabecular and compact bone. In the human adult, bone
lead is both the most inert and largest body pool, and accumulation can serve to maintain el-
evated blood lead levels years after exposure, particularly occupational exposure, has ended.
Compared to the human adult, 73 percent of body lead is lodged in the bones of children
which is consistent with other information that the skeletal system of children is more meta-
bolically active than in the adult. While the increase in bone lead across childhood is mod-
est, about 2-fold if expressed as concentration, the total accumulation rate is actually 80-
fold, taking into account a 40-fold increase in skeletal mass. To the extent that some sig-
nificant fraction of total bone lead in children and adults is relatively labile, it is more
appropriate in terms of health risk for the whole organism to consider the total accumulation
rather than just changes in concentration.
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The traditional view that the skeletal system was a "total" sink for body lead (and by
implication a biological safety feature to permit significant exposure in industrialized popu-
lations) never did accord with even older information on bone physiology, e.g., bone remodel-
ling, and is now giving way to the view that there are at least several bone compartments for
lead, with different mobility profiles. It would appear, then, that "bone lead" may be more
of an insidious source of long-term internal exposure than a sink for the element. This
aspect of the issue is summarized more fully in the next section. Available information from
studies of such subjects as uranium miners and human volunteers ingesting stable isotopes in-
dicates that there is a relatively inert bone compartment for lead, having a half-time of sev-
eral decades, and a rather labile compartment which permits an equilibrium between bone and
tissue lead.
Tooth lead also increases with age at a rate proportional to exposure and roughly propor-
tional to blood lead in humans and experimental animals. Dentine lead is perhaps the most re-
sponsive component of teeth to lead exposure since it is laid down from the time of eruption
until shedding. It is this characteristic which underlies the utility of dentine lead levels
in assessing long-term exposure.
Chelatable lead. Mobile lead in organs and systems is potentially more active toxicolog-
ically in terms of being available to biological sites of action. Hence, this fraction of
total body lead burden is a more significant predictor of imminent toxicity. In reality,
direct measurement of such a fraction in human subjects would not be possible. In this
regard, "chelatable" lead, measured as the extent of plumburesis in response to administration
of a chelating agent, is now viewed as the most useful probe of undue body burden in childte,
and adults.
A quantitative description of the inputs to the body lead fraction that is chelant-
mobilizable is difficult to fully define, but it most likely includes a labile lead compart-
ment within bone as well as in soft tissues. Support for this view includes: (1) the age de-
pendency of chelatable lead, but not lead in blood or soft tissues; (2) evidence of removal of
bone lead in chelation studies with experimental animals; (3) iji vitro studies of lead mobili-
zation in bone organ explants under closely defined conditions; (4) tracer modelling estimates
in human subjects; and (5) the complex nonlinear relationship of blood lead and lead intake
through various media. Data for children and adults showing a logarithmic relationship of
chelatable lead to blood lead and the phenomenon of "rebound" in blood lead elevation after
chelation therapy regimens (without obvious external re-exposure) offer further support.
Animal studies. Animal studies have been of help in sorting out some of the relation-
ships of lead exposure to iji vivo distribution of the element, particularly the impact of
skeletal lead on whole body retention. In rats, lead administration results in an initial in-
crease in soft tissues, followed by loss from soft tissue via excretion and transfer to bone.
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Lead distribution appears to be relatively independent of dose. Other studies have shown that
lead loss from organs follows first-order kinetics except for bone, and the skeletal system in
rats and mice is the kinetically rate-limiting step in whole-body lead clearance.
The neonatal animal seems to retain proportionally higher levels of tissue lead compared
to the adult and manifests slow decay of brain lead levels while showing a significant decline
over time in other tissues. This appears to be the result of enhanced lead entry into the
brain because of a poorly developed blood-brain barrier system as well as enhanced body reten-
tion of lead by young animals.
The effects of such changes as metabolic stress and nutritional status on body redistri-
bution of lead have been noted. Lactating mice, for example, are known to demonstrate tissue
redistribution of lead, specifically bone lead resorption with subsequent transfer of both
lead and calcium from mother to pups.
1.10.3 Lead Excretion and Retention in Humans and Animals
Human studies. Dietary lead in humans and animals that is not absorbed passes through
the gastrointestinal tract and is eliminated with feces, as is the fraction of air lead that
is swallowed and not absorbed. Lead entering the bloodstream and not retained is excreted
through the renal and GI tracts, the latter via biliary clearance. The amounts excreted
through these routes are a function of such factors as species, age, and exposure character-
istics.
Based upon the human metabolic balance data and isotope excretion findings of various in-
vestigators, it appears that short-term lead excretion in adult humans amounts to 50-60 per-
cent of the absorbed fraction, with the balance moving primarily to bone and some fraction
(approximately half) of this stored amount eventually being excreted. This overall retention
figure of 25 percent necessarily assumes that isotope clearance reflects that for body lead in
all compartments. The rapidly excreted fraction has a biological half-time of 20-25 days,
similar to that for lead removal from blood. This similarity indicates a steady rate of lead
clearance from the body. In terms of partitioning of excreted lead between urine and bile
one study indicates that the biliary clearance is about 50 percent that of renal clearance.
Lead is accumulated in the human body with age, mainly in bone, up to around 60 years of
age, when a decrease occurs with changes in intake as well as in bone mineral metabolism. As
noted earlier, the total amount of lead in long-term retention can approach 200 mg, and even
much higher in the case of occupational exposure. This corresponds to a lifetime average
retention rate of 9-10 ug Pg/day. Within shorter time frames, however, retention will vary
considerably due to such factors as development, disruption in the individuals' equilibrium
with lead intake, and the onset of such states as osteoporosis.
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The age dependency of lead retention/excretion in humans has not been well studied, but
most of the available information indicates that children, particularly infants, retain a sig-
nificantly higher amount of lead. While autopsy data indicate that pediatric subjects at iso-
lated points in time actually have a lower fraction of body lead lodged in bone, a full under-
standing of longer-term retention over childhood must consider the exponential growth rate oc-
curring in a child's skeletal system over the time period for which bone lead concentrations
have been gathered. This parameter itself represents a 40-fold mass increase. This signifi-
cant skeletal growth rate has an impact on an obvious question: if children take in more lead
on a body weight basis than adults, absorb and retain more lead than adults, and show only
modest elevations in blood lead compared to adults in the face of a more active skeletal sys-
tem, where does the lead go? A second factor is the assumption that blood lead in children
relates to body lead burden in the same quantitative fashion as in adults, an assumption that
remains to be adequately proven.
Animal studies. In rats and other experimental animals, both urinary and fecal excretion
appear to be important routes of lead removal from the organism; the relative partitioning
between the two modes is species- and dose-dependent. With regard to species differences,
biliary clearance of lead in the dog is but 2 percent of that for the rat, while such excre-
tion in the rabbit is 50 percent that of the rat.
Lead movement from laboratory animals to their offspring via milk constituents is a route
of excretion for the mother as well as an exposure route for the young. Comparative studies
of lead retention in developing vs. adult animals, e.g., rats, mice, and non-human primates,
make it clear that retention is significantly greater in the young animal. These observations
support those studies showing greater lead retention in children. Some recent data indicate
that a differential retention of lead in young rats persists into the post-weaning period,
calculated as either uniform dosing or uniform exposure.
1.10.4 Interactions of Lead with Essential Metals and Other Factors
Toxic elements such as lead are affected in their toxicokinetic or toxicological behavior
by interactions with a variety of biochemical factors such as nutrients.
Human studies. In humans the interactive behavior of lead and various nutritional fac-
tors is expressed most significantly in young children, with such interactions occurring
against a backdrop of rather widespread deficiencies in a number of nutritional components.
Various surveys have indicated that deficiency in iron, calcium, zinc, and vitamins are wide-
spread among the pediatric population, particularly the poor. A number of reports have docu-
mented the association of lead absorption with suboptimal nutritional states for iron and cal-
cium, reduced intake being associated with increased lead absorption.
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Animal studies. Reports of lead-nutrient interactions in experimental animals have
generally described such relationships for a single nutrient, using relative absorption or
tissue retention in the animal to index the effect. Most of the recent data are for calcium,
iron, phosphorus, and vitamin D. Many studies have established that diminished dietary cal-
cium is associated with increased blood and soft tissue lead content in such diverse species
as the rat, pig, horse, sheep, and domestic fowl. The increased body burden of lead arises
from both increased GI absorption and increased retention, indicating that the lead-calcium
interaction operates at both the gut wall and within body compartments. Lead appears to tra-
verse the gut via both passive and active transfer, involves transport proteins normally oper-
ating for calcium transport, and is taken up at the site of phosphorus, not calcium, absorp-
tion.
Iron deficiency is associated with an increase in lead of tissues and increased toxicity,
an effect which is expressed at the level of lead uptake by the gut wall. JTI vitro studies
indicate an interaction through receptor binding competition at a common site. This probably
involves iron-binding proteins. Similarly, dietary phosphate deficiency enhances the extent
of lead retention and toxicity via increased uptake of lead at the gut wall, both lead and
phosphate being absorbed at the same site in the small intestine. Results of various studies
of the resorption of phosphate along with lead as one further mechanism of elevation of tissue
lead have not been conclusive. Since calcium plus phosphate retards lead absorption to a
greater degree than simply the sums of the interactions, it has been postulated that an insol-
uble complex of all these elements may be the basis of this retardation.
Unlike the inverse relationship existing for calcium, iron, and phosphate vs. lead
uptake, vitamin D levels appear to be directly related to the rate of lead absorption from the
GI tract, since the vitamin stimulates the same region of the duodenum where lead is absorbed.
A number of other nutrient factors are known to have an interactive relationship with lead:
1. Increases in dietary lipids increase the extent of lead absorption, with the
extent of the increase being highest with polyunsaturates and lowest with satu-
rated fats, e.g., tristearin.
2. The interactive relationship of lead and dietary protein is not clearcut, and
either suboptimal or excess protein intake increases lead absorption.
3. Certain milk components, particularly lactose, also greatly enhance lead ab-
sorption in the nursing animal.
4. Zinc deficiency promotes lead absorption, as does reduced dietary copper.
1.10.5 Interrelationships of Lead Exposure with Exposure Indicators and Tissue Lead Burdens
There are three issues involving lead toxicokinetics which bear importantly on the char-
acterization of relationships between lead exposure and its toxic effects: (1) the temporal
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characteristics of internal indices of lead exposure; (2) the biological aspects of the rela-
tionship of lead in various environmental media to various indicators of internal exposure;
and (3) the relationship of various internal indicators of exposure to target tissue lead bur-
dens.
Temporal characteristics of internal indicators of lead exposure. The biological half-
time for newly absorbed lead in blood appears to be of the order of weeks or several months,
so that this medium reflects relatively recent exposure. If recent exposure is fairly repre-
sentative of exposure over a considerable period of time, e.g., exposure of lead workers, then
blood lead is more useful than for cases where exposure is intermittent across time, as is
often the case of pediatric lead exposure. Accessible mineralized tissue, such as shed teeth,
extend the time frame back to years of exposure, since teeth accumulate lead with age and as a
function of the extent of exposure. Such measurements are, however, retrospective in nature,
in that identification of excessive exposure occurs after the fact and thus limits the possi-
bility of timely medical intervention, exposure abatement, or regulatory policy concerned with
ongoing control strategies.
Perhaps the most practical solution to the dilemma posed by both tooth and blood lead
analyses is in situ measurement of lead in teeth or bone during the time when active accumu-
lation occurs, e.g., in 2 to 3-year-old children. Available data using X-ray fluorescence
analysis suggest that such approaches are feasible and can be reconciled with such issues as
acceptable radiation hazard risk to subjects.
Biological aspects of external exposure-internal indicator relationships. It is clear
from a reading of the literature that the relationship of lead in relevant media for human ex-
posure to blood lead is curvilinear when viewed over a relatively broad range of blood lead
values. This implies that the unit change in blood lead per unit intake of lead in some
medium varies across this range of exposure, with comparatively smaller blood lead changes as
internal exposure increases.
Given our present knowledge, such a relationship cannot be taken to mean that body uptake
of lead is proportionately lower at higher exposure, for it may simply mean that blood lead
becomes an increasingly unreliable measure of target tissue lead burden with increasing expo-
sure. While the basis of the curvilinear relationship remains to be identified, available an-
imal data suggest that it does not reflect exposure-dependent absorption or excretion rates.
Internal indicator-tissue lead relationships. In living human subjects, it is not possi-
ble to determine directly tissue lead burdens or how these relate to adverse effects in target
tissues; some accessible indicator, e.g., lead in a medium such as blood or a biochemical sur-
rogate of lead such as EP, must be employed. While blood lead still remains the only practi-
cal measure of excessive lead exposure and health risk, evidence continues to accumulate that
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such an index has limitations in either reflecting tissue lead burdens or changes in such tis-
sues with changes in exposure.
At present, the measurement of plumburesis associated with challenge by a single dose of
a lead chelating agent such as CaNa-EDTA is considered the best indicator of the mobile, po-
tentially toxic fraction of body lead. Chelatable lead is logarithmically related to blood
lead, such that incremental increase in blood lead is associated with an increasingly larger
increment of mobilizable lead. The problems associated with this logarithmic relationship may
be seen in studies of children and lead workers in whom moderate elevation in blood lead can
disguise levels of mobile body lead. This reduces the margin of protection against severe in-
toxication. The biological basis of the logarithmic relationship between Chelatable lead and
blood lead rests, in large measure, with the existence of a sizable bone lead compartment that
is mobile enough to undergo chelation removal and, hence, potentially mobile enough to move
into target tissues.
Studies of the relative mobility of Chelatable lead over time indicate that, in former
lead workers, removal from exposure leads to a protracted washing out of lead (from bone re-
sorption of lead) to blood and tissues, with preservation of a bone burden amenable to subse-
quent chelation. Studies with children are inconclusive, since the one investigation directed
to this end employed pediatric subjects who all underwent chelation therapy during periods of
severe lead poisoning. Animal studies demonstrate that changes in blood lead with increasing
exposure do not agree with tissue uptake in a time-concordant fasion, nor does decrease in
blood lead with reduced exposure signal a similar decrease in target tissue, particularly in
the brain of the developing organism.
1.10.6 Metabolism of Lead Alkyls
The lower alkyl lead components used as gasoline additives, tetraethyl lead (TEL) and
tetramethyl lead (TML), may themselves poise a toxic risk to humans. In particular, there is
among children a problem of sniffing leaded gasoline.
Absorption of lead alkyls in humans and animals. Human volunteers inhaling labeled TEL
and TML show lung deposition rates for the lead alkyls of 37 and 51 percent, respectively,
values which are similar to those for particulate inorganic lead. Significant portions of
these deposited amounts were eventually absorbed. Respiratory absorption of organolead bound
to particulate matter has not been specifically studied as such.
While specific data for the GI absorption of lead alkyls in humans and animals are not
available, their close similarity to organotin compounds, which are quantitatively absorbed
would argue for extensive GI absorption. In contrast to inorganic lead salts, the lower lead
alkyls are extensively absorbed through the skin and animal data show lethal effects-with per-
cutaneous uptake as the sole route of exposure.
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Biotransformation and tissue distribution of lead alkyls. The lower lead alkyIs TEL and
TML undergo monodealkylation in the liver of mammalian species via the P-450-dependent mono-
oxygenase enzyme system. Such transformation is very rapid. Further transformation involves
conversion to the dialkyl and inorganic lead forms, the latter accounting for the effects on
heme biosynthesis and erythropoiesis observed in alkyl lead intoxication. Alykl lead is
rapidly cleared from blood, shows a higher partitioning into plasma than inorganic lead with
triethyl lead clearance being more rapid than the methyl analog.
Tissue distribution of alkyl lead in humans and animals primarily involves the trialkyl
metabolites. Levels are highest in liver, followed by kidney, then brain. Of interest is the
fact that there are detectable amounts of trialkyl lead from autopsy samples of human brain
even in the absence of occupational exposure. In humans, there appear to be two tissue com-
partments for triethyl lead, having half-times of 35 and 100 days.
Excretion of lead alkyls. With alkyl lead exposure, excretion of lead through the renal
tract is the main route of elimination. The chemical forms being excreted appear to be
species-dependent. In humans, trialkyl lead in workers chronically exposed to alkyl lead is a
minor component of urine lead, approximately 9 percent.
1.11 ASSESSMENT OF LEAD EXPOSURES AND ABSORPTION IN HUMAN POPULATIONS
Chapter 11 describes the effect of exposure of human populations to lead in their en-
vironment. The effect discussed is a change in an internal exposure index that follows changes
in external exposures. The index of internal lead exposure most frequently cited is blood
lead levels, but other indices such as levels of lead in tooth and bone are also presented.
Blood lead level estimates the body's recent exposure to environmental lead, while teeth and
bone lead levels represent cumulative exposures.
Measurement of lead in blood has been accompTished via a succession of analytical proce-
dures over the years. With these changes in technology there has been increasing recognition
of the importance of controlling for contamination in the sampling and analytical procedures.
These advances as well as the institution of external quality control programs have resulted
in markedly improved analytic results. A generalized improvement in analytic results across
many laboratories occurred during Federal Fiscal Years 1977-1979.
The main discussion of scientific evidence in Chapter 11 is structured to achieve four
main objectives:
(1) Elucidate patterns of absorbed lead in U.S. populations and identify important
demographic covariates.
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(2) Characterize relationships between external and internal exposures by exposure
medium.
(3) Define the relative contributions of various sources of lead in the environment
to total internal exposure.
(4) Identify specific sources of lead which result in increased internal exposure
levels.
A question of major interest in understanding environmental pollutants is the extent to
which current ambient exposures exceed background levels. Ancient Nubians samples (dated
3300-2900 B.C.) averaged 0.6 ug lead/g for bone and 0.9 \ig lead/g for teeth. More recent
Peruvian Indian samples (12th Century) had teeth lead levels of 13.6 ug/g. Contemporary
Alaskan Eskimo samples had a mean of 56.0 ug/g, while Philadelphia samples had a mean of 188.3
ug/g. These data suggest an increasing pattern of lead absorption.
Several studies have looked at the blood lead levels in current remote populations such
as natives in a remote (far from industrialized regions) section of Nepal where the lead con-
tent of the air samples proved to be less than the detection limit, 0.004 ug/m (Piomelli et
al., 1980). The geometric mean blood lead for this population was 3.4 ug/dl. Adult males had
a geometric mean of 3.8 ug/dl and adult females, 2.9 ug/dl. Children had a geometric mean
blood lead of 3.5
1.11.1 Levels of Lead and Demographic Covariates in U.S. Populations
The National Center for Health Statistics has provided the best currently available pic-
ture of blood lead levels among United States residents as part of the second National Health
and Nutrition Examination Study (NHANES II) conducted from February, 1976 to February, 1980
(Mahaffey et al., 1980; McDowell et al., 1981; Annest et al., 1982). The national estimates
are based on 9933 persons whose blood lead levels ranged from 2.0 to 66.0 ug/dl. The median
blood lead for the entire U.S. population is 13.0 ug/dl.
Age appears to be one of the most important demographic covariates of blood lead levels.
Blood lead levels in children are generally higher than those in non-occupational ly exposed
adults. Childred aged 24-36 months tend to have the highest blood lead levels. The age
trends in blood lead levels for children under 10 years old, as seen in three studies are pre-
sented in Figure 1-13. Blood l.ead levels in non-occupational ly exposed adults may increase
slightly with age due to skeletal lead accumulation.
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40
30
26
O
I
20
IS
10
IDAHO STUDY
NEW YORK SCREENING • BLACKS
NEW YORK SCREENING • WHITES
NEW YORK SCREENING • HISPANICS
NHANES II STUDY • BLACKS
NHANES II STUDY • WHITES
I I I I
466
AGE IN YEARS
10
Figure 1-13. Geometric mean blood lead levels by race and age for younger children
in the NHANES II study, and the Kellogg/Silver Valley and New York Childhood
Screening Studies.
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Sex has a differential impact on blood lead levels depending on age. No significant dif-
ference exists between males and females less than seven years of age. Males above the age of
seven generally have higher blood lead levels than females. Race also plays a role, in that
blacks have higher blood lead levels than either whites or Hispanics. The reason for this has
yet to be totally disentangled from exposure.
Blood lead levels also seem to increase with degree of urbanization. Data from NHANES II
show that blood lead levels in the United States, averaged from 1976 to 1980, increase from a
geometric mean of 11.9 jjg/dl in rural populations to 12.8 pg/dl in urban populations less than
one million and increase again to 14.0 ug/dl in urban populations of one million or more.
(see Table 1-9).
Recent U.S. blood lead levels show that a downward has trend occurred consistently across
race, age, and geographic location. The downward pattern commenced in the early part of the
1970's and has continued into 1980. The downward trend has occurred from a shift in the en-
tire distribution and not just via a truncation in high blood lead levels. This consistency
suggests a general causative factor and attempts have been made to identify the causative
element. Reduction in lead emitted from the combustion of leaded gasoline is a prime candi-
date, but as yet no causal relationship has been definitively established.
Blood lead data from the NHANES II study demonstrates well, on a nationwide basis, a sig-
nificant downward trend over time (Annest et al., 1982). Mean blood lead levels dropped from
15.8 |jg/dl during the first six months of the survey to 10.0 pg/dl during the last six months.
Mean values from these national data presented in six months increments from February 1976 to
February 1980 are displayed in Figure 1-14.
Billick and colleagues have analyzed the results of blood lead screening programs con-
ducted by the City of New York. Geometric mean blood lead levels decreased for all three
racial groups and for almost all age groups in the period 1970-76. Figure 1-15 shows that the
downward trend covers the entire range of the frequency distribution of blood lead levels.
The decline in blood lead levels showed seasonal variability, but the decrease in time was
consistent for each season.
Cause et al. (1977) present data from Newark, New Jersey, which reinforces the findings
of Billick and coworkers. Gause et al. studied the levels of blood lead among 5- and 6-year-
old children tested by the Newark Board of Education during the academic years 1973-74, 1974-
75, and 1975-76. Blood lead levels declined markedly during this 3-year period.
Rabinowitz and Needleman (1982) report a more recent study of umbilical cord blood lead
levels from 11,837 births between April, 1979 and April, 1981 in the Boston area. The overall
mean blood lead concentration was 6.56 ± 3.19 (standard deviation) with a range from 0.0 to
37.9 ug/dl. A downward trend in umbilical cord blood lead levels was noted over the two years
of the study.
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TABLE 1-9. WEIGHTED GEOMETRIC MEAN BLOOD LEAD LEVELS
FROM NHANES II SURVEY BY DEGREE OF URBANIZATION OF PLACE OF
RESIDENCE IN THE U.S. BY AGE AND RACE, UNITED STATES 1976-80
Race and age
All races
All ages
6 months-5 years
6-17 years
18-74 years
Whites
All ages
Degree of
Urban,
Ł1 million
Geometric
14.0
16.8
13.1
14.1
14.0
urbanization
Urban ,
<1 million
mean (ug/dl)
12.8
15.3
11.7
12.9
12.5
Rural
11.9
13.1
10.7
12.2
11.7
6 months-5 years
6-17 years
18-74 years
15.6
12.7
14.3
Source: Annest et. al., 1982.
14.4
11.4
12.7
12.7
10.5
12.1
Blacks
All ages
6 months-5 years
6-17 years
18-74 years
14.4
20.9
14.6
13.9
14.7
19.3
13.6
14.7
14.4
16.4
12.9
14.9
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o
x
-o
25
3.
_f
111
tu
Q 15
o
o
o
I
UJ
10
"WINTER 1976
(FEB.)
WINTER 1977
(FEB.)
WINTER 1978
(FEB.)
WINTER 1979
(FEB.)
WINTER 1380
(FEB.)
I
I
-o
30
-<
a
ya
10 15 20 25 30 35
CHRONOLOGICAL ORDER, 1 unit = 28 days
40
45
50
55
Figure 1-14. Average blood lead levels of U.S. population 6 months—74 years-. United States,
February 1976—February 1980, based on dates of examination of NHANES II examinees with
blood lead determinations.
Source: Annest et al. (1983).
u>
CO
w
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50
I I I I I I I I I I
CHICAGO
NEW YORK
1970 1971 1972 1973 1974 1976 1976 1977 1978 1979 1980
YEAR (Beginning Jan. 1)
Figure 1-15. Time dependence of blood lead for blacks, aged 24 to 35
months, in New York City and Chicago.
Source: Adapted from Billick (1982).
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The importance of the distributional form of blood lead levels is that the distributional
form determines which measure of central tendency (arithmetic mean, geometric mean, median) Is
most appropriate. It is even more important in estimating percent!les in the tail of the dis-
tribution, which represents those individuals at highest risk exposure-wise.
Based on the examination of the NHANES II data, as well as the results of several other
papers, it appears that the lognormal distribution is the most appropriate for describing the
distribution of blood lead levels in homogeneous populations with nearly constant external
exposure levels. The lognormal distribution appears to fit well across the entire range of the
distribution, including the right tail of the distribution. Blood lead levels, examined on a
population basis, have similarly skewed distributions. Blood lead levels from a population
thought to be homogenous in terms of demographic and lead exposure characteristics approxi-
mately follow a lognormal distribution. The geometric standard deviation for four different
studies are shown in Table 1-10. The values, including analytic error, are about 1.4 f0r
children and possibly somewhat smaller for adults. This allows an estimation of the upper
tail of the blood lead distribution, the group at higher risk.
Results obtained from the NHANES II study show that urban children generally have the
highest blood lead levels of any non-occupationally exposed population group. Furthermore,
black urban children have significantly higher blood lead levels than white urban children.
Several case control studies of children have shown that blood lead levels are related to hand
lead levels, house dust levels, lead in outside soil, interior paint lead level, and history
of pica. These factors are discussed in greater detail in the following sections.
1.11.2 Blood Lead vs. Inhaled Air Lead Relationships
The mass of data on the relationship of blood lead level and air lead exposure is compli-
cated by the need for reconciling the results of experimental and observational studies.
Further, the process of determining the best form of the statistical relationship deduced is
problematic due to the lack of consistency of range of the air lead expsoures encountered in
the various studies.
Because the main purpose of this document is to examine relationships of lead in air and
lead in blood under ambient conditions, EPA has chosen to emphasize the results of studies
most appropriately addressing this issue. A summary of the most appropriate studies appears
in Table 1-11. At air lead exposures of 3 ug/ma or less, there is no statistically signifi-
cant difference between curvilinear and linear blood lead inhalation relationships. At air
lead exposures of 10 M9/m3 or more either nonlinear or linear relationships can be fitted.
Thus a reasonably consistent picture emerges in which the blood lead-air lead relationship by
direct inhalation was approximately linear in the range of normal ambient exposures (0,1 -
2.0 ug/m3.) Therefore EPA has fitted linear relationships to blood lead levels in the studies
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TABLE 1-10. SUMMARY OF POOLED GEOMETRIC STANDARD
DEVIATIONS AND ESTIMATED ANALYTIC ERRORS
Study
NHANES II
N.Y. Childhood
Pooled Geometric
Inner City
Black Children
1.37
1.41
Standard Deviations
Inner City
White Children
1.39
1.42
Adult
Females
1.36a
Adult
Males
1.40a
Estimated
Analytic
Error
0.021
(b)
1^ • I* » 1 • • •
Screening Study
Tepper-Levin
Azar et al.
1.30
1.29
0.056
0.042C
Note: To calculate an estimated person-to-person GSD, compute Exp [(In(GSD))2 -
Analytic Error)*].
apooled across areas of differing urbanization.
''not known, assumed to be similar to NHANES II.
ctaken from Lucas (1981).
to be described with the explicit understanding that the fitted relationships are intended
only to describe changes in blood due to modest changes in air lead among individuals whose
blood lead levels do not exceed 30 ug/dl.
The blood-lead inhalation slope estimates vary appreciably from one subject to another in
experimental and clinical studies, and from one study to another. The weighted slope and stan-
dard error estimates from the Griffin study (1.75 ± 0.35) were combined with those calculated
similarly for the Rabinowitz study in (2.14 ± 0.47) and the Kehoe study in Table 11-20 (1.25 ±
0.35 setting DH = 0), yielding a pooled weighted slope estimate of 1.64 ± 0.22 ug/dl per ug/m3
There are some advantages in using these experimental studies on adult males, but certain
deficiencies are acknowledged. The Kehoe study exposed subjects to a wide range of exposure
levels while in the exposure chamber, but did not control air lead exposures outside the
chamber. The Griffin study provided reasonable control of air lead exposure during the exper-
iment, but difficulties in defining the non-inhalation baseline for blood lead (especially in
the important experiment dt 3 ug/m3) add much uncertainty to the estimate. The Rabinowitz
study controlled well for diet and other factors and, since they used stable lead isotope
tracers, they had no baseline problem. However, the actual air lead exposure of these
subjects outside the metabolic ward was not well determined.
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TABLE 1-11. SUMMARY OF BLOOD INHALATION SLOPES
ug/dl per pg/m3
Population
Children
Adult
Male
Study
Angle and Mclntire
(1979) Omaha, NE
Roels et al. (1980)
Belgium
Yankel et al. (1977);
Walter et al. (1980)
Idaho
Azar et al. (1975).
Five groups
Griffin et al.
(1975) NY
prisoners
Gross
(1979)
Rabinowitz et al.
(1973, 1976, 1977)
Study
Type
Population
Population
Population
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 Sensitivity*
of Slope
(1.40-4.40)1'2'3
(1.55-2.46)1'2
(1.07-1.52)1'2'3
(1.08-1.59)2'3
(1.52-3.38)4
(1.25-1.55)2
(2.14-3.51)5
*Selected from among the mgst plausible statistically equivalent models. For nonlinear
models, slope at 1.0 ug/m .
Sensitive to choice of other correlated predictors such as dust and soil lead.
Sensitive to linear vs. nonlinear at low air lead.
Sensitive to age as a covariate.
Sensitive to baseline changes in controls.
Sensitive to assumed air lead exposure.
Among population studies, only the Azar study provides a slope estimate in which indivi-
dual air lead exposures are known. However, there was no control of dietary lead intake or
other factors that affect blood lead levels, and slope estimates assuming only air lead and
location as covariables (1.32 ± 0.38) are not significantly different from the pooled experi-
mental studies.
There are no experimental inhalation studies on adult females or on children. The inha-
lation slope for women should be roughly the same as that for men, assuming proportionally
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smaller air intake and blood volume. The assumption of proportional size is less plausible
for children. Slope estimates for children from population studies are used in which some
other important covariates of lead absorption were controlled or measured, e.g., age, sex,
dust exposure in the environment or on the hands. Inhalation slopes were estimated for the
studies of Angle and Mclntire (1.92 ± 0.60), Roels (2.46 ± 0.58), and Yankel et al. (1.53 ±
0.064). The standard error of the Yankel study is extremely low and a weighted pooled slope
estimate for children would reflect essentially that study alone. In this case the small
standard error estimate is attributable to the very large range of air lead exposures of chil-
dren in the Silver Valley (up to 22 ug/m ). The relationship is in fact not linear, but in-
creases more rapidly in the upper range of air lead exposures. The slope estimate at lower
air lead concentrations may not wholly reflect uncertainty about the shape of the curve at
higher concentrations. The unweighted mean slope of the three studies and its standard error
estimate are 1.97 ± 0.39.
To summarize the situation briefly: (1) The experimental studies at lower air lead
levels (3.2 ug/m or less) and lower blood levels (typically 30 ug/dl or less) have linear
blood lead inhalation relationships with slopes p. of 0-3.6 for most subjects. A typical
value of 1.64 ± 0.22 may be assumed for adults. (2) Population cross-sectional studies at
lower air lead and blood lead levels are approximately linear with slopes p of 0.8-2.0. (3)
Cross-sectional studies in occupational exposure situations in which air lead levels are
higher (much above 10 ug/m ) and blood lead levels are higher (above 40 ug/dl) show a much
more shallow linear blood lead inhalation relation. The slope p is in the range of 0.03-0.2.
(4) Cross-sectional and experimental studies at levels of air lead somewhat above the higher
ambient exposures (9-36 ug/m ) and blood leads of 30-40 ug/dl can be described either by
a nonlinear relationship with decreasing slope or by a linear relationship with intermediate
slope, approximately p = 0.5. Several biological mechanisms for these differences have been
discussed (Hammond et al., 1981; 0'Flaherty et al., 1982; Chamberlain, 1983; Chamberlain and
Heard, 1981). Since no explanation for the decrease in steepness of the blood lead inhalation
response to higher air lead levels has been generally accepted at this time, there is little
basis on which to select an interpolation formula from low air lead to high air lead expo-
sures. The increased steepness of the inhalation curve for the Kellogg/Silver Valley study is
inconsistent with the other studies presented. It may be that smelter situations are unique
and must be analyzed differently, or it may be that the curvatuve is the result of imprecise
exposure estimates. (5) The blood-lead inhalation slope for children is at least as steep as
that for adults, with an estimate of 1.97 ± 0.39 from three major studies. These slope esti-
mates are based on the assumption that an equilibrium level of blood lead is achieved within a
few months after exposure begins. This is only approximately true, since lead stored in the
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skeleton may return to blood after some years. Chamberlain et al. (1978) suggest that long
term inhalation slopes should be about 30 percent larger than these estimates. Inhalation
slopes quoted here are associated with a half-life of blood lead in adults of about 30 days
O'Flaherty et al. (1982) suggest that the blood-lead half-life may increase slightly with
duration of exposure, but this has not been confirmed (Kang et al., 1983).
Other studies, reviews, and analyses of the study are discussed in Section 11.4, to which
the reader is referred for a detailed discussion and for a review of the key studies and their
analyses.
It must not be assumed that the direct inhalation of air lead is the only air lead con-
tribution that needs to be considered. Smelter studies allow partial assessment of the air
lead contributions to soil, dust, and finger lead. Useful ecological models to study the pos-
sible propagation of lead through the food chain have not yet been developed. The direct in-
halation relationship does provide useful information on changes in blood lead as responses to
changes in air lead on a time scale of several months. The indirect pathways through dust and
soil and through the food chain may thus delay the total blood lead response to changes in air
lead, perhaps by one or more years.
1.11.3 Dietary Lead Exposures Including Water
Dietary absorption of lead varies greatly from one person to another and depends on the
physical and chemical form of the carrier, on nutritional status, and on whether lead is In-
gested with food or between meals. These distinctions are particularly important for con-
sumption of leaded paint, dust, and soil by children. Typical values of 10 percent absorption
of ingested lead into blood have been assumed for adults and 25-50 percent for children.
It is difficult to obtain accurate dose-response relationships between blood lead levels
and lead level in food or water. Dietary intake must be estimated by duplicate diets or fecal
lead determinations. Water lead levels can be determined with some accuracy, but the varyino
amounts of water consumed by different individuals adds to the uncertainty of the estimated
relationships.
Quantitative analyses relating blood lead levels and dietary lead exposures have been re-
ported. Studies on infants provide estimates that are in close agreement. Only one indivi-
dual study is available for adults; another estimate from a number of pooled studies is also
available. These two estimates are in good agreement. Most of the subjects in the Sherlock
et al. (1982) and United Kingdom Central Directorate on Environmental Pollution (1982) studies
received quite high dietary lead levels (>300 (jg/day). The fitted cube root equations give
high slopes at lower dietary lead levels. On the other hand, the linear slope of the United
Kingdom Central Directorate on Environmental Pollution (1982) study is probably an underesti-
mate of the slope at lower dietary lead levels. For these reasons, the Ryu et al. (1983)
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study is the most believable, although it only applies to infants. Estimates for adults
should be taken from the experimental studies or calculated from assumed absorption and half-
life values.
Most of the dietary intake supplements were so high that many of the subjects had blood
lead concentrations much in excess of 30 ug for a considerable part of the experiment. Blood
lead levels thus may not completely reflect lead exposure, due to the previously noted non-
linearity of blood lead response at high exposures. The slope estimates for adult dietary in-
take are about 0.02 ug/dl increase in blood lead per ug/d intake, but consideration of blood
lead kinetics may increase this value to about 0.04 ug/dl per ug/d intake. Such values are
somewhat (about 0.05 ug/dl per ud/d) lower than those estimated from the population studies
extrapolated to typical dietary intakes. The value for infants is much larger. The relation-
ship between blood lead and water lead is not clearly defined and is often described as non-
linear. Water lead intake varies greatly from one person to another. It has been assumed
that children can absorb 25 to 50 percent of lead in water. Many authors chose to fit cube
root models to their data, although polynomial and logarithmic models were also used. Unfor-
tunately, the form of the model greatly influences the estimated contributions to blood lead
levels from relatively low water lead concentrations.
Although there is close agreement in quantitative analyses of relationships between blood
lead levels and dietary lead concentrations, there is a larger degree of variability in
results of the various water lead studies. The relationship is curvilinear but its exact form
•js yet to be determined. At typical levels for U.S. populations the relationship appears to
be linear. The only study that determines the relationship based on lower water lead values
(<100 ug/1) is the Pocock et al. (1983) study. The data from this study, as well as the
authors themselves, suggest that the relationship is linear for this lower range of water lead
levels. Furthermore, the estimated contributions to blood lead levels from this study are
quite consistent with the polynomial models from other studies. For these reasons, the Pocock
et al. (1983) slope of 0.06 is considered to represent the best estimate. The possibility
still exists, however, that the higher estimates of the other studies may be correct in cer-
tain situations, especially at higher water lead levels (>100 ug/1).
1.11.4 Studies Relating Lead in Soil and Dust to Blood Lead
The relationship of exposure to lead contained in soil and house dust and the amount of
lead absorbed by humans, particularly children, has been the subject of a number of scientific
investigations. Some of these studies have been concerned with the effects of exposures
resulting from the ingestion of lead in dust (Duggan and Williams, 1977; Barltrop, 1975;
Creason et al., 1975); others have concentrated on the means by which the lead in soil and
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dust becomes available to the body (Sayre et al., 1974). Sayre et al. (1974) demonstrated the
feasibility of house dust as a source of lead for children in Rochester, NY. Two groups of
houses, one inner city and the other suburban, were chosen for the study. Lead-free sanitary
paper towels were used to collect dust samples from house surfaces and the hands of children
(Vostal et al., 1974). The medians for the hand and household samples were used as the cut-
points in the chi-square contingency analysis. A statistically significant difference between
the urban and suburban homes for dust levels was noted, as was a relationship between house-
hold dust levels and hand dust levels (Lepow et al., 1975).
Studies relating soil lead to blood lead levels are difficult to compare. The relation-
ship obviously depends on depth of soil lead, age of the children, sampling method, cleanli-
ness of the home, mouthing activities of the children, and possibly many other factors. Vari-
ous soil sampling methods and sampling depths have been used over time; as such they may not
be directly comparable and may produce a dilution effect of the major lead concentration con-
tribution from dust, which is located primarily in the top 2 cm of the soil.
Increases in soil dust lead significantly increase blood lead in children. From several
studies EPA estimates an increase of 0.6 to 6.8 ug/dl in blood lead for each increase of 1000
ug/g in soil lead concentration. The values from the Stark et al. (1982) study may represent
a reasonable median estimate, i.e. about 2.0 pg/dl for each 1000 pg/dl increase in soil lead.
Household dust also increases blood lead, children from the cleanest homes in the Kellogg/
Silver Valley Study having 6 ug/dl less lead in blood, on average, than those from the house-
holds with the most dust.
1.11.5 Paint Lead Exposures
A major source of environmental lead exposure for many members of the general population
comes from lead contained in both interior and exterior paint on dwellings. The amount of
lead present, as well as its accessibility, depends upon the age of the residence (because
older buildings contain paint manufactured before lead content was regulated) and the physical
condition of the paint. In a survey of lead levels in 2370 randomly selected dwellings in
Pittsburgh, PA (Shier and Hall, 1977), paint with high levels of lead were most frequently
found in pre-1940 residences. One cannot assume, however, that high level lead paint is
absent in dwellings built after 1940. In the case of the houses surveyed in Pittsburgh, about
20 percent of the residences built after 1960 have at least one surface with more than 1 5
mg/cm lead. In fiscal year 1981, the U.S. Centers for Disease Control (1982), screened
535,730 children and found 21,897 with lead toxicity. Of these cases, 15,472 dwellings were
inspected and 10,666 (approximately 67 percent) were found to have leaded paint.
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1.H.6 Specific Source Studies
Two field investigations have attempted to derive an estimate of the amount of lead from
gasoline that is absorbed by the blood of individuals. Both of these investigations used the
fact that the isotopes of lead are stable and thus, the varying proportions of the isotopes
present in blood and environmental samples can indicate the source of the lead. The Isotope
Lead Experiment (ILE) is a massive study that attempted to utilize differing proportions of
the isotopes in geologic formations to infer the proportion of lead in gasoline that is
absorbed by the body. The other study utilized existing natural shifts in isotopic pro-
portions in an attempt to do the same thing.
The ILE is a large scale community trial in which the geologic source of lead for
antiknock compounds in gasoline was manipulated to change the isotopic composition of lead in
the atmosphere (Garibaldi et al., 1975; Facchetti, 1979). The isotopic lead ratios obtained
in the samples analyzed are displayed in Figure 1-16. It can be easily seen that the airborne
particulate lead rapidly changed its isotope ratio in line with expectation. Ratios in the
blood samples appeared to lag somewhat behind. Background lead isotopic ratios were 1.1603 ±
0.0028 in rural areas and 1.1609 ± 0.0015 in Turin in 1975. In Turin school children in
1977-78, a mean isotopic ratio of 1.1347 was obtained.
Preliminary analysis of the isotope ratios in air lead has allowed the estimation of the
fractional contribution of gasoline in the city of Turin, in small communities within 25 km of
Turin and in small communities beyond 25 km (Facchetti and Geiss, 1982). At the time of maxi-
mal use of Australian lead isotope in gasoline (1978-79), about 87.3 percent of the air lead
in Turin and 58.7 percent of the air lead in the countryside was attributable to gasoline. The
determination of lead isotope ratios was essentially independent of specific air lead concen-
trations. During that time, air lead averaged about 2.0 pg/m3 in Turin (from 0.88 to 4.54
^ O
pg/m depending on location of the sampling site), about 0.56 ug/m in the nearby communities
(0.30 to 0.67 ug/m ), and about 0.30 |jg/m3 in distant locations.
Isotope ratios in the blood of 35 subjects also changed, and the fraction of lead in
blood attributable to gasoline could be estimated independently of blood level concentration.
The mean fraction decreased from 23.7 ± 5.4 percent in Turin to 12.5 ± 7.1 percent in the
nearby countryside, and to 11.0 ± 5.8 percent in the remote countryside.
These results can be combined with the actual blood lead concentrations to estimate the
fraction of the gasoline uptake that is attributable to direct inhalation and that which is
not. The results are shown in Table 1-12 (based on a suggestion by Dr. Fachetti). As con-
cluded earlier, an assumed value of p=1.6 is plausible for predicting the amount of lead ab-
sorbed into blood at air lead concentrations less than 2.0 pg/m . The predicted values for
airborne lead derived from leaded gasoline range from 0.28 to 2.79 (jg/dl in blood due to
direct inhalation. The total contribution of blood lead from gasoline is much larger, from
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I I I I I I I I I I I I I I I I
*) BASED ON A LIMITED NUMBER OF SAMPLES
Pb 206/Pb 207
• ADULTS < 25 km
BLOOD A ADULTS > 25 km
O ADULTS TURIN
D TRAFFIC WARDENS-TURIN
• SCHOOL CHILDREN-TURIN
1.20
1.18
1.16
1.14
1.12
1.10
1.08
1.06
AIRBORNE
PARTICULATE
• TURIN
A COUNTRYSIDE
O PETROL
Phase 0
Phase 1
Phase 2
Phase 3
I I I I I I I I I I I I I I I I I
74
75 76
77
78
79
80
81
Figure 1-16. Change in Pb-206/Pb 207 ratios in petrol, airborne participate,
and blood from 1974 to 1981.
Source: Facchetti and Geiss (1982).
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TABLE 1-12. ESTIMATED CONTRIBUTION OF LEADED GASOLINE TO BLOOD LEAD
BY INHALATION AND NON-INHALATION PATHWAYS
Location
— ~
Turin
<25 km
>25 km
Air Lead
Fraction
From
Gaso-
line3
0.873
0.587
0.587
Air
Lead .
Cone.
(ug/m3)
2.0
0.56
0.30
Lead
Fraction
From
Gaso-
line0
0.237
0.125
0.110
Mean
Blood
Lead .
Cone.
(ug/dl)
21.77
25.06
31.78
Blood
Lead
From
Gaso-
line6
(ug/di)
5.16
3.13
3.50
Lead
From
Gasol i oe
In Air
(ug/di)
2.79
0.53
0.28
Non-
Inhaled
Lead From
Gaso-
line9
(ug/dl)
2.37
2.60
3.22
Estimated
Fraction
Gas- Lead h
Inhalation
0.54
0.17
0.08
aFraction of air lead in Phase 2 attributable to lead in gasoline.
bMean air lead in Phase 2, ug/m .
cMean fraction of blood lead in Phase 2 attributable to lead in gasoline.
^Mean blood lead concentration in Phase 2, ug/dl.
eŁstimated blood lead from gasoline = (c) x (d)
fEstimated blood lead from gas inhalation = B x (a) x (b), 8 = 1.6.
^Estimated blood lead from gas, non-inhalation = (f)-(e)
fraction of blood lead uptake from gasoline attributable to direct inhalation = (f)/(e)
Data from Facchetti and Geiss (1982), pp. 52-56.
3.50 to 5.16 pg/dl, suggesting that the non-inhalation total contribution of gasoline in-
creases from 2.37 ug/dl in Turin to 2.60 ug/dl in the near region and 3.22 ug/dl in the more
distant region. The non-inhalation sources include ingestion of dust and soil lead and lead
in food and drinking water. Efforts are being made to quantify their magnitude. The average
direct inhalation of lead in the air from gasoline is 8-17 percent of the total intake attri-
butable to gasoline in the countryside and an estimated 68 percent in the city of Turin.
Manton (1977) conducted a long term study of 10 subjects whose blood lead isotopic com-
position was monitored for comparison with the isotopic composition of the air they breathed.
Manton had observed that the ratio of lead 206/204 in the air varied with seasons in Dallas,
Texas; therefore, the ratio of those isotopes should vary in the blood. By comparing the
observed variability, estimates could then be made of the amount of lead in air that is
absorbed by the blood. From the Manton study it is estimated that between 7 and 41 percent of
the blood lead in study subjects in Dallas results from airborne lead. Additionally these
data provide a means of estimating the indirect contribution of air lead to blood lead. By
one estimate, only 10-20 percent of the total airborne contributions in Dallas is from direct
inhalation.
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In summary, the direct inhalation pathway accounts for only a fraction of the total air
lead concentration of blood, the direct inhalation contribution being on the order of 12-23
percent of the total uptake of lead attributable to gasoline, using Stephen's assumptions.
This is consistent with estimates from the ILE study.
Another approach was taken in New York City. Billick et al. (1979) presented several
possible explanations for observed declines in blood lead levels (discussed earlier above) and
evidence supporting and refuting each. The suggested contributing factors were the active
educational and screening program of the New York City Bureau of Lead Poisoning Control, and
the decrease in the amount of lead-based paint exposure as a result of rehabilitation or
removal of older housing stock of changes in environmental lead exposure. Information was
available only to partially evaluate the last source of lead exposure and particularly only
for ambient air lead levels. Air lead measurements were available during the entire study
period for only one station which was located on the west side of Manhattan at a height of
56 m. Superimposition of the air lead and blood lead levels indicated a similarity in both
upward cycle and decline. The authors cautioned against overinterpretation by assuming that
one air monitoring site was representative of the air lead exposure of New York City resi-
dents. With this in mind, the investigators fitted a multiple regression model to the data to
try to define the important determinants of blood lead levels for this population. Age, eth-
nic group and air lead level were all found to be significant determinants of blood lead
levels. The authors further point out the possibility of a change in the nature of the popu-
lation being screened before and after 1973. They reran this regression analysis separately
for years both before and after 1973. The same results were still obtained, although the
exact coefficients derived varied.
Billick et al. (1980) extended their previous analysis of the data from the single moni-
toring site mentioned earlier. The investigators examined the possible relationship between
blood lead level and the amount of lead in gasoline used in the New York City area. Figures
1-17 and 1-18 present illustrative trend lines in blood leads for blacks and Hispanics and air
lead and gasoline lead, respectively. Several different measures of gasoline lead were used:
(1) mid-Atlantic Coast (NY, NJ, Conn); (2) New York City plus New Jersey, and (3) New York
city plus Connecticut. The lead in gasoline trend line appears to fit the blood lead trend
line better than the air lead trend, especially in the summer of 1973.
1.11.7 Primary Smelters Populations
In 1972, the Centers for Disease Control studied the relationships between blood lead
levels and environmental factors in the vicinity of a primary smelter emitting lead, copper
and zinc located in El Paso, Texas, that had been in operation since the late 1800's
(Landrigan et al., 1975; U.S. Centers for Disease Control, 1973). Daily high volume samples
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- 35
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nI I I I I I I I I I I I I I I I I I I I I I I I I I I I Inn
1970 1971 1972 1973 1974 1975 1976
QUARTERLY SAMPLING DATE
Figure 1-17. Geometric mean blood lead levels of New York City
children (aged 25-36 months) by ethnic group, and ambient air lead
concentration versus quarterly sampling period, 1970-1976.
Source: Billick et al. (1980).
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E
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1970 1971 1972 1973 1974 1975 1976
QUARTERLY SAMPLING DATE
Figure 1-18. Geometric mean blood lead levels of New York City
children (aged 25-36 months) by ethnic group, and estimated
amount of lead present in gasoline sold in New York, New Jersey,
and Connecticut versus quarterly sampling period, 1970-1976.
Source: Billick et al. (1980).
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O
collected on 86 days between February and June, 1972 averaged 6.6 ug/m . These air lead
levels fell off rapidly with distance, reaching background values approximately 5 km from the
smelter. Levels were higher downwind, however. High concentrations of lead in soil and house
dusts were found, with the highest levels occurring near the smelter. The geometric means of
lead content in 82 soil and 106 dust samples from the sector closest to the smelter were 1791
and 4022 ug/g, respectively. Geometric means of both soil and dust lead levels near the
smelter were significantly higher than those in study sectors 2 or 3 km farther away. Sixty-
nine percent of children 1- to 4-years old living near the smelter had blood lead levels <40
ug/dl, and 14 percent had blood lead levels that exceeded 60 ug/dl. Concentrations in older
individuals were lower; nevertheless, 45 percent of the children 5- to 9-years old, 31 percent
of the individuals 10- to 19-years old, and 16 percent of the individuals above age 19 had
blood lead levels exceeding 40 ug/dl.
Cavalleri et al. (1981) studied children in the vicinity of a lead smelter and children
from a control area (4 km from the smelter). Since the smelter had installed filters 8 years
before the study, the older children living in the smelter area had a much higher lifetime
exposure. A striking difference in blood lead levels of the exposed and control populations
was observed; levels in the exposed population were almost twice that in the control popula-
tion. The geometric mean for nursery school children was 15.9 and 8.2 ug/dl for exposed and
control, respectively. For primary school it was 16.1 and 7.0 ug/dl. The air lead levels
were between 2 to 3 (jg/m in the exposed and 0.56 pg/m in the control cases.
1.11.8 Secondary Exposure of Children
Excessive intake and absorption of lead on the part of children can result when parents
who work in a dusty environment with a high lead content bring dust home on their clothing,
their shoes, or even their automobiles. Once home, their children are exposed to the high-
lead content dust.
Landrigan et al. (1976) reported that the 174, children of smelter workers who live within
24 km of a smelter had significantly higher blood lead levels (a mean of 55.1 ug/dl) than 511
children of persons in other occupations who lived in the same areas (whose mean blood lead
levels were 43.7 ug/dl). Other studies have documented increased lead absorption in children
Of families where at least one member was occupationally exposed to lead (Fischbein et al.,
1980a). The occupational exposures often involved battery plant operations (Morton et al.,
1982; U.S. Centers for Disease Control, 1977; Dolcourt et al., 1978, 1981; Watson et al.,
1978; Ferguson et al., 1981), as well as other occupations (Snee, 1982b; Rice et al., 1978).
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1.12 BIOLOGICAL EFFECTS OF LEAD EXPOSURE
1.12.1 Introduction
Lead has diverse biological effects in humans and animals. Its effects are seen at the
subcellular level of organellar structures and processes as well as at the overall level of
general functioning that encompasses all systems of the body operating in a coordinated, In-
terdependent fashion.
This review seeks not only to categorize and describe the various biological effects of
lead but to identify the exposure levels at which such effects occur and the mechanisms under-
lying them. The dose-response curve for the entire range of lead's biological effects is
rather broad, with certain biochemical changes occurring at relatively low levels of expo-
sure and perturbations in some organ systems, such as the endocrine, being obvious only at
relatively high exposure levels. In terms of relative vulnerability to lead's deleterious
effects, the developing organism appears to be more sensitive than the mature individual
particularly where the neurotoxic effects of lead are concerned.
1.12.2 Subcellular Effects of Lead
The biological basis of lead toxicity is its ability to bind to ligating groups in bio-
molecular substances crucial to various physiological functions, thereby interfering with
these functions by, for example, competing with native essential metals for binding sites
inhibiting enzyme activity, and inhibiting or otherwise altering essential ion transport.
These effects are modulated by: (1) the inherent stability of such binding sites for lead;
(2) the compartmentalization kinetics governing lead distribution among body compartments,
among tissues, and within cells; and (3) the differences in biochemical organization across
cells and tissues due to their specific functions. Given the complexities introduced by items
2 and 3, it is not surprising that no single, unifying mechanism of lead toxicity across all
tissues in humans and experimental animals has yet been identified.
In so far as effects of lead on activity of various enzymes are concerned, many of the
available studies concern j_n vitro behavior of relatively pure enzymes with marginal relevance
to various effects i_n vivo. On the other hand, certain enzymes are basic to the effects of
lead at the organ or organ system level, and discussion is best reserved for such effects in
sections below dealing with particular organ systems. This section is mainly concerned with
organellar effects of lead, particularly those which provide some rationale for lead toxicity
at higher levels of biological organization. Particular emphasis is placed on the mitochon-
drion, since this organelle is not only affected by lead in a number of ways but has provided
the most data.
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The main target organelle for lead toxicity in a variety of cell and tissue types clearly
is the mitochondrion, followed probably by cellular and intracellular membranes. The mito-
chondria! effects take the form of structural changes and marked disturbances in mitochondrial
function within the cell, particularly in energy metabolism and ion transport. These effects
in turn are associated with demonstrable accumulation of lead in mitochondria, both jji vivo
and in vitro. Structural changes include mitochondrial swelling in a variety of cell types as
well as distortion and loss of cristae, which may occur at relatively moderate levels of lead
exposure. Similar changes have also been documented in lead workers across a range of ex-
posure levels.
Uncoupled energy metabolism, inhibited cellular respiration using both succinate and
nicotinamide adenine dinucleotide (NAD)-linked substrates, and altered kinetics of intracellu-
lar calcium have been demonstrated jjn vivo using mitochondria of brain and non-neural tissue.
In some cases, the lead exposure level associated with such changes has been relatively moder-
ate. Studies documenting the relatively greater sensitivity of this organelle in young vs.
adult animals in terms of mitochondrial respiration have been reported. The cerebellum
appears to be particularly sensitive, providing a connection between mitochondrial impairment
and lead encephalopathy. Impairment by lead of mitochondrial function in the developing brain
has also been consistently associated with delayed brain development, as indexed by content of
various cytochromes. In the rat pup, ongoing lead exposure from birth is required for this
effect to be expressed, indicating that such exposure must occur before, and is inhibitory to,
the burst of oxidative metabolism activity that occurs in the young rat at 10 through 21 days
postnatally.
In vivo lead exposure of adult rats has also been seen to markedly inhibit cerebral cor-
tex intracellular calcium turnover in a cellular compartment that appears to be the mitochon-
drion. The effect was seen at a brain lead level of 0.4 ppm. These results are consistent
with a separate study showing increased retention of calcium in the brain of lead-dosed guinea
nigs- A number of reports have described the _u> vivo accumulation of lead in mitochondria of
kidney, liver, spleen, and brain tissue, with one study showing that such uptake was slightly
more than occurred in the nucleus. These data are not only consistent with the various dele-
terious effects of lead on mitochondria but are also supported by other investigations i_n
vitro-
Significant decreases in mitochondrial respiration |n vitro using both NAD-1inked and
succinate substrates have been observed for brain and non-neural tissue mitochondria in the
uresence of lead at micromolar levels. There appears to be substrate specificity in the inhi-
bition of respiration across different tissues, which may be a factor in differential organ
toxicity. Also, a number of enzymes involved in intermediary metabolism in isolated mitochon-
dria have been observed to undergo significant inhibition of activity with lead.
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A particular focus on lead's effects on isolated mitochondria has been ion transport
especially with regard to calcium. Lead movement into brain and other tissue mitochondria
involves active transport, as does calcium. Recent sophisticated kinetic analyses of desat-
uration curves for radiolabeled lead or calcium indicate that there is striking overlap in the
cellular metabolism of calcium and lead. These studies not only establish the basis of lead's
easy entry into cells and cell compartments, but also provide a basis for lead's impairment of
intracellular ion transport, particularly in neural cell mitochondria, where the capacity for
calcium transport is 20-fold higher than even in heart mitochondria.
Lead is also selectively taken up in isolated mitochondria j_n vitro, including the mito-
chondria of synaptosomes and brain capillaries. Given the diverse and extensive evidence of
lead's impairment of mitochondrial structure and function as viewed from a subcellular level
it is not surprising that these derangements are logically held to be the basis of dysfunction
of heme biosynthesis, erythropoiesis, and the central nervous system. Several key enzymes in
the heme biosynthetic pathway are intramitochondrial, particularly ferrochelatase. Hence it
is to be expected that entry of lead into mitochondria will impair overall heme biosynthesis
and in fact this appears to be the case in the developing cerebellum. Furthermore, the levels
of lead exposure associated with entry of lead into mitochondria and expression of mitochon-
drial injury can be relatively moderate.
Lead exposure provokes a typical cellular reaction in human and other species that has
been morphologically characterized as a lead-containing nuclear inclusion body. While it has
been postulated that such inclusions constitute a cellular protection mechanism, such a
mechanism is an imperfect one. Other organelles, e.g., the mitochondrion, also take up lead'
and sustain injury in the presence of inclusion formations. Chromosomal effects and other
indices of genotoxicity in humans and animals are considered in Section 1.12.7.
In theory, the cell membrane is the first organelle to encounter lead and it is not
surprising that cellular effects of lead can be ascribed to interactions at cellular and
intracellular membranes in the form of distrubed ion transport. The inhibition of membrane
(Na ,K )-ATPase of erythrocytes as a factor in lead-impaired erythropoiesis is noted else-
where. Lead also appears to interfere with the normal processes of calcium transport across
membranes of different tissues. In peripheral cholinergic synaptosomes, lead is associated
with retarded release of acetylcholine owing to a blockade of calcium binding to the membrane
while calcium accumulation within nerve endings can be ascribed to inhibition of membrane
(Na"'",K'l")-ATPase.
Lysosomes accumulate in renal proximal convoluted tubule cells of rats and rabbits given
lead over a range of dosing. This also appears to occur in the kidneys of lead workers and
seems to represent a disturbance in normal lysosomal function, with the accumulation of
lysosomes being due to enhanced degradation of proteins because of the effects of lead else-
where within the cell.
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1.12.3. Effects of Lead on Heme Biosynthesis, Erythropoiesis. and Erythrocyte Physiology in
Humans and Animals
The effects of lead on heme biosynthesis are well known because of both their prominence
and the large number of studies of these effects in humans and experimental animals. The
process of heme biosynthesis starts with glycine and succinyl-coenzyme A, proceeds through
formation of protoporphyrin IX, and culminates with the insertion of divalent iron into the
porphyrin ring, thus forming heme. In addition to being a constituent of hemoglobin, heme is
the prosthetic group of a number of tissue hemoproteins having variable functions, such as
myoglobin, the P-450 component of the mixed function oxygenase system, and the cytochromes of
cellular energetics. Hence, disturbance of heme biosynthesis by lead poses the potential for
multiple-organ toxicity.
At present, the steps in the heme synthesis pathway that have been best studied with re-
spect to lead's effects involve three enzymes: (1) stimulation of mitochondrial delta-amino-
levulinic acid synthetase (ALA-S), which mediates the formation of delta-aminolevulinic acid
(ALA); (2) direct inhibition of the cytosolic enzyme, delta-aminolevulinic acid dehydrase
(ALA-D), which catalyzes formation of porphobilinogen from two units of ALA; and (3) inhibi-
tion of the insertion of iron (II) into protoporphyrin IX to form heme, a process mediated by
the enzyme ferrochelatase.
Increased ALA-S activity has been documented in lead workers as well as lead-exposed ani-
mals, although the converse, an actual decrease in enzyme activity, has also been observed in
several experimental studies using different exposure methods. It would appear, then, that
enzyme activity increase via feedback derepression or that activity inhibition may depend on
the nature of the exposure. In an ui vitro study using rat liver cells in culture, ALA-S
activity could be stimulated at levels as low as 5.0 pM or 1.0 |jg Pb/g preparation. In the
same study, increased activity was seen to be due to biosynthesis of more enzyme. The thres-
hold for lead stimulation of ALA-S activity in humans, based upon a study using leukocytes
from lead workers, appears to be about 40 ug Pb/dl. The generality of this threshold level to
other tissues is dependent upon how well the sensitivity of leukocyte mitochondria mirrors
that in other systems. It would appear that the relative impact of ALA-S activity stimulation
on ALA accumulation at lower levels of lead exposure is considerably less than the effect of
ALA'D activity inhibition: at 40 ug/dl blood lead, ALA-D activity is significantly depressed,
whereas ALA-S activity only begins to be affected at that blood lead concentration.
Erythrocyte ALA-D activity is very sensitive to lead inhibition, which is reversed by re-
activation of the sulfhydryl group with agents such as dithiothreitol, zinc, or zinc plus glu-
tathione. The zinc levels employed to achieve reactivation, however, are well above normal
physiological levels. Although zinc appears to offset the inhibitory effects of lead observed
in human erythrocytes jn vitro and in animal studies, lead workers exposed to both zinc and
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lead do not show significant changes in the relationship of ALA-D activity to blood lead con-
centration when compared to workers exposed only to lead. In contrast, zinc deficiency in
animals has been shown to significantly inhibit ALA-D activity, with concomitant accumulation
of ALA in urine. Since zinc deficiency has also been associated with increased lead absorp-
tion in experimental studies, the possibility exists for a dual effect of such deficiency on
ALA-D activity: (1) a direct effect on activity due to reduced zinc availability, as well as
(2) the effect of increased lead absorption leading to further inhibition of such activity.
The activity of erythrocyte ALA-D appears to be inhibited at virtually all blood lead
levels measured so far, and any threshold for this effect in either adults or children remains
to be determined. A further measure of this enzyme's sensitivity to lead comes from a report
noting that rat bone marrow suspensions show inhibition of ALA-D activity by lead at a level
of 0.1 ug/g suspension. Inhibition of ALA-D activity in erythrocytes apparently reflects a
similar effect in other tissues. Hepatic ALA-D activity was inversely correlated in lead
workers with both the erythrocyte activity as well as blood lead. Of significance are the ex-
perimental animal data showing that (1) brain ALA-D activity is inhibited with lead exposure
and (2) inhibition appears to occur to a greater extent in the brain of developing vs. adult
animals. This presumably reflects greater retention of lead in developing animals. In the
avian brain, cerebellar ALA-D activity is affected to a greater extent than that of the
cerebrum and, relative to lead concentration, shows inhibition approaching that occurring in
erythrocytes.
The inhibition of ALA-D activity by lead is reflected in increased levels of its sub-
strate, ALA, in blood, urine, and tissues. In one investigation, the increase in urinary ALA
was seen to be preceded by a rise in circulating levels of the metabolite. Blood ALA levels
were elevated at all corresponding blood lead values down to the lowest value determined (18
ug/dl), while urinary ALA was seen to rise exponentially with blood ALA. Urinary ALA has been
employed extensively as an indicator of excessive lead exposure in lead workers. The value of
this measurement for diagnostic purposes in pediatric screening, however, is limited if only
spot urine collection is done; more satisfactory data can be obtained in cases where 24-hour
collections are feasible. A large number of independent studies have documented that there is
a direct correlation between blood lead and the logarithm of urinary ALA in adult humans and
children, and that the threshold is commonly accepted as being 40 ug/dl. Several studies of
.lead workers also indicate that the correlation of urinary ALA with blood lead continues below
this value. Furthermore, one report has demonstrated that the slope of the dose-effect curve
in lead workers is dependent upon the level of exposure.
The health significance of lead-inhibited ALA-D activity and accumulation of ALA at low
levels of exposure has been an issue of some controversy. One view is that the "reserve
capacity" of ALA-D activity is such that only high accumulations of the enzyme's substrate
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ALA, in accessible indicator media would result in significant inhibition of activity. One
difficulty with this view is that it is not possible to quantify at lower levels of lead ex-
posure the relationship of urinary ALA to levels in target tissues nor to relate the potential
neurotoxicity of ALA at any level of build-up to levels in indicator media; i.e., the thres-
hold for potential neurotoxicity of ALA in terms of blood lead may be different from the level
associated with urinary accumulation.
Accumulation of protoporphyrin in the erythrocytes of individuals with lead intoxication
has been recognized since the 1930s, but it has only recently been possible to quantitatively
assess the nature of this effect via the development of specific, sensitive micromethods of
analysis. Accumulation of protoporphyrin IX in erythrocytes is the result of impaired place-
ment of iron (II) in the porphyrin moiety to form heme, an intramitochondrial process mediated
by the enzyme ferrochelatase. In lead exposure, the porphyrin acquires a zinc ion in lieu of
native iron, thus forming zinc protoporphyrin (ZPP), and is tightly bound in available heme
pockets for the life of the erythrocytes. This tight sequestration contrasts with the rela-
tively mobile non-metal, or free, erythrocyte protoporphyrin (FEP) accumulated in the congen-
ital disorder erythropoietic protoporphyria.
Elevation of erythrocyte ZPP has been extensively documented as being exponentially cor-
related with blood lead in children and adult lead workers and is presently considered one of
the best indicators of undue lead exposure. Accumulation of ZPP only occurs in erythrocytes
formed during lead's presence in erythroid tissue, resulting in a lag of at least several
weeks before such build-up can be measured. It has been shown that the level of such accumu-
lation in erythrocytes of newly-employed lead workers continues to increase when blood V>^.
has already reached a plateau. This would influence the relative correlation of ZPP and blood
lead in workers with a short exposure history. In individuals removed from occupational expo-
sure, the ZPP level in blood declines much more slowly than blood lead, even years after re-
moval from exposure or after a drop in blood lead. Hence, ZPP level would appear to be a more
reliable indicator of continuing intoxication from lead resorbed from bone.
The measurable threshold for the effect of lead on ZPP accumulation is affected by the
relative spread of blood lead and corresponding ZPP values measured. In young children (under
four years of age) the ZPP elevation typically associated with iron-deficiency anemia should
be taken into account. In adults, a number of studies indicate that the threshold for ZPP
elevation with respect to blood lead is approximately 25-30 ug/dl. In children 10-15 years
old the threshold is about 16 ug/dl; in this age group, iron deficiency is not a factor. In
one report, it was noted that children over four years of age showed the same threshold, 15.5
ug/dl, as a second group under four years old, indicating that iron deficiency was not a
factor in the study. Fifty percent of the children were found to have significantly elevated
EP levels (2 standard deviations [SDs] above reference mean EP) or a dose-response threshold
level of 25 ug/dl.
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Below 30-40 (jg/dl, any assessment of the ZPP-blood lead relationship is strongly influ-
enced by the relative analytical proficiency for measurement of both blood lead and EP. The
types of statistical treatments given the data are also important. In a recent detailed sta-
tistical study involving 2004 children, 1852 of whom had blood lead values below 30 ug/dl,
segmental line and probit analysis techniques were employed to assess the dose-effect thres-
hold and dose-response relationship. An average blood lead threshold for the effect using
both statistical techniques yielded a value of 16.5 MQ/dl for either the full group or those
subjects with blood lead levels below 30 ug/dl. The effect of iron deficiency was tested for
and removed. Of particular interest was the finding that the blood lead values corresponding
to EP elevations more than 1 or 2 standard deviations above the reference mean in 50 percent
of the children were 28.6 or 35.7 ug Pb/dl, respectively. Hence, fully half of the children
were seen to have significant elevations of EP at blood lead levels around the currently used
cut-off value for undue lead exposure, 30 ug/dl. From various reports, children and adult
females appear to be more sensitive to the effects of lead on EP accumulation at any given
blood lead level, with children being somewhat more sensitive than adult females.
Effects of lead on ZPP accumulation and reduced heme formation are not restricted to the
erythropoietic system. Recent studies show that reduction of serum 1,25-dihydroxy vitamin D
seen with even low level lead exposure is apparently the result of lead's inhibition of the
activity of renal 1-hydroxylase, a cytochrome P-450 mediated enzyme. Cytochrome P-450 a
heme-containing protein, is an integral part of the hepatic mixed function oxygenase system
and is known to be affected in humans and animals by lead exposure, particularly acute
intoxication. Reduced P-450 content has been found to be correlated with impaired activity of
such detoxifying enzyme systems as aniline hydroxylase and aminopyrine demethylase.
Studies of organotypic chick dorsal root ganglion in culture show that the nervous system
not only has heme biosynthetic capability but that such preparations elaborate porphyrinic ma-
terial in the presence of lead. In the neonatal rat, chronic exposure to lead resulting in
moderately elevated blood lead levels is associated with retarded growth in the hemoprotein
cytochrome C and with disturbed electron transport in the developing rat cerebral cortex.
These data parallel the effect of lead on ALA-D activity and ALA accumulation in neural
tissue. When both of these effects are viewed within the toxicokinetic context of increased
retention of lead in both developing animals and children, there is an obvious, serious
potential for impaired heme-based metabolic function in the nervous system of lead-exposed
children.
As can be seen from the above discussion, the health significance of ZPP accumulation
rests with the fact that such build-up is evidence of impaired heme and hemoprotein formation
in tissues, particularly the nervous system, arising from entry of lead into mitbchondria.
Such evidence for reduced heme synthesis is consistent with a diverse body of data documenting
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lead-associated effects on mitochondria, including impairment of ferrochelatase activity. As
a mitochondria! enzyme, ferrochelatase activity may be inhibited either directly by lead or
indirectly by impairment of iron transport to the enzyme.
The relative value of the lead-ZPP relationship in erythropoietic tissue as an index of
this effect in other tissues hinges on the relative sensitivity of the erythropoietic system
compared with other systems. For example, one study of rats exposed to low levels of lead
over their lifetime demonstrated that protoporphyrin accumulation in renal tissue was already
significant at levels of lead exposure where little change was seen in erythrocyte porphyrin
levels. The issue of sensitivity is obviously distinct from the question of which system is
most accessible to measurement of the effect.
Other steps in the heme biosynthesis pathway are also known to be affected by lead, al-
though these have not been studied as much on a biochemical or molecular level. Levels of
coproporphyrin are increased in urine, reflecting active lead intoxication. Lead also affects
the activity of the enzyme uroporphyrinogen-I-synthetase, resulting in an accumulation of its
substrate, porphobilinogen. It has been reported that the erythrocyte enzyme is much more
sensitive to lead than the hepatic species and presumably accounts for much of the accumulated
substrate.
Anemia is a manifestation of chronic lead intoxication, being characterized as mildly
hypochromic and usually normocytic. It is associated with reticulocytosis, owing to shortened
cell survival, and the variable presence of basophilic stippling. Its occurrence is due to
both decreased production and increased rate of destruction of erythrocytes. In children
under four years of age, the anemia of iron deficiency is exacerbated by the effect of lead,
and vice versa. Hemoglobin production is negatively correlated with blood lead in young chil-
dren, where iron deficiency may be a confounding factor, as well as in lead workers. In one
study, blood lead values that were usually below 80 ug/dl were inversely correlated with hemo-
globin content. In these subjects, iron deficiency was found to be absent. The blood lead
threshold for reduced hemoglobin content is about 50 ug/dl in adult lead workers and somewhat
lower in children, around 40 ug/dl.
The mechanism of lead-associated anemia appears to be a combination of reduced hemoglobin
production and shortened erythrocyte survival because of direct cell injury. Effects of lead
on hemoglobin production involve disturbances of both heme and globin biosynthesis. The hemo-
lytic component to lead-induced anemia appears to be due to increased cell fragility and in-
creased osmotic resistance. In one study using rats, it was noted that the reduced cell
deformability and consequent hemolysis associated with vitamin E deficiency is exacerbated by
lead exposure. The molecular basis for increased cell destruction rests with inhibition of
(Na*. K+)-ATPase and pyrimidine-5'-nucleotidase. Inhibition of the former enzyme leads to
cell "shrinkage," and inhibition of the latter results in impaired pyrimidine nucleotide
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phosphorolysis and disturbance of the activity of the purine nucleotides necessary for
cellular energetics.
Tetraethyl lead and tetramethyl lead, components of leaded gasoline, undergo transforma-
tion ui vivo to the neurotoxic trialkyl metabolites as well as further conversion to inorganic
lead. Hence, one might anticipate that exposure to such agents may show effects commonly
associated with inorganic lead in terms of heme synthesis and erythropoiesis.
Various surveys and case reports make it clear that the habit of sniffing leaded gasoline
is associated with chronic lead intoxication in children from socially deprived backgrounds in
rural or remote areas. Notable in these subjects is evidence of impaired heme biosynthesis as
indexed by significantly reduced ALA-D activity. In a number of case reports of frank lead
toxicity from habitual sniffing of leaded gasoline, such effects as basophilic stippling in
erythrocytes and significantly reduced hemoglobin have also been noted.
Lead-associated disturbances of heme biosynthesis as a possible factor in the neuro-
logical effects of lead have been the object of considerable interest because of (1) the
recognized similarity between the classical signs of lead neurotoxicity and a number of the
neurological components of the congenital disorder known as acute intermittent porphyria as
well as (2) some of the unusual aspects of lead neurotoxicity. There are two possible points
of connection between lead's effects on both heme biosynthesis and the nervous system. Con-
cerning the similarity of lead neurotoxicity to acute intermittent porphyria, there is the
common feature of excessive systemic accumulation and excretion of ALA. Second, lead neuro-
toxicity reflects, to some degree, impaired synthesis of heme and hemoproteins involved in
crucial cellular functions. Available information indicates that ALA levels are elevated in
the brain of lead-exposed animals, arising via ui situ inhibition of brain ALA-D activity or
via transport to the brain after formation in other tissues. ALA is known to traverse the
blood-brain barrier. Hence, ALA is accessible to, or formed within, the brain during lead ex-
posure and may express its neurotoxic potential.
Based on various in vitro and iji vivo data obtained in the context of neurochemical
studies of lead neurotoxicity, it appears that ALA can readily play a role in GABAergic func-
tion, particularly inhibiting release of the neurotransmitter GABA from presynaptic receptors
where ALA appears to be very potent even at low levels. In an ir\ vitro study, agonist
behavior by ALA was demonstrated at levels as low as 1.0 uM ALA. This in vitro observation
supports results of a study using lead-exposed rats in which there was reported inhibition of
both resting and K -stimulated preloaded 3H-GABA. Further evidence for an effect of some
agent other than lead acting directly is the observation that jji vivo effects of lead on
neurotransmitter function cannot, be duplicated with jjn vitro preparations to which lead is
added. Human data on lead-induced associations between disturbed heme synthesis and neuro-
toxicity, while limited, also suggest that ALA may function as a neurotoxicant.
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The connection of impaired heme and hemoprotein synthesis in the brain of the neonatal
rat was noted earlier. In these studies there was reduced cytochrome C production and im-
paired operation of the cytochrome C respiratory chain. Hence, one might expect that such
impairment would be most prominent in areas of relatively greater cellularization, such as the
hippocampus. As noted in Chapter 10, these are also regions where selective lead accumulation
appears to occur.
1.12.4 Neurotoxic Effects of Lead
An assessment of the impact of lead on human and animal neurobehavioral function raises
a number of issues. Among the key points addressed here are: (1) the internal exposure
levels, as indexed by blood lead levels, at which various adverse neurobehavioral effects
occur; (2) the reversibility of such deleterious effects; and (3) the populations that appear
to be most susceptible to neural damage. In addition, the question arises as to the utility
of using animal studies to draw parallels to the human condition.
1.12.4.1 Internal Lead Levels at which Neurotoxic Effects Occur. Markedly elevated blood
lead levels are associated with the most serious neurotoxic effects of lead exposure
(including severe, irreversible brain damage as indexed by the occurrence of acute or chronic
encephalopathic symptoms, or both) in both humans and animals. For most human adults, such
damage typically does not occur until blood lead levels exceed 120 ug/dl. Evidence does
exist, however, for acute encephalopathy and death occurring in some human adults at blood
lead levels of 100-120 ug/dl. In children, the effective blood lead level for producing
encephalopathy or death is lower, starting at approximately 80-100 ug/dl. It should be
emphasized that, once encephalopathy occurs, death is not an improbable outcome, regardless of
the quality of medical treatment available at the time of acute crisis. In fact, certain
diagnostic or treatment procedures themselves may exacerbate matters and push the outcome
toward fatality if the nature and severity of the problem are not diagnosed or fully recog-
nized. It is also crucial to note the rapidity with which acute encephalopathic symptoms can
develop or death can occur in apparently asymptomatic individuals or in those apparently only
mildly affected by elevated lead body burdens. Rapid deterioration often occurs, with
convulsions or coma suddenly appearing with progression to death within 48 hours. This
strongly suggests that even in apparently asymptomatic individuals, rather severe neural
damage probably exists at high blood lead levels even though it is not yet overtly manifested
in obvious encephalopathic symptoms. This conclusion is further supported by numerous studies
showing that overtly lead intoxicated children with high blood lead levels, but not observed
to manifest acute encephalopathic symptoms, are permanently cognitively impaired, as are most
children who survive acute episodes of frank lead encephalopathy.
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Recent studies show that overt signs and symptoms of neurotoxicity (indicative of both
CNS and peripheral nerve dysfunction) are detectable in some human adults at blood lead levels
as low as 40-60 ug/dl, levels well below the 60 or 80 ug/dl criteria previously discussed as
being "safe" for adult lead exposures. In addition, certain electrophysiological studies of
peripheral nerve function in lead workers, indicate that slowing of nerve conduction veloc-
ities in some peripheral nerves are associated with blood lead levels as low as 30-50 ug/dl
(with no clear threshold for the effect being evident). These results are indicative of
neurological dysfunctions occurring at relatively low lead levels in non-overtly lead intoxi-
cated adults.
Other evidence tends to confirm that neural dysfunctions exist in apparently asymptomatic
children, at similar or even lower levels of blood lead. The body of studies on low-or
moderate-level lead effects on neurobehavioral functions in non-overtly lead intoxicated child-
ren, as evaluated in Chapter 12, presents an array of data pointing to that conclusion.
Several well-controlled studies have found effects that are clearly statistically significant,
whereas other have found nonsignificant but borderline effects. Some studies reporting gener-
ally nonsignificant findings at times contain data confirming some statistically significant
effects, which the authors attribute to various extraneous factors. It should also be noted
that, given the apparent nonspecific nature of some of the behavioral or neural effects proba-
ble at low levels of lead exposure, one would not expect to find striking differences in every
instance. The lowest observed blood lead levels associated with significant neurobehavioral
deficits indicative of CNS dysfunction, both in apparently asymptomatic children and in devel-
oping rats and monkeys generally appear to be in the range of 30-50 ug/dl. However, other
types of neurotoxic effects, e.g., altered EEG patterns, have been reported at lower levels,
supporting a continuous dose-response relationship between lead and neurotoxicity. Such ef-
fects, when combined with adverse social factors (such as low parental IQ, low socioeconomic
status, poor nutrition, and poor quality of the caregiving environment) can place children,
especially those below the age of three years, at significant risk. However, it must be
acknowledged that nutritional covariates, as well as demographic social factors, have been
poorly controlled in many of the human studies reviewed. Socioeconomic status also is a crude
measure of parenting and family structure that requires further assessment as a possible con-
tributor to observed results of neurobehavioral studies.
Timing, type, and duration of exposure are important factors in both animal and human
studies. It is often uncertain whether observed blood lead levels represent the levels that
were responsible for observed behavioral deficits or electrophysiological changes. Monitoring
of lead exposures in human subjects in all cases has been highly intermittent or nonexistent
during the period of life preceding neurobehavioral assessment. In most human studies, only
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one or two blood lead values are provided per subject. Tooth lead may be an important cumula-
tive exposure index, but its modest, highly variable correlation to blood lead or FEP and to
external exposure levels makes findings from various studies difficult to compare quantita-
tively. The complexity of the many important covariates and their interaction with dependent
variable measures of modest validity, e.g., IQ tests, may also account for some discrepancies
among the different studies.
1.12.4.2 Early Development and the Susceptibility to Neural Damage. On the question of early
childhood vulnerability, the neurobehavioral data are consistent with morphological and bio-
chemical studies of the susceptibility of the heme biosynthetic pathway to perturbation by
lead. Various lines of evidence suggest that the order of susceptibility to lead's effects
is: (1) young > adults and (2) female > male. Animal studies also have pointed to the peri-
natal period of ontogeny as a particularly critical time for a variety of reasons: (1) it is
a period of rapid development of the nervous system; (2) it is a period where good nutrition
is particularly critical; and (3) it is a period where the caregiver environment is vital to
normal development. However, the precise boundaries of a critical period are not yet clear
and may vary depending on the species and function or endpoint that is being assessed. Never-
theless, there is general agreement that human infants and toddlers below the age of three
years are at special risk because of iji utero exposure, increased opportunity for exposure
because of normal mouthing behavior, and increased rates of lead absorption due to various
factors, e.g., nutritional deficiences.
1.12.4.3 The Question of Irreversibility. Little research on humans is available on persis-
tence of effects. Some work suggests that mild forms of peripheral neuropathy in lead workers
may be reversible after termination of lead exposure, but little is known regarding the rever-
sibility of lead effects on central nervous system function in humans. A recent two-year
follow-up study of 28 children of battery factory workers found a continuing relationship
between blood lead levels and altered slow wave voltage of cortical slow wave potentials indic-
ative of persisting CNS effects of lead. Current population studies, however, will have to be
supplemented by prospective longitudinal studies of the effects of lead on development in
order to address the issue of reversibility or persistence of lead neurotoxic effects in
humans more satisfactorily.
Various animal studies provide evidence that alterations in neurobehavioral function may
be long-lived, with such alterations being evident long after blood lead levels have returned
to control levels. These persistent effects have been demonstrated in monkeys as well as rats
under a variety of learning performance test paradigms. Such results are also consistent with
morphological, electrophysiological, and biochemical studies on animals that suggest lasting
changes in synaptogenesis, dendritic development, myelin and fiber tract formation, ionic
mechanisms of neurotransmission, and energy metabolism.
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1.12.4.4 Utility of Animal Studies in Drawing Parallels to the Human Condition. Animal
models are used to shed light on questions where it is impractical or ethically unacceptable
to use human subjects. This is particularly true in the case of exposure to environmental
toxins such as lead. In the case of lead, it has been effective and convenient to expose
developing animals via their mothers' milk or by gastric gavage, at least until weaning. In
many studies, exposure was continued in the water or food for some time beyond weaning. This
approach simulates at least two features commonly found in human exposure: oral intake and
exposure during early development. The preweaning period in rats and mice is of particular
relevance to in terms of parallels with the first two years or so of human brain development.
However, important questions exist concerning the comparability of animal models to
humans. Given differences between humans, rats, and monkeys in heme chemistry, metabolism,
and other aspects of physiology and anatomy, it is difficult to state what constitutes an
equivalent internal exposure level (much less an equivalent external exposure level). For
example, is a blood lead level of 30 ug/dl in a suckling rat equivalent to 30 ug/dl in a
three-year-old child? Until an answer is available to this question, i.e., until the function
describing the relationship of exposure indices in different species is available, the utility
of animal models for deriving dose-response functions relevant to humans will be limited.
Questions also exist regarding the comparability of neurobehavioral effects in animals
with human behavior and cognitive function. One difficulty in comparing behavioral endpoints
such as locomotor activity is the lack of a consistent operational definition. In addition to
the lack of standardized methodologies, behavior is notoriously difficult to "equate" or com-
pare meaningfully across species because behavioral analogies do not demonstrate behavioral
pomologies. Thus, it is improper to assume, without knowing more about the responsible under-
lying neurological structures and processes, that a rat's performance on an operant condition-
ing schedule or a monkey's performance on a stimulus discrimination task corresponds to a
child's performance on a cognitive function test. Still deficits in performance on such tasks
are indicative of altered CNS function which is likely to parallel some type of altered human
CNS function as well.
In terms of morphological findings, there are reports of hippocampal lesions in both
lead-exposed rats and humans that are consistent with a number of behavioral findings suggest-
ing an impaired ability to respond appropriately to altered contingencies for rewards. That
is, subjects tend to persist in certain patterns of behavior even when changed conditions make
the behavior inappropriate. Other morphological findings in animals, such as demyelination
and glial cell decline, are comparable to human neuropathologic observations mainly at rela-
tively high exposure levels.
Another neurobehavioral endpoint of interest in comparing human and animal neurotoxicity
of lead is electrophysiological function. Alterations of electroencephalographic patterns and
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cortical slow wave voltage have been reported for lead-exposed children, and various electro-
physiological alterations both jn vivo (e.g., in rat visual evoked response) and jjn vitro
(e.g., in frog miniature endplate potentials) have also been noted in laboratory animals. At
this time, however, these lines of work have not converged sufficiently to allow for strong
conclusions regarding the electrophysiological aspects of lead neurotoxicity.
Biochemical approaches to the experimental study of leads effects on the nervous system
have generally been limited to laboratory animal subjects. Although their linkage to human
neurobehavioral function is at this point somewhat speculative, such studies do provide in-
sight to possible neurochemical intermediaries of lead neurotoxicity. No single neurotrans-
mitter system has been shown to be particularly sensitive to the effects of lead exposure;
rather, lead-induced alterations have been demonstrated in several different neurotransmitter
systems, including dopamine, norepinephrine, serotonin, and gamma-aminobutyric acid. In addi-
tion, lead has been shown to have subcellular effects in the central nervous system at the
level of mitochondrial function and protein synthesis.
Given the above-noted difficulties in formulating a comparative basis for internal expo-
sure levels among different species, the primary value of many animal studies, particularly i_n
vitro studies, may be in the information they can provide on basic mechanisms involved in lead
neurotoxicity. A number of HI vitro studies show that significant, potentially deleterious
effects on nervous system function occur at HI situ lead concentrations of 5 uM and possibly
lower, suggesting that no threshold may exist for certain neurochemical effects of lead on a
subcellular or molecular level. The relationship between blood lead levels and lead concen-
trations at such extra- or intracellular sites of action, however, remains to be determined.
Despite the problems in generalizing from animals to humans, both the animal and the human
studies show great internal consistency in that they support a continuous dose-response
functional relationship between lead and neurotoxic biochemical, morphological, electrophysio-
logical, and behavioral effects.
1.12.5 Effects of Lead on the Kidney
It has been known for more than a century that kidney disease can result from lead
poisoning. Identifying the contributing causes and mechanisms of lead-induced nephropathy has
been difficult, however, in part because of the complexities of human exposure to lead and
other nephrotoxic agents.
Nevertheless, it is possible to estimate at least roughly lead exposure ranges associated
with detectable renal dysfunction in both human adults and children. More specifically,
numerous studies of occupationally exposed workers have provided evidence for lead-induced
chronic nephropathy being associated with blood lead levels ranging from 40 to more than
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100 ug/dli and some are suggestive of renal effects possibly occurring even at levels as low
as 30 Mg/dl. Similarly, in children, the relatively sparse evidence available points to the
manifestation of renal dysfunction, as indexed for example by generalized aminoaciduria, at
blood lead levels across the range of 40 to more than 100 ug/dl. The current lack of evidence
for renal dysfunction at lower blood lead levels in children may simply reflect the greater
clinical concern with neurotoxic effects of lead intoxication in children. The persistence of
lead-induced renal dysfunction in children also remains to be more fully investigated, al-
though a few studies indicate that children diagnosed as being acutely lead poisoned experi-
ence lead nephropathy effects lasting throughout adulthood.
Parallel results from experimental animal studies reinforce the findings in humans and
help illuminate the mechanisms underlying such effects. For example, a number of transient
effects in human and animal renal function are consistent with experimental findings of revers-
ible lesions such as nuclear inclusion bodies, cytomegaly, swollen mitochondria, and increased
numbers of iron-containing lysosomes in proximal tubule cells. Irreversible lesions such as
interstitial fibrosis are also well documented in both humans and animals following chronic
exposure to high doses of lead. Functional renal changes observed in humans have also been
confirmed in animal model systems with respect to increased excretion of ami no acids and
elevated serum urea nitrogen and uric acid concentrations. The inhibitory effects of lead
exposure on renal blood flow and glomerular filtration rate are currently less clear in exper-
imental model systems; further research is needed to clarify the effects of lead on these
functional parameters in animals. Similarly, while lead-induced perturbation of the renin-
angiotensin system has been demonstrated in experimental animal models, further research is
needed to clarify the exact relationships among lead exposure (particularly chronic low-level
exposure), alteration of the renin-angiotensin system, and hypertension in both humans and
animals.
On the biochemical level, it appears that lead exposure produces changes at a number of
sites. Inhibition of membrane marker enzymes, decreased mitochondrial respiratory function/
cellular energy production, inhibition of renal heme biosynthesis, and altered nucleic acid
synthesis are the most marked changes to have been reported. The extent to which these mito-
chondrial alterations occur is probably mediated in part by the intracellular bioavailability
of lead, which is determined by its binding to high affinity kidney cytosolic binding proteins
and deposition within intranuclear inclusion bodies.
Recent studies in humans have indicated that the EDTA lead-mobilization test is the most
reliable technique for detecting persons at risk for chronic nephropathy. Blood lead measure-
ments are a less satisfactory indicator because they may not accurately reflect cumulative
absorption some time after exposure to lead has terminated.
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A number of major questions remain to be more definitively answered concerning the effect
of lead on the kidney. Can a distinctive lead-induced renal lesion be identified either in
functional or histologic terms? What biologic measurements are most reliable for the predic-
tion of lead-induced nephropathy? What is the incidence of lead nephropathy in the general
population as well as among specifically defined subgroups with varying exposure? What is the
natural history of treated and untreated lead nephropathy? What is the mechanism of lead-
induced hypertension and renal injury? What are the contributions of environmental and
genetic factors to the appearance of renal injury due to lead? At what level of lead in blood
can the kidneys be affected? Is there a threshold for renal effects of lead? The most dif-
ficult question to answer may well be to determine the contribution of low levels of lead
exposure to renal disease of non-lead etiologies.
1.12.6 Effects of Lead on Reproduction and Development
Data from human and animal studies indicate that lead may exert gametotoxic, embryotoxic,
and (according to some animal studies) teratogenic effects that may influence the survival and
development of the fetus and newborn. Prenatal viability and development, it appears, may
also be affected indirectly, contributing to concern for unborn children and, therefore, preg-
nant women or childbearing-age women being groups at special risk for lead effects. Early
studies of quite high dose lead exposure in pregnant women indicate toxic—but not tera-
togenic—effects on the conceptus. Effects on reproductive performance in women at lower
exposure levels are not well documented. Unfortunately, currently available human data
regarding lead effects on the fetus during development generally do not lend themselves to
accurate estimation of lowest observed or no-effect levels. However, some studies have shown
that fetal heme synthesis is affected at maternal and fetal blood lead levels as low as
approximately 15 ug/dl, as indicated by urinary ALA levels and ALA-D activity. This observed
effect level is consistent with lowest observed effect levels for indications of altered heme
synthesis seen at later ages for preschool and older children.
There are currently no reliable data pointing to adverse effects in human offspring fol-
lowing paternal exposure to lead, but industrial exposure of men to lead at levels resulting
in blood lead values of 40-50 ug/dl appear to have resulted in altered testicular function.
Also, another study provided evidence of effects on prostatic and seminal vesicle functions at
40-50 ug/dl blood lead levels in lead workers.
The paucity of human exposure data force an examination of the animal studies for indica-
tions of threshold levels for effects of lead on the conceptus. It must be noted that the
animal data are almost entirely derived from rodents. Based on these rodent data, it seems
likely that fetotoxic effects have occurred in animals at chronic exposures to 600-1000 ppm
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lead in the diet. Subtle effects on fetal physiology and metabolism appear to have been ob-
served in rats after chronic maternal exposure to 10 ppm lead in drinking water, while similar
effects of inhaled lead have been seen at chronic levels of 10 ug/m3. With acute exposure by
gavage or by injection, the values are 10-16 mg/kg and 16-30 mg/kg, respectively. Since
humans are most likely to be exposed to lead in their diet, air, or water, the data from other
routes of exposure are of less value in estimating harmful exposures. Indeed, it seems likely
that teratogenic effects occur only when the maternal dose is given by injection.
Although human and animal responses may be dissimilar, the animal evidence does document
a variety of effects of lead exposure on reproduction and development. Measured or apparent
changes in production of or response to reproductive hormones, toxic effects on the gonads,
and toxic or teratogenic effects on the conceptus have all been reported. The animal data
also suggest subtle effects on such parameters as metabolism and cell structure that should be
monitored in human populations. Well designed human epidemiological studies involving large
numbers of subjects are still needed. Such data could clarify the relationship of exposure
levels and durations to blood lead values associated with significant effects, and are needed
for estimation of no-effect levels.
Given that the most clear-cut data concerning the effects of lead on reproduction and
development are derived from studies employing high lead doses in laboratory animals, there is
still a need for more critical research to evaluate the possible subtle toxic effects of lead
on the fetus, using biochemical, ultrastructural, or neurobehavioral endpoints. An exhaustive
evaluation of lead-associated changes in offspring will require consideration of possible
additional effects due to paternal lead burden. Neonatal lead intake via consumption of milk
from lead-exposed mothers may also be a factor at times. Also, it must be recognized that
lead effects on reproduction may be exacerbated by other environmental factors (e.g., dietary
influences, maternal hyperthermia, hypoxia, and co-exposure to other toxins).
1.12.7. Genotoxic and Carcinogenic Effects of Lead
It is difficult to conclude what role lead may play in the induction of human neoplasia.
Epidemiological studies of lead-exposed workers provide no definitive findings. However, sta-
tistically significant elevations in cancer of the respiratory tract and digestive system in
workers exposed to lead and other agents warrant some concern. Since it is clear that lead
acetate can produce renal tumors in some experimental animals, it seems reasonable to conclude
that at least that particular lead compound should be regarded as a carcinogen and prudent to
treat it as if it were also human carcinogen (as per IARC conclusions and recommendations).
However, this statement is qualified by noting that lead has been seen to increase tumorogen-
esis rates in animals only at relatively high concentrations, and therefore does not seem to
be an extremely potent carcinogen. In vitro studies further support the genotoxic and carcin-
ogenic role of lead, but also indicate that lead is not extremely potent in these systems.
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1.12.8. Effects of Lead on the Immune System
Lead renders animals highly susceptible to endotoxins and infectious agents. Host sus-
ceptibility and the humoral immune system appear to be particularly sensitive. As postulated
in recent studies, the macrophage may be the primary immune target cell of lead. Lead-induced
immunosuppression occurs at low lead exposures (blood lead levels in the 20-40 ug/dl range)
that, although they induce no overt toxicity, may nevertheless be detrimental to health.
Available data provide good evidence that lead affects immunity, but additional studies are
necessary to elucidate the actual mechanisms by which lead exerts its immunosuppressive action.
Knowledge of lead effects on the human immune system is lacking and must be ascertained in
order to determine permissible levels for human exposure. However, in view of the fact that
lead affects immunity in laboratory animals and is immunosuppressive at very low dosages, its
potential for serious effects in humans should be carefully considered.
1.12.9 Effects of Lead on Other Organ Systems
The cardiovascular, hepatic, endocrine, and gastrointestional systems generally show
signs of dysfunction mainly at relatively high lead exposure levels. Consequently, in most
clinical and experimental studies attention has been primarily focused on more sensitive and
vulnerable target organs, such as the hematopoietic and nervous systems. However, it should
be noted that overt gastrointestinal symptoms associated with lead intoxication have been
observed in some recent studies to occur in lead workers at blood lead levels as low as 40-
60 ug/dl, suggesting that effects on the gastrointestinal and the other above organ systems
may occur at relatively low exposure levels but remain to be demonstrated by future scientific
investigations.
1.13 EVALUATION OF HUMAN HEALTH RISKS ASSOCIATED WITH EXPOSURE TO LEAD AND ITS COMPOUNDS
1.13.1 Introduction
This section attempts to integrate, concisely, key information and conclusions discussed
in preceding sections into a coherent framework by which interpretation and judgments can be
made concerning the risk to human health posed by present levels of lead contamination in the
United States.
In regard to various health effects of lead, the main emphasis here is on the identifica-
tion of those effects most relevant to various segments of the general U.S. population and the
placement of such effects in a dose-effect/dose-response framework. In regard to the latter,
a crucial issue has to do with relative response of various segments of the population in
terms of effect thresholds as indexed by some exposure indicator. Furthermore, it is of
interest to assess the extent to which available information supports the notion of a conti-
nuum of effects as one proceeds across the spectrum of exposure levels. Finally, it is of
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interest to ascertain the availability of data on the relative number or percentage of members
(i.e., "responders") of specific population groups that can be expected to experience a par-
ticular effect at various lead exposure levels in order to permit delineation of dose-response
curves for the relevant effects in different segments of the population. These matters are
discussed in Sections 1.13.5 and 1.13.6.
Melding of information from the sections on lead exposure, metabolism, and biological
effects permits the identification of population segments at special risk in terms of physio-
logical and other host characteristics, as well as heightened vulnerability to a given effect;
and these risk groups are discussed in Section 1.13.7. With demographic identification of
individuals at risk, one may then draw upon population data from other sources to obtain a
numerical picture of the magnitude of population groups at potential risk. This is also dis-
cussed in Section 1.13.7.
1.13.2 EXPOSURE ASPECTS
1.13.2.1 Levels of Lead in Various Media of Relevance to Human Exposure
Human populations in the United States are exposed to lead in air, food, water, and dust.
In rural areas, Americans not occupationally exposed to lead consume 50 to 75 up; Pb/day. This
level of exposure is referred to as the baseline exposure because it is unavoidable except by
drastic change in lifestyle or by regulation of lead in foods or ambient air. There are
several environmental circumstances that can increase human exposures above baseline levels.
Most of these circumstances involve the accumulation of atmospheric dusts in the work and play
environments. A few, such as pica and family home gardening, may involve consumption of lead
from chips of exterior or interior house paint.
Ambient Air Lead Levels. Monitored ambient air lead concentration values in the U.S. are
contained in two principal data bases: (1) EPA's National Air Sampling Network (NASN),
recently renamed National Filter Analysis Network (NFAN); and (2) EPA's National Aerometric
Data Bank, consistting of measurements by state and local agencies in conjunction with compli-
ance mpnitoring for the current ambient air lead standard.
NASN data for 1982, the most current year in the annual surveys, indicate that most of
the urban sites show reported annual averages be,low 0.7 pg Pb/m3, while the majority of the
non-urban locations have annual figures below 0.2 ug Pb/m3. Over the interval 1976-1981,
there has been a downward trend in these averages, mainly attributable to decreasing lead
content of leaded gasoline and the increasing usage of lead-free gasoline. Furthermore,
examination of quarterly averages over this interval shows a typical seasonal variation,
characterized by maximum air lead values in winter and minimum values in summer.
With respect to the particle size distribution of ambient air lead, EPA studies using
cascade impactors in six U.S. cities have indicated that 60 to 75 percent of such air lead was
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associated with sub-micron particles. This size distribution is significant in considering
the distance particles may be transported and the deposition of particles in the pulmonary
compartment of the respiratory tract. The relationship between airborne lead at the monitor-
ing station and the lead inhaled by humans is complicated by such variables as vertical
gradients, relative positions of the source, monitor, and the person, and the ratio of indoor
to outdoor lead concentrations. To obtain an accurate picture of the amount of lead inhaled
during the normal activities of an individual, personal monitors would probably be the most
effective. But the information gained would be insignificant, considering that inhaled lead
is only a small fraction of the total lead exposure, compared to the lead in food, beverages,
and dust. The critical question with respect to airborne lead is how much lead becomes
entrained in dust. In this respect, the existing monitoring network may provide an adequate
estimate of the air concentration from which the rate of deposition can be determined. The
percentage of ambient air lead which represents alkyl forms was noted in one study to range
from 0.3 to 2.7 percent, rising up to about 10 percent at service stations.
Levels of Lead In Dust. The lead content of dusts can figure prominently in the total
lead exposure picture for young children. Lead in aerosol particles deposited on rigid sur-
faces in urban areas (such as sidewalks, porches, steps, parking lots, etc.) does not undergo
dilution compared to lead transferred by deposition onto soils. Dust can approach extremely
high concentrations. Dust lead can accumulate in the interiors of dwellings as well as in the
outside surroundings, particularly in urban areas.
Measurements of soil lead to a depth of 5 cm in areas of the U.S., using sites near road-
ways, were shown in one study to range from 150 to 500 ug Pb/g dry weight close to roadways
(i.e., within 8 meters). By contrast, lead in dusts deposited on or near heavily traveled
traffic arteries show levels in major U.S. cities ranging up to 8000 ug Pb/g and higher. In
residential areas, exterior dust lead levels are 1000 ug/g or less. Levels of lead in house
dust can be significantly elevated. A study of house dust samples in Boston and New York City
revealed levels of 1000 to 2000 ug Pb/g. Some soils adjacent to houses with exterior lead-
based paints may have lead concentrations greater than 10,000 ug/g.
Thirty-four percent of the baseline consumption of lead by children comes from the con-
sumption of 0.1 g of dust per day (Tables 1-13 and 1-14). Ninety percent of this dust lead is
of atmospheric origin. Dust also accounts for more than ninety percent of the additive lead
attributable to residences in an urban environment or near a smelter (Table 1-15).
Levels of Lead in Food. The route by which adults and older children in the baseline
population of the U.S. receive the largest proportion of lead intake is through foods, with
reported estimates of the dietary lead intake for Americans ranging from 60 to 75 ug/day.
The added exposure from living in an urban environment is about 30 ug/day for adults and 100
ug/day for children, all of which can be attributed to atmospheric lead.
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TABLE 1-13. SUMMARY OF BASELINE HUMAN EXPOSURES TO LEADt
I
t—»
PO
Soil
Source
Child 2-yr old
Inhaled Air
Food
Water & beverages
Dust
Total
Percent
Adult female
Inhaled Air
Food
Water & beverages
Oust
Total
Percent
Adult male
Inahaled air
Food
Water & beverages
Dust
Total
Percent
Total
Lead
Consumed
0.5
28.7
11.2
21.0
61.4
100%
1.0
33.2
17.9
4.5
56.6
100%
1.0
45.7
25.1
4.5
76.3
100%
Percent
of
Total
Consumption
0.8%
46.7
18.3
34.2
1.8%
58.7
31.6
7.9
1.3%
59.9
32.9
5.9
Natural
Lead
Consumed
0.001
0.9
0.01
0.6
1.5
2.4%
0.002
1.0
0.01
0.2
1.2
2.1%
0.002
1.4
0.1
0.2
1.7
2.2%
Indirect
Atmospheric
Lead*
-
0.9
2.1
-
3.0
4.9%
-
1.0
3.4
-
4.4
7.8%
-
1.4
4.7
-
6.1
8.0%
Direct
Atmospheric
Lead*
0.5
10.9
1.2
19.0
31.6
51.5%
1.0
12.6
2.0
2.9
18.5
32.7%
1.0
17.4
2.8
2.9
24.1
31.6%
Lead from
Solder or
Other Metals
-
10.3
7.8
-
18.1
29.5%
-
11.9
12.5
-
24.4
43.1%
-
16.. 4
17.5
-
33.9
44.4%
Lead of
Undetermined
Origin
-
17.6
-
1.4
19.0
22.6%
-
21.6
-
1.4
23.0
26.8%
-
31.5
-
1.4
32.9
27.1%
"Indirect atmospheric lead has been previously incorporated into soil, and will probably remain in the soil for decades or
longer. Direct atmospheric lead has been deposited on the surfaces of vegetation and living areas or incorporated during
food processing shortly before human consumption. It may be assumed that 85 percent of direct atmospheric lead derives
from gasoline additives.
tunits are in ug/day.
-o
TO
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PRELIMINARY DRAFT
TABLE 1-14. RELATIVE BASELINE HUMAN LEAD EXPOSURES EXPRESSED PER KILOGRAM BODY WEIGHT*
Total
Lead
Consumed
Total Lead Consumed
Per Kg Body Wt
pg/Kg-Day
Atmospheric Lead
Per Kg Body Wt
(jg/Kg-Day
Child (2 yr old)
Inhaled air
Food
Water and beverages
Dust
Total
Adult female
Inhaled air
Food
Water and beverages
Dust
Total
Adult male
Inhaled air
Food
Water and beverages
Dust
Total
(ug/day)
0.5
28.7
11.2
21.0
61.4
1.0
33.2
17.9
4.5
56.6
1.0
45.
25.
4.5
76.3
0.05
2.9
1.1
2.1
6.15
0.02
0.66
0.34
0.09
1.13
0.014
0.65
0.36
0.064
1.088
0.05
1.1
0.12
1.9
3.17
0.02
0.25
.04
.06
0.
0.
0.37
0.014
0.25
0.04
0.04
0.344
*Body weights: 2 year old child = 10/kg; adult female = 50 kg; adult male = 70 kg.
Atmospheric lead may be added to food crops in the field or pasture, during transporta-
tion to the market, during processing, and during kitchen preparation. Metallic lead, mainly
solder, may be added during processing and packaging. Other sources of lead, as yet undeter-
mined, increase the lead content of food between the field and dinner table, American
children, adult females, and adult males consume 29, 33 and 46 pg Pb/day, respectively, in
milk and nonbeverage foods. Of these amounts, 38 percent is of direct atmospheric origin, 36
percent is of metallic origin and 20 percent is of undetermined origin.
Processing of foods, particularly canning, can significantly add to their background lead
content, although it appears that the impact of this is being lessened with the trend away
from use of lead-soldered cans. The canning process can increase lead levels 8-to 10-fold
higher than for the corresponding uncanned food items. Home food preparation can also be a
source of additional lead in cases where food preparation surfaces are exposed to moderate
amounts of high-lead household dust.
CHPD1/A 1-127 9/30/83
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TABLE 1-15. SUMMARY OF POTENTIAL ADDITIVE EXPOSURES TO LEAD
Baseline exposure:
Child (2 yr old)
Inhaled air
Food, water & beverages
Dust
Total baseline
Additional exposure due to:
urban atmospheres:1
air inhalation
dust
family gardens2
interior lead paint3
residence near smelter:4
air inhalation
dust
secondary occupational5
Baseline exposure:
Adult Male
Inhaled air
Food, water & beverages
Dust
Total baseline
Additional exposure due to:
urban atmospheres:1
air inhalation
dust
family gardens2
interior lead paint3
residence near smelter:4
air inhalation
dust
occupational6
secondary occupational6
smoking
wine consumption
Total
Lead
Consumed
(ug/day)
0.5
39.9
21.0
61.4
7
72
800
65
60
2250
150
1.0
70.8
4.5
76.3
14
7
2000
17
120
250
1100
21
30
100
Atmospheric
Lead
Consumed
(ug/day)
0.5
12.1
19.0
31.6
7
71
200
-
60
2250
-
1.0
20.2
2.9
24.1
14
7
500
-
120
250
1100
-
27
?
Other
Lead
Sources
(ug/day)
-
27.8
2.0
29.8
0
1
600
85
-
-
-
-
50.6
1.6
52.2
-
-
1500
17
-
-
-
-
3
?
>includes lead from household and street dust (1000 MO/9) and inhaled air (.75 ug/ms)
2assumes soil lead concentration of 2000 ug/g; all fresh leafy and root vegetables, sweet
corn of Table 7-15 replaced by produce from garden. Also assumes 25X of soil lead is of
atmospheric origin.
'assumes household dust rises from 300 to 2000 ug/g. Oust consumption remains the same as
baseline. Does not include consumption of paint chips.
'assumes household and street dust increases to 25,000 ug/g, Inhaled air increases to 6
Mfl/"3-
sassumes household dust increases to 2400 ug/g.
'assumes 8 hr shift at 10 ug Pb/m3 or 90X efficiency of respirators at 100 ug/ Pb/m*. and
occupational dusts at 100,000 ug/m3.
CHPD1/A
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Lead Levels in Drinking Water. Lead in drinking water may result from contamination of
the water source or from the use of lead materials in the water distribution system. Lead
entry into drinking water from the latter is increased in water supplies which are plumbo-
solvent, i.e., with a pH below 6.5. Exposure of individuals occurs through direct ingestion
of the water or via food preparation in such water.
The interim EPA drinking water standard for lead is 0.05 ug/g (50 UQ/1) and several
extensive surveys of public water supplies indicate that only a limited number of samples ex-
ceeded this standard on a nationwide basis. For example, a survey of interstate carrier water
supplies conducted by EPA showed that only 0.3 percent exceeded the standard.
The major source of lead contamination of drinking water is the distribution system it-
self, particularly in older urban areas. Highest levels are encountered in "first-draw" sam-
ples, i.e., water sitting in the piping system for an extended period of time. In a large
community water supply survey of 969 systems carried out in 1969-1970, it was found that the
prevalence of samples exceeding 0.05 ug/g was greater where water was plumbo-solvent.
Most drinking water, and the beverages produced from drinking water, contain 0.008 to
0.02 ug Pb/g. The exceptions are canned juices and soda pop, which range from 0.033 to 0.052
ug/g. About 11 percent of the lead consumed in drinking water and beverages is of direct
atmospheric origin, 70 percent comes from solder and other metals.
Lead in Other Media. Flaking lead paint in deteriorated housing stock in urban areas of
the Northeast and Midwest has long been recognized as a major source of lead exposure for
young children residing in this housing stock, particularly for children with pica. Indivi-
duals who are cigarette smokers may inhale significant amounts of lead in tobacco smoke. One
study has indicated that the smoking of 30 cigarettes daily results in lead intake equivalent
to that of inhaling lead in ambient air at a level of 1.0 ug Pb/m3.
Cumulative Human Lead Intake From Various Sources. Table 1-13 shows the baseline of
human lead exposures as described in detail in Chapter 7. These data show that atmospheric
lead accounts for at least 30 percent of the baseline adult consumption and 50 percent of the
daily consumption by a 2 yr old child. These percentages are conservative estimates because a
part of the lead of undetermined origin may originate from atmospheric lead not yet accounted
for.
From Table 1-14, it can be seen that young children have a dietary lead intake rate, that
is 5-fold greater than for adults, on a body weight basis. To these observations must be
added that absorption rates for lead are higher in children than in adults by at least 3-fold.
Overall, then, the rate of lead entry into the blood stream of children, on a body weight
basis, is estimated to be twice that of adults from the respiratory tract and 6 and 9 times
greater from the GI tract. Since children consume more dust than adults, the atmospheric
fraction of the baseline exposure is ten-fold higher for children than for adults, on a body
CHPD1/A 1-129 9/30/83
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weight basis. These differences generally tend to place young children at greater risk, in
terms of relative amounts of proportions of atmospheric lead absorbed per kg body weight, than
adults under any given lead exposure situation.
1.13.3 LEAD METABOLISM: KEY ISSUES FOR HUMAN HEALTH RISK EVALUATION
From the detailed discussion of those various quantifiable characteristics of lead toxi-
cokinetics in humans and animals presented in Chapter 10, several clear issues emerge as being
important for full evaluation of the human health risk posed by lead:
(1) Differences in systemic or internal lead exposure of groups within the general popu-
lation in terms of such factors as age/development and nutritional status; and
(2) The relationship of indices of internal lead exposures to both environmental levels
of lead and tissues levels/effects.
Item 1 provides the basis for identifying segments within human populations at increased
risk in terms of exposure criteria and is used along with additional information on relative
sensitivity to lead health effects for identification of risk populations. The chief concern
with item 2 is the adequacy of current means for assessing internal lead exposure in terms of
providing adequate margins of protection from lead exposures producing health effects of con-
cern.
1.13.3.1 Differential Internal Lead Exposure Within Population Groups
Compared to adults, young children take in more lead through the gastrointestinal and
respiratory tracts on a unit body weight basis, absorb a greater fraction of this lead intake,
and also retain a greater proportion of the absorbed amount.
Unfortunately, such amplification of these basic toxicokinetic parameters in children vs.
adults also occurs at the time when: (1) humans are developmentally more vulnerable to the
effects of toxicants such as lead in terms of metabolic activity, and (2) the interactive re-
lationships of lead with such factors as nutritive elements are such as to induce a negative
course toward further exposure risk.
Typical of physiological differences in children vs. adults in terms of lead exposure im-
plications is a more metabolically active skeletal system in children. In children, turnover
rates of bone elements such as calcium and phosphorus are greater than in adults, with corre-
spondingly greater mobility of bone-sequestered lead. This activity is a factor in the obser-
vation that the skeletal system of children is relatively less effective as a depository for
lead than in adults.
Metabolic demand for nutrients, particularly calcium, iron, phosphorus, and the trace
nutrients, is such that widespread deficiencies of these nutrients exist, particularly among
poor children. The interactive relationships of these elements with lead are such that defi-
CHPD1/A 1-130 9/30/83
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ciency states both enhance lead absorption/retention and, as in the case of lead-induced
reductions in 1,25-dihydroxyvitamin D, establish increasingly adverse interactive cycles.
Quite apart from the physiological differences which enhance internal lead exposure in
children is the unique relationship of 2- to 3-year-olds to their exposure setting by way of
normal mouthing behavior and the extreme manifestation of this behavior, pica. This behavior
occurs in the same age group which studies have consistently identified as having a peak in
blood lead. A number of investigations have addressed the quantification of this particular
route of lead exposure, and it is by now clear that such exposure will dominate other routes
when the child's surroundings, e.g., dust and soil, are significantly contaminated by lead.
Information provided in Chapter 10 also makes it clear that lead traverses the human pla-
centa! barrier, with lead uptake by the fetus occurring throughout gestation. Such uptake of
lead poses a potential threat to the fetus via an impact on the embryological developement of
the central nervous and other systems. Hence, the only logical means of protecting the fetus
from lead exposure is exposure control during pregnancy.
Within the general population, then, young children and pregnant women qualify as defin-
ale risk groups for lead exposure. Occupational exposure to lead, particularly among lead
workers, logically defines these individuals as being in a high-risk category; work place con-
tact is augmented by those same routes and levels of lead exposure affecting the rest of the
adult population. From a biological point of view, lead workers do not differ from the gene-
ral adult population with respect to the various toxicokinetic parameters and any differences
in exposure control--occupational vs. non-occupational populations—as they exist are based on
factors other than toxicokinetics.
1.13.3.2 Indices of Internal Lead Exposure and Their Relationship To External Lead Levels and
Tissue Burdens/Effects
.Several points are of importance in this area of lead toxicokinetics. They are: (1) the
temporal characteristics of indices of lead exposure; (2) the relationship of the indicators
to external lead levels; (3) the validity of indicators of exposure in reflecting target tis-
sue burdens; (4) the interplay between these indicators and lead in body compartments; and
(5) those various aspects of the issue with particular reference to children.
At this time, blood lead is widely held to be the most convenient, if imperfect, index of
both lead exposure and relative risk for various adverse health effects. In terms of ex-
posure, however, it is generally accepted that blood lead is a temporally variable measure
which yields an index of relatively recent exposure because of the rather rapid clearance of
absorbed lead from the blood. Such a measure, then, is of limited usefulness in cases where
exposure is variable or intermittent over time, as is often the case with pediatric lead ex-
posure.
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Mineralizing tissue, specifically deciduous teeth, accumulate lead over time in propor-
tion to the degree of lead exposure, and analysis of this material provides an assessment
integrated over a greater time period and of more value in detecting early childhood exposure.
These two methods of assessing internal lead exposure have obvious shortcomings. A blood
lead value will say little about any excessive lead intake at early periods, even though such
remote exposure may have resulted in significant injury. On the other hand, whole tooth or
dentine analysis is retrospective in nature and can only be done after the particularly vulne-
rable age in children under 4 to 5 years-- has passed. Such a measure, then provides little
utility upon which to implement regulatory policy or clinical intervention.
The dilemmas posed by these existing methods may be able to be resolved by j_n situ analy-
sis of teeth and bone lead, such that the intrinsic advantage of mineral tissue as a cumula-
tive index is combined with measurement which is temporally concordant with on-going exposure.
Work in several laboratories offers promise for such iji situ analysis (See Chapters 9 and 10).
A second issue concerning internal indices of exposure and environmental lead is the
relationship of changes in lead content of some medium with changes in blood content. Much of
Chapter 11 was given over to description of the mathematical relationships of blood lead with
lead in some external medium— air, food, water, etc., without consideration of the biological
underpinnings for these relationships.
Over a relatively broad range of lead exposure through some medium, the relationship of
lead in the external medium to blood lead is curvilinear, such that relative change in blood
lead per unit change in medium level generally becomes increasingly less as exposure increases.
This behavior may reflect changes in tissue lead kinetics, reduced lead absorption, or in-
creased excretion. Limited animal data would suggest that changes in excretion or absorption
are not factors in this phenomenon. In any event, modest changes in blood levels with expo-
sure at the higher end of this range are in no way to be taken as reflecting concomitantly
modest changes in body or tissue lead uptake. Evidence continues to accumulate which suggests
that an indicator such as blood lead is an imperfect measure of tissue lead burdens and of
changes in such tissue levels in relation to changes in external exposure.
In Chapter 10, it was pointed out that blood lead is logarithmically related to chelata-
ble lead (the latter being a more useful measure of the potentially toxic fraction of body
lead), such that a unit change in blood lead is associated with an increasingly larger amount
of chelatable lead. One consequence of this relationship is that moderately elevated blood
lead values will tend to mask the "margin of safety" in terms of mobile body lead burdens.
Such masking is apparent in one study of children where chelatable lead levels in children
showing moderate elevations in blood lead overlapped those obtained in subjects showing frank
plumbism, i.e. overt lead intoxication.
CHPD1/A 1-132 9/30/83
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PRELIMINARY DRAFT
Related to the above is the question of the source of chelatable lead. It was noted in
Chapter 10 that some sizable fraction of chelatable lead is derived from bone and this compels
reappraisal of the notion that bone is an "inert sink" for otherwise toxic body lead. The no-
tion of bone lead as toxicologically inert never did accord with what was known from studies
of bone physiology, i.e., that bone is a "living" organ, and the thrust of recent studies of
chelatable lead (as well as interrelationships of lead and bone metabolism) is toward bone
lead being viewed as actually an insidious source of long-term systemic lead exposure rather
than a protective mechanism permitting significant lead contact in industrialized populations.
The complex interrelationships of lead exposure, blood lead, and lead in body compart-
ments is of particular interest in considering the disposition of lead in young children.
Since children take in more lead on a weight basis, and absorb and retain more of this lead
than the adult, one might expect that either tissue and blood levels would be significantly
elevated or that the child's skeletal system would be more efficient in lead sequestration.
Blood lead levels in young children are either similar to adults (males) or somewhat
higher (adult females). Limited autopsy data, furthermore, indicate that soft tissue levels
in children are not markedly different from adults, whereas the skeletal system shows an
approximate 2-fold increase in lead concentration from infancy to adolescence. Neglected in
this observation is the fact that the skeletal system in children grows at an exponential
rate, so that skeletal mass increases 40-fold during the interval in childhood when bone lead
levels increase 2-fold, resulting in an actual increase of approximately 80-fold in total ske-
letal lead. If the skeletal growth factor is taken into account, along with growth in soft
tissue and the expansion of vascular fluid volumes, the question of lead disposition in
children is better understood.
Finally, limited animal data indicate that blood lead alterations with changes in lead
exposure are poor indicators of such changes in target tissue. Specifically, it appears that
abrupt reduction of lead exposure will be more rapidly reflected in blood lead than in such
target tissues as the central nervous system, especially in the developing organism. This
discordance may underlie the observation that severe lead neurotoxicity in children is assoc-
iated with a rather broad range of blood lead values (see Section 1.12.4).
The above discussion of some of the problems with the use of blood lead in assessing tar-
get tissue burdens or the toxicologically active fraction of total body lead highlights the
the inherent toxicokinetic problems with use of blood lead levels in defining margins of safe-
ty for avoiding internal lead exposure levels associated with undue risk of adverse effects.
If, for example, blood lead levels of 40-50 ug/dl in "asymptomatic" children are associated
with chelatable lead burdens which overlap those encountered in frank pediatric plumbism, as
documented in one series of lead-exposed children, then there is no margin of safety at these
blood levels for severe effects which are not at all a matter of controversy. Were it both
CHPD1/A 1-133 9/30/83
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PRELIMINARY DRAFT
logistically feasible to do so on a large scale and were the use of chelants free of health
risk to the subjects, serial provocative chelation testing would appear to be the better indi-
cator of exposure and risk. Failing this, the only prudent alternative is the use of a large
safety factor applied to blood lead which would translate to an "acceptable" chelatable bur-
den. It is likely that this blood lead value would lie well below the currently accepted up-
per limit of 30 pg/dl, since the safety factor would have to be large enough to protect
against frank plumbism as well as more subtle health effects seen with non-overt lead intoxi-
cation. This rationale from the standpoint of lead toxicokinetics is in accord also with the
growing data base for dose -effect relationships of lead's effects on heme biosynthesis,
erythropoiesis, and the nervous system in humans as summarized in Sections 1.12.3 and 1.12.4.
The future developement and routine use of i_n situ mineral tissue testing at time points
concordant with on-going exposure and the comparison of such results with simultaneous blood
lead and chelatable lead measurement would be of significant value in further defining what
level of blood lead is indeed an acceptable upper limit.
1.13.3.3 Proportional Contributions of Lead in Various Media to Blood Lead in Human
Populations
The various mathematical descriptions of the relationship of blood lead to lead in indi-
vidual media—air, food, water, dust, soil—were discussed in some detail in Chapter 11 and
summarized concisely in a preceding section (1.11) of this chapter. Using values for lead
intake/content of those media which appear to represent the current exposure picture for human
populations in the U.S., those relationships are further employed in this section to estimate
proportional inputs to total blood lead levels in U.S. populations. Such an exercise is of
help in providing an overall perspective on which routes of exposure are of most significance
in terms of contributions to blood lead levels seen in U.S. populations.
Table 1-16 tabulates the relative direct contributions (in percentages) of air lead to
blood lead at different air-lead levels for calculated typical background levels of lead from
food and water in adults. The blood lead contributions from diet are estimated using the
slope 0.02 u9/dl increase in blood lead ug/day intake as discussed in Section 1.11.3. In
Table 1-17 are listed direct contributions of air lead to blood lead at varying air lead
levels for children, given calculated typical background levels of blood lead derived from
food and water as per the work of Ryu et-al. (1983). Table 1-18 shows relative contributions
of dust/soil to blood lead at varying dust/soil levels for children given calculated back-
ground levels of blood lead from air, food, and water. Assuming that virtually all soil/dust
lead is due to atmospheric fallout of lead particles, the percentage contribution of air lead
directly and indirectly to blood lead becomes significantly greater than when considering just
the direct impact of inhaling lead in the ambient air.
CHPD1/A 1-134 9/30/83
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PRELIMINARY DRAFT
TABLE 1-16. DIRECT CONTRIBUTIONS OF AIR LEAD TO BLOOD LEAD (PbB)
IN ADULTS AT FIXED INPUTS OF WATER AND FOOD LEAD
Air Lead
(ug/m3)
0.1
1.0
1.5
3 A PbB, . , fl
PbB (Air)a
0.2
2.0
3.0
for 3.2 un/m3 or
PbB (Food)b
2.0
2.0
2.0
less.
PbB (Water)0
0.6
0.6
0.6
% PbB
From Air
7.1
43.*
53.5
A Pb Air
^Assuming 100 pg/day lead from diet and slope 0.02 as discussed in Section 11.4.2.4.
Assuming 10 ug/Ł water, Pocock et al. (1983).
TABLE 1-17. DIRECT CONTRIBUTIONS OF AIR LEAD TO BLOOD LEAD IN CHILDREN AT
FIXED INPUTS OF FOOD AND WATER LEAD
Air Lead
(ug/m3)
0.1
0.5
1.0
1.5
2.5
PbB (Air)a
0.2
1.0
2.0
3.0
5.0
L.
PbB (Food)0
16.0
16.0
16.0
16.0
16.0
PbB (Water)0
0.6
0.6
0.6
0.6
0.6
% PbB
From Air
1.2
5.7
10.8
15.3
23.1
-^p{^r=2.0for3.2ug/m3 or less.
Assuming 100 ug Pb/day based upon Ryu et al. (1983).
cAssuming 10 ug Pb/1 water, using Pocock et al. (1983).
TABLE 1-18. CONTRIBUTIONS OF DUST/SOIL LEAD TO BLOOD LEAD IN CHILDREN AT
FIXED INPUTS OF AIR, FOOD, AND WATER LEAD
Dust-Soil
500
1000
2000
a A PbB
Air Lead
ug/m3
0.5
0.5
0.5
>.f> for 3.2 i
PbB a
(Air)a
1.0
1.0
1.0
jo7m3 or IP
PbB .
(Food)0
16.0
16.0
16.0
>SS.
PbB
(Water)0
0.6
0.6
0.6
PbB .
(Dust-Soil )a
0.3/3.4
0.6/6.8
1.2/13.6
% PbB
From Dust/Soil
1.7/16.2
3.3/27.8
6.4/43.6
A Pb Air
Assuming 100 .ug Pb/day based on Ryu et al. (1983).
cAssuming 10 ug Pb/1 water, based on Pocock et al. (1983).
dBased on range 0.6 to 6.8 ug/dl for 1000 ug/g (Angle and Mclntire, 1979).
CHP01/A 1-135
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1.13.4 BIOLOGICAL EFFECTS OF LEAD RELEVANT TO THE GENERAL HUMAN POPULATION
It is clear from the wealth of available literature reviewed in Chapter 12, that there
exists a continuum of biological effects associated with lead across a broad range of expo-
sure. At rather low levels of lead exposure, biochemical changes, e.g., disruption of certain
enzymatic activities involved in heme biosynthesis and erythropoietic pyrimidine metabolism,
are detectable. Heme biosynthesis is a generalized process in mammalian species, including
man, with importance for normal physiological functioning of virtually all organ systems.
With increasing lead exposure, there are sequentially more intense effects on heme synthesis
and a broadening of lead effects to additional biochemical and physiological mechanisms in
various tissues, such that increasingly more severe disruption of the normal functioning of
many different organ systems becomes apparent. In addition to heme biosynthesis impairment at
relatively low levels of lead exposure, disruption of normal functioning of the erythropoietic
and the nervous systems are among the earliest effects observed as a function of increasing
lead exposure. With increasingly intense exposure, more severe disruption of the erythropoie-
tic and nervous systems occur and additional organ systems are affected so as to result, for
example, in the manifestation of renal effects, disruption of reproductive functions, and im-
pairment of immunological functions. At sufficiently high levels of exposure, the damage to
the nervous system and other effects can be severe enough to result in death or, in some cases
of non-fatal lead poisoning, long-lasting sequelae such as permanent mental retardation.
As discussed in Chapter 12 of this document, numerous new studies, reviews, and critiques
concerning Pb-related health effects have been published since the issuance of the earlier EPA
lead criteria document in 1977. Of particular importance for present criteria development
purposes are those new findings, taken together with information earlier available at the
writing of the 1977 Criteria Document, which have bearing, on the establishment of quantitative
dose-effect or dose-response relationships for biological effects of lead potentially viewed
as adverse health effects likely to occur among the general population at or near existing
ambient air concentrations of lead in the United States. Key information regarding observed
health effects and their implications are discussed below for adults and children.
For the latter group, children, emphasis is placed on the discussion of (1) heme biosyn-
thesis effects, (2) certain other biochemical and hematological effects, and (3) the disrup-
tion of nervous system functions. All of these appear to be among those effects of most con-
cern for potential occurrence in association with exposure to existing U.S. ambient air lead
levels of the population group (i.e., children Ł6 years old) at greatest risk for lead-induced
health effects. Emphasis is also placed on the delineation of internal lead exposure levels,
as defined mainly by blood-lead (PbB) levels, likely associated with the occurrence of such
effects. Also discussed are characteristics of the subject effects that are of crucial impor-
CHPD1/A 1-136 9/30/83
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PRELIMINARY DRAFT
tance in regard to the determination of which might reasonably be viewed as constituting
"adverse health effects" in affected human populations.
1.13.4.1 Criteria for Defining Adverse Health Effects. Over the years, there has been super-
imposed on the continuum of lead-induced biological effects various judgments as to which
specific effects observed in man constitute "adverse health effects". Such judgments involve
not only medical concensus regarding the health significance of particular effects and their
clinical management, but also incorporate societal value judgments. Such societal value judg-
ments often vary depending upon the specific overall contexts to which they are applied, e.g.,
in judging permissible exposure levels for occupational versus general population exposures to
lead. For some lead exposure effects, e.g., severe nervous system damage resulting in death
or serious medical sequelae consequent to intense lead exposure, there exists little or no
disagreement as to these being significant "adverse health effects." For many other effects
detectable at sequentially lower levels of lead exposure, however, the demarcation lines as to
which effects represent adverse health effects and the lead exposure levels at which they are
accepted as occurring are neither sharp nor fixed, having changed markedly during the past
several decades. That is, from a historical perspective, levels of lead exposure deemed to be
acceptable for either occupationally exposed persons or the general population have been
steadily revised downward as more sophisticated biomedical techniques have revealed formerly
unrecognized biological effects and concern has increased in regard to the medical and social
significance of such effects.
It is difficult to provide a definitive statement of all criteria by which specific bio-
logical effects associated with any given agent can be judged to be "adverse health effects".
Nevertheless, several criteria are currently well-accepted as helping to define which effects
should be viewed as "adverse". These include: (1) impaired normal functioning of a specific
tissue or organ system itself; (2) reduced reserve capacity of that tissue or organ system in
dealing with stress due to other causative agents; (3) the reversibility/irreversibility of
the particular effect(s); and (4) the cumulative or aggregate impact of various effects on
individual organ systems on the overall functioning and well-being of the individual.
Examples of possible uses of such criteria in evaluating lead effects can be cited for
illustrative purposes. For example, impairment of heme synthesis intensifies with increasing
lead exposure until hemeprotein synthesis is inhibited in many organ systems, leading to re-
ductions in such functions as oxygen transport, cellular energetics, and detoxification of
xenobiotic agents. The latter effect can also be cited as an example of reduced reserve capa-
city pertinent to consideration of effects of lead, the reduced capacity of the liver to deto-
xify certain drugs or other xenobiotic agents resulting from lead effects on hepatic detoxifi-
cation enzyme systems.
CHPD1/A 1-137 9/30/83
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PRELIMINARY DRAFT
In regard to the issue of reversibility/irreversibility of lead effects, there are really
two dimensions to the issue that need to be considered, i.e.: (1) biological reversibility or
irreversibility characteristic of the particular effect in a given organism; and (2) the gene-
rally less-recognized concept of exposure reversibility or irreversibility. Severe central
nervous system damage resulting from intense, high level lead exposure is generally accepted
as an irreversible effect of lead exposure; the reversibility/irreversibility of certain more
difficult-to-detect neurological effects occurring at lower lead exposure levels, however,
remains a matter of some controversy. The concept of exposure reversibility/irreversibility
can be illustrated by the case of urban children of low socioecomomic status showing dis-
turbances in heme biosynthesis and erythropoiesis. Biologically, these various effects may be
considered reversible; the extent to which actual reversibility occurs, however, is determined
by the feasibility of removing these subjects from their particular lead exposure setting. If
such removal from exposure is unlikely or does not occur, then such effects will logically
persist and, defacto, constitute essentially irreversible effects.
1.13.4.2 Dose-Effect Relationships for Lead-Induced Health Effects
Human Adults. Table 1-19 concisely summarizes the lowest observed effect levels (in
terms of blood lead concentrations) thus far credibly associated with particular health ef-
fects of concern for human adults in relation to specific organ systems or generalized physio-
logical processes, e.g. heme synthesis.
The most serious effects associated with markedly elevated blood lead levels are severe
neurotoxic effects that include irreversible brain damage as indexed by the occurrence of
acute or chronic encephalopathic symptoms observed in both humans and experimental animals.
For most human adults, such damage typically does not occur until blood lead levels exceed
100-120 |J9/dl- Often associated with encephalopathic symptoms at such blood lead levels or
higher are severe gastrointestinal symptoms and objective signs of effects on several other
organ systems as well. The precise threshold for occurrence of overt neurological and gastro-
intestinal signs and symptoms of lead intoxication remains to be established but such effects
have been observed in adult lead workers at blood lead levels as low as 40-60 ug/dl, notably
lower than the 60 or 80 ug/dl levels previously established or discussed as being "safe" for
occupational lead exposure.
Other types of health effects occur coincident with the above overt neurological and gas-
trointestinal symptoms indicative of marked lead intoxication. These range from frank peri-
pheral neuropathies to chronic renal nephropathy and anemia. Toward the lower range of blood
lead levels associated with overt lead intoxication or somewhat below, less severe but impor-
tant signs of impairment in normal physiological functioning in several organ systems are
evident, including: (1) slowed nerve conduction velocities indicative of peripheral nerve
CHPD1/A 1-138 9/30/83
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TABLE 1-19. SUMMARY OF LOWEST OBSERVED EFFECT LEVELS FOR KEY LEAD-INDUCED HEALTH EFFECTS IN ADULTS
Lowest Observed
Effect Level (PbB)
100-120 Mg/dl
80 Mg/dl
60 Mg/dl
50 Mg/dl
to 40 MS/dl
30 Mg/dl
25-30 Mg/dl
15-20 Mg/dl
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PRELIMINARY DRAFT
dysfunction (at 30-40 ug/dl, or possibly lower levels); (2) altered testicular function (at
40-50 ug/dl); and (3) reduced hemoglobin production (at approximately 50 ug/dl) and other
signs of impaired heme synthesis evident at still lower blood lead levels. All of these ef-
fects point toward a generalized impairment of normal physiological functioning across several
different organ systems, which becomes abundantly evident as adult blood lead levels approach
or exceed 30-40 ug/dl. Evidence for impaired heme synthesis effects in blood cells exists at
still lower blood lead levels in human adults and the significance of this and evidence of
impairment of other biochemical processes important in cellular energetics are the subject of
discussion below in relation to health effects observed in children.
Children. Table 1-20 summarizes lowest observed effect levels for a variety of imporatnt
health effects observed in children. Again, as for adults, it can be seen that lead impacts
many different organ systems and biochemical/physiological processes across a wide range of
exposure levels. Also, again, the most serious of these effects is the severe, irreversible
central nervous system damage manifested in terms of encephalopathic signs and symptoms. In
children, effective blood lead levels for producing encephalopathy or death are lower than for
adults, starting at approximately 80-100 ug/dl. Other overt neurological symptoms are evident
at somewhat lower blood lead levels associated with lasting neurological sequalae. Colic and
other overt gastrointestinal symptoms clearly occur at similar or still lower blood lead
levels in children, at least down to 60 ug/dl and, perhaps, below. Renal dysfunction is also
manifested along with the above overt signs of lead intoxication in children and has been
reported at blood lead levels as low as 40 ug/dl in some pediatric populations. Frank anemia
is also evident at 70 ug/dl, representing an extreme manifestation of reduced hemoglobin syn-
thesis observed at blood lead levels as low as 40 ug/dl along with other signs of marked heme
synthesis inhibition at that exposure level. Again, all.of these effects are reflective of
widespread impact of lead on the normal physiological functioning of many different organ
systems in children at blood lead levels at least as low as 40 pg/dl.
Among the most important and controversial of the issues discussed in Chapter 12 are the
evaluation of neuropsychological or electrophysiological effects associated with low-level
lead exposures in non-overtly lead intoxicated children. None of the available studies on the
subject, individually, can be said to prove conclusively that significant neurological effects
occur in children at blood-Pb levels <30 pg/dl. The collective neurobehavioral studies of CNS
(cognitive; IQ) effects, for example, can probably now be most reasonably interpreted as most
clearly being indicative of a likely association between neuropsychologic deficits and low-
level Pb-exposures in young children resulting in blood-Pb levels of approximately 30 to 50
ug/dl. However, due to specific methodological problems with each of the various studies (as
noted in Chapter 12), much caution is warranted that precludes conclusive acceptance of the
CHPD1/A 1-140 9/30/83
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TABLE 1-20. SUMMARY OF LOWEST OBSERVED EFFECT LEVELS FOR KEY LEAD-INDUCED HEALTH EFFECTS IN CHILDREN
Lowest Observed
Effect Level (PbB)
80-100 ug/dl
70
60
WV
,_« 50
S 40
30
15-20
10
ug/dl
ug/dl
ug/dl
ug/dl
ug/dl
Heme Synthesis and Neurological
Hematological Effects Effects
Encepha 1 opath i c
signs and symptoms
Frank anemia
I'
Reduced hemoglobin Cognitive (CN5) deficts
Elevated coproporphy r i n Peripheral nerve dysfunction
(slowed NCV's)
Increased urinary ALA
« ^
Erythrocyte protoporphyin CNS electrophysiological
elevation deficits
ALA-0 inhibition ?
1
Renal System Gastrointestinal Other Biochemical
Effects Effects Effects
Renal dys- Colic, other overt
function gastrointestinal symptoms
(aminoaciduria) i
i
Vitamin 0 metabolism
interference
Py-5-N activity
inhibition
-D
70
70
Abbreviations: PbB = blood lead concentrations; Py-5-N = pyrimidine-S'-nucleotidase.
-------
PRELIMINARY DRAFT
observed effects being due to Pb rather than other (at times uncontrolled for) potentially
confounding variables.
Also of considerable importance are studies by which provide evidence of changes in EEC
brain wave patterns and CMS evoked potential responses in non-overtly lead intoxicated chil-
dren experiencing relatively low blood-Pb levels. Sufficient exposure information was pro-
vided by these studies and appropriate statistical analyses were carried out which demonstra-
ted clear, statistically significant associations between electrophysiological (SW voltage)
changes and blood-Pb levels in the range of 30 to 55 |jg/dl and probable analogous associations
at blood-Pb levels below 30 ug/dl (with no evident threshold down to 15 ug/dl). In this case,
the continued presence of such electrophysiological changes upon follow-up two years later,
suggests persistence of such effects even in the face of later declines in blood-Pb levels
and, therefore, possible non-reversibility of the observed electrophysiological CNS changes.
However, the reported electrophysiological effects were not found to be significantly assoc-
iated with IQ decrements.
The precise medical or health significance of the neuropsychological and electrophysiolo-
gical effects found by the above studies to be associated with low-level Pb-exposures is dif-
ficult to state with confidence at this time. The IQ deficits and other behavioral changes,
although statistically significant, are generally relatively small in magnitude as detected by
the reviewed studies, but nevertheless may still impact the intellectual development, school
performance, and social development of the affected children sufficiently so as to be regarded
as adverse. This would be especially true if such impaired intellectual development or school
performance and disrupted social development were reflective of persisting, long-term effects
of low-level lead exposure in early childhood. The issue of persistence of such lead effects,
however, remains to be more clearly resolved, with some study results reviewed in Chapter 12
and mentioned above suggesting that significant low-level Pb-induced neurobehavioral and EEC
effects may, in fact, persist into later childhood.
In regard to additional studies reviewed in Chapter 12 concerning the neurotoxicity of
lead, certain evidence exists which suggests that neurotoxic effects may be associated with
lead-induced altered heme synthesis, which results in an accumulation of ALA in brain affec-
ting CNS GABA synthesis, binding, and/or inactivation by neuronal reuptake after synaptic
release. Also, available experimental data suggest that these effects may have functional
-significance in the terms of this constituting one mechanism by which lead may increase the
sensitivity of rats to drug-induced seizures and, possibly, by which GABA-related behavioral
or physiological control functions are disrupted. Unfortunately, the available research data
do not allow credible direct estimates of blood-lead levels at which such effects might occur
in rats, other non-human mammalian species, or man. Inferentially, however, one can state
CHPD1/A 1-142 9/30/83
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PRELIMINARY DRAFT
that threshold levels for any marked lead-induced ALA impact on CNS GABA mechanisms are most
probably at least as high as blood-lead levels at which significant accumulations of ALA have
been detected in erythrocytes or non-blood soft tissues (see below). Regardless of any dose-
effect levels inferred, though, the functional and/or medical significance of lead-induced ALA
effects on CNS mechanisms at low-levels of lead-exposure remains to be more fully determined
and cannot, at this time, be unequivocably seen as an adverse health effect.
Research concerning lead-induced effects on heme synthesis, also provides information of
importance in evaluating whether significant health effects in children are associated with
blood-lead levels below 30 ug/dl. As discussed earlier, lead affects heme synthesis at
several points in its metabolic pathway, with consequent impact on the normal functioning of
many body tissues. The activity of the enzyme, ALA-S, catalyzing the rate-limiting step of
heme synthesis does not appear to be significantly affected until blood-lead levels reach or
exceed approximately 40 ug/dl. The enzyme ALA-D, which catalizes the conversion of ALA to
porphobilinogen as a further step in the heme biosynthetic pathway, appears to be affected at
much lower blood-lead levels as indexed directly by observations of ALA-D inhibition or indi-
rectly in terms of consequent accumulations of ALA in blood and non-blood tissues. More
specifically, inhibition of erythrocyte ALA-D activity has been observed in humans and other
mammalian species at blood-lead levels even below 10 to 15 ug/dl, with no clear threshold evi-
dent. Correlations between erythrocyte. and hepatic ALA-D activity inhibition in lead workers
at blood-lead levels in the range of 12 to 56 ug/dl suggest that ALA-D activity in soft tis-
sues (eg. brain, liver, kidney, etc.) may be inhibited at similar blood-lead levels at which
erythrocyte ALA-D activity inhibition occurs, resulting in accumulations of ALA in both blood
and soft tissues.
It is now clear that significant increases in both blood and urinary ALA occur below the
currently commonly-accepted blood-lead level of 40 ug/dl and, in fact, such increases in blood
and urinary ALA are detectable in humans at blood-lead levels below 30 ug/dl, with no clear
threshold evident down to 15 to 20 ug/dl. Other studies have demonstrated significant eleva-
tions in rat brain, spleen and kidney ALA levels consequent to acute or chronic lead-exposure,
but no clear blood-lead levels can yet be specified at which such non-blood tissue ALA in-
creases occur in humans. It is reasonable to assume, however, that ALA increases in non-blood
tissues likely begin to occur at roughly the same blood-lead levels associated with increases
in erythrocyte ALA levels.
Lead also affects heme synthesis beyond metabolic steps involving ALA, leading to the
accumulation of protoporphyrin in erythrocytes as the result of impaired iron insertion into
the porphyrin moiety to form heme. The porphyrin acquires a zinc ion in lieu of the native
iron, and the resulting accumulation of blood zinc protoporphyrin (ZPP) tightly bound to ery-
throcytes for their entire life (120 days) represents a commonly employed index of lead-
CHPD1/A 1-143 9/30/83
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PRELIMINARY DRAFT
exposure for medical screening purposes. The threshold for elevation of erythrocyte protopor-
phyrin (EP) levels is well-established as being 25 to 30 ug/dl in adults and approximately 15
ug/dl for young children, with significant EP elevations (>1 to 2 standard deviations above
reference normal EP mean levels) occurring in 50 percent of all children studied as blood-lead
levels approach or moderately exceed 30 pg/dl.
Medically, small increases in EP levels have generally not been viewed as being of great
concern at initial detection levels around 15 to 20 ug/dl in children, but EP increases become
more worrisome as markedly greater, significant EP elevations occur as blood-lead levels
approach and exceed 30 ug/dl and additional signs of significantly deranged heme synthesis
begin to appear along with indications of functional disruption of various organ systems.
Previously, such other signs of significant organ system functional disruptions had only been
credibly detected at blood-lead levels somewhat in excess of 30 ug/dl, e.g., hemoglobin syn-
thesis inhibition starting at 40 ug/dl and significant nervous system effects at 50-60 ug/dl.
This served as a basis for CDC establishment of 30 ug/dl blood-lead as a criteria level for
undue lead exposure for young children and adoption by EPA of it as the "maximum safe" blood-
lead level (allowing some margin.of safety before reaching levels associated with inhibition
of hemoglobin synthesis or nervous system deficits) in setting the 1978 NAAQS for lead.
To the extent that new evidence is now available, indicative of probable lead effects on
nervous system functioning or other important physiological processes at blood-lead levels
below 30 to 40 ug/dl, then the rationale for continuing to view 30 pg/dl as a "maximum safe"
blood-lead level is called into question and substantial impetus is provided for revising the
criteria level downward, i.e., to some blood-lead level below 30 ug/dl. At this time, such
impetus toward revising the blood-lead criteria level downward is gaining momentum not only
from new neuropsychologic and electrophysiological findings of the type summarized above, but
also from growing evidence for lead effects on other functional systems. These include, for
example, the: (1) disruption of formation of the heme-containing protein, cytochrome c, of
considerable importance in cellular energetics involved in mediation of the normal functioning
of many different mammalian (including human) organ systems and tissues; (2) inhibition by
lead of the biosynthesis of globin, the protein moiety of hemoglobin, in the presense of lead
at concentrations corresponding to a blood-lead level of 20 ug/dl; (3) observations of signi-
ficant inhibition of pyrimidine-5'-nucleotidase (Py-5-N) activity in adults at blood-lead
levels Ł44 ug/dl and in children down to blood-lead levels of 10 ug/dl; and (4) observations
of lead interference with vitamin D metabolism in children across a blood-lead level range of
33 to 120 M9/dl, with consequent increasingly enhanced lead uptake due to decreased vitamin D
metabolism and likely associated increasingly cascading effects on nervous system and other
functions at sequentially higher blood-lead levels. Certain additional evidence for lead ef-
fects on hormonal systems and immune system components, thus far detected only at relatively
CHPD1/A 1-144 9/30/83
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PRELIMINARY DRAFT
high blood-lead levels or at least not credibly associated with blood-lead levels as low as 30
to 40 (jg/dl, also contributes to concern as blood-lead levels exceed 30 ug/dl.
Also adding to the concern about relatively low lead exposure levels are the results of
an expanding array of animal toxicology studies which demonstrate: (1) persistence of lead-
induced neurobehavioral alterations well into adulthood long after termination of perinatal
lead exposure early in development of several mammalian species; (2) evidence for uptake and
retention of lead in neural and non-neuronal elements of the CNS, including long-term persis-
tence in brain tissues after termination of external le.ad exposure and blood lead levels
return to "normal"; and (3) evidence from various in-vivo and in-vitro studies indicating
that, at least on a subcellular-molecular level, no threshold may exist for certain neurochem-
ical effects of lead.
1.13.5 DOSE-RESPONSE RELATIONSHIPS FOR LEAD EFFECTS IN HUMAN POPULATIONS
Information summarized in the preceding section dealt with the various biological effects
of lead germane to the general population and included comments about the various levels of
blood lead observed to be associated with the measurable onset of these effects in various
populations groups.
A number of investigators have attempted to quantify more precisely dose-population
response relationships for some of the above lead effects in human populations. That is they
have attempted to define the proportion of a population exhibiting a particular effect at a
given blood lead level. To date, such efforts at defining dose-response relationships for
lead effects have been mainly limited to the following effects of lead on heme biosynthesis:
inhibition of ALA-D activity; elevation of EP; and urinary excretion of ALA.
Dose-population response relationships for EP in children has been analyzed in detail by
Piomelli and et al. (1982) and the corresponding plot at 2 levels of elevation (>1 S.D., >2
S.D.) is shown in Figure 1-19 using probit analysis. It can be seen that blood lead levels in
half of the children showing EP elevations at >1 and 2 S.D.'s closely bracket the blood lead
level taken as the high end of "normal" (i.e., 30 ug/dl). Dose-response curves for adult men
and women as well as children prepared by Roels et al. (1976) are set forth in Figure 1-20.
In Figure 1-20, it may be seen that the dose-response for children remains greater across the
blood-lead range studied, followed by women, then adult males.
Figure 1-21 presents dose-population response data for urinary ALA exceeding two levels
(at mean + 1 S.D. and mean + 2 S.D.), as calculated by EPA from the data of Azar et at.
(1975). The percentages of the study populations exceeding the corresponding cut-off levels
as calculated by EPA for the Azar data are set forth in Table 1-21. It should be noted that
the measurement of ALA in the Azar et al. study did not account for amino acetone, which may
influence the results observed at the lowest blood lead levels.
CHP01/A 1-145 9/30/83
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PRELIMINARY DRAFT
10
20 30 40
BLOOD LEAD,
Figure 1-19. Dose-response for elevation of EP as a
function of blood lead level using probit analysis .
Geometric mean plus 1 S.D. = 33 /ug/dl; geometric mean
plus 2 S.D. = 53
Source: Piomelli et al. (1982).
CHPD1/A
100
80
A
a.
ffi
I 60
O
!•
o
ui
O
K
20
rep
ADULT FEMALES
ADULT MALES
10
20
30
40
60
BLOOD LEAD LEVEL, a Pb/dl
Figure 1-20. Dose-response curve for FEP as a function
of blood lead level: in subpopulations.
Source: Roels et al. (1976).
1-146
9/30/83
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PRELIMINARY DRAFT
100
90
80
70
60
2 50
2
(9
40
30
20
10
I I I I I I I I
O MEAN + 1 S.D.
A MEAN + 2 S.D.
MEAN ALAU = 0.32 FOR
BLOOD LEAD < 13 Mg/dl
10 20 30 40 SO 60 70
BLOOD LEAD LEVEL, M9 Pb/dl
80 90
Figure 1 -21. EPA calculated dose-response curve for
ALA-U.
Source: Azar et al. (1975).
TABLE 1-21. ERA-ESTIMATED PERCENTAGE OF SUBJECTS
WITH ALA-U EXCEEDING LIMITS FOR VARIOUS BLOOD LEAD LEVELS
Blood lead levels
10
20
30
40
50
60
70
Azar et al. (1975)
(Percent Population)
2
6
16
31
50
69
84
CHPD1/A
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PRELIMINARY DRAFT
1.13.6 POPULATIONS AT RISK
Population at risk is a segment of a defined population exhibiting characteristics asso-
ciated with significantly higher probability of developing a condition, illness, or other ab-
normal status. This high risk may result from either (1) greater inherent susceptibility or
(2) from exposure situations peculiar to that group. What is meant by inherent susceptibility
is a host characteristic or status that predisposes the host to a greater risk of heightened
response to an external stimulus or agent.
In regard to lead, two such populations are definable. They are preschool age children,
especially those living in urban settings, and pregnant women, the latter group owing mainly
to the risk to the conceptus. Children are such a population for both of the reasons stated
above, whereas pregnant women are at risk primarily due to the inherent susceptibility of the
conceptus.
1.13.6.1 Children as a Population at Risk. Children are developing and growing organisms ex-
hibiting certain differences from adults in terms of basic physiologic mechanisms, capability
of coping with physiologic stress, and their relative metabolism of lead. Also, the behavior
of children frequently places them in different relationship to sources of lead in the envi-
ronment, thereby enhancing the opportunity for them to absorb lead. Furthermore, the occur-
rence of excessive exposure often is not realized until serious harm is done. Young children
do not readily communicate a medical history of lead exposure, the early signs of such being
common to so many other disease states that lead is frequently not recognized early on as a
possible etiological factor contributing to the manifestation of other symptoms.
Inherent Susceptibility of the Young. Discussion of the physiological vulnerability of
the young must address two discrete areas. Not only should the basic physiological differ-
ences be considered that one would expect to predispose children to a heightened vulnerability
to lead, but also the actual clinical evidence must be considered that shows such vulnerabil-
ity does indeed exist.
In Chapter 10 and Section 1.13.2 above, differences in relative exposure to lead and body
handling of lead for children versus adults were pinpointed throughout the text. The signifi-
cant elements of difference include: (1) greater intake of lead by infants and young children
into the respiratory and gastro-intestinal tracts on a body weight basis compared to adults;
(2) greater absorption and retention rates of lead in children; (3) much greater prevalence of
nutrient deficiency in the case of nutrients which affect lead absorption rates from the GI
tract; (4) differences in certain habits, i.e., normal hand to mouth activity as well as pica
resulting in the transfer of lead-contaminated dust and dirt to the GI tract; (5) differences
in the efficiency of lead sequestration in the bones of children, such that not only is less
of the body burden of lead in bone at any given time but the amount present may be relatively
more labile. Additional information discussed in Chapter 12 suggests that the blood-brain
CHPD1/A 1-148 9/30/83
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PRELIMINARY DRAFT
barrier in children is less developed, posing the risk for greater entry of lead into the
nervous system.
Hematological and neurological effects in children have been demonstrated to have lower
thresholds in terms of blood lead levels than in adults. The extent of reduced hemoglobin
production and EP accumulation occur at relatively lower exposure levels in children than in
adults, as indexed by blood lead thresholds. With reference to neurologic effects, the onset
of encephalopathy and other injury to the nervous system appears to vary both regarding likely
lower thresholds in children for some effects and in the typical pattern of neurologic effects
presented, e.g. , in encephalopathy or other CNS deficits being more common in children versus
peripheral neuropathy being more often seen in adults. Not only are the effects more acute in
children than in adults, but also the neurologic sequelae are usually much more severe in
children.
Exposure Consideration. The dietary habits of children as well as the diets themselves
differ markedly from adults and, as a result, place children in a different relationship to
several sources of lead. The dominance of canned milk and processed baby food in the diet of
many young children is an important factor in assessing their exposure to lead since both
those foodstuffs have been shown to contain higher amounts of lead than components of the
adult diet. The importance of these lead sources is not their relationship to airborne lead
directly but, rather, their role in providing a higher baseline lead burden to which the air-
borne contribution is added.
Children ordinarily undergo a stage of development in which they exhibit normal mouthing
behavior, as manifested, for example, in the form of thumbsucking. At this time they are at
risk for picking up lead-contaminated soil and dust on their hands and hence into their mouths
where it can be absorbed. Scientific evidence documenting at least the first part of the
chain is available.
There is, however, an abnormal extension of mouthing behavior, called pica, which occurs
in some children. Although diagnosis of this is difficult, children who exhibit this trait
have been shown to purposefully eat nonfood items. Much of the lead-based paint problem is
known to occur because children actively ingest chips, of leaded paint.
1.13.6.2 Pregnant Women and the Conceptus as a Population at Risk. There are some rather in-
conculsive data indicating that women may in general be somewhat higher risk to lead than men.
However, pregnant women and their concept! as a subgroup are demonstrably at higher risk. It
should be pointed out that, in fact, it really is not the pregnant woman per se who is at
greatest risk but, rather, the unborn child she is carrying. Because of obstetric complica-
tions, however, the mother herself can also be at somewhat greater risk at the time of deliv-
ery of her child.
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Studies have demonstrated that women in general, like children, tend to show a heightened
response of erythorcyte protoporphyrin levels upon exposure to lead. The exact reason for
this heightened response is not known but may relate to endocrine differences between men and
women.
As stated above, the primary reason pregnant women are a high-risk group is because of
the fetus each is carrying. In addition, there is some suggestive evidence that lead expo-
sures may also affect maternal complications at delivery. With reference to maternal compli-
cation at delivery, information in the literature suggests that the incidence of preterm deli-
very and premature membrane rupture relates to maternal blood lead level. Further study of
this relationship as well as studies relating to discrete health effects in the newborn are
needed.
Vulnerability of the developing fetus to lead exposure arising from transplacental trans-
fer of maternal lead was discussed in Chapter 10. This process starts at the end of the first
trimester. Umbilical cord blood studies involving mother-infant pairs have repeatedly shown a
correlation between maternal and fetal blood lead levels.
Further suggestive evidence, cited in Chapter 12, has been advanced for prenatal lead
exposures of fetuses possibly leading to later higher instances of postnatal mental retarda-
tion among the affected offspring. The available data are insufficient to state with any cer-
tainty that such effects occur or to determine with any precision what levels of lead exposure
might be required prior to or during pregnancy in order to produce such effects.
1.13.6.3 Description of the United States Population in Relation to Potential Lead Exposure
Risk
In this section, estimates are provided of the number of individuals in those segments of
the population which have been defined as being potentially at greatest risk for lead ex-
posures. These segments include pre-school children (up to 6 years of age), especially those
living in urban settings, and women of child-bearing age (defined here as ages 15-44). These
data, which are presented below in Table 1-22, were obtained from a provisional report by the
U.S. Census Bureau (1982), which indicates that approximately 61 percent of the populace lives
in urban areas (defined as central cities and urban fringe). Assuming that the 61 percent
estimate for urban residents also applies to children of preschool age, then approximately
14,206,000 children of the total listed in Table 1-22 would be expected to be at greater risk
by virtue of higher lead exposures generally associated with their living in urban versus non-
urban settings. (NOTE: The age distribution of the percentage of urban residents may vary
between SMSA's.)
The risk encountered with exposure to lead may be compounded by nutritional deficits (see
Chapter 10). The most commonly seen of these is iron deficiency, especially in young children
less than 5 years of age (Mahaffey and Michaelson, 1980). Data available from, the National
CHPD1/A 1-150 9/30/83
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TABLE 1-22. PROVISIONAL ESTIMATE OF THE NUMBER OF INDIVIDUALS IN URBAN AND
RURAL POPULATION SEGMENTS AT GREATEST POTENTIAL RISK TO LEAD EXPOSURE
Population Segment
Pre-school children
Total
Women of
child-bearing age
Total
Actual Age
(year)
0-4
5
6
15-19
20-24
25-29
30-34
35-39
40-44
Total Number in U.S.
Population
(1981)
16,939,000
3,201,000
3,147,000
23,287,000
10,015,000
10,818,000
10,072,000
9,463,000
7,320,000
6,147,000
53,835,000
Urban
Population1
10,333,000
1,953,000
1,920,000
14,206,000
6,109,000
6,599,000
6,144,000
5,772,000
4,465,000
3,749,000
32,838,000
Source: U.S. Census Bureau (1982), Tables 18 and 31.
*An urban/total ratio of 0.61 was used for all age groups. "Urban" includes central city
and urban fringe populations.
Center for Health Statistics for 1976-1980 (Fulwood et al., 1982) indicate that from 8 to 22
percent of children aged 3-5 may exhibit iron deficiency, depending upon whether this condi-
tion is defined as serum iron concentration (<40 ug/dl) or as transferrin saturation (<16 per-
cent), respectively. Hence, of the 20,140,000 children g5 years of age (Table 1-22), as many
as 4,431,000 would be expected to be at increased risk depending on their exposure to lead,
due to iron deficiency.
As pointed out in Section 1.13.7, the risk to pregnant women is mainly due to risk to the
conceptus. By dividing the total number of women of child-bearing age in 1981 (53,835,000)
into the total number of live births in 1981 (3,646,000; National Center for Health Statis-
tics, 1982), it may be seen that approximately 7 percent of this segment of the population
may be at increased risk at any given time.
1.13.7 SUMMARY AND CONCLUSIONS
Among the most significant pieces of information and conclusions that emerge from the
present human health risk evaluation are the following:
(1) Anthropogenic activity has clearly led to vast increases of lead input into those en-
vironmental compartments which serve as media (e.g., air, water, food, etc.) by which
significant human exposure to lead occurs.
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(2) Emission of lead into the atmosphere, especially through leaded gasoline combustion, is
of major significance in terms of both the movement of lead to other environmental com-
partments and the relative impact of such emissions on the internal lead burdens in in-
dustrialized human populations. By means of both mathematical modeling of available
clinical/epidemiological data by EPA and the isotopic tracrng of lead from gasoline to
the atmosphere to human blood of exposed populations, the size of atmospheric lead con-
tribution can be confidently said to be 25-50 percent or, probably somewhat higher.
(3) Given this magnitude of relative contribution to human external and internal exposure,
reduction in levels of atmospheric lead would then result in significant widespread
reductions in levels of lead in human blood (an outcome which is supported by careful
analysis of the NHANES II study data). Reduction of lead in food (added in the course of
harvesting, transport, and processing) would also be expected to produce significant
widespread reductions in human blood lead levels in the United States.
(4) A number of adverse effects in humans and other species are clearly associated with lead
exposure and, from a historical perspective, the observed "thresholds" for these various
effects (particularly neurological and heme biosynthesis effects) continue to decline as
more sophisticated experimental and clinical measures are employed to detect more subtle,
but still significant effects. These include significant alterations in normal physio-
logical functions at blood lead levels markedly below the currently accepted 30 ug/dl
"maxim safe level" for pediatric exposures.
(5) Several chapters of this document demonstrate that young children are at greatest risk
for experiencing lead-induced health effects, particularly in the urbanized, low income
segments of this pediatric population. A second group at increased risk are pregnant
women, because of exposure of the fetus to lead in the absence of any effective biologi-
cal (e.g. placental) barrier during gestation.
(6) Dose-population response information for heme synthesis effects, coupled with information
from various blood lead surveys, e.g. the NHANES II study, indicate that large numbers of
American children (especially low income, urban dwellers) have blood lead levels suffi-
ciently high (in excess of 15-20 ug/dl) that they are clearly at risk for deranged heme
synthesis and, possibly, other health effects of growing concern as lead's role as a
general systemic toxicant becomes more fully understood.
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